Table of contents

Format change in the cross-references to HOGENOM and HOVERGEN
Introduction of the new event types 'Protein splicing' and 'Miscellaneous' in the comment line (CC) topic ALTERNATIVE PRODUCTS
Change of the comment line (CC) topic INTERACTION

Not before: 15-Dec-2009

We are going to modify the cross-references to the HOGENOM and HOVERGEN databases: The primary identifier, which is currently a UniProtKB accession number, will be replaced by a HOGENOM and HOVERGEN identifier, resp. The secondary identifier will remain a dash '-'.

Example:

Current format:

DR   HOGENOM; Q9D8H7; -.

DR   HOVERGEN; Q9D8H7; -.

New format:

DR   HOGENOM; HBG025762; -.

DR   HOVERGEN; HBG074595; -.

Not before: 15-Dec-2009

The comment line topic ALTERNATIVE PRODUCTS, together with the feature key VAR_SEQ, describes alternative protein sequences (isoforms) that are the result of alternative splicing, alternative initiation, alternative promoter usage and ribosomal frameshifting events.

We are going to broaden this topic with the new event type Protein splicing to describe protein sequences that arise by intein processing events. Note that other protein maturation events, such as the hedgehog protein processing or other types of cleavages, will not be described by this event.

We will also introduce the general event type Miscellaneous to describe uncommon molecular mechanisms, such as ribosome shunt, ribosome skipping (PMID:12522142) or ribosome termination-reinitiation (PMID:18056426) events.

Example with intein:

Current format:

FT   INIT_MET      1      1       Removed.
FT   CHAIN         2    283       Vacuolar ATP synthase catalytic subunit
FT                                A, 1st part.
FT                                /FTId=PRO_0000002458.
FT   CHAIN       284    737       Endonuclease PI-SceI.
FT                                /FTId=PRO_0000002459.
FT   CHAIN       738   1071       Vacuolar ATP synthase catalytic subunit
FT                                A, 2nd part.
FT                                /FTId=PRO_0000002460.

New format:

CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Protein splicing; Named isoforms=3;
CC         Comment=This protein undergoes a protein self splicing that
CC         involves a post-translational excision of the intervening region
CC         (intein) followed by peptide ligation;
CC       Name=Intein-containing vacuolar ATP synthase catalytic subunit A;
CC         IsoId=P17255-1; Sequence=Displayed;
CC         Note=Unprocessed;
CC       Name=Vacuolar ATP synthase catalytic subunit A;
CC         IsoId=P17255-2; Sequence=VSP_000002;
CC         Note=Mature;
CC       Name=Endonuclease PI-SceI;
CC         IsoId=P17255-3; Sequence=VSP_000001, VSP_000003;
CC         Note=Intein;
..
FT   INIT_MET      1      1       Removed.
FT   CHAIN         2    737       Intein-containing vacuolar ATP synthase
FT                                catalytic subunit A.
FT   REGION      284    737       Endonuclease PI-SceI.
FT   VAR_SEQ       2    283       Missing (in isoform Endonuclease PI-SceI).
FT                                /FTId=VSP_000001.
FT   VAR_SEQ     284    737       Missing (in isoform Vacuolar ATP synthase
FT                                catalytic subunit A).
FT                                /FTId=VSP_000002.
FT   VAR_SEQ     738   1071       Missing (in isoform Endonuclease PI-SceI).
FT                                /FTId=VSP_000003.

Example for ribosomal termination-reinitiation:

Current format:

CC   -!- MISCELLANEOUS: Translated by a ribosomal termination-reinitiation
CC       process from the bicistronic mRNA encoding for VP1 and VP2.

New format:

CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative initiation, Miscellaneous; Named isoforms=3;
CC       Name=Protein VP2; Synonyms=VP2;
CC         IsoId=Q672H9-1; Sequence=Displayed;
CC         Note=Produced by ribosomal termination-reinitiation at the end
CC         of VP1 ORF;
CC       Name=Uncharacterized protein VP3;
CC         IsoId=Q672I0-1; Sequence=External;
CC         Note=Produced by alternative initiation from the subgenomic RNA;
CC       Name=Subgenomic capsid protein; Synonyms=VP1;
CC         IsoId=Q672I1-2; Sequence=External;
CC         Note=Produced from the subgenomic RNA;

Not before: 15-Dec-2009

The CC line topic INTERACTION conveys information about binary protein-protein interactions. A description of its current format is available in the UniProtKB User Manual. Currently, all interaction data is automatically derived from the IntAct database. In the future, we will start to add manually curated binary protein-protein interactions to this topic (these are currently described in the CC line topic SUBUNIT). In order to represent isoform- and chain-specific interactions (e.g. for viral polyproteins) and to add interactor-specific comments (e.g. PTMs and binding regions), we are going to modify the format of the INTERACTION lines. Each binary interaction will be represented by a block of 3 to 4 lines:

• The first line of a block indicates the experimental evidence for the interaction, the source of the data (literature reference or By similarity) and, optionally, cross-reference(s) to other databases.
• The next line is an optional comment about the interaction.
• The last two lines give details on the interacting proteins: the Protein1= line represents the protein of the currently displayed entry, the Protein2= line the other interacting protein. If Protein2 is from a different organism than Protein1, its organism is indicated in an Organism= field.

