ID   DPYS_MOUSE              Reviewed;         519 AA.
AC   Q9EQF5; Q99PP1; Q9DBK3; Q9DBP7;
DT   06-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT   06-JUN-2002, sequence version 2.
DT   24-JAN-2024, entry version 165.
DE   RecName: Full=Dihydropyrimidinase;
DE            Short=DHP;
DE            Short=DHPase;
DE            EC=3.5.2.2 {ECO:0000250|UniProtKB:Q55DL0};
DE   AltName: Full=Dihydropyrimidine amidohydrolase;
DE   AltName: Full=Hydantoinase;
GN   Name=Dpys;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Swiss Webster / NIH; TISSUE=Embryo;
RX   PubMed=10956643; DOI=10.1074/jbc.m003277200;
RA   Fukada M., Watakabe I., Yuasa-Kawada J., Kawachi H., Kuroiwa A.,
RA   Matsuda Y., Noda M.;
RT   "Molecular characterization of CRMP5, a novel member of the collapsin
RT   response mediator protein family.";
RL   J. Biol. Chem. 275:37957-37965(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Liver;
RA   Chang C.J., Huang C.J., Yang Y.S., Wu T.K.;
RT   "Molecular cloning, nucleotide sequencing, characterization and
RT   overexpression of dihydropyrimidinase from mouse liver.";
RL   Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Liver, and Lung;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Liver;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [6]
RP   SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-256, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA   Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA   Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT   "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT   pathways.";
RL   Mol. Cell 50:919-930(2013).
CC   -!- FUNCTION: Catalyzes the second step of the reductive pyrimidine
CC       degradation, the reversible hydrolytic ring opening of
CC       dihydropyrimidines. Can catalyze the ring opening of 5,6-dihydrouracil
CC       to N-carbamyl-alanine and of 5,6-dihydrothymine to N-carbamyl-amino
CC       isobutyrate (By similarity). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=5,6-dihydrouracil + H2O = 3-(carbamoylamino)propanoate + H(+);
CC         Xref=Rhea:RHEA:16121, ChEBI:CHEBI:11892, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15901; EC=3.5.2.2;
CC         Evidence={ECO:0000250|UniProtKB:Q55DL0};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:Q55DL0};
CC       Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:Q55DL0};
CC   -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:Q55DL0}.
CC   -!- PTM: Carboxylation allows a single lysine to coordinate two zinc ions.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC       Hydantoinase/dihydropyrimidinase family. {ECO:0000305}.
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DR   EMBL; AF249296; AAG37999.1; -; mRNA.
DR   EMBL; AF227731; AAK00644.1; -; mRNA.
DR   EMBL; AK004822; BAB23593.1; -; mRNA.
DR   EMBL; AK004899; BAB23654.1; -; mRNA.
DR   EMBL; BC037086; AAH37086.1; -; mRNA.
DR   CCDS; CCDS27445.1; -.
DR   RefSeq; NP_001157938.1; NM_001164466.1.
DR   RefSeq; NP_073559.3; NM_022722.3.
DR   AlphaFoldDB; Q9EQF5; -.
DR   SMR; Q9EQF5; -.
DR   BioGRID; 211101; 2.
DR   STRING; 10090.ENSMUSP00000022915; -.
DR   MEROPS; M38.973; -.
DR   GlyGen; Q9EQF5; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; Q9EQF5; -.
DR   PhosphoSitePlus; Q9EQF5; -.
DR   SwissPalm; Q9EQF5; -.
DR   jPOST; Q9EQF5; -.
DR   MaxQB; Q9EQF5; -.
DR   PaxDb; 10090-ENSMUSP00000022915; -.
DR   PeptideAtlas; Q9EQF5; -.
DR   ProteomicsDB; 277401; -.
DR   Antibodypedia; 13364; 330 antibodies from 27 providers.
DR   DNASU; 64705; -.
DR   Ensembl; ENSMUST00000022915.11; ENSMUSP00000022915.4; ENSMUSG00000022304.14.
DR   Ensembl; ENSMUST00000110306.9; ENSMUSP00000105935.2; ENSMUSG00000022304.14.
DR   GeneID; 64705; -.
DR   KEGG; mmu:64705; -.
DR   UCSC; uc007vok.2; mouse.
DR   AGR; MGI:1928679; -.
DR   CTD; 1807; -.
DR   MGI; MGI:1928679; Dpys.
DR   VEuPathDB; HostDB:ENSMUSG00000022304; -.
DR   eggNOG; KOG2584; Eukaryota.
DR   GeneTree; ENSGT01030000234527; -.
DR   HOGENOM; CLU_015572_2_2_1; -.
DR   InParanoid; Q9EQF5; -.
DR   OMA; SAETHHM; -.
DR   OrthoDB; 1772494at2759; -.
DR   PhylomeDB; Q9EQF5; -.
DR   TreeFam; TF314706; -.
DR   BRENDA; 3.5.2.2; 3474.
DR   Reactome; R-MMU-73621; Pyrimidine catabolism.
DR   BioGRID-ORCS; 64705; 1 hit in 77 CRISPR screens.
DR   ChiTaRS; Dpys; mouse.
DR   PRO; PR:Q9EQF5; -.
DR   Proteomes; UP000000589; Chromosome 15.
DR   RNAct; Q9EQF5; Protein.
DR   Bgee; ENSMUSG00000022304; Expressed in left lobe of liver and 42 other cell types or tissues.
