id: P80404
gene_symbol: ABAT
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  ABAT is 4-aminobutyrate aminotransferase (GABA transaminase, GABA-T; EC 2.6.1.19), a
  pyridoxal-5'-phosphate (PLP)-dependent, mitochondrial matrix enzyme of the class-III
  aminotransferase family. It catalyzes the first and committed step of GABA degradation
  (the GABA shunt): the reversible transamination of GABA (4-aminobutanoate) with
  2-oxoglutarate to succinate semialdehyde and L-glutamate. The enzyme is a
  disulfide-linked homodimer that carries PLP covalently bound at Lys357 and a [2Fe-2S]
  cluster per dimer, and it also transaminates beta-amino acids such as
  L-beta-aminoisobutyrate ((S)-3-amino-2-methylpropanoate; EC 2.6.1.22, yielding
  methylmalonate semialdehyde), delta-aminovalerate and beta-alanine, linking it to
  pyrimidine/thymine catabolism. ABAT is expressed most highly in liver, pancreas, and
  brain. Loss-of-function variants cause autosomal-recessive GABA-transaminase deficiency
  (GABATD), a severe neonatal/infantile epileptic encephalopathy with elevated GABA.
existing_annotations:
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    reason: >-
      Consistent with the UniProt SUBCELLULAR LOCATION (Mitochondrion matrix) and the
      transit peptide feature; well supported by orthology across the family.
    supported_by:
    - reference_id: file:human/ABAT/ABAT-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Mitochondrion matrix."
- term:
    id: GO:0009450
    label: GABA catabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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).
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:10407778
      supporting_text: "an inborn error of GABA degradation"
- term:
    id: GO:0030170
    label: pyridoxal phosphate binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: >-
      Well supported experimentally in human (Lys357 mutants lose PLP-dependent
      absorption bands and activity) and conserved across the family. Core cofactor
      function.
    supported_by:
    - reference_id: PMID:15650327
      supporting_text: "is involved in binding PLP at the active site"
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: >-
      Electronic assignment of mitochondrial matrix localization, matching the
      experimentally/TAS-supported matrix localization.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/ABAT/ABAT-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Mitochondrion matrix."
- term:
    id: GO:0030170
    label: pyridoxal phosphate binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro2GO electronic assignment of PLP binding from the Aminotran_3
      (IPR005814) signature. Correct and redundant with the experimental IDA and IBA
      annotations.
    action: ACCEPT
    reason: >-
      ABAT is a bona fide PLP-dependent aminotransferase; the InterPro mapping is
      accurate.
    supported_by:
    - reference_id: PMID:15650327
      supporting_text: "is involved in binding PLP at the active site"
- term:
    id: GO:0034386
    label: 4-aminobutyrate:2-oxoglutarate transaminase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Electronic assignment of the core molecular function (EC 2.6.1.19, RHEA:23352),
      matching the experimentally demonstrated activity.
    action: ACCEPT
    reason: >-
      This is the primary, experimentally verified catalytic activity of ABAT. Core
      molecular function.
    supported_by:
    - reference_id: file:human/ABAT/ABAT-uniprot.txt
      supporting_text: "L-glutamate; Xref=Rhea:RHEA:23352"
- term:
    id: GO:0047298
    label: (S)-3-amino-2-methylpropionate:2-oxoglutarate transaminase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/ABAT/ABAT-uniprot.txt
      supporting_text: "(S)-3-amino-2-methylpropanoate + 2-oxoglutarate = 2-methyl-3-"
    - reference_id: file:human/ABAT/ABAT-uniprot.txt
      supporting_text: "AltName: Full=(S)-3-amino-2-methylpropionate transaminase"
- term:
    id: GO:0001666
    label: response to hypoxia
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0006540
    label: GABA shunt
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic ortholog transfer of GABA shunt involvement. This is genuinely correct for
      ABAT and is independently supported by the experimental IDA annotation below.
    action: ACCEPT
    reason: >-
      The GABA shunt (GABA -> succinate semialdehyde -> succinate) is ABAT's core pathway;
      the ortholog transfer is accurate.
    supported_by:
    - reference_id: PMID:15528998
      supporting_text: "converts the major inhibitory neurotransmitter GABA to succinic"
- term:
    id: GO:0007620
    label: copulation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic transfer of a rodent-ortholog behavioural phenotype. Not a molecular
      function or direct biological role of the human enzyme.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Behavioural phenotype transferred from the rodent ortholog; too indirect to
      represent human ABAT function.
