Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Q9NZC7

- WWOX_HUMAN

UniProt

Q9NZC7 - WWOX_HUMAN

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

WW domain-containing oxidoreductase

Gene

WWOX

Organism
Homo sapiens (Human)
Status
Reviewed - 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. Required for normal bone development (By similarity). May function synergistically with p53/TP53 to control genotoxic stress-induced cell death. Plays a role in TGFB1 signaling and TGFB1-mediated cell death. May also play a role in tumor necrosis factor (TNF)-mediated cell death. Inhibits Wnt signaling, probably by sequestering DVL2 in the cytoplasm.By similarity7 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei260 – 2601SubstrateBy similarity
Active sitei293 – 2931Proton acceptorBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi131 – 1377NADPBy similarity

GO - Molecular functioni

  1. coenzyme binding Source: UniProtKB
  2. cofactor binding Source: UniProtKB
  3. enzyme binding Source: BHF-UCL
  4. oxidoreductase activity Source: UniProtKB
  5. protein dimerization activity Source: UniProtKB

GO - Biological processi

  1. cellular response to transforming growth factor beta stimulus Source: BHF-UCL
  2. extrinsic apoptotic signaling pathway Source: Ensembl
  3. intrinsic apoptotic signaling pathway by p53 class mediator Source: Ensembl
  4. negative regulation of Wnt signaling pathway Source: UniProtKB
  5. osteoblast differentiation Source: Ensembl
  6. oxidation-reduction process Source: UniProtKB
  7. positive regulation of extrinsic apoptotic signaling pathway Source: BHF-UCL
  8. positive regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
  9. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  10. skeletal system morphogenesis Source: BHF-UCL
  11. steroid metabolic process Source: UniProtKB
  12. 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

ReactomeiREACT_116022. Nuclear signaling by ERBB4.
SignaLinkiQ9NZC7.

Names & Taxonomyi

Protein namesi
Recommended name:
WW domain-containing oxidoreductase (EC:1.1.1.-)
Alternative name(s):
Fragile site FRA16D oxidoreductase
Gene namesi
Name:WWOX
Synonyms:FOR, WOX1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 16

Organism-specific databases

HGNCiHGNC:12799. WWOX.

Subcellular locationi

Cytoplasm. Nucleus. Mitochondrion. Golgi apparatus
Note: Partially localizes to the mitochondria. Translocates to the nucleus upon genotoxic stress or TNF stimulation (By similarity). Translocates to the nucleus in response to TGFB1. Isoform 5 and isoform 6 may localize in the nucleus.By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytosol Source: BHF-UCL
  3. Golgi apparatus Source: UniProtKB
  4. mitochondrion Source: BHF-UCL
  5. nucleus Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Golgi apparatus, Mitochondrion, Nucleus

Pathology & Biotechi

Involvement in diseasei

Defects in WWOX may be involved in several cancer types. The gene spans the second most common chromosomal fragile site (FRA16D) which is frequently altered in cancers. Alteration of the expression and expression of some isoforms is associated with cancers. However, it is still unclear if alteration of WWOX is directly implicated in cancerogenesis or if it corresponds to a secondary effect.
Esophageal cancer (ESCR) [MIM:133239]: A malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage.
Note: The disease may be caused by mutations affecting the gene represented in this entry.
Spinocerebellar ataxia, autosomal recessive, 12 (SCAR12) [MIM:614322]: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR12 is additionally characterized by onset of generalized seizures in infancy, and delayed psychomotor development with mental retardation. Some patients may also show spasticity.2 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti47 – 471P → T in SCAR12. 1 Publication
VAR_070992
Natural varianti372 – 3721G → R in SCAR12. 1 Publication
VAR_070993

