URIC_DANRE
ID URIC_DANRE Reviewed; 298 AA.
AC Q6DG85;
DT 07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Uricase {ECO:0000255|PIRNR:PIRNR000241, ECO:0000255|RuleBase:RU004455, ECO:0000305};
DE EC=1.7.3.3 {ECO:0000255|PIRNR:PIRNR000241, ECO:0000255|RuleBase:RU004455, ECO:0000269|PubMed:27922051};
DE AltName: Full=Urate oxidase {ECO:0000255|PIRNR:PIRNR000241, ECO:0000303|PubMed:27922051};
GN Name=uox {ECO:0000312|ZFIN:ZDB-GENE-030826-24};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000312|EMBL:AAH76466.1};
RN [1] {ECO:0000312|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2] {ECO:0000312|EMBL:AAH76466.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0007744|PDB:5M98}
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, SUBUNIT, AND
RP MUTAGENESIS OF PHE-216.
RX PubMed=27922051; DOI=10.1038/srep38302;
RA Marchetti M., Liuzzi A., Fermi B., Corsini R., Folli C., Speranzini V.,
RA Gandolfi F., Bettati S., Ronda L., Cendron L., Berni R., Zanotti G.,
RA Percudani R.;
RT "Catalysis and structure of zebrafish urate oxidase provide insights into
RT the origin of hyperuricemia in hominoids.";
RL Sci. Rep. 6:38302-38302(2016).
CC -!- FUNCTION: Catalyzes the oxidation of uric acid to 5-hydroxyisourate,
CC which is further processed to form (S)-allantoin.
CC {ECO:0000255|PIRNR:PIRNR000241, ECO:0000255|RuleBase:RU004455,
CC ECO:0000269|PubMed:27922051}.
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:0000255|PIRNR:PIRNR000241,
CC ECO:0000255|RuleBase:RU004455, ECO:0000269|PubMed:27922051};
CC -!- ACTIVITY REGULATION: Competitively inhibited by xanthine.
CC {ECO:0000269|PubMed:27922051}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=11 uM for urate {ECO:0000269|PubMed:27922051};
CC -!- PATHWAY: Purine metabolism; urate degradation; (S)-allantoin from
CC urate: step 1/3. {ECO:0000255|PIRNR:PIRNR000241,
CC ECO:0000269|PubMed:27922051}.
CC -!- SUBUNIT: Homotetramer; dimer of dimers. {ECO:0000269|PubMed:27922051}.
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000250|UniProtKB:P09118,
CC ECO:0000255|PIRNR:PIRNR000241}.
CC -!- SIMILARITY: Belongs to the uricase family.
CC {ECO:0000255|PIRNR:PIRNR000241, ECO:0000255|RuleBase:RU004455,
CC ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CR931978; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC076466; AAH76466.1; -; mRNA.
DR EMBL; BC164061; AAI64061.1; -; mRNA.
DR RefSeq; NP_001002332.1; NM_001002332.1.
DR PDB; 5LL1; X-ray; 2.80 A; A/B/C/D/E/F/G/H=1-298.
DR PDB; 5M98; X-ray; 2.80 A; A/B/C/D/E/F/G/H=1-298.
DR PDBsum; 5LL1; -.
DR PDBsum; 5M98; -.
DR AlphaFoldDB; Q6DG85; -.
DR SMR; Q6DG85; -.
DR STRING; 7955.ENSDARP00000026870; -.
DR Ensembl; ENSDART00000146940; ENSDARP00000121053; ENSDARG00000007024.
DR GeneID; 436604; -.
DR KEGG; dre:436604; -.
DR CTD; 391051; -.
DR ZFIN; ZDB-GENE-030826-24; uox.
DR eggNOG; KOG1599; Eukaryota.
DR GeneTree; ENSGT00940000153229; -.
DR OrthoDB; 906540at2759; -.
DR PhylomeDB; Q6DG85; -.
DR TreeFam; TF323438; -.
DR UniPathway; UPA00394; UER00650.
DR PRO; PR:Q6DG85; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 11.
