id: P29401
gene_symbol: TKT
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  TKT encodes transketolase (EC 2.2.1.1), a thiamine-diphosphate (TPP/ThDP)- and
  divalent-cation (Mg2+; also Ca2+/Mn2+/Co2+)-dependent enzyme of the non-oxidative
  branch of the pentose phosphate pathway. It reversibly transfers a two-carbon
  glycolaldehyde (ketol) unit from a ketose donor to an aldose acceptor via a covalent
  ThDP intermediate, interconverting sugar phosphates. It catalyses
  xylulose-5-phosphate + ribose-5-phosphate <-> sedoheptulose-7-phosphate +
  glyceraldehyde-3-phosphate, and xylulose-5-phosphate + erythrose-4-phosphate <->
  fructose-6-phosphate + glyceraldehyde-3-phosphate, thereby linking the pentose
  phosphate pathway to glycolysis and balancing the cell's supply of ribose-5-phosphate
  (for nucleotide synthesis) against NADPH regeneration. The active enzyme is a
  cytosolic homodimer with two active sites at the dimer interface, each binding one
  ThDP and one divalent metal ion. Erythrocyte transketolase activity is a classic
  clinical index of thiamine (vitamin B1) status. Autosomal-recessive transketolase
  deficiency causes a syndrome of short stature, developmental delay, and congenital
  heart defects.
alternative_products:
- name: '1'
  id: P29401-1
- name: '2'
  id: P29401-2
  sequence_note: VSP_045566
existing_annotations:
- term:
    id: GO:0004802
    label: transketolase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Transketolase activity is the defining molecular function of TKT, supported by
      biochemistry, kinetics, crystal structures with substrates, and disease genetics.
      IBA phylogenetic inference is fully concordant with direct experimental evidence.
    action: ACCEPT
    reason: >-
      TKT is the canonical human transketolase (EC 2.2.1.1); the two-carbon ketol
      transfer activity is directly demonstrated crystallographically and kinetically.
    supported_by:
    - reference_id: PMID:20667822
      supporting_text: >-
        The crystal structure of human transketolase (TKT), a thiamine diphosphate
        (ThDP) and Ca(2+)-dependent enzyme that catalyzes the interketol transfer between
        ketoses and aldoses as part of the pentose phosphate pathway
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Transketolase is a cytosolic enzyme; IBA localization is consistent with the
      pentose phosphate pathway operating in the cytosol and with Reactome TAS
      cytosol annotations.
    action: ACCEPT
    reason: >-
      The non-oxidative PPP is a cytosolic process and the human enzyme acts in the
      cytosol; this is the appropriate active-in location for the core function.
    supported_by:
    - reference_id: PMID:20667822
      supporting_text: >-
        catalyzes the interketol transfer between ketoses and aldoses as part of the
        pentose phosphate pathway
- term:
    id: GO:0009052
    label: pentose-phosphate shunt, non-oxidative branch
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      TKT operates in the non-oxidative branch of the pentose phosphate pathway,
      interconverting pentose and hexose/triose phosphates. This is the correct,
      specific biological-process term for the core function.
    action: ACCEPT
    reason: >-
      Both experimental (patient metabolite profiles) and structural work place TKT
      squarely in the non-oxidative PPP; IBA is at the right level of specificity.
    supported_by:
    - reference_id: PMID:27259054
      supporting_text: >-
        Transketolase deficiency is one of a growing list of inborn errors of
        metabolism in the non-oxidative part of the pentose phosphate
- term:
    id: GO:0030976
    label: thiamine pyrophosphate binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      TKT binds thiamine diphosphate (thiamine pyrophosphate) as an essential catalytic
      cofactor, one ThDP per subunit, as shown biochemically and in numerous crystal
      structures. IBA is concordant with direct evidence.
    action: ACCEPT
    reason: >-
      ThDP binding is a core, mechanistically required molecular function of
      transketolase; the covalent ThDP intermediate mediates two-carbon transfer.
