LOCUS       NM_001025248            2141 bp    mRNA    linear   PRI 07-FEB-2025
DEFINITION  Homo sapiens deoxyuridine triphosphatase (DUT), transcript variant
            1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_001025248
VERSION     NM_001025248.2
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 2141)
  AUTHORS   Sarre,R., Dobrovolska,O., Lundstrom,P., Turcu,D., Agback,T.,
            Halskau,O. and Isaksson,J.
  TITLE     Structural dynamics of human deoxyuridine 5'-triphosphate
            nucleotidohydrolase (dUTPase)
  JOURNAL   Sci Rep 14 (1), 26081 (2024)
   PUBMED   39477983
  REMARK    GeneRIF: Structural dynamics of human deoxyuridine 5'-triphosphate
            nucleotidohydrolase (dUTPase).
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 2141)
  AUTHORS   Racz,G.A., Nagy,N., Varady,G., Tovari,J., Apati,A. and
            Vertessy,B.G.
  TITLE     Discovery of two new isoforms of the human DUT gene
  JOURNAL   Sci Rep 13 (1), 7760 (2023)
   PUBMED   37173337
  REMARK    GeneRIF: Discovery of two new isoforms of the human DUT gene.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 2141)
  AUTHORS   Wang,Y., Gao,S., Chen,L., Liu,S., Ma,J., Cao,Z. and Li,Q.
  TITLE     DUT enhances drug resistance to proteasome inhibitors via promoting
            mitochondrial function in multiple myeloma
  JOURNAL   Carcinogenesis 43 (11), 1030-1038 (2022)
   PUBMED   36426924
  REMARK    GeneRIF: DUT enhances drug resistance to proteasome inhibitors via
            promoting mitochondrial function in multiple myeloma.
REFERENCE   4  (bases 1 to 2141)
  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 2141)
  AUTHORS   Szabo,J.E., Nyiri,K., Andrasi,D., Matejka,J., Ozohanics,O. and
            Vertessy,B.
  TITLE     Redox status of cysteines does not alter functional properties of
            human dUTPase but the Y54C mutation involved in monogenic diabetes
            decreases protein stability
  JOURNAL   Sci Rep 11 (1), 19197 (2021)
   PUBMED   34584184
  REMARK    GeneRIF: Redox status of cysteines does not alter functional
            properties of human dUTPase but the Y54C mutation involved in
            monogenic diabetes decreases protein stability.
            Erratum:[Sci Rep. 2021 Oct 29;11(1):21666. doi:
            10.1038/s41598-021-01241-2.. PMID: 34716399]
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 2141)
  AUTHORS   Ladner,R.D., Carr,S.A., Huddleston,M.J., McNulty,D.E. and
            Caradonna,S.J.
  TITLE     Identification of a consensus cyclin-dependent kinase
            phosphorylation site unique to the nuclear form of human
            deoxyuridine triphosphate nucleotidohydrolase
  JOURNAL   J Biol Chem 271 (13), 7752-7757 (1996)
   PUBMED   8631817
REFERENCE   7  (bases 1 to 2141)
  AUTHORS   Ladner,R.D., McNulty,D.E., Carr,S.A., Roberts,G.D. and
            Caradonna,S.J.
  TITLE     Characterization of distinct nuclear and mitochondrial forms of
            human deoxyuridine triphosphate nucleotidohydrolase
  JOURNAL   J Biol Chem 271 (13), 7745-7751 (1996)
   PUBMED   8631816
REFERENCE   8  (bases 1 to 2141)
  AUTHORS   Strahler,J.R., Zhu,X.X., Hora,N., Wang,Y.K., Andrews,P.C.,
            Roseman,N.A., Neel,J.V., Turka,L. and Hanash,S.M.
  TITLE     Maturation stage and proliferation-dependent expression of dUTPase
            in human T cells
  JOURNAL   Proc Natl Acad Sci U S A 90 (11), 4991-4995 (1993)
   PUBMED   8389461
REFERENCE   9  (bases 1 to 2141)
  AUTHORS   McIntosh,E.M., Ager,D.D., Gadsden,M.H. and Haynes,R.H.
  TITLE     Human dUTP pyrophosphatase: cDNA sequence and potential biological
            importance of the enzyme
  JOURNAL   Proc Natl Acad Sci U S A 89 (17), 8020-8024 (1992)
   PUBMED   1325640
  REMARK    Erratum:[Proc Natl Acad Sci U S A 1993 May 1;90(9):4328]
REFERENCE   10 (bases 1 to 2141)
  AUTHORS   Babicev,S.I. and Briskin,B.S.
  TITLE     [Method for plastic surgery of the small intestine after the
            resection of the esophagus and proximal portion of the stomach for
            cancer]
  JOURNAL   Rozhl Chir 54 (1), 11-16 (1975)
   PUBMED   1091006
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BF697257.1, BC070339.1,
            AC023355.5 and BI257870.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_001025248.1.
