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Source ontology files for the Gene Ontology
http://geneontology.org/page/download-ontology
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PKC/calcium-dependent protein serine/threonine kinase activity: 3 terms have the same meaning #25457

Open pgaudet opened 1 year ago

pgaudet commented 1 year ago

GO:0004698 calcium-dependent protein kinase C activity GO:0009931 calcium-dependent protein serine/threonine kinase activity GO:0010857 calcium-dependent protein kinase activity

all mean the same thing.

GO:0004698 has an EC mapping (2.7.11.1); others dont. The most accurate and informative label is 'calcium-dependent protein serine/threonine kinase activity'

Annotations are here: https://github.com/geneontology/go-annotation/issues/4597

2 of these terms should be obsoleted and replaced by the third one.

Thanks, Pascale

deustp01 commented 1 year ago

Are you saying that all calcium-dependent protein kinases are in fact specifically calcium-dependent protein serine/threonine kinases (GO:0009931), so annotations to GO:0004698 (we have 1) and GO:0010857 (we have 3) should be made to GO:0009931 instead? Don't know the details of protein kinase classes, so this is sanity check to be sure that this is the biologically correct re-annotation - it looks like a gain in information / specificity if we can safely do it.

Thanks

pgaudet commented 1 year ago

Hi @deustp01 Thanks for bringing that up. I compared all proteins annotated to these 3 terms to Panther family names and EC assignments by UniProt, see https://docs.google.com/spreadsheets/d/16GlE7inJ5V4-4_dPdGrCzpVRplC_oegV1DZ2afaADEE/edit#gid=0

and all but one were ser/thr kinases (the other one was a chemokine, this was a mistake in the annotation, which I have mow removed).

So "merging" (ie obsoleting with replaced_by) these 3 terms seem correct.

Thanks, Pascale

raymond91125 commented 1 year ago

GO:0004698 calcium-dependent protein kinase C activity has XREF EC 2.7.11.13 (also XREF by GO:0004697, GO:0004699), which is protein kinase C that can be calcium dependent or independent. https://enzyme.expasy.org/EC/2.7.11.13 PKC has three categories, depending on their requirements for Ca2+, DAG, and phospholipid for activation. https://en.wikipedia.org/wiki/Protein_kinase_C. So perhaps calcium-dependent protein kinase C activity refers to "conventional - require DAG, Ca2+, and phospholipid for activation". Furthermore, there are calcium/calmodulin-dependent protein (CaM) kinases in the annotation table. They are not PKC.

pgaudet commented 1 year ago

Right, thanks @raymond91125 , I truncated the EC - so this is what we have

image

I think these 5 terms are the same:

GO:0004699 | calcium-independent protein kinase C activity GO:0004698 | calcium-dependent protein kinase C activity GO:0004697 | protein kinase C activity GO:0010857 | calcium-dependent protein kinase activity GO:0009931 | calcium-dependent protein serine/threonine kinase activity

Thanks, Pascale

deustp01 commented 1 year ago

I think these 5 terms are the same

Not sure. Here is the IUBMB comment for EC 2.7.11.13:

A family of serine- and threonine-specific protein kinases that depend on lipids for activity. They can be activated by calcium but have a requirement for the second messenger diacylglycerol. Members of this group of enzymes phosphorylate a wide variety of protein targets and are known to be involved in diverse cell-signalling pathways. Members of the protein kinase C family also serve as major receptors for phorbol esters, a class of tumour promoters.

It looks like EC has chosen to group protein kinases together regardless of their dependence on calcium (because the reaction mechanism is the same in all cases?) but it is still biologically important to distinguish the dependent and independent ones, so this may be a case where more that one GO term properly maps to a single EC term?

pgaudet commented 1 year ago

Thanks for pointing that out. It's a bit odd then - calcium-independent PKC then a serine/threonine protein kinase, right ? We would not group MFs by the protein family they belong to...

@raymond91125 what are your thoughts on this?

raymond91125 commented 1 year ago

@pgaudet Sorry, I'm not sure what the goal is now. If we merge the 5 terms above, what should we call it? PKC is not necessarily calcium dependent. Also, we are then mixing activities with different activating mechanisms together, is that desirable?

raymond91125 commented 1 year ago

Some calcium-activated protein kinases may be of tyrosine PMID:26150074, that fact distinguishes calcium-dependent protein kinase activity from calcium-dependent protein serine/threonine kinase activity. Thus it seems that all 5 of these terms are distinct (or grouping for more than one child) and perhaps should not be merged.

pgaudet commented 1 year ago

Are you sure this is the same activity? This is what UniProt has for PTK2B (https://www.uniprot.org/uniprotkb/Q14289/entry)

Activated in response to stimuli that lead to increased intracellular Ca2+ levels; this activation is indirect and may be mediated by calcium-mediated production of reactive oxygen species (ROS).

