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Q9NZC7 (WWOX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
WW domain-containing oxidoreductase

EC=1.1.1.-
Alternative name(s):
Fragile site FRA16D oxidoreductase
Gene names
Name:WWOX
Synonyms:FOR, WOX1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length414 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.3 Ref.12 Ref.16 Ref.17 Ref.19 Ref.21 Ref.22

Subunit structure

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. Ref.10 Ref.12 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.21 Ref.22 Ref.24

Subcellular location

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. Ref.9 Ref.15 Ref.16 Ref.19 Ref.21 Ref.22

Tissue specificity

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. Ref.1 Ref.3

Domain

The WW 1 domain mediates interaction with TP53, and probably TP73, TFAP2C, LITAF and WBP1. Ref.12 Ref.15 Ref.16

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. Ref.16 Ref.18 Ref.19 Ref.21

Ubiquitinated when phosphorylated by TNK2, leading to its degradation. Ref.16 Ref.18 Ref.19 Ref.21

Involvement in disease

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. Ref.4 Ref.11 Ref.13 Ref.14 Ref.20

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. Ref.4 Ref.11 Ref.13 Ref.14 Ref.20

Sequence similarities

Belongs to the short-chain dehydrogenases/reductases (SDR) family.

Contains 2 WW domains.

Sequence caution

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

Ontologies

Keywords
   Biological processApoptosis
Wnt signaling pathway
   Cellular componentCytoplasm
Golgi apparatus
Mitochondrion
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Tumor suppressor
   DomainRepeat
   LigandNADP
   Molecular functionOxidoreductase
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to transforming growth factor beta stimulus

Inferred from direct assay Ref.21. Source: BHF-UCL

extrinsic apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

intrinsic apoptotic signaling pathway by p53 class mediator

Inferred from electronic annotation. Source: Ensembl

negative regulation of Wnt signaling pathway

Inferred from direct assay Ref.22. Source: UniProtKB

osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

oxidation-reduction process

Traceable author statement Ref.1. Source: UniProtKB

positive regulation of extrinsic apoptotic signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of extrinsic apoptotic signaling pathway in absence of ligand

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: BHF-UCL

skeletal system morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

steroid metabolic process

Traceable author statement Ref.1. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from direct assay Ref.15. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.22. Source: UniProtKB

cytosol

Inferred from direct assay Ref.21. Source: BHF-UCL

mitochondrion

Inferred from sequence or structural similarity. Source: BHF-UCL

nucleus

Inferred from direct assay Ref.21. Source: BHF-UCL

   Molecular_functioncoenzyme binding

Traceable author statement Ref.1. Source: UniProtKB

cofactor binding

Traceable author statement Ref.1. Source: UniProtKB

enzyme binding

Inferred from physical interaction Ref.21. Source: BHF-UCL

oxidoreductase activity

Non-traceable author statement Ref.2. Source: UniProtKB

protein dimerization activity

Traceable author statement Ref.1. Source: UniProtKB

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NZC7-1)

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.
Isoform 2 (identifier: Q9NZC7-2)

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.
Isoform 3 (identifier: Q9NZC7-3)

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.
Isoform 4 (identifier: Q9NZC7-4)

Also known as: FOR IV;

The sequence of this isoform differs from the canonical sequence as follows:
     36-36: N → K
     37-414: Missing.
Isoform 5 (identifier: Q9NZC7-5)

Also known as: WWOXdelta6-8; WWOXv4;

The sequence of this isoform differs from the canonical sequence as follows:
     173-352: Missing.
Isoform 6 (identifier: Q9NZC7-6)

Also known as: WWOXdelta5-8; WWOXv3;

The sequence of this isoform differs from the canonical sequence as follows:
     137-414: GFETAKSFAL...IQERLGSQSG → ATGSCHHRVL...FSFFYCYRIA
Isoform 7 (identifier: Q9NZC7-7)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 414414WW domain-containing oxidoreductase
PRO_0000054815

