id: P60174
gene_symbol: TPI1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: Triosephosphate isomerase (TIM) is a cytosolic homodimeric enzyme (EC 5.3.1.1)
  that catalyzes the reversible interconversion of the two triose phosphates, dihydroxyacetone
  phosphate (DHAP) and D-glyceraldehyde-3-phosphate (G3P). By converting the DHAP produced
  by aldolase into G3P, it funnels both triose units into the payoff phase of glycolysis,
  effectively doubling the energetic yield of the pathway, and catalyzes the reverse
  reaction in gluconeogenesis. TIM is a textbook near-perfect, diffusion-limited catalyst
  built on the canonical (beta/alpha)8 TIM-barrel fold and is active only as a homodimer.
  It also suppresses the accumulation of the toxic side-product methylglyoxal, and displays
  a documented minor methylglyoxal-synthase-like activity that generates methylglyoxal from
  DHAP. Loss-of-function of TPI1 causes triosephosphate isomerase deficiency, a severe
  autosomal-recessive disorder featuring chronic hemolytic anemia and progressive
  neurodegeneration/neuromuscular dysfunction that is usually fatal in childhood; the most
  common allele (Glu104Asp) destabilizes the active dimer rather than abolishing catalysis.
alternative_products:
- name: '1'
  id: P60174-1
- name: '2'
  id: P60174-3
  sequence_note: VSP_060722
- name: '3'
  id: P60174-4
  sequence_note: VSP_060721
existing_annotations:
- term:
    id: GO:0004807
    label: triose-phosphate isomerase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Triose-phosphate isomerase activity (EC 5.3.1.1) is the defining, core
      molecular function of TPI1, phylogenetically conserved across the entire family
      and directly demonstrated for the human enzyme.
    action: ACCEPT
    reason: This is the core evolved function of the gene product. The IBA is well
      supported by the family-wide phylogenetic inference and confirmed for human TPI1
      by direct biochemistry and structure.
    supported_by:
      - reference_id: file:human/TPI1/TPI1-uniprot.txt
        supporting_text: "catalyzes the interconversion between dihydroxyacetone ...
          phosphate (DHAP) and D-glyceraldehyde-3-phosphate (G3P) in glycolysis ...
          and gluconeogenesis"
- term:
    id: GO:0006096
    label: glycolytic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: TPI1 acts in glycolysis, isomerizing DHAP (from the aldolase step) to
      G3P so that both triose units feed into the payoff phase of the pathway. This
      is a core biological process for the gene.
    action: ACCEPT
    reason: Glycolysis is one of the two central pathways the isomerase serves; strongly
      supported by phylogeny and by UniProt/Reactome pathway annotation.
    supported_by:
      - reference_id: file:human/TPI1/TPI1-uniprot.txt
        supporting_text: "Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-"
- term:
    id: GO:0006094
    label: gluconeogenesis
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: TPI1 also functions in gluconeogenesis, catalyzing the reverse (G3P to
      DHAP) reaction that supplies DHAP for fructose-1,6-bisphosphate synthesis. Core
      process.
    action: ACCEPT
    reason: Gluconeogenesis is the second central pathway served by the reversible
      isomerase; supported by phylogeny and UniProt pathway annotation.
    supported_by:
      - reference_id: file:human/TPI1/TPI1-uniprot.txt
        supporting_text: "Carbohydrate biosynthesis; gluconeogenesis"
- term:
    id: GO:0046166
    label: glyceraldehyde-3-phosphate biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: The TPI1 reaction produces D-glyceraldehyde-3-phosphate from DHAP; the
      UniProt/UniPathway description of the glycolytic step is the formation of
      G3P from glycerone phosphate.
    action: ACCEPT
    reason: A correct, more granular restatement of the isomerase's productive role
      in glycolysis (formation of G3P). Consistent with the core function; retained
      but subsidiary to the glycolytic-process/MF annotations.
