WWOX_HUMAN
ID WWOX_HUMAN Reviewed; 414 AA.
AC Q9NZC7; A8K323; Q5MYT5; Q96KM3; Q96RF2; Q9BTT8; Q9NPC9; Q9NRF4; Q9NRF5;
AC Q9NRF6; Q9NRK1; Q9NZC5;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=WW domain-containing oxidoreductase;
DE EC=1.1.1.-;
DE AltName: Full=Fragile site FRA16D oxidoreductase;
DE AltName: Full=Short chain dehydrogenase/reductase family 41C member 1;
GN Name=WWOX; Synonyms=FOR, SDR41C1, WOX1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [GENOMIC DNA]
RP OF 1-35, AND TISSUE SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=10786676;
RA Bednarek A.K., Laflin K.J., Daniel R.L., Liao Q., Hawkins K.A., Aldaz C.M.;
RT "WWOX, a novel WW domain-containing protein mapping to human chromosome
RT 16q23.3-24.1, a region frequently affected in breast cancer.";
RL Cancer Res. 60:2140-2145(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), NUCLEOTIDE SEQUENCE
RP [GENOMIC DNA] OF 173-414, AND CHROMOSOMAL REARRANGEMENT.
RX PubMed=10861292; DOI=10.1093/hmg/9.11.1651;
RA Ried K., Finnis M., Hobson L., Mangelsdorf M., Dayan S., Nancarrow J.K.,
RA Woollatt E., Kremmidiotis G., Gardner A., Venter D., Baker E.,
RA Richards R.I.;
RT "Common chromosomal fragile site FRA16D sequence: identification of the FOR
RT gene spanning FRA16D and homozygous deletions and translocation breakpoints
RT in cancer cells.";
RL Hum. Mol. Genet. 9:1651-1663(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5 AND 6), FUNCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=11719429;
RA Bednarek A.K., Keck-Waggoner C.L., Daniel R.L., Laflin K.J.,
RA Bergsagel P.L., Kiguchi K., Brenner A.J., Aldaz C.M.;
RT "WWOX, the FRA16D gene, behaves as a suppressor of tumor growth.";
RL Cancer Res. 61:8068-8073(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS 1; 3 AND
RP 7), VARIANTS LEU-98; SER-111; TRP-120; THR-179; PHE-272; ALA-282 AND
RP HIS-314, AND INVOLVEMENT IN CANCERS.
RX PubMed=11572989; DOI=10.1073/pnas.191175898;
RA Paige A.J.W., Taylor K.J., Taylor C., Hillier S.G., Farrington S.,
RA Scott D., Porteous D.J., Smyth J.F., Gabra H., Watson J.E.V.;
RT "WWOX: a candidate tumor suppressor gene involved in multiple tumor
RT types.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:11417-11422(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT THR-179.
RC TISSUE=Colon adenocarcinoma;
RA Chang N.-S.;
RT "Cloning of human WOX8 (WWOX v8).";
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=14695174;
RA Watanabe A., Hippo Y., Taniguchi H., Iwanari H., Yashiro M., Hirakawa K.,
RA Kodama T., Aburatani H.;
RT "An opposing view on WWOX protein function as a tumor suppressor.";
RL Cancer Res. 63:8629-8633(2003).
RN [10]
RP INTERACTION WITH MAPK8 AND TP53, AND MUTAGENESIS OF LYS-28; ASP-29 AND
RP TYR-33.
RX PubMed=12514174; DOI=10.1074/jbc.m208373200;
RA Chang N.-S., Doherty J., Ensign A.;
RT "JNK1 physically interacts with WW domain-containing oxidoreductase (WOX1)
RT and inhibits WOX1-mediated apoptosis.";
RL J. Biol. Chem. 278:9195-9202(2003).
RN [11]
RP INVOLVEMENT IN CANCERS.
RX PubMed=15266310; DOI=10.1038/sj.bjc.6602023;
RA Park S.-W., Ludes-Meyers J., Zimonjic D.B., Durkin M.E., Popescu N.C.,
RA Aldaz C.M.;
RT "Frequent downregulation and loss of WWOX gene expression in human
RT hepatocellular carcinoma.";
RL Br. J. Cancer 91:753-759(2004).
RN [12]
RP FUNCTION, INTERACTION WITH TFAP2C AND TFAP2A, AND DOMAIN.
RX PubMed=15548692; DOI=10.1158/0008-5472.can-04-2055;
RA Aqeilan R.I., Palamarchuk A., Weigel R.J., Herrero J.J., Pekarsky Y.,
RA Croce C.M.;
RT "Physical and functional interactions between the Wwox tumor suppressor
RT protein and the AP-2gamma transcription factor.";
RL Cancer Res. 64:8256-8261(2004).
RN [13]
RP INVOLVEMENT IN CANCERS.
RX PubMed=15073125; DOI=10.1158/1078-0432.ccr-03-0096;
RA Kuroki T., Yendamuri S., Trapasso F., Matsuyama A., Aqeilan R.I., Alder H.,
RA Rattan S., Cesari R., Nolli M.L., Williams N.N., Mori M., Kanematsu T.,
RA Croce C.M.;
RT "The tumor suppressor gene WWOX at FRA16D is involved in pancreatic
RT carcinogenesis.";
RL Clin. Cancer Res. 10:2459-2465(2004).