    supported_by:
    - reference_id: PMID:9357955
      supporting_text: >-
        Active human transketolase is a homodimeric enzyme possessing two active sites
- term:
    id: GO:0004802
    label: transketolase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Electronic assignment of transketolase activity via EC 2.2.1.1 / RHEA:10508 and
      ortholog mapping. Redundant with, and confirmed by, the experimental IDA/EXP and
      IBA transketolase-activity annotations.
    action: ACCEPT
    reason: >-
      The IEA mapping is correct and matches the demonstrated catalytic activity.
    supported_by:
    - reference_id: PMID:20667822
      supporting_text: >-
        The crystal structure of human transketolase (TKT), a thiamine diphosphate
        (ThDP) and Ca(2+)-dependent enzyme that catalyzes the interketol transfer between
        ketoses and aldoses as part of the pentose phosphate pathway
- term:
    id: GO:0016744
    label: transketolase or transaldolase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    summary: >-
      ARBA grouping term covering both transketolase and transaldolase activity. TKT is
      specifically a transketolase, so the more specific GO:0004802 already captures the
      activity; this grouping term is less precise.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The disjunctive "transketolase or transaldolase activity" term is less informative
      than the demonstrated transketolase activity (GO:0004802). It is not wrong but is
      an over-general ARBA-derived assignment superseded by the specific term.
    supported_by:
    - reference_id: PMID:20667822
      supporting_text: >-
        catalyzes the interketol transfer between ketoses and aldoses as part of the
        pentose phosphate pathway
- term:
    id: GO:0019682
    label: glyceraldehyde-3-phosphate metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      Glyceraldehyde-3-phosphate is a product/substrate of the transketolase reactions,
      so TKT does participate in G3P metabolism, but this is a downstream consequence of
      its non-oxidative PPP role rather than a distinct core function.
    action: KEEP_AS_NON_CORE
    reason: >-
      G3P metabolism is a general process term that follows from transketolase activity
      linking the PPP to glycolysis; correct but peripheral to the core PPP role.
    supported_by:
    - reference_id: PMID:20667822
      supporting_text: >-
        catalyzes the interketol transfer between ketoses and aldoses as part of the
        pentose phosphate pathway
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21044950
  qualifier: enables
  review:
    summary: >-
      Bare "protein binding" from a high-throughput genome-wide YFP fluorescence
      complementation telomere-interactome screen, reporting an interaction with
      TERF1/TRF1 (UniProtKB:P54274). The term is uninformative about TKT's molecular
      function and the interaction is not characterized as functionally meaningful for
      transketolase.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Per curation guidelines, bare protein binding conveys no functional information.
      The single high-throughput interaction (with a telomeric protein) has no
      established biological role for TKT and is not a core molecular function.
    supported_by:
    - reference_id: PMID:21044950
      supporting_text: >-
        Maintenance of vertebrate telomeres requires the concerted action of members of
        the Telomere Interactome, built upon the six core telomeric proteins TRF1, TRF2,
        RAP1, TIN2, TPP1, and POT1
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: is_active_in
  review:
    summary: >-
      Electronic (Ensembl Compara ortholog) assignment of cytosolic localization,
      redundant with and confirmed by the IBA and Reactome TAS cytosol annotations.
    action: ACCEPT
    reason: >-
      Cytosol is the correct active-in location for transketolase.
    supported_by:
    - reference_id: PMID:20667822
      supporting_text: >-
        catalyzes the interketol transfer between ketoses and aldoses as part of the
        pentose phosphate pathway
- term:
    id: GO:0006098
    label: pentose-phosphate shunt
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Correct but general PPP term. TKT specifically acts in the non-oxidative branch
      (GO:0009052), so the parent term is retained as non-core context.
