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#11816 APC complexed with inhibitor
Following on from a discussion with Tanya and Antonia....
The APC is inhibited by various CDC20/fizzy family inhibitors at various cell cycle phases (not clear cut, sometimes overlapping).
Our first question is how to represent these complexes.
- Do we request a complex
APC-Cdc20
APC-fizzy related (there is a precedent for this, but there are various fizzy related proteins so it is difficult to establish each complex version without using the gene names
APC-Srw1 complex, APC-Mfr1 etc)
- Alternatively as this is a complex inhibitor, we could annotate this as
APC -complex binding.
(IN which case we would obsolete the existing APC-inhibitor complex terms)
One advantage of 2 is that we would not need to ensure that all 15 APC subunits were annotated to all complexes, and we would not have the difficulties defining the complexes which do not seem to be exactly conserved in their role between species.
However, if people would expect to see these annotated as a complex in their own right we should do 1.
If we decide to do 1. we will need a better way to describe the various permutations (I can't think of anything easily without including gene product names we would not easily be able to distinguish the specific variations.
Diff:
Assigning to Tanya.
Or we create the specific complexes in the complex portal as children of the generic 'APC inhibitor complex' term, then you have unique IDs for annotation... Making 15 different complexes that just differ by their 'fizzy-related' protein is no big deal as long as we have some evidence for their existence :)
Looks like we already have a bunch of APC variants in the CP:
http://www.ebi.ac.uk/intact/complex/?q=apc
Birgit
In this case do we need some rules how to name the organism specific variants?
For example, pombe appears to have 2 copies of the human FZR1/ cerevisiae CDH1
which have possibly split the roles of the orthologous complexes at different point in the cell cycle. We have an identical problem with the CDK-cyclin complexes.
For APC-related and Cdk-cyclin complexes the sensible way to classify them seems to be by the specific cell cycle transitions they are regulating (i.e their functional role) rather than:
i) the 'families' they belong to seem to be somewhat 'swapped around'.
For instance a cyclin which operates at G1 in one organism, its ortholog may operate at a different transition or even cycle (mitotic vs meiotic) in another organism
or
ii) the specific substrates of the complexes (because the substrates are likely to be partly but not fully conserved between species, and you are unlikely to know all the substrates)
This way an database would only need to request new species specific instances of these complexes if they had 2 complexes operating at the same transition and needed to make a distinction between them (for instance to make links between their complex instance, and specific substrates)
An aside:
Maybe we could look at these two sets of complexes as a mini-project? They are really important cellular components with a lot of literature, but not very well annotated in GO.
For example, Cdk1 has the highest centrality and connectivity of any protein in a unicellular eukaryotic network (possibly even in multicellular) but only 73 proteins experimentally annotated to the CDK complex terms in GO, and all but 13 are to the generic term!)
The variation to the role in the cell cycle adds indeed a further complication. It's no problem for the CP as we just annotate whichever process and function is applicable to the particular complex. We'd name them by subunit composition (I'd change them from using simply 'variant x' to make them distinguishable in the list of results). The only question then is: which should be the most granular GO term for these complexes? Which goes back to Val's question above. Do we make the subunit-specific complexes in GO as well or just functional complexes based on which cell cycle phase they act in with subunit composition names as narrow synonyms?
David OS is working on this and might want to comment.
Birgit
(will copy to GH as well)