scs7 (SPAC19G12.08; UniProt O13846) encodes the ceramide very-long-chain fatty acid 2-hydroxylase (FA2H/Scs7 family), an ER-membrane dimetal hydroxylase that lacks the N-terminal cytochrome b5 domain of its orthologs and hydroxylates the amide-linked VLCFA of ceramide at C2. The hydroxylated ceramides feed IPC and MIPC, the main complex sphingolipids of fission yeast. It is in the ER in a genome-wide screen.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005783 endoplasmic reticulum | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: ORFeome screen: ER. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference. Reason: UniProt records ER membrane location from the S. pombe ORFeome screen (ECO:0000269|PubMed:16823372), which supports the PAINT ER placement. Supporting Evidence: file:SCHPO/scs7/scs7-uniprot.txt Endoplasmic reticulum membrane {ECO:0000269|PubMed:16823372} |
| GO:0005789 endoplasmic reticulum membrane | IC GO_REF:0000036 | ACCEPT | Summary: ER membrane; consistent. Reason: The ER membrane location is experimental for S. pombe in UniProt (ECO:0000269|PubMed:16823372) and the record has four predicted TRANSMEM helices. Supporting Evidence: file:SCHPO/scs7/scs7-uniprot.txt Endoplasmic reticulum membrane {ECO:0000269|PubMed:16823372} file:SCHPO/scs7/scs7-uniprot.txt Multi-pass membrane protein {ECO:0000269|PubMed:16823372} file:SCHPO/scs7/scs7-uniprot.txt TRANSMEM 157..177 |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: ER membrane; consistent. Reason: The SubCell mapping rests on the UniProt ER membrane location, experimental for S. pombe (ECO:0000269|PubMed:16823372). Supporting Evidence: file:SCHPO/scs7/scs7-uniprot.txt Endoplasmic reticulum membrane {ECO:0000269|PubMed:16823372} file:SCHPO/scs7/scs7-uniprot.txt Multi-pass membrane protein {ECO:0000269|PubMed:16823372} |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000120 | TOO GENERAL | Summary: Broad parent; the specific ceramide and MIPC biosynthetic process terms are asserted in this review. Reason: True but uninformative. scs7 is an SCS7-subfamily fatty acid hydroxylase (InterPro IPR014430, behind this row) whose curated function, by similarity to S. cerevisiae SCS7 (ECO:0000250|UniProtKB:Q03529), is hydroxylation of the very long chain fatty acid of ceramides; GO:0046513 ceramide biosynthetic process, asserted in this review, entails lipid metabolic process. Family and by-similarity evidence. Supporting Evidence: file:SCHPO/scs7/scs7-uniprot.txt Ceramide hydroxylase involved in the hydroxylation of sphingolipid-associated very long chain fatty acids. file:SCHPO/scs7/scs7-uniprot.txt IPR014430; Scs7. |
| GO:0006675 mannosyl-inositol phosphorylceramide metabolic process | IMP PMID:20388730 Mannosylinositol phosphorylceramide is a major sphingolipid ... | ACCEPT | Summary: VLCFA 2-hydroxylation contributes to MIPC (curator, full text). Supporting Evidence: PMID:20388730 Analysis of the sphingolipid composition of wild-type cells confirmed that MIPC is the terminal and most abundant complex sphingolipid in S. pombe. |
| GO:0016020 membrane | IEA GO_REF:0000002 | TOO GENERAL | Summary: Generic membrane; the specific endoplasmic reticulum membrane location is asserted in this review. Reason: True but uninformative. scs7 is a multi-pass membrane protein localized to the ER membrane in S. pombe (ECO:0000269|PubMed:16823372) with four predicted transmembrane helices; GO:0005789 endoplasmic reticulum membrane, asserted in this review, entails membrane. Supporting Evidence: file:SCHPO/scs7/scs7-uniprot.txt Endoplasmic reticulum membrane {ECO:0000269|PubMed:16823372}; Multi-pass membrane protein {ECO:0000269|PubMed:16823372}. file:SCHPO/scs7/scs7-uniprot.txt TRANSMEM 157..177 |
| GO:0046513 ceramide biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference: ceramide modification. Reason: Ceramide modification (2-hydroxylation of the amide-linked VLCFA) is by similarity to S. cerevisiae SCS7 (ECO:0000250|UniProtKB:Q03529); not assayed in S. pombe. Supporting Evidence: file:SCHPO/scs7/scs7-uniprot.txt Postulated to hydroxylate the very long chain fatty acid of dihydroceramides and phytoceramides at C-2 file:SCHPO/scs7/scs7-uniprot.txt PATHWAY: Sphingolipid metabolism. |
