P51854 (TKTL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transketolase-like protein 1
EC=2.2.1.1

Alternative name(s):
Transketolase 2
Short name=TK 2
Transketolase-related protein

Gene names

Name:	TKTL1
Synonyms:	TKR, TKT2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	596 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate By similarity.
Catalytic activity	Sedoheptulose 7-phosphate + D-glyceraldehyde 3-phosphate = D-ribose 5-phosphate + D-xylulose 5-phosphate. Ref.7
Cofactor	Binds 1 magnesium ion per subunit. Can also utilize other divalent metal cations, such as Ca2+, Mn2+ and Co2+ By similarity. Binds 1 thiamine pyrophosphate per subunit By similarity.
Subunit structure	Homodimer By similarity.
Subcellular location	Cytoplasm. Nucleus. Note: Predominantly cytoplasmic and to a lesser extent also nuclear. Ref.7 Ref.8 Ref.9
Tissue specificity	Expressed in fetal and adult heart, brain, lung, liver, and kidney, and in adult placenta, skeletal muscle and pancreas. Up-regulated in various epithelial tumors. Ref.1 Ref.7 Ref.8 Ref.9
Miscellaneous	Strong TKTL1 protein expression has been correlated with a certain type of glucose metabolism (aerobic glycolysis; Warburg effect) and to cells which are affected by chronic complications of diabetic patients.
Sequence similarities	Belongs to the transketolase family.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Calcium Magnesium Metal-binding Thiamine pyrophosphate
Molecular function	Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	glucose catabolic process Traceable author statement Ref.1. Source: ProtInc thiamine metabolic process Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW transketolase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 3 (identifier: P51854-3)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P51854-1)

Also known as: Brain specific;

The sequence of this isoform differs from the canonical sequence as follows:
     1-56: Missing.
     467-467: K → KGVSMLQDSWSSVISYQK

Isoform 1 (identifier: P51854-2)

Also known as: Heart specific;

The sequence of this isoform is not available.

