id: P21549
gene_symbol: AGXT
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  AGXT encodes alanine--glyoxylate aminotransferase (AGT), a liver-specific,
  peroxisomal, pyridoxal-5'-phosphate (PLP)-dependent aminotransferase of the
  class-V PLP family. Its principal role is glyoxylate detoxification: it
  transaminates glyoxylate to glycine using L-alanine as the amino donor
  (glyoxylate + L-alanine -> glycine + pyruvate; EC 2.6.1.44), thereby
  preventing glyoxylate from being oxidised to oxalate. The same enzyme also
  catalyses the serine:pyruvate transamination (L-serine + pyruvate =
  3-hydroxypyruvate + L-alanine; EC 2.6.1.51), contributing to serine
  metabolism. AGT is an obligate homodimer whose N-terminal extension wraps over
  the neighbouring subunit, with PLP covalently bound to Lys209. In human
  hepatocytes AGT resides in the peroxisomal matrix, imported by the Pex5p
  receptor via an atypical C-terminal Lys-Lys-Leu (KKL) PTS1 together with
  ancillary targeting information. Loss of AGT activity causes primary
  hyperoxaluria type 1 (PH1), a severe autosomal-recessive calcium-oxalate stone
  disease with nephrolithiasis, nephrocalcinosis, systemic oxalosis and
  end-stage renal disease. A common minor-allele polymorphism (P11L) creates a
  cryptic N-terminal mitochondrial targeting sequence that, in combination with
  certain disease mutations (e.g. G170R), reroutes AGT from peroxisomes to
  mitochondria, where it can no longer detoxify peroxisomally generated
  glyoxylate.
existing_annotations:
- term:
    id: GO:0004760
    label: L-serine:pyruvate transaminase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Phylogenetic (IBA) assignment of serine:pyruvate transaminase activity
      (EC 2.6.1.51). This is a genuine, experimentally documented activity of
      human AGT, which catalyses L-serine + pyruvate = 3-hydroxypyruvate +
      L-alanine.
    action: ACCEPT
    reason: >-
      Serine:pyruvate transaminase activity is experimentally demonstrated for
      human AGT and encoded as EC 2.6.1.51 (SPT). It is a real, though secondary,
      catalytic activity relative to the core glyoxylate-detoxifying reaction.
    supported_by:
    - reference_id: PMID:10347152
      supporting_text: >-
        these results suggest that SPT/AGT in this organelle plays dual roles in
        the metabolism of glyoxylate and serine.
- term:
    id: GO:0006545
    label: glycine biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Phylogenetic (IBA) assignment of glycine biosynthetic process. AGT forms
      glycine as the product of glyoxylate transamination, so it contributes to
      glycine biosynthesis by transamination of glyoxylate.
    action: ACCEPT
    reason: >-
      The physiological reaction produces glycine from glyoxylate, making glycine
      biosynthesis a direct consequence of AGT catalysis (this is the core
      detoxification reaction viewed from the product side).
    supported_by:
    - reference_id: PMID:17696873
      supporting_text: >-
        the enzyme is highly specific for catalysing glyoxylate to glycine
        processing, thereby playing a key role in glyoxylate detoxification
- term:
    id: GO:0009436
    label: glyoxylate catabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Phylogenetic (IBA) assignment of glyoxylate catabolic process. AGT
      catabolises glyoxylate by transaminating it to glycine; this is its core
      biological role.
    action: ACCEPT
    reason: >-
      Well supported core biological process: glyoxylate is consumed
      (detoxified) by transamination to glycine. This is a central, non-redundant
      role of AGT in the liver peroxisome.
    supported_by:
    - reference_id: PMID:23229545
      supporting_text: >-
        Failure to transaminate glyoxylate to glycine within the peroxisomes,
        allows glyoxylate to diffuse into the cytosol where it is oxidized to the
        metabolic end product oxalate
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetic (IBA) assignment placing AGT active in the peroxisome. In
      human hepatocytes AGT is a peroxisomal matrix enzyme.
    action: ACCEPT
    reason: >-
      Human AGT is peroxisomal and this is where it exerts its glyoxylate
      detoxification function; the is_active_in qualifier is appropriate for the
      compartment where the enzyme acts.
    supported_by:
    - reference_id: PMID:3418107
      supporting_text: >-
        immunoreactive AGT protein was confined to peroxisomes, where it was
        randomly dispersed throughout the peroxisomal matrix
- term:
    id: GO:0008453
    label: L-alanine:glyoxylate transaminase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Phylogenetic (IBA) assignment of alanine:glyoxylate transaminase activity
      (EC 2.6.1.44), the core molecular function of AGT.
    action: ACCEPT
    reason: >-
      This is the central, experimentally established catalytic activity of AGT
      and is the correct molecular function term. The IBA is concordant with
      multiple direct assays.
    supported_by:
    - reference_id: file:human/AGXT/AGXT-uniprot.txt
      supporting_text: >-
        Peroxisomal aminotransferase that catalyzes the transamination of
        glyoxylate to glycine and contributes to the glyoxylate detoxification
- term:
    id: GO:0004760
    label: L-serine:pyruvate transaminase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Electronic (RHEA/EC 2.6.1.51) assignment of serine:pyruvate transaminase
      activity, consistent with the experimentally documented SPT activity.
    action: ACCEPT
    reason: >-
      The EC 2.6.1.51 mapping is correct; AGT genuinely catalyses this reaction.
      Accept as a valid secondary activity.
    supported_by:
    - reference_id: file:human/AGXT/AGXT-uniprot.txt
      supporting_text: >-
        Reaction=L-serine + pyruvate = 3-hydroxypyruvate + L-alanine
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: >-
      Electronic (ARBA) assignment to cytoplasm. Human AGT is a peroxisomal
      matrix enzyme; a generic cytoplasm assignment reflects a default
      localization rather than the specific compartment.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Human AGT is imported into peroxisomes and acts in the peroxisomal matrix;
      only newly synthesised, not-yet-imported protein is transiently cytosolic.