    supported_by:
      - reference_id: file:human/TPI1/TPI1-uniprot.txt
        supporting_text: "glycolysis; D-glyceraldehyde 3-"
- term:
    id: GO:0004807
    label: triose-phosphate isomerase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic assertion of the core triose-phosphate isomerase activity
      (EC 5.3.1.1, RHEA:18585) via InterPro/ARBA. Redundant with the experimental
      and phylogenetic evidence but correct.
    action: ACCEPT
    reason: Correctly maps the TIM InterPro signatures and EC 5.3.1.1 to the core
      molecular function.
    supported_by:
      - reference_id: file:human/TPI1/TPI1-uniprot.txt
        supporting_text: "EC=5.3.1.1"
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: TPI1 is a cytoplasmic/cytosolic enzyme; UniProt Subcellular Location is
      Cytoplasm.
    action: ACCEPT
    reason: Correct localization derived from the UniProt Subcellular Location mapping;
      the more specific cytosol term is also annotated and is preferred for core function.
    supported_by:
      - reference_id: file:human/TPI1/TPI1-uniprot.txt
        supporting_text: "SUBCELLULAR LOCATION: Cytoplasm"
- term:
    id: GO:0006096
    label: glycolytic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Electronic assertion of the core glycolytic-process role via InterPro
      and UniPathway (UPA00109). Redundant with the IBA but correct.
    action: ACCEPT
    reason: Correctly captures TPI1's central role in glycolysis; consistent with the
      IBA and pathway annotations.
    supported_by:
      - reference_id: file:human/TPI1/TPI1-uniprot.txt
        supporting_text: "Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-"
- term:
    id: GO:0008929
    label: methylglyoxal synthase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: TPI1 has a documented minor methylglyoxal-synthase-like side activity
      (EC 4.2.3.3), generating the cytotoxic side-product methylglyoxal from DHAP.
      This is a genuine but non-core promiscuous activity, not the enzyme's evolved
      physiological function.
    action: KEEP_AS_NON_CORE
    reason: UniProt records the methylglyoxal-synthase activity (EC 4.2.3.3, RHEA:17937)
      as a secondary function responsible for "non-negligible" methylglyoxal production.
      It is real, so it is retained, but it is a promiscuous side reaction rather than
      the core triose-phosphate isomerase function and should not be treated as a core
      MF.
    supported_by:
      - reference_id: file:human/TPI1/TPI1-uniprot.txt
        supporting_text: "It is also responsible for the non-negligible production of ...
          methylglyoxal a reactive cytotoxic side-product"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20849852
  qualifier: enables
  review:
    summary: TPI1 was identified among six glycolytic enzymes co-purifying with
      cytoplasmic PCNA (P12004) in a Far-Western/mass-spectrometry screen. The bare
      "protein binding" term is uninformative and this interaction is peripheral to
      the enzyme's function.
    action: MARK_AS_OVER_ANNOTATED
    reason: GO:0005515 "protein binding" conveys no specific molecular function. The
      supporting paper is a proteomic interaction screen (PCNA-associated glycolytic
      enzymes) that does not establish a defined functional interaction for TPI1. Per
      curation policy the experimental IPI is retained (not removed) but flagged as an
      uninformative over-annotation.
    supported_by:
      - reference_id: PMID:20849852
        supporting_text: "PCNA is also associated with six glycolytic enzymes that are
          involved in the regulation of steps 4-9 in the glycolysis pathway"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21044950
  qualifier: enables
  review:
    summary: TPI1 (with TERF1/P54274) was flagged as a candidate telomere-protein
      interactor in a genome-wide split-YFP (BiFC) complementation screen. Bare
      "protein binding"; a high-throughput, transient-interaction screen not
      indicative of TPI1's core function.
    action: MARK_AS_OVER_ANNOTATED
    reason: GO:0005515 is uninformative, and the source is a large-scale complementation
      screen for telomere-interactome candidates in which many identified proteins were
      acknowledged as possible false positives. The experimental IPI is kept per policy
      but marked as an over-annotation.
