Ornithine aminotransferase (OAT; EC 2.6.1.13) is a nuclear-encoded, mitochondrial matrix, pyridoxal 5'-phosphate-dependent enzyme that reversibly transfers the delta-amino group of L-ornithine to 2-oxoglutarate, forming L-glutamate 5-semialdehyde and L-glutamate. The semialdehyde interconverts spontaneously with pyrroline-5-carboxylate, linking ornithine and arginine degradation to glutamate and proline metabolism. Its functional catalytic unit is a homodimer; recombinant human protein exhibits a tetramer–dimer equilibrium, while crystal structures also show hexameric assemblies. Net reaction direction depends on tissue, developmental stage and substrate supply. Ornithine degradation is prominent in many adult tissues, whereas intestinal ornithine synthesis supports citrulline and arginine production, particularly during early development. Biallelic loss of function causes gyrate atrophy of the choroid and retina, usually with hyperornithinemia after infancy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004587 L-ornithine transaminase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA/PAN-GO) assignment of the core ornithine aminotransferase molecular function. This is the correct catalytic activity for OAT (EC 2.6.1.13) and is corroborated by direct experimental evidence (IMP in PMID:1737786 and PMID:23076989), the cofactor structure, and the UniProt CATALYTIC ACTIVITY block. Reason: Phylogenetic (IBA/PAN-GO) assignment of the core ornithine aminotransferase molecular function. This is the correct catalytic activity for OAT (EC 2.6.1.13) and is corroborated by direct experimental evidence (IMP in PMID:1737786 and PMID:23076989), the cofactor structure, and the UniProt CATALYTIC ACTIVITY block. Supporting Evidence: file:human/OAT/OAT-uniprot.txt Catalyzes the reversible interconversion of L-ornithine and |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrial residence is a supported core localization. Reason: The human cloning and precursor-processing studies identify a mitochondrial matrix enzyme (PMID:3456579, PMID:1737786), supporting mitochondrial residence as a core location. Retain the organelle assertion alongside the existing matrix assertion; the original imaging or proteomics assays need not resolve the submitochondrial compartment. The inherited organelle claim agrees with independent target evidence; no ancestral-node placement defect is established or inferred from its breadth. Supporting Evidence: PMID:3456579 a nonabundant mitochondrial matrix enzyme |
| GO:0006527 L-arginine catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: OAT catalyzes the ornithine step of arginase-dependent arginine degradation. Reason: By directly converting arginase-derived ornithine to glutamate semialdehyde and glutamate, OAT executes a catabolic step. Ornithine can have other sources, and reverse flux in intestinal/developmental contexts does not invalidate participation in the forward route. Neither ARG1 nor ARG2 is an obligatory universal upstream partner. Supporting Evidence: PMID:1737786 enzyme which catalyzes the reversible interconversion of ornithine and alpha-ketoglutarate to glutamate semialdehyde and glutamate PMID:28272331 OAT is used to produce Cit from Glu |
| GO:0004587 L-ornithine transaminase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment of the ornithine aminotransferase activity via InterPro/RHEA/EC mapping (IPR010164, RHEA:25160, EC:2.6.1.13). Consistent with the experimentally supported core MF. Accept. Reason: Electronic assignment of the ornithine aminotransferase activity via InterPro/RHEA/EC mapping (IPR010164, RHEA:25160, EC:2.6.1.13). Redundant with, and consistent with, the experimentally supported core MF. Accept. Supporting Evidence: file:human/OAT/OAT-uniprot.txt Catalyzes the reversible interconversion of L-ornithine and |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment (ARBA / UniProtKB-SubCell SL-0170) of mitochondrial matrix localization. Matches the experimentally determined location and is the correct specific compartment. Accept as core location. Reason: Electronic assignment (ARBA / UniProtKB-SubCell SL-0170) of mitochondrial matrix localization. Matches the experimentally determined location and is the correct specific compartment. Accept as core location. Supporting Evidence: file:human/OAT/OAT-uniprot.txt Mitochondrion matrix |
| GO:0008483 transaminase activity | IEA GO_REF:0000117 | MODIFY | Summary: Refine the broad transaminase activity to the established ornithine-specific reaction. Reason: The general activity is true, but human enzyme chemistry supports GO:0004587 already present in this review. This is specificity refinement, not evidence that the parent activity is incorrect. Proposed replacements: L-ornithine transaminase activity Supporting Evidence: PMID:1737786 enzyme which catalyzes the reversible interconversion of ornithine and alpha-ketoglutarate to glutamate semialdehyde and glutamate |