            
            Summary: This gene encodes an essential enzyme of nucleotide
            metabolism. The encoded protein forms a ubiquitous, homotetrameric
            enzyme that hydrolyzes dUTP to dUMP and pyrophosphate. This
            reaction serves two cellular purposes: providing a precursor (dUMP)
            for the synthesis of thymine nucleotides needed for DNA
            replication, and limiting intracellular pools of dUTP. Elevated
            levels of dUTP lead to increased incorporation of uracil into DNA,
            which induces extensive excision repair mediated by uracil
            glycosylase. This repair process, resulting in the removal and
            reincorporation of dUTP, is self-defeating and leads to DNA
            fragmentation and cell death. Alternative splicing of this gene
            leads to different isoforms that localize to either the
            mitochondrion or nucleus. A related pseudogene is located on
            chromosome 19. [provided by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (1), also known as DUT-M,
            represents the longest transcript. It encodes the longest isoform
            (1), which includes a mitochondrial targeting sequence.
            
            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 :: SRR1660809.76151.1,
                                           SRR3476690.1142506.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1966682, SAMEA1968189
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000331200.8/
                                                  ENSP00000370376.2
            RefSeq Select criteria             :: based on conservation,
                                                  longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-11                BF697257.1         10-20
            12-905              BC070339.1         1-894
            906-1188            BC070339.1         896-1178
            1189-2081           AC023355.5         125580-126472
            2082-2141           BI257870.1         101-160
FEATURES             Location/Qualifiers
     source          1..2141
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="15"
                     /map="15q21.1"
     gene            1..2141
                     /gene="DUT"
                     /gene_synonym="BMFDMS; dUTPase"
                     /note="deoxyuridine triphosphatase"
                     /db_xref="GeneID:1854"
                     /db_xref="HGNC:HGNC:3078"
                     /db_xref="MIM:601266"
     exon            1..367
                     /gene="DUT"
                     /gene_synonym="BMFDMS; dUTPase"
                     /inference="alignment:Splign:2.1.0"
     CDS             88..846
                     /gene="DUT"
                     /gene_synonym="BMFDMS; dUTPase"
                     /EC_number="3.6.1.23"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; dUTP pyrophosphatase; dUTP nucleotidohydrolase;
                     deoxyuridine 5'-triphosphate nucleotidohydrolase,
                     mitochondrial; dUTP diphosphatase"
                     /codon_start=1
                     /product="deoxyuridine 5'-triphosphate
                     nucleotidohydrolase, mitochondrial isoform 1 precursor"
                     /protein_id="NP_001020419.1"
                     /db_xref="CCDS:CCDS32231.1"
                     /db_xref="GeneID:1854"
                     /db_xref="HGNC:HGNC:3078"
                     /db_xref="MIM:601266"
                     /translation="MTPLCPRPALCYHFLTSLLRSAMQNARGARQRAEAAVLSGPGPP
                     LGRAAQHGIPRPLSSAGRLSQGCRGASTVGAAGWKGELPKAGGSPAPGPETPAISPSK
                     RARPAEVGGMQLRFARLSEHATAPTRGSARAAGYDLYSAYDYTIPPMEKAVVKTDIQI
                     ALPSGCYGRVAPRSGLAAKHFIDVGAGVIDEDYRGNVGVVLFNFGKEKFEVKKGDRIA
                     QLICERIFYPEIEEVQALDDTERGSGGFGSTGKN"
     exon            368..506
                     /gene="DUT"
                     /gene_synonym="BMFDMS; dUTPase"
                     /inference="alignment:Splign:2.1.0"
     exon            507..598
                     /gene="DUT"
                     /gene_synonym="BMFDMS; dUTPase"
                     /inference="alignment:Splign:2.1.0"
     exon            599..643
                     /gene="DUT"
                     /gene_synonym="BMFDMS; dUTPase"
                     /inference="alignment:Splign:2.1.0"
     exon            644..718