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi28 – 281K → T: No effect on interaction with TP53. Abolishes interaction with MAPK8; when associated with V-29. 1 Publication
Mutagenesisi29 – 291D → V: No effect on interaction with TP53. Abolishes interaction with MAPK8; when associated with T-28. 1 Publication
Mutagenesisi33 – 331Y → F: Loss of phosphorylation. 2 Publications
Mutagenesisi33 – 331Y → R: Abolishes interaction with TP53, TP73, MAPK8 and ERBB4. Partial loss of interaction with TFAP2C. Loss of phosphorylation. Loss of the proapoptotic activity. 2 Publications
Mutagenesisi44 – 474WEHP → FEHA: Abolishes interaction with LITAF. 1 Publication
Mutagenesisi61 – 611Y → R: No effect on interaction with TP73. 1 Publication
Mutagenesisi85 – 884YLDP → ALDA: No effect on interaction with LITAF. 1 Publication
Mutagenesisi287 – 2871Y → A: Loss of phosphorylation by TNK2. 1 Publication

Keywords - Diseasei

Disease mutation, Neurodegeneration, Tumor suppressor

Organism-specific databases

MIMi133239. phenotype.
614322. phenotype.
Orphaneti251510. 46,XY partial gonadal dysgenesis.
284282. Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to WWOX deficiency.
PharmGKBiPA37398.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 414414WW domain-containing oxidoreductasePRO_0000054815Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei12 – 121Phosphothreonine1 Publication
Modified residuei14 – 141Phosphoserine1 Publication
Modified residuei33 – 331Phosphotyrosine2 Publications
Modified residuei287 – 2871Phosphotyrosine; by TNK21 Publication

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.3 Publications
Ubiquitinated when phosphorylated by TNK2, leading to its degradation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ9NZC7.
PaxDbiQ9NZC7.
PRIDEiQ9NZC7.

PTM databases

PhosphoSiteiQ9NZC7.

Expressioni

Tissue specificityi

Widely expressed. Strongly expressed in testis, prostate, and ovary. Overexpressed in cancer cell lines. Isoform 5 and isoform 6 may only be expressed in tumor cell lines.2 Publications

Gene expression databases

BgeeiQ9NZC7.
ExpressionAtlasiQ9NZC7. baseline and differential.
GenevestigatoriQ9NZC7.

Organism-specific databases

HPAiHPA050992.

Interactioni

Subunit structurei

Interacts with TP53, p73/TP73 and MAPK8. Interacts with MAPT/TAU, RUNX2 and HYAL2 (By similarity). Forms a ternary complex with TP53 and MDM2. 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 similarity10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Erbb4Q615273EBI-4320739,EBI-4398741From a different organism.
FAM189BP814082EBI-4320739,EBI-6366314
LITAFQ997325EBI-4320739,EBI-725647
SHISA5Q8N1142EBI-4320739,EBI-2115556
WBP1Q96G273EBI-4320739,EBI-3867685

Protein-protein interaction databases

BioGridi119707. 236 interactions.
IntActiQ9NZC7. 6 interactions.
MINTiMINT-1175612.

Structurei

Secondary structure

1
414
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi63 – 675Combined sources
Beta strandi73 – 808Combined sources
Beta strandi83 – 864Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1WMVNMR-A51-101[»]
ProteinModelPortaliQ9NZC7.
SMRiQ9NZC7. Positions 13-101, 121-327.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9NZC7.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini16 – 4934WW 1PROSITE-ProRule annotationAdd
BLAST
Domaini57 – 9034WW 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni125 – 414290Interaction with MAPTBy similarityAdd
BLAST
Regioni209 – 27365Mediates targeting to the mitochondriaBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi50 – 556Nuclear localization signalBy similarity

Domaini

The WW 1 domain mediates interaction with TP53, and probably TP73, TFAP2C, LITAF and WBP1.3 Publications

