ID   WWOX_DANRE              Reviewed;         412 AA.
AC   Q803A8;
DT   22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2003, sequence version 1.
DT   03-AUG-2022, entry version 115.
DE   RecName: Full=WW domain-containing oxidoreductase;
DE            EC=1.1.1.-;
GN   Name=wwox;
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 [LARGE SCALE MRNA].
RC   STRAIN=AB;
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Putative oxidoreductase. Acts as a tumor suppressor and plays
CC       a role in apoptosis. May function synergistically with p53/TP53 to
CC       control genotoxic stress-induced cell death. Plays a role in TGFB1
CC       signaling and TGFB1-mediated cell death. May also play a role in tumor
CC       necrosis factor (TNF)-mediated cell death. Required for normal bone
CC       development. Inhibits Wnt signaling (By similarity).
CC       {ECO:0000250|UniProtKB:Q9NZC7}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9NZC7}. Nucleus
CC       {ECO:0000250|UniProtKB:Q9NZC7}.
CC   -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC       family. {ECO:0000305}.
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DR   EMBL; BC044560; AAH44560.1; -; mRNA.
DR   RefSeq; NP_957207.1; NM_200913.1.
DR   AlphaFoldDB; Q803A8; -.
DR   SMR; Q803A8; -.
DR   STRING; 7955.ENSDARP00000020652; -.
DR   iPTMnet; Q803A8; -.
DR   PaxDb; Q803A8; -.
DR   GeneID; 393887; -.
DR   KEGG; dre:393887; -.
DR   CTD; 51741; -.
DR   ZFIN; ZDB-GENE-040426-858; wwox.
DR   eggNOG; KOG1208; Eukaryota.
DR   InParanoid; Q803A8; -.
DR   OrthoDB; 1413827at2759; -.
DR   PhylomeDB; Q803A8; -.
DR   Reactome; R-DRE-1251985; Nuclear signaling by ERBB4.
DR   Reactome; R-DRE-8866904; Negative regulation of activity of TFAP2 (AP-2) family transcription factors.
DR   Reactome; R-DRE-8866907; Activation of the TFAP2 (AP-2) family of transcription factors.
DR   PRO; PR:Q803A8; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0006874; P:cellular calcium ion homeostasis; IMP:ZFIN.
DR   GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR   CDD; cd09809; human_WWOX_like_SDR_c-like; 1.
DR   CDD; cd00201; WW; 2.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR002347; SDR_fam.
DR   InterPro; IPR001202; WW_dom.
DR   InterPro; IPR036020; WW_dom_sf.
DR   InterPro; IPR042732; WWOX_SDR_c-like.
DR   Pfam; PF00106; adh_short; 1.
DR   Pfam; PF00397; WW; 1.
DR   PRINTS; PR00081; GDHRDH.
DR   SMART; SM00456; WW; 2.
DR   SUPFAM; SSF51045; SSF51045; 2.
DR   SUPFAM; SSF51735; SSF51735; 1.
DR   PROSITE; PS01159; WW_DOMAIN_1; 1.
DR   PROSITE; PS50020; WW_DOMAIN_2; 2.
PE   2: Evidence at transcript level;
KW   Apoptosis; Cytoplasm; NADP; Nucleus; Oxidoreductase; Phosphoprotein;
KW   Reference proteome; Repeat; Wnt signaling pathway.
FT   CHAIN           1..412
FT                   /note="WW domain-containing oxidoreductase"
FT                   /id="PRO_0000054819"
FT   DOMAIN          16..49
FT                   /note="WW 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT   DOMAIN          57..90
FT                   /note="WW 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT   REGION          1..24
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           50..55
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        290
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         128..134
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         257
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   412 AA;  46322 MW;  D4D10CA809138B8D CRC64;
     MAALKYAGME DTDSEDELPP GWEERSTKDG WVYYANHEEM KTQWEHPKTG KKKRCAGALP
     YGWEQETDDK GQIFYVDHIN KRKTYFDPRQ AFTVEDMQVK PKRYDGNTGA LEILHGQDLS
     DKVIIVTGAN SGIGFETARS FALHGAHVIL ACRNQSRASK AASLIMGEWS KARVEVLPLD
     LASLRSVRQF AELFKATKLP LHVLVCNAAV CSQPWRLTED GFESTFQICH LGHFLLVQLL
     QDVLRLSAPA RVVVVSSESH RFTDLLDSCG NLDLDLLSPP QKNYWSLLAY NRAKLCNLLF
     SSELHRRMSP HGICCNALHP GSMMFTSIHR SWWLLTLLFS LARPFTKSMQ QGAATTVYCA
     VAPELEGIGG MYFNNCFRCL PSPQAQDPAA ALSLWELSER LVQERSTPPQ VL