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Change of annotation topic 'Interaction'

Not before April 22, 2020

The annotation topic ‘Interaction’ provides information about binary protein-protein interactions. This data is curated in the IntAct database and a quality-filtered subset is imported into UniProtKB at each release.

In the context of improving the functional annotation of different gene products in UniProtKB/Swiss-Prot, we are going to import more detailed data from IntAct. Our current representation of a binary protein-protein interaction provides details only for the protein that is described in another entry. This leaves ambiguity in UniProtKB/Swiss-Prot entries that describe more than one protein (isoforms or/and products of proteolytic cleavage). To address this we are going to describe both interacting proteins by unique UniProtKB identifiers.

This change will affect the three main UniProtKB distribution formats (text, XML, RDF). The details are described for each format in a separate section below. The following placeholders are used in the format descriptions:

  • <Interactant> represents a UniProtKB protein.
    • <Accession> is a UniProtKB accession number.
    • <IsoId> is a UniProtKB isoform ID.
    • <ProductId> is a UniProtKB product ID.
    • <Gene> is either the gene name, ordered locus name or ORF name of the gene that encodes the UniProtKB protein (see Gene names).
  • <Experiments> is the number of experiments in IntAct that support an interaction.
  • <IntActId> is an IntAct protein ID.

Note: The format descriptions make use of POSIX ERE syntax.

Text format

Current format:

CC   -!- INTERACTION:
CC       <Interactant>( \(xeno\))?; NbExp=<Experiments>; IntAct=<IntActId>, <IntActId>;
CC       <Interactant>( \(xeno\))?; NbExp=<Experiments>; IntAct=<IntActId>, <IntActId>;
CC       ...

The <Interactant> is described in the following way:

Self|(<Accession>|<IsoId>):(<Gene>|-)

Where Self represents a self-interaction and a dash is shown for proteins with an undefined <Gene>. 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.

New format:

CC   -!- INTERACTION:
CC       <Interactant>; <Interactant>;( Xeno;)? NbExp=<Experiments>; IntAct=<IntActId>, <IntActId>;
CC       <Interactant>; <Interactant>;( Xeno;)? NbExp=<Experiments>; IntAct=<IntActId>, <IntActId>;
CC       ...

Where

  • the first <Interactant> is represented by:
    (<Accession>|<IsoId>|<ProductId>)
    
  • the second <Interactant> is represented by:
    (<Accession>|<IsoId>|<ProductId> \[<Accession>\])(: <Gene>)?
    

Example: P11309

Binary interactions with different isoforms that are described in P11309.

Current format:

CC   -!- INTERACTION:
CC       Q9BZS1-1:FOXP3; NbExp=3; IntAct=EBI-1018629, EBI-9695448;
CC       Q9UNQ0:ABCG2; NbExp=5; IntAct=EBI-1018633, EBI-1569435;

New format:

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;

Example: P27958 and Q9NPY3

Binary interaction with a product of proteolytic cleavage. Interactions involving products of proteolytic cleavage are currently not imported from IntAct, therefore only the new data/format is shown.

New data and format of P27958:

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

New data and format of Q9NPY3:

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

XML format

The UniProtKB XSD represents a binary interaction with:

  • two interactant elements of interactantType
  • a boolean organismsDiffer element 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.
  • an experiments element that gives the number of experiments in IntAct that support an interaction.

The interactantType uses an interactantGroup to represent a sequence of:

  • an id element
  • an optional label element

We are going to add an optional dbReference element to the interactantGroup to allow us to represent the UniProtKB <Accession> for a <ProductId>:

    <xs:group name="interactantGroup">
        <xs:sequence>
            <xs:element name="id" type="xs:string"/>
            <xs:element name="label" type="xs:string" minOccurs="0"/>
            <xs:element name="dbReference" type="dbReferenceType" minOccurs="0"/>
        </xs:sequence>
    </xs:group>

Current format:

<comment type="interaction">
  <interactant intactId="<IntActId>"/>
  <interactant intactId="<IntActId>">
    <id><Accession>|<IsoId></id>
    <label><Gene></label>
  </interactant>
  <organismsDiffer>true|false</organismsDiffer>
  <experiments><Experiments></experiments>
</comment>

New format:

<comment type="interaction">
  <interactant intactId="<IntActId>">
    <id><Accession>|<IsoId>|<ProductId></id>
  </interactant>
  <interactant intactId="<IntActId>">
    <id><Accession>|<IsoId>|<ProductId></id>
    <label><Gene></label>
    <!-- If <id> is a <ProductId>: -->
    <dbReference type="UniProtKB" id="<Accession>"/>
  </interactant>
  <organismsDiffer>true|false</organismsDiffer>
  <experiments><Experiments></experiments>
</comment>

Example: P11309

Binary interactions with different isoforms that are described in P11309.

