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Aliases for TK2 Gene

Aliases for TK2 Gene

  • Thymidine Kinase 2, Mitochondrial 2 3 5
  • Mt-TK 3 4
  • Thymidine Kinase 2 3
  • EC 2.7.1.21 4
  • MTDPS2 3
  • SCA31 3
  • PEOB3 3
  • MTTK 3

External Ids for TK2 Gene

Previous GeneCards Identifiers for TK2 Gene

  • GC16M057239
  • GC16M066921
  • GC16M066280
  • GC16M066320
  • GC16M065102
  • GC16M066543
  • GC16M052417
  • GC16M066505
  • GC16M066506

Summaries for TK2 Gene

Entrez Gene Summary for TK2 Gene

  • This gene encodes a deoxyribonucleoside kinase that specifically phosphorylates thymidine, deoxycytidine, and deoxyuridine. The encoded enzyme localizes to the mitochondria and is required for mitochondrial DNA synthesis. Mutations in this gene are associated with a myopathic form of mitochondrial DNA depletion syndrome. Alternate splicing results in multiple transcript variants encoding distinct isoforms, some of which lack transit peptide, so are not localized to mitochondria. [provided by RefSeq, Dec 2012]

GeneCards Summary for TK2 Gene

TK2 (Thymidine Kinase 2, Mitochondrial) is a Protein Coding gene. Diseases associated with TK2 include Mitochondrial Dna Depletion Syndrome 2 and Progressive External Ophthalmoplegia With Mitochondrial Dna Deletions, Autosomal Recessive 3. Among its related pathways are Pyrimidine metabolism and Porphyrin and chlorophyll metabolism. GO annotations related to this gene include nucleoside kinase activity and thymidine kinase activity. An important paralog of this gene is DCK.

UniProtKB/Swiss-Prot for TK2 Gene

  • Phosphorylates thymidine, deoxycytidine, and deoxyuridine in the mitochondrial matrix. In non-replicating cells, where cytosolic dNTP synthesis is down-regulated, mtDNA synthesis depends solely on TK2 and DGUOK. Widely used as target of antiviral and chemotherapeutic agents.

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TK2 Gene

Genomics for TK2 Gene

Regulatory Elements for TK2 Gene

Enhancers for TK2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH16G066515 2.1 FANTOM5 Ensembl ENCODE dbSUPER 31.2 +31.3 31321 12.4 CREB3L1 MLX ZFP64 DMAP1 YY1 SLC30A9 ZNF143 ZNF416 ZNF548 ZNF263 TK2 CKLF E2F4 KIAA0895L BEAN1 ZDHHC1 CKLF-CMTM1 ENSG00000260465 CMTM2 PLEKHG4
GH16G066502 1.6 FANTOM5 Ensembl ENCODE dbSUPER 28.7 +49.8 49780 1.2 ELF3 SAP130 ZNF384 CEBPG RAD21 RARA YY1 ZNF366 THAP11 GATAD2A TK2 CKLF CKLF-CMTM1 CES3 ENSG00000260755 GC16P066491
GH16G066547 1.4 ENCODE dbSUPER 29.9 +1.5 1494 6.6 MLX CREB3L1 ZFP64 DMAP1 YY1 SLC30A9 ZNF416 ZNF143 ZNF263 SP3 TK2 BEAN1 BEAN1-AS1 E2F4 KIAA0895L PLEKHG4 CMTM2 ENSG00000260465 ZDHHC1 FBXL8
GH16G066510 1.5 Ensembl ENCODE dbSUPER 22.9 +40.4 40377 3.8 PKNOX1 FOXA2 ARID4B SIN3A TCF12 ZNF121 GATA2 ELK1 FOS SP5 BEAN1 TK2 BEAN1-AS1 CKLF CKLF-CMTM1 CMTM2 CES4A GC16M066512 ENSG00000260851
GH16G066603 1.1 ENCODE 19.5 -52.3 -52331 3.6 HDGF PKNOX1 FOXA2 MLX ARNT ARID4B DMAP1 ZNF766 KLF13 SP3 TK2 BEAN1 CMTM3 CES2 CMTM4 GC16M066618 PIR36038
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around TK2 on UCSC Golden Path with GeneCards custom track

Promoters for TK2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000281240 512 1001 HDGF HNRNPUL1 SIN3A DMAP1 ZNF48 YY1 ZNF766 GLIS2 ELK1 ZNF143

