Contributes to

Overview

Definition

A gene product can be associated with a GO Molecular Function term using the qualifier 'contributes_to' when it is a member of a complex that plays an active role in a molecular function, but cannot perform the function on its own.

Range

The 'contributes_to' qualifier can only be used with GO Molecular Function terms.

Child Terms

None

Usage guidance

• The 'contributes_to' qualifier is used differently depending on whether a gene product is
• The molecular function annotation for any member of a stable complex should have the extension 'occurs_in' 'GO:0032991 protein-containing complex' or an appropriate child term.
• In all cases, all intrinsic members of a complex should be annotated to 'part of' some 'GO:0032991 protein-containing complex' or an appropriate child term.

Multiple subunits required for a molecular function

• If multiple subunits participate in the molecular function, annotate all participating subunits to the activity using the 'contributes_to' qualifier.
• For example, if a gene product is part of a complex but only has the function as part of that complex, e.g. forms a composite binding site that is required for the function, annotate to the molecular function using the qualifier 'contributes_to'.

Unknown contributing subunits

• If a gene product is part of a complex and it is unknown which subunit is responsible for the activity of the complex, annotate all gene products to the molecular function using the qualifier 'contributes_to'.

Unknown role

If a gene product has been identified as an integral part of a complex but its role is uncharacterized (no evidence for catalytic, regulatory or adaptor role), annotate to MF root term (GO:0003674 molecular_function) or do not annotated at all to MF.

When NOT to use 'contribute_tso': single subunit required for a molecular function

• Being part of a complex does not mean that the molecular function necessarily requires multiple subunits: if a single subunit performs the molecular function, annotate the gene product to this function without any qualifier, but using relation 'enables (Protein2GO) or enabled by (Noctua)'.
• If the gene product forms homomultimers, also annotate the gene product to this function without any qualifier.

Examples

• Prkag1 (protein kinase AMP-activated non-catalytic subunit gamma 1) RGD:3388: PMID:21399626 shows that the activation loop of the kinase domain is stabilized by the regulatory domain. The paper also shows that the regulatory subunit binds ADP, so it is really the subunit with a regulatory role.
  • annotation should be to "GO:0019887 protein kinase regulator activity"; Prkag1 does NOT contribute to "AMP-activated protein kinase activity".
• Prkaa1 (protein kinase AMP-activated catalytic subunit alpha 1) RGD:3387 is the active subunit; is should be annotated to "AMP-activated protein kinase activity", without the "contributes_to" qualifier.

Specific cases

Regulatory subunits

• If a gene product has been identified as the regulatory subunit of a complex, annotate to "X regulator activity" (GO:0098772 molecular function regulator or a child). Use 'has input' some 'gene product' to describe which gene product the annotated gene product regulates.

Examples of Usage

Multi-subunit complexes in which the molecular function is known or predicted

Annotate the catalytic subunit, without the contributes_to qualifier.

• eIF2: has three subunits (alpha, beta, gamma); one binds GTP; one binds RNA; the whole complex binds the ribosome (all three subunits are required for ribosome binding). So one subunit is annotated to GTP binding and one to RNA binding without qualifiers, and all three stand in the contributes_to relationship to "ribosome binding". And all three are part_of an eIF2 complex.

• • eIF2gamma is the actual GTPase, and eIF2alpha and -beta serving accessory functions. Therefore, eIF2gamma is annotated to GTPase activity; the alpha and beta subunits are not annotated at all to GTPase activity [1]

• STT3 [2]: "dolichyl-diphosphooligosaccharide-protein glycotransferase activity": although it is a member of a complex, it is the catalytic subunit, so it should not be annotated with the "contributes_to" qualifier.

• PIGM-PIGX complex: The PIGM-PIGX complex catalyzes GO:0000030 mannosyltransferase activity. PIGM is the sole catalytic subunit, and while the accessory PIGX subunit is required for activity, it does not have the activity [3].
  • Therefore, only PIGM is annotated to GO:0000030 mannosyltransferase activity, without 'contributes_to'.

Multi-subunit complexes in which there is no single subunit responsible for the molecular function

Annotate all subunits, with the contributes_to qualifier.

• ATP citrate lyase (ACL) in Arabidopsis: it is a heterooctamer, composed of two types of subunits, ACLA and ACLB in a A(4)B(4) stoichiometry. Neither of the subunits expressed alone give ACL activity, but co-expression results in ACL activity. Both subunits contribute_to the ATP citrate lyase activity. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1595482)

• Subunits of nuclear RNA polymerases: none of the individual subunits have RNA polymerase activity, yet all of these subunits contribute_to DNA-dependent RNA polymerase activity. Note that there are gene products that are members of a nuclear RNA polymerase complex that serve other functions besides the polymerase activity. In these cases, the subunits would not be annotated to polymerase activity using the 'contributes to' qualifier.

Multi-subunit complexes in which the subunit necessary to perform the molecular function is not (yet) known

Annotate all subunits, with the contributes_to qualifier until further characterization of the subunits is established.

• Need examples.

Relations Ontology

contributes to

Review Status

Last reviewed: January 30, 2020

Back to: Annotation Relations