    supported_by:
      - reference_id: PMID:21044950
        supporting_text: "we identified over 300 proteins that associated with the six
          core telomeric proteins"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: TPI1 (with huntingtin, HTT/P42858) appears as an edge in a large yeast
      two-hybrid neurodegenerative-disease interactome map. Bare "protein binding" from
      a systematic interactome screen; not a defined functional interaction.
    action: MARK_AS_OVER_ANNOTATED
    reason: GO:0005515 is uninformative and the evidence is a systematic Y2H/literature
      interactome connecting ~5,000 proteins via ~30,000 candidate interactions. The
      experimental IPI is retained per policy but flagged as an over-annotation.
    supported_by:
      - reference_id: PMID:32814053
        supporting_text: "connects ∼5,000 human proteins via ∼30,000 candidate
          interactions"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: is_active_in
  review:
    summary: Cytosol is the compartment where TPI1 carries out its glycolytic/gluconeogenic
      function. The is_active_in qualifier is appropriate for the site of the core activity.
    action: ACCEPT
    reason: Correct and specific location for the enzyme's core activity; transferred
      from the mouse ortholog and consistent with UniProt Cytoplasm localization.
    supported_by:
      - reference_id: file:human/TPI1/TPI1-uniprot.txt
        supporting_text: "SUBCELLULAR LOCATION: Cytoplasm"
- term:
    id: GO:0006094
    label: gluconeogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Electronic assertion (UniPathway UPA00138, ortholog transfer) of the core
      gluconeogenic role. Redundant with the IBA/Reactome annotations but correct.
    action: ACCEPT
    reason: Correctly captures TPI1's role in gluconeogenesis; consistent with the IBA
      and UniProt pathway annotation.
    supported_by:
      - reference_id: file:human/TPI1/TPI1-uniprot.txt
        supporting_text: "Carbohydrate biosynthesis; gluconeogenesis"
- term:
    id: GO:0016853
    label: isomerase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: The generic parent term isomerase activity is far too general for a
      well-characterized enzyme whose specific reaction (EC 5.3.1.1) is known.
    action: MODIFY
    reason: The enzyme's specific molecular function (EC 5.3.1.1) is known and directly
      annotated as GO:0004807. The generic parent term should be replaced by the
      specific child term.
    proposed_replacement_terms:
      - id: GO:0004807
        label: triose-phosphate isomerase activity
    supported_by:
      - reference_id: file:human/TPI1/TPI1-uniprot.txt
        supporting_text: "EC=5.3.1.1"
- term:
    id: GO:0019682
    label: glyceraldehyde-3-phosphate metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: TPI1 metabolizes G3P (interconverting it with DHAP); this term correctly
      but broadly describes that involvement.
    action: ACCEPT
    reason: A correct, if general, restatement of the isomerase's role in triose-phosphate
      metabolism; subsidiary to the glycolytic-process and MF annotations.
    supported_by:
      - reference_id: file:human/TPI1/TPI1-uniprot.txt
        supporting_text: "catalyzes the interconversion between dihydroxyacetone ...
          phosphate (DHAP) and D-glyceraldehyde-3-phosphate (G3P) in glycolysis"
- term:
    id: GO:0061621
    label: canonical glycolysis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Canonical glycolysis (the classical Embden-Meyerhof-Parnas pathway) is
      the specific glycolytic process TPI1 participates in. A precise child of glycolytic
      process.
    action: ACCEPT
    reason: Accurately places TPI1 in the canonical glycolytic pathway; more specific
      than, and consistent with, the glycolytic-process annotation.
    supported_by:
      - reference_id: file:human/TPI1/TPI1-uniprot.txt
        supporting_text: "Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-"
- term:
    id: GO:0006094
    label: gluconeogenesis
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-70263
  qualifier: involved_in
  review:
    summary: Reactome traceable assertion placing TPI1 in the gluconeogenesis pathway.
