LOCUS       NM_001271934            4919 bp    mRNA    linear   PRI 10-OCT-2024
DEFINITION  Homo sapiens thymidine kinase 2 (TK2), transcript variant 5, mRNA.
ACCESSION   NM_001271934
VERSION     NM_001271934.2
KEYWORDS    RefSeq.
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 4919)
  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 4919)
  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 4919)
  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 4919)
  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 4919)
  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 4919)
  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 4919)
  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 4919)
  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 4919)
  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 4919)
  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, AK303590.1,
            BC142970.1, AC010542.7 and AL038860.1.
            
            On May 31, 2019 this sequence version replaced NM_001271934.1.
            
            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 (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.
            
            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 :: BC142970.1 [ECO:0000332]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-23                AF521891.1         291-313
            24-217              AK303590.1         92-285
            218-712             BC142970.1         309-803
            713-858             AK303590.1         632-777
            859-1301            BC142970.1         950-1392
            1302-4830           AC010542.7         30076-33604         c
            4831-4919           AL038860.1         20-108              c
FEATURES             Location/Qualifiers
     source          1..4919
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="16"
                     /map="16q21"
     gene            1..4919
                     /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"
     exon            186..217
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /inference="alignment:Splign:2.1.0"
     exon            218..312
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /inference="alignment:Splign:2.1.0"
     CDS             304..954
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /EC_number="2.7.1.74"
                     /EC_number="2.7.1.21"
                     /note="isoform 5 is encoded by transcript variant 5;
                     mt-TK; thymidine kinase 2, mitochondrial; deoxycytidine
                     kinase TK2; 2'-deoxyuridine kinase TK2; mitochondrial
                     thymidine kinase"
                     /codon_start=1
                     /product="thymidine kinase 2 isoform 5"
                     /protein_id="NP_001258863.1"
                     /db_xref="GeneID:7084"
                     /db_xref="HGNC:HGNC:11831"
                     /db_xref="MIM:188250"
                     /translation="MTSICVEGNIASGKTTCLEFFSNATDVEVLTEPVSKWRNVRGHN
                     PLGLMYHDASRWGLTLQTYVQLTMLDRHTRPQVSSVRLMERSIHSARYIFVENLYRSG
                     KMPEVDYVVLSEWFDWILRNMDVSVDLIVYLRTNPETCYQRLKKRCREEEKVIPLEYL
                     EAIHHLHEEWLIKGSLFPMAAPVLVIEADHHMERMLELFEQNRDRILTPENRKHCP"
     exon            313..387
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /inference="alignment:Splign:2.1.0"
     exon            388..441
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /inference="alignment:Splign:2.1.0"
     exon            442..531
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /inference="alignment:Splign:2.1.0"
     exon            532..605
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /inference="alignment:Splign:2.1.0"
