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Information on EC 2.7.6.2 - thiamine diphosphokinase and Organism(s) Homo sapiens
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2.7.6.2 thiamine diphosphokinaseSpecify your search results
Word Map
- 2.7.6.2
- pyrophosphate
- dihydropteroate
-
pyrophosphorylated
- tdp
-
ribosephosphate
-
hydroxymethyldihydropterin
- pyrithiamine
- 6-hydroxymethyl-7,8-dihydropterin
- dihydroneopterin
-
thiamine-responsive
- oxythiamine
-
megaloblastic
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
thiamine pyrophosphokinase, pyrophosphokinase, htpk1, thiamin pyrophosphotransferase, thiamine diphosphokinase, thiamin:atp pyrophosphotransferase, thiaminokinase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ATP:thiamin pyrophosphotransferase
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-
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hTPK1
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pyrophosphokinase, thiamin
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-
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thiamin kinase
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thiamin pyrophosphokinase
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thiamin pyrophosphotransferase
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thiamin:ATP pyrophosphotransferase
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thiamine kinase
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thiamine pyrophosphokinase
thiaminokinase
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TPK
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Tpk1
TPTase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diphosphate transfer
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-
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SYSTEMATIC NAME
IUBMB Comments
ATP:thiamine diphosphotransferase
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CAS REGISTRY NUMBER
COMMENTARY
9026-24-8
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
CTP + thiamine
CMP + thiamine diphosphate
31.4% of the activity with ATP
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-
?
GTP + thiamine
GMP + thiamine diphosphate
18.3% of the activity with ATP
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-
?
UTP + thiamine
UMP + thiamine diphosphate
207% of the activity with ATP
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-
?
additional information
?
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three common intronic variants in the maternal and fetal thiamine pyrophosphokinase gene (TPK1) are associated with birth weight, overview
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?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
three common intronic variants in the maternal and fetal thiamine pyrophosphokinase gene (TPK1) are associated with birth weight, overview
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-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ALT-711
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low-affinity inhibitor, mixed-mode inhibition with a major role for competitive inhibition
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
TPK1 mutations cause thiamine pyrophosphokinase deficiency, a treatable neurological disorder. Diagnosis of TPK deficiency in a clinical setting, overview. TPK1 mutations result in episodic encephalopathy type thiamine metabolism dysfunction is the most recently described disorder of this group
physiological function
physiological function
thiamine diphosphate is a cofactor for enzymes important in a range of fundamental processes such as cellular respiration (pyruvate dehydrogenase and 2-ketoglutarate dehydrogenase) and in providing substrates for synthesis of nucleic acids, nucleotides, fatty acids and steroids (transketolase in the pentose phosphate pathway). It is needed for the catabolism of amino acids (branched-chain ?-keto acid dehydrogenase), phytanic acid and 2-hydroxy straight chain fatty acids (2-hydroxyphytanoyl-CoA lyase)
physiological function
TPK1 is post-transcriptionally upregulated in cancer cells following hypoxic exposure. TPK1 expression is also adaptively upregulated following alterations of redox status by chemotherapeutic and antioxidant treatments. Despite upregulation by hypoxia, intracellular TPP levels are reduced. This loss was reversed by treatment with cell-permeable antioxidants and corresponds with reduced ROS production and enhanced cellular proliferation during supplemental thiamine conditions. siRNA-mediated knockdown of TPK1 directly enhances basal ROS levels and reduces tumor cell proliferation
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). TPK1_HUMAN
243
0
27265
Swiss-Prot
other Location (Reliability: 2)
A0A090N8Y0_HUMAN
243
0
27265
TrEMBL
other Location (Reliability: 2)
B3KRJ6_HUMAN
126
0
13714
TrEMBL
other Location (Reliability: 4)
Q6ZQX6_HUMAN
189
0
20998
TrEMBL
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D133N
mutation causes a selective decrease in the ratio of turnover-number to Km-value for thiamine
D222H
naturally occurring homozygous TPK1 mutation in a patient with enzyme deficiency suffering neurological disorder
Q96E
mutation causes an 2.5fold increase in the ratio of turnover-number to Km-value for thiamine compared to the wild-type
R131G
mutation decreases the ratio of turnover-number to Km-value for ATP
S160L
naturally occurring homozygous TPK1 mutation in a patient with enzyme deficiency suffering neurological disorder. Early thiamine supplementation prevents encephalopathic episodes and improved developmental progression of Patient 1, emphasizing the importance of early diagnosis and treatment of TPK deficiency. The p.Ser160Leu mutation is predicted to interferewith TPK dimerization, which may be another mechanism for the disease
S74A
mutation causes a 1.4fold increase in turnover number, the Km-value for ATP is 2fold that of the wild-type enzyme
additional information
-
three common intronic variants in the maternal and fetal thiamine pyrophosphokinase gene (TPK1) are associated with birth weight, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3)pLysS by cobalt affinity chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
Escherichia coli strain KL21 (DE3)pLysS is transformed with the expression vector coding for a histidine-tagged wild-type or mutant hTPK1
gene TPK1, TPK1 Sanger sequencing analysis, recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)pLysS
TPK1 gene, located in 7q34-36, genotyping in 964 individuals from 220 families of European ancestry revealing an association between maternal rs228584 genotype and offspring birth weight
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
TPK1 is post-transcriptionally upregulated in cancer cells following hypoxic exposure. TPK1 expression is also adaptively upregulated following alterations of redox status by chemotherapeutic and antioxidant treatments. Despite upregulation by hypoxia, intracellular TPP levels are reduced. This loss was reversed by treatment with cell-permeable antioxidants and corresponds with reduced ROS production and enhanced cellular proliferation during supplemental thiamine conditions. siRNA-mediated knockdown of TPK1 directly enhances basal ROS levels and reduces tumor cell proliferation
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Onozuka, M.; Nosaka, K.
Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase
J. Nutr. Sci. Vitaminol.
49
156-162
2003
Homo sapiens (Q9H3S4), Homo sapiens
Zhao, R.; Gao, F.; Goldman, I.D.
Molecular cloning of human thiamin pyrophosphokinase
Biochim. Biophys. Acta
1517
320-322
2001
Homo sapiens (Q9H3S4), Homo sapiens
Fradin, D.; Bougneres, P.
Three common intronic variants in the maternal and fetal thiamine pyrophosphokinase gene (TPK1) are associated with birth weight
Ann. Hum. Genet.
71
578-585
2007
Homo sapiens
Krautwald, M.; Leech, D.; Horne, S.; Steele, M.L.; Forbes, J.; Rahmadi, A.; Griffith, R.; Muench, G.
The advanced glycation end product-lowering agent ALT-711 is a low-affinity inhibitor of thiamine diphosphokinase
Rejuvenation Res.
14
383-391
2011
Homo sapiens
Banka, S.; de Goede, C.; Yue, W.W.; Morris, A.A.; von Bremen, B.; Chandler, K.E.; Feichtinger, R.G.; Hart, C.; Khan, N.; Lunzer, V.; Matakovi?, L.; Marquardt, T.; Makowski, C.; Prokisch, H.; Debus, O.; Nosaka, K.; Sonwalkar, H.; Zimmermann, F.A.; Sperl, W.; Mayr, J.A.
Expanding the clinical and molecular spectrum of thiamine pyrophosphokinase deficiency: a treatable neurological disorder caused by TPK1 mutations
Mol. Genet. Metab.
113
301-306
2014
Homo sapiens (Q9H3S4), Homo sapiens
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