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HIUH_DANRE
ID   HIUH_DANRE              Reviewed;         138 AA.
AC   Q06S87; Q0P422;
DT   15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT   31-OCT-2006, sequence version 1.
DT   03-AUG-2022, entry version 99.
DE   RecName: Full=5-hydroxyisourate hydrolase;
DE            Short=HIU hydrolase;
DE            Short=HIUHase;
DE            EC=3.5.2.17;
DE   AltName: Full=Transthyretin-related protein;
GN   Name=urah;
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;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), X-RAY CRYSTALLOGRAPHY (1.7
RP   ANGSTROMS) OF 20-138, CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-69, AND
RP   SUBUNIT.
RX   PubMed=16952372; DOI=10.1016/j.jmb.2006.07.079;
RA   Zanotti G., Cendron L., Ramazzina I., Folli C., Percudani R., Berni R.;
RT   "Structure of zebra fish HIUase: insights into evolution of an enzyme to a
RT   hormone transporter.";
RL   J. Mol. Biol. 363:1-9(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 44-138 (ISOFORM 2).
RC   TISSUE=Liver;
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Catalyzes the hydrolysis of 5-hydroxyisourate (HIU) to 2-oxo-
CC       4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU).
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=5-hydroxyisourate + H2O = 5-hydroxy-2-oxo-4-ureido-2,5-
CC         dihydro-1H-imidazole-5-carboxylate + H(+); Xref=Rhea:RHEA:23736,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:18072,
CC         ChEBI:CHEBI:58639; EC=3.5.2.17;
CC         Evidence={ECO:0000269|PubMed:16952372};
CC   -!- PATHWAY: Purine metabolism; urate degradation; (S)-allantoin from
CC       urate: step 2/3.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q06S87-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q06S87-2; Sequence=VSP_030524;
CC   -!- MISCELLANEOUS: HIU hydrolysis also occurs spontaneously, but more
CC       slowly.
CC   -!- SIMILARITY: Belongs to the transthyretin family. 5-hydroxyisourate
CC       hydrolase subfamily. {ECO:0000305}.
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DR   EMBL; DQ640307; ABG21128.1; -; mRNA.
DR   EMBL; BC122322; AAI22323.1; -; mRNA.
DR   RefSeq; XP_009291914.1; XM_009293639.2.
DR   PDB; 2H1X; X-ray; 1.98 A; A/B/C/D=22-138.
DR   PDB; 2H6U; X-ray; 1.70 A; A/B/C/D/E/F/G/H=22-138.
DR   PDB; 3IWU; X-ray; 2.30 A; A/B/C/D/E/F/G/H=1-138.
DR   PDB; 3IWV; X-ray; 1.68 A; A/B/C/D=1-138.
DR   PDB; 3Q1E; X-ray; 1.95 A; A/B/C/D=20-138.
DR   PDBsum; 2H1X; -.
DR   PDBsum; 2H6U; -.
DR   PDBsum; 3IWU; -.
DR   PDBsum; 3IWV; -.
DR   PDBsum; 3Q1E; -.
DR   AlphaFoldDB; Q06S87; -.
DR   SMR; Q06S87; -.
DR   STRING; 7955.ENSDARP00000090143; -.
DR   PaxDb; Q06S87; -.
DR   Ensembl; ENSDART00000163471; ENSDARP00000138143; ENSDARG00000100719. [Q06S87-2]
DR   ZFIN; ZDB-GENE-060825-253; uraha.
DR   eggNOG; KOG3006; Eukaryota.
DR   GeneTree; ENSGT00940000153229; -.
DR   InParanoid; Q06S87; -.
DR   OMA; ENQNYHI; -.
DR   PhylomeDB; Q06S87; -.
DR   BRENDA; 3.5.2.17; 928.
DR   UniPathway; UPA00394; UER00651.
DR   EvolutionaryTrace; Q06S87; -.
DR   PRO; PR:Q06S87; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Chromosome 18.
DR   Bgee; ENSDARG00000100719; Expressed in liver and 16 other tissues.
DR   ExpressionAtlas; Q06S87; baseline and differential.
DR   GO; GO:0005777; C:peroxisome; NAS:ZFIN.
DR   GO; GO:0016811; F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides; IDA:ZFIN.
DR   GO; GO:0033971; F:hydroxyisourate hydrolase activity; IDA:ZFIN.
DR   GO; GO:0006144; P:purine nucleobase metabolic process; IDA:ZFIN.
DR   GO; GO:0019628; P:urate catabolic process; IEA:UniProtKB-UniPathway.
DR   Gene3D; 2.60.40.180; -; 1.
DR   InterPro; IPR014306; Hydroxyisourate_hydrolase.
DR   InterPro; IPR023418; Thyroxine_BS.
DR   InterPro; IPR000895; Transthyretin/HIU_hydrolase.
DR   InterPro; IPR023416; Transthyretin/HIU_hydrolase_d.
DR   InterPro; IPR036817; Transthyretin/HIU_hydrolase_sf.
DR   PANTHER; PTHR10395; PTHR10395; 1.
DR   Pfam; PF00576; Transthyretin; 1.
DR   PRINTS; PR00189; TRNSTHYRETIN.
DR   SMART; SM00095; TR_THY; 1.
DR   SUPFAM; SSF49472; SSF49472; 1.
DR   TIGRFAMs; TIGR02962; hdxy_isourate; 1.
DR   PROSITE; PS00768; TRANSTHYRETIN_1; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Hydrolase; Peroxisome;
KW   Purine metabolism; Reference proteome.
FT   CHAIN           1..138
FT                   /note="5-hydroxyisourate hydrolase"
FT                   /id="PRO_0000315283"
FT   BINDING         31
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         71
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         135
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         1..43
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_030524"
FT   MUTAGEN         69
FT                   /note="D->A: Reduces activity by 50%."
FT                   /evidence="ECO:0000269|PubMed:16952372"
FT   STRAND          27..29
FT                   /evidence="ECO:0007829|PDB:2H6U"
FT   STRAND          32..34
FT                   /evidence="ECO:0007829|PDB:3IWV"
FT   TURN            35..38
FT                   /evidence="ECO:0007829|PDB:3IWV"
FT   STRAND          45..51
FT                   /evidence="ECO:0007829|PDB:3IWV"
FT   STRAND          53..55
FT                   /evidence="ECO:0007829|PDB:3IWV"
FT   STRAND          58..65
FT                   /evidence="ECO:0007829|PDB:3IWV"
FT   TURN            78..80
FT                   /evidence="ECO:0007829|PDB:3IWV"
FT   STRAND          83..90
FT                   /evidence="ECO:0007829|PDB:3IWV"
FT   HELIX           92..98
FT                   /evidence="ECO:0007829|PDB:3IWV"
FT   STRAND          108..114
FT                   /evidence="ECO:0007829|PDB:3IWV"
FT   STRAND          125..128
FT                   /evidence="ECO:0007829|PDB:3IWV"
FT   STRAND          131..135
FT                   /evidence="ECO:0007829|PDB:3IWV"
SQ   SEQUENCE   138 AA;  15486 MW;  BC8EEBCFF5116862 CRC64;
     MNRLQHIRGH IVSADKHINM SATLLSPLST HVLNIAQGVP GANMTIVLHR LDPVSSAWNI
     LTTGITNDDG RCPGLITKEN FIAGVYKMRF ETGKYWDALG ETCFYPYVEI VFTITNTSQH
     YHVPLLLSRF SYSTYRGS
 
 
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