LOCUS       NM_004614               4824 bp    mRNA    linear   PRI 10-OCT-2024
DEFINITION  Homo sapiens thymidine kinase 2 (TK2), transcript variant 1, mRNA;
            nuclear gene for mitochondrial product.
ACCESSION   NM_004614
VERSION     NM_004614.5
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 4824)
  AUTHORS   Aoki,H., Higashi,M., Okita,M., Ando,N., Murayama,S., Ishikawa,K.
            and Yokota,T.
  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
  JOURNAL   Cerebellum 22 (1), 70-84 (2023)
   PUBMED   35084690
  REMARK    GeneRIF: 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.
REFERENCE   2  (bases 1 to 4824)
  AUTHORS   Dominguez-Gonzalez,C., Hernandez-Voth,A., de Fuenmayor-Fernandez de
            la Hoz,C.P., Guerrero,L.B., Moris,G., Garcia-Garcia,J., Muelas,N.,
            Leon Hernandez,J.C., Rabasa,M., Lora,D., Blazquez,A., Arenas,J. and
            Martin,M.A.
  TITLE     Metrics of progression and prognosis in untreated adults with
            thymidine kinase 2 deficiency: An observational study
  JOURNAL   Neuromuscul Disord 32 (9), 728-735 (2022)
   PUBMED   35907766
  REMARK    GeneRIF: Metrics of progression and prognosis in untreated adults
            with thymidine kinase 2 deficiency: An observational study.
REFERENCE   3  (bases 1 to 4824)
  AUTHORS   Wang,L. and Eriksson,S.
  TITLE     Mutational analyses of human thymidine kinase 2 reveal key residues
            in ATP-Mg2+ binding and catalysis
  JOURNAL   Nucleosides Nucleotides Nucleic Acids 41 (3), 264-272 (2022)
   PUBMED   34758700
  REMARK    GeneRIF: Mutational analyses of human thymidine kinase 2 reveal key
            residues in ATP-Mg(2+) binding and catalysis.
REFERENCE   4  (bases 1 to 4824)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   5  (bases 1 to 4824)
  AUTHORS   Wang,J., Kim,E., Dai,H., Stefans,V., Vogel,H., Al Jasmi,F., Schrier
            Vergano,S.A., Castro,D., Bernes,S., Bhambhani,V., Long,C.,
            El-Hattab,A.W. and Wong,L.J.
  TITLE     Clinical and molecular spectrum of thymidine kinase 2-related mtDNA
            maintenance defect
  JOURNAL   Mol Genet Metab 124 (2), 124-130 (2018)
   PUBMED   29735374
  REMARK    GeneRIF: Thymidine Kinase 2 mutation is associated with myopathic
            form of mitochondrial DNA maintenance defect.
REFERENCE   6  (bases 1 to 4824)
  AUTHORS   Kierdaszuk,B., Krawiec,K., Kazimierczuk,Z., Jacobsson,U.,
            Johansson,N.G., Munch-Petersen,B., Eriksson,S. and Shugar,D.
  TITLE     Substrate/inhibitor specificities of human deoxycytidine kinase
            (dCK) and thymidine kinases (TK1 and TK2)
  JOURNAL   Adv Exp Med Biol 431, 623-627 (1998)
   PUBMED   9598140
REFERENCE   7  (bases 1 to 4824)
  AUTHORS   Johansson,M. and Karlsson,A.
  TITLE     Cloning of the cDNA and chromosome localization of the gene for
            human thymidine kinase 2
  JOURNAL   J Biol Chem 272 (13), 8454-8458 (1997)
   PUBMED   9079672
REFERENCE   8  (bases 1 to 4824)
  AUTHORS   Wang,J., El-Hattab,A.W. and Wong,L.J.C.
  TITLE     TK2-Related Mitochondrial DNA Maintenance Defect, Myopathic Form
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   23230576
REFERENCE   9  (bases 1 to 4824)
  AUTHORS   Jansson,O., Bohman,C., Munch-Petersen,B. and Eriksson,S.
  TITLE     Mammalian thymidine kinase 2. Direct photoaffinity labeling with
            [32P]dTTP of the enzyme from spleen, liver, heart and brain
  JOURNAL   Eur J Biochem 206 (2), 485-490 (1992)
   PUBMED   1597187
REFERENCE   10 (bases 1 to 4824)
  AUTHORS   Willecke,K., Teber,T., Kucherlapati,R.S. and Ruddle,F.H.
