Open ValWood opened 10 months ago
revised def from A complex that is capable of kinase activity directed towards the C-terminal Domain (CTD) of the largest subunit of RNA polymerase II to A complex that is capable of cyclin-dependent kinase activity directed towards the C-terminal Domain (CTD) of the largest subunit of RNA polymerase II
I'm a bit confused what cyclin-dependent protein kinase activating kinase holoenzyme complex (GO:0019907)
defined
Definition | Parents |
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A cyclin-dependent kinase activating kinase complex capable of activating cyclin-dependent kinases by threonine phosphorylation, thus regulating cell cycle progression. consists of a kinase, cyclin and optional assembly factors, in human CDK7, CCNH and MNAT1. CAK activity is itself regulated throughout the cell cycle by T-loop phosphorylation of its kinase component (CDK7 in human). Phosphorylation of serine residues during mitosis inactivates the enzyme. Also capable of CAK phosphorylating the carboxyl-terminal domain (CTD) of RNA polymerase II and other transcription activating proteins, as part of the general transcription factor TFIIH. [PMID:8752210]
means. this is the kinas and the cyclin, so I would call it a
cyclin-dependent protein kinase ~activating~ kinase holoenzyme complex because it's the kinase and the cyclin, not something upstream.
The term is mislabeled and mis defined. It only has 11 EXP annotations.
I suggest obsoletion and just using the actual complex label (in my case [GO:0005675 transcription factor TFIIH holo complex)
I am not sure these are the same - see wikipedia: https://en.wikipedia.org/wiki/CDK-activating_kinase
Fission yeasts have two CAKs with both overlapping and specialized functions. The first CAK is a complex of Msc6 and Msc2. The Msc6 and Msc2 complex is related to the vertebrate Cdk7-cyclinH complex. Msc6 and Msc2 complex not only activates cell cycle Cdks but also regulates gene expression because it is part of the transcription factor TFIIH. The second fission yeast CAK, Csk1, is an ortholog of budding yeast Cak1. Csk1 can activate Cdks but is not essential for Cdk activity.[2]
So, if they are two complexes, they would be different and should not be children of each other.
Yes there are 2 CDK activiating kinases in pombe Cak1 and Msc6. I was confused because the name of this complex term is from the fact that the substrate is a 'cyclin dependent protein kinase', but Msc6 is itself a cyclin-dependent protein kinase (Cak1 isn't cyclin dependent)
I think the term was meant to cover the Msc6 (AKA Cdk7-cyclinH complex) which is equivalent to TFIIH, but not the the Cak1. Cak1 does not appear to be in a complex (there is no information about this for pombe or S. cerevisiae) . This term can only really apply to the TFIIH halo, and the final part of the def "Also capable of CAK phosphorylating the carboxyl-terminal domain (CTD) of RNA polymerase II and other transcription activating proteins, as part of the general transcription factor TFIIH. [PMID:8752210]" supports this.
I suggest we obsolete it because it is unnecessary, and confusing whatever it refers to. if it was supposed to include Cak1 it would be a strange grouping term (the common factor being the target protein, but there are other non-shared substrates)
This would be obsolete with consider GO:0005675 transcription factor TFIIH holo complex
I checked the existing 11 annotations https://www.ebi.ac.uk/QuickGO/annotations?goUsage=descendants&goUsageRelationships=is_a,part_of,occurs_in&goId=GO:0019907&evidenceCode=ECO:0000269&evidenceCodeUsage=descendants and all are GO:0005675 transcription factor TFIIH holo complex so this could be a direct replacement
GO:0005675 transcription factor TFIIH holo complex
GO:0019907 cyclin-dependent protein kinase activating kinase holoenzyme complex
(After discussion obsoletion was proposed as this is equivalent to TFIIH)