Regions

Domain16 – 4934WW 1
Domain57 – 9034WW 2
Nucleotide binding131 – 1377NADP By similarity
Region125 – 414290Interaction with MAPT By similarity
Region209 – 27365Mediates targeting to the mitochondria By similarity
Motif50 – 556Nuclear localization signal By similarity

Sites

Active site2931Proton acceptor By similarity
Binding site2601Substrate By similarity

Amino acid modifications

Modified residue121Phosphothreonine Ref.23
Modified residue141Phosphoserine Ref.23
Modified residue331Phosphotyrosine Ref.16 Ref.21
Modified residue2871Phosphotyrosine; by TNK2 Ref.18

Natural variations

Alternative sequence361N → K in isoform 4.
VSP_016358
Alternative sequence37 – 414378Missing in isoform 4.
VSP_016359
Alternative sequence137 – 414278GFETA…GSQSG → ATGSCHHRVLCCCPRTGGSG RDVLQQLLPLHALTRSSERR DGPDPVGAQREADPRTAWQP VRLSGAQSGWAHTPALCVSP HASARAGPLPNVPPTQIRKS KGNKSSHNRVKNLKYQWEAG NSWGKVSLFWGWARHRSLCF LVVACLKVKTCLVCRFRISL EKHQQFSFFYCYRIA in isoform 6.
VSP_016360
Alternative sequence138 – 21376FETAK…CNAAT → KASCHVGRTLKHTRVEELSL LPTAINRELPPPCTVLLSQN WRVWEGCTSTTAAAACPHQK LRAKRRPGPCGRSARG in isoform 7.
VSP_016362
Alternative sequence173 – 352180Missing in isoform 5.
VSP_016363
Alternative sequence173 – 18917HKAKV…ALLRS → KTKYHPPPEKCRIKIFH in isoform 3.
VSP_016364
Alternative sequence190 – 414225Missing in isoform 3.
VSP_016365
Alternative sequence214 – 414201Missing in isoform 7.
VSP_016366
Alternative sequence353 – 36311QQGAATTVYCA → VSDCLVEGGHF in isoform 2.
VSP_016367
Alternative sequence364 – 41451Missing in isoform 2.
VSP_016369
Natural variant981P → L. Ref.4
Corresponds to variant rs144601717 [ dbSNP | Ensembl ].
VAR_023916
Natural variant1111T → S in a Burkitt lymphoma cell line. Ref.4
Corresponds to variant rs114755364 [ dbSNP | Ensembl ].
VAR_023917
Natural variant1201R → W in a primary colorectal tumor and a histiocytic lymphoma cell line. Ref.4
Corresponds to variant rs141361080 [ dbSNP | Ensembl ].
VAR_023918
Natural variant1791A → T. Ref.4 Ref.5
Corresponds to variant rs12918952 [ dbSNP | Ensembl ].
VAR_023919
Natural variant2161L → V.
Corresponds to variant rs7201683 [ dbSNP | Ensembl ].
VAR_052323
Natural variant2721L → F. Ref.4
Corresponds to variant rs186745328 [ dbSNP | Ensembl ].
VAR_023920
Natural variant2821P → A. Ref.4
Corresponds to variant rs3764340 [ dbSNP | Ensembl ].
VAR_023921
Natural variant2911L → P Found in a esophageal cancer sample; somatic mutation. Ref.26
VAR_023922
Natural variant3141R → H in a cervical carcinoma cell line. Ref.4
Corresponds to variant rs73572838 [ dbSNP | Ensembl ].
VAR_023923
Isoform 3:
Natural variant1821K → E Found in a primary colorectal tumor and tumor cells.

