LOCUS       NM_001385               2122 bp    mRNA    linear   PRI 27-APR-2025
DEFINITION  Homo sapiens dihydropyrimidinase (DPYS), mRNA.
ACCESSION   NM_001385
VERSION     NM_001385.3
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 2122)
  AUTHORS   De Mattia,E., Polesel,J., Silvestri,M., Roncato,R., Scarabel,L.,
            Calza,S., Spina,M., Puglisi,F., Toffoli,G. and Cecchin,E.
  TITLE     The burden of rare variants in DPYS gene is a novel predictor of
            the risk of developing severe fluoropyrimidine-related toxicity
  JOURNAL   Hum Genomics 17 (1), 99 (2023)
   PUBMED   37946254
  REMARK    GeneRIF: The burden of rare variants in DPYS gene is a novel
            predictor of the risk of developing severe fluoropyrimidine-related
            toxicity.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 2122)
  AUTHORS   Hishinuma,E., Narita,Y., Rico,E.M.G., Ueda,A., Obuchi,K.,
            Tanaka,Y., Saito,S., Tadaka,S., Kinoshita,K., Maekawa,M., Mano,N.,
            Nakayoshi,T., Oda,A., Hirasawa,N. and Hiratsuka,M.
  TITLE     Functional Characterization of 12 Dihydropyrimidinase Allelic
            Variants in Japanese Individuals for the Prediction of
            5-Fluorouracil Treatment-Related Toxicity
  JOURNAL   Drug Metab Dispos 51 (2), 165-173 (2023)
   PUBMED   36414408
  REMARK    GeneRIF: Functional Characterization of 12 Dihydropyrimidinase
            Allelic Variants in Japanese Individuals for the Prediction of
            5-Fluorouracil Treatment-Related Toxicity.
REFERENCE   3  (bases 1 to 2122)
  AUTHORS   Haenig,C., Atias,N., Taylor,A.K., Mazza,A., Schaefer,M.H., Russ,J.,
            Riechers,S.P., Jain,S., Coughlin,M., Fontaine,J.F., Freibaum,B.D.,
            Brusendorf,L., Zenkner,M., Porras,P., Stroedicke,M., Schnoegl,S.,
            Arnsburg,K., Boeddrich,A., Pigazzini,L., Heutink,P., Taylor,J.P.,
            Kirstein,J., Andrade-Navarro,M.A., Sharan,R. and Wanker,E.E.
  TITLE     Interactome Mapping Provides a Network of Neurodegenerative Disease
            Proteins and Uncovers Widespread Protein Aggregation in Affected
            Brains
  JOURNAL   Cell Rep 32 (7), 108050 (2020)
   PUBMED   32814053
REFERENCE   4  (bases 1 to 2122)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   5  (bases 1 to 2122)
  AUTHORS   Basbous,J., Aze,A., Chaloin,L., Lebdy,R., Hodroj,D., Ribeyre,C.,
            Larroque,M., Shepard,C., Kim,B., Pruvost,A., Moreaux,J.,
            Maiorano,D., Mechali,M. and Constantinou,A.
  TITLE     Dihydropyrimidinase protects from DNA replication stress caused by
            cytotoxic metabolites
  JOURNAL   Nucleic Acids Res 48 (4), 1886-1904 (2020)
   PUBMED   31853544
  REMARK    GeneRIF: This study defines dihydropyrimidines as potentially
            cytotoxic metabolites that may offer an opportunity for
            therapeutic-targeting of dihydropyrimidinase activity in solid
            tumors.
REFERENCE   6  (bases 1 to 2122)
  AUTHORS   Fukada,M., Watakabe,I., Yuasa-Kawada,J., Kawachi,H., Kuroiwa,A.,
            Matsuda,Y. and Noda,M.
  TITLE     Molecular characterization of CRMP5, a novel member of the
            collapsin response mediator protein family
  JOURNAL   J Biol Chem 275 (48), 37957-37965 (2000)
   PUBMED   10956643
REFERENCE   7  (bases 1 to 2122)
  AUTHORS   Van Kuilenburg,A.B., Van Lenthe,H. and Van Gennip,A.H.
  TITLE     Radiochemical assay for determination of dihydropyrimidinase
            activity using reversed-phase high-performance liquid
            chromatography
  JOURNAL   J Chromatogr B Biomed Sci Appl 729 (1-2), 307-314 (1999)
   PUBMED   10410956
REFERENCE   8  (bases 1 to 2122)
  AUTHORS   Hamajima,N., Kouwaki,M., Vreken,P., Matsuda,K., Sumi,S., Imaeda,M.,
            Ohba,S., Kidouchi,K., Nonaka,M., Sasaki,M., Tamaki,N., Endo,Y., De
            Abreu,R., Rotteveel,J., van Kuilenburg,A., van Gennip,A., Togari,H.
            and Wada,Y.
