TKT

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004802 transketolase activity	IBA GO_REF:0000033	ACCEPT	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. Reason: TKT is the canonical human transketolase (EC 2.2.1.1); the two-carbon ketol transfer activity is directly demonstrated crystallographically and kinetically. Supporting Evidence: PMID:20667822 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
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	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. 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. Supporting Evidence: PMID:20667822 catalyzes the interketol transfer between ketoses and aldoses as part of the pentose phosphate pathway
GO:0009052 pentose-phosphate shunt, non-oxidative branch	IBA GO_REF:0000033	ACCEPT	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. 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. Supporting Evidence: PMID:27259054 Transketolase deficiency is one of a growing list of inborn errors of metabolism in the non-oxidative part of the pentose phosphate
GO:0030976 thiamine pyrophosphate binding	IBA GO_REF:0000033	ACCEPT	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. Reason: ThDP binding is a core, mechanistically required molecular function of transketolase; the covalent ThDP intermediate mediates two-carbon transfer. Supporting Evidence: PMID:9357955 Active human transketolase is a homodimeric enzyme possessing two active sites
GO:0004802 transketolase activity	IEA GO_REF:0000120	ACCEPT	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. Reason: The IEA mapping is correct and matches the demonstrated catalytic activity. Supporting Evidence: PMID:20667822 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
GO:0016744 transketolase or transaldolase activity	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	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. 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. Supporting Evidence: PMID:20667822 catalyzes the interketol transfer between ketoses and aldoses as part of the pentose phosphate pathway
GO:0019682 glyceraldehyde-3-phosphate metabolic process	IEA GO_REF:0000117	KEEP AS NON CORE	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. 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. Supporting Evidence: PMID:20667822 catalyzes the interketol transfer between ketoses and aldoses as part of the pentose phosphate pathway
GO:0005515 protein binding	IPI PMID:21044950 Genome-wide YFP fluorescence complementation screen identifi...	MARK AS OVER ANNOTATED	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. 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. Supporting Evidence: PMID:21044950 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
GO:0005829 cytosol	IEA GO_REF:0000107	ACCEPT	Summary: Electronic (Ensembl Compara ortholog) assignment of cytosolic localization, redundant with and confirmed by the IBA and Reactome TAS cytosol annotations. Reason: Cytosol is the correct active-in location for transketolase. Supporting Evidence: PMID:20667822 catalyzes the interketol transfer between ketoses and aldoses as part of the pentose phosphate pathway
GO:0006098 pentose-phosphate shunt	IEA GO_REF:0000107	KEEP AS NON CORE	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. 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. Supporting Evidence: PMID:27259054 inborn errors of metabolism in the non-oxidative part of the pentose phosphate
GO:0009052 pentose-phosphate shunt, non-oxidative branch	IEA GO_REF:0000107	ACCEPT	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. Reason: Correct and at the appropriate level of specificity for TKT's core process. Supporting Evidence: PMID:27259054 Transketolase deficiency is one of a growing list of inborn errors of metabolism in the non-oxidative part of the pentose phosphate
GO:1901159 D-xylulose 5-phosphate biosynthetic process	IEA GO_REF:0000107	KEEP AS NON CORE	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. Reason: Correct as a downstream consequence of transketolase activity (the reactions are reversible and interconvert several sugar phosphates); peripheral to the core PPP role. Supporting Evidence: PMID:20667822 catalyzes the interketol transfer between ketoses and aldoses as part of the pentose phosphate pathway
GO:0005654 nucleoplasm	IDA GO_REF:0000052	KEEP AS NON CORE	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. Reason: Not the site of the core transketolase function; retained as a non-core localization observation from immunofluorescence-based curation. Supporting Evidence: GO_REF:0000052 Gene Ontology annotation based on curation of immunofluorescence data
GO:0016604 nuclear body	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: HPA immunofluorescence localization to nuclear bodies. As with the other nuclear annotations, this is not the site of the core cytosolic transketolase function. Reason: Non-core localization from high-throughput immunofluorescence; peripheral to transketolase's PPP function. Supporting Evidence: GO_REF:0000052 Gene Ontology annotation based on curation of immunofluorescence data
