---
layout: rule
id: GORULE:0000005
title: "IEA, ISS, ISO, ISM, ISA, IBA, RCA annotations ae not allowed for direct annotations to to 'protein binding ; GO:0005515 or GO:0005488 binding''"
type: report
fail_mode: soft
status: implemented
contact: "go-quality@lists.stanford.edu"
implementations:
  - language: java 
    source: https://github.com/owlcollab/owltools/
---

This rule only applies to direct annotations to GO:0005515 and GO:0005488 (GAF column 5, GAPD column 4), 
Annotations to descendant terms such as mitogen-activated protein kinase p38 binding ; GO:0048273 are allowed, since the GO term name contains 
specific information describing the identity of the interactor.

The following evidence codes (GAF column 7, GPAD column 6) are not allowed: IEA, ISS, ISM, ISO, ISA, IBA.

If we take an example annotation:

gene product: protein A\
GO term: protein binding ; GO:0005515\
evidence: IPI\
reference: PMID:123456\
with/from: **with** protein A

this annotation line can be interpreted as: protein A was found to carry
out the 'protein binding' activity in PMID:12345, and that this function
was Inferred from the results of a Physicial Interaction (IPI) assay,
which involved protein X

However if we would like to transfer this annotation to protein A's
ortholog 'protein B', the ISS annotation that would be created would be:

gene product: protein B\
GO term: protein binding ; GO:0005515\
evidence: ISS\
reference: GO\_REF:curator\_judgement\
with/from: **with** protein A

This is interpreted as 'it is inferred that protein B carries out
protein binding activity due to its sequence similarity (curator
determined) with protein A, which was experimentally shown to carry out
'protein binding'.

Therefore the ISS annotation will not display the the interacting
protein X accession. Such an annotation display can be confusing, as the
value in the 'with' column just provides further information on why the
ISS/IPI or IGI annotation was created. This means that an ISS projection
from protein binding is not particularly useful as you are only really
telling the user that you think an homologous protein binds a protein,
based on overall sequence similarity.



For more information, see the [binding
guidelines](http://wiki.geneontology.org/index.php/Binding_Guidelines)
on the GO wiki.