- term:
    id: GO:0007626
    label: locomotory behavior
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Behavioural phenotype transferred from the rodent ortholog; over-annotation relative
      to the enzyme's direct role.
- term:
    id: GO:0009410
    label: response to xenobiotic stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic transfer of a rodent-ortholog environmental-response phenotype. Not a
      direct function of human ABAT.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Environmental-response phenotype transferred from the rodent ortholog; too indirect
      to represent human ABAT function.
- term:
    id: GO:0010039
    label: response to iron ion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Physiological-response phenotype transferred from the rodent ortholog; too indirect
      to represent human ABAT function.
- term:
    id: GO:0014053
    label: negative regulation of gamma-aminobutyric acid secretion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Indirect regulatory phenotype transferred from the rodent ortholog; the direct role
      is captured by GABA catabolic process / GABA shunt.
- term:
    id: GO:0021549
    label: cerebellum development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic transfer of a rodent-ortholog developmental phenotype. Not a molecular
      function or direct role of the human enzyme.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Developmental phenotype transferred from the rodent ortholog; over-annotation
      relative to the enzyme's direct GABA-catabolic role.
- term:
    id: GO:0031652
    label: positive regulation of heat generation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic transfer of a rodent-ortholog physiological phenotype. Too indirect to
      represent human ABAT function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Physiological phenotype transferred from the rodent ortholog; over-annotation.
- term:
    id: GO:0032024
    label: positive regulation of insulin secretion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Tissue-level regulatory phenotype transferred from the rodent ortholog; too indirect
      to represent human ABAT function.
- term:
    id: GO:0033602
    label: negative regulation of dopamine secretion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic transfer of a rodent-ortholog neurotransmission phenotype. Downstream
      consequence of GABA signalling, not a direct function of the enzyme.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Indirect neurotransmission phenotype transferred from the rodent ortholog;
      over-annotation.
- term:
    id: GO:0035094
    label: response to nicotine
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic transfer of a rodent-ortholog pharmacological-response phenotype. Not a
      direct function of human ABAT.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Pharmacological-response phenotype transferred from the rodent ortholog; too
      indirect.
- term:
    id: GO:0035640
    label: exploration behavior
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic transfer of a rodent-ortholog behavioural phenotype. Not a molecular
      function or direct role of the human enzyme.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Behavioural phenotype transferred from the rodent ortholog; over-annotation.
- term:
    id: GO:0042220
    label: response to cocaine
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic transfer of a rodent-ortholog pharmacological-response phenotype. Too
      indirect to represent human ABAT function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Pharmacological-response phenotype transferred from the rodent ortholog;
      over-annotation.
- term:
    id: GO:0045471
    label: response to ethanol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic transfer of a rodent-ortholog response phenotype. Not a direct function of
      human ABAT.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Response phenotype transferred from the rodent ortholog; over-annotation.
- term:
    id: GO:0045776
    label: negative regulation of blood pressure
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic transfer of a rodent-ortholog physiological phenotype. Too indirect to
      represent human ABAT function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Physiological phenotype transferred from the rodent ortholog; over-annotation.
- term:
    id: GO:0045964
    label: positive regulation of dopamine metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic transfer of a rodent-ortholog metabolic-regulation phenotype. Downstream
      of GABA signalling, not a direct function of the enzyme.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Indirect regulatory phenotype transferred from the rodent ortholog; over-annotation.
- term:
    id: GO:0050877
    label: nervous system process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0070474
    label: positive regulation of uterine smooth muscle contraction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic transfer of a rodent-ortholog physiological phenotype. Too indirect to
      represent human ABAT function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Physiological phenotype transferred from the rodent ortholog; over-annotation.
- term:
    id: GO:0097151
    label: positive regulation of inhibitory postsynaptic potential
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Indirect neurophysiological phenotype transferred from the rodent ortholog;
      over-annotation relative to the enzyme's direct GABA-catabolic role.