RN [14]
RP INVOLVEMENT IN CANCERS.
RX PubMed=15131042; DOI=10.1158/1078-0432.ccr-03-0594;
RA Aqeilan R.I., Kuroki T., Pekarsky Y., Albagha O., Trapasso F., Baffa R.,
RA Huebner K., Edmonds P., Croce C.M.;
RT "Loss of WWOX expression in gastric carcinoma.";
RL Clin. Cancer Res. 10:3053-3058(2004).
RN [15]
RP INTERACTION WITH LITAF; WBP1; FAM189B AND SCOTIN, MUTAGENESIS OF
RP 44-TRP--PRO-47 AND 85-TYR--PRO-88, DOMAIN, AND SUBCELLULAR LOCATION.
RX PubMed=15064722; DOI=10.1038/sj.onc.1207680;
RA Ludes-Meyers J.H., Kil H., Bednarek A.K., Drake J., Bedford M.T.,
RA Aldaz C.M.;
RT "WWOX binds the specific proline-rich ligand PPXY: identification of
RT candidate interacting proteins.";
RL Oncogene 23:5049-5055(2004).
RN [16]
RP FUNCTION, INTERACTION WITH TP73, DOMAIN, MUTAGENESIS OF TYR-33 AND TYR-61,
RP PHOSPHORYLATION AT TYR-33, AND SUBCELLULAR LOCATION.
RX PubMed=15070730; DOI=10.1073/pnas.0400805101;
RA Aqeilan R.I., Pekarsky Y., Herrero J.J., Palamarchuk A., Letofsky J.,
RA Druck T., Trapasso F., Han S.-Y., Melino G., Huebner K., Croce C.M.;
RT "Functional association between Wwox tumor suppressor protein and p73, a
RT p53 homolog.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:4401-4406(2004).
RN [17]
RP FUNCTION, AND INTERACTION WITH ERBB4.
RX PubMed=16061658; DOI=10.1158/0008-5472.can-05-1150;
RA Aqeilan R.I., Donati V., Palamarchuk A., Trapasso F., Kaou M., Pekarsky Y.,
RA Sudol M., Croce C.M.;
RT "WW domain-containing proteins, WWOX and YAP, compete for interaction with
RT ErbB-4 and modulate its transcriptional function.";
RL Cancer Res. 65:6764-6772(2005).
RN [18]
RP PHOSPHORYLATION AT TYR-287 BY TNK2, UBIQUITINATION, MUTAGENESIS OF TYR-287,
RP AND INTERACTION WITH TNK2.
RX PubMed=16288044; DOI=10.1158/0008-5472.can-05-1127;
RA Mahajan N.P., Whang Y.E., Mohler J.L., Earp H.S.;
RT "Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of
RT Ack1 in polyubiquitination of tumor suppressor Wwox.";
RL Cancer Res. 65:10514-10523(2005).
RN [19]
RP FUNCTION, INTERACTION WITH MDM2 AND TP53, PHOSPHORYLATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=16219768; DOI=10.1074/jbc.m505590200;
RA Chang N.-S., Doherty J., Ensign A., Schultz L., Hsu L.-J., Hong Q.;
RT "WOX1 is essential for tumor necrosis factor-, UV light-, staurosporine-,
RT and p53-mediated cell death, and its tyrosine 33-phosphorylated form binds
RT and stabilizes serine 46-phosphorylated p53.";
RL J. Biol. Chem. 280:43100-43108(2005).
RN [20]
RP DISEASE.
RX PubMed=16223882; DOI=10.1073/pnas.0505485102;
RA Fabbri M., Iliopoulos D., Trapasso F., Aqeilan R.I., Cimmino A., Zanesi N.,
RA Yendamuri S., Han S.-Y., Amadori D., Huebner K., Croce C.M.;
RT "WWOX gene restoration prevents lung cancer growth in vitro and in vivo.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:15611-15616(2005).
RN [21]
RP FUNCTION, PHOSPHORYLATION AT TYR-33, SUBCELLULAR LOCATION, AND INTERACTION
RP WITH HYAL2.
RX PubMed=19366691; DOI=10.1074/jbc.m806688200;
RA Hsu L.-J., Schultz L., Hong Q., Van Moer K., Heath J., Li M.-Y., Lai F.-J.,
RA Lin S.-R., Lee M.-H., Lo C.-P., Lin Y.-S., Chen S.-T., Chang N.-S.;
RT "Transforming growth factor beta1 signaling via interaction with cell
RT surface Hyal-2 and recruitment of WWOX/WOX1.";
RL J. Biol. Chem. 284:16049-16059(2009).
RN [22]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH DVL1; DVL2 AND DVL3.
RX PubMed=19465938; DOI=10.1038/onc.2009.120;
RA Bouteille N., Driouch K., Hage P.E., Sin S., Formstecher E., Camonis J.,
RA Lidereau R., Lallemand F.;
RT "Inhibition of the Wnt/beta-catenin pathway by the WWOX tumor suppressor
RT protein.";
RL Oncogene 28:2569-2580(2009).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-12 AND SER-14, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [24]
RP INTERACTION WITH TMEM207.
