UniProtKB - Q91WL8 (WWOX_MOUSE)
Protein
WW domain-containing oxidoreductase
Gene
Wwox
Organism
Mus musculus (Mouse)
Status
Functioni
Putative oxidoreductase. Acts as a tumor suppressor and plays a role in apoptosis. May function synergistically with p53/TP53 to control genotoxic stress-induced cell death. Plays a role in TGFB1 signaling and TGFB1-mediated cell death. Inhibits Wnt signaling, probably by sequestering DVL2 in the cytoplasm (By similarity). May also play a role in tumor necrosis factor (TNF)-mediated cell death. Required for normal bone development.By similarity2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 260 | SubstrateBy similarity | 1 | |
Active sitei | 293 | Proton acceptorBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 131 – 137 | NADPBy similarity | 7 |
GO - Molecular functioni
- enzyme binding Source: BHF-UCL
- identical protein binding Source: MGI
- oxidoreductase activity Source: UniProtKB-KW
GO - Biological processi
- cellular response to transforming growth factor beta stimulus Source: BHF-UCL
- extrinsic apoptotic signaling pathway Source: MGI
- intrinsic apoptotic signaling pathway by p53 class mediator Source: MGI
- negative regulation of Wnt signaling pathway Source: UniProtKB
- osteoblast differentiation Source: MGI
- positive regulation of extrinsic apoptotic signaling pathway Source: BHF-UCL
- positive regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: MGI
- positive regulation of transcription by RNA polymerase II Source: BHF-UCL
- skeletal system morphogenesis Source: MGI
- Wnt signaling pathway Source: UniProtKB-KW
Keywordsi
Molecular function | Oxidoreductase |
Biological process | Apoptosis, Wnt signaling pathway |
Ligand | NADP |
Enzyme and pathway databases
Reactomei | R-MMU-1251985, Nuclear signaling by ERBB4 R-MMU-8866904, Negative regulation of activity of TFAP2 (AP-2) family transcription factors R-MMU-8866907, Activation of the TFAP2 (AP-2) family of transcription factors |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:Wwox Synonyms:Wox1 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1931237, Wwox |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Mitochondrion
- Mitochondrion 1 Publication
Nucleus
- Nucleus 2 Publications
Note: Partially localizes to the mitochondria (By similarity). Translocates to the nucleus in response to TGFB1 (PubMed:19366691). Translocates to the nucleus upon genotoxic stress or TNF stimulation (PubMed:11058590).By similarity2 Publications
Cytosol
- cytosol Source: MGI
Golgi apparatus
- Golgi apparatus Source: MGI
Mitochondrion
- mitochondrion Source: MGI
Nucleus
- nucleoplasm Source: MGI
- nucleus Source: BHF-UCL
- RNA polymerase II transcription regulator complex Source: BHF-UCL
Plasma Membrane
- plasma membrane Source: Ensembl
Other locations
- cytoplasm Source: UniProtKB
- microvillus Source: Ensembl
Keywords - Cellular componenti
Cytoplasm, Mitochondrion, NucleusPathology & Biotechi
Disruption phenotypei
Indistinguishable from wild-type at birth, but die after three weeks due to metabolic syndrome characterized by serum hypoproteinemia, hypoalbuminemia, hypoglycemia, hypocalcemia, hypotriglyceridemia and hypocholesterolemia, growth retardation, decreased bone formation and increased bone resorption. In addition, spontaneous tumor development was observed.2 Publications
