id: Q00266
gene_symbol: MAT1A
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  MAT1A encodes the alpha-1 catalytic subunit of the liver-specific methionine
  adenosyltransferase (S-adenosylmethionine synthase isoform type-1; EC 2.5.1.6),
  which assembles into the MAT I homotetramer and the MAT III homodimer. The enzyme
  catalyses S-adenosyl-L-methionine (SAM/AdoMet) synthesis from L-methionine and ATP
  (L-methionine + ATP + H2O -> S-adenosyl-L-methionine + phosphate + diphosphate) in an
  unusual two-step reaction that cleaves both ends of the ATP triphosphate chain, requiring
  Mg2+ and K+. SAM is the universal methyl donor for most cellular transmethylation
  reactions and the committed entry point of the methionine/SAM cycle. MAT1A is a cytosolic
  enzyme expressed predominantly in adult liver, where the bulk of SAM is produced.
  Loss-of-function variants cause methionine adenosyltransferase I/III deficiency (MATD;
  isolated persistent hypermethioninemia): usually clinically benign, but severe biallelic
  forms produce hepatic SAM deficiency and central-nervous-system demyelination.
existing_annotations:
- term:
    id: GO:0004478
    label: methionine adenosyltransferase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Phylogenetic (IBA) call of the core catalytic molecular function. MAT1A is the
      liver alpha-1 subunit of methionine adenosyltransferase and directly synthesizes SAM
      from L-methionine and ATP. This is the defining activity of the gene and is corroborated
      by direct enzyme assays and structural work.
    action: ACCEPT
    reason: >-
      Correct and central molecular function, consistent across the AdoMet synthase family
      and confirmed experimentally for human MAT1A.
    supported_by:
    - reference_id: file:human/MAT1A/MAT1A-uniprot.txt
      supporting_text: "Reaction=L-methionine + ATP + H2O = S-adenosyl-L-methionine + phosphate"
    - reference_id: PMID:23425511
      supporting_text: >-
        MAT catalyses the transfer of the adenosyl group from ATP to the sulfur atom of Met
        (L-methionine), in an unusual two-step reaction cleaving at both ends of the ATP
        triphosphate chain
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetic (IBA) localization to the cytosol. MAT1A is a soluble cytosolic enzyme;
      SAM synthesis occurs in the cytoplasm and there are no membrane, signal, or organellar
      targeting features in the UniProt record.
    action: ACCEPT
    reason: >-
      Correct subcellular location, consistent with the family and with Reactome TAS
      annotations to the same term.
    supported_by:
    - reference_id: PMID:10677294
      supporting_text: >-
        The MAT1A gene is expressed primarily in the liver, the organ in which synthesis of
        the predominant portion of AdoMet occurs
- term:
    id: GO:0006556
    label: S-adenosylmethionine biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Phylogenetic (IBA) call of the core biological process: SAM biosynthesis. This is the
      process directly executed by the MAT catalytic activity and is the single-step pathway
      "S-adenosyl-L-methionine from L-methionine" in UniProt.
    action: ACCEPT
    reason: >-
      Directly reflects the enzyme's committed catalytic role in producing the universal
      methyl donor; well supported experimentally.
    supported_by:
    - reference_id: PMID:23425511
      supporting_text: >-
        MAT constitutes the first reaction step of the essential ‘methionine cycle’
- term:
    id: GO:0004478
    label: methionine adenosyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Electronic (ARBA/InterPro, mapped to RHEA:21080 / EC 2.5.1.6) assignment of the core
      methionine adenosyltransferase activity. Duplicates the IBA and IDA calls for the same
      correct molecular function.
    action: ACCEPT
    reason: >-
      Correct catalytic function; the InterPro/RHEA/EC mapping matches the experimentally
      demonstrated activity.
    supported_by:
    - reference_id: file:human/MAT1A/MAT1A-uniprot.txt
      supporting_text: "EC=2.5.1.6 {ECO:0000269|PubMed:10677294}"
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro-based electronic annotation of ATP binding. ATP is a co-substrate of the MAT
      reaction and the crystal structures resolve multiple ATP-binding residues, so the term
      is correct, though it is a sub-feature of the catalytic activity rather than a distinct
      core function.
