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    TK2 thymidine kinase 2 [ Homo sapiens (human) ]

    Gene ID: 7084, updated on 5-Mar-2024

    Summary

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    Official Symbol
    TK2provided by HGNC
    Official Full Name
    thymidine kinase 2provided by HGNC
    Primary source
    HGNC:HGNC:11831
    See related
    Ensembl:ENSG00000166548 MIM:188250; AllianceGenome:HGNC:11831
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MTTK; PEOB3; SCA31; MTDPS2; TK2-EXT
    Summary
    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]
    Expression
    Ubiquitous expression in fat (RPKM 14.4), testis (RPKM 9.6) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    16q21
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (66508003..66550291, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (72302296..72344586, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (66541906..66584194, complement)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene brain expressed associated with NEDD4 1 Neighboring gene nuclear envelope phosphatase-regulatory subunit 1-like Neighboring gene uncharacterized LOC124903698 Neighboring gene BEAN1 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7558 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:66510981-66511522 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:66512063-66512603 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:66513685-66514224 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:66518060-66519040 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:66521703-66522203 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:66543229-66544204 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:66545181-66546156 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:66546157-66547132 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:66553931-66554431 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10938 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10939 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10940 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7560 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10941 Neighboring gene CKLF-CMTM1 readthrough Neighboring gene chemokine like factor Neighboring gene CKLF like MARVEL transmembrane domain containing 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Metrics of progression and prognosis in untreated adults with thymidine kinase 2 deficiency: An observational study. Domínguez-González C, et al. Neuromuscul Disord, 2022 Sep. PMID 35907766
    2. Mutational analyses of human thymidine kinase 2 reveal key residues in ATP-Mg(2+) binding and catalysis. Wang L, et al. Nucleosides Nucleotides Nucleic Acids, 2022. PMID 34758700
    3. Clinical and molecular spectrum of thymidine kinase 2-related mtDNA maintenance defect. Wang J, et al. Mol Genet Metab, 2018 Jun. PMID 29735374
    4. Retrospective natural history of thymidine kinase 2 deficiency. Garone C, et al. J Med Genet, 2018 Aug. PMID 29602790, Free PMC Article
    5. Pigmentary retinopathy, rod-cone dysfunction and sensorineural deafness associated with a rare mitochondrial tRNA(Lys) (m.8340G>A) gene variant. Gill JS, et al. Br J Ophthalmol, 2017 Sep. PMID 28729369, Free PMC Article

    See all (55) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Thymidine Kinase 2 and Mitochondrial Protein COX I in the Cerebellum of Patients with Spinocerebellar Ataxia Type 31 Caused by Penta-nucleotide Repeats (TTCCA)n.
      Title: Thymidine Kinase 2 and Mitochondrial Protein COX I in the Cerebellum of Patients with Spinocerebellar Ataxia Type 31 Caused by Penta-nucleotide Repeats (TTCCA)(n).
    2. Metrics of progression and prognosis in untreated adults with thymidine kinase 2 deficiency: An observational study.
      Title: Metrics of progression and prognosis in untreated adults with thymidine kinase 2 deficiency: An observational study.
    3. Mutational analyses of human thymidine kinase 2 reveal key residues in ATP-Mg(2+) binding and catalysis.
      Title: Mutational analyses of human thymidine kinase 2 reveal key residues in ATP-Mg(2+) binding and catalysis.
    4. In TK2 deficiency, age at onset, rate of weakness progression and POS are important variables that define three clinical subtypes. Nervous system involvement often complicates the clinical course of the infantile-onset form while extraocular muscle and facial involvement are characteristic of the late-onset form.
      Title: Retrospective natural history of thymidine kinase 2 deficiency.
    5. Thymidine Kinase 2 mutation is associated with myopathic form of mitochondrial DNA maintenance defect.
      Title: Clinical and molecular spectrum of thymidine kinase 2-related mtDNA maintenance defect.
    6. We confirm the pathogenicity of the rare mitochondrial m.8340G>A variant the basis of single-fibre segregation studies and its association with an expanded clinical phenotype. Our case expands the phenotypic spectrum of diseases associated with mitochondrial tRNA point mutations, highlighting the importance of considering a mitochondrial diagnosis.
      Title: Pigmentary retinopathy, rod-cone dysfunction and sensorineural deafness associated with a rare mitochondrial tRNA(Lys) (m.8340G>A) gene variant.
    7. Severe deficiency of thymidine kinase 2 was associated with patients with mild forms of myopathy.
      Title: Severe TK2 enzyme activity deficiency in patients with mild forms of myopathy.
    8. 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.
      Title: Thymidine kinase 2 enzyme kinetics elucidate the mechanism of thymidine-induced mitochondrial DNA depletion.
    9. thymidine kinase 2 but not deoxyguanosine kinase is up-regulated during the stationary growth phase of cultured cells
      Title: Mitochondrial thymidine kinase 2 but not deoxyguanosine kinase is up-regulated during the stationary growth phase of cultured cells.
    10. 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.
      Title: DPYD, TYMS, TYMP, TK1, and TK2 genetic expressions as response markers in locally advanced rectal cancer patients treated with fluoropyrimidine-based chemoradiotherapy.
    Submit: New GeneRIF Correction See all GeneRIFs (32)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables deoxycytidine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables deoxynucleoside kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables nucleoside kinase activity TAS
    Traceable Author Statement
    more info
    		  
    enables thymidine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in DNA biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in deoxycytidine metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in deoxyribonucleoside monophosphate biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in nucleobase-containing compound metabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in nucleotide biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in phosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in pyrimidine nucleoside salvage TAS
    Traceable Author Statement
    more info
    		  
    involved_in thymidine metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    thymidine kinase 2, mitochondrial; thymidine kinase 2
    Names
    2'-deoxyuridine kinase TK2
    deoxycytidine kinase TK2
    mitochondrial thymidine kinase
    mt-TK
    NP_001166114.1
    NP_001166115.1
    NP_001166116.1
    NP_001258863.1
    NP_001258864.1
    NP_001258979.1
    NP_004605.4