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 51 – 54 | KRKR → QGTG: Abolishes the TNF-induced nuclear translocation. 1 Publication | 4 |
Keywords - Diseasei
Tumor suppressorPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000054816 | 1 – 414 | WW domain-containing oxidoreductaseAdd BLAST | 414 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 12 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 14 | PhosphoserineCombined sources | 1 | |
Modified residuei | 33 | Phosphotyrosine1 Publication | 1 | |
Modified residuei | 287 | Phosphotyrosine; by TNK2By similarity | 1 |
Post-translational modificationi
Phosphorylated upon genotoxic stress. Phosphorylation of Tyr-33 regulates interaction with TP53, TP73 and MAPK8. May also regulate proapoptotic activity. Phosphorylation by TNK2 is associated with polyubiquitination and degradation (By similarity).By similarity
Ubiquitinated when phosphorylated by TNK2, leading to its degradation.By similarity
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q91WL8 |
PaxDbi | Q91WL8 |
PeptideAtlasi | Q91WL8 |
PRIDEi | Q91WL8 |
ProteomicsDBi | 299997 [Q91WL8-1] 299998 [Q91WL8-2] 299999 [Q91WL8-3] 300000 [Q91WL8-4] |
PTM databases
iPTMneti | Q91WL8 |
PhosphoSitePlusi | Q91WL8 |
SwissPalmi | Q91WL8 |
Expressioni
Tissue specificityi
Ubiquitous. In the brain, expressed in cortex, striatum, hippocampus and cerebellum (at protein level). Detected in embryonic skeleton, in cranofacial bones, vertebrae and limb bones. Detected in chondrocytes and osteoblasts.3 Publications
Developmental stagei
Expression starts at 8 dpc in the developing heart. Higher expression in the brain is detected between 12 dpc and 16 dpc. High levels of expression in dorsal root ganglia and spinal nerves were observed throughout all developmental stages. In later developmental stages expression is more prominent in skeletal systems (at protein level).1 Publication
Inductioni
By hyaluronidase. Up-regulated in outer and inner nuclear layers during retinal degeneration.2 Publications
Gene expression databases
Bgeei | ENSMUSG00000004637, Expressed in visual cortex and 229 other tissues |
Genevisiblei | Q91WL8, MM |
Interactioni
Subunit structurei
Interacts with TP53, TP73/p73 and MAPK8.
Interacts with MAPT/TAU.
Forms a ternary complex with TP53 and MDM2 and interacts with ERBB4, LITAF and WBP1. May interact with FAM189B and SCOTIN (By similarity).
Interacts with HYAL2 and RUNX2.
Interacts with TNK2 (By similarity).
Interacts with TMEM207 (By similarity).
By similarityGO - Molecular functioni
- enzyme binding Source: BHF-UCL
- identical protein binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 219796, 4 interactors |
STRINGi | 10090.ENSMUSP00000004756 |
Miscellaneous databases
RNActi | Q91WL8, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 16 – 49 | WW 1PROSITE-ProRule annotationAdd BLAST | 34 | |
Domaini | 57 – 90 | WW 2PROSITE-ProRule annotationAdd BLAST | 34 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 125 – 414 | Interaction with MAPT1 PublicationAdd BLAST | 290 | |
Regioni | 209 – 273 | Mediates targeting to the mitochondriaAdd BLAST | 65 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 50 – 55 | Nuclear localization signal | 6 |
Domaini
The WW 1 domain mediates interaction with TP73, TFAP2C, LITAF, WBP1 and probably TP53.2 Publications
Sequence similaritiesi
