ID TKTL1_HUMAN Reviewed; 596 AA. AC P51854; A8K896; Q5TYJ8; Q5TYJ9; Q8TC75; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 09-JAN-2007, sequence version 2. DT 24-JUL-2024, entry version 196. DE RecName: Full=Transketolase-like protein 1; DE EC=2.2.1.1 {ECO:0000269|PubMed:15991799}; DE AltName: Full=Transketolase 2; DE Short=TK 2; DE AltName: Full=Transketolase-related protein; GN Name=TKTL1; Synonyms=TKR, TKT2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY. RC TISSUE=Fetal brain; RX PubMed=8838793; DOI=10.1006/geno.1996.0124; RA Coy J.F., Duebel S., Kioschis P., Thomas K., Micklem G., Delius H., RA Poustka A.; RT "Molecular cloning of tissue-specific transcripts of a transketolase- RT related gene: implications for the evolution of new vertebrate genes."; RL Genomics 32:309-316(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT PHE-24. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANTS PHE-24 AND RP THR-152. RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 475-537. RA Hochgeschwender U.; RL Submitted (SEP-1994) to the EMBL/GenBank/DDBJ databases. RN [7] RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=15991799; RA Coy J.F., Dressler D., Wilde J., Schubert P.; RT "Mutations in the transketolase-like gene TKTL1: clinical implications for RT neurodegenerative diseases, diabetes and cancer."; RL Clin. Lab. 51:257-273(2005). RN [8] RP FUNCTION (ISOFORM 4), VARIANT LYS-317, TISSUE SPECIFICITY (ISOFORM 4), AND RP DEVELOPMENTAL STAGE (ISOFORM 4). RX PubMed=36074851; DOI=10.1126/science.abl6422; RA Pinson A., Xing L., Namba T., Kalebic N., Peters J., Oegema C.E., RA Traikov S., Reppe K., Riesenberg S., Maricic T., Derihaci R., Wimberger P., RA Paeaebo S., Huttner W.B.; RT "Human TKTL1 implies greater neurogenesis in frontal neocortex of modern RT humans than Neanderthals."; RL Science 377:eabl6422-eabl6422(2022). CC -!- FUNCTION: Catalyzes the transfer of a two-carbon ketol group from a CC ketose donor to an aldose acceptor, via a covalent intermediate with CC the cofactor thiamine pyrophosphate. {ECO:0000250|UniProtKB:P23254}. CC -!- FUNCTION: [Isoform 4]: During fetal neocortex development, may be CC essential to maintain the full number of basal radial glia (bRG). bRG CC are neural progenitor cells that undergo asymmetric divisions, CC generating a bRG (self-renewal) and a neuron, in contrast to basal CC intermediate progenitors (bIPs), which typically divide once to give CC rise to 2 neurons. bRG generate more cortical neurons over time than CC bIPs. {ECO:0000269|PubMed:36074851}. CC -!- CATALYTIC ACTIVITY: CC Reaction=D-glyceraldehyde 3-phosphate + D-sedoheptulose 7-phosphate = CC aldehydo-D-ribose 5-phosphate + D-xylulose 5-phosphate; CC Xref=Rhea:RHEA:10508, ChEBI:CHEBI:57483, ChEBI:CHEBI:57737, CC ChEBI:CHEBI:58273, ChEBI:CHEBI:59776; EC=2.2.1.1; CC Evidence={ECO:0000269|PubMed:15991799}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:10510; CC Evidence={ECO:0000269|PubMed:15991799}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P23254}; CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000250|UniProtKB:P23254}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000250|UniProtKB:P23254}; CC Name=Co(2+); Xref=ChEBI:CHEBI:48828; CC Evidence={ECO:0000250|UniProtKB:P23254}; CC Note=Binds 1 Mg(2+) ion per subunit. Can also utilize other divalent CC metal cations, such as Ca(2+), Mn(2+) and Co(2+). CC {ECO:0000250|UniProtKB:P23254}; CC -!- COFACTOR: CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937; CC Evidence={ECO:0000250|UniProtKB:P23254}; CC Note=Binds 1 thiamine pyrophosphate per subunit. CC {ECO:0000250|UniProtKB:P23254}; CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P23254}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:15991799}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=3; Synonyms=Long {ECO:0000303|PubMed:36074851}; CC IsoId=P51854-3; Sequence=Displayed; CC Name=2; CC IsoId=P51854-1; Sequence=VSP_022290, VSP_022291; CC Name=4; Synonyms=Short {ECO:0000303|PubMed:36074851}; CC IsoId=P51854-4; Sequence=VSP_022290; CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:8838793). Expressed in CC endothelial cells and in peripheral neurons (at protein level) CC (PubMed:15991799). {ECO:0000269|PubMed:15991799, CC ECO:0000269|PubMed:8838793}. CC -!- TISSUE SPECIFICITY: [Isoform 3]: Not expressed in fetal neocortex. CC {ECO:0000269|PubMed:36074851}. CC -!- TISSUE SPECIFICITY: [Isoform 4]: Expressed in fetal neocortex. CC {ECO:0000269|PubMed:36074851}. CC -!- DEVELOPMENTAL STAGE: [Isoform 4]: Expressed in fetal neocortex, with CC highest expression in the developing frontal lobe. Expression increases CC with development from 9 to at least 17 postconception weeks (PCW). At CC 11 PCW, expression in frontal lobe is detectable in the ventricular CC zone and subventricular zone. At PCW 17, highly expressed in the CC frontal lobe of fetal neocortex, but not in the occipital lobe. CC {ECO:0000269|PubMed:36074851}. CC -!- POLYMORPHISM: Variant Lys-317 is typically present in extinct archaic CC humans, Neanderthals and Denisovans, as well as in other primates. It CC is rare in modern human population with a frequency of 0.03%. No CC homozygote is reported in the Genome Aggregation Database (gnomAD CC v2.1.1). The modern human variant Arg-317 is thought to lead to a CC greater neocortical neurogenesis compared to archaic human Lys-317, in CC particular in the frontal lobe. It is currently unknown if the presence CC of variant Lys-317 in modern humans is associated with a disease or has CC any effect on cognitive skills. {ECO:0000269|PubMed:36074851}. CC -!- SIMILARITY: Belongs to the transketolase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X91817; CAA62925.1; -; mRNA. DR EMBL; X91818; CAA62925.1; JOINED; mRNA. DR EMBL; AK292261; BAF84950.1; -; mRNA. DR EMBL; BX664723; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; Z49258; CAH69899.1; -; Genomic_DNA. DR EMBL; Z49258; CAH69900.1; -; Genomic_DNA. DR EMBL; CH471172; EAW72752.1; -; Genomic_DNA. DR EMBL; BC025382; AAH25382.2; -; mRNA. DR EMBL; U14622; AAA21557.1; -; Genomic_DNA. DR CCDS; CCDS35448.1; -. [P51854-3] DR CCDS; CCDS55541.1; -. [P51854-4] DR RefSeq; NP_001139406.1; NM_001145934.1. [P51854-4] DR RefSeq; NP_036385.3; NM_012253.3. [P51854-3] DR AlphaFoldDB; P51854; -. DR SMR; P51854; -. DR BioGRID; 113890; 14. DR IntAct; P51854; 6. DR STRING; 9606.ENSP00000358931; -. DR DrugCentral; P51854; -. DR iPTMnet; P51854; -. DR PhosphoSitePlus; P51854; -. DR BioMuta; TKTL1; -. DR DMDM; 122066426; -. DR jPOST; P51854; -. DR