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PomBase curation
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orthlogs, sphingo/ lipid metabolism #3244

Closed ValWood closed 3 months ago

ValWood commented 2 years ago

@dexink

ValWood commented 2 years ago

still need to look for

dexink commented 2 years ago

Not to mention the rest of the pathway that we hadn't gotten to yet by the end of yesterday

ValWood commented 2 years ago

There are not so many missing orthologs https://github.com/pombase/curation/issues/3245 The main question is whether all of the annotations are correct.

ValWood commented 2 years ago

Also to look for:

dexink commented 2 years ago

RE: YPC1/YDC1, definition UniProt lists two in their database with a precursory search, one per each name (YPC1 and YDC1)

ValWood commented 2 years ago

In my old losses file. These are proteins which are relatively highly conserved and would be unlikely to be very divergent and difficult to detect.

YPC1 YBR183W paralog YDC1 (conserved in human ACER3) (no compara) ceramide YDC1 YPL087W paralog YPC1 (conserved in human ACER3) (no compara) ceramide DPL1 YDR294C (from Compara) sphingolipid

So I agree these are gene loss in fission yeast YPC1 /YDC1

dexink commented 2 years ago

RE: CSG2, definition Purportedly part of a heterodimer via UniProt with either CSH1 or SUR1 Interesting, this is not corroborated by the listed binary interactions on the same entry page

KEGG orthologs is negative for S. pombe UniProt page reads the following for the function in S. cerevisiae, which links ceramide biosynthesis to inositol derivatives: "Required for calcium regulation. May regulate calcium accumulation by a non-vacuole organelle. Also regulates the activity of CSH1 and SUR1 during mannosyl phosphorylinositol ceramide synthesis."

Inositol metabolic pathways may need better resolving; potential for replacement of other central metabolism that is missing in S. pombe (?)

Still looking for homolog of CSG2 in S. pombe

dexink commented 2 years ago

Possibly interesting: STRING network for SPCC1450.15.1 (pig-F/3-ketosphinganine reductase fusion protein) links ceramide biosynthesis to tryptophan biosynthesis, mTor, the erf2-erf4 complex, and a chaperonin-containing t-complex: Network (no textmining, no co-expression; 2nd shell = no more than 30 interactors)

Nodes that may be of particular interest are SPCC320.14 (a racemase) and SPBC119.09c, a purported member of the SPOTS complex for which Pombase has its characterization status listed as "biological role inferred". Even more interesting, the latter node, as shown in the network, is linked directly to SPAC23A1.05, the protein that we determined had somehow been misannotated at some point as "lcb3"(!). (Recall that we were able to determine that the true S. cerevisiae Lcb3 ortholog in S. pombe was actually SPAC823.11 (currently annotated as "sgp1" in Pombase); it is also in the network and is clustered, as would be expected, with the other nodes linked to ceramide biosynthesis)

Do we think that SPAC23A1.05 was misannotated as Lcb3 because of an observed link to the other proteins we've confirmed as being involved in ceramide biosynthesis, and so in the past had been mistaken for one of the remaining players missing from the S. pombe pathway compared to that in S. cerevisiae?

Ultimately, it's possible that we may want to add a D-tryptophan (or D-amino acid) pathway to the list of possible alternative routes of tryptophan degradation in S. pombe. Thoughts?

dexink commented 2 years ago

To add to the interest in the misannotated "lcb3" protein, Sgp1 (SPAC823.11), it appears to be a regulatory target of Sre1, a regulator of sterol biosynthesis (relates to issues #1324 & #3244 ) image

Other interesting targets of Sre1 (under hypoxic conditions) include:

dexink commented 2 years ago

RE: D-Tryptophan and Tryptophan degradation Another reaction is listed for this molecule in MetaCyc that I did not notice before; there are promiscuous amino acid-utilizing reactions that feed into ceramide/Sphingolipid metabolism pathways: image

ValWood commented 2 years ago

SPBC119.09c, SPAC23A1.05 and SPAC823.11 should be updated tomorrow. I will check. I had already done it but not committed.

ValWood commented 2 years ago

Do we think that SPAC23A1.05 was misannotated as Lcb3 because of an observed link to the other proteins we've confirmed as being involved in ceramide biosynthesis, and so in the past had been mistaken for one of the remaining players missing from the S. pombe pathway compared to that in S. cerevisiae?

It might be related to this link in some way, but I think it was an actual mistake because SPAC23A1.05 and the real LCB3 are nothing like each other in length (I would always want to see some support b before adding an ortholog predicting).

ValWood commented 2 years ago

Ultimately, it's possible that we may want to add a D-tryptophan (or D-amino acid) pathway to the list of possible alternative routes of tryptophan degradation in S. pombe.

yes if this looks like the route. We can begin to model this in Noctua training session.

ValWood commented 3 months ago

CLosing this one as all should be addressed went he pathways are built