OAC1

UniProt ID: P32332
Organism: Saccharomyces cerevisiae S288C
Review Status: COMPLETE
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Gene Description

OAC1 (YKL120W) encodes the mitochondrial oxaloacetate carrier, a member of the mitochondrial carrier (SLC25) family located in the inner mitochondrial membrane. Reconstituted Oac1 transports oxaloacetate, malonate, sulfate and thiosulfate by uniport and by exchange, and also transports alpha- and beta-isopropylmalate with high affinity. In vivo, Oac1 exports alpha-isopropylmalate (the first committed intermediate of leucine biosynthesis, made by mitochondrial Leu4) to the cytosol, probably in exchange for oxaloacetate; oac1 leu4 double mutants are leucine auxotrophs on fermentable carbon sources. It was originally proposed to import cytosolic oxaloacetate made by pyruvate carboxylase into mitochondria.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005739 mitochondrion
HDA
PMID:16823961
Toward the complete yeast mitochondrial proteome: multidimen...
ACCEPT
Summary: HDA from a mitochondrial proteomics survey (Reinders et al. 2006) detecting Oac1 in purified mitochondria. Correct but less specific than the inner-membrane localization established for this carrier.
Supporting Evidence:
PMID:16823961
Toward the complete yeast mitochondrial proteome
PMID:10428783
In S. cerevisiae, OAC is in inner mitochondrial membranes
GO:0005739 mitochondrion
HDA
PMID:24769239
Quantitative variations of the mitochondrial proteome and ph...
ACCEPT
Summary: HDA from quantitative mitochondrial proteomics (Renvoise et al. 2014) detecting Oac1 in mitochondria. Correct; inner membrane is the more precise location.
Supporting Evidence:
PMID:24769239
Quantitative variations of the mitochondrial proteome and phosphoproteome
PMID:10428783
In S. cerevisiae, OAC is in inner mitochondrial membranes
GO:0005743 mitochondrial inner membrane
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from the mitochondrial carrier PTN002515516 node. Oac1 is a canonical SLC25 carrier and is experimentally located in the inner membrane, so the inherited location is correct for this protein.
Supporting Evidence:
PMID:10428783
In S. cerevisiae, OAC is in inner mitochondrial membranes
GO:0005743 mitochondrial inner membrane
IDA
PMID:10428783
Identification of the yeast mitochondrial transporter for ox...
ACCEPT
Summary: IDA (Palmieri et al. 1999): Oac1 was localized to inner mitochondrial membranes. This is the site where it carries out oxaloacetate/sulfate/alpha-isopropylmalate transport.
Supporting Evidence:
PMID:10428783
In S. cerevisiae, OAC is in inner mitochondrial membranes
GO:0005743 mitochondrial inner membrane
IEA
GO_REF:0000044
ACCEPT
Summary: IEA from UniProt subcellular location (inner membrane, multi-pass) mapped to GO. Consistent with the IDA evidence.
Supporting Evidence:
PMID:10428783
In S. cerevisiae, OAC is in inner mitochondrial membranes
GO:0015116 sulfate transmembrane transporter activity
IDA
PMID:10428783
Identification of the yeast mitochondrial transporter for ox...
ACCEPT
Summary: IDA: reconstituted Oac1 transports sulfate (and thiosulfate), and oac1 deletion reduces mitochondrial sulfate transport. Sulfate is a genuine substrate and is used as counter-anion in the exchange assays, though its physiological significance is less clear than that of alpha-IPM/oxaloacetate.
Supporting Evidence:
PMID:10428783
demonstration that the proteoliposomes transport malonate, oxaloacetate, sulfate, and thiosulfate
PMID:10428783
deletion of its gene greatly reduces transport of oxaloacetate sulfate, thiosulfate, and malonate
GO:0015131 oxaloacetate transmembrane transporter activity
IDA
PMID:10428783
Identification of the yeast mitochondrial transporter for ox...
ACCEPT
Summary: IDA: reconstituted Oac1 transports oxaloacetate and deletion reduces mitochondrial oxaloacetate transport. This is the defining activity of the carrier and the likely counter-substrate for alpha-IPM export.
Supporting Evidence:
PMID:10428783
demonstration that the proteoliposomes transport malonate, oxaloacetate, sulfate, and thiosulfate
PMID:10428783
deletion of its gene greatly reduces transport of oxaloacetate sulfate, thiosulfate, and malonate
PMID:18682385
Oac1p is important for leucine biosynthesis on fermentable carbon sources catalyzing the export of alpha-IPM, probably in exchange for oxalacetate
GO:0015729 oxaloacetate transport
IDA
PMID:10428783
Identification of the yeast mitochondrial transporter for ox...
ACCEPT
Summary: IDA for oxaloacetate transport (Palmieri et al. 1999). Correct; the transmembrane-specific child (GO:1902356, also present) captures the same process.
Supporting Evidence:
PMID:10428783