MassIVE; P51854; -. DR PaxDb; 9606-ENSP00000358931; -. DR PeptideAtlas; P51854; -. DR ProteomicsDB; 56434; -. [P51854-3] DR ProteomicsDB; 56435; -. [P51854-1] DR ProteomicsDB; 65205; -. DR Antibodypedia; 17549; 79 antibodies from 22 providers. DR DNASU; 8277; -. DR Ensembl; ENST00000369912.2; ENSP00000358928.2; ENSG00000007350.18. [P51854-4] DR Ensembl; ENST00000369915.8; ENSP00000358931.3; ENSG00000007350.18. [P51854-3] DR GeneID; 8277; -. DR KEGG; hsa:8277; -. DR MANE-Select; ENST00000369915.8; ENSP00000358931.3; NM_012253.4; NP_036385.3. DR UCSC; uc004fkg.4; human. [P51854-3] DR AGR; HGNC:11835; -. DR CTD; 8277; -. DR DisGeNET; 8277; -. DR GeneCards; TKTL1; -. DR HGNC; HGNC:11835; TKTL1. DR HPA; ENSG00000007350; Tissue enriched (testis). DR MIM; 300044; gene. DR neXtProt; NX_P51854; -. DR OpenTargets; ENSG00000007350; -. DR PharmGKB; PA36538; -. DR VEuPathDB; HostDB:ENSG00000007350; -. DR eggNOG; KOG0523; Eukaryota. DR GeneTree; ENSGT00940000162426; -. DR HOGENOM; CLU_009227_3_0_1; -. DR InParanoid; P51854; -. DR OMA; EWTTGNL; -. DR OrthoDB; 178912at2759; -. DR PhylomeDB; P51854; -. DR TreeFam; TF313097; -. DR BRENDA; 2.2.1.1; 2681. DR PathwayCommons; P51854; -. DR SABIO-RK; P51854; -. DR SignaLink; P51854; -. DR BioGRID-ORCS; 8277; 9 hits in 771 CRISPR screens. DR ChiTaRS; TKTL1; human. DR GeneWiki; TKTL1; -. DR GenomeRNAi; 8277; -. DR Pharos; P51854; Tbio. DR PRO; PR:P51854; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; P51854; Protein. DR Bgee; ENSG00000007350; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 110 other cell types or tissues. DR ExpressionAtlas; P51854; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0030976; F:thiamine pyrophosphate binding; IBA:GO_Central. DR GO; GO:0004802; F:transketolase activity; IBA:GO_Central. DR GO; GO:0006007; P:glucose catabolic process; TAS:ProtInc. DR GO; GO:0006772; P:thiamine metabolic process; TAS:ProtInc. DR CDD; cd07033; TPP_PYR_DXS_TK_like; 1. DR Gene3D; 3.40.50.920; -; 1. DR Gene3D; 3.40.50.970; -; 2. DR InterPro; IPR029061; THDP-binding. DR InterPro; IPR009014; Transketo_C/PFOR_II. DR InterPro; IPR051424; Transketolase-like. DR InterPro; IPR005475; Transketolase-like_Pyr-bd. DR InterPro; IPR020826; Transketolase_BS. DR InterPro; IPR033248; Transketolase_C. DR InterPro; IPR005474; Transketolase_N. DR PANTHER; PTHR43195; TRANSKETOLASE; 1. DR PANTHER; PTHR43195:SF2; TRANSKETOLASE-LIKE PROTEIN 1; 1. DR Pfam; PF02779; Transket_pyr; 1. DR Pfam; PF02780; Transketolase_C; 1. DR Pfam; PF00456; Transketolase_N; 1. DR SMART; SM00861; Transket_pyr; 1. DR SUPFAM; SSF52518; Thiamin diphosphate-binding fold (THDP-binding); 2. DR SUPFAM; SSF52922; TK C-terminal domain-like; 1. DR PROSITE; PS00802; TRANSKETOLASE_2; 1. PE 1: Evidence at protein level; KW Alternative splicing; Calcium; Cytoplasm; Developmental protein; Magnesium; KW Metal-binding; Reference proteome; Thiamine pyrophosphate; Transferase. FT CHAIN 1..596 FT /note="Transketolase-like protein 1" FT /id="PRO_0000191899" FT REGION 256..277 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 340 FT /note="Proton donor" FT /evidence="ECO:0000250|UniProtKB:P27302" FT BINDING 46 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P27302" FT BINDING 49 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /evidence="ECO:0000250|UniProtKB:P23254" FT