    action: KEEP_AS_NON_CORE
    reason: >-
      Parent of the more specific non-oxidative-branch term that better represents the
      core function; not wrong, but superseded by GO:0009052 for the core role.
    supported_by:
    - reference_id: PMID:27259054
      supporting_text: >-
        inborn errors of metabolism in the non-oxidative part of the pentose phosphate
- term:
    id: GO:0009052
    label: pentose-phosphate shunt, non-oxidative branch
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Electronic (Ensembl Compara) assignment of the non-oxidative PPP branch, redundant
      with and confirmed by the IBA and NAS annotations to the same term.
    action: ACCEPT
    reason: >-
      Correct and at the appropriate level of specificity for TKT's core process.
    supported_by:
    - reference_id: PMID:27259054
      supporting_text: >-
        Transketolase deficiency is one of a growing list of inborn errors of
        metabolism in the non-oxidative part of the pentose phosphate
- term:
    id: GO:1901159
    label: D-xylulose 5-phosphate biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      D-xylulose-5-phosphate is a product of the reversible transketolase reactions, so
      TKT contributes to its biosynthesis, but this is one metabolite of the broader
      non-oxidative PPP interconversion rather than a distinct core function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct as a downstream consequence of transketolase activity (the reactions are
      reversible and interconvert several sugar phosphates); peripheral to the core PPP
      role.
    supported_by:
    - reference_id: PMID:20667822
      supporting_text: >-
        catalyzes the interketol transfer between ketoses and aldoses as part of the
        pentose phosphate pathway
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: >-
      HPA high-throughput immunofluorescence localization to the nucleoplasm. TKT is
      an abundant cytosolic PPP enzyme; nucleoplasmic signal likely reflects diffuse
      distribution or possible moonlighting rather than a core catalytic location.
    action: KEEP_AS_NON_CORE
    reason: >-
      Not the site of the core transketolase function; retained as a non-core
      localization observation from immunofluorescence-based curation.
    supported_by:
    - reference_id: GO_REF:0000052
      supporting_text: Gene Ontology annotation based on curation of immunofluorescence data
- term:
    id: GO:0016604
    label: nuclear body
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: >-
      HPA immunofluorescence localization to nuclear bodies. As with the other nuclear
      annotations, this is not the site of the core cytosolic transketolase function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Non-core localization from high-throughput immunofluorescence; peripheral to
      transketolase's PPP function.
    supported_by:
    - reference_id: GO_REF:0000052
      supporting_text: Gene Ontology annotation based on curation of immunofluorescence data
- term:
    id: GO:0016607
    label: nuclear speck
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: >-
      HPA immunofluorescence localization to nuclear speckles. Not the site of the core
      cytosolic transketolase function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Non-core localization from high-throughput immunofluorescence; peripheral to
      transketolase's PPP function.
    supported_by:
    - reference_id: GO_REF:0000052
      supporting_text: Gene Ontology annotation based on curation of immunofluorescence data
- term:
    id: GO:0004802
    label: transketolase activity
  evidence_type: EXP
  original_reference_id: PMID:27259054
  qualifier: enables
  review:
    summary: >-
      Direct experimental confirmation of transketolase activity: enzymatic testing of
      patients with biallelic TKT variants showed significantly reduced transketolase
      activity, and disease results from transketolase deficiency.
    action: ACCEPT
    reason: >-
      Strong experimental support (patient enzymology plus recombinant catalytic-activity
      assays); this is the core molecular function.
    supported_by:
    - reference_id: PMID:27259054
      supporting_text: >-
        Enzymatic testing confirmed significantly reduced transketolase
    - reference_id: PMID:27259054
      supporting_text: >-
        an autosomal-recessively inherited deficiency of transketolase, encoded by TKT,
        on chromosome 3p21
- term:
    id: GO:0000287
    label: magnesium ion binding
  evidence_type: IDA
  original_reference_id: PMID:9611778
  qualifier: enables
  review:
    summary: >-
      Transketolase requires Mg2+ as a cofactor that anchors ThDP; recombinant human
      enzyme shows defined Km for Mg2+, and D155 mutation abolishes ThDP-Mg binding.