    action: ACCEPT
    reason: >-
      True molecular activity (ATP is a substrate; UniProt lists numerous ATP-binding
      residues), but non-core: it is subsumed by the methionine adenosyltransferase activity.
    supported_by:
    - reference_id: file:human/MAT1A/MAT1A-uniprot.txt
      supporting_text: "Reaction=L-methionine + ATP + H2O = S-adenosyl-L-methionine + phosphate"
- term:
    id: GO:0006556
    label: S-adenosylmethionine biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: >-
      Electronic (ARBA/InterPro/UniPathway) assignment of the SAM biosynthetic process,
      duplicating the IBA and IDA annotations for this core process.
    action: ACCEPT
    reason: >-
      Correct process, matching the UniPathway "S-adenosyl-L-methionine from L-methionine"
      pathway and the experimental IDA/IMP evidence.
    supported_by:
    - reference_id: PMID:25075345
      supporting_text: >-
        which is synthesized by methionine adenosyltransferase (MAT), is the main source of
        methyl groups
- term:
    id: GO:0051259
    label: protein complex oligomerization
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      Electronic (ARBA) annotation of generic protein complex oligomerization. MAT1A does
      oligomerize (MAT I homotetramer, MAT III homodimer), but a more specific and
      experimentally supported term, protein homotetramerization (GO:0051289), is already
      annotated by IDA.
    action: MODIFY
    reason: >-
      The essence is correct but the term is too general; the specific homo-oligomerization
      of identical subunits is better captured by GO:0051289 protein homotetramerization,
      which is directly supported by the crystal structure.
    proposed_replacement_terms:
    - id: GO:0051289
      label: protein homotetramerization
    supported_by:
    - reference_id: file:human/MAT1A/MAT1A-uniprot.txt
      supporting_text: "Homotetramer (MAT-I); dimer of dimers (PubMed:23425511)"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: >-
      IntAct/BioPlex 2.0 high-throughput affinity-purification mass-spectrometry interactome
      screen; the WITH/FROM records the MAT1A-MAT2A (P31153) association. The bare
      "protein binding" term is uninformative about the molecular function of MAT1A.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative generic protein-binding term derived from a proteome-scale screen; per
      curation guidelines bare "protein binding" is not retained as a core function. Kept
      (not removed) because it is an experimental IPI.
    supported_by:
    - reference_id: PMID:28514442
      supporting_text: >-
        uses robust affinity purification-mass spectrometry methodology to elucidate protein
        interaction networks and co-complexes nucleated by more than 25% of protein-coding
        genes from the human genome
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: >-
      IntAct/HuRI binary (yeast two-hybrid) interactome map; WITH/FROM records the
      MAT1A-MAT2A (P31153) interaction. Bare "protein binding" is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic protein-binding term from a proteome-scale binary interactome; not retained as
      a core molecular function per curation guidelines. Kept as an experimental IPI.
    supported_by:
    - reference_id: PMID:32296183
      supporting_text: A reference map of the human binary protein interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: >-
      IntAct neurodegenerative-disease interactome screen; WITH/FROM records interactions
      with APP (P05067) and HTT (P42858). These are screen-derived associations, not an
      informative molecular function of MAT1A.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Bare "protein binding" from a high-throughput interactome study; uninformative as a
      molecular function. Kept as an experimental IPI rather than removed.
    supported_by:
    - reference_id: PMID:32814053
      supporting_text: >-
        Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and
        Uncovers Widespread Protein Aggregation in Affected Brains.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: >-
      IntAct/BioPlex 3.0 affinity-purification mass-spectrometry interactome; WITH/FROM
      records the MAT1A-MAT2A (P31153) association. Bare "protein binding" is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic protein-binding term from a proteome-scale AP-MS network; not a core molecular
      function per curation guidelines. Kept as an experimental IPI.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: >-
        Through affinity-purification mass spectrometry, we have created two proteome-scale,
        cell-line-specific interaction networks.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: >-
      IntAct multimodal cell-map (AP-MS/imaging) study; WITH/FROM records the MAT1A-MAT2A
      (P31153) association. Bare "protein binding" is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic protein-binding term from a systems-scale interactome/cell-map study; not
      retained as a core molecular function. Kept as an experimental IPI.
