Documents

a) Annotation

In Swiss-Prot, as in many sequence databases, two classes of data can be distinguished: the core data and the annotation.

For each sequence entry the core data consists of:

• The sequence data;
• The citation information (bibliographical references);
• The taxonomic data (description of the biological source of the protein).

The annotation consists of the description of the following items:

• Function(s) of the protein;
• Posttranslational modification(s) such as carbohydrates, phosphorylation, acetylation and GPI-anchor;
• Domains and sites, for example, calcium-binding regions, ATP-binding sites, zinc fingers, homeoboxes, SH2 and SH3 domains and kringle;
• Secondary structure, e.g. alpha helix, beta sheet;
• Quaternary structure, i.g. homodimer, heterotrimer, etc.;
• Similarities to other proteins;
• Disease(s) associated with any number of deficiencies in the protein;
• Sequence conflicts, variants, etc.

We try to include as much annotation information as possible in Swiss-Prot. To obtain this information we use, in addition to the publications that report new sequence data, review articles to periodically update the annotations of families or groups of proteins. We also make use of external experts, who have been recruited to send us their comments and updates concerning specific groups of proteins.

We believe that having systematic recourse both to publications other than those reporting the core data and to subject referees represents a unique and beneficial feature of Swiss-Prot.

In Swiss-Prot, annotation is mainly found in the comment lines (CC), in the feature table (FT) and in the keyword lines (KW). Most comments are classified by 'topics'; this approach permits the easy retrieval of specific categories of data from the database.

b) Minimal redundancy

Many sequence databases contain, for a given protein sequence, separate entries which correspond to different literature reports. In Swiss-Prot we try as much as possible to merge all these data so as to minimize the redundancy of the database. If conflicts exist between various sequencing reports, they are indicated in the feature table of the corresponding entry.

c) Integration with other databases

It is important to provide the users of biomolecular databases with a degree of integration between the three types of sequence-related databases (nucleic acid sequences, protein sequences and protein tertiary structures) as well as with specialized data collections. Swiss-Prot is currently cross-referenced to more than 100 different databases. Cross-references are provided in the form of pointers to information related to Swiss-Prot entries and found in data collections other than Swiss-Prot. This extensive network of cross-references allows Swiss-Prot to play a major role as a focal point of biomolecular database interconnectivity.

d) Documentation

Swiss-Prot is distributed with a large number of index files and specialized documentation files. Some of these files have been available for a long time (this user manual, the release notes, the various indices for authors, citations, keywords, etc.), but many have been created recently and we are continuously adding new files. 'Documentation files' section contains an up-to-date descriptive list of all distributed document files.

a) Automatic annotation

Records waiting in TrEMBL for full manual annotation are enhanced by automatic annotation. Information is transferred from well-characterised entries in Swiss-Prot to unannotated entries in TrEMBL which belong to groups defined by InterPro, a database of protein families, domains and functional sites. This process brings the standard of annotation in TrEMBL closer to that found in Swiss-Prot through the addition of accurate, high-quality information to TrEMBL entries, thus improving the quality of data available to the user.

b) Redundancy removal

Sequences from the same organism which are full-length and which have 100% identity are merged into a single entry to reduce redundancy.

a) An evidence type without source

{ECO:0000305}

{ECO:0000250}

{ECO:0000255}

b) An evidence type with source

{ECO:0000269|PubMed:10433554}

{ECO:0000303|Ref.6}

{ECO:0000305|PubMed:16683188} 

{ECO:0000250|UniProtKB:Q8WUF5}

{ECO:0000312|EMBL:BAG16761.1}

{ECO:0000313|EMBL:BAG16761.1}

{ECO:0000255|HAMAP-Rule:MF_00205}

{ECO:0000256|HAMAP-Rule:MF_00205}

{ECO:0007744|PDB:1K83}

{ECO:0000213|PDB:1K83}

c) Several evidences

{ECO:0000269|PubMed:10433554, ECO:0000303|Ref.6}

3.1.1. Entry name

The first item on the ID line is the entry name of the sequence. This name is a useful means of identifying a sequence, but it is not a stable identifier as is the accession number (see 3.2).

3.1.2. Status

The second item on the ID line indicates the status of the entry (see section 2.2).

3.1.3. Length of the molecule

The third and last item of the ID line is the length of the molecule, which is the total number of amino acids in the sequence. This number includes the positions reported to be present but which have not been determined (coded as 'X'). The length is followed by the letter code 'AA' (Amino Acids).

3.1.4. Examples of identification lines

Two examples of Swiss-Prot ID lines are shown below:

ID   CYC_BOVIN               Reviewed;         104 AA.

ID   GIA2_GIALA              Reviewed;         296 AA.

Example of a TrEMBL ID line:

ID   Q5JU06_HUMAN            Unreviewed;       268 AA.

a) The DE line in Swiss-Prot

The description always starts with the recommended name (RecName) of the protein. Alternative names (AltName) are indicated thereafter.

The DE line contains 3 categories, as well as several subcategories, of protein names:

Category Field	Subcategory Field	Cardinality	Description
RecName:		1 in UniProtKB/Swiss-Prot 0-1 in UniProtKB/TrEMBL	The name recommended by the UniProt consortium.
	Full=	1	The full name.
	Short=	0-n	An abbreviation of the full name or an acronym.
	EC=	0-n	An Enzyme Commission number.
AltName:		0-n	A synonym of the recommended name.
	Full=	0-1	The full name.
	Short=	0-n	An abbreviation of the full name or an acronym.
	EC=	0-n	An Enzyme Commission number.
AltName:	Allergen=	0-1	See allergen.txt.
AltName:	Biotech=	0-1	A name used in a biotechnological context.
AltName:	CD_antigen=	0-n	See cdlist.txt.
AltName:	INN=	0-n	The international nonproprietary name: A generic name for a pharmaceutical substance or active pharmaceutical ingredient that is globally recognized and is a public property.
SubName:		0 in UniProtKB/Swiss-Prot 0-n in UniProtKB/TrEMBL	A name provided by the submitter of the underlying nucleotide sequence.
	Full=	1	The full name.
	EC=	0-n	An Enzyme Commission number.

Each name is shown on a separate line; lines may therefore exceed 80 characters.

Protein naming guidelines are described in the International protein nomenclature guidelines.

DE   RecName: Full=Annexin A5;

DE            Short=Annexin-5;

DE   AltName: Full=Annexin V;

DE   AltName: Full=Lipocortin V;

DE   AltName: Full=Endonexin II;

DE   AltName: Full=Calphobindin I;

DE   AltName: Full=CBP-I;

DE   AltName: Full=Placental anticoagulant protein I;

DE            Short=PAP-I;

DE   AltName: Full=PP4;

DE   AltName: Full=Thromboplastin inhibitor;

DE   AltName: Full=Vascular anticoagulant-alpha;

DE            Short=VAC-alpha;

DE   AltName: Full=Anchorin CII;

DE   RecName: Full=Granulocyte colony-stimulating factor;

DE            Short=G-CSF;

DE   AltName: Full=Pluripoietin;

DE   AltName: Full=Filgrastim;

DE   AltName: Full=Lenograstim;

DE   Flags: Precursor;

A block of DE lines may further contain multiple Includes: and/or Contains: sections and a separate field Flags: to indicate whether the protein sequence is a precursor or a fragment:

Field	Cardinality	Value
Includes:	0-n	A block of protein names as described in the table above.
Contains:	0-n	A block of protein names as described in the table above.
Flags:	0-1	Precursor and/or Fragment or Fragments

If a protein is known to be cleaved into multiple functional components, the description starts with the name of the precursor protein, followed by 'Contains:' section(s). Each individual component is described in a separate 'Contains:' section Alternative names (AltName) are allowed for each individual component. Example:

DE   RecName: Full=Corticotropin-lipotropin;

DE   AltName: Full=Pro-opiomelanocortin;

DE            Short=POMC;

DE   Contains:

DE     RecName: Full=NPP;

DE   Contains:

DE     RecName: Full=Melanotropin gamma;

DE     AltName: Full=Gamma-MSH;

DE   Contains:

DE     RecName: Full=Potential peptide;

DE   Contains:

DE     RecName: Full=Corticotropin;

DE     AltName: Full=Adrenocorticotropic hormone;

DE              Short=ACTH;

DE   Contains:

DE     RecName: Full=Melanotropin alpha;

DE     AltName: Full=Alpha-MSH;

DE   Contains:

DE     RecName: Full=Corticotropin-like intermediary peptide;

DE              Short=CLIP;

DE   Contains:

DE     RecName: Full=Lipotropin beta;

DE     AltName: Full=Beta-LPH;

DE   Contains:

DE     RecName: Full=Lipotropin gamma;

DE     AltName: Full=Gamma-LPH;

DE   Contains:

DE     RecName: Full=Melanotropin beta;

DE     AltName: Full=Beta-MSH;

DE   Contains:

DE     RecName: Full=Beta-endorphin;

DE   Contains:

DE     RecName: Full=Met-enkephalin;

DE   Flags: Precursor;

If a protein is known to include multiple functional domains each of which is described by a different name, the description starts with the name of the overall protein, followed by 'Includes:' section(s). All the domains are listed in a separate 'Includes:' section. Alternative names (AltName) are allowed for each individual domain. Example:

DE   RecName: Full=CAD protein;

DE   Includes:

DE     RecName: Full=Glutamine-dependent carbamoyl-phosphate synthase;

DE              EC=6.3.5.5;

DE   Includes:

DE     RecName: Full=Aspartate carbamoyltransferase;

DE              EC=2.1.3.2;

DE   Includes:

DE     RecName: Full=Dihydroorotase;

DE              EC=3.5.2.3;

In rare cases, the functional domains of an enzyme are cleaved, but the catalytic activity can only be observed, when the individual chains reorganize in a complex. Such proteins are described in the DE line by a combination of both 'Includes:' and 'Contains:', in the order given in the following example:

DE   RecName: Full=Arginine biosynthesis bifunctional protein argJ;

DE   Includes:

DE     RecName: Full=Glutamate N-acetyltransferase;

DE              EC=2.3.1.35;

DE     AltName: Full=Ornithine acetyltransferase;

DE              Short=OATase;

DE     AltName: Full=Ornithine transacetylase;

DE   Includes:

DE     RecName: Full=Amino-acid acetyltransferase;

DE              EC=2.3.1.1;

DE     AltName: Full=N-acetylglutamate synthase;

DE              Short=AGS;

DE   Contains:

DE     RecName: Full=Arginine biosynthesis bifunctional protein argJ alpha chain;

DE   Contains:

DE     RecName: Full=Arginine biosynthesis bifunctional protein argJ beta chain;

When the mature form of a protein is derived by processing of a precursor, we indicate this fact using the Flag 'Precursor'; in such cases the sequence displayed does not correspond to the mature form of the protein.

DE   RecName: Full=Chondroitin proteoglycan 3;

DE   Flags: Precursor;

If the complete sequence is not determined, we indicate it in the 'Flags' section with 'Fragment' or 'Fragments'. Example:

DE   RecName: Full=Dihydrodipicolinate reductase;

DE            Short=DHPR;

DE            EC=1.3.1.26;

DE   Flags: Fragment;

b) The DE line in TrEMBL

The format of the DE line in TrEMBL follows closely the format used in Swiss-Prot. However, as TrEMBL is not manually annotated, the description is derived directly from the underlying nucleotide entry and its accuracy relies on the information provided by the submitter of the nucleotide entry. It is why TrEMBL entries usually have submitted name (SubName) instead of a recommended name (RecName). The description may later be improved by automatic annotation procedures (see section Automatic annotation) but if not, it remains as provided by the submitter until the entry is manually annotated and added to Swiss-Prot.

3.11.1. Introduction

These lines comprise the literature citations. The citations indicate the sources from which the data has been abstracted. The reference lines for a given citation occur in a block, and are always in the order RN, RP, RC, RX, RG, RA, RT and RL. Within each such reference block, the RN line occurs once, the RC, RX and RT lines occur zero or more times, and the RP, RG/RA and RL lines occur one or more times. If several references are given, there will be a reference block for each.

An example of a complete reference is:

RN   [1] {ECO:0000305, ECO:0000312|EMBL:AAK28740.1}

RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND C), FUNCTION, INTERACTION WITH

RP   PKC-3, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND

RP   MUTAGENESIS OF PHE-175 AND PHE-221.

RC   STRAIN=Bristol N2 {ECO:0000269|PubMed:11134024};

RX   PubMed=11134024; DOI=10.1074/jbc.m008990200;

RA   Zhang L., Wu S.-L., Rubin C.S.;

RT   "A novel adapter protein employs a phosphotyrosine binding domain and

RT   exceptionally basic N-terminal domains to capture and localize an atypical

RT   protein kinase C: characterization of Caenorhabditis elegans C kinase

RT   adapter 1, a protein that avidly binds protein kinase C3.";

RL   J. Biol. Chem. 276:10463-10475(2001).

The formats of the individual lines are explained below.

3.11.2. The RN line

The RN (Reference Number) line gives a sequential number to each reference citation in an entry. This number is used to indicate the reference in comments and feature table notes. The format of the RN line is:

RN   [n]

where 'n' denotes the n^th reference for this entry. The reference number is always between square brackets.

3.11.3. The RP line

The RP (Reference Position) lines describe the extent of the work relevant to the entry carried out by the authors. The format of the RP line is:

RP   COMMENT.

It should contain a description of the information that has been propagated in the Swiss-Prot entry.

