LOCUS       NM_016785               2715 bp    mRNA    linear   ROD 04-JUN-2024
DEFINITION  Mus musculus thiopurine methyltransferase (Tpmt), mRNA.
ACCESSION   NM_016785
VERSION     NM_016785.2
KEYWORDS    RefSeq; RefSeq Select.
SOURCE      Mus musculus (house mouse)
  ORGANISM  Mus musculus
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
            Muroidea; Muridae; Murinae; Mus; Mus.
REFERENCE   1  (bases 1 to 2715)
  AUTHORS   Pristup,J., Schaeffeler,E., Arjune,S., Hofmann,U., Angel
            Santamaria-Araujo,J., Leuthold,P., Friedrich,N., Nauck,M., Mayr,S.,
            Haag,M., Muerdter,T., Marner,F.J., Relling,M.V., Evans,W.E.,
            Schwarz,G. and Schwab,M.
  TITLE     Molybdenum Cofactor Catabolism Unravels the Physiological Role of
            the Drug Metabolizing Enzyme Thiopurine S-Methyltransferase
  JOURNAL   Clin Pharmacol Ther 112 (4), 808-816 (2022)
   PUBMED   35538648
  REMARK    GeneRIF: Molybdenum Cofactor Catabolism Unravels the Physiological
            Role of the Drug Metabolizing Enzyme Thiopurine
            S-Methyltransferase.
REFERENCE   2  (bases 1 to 2715)
  AUTHORS   Bhavsar,A.P., Gunaretnam,E.P., Li,Y., Hasbullah,J.S., Carleton,B.C.
            and Ross,C.J.
  TITLE     Pharmacogenetic variants in TPMT alter cellular responses to
            cisplatin in inner ear cell lines
  JOURNAL   PLoS One 12 (4), e0175711 (2017)
   PUBMED   28406961
  REMARK    GeneRIF: With the significant mitigation of TPMT wild
            type-expressing cells to cisplatin cytotoxicity, findings
            demonstrate a drug-gene interaction between increased TPMT activity
            and decreased susceptibility to cisplatin-induced toxicity of inner
            ear cells.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 2715)
  AUTHORS   Ramsey,L.B., Janke,L.J., Edick,M.J., Cheng,C., Williams,R.T.,
            Sherr,C.J., Evans,W.E. and Relling,M.V.
  TITLE     Host thiopurine methyltransferase status affects mercaptopurine
            antileukemic effectiveness in a murine model
  JOURNAL   Pharmacogenet Genomics 24 (5), 263-271 (2014)
   PUBMED   24710003
  REMARK    GeneRIF: These findings support the notion that germline
            polymorphisms in Tpmt affect not only host tissue toxicity but also
            antitumor effectiveness.
REFERENCE   4  (bases 1 to 2715)
  AUTHORS   Hartford,C., Vasquez,E., Schwab,M., Edick,M.J., Rehg,J.E.,
            Grosveld,G., Pui,C.H., Evans,W.E. and Relling,M.V.
  TITLE     Differential effects of targeted disruption of thiopurine
            methyltransferase on mercaptopurine and thioguanine
            pharmacodynamics
  JOURNAL   Cancer Res 67 (10), 4965-4972 (2007)
   PUBMED   17510427
REFERENCE   5  (bases 1 to 2715)
  AUTHORS   Watters,J.W., Zhang,W., Meucci,M.A., Hou,W., Ma,M.K. and
            McLeod,H.L.
  TITLE     Analysis of variation in mouse TPMT genotype, expression and
            activity
  JOURNAL   Pharmacogenetics 14 (4), 247-254 (2004)
   PUBMED   15083069
  REMARK    GeneRIF: suggestion that differential mouse TPMT activity is due to
            variation in mRNA expression
REFERENCE   6  (bases 1 to 2715)
  AUTHORS   Fessing,M.Y., Belkov,V.M., Krynetski,E.Y. and Evans,W.E.
  TITLE     Molecular cloning and functional characterization of the cDNA
            encoding the murine thiopurine S-methyltransferase (TPMT)
  JOURNAL   FEBS Lett 424 (3), 143-145 (1998)
   PUBMED   9539138
REFERENCE   7  (bases 1 to 2715)
  AUTHORS   Otterness,D.M. and Weinshilboum,R.M.