| GO:0030170 pyridoxal phosphate binding | IEA GO_REF:0000002 | ACCEPT | Summary: PLP is the directly observed catalytic cofactor of human OAT. Reason: The human crystal structure (PMID:9514741) identifies the PLP Schiff base and the 2017 biochemical study tests holo/apo forms. The InterPro-based inference is independently supported by this target evidence. Supporting Evidence: PMID:9514741 The cofactor pyridoxal-5'-phosphate is bound through a Schiff base to Lys292 |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Remove the uninformative bare protein-binding term under the current project policy. Reason: The reported OAT–APP interaction from PMID:32814053 is retained as interaction evidence. Generic protein binding does not identify a molecular function, and this assay does not establish a more specific functional role for the interaction. Removal does not dispute that the proteins interacted. Supporting Evidence: file:human/OAT/OAT-uniprot.txt P04181; P05067: APP; NbExp=3; |
| GO:0005739 mitochondrion | IEA GO_REF:0000107 | ACCEPT | Summary: Mitochondrial residence is a supported core localization. Reason: The human cloning and precursor-processing studies identify a mitochondrial matrix enzyme (PMID:3456579, PMID:1737786), supporting mitochondrial residence as a core location. Retain the organelle assertion alongside the existing matrix assertion; the original imaging or proteomics assays need not resolve the submitochondrial compartment. Independent target localization supports the transferred organelle claim without treating the computational row as a new direct experiment. Supporting Evidence: PMID:3456579 a nonabundant mitochondrial matrix enzyme |
| GO:0055129 L-proline biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway mapping (UPA00098) of L-proline biosynthesis. OAT catalyzes step 1/1 of the L-glutamate-5-semialdehyde-from-L-ornithine sub-pathway (the semialdehyde/P5C feeding proline synthesis), so this is a genuine core biological process for the enzyme. Accept. Reason: UniPathway mapping (UPA00098) of L-proline biosynthesis. OAT catalyzes step 1/1 of the L-glutamate-5-semialdehyde-from-L-ornithine sub-pathway (the semialdehyde/P5C feeding proline synthesis), so this is a genuine core biological process for the enzyme. Accept. Supporting Evidence: file:human/OAT/OAT-uniprot.txt L-proline biosynthesis; L-glutamate |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | ACCEPT | Summary: Mitochondrial residence is a supported core localization. Reason: The human cloning and precursor-processing studies identify a mitochondrial matrix enzyme (PMID:3456579, PMID:1737786), supporting mitochondrial residence as a core location. Retain the organelle assertion alongside the existing matrix assertion; the original imaging or proteomics assays need not resolve the submitochondrial compartment. Supporting Evidence: PMID:3456579 a nonabundant mitochondrial matrix enzyme |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: Mitochondrial residence is a supported core localization. Reason: The human cloning and precursor-processing studies identify a mitochondrial matrix enzyme (PMID:3456579, PMID:1737786), supporting mitochondrial residence as a core location. Retain the organelle assertion alongside the existing matrix assertion; the original imaging or proteomics assays need not resolve the submitochondrial compartment. Supporting Evidence: PMID:3456579 a nonabundant mitochondrial matrix enzyme |
| GO:0004587 L-ornithine transaminase activity | IMP PMID:1737786 Ornithine delta-aminotransferase mutations in gyrate atrophy... | ACCEPT | Summary: Experimental (IMP) support for ornithine aminotransferase activity: gyrate-atrophy missense alleles were reproduced by site-directed mutagenesis and expressed in CHO cells, and shown to inactivate the enzyme, demonstrating that OAT carries this catalytic activity. Core molecular function. Accept. Reason: Experimental (IMP) support for ornithine aminotransferase activity: gyrate-atrophy missense alleles were reproduced by site-directed mutagenesis and expressed in CHO cells, and shown to inactivate the enzyme, demonstrating that OAT carries this catalytic activity. Core molecular function. Accept. Supporting Evidence: PMID:1737786 confirms that several of these mutations inactivate ornithine delta-aminotransferase and cause gyrate atrophy |
| GO:0004587 L-ornithine transaminase activity | IMP PMID:23076989 Functional analysis of missense mutations of OAT, causing gy... | ACCEPT | Summary: Experimental (IMP) support for ornithine aminotransferase activity: OAT missense mutants expressed in a yeast strain lacking the OAT ortholog "markedly reduced enzymatic activity", confirming that OAT catalyzes this reaction. Core molecular function. Accept. Reason: Experimental (IMP) support for ornithine aminotransferase activity: OAT missense mutants expressed in a yeast strain lacking the OAT ortholog "markedly reduced enzymatic activity", confirming that OAT catalyzes this reaction. Core molecular function. Accept. Supporting Evidence: PMID:23076989 All mutations markedly reduced enzymatic activity. |