| GO:0051999 mannosyl-inositol phosphorylceramide biosynthetic process | IMP PMID:20388730 Mannosylinositol phosphorylceramide is a major sphingolipid ... | ACCEPT | Summary: Hydroxylated ceramide feeds MIPC synthesis (curator, full text). Supporting Evidence: PMID:20388730 Analysis of the sphingolipid composition of wild-type cells confirmed that MIPC is the terminal and most abundant complex sphingolipid in S. pombe. |
| GO:0080132 fatty acid 2-hydroxylase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Fatty acid 2-hydroxylase activity on the ceramide VLCFA (PAINT/mapping). Reason: The 2-hydroxylase activity is by similarity to S. cerevisiae SCS7 (UniProt FUNCTION, ECO:0000250|UniProtKB:Q03529) and membership of the PANTHER fatty acid 2-hydroxylase subfamily and the SCS7 subfamily; it has not been assayed in S. pombe. UniProt cautions that the protein lacks the N-terminal cytochrome b5 domain, so its activity is unsure. The row is kept because the Zn(2+) dimetal-centre ligands of the catalytic core are retained (UniProt COFACTOR and BINDING features, by similarity), and the b5 domain supplies electrons rather than the active site. Supporting Evidence: file:SCHPO/scs7/scs7-uniprot.txt Ceramide hydroxylase involved in the hydroxylation of sphingolipid-associated very long chain fatty acids file:SCHPO/scs7/scs7-uniprot.txt PTHR12863:SF1; FATTY ACID 2-HYDROXYLASE file:SCHPO/scs7/scs7-uniprot.txt Belongs to the sterol desaturase family. SCS7 subfamily. |
| GO:0080132 fatty acid 2-hydroxylase activity | IEA GO_REF:0000002 | ACCEPT | Summary: Fatty acid 2-hydroxylase activity on the ceramide VLCFA (PAINT/mapping). Reason: The 2-hydroxylase activity is by similarity to S. cerevisiae SCS7 (UniProt FUNCTION, ECO:0000250|UniProtKB:Q03529) and membership of the PANTHER fatty acid 2-hydroxylase subfamily and the SCS7 subfamily; it has not been assayed in S. pombe. UniProt cautions that the protein lacks the N-terminal cytochrome b5 domain, so its activity is unsure. The row is kept because the Zn(2+) dimetal-centre ligands of the catalytic core are retained (UniProt COFACTOR and BINDING features, by similarity), and the b5 domain supplies electrons rather than the active site. Supporting Evidence: file:SCHPO/scs7/scs7-uniprot.txt Ceramide hydroxylase involved in the hydroxylation of sphingolipid-associated very long chain fatty acids file:SCHPO/scs7/scs7-uniprot.txt PTHR12863:SF1; FATTY ACID 2-HYDROXYLASE file:SCHPO/scs7/scs7-uniprot.txt Belongs to the sterol desaturase family. SCS7 subfamily. |
| GO:0102772 sphingolipid C4-monooxygenase activity | ISO GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISO transfer of sphingolipid C4-monooxygenase activity from S. cerevisiae SCS7. The term names C-4 hydroxylation of the sphingoid base, which in yeast is the Sur2 reaction; Scs7-family enzymes hydroxylate the amide-linked very long chain fatty acid at C-2. Reason: The donor is the true ortholog, S. cerevisiae SCS7 (SGD:S000004885), but its own annotation to this term is a mis-mapping. Haak et al. assign C-4 hydroxylation of the ceramide sphingoid moiety to Sur2p and very long chain fatty acid hydroxylation to Scs7p, and the S. pombe scs7 curated function (by similarity to Q03529) is C-2 hydroxylation of the fatty acyl chain. The ceramide-hydroxylase essence holds, but the C-4 position over-reaches; the fatty acid 2-hydroxylase activity is already annotated. Propagation Review Root cause: SOURCE BAD Failure modes: ROLE CONFLATION Sources checked: SGD:S000004885 SOURCE BAD S. cerevisiae SCS7, the true ortholog. Its own annotation to sphingolipid C4-monooxygenase activity is a mis-mapping (C-4 hydroxylation of the sphingoid base is the Sur2 activity; Scs7 is the fatty acyl 2-hydroxylase), so the transferred term is wrong for scs7 as well. Supporting Evidence: PMID:9368039 Sur2p is required for the hydroxylation of C-4 of the sphingoid moiety of ceramide, and Scs7p is required for the hydroxylation of the very long chain fatty acid. file:SCHPO/scs7/scs7-uniprot.txt Postulated to hydroxylate the very long chain fatty acid of dihydroceramides and phytoceramides at C-2. |
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