      A bare cytoplasm term is uninformative and over-general given the strong
      experimental peroxisome localization; the peroxisome/peroxisomal matrix
      terms are the informative ones.
    supported_by:
    - reference_id: file:human/AGXT/AGXT-uniprot.txt
      supporting_text: >-
        SUBCELLULAR LOCATION: Peroxisome
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Electronic (UniProt Subcellular Location keyword mapping) assignment to
      peroxisome, concordant with strong experimental evidence.
    action: ACCEPT
    reason: >-
      Correct localization for human AGT, supported by direct immunocytochemistry
      and biochemical fractionation.
    supported_by:
    - reference_id: file:human/AGXT/AGXT-uniprot.txt
      supporting_text: >-
        SUBCELLULAR LOCATION: Peroxisome
- term:
    id: GO:0008453
    label: L-alanine:glyoxylate transaminase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Electronic (RHEA/EC 2.6.1.44) assignment of alanine:glyoxylate transaminase
      activity, the core molecular function.
    action: ACCEPT
    reason: >-
      The EC 2.6.1.44 / RHEA:24248 mapping correctly captures the core catalytic
      activity of AGT.
    supported_by:
    - reference_id: file:human/AGXT/AGXT-uniprot.txt
      supporting_text: >-
        Reaction=glyoxylate + L-alanine = glycine + pyruvate
- term:
    id: GO:0047635
    label: L-alanine:oxo-acid transaminase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    summary: >-
      Electronic (ARBA) assignment of the broad parent term L-alanine:oxo-acid
      transaminase activity. AGT does use L-alanine as amino donor toward
      oxo-acid acceptors (glyoxylate, pyruvate), but this term is more general
      than the specific alanine:glyoxylate activity.
    action: MODIFY
    reason: >-
      The specific, experimentally established activity is alanine:glyoxylate
      transaminase (GO:0008453); this generic L-alanine:oxo-acid transaminase
      term is a less-informative parent. Replace with the specific term already
      annotated.
    proposed_replacement_terms:
    - id: GO:0008453
      label: L-alanine:glyoxylate transaminase activity
    supported_by:
    - reference_id: file:human/AGXT/AGXT-uniprot.txt
      supporting_text: >-
        Reaction=glyoxylate + L-alanine = glycine + pyruvate
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22529745
  qualifier: enables
  review:
    summary: >-
      IntAct-derived protein binding annotation from the AGT-Pex5p structural
      study. The interaction (AGT with the peroxisomal import receptor PEX5) is
      biologically meaningful (peroxisomal targeting), but the bare protein
      binding term does not convey a molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Per curation guidance, bare protein binding (GO:0005515) is uninformative.
      The PEX5 interaction underlies peroxisomal import and would be better
      represented as targeting/cargo-receptor biology rather than a generic MF;
      the informative catalytic and localization terms already capture AGT
      function. Kept (not removed) as it records a real IPI interaction.
    supported_by:
    - reference_id: PMID:22529745
      supporting_text: >-
        we have determined the crystal structure of the respective
        cargo-receptor complex
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: >-
      High-throughput yeast two-hybrid (HuRI reference interactome) protein
      binding hits. Most partners are keratins/keratin-associated proteins and
      transcription factors with no established biological relationship to AGT
      hepatic glyoxylate metabolism.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Bare protein binding from a proteome-scale Y2H screen is uninformative and
      the specific partners are not biologically connected to AGT function.
      Retained as a record of the systematic interactome data rather than removed.
    supported_by:
    - reference_id: PMID:32296183
      supporting_text: >-
        reference interactome map of human binary protein interactions, or 'HuRI'
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:12899834
  qualifier: enables
  review:
    summary: >-
      Identical protein binding reflecting the biologically real AGT homodimer,
      here from the crystal structure showing the dimeric enzyme.
    action: ACCEPT
    reason: >-
      AGT is an obligate homodimer required for catalytic activity; identical
      protein binding correctly captures self-association and is informative
      (unlike bare protein binding).
    supported_by:
    - reference_id: PMID:12899834
      supporting_text: >-
        crystal structure of normal human AGT complexed to the competitive
        inhibitor amino-oxyacetic acid
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:22529745
  qualifier: enables
  review:
    summary: >-
      Identical protein binding (self-association) consistent with the AGT
      homodimer observed in the Pex5p-(AGT)2-Pex5p assembly.
    action: ACCEPT
    reason: >-
      Reflects the functionally required homodimer; informative self-interaction
      term.
    supported_by:
    - reference_id: PMID:22529745
      supporting_text: >-
        forms an elongated Pex5p-(AGT)2-Pex5p assembly
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: >-
      Identical protein binding self-interaction reported in the HuRI Y2H map,
      consistent with the known AGT homodimer.
    action: ACCEPT
    reason: >-
      Consistent with the obligate homodimer; a self-interaction term is
      informative about the quaternary structure.
    supported_by:
    - reference_id: file:human/AGXT/AGXT-uniprot.txt
      supporting_text: >-
        SUBUNIT: Homodimer
- term:
    id: GO:0006565
    label: L-serine catabolic process
  evidence_type: IDA
  original_reference_id: PMID:10347152
  qualifier: involved_in
  review:
    summary: >-
      Direct-assay assignment of L-serine catabolic process from flux studies
      showing AGT/SPT contributes to serine metabolism via serine:pyruvate
      transamination.
    action: KEEP_AS_NON_CORE
    reason: >-
      Serine catabolism through the SPT activity is a genuine but secondary role
      of AGT; the core physiological function is glyoxylate detoxification. Kept
      as non-core.
    supported_by:
    - reference_id: PMID:10347152
      supporting_text: >-
        flux through serine dehydratase accounted for only traces, and that
        through SPT/AGT substantially contributed
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: EXP
  original_reference_id: PMID:23229545
  qualifier: located_in
  review:
    summary: >-
      Experimental localization of AGT to peroxisomes (wild-type AGT is
      peroxisomal; disease mutants on the minor allele are rerouted to
      mitochondria).
    action: ACCEPT
    reason: >-
      Directly supported experimental peroxisome localization; core compartment.
