ABAT

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of mitochondrial localization. ABAT is a mitochondrial matrix enzyme with an N-terminal mitochondrial transit peptide (residues 1-28) and confirmed matrix activity. Correct but general; the more specific mitochondrial matrix term is also annotated. Reason: Consistent with the UniProt SUBCELLULAR LOCATION (Mitochondrion matrix) and the transit peptide feature; well supported by orthology across the family. Supporting Evidence: file:human/ABAT/ABAT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix.
GO:0009450 GABA catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic assignment of GABA catabolic process. This is the core biological process of ABAT: it catalyzes the first step of GABA degradation (the GABA shunt). Reason: Directly supported by the enzyme's characterized activity (GABA + 2-oxoglutarate -> succinate semialdehyde + L-glutamate) and by the disease phenotype (GABATD is described as an inborn error of GABA degradation). This is a core function. Supporting Evidence: PMID:10407778 an inborn error of GABA degradation
GO:0030170 pyridoxal phosphate binding	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic assignment of PLP binding. ABAT is a PLP-dependent class-III aminotransferase; PLP is covalently bound at Lys357 and is essential for catalysis. Reason: Well supported experimentally in human (Lys357 mutants lose PLP-dependent absorption bands and activity) and conserved across the family. Core cofactor function. Supporting Evidence: PMID:15650327 is involved in binding PLP at the active site
GO:0005759 mitochondrial matrix	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment of mitochondrial matrix localization, matching the experimentally/TAS-supported matrix localization. Reason: Consistent with UniProt (Mitochondrion matrix) and Reactome, which state the reaction takes place in the mitochondrial matrix. This is the most specific correct localization. Supporting Evidence: file:human/ABAT/ABAT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix.
GO:0030170 pyridoxal phosphate binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO electronic assignment of PLP binding from the Aminotran_3 (IPR005814) signature. Correct and redundant with the experimental IDA and IBA annotations. Reason: ABAT is a bona fide PLP-dependent aminotransferase; the InterPro mapping is accurate. Supporting Evidence: PMID:15650327 is involved in binding PLP at the active site
GO:0034386 4-aminobutyrate:2-oxoglutarate transaminase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment of the core molecular function (EC 2.6.1.19, RHEA:23352), matching the experimentally demonstrated activity. Reason: This is the primary, experimentally verified catalytic activity of ABAT. Core molecular function. Supporting Evidence: file:human/ABAT/ABAT-uniprot.txt L-glutamate; Xref=Rhea:RHEA:23352
GO:0047298 (S)-3-amino-2-methylpropionate:2-oxoglutarate transaminase activity	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Electronic assignment of the second transaminase activity (EC 2.6.1.22, RHEA:13993): transamination of (S)-3-amino-2-methylpropanoate (L-beta-aminoisobutyrate), linking ABAT to pyrimidine/thymine catabolism. Reason: A genuine secondary activity of ABAT (an AltName of the protein is "(S)-3-amino-2-methylpropionate transaminase"). In human this is a by-similarity / EC-mapped activity rather than the physiological core function (GABA degradation), so it is retained but marked non-core. Supporting Evidence: file:human/ABAT/ABAT-uniprot.txt (S)-3-amino-2-methylpropanoate + 2-oxoglutarate = 2-methyl-3- file:human/ABAT/ABAT-uniprot.txt AltName: Full=(S)-3-amino-2-methylpropionate transaminase
GO:0001666 response to hypoxia	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Automatic transfer (Ensembl Compara, ECO:0000265) of a rat-ortholog phenotype annotation. This is a downstream physiological/environmental-response phenotype, not a molecular function or direct biological role of the human protein. Reason: Transferred from the rodent ortholog (UniProtKB:P50554); "response to hypoxia" is an indirect physiological consequence rather than a demonstrated role of human ABAT. Retained (per policy on plausible orthology transfer) but flagged as over-annotation.
GO:0006540 GABA shunt	IEA GO_REF:0000107	ACCEPT	Summary: Automatic ortholog transfer of GABA shunt involvement. This is genuinely correct for ABAT and is independently supported by the experimental IDA annotation below. Reason: The GABA shunt (GABA -> succinate semialdehyde -> succinate) is ABAT's core pathway; the ortholog transfer is accurate. Supporting Evidence: PMID:15528998 converts the major inhibitory neurotransmitter GABA to succinic