demonstration that the proteoliposomes transport malonate, oxaloacetate, sulfate, and thiosulfate
PMID:10428783
The main physiological role of OAC appears to be to use the proton-motive force to take up into mitochondria oxaloacetate produced from pyruvate by cytoplasmic pyruvate carboxylase
GO:0022857 transmembrane transporter activity
IBA
GO_REF:0000033
MARK AS OVER ANNOTATED
Summary: IBA to the root transporter activity term from the mitochondrial carrier family node. Not wrong, but uninformative given experimentally determined, specific substrate activities (oxaloacetate, sulfate, malonate, isopropylmalate) for Oac1.
Reason: Superseded by specific IDA transporter activities for the same protein.
Propagation Review
Root cause: NO FAILURE NON CORE
Failure modes: GRANULARITY MISMATCH
Supporting Evidence:
PMID:18682385
Recombinant and reconstituted mitochondrial oxalacetate carrier (Oac1p) efficiently transported alpha-IPM in addition to its known substrates oxalacetate, sulfate, and malonate
GO:0034658 isopropylmalate transmembrane transporter activity
IDA
PMID:18682385
alpha-Isopropylmalate, a leucine biosynthesis intermediate i...
ACCEPT
Summary: IDA (Marobbio et al. 2008): recombinant reconstituted Oac1 efficiently transports alpha-IPM (Km 75 uM), and genetics (oac1 leu4 leucine auxotrophy) shows that this export supplies cytosolic leucine synthesis. This is the role Oac1 fills in the branched-chain amino acid biosynthesis pathway.
Supporting Evidence:
PMID:18682385
Recombinant and reconstituted mitochondrial oxalacetate carrier (Oac1p) efficiently transported alpha-IPM in addition to its known substrates oxalacetate, sulfate, and malonate
PMID:18682385
the double mutant DeltaOAC1DeltaLEU4 did not grow at all on fermentable substrates in the absence of leucine
PMID:18682385
Oac1p is important for leucine biosynthesis on fermentable carbon sources catalyzing the export of alpha-IPM, probably in exchange for oxalacetate
GO:0034659 isopropylmalate transport
IDA
PMID:18682385
alpha-Isopropylmalate, a leucine biosynthesis intermediate i...
ACCEPT
Summary: IDA: Oac1 transports alpha-IPM in reconstituted liposomes; physiologically it exports alpha-IPM from the matrix to the cytosol.
Supporting Evidence:
PMID:18682385
Recombinant and reconstituted mitochondrial oxalacetate carrier (Oac1p) efficiently transported alpha-IPM in addition to its known substrates oxalacetate, sulfate, and malonate
PMID:18682385
Oac1p is important for leucine biosynthesis on fermentable carbon sources catalyzing the export of alpha-IPM, probably in exchange for oxalacetate
GO:0055085 transmembrane transport
IEA
GO_REF:0000002
TOO GENERAL
Summary: IEA from InterPro IPR002067 (mitochondrial carrier) to transmembrane transport. Correct but generic; specific transport processes are annotated separately.
Supporting Evidence:
file:yeast/OAC1/OAC1-uniprot.txt
Antiporter that exchanges dicarboxylates and sulfur oxoanions
GO:1901239 malonate(1-) transmembrane transporter activity
IDA
PMID:10428783
Identification of the yeast mitochondrial transporter for ox...
ACCEPT
Summary: IDA: reconstituted Oac1 transports malonate. Valid substrate activity, of uncertain physiological importance.
Supporting Evidence:
PMID:10428783
demonstration that the proteoliposomes transport malonate, oxaloacetate, sulfate, and thiosulfate
PMID:10428783
deletion of its gene greatly reduces transport of oxaloacetate sulfate, thiosulfate, and malonate
GO:1901553 malonic acid transmembrane transport
IEA
GO_REF:0000108
ACCEPT
Summary: IEA by inter-ontology inference from the malonate transporter activity IDA. Consistent with that annotation.
Supporting Evidence:
PMID:10428783
demonstration that the proteoliposomes transport malonate, oxaloacetate, sulfate, and thiosulfate
GO:1902356 oxaloacetate(2-) transmembrane transport
IEA
GO_REF:0000108
ACCEPT
Summary: IEA by inter-ontology inference from the oxaloacetate transporter activity IDA. Consistent with the experimental data.
Supporting Evidence:
PMID:10428783
demonstration that the proteoliposomes transport malonate, oxaloacetate, sulfate, and thiosulfate
PMID:10428783
deletion of its gene greatly reduces transport of oxaloacetate sulfate, thiosulfate, and malonate
GO:1902358 sulfate transmembrane transport
IDA
PMID:10428783
Identification of the yeast mitochondrial transporter for ox...
ACCEPT
Summary: IDA: Oac1 mediates sulfate uniport/exchange across reconstituted membranes and deletion reduces mitochondrial sulfate transport.
Supporting Evidence:
PMID:10428783
demonstration that the proteoliposomes transport malonate, oxaloacetate, sulfate, and thiosulfate
PMID:10428783
deletion of its gene greatly reduces transport of oxaloacetate sulfate, thiosulfate, and malonate

