- 1 Definition
- 2 Range
- 3 Child Terms
- 4 Usage guidance
- 5 Specific cases
- 6 Quality Control Checks
- 7 Relations Ontology
- 8 Review Status
A gene product is associated with a GO Molecular Function term using the qualifier 'contributes_to' when it is a member of a complex that is defined as an irreducible molecular machine' - where a particular Molecular Function cannot be ascribed to an individual subunit(s) of a complex.
The 'contributes_to' qualifier can only be used with GO Molecular Function terms.
- The 'contributes_to' qualifier is used only in cases where a gene product does not perform a molecular function on its own. Being part of a complex is not sufficient to use this qualifier.
- 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'.
1. 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. Annotation for ATP citrate lyase subunit 1:
Object: UniProt:Q8KDG1 (CT1089) Relation: contributes_to GO term: GO:0003878 ATP citrate synthase activity Evidence code: IDA PMID:16952946
2. 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. Annotation for S. pombe RNA polymerase II large subunit Rpb1:
Object: SPBC28F2.12 Relation: contributes_to GO term: GO:0001055 RNA polymerase II activity Evidence code: EXP PMID:9325316
3. MBF transcription factor complex: res2 and cdc10 are both members of the Schizosaccharomyces pombe MBF transcription factor complex. Each contains, by sequence analysis, a predicted DNA-binding domain. In vitro assays, however, show that neither subunit binds DNA alone; DNA-binding activity is only detectable when the subunits are co-expressed. In this case, res2 and cdc10 are both annotated to GO:0000978 ‘RNA polymerase II cis-regulatory region sequence-specific DNA binding ’ using the ‘contributes to’ qualifier. Annotation for res2 MBF complex subunit:
Object: PomBase:SPAC22F3.09c (res2) Relation: contributes_to GO term: GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding Evidence code: IDA PMID:7926774
Multi-subunit complex in which the subunit necessary to perform the molecular function is not (yet) known
- 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'.
- Need examples.
When NOT to use 'contributes_to': 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 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". The molecular function annotations should have the extension 'occurs_in' eIF2 complex (GO:0005850), and all three are part_of the cellular component eIF2 complex (GO:0005850).
- 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 to GTPase activity 
- STT3 : "dolichyl-diphosphooligosaccharide-protein glycotransferase activity": although it is a member of a complex, it is the catalytic subunit, so it should be annotated without 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 .
- Therefore, only PIGM is annotated to GO:0000030 mannosyltransferase activity, without '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.
Other common functions for protein complex members:
- 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.
- Need examples.
- If a gene product is shown to bring together either a subunit of the complex with another protein, a substrate, a membrane, etc., this gene product may be anotated to GO:0060090 molecular adaptor activity or an appropriate child term.
- Need examples.
Quality Control Checks
- if and only if exists c', p' c part_of c' and c' capable_of p and c capable_of p' and p' part_of p then c contributes_to p [RO]
Last reviewed: January 30, 2020