    supported_by:
    - reference_id: PMID:23229545
      supporting_text: >-
        the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: EXP
  original_reference_id: PMID:24055001
  qualifier: located_in
  review:
    summary: >-
      Experimental localization to peroxisomes; Gly161 mutants instead aggregate
      in the cytosol, confirming that wild-type AGT is peroxisomal.
    action: ACCEPT
    reason: >-
      Supports peroxisomal localization of wild-type AGT.
    supported_by:
    - reference_id: PMID:24055001
      supporting_text: >-
        inherited mutations on liver peroxisomal alanine:glyoxylate
        aminotransferase
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: EXP
  original_reference_id: PMID:26149463
  qualifier: located_in
  review:
    summary: >-
      Experimental localization to peroxisomes; the G47R-Mi mutant is partly
      mistargeted to mitochondria but wild-type/rescued protein is peroxisomal.
    action: ACCEPT
    reason: >-
      Confirms peroxisomal localization of AGT.
    supported_by:
    - reference_id: PMID:26149463
      supporting_text: >-
        reroutes all the protein to peroxisomes
- term:
    id: GO:0008453
    label: L-alanine:glyoxylate transaminase activity
  evidence_type: EXP
  original_reference_id: PMID:23229545
  qualifier: enables
  review:
    summary: >-
      Experimental alanine:glyoxylate transaminase activity (core catalytic
      function; the mistargeted mutants that retain dimer form are catalytically
      active).
    action: ACCEPT
    reason: >-
      Core molecular function, directly assayed.
    supported_by:
    - reference_id: PMID:23229545
      supporting_text: >-
        the G170R, I244T, and F152I mutants are able to form dimers and are
        catalytically active
- term:
    id: GO:0008453
    label: L-alanine:glyoxylate transaminase activity
  evidence_type: EXP
  original_reference_id: PMID:24055001
  qualifier: enables
  review:
    summary: >-
      Experimental alanine:glyoxylate transaminase activity assayed on
      recombinant AGT and Gly161 variants.
    action: ACCEPT
    reason: >-
      Core molecular function, directly assayed.
    supported_by:
    - reference_id: PMID:24055001
      supporting_text: >-
        biochemical analyses on the purified recombinant proteins
- term:
    id: GO:0008453
    label: L-alanine:glyoxylate transaminase activity
  evidence_type: EXP
  original_reference_id: PMID:26149463
  qualifier: enables
  review:
    summary: >-
      Experimental alanine:glyoxylate transaminase activity measured for
      recombinant wild-type and G47R-Mi AGT.
    action: ACCEPT
    reason: >-
      Core molecular function, directly assayed.
    supported_by:
    - reference_id: PMID:26149463
      supporting_text: >-
        the recombinant purified G47R-Mi variant exhibits only a 2.5-fold
        reduction of its kcat
- term:
    id: GO:0004760
    label: L-serine:pyruvate transaminase activity
  evidence_type: IDA
  original_reference_id: PMID:10347152
  qualifier: enables
  review:
    summary: >-
      Direct-assay serine:pyruvate transaminase activity (EC 2.6.1.51), a real
      secondary activity of AGT.
    action: ACCEPT
    reason: >-
      Experimentally established SPT activity; valid secondary molecular function.
    supported_by:
    - reference_id: PMID:10347152
      supporting_text: >-
        serine:pyruvate/alanine:glyoxylate aminotransferase (SPT/AGT)
- term:
    id: GO:0046487
    label: glyoxylate metabolic process
  evidence_type: IDA
  original_reference_id: PMID:12777626
  qualifier: involved_in
  review:
    summary: >-
      Direct-assay assignment to glyoxylate metabolic process; AGT is central to
      hepatic glyoxylate metabolism.
    action: ACCEPT
    reason: >-
      Correct and core: AGT participates in glyoxylate metabolism by
      transaminating glyoxylate. Slightly more general than glyoxylate catabolic
      process but valid.
    supported_by:
    - reference_id: PMID:12777626
      supporting_text: >-
        an inborn error of metabolism resulting from a deficiency of
        alanine:glyoxylate aminotransferase
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IDA
  original_reference_id: PMID:10960483
  qualifier: located_in
  review:
    summary: >-
      Direct-assay peroxisome localization of AGT.
    action: ACCEPT
    reason: >-
      Core peroxisomal localization; supported by subcellular localization
      analysis of purified/expressed AGT.
    supported_by:
    - reference_id: PMID:10960483
      supporting_text: >-
        peroxisome-to-mitochondrion AGT mistargeting in mammalian cells
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IDA
  original_reference_id: PMID:12777626
  qualifier: located_in
  review:
    summary: >-
      Direct-assay peroxisome localization; the AGXT*LTM protein colocalises with
      the peroxisomal marker PMP70.
    action: ACCEPT
    reason: >-
      Directly supported peroxisomal localization.
    supported_by:
    - reference_id: PMID:12777626
      supporting_text: >-
        the AGXT*LTM protein was present in the peroxisomes
- term:
    id: GO:0008453
    label: L-alanine:glyoxylate transaminase activity
  evidence_type: IDA
  original_reference_id: PMID:10960483
  qualifier: enables
  review:
    summary: >-
      Direct-assay alanine:glyoxylate transaminase activity of purified
      recombinant AGT.
    action: ACCEPT
    reason: >-
      Core molecular function, directly assayed on purified enzyme.
    supported_by:
    - reference_id: PMID:10960483
      supporting_text: >-
        normal human His-tagged AGT can be expressed at high levels in
        Escherichia coli and purified in a correctly folded, dimerized and
        catalytically active state
- term:
    id: GO:0008453
    label: L-alanine:glyoxylate transaminase activity
  evidence_type: IMP
  original_reference_id: PMID:12777626
  qualifier: enables
  review:
    summary: >-
      Mutation-based (IMP) support for alanine:glyoxylate transaminase activity;
      the L11P/I244T combination causes loss of enzymatic activity.
    action: ACCEPT
    reason: >-
      Supports the core catalytic function via loss-of-activity phenotype of
      disease variants.