      One Mg2+ per subunit is the physiological divalent cofactor.
    action: ACCEPT
    reason: >-
      Mg2+ binding is a core, mechanistically required molecular function (metal-assisted
      ThDP cofactor binding), directly demonstrated biochemically and structurally.
    supported_by:
    - reference_id: PMID:9611778
      supporting_text: >-
        the K(m) values for thiamin diphosphate and for Mg2+ were, respectively, 4.1 +/-
        0.8 and 2.5 +/- 0.4 microM
    - reference_id: PMID:9357955
      supporting_text: >-
        aspartate 155 is an important
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IDA
  original_reference_id: PMID:20667822
  qualifier: enables
  review:
    summary: >-
      Ca2+ was resolved in the divalent-cation site of the human transketolase crystal
      structure. This is the same metal site that physiologically binds Mg2+; Ca2+ is a
      crystallization/substitute cation rather than the biological cofactor (UniProt
      lists Mg2+ as the cofactor, with Ca2+/Mn2+/Co2+ as alternatives).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      "Calcium ion binding" reflects the metal observed in a crystal structure at the
      cofactor site, not a distinct physiological calcium-binding function. The core
      divalent-cation function is better captured by magnesium ion binding (GO:0000287).
    supported_by:
    - reference_id: PMID:20667822
      supporting_text: >-
        The crystal structure of human transketolase (TKT), a thiamine diphosphate
        (ThDP) and Ca(2+)-dependent enzyme
- term:
    id: GO:0006098
    label: pentose-phosphate shunt
  evidence_type: IDA
  original_reference_id: PMID:20667822
  qualifier: involved_in
  review:
    summary: >-
      Direct evidence places transketolase in the pentose phosphate pathway. The general
      "pentose-phosphate shunt" term is correct; the non-oxidative branch (GO:0009052)
      is the more specific representation of the core process.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct but general parent term; retained as context, with GO:0009052 carrying the
      core, more specific process role.
    supported_by:
    - reference_id: PMID:20667822
      supporting_text: >-
        catalyzes the interketol transfer between ketoses and aldoses as part of the
        pentose phosphate pathway
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:23533145
  qualifier: located_in
  review:
    summary: >-
      TKT was detected in a large-scale shotgun proteomic survey of prostatic-secretion
      urinary exosomes (~900 proteins). Abundant cytosolic metabolic enzymes are
      routinely co-isolated in such exosome proteomes; this does not indicate a bona fide
      extracellular/exosomal function for transketolase.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput exosome-proteome detection of an abundant cytosolic enzyme; not a
      functional localization for the core PPP role.
    supported_by:
    - reference_id: PMID:23533145
      supporting_text: >-
        In pooled EPS-urine exosome samples, ~900 proteins were detected
- term:
    id: GO:0031982
    label: vesicle
  evidence_type: HDA
  original_reference_id: PMID:19190083
  qualifier: located_in
  review:
    summary: >-
      TKT was identified among cytoplasmic enzymes in exosome-like vesicles from human
      tracheobronchial epithelium proteomics. The authors themselves note metabolic
      enzymes are incorporated during intracellular vesicle formation; this is not a
      functional vesicular localization.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput vesicle-proteome detection of an abundant cytosolic enzyme; not a
      core localization.
    supported_by:
    - reference_id: PMID:19190083
      supporting_text: >-
        The presence of enzymes involved in intracellular metabolism ( i.e .,
        dehydrogenases, kinases, transferases, and enolase) inside the vesicular lumen
        suggest their inward invagination during intracellular formation
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19056867
  qualifier: located_in
  review:
    summary: >-
      TKT was detected in a large-scale proteomic profile of normal human urinary
      exosomes (1132 proteins). As above, co-isolation of an abundant cytosolic enzyme in
      exosome proteomics is not evidence of a bona fide exosomal function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput exosome-proteome detection; not a functional localization for
      transketolase.