Sequence similaritiesi

Contains 2 WW domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiCOG1028.
GeneTreeiENSGT00760000119068.
HOVERGENiHBG078800.
InParanoidiQ9NZC7.
OMAiYSNIHRS.
OrthoDBiEOG73Z2TK.
PhylomeDBiQ9NZC7.
TreeFamiTF105428.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR002198. DH_sc/Rdtase_SDR.
IPR002347. Glc/ribitol_DH.
IPR016040. NAD(P)-bd_dom.
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.
PROSITEiPS01159. WW_DOMAIN_1. 2 hits.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view]

Sequences (7)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q9NZC7-1) [UniParc]FASTAAdd to Basket

Also known as: FOR II, FOR2, WWOXv1, WWOX v8

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 DFTGKVVVVT GANSGIGFET AKSFALHGAH
160 170 180 190 200
VILACRNMAR ASEAVSRILE EWHKAKVEAM TLDLALLRSV QHFAEAFKAK
210 220 230 240 250
NVPLHVLVCN AATFALPWSL TKDGLETTFQ VNHLGHFYLV QLLQDVLCRS
260 270 280 290 300
APARVIVVSS ESHRFTDIND SLGKLDFSRL SPTKNDYWAM LAYNRSKLCN
310 320 330 340 350
ILFSNELHRR LSPRGVTSNA VHPGNMMYSN IHRSWWVYTL LFTLARPFTK
360 370 380 390 400
SMQQGAATTV YCAAVPELEG LGGMYFNNCC RCMPSPEAQS EETARTLWAL
410
SERLIQERLG SQSG
Length:414
Mass (Da):46,677
Last modified:October 1, 2000 - v1
Checksum:iE4D9A649E6CB05DF
GO
Isoform 2 (identifier: Q9NZC7-2) [UniParc]FASTAAdd to Basket

Also known as: FOR I, FOR1, WOX2, WWOXv2

The sequence of this isoform differs from the canonical sequence as follows:
     353-363: QQGAATTVYCA → VSDCLVEGGHF
     364-414: Missing.

Show »
Length:363
Mass (Da):41,128
Checksum:iC1BB208B887281C3
GO
Isoform 3 (identifier: Q9NZC7-3) [UniParc]FASTAAdd to Basket

Also known as: FOR III, FOR3, WOX3

The sequence of this isoform differs from the canonical sequence as follows:
     173-189: HKAKVEAMTLDLALLRS → KTKYHPPPEKCRIKIFH
     190-414: Missing.

Show »
Length:189
Mass (Da):21,559
Checksum:i82155A9AD7C824C7
GO
Isoform 4 (identifier: Q9NZC7-4) [UniParc]FASTAAdd to Basket

Also known as: FOR IV

The sequence of this isoform differs from the canonical sequence as follows:
     36-36: N → K
     37-414: Missing.

Show »
Length:36
Mass (Da):4,150
Checksum:iA6D0FEE1CAE266B2
GO
Isoform 5 (identifier: Q9NZC7-5) [UniParc]FASTAAdd to Basket

Also known as: WWOXdelta6-8, WWOXv4

The sequence of this isoform differs from the canonical sequence as follows:
     173-352: Missing.

Show »
Length:234
Mass (Da):26,148
Checksum:iC69FB6B3E87635F4
GO
Isoform 6 (identifier: Q9NZC7-6) [UniParc]FASTAAdd to Basket

Also known as: WWOXdelta5-8, WWOXv3

The sequence of this isoform differs from the canonical sequence as follows:
     137-414: GFETAKSFAL...IQERLGSQSG → ATGSCHHRVL...FSFFYCYRIA

Show »
Length:311
Mass (Da):35,042
Checksum:i8EF6B9823F90C9F7
GO
Isoform 7 (identifier: Q9NZC7-7) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     138-213: FETAKSFALH...LHVLVCNAAT → KASCHVGRTL...PGPCGRSARG
     214-414: Missing.

