ID APAF_HUMAN Reviewed; 1248 AA. AC O14727; B2RMX8; O43297; Q7Z438; Q9BXZ6; Q9UBZ5; Q9UGN8; Q9UGN9; AC Q9UGP0; Q9UJ58; Q9UJ59; Q9UJ60; Q9UJ61; Q9UJ62; Q9UJ63; Q9UJ64; AC Q9UJ65; Q9UJ66; Q9UJ67; Q9UNC9; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2002, sequence version 2. DT 18-JUL-2018, entry version 210. DE RecName: Full=Apoptotic protease-activating factor 1; DE Short=APAF-1; GN Name=APAF1; Synonyms=KIAA0413; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND PARTIAL PROTEIN SEQUENCE. RC TISSUE=Cervix carcinoma; RX PubMed=9267021; DOI=10.1016/S0092-8674(00)80501-2; RA Zou H., Henzel W.J., Liu X., Lutschg A., Wang X.; RT "Apaf-1, a human protein homologous to C. elegans CED-4, participates RT in cytochrome c-dependent activation of caspase-3."; RL Cell 90:405-413(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 4 AND 5). RC TISSUE=Cervix carcinoma, Heart, and Peripheral blood; RX PubMed=10441496; DOI=10.1006/bbrc.1999.1124; RA Hahn C., Hirsch B., Jahnke D., Duerkop H., Stein H.; RT "Three new types of Apaf-1 in mammalian cells."; RL Biochem. Biophys. Res. Commun. 261:746-749(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=T-cell; RX PubMed=10364241; DOI=10.1074/jbc.274.25.17941; RA Saleh A., Srinivasula S.M., Acharya S., Fishel R., Alnemri E.S.; RT "Cytochrome c and dATP-mediated oligomerization of Apaf-1 is a RT prerequisite for procaspase-9 activation."; RL J. Biol. Chem. 274:17941-17945(1999). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBUNIT, AND RP MUTAGENESIS OF LYS-160 AND MET-368. RC TISSUE=Kidney; RX PubMed=10393175; DOI=10.1093/emboj/18.13.3586; RA Hu Y., Benedict M.A., Ding L., Nunez G.; RT "Role of cytochrome c and dATP/ATP hydrolysis in Apaf-1-mediated RT caspase-9 activation and apoptosis."; RL EMBO J. 18:3586-3595(1999). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 6), FUNCTION, AND RP SUBCELLULAR LOCATION. RC TISSUE=Prostatic carcinoma; RX PubMed=12804598; DOI=10.1016/S0006-291X(03)00995-1; RA Ogawa T., Shiga K., Hashimoto S., Kobayashi T., Horii A., Furukawa T.; RT "APAF-1-ALT, a novel alternative splicing form of APAF-1, potentially RT causes impeded ability of undergoing DNA damage-induced apoptosis in RT the LNCaP human prostate cancer cell line."; RL Biochem. Biophys. Res. Commun. 306:537-543(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=9455477; DOI=10.1093/dnares/4.5.307; RA Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N., RA Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. VIII. RT 78 new cDNA clones from brain which code for large proteins in RT vitro."; RL DNA Res. 4:307-313(1997). RN [7] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 810-864 AND 866-883. RA Roberts D.L., Dalgleish R., Cohen G.M., MacFarlane M.; RT "The mammalian CED4 homologue, APAF1, exists as two distinct forms in RT human cells."; RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-138 (ISOFORMS 1/4/5). RA Won M., Lee J.-W., Ohr H.-H., Kim D.-U., Chung K.-S., Lee M., RA Yoo H.-S.; RT "Cloning of variant Apaf1."; RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases. RN [12] RP APAF-1-MEDIATED OLIGOMERIZATION. RX PubMed=9651578; DOI=10.1016/S1097-2765(00)80095-7; RA Srinivasula S.M., Ahmad M., Fernandes-Alnemri T., Alnemri E.S.; RT "Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization."; RL Mol. Cell 1:949-957(1998). RN [13] RP INDUCTION BY E2F AND TP53. RX PubMed=11389439; DOI=10.1038/35078527; RA Moroni M.C., Hickman E.S., Denchi E.L., Caprara G., Colli E., RA Cecconi F., Mueller H., Helin K.; RT "Apaf-1 is a transcriptional target for E2F and p53."; RL Nat. Cell Biol. 3:552-558(2001). RN [14] RP INTERACTION WITH APIP. RX PubMed=15262985; DOI=10.1074/jbc.M405747200; RA Cho D.-H., Hong Y.-M., Lee H.-J., Woo H.-N., Pyo J.-O., Mak T.W., RA Jung Y.-K.; RT "Induced inhibition of ischemic/hypoxic injury by APIP, a novel Apaf- RT 1-interacting protein."; RL J. Biol. Chem. 279:39942-39950(2004). RN [15] RP INHIBITION BY CALCIUM. RX PubMed=17244527; DOI=10.1016/j.molcel.2006.12.013; RA Bao Q., Lu W., Rabinowitz J.D., Shi Y.; RT "Calcium blocks formation of apoptosome by preventing nucleotide RT exchange in Apaf-1."; RL Mol. Cell 25:181-192(2007). RN [16] RP INTERACTION WITH NAIP/BIRC1. RX PubMed=21371431; DOI=10.1016/j.bbrc.2011.02.130; RA Karimpour S., Davoodi J., Ghahremani M.H.; RT "Integrity of ATP binding site is essential for effective inhibition RT of the intrinsic apoptosis pathway by NAIP."; RL Biochem. Biophys. Res. Commun. 407:158-162(2011). RN [17] RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 1-97. RX PubMed=10543941; DOI=10.1006/jmbi.1999.3177; RA Vaughn D.E., Rodriguez J., Lazebnik Y., Joshua-Tor L.; RT "Crystal structure of Apaf-1 caspase recruitment domain: an alpha- RT helical Greek key fold for apoptotic signaling."; RL J. Mol. Biol. 293:439-447(1999). RN [18] RP STRUCTURE BY NMR OF 1-97. RX PubMed=10578182; DOI=10.1038/sj.cdd.4400584; RA Day C.L., Dupont C., Lackmann M., Vaux D.L., Hinds M.G.; RT "Solution structure and mutagenesis of the caspase recruitment domain RT (CARD) from Apaf-1."; RL Cell Death Differ. 6:1125-1132(1999). CC -!- FUNCTION: Oligomeric Apaf-1 mediates the cytochrome c-dependent CC autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the CC activation of caspase-3 and apoptosis. This activation requires CC ATP. Isoform 6 is less effective in inducing apoptosis. CC {ECO:0000269|PubMed:10393175, ECO:0000269|PubMed:12804598}. CC -!- SUBUNIT: Monomer. Oligomerizes to a heptameric ring, known as the CC apoptosome, upon binding of cytochrome c and dATP. Oligomeric CC Apaf-1 and pro-caspase-9 bind to each other via their respective CC NH2-terminal CARD domains and consecutively mature caspase-9 is CC released from the complex. Pro-caspase-3 is recruited into the CC Apaf-1-pro-caspase-9 complex via interaction with pro-caspase-9. CC Interacts with APIP. Interacts (via CARD and NACHT domains) with CC NAIP/BIRC1 (via NACHT domain). {ECO:0000269|PubMed:10393175, CC ECO:0000269|PubMed:15262985, ECO:0000269|PubMed:21371431}. CC -!- INTERACTION: CC Q9NQS1:AVEN; NbExp=2; IntAct=EBI-446492, EBI-7370203; CC Q9Z0F3:Bcl2l10 (xeno); NbExp=2; IntAct=EBI-446492, EBI-8658693; CC P42574:CASP3; NbExp=7; IntAct=EBI-446492, EBI-524064; CC P55211:CASP9; NbExp=25; IntAct=EBI-446492, EBI-516799; CC P99999:CYCS; NbExp=6; IntAct=EBI-446492, EBI-446479; CC P08107:HSPA1B; NbExp=2; IntAct=EBI-446492, EBI-629985; CC P62136:PPP1CA; NbExp=2; IntAct=EBI-446492, EBI-357253; CC P62258:YWHAE; NbExp=2; IntAct=EBI-446492, EBI-356498; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12804598}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=1; Synonyms=Apaf-1XL; CC IsoId=O14727-1; Sequence=Displayed; CC Name=2; Synonyms=Apaf-1L; CC IsoId=O14727-2; Sequence=VSP_006759; CC Name=3; Synonyms=Apaf-1S; CC IsoId=O14727-3; Sequence=VSP_006759, VSP_006761; CC Name=4; Synonyms=Apaf-1M; CC IsoId=O14727-4; Sequence=VSP_006761; CC Name=5; Synonyms=Apaf-1XS; CC IsoId=O14727-5; Sequence=VSP_006760, VSP_006761, VSP_006762; CC Name=6; Synonyms=Apaf-1-ALT; CC IsoId=O14727-6; Sequence=VSP_008965, VSP_008966; CC -!- TISSUE SPECIFICITY: Ubiquitous. Highest levels of expression in CC adult spleen and peripheral blood leukocytes, and in fetal brain, CC kidney and lung. Isoform 1 is expressed in heart, kidney and CC liver. CC -!- INDUCTION: By E2F and p53/TP53 in apoptotic neurons. CC {ECO:0000269|PubMed:11389439}. CC -!- DOMAIN: The CARD domain mediates interaction with APIP. CC -!- DOMAIN: The monomeric form is autoinhibited in a closed CC conformation through a bound ADP at the nucleotide binding site. CC Exchange of ADP for ATP and binding of cytochrome c trigger a CC large conformational change where the first WD repeat region CC swings out, allowing the NB-ARC domain to rotate and expose the CC contact areas for oligomerization (By similarity). {ECO:0000250}. CC -!- MISCELLANEOUS: Physiological concentrations of calcium ions CC negatively affect the assembly of apoptosome by inhibiting CC nucleotide exchange in the monomeric form. CC -!- SEQUENCE CAUTION: CC Sequence=AAK28401.1; Type=Frameshift; Positions=108; Evidence={ECO:0000305}; CC Sequence=BAA24843.2; Type=Erroneous initiation; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/APAF1ID422.html"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AF013263; AAC51678.1; -; mRNA. DR EMBL; AJ243003; CAB55579.1; -; mRNA. DR EMBL; AJ243004; CAB55580.1; -; mRNA. DR EMBL; AJ243005; CAB55581.1; -; mRNA. DR EMBL; AJ243006; CAB55582.1; -; mRNA. DR EMBL; AJ243007; CAB55583.1; -; mRNA. DR EMBL; AJ243008; CAB55584.1; -; mRNA. DR EMBL; AJ243009; CAB55585.1; -; mRNA. DR EMBL; AJ243010; CAB55586.1; -; mRNA. DR EMBL; AJ243011; CAB55587.1; -; mRNA. DR EMBL; AJ243048; CAB55588.1; -; mRNA. DR EMBL; AJ243107; CAB56462.1; -; mRNA. DR EMBL; AF134397; AAD38344.1; -; mRNA. DR EMBL; AF149794; AAD34016.1; -; mRNA. DR EMBL; AB007873; BAA24843.2; ALT_INIT; mRNA. DR EMBL; AB103079; BAC77343.1; -; mRNA. DR EMBL; CH471054; EAW97606.1; -; Genomic_DNA. DR EMBL; BC136531; AAI36532.1; -; mRNA. DR EMBL; BC136532; AAI36533.1; -; mRNA. DR EMBL; AJ133643; CAB65085.1; -; Genomic_DNA. DR EMBL; AJ133644; CAB65086.1; -; Genomic_DNA. DR EMBL; AJ133645; CAB65087.1; -; Genomic_DNA. DR EMBL; AF248734; AAK28401.1; ALT_FRAME; mRNA. DR CCDS; CCDS55862.1; -. [O14727-2] DR CCDS; CCDS55863.1; -. [O14727-3] DR CCDS; CCDS9069.1; -. [O14727-1] DR CCDS; CCDS9070.1; -. [O14727-4] DR CCDS; CCDS9071.1; -. [O14727-6] DR PIR; T03818; T03818. DR RefSeq; NP_001151.1; NM_001160.2. [O14727-3] DR RefSeq; NP_037361.1; NM_013229.2. [O14727-2] DR RefSeq; NP_863651.1; NM_181861.1. [O14727-1] DR RefSeq; NP_863658.1; NM_181868.1. [O14727-4] DR RefSeq; NP_863659.1; NM_181869.1. [O14727-6] DR UniGene; Hs.552567; -. DR PDB; 1C15; NMR; -; A=1-97. DR PDB; 1CWW; NMR; -; A=1-97. DR PDB; 1CY5; X-ray; 1.30 A; A=1-97. DR PDB; 1Z6T; X-ray; 2.21 A; A/B/C/D=1-591. DR PDB; 2P1H; X-ray; 1.59 A; A=1-92. DR PDB; 2YGS; X-ray; 1.60 A; A=1-92. DR PDB; 3J2T; EM; 9.5 A; A/B/C/D/E/F/G=1-1248. DR PDB; 3JBT; EM; 3.80 A; A/C/E/G/I/K/M=1-1248. DR PDB; 3YGS; X-ray; 2.50 A; C=1-95. DR PDB; 4RHW; X-ray; 2.10 A; A/B/C/D=1-97. DR PDB; 5JUY; EM; 4.10 A; A/B/C/D/E/F/G=1-1248. DR PDB; 5WVC; X-ray; 2.99 A; A/C/E=1-95. DR PDB; 5WVE; EM; 4.40 A; A/C/E/G/I/K/M=1-1248, O/P/Q/R/W/X=1-102. DR PDBsum; 1C15; -. DR PDBsum; 1CWW; -. DR PDBsum; 1CY5; -. DR PDBsum; 1Z6T; -. DR PDBsum; 2P1H; -. DR PDBsum; 2YGS; -. DR PDBsum; 3J2T; -. DR PDBsum; 3JBT; -. DR PDBsum; 3YGS; -. DR PDBsum; 4RHW; -. DR PDBsum; 5JUY; -. DR PDBsum; 5WVC; -. DR PDBsum; 5WVE; -. DR ProteinModelPortal; O14727; -. DR SMR; O14727; -. DR BioGrid; 106814; 30. DR CORUM; O14727; -. DR DIP; DIP-27624N; -. DR IntAct; O14727; 10. DR MINT; O14727; -. DR STRING; 9606.ENSP00000448165; -. DR BindingDB; O14727; -. DR ChEMBL; CHEMBL1795093; -. DR DrugBank; DB00171; Adenosine triphosphate. DR iPTMnet; O14727; -. DR PhosphoSitePlus; O14727; -. DR BioMuta; APAF1; -. DR EPD; O14727; -. DR MaxQB; O14727; -. DR PaxDb; O14727; -. DR PeptideAtlas; O14727; -. DR PRIDE; O14727; -. DR ProteomicsDB; 48182; -. DR ProteomicsDB; 48183; -. [O14727-2] DR ProteomicsDB; 48184; -. [O14727-3] DR ProteomicsDB; 48185; -. [O14727-4] DR ProteomicsDB; 48186; -. [O14727-5] DR ProteomicsDB; 48187; -. [O14727-6] DR Ensembl; ENST00000333991; ENSP00000334558; ENSG00000120868. [O14727-6] DR Ensembl; ENST00000357310; ENSP00000349862; ENSG00000120868. [O14727-4] DR Ensembl; ENST00000359972; ENSP00000353059; ENSG00000120868. [O14727-3] DR Ensembl; ENST00000547045; ENSP00000449791; ENSG00000120868. [O14727-4] DR Ensembl; ENST00000550527; ENSP00000448449; ENSG00000120868. [O14727-2] DR Ensembl; ENST00000551964; ENSP00000448165; ENSG00000120868. [O14727-1] DR Ensembl; ENST00000552268; ENSP00000448826; ENSG00000120868. [O14727-6] DR GeneID; 317; -. DR KEGG; hsa:317; -. DR UCSC; uc001tfz.4; human. [O14727-1] DR CTD; 317; -. DR DisGeNET; 317; -. DR EuPathDB; HostDB:ENSG00000120868.13; -. DR GeneCards; APAF1; -. DR HGNC; HGNC:576; APAF1. DR HPA; CAB069399; -. DR HPA; HPA031373; -. DR MIM; 602233; gene. DR neXtProt; NX_O14727; -. DR OpenTargets; ENSG00000120868; -. DR PharmGKB; PA24868; -. DR eggNOG; KOG4155; Eukaryota. DR eggNOG; KOG4658; Eukaryota. DR eggNOG; ENOG410XP3K; LUCA. DR GeneTree; ENSGT00920000149054; -. DR HOVERGEN; HBG018730; -. DR InParanoid; O14727; -. DR KO; K02084; -. DR OMA; SVNHCRF; -. DR OrthoDB; EOG091G036U; -. DR PhylomeDB; O14727; -. DR TreeFam; TF323866; -. DR Reactome; R-HSA-111458; Formation of apoptosome. DR Reactome; R-HSA-111459; Activation of caspases through apoptosome-mediated cleavage. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-6803207; TP53 Regulates Transcription of Caspase Activators and Caspases. DR Reactome; R-HSA-8953750; Transcriptional Regulation by E2F6. DR SABIO-RK; O14727; -. DR SignaLink; O14727; -. DR SIGNOR; O14727; -. DR EvolutionaryTrace; O14727; -. DR GeneWiki; APAF1; -. DR GenomeRNAi; 317; -. DR PMAP-CutDB; O14727; -. DR PRO; PR:O14727; -. DR Proteomes; UP000005640; Chromosome 12. DR Bgee; ENSG00000120868; -. DR ExpressionAtlas; O14727; baseline and differential. DR Genevisible; O14727; HS. DR GO; GO:0043293; C:apoptosome; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IEA:Ensembl. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome. DR GO; GO:0043531; F:ADP binding; IEA:InterPro. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; IBA:GO_Central. DR GO; GO:0031072; F:heat shock protein binding; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl. DR GO; GO:0000166; F:nucleotide binding; TAS:UniProtKB. DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0008635; P:activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c; IDA:UniProtKB. DR GO; GO:0007568; P:aging; IEA:Ensembl. DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc. DR GO; GO:0010659; P:cardiac muscle cell apoptotic process; IEA:Ensembl. DR GO; GO:0030154; P:cell differentiation; IEA:Ensembl. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl. DR GO; GO:0030900; P:forebrain development; IEA:Ensembl. DR GO; GO:0034349; P:glial cell apoptotic process; IEA:Ensembl. DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:UniProtKB. DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IEA:Ensembl. DR GO; GO:0070317; P:negative regulation of G0 to G1 transition; TAS:Reactome. DR GO; GO:0007399; P:nervous system development; TAS:ProtInc. DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl. DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl. DR GO; GO:0043312; P:neutrophil degranulation; TAS:Reactome. DR GO; GO:0043065; P:positive regulation of apoptotic process; TAS:UniProtKB. DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0051260; P:protein homooligomerization; IEA:Ensembl. DR GO; GO:1902510; P:regulation of apoptotic DNA fragmentation; IEA:Ensembl. DR GO; GO:0042981; P:regulation of apoptotic process; TAS:UniProtKB. DR GO; GO:0072432; P:response to G1 DNA damage checkpoint signaling; TAS:UniProtKB. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl. DR CDD; cd08323; CARD_APAF1; 1. DR Gene3D; 1.10.10.10; -; 1. DR Gene3D; 2.130.10.10; -; 3. DR InterPro; IPR017251; Apaf-1. DR InterPro; IPR037963; APAF1_CARD_dom. DR InterPro; IPR001315; CARD. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR020472; G-protein_beta_WD-40_rep. DR InterPro; IPR002182; NB-ARC. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR001680; WD40_repeat. DR InterPro; IPR019775; WD40_repeat_CS. DR InterPro; IPR017986; WD40_repeat_dom. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR InterPro; IPR036388; WH-like_DNA-bd_sf. DR Pfam; PF00619; CARD; 1. DR Pfam; PF00931; NB-ARC; 1. DR Pfam; PF00400; WD40; 9. DR PIRSF; PIRSF037646; Apop_pept_activating-1; 1. DR PRINTS; PR00320; GPROTEINBRPT. DR SMART; SM00320; WD40; 13. DR SUPFAM; SSF47986; SSF47986; 1. DR SUPFAM; SSF50978; SSF50978; 2. DR SUPFAM; SSF52540; SSF52540; 1. DR PROSITE; PS50209; CARD; 1. DR PROSITE; PS00678; WD_REPEATS_1; 4. DR PROSITE; PS50082; WD_REPEATS_2; 9. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; ATP-binding; Calcium; KW Complete proteome; Cytoplasm; Direct protein sequencing; KW Nucleotide-binding; Reference proteome; Repeat; WD repeat. FT CHAIN 1 1248 Apoptotic protease-activating factor 1. FT /FTId=PRO_0000050844. FT DOMAIN 1 90 CARD. {ECO:0000255|PROSITE- FT ProRule:PRU00046}. FT DOMAIN 104 415 NB-ARC. FT REPEAT 613 652 WD 1-1. FT REPEAT 655 694 WD 1-2. FT REPEAT 697 738 WD 1-3. FT REPEAT 741 780 WD 1-4. FT REPEAT 796 836 WD 1-5. FT REPEAT 838 877 WD 1-6. FT REPEAT 880 910 WD 1-7. FT REPEAT 922 958 WD 2-1. FT REPEAT 959 998 WD 2-2. FT REPEAT 1001 1040 WD 2-3. FT REPEAT 1042 1080 WD 2-4. FT REPEAT 1083 1122 WD 2-5. FT REPEAT 1125 1164 WD 2-6. FT REPEAT 1175 1212 WD 2-7. FT REPEAT 1213 1248 WD 2-8. FT NP_BIND 154 161 ATP. {ECO:0000255}. FT REGION 910 921 Interpropeller linker. {ECO:0000250}. FT COMPBIAS 95 98 Poly-Ser. FT BINDING 265 265 ATP. {ECO:0000250}. FT VAR_SEQ 99 109 Missing (in isoform 2 and isoform 3). FT {ECO:0000303|PubMed:10364241, FT ECO:0000303|PubMed:9267021, FT ECO:0000303|PubMed:9455477}. FT /FTId=VSP_006759. FT VAR_SEQ 319 338 GSPLVVSLIGALLRDFPNRW -> VVERCHWGILTDLLHKW FT NQS (in isoform 6). FT {ECO:0000303|PubMed:12804598}. FT /FTId=VSP_008965. FT VAR_SEQ 339 1248 Missing (in isoform 6). FT {ECO:0000303|PubMed:12804598}. FT /FTId=VSP_008966. FT VAR_SEQ 575 575 E -> ETLGFESKK (in isoform 5). FT {ECO:0000303|PubMed:10441496}. FT /FTId=VSP_006760. FT VAR_SEQ 824 866 Missing (in isoform 3, isoform 4 and FT isoform 5). {ECO:0000303|PubMed:10441496, FT ECO:0000303|PubMed:9267021}. FT /FTId=VSP_006761. FT VAR_SEQ 1113 1154 Missing (in isoform 5). FT {ECO:0000303|PubMed:10441496}. FT /FTId=VSP_006762. FT MUTAGEN 160 160 K->R: No association with APAF-1. No FT binding to pro-caspase-9. FT {ECO:0000269|PubMed:10393175}. FT MUTAGEN 368 368 M->L: Activation of pro-caspase-9 FT independent of cytochrome c. Increased FT ability to induce apoptosis. FT {ECO:0000269|PubMed:10393175}. FT CONFLICT 134 134 N -> S (in Ref. 11). {ECO:0000305}. FT CONFLICT 145 145 G -> C (in Ref. 2; CAB55587). FT {ECO:0000305}. FT CONFLICT 161 161 S -> F (in Ref. 2; CAB55586). FT {ECO:0000305}. FT CONFLICT 370 370 I -> T (in Ref. 2; CAB55581). FT {ECO:0000305}. FT CONFLICT 383 383 Y -> H (in Ref. 2; CAB55586). FT {ECO:0000305}. FT CONFLICT 544 544 F -> L (in Ref. 2; CAB55584). FT {ECO:0000305}. FT CONFLICT 580 580 A -> T (in Ref. 2; CAB55580). FT {ECO:0000305}. FT CONFLICT 608 608 R -> C (in Ref. 2; CAB55585). FT {ECO:0000305}. FT CONFLICT 620 620 H -> R (in Ref. 2; CAB55587). FT {ECO:0000305}. FT CONFLICT 639 639 L -> F (in Ref. 2; CAB55583). FT {ECO:0000305}. FT CONFLICT 708 708 T -> A (in Ref. 2; CAB55579). FT {ECO:0000305}. FT CONFLICT 742 742 H -> R (in Ref. 2; CAB55584). FT {ECO:0000305}. FT CONFLICT 746 746 V -> A (in Ref. 2; CAB55586). FT {ECO:0000305}. FT CONFLICT 757 757 L -> P (in Ref. 2; CAB56462). FT {ECO:0000305}. FT CONFLICT 795 795 E -> G (in Ref. 2; CAB55581). FT {ECO:0000305}. FT CONFLICT 798 798 E -> G (in Ref. 2; CAB55587). FT {ECO:0000305}. FT CONFLICT 825 825 D -> A (in Ref. 2; CAB55585). FT {ECO:0000305}. FT CONFLICT 871 871 S -> L (in Ref. 2; CAB55587). FT {ECO:0000305}. FT CONFLICT 876 876 A -> T (in Ref. 2; CAB55581). FT {ECO:0000305}. FT CONFLICT 949 949 I -> V (in Ref. 2; CAB55585). FT {ECO:0000305}. FT CONFLICT 1008 1008 H -> R (in Ref. 2; CAB55582). FT {ECO:0000305}. FT CONFLICT 1056 1056 S -> P (in Ref. 2; CAB55582). FT {ECO:0000305}. FT CONFLICT 1241 1241 L -> I (in Ref. 6; BAA24843). FT {ECO:0000305}. FT HELIX 3 11 {ECO:0000244|PDB:1CY5}. FT HELIX 13 19 {ECO:0000244|PDB:1CY5}. FT HELIX 22 32 {ECO:0000244|PDB:1CY5}. FT HELIX 37 44 {ECO:0000244|PDB:1CY5}. FT STRAND 46 48 {ECO:0000244|PDB:1CY5}. FT HELIX 49 61 {ECO:0000244|PDB:1CY5}. FT HELIX 65 77 {ECO:0000244|PDB:1CY5}. FT HELIX 81 87 {ECO:0000244|PDB:1CY5}. FT HELIX 88 90 {ECO:0000244|PDB:1CY5}. FT HELIX 99 104 {ECO:0000244|PDB:1Z6T}. FT HELIX 108 116 {ECO:0000244|PDB:1Z6T}. FT HELIX 130 140 {ECO:0000244|PDB:1Z6T}. FT STRAND 148 153 {ECO:0000244|PDB:1Z6T}. FT HELIX 160 168 {ECO:0000244|PDB:1Z6T}. FT HELIX 171 177 {ECO:0000244|PDB:1Z6T}. FT STRAND 182 189 {ECO:0000244|PDB:1Z6T}. FT HELIX 192 206 {ECO:0000244|PDB:1Z6T}. FT HELIX 220 233 {ECO:0000244|PDB:1Z6T}. FT STRAND 239 245 {ECO:0000244|PDB:1Z6T}. FT HELIX 248 252 {ECO:0000244|PDB:1Z6T}. FT STRAND 259 265 {ECO:0000244|PDB:1Z6T}. FT HELIX 267 270 {ECO:0000244|PDB:1Z6T}. FT STRAND 277 281 {ECO:0000244|PDB:1Z6T}. FT HELIX 288 299 {ECO:0000244|PDB:1Z6T}. FT HELIX 303 305 {ECO:0000244|PDB:1Z6T}. FT HELIX 309 316 {ECO:0000244|PDB:1Z6T}. FT TURN 317 319 {ECO:0000244|PDB:1Z6T}. FT HELIX 321 333 {ECO:0000244|PDB:1Z6T}. FT HELIX 338 346 {ECO:0000244|PDB:1Z6T}. FT HELIX 362 373 {ECO:0000244|PDB:1Z6T}. FT TURN 377 379 {ECO:0000244|PDB:1Z6T}. FT HELIX 380 385 {ECO:0000244|PDB:1Z6T}. FT HELIX 386 388 {ECO:0000244|PDB:1Z6T}. FT HELIX 397 404 {ECO:0000244|PDB:1Z6T}. FT HELIX 408 420 {ECO:0000244|PDB:1Z6T}. FT STRAND 423 429 {ECO:0000244|PDB:1Z6T}. FT STRAND 432 436 {ECO:0000244|PDB:1Z6T}. FT HELIX 439 448 {ECO:0000244|PDB:1Z6T}. FT HELIX 450 452 {ECO:0000244|PDB:1Z6T}. FT HELIX 453 464 {ECO:0000244|PDB:1Z6T}. FT TURN 465 467 {ECO:0000244|PDB:1Z6T}. FT HELIX 470 472 {ECO:0000244|PDB:1Z6T}. FT HELIX 480 493 {ECO:0000244|PDB:1Z6T}. FT HELIX 497 504 {ECO:0000244|PDB:1Z6T}. FT HELIX 507 517 {ECO:0000244|PDB:1Z6T}. FT HELIX 520 528 {ECO:0000244|PDB:1Z6T}. FT HELIX 530 532 {ECO:0000244|PDB:1Z6T}. FT HELIX 535 550 {ECO:0000244|PDB:1Z6T}. FT TURN 551 556 {ECO:0000244|PDB:1Z6T}. FT HELIX 563 567 {ECO:0000244|PDB:1Z6T}. FT HELIX 575 585 {ECO:0000244|PDB:1Z6T}. SQ SEQUENCE 1248 AA; 141840 MW; 0750D05817AC9B3B CRC64; MDAKARNCLL QHREALEKDI KTSYIMDHMI SDGFLTISEE EKVRNEPTQQ QRAAMLIKMI LKKDNDSYVS FYNALLHEGY KDLAALLHDG IPVVSSSSGK DSVSGITSYV RTVLCEGGVP QRPVVFVTRK KLVNAIQQKL SKLKGEPGWV TIHGMAGCGK SVLAAEAVRD HSLLEGCFPG GVHWVSVGKQ DKSGLLMKLQ NLCTRLDQDE SFSQRLPLNI EEAKDRLRIL MLRKHPRSLL ILDDVWDSWV LKAFDSQCQI LLTTRDKSVT DSVMGPKYVV PVESSLGKEK GLEILSLFVN MKKADLPEQA HSIIKECKGS PLVVSLIGAL LRDFPNRWEY YLKQLQNKQF KRIRKSSSYD YEALDEAMSI SVEMLREDIK DYYTDLSILQ KDVKVPTKVL CILWDMETEE VEDILQEFVN KSLLFCDRNG KSFRYYLHDL QVDFLTEKNC SQLQDLHKKI ITQFQRYHQP HTLSPDQEDC MYWYNFLAYH MASAKMHKEL CALMFSLDWI KAKTELVGPA HLIHEFVEYR HILDEKDCAV SENFQEFLSL NGHLLGRQPF PNIVQLGLCE PETSEVYQQA KLQAKQEVDN GMLYLEWINK KNITNLSRLV VRPHTDAVYH ACFSEDGQRI ASCGADKTLQ VFKAETGEKL LEIKAHEDEV LCCAFSTDDR FIATCSVDKK VKIWNSMTGE LVHTYDEHSE QVNCCHFTNS SHHLLLATGS SDCFLKLWDL NQKECRNTMF GHTNSVNHCR FSPDDKLLAS CSADGTLKLW DATSANERKS INVKQFFLNL EDPQEDMEVI VKCCSWSADG ARIMVAAKNK IFLFDIHTSG LLGEIHTGHH STIQYCDFSP QNHLAVVALS QYCVELWNTD SRSKVADCRG HLSWVHGVMF SPDGSSFLTS SDDQTIRLWE TKKVCKNSAV MLKQEVDVVF QENEVMVLAV DHIRRLQLIN GRTGQIDYLT EAQVSCCCLS PHLQYIAFGD ENGAIEILEL VNNRIFQSRF QHKKTVWHIQ FTADEKTLIS SSDDAEIQVW NWQLDKCIFL RGHQETVKDF RLLKNSRLLS WSFDGTVKVW NIITGNKEKD FVCHQGTVLS CDISHDATKF SSTSADKTAK IWSFDLLLPL HELRGHNGCV RCSAFSVDST LLATGDDNGE IRIWNVSNGE LLHLCAPLSE EGAATHGGWV TDLCFSPDGK MLISAGGYIK WWNVVTGESS QTFYTNGTNL KKIHVSPDFK TYVTVDNLGI LYILQTLE // ID ASC_HUMAN Reviewed; 195 AA. AC Q9ULZ3; Q96D12; Q9BSZ5; Q9HBD0; Q9NXJ8; DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 2. DT 18-JUL-2018, entry version 179. DE RecName: Full=Apoptosis-associated speck-like protein containing a CARD; DE Short=hASC; DE AltName: Full=Caspase recruitment domain-containing protein 5; DE AltName: Full=PYD and CARD domain-containing protein; DE AltName: Full=Target of methylation-induced silencing 1; GN Name=PYCARD; Synonyms=ASC, CARD5, TMS1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Leukemia; RX PubMed=10567338; DOI=10.1074/jbc.274.48.33835; RA Masumoto J., Taniguchi S., Ayukawa K., Sarvotham H., Kishino T., RA Niikawa N., Hidaka E., Katsuyama T., Higuchi T., Sagara J.; RT "ASC, a novel 22-kDa protein, aggregates during apoptosis of human RT promyelocytic leukemia HL-60 cells."; RL J. Biol. Chem. 274:33835-33838(1999). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Fibroblast; RX PubMed=11103776; RA Conway K.E., McConnell B.B., Bowring C.E., Donald C.D., Warren S.T., RA Vertino P.M.; RT "TMS1, a novel proapoptotic caspase recruitment domain protein, is a RT target of methylation-induced gene silencing in human breast RT cancers."; RL Cancer Res. 60:6236-6242(2000). RN [3] RP NUCLEOTIDE SEQUENCE (ISOFORM 2), FUNCTION (ISOFORM 2), AND MASS RP SPECTROMETRY (ISOFORM 2). RX PubMed=19759850; DOI=10.1155/2009/287387; RA Matsushita K., Takeoka M., Sagara J., Itano N., Kurose Y., RA Nakamura A., Taniguchi S.; RT "A splice variant of ASC regulates IL-1beta release and aggregates RT differently from intact ASC."; RL Mediators Inflamm. 2009:287387-287387(2009). RN [4] RP NUCLEOTIDE SEQUENCE (ISOFORM 1). RA Martinon F., Hofmann K., Tschopp J.; RT "Pycard a PYD and CARD containing molecule."; RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE (ISOFORM 1). RA Bertin J.; RT "CARD5 protein is a CARD/PYRIN family member that is involved in RT apoptosis signal transduction."; RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon mucosa; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 4-195 (ISOFORM 1). RC TISSUE=Lymph, and Pancreas; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=11103777; RA McConnell B.B., Vertino P.M.; RT "Activation of a caspase-9-mediated apoptotic pathway by subcellular RT redistribution of the novel caspase recruitment domain protein TMS1."; RL Cancer Res. 60:6243-6247(2000). RN [9] RP INTERACTION WITH NLRC4. RX PubMed=11374873; DOI=10.1006/bbrc.2001.4928; RA Geddes B.J., Wang L., Huang W.-J., Lavellee M., Manji G.A., Brown M., RA Jurman M., Cao J., Morgenstern J., Merriam S., Glucksmann M.A., RA DiStefano P.S., Bertin J.; RT "Human CARD12 is a novel CED4/Apaf-1 family member that induces RT apoptosis."; RL Biochem. Biophys. Res. Commun. 284:77-82(2001). RN [10] RP INTERACTION WITH MEFV. RX PubMed=11498534; DOI=10.1074/jbc.M104730200; RA Richards N., Schaner P., Diaz A., Stuckey J., Shelden E., Wadhwa A., RA Gumucio D.L.; RT "Interaction between pyrin and the apoptotic speck protein (ASC) RT modulates ASC-induced apoptosis."; RL J. Biol. Chem. 276:39320-39329(2001). RN [11] RP INTERACTION WITH NLRP3, AND DOMAIN. RX PubMed=11786556; DOI=10.1074/jbc.M112208200; RA Manji G.A., Wang L., Geddes B.J., Brown M., Merriam S., Al-Garawi A., RA Mak S., Lora J.M., Briskin M., Jurman M., Cao J., DiStefano P.S., RA Bertin J.; RT "PYPAF1: a PYRIN-containing APAF1-like protein that assembles with ASC RT and activates NF-kB."; RL J. Biol. Chem. 277:11570-11575(2002). RN [12] RP INTERACTION WITH CASP1; NLRC4 AND CARD16. RX PubMed=11967258; DOI=10.1074/jbc.C200179200; RA Srinivasula S.M., Poyet J.L., Razmara M., Datta P., Zhang Z., RA Alnemri E.S.; RT "The PYRIN-CARD protein ASC is an activating adaptor for caspase-1."; RL J. Biol. Chem. 277:21119-21122(2002). RN [13] RP FUNCTION, AND INTERACTION WITH CHUK AND IKBKB. RX PubMed=12486103; DOI=10.1084/jem.20021552; RA Stehlik C., Fiorentino L., Dorfleutner A., Bruey J.M., Ariza E.M., RA Sagara J., Reed J.C.; RT "The PAAD/PYRIN-family protein ASC is a dual regulator of a conserved RT step in nuclear factor kappaB activation pathways."; RL J. Exp. Med. 196:1605-1615(2002). RN [14] RP IDENTIFICATION IN NLPR1 INFLAMMASOME. RX PubMed=12191486; DOI=10.1016/S1097-2765(02)00599-3; RA Martinon F., Burns K., Tschopp J.; RT "The inflammasome: a molecular platform triggering activation of RT inflammatory caspases and processing of proIL-beta."; RL Mol. Cell 10:417-426(2002). RN [15] RP FUNCTION IN APOPTOSIS, INTERACTION WITH CASP8, AND MUTAGENESIS OF RP LEU-12. RX PubMed=12646168; DOI=10.1016/S0006-291X(03)00309-7; RA Masumoto J., Dowds T.A., Schaner P., Chen F.F., Ogura Y., Li M., RA Zhu L., Katsuyama T., Sagara J., Taniguchi S., Gumucio D.L., Nunez G., RA Inohara N.; RT "ASC is an activating adaptor for NF-kappa B and caspase-8-dependent RT apoptosis."; RL Biochem. Biophys. Res. Commun. 303:69-73(2003). RN [16] RP INTERACTION WITH PYDC1, DOMAIN, AND PHOSPHORYLATION. RX PubMed=12656673; DOI=10.1042/BJ20030304; RA Stehlik C., Krajewska M., Welsh K., Krajewski S., Godzik A., RA Reed J.C.; RT "The PAAD/PYRIN-only protein POP1/ASC2 is a modulator of ASC-mediated RT nuclear-factor-kappa B and pro-caspase-1 regulation."; RL Biochem. J. 373:101-113(2003). RN [17] RP INTERACTION WITH CASP1 AND RIPK2. RX PubMed=14634131; DOI=10.4049/jimmunol.171.11.6154; RA Stehlik C., Lee S.H., Dorfleutner A., Stassinopoulos A., Sagara J., RA Reed J.C.; RT "Apoptosis-associated speck-like protein containing a caspase RT recruitment domain is a regulator of procaspase-1 activation."; RL J. Immunol. 171:6154-6163(2003). RN [18] RP FUNCTION IN NLRP2 AND NLRP3 INFLAMMASOMES, INTERACTION WITH NLRP2 AND RP NLRP3, AND SUBCELLULAR LOCATION. RX PubMed=15030775; DOI=10.1016/S1074-7613(04)00046-9; RA Agostini L., Martinon F., Burns K., McDermott M.F., Hawkins P.N., RA Tschopp J.; RT "NALP3 forms an IL-1beta-processing inflammasome with increased RT activity in Muckle-Wells autoinflammatory disorder."; RL Immunity 20:319-325(2004). RN [19] RP INTERACTION WITH NLRP10. RX PubMed=15096476; DOI=10.1093/intimm/dxh081; RA Wang Y., Hasegawa M., Imamura R., Kinoshita T., Kondo C., Konaka K., RA Suda T.; RT "PYNOD, a novel Apaf-1/CED4-like protein is an inhibitor of ASC and RT caspase-1."; RL Int. Immunol. 16:777-786(2004). RN [20] RP INTERACTION WITH NLRP3. RX PubMed=15020601; DOI=10.1074/jbc.M401178200; RA Dowds T.A., Masumoto J., Zhu L., Inohara N., Nunez G.; RT "Cryopyrin-induced interleukin 1beta secretion in monocytic cells: RT enhanced activity of disease-associated mutants and requirement for RT ASC."; RL J. Biol. Chem. 279:21924-21928(2004). RN [21] RP INTERACTION WITH NLRP2, AND MUTAGENESIS OF GLU-13. RX PubMed=15456791; DOI=10.1074/jbc.M406741200; RA Bruey J.-M., Bruey-Sedano N., Newman R., Chandler S., Stehlik C., RA Reed J.C.; RT "PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates RT NF-kappaB and caspase-1 activation in macrophages."; RL J. Biol. Chem. 279:51897-51907(2004). RN [22] RP FUNCTION IN APOPTOSIS, SUBCELLULAR LOCATION, AND INTERACTION WITH BAX. RX PubMed=14730312; DOI=10.1038/ncb1087; RA Ohtsuka T., Ryu H., Minamishima Y.A., Macip S., Sagara J., RA Nakayama K.I., Aaronson S.A., Lee S.W.; RT "ASC is a Bax adaptor and regulates the p53-Bax mitochondrial RT apoptosis pathway."; RL Nat. Cell Biol. 6:121-128(2004). RN [23] RP SELF-ASSOCIATION, AND MUTAGENESIS OF ILE-8; LEU-12; GLU-13; LEU-15; RP GLU-19; LEU-20; LYS-21; PHE-23; LEU-25; LYS-26; LEU-27; PRO-40; RP ARG-41; LEU-45; MET-47; ASP-48; LEU-52; LEU-56; GLU-62; GLU-67; RP LEU-68; VAL-72 AND MET-76. RX PubMed=15641782; DOI=10.1021/bi048374i; RA Moriya M., Taniguchi S., Wu P., Liepinsh E., Otting G., Sagara J.; RT "Role of charged and hydrophobic residues in the oligomerization of RT the PYRIN domain of ASC."; RL Biochemistry 44:575-583(2005). RN [24] RP ASSOCIATION WITH INFLAMMASOMES. RX PubMed=16037825; DOI=10.1038/sj.cdd.4401734; RA Yu J.W., Wu J., Zhang Z., Datta P., Ibrahimi I., Taniguchi S., RA Sagara J., Fernandes-Alnemri T., Alnemri E.S.; RT "Cryopyrin and pyrin activate caspase-1, but not NF-kappaB, via ASC RT oligomerization."; RL Cell Death Differ. 13:236-249(2006). RN [25] RP FUNCTION, AND INTERACTION WITH CASP1. RX PubMed=16585594; DOI=10.4049/jimmunol.176.8.4979; RA Sarkar A., Duncan M., Hart J., Hertlein E., Guttridge D.C., RA Wewers M.D.; RT "ASC directs NF-kappaB activation by regulating receptor interacting RT protein-2 (RIP2) caspase-1 interactions."; RL J. Immunol. 176:4979-4986(2006). RN [26] RP FUNCTION. RX PubMed=16982856; DOI=10.4049/jimmunol.177.7.4252; RA Taxman D.J., Zhang J., Champagne C., Bergstralh D.T., Iocca H.A., RA Lich J.D., Ting J.P.; RT "ASC mediates the induction of multiple cytokines by Porphyromonas RT gingivalis via caspase-1-dependent and -independent pathways."; RL J. Immunol. 177:4252-4256(2006). RN [27] RP FUNCTION, AND SUBUNIT. RX PubMed=17599095; DOI=10.1038/sj.cdd.4402194; RA Fernandes-Alnemri T., Wu J., Yu J.W., Datta P., Miller B., RA Jankowski W., Rosenberg S., Zhang J., Alnemri E.S.; RT "The pyroptosome: a supramolecular assembly of ASC dimers mediating RT inflammatory cell death via caspase-1 activation."; RL Cell Death Differ. 14:1590-1604(2007). RN [28] RP FUNCTION IN NLRP1 INFLAMMASOME. RX PubMed=17349957; DOI=10.1016/j.molcel.2007.01.032; RA Faustin B., Lartigue L., Bruey J.-M., Luciano F., Sergienko E., RA Bailly-Maitre B., Volkmann N., Hanein D., Rouiller I., Reed J.C.; RT "Reconstituted NALP1 inflammasome reveals two-step mechanism of RT caspase-1 activation."; RL Mol. Cell 25:713-724(2007). RN [29] RP FUNCTION IN APOPTOSIS. RX PubMed=16964285; DOI=10.1038/sj.onc.1209965; RA Hasegawa M., Kawase K., Inohara N., Imamura R., Yeh W.C., RA Kinoshita T., Suda T.; RT "Mechanism of ASC-mediated apoptosis: bid-dependent apoptosis in type RT II cells."; RL Oncogene 26:1748-1756(2007). RN [30] RP INTERACTION WITH PYDC1 AND PYDC2, AND DOMAIN. RX PubMed=17178784; DOI=10.1128/IAI.01315-06; RA Dorfleutner A., Bryan N.B., Talbott S.J., Funya K.N., Rellick S.L., RA Reed J.C., Shi X., Rojanasakul Y., Flynn D.C., Stehlik C.; RT "Cellular pyrin domain-only protein 2 is a candidate regulator of RT inflammasome activation."; RL Infect. Immun. 75:1484-1492(2007). RN [31] RP INTERACTION WITH PYDC2. RX PubMed=17339483; DOI=10.4049/jimmunol.178.6.3837; RA Bedoya F., Sandler L.L., Harton J.A.; RT "Pyrin-only protein 2 modulates NF-kappaB and disrupts ASC:CLR RT interactions."; RL J. Immunol. 178:3837-3845(2007). RN [32] RP INTERACTION WITH PYDC1, AND MUTAGENESIS OF GLU-13; TYR-36 AND ASP-48. RX PubMed=18362139; DOI=10.1074/jbc.M801589200; RA Srimathi T., Robbins S.L., Dubas R.L., Chang H., Cheng H., Roder H., RA Park Y.C.; RT "Mapping of POP1-binding site on pyrin domain of ASC."; RL J. Biol. Chem. 283:15390-15398(2008). RN [33] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=19234215; DOI=10.4049/jimmunol.0802367; RA Bryan N.B., Dorfleutner A., Rojanasakul Y., Stehlik C.; RT "Activation of inflammasomes requires intracellular redistribution of RT the apoptotic speck-like protein containing a caspase recruitment RT domain."; RL J. Immunol. 182:3173-3182(2009). RN [34] RP FUNCTION. RX PubMed=19494289; DOI=10.4049/jimmunol.0800448; RA Hasegawa M., Imamura R., Motani K., Nishiuchi T., Matsumoto N., RA Kinoshita T., Suda T.; RT "Mechanism and repertoire of ASC-mediated gene expression."; RL J. Immunol. 182:7655-7662(2009). RN [35] RP FUNCTION IN AIM2 INFLAMMASOME, INTERACTION WITH AIM2, AND DOMAIN. RX PubMed=19158676; DOI=10.1038/nature07710; RA Fernandes-Alnemri T., Yu J.W., Datta P., Wu J., Alnemri E.S.; RT "AIM2 activates the inflammasome and cell death in response to RT cytoplasmic DNA."; RL Nature 458:509-513(2009). RN [36] RP FUNCTION IN AIM2 INFLAMMASOME, INTERACTION WITH AIM2, AND DOMAIN. RX PubMed=19158675; DOI=10.1038/nature07725; RA Hornung V., Ablasser A., Charrel-Dennis M., Bauernfeind F., RA Horvath G., Caffrey D.R., Latz E., Fitzgerald K.A.; RT "AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating RT inflammasome with ASC."; RL Nature 458:514-518(2009). RN [37] RP FUNCTION (ISOFORMS 2 AND 3). RX PubMed=20482797; DOI=10.1186/1476-9255-7-23; RA Bryan N.B., Dorfleutner A., Kramer S.J., Yun C., Rojanasakul Y., RA Stehlik C.; RT "Differential splicing of the apoptosis-associated speck like protein RT containing a caspase recruitment domain (ASC) regulates RT inflammasomes."; RL J. Inflamm. (Lond.) 7:23-23(2010). RN [38] RP INTERACTION WITH DDX58. RX PubMed=19915568; DOI=10.1038/ni.1824; RA Poeck H., Bscheider M., Gross O., Finger K., Roth S., Rebsamen M., RA Hannesschlager N., Schlee M., Rothenfusser S., Barchet W., Kato H., RA Akira S., Inoue S., Endres S., Peschel C., Hartmann G., Hornung V., RA Ruland J.; RT "Recognition of RNA virus by RIG-I results in activation of CARD9 and RT inflammasome signaling for interleukin 1 beta production."; RL Nat. Immunol. 11:63-69(2010). RN [39] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [40] RP INTERACTION WITH IFI16. RX PubMed=21575908; DOI=10.1016/j.chom.2011.04.008; RA Kerur N., Veettil M.V., Sharma-Walia N., Bottero V., Sadagopan S., RA Otageri P., Chandran B.; RT "IFI16 acts as a nuclear pathogen sensor to induce the inflammasome in RT response to Kaposi Sarcoma-associated herpesvirus infection."; RL Cell Host Microbe 9:363-375(2011). RN [41] RP FUNCTION. RX PubMed=21487011; DOI=10.1074/jbc.M111.221077; RA Taxman D.J., Holley-Guthrie E.A., Huang M.T., Moore C.B., RA Bergstralh D.T., Allen I.C., Lei Y., Gris D., Ting J.P.; RT "The NLR adaptor ASC/PYCARD regulates DUSP10, mitogen-activated RT protein kinase (MAPK), and chemokine induction independent of the RT inflammasome."; RL J. Biol. Chem. 286:19605-19616(2011). RN [42] RP FUNCTION. RX PubMed=22732093; DOI=10.1016/j.humimm.2012.06.008; RA Guo X., Dhodapkar K.M.; RT "Central and overlapping role of cathepsin B and inflammasome adaptor RT ASC in antigen presenting function of human dendritic cells."; RL Hum. Immunol. 73:871-878(2012). RN [43] RP SUBCELLULAR LOCATION. RX PubMed=21124315; DOI=10.1038/nature09663; RA Zhou R., Yazdi A.S., Menu P., Tschopp J.; RT "A role for mitochondria in NLRP3 inflammasome activation."; RL Nature 469:221-225(2011). RN [44] RP INDUCTION BY ENDOCANNABINOID ANANDAMIDE. RX PubMed=23955712; DOI=10.1038/nm.3265; RA Jourdan T., Godlewski G., Cinar R., Bertola A., Szanda G., Liu J., RA Tam J., Han T., Mukhopadhyay B., Skarulis M.C., Ju C., Aouadi M., RA Czech M.P., Kunos G.; RT "Activation of the Nlrp3 inflammasome in infiltrating macrophages by RT endocannabinoids mediates beta cell loss in type 2 diabetes."; RL Nat. Med. 19:1132-1140(2013). RN [45] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [46] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [47] RP FUNCTION. RX PubMed=28314590; DOI=10.1016/j.immuni.2017.02.011; RA Wang Y., Ning X., Gao P., Wu S., Sha M., Lv M., Zhou X., Gao J., RA Fang R., Meng G., Su X., Jiang Z.; RT "Inflammasome activation triggers caspase-1-mediated cleavage of cGAS RT to regulate responses to DNA virus infection."; RL Immunity 46:393-404(2017). RN [48] RP STRUCTURE BY NMR OF 1-91, AND DOMAIN. RX PubMed=14499617; DOI=10.1016/j.jmb.2003.07.007; RA Liepinsh E., Barbals R., Dahl E., Sharipo A., Staub E., Otting G.; RT "The death-domain fold of the ASC PYRIN domain, presenting a basis for RT PYRIN/PYRIN recognition."; RL J. Mol. Biol. 332:1155-1163(2003). RN [49] RP STRUCTURE BY NMR. RX PubMed=19759015; DOI=10.1074/jbc.M109.024273; RA de Alba E.; RT "Structure and interdomain dynamics of apoptosis-associated speck-like RT protein containing a CARD (ASC)."; RL J. Biol. Chem. 284:32932-32941(2009). CC -!- FUNCTION: Functions as key mediator in apoptosis and inflammation. CC Promotes caspase-mediated apoptosis involving predominantly CC caspase-8 and also caspase-9 in a probable cell type-specific CC manner. Involved in activation of the mitochondrial apoptotic CC pathway, promotes caspase-8-dependent proteolytic maturation of CC BID independently of FADD in certain cell types and also mediates CC mitochondrial translocation of BAX and activates BAX-dependent CC apoptosis coupled to activation of caspase-9, -2 and -3. Involved CC in macrophage pyroptosis, a caspase-1-dependent inflammatory form CC of cell death and is the major constituent of the ASC pyroptosome CC which forms upon potassium depletion and rapidly recruits and CC activates caspase-1. In innate immune response believed to act as CC an integral adapter in the assembly of the inflammasome which CC activates caspase-1 leading to processing and secretion of CC proinflammatory cytokines. The function as activating adapter in CC different types of inflammasomes is mediated by the pyrin and CARD CC domains and their homotypic interactions. Required for recruitment CC of caspase-1 to inflammasomes containing certain pattern CC recognition receptors, such as NLRP2, NLRP3, AIM2 and probably CC IFI16. In the NLRP1 and NLRC4 inflammasomes seems not be required CC but facilitates the processing of procaspase-1. In cooperation CC with NOD2 involved in an inflammasome activated by bacterial CC muramyl dipeptide leading to caspase-1 activation. May be involved CC in DDX58-triggered proinflammatory responses and inflammasome CC activation. Isoform 2 may have a regulating effect on the function CC as inflammasome adapter. Isoform 3 seems to inhibit inflammasome- CC mediated maturation of interleukin-1 beta. In collaboration with CC AIM2 which detects cytosolic double-stranded DNA may also be CC involved in a caspase-1-independent cell death that involves CC caspase-8. In adaptive immunity may be involved in maturation of CC dendritic cells to stimulate T-cell immunity and in cytoskeletal CC rearrangements coupled to chemotaxis and antigen uptake may be CC involved in post-transcriptional regulation of the guanine CC nucleotide exchange factor DOCK2; the latter function is proposed CC to involve the nuclear form. Also involved in transcriptional CC activation of cytokines and chemokines independent of the CC inflammasome; this function may involve AP-1, NF-kappa-B, MAPK and CC caspase-8 signaling pathways. For regulation of NF-kappa-B CC activating and inhibiting functions have been reported. Modulates CC NF-kappa-B induction at the level of the IKK complex by inhibiting CC kinase activity of CHUK and IKBK. Proposed to compete with RIPK2 CC for association with CASP1 thereby down-regulating CASP1-mediated CC RIPK2-dependent NF-kappa-B activation and activating interleukin-1 CC beta processing. Modulates host resistance to DNA virus infection, CC probably by inducing the cleavage of and inactivating CGAS in CC presence of cytoplasmic double-stranded DNA (PubMed:28314590). CC {ECO:0000269|PubMed:11103777, ECO:0000269|PubMed:12486103, CC ECO:0000269|PubMed:12646168, ECO:0000269|PubMed:14499617, CC ECO:0000269|PubMed:14730312, ECO:0000269|PubMed:15030775, CC ECO:0000269|PubMed:16585594, ECO:0000269|PubMed:16964285, CC ECO:0000269|PubMed:16982856, ECO:0000269|PubMed:17349957, CC ECO:0000269|PubMed:17599095, ECO:0000269|PubMed:19158675, CC ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19234215, CC ECO:0000269|PubMed:19494289, ECO:0000269|PubMed:21487011, CC ECO:0000269|PubMed:22732093, ECO:0000269|PubMed:28314590}. CC -!