      Consistent with the core gluconeogenic role.
    action: ACCEPT
    reason: Authoritative pathway-database assertion of a core process for the gene.
- term:
    id: GO:0061621
    label: canonical glycolysis
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-70171
  qualifier: involved_in
  review:
    summary: Reactome traceable assertion placing TPI1 in the (canonical) glycolysis
      pathway. Consistent with the core glycolytic role.
    action: ACCEPT
    reason: Authoritative pathway-database assertion of a core process for the gene.
- term:
    id: GO:0004807
    label: triose-phosphate isomerase activity
  evidence_type: EXP
  original_reference_id: PMID:6434534
  qualifier: enables
  review:
    summary: Direct experimental study of purified human (placental) triosephosphate
      isomerase establishing the enzyme, its high specific activity, and its dimeric
      structure. Supports the core triose-phosphate isomerase activity.
    action: ACCEPT
    reason: Experimental characterization of the purified human enzyme (highest specific
      activity reported at the time), confirming the core molecular function.
    supported_by:
      - reference_id: PMID:6434534
        supporting_text: "Human placental triosephosphate isomerase was isolated by an
          improved procedure and recovered with the highest specific activity ever
          reported"
- term:
    id: GO:0008929
    label: methylglyoxal synthase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: Sequence-similarity transfer (from P00939) of the minor methylglyoxal-synthase-like
      side activity. Genuine but non-core promiscuous activity, duplicate of the IEA
      methylglyoxal synthase annotation.
    action: KEEP_AS_NON_CORE
    reason: Same minor side reaction (EC 4.2.3.3) as the IEA annotation; it is real but
      is a promiscuous side activity, not the enzyme's core function.
    supported_by:
      - reference_id: file:human/TPI1/TPI1-uniprot.txt
        supporting_text: "It is also responsible for the non-negligible production of ...
          methylglyoxal a reactive cytotoxic side-product"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-70454
  qualifier: located_in
  review:
    summary: Reactome localizes the TPI1-catalyzed reaction (DHAP to GA3P) to the cytosol.
      Correct core location.
    action: ACCEPT
    reason: Authoritative pathway-database assertion of the cytosolic site of the core
      isomerase reaction.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-70481
  qualifier: located_in
  review:
    summary: Reactome localizes the reverse TPI1 reaction (GA3P to DHAP) to the cytosol.
      Correct core location; duplicate of the preceding cytosol annotation.
    action: ACCEPT
    reason: Authoritative pathway-database assertion of the cytosolic site of the core
      isomerase reaction.
- term:
    id: GO:0019242
    label: methylglyoxal biosynthetic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: The process counterpart of the minor methylglyoxal-synthase side activity;
      TPI1 produces methylglyoxal as a cytotoxic side-product from DHAP. Non-core.
    action: KEEP_AS_NON_CORE
    reason: Corresponds to the promiscuous methylglyoxal-synthase side reaction, which
      is a genuine but minor/deleterious byproduct pathway rather than an evolved core
      biological process of TPI1.
    supported_by:
      - reference_id: file:human/TPI1/TPI1-uniprot.txt
        supporting_text: "It is also responsible for the non-negligible production of ...
          methylglyoxal a reactive cytotoxic side-product"
- term:
    id: GO:0046166
    label: glyceraldehyde-3-phosphate biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:18562316
  qualifier: involved_in
  review:
    summary: The structural/biochemical study of recombinant human TPI1 (WT and E104D)
      characterized the isomerase reaction that produces G3P. Supports the productive
      role in G3P formation. Subsidiary to glycolytic process / MF.
    action: ACCEPT
    reason: The paper directly assayed catalytic activity of purified recombinant human
      TPI1, supporting its role in producing D-glyceraldehyde-3-phosphate.