    supported_by:
    - reference_id: PMID:12777626
      supporting_text: >-
        it resulted in loss of enzymatic activity in soluble cell extracts
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:10960483
  qualifier: enables
  review:
    summary: >-
      Direct-assay protein homodimerization; purified AGT is a catalytically
      active dimer.
    action: ACCEPT
    reason: >-
      AGT is an obligate homodimer required for activity; homodimerization is a
      real, informative property (kept as non-core relative to catalysis, but a
      valid structural/functional term).
    supported_by:
    - reference_id: PMID:10960483
      supporting_text: >-
        purified in a correctly folded, dimerized and catalytically active state
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:12777626
  qualifier: enables
  review:
    summary: >-
      Direct-assay homodimerization; AGT variants dimerize (cross-linking gives
      ~90 kDa dimer bands).
    action: ACCEPT
    reason: >-
      Supports the obligate homodimer quaternary structure.
    supported_by:
    - reference_id: PMID:12777626
      supporting_text: >-
        Cross-linking of TnT products of all variants tested resulted in ~90-kDa
        bands, consistent with functional dimerization
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9033235
  qualifier: located_in
  review:
    summary: >-
      Reactome (TAS) cytosol assignment tied to the peroxisomal protein import
      reaction, in which newly synthesised AGT cargo is cytosolic prior to Pex5p
      translocation.
    action: KEEP_AS_NON_CORE
    reason: >-
      Human AGT functions in the peroxisomal matrix; its cytosolic presence is a
      transient pre-import stage captured by the Reactome import model. Kept as
      non-core context rather than as a functional location.
    supported_by:
    - reference_id: PMID:22529745
      supporting_text: >-
        the absence of AGT in hepatic peroxisomes, owing to either dysfunction or
        mistargeting of AGT, causes glyoxylate to escape into the cytosol
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9033236
  qualifier: located_in
  review:
    summary: >-
      Reactome (TAS) cytosol assignment from the PEX5:cargo docking-module import
      reaction; reflects the pre-import cytosolic stage of AGT.
    action: KEEP_AS_NON_CORE
    reason: >-
      As above, cytosol reflects the transient pre-peroxisomal-import stage of
      AGT within the Reactome import pathway, not its functional compartment.
    supported_by:
    - reference_id: PMID:22529745
      supporting_text: >-
        which is required for translocation of the enzyme into peroxisomes
- term:
    id: GO:0008453
    label: L-alanine:glyoxylate transaminase activity
  evidence_type: IDA
  original_reference_id: PMID:16971151
  qualifier: enables
  review:
    summary: >-
      Direct-assay alanine:glyoxylate transaminase activity across a spectrum of
      recombinant AGT variants.
    action: ACCEPT
    reason: >-
      Core molecular function, directly assayed.
    supported_by:
    - reference_id: PMID:16971151
      supporting_text: >-
        We have investigated their effects on enzyme activity, dimerization,
        aggregation, and turnover.
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:16971151
  qualifier: enables
  review:
    summary: >-
      Direct-assay homodimerization; dimerization failure was a frequent
      consequence of PH1 missense mutations, confirming AGT normally homodimerizes.
    action: ACCEPT
    reason: >-
      Supports the obligate homodimer; informative structural property.
    supported_by:
    - reference_id: PMID:16971151
      supporting_text: >-
        Dimerization failure was a frequent observation
- term:
    id: GO:0005782
    label: peroxisomal matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-389684
  qualifier: located_in
  review:
    summary: >-
      Reactome (TAS) peroxisomal matrix localization tied to the "glyoxylate +
      alanine => glycine + pyruvate [peroxisome]" reaction; this is the correct
      functional compartment for AGT.
    action: ACCEPT
    reason: >-
      Peroxisomal matrix is the precise compartment where AGT acts; strongly
      supported by immunocytochemistry.
    supported_by:
    - reference_id: PMID:3418107
      supporting_text: >-
        randomly dispersed throughout the peroxisomal matrix
- term:
    id: GO:0005782
    label: peroxisomal matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9033235
  qualifier: located_in
  review:
    summary: >-
      Reactome (TAS) peroxisomal matrix localization from the peroxisomal cargo
      translocation reaction; correct functional compartment for AGT.
    action: ACCEPT
    reason: >-
      Correct precise compartment (peroxisomal matrix).
    supported_by:
    - reference_id: PMID:3418107
      supporting_text: >-
        randomly dispersed throughout the peroxisomal matrix
- term:
    id: GO:0008453
    label: L-alanine:glyoxylate transaminase activity
  evidence_type: IDA
  original_reference_id: PMID:18492492
  qualifier: enables
  review:
    summary: >-
      Direct-assay of the main transaminase reaction of human liver peroxisomal
      AGT.
    action: ACCEPT
    reason: >-
      Core catalytic function, directly assayed.
    supported_by:
    - reference_id: PMID:18492492
      supporting_text: >-
        In addition to the main transaminase reaction, the pyridoxal
        5'-phosphate-dependent enzyme human liver peroxisomal alanine:glyoxylate
        aminotransferase (AGT)
- term:
    id: GO:0008483
    label: transaminase activity
  evidence_type: IDA
  original_reference_id: PMID:18492492
  qualifier: enables
  review:
    summary: >-
      Direct-assay assignment of the generic parent term transaminase activity.
      AGT's specific activity is alanine:glyoxylate transaminase.
    action: MODIFY
    reason: >-
      transaminase activity (GO:0008483) is a broad parent; the specific,
      experimentally established activity is alanine:glyoxylate transaminase
      (GO:0008453). Replace with the specific term.
    proposed_replacement_terms:
    - id: GO:0008453
      label: L-alanine:glyoxylate transaminase activity
    supported_by:
    - reference_id: PMID:18492492
      supporting_text: >-
        In addition to the main transaminase reaction
- term:
    id: GO:0016597
    label: amino acid binding
  evidence_type: IDA
  original_reference_id: PMID:18492492
  qualifier: enables
  review:
    summary: >-
      Direct-assay amino acid binding; AGT binds its amino-acid substrates
      (L-alanine, L-serine, L-cysteine) at the active site, with calculated
      interaction energies for docked amino acids.
