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Binding Term Documentation
From the Documentation for the Function Ontology
Avoid Binding Relationships
Catalytic activities should not be related to binding terms (see the September 2003 Bar Harbor GO meeting minutes); for example, ATPase activity should not be related to ATP binding. Similarly, there should not be a relationship between transporter terms and binding terms. Binding terms should only be used in cases where a stable binding interaction occurs. There are several reasons for this.
Firstly, transporter, catalysis and binding activities are all in the function ontology, which is used to describe elemental single step activities that occur at the macromolecular level. That means that if we were to further subdivide these functions - for example, splitting the catalysis of a reaction into steps such as "substrate binding", "formation of unstable intermediate" or "attraction of electrons to positive charge" - we would be saying that a reaction was actually a series of functions - i.e. a process. Additionally, we would be going beyond the scope of the molecular function ontology as we would be dealing with events on a molecular or atomic level.
Another reason is the sheer practicality of sorting through the 4000+ catalytic reactions we have in GO and deciding which of the substrates and products should be given 'binding' terms. Should we say that only substrates are bound by an enzyme? How about reversible reactions or cases where the reaction mechanism is unknown?
Finally, the GO binding terms are supposed to represent stable binding interactions, as opposed to the transient binding that occurs prior to catalysis. Hence there should not be a connection between stable binding and catalysis.
From the minutes of Bar Harbor GO Consortium Meeting in 2003
Section 5) Ontology Development Issues
d) Consistency of Parentage (catalysis and binding) Amelia: catalysis and binding - sometimes an enzyme activity has parents of both the catalysis term and binding term. Mostly there is only the catalysis parent. Which way should it be? Consensus: enzyme activities should have only the catalysis parent. [Action Item 17.Remove all binding parents to enzyme activities where appropriate. Document the fact that binding is not always a parent of enzyme. Binding only when stable binding occurs]
Ontology Development Action Items 17. Document the fact that binding is not always a parent of enzyme. Binding is only a parent when stable binding occurs. Remove Binding as parent where appropriate.
From AMIGO: Accession GO:0016887 Ontology molecular function Synonyms
related: complex V (mitochondrial electron transport) related: SV40 T-antigen narrow: (Ca2+ + Mg2+)-ATPase narrow: HCO3--ATPase alt_id: GO:0004002 exact: adenosine 5'-triphosphatase activity exact: adenosine triphosphatase activity exact: adenosinetriphosphatase activity exact: ATP hydrolase activity exact: ATP monophosphatase activity exact: ATP phosphohydrolase activity
Definition Catalysis of the reaction: ATP + H2O = ADP + phosphate. May or may not be coupled to another reaction. [source: EC:188.8.131.52, GOC:jl]
Comment: Consider also annotating to the molecular function term 'ATP binding ; GO:0005524'.
Other items from agenda
- using 'binding' for annotation
- should it be used in cross product annotations (Jim) (see Annotation_Cross_Products#binding_example)
- transfer of 'binding' term annotations via ISS/ISO??
Issue 1: Catalytic activities
The GO documentation says that Catalytic activities should not be related to binding terms (see the September 2003 Bar Harbor GO meeting minutes); for example, ATPase activity should not be related to ATP binding.
This is counterintuitive to most annotators, who think evidence that a protein has ATPase activity is evidence that it binds ATP.
- Allow annotation to binding based on catalytic activity
- Leave annotation policy as is and do more "advertising" about how to correctly annotate binding. This includes removing confusing suggestions in AmiGO (see below).
From AMIGO: Accession GO:0016887 Ontology molecular function Definition Catalysis of the reaction: ATP + H2O = ADP + phosphate. May or may not be coupled to another reaction. [source: EC:184.108.40.206, GOC:jl] Comment: Consider also annotating to the molecular function term 'ATP binding ; GO:0005524'.
Issue 2: Transporters
(Pascale) Should transporters be annotated to the substrates they transport? According to the documentation, no. Which means that transporters are annotated to function = x transporter activity and process = x transport. Is this correct? Should we make an automated check that would ensure that if something is annotated to x transport it is not annotated to x binding?
Issue 3: Inconsistencies within the GO
(Pascale) Some binding terms do not exist in the function ontology: drug binding, toxin binding, pigment binding; are there rules as to what types of binding we want to capture?
Issue 4: Relationship between function and xx binding
If a gene product is annotated to xx binding, should this be physiologically significant with respect to that gene product? For example a gene product can bind another gene product or a molecule either for regulation of activity, as a substrate, as a cofactor, etc, etc, etc.