RX PubMed=22226915; DOI=10.1093/carcin/bgs001;
RA Takeuchi T., Adachi Y., Nagayama T.;
RT "A WWOX-binding molecule, transmembrane protein 207, is related to the
RT invasiveness of gastric signet-ring cell carcinoma.";
RL Carcinogenesis 33:548-554(2012).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [26]
RP INVOLVEMENT IN SCAR12.
RX PubMed=24456803; DOI=10.1186/1750-1172-9-12;
RA Abdel-Salam G., Thoenes M., Afifi H.H., Koerber F., Swan D., Bolz H.J.;
RT "The supposed tumor suppressor gene WWOX is mutated in an early lethal
RT microcephaly syndrome with epilepsy, growth retardation and retinal
RT degeneration.";
RL Orphanet J. Rare Dis. 9:12-12(2014).
RN [27]
RP INVOLVEMENT IN DEE28, AND VARIANT DEE28 ARG-47.
RX PubMed=25411445; DOI=10.1136/jmedgenet-2014-102748;
RA Mignot C., Lambert L., Pasquier L., Bienvenu T., Delahaye-Duriez A.,
RA Keren B., Lefranc J., Saunier A., Allou L., Roth V., Valduga M.,
RA Moustaine A., Auvin S., Barrey C., Chantot-Bastaraud S., Lebrun N.,
RA Moutard M.L., Nougues M.C., Vermersch A.I., Heron B., Pipiras E., Heron D.,
RA Olivier-Faivre L., Gueant J.L., Jonveaux P., Philippe C.;
RT "WWOX-related encephalopathies: delineation of the phenotypical spectrum
RT and emerging genotype-phenotype correlation.";
RL J. Med. Genet. 52:61-70(2015).
RN [28]
RP STRUCTURE BY NMR OF 51-101.
RA Kowalski K., Merkel A.L., Colella A., Richards R.I., Booker G.W.;
RT "Solution structure of the second WW domain of WWOX.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [29]
RP VARIANT PRO-291, AND INVOLVEMENT IN ESCR.
RX PubMed=11956080;
RA Kuroki T., Trapasso F., Shiraishi T., Alder H., Mimori K., Mori M.,
RA Croce C.M.;
RT "Genetic alterations of the tumor suppressor gene WWOX in esophageal
RT squamous cell carcinoma.";
RL Cancer Res. 62:2258-2260(2002).
RN [30]
RP VARIANTS SCAR12 THR-47 AND ARG-372.
RX PubMed=24369382; DOI=10.1093/brain/awt338;
RA Mallaret M., Synofzik M., Lee J., Sagum C.A., Mahajnah M., Sharkia R.,
RA Drouot N., Renaud M., Klein F.A., Anheim M., Tranchant C., Mignot C.,
RA Mandel J.L., Bedford M., Bauer P., Salih M.A., Schuele R., Schoels L.,
RA Aldaz C.M., Koenig M.;
RT "The tumour suppressor gene WWOX is mutated in autosomal recessive
RT cerebellar ataxia with epilepsy and mental retardation.";
RL Brain 137:411-419(2014).
CC -!- FUNCTION: Putative oxidoreductase. Acts as a tumor suppressor and plays
CC a role in apoptosis. Required for normal bone development (By
CC similarity). May function synergistically with p53/TP53 to control
CC genotoxic stress-induced cell death. Plays a role in TGFB1 signaling
CC and TGFB1-mediated cell death. May also play a role in tumor necrosis
CC factor (TNF)-mediated cell death. Inhibits Wnt signaling, probably by
CC sequestering DVL2 in the cytoplasm. {ECO:0000250,
CC ECO:0000269|PubMed:11719429, ECO:0000269|PubMed:15070730,
CC ECO:0000269|PubMed:15548692, ECO:0000269|PubMed:16061658,
CC ECO:0000269|PubMed:16219768, ECO:0000269|PubMed:19366691,
CC ECO:0000269|PubMed:19465938}.
CC -!- SUBUNIT: Interacts with TP53, p73/TP73 and MAPK8. Interacts with
CC MAPT/TAU, RUNX2 and HYAL2 (By similarity). Forms a ternary complex with
CC TP53 and MDM2. Interacts with ERBB4, LITAF and WBP1. Interacts with
CC DVL1, DVL2 and DVL3. May interact with FAM189B and SCOTIN. Interacts
CC with TNK2. Interacts with TMEM207. {ECO:0000250,
CC ECO:0000269|PubMed:12514174, ECO:0000269|PubMed:15064722,
CC ECO:0000269|PubMed:15070730, ECO:0000269|PubMed:15548692,
CC ECO:0000269|PubMed:16061658, ECO:0000269|PubMed:16219768,
CC ECO:0000269|PubMed:16288044, ECO:0000269|PubMed:19366691,
CC ECO:0000269|PubMed:19465938, ECO:0000269|PubMed:22226915}.