    action: ACCEPT
    reason: >-
      Substrate (amino acid) binding is experimentally supported and informative
      about the enzyme's active-site chemistry.
    supported_by:
    - reference_id: PMID:18492492
      supporting_text: >-
        the calculated interaction energies of the L-cysteine, L-alanine and
        L-serine docked at the active site of AGT
- term:
    id: GO:0019448
    label: L-cysteine catabolic process
  evidence_type: IDA
  original_reference_id: PMID:18492492
  qualifier: involved_in
  review:
    summary: >-
      Direct-assay L-cysteine catabolic process from in vitro demonstration that
      AGT half-transaminates and beta-eliminates L-cysteine.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is an in vitro side reaction (kcat ~200-fold lower than L-alanine),
      not the physiological glyoxylate-detoxification role. Kept as non-core
      rather than removed, since the activity is experimentally documented.
    supported_by:
    - reference_id: PMID:18492492
      supporting_text: >-
        the occurrence of both beta-elimination and half-transamination of
        L-cysteine together with the pyruvate transamination
- term:
    id: GO:0042853
    label: L-alanine catabolic process
  evidence_type: IDA
  original_reference_id: PMID:18492492
  qualifier: involved_in
  review:
    summary: >-
      Direct-assay L-alanine catabolic process; L-alanine is the physiological
      amino donor consumed in the AGT reaction (converted to pyruvate).
    action: KEEP_AS_NON_CORE
    reason: >-
      L-alanine is co-consumed as the amino donor of the core reaction, so its
      catabolism is a real by-product of AGT activity; secondary to the
      glyoxylate-detoxification framing. Kept as non-core.
    supported_by:
    - reference_id: PMID:18492492
      supporting_text: >-
        the physiological transaminase reaction with L-alanine
- term:
    id: GO:0008453
    label: L-alanine:glyoxylate transaminase activity
  evidence_type: IDA
  original_reference_id: PMID:17696873
  qualifier: enables
  review:
    summary: >-
      Direct-assay characterization of AGT transaminase kinetics establishing
      high specificity for glyoxylate-to-glycine processing.
    action: ACCEPT
    reason: >-
      Core molecular function, directly measured (steady-state and
      pre-steady-state kinetics).
    supported_by:
    - reference_id: PMID:17696873
      supporting_text: >-
        the enzyme is highly specific for catalysing glyoxylate to glycine
        processing
- term:
    id: GO:0030170
    label: pyridoxal phosphate binding
  evidence_type: IDA
  original_reference_id: PMID:17696873
  qualifier: enables
  review:
    summary: >-
      Direct-assay PLP binding; AGT binds 2 mol PLP per dimer, and PLP-binding
      affinity is measured for wild-type and G82E.
    action: ACCEPT
    reason: >-
      PLP is the essential cofactor of AGT; PLP binding is experimentally
      demonstrated and is a valid (secondary) molecular function supporting
      catalysis.
    supported_by:
    - reference_id: PMID:17696873
      supporting_text: >-
        the G82E variant is able to bind 2 mol PLP/dimer
- term:
    id: GO:0042853
    label: L-alanine catabolic process
  evidence_type: IDA
  original_reference_id: PMID:17696873
  qualifier: involved_in
  review:
    summary: >-
      Direct-assay L-alanine catabolic process; L-alanine is the amino donor in
      the forward AGT reaction whose kinetics are characterized here.
    action: KEEP_AS_NON_CORE
    reason: >-
      L-alanine is the co-substrate/amino donor of the core reaction; its
      catabolism is a by-product. Kept as non-core.
    supported_by:
    - reference_id: PMID:17696873
      supporting_text: >-
        the steady-state kinetic parameters of the forward and reverse reactions
- term:
    id: GO:0008483
    label: transaminase activity
  evidence_type: IDA
  original_reference_id: PMID:20133649
  qualifier: enables
  review:
    summary: >-
      Direct-assay assignment of the generic parent transaminase activity from
      characterization of G41 variants and their catalytic efficiency.
    action: MODIFY
    reason: >-
      Generic parent term; the specific activity is alanine:glyoxylate
      transaminase (GO:0008453). Replace with the specific term.
    proposed_replacement_terms:
    - id: GO:0008453
      label: L-alanine:glyoxylate transaminase activity
    supported_by:
    - reference_id: PMID:20133649
      supporting_text: >-
        reduced coenzyme binding affinity, and catalytic efficiency
- term:
    id: GO:0030170
    label: pyridoxal phosphate binding
  evidence_type: IDA
  original_reference_id: PMID:20133649
  qualifier: enables
  review:
    summary: >-
      Direct-assay PLP (coenzyme) binding; G41 variants show reduced coenzyme
      binding affinity relative to wild-type AGT.
    action: ACCEPT
    reason: >-
      Supports the essential PLP-cofactor binding property of AGT.
    supported_by:
    - reference_id: PMID:20133649
      supporting_text: >-
        reduced coenzyme binding affinity
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:20133649
  qualifier: enables
  review:
    summary: >-
      Direct-assay homodimerization; G41 mutations increase the dimer-monomer
      dissociation constant, confirming that wild-type AGT forms a dimer.
    action: ACCEPT
    reason: >-
      Supports the obligate homodimer quaternary structure of AGT.
    supported_by:
    - reference_id: PMID:20133649
      supporting_text: >-
        increasing the dimer-monomer equilibrium dissociation constant
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IDA
  original_reference_id: PMID:9053548
  qualifier: located_in
  review:
    summary: >-
      Direct immunocytochemical localization of AGT to peroxisomes in human liver.
    action: ACCEPT
    reason: >-
      Supports peroxisomal localization in situ.
    supported_by:
    - reference_id: PMID:9053548
      supporting_text: >-
        alanine : glyoxylate aminotransferase
- term:
    id: GO:0005782
    label: peroxisomal matrix
  evidence_type: IDA
  original_reference_id: PMID:3418107
  qualifier: located_in
  review:
    summary: >-
      Direct immunocytochemistry showing AGT confined to peroxisomes, dispersed
      throughout the peroxisomal matrix.
    action: ACCEPT
    reason: >-
      Precise, directly supported compartment (peroxisomal matrix).