Belongs to the short-chain dehydrogenases/reductases (SDR) family.Curated
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | KOG1208, Eukaryota |
GeneTreei | ENSGT00940000157389 |
HOGENOMi | CLU_010194_44_0_1 |
InParanoidi | Q91WL8 |
OMAi | DDGTVCY |
OrthoDBi | 1413827at2759 |
PhylomeDBi | Q91WL8 |
TreeFami | TF105428 |
Family and domain databases
CDDi | cd09809, human_WWOX_like_SDR_c-like, 1 hit cd00201, WW, 2 hits |
InterProi | View protein in InterPro IPR036291, NAD(P)-bd_dom_sf IPR002347, SDR_fam IPR001202, WW_dom IPR036020, WW_dom_sf IPR042732, WWOX_SDR_c-like |
Pfami | View protein in Pfam PF00106, adh_short, 1 hit PF00397, WW, 2 hits |
PRINTSi | PR00081, GDHRDH |
SMARTi | View protein in SMART SM00456, WW, 2 hits |
SUPFAMi | SSF51045, SSF51045, 2 hits SSF51735, SSF51735, 1 hit |
PROSITEi | View protein in PROSITE PS01159, WW_DOMAIN_1, 2 hits PS50020, WW_DOMAIN_2, 2 hits |
s (4)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: Q91WL8-1) [UniParc]FASTAAdd to basket
Also known as: Wox1
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAALRYAGLD DTDSEDELPP GWEERTTKDG WVYYANHTEE KTQWEHPKTG
60 70 80 90 100
KRKRVAGDLP YGWEQETDEN GQVFFVDHIN KRTTYLDPRL AFTVDDNPTK
110 120 130 140 150
PTTRQRYDGS TTAMEILQGR DFTGKVVLVT GANSGIGFET AKSFALHGAH
160 170 180 190 200
VILACRNLSR ASEAVSRILE EWHKAKVEAM TLDLAVLRSV QHFAEAFKAK
210 220 230 240 250
NVSLHVLVCN AGTFALPWGL TKDGLETTFQ VNHLGHFYLV QLLQDVLCRS
260 270 280 290 300
SPARVIVVSS ESHRFTDIND SSGKLDLSRL SPPRSDYWAM LAYNRSKLCN
310 320 330 340 350
ILFSNELHRR LSPRGVTSNA VHPGNMMYSA IHRNSWVYKL LFTLARPFTK
360 370 380 390 400
SMQQGAATTV YCAVAPELEG LGGMYFNNCC RCLPSEEAQS EETARALWEL
410
SERLIQDRLG SPSS
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 135 | G → V in BAB31244 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 231 | V → A in AAF31693 (PubMed:11058590).Curated | 1 | |
Sequence conflicti | 231 | V → A in AAL03972 (PubMed:11979549).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_016370 | 137 – 158 | GFETA…ACRNL → ALSPLLGERCIRRRQVLCSV FG in isoform 2. 1 PublicationAdd BLAST | 22 | |
Alternative sequenceiVSP_016371 | 159 – 414 | Missing in isoform 2. 1 PublicationAdd BLAST | 256 | |
Alternative sequenceiVSP_016372 | 353 – 367 | QQGAA…AVAPE → KPCMIGHTCDPNPRN in isoform 4. 1 PublicationAdd BLAST | 15 | |
Alternative sequenceiVSP_016373 | 353 – 354 | QQ → IL in isoform 3. 1 Publication | 2 | |
Alternative sequenceiVSP_016374 | 355 – 414 | Missing in isoform 3. 1 PublicationAdd BLAST | 60 | |
Alternative sequenceiVSP_016375 | 368 – 414 | Missing in isoform 4. 1 PublicationAdd BLAST | 47 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF187014 mRNA Translation: AAF31693.1 AK018507 mRNA Translation: BAB31244.1 AK019911 mRNA Translation: BAB31911.1 AK046903 mRNA Translation: BAC32916.1 AK078528 mRNA Translation: BAC37325.1 BC014716 mRNA Translation: AAH14716.1 AH011063 Genomic DNA Translation: AAL03972.1 |
CCDSi | CCDS22691.1 [Q91WL8-1] |
RefSeqi | NP_062519.2, NM_019573.3 [Q91WL8-1] XP_006531577.1, XM_006531514.3 [Q91WL8-3] XP_011246860.1, XM_011248558.2 [Q91WL8-4] |
Genome annotation databases
Ensembli | ENSMUST00000004756; ENSMUSP00000004756; ENSMUSG00000004637 [Q91WL8-1] ENSMUST00000109107; ENSMUSP00000104735; ENSMUSG00000004637 [Q91WL8-2] ENSMUST00000109108; ENSMUSP00000104736; ENSMUSG00000004637 [Q91WL8-4] ENSMUST00000160862; ENSMUSP00000125626; ENSMUSG00000004637 [Q91WL8-3] |
GeneIDi | 80707 |
KEGGi | mmu:80707 |
UCSCi | uc009noc.2, mouse [Q91WL8-2] uc009nod.2, mouse [Q91WL8-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF187014 mRNA Translation: AAF31693.1 AK018507 mRNA Translation: BAB31244.1 AK019911 mRNA Translation: BAB31911.1 AK046903 mRNA Translation: BAC32916.1 AK078528 mRNA Translation: BAC37325.1 BC014716 mRNA Translation: AAH14716.1 AH011063 Genomic DNA Translation: AAL03972.1 |
CCDSi | CCDS22691.1 [Q91WL8-1] |
RefSeqi | NP_062519.2, NM_019573.3 [Q91WL8-1] XP_006531577.1, XM_006531514.3 [Q91WL8-3] XP_011246860.1, XM_011248558.2 [Q91WL8-4] |
3D structure databases
SMRi | Q91WL8 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 219796, 4 interactors |
STRINGi | 10090.ENSMUSP00000004756 |
PTM databases
iPTMneti | Q91WL8 |
PhosphoSitePlusi | Q91WL8 |
SwissPalmi | Q91WL8 |
Proteomic databases
EPDi | Q91WL8 |
PaxDbi | Q91WL8 |
PeptideAtlasi | Q91WL8 |
PRIDEi | Q91WL8 |
ProteomicsDBi | 299997 [Q91WL8-1] 299998 [Q91WL8-2] 299999 [Q91WL8-3] 300000 [Q91WL8-4] |
Protocols and materials databases
Antibodypediai | 8291, 353 antibodies |
DNASUi | 80707 |
Genome annotation databases
Ensembli | ENSMUST00000004756; ENSMUSP00000004756; ENSMUSG00000004637 [Q91WL8-1] ENSMUST00000109107; ENSMUSP00000104735; ENSMUSG00000004637 [Q91WL8-2] ENSMUST00000109108; ENSMUSP00000104736; ENSMUSG00000004637 [Q91WL8-4] ENSMUST00000160862; ENSMUSP00000125626; ENSMUSG00000004637 [Q91WL8-3] |
GeneIDi | 80707 |
KEGGi | mmu:80707 |
UCSCi | uc009noc.2, mouse [Q91WL8-2] uc009nod.2, mouse [Q91WL8-1] |
Organism-specific databases
CTDi | 51741 |
MGIi | MGI:1931237, Wwox |
Phylogenomic databases
eggNOGi | KOG1208, Eukaryota |
GeneTreei | ENSGT00940000157389 |
HOGENOMi | CLU_010194_44_0_1 |
InParanoidi | Q91WL8 |
OMAi | DDGTVCY |
OrthoDBi | 1413827at2759 |
PhylomeDBi | Q91WL8 |
TreeFami | TF105428 |
Enzyme and pathway databases
Reactomei | R-MMU-1251985, Nuclear signaling by ERBB4 R-MMU-8866904, Negative regulation of activity of TFAP2 (AP-2) family transcription factors R-MMU-8866907, Activation of the TFAP2 (AP-2) family of transcription factors |
Miscellaneous databases
BioGRID-ORCSi | 80707, 1 hit in 52 CRISPR screens |
ChiTaRSi | Wwox, mouse |
PROi | PR:Q91WL8 |
RNActi | Q91WL8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000004637, Expressed in visual cortex and 229 other tissues |
Genevisiblei | Q91WL8, MM |
Family and domain databases
CDDi | cd09809, human_WWOX_like_SDR_c-like, 1 hit cd00201, WW, 2 hits |
InterProi | View protein in InterPro IPR036291, NAD(P)-bd_dom_sf IPR002347, SDR_fam IPR001202, WW_dom IPR036020, WW_dom_sf IPR042732, WWOX_SDR_c-like |
Pfami | View protein in Pfam PF00106, adh_short, 1 hit PF00397, WW, 2 hits |
PRINTSi | PR00081, GDHRDH |
SMARTi | View protein in SMART SM00456, WW, 2 hits |
SUPFAMi | SSF51045, SSF51045, 2 hits SSF51735, SSF51735, 1 hit |
PROSITEi | View protein in PROSITE PS01159, WW_DOMAIN_1, 2 hits PS50020, WW_DOMAIN_2, 2 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | WWOX_MOUSE | |
Accessioni | Q91WL8Primary (citable) accession number: Q91WL8 Secondary accession number(s): Q8C8J6 Q9JLF5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 22, 2005 |
Last sequence update: | December 1, 2001 | |
Last modified: | April 7, 2021 | |
This is version 165 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families