CC -!- INTERACTION:
CC Q9NZC7; P81408: FAM189B; NbExp=2; IntAct=EBI-4320739, EBI-6366314;
CC Q9NZC7; Q99732: LITAF; NbExp=5; IntAct=EBI-4320739, EBI-725647;
CC Q9NZC7; Q8N114: SHISA5; NbExp=2; IntAct=EBI-4320739, EBI-2115556;
CC Q9NZC7; P04637: TP53; NbExp=2; IntAct=EBI-4320739, EBI-366083;
CC Q9NZC7; Q96G27: WBP1; NbExp=3; IntAct=EBI-4320739, EBI-3867685;
CC Q9NZC7; Q67FY2: Bcl9l; Xeno; NbExp=3; IntAct=EBI-4320739, EBI-5234367;
CC Q9NZC7; Q60838: Dvl2; Xeno; NbExp=2; IntAct=EBI-4320739, EBI-641940;
CC Q9NZC7; Q61527: Erbb4; Xeno; NbExp=3; IntAct=EBI-4320739, EBI-4398741;
CC Q9NZC7-5; Q8NFV4-4: ABHD11; NbExp=3; IntAct=EBI-12040603, EBI-12318443;
CC Q9NZC7-5; Q9NYB9-2: ABI2; NbExp=5; IntAct=EBI-12040603, EBI-11096309;
CC Q9NZC7-5; Q9BWD1: ACAT2; NbExp=3; IntAct=EBI-12040603, EBI-1047273;
CC Q9NZC7-5; Q03154: ACY1; NbExp=3; IntAct=EBI-12040603, EBI-742064;
CC Q9NZC7-5; P18825: ADRA2C; NbExp=3; IntAct=EBI-12040603, EBI-12015266;
CC Q9NZC7-5; Q9NYG5-2: ANAPC11; NbExp=3; IntAct=EBI-12040603, EBI-12224467;
CC Q9NZC7-5; P50995: ANXA11; NbExp=3; IntAct=EBI-12040603, EBI-715243;
CC Q9NZC7-5; Q96B67: ARRDC3; NbExp=8; IntAct=EBI-12040603, EBI-2875665;
CC Q9NZC7-5; Q86V38: ATN1; NbExp=3; IntAct=EBI-12040603, EBI-11954292;
CC Q9NZC7-5; Q5SWW7: C10orf55; NbExp=3; IntAct=EBI-12040603, EBI-12809220;
CC Q9NZC7-5; Q6NUJ2: C11orf87; NbExp=3; IntAct=EBI-12040603, EBI-6660291;
CC Q9NZC7-5; Q5BKX5-3: C19orf54; NbExp=3; IntAct=EBI-12040603, EBI-11976299;
CC Q9NZC7-5; Q8N4L8: CCDC24; NbExp=3; IntAct=EBI-12040603, EBI-1104933;
CC Q9NZC7-5; P40199: CEACAM6; NbExp=3; IntAct=EBI-12040603, EBI-4314501;
CC Q9NZC7-5; Q8NE01: CNNM3; NbExp=3; IntAct=EBI-12040603, EBI-741032;
CC Q9NZC7-5; Q16630-2: CPSF6; NbExp=3; IntAct=EBI-12040603, EBI-11088043;
CC Q9NZC7-5; Q02930-3: CREB5; NbExp=3; IntAct=EBI-12040603, EBI-10192698;
CC Q9NZC7-5; P02489: CRYAA; NbExp=3; IntAct=EBI-12040603, EBI-6875961;
CC Q9NZC7-5; P67870: CSNK2B; NbExp=3; IntAct=EBI-12040603, EBI-348169;
CC Q9NZC7-5; P78358: CTAG1B; NbExp=3; IntAct=EBI-12040603, EBI-1188472;
CC Q9NZC7-5; Q9GZU7: CTDSP1; NbExp=3; IntAct=EBI-12040603, EBI-751587;
CC Q9NZC7-5; Q15038: DAZAP2; NbExp=6; IntAct=EBI-12040603, EBI-724310;
CC Q9NZC7-5; Q9NQL9: DMRT3; NbExp=3; IntAct=EBI-12040603, EBI-9679045;
CC Q9NZC7-5; G5E9A7: DMWD; NbExp=3; IntAct=EBI-12040603, EBI-10976677;
CC Q9NZC7-5; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-12040603, EBI-744099;
CC Q9NZC7-5; P00488: F13A1; NbExp=3; IntAct=EBI-12040603, EBI-2565863;
CC Q9NZC7-5; Q7L5A3: FAM214B; NbExp=3; IntAct=EBI-12040603, EBI-745689;
CC Q9NZC7-5; Q8WU58: FAM222B; NbExp=5; IntAct=EBI-12040603, EBI-2807642;
CC Q9NZC7-5; Q9BSK4: FEM1A; NbExp=3; IntAct=EBI-12040603, EBI-2515349;
CC Q9NZC7-5; Q9NU39: FOXD4L1; NbExp=3; IntAct=EBI-12040603, EBI-11320806;
CC Q9NZC7-5; Q12951-2: FOXI1; NbExp=3; IntAct=EBI-12040603, EBI-12018822;
CC Q9NZC7-5; O43559: FRS3; NbExp=3; IntAct=EBI-12040603, EBI-725515;
CC Q9NZC7-5; O75603: GCM2; NbExp=3; IntAct=EBI-12040603, EBI-10188645;
