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This repository hosts the tracker for issues pertaining to GO annotations.
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human PINC annotation to delete, not nucleocytoplamsic transport #1859

Closed ValWood closed 6 years ago

ValWood commented 6 years ago

I'm not looking into these, but they look incorrect

O60318 MCM3AP | Germinal-center associated nuclear protein |   | protein import into nucleus |   | PINC | Homo sapiens | TAS |   | 80 kda mcm3-associated protein pthr12436 |   | PMID:9712829

PDIA3 | Protein disulfide-isomerase A3 |   | protein import into nucleus |   | PINC | Homo sapiens | TAS |   | protein disulfide isomerase pthr18929 |   | PMID:7487104 | 20030904

ValWood commented 6 years ago

@pgaudet can you delete these?

pgaudet commented 6 years ago

MCM3AP The paper states that " Map80 may not participate in the import of MCM3 but stabilize the nuclear localization of MCM3 by interacting with other karyopheric materials, such as chromatin or other karyopheric protein"

-> I moved the annotation to 'regulation of protein localization to nucleus' - OK ? It definitely seem to have some role in nucleocytoplasmic transport: https://europepmc.org/articles/PMC3378895

pgaudet commented 6 years ago

PDIA3 Deleted

Thanks, Pascale  

pgaudet commented 6 years ago

@ValWood please next time include the AC or ID.

ValWood commented 6 years ago

Ah right MCM3AP is TREX, that does have a role in nucleocytoplasmic transport (it might be indirect but it is traditionally annotated to this term). However it isn't import, it's export.

re @ValWood please next time include the AC or ID. Will do- I cut and pasted the annotation from AmiGO, I thought the ID was in the annotation!

pgaudet commented 6 years ago

Did you look at the paper ? https://www.ncbi.nlm.nih.gov/pubmed/?term=9712829 MCM3AP seems to be required for the nuclear localization of a NLS-containing protein; could it have multiple roles ?

ValWood commented 6 years ago

I didn't but I will....I'm pretty certain this is nonsense. MCM3 has been getting into the nucleus pretty well without it in most other species ;)

Map80 May Be Involved in the Localization Pathway of MCM3 Xenopus MCM3 (XMCM3) was shown not to be imported into the nucleus, in contrast to hMCM3 (18). The amino acid sequences corresponding to the putative NLS region were compared. A cluster of basic amino acid residues, which is important for the function of the NLS (19), was identified in hMCM3 but not in XMCM3 (Fig.4 A). We prepared “mut. MCM3,” which is the same as hMCM3 except that 4 amino acids have been replaced with the corresponding amino acids of XMCM3 (Fig.4 A), and compared the cellular localization of these three MCM3 proteins, i.e. hMCM3, XMCM3, and mut. MCM3. As shown in Fig. 4 B, hMCM3 was localized in the nucleus, whereas XMCM3 was in the cytoplasm, and mut. MCM3 was in both the nucleus and the cytoplasm. The mutagenesis on putative NLS of hMCM3 affected the nuclear localization of hMCM3, indicating that the sequence was responsible for the localization of MCM3. Furthermore, as shown in Fig.4 C, the mutagenesis affected the interaction between Map80 and hMCM3 in a two-hybrid system. Map80 interacted with hMCM3 and weakly with mut. MCM3, but not with XMCM3. These results suggest that Map80 is necessary for the nuclear localization of hMCM3.

Nowhere here is there an assay for nucleocytolasmic transport. They delete the the NLS from MCM3 and it does not localize (not surprising) Mcm3 no longer interacts with map80 (OK MAp80 might bind this region) A fusion of human MLS- and map80 localizes to the nucleus (not surprising).

Later they say:

Map80 may not participate in the import of MCM3 but stabilize the nuclear localization of MCM3 by interacting with other karyopheric materials, such as chromatin or other karyopheric protein. It is tempting to speculate that Map80 has some function in the nucleus, because a fusion protein of Map80 and DNA binding domain of GAL4 activated the reporter gene transcription in yeast (data not shown).

ValWood commented 6 years ago

DNA binding from this paper probably needs deleting too?

ValWood commented 6 years ago

A more recent paper (not used for GO) https://www.ncbi.nlm.nih.gov/pubmed/22307388

pgaudet commented 6 years ago

Nucleic acid binding comes from InterPro @asangrador

Thanks, Pascale

asangrador commented 6 years ago

Are you referring to a match to IPR035979? This entry is annotated to nucleic acid binding, but I don't think it is wrong. It represents a RRM domain in the multidomain protein GANP, not present in the shorter isoform GANP/MCM3AP or in pombe SAC3. And GANP associates with cromatin according to PMID:23652018.

ValWood commented 6 years ago

  1. The DNA binding is from Prot inc (TAS), that should go. At least from this paper.

  2. It most likely does bind RNA (TREX associates with RNA polymerase, and RNAs).

  3. The proposed "acetyl transferase domain" appears to be not functionally relevant. Lots of authors refer to it, but I can't see anything which confirms this activity, and the original authors see also this ticket. https://github.com/geneontology/go-annotation/issues/1861

Later the authors say in another paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037533/ more recent work from the same lab downplays the acetyase activity inthe MCM3AP fragment Furthermore, because GANP also contains a region identical to MCM3AP (MCM3 acetylating protein), that interacts with and weakly acetylates MCM3,31,32 these proteins have often been confused in databases and the literature.

The original alignment with GNAT looks spurious

ValWood commented 6 years ago

related https://github.com/geneontology/go-annotation/issues/1861

pgaudet commented 6 years ago

Hi @ValWood I deleted the DNA binding annotation.

Thanks,Pascale

pgaudet commented 6 years ago

and the nuclear import.