UniProt Accession

 WWOX_HUMAN; Q9NZC7; A8K323; Q5MYT5; Q96KM3; Q96RF2; Q9BTT8; Q9NPC9; Q9NRF4; Q9NRF5; Q9NRF6; Q9NRK1; Q9NZC5 

Genbank Protein ID

 AF211943; AF212843; AH009490; AF227526; AF227527; AF227528; AF227529; AF395123; AF395124; AF325432; AF325423; AF325424; AF325425; AF325426; AF325427; AF325428; AF325430; AF325431; AF325429; AF325423; AF325424; AF325425; AF325426; AF325427; AF325432; AF325423; AF325424; AF325425; AF325426; AF325433; AY256821; AK290438; BT007445; BC003184 

Genbank Nucleotide ID

 AAF27049.1; AAF27050.1; AAF78197.1; AAF82053.1; AAF82054.1; AAF82055.1; AAF82056.1; AAK81727.1; AAK81728.1; AAL05449.1; AAL05449.1; AAL05449.1; AAL05449.1; AAL05449.1; AAL05449.1; AAL05449.1; AAL05449.1; AAL05449.1; AAL05450.1; AAL05450.1; AAL05450.1; AAL05450.1; AAL05450.1; AAL05450.1; AAL05451.1; AAL05451.1; AAL05451.1; AAL05451.1; AAL05451.1; AAL05451.1; AAP94227.1; BAF83127.1; AAP36113.1; AAH03184.1 

Protein Name

 WW domain-containing oxidoreductase 

Protein Synonyms/Alias

 Fragile site FRA16D oxidoreductase 

Gene Name

 WWOX 

Gene Synonyms/Alias

 FOR; WOX1 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
28	GWEERTTKDGWVYYA	ubiquitination	[1]
100	TVDDNPTKPTTRQRY	ubiquitination	[1, 2]
176	LEEWHKAKVEAMTLD	ubiquitination	[1]
274	DINDSLGKLDFSRLS	ubiquitination	[1, 2, 3, 4]
284	FSRLSPTKNDYWAML	ubiquitination	[1]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [4] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 16 49 WW 1.
 DOMAIN 57 90 WW 2.
 NP_BIND 131 137 NADP (By similarity).
 REGION 125 414 Interaction with MAPT (By similarity).
 REGION 209 273 Mediates targeting to the mitochondria
 MOTIF 50 55 Nuclear localization signal (By
 ACT_SITE 293 293 Proton acceptor (By similarity).
 BINDING 260 260 Substrate (By similarity).
 MOD_RES 12 12 Phosphothreonine.
 MOD_RES 14 14 Phosphoserine.
 MOD_RES 33 33 Phosphotyrosine.
 MOD_RES 287 287 Phosphotyrosine; by TNK2.  

Keyword

 3D-structure; Alternative splicing; Apoptosis; Complete proteome; Cytoplasm; Disease mutation; Golgi apparatus; Mitochondrion; NADP; Nucleus; Oxidoreductase; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Tumor suppressor; Ubl conjugation; Wnt signaling pathway. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 414 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; IDA:BHF-UCL.
 GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
 GO:0005739; C:mitochondrion; ISS:BHF-UCL.
 GO:0005634; C:nucleus; IDA:BHF-UCL.
 GO:0050662; F:coenzyme binding; TAS:UniProtKB.
 GO:0016491; F:oxidoreductase activity; NAS:UniProtKB.
 GO:0046983; F:protein dimerization activity; TAS:UniProtKB.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:BHF-UCL.
 GO:0006917; P:induction of apoptosis; IEA:Compara.
 GO:0030178; P:negative regulation of Wnt receptor signaling pathway; IDA:UniProtKB.
 GO:0001649; P:osteoblast differentiation; IEA:Compara.
 GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; ISS:BHF-UCL.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISS:BHF-UCL.
 GO:0048705; P:skeletal system morphogenesis; ISS:BHF-UCL.
 GO:0008202; P:steroid metabolic process; TAS:UniProtKB.
 GO:0016055; P:Wnt receptor signaling pathway; IEA:UniProtKB-KW. 

Interpro

 IPR002198; DH_sc/Rdtase_SDR.
 IPR002347; Glc/ribitol_DH.
 IPR016040; NAD(P)-bd_dom.
 IPR001202; WW_dom. 

Pfam

 PF00106; adh_short
 PF00397; WW 

SMART

 SM00456; WW 

PROSITE

 PS00061; ADH_SHORT
 PS01159; WW_DOMAIN_1
 PS50020; WW_DOMAIN_2 

PRINTS

 PR00081; GDHRDH.