- term:
    id: GO:1902722
    label: positive regulation of prolactin secretion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic transfer of a rodent-ortholog endocrine phenotype. Too indirect to
      represent human ABAT function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Endocrine-regulation phenotype transferred from the rodent ortholog; over-annotation.
- term:
    id: GO:1904450
    label: positive regulation of aspartate secretion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic transfer of a rodent-ortholog neurotransmitter-secretion phenotype. Too
      indirect to represent human ABAT function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Indirect secretion phenotype transferred from the rodent ortholog; over-annotation.
- term:
    id: GO:0006540
    label: GABA shunt
  evidence_type: IDA
  original_reference_id: PMID:15528998
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: >-
      Directly supported experimental annotation for a core pathway of ABAT.
    supported_by:
    - reference_id: PMID:15528998
      supporting_text: "converts the major inhibitory neurotransmitter GABA to succinic"
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: >-
      Immunofluorescence-based (HPA) localization to mitochondrion. Consistent with the
      matrix localization established biochemically and by Reactome.
    action: ACCEPT
    reason: >-
      Correct localization; general term (the specific matrix term is also annotated).
    supported_by:
    - reference_id: file:human/ABAT/ABAT-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Mitochondrion matrix."
- term:
    id: GO:0034386
    label: 4-aminobutyrate:2-oxoglutarate transaminase activity
  evidence_type: IDA
  original_reference_id: PMID:15528998
  qualifier: contributes_to
  review:
    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.
    action: ACCEPT
    reason: >-
      Core molecular function, experimentally demonstrated; the contributes_to qualifier
      is appropriate for the obligate homodimer.
    supported_by:
    - reference_id: PMID:15528998
      supporting_text: "converts the major inhibitory neurotransmitter GABA to succinic"
    - reference_id: PMID:15528998
      supporting_text: "the Cys321 residue is essential for the catalytic function of GABA-T"
- term:
    id: GO:0050877
    label: nervous system process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      Plausible but indirect and very general; keep as a non-core biological role.
- term:
    id: GO:0047298
    label: (S)-3-amino-2-methylpropionate:2-oxoglutarate transaminase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      A genuine secondary activity (by similarity in human) rather than the physiological
      core function; retained as non-core.
    supported_by:
    - reference_id: file:human/ABAT/ABAT-uniprot.txt
      supporting_text: "AltName: Full=(S)-3-amino-2-methylpropionate transaminase"
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    summary: >-
      High-throughput (HTP) identification of ABAT as a member of the high-confidence
      human mitochondrial proteome (MitoCoP). Consistent with all other localization
      evidence.
    action: ACCEPT
    reason: >-
      Corroborates mitochondrial localization; general term, redundant with the matrix
      annotations.
    supported_by:
    - reference_id: PMID:34800366
      supporting_text: "mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)"
- term:
    id: GO:0034386
    label: 4-aminobutyrate:2-oxoglutarate transaminase activity
  evidence_type: IDA
  original_reference_id: PMID:10407778
  qualifier: enables
  review:
    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).
    action: ACCEPT
    reason: >-
      Core molecular function, experimentally demonstrated for the human enzyme.
    supported_by:
    - reference_id: PMID:10407778
      supporting_text: "Vmax was reduced to 25% of wild-type activity"
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-916855
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    reason: >-
      Well supported; matches UniProt (Mitochondrion matrix) and the Reactome reaction
      description.
    supported_by:
    - reference_id: file:human/ABAT/ABAT-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Mitochondrion matrix."
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: GO_REF:0000054
  qualifier: located_in
  review:
    summary: >-
      Localization of an expressed fusion protein (LIFEdb) to mitochondrion. Consistent
      with all other localization evidence.
    action: ACCEPT
    reason: >-
      Correct localization; general term, redundant with the matrix annotations.
    supported_by:
    - reference_id: file:human/ABAT/ABAT-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Mitochondrion matrix."
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: >-
      Sequence-similarity (ISS, from chicken Q9BGI0) assignment of mitochondrial
      localization. Consistent with all other localization evidence.
    action: ACCEPT
    reason: >-
      Correct localization; general term, redundant with the more specific matrix
      annotations.
    supported_by:
    - reference_id: file:human/ABAT/ABAT-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Mitochondrion matrix."