BINDING 94..96 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /evidence="ECO:0000250|UniProtKB:P23254" FT BINDING 126 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P27302" FT BINDING 127 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /evidence="ECO:0000250|UniProtKB:P23254" FT BINDING 156 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P27302" FT BINDING 156 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /evidence="ECO:0000250|UniProtKB:P23254" FT BINDING 158 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P27302" FT BINDING 218 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /evidence="ECO:0000250" FT BINDING 232 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P27302" FT BINDING 232 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /evidence="ECO:0000250|UniProtKB:P23254" FT BINDING 292 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P27302" FT BINDING 319 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P27302" FT BINDING 340 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /evidence="ECO:0000250|UniProtKB:P23254" FT BINDING 366 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /evidence="ECO:0000250|UniProtKB:P23254" FT BINDING 390 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P27302" FT BINDING 398 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P27302" FT BINDING 402 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /evidence="ECO:0000250|UniProtKB:P27302" FT BINDING 448 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P27302" FT SITE 46 FT /note="Important for catalytic activity" FT /evidence="ECO:0000250|UniProtKB:P23254" FT SITE 232 FT /note="Important for catalytic activity" FT /evidence="ECO:0000250|UniProtKB:P23254" FT VAR_SEQ 1..56 FT /note="Missing (in isoform 2 and isoform 4)" FT /evidence="ECO:0000303|PubMed:8838793" FT /id="VSP_022290" FT VAR_SEQ 467 FT /note="K -> KGVSMLQDSWSSVISYQK (in isoform 2)" FT /evidence="ECO:0000303|PubMed:8838793" FT /id="VSP_022291" FT VARIANT 24 FT /note="L -> F (in dbSNP:rs17855509)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:15772651" FT /id="VAR_029867" FT VARIANT 152 FT /note="I -> T (in dbSNP:rs17852259)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_029868" FT VARIANT 317 FT /note="R -> K (in dbSNP:rs111811311)" FT /evidence="ECO:0000269|PubMed:36074851" FT /id="VAR_087456" FT CONFLICT 519 FT /note="I -> N (in Ref. 6; AAA21557)" FT /evidence="ECO:0000305" FT CONFLICT 532 FT /note="T -> S (in Ref. 6; AAA21557)" FT /evidence="ECO:0000305" SQ SEQUENCE 596 AA; 65333 MW; F492A902441E2A14 CRC64; MADAEARAEF PEEARPDRGT LQVLQDMASR LRIHSIRATC STSSGHPTSC SSSSEIMSVL FFYIMRYKQS DPENPDNDRF VLAKRLSFVD VATGWLGQGL GVACGMAYTG KYFDRASYRV FCLMSDGESS EGSVWEAMAF ASYYSLDNLV AIFDVNRLGH SGALPAEHCI NIYQRRCEAF GWNTYVVDGR DVEALCQVFW QASQVKHKPT AVVAKTFKGR GTPSIEDAES WHAKPMPRER ADAIIKLIES QIQTSRNLDP QPPIEDSPEV NITDVRMTSP PDYRVGDKIA TRKACGLALA KLGYANNRVV VLDGDTRYST FSEIFNKEYP ERFIECFMAE QNMVSVALGC ASRGRTIAFA STFAAFLTRA FDHIRIGGLA ESNINIIGSH CGVSVGDDGA SQMALEDIAM FRTIPKCTIF YPTDAVSTEH AVALAANAKG MCFIRTTRPE TMVIYTPQER FEIGQAKVLR HCVSDKVTVI GAGITVYEAL AAADELSKQD IFIRVIDLFT IKPLDVATIV SSAKATEGRI ITVEDHYPQG GIGEAVCAAV SMDPDIQVHS LAVSGVPQSG KSEELLDMYG ISARHIIVAV KCMLLN //