DUT_HUMAN
ID DUT_HUMAN Reviewed; 252 AA.
AC P33316; A8K650; B4DPR5; O14785; Q16708; Q16860; Q6FHN1; Q6NSA3; Q96Q81;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 21-SEP-2011, sequence version 4.
DT 03-AUG-2022, entry version 219.
DE RecName: Full=Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial {ECO:0000303|PubMed:8631816};
DE Short=dUTPase {ECO:0000303|PubMed:8631816};
DE EC=3.6.1.23 {ECO:0000269|PubMed:17880943, ECO:0000269|PubMed:8631816, ECO:0000269|PubMed:8805593};
DE AltName: Full=dUTP pyrophosphatase;
DE Flags: Precursor;
GN Name=DUT;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 70-93 (ISOFORM
RP 3), PROTEIN SEQUENCE OF N-TERMINUS, PROTEIN SEQUENCE OF 94-115; 119-128;
RP 133-151; 156-169; 180-206 AND 217-241 (ISOFORMS 2/3), CLEAVAGE OF INITIATOR
RP METHIONINE (ISOFORM 2), FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=T-cell;
RX PubMed=8631816; DOI=10.1074/jbc.271.13.7745;
RA Ladner R.D., McNulty D.E., Carr S.A., Roberts G.D., Caradonna S.J.;
RT "Characterization of distinct nuclear and mitochondrial forms of human
RT deoxyuridine triphosphate nucleotidohydrolase.";
RL J. Biol. Chem. 271:7745-7751(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=9070952; DOI=10.1006/geno.1996.4540;
RA Cohen D., Heng H.H.Q., Shi X.-M., McIntosh E.M., Tsui L.-C., Pearlman R.E.;
RT "Assignment of the human dUTPase gene (DUT) to chromosome 15q15-q21. 1 by
RT fluorescence in situ hybridization.";
RL Genomics 40:213-215(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 2 AND 3).
RA Pearlman R.E.;
RT "Human genomic nuclear and mitochondria dUTPase gene.";
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE [GENOMIC DNA]
RP OF 1-139 (ISOFORMS 2 AND 3), SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Lung fibroblast;
RX PubMed=9228092; DOI=10.1074/jbc.272.30.19072;
RA Ladner R.D., Caradonna S.J.;
RT "The human dUTPase gene encodes both nuclear and mitochondrial isoforms.
RT Differential expression of the isoforms and characterization of a cDNA
RT encoding the mitochondrial species.";
RL J. Biol. Chem. 272:19072-19080(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Chano T., Okabe H., Baldini N., Lapucci C., Scotlandi K., Serra M.,
RA Saeki Y.;
RT "Unknown transcriptional variant of nuclear dUTPase in human
RT osteosarcoma.";
RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-100.
RG NIEHS SNPs program;
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Brain, Eye, and Urinary bladder;
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 [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 112-252.
RX PubMed=1325640; DOI=10.1073/pnas.89.17.8020;
RA McIntosh E.M., Ager D.D., Gadsden M.H., Haynes R.H.;
RT "Human dUTP pyrophosphatase: cDNA sequence and potential biological
RT importance of the enzyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:8020-8024(1992).
RN [12]
RP ERRATUM OF PUBMED:1325640.
RA McIntosh E.M., Ager D.D., Gadsden M.H., Haynes R.H.;
RL Proc. Natl. Acad. Sci. U.S.A. 90:4328-4328(1993).
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 112-252, PARTIAL PROTEIN SEQUENCE, AND
RP PHOSPHORYLATION.
RC TISSUE=Lymphocyte;
RX PubMed=8389461; DOI=10.1073/pnas.90.11.4991;
RA Strahler J.R., Zhu X.-X., Wang Y.K., Hora N., Andrews P.C., Roseman N.A.,
RA Neel J.V., Turka L., Hanash S.M.;
RT "Maturation stage and proliferation-dependent expression of dUTPase in
RT human T cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:4991-4995(1993).
RN [14]
RP PROTEIN SEQUENCE OF N-TERMINUS, PHOSPHORYLATION AT SER-11 (ISOFORM 2),
RP MUTAGENESIS OF SER-99, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=8631817; DOI=10.1074/jbc.271.13.7752;
RA Ladner R.D., Carr S.A., Huddleston M.J., McNulty D.E., Caradonna S.J.;
RT "Identification of a consensus cyclin-dependent kinase phosphorylation site
RT unique to the nuclear form of human deoxyuridine triphosphate
RT nucleotidohydrolase.";
RL J. Biol. Chem. 271:7752-7757(1996).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-11 (ISOFORM 2), AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11 (ISOFORM 2), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88 AND SER-99, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [23]
RP CLEAVAGE OF TRANSIT PEPTIDE [LARGE SCALE ANALYSIS] AFTER GLY-69, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 112-252 IN COMPLEX WITH SUBSTRATE
RP AND MAGNESIUM IONS, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, PATHWAY, AND
RP SUBUNIT.