Note: Lacks the N-terminal.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 596	596	Transketolase-like protein 1		PRO_0000191899
Regions
	Nucleotide binding	94 – 96	3	Thiamine pyrophosphate By similarity
Sites
	Active site	340	1	Proton donor By similarity
	Metal binding	126	1	Magnesium By similarity
	Metal binding	156	1	Magnesium By similarity
	Metal binding	158	1	Magnesium; via carbonyl oxygen By similarity
	Binding site	46	1	Substrate By similarity
	Binding site	49	1	Thiamine pyrophosphate By similarity
	Binding site	127	1	Thiamine pyrophosphate; via amide nitrogen By similarity
	Binding site	156	1	Thiamine pyrophosphate By similarity
	Binding site	218	1	Thiamine pyrophosphate By similarity
	Binding site	232	1	Substrate By similarity
	Binding site	232	1	Thiamine pyrophosphate By similarity
	Binding site	292	1	Substrate By similarity
	Binding site	319	1	Substrate By similarity
	Binding site	366	1	Thiamine pyrophosphate By similarity
	Binding site	390	1	Substrate By similarity
	Binding site	398	1	Substrate By similarity
	Binding site	402	1	Thiamine pyrophosphate By similarity
	Binding site	448	1	Substrate By similarity
	Site	46	1	Important for catalytic activity By similarity
	Site	232	1	Important for catalytic activity By similarity
Natural variations
	Alternative sequence	1 – 56	56	Missing in isoform 2.		VSP_022290
	Alternative sequence	467	1	K → KGVSMLQDSWSSVISYQK in isoform 2.		VSP_022291
	Natural variant	24	1	L → F. Ref.3 Ref.5 Corresponds to variant rs17855509 [ dbSNP | Ensembl ].		VAR_029867
	Natural variant	152	1	I → T. Ref.5 Corresponds to variant rs17852259 [ dbSNP | Ensembl ].		VAR_029868
Experimental info
	Sequence conflict	519	1	I → N in AAA21557. Ref.6
	Sequence conflict	532	1	T → S in AAA21557. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 3 [UniParc]. Last modified January 9, 2007. Version 2. Checksum: F492A902441E2A14	FASTA	596	65,333
	10 20 30 40 50 60 MADAEARAEF PEEARPDRGT LQVLQDMASR LRIHSIRATC STSSGHPTSC SSSSEIMSVL 70 80 90 100 110 120 FFYIMRYKQS DPENPDNDRF VLAKRLSFVD VATGWLGQGL GVACGMAYTG KYFDRASYRV 130 140 150 160 170 180 FCLMSDGESS EGSVWEAMAF ASYYSLDNLV AIFDVNRLGH SGALPAEHCI NIYQRRCEAF 190 200 210 220 230 240 GWNTYVVDGR DVEALCQVFW QASQVKHKPT AVVAKTFKGR GTPSIEDAES WHAKPMPRER 250 260 270 280 290 300 ADAIIKLIES QIQTSRNLDP QPPIEDSPEV NITDVRMTSP PDYRVGDKIA TRKACGLALA 310 320 330 340 350 360 KLGYANNRVV VLDGDTRYST FSEIFNKEYP ERFIECFMAE QNMVSVALGC ASRGRTIAFA 370 380 390 400 410 420 STFAAFLTRA FDHIRIGGLA ESNINIIGSH CGVSVGDDGA SQMALEDIAM FRTIPKCTIF 430 440 450 460 470 480 YPTDAVSTEH AVALAANAKG MCFIRTTRPE TMVIYTPQER FEIGQAKVLR HCVSDKVTVI 490 500 510 520 530 540 GAGITVYEAL AAADELSKQD IFIRVIDLFT IKPLDVATIV SSAKATEGRI ITVEDHYPQG 550 560 570 580 590 GIGEAVCAAV SMDPDIQVHS LAVSGVPQSG KSEELLDMYG ISARHIIVAV KCMLLN
	Isoform 2 (Brain specific) [UniParc]. Checksum: 3F773DB8469447F7	FASTA	557	61,200
	10 20 30 40 50 60 MSVLFFYIMR YKQSDPENPD NDRFVLAKRL SFVDVATGWL GQGLGVACGM AYTGKYFDRA 70 80 90 100 110 120 SYRVFCLMSD GESSEGSVWE AMAFASYYSL DNLVAIFDVN RLGHSGALPA EHCINIYQRR 130 140 150 160 170 180 CEAFGWNTYV VDGRDVEALC QVFWQASQVK HKPTAVVAKT FKGRGTPSIE DAESWHAKPM 190 200 210 220 230 240 PRERADAIIK LIESQIQTSR NLDPQPPIED SPEVNITDVR MTSPPDYRVG DKIATRKACG 250 260 270 280 290 300 LALAKLGYAN NRVVVLDGDT RYSTFSEIFN KEYPERFIEC FMAEQNMVSV ALGCASRGRT 310 320 330 340 350 360 IAFASTFAAF LTRAFDHIRI GGLAESNINI IGSHCGVSVG DDGASQMALE DIAMFRTIPK 370 380 390 400 410 420 CTIFYPTDAV STEHAVALAA NAKGMCFIRT TRPETMVIYT PQERFEIGQA KGVSMLQDSW 430 440 450 460 470 480 SSVISYQKVL RHCVSDKVTV IGAGITVYEA LAAADELSKQ DIFIRVIDLF TIKPLDVATI 490 500 510 520 530 540 VSSAKATEGR IITVEDHYPQ GGIGEAVCAA VSMDPDIQVH SLAVSGVPQS GKSEELLDMY 550 GISARHIIVA VKCMLLN
	Isoform 1 (Heart specific) (Sequence not available).		–	–

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of tissue-specific transcripts of a transketolase-related gene: implications for the evolution of new vertebrate genes." Coy J.F., Duebel S., Kioschis P., Thomas K., Micklem G., Delius H., Poustka A. Genomics 32:309-316(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY. Tissue: Fetal brain.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Testis.
[3]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT PHE-24.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANTS PHE-24 AND THR-152. Tissue: Testis.
[6]	Hochgeschwender U. Submitted (SEP-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 475-537 (ISOFORMS 1/2).
[7]	"Mutations in the transketolase-like gene TKTL1: clinical implications for neurodegenerative diseases, diabetes and cancer." Coy J.F., Dressler D., Wilde J., Schubert P. Clin. Lab. 51:257-273(2005) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[8]	"Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted." Langbein S., Zerilli M., Zur Hausen A., Staiger W., Rensch-Boschert K., Lukan N., Popa J., Ternullo M.P., Steidler A., Weiss C., Grobholz R., Willeke F., Alken P., Stassi G., Schubert P., Coy J.F. Br. J. Cancer 94:578-585(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]	"Expression of the mutated transketolase TKTL1, a molecular marker in gastric cancer." Staiger W.I., Coy J.F., Grobholz R., Hofheinz R.-D., Lukan N., Post S., Schwarzbach M.H., Willeke F. Oncol. Rep. 16:657-661(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X91817, X91818 mRNA. Translation: CAA62925.1. AK292261 mRNA. Translation: BAF84950.1. Z49258 Genomic DNA. Translation: CAH69899.1. CH471172 Genomic DNA. Translation: EAW72752.1. BC025382 mRNA. Translation: AAH25382.2. U14622 Genomic DNA. Translation: AAA21557.1.
IPI	IPI00644689. IPI00747585.
RefSeq	NP_001139406.1. NM_001145934.1. NP_036385.3. NM_012253.3.
UniGene	Hs.102866.
3D structure databases
ProteinModelPortal	P51854.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000358931.
PTM databases
PhosphoSite	P51854.
Polymorphism databases
DMDM	122066426.
Proteomic databases
PaxDb	P51854.
PRIDE	P51854.
Protocols and materials databases
DNASU	8277.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000369915; ENSP00000358931; ENSG00000007350. ENST00000596987; ENSP00000472763; ENSG00000268013.
GeneID	8277.
KEGG	hsa:8277.
UCSC	uc004fkg.3. human.
Organism-specific databases
CTD	8277.
GeneCards	GC0XP153524.
H-InvDB	HIX0017149.
HGNC	HGNC:11835. TKTL1.
HPA	CAB032191. HPA000505.
MIM	300044. gene.
neXtProt	NX_P51854.
PharmGKB	PA36538.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0021.
HOGENOM	HOG000243868.
HOVERGEN	HBG004036.
InParanoid	P51854.
KO	K00615.
OMA	QPPIEDS.
OrthoDB	EOG4R23TG.
Enzyme and pathway databases
SABIO-RK	P51854.
Gene expression databases
ArrayExpress	P51854.
Bgee	P51854.
CleanEx	HS_TKTL1.
Genevestigator	P51854.
GermOnline	ENSG00000007350. Homo sapiens.
Family and domain databases
Gene3D	3.40.50.920. 1 hit.
InterPro	IPR009014. Transketo_C/Pyr-ferredox_oxred. IPR015941. Transketolase-like_C. IPR005475. Transketolase-like_Pyr-bd. IPR020826. Transketolase_BS. IPR005476. Transketolase_C. IPR005474. Transketolase_N. [Graphical view]
Pfam	PF02779. Transket_pyr. 1 hit. PF02780. Transketolase_C. 1 hit. PF00456. Transketolase_N. 2 hits. [Graphical view]
SMART	SM00861. Transket_pyr. 1 hit. [Graphical view]
SUPFAM	SSF52922. Transketo_C_like. 1 hit.
PROSITE	PS00801. TRANSKETOLASE_1. False negative. PS00802. TRANSKETOLASE_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	8277.
NextBio	31045.
SOURCE	Search...

Entry information

Entry name

TKTL1_HUMAN

Accession

Primary (citable) accession number: P51854
Secondary accession number(s): A8K896, Q5TYJ9, Q8TC75

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	January 9, 2007
Last modified:	May 1, 2013
This is version 121 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.