URIC_RAT
ID URIC_RAT Reviewed; 303 AA.
AC P09118;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Uricase;
DE EC=1.7.3.3 {ECO:0000269|PubMed:1520291};
DE AltName: Full=Urate oxidase;
GN Name=Uox;
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].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=2338140; DOI=10.1016/0014-5793(90)80789-l;
RA Motojima K., Goto S.;
RT "Organization of rat uricase chromosomal gene differs greatly from that of
RT the corresponding plant gene.";
RL FEBS Lett. 264:156-158(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=3182808; DOI=10.1016/s0021-9258(18)37443-x;
RA Motojima K., Kanaya S., Goto S.;
RT "Cloning and sequence analysis of cDNA for rat liver uricase.";
RL J. Biol. Chem. 263:16677-16681(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=2920046; DOI=10.1016/0006-291x(89)92820-9;
RA Alvares K., Nemali M.R., Reddy P.G., Wang X.D., Rao M.S., Reddy J.K.;
RT "The nucleotide sequence of a full length cDNA clone encoding rat liver
RT urate oxidase.";
RL Biochem. Biophys. Res. Commun. 158:991-995(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=3267221; DOI=10.1111/j.1432-1033.1988.tb14021.x;
RA Ito M., Suzuki M., Takagi Y.;
RT "Nucleotide sequence of cDNA and predicted amino acid sequence of rat liver
RT uricase.";
RL Eur. J. Biochem. 173:459-463(1988).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1999285; DOI=10.1016/0378-1119(91)90055-g;
RA Wang X.D., Kawano H., Alvares K., Reddy P.G., Getto H., Rao M.S.,
RA Reddy J.K.;
RT "Rat urate oxidase: cloning and structural analysis of the gene and 5'-
RT flanking region.";
RL Gene 97:223-229(1991).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1783398; DOI=10.1016/0888-7543(91)90013-5;
RA Ito M., Nakamura M., Ogawa H., Kato S., Takagi Y.;
RT "Structural analysis of the gene encoding rat uricase.";
RL Genomics 11:905-913(1991).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC 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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 11-303, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=3194410; DOI=10.1073/pnas.85.23.9081;
RA Reddy P.G., Nemali M.R., Reddy M.K., Reddy M.N., Yuan P.M., Yuen S.,
RA Laffler T.G., Shiroza T., Kuramitsu H.K., Usuda N., Chisholm R.L.,
RA Rao M.S., Reddy J.K.;
RT "Isolation and sequence determination of a cDNA clone for rat peroxisomal
RT urate oxidase: liver-specific expression in the rat.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:9081-9085(1988).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, PATHWAY, AND MUTAGENESIS OF LYS-164.
RX PubMed=1520291; DOI=10.1016/s0006-291x(05)81464-0;
RA Ito M., Kato S., Nakmura M., Go M., Takagi Y.;
RT "Identification of an amino acid residue involved in the substrate-binding
RT site of rat liver uricase by site-directed mutagenesis.";
RL Biochem. Biophys. Res. Commun. 187:101-107(1992).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-288, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Catalyzes the oxidation of uric acid to 5-hydroxyisourate,
CC which is further processed to form (S)-allantoin.
CC {ECO:0000269|PubMed:1520291}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O2 + urate = 5-hydroxyisourate + H2O2;
CC Xref=Rhea:RHEA:21368, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:17775, ChEBI:CHEBI:18072; EC=1.7.3.3;
CC Evidence={ECO:0000269|PubMed:1520291};
CC -!- ACTIVITY REGULATION: Competitively inhibited by xanthine.
CC {ECO:0000269|PubMed:1520291}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8.33 uM for urate {ECO:0000269|PubMed:1520291};
CC -!- PATHWAY: Purine metabolism; urate degradation; (S)-allantoin from
CC urate: step 1/3. {ECO:0000305|PubMed:1520291}.
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:3194410}.
CC -!- TISSUE SPECIFICITY: Expressed in liver. Not detected in other tissues
CC tested. {ECO:0000269|PubMed:3194410}.
CC -!- SIMILARITY: Belongs to the uricase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA42318.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA30378.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; J03959; AAA42318.1; ALT_FRAME; mRNA.
DR EMBL; X13098; CAA31490.1; -; mRNA.
DR EMBL; M24396; AAA42317.1; -; mRNA.
DR EMBL; X07497; CAA30378.1; ALT_FRAME; mRNA.
DR EMBL; M63593; AAA61699.1; -; Genomic_DNA.
DR EMBL; M63583; AAA61699.1; JOINED; Genomic_DNA.
DR EMBL; M63586; AAA61699.1; JOINED; Genomic_DNA.
DR EMBL; M63587; AAA61699.1; JOINED; Genomic_DNA.
DR EMBL; M63588; AAA61699.1; JOINED; Genomic_DNA.
DR EMBL; M63590; AAA61699.1; JOINED; Genomic_DNA.
DR EMBL; M63591; AAA61699.1; JOINED; Genomic_DNA.
DR EMBL; M63592; AAA61699.1; JOINED; Genomic_DNA.
DR EMBL; BC088112; AAH88112.1; -; mRNA.
DR PIR; I54070; RDRTU.
DR RefSeq; NP_446220.1; NM_053768.2.
DR AlphaFoldDB; P09118; -.
DR SMR; P09118; -.
DR STRING; 10116.ENSRNOP00000021970; -.
DR CarbonylDB; P09118; -.
DR iPTMnet; P09118; -.
