ISC1 (YER019W) notes

UniProt P40015, inositol phosphosphingolipid phospholipase C (IPS-PLC), neutral sphingomyelinase family; Mg2+-dependent [UniProt:P40015].

• Identified as IPS-PLC: PMID:11006294; deletion abolishes activity PMID:11006294. Hydrolyses IPC, MIPC and M(IP)2C to ceramide; also SM in vitro (not physiological in yeast, which lacks SM) [UniProt:P40015].
• Localization: ER early in growth, mitochondria (outer membrane) in late log/post-diauxic phase PMID:14699160; integral OMM protein PMID:17880915.
• Generates mitochondrial alpha-hydroxylated phytoceramides PMID:17880915.
• HU resistance via C18:1-phytoceramide / Cdc55-PP2A PMID:23620586; spindle checkpoint role PMID:32205408. These are downstream signalling roles of its ceramide product.

Pathway context

• YeastPathways places Isc1 on "phosphatidylcholine + H2O -> DAG + phosphocholine" (EC 3.1.4.3, PC-PLC) in phospholipid degradation (LIPASYN-PWY-1). No evidence Isc1 hydrolyses PC; its substrates are inositol phosphosphingolipids (and SM in vitro). The PC-PLC assignment is a YeastCyc error; RCA rows derived from it (PC-PLC activity, cytosol) are rejected.