cut6 (SPAC56E4.04c) encodes the acetyl-CoA carboxylase (ACC, EC 6.4.1.2) of fission yeast, a large biotin-dependent multidomain enzyme that carries biotin carboxylase, biotin carboxyl carrier and carboxyltransferase activities on one polypeptide and is the orthologue of S. cerevisiae ACC1. It carboxylates acetyl-CoA to malonyl-CoA, the committed step of de novo fatty acid synthesis by the fas1/fas2 fatty acid synthase and the malonyl-CoA source for fatty acid elongation. cut6 is essential; temperature-sensitive cut6 mutants (named for the cell untimely torn phenotype) show unequal nuclear division with large and small daughter nuclei, a defect shared with fatty acid synthase mutants and attributed to insufficient lipid for nuclear envelope expansion during closed mitosis. The protein is cytosolic. S. pombe has no separate mitochondrial ACC paralogue comparable to budding-yeast HFA1.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003989 acetyl-CoA carboxylase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PANTHER PTN000429606 (ACC node; S. cerevisiae ACC1/HFA1, human ACACA/ACACB, mouse, rat, Arabidopsis donors). cut6 is the sole multidomain ACC of S. pombe and is essential. Core MF. Supporting Evidence: file:SCHPO/cut6/cut6-uniprot.txt Reaction=hydrogencarbonate + acetyl-CoA + ATP = malonyl-CoA + ADP + PMID:8769419 The cut6+ and lsd1+ genes are essential for viability and encode, respectively, acetyl CoA carboxylase and fatty acid synthetase, the key enzymes for fatty acid synthesis |
| GO:0003989 acetyl-CoA carboxylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (InterPro carboxyltransferase domains IPR013537/IPR049076, RHEA:11308, EC 6.4.1.2). Correct. Supporting Evidence: file:SCHPO/cut6/cut6-uniprot.txt Reaction=hydrogencarbonate + acetyl-CoA + ATP = malonyl-CoA + ADP + |
| GO:0003989 acetyl-CoA carboxylase activity | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from S. cerevisiae ACC1 (UniProtKB:Q00955), whose ACC activity is experimentally established. cut6 has the same BC-BCCP-CT architecture and is identified as acetyl-CoA carboxylase in the cut6 cloning study. Core MF. Supporting Evidence: PMID:8769419 The cut6+ and lsd1+ genes are essential for viability and encode, respectively, acetyl CoA carboxylase and fatty acid synthetase, the key enzymes for fatty acid synthesis file:SCHPO/cut6/cut6-uniprot.txt Carries out three functions: biotin carboxyl carrier protein, |
| GO:0004075 biotin carboxylase activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: IEA from RHEA:13501 / EC 6.3.4.14: the biotin carboxylase half-reaction of the BC domain. Correct but a partial reaction of the overall ACC activity; non-core, as in the S. cerevisiae ACC1 review. Supporting Evidence: file:SCHPO/cut6/cut6-uniprot.txt Reaction=N(6)-biotinyl-L-lysyl-[protein] + hydrogencarbonate + ATP = |
| GO:0004075 biotin carboxylase activity | ISO GO_REF:0000024 | KEEP AS NON CORE | Summary: ISO from S. cerevisiae ACC1 (SGD:S000005299). Partial reaction of ACC; non-core, consistent with ACC1. Supporting Evidence: file:SCHPO/cut6/cut6-uniprot.txt Reaction=N(6)-biotinyl-L-lysyl-[protein] + hydrogencarbonate + ATP = |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro biotin carboxylase/ATP-grasp domain mapping. ATP is the co-substrate of the biotin carboxylase step; non-core. Supporting Evidence: file:SCHPO/cut6/cut6-uniprot.txt Reaction=hydrogencarbonate + acetyl-CoA + ATP = malonyl-CoA + ADP + |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location (Cytoplasm, from the ORFeome data) keyword mapping. Correct. Supporting Evidence: file:SCHPO/cut6/cut6-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | UNDECIDED | Summary: IBA mitochondrion from PTN000429607, seeded by the mitochondrial S. cerevisiae paralogue HFA1 and by ACACB (outer mitochondrial membrane). In S. cerevisiae the equivalent row on cytosolic ACC1 was removed because HFA1 provides the mitochondrial pool. S. pombe, however, has a single ACC (cut6) and no HFA1 orthologue, and PomBase's fatty-acid GO-CAM (gomodel:678073a900002931) uses this IBA to place a second cut6 ACC activity in the mitochondrion supplying malonyl-CoA for mitochondrial FAS II. Dual targeting of cut6 is therefore biologically plausible but has not been shown (the ORFeome screen reports cytosol). Left undecided pending direct evidence. Reason: Plausible for the sole S. pombe ACC, but no experimental mitochondrial localization; node evidence derives from paralogues with dedicated mitochondrial roles. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome |
| GO:0005829 cytosol | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: ORFeome screen, cytosol. Matches cytosolic de novo fatty acid synthesis and the PomBase GO-CAM cytosolic cut6 activity. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome |
| GO:0006633 fatty acid biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA fatty acid biosynthetic process (PTN000429606). Malonyl-CoA formation is the committed step of fatty acid synthesis; cut6 is essential and its loss phenocopies FAS (fas2/lsd1) loss. Core BP. Supporting Evidence: PMID:8769419 The cut6+ and lsd1+ genes are essential for viability and encode, respectively, acetyl CoA carboxylase and fatty acid synthetase, the key enzymes for fatty acid synthesis PMID:8769419 A reduced level of fatty acid thus led to impaired separation of non-chromosomal nuclear components |
| GO:0006633 fatty acid biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro IPR013537 (ACC carboxyltransferase) mapping. Correct. Supporting Evidence: PMID:8769419 The cut6+ and lsd1+ genes are essential for viability and encode, respectively, acetyl CoA carboxylase and fatty acid synthetase, the key enzymes for fatty acid synthesis |
| GO:0016874 ligase activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro IPR011763 (ACC carboxyltransferase C-terminal) mapping to 'ligase activity', a distant parent of GO:0003989. True but uninformative; same call as in the S. cerevisiae ACC1 review. Supporting Evidence: file:SCHPO/cut6/cut6-uniprot.txt Reaction=hydrogencarbonate + acetyl-CoA + ATP = malonyl-CoA + ADP + |
| GO:0046872 metal ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro IPR011761 (ATP-grasp) mapping; UniProt records two Mn(2+) per subunit by similarity, used by the biotin carboxylase domain. Cofactor binding, non-core. Supporting Evidence: file:SCHPO/cut6/cut6-uniprot.txt Note=Binds 2 manganese ions per 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): cut6 ts mutants show the lsd (large and small daughter) nuclear-division defect, with asymmetric nuclear elongation; fatty acid shortage (cerulenin, lsd1/fas2 loss, rescued by palmitate) produces the same phenotype. S. pombe undergoes closed mitosis and must expand the nuclear envelope, so cut6 is required for mitotic nuclear membrane growth via lipid supply. This is a genuine but downstream consequence of malonyl-CoA/fatty acid supply; non-core. Supporting Evidence: PMID:8769419 A reduced level of fatty acid thus led to impaired separation of non-chromosomal nuclear components PMID:8769419 The cut6+ and lsd1+ genes are essential for viability and encode, respectively, acetyl CoA carboxylase and fatty acid synthetase, the key enzymes for fatty acid synthesis |
| GO:2001295 malonyl-CoA biosynthetic process | IC GO_REF:0000036 | ACCEPT | Summary: IC from GO:0003989: the ACC reaction forms malonyl-CoA. Correct; core BP. Supporting Evidence: file:SCHPO/cut6/cut6-uniprot.txt Reaction=hydrogencarbonate + acetyl-CoA + ATP = malonyl-CoA + ADP + |
| GO:2001295 malonyl-CoA biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway UPA00655 (malonyl-CoA from acetyl-CoA) mapping. Correct. Supporting Evidence: file:SCHPO/cut6/cut6-uniprot.txt PATHWAY: Lipid metabolism; malonyl-CoA biosynthesis; malonyl-CoA from |
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Download this section (compressed HTML)Q: Since S. pombe lacks an HFA1-like mitochondrial ACC, how is malonyl-CoA supplied to mitochondrial fatty acid synthesis (lipoic acid): is a fraction of cut6 imported into mitochondria (e.g. by alternative translation start), or is another enzyme responsible?
Experiment: Tag endogenous cut6 and assess mitochondrial import (fractionation, protease protection), and test whether lipoylation of mitochondrial enzymes depends on cut6 under permissive versus restrictive conditions in cut6-ts cells.
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