    supported_by:
      - reference_id: PMID:18562316
        supporting_text: "the purified, recombinant mutant enzyme E104D, while exhibiting
          normal catalytic activity"
- term:
    id: GO:0004807
    label: triose-phosphate isomerase activity
  evidence_type: IDA
  original_reference_id: PMID:18562316
  qualifier: enables
  review:
    summary: Direct assay of purified recombinant human TPI1 confirms the core
      triose-phosphate isomerase activity (with measured KM and Vmax reported in UniProt).
    action: ACCEPT
    reason: Experimental (IDA) confirmation of the core molecular function for the
      human enzyme; this is the anchor experimental evidence for EC 5.3.1.1.
    supported_by:
      - reference_id: PMID:18562316
        supporting_text: "the purified, recombinant mutant enzyme E104D, while exhibiting
          normal catalytic activity"
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:18562316
  qualifier: enables
  review:
    summary: TPI1 is an obligate homodimer, and the active dimer is required for full
      function; this study directly showed the E104D disease mutant is impaired in
      forming active dimers. Homodimerization is integral to the enzyme's core activity.
    action: ACCEPT
    reason: Directly demonstrated homodimerization and its functional importance (the
      most common disease mutation acts by destabilizing the dimer). Retained as a
      core structural aspect of the isomerase's molecular function.
    supported_by:
      - reference_id: PMID:18562316
        supporting_text: "shows impairments in the formation of active dimers and low
          thermostability and monomerizes under conditions in which the wild type
          retains its dimeric form"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23355646
  qualifier: enables
  review:
    summary: TPI1 was identified among sperm-head proteins in a screen for zona-pellucida
      binding partners (a putative moonlighting role). Bare "protein binding"; the paper
      itself frames these glycolytic enzymes as multifaceted/moonlighting rather than
      as a defined interaction.
    action: MARK_AS_OVER_ANNOTATED
    reason: GO:0005515 is uninformative, and the supporting evidence is a proteomic
      sperm-protein screen describing possible moonlighting functions, not a specific
      characterized molecular interaction of TPI1. The experimental IPI is retained per
      policy but marked as an over-annotation.
    supported_by:
      - reference_id: PMID:23355646
        supporting_text: "Their multiple roles ... suggest that these sperm proteins are
          multifaceted or moonlighting proteins"
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: IPI
  original_reference_id: PMID:19725078
  qualifier: enables
  review:
    summary: TPI1 co-purified with the E3 ubiquitin-protein ligase Parkin (PARK2/O60260)
      in a tandem-affinity-purification/MS proteomics screen, alongside many mitochondrial
      and glycolytic proteins. A peripheral interactome finding, not a core function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The evidence is a Parkin-interactome proteomics screen in which TPI1 is one
      of many glycolytic/energy-metabolism proteins recovered; this does not establish a
      characterized, functionally meaningful ubiquitin-ligase-binding activity for TPI1.
      Retained per policy but flagged as an over-annotation.
    supported_by:
      - reference_id: PMID:19725078
        supporting_text: "Nine of these are directly involved in mitochondrial energy
          metabolism and glycolysis"
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:23533145
  qualifier: located_in
  review:
    summary: TPI1 was detected by shotgun proteomics of exosomes from expressed prostatic
      secretions in urine. A high-throughput MS detection consistent with the common
      presence of abundant cytosolic glycolytic enzymes in exosomes; not the site of the
      core function.
    action: KEEP_AS_NON_CORE
    reason: Valid high-throughput proteomic detection, but exosomal localization is a
      secondary/moonlighting or passive-packaging observation rather than where TPI1
      performs its core glycolytic function.
    supported_by:
      - reference_id: PMID:23533145
        supporting_text: "exosome preparations were characterized by a shotgun proteomics
          procedure"
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: HDA
  original_reference_id: PMID:16502470
  qualifier: located_in
  review:
    summary: TPI1 was among low-abundance proteins detected in the aqueous phase of human
      colostrum by proteomics. An extracellular-fluid MS detection, not the core cytosolic
      site of function.
