Contributes to

Overview

Usage guidance

  Based on https://github.com/geneontology/go-annotation/issues/1650#issuecomment-499620635
  To review with Kimberly 

Some molecular functions require more than one gene product to be accomplished. The gene products required for those molecular function are part of the same protein-containing complex.

Single catalytic subunit

Being part of a complex does not mean that the activity necessarily requires multiple subunits: if a single subunit performs the activity, annotate the gene product to this function without any qualifier. Use the relation 'enables (Protein2GO)/enabled by (Noctua)' to annotate the molecular function. If the gene product forms homomultimers annotate directly to the MF as it's usually very difficult to ascertain if only the multimer has the MF or also the monomer.

Multiple catalytic subunits

If a complex requires multiple subunits for activity, annotate all subunits known to acontribute to the activity with the 'contributes_to' qualifier.

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.

• • • Optionally, place the CP AC in the AE with qualifier occurs_in. ?????
• Also annotate the complex subunits to 'GO:0032991 protein-containing complex' or an appropriate child term.

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'.

• • • Optionally, place the CP AC in the AE with qualifier occurs_in. ?????
• Also annotate the complex subunits to 'GO:0032991 protein-containing complex' or an appropriate child term.

Regulatory subunits

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

• • • Optionally, place the CP AC in the AE with qualifier occurs_in. ?????

Adaptor activity

• • • I dont think this is the definition I'd give it ???

If a gene product has been identified as a crucial part of the complex without catalytic or regulatory activity, annotate to "GO:0060090 molecular adaptor activity" or children if appropriate.

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.

• • • Optionally, place the CP AC in the AE with qualifier occurs_in. ?????

Child Terms

None

Examples of Usage

Multi-subunit complexes in which the catalytic subunit 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 catalytic subunit

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 catalytic subunit is not (yet) known

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

• Need examples.

When NOT to Use 'contributes to'

• 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.

Relations Ontology

contributes to

Review Status

Last reviewed: October 22, 2019

Back to: Annotation Relations