| GO:0005759 mitochondrial matrix | IDA PMID:23076989 Functional analysis of missense mutations of OAT, causing gy... | ACCEPT | Summary: Direct experimental (IDA) determination of mitochondrial-matrix localization from the functional-analysis study of OAT. This is the specific, correct compartment and the core location for the enzyme. Accept. Reason: Direct experimental (IDA) determination of mitochondrial-matrix localization from the functional-analysis study of OAT. This is the specific, correct compartment and the core location for the enzyme. Accept. Supporting Evidence: PMID:3456579 a nonabundant mitochondrial matrix enzyme |
| GO:0042802 identical protein binding | IPI PMID:23076989 Functional analysis of missense mutations of OAT, causing gy... | ACCEPT | Summary: Human OAT self-association forms a functional dimeric catalytic unit. Reason: The original PMID:23076989 describes hexamer assembly defects, but later direct solution/kinetic studies (PMID:28345116) establish tetramer–dimer equilibrium and an active engineered dimer. Retain identical protein binding as a core assembly property without requiring an obligatory active homohexamer or inferring that all oligomeric states are equivalent in cells. Supporting Evidence: PMID:28345116 This finding indicates that the catalytic unit of hOAT is the dimer. PMID:9514741 The active sites of the dimer lie, about 25 A apart, at the subunit and domain interfaces. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-70654 | ACCEPT | Summary: Reactome traceable assignment of mitochondrial-matrix localization (forward reaction: ornithine + alpha-ketoglutarate -> glutamate + glutamate gamma-semialdehyde). Consistent with the experimental location. Accept. Reason: Reactome traceable assignment of mitochondrial-matrix localization (forward reaction: ornithine + alpha-ketoglutarate -> glutamate + glutamate gamma-semialdehyde). Consistent with the experimental location. Accept. Supporting Evidence: PMID:3456579 a nonabundant mitochondrial matrix enzyme |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-70666 | ACCEPT | Summary: Reactome traceable assignment of mitochondrial-matrix localization (reverse reaction: glutamate + glutamate gamma-semialdehyde -> ornithine + alpha-ketoglutarate). Consistent with the experimental location. Accept. Reason: Reactome traceable assignment of mitochondrial-matrix localization (reverse reaction: glutamate + glutamate gamma-semialdehyde -> ornithine + alpha-ketoglutarate). Consistent with the experimental location. Accept. Supporting Evidence: PMID:3456579 a nonabundant mitochondrial matrix enzyme |
| GO:0005759 mitochondrial matrix | NAS PMID:3456579 Molecular cloning of human ornithine aminotransferase mRNA. | ACCEPT | Summary: Non-traceable author statement (cDNA-cloning paper) describing OAT as a mitochondrial matrix enzyme. Consistent with the experimentally supported location, though weaker evidence than the IDA. Accept. Reason: Non-traceable author statement (cDNA-cloning paper) describing OAT as a mitochondrial matrix enzyme. Consistent with the experimentally supported location, though weaker evidence than the IDA. Accept. Supporting Evidence: PMID:3456579 a nonabundant mitochondrial matrix enzyme |
| GO:0004587 L-ornithine transaminase activity | TAS PMID:3456579 Molecular cloning of human ornithine aminotransferase mRNA. | ACCEPT | Summary: Traceable author statement of ornithine aminotransferase activity from the cDNA-cloning paper, which identifies OAT by its enzyme activity (EC 2.6.1.13). Consistent with the core molecular function. Accept. Reason: Traceable author statement of ornithine aminotransferase activity from the cDNA-cloning paper, which identifies OAT by its enzyme activity (EC 2.6.1.13). Consistent with the core molecular function. Accept. Supporting Evidence: PMID:3456579 L-ornithine:2-oxo-acid aminotransferase, EC 2.6.1.13), a nonabundant |
| GO:0007601 visual perception | TAS PMID:2793865 Point mutation affecting processing of the ornithine aminotr... | MARK AS OVER ANNOTATED | Summary: Retinal degeneration establishes disease relevance but does not directly establish execution of visual perception. Reason: PMID:2793865 establishes a mitochondrial OAT processing defect associated with gyrate atrophy. OAT catalyzes amino-acid metabolism; the visual phenotype alone does not identify its participation in a sensory-perception step. This is a bounded concern about process attribution, not a claim that OAT has no retinal role or that visual perception means only phototransduction. Supporting Evidence: PMID:2793865 A generalized deficiency of the mitochondrial enzyme, ornithine aminotransferase (OAT) is the inborn error in gyrate atrophy |
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