GO:0016607 nuclear speck	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: HPA immunofluorescence localization to nuclear speckles. Not the site of the core cytosolic transketolase function. Reason: Non-core localization from high-throughput immunofluorescence; peripheral to transketolase's PPP function. Supporting Evidence: GO_REF:0000052 Gene Ontology annotation based on curation of immunofluorescence data
GO:0004802 transketolase activity	EXP PMID:27259054 Mutations in TKT Are the Cause of a Syndrome Including Short...	ACCEPT	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. Reason: Strong experimental support (patient enzymology plus recombinant catalytic-activity assays); this is the core molecular function. Supporting Evidence: PMID:27259054 Enzymatic testing confirmed significantly reduced transketolase PMID:27259054 an autosomal-recessively inherited deficiency of transketolase, encoded by TKT, on chromosome 3p21
GO:0000287 magnesium ion binding	IDA PMID:9611778 Heterologous expression of human transketolase.	ACCEPT	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. Reason: Mg2+ binding is a core, mechanistically required molecular function (metal-assisted ThDP cofactor binding), directly demonstrated biochemically and structurally. Supporting Evidence: PMID:9611778 the K(m) values for thiamin diphosphate and for Mg2+ were, respectively, 4.1 +/- 0.8 and 2.5 +/- 0.4 microM PMID:9357955 aspartate 155 is an important
GO:0005509 calcium ion binding	IDA PMID:20667822 The crystal structure of human transketolase and new insight...	MARK AS OVER ANNOTATED	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). 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). Supporting Evidence: PMID:20667822 The crystal structure of human transketolase (TKT), a thiamine diphosphate (ThDP) and Ca(2+)-dependent enzyme
GO:0006098 pentose-phosphate shunt	IDA PMID:20667822 The crystal structure of human transketolase and new insight...	KEEP AS NON CORE	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. Reason: Correct but general parent term; retained as context, with GO:0009052 carrying the core, more specific process role. Supporting Evidence: PMID:20667822 catalyzes the interketol transfer between ketoses and aldoses as part of the pentose phosphate pathway
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	MARK AS OVER ANNOTATED	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. Reason: High-throughput exosome-proteome detection of an abundant cytosolic enzyme; not a functional localization for the core PPP role. Supporting Evidence: PMID:23533145 In pooled EPS-urine exosome samples, ~900 proteins were detected
GO:0031982 vesicle	HDA PMID:19190083 Characterization of exosome-like vesicles released from huma...	MARK AS OVER ANNOTATED	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. Reason: High-throughput vesicle-proteome detection of an abundant cytosolic enzyme; not a core localization. Supporting Evidence: PMID:19190083 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
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	MARK AS OVER ANNOTATED	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. Reason: High-throughput exosome-proteome detection; not a functional localization for transketolase. Supporting Evidence: PMID:19056867 the analysis identified 1132 proteins unambiguously
GO:0070062 extracellular exosome	HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote...	MARK AS OVER ANNOTATED	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. Reason: High-throughput exosome-proteome detection; not a core localization for the PPP function. Supporting Evidence: PMID:20458337 identified 539 proteins
GO:0005829 cytosol	TAS Reactome:R-HSA-163741	ACCEPT	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. Reason: Correct cytosolic localization for the core function, from a curated pathway reaction. Supporting Evidence: PMID:20667822 catalyzes the interketol transfer between ketoses and aldoses as part of the pentose phosphate pathway
GO:0005829 cytosol	TAS Reactome:R-HSA-163751	ACCEPT	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. Reason: Correct cytosolic localization for the core function, from a curated pathway reaction. Supporting Evidence: PMID:20667822 catalyzes the interketol transfer between ketoses and aldoses as part of the pentose phosphate pathway
GO:0005829 cytosol	TAS Reactome:R-HSA-71324	ACCEPT	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. Reason: Correct cytosolic localization for the core function, from a curated pathway reaction. Supporting Evidence: PMID:20667822 catalyzes the interketol transfer between ketoses and aldoses as part of the pentose phosphate pathway