    action: KEEP_AS_NON_CORE
    reason: Valid proteomic detection in a body fluid; extracellular presence is secondary
      and does not reflect the enzyme's core intracellular glycolytic function.
    supported_by:
      - reference_id: PMID:16502470
        supporting_text: "investigated the low abundance proteins in the aqueous phase of
          human colostrum"
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: HDA
  original_reference_id: PMID:21630459
  qualifier: located_in
  review:
    summary: TPI1 was detected in a proteomic catalogue of the human sperm nucleus (403
      proteins). A high-throughput detection; likely cytoplasmic carryover or a specialized
      moonlighting context rather than a general nuclear function of TPI1.
    action: KEEP_AS_NON_CORE
    reason: Valid MS detection in isolated sperm nuclei, but nuclear localization is not
      part of TPI1's core glycolytic function and may reflect a cell-type-specific or
      contaminating signal. Retained as non-core.
    supported_by:
      - reference_id: PMID:21630459
        supporting_text: "403 different proteins have been identified from the isolated
          sperm nuclei"
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: HDA
  original_reference_id: PMID:22664934
  qualifier: located_in
  review:
    summary: TPI (TPI1) was among proteins identified in human tear fluid in a breast-cancer
      biomarker proteomics study. An extracellular-fluid detection, not the core site of
      function.
    action: KEEP_AS_NON_CORE
    reason: Valid proteomic detection in tears; extracellular presence is secondary and
      does not reflect the enzyme's core intracellular function.
    supported_by:
      - reference_id: PMID:22664934
        supporting_text: "different metabolic cascades (ALDH3A or ... TPI)"
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: HDA
  original_reference_id: PMID:23580065
  qualifier: located_in
  review:
    summary: TPI1 was among proteins detected in a shotgun-proteomics analysis of tears
      from glaucoma patients. Extracellular-fluid MS detection; not the core site of
      function. Duplicate extracellular-region evidence.
    action: KEEP_AS_NON_CORE
    reason: Valid proteomic detection in a body fluid; extracellular presence is secondary
      to the core intracellular glycolytic function.
    supported_by:
      - reference_id: PMID:23580065
        supporting_text: "shotgun proteomics approach to tears of patients with POAG"
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19056867
  qualifier: located_in
  review:
    summary: TPI1 was detected in a large-scale proteomic profile of human urinary
      exosomes. High-throughput MS detection consistent with exosomal packaging of
      abundant cytosolic enzymes; not the core site of function. Duplicate exosome
      evidence.
    action: KEEP_AS_NON_CORE
    reason: Valid proteomic detection in exosomes, but this localization is secondary and
      does not reflect where TPI1 performs its core glycolytic function.
    supported_by:
      - reference_id: PMID:19056867
        supporting_text: "used LC-MS/MS to profile the proteome of human urinary exosomes"
- term:
    id: GO:0004807
    label: triose-phosphate isomerase activity
  evidence_type: TAS
  original_reference_id: PMID:2579079
  qualifier: enables
  review:
    summary: Early cloning/protein-structure study of human triosephosphate isomerase
      (and TPI deficiency), supporting the core isomerase molecular function.
    action: ACCEPT
    reason: Traceable assertion of the core enzyme identity/function from a foundational
      human TPI cDNA and protein-structure paper; redundant with the experimental IDA
      but correct.
    supported_by:
      - reference_id: PMID:2579079
        supporting_text: "Nine cDNA clones of human adult liver triosephosphate (TP)
          isomerase have been isolated and characterized"
- term:
    id: GO:0004807
    label: triose-phosphate isomerase activity
  evidence_type: NAS
  original_reference_id: PMID:2876430
  qualifier: enables
  review:
    summary: Study of the Glu104Asp TPI-deficiency mutation, defining TPI as
      D-glyceraldehyde-3-phosphate ketol-isomerase (EC 5.3.1.1). Non-traceable author
      statement of the core molecular function.