DR PhosphoSitePlus; P09118; -.
DR PaxDb; P09118; -.
DR PRIDE; P09118; -.
DR GeneID; 114768; -.
DR KEGG; rno:114768; -.
DR CTD; 391051; -.
DR RGD; 621369; Uox.
DR VEuPathDB; HostDB:ENSRNOG00000016339; -.
DR eggNOG; KOG1599; Eukaryota.
DR HOGENOM; CLU_048151_1_0_1; -.
DR InParanoid; P09118; -.
DR OMA; THRWTRM; -.
DR OrthoDB; 906540at2759; -.
DR PhylomeDB; P09118; -.
DR TreeFam; TF323438; -.
DR UniPathway; UPA00394; UER00650.
DR PRO; PR:P09118; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000016339; Expressed in liver and 13 other tissues.
DR Genevisible; P09118; RN.
DR GO; GO:0005782; C:peroxisomal matrix; TAS:RGD.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0004846; F:urate oxidase activity; IDA:UniProtKB.
DR GO; GO:0006154; P:adenosine catabolic process; IEA:Ensembl.
DR GO; GO:0000255; P:allantoin metabolic process; IEA:Ensembl.
DR GO; GO:0006196; P:AMP catabolic process; IEA:Ensembl.
DR GO; GO:0046059; P:dAMP catabolic process; IEA:Ensembl.
DR GO; GO:0006157; P:deoxyadenosine catabolic process; IEA:Ensembl.
DR GO; GO:0006161; P:deoxyguanosine catabolic process; IEA:Ensembl.
DR GO; GO:0006149; P:deoxyinosine catabolic process; IEA:Ensembl.
DR GO; GO:0046055; P:dGMP catabolic process; IEA:Ensembl.
DR GO; GO:0046038; P:GMP catabolic process; IEA:Ensembl.
DR GO; GO:0006147; P:guanine catabolic process; IEA:Ensembl.
DR GO; GO:0009114; P:hypoxanthine catabolic process; IEA:Ensembl.
DR GO; GO:0006204; P:IMP catabolic process; IEA:Ensembl.
DR GO; GO:0006148; P:inosine catabolic process; IEA:Ensembl.
DR GO; GO:0006145; P:purine nucleobase catabolic process; IBA:GO_Central.
DR GO; GO:0019628; P:urate catabolic process; IDA:UniProtKB.
DR GO; GO:0009115; P:xanthine catabolic process; IEA:Ensembl.
DR InterPro; IPR002042; Uricase.
DR InterPro; IPR019842; Uricase_CS.
DR PANTHER; PTHR42874; PTHR42874; 1.
DR Pfam; PF01014; Uricase; 2.
DR PIRSF; PIRSF000241; Urate_oxidase; 1.
DR PRINTS; PR00093; URICASE.
DR TIGRFAMs; TIGR03383; urate_oxi; 1.
DR PROSITE; PS00366; URICASE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Direct protein sequencing; Oxidoreductase; Peroxisome;
KW Phosphoprotein; Purine metabolism; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P25688"
FT CHAIN 2..303
FT /note="Uricase"
FT /id="PRO_0000165990"
FT MOTIF 301..303
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 23
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:D0VWQ1"
FT ACT_SITE 68
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:D0VWQ1"
FT ACT_SITE 263
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:D0VWQ1"
FT BINDING 68..69
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:D0VWQ1"
FT BINDING 170
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:D0VWQ1"
FT BINDING 187
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:D0VWQ1"
FT BINDING 234..235
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:D0VWQ1"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P25688"
FT MOD_RES 10
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P25688"
FT MOD_RES 10
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P25688"
FT MOD_RES 23
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P25688"
FT MOD_RES 23
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P25688"
FT MOD_RES 27
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P25688"
FT MOD_RES 36
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P25688"
FT MOD_RES 39
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P25688"
FT MOD_RES 63
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P25688"
FT MOD_RES 118
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P25688"
FT MOD_RES 122
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P25688"
FT MOD_RES 164
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P25688"
FT MOD_RES 175
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P25688"
FT MOD_RES 185
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P25688"
FT MOD_RES 220
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P25688"
FT MOD_RES 220
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P25688"
FT MOD_RES 231
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P25688"
FT MOD_RES 277
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P25688"
FT MOD_RES 288
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MUTAGEN 164
FT /note="K->E,I: Loss of activity."
FT /evidence="ECO:0000269|PubMed:1520291"
FT CONFLICT 55
FT /note="K -> D (in Ref. 6)"
FT /evidence="ECO:0000305"
FT CONFLICT 111
FT /note="Y -> H (in Ref. 3; AAA42317 and 6)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 303 AA; 34934 MW; 14CFF2F4E18C7BBB CRC64;
MAHYHDDYGK NDEVEFVRTG YGKDMVKVLH IQRDGKYHSI KEVATSVQLT LRSKKDYLHG
DNSDIIPTDT IKNTVHVLAK FKGIKSIETF AMNICEHFLS SFSHVTRAHV YVEEVPWKRF
EKNGVKHVHA FIHTPTGTHF CDVEQVRNGP PIIHSGIKDL KVLKTTQSGF EGFIKDQFTT
LPEVKDRCFA TQVYCKWRYQ NRDVDFEATW GAVRDIVLKK FAGPYDRGEY SPSVQKTLYD
IQVLTLSQLP EIEDMEISLP NIHYFNIDMS KMGLINKEEV LLPLDNPYGK ITGTVRRKLP
SRL
