OAT

Existing Annotations Review

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. Supporting Evidence: file:human/OAT/OAT-uniprot.txt Catalyzes the reversible interconversion of L-ornithine and
GO:0005739 mitochondrion	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic assignment of mitochondrial localization. Correct but less precise than the experimentally supported mitochondrial matrix (GO:0005759). Keep as a correct general-compartment annotation; the matrix term is the core location. Supporting Evidence: file:human/OAT/OAT-uniprot.txt Mitochondrion matrix
GO:0006527 L-arginine catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic assignment to arginine catabolism. Biologically appropriate: ornithine derived from arginine (via arginase) is catabolized by OAT to glutamate/P5C, so OAT participates in the arginine-to-glutamate/proline catabolic route via ornithine. Accept as a genuine biological process for the enzyme.
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). 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. Supporting Evidence: file:human/OAT/OAT-uniprot.txt Mitochondrion matrix
GO:0008483 transaminase activity	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: ARBA electronic assignment of the general transaminase activity. This is a parent of the specific and experimentally supported ornithine aminotransferase activity (GO:0004587) and adds no information beyond it. Over-annotated (too general). Proposed replacements: L-ornithine transaminase activity
GO:0030170 pyridoxal phosphate binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO electronic assignment of PLP binding (IPR005814). Directly supported by experiment: OAT is a PLP-dependent enzyme with the cofactor covalently bound as a Schiff base at Lys-292 (identified in PMID:3754226) and the crystal structure (PMID:9514741) defines the PLP cofactor. Core cofactor-binding function. Accept. Supporting Evidence: file:human/OAT/OAT-uniprot.txt Name=pyridoxal 5'-phosphate
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from a large-scale neurodegenerative-disease interactome (Y2H) screen, reporting an OAT-APP interaction. Uninformative for OAT's molecular function and the interaction is not an established functional partnership. Retained per policy (do not REMOVE an IPI) but flagged as over-annotated; not used in core functions.
GO:0005739 mitochondrion	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl-Compara orthology transfer of mitochondrial localization (from rat P04182). Correct but less precise than mitochondrial matrix. Keep as a correct general-compartment annotation.
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. Supporting Evidence: file:human/OAT/OAT-uniprot.txt L-proline biosynthesis; L-glutamate
GO:0005739 mitochondrion	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: HPA immunofluorescence localization to mitochondrion. Direct experimental support for mitochondrial localization; correct but less precise than the matrix sub-compartment. Keep as a correct general-compartment annotation.
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	KEEP AS NON CORE	Summary: High-throughput mitochondrial-proteome study assigning OAT to mitochondrion. Consistent with the established localization; less precise than mitochondrial matrix. Keep as a correct general-compartment annotation.
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. 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. 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.
GO:0042802 identical protein binding	IPI PMID:23076989 Functional analysis of missense mutations of OAT, causing gy...	KEEP AS NON CORE	Summary: Self-association annotation reflecting the OAT homohexamer, which is required to form the active enzyme (PMID:23076989 shows mutants that "failed to assemble to form the active OAT hexamer"). Informative for oligomerization but not a distinct catalytic function. Keep as non-core. Supporting Evidence: file:human/OAT/OAT-uniprot.txt Homohexamer.
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.
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.
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. 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. 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: This annotation derives from the disease phenotype: OAT deficiency causes gyrate atrophy of the choroid and retina, which impairs vision. However, OAT is a mitochondrial metabolic enzyme and does not act directly in the visual-perception (phototransduction) process; the retinal degeneration is a downstream consequence of a metabolic defect (hyperornithinemia). This is an over-annotation of the biological process; the retina is affected, but visual perception is not a molecular role of the enzyme.

Core Functions

Pyridoxal-5'-phosphate-dependent ornithine aminotransferase (ornithine delta-aminotransferase, EC 2.6.1.13): reversibly transfers the delta-amino group of L-ornithine to 2-oxoglutarate, forming L-glutamate 5-semialdehyde (which cyclizes to P5C) and L-glutamate, in the mitochondrial matrix. This links the ornithine pool of arginine/urea-cycle metabolism to the glutamate/proline/P5C pool.

Molecular Function:

L-ornithine transaminase activity

Directly Involved In:

L-proline biosynthetic process L-arginine catabolic process

Cellular Locations:

mitochondrial matrix

Supporting Evidence:

file:human/OAT/OAT-uniprot.txt
Catalyzes the reversible interconversion of L-ornithine and
PMID:1737786
ornithine delta-aminotransferase is a nuclear-encoded mitochondrial matrix enzyme which catalyzes the reversible interconversion of ornithine and alpha-ketoglutarate to glutamate semialdehyde and glutamate
PMID:23076989
All mutations markedly reduced enzymatic activity.