Show »
Length:213
Mass (Da):23,868
Checksum:iA21054FF8214CC7C
GO

Sequence cautioni

The sequence AAP94227.1 differs from that shown. Reason: Frameshift at position 362. Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti47 – 471P → T in SCAR12. 1 Publication
VAR_070992
Natural varianti98 – 981P → L.1 Publication
Corresponds to variant rs144601717 [ dbSNP | Ensembl ].
VAR_023916
Natural varianti111 – 1111T → S in a Burkitt lymphoma cell line. 1 Publication
Corresponds to variant rs114755364 [ dbSNP | Ensembl ].
VAR_023917
Natural varianti120 – 1201R → W in a primary colorectal tumor and a histiocytic lymphoma cell line. 1 Publication
Corresponds to variant rs141361080 [ dbSNP | Ensembl ].
VAR_023918
Natural varianti179 – 1791A → T.2 Publications
Corresponds to variant rs12918952 [ dbSNP | Ensembl ].
VAR_023919
Natural varianti216 – 2161L → V.
Corresponds to variant rs7201683 [ dbSNP | Ensembl ].
VAR_052323
Natural varianti272 – 2721L → F.1 Publication
Corresponds to variant rs186745328 [ dbSNP | Ensembl ].
VAR_023920
Natural varianti282 – 2821P → A.1 Publication
Corresponds to variant rs3764340 [ dbSNP | Ensembl ].
VAR_023921
Natural varianti291 – 2911L → P Found in a esophageal cancer sample; somatic mutation. 1 Publication
VAR_023922
Natural varianti314 – 3141R → H in a cervical carcinoma cell line. 1 Publication
Corresponds to variant rs73572838 [ dbSNP | Ensembl ].
VAR_023923
Natural varianti372 – 3721G → R in SCAR12. 1 Publication
VAR_070993
Isoform 3 (identifier: Q9NZC7-3)
Natural varianti182 – 1821K → E Found in a primary colorectal tumor and tumor cells.

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei36 – 361N → K in isoform 4. 1 PublicationVSP_016358
Alternative sequencei37 – 414378Missing in isoform 4. 1 PublicationVSP_016359Add
BLAST
Alternative sequencei137 – 414278GFETA…GSQSG → ATGSCHHRVLCCCPRTGGSG RDVLQQLLPLHALTRSSERR DGPDPVGAQREADPRTAWQP VRLSGAQSGWAHTPALCVSP HASARAGPLPNVPPTQIRKS KGNKSSHNRVKNLKYQWEAG NSWGKVSLFWGWARHRSLCF LVVACLKVKTCLVCRFRISL EKHQQFSFFYCYRIA in isoform 6. 1 PublicationVSP_016360Add
BLAST
Alternative sequencei138 – 21376FETAK…CNAAT → KASCHVGRTLKHTRVEELSL LPTAINRELPPPCTVLLSQN WRVWEGCTSTTAAAACPHQK LRAKRRPGPCGRSARG in isoform 7. CuratedVSP_016362Add
BLAST
Alternative sequencei173 – 352180Missing in isoform 5. 3 PublicationsVSP_016363Add
BLAST
Alternative sequencei173 – 18917HKAKV…ALLRS → KTKYHPPPEKCRIKIFH in isoform 3. 1 PublicationVSP_016364Add
BLAST
Alternative sequencei190 – 414225Missing in isoform 3. 1 PublicationVSP_016365Add
BLAST
Alternative sequencei214 – 414201Missing in isoform 7. CuratedVSP_016366Add
BLAST
Alternative sequencei353 – 36311QQGAATTVYCA → VSDCLVEGGHF in isoform 2. 1 PublicationVSP_016367Add
BLAST
Alternative sequencei364 – 41451Missing in isoform 2. 1 PublicationVSP_016369Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF211943 mRNA. Translation: AAF27049.1.
AF212843 Genomic DNA. Translation: AAF27050.1.
AH009490 Genomic DNA. Translation: AAF78197.1.
AF227526 mRNA. Translation: AAF82053.1.
AF227527 mRNA. Translation: AAF82054.1.
AF227528 mRNA. Translation: AAF82055.1.
AF227529 mRNA. Translation: AAF82056.1.
AF395123 mRNA. Translation: AAK81727.1.
AF395124 mRNA. Translation: AAK81728.1.
AF325432
, AF325423, AF325424, AF325425, AF325426, AF325427, AF325428, AF325430, AF325431 Genomic DNA. Translation: AAL05449.1.
AF325429
, AF325423, AF325424, AF325425, AF325426, AF325427 Genomic DNA. Translation: AAL05450.1.
AF325432
, AF325423, AF325424, AF325425, AF325426, AF325433 Genomic DNA. Translation: AAL05451.1.
AY256821 mRNA. Translation: AAP94227.1. Frameshift.
AK290438 mRNA. Translation: BAF83127.1.
BT007445 mRNA. Translation: AAP36113.1.
BC003184 mRNA. Translation: AAH03184.1.
CCDSiCCDS42196.1. [Q9NZC7-1]
CCDS42197.1. [Q9NZC7-3]
RefSeqiNP_001278926.1. NM_001291997.1.
NP_057457.1. NM_016373.3. [Q9NZC7-1]
NP_570607.1. NM_130791.3. [Q9NZC7-3]
UniGeneiHs.461453.