A typical comment is "NUCLEOTIDE SEQUENCE". This item might be tagged with a qualifier, indicating the origin of the sequence data. Valid names of this qualifiers are:

• GENOMIC DNA: the individual gene has been sequenced
• GENOMIC RNA: the individual gene has been sequenced
• MRNA: the individual cDNA has been sequenced
• LARGE SCALE GENOMIC DNA: the gene has been sequenced as part of a genome project
• LARGE SCALE MRNA: the cDNA has been sequenced as part of a large-scale cDNA project

If 2 qualifiers apply, both are indicated, separated by a '/'.

The 'LARGE SCALE ANALYSIS' is another typical tag added in references that report large screen results to indicate that results have not been extensively studied.

Typical examples of RP lines are shown below:

RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].

RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).

RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA / MRNA].

RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 21-35.

RP   PROTEIN SEQUENCE OF 39-76; 95-118 AND 125-138, AND DISULFIDE BONDS.

RP   SEQUENCE REVISION TO 76-84 AND 129.

RP   STRUCTURE BY NMR.

RP   X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).

RP   CHARACTERIZATION.

RP   MUTAGENESIS OF TYR-65.

RP   REVIEW.

RP   VARIANT ALA-1368.

RP   VARIANTS HDLD1 ARG-597 AND ARG-1477, AND VARIANT HDLD2 LEU-693 DEL.

RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-23; 3-18; 241-257;

RP   319-340 AND 382-391, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY

RP   REGULATION, SUBUNIT, AND DISRUPTION PHENOTYPE.

RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 154-171; 302-308; 312-328;

RP   377-384 AND 419-431, FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF

RP   ARG-331; GLY-332 AND ARG-333.

RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-295; SER-391; SER-479;

RP   SER-491 AND SER-710, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE

RP   ANALYSIS].

3.11.4. The RC line

The RC (Reference Comment) lines are optional lines which are used to store comments relevant to the reference cited. The format of the RC line is:

RC   TOKEN1=Text; TOKEN2=Text; ...

The currently defined tokens and their order in the RC line are:

STRAIN

PLASMID

TRANSPOSON

TISSUE

Reference comment line topics may span lines. Examples of RC lines:

RC   STRAIN=Sprague-Dawley; TISSUE=Liver;

RC   STRAIN=Holstein; TISSUE=Lymph node, and Mammary gland;

RC   STRAIN=301 / Serotype 2a;

RC   STRAIN=cv. SP753012-O; TISSUE=Leaf;

RC   PLASMID=R1 (R7268); TRANSPOSON=Tn3;

RC   STRAIN=AL.012, AZ.026, AZ.180, DC.005, GA.039, GA2181, IL.014, IL2.17,

RC   IN.018, KY.172, KY2.37, LA.013, MI.035, MN.001, MNb027, MS.040, NY.016,

RC   OH.036, TN.173, TN2.38, UT.002, and VA.015;

3.11.5. The RX line

The RX (Reference cross-reference) line is an optional line which is used to indicate the identifier assigned to a specific reference in a bibliographic database. The format of the RX line is:

RX   Bibliographic_db=IDENTIFIER[; Bibliographic_db=IDENTIFIER...];

Where the valid bibliographic database names and their associated identifiers are:

Name	Identifier
MEDLINE	Eight-digit MEDLINE Unique Identifier (UI)
PubMed	PubMed Unique Identifier (PMID)
DOI	Digital Object Identifier (DOI)
AGRICOLA	AGRICOLA Unique Identifier

Example of RX lines:

RX   MEDLINE=83283433; PubMed=6688356;

RX   PubMed=15626370; DOI=10.1016/j.toxicon.2004.10.011;

RX   MEDLINE=22709107; PubMed=12788972; DOI=10.1073/pnas.1130426100;

RX   AGRICOLA=IND20551642; DOI=10.1007/BF00224104;

3.11.6. The RG line

The Reference Group (RG) line lists the consortium name associated with a given citation. The RG line is mainly used in submission reference blocks, but can also be used in paper references, if the working group is cited as an author in the paper. RG line and RA line (Reference Author) can be present in the same reference block; at least one RG or RA line is mandatory per reference block. An example of the use of RG lines is shown below:

RG   The mouse genome sequencing consortium;

3.11.7. The RA line

The RA (Reference Author) lines list the authors of the paper (or other work) cited. The RA line is present in most references, but might be missing in references that cite a reference group (see RG line). At least one RG or RA line is mandatory per reference block.

All of the authors are included, and are listed in the order given in the paper. The names are listed surname first followed by a blank, followed by initial(s) with periods. The authors' names are separated by commas and terminated by a semicolon. Author names are not split between lines. An example of the use of RA lines is shown below:

RA   Galinier A., Bleicher F., Negre D., Perriere G., Duclos B., Cozzone A.J.,

RA   Cortay J.-C.;

As many RA lines as necessary are included in each reference.

An author's initials can be followed by an abbreviation such as 'Jr' (for Junior), 'Sr' (Senior), 'II', 'III' or 'IV' (2nd, 3rd and 4th). Example:

RA   Nasoff M.S., Baker H.V. II, Wolf R.E. Jr.;

3.11.8. The RT line

The RT (Reference Title) lines give the title of the paper (or other work) cited as exactly as possible given the limitations of the computer character set. The format of the RT line is:

RT   "Title.";

Example of a set of RT lines:

RT   "New insulin-like proteins with atypical disulfide bond pattern

RT   characterized in Caenorhabditis elegans by comparative sequence analysis

RT   and homology modeling.";

It should be noted that the format of the title is not always identical to that displayed at the top of the published work:

• Major title words are not capitalized;
• The text of a title ends with either a period '.', a question mark '?' or an exclamation mark '!';
• Double quotation marks ' " ' in the text of the title are replaced by single quotation marks;
• Titles of articles published in a language other than English have been translated into English;
• Greek letters are written in full (alpha, beta, etc.).

3.11.9. The RL line

The RL (Reference Location) lines contain the conventional citation information for the reference. In general, the RL lines alone are sufficient to find the paper in question.

3.12.1. Examples for each comment line topic

We show here, for each of the defined topics, two examples of their usage:

CC   -!- ALLERGEN: Causes an allergic reaction in human. Binds to IgE. Partially

CC       heat-labile allergen that may cause both respiratory and food-allergy

CC       symptoms in patients with the bird-egg syndrome.

CC       {ECO:0000269|PubMed:11488669}.

CC   -!- ALLERGEN: Causes an allergic reaction in human. Minor allergen of

CC       bovine dander.

CC   -!- ALTERNATIVE PRODUCTS:

CC       Event=Alternative splicing; Named isoforms=4;

CC         Comment=Additional isoforms seem to exist. Experimental confirmation

CC         may be lacking for some isoforms.;

CC       Name=1; Synonyms=AIRE-1;

CC         IsoId=O43918-1; Sequence=Displayed;

CC       Name=2; Synonyms=AIRE-2;

CC         IsoId=O43918-2; Sequence=VSP_004089;

CC       Name=3; Synonyms=AIRE-3;

CC         IsoId=O43918-3; Sequence=VSP_004089, VSP_004090;

CC       Name=4;

CC         IsoId=O43918-4; Sequence=VSP_004089, VSP_043529;

CC   -!- ALTERNATIVE PRODUCTS:

CC       Event=Alternative splicing, Alternative initiation; Named isoforms=3;

CC       Name=Alpha;

CC         IsoId=P51636-1; Sequence=Displayed;

CC       Name=Beta;

CC         IsoId=P51636-2; Sequence=VSP_018696;

CC       Name=C;

CC         IsoId=P51636-3; Sequence=VSP_038114, VSP_038115;

CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:

CC       Kinetic parameters:

CC         KM=5 uM for pyridoxal phosphate {ECO:0000269|PubMed:10080917};

CC         KM=12.2 mM for D-alanine {ECO:0000269|PubMed:10080917};

CC         KM=17.9 mM for L-alanine {ECO:0000269|PubMed:10080917};

CC       pH dependence:

CC         Optimum pH is 8-10. {ECO:0000269|PubMed:10080917};

CC       Temperature dependence:

CC         Highly active at low temperatures, even at 0 degree Celsius.

CC         Thermolabile. {ECO:0000269|PubMed:10080917};

CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:

CC       Kinetic parameters:

CC         KM=98 uM for ATP;

CC         KM=688 uM for pyridoxal;

CC         Vmax=1.604 mmol/min/mg enzyme;

CC       pH dependence:

CC         Optimum pH is 6.0. Active from pH 4.5 to 10.5.;

CC   -!- BIOTECHNOLOGY: The effect of PG can be neutralized by introducing an

CC       antisense PG gene by genetic manipulation. The Flavr Savr tomato

CC       produced by Calgene (Monsanto) in such a manner has a longer shelf life

CC       due to delayed ripening.

CC   -!- BIOTECHNOLOGY: Used in the food industry for high temperature

CC       liquefaction of starch-containing mashes and in the detergent industry

CC       to remove starch. Sold under the name Termamyl by Novozymes.

CC   -!- CATALYTIC ACTIVITY:

CC       Reaction=ATP + L-glutamate + NH4(+) = ADP + H(+) + L-glutamine +

CC         phosphate; Xref=Rhea:RHEA:16169, ChEBI:CHEBI:15378,

CC         ChEBI:CHEBI:28938, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616,

CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:58359, ChEBI:CHEBI:456216; EC=6.3.1.2;

CC   -!- CATALYTIC ACTIVITY:

CC       Reaction=(2R)-2,3-dihydroxy-3-methylbutanoate + NADP(+) = (2S)-2-

CC         acetolactate + H(+) + NADPH; Xref=Rhea:RHEA:22068, ChEBI:CHEBI:15378,

CC         ChEBI:CHEBI:49072, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,

CC         ChEBI:CHEBI:58476; EC=1.1.1.86; Evidence={ECO:0000255|HAMAP-

CC         Rule:MF_00435};

CC   -!- CATALYTIC ACTIVITY:

CC       Reaction=(2R,3R)-2,3-dihydroxy-3-methylpentanoate + NADP(+) = (S)-2-

CC         ethyl-2-hydroxy-3-oxobutanoate + H(+) + NADPH; Xref=Rhea:RHEA:13493,

CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:49256, ChEBI:CHEBI:49258,

CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.86;

CC         Evidence={ECO:0000255|HAMAP-Rule:MF_00435};

CC   -!- CAUTION: It is uncertain whether Met-1 or Met-3 is the initiator.

CC       {ECO:0000305}.

CC   -!- COFACTOR:

CC       Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;

CC         Evidence={ECO:0000250|UniProtKB:P15505};

CC   -!- COFACTOR:

CC       Name=FAD; Xref=ChEBI:CHEBI:57692;

CC         Evidence={ECO:0000255|HAMAP-Rule:MF_01202};

CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Amyloid beta entry;

CC       URL="http://en.wikipedia.org/wiki/Amyloid_beta";

CC   -!- DEVELOPMENTAL STAGE: Expressed early during conidial (dormant spores)

CC       differentiation.

CC   -!- DEVELOPMENTAL STAGE: Detected in embryonic skin (12.5 dpc and 14.5 dpc)

CC       during the formation of hair follicles and at 15.5 dpc in the enamel

CC       knot of the developing tooth. Detected in the basal layer of the

CC       epidermis and hair follicles of P2 mice.

CC   -!- DISEASE: Glycogen storage disease 9D (GSD9D) [MIM:300559]: A metabolic

CC       disorder characterized by slowly progressive, predominantly distal

CC       muscle weakness and atrophy. Clinical features include exercise

CC       intolerance with early fatigability, pain, cramps and occasionally

CC       myoglobinuria. {ECO:0000269|PubMed:12825073}. Note=The disease is

CC       caused by mutations affecting the gene represented in this entry.

CC   -!- DISEASE: Adrenoleukodystrophy (ALD) [MIM:300100]: A peroxisomal

CC       metabolic disorder characterized by progressive multifocal

CC       demyelination of the central nervous system and by peripheral adrenal

CC       insufficiency (Addison disease). It results in mental deterioration,

CC       corticospinal tract dysfunction, and cortical blindness. Different

CC       clinical manifestations exist like: cerebral childhood ALD (CALD),

CC       adult cerebral ALD (ACALD), adrenomyeloneuropathy (AMN) and 'Addison

CC       disease only' (ADO) phenotype. {ECO:0000269|PubMed:10369742,

CC       ECO:0000269|PubMed:10480364, ECO:0000269|PubMed:10551832,

CC       ECO:0000269|PubMed:10737980, ECO:0000269|PubMed:10980539,

CC       ECO:0000269|PubMed:11248239, ECO:0000269|PubMed:11438993,

CC       ECO:0000269|PubMed:11810273, ECO:0000269|PubMed:15643618,

CC       ECO:0000269|PubMed:21700483, ECO:0000269|PubMed:21889498,

CC       ECO:0000269|PubMed:23651979, ECO:0000269|PubMed:26686776,

CC       ECO:0000269|PubMed:7581394, ECO:0000269|PubMed:7717396,

CC       ECO:0000269|PubMed:7825602, ECO:0000269|PubMed:7849723,

CC       ECO:0000269|PubMed:7904210, ECO:0000269|PubMed:8040304,

CC       ECO:0000269|PubMed:8566952, ECO:0000269|PubMed:8651290,

CC       ECO:0000269|PubMed:9452087}. Note=The disease is caused by mutations

CC       affecting the gene represented in this entry.

