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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 (KEGG) and Drug metabolism - cytochrome P450. Gene Ontology (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.

Additional gene information for TK2 Gene

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

GeneHancer (GH) Regulatory Elements for TK2 Gene

Promoters and enhancers for TK2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH16I066547 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 580 +1.5 1493 6.6 MLX ZFP64 DMAP1 YY1 SLC30A9 E2F8 ZNF416 ZNF143 SP3 NFYC TK2 ENSG00000275745 PIR54425 PIR51465 ENSG00000261519 CKLF-CMTM1 CKLF NAE1 ZDHHC1 BEAN1
GH16I066515 Enhancer 1.8 FANTOM5 Ensembl ENCODE dbSUPER 31.2 +31.3 31320 12.4 HDGF PKNOX1 FOXA2 SMAD1 MLX ARNT ARID4B SIN3A DMAP1 IRF4 TK2 CKLF ENSG00000260465 ZDHHC1 NAE1 BEAN1 CKLF-CMTM1 E2F4 CMTM2 PLEKHG4
GH16I066502 Enhancer 1.4 FANTOM5 Ensembl ENCODE dbSUPER 28.7 +49.8 49780 1.2 ELF3 RAD21 RARA ETS1 YY1 ZNF366 ATF7 THAP11 RXRA CEBPB TK2 E2F4 CKLF CKLF-CMTM1 ENSG00000260465 CES3 ENSG00000260755 GC16P066491 ENSG00000260851
GH16I066603 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 19.5 -52.3 -52330 3.6 HDGF PKNOX1 FOXA2 ARNT MLX ARID4B SIN3A DMAP1 ZNF766 ZNF143 CMTM3 TK2 BEAN1 ZDHHC1 ENSG00000260465 CTCF NAE1 TRADD FBXL8 CES2
GH16I066510 Enhancer 1.3 Ensembl ENCODE dbSUPER 22.9 +40.4 40377 3.8 PKNOX1 FOXA2 ARID4B SIN3A ETS1 TCF12 ELK1 ATF7 FOS RXRA GC16M066512 PIR55233 PIR49300 BEAN1 TK2 BEAN1-AS1 CKLF CKLF-CMTM1 CMTM2 CES4A
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around TK2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the TK2 gene promoter:

Genomic Locations for TK2 Gene

Genomic Locations for TK2 Gene
chr16:66,508,003-66,552,544
(GRCh38/hg38)
Size:
44,542 bases
Orientation:
Minus strand
chr16:66,541,906-66,586,447
(GRCh37/hg19)

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

No Post-translational modifications

No data available for DME Specific Peptides for TK2 Gene

Domains & Families for TK2 Gene

Gene Families for TK2 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

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

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

Phenotypes From GWAS Catalog 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 TAS,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

Clone 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

No data available for Subcellular locations from the Human Protein Atlas (HPA) for TK2 Gene

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 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

(13) 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 50
thymidine Experimental, Investigational Pharma Target 0
deoxycytidine Experimental, Investigational Pharma Target 0
Deoxyuridine Experimental Pharma 6
Thymidine-5'-Triphosphate Experimental Pharma Target 0

(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

Clone 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
Regions:
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 33 34
  • 99.37 (n)
dog
(Canis familiaris)
Mammalia TK2 33 34
  • 87.95 (n)
cow
(Bos Taurus)
Mammalia TK2 33 34
  • 84.99 (n)
mouse
(Mus musculus)
Mammalia Tk2 33 16 34
  • 83.02 (n)
rat
(Rattus norvegicus)
Mammalia Tk2 33
  • 83.02 (n)
oppossum
(Monodelphis domestica)
Mammalia TK2 34
  • 76 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia TK2 34
  • 69 (a)
OneToOne
chicken
(Gallus gallus)
Aves TK2 33 34
  • 73.09 (n)
lizard
(Anolis carolinensis)
Reptilia -- 34
  • 72 (a)
OneToMany
-- 34
  • 70 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia tk2 33
  • 69.33 (n)
Str.424 33
African clawed frog
(Xenopus laevis)
Amphibia LOC398276 33
zebrafish
(Danio rerio)
Actinopterygii tk2 33 34
  • 68.95 (n)
Dr.18401 33
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP001585 33
  • 56.35 (n)
fruit fly
(Drosophila melanogaster)
Insecta dnk 35 33 34
  • 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 Variation AA Info Type
rs1008957692 uncertain-significance, Mitochondrial DNA depletion syndrome 66,511,047(-) C/T 3_prime_UTR_variant, non_coding_transcript_variant
rs1028511517 uncertain-significance, Mitochondrial DNA depletion syndrome 66,511,373(-) C/T 3_prime_UTR_variant, non_coding_transcript_variant
rs117229729 benign, likely-benign, not specified, Mitochondrial DNA depletion syndrome 66,541,965(-) C/T intron_variant
rs137854429 pathogenic, Mitochondrial DNA depletion syndrome 2, Mitochondrial DNA depletion syndrome 2 (MTDPS2) [MIM:609560] 66,531,394(-) G/T coding_sequence_variant, missense_variant, non_coding_transcript_variant
rs137854430 pathogenic, Mitochondrial DNA depletion syndrome 2, Mitochondrial DNA depletion syndrome 2 (MTDPS2) [MIM:609560] 66,513,795(-) A/T coding_sequence_variant, missense_variant, non_coding_transcript_variant

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

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

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)

Additional Variant Information 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

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

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.

Additional Disease Information for TK2

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

No data available for Genatlas for TK2 Gene

Publications for TK2 Gene

  1. Novel mutations in the thymidine kinase 2 gene (TK2) associated with fatal mitochondrial myopathy and mitochondrial DNA depletion. (PMID: 15907288) Tulinius M … Oldfors A (Neuromuscular disorders : NMD 2005) 3 4 22 58
  2. 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 (Molecular genetics and metabolism 2005) 3 4 22 58
  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 (Archives of neurology 2003) 3 22 44 58
  4. Mitochondrial DNA depletion: mutations in thymidine kinase gene with myopathy and SMA. (PMID: 12391347) Mancuso M … Vu TH (Neurology 2002) 3 4 22 58
  5. Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. (PMID: 11687801) Saada A … Elpeleg O (Nature genetics 2001) 3 4 22 58

Products for TK2 Gene

Sources for TK2 Gene

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