fas2 (SPAC4A8.11c; also known as lsd1) encodes the alpha subunit of the fission yeast type I fatty acid synthase (FAS), the orthologue of S. cerevisiae FAS2. Six fas2 alpha and six fas1 beta subunits form a ~2.2 MDa barrel-shaped alpha6beta6 complex. The alpha subunit carries the acyl carrier protein domain, the NADPH-dependent 3-oxoacyl-ACP reductase, the 3-oxoacyl-ACP synthase (condensing enzyme), and a C-terminal phosphopantetheinyl transferase that activates the ACP; the beta subunit supplies the acetyl- and malonyl/palmitoyl transferases, dehydratase and enoyl reductase. The complex converts acetyl-CoA, malonyl-CoA and NADPH to long-chain acyl-CoA in the cytosol. fas2 is essential; temperature-sensitive lsd1 alleles cause unequal (large and small daughter) nuclear division and accumulate abnormal very-long-chain phospholipids, both rescued by palmitate, reflecting the demand for fatty acids during nuclear envelope expansion in closed mitosis. In vitro DNA strand-exchange activity reported for purified FAS (p190/210) is regarded by its authors as unlikely to be physiological.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000036 acyl carrier activity | ISM GO_REF:0000050 | ACCEPT | Summary: ISM from InterPro IPR009081 (ACP-like domain). The N-terminal ACP domain of the alpha subunit carries the phosphopantetheine arm that shuttles intermediates between all eight active sites; PomBase models fas2 with this activity in the GO-CAM. Correct; core. Supporting Evidence: file:SCHPO/fas2/fas2-uniprot.txt Pfam; PF18325; Fas_alpha_ACP; 1. file:SCHPO/fas2/fas2-uniprot.txt protein] reductase, and 3-oxoacyl-[acyl-carrier-protein] synthase. This |
| GO:0000287 magnesium ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro 4'-phosphopantetheinyl transferase (ACPS) domain signatures. The PPT reaction is Mg2+-dependent; cofactor detail of the holo-ACP synthase activity. Non-core, as in FAS2 review. Supporting Evidence: file:SCHPO/fas2/fas2-uniprot.txt Pfam; PF01648; ACPS; 1. |
| GO:0004312 fatty acid synthase activity | IDA PMID:9693066 Cloning of the fatty acid synthetase beta subunit from fissi... | MODIFY | Summary: IDA contributes_to fatty acid synthase activity from the purified co-expressed Fas1/Fas2 complex. Activity is real; GO:0004312 (EC 2.3.1.85) is the animal-type activity releasing free fatty acid; the fungal alpha6beta6 FAS (EC 2.3.1.86) releases acyl-CoA, so GO:0004321 is the correct complex activity (as in the S. cerevisiae FAS2 review and the PomBase GO-CAM complex node). Reason: Fungal FAS synthesises acyl-CoA (EC 2.3.1.86). Proposed replacements: fatty-acyl-CoA synthase activity Supporting Evidence: PMID:9693066 The isolated FAS complex showed quite high specific activity, of more than 4000 mU/mg, suggesting complete purification file:SCHPO/fas2/fas2-uniprot.txt Reaction=acetyl-CoA + n malonyl-CoA + 2n NADPH + 4n H(+) = a long- |
| GO:0004312 fatty acid synthase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro IPR026025 (FAS alpha subunit) mapping to fatty acid synthase activity. GO:0004312 (EC 2.3.1.85) is the animal-type activity releasing free fatty acid; the fungal alpha6beta6 FAS (EC 2.3.1.86) releases acyl-CoA, so GO:0004321 is the correct complex activity (as in the S. cerevisiae FAS2 review and the PomBase GO-CAM complex node). Reason: Fungal FAS synthesises acyl-CoA. Proposed replacements: fatty-acyl-CoA synthase activity Supporting Evidence: file:SCHPO/fas2/fas2-uniprot.txt Reaction=acetyl-CoA + n malonyl-CoA + 2n NADPH + 4n H(+) = a long- |
| GO:0004315 3-oxoacyl-[acyl-carrier-protein] synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA (InterPro KS signatures, RHEA:22836, EC 2.3.1.41) for the ketoacyl synthase domain. Correct; core partial activity (the cerulenin target). Supporting Evidence: file:SCHPO/fas2/fas2-uniprot.txt Reaction=a fatty acyl-[ACP] + malonyl-[ACP] + H(+) = a 3-oxoacyl-[ACP] |