- SUBUNIT: Self-associates; enforced oligomerization induces CC apoptosis, NF-kappa-B regulation and interleukin-1 beta secretion. CC Homooligomers can form disk-like particles of approximately 12 nm CC diameter and approximately 1 nm height. Next to isorm 1 also CC isoform 2 and isoform 3 may be involved in oligomerization leading CC to functional regulation. Component of several inflammasomes CC containing one pattern recognition receptor/sensor, such as NLRP1, CC NLRP2, NLRP3, AIM2, MEFV or NOD2, and probably NLRC4, NLRP12 or CC IFI16. Major component of the ASC pyroptosome, a 1-2 um CC supramolecular assembly (one per macrophage cell) which consists CC of oligomerized PYCARD dimers and CASP1. Interacts with CASP1 CC (precursor form); the interaction induces activation of CASP1 CC leading to the processing of interleukin-1 beta; PYCARD competes CC with RIPK2 for binding to CASP1. Interacts with NLRP3; the CC interaction requires the homooligomerization of NLRP3. Interacts CC with NLRP2, NLRC4, MEFV, CARD16, AIM2, IFI16, NOD2, DDX58, RIPK2, CC PYDC1, PYDC2, NLRP10, CASP8, CHUK, IKBKB and BAX. CC {ECO:0000269|PubMed:11374873, ECO:0000269|PubMed:11498534, CC ECO:0000269|PubMed:11786556, ECO:0000269|PubMed:11967258, CC ECO:0000269|PubMed:12191486, ECO:0000269|PubMed:12486103, CC ECO:0000269|PubMed:12646168, ECO:0000269|PubMed:12656673, CC ECO:0000269|PubMed:14634131, ECO:0000269|PubMed:14730312, CC ECO:0000269|PubMed:15020601, ECO:0000269|PubMed:15030775, CC ECO:0000269|PubMed:15096476, ECO:0000269|PubMed:15456791, CC ECO:0000269|PubMed:16585594, ECO:0000269|PubMed:17178784, CC ECO:0000269|PubMed:17339483, ECO:0000269|PubMed:17599095, CC ECO:0000269|PubMed:18362139, ECO:0000269|PubMed:19158675, CC ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19915568, CC ECO:0000269|PubMed:21575908}. CC -!- INTERACTION: CC Self; NbExp=8; IntAct=EBI-751215, EBI-751215; CC O14862:AIM2; NbExp=13; IntAct=EBI-751215, EBI-6253193; CC Q07812:BAX; NbExp=7; IntAct=EBI-751215, EBI-516580; CC P29466:CASP1; NbExp=9; IntAct=EBI-751215, EBI-516667; CC O00471:EXOC5; NbExp=5; IntAct=EBI-751215, EBI-949824; CC O15553:MEFV; NbExp=10; IntAct=EBI-751215, EBI-7644532; CC Q7RTR2:NLRC3; NbExp=3; IntAct=EBI-751215, EBI-1042625; CC Q9C000:NLRP1; NbExp=5; IntAct=EBI-751215, EBI-1220518; CC Q96P20:NLRP3; NbExp=9; IntAct=EBI-751215, EBI-6253230; CC Q56P42:PYDC2; NbExp=4; IntAct=EBI-751215, EBI-6374418; CC Q13546:RIPK1; NbExp=2; IntAct=EBI-751215, EBI-358507; CC P43405:SYK; NbExp=4; IntAct=EBI-751215, EBI-78302; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Endoplasmic reticulum. CC Mitochondrion. Nucleus. Note=Upstream of caspase activation, a CC redistribution from the cytoplasm to the aggregates occurs. These CC appear as hollow, perinuclear spherical, ball-like structures. CC Upon NLRP3 inflammasome activation redistributes to the CC perinuclear space localizing to endoplasmic reticulum and CC mitochondria. Localized primarily to the nucleus in resting CC monocytes/macrophages and rapidly redistributed to the cytoplasm CC upon pathogen infection. Localized to large cytoplasmic aggregate CC appearing as a speck containing AIM2, PYCARD, CASP8 and bacterial CC DNA after infection with Francisella tularensis (By similarity). CC {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=fASC; CC IsoId=Q9ULZ3-1; Sequence=Displayed; CC Name=2; Synonyms=Asc-b, vASC; CC IsoId=Q9ULZ3-2; Sequence=VSP_004119; CC Name=3; Synonyms=Asc-c; CC IsoId=Q9ULZ3-3; Sequence=VSP_004118; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Widely expressed at low levels. Detected in CC peripheral blood leukocytes, lung, small intestine, spleen, CC thymus, colon and at lower levels in placenta, liver and kidney. CC Very low expression in skeletal muscle, heart and brain. Detected CC in the leukemia cell lines HL-60 and U-937, but not in Jurkat T- CC cell lymphoma and Daudi Burkitt's lymphoma. Detected in the CC melanoma cell line WM35, but not in WM793. Not detected in HeLa CC cervical carcinoma cells and MOLT-4 lymphocytic leukemia cells. CC -!- INDUCTION: In macrophages, up-regulated by endocannabinoid CC anandamide/AEA. {ECO:0000269|PubMed:23955712}. CC -!- DOMAIN: The CARD domain mediates interaction with CASP1 and NLRC4 CC (PubMed:14634131 and PubMed:11967258). CC {ECO:0000269|PubMed:11786556}. CC -!- DOMAIN: The pyrin domain mediates homotypic interactions with CC pyrin domains of proteins such as of NLRP3, PYDC1, PYDC2 and AIM2. CC {ECO:0000269|PubMed:11786556, ECO:0000269|PubMed:12656673, CC ECO:0000269|PubMed:14499617, ECO:0000269|PubMed:17178784, CC ECO:0000269|PubMed:19158675, ECO:0000269|PubMed:19158676}. CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:12656673}. CC -!- MISCELLANEOUS: In breast tumorigenesis, methylation-mediated CC silencing may affect genes and proteins that act as positive CC mediators of cell death. CC -!- SEQUENCE CAUTION: CC Sequence=BAA91012.1; Type=Frameshift; Positions=4; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AB023416; BAA87339.2; -; mRNA. DR EMBL; AF184072; AAG01187.1; -; Genomic_DNA. DR EMBL; AF184073; AAG01188.1; -; mRNA. DR EMBL; AF255794; AAF99665.1; -; mRNA. DR EMBL; AF310103; AAG30286.1; -; mRNA. DR EMBL; AF384665; AAK63850.1; -; mRNA. DR EMBL; AK000211; BAA91012.1; ALT_FRAME; mRNA. DR EMBL; BC004470; AAH04470.1; -; mRNA. DR EMBL; BC013569; AAH13569.2; -; mRNA. DR CCDS; CCDS10708.1; -. [Q9ULZ3-1] DR CCDS; CCDS10709.1; -. [Q9ULZ3-2] DR RefSeq; NP_037390.2; NM_013258.4. [Q9ULZ3-1] DR RefSeq; NP_660183.1; NM_145182.2. [Q9ULZ3-2] DR UniGene; Hs.499094; -. DR PDB; 1UCP; NMR; -; A=1-91. DR PDB; 2KN6; NMR; -; A=1-195. DR PDB; 3J63; EM; 3.80 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O=1-91. DR PDB; 5H8O; X-ray; 4.21 A; B=115-195. DR PDBsum; 1UCP; -. DR PDBsum; 2KN6; -. DR PDBsum; 3J63; -. DR PDBsum; 5H8O; -. DR ProteinModelPortal; Q9ULZ3; -. DR SMR; Q9ULZ3; -. DR BioGrid; 118876; 45. DR CORUM; Q9ULZ3; -. DR DIP; DIP-27618N; -. DR IntAct; Q9ULZ3; 48. DR MINT; Q9ULZ3; -. DR STRING; 9606.ENSP00000247470; -. DR iPTMnet; Q9ULZ3; -. DR PhosphoSitePlus; Q9ULZ3; -. DR BioMuta; PYCARD; -. DR DMDM; 18203507; -. DR EPD; Q9ULZ3; -. DR PaxDb; Q9ULZ3; -. DR PeptideAtlas; Q9ULZ3; -. DR PRIDE; Q9ULZ3; -. DR ProteomicsDB; 85158; -. DR ProteomicsDB; 85159; -. [Q9ULZ3-2] DR ProteomicsDB; 85160; -. [Q9ULZ3-3] DR DNASU; 29108; -. DR Ensembl; ENST00000247470; ENSP00000247470; ENSG00000103490. [Q9ULZ3-1] DR Ensembl; ENST00000350605; ENSP00000340441; ENSG00000103490. [Q9ULZ3-2] DR GeneID; 29108; -. DR KEGG; hsa:29108; -. DR UCSC; uc002ebm.4; human. [Q9ULZ3-1] DR CTD; 29108; -. DR DisGeNET; 29108; -. DR EuPathDB; HostDB:ENSG00000103490.13; -. DR GeneCards; PYCARD; -. DR H-InvDB; HIX0012985; -. DR HGNC; HGNC:16608; PYCARD. DR HPA; CAB006853; -. DR HPA; CAB015948; -. DR HPA; HPA049074; -. DR HPA; HPA054496; -. DR MIM; 606838; gene. DR neXtProt; NX_Q9ULZ3; -. DR OpenTargets; ENSG00000103490; -. DR PharmGKB; PA134950175; -. DR eggNOG; ENOG410J02A; Eukaryota. DR eggNOG; ENOG4111XEQ; LUCA. DR GeneTree; ENSGT00440000033973; -. DR HOGENOM; HOG000034090; -. DR HOVERGEN; HBG018739; -. DR InParanoid; Q9ULZ3; -. DR KO; K12799; -. DR OMA; AWNLTCK; -. DR OrthoDB; EOG091G0OWO; -. DR PhylomeDB; Q9ULZ3; -. DR TreeFam; TF337882; -. DR Reactome; R-HSA-5660668; CLEC7A/inflammasome pathway. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-844456; The NLRP3 inflammasome. DR Reactome; R-HSA-844615; The AIM2 inflammasome. DR SIGNOR; Q9ULZ3; -. DR ChiTaRS; PYCARD; human. DR EvolutionaryTrace; Q9ULZ3; -. DR GeneWiki; PYCARD; -. DR GenomeRNAi; 29108; -. DR PRO; PR:Q9ULZ3; -. DR Proteomes; UP000005640; Chromosome 16. DR Bgee; ENSG00000103490; -. DR CleanEx; HS_PYCARD; -. DR ExpressionAtlas; Q9ULZ3; baseline and differential. DR Genevisible; Q9ULZ3; HS. DR GO; GO:0097169; C:AIM2 inflammasome complex; IDA:UniProtKB. DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0008385; C:IkappaB kinase complex; TAS:HGNC. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0072558; C:NLRP1 inflammasome complex; IDA:UniProtKB. DR GO; GO:0072559; C:NLRP3 inflammasome complex; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:HPA. DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome. DR GO; GO:0070700; F:BMP receptor binding; IPI:AgBase. DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; NAS:UniProtKB. DR GO; GO:0097153; F:cysteine-type endopeptidase activity involved in apoptotic process; IBA:GO_Central. DR GO; GO:0019899; F:enzyme binding; IPI:AgBase. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0005138; F:interleukin-6 receptor binding; IPI:AgBase. DR GO; GO:0017024; F:myosin I binding; IPI:AgBase. DR GO; GO:0002020; F:protease binding; IPI:AgBase. DR GO; GO:0042803; F:protein homodimerization activity; IDA:HGNC. DR GO; GO:0032090; F:Pyrin domain binding; IPI:HGNC. DR GO; GO:0005523; F:tropomyosin binding; IPI:AgBase. DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; NAS:UniProtKB. DR GO; GO:0002218; P:activation of innate immune response; IDA:UniProtKB. DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc. DR GO; GO:0071347; P:cellular response to interleukin-1; IDA:UniProtKB. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:UniProtKB. DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:UniProtKB. DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB. DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; IMP:UniProtKB. DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IMP:UniProtKB. DR GO; GO:0044351; P:macropinocytosis; ISS:UniProtKB. DR GO; GO:0001773; P:myeloid dendritic cell activation; IMP:UniProtKB. DR GO; GO:0002277; P:myeloid dendritic cell activation involved in immune response; ISS:UniProtKB. DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB. DR GO; GO:0032688; P:negative regulation of interferon-beta production; IMP:UniProtKB. DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IMP:UniProtKB. DR GO; GO:0071901; P:negative regulation of protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0043312; P:neutrophil degranulation; TAS:Reactome. DR GO; GO:0030838; P:positive regulation of actin filament polymerization; ISS:UniProtKB. DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; ISS:UniProtKB. DR GO; GO:0002821; P:positive regulation of adaptive immune response; IMP:UniProtKB. DR GO; GO:0002588; P:positive regulation of antigen processing and presentation of peptide antigen via MHC class II; ISS:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0090197; P:positive regulation of chemokine secretion; IMP:UniProtKB. DR GO; GO:2001056; P:positive regulation of cysteine-type endopeptidase activity; IDA:UniProtKB. DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:HGNC. DR GO; GO:0051091; P:positive regulation of DNA binding transcription factor activity; IDA:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB. DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IDA:UniProtKB. DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISS:UniProtKB. DR GO; GO:0050718; P:positive regulation of interleukin-1 beta secretion; IDA:HGNC. DR GO; GO:2001181; P:positive regulation of interleukin-10 secretion; IMP:UniProtKB. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB. DR GO; GO:2000778; P:positive regulation of interleukin-6 secretion; IMP:UniProtKB. DR GO; GO:2000484; P:positive regulation of interleukin-8 secretion; IMP:UniProtKB. DR GO; GO:0046330; P:positive regulation of JNK cascade; IMP:UniProtKB. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB. DR GO; GO:0050766; P:positive regulation of phagocytosis; ISS:UniProtKB. DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; IDA:UniProtKB. DR GO; GO:0050870; P:positive regulation of T cell activation; IMP:UniProtKB. DR GO; GO:2000406; P:positive regulation of T cell migration; ISS:UniProtKB. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:UniProtKB. DR GO; GO:2001242; P:regulation of intrinsic apoptotic signaling pathway; IDA:UniProtKB. DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB. DR GO; GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB. DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IDA:HGNC. DR CDD; cd08330; CARD_ASC_NALP1; 1. DR InterPro; IPR001315; CARD. DR InterPro; IPR033516; CARD8/ASC/NALP1_CARD. DR InterPro; IPR004020; DAPIN. DR InterPro; IPR011029; DEATH-like_dom_sf. DR Pfam; PF00619; CARD; 1. DR Pfam; PF02758; PYRIN; 1. DR SMART; SM01289; PYRIN; 1. DR SUPFAM; SSF47986; SSF47986; 2. DR PROSITE; PS50209; CARD; 1. DR PROSITE; PS50824; DAPIN; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; Complete proteome; KW Cytoplasm; Endoplasmic reticulum; Immunity; Inflammatory response; KW Innate immunity; Mitochondrion; Nucleus; Phosphoprotein; KW Reference proteome; Tumor suppressor. FT CHAIN 1 195 Apoptosis-associated speck-like protein FT containing a CARD. FT /FTId=PRO_0000064692. FT DOMAIN 1 91 Pyrin. {ECO:0000255|PROSITE- FT ProRule:PRU00061}. FT DOMAIN 107 195 CARD. {ECO:0000255|PROSITE- FT ProRule:PRU00046}. FT MOD_RES 195 195 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9EPB4}. FT VAR_SEQ 26 85 Missing (in isoform 3). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_004118. FT VAR_SEQ 93 111 Missing (in isoform 2). FT {ECO:0000303|PubMed:11103776}. FT /FTId=VSP_004119. FT MUTAGEN 8 8 I->A: Abolishes homooligomerization. FT {ECO:0000269|PubMed:15641782}. FT MUTAGEN 12 12 L->A: Abolishes homooligomerization. FT {ECO:0000269|PubMed:12646168, FT ECO:0000269|PubMed:15641782}. FT MUTAGEN 12 12 L->Q: Abolishes promotion of apoptosis FT and NF-kappa-B activation. FT {ECO:0000269|PubMed:12646168, FT ECO:0000269|PubMed:15641782}. FT MUTAGEN 13 13 E->A: Abolishes interaction with PYDC1. FT {ECO:0000269|PubMed:15456791, FT ECO:0000269|PubMed:15641782, FT ECO:0000269|PubMed:18362139}. FT MUTAGEN 13 13 E->W: Abolishes interaction with NLRP2. FT {ECO:0000269|PubMed:15456791, FT ECO:0000269|PubMed:15641782, FT ECO:0000269|PubMed:18362139}. FT MUTAGEN 15 15 L->A: Abolishes homooligomerization. FT {ECO:0000269|PubMed:15641782}. FT MUTAGEN 19 19 E->A: Abolishes homooligomerization. FT {ECO:0000269|PubMed:15641782}. FT MUTAGEN 20 20 L->A: Abolishes homooligomerization. FT {ECO:0000269|PubMed:15641782}. FT MUTAGEN 21 21 K->A,E,Q: Abolishes homooligomerization. FT {ECO:0000269|PubMed:15641782}. FT MUTAGEN 23 23 F->A: Abolishes homooligomerization. FT {ECO:0000269|PubMed:15641782}. FT MUTAGEN 25 25 L->A,E,G,K,N,Q: Abolishes FT homooligomerization. FT {ECO:0000269|PubMed:15641782}. FT MUTAGEN 26 26 K->A,Q: Abolishes homooligomerization. FT {ECO:0000269|PubMed:15641782}. FT MUTAGEN 27 27 L->A: Abolishes homooligomerization. FT {ECO:0000269|PubMed:15641782}. FT MUTAGEN 36 36 Y->A: Abolishes interaction with PYDC1. FT {ECO:0000269|PubMed:18362139}. FT MUTAGEN 40 40 P->A: Abolishes homooligomerization. FT {ECO:0000269|PubMed:15641782}. FT MUTAGEN 41 41 R->A,Q,W: Abolishes homooligomerization. FT {ECO:0000269|PubMed:15641782}. FT MUTAGEN 45 45 L->A: Abolishes homooligomerization. FT {ECO:0000269|PubMed:15641782}. FT MUTAGEN 47 47 M->A,N,Q: Abolishes homooligomerization. FT {ECO:0000269|PubMed:15641782}. FT MUTAGEN 48 48 D->A,K: Abolishes homooligomerization. FT {ECO:0000269|PubMed:15641782, FT ECO:0000269|PubMed:18362139}. FT MUTAGEN 48 48 D->A: Abolishes interaction with PYDC1. FT {ECO:0000269|PubMed:15641782, FT ECO:0000269|PubMed:18362139}. FT MUTAGEN 52 52 L->A: Abolishes homooligomerization. FT {ECO:0000269|PubMed:15641782}. FT MUTAGEN 56 56 L->A: Abolishes homooligomerization. FT {ECO:0000269|PubMed:15641782}. FT MUTAGEN 62 62 E->A: Abolishes homooligomerization. FT {ECO:0000269|PubMed:15641782}. FT MUTAGEN 67 67 E->A: Abolishes homooligomerization. FT {ECO:0000269|PubMed:15641782}. FT MUTAGEN 68 68 L->A: Abolishes homooligomerization. FT {ECO:0000269|PubMed:15641782}. FT MUTAGEN 72 72 V->A: Abolishes homooligomerization. FT {ECO:0000269|PubMed:15641782}. FT MUTAGEN 76 76 M->A: Abolishes homooligomerization. FT {ECO:0000269|PubMed:15641782}. FT HELIX 3 14 {ECO:0000244|PDB:1UCP}. FT HELIX 17 26 {ECO:0000244|PDB:1UCP}. FT TURN 27 29 {ECO:0000244|PDB:1UCP}. FT STRAND 34 36 {ECO:0000244|PDB:1UCP}. FT HELIX 41 46 {ECO:0000244|PDB:1UCP}. FT HELIX 49 58 {ECO:0000244|PDB:1UCP}. FT HELIX 62 75 {ECO:0000244|PDB:1UCP}. FT HELIX 80 90 {ECO:0000244|PDB:1UCP}. FT HELIX 117 126 {ECO:0000244|PDB:2KN6}. FT HELIX 129 135 {ECO:0000244|PDB:2KN6}. FT TURN 136 140 {ECO:0000244|PDB:2KN6}. FT HELIX 143 150 {ECO:0000244|PDB:2KN6}. FT HELIX 155 164 {ECO:0000244|PDB:2KN6}. FT HELIX 166 168 {ECO:0000244|PDB:2KN6}. FT HELIX 171 184 {ECO:0000244|PDB:2KN6}. FT HELIX 186 193 {ECO:0000244|PDB:2KN6}. SQ SEQUENCE 195 AA; 21627 MW; 455987286586F46A CRC64; MGRARDAILD ALENLTAEEL KKFKLKLLSV PLREGYGRIP RGALLSMDAL DLTDKLVSFY LETYGAELTA NVLRDMGLQE MAGQLQAATH QGSGAAPAGI QAPPQSAAKP GLHFIDQHRA ALIARVTNVE WLLDALYGKV LTDEQYQAVR AEPTNPSKMR KLFSFTPAWN WTCKDLLLQA LRESQSYLVE DLERS // ID B0V1H4_DANRE Unreviewed; 965 AA. AC B0V1H4; DT 08-APR-2008, integrated into UniProtKB/TrEMBL. DT 08-APR-2008, sequence version 1. DT 20-JUN-2018, entry version 88. DE SubName: Full=Guanylate-binding protein 3 {ECO:0000313|Ensembl:ENSDARP00000118385}; GN Name=gbp3 {ECO:0000313|Ensembl:ENSDARP00000118385, GN ECO:0000313|ZFIN:ZDB-GENE-070912-176}; OS Danio rerio (Zebrafish) (Brachydanio rerio). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes; OC Cyprinidae; Danio. OX NCBI_TaxID=7955 {ECO:0000313|Ensembl:ENSDARP00000118385, ECO:0000313|Proteomes:UP000000437}; RN [1] {ECO:0000313|Ensembl:ENSDARP00000009470} RP IDENTIFICATION. RC STRAIN=Tuebingen {ECO:0000313|Ensembl:ENSDARP00000009470}; RG Ensembl; RL Submitted (FEB-2012) to UniProtKB. RN [2] {ECO:0000213|PDB:4IRL} RP X-RAY CRYSTALLOGRAPHY (1.47 ANGSTROMS) OF 873-965. RX PubMed=23908027; DOI=10.1107/S1744309113015558; RA Jin T., Huang M., Smith P., Jiang J., Xiao T.S.; RT "Structure of the caspase-recruitment domain from a zebrafish RT guanylate-binding protein."; RL Acta Crystallogr. F Struct. Biol. Commun. 69:855-860(2013). RN [3] {ECO:0000313|Ensembl:ENSDARP00000118385, ECO:0000313|Proteomes:UP000000437} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Tuebingen {ECO:0000313|Ensembl:ENSDARP00000118385, RC ECO:0000313|Proteomes:UP000000437}; RX PubMed=23594743; DOI=10.1038/nature12111; RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., RA Muffato M., Collins J.E., Humphray S., McLaren K., Matthews L., RA McLaren S., Sealy I., Caccamo M., Churcher C., Scott C., Barrett J.C., RA Koch R., Rauch G.J., White S., Chow W., Kilian B., Quintais L.T., RA Guerra-Assuncao J.A., Zhou Y., Gu Y., Yen J., Vogel J.H., Eyre T., RA Redmond S., Banerjee R., Chi J., Fu B., Langley E., Maguire S.F., RA Laird G.K., Lloyd D., Kenyon E., Donaldson S., Sehra H., RA Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M., RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J., RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G., RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P., RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., RA Clark S., Pelan S., Griffiths G., Smith M., Glithero R., Howden P., RA Barker N., Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., RA Lovell J., Beasley H., Henderson C., Gordon D., Auger K., Wright D., RA Collins J., Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., RA Leongamornlert D., McGuire S., Gilderthorp R., Griffiths C., RA Manthravadi D., Nichol S., Barker G., Whitehead S., Kay M., Brown J., RA Murnane C., Gray E., Humphries M., Sycamore N., Barker D., RA Saunders D., Wallis J., Babbage A., Hammond S., RA Mashreghi-Mohammadi M., Barr L., Martin S., Wray P., Ellington A., RA Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J., RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E., RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., RA Bird C., Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., RA Eser C., Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., RA Konantz M., Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., RA Raddatz G., Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., RA Yang F., Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., RA Searle S.M., Enright A., Geisler R., Plasterk R.H., Lee C., RA Westerfield M., de Jong P.J., Zon L.I., Postlethwait J.H., RA Nusslein-Volhard C., Hubbard T.J., Roest Crollius H., Rogers J., RA Stemple D.L.; RT "The zebrafish reference genome sequence and its relationship to the RT human genome."; RL Nature 496:498-503(2013). RN [4] {ECO:0000313|Ensembl:ENSDARP00000118385} RP IDENTIFICATION. RC STRAIN=Tuebingen {ECO:0000313|Ensembl:ENSDARP00000118385}; RG Ensembl; RL Submitted (AUG-2013) to UniProtKB. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; CR847981; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR PDB; 4IRL; X-ray; 1.47 A; A/B/C=873-965. DR PDBsum; 4IRL; -. DR STRING; 7955.ENSDARP00000118385; -. DR Ensembl; ENSDART00000007074; ENSDARP00000009470; ENSDARG00000003244. DR Ensembl; ENSDART00000143885; ENSDARP00000118385; ENSDARG00000003244. DR ZFIN; ZDB-GENE-070912-176; gbp3. DR eggNOG; KOG3573; Eukaryota. DR eggNOG; ENOG410ZQIE; LUCA. DR GeneTree; ENSGT00730000111912; -. DR HOGENOM; HOG000205300; -. DR TreeFam; TF331602; -. DR Proteomes; UP000000437; Chromosome 2. DR Bgee; ENSDARG00000003244; -. DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW. DR GO; GO:0003924; F:GTPase activity; IEA:InterPro. DR GO; GO:0006954; P:inflammatory response; IEA:InterPro. DR GO; GO:0045087; P:innate immune response; IEA:InterPro. DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro. DR CDD; cd08330; CARD_ASC_NALP1; 1. DR CDD; cd16269; GBP_C; 1. DR InterPro; IPR001315; CARD. DR InterPro; IPR033516; CARD8/ASC/NALP1_CARD. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR025307; FIIND_dom. DR InterPro; IPR030386; G_GB1_RHD3_dom. DR InterPro; IPR037684; GBP_C. DR InterPro; IPR003191; Guanylate-bd/ATL_C. DR InterPro; IPR036543; Guanylate-bd_C_sf. DR InterPro; IPR015894; Guanylate-bd_N. DR InterPro; IPR027417; P-loop_NTPase. DR Pfam; PF00619; CARD; 1. DR Pfam; PF13553; FIIND; 1. DR Pfam; PF02263; GBP; 1. DR Pfam; PF02841; GBP_C; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR SUPFAM; SSF48340; SSF48340; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR PROSITE; PS50209; CARD; 1. DR PROSITE; PS51830; FIIND; 1. DR PROSITE; PS51715; G_GB1_RHD3; 1. PE 1: Evidence at protein level; KW 3D-structure {ECO:0000213|PDB:4IRL}; KW Coiled coil {ECO:0000256|SAM:Coils}; KW Complete proteome {ECO:0000313|Proteomes:UP000000437}; KW GTP-binding {ECO:0000256|SAAS:SAAS01043854}; KW Nucleotide-binding {ECO:0000256|SAAS:SAAS01043854}; KW Proteomics identification {ECO:0000213|PeptideAtlas:B0V1H4}; KW Reference proteome {ECO:0000313|Proteomes:UP000000437}. FT DOMAIN 36 273 GB1/RHD3-type G. FT {ECO:0000259|PROSITE:PS51715}. FT DOMAIN 588 868 FIIND. {ECO:0000259|PROSITE:PS51830}. FT DOMAIN 874 958 CARD. {ECO:0000259|PROSITE:PS50209}. FT COILED 461 516 {ECO:0000256|SAM:Coils}. SQ SEQUENCE 965 AA; 110340 MW; 0ED9CF562EFAD1A1 CRC64; MAFGVAMFAP VCLIENDGFG KLSVKKQAKD ILDRIIEPVV VVSVVGPHRT GKSYLVNLLA GLQTGFSLGY TIESETKGIW MWCIPHPTKK GHTLVLLDTE GLGDVQEKEK NDKWIFCLAV LLSSVLVYNS LGVIDDEAVE KLHYVTELPE NIRVKAEGDE DESAEFMHVF PSFVWAVQDF DLEFEIEDEW MTSDEYLESA LKLKKGHSLG TQRYNLPRRC LCEFFAQKKC FLFPRPAYRK YMRRLEDLSD ETLDSRFLHQ AHTFCSYIYD NAQPKTVRGH TITGTALGNL AEIYVEAISS GNVICLENAV VSLAKIQNVR AVDQARQIYK EEMLRMAQPP LDPDQLSRIH TLAEEKAIKV FINMSFSDKD QIYQKELMEK IHHEYQHMCL QNHQAFLMQC RKVLEYSFYP LELKISDGSY LRPGGYRQYR ALLNQLISDY RARTESQIKH EEALWMFLQG KEDVGNQILQ ADESLSAAEQ EKEVQILKNE ILQQHQRGLE EQKHLEEQII QQMKRNQEKI RRDDDQALKA KHKHEEASWM IWKGNKDVGN KIVQADESLS AVEQEKEGKS LGSPPRAESS TGQPTSESAE EFTPELIQTV DEDKHKNTYR FVSPHAGQFQ CSLTSLVFVM DGEGEVLYRV VSWDPRLLDG LGQIQPVGPL YDIDCFNGSI SRLHLPHCEI FSEGDNMDGL AVAHFTAGNI EIIQPIKVTE THVMIDIRDL SLFGLLWMKI FSPPISGQVL LFLRTLPVEE REKILNVHLL PGNIPVPEVQ LCHRDKKYIE TTSKCQLFFE REYSLCCQPE NFQVQPTSEI FDHSNFGPNY HPTFEVFLGV HVREVGLAIL DKAENGREVW SRQRILLTAP SQGVEDHRLT PGSEFVDALR GDLIQKVSSV MAIADSLMSE RMITDELYNE VHNADTNQRK MRLLFRALDS GGASVKAEFY RLLMENEPRL VHELESRHSE SSGPQ // ID BCL10_HUMAN Reviewed; 233 AA. AC O95999; Q5VUF1; DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 18-JUL-2018, entry version 168. DE RecName: Full=B-cell lymphoma/leukemia 10; DE AltName: Full=B-cell CLL/lymphoma 10; DE Short=Bcl-10; DE AltName: Full=CARD-containing molecule enhancing NF-kappa-B; DE AltName: Full=CARD-like apoptotic protein; DE Short=hCLAP; DE AltName: Full=CED-3/ICH-1 prodomain homologous E10-like regulator; DE Short=CIPER; DE AltName: Full=Cellular homolog of vCARMEN; DE Short=cCARMEN; DE AltName: Full=Cellular-E10; DE Short=c-E10; DE AltName: Full=Mammalian CARD-containing adapter molecule E10; DE Short=mE10; GN Name=BCL10; Synonyms=CIPER, CLAP; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], INVOLVEMENT IN MALTOMA, AND VARIANTS RP ILE-52; GLY-58; GLU-210 DEL AND PHE-218. RC TISSUE=Lymphoma; RX PubMed=9989495; DOI=10.1016/S0092-8674(00)80957-5; RA Willis T.G., Jadayel D.M., Du M.-Q., Peng H., Perry A.R., RA Abdul-Rauf M., Price H., Karran L., Majekodunmi O., Wlodarska I., RA Pan L., Crook T., Hamoudi R., Isaacson P., Dyer M.J.S.; RT "Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and RT mutated in multiple tumor types."; RL Cell 96:35-45(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND MUTAGENESIS OF LEU-41 AND GLY-78. RX PubMed=10187770; DOI=10.1074/jbc.274.15.9955; RA Koseki T., Inohara N., Chen S., Carrio R., Merino J., Hottiger M.O., RA Nabel G.J., Nunez G.; RT "CIPER, a novel NF kappaB-activating protein containing a caspase RT recruitment domain with homology to Herpesvirus-2 protein E10."; RL J. Biol. Chem. 274:9955-9961(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=10187771; DOI=10.1074/jbc.274.15.9962; RA Thome M., Martinon F., Hofmann K., Rubio V., Steiner V., Schneider P., RA Mattmann C., Tschopp J.; RT "Equine herpesvirus-2 E10 gene product, but not its cellular RT homologue, activates NF-kappaB transcription factor and c-Jun N- RT terminal kinase."; RL J. Biol. Chem. 274:9962-9968(1999). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], AND MUTAGENESIS OF LEU-28; LEU-41; ILE-46; RP LEU-47; GLU-53 AND ILE-55. RX PubMed=10187815; DOI=10.1074/jbc.274.15.10287; RA Yan M., Lee J., Schilbach S., Goddard A., Dixit V.M.; RT "mE10, a novel caspase recruitment domain-containing proapoptotic RT molecule."; RL J. Biol. Chem. 274:10287-10292(1999). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=10364242; DOI=10.1074/jbc.274.25.17946; RA Srinivasula S.M., Ahmad M., Lin J.-H., Poyet J.-L., RA Fernandes-Alnemri T., Tsichlis P.N., Alnemri E.S.; RT "CLAP, a novel caspase recruitment domain-containing protein in the RT tumor necrosis factor receptor pathway, regulates NF-kappaB activation RT and apoptosis."; RL J. Biol. Chem. 274:17946-17954(1999). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Spleen; RX PubMed=10400625; DOI=10.1074/jbc.274.29.20127; RA Costanzo A., Guiet C., Vito P.; RT "c-E10 is a caspase-recruiting domain-containing protein that RT interacts with components of death receptors signaling pathway and RT activates nuclear factor-kappaB."; RL J. Biol. Chem. 274:20127-20132(1999). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANTS SER-5; GLU-16; RP GLU-31; ARG-57; LYS-64; GLU-101; PRO-134; ALA-168; SER-174; GLU-213 RP AND ILE-230. RX PubMed=10319863; DOI=10.1038/8767; RA Zhang Q., Siebert R., Yan M., Hinzmann B., Cui X., Xue L., RA Rakestraw K.M., Naeve C.W., Beckmann G., Weisenburger D.D., RA Sanger W.G., Nowotny H., Vesely M., Callet-Bauchu E., Salles G., RA Dixit V.M., Rosenthal A., Schlegelberger B., Morris S.W.; RT "Inactivating mutations and overexpression of BCL10, a caspase RT recruitment domain-containing gene, in MALT lymphoma with RT t(1;14)(p22;q32)."; RL Nat. Genet. 22:63-68(1999). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Eye; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [12] RP PHOSPHORYLATION. RX PubMed=11466612; DOI=10.1038/sj.onc.1204576; RA Yui D., Yoneda T., Oono K., Katayama T., Imaizumi K., Tohyama M.; RT "Interchangeable binding of Bcl10 to TRAF2 and cIAPs regulates RT apoptosis signaling."; RL Oncogene 20:4317-4323(2001). RN [13] RP IDENTIFICATION IN A MEMBRANE RAFT COMPLEX, AND SUBCELLULAR LOCATION. RX PubMed=17287217; DOI=10.1074/jbc.M609157200; RA Ohnuma K., Uchiyama M., Yamochi T., Nishibashi K., Hosono O., RA Takahashi N., Kina S., Tanaka H., Lin X., Dang N.H., Morimoto C.; RT "Caveolin-1 triggers T-cell activation via CD26 in association with RT CARMA1."; RL J. Biol. Chem. 282:10117-10131(2007). RN [14] RP PHOSPHORYLATION BY IKBKB/IKKB, AND MUTAGENESIS OF 81-THR--SER-85. RX PubMed=17213322; DOI=10.1073/pnas.0606982104; RA Lobry C., Lopez T., Israel A., Weil R.; RT "Negative feedback loop in T cell activation through IkappaB kinase- RT induced phosphorylation and degradation of Bcl10."; RL Proc. Natl. Acad. Sci. U.S.A. 104:908-913(2007). RN [15] RP FUNCTION, AND MUTAGENESIS OF ARG-228. RX PubMed=18264101; DOI=10.1038/ni1568; RA Rebeaud F., Hailfinger S., Posevitz-Fejfar A., Tapernoux M., Moser R., RA Rueda D., Gaide O., Guzzardi M., Iancu E.M., Rufer N., Fasel N., RA Thome M.; RT "The proteolytic activity of the paracaspase MALT1 is key in T cell RT activation."; RL Nat. Immunol. 9:272-281(2008). RN [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [19] RP FUNCTION, AND INVOLVEMENT IN IMD37. RX PubMed=25365219; DOI=10.1172/JCI77493; RA Torres J.M., Martinez-Barricarte R., Garcia-Gomez S., Mazariegos M.S., RA Itan Y., Boisson B., Rholvarez R., Jimenez-Reinoso A., Del Pino L., RA Rodriguez-Pena R., Ferreira A., Hernandez-Jimenez E., Toledano V., RA Cubillos-Zapata C., Diaz-Almiron M., Lopez-Collazo E., RA Unzueta-Roch J.L., Sanchez-Ramon S., Regueiro J.R., Lopez-Granados E., RA Casanova J.L., Perez de Diego R.; RT "Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic RT immunity."; RL J. Clin. Invest. 124:5239-5248(2014). RN [20] RP SUBUNIT. RX PubMed=27113748; DOI=10.15252/embr.201642109; RA Afonina I.S., Van Nuffel E., Baudelet G., Driege Y., Kreike M., RA Staal J., Beyaert R.; RT "The paracaspase MALT1 mediates CARD14-induced signaling in RT keratinocytes."; RL EMBO Rep. 17:914-927(2016). RN [21] RP INTERACTION WITH CARD11 AND MALT1. RX PubMed=28628108; DOI=10.1038/ng.3898; RA Ma C.A., Stinson J.R., Zhang Y., Abbott J.K., Weinreich M.A., RA Hauk P.J., Reynolds P.R., Lyons J.J., Nelson C.G., Ruffo E., RA Dorjbal B., Glauzy S., Yamakawa N., Arjunaraja S., Voss K., RA Stoddard J., Niemela J., Zhang Y., Rosenzweig S.D., McElwee J.J., RA DiMaggio T., Matthews H.F., Jones N., Stone K.D., Palma A., RA Oleastro M., Prieto E., Bernasconi A.R., Dubra G., Danielian S., RA Zaiat J., Marti M.A., Kim B., Cooper M.A., Romberg N., Meffre E., RA Gelfand E.W., Snow A.L., Milner J.D.; RT "Germline hypomorphic CARD11 mutations in severe atopic disease."; RL Nat. Genet. 49:1192-1201(2017). RN [22] RP VARIANTS SER-5; MET-162 AND GLU-213. RX PubMed=10582682; RA Lee S.H., Shin M.S., Kim H.S., Park W.S., Kim S.Y., Lee H.K., RA Park J.Y., Oh R.R., Jang J.J., Park K.M., Han J.Y., Kang C.S., RA Lee J.Y., Yoo N.J.; RT "Point mutations and deletions of the Bcl10 gene in solid tumors and RT malignant lymphomas."; RL Cancer Res. 59:5674-5677(1999). RN [23] RP VARIANTS SER-5; GLN-45; GLN-58; SER-93; VAL-153; GLU-213 AND PHE-218. RX PubMed=10380921; DOI=10.1016/S0092-8674(02)09765-9; RA Apostolou S., de Rienzo A., Murthy S.S., Jhanwar S.C., Testa J.R.; RT "Absence of BCL10 mutations in human malignant mesothelioma."; RL Cell 97:684-686(1999). CC -!- FUNCTION: Involved in adaptive immune response (PubMed:25365219). CC Promotes apoptosis, pro-caspase-9 maturation and activation of NF- CC kappa-B via NIK and IKK. May be an adapter protein between CC upstream TNFR1-TRADD-RIP complex and the downstream NIK-IKK-IKAP CC complex. Is a substrate for MALT1 (PubMed:18264101). CC {ECO:0000269|PubMed:18264101, ECO:0000269|PubMed:25365219}. CC -!- SUBUNIT: Found in a membrane raft complex, at least composed of CC BCL10, CARD11, DPP4 and IKBKB. Self-associates by CARD-CARD CC interaction and forms a tight complex with MALT1. Interacts with CC other CARD-proteins such as CARD9, CARD10, CARD11 and CARD14. CC Forms a complex with CARD14 and MALT1; resulting in the formation CC of a CBM (CARD14-BCL10-MALT1) complex (PubMed:27113748). Binds CC caspase-9 with its C-terminal domain. Interacts with TRAF2 and CC BIRC2/c-IAP2. Interacts with PELI2 and SOCS3; these interactions CC may be mutually exclusive (By similarity). Interacts with CARD11 CC and MALT1; as part of a CBM (CARD11-BCL10-MALT1) complex involved CC in NF-kappa-B activation. {ECO:0000250|UniProtKB:Q9Z0H7, CC ECO:0000269|PubMed:27113748}. CC -!- INTERACTION: CC Self; NbExp=4; IntAct=EBI-958922, EBI-958922; CC P31749:AKT1; NbExp=5; IntAct=EBI-958922, EBI-296087; CC P20749:BCL3; NbExp=3; IntAct=EBI-958922, EBI-958997; CC Q9BXL7:CARD11; NbExp=7; IntAct=EBI-958922, EBI-7006141; CC Q96LW7:CARD19; NbExp=4; IntAct=EBI-958922, EBI-7443927; CC Q9H257:CARD9; NbExp=6; IntAct=EBI-958922, EBI-751319; CC Q9Y2V7:COG6; NbExp=4; IntAct=EBI-958922, EBI-3866319; CC Q66677:E10 (xeno); NbExp=2; IntAct=EBI-958922, EBI-11709474; CC Q9Y6K9:IKBKG; NbExp=7; IntAct=EBI-958922, EBI-81279; CC Q9UDY8:MALT1; NbExp=18; IntAct=EBI-958922, EBI-1047372; CC Q05513:PRKCZ; NbExp=3; IntAct=EBI-958922, EBI-295351; CC Q12933:TRAF2; NbExp=8; IntAct=EBI-958922, EBI-355744; CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region CC {ECO:0000269|PubMed:17287217}. Membrane raft CC {ECO:0000269|PubMed:17287217}. Note=Appears to have a perinuclear, CC compact and filamentous pattern of expression. Also found in the CC nucleus of several types of tumor cells. Colocalized with DPP4 in CC membrane rafts. CC -!- TISSUE SPECIFICITY: Ubiquitous. CC -!- PTM: Phosphorylated. Phosphorylation results in dissociation from CC TRAF2 and binding to BIRC2/c-IAP2. Phosphorylated by IKBKB/IKKB. CC {ECO:0000269|PubMed:11466612, ECO:0000269|PubMed:17213322}. CC -!- DISEASE: Note=A chromosomal aberration involving BCL10 is CC recurrent in low-grade mucosa-associated lymphoid tissue (MALT CC lymphoma). Translocation t(1;14)(p22;q32). Although the BCL10/IgH CC translocation leaves the coding region of BCL10 intact, frequent CC BCL10 mutations could be attributed to the Ig somatic CC hypermutation mechanism resulting in nucleotide transitions. CC -!- DISEASE: Immunodeficiency 37 (IMD37) [MIM:616098]: A form of CC primary combined immunodeficiency, a group of disorders CC characterized by severe recurrent infections, with normal numbers CC or an absence of T and B lymphocytes, and impaired cellular and CC humoral immunity. IMD37 is characterized by hypogammaglobulinemia CC without lymphopenia, but with profoundly reduced memory B cells CC and memory T cells, and increased numbers of circulating naive CC lymphocytes. Inheritance is autosomal recessive. CC {ECO:0000269|PubMed:25365219}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Lymphoma, mucosa-associated lymphoid type (MALTOMA) CC [MIM:137245]: A subtype of non-Hodgkin lymphoma, originating in CC mucosa-associated lymphoid tissue. MALT lymphomas occur most CC commonly in the gastro-intestinal tract but have been described in CC a variety of extranodal sites including the ocular adnexa, CC salivary gland, thyroid, lung, thymus, and breast. Histologically, CC they are characterized by an infiltrate of small to medium-sized CC lymphocytes with abundant cytoplasm and irregularly shaped nuclei. CC Scattered transformed blasts (large cells) also are present. Non- CC malignant reactive follicles are observed frequently. A pivotal CC feature is the presence of lymphoepithelial lesions, with invasion CC and partial destruction of mucosal glands and crypts by aggregates CC of tumor cells. {ECO:0000269|PubMed:9989495}. Note=The disease is CC caused by mutations affecting the gene represented in this entry. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/BCL10ID222ch1p22.html"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AJ006288; CAA06955.1; -; mRNA. DR EMBL; AF057700; AAD15800.1; -; mRNA. DR EMBL; AF100338; AAD16428.1; -; mRNA. DR EMBL; AF127386; AAD32597.1; -; mRNA. DR EMBL; AF134395; AAD39147.1; -; mRNA. DR EMBL; AF105066; AAF06894.1; -; mRNA. DR EMBL; AF082283; AAC99767.1; -; mRNA. DR EMBL; AF097732; AAD24918.1; -; Genomic_DNA. DR EMBL; AK291346; BAF84035.1; -; mRNA. DR EMBL; AL590113; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471097; EAW73208.1; -; Genomic_DNA. DR EMBL; BC053617; AAH53617.1; -; mRNA. DR CCDS; CCDS704.1; -. DR RefSeq; NP_003912.1; NM_003921.4. DR UniGene; Hs.193516; -. DR PDB; 2MB9; NMR; -; A=1-115. DR PDB; 6BZE; EM; 4.00 A; A/B/C/D/E/F/G/H=10-115. DR PDBsum; 2MB9; -. DR PDBsum; 6BZE; -. DR ProteinModelPortal; O95999; -. DR SMR; O95999; -. DR BioGrid; 114429; 65. DR CORUM; O95999; -. DR DIP; DIP-29740N; -. DR IntAct; O95999; 42. DR MINT; O95999; -. DR STRING; 9606.ENSP00000271015; -. DR iPTMnet; O95999; -. DR PhosphoSitePlus; O95999; -. DR BioMuta; BCL10; -. DR EPD; O95999; -. DR PaxDb; O95999; -. DR PeptideAtlas; O95999; -. DR PRIDE; O95999; -. DR ProteomicsDB; 51178; -. DR DNASU; 8915; -. DR Ensembl; ENST00000370580; ENSP00000359612; ENSG00000142867. DR GeneID; 8915; -. DR KEGG; hsa:8915; -. DR UCSC; uc021opd.3; human. DR CTD; 8915; -. DR DisGeNET; 8915; -. DR EuPathDB; HostDB:ENSG00000142867.12; -. DR GeneCards; BCL10; -. DR HGNC; HGNC:989; BCL10. DR HPA; CAB001944; -. DR HPA; HPA017925; -. DR MalaCards; BCL10; -. DR MIM; 137245; phenotype. DR MIM; 603517; gene. DR MIM; 616098; phenotype. DR neXtProt; NX_O95999; -. DR OpenTargets; ENSG00000142867; -. DR PharmGKB; PA25299; -. DR eggNOG; ENOG410IVMM; Eukaryota. DR eggNOG; ENOG4111JRA; LUCA. DR GeneTree; ENSGT00490000043442; -. DR HOGENOM; HOG000008671; -. DR HOVERGEN; HBG050680; -. DR InParanoid; O95999; -. DR KO; K07368; -. DR OMA; RHYLCDK; -. DR OrthoDB; EOG091G0UTQ; -. DR PhylomeDB; O95999; -. DR TreeFam; TF328636; -. DR Reactome; R-HSA-1169091; Activation of NF-kappaB in B cells. DR Reactome; R-HSA-202424; Downstream TCR signaling. DR Reactome; R-HSA-2871837; FCERI mediated NF-kB activation. DR Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling. DR Reactome; R-HSA-8866654; E3 ubiquitin ligases ubiquitinate target proteins. DR SignaLink; O95999; -. DR SIGNOR; O95999; -. DR ChiTaRS; BCL10; human. DR GeneWiki; BCL10; -. DR GenomeRNAi; 8915; -. DR PRO; PR:O95999; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; ENSG00000142867; -. DR CleanEx; HS_BCL10; -. DR ExpressionAtlas; O95999; baseline and differential. DR Genevisible; O95999; HS. DR GO; GO:0032449; C:CBM complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005881; C:cytoplasmic microtubule; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0001772; C:immunological synapse; IEA:Ensembl. DR GO; GO:0005764; C:lysosome; IDA:UniProtKB. DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB. DR GO; GO:0051059; F:NF-kappaB binding; IDA:UniProtKB. DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL. DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB. DR GO; GO:0043422; F:protein kinase B binding; IPI:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IDA:UniProtKB. DR GO; GO:0043621; F:protein self-association; IPI:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB. DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0002250; P:adaptive immune response; IMP:UniProtKB. DR GO; GO:0001783; P:B cell apoptotic process; IEA:Ensembl. DR GO; GO:0008219; P:cell death; IDA:UniProtKB. DR GO; GO:0006968; P:cellular defense response; IEA:Ensembl. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB. DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome. DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl. DR GO; GO:0016064; P:immunoglobulin mediated immune response; IEA:Ensembl. DR GO; GO:0045087; P:innate immune response; IEP:UniProtKB. DR GO; GO:0042226; P:interleukin-6 biosynthetic process; NAS:UniProtKB. DR GO; GO:0042109; P:lymphotoxin A biosynthetic process; NAS:UniProtKB. DR GO; GO:0002906; P:negative regulation of mature B cell apoptotic process; IDA:UniProtKB. DR GO; GO:0001843; P:neural tube closure; ISS:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IEA:Ensembl. DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IDA:UniProtKB. DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEP:UniProtKB. DR GO; GO:0045416; P:positive regulation of interleukin-8 biosynthetic process; IMP:UniProtKB. DR GO; GO:0032765; P:positive regulation of mast cell cytokine production; NAS:UniProtKB. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB. DR GO; GO:0042327; P:positive regulation of phosphorylation; IDA:UniProtKB. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB. DR GO; GO:0050870; P:positive regulation of T cell activation; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0051259; P:protein complex oligomerization; IPI:UniProtKB. DR GO; GO:0051291; P:protein heterooligomerization; IEA:Ensembl. DR GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB. DR GO; GO:0016567; P:protein ubiquitination; TAS:Reactome. DR GO; GO:0050856; P:regulation of T cell receptor signaling pathway; IEA:Ensembl. DR GO; GO:0032094; P:response to food; IDA:UniProtKB. DR GO; GO:0009620; P:response to fungus; IEA:Ensembl. DR GO; GO:0002237; P:response to molecule of bacterial origin; IEP:UniProtKB. DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; TAS:Reactome. DR GO; GO:0070231; P:T cell apoptotic process; IEA:Ensembl. DR GO; GO:0050852; P:T cell receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0002224; P:toll-like receptor signaling pathway; IC:UniProtKB. DR InterPro; IPR033238; BCL10/E10. DR InterPro; IPR001315; CARD. DR InterPro; IPR011029; DEATH-like_dom_sf. DR PANTHER; PTHR34920; PTHR34920; 1. DR Pfam; PF00619; CARD; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR PROSITE; PS50209; CARD; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Apoptosis; Chromosomal rearrangement; KW Complete proteome; Cytoplasm; Disease mutation; Immunity; Membrane; KW Phosphoprotein; Reference proteome; Tumor suppressor. FT CHAIN 1 233 B-cell lymphoma/leukemia 10. FT /FTId=PRO_0000144074. FT DOMAIN 13 101 CARD. {ECO:0000255|PROSITE- FT ProRule:PRU00046}. FT MOD_RES 1 1 N-acetylmethionine. FT {ECO:0000244|PubMed:19413330}. FT MOD_RES 138 138 Phosphoserine. FT {ECO:0000244|PubMed:21406692}. FT VARIANT 5 5 A -> S (found in a MALT lymphoma sample; FT unknown pathological significance; FT dbSNP:rs12037217). FT {ECO:0000269|PubMed:10319863, FT ECO:0000269|PubMed:10380921, FT ECO:0000269|PubMed:10582682}. FT /FTId=VAR_013208. FT VARIANT 16 16 V -> E (found in a MALT lymphoma sample; FT unknown pathological significance). FT {ECO:0000269|PubMed:10319863}. FT /FTId=VAR_013209. FT VARIANT 31 31 K -> E (found in a MALT lymphoma sample; FT unknown pathological significance). FT {ECO:0000269|PubMed:10319863}. FT /FTId=VAR_013210. FT VARIANT 45 45 K -> Q. {ECO:0000269|PubMed:10380921}. FT /FTId=VAR_013211. FT VARIANT 52 52 T -> I (found in a mesothelioma sample; FT unknown pathological significance). FT {ECO:0000269|PubMed:9989495}. FT /FTId=VAR_013212. FT VARIANT 57 57 C -> R (found in a MALT lymphoma sample; FT unknown pathological significance). FT {ECO:0000269|PubMed:10319863}. FT /FTId=VAR_013213. FT VARIANT 58 58 R -> G (found in a germ cell tumor FT sample; unknown pathological FT significance; dbSNP:rs121918314). FT {ECO:0000269|PubMed:9989495}. FT /FTId=VAR_013214. FT VARIANT 58 58 R -> Q. {ECO:0000269|PubMed:10380921}. FT /FTId=VAR_013215. FT VARIANT 64 64 R -> K (found in a MALT lymphoma sample; FT unknown pathological significance). FT {ECO:0000269|PubMed:10319863}. FT /FTId=VAR_013216. FT VARIANT 93 93 N -> S. {ECO:0000269|PubMed:10380921}. FT /FTId=VAR_013217. FT VARIANT 101 101 D -> E (found in a MALT lymphoma sample; FT unknown pathological significance). FT {ECO:0000269|PubMed:10319863}. FT /FTId=VAR_013218. FT VARIANT 134 134 S -> P (found in a MALT lymphoma sample; FT unknown pathological significance). FT {ECO:0000269|PubMed:10319863}. FT /FTId=VAR_013219. FT VARIANT 153 153 M -> V. {ECO:0000269|PubMed:10380921}. FT /FTId=VAR_013220. FT VARIANT 162 162 T -> M (found in a testicular teratoma FT sample; somatic mutation; FT dbSNP:rs200837308). FT {ECO:0000269|PubMed:10582682}. FT /FTId=VAR_077898. FT VARIANT 168 168 T -> A (found in a MALT lymphoma sample; FT unknown pathological significance). FT {ECO:0000269|PubMed:10319863}. FT /FTId=VAR_013221. FT VARIANT 174 174 L -> S (found in a MALT lymphoma sample; FT unknown pathological significance). FT {ECO:0000269|PubMed:10319863}. FT /FTId=VAR_013222. FT VARIANT 210 210 Missing (found in a follicular lymphoma FT sample; unknown pathological FT significance). FT {ECO:0000269|PubMed:9989495}. FT /FTId=VAR_013223. FT VARIANT 213 213 G -> E (found in a MALT lymphoma sample; FT unknown pathological significance; FT dbSNP:rs3768235). FT {ECO:0000269|PubMed:10319863, FT ECO:0000269|PubMed:10380921, FT ECO:0000269|PubMed:10582682}. FT /FTId=VAR_013224. FT VARIANT 218 218 S -> F (found in a germ cell tumor and FT other cancer cell lines; unknown FT pathological significance). FT {ECO:0000269|PubMed:10380921, FT ECO:0000269|PubMed:9989495}. FT /FTId=VAR_013225. FT VARIANT 230 230 V -> I (found in a MALT lymphoma sample; FT unknown pathological significance). FT {ECO:0000269|PubMed:10319863}. FT /FTId=VAR_013226. FT MUTAGEN 28 28 L->A: Abolishes cell death-inducing FT capability. FT {ECO:0000269|PubMed:10187815}. FT MUTAGEN 41 41 L->A: Abolishes cell death-inducing FT capability. {ECO:0000269|PubMed:10187770, FT ECO:0000269|PubMed:10187815}. FT MUTAGEN 41 41 L->Q: Abolishes NF-kappa-B activation and FT homo/hetero-dimerization. FT {ECO:0000269|PubMed:10187770, FT ECO:0000269|PubMed:10187815}. FT MUTAGEN 46 46 I->A: Abolishes cell death-inducing FT capability. FT {ECO:0000269|PubMed:10187815}. FT MUTAGEN 47 47 L->A: Abolishes cell death-inducing FT capability. FT {ECO:0000269|PubMed:10187815}. FT MUTAGEN 53 53 E->A: Abolishes cell death-inducing FT capability. FT {ECO:0000269|PubMed:10187815}. FT MUTAGEN 55 55 I->A: Abolishes cell death-inducing FT capability. FT {ECO:0000269|PubMed:10187815}. FT MUTAGEN 78 78 G->R: Abolishes NF-kappa-B activation. FT {ECO:0000269|PubMed:10187770}. FT MUTAGEN 81 85 TLVES->ALVEA: Complete loss of FT IKBKB/IKKB-mediated phosphorylation. FT {ECO:0000269|PubMed:17213322}. FT MUTAGEN 228 228 R->G: Abolishes MALT1-mediated cleavage. FT {ECO:0000269|PubMed:18264101}. FT MUTAGEN 231 231 S->A: Promotes NF-kappa-B activation. FT HELIX 11 14 {ECO:0000244|PDB:2MB9}. FT HELIX 17 28 {ECO:0000244|PDB:2MB9}. FT TURN 29 31 {ECO:0000244|PDB:2MB9}. FT STRAND 32 38 {ECO:0000244|PDB:2MB9}. FT HELIX 39 42 {ECO:0000244|PDB:2MB9}. FT HELIX 49 53 {ECO:0000244|PDB:2MB9}. FT TURN 54 57 {ECO:0000244|PDB:2MB9}. FT HELIX 61 72 {ECO:0000244|PDB:2MB9}. FT TURN 76 79 {ECO:0000244|PDB:2MB9}. FT HELIX 80 86 {ECO:0000244|PDB:2MB9}. FT STRAND 89 92 {ECO:0000244|PDB:2MB9}. FT HELIX 94 105 {ECO:0000244|PDB:2MB9}. FT HELIX 107 113 {ECO:0000244|PDB:2MB9}. SQ SEQUENCE 233 AA; 26252 MW; F87C97F2B784BA4B CRC64; MEPTAPSLTE EDLTEVKKDA LENLRVYLCE KIIAERHFDH LRAKKILSRE DTEEISCRTS SRKRAGKLLD YLQENPKGLD TLVESIRREK TQNFLIQKIT DEVLKLRNIK LEHLKGLKCS SCEPFPDGAT NNLSRSNSDE SNFSEKLRAS TVMYHPEGES STTPFFSTNS SLNLPVLEVG RTENTIFSST TLPRPGDPGA PPLPPDLQLE EEGTCANSSE MFLPLRSRTV SRQ // ID BIRC2_HUMAN Reviewed; 618 AA. AC Q13490; B4E026; Q16516; Q4TTG0; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 2. DT 18-JUL-2018, entry version 194. DE RecName: Full=Baculoviral IAP repeat-containing protein 2; DE EC=2.3.2.27 {ECO:0000269|PubMed:18082613, ECO:0000269|PubMed:21145488, ECO:0000269|PubMed:21931591, ECO:0000269|PubMed:23453969}; DE AltName: Full=Cellular inhibitor of apoptosis 1; DE Short=C-IAP1 {ECO:0000303|PubMed:8548810}; DE AltName: Full=IAP homolog B; DE AltName: Full=Inhibitor of apoptosis protein 2; DE Short=hIAP-2; DE Short=hIAP2; DE AltName: Full=RING finger protein 48; DE AltName: Full=RING-type E3 ubiquitin transferase BIRC2 {ECO:0000305}; DE AltName: Full=TNFR2-TRAF-signaling complex protein 2; GN Name=BIRC2; Synonyms=API1, MIHB, RNF48; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8548810; DOI=10.1016/0092-8674(95)90149-3; RA Rothe M., Pan M.-G., Henzel W.J., Ayres T.M., Goeddel D.V.; RT "The TNFR2-TRAF signaling complex contains two novel proteins related RT to baculoviral inhibitor of apoptosis proteins."; RL Cell 83:1243-1252(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=8552191; DOI=10.1038/379349a0; RA Liston P., Roy N., Tamai K., Lefebvre C., Baird S., Cherton-Horvat G., RA Farahani R., McLean M., Ikeda J., Mackenzie A., Korneluk R.G.; RT "Suppression of apoptosis in mammalian cells by NAIP and a related RT family of IAP genes."; RL Nature 379:349-353(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Fetal liver; RX PubMed=8643514; DOI=10.1073/pnas.93.10.4974; RA Uren A.G., Pakusch M., Hawkins C.J., Puls K.L., Vaux D.L.; RT "Cloning and expression of apoptosis inhibitory protein homologs that RT function to inhibit apoptosis and/or bind tumor necrosis factor RT receptor-associated factors."; RL Proc. Natl. Acad. Sci. U.S.A. 93:4974-4978(1996). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-453; VAL-506 AND RP SER-549. RG NIEHS SNPs program; RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Thymus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S., RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., RA Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis, and Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BIRC5/SURVIVIN. RX PubMed=15665297; RA Samuel T., Okada K., Hyer M., Welsh K., Zapata J.M., Reed J.C.; RT "cIAP1 Localizes to the nuclear compartment and modulates the cell RT cycle."; RL Cancer Res. 65:210-218(2005). RN [9] RP FUNCTION IN THE UBIQUITINATION OF MXD1/MAD1, AND CATALYTIC ACTIVITY. RX PubMed=18082613; DOI=10.1016/j.molcel.2007.10.027; RA Xu L., Zhu J., Hu X., Zhu H., Kim H.T., LaBaer J., Goldberg A., RA Yuan J.; RT "c-IAP1 cooperates with Myc by acting as a ubiquitin ligase for RT Mad1."; RL Mol. Cell 28:914-922(2007). RN [10] RP REVIEW ON FUNCTION. RX PubMed=18414036; DOI=10.4161/cc.7.8.5783; RA Dubrez-Daloz L., Dupoux A., Cartier J.; RT "IAPs: more than just inhibitors of apoptosis proteins."; RL Cell Cycle 7:1036-1046(2008). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [13] RP REVIEW ON FUNCTION. RX PubMed=20888210; DOI=10.1016/j.ceb.2010.08.025; RA Lopez J., Meier P.; RT "To fight or die - inhibitor of apoptosis proteins at the crossroad of RT innate immunity and death."; RL Curr. Opin. Cell Biol. 22:872-881(2010). RN [14] RP FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE OF THE NEDD8 CONJUGATION RP PATHWAY, AND CATALYTIC ACTIVITY. RX PubMed=21145488; DOI=10.1016/j.molcel.2010.11.011; RA Broemer M., Tenev T., Rigbolt K.T., Hempel S., Blagoev B., Silke J., RA Ditzel M., Meier P.; RT "Systematic in vivo RNAi analysis identifies IAPs as NEDD8-E3 RT ligases."; RL Mol. Cell 40:810-822(2010). RN [15] RP REVIEW ON FUNCTION. RX PubMed=20651737; DOI=10.1038/nrc2889; RA Gyrd-Hansen M., Meier P.; RT "IAPs: from caspase inhibitors to modulators of NF-kappaB, RT inflammation and cancer."; RL Nat. Rev. Cancer 10:561-574(2010). RN [16] RP REVIEW ON FUNCTION. RX PubMed=21447281; RA Damgaard R.B., Gyrd-Hansen M.; RT "Inhibitor of apoptosis (IAP) proteins in regulation of inflammation RT and innate immunity."; RL Discov. Med. 11:221-231(2011). RN [17] RP FUNCTION, INTERACTION WITH E2F1 AND TRAF2, AND SUBCELLULAR LOCATION. RX PubMed=21653699; DOI=10.1074/jbc.M110.191239; RA Cartier J., Berthelet J., Marivin A., Gemble S., Edmond V., RA Plenchette S., Lagrange B., Hammann A., Dupoux A., Delva L., Eymin B., RA Solary E., Dubrez L.; RT "Cellular inhibitor of apoptosis protein-1 (cIAP1) can regulate E2F1 RT transcription factor-mediated control of cyclin transcription."; RL J. Biol. Chem. 286:26406-26417(2011). RN [18] RP ENZYME REGULATION, AND INTERACTION WITH USP19. RX PubMed=21849505; DOI=10.1074/jbc.M111.282020; RA Mei Y., Hahn A.A., Hu S., Yang X.; RT "The USP19 deubiquitinase regulates the stability of c-IAP1 and c- RT IAP2."; RL J. Biol. Chem. 286:35380-35387(2011). RN [19] RP FUNCTION IN THE UBIQUITINATION OF RIPK1; RIPK2; RIPK3 AND RIPK4, RP INTERACTION WITH RIPK1; RIPK2; RIPK3 AND RIPK4, AND CATALYTIC RP ACTIVITY. RX PubMed=21931591; DOI=10.1371/journal.pone.0022356; RA Bertrand M.J., Lippens S., Staes A., Gilbert B., Roelandt R., RA De Medts J., Gevaert K., Declercq W., Vandenabeele P.; RT "cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin RT chains to receptor interacting proteins kinases 1 to 4 (RIP1-4)."; RL PLoS ONE 6:E22356-E22356(2011). RN [20] RP REVIEW ON FUNCTION. RX PubMed=22095281; DOI=10.1038/cdd.2011.163; RA Darding M., Meier P.; RT "IAPs: guardians of RIPK1."; RL Cell Death Differ. 19:58-66(2012). RN [21] RP FUNCTION IN IKBKE UBIQUITINATION, AND CATALYTIC ACTIVITY. RX PubMed=23453969; DOI=10.1016/j.celrep.2013.01.031; RA Zhou A.Y., Shen R.R., Kim E., Lock Y.J., Xu M., Chen Z.J., Hahn W.C.; RT "IKKepsilon-mediated tumorigenesis requires K63-linked RT polyubiquitination by a cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase RT complex."; RL Cell Rep. 3:724-733(2013). RN [22] RP INTERACTION WITH HSP90AB1. RX PubMed=25486457; DOI=10.1016/j.bbamcr.2014.11.026; RA Synoradzki K., Bieganowski P.; RT "Middle domain of human Hsp90 isoforms differentially binds Aha1 in RT human cells and alters Hsp90 activity in yeast."; RL Biochim. Biophys. Acta 1853:445-452(2015). RN [23] RP INTERACTION WITH UBXN1. RX PubMed=25681446; DOI=10.1074/jbc.M114.631689; RA Wang Y.B., Tan B., Mu R., Chang Y., Wu M., Tu H.Q., Zhang Y.C., RA Guo S.S., Qin X.H., Li T., Li W.H., Li A.L., Zhang X.M., Li H.Y.; RT "Ubiquitin-associated domain-containing ubiquitin regulatory X (UBX) RT protein UBXN1 is a negative regulator of nuclear factor kappaB (NF- RT kappaB) signaling."; RL J. Biol. Chem. 290:10395-10405(2015). RN [24] RP STRUCTURE BY NMR OF 266-363. RX PubMed=10404221; DOI=10.1038/10701; RA Hinds M.G., Norton R.S., Vaux D.L., Day C.L.; RT "Solution structure of a baculoviral inhibitor of apoptosis (IAP) RT repeat."; RL Nat. Struct. Biol. 6:648-651(1999). RN [25] RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 260-352 IN COMPLEXES WITH RP ZINC IONS; DIABLO AND CASP9 PEPTIDES, AND SUBUNIT. RX PubMed=19153467; DOI=10.1107/S0907444908039243; RA Kulathila R., Vash B., Sage D., Cornell-Kennon S., Wright K., RA Koehn J., Stams T., Clark K., Price A.; RT "The structure of the BIR3 domain of cIAP1 in complex with the N- RT terminal peptides of SMAC and caspase-9."; RL Acta Crystallogr. D 65:58-66(2009). RN [26] RP STRUCTURE BY NMR OF 435-562, DOMAIN CARD, AND ENZYME REGULATION. RX PubMed=21549626; DOI=10.1016/j.molcel.2011.04.008; RA Lopez J., John S.W., Tenev T., Rautureau G.J., Hinds M.G., RA Francalanci F., Wilson R., Broemer M., Santoro M.M., Day C.L., RA Meier P.; RT "CARD-mediated autoinhibition of cIAP1's E3 ligase activity suppresses RT cell proliferation and migration."; RL Mol. Cell 42:569-583(2011). CC -!- FUNCTION: Multi-functional protein which regulates not only CC caspases and apoptosis, but also modulates inflammatory signaling CC and immunity, mitogenic kinase signaling, and cell proliferation, CC as well as cell invasion and metastasis. Acts as an E3 ubiquitin- CC protein ligase regulating NF-kappa-B signaling and regulates both CC canonical and non-canonical NF-kappa-B signaling by acting in CC opposite directions: acts as a positive regulator of the canonical CC pathway and suppresses constitutive activation of non-canonical CC NF-kappa-B signaling. The target proteins for its E3 ubiquitin- CC protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CC CASP3, CASP7, CASP8, TRAF2, DIABLO/SMAC, MAP3K14/NIK, MAP3K5/ASK1, CC IKBKG/NEMO, IKBKE and MXD1/MAD1. Can also function as an E3 CC ubiquitin-protein ligase of the NEDD8 conjugation pathway, CC targeting effector caspases for neddylation and inactivation. Acts CC as an important regulator of innate immune signaling via CC regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) CC and RIG-I like receptors (RLRs), collectively referred to as CC pattern recognition receptors (PRRs). Protects cells from CC spontaneous formation of the ripoptosome, a large multi-protein CC complex that has the capability to kill cancer cells in a caspase- CC dependent and caspase-independent manner. Suppresses ripoptosome CC formation by ubiquitinating RIPK1 and CASP8. Can stimulate the CC transcriptional activity of E2F1. Plays a role in the modulation CC of the cell cycle. {ECO:0000269|PubMed:15665297, CC ECO:0000269|PubMed:18082613, ECO:0000269|PubMed:21145488, CC ECO:0000269|PubMed:21653699, ECO:0000269|PubMed:21931591, CC ECO:0000269|PubMed:23453969}. CC -!- CATALYTIC ACTIVITY: S-ubiquitinyl-[E2 ubiquitin-conjugating CC enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin- CC conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor CC protein]-L-lysine. {ECO:0000269|PubMed:18082613, CC ECO:0000269|PubMed:21145488, ECO:0000269|PubMed:21931591, CC ECO:0000269|PubMed:23453969}. CC -!- ENZYME REGULATION: The CARD domain inhibits the activation of E3 CC ubiquitin ligase activity by preventing RING domain dimerization CC and E2 ubiquitin donor binding and activation. The CARD domain- CC mediated autoinhibition of the E3 ubiquitin-protein ligase CC activity suppresses cell proliferation and migration. USP19 CC regulates the stability of BIRC2/c-IAP1 by preventing its CC ubiquitination. {ECO:0000269|PubMed:21549626, CC ECO:0000269|PubMed:21849505}. CC -!- SUBUNIT: Interacts with DIABLO/SMAC and with PRSS25; these CC interactions inhibit apoptotic suppressor activity. Interacts with CC CASP9. Interacts (via BIR domains) with TRAF2; the interaction is CC required for IKBKE ubiquitination. Interacts with E2F1, RIPK1, CC RIPK2, RIPK3, RIPK4, BIRC5/survivin and USP19. Interacts with CC HSP90AB1 (PubMed:25486457). Interacts with UBXN1 CC (PubMed:25681446). {ECO:0000269|PubMed:15665297, CC ECO:0000269|PubMed:19153467, ECO:0000269|PubMed:21653699, CC ECO:0000269|PubMed:21849505, ECO:0000269|PubMed:21931591, CC ECO:0000269|PubMed:25486457, ECO:0000269|PubMed:25681446}. CC -!- INTERACTION: CC Q96CA5:BIRC7; NbExp=3; IntAct=EBI-514538, EBI-517623; CC Q3E793:BOL1 (xeno); NbExp=3; IntAct=EBI-514538, EBI-2344281; CC Q9Y3E2:BOLA1; NbExp=5; IntAct=EBI-514538, EBI-1049556; CC P55210:CASP7; NbExp=2; IntAct=EBI-514538, EBI-523958; CC P55211:CASP9; NbExp=9; IntAct=EBI-514538, EBI-516799; CC Q9NR28:DIABLO; NbExp=6; IntAct=EBI-514538, EBI-517508; CC Q96CJ1:EAF2; NbExp=3; IntAct=EBI-514538, EBI-1245604; CC Q9NQT4:EXOSC5; NbExp=5; IntAct=EBI-514538, EBI-371876; CC Q96CN9:GCC1; NbExp=5; IntAct=EBI-514538, EBI-746252; CC P32502:GCD7 (xeno); NbExp=3; IntAct=EBI-514538, EBI-6260; CC P14136:GFAP; NbExp=3; IntAct=EBI-514538, EBI-744302; CC P40325:HUA1 (xeno); NbExp=3; IntAct=EBI-514538, EBI-23614; CC P08949:NMB; NbExp=3; IntAct=EBI-514538, EBI-7964376; CC P08949-2:NMB; NbExp=5; IntAct=EBI-514538, EBI-12302085; CC Q96FW1:OTUB1; NbExp=3; IntAct=EBI-514538, EBI-1058491; CC Q8N3J5:PPM1K; NbExp=5; IntAct=EBI-514538, EBI-3923368; CC P63000:RAC1; NbExp=2; IntAct=EBI-514538, EBI-413628; CC P38339:RGD1 (xeno); NbExp=3; IntAct=EBI-514538, EBI-15065; CC Q13546:RIPK1; NbExp=3; IntAct=EBI-514538, EBI-358507; CC O43353:RIPK2; NbExp=3; IntAct=EBI-514538, EBI-358522; CC Q9Y572:RIPK3; NbExp=3; IntAct=EBI-514538, EBI-298250; CC P57078:RIPK4; NbExp=3; IntAct=EBI-514538, EBI-4422308; CC Q9NP84:TNFRSF12A; NbExp=2; IntAct=EBI-514538, EBI-2851995; CC Q12933:TRAF2; NbExp=12; IntAct=EBI-514538, EBI-355744; CC Q9BZW7:TSGA10; NbExp=4; IntAct=EBI-514538, EBI-744794; CC Q96HA8:WDYHV1; NbExp=3; IntAct=EBI-514538, EBI-741158; CC Q01976:YSA1 (xeno); NbExp=3; IntAct=EBI-514538, EBI-2344265; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Agents that induce CC either the extrinsic or intrinsic apoptotic pathways promote its CC redistribution from the nuclear compartment to the cytoplasmic CC compartment. Associated with the midbody in telophase cells, and CC found diffusely in the nucleus of interphase cells. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q13490-1; Sequence=Displayed; CC Name=2; CC IsoId=Q13490-2; Sequence=VSP_045314; CC -!- TISSUE SPECIFICITY: Present in many fetal and adult tissues. CC Mainly expressed in adult skeletal muscle, thymus, testis, ovary, CC and pancreas, low or absent in brain and peripheral blood CC leukocytes. CC -!- DOMAIN: The BIR domains mediate nuclear localization. CC {ECO:0000269|PubMed:21549626}. CC -!- DOMAIN: The CARD domain is necessary to stabilize the protein and CC inhibit the activation of E3 ubiquitin-protein ligase activity of CC BIRC2/c-IAP1 by preventing RING domain dimerization and E2 CC ubiquitin donor binding and activation. CC {ECO:0000269|PubMed:21549626}. CC -!- PTM: Auto-ubiquitinated and degraded by the proteasome in CC apoptotic cells. CC -!- SIMILARITY: Belongs to the IAP family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/birc2/"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/BIRC2ID795ch11q22.html"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; L49431; AAC41942.1; -; mRNA. DR EMBL; U45879; AAC50372.1; -; mRNA. DR EMBL; U37547; AAC50508.1; -; mRNA. DR EMBL; AK303197; BAG64288.1; -; mRNA. DR EMBL; AP000942; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; DQ068066; AAY46158.1; -; Genomic_DNA. DR EMBL; BC016174; AAH16174.1; -; mRNA. DR EMBL; BC028578; AAH28578.1; -; mRNA. DR CCDS; CCDS58169.1; -. [Q13490-2] DR CCDS; CCDS8316.1; -. [Q13490-1] DR PIR; S68450; S68450. DR RefSeq; NP_001157.1; NM_001166.4. [Q13490-1] DR RefSeq; NP_001243092.1; NM_001256163.1. [Q13490-1] DR RefSeq; NP_001243095.1; NM_001256166.1. [Q13490-2] DR UniGene; Hs.696238; -. DR UniGene; Hs.731943; -. DR PDB; 1QBH; NMR; -; A=266-363. DR PDB; 2L9M; NMR; -; A=435-562. DR PDB; 3D9T; X-ray; 1.50 A; A/B=260-352. DR PDB; 3D9U; X-ray; 2.30 A; A=260-352. DR PDB; 3M1D; X-ray; 2.00 A; A/B=40-119. DR PDB; 3MUP; X-ray; 2.60 A; A/B/C/D=251-363. DR PDB; 3OZ1; X-ray; 3.00 A; A/B/C/D=251-363. DR PDB; 3T6P; X-ray; 1.90 A; A=265-618. DR PDB; 3UW4; X-ray; 1.79 A; A=266-343. DR PDB; 4EB9; X-ray; 2.60 A; A/B/C/D=251-363. DR PDB; 4HY4; X-ray; 1.25 A; A/B=260-352. DR PDB; 4HY5; X-ray; 1.75 A; A/B=260-352. DR PDB; 4KMN; X-ray; 1.52 A; A=260-357. DR PDB; 4LGE; X-ray; 1.55 A; A/B=260-352. DR PDB; 4LGU; X-ray; 2.00 A; A/B=260-352. DR PDB; 4MTI; X-ray; 2.15 A; A/B=260-352. DR PDB; 4MU7; X-ray; 1.79 A; A/B=260-352. DR PDB; 5M6N; X-ray; 1.80 A; A/B=266-363. DR PDBsum; 1QBH; -. DR PDBsum; 2L9M; -. DR PDBsum; 3D9T; -. DR PDBsum; 3D9U; -. DR PDBsum; 3M1D; -. DR PDBsum; 3MUP; -. DR PDBsum; 3OZ1; -. DR PDBsum; 3T6P; -. DR PDBsum; 3UW4; -. DR PDBsum; 4EB9; -. DR PDBsum; 4HY4; -. DR PDBsum; 4HY5; -. DR PDBsum; 4KMN; -. DR PDBsum; 4LGE; -. DR PDBsum; 4LGU; -. DR PDBsum; 4MTI; -. DR PDBsum; 4MU7; -. DR PDBsum; 5M6N; -. DR ProteinModelPortal; Q13490; -. DR SMR; Q13490; -. DR BioGrid; 106826; 162. DR CORUM; Q13490; -. DR DIP; DIP-33485N; -. DR IntAct; Q13490; 80. DR MINT; Q13490; -. DR STRING; 9606.ENSP00000227758; -. DR BindingDB; Q13490; -. DR ChEMBL; CHEMBL5462; -. DR GuidetoPHARMACOLOGY; 2791; -. DR MEROPS; I32.007; -. DR CarbonylDB; Q13490; -. DR iPTMnet; Q13490; -. DR PhosphoSitePlus; Q13490; -. DR BioMuta; BIRC2; -. DR DMDM; 2497238; -. DR EPD; Q13490; -. DR MaxQB; Q13490; -. DR PaxDb; Q13490; -. DR PeptideAtlas; Q13490; -. DR PRIDE; Q13490; -. DR ProteomicsDB; 59484; -. DR DNASU; 329; -. DR Ensembl; ENST00000227758; ENSP00000227758; ENSG00000110330. [Q13490-1] DR Ensembl; ENST00000530675; ENSP00000431723; ENSG00000110330. [Q13490-2] DR Ensembl; ENST00000613397; ENSP00000477613; ENSG00000110330. [Q13490-1] DR GeneID; 329; -. DR KEGG; hsa:329; -. DR UCSC; uc001pgy.5; human. [Q13490-1] DR CTD; 329; -. DR DisGeNET; 329; -. DR EuPathDB; HostDB:ENSG00000110330.8; -. DR GeneCards; BIRC2; -. DR HGNC; HGNC:590; BIRC2. DR HPA; CAB020661; -. DR HPA; HPA005513; -. DR MIM; 601712; gene. DR neXtProt; NX_Q13490; -. DR OpenTargets; ENSG00000110330; -. DR PharmGKB; PA25359; -. DR eggNOG; KOG1101; Eukaryota. DR eggNOG; ENOG410YPNM; LUCA. DR GeneTree; ENSGT00500000044782; -. DR HOGENOM; HOG000232059; -. DR HOVERGEN; HBG004848; -. DR InParanoid; Q13490; -. DR KO; K16060; -. DR OMA; CSMVLAP; -. DR OrthoDB; EOG091G0CXH; -. DR PhylomeDB; Q13490; -. DR TreeFam; TF105356; -. DR Reactome; R-HSA-111465; Apoptotic cleavage of cellular proteins. DR Reactome; R-HSA-168638; NOD1/2 Signaling Pathway. DR Reactome; R-HSA-168927; TICAM1, RIP1-mediated IKK complex recruitment. DR Reactome; R-HSA-5213460; RIPK1-mediated regulated necrosis. DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling. DR Reactome; R-HSA-5357956; TNFR1-induced NFkappaB signaling pathway. DR Reactome; R-HSA-5668541; TNFR2 non-canonical NF-kB pathway. DR Reactome; R-HSA-5675482; Regulation of necroptotic cell death. DR Reactome; R-HSA-5676594; TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway. DR Reactome; R-HSA-5689880; Ub-specific processing proteases. DR Reactome; R-HSA-937041; IKK complex recruitment mediated by RIP1. DR SignaLink; Q13490; -. DR SIGNOR; Q13490; -. DR ChiTaRS; BIRC2; human. DR EvolutionaryTrace; Q13490; -. DR GeneWiki; BIRC2; -. DR GenomeRNAi; 329; -. DR PMAP-CutDB; Q13490; -. DR PRO; PR:Q13490; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; ENSG00000110330; -. DR CleanEx; HS_BIRC2; -. DR ExpressionAtlas; Q13490; baseline and differential. DR Genevisible; Q13490; HS. DR GO; GO:0035631; C:CD40 receptor complex; ISS:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISS:BHF-UCL. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0045121; C:membrane raft; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0001741; C:XY body; IEA:Ensembl. DR GO; GO:0051087; F:chaperone binding; IPI:UniProtKB. DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IBA:GO_Central. DR GO; GO:0098770; F:FBXO family protein binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0047485; F:protein N-terminus binding; IPI:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; IMP:UniProtKB. DR GO; GO:0016740; F:transferase activity; EXP:Reactome. DR GO; GO:0043130; F:ubiquitin binding; IDA:ParkinsonsUK-UCL. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc. DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; TAS:Reactome. DR GO; GO:1990001; P:inhibition of cysteine-type endopeptidase activity involved in apoptotic process; IBA:GO_Central. DR GO; GO:0070266; P:necroptotic process; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0060546; P:negative regulation of necroptotic process; IBA:GO_Central. DR GO; GO:1902443; P:negative regulation of ripoptosome assembly involved in necroptotic process; IEA:Ensembl. DR GO; GO:0038061; P:NIK/NF-kappaB signaling; TAS:UniProtKB. DR GO; GO:0001890; P:placenta development; IEA:Ensembl. DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEP:UniProtKB. DR GO; GO:1902524; P:positive regulation of protein K48-linked ubiquitination; IDA:UniProtKB. DR GO; GO:1902523; P:positive regulation of protein K63-linked ubiquitination; IDA:UniProtKB. DR GO; GO:1902527; P:positive regulation of protein monoubiquitination; IDA:UniProtKB. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProtKB. DR GO; GO:0016579; P:protein deubiquitination; TAS:Reactome. DR GO; GO:0051291; P:protein heterooligomerization; IEA:Ensembl. DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB. DR GO; GO:0042981; P:regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0051726; P:regulation of cell cycle; IDA:UniProtKB. DR GO; GO:0045595; P:regulation of cell differentiation; TAS:UniProtKB. DR GO; GO:0042127; P:regulation of cell proliferation; TAS:UniProtKB. DR GO; GO:2000116; P:regulation of cysteine-type endopeptidase activity; TAS:UniProtKB. DR GO; GO:0050727; P:regulation of inflammatory response; TAS:UniProtKB. DR GO; GO:0045088; P:regulation of innate immune response; TAS:UniProtKB. DR GO; GO:0060544; P:regulation of necroptotic process; IMP:UniProtKB. DR GO; GO:1901222; P:regulation of NIK/NF-kappaB signaling; IEA:Ensembl. DR GO; GO:0070424; P:regulation of nucleotide-binding oligomerization domain containing signaling pathway; TAS:UniProtKB. DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IEA:Ensembl. DR GO; GO:0039535; P:regulation of RIG-I signaling pathway; TAS:UniProtKB. DR GO; GO:0034121; P:regulation of toll-like receptor signaling pathway; TAS:UniProtKB. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; TAS:Reactome. DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl. DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; TAS:Reactome. DR CDD; cd00022; BIR; 3. DR InterPro; IPR001370; BIR_rpt. DR InterPro; IPR001315; CARD. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR001841; Znf_RING. DR Pfam; PF00653; BIR; 3. DR Pfam; PF00619; CARD; 1. DR SMART; SM00238; BIR; 3. DR SMART; SM00114; CARD; 1. DR SMART; SM00184; RING; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR PROSITE; PS01282; BIR_REPEAT_1; 3. DR PROSITE; PS50143; BIR_REPEAT_2; 3. DR PROSITE; PS50209; CARD; 1. DR PROSITE; PS50089; ZF_RING_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Apoptosis; KW Complete proteome; Cytoplasm; Metal-binding; Nucleus; Polymorphism; KW Reference proteome; Repeat; Transcription; Transcription regulation; KW Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc; KW Zinc-finger. FT CHAIN 1 618 Baculoviral IAP repeat-containing protein FT 2. FT /FTId=PRO_0000122347. FT REPEAT 46 113 BIR 1. FT REPEAT 184 250 BIR 2. FT REPEAT 269 336 BIR 3. FT DOMAIN 453 543 CARD. {ECO:0000255|PROSITE- FT ProRule:PRU00046}. FT ZN_FING 571 606 RING-type. {ECO:0000255|PROSITE- FT ProRule:PRU00175}. FT METAL 306 306 Zinc. FT METAL 309 309 Zinc. FT METAL 326 326 Zinc. FT METAL 333 333 Zinc. FT VAR_SEQ 1 49 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_045314. FT VARIANT 453 453 M -> I (in dbSNP:rs34749508). FT /FTId=VAR_049535. FT VARIANT 453 453 M -> V (in dbSNP:rs370745983). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_025016. FT VARIANT 506 506 A -> V (in dbSNP:rs34510872). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_025017. FT VARIANT 549 549 P -> S (in dbSNP:rs35494784). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_025018. FT CONFLICT 157 157 S -> P (in Ref. 2; AAC50372). FT {ECO:0000305}. FT CONFLICT 308 308 C -> G (in Ref. 2; AAC50372). FT {ECO:0000305}. FT CONFLICT 414 414 Q -> L (in Ref. 2; AAC50372). FT {ECO:0000305}. FT CONFLICT 514 514 L -> W (in Ref. 2; AAC50372). FT {ECO:0000305}. FT HELIX 43 51 {ECO:0000244|PDB:3M1D}. FT HELIX 52 55 {ECO:0000244|PDB:3M1D}. FT HELIX 64 69 {ECO:0000244|PDB:3M1D}. FT STRAND 72 74 {ECO:0000244|PDB:3M1D}. FT STRAND 81 83 {ECO:0000244|PDB:3M1D}. FT TURN 84 86 {ECO:0000244|PDB:3M1D}. FT HELIX 99 106 {ECO:0000244|PDB:3M1D}. FT HELIX 111 117 {ECO:0000244|PDB:3M1D}. FT HELIX 264 266 {ECO:0000244|PDB:4HY4}. FT HELIX 269 274 {ECO:0000244|PDB:4HY4}. FT TURN 275 278 {ECO:0000244|PDB:4HY4}. FT STRAND 279 282 {ECO:0000244|PDB:1QBH}. FT STRAND 283 285 {ECO:0000244|PDB:4HY4}. FT HELIX 287 292 {ECO:0000244|PDB:4HY4}. FT STRAND 295 297 {ECO:0000244|PDB:4HY4}. FT STRAND 304 306 {ECO:0000244|PDB:4HY4}. FT TURN 307 309 {ECO:0000244|PDB:4HY4}. FT STRAND 312 314 {ECO:0000244|PDB:3D9T}. FT HELIX 322 329 {ECO:0000244|PDB:4HY4}. FT HELIX 334 340 {ECO:0000244|PDB:4HY4}. FT HELIX 342 348 {ECO:0000244|PDB:4HY4}. FT HELIX 355 361 {ECO:0000244|PDB:5M6N}. FT HELIX 389 391 {ECO:0000244|PDB:3T6P}. FT HELIX 394 401 {ECO:0000244|PDB:3T6P}. FT HELIX 406 420 {ECO:0000244|PDB:3T6P}. FT HELIX 427 450 {ECO:0000244|PDB:3T6P}. FT TURN 451 453 {ECO:0000244|PDB:2L9M}. FT HELIX 456 463 {ECO:0000244|PDB:3T6P}. FT HELIX 465 471 {ECO:0000244|PDB:3T6P}. FT HELIX 476 484 {ECO:0000244|PDB:3T6P}. FT STRAND 485 487 {ECO:0000244|PDB:2L9M}. FT HELIX 490 497 {ECO:0000244|PDB:3T6P}. FT HELIX 502 516 {ECO:0000244|PDB:3T6P}. FT HELIX 518 531 {ECO:0000244|PDB:3T6P}. FT HELIX 533 540 {ECO:0000244|PDB:3T6P}. FT HELIX 553 555 {ECO:0000244|PDB:3T6P}. FT HELIX 558 566 {ECO:0000244|PDB:3T6P}. FT TURN 572 574 {ECO:0000244|PDB:3T6P}. FT STRAND 575 578 {ECO:0000244|PDB:3T6P}. FT STRAND 581 584 {ECO:0000244|PDB:3T6P}. FT STRAND 589 591 {ECO:0000244|PDB:3T6P}. FT TURN 593 595 {ECO:0000244|PDB:3T6P}. FT HELIX 596 598 {ECO:0000244|PDB:3T6P}. FT TURN 603 605 {ECO:0000244|PDB:3T6P}. FT STRAND 611 614 {ECO:0000244|PDB:3T6P}. SQ SEQUENCE 618 AA; 69900 MW; C1778D328063586D CRC64; MHKTASQRLF PGPSYQNIKS IMEDSTILSD WTNSNKQKMK YDFSCELYRM STYSTFPAGV PVSERSLARA GFYYTGVNDK VKCFCCGLML DNWKLGDSPI QKHKQLYPSC SFIQNLVSAS LGSTSKNTSP MRNSFAHSLS PTLEHSSLFS GSYSSLSPNP LNSRAVEDIS SSRTNPYSYA MSTEEARFLT YHMWPLTFLS PSELARAGFY YIGPGDRVAC FACGGKLSNW EPKDDAMSEH RRHFPNCPFL ENSLETLRFS ISNLSMQTHA ARMRTFMYWP SSVPVQPEQL ASAGFYYVGR NDDVKCFCCD GGLRCWESGD DPWVEHAKWF PRCEFLIRMK GQEFVDEIQG RYPHLLEQLL STSDTTGEEN ADPPIIHFGP GESSSEDAVM MNTPVVKSAL EMGFNRDLVK QTVQSKILTT GENYKTVNDI VSALLNAEDE KREEEKEKQA EEMASDDLSL IRKNRMALFQ QLTCVLPILD NLLKANVINK QEHDIIKQKT QIPLQARELI DTILVKGNAA ANIFKNCLKE IDSTLYKNLF VDKNMKYIPT EDVSGLSLEE QLRRLQEERT CKVCMDKEVS VVFIPCGHLV VCQECAPSLR KCPICRGIIK GTVRTFLS // ID CAR11_HUMAN Reviewed; 1154 AA. AC Q9BXL7; A4D1Z7; Q2NKN7; Q548H3; DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot. DT 26-FEB-2008, sequence version 3. DT 18-JUL-2018, entry version 160. DE RecName: Full=Caspase recruitment domain-containing protein 11; DE AltName: Full=CARD-containing MAGUK protein 1; DE Short=Carma 1; GN Name=CARD11; Synonyms=CARMA1 {ECO:0000303|PubMed:11356195}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH BCL10, AND RP TISSUE SPECIFICITY. RX PubMed=11278692; DOI=10.1074/jbc.M010512200; RA Bertin J., Wang L., Guo Y., Jacobson M.D., Poyet J.-L., RA Srinivasula S.M., Merriam S., DiStefano P.S., Alnemri E.S.; RT "CARD11 and CARD14 are novel caspase recruitment domain RT (CARD)/membrane-associated guanylate kinase (MAGUK) family members RT that interact with Bcl10 and activate NF-kappaB."; RL J. Biol. Chem. 276:11877-11882(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., RA Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., RA Mural R.J., Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-1154, FUNCTION, AND INTERACTION WITH RP BCL10. RX PubMed=11356195; DOI=10.1016/S0014-5793(01)02414-0; RA Gaide O., Martinon F., Micheau O., Bonnet D., Thome M., Tschopp J.; RT "Carma1, a CARD-containing binding partner of Bcl10, induces Bcl10 RT phosphorylation and NF-kappaB activation."; RL FEBS Lett. 496:121-127(2001). RN [6] RP ERRATUM. RA Gaide O., Martinon F., Micheau O., Bonnet D., Thome M., Tschopp J.; RL FEBS Lett. 505:198-198(2001). RN [7] RP FUNCTION. RX PubMed=12356734; DOI=10.1093/emboj/cdf505; RA Pomerantz J.L., Denny E.M., Baltimore D.; RT "CARD11 mediates factor-specific activation of NF-kappaB by the T cell RT receptor complex."; RL EMBO J. 21:5184-5194(2002). RN [8] RP IDENTIFICATION IN A MEMBRANE RAFT COMPLEX, INTERACTION WITH DPP4, RP SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=17287217; DOI=10.1074/jbc.M609157200; RA Ohnuma K., Uchiyama M., Yamochi T., Nishibashi K., Hosono O., RA Takahashi N., Kina S., Tanaka H., Lin X., Dang N.H., Morimoto C.; RT "Caveolin-1 triggers T-cell activation via CD26 in association with RT CARMA1."; RL J. Biol. Chem. 282:10117-10131(2007). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-466; SER-593 AND RP SER-925, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP INVOLVEMENT IN IMD11A. RX PubMed=23374270; DOI=10.1016/j.jaci.2012.11.050; RA Stepensky P., Keller B., Buchta M., Kienzler A.K., Elpeleg O., RA Somech R., Cohen S., Shachar I., Miosge L.A., Schlesier M., Fuchs I., RA Enders A., Eibel H., Grimbacher B., Warnatz K.; RT "Deficiency of caspase recruitment domain family, member 11 (CARD11), RT causes profound combined immunodeficiency in human subjects."; RL J. Allergy Clin. Immunol. 131:477-485(2013). RN [12] RP INVOLVEMENT IN BENTA, VARIANTS BENTA SER-123 AND GLY-134, AND RP CHARACTERIZATION OF VARIANTS BENTA SER-123 AND GLY-134. RX PubMed=23129749; DOI=10.1084/jem.20120831; RA Snow A.L., Xiao W., Stinson J.R., Lu W., Chaigne-Delalande B., RA Zheng L., Pittaluga S., Matthews H.F., Schmitz R., Jhavar S., RA Kuchen S., Kardava L., Wang W., Lamborn I.T., Jing H., Raffeld M., RA Moir S., Fleisher T.A., Staudt L.M., Su H.C., Lenardo M.J.; RT "Congenital B cell lymphocytosis explained by novel germline CARD11 RT mutations."; RL J. Exp. Med. 209:2247-2261(2012). RN [13] RP INVOLVEMENT IN IMD11A, VARIANT IMD11A 945-GLN--LEU-1154 DEL, AND RP CHARACTERIZATION OF VARIANT IMD11A 945-GLN--LEU-1154 DEL. RX PubMed=23561803; DOI=10.1016/j.jaci.2013.02.012; RA Greil J., Rausch T., Giese T., Bandapalli O.R., Daniel V., RA Bekeredjian-Ding I., Stuetz A.M., Drees C., Roth S., Ruland J., RA Korbel J.O., Kulozik A.E.; RT "Whole-exome sequencing links caspase recruitment domain 11 (CARD11) RT inactivation to severe combined immunodeficiency."; RL J. Allergy Clin. Immunol. 131:1376-1383(2013). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-448; SER-512; SER-535; RP SER-593; SER-886 AND SER-925, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [15] RP INVOLVEMENT IN IMD11B, VARIANTS IMD11B ASP-57; PRO-194 AND TRP-975, RP CHARACTERIZATION OF VARIANTS IMD11B ASP-57; PRO-194 AND TRP-975, RP CHARACTERIZATION OF VARIANT BENTA GLY-134, FUNCTION, AND INTERACTION RP WITH BCL10. RX PubMed=28628108; DOI=10.1038/ng.3898; RA Ma C.A., Stinson J.R., Zhang Y., Abbott J.K., Weinreich M.A., RA Hauk P.J., Reynolds P.R., Lyons J.J., Nelson C.G., Ruffo E., RA Dorjbal B., Glauzy S., Yamakawa N., Arjunaraja S., Voss K., RA Stoddard J., Niemela J., Zhang Y., Rosenzweig S.D., McElwee J.J., RA DiMaggio T., Matthews H.F., Jones N., Stone K.D., Palma A., RA Oleastro M., Prieto E., Bernasconi A.R., Dubra G., Danielian S., RA Zaiat J., Marti M.A., Kim B., Cooper M.A., Romberg N., Meffre E., RA Gelfand E.W., Snow A.L., Milner J.D.; RT "Germline hypomorphic CARD11 mutations in severe atopic disease."; RL Nat. Genet. 49:1192-1201(2017). CC -!- FUNCTION: Involved in the costimulatory signal essential for T- CC cell receptor (TCR)-mediated T-cell activation. Its binding to CC DPP4 induces T-cell proliferation and NF-kappa-B activation in a CC T-cell receptor/CD3-dependent manner. Activates NF-kappa-B via CC BCL10 and IKK. Stimulates the phosphorylation of BCL10. Also CC activates the TORC1 signaling pathway. CC {ECO:0000269|PubMed:11278692, ECO:0000269|PubMed:11356195, CC ECO:0000269|PubMed:12356734, ECO:0000269|PubMed:28628108}. CC -!- SUBUNIT: Found in a membrane raft complex, at least composed of CC BCL10, CARD11, DPP4 and IKBKB. CARD11 and BCL10 bind to each other CC by CARD-CARD interaction. Interacts (via PDZ domain) with DPP4 CC (via cytoplasmic tail). Interacts with BCL10; as part of a CBM CC (CARD11-BCL10-MALT1) complex involved in NF-kappa-B activation CC (PubMed:28628108). {ECO:0000269|PubMed:11278692, CC ECO:0000269|PubMed:11356195, ECO:0000269|PubMed:17287217, CC ECO:0000269|PubMed:28628108}. CC -!- INTERACTION: CC O95999:BCL10; NbExp=7; IntAct=EBI-7006141, EBI-958922; CC Q13191-1:CBLB; NbExp=4; IntAct=EBI-7006141, EBI-15555129; CC P48729:CSNK1A1; NbExp=5; IntAct=EBI-7006141, EBI-1383726; CC P48729-1:CSNK1A1; NbExp=5; IntAct=EBI-7006141, EBI-10106282; CC Q9UDY8:MALT1; NbExp=2; IntAct=EBI-7006141, EBI-1047372; CC P70218:Map4k1 (xeno); NbExp=2; IntAct=EBI-7006141, EBI-2906801; CC Q05655:PRKCD; NbExp=7; IntAct=EBI-7006141, EBI-704279; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17287217}. CC Membrane raft {ECO:0000269|PubMed:17287217}. Note=Colocalized with CC DPP4 in membrane rafts. {ECO:0000269|PubMed:17287217}. CC -!- TISSUE SPECIFICITY: Detected in adult peripheral blood leukocytes, CC thymus, spleen and liver. Also found in promyelocytic leukemia HL- CC 60 cells, chronic myelogenous leukemia K-562 cells, Burkitt's CC lymphoma Raji cells and colorectal adenocarcinoma SW480 cells. Not CC detected in HeLaS3, MOLT-4, A-549 and G431 cells. CC {ECO:0000269|PubMed:11278692}. CC -!- PTM: Phosphorylation at Ser-559, Ser-644 and Ser-652 by PRKCB and CC PRKCQ leads to a shift from an inactive to an active form that CC activates the NF-kappa-B signaling. CC {ECO:0000250|UniProtKB:Q8CIS0}. CC -!- DISEASE: B-cell expansion with NFKB and T-cell anergy (BENTA) CC [MIM:616452]: An autosomal dominant condition characterized by CC onset in infancy of splenomegaly and polyclonal expansion of B CC cells, resulting in peripheral lymphocytosis. Affected individuals CC also show mild immune dysfunction, including some defective CC antibody responses and T-cell anergy. There may be a CC predisposition to the development of B-cell malignancy. CC {ECO:0000269|PubMed:23129749, ECO:0000269|PubMed:28628108}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- DISEASE: Immunodeficiency 11 A (IMD11A) [MIM:615206]: An autosomal CC recessive primary immunodeficiency characterized by normal numbers CC of T and B-lymphocytes, but defective intracellular signaling. CC There is a block in B-cell differentiation with increased numbers CC of transitional B-cells and hypogammaglobulinemia, as well as CC decreased numbers of regulatory T-cells and defects in T-cell CC function. {ECO:0000269|PubMed:23374270, CC ECO:0000269|PubMed:23561803}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Immunodeficiency 11B with atopic dermatitis (IMD11B) CC [MIM:617638]: An autosomal dominant disorder of immune dysfunction CC characterized by onset of moderate to severe atopic dermatitis in CC early childhood. Some patients may have recurrent infections and CC other variable immune abnormalities. Laboratory studies show CC defects in T-cell activation, increased IgE, and eosinophilia. CC {ECO:0000269|PubMed:28628108}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- CAUTION: Supposed to contain a SH3 domain which is not detected by CC PROSITE, Pfam or SMART. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAG53402.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAI11720.2; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAQ96893.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=EAL23962.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AF322641; AAG53402.1; ALT_INIT; mRNA. DR EMBL; AC004906; AAQ96893.1; ALT_SEQ; Genomic_DNA. DR EMBL; CH236953; EAL23962.1; ALT_SEQ; Genomic_DNA. DR EMBL; BC111719; AAI11720.2; ALT_INIT; mRNA. DR EMBL; AF352576; AAL34460.1; -; mRNA. DR CCDS; CCDS5336.2; -. DR RefSeq; NP_001311210.1; NM_001324281.1. DR RefSeq; NP_115791.3; NM_032415.5. DR RefSeq; XP_011513888.1; XM_011515586.2. DR UniGene; Hs.648101; -. DR PDB; 4JUP; X-ray; 3.20 A; A/B=21-116. DR PDB; 4LWD; X-ray; 1.79 A; A=18-110. DR PDBsum; 4JUP; -. DR PDBsum; 4LWD; -. DR ProteinModelPortal; Q9BXL7; -. DR SMR; Q9BXL7; -. DR BioGrid; 124073; 30. DR CORUM; Q9BXL7; -. DR DIP; DIP-41797N; -. DR IntAct; Q9BXL7; 16. DR MINT; Q9BXL7; -. DR STRING; 9606.ENSP00000380150; -. DR iPTMnet; Q9BXL7; -. DR PhosphoSitePlus; Q9BXL7; -. DR BioMuta; CARD11; -. DR DMDM; 172046231; -. DR EPD; Q9BXL7; -. DR MaxQB; Q9BXL7; -. DR PaxDb; Q9BXL7; -. DR PeptideAtlas; Q9BXL7; -. DR PRIDE; Q9BXL7; -. DR ProteomicsDB; 79450; -. DR Ensembl; ENST00000396946; ENSP00000380150; ENSG00000198286. DR GeneID; 84433; -. DR KEGG; hsa:84433; -. DR UCSC; uc003smv.5; human. DR CTD; 84433; -. DR DisGeNET; 84433; -. DR EuPathDB; HostDB:ENSG00000198286.9; -. DR GeneCards; CARD11; -. DR H-InvDB; HIX0033921; -. DR HGNC; HGNC:16393; CARD11. DR HPA; HPA052984; -. DR MalaCards; CARD11; -. DR MIM; 607210; gene. DR MIM; 615206; phenotype. DR MIM; 616452; phenotype. DR MIM; 617638; phenotype. DR neXtProt; NX_Q9BXL7; -. DR OpenTargets; ENSG00000198286; -. DR Orphanet; 300324; Persistent polyclonal B-cell lymphocytosis. DR Orphanet; 357237; Severe combined immunodeficiency due to CARD11 deficiency. DR PharmGKB; PA26073; -. DR eggNOG; ENOG410ISRJ; Eukaryota. DR eggNOG; ENOG41126VR; LUCA. DR GeneTree; ENSGT00530000063108; -. DR HOVERGEN; HBG099790; -. DR InParanoid; Q9BXL7; -. DR KO; K07367; -. DR OMA; EACIVNL; -. DR OrthoDB; EOG091G0T58; -. DR PhylomeDB; Q9BXL7; -. DR TreeFam; TF351139; -. DR Reactome; R-HSA-1169091; Activation of NF-kappaB in B cells. DR Reactome; R-HSA-202424; Downstream TCR signaling. DR Reactome; R-HSA-2871837; FCERI mediated NF-kB activation. DR Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling. DR SignaLink; Q9BXL7; -. DR SIGNOR; Q9BXL7; -. DR ChiTaRS; CARD11; human. DR GeneWiki; CARD11; -. DR GenomeRNAi; 84433; -. DR PRO; PR:Q9BXL7; -. DR Proteomes; UP000005640; Chromosome 7. DR Bgee; ENSG00000198286; -. DR CleanEx; HS_CARD11; -. DR ExpressionAtlas; Q9BXL7; baseline and differential. DR Genevisible; Q9BXL7; HS. DR GO; GO:0032449; C:CBM complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0001772; C:immunological synapse; IEA:Ensembl. DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0050700; F:CARD domain binding; IPI:UniProtKB. DR GO; GO:0004385; F:guanylate kinase activity; NAS:UniProtKB. DR GO; GO:0030183; P:B cell differentiation; IEA:Ensembl. DR GO; GO:0042100; P:B cell proliferation; IEA:Ensembl. DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome. DR GO; GO:0048872; P:homeostasis of number of cells; IEA:Ensembl. DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB. DR GO; GO:0002377; P:immunoglobulin production; IEA:Ensembl. DR GO; GO:0070970; P:interleukin-2 secretion; IEA:Ensembl. DR GO; GO:0030890; P:positive regulation of B cell proliferation; IEA:Ensembl. DR GO; GO:0001819; P:positive regulation of cytokine production; IMP:UniProtKB. DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl. DR GO; GO:0045086; P:positive regulation of interleukin-2 biosynthetic process; IEA:Ensembl. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB. DR GO; GO:0042102; P:positive regulation of T cell proliferation; IEA:Ensembl. DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro. DR GO; GO:0045577; P:regulation of B cell differentiation; IEA:Ensembl. DR GO; GO:0045580; P:regulation of T cell differentiation; IEA:Ensembl. DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; TAS:Reactome. DR GO; GO:0031295; P:T cell costimulation; IDA:UniProtKB. DR GO; GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome. DR GO; GO:0045061; P:thymic T cell selection; IEA:Ensembl. DR GO; GO:0038202; P:TORC1 signaling; IMP:UniProtKB. DR InterPro; IPR001315; CARD. DR InterPro; IPR033538; CARD11. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR036034; PDZ_sf. DR PANTHER; PTHR14559:SF4; PTHR14559:SF4; 1. DR Pfam; PF00619; CARD; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR SUPFAM; SSF50156; SSF50156; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR PROSITE; PS50209; CARD; 1. PE 1: Evidence at protein level; KW 3D-structure; Coiled coil; Complete proteome; Cytoplasm; KW Disease mutation; Membrane; Phosphoprotein; Polymorphism; KW Reference proteome. FT CHAIN 1 1154 Caspase recruitment domain-containing FT protein 11. FT /FTId=PRO_0000144086. FT DOMAIN 18 110 CARD. {ECO:0000255|PROSITE- FT ProRule:PRU00046}. FT DOMAIN 667 755 PDZ. FT DOMAIN 973 1140 Guanylate kinase-like. FT COILED 130 449 {ECO:0000255}. FT MOD_RES 448 448 Phosphoserine. FT {ECO:0000244|PubMed:23186163}. FT MOD_RES 466 466 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 512 512 Phosphoserine. FT {ECO:0000244|PubMed:23186163}. FT MOD_RES 535 535 Phosphoserine. FT {ECO:0000244|PubMed:23186163}. FT MOD_RES 559 559 Phosphoserine; by PKC/PRKCB and FT PKC/PRKCQ. FT {ECO:0000250|UniProtKB:Q8CIS0}. FT MOD_RES 593 593 Phosphoserine. FT {ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:23186163}. FT MOD_RES 644 644 Phosphoserine; by PKC/PRKCB and FT PKC/PRKCQ. FT {ECO:0000250|UniProtKB:Q8CIS0}. FT MOD_RES 652 652 Phosphoserine; by PKC/PRKCB and FT PKC/PRKCQ. FT {ECO:0000250|UniProtKB:Q8CIS0}. FT MOD_RES 886 886 Phosphoserine. FT {ECO:0000244|PubMed:23186163}. FT MOD_RES 925 925 Phosphoserine. FT {ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:23186163}. FT VARIANT 57 57 E -> D (in IMD11B; no effect on protein FT abundance; decreased interaction with FT BCL10; dominant negative effect on NF- FT kappaB signaling; dominant negative FT effect on TORC1 signaling). FT {ECO:0000269|PubMed:28628108}. FT /FTId=VAR_079284. FT VARIANT 123 123 G -> S (in BENTA; results in protein FT aggregation; constitutive activation of FT NF-kappaB signaling; dbSNP:rs387907352). FT {ECO:0000269|PubMed:23129749}. FT /FTId=VAR_069710. FT VARIANT 134 134 E -> G (in BENTA; results in protein FT aggregation; constitutive activation of FT NF-kappaB signaling; dbSNP:rs387907351). FT {ECO:0000269|PubMed:23129749, FT ECO:0000269|PubMed:28628108}. FT /FTId=VAR_069711. FT VARIANT 194 194 L -> P (in IMD11B; no effect on protein FT abundance; decreased interaction with FT BCL10; dominant negative effect on NF- FT kappaB signaling; dominant negative FT effect on TORC1 signaling). FT {ECO:0000269|PubMed:28628108}. FT /FTId=VAR_079285. FT VARIANT 670 670 T -> M (in dbSNP:rs3735134). FT /FTId=VAR_028117. FT VARIANT 694 694 S -> L (in dbSNP:rs3735133). FT /FTId=VAR_028118. FT VARIANT 945 1154 Missing (in IMD11A; results in defective FT NF-kappa-B activation). FT {ECO:0000269|PubMed:23561803}. FT /FTId=VAR_079158. FT VARIANT 975 975 R -> W (in IMD11B; no effect on protein FT abundance; dominant negative effect on FT NF-kappaB signaling; dominant negative FT effect on TORC1 signaling; FT dbSNP:rs1064795307). FT {ECO:0000269|PubMed:28628108}. FT /FTId=VAR_079286. FT CONFLICT 815 815 L -> P (in Ref. 1; AAG53402). FT {ECO:0000305}. FT HELIX 24 27 {ECO:0000244|PDB:4LWD}. FT HELIX 30 36 {ECO:0000244|PDB:4LWD}. FT HELIX 39 48 {ECO:0000244|PDB:4LWD}. FT HELIX 54 61 {ECO:0000244|PDB:4LWD}. FT TURN 70 73 {ECO:0000244|PDB:4LWD}. FT HELIX 74 80 {ECO:0000244|PDB:4LWD}. FT HELIX 84 98 {ECO:0000244|PDB:4LWD}. FT HELIX 100 107 {ECO:0000244|PDB:4LWD}. SQ SEQUENCE 1154 AA; 133284 MW; 2F3512D903795D18 CRC64; MPGGGPEMDD YMETLKDEED ALWENVECNR HMLSRYINPA KLTPYLRQCK VIDEQDEDEV LNAPMLPSKI NRAGRLLDIL HTKGQRGYVV FLESLEFYYP ELYKLVTGKE PTRRFSTIVV EEGHEGLTHF LMNEVIKLQQ QMKAKDLQRC ELLARLRQLE DEKKQMTLTR VELLTFQERY YKMKEERDSY NDELVKVKDD NYNLAMRYAQ LSEEKNMAVM RSRDLQLEID QLKHRLNKME EECKLERNQS LKLKNDIENR PKKEQVLELE RENEMLKTKN QELQSIIQAG KRSLPDSDKA ILDILEHDRK EALEDRQELV NRIYNLQEEA RQAEELRDKY LEEKEDLELK CSTLGKDCEM YKHRMNTVML QLEEVERERD QAFHSRDEAQ TQYSQCLIEK DKYRKQIREL EEKNDEMRIE MVRREACIVN LESKLRRLSK DSNNLDQSLP RNLPVTIISQ DFGDASPRTN GQEADDSSTS EESPEDSKYF LPYHPPQRRM NLKGIQLQRA KSPISLKRTS DFQAKGHEEE GTDASPSSCG SLPITNSFTK MQPPRSRSSI MSITAEPPGN DSIVRRYKED APHRSTVEED NDSGGFDALD LDDDSHERYS FGPSSIHSSS SSHQSEGLDA YDLEQVNLMF RKFSLERPFR PSVTSVGHVR GPGPSVQHTT LNGDSLTSQL TLLGGNARGS FVHSVKPGSL AEKAGLREGH QLLLLEGCIR GERQSVPLDT CTKEEAHWTI QRCSGPVTLH YKVNHEGYRK LVKDMEDGLI TSGDSFYIRL NLNISSQLDA CTMSLKCDDV VHVRDTMYQD RHEWLCARVD PFTDHDLDMG TIPSYSRAQQ LLLVKLQRLM HRGSREEVDG THHTLRALRN TLQPEEALST SDPRVSPRLS RASFLFGQLL QFVSRSENKY KRMNSNERVR IISGSPLGSL ARSSLDATKL LTEKQEELDP ESELGKNLSL IPYSLVRAFY CERRRPVLFT PTVLAKTLVQ RLLNSGGAME FTICKSDIVT RDEFLRRQKT ETIIYSREKN PNAFECIAPA NIEAVAAKNK HCLLEAGIGC TRDLIKSNIY PIVLFIRVCE KNIKRFRKLL PRPETEEEFL RVCRLKEKEL EALPCLYATV EPDMWGSVEE LLRVVKDKIG EEQRKTIWVD EDQL // ID CAR11_MOUSE Reviewed; 1159 AA. AC Q8CIS0; Q4VA14; Q6KAS3; Q8BYV0; DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 26-FEB-2008, sequence version 2. DT 23-MAY-2018, entry version 124. DE RecName: Full=Caspase recruitment domain-containing protein 11; GN Name=Card11; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION. RC TISSUE=Thymus; RX PubMed=12356734; DOI=10.1093/emboj/cdf505; RA Pomerantz J.L., Denny E.M., Baltimore D.; RT "CARD11 mediates factor-specific activation of NF-kappaB by the T cell RT receptor complex."; RL EMBO J. 21:5184-5194(2002). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Thymus; RX PubMed=15449545; DOI=10.1093/dnares/11.2.127; RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., RA Saga Y., Kitamura H., Nakagawa T., Nagase T., Ohara O., Koga H.; RT "Prediction of the coding sequences of mouse homologues of FLJ genes: RT the complete nucleotide sequences of 110 mouse FLJ-homologous cDNAs RT identified by screening of terminal sequences of cDNA clones randomly RT sampled from size-fractionated libraries."; RL DNA Res. 11:127-135(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC STRAIN=129; TISSUE=Mammary tumor; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 611-1159. RC STRAIN=C57BL/6J; TISSUE=Thymus; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [5] RP FUNCTION, AND PHOSPHORYLATION AT SER-564; SER-649 AND SER-657. RX PubMed=16356855; DOI=10.1016/j.immuni.2005.09.014; RA Sommer K., Guo B., Pomerantz J.L., Bandaranayake A.D., RA Moreno-Garcia M.E., Ovechkina Y.L., Rawlings D.J.; RT "Phosphorylation of the CARMA1 linker controls NF-kappaB activation."; RL Immunity 23:561-574(2005). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-466; SER-512 AND RP SER-891, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Lung, and Spleen; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and RT expression."; RL Cell 143:1174-1189(2010). CC -!- FUNCTION: Involved in the costimulatory signal essential for T- CC cell receptor (TCR)-mediated T-cell activation (PubMed:12356734, CC PubMed:16356855). Its binding to DPP4 induces T-cell proliferation CC and NF-kappa-B activation in a T-cell receptor/CD3-dependent CC manner. Activates NF-kappa-B via BCL10 and IKK. Stimulates the CC phosphorylation of BCL10. Also activates the TORC1 signaling CC pathway (By similarity). {ECO:0000250|UniProtKB:Q9BXL7, CC ECO:0000269|PubMed:12356734, ECO:0000269|PubMed:16356855}. CC -!- SUBUNIT: Found in a membrane raft complex, at least composed of CC BCL10, CARD11, DPP4 and IKBKB. CARD11 and BCL10 bind to each other CC by CARD-CARD interaction. Interacts (via PDZ domain) with DPP4 CC (via cytoplasmic tail). Interacts with BCL10; as part of a CBM CC (CARD11-BCL10-MALT1) complex involved in NF-kappa-B activation. CC {ECO:0000250|UniProtKB:Q9BXL7}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9BXL7}. CC Membrane raft {ECO:0000250|UniProtKB:Q9BXL7}. Note=Colocalized CC with DPP4 in membrane rafts. {ECO:0000250|UniProtKB:Q9BXL7}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q8CIS0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8CIS0-2; Sequence=VSP_031595; CC -!- PTM: Phosphorylation at Ser-564, Ser-649 and Ser-657 by PRKCB and CC PRKCQ leads to a shift from an inactive to an active form that CC activates the NF-kappa-B signaling. {ECO:0000269|PubMed:16356855}. CC -!- CAUTION: Supposed to contain a SH3 domain which is not detected by CC PROSITE, Pfam or SMART. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAD21384.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AY135367; AAN10150.1; -; mRNA. DR EMBL; AK131134; BAD21384.1; ALT_INIT; mRNA. DR EMBL; BC096592; AAH96592.1; -; mRNA. DR EMBL; AK037968; BAC29910.1; -; mRNA. DR CCDS; CCDS51686.1; -. [Q8CIS0-2] DR RefSeq; NP_780571.2; NM_175362.2. [Q8CIS0-2] DR UniGene; Mm.46187; -. DR PDB; 4I16; X-ray; 1.75 A; A=18-110. DR PDBsum; 4I16; -. DR ProteinModelPortal; Q8CIS0; -. DR SMR; Q8CIS0; -. DR BioGrid; 224389; 3. DR DIP; DIP-49692N; -. DR IntAct; Q8CIS0; 7. DR MINT; Q8CIS0; -. DR STRING; 10090.ENSMUSP00000082941; -. DR iPTMnet; Q8CIS0; -. DR PhosphoSitePlus; Q8CIS0; -. DR SwissPalm; Q8CIS0; -. DR PaxDb; Q8CIS0; -. DR PeptideAtlas; Q8CIS0; -. DR PRIDE; Q8CIS0; -. DR Ensembl; ENSMUST00000085786; ENSMUSP00000082941; ENSMUSG00000036526. [Q8CIS0-2] DR GeneID; 108723; -. DR KEGG; mmu:108723; -. DR UCSC; uc009aik.2; mouse. [Q8CIS0-2] DR UCSC; uc012egd.1; mouse. [Q8CIS0-1] DR CTD; 84433; -. DR MGI; MGI:1916978; Card11. DR eggNOG; ENOG410ISRJ; Eukaryota. DR eggNOG; ENOG41126VR; LUCA. DR GeneTree; ENSGT00530000063108; -. DR HOGENOM; HOG000111299; -. DR HOVERGEN; HBG099790; -. DR InParanoid; Q8CIS0; -. DR KO; K07367; -. DR OMA; EACIVNL; -. DR OrthoDB; EOG091G0T58; -. DR PhylomeDB; Q8CIS0; -. DR TreeFam; TF351139; -. DR Reactome; R-MMU-1169091; Activation of NF-kappaB in B cells. DR Reactome; R-MMU-202424; Downstream TCR signaling. DR Reactome; R-MMU-2871837; FCERI mediated NF-kB activation. DR ChiTaRS; Card11; mouse. DR PRO; PR:Q8CIS0; -. DR Proteomes; UP000000589; Chromosome 5. DR Bgee; ENSMUSG00000036526; -. DR CleanEx; MM_CARD11; -. DR Genevisible; Q8CIS0; MM. DR GO; GO:0032449; C:CBM complex; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; ISO:MGI. DR GO; GO:0001772; C:immunological synapse; IDA:MGI. DR GO; GO:0045121; C:membrane raft; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0042101; C:T cell receptor complex; IEA:Ensembl. DR GO; GO:0050700; F:CARD domain binding; ISO:MGI. DR GO; GO:0030183; P:B cell differentiation; IMP:MGI. DR GO; GO:0042100; P:B cell proliferation; IMP:MGI. DR GO; GO:0048872; P:homeostasis of number of cells; IMP:MGI. DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB. DR GO; GO:0002377; P:immunoglobulin production; IMP:MGI. DR GO; GO:0070970; P:interleukin-2 secretion; IMP:MGI. DR GO; GO:0046649; P:lymphocyte activation; IMP:MGI. DR GO; GO:0030890; P:positive regulation of B cell proliferation; IMP:MGI. DR GO; GO:0001819; P:positive regulation of cytokine production; ISO:MGI. DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:MGI. DR GO; GO:0045086; P:positive regulation of interleukin-2 biosynthetic process; IMP:MGI. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:MGI. DR GO; GO:0050870; P:positive regulation of T cell activation; IMP:MGI. DR GO; GO:0042102; P:positive regulation of T cell proliferation; IMP:MGI. DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro. DR GO; GO:0045577; P:regulation of B cell differentiation; IMP:MGI. DR GO; GO:0050776; P:regulation of immune response; IMP:MGI. DR GO; GO:0045580; P:regulation of T cell differentiation; IMP:MGI. DR GO; GO:0007165; P:signal transduction; IDA:MGI. DR GO; GO:0042110; P:T cell activation; IMP:MGI. DR GO; GO:0031295; P:T cell costimulation; ISS:UniProtKB. DR GO; GO:0045061; P:thymic T cell selection; IMP:MGI. DR GO; GO:0038202; P:TORC1 signaling; ISS:UniProtKB. DR InterPro; IPR001315; CARD. DR InterPro; IPR033538; CARD11. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR036034; PDZ_sf. DR PANTHER; PTHR14559:SF4; PTHR14559:SF4; 1. DR Pfam; PF00619; CARD; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR SUPFAM; SSF50156; SSF50156; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR PROSITE; PS50209; CARD; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Coiled coil; Complete proteome; KW Cytoplasm; Membrane; Phosphoprotein; Reference proteome. FT CHAIN 1 1159 Caspase recruitment domain-containing FT protein 11. FT /FTId=PRO_0000320102. FT DOMAIN 18 110 CARD. {ECO:0000255|PROSITE- FT ProRule:PRU00046}. FT DOMAIN 672 760 PDZ. FT DOMAIN 978 1145 Guanylate kinase-like. FT COILED 176 449 {ECO:0000255}. FT COMPBIAS 623 627 Poly-Ser. FT MOD_RES 448 448 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9BXL7}. FT MOD_RES 466 466 Phosphoserine. FT {ECO:0000244|PubMed:21183079}. FT MOD_RES 512 512 Phosphoserine. FT {ECO:0000244|PubMed:21183079}. FT MOD_RES 540 540 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9BXL7}. FT MOD_RES 564 564 Phosphoserine; by PKC/PRKCB and FT PKC/PRKCQ. {ECO:0000269|PubMed:16356855}. FT MOD_RES 598 598 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9BXL7}. FT MOD_RES 649 649 Phosphoserine; by PKC/PRKCB and FT PKC/PRKCQ. {ECO:0000269|PubMed:16356855}. FT MOD_RES 657 657 Phosphoserine; by PKC/PRKCB and FT PKC/PRKCQ. {ECO:0000269|PubMed:16356855}. FT MOD_RES 891 891 Phosphoserine. FT {ECO:0000244|PubMed:21183079}. FT MOD_RES 930 930 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9BXL7}. FT VAR_SEQ 524 528 Missing (in isoform 2). FT {ECO:0000303|PubMed:15449545, FT ECO:0000303|PubMed:15489334}. FT /FTId=VSP_031595. FT CONFLICT 258 258 E -> Q (in Ref. 1; AAN10150). FT {ECO:0000305}. FT CONFLICT 860 860 R -> L (in Ref. 4; BAC29910). FT {ECO:0000305}. FT HELIX 24 27 {ECO:0000244|PDB:4I16}. FT HELIX 30 36 {ECO:0000244|PDB:4I16}. FT HELIX 39 48 {ECO:0000244|PDB:4I16}. FT HELIX 54 61 {ECO:0000244|PDB:4I16}. FT TURN 70 73 {ECO:0000244|PDB:4I16}. FT HELIX 74 80 {ECO:0000244|PDB:4I16}. FT HELIX 84 98 {ECO:0000244|PDB:4I16}. FT HELIX 100 107 {ECO:0000244|PDB:4I16}. SQ SEQUENCE 1159 AA; 134040 MW; 2ED53905B99DD94E CRC64; MPGGGPAMDD YMETLKDEEE ALWDNVECNR HMLSRYINPA KLTPYLRQCK VIDEQDEDEV LNAPMLPSKI NRAGRLLDIL HTKGQRGYVV FLESLEFYYP ELYKLVTGKE PTRRFSTIVV EEGHEGLTHF LMNEVIKLQQ QVKAKDLQRC ELLAKSRQLE DEKKQLSLIR VELLTFQERY YKMKEERDSY NDELVKVKDD NYNLAMRYAQ LSEEKNMAVM RSRDLQLEID QLKHRLNKME EECKLERNQS LKLKNDIENR PRKEQVLELE RENEMLKTKI QELQSIIQAG KRSLPDSDKA ILDILEHDRK EALEDRQELV NKIYNLQEEV RQAEELRDKY LEEKEDLELK CSTLGKDCEM YKHRMNTVML QLEEVERERD QAFHSRDEAQ TQYSQCLIEK DKYRKQIREL EEKNDEMRIE MVRREACIVN LESKLRRLSK DNGSLDQSLP RHLPATIISQ NLGDTSPRTN GQEADDSSTS EESPEDSKYF LPYHPPRRRM NLKGIQLQRA KSPISMKQAS EFQALMRTVK GHEEDFTDGS PSSSRSLPVT SSFSKMQPHR SRSSIMSITA EPPGNDSIVR RCKEDAPHRS TVEEDNDSCG FDALDLDDEN HERYSFGPPS IHSSSSSHQS EGLDAYDLEQ VNLMLRKFSL ERPFRPSVTS GGHVRGTGPL VQHTTLNGDG LITQLTLLGG NARGSFIHSV KPGSLAERAG LREGHQLLLL EGCIRGERQS VPLDACTKEE ARWTIQRCSG LITLHYKVNH EGYRKLLKEM EDGLITSGDS FYIRLNLNIS SQLDACSMSL KCDDVVHVLD TMYQDRHEWL CARVDPFTDQ DLDTGTIPSY SRAQQLLLVK LQRLVHRGNR EEADSAHHTL RSLRNTLQPE EMLSTSDPRV SPRLSRASFF FGQLLQFVSR SENKYKRMNS NERVRIISGS PLGSLSRSSL DATKLLTEKH EELDPENELS RNLTLIPYSL VRAFHCERRR PVLFTPTMLA KTLVQKLLNS GGAMEFTICK SDIVTRDEFL RKQKTETIIY SREKNPNTFE CIVPANIEAV AAKNKHCLLE AGIGCVRDLI KCKVYPIVLL IRVSEKNIKR FRKLLPRPET EEEFLRVCRL KEKELEALPC LYATVEAEMW SSVEELLRVL KDKIVEEQRK TIWVDEDQL // ID CAR18_HUMAN Reviewed; 90 AA. AC P57730; A2RRF8; DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2001, sequence version 1. DT 20-JUN-2018, entry version 129. DE RecName: Full=Caspase recruitment domain-containing protein 18; DE AltName: Full=Caspase-1 inhibitor Iceberg; GN Name=CARD18; Synonyms=ICEBERG; ORFNames=UNQ5804/PRO19611; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], STRUCTURE BY NMR, FUNCTION, INTERACTION RP WITH CASP1, INDUCTION, AND TISSUE SPECIFICITY. RX PubMed=11051551; DOI=10.1016/S0092-8674(00)00108-2; RA Humke E.W., Shriver S.K., Starovasnik M.A., Fairbrother W.J., RA Dixit V.M.; RT "ICEBERG: a novel inhibitor of interleukin-1beta generation."; RL Cell 103:99-111(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., RA Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale RT effort to identify novel human secreted and transmembrane proteins: a RT bioinformatics assessment."; RL Genome Res. 13:2265-2270(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP INTERACTION WITH CARD8. RX PubMed=11821383; DOI=10.1074/jbc.M107811200; RA Razmara M., Srinivasula S.M., Wang L., Poyet J.-L., Geddes B.J., RA DiStefano P.S., Bertin J., Alnemri E.S.; RT "CARD-8 protein, a new CARD family member that regulates caspase-1 RT activation and apoptosis."; RL J. Biol. Chem. 277:13952-13958(2002). CC -!- FUNCTION: Inhibits generation of IL-1-beta by interacting with CC caspase-1 and preventing its association with RIP2. Down-regulates CC the release of IL1B. {ECO:0000269|PubMed:11051551}. CC -!- SUBUNIT: Interacts with pro-CASP1. Interacts with CARD8. CC {ECO:0000269|PubMed:11051551, ECO:0000269|PubMed:11821383}. CC -!- INTERACTION: CC P29466:CASP1; NbExp=3; IntAct=EBI-16203975, EBI-516667; CC -!- TISSUE SPECIFICITY: Primarily expressed in the heart and placenta. CC {ECO:0000269|PubMed:11051551}. CC -!- INDUCTION: Up-regulated in response to TNF and bacterial CC lipopolysaccharides (LPS). {ECO:0000269|PubMed:11051551}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AF208005; AAG23528.1; -; mRNA. DR EMBL; AY358231; AAQ88598.1; -; mRNA. DR EMBL; BC131610; AAI31611.1; -; mRNA. DR CCDS; CCDS53705.1; -. DR RefSeq; NP_067546.1; NM_021571.3. DR UniGene; Hs.56279; -. DR PDB; 1DGN; NMR; -; A=2-90. DR PDBsum; 1DGN; -. DR ProteinModelPortal; P57730; -. DR SMR; P57730; -. DR DIP; DIP-41317N; -. DR IntAct; P57730; 1. DR STRING; 9606.ENSP00000436691; -. DR iPTMnet; P57730; -. DR PhosphoSitePlus; P57730; -. DR BioMuta; CARD18; -. DR DMDM; 12230142; -. DR PaxDb; P57730; -. DR PeptideAtlas; P57730; -. DR PRIDE; P57730; -. DR ProteomicsDB; 57022; -. DR Ensembl; ENST00000530950; ENSP00000436691; ENSG00000255501. DR GeneID; 59082; -. DR KEGG; hsa:59082; -. DR UCSC; uc021qpy.2; human. DR CTD; 59082; -. DR DisGeNET; 59082; -. DR EuPathDB; HostDB:ENSG00000255501.1; -. DR GeneCards; CARD18; -. DR HGNC; HGNC:28861; CARD18. DR HPA; HPA038582; -. DR MIM; 605354; gene. DR neXtProt; NX_P57730; -. DR OpenTargets; ENSG00000255501; -. DR PharmGKB; PA164717642; -. DR eggNOG; KOG3573; Eukaryota. DR eggNOG; ENOG410ZQIE; LUCA. DR GeneTree; ENSGT00510000049857; -. DR HOVERGEN; HBG006113; -. DR InParanoid; P57730; -. DR KO; K12806; -. DR OMA; EDMNKVR; -. DR OrthoDB; EOG091G10JS; -. DR PhylomeDB; P57730; -. DR EvolutionaryTrace; P57730; -. DR GenomeRNAi; 59082; -. DR PRO; PR:P57730; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; ENSG00000255501; -. DR CleanEx; HS_CARD18; -. DR ExpressionAtlas; P57730; baseline and differential. DR Genevisible; P57730; HS. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0050700; F:CARD domain binding; IPI:UniProtKB. DR GO; GO:0089720; F:caspase binding; IPI:UniProtKB. DR GO; GO:0097200; F:cysteine-type endopeptidase activity involved in execution phase of apoptosis; IBA:GO_Central. DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW. DR GO; GO:0097194; P:execution phase of apoptosis; IBA:GO_Central. DR GO; GO:0006954; P:inflammatory response; NAS:UniProtKB. DR GO; GO:0097340; P:inhibition of cysteine-type endopeptidase activity; IDA:UniProtKB. DR GO; GO:0050713; P:negative regulation of interleukin-1 beta secretion; IDA:UniProtKB. DR GO; GO:0032091; P:negative regulation of protein binding; IDA:UniProtKB. DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro. DR InterPro; IPR001315; CARD. DR InterPro; IPR011029; DEATH-like_dom_sf. DR Pfam; PF00619; CARD; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR PROSITE; PS50209; CARD; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Protease inhibitor; KW Reference proteome; Thiol protease inhibitor. FT CHAIN 1 90 Caspase recruitment domain-containing FT protein 18. FT /FTId=PRO_0000084145. FT DOMAIN 1 90 CARD. {ECO:0000255|PROSITE- FT ProRule:PRU00046}. FT HELIX 5 8 {ECO:0000244|PDB:1DGN}. FT HELIX 10 14 {ECO:0000244|PDB:1DGN}. FT HELIX 19 32 {ECO:0000244|PDB:1DGN}. FT HELIX 37 44 {ECO:0000244|PDB:1DGN}. FT HELIX 50 63 {ECO:0000244|PDB:1DGN}. FT HELIX 66 79 {ECO:0000244|PDB:1DGN}. FT HELIX 83 87 {ECO:0000244|PDB:1DGN}. SQ SEQUENCE 90 AA; 10138 MW; 7E74C74263367101 CRC64; MADQLLRKKR RIFIHSVGAG TINALLDCLL EDEVISQEDM NKVRDENDTV MDKARVLIDL VTGKGPKSCC KFIKHLCEED PQLASKMGLH // ID CARD8_HUMAN Reviewed; 431 AA. AC Q9Y2G2; B5KVR6; B7Z496; B7Z4A2; E9PEM7; G3XAM9; Q6PGP8; Q96P82; DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 18-JUL-2018, entry version 165. DE RecName: Full=Caspase recruitment domain-containing protein 8; DE AltName: Full=Apoptotic protein NDPP1; DE AltName: Full=CARD-inhibitor of NF-kappa-B-activating ligand; DE Short=CARDINAL; DE AltName: Full=DACAR; DE AltName: Full=Tumor up-regulated CARD-containing antagonist of CASP9; DE Short=TUCAN; GN Name=CARD8; Synonyms=KIAA0955, NDPP1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=10231032; DOI=10.1093/dnares/6.1.63; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., RA Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIII. RT The complete sequences of 100 new cDNA clones from brain which code RT for large proteins in vitro."; RL DNA Res. 6:63-70(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH CARD16 RP AND CARD18. RX PubMed=11821383; DOI=10.1074/jbc.M107811200; RA Razmara M., Srinivasula S.M., Wang L., Poyet J.-L., Geddes B.J., RA DiStefano P.S., Bertin J., Alnemri E.S.; RT "CARD-8 protein, a new CARD family member that regulates caspase-1 RT activation and apoptosis."; RL J. Biol. Chem. 277:13952-13958(2002). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=11956601; RA Zhang H., Fu W.; RT "NDPP1 is a novel CARD domain containing protein which can inhibit RT apoptosis and suppress NF-kappaB activation."; RL Int. J. Oncol. 20:1035-1040(2002). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Guiet C., Vito P.; RT "DACAR, a novel CARD-containing protein."; RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=11551959; DOI=10.1074/jbc.M107373200; RA Bouchier-Hayes L., Conroy H., Egan H., Adrain C., Creagh E.M., RA MacFarlane M., Martin S.J.; RT "CARDINAL, a novel caspase recruitment domain protein, is an inhibitor RT of multiple NF-kappa B activation pathways."; RL J. Biol. Chem. 276:44069-44077(2001). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), AND ALTERNATIVE SPLICING. RX PubMed=18212821; DOI=10.1038/sj.ejhg.5201996; RA Bagnall R.D., Roberts R.G., Mirza M.M., Torigoe T., Prescott N.J., RA Mathew C.G.; RT "Novel isoforms of the CARD8 (TUCAN) gene evade a nonsense mutation."; RL Eur. J. Hum. Genet. 16:619-625(2008). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Kidney; RA Guo J.H., Yu L.; RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), AND RP VARIANTS VAL-68 AND ALA-99. RC TISSUE=Umbilical cord blood; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M., RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Eye; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [12] RP PROTEIN SEQUENCE OF 178-198, AUTOCATALYTIC CLEAVAGE, AND MUTAGENESIS RP OF GLU-135; GLU-137; HIS-147; HIS-164; GLU-173; HIS-174; SER-189; RP PHE-190; SER-191 AND HIS-227. RX PubMed=22087307; DOI=10.1371/journal.pone.0027396; RA D'Osualdo A., Weichenberger C.X., Wagner R.N., Godzik A., Wooley J., RA Reed J.C.; RT "CARD8 and NLRP1 undergo autoproteolytic processing through a ZU5-like RT domain."; RL PLoS ONE 6:E27396-E27396(2011). RN [13] RP CHARACTERIZATION. RX PubMed=11408476; DOI=10.1074/jbc.M100433200; RA Pathan N., Marusawa H., Krajewska M., Matsuzawa S., Kim H., Okada K., RA Torii S., Kitada S., Krajewski S., Welsh K., Pio F., Godzik A., RA Reed J.C.; RT "TUCAN, an antiapoptotic caspase-associated recruitment domain family RT protein overexpressed in cancer."; RL J. Biol. Chem. 276:32220-32229(2001). RN [14] RP CHARACTERIZATION, AND MUTAGENESIS OF LEU-366. RX PubMed=12067710; DOI=10.1016/S0014-5793(02)02869-7; RA Stilo R., Leonardi A., Formisano L., Di Jeso B., Vito P., Liguoro D.; RT "TUCAN/CARDINAL and DRAL participate in a common pathway for RT modulation of NF-kappaB activation."; RL FEBS Lett. 521:165-169(2002). RN [15] RP INTERACTION WITH NALP2, AND SUBCELLULAR LOCATION. RX PubMed=15030775; DOI=10.1016/S1074-7613(04)00046-9; RA Agostini L., Martinon F., Burns K., McDermott M.F., Hawkins P.N., RA Tschopp J.; RT "NALP3 forms an IL-1beta-processing inflammasome with increased RT activity in Muckle-Wells autoinflammatory disorder."; RL Immunity 20:319-325(2004). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.46 ANGSTROMS) OF 345-431. RX PubMed=23695559; DOI=10.1107/S1744309113010075; RA Jin T., Huang M., Smith P., Jiang J., Xiao T.S.; RT "The structure of the CARD8 caspase-recruitment domain suggests its RT association with the FIIND domain and procaspases through adjacent RT surfaces."; RL Acta Crystallogr. F 69:482-487(2013). CC -!- FUNCTION: Inhibits NF-kappa-B activation. May participate in a CC regulatory mechanism that coordinates cellular responses CC controlled by NF-kappa-B transcription factor. May be a component CC of the inflammasome, a protein complex which also includes PYCARD, CC NALP2 and CASP1 and whose function would be the activation of CC proinflammatory caspases. CC -!- SUBUNIT: May form homodimers. Interacts with NEMO and DRAL. Binds CC to caspase-1, CARD16/pseudo-ICE and CARD18/ICEBERG. Interacts with CC FNBP3 (By similarity). Interacts with NALP2 NACHT domain. CC {ECO:0000250, ECO:0000269|PubMed:11821383, CC ECO:0000269|PubMed:15030775}. CC -!- INTERACTION: CC Self; NbExp=2; IntAct=EBI-2808370, EBI-2808370; CC Q14192:FHL2; NbExp=2; IntAct=EBI-2808370, EBI-701903; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15030775}. CC Nucleus {ECO:0000269|PubMed:15030775}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; Synonyms=Long; CC IsoId=Q9Y2G2-1; Sequence=Displayed; CC Name=2; Synonyms=Short; CC IsoId=Q9Y2G2-2; Sequence=VSP_000782, VSP_000783; CC Name=3; CC IsoId=Q9Y2G2-3; Sequence=VSP_012770, VSP_012771, VSP_000782, CC VSP_000783; CC Name=4; CC IsoId=Q9Y2G2-4; Sequence=VSP_045253, VSP_012771; CC Note=No experimental confirmation available.; CC Name=5; Synonyms=T60; CC IsoId=Q9Y2G2-5; Sequence=VSP_012770, VSP_012771; CC Note=Ref.6 (ABW96891) sequence is in conflict in position: CC 84:D->G. Ref.6 (ABW96891) sequence is in conflict in position: CC 107:E->D. {ECO:0000305}; CC -!- TISSUE SPECIFICITY: High expression in lung, ovary, testis and CC placenta. Lower expression in heart, kidney and liver. Also CC expressed in spleen, lymph node and bone marrow. CC -!- SEQUENCE CAUTION: CC Sequence=BAA76799.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/CARD8ID913ch19q13.html"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AB023172; BAA76799.2; ALT_INIT; mRNA. DR EMBL; AF322184; AAG50014.1; -; mRNA. DR EMBL; AF331519; AAK01126.1; -; mRNA. DR EMBL; AY026322; AAK08982.1; -; mRNA. DR EMBL; AF405558; AAL02427.1; -; mRNA. DR EMBL; EU118120; ABW96891.1; -; mRNA. DR EMBL; AF511652; AAM46959.1; -; mRNA. DR EMBL; AK297045; BAH12482.1; -; mRNA. DR EMBL; AK297069; BAH12488.1; -; mRNA. DR EMBL; AC008392; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC011466; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471177; EAW52321.1; -; Genomic_DNA. DR EMBL; CH471177; EAW52323.1; -; Genomic_DNA. DR EMBL; BC056891; AAH56891.1; -; mRNA. DR CCDS; CCDS12712.2; -. [Q9Y2G2-4] DR CCDS; CCDS54288.1; -. [Q9Y2G2-3] DR CCDS; CCDS54289.1; -. [Q9Y2G2-5] DR RefSeq; NP_001171829.1; NM_001184900.1. [Q9Y2G2-5] DR RefSeq; NP_001171830.1; NM_001184901.1. [Q9Y2G2-4] DR RefSeq; NP_001171831.1; NM_001184902.1. [Q9Y2G2-3] DR RefSeq; NP_001171832.1; NM_001184903.1. [Q9Y2G2-3] DR RefSeq; NP_055774.2; NM_014959.3. [Q9Y2G2-4] DR RefSeq; XP_006723154.1; XM_006723091.3. [Q9Y2G2-5] DR RefSeq; XP_006723155.1; XM_006723092.3. [Q9Y2G2-5] DR RefSeq; XP_006723156.1; XM_006723093.3. [Q9Y2G2-5] DR RefSeq; XP_006723158.1; XM_006723095.3. DR RefSeq; XP_006723159.1; XM_006723096.3. [Q9Y2G2-4] DR RefSeq; XP_006723160.1; XM_006723097.3. [Q9Y2G2-4] DR RefSeq; XP_006723167.1; XM_006723104.3. [Q9Y2G2-1] DR RefSeq; XP_006723169.1; XM_006723106.3. [Q9Y2G2-3] DR RefSeq; XP_006723172.1; XM_006723109.3. [Q9Y2G2-2] DR RefSeq; XP_011524943.1; XM_011526641.2. [Q9Y2G2-5] DR RefSeq; XP_011524944.1; XM_011526642.2. DR RefSeq; XP_011524945.1; XM_011526643.2. [Q9Y2G2-5] DR RefSeq; XP_011524946.1; XM_011526644.2. [Q9Y2G2-5] DR RefSeq; XP_011524952.1; XM_011526650.2. [Q9Y2G2-3] DR RefSeq; XP_016881972.1; XM_017026483.1. [Q9Y2G2-4] DR RefSeq; XP_016881979.1; XM_017026490.1. [Q9Y2G2-3] DR RefSeq; XP_016881987.1; XM_017026498.1. [Q9Y2G2-2] DR UniGene; Hs.446146; -. DR UniGene; Hs.655940; -. DR UniGene; Hs.68846; -. DR PDB; 4IKM; X-ray; 2.46 A; A=345-431. DR PDBsum; 4IKM; -. DR ProteinModelPortal; Q9Y2G2; -. DR SMR; Q9Y2G2; -. DR BioGrid; 116564; 45. DR CORUM; Q9Y2G2; -. DR IntAct; Q9Y2G2; 7. DR MINT; Q9Y2G2; -. DR STRING; 9606.ENSP00000375767; -. DR MEROPS; S79.001; -. DR iPTMnet; Q9Y2G2; -. DR PhosphoSitePlus; Q9Y2G2; -. DR BioMuta; CARD8; -. DR DMDM; 14424229; -. DR EPD; Q9Y2G2; -. DR PaxDb; Q9Y2G2; -. DR PeptideAtlas; Q9Y2G2; -. DR PRIDE; Q9Y2G2; -. DR ProteomicsDB; 85761; -. DR ProteomicsDB; 85762; -. [Q9Y2G2-2] DR ProteomicsDB; 85763; -. [Q9Y2G2-3] DR Ensembl; ENST00000391898; ENSP00000375767; ENSG00000105483. [Q9Y2G2-5] DR Ensembl; ENST00000447740; ENSP00000391248; ENSG00000105483. [Q9Y2G2-4] DR Ensembl; ENST00000519940; ENSP00000428883; ENSG00000105483. [Q9Y2G2-5] DR Ensembl; ENST00000520015; ENSP00000430747; ENSG00000105483. [Q9Y2G2-3] DR Ensembl; ENST00000520153; ENSP00000428736; ENSG00000105483. [Q9Y2G2-4] DR Ensembl; ENST00000520753; ENSP00000429839; ENSG00000105483. [Q9Y2G2-3] DR Ensembl; ENST00000521613; ENSP00000427858; ENSG00000105483. [Q9Y2G2-4] DR GeneID; 22900; -. DR KEGG; hsa:22900; -. DR UCSC; uc002pih.5; human. [Q9Y2G2-1] DR CTD; 22900; -. DR DisGeNET; 22900; -. DR EuPathDB; HostDB:ENSG00000105483.16; -. DR GeneCards; CARD8; -. DR H-InvDB; HIX0020041; -. DR HGNC; HGNC:17057; CARD8. DR HPA; HPA042071; -. DR HPA; HPA043513; -. DR MIM; 609051; gene. DR neXtProt; NX_Q9Y2G2; -. DR OpenTargets; ENSG00000105483; -. DR PharmGKB; PA134916154; -. DR eggNOG; KOG3573; Eukaryota. DR eggNOG; ENOG410ZQIE; LUCA. DR GeneTree; ENSGT00830000128447; -. DR HOGENOM; HOG000082406; -. DR HOVERGEN; HBG050795; -. DR InParanoid; Q9Y2G2; -. DR KO; K12801; -. DR OMA; RDPYLMS; -. DR OrthoDB; EOG091G01QH; -. DR PhylomeDB; Q9Y2G2; -. DR TreeFam; TF352798; -. DR SIGNOR; Q9Y2G2; -. DR ChiTaRS; CARD8; human. DR GeneWiki; CARD8; -. DR GenomeRNAi; 22900; -. DR PRO; PR:Q9Y2G2; -. DR Proteomes; UP000005640; Chromosome 19. DR Bgee; ENSG00000105483; -. DR CleanEx; HS_CARD8; -. DR ExpressionAtlas; Q9Y2G2; baseline and differential. DR Genevisible; Q9Y2G2; HS. DR GO; GO:0005737; C:cytoplasm; IDA:HGNC. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0072559; C:NLRP3 inflammasome complex; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:HGNC. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0050700; F:CARD domain binding; IPI:UniProtKB. DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; IDA:HGNC. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0032089; F:NACHT domain binding; IPI:HGNC. DR GO; GO:0042803; F:protein homodimerization activity; IDA:HGNC. DR GO; GO:0097340; P:inhibition of cysteine-type endopeptidase activity; IDA:UniProtKB. DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IDA:HGNC. DR GO; GO:0050713; P:negative regulation of interleukin-1 beta secretion; IDA:UniProtKB. DR GO; GO:0031665; P:negative regulation of lipopolysaccharide-mediated signaling pathway; IDA:UniProtKB. DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IMP:UniProtKB. DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB. DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0050718; P:positive regulation of interleukin-1 beta secretion; IDA:HGNC. DR InterPro; IPR001315; CARD. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR025307; FIIND_dom. DR Pfam; PF00619; CARD; 1. DR Pfam; PF13553; FIIND; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR PROSITE; PS50209; CARD; 1. DR PROSITE; PS51830; FIIND; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; Complete proteome; KW Cytoplasm; Direct protein sequencing; Nucleus; Polymorphism; KW Reference proteome. FT CHAIN 1 431 Caspase recruitment domain-containing FT protein 8. FT /FTId=PRO_0000144080. FT DOMAIN 56 340 FIIND. {ECO:0000255|PROSITE- FT ProRule:PRU01174}. FT DOMAIN 340 430 CARD. {ECO:0000255|PROSITE- FT ProRule:PRU00046}. FT SITE 190 191 Cleavage; by autolysis. FT {ECO:0000255|PROSITE-ProRule:PRU01174, FT ECO:0000269|PubMed:22087307}. FT VAR_SEQ 1 25 MMRQRQSHYCSVLFLSVNYLGGTFP -> MEKKECPEKSSS FT SEEELPRRDSGSSRNIDASKLIRLQGSRKLLVDNSIRELQY FT TKTGIFFQAEACVTNDTVYRELPCVSETLCDISHFFQEDDE FT TEAEPLLFRAVPECQLSGGDIPSVSEEQESSEGQDS (in FT isoform 3 and isoform 5). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:18212821}. FT /FTId=VSP_012770. FT VAR_SEQ 1 25 MMRQRQSHYCSVLFLSVNYLGGTFP -> MEKKECPEKSSS FT SEEELPRRVYRELPCVSETLCDISHFFQEDDETEAEPLLFR FT AVPECQLSGGDIPSVSEEQESSEGQDS (in isoform FT 4). {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_045253. FT VAR_SEQ 152 152 Q -> QA (in isoform 3, isoform 4 and FT isoform 5). {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:18212821}. FT /FTId=VSP_012771. FT VAR_SEQ 282 286 ELKLS -> WISSL (in isoform 2 and isoform FT 3). {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|Ref.7}. FT /FTId=VSP_000782. FT VAR_SEQ 287 431 Missing (in isoform 2 and isoform 3). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|Ref.7}. FT /FTId=VSP_000783. FT VARIANT 68 68 I -> V (in dbSNP:rs11881179). FT {ECO:0000269|PubMed:14702039}. FT /FTId=VAR_048606. FT VARIANT 99 99 E -> A (in dbSNP:rs59878320). FT {ECO:0000269|PubMed:14702039}. FT /FTId=VAR_061079. FT MUTAGEN 135 135 E->A: No effect on autocatalytic FT cleavage. {ECO:0000269|PubMed:22087307}. FT MUTAGEN 137 137 E->A: No effect on autocatalytic FT cleavage. {ECO:0000269|PubMed:22087307}. FT MUTAGEN 147 147 H->A: Severe loss of autocatalytic FT cleavage. {ECO:0000269|PubMed:22087307}. FT MUTAGEN 164 164 H->A: Severe loss of autocatalytic FT cleavage. {ECO:0000269|PubMed:22087307}. FT MUTAGEN 173 173 E->A: Partial loss of autocatalytic FT cleavage. {ECO:0000269|PubMed:22087307}. FT MUTAGEN 174 174 H->A: No effect on autocatalytic FT cleavage. {ECO:0000269|PubMed:22087307}. FT MUTAGEN 189 189 S->A: Partial loss of autocatalytic FT cleavage. {ECO:0000269|PubMed:22087307}. FT MUTAGEN 189 189 S->Q: No effect on autocatalytic FT cleavage. {ECO:0000269|PubMed:22087307}. FT MUTAGEN 190 190 F->H: Severe loss of autocatalytic FT cleavage. {ECO:0000269|PubMed:22087307}. FT MUTAGEN 191 191 S->A: Complete loss of autocatalytic FT cleavage. {ECO:0000269|PubMed:22087307}. FT MUTAGEN 227 227 H->A: No effect on autocatalytic FT cleavage. {ECO:0000269|PubMed:22087307}. FT MUTAGEN 366 366 L->R: Inhibits homodimer formation. FT {ECO:0000269|PubMed:12067710}. FT CONFLICT 60 60 E -> G (in Ref. 5; AAL02427). FT {ECO:0000305}. FT CONFLICT 148 148 F -> S (in Ref. 11; AAH56891). FT {ECO:0000305}. FT CONFLICT 219 219 P -> R (in Ref. 8; BAH12488). FT {ECO:0000305}. FT CONFLICT 326 326 V -> M (in Ref. 5; AAL02427). FT {ECO:0000305}. FT CONFLICT 417 417 E -> G (in Ref. 6; ABW96891). FT {ECO:0000305}. FT CONFLICT 422 422 L -> P (in Ref. 5; AAL02427). FT {ECO:0000305}. FT HELIX 345 350 {ECO:0000244|PDB:4IKM}. FT HELIX 352 358 {ECO:0000244|PDB:4IKM}. FT HELIX 363 371 {ECO:0000244|PDB:4IKM}. FT HELIX 377 385 {ECO:0000244|PDB:4IKM}. FT STRAND 386 388 {ECO:0000244|PDB:4IKM}. FT HELIX 389 401 {ECO:0000244|PDB:4IKM}. FT HELIX 405 418 {ECO:0000244|PDB:4IKM}. FT HELIX 420 424 {ECO:0000244|PDB:4IKM}. FT HELIX 427 431 {ECO:0000244|PDB:4IKM}. SQ SEQUENCE 431 AA; 48933 MW; CB54D130807732E6 CRC64; MMRQRQSHYC SVLFLSVNYL GGTFPGDICS EENQIVSSYA SKVCFEIEED YKNRQFLGPE GNVDVELIDK STNRYSVWFP TAGWYLWSAT GLGFLVRDEV TVTIAFGSWS QHLALDLQHH EQWLVGGPLF DVTAEPEEAV AEIHLPHFIS LQGEVDVSWF LVAHFKNEGM VLEHPARVEP FYAVLESPSF SLMGILLRIA SGTRLSIPIT SNTLIYYHPH PEDIKFHLYL VPSDALLTKA IDDEEDRFHG VRLQTSPPME PLNFGSSYIV SNSANLKVMP KELKLSYRSP GEIQHFSKFY AGQMKEPIQL EITEKRHGTL VWDTEVKPVD LQLVAASAPP PFSGAAFVKE NHRQLQARMG DLKGVLDDLQ DNEVLTENEK ELVEQEKTRQ SKNEALLSMV EKKGDLALDV LFRSISERDP YLVSYLRQQN L // ID CASP1_HUMAN Reviewed; 404 AA. AC P29466; B5MDZ1; Q53EY6; Q6DMQ1; Q6GSS3; Q6PI75; Q9UCN3; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1993, sequence version 1. DT 18-JUL-2018, entry version 206. DE RecName: Full=Caspase-1; DE Short=CASP-1; DE EC=3.4.22.36; DE AltName: Full=Interleukin-1 beta convertase; DE Short=IL-1BC; DE AltName: Full=Interleukin-1 beta-converting enzyme; DE Short=ICE; DE Short=IL-1 beta-converting enzyme; DE AltName: Full=p45; DE Contains: DE RecName: Full=Caspase-1 subunit p20; DE Contains: DE RecName: Full=Caspase-1 subunit p10; DE Flags: Precursor; GN Name=CASP1; Synonyms=IL1BC, IL1BCE; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), PARTIAL PROTEIN SEQUENCE, RP ACTIVE SITE, AND FUNCTION. RX PubMed=1574116; DOI=10.1038/356768a0; RA Thornberry N.A., Bull H.G., Calaycay J.R., Chapman K.T., Howard A.D., RA Kostura M.J., Miller D.K., Molineaux S.M., Weidner J.R., Aunins J., RA Elliston K.O., Ayala J.M., Casano F.J., Chin J., Ding G.J.-F., RA Egger L.A., Gaffney E.P., Limjuco G., Palyha O.C., Raju M., RA Rolando A.M., Salley J.P., Yamin T.-T., Lee T.D., Shively J.E., RA McCross M., Mumford R.A., Schmidt J.A., Tocci M.J.; RT "A novel heterodimeric cysteine protease is required for interleukin-1 RT beta processing in monocytes."; RL Nature 356:768-774(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), AND PROTEIN SEQUENCE OF RP 120-142. RX PubMed=1373520; DOI=10.1126/science.1373520; RA Cerretti D.P., Kozlosky C.J., Mosley B., Nelson N., van Ness K., RA Greenstreet T.A., March C.J., Kronheim S.R., Druck T., RA Cannizzaro L.A., Huebner K., Black R.A.; RT "Molecular cloning of the interleukin-1 beta converting enzyme."; RL Science 256:97-100(1992). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS BETA; DELTA; EPSILON AND GAMMA), RP ALTERNATIVE SPLICING, AND FUNCTION. RX PubMed=7876192; DOI=10.1074/jbc.270.9.4312; RA Alnemri E.S., Fernandes-Alnemri T., Litwack G.; RT "Cloning and expression of four novel isoforms of human interleukin-1 RT beta converting enzyme with different apoptotic activities."; RL J. Biol. Chem. 270:4312-4317(1995). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA). RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S., RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., RA Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GAMMA), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 4-404 (ISOFORM BETA). RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 32-404 (ISOFORM ALPHA), FUNCTION, RP MUTAGENESIS OF CYS-285, ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY. RX PubMed=15498465; DOI=10.1016/j.ygeno.2004.06.005; RA Feng Q., Li P., Leung P.C.K., Auersperg N.; RT "Caspase-1 zeta, a new splice variant of caspase-1 gene."; RL Genomics 84:587-591(2004). RN [8] RP PROTEIN SEQUENCE OF 120-142. RX PubMed=1321594; DOI=10.1016/0003-9861(92)90629-B; RA Kronheim S.R., Mumma A., Greenstreet T., Glackin P.J., Van Ness K., RA March C.J., Black R.A.; RT "Purification of interleukin-1 beta converting enzyme, the protease RT that cleaves the interleukin-1 beta precursor."; RL Arch. Biochem. Biophys. 296:698-703(1992). RN [9] RP INTERACTION WITH CARD18. RX PubMed=11051551; DOI=10.1016/S0092-8674(00)00108-2; RA Humke E.W., Shriver S.K., Starovasnik M.A., Fairbrother W.J., RA Dixit V.M.; RT "ICEBERG: a novel inhibitor of interleukin-1beta generation."; RL Cell 103:99-111(2000). RN [10] RP COMPONENT OF THE INFLAMMASOME. RX PubMed=15030775; DOI=10.1016/S1074-7613(04)00046-9; RA Agostini L., Martinon F., Burns K., McDermott M.F., Hawkins P.N., RA Tschopp J.; RT "NALP3 forms an IL-1beta-processing inflammasome with increased RT activity in Muckle-Wells autoinflammatory disorder."; RL Immunity 20:319-325(2004). RN [11] RP INTERACTION WITH CARD17. RX PubMed=15383541; DOI=10.1074/jbc.M407891200; RA Lamkanfi M., Denecker G., Kalai M., D'hondt K., Meeus A., Declercq W., RA Saelens X., Vandenabeele P.; RT "INCA, a novel human caspase recruitment domain protein that inhibits RT interleukin-1beta generation."; RL J. Biol. Chem. 279:51729-51738(2004). RN [12] RP INTERACTION WITH MEFV. RX PubMed=16785446; DOI=10.1073/pnas.0602081103; RA Chae J.J., Wood G., Masters S.L., Richard K., Park G., Smith B.J., RA Kastner D.L.; RT "The B30.2 domain of pyrin, the familial Mediterranean fever protein, RT interacts directly with caspase-1 to modulate IL-1beta production."; RL Proc. Natl. Acad. Sci. U.S.A. 103:9982-9987(2006). RN [13] RP INDUCTION BY M.TUBERCULOSIS. RC TISSUE=Macrophage; RX PubMed=20148899; DOI=10.1111/j.1462-5822.2010.01450.x; RA Mishra B.B., Moura-Alves P., Sonawane A., Hacohen N., Griffiths G., RA Moita L.F., Anes E.; RT "Mycobacterium tuberculosis protein ESAT-6 is a potent activator of RT the NLRP3/ASC inflammasome."; RL Cell. Microbiol. 12:1046-1063(2010). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [15] RP FUNCTION. RX PubMed=28314590; DOI=10.1016/j.immuni.2017.02.011; RA Wang Y., Ning X., Gao P., Wu S., Sha M., Lv M., Zhou X., Gao J., RA Fang R., Meng G., Su X., Jiang Z.; RT "Inflammasome activation triggers caspase-1-mediated cleavage of cGAS RT to regulate responses to DNA virus infection."; RL Immunity 46:393-404(2017). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), AND SUBUNIT. RX PubMed=8044845; DOI=10.1016/0092-8674(94)90303-4; RA Walker N.P.C., Talanian R.V., Brady K.D., Dang L.C., Bump N.J., RA Ferenz C.R., Franklin S., Ghayur T., Hackett M.C., Hammill L.D., RA Herzog L., Hugunin M., Houy W., Mankovich J.A., McGuiness L., RA Orlewicz E., Paskind M., Pratt C.A., Reis P., Summani A., RA Terranova M., Welch J.P., Xiong L., Moeller A., Tracey D.E., Kamen R., RA Wong W.W.; RT "Crystal structure of the cysteine protease interleukin-1 beta- RT converting enzyme: a (p20/p10)2 homodimer."; RL Cell 78:343-352(1994). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.73 ANGSTROMS). RX PubMed=9190289; DOI=10.1016/S1074-5521(97)90258-1; RA Rano T.A., Timkey T., Peterson E.P., Rotonda J., Nicholson D.W., RA Becker J.W., Chapman K.T., Thornberry N.A.; RT "A combinatorial approach for determining protease specificities: RT application to interleukin-1beta converting enzyme (ICE)."; RL Chem. Biol. 4:149-155(1997). RN [18] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH INHIBITORS. RX PubMed=9987822; DOI=10.1248/cpb.47.11; RA Okamoto Y., Anan H., Nakai E., Morihira K., Yonetoku Y., Kurihara H., RA Sakashita H., Terai Y., Takeuchi M., Shibanuma T., Isomura Y.; RT "Peptide based interleukin-1 beta converting enzyme (ICE) inhibitors: RT synthesis, structure activity relationships and crystallographic study RT of the ICE-inhibitor complex."; RL Chem. Pharm. Bull. 47:11-21(1999). RN [19] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 120-404 OF MUTANT ALA-285. RX PubMed=15296730; DOI=10.1016/j.str.2004.05.010; RA Romanowski M.J., Scheer J.M., O'Brien T., McDowell R.S.; RT "Crystal structures of a ligand-free and malonate-bound human caspase- RT 1: implications for the mechanism of substrate binding."; RL Structure 12:1361-1371(2004). CC -!