CC   -!- DISEASE: Note=The promoter region of ABCD1 is deleted in the chromosome

CC       Xq28 deletion syndrome which involves ABCD1 and the neighboring gene

CC       BCAP31. {ECO:0000269|PubMed:11992258}.

CC   -!- DISRUPTION PHENOTYPE: Mice display impaired B-cell development which

CC       does not progress pass the progenitor stage.

CC       {ECO:0000269|PubMed:12097390}.

CC   -!- DISRUPTION PHENOTYPE: Death before reaching adulthood, probably due to

CC       lethal epilepsy. Mice display severe defects in the olfactory bulbs,

CC       the hippocampus, and the cerebellum. These defects appear to result

CC       from impaired cytokinesis followed by the induction of apoptosis in

CC       specific neuroblast populations. {ECO:0000269|PubMed:11086988}.

CC   -!- DOMAIN: The N-terminal domain (1-374) is sufficient for the exchange

CC       factor activity.

CC   -!- DOMAIN: The B chain is composed of two domains, each domain consists of

CC       3 homologous subdomains (alpha, beta, gamma).

CC   -!- ACTIVITY REGULATION: The activity of this enzyme could be controlled by

CC       adenylation under conditions of abundant glutamine.

CC       {ECO:0000250|UniProtKB:Q3V5W6}.

CC   -!- ACTIVITY REGULATION: Activated by Gram-negative bacterial

CC       lipopolysaccharides and chymotrypsin.

CC   -!- FUNCTION: Binds to actin and affects the structure of the cytoskeleton.

CC       At high concentrations, profilin prevents the polymerization of actin,

CC       whereas it enhances it at low concentrations. By binding to PIP2, it

CC       inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR)

CC       and HTT aggregation and binding of G-actin is essential for its

CC       inhibition of AR (By similarity). {ECO:0000250}.

CC   -!- FUNCTION: Inhibitor of fungal polygalacturonase. It is an important

CC       factor for plant resistance to phytopathogenic fungi. Substrate

CC       preference is polygalacturonase (PG) from A.niger >> PG of F.oxysporum,

CC       A.solani or B.cinerea. Not active on PG from F.moniliforme.

CC       {ECO:0000269|PubMed:10228150, ECO:0000269|PubMed:9304859}.

CC   -!- INDUCTION: By heat shock, salt stress, oxidative stress, glucose

CC       limitation and oxygen limitation.

CC   -!- INDUCTION: By infection, plant wounding, or elicitor treatment of cell

CC       cultures.

CC   -!- INTERACTION:

CC       P53323; Q03705: CGI121; NbExp=9; IntAct=EBI-3809, EBI-912262;

CC       P53323; P46984: GON7; NbExp=6; IntAct=EBI-3809, EBI-26178;

CC       P53323; Q03835: GRX3; NbExp=3; IntAct=EBI-3809, EBI-22178;

CC       P53323; P32642: GRX4; NbExp=11; IntAct=EBI-3809, EBI-22211;

CC       P53323; P36132: KAE1; NbExp=21; IntAct=EBI-3809, EBI-26411;

CC   -!- INTERACTION:

CC       Q99259; Q6RW13: AGTRAP; NbExp=3; IntAct=EBI-743184, EBI-741181;

CC       Q99259; Q6RW13-2: AGTRAP; NbExp=6; IntAct=EBI-743184, EBI-11522760;

CC       Q99259; Q96DZ9: CMTM5; NbExp=4; IntAct=EBI-743184, EBI-2548702;

CC       Q99259; Q96DZ9-2: CMTM5; NbExp=6; IntAct=EBI-743184, EBI-11522780;

CC       Q99259; P46952: HAAO; NbExp=8; IntAct=EBI-743184, EBI-743215;

CC       Q99259; Q969L2: MAL2; NbExp=6; IntAct=EBI-743184, EBI-944295;

CC       Q99259; P16333: NCK1; NbExp=2; IntAct=EBI-743184, EBI-389883;

CC       Q99259; Q13188: STK3; NbExp=3; IntAct=EBI-743184, EBI-992580;

CC   -!- MASS SPECTROMETRY: Mass=24948; Mass_error=6; Method=MALDI;

CC       Evidence={ECO:0000269|PubMed:11101899};

CC   -!- MASS SPECTROMETRY: Mass=15706; Method=MALDI;

CC       Evidence={ECO:0000269|PubMed:10531593};

CC   -!- MASS SPECTROMETRY: [Isoform B]: Mass=13822; Method=MALDI; Note=The

CC       measured range is 19-140.; Evidence={ECO:0000269|PubMed:10531593};

CC   -!- MISCELLANEOUS: Binds to bacitracin.

CC   -!- MISCELLANEOUS: Called DUO because the encoded protein is closely

CC       related to but shorter than TRIO.

CC   -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX

CC       biosynthesis; 5-aminolevulinate from L-glutamyl-tRNA(Glu): step 2/2.

CC   -!- PATHWAY: Porphyrin-containing compound metabolism; chlorophyll

CC       biosynthesis.

CC   -!- PATHWAY: Nitrogen metabolism; (S)-allantoin degradation.

CC       {ECO:0000255|HAMAP-Rule:MF_00616}.

CC   -!- PHARMACEUTICAL: Available under the names Avonex (Biogen), Betaseron

CC       (Berlex) and Rebif (Serono). Used in the treatment of multiple

CC       sclerosis (MS). Betaseron is a slightly modified form of IFNB1 with two

CC       residue substitutions.

CC   -!- PHARMACEUTICAL: Available under the name Proleukin (Chiron). Used in

CC       patients with renal cell carcinoma or metastatic melanoma.

CC   -!- POLYMORPHISM: The allelic form of the enzyme with Gln-192 (allozyme A)

CC       hydrolyzes paraoxon with a low turnover number and the one with Arg-192

CC       (allozyme B) with a high turnover number. {ECO:0000269|PubMed:7916578,

CC       ECO:0000269|PubMed:8098250}.

CC   -!- POLYMORPHISM: In human populations there are two major allelic forms,

CC       alpha-1 (1-1) with 83 residues and alpha-2 (2-2) with 142 residues.

CC       These alleles determine 3 possible genotypes, homozygous (1-1 or 2-2)

CC       and heterozygous (2-1), and 3 major phenotypes HP*1F/HP*1S and HP*2FS.

CC       The two main alleles of HP*1 are called HP*1F (fast) and HP*1S (slow).

CC       The alleles exhibit different oligomerization properties. In healthy

CC       males, but not in females, the Hp 2-2 phenotype is associated with

CC       higher serum iron, decreased antimicrobial and antioxidant capability,

CC       and less efficient clearance from the circulation, than Hp 1-1 and 2-1.

CC       The sequence displayed in this entry corresponds to allele alpha-2 (2-

CC       2). {ECO:0000269|PubMed:4018023, ECO:0000269|PubMed:6330675,

CC       ECO:0000269|PubMed:6546723}.

CC   -!- PTM: N-glycosylated and probably also O-glycosylated.

CC   -!- PTM: A soluble short form may be released by proteolytic cleavage from

CC       the long membrane-anchored form. {ECO:0000250|UniProtKB:P78423}.

CC   -!- RNA EDITING: Modified_positions=393 {ECO:0000269|PubMed:10611383}, 431

CC       {ECO:0000269|PubMed:10611383}, 472 {ECO:0000269|PubMed:10611383}, 495

CC       {ECO:0000269|PubMed:10611383};

CC   -!- RNA EDITING: Modified_positions=59 {ECO:0000269|PubMed:12527781,

CC       ECO:0000269|PubMed:12711687}, 78 {ECO:0000269|PubMed:12527781,

CC       ECO:0000269|PubMed:12711687}, 94 {ECO:0000269|PubMed:12527781,

CC       ECO:0000269|PubMed:12711687}, 98 {ECO:0000269|PubMed:12527781,

CC       ECO:0000269|PubMed:12711687}, 102 {ECO:0000269|PubMed:12527781,

CC       ECO:0000269|PubMed:12711687}, 121 {ECO:0000269|PubMed:12527781,

CC       ECO:0000269|PubMed:12711687}; Note=The nonsense codon at position 59 is

CC       modified to a sense codon. The stop codon at position 121 is created by

CC       RNA editing.;

CC   -!- SEQUENCE CAUTION:

CC       Sequence=AAA24007.1; Type=Frameshift; Evidence={ECO:0000305};

CC   -!- SIMILARITY: Belongs to the annexin family. {ECO:0000255|PROSITE-

CC       ProRule:PRU01245, ECO:0000305}.

CC   -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor. Golgi

CC       apparatus.

CC   -!- SUBCELLULAR LOCATION: [Megakaryocyte-potentiating factor]: Secreted.

CC   -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted.

CC   -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:11997398,

CC       ECO:0000269|PubMed:1610806, ECO:0000269|PubMed:9837940}.

CC   -!- SUBUNIT: Heterodimer; disulfide-linked heterodimer of a light chain

CC       (LC) and a heavy chain (HC). The LC has the proteolytic/pharmacological

CC       activity, while the N- and C-termini of the HC mediate channel

CC       formation and toxin binding, respectively. Interacts with host

CC       receptors synaptotagmin-1 and -2 (SYT1 and SYT2) (PubMed:15123599,

CC       PubMed:17185412, PubMed:20219474). {ECO:0000269|PubMed:15123599,

CC       ECO:0000269|PubMed:17185412, ECO:0000269|PubMed:20219474}.

CC   -!- TISSUE SPECIFICITY: Shoots, roots, and cotyledon from dehydrating

CC       seedlings.

CC   -!- TISSUE SPECIFICITY: Expressed at high levels in brain and ovary. Lower

CC       levels in small intestine. In brain regions, detected in all regions

CC       tested. Highest levels in the cerebellum and cerebral cortex.

CC   -!- TOXIC DOSE: PD(50) is 0.36 mg/kg by injection in blowfly larvae, in

CC       PubMed:12885226.

CC   -!- TOXIC DOSE: PD(50) is 0.557 mg/kg by injection in blowfly larvae, in

CC       PubMed:15824108.

CC   -!- TOXIC DOSE: [Sarafotoxin-C]: LD(50) is 0.3 mg/kg by intravenous

CC       injection into mice. {ECO:0000269|PubMed:3176048}.

CC   -!- WEB RESOURCE: Name=CD40Lbase; Note=CD40L defect database;

CC       URL="http://bioinf.uta.fi/CD40Lbase/";

3.12.2. Syntax of the topic 'BIOPHYSICOCHEMICAL PROPERTIES'

CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:

CC       Absorption:

CC         Abs(max)=xx nm;

CC         Note=free_text;

CC       Kinetic parameters:

CC         KM=xx unit for substrate [(free_text)];

CC         Vmax=xx unit enzyme [free_text];

CC         Note=free_text;

CC       pH dependence:

CC         free_text;

CC       Redox potential:

CC         free_text;

CC       Temperature dependence:

CC         free_text;

A BIOPHYSICOCHEMICAL PROPERTIES block must contain at least one of the properties Absorption, Kinetic parameters, pH dependence, Redox potential, Temperature dependence and may have any combination of these properties (ordered as indicated above). The meaning of these subtopics is as follows:

Property	Description
Absorption	indicates the wavelength at which photoreactive proteins such as opsins and DNA photolyases show maximal absorption
Kinetic parameters	mentions the Michaelis-Menten constant (KM) and maximal velocity (Vmax) of enzymes
pH dependence	describes the optimum pH for enzyme activity and/or the variation of enzyme activity with pH variation
Redox potential	reports the value of the standard (midpoint) oxido-reduction potential(s) for electron transport proteins
Temperature dependence	indicates the optimum temperature for enzyme activity and/or the variation of enzyme activity with temperature variation; the thermostability/thermolability of the enzyme is also mentioned when it is known

3.12.3. The topic 'INTERACTION'

The CC line topic INTERACTION conveys information relevant to binary protein-protein interaction. It is automatically derived from the IntAct database and is updated at every release. The occurrence is one INTERACTION topic per entry, with each binary interaction being presented in a separate line. Each data line can be longer than 80 characters.

Interactions can be derived by any appropriate experimental method, but must be confirmed by a second experiment, if resulting from a single yeast- two-hybrid experiment. For large-scale experiments, interactions are considered if a high confidence is assigned from the authors.

The format of the CC line topic INTERACTION is:

CC   -!- INTERACTION:

CC       <Interactant>; <Interactant>;( Xeno;)? NbExp=<Experiments>; IntAct=<IntActId>, <IntActId>;

CC       <Interactant>; <Interactant>;( Xeno;)? NbExp=<Experiments>; IntAct=<IntActId>, <IntActId>;

CC       ...

where

• <Interactant> represents a UniProtKB protein.
• the first <Interactant> is represented by: (<Accession>|<IsoId>|<ProductId>)
• the second <Interactant> is represented by: (<Accession>|<IsoId>|<ProductId> [<Accession>])(: <Gene>)?
• <IsoId> is a UniProtKB isoform ID.
• <ProductId> is a UniProtKB product ID, i.e. a feature identifier.
• <Gene> is either the gene name, ordered locus name or ORF name of the gene that encodes the UniProtKB protein.
• <Experiments> is the number of experiments in IntAct that support an interaction.
• <IntActId> is an IntAct protein ID.
• 'Xeno' is an optional flag that indicates that the interacting proteins are derived from different species. This may be due to the experimental set-up or may reflect a pathogen-host interaction.
• IntAct=IntActId, IntActId identifies the interaction in IntAct by using the two IntAct protein identifiers.