    supported_by:
    - reference_id: PMID:3418107
      supporting_text: >-
        confined to peroxisomes, where it was randomly dispersed throughout the
        peroxisomal matrix
- term:
    id: GO:0006545
    label: glycine biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:22198249
  qualifier: involved_in
  review:
    summary: >-
      Direct-assay assignment to glycine biosynthetic process; glycine is the
      product of the AGT transamination reaction.
    action: ACCEPT
    reason: >-
      Glycine formation is a direct product of the core AGT reaction; valid BP.
    supported_by:
    - reference_id: PMID:22198249
      supporting_text: >-
        Alanine:glyoxylate aminotransferase (AGT) is a pyridoxal-phosphate
        (PLP)-dependent enzyme
- term:
    id: GO:0008453
    label: L-alanine:glyoxylate transaminase activity
  evidence_type: IDA
  original_reference_id: PMID:22198249
  qualifier: enables
  review:
    summary: >-
      Direct-assay alanine:glyoxylate transaminase activity; full-length AGT is
      catalytically active whereas the N-terminal-deleted form loses activity.
    action: ACCEPT
    reason: >-
      Core molecular function, directly assayed.
    supported_by:
    - reference_id: PMID:22198249
      supporting_text: >-
        The purified soluble fraction showed reduced affinity for PLP and greatly
        reduced catalytic activity.
- term:
    id: GO:0009436
    label: glyoxylate catabolic process
  evidence_type: IDA
  original_reference_id: PMID:22198249
  qualifier: involved_in
  review:
    summary: >-
      Direct-assay assignment to glyoxylate catabolic process; AGT detoxifies
      glyoxylate by transamination.
    action: ACCEPT
    reason: >-
      Core biological process (glyoxylate consumption/detoxification).
    supported_by:
    - reference_id: PMID:22198249
      supporting_text: >-
        the hereditary kidney stone disease primary hyperoxaluria type 1
- term:
    id: GO:0042853
    label: L-alanine catabolic process
  evidence_type: IDA
  original_reference_id: PMID:22198249
  qualifier: involved_in
  review:
    summary: >-
      Direct-assay L-alanine catabolic process; L-alanine is the amino donor
      consumed in the AGT reaction.
    action: KEEP_AS_NON_CORE
    reason: >-
      L-alanine is co-consumed as the amino donor of the core reaction; secondary
      framing. Kept as non-core.
    supported_by:
    - reference_id: PMID:22198249
      supporting_text: >-
        the active dimeric structure of liver peroxisomal alanine:glyoxylate
        aminotransferase
- term:
    id: GO:0005782
    label: peroxisomal matrix
  evidence_type: IDA
  original_reference_id: PMID:22198249
  qualifier: located_in
  review:
    summary: >-
      Direct-assay peroxisomal matrix localization; the truncated construct is
      normally targeted to peroxisomes where it forms matrix aggregates.
    action: ACCEPT
    reason: >-
      Supports peroxisomal (matrix) localization of AGT.
    supported_by:
    - reference_id: PMID:22198249
      supporting_text: >-
        the truncated construct was normally targeted to peroxisomes
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IDA
  original_reference_id: PMID:7813517
  qualifier: located_in
  review:
    summary: >-
      Direct immunoelectron microscopy showing that in human liver essentially
      all AGT is concentrated within peroxisomes (type I distribution).
    action: ACCEPT
    reason: >-
      Supports peroxisomal localization of human AGT in situ.
    supported_by:
    - reference_id: PMID:7813517
      supporting_text: >-
        all, or nearly all, of the immunoreactive AGT1 was concentrated within
        the peroxisomes
- term:
    id: GO:0030170
    label: pyridoxal phosphate binding
  evidence_type: IMP
  original_reference_id: PMID:15802217
  qualifier: enables
  review:
    summary: >-
      Mutation/reconstitution (IMP) support for PLP binding; KM values for PLP
      were determined by reconstitution of apo-AGT, with the minor allele (I340M)
      reducing PLP affinity.
    action: ACCEPT
    reason: >-
      Supports the essential PLP-cofactor binding property of AGT via apoenzyme
      reconstitution and variant analysis.
    supported_by:
    - reference_id: PMID:15802217
      supporting_text: >-
        K(M)s for PLP were determined by reconstitution of the apoenzyme
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:12899834
  qualifier: enables
  review:
    summary: >-
      Direct structural (crystallographic) support for homodimerization; the AGT
      crystal structure is a dimer.
    action: ACCEPT
    reason: >-
      Supports the obligate homodimer quaternary structure.
    supported_by:
    - reference_id: PMID:12899834
      supporting_text: >-
        in terms of AGT tertiary and quaternary conformation
- term:
    id: GO:0046487
    label: glyoxylate metabolic process
  evidence_type: IMP
  original_reference_id: PMID:3709805
  qualifier: involved_in
  review:
    summary: >-
      Patient (IMP) evidence: peroxisomal AGT deficiency in PH1 patients disrupts
      glyoxylate metabolism, establishing AGT's role in this process.
    action: ACCEPT
    reason: >-
      Deficiency of AGT causes the glyoxylate-metabolism disorder PH1; core BP.
    supported_by:
    - reference_id: PMID:3709805
      supporting_text: >-
        there was a complete absence of peroxisomal alanine:glyoxylate
        aminotransferase
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15911627
  qualifier: enables
  review:
    summary: >-
      IntAct protein binding from a two-hybrid study showing human AGT interacts
      with the peroxisomal import receptor Pex5p. Biologically meaningful
      (targeting), but bare protein binding is uninformative as an MF.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Per curation guidance, bare protein binding (GO:0005515) is uninformative.