    action: ACCEPT
    reason: Correctly asserts the core triose-phosphate isomerase identity/function of
      the gene; consistent with all experimental evidence. Redundant with the IDA/EXP
      annotations but not wrong.
    supported_by:
      - reference_id: PMID:2876430
        supporting_text: "Triose-phosphate isomerase (TPI; D-glyceraldehyde-3-phosphate
          ketol-isomerase, EC 5.3.1.1)"
core_functions:
- description: Triose-phosphate isomerase activity — the reversible, near-diffusion-limited
    interconversion of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde-3-phosphate
    (G3P) (EC 5.3.1.1) — carried out by the cytosolic homodimeric enzyme in glycolysis
    and gluconeogenesis.
  molecular_function:
    id: GO:0004807
    label: triose-phosphate isomerase activity
  directly_involved_in:
    - id: GO:0006096
      label: glycolytic process
    - id: GO:0006094
      label: gluconeogenesis
  locations:
    - id: GO:0005829
      label: cytosol
  supported_by:
    - reference_id: PMID:18562316
      supporting_text: "the purified, recombinant mutant enzyme E104D, while exhibiting
        normal catalytic activity"
    - reference_id: file:human/TPI1/TPI1-uniprot.txt
      supporting_text: "catalyzes the interconversion between dihydroxyacetone ...
        phosphate (DHAP) and D-glyceraldehyde-3-phosphate (G3P) in glycolysis ...
        and gluconeogenesis"
references:
- id: file:human/TPI1/TPI1-uniprot.txt
  title: UniProtKB P60174 (TPIS_HUMAN) entry for human triosephosphate isomerase
  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: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: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:16502470
  title: 'Human colostrum: identification of minor proteins in the aqueous phase by
    proteomics.'
  findings: []
- id: PMID:18562316
  title: 'Structural basis of human triosephosphate isomerase deficiency: mutation
    E104D is related to alterations of a conserved water network at the dimer interface.'
  findings: []
- id: PMID:19056867
  title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
  findings: []
- id: PMID:19725078
  title: Proteomic analysis of increased Parkin expression and its interactants provides
    evidence for a role in modulation of mitochondrial function.
  findings: []
- id: PMID:20849852
  title: Proliferating cell nuclear antigen in the cytoplasm interacts with components
    of glycolysis and cancer.
  findings: []
- id: PMID:21044950
  title: Genome-wide YFP fluorescence complementation screen identifies new regulators
    for telomere signaling in human cells.
  findings: []
- id: PMID:21630459
  title: Proteomic characterization of the human sperm nucleus.
  findings: []
- id: PMID:22664934
  title: Comparison of tear protein levels in breast cancer patients and healthy controls
    using a de novo proteomic approach.
  findings: []
- id: PMID:23355646
  title: Identification of sperm head proteins involved in zona pellucida binding.
  findings: []
- id: PMID:23533145
  title: In-depth proteomic analyses of exosomes isolated from expressed prostatic
    secretions in urine.
  findings: []
- id: PMID:23580065
  title: Shotgun proteomics reveals specific modulated protein patterns in tears of
    patients with primary open angle glaucoma naïve to therapy.
  findings: []
- id: PMID:2579079
  title: Human triosephosphate isomerase cDNA and protein structure. Studies of triosephosphate
    isomerase deficiency in man.
  findings: []
- id: PMID:2876430
  title: 'Human triose-phosphate isomerase deficiency: a single amino acid substitution
    results in a thermolabile enzyme.'
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
- id: PMID:6434534
  title: Primary structure of human triosephosphate isomerase.
  findings: []
- id: Reactome:R-HSA-70171
  title: Glycolysis
  findings: []
- id: Reactome:R-HSA-70263
  title: Gluconeogenesis
  findings: []
- id: Reactome:R-HSA-70454
  title: TPI1 dimer isomerizes DHAP to GA3P
  findings: []
- id: Reactome:R-HSA-70481
  title: TPI1 dimer isomerizes GA3P to DHAP
  findings: []