RX PubMed=8805593; DOI=10.1016/s0969-2126(96)00114-1;
RA Mol C.D., Harris J.M., McIntosh E.M., Tainer J.A.;
RT "Human dUTP pyrophosphatase: uracil recognition by a beta hairpin and
RT active sites formed by three separate subunits.";
RL Structure 4:1077-1092(1996).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 89-252 (ISOFORM 2) IN COMPLEX WITH
RP SUBSTRATE ANALOG AND MAGNESIUM IONS, FUNCTION, CATALYTIC ACTIVITY,
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBUNIT.
RX PubMed=17880943; DOI=10.1016/j.febslet.2007.09.005;
RA Varga B., Barabas O., Kovari J., Toth J., Hunyadi-Gulyas E., Klement E.,
RA Medzihradszky K.F., Toelgyesi F., Fidy J., Vertessy B.G.;
RT "Active site closure facilitates juxtaposition of reactant atoms for
RT initiation of catalysis by human dUTPase.";
RL FEBS Lett. 581:4783-4788(2007).
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 (PubMed:17880943,
CC PubMed:8631816, PubMed:8805593). Inhibits peroxisome proliferator-
CC activated receptor (PPAR) activity by binding of its N-terminal to
CC PPAR, preventing the latter's dimerization with retinoid X receptor (By
CC similarity). Essential for embryonic development (By similarity).
CC {ECO:0000250|UniProtKB:P70583, ECO:0000250|UniProtKB:Q9CQ43,
CC ECO:0000269|PubMed:17880943, ECO:0000269|PubMed:8631816,
CC ECO:0000269|PubMed:8805593}.
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:0000269|PubMed:17880943, ECO:0000269|PubMed:8631816,
CC ECO:0000269|PubMed:8805593};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:8805593};
CC -!- ACTIVITY REGULATION: Phosphorylation is necessary for activity.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.5 uM for dUTP {ECO:0000269|PubMed:8631816};
CC Note=kM is identical for both isoform 2 and isoform 3.
CC {ECO:0000269|PubMed:8631816};
CC -!- PATHWAY: Pyrimidine metabolism; dUMP biosynthesis; dUMP from dCTP (dUTP
CC route): step 2/2. {ECO:0000269|PubMed:8631816,
CC ECO:0000269|PubMed:8805593}.
CC -!- SUBUNIT: Homotrimer. {ECO:0000269|PubMed:17880943,
CC ECO:0000269|PubMed:8805593}.
CC -!- INTERACTION:
CC P33316; Q6ZVK8: NUDT18; NbExp=3; IntAct=EBI-353224, EBI-740486;
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000269|PubMed:8631816,
CC ECO:0000269|PubMed:9070952}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Mitochondrion
CC {ECO:0000269|PubMed:8631816, ECO:0000269|PubMed:9070952}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=3; Synonyms=DUT-M;
CC IsoId=P33316-3; Sequence=Displayed;
CC Name=2; Synonyms=DUT-N;
CC IsoId=P33316-2; Sequence=VSP_001324;
CC -!- TISSUE SPECIFICITY: Found in a variety of tissues. Isoform 3 expression
CC is constitutive, while isoform 2 expression correlates with the onset
CC of DNA replication (at protein level). Isoform 2 degradation coincides
CC with the cessation of nuclear DNA replication (at protein level).
CC {ECO:0000269|PubMed:9228092}.
CC -!- PTM: Nuclear isoform 2 is phosphorylated in vivo on Ser-11, a reaction
CC that can be catalyzed in vitro by CDC2. Phosphorylation in mature T-
CC cells occurs in a cell cycle-dependent manner. Isoform 3 is not
CC phosphorylated. {ECO:0000269|PubMed:8389461}.
CC -!- MISCELLANEOUS: Each trimer binds three substrate molecules. The ligands
CC are bound between subunits, and for each substrate molecule, residues
CC from adjacent subunits contribute to the binding interactions.
CC -!- MISCELLANEOUS: [Isoform 2]: Major isoform. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the dUTPase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB71393.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAB93866.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAB94642.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/dut/";
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DR EMBL; U31930; AAC50418.1; -; mRNA.
DR EMBL; U62891; AAC51123.1; -; mRNA.