Examples:

Binary interactions with different isoforms that are described in P11309.

P11309

CC   -!- INTERACTION:

CC       P11309-1; Q9BZS1-1: FOXP3; NbExp=3; IntAct=EBI-1018629, EBI-9695448;

CC       P11309-2; Q9UNQ0: ABCG2; NbExp=5; IntAct=EBI-1018633, EBI-1569435;

Binary interaction with a product of proteolytic cleavage.

P27958:

CC   -!- INTERACTION:

CC       PRO_0000037566; Q9NPY3: CD93; Xeno; NbExp=2; IntAct=EBI-6377335, EBI-1755002;

Q9NPY3:

CC   -!- INTERACTION:

CC       Q9NPY3; PRO_0000037566 [P27958]; Xeno; NbExp=2; IntAct=EBI-1755002, EBI-6377335;

Examples of interaction lines are given below. The CC INTERACTION topics are not complete; only explained interaction lines are indicated.

CC   -!- INTERACTION:

CC       Q9NQ11; Q2M2I8: AAK1; NbExp=2; IntAct=EBI-6308763, EBI-1383433;

In the typical example the current protein, Q9NQ11, is interacting with Q2M2I8 which is further characterized by its gene name "AAK1". The interaction is supported by two experiments stored in IntAct. Experimental details for this interaction can be found by querying IntAct with "EBI-6308763, EBI-1383433".

CC   -!- INTERACTION:

CC       P27449; Q9UHP7-3: CLEC2D; NbExp=3; IntAct=EBI-721179, EBI-11749983;

The current protein, P27449, interacts with an isoform of Q9UHP7 defined by the IsoID Q9UHP7-3.

CC   -!- INTERACTION:

CC       P62799; P84233; NbExp=2; IntAct=EBI-302085, EBI-350041;

No gene name information for the interacting protein is available.

CC   -!- INTERACTION:

CC       P03612; P03612; NbExp=2; IntAct=EBI-781118, EBI-781118;

The protein self-associates.

CC   -!- INTERACTION:

CC       Q9NVC6; Q9D8C6: Med11; Xeno; NbExp=2; IntAct=EBI-394562, EBI-6260909;

The source organisms of the interacting proteins are different.

CC   -!- INTERACTION:

CC       Q9UNA1; O14613: CDC42EP2; NbExp=3; IntAct=EBI-1390913, EBI-3438291;

CC       Q9UNA1-2; O14613: CDC42EP2; NbExp=3; IntAct=EBI-16430964, EBI-3438291;

Different isoforms of the current protein are shown to interact with the same protein (O14613). This is reflected by different IntActIDs for the current protein.

Example entry with many interaction lines: Q02821.

3.12.4. Syntax of the topic 'SUBCELLULAR LOCATION'

The document subcell.txt, lists the controlled vocabularies used in the comment line (CC) topic SUBCELLULAR LOCATION, their definitions and further information such as synonyms or relevant GO terms in the following format:

    ---------  -------------------------------   ----------------------------------------------

    Line code  Content                           Occurrence in an entry

    ---------  -------------------------------   ----------------------------------------------

    ID         Identifier (location)             Once; starts an entry

    IT         Identifier (topology)             Once; starts a 'topology' entry

    IO         Identifier (orientation)          Once; starts an 'orientation' entry

    AC         Accession (SL-xxxx)               Once

    DE         Definition                        Once or more

    SY         Synonyms                          Optional; Once or more

    SL         Content of subc. loc. lines       Once

    HI         Hierarchy ('is-a')                Optional; Once or more

    HP         Hierarchy ('part-of')             Optional; Once or more

    KW         Associated keyword (accession)    Optional; Once or more

    GO         Gene ontology (GO) mapping        Optional; Once or more

    WW         Interesting links or references   Optional; Once or more

    //         Terminator                        Once; ends an entry

    

   

Example:

    ID   Cyanelle.

    AC   SL-0082

    DE   A cyanelle is a photosynthetic organelle of glaucocystophyte algae.

    DE   Cyanelles are surrounded by a double membrane and, in between, a

    DE   peptidoglycan wall. Thylakoid membrane architecture and the presence

    DE   of carboxysomes are cyanobacteria-like. Historically, the term

    DE   cyanelle is derived from a classification as endosymbiotic

    DE   cyanobacteria, and thus is not fully correct.

    SY   Muroplast; Cyanoplast.

    SL   Plastid, cyanelle.

    HI   Plastid.

    KW   KW-0194

    GO   GO:0009842; cyanelle

    //

   

The format of SUBCELLULAR LOCATION is:

       CC   -!- SUBCELLULAR LOCATION:(( Molecule:)?( Location\.)+)?( Note=Free_text( Flag)?\.)?

   

Where:

• Molecule: Isoform, chain or peptide name
• Location = Subcellular_location( Flag)?(; Topology( Flag)?)?(; Orientation( Flag)?)?
  • Subcellular_location: SL-line of subcell.txt ID-record
  • Topology: SL-line of subcell.txt IT-record
  • Orientation: SL-line of subcell.txt IO-record

Note: Perl-style multipliers indicate whether a pattern (as delimited by parentheses) is optional (?) or may occur 1 or more times (+).

Examples:

When no chain/peptide/isoform is specified, the subcellular location corresponds to that of the mature protein.

CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12867153}.

CC       Endoplasmic reticulum membrane {ECO:0000269|PubMed:12867153};

CC       Peripheral membrane protein {ECO:0000269|PubMed:12867153}. Golgi

CC       apparatus membrane {ECO:0000269|PubMed:12867153}; Peripheral membrane

CC       protein {ECO:0000269|PubMed:12867153}.

   

CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Peripheral membrane

CC       protein {ECO:0000250}. Secreted {ECO:0000250}. Note=The last 22 C-

CC       terminal amino acids may participate in cell membrane attachment.

CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm {ECO:0000305}.

   

CC   -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane

CC       {ECO:0000269|PubMed:17919502, ECO:0000269|PubMed:19033537,

CC       ECO:0000269|PubMed:22240481, ECO:0000269|PubMed:24706876}; Multi-pass

CC       membrane protein {ECO:0000255}. Late endosome

CC       {ECO:0000269|PubMed:11231950, ECO:0000269|PubMed:15681833}.

CC       Note=Predominantly found in the trans-Golgi network (TGN). Localized in

CC       the trans-Golgi network under low copper conditions, redistributes to

CC       cytoplasmic vesicles when cells are exposed to elevated copper levels,

CC       and then recycles back to the trans-Golgi network when copper is

CC       removed (PubMed:10942420). {ECO:0000269|PubMed:10942420,

CC       ECO:0000269|PubMed:22240481, ECO:0000269|PubMed:24706876,

CC       ECO:0000269|PubMed:9307043}.

CC   -!- SUBCELLULAR LOCATION: [Isoform 1]: Golgi apparatus membrane

CC       {ECO:0000269|PubMed:9307043}; Multi-pass membrane protein

CC       {ECO:0000269|PubMed:9307043}.

CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm

CC       {ECO:0000269|PubMed:9307043}.

CC   -!- SUBCELLULAR LOCATION: [WND/140 kDa]: Mitochondrion

CC       {ECO:0000269|PubMed:9600907}.

   

3.12.5. Syntax of the topic 'ALTERNATIVE PRODUCTS'

The format of the CC line topic ALTERNATIVE PRODUCTS is:

 CC   -!- ALTERNATIVE PRODUCTS:

 CC       Event=Event(, Event)*; Named isoforms=Number_of_isoforms;

(CC         Comment=Free_text;)?

(CC       Name=Isoform_name;( Synonyms=Synonym(, Synonym)*;)?

 CC         IsoId=Isoform_identifier(, Isoform_identifer)*;

 CC         Sequence=(Displayed|External|Not described|Feature_identifier(, Feature_identifier)*);

(CC         Note=Free_text;)?)+

Note: Variable values are represented in italics. Perl-style multipliers indicate whether a pattern (as delimited by parentheses) is optional (?), may occur 0 or more times (*), or 1 or more times (+). Alternative values are separated by a pipe symbol (|).

Topic	Description
Event	Biological process that results in the production of the alternative forms. It lists one or a combination of the following values (Alternative promoter usage, Alternative splicing, Alternative initiation, Ribosomal frameshifting). Format: Event=controlled vocabulary; Example: Event=Alternative splicing;
Named isoforms	Number of isoforms listed in the topics 'Name' currently only for 'Event=Alternative splicing'. Format: Named isoforms=number; Example: Named isoforms=6;
Comment	Any comments concerning one or more isoforms; optional; Format: Comment=free text; Example: Comment=Experimental confirmation may be lacking for some isoforms;
Name	A common name for an isoform used in the literature or assigned by Swiss-Prot; currenty only available for spliced isoforms. Format: Name=common name; Example: Name=Alpha;
Synonyms	Synonyms for an isoform as used in the literature; optional; currently only available for spliced isoforms. Format: Synonyms=Synonym_1[, Synonym_n]; Example: Synonyms=B, KL5;
IsoId	Unique identifier for an isoform, consisting of the Swiss-Prot accession number, followed by a dash and a number. Format: IsoId=acc#-isoform_number[, acc#-isoform_number]; Example: IsoId=P05067-1;
Sequence	Information on the isoform sequence; the term 'Displayed' indicates, that the sequence is shown in the entry; a lists of feature identifiers (VSP_#) indicates that the isoform is annotated in the feature table; the FTIds enable programs to create the sequence of a splice variant; if the accession number of the IsoId does not correspond to the accession number of the current entry, this topic contains the term 'External'; 'Not described' points out that the sequence of the isoform is unknown. Format: Sequence=VSP_#[, VSP_#]|Displayed|External|Not described; Example: Sequence=Displayed; Example: Sequence=VSP_000013, VSP_000014; Example: Sequence=External; Example: Sequence=Not described;
Note	Lists isoform-specific information; optional. It may specify the event(s), if there are several. Format: Note=Free text; Example: Note=No experimental confirmation available;

Example of the CC lines and the corresponding FT lines for an entry with alternative splicing:

CC   -!- ALTERNATIVE PRODUCTS:

CC       Event=Alternative promoter usage, Alternative splicing; Named isoforms=11;

CC       Name=1; Synonyms=Non-muscle isozyme;

CC         IsoId=Q15746-1; Sequence=Displayed;

CC       Name=2;

CC         IsoId=Q15746-2; Sequence=VSP_004791;

CC       Name=3A;

CC         IsoId=Q15746-3; Sequence=VSP_004794;

CC       Name=3B;

CC         IsoId=Q15746-4; Sequence=VSP_004791, VSP_004794;

CC       Name=4;

CC         IsoId=Q15746-5; Sequence=VSP_004793;

CC       Name=Del-1790;

CC         IsoId=Q15746-6; Sequence=VSP_004795;

CC       Name=5; Synonyms=Smooth-muscle isozyme;

CC         IsoId=Q15746-7; Sequence=VSP_018845;

CC       Name=6; Synonyms=Telokin;

CC         IsoId=Q15746-8; Sequence=VSP_018846;

CC       Name=7;

CC         IsoId=Q15746-9; Sequence=VSP_053791;

CC       Name=8;

CC         IsoId=Q15746-10; Sequence=VSP_018846, VSP_004795;

CC       Name=9;

CC         IsoId=Q15746-11; Sequence=VSP_018845, VSP_004795;

...

FT   VAR_SEQ         1..1760

FT                   /note="Missing (in isoform 6 and isoform 8)"

FT                   /evidence="ECO:0000303|PubMed:10536370,

FT                   ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334"

FT                   /id="VSP_018846"

FT   VAR_SEQ         1..1200

FT                   /note="Missing (in isoform 7)"

FT                   /evidence="ECO:0000303|PubMed:14702039"

FT                   /id="VSP_053791"

FT   VAR_SEQ         1..922

FT                   /note="Missing (in isoform 5 and isoform 9)"

FT                   /evidence="ECO:0000303|PubMed:8575746, ECO:0000303|Ref.8"

FT                   /id="VSP_018845"

FT   VAR_SEQ         437..506

FT                   /note="VSGIPKPEVAWFLEGTPVRRQEGSIEVYEDAGSHYLCLLKARTRDSGTYSCT

FT                   ASNAQGQLSCSWTLQVER -> G (in isoform 2 and isoform 3B)"

FT                   /evidence="ECO:0000303|PubMed:10198165,

FT                   ECO:0000303|PubMed:15507455"

FT                   /id="VSP_004791"

FT   VAR_SEQ         1473..1545

FT                   /note="Missing (in isoform 4)"

FT                   /evidence="ECO:0000303|PubMed:10198165"

FT                   /id="VSP_004793"

FT   VAR_SEQ         1655..1705

FT                   /note="Missing (in isoform 3A and isoform 3B)"

FT                   /evidence="ECO:0000303|PubMed:10198165"

FT                   /id="VSP_004794"

FT   VAR_SEQ         1790

FT                   /note="Missing (in isoform Del-1790, isoform 8 and isoform

FT                   9)"

FT                   /evidence="ECO:0000303|PubMed:10536370,

FT                   ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,

FT                   ECO:0000303|PubMed:8575746"

FT                   /id="VSP_004795"

CC   -!- ALTERNATIVE PRODUCTS:

CC       Event=Alternative splicing, Alternative initiation; Named isoforms=3;

CC         Comment=Isoform 1 and isoform tumor suppressor ARF arise due to the

CC         use of two alternative first exons joined to a common exon 2 at the

CC         same acceptor site but in different reading frames, resulting in two

CC         completely different isoforms.;

CC       Name=1; Synonyms=CDKN2A, p16INK4a;

CC         IsoId=O77617-1; Sequence=Displayed;

CC       Name=3;

CC         IsoId=O77617-2; Sequence=VSP_018701;

CC       Name=tumor suppressor ARF; Synonyms=p19ARF;

CC         IsoId=O77618-1; Sequence=External;

..

