Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

2.7.1.21

Official Name

thymidine kinase

Name from literature

thymidine kinase

Pathway from literature

synthesis of dTTP/the salvage pathway of nucleotide metabolism

Pathway from KEGG

Xenobiotics Biodegradation and Metabolism; Drug metabolism - other enzymes; map00983

Nucleotide Metabolism; Pyrimidine metabolism; map00240

Organisms

Human (9606)

Genome localization

17q23.2-q25.3[7083 ], 16q22-q23.1[7084 ],

Comments

Deoxyuridine can also act as acceptor, and dGTP can act as a donor. The deoxypyrimidine kinase complex induced by Herpes simplex virus catalyses this reaction as well as those of EC 2.7.1.114 (AMP---thymidine kinase), EC 2.7.1.118 (ADP---thymidine kinase) and EC 2.7.4.9 (dTMP-kinase).

Rate-limiting Description

"5'-AdThd is a thymidine analogue that at low concentrations (<30 micrometer) can increase thymidine kinase activity, which is the rate-limiting enzyme for activation of IdUrd." (9816259)

Regulatory Information

Upstream transcription factor

7088;7157;10589

Regulatory type

Detail

transcriptional level;

"Heterogeneous nuclear ribonucleoproteins as regulators of gene expression through interactions with the human thymidine kinase promoter." (10972977)

post translational modification;

"The cell cycle specific activity of TK1 is regulated at the transcriptional level, but posttranslational mechanisms seem to play an important role for the level of functional TK1 protein as well." (17065087)

key enzyme;

"Subsequent incubation of the neutral and cationic organometallic 99 mTc thymidine derivatives with human cytosolic thymidine kinase, a key enzyme in tumour proliferation, revealed that only the neutral compounds maintained substrate activity towards the enzyme." (18494020)

phosphorylation;CDK1;CDK2

"Serine 13 is the site of mitotic phosphorylation of human thymidine kinase." (9575153#16964243)

inhibitor;

"The structures of hTK1 and of the Thermotoga maritima thymidine kinase (TmTK) in complex with the bisubstrate inhibitor TP4A, is reported." (17407781)

phosphorylation;

P04183

phosphorylation;

P04183:from_uniprot:13_Phosphoserine

phosphorylation;

P04183:from_uniprot:231_Phosphoserine

transcriptional factor;E2F

"Phosphorylation of the retinoblastoma protein by cyclin-dependent kinases 4 and 6 prevents its interaction with the transcription factor E2F, which subsequently promotes the expression of S phase regulated genes, such as thymidine kinase." (8622883#8723352)

transcriptional factor;

"Temporal regulation of cyclin A-p107 and p33cdk2 complexes binding to a human thymidine kinase promoter element important for G1-S phase transcriptional regulation." (8475104)

interact with TF;DRAP1(10589)

"A human protein-protein interaction network: a resource for annotating the proteome." (16169070)

interact with TF;TLE1(7088)

"A human protein-protein interaction network: a resource for annotating the proteome." (16169070)

interact with TF;TP53(7157)

"A human protein-protein interaction network: a resource for annotating the proteome." (16169070)

Gene ontology

Gene ontology

GO:0006260 (P) DNA replication [P04183, O00142 ];
GO:0016773 (F) phosphotransferase activity, alcohol group ... [O00142 ];
GO:0004797 (F) thymidine kinase activity [P04183, O00142 ];
GO:0005829 (C) cytosol [P04183 ];
GO:0005524 (F) ATP binding [P04183, O00142 ];

Tissue expression

Tissue From HPRD

Nervous system [01770 ];
Mammary gland [01771 ];
Fetus [01771 ];
Ovary [01771 ];
Cervix [01771 ];
Placenta [01770, 01771 ];
Lymphocyte [01771 ];
Brain [01770 ];
Muscle [01770 ];
Spleen [01770 ];

Tissue specificity

Predominantly expressed in liver, pancreas, muscle, and brain [O00142 ];

Subcellular localization

Localization

mitochondrion [O00142 ];

cytoplasm [P04183 ];

Disease relevance

Disease

Defects in TK2 are a cause of myopathic mitochondrial DNA depletion syndrome (MDS) [MIM:609560]. MDS is a clinically heterogeneous group of disorders characterized by a reduction in mitochondrial DNA (mtDNA) copy number. Primary mtDNA depletion is inherited as an autosomal recessive trait and may affect single organs, typically muscle or liver, or multiple tissues. The myopathic form of mtDNA depletion syndrome is a slowly progressive mitochondrial disorder starting in childhood and associated with less severe depletion of mtDNA in skeletal muscle (66 to 86%) compared to the hepatocerebral form of mtDNA depletion syndrome which shows up to 99% mtDNA depletion in liver [O00142 ];

Links

SwissProt

B4DZK7; O00142; P04183

Entrez Gene

7083; 7084

HPRD

01771; 01770



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  Last Modified: 2009-03-24  
  Design by Zhao Min