DR   ExpressionAtlas; Q9EQF5; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IDA:MGI.
DR   GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR   GO; GO:0016597; F:amino acid binding; ISS:BHF-UCL.
DR   GO; GO:0004157; F:dihydropyrimidinase activity; IDA:MGI.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0051219; F:phosphoprotein binding; IPI:BHF-UCL.
DR   GO; GO:0002059; F:thymine binding; ISS:BHF-UCL.
DR   GO; GO:0002058; F:uracil binding; ISS:BHF-UCL.
DR   GO; GO:0008270; F:zinc ion binding; ISS:BHF-UCL.
DR   GO; GO:0019482; P:beta-alanine metabolic process; ISS:BHF-UCL.
DR   GO; GO:0006248; P:CMP catabolic process; IDA:MGI.
DR   GO; GO:0006249; P:dCMP catabolic process; IDA:MGI.
DR   GO; GO:0046074; P:dTMP catabolic process; ISO:MGI.
DR   GO; GO:0046079; P:dUMP catabolic process; IDA:MGI.
DR   GO; GO:0006208; P:pyrimidine nucleobase catabolic process; ISO:MGI.
DR   GO; GO:0006210; P:thymine catabolic process; ISS:BHF-UCL.
DR   GO; GO:0046050; P:UMP catabolic process; IDA:MGI.
DR   GO; GO:0006212; P:uracil catabolic process; ISS:BHF-UCL.
DR   GO; GO:0019860; P:uracil metabolic process; ISO:MGI.
DR   CDD; cd01314; D-HYD; 1.
DR   Gene3D; 3.20.20.140; Metal-dependent hydrolases; 1.
DR   Gene3D; 2.30.40.10; Urease, subunit C, domain 1; 1.
DR   InterPro; IPR006680; Amidohydro-rel.
DR   InterPro; IPR011778; Hydantoinase/dihydroPyrase.
DR   InterPro; IPR011059; Metal-dep_hydrolase_composite.
DR   InterPro; IPR032466; Metal_Hydrolase.
DR   NCBIfam; TIGR02033; D-hydantoinase; 1.
DR   PANTHER; PTHR11647:SF50; DIHYDROPYRIMIDINASE; 1.
DR   PANTHER; PTHR11647; HYDRANTOINASE/DIHYDROPYRIMIDINASE FAMILY MEMBER; 1.
DR   Pfam; PF01979; Amidohydro_1; 1.
DR   SUPFAM; SSF51338; Composite domain of metallo-dependent hydrolases; 2.
DR   SUPFAM; SSF51556; Metallo-dependent hydrolases; 1.
DR   Genevisible; Q9EQF5; MM.
PE   1: Evidence at protein level;
KW   Hydrolase; Metal-binding; Phosphoprotein; Reference proteome; Zinc.
FT   CHAIN           1..519
FT                   /note="Dihydropyrimidinase"
FT                   /id="PRO_0000165907"
FT   BINDING         67
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P903"
FT   BINDING         69
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P903"
FT   BINDING         159
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /note="via carbamate group"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P903"
FT   BINDING         159
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /note="via carbamate group"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P903"
FT   BINDING         164
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P903"
FT   BINDING         192
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P903"
FT   BINDING         248
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P903"
FT   BINDING         326
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P903"
FT   BINDING         347
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P903"
FT   MOD_RES         79
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q14117"
FT   MOD_RES         159
FT                   /note="N6-carboxylysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P903"
FT   MOD_RES         256
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         510
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9EQF6"
FT   CONFLICT        13
FT                   /note="R -> L (in Ref. 1; AAG37999 and 4; AAH37086)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        37
FT                   /note="R -> P (in Ref. 2; AAK00644)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        43
FT                   /note="E -> G (in Ref. 2; AAK00644)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        206
FT                   /note="M -> T (in Ref. 3; BAB23654)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        299
FT                   /note="P -> L (in Ref. 2; AAK00644)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        366
FT                   /note="S -> N (in Ref. 2; AAK00644)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   519 AA;  56725 MW;  F2C53D40EC120ABD CRC64;
     MAPQGRLLIR GGRIVNDDFS QVADVLVEDG VVRALGRDLL PPEDASRGLR ILDAAGKLVL
     PGGIDTHTHM QFPFMGSQSV DDFYQGTKAA LAGGTTMIID FAIPQKGSSL IEAFETWRNW
     ADPKVCCDYS LHVAVTWWSD KVKEEMKTLA RDKGVNSFKM FMAYKGLYMV QDEQLYAAFS
     QCKEIGAIAQ VHAENGDLIA EGAKKMLALG ITGPEGHELC RPEAVEAEAT LRAITIASAV
     NCPLYVVHVM SKSAAKVVAD ARRAGNVVYG EPIAAGLGTD GRQYWSEEWS HAAHHVMGPP
     LRPDPLTPGF LMDLLANGDL TTTGSDNCTF NTCQKALGKD DFTKIPNGVN GVEDRMSVIW
     EKGVHSGKMD ENRFVAVTST NAAKIFNLYP KKGRIAVGSD ADIVIWDPEA TRRISAKTHH
     QAVNFNIFEG MVCHGVPLVT ISRGRVVYEA GVFNVTAGHG KFIPRQPFAE YIYKRIKQRD
     QTCTPVPVKR APYKGEVTTL KARETKEDDT AGTRMQGHS
//