    supported_by:
    - reference_id: PMID:19056867
      supporting_text: >-
        the analysis identified 1132 proteins unambiguously
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:20458337
  qualifier: located_in
  review:
    summary: >-
      TKT was among 539 proteins identified in a proteomic analysis of purified B-cell
      exosomes. Detection of an abundant cytosolic metabolic enzyme in an exosome
      proteome is not evidence of a functional exosomal localization.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput exosome-proteome detection; not a core localization for the PPP
      function.
    supported_by:
    - reference_id: PMID:20458337
      supporting_text: >-
        identified 539 proteins
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-163741
  qualifier: located_in
  review:
    summary: >-
      Reactome traceable assertion placing the transketolase reaction (G3P +
      sedoheptulose-7-P <-> xylulose-5-P + ribose-5-P) in the cytosol. Consistent with
      the cytosolic non-oxidative PPP.
    action: ACCEPT
    reason: >-
      Correct cytosolic localization for the core function, from a curated pathway
      reaction.
    supported_by:
    - reference_id: PMID:20667822
      supporting_text: >-
        catalyzes the interketol transfer between ketoses and aldoses as part of the
        pentose phosphate pathway
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-163751
  qualifier: located_in
  review:
    summary: >-
      Reactome traceable assertion placing the transketolase reaction (G3P + fructose-6-P
      <-> xylulose-5-P + erythrose-4-P) in the cytosol. Consistent with the cytosolic
      non-oxidative PPP.
    action: ACCEPT
    reason: >-
      Correct cytosolic localization for the core function, from a curated pathway
      reaction.
    supported_by:
    - reference_id: PMID:20667822
      supporting_text: >-
        catalyzes the interketol transfer between ketoses and aldoses as part of the
        pentose phosphate pathway
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-71324
  qualifier: located_in
  review:
    summary: >-
      Reactome traceable assertion placing the transketolase reaction (ribose-5-P +
      xylulose-5-P <-> sedoheptulose-7-P + G3P) in the cytosol. Consistent with the
      cytosolic non-oxidative PPP.
    action: ACCEPT
    reason: >-
      Correct cytosolic localization for the core function, from a curated pathway
      reaction.
    supported_by:
    - reference_id: PMID:20667822
      supporting_text: >-
        catalyzes the interketol transfer between ketoses and aldoses as part of the
        pentose phosphate pathway
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-71335
  qualifier: located_in
  review:
    summary: >-
      Reactome traceable assertion placing the transketolase reaction (xylulose-5-P +
      erythrose-4-P <-> G3P + fructose-6-P) in the cytosol. Consistent with the cytosolic
      non-oxidative PPP.
    action: ACCEPT
    reason: >-
      Correct cytosolic localization for the core function, from a curated pathway
      reaction.
    supported_by:
    - reference_id: PMID:20667822
      supporting_text: >-
        catalyzes the interketol transfer between ketoses and aldoses as part of the
        pentose phosphate pathway
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9761852
  qualifier: located_in
  review:
    summary: >-
      Reactome traceable assertion (NFE2L2-dependent TKT gene expression context) placing
      TKT in the cytosol. Consistent with the cytosolic localization of the enzyme.
    action: ACCEPT
    reason: >-
      Correct cytosolic localization for the core function.
    supported_by:
    - reference_id: PMID:20667822
      supporting_text: >-
        catalyzes the interketol transfer between ketoses and aldoses as part of the
        pentose phosphate pathway
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: >-
      Peroxisomal localization transferred by sequence similarity from the yeast ortholog
      (UniProtKB:P50137). Human/mammalian transketolase is a cytosolic enzyme and the
      human protein carries no recognized peroxisomal targeting signal; the yeast
      peroxisomal association does not transfer to human TKT.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      ISS transfer from a yeast ortholog is not supported for the human protein, which
      operates in the cytosol; peroxisomal localization is an over-annotation.
