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Protein

WW domain-containing oxidoreductase

Gene

Wwox

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei260SubstrateBy similarity1
Active sitei293Proton acceptorBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi131 – 137NADPBy similarity7

GO - Molecular functioni

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 from RNA polymerase II promoter Source: BHF-UCL
  • skeletal system morphogenesis Source: MGI
  • Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Apoptosis, Wnt signaling pathway

Keywords - Ligandi

NADP

Enzyme and pathway databases

ReactomeiR-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
Recommended name:
WW domain-containing oxidoreductase (EC:1.1.1.-)
Gene namesi
Name:Wwox
Synonyms:Wox1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1931237. Wwox.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: MGI
  • Golgi apparatus Source: MGI
  • microvillus Source: Ensembl
  • mitochondrion Source: MGI
  • nucleus Source: BHF-UCL
  • plasma membrane Source: Ensembl
  • RNA polymerase II transcription factor complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

Pathology & 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 keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi51 – 54KRKR → QGTG: Abolishes the TNF-induced nuclear translocation. 1 Publication4

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000548161 – 414WW domain-containing oxidoreductaseAdd BLAST414

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei12PhosphothreonineCombined sources1
Modified residuei14PhosphoserineCombined sources1
Modified residuei33Phosphotyrosine1 Publication1
Modified residuei287Phosphotyrosine; by TNK2By similarity1

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 conjugation

Proteomic databases

EPDiQ91WL8.
PaxDbiQ91WL8.
PeptideAtlasiQ91WL8.
PRIDEiQ91WL8.

PTM databases

iPTMnetiQ91WL8.
PhosphoSitePlusiQ91WL8.

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 E8 in the developing heart. Higher expression in the brain is detected between E12 and E16. 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

BgeeiENSMUSG00000004637.
CleanExiMM_WWOX.
GenevisibleiQ91WL8. 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 similarity

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi219796. 4 interactors.
STRINGi10090.ENSMUSP00000004756.

Structurei

3D structure databases

ProteinModelPortaliQ91WL8.
SMRiQ91WL8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini16 – 49WW 1PROSITE-ProRule annotationAdd BLAST34
Domaini57 – 90WW 2PROSITE-ProRule annotationAdd BLAST34

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni125 – 414Interaction with MAPT1 PublicationAdd BLAST290
Regioni209 – 273Mediates targeting to the mitochondriaAdd BLAST65

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi50 – 55Nuclear localization signal6

Domaini

The WW 1 domain mediates interaction with TP73, TFAP2C, LITAF, WBP1 and probably TP53.2 Publications

Sequence similaritiesi

Contains 2 WW domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1208. Eukaryota.
COG1028. LUCA.
COG5021. LUCA.
GeneTreeiENSGT00760000119068.
HOGENOMiHOG000169779.
HOVERGENiHBG078800.
InParanoidiQ91WL8.
KOiK19329.
OMAiYSNIHRS.
OrthoDBiEOG091G0EI5.
PhylomeDBiQ91WL8.
TreeFamiTF105428.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR016040. NAD(P)-bd_dom.
IPR002347. SDR_fam.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00106. adh_short. 1 hit.
PF00397. WW. 2 hits.
[Graphical view]
PRINTSiPR00081. GDHRDH.
SMARTiSM00456. WW. 2 hits.
[Graphical view]
SUPFAMiSSF51045. SSF51045. 2 hits.
SSF51735. SSF51735. 1 hit.
PROSITEiPS01159. WW_DOMAIN_1. 2 hits.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q91WL8-1) [UniParc]FASTAAdd to basket
Also known as: Wox1

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.

« Hide

        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
Length:414
Mass (Da):46,512
Last modified:December 1, 2001 - v1
Checksum:i3C83AE3085B6A931
GO
Isoform 2 (identifier: Q91WL8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     137-158: GFETAKSFALHGAHVILACRNL → ALSPLLGERCIRRRQVLCSVFG
     159-414: Missing.

Note: No experimental confirmation available.
Show »
Length:158
Mass (Da):17,970
Checksum:iE9730E89E24FBFBD
GO
Isoform 3 (identifier: Q91WL8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     353-354: QQ → IL
     355-414: Missing.

Note: No experimental confirmation available.
Show »
Length:354
Mass (Da):40,018
Checksum:i41CBA77635E5E985
GO
Isoform 4 (identifier: Q91WL8-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     353-367: QQGAATTVYCAVAPE → KPCMIGHTCDPNPRN
     368-414: Missing.