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_016862.1 RefSeqGene

      Range
      5291..47410
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001172643.1 → NP_001166114.1  thymidine kinase 2 isoform 2

      See identical proteins and their annotated locations for NP_001166114.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) is not localized to mitochondria, and it has a distinct N-terminus and is shorter than isoform 1.
      Source sequence(s)
      AC010542, U77088
      Consensus CDS
      CCDS54018.1
      UniProtKB/TrEMBL
      A4IF54
      Related
      ENSP00000414334.4, ENST00000451102.7
      Conserved Domains (2) summary
      TIGR00041
      Location:22 → 207
      DTMP_kinase; dTMP kinase
      pfam01712
      Location:22 → 234
      dNK; Deoxynucleoside kinase

    2. NM_001172644.2 → NP_001166115.1  thymidine kinase 2, mitochondrial isoform 3 precursor

      See identical proteins and their annotated locations for NP_001166115.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an in-frame exon in the coding region, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
      Source sequence(s)
      AC010542, AF521891, AK295808
      Consensus CDS
      CCDS54016.1
      UniProtKB/TrEMBL
      B4DIW4
      Related
      ENSP00000438143.2, ENST00000545043.6
      Conserved Domains (1) summary
      pfam01712
      Location:52 → 240
      dNK; Deoxynucleoside kinase

    3. NM_001172645.2 → NP_001166116.1  thymidine kinase 2, mitochondrial isoform 4 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an in-frame exon in the coding region, compared to variant 1. The encoded isoform (4) is shorter than isoform 1.
      Source sequence(s)
      AC010542, AK303590
      Consensus CDS
      CCDS54017.1
      UniProtKB/TrEMBL
      B4DIW4
      Related
      ENSP00000407469.5, ENST00000417693.8
      Conserved Domains (1) summary
      pfam01712
      Location:53 → 247
      dNK; Deoxynucleoside kinase

    4. NM_001271934.2 → NP_001258863.1  thymidine kinase 2 isoform 5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) has an additional exon in the 5' region, which results in an alternate translation start codon, compared to variant 1. The encoded isoform (5) is not localized to mitochondria, and it has a distinct N-terminus and is shorter than isoform 1.
      Source sequence(s)
      AC010542, AF521891, AK303590, AL038860, BC142970
      UniProtKB/TrEMBL
      A5PLM0
      Conserved Domains (2) summary
      TIGR00041
      Location:4 → 189
      DTMP_kinase; dTMP kinase
      pfam01712
      Location:4 → 211
      dNK; Deoxynucleoside kinase

    5. NM_001271935.1 → NP_001258864.1  thymidine kinase 2 isoform 6

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) differs in the 5' UTR, lacks a portion of the 5' coding region and two internal exons, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (6) is not localized to mitochondria, and it has a distinct N-terminus, lacks an internal segment and is shorter than isoform 1.
      Source sequence(s)
      AC010542, AL038860, BC113928, BC134344, U77088
      Consensus CDS
      CCDS92169.1
      UniProtKB/TrEMBL
      J3QRP0
      Related
      ENSP00000464313.2, ENST00000569718.6
      Conserved Domains (1) summary
      cl17190
      Location:22 → 121
      NK; Nucleoside/nucleotide kinase (NK) is a protein superfamily consisting of multiple families of enzymes that share structural similarity and are functionally related to the catalysis of the reversible phosphate group transfer from nucleoside triphosphates ...

    6. NM_001272050.2 → NP_001258979.1  thymidine kinase 2, mitochondrial isoform 7 precursor

      See identical proteins and their annotated locations for NP_001258979.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (9) contains an alternate 5' exon and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (7) has a shorter N-terminus, compared to isoform 1, but is predicted to be a mitochondrial protein.
      Source sequence(s)
      AC010542, AK302976, AL038860, BC134344
      Consensus CDS
      CCDS61955.1
      UniProtKB/TrEMBL
      A0A7P0MLU2
      Related
      ENSP00000434594.1, ENST00000525974.5
      Conserved Domains (1) summary
      cl17190
      Location:1 → 163
      NK; Nucleoside/nucleotide kinase (NK) is a protein superfamily consisting of multiple families of enzymes that share structural similarity and are functionally related to the catalysis of the reversible phosphate group transfer from nucleoside triphosphates ...

    7. NM_004614.5 → NP_004605.4  thymidine kinase 2, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_004605.4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC010542, AF521891
      Consensus CDS
      CCDS10805.2
      UniProtKB/Swiss-Prot
      B4DGJ7, B4DZK7, B7ZAB1, E5KNQ5, E9PH08, O00142, O15238
      UniProtKB/TrEMBL
      H3BP77
      Related
      ENSP00000440898.2, ENST00000544898.6
      Conserved Domains (1) summary
      pfam01712
      Location:53 → 265
      dNK; Deoxynucleoside kinase

    RNA

    1. NR_073520.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) lacks a splice junction in the 5' region, which is supported by several transcripts, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC010542, AL038860, BC134344, U80628

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      66508003..66550291 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      72302296..72344586 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NR_073521.1: Suppressed sequence

      Description
      NR_073521.1: This RefSeq was permanently suppressed because it is now thought that this gene does encode a protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O00142.4 GenPept UniProtKB/Swiss-Prot:O00142

    Gene LinkOut

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