  TITLE     Dihydropyrimidinase deficiency: structural organization,
            chromosomal localization, and mutation analysis of the human
            dihydropyrimidinase gene
  JOURNAL   Am J Hum Genet 63 (3), 717-726 (1998)
   PUBMED   9718352
REFERENCE   9  (bases 1 to 2122)
  AUTHORS   Hamajima,N., Matsuda,K., Sakata,S., Tamaki,N., Sasaki,M. and
            Nonaka,M.
  TITLE     A novel gene family defined by human dihydropyrimidinase and three
            related proteins with differential tissue distribution
  JOURNAL   Gene 180 (1-2), 157-163 (1996)
   PUBMED   8973361
REFERENCE   10 (bases 1 to 2122)
  AUTHORS   Naguib,F.N., el Kouni,M.H. and Cha,S.
  TITLE     Enzymes of uracil catabolism in normal and neoplastic human tissues
  JOURNAL   Cancer Res 45 (11 Pt 1), 5405-5412 (1985)
   PUBMED   3931905
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AP002847.2, D78011.1 and
            BC034395.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_001385.2.
            
            Summary: Dihydropyrimidinase catalyzes the conversion of
            5,6-dihydrouracil to 3-ureidopropionate in pyrimidine metabolism.
            Dihydropyrimidinase is expressed at a high level in liver and
            kidney as a major 2.5-kb transcript and a minor 3.8-kb transcript.
            Defects in the DPYS gene are linked to dihydropyrimidinuria.
            [provided by RefSeq, Jul 2008].
            
            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 :: ERR279848.5650.1, BC034395.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1968540 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000351513.7/ ENSP00000276651.2
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-6                 AP002847.2         111056-111061       c
            7-135               D78011.1           1-129
            136-2122            BC034395.1         94-2080
FEATURES             Location/Qualifiers
     source          1..2122
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="8"
                     /map="8q22.3"
     gene            1..2122
                     /gene="DPYS"
                     /gene_synonym="DHP; DHPase"
                     /note="dihydropyrimidinase"
                     /db_xref="GeneID:1807"
                     /db_xref="HGNC:HGNC:3013"
                     /db_xref="MIM:613326"
     exon            1..399
                     /gene="DPYS"
                     /gene_synonym="DHP; DHPase"
                     /inference="alignment:Splign:2.1.0"
     CDS             136..1695
                     /gene="DPYS"
                     /gene_synonym="DHP; DHPase"
                     /EC_number="3.5.2.2"
                     /note="dihydropyrimidine amidohydrolase; hydantoinase"
                     /codon_start=1
                     /product="dihydropyrimidinase"
                     /protein_id="NP_001376.1"
                     /db_xref="CCDS:CCDS6302.1"
                     /db_xref="GeneID:1807"
                     /db_xref="HGNC:HGNC:3013"
                     /db_xref="MIM:613326"
                     /translation="MAAPSRLLIRGGRVVNDDFSEVADVLVEDGVVRALGHDLLPPGG
                     APAGLRVLDAAGKLVLPGGIDTHTHMQFPFMGSRSIDDFHQGTKAALSGGTTMIIDFA
                     IPQKGGSLIEAFETWRSWADPKVCCDYSLHVAVTWWSDQVKEEMKILVQDKGVNSFKM
                     FMAYKDLYMVTDLELYEAFSRCKEIGAIAQVHAENGDLIAEGAKKMLALGITGPEGHE
                     LCRPEAVEAEATLRAITIASAVNCPLYIVHVMSKSAAKVIADARRDGKVVYGEPIAAS
                     LGTDGTHYWNKEWHHAAHHVMGPPLRPDPSTPDFLMNLLANDDLTTTGTDNCTFNTCQ
                     KALGKDDFTKIPNGVNGVEDRMSVIWEKGVHSGKMDENRFVAVTSTNAAKIFNLYPRK
                     GRIAVGSDADIVIWDPKGTRTISAKTHHQAVNFNIFEGMVCHGVPLVTISRGKVVYEA
                     GVFSVTAGDGKFIPRKPFAEYIYKRIKQRDRTCTPTPVERAPYKGEVATLKSRVTKED
                     ATAGTRKQAHP"
     exon            400..558
                     /gene="DPYS"
                     /gene_synonym="DHP; DHPase"
                     /inference="alignment:Splign:2.1.0"
     exon            559..738
                     /gene="DPYS"
                     /gene_synonym="DHP; DHPase"
                     /inference="alignment:Splign:2.1.0"
     exon            739..928