FT   VAR_SEQ         1..34

FT                   /note="Missing (in isoform 3)"

FT                   /evidence="ECO:0000305"

FT                   /id="VSP_018701"

3.12.6. Syntax of the topic 'MASS SPECTROMETRY'

CC   -!- MASS SPECTROMETRY: ([ProductName]: )?Mass=mass(; Mass_error=error)?; Method=method; (; Note=free_text)?; Evidence=references;

Where:

• 'ProductName' is the name of an isoform or product of proteolytic cleavage;
• 'Mass=XXX' is the determined molecular weight (MW);
• 'Mass_error=XX' (optional) is the accuracy or error range of the MW measurement;
• 'Method=XX' is the ionization method;
• 'Note={Free text}'. Comment in free text format;
• 'Evidence=PubMed:/Ref.n' indicates the relevant reference'.

3.12.7. DISRUPTION PHENOTYPE

Note that we only describe effects caused the complete absence of a gene and thus a protein in vivo (null mutants caused by random or target deletions, insertions of a transposable element etc.) To avoid description of phenotypes due to partial or dominant negative mutants, missense mutations are not described in this comment, but in FT MUTAGEN instead. Defects caused by transient inactivation by methods such as RNA interference (RNAi) or blockage by antibodies are not described in this comment due to the difficulty to interpret results, except for C. elegans RNAi studies, which are widely used and done in vivo.

3.12.8. Syntax of the topic 'SEQUENCE CAUTION'

The format of the SEQUENCE CAUTION topic is:

CC   -!- SEQUENCE CAUTION:

         Sequence=Sequence; Type=Type;[ Note=Note;]

Where:

• Sequence is the sequence which differs from the UniProtKB sequence. It is described by one of:
  • an EMBL protein identifier (with version number)
  • an EMBL accession number.
  • a literature reference (e.g. Ref.3).
• Type describes the cause for the sequence difference(s) and is one of:
  • Frameshift
  • Erroneous initiation
  • Erroneous termination
  • Erroneous gene model prediction
  • Erroneous translation
  • Miscellaneous discrepancy
• Note is an optional free text explanation.

These lines will not be wrapped and their length may therefore exceed 80 characters.

3.12.9. Syntax of the topic 'WEB RESOURCE'

CC   -!- WEB RESOURCE: ([ProductName]: )?Name=ResourceName[; Note=FreeText][; URL=WWWAddress].

Where:

• 'ProductName' is the name of an isoform or product of proteolytic cleavage;
• 'Name' is the name of the database;
• 'Note' (optional) is a free text note;
• 'URL' is the WWW address (URL) of the database;

The length of these lines may exceed 80 characters because long URL addresses are not wrapped into multiple lines.

3.13.1. Definition

The DR (Database cross-Reference) lines are used as pointers to information in external data resources that is related to UniProtKB entries. The full list of all databases to which UniProtKB is cross-referenced can be found in the document dbxref.txt. It also contains references describing these resources and provides links to their web sites.

For example, if the X-ray crystallographic atomic coordinates of a sequence are stored in the Protein Data Bank (PDB) there will be one DR line pointing to each of the corresponding entries in PDB. For a sequence translated from a nucleotide sequence there will be DR line(s) pointing to the relevant entri(es) in the EMBL/GenBank/DDBJ database which correspond to the DNA or RNA sequence(s) from which it was translated.

The format of the DR line is:

DR   RESOURCE_ABBREVIATION; RESOURCE_IDENTIFIER; OPTIONAL_INFORMATION_1[; OPTIONAL_INFORMATION_2][; OPTIONAL_INFORMATION_3].

The cross-references to the EMBL/GenBank/DDBJ nucleotide sequence database and PROSITE are described in sections 3.13.2 and 3.13.3.

Examples of complete DR lines are shown here:

DR   EMBL; U29082; AAA68403.1; -; Genomic_DNA.

DR   ABCD; O75084; 10 sequenced antibodies.

DR   AGR; WB:WBGene00000467; -.

DR   Allergome; 3541; Asc s 1.0101.

DR   AlphaFoldDB; A8H2R3; -.

DR   Antibodypedia; 740; 5394 antibodies.

DR   ArachnoServer; AS000173; kappa-hexatoxin-Hv1b.

DR   Araport; AT4G08920; -.

DR   Bgee; ENSRNOG00000001873; Expressed in 9 organ(s), highest expression level in skeletal muscle tissue.

DR   BindingDB; P06709; -.

DR   BioCyc; EcoCyc:USHA-MONOMER; -.

DR   BioGRID; 69392; 1.

DR   BioGRID-ORCS; 55343; 19 Hits in 787 CRISPR Screens.

DR   BioMuta; TF; -.

DR   BMRB; A1D240; -.

DR   BRENDA; 3.5.99.5; 3804.

DR   CarbonylDB; Q14789; -.

DR   CAZy; GH109; Glycoside Hydrolase Family 109.

DR   CCDS; CCDS18166.1; -. [O89019-1]

DR   CDD; cd01948; EAL; 1.

DR   ChEMBL; CHEMBL4259; -.

DR   ChiTaRS; ATP6AP1; drosophila.

DR   CGD; CAL0001939; orf19.773.

DR   CollecTF; EXPREG_00000150; -.

DR   COMPLUYEAST-2DPAGE; P41797; -.

DR   ConoServer; 2838; ArIA precursor.

DR   CORUM; P59998; -.

DR   CPTAC; CPTAC-311; -.

DR   CPTC; P31751; 6 antibodies.

DR   CTD; 282646; -.

DR   dictyBase; DDB0191351; myoB.

DR   DIP; DIP:37N; -.

DR   DisGeNET; 348; -.

DR   DisProt; DP00239; -.

DR   DMDM; 44887889; -.

DR   DNASU; 1400; -.

DR   DOSAC-COBS-2DPAGE; P02774; -.

DR   DrugBank; APRD00096; Tegaserod.

DR   DrugCentral; P35372; -.

DR   EchoBASE; EB4119; -.

DR   eggNOG; ENOG410IEUN; Eukaryota.

DR   ELM; P12931; -.

DR   Ensembl; ENST00000383775.4; ENSP00000373285.4; ENSG00000154813.10. [Q96FX2-2]

DR   EnsemblBacteria; EBSTAT00000032812; EBSTAP00000031682; EBSTAG00000032810.

DR   EnsemblFungi; YDR365W-B; YDR365W-B; YDR365W-B.

DR   EnsemblMetazoa; FBtr0071603; FBpp0071529; FBgn0020306.

DR   EnsemblPlants; AT1G66340.1; AT1G66340.1; AT1G66340.

DR   EnsemblProtists; DDB0305146; DDB0305146; DDB_G0286833.

DR   EPD; P00451; -.

DR   ESTHER; bacbr-grsb; Thioesterase.

DR   euHCVdb; AF271632; -.

DR   VEuPathDB; GiardiaDB:GL50803_13101; -.

DR   EvolutionaryTrace; P06611; -.

DR   ExpressionAtlas; Q10Q48; baseline.

DR   FlyBase; FBgn0000055; Adh.

DR   Gene3D; 3.40.710.10; DD-peptidase/beta-lactamase superfamily; 1.

DR   GeneCards; LIPE; -.

DR   GeneID; 36674; -.

DR   GeneReviews; MAGEL2; -.

DR   GeneTree; EMGT00050000006238; -.

DR   Genevisible; P31946; HS.

DR   GeneWiki; Dock7; -.

DR   GenomeRNAi; 37724; -.

DR   GlyConnect; 1545; 8 N-Linked glycans (1 site).

DR   GlyCosmos; P24387; 1 site, 6 glycans.

DR   GlyGen; P13591; 6 sites, 2 N-linked glycans (1 site).

DR   GO; GO:0003677; F:DNA binding; IPI:SGD.

DR   Gramene; OS03T0727600-01; OS03T0727600-01; OS03G0727600.

DR   GuidetoPHARMACOLOGY; 2242; -.

DR   HGNC; HGNC:12849; YWHAB.

DR   HAMAP; MF_00120; GatA; 1.

DR   HOGENOM; CLU_142929_0_0_1; -.

DR   HPA; CAB004311; -.

DR   IDEAL; IID00450; -.

DR   IMGT_GENE-DB; IGHM; -.

DR   InParanoid; O04196; -.

DR   IntAct; P14653; 1.

DR   InterPro; IPR001650; Helicase_C.

DR   iPTMnet; Q15796; -.

DR   jPOST; P49429; -.

DR   KEGG; bsu:BG10490; -.

DR   LegioList; lpp2301; -.

DR   Leproma; ML0485; -.

DR   MaizeGDB; 25342; -.

DR   MalaCards; LIPE; -.

DR   MANE-Select; ENST00000314888.10; ENSP00000316029.9; NM_006289.4; NP_006280.3. [Q9Y490-1]

DR   MassIVE; Q8IY92; -.

DR   MaxQB; O94656; -.

DR   MEROPS; M41.009; -.

DR   MetOSite; P10987; -.

DR   MGI; MGI:87920; Adfp.

DR   MIM; 140050; gene.

DR   MINT; MINT-640764; -.

DR   MoonDB; P02730; Curated.

DR   MoonProt; P02730; -.

DR   CLAE; MAN26A_PIRSP; -.

DR   neXtProt; NX_Q69383; -.

DR   NIAGADS; ENSG00000203710; -.

DR   OGP; P31946; -.

DR   OMA; GLCHYFS; -.

DR   OpenTargets; ENSG00000157764; -.

DR   Orphanet; 64; Alstrom syndrome.

DR   OrthoDB; EOG94QWM6; -.

DR   PANTHER; PTHR12103; HAD-IG-Ncltidse; 1.

DR   PathwayCommons; P01042; -.

DR   PATRIC; fig|511145.12.peg.1604; -.

DR   PaxDb; P85829; -.

DR   PCDDB; Q70Q12; -.

DR   PDB; 1NB3; X-ray; 2.80 A; A/B/C/D=116-335, P/R/S/T=98-105.

DR   PDBsum; 1HF1; -.

DR   PeptideAtlas; P32494; -.

DR   PeroxiBase; 79; AtPrx03.

DR   Pfam; PF00017; SH2; 1.

DR   PharmGKB; PA134908332; -.

DR   Pharos; Q7Z3E2; Tdark.

DR   PHI-base; PHI:5282; -.   

DR   PhosphoSitePlus; P01266; -.

DR   PhylomeDB; A4WFL4; -.

DR   PIR; A00682; KIPGA.

DR   PlantReactome; R-OSA-5608118; Auxin signalling.

DR   PIRSF; PIRSF006414; Ftr_formyl_trnsf; 1.

DR   PomBase; SPAC1565.08; cdc48.

DR   PRIDE; P10144; -.

DR   PRINTS; PR00237; GPCRRHODOPSN.

DR   PRO; PR:O42634; -.

DR   ProMEX; P49200; -.

DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 2.

DR   ProteomicsDB; 62174; -.

DR   PseudoCAP; PA0892; -.

DR   Reactome; REACT_1675.1; mRNA Processing.

DR   REBASE; 993; EcoRI.

DR   RefSeq; NP_611010.4; NM_137166.4.

DR   REPRODUCTION-2DPAGE; IPI00022774; -.

DR   RGD; 70968; Ddah1.

DR   RNAct; Q9Y2I1; protein.

DR   SABIO-RK; P10172; -.

DR   SASBDB; Q15326; -.

DR   SFLD; SFLDS00014; RuBisCO; 1.

DR   SGD; S000000170; AAR2.

DR   SignaLink; P41935; -.

DR   SIGNOR; P00533; -.

DR   SMART; SM00369; LRR_TYP; 2.

DR   SMR; P38479; -.

DR   STRING; P23946; -.

DR   SUPFAM; SSF48371; ARM-type_fold; 1.

DR   SWISS-2DPAGE; P10599; -.

DR   SwissLipids; SLP:000000316; -.   

DR   SwissPalm; Q13530; -.

DR   TAIR; locus:2064097; AT2G38610.

DR   TCDB; 1.A.1.11.11; voltage-gated ion channel (VIC) superfamily.

DR   TIGRFAMs; TIGR00630; uvra; 1.

DR   TopDownProteomics; P10599-1; -. [P10599-1]

DR   TreeFam; TF324882; -.

DR   TubercuList; Rv0001; -.

DR   UCD-2DPAGE; P02648; -.

DR   UCSC; uc001olc.4; human. [A5YM72-3]

DR   UniLectin; P84801; -.

DR   UniPathway; UPA00842; UER00808.

DR   VGNC; VGNC:29101; FOXP1.

DR   World-2DPAGE; 0001:P77845; -.

DR   WormBase; F26C11.2; CE01560; WBGene00006744; unc-4.

DR   WBParaSite; Bm6838; Bm6838; WBGene00227099.

DR   Xenbase; XB-FEAT-481105; hdac3.

DR   ZFIN; ZDB-GENE-980526-290; hoxb1b.

