Q9H3S4 (TPK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thiamin pyrophosphokinase 1
Short name=hTPK1
EC=2.7.6.2

Alternative name(s):
Placental protein 20
Short name=PP20
Thiamine pyrophosphokinase 1

Gene names

Name:

TPK1

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	243 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the phosphorylation of thiamine to thiamine pyrophosphate. Can also catalyze the phosphorylation of pyrithiamine to pyrithiamine pyrophosphate. Ref.1
Catalytic activity	ATP + thiamine = AMP + thiamine diphosphate.
Pathway	Cofactor biosynthesis; thiamine diphosphate biosynthesis; thiamine diphosphate from thiamine: step 1/1.
Subunit structure	Homodimer.
Tissue specificity	Detected in heart, kidney, testis, small intestine and peripheral blood leukocytes, and at very low levels in a variety of tissues. Ref.1 Ref.2
Involvement in disease	Thiamine metabolism dysfunction syndrome 5, episodic encephalopathy type (THMD5) [MIM:614458]: An autosomal recessive metabolic disorder due to an inborn error of thiamine metabolism. The phenotype is highly variable, but in general, affected individuals have onset in early childhood of acute encephalopathic episodes associated with increased serum and CSF lactate. These episodes result in progressive neurologic dysfunction manifest as gait disturbances, ataxia, dystonia, and spasticity, which in some cases may result in loss of ability to walk. Cognitive function is usually preserved, although mildly delayed development has been reported. These episodes are usually associated with infection and metabolic decompensation. Some patients may have recovery of some neurologic deficits. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7
Sequence similarities	Belongs to the thiamine pyrophosphokinase family.
Sequence caution	The sequence BAB15465.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Disease	Disease mutation
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	thiamine diphosphate biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway thiamine metabolic process Inferred from electronic annotation. Source: Compara thiamine-containing compound metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW kinase activity Inferred from electronic annotation. Source: UniProtKB-KW thiamine diphosphokinase activity Traceable author statement. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 243

243

Thiamin pyrophosphokinase 1

PRO_0000072647

Natural variations

Natural variant

40

1

L → P in THMD5. Ref.7

VAR_067391

Natural variant

50

1

N → H in THMD5. Ref.7

VAR_067392

Natural variant

219

1

N → S in THMD5. Ref.7

VAR_067393

Experimental info

Sequence conflict

193

1

M → S Ref.6

Sequence conflict

218

1

S → P Ref.4

Secondary structure

1

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243

Helix Strand Turn

Details...

Beta strand

19 – 23

5

Helix

32 – 38

7

Beta strand

42 – 45

4

Helix

48 – 55

8

Turn

56 – 58

3

Helix

60 – 62

3

Beta strand

66 – 70

5

Beta strand

73 – 75

3

Helix

77 – 85

9

Beta strand

89 – 92

4

Helix

100 – 114

15

Beta strand

120 – 125

6

Beta strand

128 – 131

4

Helix

132 – 144

13

Helix

145 – 147

3

Beta strand

153 – 157

5

Beta strand

160 – 165

6

Beta strand

167 – 173

7

Beta strand

179 – 186

8

Beta strand

192 – 202

11

Beta strand

205 – 210

6

Turn

211 – 213

3

Beta strand

216 – 219

4

Beta strand

225 – 233

9

Beta strand

235 – 241

7

Sequences

	Sequence		Length	Mass (Da)
	Q9H3S4 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: F7E96F8127CB4FA5	FASTA	243	27,265
	10 20 30 40 50 60 MEHAFTPLEP LLSTGNLKYC LVILNQPLDN YFRHLWNKAL LRACADGGAN RLYDITEGER 70 80 90 100 110 120 ESFLPEFING DFDSIRPEVR EYYATKGCEL ISTPDQDHTD FTKCLKMLQK KIEEKDLKVD 130 140 150 160 170 180 VIVTLGGLAG RFDQIMASVN TLFQATHITP FPIIIIQEES LIYLLQPGKH RLHVDTGMEG 190 200 210 220 230 240 DWCGLIPVGQ PCMQVTTTGL KWNLTNDVLA FGTLVSTSNT YDGSGVVTVE TDHPLLWTMA IKS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of a human thiamine pyrophosphokinase cDNA." Nosaka K., Onozuka M., Kakazu N., Hibi S., Nishimura H., Nishino H., Abe T. Biochim. Biophys. Acta 1517:293-297(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY. Tissue: Liver.
[2]	"Molecular cloning of human thiamin pyrophosphokinase." Zhao R., Gao F., Goldman I.D. Biochim. Biophys. Acta 1517:320-322(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Liver.
[3]	"Cloning, sequencing, structural and molecular biological characterization of placental protein 20 (PP20)/human thiamin pyrophosphokinase (hTPK)." Bellyei S., Szigeti A., Boronkai A., Szabo Z., Bene J., Janaky T., Barna L., Sipos K., Minik O., Kravjak A., Ohmacht R., Melegh B., Zavodszky P., Than G.N., Sumegi B., Bohn H., Than N.G. Placenta 26:34-46(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"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]. Tissue: Amygdala and Small intestine.
[5]	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].
[6]	"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]. Tissue: Hypothalamus.
[7]	"Thiamine pyrophosphokinase deficiency in encephalopathic children with defects in the pyruvate oxidation pathway." Mayr J.A., Freisinger P., Schlachter K., Rolinski B., Zimmermann F.A., Scheffner T., Haack T.B., Koch J., Ahting U., Prokisch H., Sperl W. Am. J. Hum. Genet. 89:806-812(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THMD5 PRO-40; HIS-50 AND SER-219.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB028138 mRNA. Translation: BAB20326.1.
AF297710 mRNA. Translation: AAK01351.1.
AY206415 mRNA. Translation: AAO38775.1.
AK026374 mRNA. Translation: BAB15465.1. Different initiation.
AK289652 mRNA. Translation: BAF82341.1.
CH471146 Genomic DNA. Translation: EAW80091.1.
CH471146 Genomic DNA. Translation: EAW80092.1.
BC068460 mRNA. Translation: AAH68460.1.

IPI

IPI00072523.

RefSeq

NP_071890.2. NM_022445.3.

UniGene

Hs.660232.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1OLY	model	-	A/B	1-243	[»]
3S4Y	X-ray	1.80	A/B	15-243	[»]

ProteinModelPortal

Q9H3S4.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000353165.

PTM databases

PhosphoSite

Q9H3S4.

Polymorphism databases

DMDM

44888537.

Proteomic databases

PaxDb

Q9H3S4.

PRIDE

Q9H3S4.

Protocols and materials databases

DNASU

27010.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000360057; ENSP00000353165; ENSG00000196511.

GeneID

27010.

KEGG

hsa:27010.

UCSC

uc003weq.3. human.

Organism-specific databases

CTD

27010.

GeneCards

GC07M144149.

HGNC

HGNC:17358. TPK1.

HPA

HPA021545.
HPA021849.

MIM

606370. gene.
614458. phenotype.

neXtProt

NX_Q9H3S4.

Orphanet

293955. Childhood encephalopathy due to thiamine pyrophosphokinase deficiency.

PharmGKB

PA38235.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1564.

HOGENOM

HOG000180834.

HOVERGEN

HBG003568.

InParanoid

Q9H3S4.

KO

K00949.

OMA

KYCLVIL.

OrthoDB

EOG4DJJX5.

PhylomeDB

Q9H3S4.

Enzyme and pathway databases

BRENDA

2.7.6.2. 2681.

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00060; UER00597.

Gene expression databases

ArrayExpress

Q9H3S4.

Bgee

Q9H3S4.

CleanEx

HS_TPK1.

Genevestigator

Q9H3S4.

GermOnline

ENSG00000196511. Homo sapiens.

Family and domain databases

Gene3D

2.60.120.320. 1 hit.
3.40.50.10240. 1 hit.

InterPro

IPR006282. Thi_PPkinase.
IPR016966. Thiamin_pyrophosphokinase_euk.
IPR007373. Thiamin_PyroPKinase_B1-bd.
IPR007371. TPK_catalytic.
[Graphical view]

Pfam

PF04265. TPK_B1_binding. 1 hit.
PF04263. TPK_catalytic. 1 hit.
[Graphical view]

PIRSF

PIRSF031057. Thiamin_pyrophosphokinase. 1 hit.

SMART

SM00983. TPK_B1_binding. 1 hit.
[Graphical view]

SUPFAM

SSF63862. TPK_B1_bd. 1 hit.
SSF63999. TPK_catalytic. 1 hit.

TIGRFAMs

TIGR01378. thi_PPkinase. 1 hit.

ProtoNet

Search...

Other

ChEMBL

CHEMBL6155.

ChiTaRS

TPK1. human.

DrugBank

DB00152. Thiamine.

GenomeRNAi

27010.

NextBio

49516.

SOURCE

Search...

Entry information

Entry name

TPK1_HUMAN

Accession

Primary (citable) accession number: Q9H3S4
Secondary accession number(s): A8K0T7 , D3DWG0, Q6NUR5, Q9H602

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 2004
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 101 of the entry and version 1 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.