    supported_by:
    - reference_id: PMID:40205054
      supporting_text: Multimodal cell maps as a foundation for structural and functional genomics.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: >-
      IntAct/CCSB interactome mapping; WITH/FROM records a MAT1A-MAT1A (Q00266) self
      interaction. This self-association reflects the genuine biology of the enzyme, which
      forms the MAT I homotetramer and MAT III homodimer of identical alpha-1 subunits.
    action: ACCEPT
    reason: >-
      Unlike bare "protein binding", identical protein binding is informative here: MAT1A is
      an obligate homo-oligomer (homotetramer/homodimer), so self-association is a real
      functional property. The self-interaction WITH/FROM (Q00266) is consistent with the
      crystal structure and UniProt SUBUNIT annotation.
    supported_by:
    - reference_id: PMID:10677294
      supporting_text: >-
        MAT I and MAT III are homotetramers and homodimers of the
    - reference_id: file:human/MAT1A/MAT1A-uniprot.txt
      supporting_text: "Homotetramer (MAT-I); dimer of dimers (PubMed:23425511)"
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: >-
      IntAct/HuRI binary interactome; self (Q00266) interaction. Reflects MAT1A
      homo-oligomerization into MAT I (tetramer) and MAT III (dimer).
    action: ACCEPT
    reason: >-
      Informative and biologically correct: MAT1A self-association underlies the functional
      MAT I/III oligomers, consistent with structural and enzymatic evidence.
    supported_by:
    - reference_id: file:human/MAT1A/MAT1A-uniprot.txt
      supporting_text: "Homotetramer (MAT-I); dimer of dimers (PubMed:23425511)"
- term:
    id: GO:0048269
    label: methionine adenosyltransferase complex
  evidence_type: IPI
  original_reference_id: PMID:37917677
  qualifier: part_of
  review:
    summary: >-
      ComplexPortal assignment of MAT1A as a subunit of the methionine adenosyltransferase
      complex (the homomeric MAT I/III complex, CPX-3168/CPX-3169). The functional MAT1A
      enzyme is an oligomeric complex of alpha-1 subunits.
    action: ACCEPT
    reason: >-
      MAT1A is only catalytically functional as an oligomeric MAT complex (homotetramer MAT I
      / homodimer MAT III), so part_of the methionine adenosyltransferase complex is correct.
      PMID:37917677 studies the MAT1A enzyme (the terminal enzyme of SAM biosynthesis) and its
      isoform-specific Cys120.
    supported_by:
    - reference_id: PMID:37917677
      supporting_text: >-
        S-adenosylmethionine synthase isoform type-1 (MAT1A), the terminal enzyme in SAM
        biosynthesis, at a privileged, isoform-specific Cys120
    - reference_id: file:human/MAT1A/MAT1A-uniprot.txt
      supporting_text: "Homotetramer (MAT-I); dimer of dimers (PubMed:23425511)"
- term:
    id: GO:0006556
    label: S-adenosylmethionine biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:25075345
  qualifier: involved_in
  review:
    summary: >-
      ComplexPortal IDA (direct assay) for the SAM biosynthetic process. This structure/
      function study characterizes the ATP-driven synthesis of SAM by methionine
      adenosyltransferase enzymes, including demonstration that a MAT1A-containing complex
      (MAT(alpha1)4(betaV1)2) is stable in vitro.
    action: ACCEPT
    reason: >-
      Directly supports the core SAM-biosynthesis process for the MAT enzymes; MAT1A is the
      liver catalytic subunit executing this reaction.