     exon            606..694
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /inference="alignment:Splign:2.1.0"
     exon            695..774
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /inference="alignment:Splign:2.1.0"
     exon            775..855
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /inference="alignment:Splign:2.1.0"
     exon            856..4919
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2158..2163
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /note="hexamer: AATAAA"
     polyA_site      2176
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /note="major polyA site"
     regulatory      3461..3466
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /note="hexamer: ATTATA"
     polyA_site      3480
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /note="major polyA site"
     regulatory      3517..3522
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /note="hexamer: AATATA"
     polyA_site      3540
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
     regulatory      4670..4675
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /note="hexamer: ATTAAA"
     polyA_site      4691
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
     regulatory      4900..4905
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TK2"
                     /gene_synonym="MTDPS2; MTTK; PEOB3; SCA31; TK2-EXT"
                     /note="hexamer: AATAAA"
     polyA_site      4919
                     /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 atcagtgaga cggcgtcttg ctgtgttgcc
      241 caggctggcc tccaactcct gggctcaagt gatcctctgg catcagcctc ctgagtagct
      301 gtgatgacaa gtatctgtgt cgagggcaat attgcaagtg ggaagacgac atgcctggaa
      361 ttcttctcca acgcgacaga cgtcgaggtg ttaacggagc ctgtgtccaa gtggagaaat
      421 gtccgtggcc acaatcctct gggcctgatg taccacgatg cctctcgctg gggtcttacg
      481 ctacagactt atgtgcagct caccatgctg gacaggcata ctcgtcctca ggtgtcatct
      541 gtacggttga tggagaggtc gattcacagc gcaagataca tttttgtaga aaacctgtat
      601 agaagtggga agatgccaga agtggactat gtagttctgt cggaatggtt tgactggatc
      661 ttgaggaaca tggacgtgtc tgttgatttg atagtttacc ttcggaccaa tcctgagact
      721 tgttaccaga ggttaaagaa gagatgcagg gaagaggaga aggtcattcc gctggaatac
      781 ctggaagcaa ttcaccatct ccatgaggag tggctcatca aaggcagcct tttccccatg
      841 gcagcccctg ttctggtgat tgaggctgac caccacatgg agaggatgtt agaactcttt
      901 gaacaaaatc gggatcgaat attaactcca gagaatcgga agcattgccc ataggaggca
      961 aaaggtctat ggctcatgtc tgaaaaatgc ctgctgctgc caagttagct attgggagca
     1021 atctggaaaa acttgctccc aggagggctt tgtgtctggc cagcttgatt ttcctaatgg
     1081 tctcatctcc tttgctagtg tctttgtcat gcgtctctgg ccctcgtggg taaatgacaa
     1141 acgggaccaa tgggtttgcc aagccctttg ctgttcgcag cctcacattc ccccggtgcc
     1201 tctcccatgg ctttgtgctg ctgagtcgct ctcatgaagc ccttagggag agcacctgtt
     1261 gtgtgcctga caccacgctg gagctgtgta ccaatcgtct cagccttcat taggaggccg
     1321 aggtaggagt cttatatccc aggtgaggaa tttgaagctc agaaaggttg aggggctccc
     1381 cagaggtcac acagcctgtg tgcagtggag ctggcaccat tcagactttc agccgactca
     1441 gcaactttcc cttgccctgg gctgcctcct cctgagagct gttccccacc gccctgcctc
     1501 ttccggttgg aggctctcat gtctctttgg ggagagctgg cagtgtgcgg agctgataac
     1561 attttcccaa tattgagcag ttcccaagga cagtcagcat ttctagactt ccacaaaatt
     1621 atgctgcatt tggctggagc ccggtgttca gtggtttccc tgcccgaggt cgctgcagcc
     1681 ccatctacca catcttcatg tggacattga gattcacatg ctggctcctg aagggtgctc
     1741 agtctccttg gtgattaagg tcctgcttga actgctgcca actccatgtc agggaagtcg
     1801 cttttggtgc ctggctggtt tgcccagagc caagctgggg caaggggcag ccagccctgg
     1861 cttccaaggc tcccgtactg tctgtgtcct tgtataagga gctttgctct tggaattact
     1921 gaaagtctgt ggcccaagag agagacacaa gtggccttaa gtctttttga agtgttattt
