Sur2 (Syr2; YDR297W) is the sphingolipid C4-hydroxylase of Saccharomyces cerevisiae, an integral endoplasmic reticulum membrane enzyme of the sterol desaturase/fatty acid hydroxylase family that uses a histidine-box diiron centre, O2 and electrons from cytochrome b5. It hydroxylates C-4 of the sphingoid base, converting sphinganine (dihydrosphingosine) and dihydroceramides to phytosphingosine and phytoceramides (EC 1.14.18.5), which provides the 4-hydroxylated long-chain base characteristic of yeast sphingolipids. sur2 null mutants are viable and make normal amounts of sphingolipids built on dihydrosphingosine instead of phytosphingosine. The 4-hydroxyl group is required for growth inhibition by the Pseudomonas syringae lipodepsipeptide syringomycin E, which is how SYR2 was first identified.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005506 iron ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro (IPR050307, sterol desaturase-related) IEA for iron ion binding. Sur2 is a His-box diiron oxygenase, so iron binding is a correct cofactor-level statement, but it is subsidiary to the C4-monooxygenase activity. Supporting Evidence: PMID:9556590 the predicted Syr2p shows sequence similarity to diiron-binding membrane enzymes involved in oxygen-dependent modifications of hydrocarbon substrates |
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PTN000933267) for ER membrane, consistent with the direct ER localization of Syr2p. Supporting Evidence: PMID:8868422 shown to encode a 349 amino acid protein located in the endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:8868422 SYR2, a gene necessary for syringomycin growth inhibition of... | ACCEPT | Summary: IDA from Cliften et al. 1996, which showed Syr2p is located in the endoplasmic reticulum. Supporting Evidence: PMID:8868422 shown to encode a 349 amino acid protein located in the endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping (SL-0097) IEA; UniProt bases ER membrane on Cliften et al. 1996. Correct. Supporting Evidence: file:yeast/SUR2/SUR2-uniprot.txt -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005829 cytosol | RCA GO_REF:0000123 | MODIFY | Summary: YeastPathways RCA (SPHINGOLIPID-SYN-PWY-1) default cytosol placement for the C4-hydroxylase step. Sur2 is an integral ER membrane protein, so cytosol (which excludes membranes) is the wrong compartment. Reason: Pathway default compartment conflicts with experimental ER localization. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:8868422 shown to encode a 349 amino acid protein located in the endoplasmic reticulum |
| GO:0006665 sphingolipid metabolic process | IMP PMID:9556590 Syringomycin action gene SYR2 is essential for sphingolipid ... | TOO GENERAL | Summary: IMP from Grilley et al. 1998: syr2 disruptants make sphingoid bases lacking the 4-hydroxyl group. Correct, if broad; the biosynthetic and C4-monooxygenase annotations are more specific. Supporting Evidence: PMID:9556590 yeast strains carrying a disrupted SYR2 allele produced sphingoid long chain bases lacking the 4-hydroxyl group present in wild type strains |
| GO:0008610 lipid biosynthetic process | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro (IPR050307) IEA for lipid biosynthetic process. True but very general; sphingolipid biosynthetic process / sphingoid biosynthetic process capture the role. Supporting Evidence: PMID:9556590 These results show that the SYR2 gene is required for the 4-hydroxylation reaction of sphingolipid long chain bases |
| GO:0030148 sphingolipid biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway (UPA00786) IEA. Sur2 makes phytosphingosine/phytoceramide in de novo sphingolipid synthesis. Supporting Evidence: PMID:9556590 These results show that the SYR2 gene is required for the 4-hydroxylation reaction of sphingolipid long chain bases |