  TITLE     Human mitochondrial thymidine kinase is coded for by a gene on
            chromosome 16 of the nucleus
  JOURNAL   Somatic Cell Genet 3 (3), 237-245 (1977)
   PUBMED   605384
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AF521891.1 and AC010542.7.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 17, 2019 this sequence version replaced NM_004614.4.
            
            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].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (1).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1660809.61244.1,
                                           SRR1660805.256015.1 [ECO:0000332]
            RNAseq introns              :: mixed/partial sample support
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000350]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000544898.6/
                                                  ENSP00000440898.2
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-23                AF521891.1         291-313
            24-24               AC010542.7         72083-72083         c
            25-796              AF521891.1         315-1086
            797-4824            AC010542.7         29987-34014         c
FEATURES             Location/Qualifiers
     source          1..4824
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="16"
                     /map="16q21"
     gene            1..4824
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /note="thymidine kinase 2"
                     /db_xref="GeneID:7084"
                     /db_xref="HGNC:HGNC:11831"
                     /db_xref="MIM:188250"
     exon            1..185
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /inference="alignment:Splign:2.1.0"
     CDS             62..859
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /EC_number="2.7.1.74"
                     /EC_number="2.7.1.21"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; mt-TK; thymidine kinase 2, mitochondrial;
                     deoxycytidine kinase TK2; 2'-deoxyuridine kinase TK2;
                     mitochondrial thymidine kinase"
                     /codon_start=1
                     /product="thymidine kinase 2, mitochondrial isoform 1
                     precursor"
                     /protein_id="NP_004605.4"
                     /db_xref="CCDS:CCDS10805.2"
                     /db_xref="GeneID:7084"
                     /db_xref="HGNC:HGNC:11831"
                     /db_xref="MIM:188250"
                     /translation="MLLWPLRGWAARALRCFGPGSRGSPASGPGPRRVQRRAWPPDKE
                     QEKEKKSVICVEGNIASGKTTCLEFFSNATDVEVLTEPVSKWRNVRGHNPLGLMYHDA
                     SRWGLTLQTYVQLTMLDRHTRPQVSSVRLMERSIHSARYIFVENLYRSGKMPEVDYVV
                     LSEWFDWILRNMDVSVDLIVYLRTNPETCYQRLKKRCREEEKVIPLEYLEAIHHLHEE
                     WLIKGSLFPMAAPVLVIEADHHMERMLELFEQNRDRILTPENRKHCP"
     exon            186..217
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /inference="alignment:Splign:2.1.0"
     exon            218..292
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /inference="alignment:Splign:2.1.0"
     exon            293..346
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /inference="alignment:Splign:2.1.0"
     exon            347..436
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /inference="alignment:Splign:2.1.0"
     exon            437..510
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /inference="alignment:Splign:2.1.0"
     exon            511..599
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /inference="alignment:Splign:2.1.0"
     exon            600..679