3.13.2. Cross-references to the nucleotide sequence database

The specific format for cross-references to the EMBL/GenBank/DDBJ nucleotide sequence database is:

DR   EMBL; ACCESSION_NUMBER; PROTEIN_ID; STATUS_IDENTIFIER; MOLECULE_TYPE.

where 'PROTEIN_ID' stands for the 'Protein Sequence Identifier'. It is a string which is stored, in nucleotide sequence entries, in a qualifier called '/protein_id' which is tagged to every CDS in the nucleotide database. Example from EMBL:

FT   CDS 302..2674

FT   /protein_id="CAA03857.1"

FT   /db_xref="SWISS-PROT:P26345"

FT   /gene="recA"

FT   /product="RecA protein"

The Protein Sequence Identifier (Protein_ID) consists of a stable ID portion (8 characters: 3 letters followed by 5 numbers) plus a period and a version number. The version number only changes when the protein sequence coded by the CDS changes, while the stable part remains unchanged. The Protein_ID effectively replaces what was previously known as the 'PID'.

The 'STATUS_IDENTIFIER' provides information about the relationship between the sequence in the entry and the CDS in the corresponding EMBL entry:

a) In most cases the translation of the EMBL nucleotide sequence CDS results in the same sequence as shown in the corresponding entry or the differences are mentioned in the feature (FT) lines as CONFLICT, VARIANT or VAR_SEQ and in the RP lines. The status identifier is then a dash ('-').

Example:

DR   EMBL; AJ297977; CAC17465.1; -; Genomic_DNA.

DR   EMBL; X56491; CAA39846.1; ALT_FRAME; mRNA.

b) In some cases the translation of the EMBL nucleotide sequence CDS results in a sequence different from the sequence shown in the corresponding entry. When the differences are either not mentioned in the feature (FT) lines as CONFLICT, VARIANT or VAR_SEQ (see below) and in the RP lines, or do simply not meet the criteria for such situations, the differences are indicated as follows:

1. If the difference is due to a different start of the sequence (i.e. Swiss-Prot believes that the start of the sequence is upstream or downstream of the site annotated as the start of the sequence in the EMBL database), the status identifier shows the comment 'ALT_INIT'. Example:

DR   EMBL; L29151; AAA99430.1; ALT_INIT; mRNA.

2. If the difference is due to a different termination of the sequence (i.e. Swiss-Prot believes that the termination of the sequence is upstream or downstream of the site annotated as the end of the sequence in the EMBL database), the status identifier shows the comment 'ALT_TERM'. Example:

DR   EMBL; L20562; AAA26884.1; ALT_TERM; Genomic_DNA.

3. If the difference is due to frameshifts in the EMBL sequence, the status identifier shows the comment 'ALT_FRAME'. Example:

DR   EMBL; X56420; CAA39814.1; ALT_FRAME; mRNA.

4. If the difference is not due to any of the cases mentioned above (e.g. wrong intron-exon boundaries given in the EMBL entry) or to a mixture of the cases mentioned above, the status identifier shows the comment 'ALT_SEQ'. Example:

DR   EMBL; M28482; AAA26378.1; ALT_SEQ; Genomic_DNA.

c) In some cases the nucleotide sequence of a complete CDS is divided into exons present in different EMBL entries. We point to the exon-containing EMBL entries by citing the Protein_ID as optional information field 1 and adding the comment 'JOINED' as the status identifier. These EMBL entries do not contain a CDS feature but contain exons joined to a CDS feature which is labeled with the given Protein_ID.

Example:

DR   EMBL; M63397; AAA51662.1; -; Genomic_DNA.

DR   EMBL; M63395; AAA51662.1; JOINED; Genomic_DNA.

DR   EMBL; M63396; AAA51662.1; JOINED; Genomic_DNA.

In the above example the Swiss-Prot sequence is derived from the CDS labeled with the Protein_ID AAA51662. This CDS feature can be found in the EMBL entry M63397. Exons belonging to this CDS are not only found in EMBL entry M63397, but also in the EMBL entries M63395 and M63396.

d) In some cases there is no CDS feature key annotating a protein translation in an EMBL entry and thus no Protein_ID for the CDS. Therefore it is not possible for us to point to a Protein_ID in the optional information field 1. In these cases we point to the relevant EMBL entries by including a dash ('-') in the position of the missing Protein_ID and 'NOT_ANNOTATED_CDS' into the status identifier.

Example:

DR   EMBL; AJ243418; -; NOT_ANNOTATED_CDS; mRNA.

The 'MOLECULE_TYPE' provides information about the biological source of the molecule. The molecule type is controlled vocabulary, which corresponds to that of The International Nucleotide Sequence Database Collaboration (INSD) comprised of DDBJ (Japan), the EMBL-Bank(UK) and GenBank (USA). Relevant to the UniProt Knowledgebase are the following values:

• Genomic_DNA: any genomic DNA; includes nuclear, organelle, plasmid ...
• Genomic_RNA: genomic RNA
• Transcribed_RNA: any transcribed RNA that is not mRNA; includes unmature RNA (pre-RNA)
• mRNA: mRNA; includes cDNA
• Viral_cRNA: positive cRNA molecule from a single stranded genomic RNA
• Unassigned_DNA: unknown in vivo DNA
• Unassigned_RNA: unknown in vivo RNA
• Other_DNA: synthetic DNA
• Other_RNA: synthetic RNA
• -: unknown

3.13.3. Cross-references to the PROSITE database

The specific format for cross-references to the PROSITE protein domain and family database is:

DR   PROSITE; ACCESSION_NUMBER; ENTRY_NAME; NUMBER_OF_MATCHES.

Where 'ACCESSION_NUMBER' stands for the accession number of the PROSITE pattern or profile entry; 'ENTRY_NAME' is the name of the entry and 'NUMBER_OF_MATCHES' is the number of matches of the pattern or profile in that particular protein sequence.

Examples of PROSITE cross-references:

DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 2.

DR   PROSITE; PS00028; ZINC_FINGER_C2H2_1; 4.

3.16.1. Feature identifiers

Some features are associated with unique and stable feature identifiers (FTId), which allows to construct links directly from position-specific annotation in the feature table to specialized protein-related databases.

Feature identifiers currently exist for the feature keys CARBOHYD, CHAIN, PEPTIDE, PROPEP, VARIANT and VAR_SEQ. Each of these feature types is associated with a 3-letter code feature identifier prefix, which is separated by an underscore from a 6 to 10-digit number. The format of the corresponding FTIds is shown in the following table:

Feature type	Format of the FTId	Availability
CARBOHYD	CAR_number	Currently only for residues attached to an oligosaccharide structure annotated in the GlyConnect database
CHAIN, PEPTIDE	PRO_number	Any mature polypeptide
PROPEP	PRO_number	Any processed propeptide
VARIANT	VAR_number	Currently only for protein sequence variants of Hominidae (great apes and humans)
VAR_SEQ	VSP_number	Any sequence with a VAR_SEQ feature

Examples of features with FTIds are given below:

FT   CHAIN           25..614

FT                   /note="Uromodulin"

FT                   /id="PRO_0000041671"

FT   CHAIN           25..587

FT                   /note="Uromodulin, secreted form"

FT                   /id="PRO_0000407909"

FT   PROPEP          615..640

FT                   /note="Removed in mature form"

FT                   /evidence="ECO:0000255"

FT                   /id="PRO_0000041672"

FT   CARBOHYD        275

FT                   /note="N-linked (GlcNAc...) asparagine"

FT                   /id="CAR_000178"

FT   VAR_SEQ         29

FT                   /note="A -> ARTKYNCPARWSWRTPQRGGDTEQGPDEDFTSQG (in isoform

FT                   5)"

FT                   /evidence="ECO:0000303|PubMed:14702039"

FT                   /id="VSP_054828"

FT   VAR_SEQ         67..199

FT                   /note="Missing (in isoform 2)"

FT                   /evidence="ECO:0000303|PubMed:14702039"

FT                   /id="VSP_017565"

FT   PEPTIDE         20..57

FT                   /note="Histatin-1"

FT                   /id="PRO_0000021416"

FT   PEPTIDE         31..57

FT                   /note="His1-(31-57)-peptide"

FT                   /id="PRO_0000021417"

3.16.2. List of feature types

SIGNAL - Extent of a signal sequence (prepeptide).

FT   SIGNAL          1..26

FT                   /evidence="ECO:0000269|PubMed:11017100"

FT   SIGNAL          1..23

FT                   /evidence="ECO:0000255"

PROPEP - Extent of a propeptide.

Examples:

FT   PROPEP          20..53

FT                   /note="Activation peptide"

FT                   /evidence="ECO:0000269|PubMed:2334440,

FT                   ECO:0000269|PubMed:8346912"

FT                   /id="PRO_0000025974"

FT   PROPEP          550..574

FT                   /note="Removed in mature form"

FT                   /id="PRO_0000000016"

TRANSIT - Extent of a transit peptide (mitochondrion, chloroplast, thylakoid, cyanelle, peroxisome etc.).

Examples:

FT   TRANSIT         1..42

FT                   /note="Chloroplast"

FT                   /evidence="ECO:0000269|PubMed:1912506"

FT   TRANSIT         1..65

FT                   /note="Cyanelle"

FT                   /evidence="ECO:0000269|PubMed:8490125"

FT   TRANSIT         1..25

FT                   /note="Mitochondrion"

FT                   /evidence="ECO:0000250"

FT   TRANSIT         1..36

FT                   /note="Glyoxysome"

FT                   /evidence="ECO:0000269|PubMed:15670147, ECO:0000269|Ref.2"

FT   TRANSIT         1..?

FT                   /note="Chloroplast"

FT                   /evidence="ECO:0000255"

FT   TRANSIT         ?..77

FT                   /note="Thylakoid"

FT                   /evidence="ECO:0000269|PubMed:11719511,

FT                   ECO:0000269|PubMed:11826309"

CHAIN - Extent of a polypeptide chain in the mature protein.

• In Swiss-Prot, it is present:
  1. For proteins that are not processed (those for which the mature protein sequence corresponds to the translated cDNA sequence) the CHAIN covers the whole protein sequence:

     FT   CHAIN           2..334
     
     FT                   /note="COP9 signalosome complex subunit 5"
     
     FT                   /id="PRO_0000194835"
     
     	

  2. For processed proteins, it describes the mature part of the protein once preprotein parts such as propeptides and signal sequences have been removed:

     FT   CHAIN           21..119
     
     FT                   /note="Beta-2-microglobulin"
     
     FT                   /id="PRO_0000018751"
     
     	

     FT   CHAIN           41..180
     
     FT                   /note="Factor X light chain"
     
     FT                   /id="PRO_0000027781"
     
     	

• For TrEMBL, it is present only in those entries where the submitters to the nucleotide sequence databases have provided this information for processed proteins.

PEPTIDE - Extent of a released active peptide.

Examples:

FT   PEPTIDE         1..9

FT                   /note="Arg-vasopressin"

FT                   /id="PRO_0000020507"

FT   PEPTIDE         235..239

FT                   /note="Met-enkephalin"

FT                   /id="PRO_0000024953"

TOPO_DOM - Topological domain.

Examples:

FT   TOPO_DOM        337..371

FT                   /note="Cytoplasmic"

FT   TOPO_DOM        17..471

FT                   /note="Mitochondrial matrix"

FT                   /evidence="ECO:0000255"

TRANSMEM - Extent of a transmembrane region.

Examples:

FT   TRANSMEM        241..264

FT                   /note="Helical"

FT   TRANSMEM        184..204

FT                   /note="Helical"

FT                   /evidence="ECO:0000255"

FT   TRANSMEM        171..191

FT                   /note="Helical; Name=3"

FT                   /evidence="ECO:0000255"

FT   TRANSMEM        1660..1677

FT                   /note="Helical; Name=S5 of repeat IV"

FT                   /evidence="ECO:0000250|UniProtKB:D0E0C2"

FT   TRANSMEM        490..516

FT                   /note="Helical; Anchor for type IV membrane protein"

FT                   /evidence="ECO:0000250"

FT   TRANSMEM        26..35

FT                   /note="Beta stranded"

INTRAMEM - Extent of a region located in a membrane without crossing it.

Examples:

FT   INTRAMEM        306..320

FT   INTRAMEM        1145..1165

FT                   /evidence="ECO:0000255"

FT   INTRAMEM        258..266

FT                   /note="Helical"

FT                   /evidence="ECO:0000250"

FT   INTRAMEM        260..282

FT                   /note="Pore-forming; Name=P region"

FT                   /evidence="ECO:0000255"

FT   INTRAMEM        500..514

FT                   /note="Helical"

FT                   /evidence="ECO:0000250"

FT   INTRAMEM        515..517

FT                   /note="Note=Loop between two helices"

FT                   /evidence="ECO:0000250"

FT   INTRAMEM        518..529

FT                   /note="Helical"

FT                   /evidence="ECO:0000250"

FT   INTRAMEM        530..534

FT                   /note="Note=Loop between two helices"

FT                   /evidence="ECO:0000250"

FT   INTRAMEM        412..423

FT                   /note="Helical; Name=Pore helix"

FT                   /evidence="ECO:0000250|UniProtKB:P63142"

DOMAIN - Extent of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.

The domain type is given in the description field. If there exist several copies of a domain, the domains are numbered.

Examples:

FT   DOMAIN          27..128

FT                   /note="Cadherin 1"

FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"

FT   DOMAIN          745..939

FT                   /note="Ras-GAP"

FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00167"

FT   DOMAIN          746..805

FT                   /note="SH3"

FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"

REPEAT - Extent of an internal sequence repetition.