| GO:0030148 sphingolipid biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (SPHINGOLIPID-SYN-PWY-1) placing the sphinganine C4-hydroxylation step in sphingolipid biosynthesis; correct for Sur2. Supporting Evidence: PMID:9556590 These results show that the SYR2 gene is required for the 4-hydroxylation reaction of sphingolipid long chain bases |
| GO:0042284 sphingolipid delta-4 desaturase activity | IBA GO_REF:0000033 | REMOVE | Summary: IBA (PTN000933245, seeded from S. pombe SPBC887.15c) for sphingolipid delta-4 desaturase activity, i.e. formation of sphing-4-enine (sphingosine-type) ceramides. Sur2 is a C4 hydroxylase, not a desaturase: S. cerevisiae sphingolipids carry 4-hydroxylated (phyto) or saturated (dihydro) bases, and sur2 mutants simply lack the 4-hydroxyl group. Delta-4 desaturation is done by the unrelated DEGS/Des1 family, which S. cerevisiae lacks. Reason: The desaturase reaction is not carried out by Sur2; the propagated activity conflicts with the experimentally defined C4-hydroxylase chemistry of this protein. Propagation Review Root cause: UNRESOLVED Failure modes: ROLE CONFLATION Sources checked: PomBase:SPBC887.15c · S. pombe Sur2 ortholog UNRESOLVED Donor annotation not inspected here. Sur2-family enzymes are C4-hydroxylases; delta-4 desaturation belongs to the unrelated DEGS family, absent from S. cerevisiae. Supporting Evidence: PMID:9556590 yeast strains carrying a disrupted SYR2 allele produced sphingoid long chain bases lacking the 4-hydroxyl group present in wild type strains PMID:9556590 These results show that the SYR2 gene is required for the 4-hydroxylation reaction of sphingolipid long chain bases |
| GO:0046520 sphingoid biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PTN000933267, with Arabidopsis SBH1/SBH2 donors) for sphingoid biosynthetic process. Sur2 produces the 4-hydroxylated sphingoid base phytosphingosine. Supporting Evidence: PMID:9556590 These results show that the SYR2 gene is required for the 4-hydroxylation reaction of sphingolipid long chain bases |
| GO:0102772 sphingolipid C4-monooxygenase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PTN000933267) for sphingolipid C4-monooxygenase activity; Sur2 is itself among the experimentally grounded members, which is expected. Supporting Evidence: PMID:9556590 4-hydroxylase activity was increased in microsomes prepared from a SYR2 overexpression strain |
| GO:0102772 sphingolipid C4-monooxygenase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Rhea-based IEA (RHEA:46364, RHEA:55476: N-acylsphinganine C4-hydroxylation). Matches UniProt's experimentally supported reactions for Sur2. Supporting Evidence: file:yeast/SUR2/SUR2-uniprot.txt Reaction=an N-acylsphinganine + 2 Fe(II)-[cytochrome b5] + O2 + 2 H(+) |
| GO:0102772 sphingolipid C4-monooxygenase activity | IMP PMID:9556590 Syringomycin action gene SYR2 is essential for sphingolipid ... | ACCEPT | Summary: IMP from Grilley et al. 1998: loss of 4-hydroxylated bases in syr2 cells and increased microsomal 4-hydroxylase activity on overexpression. Core activity. Supporting Evidence: PMID:9556590 yeast strains carrying a disrupted SYR2 allele produced sphingoid long chain bases lacking the 4-hydroxyl group present in wild type strains PMID:9556590 4-hydroxylase activity was increased in microsomes prepared from a SYR2 overexpression strain |
| GO:0102772 sphingolipid C4-monooxygenase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA for the sphinganine -> phytosphingosine step (EC 1.14.18.5). Correct; Sur2 also hydroxylates dihydroceramide, which the GO term definition covers. Supporting Evidence: file:yeast/SUR2/SUR2-uniprot.txt Reaction=sphinganine + 2 Fe(II)-[cytochrome b5] + O2 + 2 H(+) = (4R)- |
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Experiment: Assay purified Sur2 with cytochrome b5/b5 reductase on free sphinganine versus dihydroceramide to establish the in vivo order of C4-hydroxylation relative to N-acylation.
Sphinganine C4-hydroxylase; catalyses the conversion of sphinganine to phytosphingosine in sphingolipid biosyntheis
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