And PTK2B is annotated to EC:2.7.10.2.

Thanks, Pascale

raymond91125 commented 1 year ago

This could be outdated. "Although the mechanism of activation of Pyk2 is not known in detail, the FERM domain has been suggested to mediate Ca2+/CaM-dependent Pyk2 homodimerization (via binding of CaM to the α2-helix of the F2 subdomain) and transphosphorylation at Tyr402 to recruit Src, which binds via its SH2 domain and phosphorylates Pyk2 at Tyr579 and Tyr580 within the activation loop of the kinase domain to generate maximal Pyk2 activity (Kohno et al. 2008)."

raymond91125 commented 1 year ago

My point is that if we merge these terms, we may have to reverse the merge, whereas not merging them does not seem to cause significant harm.

pgaudet commented 1 year ago

I'll bring this up on a signaling cassettes call.

Thanks, Pascale

pgaudet commented 1 year ago

Proposal:

raymond91125 commented 1 year ago

The atypical PKCs do not depend on DAG. https://en.wikipedia.org/wiki/Protein_kinase_C, https://www.alliancegenome.org/gene/HGNC:9412

raymond91125 commented 1 year ago

I suggest that we make things simple and less granular.

  1. Merge calcium-dependent protein kinase C activity and calcium-independent protein kinase C activity into protein kinase C activity, EC:2.7.11.13
  2. The only IS_A parent for the solo protein kinase C activity is protein serine/threonine kinase activity. This follows the EC hierarchy, 2.7.11.-: Protein-serine/threonine kinases.
  3. We can leave calcium-dependent protein kinase activity and calcium-dependent protein serine/threonine kinase activity intact.
pgaudet commented 1 year ago

The atypical PKCs do not depend on DAG. https://en.wikipedia.org/wiki/Protein_kinase_C, https://www.alliancegenome.org/gene/HGNC:9412

Right, on Monday we were proposing to annotate these to the parent, since, as pointed out in wikipedia,

atypical (a)PKCs (including protein kinase Mζ and ι / λ isoforms) require neither Ca2+ nor diacylglycerol for activation.The term "protein kinase C" usually refers to the entire family of isoforms.

GO does not capture protein families.

raymond91125 commented 1 year ago

Maybe I'm not getting the correct source but I thought EC:2.7.11.13 covers the atypical ones. https://www.ebi.ac.uk/intenz/query?cmd=SearchID&id=16301&view=INTENZ

cmungall commented 1 year ago

EC:2.7.11.13 is used to annotate the atypical ones, so as GO doesn't represent protein families the mapping between the GO term and EC has to be inexact to prevent incorrect propagation

raymond91125 commented 1 year ago

CDPK1 https://amigo.geneontology.org/amigo/gene_product/UniProtKB:Q7XZK5 is not a PKC but a calcium-dependent, calmodulin-independent protein S/T kinase PMID:22760783

pgaudet commented 4 months ago

Hello again,

Looking at that once again, and I came to the same conclusion - all calcium-dependent PK are ser/thr. If we find a real example of Tyr kinase that is calcium-dependent, we can create this term as a child of tyrosine kinase. GO:0010857 calcium-dependent protein kinase activity is an unnecessary grouping term.

I will obsolete GO:0010857 calcium-dependent protein kinase activity is an unnecessary grouping term & replace by its child GO.0009931 calcium-dependent protein serine/threonine kinase activity.

Thanks, Pascale

pgaudet commented 4 months ago

Dear all,

The proposal has been made to obsolete GO:0010857 calcium-dependent protein kinase activity is an unnecessary grouping term & replace by its child GO.0009931 calcium-dependent protein serine/threonine kinase activity.

There are no mappings; there are 8 EXP annotations to this term that will be automatically replaced, see https://github.com/geneontology/go-annotation/issues/5324

You can comment on the ticket: https://github.com/geneontology/go-ontology/issues/25457

Thanks, Pascale

pgaudet commented 4 months ago

Add do_not_annotate to diacylglycerol-dependent serine/threonine kinase activity?

Wait for reviews here: https://github.com/geneontology/go-annotation/issues/5327

raymond91125 commented 4 months ago

Please re-assign this to me if needed. Thanks.