CC Q9NZC7-5; P55040: GEM; NbExp=3; IntAct=EBI-12040603, EBI-744104;
CC Q9NZC7-5; P14136: GFAP; NbExp=3; IntAct=EBI-12040603, EBI-744302;
CC Q9NZC7-5; Q9BZE0: GLIS2; NbExp=3; IntAct=EBI-12040603, EBI-7251368;
CC Q9NZC7-5; Q9Y223-2: GNE; NbExp=3; IntAct=EBI-12040603, EBI-11975289;
CC Q9NZC7-5; P28799: GRN; NbExp=3; IntAct=EBI-12040603, EBI-747754;
CC Q9NZC7-5; P49639: HOXA1; NbExp=3; IntAct=EBI-12040603, EBI-740785;
CC Q9NZC7-5; P31273: HOXC8; NbExp=3; IntAct=EBI-12040603, EBI-1752118;
CC Q9NZC7-5; P04792: HSPB1; NbExp=3; IntAct=EBI-12040603, EBI-352682;
CC Q9NZC7-5; Q16082: HSPB2; NbExp=3; IntAct=EBI-12040603, EBI-739395;
CC Q9NZC7-5; Q8IZ03: IFIT2; NbExp=3; IntAct=EBI-12040603, EBI-746217;
CC Q9NZC7-5; Q0VD86: INCA1; NbExp=3; IntAct=EBI-12040603, EBI-6509505;
CC Q9NZC7-5; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-12040603, EBI-1055254;
CC Q9NZC7-5; Q92993: KAT5; NbExp=3; IntAct=EBI-12040603, EBI-399080;
CC Q9NZC7-5; O60333-2: KIF1B; NbExp=3; IntAct=EBI-12040603, EBI-10975473;
CC Q9NZC7-5; Q96G42: KLHDC7B; NbExp=3; IntAct=EBI-12040603, EBI-9478422;
CC Q9NZC7-5; Q2WGJ6: KLHL38; NbExp=3; IntAct=EBI-12040603, EBI-6426443;
CC Q9NZC7-5; Q92876: KLK6; NbExp=3; IntAct=EBI-12040603, EBI-2432309;
CC Q9NZC7-5; P12035: KRT3; NbExp=3; IntAct=EBI-12040603, EBI-2430095;
CC Q9NZC7-5; O76011: KRT34; NbExp=3; IntAct=EBI-12040603, EBI-1047093;
CC Q9NZC7-5; O95678: KRT75; NbExp=3; IntAct=EBI-12040603, EBI-2949715;
CC Q9NZC7-5; Q8IUC1: KRTAP11-1; NbExp=3; IntAct=EBI-12040603, EBI-1052037;
CC Q9NZC7-5; Q14847-2: LASP1; NbExp=3; IntAct=EBI-12040603, EBI-9088686;
CC Q9NZC7-5; Q99732: LITAF; NbExp=3; IntAct=EBI-12040603, EBI-725647;
CC Q9NZC7-5; Q8TAP4-4: LMO3; NbExp=6; IntAct=EBI-12040603, EBI-11742507;
CC Q9NZC7-5; Q71SY5: MED25; NbExp=3; IntAct=EBI-12040603, EBI-394558;
CC Q9NZC7-5; Q13064: MKRN3; NbExp=3; IntAct=EBI-12040603, EBI-2340269;
CC Q9NZC7-5; Q9HB07: MYG1; NbExp=3; IntAct=EBI-12040603, EBI-709754;
CC Q9NZC7-5; Q9NP98: MYOZ1; NbExp=3; IntAct=EBI-12040603, EBI-744402;
CC Q9NZC7-5; Q9NPC6: MYOZ2; NbExp=3; IntAct=EBI-12040603, EBI-746712;
CC Q9NZC7-5; P19404: NDUFV2; NbExp=3; IntAct=EBI-12040603, EBI-713665;
CC Q9NZC7-5; Q14511-2: NEDD9; NbExp=3; IntAct=EBI-12040603, EBI-11746523;
CC Q9NZC7-5; P29474: NOS3; NbExp=3; IntAct=EBI-12040603, EBI-1391623;
CC Q9NZC7-5; Q7RTU3: OLIG3; NbExp=3; IntAct=EBI-12040603, EBI-10225049;
CC Q9NZC7-5; P32242: OTX1; NbExp=3; IntAct=EBI-12040603, EBI-740446;
CC Q9NZC7-5; Q86TB9: PATL1; NbExp=5; IntAct=EBI-12040603, EBI-2562092;
CC Q9NZC7-5; Q9HBE1-4: PATZ1; NbExp=5; IntAct=EBI-12040603, EBI-11022007;
CC Q9NZC7-5; P55771: PAX9; NbExp=3; IntAct=EBI-12040603, EBI-12111000;
CC Q9NZC7-5; Q9BYU1: PBX4; NbExp=3; IntAct=EBI-12040603, EBI-10302990;
CC Q9NZC7-5; Q9UBV8: PEF1; NbExp=3; IntAct=EBI-12040603, EBI-724639;
CC Q9NZC7-5; Q99697-2: PITX2; NbExp=3; IntAct=EBI-12040603, EBI-12138495;
CC Q9NZC7-5; Q494U1-3: PLEKHN1; NbExp=3; IntAct=EBI-12040603, EBI-12014286;
CC Q9NZC7-5; Q9NRY6: PLSCR3; NbExp=3; IntAct=EBI-12040603, EBI-750734;