    supported_by:
    - reference_id: PMID:25075345
      supporting_text: >-
        S-adenosylmethionine (SAMe) is the principal methyl donor of the cell and is
    - reference_id: PMID:25075345
      supporting_text: "the complex MAT(α1)4(βV1)2 is stable in vitro"
- term:
    id: GO:0048269
    label: methionine adenosyltransferase complex
  evidence_type: IPI
  original_reference_id: PMID:25075345
  qualifier: part_of
  review:
    summary: >-
      ComplexPortal assignment of MAT1A to the methionine adenosyltransferase complex, based
      on the structural characterization of MAT complexes. MAT1A (alpha-1) forms the
      homo-oligomeric MAT I/III complex and, in vitro, a MAT(alpha1)4(betaV1)2 assembly.
    action: ACCEPT
    reason: >-
      Correct: MAT1A functions as part of an oligomeric methionine adenosyltransferase
      complex. This paper explicitly shows the MAT1A (alpha1)-containing complex is stable.
    supported_by:
    - reference_id: PMID:25075345
      supporting_text: "the complex MAT(α1)4(βV1)2 is stable in vitro"
- term:
    id: GO:0004478
    label: methionine adenosyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:10677294
  qualifier: enables
  review:
    summary: >-
      Direct assay (IDA) of methionine adenosyltransferase activity. Chamberlin et al.
      characterized MATD missense variants by transient-expression enzyme assays, measuring
      residual MAT activity relative to wild type (e.g. R264C has virtually no activity,
      G336R retains 23%), directly demonstrating the catalytic function of MAT1A.
    action: ACCEPT
    reason: >-
      Experimental demonstration of the core catalytic activity in human MAT1A; the enzyme
      catalyses the two-step transfer of the adenosyl moiety of ATP to methionine to form
      AdoMet.
    supported_by:
    - reference_id: PMID:10677294
      supporting_text: >-
        catalyzes an unusual two-step reaction that involves the transfer of the adenosyl
        moiety of ATP to methionine to form
    - reference_id: PMID:10677294
      supporting_text: R264C has virtually no enzymatic activity
- term:
    id: GO:0006556
    label: S-adenosylmethionine biosynthetic process
  evidence_type: IMP
  original_reference_id: PMID:10677294
  qualifier: involved_in
  review:
    summary: >-
      Mutant-phenotype (IMP) evidence for involvement in SAM biosynthesis: loss-of-function
      MAT1A variants abolish or greatly reduce MAT I/III activity and cause hepatic AdoMet
      synthesis deficiency (isolated hypermethioninemia), establishing the gene's role in the
      SAM biosynthetic process.
    action: ACCEPT
    reason: >-
      Human genetic (variant) evidence directly ties MAT1A to SAM biosynthesis, the core
      process for this gene.
    supported_by:
    - reference_id: PMID:10677294
      supporting_text: >-
        The MAT1A gene is expressed primarily in the liver, the organ in which synthesis of
        the predominant portion of AdoMet occurs
- term:
    id: GO:0009087
    label: L-methionine catabolic process
  evidence_type: IMP
  original_reference_id: PMID:10677294
  qualifier: involved_in
  review:
    summary: >-
      Mutant-phenotype (IMP) evidence: deleterious MAT1A variants cause abnormal accumulation
      of methionine (hypermethioninemia), because the SAM-synthesis reaction is the principal
      route of methionine consumption in the liver. In this sense MAT1A contributes to
      L-methionine catabolism/disposal via SAM formation.
    action: KEEP_AS_NON_CORE
    reason: >-
      Defensible: the MAT reaction consumes L-methionine, and its loss causes methionine to
      accumulate, so MAT1A participates in methionine catabolism. However, the gene's core
      framing is SAM biosynthesis (methionine is the substrate), so methionine catabolism is
      a downstream/related process rather than the primary function.
