Q91WL8 · WWOX_MOUSE
- ProteinWW domain-containing oxidoreductase
- GeneWwox
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids414 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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
May also play a role in tumor necrosis factor (TNF)-mediated cell death. Required for normal bone development
Features
Showing features for binding site, active site.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameWW domain-containing oxidoreductase
- EC number
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ91WL8
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
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.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 51-54 | Abolishes the TNF-induced nuclear translocation. | ||||
Sequence: KRKR → QGTG |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 20 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000054816 | 1-414 | WW domain-containing oxidoreductase | |||
Sequence: MAALRYAGLDDTDSEDELPPGWEERTTKDGWVYYANHTEEKTQWEHPKTGKRKRVAGDLPYGWEQETDENGQVFFVDHINKRTTYLDPRLAFTVDDNPTKPTTRQRYDGSTTAMEILQGRDFTGKVVLVTGANSGIGFETAKSFALHGAHVILACRNLSRASEAVSRILEEWHKAKVEAMTLDLAVLRSVQHFAEAFKAKNVSLHVLVCNAGTFALPWGLTKDGLETTFQVNHLGHFYLVQLLQDVLCRSSPARVIVVSSESHRFTDINDSSGKLDLSRLSPPRSDYWAMLAYNRSKLCNILFSNELHRRLSPRGVTSNAVHPGNMMYSAIHRNSWVYKLLFTLARPFTKSMQQGAATTVYCAVAPELEGLGGMYFNNCCRCLPSEEAQSEETARALWELSERLIQDRLGSPSS | ||||||
Modified residue | 12 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 14 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 33 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 287 | Phosphotyrosine; by TNK2 | ||||
Sequence: Y |
Post-translational modification
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).
Ubiquitinated when phosphorylated by TNK2, leading to its degradation.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
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.
Induction
By hyaluronidase. Up-regulated in outer and inner nuclear layers during retinal degeneration.
Developmental stage
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).
Gene expression databases
Interaction
Subunit
Interacts with TP53, p73/TP73 and MAPK8 (PubMed:11058590, PubMed:12514174).
Interacts with MAPT/TAU, RUNX2 and HYAL2 (By similarity) (PubMed:15126504, PubMed:16219768).
Forms a ternary complex with TP53 and MDM2 (By similarity).
Interacts with ERBB4, LITAF and WBP1. Interacts with DVL1, DVL2 and DVL3. May interact with FAM189B and SCOTIN. Interacts with TNK2. Interacts with TMEM207 (By similarity).
Interacts (via WW domain) with VOPP1 (By similarity).
Interacts with MAPT/TAU, RUNX2 and HYAL2 (By similarity) (PubMed:15126504, PubMed:16219768).
Forms a ternary complex with TP53 and MDM2 (By similarity).
Interacts with ERBB4, LITAF and WBP1. Interacts with DVL1, DVL2 and DVL3. May interact with FAM189B and SCOTIN. Interacts with TNK2. Interacts with TMEM207 (By similarity).
Interacts (via WW domain) with VOPP1 (By similarity).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-24 | Disordered | ||||
Sequence: MAALRYAGLDDTDSEDELPPGWEE | ||||||
Domain | 16-49 | WW 1 | ||||
Sequence: DELPPGWEERTTKDGWVYYANHTEEKTQWEHPKT | ||||||
Motif | 50-55 | Nuclear localization signal | ||||
Sequence: GKRKRV | ||||||
Domain | 57-90 | WW 2 | ||||
Sequence: GDLPYGWEQETDENGQVFFVDHINKRTTYLDPRL | ||||||
Region | 125-414 | Interaction with MAPT | ||||
Sequence: KVVLVTGANSGIGFETAKSFALHGAHVILACRNLSRASEAVSRILEEWHKAKVEAMTLDLAVLRSVQHFAEAFKAKNVSLHVLVCNAGTFALPWGLTKDGLETTFQVNHLGHFYLVQLLQDVLCRSSPARVIVVSSESHRFTDINDSSGKLDLSRLSPPRSDYWAMLAYNRSKLCNILFSNELHRRLSPRGVTSNAVHPGNMMYSAIHRNSWVYKLLFTLARPFTKSMQQGAATTVYCAVAPELEGLGGMYFNNCCRCLPSEEAQSEETARALWELSERLIQDRLGSPSS | ||||||
Region | 209-273 | Mediates targeting to the mitochondria | ||||
Sequence: CNAGTFALPWGLTKDGLETTFQVNHLGHFYLVQLLQDVLCRSSPARVIVVSSESHRFTDINDSSG |
Domain
The WW 1 domain mediates interaction with TP73, TFAP2C, LITAF, WBP1 and probably TP53.
Sequence similarities
Belongs to the short-chain dehydrogenases/reductases (SDR) family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 4 isoforms produced by Alternative splicing.
Q91WL8-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- SynonymsWox1
- Length414
- Mass (Da)46,512
- Last updated2001-12-01 v1
- Checksum3C83AE3085B6A931
Q91WL8-2
- Name2
Q91WL8-3
- Name3
Q91WL8-4
- Name4
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 135 | in Ref. 2; BAB31244 | ||||
Sequence: G → V | ||||||
Alternative sequence | VSP_016370 | 137-158 | in isoform 2 | |||
Sequence: GFETAKSFALHGAHVILACRNL → ALSPLLGERCIRRRQVLCSVFG | ||||||
Alternative sequence | VSP_016371 | 159-414 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 231 | in Ref. 1; AAF31693 and 4; AAL03972 | ||||
Sequence: V → A | ||||||
Alternative sequence | VSP_016373 | 353-354 | in isoform 3 | |||
Sequence: QQ → IL | ||||||
Alternative sequence | VSP_016372 | 353-367 | in isoform 4 | |||
Sequence: QQGAATTVYCAVAPE → KPCMIGHTCDPNPRN | ||||||
Alternative sequence | VSP_016374 | 355-414 | in isoform 3 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_016375 | 368-414 | in isoform 4 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF187014 EMBL· GenBank· DDBJ | AAF31693.1 EMBL· GenBank· DDBJ | mRNA | ||
AK018507 EMBL· GenBank· DDBJ | BAB31244.1 EMBL· GenBank· DDBJ | mRNA | ||
AK019911 EMBL· GenBank· DDBJ | BAB31911.1 EMBL· GenBank· DDBJ | mRNA | ||
AK046903 EMBL· GenBank· DDBJ | BAC32916.1 EMBL· GenBank· DDBJ | mRNA | ||
AK078528 EMBL· GenBank· DDBJ | BAC37325.1 EMBL· GenBank· DDBJ | mRNA | ||
BC014716 EMBL· GenBank· DDBJ | AAH14716.1 EMBL· GenBank· DDBJ | mRNA | ||
AH011063 EMBL· GenBank· DDBJ | AAL03972.1 EMBL· GenBank· DDBJ | Genomic DNA |