OAR1

UniProt ID: P35731
Organism: Saccharomyces cerevisiae S288C
Review Status: COMPLETE
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Gene Description

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).

Existing Annotations Review

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

Core Functions

Mitochondrial NADPH-dependent 3-oxoacyl-ACP reductase catalysing the first reduction of each type II mitochondrial fatty acid synthesis cycle.

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
  • PMID:19571038
    they rescue the respiratory deficiency and restore the lipoic acid content of oar1Delta cells
  • PMID:9388293
    They are presumed to be part of a type-II mitochondrial fatty acid synthase

References

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Suggested Questions for Experts

Q: Does yeast Oar1 act as a homotetramer, unlike the human HSD17B8/CBR4 heterotetramer, and what is its acyl-chain-length preference?

Suggested Experiments

Experiment: Kinetic characterisation of purified Oar1 with 3-oxoacyl-ACP substrates of varying chain length using yeast holo-Acp1.

Deep Research

SGD

(OAR1-deep-research-sgd.md)
SGD gene description for OAR1 (yeast) SGD

SGD gene description for OAR1 (yeast)

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

πŸ“š Additional Documentation

Notes

(OAR1-notes.md)

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