DR EMBL; AF018432; AAB71393.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AF018429; AAB71393.1; JOINED; Genomic_DNA.
DR EMBL; AF018430; AAB71393.1; JOINED; Genomic_DNA.
DR EMBL; AF018431; AAB71393.1; JOINED; Genomic_DNA.
DR EMBL; AF018432; AAB71394.1; -; Genomic_DNA.
DR EMBL; AF018429; AAB71394.1; JOINED; Genomic_DNA.
DR EMBL; AF018430; AAB71394.1; JOINED; Genomic_DNA.
DR EMBL; AF018431; AAB71394.1; JOINED; Genomic_DNA.
DR EMBL; U90223; AAB94642.1; ALT_FRAME; mRNA.
DR EMBL; U90224; AAB93866.1; ALT_FRAME; Genomic_DNA.
DR EMBL; U90224; AAB93867.1; -; Genomic_DNA.
DR EMBL; AB049113; BAB13724.1; -; mRNA.
DR EMBL; AY935242; AAX14045.1; -; Genomic_DNA.
DR EMBL; AK291515; BAF84204.1; -; mRNA.
DR EMBL; AK312122; BAG35058.1; -; mRNA.
DR EMBL; CR541720; CAG46521.1; -; mRNA.
DR EMBL; CR541781; CAG46580.1; -; mRNA.
DR EMBL; CH471082; EAW77350.1; -; Genomic_DNA.
DR EMBL; AK298464; BAG60677.1; -; mRNA.
DR EMBL; BC033645; AAH33645.1; -; mRNA.
DR EMBL; BC070339; AAH70339.1; -; mRNA.
DR EMBL; BC110377; AAI10378.1; -; mRNA.
DR EMBL; M89913; AAA58444.1; -; mRNA.
DR EMBL; L11877; AAA36801.1; -; mRNA.
DR CCDS; CCDS32231.1; -. [P33316-3]
DR CCDS; CCDS45255.1; -. [P33316-2]
DR PIR; A46256; A46256.
DR PIR; G02777; G02777.
DR RefSeq; NP_001020419.1; NM_001025248.1. [P33316-3]
DR RefSeq; NP_001020420.1; NM_001025249.1.
DR RefSeq; NP_001317215.1; NM_001330286.1.
DR RefSeq; NP_001939.1; NM_001948.3. [P33316-2]
DR PDB; 1Q5H; X-ray; 2.00 A; A/B/C=112-252.
DR PDB; 1Q5U; X-ray; 2.00 A; X/Y/Z=112-252.
DR PDB; 2HQU; X-ray; 2.20 A; A/B/C=94-252.
DR PDB; 3ARA; X-ray; 1.70 A; A/B/C=94-252.
DR PDB; 3ARN; X-ray; 1.80 A; A/B/C=94-252.
DR PDB; 3EHW; X-ray; 1.80 A; A/B/C/X/Y/Z=94-252.
DR PDB; 4MZ5; X-ray; 2.10 A; A/C=97-109.
DR PDB; 4MZ6; X-ray; 1.88 A; A/C=97-109.
DR PDB; 5H4J; X-ray; 1.80 A; A=94-252.
DR PDBsum; 1Q5H; -.
DR PDBsum; 1Q5U; -.
DR PDBsum; 2HQU; -.
DR PDBsum; 3ARA; -.
DR PDBsum; 3ARN; -.
DR PDBsum; 3EHW; -.
DR PDBsum; 4MZ5; -.
DR PDBsum; 4MZ6; -.
DR PDBsum; 5H4J; -.
DR AlphaFoldDB; P33316; -.
DR BMRB; P33316; -.
DR SASBDB; P33316; -.
DR SMR; P33316; -.
DR BioGRID; 108187; 115.
DR IntAct; P33316; 35.
DR MINT; P33316; -.
DR STRING; 9606.ENSP00000370376; -.
DR BindingDB; P33316; -.
DR ChEMBL; CHEMBL5203; -.
DR DrugBank; DB04685; 1-{(2S,5S)-4-FLUORO-5-[(TRITYLOXY)METHYL]TETRAHYDROFURAN-2-YL}PYRIMIDINE-2,4(1H,3H)-DIONE.
DR DrugBank; DB03413; Deoxyuridine-5'-Diphosphate.
DR GlyGen; P33316; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P33316; -.
DR MetOSite; P33316; -.
DR PhosphoSitePlus; P33316; -.
DR SwissPalm; P33316; -.
DR BioMuta; DUT; -.
DR DMDM; 347595814; -.
DR CPTAC; CPTAC-64; -.