- term:
    id: GO:0032144
    label: 4-aminobutyrate transaminase complex
  evidence_type: IDA
  original_reference_id: PMID:15528998
  qualifier: part_of
  review:
    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.
    action: ACCEPT
    reason: >-
      Directly supported: ABAT is the obligate homodimeric GABA-transaminase complex.
    supported_by:
    - reference_id: PMID:15528998
      supporting_text: "involved in the formation of a disulfide link between two monomers"
- term:
    id: GO:0032145
    label: succinate-semialdehyde dehydrogenase binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0030170
    label: pyridoxal phosphate binding
  evidence_type: IDA
  original_reference_id: PMID:15650327
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: >-
      Core cofactor-binding function, experimentally demonstrated for the human enzyme.
    supported_by:
    - reference_id: PMID:15650327
      supporting_text: "is involved in binding PLP at the active site"
core_functions:
- description: >-
    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.
  molecular_function:
    id: GO:0034386
    label: 4-aminobutyrate:2-oxoglutarate transaminase activity
  directly_involved_in:
  - id: GO:0009450
    label: GABA catabolic process
  locations:
  - id: GO:0005759
    label: mitochondrial matrix
  supported_by:
  - reference_id: PMID:10407778
    supporting_text: "Vmax was reduced to 25% of wild-type activity"
  - reference_id: PMID:15528998
    supporting_text: "converts the major inhibitory neurotransmitter GABA to succinic"
- description: >-
    Pyridoxal-5'-phosphate cofactor binding at the active site (covalent Schiff base at
    Lys357), required for the transaminase catalytic mechanism.
  molecular_function:
    id: GO:0030170
    label: pyridoxal phosphate binding
  locations:
  - id: GO:0005759
    label: mitochondrial matrix
  supported_by:
  - reference_id: PMID:15650327
    supporting_text: "is involved in binding PLP at the active site"
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000054
  title: Gene Ontology annotation based on curation of intracellular localizations
    of expressed fusion proteins in living cells
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10407778
  title: 4-Aminobutyrate aminotransferase (GABA-transaminase) deficiency.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified. Reports recombinant human GABA-T enzymatic activity and the GABATD
      R220K variant (Vmax 25% of wild-type); supports the core transaminase activity and
      the disease association. Abstract-only in cache but the assayed enzyme is human ABAT.
- id: PMID:15528998
  title: Cysteine-321 of human brain GABA transaminase is involved in intersubunit
    cross-linking.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified. Characterizes human brain GABA-T as a key homodimeric enzyme of the
      GABA shunt (GABA -> succinic semialdehyde); Cys321 disulfide links the two monomers
      and is essential for activity. Supports GABA shunt, transaminase activity, and the
      homodimeric complex.
- id: PMID:15650327
  title: 'Site-directed mutagenesis of human brain GABA transaminase: lysine-357 is
    involved in cofactor binding at the active site.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified. Lys357 is essential for catalysis and for binding PLP at the active
      site; K357 mutants lack PLP absorption bands and activity. Supports the PLP-binding
      molecular function.
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics
    in cellular context.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified large-scale study (MitoCoP). ABAT is included in the high-confidence
      human mitochondrial proteome (supplementary tables); supports mitochondrial
      localization but is not gene-specific.
- id: Reactome:R-HSA-916855
  title: PXLP-K357-ABAT dimer:2Fe-2S transforms GABA to SUCCSA
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Reactome reaction describing ABAT converting GABA + 2-oxoglutarate to succinate
      semialdehyde + L-glutamate in the mitochondrial matrix; supports the core activity
      and matrix localization.
- id: file:human/ABAT/ABAT-uniprot.txt
  title: UniProtKB entry P80404 (GABT_HUMAN), 4-aminobutyrate aminotransferase, mitochondrial
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Curated UniProt record. Source for the reviewed catalytic activities (EC 2.6.1.19,
      EC 2.6.1.22), PLP and [2Fe-2S] cofactors, mitochondrial matrix localization, and the
      GABATD disease association.