Experimental info

Mutagenesis281K → T: No effect on interaction with TP53. Abolishes interaction with MAPK8; when associated with V-29. Ref.10
Mutagenesis291D → V: No effect on interaction with TP53. Abolishes interaction with MAPK8; when associated with T-28. Ref.10
Mutagenesis331Y → F: Loss of phosphorylation. Ref.10 Ref.16
Mutagenesis331Y → R: Abolishes interaction with TP53, TP73, MAPK8 and ERBB4. Partial loss of interaction with TFAP2C. Loss of phosphorylation. Loss of the proapoptotic activity. Ref.10 Ref.16
Mutagenesis44 – 474WEHP → FEHA: Abolishes interaction with LITAF. Ref.15
Mutagenesis611Y → R: No effect on interaction with TP73. Ref.16
Mutagenesis85 – 884YLDP → ALDA: No effect on interaction with LITAF. Ref.15
Mutagenesis2871Y → A: Loss of phosphorylation by TNK2. Ref.18

Secondary structure

....... 414
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (FOR II) (FOR2) (WWOXv1) (WWOX v8) [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: E4D9A649E6CB05DF

FASTA41446,677
        10         20         30         40         50         60 
MAALRYAGLD DTDSEDELPP GWEERTTKDG WVYYANHTEE KTQWEHPKTG KRKRVAGDLP 

        70         80         90        100        110        120 
YGWEQETDEN GQVFFVDHIN KRTTYLDPRL AFTVDDNPTK PTTRQRYDGS TTAMEILQGR 

       130        140        150        160        170        180 
DFTGKVVVVT GANSGIGFET AKSFALHGAH VILACRNMAR ASEAVSRILE EWHKAKVEAM 

       190        200        210        220        230        240 
TLDLALLRSV QHFAEAFKAK NVPLHVLVCN AATFALPWSL TKDGLETTFQ VNHLGHFYLV 

       250        260        270        280        290        300 
QLLQDVLCRS APARVIVVSS ESHRFTDIND SLGKLDFSRL SPTKNDYWAM LAYNRSKLCN 

       310        320        330        340        350        360 
ILFSNELHRR LSPRGVTSNA VHPGNMMYSN IHRSWWVYTL LFTLARPFTK SMQQGAATTV 

       370        380        390        400        410 
YCAAVPELEG LGGMYFNNCC RCMPSPEAQS EETARTLWAL SERLIQERLG SQSG 

« Hide

Isoform 2 (FOR I) (FOR1) (WOX2) (WWOXv2) [UniParc].

Checksum: C1BB208B887281C3
Show »

FASTA36341,128
Isoform 3 (FOR III) (FOR3) (WOX3) [UniParc].

Checksum: 82155A9AD7C824C7
Show »

FASTA18921,559
Isoform 4 (FOR IV) [UniParc].

Checksum: A6D0FEE1CAE266B2
Show »

FASTA364,150
Isoform 5 (WWOXdelta6-8) (WWOXv4) [UniParc].

Checksum: C69FB6B3E87635F4
Show »

FASTA23426,148
Isoform 6 (WWOXdelta5-8) (WWOXv3) [UniParc].

Checksum: 8EF6B9823F90C9F7
Show »

FASTA31135,042
Isoform 7 [UniParc].

Checksum: A21054FF8214CC7C
Show »