DR CPTAC; CPTAC-65; -.
DR EPD; P33316; -.
DR jPOST; P33316; -.
DR MassIVE; P33316; -.
DR MaxQB; P33316; -.
DR PaxDb; P33316; -.
DR PeptideAtlas; P33316; -.
DR PRIDE; P33316; -.
DR ProteomicsDB; 54908; -. [P33316-3]
DR ProteomicsDB; 54909; -. [P33316-2]
DR TopDownProteomics; P33316-2; -. [P33316-2]
DR TopDownProteomics; P33316-3; -. [P33316-3]
DR Antibodypedia; 24524; 384 antibodies from 31 providers.
DR DNASU; 1854; -.
DR Ensembl; ENST00000331200.8; ENSP00000370376.2; ENSG00000128951.14. [P33316-3]
DR Ensembl; ENST00000455976.6; ENSP00000405160.2; ENSG00000128951.14. [P33316-2]
DR GeneID; 1854; -.
DR KEGG; hsa:1854; -.
DR MANE-Select; ENST00000331200.8; ENSP00000370376.2; NM_001025248.2; NP_001020419.1.
DR UCSC; uc001zws.4; human. [P33316-3]
DR CTD; 1854; -.
DR DisGeNET; 1854; -.
DR GeneCards; DUT; -.
DR HGNC; HGNC:3078; DUT.
DR HPA; ENSG00000128951; Low tissue specificity.
DR MIM; 601266; gene.
DR neXtProt; NX_P33316; -.
DR OpenTargets; ENSG00000128951; -.
DR PharmGKB; PA151; -.
DR VEuPathDB; HostDB:ENSG00000128951; -.
DR eggNOG; KOG3370; Eukaryota.
DR GeneTree; ENSGT00390000018390; -.
DR OrthoDB; 1495752at2759; -.
DR PhylomeDB; P33316; -.
DR TreeFam; TF105416; -.
DR BioCyc; MetaCyc:HS05235-MON; -.
DR BRENDA; 3.6.1.23; 2681.
DR PathwayCommons; P33316; -.
DR Reactome; R-HSA-499943; Interconversion of nucleotide di- and triphosphates. [P33316-2]
DR SABIO-RK; P33316; -.
DR SignaLink; P33316; -.
DR SIGNOR; P33316; -.
DR UniPathway; UPA00610; UER00666.
DR BioGRID-ORCS; 1854; 801 hits in 1108 CRISPR screens.
DR ChiTaRS; DUT; human.
DR EvolutionaryTrace; P33316; -.
DR GeneWiki; DUT_(gene); -.
DR GenomeRNAi; 1854; -.
DR Pharos; P33316; Tchem.
DR PRO; PR:P33316; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P33316; protein.
DR Bgee; ENSG00000128951; Expressed in pylorus and 213 other tissues.
DR ExpressionAtlas; P33316; baseline and differential.
DR Genevisible; P33316; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; TAS:ProtInc.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0004170; F:dUTP diphosphatase activity; IDA:MGI.
DR GO; GO:0000287; F:magnesium ion binding; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0006260; P:DNA replication; TAS:ProtInc.
DR GO; GO:0006231; P:dTMP biosynthetic process; IDA:MGI.
DR GO; GO:0006226; P:dUMP biosynthetic process; IBA:GO_Central.
DR GO; GO:0046081; P:dUTP catabolic process; IBA:GO_Central.
DR GO; GO:0006139; P:nucleobase-containing compound metabolic process; TAS:ProtInc.
