Aur1 is the catalytic subunit of inositol phosphorylceramide (IPC) synthase in Saccharomyces cerevisiae, an essential multipass membrane enzyme of the medial Golgi that transfers the phosphoinositol head group from phosphatidylinositol to ceramide (mainly alpha-hydroxylated very-long-chain phytoceramide), producing IPC and diacylglycerol (EC 2.7.1.227). This is the first committed step in the synthesis of complex sphingolipids, and the active site faces the Golgi lumen. Aur1 functions in a complex with the essential regulatory subunit Kei1, which is needed for its activity and Golgi retention. Aur1 is the target of the antifungal cyclic peptide aureobasidin A (and of khafrefungin and rustmicin); loss of activity causes ceramide accumulation and cell death.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:19726565 Kei1: a novel subunit of inositolphosphorylceramide synthase... | REMOVE | Summary: IPI (Sato et al. 2009) - Aur1 co-immunoprecipitates with Kei1 (Q06346), the regulatory subunit of IPC synthase. Real and functionally important, but better captured by complex membership (GO:0070916). Reason: Uninformative 'protein binding' (removal does not mean the interaction is false); the Aur1-Kei1 association is represented by the IPC synthase complex annotation GO:0070916. Supporting Evidence: PMID:19726565 Aur1 and Kei1 proteins form a complex in vivo |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: IPI from a proteome-wide interactome study (Michaelis et al. 2023) recovering the Aur1-Kei1 pair. Corroborates the complex but adds no functional information beyond GO:0070916. Reason: Uninformative 'protein binding' (the interaction itself is real); captured by IPC synthase complex membership GO:0070916. Supporting Evidence: PMID:19726565 Aur1 and Kei1 proteins form a complex in vivo |
| GO:0005783 endoplasmic reticulum | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | KEEP AS NON CORE | Summary: HDA from the SWAT-GFP library. Aur1 transits the ER as a newly made multipass protein, but its steady-state and functional site is the Golgi; ER signal in a tagging screen may reflect biosynthetic transit or tag effects. Reason: High-throughput observation not matching the targeted Golgi localisation. Supporting Evidence: PMID:10888667 was found to be located in the Golgi apparatus by both immunofluorescence and membrane fractionation, with its active site apparently in the Golgi lumen |
| GO:0005794 Golgi apparatus | IDA PMID:10888667 Inositol phosphorylceramide synthase is located in the Golgi... | ACCEPT | Summary: IDA (Levine et al. 2000) - immunofluorescence and membrane fractionation place Aur1 in the Golgi with a lumenal active site; the site of IPC synthesis. Supporting Evidence: PMID:10888667 was found to be located in the Golgi apparatus by both immunofluorescence and membrane fractionation, with its active site apparently in the Golgi lumen |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA placing the IPC synthase reaction of SPHINGOLIPID-SYN-PWY-1 in the cytosol (pathway default). Aur1 is a multipass Golgi membrane enzyme with its active site in the Golgi lumen. Reason: Contradicted by direct localisation and topology data. Supporting Evidence: PMID:10888667 with its active site apparently in the Golgi lumen |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000117 | TOO GENERAL | Summary: ARBA IEA for lipid metabolic process; correct but very general for a sphingolipid biosynthetic enzyme. Supporting Evidence: PMID:9092515 A gene, AUR1 (YKL004w), that complements the IPC synthase defect and restores enzyme activity and sphingolipid synthesis was isolated. |
| GO:0006673 inositol phosphoceramide metabolic process | IDA PMID:19726565 Kei1: a novel subunit of inositolphosphorylceramide synthase... | ACCEPT | Summary: IDA (Sato et al. 2009) - IPC synthase activity of Aur1-Kei1 membranes; IPC metabolism is the process Aur1 directly drives (IPC formation). Supporting Evidence: PMID:19726565 Aur1 without Kei1 has hardly detectable IPC synthase activity |
| GO:0006676 mannosyl diphosphorylinositol ceramide metabolic process | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: PAINT IBA (PTN001263009) for mannosyl diphosphorylinositol ceramide metabolic process. The node groups the IPC synthase Aur1 with its paralog Ipt1 (SGD:S000002479), the M(IP)2C synthase, and the experimental with/from is Ipt1. Aur1 makes IPC, the precursor two steps upstream; it does not make or metabolise M(IP)2C. Reason: Paralog-specific process (Ipt1) propagated to Aur1; Aur1 only supplies the upstream precursor IPC. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG Sources checked: SGD:S000002479 · IPT1 (M(IP)2C synthase) SUPPORTS SOURCE BUT NOT TARGET Ipt1 adds the second inositol phosphate to MIPC; Aur1 performs the first inositol phosphate transfer to ceramide. Supporting Evidence: PMID:9092515 the step in sphingolipid synthesis in which inositol phosphate is added to ceramide to form inositol-P-ceramide |