  TITLE     Mouse thiopurine methyltransferase pharmacogenetics: biochemical
            studies and recombinant inbred strains
  JOURNAL   J Pharmacol Exp Ther 243 (1), 180-186 (1987)
   PUBMED   3668849
REFERENCE   8  (bases 1 to 2715)
  AUTHORS   Otterness,D.M. and Weinshilboum,R.M.
  TITLE     Mouse thiopurine methyltransferase pharmacogenetics: monogenic
            inheritance
  JOURNAL   J Pharmacol Exp Ther 240 (3), 817-824 (1987)
   PUBMED   3559976
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            AC096628.14, CF106558.1 and AF037044.1.
            
            On Jul 14, 2009 this sequence version replaced NM_016785.1.
            
            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.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AF046887.1, AF037043.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMN01164135 [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-114               AC096628.14        116719-116832       c
            115-140             CF106558.1         37-62
            141-1023            AF037044.1         1-883
            1024-2715           AC096628.14        97158-98849         c
FEATURES             Location/Qualifiers
     source          1..2715
                     /organism="Mus musculus"
                     /mol_type="mRNA"
                     /strain="C57BL/6"
                     /db_xref="taxon:10090"
                     /chromosome="13"
                     /map="13 24.5 cM"
     gene            1..2715
                     /gene="Tpmt"
                     /note="thiopurine methyltransferase"
                     /db_xref="GeneID:22017"
                     /db_xref="MGI:MGI:98812"
     exon            1..114
                     /gene="Tpmt"
                     /inference="alignment:Splign:2.1.0"
     exon            115..295
                     /gene="Tpmt"
                     /inference="alignment:Splign:2.1.0"
     CDS             171..893
                     /gene="Tpmt"
                     /EC_number="2.1.1.67"
                     /codon_start=1
                     /product="thiopurine S-methyltransferase"
                     /protein_id="NP_058065.2"
                     /db_xref="CCDS:CCDS26488.1"
                     /db_xref="GeneID:22017"
                     /db_xref="MGI:MGI:98812"
                     /translation="MSLDMKEHPDAEVQKNQVLTLEDWKEKWVTRHISFHQEQGHQLL
                     KKHLDTFLKGQSGLRVFFPLCGKAVEMKWFADRGHTVVGVEISEIGIREFFAEQNLSY
                     TEEPLAEIAGAKVFKSSSGSISLYCCSIFDLPRANIGKFDRIWDRGALVAINPGDHDR
                     YADIILSLLRKEFQYLVAVLSYDPTKHAGPPFYVPSAELKRLFGTKCSMQCLEEVDAL
                     EERHKAWGLDYLFEKLYLLTEK"
     exon            296..388
                     /gene="Tpmt"
                     /inference="alignment:Splign:2.1.0"
     exon            389..521
                     /gene="Tpmt"
                     /inference="alignment:Splign:2.1.0"
     exon            522..574
                     /gene="Tpmt"
                     /inference="alignment:Splign:2.1.0"
     exon            575..649
                     /gene="Tpmt"
                     /inference="alignment:Splign:2.1.0"
     exon            650..735
                     /gene="Tpmt"
                     /inference="alignment:Splign:2.1.0"
     exon            736..780
                     /gene="Tpmt"
                     /inference="alignment:Splign:2.1.0"
     exon            781..2715
                     /gene="Tpmt"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1058..1063
                     /regulatory_class="polyA_signal_sequence"
                     /gene="Tpmt"
                     /note="hexamer: ATTAAA"
     polyA_site      1081
                     /gene="Tpmt"