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /inference="alignment:Splign:2.1.0"
     exon            680..760
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /inference="alignment:Splign:2.1.0"
     exon            761..4824
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2063..2068
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /note="hexamer: AATAAA"
     polyA_site      2081
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /note="major polyA site"
     regulatory      3366..3371
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /note="hexamer: ATTATA"
     polyA_site      3385
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /note="major polyA site"
     regulatory      3422..3427
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /note="hexamer: AATATA"
     polyA_site      3445
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
     regulatory      4575..4580
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /note="hexamer: ATTAAA"
     polyA_site      4596
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
     regulatory      4805..4810
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /note="hexamer: AATAAA"
     polyA_site      4824
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
ORIGIN      
        1 agtcgtccgc gccgactcgc acaagaagga accccgggcc tctggatccg ctcgcccggc
       61 tatgctgctg tggccgctgc ggggctgggc cgcccgggcg ctgcgctgct ttgggccggg
      121 aagtcgcggg agcccggcct caggccccgg gccgcggagg gtgcagcgcc gggcctggcc
      181 tcccgataaa gaacaggaaa aagagaaaaa atcagtgatc tgtgtcgagg gcaatattgc
      241 aagtgggaag acgacatgcc tggaattctt ctccaacgcg acagacgtcg aggtgttaac
      301 ggagcctgtg tccaagtgga gaaatgtccg tggccacaat cctctgggcc tgatgtacca
      361 cgatgcctct cgctggggtc ttacgctaca gacttatgtg cagctcacca tgctggacag
      421 gcatactcgt cctcaggtgt catctgtacg gttgatggag aggtcgattc acagcgcaag
      481 atacattttt gtagaaaacc tgtatagaag tgggaagatg ccagaagtgg actatgtagt
      541 tctgtcggaa tggtttgact ggatcttgag gaacatggac gtgtctgttg atttgatagt
      601 ttaccttcgg accaatcctg agacttgtta ccagaggtta aagaagagat gcagggaaga
      661 ggagaaggtc attccgctgg aatacctgga agcaattcac catctccatg aggagtggct
      721 catcaaaggc agccttttcc ccatggcagc ccctgttctg gtgattgagg ctgaccacca
      781 catggagagg atgttagaac tctttgaaca aaatcgggat cgaatattaa ctccagagaa
      841 tcggaagcat tgcccatagg aggcaaaagg tctatggctc atgtctgaaa aatgcctgct
      901 gctgccaagt tagctattgg gagcaatctg gaaaaacttg ctcccaggag ggctttgtgt
      961 ctggccagct tgattttcct aatggtctca tctcctttgc tagtgtcttt gtcatgcgtc
     1021 tctggccctc gtgggtaaat gacaaacggg accaatgggt ttgccaagcc ctttgctgtt
     1081 cgcagcctca cattcccccg gtgcctctcc catggctttg tgctgctgag tcgctctcat
     1141 gaagccctta gggagagcac ctgttgtgtg cctgacacca cgctggagct gtgtaccaat
     1201 cgtctcagcc ttcattagga ggccgaggta ggagtcttat atcccaggtg aggaatttga
     1261 agctcagaaa ggttgagggg ctccccagag gtcacacagc ctgtgtgcag tggagctggc
     1321 accattcaga ctttcagccg actcagcaac tttcccttgc cctgggctgc ctcctcctga
     1381 gagctgttcc ccaccgccct gcctcttccg gttggaggct ctcatgtctc tttggggaga
     1441 gctggcagtg tgcggagctg ataacatttt cccaatattg agcagttccc aaggacagtc
     1501 agcatttcta gacttccaca aaattatgct gcatttggct ggagcccggt gttcagtggt
     1561 ttccctgccc gaggtcgctg cagccccatc taccacatct tcatgtggac attgagattc
     1621 acatgctggc tcctgaaggg tgctcagtct ccttggtgat taaggtcctg cttgaactgc
     1681 tgccaactcc atgtcaggga agtcgctttt ggtgcctggc tggtttgccc agagccaagc
     1741 tggggcaagg ggcagccagc cctggcttcc aaggctcccg tactgtctgt gtccttgtat
     1801 aaggagcttt gctcttggaa ttactgaaag tctgtggccc aagagagaga cacaagtggc
     1861 cttaagtctt tttgaagtgt tatttcatcc agggaaatgc ctcgagccat agagcctgaa