    supported_by:
    - reference_id: PMID:20667822
      supporting_text: >-
        catalyzes the interketol transfer between ketoses and aldoses as part of the
        pentose phosphate pathway
- term:
    id: GO:0009052
    label: pentose-phosphate shunt, non-oxidative branch
  evidence_type: NAS
  original_reference_id: PMID:9357955
  qualifier: involved_in
  review:
    summary: >-
      Non-oxidative PPP branch assignment based on author statement. Concordant with the
      IBA and IEA annotations to the same specific term; TKT's core process.
    action: ACCEPT
    reason: >-
      Correct and specific process term for transketolase's core role.
    supported_by:
    - reference_id: PMID:9357955
      supporting_text: >-
        Active human transketolase is a homodimeric enzyme possessing two active sites
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:20667822
  qualifier: enables
  review:
    summary: >-
      The active enzyme is an obligate homodimer, with two active sites formed at the
      dimer interface, as shown crystallographically. Homodimerization is required for
      the functional enzyme.
    action: ACCEPT
    reason: >-
      Homodimerization is directly demonstrated and functionally required (each active
      site is built at the dimer interface); a genuine, well-supported molecular function.
    supported_by:
    - reference_id: PMID:20667822
      supporting_text: >-
        Two monomers
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:9357955
  qualifier: enables
  review:
    summary: >-
      Independent evidence that active transketolase is a homodimer and that cofactor
      (ThDP-Mg) binding is required for dimer formation.
    action: ACCEPT
    reason: >-
      Directly demonstrated homodimerization coupled to cofactor binding; functionally
      required assembly.
    supported_by:
    - reference_id: PMID:9357955
      supporting_text: >-
        Active human transketolase is a homodimeric enzyme possessing two active sites
- term:
    id: GO:0004802
    label: transketolase activity
  evidence_type: IDA
  original_reference_id: PMID:20667822
  qualifier: enables
  review:
    summary: >-
      Direct crystallographic and kinetic characterization of human transketolase
      activity, including steady-state kinetics and NMR-based intermediate analysis of
      the donor half-reaction.
    action: ACCEPT
    reason: >-
      Direct experimental demonstration of the core catalytic activity.
    supported_by:
    - reference_id: PMID:20667822
      supporting_text: >-
        The crystal structure of human transketolase (TKT), a thiamine diphosphate
        (ThDP) and Ca(2+)-dependent enzyme that catalyzes the interketol transfer between
        ketoses and aldoses as part of the pentose phosphate pathway
- term:
    id: GO:0004802
    label: transketolase activity
  evidence_type: IDA
  original_reference_id: PMID:8419340
  qualifier: enables
  review:
    summary: >-
      Cloning and characterization of human transketolase cDNAs; establishes the gene as
      a single-copy gene encoding transketolase, in the context of Wernicke-Korsakoff
      syndrome and thiamine (TPP) affinity.
    action: ACCEPT
    reason: >-
      Supports the identity and transketolase activity of the TKT gene product.
    supported_by:
    - reference_id: PMID:8419340
      supporting_text: >-
        Transketolase was found to be a single copy gene which produces a single mRNA of
        approximately 2100 nucleotides
- term:
    id: GO:0004802
    label: transketolase activity
  evidence_type: IDA
  original_reference_id: PMID:9357955
  qualifier: enables
  review:
    summary: >-
      Characterization of recombinant human transketolase, including cofactor-dependent
      hysteresis and the D155 mutation that abolishes activity by preventing ThDP-Mg
      binding and dimerization.
    action: ACCEPT
    reason: >-
      Direct experimental characterization of transketolase activity and its cofactor
      requirements.