Genomic Location for TK2 Gene

Chromosome:
16
Start:
66,508,003 bp from pter
End:
66,552,544 bp from pter
Size:
44,542 bases
Orientation:
Minus strand

Genomic View for TK2 Gene

Genes around TK2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TK2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TK2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TK2 Gene

Proteins for TK2 Gene

  • Protein details for TK2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O00142-KITM_HUMAN
    Recommended name:
    Thymidine kinase 2, mitochondrial
    Protein Accession:
    O00142
    Secondary Accessions:
    • B4DGJ7
    • B4DZK7
    • B7ZAB1
    • E5KNQ5
    • E9PH08
    • O15238

    Protein attributes for TK2 Gene

    Size:
    265 amino acids
    Molecular mass:
    31005 Da
    Quaternary structure:
    • Monomer.

    Alternative splice isoforms for TK2 Gene

neXtProt entry for TK2 Gene

Post-translational modifications for TK2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for TK2 Gene

Domains & Families for TK2 Gene

Protein Domains for TK2 Gene

Graphical View of Domain Structure for InterPro Entry

O00142

UniProtKB/Swiss-Prot:

KITM_HUMAN :
  • Belongs to the DCK/DGK family.
Family:
  • Belongs to the DCK/DGK family.
genes like me logo Genes that share domains with TK2: view

No data available for Gene Families for TK2 Gene

Function for TK2 Gene

Molecular function for TK2 Gene

GENATLAS Biochemistry:
thymidine kinase 2,pyrimidine salvage pathway,mitochondrial,involved in the activation of chemotherapeutic nucleoside analogues
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + thymidine = ADP + thymidine 5-phosphate.
UniProtKB/Swiss-Prot Function:
Phosphorylates thymidine, deoxycytidine, and deoxyuridine in the mitochondrial matrix. In non-replicating cells, where cytosolic dNTP synthesis is down-regulated, mtDNA synthesis depends solely on TK2 and DGUOK. Widely used as target of antiviral and chemotherapeutic agents.

Enzyme Numbers (IUBMB) for TK2 Gene

Gene Ontology (GO) - Molecular Function for TK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004137 deoxycytidine kinase activity IEA --
GO:0004797 thymidine kinase activity IEA --
GO:0005524 ATP binding IEA --
GO:0016301 kinase activity IEA --
GO:0016740 transferase activity IEA --
genes like me logo Genes that share ontologies with TK2: view
genes like me logo Genes that share phenotypes with TK2: view

Human Phenotype Ontology for TK2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TK2 Gene

MGI Knock Outs for TK2:

Animal Model Products

CRISPR Products

miRNA for TK2 Gene

miRTarBase miRNAs that target TK2

Inhibitory RNA Products

No data available for Transcription Factor Targets and HOMER Transcription for TK2 Gene

Localization for TK2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TK2 Gene

Mitochondrion.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TK2 gene
Compartment Confidence
mitochondrion 5
peroxisome 2
cytosol 2

Gene Ontology (GO) - Cellular Components for TK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IEA --
GO:0005759 mitochondrial matrix TAS --
genes like me logo Genes that share ontologies with TK2: view

Pathways & Interactions for TK2 Gene

genes like me logo Genes that share pathways with TK2: view

Gene Ontology (GO) - Biological Process for TK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006139 nucleobase-containing compound metabolic process IEA,TAS 9079672
GO:0009157 deoxyribonucleoside monophosphate biosynthetic process IEA --
GO:0009165 nucleotide biosynthetic process IEA --
GO:0016310 phosphorylation IEA --
GO:0043097 pyrimidine nucleoside salvage TAS --
genes like me logo Genes that share ontologies with TK2: view

No data available for SIGNOR curated interactions for TK2 Gene

Drugs & Compounds for TK2 Gene

(14) Drugs for TK2 Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Floxuridine Approved Pharma Antineoplastic antimetabolite, RNA and DNA synthesis inhibitor 49
Adenosine triphosphate Approved Nutra 0
thymidine Experimental Pharma Target 0
deoxycytidine Experimental Pharma Target 0
Deoxyuridine Experimental Pharma 5