Note: No experimental confirmation available.
Show »
Length:367
Mass (Da):41,457
Checksum:iFA7DA8F79742CB91
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti135G → V in BAB31244 (PubMed:16141072).Curated1
Sequence conflicti231V → A in AAF31693 (PubMed:11058590).Curated1
Sequence conflicti231V → A in AAL03972 (PubMed:11979549).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_016370137 – 158GFETA…ACRNL → ALSPLLGERCIRRRQVLCSV FG in isoform 2. 1 PublicationAdd BLAST22
Alternative sequenceiVSP_016371159 – 414Missing in isoform 2. 1 PublicationAdd BLAST256
Alternative sequenceiVSP_016372353 – 367QQGAA…AVAPE → KPCMIGHTCDPNPRN in isoform 4. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_016373353 – 354QQ → IL in isoform 3. 1 Publication2
Alternative sequenceiVSP_016374355 – 414Missing in isoform 3. 1 PublicationAdd BLAST60
Alternative sequenceiVSP_016375368 – 414Missing in isoform 4. 1 PublicationAdd BLAST47

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.
CCDSiCCDS22691.1. [Q91WL8-1]
RefSeqiNP_062519.2. NM_019573.3. [Q91WL8-1]
XP_006531577.1. XM_006531514.3. [Q91WL8-3]
XP_011246860.1. XM_011248558.2. [Q91WL8-4]
UniGeneiMm.440420.

Genome annotation databases

EnsembliENSMUST00000004756; ENSMUSP00000004756; ENSMUSG00000004637. [Q91WL8-1]
ENSMUST00000109107; ENSMUSP00000104735; ENSMUSG00000004637. [Q91WL8-2]
ENSMUST00000109108; ENSMUSP00000104736; ENSMUSG00000004637. [Q91WL8-4]
ENSMUST00000160862; ENSMUSP00000125626; ENSMUSG00000004637. [Q91WL8-3]
GeneIDi80707.
KEGGimmu:80707.
UCSCiuc009noc.2. mouse. [Q91WL8-2]
uc009nod.2. mouse. [Q91WL8-1]

Keywords - Coding sequence diversityi

Alternative splicing

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.
CCDSiCCDS22691.1. [Q91WL8-1]
RefSeqiNP_062519.2. NM_019573.3. [Q91WL8-1]
XP_006531577.1. XM_006531514.3. [Q91WL8-3]
XP_011246860.1. XM_011248558.2. [Q91WL8-4]
UniGeneiMm.440420.

3D structure databases

ProteinModelPortaliQ91WL8.
SMRiQ91WL8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi219796. 4 interactors.
STRINGi10090.ENSMUSP00000004756.

PTM databases

iPTMnetiQ91WL8.
PhosphoSitePlusiQ91WL8.

Proteomic databases

EPDiQ91WL8.
PaxDbiQ91WL8.
PeptideAtlasiQ91WL8.
PRIDEiQ91WL8.

Protocols and materials databases

DNASUi80707.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000004756; ENSMUSP00000004756; ENSMUSG00000004637. [Q91WL8-1]
ENSMUST00000109107; ENSMUSP00000104735; ENSMUSG00000004637. [Q91WL8-2]
ENSMUST00000109108; ENSMUSP00000104736; ENSMUSG00000004637. [Q91WL8-4]
ENSMUST00000160862; ENSMUSP00000125626; ENSMUSG00000004637. [Q91WL8-3]
GeneIDi80707.
KEGGimmu:80707.
UCSCiuc009noc.2. mouse. [Q91WL8-2]
uc009nod.2. mouse. [Q91WL8-1]

Organism-specific databases

CTDi51741.
MGIiMGI:1931237. Wwox.

Phylogenomic databases

eggNOGiKOG1208. Eukaryota.
COG1028. LUCA.
COG5021. LUCA.
GeneTreeiENSGT00760000119068.
HOGENOMiHOG000169779.
HOVERGENiHBG078800.
InParanoidiQ91WL8.
KOiK19329.
OMAiYSNIHRS.
OrthoDBiEOG091G0EI5.
PhylomeDBiQ91WL8.
TreeFamiTF105428.

Enzyme and pathway databases

ReactomeiR-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

ChiTaRSiWwox. mouse.
PROiQ91WL8.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000004637.
CleanExiMM_WWOX.
GenevisibleiQ91WL8. MM.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR016040. NAD(P)-bd_dom.
IPR002347. SDR_fam.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00106. adh_short. 1 hit.
PF00397. WW. 2 hits.
[Graphical view]
PRINTSiPR00081. GDHRDH.
SMARTiSM00456. WW. 2 hits.
[Graphical view]
SUPFAMiSSF51045. SSF51045. 2 hits.
SSF51735. SSF51735. 1 hit.
PROSITEiPS01159. WW_DOMAIN_1. 2 hits.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiWWOX_MOUSE
AccessioniPrimary (citable) accession number: Q91WL8
Secondary accession number(s): Q8C8J6
, Q920Y2, Q9D2B3, Q9D339, Q9JLF5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 22, 2005
Last sequence update: December 1, 2001
Last modified: November 30, 2016
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.