- FUNCTION: Thiol protease that cleaves IL-1 beta between an Asp and CC an Ala, releasing the mature cytokine which is involved in a CC variety of inflammatory processes. Important for defense against CC pathogens. Cleaves and activates sterol regulatory element binding CC proteins (SREBPs). Can also promote apoptosis. Upon inflammasome CC activation, during DNA virus infection but not RNA virus CC challenge, controls antiviral immunity through the cleavage of CC CGAS, rendering it inactive (PubMed:28314590). CC {ECO:0000269|PubMed:15498465, ECO:0000269|PubMed:1574116, CC ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:7876192}. CC -!- CATALYTIC ACTIVITY: Strict requirement for an Asp residue at CC position P1 and has a preferred cleavage sequence of Tyr-Val-Ala- CC Asp-|-. CC -!- ENZYME REGULATION: Specifically inhibited by the cowpox virus Crma CC protein. CC -!- SUBUNIT: Heterotetramer that consists of two anti-parallel CC arranged heterodimers, each one formed by a 20 kDa (p20) and a 10 CC kDa (p10) subunit. The p20 subunit can also form a heterodimer CC with the epsilon isoform which then has an inhibitory effect. May CC be a component of the inflammasome, a protein complex which also CC includes PYCARD, CARD8 and NALP2 and whose function would be the CC activation of proinflammatory caspases. Both the p10 and p20 CC subunits interact with MEFV. Interacts with CARD17/INCA and CC CARD18. {ECO:0000269|PubMed:11051551, ECO:0000269|PubMed:15383541, CC ECO:0000269|PubMed:16785446, ECO:0000269|PubMed:8044845, CC ECO:0000269|PubMed:9987822}. CC -!- INTERACTION: CC Self; NbExp=2; IntAct=EBI-516667, EBI-516667; CC Q5XLA6:CARD17; NbExp=3; IntAct=EBI-516667, EBI-16203934; CC P57730:CARD18; NbExp=3; IntAct=EBI-516667, EBI-16203975; CC P09038:FGF2; NbExp=2; IntAct=EBI-516667, EBI-977447; CC P01583:IL1A; NbExp=3; IntAct=EBI-516667, EBI-1749782; CC O15553:MEFV; NbExp=2; IntAct=EBI-516667, EBI-7644532; CC O15553-2:MEFV; NbExp=3; IntAct=EBI-516667, EBI-15588296; CC Q9NPP4:NLRC4; NbExp=4; IntAct=EBI-516667, EBI-1222527; CC Q9C000:NLRP1; NbExp=3; IntAct=EBI-516667, EBI-1220518; CC Q9HC29:NOD2; NbExp=4; IntAct=EBI-516667, EBI-7445625; CC Q9ULZ3:PYCARD; NbExp=9; IntAct=EBI-516667, EBI-751215; CC P58753-2:TIRAP; NbExp=5; IntAct=EBI-516667, EBI-528654; CC Q08AM6:VAC14; NbExp=3; IntAct=EBI-516667, EBI-2107455; CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Comment=Additional isoforms seem to exist.; CC Name=Alpha; CC IsoId=P29466-1; Sequence=Displayed; CC Name=Beta; CC IsoId=P29466-2; Sequence=VSP_000798; CC Name=Gamma; CC IsoId=P29466-3; Sequence=VSP_000799; CC Name=Delta; CC IsoId=P29466-4; Sequence=VSP_000799, VSP_000800; CC Note=Apoptosis inactive.; CC Name=Epsilon; CC IsoId=P29466-5; Sequence=VSP_000797; CC Note=Apoptosis inactive.; CC -!- TISSUE SPECIFICITY: Expressed in larger amounts in spleen and CC lung. Detected in liver, heart, small intestine, colon, thymus, CC prostate, skeletal muscle, peripheral blood leukocytes, kidney and CC testis. No expression in the brain. {ECO:0000269|PubMed:15498465}. CC -!- INDUCTION: Transcription and translation induced by M.tuberculosis CC and a number of different M.tuberculosis components; EsxA is the CC most potent activator tested (at protein level) (PubMed:20148899). CC {ECO:0000269|PubMed:20148899}. CC -!- PTM: The two subunits are derived from the precursor sequence by CC an autocatalytic mechanism. CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAT72297.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=AAT72297.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/CASP1ID145ch11q22.html"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; X65019; CAA46153.1; -; mRNA. DR EMBL; M87507; AAA66942.1; -; mRNA. DR EMBL; U13697; AAC50107.1; -; mRNA. DR EMBL; U13698; AAC50108.1; -; mRNA. DR EMBL; U13699; AAC50109.1; -; mRNA. DR EMBL; U13700; AAC50110.1; -; mRNA. DR EMBL; AK223503; BAD97223.1; -; mRNA. DR EMBL; AP001153; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC041689; AAH41689.1; -; mRNA. DR EMBL; BC062327; AAH62327.1; -; mRNA. DR EMBL; AY660536; AAT72297.1; ALT_SEQ; mRNA. DR CCDS; CCDS53704.1; -. [P29466-3] DR CCDS; CCDS8329.1; -. [P29466-2] DR CCDS; CCDS8330.1; -. [P29466-1] DR CCDS; CCDS8331.1; -. [P29466-4] DR CCDS; CCDS8332.1; -. [P29466-5] DR PIR; A54263; A42677. DR PIR; A56084; A56084. DR PIR; B56084; B56084. DR PIR; C56084; C56084. DR PIR; D56084; D56084. DR RefSeq; NP_001214.1; NM_001223.4. [P29466-2] DR RefSeq; NP_001244047.1; NM_001257118.2. [P29466-1] DR RefSeq; NP_001244048.1; NM_001257119.2. [P29466-2] DR RefSeq; NP_150634.1; NM_033292.3. [P29466-1] DR RefSeq; NP_150635.1; NM_033293.3. [P29466-3] DR RefSeq; NP_150636.1; NM_033294.3. [P29466-4] DR RefSeq; NP_150637.1; NM_033295.3. [P29466-5] DR UniGene; Hs.2490; -. DR PDB; 1BMQ; X-ray; 2.50 A; A=131-297, B=317-404. DR PDB; 1IBC; X-ray; 2.73 A; A=104-297, B=317-404. DR PDB; 1ICE; X-ray; 2.60 A; A=131-297, B=317-404. DR PDB; 1RWK; X-ray; 2.30 A; A=120-297, B=317-404. DR PDB; 1RWM; X-ray; 2.70 A; A=120-297, B=317-404. DR PDB; 1RWN; X-ray; 2.00 A; A=120-297, B=317-404. DR PDB; 1RWO; X-ray; 2.10 A; A=120-297, B=317-404. DR PDB; 1RWP; X-ray; 2.20 A; A=120-297, B=317-404. DR PDB; 1RWV; X-ray; 2.10 A; A=120-297, B=317-404. DR PDB; 1RWW; X-ray; 2.80 A; A=120-297, B=317-404. DR PDB; 1RWX; X-ray; 1.85 A; A=120-297, B=317-404. DR PDB; 1SC1; X-ray; 2.60 A; A=120-297, B=317-404. DR PDB; 1SC3; X-ray; 1.80 A; A=120-297, B=317-404. DR PDB; 1SC4; X-ray; 2.10 A; A=120-297, B=317-404. DR PDB; 2FQQ; X-ray; 3.30 A; A=120-297, B=317-404. DR PDB; 2H48; X-ray; 2.20 A; A=120-297, B=317-404. DR PDB; 2H4W; X-ray; 2.00 A; A=120-297, B=317-404. DR PDB; 2H4Y; X-ray; 1.90 A; A=120-297, B=317-404. DR PDB; 2H51; X-ray; 2.10 A; A=120-297, B=317-404. DR PDB; 2H54; X-ray; 1.80 A; A=120-297, B=317-404. DR PDB; 2HBQ; X-ray; 1.80 A; A=120-297, B=317-404. DR PDB; 2HBR; X-ray; 2.20 A; A=120-297, B=317-404. DR PDB; 2HBY; X-ray; 2.10 A; A=120-297, B=317-404. DR PDB; 2HBZ; X-ray; 1.90 A; A=120-297, B=317-404. DR PDB; 3D6F; X-ray; 1.90 A; A=120-297, B=317-404. DR PDB; 3D6H; X-ray; 2.00 A; A=120-297, B=317-404. DR PDB; 3D6M; X-ray; 1.80 A; A=120-297, B=317-404. DR PDB; 3E4C; X-ray; 2.05 A; A/B=104-404. DR PDB; 3NS7; X-ray; 2.60 A; A=136-297, B=317-404. DR PDB; 5FNA; EM; 4.80 A; A/B/C/D/E/F/G/H=2-86. DR PDB; 5MMV; X-ray; 2.15 A; A=120-297, B=317-404. DR PDB; 5MTK; X-ray; 2.53 A; A=120-297, B=317-404. DR PDB; 6F6R; X-ray; 1.80 A; A=118-297, B=317-404. DR PDBsum; 1BMQ; -. DR PDBsum; 1IBC; -. DR PDBsum; 1ICE; -. DR PDBsum; 1RWK; -. DR PDBsum; 1RWM; -. DR PDBsum; 1RWN; -. DR PDBsum; 1RWO; -. DR PDBsum; 1RWP; -. DR PDBsum; 1RWV; -. DR PDBsum; 1RWW; -. DR PDBsum; 1RWX; -. DR PDBsum; 1SC1; -. DR PDBsum; 1SC3; -. DR PDBsum; 1SC4; -. DR PDBsum; 2FQQ; -. DR PDBsum; 2H48; -. DR PDBsum; 2H4W; -. DR PDBsum; 2H4Y; -. DR PDBsum; 2H51; -. DR PDBsum; 2H54; -. DR PDBsum; 2HBQ; -. DR PDBsum; 2HBR; -. DR PDBsum; 2HBY; -. DR PDBsum; 2HBZ; -. DR PDBsum; 3D6F; -. DR PDBsum; 3D6H; -. DR PDBsum; 3D6M; -. DR PDBsum; 3E4C; -. DR PDBsum; 3NS7; -. DR PDBsum; 5FNA; -. DR PDBsum; 5MMV; -. DR PDBsum; 5MTK; -. DR PDBsum; 6F6R; -. DR ProteinModelPortal; P29466; -. DR SMR; P29466; -. DR BioGrid; 107284; 38. DR CORUM; P29466; -. DR DIP; DIP-175N; -. DR IntAct; P29466; 19. DR MINT; P29466; -. DR STRING; 9606.ENSP00000410076; -. DR BindingDB; P29466; -. DR ChEMBL; CHEMBL4801; -. DR DrugBank; DB07744; 3-[2-(2-BENZYLOXYCARBONYLAMINO-3-METHYL-BUTYRYLAMINO)-PROPIONYLAMINO]-4-OXO-PENTANOIC ACID. DR DrugBank; DB07916; 3-{6-[(8-HYDROXY-QUINOLINE-2-CARBONYL)-AMINO]-2-THIOPHEN-2-YL-HEXANOYLAMINO}-4-OXO-BUTYRI ACID. DR DrugBank; DB05408; IDN-6556. DR DrugBank; DB05301; LAX-101. DR DrugBank; DB01017; Minocycline. DR DrugBank; DB04875; Pralnacasan. DR DrugBank; DB05507; VX-765. DR GuidetoPHARMACOLOGY; 1617; -. DR iPTMnet; P29466; -. DR PhosphoSitePlus; P29466; -. DR BioMuta; CASP1; -. DR DMDM; 266321; -. DR EPD; P29466; -. DR MaxQB; P29466; -. DR PaxDb; P29466; -. DR PeptideAtlas; P29466; -. DR PRIDE; P29466; -. DR ProteomicsDB; 54571; -. DR ProteomicsDB; 54572; -. [P29466-2] DR ProteomicsDB; 54573; -. [P29466-3] DR ProteomicsDB; 54574; -. [P29466-4] DR ProteomicsDB; 54575; -. [P29466-5] DR DNASU; 834; -. DR Ensembl; ENST00000353247; ENSP00000344132; ENSG00000137752. [P29466-5] DR Ensembl; ENST00000436863; ENSP00000410076; ENSG00000137752. [P29466-1] DR Ensembl; ENST00000446369; ENSP00000403260; ENSG00000137752. [P29466-4] DR Ensembl; ENST00000525825; ENSP00000434779; ENSG00000137752. [P29466-2] DR Ensembl; ENST00000526568; ENSP00000434250; ENSG00000137752. [P29466-3] DR Ensembl; ENST00000531166; ENSP00000434303; ENSG00000137752. [P29466-5] DR Ensembl; ENST00000533400; ENSP00000433138; ENSG00000137752. [P29466-1] DR Ensembl; ENST00000534497; ENSP00000436875; ENSG00000137752. [P29466-4] DR GeneID; 834; -. DR KEGG; hsa:834; -. DR UCSC; uc001pig.5; human. [P29466-1] DR CTD; 834; -. DR DisGeNET; 834; -. DR EuPathDB; HostDB:ENSG00000137752.22; -. DR GeneCards; CASP1; -. DR HGNC; HGNC:1499; CASP1. DR HPA; CAB002685; -. DR HPA; HPA003056; -. DR MIM; 147678; gene. DR neXtProt; NX_P29466; -. DR OpenTargets; ENSG00000137752; -. DR PharmGKB; PA26083; -. DR eggNOG; KOG3573; Eukaryota. DR eggNOG; ENOG410ZQIE; LUCA. DR GeneTree; ENSGT00910000144131; -. DR HOVERGEN; HBG076981; -. DR InParanoid; P29466; -. DR KO; K01370; -. DR OMA; EYAWSCD; -. DR OrthoDB; EOG091G07NO; -. DR PhylomeDB; P29466; -. DR TreeFam; TF102023; -. DR BRENDA; 3.4.22.36; 2681. DR Reactome; R-HSA-168638; NOD1/2 Signaling Pathway. DR Reactome; R-HSA-448706; Interleukin-1 processing. DR Reactome; R-HSA-6803207; TP53 Regulates Transcription of Caspase Activators and Caspases. DR Reactome; R-HSA-844456; The NLRP3 inflammasome. DR Reactome; R-HSA-844615; The AIM2 inflammasome. DR Reactome; R-HSA-844623; The IPAF inflammasome. DR Reactome; R-HSA-9008059; Interleukin-37 signaling. DR SABIO-RK; P29466; -. DR SignaLink; P29466; -. DR SIGNOR; P29466; -. DR ChiTaRS; CASP1; human. DR EvolutionaryTrace; P29466; -. DR GeneWiki; Caspase_1; -. DR GenomeRNAi; 834; -. DR PMAP-CutDB; P29466; -. DR PRO; PR:P29466; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; ENSG00000137752; -. DR CleanEx; HS_CASP1; -. DR ExpressionAtlas; P29466; baseline and differential. DR Genevisible; P29466; HS. DR GO; GO:0097169; C:AIM2 inflammasome complex; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005576; C:extracellular region; IEA:Ensembl. DR GO; GO:0072557; C:IPAF inflammasome complex; ISS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IEA:GOC. DR GO; GO:0072558; C:NLRP1 inflammasome complex; IDA:UniProtKB. DR GO; GO:0072559; C:NLRP3 inflammasome complex; IDA:UniProtKB. DR GO; GO:0097179; C:protease inhibitor complex; IMP:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0050700; F:CARD domain binding; IPI:UniProtKB. DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; TAS:ProtInc. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:UniProtKB. DR GO; GO:0097153; F:cysteine-type endopeptidase activity involved in apoptotic process; IBA:GO_Central. DR GO; GO:0004175; F:endopeptidase activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0042802; F:identical protein binding; IMP:UniProtKB. DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB. DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc. DR GO; GO:0071345; P:cellular response to cytokine stimulus; TAS:Reactome. DR GO; GO:0071346; P:cellular response to interferon-gamma; IMP:UniProtKB. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IMP:UniProtKB. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB. DR GO; GO:0071310; P:cellular response to organic substance; IDA:MGI. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome. DR GO; GO:0032611; P:interleukin-1 beta production; IEA:Ensembl. DR GO; GO:0060081; P:membrane hyperpolarization; IEA:Ensembl. DR GO; GO:0051882; P:mitochondrial depolarization; IEA:Ensembl. DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB. DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB. DR GO; GO:0050717; P:positive regulation of interleukin-1 alpha secretion; IEA:Ensembl. DR GO; GO:0050718; P:positive regulation of interleukin-1 beta secretion; IDA:UniProtKB. DR GO; GO:1903265; P:positive regulation of tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB. DR GO; GO:0097300; P:programmed necrotic cell death; IEA:Ensembl. DR GO; GO:0016540; P:protein autoprocessing; IDA:UniProtKB. DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB. DR GO; GO:0070269; P:pyroptosis; IEA:Ensembl. DR GO; GO:0042981; P:regulation of apoptotic process; TAS:Reactome. DR GO; GO:0010506; P:regulation of autophagy; IEA:Ensembl. DR GO; GO:0050727; P:regulation of inflammatory response; IBA:GO_Central. DR GO; GO:0033198; P:response to ATP; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:1901998; P:toxin transport; IEA:Ensembl. DR CDD; cd00032; CASc; 1. DR InterPro; IPR001315; CARD. DR InterPro; IPR029030; Caspase-like_dom_sf. DR InterPro; IPR033139; Caspase_cys_AS. DR InterPro; IPR016129; Caspase_his_AS. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR002138; Pept_C14_p10. DR InterPro; IPR001309; Pept_C14_p20. DR InterPro; IPR015917; Pept_C14A. DR Pfam; PF00619; CARD; 1. DR PRINTS; PR00376; IL1BCENZYME. DR SMART; SM00114; CARD; 1. DR SMART; SM00115; CASc; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR SUPFAM; SSF52129; SSF52129; 1. DR PROSITE; PS50209; CARD; 1. DR PROSITE; PS01122; CASPASE_CYS; 1. DR PROSITE; PS01121; CASPASE_HIS; 1. DR PROSITE; PS50207; CASPASE_P10; 1. DR PROSITE; PS50208; CASPASE_P20; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; Complete proteome; KW Cytoplasm; Direct protein sequencing; Hydrolase; Phosphoprotein; KW Polymorphism; Protease; Reference proteome; Thiol protease; Zymogen. FT PROPEP 1 119 FT /FTId=PRO_0000004521. FT CHAIN 120 297 Caspase-1 subunit p20. FT /FTId=PRO_0000004522. FT PROPEP 298 316 FT /FTId=PRO_0000004523. FT CHAIN 317 404 Caspase-1 subunit p10. FT /FTId=PRO_0000004524. FT DOMAIN 1 91 CARD. {ECO:0000255|PROSITE- FT ProRule:PRU00046}. FT ACT_SITE 237 237 {ECO:0000269|PubMed:1574116}. FT ACT_SITE 285 285 {ECO:0000269|PubMed:1574116}. FT MOD_RES 302 302 Phosphoserine. FT {ECO:0000250|UniProtKB:P29452}. FT VAR_SEQ 20 335 Missing (in isoform Epsilon). FT {ECO:0000303|PubMed:7876192}. FT /FTId=VSP_000797. FT VAR_SEQ 20 112 Missing (in isoform Gamma and isoform FT Delta). {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:7876192}. FT /FTId=VSP_000799. FT VAR_SEQ 92 112 Missing (in isoform Beta). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:7876192}. FT /FTId=VSP_000798. FT VAR_SEQ 288 335 Missing (in isoform Delta). FT {ECO:0000303|PubMed:7876192}. FT /FTId=VSP_000800. FT VARIANT 15 15 R -> H (in dbSNP:rs1042743). FT /FTId=VAR_048615. FT MUTAGEN 285 285 C->A,S: Loss of activity. FT {ECO:0000269|PubMed:15498465}. FT CONFLICT 319 319 K -> R (in Ref. 4; BAD97223). FT {ECO:0000305}. FT CONFLICT 402 402 P -> L (in Ref. 4; BAD97223). FT {ECO:0000305}. FT TURN 129 132 {ECO:0000244|PDB:1SC3}. FT HELIX 138 147 {ECO:0000244|PDB:1SC3}. FT STRAND 148 150 {ECO:0000244|PDB:1SC3}. FT TURN 158 160 {ECO:0000244|PDB:1SC3}. FT STRAND 164 169 {ECO:0000244|PDB:1SC3}. FT STRAND 174 176 {ECO:0000244|PDB:1SC3}. FT HELIX 182 195 {ECO:0000244|PDB:1SC3}. FT STRAND 199 205 {ECO:0000244|PDB:1SC3}. FT HELIX 208 219 {ECO:0000244|PDB:1SC3}. FT HELIX 222 226 {ECO:0000244|PDB:1SC3}. FT STRAND 230 236 {ECO:0000244|PDB:1SC3}. FT STRAND 242 244 {ECO:0000244|PDB:1SC3}. FT STRAND 250 252 {ECO:0000244|PDB:1SC3}. FT STRAND 255 257 {ECO:0000244|PDB:1SC4}. FT HELIX 258 265 {ECO:0000244|PDB:1SC3}. FT TURN 267 269 {ECO:0000244|PDB:1SC3}. FT HELIX 271 273 {ECO:0000244|PDB:1SC3}. FT STRAND 278 283 {ECO:0000244|PDB:1SC3}. FT STRAND 287 289 {ECO:0000244|PDB:1SC3}. FT STRAND 291 298 {ECO:0000244|PDB:3E4C}. FT HELIX 316 319 {ECO:0000244|PDB:3E4C}. FT STRAND 326 333 {ECO:0000244|PDB:1SC3}. FT STRAND 340 342 {ECO:0000244|PDB:2H54}. FT TURN 343 345 {ECO:0000244|PDB:1SC3}. FT HELIX 348 360 {ECO:0000244|PDB:1SC3}. FT TURN 361 363 {ECO:0000244|PDB:1SC3}. FT HELIX 366 376 {ECO:0000244|PDB:1SC3}. FT STRAND 381 383 {ECO:0000244|PDB:6F6R}. FT STRAND 388 391 {ECO:0000244|PDB:1SC3}. FT STRAND 395 397 {ECO:0000244|PDB:1RWM}. SQ SEQUENCE 404 AA; 45159 MW; ABF33CF33CC71584 CRC64; MADKVLKEKR KLFIRSMGEG TINGLLDELL QTRVLNKEEM EKVKRENATV MDKTRALIDS VIPKGAQACQ ICITYICEED SYLAGTLGLS ADQTSGNYLN MQDSQGVLSS FPAPQAVQDN PAMPTSSGSE GNVKLCSLEE AQRIWKQKSA EIYPIMDKSS RTRLALIICN EEFDSIPRRT GAEVDITGMT MLLQNLGYSV DVKKNLTASD MTTELEAFAH RPEHKTSDST FLVFMSHGIR EGICGKKHSE QVPDILQLNA IFNMLNTKNC PSLKDKPKVI IIQACRGDSP GVVWFKDSVG VSGNLSLPTT EEFEDDAIKK AHIEKDFIAF CSSTPDNVSW RHPTMGSVFI GRLIEHMQEY ACSCDVEEIF RKVRFSFEQP DGRAQMPTTE RVTLTRCFYL FPGH // ID CASP9_HUMAN Reviewed; 416 AA. AC P55211; B4E1A3; O95348; Q53Y70; Q5JRU9; Q5UGI1; Q92852; Q9BQ62; AC Q9UEQ3; Q9UIJ8; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 22-FEB-2003, sequence version 3. DT 18-JUL-2018, entry version 207. DE RecName: Full=Caspase-9; DE Short=CASP-9; DE EC=3.4.22.62 {ECO:0000269|PubMed:23516580}; DE AltName: Full=Apoptotic protease Mch-6; DE AltName: Full=Apoptotic protease-activating factor 3; DE Short=APAF-3; DE AltName: Full=ICE-like apoptotic protease 6; DE Short=ICE-LAP6; DE Contains: DE RecName: Full=Caspase-9 subunit p35; DE Contains: DE RecName: Full=Caspase-9 subunit p10; DE Flags: Precursor; GN Name=CASP9; Synonyms=MCH6; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS VAL-28 AND RP ARG-221. RX PubMed=8663294; DOI=10.1074/jbc.271.28.16720; RA Duan H., Orth K., Chinnaiyan A.M., Poirier G.G., Froelich C.J., RA He W.-W., Dixit V.M.; RT "ICE-LAP6, a novel member of the ICE/Ced-3 gene family, is activated RT by the cytotoxic T cell protease granzyme B."; RL J. Biol. Chem. 271:16720-16724(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PROTEOLYTIC PROCESSING. RC TISSUE=T-cell; RX PubMed=8900201; DOI=10.1074/jbc.271.43.27099; RA Srinivasula S.M., Fernandes-Alnemri T., Zangrilli J., Robertson N., RA Armstrong R.C., Wang L., Trapani J.A., Tomaselli K.J., Litwack G., RA Alnemri E.S.; RT "The Ced-3/interleukin 1beta converting enzyme-like homolog Mch6 and RT the lamin-cleaving enzyme Mch2alpha are substrates for the apoptotic RT mediator CPP32."; RL J. Biol. Chem. 271:27099-27106(1996). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10384055; DOI=10.1007/s003359901086; RA Hadano S., Nasir J., Nichol K., Rasper D.M., Vaillancourt J.P., RA Sherer S.W., Beatty B.G., Ikeda J.E., Nicholson D.W., Hayden M.R.; RT "Genomic organization of the human caspase-9 gene on chromosome RT 1p36.1-p36.3."; RL Mamm. Genome 10:757-760(1999). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=10070954; RA Srinivasula S.M., Ahmad M., Guo Y., Zhan Y., Lazebnik Y., RA Fernandes-Alnemri T., Alnemri E.S.; RT "Identification of an endogenous dominant-negative short isoform of RT caspase-9 that can regulate apoptosis."; RL Cancer Res. 59:999-1002(1999). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Stomach cancer; RA Izawa M., Mori T., Ito H., Sairenji T.; RT "Molecular cloning and sequencing of a cDNA predicting an alternative RT form of pro-caspase-9 from human gastric cancer cell lines."; RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Miho Y., Momoi T., Fujita E.; RT "A novel splicing product of human caspase-9 lacking protease RT activity."; RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT VAL-28. RX PubMed=9890966; DOI=10.1074/jbc.274.4.2072; RA Seol D.W., Billiar T.R.; RT "A caspase-9 variant missing the catalytic site is an endogenous RT inhibitor of apoptosis."; RL J. Biol. Chem. 274:2072-2076(1999). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND VARIANT VAL-28. RX PubMed=16780893; DOI=10.1016/j.lfs.2006.04.026; RA Wang P., Shi T., Ma D.; RT "Cloning of a novel human caspase-9 splice variant containing only the RT CARD domain."; RL Life Sci. 79:934-940(2006). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-28; LEU-99; RP ILE-102; VAL-106; ASP-114; HIS-173 AND ARG-221. RG NIEHS SNPs program; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Kidney; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [13] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [14] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Eye, and Lymph; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [15] RP PHOSPHORYLATION AT THR-125. RX PubMed=12792650; DOI=10.1038/ncb1005; RA Allan L.A., Morrice N., Brady S., Magee G., Pathak S., Clarke P.R.; RT "Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK RT MAPK."; RL Nat. Cell Biol. 5:647-654(2003). RN [16] RP INTERACTION WITH BIRC6/BRUCE. RX PubMed=15200957; DOI=10.1016/j.molcel.2004.05.018; RA Bartke T., Pohl C., Pyrowolakis G., Jentsch S.; RT "Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 RT ubiquitin ligase."; RL Mol. Cell 14:801-811(2004). RN [17] RP FUNCTION IN APOPTOSIS, INTERACTION WITH ABL1, PROTEOLYTIC PROCESSING, RP PHOSPHORYLATION AT TYR-153 BY ABL1, AND MUTAGENESIS OF TYR-153. RX PubMed=15657060; DOI=10.1074/jbc.M413787200; RA Raina D., Pandey P., Ahmad R., Bharti A., Ren J., Kharbanda S., RA Weichselbaum R., Kufe D.; RT "c-Abl tyrosine kinase regulates caspase-9 autocleavage in the RT apoptotic response to DNA damage."; RL J. Biol. Chem. 280:11147-11151(2005). RN [18] RP INTERACTION WITH HAX1, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=16857965; DOI=10.1161/01.RES.0000237387.05259.a5; RA Han Y., Chen Y.S., Liu Z., Bodyak N., Rigor D., Bisping E., Pu W.T., RA Kang P.M.; RT "Overexpression of HAX-1 protects cardiac myocytes from apoptosis RT through caspase-9 inhibition."; RL Circ. Res. 99:415-423(2006). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-125; SER-302 AND RP SER-307, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [20] RP INTERACTION WITH EFHD2. RX PubMed=19118655; DOI=10.1016/j.jprot.2008.11.016; RA Checinska A., Giaccone G., Rodriguez J.A., Kruyt F.A.E., Jimenez C.R.; RT "Comparative proteomics analysis of caspase-9-protein complexes in RT untreated and cytochrome c/dATP stimulated lysates of NSCLC cells."; RL J. Proteomics 72:575-585(2009). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-307, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-310, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [23] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 140-416, AND SUBUNIT. RX PubMed=11734640; DOI=10.1073/pnas.231465798; RA Renatus M., Stennicke H.R., Scott F.L., Liddington R.C., RA Salvesen G.S.; RT "Dimer formation drives the activation of the cell death protease RT caspase 9."; RL Proc. Natl. Acad. Sci. U.S.A. 98:14250-14255(2001). RN [24] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 140-416 IN COMPLEX WITH RP BIRC4/XIAP. RX PubMed=12620238; DOI=10.1016/S1097-2765(03)00054-6; RA Shiozaki E.N., Chai J., Rigotti D.J., Riedl S.J., Li P., RA Srinivasula S.M., Alnemri E.S., Fairman R., Shi Y.; RT "Mechanism of XIAP-mediated inhibition of caspase-9."; RL Mol. Cell 11:519-527(2003). RN [25] RP X-RAY CRYSTALLOGRAPHY (3.49 ANGSTROMS) OF 140-416 IN COMPLEX WITH RP E.COLI NLEF, INTERACTION WITH E.COLI NLEF, SUBUNIT, CATALYTIC RP ACTIVITY, FUNCTION, AND ENZYME REGULATION. RX PubMed=23516580; DOI=10.1371/journal.pone.0058937; RA Blasche S., Mortl M., Steuber H., Siszler G., Nisa S., Schwarz F., RA Lavrik I., Gronewold T.M., Maskos K., Donnenberg M.S., Ullmann D., RA Uetz P., Kogl M.; RT "The E. coli effector protein NleF is a caspase inhibitor."; RL PLoS ONE 8:E58937-E58937(2013). CC -!- FUNCTION: Involved in the activation cascade of caspases CC responsible for apoptosis execution. Binding of caspase-9 to Apaf- CC 1 leads to activation of the protease which then cleaves and CC activates caspase-3. Promotes DNA damage-induced apoptosis in a CC ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP- CC ribose) polymerase (PARP). CC -!- FUNCTION: Isoform 2 lacks activity is an dominant-negative CC inhibitor of caspase-9. CC -!- CATALYTIC ACTIVITY: Strict requirement for an Asp residue at CC position P1 and with a marked preference for His at position P2. CC It has a preferred cleavage sequence of Leu-Gly-His-Asp-|-Xaa. CC {ECO:0000269|PubMed:23516580}. CC -!- ENZYME REGULATION: Inhibited by the effector protein NleF that is CC produced by pathogenic E.coli; this inhibits apoptosis. CC {ECO:0000269|PubMed:23516580}. CC -!- SUBUNIT: Heterotetramer that consists of two anti-parallel CC arranged heterodimers, each one formed by a 35 kDa (p35) and a 10 CC kDa (p10) subunit. Caspase-9 and APAF1 bind to each other via CC their respective NH2-terminal CED-3 homologous domains in the CC presence of cytochrome C and ATP. Interacts (inactive form) with CC EFHD2. Interacts with HAX1. Interacts with BIRC2/c-IAP1, CC XIAP/BIRC4, BIRC5/survivin, BIRC6/bruce and BIRC7/livin. Interacts CC with ABL1 (via SH3 domain); the interaction is direct and CC increases in the response of cells to genotoxic stress and ABL1/c- CC Abl activation. Interacts with NleF from pathogenic E.coli. CC {ECO:0000269|PubMed:11734640, ECO:0000269|PubMed:12620238, CC ECO:0000269|PubMed:15200957, ECO:0000269|PubMed:15657060, CC ECO:0000269|PubMed:16857965, ECO:0000269|PubMed:19118655, CC ECO:0000269|PubMed:23516580}. CC -!- INTERACTION: CC O14727:APAF1; NbExp=25; IntAct=EBI-516799, EBI-446492; CC Q13490:BIRC2; NbExp=9; IntAct=EBI-516799, EBI-514538; CC Q13489:BIRC3; NbExp=2; IntAct=EBI-516799, EBI-517709; CC O15392:BIRC5; NbExp=2; IntAct=EBI-516799, EBI-518823; CC Q96CA5:BIRC7; NbExp=10; IntAct=EBI-516799, EBI-517623; CC Q6PIA0:BIRC8; NbExp=3; IntAct=EBI-516799, EBI-2129837; CC P42574:CASP3; NbExp=3; IntAct=EBI-516799, EBI-524064; CC P43146:DCC; NbExp=2; IntAct=EBI-516799, EBI-1222919; CC Q13418:ILK; NbExp=2; IntAct=EBI-516799, EBI-747644; CC P98170:XIAP; NbExp=15; IntAct=EBI-516799, EBI-517127; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=9L, Alpha; CC IsoId=P55211-1; Sequence=Displayed; CC Name=2; Synonyms=9S, Beta; CC IsoId=P55211-2; Sequence=VSP_000818; CC Name=3; Synonyms=Gamma; CC IsoId=P55211-3; Sequence=VSP_043910, VSP_043911; CC Note=May function as an endogenous apoptotic inhibitor, inhibits CC the BAX-mediated cleavage of procaspase-3.; CC Name=4; CC IsoId=P55211-4; Sequence=VSP_044256; CC -!- TISSUE SPECIFICITY: Ubiquitous, with highest expression in the CC heart, moderate expression in liver, skeletal muscle, and CC pancreas. Low levels in all other tissues. Within the heart, CC specifically expressed in myocytes. {ECO:0000269|PubMed:16857965}. CC -!- DEVELOPMENTAL STAGE: Expressed at low levels in fetal heart, at CC moderate levels in neonate heart, and at high levels in adult CC heart. {ECO:0000269|PubMed:16857965}. CC -!- PTM: Cleavages at Asp-315 by granzyme B and at Asp-330 by caspase- CC 3 generate the two active subunits. Caspase-8 and -10 can also be CC involved in these processing events. CC -!- PTM: Phosphorylated at Thr-125 by MAPK1/ERK2. Phosphorylation at CC Thr-125 is sufficient to block caspase-9 processing and subsequent CC caspase-3 activation. Phosphorylation on Tyr-153 by ABL1/c-Abl; CC occurs in the response of cells to DNA damage. CC {ECO:0000269|PubMed:12792650, ECO:0000269|PubMed:15657060}. CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/CASP9ID423ch1p36.html"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/casp9/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Caspase-9 entry; CC URL="https://en.wikipedia.org/wiki/Caspase-9"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; U56390; AAC50640.1; -; mRNA. DR EMBL; U60521; AAC50776.1; -; mRNA. DR EMBL; AB019205; BAA82697.1; -; Genomic_DNA. DR EMBL; AF093130; AAD12248.1; -; mRNA. DR EMBL; AB015653; BAA78780.1; -; mRNA. DR EMBL; AB020979; BAA87905.1; -; mRNA. DR EMBL; AF110376; AAD13615.1; -; mRNA. DR EMBL; AY732490; AAV33129.1; -; mRNA. DR EMBL; AY214168; AAO21133.1; -; Genomic_DNA. DR EMBL; BT006911; AAP35557.1; -; mRNA. DR EMBL; AK303743; BAG64715.1; -; mRNA. DR EMBL; AL512883; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471167; EAW51730.1; -; Genomic_DNA. DR EMBL; CH471167; EAW51731.1; -; Genomic_DNA. DR EMBL; BC002452; AAH02452.1; -; mRNA. DR EMBL; BC006463; AAH06463.1; -; mRNA. DR CCDS; CCDS158.1; -. [P55211-1] DR CCDS; CCDS159.2; -. [P55211-4] DR CCDS; CCDS59995.1; -. [P55211-2] DR PIR; G02635; G02635. DR RefSeq; NP_001220.2; NM_001229.4. [P55211-1] DR RefSeq; NP_001264983.1; NM_001278054.1. [P55211-2] DR RefSeq; NP_127463.2; NM_032996.3. [P55211-4] DR RefSeq; XP_005246071.1; XM_005246014.2. [P55211-4] DR UniGene; Hs.329502; -. DR PDB; 1JXQ; X-ray; 2.80 A; A/B/C/D=140-416. DR PDB; 1NW9; X-ray; 2.40 A; B=140-416. DR PDB; 2AR9; X-ray; 2.80 A; A/B/C/D=139-416. DR PDB; 3D9T; X-ray; 1.50 A; C/D=316-321. DR PDB; 3V3K; X-ray; 3.49 A; A/C/E/G/I/K/M/O=141-416. DR PDB; 3YGS; X-ray; 2.50 A; P=1-95. DR PDB; 4RHW; X-ray; 2.10 A; E/F=1-100. DR PDB; 5JUY; EM; 4.10 A; O/P/Q/R=1-95. DR PDB; 5WVC; X-ray; 2.99 A; B/D/F=1-128. DR PDB; 5WVE; EM; 4.40 A; S/T/U/V/Y=1-100. DR PDBsum; 1JXQ; -. DR PDBsum; 1NW9; -. DR PDBsum; 2AR9; -. DR PDBsum; 3D9T; -. DR PDBsum; 3V3K; -. DR PDBsum; 3YGS; -. DR PDBsum; 4RHW; -. DR PDBsum; 5JUY; -. DR PDBsum; 5WVC; -. DR PDBsum; 5WVE; -. DR ProteinModelPortal; P55211; -. DR SMR; P55211; -. DR BioGrid; 107292; 34. DR CORUM; P55211; -. DR DIP; DIP-27625N; -. DR ELM; P55211; -. DR IntAct; P55211; 20. DR MINT; P55211; -. DR STRING; 9606.ENSP00000330237; -. DR BindingDB; P55211; -. DR ChEMBL; CHEMBL2273; -. DR GuidetoPHARMACOLOGY; 1625; -. DR MEROPS; C14.010; -. DR iPTMnet; P55211; -. DR PhosphoSitePlus; P55211; -. DR DMDM; 28558771; -. DR EPD; P55211; -. DR MaxQB; P55211; -. DR PaxDb; P55211; -. DR PeptideAtlas; P55211; -. DR PRIDE; P55211; -. DR ProteomicsDB; 56814; -. DR ProteomicsDB; 56815; -. [P55211-2] DR ProteomicsDB; 56816; -. [P55211-3] DR DNASU; 842; -. DR Ensembl; ENST00000333868; ENSP00000330237; ENSG00000132906. [P55211-1] DR Ensembl; ENST00000348549; ENSP00000255256; ENSG00000132906. [P55211-2] DR Ensembl; ENST00000375890; ENSP00000365051; ENSG00000132906. [P55211-4] DR GeneID; 842; -. DR KEGG; hsa:842; -. DR UCSC; uc001awn.5; human. [P55211-1] DR CTD; 842; -. DR DisGeNET; 842; -. DR EuPathDB; HostDB:ENSG00000132906.17; -. DR GeneCards; CASP9; -. DR HGNC; HGNC:1511; CASP9. DR HPA; CAB004348; -. DR HPA; HPA001473; -. DR HPA; HPA046488; -. DR MIM; 602234; gene. DR neXtProt; NX_P55211; -. DR OpenTargets; ENSG00000132906; -. DR PharmGKB; PA26094; -. DR eggNOG; KOG3573; Eukaryota. DR eggNOG; ENOG410ZQIE; LUCA. DR GeneTree; ENSGT00760000118912; -. DR HOVERGEN; HBG059022; -. DR InParanoid; P55211; -. DR KO; K04399; -. DR PhylomeDB; P55211; -. DR TreeFam; TF102023; -. DR BRENDA; 3.4.22.62; 2681. DR Reactome; R-HSA-111458; Formation of apoptosome. DR Reactome; R-HSA-111459; Activation of caspases through apoptosome-mediated cleavage. DR Reactome; R-HSA-111463; SMAC binds to IAPs. DR Reactome; R-HSA-111464; SMAC-mediated dissociation of IAP:caspase complexes. DR Reactome; R-HSA-168638; NOD1/2 Signaling Pathway. DR Reactome; R-HSA-198323; AKT phosphorylates targets in the cytosol. DR Reactome; R-HSA-418889; Ligand-independent caspase activation via DCC. DR Reactome; R-HSA-5674400; Constitutive Signaling by AKT1 E17K in Cancer. DR SABIO-RK; P55211; -. DR SIGNOR; P55211; -. DR EvolutionaryTrace; P55211; -. DR GeneWiki; Caspase-9; -. DR GenomeRNAi; 842; -. DR PMAP-CutDB; P55211; -. DR PRO; PR:P55211; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; ENSG00000132906; -. DR CleanEx; HS_CASP9; -. DR ExpressionAtlas; P55211; baseline and differential. DR Genevisible; P55211; HS. DR GO; GO:0043293; C:apoptosome; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; IEA:Ensembl. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:UniProtKB. DR GO; GO:0097200; F:cysteine-type endopeptidase activity involved in execution phase of apoptosis; IBA:GO_Central. DR GO; GO:0008047; F:enzyme activator activity; TAS:ProtInc. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0008233; F:peptidase activity; IDA:BHF-UCL. DR GO; GO:0019901; F:protein kinase binding; IDA:UniProtKB. DR GO; GO:0017124; F:SH3 domain binding; IDA:UniProtKB. DR GO; GO:0008635; P:activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c; TAS:ProtInc. DR GO; GO:0007568; P:aging; IEA:Ensembl. DR GO; GO:0006915; P:apoptotic process; IMP:UniProtKB. DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl. DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB. DR GO; GO:0034644; P:cellular response to UV; IDA:UniProtKB. DR GO; GO:0097194; P:execution phase of apoptosis; IBA:GO_Central. DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; TAS:Reactome. DR GO; GO:0034349; P:glial cell apoptotic process; IEA:Ensembl. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IMP:UniProtKB. DR GO; GO:0030220; P:platelet formation; TAS:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:2001020; P:regulation of response to DNA damage stimulus; IMP:UniProtKB. DR GO; GO:0046677; P:response to antibiotic; IEA:Ensembl. DR GO; GO:0032025; P:response to cobalt ion; IEA:Ensembl. DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl. DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0042770; P:signal transduction in response to DNA damage; IDA:UniProtKB. DR CDD; cd00032; CASc; 1. DR InterPro; IPR001315; CARD. DR InterPro; IPR033171; Caspase-9. DR InterPro; IPR029030; Caspase-like_dom_sf. DR InterPro; IPR033139; Caspase_cys_AS. DR InterPro; IPR016129; Caspase_his_AS. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR002138; Pept_C14_p10. DR InterPro; IPR001309; Pept_C14_p20. DR InterPro; IPR015917; Pept_C14A. DR PANTHER; PTHR10454:SF157; PTHR10454:SF157; 2. DR Pfam; PF00619; CARD; 1. DR PRINTS; PR00376; IL1BCENZYME. DR SMART; SM00114; CARD; 1. DR SMART; SM00115; CASc; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR SUPFAM; SSF52129; SSF52129; 1. DR PROSITE; PS50209; CARD; 1. DR PROSITE; PS01122; CASPASE_CYS; 1. DR PROSITE; PS01121; CASPASE_HIS; 1. DR PROSITE; PS50207; CASPASE_P10; 1. DR PROSITE; PS50208; CASPASE_P20; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; Complete proteome; KW Hydrolase; Phosphoprotein; Polymorphism; Protease; Reference proteome; KW Thiol protease; Zymogen. FT PROPEP 1 ? {ECO:0000255}. FT /FTId=PRO_0000004640. FT CHAIN ? 315 Caspase-9 subunit p35. FT /FTId=PRO_0000004641. FT PROPEP 316 330 FT /FTId=PRO_0000004642. FT CHAIN 331 416 Caspase-9 subunit p10. FT /FTId=PRO_0000004643. FT DOMAIN 1 92 CARD. {ECO:0000255|PROSITE- FT ProRule:PRU00046}. FT ACT_SITE 237 237 {ECO:0000250}. FT ACT_SITE 287 287 {ECO:0000250}. FT MOD_RES 125 125 Phosphothreonine; by MAPK1. FT {ECO:0000244|PubMed:18669648, FT ECO:0000269|PubMed:12792650}. FT MOD_RES 153 153 Phosphotyrosine; by ABL1. FT {ECO:0000269|PubMed:15657060}. FT MOD_RES 302 302 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 307 307 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:20068231}. FT MOD_RES 310 310 Phosphoserine. FT {ECO:0000244|PubMed:23186163}. FT VAR_SEQ 1 83 Missing (in isoform 4). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_044256. FT VAR_SEQ 140 289 Missing (in isoform 2). FT {ECO:0000303|PubMed:10070954, FT ECO:0000303|PubMed:9890966, FT ECO:0000303|Ref.5, ECO:0000303|Ref.6}. FT /FTId=VSP_000818. FT VAR_SEQ 152 154 AYI -> TVL (in isoform 3). FT {ECO:0000303|PubMed:16780893}. FT /FTId=VSP_043910. FT VAR_SEQ 155 416 Missing (in isoform 3). FT {ECO:0000303|PubMed:16780893}. FT /FTId=VSP_043911. FT VARIANT 28 28 A -> V (in dbSNP:rs1052571). FT {ECO:0000269|PubMed:16780893, FT ECO:0000269|PubMed:8663294, FT ECO:0000269|PubMed:9890966, FT ECO:0000269|Ref.9}. FT /FTId=VAR_015415. FT VARIANT 99 99 S -> L (in dbSNP:rs4646008). FT {ECO:0000269|Ref.9}. FT /FTId=VAR_015416. FT VARIANT 102 102 T -> I (in dbSNP:rs2308941). FT {ECO:0000269|Ref.9}. FT /FTId=VAR_015417. FT VARIANT 106 106 L -> V (in dbSNP:rs2308938). FT {ECO:0000269|Ref.9}. FT /FTId=VAR_015418. FT VARIANT 114 114 E -> D (in dbSNP:rs2020897). FT {ECO:0000269|Ref.9}. FT /FTId=VAR_015419. FT VARIANT 136 136 F -> L (in dbSNP:rs1132312). FT /FTId=VAR_059198. FT VARIANT 173 173 R -> H (in dbSNP:rs2308950). FT {ECO:0000269|Ref.9}. FT /FTId=VAR_015420. FT VARIANT 176 176 G -> R (in dbSNP:rs2308949). FT /FTId=VAR_016131. FT VARIANT 185 185 I -> M (in dbSNP:rs9282624). FT /FTId=VAR_022053. FT VARIANT 192 192 R -> C (in dbSNP:rs2308939). FT /FTId=VAR_016132. FT VARIANT 221 221 Q -> R (in dbSNP:rs1052576). FT {ECO:0000269|PubMed:8663294, FT ECO:0000269|Ref.9}. FT /FTId=VAR_015421. FT MUTAGEN 153 153 Y->F: Inhibits tyrosine phosphorylation. FT Reduces caspase-9 subunit p35 formation FT in response to genotoxic stress. FT Attenuates ABL1/c-Abl-mediated caspase-3 FT activation, DNA fragmentation and UV FT irradiation-induced apoptosis. FT {ECO:0000269|PubMed:15657060}. FT CONFLICT 32 32 R -> S (in Ref. 2; AAC50776, 3; BAA82697 FT and 6; BAA87905). {ECO:0000305}. FT CONFLICT 96 96 A -> G (in Ref. 1; AAC50640). FT {ECO:0000305}. FT CONFLICT 197 197 L -> P (in Ref. 2; AAC50776 and 3; FT BAA82697). {ECO:0000305}. FT HELIX 3 11 {ECO:0000244|PDB:4RHW}. FT HELIX 13 19 {ECO:0000244|PDB:4RHW}. FT TURN 23 25 {ECO:0000244|PDB:4RHW}. FT HELIX 26 31 {ECO:0000244|PDB:4RHW}. FT HELIX 37 44 {ECO:0000244|PDB:4RHW}. FT HELIX 51 62 {ECO:0000244|PDB:4RHW}. FT HELIX 69 79 {ECO:0000244|PDB:4RHW}. FT HELIX 83 93 {ECO:0000244|PDB:4RHW}. FT HELIX 143 147 {ECO:0000244|PDB:1NW9}. FT TURN 149 151 {ECO:0000244|PDB:1NW9}. FT STRAND 157 159 {ECO:0000244|PDB:1JXQ}. FT STRAND 161 167 {ECO:0000244|PDB:1NW9}. FT HELIX 173 175 {ECO:0000244|PDB:1NW9}. FT HELIX 183 196 {ECO:0000244|PDB:1NW9}. FT STRAND 199 206 {ECO:0000244|PDB:1NW9}. FT HELIX 209 221 {ECO:0000244|PDB:1NW9}. FT HELIX 224 226 {ECO:0000244|PDB:2AR9}. FT STRAND 228 239 {ECO:0000244|PDB:1NW9}. FT STRAND 244 246 {ECO:0000244|PDB:1NW9}. FT STRAND 249 251 {ECO:0000244|PDB:1NW9}. FT STRAND 257 259 {ECO:0000244|PDB:1NW9}. FT HELIX 260 265 {ECO:0000244|PDB:1NW9}. FT TURN 269 271 {ECO:0000244|PDB:1NW9}. FT HELIX 273 275 {ECO:0000244|PDB:1NW9}. FT STRAND 280 287 {ECO:0000244|PDB:1NW9}. FT STRAND 317 319 {ECO:0000244|PDB:3D9T}. FT STRAND 340 346 {ECO:0000244|PDB:1NW9}. FT STRAND 351 353 {ECO:0000244|PDB:1NW9}. FT STRAND 354 356 {ECO:0000244|PDB:3V3K}. FT TURN 357 359 {ECO:0000244|PDB:1JXQ}. FT HELIX 362 374 {ECO:0000244|PDB:1NW9}. FT TURN 375 377 {ECO:0000244|PDB:1NW9}. FT HELIX 380 392 {ECO:0000244|PDB:1NW9}. FT STRAND 395 398 {ECO:0000244|PDB:1JXQ}. FT STRAND 402 406 {ECO:0000244|PDB:1JXQ}. FT STRAND 408 410 {ECO:0000244|PDB:1NW9}. SQ SEQUENCE 416 AA; 46281 MW; 78E0180DF2A3BDD2 CRC64; MDEADRRLLR RCRLRLVEEL QVDQLWDALL SRELFRPHMI EDIQRAGSGS RRDQARQLII DLETRGSQAL PLFISCLEDT GQDMLASFLR TNRQAAKLSK PTLENLTPVV LRPEIRKPEV LRPETPRPVD IGSGGFGDVG ALESLRGNAD LAYILSMEPC GHCLIINNVN FCRESGLRTR TGSNIDCEKL RRRFSSLHFM VEVKGDLTAK KMVLALLELA QQDHGALDCC VVVILSHGCQ ASHLQFPGAV YGTDGCPVSV EKIVNIFNGT SCPSLGGKPK LFFIQACGGE QKDHGFEVAS TSPEDESPGS NPEPDATPFQ EGLRTFDQLD AISSLPTPSD IFVSYSTFPG FVSWRDPKSG SWYVETLDDI FEQWAHSEDL QSLLLRVANA VSVKGIYKQM PGCFNFLRKK LFFKTS // ID CED4_CAEEL Reviewed; 571 AA. AC P30429; Q5BHI5; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 29-MAR-2005, sequence version 2. DT 20-JUN-2018, entry version 153. DE RecName: Full=Cell death protein 4; GN Name=ced-4; ORFNames=C35D10.9; OS Caenorhabditis elegans. OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; OC Rhabditoidea; Rhabditidae; Peloderinae; Caenorhabditis. OX NCBI_TaxID=6239; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A), FUNCTION, DEVELOPMENTAL RP STAGE, AND DISRUPTION PHENOTYPE. RX PubMed=1286611; RA Yuan J., Horvitz H.R.; RT "The Caenorhabditis elegans cell death gene ced-4 encodes a novel RT protein and is expressed during the period of extensive programmed RT cell death."; RL Development 116:309-320(1992). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Bristol N2; RX PubMed=9851916; DOI=10.1126/science.282.5396.2012; RG The C. elegans sequencing consortium; RT "Genome sequence of the nematode C. elegans: a platform for RT investigating biology."; RL Science 282:2012-2018(1998). RN [3] RP FUNCTION. RX PubMed=3955651; RA Ellis H.M., Horvitz H.R.; RT "Genetic control of programmed cell death in the nematode C. RT elegans."; RL Cell 44:817-829(1986). RN [4] RP FUNCTION, AND ALTERNATIVE SPLICING. RX PubMed=8706125; DOI=10.1016/S0092-8674(00)80092-6; RA Shaham S., Horvitz H.R.; RT "An alternatively spliced C. elegans ced-4 RNA encodes a novel cell RT death inhibitor."; RL Cell 86:201-208(1996). RN [5] RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND INTERACTION WITH CED-9. RX PubMed=9027313; DOI=10.1126/science.275.5303.1126; RA Wu D., Wallen H.D., Nunez G.; RT "Interaction and regulation of subcellular localization of CED-4 by RT CED-9."; RL Science 275:1126-1129(1997). RN [6] RP FUNCTION. RX PubMed=9927601; RA Gumienny T.L., Lambie E., Hartwieg E., Horvitz H.R., Hengartner M.O.; RT "Genetic control of programmed cell death in the Caenorhabditis RT elegans hermaphrodite germline."; RL Development 126:1011-1022(1999). RN [7] RP INTERACTION WITH MAC-1, AND MUTAGENESIS OF ILE-280. RX PubMed=10101135; RA Wu D., Chen P.J., Chen S., Hu Y., Nunez G., Ellis R.E.; RT "C. elegans MAC-1, an essential member of the AAA family of ATPases, RT can bind CED-4 and prevent cell death."; RL Development 126:2021-2031(1999). RN [8] RP FUNCTION, AND INTERACTION WITH FEM-1. RX PubMed=10764728; DOI=10.1074/jbc.C000146200; RA Chan S.L., Yee K.S., Tan K.M., Yu V.C.; RT "The Caenorhabditis elegans sex determination protein FEM-1 is a CED-3 RT substrate that associates with CED-4 and mediates apoptosis in RT mammalian cells."; RL J. Biol. Chem. 275:17925-17928(2000). RN [9] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=10688797; DOI=10.1126/science.287.5457.1485; RA Chen F., Hersh B.M., Conradt B., Zhou Z., Riemer D., Gruenbaum Y., RA Horvitz H.R.; RT "Translocation of C. elegans CED-4 to nuclear membranes during RT programmed cell death."; RL Science 287:1485-1489(2000). RN [10] RP FUNCTION. RX PubMed=11226309; DOI=10.1073/pnas.041613098; RA Aballay A., Ausubel F.M.; RT "Programmed cell death mediated by ced-3 and ced-4 protects RT Caenorhabditis elegans from Salmonella typhimurium-mediated killing."; RL Proc. Natl. Acad. Sci. U.S.A. 98:2735-2739(2001). RN [11] RP FUNCTION, AND INTERACTION WITH CED-9. RX PubMed=15383288; DOI=10.1016/j.molcel.2004.08.022; RA Yan N., Gu L., Kokel D., Chai J., Li W., Han A., Chen L., Xue D., RA Shi Y.; RT "Structural, biochemical, and functional analyses of CED-9 recognition RT by the proapoptotic proteins EGL-1 and CED-4."; RL Mol. Cell 15:999-1006(2004). RN [12] RP FUNCTION. RX PubMed=17329362; DOI=10.1242/dev.02818; RA Maurer C.W., Chiorazzi M., Shaham S.; RT "Timing of the onset of a developmental cell death is controlled by RT transcriptional induction of the C. elegans ced-3 caspase-encoding RT gene."; RL Development 134:1357-1368(2007). RN [13] RP FUNCTION. RX PubMed=21901106; DOI=10.1371/journal.pgen.1002238; RA Rutkowski R., Dickinson R., Stewart G., Craig A., Schimpl M., RA Keyse S.M., Gartner A.; RT "Regulation of Caenorhabditis elegans p53/CEP-1-dependent germ cell RT apoptosis by Ras/MAPK signaling."; RL PLoS Genet. 