Genome annotation databases

EnsembliENST00000355860; ENSP00000348119; ENSG00000186153. [Q9NZC7-3]
ENST00000402655; ENSP00000384238; ENSG00000186153. [Q9NZC7-6]
ENST00000406884; ENSP00000384495; ENSG00000186153. [Q9NZC7-5]
ENST00000408984; ENSP00000386161; ENSG00000186153. [Q9NZC7-2]
ENST00000566780; ENSP00000457230; ENSG00000186153. [Q9NZC7-1]
ENST00000569818; ENSP00000454485; ENSG00000186153. [Q9NZC7-4]
GeneIDi51741.
KEGGihsa:51741.
UCSCiuc002ffi.2. human. [Q9NZC7-4]
uc002ffj.2. human. [Q9NZC7-3]
uc002ffk.3. human. [Q9NZC7-1]
uc002ffl.3. human. [Q9NZC7-5]
uc010che.3. human. [Q9NZC7-6]

Polymorphism databases

DMDMi74725363.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF211943 mRNA. Translation: AAF27049.1 .
AF212843 Genomic DNA. Translation: AAF27050.1 .
AH009490 Genomic DNA. Translation: AAF78197.1 .
AF227526 mRNA. Translation: AAF82053.1 .
AF227527 mRNA. Translation: AAF82054.1 .
AF227528 mRNA. Translation: AAF82055.1 .
AF227529 mRNA. Translation: AAF82056.1 .
AF395123 mRNA. Translation: AAK81727.1 .
AF395124 mRNA. Translation: AAK81728.1 .
AF325432
, AF325423 , AF325424 , AF325425 , AF325426 , AF325427 , AF325428 , AF325430 , AF325431 Genomic DNA. Translation: AAL05449.1 .
AF325429
, AF325423 , AF325424 , AF325425 , AF325426 , AF325427 Genomic DNA. Translation: AAL05450.1 .
AF325432
, AF325423 , AF325424 , AF325425 , AF325426 , AF325433 Genomic DNA. Translation: AAL05451.1 .
AY256821 mRNA. Translation: AAP94227.1 . Frameshift.
AK290438 mRNA. Translation: BAF83127.1 .
BT007445 mRNA. Translation: AAP36113.1 .
BC003184 mRNA. Translation: AAH03184.1 .
CCDSi CCDS42196.1. [Q9NZC7-1 ]
CCDS42197.1. [Q9NZC7-3 ]
RefSeqi NP_001278926.1. NM_001291997.1.
NP_057457.1. NM_016373.3. [Q9NZC7-1 ]
NP_570607.1. NM_130791.3. [Q9NZC7-3 ]
UniGenei Hs.461453.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1WMV NMR - A 51-101 [» ]
ProteinModelPortali Q9NZC7.
SMRi Q9NZC7. Positions 13-101, 121-327.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 119707. 236 interactions.
IntActi Q9NZC7. 6 interactions.
MINTi MINT-1175612.