| GO:0030148 sphingolipid biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN001263009) for sphingolipid biosynthetic process, seeded by Aur1, Ipt1 and an Aspergillus homolog. Correct for Aur1. Supporting Evidence: PMID:9092515 A gene, AUR1 (YKL004w), that complements the IPC synthase defect and restores enzyme activity and sphingolipid synthesis was isolated. |
| GO:0030148 sphingolipid biosynthetic process | IMP PMID:9092515 Sphingolipid synthesis as a target for antifungal drugs. Com... | ACCEPT | Summary: IMP (Nagiec et al. 1997) - aur1 mutant fails to incorporate inositol or N-acetylsphinganine into sphingolipids and accumulates ceramide. Supporting Evidence: PMID:9092515 An IPC synthase defect is supported by data showing a failure of the mutant strain to incorporate radioactive inositol or N-acetylsphinganine into sphingolipids |
| GO:0030148 sphingolipid biosynthetic process | IPI PMID:19726565 Kei1: a novel subunit of inositolphosphorylceramide synthase... | ACCEPT | Summary: IPI (Sato et al. 2009) - Aur1 acts with Kei1 in IPC synthesis. Correct process. Supporting Evidence: PMID:19726565 Kei1 is essential for both the activity and the Golgi localization of IPC synthase |
| GO:0030148 sphingolipid biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (yeast sphingolipid biosynthesis, IPC synthase step). Correct. Supporting Evidence: PMID:9092515 the step in sphingolipid synthesis in which inositol phosphate is added to ceramide to form inositol-P-ceramide |
| GO:0032580 Golgi cisterna membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (Golgi stack membrane), based on Levine et al. 2000 and Sato et al. 2009 (medial Golgi). Correct. Supporting Evidence: file:yeast/AUR1/AUR1-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane |
| GO:0045140 inositol phosphoceramide synthase activity | IDA PMID:19047657 Inhibition of inositol phosphorylceramide synthase by the cy... | ACCEPT | Summary: IDA (Aeed et al. 2009) - kinetic analysis of IPC synthase in washed membranes with PI and ceramide substrates, and of an AbA-resistant Aur1 mutant enzyme. Core activity. Supporting Evidence: PMID:19047657 The K(m) values for both substrates (ceramide and PI) were similar when they interacted with the mutant and the wild-type enzymes. |
| GO:0045140 inositol phosphoceramide synthase activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC-mapping IEA (EC 2.7.1.227). Correct. Supporting Evidence: file:yeast/AUR1/AUR1-uniprot.txt ChEBI:CHEBI:155886, ChEBI:CHEBI:155926; EC=2.7.1.227; |
| GO:0045140 inositol phosphoceramide synthase activity | IMP PMID:9092515 Sphingolipid synthesis as a target for antifungal drugs. Com... | ACCEPT | Summary: IMP (Nagiec et al. 1997) - the mutant lacks IPC synthase activity and AUR1 restores it; aureobasidin A inhibits the enzyme. Supporting Evidence: PMID:9092515 A gene, AUR1 (YKL004w), that complements the IPC synthase defect and restores enzyme activity and sphingolipid synthesis was isolated. |
| GO:0045140 inositol phosphoceramide synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (phytoceramide + PI -> IPC + DAG). Correct. Supporting Evidence: PMID:9092515 the step in sphingolipid synthesis in which inositol phosphate is added to ceramide to form inositol-P-ceramide |
| GO:0070916 inositol phosphoceramide synthase complex | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for IPC synthase complex; the node's experimental source is Aur1 itself (SGD:S000001487), whose complex with Kei1 is established. Correct. Supporting Evidence: PMID:19726565 Aur1 and Kei1 proteins form a complex in vivo |
| GO:0070916 inositol phosphoceramide synthase complex | IPI PMID:19726565 Kei1: a novel subunit of inositolphosphorylceramide synthase... | ACCEPT | Summary: IPI (Sato et al. 2009) - Aur1 forms a complex with Kei1 in vivo. Supporting Evidence: PMID:19726565 Aur1 and Kei1 proteins form a complex in vivo |
| GO:0070916 inositol phosphoceramide synthase complex | IPI PMID:19726565 Kei1: a novel subunit of inositolphosphorylceramide synthase... | ACCEPT | Summary: IPI (Sato et al. 2009) with KEI1 (SGD:S000002775) - same Aur1-Kei1 IPC synthase complex. Supporting Evidence: PMID:19726565 Aur1 and Kei1 proteins form a complex in vivo |
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Download this section (compressed HTML)Phosphatidylinositol:ceramide phosphoinositol transferase; required for sphingolipid synthesis; can mutate to confer aureobasidin A resistance; also known as IPC synthase
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