    supported_by:
    - reference_id: PMID:10677294
      supporting_text: >-
        is characterized by persistent hypermethioninemia without
    - reference_id: PMID:10677294
      supporting_text: >-
        Current evidence establishes that deleterious MAT1A mutations cause abnormal
        accumulation of methionine
- term:
    id: GO:0051289
    label: protein homotetramerization
  evidence_type: IDA
  original_reference_id: PMID:23425511
  qualifier: involved_in
  review:
    summary: >-
      Direct (crystallographic) evidence that MAT1A assembles as a homotetramer (MAT I),
      described as a dimer of dimers, with the SAM-bound human MAT1A structure (PDB 2OBV).
    action: ACCEPT
    reason: >-
      Experimentally demonstrated homo-oligomerization; MAT I is a homotetramer of the MAT1A
      alpha-1 subunit, and MAT III a homodimer. This is the specific, well-supported
      oligomerization term.
    supported_by:
    - reference_id: PMID:23425511
      supporting_text: organizes into tetramer (isoform I) or dimer (isoform III)
    - reference_id: file:human/MAT1A/MAT1A-uniprot.txt
      supporting_text: "Homotetramer (MAT-I); dimer of dimers (PubMed:23425511)"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5603087
  qualifier: located_in
  review:
    summary: >-
      Reactome traceable-author-statement localization to the cytosol (reaction: defective
      MAT1A does not transfer Ado from ATP to L-Met). Consistent with the cytosolic
      IBA annotation.
    action: ACCEPT
    reason: >-
      Correct cytosolic localization; MAT1A is a soluble cytoplasmic enzyme.
    supported_by:
    - reference_id: PMID:10677294
      supporting_text: >-
        The MAT1A gene is expressed primarily in the liver, the organ in which synthesis of
        the predominant portion of AdoMet occurs
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-174391
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS localization to the cytosol (reaction: MAT1A multimers transfer Ado from
      ATP to L-Met). Duplicates the cytosol annotation for the SAM-synthesis reaction.
    action: ACCEPT
    reason: >-
      Correct cytosolic localization of the SAM-synthesis reaction catalysed by MAT1A
      multimers.
    supported_by:
    - reference_id: PMID:23425511
      supporting_text: organizes into tetramer (isoform I) or dimer (isoform III)
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2408551
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS localization to the cytosol (reaction: SeMet is converted to AdoSeMet by
      MAT). Reflects the cytosolic MAT activity acting on the selenomethionine analogue.
    action: ACCEPT
    reason: >-
      Correct cytosolic localization; MAT can also adenosylate selenomethionine in the
      cytosol.
    supported_by:
    - reference_id: PMID:10677294
      supporting_text: >-
        The MAT1A gene is expressed primarily in the liver, the organ in which synthesis of
        the predominant portion of AdoMet occurs
core_functions:
- description: >-
    Catalyses synthesis of S-adenosyl-L-methionine (SAM/AdoMet), the universal cellular methyl
    donor, from L-methionine and ATP in the cytosol of hepatocytes; the committed first step of
    the methionine/SAM cycle.
  molecular_function:
    id: GO:0004478
    label: methionine adenosyltransferase activity
  directly_involved_in:
  - id: GO:0006556
    label: S-adenosylmethionine biosynthetic process
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/MAT1A/MAT1A-uniprot.txt
    supporting_text: "Reaction=L-methionine + ATP + H2O = S-adenosyl-L-methionine + phosphate"
  - reference_id: PMID:23425511
    supporting_text: >-
      MAT constitutes the first reaction step of the essential ‘methionine cycle’
- description: >-
    Assembles as a homo-oligomer (MAT I homotetramer / MAT III homodimer) of identical alpha-1
    subunits, forming the functional cytosolic methionine adenosyltransferase complex required
    for SAM synthesis.
  molecular_function:
    id: GO:0042802
    label: identical protein binding
  directly_involved_in:
  - id: GO:0051289
    label: protein homotetramerization
  locations:
  - id: GO:0005829
    label: cytosol
  in_complex:
    id: GO:0048269
    label: methionine adenosyltransferase complex
  supported_by:
  - reference_id: PMID:23425511
    supporting_text: organizes into tetramer (isoform I) or dimer (isoform III)
  - reference_id: file:human/MAT1A/MAT1A-uniprot.txt
    supporting_text: "Homotetramer (MAT-I); dimer of dimers (PubMed:23425511)"
proposed_new_terms: []
suggested_questions:
- question: >-
    Beyond forming the catalytic MAT I/III oligomers, does MAT1A have any physiologically
    relevant heteromeric partners in adult hepatocytes, or are its reported protein-binding
    interactions (e.g. with MAT2A, APP, HTT) artefacts of proteome-scale screens?