GO:0007620 copulation	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Automatic transfer of a rodent-ortholog behavioural phenotype. Not a molecular function or direct biological role of the human enzyme. Reason: Behavioural phenotype transferred from the rodent ortholog; too indirect to represent human ABAT function.
GO:0007626 locomotory behavior	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Automatic transfer of a rodent-ortholog behavioural phenotype (GABAergic signalling affects locomotion). Downstream consequence of GABA metabolism, not a molecular function of the protein. Reason: Behavioural phenotype transferred from the rodent ortholog; over-annotation relative to the enzyme's direct role.
GO:0009410 response to xenobiotic stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Automatic transfer of a rodent-ortholog environmental-response phenotype. Not a direct function of human ABAT. Reason: Environmental-response phenotype transferred from the rodent ortholog; too indirect to represent human ABAT function.
GO:0010039 response to iron ion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Automatic transfer of a rodent-ortholog response phenotype. ABAT does bind a [2Fe-2S] cluster, but "response to iron ion" is a physiological response process, not the cofactor-binding molecular function, and is transferred by orthology. Reason: Physiological-response phenotype transferred from the rodent ortholog; too indirect to represent human ABAT function.
GO:0014053 negative regulation of gamma-aminobutyric acid secretion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Automatic ortholog transfer. Because ABAT degrades GABA it can lower GABA pools, but "regulation of GABA secretion" is a downstream regulatory-process abstraction rather than the enzyme's direct catalytic function. Reason: Indirect regulatory phenotype transferred from the rodent ortholog; the direct role is captured by GABA catabolic process / GABA shunt.
GO:0021549 cerebellum development	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Automatic transfer of a rodent-ortholog developmental phenotype. Not a molecular function or direct role of the human enzyme. Reason: Developmental phenotype transferred from the rodent ortholog; over-annotation relative to the enzyme's direct GABA-catabolic role.
GO:0031652 positive regulation of heat generation	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Automatic transfer of a rodent-ortholog physiological phenotype. Too indirect to represent human ABAT function. Reason: Physiological phenotype transferred from the rodent ortholog; over-annotation.
GO:0032024 positive regulation of insulin secretion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Automatic ortholog transfer. GABA signalling in pancreatic islets can modulate insulin secretion, but this is a downstream tissue-level phenotype, not a molecular function of the enzyme. Reason: Tissue-level regulatory phenotype transferred from the rodent ortholog; too indirect to represent human ABAT function.
GO:0033602 negative regulation of dopamine secretion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Automatic transfer of a rodent-ortholog neurotransmission phenotype. Downstream consequence of GABA signalling, not a direct function of the enzyme. Reason: Indirect neurotransmission phenotype transferred from the rodent ortholog; over-annotation.
GO:0035094 response to nicotine	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Automatic transfer of a rodent-ortholog pharmacological-response phenotype. Not a direct function of human ABAT. Reason: Pharmacological-response phenotype transferred from the rodent ortholog; too indirect.
GO:0035640 exploration behavior	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Automatic transfer of a rodent-ortholog behavioural phenotype. Not a molecular function or direct role of the human enzyme. Reason: Behavioural phenotype transferred from the rodent ortholog; over-annotation.
GO:0042220 response to cocaine	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Automatic transfer of a rodent-ortholog pharmacological-response phenotype. Too indirect to represent human ABAT function. Reason: Pharmacological-response phenotype transferred from the rodent ortholog; over-annotation.
GO:0045471 response to ethanol	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Automatic transfer of a rodent-ortholog response phenotype. Not a direct function of human ABAT. Reason: Response phenotype transferred from the rodent ortholog; over-annotation.
