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geneontology / go-annotation

This repository hosts the tracker for issues pertaining to GO annotations.
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PTN000299690 #2034

Closed ValWood closed 5 years ago

ValWood commented 6 years ago

In higher eukaryotes this family is a likely endomembrane acetyl A transporter. I don't know if it is a proton symporter, but I don't think this can be transferred from E.coli. It seems unlikely

thomaspd commented 5 years ago

The alignment looks quite conserved even between eukaryotes and prokaryotes, and there are few duplication and divergence events. I think conservation of the proton symporter mechanism is a reasonable inference, and this mechanism is specifically listed in the TCDB description of the MFS superfamily: 2.A.1 The Major Facilitator Superfamily (MFS)

The MFS is a very old, large and diverse superfamily that includes millions of sequenced members. They catalyze uniport, solute:cation (H+, but seldom Na+) symport and/or solute:H+ or solute:solute antiport. Most are of 400-600 amino acyl residues in length and possess either 12, 14, or occasionally, 24 transmembrane α-helical spanners (TMSs). The mechanistic principles applicable to all MFS carriers have been summarized by Law et al (2008), while Zhang et al. 2015 considered the interaction between protonation and the negative-inside membrane potential. Functional roles of the conserved sequence motifs were also discussed in the context of the 3D structures.

ValWood commented 5 years ago

I think what I found odd here was the combination of "peptidoglycan" and "proton" transport. it seemed an unlikely combination. But I can't find the family member that alerted me to check why exactly I didn't like it!

ValWood commented 5 years ago

I could only find this http://www.pantree.org/tree/family.jsp?accession=PTHR12778

ValWood commented 5 years ago

But not all MFS transfer protons https://www.pombase.org/gene_subset/interpro:IPR036259 although some are substrate/proton symporters

ValWood commented 5 years ago

Only some of these function as co-transporters..

thomaspd commented 5 years ago

The PANTHER family is a very restricted family within the massive MFS superfamily, so we expect a range of mechanisms between families, but not likely within them.

For pombe, the family member is SPBC21B10.09 To see the MOD family members, as well as the alignment: http://www.pantherdb.org/treeViewer/treeViewer.jsp?book=PTHR12778&seq=HUMAN|HGNC=95|UniProtKB=O00400&species=agr (you can click on the gene ID column to bring up a web page in your browser with more information

ValWood commented 5 years ago

OK so is this one acetyl CoA/proton? In that case seems fine.

thomaspd commented 5 years ago

Right now, the substrate/solute isn't specified, so it's just the more general solute/proton term. In a quick check, I don't see any experimental annotations showing acetyl coA as the substrate, so we can't annotate that at this point. I will close this issue.