    supported_by:
    - reference_id: PMID:9357955
      supporting_text: >-
        aspartate 155 is an important
- term:
    id: GO:0004802
    label: transketolase activity
  evidence_type: IDA
  original_reference_id: PMID:9611778
  qualifier: enables
  review:
    summary: >-
      Heterologous expression of human transketolase with measured specific activity and
      Km values for D-xylulose-5-phosphate and D-ribose-5-phosphate, matching the native
      erythrocyte enzyme.
    action: ACCEPT
    reason: >-
      Direct enzymatic demonstration of transketolase activity with kinetic parameters.
    supported_by:
    - reference_id: PMID:9611778
      supporting_text: >-
        the K(m) values were 0.27 +/- 0.02 and 0.51 +/- 0.05 mM for the substrates
        D-xylulose 5-phosphate and D-ribose 5-phosphate
- term:
    id: GO:0046166
    label: glyceraldehyde-3-phosphate biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:9611778
  qualifier: involved_in
  review:
    summary: >-
      Glyceraldehyde-3-phosphate is produced by the transketolase reactions, so TKT
      participates in G3P biosynthesis. This follows from the core transketolase activity
      linking the PPP to glycolysis, rather than being a separate core function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct downstream consequence of transketolase catalysis (the reactions produce
      G3P); peripheral to the core non-oxidative PPP role.
    supported_by:
    - reference_id: PMID:9611778
      supporting_text: >-
        the K(m) values were 0.27 +/- 0.02 and 0.51 +/- 0.05 mM for the substrates
        D-xylulose 5-phosphate and D-ribose 5-phosphate
core_functions:
- description: >-
    Transketolase: TPP/Mg2+-dependent transfer of a two-carbon glycolaldehyde (ketol)
    unit between sugar phosphates in the cytosolic non-oxidative branch of the pentose
    phosphate pathway, interconverting pentose, hexose and triose phosphates and linking
    the PPP to glycolysis.
  molecular_function:
    id: GO:0004802
    label: transketolase activity
  directly_involved_in:
  - id: GO:0009052
    label: pentose-phosphate shunt, non-oxidative branch
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:20667822
    supporting_text: >-
      The crystal structure of human transketolase (TKT), a thiamine diphosphate
      (ThDP) and Ca(2+)-dependent enzyme that catalyzes the interketol transfer between
      ketoses and aldoses as part of the pentose phosphate pathway
  - reference_id: PMID:27259054
    supporting_text: >-
      Transketolase deficiency is one of a growing list of inborn errors of metabolism
      in the non-oxidative part of the pentose phosphate
- description: >-
    Binds thiamine diphosphate (thiamine pyrophosphate), one per subunit, as the
    essential catalytic cofactor that forms the covalent reaction intermediate for
    two-carbon transfer.
  molecular_function:
    id: GO:0030976
    label: thiamine pyrophosphate binding
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:9357955
    supporting_text: >-
      Active human transketolase is a homodimeric enzyme possessing two active sites
- description: >-
    Binds a divalent metal ion (physiologically Mg2+), one per subunit, that anchors the
    diphosphate of ThDP in the active site and is required for cofactor binding and dimer
    assembly.
  molecular_function:
    id: GO:0000287
    label: magnesium ion binding
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:9611778
    supporting_text: >-
      the K(m) values for thiamin diphosphate and for Mg2+ were, respectively, 4.1 +/-
      0.8 and 2.5 +/- 0.4 microM
  - reference_id: PMID:9357955
    supporting_text: >-
      aspartate 155 is an important
proposed_new_terms: []
suggested_questions:
- question: >-
    Does the nucleoplasmic/nuclear-speckle localization observed by HPA reflect a genuine
    moonlighting role for transketolase, or diffuse antibody signal?
- question: >-
    To what extent do the erythrocyte transketolase activation coefficient and TKT protein
    level track thiamine status quantitatively across tissues?
suggested_experiments:
- description: >-
    Confirm subcellular localization of endogenous TKT by fractionation and validated
    antibodies / tagged knock-in to test the reported nuclear signal.
