WWOX_PONAB
ID WWOX_PONAB Reviewed; 414 AA.
AC Q5R9W5;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=WW domain-containing oxidoreductase;
DE EC=1.1.1.-;
GN Name=WWOX;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) 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, probably by sequestering DVL2 in
CC the cytoplasm (By similarity). {ECO:0000250|UniProtKB:Q9NZC7}.
CC -!- SUBUNIT: Interacts with TP53, p73/TP73 and MAPK8. Interacts with
CC MAPT/TAU, RUNX2 and HYAL2 (By similarity). Forms a ternary complex with
CC TP53 and MDM2. Interacts with ERBB4, LITAF and WBP1. Interacts with
CC DVL1, DVL2 and DVL3. May interact with FAM189B and SCOTIN (By
CC similarity). Interacts with TNK2 (By similarity). Interacts with
CC TMEM207 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9NZC7}. Nucleus
CC {ECO:0000250|UniProtKB:Q9NZC7}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q9NZC7}. Note=Partially localizes to the
CC mitochondria. Translocates to the nucleus upon genotoxic stress or TNF
CC stimulation (By similarity). Translocates to the nucleus in response to
CC TGFB1 (By similarity). {ECO:0000250|UniProtKB:Q9NZC7}.
CC -!- DOMAIN: The WW 1 domain mediates interaction with TP53, TP73, TFAP2C,
CC LITAF and WBP1. {ECO:0000250}.
CC -!- PTM: Phosphorylated upon genotoxic stress. Phosphorylation of Tyr-33
CC regulates interaction with TP53, TP73 and MAPK8. May also regulate
CC proapoptotic activity. Phosphorylation by TNK2 is associated with
CC polyubiquitination and degradation (By similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated when phosphorylated by TNK2, leading to its
CC degradation. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; CR859266; CAH91445.1; -; mRNA.
DR RefSeq; NP_001125849.1; NM_001132377.1.
DR AlphaFoldDB; Q5R9W5; -.
DR SMR; Q5R9W5; -.
DR STRING; 9601.ENSPPYP00000008550; -.
DR PRIDE; Q5R9W5; -.
DR GeneID; 100172779; -.
DR KEGG; pon:100172779; -.
DR CTD; 51741; -.
DR eggNOG; KOG1208; Eukaryota.
DR InParanoid; Q5R9W5; -.
DR OrthoDB; 1413827at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; 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:0030178; P:negative regulation of Wnt signaling pathway; ISS:UniProtKB.
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; 2.
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; 2.
DR PROSITE; PS50020; WW_DOMAIN_2; 2.
PE 2: Evidence at transcript level;
KW Apoptosis; Cytoplasm; Mitochondrion; NADP; Nucleus; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Repeat; Tumor suppressor;
KW Ubl conjugation; Wnt signaling pathway.
FT CHAIN 1..414
FT /note="WW domain-containing oxidoreductase"
FT /id="PRO_0000054817"
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 REGION 125..414
FT /note="Interaction with MAPT"
FT /evidence="ECO:0000250"
FT REGION 209..273
FT /note="Mediates targeting to the mitochondria"
FT /evidence="ECO:0000250"
FT MOTIF 50..55
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT ACT_SITE 293
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 131..137
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 260
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 12
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZC7"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZC7"
FT MOD_RES 33
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZC7"
FT MOD_RES 287
FT /note="Phosphotyrosine; by TNK2"
FT /evidence="ECO:0000250|UniProtKB:Q9NZC7"
SQ SEQUENCE 414 AA; 46513 MW; E7F22B2916735479 CRC64;
MAALRYAGLD DTDSEDELPP GWEERTTKDG WVYYANHTEE KTQWEHPKTG KRKRVAGDLP
YGWEQGTDEN GQVFFVDHIN KRTTYLDPRL AFTVDDNPTK PTTRQRYDGS TTALEILQGR
DFTGKVVVVT GANSGIGFET AKSFALHGAH VILACRNMAR ASEAVSRILE EWHKAKVEAV
TLDLALLRSV QHFAEAFKAK NVPLHVLVCN AATFALPWSL TKDGLETTFQ VNHLGHFYLV
QLLQDVLCRS APARVIVVSS ESHRFTDIND SLGKLDFSRL SPTKNDYWAM LAYNRSKLCN
VLFSNELHRR LSPRGVTSNA VHPGNMMYSN IHRSWWVYTL LFTLARPFTK SMQQGAATTV
YCAAAPELEG LGGMYFNNCC RCMPSPEAQS EETARTLWAL SERLIQERLG SQSG