- question: >-
    How does isoform-specific regulation of the MAT1A Cys120 gating-loop residue
    (S-nitrosylation and formaldehyde adduction) modulate hepatic SAM levels in vivo?
suggested_experiments:
- description: >-
    Quantitative in vitro kinetics (Km, Vmax) of recombinant human MAT I vs MAT III on
    L-methionine and ATP, with Mg2+/K+ dependence, to define the catalytic parameters distinct
    from the ubiquitous MAT2A isoform.
- description: >-
    Targeted metabolomics of hepatic SAM, SAH, and methionine in MAT1A-variant hepatocytes to
    correlate residual enzyme activity with methylation-potential (SAM/SAH ratio) and the
    clinical spectrum of MATD.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  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/MAT1A/MAT1A-uniprot.txt
  title: UniProtKB Q00266 (METK1_HUMAN) S-adenosylmethionine synthase isoform type-1
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Curated UniProt record; catalytic activity, cofactors, subunit structure, tissue
      specificity, disease, and PTMs used to ground the review.
- id: PMID:10677294
  title: 'Methionine adenosyltransferase I/III deficiency: novel mutations and clinical
    variations.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Primary paper for MAT1A catalytic activity (IDA), SAM biosynthesis / methionine
      catabolism (IMP), and the MATD disease phenotype; full text available.
- id: PMID:23425511
  title: Insight into S-adenosylmethionine biosynthesis from the crystal structures
    of the human methionine adenosyltransferase catalytic and regulatory subunits.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Crystal structure of human MAT1A bound to SAM (PDB 2OBV); establishes homotetramer/
      dimer architecture and the two-step catalytic mechanism.
- id: PMID:25075345
  title: Structure and function study of the complex that synthesizes S-adenosylmethionine.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Focuses on the MATalpha2beta complex but characterizes MAT catalytic function and shows
      a MAT1A (alpha1)-containing complex is stable in vitro; ComplexPortal used it for the
      MAT complex / SAM-biosynthesis annotations.
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Proteome-scale interactome screen; source of a MAT1A self (identical protein binding)
      interaction consistent with homo-oligomerization.
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      BioPlex 2.0 AP-MS screen; source of a generic protein-binding IPI (MAT1A-MAT2A);
      uninformative for MAT1A molecular function.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      HuRI binary (Y2H) interactome; source of both a generic protein-binding IPI and a
      self (identical protein binding) IPI.
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Neurodegeneration interactome screen; source of generic protein-binding IPIs
      (MAT1A-APP, MAT1A-HTT); abstract-only cache; uninformative for MAT1A function.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      BioPlex 3.0 AP-MS screen; source of a generic protein-binding IPI (MAT1A-MAT2A).
- id: PMID:37917677
  title: Formaldehyde regulates S-adenosylmethionine biosynthesis and one-carbon metabolism.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Identifies MAT1A as the terminal enzyme in SAM biosynthesis and its isoform-specific
      Cys120 as a formaldehyde-reactive regulatory site; used by ComplexPortal for MAT complex
      membership.
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Systems-scale multimodal cell-map study; source of a generic protein-binding IPI
      (MAT1A-MAT2A).
- id: Reactome:R-HSA-174391
  title: MAT1A multimers transfer Ado from ATP to L-Met
  findings: []
- id: Reactome:R-HSA-2408551
  title: SeMet is converted to AdoSeMet by MAT
  findings: []
- id: Reactome:R-HSA-5603087
  title: Defective MAT1A does not transfer Ado from ATP to L-Met
  findings: []