      The AGT-Pex5p interaction underlies peroxisomal import and is better
      captured as targeting biology; retained (not removed) as it records a real
      IPI. The PEX5 interaction is the biologically relevant partner here.
    supported_by:
    - reference_id: PMID:15911627
      supporting_text: >-
        human AGT interacts with human Pex5p in mammalian cells, but not yeast
        cells
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IDA
  original_reference_id: PMID:3709805
  qualifier: located_in
  review:
    summary: >-
      Direct subcellular-fractionation evidence localizing AGT to peroxisomes;
      PH1 patient liver shows complete absence of peroxisomal AGT.
    action: ACCEPT
    reason: >-
      Supports peroxisomal localization of AGT.
    supported_by:
    - reference_id: PMID:3709805
      supporting_text: >-
        there was a complete absence of peroxisomal alanine:glyoxylate
        aminotransferase
- term:
    id: GO:0008453
    label: L-alanine:glyoxylate transaminase activity
  evidence_type: TAS
  original_reference_id: PMID:2363689
  qualifier: enables
  review:
    summary: >-
      Author-statement (TAS) assignment of alanine:glyoxylate transaminase
      activity for human peroxisomal AGT.
    action: ACCEPT
    reason: >-
      Core molecular function; consistent with all direct assays.
    supported_by:
    - reference_id: PMID:2363689
      supporting_text: >-
        Human peroxisomal L-alanine: glyoxylate aminotransferase
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IDA
  original_reference_id: PMID:1703535
  qualifier: located_in
  review:
    summary: >-
      Direct-assay peroxisome localization; AGT is described as the "normally
      peroxisomal enzyme", mistargeted to mitochondria in some PH1 patients.
    action: ACCEPT
    reason: >-
      Supports the peroxisomal localization of wild-type AGT.
    supported_by:
    - reference_id: PMID:1703535
      supporting_text: >-
        the normally peroxisomal enzyme alanine/glyoxylate aminotransferase (AGT)
core_functions:
- description: >-
    Peroxisomal PLP-dependent alanine:glyoxylate transaminase that detoxifies
    glyoxylate by transaminating it to glycine using L-alanine as amino donor
    (glyoxylate + L-alanine -> glycine + pyruvate), preventing oxalate formation.
  molecular_function:
    id: GO:0008453
    label: L-alanine:glyoxylate transaminase activity
  directly_involved_in:
  - id: GO:0009436
    label: glyoxylate catabolic process
  locations:
  - id: GO:0005777
    label: peroxisome
  supported_by:
  - reference_id: PMID:17696873
    supporting_text: >-
      the enzyme is highly specific for catalysing glyoxylate to glycine
      processing, thereby playing a key role in glyoxylate detoxification
  - reference_id: PMID:23229545
    supporting_text: >-
      Failure to transaminate glyoxylate to glycine within the peroxisomes,
      allows glyoxylate to diffuse into the cytosol where it is oxidized to the
      metabolic end product oxalate
- description: >-
    Formation of glycine as the product of peroxisomal glyoxylate transamination,
    i.e. glycine biosynthesis by transamination of glyoxylate.
  molecular_function:
    id: GO:0008453
    label: L-alanine:glyoxylate transaminase activity
  directly_involved_in:
  - id: GO:0006545
    label: glycine biosynthetic process
  locations:
  - id: GO:0005777
    label: peroxisome
  supported_by:
  - reference_id: PMID:22198249
    supporting_text: >-
      the active dimeric structure of liver peroxisomal alanine:glyoxylate
      aminotransferase
  - reference_id: PMID:17696873
    supporting_text: >-
      the enzyme is highly specific for catalysing glyoxylate to glycine
      processing
- description: >-
    Binding of the essential cofactor pyridoxal 5'-phosphate (covalently bound to
    Lys209 as a Schiff base), required for AGT transaminase catalysis.
  molecular_function:
    id: GO:0030170
    label: pyridoxal phosphate binding
  locations:
  - id: GO:0005777
    label: peroxisome
  supported_by:
  - reference_id: PMID:17696873
    supporting_text: >-
      the G82E variant is able to bind 2 mol PLP/dimer
  - reference_id: PMID:20133649
    supporting_text: >-
      reduced coenzyme binding affinity
proposed_new_terms: []
suggested_questions:
- question: >-
    Beyond glyoxylate detoxification, how quantitatively important is the
    serine:pyruvate transaminase (SPT) activity of AGT to hepatic serine
    metabolism and gluconeogenesis in humans under physiological conditions?
- question: >-
    What is the identity of the proposed mammal-specific adaptor that enables the
    atypical KKL PTS1 of human AGT to be recognised by Pex5p?
suggested_experiments:
- description: >-
    Quantify in vivo flux through the glyoxylate->glycine (AGT) vs
    glyoxylate->oxalate (LDH) branches in human hepatocyte or liver-organoid
    models with wild-type vs PH1 mutant AGT, using stable-isotope-labelled
    glyoxylate.
- description: >-
    Systematically map AGT subcellular partitioning (peroxisome vs mitochondrion)
    across the panel of minor-allele PH1 mutations using quantitative
    immunofluorescence/fractionation, to test whether all minor-allele mutations
    unmask the cryptic mitochondrial targeting sequence.
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: file:human/AGXT/AGXT-uniprot.txt
  title: UniProtKB entry P21549 (AGT1_HUMAN), Alanine--glyoxylate aminotransferase
  findings: []
- id: PMID:10347152
  title: Flux of the L-serine metabolism in rabbit, human, and dog livers. Substantial
    contributions of both mitochondrial and peroxisomal serine:pyruvate/alanine:glyoxylate
    aminotransferase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; establishes AGT/SPT dual role in glyoxylate and serine
      metabolism and supports the EC 2.6.1.51 serine:pyruvate transaminase
      activity.
- id: PMID:10960483
  title: Functional synergism between the most common polymorphism in human alanine:glyoxylate
    aminotransferase and four of the most common disease-causing mutations.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; purified recombinant AGT is a folded, dimerized,
      catalytically active enzyme; documents cofactor and mistargeting biology.
- id: PMID:12777626
  title: 'Primary hyperoxaluria type 1 in the Canary Islands: a conformational disease
    due to I244T mutation in the P11L-containing alanine:glyoxylate aminotransferase.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified full text; AGXT*LTM colocalises with peroxisomal marker
      PMP70 and L11P/I244T causes loss of enzymatic activity.