                     /gene="DPYS"
                     /gene_synonym="DHP; DHPase"
                     /inference="alignment:Splign:2.1.0"
     exon            929..1085
                     /gene="DPYS"
                     /gene_synonym="DHP; DHPase"
                     /inference="alignment:Splign:2.1.0"
     exon            1086..1227
                     /gene="DPYS"
                     /gene_synonym="DHP; DHPase"
                     /inference="alignment:Splign:2.1.0"
     exon            1228..1370
                     /gene="DPYS"
                     /gene_synonym="DHP; DHPase"
                     /inference="alignment:Splign:2.1.0"
     exon            1371..1578
                     /gene="DPYS"
                     /gene_synonym="DHP; DHPase"
                     /inference="alignment:Splign:2.1.0"
     exon            1579..1709
                     /gene="DPYS"
                     /gene_synonym="DHP; DHPase"
                     /inference="alignment:Splign:2.1.0"
     exon            1710..2122
                     /gene="DPYS"
                     /gene_synonym="DHP; DHPase"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2098..2103
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DPYS"
                     /gene_synonym="DHP; DHPase"
                     /note="hexamer: AATAAA"
     polyA_site      2122
                     /gene="DPYS"
                     /gene_synonym="DHP; DHPase"
                     /note="major polyA site"
ORIGIN      
        1 ggatttgcag cctgaggcag agctcggggg ctgtcggtgg ggaccttgca ggagggcacc
       61 ccaagcccgc ccggcccgcc caacccagcc cctgcgcgca gcccgggccg agtaggaccc
      121 cgcgcgcccc tcgctatggc ggcgccctcg cggctcctga tccgcggggg tcgcgtggtc
      181 aacgatgact tctcggaggt ggccgacgtg ctggtggagg acggcgtggt gcgggcactc
      241 gggcacgacc tgctgcctcc cgggggcgct cctgcggggc tgcgggtcct cgacgccgcc
      301 ggcaagctcg tcctgcccgg aggcatcgac acacacacgc acatgcagtt ccccttcatg
      361 ggctcgcggt ccatcgacga cttccaccag ggcaccaagg ctgctctctc aggaggcacc
      421 accatgatta ttgatttcgc cattcctcag aaaggtggct ccctcattga ggccttcgag
      481 acctggcgaa gctgggctga tcccaaagtt tgctgcgact acagccttca tgtggcagtg
      541 acgtggtgga gtgaccaggt taaagaagaa atgaaaatcc ttgtgcaaga taaaggtgtt
      601 aactctttca agatgtttat ggcctataaa gatctgtaca tggtgacaga cctggagctg
      661 tacgaagcct tctctcggtg caaggaaatt ggagcaattg cccaggtcca tgcggaaaat
      721 ggagacttaa ttgcagaggg agcaaagaag atgttggctc tggggataac aggccctgag
      781 ggccacgagc tgtgccgccc agaggcagtg gaggcagagg ccacgctgag agccatcacc
      841 atagccagcg ctgtgaactg tcctctctac attgtgcatg tgatgagcaa gtctgcagct
      901 aaggtgatag cggatgcaag gagagatggg aaggtggtct atggtgaacc catagcagcc
      961 agtcttggca cagatggcac tcactactgg aataaagaat ggcaccatgc agcccaccat
     1021 gtcatgggtc cacctttgcg accagacccc tcaacacccg acttcctcat gaatctgttg
     1081 gctaatgatg atctaaccac aacagggact gataactgca ctttcaacac ctgccagaaa
     1141 gctcttggga aggatgattt taccaagatc cccaatgggg tgaatggtgt tgaagatcgg
     1201 atgtccgtaa tatgggaaaa aggcgtgcat agtggtaaaa tggatgaaaa cagatttgtg
     1261 gcagttacca gcacaaatgc agccaaaatt tttaatctct atccaagaaa aggaagaata
     1321 gctgtaggat cagatgctga cattgttatt tgggacccaa aaggcacaag gactatctca
     1381 gcaaaaactc atcatcaggc tgttaacttc aacattttcg agggcatggt ttgccacggg
     1441 gtgccccttg tgactatttc aagaggcaaa gtggtatatg aagccggagt gttcagtgtc
     1501 acggcaggag atgggaagtt tattcctcga aaaccatttg ctgaatatat ttacaaacga
     1561 ataaagcagc gagaccggac ttgcacacct acccctgtgg agcgtgcacc ctataaggga
     1621 gaagtcgcca cactgaaatc cagagtgaca aaagaagatg ccacagcagg gaccaggaaa
     1681 caggcccacc cctgaagtgt gtgccatcgg taaaaaaatc agaggaaagg aggctgccat
     1741 tcccttcaca gccaaacatt gtcaacccat ggagaagcag gccttattca actccctagg
     1801 atcctttaga aaaaattcac cactataggc ttctttgatt ttctttcaga agcaattgct
     1861 gtctttctca ctgtgttttt gttgctgcat aagattgaag gtataaattt atattattgt
     1921 gatggaaagg ctgtgtggaa attcattgat gatactttaa aatgtcatct ttgcttgtac
     1981 tagatttctt acttagaatt tttaaaaatc attttcttgt ttaaatagtt tcttttttta
     2041 aaaaaatggt tacattagtt ttaaaatagc tctgtgattt tactttttat tgtaattaat
     2101 aaacattgag atcttcattt ta
//
