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Source ontology files for the Gene Ontology
http://geneontology.org/page/download-ontology
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Fix definition and parentage Ino80 complex (GO:0031011) #21776

Closed ValWood closed 3 years ago

ValWood commented 3 years ago

Definition | A multisubunit protein complex that contains the Ino80p ATPase; exhibits chromatin remodeling activity ~and 3' to 5' DNA helicase activity~.

reason: Ino80 is a ATP-dependent chromatin remodelled, but not a helicase.

also remove is_a DNA helicase complex (GO:0033202)

@colinlog @bmeldal @pgaudet

bmeldal commented 3 years ago

Acc to PMID:10952318, Fig 3, it has GO:0043138 3'-5' DNA helicase activity - at least in Saccharomyces cerevisiae.

ValWood commented 3 years ago

I think it probably has in vitro, but it isn't now considered to be a helicase. @colinlog is that correct?

colinlog commented 3 years ago

10952318 Nature 2000, shows (weak?) helicase activity for the complex, but they do not pin it down to one of the ATPases (INO80, Rvb1 or Revb2). So, Birgits helicase annotation is a fine representation of the biochemistry performed by the INO80 complex (although it is perhaps a dubious report / an artifactual helicase assay activity documentation), but, I would defintely not use this paper to annotate Rvb1/2 nor Ino80 ATPases as possessing [intrinsic/physiologically relevant] helicase activity.

From https://elifesciences.org/articles/63042 (PMID:33205750) it is clear that no helicase activity is detected for Rvb1/2. Rather, Ruvb1 and RuvB2 appear to be protein complex shakers/assembly chaperones. One quote from the intro is "RUVBL1 and RUVBL2 are essential constituents of several large complexes. In various chromatin-remodeling complexes such as INO80 and SRCAP, these ATPases form a scaffold that organizes the architecture of other subunits in the complex (Aramayo et al., 2018; Eustermann et al., 2018; Feng et al., 2018). RUVBL1 and RUVBL2 also interact with RPAP3 and PIH1D1 proteins to form the R2TP complex, a HSP90 co-chaperone involved in the assembly and maturation of some large complexes including RNA polymerase II and members of the Phosphatidylinositol 3-kinase-related kinase (PIKK) family such as ATR, ATM, SMG1, and mTOR (Houry et al., 2018; Martino et al., 2018; Maurizy et al., 2018; Muñoz-Hernández et al., 2019; Rivera-Calzada et al., 2017). ". Altogether, at this point in time I do not know of other papers than the 2000 Nature paper by Carl Wu that demonstrated helicase activity either for Ino80 SNF2-type DEAD/H ATPase or for the Rvb1/2 AAA+ ATPase rings.

A chaperone/protein complex (dis)assembly activity that I would colloquially term 'protein complex shaking' is very likely for the Rvb1/2 rings.

bmeldal commented 3 years ago

So, in a nutshell, although there's weak in vitro evidence that a INO80 complex might have helicase activity it's not generally accepted to have it in vivo.

If that's the case, I'd happily remove it from the complexes.

colinlog commented 3 years ago

That would be the careful conclusion, unless data to the contrary is found in the literature.

bmeldal commented 3 years ago

Ok, helicase annotations removed. Can always be added again if new evidence emerges.

colinlog commented 3 years ago

The paper to look at for Rvb1/2 (Tip49a/b) helicase activity (and hexameric ring formation!) is PMID:18234224. What puzzles me is that in that paper the 5' to 3' helicase activity is strongest whilst in the other papers (including the Nature paper from 2000 PMID:10952318 as well as in PMID:10428817 and PMID:10336418 it was 3' to 5' activity that was highlighted and 5' to 3' that was considered weak. For sure, in PMID:18234224 the 3' to 5' helicase activity is weaker, and neither the Tip49 a only nor the Tip49b only reactions show any helicase activity.

All in all, I am still unsure what helicase activity to annotate, but from this paper (PMID:18234224), the Rvb1/Rvb2 (aka Tip49a/b) complexes would be 5' to 3' helicases.

pgaudet commented 3 years ago

How about "A multisubunit protein complex that contains the Ino80p ATPase; exhibits chromatin remodeling activity and in some species there is evidence for DNA helicase activity." ?

and remove the DNA helicase parentage.

ValWood commented 3 years ago

I don't know so I have asked Rob DeBruin whose lab works on Ino80.

SGD description of Ino80 is ATPase and nucleosome spacing factor; subunit of complex containing actin and actin-related proteins that has chromatin remodeling activity and 3' to 5' DNA helicase activity in vitro; promotes nucleosome shifts in the 3 prime direction; has a role in modulating stress gene transcription

It seems that the in vivo role is clearly nucleosome sliding rather than DNA unwinding.

pgaudet commented 3 years ago

I am assigning you, let me know if you want a different edit.

ValWood commented 3 years ago

OK the person that I thought works on this complex does not. But none of the high profile newer papers even mention a helicase role....

e.g. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163841/

ValWood commented 3 years ago

The most recent pombe paper that really digs into the function in vivo also does not mention helicase.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597579/ The Ino80 complex mediates epigenetic centromere propagation via active removal of histone H3

We should go with the current consensus.