HFA1 (YMR207C) encodes the mitochondrial acetyl-CoA carboxylase of S. cerevisiae, a paralog of the cytosolic enzyme ACC1 (54% identity) with the same biotin carboxylase, biotin carboxyl carrier and carboxyltransferase domain organisation. Hfa1 carboxylates acetyl-CoA to malonyl-CoA (EC 6.4.1.2) inside mitochondria, supplying the malonyl-CoA used by the type II mitochondrial fatty acid synthase (Mct1, Cem1, Oar1, Htd2, Etr1, Acp1), whose principal product is the octanoyl-ACP precursor of lipoic acid. hfa1 null mutants fail to grow on non-fermentable carbon sources and have less than 10% of normal lipoic acid, resembling mtFAS mutants. Its N-terminal mitochondrial targeting sequence, encoded upstream of the first in-frame AUG and apparently translated from a non-AUG start, is required for function. When the targeting sequence is removed, Hfa1 can replace Acc1 in the cytosol, showing the two isozymes are catalytically equivalent but compartmentally specialised.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003989 acetyl-CoA carboxylase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from eukaryotic ACC node PTN000429606. Hfa1 is a full-length multidomain ACC; Hoja et al. 2004 showed it restores ACC activity when expressed in acc1 mutants. Core MF. Supporting Evidence: PMID:14761959 Expression of HFA1 under the control of the ACC1 promoter restored cellular ACC activity in ACC1-defective yeast mutants to wild type levels file:yeast/HFA1/HFA1-uniprot.txt Reaction=hydrogencarbonate + acetyl-CoA + ATP = malonyl-CoA + ADP + |
| GO:0003989 acetyl-CoA carboxylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA via RHEA:11308 / EC 6.4.1.2 and ACC InterPro signatures. Correct for Hfa1. Supporting Evidence: file:yeast/HFA1/HFA1-uniprot.txt Reaction=hydrogencarbonate + acetyl-CoA + ATP = malonyl-CoA + ADP + |
| GO:0003989 acetyl-CoA carboxylase activity | IGI PMID:14761959 HFA1 encoding an organelle-specific acetyl-CoA carboxylase c... | ACCEPT | Summary: IGI with ACC1 (Hoja et al. 2004): HFA1 expressed from the ACC1 promoter restores wild-type ACC activity in ACC1-defective mutants. Direct support for the catalytic activity; core MF. Supporting Evidence: PMID:14761959 Expression of HFA1 under the control of the ACC1 promoter restored cellular ACC activity in ACC1-defective yeast mutants to wild type levels |
| GO:0003989 acetyl-CoA carboxylase activity | ISS PMID:7906156 Identification of a Saccharomyces cerevisiae gene closely re... | ACCEPT | Summary: ISS (Kearsey 1993) from close similarity of HFA1 to ACC1/FAS3. Later confirmed experimentally (Hoja et al. 2004). Supporting Evidence: PMID:14761959 HFA1 encodes a specific mitochondrial acetyl-CoA carboxylase providing malonyl-CoA for intraorganellar fatty acid and, in particular, lipoic acid synthesis file:yeast/HFA1/HFA1-uniprot.txt Reaction=hydrogencarbonate + acetyl-CoA + ATP = malonyl-CoA + ADP + |
| GO:0003989 acetyl-CoA carboxylase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-10 (fatty acid biosynthesis, initial steps). The ACC activity is correct, but YeastPathways places Hfa1 in the cytosolic FAS pathway; in vivo Hfa1 supplies malonyl-CoA inside mitochondria for mtFAS. MF accepted; compartment wrong (see cytosol rows). Supporting Evidence: file:yeast/HFA1/HFA1-uniprot.txt Reaction=hydrogencarbonate + acetyl-CoA + ATP = malonyl-CoA + ADP + PMID:14761959 HFA1 encodes a specific mitochondrial acetyl-CoA carboxylase providing malonyl-CoA for intraorganellar fatty acid and, in particular, lipoic acid synthesis |
| GO:0003989 acetyl-CoA carboxylase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-5962 (superpathway of fatty acid biosynthesis, saturated and unsaturated). The ACC activity is correct, but YeastPathways places Hfa1 in the cytosolic FAS pathway; in vivo Hfa1 supplies malonyl-CoA inside mitochondria for mtFAS. MF accepted; compartment wrong (see cytosol rows). Supporting Evidence: file:yeast/HFA1/HFA1-uniprot.txt Reaction=hydrogencarbonate + acetyl-CoA + ATP = malonyl-CoA + ADP + PMID:14761959 HFA1 encodes a specific mitochondrial acetyl-CoA carboxylase providing malonyl-CoA for intraorganellar fatty acid and, in particular, lipoic acid synthesis |
| GO:0003989 acetyl-CoA carboxylase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-6336 (superpathway of fatty acid biosynthesis, saturated). The ACC activity is correct, but YeastPathways places Hfa1 in the cytosolic FAS pathway; in vivo Hfa1 supplies malonyl-CoA inside mitochondria for mtFAS. MF accepted; compartment wrong (see cytosol rows). Supporting Evidence: file:yeast/HFA1/HFA1-uniprot.txt Reaction=hydrogencarbonate + acetyl-CoA + ATP = malonyl-CoA + ADP + PMID:14761959 HFA1 encodes a specific mitochondrial acetyl-CoA carboxylase providing malonyl-CoA for intraorganellar fatty acid and, in particular, lipoic acid synthesis |
| GO:0004075 biotin carboxylase activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: IEA via RHEA:13501 / EC 6.3.4.14 (biotin carboxylase half-reaction of the BC domain). Correct domain-level activity, subsumed by ACC activity. Reason: Partial (domain) activity subsumed by acetyl-CoA carboxylase activity. Supporting Evidence: file:yeast/HFA1/HFA1-uniprot.txt Reaction=N(6)-biotinyl-L-lysyl-[protein] + hydrogencarbonate + ATP = |
| GO:0004075 biotin carboxylase activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from Arabidopsis ACC1 (O04983). Hfa1 carries a conserved BC domain; correct domain-level activity, subsumed by ACC activity. Reason: Partial (domain) activity subsumed by acetyl-CoA carboxylase activity. Supporting Evidence: file:yeast/HFA1/HFA1-uniprot.txt Reaction=N(6)-biotinyl-L-lysyl-[protein] + hydrogencarbonate + ATP = |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: IEA from ATP-grasp/CPS ATP-binding InterPro domains. ATP is a substrate of the BC reaction; correct but implied by the catalytic MF. Reason: Substrate binding implied by the catalytic activity. Supporting Evidence: file:yeast/HFA1/HFA1-uniprot.txt Reaction=hydrogencarbonate + acetyl-CoA + ATP = malonyl-CoA + ADP + |
| GO:0005737 cytoplasm | HDA PMID:22842922 Dissecting DNA damage response pathways by analysing protein... | MARK AS OVER ANNOTATED | Summary: HDA (Tkach et al. 2012 GFP localisation screen) scoring Hfa1-GFP as cytoplasmic. Hfa1 is mitochondrial by fractionation, and its MTS is encoded upstream of the first in-frame AUG (non-AUG initiation); a tagged allele expressed from the annotated ORF may lose the MTS and mislocalise. No cytosolic function of native Hfa1 is known. Reason: Conflicts with low-throughput fractionation; plausible tagging/initiation artefact. Supporting Evidence: PMID:22842922 Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. PMID:14761959 the HFA1-encoded protein was specifically assigned by Western blotting of appropriate cell fractions to the mitochondrial compartment file:yeast/HFA1/HFA1-uniprot.txt required for function and proper subcellular location. May be |
| GO:0005739 mitochondrion | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: HDA (PMID:14562095) detecting Hfa1 in mitochondria; consistent with fractionation data. Supporting Evidence: PMID:14562095 Global analysis of protein localization in budding yeast. PMID:14761959 the HFA1-encoded protein was specifically assigned by Western blotting of appropriate cell fractions to the mitochondrial compartment |
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | ACCEPT | Summary: HDA (PMID:14576278) detecting Hfa1 in mitochondria; consistent with fractionation data. Supporting Evidence: PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. PMID:14761959 the HFA1-encoded protein was specifically assigned by Western blotting of appropriate cell fractions to the mitochondrial compartment |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: HDA (PMID:16823961) detecting Hfa1 in mitochondria; consistent with fractionation data. Supporting Evidence: PMID:16823961 A total of 851 different proteins (PROMITO dataset) were identified PMID:14761959 the HFA1-encoded protein was specifically assigned by Western blotting of appropriate cell fractions to the mitochondrial compartment |
| GO:0005739 mitochondrion | HDA PMID:22842922 Dissecting DNA damage response pathways by analysing protein... | ACCEPT | Summary: HDA (PMID:22842922) detecting Hfa1 in mitochondria; consistent with fractionation data. Supporting Evidence: PMID:22842922 Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. PMID:14761959 the HFA1-encoded protein was specifically assigned by Western blotting of appropriate cell fractions to the mitochondrial compartment |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (is_active_in) from mitochondrial ACC node PTN000429607 (Hfa1 itself, human ACACB, rodent Acacb). Correct for Hfa1. Supporting Evidence: PMID:14761959 the HFA1-encoded protein was specifically assigned by Western blotting of appropriate cell fractions to the mitochondrial compartment |
| GO:0005739 mitochondrion | IDA PMID:14761959 HFA1 encoding an organelle-specific acetyl-CoA carboxylase c... | ACCEPT | Summary: IDA (Hoja et al. 2004): Western blotting of cell fractions places Hfa1 in mitochondria, and the MTS is required for function. Core location. Supporting Evidence: PMID:14761959 the HFA1-encoded protein was specifically assigned by Western blotting of appropriate cell fractions to the mitochondrial compartment PMID:14761959 Removal of the mitochondrial targeting sequence abolished the competence of HFA1 DNA to complement hfal null mutants |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (Mitochondrion). Correct. Supporting Evidence: file:yeast/HFA1/HFA1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion PMID:14761959 the HFA1-encoded protein was specifically assigned by Western blotting of appropriate cell fractions to the mitochondrial compartment |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: RCA (is_active_in) from YeastPathways PWY3O-10 (fatty acid biosynthesis, initial steps) placing Hfa1 in the cytosolic fatty acid pathway. Native Hfa1 is a mitochondrial matrix enzyme; the cytosolic ACC is Acc1. Only an artificial MTS-deleted Hfa1 acts in the cytosol. Supporting Evidence: PMID:14761959 the HFA1-encoded protein was specifically assigned by Western blotting of appropriate cell fractions to the mitochondrial compartment PMID:14761959 HFA1 encodes a specific mitochondrial acetyl-CoA carboxylase providing malonyl-CoA for intraorganellar fatty acid and, in particular, lipoic acid synthesis PMID:14761959 Removal of the mitochondrial targeting sequence abolished the competence of HFA1 DNA to complement hfal null mutants |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: RCA (is_active_in) from YeastPathways PWY3O-5962 (superpathway of fatty acid biosynthesis, saturated and unsaturated) placing Hfa1 in the cytosolic fatty acid pathway. Native Hfa1 is a mitochondrial matrix enzyme; the cytosolic ACC is Acc1. Only an artificial MTS-deleted Hfa1 acts in the cytosol. Supporting Evidence: PMID:14761959 the HFA1-encoded protein was specifically assigned by Western blotting of appropriate cell fractions to the mitochondrial compartment PMID:14761959 HFA1 encodes a specific mitochondrial acetyl-CoA carboxylase providing malonyl-CoA for intraorganellar fatty acid and, in particular, lipoic acid synthesis PMID:14761959 Removal of the mitochondrial targeting sequence abolished the competence of HFA1 DNA to complement hfal null mutants |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: RCA (is_active_in) from YeastPathways PWY3O-6336 (superpathway of fatty acid biosynthesis, saturated) placing Hfa1 in the cytosolic fatty acid pathway. Native Hfa1 is a mitochondrial matrix enzyme; the cytosolic ACC is Acc1. Only an artificial MTS-deleted Hfa1 acts in the cytosol. Supporting Evidence: PMID:14761959 the HFA1-encoded protein was specifically assigned by Western blotting of appropriate cell fractions to the mitochondrial compartment PMID:14761959 HFA1 encodes a specific mitochondrial acetyl-CoA carboxylase providing malonyl-CoA for intraorganellar fatty acid and, in particular, lipoic acid synthesis PMID:14761959 Removal of the mitochondrial targeting sequence abolished the competence of HFA1 DNA to complement hfal null mutants |
| GO:0006633 fatty acid biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from eukaryotic ACC node. Hfa1 provides malonyl-CoA for mitochondrial type II fatty acid synthesis; correct. Supporting Evidence: PMID:14761959 HFA1 encodes a specific mitochondrial acetyl-CoA carboxylase providing malonyl-CoA for intraorganellar fatty acid and, in particular, lipoic acid synthesis PMID:14761959 the phenotype of hfa1Delta disruptants resembles that of mitochondrial fatty-acid synthase mutants |
| GO:0006633 fatty acid biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: IEA from InterPro IPR013537 (ACC central domain). Correct (mitochondrial FAS). Supporting Evidence: PMID:14761959 HFA1 encodes a specific mitochondrial acetyl-CoA carboxylase providing malonyl-CoA for intraorganellar fatty acid and, in particular, lipoic acid synthesis |
| GO:0006633 fatty acid biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-10 (fatty acid biosynthesis, initial steps). Hfa1 does participate in fatty acid biosynthesis, but in the mitochondrial (mtFAS) pathway rather than the cytosolic one; the BP term itself is correct. Supporting Evidence: PMID:14761959 HFA1 encodes a specific mitochondrial acetyl-CoA carboxylase providing malonyl-CoA for intraorganellar fatty acid and, in particular, lipoic acid synthesis PMID:14761959 the phenotype of hfa1Delta disruptants resembles that of mitochondrial fatty-acid synthase mutants |
| GO:0006633 fatty acid biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-5962 (superpathway of fatty acid biosynthesis, saturated and unsaturated). Hfa1 does participate in fatty acid biosynthesis, but in the mitochondrial (mtFAS) pathway rather than the cytosolic one; the BP term itself is correct. Supporting Evidence: PMID:14761959 HFA1 encodes a specific mitochondrial acetyl-CoA carboxylase providing malonyl-CoA for intraorganellar fatty acid and, in particular, lipoic acid synthesis PMID:14761959 the phenotype of hfa1Delta disruptants resembles that of mitochondrial fatty-acid synthase mutants |
| GO:0016874 ligase activity | IEA GO_REF:0000120 | TOO GENERAL | Summary: IEA (ARBA00028597 / IPR011763). ACC is a ligase (EC 6.4.1.2); correct but uninformative. Reason: Uninformative parent of the core MF. Supporting Evidence: file:yeast/HFA1/HFA1-uniprot.txt Reaction=hydrogencarbonate + acetyl-CoA + ATP = malonyl-CoA + ADP + |
| GO:0019367 fatty acid elongation, saturated fatty acid | RCA GO_REF:0000123 | MARK AS OVER ANNOTATED | Summary: RCA from YeastPathways PWY3O-6336 (superpathway of fatty acid biosynthesis, saturated), a cytosolic superpathway (palmitate to stearate). Hfa1 is mitochondrial and feeds mtFAS, whose main product is the octanoyl lipoate precursor; it has no demonstrated role in cytosolic saturated fatty acid elongation. Reason: Inherited from a cytosolic superpathway that Hfa1 does not participate in. Supporting Evidence: PMID:14761959 HFA1 encodes a specific mitochondrial acetyl-CoA carboxylase providing malonyl-CoA for intraorganellar fatty acid and, in particular, lipoic acid synthesis PMID:14761959 the phenotype of hfa1Delta disruptants resembles that of mitochondrial fatty-acid synthase mutants |
| GO:0042759 long-chain fatty acid biosynthetic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: IEA from ARBA00034980 rule (long-chain FA biosynthesis for ACCs). Appropriate for Acc1, but Hfa1 feeds mitochondrial FAS, which mainly makes the octanoyl precursor of lipoic acid. Reason: Rule-based transfer from the cytosolic ACC role. Supporting Evidence: PMID:14761959 HFA1 encodes a specific mitochondrial acetyl-CoA carboxylase providing malonyl-CoA for intraorganellar fatty acid and, in particular, lipoic acid synthesis PMID:14761959 the phenotype of hfa1Delta disruptants resembles that of mitochondrial fatty-acid synthase mutants |
| GO:0042759 long-chain fatty acid biosynthetic process | IGI PMID:14761959 HFA1 encoding an organelle-specific acetyl-CoA carboxylase c... | MARK AS OVER ANNOTATED | Summary: IGI with ACC1 (Hoja et al. 2004): MTS-deleted Hfa1 rescues the acc1 fatty-acid defect. This shows Hfa1 can catalyse ACC in an artificial cytosolic context; native Hfa1 provides malonyl-CoA for mitochondrial FAS, whose main output is octanoyl-ACP for lipoic acid, not bulk long-chain fatty acids. Reason: Rescue by an engineered cytosolic variant does not reflect the native role. Supporting Evidence: PMID:14761959 the signal sequence-free HFA1 gene complemented the mutational loss of cytoplasmic acetyl-CoA carboxylase PMID:14761959 HFA1 encodes a specific mitochondrial acetyl-CoA carboxylase providing malonyl-CoA for intraorganellar fatty acid and, in particular, lipoic acid synthesis |
| GO:0046872 metal ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: IEA from ATP-grasp domain (IPR011761); metal (Mn2+/Mg2+) binding for ATP-dependent carboxylation. Correct but uninformative. Reason: Cofactor binding implied by the catalytic activity. Supporting Evidence: file:yeast/HFA1/HFA1-uniprot.txt Reaction=N(6)-biotinyl-L-lysyl-[protein] + hydrogencarbonate + ATP = |
| GO:2001295 malonyl-CoA biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: IEA from UniPathway UPA00655 (malonyl-CoA from acetyl-CoA). Exactly the process Hfa1 performs in mitochondria; core BP. Supporting Evidence: file:yeast/HFA1/HFA1-uniprot.txt PATHWAY: Lipid metabolism; malonyl-CoA biosynthesis; malonyl-CoA from file:yeast/HFA1/HFA1-uniprot.txt production of the mitochondrial malonyl-CoA, used for the biosynthesis |
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Download this section (compressed HTML)Q: Which non-AUG codon initiates Hfa1 translation, and is a cytosolic (MTS-less) Hfa1 isoform ever produced in vivo?
Q: Is Hfa1 activity regulated by phosphorylation (e.g. Snf1) like Acc1, linking mitochondrial lipoate synthesis to nutrient status?
Experiment: Ribosome profiling / N-terminal proteomics of Hfa1 to define the translation start site and whether a cytosolic isoform exists.
Mitochondrial acetyl-coenzyme A carboxylase; catalyzes production of malonyl-CoA in mitochondrial fatty acid biosynthesis; relocalizes from mitochondrion to cytoplasm upon DNA replication stress; genetic and comparative analysis suggests that translation begins at a non-canonical (Ile) start codon at -372 relative to the annotated start codon
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