| GO:0004315 3-oxoacyl-[acyl-carrier-protein] synthase activity | ISO GO_REF:0000024 | ACCEPT | Summary: ISO from S. cerevisiae FAS2 (SGD:S000006152). Correct; used for fas2 in the PomBase GO-CAM. Supporting Evidence: file:SCHPO/fas2/fas2-uniprot.txt Reaction=a fatty acyl-[ACP] + malonyl-[ACP] + H(+) = a 3-oxoacyl-[ACP] PMID:11470243 The lsd1(+) gene is the homologue of the budding yeast FAS2 gene encoding the fatty acid synthase alpha-subunit |
| GO:0004316 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA (InterPro, RHEA:17397, EC 1.1.1.100) for the NADPH-dependent ketoacyl reductase domain. Correct; core. Supporting Evidence: file:SCHPO/fas2/fas2-uniprot.txt Reaction=a (3R)-hydroxyacyl-[ACP] + NADP(+) = a 3-oxoacyl-[ACP] + NADPH |
| GO:0004316 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity | ISO GO_REF:0000024 | ACCEPT | Summary: ISO from S. cerevisiae FAS2, whose alpha subunit carries the beta-ketoacyl reductase. Correct. Supporting Evidence: file:SCHPO/fas2/fas2-uniprot.txt Reaction=a (3R)-hydroxyacyl-[ACP] + NADP(+) = a 3-oxoacyl-[ACP] + NADPH PMID:11470243 The lsd1(+) gene is the homologue of the budding yeast FAS2 gene encoding the fatty acid synthase alpha-subunit |
| GO:0004321 fatty-acyl-CoA synthase activity | IEA GO_REF:0000003 | ACCEPT | Summary: IEA from EC 2.3.1.86. Correct overall activity of the alpha6beta6 complex to which fas2 contributes. Supporting Evidence: file:SCHPO/fas2/fas2-uniprot.txt Reaction=acetyl-CoA + n malonyl-CoA + 2n NADPH + 4n H(+) = a long- PMID:9693066 These results indicate that the FAS complex from S. pombe forms a heterododecameric alpha6beta6 structure |
| GO:0005829 cytosol | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: ORFeome screen, cytosol. Correct for the soluble FAS complex. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome |
| GO:0005835 fatty acid synthase complex | IDA PMID:9693066 Cloning of the fatty acid synthetase beta subunit from fissi... | ACCEPT | Summary: IDA: co-purified alpha6beta6 S. pombe FAS (2.1-2.4 MDa barrel). Core complex. Supporting Evidence: PMID:9693066 These results indicate that the FAS complex from S. pombe forms a heterododecameric alpha6beta6 structure PMID:9693066 We have developed a co-expression system of the FAS alpha and beta subunits by cotransformation of two expression vectors, containing the lsd1+/fas2+ gene and the fas1+ gene, into fission yeast cells |
| GO:0005835 fatty acid synthase complex | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro IPR026025 mapping. Correct. Supporting Evidence: PMID:9693066 These results indicate that the FAS complex from S. pombe forms a heterododecameric alpha6beta6 structure |
| GO:0005835 fatty acid synthase complex | IPI PMID:9693066 Cloning of the fatty acid synthetase beta subunit from fissi... | ACCEPT | Summary: IPI from co-expression/co-purification of fas2 (lsd1) with fas1. Correct. Supporting Evidence: PMID:9693066 We have developed a co-expression system of the FAS alpha and beta subunits by cotransformation of two expression vectors, containing the lsd1+/fas2+ gene and the fas1+ gene, into fission yeast cells PMID:9693066 These results indicate that the FAS complex from S. pombe forms a heterododecameric alpha6beta6 structure |
| GO:0006633 fatty acid biosynthetic process | IDA PMID:9693066 Cloning of the fatty acid synthetase beta subunit from fissi... | ACCEPT | Summary: IDA from the active purified complex. Correct; GO:0042759 is more specific. Supporting Evidence: PMID:9693066 The isolated FAS complex showed quite high specific activity, of more than 4000 mU/mg, suggesting complete purification |
| GO:0006633 fatty acid biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (ARBA, InterPro). Correct. Supporting Evidence: file:SCHPO/fas2/fas2-uniprot.txt Reaction=acetyl-CoA + n malonyl-CoA + 2n NADPH + 4n H(+) = a long- |
| GO:0008897 holo-[acyl-carrier-protein] synthase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro 4'-phosphopantetheinyl transferase domain signatures. The C-terminal PPT domain pantetheinylates the FAS ACP domain. Correct. Supporting Evidence: file:SCHPO/fas2/fas2-uniprot.txt Pfam; PF01648; ACPS; 1. |
