Q9NZC7 (WWOX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
WW domain-containing oxidoreductase
EC=1.1.1.-

Alternative name(s):
Fragile site FRA16D oxidoreductase

Gene names

Name:	WWOX
Synonyms:	FOR, WOX1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	414 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Apoptosis Wnt signaling pathway
Cellular component	Cytoplasm Golgi apparatus Mitochondrion Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Tumor suppressor
Domain	Repeat
Ligand	NADP
Molecular function	Oxidoreductase
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cellular response to transforming growth factor beta stimulus Inferred from direct assay Ref.21. Source: BHF-UCL induction of apoptosis Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of Wnt receptor signaling pathway Inferred from direct assay Ref.22. Source: UniProtKB osteoblast differentiation Inferred from electronic annotation. Source: Compara 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_component	Golgi apparatus Inferred from direct assay Ref.15. 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_function	coenzyme binding Traceable author statement Ref.1. Source: UniProtKB nucleotide binding Inferred from electronic annotation. Source: InterPro 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

With	Entry	#Exp.	IntAct	Notes
Erbb4	Q61527	3	EBI-4320739,EBI-4398741	From a different organism.
FAM189B	P81408	2	EBI-4320739,EBI-6366314
LITAF	Q99732	5	EBI-4320739,EBI-725647
SHISA5	Q8N114	2	EBI-4320739,EBI-2115556
WBP1	Q96G27	3	EBI-4320739,EBI-3867685

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 414

414

WW domain-containing oxidoreductase

PRO_0000054815

Regions

Domain

16 – 49

34

WW 1

Domain

57 – 90

34

WW 2

Nucleotide binding

131 – 137

7

NADP By similarity

Region

125 – 414

290

Interaction with MAPT By similarity

Region

209 – 273

65

Mediates targeting to the mitochondria By similarity

Motif

50 – 55

6

Nuclear localization signal By similarity

Sites

Active site

293

1

Proton acceptor By similarity

Binding site

260

1

Substrate By similarity

Amino acid modifications

Modified residue

12

1

Phosphothreonine Ref.23

Modified residue

14

1

Phosphoserine Ref.23

Modified residue

33

1

Phosphotyrosine Ref.16 Ref.21

Modified residue

287

1

Phosphotyrosine; by TNK2 Ref.18

Natural variations

Alternative sequence

36

1

N → K in isoform 4.

VSP_016358

Alternative sequence

37 – 414

378

Missing in isoform 4.

VSP_016359

Alternative sequence

137 – 414

278

GFETA…GSQSG → ATGSCHHRVLCCCPRTGGSG RDVLQQLLPLHALTRSSERR DGPDPVGAQREADPRTAWQP VRLSGAQSGWAHTPALCVSP HASARAGPLPNVPPTQIRKS KGNKSSHNRVKNLKYQWEAG NSWGKVSLFWGWARHRSLCF LVVACLKVKTCLVCRFRISL EKHQQFSFFYCYRIA in isoform 6.

VSP_016360

Alternative sequence

138 – 213

76

FETAK…CNAAT → KASCHVGRTLKHTRVEELSL LPTAINRELPPPCTVLLSQN WRVWEGCTSTTAAAACPHQK LRAKRRPGPCGRSARG in isoform 7.

VSP_016362

Alternative sequence

173 – 352

180

Missing in isoform 5.

VSP_016363

Alternative sequence

173 – 189

17

HKAKV…ALLRS → KTKYHPPPEKCRIKIFH in isoform 3.

VSP_016364

Alternative sequence

190 – 414

225

Missing in isoform 3.

VSP_016365

Alternative sequence

214 – 414

201

Missing in isoform 7.

VSP_016366

Alternative sequence

353 – 363

11

QQGAATTVYCA → VSDCLVEGGHF in isoform 2.

VSP_016367

Alternative sequence

364 – 414

51

Missing in isoform 2.

VSP_016369

Natural variant

98

1

P → L. Ref.4

VAR_023916

Natural variant

111

1

T → S in a Burkitt lymphoma cell line. Ref.4

VAR_023917

Natural variant

120

1

R → W in a primary colorectal tumor and a histiocytic lymphoma cell line. Ref.4

VAR_023918

Natural variant

179

1

A → T. Ref.4 Ref.5
Corresponds to variant rs12918952 [ dbSNP | Ensembl ].

VAR_023919

Natural variant

216

1

L → V.
Corresponds to variant rs7201683 [ dbSNP | Ensembl ].

VAR_052323

Natural variant

272

1

L → F. Ref.4

VAR_023920

Natural variant

282

1

P → A. Ref.4
Corresponds to variant rs3764340 [ dbSNP | Ensembl ].

VAR_023921

Natural variant

291

1

L → P Found in a esophageal cancer sample; somatic mutation. Ref.26

VAR_023922

Natural variant

314

1

R → H in a cervical carcinoma cell line. Ref.4

VAR_023923

Isoform 3:

Natural variant

182

1

K → E Found in a primary colorectal tumor and tumor cells.

Experimental info

Mutagenesis

28

1

K → T: No effect on interaction with TP53. Abolishes interaction with MAPK8; when associated with V-29. Ref.10

Mutagenesis

29

1

D → V: No effect on interaction with TP53. Abolishes interaction with MAPK8; when associated with T-28. Ref.10

Mutagenesis

33

1

Y → F: Loss of phosphorylation. Ref.10 Ref.16

Mutagenesis

33

1

Y → 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

Mutagenesis

44 – 47

4

WEHP → FEHA: Abolishes interaction with LITAF. Ref.15

Mutagenesis

61

1

Y → R: No effect on interaction with TP73. Ref.16

Mutagenesis

85 – 88

4

YLDP → ALDA: No effect on interaction with LITAF. Ref.15

Mutagenesis

287

1

Y → A: Loss of phosphorylation by TNK2. Ref.18

Secondary structure

1

.