Examples:

FT   REPEAT          225..307

FT                   /note="1"

FT   REPEAT          341..423

FT                   /note="2"

FT   REPEAT          455..537

FT                   /note="3; approximate"

ZN_FING - Extent of a zinc finger region.

The zinc finger 'category' is indicated in the description field. Examples of ZN_FING key feature lines:

FT   ZN_FING         803..827

FT                   /note="GATA-type"

FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00094"

FT   ZN_FING         560..580

FT                   /note="NR C4-type"

FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"

DNA_BIND - Extent of a DNA-binding region.

The nature of the DNA-binding region is given in the description field. Examples of DNA_BIND key feature lines:

FT   DNA_BIND        335..415

FT                   /note="ETS"

FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00237"

FT   DNA_BIND        69..128

FT                   /note="Homeobox"

FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"

FT   DNA_BIND        44..67

FT                   /note="H-T-H motif"

FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00625"

FT   DNA_BIND        133..207

FT                   /note="TEA"

FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00505"

REGION - Extent of a region of interest in the sequence.

Examples:

FT   REGION          620..631

FT                   /note="Zymogen activation region"

FT   REGION          46..70

FT                   /note="Possesses antibiotic activity"

FT                   /evidence="ECO:0000269|PubMed:8506327"

COILED - Extent of a coiled-coil region.

Example:

FT   COILED          258..553

FT                   /evidence="ECO:0000255"

MOTIF - Short (up to 20 amino acids) sequence motif of biological interest.

Examples:

FT   MOTIF           94..101

FT                   /note="Nuclear localization signal"

FT                   /evidence="ECO:0000269|PubMed:10894149"

FT   MOTIF           648..650

FT                   /note="Microbody targeting signal"

FT                   /evidence="ECO:0000255"

COMPBIAS - Extent of a compositionally biased region.

Examples:

FT   COMPBIAS        683..704

FT                   /note="Polar residues"

FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"

FT   COMPBIAS        711..735

FT                   /note="Basic and acidic residues"

FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"

FT   COMPBIAS        467..495

FT                   /note="Polar residues"

FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"

FT   COMPBIAS        498..532

FT                   /note="Pro residues"

FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"

FT   COMPBIAS        917..942

FT                   /note="Polar residues"

FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"

ACT_SITE - Amino acid(s) involved in the activity of an enzyme.

Examples of ACT_SITE key feature lines:

FT   ACT_SITE        238

FT                   /note="Proton acceptor"

FT   ACT_SITE        1083

FT                   /note="Charge relay system; for serine protease NS3

FT                   activity"

FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01166"

BINDING - Binding site for any chemical group (co-enzyme, prosthetic group, etc.), site of interaction between protein residues and a chemical entity.

The chemical nature of the group is given in the description field.

'Binding site' annotations are structured in a way that allows to standardize the description of a ligand, and optionally the bound part of the ligand, with the ChEBI ontology. The vast majority of ligands that are curated in UniProKB are small molecules that can be represented by a ChEBI entity. A minority of curated ligands are macromolecules. These are not within the scope of ChEBI, but ChEBI contains a limited set of high-level terms (such as DNA or RNA) that we use to curate such ligands. For macromolecules and chelating structures, we sometimes (if known and of interest) also describe the bound part of the ligand with a separate ChEBI entity.

The following placeholders are used for annotation values:

Ligand: Placeholders for values that describe the molecule (small or macro), ion or chelating structure that is bound by the protein:

• LigandName: The UniProt ChEBI name of the ligand, or the word "substrate". Mandatory.
• LigandId: The ChEBI identifier of the ligand. Mandatory, except when the LigandName is "substrate".
• LigandLabel: A label used to distinguish individual instances of a ligand when a protein binds multiple ligands of the same chemical nature. Optional.
• LigandNote: A free text note that provides further details about the ligand. Optional.

Ligand part: Placeholders for values that describe the specific part of the ligand that is bound by the protein (e.g. the iron atom in a heme, a specific type of amino-acid residue in a protein, the 3'-CCA end of a tRNA molecule):

• LigandPartName: The UniProt ChEBI name of the ligand part. Optional.
• LigandPartId: The ChEBI identifier of the ligand part. Optional.
• LigandPartLabel: A label used to distinguish individual instances of a ligand part when a protein binds multiple parts of the same chemical nature that are part of the same ligand. Optional.
• LigandPartNote: A free text note that provides further details about the ligand part. Optional.

Additional information: Placeholders for values that provide additional information:

• Note: Free text note about the binding residue(s). Optional.
• Evidences: List of evidences that support the annotation. Optional.

'Binding site' annotations are used primarily to describe individual amino acid residues that bind a ligand, but may also describe a range of amino acids when the exact ligand binding residues are unknown or where adjacent ligand binding residues had been grouped in the past. Eight qualifiers are used for the BINDING feature type to describe a ligand (/ligand, /ligand_id, /ligand_label, /ligand_note) and a ligand part (/ligand_part, /ligand_part_id, /ligand_part_label, /ligand_part_note).

FT   BINDING         x[..y]

FT                   /ligand="LigandName"

FT                   /ligand_id="ChEBI:LigandId"

FT                   /ligand_label="LigandLabel"

FT                   /ligand_note="LigandNote"

FT                   /ligand_part="LigandPartName"

FT                   /ligand_part_id="ChEBI:LigandPartId"

FT                   /ligand_part_label="LigandPartLabel"

FT                   /ligand_part_note="LigandPartNote"

FT                   /note="Note"

FT                   /evidence="Evidences"

Examples:

FT   BINDING         15

FT                   /ligand="heme c"

FT                   /ligand_id="ChEBI:CHEBI:61717"

FT                   /note="covalent"

FT   BINDING         130..138

FT                   /ligand="chloride"

FT                   /ligand_id="ChEBI:CHEBI:17996"

FT                   /evidence="ECO:0000269|PubMed:12235163,

FT                   ECO:0007744|PDB:1LK9"

SITE - Any interesting single amino-acid site on the sequence, that is not defined by another feature key. It can also apply to an amino acid bond which is represented by the positions of the two flanking amino acids.

Example:

FT   SITE            391..392

FT                   /note="Cleavage; by thrombin"

NON_STD - Non-standard amino acid

This key describes the occurrence of non-standard amino acids selenocysteine and pyrrolysine. Note that we also display them in the sequence data section and use the IUPAC/IUBMB recommended one-letter codes 'U' for selenocysteine and 'O' for pyrrolysine

FT   NON_STD         52

FT                   /note="Selenocysteine"

FT   NON_STD         356

FT                   /note="Pyrrolysine"

FT                   /evidence="ECO:0000250"

MOD_RES - Posttranslational modification of a residue.

The chemical nature of the modified residue is given in the note.

The nature of the posttranslationally formed amino acid is annotated by using a controlled vocabulary; the currently defined list of controlled vocabulary, as well as other information such as the target amino acid, the related keyword, the species where the modification is annotated and the location of the mature protein are available in ptmlist.txt document. Links to example proteins and to the RESID database are also provided to help gain a better insight into every modification.

Modification	extent
ACETYLATION	N-terminal of some residues and side chain of lysine
AMIDATION	Generally at the C-terminal of a mature active peptide after oxidative cleavage of last glycine
BLOCKED	Unidentified N- or C-terminal blocking group
FORMYLATION	Generally of the N-terminal methionine
GAMMA-CARBOXYGLUTAMIC ACID	Of glutamate
HYDROXYLATION	Generally of asparagine, aspartate, proline or lysine
METHYLATION	Generally of N-terminal phenylalanine, side chain of lysine, arginine, histidine, asparagine or glutamate, and C-terminal cysteine
PHOSPHORYLATION	Of serine, threonine, tyrosine, aspartate, histidine or cysteine, and, more rarely, of arginine
PYRROLIDONE CARBOXYLIC ACID	N-terminal glutamine which has formed an internal cyclic lactam. This is also called 'pyro-Glu'. Very rarely, pyro-Glu can be produced by modification of a N-terminal glutamate
SULFATION	Of tyrosine, serine or threonine

Examples:

FT   MOD_RES         2

FT                   /note="N-acetylalanine"

FT                   /evidence="ECO:0000269|PubMed:3754823"

FT   MOD_RES         58

FT                   /note="Methionine amide"

FT                   /evidence="ECO:0000250"

FT   MOD_RES         52

FT                   /note="N6-methyllysine"

FT                   /evidence="ECO:0000255"

FT   MOD_RES         245

FT                   /note="N6-succinyllysine"

FT                   /evidence="ECO:0000250|UniProtKB:P48962"

FT   MOD_RES         206

FT                   /note="Phosphoserine; by CK1"

FT                   /evidence="ECO:0000269|PubMed:8999878"

FT   MOD_RES         217

FT                   /note="Sulfotyrosine"

FT                   /evidence="ECO:0000255"

Example of a feature where the identity of the amino acid is unknown (an X is shown at this position in the sequence):

FT   MOD_RES         1

FT                   /note="Blocked amino end (Xaa)"

LIPID - Covalent binding of a lipid moiety

The chemical nature of the bound lipid moiety is given in the /note.

The attached groups that are currently defined are listed below.

Attached group	Description
myristate	Myristate group attached through an amide bond to the N-terminal glycine residue of the mature form of a protein [1,2] or to an internal lysine residue. The myristate can also be attached through a thioester bond to an internal cysteine
palmitate	Palmitate group attached through an amide bond to the N-terminal cysteine of the mature form of a protein, or to an internal lysine. The palmitate can also be attached through a thioester bond to an internal cysteine or through an ester bond to a serine or threonine residue [1,2]
farnesyl	Farnesyl group attached through a thioether bond to a cysteine residue [3,4]
geranyl-geranyl	Geranyl-geranyl group attached through a thioether bond to a cysteine residue [3,4]
GPI-anchor	Glycosyl-phosphatidylinositol (GPI) group linked to the alpha-carboxyl group of the C-terminal residue of the mature form of a protein [5,6]
diacylglyceride	Glyceryl group bearing two ester-linked fatty acids attached through a thioether bond to the N-terminal cysteine of the mature form of a prokaryotic lipoprotein [7]
archaeol	Archaeol (2,3-di-O-phytanyl-sn-glycerol) lipid group attached through an thioether bond to the N-terminal cysteine of the mature form of a archaeal lipoprotein [8]
n-octanoate	n-octanoate group linked through an ester bond to a serine residue
cholesterol	Cholesterol group attached through an ester bond to the C-terminal glycine of the mature form of a protein

References:

1. Grand R.J.A.
   Biochem. J. 258:626-638(1989).
2. McIlhinney R.A.J.
   Trends Biochem. Sci. 15:387-391(1990).
3. Glomset J.A., Gelb M.H., Farnsworth C.C.
   Trends Biochem. Sci. 15:139-142(1990).
4. Sinensky M., Lutz R.J.
   BioEssays 14:25-31(1992).
5. Low M.G.
   FASEB J. 3:1600-1608(1989).
6. Low M.G.
   Biochim. Biophys. Acta 988:427-454(1989).
7. Hayashi S., Wu H.C.
   J. Bioenerg. Biomembr. 22:451-471(1990).
8. Nishihara M., Utagawa M., Akutsu H., Koga Y.
   J. Biol. Chem. 267:12432-12435(1992).

Examples:

FT   LIPID           2

FT                   /note="N-myristoyl glycine; by host"

FT                   /evidence="ECO:0000250"

FT   LIPID           6

FT                   /note="S-palmitoyl cysteine"

FT                   /evidence="ECO:0000305|PubMed:10364453"

FT   LIPID           231

FT                   /note="GPI-anchor amidated serine"

FT                   /evidence="ECO:0000250|UniProtKB:P04273"

FT   LIPID           21

FT                   /note="S-diacylglycerol cysteine"

FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00843"

The nature of the posttranslationally formed amino acid is annotated by using a controlled vocabulary; the currently defined list of controlled vocabulary, as well as other information such as the target amino acid, the related keyword, the species where the modification is annotated and the location of the mature protein are available in ptmlist.txt document. Links to example proteins and to the RESID database are also provided to help gain a better insight into every modification.

CARBOHYD - Glycosylation site.

This key describes the occurrence of the attachment of a glycan (mono- or polysaccharide) to a residue of the protein:

• The type of linkage (C-, N-, O- or S-linked) to the protein is indicated.
• If the nature of the reducing terminal sugar is known, its abbreviation is shown between parenthesis. If three dots '...' follow the abbreviation, this indicates an extension of the carbohydrate chain. Conversely, the absence of dots means that a monosaccharide is linked.

Examples:

FT   CARBOHYD        53

FT                   /note="N-linked (GlcNAc...) asparagine"

FT                   /evidence="ECO:0000269|PubMed:19159218"

FT   CARBOHYD        1486

FT                   /note="O-linked (GlcNAc) threonine"

FT                   /evidence="ECO:0000269|PubMed:1629228"

FT                   /id="CAR_000155"

FT   CARBOHYD        195

FT                   /note="O-linked (Glc...) tyrosine"

FT                   /evidence="ECO:0007744|PDB:3U2U, ECO:0007744|PDB:3U2V,

FT                   ECO:0000269|PubMed:22160680, ECO:0000269|PubMed:30356213"

FT   CARBOHYD        41

FT                   /note="S-linked (Glc) cysteine"

FT                   /evidence="ECO:0000269|PubMed:21196935,

FT                   ECO:0000269|PubMed:21251913"

FT   CARBOHYD        29

FT                   /note="C-linked (Man) tryptophan"

FT                   /evidence="ECO:0000269|PubMed:10551839"

FT   CARBOHYD        32

FT                   /note="C-linked (Man) tryptophan; partial"

FT                   /evidence="ECO:0000269|PubMed:10551839"

FT   CARBOHYD        38

FT                   /note="O-linked (Fuc...) threonine"

FT                   /evidence="ECO:0000305|PubMed:22267737"

FT   CARBOHYD        152

FT                   /note="O-linked (Ara...) hydroxyproline"

FT                   /evidence="ECO:0000305|PubMed:666730"

The nature of the glycosylated amino acid is annotated by using a controlled vocabulary, which also includes information such as the target amino acid, the related keyword, the species where the modification is annotated and the location of the mature protein and is available in ptmlist.txt document. Links to example proteins and to the RESID database are also provided to help gain a better insight into every modification.