Core Functions

Mitochondrial inner-membrane carrier that exports alpha-isopropylmalate from the matrix to the cytosol, probably in exchange for oxaloacetate, supplying the cytosolic steps of leucine biosynthesis.

Supporting Evidence:
  • PMID:18682385
    Recombinant and reconstituted mitochondrial oxalacetate carrier (Oac1p) efficiently transported alpha-IPM in addition to its known substrates oxalacetate, sulfate, and malonate
  • PMID:18682385
    Oac1p is important for leucine biosynthesis on fermentable carbon sources catalyzing the export of alpha-IPM, probably in exchange for oxalacetate
  • PMID:18682385
    the double mutant DeltaOAC1DeltaLEU4 did not grow at all on fermentable substrates in the absence of leucine

Oxaloacetate (and sulfate/malonate) transport across the inner membrane by uniport or exchange.

Supporting Evidence:
  • PMID:10428783
    demonstration that the proteoliposomes transport malonate, oxaloacetate, sulfate, and thiosulfate
  • PMID:10428783
    deletion of its gene greatly reduces transport of oxaloacetate sulfate, thiosulfate, and malonate

References

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Suggested Questions for Experts

Q: What is the in vivo counter-substrate for alpha-isopropylmalate export by Oac1 (oxaloacetate, sulfate or another anion), and does Oac1 still import oxaloacetate under respiratory conditions?

Suggested Experiments

Experiment: Measure matrix and cytosolic alpha-IPM and oxaloacetate pools in oac1, leu4 and oac1 leu4 strains by compartment-resolved metabolomics on glucose and on non-fermentable carbon sources.

Deep Research

SGD

(OAC1-deep-research-sgd.md)
SGD gene description for OAC1 (yeast) SGD

SGD gene description for OAC1 (yeast)

Mitochondrial inner membrane transporter; transports oxaloacetate, sulfate, thiosulfate, and isopropylmalate; member of the mitochondrial carrier family

πŸ“š Additional Documentation

Notes

(OAC1-notes.md)

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