CC Q9NZC7-5; P62937-2: PPIA; NbExp=3; IntAct=EBI-12040603, EBI-25884072;
CC Q9NZC7-5; P23284: PPIB; NbExp=3; IntAct=EBI-12040603, EBI-359252;
CC Q9NZC7-5; Q7Z5V6-2: PPP1R32; NbExp=3; IntAct=EBI-12040603, EBI-12000762;
CC Q9NZC7-5; P17252: PRKCA; NbExp=3; IntAct=EBI-12040603, EBI-1383528;
CC Q9NZC7-5; P60891: PRPS1; NbExp=3; IntAct=EBI-12040603, EBI-749195;
CC Q9NZC7-5; P28062-2: PSMB8; NbExp=3; IntAct=EBI-12040603, EBI-372312;
CC Q9NZC7-5; Q9BTL3: RAMAC; NbExp=3; IntAct=EBI-12040603, EBI-744023;
CC Q9NZC7-5; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-12040603, EBI-396669;
CC Q9NZC7-5; Q9BVN2: RUSC1; NbExp=3; IntAct=EBI-12040603, EBI-6257312;
CC Q9NZC7-5; Q8IYX7: SAXO1; NbExp=3; IntAct=EBI-12040603, EBI-3957636;
CC Q9NZC7-5; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-12040603, EBI-9090795;
CC Q9NZC7-5; Q9H788: SH2D4A; NbExp=5; IntAct=EBI-12040603, EBI-747035;
CC Q9NZC7-5; Q92529: SHC3; NbExp=5; IntAct=EBI-12040603, EBI-79084;
CC Q9NZC7-5; Q16348: SLC15A2; NbExp=3; IntAct=EBI-12040603, EBI-12806032;
CC Q9NZC7-5; Q99954: SMR3A; NbExp=3; IntAct=EBI-12040603, EBI-12067698;
CC Q9NZC7-5; P09234: SNRPC; NbExp=3; IntAct=EBI-12040603, EBI-766589;
CC Q9NZC7-5; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-12040603, EBI-5235340;
CC Q9NZC7-5; Q9BT92: TCHP; NbExp=3; IntAct=EBI-12040603, EBI-740781;
CC Q9NZC7-5; Q9BXF9: TEKT3; NbExp=3; IntAct=EBI-12040603, EBI-8644516;
CC Q9NZC7-5; Q96LM6: TEX37; NbExp=3; IntAct=EBI-12040603, EBI-743976;
CC Q9NZC7-5; Q92734: TFG; NbExp=3; IntAct=EBI-12040603, EBI-357061;
CC Q9NZC7-5; Q86WT6-2: TRIM69; NbExp=3; IntAct=EBI-12040603, EBI-11525489;
CC Q9NZC7-5; Q3SY00: TSGA10IP; NbExp=5; IntAct=EBI-12040603, EBI-10241197;
CC Q9NZC7-5; Q6NVU6: UFSP1; NbExp=3; IntAct=EBI-12040603, EBI-12068150;
CC Q9NZC7-5; O95231: VENTX; NbExp=5; IntAct=EBI-12040603, EBI-10191303;
CC Q9NZC7-5; Q14119: VEZF1; NbExp=3; IntAct=EBI-12040603, EBI-11980193;
CC Q9NZC7-5; A5D8V6: VPS37C; NbExp=3; IntAct=EBI-12040603, EBI-2559305;
CC Q9NZC7-5; O76024: WFS1; NbExp=3; IntAct=EBI-12040603, EBI-720609;
CC Q9NZC7-5; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-12040603, EBI-12040603;
CC Q9NZC7-5; P61981: YWHAG; NbExp=3; IntAct=EBI-12040603, EBI-359832;
CC Q9NZC7-5; A0A0C4DGF1: ZBTB32; NbExp=6; IntAct=EBI-12040603, EBI-10188476;
CC Q9NZC7-5; Q15915: ZIC1; NbExp=3; IntAct=EBI-12040603, EBI-11963196;
CC Q9NZC7-5; P52742: ZNF135; NbExp=3; IntAct=EBI-12040603, EBI-7101455;
CC Q9NZC7-5; Q96IQ9: ZNF414; NbExp=3; IntAct=EBI-12040603, EBI-744257;
CC Q9NZC7-5; Q9P0T4: ZNF581; NbExp=3; IntAct=EBI-12040603, EBI-745520;
CC Q9NZC7-5; Q96EJ4; NbExp=3; IntAct=EBI-12040603, EBI-750454;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14695174,
CC ECO:0000269|PubMed:15070730, ECO:0000269|PubMed:16219768,
CC ECO:0000269|PubMed:19366691, ECO:0000269|PubMed:19465938}. Nucleus
CC {ECO:0000269|PubMed:14695174, ECO:0000269|PubMed:15064722,
CC ECO:0000269|PubMed:16219768, ECO:0000269|PubMed:19366691}.