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 3D-structure; Alternative splicing; Direct protein sequencing; Hydrolase;
KW Magnesium; Mitochondrion; Nucleotide metabolism; Nucleus; Phosphoprotein;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..69
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:8631816,
FT ECO:0000269|PubMed:8631817, ECO:0007744|PubMed:25944712"
FT CHAIN 70..252
FT /note="Deoxyuridine 5'-triphosphate nucleotidohydrolase,
FT mitochondrial"
FT /id="PRO_0000007392"
FT REGION 78..104
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 173..175
FT /ligand="dUTP"
FT /ligand_id="ChEBI:CHEBI:61555"
FT /evidence="ECO:0000269|PubMed:8805593,
FT ECO:0000305|PubMed:17880943, ECO:0007744|PDB:1Q5H,
FT ECO:0007744|PDB:2HQU, ECO:0007744|PDB:3EHW"
FT BINDING 187..193
FT /ligand="dUTP"
FT /ligand_id="ChEBI:CHEBI:61555"
FT /evidence="ECO:0000269|PubMed:8805593,
FT ECO:0000305|PubMed:17880943, ECO:0007744|PDB:1Q5H,
FT ECO:0007744|PDB:2HQU, ECO:0007744|PDB:3ARA,
FT ECO:0007744|PDB:3ARN, ECO:0007744|PDB:3EHW"
FT BINDING 198
FT /ligand="dUTP"
FT /ligand_id="ChEBI:CHEBI:61555"
FT /evidence="ECO:0000269|PubMed:8805593,
FT ECO:0000305|PubMed:17880943, ECO:0007744|PDB:1Q5H,
FT ECO:0007744|PDB:2HQU, ECO:0007744|PDB:3ARA,
FT ECO:0007744|PDB:3ARN, ECO:0007744|PDB:3EHW"
FT BINDING 241
FT /ligand="dUTP"
FT /ligand_id="ChEBI:CHEBI:61555"
FT /evidence="ECO:0000269|PubMed:8805593,
FT ECO:0000305|PubMed:17880943, ECO:0007744|PDB:1Q5H,
FT ECO:0007744|PDB:2HQU, ECO:0007744|PDB:3EHW"
FT BINDING 246..247
FT /ligand="dUTP"
FT /ligand_id="ChEBI:CHEBI:61555"
FT /evidence="ECO:0000269|PubMed:8805593,
FT ECO:0000305|PubMed:17880943, ECO:0007744|PDB:1Q5H,
FT ECO:0007744|PDB:2HQU, ECO:0007744|PDB:3EHW"
FT MOD_RES 88
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 99
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..93
FT /note="MTPLCPRPALCYHFLTSLLRSAMQNARGARQRAEAAVLSGPGPPLGRAAQHG
FT IPRPLSSAGRLSQGCRGASTVGAAGWKGELPKAGGSPAPGP -> MPCSE (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:8631816,
FT ECO:0000303|PubMed:9070952, ECO:0000303|Ref.5,
FT ECO:0000303|Ref.7"
FT /id="VSP_001324"
FT VARIANT 100
FT /note="P -> S (in dbSNP:rs28381104)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_022314"
FT MUTAGEN 99
FT /note="S->A: Loss of phosphorylation."
FT /evidence="ECO:0000269|PubMed:8631817"
FT CONFLICT 175
FT /note="G -> S (in Ref. 6; BAF84204)"
FT /evidence="ECO:0000305"
FT CONFLICT 182
FT /note="I -> T (in Ref. 6; BAG60677)"
FT /evidence="ECO:0000305"
FT STRAND 113..120
FT /evidence="ECO:0007829|PDB:3ARA"
FT STRAND 127..130
FT /evidence="ECO:0007829|PDB:3EHW"
FT STRAND 134..139
FT /evidence="ECO:0007829|PDB:3ARA"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:3ARA"
FT STRAND 150..155
FT /evidence="ECO:0007829|PDB:3ARA"
FT STRAND 158..161
FT /evidence="ECO:0007829|PDB:3ARA"
FT STRAND 166..171
FT /evidence="ECO:0007829|PDB:3ARA"
FT HELIX 174..180
FT /evidence="ECO:0007829|PDB:3ARA"
FT STRAND 182..185
FT /evidence="ECO:0007829|PDB:3ARA"
FT STRAND 198..203
FT /evidence="ECO:0007829|PDB:3ARA"
FT STRAND 205..207
FT /evidence="ECO:0007829|PDB:3ARA"
FT STRAND 209..211
FT /evidence="ECO:0007829|PDB:3ARA"
FT STRAND 216..226
FT /evidence="ECO:0007829|PDB:3ARA"
FT STRAND 229..232
FT /evidence="ECO:0007829|PDB:3ARA"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:3EHW"
FT TURN 246..249
FT /evidence="ECO:0007829|PDB:3EHW"
FT INIT_MET P33316-2:1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:8631816"
FT MOD_RES P33316-2:11
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:8631817,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
SQ SEQUENCE 252 AA; 26563 MW; 8E2EBC9ED5B0FAD2 CRC64;
MTPLCPRPAL CYHFLTSLLR SAMQNARGAR QRAEAAVLSG PGPPLGRAAQ HGIPRPLSSA
GRLSQGCRGA STVGAAGWKG ELPKAGGSPA PGPETPAISP SKRARPAEVG GMQLRFARLS
EHATAPTRGS ARAAGYDLYS AYDYTIPPME KAVVKTDIQI ALPSGCYGRV APRSGLAAKH
FIDVGAGVID EDYRGNVGVV LFNFGKEKFE VKKGDRIAQL ICERIFYPEI EEVQALDDTE
RGSGGFGSTG KN