GO:0045776 negative regulation of blood pressure	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Automatic transfer of a rodent-ortholog physiological phenotype. Too indirect to represent human ABAT function. Reason: Physiological phenotype transferred from the rodent ortholog; over-annotation.
GO:0045964 positive regulation of dopamine metabolic process	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Automatic transfer of a rodent-ortholog metabolic-regulation phenotype. Downstream of GABA signalling, not a direct function of the enzyme. Reason: Indirect regulatory phenotype transferred from the rodent ortholog; over-annotation.
GO:0050877 nervous system process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Automatic transfer (from a mouse ortholog) of a high-level nervous-system-process term. ABAT terminates GABAergic inhibitory signalling by degrading GABA, so a neural-process role is biologically reasonable but non-core and very general. Reason: Plausible given ABAT's role in GABA neurotransmitter turnover, but a broad, indirect BP term rather than the enzyme's direct catalytic function; keep as non-core.
GO:0070474 positive regulation of uterine smooth muscle contraction	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Automatic transfer of a rodent-ortholog physiological phenotype. Too indirect to represent human ABAT function. Reason: Physiological phenotype transferred from the rodent ortholog; over-annotation.
GO:0097151 positive regulation of inhibitory postsynaptic potential	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Automatic ortholog transfer. GABA is the major inhibitory neurotransmitter and ABAT controls its turnover, but IPSP regulation is a downstream neurophysiological consequence, not a molecular function of the enzyme. Reason: Indirect neurophysiological phenotype transferred from the rodent ortholog; over-annotation relative to the enzyme's direct GABA-catabolic role.
GO:1902722 positive regulation of prolactin secretion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Automatic transfer of a rodent-ortholog endocrine phenotype. Too indirect to represent human ABAT function. Reason: Endocrine-regulation phenotype transferred from the rodent ortholog; over-annotation.
GO:1904450 positive regulation of aspartate secretion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Automatic transfer of a rodent-ortholog neurotransmitter-secretion phenotype. Too indirect to represent human ABAT function. Reason: Indirect secretion phenotype transferred from the rodent ortholog; over-annotation.
GO:0006540 GABA shunt	IDA PMID:15528998 Cysteine-321 of human brain GABA transaminase is involved in...	ACCEPT	Summary: Direct experimental (IDA) annotation of GABA shunt involvement. Yoon et al. characterized human brain GABA-T as a key homodimeric enzyme of the GABA shunt that converts GABA to succinic semialdehyde. Reason: Directly supported experimental annotation for a core pathway of ABAT. Supporting Evidence: PMID:15528998 converts the major inhibitory neurotransmitter GABA to succinic
GO:0005739 mitochondrion	IDA GO_REF:0000052	ACCEPT	Summary: Immunofluorescence-based (HPA) localization to mitochondrion. Consistent with the matrix localization established biochemically and by Reactome. Reason: Correct localization; general term (the specific matrix term is also annotated). Supporting Evidence: file:human/ABAT/ABAT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix.
GO:0034386 4-aminobutyrate:2-oxoglutarate transaminase activity	IDA PMID:15528998 Cysteine-321 of human brain GABA transaminase is involved in...	ACCEPT	Summary: Direct experimental (IDA) annotation of the core transaminase activity, with contributes_to reflecting that the active enzyme is a homodimer. Yoon et al. showed wild-type enzyme is active while active-site/dimerization mutants are inactive. Reason: Core molecular function, experimentally demonstrated; the contributes_to qualifier is appropriate for the obligate homodimer. Supporting Evidence: PMID:15528998 converts the major inhibitory neurotransmitter GABA to succinic PMID:15528998 the Cys321 residue is essential for the catalytic function of GABA-T
GO:0050877 nervous system process	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity (ISS, from mouse ortholog) assignment of a high-level nervous-system-process term. Biologically reasonable given ABAT's role in GABAergic neurotransmitter turnover, but broad and non-core. Reason: Plausible but indirect and very general; keep as a non-core biological role.
GO:0047298 (S)-3-amino-2-methylpropionate:2-oxoglutarate transaminase activity	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity (ISS, from rat P50554) assignment of the second transaminase activity (EC 2.6.1.22). Reflects ABAT's ability to transaminate L-beta-aminoisobutyrate, an AltName activity of the protein. Reason: A genuine secondary activity (by similarity in human) rather than the physiological core function; retained as non-core. Supporting Evidence: file:human/ABAT/ABAT-uniprot.txt AltName: Full=(S)-3-amino-2-methylpropionate transaminase