                     /note="major polyA site"
     regulatory      2695..2700
                     /regulatory_class="polyA_signal_sequence"
                     /gene="Tpmt"
                     /note="hexamer: AATAAA"
     polyA_site      2713
                     /gene="Tpmt"
ORIGIN      
        1 gaccacattg ggcggggcct tcgcccctgg ggcggggcct gtgagtcctt gcacagctcc
       61 cggcttacaa aggcgggcta gtgtctgaga ggtaagcagc tagctgcagc caaggcactg
      121 gagacaccaa cctcagagac aaaaattgtc tacaacccgt ggatggtacc atgtcccttg
      181 atatgaaaga gcaccctgat gctgaggtac aaaagaacca agtactaacc ctggaagact
      241 ggaaagagaa gtgggtgacc cgtcacatct cattccatca ggagcaaggg catcagctgt
      301 tgaagaagca tttggataca tttcttaaag gccagagtgg actgcgagtg tttttccccc
      361 tctgtggaaa agccgttgag atgaaatggt tcgcagatcg gggccacact gtagttggtg
      421 tggaaatcag tgaaattggg attcgggaat tttttgcaga acagaatctt tcctacacag
      481 aagaaccgct cgccgaaatt gctggagcca aagtatttaa gagttcttca gggagcattt
      541 ccttatactg ctgcagcata tttgatcttc ctagagcaaa cattggcaag tttgacagga
      601 tttgggatag aggagcatta gtggctatca atccaggcga tcatgatcgc tatgcagata
      661 taatactgtc cctactgaga aaagagtttc agtaccttgt ggctgtcctt tcttatgatc
      721 caacaaaaca cgcaggccca ccattttatg ttccatctgc tgaacttaaa aggttatttg
      781 gtacaaaatg cagcatgcaa tgccttgaag aggtagatgc tttggaagaa aggcataaag
      841 cctggggtct tgactacctt tttgaaaaat tgtatctcct tacagagaag taaaaaacca
      901 gcctggtagt ggagcacacc ttttatctca gcaggctagc ctggtctacc agtgagttcc
      961 aagacagcca gagagaccct atctggaaaa accaaataga aaaccaacca aacaaacaaa
     1021 aaacacccaa tcaatccctg tatgagtttt ttgaacaatt aaaaattatg ttgagggtta
     1081 atgtattagc catggtttct gttcctgcac aaaacatcat aatcaagaag aaagttgtca
     1141 cacagcagct tcacaccaga gtcttctaga atgttctctg aaacgtttag gcaactcagg
     1201 ttctgattgt tcctgaggat gtcagccagg tcctagcagc ctccagtgat gagacaggct
     1261 ctcaccctta gtgacacaag tgcactgtct gagccataca ctcgccggct gcttctccat
     1321 gtccttgtca tgcagctccg actcctgttt ggtgacatcc catcccatcc cctctaagct
     1381 gtcagtgcta aatagttttg caggttggga tgggatctcc tctgtgggag ctgagggact
     1441 gggctgctct ctggagatca gcccagctag gcttgctgtc ttcagttgct tcacatcttg
     1501 agagcagaag tagaagatgt gggagaattt gctctgaaac gccaggcctt ctgaccagac
     1561 aggcgttcaa tttttcaaca taatagtctt gccgattcca gcccacgtgt ggcttctttt
     1621 cagttccctt tggtacaaga aggttctcaa gatgattata ttcatcctcg aaaaaattct
     1681 gaaggctgtt atggaacttt ctggaaaaat catgggtcag cttctttaaa tgagcttgat
     1741 atatcattgg gtatggagca atctctcctg ttgccctctc tctctctttt aattttttaa
     1801 aaagtatatg agtacacact gtaactgtac agatagttgt gagccttcat ctggttgttg
     1861 ggaattgact ttaggacctc tgctcactcc agtcagcctc cttgctcagg cccaaagatt
     1921 tattattata aataagtact ctataatctg tcttcagaca gcaccagaag agggcatcag
     1981 atctcgttac aggtggttgt gagccaccat gtggttgctg ggatttgaac tcaggacctt
     2041 cagaagagca gtgagtgctc ttacttgctg agccatctct ccagtcccca gttgccctct
     2101 cagtaagatc cttcccattg gtcttctgaa ggatgagggt cttataaccc acacccacag
     2161 tgacacacct actccgacaa ggccacacct tctaatagtg ccactccctt ggctgagcat
     2221 atacaaacca tcacagttaa aaatacaatc acttaatttt tcttctcatg caacattcag
     2281 atctttgctc actacttttt aaaaatgaaa tcacacacta aaatgttata agtcaatcaa
     2341 tcctttaaag attgtatgac tggtagcaga acattaaata ctcgtgtgtc ttttttatag
     2401 tcagcgtgta tttcttctat aactaaaaaa aaaacaaaaa aataatgctt ttaactttaa
     2461 acaacaacac gttctgtatg gaaatataac attttaacag gatttgggat agtctaaatt
     2521 ttgtattaaa aattatactt tgctatagat cttaatctac ttaggacccg gaactacatc
     2581 ttcaccggct tctccacttg tataattcta tatgtaacag agtcaagaaa tgtaaaaaaa
     2641 aaaaaaatta aatcaaccta tatggaaagg tatttttttc ctcacaactg taagaataaa
     2701 accttttaaa atatt
//