DISULFID - Disulfide bond.

The 'FROM' and 'TO' endpoints designate the two residues which are linked by an intra-chain disulfide bond. If only one position is given, the disulfide bond is an interchain one and the description field indicates the nature of the cross-link.

Examples:

FT   DISULFID        5..103

FT                   /evidence="ECO:0000250"

FT   DISULFID        23..84

FT                   /evidence="ECO:0000305"

FT   DISULFID        30

FT                   /note="Interchain (between small and large chains, with C-

FT                   101 in large chain)"

CROSSLNK - Posttranslationally formed amino acid bonds.

The 'FROM' and 'TO' endpoints designate the two residues, which are linked by an intrachain bond, and the /note field indicates the nature of the cross-link. If there is only one position, the amino acid bond is an interchain one. The name of the linked peptide is indicated in the description field.

Examples:

FT   CROSSLNK        1010..1013

FT                   /note="Isoglutamyl cysteine thioester (Cys-Gln)"

FT   CROSSLNK        60..77

FT                   /note="Beta-methyllanthionine (Cys-Thr)"

FT   CROSSLNK        63..73

FT                   /note="Lanthionine (Ser-Cys)"

FT   CROSSLNK        64..70

FT                   /note="Beta-methyllanthionine (Cys-Thr)"

FT   CROSSLNK        65..78

FT                   /note="Lysinoalanine (Ser-Lys)"

The nature of the posttranslationally formed amino acid bond is annotated by using a controlled vocabulary; the currently defined list of controlled vocabulary, as well as other information such as the target amino acid, the related keyword, the species where the modification is annotated and the location of the mature protein are available in ptmlist.txt document. Links to example proteins and to the RESID database are also provided to help gain a better insight into every modification.

VAR_SEQ - Description of sequence variants produced by alternative splicing, alternative promoter usage, alternative initiation and ribosomal frameshifting.

Examples:

FT   VAR_SEQ         653..672

FT                   /note="VATSNPGKCLSFTNSTFTFT -> ALVSHHCPVEAVRAVHPTRL (in

FT                   isoform 2)"

FT                   /evidence="ECO:0000303|PubMed:12034717,

FT                   ECO:0000303|PubMed:12435728"

FT                   /id="VSP_003786"

FT   VAR_SEQ         673..913

FT                   /note="Missing (in isoform 2)"

FT                   /evidence="ECO:0000303|PubMed:12034717,

FT                   ECO:0000303|PubMed:12435728"

FT                   /id="VSP_003787"

VARIANT - Authors report that sequence variants exist.

Examples:

FT   VARIANT         214

FT                   /note="V -> I (in dbSNP:rs111642750)"

FT                   /evidence="ECO:0000269|Ref.9"

FT                   /id="VAR_009122"

FT   VARIANT         237

FT                   /note="I -> L (in strain: B293, Z3524, Z3910, Z3915 and

FT                   Z3918)"

FT   VARIANT         21..22

FT                   /note="Missing (in 35% of the chains)"

FT                   /id="VAR_006353"

FT   VARIANT         265..296

FT                   /note="Missing (in allele D4.2)"

FT                   /evidence="ECO:0000269|PubMed:1840645"

FT                   /id="VAR_003465"

FT   VARIANT         156

FT                   /note="I -> V (in RNA edited version)"

FT                   /id="VAR_010166"

Explicit links are present in protein sequence entries of Hominidae to the Single Nucleotide Polymorphism database (dbSNP) (Nucleic Acids Res. 29:308-311(2001); PMID: 11125122). The dbSNP identifiers in human FT VARIANT lines are prefixed by "rs". NCBI/dbSNP has rs and ss numbers, but we only refer to SNPs with rs numbers. The format of such links is:

FT   VARIANT        location

FT                  /note=description (in dbSNP:rsaccession_number).

FT                  /id=VAR_number.

Example of a feature with a link to dbSNP:

FT   VARIANT         246

FT                   /note="S -> A (in dbSNP:rs2228541)"

FT                   /evidence="ECO:0000269|PubMed:15489334"

FT                   /id="VAR_024350"

MUTAGEN - Site which has been experimentally altered by mutagenesis.

Examples:

FT   MUTAGEN         119

FT                   /note="C->R,E,A: Loss of cADPr hydrolase and ADP-ribosyl

FT                   cyclase activity."

FT                   /evidence="ECO:0000269|PubMed:7961800"

FT   MUTAGEN         169..177

FT                   /note="Missing: Abolishes ATP-binding."

UNSURE - Uncertainties in the sequence

Used to describe region(s) of a sequence for which the authors are unsure about the sequence assignment.

FT   UNSURE          12

FT                   /note="V or Y"

CONFLICT - Different sources report differing sequences.

Examples:

FT   CONFLICT        728

FT                   /note="Missing (in Ref. 4; AAH40259 and 5; AAL15446)"

FT                   /evidence="ECO:0000305"

FT   CONFLICT        802

FT                   /note="Q -> K (in Ref. 2; no nucleotide entry and 3;

FT                   AAA35793/AAA35794)"

FT                   /evidence="ECO:0000305"

FT   CONFLICT        6..10

FT                   /note="GSDSE -> RIRLR (in Ref. 2; AAD51365)"

FT                   /evidence="ECO:0000305"

FT   CONFLICT        405

FT                   /note="V -> A (in Ref. 10; AAF71067)"

FT                   /evidence="ECO:0000305"

NON_CONS - Non-consecutive residues.

Indicates that two residues in a sequence are not consecutive and that there are a number of unsequenced residues between them. Example of a NON_CONS key feature line:

FT   NON_CONS        52..53

FT                   /evidence="ECO:0000305"

NON_TER - The residue at an extremity of the sequence is not the terminal residue.

If applied to position 1, this means that the first position is not the N-terminus of the complete molecule. If applied to the last position, it means that this position is not the C-terminus of the complete molecule. There is no description field for this key.

Examples:

FT   NON_TER         1

FT   NON_TER         29

Secondary structure (HELIX, STRAND, TURN) - The feature table of sequence entries of proteins whose tertiary structure is known experimentally contains the secondary structure information corresponding to that protein. The secondary structure assignment is made according to DSSP (see Kabsch W., Sander C.; Biopolymers, 22:2577-2637(1983)) and the information is extracted from the coordinate data sets of the Protein Data Bank (PDB).

In the feature table only three types of secondary structure are specified: helices (key HELIX), beta-strands (key STRAND) and turns (key TURN). Residues not specified in one of these classes are in a 'loop' or 'random-coil' structure. Because the DSSP assignment has more than the three common secondary structure classes, we have converted the different DSSP assignments to HELIX, STRAND and TURN as shown in the table below.

DSSP code	DSSP definition	Swiss-Prot assignment
H	Alpha-helix	HELIX
G	3(10) helix	HELIX
I	Pi-helix	HELIX
E	Hydrogen-bonded beta-strand (extended strand)	STRAND
B	Residue in an isolated beta-bridge	STRAND
T	H-bonded turn (3-turn, 4-turn or 5-turn)	TURN
S	Bend (five-residue bend centered at residue i)	Not specified

One should be aware of the following facts:

1. Segment length. For helices (alpha and 3-10), the residue just before and just after the helix as given by DSSP participates in the helical hydrogen-bonding pattern with a single H-bond. For practical purposes, one can extend the HELIX range by one residue on each side, e.g. HELIX 25-35 instead of HELIX 26-34. Also, the ends of secondary structure segments are less well defined for lower-resolution structures. A fluctuation of one residue is common.
2. Missing segments. In low-resolution structures, badly formed helices or strands may be omitted in the DSSP definition.
3. Special helices and strands. Helices of length three are 3-10 helices, those of length four and longer are either alpha-helices or 3-10 helices (pi helices are extremely rare). A strand of one residue corresponds to a residue in an isolated beta-bridge. Such bridges can be structurally important.
4. Missing secondary structure. No secondary structure is currently given in the feature table in the following cases:
   • No sequence data in the PDB entry;
   • Structure for which only C-alpha coordinates are in PDB;
   • NMR structure with more than one coordinate data set.

Examples:

FT   HELIX           3..12

FT                   /evidence="ECO:0007744|PDB:1HB6"

FT   HELIX           13..15

FT                   /evidence="ECO:0007744|PDB:1HB6"

FT   STRAND          16..18

FT                   /evidence="ECO:0007744|PDB:1ACA"

FT   HELIX           22..36

FT                   /evidence="ECO:0007744|PDB:1HB6"

FT   HELIX           50..61

FT                   /evidence="ECO:0007744|PDB:1HB6"

FT   TURN            62..64

FT                   /evidence="ECO:0007744|PDB:1HB6"

FT   HELIX           67..85

FT                   /evidence="ECO:0007744|PDB:1HB6"

B.2.1 The ID line (IDentification)

Differences with the EMBL database ID line format are:

• The entry name can be up to 10 characters long (instead of 9 in EMBL) and can begin with a numerical character;
• EMBL entry ID lines have an additional three-letter taxonomic division 'token' inserted between the status and the molecule type;
• The molecule type is not listed;
• The length of the molecule is followed by 'AA' (Amino Acid) instead of 'BP' (Base Pairs).

B.2.2 The AC line (ACcession number)

The format of this line type is identical to that defined by the EMBL database. Swiss-Prot and TrEMBL accession numbers do not overlap those used in the EMBL/GenBank/DDBJ nucleotide sequence database. However, it should be noted that there are differences in the format of the accession numbers themselves. In Swiss-Prot and TrEMBL accession numbers consist of 6 alphanumerical characters in the following format:

1	2	3	4	5	6
[A-N,R-Z]	[0-9]	[A-Z]	[A-Z, 0-9]	[A-Z, 0-9]	[0-9]
[O,P,Q]	[0-9]	[A-Z, 0-9]	[A-Z, 0-9]	[A-Z, 0-9]	[0-9]

Examples: P01234; Q1AA12.

In EMBL, two different types of accession numbers co-exist:

1. Accession numbers with 6 alphanumerical characters, where the first character is any letter with the exception of O,P or Q and the five other characters are numbers (example: M23765);
2. Accession numbers with 8 alphanumerical characters, where the first two characters are letters and the following six characters are numbers (example: AB001084).

B.2.3 The DT line (DaTe)

Differences with the EMBL database DT line format are:

• In EMBL there are two DT lines per entry whereas there are three in Swiss-Prot;
• In EMBL the format of the DT line that indicates when an entry was created is identical to that defined in Swiss-Prot; but the two DT lines that convey information relevant to the updating of an entry are replaced by a single line in EMBL. This is shown in the example below.

DT lines in a Swiss-Prot entry:

DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.

DT   01-OCT-1989, sequence version 1.

DT   07-FEB-2006, entry version 76.

DT lines in an EMBL database entry:

DT   10-MAR-1990 (Rel. 22, Created)

DT   12-APR-1990 (Rel. 23, Last updated, Version 3)

B.2.4 The DE line (DEscription)

• In the UniProt Knowledgebase the species of origin is not included in the description;
• In EMBL the last DE line is not terminated by a period.

B.2.5 The OS line (Organism Species)

• In EMBL the last OS line is not terminated by a period.

B.2.6 The OG line (OrGanelle)

• EMBL makes a distinction between 'Mitochondrion', and 'Kinetoplast', while Swiss-Prot does not use the latter designation;
• EMBL makes a distinction between 'Chloroplast' and 'Plastid', while Swiss-Prot does not use the latter designation;
• In EMBL the OG line is not terminated by a period.

B.2.7 The RP and RC lines

• In EMBL, unlike Swiss-Prot, the RC line precedes the RP line;
• In EMBL the RC line is in free format and is generally not used.

B.2.8 The RT line (Reference Title)

In EMBL the reference title is not terminated by a period, a question mark or an exclamation mark.

B.2.9 The FT line (Feature Table)

The format of this line is totally different from that currently defined for the EMBL database. The format used in Swiss-Prot is similar to that which was used in older versions of the EMBL database, prior to the introduction of the common EMBL/GenBank/DDBJ feature table.

B.2.10 The CC line (Comment)

The comment lines, which are free text and can appear anywhere in an EMBL entry, are grouped together in the Swiss-Prot database. They are always listed below the last reference line, and follow a precise syntax (see section 3.12).

B.2.11 The SQ line (SeQuence header)

Although the rough format and purpose of this line type is conserved, its exact content differs from that of the EMBL database. The numerical length of the sequence is listed, followed by 'AA' (Amino Acid) instead of 'BP' (Base Pairs). Rather then indicating the sequence composition which, for protein sequences, would not fit in a single line, the molecular weight and the 64-bit CRC (Cyclic Redundancy Check) value of the sequence are indicated.