CC Mitochondrion {ECO:0000269|PubMed:14695174}. Golgi apparatus
CC {ECO:0000305}. Note=Partially localizes to the mitochondria
CC (PubMed:14695174). Translocates to the nucleus upon genotoxic stress or
CC TNF stimulation (By similarity). Translocates to the nucleus in
CC response to TGFB1 (PubMed:19366691). Isoform 5 and isoform 6 may
CC localize in the nucleus. {ECO:0000250, ECO:0000269|PubMed:14695174,
CC ECO:0000269|PubMed:19366691}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1; Synonyms=FOR II, FOR2, WWOXv1, WWOX v8;
CC IsoId=Q9NZC7-1; Sequence=Displayed;
CC Name=2; Synonyms=FOR I, FOR1, WOX2, WWOXv2;
CC IsoId=Q9NZC7-2; Sequence=VSP_016367, VSP_016369;
CC Name=3; Synonyms=FOR III, FOR3, WOX3;
CC IsoId=Q9NZC7-3; Sequence=VSP_016364, VSP_016365;
CC Name=4; Synonyms=FOR IV;
CC IsoId=Q9NZC7-4; Sequence=VSP_016358, VSP_016359;
CC Name=5; Synonyms=WWOXdelta6-8, WWOXv4;
CC IsoId=Q9NZC7-5; Sequence=VSP_016363;
CC Name=6; Synonyms=WWOXdelta5-8, WWOXv3;
CC IsoId=Q9NZC7-6; Sequence=VSP_016360;
CC Name=7;
CC IsoId=Q9NZC7-7; Sequence=VSP_016362, VSP_016366;
CC -!- TISSUE SPECIFICITY: Widely expressed. Strongly expressed in testis,
CC prostate, and ovary. Overexpressed in cancer cell lines. Isoform 5 and
CC isoform 6 may only be expressed in tumor cell lines.
CC {ECO:0000269|PubMed:10786676, ECO:0000269|PubMed:11719429}.
CC -!- DOMAIN: The WW 1 domain mediates interaction with TP53, and probably
CC TP73, TFAP2C, LITAF and WBP1. {ECO:0000269|PubMed:15064722,
CC ECO:0000269|PubMed:15070730, ECO:0000269|PubMed:15548692}.
CC -!- PTM: Phosphorylated upon genotoxic stress. Phosphorylation of Tyr-33
CC regulates interaction with TP53, TP73 and MAPK8. May also regulate
CC proapoptotic activity. Phosphorylation by TNK2 is associated with
CC polyubiquitination and degradation. {ECO:0000269|PubMed:15070730,
CC ECO:0000269|PubMed:16288044, ECO:0000269|PubMed:19366691}.
CC -!- PTM: Ubiquitinated when phosphorylated by TNK2, leading to its
CC degradation. {ECO:0000269|PubMed:16288044}.
CC -!- DISEASE: Note=Defects in WWOX may be involved in several cancer types.
CC The gene spans the second most common chromosomal fragile site (FRA16D)
CC which is frequently altered in cancers (PubMed:10861292). Alteration of
CC the expression and expression of some isoforms is associated with
CC cancers. However, it is still unclear if alteration of WWOX is directly
CC implicated in cancerogenesis or if it corresponds to a secondary effect
CC (PubMed:10861292, PubMed:11572989, PubMed:15266310, PubMed:15073125,
CC PubMed:15131042). {ECO:0000269|PubMed:10861292,
CC ECO:0000269|PubMed:11572989, ECO:0000269|PubMed:15073125,
CC ECO:0000269|PubMed:15131042, ECO:0000269|PubMed:15266310}.
CC -!- DISEASE: Esophageal cancer (ESCR) [MIM:133239]: A malignancy of the
CC esophagus. The most common types are esophageal squamous cell carcinoma
CC and adenocarcinoma. Cancer of the esophagus remains a devastating
CC disease because it is usually not detected until it has progressed to
CC an advanced incurable stage. {ECO:0000269|PubMed:11956080}. Note=The
CC disease may be caused by variants affecting the gene represented in
CC this entry.
CC -!- DISEASE: Spinocerebellar ataxia, autosomal recessive, 12 (SCAR12)
CC [MIM:614322]: A form of spinocerebellar ataxia, a clinically and
CC genetically heterogeneous group of cerebellar disorders. Patients show
CC progressive incoordination of gait and often poor coordination of
CC hands, speech and eye movements, due to degeneration of the cerebellum
CC with variable involvement of the brainstem and spinal cord. SCAR12 is
CC additionally characterized by onset of generalized seizures in infancy,
CC and delayed psychomotor development with intellectual disability. Some
CC patients may also show spasticity. {ECO:0000269|PubMed:24369382,
CC ECO:0000269|PubMed:24456803}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Developmental and epileptic encephalopathy 28 (DEE28)
CC [MIM:616211]: A form of epileptic encephalopathy, a heterogeneous group
CC of severe early-onset epilepsies characterized by refractory seizures,
CC neurodevelopmental impairment, and poor prognosis. Development is
CC normal prior to seizure onset, after which cognitive and motor delays
CC become apparent. {ECO:0000269|PubMed:25411445}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP94227.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/WWOXID508ch16q23.html";
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DR EMBL; AF211943; AAF27049.1; -; mRNA.
DR EMBL; AF212843; AAF27050.1; -; Genomic_DNA.
DR EMBL; AH009490; AAF78197.1; -; Genomic_DNA.
DR EMBL; AF227526; AAF82053.1; -; mRNA.
DR EMBL; AF227527; AAF82054.1; -; mRNA.
DR EMBL; AF227528; AAF82055.1; -; mRNA.
DR EMBL; AF227529; AAF82056.1; -; mRNA.