- description: >-
    Structure-function assays of SDDHD patient variants (e.g. the 18-bp in-frame insertion
    and the missense variant) to quantify effects on catalysis, ThDP/Mg binding, and
    dimerization.
references:
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  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: PMID:19056867
  title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Large-scale urinary exosome proteomics; TKT is an incidental co-isolated cytosolic
      enzyme, not a functional exosomal localization.
- id: PMID:19190083
  title: 'Characterization of exosome-like vesicles released from human tracheobronchial
    ciliated epithelium: a possible role in innate defense.'
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Vesicle proteomics; supports incidental presence of cytosolic metabolic enzymes in
      vesicle lumen, not a functional vesicular role for TKT.
- id: PMID:20458337
  title: MHC class II-associated proteins in B-cell exosomes and potential functional
    implications for exosome biogenesis.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      B-cell exosome proteome (539 proteins); TKT incidental, not a functional
      localization.
- id: PMID:20667822
  title: The crystal structure of human transketolase and new insights into its mode
    of action.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Definitive human TKT crystal structure with ThDP and divalent cation; establishes
      catalytic activity, homodimer, cofactor binding and kinetics.
- id: PMID:21044950
  title: Genome-wide YFP fluorescence complementation screen identifies new regulators
    for telomere signaling in human cells.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      High-throughput telomere-interactome YFP complementation screen; source of the
      uninformative TKT-TERF1 protein-binding IPI, no established functional relevance.
- id: PMID:23533145
  title: In-depth proteomic analyses of exosomes isolated from expressed prostatic
    secretions in urine.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Prostatic-secretion urinary exosome proteomics (~900 proteins); TKT incidental
      co-isolation.
- id: PMID:27259054
  title: Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental
    Delay, and Congenital Heart Defects.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Establishes autosomal-recessive transketolase deficiency (SDDHD) with reduced
      enzyme activity in patients; in-vivo confirmation of TKT function in the
      non-oxidative PPP.
- id: PMID:8419340
  title: Cloning of human transketolase cDNAs and comparison of the nucleotide sequence
    of the coding region in Wernicke-Korsakoff and non-Wernicke-Korsakoff individuals.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Cloning of human TKT cDNA; single-copy gene; Wernicke-Korsakoff/thiamine context.
- id: PMID:9357955
  title: Aspartate 155 of human transketolase is essential for thiamine diphosphate-magnesium
    binding, and cofactor binding is required for dimer formation.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Homodimer with two active sites, non-covalent ThDP+Mg per site; D155 essential for
      cofactor-Mg binding and dimerization.
- id: PMID:9611778
  title: Heterologous expression of human transketolase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Recombinant human TKT with Km for xylulose-5-P/ribose-5-P and for ThDP/Mg2+;
      matches native erythrocyte enzyme.
- id: Reactome:R-HSA-163741
  title: 'D-glyceraldehyde 3-phosphate + sedoheptulose 7-phosphate<=> xylulose 5-phosphate+ribose
    5-phosphate '
  findings: []
- id: Reactome:R-HSA-163751
  title: D-glyceraldehyde 3-phosphate + D-fructose 6-phosphate   <=> xylulose 5-phosphate
    + D-erythrose 4-phosphate
  findings: []
- id: Reactome:R-HSA-71324
  title: ribose 5-phosphate + xylulose 5-phosphate <=> sedoheptulose 7-phosphate +
    D-glyceraldehyde 3-phosphate
  findings: []
- id: Reactome:R-HSA-71335
  title: xylulose 5-phosphate + D-erythrose 4-phosphate <=> D-glyceraldehyde 3-phosphate
    + D-fructose 6-phosphate
  findings: []
- id: Reactome:R-HSA-9761852
  title: NFE2L2-dependent TKT gene expression
  findings: []