.

.

.

.

.

.

414

Helix Strand Turn

Details...

Beta strand

63 – 67

5

Beta strand

73 – 80

8

Beta strand

83 – 86

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (FOR II) (FOR2) (WWOXv1) (WWOX v8) [UniParc]. Last modified October 1, 2000. Version 1. Checksum: E4D9A649E6CB05DF	FASTA	414	46,677
	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
	Isoform 2 (FOR I) (FOR1) (WOX2) (WWOXv2) [UniParc]. Checksum: C1BB208B887281C3	FASTA	363	41,128
	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 SMVSDCLVEG GHF
	Isoform 3 (FOR III) (FOR3) (WOX3) [UniParc]. Checksum: 82155A9AD7C824C7	FASTA	189	21,559
	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 EWKTKYHPPP EKCRIKIFH
	Isoform 4 (FOR IV) [UniParc]. Checksum: A6D0FEE1CAE266B2	FASTA	36	4,150
	10 20 30 MAALRYAGLD DTDSEDELPP GWEERTTKDG WVYYAK
	Isoform 5 (WWOXdelta6-8) (WWOXv4) [UniParc]. Checksum: C69FB6B3E87635F4	FASTA	234	26,148
	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 EWQQGAATTV 190 200 210 220 230 YCAAVPELEG LGGMYFNNCC RCMPSPEAQS EETARTLWAL SERLIQERLG SQSG
	Isoform 6 (WWOXdelta5-8) (WWOXv3) [UniParc]. Checksum: 8EF6B9823F90C9F7	FASTA	311	35,042
	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 GANSGIATGS CHHRVLCCCP RTGGSGRDVL QQLLPLHALT RSSERRDGPD 190 200 210 220 230 240 PVGAQREADP RTAWQPVRLS GAQSGWAHTP ALCVSPHASA RAGPLPNVPP TQIRKSKGNK 250 260 270 280 290 300 SSHNRVKNLK YQWEAGNSWG KVSLFWGWAR HRSLCFLVVA CLKVKTCLVC RFRISLEKHQ 310 QFSFFYCYRI A
	Isoform 7 [UniParc]. Checksum: A21054FF8214CC7C	FASTA	213	23,868
	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 GANSGIGKAS CHVGRTLKHT RVEELSLLPT AINRELPPPC TVLLSQNWRV 190 200 210 WEGCTSTTAA AACPHQKLRA KRRPGPCGRS ARG

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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 , 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.

IPI

IPI00030484.
IPI00045224.
IPI00099822.
IPI00107757.
IPI00107869.
IPI00299802.
IPI00550494.

RefSeq

NP_057457.1. NM_016373.2.
NP_570607.1. NM_130791.2.
NP_570859.1. NM_130844.2.

UniGene

Hs.461453.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WMV	NMR	-	A	51-101	[»]

ProteinModelPortal

Q9NZC7.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NZC7. 6 interactions.

MINT

MINT-1175612.

PTM databases

PhosphoSite

Q9NZC7.

Polymorphism databases

DMDM

74725363.

Proteomic databases

PaxDb

Q9NZC7.

PRIDE

Q9NZC7.

Protocols and materials databases

DNASU

51741.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000355860; ENSP00000348119; ENSG00000186153.
ENST00000402655; ENSP00000384238; ENSG00000186153.
ENST00000406884; ENSP00000384495; ENSG00000186153.
ENST00000408984; ENSP00000386161; ENSG00000186153.
ENST00000566780; ENSP00000457230; ENSG00000186153.
ENST00000569818; ENSP00000454485; ENSG00000186153.

GeneID

51741.

KEGG

hsa:51741.

UCSC

uc002ffi.2. human.
uc002ffj.2. human.
uc002ffk.3. human.
uc002ffl.3. human.
uc010che.3. human.

Organism-specific databases

CTD

51741.

GeneCards

GC16P078133.

HGNC

HGNC:12799. WWOX.

MIM

133239. phenotype.
605131. gene.

neXtProt

NX_Q9NZC7.

Orphanet

251510. 46,XY partial gonadal dysgenesis.
99977. Esophageal squamous cell carcinoma.

PharmGKB

PA37398.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1028.

HOVERGEN

HBG078800.

OMA

YSNIHRS.

PhylomeDB

Q9NZC7.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

Q9NZC7.

Bgee

Q9NZC7.

Genevestigator

Q9NZC7.

Family and domain databases

Gene3D

3.40.50.720. 1 hit.

InterPro

IPR002198. DH_sc/Rdtase_SDR.
IPR002347. Glc/ribitol_DH.
IPR016040. NAD(P)-bd_dom.
IPR001202. WW_dom.
[Graphical view]

Pfam

PF00106. adh_short. 1 hit.
PF00397. WW. 2 hits.
[Graphical view]

PRINTS

PR00081. GDHRDH.

SMART

SM00456. WW. 2 hits.
[Graphical view]

SUPFAM

SSF51045. WW_Rsp5_WWP. 2 hits.

PROSITE

PS00061. ADH_SHORT. False negative.
PS01159. WW_DOMAIN_1. 2 hits.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

WWOX. human.

EvolutionaryTrace

Q9NZC7.

GenomeRNAi

51741.

NextBio

55812.

SOURCE

Search...

Entry information

Entry name

WWOX_HUMAN

Accession

Primary (citable) accession number: Q9NZC7
Secondary accession number(s): A8K323 , 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:	May 1, 2013
This is version 117 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.