Property Summary

NCBI Gene PubMed Count 40
PubMed Score 4.61
PubTator Score 111.05

Knowledge Summary

Patent (188,631)

Expression

  Differential Expression (12)

Disease log2 FC p
pancreatic cancer 1.100 2.0e-03
malignant mesothelioma -2.200 6.1e-08
psoriasis -3.200 3.1e-05
osteosarcoma -2.702 1.6e-07
medulloblastoma -1.200 2.9e-04
medulloblastoma, large-cell -1.800 1.4e-04
primitive neuroectodermal tumor -1.100 1.4e-02
lung cancer -1.200 2.0e-03
pancreatic carcinoma 1.100 2.0e-03
subependymal giant cell astrocytoma 1.226 7.8e-03
invasive ductal carcinoma -1.500 4.6e-03
ovarian cancer 1.500 2.5e-03

Gene RIF (27)

PMID Text
25948719 Severe deficiency of thymidine kinase 2 was associated with patients with mild forms of myopathy.
25215937 Data indicate that the thymidine kinase 2 enzyme kinetics of thymidine (dT) phosphorylation exhibits negative cooperativity, but deoxycytidine (dC) phosphorylation follows hyperbolic Michaelis-Menten kinetics.
24940680 thymidine kinase 2 but not deoxyguanosine kinase is up-regulated during the stationary growth phase of cultured cells
24455740 We suggest that a chip including DPYD, TYMS, TYMP, TK1, and TK2 genes is a potential tool to predict response in LARC following fluoropyrimidine-based CCRT.
24198295 Thymidine kinase-2 mutations causing mtDNA deletions are linked to a case of late-onset respiratory failure.
23932787 Clinically, hypotonia and proximal muscle weakness are the major phenotypes present in all subjects. In summary, our study expands the molecular and clinical spectrum associated with TK2 deficiency.
22661713 Results strongly suggest that oxidative damage-induced S-glutathionylation and degradation of TK2 have significant impact on mitochondrial DNA precursor synthesis.
21937588 R225W and T230A mutation of TK2 leads to a significant reduction activity in autosomal recessive progressive external ophthalmoplegia patients.
21382338 TK2-deficient cells showed severe mtDNA depletion.
20877624 Observational study of gene-disease association. (HuGE Navigator)
20237496 Observational study of gene-disease association. (HuGE Navigator)
19736010 Sequence analysis of the TK2 gene revealed two novel heterozygous mutations: the frame shift mutation, c.255_c.258delAGAA, and the heterozygous missense mutation, c.515G>A, (p.R172Q).
19265691 Gene mutations in TK2 resulting in MDS syndrome was studied.
19154348 Normal fibroblasts apparently contain more TK2 than needed to maintain dTTP during quiescence, which would explain why TK2-mutated fibroblasts do not manifest mtDNA depletion despite their reduced TK2 activity.
18508266 Novel mutations(p.Q87X and p.N100S) in the TK2 gene associated with fatal mitochondrial DNA depletion myopathy.
18446447 Mutations in TK2, necessary for mtDNA biogenesis, increased risk for defective mtDNA replication, leading to LV hypertrophy.
18265975 FMAU is preferably phosphorylated by TK2 and can track TK2 activity and mitochondrial mass in cellular stress. FMAU may provide an early marker of treatment effects.
18021809 A 12-year-old patient with mitochondrial DNA (mtDNA) depletion syndrome due to TK2 gene mutations has been evaluated serially over the last 10 years. We observed progressive muscle atrophy with selective loss of type 2 muscle fibers.
17913703 activity of TK2 is curbed by thymidine phosphorylase, which degrades thymidine in the cytoplasm, thus limiting the availability of thymidine for phosphorylation by TK2 in mitochondria
17468435 Using (124)I-FIAU, (18)F-FIAU, or (18)F-FEAU, it should be possible to image DeltahTK2 reporter gene expression with PET in preclinical and clinical studies.
17065084 import of cytosolic dNTPs in mitochondria of proliferating cells can compensate a TK2 induced imbalance of the mitochondrial dNTP pool
16969512 an increase in activity of dCK, TK1 and 2 might be involved in an adaptive response of cultured human squamous lung carcinoma cells to radiation by facilitation of DNA repair
14659972 Long-term treatment of H9 human lymphoid cells in the presence of dideoxycytidine down-regulated TK2 gene expression and reduced the expression and activity of TK in resistant cells.
12873860 exon 5 is a "hot spot" for TK2 mutations in patients with myopathic mitochondrial DNA depletion syndrome
12682338 TK2 deficiency associated with myopathy and apparent reversion of mtDNA depletion noted in a 14-year-old patient in whom pathogenic mutations were identified in the TK2 gene
12493767 human thymidine kinase 2 has a role in mitochondrial DNA depletion myopathy as demonstrated by kinetic analysis
12391347 TK2 mutations have been identified in four patients from two families with myopathic mitochondrial DNA depletion and spinal muscular atrophy.