FASTA21323,868

References

« Hide 'large scale' references
[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]"WWOX: a candidate tumor suppressor gene involved in multiple tumor types."
Paige A.J.W., Taylor K.J., Taylor C., Hillier S.G., Farrington S., Scott D., Porteous D.J., Smyth J.F., Gabra H., Watson J.E.V.
Proc. Natl. Acad. Sci. U.S.A. 98:11417-11422(2001) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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]"The tumor suppressor gene WWOX at FRA16D is involved in pancreatic carcinogenesis."
Kuroki T., Yendamuri S., Trapasso F., Matsuyama A., Aqeilan R.I., Alder H., Rattan S., Cesari R., Nolli M.L., Williams N.N., Mori M., Kanematsu T., Croce C.M.
Clin. Cancer Res. 10:2459-2465(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: DISEASE.
[14]"Loss of WWOX expression in gastric carcinoma."
Aqeilan R.I., Kuroki T., Pekarsky Y., Albagha O., Trapasso F., Baffa R., Huebner K., Edmonds P., Croce C.M.
Clin. Cancer Res. 10:3053-3058(2004) [PubMed] [Europe PMC] [Abstract]
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]"Functional association between Wwox tumor suppressor protein and p73, a p53 homolog."
Aqeilan R.I., Pekarsky Y., Herrero J.J., Palamarchuk A., Letofsky J., Druck T., Trapasso F., Han S.-Y., Melino G., Huebner K., Croce C.M.
Proc. Natl. Acad. Sci. U.S.A. 101:4401-4406(2004) [PubMed] [Europe PMC] [Abstract]
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]"WWOX gene restoration prevents lung cancer growth in vitro and in vivo."
Fabbri M., Iliopoulos D., Trapasso F., Aqeilan R.I., Cimmino A., Zanesi N., Yendamuri S., Han S.-Y., Amadori D., Huebner K., Croce C.M.
Proc. Natl. Acad. Sci. U.S.A. 102:15611-15616(2005) [PubMed] [Europe PMC] [Abstract]
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]"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.
[26]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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 expand/collapse EMBL AC list , AF325423, AF325424, AF325425, AF325426, AF325427, AF325428, AF325430, AF325431 Genomic DNA. Translation: AAL05449.1.
AF325429 expand/collapse EMBL AC list , AF325423, AF325424, AF325425, AF325426, AF325427 Genomic DNA. Translation: AAL05450.1.
AF325432 expand/collapse EMBL AC list , 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.
RefSeqNP_057457.1. NM_016373.2.
NP_570607.1. NM_130791.2.
NP_570859.1. NM_130844.2.
UniGeneHs.461453.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1WMVNMR-A51-101[»]
ProteinModelPortalQ9NZC7.
SMRQ9NZC7. Positions 13-101, 121-407.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119707. 30 interactions.
IntActQ9NZC7. 6 interactions.
MINTMINT-1175612.

PTM databases

PhosphoSiteQ9NZC7.

Polymorphism databases

DMDM74725363.

Proteomic databases

PaxDbQ9NZC7.
PRIDEQ9NZC7.

Protocols and materials databases

DNASU51741.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000355860; 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]
GeneID51741.
KEGGhsa:51741.
UCSCuc002ffi.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

CTD51741.
GeneCardsGC16P078133.
HGNCHGNC:12799. WWOX.
HPAHPA050992.
MIM133239. phenotype.
605131. gene.
neXtProtNX_Q9NZC7.
Orphanet251510. 46,XY partial gonadal dysgenesis.
PharmGKBPA37398.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1028.
HOVERGENHBG078800.
OMAYSNIHRS.
OrthoDBEOG73Z2TK.
PhylomeDBQ9NZC7.
TreeFamTF105428.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkQ9NZC7.

Gene expression databases

ArrayExpressQ9NZC7.
BgeeQ9NZC7.
GenevestigatorQ9NZC7.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
InterProIPR002198. DH_sc/Rdtase_SDR.
IPR002347. Glc/ribitol_DH.
IPR016040. NAD(P)-bd_dom.
IPR001202. WW_dom.
[Graphical view]
PfamPF00106. adh_short. 1 hit.
PF00397. WW. 2 hits.
[Graphical view]
PRINTSPR00081. GDHRDH.
SMARTSM00456. WW. 2 hits.
[Graphical view]
SUPFAMSSF51045. SSF51045. 2 hits.
PROSITEPS01159. WW_DOMAIN_1. 2 hits.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSWWOX. human.
EvolutionaryTraceQ9NZC7.
GeneWikiWWOX.
GenomeRNAi51741.
NextBio55812.
PROQ9NZC7.
SOURCESearch...

Entry information

Entry nameWWOX_HUMAN
AccessionPrimary (citable) accession number: Q9NZC7
Secondary accession number(s): A8K323 expand/collapse secondary AC list , Q5MYT5, Q96KM3, Q96RF2, Q9BTT8, Q9NPC9, Q9NRF4, Q9NRF5, Q9NRF6, Q9NRK1, Q9NZC5
Entry history
Integrated into UniProtKB/Swiss-Prot: November 22, 2005
Last sequence update: October 1, 2000
Last modified: April 16, 2014
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM