OAR1 (YKL055C) encodes the mitochondrial NADPH-dependent 3-oxoacyl-[acyl-carrier-protein] reductase (FabG-like short-chain dehydrogenase/reductase, EC 1.1.1.100) of S. cerevisiae. It reduces 3-oxoacyl-ACP to (3R)-3-hydroxyacyl-ACP, the first reductive step of each cycle of the type II mitochondrial fatty acid synthase (with Hfa1, Mct1, Cem1, Htd2, Etr1 and Acp1). mtFAS produces octanoyl-ACP for lipoic acid synthesis and other acyl chains required for respiratory function. oar1 null mutants are respiratory deficient with reduced lipoic acid, a defect rescued only by co-expression of both subunits of the human heterotetrameric mitochondrial ketoacyl reductase (HSD17B8 and CBR4).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004316 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity | IDA PMID:19571038 17beta-hydroxysteroid dehydrogenase type 8 and carbonyl redu... | ACCEPT | Summary: IDA (Chen et al. 2009): in this study of the human mitochondrial KAR the yeast Oar1p is described as an NADPH-dependent 3-oxoacyl-ACP reductase; the abstract-only cache does not show the yeast assay, so defer to the curator. Core MF. Supporting Evidence: PMID:19571038 although HsKAR is NADH dependent, whereas FabG and Oar1p are NADPH dependent PMID:19571038 they rescue the respiratory deficiency and restore the lipoic acid content of oar1Delta cells |
| GO:0004316 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA via RHEA:17397 / EC 1.1.1.100. Correct for Oar1. Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt Reaction=a (3R)-hydroxyacyl-[ACP] + NADP(+) = a 3-oxoacyl-[ACP] + NADPH |
| GO:0004316 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity | IMP PMID:9388293 Two genes of the putative mitochondrial fatty acid synthase ... | ACCEPT | Summary: IMP (Schneider et al. 1997): OAR1 identified by homology to bacterial FabG, and its disruption causes respiratory deficiency like other mtFAS mutants. Consistent with the activity; core MF. Supporting Evidence: PMID:9388293 homologous to bacterial 3-oxoacyl-(acyl carrier protein) reductases and to malonyl-CoA:ACP-transferases, respectively PMID:9388293 We disrupted these two genes which in both cases led to a respiratory deficient phenotype |
| GO:0004316 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways FASYN-ELONG2-PWY (fatty acid elongation (saturated, ACP-bound)). The 3-oxoacyl-ACP reductase activity is correct for Oar1, but YeastPathways places it in a cytosolic FAS pathway; the cytosolic KR step is carried out by the KR domain of Fas2, while Oar1 acts in mitochondrial FAS. MF accepted; compartment wrong. Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt Reaction=a (3R)-hydroxyacyl-[ACP] + NADP(+) = a 3-oxoacyl-[ACP] + NADPH PMID:19571038 although HsKAR is NADH dependent, whereas FabG and Oar1p are NADPH dependent |
| GO:0004316 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY-5971-1 (myristate biosynthesis). The 3-oxoacyl-ACP reductase activity is correct for Oar1, but YeastPathways places it in a cytosolic FAS pathway; the cytosolic KR step is carried out by the KR domain of Fas2, while Oar1 acts in mitochondrial FAS. MF accepted; compartment wrong. Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt Reaction=a (3R)-hydroxyacyl-[ACP] + NADP(+) = a 3-oxoacyl-[ACP] + NADPH PMID:19571038 although HsKAR is NADH dependent, whereas FabG and Oar1p are NADPH dependent |
| GO:0004316 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-10 (fatty acid biosynthesis, initial steps). The 3-oxoacyl-ACP reductase activity is correct for Oar1, but YeastPathways places it in a cytosolic FAS pathway; the cytosolic KR step is carried out by the KR domain of Fas2, while Oar1 acts in mitochondrial FAS. MF accepted; compartment wrong. Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt Reaction=a (3R)-hydroxyacyl-[ACP] + NADP(+) = a 3-oxoacyl-[ACP] + NADPH PMID:19571038 although HsKAR is NADH dependent, whereas FabG and Oar1p are NADPH dependent |
| GO:0004316 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-355 (stearate biosynthesis III (fungi)). The 3-oxoacyl-ACP reductase activity is correct for Oar1, but YeastPathways places it in a cytosolic FAS pathway; the cytosolic KR step is carried out by the KR domain of Fas2, while Oar1 acts in mitochondrial FAS. MF accepted; compartment wrong. Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt Reaction=a (3R)-hydroxyacyl-[ACP] + NADP(+) = a 3-oxoacyl-[ACP] + NADPH PMID:19571038 although HsKAR is NADH dependent, whereas FabG and Oar1p are NADPH dependent |
| GO:0004316 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-5962 (superpathway of fatty acid biosynthesis, saturated and unsaturated). The 3-oxoacyl-ACP reductase activity is correct for Oar1, but YeastPathways places it in a cytosolic FAS pathway; the cytosolic KR step is carried out by the KR domain of Fas2, while Oar1 acts in mitochondrial FAS. MF accepted; compartment wrong. Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt Reaction=a (3R)-hydroxyacyl-[ACP] + NADP(+) = a 3-oxoacyl-[ACP] + NADPH PMID:19571038 although HsKAR is NADH dependent, whereas FabG and Oar1p are NADPH dependent |
| GO:0004316 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-6336 (superpathway of fatty acid biosynthesis, saturated). The 3-oxoacyl-ACP reductase activity is correct for Oar1, but YeastPathways places it in a cytosolic FAS pathway; the cytosolic KR step is carried out by the KR domain of Fas2, while Oar1 acts in mitochondrial FAS. MF accepted; compartment wrong. Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt Reaction=a (3R)-hydroxyacyl-[ACP] + NADP(+) = a 3-oxoacyl-[ACP] + NADPH PMID:19571038 although HsKAR is NADH dependent, whereas FabG and Oar1p are NADPH dependent |
| GO:0004316 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-8514 (palmitate biosynthesis). The 3-oxoacyl-ACP reductase activity is correct for Oar1, but YeastPathways places it in a cytosolic FAS pathway; the cytosolic KR step is carried out by the KR domain of Fas2, while Oar1 acts in mitochondrial FAS. MF accepted; compartment wrong. Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt Reaction=a (3R)-hydroxyacyl-[ACP] + NADP(+) = a 3-oxoacyl-[ACP] + NADPH PMID:19571038 although HsKAR is NADH dependent, whereas FabG and Oar1p are NADPH dependent |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: HDA mitochondrial proteomics (PMID:24769239) detecting Oar1. Correct; core location. Supporting Evidence: PMID:24769239 quantitative proteomic and phosphoproteomic study of isolated mitochondria |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (Mitochondrion). Correct. Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0005739 mitochondrion | IMP PMID:9388293 Two genes of the putative mitochondrial fatty acid synthase ... | ACCEPT | Summary: IMP (Schneider et al. 1997): oar1 disruption gives respiratory deficiency, placing Oar1 in the mitochondrial FAS. Consistent with proteomic localisation. Supporting Evidence: PMID:9388293 We disrupted these two genes which in both cases led to a respiratory deficient phenotype PMID:9388293 They are presumed to be part of a type-II mitochondrial fatty acid synthase |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: RCA (is_active_in) from YeastPathways FASYN-ELONG2-PWY (fatty acid elongation (saturated, ACP-bound)) placing Oar1 in the cytosolic FAS pathway. Oar1 is a mitochondrial mtFAS enzyme; the cytosolic ketoreductase step is catalysed by Fas2. Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion PMID:9388293 They are presumed to be part of a type-II mitochondrial fatty acid synthase PMID:19571038 they rescue the respiratory deficiency and restore the lipoic acid content of oar1Delta cells |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: RCA (is_active_in) from YeastPathways PWY-5971-1 (myristate biosynthesis) placing Oar1 in the cytosolic FAS pathway. Oar1 is a mitochondrial mtFAS enzyme; the cytosolic ketoreductase step is catalysed by Fas2. Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion PMID:9388293 They are presumed to be part of a type-II mitochondrial fatty acid synthase PMID:19571038 they rescue the respiratory deficiency and restore the lipoic acid content of oar1Delta cells |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: RCA (is_active_in) from YeastPathways PWY3O-10 (fatty acid biosynthesis, initial steps) placing Oar1 in the cytosolic FAS pathway. Oar1 is a mitochondrial mtFAS enzyme; the cytosolic ketoreductase step is catalysed by Fas2. Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion PMID:9388293 They are presumed to be part of a type-II mitochondrial fatty acid synthase PMID:19571038 they rescue the respiratory deficiency and restore the lipoic acid content of oar1Delta cells |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: RCA (is_active_in) from YeastPathways PWY3O-355 (stearate biosynthesis III (fungi)) placing Oar1 in the cytosolic FAS pathway. Oar1 is a mitochondrial mtFAS enzyme; the cytosolic ketoreductase step is catalysed by Fas2. Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion PMID:9388293 They are presumed to be part of a type-II mitochondrial fatty acid synthase PMID:19571038 they rescue the respiratory deficiency and restore the lipoic acid content of oar1Delta cells |
| 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 Oar1 in the cytosolic FAS pathway. Oar1 is a mitochondrial mtFAS enzyme; the cytosolic ketoreductase step is catalysed by Fas2. Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion PMID:9388293 They are presumed to be part of a type-II mitochondrial fatty acid synthase PMID:19571038 they rescue the respiratory deficiency and restore the lipoic acid content of oar1Delta cells |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: RCA (is_active_in) from YeastPathways PWY3O-6336 (superpathway of fatty acid biosynthesis, saturated) placing Oar1 in the cytosolic FAS pathway. Oar1 is a mitochondrial mtFAS enzyme; the cytosolic ketoreductase step is catalysed by Fas2. Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion PMID:9388293 They are presumed to be part of a type-II mitochondrial fatty acid synthase PMID:19571038 they rescue the respiratory deficiency and restore the lipoic acid content of oar1Delta cells |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: RCA (is_active_in) from YeastPathways PWY3O-8514 (palmitate biosynthesis) placing Oar1 in the cytosolic FAS pathway. Oar1 is a mitochondrial mtFAS enzyme; the cytosolic ketoreductase step is catalysed by Fas2. Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion PMID:9388293 They are presumed to be part of a type-II mitochondrial fatty acid synthase PMID:19571038 they rescue the respiratory deficiency and restore the lipoic acid content of oar1Delta cells |
| GO:0006631 fatty acid metabolic process | IMP PMID:9388293 Two genes of the putative mitochondrial fatty acid synthase ... | TOO GENERAL | Summary: IMP (Schneider et al. 1997). Correct but less specific than fatty acid biosynthetic process. Reason: Correct but less specific parent of the core BP. Supporting Evidence: PMID:9388293 They are presumed to be part of a type-II mitochondrial fatty acid synthase PMID:9388293 We disrupted these two genes which in both cases led to a respiratory deficient phenotype |
| GO:0006633 fatty acid biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from the mitochondrial KAR node PTN002449501 (human HSD17B8 and CBR4). Oar1 is the yeast counterpart; core BP. Supporting Evidence: PMID:19571038 they rescue the respiratory deficiency and restore the lipoic acid content of oar1Delta cells file:yeast/OAR1/OAR1-uniprot.txt FUNCTION: Involved in biosynthesis of fatty acids in mitochondria. |
| GO:0006633 fatty acid biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: IEA from UniPathway UPA00094 (fatty acid biosynthesis). Correct. Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt FUNCTION: Involved in biosynthesis of fatty acids in mitochondria. |
| GO:0006633 fatty acid biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY-5971-1 (myristate biosynthesis). BP correct in essence (Oar1 acts in mitochondrial rather than cytosolic FAS). Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt FUNCTION: Involved in biosynthesis of fatty acids in mitochondria. PMID:9388293 They are presumed to be part of a type-II mitochondrial fatty acid synthase |
| GO:0006633 fatty acid biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-10 (fatty acid biosynthesis, initial steps). BP correct in essence (Oar1 acts in mitochondrial rather than cytosolic FAS). Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt FUNCTION: Involved in biosynthesis of fatty acids in mitochondria. PMID:9388293 They are presumed to be part of a type-II mitochondrial fatty acid synthase |
| GO:0006633 fatty acid biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-355 (stearate biosynthesis III (fungi)). BP correct in essence (Oar1 acts in mitochondrial rather than cytosolic FAS). Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt FUNCTION: Involved in biosynthesis of fatty acids in mitochondria. PMID:9388293 They are presumed to be part of a type-II mitochondrial fatty acid synthase |
| 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). BP correct in essence (Oar1 acts in mitochondrial rather than cytosolic FAS). Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt FUNCTION: Involved in biosynthesis of fatty acids in mitochondria. PMID:9388293 They are presumed to be part of a type-II mitochondrial fatty acid synthase |
| GO:0006633 fatty acid biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-8514 (palmitate biosynthesis). BP correct in essence (Oar1 acts in mitochondrial rather than cytosolic FAS). Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt FUNCTION: Involved in biosynthesis of fatty acids in mitochondria. PMID:9388293 They are presumed to be part of a type-II mitochondrial fatty acid synthase |
| GO:0009060 aerobic respiration | IMP PMID:9388293 Two genes of the putative mitochondrial fatty acid synthase ... | MARK AS OVER ANNOTATED | Summary: IMP (Schneider et al. 1997): oar1 null is respiratory deficient. This is a downstream consequence of losing mtFAS products (octanoyl-ACP for lipoylation of PDH/KGDH and acyl chains needed for respiratory complexes); Oar1 does not perform a step of respiration. Reason: Indirect phenotype; Oar1 does not perform any step of aerobic respiration. Supporting Evidence: PMID:9388293 We disrupted these two genes which in both cases led to a respiratory deficient phenotype PMID:19571038 Mitochondrial fatty acid synthesis (FAS) generates the octanoyl-group that is required for the synthesis of lipoic acid |
| GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor | IBA GO_REF:0000033 | TOO GENERAL | Summary: IBA from SDR node PTN002449287. Correct parent of 3-oxoacyl-ACP reductase (NADPH) activity but uninformative. Reason: Uninformative parent of the core MF. Supporting Evidence: file:yeast/OAR1/OAR1-uniprot.txt Reaction=a (3R)-hydroxyacyl-[ACP] + NADP(+) = a 3-oxoacyl-[ACP] + NADPH |
| 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 FAS/elongation pathway. Oar1 reduces 3-oxoacyl-ACP in each mitochondrial FAS cycle (mainly up to the octanoyl lipoate precursor), captured by fatty acid biosynthetic process; it has no role in the cytosolic elongation/stearate pathway from which this term was inferred. Reason: Inherited from a cytosolic pathway; mtFAS cycles are covered by fatty acid biosynthetic process. Supporting Evidence: PMID:19571038 they rescue the respiratory deficiency and restore the lipoic acid content of oar1Delta cells PMID:19571038 Mitochondrial fatty acid synthesis (FAS) generates the octanoyl-group that is required for the synthesis of lipoic acid |
| GO:0030497 fatty acid elongation | RCA GO_REF:0000123 | MARK AS OVER ANNOTATED | Summary: RCA from YeastPathways FASYN-ELONG2-PWY (fatty acid elongation (saturated, ACP-bound)), a cytosolic FAS/elongation pathway. Oar1 reduces 3-oxoacyl-ACP in each mitochondrial FAS cycle (mainly up to the octanoyl lipoate precursor), captured by fatty acid biosynthetic process; it has no role in the cytosolic elongation/stearate pathway from which this term was inferred. Reason: Inherited from a cytosolic pathway; mtFAS cycles are covered by fatty acid biosynthetic process. Supporting Evidence: PMID:19571038 they rescue the respiratory deficiency and restore the lipoic acid content of oar1Delta cells PMID:19571038 Mitochondrial fatty acid synthesis (FAS) generates the octanoyl-group that is required for the synthesis of lipoic acid |
| GO:0048038 quinone binding | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA (quinone binding) from node PTN002449501, sourced from human CBR4 (Q8N4T8), which has an in vitro quinone reductase activity. In vivo CBR4 functions with HSD17B8 as the mitochondrial KAR, and no quinone binding has been shown for Oar1, an NADPH-dependent 3-oxoacyl-ACP reductase. The inherited term reflects a substrate promiscuity of one source rather than the conserved function of the clade. Reason: No evidence for quinone binding by Oar1; propagated from a promiscuous activity of CBR4. Propagation Review Root cause: PROPAGATION BAD Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN002449501 Β· PTN002449501 SUPPORTS SOURCE BUT NOT TARGET Quinone binding/reduction is an in vitro side activity of human CBR4; the conserved clade function is 3-oxoacyl-ACP reduction in mtFAS. Supporting Evidence: PMID:19571038 although HsKAR is NADH dependent, whereas FabG and Oar1p are NADPH dependent file:yeast/OAR1/OAR1-uniprot.txt Reaction=a (3R)-hydroxyacyl-[ACP] + NADP(+) = a 3-oxoacyl-[ACP] + NADPH |
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Experiment: Kinetic characterisation of purified Oar1 with 3-oxoacyl-ACP substrates of varying chain length using yeast holo-Acp1.
Mitochondrial 3-oxoacyl-[acyl-carrier-protein] reductase; may comprise a type II mitochondrial fatty acid synthase along with Mct1p; human homolog CBR4 complements yeast null mutant
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