AA Sequence

MLLWPLRGWAARALRCFGPGSRGSPASGPGPRRVQRRAWPPDKEQEKEKKSVICVEGNIASGKTTCLEFF      1 - 70
SNATDVEVLTEPVSKWRNVRGHNPLGLMYHDASRWGLTLQTYVQLTMLDRHTRPQVSSVRLMERSIHSAR     71 - 140
YIFVENLYRSGKMPEVDYVVLSEWFDWILRNMDVSVDLIVYLRTNPETCYQRLKKRCREEEKVIPLEYLE    141 - 210
AIHHLHEEWLIKGSLFPMAAPVLVIEADHHMERMLELFEQNRDRILTPENRKHCP                   211 - 265
//

Text Mined References (43)

PMID Year Title
25948719 2015 Severe TK2 enzyme activity deficiency in patients with mild forms of myopathy.
25944712 2015 N-terminome analysis of the human mitochondrial proteome.
25446393 2015 Clinical application of whole exome sequencing reveals a novel compound heterozygous TK2-mutation in two brothers with rapidly progressive combined muscle-brain atrophy, axonal neuropathy, and status epilepticus.
25215937 2014 Thymidine kinase 2 enzyme kinetics elucidate the mechanism of thymidine-induced mitochondrial DNA depletion.
24940680 2014 Mitochondrial thymidine kinase 2 but not deoxyguanosine kinase is up-regulated during the stationary growth phase of cultured cells.
24455740 2013 DPYD, TYMS, TYMP, TK1, and TK2 genetic expressions as response markers in locally advanced rectal cancer patients treated with fluoropyrimidine-based chemoradiotherapy.
24198295 2013 Late-onset respiratory failure due to TK2 mutations causing multiple mtDNA deletions.
23932787 Molecular and clinical characterization of the myopathic form of mitochondrial DNA depletion syndrome caused by mutations in the thymidine kinase (TK2) gene.
22661713 2012 Oxidative stress induced S-glutathionylation and proteolytic degradation of mitochondrial thymidine kinase 2.
21937588 2012 Thymidine kinase 2 mutations in autosomal recessive progressive external ophthalmoplegia with multiple mitochondrial DNA deletions.
21382338 2011 Targeted impairment of thymidine kinase 2 expression in cells induces mitochondrial DNA depletion and reveals molecular mechanisms of compensation of mitochondrial respiratory activity.
20877624 2010 Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
20237496 2010 New genetic associations detected in a host response study to hepatitis B vaccine.
19878914 2009 Spinocerebellar ataxia type 31 is associated with "inserted" penta-nucleotide repeats containing (TGGAA)n.
19736010 2009 Progressive myofiber loss with extensive fibro-fatty replacement in a child with mitochondrial DNA depletion syndrome and novel thymidine kinase 2 gene mutations.
19265691 2009 Altered gene transcription profiles in fibroblasts harboring either TK2 or DGUOK mutations indicate compensatory mechanisms.
19154348 2009 Unchanged thymidine triphosphate pools and thymidine metabolism in two lines of thymidine kinase 2-mutated fibroblasts.
18508266 2008 Novel mutations in the TK2 gene associated with fatal mitochondrial DNA depletion myopathy.
18446447 2008 Cardiac-targeted transgenic mutant mitochondrial enzymes: mtDNA defects, antiretroviral toxicity and cardiomyopathy.
18265975 2008 Tracking cellular stress with labeled FMAU reflects changes in mitochondrial TK2.
18021809 2008 Selective muscle fiber loss and molecular compensation in mitochondrial myopathy due to TK2 deficiency.
17913703 2007 Mitochondrial thymidine kinase and the enzymatic network regulating thymidine triphosphate pools in cultured human cells.
17468435 2007 A human-derived reporter gene for noninvasive imaging in humans: mitochondrial thymidine kinase type 2.
17065084 2006 The role of mitochondrial dNTP levels in cells with reduced TK2 activity.
16969512 2006 Time course of enhanced activity of deoxycytidine kinase and thymidine kinase 1 and 2 in cultured human squamous lung carcinoma cells, SW-1573, induced by gamma-irradiation.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
15907288 2005 Novel mutations in the thymidine kinase 2 gene (TK2) associated with fatal mitochondrial myopathy and mitochondrial DNA depletion.
15639197 2005 Molecular insight into mitochondrial DNA depletion syndrome in two patients with novel mutations in the deoxyguanosine kinase and thymidine kinase 2 genes.
15616553 2004 The sequence and analysis of duplication-rich human chromosome 16.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14659972 2004 2', 3'-Dideoxycytidine represses thymidine kinases 1 and 2 expression in T-lymphoid cells.
12873860 2003 Mitochondrial myopathy of childhood associated with mitochondrial DNA depletion and a homozygous mutation (T77M) in the TK2 gene.
12687391 2003 Spinal muscular atrophy and mitochondrial DNA depletion. Response to Berber et al. (2003) Acta Neuropathol 105:245-251.
12682338 2003 Reversion of mtDNA depletion in a patient with TK2 deficiency.
12493767 2003 Kinetic properties of mutant human thymidine kinase 2 suggest a mechanism for mitochondrial DNA depletion myopathy.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12391347 2002 Mitochondrial DNA depletion: mutations in thymidine kinase gene with myopathy and SMA.
11687801 2001 Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy.
9989599 1999 Human thymidine kinase 2: molecular cloning and characterisation of the enzyme activity with antiviral and cytostatic nucleoside substrates.
9598140 1998 Substrate/inhibitor specificities of human deoxycytidine kinase (dCK) and thymidine kinases (TK1 and TK2).
9079672 1997 Cloning of the cDNA and chromosome localization of the gene for human thymidine kinase 2.
1597187 1992 Mammalian thymidine kinase 2. Direct photoaffinity labeling with [32P]dTTP of the enzyme from spleen, liver, heart and brain.
605384 1977 Human mitochondrial thymidine kinase is coded for by a gene on chromosome 16 of the nucleus.