DUT_MOUSE
ID DUT_MOUSE Reviewed; 162 AA.
AC Q9CQ43; Q8VCG1; Q9JJ44;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Deoxyuridine 5'-triphosphate nucleotidohydrolase;
DE Short=dUTPase;
DE EC=3.6.1.23 {ECO:0000250|UniProtKB:P33316};
GN Name=Dut; Synonyms=Dutp;
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] (ISOFORM 1).
RA Kan L., Varanasi U., Zhu Y., Qi C., Reddy J.K.;
RT "Mouse dUTPase cloning and genomic structural analysis.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J;
RC TISSUE=Bone marrow, Muellerian duct, Ovary, Spleen, and Uterus;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=FVB/N, and FVB/N-3; TISSUE=Mammary tumor, and Salivary gland;
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].
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 FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30987342; DOI=10.3390/biom9040136;
RA Palinkas H.L., Racz G.A., Gal Z., Hoffmann O.I., Tihanyi G., Rona G.,
RA Gocza E., Hiripi L., Vertessy B.G.;
RT "CRISPR/Cas9-Mediated Knock-Out of dUTPase in Mice Leads to Early Embryonic
RT Lethality.";
RL Biomolecules 9:0-0(2019).
CC -!- FUNCTION: Catalyzes the cleavage of 2'-deoxyuridine 5'-triphosphate
CC (dUTP) into 2'-deoxyuridine 5'-monophosphate (dUMP) and inorganic
CC pyrophosphate and through its action efficiently prevents uracil
CC misincorporation into DNA and at the same time provides dUMP, the
CC substrate for de novo thymidylate biosynthesis (By similarity).
CC Inhibits peroxisome proliferator-activated receptor (PPAR) activity by
CC binding of its N-terminal to PPAR, preventing the latter's dimerization
CC with retinoid X receptor (By similarity). Essential for embryonic
CC development (PubMed:30987342). {ECO:0000250|UniProtKB:P33316,
CC ECO:0000250|UniProtKB:P70583, ECO:0000269|PubMed:30987342}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dUTP + H2O = diphosphate + dUMP + H(+); Xref=Rhea:RHEA:10248,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:61555, ChEBI:CHEBI:246422; EC=3.6.1.23;
CC Evidence={ECO:0000250|UniProtKB:P33316};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P33316};
CC -!- PATHWAY: Pyrimidine metabolism; dUMP biosynthesis; dUMP from dCTP (dUTP
CC route): step 2/2. {ECO:0000250|UniProtKB:P33316}.
CC -!- SUBUNIT: Homotrimer. {ECO:0000250|UniProtKB:P33316}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P33316}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9CQ43-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9CQ43-2; Sequence=VSP_061339;
CC -!- PTM: Phosphorylated in vivo on Ser-11, a reaction that can be catalyzed
CC in vitro by CDC2. {ECO:0000250|UniProtKB:P33316}.
CC -!- DISRUPTION PHENOTYPE: Embryos reach the blastocyst stage, however, they
CC die shortly after implantation and analysis of pre-implantation embryos
CC indicates perturbed growth of both inner cell mass and trophectoderm.
CC {ECO:0000269|PubMed:30987342}.
CC -!- SIMILARITY: Belongs to the dUTPase family. {ECO:0000305}.
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DR EMBL; AF091101; AAF74514.1; -; mRNA.
DR EMBL; AK003076; BAB22551.1; -; mRNA.
DR EMBL; AK011407; BAB27599.1; -; mRNA.
DR EMBL; AK077244; BAC36706.1; -; mRNA.
DR EMBL; AK152459; BAE31237.1; -; mRNA.
DR EMBL; AK153285; BAE31868.1; -; mRNA.
DR EMBL; AK135438; BAE22532.1; -; mRNA.
DR EMBL; GL456092; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC053693; AAH53693.1; -; mRNA.
DR EMBL; BC019979; AAH19979.1; -; mRNA.
DR CCDS; CCDS16675.1; -. [Q9CQ43-1]
DR CCDS; CCDS50695.1; -. [Q9CQ43-2]
DR RefSeq; NP_001153118.1; NM_001159646.1.
DR RefSeq; NP_076084.2; NM_023595.6.
DR SMR; Q9CQ43; -.
DR IntAct; Q9CQ43; 3.
DR STRING; 10090.ENSMUSP00000080767; -.
DR REPRODUCTION-2DPAGE; IPI00467266; -.
DR EPD; Q9CQ43; -.
DR jPOST; Q9CQ43; -.
DR MaxQB; Q9CQ43; -.
DR PeptideAtlas; Q9CQ43; -.
DR PRIDE; Q9CQ43; -.
DR ProteomicsDB; 340884; -.
DR ProteomicsDB; 343269; -.
DR Antibodypedia; 24524; 384 antibodies from 31 providers.
