Binding Guidelines

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Background

As many terms in the Molecular Function ontology implicitly or explicitly imply the binding of a chemical or protein, it is unnecessary to co-annotate a gene product to a term from the binding node of GO to describe the binding of substrates or products that are already adequately captured in the definition of the Molecular Function term.

For instance, an enzyme MUST bind all of the substrates and products of the reaction it catalyzes. Similarly, a transporter MUST bind the molecules it transports. Therefore, as binding is implied, curators should avoid making redundant annotations.

Future ontology development efforts should be relied upon to improve the searching capability of any user using GO who is specifically interested in gene products carrying out a certain type of substrate/product binding.

There will be some cases, however, where it is appropriate to annotate a binding relationship. For example, published experiments may show that a gene product binds a non-hydrolyzable ATP analog, without demonstrating that it has ATPase activity. In such a case, it would be appropriate to annotate to GO:0005524 ATP binding using an IDA evidence code.

The GO is committed to ‘annotating to the experiment’. Therefore the curator should try to capture the specifics as much as feasible; use the binding term if the experiment shows binding directly, don’t use the binding term if the experiment shows catalysis, but not the specific binding activity.

The above paragraph indicates that curators will want to include additional information in their annotations where the definition of an associated Molecular Function term is unable to adequately describe the specific substrate/target being bound, and where the request of a more-specific Molecular Function term would be considered inappropriate.

Curators should use their judgment to decide whether the interaction is physiologically relevant and capture information relevant to the in vivo situation, not artificial substrates.

Examples: where GO term implies binding do not include target molecule in Column 8 (With) or Column 16

  • 1. C5: GO:0005524 ATP binding, do not add to C16 ChEBI ID for ATP
  • 2. C5: GO:0043559 insulin binding, do not add to C16 protein ID for insulin
  • 3. C5: GO:0017127 cholesterol transporter activity, do not add to C16 ChEBI ID for cholesterol

Examples: where GO term and/or definition implies binding but does not specify target molecule, therefore include protein ID in Column 8 (With) or other ID in Column 16

  • 1. C5: GO:0017046 peptide hormone binding, IPI, add to in Column 8 (With) protein ID for somatotropin
  • 2. C5: GO:0034041 sterol-transporting ATPase activity, add to C16 ChEBI ID for 7β-hydroxycholesterol (ABCG1, P45844, PMID:17408620)

Examples: only add to column 16 the direct target of the protein being annotated

  • 1. C5: GO:0004713 protein tyrosine kinase activity (function) add to C16 phosphophorylated 'target' protein ID, (has_input).
  • 2. C5: GO:0018108 peptidyl-tyrosine phosphorylation (process) add to C16 phosphophorylated 'target' protein ID, (has_input).
  • 3. C5: GO:0018108 peptidyl-tyrosine phosphorylation (process) do not add to C16 all the phosphorylated proteins detected if these are likely to include downstream targets.

Scope of binding terms in the GO

Chemical Binding

1. Annotations to GO:0008144 drug binding.UNRESOLVED

2. Ontology development needed to represent ATP binding always associated with a specific function, non-heme iron as cofactor or zinc-dependent alcohol dehydrogenases.RESOLVED Chris/Jane's new 'has part relationship' will address this issue

Protein Binding

1. Annotations to the protein binding terms should be maximally informative. Where possible the precise identity of the interacting protein should be captured in the 'with' field of an annotation. Similarly, usage of child terms that describe a particular class of protein binding (e.g. receptor tyrosine kinase binding) should be applied in preference to the parent term 'protein binding'; GO:0005515.

2. Scope of protein binding terms in GO: [[1], [2]) UNRESOLVED

3. protein C-terminus/ N-terminus binding [3] UNRESOLVED

Quality control checks now operational

1. No use of the 'NOT' qualifier with 'protein binding'; GO:0005515. This rule only applies to GO:0005515, children of this term can be qualified with NOT, as further information on the type of binding is then supplied in the GO Term e.g. NOT + 'GO:0051529 NFAT4 protein binding', would be fine, as the negative binding statement only applies to the NFAT4 protein.

2. Annotations to 'protein binding'; GO:0005515, should only be supplied with an evidence code where the interactor can be identified in the 'with' field. This rule only applies to GO:0005515, is not such a problem with child terms of protein binding where the type of protein is identified in the GO term name.

3. Reciprocal annotations for protein binding should be made This rule applies to GO:0005515 and it's descendants when the IPI evidence code is used

4. Annotations to 'protein binding' should not use the ISS evidence code This rule only applies to GO:0005515, is not such a problem with child terms of protein binding where the type of protein is identified in the GO term name.

For more details on quality control checks applied to 'protein binding'; GO:0005515 annotations, please see:

http://wiki.geneontology.org/index.php/Annotation_Quality_Control_Checks