sphingolipid/ceramide metabolism pathway members for Noctua modelling

[ValWood]

@dexink

pombe orthologs of cerevisiae proteins annotated to sphingolipid metabolic process , & regulation of sphingolipid metabolic process for Noctua modelling

pombe	cerevisiae
SPCC1450.15: pig-F/3-ketosphinganine reductase fusion protein	TSC10
Sur2: sphingosine hydroxylase/sphingolipid delta-4 desaturase	SUR2
Pkd2: plasma membrane TRP-like calcium ion channel Pkd2 (some weirdness here)	FLC1, FLC2, FLC3, YOR365C???
Imt1,2,3 (some weirdness here)	SUR1, CSH1
Seems to be absent, take a closer look?	YPC1, YDC1
Ifa38: ketoreductase involved in fatty acid elongation	IFA38
?	CSG2
Lcb4: sphingoid long chain base kinase	LCB5
Arv1: sphingoid long chain base kinase Arv1	ARV1
Spg1: sphingosine-1-phosphate phosphatase Spg1	YSR3 , LCB3
Phs1: 3-hydroxyacyl-CoA dehydratase involved in very long-chain fatty acid elongation Phs1	PHS1
???	LIP1
Lcb1: serine palmitoyltransferase complex subunit	LCB1
Lag1 & Lac1 sphingosine N-acyltransferase	LAG1, LAC1
Aur1: inositol phosphorylceramide synthase	IPT1
Lcb2: serine palmitoyltransferase	LCB2
Lcb4: sphingoid long chain base kinase	LCB4
Aur1: Inositol phosphorylceramide synthase	AUR1 , IPT1
Ste20 Rictor homolog, Ste20 (UPSTREAM SIGNALLING)	TSC11
Css1: inositol phosphosphingolipid phospholipase C, Css1	ISC1
Sbg1: plasma membrane-actinomyosin ring linker protein	SKN1 (looks indirect), KRE6
Elo1: fatty acid elongase	ELO1, ELO3 (Add ELO2 as another paralog?)
sei1	SEI1
orm1	ORM1, ORM2
SPAC23A1.05	TSC3
sck1	SCH9
???	LDB16
oca2	NPR1
gad8	YPK1
tor2	TOR1
wee1	SWE1

additional pombe proteins annotated to sphingolipid metabolic process mel1 dsd1 mpo1 scs7 pvg2 kei1 pdf1 SPCC1450.15 ~lcb3~ now ? SPAPB1A10.07c SPAC17G6.11c

S. cerevisiae SAc1 Is annotated to SPOTS complex (but doesn't not have sphingosine metabolism annotation)

[dexink]

@ValWood I suppose in order to annotate either as participating in the SPOTS complex, such a complex would need to be confirmed in both yeasts? It is originally characterized in mammals, it seems like (?)

[dexink]

Also, I don't see Sre1 in the above list, although I keep finding it across the proteins we reviewed so far in relation to ceramide/sphingolipid biosynthesis as a positive regulator

[dexink]

Additionally (for model; need to check onboarding progress) I have some suspicions that the pig-F/3-ketosphinganine reductase fusion protein (SPCC1450.15) may have two (possibly 3) functions in this pathway:

1) Ethanolamine phosphate is produced in two separate places downstream of the step completed by 3-ketosphinganine reductase, a non-membraneous domain: in both instances it is a product of Sphingosine-1-phosphate lyase (SPL) (**Edit: actually, ethanolamine phosphate is produced in more than two places, I missed the other one before)

2) GO annotation predicts an additional contribution as a phosphotransferase as a result of the fused pig-F domain, the S. cerevisiae ortholog acting to transfer phosphoethanolamine to the multiply-mannosylated glycosylphosphatidylinositol (GPI) intermediate

The gap in the pathway constituted by only these two enzymes, as proposed, bolsters the possibility that this fusion protein acts as part of a larger complex with SPL (and, further upstream, 3-ketosphinganine reductase) providing the necessary substrates for the activity of pig-F.

[ValWood]

I suppose in order to annotate either as participating in the SPOTS complex, such a complex would need to be confirmed in both yeasts? It is originally characterized in mammals, it seems like (?)

I will annotate to SPOTs, I can infer from experimental data in human (especially for complexes that are 1:1). However I have an outstanding GO question about the complex: https://github.com/geneontology/go-ontology/issues/23304 If the terms are merged as I expect (with SPOTs as the primary name), this will be resolved from the existing annotation.

https://www.pombase.org/term/GO:0017059

[ValWood]

Also, I don't see Sre1 in the above list, although I keep finding it across the proteins we reviewed so far in relation to ceramide/sphingolipid biosynthesis as a positive regulator

Sre1 is the transcription factor, so it's an upstream regulator. It is however bound to the ER membrane and then activated (Cleaved) by hypoxic conditions, but it is quite upstream from this part, but it can be included in the model.