PTM databases

PhosphoSitei Q9NZC7.

Polymorphism databases

DMDMi 74725363.

Proteomic databases

MaxQBi Q9NZC7.
PaxDbi Q9NZC7.
PRIDEi Q9NZC7.

Protocols and materials databases

DNASUi 51741.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000355860 ; ENSP00000348119 ; ENSG00000186153 . [Q9NZC7-3 ]
ENST00000402655 ; ENSP00000384238 ; ENSG00000186153 . [Q9NZC7-6 ]
ENST00000406884 ; ENSP00000384495 ; ENSG00000186153 . [Q9NZC7-5 ]
ENST00000408984 ; ENSP00000386161 ; ENSG00000186153 . [Q9NZC7-2 ]
ENST00000566780 ; ENSP00000457230 ; ENSG00000186153 . [Q9NZC7-1 ]
ENST00000569818 ; ENSP00000454485 ; ENSG00000186153 . [Q9NZC7-4 ]
GeneIDi 51741.
KEGGi hsa:51741.
UCSCi uc002ffi.2. human. [Q9NZC7-4 ]
uc002ffj.2. human. [Q9NZC7-3 ]
uc002ffk.3. human. [Q9NZC7-1 ]
uc002ffl.3. human. [Q9NZC7-5 ]
uc010che.3. human. [Q9NZC7-6 ]

Organism-specific databases

CTDi 51741.
GeneCardsi GC16P078133.
HGNCi HGNC:12799. WWOX.
HPAi HPA050992.
MIMi 133239. phenotype.
605131. gene.
614322. phenotype.
neXtProti NX_Q9NZC7.
Orphaneti 251510. 46,XY partial gonadal dysgenesis.
284282. Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to WWOX deficiency.
PharmGKBi PA37398.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG1028.
GeneTreei ENSGT00760000119068.
HOVERGENi HBG078800.
InParanoidi Q9NZC7.
OMAi YSNIHRS.
OrthoDBi EOG73Z2TK.
PhylomeDBi Q9NZC7.
TreeFami TF105428.

Enzyme and pathway databases

Reactomei REACT_116022. Nuclear signaling by ERBB4.
SignaLinki Q9NZC7.

Miscellaneous databases

ChiTaRSi WWOX. human.
EvolutionaryTracei Q9NZC7.
GeneWikii WWOX.
GenomeRNAii 51741.
NextBioi 55812.
PROi Q9NZC7.
SOURCEi Search...

Gene expression databases

Bgeei Q9NZC7.
ExpressionAtlasi Q9NZC7. baseline and differential.
Genevestigatori Q9NZC7.