| GO:0008897 holo-[acyl-carrier-protein] synthase activity | ISO GO_REF:0000024 | ACCEPT | Summary: ISO from S. cerevisiae FAS2, whose intrinsic PPTase self-activates the FAS ACP. Correct; in the PomBase GO-CAM. Supporting Evidence: file:SCHPO/fas2/fas2-uniprot.txt Pfam; PF01648; ACPS; 1. PMID:11470243 The lsd1(+) gene is the homologue of the budding yeast FAS2 gene encoding the fatty acid synthase alpha-subunit |
| GO:0016746 acyltransferase activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro IPR016039 (thiolase-like fold of the KS domain) mapping to 'acyltransferase activity'. True but uninformative parent of GO:0004315; non-core. Supporting Evidence: file:SCHPO/fas2/fas2-uniprot.txt Reaction=a fatty acyl-[ACP] + malonyl-[ACP] + H(+) = a 3-oxoacyl-[ACP] |
| GO:0042759 long-chain fatty acid biosynthetic process | IDA PMID:9693066 Cloning of the fatty acid synthetase beta subunit from fissi... | ACCEPT | Summary: IDA from the purified active complex. Core BP. Supporting Evidence: PMID:9693066 The isolated FAS complex showed quite high specific activity, of more than 4000 mU/mg, suggesting complete purification |
| GO:0042759 long-chain fatty acid biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro IPR026025 mapping. Correct. Supporting Evidence: file:SCHPO/fas2/fas2-uniprot.txt Reaction=acetyl-CoA + n malonyl-CoA + 2n NADPH + 4n H(+) = a long- |
| GO:0042759 long-chain fatty acid biosynthetic process | IMP PMID:11470243 Very-long-chain fatty acid-containing phospholipids accumula... | ACCEPT | Summary: IMP (Yokoyama et al. 2001): fas2 ts strains are rescued by palmitate and accumulate abnormal very-long-chain phospholipids at restrictive temperature, consistent with loss of de novo long-chain synthesis. Correct. Supporting Evidence: PMID:11470243 Rescue of the fas2 strains by addition of palmitate to the medium at restrictive temperature was accompanied by disappearance of these abnormal phospholipids PMID:11470243 The lsd1(+) gene is the homologue of the budding yeast FAS2 gene encoding the fatty acid synthase alpha-subunit |
| GO:0101026 mitotic nuclear membrane biogenesis | IMP PMID:8769419 Aberrant mitosis in fission yeast mutants defective in fatty... | KEEP AS NON CORE | Summary: IMP (Saitoh et al. 1996): lsd1/fas2 disruption and ts alleles cause the large-and-small-daughter nuclear division defect, suppressed by palmitate and phenocopied by cerulenin. Nuclear envelope expansion in the closed mitosis of S. pombe requires de novo fatty acids, so this is a genuine but downstream consequence of FAS activity. Non-core. Supporting Evidence: PMID:8769419 A reduced level of fatty acid thus led to impaired separation of non-chromosomal nuclear components PMID:8769419 Palmitate in medium fully suppressed the phenotypes of lsd1 |
| GO:1900535 palmitic acid biosynthetic process | IMP PMID:11470243 Very-long-chain fatty acid-containing phospholipids accumula... | KEEP AS NON CORE | Summary: IMP palmitic acid biosynthetic process: fas2 mutants are rescued by exogenous palmitate. FAS makes palmitoyl- and stearoyl-CoA; the term is acceptable as a specific long-chain product, though the released product is acyl-CoA rather than free palmitate. Keep as non-core detail of GO:0042759. Supporting Evidence: PMID:11470243 Rescue of the fas2 strains by addition of palmitate to the medium at restrictive temperature was accompanied by disappearance of these abnormal phospholipids |
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Download this section (compressed HTML)Q: Why do fas2 ts alleles that only slightly affect FAS activity in vitro accumulate melissoyl (C30) phospholipids; does impaired FAS shift malonyl-CoA toward the ER elongases (elo1/elo2)?
Experiment: Profile acyl-CoA chain lengths and elongase (elo1/elo2) dependence of the C30 phospholipid accumulation in fas2 ts strains with and without elongase deletions.
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