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 (|). Special characters are escaped by a backslash (\).

 CC   -!- INTERACTION:
(CC       Interact=status \(source|By similarity\)( \(Potential\))?;( Xref=xref;)?
(CC         Comment=free_text;)?
 CC         Protein1=name [id(:ft_id)?];( Note=free_text;)?
 CC         Protein2=name( [id(:ft_id)?])?;( Organism=tax_name [NCBI_TaxID:tax_id];)?( Note=free_text;)?)+

• status = Yes | No
  Displays the experimental evidence for the interaction:
  • Yes if there is experimental evidence that the two proteins (or their orthologues) interact. An optional (Potential) qualifier indicates that the physiological relevance of the interaction is uncertain (e.g. the evidence results from a not further validated yeast-two-hybrid experiment).
  • No if there is experimental evidence that the two proteins do not interact under the experimental conditions described in the cited publication.
• source: Literature source for the interaction (PubMed or Ref).
• xref = db:db_id(, db:db_id)*
  List of database cross-references, each consisting of database name and unique database identifier. Currently, we only cross-reference the IntAct database.
• name: Biologically meaningful label or name for the protein.
  Displays the gene name (as shown in the GN line field Name= or OrderedLocusNames= or ORFNames=) or a dash '-' if the gene name is unknown.
  If the protein contains multiple chains (e.g. a viral polyprotein), the chain name (from the FT line) is displayed instead and the identifier which follows in square brackets must contain the FTId of the chain.
• id: UniProt accession number or isoform identifier (IsoId= field).
• ft_id: UniProt feature identifier (FTId= field).
• tax_name: Scientific name of the organism.
• tax_id: NCBI taxonomy database identifier of the organism.
• free_text: Free text.
  • Comment= contains additional information concerning the interaction (like subcellular location).
  • Note= contains additional information concerning the interacting protein (like PTM status, binding domains).

Examples:

CC   -!- INTERACTION:
CC       Interact=Yes (PubMed:11533489);
CC         Comment=HDAC3 mediates the deacetylation of RELA;
CC         Protein1=RELA [Q04206];
CC         Protein2=HDAC3 [O15379];

CC   -!- INTERACTION:
CC       Interact=Yes (Ref.4);
CC         Comment=Heterodimers are called polygalacturonase-1 (PG1);
CC         Protein1=GP1 [Q40161];
CC         Protein2=PG2 [P05117];

CC   -!- INTERACTION:
CC       Interact=Yes (PubMed:11501947) (Potential);
CC          Protein1=ABI3 [Q9P2A4];
CC          Protein2=ABI3BP [Q7Z7G0];

CC   -!- INTERACTION:
CC       Interact=Yes (By similarity);
CC         Protein1=GABRG2 [Q5REA1];
CC         Protein2=GABARAP;

CC   -!- INTERACTION:
CC       Interact=Yes (PubMed:10837489);
CC         Protein1=MCL1 [Q07820-1];
CC         Protein2=BAK1 [Q16611];
CC       Interact=Yes (PubMed:15901672, PubMed:17097560); Xref=IntAct:EBI-1003422,EBI-519866;
CC         Protein1=MCL1 [Q07820];
CC         Protein2=BAK1 [Q16611];

CC   -!- INTERACTION:
CC       Interact=Yes (PubMed:11418237); Xref=IntAct:EBI-375446,EBI-389883;
CC         Protein1=ABI1 [Q8IZP0];
CC         Protein2=NCK1 [P16333]; Note=SH3 1 domain;
CC       Interact=No (PubMed:12681507);
CC         Protein1=ABI1 [Q8IZP0-6];
CC         Protein2=NCK1 [P16333];
CC       Interact=Yes (By similarity);
CC         Protein1=ABI1 [Q8IZP0]; Note=N-terminus;
CC         Protein2=WASF1 [Q92558];

CC   -!- INTERACTION:
CC       Interact=Yes (PubMed:11086025);
CC         Protein1=C1QR1 [Q9NPY3];
CC         Protein2=Core protein p21 [P27958:PRO_0000037566)]; Organism=Hepatitis C virus genotype 1a (isolate H) [NCBI_TaxID=11108]; Note=See also other virus strains;

CC   -!- INTERACTION:
CC       Interact=Yes (PubMed:11086025);
CC         Protein1=Core protein p21 [P27958:PRO_0000037566)];
CC         Protein2=C1QR1 [Q9NPY3]; Organism=Homo sapiens [NCBI_TaxID=9606];

CC   -!- INTERACTION:
CC       Interact=Yes (PubMed:16470652); Xref=IntAct:EBI-907934,EBI-907894;
CC         Protein1=CNP [P06623];
CC         Protein2=CABP1 [Q9NZU7]; Organism=Homo sapiens [NCBI_TaxID=9606];