Family and domain databases

Gene3Di 3.40.50.720. 1 hit.
InterProi IPR002198. DH_sc/Rdtase_SDR.
IPR002347. Glc/ribitol_DH.
IPR016040. NAD(P)-bd_dom.
IPR001202. WW_dom.
[Graphical view ]
Pfami PF00106. adh_short. 1 hit.
PF00397. WW. 2 hits.
[Graphical view ]
PRINTSi PR00081. GDHRDH.
SMARTi SM00456. WW. 2 hits.
[Graphical view ]
SUPFAMi SSF51045. SSF51045. 2 hits.
PROSITEi PS01159. WW_DOMAIN_1. 2 hits.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "WWOX, a novel WW domain-containing protein mapping to human chromosome 16q23.3-24.1, a region frequently affected in breast cancer."
    Bednarek A.K., Laflin K.J., Daniel R.L., Liao Q., Hawkins K.A., Aldaz C.M.
    Cancer Res. 60:2140-2145(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-35, TISSUE SPECIFICITY.
    Tissue: Placenta.
  2. "Common chromosomal fragile site FRA16D sequence: identification of the FOR gene spanning FRA16D and homozygous deletions and translocation breakpoints in cancer cells."
    Ried K., Finnis M., Hobson L., Mangelsdorf M., Dayan S., Nancarrow J.K., Woollatt E., Kremmidiotis G., Gardner A., Venter D., Baker E., Richards R.I.
    Hum. Mol. Genet. 9:1651-1663(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 173-414.
  3. "WWOX, the FRA16D gene, behaves as a suppressor of tumor growth."
    Bednarek A.K., Keck-Waggoner C.L., Daniel R.L., Laflin K.J., Bergsagel P.L., Kiguchi K., Brenner A.J., Aldaz C.M.
    Cancer Res. 61:8068-8073(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5 AND 6), FUNCTION, TISSUE SPECIFICITY.
  4. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS 1; 3 AND 7), VARIANTS LEU-98; SER-111; TRP-120; THR-179; PHE-272; ALA-282 AND HIS-314, DISEASE.
  5. "Cloning of human WOX8 (WWOX v8)."
    Chang N.-S.
    Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT THR-179.
    Tissue: Colon adenocarcinoma.
  6. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  7. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
  8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
    Tissue: Lung.
  9. "An opposing view on WWOX protein function as a tumor suppressor."
    Watanabe A., Hippo Y., Taniguchi H., Iwanari H., Yashiro M., Hirakawa K., Kodama T., Aburatani H.
    Cancer Res. 63:8629-8633(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  10. "JNK1 physically interacts with WW domain-containing oxidoreductase (WOX1) and inhibits WOX1-mediated apoptosis."
    Chang N.-S., Doherty J., Ensign A.
    J. Biol. Chem. 278:9195-9202(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MAPK8 AND TP53, MUTAGENESIS OF LYS-28; ASP-29 AND TYR-33.
  11. "Frequent downregulation and loss of WWOX gene expression in human hepatocellular carcinoma."
    Park S.-W., Ludes-Meyers J., Zimonjic D.B., Durkin M.E., Popescu N.C., Aldaz C.M.
    Br. J. Cancer 91:753-759(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISEASE.
  12. "Physical and functional interactions between the Wwox tumor suppressor protein and the AP-2gamma transcription factor."
    Aqeilan R.I., Palamarchuk A., Weigel R.J., Herrero J.J., Pekarsky Y., Croce C.M.
    Cancer Res. 64:8256-8261(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH TFAP2C AND TFAP2A, DOMAIN.
  13. Cited for: DISEASE.
  14. Cited for: DISEASE.
  15. "WWOX binds the specific proline-rich ligand PPXY: identification of candidate interacting proteins."
    Ludes-Meyers J.H., Kil H., Bednarek A.K., Drake J., Bedford M.T., Aldaz C.M.
    Oncogene 23:5049-5055(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH LITAF; WBP1; FAM189B AND SCOTIN, MUTAGENESIS OF 44-TRP--PRO-47 AND 85-TYR--PRO-88, DOMAIN, SUBCELLULAR LOCATION.
  16. Cited for: FUNCTION, INTERACTION WITH TP73, DOMAIN, MUTAGENESIS OF TYR-33 AND TYR-61, PHOSPHORYLATION AT TYR-33, SUBCELLULAR LOCATION.
