Ipt1 (inositolphosphotransferase 1) is the mannosyl-diinositol phosphorylceramide (M(IP)2C) synthase of Saccharomyces cerevisiae, a multipass Golgi membrane protein of the Aur1 family. It transfers a second phosphoinositol group from phosphatidylinositol onto mannosylinositol phosphorylceramide (MIPC), releasing diacylglycerol and producing M(IP)2C, the terminal and most abundant complex sphingolipid of yeast membranes (EC 2.7.1.228). ipt1 deletion mutants lack M(IP)2C and accumulate MIPC but grow nearly normally; they are resistant to M(IP)2C-targeting antifungal plant defensins such as DmAMP1, slightly resistant to high Ca2+, and (together with skn1) show increased autophagy under nitrogen starvation. Because M(IP)2C is needed for the action of several membrane-acting toxins, ipt1 mutants are also resistant to the bacterial lipodepsipeptide syringomycin E and to Kluyveromyces lactis zymocin, whose toxic gamma subunit they fail to import.
Definition: Catalysis of the reaction: a mannosylinositol-1-phospho-N-acylsphingoid base (MIPC) + a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) = an inositol phosphomannosylinositol-1-phospho-N-acylsphingoid base (M(IP)2C) + a 1,2-diacyl-sn-glycerol.
Justification: EC 2.7.1.228 / RHEA:64540 and RHEA:55604 describe the terminal step of yeast complex sphingolipid synthesis, experimentally attributed to Ipt1, but GO has no corresponding MF; current annotations fall back to the generic GO:0016772. A sibling of GO:0045140 inositol phosphoceramide synthase activity would capture it.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000139 Golgi membrane | EXP PMID:14583628 Protein sorting in the late Golgi of Saccharomyces cerevisia... | ACCEPT | Summary: EXP for Golgi membrane from Lisman et al. 2004 (abstract-only cache describes Csg1/Csh1 co-localising with IPC synthase in the medial Golgi; the curator presumably saw Ipt1 data in the full text). Consistent with the Golgi location of the sphingolipid head-group transferases. Supporting Evidence: PMID:14583628 Addition of an extra phosphoinositol group onto MIPC generates mannosyldi-IPC (M(IP)2C), the final and most abundant sphingolipid in yeast. |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0134 Golgi membrane). Correct. Supporting Evidence: file:yeast/IPT1/IPT1-uniprot.txt Golgi apparatus membrane |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA placing the M(IP)2C synthase reaction in the cytosol (pathway default). Ipt1 is a multipass Golgi membrane protein. Reason: Pathway-default compartment contradicted by membrane localisation. Supporting Evidence: file:yeast/IPT1/IPT1-uniprot.txt Golgi apparatus membrane |
| GO:0006676 mannosyl diphosphorylinositol ceramide metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN001263009) for M(IP)2C metabolic process; the experimental source is Ipt1 itself (SGD:S000002479). Correct for Ipt1. Supporting Evidence: PMID:9368028 is necessary for synthesis of mannose-(inositol-P)2-ceramide (M(IP)2C), the most abundant and complex sphingolipid in S. cerevisiae |
| GO:0006676 mannosyl diphosphorylinositol ceramide metabolic process | IDA PMID:9368028 Synthesis of mannose-(inositol-P)2-ceramide, the major sphin... | ACCEPT | Summary: IDA (Dickson et al. 1997) - ipt1 membranes cannot incorporate PI-derived inositol phosphate into M(IP)2C. Core process (M(IP)2C formation). Supporting Evidence: PMID:9368028 membranes prepared from it do not incorporate [3H-inositol]phosphatidylinositol into M(IP)2C, indicating a lack of M(IP)2C synthase activity |
| GO:0010507 negative regulation of autophagy | IGI PMID:20030721 Skn1 and Ipt1 negatively regulate autophagy in Saccharomyces... | KEEP AS NON CORE | Summary: IGI (Thevissen et al. 2010) with SKN1 (S000003375) - the ipt1 skn1 double mutant lacking M(IP)2C shows increased autophagy under nitrogen starvation. Indirect consequence of altered membrane sphingolipid composition. Reason: Downstream physiological effect of M(IP)2C deficiency. Supporting Evidence: PMID:20030721 Ξipt1 Ξskn1 mutant is characterized by increased autophagy under N starvation |