DR Bgee; ENSDARG00000007024; Expressed in liver and 20 other tissues.
DR ExpressionAtlas; Q6DG85; baseline and differential.
DR GO; GO:0005777; C:peroxisome; IBA:GO_Central.
DR GO; GO:0004846; F:urate oxidase activity; IDA:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IPI:ZFIN.
DR GO; GO:0006145; P:purine nucleobase catabolic process; IBA:GO_Central.
DR GO; GO:0019628; P:urate catabolic process; IDA:UniProtKB.
DR InterPro; IPR002042; Uricase.
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.
PE 1: Evidence at protein level;
KW 3D-structure; Oxidoreductase; Peroxisome; Purine metabolism;
KW Reference proteome.
FT CHAIN 1..298
FT /note="Uricase"
FT /id="PRO_0000440161"
FT MOTIF 296..298
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 18
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:D0VWQ1"
FT ACT_SITE 63
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:D0VWQ1"
FT ACT_SITE 258
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:D0VWQ1"
FT BINDING 63..64
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:D0VWQ1"
FT BINDING 165
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:D0VWQ1"
FT BINDING 182
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:D0VWQ1"
FT BINDING 229..230
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:D0VWQ1"
FT MUTAGEN 216
FT /note="F->S: Impairs catalytic activity. Has reduced
FT affinity for substrate."
FT /evidence="ECO:0000269|PubMed:27922051"
FT STRAND 9..28
FT /evidence="ECO:0007829|PDB:5LL1"
FT STRAND 33..47
FT /evidence="ECO:0007829|PDB:5LL1"
FT HELIX 50..54
FT /evidence="ECO:0007829|PDB:5LL1"
FT HELIX 63..77
FT /evidence="ECO:0007829|PDB:5LL1"
FT HELIX 82..95
FT /evidence="ECO:0007829|PDB:5LL1"
FT STRAND 98..109
FT /evidence="ECO:0007829|PDB:5LL1"
FT STRAND 112..117
FT /evidence="ECO:0007829|PDB:5LL1"
FT STRAND 120..128
FT /evidence="ECO:0007829|PDB:5LL1"
FT STRAND 131..141
FT /evidence="ECO:0007829|PDB:5LL1"
FT STRAND 147..163
FT /evidence="ECO:0007829|PDB:5LL1"
FT STRAND 179..181
FT /evidence="ECO:0007829|PDB:5LL1"
FT STRAND 184..195
FT /evidence="ECO:0007829|PDB:5LL1"
FT HELIX 201..217
FT /evidence="ECO:0007829|PDB:5LL1"
FT TURN 220..222
FT /evidence="ECO:0007829|PDB:5LL1"
FT HELIX 229..243
FT /evidence="ECO:0007829|PDB:5LL1"
FT STRAND 247..257
FT /evidence="ECO:0007829|PDB:5LL1"
FT STRAND 259..261
FT /evidence="ECO:0007829|PDB:5LL1"
FT HELIX 265..267
FT /evidence="ECO:0007829|PDB:5LL1"
FT STRAND 272..278
FT /evidence="ECO:0007829|PDB:5LL1"
FT STRAND 281..292
FT /evidence="ECO:0007829|PDB:5LL1"
SQ SEQUENCE 298 AA; 34187 MW; 70DF394B24EF0DF1 CRC64;
MATTSNQNVE FVRTGYGKNM VKVLHIRREG NHHHIIELIA NVQLTLKTRK DYLTGDNSDI
IPTDTVKNTV HALAKLKGIK SIESFALDIC EHFLTAFNHV TRVKVNIDEV PWKRLEKNGV
EHNHAFIHCP EALRFCEAEQ YLSKTPVVHS GLKDMKVLKT TQTGFEGFLR DRFTTLTDAK
DRFFCTSVYA RWRYNTINVA FDAAWKAVKD TVIQKFAGPY DRGEYSPSVQ KTLYDTQLLV
LDRIPEVEEI EIIMPNQHYF VIDMTKIGLS NKDEVYLPLD NPSGNITGTV CRKPRARM