                     /gene="DUT"
                     /gene_synonym="BMFDMS; dUTPase"
                     /inference="alignment:Splign:2.1.0"
     exon            719..789
                     /gene="DUT"
                     /gene_synonym="BMFDMS; dUTPase"
                     /inference="alignment:Splign:2.1.0"
     exon            790..2141
                     /gene="DUT"
                     /gene_synonym="BMFDMS; dUTPase"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1160..1165
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DUT"
                     /gene_synonym="BMFDMS; dUTPase"
                     /note="hexamer: ATTAAA"
     polyA_site      1188
                     /gene="DUT"
                     /gene_synonym="BMFDMS; dUTPase"
                     /note="major polyA site"
     regulatory      1305..1310
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DUT"
                     /gene_synonym="BMFDMS; dUTPase"
                     /note="hexamer: AATAAA"
     regulatory      1311..1316
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DUT"
                     /gene_synonym="BMFDMS; dUTPase"
                     /note="hexamer: AATGAA"
     polyA_site      1323
                     /gene="DUT"
                     /gene_synonym="BMFDMS; dUTPase"
     polyA_site      1334
                     /gene="DUT"
                     /gene_synonym="BMFDMS; dUTPase"
     regulatory      2110..2115
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DUT"
                     /gene_synonym="BMFDMS; dUTPase"
                     /note="hexamer: AATAAA"
     polyA_site      2141
                     /gene="DUT"
                     /gene_synonym="BMFDMS; dUTPase"
ORIGIN      
        1 gttcccagga cgggcgcgtc ttcagggtgg aagcctggcg cacgtccgga ggtgccgagg
       61 acccaaccag cccaaactct gggggaaatg actcccctct gccctcgccc cgcgctctgc
      121 taccatttcc ttacgtctct gcttcgctca gcgatgcaaa acgcgcgagg cgcacggcag
      181 agggccgaag ccgcggtact ctccgggcca ggcccgcccc tcggccgcgc cgcgcagcac
      241 gggattcccc ggccgctgtc cagcgctggc cgcctgagcc aaggctgccg cggagccagt
      301 acagtcgggg ccgctggctg gaagggcgag cttcctaagg cggggggaag cccggcgccg
      361 gggccggaga cacccgccat ttcacccagt aagcgggccc ggcctgcgga ggtgggcggc
      421 atgcagctcc gctttgcccg gctctccgag cacgccacgg cccccacccg gggctccgcg
      481 cgcgccgcgg gctacgacct gtacagtgcc tatgattaca caataccacc tatggagaaa
      541 gctgttgtga aaacggacat tcagatagcg ctcccttctg ggtgttatgg aagagtggct
      601 ccacggtcag gcttggctgc aaaacacttt attgatgtag gagctggtgt catagatgaa
      661 gattatagag gaaatgttgg tgttgtactg tttaattttg gcaaagaaaa gtttgaagtc
      721 aaaaaaggtg atcgaattgc acagctcatt tgcgaacgga ttttttatcc agaaatagaa
      781 gaagttcaag ccttggatga caccgaaagg ggttcaggag gttttggttc cactggaaag
      841 aattaaaatt tatgccaaga acagaaaaca agaagtcata cctttttctt aaaaaaaaaa
      901 aaaaagtttt tgcttcaagt gttttggtgt tttgcacttc tgtaaactta ctagctttac
      961 cttctaaaag tactgcattt tttacttttt tttatgatca aggaaaagat cattaaaaaa
     1021 aaacacaaag aagtttttct ttgtgtttgg atcaaaaaga aactttgttt ttccgcaatt
     1081 gaaggttgta tgtaaatctg ctttgtggtg acctgatgta aacagtgtct tcttaaaatc
     1141 aaatgtaaat caattacaga ttaaaaaaaa aagcctgtat ttaactcata tgatctccct
     1201 tcagcaactt attttgcttt aattgcttta aatcttaagc aatatttttt attcagtaaa
     1261 caaattcttt cacaaggtac aaaatcttgc ataagctgaa ctaaaataaa aatgaaaagg
     1321 agagattaaa ggtattcctt gttcttccct tctcttcact agtctaaaaa cttcttttta
     1381 atcttaagat tctttgtgat gagggtgaga aaaagaatcc tcagtttatt tttccactat
     1441 taatctttct tttgataaat cctctattga ctgggtagag gtatgtttgt gaaagacatg
     1501 taacttgggg atttgttact ttaggtttgt tcccttgaat ttcatctcat caggcaaatt
     1561 gtactagttg tagttacgag ttttccctca gtgaagtagc aataggctgt aatcaagaaa
     1621 atatgccatt tatagagata agataaatga aataatactt cagccaccag gtttttctgt
     1681 ctcacataca taagcagcat ttcattgcag atatgggact gattctgtgg cttaccttga
     1741 ttaacatctt ttggaagttt tgctagtgtg ctttcctttc tttactatgt ttctcagatt
     1801 cctttgtatc agggttttgg gtgtcactta ggttttgtcc atcagattct gtgagacacc
     1861 aggcatcgtt ttgaggatgt gggttataca catggagtgc ttctggaact atcagcccac
     1921 ttgaccaccc agtttgtgga agcacaggca agagtgttct tttctggtga ttctccaggc
     1981 catttaatac cctgcaatgt aattgtccct ctgtggctca catttcatta gtgagccatg
     2041 aaatcaactc agtgggacat agccagcatt tttgcatacc aggttgggct ataaaatatt
     2101 tctgttgtca ataaatttta aatgttttcc tgctaaacta a
//