7:E1002238-E1002238(2011). RN [14] RP FUNCTION. RX PubMed=22629231; DOI=10.1371/journal.pbio.1001331; RA Pinan-Lucarre B., Gabel C.V., Reina C.P., Hulme S.E., RA Shevkoplyas S.S., Slone R.D., Xue J., Qiao Y., Weisberg S., RA Roodhouse K., Sun L., Whitesides G.M., Samuel A., Driscoll M.; RT "The core apoptotic executioner proteins CED-3 and CED-4 promote RT initiation of neuronal regeneration in Caenorhabditis elegans."; RL PLoS Biol. 10:E1001331-E1001331(2012). RN [15] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=23106139; DOI=10.1111/jnc.12072; RA VanDuyn N., Settivari R., LeVora J., Zhou S., Unrine J., Nass R.; RT "The metal transporter SMF-3/DMT-1 mediates aluminum-induced dopamine RT neuron degeneration."; RL J. Neurochem. 124:147-157(2013). RN [16] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=25432023; DOI=10.7554/eLife.04265; RA Weaver B.P., Zabinsky R., Weaver Y.M., Lee E.S., Xue D., Han M.; RT "CED-3 caspase acts with miRNAs to regulate non-apoptotic gene RT expression dynamics for robust development in C. elegans."; RL Elife 3:E04265-E04265(2014). RN [17] RP FUNCTION. RX PubMed=26074078; DOI=10.1016/j.celrep.2015.05.031; RA Meng L., Mulcahy B., Cook S.J., Neubauer M., Wan A., Jin Y., Yan D.; RT "The cell death pathway regulates synapse elimination through cleavage RT of gelsolin in Caenorhabditis elegans neurons."; RL Cell Rep. 11:1737-1748(2015). RN [18] RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF ISOFORM A IN COMPLEX WITH RP ATP; MAGNESIUM AND CED-9, FUNCTION, AND MUTAGENESIS OF VAL-252; RP ARG-255; MET-256 AND 272-ASP-ASP-273. RX PubMed=16208361; DOI=10.1038/nature04002; RA Yan N., Chai J., Lee E.S., Gu L., Liu Q., He J., Wu J.W., Kokel D., RA Li H., Hao Q., Xue D., Shi Y.; RT "Structure of the CED-4-CED-9 complex provides insights into RT programmed cell death in Caenorhabditis elegans."; RL Nature 437:831-837(2005). RN [19] RP X-RAY CRYSTALLOGRAPHY (3.53 ANGSTROMS) IN COMPLEX WITH CED-3; RP MAGNESIUM AND ATP, AND FUNCTION. RX PubMed=20434985; DOI=10.1016/j.cell.2010.03.017; RA Qi S., Pang Y., Hu Q., Liu Q., Li H., Zhou Y., He T., Liang Q., RA Liu Y., Yuan X., Luo G., Li H., Wang J., Yan N., Shi Y.; RT "Crystal structure of the Caenorhabditis elegans apoptosome reveals an RT octameric assembly of CED-4."; RL Cell 141:446-457(2010). RN [20] RP X-RAY CRYSTALLOGRAPHY (3.21 ANGSTROMS) IN COMPLEX WITH CED-3 AND ATP RP (ISOFORM A), FUNCTION, AND MUTAGENESIS OF ALA-416. RX PubMed=24065769; DOI=10.1101/gad.224428.113; RA Huang W., Jiang T., Choi W., Qi S., Pang Y., Hu Q., Xu Y., Gong X., RA Jeffrey P.D., Wang J., Shi Y.; RT "Mechanistic insights into CED-4-mediated activation of CED-3."; RL Genes Dev. 27:2039-2048(2013). CC -!- FUNCTION: Component of the egl-1, ced-9, ced-4 and ced-3 apoptotic CC signaling cascade required for the initiation of programmed cell CC death in cells fated to die during embryonic and postembryonic CC development (PubMed:3955651). During oogenesis, required for CC germline apoptosis downstream of ced-9 and upstream of ced-3 but CC independently of egl-1 (PubMed:9927601). May regulate germline CC apoptosis in response to DNA damage, probably downstream of let- CC 60/ras and mpk-1 pathway (PubMed:21901106). Regulates CEP neuron CC apoptosis in response to high Al(3+) levels (PubMed:23106139). CC During male tail morphogenesis, promotes apoptosis of the tail- CC spike cell upstream of ced-3 but independently of egl-1 and ced-9 CC (PubMed:17329362). May play a role in sex-specific cell apoptosis, CC probably by promoting ced-3-mediated cleavage of sex-determining CC protein fem-1 (PubMed:10764728). During larval development, CC required for the elimination of transient presynaptic components CC downstream of egl-1 and ced-9 and upstream of ced-3 apoptotic CC pathway (PubMed:26074078). Downstream of calreticulin crt-1 and CC upstream of ced-3 and independently of egl-1 and ced-9, plays a CC role in the initial steps of axonal regrowth following axotomy CC (PubMed:22629231). Together with ain-1, a component of the miRNA- CC induced-silencing complex (miRISC), and probably upstream of ced- CC 3, regulates temporal cell fate patterning during larval CC development (PubMed:25432023). May play a role in resistance to CC S.typhimurium-mediated infection (PubMed:11226309). CC {ECO:0000269|PubMed:10764728, ECO:0000269|PubMed:11226309, CC ECO:0000269|PubMed:17329362, ECO:0000269|PubMed:21901106, CC ECO:0000269|PubMed:22629231, ECO:0000269|PubMed:23106139, CC ECO:0000269|PubMed:25432023, ECO:0000269|PubMed:26074078, CC ECO:0000269|PubMed:3955651, ECO:0000269|PubMed:9927601}. CC -!- FUNCTION: Isoform a: Plays a major role in programmed cell death CC (PubMed:1286611, PubMed:8706125). egl-1 binds to and directly CC inhibits the activity of ced-9, releasing the cell death activator CC ced-4 from a ced-9/ced-4 containing protein complex and allowing CC ced-4 to induce caspase ced-3 autoproteolytic cleavage and CC activation (PubMed:15383288, PubMed:16208361, PubMed:20434985, CC PubMed:24065769). Also forms an holoenzyme with processed ced-3 CC enhancing ced-3 activity (PubMed:20434985). CC {ECO:0000269|PubMed:10688797, ECO:0000269|PubMed:1286611, CC ECO:0000269|PubMed:15383288, ECO:0000269|PubMed:16208361, CC ECO:0000269|PubMed:20434985, ECO:0000269|PubMed:24065769, CC ECO:0000269|PubMed:8706125}. CC -!- FUNCTION: Isoform b: Prevents programmed cell death. CC {ECO:0000269|PubMed:8706125}. CC -!- SUBUNIT: Associates as an asymmetric homodimer with ced-9 CC (PubMed:16208361, PubMed:9027313, PubMed:15383288). Upon release CC from ced-9, forms an octamer, known as the apoptosome, and CC interacts with ced-3; the interaction results in ced-3 CC autoproteolytic cleavage and activation (PubMed:20434985, CC PubMed:24065769). The octamer (a tetramer of an asymmetric dimer) CC also interacts with two processed ced-3 to form a stable CC holoenzyme (PubMed:20434985). Interacts with sex-determining CC protein fem-1 (PubMed:10764728). May form a complex composed of CC ced-3, ced-4 and mac-1 or of ced-9, ced-4 and mac-1 CC (PubMed:10101135). Within the complex, interacts with ced-4 CC (PubMed:10101135). {ECO:0000269|PubMed:10101135, CC ECO:0000269|PubMed:10764728, ECO:0000269|PubMed:15383288, CC ECO:0000269|PubMed:16208361, ECO:0000269|PubMed:20434985, CC ECO:0000269|PubMed:24065769, ECO:0000269|PubMed:9027313}. CC -!- INTERACTION: CC Q07817-1:BCL2L1 (xeno); NbExp=2; IntAct=EBI-536271, EBI-287195; CC P42573:ced-3; NbExp=13; IntAct=EBI-536271, EBI-494247; CC P41958:ced-9; NbExp=17; IntAct=EBI-494118, EBI-494110; CC Q9NAG4:mac-1; NbExp=8; IntAct=EBI-536271, EBI-2005767; CC Q20924:sun-1; NbExp=3; IntAct=EBI-494118, EBI-15599048; CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:10688797, CC ECO:0000269|PubMed:9027313}. Cytoplasm, perinuclear region CC {ECO:0000269|PubMed:10688797, ECO:0000269|PubMed:9027313}. Note=In CC non cell death induced cells, ced-9 is required for mitochondrial CC localization. Perinuclear in cell death induced cells. CC {ECO:0000269|PubMed:10688797, ECO:0000269|PubMed:9027313}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=b; Synonyms=Long; CC IsoId=P30429-1; Sequence=Displayed; CC Note=Minor transcript.; CC Name=a; Synonyms=Short; CC IsoId=P30429-2; Sequence=VSP_013199; CC Note=Major transcript.; CC -!- DEVELOPMENTAL STAGE: Abundantly expressed during embryogenesis and CC to a lesser extent in larvae and adults (PubMed:1286611). CC Expression starts at the 100-cell stage and persists through CC embryogenesis (at protein level) (PubMed:9027313). Not expressed CC in larvae and adults (at protein level) (PubMed:9027313). CC {ECO:0000269|PubMed:1286611, ECO:0000269|PubMed:9027313}. CC -!- DISRUPTION PHENOTYPE: Mutants exhibit a block in almost all CC programmed cell deaths that normally occur during development CC (PubMed:1286611). RNAi-mediated knockdown causes a defect in egg CC laying in a small proportion of animals (PubMed:25432023). Also CC causes a moderate increase in CEP neuron survival in response to CC high Al(3+) levels (PubMed:23106139). In an ain-1 mutant CC background, enhances the proportion of animals arrested at the CC larval stage, with egg-laying defects and with a ruptured vulva CC (PubMed:25432023). {ECO:0000269|PubMed:1286611, CC ECO:0000269|PubMed:23106139, ECO:0000269|PubMed:25432023}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; X69016; CAA48781.1; -; Genomic_DNA. DR EMBL; FO080789; CCD66781.1; -; Genomic_DNA. DR EMBL; FO080789; CCD66782.1; -; Genomic_DNA. DR PIR; S72566; S72566. DR RefSeq; NP_001021202.1; NM_001026031.2. [P30429-2] DR RefSeq; NP_001021203.1; NM_001026032.1. [P30429-1] DR UniGene; Cel.10679; -. DR PDB; 2A5Y; X-ray; 2.60 A; B/C=1-571. DR PDB; 3LQQ; X-ray; 3.53 A; A/B=1-571. DR PDB; 3LQR; X-ray; 3.90 A; A/B=1-571. DR PDB; 4M9S; X-ray; 3.21 A; A/B/C/D=1-571. DR PDB; 4M9X; X-ray; 3.34 A; A/B=1-571. DR PDB; 4M9Y; X-ray; 4.20 A; A/B=1-571. DR PDB; 4M9Z; X-ray; 3.40 A; A/B/C/D=1-571. DR PDBsum; 2A5Y; -. DR PDBsum; 3LQQ; -. DR PDBsum; 3LQR; -. DR PDBsum; 4M9S; -. DR PDBsum; 4M9X; -. DR PDBsum; 4M9Y; -. DR PDBsum; 4M9Z; -. DR ProteinModelPortal; P30429; -. DR SMR; P30429; -. DR BioGrid; 40877; 5. DR ComplexPortal; CPX-1358; ced-3-ced-4-mac-1 complex. DR ComplexPortal; CPX-1359; ced-4-ced-9-mac-1 complex. DR ComplexPortal; CPX-1360; ced-3-ced-4 caspase complex. DR ComplexPortal; CPX-399; ced-9-ced-4 complex. DR DIP; DIP-1016N; -. DR IntAct; P30429; 7. DR STRING; 6239.C35D10.9b; -. DR EPD; P30429; -. DR PaxDb; P30429; -. DR PeptideAtlas; P30429; -. DR PRIDE; P30429; -. DR EnsemblMetazoa; C35D10.9b.1; C35D10.9b.1; WBGene00000418. [P30429-1] DR EnsemblMetazoa; C35D10.9b.2; C35D10.9b.2; WBGene00000418. [P30429-1] DR GeneID; 175643; -. DR KEGG; cel:CELE_C35D10.9; -. DR UCSC; C35D10.9b; c. elegans. [P30429-1] DR CTD; 175643; -. DR WormBase; C35D10.9a; CE01203; WBGene00000418; ced-4. [P30429-2] DR WormBase; C35D10.9b; CE38154; WBGene00000418; ced-4. [P30429-1] DR eggNOG; KOG4658; Eukaryota. DR eggNOG; COG4886; LUCA. DR HOGENOM; HOG000111533; -. DR InParanoid; P30429; -. DR KO; K20105; -. DR OMA; AIMESYK; -. DR OrthoDB; EOG091G05PL; -. DR PhylomeDB; P30429; -. DR EvolutionaryTrace; P30429; -. DR PRO; PR:P30429; -. DR Proteomes; UP000001940; Chromosome III. DR Bgee; WBGene00000418; -. DR GO; GO:0008303; C:caspase complex; IMP:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:WormBase. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:WormBase. DR GO; GO:0043531; F:ADP binding; IEA:InterPro. DR GO; GO:0005524; F:ATP binding; IDA:WormBase. DR GO; GO:0051432; F:BH1 domain binding; IPI:WormBase. DR GO; GO:0051434; F:BH3 domain binding; IPI:WormBase. DR GO; GO:0089720; F:caspase binding; IPI:UniProtKB. DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0061133; F:endopeptidase activator activity; IDA:WormBase. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0016505; F:peptidase activator activity involved in apoptotic process; IDA:WormBase. DR GO; GO:0030042; P:actin filament depolymerization; IMP:UniProtKB. DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; IMP:UniProtKB. DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0008635; P:activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c; IBA:GO_Central. DR GO; GO:0006915; P:apoptotic process; IMP:UniProtKB. DR GO; GO:1902742; P:apoptotic process involved in development; IMP:UniProtKB. DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:UniProtKB. DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IGI:WormBase. DR GO; GO:0048598; P:embryonic morphogenesis; IGI:WormBase. DR GO; GO:0046716; P:muscle cell cellular homeostasis; IGI:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:WormBase. DR GO; GO:1904747; P:positive regulation of apoptotic process involved in development; IMP:UniProtKB. DR GO; GO:2001056; P:positive regulation of cysteine-type endopeptidase activity; IDA:WormBase. DR GO; GO:0010954; P:positive regulation of protein processing; IDA:UniProtKB. DR GO; GO:1905808; P:positive regulation of synapse disassembly; IMP:UniProtKB. DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB. DR GO; GO:0030155; P:regulation of cell adhesion; IMP:UniProtKB. DR GO; GO:0008361; P:regulation of cell size; IGI:WormBase. DR GO; GO:0043281; P:regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:WormBase. DR GO; GO:0040034; P:regulation of development, heterochronic; IGI:UniProtKB. DR GO; GO:0031647; P:regulation of protein stability; IGI:UniProtKB. DR Gene3D; 1.10.10.10; -; 1. DR InterPro; IPR016854; Apop_reg_Ced-4. DR InterPro; IPR001315; CARD. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR002182; NB-ARC. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR036388; WH-like_DNA-bd_sf. DR InterPro; IPR036390; WH_DNA-bd_sf. DR Pfam; PF00619; CARD; 1. DR Pfam; PF00931; NB-ARC; 1. DR PIRSF; PIRSF027202; Apop_reg_Ced-4; 1. DR SMART; SM00114; CARD; 1. DR SUPFAM; SSF46785; SSF46785; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR PROSITE; PS50209; CARD; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; ATP-binding; KW Complete proteome; Cytoplasm; Magnesium; Metal-binding; Mitochondrion; KW Nucleotide-binding; Reference proteome. FT CHAIN 1 571 Cell death protein 4. FT /FTId=PRO_0000089470. FT DOMAIN 1 91 CARD. {ECO:0000255|PROSITE- FT ProRule:PRU00046}. FT DOMAIN 133 439 NB-ARC. {ECO:0000255}. FT NP_BIND 162 167 ATP. {ECO:0000244|PDB:2A5Y, FT ECO:0000244|PDB:3LQQ, FT ECO:0000244|PDB:3LQR, FT ECO:0000244|PDB:4M9S, FT ECO:0000244|PDB:4M9X, FT ECO:0000244|PDB:4M9Y, FT ECO:0000244|PDB:4M9Z, FT ECO:0000269|PubMed:16208361, FT ECO:0000269|PubMed:20434985, FT ECO:0000269|PubMed:24065769}. FT METAL 166 166 Magnesium. {ECO:0000269|PubMed:16208361, FT ECO:0000269|PubMed:20434985}. FT BINDING 131 131 ATP; via carbonyl oxygen. FT {ECO:0000244|PDB:2A5Y, FT ECO:0000244|PDB:3LQQ, FT ECO:0000244|PDB:3LQR, FT ECO:0000244|PDB:4M9S, FT ECO:0000244|PDB:4M9X, FT ECO:0000244|PDB:4M9Y, FT ECO:0000244|PDB:4M9Z, FT ECO:0000269|PubMed:16208361, FT ECO:0000269|PubMed:20434985, FT ECO:0000269|PubMed:24065769}. FT BINDING 171 171 ATP. {ECO:0000244|PDB:4M9S, FT ECO:0000269|PubMed:24065769}. FT VAR_SEQ 212 234 ARVVSDTDDSHSITDFINRVLSR -> K (in isoform FT a). {ECO:0000305}. FT /FTId=VSP_013199. FT MUTAGEN 252 252 V->D: Loss of dimerization without FT affecting interaction with ced-9, loss of FT ced-3 activation and severe reduction in FT the number of cell corpses in embryos in FT a ced-1 mutant background; when FT associated with E-255 and E-256. FT {ECO:0000269|PubMed:16208361}. FT MUTAGEN 255 255 R->E: Severe reduction in the number of FT cell corpses in embryos in a ced-1 mutant FT background. Loss of dimerization without FT affecting interaction with ced-9, loss of FT ced-3 activation and severe reduction in FT the number of cell corpses in embryos in FT a ced-1 mutant background; when FT associated with E-252 and E-256. FT {ECO:0000269|PubMed:16208361}. FT MUTAGEN 256 256 M->E: Loss of dimerization without FT affecting interaction with ced-9, loss of FT ced-3 activation and severe reduction in FT the number of cell corpses in embryos in FT a ced-1 mutant background; when FT associated with E-252 and E-255. FT {ECO:0000269|PubMed:16208361}. FT MUTAGEN 272 273 DD->AA: Severe reduction in the number of FT cell corpses in embryos in a ced-1 mutant FT background. FT {ECO:0000269|PubMed:16208361}. FT MUTAGEN 280 280 I->N: In n1948; no effect on the FT interaction with mac-1. FT {ECO:0000269|PubMed:10101135}. FT MUTAGEN 416 416 A->W: Reduced interaction with ced-3. FT {ECO:0000269|PubMed:24065769}. FT HELIX 4 20 {ECO:0000244|PDB:2A5Y}. FT HELIX 23 26 {ECO:0000244|PDB:2A5Y}. FT HELIX 27 32 {ECO:0000244|PDB:2A5Y}. FT HELIX 38 45 {ECO:0000244|PDB:2A5Y}. FT STRAND 47 49 {ECO:0000244|PDB:2A5Y}. FT HELIX 50 64 {ECO:0000244|PDB:2A5Y}. FT STRAND 66 68 {ECO:0000244|PDB:2A5Y}. FT HELIX 69 77 {ECO:0000244|PDB:2A5Y}. FT HELIX 81 96 {ECO:0000244|PDB:2A5Y}. FT HELIX 101 104 {ECO:0000244|PDB:2A5Y}. FT TURN 105 108 {ECO:0000244|PDB:2A5Y}. FT HELIX 112 121 {ECO:0000244|PDB:2A5Y}. FT HELIX 134 147 {ECO:0000244|PDB:2A5Y}. FT STRAND 150 158 {ECO:0000244|PDB:2A5Y}. FT HELIX 165 175 {ECO:0000244|PDB:2A5Y}. FT TURN 181 183 {ECO:0000244|PDB:2A5Y}. FT STRAND 184 191 {ECO:0000244|PDB:2A5Y}. FT STRAND 196 198 {ECO:0000244|PDB:4M9X}. FT HELIX 199 211 {ECO:0000244|PDB:2A5Y}. FT TURN 234 236 {ECO:0000244|PDB:2A5Y}. FT STRAND 239 241 {ECO:0000244|PDB:4M9S}. FT HELIX 250 261 {ECO:0000244|PDB:2A5Y}. FT STRAND 267 274 {ECO:0000244|PDB:2A5Y}. FT HELIX 277 285 {ECO:0000244|PDB:2A5Y}. FT STRAND 289 296 {ECO:0000244|PDB:2A5Y}. FT HELIX 297 302 {ECO:0000244|PDB:2A5Y}. FT STRAND 307 311 {ECO:0000244|PDB:2A5Y}. FT HELIX 317 326 {ECO:0000244|PDB:2A5Y}. FT HELIX 336 348 {ECO:0000244|PDB:2A5Y}. FT HELIX 352 359 {ECO:0000244|PDB:2A5Y}. FT STRAND 364 366 {ECO:0000244|PDB:2A5Y}. FT HELIX 367 380 {ECO:0000244|PDB:2A5Y}. FT HELIX 381 384 {ECO:0000244|PDB:4M9S}. FT STRAND 389 395 {ECO:0000244|PDB:2A5Y}. FT HELIX 396 405 {ECO:0000244|PDB:2A5Y}. FT HELIX 409 414 {ECO:0000244|PDB:2A5Y}. FT HELIX 417 419 {ECO:0000244|PDB:2A5Y}. FT HELIX 429 435 {ECO:0000244|PDB:2A5Y}. FT HELIX 450 458 {ECO:0000244|PDB:2A5Y}. FT TURN 459 461 {ECO:0000244|PDB:2A5Y}. FT STRAND 462 464 {ECO:0000244|PDB:2A5Y}. FT STRAND 466 469 {ECO:0000244|PDB:2A5Y}. FT STRAND 471 473 {ECO:0000244|PDB:2A5Y}. FT STRAND 475 477 {ECO:0000244|PDB:2A5Y}. FT HELIX 480 487 {ECO:0000244|PDB:2A5Y}. FT HELIX 493 499 {ECO:0000244|PDB:2A5Y}. FT TURN 503 505 {ECO:0000244|PDB:2A5Y}. FT TURN 510 512 {ECO:0000244|PDB:4M9Z}. FT HELIX 555 558 {ECO:0000244|PDB:4M9S}. FT HELIX 559 562 {ECO:0000244|PDB:2A5Y}. SQ SEQUENCE 571 AA; 65336 MW; 6BE9893946B79E6C CRC64; MLCEIECRAL STAHTRLIHD FEPRDALTYL EGKNIFTEDH SELISKMSTR LERIANFLRI YRRQASELGP LIDFFNYNNQ SHLADFLEDY IDFAINEPDL LRPVVIAPQF SRQMLDRKLL LGNVPKQMTC YIREYHVDRV IKKLDEMCDL DSFFLFLHGR AGSGKSVIAS QALSKSDQLI GINYDSIVWL KDSGTAPKST FDLFTDILLM LARVVSDTDD SHSITDFINR VLSRSEDDLL NFPSVEHVTS VVLKRMICNA LIDRPNTLFV FDDVVQEETI RWAQELRLRC LVTTRDVEIS NAASQTCEFI EVTSLEIDEC YDFLEAYGMP MPVGEKEEDV LNKTIELSSG NPATLMMFFK SCEPKTFEKM AQLNNKLESR GLVGVECITP YSYKSLAMAL QRCVEVLSDE DRSALAFAVV MPPGVDIPVK LWSCVIPVDI CSNEEEQLDD EVADRLKRLS KRGALLSGKR MPVLTFKIDH IIHMFLKHVV DAQTIANGIS ILEQRLLEIG NNNVSVPERH IPSHFQKFRR SSASEMYPKT TEETVIRPED FPKFMQLHQK FYDSLKNFAC C // ID CRADD_HUMAN Reviewed; 199 AA. AC P78560; B7Z2Q5; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1997, sequence version 1. DT 18-JUL-2018, entry version 166. DE RecName: Full=Death domain-containing protein CRADD; DE AltName: Full=Caspase and RIP adapter with death domain; DE AltName: Full=RIP-associated protein with a death domain; GN Name=CRADD; Synonyms=RAIDD; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=9044836; RA Ahmad M., Srinivasula S.M., Wang L., Talanian R.V., Litwack G., RA Fernandes-Alnemri T., Alnemri E.S.; RT "CRADD, a novel human apoptotic adaptor molecule for caspase-2, and RT FasL/tumor necrosis factor receptor-interacting protein RIP."; RL Cancer Res. 57:615-619(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8985253; DOI=10.1038/385086a0; RA Duan H., Dixit V.M.; RT "RAIDD is a new 'death' adaptor molecule."; RL Nature 385:86-89(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., RA Kucherlapati R., Weinstock G., Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP INTERACTION WITH PIDD. RX PubMed=15073321; DOI=10.1126/science.1095432; RA Tinel A., Tschopp J.; RT "The PIDDosome, a protein complex implicated in activation of caspase- RT 2 in response to genotoxic stress."; RL Science 304:843-846(2004). RN [7] RP INTERACTION WITH PIDD. RX PubMed=16652156; DOI=10.1038/sj.onc.1209569; RA Vakifahmetoglu H., Olsson M., Orrenius S., Zhivotovsky B.; RT "Functional connection between p53 and caspase-2 is essential for RT apoptosis induced by DNA damage."; RL Oncogene 25:5683-5692(2006). RN [8] RP STRUCTURE BY NMR OF 1-100. RX PubMed=9695946; DOI=10.1016/S0092-8674(00)81417-8; RA Chou J.J., Matsuo H., Duan H., Wagner G.; RT "Solution structure of the RAIDD CARD and model for CARD/CARD RT interaction in caspase-2 and caspase-9 recruitment."; RL Cell 94:171-180(1998). RN [9] RP VARIANT MRT34 ARG-128. RX PubMed=22279524; DOI=10.1371/journal.pone.0028936; RA Puffenberger E.G., Jinks R.N., Sougnez C., Cibulskis K., Willert R.A., RA Achilly N.P., Cassidy R.P., Fiorentini C.J., Heiken K.F., RA Lawrence J.J., Mahoney M.H., Miller C.J., Nair D.T., Politi K.A., RA Worcester K.N., Setton R.A., Dipiazza R., Sherman E.A., Eastman J.T., RA Francklyn C., Robey-Bond S., Rider N.L., Gabriel S., Morton D.H., RA Strauss K.A.; RT "Genetic mapping and exome sequencing identify variants associated RT with five novel diseases."; RL PLoS ONE 7:E28936-E28936(2012). CC -!- FUNCTION: Apoptotic adaptor molecule specific for caspase-2 and CC FASL/TNF receptor-interacting protein RIP. In the presence of RIP CC and TRADD, CRADD recruits caspase-2 to the TNFR-1 signalling CC complex. CC -!- SUBUNIT: Interacts with PIDD. {ECO:0000269|PubMed:15073321, CC ECO:0000269|PubMed:16652156}. CC -!- INTERACTION: CC P35609:ACTN2; NbExp=3; IntAct=EBI-520375, EBI-77797; CC Q8NEU8:APPL2; NbExp=3; IntAct=EBI-520375, EBI-741261; CC Q8N3I7:BBS5; NbExp=3; IntAct=EBI-520375, EBI-2892592; CC P42575:CASP2; NbExp=17; IntAct=EBI-520375, EBI-520342; CC Q7L273:KCTD9; NbExp=3; IntAct=EBI-520375, EBI-4397613; CC Q9HB75:PIDD1; NbExp=6; IntAct=EBI-520375, EBI-520427; CC P14079:tax (xeno); NbExp=3; IntAct=EBI-520375, EBI-9675698; CC Q9BYV2:TRIM54; NbExp=3; IntAct=EBI-520375, EBI-2130429; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus CC {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P78560-1; Sequence=Displayed; CC Name=2; CC IsoId=P78560-2; Sequence=VSP_056892; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Constitutively expressed in most tissues, with CC particularly high expression in adult heart, testis, liver, CC skeletal muscle, fetal liver and kidney. CC -!- DOMAIN: Contains a death domain involved in the binding of RIP CC protein. CC -!- DOMAIN: The CARD domain mediates the interaction with caspase-2. CC -!- DISEASE: Mental retardation, autosomal recessive 34, with variant CC lissencephaly (MRT34) [MIM:614499]: A disorder characterized by CC significantly below average general intellectual functioning CC associated with impairments in adaptive behavior and manifested CC during the developmental period. MRT34 is a non-syndromic form. CC Affected individuals have mildly delayed development and CC significantly impaired cognitive function, precluding independent CC living and self-care. Speech is rudimentary, but articulate; CC autism is not present. {ECO:0000269|PubMed:22279524}. Note=The CC disease is caused by mutations affecting the gene represented in CC this entry. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; U84388; AAC50952.1; -; mRNA. DR EMBL; U79115; AAB42217.1; -; mRNA. DR EMBL; AK294986; BAH11941.1; -; mRNA. DR EMBL; AC012085; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC012464; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC025261; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC017042; AAH17042.1; -; mRNA. DR CCDS; CCDS9048.1; -. [P78560-1] DR RefSeq; NP_001307028.1; NM_001320099.1. [P78560-1] DR RefSeq; NP_001307029.1; NM_001320100.1. DR RefSeq; NP_001307030.1; NM_001320101.1. DR RefSeq; NP_003796.1; NM_003805.4. [P78560-1] DR RefSeq; XP_016875633.1; XM_017020144.1. [P78560-2] DR UniGene; Hs.38533; -. DR UniGene; Hs.591016; -. DR UniGene; Hs.660031; -. DR UniGene; Hs.719191; -. DR PDB; 2O71; X-ray; 2.00 A; A=94-199. DR PDB; 2OF5; X-ray; 3.20 A; A/B/C/D/E/F/G=94-199. DR PDB; 3CRD; NMR; -; A=1-100. DR PDBsum; 2O71; -. DR PDBsum; 2OF5; -. DR PDBsum; 3CRD; -. DR ProteinModelPortal; P78560; -. DR SMR; P78560; -. DR BioGrid; 114275; 22. DR CORUM; P78560; -. DR IntAct; P78560; 18. DR MINT; P78560; -. DR STRING; 9606.ENSP00000327647; -. DR iPTMnet; P78560; -. DR PhosphoSitePlus; P78560; -. DR BioMuta; CRADD; -. DR DMDM; 2498833; -. DR EPD; P78560; -. DR PaxDb; P78560; -. DR PeptideAtlas; P78560; -. DR PRIDE; P78560; -. DR ProteomicsDB; 57654; -. DR DNASU; 8738; -. DR Ensembl; ENST00000332896; ENSP00000327647; ENSG00000169372. [P78560-1] DR Ensembl; ENST00000542893; ENSP00000439068; ENSG00000169372. [P78560-1] DR Ensembl; ENST00000551065; ENSP00000448425; ENSG00000169372. [P78560-2] DR GeneID; 8738; -. DR KEGG; hsa:8738; -. DR UCSC; uc058rts.1; human. [P78560-1] DR CTD; 8738; -. DR DisGeNET; 8738; -. DR EuPathDB; HostDB:ENSG00000169372.12; -. DR GeneCards; CRADD; -. DR HGNC; HGNC:2340; CRADD. DR HPA; CAB005337; -. DR MalaCards; CRADD; -. DR MIM; 603454; gene. DR MIM; 614499; phenotype. DR neXtProt; NX_P78560; -. DR OpenTargets; ENSG00000169372; -. DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability. DR PharmGKB; PA26860; -. DR eggNOG; ENOG410IJAM; Eukaryota. DR eggNOG; ENOG4111SYE; LUCA. DR GeneTree; ENSGT00390000014448; -. DR HOGENOM; HOG000111965; -. DR HOVERGEN; HBG051112; -. DR InParanoid; P78560; -. DR KO; K02832; -. DR OMA; LGPEWEH; -. DR OrthoDB; EOG091G0M3P; -. DR PhylomeDB; P78560; -. DR TreeFam; TF333055; -. DR Reactome; R-HSA-6803207; TP53 Regulates Transcription of Caspase Activators and Caspases. DR SignaLink; P78560; -. DR ChiTaRS; CRADD; human. DR EvolutionaryTrace; P78560; -. DR GeneWiki; CRADD; -. DR GenomeRNAi; 8738; -. DR PRO; PR:P78560; -. DR Proteomes; UP000005640; Chromosome 12. DR Bgee; ENSG00000169372; -. DR CleanEx; HS_CRADD; -. DR ExpressionAtlas; P78560; baseline and differential. DR Genevisible; P78560; HS. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0070513; F:death domain binding; IPI:BHF-UCL. DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL. DR GO; GO:0030674; F:protein binding, bridging; IPI:BHF-UCL. DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IEA:Ensembl. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB. DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; IMP:UniProtKB. DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IC:BHF-UCL. DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0042981; P:regulation of apoptotic process; TAS:Reactome. DR CDD; cd08319; Death_RAIDD; 1. DR InterPro; IPR001315; CARD. DR InterPro; IPR037939; CRADD. DR InterPro; IPR037926; CRADD_Death. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR000488; Death_domain. DR PANTHER; PTHR15034; PTHR15034; 1. DR Pfam; PF00619; CARD; 1. DR Pfam; PF00531; Death; 1. DR SMART; SM00114; CARD; 1. DR SMART; SM00005; DEATH; 1. DR SUPFAM; SSF47986; SSF47986; 2. DR PROSITE; PS50209; CARD; 1. DR PROSITE; PS50017; DEATH_DOMAIN; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; Complete proteome; KW Cytoplasm; Disease mutation; Mental retardation; Nucleus; KW Reference proteome. FT CHAIN 1 199 Death domain-containing protein CRADD. FT /FTId=PRO_0000079326. FT DOMAIN 1 91 CARD. {ECO:0000255|PROSITE- FT ProRule:PRU00046}. FT DOMAIN 116 188 Death. {ECO:0000255|PROSITE- FT ProRule:PRU00064}. FT VAR_SEQ 101 199 DRLTGIPSHILNSSPSDRQINQLAQRLGPEWEPMVLSLGLS FT QTDIYRCKANHPHNVQSQVVEAFIRWRQRFGKQATFQSLHN FT GLRAVEVDPSLLLHMLE -> CWP (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_056892. FT VARIANT 128 128 G -> R (in MRT34; dbSNP:rs387906861). FT {ECO:0000269|PubMed:22279524}. FT /FTId=VAR_067536. FT HELIX 5 18 {ECO:0000244|PDB:3CRD}. FT HELIX 27 33 {ECO:0000244|PDB:3CRD}. FT HELIX 38 44 {ECO:0000244|PDB:3CRD}. FT STRAND 48 50 {ECO:0000244|PDB:3CRD}. FT HELIX 51 60 {ECO:0000244|PDB:3CRD}. FT TURN 61 63 {ECO:0000244|PDB:3CRD}. FT HELIX 69 75 {ECO:0000244|PDB:3CRD}. FT HELIX 79 92 {ECO:0000244|PDB:3CRD}. FT HELIX 110 112 {ECO:0000244|PDB:2O71}. FT HELIX 117 126 {ECO:0000244|PDB:2O71}. FT HELIX 131 137 {ECO:0000244|PDB:2O71}. FT HELIX 142 151 {ECO:0000244|PDB:2O71}. FT HELIX 156 171 {ECO:0000244|PDB:2O71}. FT HELIX 172 174 {ECO:0000244|PDB:2O71}. FT HELIX 177 186 {ECO:0000244|PDB:2O71}. FT HELIX 192 197 {ECO:0000244|PDB:2O71}. SQ SEQUENCE 199 AA; 22745 MW; 3437CC612C85E402 CRC64; MEARDKQVLR SLRLELGAEV LVEGLVLQYL YQEGILTENH IQEINAQTTG LRKTMLLLDI LPSRGPKAFD TFLDSLQEFP WVREKLKKAR EEAMTDLPAG DRLTGIPSHI LNSSPSDRQI NQLAQRLGPE WEPMVLSLGL SQTDIYRCKA NHPHNVQSQV VEAFIRWRQR FGKQATFQSL HNGLRAVEVD PSLLLHMLE // ID NLRP1_HUMAN Reviewed; 1473 AA. AC Q9C000; E9PE50; I6L9D9; Q9BZZ8; Q9BZZ9; Q9H5Z7; Q9H5Z8; Q9HAV8; AC Q9UFT4; Q9Y2E0; DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 18-JUL-2018, entry version 194. DE RecName: Full=NACHT, LRR and PYD domains-containing protein 1; DE AltName: Full=Caspase recruitment domain-containing protein 7; DE AltName: Full=Death effector filament-forming ced-4-like apoptosis protein; DE AltName: Full=Nucleotide-binding domain and caspase recruitment domain; GN Name=NLRP1; GN Synonyms=CARD7, DEFCAP, KIAA0926, NAC {ECO:0000303|PubMed:11113115}, GN NALP1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANTS HIS-155; SER-246; RP MET-878; VAL-1119; VAL-1184; LEU-1241 AND CYS-1366. RX PubMed=11270363; DOI=10.1038/sj.cdd.4400774; RA Bertin J., DiStefano P.S.; RT "The PYRIN domain: a novel motif found in apoptosis and inflammation RT proteins."; RL Cell Death Differ. 7:1273-1274(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=11250163; DOI=10.1016/S0960-9822(01)00056-2; RA Martinon F., Hofmann K., Tschopp J.; RT "The pyrin domain: a possible member of the death domain-fold family RT implicated in apoptosis and inflammation."; RL Curr. Biol. 11:R118-R120(2001). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND MUTAGENESIS OF RP LYS-340. RC TISSUE=Erythroleukemia; RX PubMed=11076957; DOI=10.1074/jbc.M009853200; RA Hlaing T., Guo R.-F., Dilley K.A., Loussia J.M., Morrish T.A., RA Shi M.M., Vincenz C., Ward P.A.; RT "Molecular cloning and characterization of DEFCAP-L and -S, two RT isoforms of a novel member of the mammalian Ced-4 family of apoptosis RT proteins."; RL J. Biol. Chem. 276:9230-9238(2001). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), FUNCTION, TISSUE RP SPECIFICITY, AND DEVELOPMENTAL STAGE. RC TISSUE=T-cell; RX PubMed=11113115; DOI=10.1074/jbc.M006309200; RA Chu Z.-L., Pio F., Xie Z., Welsh K., Krajewska M., Krajewski S., RA Godzik A., Reed J.C.; RT "A novel enhancer of the Apaf1 apoptosome involved in cytochrome c- RT dependent caspase activation and apoptosis."; RL J. Biol. Chem. 276:9239-9245(2001). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=10231032; DOI=10.1093/dnares/6.1.63; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., RA Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIII. RT The complete sequences of 100 new cDNA clones from brain which code RT for large proteins in vitro."; RL DNA Res. 6:63-70(1999). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 6 AND 7). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in RT the human lineage."; RL Nature 440:1045-1049(2006). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). RC TISSUE=Blood; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 282-1473 (ISOFORM 1), AND RP VARIANT VAL-1184. RC TISSUE=Uterus; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [10] RP PROTEIN SEQUENCE OF 1213-1224, FUNCTION, INTERACTION WITH PYCARD, RP INVOLVEMENT IN INFLAMMASOME COMPLEX, AUTOCATALYTIC CLEAVAGE, RP SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS VAL-1119 AND RP VAL-1184, AND MUTAGENESIS OF SER-1211; PHE-1212; SER-1213 AND RP PRO-1214. RX PubMed=22665479; DOI=10.1074/jbc.M112.378323; RA Finger J.N., Lich J.D., Dare L.C., Cook M.N., Brown K.K., RA Duraiswami C., Bertin J.J., Bertin J., Gough P.J.; RT "Autolytic proteolysis within the function to find domain (FIIND) is RT required for NLRP1 inflammasome activity."; RL J. Biol. Chem. 287:25030-25037(2012). RN [11] RP ERRATUM. RA Finger J.N., Lich J.D., Dare L.C., Cook M.N., Brown K.K., RA Duraiswami C., Bertin J.J., Bertin J., Gough P.J.; RL J. Biol. Chem. 287:31456-31456(2012). RN [12] RP FUNCTION, INTERACTION WITH CASP1; CASP5 AND PYCARD, AUTOINHIBITION, RP AND IDENTIFICATION IN INFLAMMASOME COMPLEX. RX PubMed=12191486; DOI=10.1016/S1097-2765(02)00599-3; RA Martinon F., Burns K., Tschopp J.; RT "The inflammasome: a molecular platform triggering activation of RT inflammatory caspases and processing of proIL-beta."; RL Mol. Cell 10:417-426(2002). RN [13] RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=15285719; DOI=10.1042/BJ20040867; RA Sanz C., Calasanz M.J., Andreu E., Richard C., Prosper F., RA Fernandez-Luna J.L.; RT "NALP1 is a transcriptional target for cAMP-response-element-binding RT protein (CREB) in myeloid leukaemia cells."; RL Biochem. J. 384:281-286(2004). RN [14] RP FUNCTION, AND MUTAGENESIS OF 339-GLY-LYS-340. RX PubMed=15212762; DOI=10.1016/j.cellsig.2004.02.006; RA Liu F., Lo C.F., Ning X., Kajkowski E.M., Jin M., Chiriac C., RA Gonzales C., Naureckiene S., Lock Y.-W., Pong K., Zaleska M.M., RA Jacobsen J.S., Silverman S., Ozenberger B.A.; RT "Expression of NALP1 in cerebellar granule neurons stimulates RT apoptosis."; RL Cell. Signal. 16:1013-1021(2004). RN [15] RP FUNCTION, INTERACTION WITH BCL2; BCL2L1; CASP5 AND PYCARD, SUBCELLULAR RP LOCATION, AND ACTIVATION BY MDP. RX PubMed=17418785; DOI=10.1016/j.cell.2007.01.045; RA Bruey J.M., Bruey-Sedano N., Luciano F., Zhai D., Balpai R., Xu C., RA Kress C.L., Bailly-Maitre B., Li X., Osterman A., Matsuzawa S., RA Terskikh A.V., Faustin B., Reed J.C.; RT "Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activation by RT interaction with NALP1."; RL Cell 129:45-56(2007). RN [16] RP INTERACTION WITH MEFV. RX PubMed=17431422; DOI=10.1038/sj.cdd.4402142; RA Papin S., Cuenin S., Agostini L., Martinon F., Werner S., Beer H.D., RA Grutter C., Grutter M., Tschopp J.; RT "The SPRY domain of Pyrin, mutated in familial Mediterranean fever RT patients, interacts with inflammasome components and inhibits proIL- RT 1beta processing."; RL Cell Death Differ. 14:1457-1466(2007). RN [17] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=17164409; DOI=10.1369/jhc.6A7101.2006; RA Kummer J.A., Broekhuizen R., Everett H., Agostini L., Kuijk L., RA Martinon F., van Bruggen R., Tschopp J.; RT "Inflammasome components NALP 1 and 3 Show distinct but separate RT expression profiles in human tissues suggesting a site-specific role RT in the inflammatory response."; RL J. Histochem. Cytochem. 55:443-452(2007). RN [18] RP FUNCTION, INTERACTION WITH CASP1, AUTOINHIBITION, HOMOMERIZATION, AND RP ACTIVATION BY MDP. RX PubMed=17349957; DOI=10.1016/j.molcel.2007.01.032; RA Faustin B., Lartigue L., Bruey J.-M., Luciano F., Sergienko E., RA Bailly-Maitre B., Volkmann N., Hanein D., Rouiller I., Reed J.C.; RT "Reconstituted NALP1 inflammasome reveals two-step mechanism of RT caspase-1 activation."; RL Mol. Cell 25:713-724(2007). RN [19] RP FUNCTION, INTERACTION WITH NOD2, AND ACTIVATION BY MDP. RX PubMed=18511561; DOI=10.1073/pnas.0802726105; RA Hsu L.C., Ali S.R., McGillivray S., Tseng P.H., Mariathasan S., RA Humke E.W., Eckmann L., Powell J.J., Nizet V., Dixit V.M., Karin M.; RT "A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion RT in response to Bacillus anthracis infection and muramyl dipeptide."; RL Proc. Natl. Acad. Sci. U.S.A. 105:7803-7808(2008). RN [20] RP LACK OF ACTIVATION BY ANTHRAX LETHAL TOXIN. RX PubMed=19651869; DOI=10.1128/IAI.00276-09; RA Liao K.C., Mogridge J.; RT "Expression of Nlrp1b inflammasome components in human fibroblasts RT confers susceptibility to anthrax lethal toxin."; RL Infect. Immun. 77:4455-4462(2009). RN [21] RP AUTOCATALYTIC CLEAVAGE, AND MUTAGENESIS OF SER-1213. RX PubMed=22087307; DOI=10.1371/journal.pone.0027396; RA D'Osualdo A., Weichenberger C.X., Wagner R.N., Godzik A., Wooley J., RA Reed J.C.; RT "CARD8 and NLRP1 undergo autoproteolytic processing through a ZU5-like RT domain."; RL PLoS ONE 6:E27396-E27396(2011). RN [22] RP INTERACTION WITH EIF2AK2. RX PubMed=22801494; DOI=10.1038/nature11290; RA Lu B., Nakamura T., Inouye K., Li J., Tang Y., Lundbaeck P., RA Valdes-Ferrer S.I., Olofsson P.S., Kalb T., Roth J., Zou Y., RA Erlandsson-Harris H., Yang H., Ting J.P., Wang H., Andersson U., RA Antoine D.J., Chavan S.S., Hotamisligil G.S., Tracey K.J.; RT "Novel role of PKR in inflammasome activation and HMGB1 release."; RL Nature 488:670-674(2012). RN [23] RP TISSUE SPECIFICITY, AND VARIANT MSPC THR-77. RX PubMed=23349227; DOI=10.1136/jmedgenet-2012-101325; RA Soler V.J., Tran-Viet K.N., Galiacy S.D., Limviphuvadh V., Klemm T.P., RA St Germain E., Fournie P.R., Guillaud C., Maurer-Stroh S., RA Hawthorne F., Suarez C., Kantelip B., Afshari N.A., Creveaux I., RA Luo X., Meng W., Calvas P., Cassagne M., Arne J.L., Rozen S.G., RA Malecaze F., Young T.L.; RT "Whole exome sequencing identifies a mutation for a novel form of RT corneal intraepithelial dyskeratosis."; RL J. Med. Genet. 50:246-254(2013). RN [24] RP INTERACTION WITH VACCINIA VIRUS PROTEIN F1. RX PubMed=16439990; DOI=10.1038/sj.cdd.4401853; RA Postigo A., Cross J.R., Downward J., Way M.; RT "Interaction of F1L with the BH3 domain of Bak is responsible for RT inhibiting vaccinia-induced apoptosis."; RL Cell Death Differ. 13:1651-1662(2006). RN [25] RP INDUCTION. RX PubMed=24439873; DOI=10.1016/j.ijcard.2013.12.201; RA Bleda S., de Haro J., Varela C., Esparza L., Ferruelo A., Acin F.; RT "NLRP1 inflammasome, and not NLRP3, is the key in the shift to RT proinflammatory state on endothelial cells in peripheral arterial RT disease."; RL Int. J. Cardiol. 172:E282-E284(2014). RN [26] RP INTERACTION WITH MEFV. RX PubMed=26347139; DOI=10.1083/jcb.201503023; RA Kimura T., Jain A., Choi S.W., Mandell M.A., Schroder K., Johansen T., RA Deretic V.; RT "TRIM-mediated precision autophagy targets cytoplasmic regulators of RT innate immunity."; RL J. Cell Biol. 210:973-989(2015). RN [27] RP INDUCTION BY ATF4. RX PubMed=26086088; DOI=10.1371/journal.pone.0130635; RA D'Osualdo A., Anania V.G., Yu K., Lill J.R., Kaufman R.J., RA Matsuzawa S., Reed J.C.; RT "Transcription factor ATF4 induces NLRP1 inflammasome expression RT during endoplasmic reticulum stress."; RL PLoS ONE 10:E0130635-E0130635(2015). RN [28] RP INVOLVEMENT IN AIADK, AND VARIANTS AIADK TRP-726 AND ARG-1214. RX PubMed=27965258; DOI=10.1136/annrheumdis-2016-210021; RA Grandemange S., Sanchez E., Louis-Plence P., Tran Mau-Them F., RA Bessis D., Coubes C., Frouin E., Seyger M., Girard M., Puechberty J., RA Costes V., Rodiere M., Carbasse A., Jeziorski E., Portales P., RA Sarrabay G., Mondain M., Jorgensen C., Apparailly F., Hoppenreijs E., RA Touitou I., Genevieve D.; RT "A new autoinflammatory and autoimmune syndrome associated with NLRP1 RT mutations: NAIAD (NLRP1-associated autoinflammation with arthritis and RT dyskeratosis)."; RL Ann. Rheum. Dis. 76:1191-1198(2017). RN [29] RP FUNCTION, TISSUE SPECIFICITY, VARIANTS MSPC THR-54; VAL-66 AND RP 787-PHE--ARG-843 DEL, AND CHARACTERIZATION OF VARIANTS MSPC THR-54; RP VAL-66 AND 787-PHE--ARG-843 DEL. RX PubMed=27662089; DOI=10.1016/j.cell.2016.09.001; RA Zhong F.L., Mamai O., Sborgi L., Boussofara L., Hopkins R., RA Robinson K., Szeverenyi I., Takeichi T., Balaji R., Lau A., Tye H., RA Roy K., Bonnard C., Ahl P.J., Jones L.A., Baker P., Lacina L., RA Otsuka A., Fournie P.R., Malecaze F., Lane E.B., Akiyama M., RA Kabashima K., Connolly J.E., Masters S.L., Soler V.J., Omar S.S., RA McGrath J.A., Nedelcu R., Gribaa M., Denguezli M., Saad A., Hiller S., RA Reversade B.; RT "Germline NLRP1 mutations cause skin inflammatory and cancer RT susceptibility syndromes via inflammasome activation."; RL Cell 167:187-202(2016). RN [30] RP STRUCTURE BY NMR OF 1-93. RX PubMed=14527388; DOI=10.1016/j.str.2003.08.009; RA Hiller S., Kohl A., Fiorito F., Herrmann T., Wider G., Tschopp J., RA Gruetter M.G., Wuethrich K.; RT "NMR structure of the apoptosis- and inflammation-related NALP1 pyrin RT domain."; RL Structure 11:1199-1205(2003). RN [31] RP INVOLVEMENT IN VAMAS1, AND VARIANT VAMAS1 HIS-155. RX PubMed=17377159; DOI=10.1056/NEJMoa061592; RA Jin Y., Mailloux C.M., Gowan K., Riccardi S.L., LaBerge G., RA Bennett D.C., Fain P.R., Spritz R.A.; RT "NALP1 in vitiligo-associated multiple autoimmune disease."; RL N. Engl. J. Med. 356:1216-1225(2007). RN [32] RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 1371-1467. RG Northeast structural genomics consortium (NESG); RT "Northeast structural genomics consortium target HR3486E."; RL Submitted (OCT-2009) to the PDB data bank. CC -!- FUNCTION: As the sensor component of the NLRP1 inflammasome, plays CC a crucial role in innate immunity and inflammation. In response to CC pathogens and other damage-associated signals, initiates the CC formation of the inflammasome polymeric complex, made of NLRP1, CC CASP1, and possibly PYCARD. Recruitment of proCASP1 to the CC inflammasome promotes its activation and CASP1-catalyzed IL1B and CC IL18 maturation and secretion in the extracellular milieu. CC Activation of NLRP1 inflammasome is also required for HMGB1 CC secretion. The active cytokines and HMGB1 stimulate inflammatory CC responses. Inflammasomes can also induce pyroptosis, an CC inflammatory form of programmed cell death (PubMed:22665479, CC PubMed:17418785). May be activated by muramyl dipeptide (MDP), a CC fragment of bacterial peptidoglycan, in a NOD2-dependent manner CC (PubMed:18511561). Contrary to its mouse ortholog, not activated CC by Bacillus anthracis lethal toxin (PubMed:19651869). It is CC unclear whether isoform 2 is involved in inflammasome formation. CC It is not cleaved within the FIIND domain, does not assemble into CC specks, nor promote IL1B release (PubMed:22665479). However, in an CC vitro cell-free system, it has been shown to be activated by MDP CC (PubMed:17349957). Binds ATP (PubMed:11113115, PubMed:15212762). CC {ECO:0000250|UniProtKB:A1Z198, ECO:0000269|PubMed:11113115, CC ECO:0000269|PubMed:15212762, ECO:0000269|PubMed:17349957, CC ECO:0000269|PubMed:17418785, ECO:0000269|PubMed:18511561, CC ECO:0000269|PubMed:19651869, ECO:0000269|PubMed:22665479, CC ECO:0000269|PubMed:27662089}. CC -!- SUBUNIT: Sensor component of NLRP1 inflammasomes. Inflammasomes CC are supramolecular complexes that assemble in the cytosol in CC response to pathogens and other damage-associated signals and play CC critical roles in innate immunity and inflammation. Classical CC inflammasomes consist of a signal sensor component, an adapter CC (ASC/PYCARD), which recruits an effector proinflammatory caspase CC (CASP1 and CASP5). This interaction initiates speck formation CC (nucleation) which greatly enhances further addition of soluble CC PYCARD molecules to the speck in a prion-like polymerization CC process. CASP1 filament formation increases local enzyme CC concentration, resulting in trans-autocleavage and activation. CC Active CASP1 then processes IL1B and IL18 precursors, leading to CC the release of mature cytokines in the extracellular milieu and CC inflammatory response. In NLRP1 inflammasome, the role of PYCARD CC is not clear. Following activation, NLRP1 can directly interact CC with CASP1 (possibly through CARD domain) to form a functional CC inflammasome, although the presence of PYCARD increases CASP1 CC activity (PubMed:17418785, PubMed:17349957). In a different CC experimental system, neither CASP1-binding, NLRP1 inflammasome CC speck formation, nor IL1B release were observed in the absence of CC PYCARD (PubMed:22665479, PubMed:12191486). Hence PYCARD may not be CC necessary for NLRP1 and CASP1 interaction, but is required for CC speck formation and full inflammasome activity (By similarity). CC Homomer (PubMed:17349957). Interacts (via LRR repeats) with BCL2 CC and BCL2L1 (via the loop between motifs BH4 and BH3); these CC interactions reduce NLRP1 inflammasome-induced CASP1 activation CC and IL1B release, possibly by impairing NLRP1 interaction with CC PYCARD (PubMed:17418785). Interacts with NOD2; this interaction is CC enhanced in the presence of muramyl dipeptide (MDP) and increases CC IL1B release (PubMed:18511561). Interacts with EIF2AK2/PKR; this CC interaction requires EIF2AK2 activity, is accompanied by EIF2AK2 CC autophosphorylation and promotes inflammasome assembly in response CC to danger-associated signals (By similarity). Interacts with MEFV; CC this interaction targets NLRP1 to degradation by autophagy, hence CC preventing excessive IL1B- and IL18-mediated inflammation CC (PubMed:17431422, PubMed:26347139). {ECO:0000250|UniProtKB:A1Z198, CC ECO:0000250|UniProtKB:Q2LKW6, ECO:0000269|PubMed:12191486, CC ECO:0000269|PubMed:17349957, ECO:0000269|PubMed:17418785, CC ECO:0000269|PubMed:17431422, ECO:0000269|PubMed:18511561, CC ECO:0000269|PubMed:22665479, ECO:0000269|PubMed:26347139}. CC -!