(20) Additional Compounds for TK2 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
5-Fluorodeoxyuridine monophosphate
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
dUMP
  • 2'-Deoxy-5'-uridylate
  • 2'-Deoxy-5'-uridylic acid
  • 2'-Deoxyuridine 5'-monophosphate
  • 2'-Deoxyuridine 5'-phosphate
  • 2'-Deoxyuridylate
964-26-1
genes like me logo Genes that share compounds with TK2: view

Transcripts for TK2 Gene

Unigene Clusters for TK2 Gene

Thymidine kinase 2, mitochondrial:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Alternative Splicing Database (ASD) splice patterns (SP) for TK2 Gene

No ASD Table

Relevant External Links for TK2 Gene

GeneLoc Exon Structure for
TK2
ECgene alternative splicing isoforms for
TK2

Expression for TK2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for TK2 Gene

Protein differential expression in normal tissues from HIPED for TK2 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (7.3) and Skin (6.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for TK2 Gene



Protein tissue co-expression partners for TK2 Gene

NURSA nuclear receptor signaling pathways regulating expression of TK2 Gene:

TK2

SOURCE GeneReport for Unigene cluster for TK2 Gene:

Hs.512619

mRNA Expression by UniProt/SwissProt for TK2 Gene:

O00142-KITM_HUMAN
Tissue specificity: Predominantly expressed in liver, pancreas, muscle, and brain.

Evidence on tissue expression from TISSUES for TK2 Gene

  • Nervous system(4.7)
  • Liver(4.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for TK2 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Organs:
Head and neck:
  • brain
  • cerebellum
  • cerebrospinal fluid
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • head
  • larynx
  • meninges
  • mouth
  • neck
  • pharynx
  • vocal cord
Thorax:
  • esophagus
  • heart
  • heart valve
  • lung
Abdomen:
  • kidney
  • stomach
Limb:
  • arm
  • digit
  • foot
  • forearm
  • lower limb
  • shin
  • thigh
  • upper limb
General:
  • blood
  • blood vessel
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal cord
genes like me logo Genes that share expression patterns with TK2: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for TK2 Gene

Orthologs for TK2 Gene

This gene was present in the common ancestor of animals.

Orthologs for TK2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia TK2 34 35
  • 99.37 (n)
dog
(Canis familiaris)
Mammalia TK2 34 35
  • 87.95 (n)
cow
(Bos Taurus)
Mammalia TK2 34 35
  • 84.99 (n)
mouse
(Mus musculus)
Mammalia Tk2 34 16 35
  • 83.02 (n)
rat
(Rattus norvegicus)
Mammalia Tk2 34
  • 83.02 (n)
oppossum
(Monodelphis domestica)
Mammalia TK2 35
  • 76 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia TK2 35
  • 69 (a)
OneToOne
chicken
(Gallus gallus)
Aves TK2 34 35
  • 73.09 (n)
lizard
(Anolis carolinensis)
Reptilia -- 35
  • 72 (a)
OneToMany
-- 35
  • 70 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia tk2 34
  • 69.33 (n)
Str.424 34
African clawed frog
(Xenopus laevis)
Amphibia LOC398276 34
zebrafish
(Danio rerio)
Actinopterygii tk2 34 35
  • 68.95 (n)
Dr.18401 34
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP001585 34
  • 56.35 (n)
fruit fly
(Drosophila melanogaster)
Insecta dnk 36 34 35
  • 51.14 (n)
Species where no ortholog for TK2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for TK2 Gene

ENSEMBL:
Gene Tree for TK2 (if available)
TreeFam:
Gene Tree for TK2 (if available)