GO:0005829 cytosol	TAS Reactome:R-HSA-71335	ACCEPT	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. Reason: Correct cytosolic localization for the core function, from a curated pathway reaction. Supporting Evidence: PMID:20667822 catalyzes the interketol transfer between ketoses and aldoses as part of the pentose phosphate pathway
GO:0005829 cytosol	TAS Reactome:R-HSA-9761852	ACCEPT	Summary: Reactome traceable assertion (NFE2L2-dependent TKT gene expression context) placing TKT in the cytosol. Consistent with the cytosolic localization of the enzyme. Reason: Correct cytosolic localization for the core function. Supporting Evidence: PMID:20667822 catalyzes the interketol transfer between ketoses and aldoses as part of the pentose phosphate pathway
GO:0005777 peroxisome	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	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. 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. Supporting Evidence: PMID:20667822 catalyzes the interketol transfer between ketoses and aldoses as part of the pentose phosphate pathway
GO:0009052 pentose-phosphate shunt, non-oxidative branch	NAS PMID:9357955 Aspartate 155 of human transketolase is essential for thiami...	ACCEPT	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. Reason: Correct and specific process term for transketolase's core role. Supporting Evidence: PMID:9357955 Active human transketolase is a homodimeric enzyme possessing two active sites
GO:0042803 protein homodimerization activity	IDA PMID:20667822 The crystal structure of human transketolase and new insight...	ACCEPT	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. Reason: Homodimerization is directly demonstrated and functionally required (each active site is built at the dimer interface); a genuine, well-supported molecular function. Supporting Evidence: PMID:20667822 Two monomers
GO:0042803 protein homodimerization activity	IDA PMID:9357955 Aspartate 155 of human transketolase is essential for thiami...	ACCEPT	Summary: Independent evidence that active transketolase is a homodimer and that cofactor (ThDP-Mg) binding is required for dimer formation. Reason: Directly demonstrated homodimerization coupled to cofactor binding; functionally required assembly. Supporting Evidence: PMID:9357955 Active human transketolase is a homodimeric enzyme possessing two active sites
GO:0004802 transketolase activity	IDA PMID:20667822 The crystal structure of human transketolase and new insight...	ACCEPT	Summary: Direct crystallographic and kinetic characterization of human transketolase activity, including steady-state kinetics and NMR-based intermediate analysis of the donor half-reaction. Reason: Direct experimental demonstration of the core catalytic activity. Supporting Evidence: PMID:20667822 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
GO:0004802 transketolase activity	IDA PMID:8419340 Cloning of human transketolase cDNAs and comparison of the n...	ACCEPT	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. Reason: Supports the identity and transketolase activity of the TKT gene product. Supporting Evidence: PMID:8419340 Transketolase was found to be a single copy gene which produces a single mRNA of approximately 2100 nucleotides
GO:0004802 transketolase activity	IDA PMID:9357955 Aspartate 155 of human transketolase is essential for thiami...	ACCEPT	Summary: Characterization of recombinant human transketolase, including cofactor-dependent hysteresis and the D155 mutation that abolishes activity by preventing ThDP-Mg binding and dimerization. Reason: Direct experimental characterization of transketolase activity and its cofactor requirements. Supporting Evidence: PMID:9357955 aspartate 155 is an important
GO:0004802 transketolase activity	IDA PMID:9611778 Heterologous expression of human transketolase.	ACCEPT	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. Reason: Direct enzymatic demonstration of transketolase activity with kinetic parameters. Supporting Evidence: PMID:9611778 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
GO:0046166 glyceraldehyde-3-phosphate biosynthetic process	IDA PMID:9611778 Heterologous expression of human transketolase.	KEEP AS NON CORE	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. Reason: Correct downstream consequence of transketolase catalysis (the reactions produce G3P); peripheral to the core non-oxidative PPP role. Supporting Evidence: PMID:9611778 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

Gene Description

Existing Annotations Review

Core Functions

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.

Binds thiamine diphosphate (thiamine pyrophosphate), one per subunit, as the essential catalytic cofactor that forms the covalent reaction intermediate for two-carbon transfer.

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.

References

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Notes

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