| GO:0016020 membrane | IDA PMID:6991492 Biosynthesis of phosphoinositol-containing sphingolipids fro... | ACCEPT | Summary: IDA (Becker & Lester 1980) - inositol phosphosphingolipid synthesis from PI by yeast membrane preparations, including an M(IP)2C-like product. Correct, general. Supporting Evidence: PMID:6991492 incubation of yeast membranes with [32P]phosphatidylinositol gave rise to a product that was chromatographically indistinguishable from the major yeast phosphosphingolipid |
| GO:0016020 membrane | ISM PMID:9368028 Synthesis of mannose-(inositol-P)2-ceramide, the major sphin... | ACCEPT | Summary: ISM (Dickson et al. 1997) - predicted multiple transmembrane segments of the Aur1-family protein. Correct. Supporting Evidence: PMID:9368028 Using the Aur1 protein sequence, recently identified as necessary for synthesis of the sphingolipid inositol-P-ceramide (IPC), we show that a homolog |
| GO:0016772 transferase activity, transferring phosphorus-containing groups | IDA PMID:9368028 Synthesis of mannose-(inositol-P)2-ceramide, the major sphin... | ACCEPT | Summary: IDA (Dickson et al. 1997) for transferase activity, transferring phosphorus-containing groups - M(IP)2C synthase (PI:MIPC phosphoinositol transferase) activity is absent from ipt1 membranes. Correct but generic; GO lacks a specific term for this reaction (EC 2.7.1.228), proposed as a new term. Supporting Evidence: PMID:9368028 indicating a lack of M(IP)2C synthase activity (putatively phosphatidylinositol:mannose-inositol-P-ceramide phosphoinositol transferase) |
| GO:0016772 transferase activity, transferring phosphorus-containing groups | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA for the M(IP)2C synthase step (EC 2.7.1.-). Correct but generic for want of a specific term. Supporting Evidence: PMID:9368028 indicating a lack of M(IP)2C synthase activity (putatively phosphatidylinositol:mannose-inositol-P-ceramide phosphoinositol transferase) |
| GO:0030148 sphingolipid biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN001263009) for sphingolipid biosynthetic process. Correct. Supporting Evidence: PMID:9368028 is necessary for synthesis of mannose-(inositol-P)2-ceramide (M(IP)2C), the most abundant and complex sphingolipid in S. cerevisiae |
| GO:0030148 sphingolipid biosynthetic process | IGI PMID:15792805 SKN1, a novel plant defensin-sensitivity gene in Saccharomyc... | ACCEPT | Summary: IGI (Thevissen et al. 2005) with SKN1 - IPT1 overexpression complements skn1 for M(IP)2C levels. Supporting Evidence: PMID:15792805 These results show that SKN1, together with IPT1, is involved in sphingolipid biosynthesis in S. cerevisiae. |
| GO:0030148 sphingolipid biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (yeast sphingolipid biosynthesis, terminal M(IP)2C step). Correct. Supporting Evidence: PMID:9368028 is necessary for synthesis of mannose-(inositol-P)2-ceramide (M(IP)2C), the most abundant and complex sphingolipid in S. cerevisiae |
| GO:0070916 inositol phosphoceramide synthase complex | IBA GO_REF:0000033 | REMOVE | Summary: PAINT IBA for inositol phosphoceramide synthase complex, whose only experimental source is Aur1 (SGD:S000001487), the IPC synthase that forms a complex with Kei1. Ipt1 is a paralog catalysing a different step (M(IP)2C synthesis); no study places Ipt1 in the Aur1-Kei1 complex or shows it needs Kei1. Reason: Complex membership of a paralog propagated to a different enzyme. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG COMPARTMENT OR COMPLEX MISMATCH Sources checked: SGD:S000001487 Β· AUR1 (IPC synthase catalytic subunit) SUPPORTS SOURCE BUT NOT TARGET Aur1-Kei1 complex is specific to the IPC synthase step; Ipt1 makes M(IP)2C. Supporting Evidence: PMID:9368028 M(IP)2C synthase activity is inhibited in the micromolar range by aureobasidin A, but drug sensitivity is over 1000-fold lower than reported for IPC synthase activity. |
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Download this section (compressed HTML)Q: GO:0045140 inositol phosphoceramide synthase activity is classified under hexosyltransferase activity, although IPC and M(IP)2C synthases transfer phosphoinositol from PI (phosphotransferases, EC 2.7.1.227/228). Should the term be re-parented, with a sibling term added for the M(IP)2C synthase reaction?
Inositolphosphotransferase; involved in synthesis of mannose-(inositol-P)2-ceramide (M(IP)2C), the most abundant sphingolipid; can mutate to resistance to the antifungals syringomycin E and DmAMP1 and to K. lactis zymocin
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