DR DNASU; 110074; -.
DR Ensembl; ENSMUST00000051605; ENSMUSP00000057854; ENSMUSG00000027203. [Q9CQ43-1]
DR Ensembl; ENSMUST00000082122; ENSMUSP00000080767; ENSMUSG00000027203. [Q9CQ43-2]
DR GeneID; 110074; -.
DR KEGG; mmu:110074; -.
DR UCSC; uc008mck.1; mouse.
DR UCSC; uc008mcl.2; mouse. [Q9CQ43-1]
DR CTD; 1854; -.
DR MGI; MGI:1346051; Dut.
DR VEuPathDB; HostDB:ENSMUSG00000027203; -.
DR eggNOG; KOG3370; Eukaryota.
DR GeneTree; ENSGT00390000018390; -.
DR HOGENOM; CLU_068508_2_1_1; -.
DR OMA; ICYPDLE; -.
DR OrthoDB; 1495752at2759; -.
DR TreeFam; TF105416; -.
DR Reactome; R-MMU-499943; Interconversion of nucleotide di- and triphosphates.
DR UniPathway; UPA00610; UER00666.
DR BioGRID-ORCS; 110074; 28 hits in 73 CRISPR screens.
DR ChiTaRS; Dut; mouse.
DR Proteomes; UP000000589; Chromosome 2.
DR Bgee; ENSMUSG00000027203; Expressed in primitive streak and 245 other tissues.
DR ExpressionAtlas; Q9CQ43; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0004170; F:dUTP diphosphatase activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0042975; F:peroxisome proliferator activated receptor binding; ISO:MGI.
DR GO; GO:0032556; F:pyrimidine deoxyribonucleotide binding; ISO:MGI.
DR GO; GO:0030547; F:signaling receptor inhibitor activity; ISO:MGI.
DR GO; GO:0006231; P:dTMP biosynthetic process; ISO:MGI.
DR GO; GO:0006226; P:dUMP biosynthetic process; ISO:MGI.
DR GO; GO:0046081; P:dUTP catabolic process; ISO:MGI.
DR GO; GO:0043254; P:regulation of protein-containing complex assembly; ISO:MGI.
DR CDD; cd07557; trimeric_dUTPase; 1.
DR Gene3D; 2.70.40.10; -; 1.
DR InterPro; IPR008181; dUTPase.
DR InterPro; IPR029054; dUTPase-like.
DR InterPro; IPR036157; dUTPase-like_sf.
DR InterPro; IPR033704; dUTPase_trimeric.
DR PANTHER; PTHR11241; PTHR11241; 1.
DR Pfam; PF00692; dUTPase; 1.
DR SUPFAM; SSF51283; SSF51283; 1.
DR TIGRFAMs; TIGR00576; dut; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Hydrolase; Magnesium; Metal-binding;
KW Nucleotide metabolism; Nucleus; Phosphoprotein; Reference proteome;
KW Transit peptide.
FT CHAIN 1..162
FT /note="Deoxyuridine 5'-triphosphate nucleotidohydrolase"
FT /id="PRO_0000454313"
FT BINDING 83..85
FT /ligand="dUTP"
FT /ligand_id="ChEBI:CHEBI:61555"
FT /evidence="ECO:0000250|UniProtKB:P33316"
FT BINDING 97..103
FT /ligand="dUTP"
FT /ligand_id="ChEBI:CHEBI:61555"
FT /evidence="ECO:0000250|UniProtKB:P33316"
FT BINDING 108
FT /ligand="dUTP"
FT /ligand_id="ChEBI:CHEBI:61555"
FT /evidence="ECO:0000250|UniProtKB:P33316"
FT BINDING 151
FT /ligand="dUTP"
FT /ligand_id="ChEBI:CHEBI:61555"
FT /evidence="ECO:0000250|UniProtKB:P33316"
FT BINDING 156..157
FT /ligand="dUTP"
FT /ligand_id="ChEBI:CHEBI:61555"
FT /evidence="ECO:0000250|UniProtKB:P33316"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P33316"
FT VAR_SEQ 1..5
FT /note="MPCSE -> MPLLSVLLRARLQAALLRGRALGSARSRSCRGSRGAPAGSARA
FT (in isoform 2)"
FT /id="VSP_061339"
FT CONFLICT 35
FT /note="A -> T (in Ref. 1; AAF74514)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 162 AA; 17385 MW; C9C3390EA9A4E0A4 CRC64;
MPCSEDAAAV SASKRARAED GASLRFVRLS EHATAPTRGS ARAAGYDLFS AYDYTISPME
KAIVKTDIQI AVPSGCYGRV APRSGLAVKH FIDVGAGVID EDYRGNVGVV LFNFGKEKFE
VKKGDRIAQL ICERISYPDL EEVQTLDDTE RGSGGFGSTG KN
