DUT_RAT
ID DUT_RAT Reviewed; 205 AA.
AC P70583;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2001, sequence version 3.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Deoxyuridine 5'-triphosphate nucleotidohydrolase;
DE Short=dUTPase;
DE EC=3.6.1.23 {ECO:0000250|UniProtKB:P33316};
DE AltName: Full=PPAR-interacting protein 4;
DE Short=PIP4;
DE AltName: Full=dUTP pyrophosphatase;
GN Name=Dut; Synonyms=Dutp;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND FUNCTION.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=8910358; DOI=10.1074/jbc.271.44.27670;
RA Chu R.Y., Lin Y.L., Rao M.S., Reddy J.K.;
RT "Cloning and identification of rat deoxyuridine triphosphatase as an
RT inhibitor of peroxisome proliferator-activated receptor alpha.";
RL J. Biol. Chem. 271:27670-27676(1996).
RN [2]
RP SEQUENCE REVISION.
RA Chu R.Y., Lin Y.L., Rao M.S., Reddy J.K.;
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
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 (PubMed:8910358). Essential for embryonic
CC development (By similarity). {ECO:0000250|UniProtKB:P33316,
CC ECO:0000250|UniProtKB:Q9CQ43, ECO:0000269|PubMed:8910358}.
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: Cytoplasm {ECO:0000269|PubMed:8910358}. Nucleus
CC {ECO:0000269|PubMed:8910358}. Note=Binding to PPAR induces
CC translocation to the nucleus. {ECO:0000269|PubMed:8910358}.
CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined. Higher levels in
CC heart and kidney.
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 -!- SIMILARITY: Belongs to the dUTPase family. {ECO:0000305}.
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DR EMBL; U64030; AAC34734.2; -; mRNA.
DR PIR; T10819; T10819.
DR RefSeq; NP_001035361.1; NM_001040271.1.
DR RefSeq; NP_446044.1; NM_053592.2.
DR AlphaFoldDB; P70583; -.
DR SMR; P70583; -.
DR BioGRID; 269088; 4.
DR STRING; 10116.ENSRNOP00000009549; -.
DR iPTMnet; P70583; -.
DR PhosphoSitePlus; P70583; -.
DR jPOST; P70583; -.
DR PaxDb; P70583; -.
DR PRIDE; P70583; -.
DR Ensembl; ENSRNOT00000009549; ENSRNOP00000009549; ENSRNOG00000007221.
DR GeneID; 497778; -.
DR KEGG; rno:497778; -.
DR UCSC; RGD:620849; rat.
DR CTD; 1854; -.
DR RGD; 620849; Dut.
DR eggNOG; KOG3370; Eukaryota.
DR GeneTree; ENSGT00390000018390; -.
DR HOGENOM; CLU_068508_2_0_1; -.
DR InParanoid; P70583; -.
DR OMA; YAAFVHP; -.
DR OrthoDB; 1495752at2759; -.
DR PhylomeDB; P70583; -.
DR TreeFam; TF105416; -.
DR Reactome; R-RNO-499943; Interconversion of nucleotide di- and triphosphates.
DR UniPathway; UPA00610; UER00666.
DR PRO; PR:P70583; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000007221; Expressed in thymus and 19 other tissues.
DR Genevisible; P70583; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0004170; F:dUTP diphosphatase activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0000287; F:magnesium ion binding; IBA:GO_Central.
DR GO; GO:0042975; F:peroxisome proliferator activated receptor binding; IPI:RGD.
DR GO; GO:0032556; F:pyrimidine deoxyribonucleotide binding; IDA:RGD.
DR GO; GO:0030547; F:signaling receptor inhibitor activity; IDA:RGD.
DR GO; GO:0006231; P:dTMP biosynthetic process; ISO:RGD.
DR GO; GO:0006226; P:dUMP biosynthetic process; IDA:RGD.
DR GO; GO:0046081; P:dUTP catabolic process; IDA:RGD.
DR GO; GO:0001889; P:liver development; IEP:RGD.
DR GO; GO:0043254; P:regulation of protein-containing complex assembly; IDA:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
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 2: Evidence at transcript level;
KW Cytoplasm; Hydrolase; Magnesium; Metal-binding; Nucleotide metabolism;
KW Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..205
FT /note="Deoxyuridine 5'-triphosphate nucleotidohydrolase"
FT /id="PRO_0000182926"
FT BINDING 126..128
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P33316"
FT BINDING 140..143
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P33316"
FT BINDING 151
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P33316"
FT BINDING 199..200
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P33316"
FT MOD_RES 54
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P33316"
SQ SEQUENCE 205 AA; 22003 MW; A9D54EBF5ED015C4 CRC64;
MPLLCALLRS RLQPSLLRSL TLTSAQSLSC GGSRGVRTWS ARTGPGACAD PAVSVSKRAR
AEDDASLRFV RLSEHATAPT RGSARAAGYD LYSAYDYTIP SMEKALVKTD IQIAVPSGCY
GRVAPRSGLA VKHFIDVGAG VIDEDYRGNV GVVLFNFGKE KFEVKKGDRI AQLICERILY
PDLEEVQTLD NTERGSGGFG STGKN