     1981 catccaggga aatgcctcga gccatagagc ctgaaatcat ctttgttggc tcagaaaata
     2041 ccttagcttc actcagctgg actgcattga aggcgaggct gccccttgga tcaagcagaa
     2101 aacaagagaa agaaagaacg ttccctttgg ggatagtctg gaaagttggg atttgcaaat
     2161 aaaggctctg gaagcattgc tggtcctgaa gctttggagg tgggcagaga gagcttcaag
     2221 aagactagat gcaaaccctg gaaaggatta aggctcaact ctggagaaac aggccacagc
     2281 ctctcagagc agctgttggc tgtaaataga ggtagcaagg ccgctcccag gcccctgtga
     2341 gtgtgggcac ctgtgcatgc aatgctccga ctctgcagag gtgccaagtg cccctgctgg
     2401 gccagtccca gagagttagg aagtcaaggc ctgcaactcc tggttcttcc tgtttggacc
     2461 agttcttgtg ccattggcag gatgagaggc agcagccagg cgggagctgt gtctagcagc
     2521 acctgtagcc cacgtgctgc taattagctg gaaaactggc gaaggcagaa cctttgctac
     2581 caggaatctt gacatgtggg gtctgtcttt gagaatttgt aaatgaacag tccaatattt
     2641 cctctcggct cattttgcac atccattttt ggggaaatgt gatttctctc tctttttttt
     2701 tttttttttt tgcctaaggc acaatctcaa gaggtcctga gaccacgtac ccatgatttt
     2761 tttcttgctc tgtgataccc aataactcct tcacctaagc cctgttgttg attttgaagt
     2821 gcttcctagg ccagtgattt tagcttctgc cagctgcttt tgccagtaga ttaacgtgtt
     2881 tttatttttc aaactccgtg tttcctaacg tggagtgtat gggtctaaga gagcctgctg
     2941 tcctccctgc cttccacctt ggagaggagg ctggacgcat cagcagtggc cagggcaggt
     3001 cgcaaaatct cccagcctag agaccacacc tgaaacggct gaagccagct tgcacaaggg
     3061 ctgctgtccc tctgcggcag gcagagctgg tgggggcagg ggtcacagag cagtcataga
     3121 caccatggac cagggcagga gaagggcaga tggcacatgg gcacaacagg gccttgtcct
     3181 tagagcactg gggggtcatg gctgggaggg gcatggcagg ggctggcatc cctgtagagc
     3241 cagaggggcc acccagggca gtgacattcc agatatgttg ggctcacctc atccttgctg
     3301 tgagactgga gttccatggg gacatgaagt cagtacaccg cagagctgct cagctgctct
     3361 acctctcgct gacttttttg ttgcacatat acattttctt tcaattagca tttatttcag
     3421 cttttattta agctttttga cagtacatgt aaaatatatg attataacca tttaaaaata
     3481 ccttatgtac ctggtttttt ttggaaacta gatagaaata tatttatctt ttacataaaa
     3541 gaagtgtgta gtggggtggt ccagggcttt gtggtggctt agtggccatc ggggtcccag
     3601 gctcttccca cctttctctt ttgggtccac ctcttggctc ctggcttcct tcctctgggg
     3661 cctgactgtc caggatggca gctggagctc ctgctctggg cacggttggc atcagagccc
     3721 actgctcccc atccactctt taatccagat gctggtaatg tccctttcca aggcataact
     3781 aagataagct ggaaggttct tacgaggctt tgctagaggc cctgggaggt ggggggaaag
     3841 gcaagagggc agtgcccacc catagaccgg gtcacatgac ctggcatcag cgccgtgggg
     3901 tcctttgggc ttcacctccc tctcccctct gcccccacgt catcccaccc tcatcctcac
     3961 cctcaccatt cccatcccgt accgtaatgt cccttgcaag gcctaactct gtgaggaatg
     4021 aaaccacctc atccttgttc caataacatg agtgaccgaa tttacaaacg agtgaatgtg
     4081 gacctctgga aacattaccc agcttgtttt tacttttcac tttctctttc tgcccctttc
     4141 atttccgtag gagcccttta cctagatgag aagtgtcccc ccgcctgggg aatatatcag
     4201 tcagaacaat cttcctgcag acatgcacca ttagacccga gtgacggtgg tgccatttaa
     4261 acctcagagc aggtaaaagg tggtcctgaa acctgtctac ccacagggtg ctatggaatc
     4321 tgaatcactt cttttttcct agagccctgg ggtggggagc tccctcaagt gttcacatgt
     4381 gtgtggaatg aggaacaccc atctccttgg ccctctccac cctgaagagt tagttattaa
     4441 aataattggc aagctcttgc aaatgtcagt catccattgt tcagaatgga atagcaataa
     4501 tacatccctg gctgccctgg gcttggccag gattactcac tgaaggcctc agggttactg
     4561 gcacacactt tcttttccta ataatcccat cccctcagct ttcctaaggc tagagtgaat
     4621 ttcgtgttcc tttagtttac ataagatggt gaacttggca aaagctatca ttaaacagaa
     4681 gctaagagaa agcctatgtc gtggaatcca gaatgggtat tgccattcac tgctgtccac
     4741 agaagctgtc ttgaatttct ttctgtgtct tttctttttt tttctttaag actgttgttt
     4801 accagactgg gctctgtgga acacaggtgt cctgggagat ggttaatcat tacaaaatat
     4861 tggtaacaat ctaaagatgc atacataaga gagtggtcaa ataaaccatt ttccattca
//