Current format:

<comment type="interaction">
  <interactant intactId="EBI-1018629"/>
  <interactant intactId="EBI-9695448">
    <id>Q9BZS1-1</id>
    <label>FOXP3</label>
  </interactant>
  <organismsDiffer>false</organismsDiffer>
  <experiments>3</experiments>
</comment>
<comment type="interaction">
  <interactant intactId="EBI-1018633"/>
  <interactant intactId="EBI-1569435">
    <id>Q9UNQ0</id>
    <label>ABCG2</label>
  </interactant>
  <organismsDiffer>false</organismsDiffer>
  <experiments>5</experiments>
</comment>

New format:

<comment type="interaction">
  <interactant intactId="EBI-1018629">
    <id>P11309-1</id>
  </interactant>
  <interactant intactId="EBI-9695448">
    <id>Q9BZS1-1</id>
    <label>FOXP3</label>
  </interactant>
  <organismsDiffer>false</organismsDiffer>
  <experiments>3</experiments>
</comment>
<comment type="interaction">
  <interactant intactId="EBI-1018633">
    <id>P11309-2</id>
  </interactant>
  <interactant intactId="EBI-1569435">
    <id>Q9UNQ0</id>
    <label>ABCG2</label>
  </interactant>
  <organismsDiffer>false</organismsDiffer>
  <experiments>5</experiments>
</comment>

Example: P27958 and Q9NPY3

Binary interaction with a product of proteolytic cleavage. Interactions involving products of proteolytic cleavage are currently not imported from IntAct, therefore only the new data/format is shown.

New data and format of P27958:

<comment type="interaction">
  <interactant intactId="EBI-6377335">
    <id>PRO_0000037566</id>
  </interactant>
  <interactant intactId="EBI-1755002">
    <id>Q9NPY3</id>
    <label>CD93</label>
  </interactant>
  <organismsDiffer>true</organismsDiffer>
  <experiments>2</experiments>
</comment>

New data and format of Q9NPY3:

<comment type="interaction">
  <interactant intactId="EBI-1755002">
    <id>Q9NPY3</id>
  </interactant>
  <interactant intactId="EBI-6377335">
    <id>PRO_0000037566</id>
    <dbReference type="UniProtKB" id="P27958"/>
  </interactant>
  <organismsDiffer>true</organismsDiffer>
  <experiments>2</experiments>
</comment>

RDF format

The UniProt RDF schema ontology represents a binary interaction with an interaction property whose rdfs:range is the Interaction class. This class is the domain of the following properties that describe the interaction:

  • xeno is a boolean 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.
  • experiments gives the number of experiments in IntAct that support an interaction.

A Participant is identified by its unique IntAct identifier. It also refers to the corresponding UniProtKB protein which is represented as described in Functional annotation of different gene products in UniProtKB/Swiss-Prot. An optional rdfs:label property may provide the gene name, ordered locus name or ORF name of the gene that encodes the UniProtKB protein.

The RDF schema ontology requires no changes to represent the more detailed data that will be imported from IntAct. Due to the symmetry of binary interactions, the UniProt SPARQL server already provides access to the full details about both interacting proteins. We will however take this opportunity to normalize the URI of a binary interaction so that the two UniProtKB entries that describe the interacting proteins refer to the interaction with the same URI:

Current format:

<<Accession>#interaction-<IntActId>-<IntActId>> .

New format:

<http://purl.uniprot.org/intact/<IntActId>-<IntActId>> .

Example: P11309 and Q8N9N5

Current format:

P11309:

<P11309#interaction-696621-744695>

Q8N9N5:

<Q8N9N5#interaction-744695-696621>

New format:

P11309 and Q8N9N5:

<http://purl.uniprot.org/intact/EBI-696621-EBI-744695>
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