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: High-throughput (HTP) identification of ABAT as a member of the high-confidence human mitochondrial proteome (MitoCoP). Consistent with all other localization evidence. Reason: Corroborates mitochondrial localization; general term, redundant with the matrix annotations. Supporting Evidence: PMID:34800366 mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)
GO:0034386 4-aminobutyrate:2-oxoglutarate transaminase activity	IDA PMID:10407778 4-Aminobutyrate aminotransferase (GABA-transaminase) deficie...	ACCEPT	Summary: Direct experimental (IDA) annotation of the core transaminase activity, from Medina-Kauwe et al., who expressed recombinant human GABA-T and its GABATD R220K variant and measured enzymatic activity (variant Vmax reduced to 25% of wild-type). Reason: Core molecular function, experimentally demonstrated for the human enzyme. Supporting Evidence: PMID:10407778 Vmax was reduced to 25% of wild-type activity
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-916855	ACCEPT	Summary: Traceable-author-statement (Reactome) localization to the mitochondrial matrix, where the GABA -> succinate semialdehyde reaction occurs. This is the most specific correct localization for ABAT. Reason: Well supported; matches UniProt (Mitochondrion matrix) and the Reactome reaction description. Supporting Evidence: file:human/ABAT/ABAT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix.
GO:0005739 mitochondrion	IDA GO_REF:0000054	ACCEPT	Summary: Localization of an expressed fusion protein (LIFEdb) to mitochondrion. Consistent with all other localization evidence. Reason: Correct localization; general term, redundant with the matrix annotations. Supporting Evidence: file:human/ABAT/ABAT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix.
GO:0005739 mitochondrion	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity (ISS, from chicken Q9BGI0) assignment of mitochondrial localization. Consistent with all other localization evidence. Reason: Correct localization; general term, redundant with the more specific matrix annotations. Supporting Evidence: file:human/ABAT/ABAT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix.
GO:0032144 4-aminobutyrate transaminase complex	IDA PMID:15528998 Cysteine-321 of human brain GABA transaminase is involved in...	ACCEPT	Summary: Direct experimental (IDA) annotation that ABAT is part of the 4-aminobutyrate transaminase complex. The active enzyme is a disulfide-linked homodimer; Yoon et al. showed wild-type GABA-T exists as an oligomeric ~100 kDa species linked by a Cys321 disulfide between monomers. Reason: Directly supported: ABAT is the obligate homodimeric GABA-transaminase complex. Supporting Evidence: PMID:15528998 involved in the formation of a disulfide link between two monomers
GO:0032145 succinate-semialdehyde dehydrogenase binding	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity (ISS, from pig P80147) assignment of succinate-semialdehyde dehydrogenase (SSADH) binding. GABA-T and SSADH act sequentially in the GABA shunt (GABA -> succinate semialdehyde -> succinate) and are reported to physically associate. Reason: A specific, named binding partner (not generic "protein binding"), consistent with the coupled GABA-shunt reactions; retained as a non-core supporting molecular function based on orthology.
GO:0030170 pyridoxal phosphate binding	IDA PMID:15650327 Site-directed mutagenesis of human brain GABA transaminase: ...	ACCEPT	Summary: Direct experimental (IDA) annotation of PLP binding. Kim et al. showed Lys357 is essential for catalysis and for binding PLP at the active site; K357 mutants lacked the characteristic PLP absorption bands (330/415 nm) and activity. Reason: Core cofactor-binding function, experimentally demonstrated for the human enzyme. Supporting Evidence: PMID:15650327 is involved in binding PLP at the active site

Gene Description

Existing Annotations Review

Core Functions

PLP-dependent 4-aminobutyrate:2-oxoglutarate transaminase (GABA transaminase, EC 2.6.1.19) catalyzing the first step of GABA degradation in the mitochondrial matrix: GABA + 2-oxoglutarate -> succinate semialdehyde + L-glutamate.

Pyridoxal-5'-phosphate cofactor binding at the active site (covalent Schiff base at Lys357), required for the transaminase catalytic mechanism.

References

📚 Additional Documentation

Notes

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