- id: PMID:12899834
  title: Crystal structure of alanine:glyoxylate aminotransferase and the relationship
    between genotype and enzymatic phenotype in primary hyperoxaluria type 1.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; crystal structure of the AGT homodimer with PLP at Lys209
      and amino-oxyacetic acid inhibitor.
- id: PMID:15802217
  title: 'Overexpression of human alanine:glyoxylate aminotransferase in Escherichia
    coli: renaturation from guanidine-HCl and affinity for pyridoxal phosphate co-factor.'
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; determines KM for PLP by apoenzyme reconstitution,
      supporting the PLP-binding annotation.
- id: PMID:15911627
  title: Peroxisomal import of human alanine:glyoxylate aminotransferase requires
    ancillary targeting information remote from its C terminus.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; shows human AGT interacts with Pex5p and requires ancillary
      PTS1A targeting information (basis of the Pex5p IPI annotation).
- id: PMID:16971151
  title: 'Consequences of missense mutations for dimerization and turnover of alanine:glyoxylate
    aminotransferase: study of a spectrum of mutations.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; spectrum of PH1 missense mutations characterized for
      activity and dimerization (dimerization failure frequent).
- id: PMID:1703535
  title: Identification of mutations associated with peroxisome-to-mitochondrion mistargeting
    of alanine/glyoxylate aminotransferase in primary hyperoxaluria type 1.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; defines the P11L/G170R mistargeting biology and describes
      AGT as the normally peroxisomal enzyme.
- id: PMID:17696873
  title: 'Human wild-type alanine:glyoxylate aminotransferase and its naturally occurring
    G82E variant: functional properties and physiological implications.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; kinetic characterization concluding AGT is highly specific
      for glyoxylate-to-glycine processing; PLP binding (2 mol/dimer).
- id: PMID:18492492
  title: 'Reactions of human liver peroxisomal alanine:glyoxylate aminotransferase
    with beta-chloro-L-alanine and L-cysteine: spectroscopic and kinetic analysis.'
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; documents amino-acid (substrate) binding and in vitro
      L-cysteine side reactions (basis of the amino acid binding and L-cysteine
      catabolic annotations).
- id: PMID:20133649
  title: Molecular defects of the glycine 41 variants of alanine glyoxylate aminotransferase
    associated with primary hyperoxaluria type I.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; G41 variants increase the dimer-monomer dissociation
      constant and reduce coenzyme binding (supports homodimerization and PLP
      binding).
- id: PMID:22198249
  title: The N-terminal extension is essential for the formation of the active dimeric
    structure of liver peroxisomal alanine:glyoxylate aminotransferase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; N-terminal extension required for the active dimer;
      confirms peroxisomal targeting and PLP dependence.
- id: PMID:22529745
  title: Molecular requirements for peroxisomal targeting of alanine-glyoxylate aminotransferase
    as an essential determinant in primary hyperoxaluria type 1.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified full text; crystal structure of the Pex5p-(AGT)2-Pex5p
      cargo-receptor complex; basis of the PEX5 protein-binding IPI.
- id: PMID:23229545
  title: Four of the most common mutations in primary hyperoxaluria type 1 unmask
    the cryptic mitochondrial targeting sequence of alanine:glyoxylate aminotransferase
    encoded by the polymorphic minor allele.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified full text; establishes that failure to transaminate
      glyoxylate to glycine in peroxisomes lets glyoxylate be oxidised to oxalate.
- id: PMID:2363689
  title: 'Human peroxisomal L-alanine: glyoxylate aminotransferase. Evolutionary loss
    of a mitochondrial targeting signal by point mutation of the initiation codon.'
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; human AGT lost the ancestral mitochondrial targeting signal
      via an initiation-codon point mutation, explaining peroxisomal localization.
- id: PMID:24055001
  title: Gly161 mutations associated with Primary Hyperoxaluria Type I induce the
    cytosolic aggregation and the intracellular degradation of the apo-form of alanine:glyoxylate
    aminotransferase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; wild-type AGT is peroxisomal, Gly161 mutants aggregate in
      cytosol; supports peroxisome localization and catalytic activity.
- id: PMID:26149463
  title: Misfolding caused by the pathogenic mutation G47R on the minor allele of
    alanine:glyoxylate aminotransferase and chaperoning activity of pyridoxine.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; G47R-Mi is partly mistargeted to mitochondria and rescued
      to peroxisomes by pyridoxine; supports peroxisome localization and activity.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; proteome-scale HuRI Y2H map. AGXT protein-binding hits are
      mostly keratins/keratin-associated proteins with no established relationship
      to AGT function; over-annotated as bare protein binding.
- id: PMID:3418107
  title: 'Immunocytochemical localization of human hepatic alanine: glyoxylate aminotransferase
    in control subjects and patients with primary hyperoxaluria type 1.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; AGT confined to peroxisomes, randomly dispersed through the
      peroxisomal matrix (supports peroxisome/peroxisomal matrix).
- id: PMID:3709805
  title: Peroxisomal alanine:glyoxylate aminotransferase deficiency in primary hyperoxaluria
    type I.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; complete absence of peroxisomal AGT in PH1 liver; foundational
      for the peroxisomal enzyme deficiency model.
- id: PMID:7813517
  title: Evolution of alanine:glyoxylate aminotransferase 1 peroxisomal and mitochondrial
    targeting. A survey of its subcellular distribution in the livers of various representatives
    of the classes Mammalia, Aves and Amphibia.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; in human liver essentially all AGT is peroxisomal (type I),
      with species-dependent compartmentalization.
- id: PMID:9053548
  title: Immunocytochemical localization of peroxisomal proteins in human liver and
    kidney.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; methods paper localizing peroxisomal proteins including AGT
      in human liver.
- id: Reactome:R-HSA-389684
  title: glyoxylate + alanine => glycine + pyruvate [peroxisome]
  findings: []
- id: Reactome:R-HSA-9033235
  title: Cargo of PEX5S,L translocates from the cytosol to the peroxisomal matrix
  findings: []
- id: Reactome:R-HSA-9033236
  title: PEX5S,L:Cargo binds PEX13:PEX14:PEX2:PEX10:PEX12 (Docking and Translocation
    Module)
  findings: []