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Protein

Thiamin pyrophosphokinase 1

Gene

TPK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the phosphorylation of thiamine to thiamine pyrophosphate. Can also catalyze the phosphorylation of pyrithiamine to pyrithiamine pyrophosphate.1 Publication

Catalytic activityi

ATP + thiamine = AMP + thiamine diphosphate.

Pathwayi: thiamine diphosphate biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes thiamine diphosphate from thiamine.
Proteins known to be involved in this subpathway in this organism are:
  1. Thiamin pyrophosphokinase 1 (TPK1)
This subpathway is part of the pathway thiamine diphosphate biosynthesis, which is itself part of Cofactor biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes thiamine diphosphate from thiamine, the pathway thiamine diphosphate biosynthesis and in Cofactor biosynthesis.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS02907-MONOMER.
BRENDAi2.7.6.2. 2681.
ReactomeiR-HSA-196819. Vitamin B1 (thiamin) metabolism.
UniPathwayiUPA00060; UER00597.

Names & Taxonomyi

Protein namesi
Recommended name:
Thiamin pyrophosphokinase 1 (EC:2.7.6.2)
Short name:
hTPK1
Alternative name(s):
Placental protein 20
Short name:
PP20
Thiamine pyrophosphokinase 1
Gene namesi
Name:TPK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:17358. TPK1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

Thiamine metabolism dysfunction syndrome 5, episodic encephalopathy type (THMD5)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:614458
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06739140L → P in THMD5. 1 PublicationCorresponds to variant rs387906936dbSNPEnsembl.1
Natural variantiVAR_06739250N → H in THMD5. 1 PublicationCorresponds to variant rs387906935dbSNPEnsembl.1
Natural variantiVAR_067393219N → S in THMD5. 1 PublicationCorresponds to variant rs371271054dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi27010.
MalaCardsiTPK1.
MIMi614458. phenotype.
OpenTargetsiENSG00000196511.
Orphaneti293955. Childhood encephalopathy due to thiamine pyrophosphokinase deficiency.
PharmGKBiPA38235.

Chemistry databases

ChEMBLiCHEMBL6155.
DrugBankiDB00152. Thiamine.

Polymorphism and mutation databases

BioMutaiTPK1.
DMDMi44888537.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000726471 – 243Thiamin pyrophosphokinase 1Add BLAST243

Proteomic databases

EPDiQ9H3S4.
MaxQBiQ9H3S4.
PaxDbiQ9H3S4.
PeptideAtlasiQ9H3S4.
PRIDEiQ9H3S4.

PTM databases

iPTMnetiQ9H3S4.
PhosphoSitePlusiQ9H3S4.

Expressioni

Tissue specificityi

Detected in heart, kidney, testis, small intestine and peripheral blood leukocytes, and at very low levels in a variety of tissues.2 Publications

Gene expression databases

BgeeiENSG00000196511.
CleanExiHS_TPK1.
ExpressionAtlasiQ9H3S4. baseline and differential.
GenevisibleiQ9H3S4. HS.

Organism-specific databases

HPAiHPA021545.
HPA021849.

Interactioni

Subunit structurei

Homodimer.

Protein-protein interaction databases

IntActiQ9H3S4. 2 interactors.
MINTiMINT-3067490.
STRINGi9606.ENSP00000353165.

Structurei

Secondary structure

1243
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi19 – 23Combined sources5
Helixi32 – 38Combined sources7
Beta strandi42 – 45Combined sources4
Helixi48 – 55Combined sources8
Turni56 – 58Combined sources3
Helixi60 – 62Combined sources3
Beta strandi66 – 70Combined sources5
Beta strandi73 – 75Combined sources3
Helixi77 – 85Combined sources9
Beta strandi89 – 92Combined sources4
Helixi100 – 114Combined sources15
Beta strandi120 – 125Combined sources6
Beta strandi128 – 131Combined sources4
Helixi132 – 144Combined sources13
Helixi145 – 147Combined sources3
Beta strandi153 – 157Combined sources5
Beta strandi160 – 165Combined sources6
Beta strandi167 – 173Combined sources7
Beta strandi179 – 186Combined sources8
Beta strandi192 – 202Combined sources11
Beta strandi205 – 210Combined sources6
Turni211 – 213Combined sources3
Beta strandi216 – 219Combined sources4
Beta strandi225 – 233Combined sources9
Beta strandi235 – 241Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1OLYmodel-A/B1-243[»]
3S4YX-ray1.80A/B15-243[»]
ProteinModelPortaliQ9H3S4.
SMRiQ9H3S4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the thiamine pyrophosphokinase family.Curated

Phylogenomic databases

eggNOGiKOG3153. Eukaryota.
COG1564. LUCA.
GeneTreeiENSGT00390000016016.
HOGENOMiHOG000180834.
HOVERGENiHBG003568.
InParanoidiQ9H3S4.
KOiK00949.
OMAiTHRFLCT.
OrthoDBiEOG091G0FS8.
PhylomeDBiQ9H3S4.
TreeFamiTF313224.

Family and domain databases

CDDicd07995. TPK. 1 hit.
Gene3Di2.60.120.320. 1 hit.
3.40.50.10240. 1 hit.
InterProiIPR006282. Thi_PPkinase.
IPR016966. Thiamin_pyrophosphokinase_euk.
IPR007373. Thiamin_PyroPKinase_B1-bd.
IPR007371. TPK_catalytic.
[Graphical view]
PfamiPF04265. TPK_B1_binding. 1 hit.
PF04263. TPK_catalytic. 1 hit.
[Graphical view]
PIRSFiPIRSF031057. Thiamin_pyrophosphokinase. 1 hit.
SMARTiSM00983. TPK_B1_binding. 1 hit.
[Graphical view]
SUPFAMiSSF63862. SSF63862. 1 hit.
SSF63999. SSF63999. 1 hit.
TIGRFAMsiTIGR01378. thi_PPkinase. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9H3S4-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MEHAFTPLEP LLSTGNLKYC LVILNQPLDN YFRHLWNKAL LRACADGGAN
60 70 80 90 100
RLYDITEGER ESFLPEFING DFDSIRPEVR EYYATKGCEL ISTPDQDHTD
110 120 130 140 150
FTKCLKMLQK KIEEKDLKVD VIVTLGGLAG RFDQIMASVN TLFQATHITP
160 170 180 190 200
FPIIIIQEES LIYLLQPGKH RLHVDTGMEG DWCGLIPVGQ PCMQVTTTGL
210 220 230 240
KWNLTNDVLA FGTLVSTSNT YDGSGVVTVE TDHPLLWTMA IKS
Length:243
Mass (Da):27,265
Last modified:March 1, 2001 - v1
Checksum:iF7E96F8127CB4FA5
GO
Isoform 2 (identifier: Q9H3S4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-118: MEHAFTPLEP...QKKIEEKDLK → M
     205-243: TNDVLAFGTL...PLLWTMAIKS → RTCDYTRTTW...HICKVPLAIK

Note: No experimental confirmation available.
Show »
Length:124
Mass (Da):13,962
Checksum:i846C51E4808F336E
GO

Sequence cautioni

The sequence BAB15465 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti193M → S (PubMed:15489334).Curated1
Sequence conflicti218S → P (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06739140L → P in THMD5. 1 PublicationCorresponds to variant rs387906936dbSNPEnsembl.1
Natural variantiVAR_06739250N → H in THMD5. 1 PublicationCorresponds to variant rs387906935dbSNPEnsembl.1
Natural variantiVAR_067393219N → S in THMD5. 1 PublicationCorresponds to variant rs371271054dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0563021 – 118MEHAF…EKDLK → M in isoform 2. 1 PublicationAdd BLAST118
Alternative sequenceiVSP_056303205 – 243TNDVL…MAIKS → RTCDYTRTTWIAKDNPVPRL IRLIRLNHICKVPLAIK in isoform 2. 1 PublicationAdd BLAST39

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AC004534 Genomic DNA. No translation available.
AC004743 Genomic DNA. No translation available.
AC004833 Genomic DNA. No translation available.
AC004864 Genomic DNA. No translation available.
AC005677 Genomic DNA. No translation available.
AC074384 Genomic DNA. No translation available.
CH471146 Genomic DNA. Translation: EAW80091.1.
CH471146 Genomic DNA. Translation: EAW80092.1.
BC040555 mRNA. Translation: AAH40555.1.
BC068460 mRNA. Translation: AAH68460.1.
CCDSiCCDS5888.1. [Q9H3S4-1]
RefSeqiNP_001035947.1. NM_001042482.1.
NP_071890.2. NM_022445.3. [Q9H3S4-1]
XP_005250027.1. XM_005249970.1. [Q9H3S4-1]
XP_011514349.1. XM_011516047.2.
XP_011514350.1. XM_011516048.1.
XP_011514352.1. XM_011516050.1.
XP_016867462.1. XM_017011973.1. [Q9H3S4-1]
XP_016867471.1. XM_017011982.1.
XP_016867472.1. XM_017011983.1.
XP_016867473.1. XM_017011984.1.
XP_016867474.1. XM_017011985.1.
XP_016867475.1. XM_017011986.1.
UniGeneiHs.660232.