     1921 atcatctttg ttggctcaga aaatacctta gcttcactca gctggactgc attgaaggcg
     1981 aggctgcccc ttggatcaag cagaaaacaa gagaaagaaa gaacgttccc tttggggata
     2041 gtctggaaag ttgggatttg caaataaagg ctctggaagc attgctggtc ctgaagcttt
     2101 ggaggtgggc agagagagct tcaagaagac tagatgcaaa ccctggaaag gattaaggct
     2161 caactctgga gaaacaggcc acagcctctc agagcagctg ttggctgtaa atagaggtag
     2221 caaggccgct cccaggcccc tgtgagtgtg ggcacctgtg catgcaatgc tccgactctg
     2281 cagaggtgcc aagtgcccct gctgggccag tcccagagag ttaggaagtc aaggcctgca
     2341 actcctggtt cttcctgttt ggaccagttc ttgtgccatt ggcaggatga gaggcagcag
     2401 ccaggcggga gctgtgtcta gcagcacctg tagcccacgt gctgctaatt agctggaaaa
     2461 ctggcgaagg cagaaccttt gctaccagga atcttgacat gtggggtctg tctttgagaa
     2521 tttgtaaatg aacagtccaa tatttcctct cggctcattt tgcacatcca tttttgggga
     2581 aatgtgattt ctctctcttt tttttttttt ttttttgcct aaggcacaat ctcaagaggt
     2641 cctgagacca cgtacccatg atttttttct tgctctgtga tacccaataa ctccttcacc
     2701 taagccctgt tgttgatttt gaagtgcttc ctaggccagt gattttagct tctgccagct
     2761 gcttttgcca gtagattaac gtgtttttat ttttcaaact ccgtgtttcc taacgtggag
     2821 tgtatgggtc taagagagcc tgctgtcctc cctgccttcc accttggaga ggaggctgga
     2881 cgcatcagca gtggccaggg caggtcgcaa aatctcccag cctagagacc acacctgaaa
     2941 cggctgaagc cagcttgcac aagggctgct gtccctctgc ggcaggcaga gctggtgggg
     3001 gcaggggtca cagagcagtc atagacacca tggaccaggg caggagaagg gcagatggca
     3061 catgggcaca acagggcctt gtccttagag cactgggggg tcatggctgg gaggggcatg
     3121 gcaggggctg gcatccctgt agagccagag gggccaccca gggcagtgac attccagata
     3181 tgttgggctc acctcatcct tgctgtgaga ctggagttcc atggggacat gaagtcagta
     3241 caccgcagag ctgctcagct gctctacctc tcgctgactt ttttgttgca catatacatt
     3301 ttctttcaat tagcatttat ttcagctttt atttaagctt tttgacagta catgtaaaat
     3361 atatgattat aaccatttaa aaatacctta tgtacctggt tttttttgga aactagatag
     3421 aaatatattt atcttttaca taaaagaagt gtgtagtggg gtggtccagg gctttgtggt
     3481 ggcttagtgg ccatcggggt cccaggctct tcccaccttt ctcttttggg tccacctctt
     3541 ggctcctggc ttccttcctc tggggcctga ctgtccagga tggcagctgg agctcctgct
     3601 ctgggcacgg ttggcatcag agcccactgc tccccatcca ctctttaatc cagatgctgg
     3661 taatgtccct ttccaaggca taactaagat aagctggaag gttcttacga ggctttgcta
     3721 gaggccctgg gaggtggggg gaaaggcaag agggcagtgc ccacccatag accgggtcac
     3781 atgacctggc atcagcgccg tggggtcctt tgggcttcac ctccctctcc cctctgcccc
     3841 cacgtcatcc caccctcatc ctcaccctca ccattcccat cccgtaccgt aatgtccctt
     3901 gcaaggccta actctgtgag gaatgaaacc acctcatcct tgttccaata acatgagtga
     3961 ccgaatttac aaacgagtga atgtggacct ctggaaacat tacccagctt gtttttactt
     4021 ttcactttct ctttctgccc ctttcatttc cgtaggagcc ctttacctag atgagaagtg
     4081 tccccccgcc tggggaatat atcagtcaga acaatcttcc tgcagacatg caccattaga
     4141 cccgagtgac ggtggtgcca tttaaacctc agagcaggta aaaggtggtc ctgaaacctg
     4201 tctacccaca gggtgctatg gaatctgaat cacttctttt ttcctagagc cctggggtgg
     4261 ggagctccct caagtgttca catgtgtgtg gaatgaggaa cacccatctc cttggccctc
     4321 tccaccctga agagttagtt attaaaataa ttggcaagct cttgcaaatg tcagtcatcc
     4381 attgttcaga atggaatagc aataatacat ccctggctgc cctgggcttg gccaggatta
     4441 ctcactgaag gcctcagggt tactggcaca cactttcttt tcctaataat cccatcccct
     4501 cagctttcct aaggctagag tgaatttcgt gttcctttag tttacataag atggtgaact
     4561 tggcaaaagc tatcattaaa cagaagctaa gagaaagcct atgtcgtgga atccagaatg
     4621 ggtattgcca ttcactgctg tccacagaag ctgtcttgaa tttctttctg tgtcttttct
     4681 ttttttttct ttaagactgt tgtttaccag actgggctct gtggaacaca ggtgtcctgg
     4741 gagatggtta atcattacaa aatattggta acaatctaaa gatgcataca taagagagtg
     4801 gtcaaataaa ccattttcca ttca
//
