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Protein

Thiamin pyrophosphokinase 1

Gene

TPK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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), Thiamine pyrophosphokinase (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

Keywordsi

Molecular functionKinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.6.2 2681
ReactomeiR-HSA-196819 Vitamin B1 (thiamin) metabolism
UniPathwayi
UPA00060;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

EuPathDBiHostDB:ENSG00000196511.13
HGNCiHGNC:17358 TPK1
MIMi606370 gene
neXtProtiNX_Q9H3S4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 dbSNP:rs387906936EnsemblClinVar.1
Natural variantiVAR_06739250N → H in THMD5. 1 PublicationCorresponds to variant dbSNP:rs387906935EnsemblClinVar.1
Natural variantiVAR_067393219N → S in THMD5. 1 PublicationCorresponds to variant dbSNP:rs371271054EnsemblClinVar.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
DrugBankiDB04768 Pyrithiamine Pyrophosphate
DB00152 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
ProteomicsDBi80748

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 Expressed in 183 organ(s), highest expression level in duodenum
CleanExiHS_TPK1
ExpressionAtlasiQ9H3S4 baseline and differential
GenevisibleiQ9H3S4 HS

Organism-specific databases

HPAiHPA021545
HPA021849

Interactioni

Subunit structurei

Homodimer.

Protein-protein interaction databases

BioGridi117952, 1 interactor
IntActiQ9H3S4, 2 interactors
MINTiQ9H3S4
STRINGi9606.ENSP00000353165

Structurei

Secondary structure

1243
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiQMEFGGM
OrthoDBiEOG091G0FS8
PhylomeDBiQ9H3S4
TreeFamiTF313224

Family and domain databases

CDDicd07995 TPK, 1 hit
Gene3Di3.40.50.10240, 1 hit
InterProiView protein in InterPro
IPR006282 Thi_PPkinase
IPR016966 Thiamin_pyrophosphokinase_euk
IPR007373 Thiamin_PyroPKinase_B1-bd
IPR036371 TPK_B1-bd_sf
IPR007371 TPK_catalytic
IPR036759 TPK_catalytic_sf
PfamiView protein in Pfam
PF04265 TPK_B1_binding, 1 hit
PF04263 TPK_catalytic, 1 hit
PIRSFiPIRSF031057 Thiamin_pyrophosphokinase, 1 hit
SMARTiView protein in SMART
SM00983 TPK_B1_binding, 1 hit
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

This entry has 2 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q6ZQX6Q6ZQX6_HUMAN
Thiamin pyrophosphokinase 1
TPK1
189Annotation score:
F5GZG6F5GZG6_HUMAN
Thiamin pyrophosphokinase 1
TPK1
194Annotation score:
F8VRJ6F8VRJ6_HUMAN
Thiamin pyrophosphokinase 1
TPK1
166Annotation score:
A0A1W2PQB3A0A1W2PQB3_HUMAN
Thiamin pyrophosphokinase 1
TPK1
135Annotation score:
F8WCM7F8WCM7_HUMAN
Thiamin pyrophosphokinase 1
TPK1
121Annotation score:
F8VPB3F8VPB3_HUMAN
Thiamin pyrophosphokinase 1
TPK1
42Annotation score:
F8VVJ1F8VVJ1_HUMAN
Thiamin pyrophosphokinase 1
TPK1
79Annotation score:

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 dbSNP:rs387906936EnsemblClinVar.1
Natural variantiVAR_06739250N → H in THMD5. 1 PublicationCorresponds to variant dbSNP:rs387906935EnsemblClinVar.1
Natural variantiVAR_067393219N → S in THMD5. 1 PublicationCorresponds to variant dbSNP:rs371271054EnsemblClinVar.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
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]
ENST00000645943; ENSP00000494003; ENSG00000285075 [Q9H3S4-1]
GeneIDi27010
KEGGihsa:27010
UCSCiuc003weq.3 human [Q9H3S4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

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
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

BioGridi117952, 1 interactor
IntActiQ9H3S4, 2 interactors
MINTiQ9H3S4
STRINGi9606.ENSP00000353165

Chemistry databases

ChEMBLiCHEMBL6155
DrugBankiDB04768 Pyrithiamine Pyrophosphate
DB00152 Thiamine

PTM databases

iPTMnetiQ9H3S4
PhosphoSitePlusiQ9H3S4

Polymorphism and mutation databases

BioMutaiTPK1
DMDMi44888537

Proteomic databases

EPDiQ9H3S4
MaxQBiQ9H3S4
PaxDbiQ9H3S4
PeptideAtlasiQ9H3S4
PRIDEiQ9H3S4
ProteomicsDBi80748

Protocols and materials databases

DNASUi27010
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000360057; ENSP00000353165; ENSG00000196511 [Q9H3S4-1]
ENST00000645943; ENSP00000494003; ENSG00000285075 [Q9H3S4-1]
GeneIDi27010
KEGGihsa:27010
UCSCiuc003weq.3 human [Q9H3S4-1]

Organism-specific databases

CTDi27010
DisGeNETi27010
EuPathDBiHostDB:ENSG00000196511.13
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
OMAiQMEFGGM
OrthoDBiEOG091G0FS8
PhylomeDBiQ9H3S4
TreeFamiTF313224

Enzyme and pathway databases

UniPathwayi
UPA00060;UER00597

BRENDAi2.7.6.2 2681
ReactomeiR-HSA-196819 Vitamin B1 (thiamin) metabolism

Miscellaneous databases

ChiTaRSiTPK1 human
GeneWikiiTPK1
GenomeRNAii27010
PROiPR:Q9H3S4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000196511 Expressed in 183 organ(s), highest expression level in duodenum
CleanExiHS_TPK1
ExpressionAtlasiQ9H3S4 baseline and differential
GenevisibleiQ9H3S4 HS

Family and domain databases

CDDicd07995 TPK, 1 hit
Gene3Di3.40.50.10240, 1 hit
InterProiView protein in InterPro
IPR006282 Thi_PPkinase
IPR016966 Thiamin_pyrophosphokinase_euk
IPR007373 Thiamin_PyroPKinase_B1-bd
IPR036371 TPK_B1-bd_sf
IPR007371 TPK_catalytic
IPR036759 TPK_catalytic_sf
PfamiView protein in Pfam
PF04265 TPK_B1_binding, 1 hit
PF04263 TPK_catalytic, 1 hit
PIRSFiPIRSF031057 Thiamin_pyrophosphokinase, 1 hit
SMARTiView protein in SMART
SM00983 TPK_B1_binding, 1 hit
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 historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: March 1, 2001
Last modified: November 7, 2018
This is version 145 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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