- SUBUNIT: (Microbial infection) Interacts with vaccinia virus CC protein F1 (PubMed:16439990). {ECO:0000269|PubMed:16439990}. CC -!- INTERACTION: CC P10415:BCL2; NbExp=13; IntAct=EBI-1220518, EBI-77694; CC Q07817:BCL2L1; NbExp=9; IntAct=EBI-1220518, EBI-78035; CC Q07817-1:BCL2L1; NbExp=2; IntAct=EBI-1220518, EBI-287195; CC P29466:CASP1; NbExp=3; IntAct=EBI-1220518, EBI-516667; CC Q9ULZ3:PYCARD; NbExp=5; IntAct=EBI-1220518, EBI-751215; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol CC {ECO:0000269|PubMed:17418785}. Cytoplasm CC {ECO:0000269|PubMed:17164409}. Inflammasome CC {ECO:0000269|PubMed:12191486, ECO:0000269|PubMed:22665479}. CC Nucleus {ECO:0000269|PubMed:17164409}. Note=Nucleocytoplasmic CC distribution in lymphoid organs (probably in T-cells) and in CC neurons. In epithelial cells, predominantly cytoplasmic. CC {ECO:0000269|PubMed:17164409}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Name=1; Synonyms=NAC beta, DEFCAP-L, NALP1-L CC {ECO:0000303|PubMed:15285719}; CC IsoId=Q9C000-1; Sequence=Displayed; CC Name=2; Synonyms=NAC alpha, DEFCAP-S, NALP1-S CC {ECO:0000303|PubMed:15285719}, NLRP1deltaEx14; CC IsoId=Q9C000-2; Sequence=VSP_004327; CC Name=3; Synonyms=NAC gamma; CC IsoId=Q9C000-3; Sequence=VSP_004326, VSP_004327; CC Name=4; Synonyms=NAC delta; CC IsoId=Q9C000-4; Sequence=VSP_004326; CC Name=5; CC IsoId=Q9C000-5; Sequence=VSP_053803, VSP_053804, VSP_053805; CC Name=6; CC IsoId=Q9C000-6; Sequence=VSP_053802; CC Name=7; CC IsoId=Q9C000-7; Sequence=VSP_053801, VSP_053803, VSP_053804, CC VSP_053805; CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:11113115, CC PubMed:17164409). Abundantly expressed in primary immune cells CC (isoform 1 and isoform 2), including in neutrophils, CC monocytes/macrophages, dendritic cells (mostly Langerhans cells), CC and B- and T-lymphocytes (at protein level) (PubMed:15285719, CC PubMed:17164409). Strongly expressed in epithelial cells lining CC the glandular epithelium, such as that of the gastrointestinal CC tract (stomach, small intestine, colon), the respiratory tract CC (trachea and bronchi), and the endometrial and endocervical CC glands, gallbladder, prostate, and breast (at protein level). In CC testis, expressed in spermatogonia and primary spermatocytes, but CC not in Sertoli cells (at protein level). In the brain, expressed CC in neurons, in particular in pyramidal ones and in CC oligodendrocytes, but not detected in microglia (at protein level) CC (PubMed:17164409). Expressed in adult and fetal ocular tissues, CC including in adult and 24-week old fetal choroid, sclera, cornea, CC and optic nerve, as well as in adult retina and fetal CC retina/retinal pigment epithelium (PubMed:23349227). Highly CC expressed in the skin throughout the epidermis and in dermal CC fibroblasts, in both glabrous skin and plantar skin. It is CC detected in keratinocytes, but not in melanocytes. Expressed in CC epidermal appendages such as hair follicles (PubMed:27662089). CC {ECO:0000269|PubMed:11113115, ECO:0000269|PubMed:15285719, CC ECO:0000269|PubMed:17164409, ECO:0000269|PubMed:23349227, CC ECO:0000269|PubMed:27662089}. CC -!- DEVELOPMENTAL STAGE: Associated with differentiation in stratified CC epithelia of the skin, esophagus, intestine, and cervix, as well CC as in the prostate gland. Undetectable in undifferentiated basal CC cells, but expressed in differentiated luminal secretory cells CC (PubMed:11113115). Expressed in differentiated macrophages and CC granulocytes, but not their precursors (at protein level) CC (PubMed:11113115, PubMed:15285719). In testis, also associated CC with cell differentiation, with conflicting results. Expressed in CC spermatogonia and primary spermatocytes, but not in cells from CC later differentiation stages, including secondary spermatocytes, CC spermatids, and spermatozoa (at protein level) (PubMed:17164409). CC Not detected in spermatocytes, nor spermatids, and strongly CC expressed in spermatozoa (at protein level) (PubMed:11113115). CC {ECO:0000269|PubMed:11113115, ECO:0000269|PubMed:15285719, CC ECO:0000269|PubMed:17164409}. CC -!- INDUCTION: Up-regulated by ATF4 during endoplasmic reticulum (ER) CC stress response (PubMed:26086088). Up-regulated in arterial CC endothelial cells exposed to plasma from patients with peripheral CC arterial disease, but not to plasma from healthy controls CC (PubMed:24439873). {ECO:0000269|PubMed:24439873, CC ECO:0000269|PubMed:26086088}. CC -!- DOMAIN: The CARD domain, rather than the pyrin domain, is involved CC in the interaction with PYCARD, CASP1 and CASP5. CC {ECO:0000269|PubMed:12191486, ECO:0000269|PubMed:17349957, CC ECO:0000269|PubMed:22665479}. CC -!- DOMAIN: The leucine-rich repeat (LRR) domain may be involved in CC autoinhibition in the absence of activating signal, possibly CC through intramolecular interaction with the NACHT domain. CC {ECO:0000250|UniProtKB:Q9EPB4, ECO:0000269|PubMed:12191486, CC ECO:0000269|PubMed:17349957}. CC -!- DOMAIN: The FIIND (domain with function to find) region is CC involved in homomerization, but not in CASP1-binding (By CC similarity). Autocatalytic cleavage in this region occurs CC constitutively, prior to activation signals, and is required for CC inflammasome activity (IL1B release), possibly by facilitating CC CASP1 binding. Both N- and C-terminal fragments remain associated CC (PubMed:22665479, PubMed:22087307). {ECO:0000250|UniProtKB:Q2LKW6, CC ECO:0000269|PubMed:22087307, ECO:0000269|PubMed:22665479}. CC -!- DISEASE: Vitiligo-associated multiple autoimmune disease 1 CC (VAMAS1) [MIM:606579]: A disorder characterized by the association CC of vitiligo with several autoimmune and autoinflammatory diseases CC including autoimmune thyroid disease, rheumatoid arthritis and CC systemic lupus erythematosus. {ECO:0000269|PubMed:17377159}. CC Note=Disease susceptibility is associated with variations CC affecting the gene represented in this entry. CC -!- DISEASE: Palmoplantar carcinoma, multiple self-healing (MSPC) CC [MIM:615225]: An autosomal dominant disease characterized by CC keratopathy with neovascularization, bilateral corneal CC opacification, palmoplantar hyperkeratosis, dyshidrosis, CC dystrophic nails, and recurrent keratoacanthomas in palmoplantar CC skin as well as in conjunctival and corneal epithelia. In CC addition, patients experience a high susceptibility to malignant CC squamous cell carcinoma. {ECO:0000269|PubMed:23349227, CC ECO:0000269|PubMed:27662089}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Autoinflammation with arthritis and dyskeratosis (AIADK) CC [MIM:617388]: A disorder characterized by recurrent fever, diffuse CC skin dyskeratosis, autoinflammation, autoimmunity, arthritis and CC high transitional B-cell level. Inheritance can be autosomal CC dominant or autosomal recessive. {ECO:0000269|PubMed:27965258}. CC Note=The disease may be caused by mutations affecting the gene CC represented in this entry. CC -!- MISCELLANEOUS: In macrophages and dendritic cells, NLRP1 CC inflammasome activation of CASP1 and IL1B maturation can be CC dampened by direct contact with activated effector and memory T- CC cells. This effect may be mediated by hexameric TNF ligands, such CC as CD40LG. {ECO:0000250|UniProtKB:Q2LKW6}. CC -!- SIMILARITY: Belongs to the NLRP family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA76770.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC Sequence=BAB15469.1; Type=Frameshift; Positions=1241; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AF298548; AAG15254.1; -; mRNA. DR EMBL; AF310105; AAG30288.1; -; mRNA. DR EMBL; AF229059; AAK00748.1; -; mRNA. DR EMBL; AF229060; AAK00749.1; -; mRNA. DR EMBL; AF229061; AAK00750.1; -; mRNA. DR EMBL; AF229062; AAK00751.1; -; mRNA. DR EMBL; AB023143; BAA76770.2; ALT_INIT; mRNA. DR EMBL; AK026393; BAB15469.1; ALT_FRAME; mRNA. DR EMBL; AK026398; BAB15470.1; -; mRNA. DR EMBL; AC055839; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC051787; AAH51787.1; -; mRNA. DR EMBL; AL117470; CAB55945.1; -; mRNA. DR CCDS; CCDS32537.1; -. [Q9C000-5] DR CCDS; CCDS42244.1; -. [Q9C000-4] DR CCDS; CCDS42245.1; -. [Q9C000-2] DR CCDS; CCDS42246.1; -. [Q9C000-1] DR CCDS; CCDS58508.1; -. [Q9C000-3] DR PIR; T17255; T17255. DR RefSeq; NP_001028225.1; NM_001033053.2. [Q9C000-5] DR RefSeq; NP_055737.1; NM_014922.4. [Q9C000-2] DR RefSeq; NP_127497.1; NM_033004.3. [Q9C000-1] DR RefSeq; NP_127499.1; NM_033006.3. [Q9C000-4] DR RefSeq; NP_127500.1; NM_033007.3. [Q9C000-3] DR UniGene; Hs.652273; -. DR PDB; 1PN5; NMR; -; A=1-93. DR PDB; 3KAT; X-ray; 3.10 A; A=1371-1467. DR PDB; 4IFP; X-ray; 1.99 A; A/B/C=1379-1462. DR PDB; 4IM6; X-ray; 1.65 A; A=791-990. DR PDBsum; 1PN5; -. DR PDBsum; 3KAT; -. DR PDBsum; 4IFP; -. DR PDBsum; 4IM6; -. DR DisProt; DP00554; -. DR ProteinModelPortal; Q9C000; -. DR SMR; Q9C000; -. DR BioGrid; 116529; 13. DR CORUM; Q9C000; -. DR DIP; DIP-38407N; -. DR IntAct; Q9C000; 11. DR STRING; 9606.ENSP00000460475; -. DR BindingDB; Q9C000; -. DR ChEMBL; CHEMBL1741214; -. DR iPTMnet; Q9C000; -. DR PhosphoSitePlus; Q9C000; -. DR BioMuta; NLRP1; -. DR DMDM; 17380146; -. DR EPD; Q9C000; -. DR PaxDb; Q9C000; -. DR PeptideAtlas; Q9C000; -. DR PRIDE; Q9C000; -. DR ProteomicsDB; 79931; -. DR ProteomicsDB; 79932; -. [Q9C000-2] DR ProteomicsDB; 79933; -. [Q9C000-3] DR ProteomicsDB; 79934; -. [Q9C000-4] DR DNASU; 22861; -. DR Ensembl; ENST00000262467; ENSP00000262467; ENSG00000091592. [Q9C000-5] DR Ensembl; ENST00000269280; ENSP00000269280; ENSG00000091592. [Q9C000-2] DR Ensembl; ENST00000345221; ENSP00000324366; ENSG00000091592. [Q9C000-2] DR Ensembl; ENST00000354411; ENSP00000346390; ENSG00000091592. [Q9C000-4] DR Ensembl; ENST00000544378; ENSP00000442029; ENSG00000091592. [Q9C000-5] DR Ensembl; ENST00000571451; ENSP00000459661; ENSG00000091592. [Q9C000-2] DR Ensembl; ENST00000572272; ENSP00000460475; ENSG00000091592. [Q9C000-1] DR Ensembl; ENST00000577119; ENSP00000460216; ENSG00000091592. [Q9C000-3] DR Ensembl; ENST00000613500; ENSP00000483359; ENSG00000091592. [Q9C000-5] DR Ensembl; ENST00000617618; ENSP00000478516; ENSG00000091592. [Q9C000-1] DR Ensembl; ENST00000619223; ENSP00000484692; ENSG00000091592. [Q9C000-4] DR GeneID; 22861; -. DR KEGG; hsa:22861; -. DR UCSC; uc002gcg.2; human. [Q9C000-1] DR CTD; 22861; -. DR DisGeNET; 22861; -. DR EuPathDB; HostDB:ENSG00000091592.15; -. DR GeneCards; NLRP1; -. DR HGNC; HGNC:14374; NLRP1. DR HPA; CAB009189; -. DR HPA; HPA064431; -. DR MalaCards; NLRP1; -. DR MIM; 606579; phenotype. DR MIM; 606636; gene. DR MIM; 615225; phenotype. DR MIM; 617388; phenotype. DR neXtProt; NX_Q9C000; -. DR OpenTargets; ENSG00000091592; -. DR Orphanet; 352662; Corneal intraepithelial dyskeratosis with palmoplantar hyperkeratosis and laryngeal dyskeratosis. DR Orphanet; 3435; Vitiligo. DR Orphanet; 247871; Vitiligo-associated autoimmune disease. DR PharmGKB; PA162397797; -. DR eggNOG; ENOG410JAIN; Eukaryota. DR eggNOG; ENOG410YGKV; LUCA. DR GeneTree; ENSGT00900000140813; -. DR HOGENOM; HOG000230509; -. DR HOVERGEN; HBG052573; -. DR InParanoid; Q9C000; -. DR KO; K12798; -. DR OMA; LIMELWE; -. DR OrthoDB; EOG091G01QH; -. DR PhylomeDB; Q9C000; -. DR TreeFam; TF340267; -. DR Reactome; R-HSA-844455; The NLRP1 inflammasome. DR ChiTaRS; NLRP1; human. DR EvolutionaryTrace; Q9C000; -. DR GeneWiki; NLRP1; -. DR GenomeRNAi; 22861; -. DR PRO; PR:Q9C000; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; ENSG00000091592; -. DR CleanEx; HS_NLRP1; -. DR ExpressionAtlas; Q9C000; baseline and differential. DR Genevisible; Q9C000; HS. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005622; C:intracellular; IC:UniProtKB. DR GO; GO:0072558; C:NLRP1 inflammasome complex; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL. DR GO; GO:0005524; F:ATP binding; IDA:HGNC. DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; NAS:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB. DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:HGNC. DR GO; GO:0006915; P:apoptotic process; NAS:UniProtKB. DR GO; GO:0042742; P:defense response to bacterium; ISS:BHF-UCL. DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0051402; P:neuron apoptotic process; IDA:HGNC. DR GO; GO:1904784; P:NLRP1 inflammasome complex assembly; IMP:UniProtKB. DR GO; GO:0050718; P:positive regulation of interleukin-1 beta secretion; ISS:BHF-UCL. DR GO; GO:0050727; P:regulation of inflammatory response; IC:BHF-UCL. DR GO; GO:0032495; P:response to muramyl dipeptide; ISS:BHF-UCL. DR GO; GO:0016032; P:viral process; IEA:UniProtKB-KW. DR CDD; cd08330; CARD_ASC_NALP1; 1. DR Gene3D; 3.80.10.10; -; 1. DR InterPro; IPR001315; CARD. DR InterPro; IPR033516; CARD8/ASC/NALP1_CARD. DR InterPro; IPR004020; DAPIN. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR025307; FIIND_dom. DR InterPro; IPR001611; Leu-rich_rpt. DR InterPro; IPR032675; LRR_dom_sf. DR InterPro; IPR007111; NACHT_NTPase. DR InterPro; IPR027417; P-loop_NTPase. DR Pfam; PF00619; CARD; 1. DR Pfam; PF13553; FIIND; 1. DR Pfam; PF13516; LRR_6; 3. DR Pfam; PF05729; NACHT; 1. DR Pfam; PF02758; PYRIN; 1. DR SMART; SM01289; PYRIN; 1. DR SUPFAM; SSF47986; SSF47986; 2. DR SUPFAM; SSF52540; SSF52540; 2. DR PROSITE; PS50209; CARD; 1. DR PROSITE; PS50824; DAPIN; 1. DR PROSITE; PS51830; FIIND; 1. DR PROSITE; PS51450; LRR; 3. DR PROSITE; PS50837; NACHT; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Complete proteome; KW Cytoplasm; Direct protein sequencing; Disease mutation; KW Ectodermal dysplasia; Host-virus interaction; Immunity; Inflammasome; KW Inflammatory response; Innate immunity; Leucine-rich repeat; KW Nucleotide-binding; Nucleus; Polymorphism; Reference proteome; Repeat. FT CHAIN 1 1473 NACHT, LRR and PYD domains-containing FT protein 1. FT /FTId=PRO_0000096710. FT DOMAIN 1 92 Pyrin. {ECO:0000255|PROSITE- FT ProRule:PRU00061}. FT DOMAIN 328 637 NACHT. {ECO:0000255|PROSITE- FT ProRule:PRU00136}. FT REPEAT 809 830 LRR 1. FT REPEAT 838 858 LRR 2. FT REPEAT 866 887 LRR 3. FT REPEAT 895 915 LRR 4. FT REPEAT 923 944 LRR 5. FT REPEAT 950 973 LRR 6. FT DOMAIN 1079 1364 FIIND. {ECO:0000255|PROSITE- FT ProRule:PRU01174}. FT DOMAIN 1374 1463 CARD. {ECO:0000255|PROSITE- FT ProRule:PRU00046}. FT NP_BIND 334 341 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00136}. FT SITE 1186 1186 Trigger for autolytic processing. FT {ECO:0000269|PubMed:22665479}. FT SITE 1212 1213 Cleavage; by autolysis. FT {ECO:0000255|PROSITE-ProRule:PRU01174, FT ECO:0000269|PubMed:22665479}. FT VAR_SEQ 1 966 Missing (in isoform 7). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_053801. FT VAR_SEQ 1 734 Missing (in isoform 6). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_053802. FT VAR_SEQ 958 987 Missing (in isoform 3 and isoform 4). FT {ECO:0000303|PubMed:11113115}. FT /FTId=VSP_004326. FT VAR_SEQ 1044 1044 A -> AGKSH (in isoform 5 and isoform 7). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334}. FT /FTId=VSP_053803. FT VAR_SEQ 1262 1305 Missing (in isoform 2 and isoform 3). FT {ECO:0000303|PubMed:10231032, FT ECO:0000303|PubMed:11076957, FT ECO:0000303|PubMed:11113115, FT ECO:0000303|PubMed:11250163, FT ECO:0000303|PubMed:11270363}. FT /FTId=VSP_004327. FT VAR_SEQ 1354 1371 DLMPATTLIPPARIAVPS -> RNTSQPWNLRCNRDARRY FT (in isoform 5 and isoform 7). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334}. FT /FTId=VSP_053804. FT VAR_SEQ 1372 1473 Missing (in isoform 5 and isoform 7). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334}. FT /FTId=VSP_053805. FT VARIANT 54 54 A -> T (in MSPC; increased NLRP1- FT inflammasome complex assembly; altered FT protein folding; dbSNP:rs1057519492). FT {ECO:0000269|PubMed:27662089}. FT /FTId=VAR_078798. FT VARIANT 66 66 A -> V (in MSPC; increased NLRP1- FT inflammasome complex assembly; altered FT protein folding; dbSNP:rs1057519493). FT {ECO:0000269|PubMed:27662089}. FT /FTId=VAR_078799. FT VARIANT 77 77 M -> T (in MSPC; dbSNP:rs397514692). FT {ECO:0000269|PubMed:23349227}. FT /FTId=VAR_069901. FT VARIANT 155 155 L -> H (in VAMAS1; associated with FT disease susceptibility; FT dbSNP:rs12150220). FT {ECO:0000269|PubMed:11270363, FT ECO:0000269|PubMed:17377159}. FT /FTId=VAR_033239. FT VARIANT 246 246 T -> S (in dbSNP:rs11651595). FT {ECO:0000269|PubMed:11270363}. FT /FTId=VAR_024238. FT VARIANT 404 404 R -> Q (in dbSNP:rs3744718). FT /FTId=VAR_021886. FT VARIANT 726 726 R -> W (in AIADK; unknown pathological FT significance; dbSNP:rs776245016). FT {ECO:0000269|PubMed:27965258}. FT /FTId=VAR_078800. FT VARIANT 787 843 Missing (in MSPC; increased NLRP1- FT inflammasome complex assembly). FT {ECO:0000269|PubMed:27662089}. FT /FTId=VAR_078801. FT VARIANT 878 878 T -> M (in dbSNP:rs11657747). FT {ECO:0000269|PubMed:11270363}. FT /FTId=VAR_033240. FT VARIANT 1059 1059 V -> M (in dbSNP:rs2301582). FT /FTId=VAR_024239. FT VARIANT 1069 1069 H -> Y (in dbSNP:rs9907167). FT /FTId=VAR_033241. FT VARIANT 1119 1119 M -> V (no effect on autocatalytic FT processing, nor on IL1B release; FT dbSNP:rs35596958). FT {ECO:0000269|PubMed:11270363, FT ECO:0000269|PubMed:22665479}. FT /FTId=VAR_033242. FT VARIANT 1184 1184 M -> V (increased autocatalytic FT processing and IL1B release; FT dbSNP:rs11651270). FT {ECO:0000269|PubMed:11270363, FT ECO:0000269|PubMed:17974005, FT ECO:0000269|PubMed:22665479}. FT /FTId=VAR_033243. FT VARIANT 1214 1214 P -> R (in AIADK; unknown pathological FT significance; dbSNP:rs1057524876). FT {ECO:0000269|PubMed:27965258}. FT /FTId=VAR_078802. FT VARIANT 1241 1241 V -> L (in dbSNP:rs11653832). FT {ECO:0000269|PubMed:11270363}. FT /FTId=VAR_033244. FT VARIANT 1366 1366 R -> C (in dbSNP:rs2137722). FT {ECO:0000269|PubMed:11270363}. FT /FTId=VAR_020437. FT MUTAGEN 339 340 GK->EA: Loss of ATP binding. FT {ECO:0000269|PubMed:15212762}. FT MUTAGEN 340 340 K->L,S: No effect. FT {ECO:0000269|PubMed:11076957}. FT MUTAGEN 1168 1168 H->A: Complete loss of autocatalytic FT processing and of IL1B release. FT Autocatalytic processing cannot be FT restored by treatment with hydroxylamine. FT {ECO:0000269|PubMed:22665479}. FT MUTAGEN 1186 1186 H->A: Complete loss of autocatalytic FT processing and of IL1B release. FT Autocatalytic processing can be restored FT by treatment with hydroxylamine. FT {ECO:0000269|PubMed:22665479}. FT MUTAGEN 1211 1211 S->A: Partial loss of autocatalytic FT processing and of IL1B release. FT {ECO:0000269|PubMed:22665479}. FT MUTAGEN 1212 1212 F->A: Complete loss of autocatalytic FT processing and of IL1B release. FT {ECO:0000269|PubMed:22665479}. FT MUTAGEN 1213 1213 S->A: Complete loss of autocatalytic FT processing and of IL1B release. FT Autocatalytic processing cannot be FT restored by treatment with hydroxylamine. FT {ECO:0000269|PubMed:22087307, FT ECO:0000269|PubMed:22665479}. FT MUTAGEN 1213 1213 S->C: Complete loss of autocatalytic FT processing, which can be restored by FT treatment with hydroxylamine. FT {ECO:0000269|PubMed:22665479}. FT MUTAGEN 1214 1214 P->A: Partial loss of autocatalytic FT processing (50%) and of IL1B release FT (50%). {ECO:0000269|PubMed:22665479}. FT MUTAGEN 1249 1249 H->A: Complete loss of autocatalytic FT processing and IL1B release. FT Autocatalytic processing cannot be FT restored by treatment with hydroxylamine. FT {ECO:0000269|PubMed:22665479}. FT CONFLICT 287 287 P -> S (in Ref. 8; AAH51787). FT {ECO:0000305}. FT CONFLICT 782 782 T -> S (in Ref. 1; AAG15254). FT {ECO:0000305}. FT CONFLICT 995 995 T -> I (in Ref. 1; AAG15254). FT {ECO:0000305}. FT HELIX 9 15 {ECO:0000244|PDB:1PN5}. FT HELIX 18 31 {ECO:0000244|PDB:1PN5}. FT HELIX 50 60 {ECO:0000244|PDB:1PN5}. FT HELIX 63 77 {ECO:0000244|PDB:1PN5}. FT HELIX 80 85 {ECO:0000244|PDB:1PN5}. FT STRAND 88 91 {ECO:0000244|PDB:1PN5}. FT HELIX 794 804 {ECO:0000244|PDB:4IM6}. FT STRAND 812 814 {ECO:0000244|PDB:4IM6}. FT HELIX 822 833 {ECO:0000244|PDB:4IM6}. FT STRAND 840 843 {ECO:0000244|PDB:4IM6}. FT HELIX 851 862 {ECO:0000244|PDB:4IM6}. FT STRAND 869 871 {ECO:0000244|PDB:4IM6}. FT HELIX 878 889 {ECO:0000244|PDB:4IM6}. FT STRAND 898 900 {ECO:0000244|PDB:4IM6}. FT HELIX 908 910 {ECO:0000244|PDB:4IM6}. FT HELIX 911 920 {ECO:0000244|PDB:4IM6}. FT STRAND 926 928 {ECO:0000244|PDB:4IM6}. FT STRAND 931 933 {ECO:0000244|PDB:4IM6}. FT HELIX 935 946 {ECO:0000244|PDB:4IM6}. FT STRAND 955 957 {ECO:0000244|PDB:4IM6}. FT HELIX 965 977 {ECO:0000244|PDB:4IM6}. FT STRAND 982 984 {ECO:0000244|PDB:4IM6}. FT HELIX 1381 1384 {ECO:0000244|PDB:4IFP}. FT HELIX 1386 1392 {ECO:0000244|PDB:4IFP}. FT HELIX 1396 1403 {ECO:0000244|PDB:4IFP}. FT TURN 1405 1407 {ECO:0000244|PDB:4IFP}. FT HELIX 1410 1417 {ECO:0000244|PDB:4IFP}. FT STRAND 1419 1421 {ECO:0000244|PDB:4IFP}. FT HELIX 1422 1433 {ECO:0000244|PDB:4IFP}. FT HELIX 1438 1451 {ECO:0000244|PDB:4IFP}. FT HELIX 1453 1462 {ECO:0000244|PDB:4IFP}. SQ SEQUENCE 1473 AA; 165866 MW; 438F0DCE45C2562D CRC64; MAGGAWGRLA CYLEFLKKEE LKEFQLLLAN KAHSRSSSGE TPAQPEKTSG MEVASYLVAQ YGEQRAWDLA LHTWEQMGLR SLCAQAQEGA GHSPSFPYSP SEPHLGSPSQ PTSTAVLMPW IHELPAGCTQ GSERRVLRQL PDTSGRRWRE ISASLLYQAL PSSPDHESPS QESPNAPTST AVLGSWGSPP QPSLAPREQE APGTQWPLDE TSGIYYTEIR EREREKSEKG RPPWAAVVGT PPQAHTSLQP HHHPWEPSVR ESLCSTWPWK NEDFNQKFTQ LLLLQRPHPR SQDPLVKRSW PDYVEENRGH LIEIRDLFGP GLDTQEPRIV ILQGAAGIGK STLARQVKEA WGRGQLYGDR FQHVFYFSCR ELAQSKVVSL AELIGKDGTA TPAPIRQILS RPERLLFILD GVDEPGWVLQ EPSSELCLHW SQPQPADALL GSLLGKTILP EASFLITART TALQNLIPSL EQARWVEVLG FSESSRKEYF YRYFTDERQA IRAFRLVKSN KELWALCLVP WVSWLACTCL MQQMKRKEKL TLTSKTTTTL CLHYLAQALQ AQPLGPQLRD LCSLAAEGIW QKKTLFSPDD LRKHGLDGAI ISTFLKMGIL QEHPIPLSYS FIHLCFQEFF AAMSYVLEDE KGRGKHSNCI IDLEKTLEAY GIHGLFGAST TRFLLGLLSD EGEREMENIF HCRLSQGRNL MQWVPSLQLL LQPHSLESLH CLYETRNKTF LTQVMAHFEE MGMCVETDME LLVCTFCIKF SRHVKKLQLI EGRQHRSTWS PTMVVLFRWV PVTDAYWQIL FSVLKVTRNL KELDLSGNSL SHSAVKSLCK TLRRPRCLLE TLRLAGCGLT AEDCKDLAFG LRANQTLTEL DLSFNVLTDA GAKHLCQRLR QPSCKLQRLQ LVSCGLTSDC CQDLASVLSA SPSLKELDLQ QNNLDDVGVR LLCEGLRHPA CKLIRLGLDQ TTLSDEMRQE LRALEQEKPQ LLIFSRRKPS VMTPTEGLDT GEMSNSTSSL KRQRLGSERA ASHVAQANLK LLDVSKIFPI AEIAEESSPE VVPVELLCVP SPASQGDLHT KPLGTDDDFW GPTGPVATEV VDKEKNLYRV HFPVAGSYRW PNTGLCFVMR EAVTVEIEFC VWDQFLGEIN PQHSWMVAGP LLDIKAEPGA VEAVHLPHFV ALQGGHVDTS LFQMAHFKEE GMLLEKPARV ELHHIVLENP SFSPLGVLLK MIHNALRFIP VTSVVLLYHR VHPEEVTFHL YLIPSDCSIR KAIDDLEMKF QFVRIHKPPP LTPLYMGCRY TVSGSGSGML EILPKELELC YRSPGEDQLF SEFYVGHLGS GIRLQVKDKK DETLVWEALV KPGDLMPATT LIPPARIAVP SPLDAPQLLH FVDQYREQLI ARVTSVEVVL DKLHGQVLSQ EQYERVLAEN TRPSQMRKLF SLSQSWDRKC KDGLYQALKE THPHLIMELW EKGSKKGLLP LSS // ID NOD1_HUMAN Reviewed; 953 AA. AC Q9Y239; B4DTU3; Q549U4; Q8IWF5; DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 18-JUL-2018, entry version 184. DE RecName: Full=Nucleotide-binding oligomerization domain-containing protein 1; DE AltName: Full=Caspase recruitment domain-containing protein 4; GN Name=NOD1; Synonyms=CARD4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Endothelial cell; RX PubMed=10224040; DOI=10.1074/jbc.274.19.12955; RA Bertin J., Nir W.-J., Fischer C.M., Tayber O.V., Errada P.R., RA Grant J.R., Keilty J.J., Gosselin M.L., Robison K.E., Wong G.H.W., RA Glucksmann M.A., DiStefano P.S.; RT "Human CARD4 protein is a novel CED-4/Apaf-1 cell death family member RT that activates NF-kappaB."; RL J. Biol. Chem. 274:12955-12958(1999). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND MUTAGENESIS RP OF VAL-41 AND LYS-208. RC TISSUE=Mammary gland; RX PubMed=10329646; DOI=10.1074/jbc.274.21.14560; RA Inohara N., Koseki T., del Peso L., Hu Y., Yee C., Chen S., Carrio R., RA Merino J., Liu D., Ni J., Nunez G.; RT "Nod1, an Apaf-1-like activator of caspase-9 and nuclear factor- RT kappaB."; RL J. Biol. Chem. 274:14560-14567(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT RP HIS-447. RC TISSUE=Lymph; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION. RX PubMed=11058605; DOI=10.1074/jbc.M009728200; RA Inohara N., Ogura Y., Chen F.F., Muto A., Nunez G.; RT "Human Nod1 confers responsiveness to bacterial lipopolysaccharides."; RL J. Biol. Chem. 276:2551-2554(2001). RN [7] RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-208; ASP-711; HIS-788; RP GLY-792 AND GLN-877. RX PubMed=17970764; DOI=10.1111/j.1462-5822.2007.01062.x; RA Kufer T.A., Kremmer E., Adam A.C., Philpott D.J., Sansonetti P.J.; RT "The pattern-recognition molecule Nod1 is localized at the plasma RT membrane at sites of bacterial interaction."; RL Cell. Microbiol. 10:477-486(2008). RN [8] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ARHGEF2. RX PubMed=19043560; DOI=10.1371/journal.ppat.1000228; RA Fukazawa A., Alonso C., Kurachi K., Gupta S., Lesser C.F., RA McCormick B.A., Reinecker H.C.; RT "GEF-H1 mediated control of NOD1 dependent NF-kappaB activation by RT Shigella effectors."; RL PLoS Pathog. 4:E1000228-E1000228(2008). RN [9] RP FUNCTION, INTERACTION WITH NLRP10, AND MUTAGENESIS OF LYS-208 AND RP ASP-287. RX PubMed=22672233; DOI=10.1111/j.1462-5822.2012.01822.x; RA Lautz K., Damm A., Menning M., Wenger J., Adam A.C., Zigrino P., RA Kremmer E., Kufer T.A.; RT "NLRP10 enhances Shigella-induced pro-inflammatory responses."; RL Cell. Microbiol. 14:1568-1583(2012). RN [10] RP INTERACTION WITH RNF34, AND UBIQUITINATION BY RNF34. RX PubMed=25012219; DOI=10.1159/000362972; RA Zhang R., Zhao J., Song Y., Wang X., Wang L., Xu J., Song C., Liu F.; RT "The E3 ligase RNF34 is a novel negative regulator of the NOD1 RT pathway."; RL Cell. Physiol. Biochem. 33:1954-1962(2014). RN [11] RP STRUCTURE BY NMR OF 14-110. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the CARD domain in human caspase recruitment RT domain protein 4 (NOD1 protein)."; RL Submitted (DEC-2006) to the PDB data bank. RN [12] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 16-108, AND SUBUNIT. RX PubMed=17173864; DOI=10.1016/j.bbrc.2006.11.122; RA Coussens N.P., Mowers J.C., McDonald C., Nunez G., Ramaswamy S.; RT "Crystal structure of the Nod1 caspase activation and recruitment RT domain."; RL Biochem. Biophys. Res. Commun. 353:1-5(2007). RN [13] RP STRUCTURE BY NMR OF 15-138, FUNCTION, INTERACTION WITH RIPK2, AND RP MUTAGENESIS OF VAL-41; LEU-44; ASP-48; GLU-53; ASP-54; GLU-56 AND RP ARG-69. RX PubMed=17054981; DOI=10.1016/j.jmb.2006.09.067; RA Manon F., Favier A., Nunez G., Simorre J.P., Cusack S.; RT "Solution structure of NOD1 CARD and mutational analysis of its RT interaction with the CARD of downstream kinase RICK."; RL J. Mol. Biol. 365:160-174(2007). RN [14] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 9-106, AND SUBUNIT. RX PubMed=18186648; DOI=10.1021/bi7016602; RA Srimathi T., Robbins S.L., Dubas R.L., Hasegawa M., Inohara N., RA Park Y.C.; RT "Monomer/dimer transition of the caspase-recruitment domain of human RT Nod1."; RL Biochemistry 47:1319-1325(2008). CC -!- FUNCTION: Enhances caspase-9-mediated apoptosis. Induces NF-kappa- CC B activity via RIPK2 and IKK-gamma. Confers responsiveness to CC intracellular bacterial lipopolysaccharides (LPS). Forms an CC intracellular sensing system along with ARHGEF2 for the detection CC of microbial effectors during cell invasion by pathogens. Required CC for RHOA and RIPK2 dependent NF-kappa-B signaling pathway CC activation upon S.flexneri cell invasion. Involved not only in CC sensing peptidoglycan (PGN)-derived muropeptides but also in the CC activation of NF-kappa-B by Shigella effector proteins IpgB2 and CC OspB. Recruits NLRP10 to the cell membrane following bacterial CC infection. {ECO:0000269|PubMed:11058605, CC ECO:0000269|PubMed:17054981, ECO:0000269|PubMed:19043560, CC ECO:0000269|PubMed:22672233}. CC -!- SUBUNIT: Homodimer. Self-associates. Binds to caspase-9 and RIPK2 CC by CARD-CARD interaction. Interacts with ARHGEF2. Interacts with CC NLRP10 and recruits it to the cell membrane following invasive CC bacterial infection. Interacts with RNF34. CC {ECO:0000269|PubMed:17054981, ECO:0000269|PubMed:17173864, CC ECO:0000269|PubMed:18186648, ECO:0000269|PubMed:19043560, CC ECO:0000269|PubMed:22672233}. CC -!- INTERACTION: CC Self; NbExp=2; IntAct=EBI-1051262, EBI-1051262; CC P07900:HSP90AA1; NbExp=2; IntAct=EBI-1051262, EBI-296047; CC Q6UX06:OLFM4; NbExp=2; IntAct=EBI-1051262, EBI-2804156; CC O43353:RIPK2; NbExp=2; IntAct=EBI-1051262, EBI-358522; CC A0A0H3NF38:sspH2 (xeno); NbExp=4; IntAct=EBI-1051262, EBI-10689860; CC Q9Y2Z0:SUGT1; NbExp=5; IntAct=EBI-1051262, EBI-307008; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Apical cell CC membrane. Basolateral cell membrane. Note=Detected in the CC cytoplasm and at the cell membrane. Following bacterial infection, CC localizes to bacterial entry sites in the cell membrane. Recruited CC to the basolateral and apical membranes in polarized epithelial CC cells. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9Y239-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y239-2; Sequence=VSP_055825, VSP_055826; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Highly expressed in adult heart, skeletal CC muscle, pancreas, spleen and ovary. Also detected in placenta, CC lung, liver, kidney, thymus, testis, small intestine and colon. CC -!- PTM: Ubiquitinated. 'Lys-48'-linked polyubiquitination by RNF34 CC promotes proteasomal degradation and thereby negatively regulates CC NOD1 for instance in NF-kappa-B activition. CC {ECO:0000269|PubMed:25012219}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AF126484; AAD29125.1; -; mRNA. DR EMBL; AF149774; AAD43922.1; -; Genomic_DNA. DR EMBL; AF113925; AAD28350.1; -; mRNA. DR EMBL; AK300367; BAG62105.1; -; mRNA. DR EMBL; AC005154; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC006027; AAS46897.1; -; Genomic_DNA. DR EMBL; BC040339; AAH40339.1; -; mRNA. DR CCDS; CCDS5427.1; -. [Q9Y239-1] DR RefSeq; NP_006083.1; NM_006092.2. [Q9Y239-1] DR RefSeq; XP_005249625.1; XM_005249568.1. [Q9Y239-1] DR RefSeq; XP_005249629.1; XM_005249572.1. [Q9Y239-1] DR RefSeq; XP_006715696.1; XM_006715633.2. [Q9Y239-1] DR RefSeq; XP_011513381.1; XM_011515079.1. [Q9Y239-1] DR RefSeq; XP_011513382.1; XM_011515080.2. [Q9Y239-1] DR RefSeq; XP_011513383.1; XM_011515081.2. [Q9Y239-1] DR UniGene; Hs.405153; -. DR UniGene; Hs.738731; -. DR PDB; 2B1W; NMR; -; A=15-138. DR PDB; 2DBD; NMR; -; A=17-110. DR PDB; 2NSN; X-ray; 2.00 A; A=16-108. DR PDB; 2NZ7; X-ray; 1.90 A; A/B=9-106. DR PDB; 4E9M; X-ray; 2.15 A; A/B/C/D/E/F=2-138. DR PDB; 4JQW; X-ray; 2.90 A; A=16-108. DR PDBsum; 2B1W; -. DR PDBsum; 2DBD; -. DR PDBsum; 2NSN; -. DR PDBsum; 2NZ7; -. DR PDBsum; 4E9M; -. DR PDBsum; 4JQW; -. DR ProteinModelPortal; Q9Y239; -. DR SMR; Q9Y239; -. DR BioGrid; 115664; 28. DR CORUM; Q9Y239; -. DR DIP; DIP-41064N; -. DR IntAct; Q9Y239; 28. DR MINT; Q9Y239; -. DR STRING; 9606.ENSP00000222823; -. DR BindingDB; Q9Y239; -. DR ChEMBL; CHEMBL1293222; -. DR GuidetoPHARMACOLOGY; 1762; -. DR iPTMnet; Q9Y239; -. DR PhosphoSitePlus; Q9Y239; -. DR BioMuta; NOD1; -. DR DMDM; 20137579; -. DR EPD; Q9Y239; -. DR PaxDb; Q9Y239; -. DR PeptideAtlas; Q9Y239; -. DR PRIDE; Q9Y239; -. DR ProteomicsDB; 85636; -. DR Ensembl; ENST00000222823; ENSP00000222823; ENSG00000106100. [Q9Y239-1] DR GeneID; 10392; -. DR KEGG; hsa:10392; -. DR UCSC; uc003tav.4; human. [Q9Y239-1] DR CTD; 10392; -. DR DisGeNET; 10392; -. DR EuPathDB; HostDB:ENSG00000106100.10; -. DR GeneCards; NOD1; -. DR HGNC; HGNC:16390; NOD1. DR HPA; HPA074367; -. DR MIM; 605980; gene. DR neXtProt; NX_Q9Y239; -. DR OpenTargets; ENSG00000106100; -. DR PharmGKB; PA162398098; -. DR eggNOG; KOG4308; Eukaryota. DR eggNOG; ENOG410ZBX3; LUCA. DR GeneTree; ENSGT00860000133673; -. DR HOGENOM; HOG000113813; -. DR HOVERGEN; HBG050793; -. DR InParanoid; Q9Y239; -. DR KO; K08727; -. DR OMA; NDYGVRE; -. DR OrthoDB; EOG091G0I7O; -. DR PhylomeDB; Q9Y239; -. DR TreeFam; TF352118; -. DR Reactome; R-HSA-168638; NOD1/2 Signaling Pathway. DR Reactome; R-HSA-445989; TAK1 activates NFkB by phosphorylation and activation of IKKs complex. DR Reactome; R-HSA-450302; activated TAK1 mediates p38 MAPK activation. DR Reactome; R-HSA-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1. DR Reactome; R-HSA-5689896; Ovarian tumor domain proteases. DR Reactome; R-HSA-9020702; Interleukin-1 signaling. DR SignaLink; Q9Y239; -. DR SIGNOR; Q9Y239; -. DR ChiTaRS; NOD1; human. DR EvolutionaryTrace; Q9Y239; -. DR GeneWiki; NOD1; -. DR GenomeRNAi; 10392; -. DR PRO; PR:Q9Y239; -. DR Proteomes; UP000005640; Chromosome 7. DR Bgee; ENSG00000106100; -. DR CleanEx; HS_NOD1; -. DR ExpressionAtlas; Q9Y239; baseline and differential. DR Genevisible; Q9Y239; HS. DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0050700; F:CARD domain binding; IDA:MGI. DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; TAS:ProtInc. DR GO; GO:0042802; F:identical protein binding; IDA:MGI. DR GO; GO:0042834; F:peptidoglycan binding; TAS:HGNC. DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB. DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:MGI. DR GO; GO:0000187; P:activation of MAPK activity; TAS:Reactome. DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc. DR GO; GO:0071225; P:cellular response to muramyl dipeptide; IMP:UniProtKB. DR GO; GO:0006952; P:defense response; TAS:HGNC. DR GO; GO:0042742; P:defense response to bacterium; IDA:HGNC. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IEA:Ensembl. DR GO; GO:0016045; P:detection of bacterium; IDA:HGNC. DR GO; GO:0009595; P:detection of biotic stimulus; TAS:HGNC. DR GO; GO:0006954; P:inflammatory response; TAS:HGNC. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; TAS:Reactome. DR GO; GO:0042228; P:interleukin-8 biosynthetic process; IDA:HGNC. DR GO; GO:0035556; P:intracellular signal transduction; IDA:HGNC. DR GO; GO:0007254; P:JNK cascade; TAS:Reactome. DR GO; GO:0070423; P:nucleotide-binding oligomerization domain containing signaling pathway; TAS:Reactome. DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:MGI. DR GO; GO:0002606; P:positive regulation of dendritic cell antigen processing and presentation; ISS:BHF-UCL. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:MGI. DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IEA:Ensembl. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl. DR GO; GO:0046330; P:positive regulation of JNK cascade; IEA:Ensembl. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB. DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IMP:UniProtKB. DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; IEA:Ensembl. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl. DR GO; GO:1904417; P:positive regulation of xenophagy; IEA:Ensembl. DR GO; GO:0051259; P:protein complex oligomerization; TAS:HGNC. DR GO; GO:0007165; P:signal transduction; TAS:HGNC. DR Gene3D; 3.80.10.10; -; 2. DR InterPro; IPR001315; CARD. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR001611; Leu-rich_rpt. DR InterPro; IPR032675; LRR_dom_sf. DR InterPro; IPR007111; NACHT_NTPase. DR Pfam; PF00619; CARD; 1. DR Pfam; PF13516; LRR_6; 4. DR Pfam; PF05729; NACHT; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR PROSITE; PS50209; CARD; 1. DR PROSITE; PS50837; NACHT; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; ATP-binding; KW Cell membrane; Complete proteome; Cytoplasm; Immunity; KW Innate immunity; Leucine-rich repeat; Membrane; Nucleotide-binding; KW Polymorphism; Reference proteome; Repeat; Ubl conjugation. FT CHAIN 1 953 Nucleotide-binding oligomerization FT domain-containing protein 1. FT /FTId=PRO_0000144077. FT DOMAIN 15 105 CARD. {ECO:0000255|PROSITE- FT ProRule:PRU00046}. FT DOMAIN 196 531 NACHT. {ECO:0000255|PROSITE- FT ProRule:PRU00136}. FT REPEAT 632 656 LRR 1. FT REPEAT 702 725 LRR 2. FT REPEAT 727 750 LRR 3. FT REPEAT 755 778 LRR 4. FT REPEAT 783 806 LRR 5. FT REPEAT 839 862 LRR 6. FT REPEAT 867 891 LRR 7. FT REPEAT 895 918 LRR 8. FT REPEAT 923 946 LRR 9. FT NP_BIND 202 209 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00136}. FT VAR_SEQ 195 249 GETIFILGDAGVGKSMLLQRLQSLWATGRLDAGVKFFFHFR FT CRMFSCFKESDRLC -> AASRKVTGCVCRTCSSSTTATQS FT GTPRRCLPSCCASPTWPSSPSMAWTSCTRTWT (in FT isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_055825. FT VAR_SEQ 250 953 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_055826. FT VARIANT 266 266 E -> K (in dbSNP:rs2075820). FT /FTId=VAR_020371. FT VARIANT 372 372 D -> N (in dbSNP:rs5743342). FT /FTId=VAR_053624. FT VARIANT 447 447 R -> H (in dbSNP:rs2975634). FT {ECO:0000269|PubMed:15489334}. FT /FTId=VAR_053625. FT VARIANT 605 605 R -> W (in dbSNP:rs5743345). FT /FTId=VAR_053626. FT VARIANT 610 610 A -> T (in dbSNP:rs5743346). FT /FTId=VAR_053627. FT MUTAGEN 41 41 V->A: Abolishes interaction with FT RIPK2/RICK. {ECO:0000269|PubMed:10329646, FT ECO:0000269|PubMed:17054981}. FT MUTAGEN 41 41 V->Q: Abolishes caspase-9 activation. FT {ECO:0000269|PubMed:10329646, FT ECO:0000269|PubMed:17054981}. FT MUTAGEN 44 44 L->A: Abolishes activation of NF-kappa-B. FT No effect on interaction with RIPK2. FT {ECO:0000269|PubMed:17054981}. FT MUTAGEN 48 48 D->K: Abolishes activation of NF-kappa-B. FT No effect on interaction with RIPK2. FT {ECO:0000269|PubMed:17054981}. FT MUTAGEN 53 53 E->K: No effect on activation of NF- FT kappa-B. Abolishes interaction with FT RIPK2. {ECO:0000269|PubMed:17054981}. FT MUTAGEN 54 54 D->K: Abolishes activation of NF-kappa-B. FT Abolishes interaction with RIPK2. FT {ECO:0000269|PubMed:17054981}. FT MUTAGEN 56 56 E->K: Abolishes activation of NF-kappa-B. FT Abolishes interaction with RIPK2. FT {ECO:0000269|PubMed:17054981}. FT MUTAGEN 69 69 R->E: Abolishes activation of NF-kappa-B. FT Abolishes interaction with RIPK2. FT {ECO:0000269|PubMed:17054981}. FT MUTAGEN 208 208 K->R: Reduces caspase-9 activation. FT Reduced binding affinity for NLRP10. Does FT not associate with cell membrane. FT {ECO:0000269|PubMed:10329646, FT ECO:0000269|PubMed:17970764, FT ECO:0000269|PubMed:22672233}. FT MUTAGEN 287 287 D->A: Reduced binding affinity for FT NLRP10. {ECO:0000269|PubMed:22672233}. FT MUTAGEN 711 711 D->S: Does not associate with cell FT membrane. {ECO:0000269|PubMed:17970764}. FT MUTAGEN 788 788 H->S: No effect on association with cell FT membrane. {ECO:0000269|PubMed:17970764}. FT MUTAGEN 792 792 G->S: Does not associate with cell FT membrane. {ECO:0000269|PubMed:17970764}. FT MUTAGEN 877 877 Q->S: Does not associate with cell FT membrane. {ECO:0000269|PubMed:17970764}. FT HELIX 18 25 {ECO:0000244|PDB:2NZ7}. FT HELIX 27 33 {ECO:0000244|PDB:2NZ7}. FT HELIX 38 46 {ECO:0000244|PDB:2NZ7}. FT HELIX 52 59 {ECO:0000244|PDB:2NZ7}. FT STRAND 61 63 {ECO:0000244|PDB:4E9M}. FT HELIX 64 78 {ECO:0000244|PDB:2NZ7}. FT HELIX 80 95 {ECO:0000244|PDB:2NZ7}. FT HELIX 98 100 {ECO:0000244|PDB:2NZ7}. FT HELIX 101 105 {ECO:0000244|PDB:2NZ7}. SQ SEQUENCE 953 AA; 107691 MW; 0A9DF5FC6487E21A CRC64; MEEQGHSEME IIPSESHPHI QLLKSNRELL VTHIRNTQCL VDNLLKNDYF SAEDAEIVCA CPTQPDKVRK ILDLVQSKGE EVSEFFLYLL QQLADAYVDL RPWLLEIGFS PSLLTQSKVV VNTDPVSRYT QQLRHHLGRD SKFVLCYAQK EELLLEEIYM DTIMELVGFS NESLGSLNSL ACLLDHTTGI LNEQGETIFI LGDAGVGKSM LLQRLQSLWA TGRLDAGVKF FFHFRCRMFS CFKESDRLCL QDLLFKHYCY PERDPEEVFA FLLRFPHVAL FTFDGLDELH SDLDLSRVPD SSCPWEPAHP LVLLANLLSG KLLKGASKLL TARTGIEVPR QFLRKKVLLR GFSPSHLRAY ARRMFPERAL QDRLLSQLEA NPNLCSLCSV PLFCWIIFRC FQHFRAAFEG SPQLPDCTMT LTDVFLLVTE VHLNRMQPSS LVQRNTRSPV ETLHAGRDTL CSLGQVAHRG MEKSLFVFTQ EEVQASGLQE RDMQLGFLRA LPELGPGGDQ QSYEFFHLTL QAFFTAFFLV LDDRVGTQEL LRFFQEWMPP AGAATTSCYP PFLPFQCLQG SGPAREDLFK NKDHFQFTNL FLCGLLSKAK QKLLRHLVPA AALRRKRKAL WAHLFSSLRG YLKSLPRVQV ESFNQVQAMP TFIWMLRCIY ETQSQKVGQL AARGICANYL KLTYCNACSA DCSALSFVLH HFPKRLALDL DNNNLNDYGV RELQPCFSRL TVLRLSVNQI TDGGVKVLSE ELTKYKIVTY LGLYNNQITD VGARYVTKIL DECKGLTHLK LGKNKITSEG GKYLALAVKN SKSISEVGMW GNQVGDEGAK AFAEALRNHP SLTTLSLASN GISTEGGKSL ARALQQNTSL EILWLTQNEL NDEVAESLAE MLKVNQTLKH LWLIQNQITA KGTAQLADAL QSNTGITEIC LNGNLIKPEE AKVYEDEKRI ICF // ID NOL3_HUMAN Reviewed; 208 AA. AC O60936; B4DFL0; O60937; DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot. DT 01-APR-2015, sequence version 2. DT 18-JUL-2018, entry version 156. DE RecName: Full=Nucleolar protein 3 {ECO:0000312|HGNC:HGNC:7869}; DE AltName: Full=Apoptosis repressor with CARD {ECO:0000305|PubMed:9560245}; DE AltName: Full=Muscle-enriched cytoplasmic protein {ECO:0000305|PubMed:10196175}; DE Short=Myp {ECO:0000303|PubMed:10196175}; DE AltName: Full=Nucleolar protein of 30 kDa {ECO:0000303|PubMed:10196175}; DE Short=Nop30 {ECO:0000303|PubMed:10196175}; GN Name=NOL3 {ECO:0000312|HGNC:HGNC:7869}; GN Synonyms=ARC {ECO:0000303|PubMed:9560245}, GN NOP {ECO:0000303|PubMed:10196175}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND INTERACTION WITH CASP2 AND RP CASP8. RX PubMed=9560245; DOI=10.1073/pnas.95.9.5156; RA Koseki T., Inohara N., Chen S., Nunez G.; RT "ARC, an inhibitor of apoptosis expressed in skeletal muscle and heart RT that interacts selectively with caspases."; RL Proc. Natl. Acad. Sci. U.S.A. 95:5156-5160(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), RP SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH SFRS9, AND FUNCTION RP (ISOFORM 1). RC TISSUE=Cervix carcinoma; RX PubMed=10196175; DOI=10.1074/jbc.274.16.10951; RA Stoss O., Schwaiger F.-W., Cooper T.A., Stamm S.; RT "Alternative splicing determines the intracellular localization of the RT novel nuclear protein Nop30 and its interaction with the splicing RT factor SRp30c."; RL J. Biol. Chem. 274:10951-10962(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain cortex; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., RA Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Kidney; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP FUNCTION (ISOFORM 2), INTERACTION WITH BAX, AND DOMAIN. RX PubMed=15004034; DOI=10.1074/jbc.M400695200; RA Gustafsson A.B., Tsai J.G., Logue S.E., Crow M.T., Gottlieb R.A.; RT "Apoptosis repressor with caspase recruitment domain protects against RT cell death by interfering with Bax activation."; RL J. Biol. Chem. 279:21233-21238(2004). RN [8] RP FUNCTION (ISOFORM 2), DOMAIN, AND INTERACTION WITH CASP8. RX PubMed=15509781; DOI=10.1128/MCB.24.22.9763-9770.2004; RA Jo D.G., Jun J.I., Chang J.W., Hong Y.M., Song S., Cho D.H., RA Shim S.M., Lee H.J., Cho C., Kim D.H., Jung Y.K.; RT "Calcium binding of ARC mediates regulation of caspase 8 and cell RT death."; RL Mol. Cell. Biol. 24:9763-9770(2004). RN [9] RP INDUCTION. RX PubMed=16505176; DOI=10.1161/CIRCULATIONAHA.105.576785; RA Donath S., Li P., Willenbockel C., Al-Saadi N., Gross V., Willnow T., RA Bader M., Martin U., Bauersachs J., Wollert K.C., Dietz R., RA von Harsdorf R.; RT "Apoptosis repressor with caspase recruitment domain is required for RT cardioprotection in response to biomechanical and ischemic stress."; RL Circulation 113:1203-1212(2006). RN [10] RP INDUCTION, UBIQUITINATION, AND MUTAGENESIS OF LYS-17; LYS-68 AND RP LYS-163. RX PubMed=17142452; DOI=10.1074/jbc.M609186200; RA Nam Y.J., Mani K., Wu L., Peng C.F., Calvert J.W., Foo R.S., RA Krishnamurthy B., Miao W., Ashton A.W., Lefer D.J., Kitsis R.N.; RT "The apoptosis inhibitor ARC undergoes ubiquitin-proteasomal-mediated RT degradation in response to death stimuli: identification of a RT degradation-resistant mutant."; RL J. Biol. Chem. 282:5522-5528(2007). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [12] RP MYRISTOYLATION AT GLY-2, CLEAVAGE OF INITIATOR METHIONINE, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=25255805; DOI=10.1038/ncomms5919; RA Thinon E., Serwa R.A., Broncel M., Brannigan J.A., Brassat U., RA Wright M.H., Heal W.P., Wilkinson A.J., Mann D.J., Tate E.W.; RT "Global profiling of co- and post-translationally N-myristoylated RT proteomes in human cells."; RL Nat. Commun. 5:4919-4919(2014). RN [13] RP VARIANT FCM GLN-21, AND CHARACTERIZATION OF VARIANT FCM GLN-21. RX PubMed=22926851; DOI=10.1002/ana.23666; RA Russell J.F., Steckley J.L., Coppola G., Hahn A.F., Howard M.A., RA Kornberg Z., Huang A., Mirsattari S.M., Merriman B., Klein E., RA Choi M., Lee H.Y., Kirk A., Nelson-Williams C., Gibson G., RA Baraban S.C., Lifton R.P., Geschwind D.H., Fu Y.H., Ptacek L.J.; RT "Familial cortical myoclonus with a mutation in NOL3."; RL Ann. Neurol. 72:175-183(2012). RN [14] RP VARIANT FCM THR-80. RX PubMed=25138476; DOI=10.1007/s00415-014-7463-z; RA Macerollo A., Mencacci N.E., Erro R., Cordivari C., Edwards M.J., RA Wood N.W., Bhatia K.P.; RT "Screening of mutations in NOL3 in a myoclonic syndromes series."; RL J. Neurol. 261:1830-1831(2014). CC -!- FUNCTION: Isoform 1: May be involved in RNA splicing. CC {ECO:0000269|PubMed:10196175}. CC -!- FUNCTION: Isoform 2: Functions as an apoptosis repressor that CC blocks multiple modes of cell death. Inhibits extrinsic apoptotic CC pathways through two different ways. Firstly by interacting with CC FAS and FADD upon FAS activation blocking death-inducing signaling CC complex (DISC) assembly (By similarity). Secondly by interacting CC with CASP8 in a mitochondria localization- and phosphorylation- CC dependent manner, limiting the amount of soluble CASP8 available CC for DISC-mediated activation (By similarity). Inhibits intrinsic CC apoptotic pathway in response to a wide range of stresses, through CC its interaction with BAX resulting in BAX inactivation, preventing CC mitochondrial dysfunction and release of pro-apoptotic factors CC (PubMed:15004034). Inhibits calcium-mediated cell death by CC functioning as a cytosolic calcium buffer, dissociating its CC interaction with CASP8 and maintaining calcium homeostasis CC (PubMed:15509781). Negatively regulates oxidative stress-induced CC apoptosis by phosphorylation-dependent suppression of the CC mitochondria-mediated intrinsic pathway, by blocking CASP2 CC activation and BAX translocation (By similarity). Negatively CC regulates hypoxia-induced apoptosis in part by inhibiting the CC release of cytochrome c from mitochondria in a caspase-independent CC manner (By similarity). Also inhibits TNF-induced necrosis by CC preventing TNF-signaling pathway through TNFRSF1A interaction CC abrogating the recruitment of RIPK1 to complex I (By similarity). CC Finally through its role as apoptosis repressor, promotes vascular CC remodeling through inhibition of apoptosis and stimulation of CC proliferation, in response to hypoxia (By similarity). Inhibits CC too myoblast differentiation through caspase inhibition (By CC similarity). {ECO:0000250|UniProtKB:Q62881, CC ECO:0000250|UniProtKB:Q9D1X0, ECO:0000269|PubMed:15004034, CC ECO:0000269|PubMed:15509781}. CC -!- SUBUNIT: Oligomerizes (via CARD doamin). Interacts (via CARD CC domain) with CASP2; inhibits CASP2 activity in a phosphorylation- CC dependent manner. Interacts with CASP8; decreases CASP8 activity CC in a mitochondria localization- and phosphorylation-dependent CC manner and this interaction is dissociated by calcium. Interacts CC with TFPT; translocates NOL3 into the nucleus and negatively CC regulated TFPT-induced cell death (By similarity). Interacts CC directly (via CARD domain) with FAS and FADD (via DED domain); CC inhibits death-inducing signaling complex death-inducing signaling CC complex (DISC) assembly by inhibiting the increase in FAS-FADD CC binding induced by FAS activation (By similarity). Interacts (via CC CARD domain) with BAX (via a C-terminal 33 residues); inhibits BAX CC activation and translocation and consequently cytochrome c release CC from mitochondria. Interacts with PPM1G; may dephosphorylate NOL3 CC (By similarity). Interacts (via CARD domain) with BBC3 (via BH3 CC domain); preventing the association of BBC3 with BCL2 and CC resulting in activation of CASP8 (By similarity). Interacts (via CC CARD domain) with BAD(via BH3 domain); preventing the association CC of BAD with BCL2 (By similarity). Interacts directly (via CARD CC domain) with TNFRSF1A; inhibits TNF-signaling pathway (By CC similarity). Isoform 1 binds to SFRS9/SRp30C. CC {ECO:0000250|UniProtKB:Q62881, ECO:0000250|UniProtKB:Q9D1X0, CC ECO:0000269|PubMed:10196175, ECO:0000269|PubMed:15004034, CC ECO:0000269|PubMed:15509781, ECO:0000269|PubMed:9560245}. CC -!- INTERACTION: CC Self; NbExp=2; IntAct=EBI-740992, EBI-740992; CC Q14790:CASP8; NbExp=3; IntAct=EBI-740992, EBI-78060; CC Q9BSI4:TINF2; NbExp=2; IntAct=EBI-740992, EBI-717399; CC P04637:TP53; NbExp=3; IntAct=EBI-740992, EBI-366083; CC -!- SUBCELLULAR LOCATION: Isoform 1: Nucleus, nucleolus CC {ECO:0000269|PubMed:10196175}. Note=The SR-rich C-terminus CC mediates nuclear localization. {ECO:0000269|PubMed:10196175}. CC -!- SUBCELLULAR LOCATION: Isoform 3: Cytoplasm {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: Isoform 2: Cytoplasm CC {ECO:0000269|PubMed:10196175}. Mitochondrion CC {ECO:0000250|UniProtKB:Q62881}. Sarcoplasmic reticulum CC {ECO:0000250|UniProtKB:Q62881}. Membrane {ECO:0000305}; Lipid- CC anchor {ECO:0000305}. Note=Phosphorylation at Thr-149 results in CC translocation to mitochondria. Colocalized with mitochondria in CC response to oxidative stress. {ECO:0000250|UniProtKB:Q62881}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=2 {ECO:0000305}; Synonyms=Myp {ECO:0000303|PubMed:10196175}; CC IsoId=O60936-2; Sequence=Displayed; CC Name=1 {ECO:0000305}; Synonyms=Nop30 CC {ECO:0000303|PubMed:10196175}; CC IsoId=O60936-1; Sequence=VSP_057515; CC Name=3 {ECO:0000305}; CC IsoId=O60936-3; Sequence=VSP_054607; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Highly expressed in heart and skeletal muscle. CC Detected at low levels in placenta, liver, kidney and pancreas. CC -!- INDUCTION: Protein expression decreases in hearts failure patients CC (PubMed:16505176) and in response to oxidative stress CC (PubMed:17142452). {ECO:0000269|PubMed:16505176, CC ECO:0000269|PubMed:17142452}. CC -!- DOMAIN: CARD is critical for both extrinsic and intrinsic CC apoptotic pathways (By similarity). CARD domain mediates a CC protective effect against myocardial ischemia/reperfusion, CC oxidative stress and TNF-induced necrosis (PubMed:15004034) (By CC similarity). The calcium binding domain plays a protective role in CC calcium-mediated cell death (PubMed:15509781). CC {ECO:0000250|UniProtKB:O60936, ECO:0000250|UniProtKB:Q62881, CC ECO:0000269|PubMed:15004034, ECO:0000269|PubMed:15509781}. CC -!- PTM: Phosphorylation at Thr-149 is required for its antiapoptotic CC effect by blocking death-inducing signaling complex death-inducing CC signaling complex (DISC) activity through the control of CC interaction with CASP8. Phosphorylation at Thr-149 results in CC translocation to mitochondria and this translocation enables the CC binding to CASP8. Dephosphorylated at Thr-149 by calcineurin; CC doesn't inhibit the association between FADD and CASP8 and the CC consequent apoptosis. {ECO:0000250|UniProtKB:Q62881}. CC -!- PTM: Polyubiquitinated by MDM2; promoting proteasomal-dependent CC degradation in response to apoptotic stimuli. CC {ECO:0000250|UniProtKB:Q62881, ECO:0000269|PubMed:17142452}. CC -!- DISEASE: Myoclonus, familial cortical (FCM) [MIM:614937]: An CC autosomal dominant neurologic condition characterized by adult CC onset of cortical myoclonus manifest as involuntary jerks or CC movements affecting the face and limbs. Affected individuals can CC also experience falls without seizure activity or loss of CC consciousness. {ECO:0000269|PubMed:22926851, CC ECO:0000269|PubMed:25138476}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/NOL3ID41552ch16q22.html"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AF043244; AAC34993.1; -; mRNA. DR EMBL; AF064598; AAC18590.1; -; Genomic_DNA. DR EMBL; AF064598; AAC18591.1; -; Genomic_DNA. DR EMBL; AF064599; AAC18593.1; -; mRNA. DR EMBL; AF064600; AAC18594.1; -; mRNA. DR EMBL; AK294145; BAG57471.1; -; mRNA. DR EMBL; AC074143; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471092; EAW83087.1; -; Genomic_DNA. DR EMBL; BC012798; AAH12798.1; -; mRNA. DR CCDS; CCDS42176.1; -. [O60936-2] DR CCDS; CCDS58473.1; -. [O60936-1] DR CCDS; CCDS61960.1; -. [O60936-3] DR RefSeq; NP_001171986.1; NM_001185057.2. [O60936-1] DR RefSeq; NP_001263236.1; NM_001276307.1. [O60936-2] DR RefSeq; NP_001263238.1; NM_001276309.1. [O60936-2] DR RefSeq; NP_001263240.1; NM_001276311.1. DR RefSeq; NP_001263241.1; NM_001276312.1. [O60936-2] DR RefSeq; NP_001263248.1; NM_001276319.1. [O60936-3] DR RefSeq; NP_003937.1; NM_003946.6. [O60936-2] DR RefSeq; XP_016879332.1; XM_017023843.1. [O60936-3] DR UniGene; Hs.513667; -. DR PDB; 4UZ0; X-ray; 2.40 A; A/B=1-95. DR PDBsum; 4UZ0; -. DR ProteinModelPortal; O60936; -. DR SMR; O60936; -. DR BioGrid; 114477; 38. DR DIP; DIP-29940N; -. DR IntAct; O60936; 13. DR STRING; 9606.ENSP00000268605; -. DR iPTMnet; O60936; -. DR PhosphoSitePlus; O60936; -. DR EPD; O60936; -. DR PaxDb; O60936; -. DR PeptideAtlas; O60936; -. DR PRIDE; O60936; -. DR ProteomicsDB; 49679; -. DR ProteomicsDB; 49680; -. [O60936-2] DR DNASU; 8996; -. DR Ensembl; ENST00000268605; ENSP00000268605; ENSG00000140939. [O60936-2] DR Ensembl; ENST00000564053; ENSP00000457243; ENSG00000140939. [O60936-3] DR Ensembl; ENST00000568146; ENSP00000454598; ENSG00000140939. [O60936-1] DR GeneID; 8996; -. DR KEGG; hsa:8996; -. DR UCSC; uc010vjd.4; human. [O60936-2] DR CTD; 8996; -. DR DisGeNET; 8996; -. DR EuPathDB; HostDB:ENSG00000140939.14; -. DR GeneCards; NOL3; -. DR HGNC; HGNC:7869; NOL3. DR HPA; CAB009208; -. DR MalaCards; NOL3; -. DR MIM; 605235; gene. DR MIM; 614937; phenotype. DR neXtProt; NX_O60936; -. DR OpenTargets; ENSG00000140939; -. DR Orphanet; 319189; Familial cortical myoclonus. DR PharmGKB; PA31673; -. DR eggNOG; ENOG410J0R1; Eukaryota. DR eggNOG; ENOG4111BHK; LUCA. DR GeneTree; ENSGT00510000049353; -. DR HOGENOM; HOG000113820; -. DR InParanoid; O60936; -. DR OMA; DWQHVGT; -. DR OrthoDB; EOG091G0U8K; -. DR PhylomeDB; O60936; -. DR TreeFam; TF336957; -. DR ChiTaRS; NOL3; human. DR GeneWiki; NOL3; -. DR GenomeRNAi; 8996; -. DR PRO; PR:O60936; -. DR Proteomes; UP000005640; Chromosome 16. DR Bgee; ENSG00000140939; -. DR CleanEx; HS_ARC; -. DR CleanEx; HS_NOL3; -. DR ExpressionAtlas; O60936; baseline and differential. DR Genevisible; O60936; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:ProtInc. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0016529; C:sarcoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0005509; F:calcium ion binding; IMP:UniProtKB. DR GO; GO:0089720; F:caspase binding; IPI:UniProtKB. DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0035877; F:death effector domain binding; IEA:Ensembl. DR GO; GO:0005123; F:death receptor binding; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0003723; F:RNA binding; TAS:ProtInc. DR GO; GO:0001974; P:blood vessel remodeling; IEA:Ensembl. DR GO; GO:0010659; P:cardiac muscle cell apoptotic process; IEA:Ensembl. DR GO; GO:1990001; P:inhibition of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0006376; P:mRNA splice site selection; IDA:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IEA:Ensembl. DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IDA:UniProtKB. DR GO; GO:1903298; P:negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway; ISS:UniProtKB. DR GO; GO:1902109; P:negative regulation of mitochondrial membrane permeability involved in apoptotic process; IEA:Ensembl. DR GO; GO:0014736; P:negative regulation of muscle atrophy; IEA:Ensembl. DR GO; GO:0060547; P:negative regulation of necrotic cell death; IEA:Ensembl. DR GO; GO:1902176; P:negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; IDA:UniProtKB. DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; IDA:UniProtKB. DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0051259; P:protein complex oligomerization; IDA:UniProtKB. DR GO; GO:1901222; P:regulation of NIK/NF-kappaB signaling; IEA:Ensembl. DR GO; GO:0014808; P:release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0014876; P:response to injury involved in regulation of muscle adaptation; IEA:Ensembl. DR GO; GO:0002931; P:response to ischemia; IEA:Ensembl. DR GO; GO:0008380; P:RNA splicing; TAS:ProtInc. DR InterPro; IPR001315; CARD. DR InterPro; IPR011029; DEATH-like_dom_sf. DR Pfam; PF00619; CARD; 1. DR SMART; SM00114; CARD; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR PROSITE; PS50209; CARD; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; Calcium; KW Complete proteome; Cytoplasm; Disease mutation; Lipoprotein; Membrane; KW Metal-binding; Mitochondrion; mRNA processing; mRNA splicing; KW Myristate; Nucleus; Phosphoprotein; Reference proteome; KW Sarcoplasmic reticulum; Ubl conjugation. FT INIT_MET 1 1 Removed. {ECO:0000269|PubMed:25255805}. FT CHAIN 2 208 Nucleolar protein 3. FT /FTId=PRO_0000144099. FT DOMAIN 4 95 CARD. {ECO:0000255|PROSITE- FT ProRule:PRU00046}. FT CA_BIND 99 208 {ECO:0000269|PubMed:15509781}. FT MOD_RES 149 149 Phosphothreonine; by CK2. FT {ECO:0000250|UniProtKB:Q62881}. FT LIPID 2 2 N-myristoyl glycine. FT {ECO:0000269|PubMed:25255805}. FT VAR_SEQ 1 1 M -> MPVLGKAGEERRATADAWGQKEEPEEETGQSVWRGR FT RTPSSPCWPPGPVLAEPSGGWDRAPTM (in isoform FT 3). {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_054607. FT VAR_SEQ 96 208 VGPGYRDRSYDPPCPGHWTPEAPGSGTTCPGLPRASDPDEA FT GGPEGSEAVQSGTPEEPEPELEAEASKEAEPEPEPEPELEP FT EAEAEPEPELEPEPDPEPEPDFEERDESEDS -> ATGTAA FT MTLHAQATGRRRHPARGPHAPGCPELQTLTRPGALRAPRRC FT NPGPRRSQSQSWKLRPLKRLNRSRSQSQSWNPRLKQNQSRN FT WSQNRTQSPSPTSRKGTSPKIPEGQSSDRRCPAHAG (in FT isoform 1). FT {ECO:0000303|PubMed:10196175}. FT /FTId=VSP_057515. FT VARIANT 21 21 E -> Q (in FCM; the mutation may alter FT post-translational modification of the FT protein; dbSNP:rs397514600). FT {ECO:0000269|PubMed:22926851}. FT /FTId=VAR_069731. FT VARIANT 80 80 A -> T (in FCM; dbSNP:rs780601409). FT {ECO:0000269|PubMed:25138476}. FT /FTId=VAR_072644. FT MUTAGEN 17 17 K->R: Abolished ubiquitination in FT response to an apoptotic stimulus; when FT associated with R-68 and R-163. FT {ECO:0000269|PubMed:17142452}. FT MUTAGEN 31 31 L->F: Did not reduce creatine kinase FT release or infarct size after myocardial FT ischemia/reperfusion. Causes loss of FT mitochondrial membrane potential and FT nuclear condensation. Failes to prevent FT the increase in Bax. Interacts with BAX. FT {ECO:0000269|PubMed:15004034}. FT MUTAGEN 68 68 K->R: Abolished ubiquitination in FT response to an apoptotic stimulus; when FT associated with R-17 and R-163. FT {ECO:0000269|PubMed:17142452}. FT MUTAGEN 163 163 K->R: Abolished ubiquitination in FT response to an apoptotic stimulus; when FT associated with R-17 and R-68. FT {ECO:0000269|PubMed:17142452}. FT HELIX 8 23 {ECO:0000244|PDB:4UZ0}. FT HELIX 27 36 {ECO:0000244|PDB:4UZ0}. FT HELIX 42 50 {ECO:0000244|PDB:4UZ0}. FT HELIX 54 68 {ECO:0000244|PDB:4UZ0}. FT HELIX 70 84 {ECO:0000244|PDB:4UZ0}. SQ SEQUENCE 208 AA; 22629 MW; 239EF1A143EF6168 CRC64; MGNAQERPSE TIDRERKRLV ETLQADSGLL LDALLARGVL TGPEYEALDA LPDAERRVRR LLLLVQGKGE AACQELLRCA QRTAGAPDPA WDWQHVGPGY RDRSYDPPCP GHWTPEAPGS GTTCPGLPRA SDPDEAGGPE GSEAVQSGTP EEPEPELEAE ASKEAEPEPE PEPELEPEAE AEPEPELEPE PDPEPEPDFE ERDESEDS // ID RIPK2_HUMAN Reviewed; 540 AA. AC O43353; B7Z748; Q6UWF0; DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 2. DT 18-JUL-2018, entry version 198. DE RecName: Full=Receptor-interacting serine/threonine-protein kinase 2; DE EC=2.7.11.1; DE AltName: Full=CARD-containing interleukin-1 beta-converting enzyme-associated kinase; DE Short=CARD-containing IL-1 beta ICE-kinase; DE AltName: Full=RIP-like-interacting CLARP kinase; DE AltName: Full=Receptor-interacting protein 2; DE Short=RIP-2; DE AltName: Full=Tyrosine-protein kinase RIPK2; DE EC=2.7.10.2; GN Name=RIPK2; Synonyms=CARDIAK, RICK, RIP2; GN ORFNames=UNQ277/PRO314/PRO34092; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND MUTAGENESIS OF LYS-47. RX PubMed=9575181; DOI=10.1074/jbc.273.20.12296; RA Inohara N., del Peso L., Koseki T., Chen S., Nunez G.; RT "RICK, a novel protein kinase containing a caspase recruitment domain, RT interacts with CLARP and regulates CD95-mediated apoptosis."; RL J. Biol. Chem. 273:12296-12300(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND MUTAGENESIS OF LYS-47. RC TISSUE=Endothelial cell; RX PubMed=9642260; DOI=10.1074/jbc.273.27.16968; RA McCarthy J.V., Ni J., Dixit V.M.; RT "RIP2 is a novel NF-kappaB-activating and cell death-inducing RT kinase."; RL J. Biol. Chem. 273:16968-16975(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND MUTAGENESIS OF ASP-146. RC TISSUE=Pancreatic adenocarcinoma; RX PubMed=9705938; DOI=10.1016/S0960-9822(07)00352-1; RA Thome M., Hofmann K., Burns K., Martinon F., Bodmer J.-L., RA Mattmann C., Tschopp J.; RT "Identification of CARDIAK, a RIP-like kinase that associates with RT caspase-1."; RL Curr. Biol. 8:885-888(1998). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., RA Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale RT effort to identify novel human secreted and transmembrane proteins: a RT bioinformatics assessment."; RL Genome Res. 13:2265-2270(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Synovium; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., RA Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., RA Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., RA Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T., RA Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., RA DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., RA Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., RA Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., RA O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., RA Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., RA Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., RA Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., RA Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., RA Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP FUNCTION. RX PubMed=14638696; DOI=10.1074/jbc.C300460200; RA Ruefli-Brasse A.A., Lee W.P., Hurst S., Dixit V.M.; RT "Rip2 participates in Bcl10 signaling and T-cell receptor-mediated NF- RT kappaB activation."; RL J. Biol. Chem. 279:1570-1574(2004). RN [9] RP PHOSPHORYLATION AT SER-176. RX PubMed=16824733; DOI=10.1016/j.cellsig.2006.05.005; RA Dorsch M., Wang A., Cheng H., Lu C., Bielecki A., Charron K., RA Clauser K., Ren H., Polakiewicz R.D., Parsons T., Li P., Ocain T., RA Xu Y.; RT "Identification of a regulatory autophosphorylation site in the RT serine-threonine kinase RIP2."; RL Cell. Signal. 18:2223-2229(2006). RN [10] RP FUNCTION, INTERACTION WITH NOD1, AND MUTAGENESIS OF ARG-444; ARG-483 RP AND ARG-488. RX PubMed=17054981; DOI=10.1016/j.jmb.2006.09.067; RA Manon F., Favier A., Nunez G., Simorre J.P., Cusack S.; RT "Solution structure of NOD1 CARD and mutational analysis of its RT interaction with the CARD of downstream kinase RICK."; RL J. Mol. Biol. 365:160-174(2007). RN [11] RP INTERACTION WITH MAP3K4. RX PubMed=18775659; DOI=10.1016/j.cub.2008.07.084; RA Clark N.M., Marinis J.M., Cobb B.A., Abbott D.W.; RT "MEKK4 sequesters RIP2 to dictate NOD2 signal specificity."; RL Curr. Biol. 18:1402-1408(2008). RN [12] RP INTERACTION WITH IKBKG/NEMO AND MAP3K7/TAK1, FUNCTION, UBIQUITINATION RP AT LYS-209, AND MUTAGENESIS OF LYS-209. RX PubMed=18079694; DOI=10.1038/sj.emboj.7601962; RA Hasegawa M., Fujimoto Y., Lucas P.C., Nakano H., Fukase K., Nunez G., RA Inohara N.; RT "A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF- RT kappaB activation."; RL EMBO J. 27:373-383(2008). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-363; SER-527 AND RP SER-539, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-531, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [15] RP UBIQUITINATION BY ITCH, AND INTERACTION WITH NOD2. RX PubMed=19592251; DOI=10.1016/j.cub.2009.06.038; RA Tao M., Scacheri P.C., Marinis J.M., Harhaj E.W., Matesic L.E., RA Abbott D.W.; RT "ITCH K63-ubiquitinates the NOD2 binding protein, RIP2, to influence RT inflammatory signaling pathways."; RL Curr. Biol. 19:1255-1263(2009). RN [16] RP UBIQUITINATION BY BIRC2 AND BIRC3. RX PubMed=19464198; DOI=10.1016/j.immuni.2009.04.011; RA Bertrand M.J., Doiron K., Labbe K., Korneluk R.G., Barker P.A., RA Saleh M.; RT "Cellular inhibitors of apoptosis cIAP1 and cIAP2 are required for RT innate immunity signaling by the pattern recognition receptors NOD1 RT and NOD2."; RL Immunity 30:789-801(2009). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168; SER-363; SER-393; RP SER-527 AND SER-539, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE RP SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [18] RP FUNCTION, PHOSPHORYLATION AT TYR-474, AND MUTAGENESIS OF TYR-474. RX PubMed=21123652; DOI=10.1101/gad.1964410; RA Tigno-Aranjuez J.T., Asara J.M., Abbott D.W.; RT "Inhibition of RIP2's tyrosine kinase activity limits NOD2-driven RT cytokine responses."; RL Genes Dev. 24:2666-2677(2010). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-529, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [21] RP UBIQUITINATION BY BIRC2/C-IAP1 AND BIRC3/C-IAP2, AND INTERACTION WITH RP BIRC2/C-IAP1; BIRC3/C-IAP2 AND XIAP/BIRC4. RX PubMed=21931591; DOI=10.1371/journal.pone.0022356; RA Bertrand M.J., Lippens S., Staes A., Gilbert B., Roelandt R., RA De Medts J., Gevaert K., Declercq W., Vandenabeele P.; RT "cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin RT chains to receptor interacting proteins kinases 1 to 4 (RIP1-4)."; RL PLoS ONE 6:E22356-E22356(2011). RN [22] RP INTERACTION WITH NLRP10. RX PubMed=22672233; DOI=10.1111/j.1462-5822.2012.01822.x; RA Lautz K., Damm A., Menning M., Wenger J., Adam A.C., Zigrino P., RA Kremmer E., Kufer T.A.; RT "NLRP10 enhances Shigella-induced pro-inflammatory responses."; RL Cell. Microbiol. 14:1568-1583(2012). RN [23] RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH ARHGEF2 AND NOD2, RP INTERACTION WITH ARHGEF2 AND NOD2, AND PHOSPHORYLATION AT TYR-381. RX PubMed=21887730; DOI=10.1002/ibd.21851; RA Zhao Y., Alonso C., Ballester I., Song J.H., Chang S.Y., Guleng B., RA Arihiro S., Murray P.J., Xavier R., Kobayashi K.S., Reinecker H.C.; RT "Control of NOD2 and Rip2-dependent innate immune activation by GEF- RT H1."; RL Inflamm. Bowel Dis. 18:603-612(2012). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-363; SER-527; SER-529 RP AND SER-531, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [25] RP UBIQUITINATION, AND DEUBIQUITINATION. RX PubMed=23806334; DOI=10.1016/j.molcel.2013.06.004; RA Fiil B.K., Damgaard R.B., Wagner S.A., Keusekotten K., Fritsch M., RA Bekker-Jensen S., Mailand N., Choudhary C., Komander D., RA Gyrd-Hansen M.; RT "OTULIN restricts Met1-linked ubiquitination to control innate immune RT signaling."; RL Mol. Cell 50:818-830(2013). RN [26] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [27] RP INTERACTION WITH INAVA. RX PubMed=28436939; DOI=10.1172/JCI86282; RA Yan J., Hedl M., Abraham C.; RT "An inflammatory bowel disease-risk variant in INAVA decreases pattern RT recognition receptor-induced outcomes."; RL J. Clin. Invest. 127:2192-2205(2017). RN [28] RP VARIANTS [LARGE SCALE ANALYSIS] THR-259; VAL-268 AND ASN-313. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Serine/threonine/tyrosine kinase that plays an essential CC role in modulation of innate and adaptive immune responses. Upon CC stimulation by bacterial peptidoglycans, NOD1 and NOD2 are CC activated, oligomerize and recruit RIPK2 through CARD-CARD CC domains. Contributes to the tyrosine phosphorylation of the CC guanine exchange factor ARHGEF2 through Src tyrosine kinase CC leading to NF-kappaB activation by NOD2. Once recruited, RIPK2 CC autophosphorylates and undergoes 'Lys-63'-linked CC polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3. CC The polyubiquitinated protein mediates the recruitment of CC MAP3K7/TAK1 to IKBKG/NEMO and induces 'Lys-63'-linked CC polyubiquitination of IKBKG/NEMO and subsequent activation of CC IKBKB/IKKB. In turn, NF-kappa-B is released from NF-kappa-B CC inhibitors and translocates into the nucleus where it activates CC the transcription of hundreds of genes involved in immune CC response, growth control, or protection against apoptosis. Plays CC also a role during engagement of the T-cell receptor (TCR) in CC promoting BCL10 phosphorylation and subsequent NF-kappa-B CC activation. {ECO:0000269|PubMed:14638696, CC ECO:0000269|PubMed:17054981, ECO:0000269|PubMed:18079694, CC ECO:0000269|PubMed:21123652, ECO:0000269|PubMed:21887730}. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a CC [protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE- CC ProRule:PRU10027}. CC -!- SUBUNIT: Found in a signaling complex consisting of at least CC ARHGEF2, NOD2 and RIPK2. Interacts with ARHGEF2; the interaction CC mediates tyrosine phosphorylation of RIPK2 by Src kinase CSK. CC Binds to CFLAR/CLARP and CASP1 via their CARD domains. Binds to CC BIRC3/c-IAP1 and BIRC2/c-IAP2, TRAF1, TRAF2, TRAF5 and TRAF6. May CC be a component of both the TNFRSF1A and TNRFSF5/CD40 receptor CC complex. Interacts with NOD1. Interacts (via CARD domain) with CC NOD2 (via CARD domain). Interacts with MAP3K4; this interaction CC sequesters RIPK2 from the NOD2 signaling pathway. Interacts with CC IKBKG/NEMO. The polyubiquitinated protein interacts with CC MAP3K7/TAK1. Interacts with XIAP/BIRC4. Interacts with NLRP10. CC Interacts with CARD9. Interacts with INAVA; the interaction takes CC place upon PRR stimulation (PubMed:28436939). CC {ECO:0000269|PubMed:17054981, ECO:0000269|PubMed:18079694, CC ECO:0000269|PubMed:18775659, ECO:0000269|PubMed:19592251, CC ECO:0000269|PubMed:21887730, ECO:0000269|PubMed:21931591, CC ECO:0000269|PubMed:22672233, ECO:0000269|PubMed:28436939}. CC -!- INTERACTION: CC Self; NbExp=4; IntAct=EBI-358522, EBI-358522; CC Q13490:BIRC2; NbExp=3; IntAct=EBI-358522, EBI-514538; CC Q13489:BIRC3; NbExp=3; IntAct=EBI-358522, EBI-517709; CC Q9BX69:CARD6; NbExp=2; IntAct=EBI-358522, EBI-14405242; CC Q7Z434:MAVS; NbExp=3; IntAct=EBI-358522, EBI-995373; CC Q9Y239:NOD1; NbExp=2; IntAct=EBI-358522, EBI-1051262; CC Q9HC29:NOD2; NbExp=3; IntAct=EBI-358522, EBI-7445625; CC Q12933:TRAF2; NbExp=2; IntAct=EBI-358522, EBI-355744; CC Q13114:TRAF3; NbExp=5; IntAct=EBI-358522, EBI-357631; CC P98170:XIAP; NbExp=12; IntAct=EBI-358522, EBI-517127; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O43353-1; Sequence=Displayed; CC Name=2; CC IsoId=O43353-2; Sequence=VSP_013266; CC -!- TISSUE SPECIFICITY: Detected in heart, brain, placenta, lung, CC peripheral blood leukocytes, spleen, kidney, testis, prostate, CC pancreas and lymph node. CC -!- DOMAIN: Contains an N-terminal kinase domain and a C-terminal CC caspase activation and recruitment domain (CARD) that mediates the CC recruitment of CARD-containing proteins. CC -!- PTM: Autophosphorylated. Autophosphorylation at Tyr-474 is CC necessary for effective NOD2 signaling. Phosphorylated. CC Phosphorylation at Tyr-381 by Src kinase CSK occurs in a ARHGEF2- CC dependent manner and is required for NOD2-dependent innate immune CC activation. {ECO:0000269|PubMed:16824733, CC ECO:0000269|PubMed:21123652, ECO:0000269|PubMed:21887730}. CC -!- PTM: Ubiquitinated on Lys-209; undergoes 'Lys-63'-linked CC polyubiquitination catalyzed by ITCH. Polyubiquitinated with 'Lys- CC 48' and 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, CC leading to activation of NF-kappa-B. Also undergoes 'Met-1'-linked CC polyubiquitination; the head-to-tail linear polyubiquitination is CC mediated by the LUBAC complex in response to NOD2 stimulation. CC Linear polyubiquitination is restricted by FAM105B/otulin, CC probably to limit NOD2-dependent proinflammatory signaling CC activation of NF-kappa-B. {ECO:0000269|PubMed:18079694, CC ECO:0000269|PubMed:19464198, ECO:0000269|PubMed:19592251, CC ECO:0000269|PubMed:21931591, ECO:0000269|PubMed:23806334}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr CC protein kinase family. {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AF027706; AAC34970.1; -; mRNA. DR EMBL; AF078530; AAC27722.1; -; mRNA. DR EMBL; AF064824; AAC25668.1; -; mRNA. DR EMBL; AY358813; AAQ89172.1; -; mRNA. DR EMBL; AY358814; AAQ89173.1; -; mRNA. DR EMBL; AK301448; BAH13484.1; -; mRNA. DR EMBL; AC004003; AAC24561.1; -; Genomic_DNA. DR EMBL; AF117829; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC004553; AAH04553.1; -; mRNA. DR CCDS; CCDS6247.1; -. [O43353-1] DR RefSeq; NP_003812.1; NM_003821.5. [O43353-1] DR RefSeq; XP_005251149.1; XM_005251092.3. [O43353-2] DR UniGene; Hs.103755; -. DR PDB; 2N7Z; NMR; -; A=434-539. DR PDB; 2N83; NMR; -; B=434-539. DR PDB; 4C8B; X-ray; 2.75 A; A/B=8-317. DR PDB; 5AR2; X-ray; 2.44 A; A/B=1-310. DR PDB; 5AR3; X-ray; 3.23 A; A/B=1-310. DR PDB; 5AR4; X-ray; 2.70 A; A/B=1-310. DR PDB; 5AR5; X-ray; 2.66 A; A/B=1-310. DR PDB; 5AR7; X-ray; 2.71 A; A/B=1-310. DR PDB; 5AR8; X-ray; 2.79 A; A/B=1-310. DR PDB; 5J79; X-ray; 2.69 A; A/B=1-310. DR PDB; 5J7B; X-ray; 2.53 A; A/B=1-310. DR PDB; 5NG0; X-ray; 2.00 A; A/B=1-300. DR PDB; 5NG2; X-ray; 2.80 A; A/B=1-300. DR PDB; 5NG3; X-ray; 2.60 A; A/B/C/D=1-300. DR PDB; 5W5J; X-ray; 2.85 A; A/B=2-311. DR PDB; 5W5O; X-ray; 2.89 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=2-311. DR PDB; 6ES0; X-ray; 2.38 A; A/B=3-317. DR PDB; 6FU5; X-ray; 3.26 A; A/B=3-317. DR PDBsum; 2N7Z; -. DR PDBsum; 2N83; -. DR PDBsum; 4C8B; -. DR PDBsum; 5AR2; -. DR PDBsum; 5AR3; -. DR PDBsum; 5AR4; -. DR PDBsum; 5AR5; -. DR PDBsum; 5AR7; -. DR PDBsum; 5AR8; -. DR PDBsum; 5J79; -. DR PDBsum; 5J7B; -. DR PDBsum; 5NG0; -. DR PDBsum; 5NG2; -. DR PDBsum; 5NG3; -. DR PDBsum; 5W5J; -. DR PDBsum; 5W5O; -. DR PDBsum; 6ES0; -. DR PDBsum; 6FU5; -. DR ProteinModelPortal; O43353; -. DR SMR; O43353; -. DR BioGrid; 114300; 47. DR DIP; DIP-27518N; -. DR IntAct; O43353; 58. DR MINT; O43353; -. DR STRING; 9606.ENSP00000220751; -. DR BindingDB; O43353; -. DR ChEMBL; CHEMBL5014; -. DR GuidetoPHARMACOLOGY; 2190; -. DR iPTMnet; O43353; -. DR PhosphoSitePlus; O43353; -. DR BioMuta; RIPK2; -. DR EPD; O43353; -. DR MaxQB; O43353; -. DR PaxDb; O43353; -. DR PeptideAtlas; O43353; -. DR PRIDE; O43353; -. DR ProteomicsDB; 48908; -. DR ProteomicsDB; 48909; -. [O43353-2] DR DNASU; 8767; -. DR Ensembl; ENST00000220751; ENSP00000220751; ENSG00000104312. [O43353-1] DR GeneID; 8767; -. DR KEGG; hsa:8767; -. DR UCSC; uc003yee.4; human. [O43353-1] DR CTD; 8767; -. DR DisGeNET; 8767; -. DR EuPathDB; HostDB:ENSG00000104312.7; -. DR GeneCards; RIPK2; -. DR HGNC; HGNC:10020; RIPK2. DR HPA; HPA015273; -. DR HPA; HPA016499; -. DR MIM; 603455; gene. DR neXtProt; NX_O43353; -. DR OpenTargets; ENSG00000104312; -. DR PharmGKB; PA34395; -. DR eggNOG; KOG0192; Eukaryota. DR eggNOG; COG0515; LUCA. DR GeneTree; ENSGT00550000074536; -. DR HOGENOM; HOG000136856; -. DR HOVERGEN; HBG054242; -. DR InParanoid; O43353; -. DR KO; K08846; -. DR OMA; QWIQSKR; -. DR OrthoDB; EOG091G0505; -. DR PhylomeDB; O43353; -. DR TreeFam; TF106506; -. DR BRENDA; 2.7.10.2; 2681. DR Reactome; R-HSA-168638; NOD1/2 Signaling Pathway. DR Reactome; R-HSA-202424; Downstream TCR signaling. DR Reactome; R-HSA-209543; p75NTR recruits signalling complexes. DR Reactome; R-HSA-445989; TAK1 activates NFkB by phosphorylation and activation of IKKs complex. DR Reactome; R-HSA-450302; activated TAK1 mediates p38 MAPK activation. DR Reactome; R-HSA-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1. DR Reactome; R-HSA-5689896; Ovarian tumor domain proteases. DR Reactome; R-HSA-9020702; Interleukin-1 signaling. DR SignaLink; O43353; -. DR SIGNOR; O43353; -. DR ChiTaRS; RIPK2; human. DR GeneWiki; RIPK2; -. DR GenomeRNAi; 8767; -. DR PRO; PR:O43353; -. DR Proteomes; UP000005640; Chromosome 8. DR Bgee; ENSG00000104312; -. DR CleanEx; HS_RIPK2; -. DR ExpressionAtlas; O43353; baseline and differential. DR Genevisible; O43353; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005856; C:cytoskeleton; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0031982; C:vesicle; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0050700; F:CARD domain binding; IDA:MGI. DR GO; GO:0089720; F:caspase binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0030274; F:LIM domain binding; IPI:UniProtKB. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:UniProtKB-EC. DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central. DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB. DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; IDA:UniProtKB. DR GO; GO:0000187; P:activation of MAPK activity; TAS:Reactome. DR GO; GO:0002250; P:adaptive immune response; ISS:UniProtKB. DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc. DR GO; GO:0071223; P:cellular response to lipoteichoic acid; IEA:Ensembl. DR GO; GO:0071225; P:cellular response to muramyl dipeptide; IDA:UniProtKB. DR GO; GO:0071224; P:cellular response to peptidoglycan; IEA:Ensembl. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IEA:Ensembl. DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB. DR GO; GO:0006954; P:inflammatory response; TAS:ProtInc. DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB. DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; TAS:Reactome. DR GO; GO:0007254; P:JNK cascade; TAS:Reactome. DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0000165; P:MAPK cascade; IBA:GO_Central. DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:Reactome. DR GO; GO:0070427; P:nucleotide-binding oligomerization domain containing 1 signaling pathway; IEA:Ensembl. DR GO; GO:0070431; P:nucleotide-binding oligomerization domain containing 2 signaling pathway; IDA:UniProtKB. DR GO; GO:0070423; P:nucleotide-binding oligomerization domain containing signaling pathway; TAS:Reactome. DR GO; GO:0046641; P:positive regulation of alpha-beta T cell proliferation; IEA:Ensembl. DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl. DR GO; GO:0010942; P:positive regulation of cell death; IDA:UniProtKB. DR GO; GO:0032722; P:positive regulation of chemokine production; IEA:Ensembl. DR GO; GO:0001961; P:positive regulation of cytokine-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:MGI. DR GO; GO:0033091; P:positive regulation of immature T cell proliferation; IEA:Ensembl. DR GO; GO:0032727; P:positive regulation of interferon-alpha production; NAS:BHF-UCL. DR GO; GO:0032728; P:positive regulation of interferon-beta production; NAS:BHF-UCL. DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IEA:Ensembl. DR GO; GO:0050718; P:positive regulation of interleukin-1 beta secretion; IDA:UniProtKB. DR GO; GO:0032735; P:positive regulation of interleukin-12 production; NAS:BHF-UCL. DR GO; GO:0032743; P:positive regulation of interleukin-2 production; IEA:Ensembl. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl. DR GO; GO:0046330; P:positive regulation of JNK cascade; IEA:Ensembl. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:UniProtKB. DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IDA:UniProtKB. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:UniProtKB. DR GO; GO:0032092; P:positive regulation of protein binding; IMP:UniProtKB. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IMP:UniProtKB. DR GO; GO:0045627; P:positive regulation of T-helper 1 cell differentiation; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; NAS:BHF-UCL. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl. DR GO; GO:1904417; P:positive regulation of xenophagy; IEA:Ensembl. DR GO; GO:0043330; P:response to exogenous dsRNA; IEA:Ensembl. DR GO; GO:0070671; P:response to interleukin-12; IEA:Ensembl. DR GO; GO:0070673; P:response to interleukin-18; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0042098; P:T cell proliferation; IEA:Ensembl. DR GO; GO:0050852; P:T cell receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0034134; P:toll-like receptor 2 signaling pathway; IDA:MGI. DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IEA:Ensembl. DR InterPro; IPR001315; CARD. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017322; Rcpt-int_Ser/Thr_kinase-2. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR Pfam; PF00619; CARD; 1. DR Pfam; PF07714; Pkinase_Tyr; 1. DR PIRSF; PIRSF037921; STPK_RIP2; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR SUPFAM; SSF56112; SSF56112; 1. DR PROSITE; PS50209; CARD; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; Alternative splicing; Apoptosis; KW ATP-binding; Complete proteome; Cytoplasm; Immunity; Innate immunity; KW Isopeptide bond; Kinase; Nucleotide-binding; Phosphoprotein; KW Polymorphism; Reference proteome; Serine/threonine-protein kinase; KW Transferase; Ubl conjugation. FT CHAIN 1 540 Receptor-interacting serine/threonine- FT protein kinase 2. FT /FTId=PRO_0000086608. FT DOMAIN 18 294 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT DOMAIN 432 524 CARD. {ECO:0000255|PROSITE- FT ProRule:PRU00046}. FT NP_BIND 24 32 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT ACT_SITE 146 146 Proton acceptor. FT BINDING 47 47 ATP. FT MOD_RES 168 168 Phosphoserine. FT {ECO:0000244|PubMed:19369195}. FT MOD_RES 176 176 Phosphoserine; by autocatalysis. FT {ECO:0000269|PubMed:16824733}. FT MOD_RES 363 363 Phosphoserine. FT {ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:19369195, FT ECO:0000244|PubMed:23186163}. FT MOD_RES 381 381 Phosphotyrosine; by CSK. FT {ECO:0000269|PubMed:21887730}. FT MOD_RES 393 393 Phosphoserine. FT {ECO:0000244|PubMed:19369195}. FT MOD_RES 474 474 Phosphotyrosine; by autocatalysis. FT {ECO:0000269|PubMed:21123652}. FT MOD_RES 527 527 Phosphoserine. FT {ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:19369195, FT ECO:0000244|PubMed:23186163}. FT MOD_RES 529 529 Phosphoserine. FT {ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:23186163}. FT MOD_RES 531 531 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:23186163}. FT MOD_RES 539 539 Phosphoserine. FT {ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:19369195}. FT CROSSLNK 209 209 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000269|PubMed:18079694}. FT VAR_SEQ 1 137 Missing (in isoform 2). FT {ECO:0000303|PubMed:12975309, FT ECO:0000303|PubMed:14702039}. FT /FTId=VSP_013266. FT VARIANT 259 259 I -> T (in dbSNP:rs2230801). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_041045. FT VARIANT 268 268 L -> V (in dbSNP:rs35004667). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_041046. FT VARIANT 313 313 K -> N (in dbSNP:rs35395048). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_041047. FT MUTAGEN 47 47 K->A: Abolishes kinase activity. FT {ECO:0000269|PubMed:9575181, FT ECO:0000269|PubMed:9642260}. FT MUTAGEN 47 47 K->M: Reduces FAS-mediated apoptosis. FT {ECO:0000269|PubMed:9575181, FT ECO:0000269|PubMed:9642260}. FT MUTAGEN 146 146 D->N: Abolishes kinase activity. FT {ECO:0000269|PubMed:9705938}. FT MUTAGEN 209 209 K->R: Complete loss of FT polyubiquitination. FT {ECO:0000269|PubMed:18079694}. FT MUTAGEN 381 381 Y->A: Prevents phosphorylation. Reduces FT serine and threonine phosphorylation of FT ARHGEF2. FT MUTAGEN 444 444 R->E: Abolishes interaction with NOD1. FT {ECO:0000269|PubMed:17054981}. FT MUTAGEN 474 474 Y->F: Decreases interaction with NOD2. FT {ECO:0000269|PubMed:21123652}. FT MUTAGEN 483 483 R->E: Abolishes interaction with NOD1. FT {ECO:0000269|PubMed:17054981}. FT MUTAGEN 488 488 R->E: Abolishes interaction with NOD1. FT {ECO:0000269|PubMed:17054981}. FT CONFLICT 271 271 S -> G (in Ref. 5; BAH13484). FT {ECO:0000305}. FT CONFLICT 514 514 Q -> R (in Ref. 5; BAH13484). FT {ECO:0000305}. FT STRAND 7 9 {ECO:0000244|PDB:5NG0}. FT HELIX 15 17 {ECO:0000244|PDB:5NG0}. FT STRAND 18 26 {ECO:0000244|PDB:5NG0}. FT STRAND 31 37 {ECO:0000244|PDB:5NG0}. FT TURN 38 40 {ECO:0000244|PDB:5NG0}. FT STRAND 43 48 {ECO:0000244|PDB:5NG0}. FT STRAND 51 53 {ECO:0000244|PDB:5NG0}. FT HELIX 57 72 {ECO:0000244|PDB:5NG0}. FT STRAND 81 87 {ECO:0000244|PDB:5NG0}. FT STRAND 90 96 {ECO:0000244|PDB:5NG0}. FT HELIX 103 108 {ECO:0000244|PDB:5NG0}. FT TURN 110 112 {ECO:0000244|PDB:5NG0}. FT HELIX 118 136 {ECO:0000244|PDB:5NG0}. FT STRAND 138 140 {ECO:0000244|PDB:5NG0}. FT HELIX 149 151 {ECO:0000244|PDB:5NG0}. FT STRAND 152 154 {ECO:0000244|PDB:5NG0}. FT STRAND 160 162 {ECO:0000244|PDB:5NG0}. FT HELIX 168 176 {ECO:0000244|PDB:5NG3}. FT TURN 189 192 {ECO:0000244|PDB:6ES0}. FT HELIX 195 197 {ECO:0000244|PDB:5NG0}. FT HELIX 202 205 {ECO:0000244|PDB:6ES0}. FT HELIX 210 224 {ECO:0000244|PDB:5NG0}. FT TURN 228 231 {ECO:0000244|PDB:5NG0}. FT HELIX 235 243 {ECO:0000244|PDB:5NG0}. FT TURN 252 254 {ECO:0000244|PDB:5NG0}. FT HELIX 262 272 {ECO:0000244|PDB:5NG0}. FT HELIX 277 279 {ECO:0000244|PDB:5NG0}. FT HELIX 283 295 {ECO:0000244|PDB:5NG0}. FT HELIX 300 312 {ECO:0000244|PDB:6ES0}. FT TURN 313 315 {ECO:0000244|PDB:6ES0}. FT HELIX 436 450 {ECO:0000244|PDB:2N7Z}. FT HELIX 453 465 {ECO:0000244|PDB:2N7Z}. FT HELIX 471 476 {ECO:0000244|PDB:2N7Z}. FT HELIX 483 497 {ECO:0000244|PDB:2N7Z}. FT HELIX 501 511 {ECO:0000244|PDB:2N7Z}. FT STRAND 526 528 {ECO:0000244|PDB:2N7Z}. FT TURN 530 532 {ECO:0000244|PDB:2N83}. SQ SEQUENCE 540 AA; 61195 MW; 575A692239505792 CRC64; MNGEAICSAL PTIPYHKLAD LRYLSRGASG TVSSARHADW RVQVAVKHLH IHTPLLDSER KDVLREAEIL HKARFSYILP ILGICNEPEF LGIVTEYMPN GSLNELLHRK TEYPDVAWPL RFRILHEIAL GVNYLHNMTP PLLHHDLKTQ NILLDNEFHV KIADFGLSKW RMMSLSQSRS SKSAPEGGTI IYMPPENYEP GQKSRASIKH DIYSYAVITW EVLSRKQPFE DVTNPLQIMY SVSQGHRPVI NEESLPYDIP HRARMISLIE SGWAQNPDER PSFLKCLIEL EPVLRTFEEI TFLEAVIQLK KTKLQSVSSA IHLCDKKKME LSLNIPVNHG PQEESCGSSQ LHENSGSPET SRSLPAPQDN DFLSRKAQDC YFMKLHHCPG NHSWDSTISG SQRAAFCDHK TTPCSSAIIN PLSTAGNSER LQPGIAQQWI QSKREDIVNQ MTEACLNQSL DALLSRDLIM KEDYELVSTK PTRTSKVRQL LDTTDIQGEE FAKVIVQKLK DNKQMGLQPY PEILVVSRSP SLNLLQNKSM //