PANTHER:PTN001052033

[ValWood]

http://amigo.geneontology.org/amigo/gene_product/PomBase:SPCC162.08c http://www.pantree.org/node/annotationNode.jsp?id=PTN001052033

is annotated to mitotic spindle assembly checkpoint

it comes from these 2 annotations human P12270 fly A1Z8P9 but there is no such evidence in yeast where the process is studied in more detail....

[thomaspd]

So should we have these primary annotations in human and fly reviewed? Or do you think we should just remove the PAINT annotation?

[ValWood]

I think it's OK for human https://www.uniprot.org/citations/18981471 It does affect cell cycle regulation. Howver, It is still unclear to me whether these should be annotated to the signalling pathway, because I'm not sure whether these are just phenotypes due to defects in translocation into the nucleus, or they have a more direct role in regulating the spindle checkpoint.

During the signalling workshop the decision was not to annotate in the MAPK pathway in a similar situation.

In the G2/M transition pathway the translocation into the nucleus is a rate-limiting step, but it isn't really regulatory in the sense that the nuclear pore protein isn't doing anything mechanistically (its just a slower step than the transfer of wee1 from the membrane to the nuclear boundary), but in a normal cell I don't see that this participates in the regulation (it isn't actually modulating it takes as long as it takes). I still wanted to talk to my cell cycle experts about this and I probably haven't articulated it very well.

Based on the current evidence this doesn't seem to be spindle checkpoint ( in yeast different nucleoporins give checkpoint phenotypes). Certainly the nuclear pore affects most cell cycle regulation/checkpoints strongly (many nucleoporins are absolutely essential for cell cycle progression).

In fission yeast we have shown that nup11 ablation results in cell cycle delay phenotype, https://www.pombase.org/reference/PMID:23697806 but we also showed this for >500 other gene products and we don't want to annotate these to cell cycle regulation based on this evidence (this is a good example for the causally upstream discussion).

v

[thomaspd]

OK, if I understand correctly, we'll wait for you to check with your cell cycle experts on this one. I'll assign this ticket to you for now.

[pgaudet]

@valwood any news ?

[ValWood]

No, I didn't fiollow up yet. Won't have time until after grant/ISB. v

[pgaudet]

@ValWood ping

[ValWood]

TPR P12270 is a nuclear pore scaffold.

This is probably OK. There is evidence that these have a role in the checkpoint localization. I have never really established whether this localization is causally upstream or part of the checkpoint pathway. I tend to think it's upstream since the tension sensor would probably be the beginning of the pathway. However I have seen nuclear pore proteins across all species annotated to this term, and the papers describe as being involved in recruitment:

https://www.ncbi.nlm.nih.gov/pubmed/19273613 putative spindle matrix has been hypothesized to mediate chromosome motion, but its existence and functionality remain controversial. In this report, we show that Megator (Mtor), the Drosophila melanogaster counterpart of the human nuclear pore complex protein translocated promoter region (Tpr), and the spindle assembly checkpoint (SAC) protein Mad2 form a conserved complex that localizes to a nuclear derived spindle matrix in living cells. Fluorescence recovery after photobleaching experiments supports that Mtor is retained around spindle microtubules, where it shows distinct dynamic properties. Mtor/Tpr promotes the recruitment of Mad2 and Mps1 but not Mad1 to unattached kinetochores (KTs), mediating normal mitotic duration and SAC response. At anaphase, Mtor plays a role in spindle elongation, thereby affecting normal chromosome movement. We propose that Mtor/Tpr functions as a spatial regulator of the SAC, which ensures the efficient recruitment of Mad2 to unattached KTs at the onset of mitosis and proper spindle maturation, whereas enrichment of Mad2 in a spindle ma

The best action here is probably to keep the annotations, but not to transfer to yeast because it seems that we would annotate as causally upstream if the beginning and ends of checkpoint are established.

Also the requirements for keeping the localization in mitosis will be different for open and closed mitosis so the role may be more direct in higher eukaryotes with open mitosis.

[ValWood]

I would just transfer this conservatively among higher eukaryotes for now...

[pgaudet]

OK, fixed.