Paralogs for TK2 Gene

Paralogs for TK2 Gene

genes like me logo Genes that share paralogs with TK2: view

Variants for TK2 Gene

Sequence variations from dbSNP and Humsavar for TK2 Gene

SNP ID Clin Chr 16 pos Sequence Context AA Info Type
rs137854429 Pathogenic, Mitochondrial DNA depletion syndrome 2 (MTDPS2) [MIM:609560] 66,531,394(-) ACAGG(A/C)ATACT nc-transcript-variant, reference, missense
rs137854430 Pathogenic, Mitochondrial DNA depletion syndrome 2 (MTDPS2) [MIM:609560] 66,513,795(-) AGCAA(A/T)TCACC nc-transcript-variant, reference, missense
rs137854431 Pathogenic, Mitochondrial DNA depletion syndrome 2 (MTDPS2) [MIM:609560] 66,531,432(-) TCTTA(C/T)GCTAC nc-transcript-variant, reference, missense
rs137854432 Pathogenic, Mitochondrial DNA depletion syndrome 2 (MTDPS2) [MIM:609560] 66,541,951(-) CAGAT(C/G)TGTGT intron-variant, nc-transcript-variant, reference, missense, utr-variant-5-prime
rs137886900 Pathogenic, Mitochondrial DNA depletion syndrome 2 (MTDPS2) [MIM:609560], Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3 (PEOB3) [MIM:617069] 66,517,207(+) GGTCC(A/C/G/T)AAGGT intron-variant, nc-transcript-variant, reference, synonymous-codon, missense

Structural Variations from Database of Genomic Variants (DGV) for TK2 Gene

Variant ID Type Subtype PubMed ID
esv2676087 CNV deletion 23128226
nsv1839 CNV insertion 18451855

Variation tolerance for TK2 Gene

Residual Variation Intolerance Score: 52.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.24; 76.25% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for TK2 Gene

Human Gene Mutation Database (HGMD)
TK2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TK2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TK2 Gene

Disorders for TK2 Gene

MalaCards: The human disease database

(9) MalaCards diseases for TK2 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
mitochondrial dna depletion syndrome 2
  • mitochondrial dna depletion syndrome, myopathic form
progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 3
  • progressive external ophthalmoplegia, autosomal recessive 3
progressive external ophthalmoplegia, autosomal recessive 1
  • kearns-sayre syndrome
tk2-related mitochondrial dna depletion syndrome, myopathic form
  • mitochondrial dna depletion syndrome 2
mitochondrial dna depletion syndrome, myopathic form
- elite association - COSMIC cancer census association via MalaCards
Search TK2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

KITM_HUMAN
  • Mitochondrial DNA depletion syndrome 2 (MTDPS2) [MIM:609560]: A disorder due to mitochondrial dysfunction characterized by childhood onset of muscle weakness associated with depletion of mtDNA in skeletal muscle. There is wide clinical variability; some patients have onset in infancy and show a rapidly progressive course with early death due to respiratory failure, whereas others have later onset of a slowly progressive myopathy. {ECO:0000269 PubMed:11687801, ECO:0000269 PubMed:12391347, ECO:0000269 PubMed:15639197, ECO:0000269 PubMed:15907288, ECO:0000269 PubMed:25446393}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3 (PEOB3) [MIM:617069]: A form of progressive external ophthalmoplegia, a mitochondrial myopathy characterized by progressive paralysis of the levator palpebrae, orbicularis oculi, and extraocular muscles. PEOB3 patients manifest adult-onset progressive external ophthalmoplegia and progressive proximal muscle weakness associated with muscle atrophy. {ECO:0000269 PubMed:21937588}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for TK2

Genetic Association Database (GAD)
TK2
Human Genome Epidemiology (HuGE) Navigator
TK2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
TK2
genes like me logo Genes that share disorders with TK2: view

No data available for Genatlas for TK2 Gene

Publications for TK2 Gene

  1. Molecular insight into mitochondrial DNA depletion syndrome in two patients with novel mutations in the deoxyguanosine kinase and thymidine kinase 2 genes. (PMID: 15639197) Wang L. … Eriksson S. (Mol. Genet. Metab. 2005) 3 4 22 64
  2. Novel mutations in the thymidine kinase 2 gene (TK2) associated with fatal mitochondrial myopathy and mitochondrial DNA depletion. (PMID: 15907288) Tulinius M. … Oldfors A. (Neuromuscul. Disord. 2005) 3 4 22 64
  3. Mitochondrial myopathy of childhood associated with mitochondrial DNA depletion and a homozygous mutation (T77M) in the TK2 gene. (PMID: 12873860) Mancuso M. … DiMauro S. (Arch. Neurol. 2003) 3 22 46 64
  4. Mitochondrial DNA depletion: mutations in thymidine kinase gene with myopathy and SMA. (PMID: 12391347) Mancuso M. … Vu T.H. (Neurology 2002) 3 4 22 64
  5. Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. (PMID: 11687801) Saada A. … Elpeleg O. (Nat. Genet. 2001) 3 4 22 64

Products for TK2 Gene

Sources for TK2 Gene

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