SPAC4G9.15 (PomBase ifa38) encodes the very-long-chain 3-oxoacyl-CoA reductase (3-ketoacyl-CoA reductase, KAR; EC 1.1.1.330) of the fission yeast ER fatty-acid elongation system, a short-chain dehydrogenase/reductase (SDR) anchored in the endoplasmic reticulum membrane and orthologous to S. cerevisiae IFA38 and human HSD17B12. It catalyses the NADPH-dependent reduction of the 3-oxoacyl-CoA produced by the elo1/elo2 condensing enzymes to (3R)-3-hydroxyacyl-CoA, the second step of each two-carbon elongation cycle, which is completed by the dehydratase phs1 and the enoyl reductase tsc13. The very-long-chain fatty acids made by this cycle are the acyl chains of ceramide and sphingolipids. Function in S. pombe is inferred from orthology (HAMAP MF_03107) and genome-wide ER localisation; no S. pombe-specific biochemistry has been reported.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005783 endoplasmic reticulum | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: ORFeome-wide YFP localisation (Matsuyama et al. 2006) placed SPAC4G9.15 in the ER, consistent with an ER-membrane-anchored elongase component. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins file:SCHPO/ifa38/ifa38-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from node PTN002454146 (donors S. cerevisiae IFA38 and C. elegans let-767). ER residence of the elongase ketoreductase is conserved and matches the S. pombe HDA localisation. Supporting Evidence: file:SCHPO/ifa38/ifa38-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO from IPR027533 (3-ketoacyl-CoA reductase, fungi); correct, less precise than ER membrane. Supporting Evidence: file:SCHPO/ifa38/ifa38-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA from UniProt subcellular location (SL-0097) and UniRule UR000106466 (HAMAP MF_03107). Correct: single-pass ER membrane protein. Supporting Evidence: file:SCHPO/ifa38/ifa38-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0006633 fatty acid biosynthetic process | IEA GO_REF:0000041 | MODIFY | Summary: UniPathway mapping (UPA00094, fatty acid biosynthesis) gives the broad parent. The enzyme acts in microsomal elongation to very-long-chain fatty acids, not in de novo synthesis by FAS. Reason: More precise process available; same call as for S. cerevisiae IFA38. Proposed replacements: very long-chain fatty acid biosynthetic process Supporting Evidence: file:SCHPO/ifa38/ifa38-uniprot.txt ketoacyl-CoA intermediate that is formed in each cycle of fatty acid |
| GO:0030148 sphingolipid biosynthetic process | ISO GO_REF:0000024 | KEEP AS NON CORE | Summary: PomBase ISO from S. cerevisiae IFA38, whose mutants are defective in sphingolipid synthesis. The ketoreductase supplies VLCFA for ceramide; sphingolipid synthesis is a downstream consequence rather than the step the enzyme performs. Reason: Downstream process of the VLCFA product; kept as non-core, as for IFA38. Supporting Evidence: file:SCHPO/ifa38/ifa38-uniprot.txt elongation. VLCFAs serve as precursors for ceramide and sphingolipids. |
| GO:0030497 fatty acid elongation | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from node PTN002454146 (donors S. cerevisiae IFA38 and C. elegans let-767). Fatty acid elongation is the cycle this reductase serves. Supporting Evidence: file:SCHPO/ifa38/ifa38-uniprot.txt ketoacyl-CoA intermediate that is formed in each cycle of fatty acid |
| GO:0030497 fatty acid elongation | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA from IPR027533 and UniRule UR000106466; correct. Supporting Evidence: file:SCHPO/ifa38/ifa38-uniprot.txt ketoacyl-CoA intermediate that is formed in each cycle of fatty acid |
| GO:0045703 ketoreductase activity | IEA GO_REF:0000120 | MODIFY | Summary: IPR027533/UniRule mapping to generic 'ketoreductase activity'. Correct in kind but the specific activity is reduction of very-long-chain 3-oxoacyl-CoA (EC 1.1.1.330). Reason: A precise child term exists and is already annotated by Rhea mapping. Proposed replacements: very-long-chain 3-oxoacyl-CoA reductase activity Supporting Evidence: file:SCHPO/ifa38/ifa38-uniprot.txt Reaction=a very-long-chain (3R)-3-hydroxyacyl-CoA + NADP(+) = a very- |
| GO:0045703 ketoreductase activity | ISO GO_REF:0000024 | MODIFY | Summary: PomBase ISO from S. cerevisiae IFA38 to generic 'ketoreductase activity'; the S. cerevisiae review replaces this with the specific very-long-chain 3-oxoacyl-CoA reductase term. Reason: Use the precise activity term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: SGD:S000000363 · S000000363 SUPPORTS TRANSFER IFA38 ortholog transfer is sound; only the term is too general. Proposed replacements: very-long-chain 3-oxoacyl-CoA reductase activity Supporting Evidence: file:SCHPO/ifa38/ifa38-uniprot.txt Reaction=a very-long-chain (3R)-3-hydroxyacyl-CoA + NADP(+) = a very- |
| GO:0141040 very-long-chain 3-oxoacyl-CoA reductase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA from RHEA:48680 / EC 1.1.1.330 (HAMAP MF_03107). This is the core activity; also used for this protein in the PomBase GO-CAM 678073a900002931. Supporting Evidence: file:SCHPO/ifa38/ifa38-uniprot.txt Reaction=a very-long-chain (3R)-3-hydroxyacyl-CoA + NADP(+) = a very- file:SCHPO/ifa38/ifa38-uniprot.txt ketoacyl-CoA intermediate that is formed in each cycle of fatty acid |
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Download this section (compressed HTML)Experiment: Assay NADPH-dependent 3-ketoacyl-CoA reduction in microsomes from an SPAC4G9.15 deletion or depletion strain to test whether it is the sole elongase ketoreductase in S. pombe (S. cerevisiae retains residual Ayr1 activity).
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