Genome annotation databases

EnsembliENST00000360057; ENSP00000353165; ENSG00000196511. [Q9H3S4-1]
GeneIDi27010.
KEGGihsa:27010.
UCSCiuc003weq.3. human. [Q9H3S4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AC004534 Genomic DNA. No translation available.
AC004743 Genomic DNA. No translation available.
AC004833 Genomic DNA. No translation available.
AC004864 Genomic DNA. No translation available.
AC005677 Genomic DNA. No translation available.
AC074384 Genomic DNA. No translation available.
CH471146 Genomic DNA. Translation: EAW80091.1.
CH471146 Genomic DNA. Translation: EAW80092.1.
BC040555 mRNA. Translation: AAH40555.1.
BC068460 mRNA. Translation: AAH68460.1.
CCDSiCCDS5888.1. [Q9H3S4-1]
RefSeqiNP_001035947.1. NM_001042482.1.
NP_071890.2. NM_022445.3. [Q9H3S4-1]
XP_005250027.1. XM_005249970.1. [Q9H3S4-1]
XP_011514349.1. XM_011516047.2.
XP_011514350.1. XM_011516048.1.
XP_011514352.1. XM_011516050.1.
XP_016867462.1. XM_017011973.1. [Q9H3S4-1]
XP_016867471.1. XM_017011982.1.
XP_016867472.1. XM_017011983.1.
XP_016867473.1. XM_017011984.1.
XP_016867474.1. XM_017011985.1.
XP_016867475.1. XM_017011986.1.
UniGeneiHs.660232.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1OLYmodel-A/B1-243[»]
3S4YX-ray1.80A/B15-243[»]
ProteinModelPortaliQ9H3S4.
SMRiQ9H3S4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9H3S4. 2 interactors.
MINTiMINT-3067490.
STRINGi9606.ENSP00000353165.

Chemistry databases

ChEMBLiCHEMBL6155.
DrugBankiDB00152. Thiamine.

PTM databases

iPTMnetiQ9H3S4.
PhosphoSitePlusiQ9H3S4.

Polymorphism and mutation databases

BioMutaiTPK1.
DMDMi44888537.

Proteomic databases

EPDiQ9H3S4.
MaxQBiQ9H3S4.
PaxDbiQ9H3S4.
PeptideAtlasiQ9H3S4.
PRIDEiQ9H3S4.

Protocols and materials databases

DNASUi27010.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000360057; ENSP00000353165; ENSG00000196511. [Q9H3S4-1]
GeneIDi27010.
KEGGihsa:27010.
UCSCiuc003weq.3. human. [Q9H3S4-1]

Organism-specific databases

CTDi27010.
DisGeNETi27010.
GeneCardsiTPK1.
HGNCiHGNC:17358. TPK1.
HPAiHPA021545.
HPA021849.
MalaCardsiTPK1.
MIMi606370. gene.
614458. phenotype.
neXtProtiNX_Q9H3S4.
OpenTargetsiENSG00000196511.
Orphaneti293955. Childhood encephalopathy due to thiamine pyrophosphokinase deficiency.
PharmGKBiPA38235.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3153. Eukaryota.
COG1564. LUCA.
GeneTreeiENSGT00390000016016.
HOGENOMiHOG000180834.
HOVERGENiHBG003568.
InParanoidiQ9H3S4.
KOiK00949.
OMAiTHRFLCT.
OrthoDBiEOG091G0FS8.
PhylomeDBiQ9H3S4.
TreeFamiTF313224.

Enzyme and pathway databases

UniPathwayiUPA00060; UER00597.
BioCyciZFISH:HS02907-MONOMER.
BRENDAi2.7.6.2. 2681.
ReactomeiR-HSA-196819. Vitamin B1 (thiamin) metabolism.

Miscellaneous databases

ChiTaRSiTPK1. human.
GeneWikiiTPK1.
GenomeRNAii27010.
PROiQ9H3S4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000196511.
CleanExiHS_TPK1.
ExpressionAtlasiQ9H3S4. baseline and differential.
GenevisibleiQ9H3S4. HS.

Family and domain databases

CDDicd07995. TPK. 1 hit.
Gene3Di2.60.120.320. 1 hit.
3.40.50.10240. 1 hit.
InterProiIPR006282. Thi_PPkinase.
IPR016966. Thiamin_pyrophosphokinase_euk.
IPR007373. Thiamin_PyroPKinase_B1-bd.
IPR007371. TPK_catalytic.
[Graphical view]
PfamiPF04265. TPK_B1_binding. 1 hit.
PF04263. TPK_catalytic. 1 hit.
[Graphical view]
PIRSFiPIRSF031057. Thiamin_pyrophosphokinase. 1 hit.
SMARTiSM00983. TPK_B1_binding. 1 hit.
[Graphical view]
SUPFAMiSSF63862. SSF63862. 1 hit.
SSF63999. SSF63999. 1 hit.
TIGRFAMsiTIGR01378. thi_PPkinase. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiTPK1_HUMAN
AccessioniPrimary (citable) accession number: Q9H3S4
Secondary accession number(s): A8K0T7
, D3DWG0, I6L9B8, Q6NUR5, Q9H602
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: March 1, 2001
Last modified: November 30, 2016
This is version 134 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.