  17. "WW domain-containing proteins, WWOX and YAP, compete for interaction with ErbB-4 and modulate its transcriptional function."
    Aqeilan R.I., Donati V., Palamarchuk A., Trapasso F., Kaou M., Pekarsky Y., Sudol M., Croce C.M.
    Cancer Res. 65:6764-6772(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH ERBB4.
  18. "Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox."
    Mahajan N.P., Whang Y.E., Mohler J.L., Earp H.S.
    Cancer Res. 65:10514-10523(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT TYR-287 BY TNK2, UBIQUITINATION, MUTAGENESIS OF TYR-287, INTERACTION WITH TNK2.
  19. "WOX1 is essential for tumor necrosis factor-, UV light-, staurosporine-, and p53-mediated cell death, and its tyrosine 33-phosphorylated form binds and stabilizes serine 46-phosphorylated p53."
    Chang N.-S., Doherty J., Ensign A., Schultz L., Hsu L.-J., Hong Q.
    J. Biol. Chem. 280:43100-43108(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH MDM2 AND TP53, PHOSPHORYLATION, SUBCELLULAR LOCATION.
  20. Cited for: DISEASE.
  21. "Transforming growth factor beta1 signaling via interaction with cell surface Hyal-2 and recruitment of WWOX/WOX1."
    Hsu L.-J., Schultz L., Hong Q., Van Moer K., Heath J., Li M.-Y., Lai F.-J., Lin S.-R., Lee M.-H., Lo C.-P., Lin Y.-S., Chen S.-T., Chang N.-S.
    J. Biol. Chem. 284:16049-16059(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PHOSPHORYLATION AT TYR-33, SUBCELLULAR LOCATION, INTERACTION WITH HYAL2.
  22. "Inhibition of the Wnt/beta-catenin pathway by the WWOX tumor suppressor protein."
    Bouteille N., Driouch K., Hage P.E., Sin S., Formstecher E., Camonis J., Lidereau R., Lallemand F.
    Oncogene 28:2569-2580(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH DVL1; DVL2 AND DVL3.
  23. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-12 AND SER-14, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  24. "A WWOX-binding molecule, transmembrane protein 207, is related to the invasiveness of gastric signet-ring cell carcinoma."
    Takeuchi T., Adachi Y., Nagayama T.
    Carcinogenesis 33:548-554(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TMEM207.
  25. "The supposed tumor suppressor gene WWOX is mutated in an early lethal microcephaly syndrome with epilepsy, growth retardation and retinal degeneration."
    Abdel-Salam G., Thoenes M., Afifi H.H., Koerber F., Swan D., Bolz H.J.
    Orphanet J. Rare Dis. 9:12-12(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN SCAR12.
  26. "Solution structure of the second WW domain of WWOX."
    Kowalski K., Merkel A.L., Colella A., Richards R.I., Booker G.W.
    Submitted (FEB-2009) to the PDB data bank
    Cited for: STRUCTURE BY NMR OF 51-101.
  27. "Genetic alterations of the tumor suppressor gene WWOX in esophageal squamous cell carcinoma."
    Kuroki T., Trapasso F., Shiraishi T., Alder H., Mimori K., Mori M., Croce C.M.
    Cancer Res. 62:2258-2260(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT PRO-291.
  28. "The tumour suppressor gene WWOX is mutated in autosomal recessive cerebellar ataxia with epilepsy and mental retardation."
    Mallaret M., Synofzik M., Lee J., Sagum C.A., Mahajnah M., Sharkia R., Drouot N., Renaud M., Klein F.A., Anheim M., Tranchant C., Mignot C., Mandel J.L., Bedford M., Bauer P., Salih M.A., Schuele R., Schoels L., Aldaz C.M., Koenig M.
    Brain 137:411-419(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS SCAR12 THR-47 AND ARG-372.

Entry informationi

Entry nameiWWOX_HUMAN
AccessioniPrimary (citable) accession number: Q9NZC7
Secondary accession number(s): A8K323
, Q5MYT5, Q96KM3, Q96RF2, Q9BTT8, Q9NPC9, Q9NRF4, Q9NRF5, Q9NRF6, Q9NRK1, Q9NZC5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 22, 2005
Last sequence update: October 1, 2000
Last modified: November 26, 2014
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3