DR EMBL; AF395123; AAK81727.1; -; mRNA.
DR EMBL; AF395124; AAK81728.1; -; mRNA.
DR EMBL; AF325432; AAL05449.1; -; Genomic_DNA.
DR EMBL; AF325423; AAL05449.1; JOINED; Genomic_DNA.
DR EMBL; AF325424; AAL05449.1; JOINED; Genomic_DNA.
DR EMBL; AF325425; AAL05449.1; JOINED; Genomic_DNA.
DR EMBL; AF325426; AAL05449.1; JOINED; Genomic_DNA.
DR EMBL; AF325427; AAL05449.1; JOINED; Genomic_DNA.
DR EMBL; AF325428; AAL05449.1; JOINED; Genomic_DNA.
DR EMBL; AF325430; AAL05449.1; JOINED; Genomic_DNA.
DR EMBL; AF325431; AAL05449.1; JOINED; Genomic_DNA.
DR EMBL; AF325429; AAL05450.1; -; Genomic_DNA.
DR EMBL; AF325423; AAL05450.1; JOINED; Genomic_DNA.
DR EMBL; AF325424; AAL05450.1; JOINED; Genomic_DNA.
DR EMBL; AF325425; AAL05450.1; JOINED; Genomic_DNA.
DR EMBL; AF325426; AAL05450.1; JOINED; Genomic_DNA.
DR EMBL; AF325427; AAL05450.1; JOINED; Genomic_DNA.
DR EMBL; AF325432; AAL05451.1; -; Genomic_DNA.
DR EMBL; AF325423; AAL05451.1; JOINED; Genomic_DNA.
DR EMBL; AF325424; AAL05451.1; JOINED; Genomic_DNA.
DR EMBL; AF325425; AAL05451.1; JOINED; Genomic_DNA.
DR EMBL; AF325426; AAL05451.1; JOINED; Genomic_DNA.
DR EMBL; AF325433; AAL05451.1; JOINED; Genomic_DNA.
DR EMBL; AY256821; AAP94227.1; ALT_FRAME; mRNA.
DR EMBL; AK290438; BAF83127.1; -; mRNA.
DR EMBL; BT007445; AAP36113.1; -; mRNA.
DR EMBL; BC003184; AAH03184.1; -; mRNA.
DR CCDS; CCDS42196.1; -. [Q9NZC7-1]
DR CCDS; CCDS42197.1; -. [Q9NZC7-3]
DR RefSeq; NP_001278926.1; NM_001291997.1.
DR RefSeq; NP_057457.1; NM_016373.3. [Q9NZC7-1]
DR RefSeq; NP_570607.1; NM_130791.3. [Q9NZC7-3]
DR PDB; 1WMV; NMR; -; A=51-101.
DR PDBsum; 1WMV; -.
DR AlphaFoldDB; Q9NZC7; -.
DR SMR; Q9NZC7; -.
DR BioGRID; 119707; 616.
DR IntAct; Q9NZC7; 148.
DR MINT; Q9NZC7; -.
DR STRING; 9606.ENSP00000457230; -.
DR iPTMnet; Q9NZC7; -.
DR PhosphoSitePlus; Q9NZC7; -.
DR BioMuta; WWOX; -.
DR DMDM; 74725363; -.
DR EPD; Q9NZC7; -.
DR jPOST; Q9NZC7; -.
DR MassIVE; Q9NZC7; -.
DR MaxQB; Q9NZC7; -.
DR PaxDb; Q9NZC7; -.
DR PeptideAtlas; Q9NZC7; -.
DR PRIDE; Q9NZC7; -.
DR ProteomicsDB; 83364; -. [Q9NZC7-1]
DR ProteomicsDB; 83365; -. [Q9NZC7-2]
DR ProteomicsDB; 83366; -. [Q9NZC7-3]
DR ProteomicsDB; 83367; -. [Q9NZC7-4]
DR ProteomicsDB; 83368; -. [Q9NZC7-5]
DR ProteomicsDB; 83369; -. [Q9NZC7-6]
DR ProteomicsDB; 83370; -. [Q9NZC7-7]
DR Antibodypedia; 8291; 384 antibodies from 41 providers.
DR DNASU; 51741; -.
DR Ensembl; ENST00000355860.7; ENSP00000348119.3; ENSG00000186153.18. [Q9NZC7-3]
DR Ensembl; ENST00000402655.6; ENSP00000384238.2; ENSG00000186153.18. [Q9NZC7-6]
DR Ensembl; ENST00000406884.6; ENSP00000384495.2; ENSG00000186153.18. [Q9NZC7-5]
DR Ensembl; ENST00000408984.7; ENSP00000386161.3; ENSG00000186153.18. [Q9NZC7-2]
DR Ensembl; ENST00000566780.6; ENSP00000457230.1; ENSG00000186153.18. [Q9NZC7-1]
DR Ensembl; ENST00000569818.1; ENSP00000454485.1; ENSG00000186153.18. [Q9NZC7-4]
DR GeneID; 51741; -.
DR KEGG; hsa:51741; -.
DR MANE-Select; ENST00000566780.6; ENSP00000457230.1; NM_016373.4; NP_057457.1.
DR UCSC; uc002ffi.3; human. [Q9NZC7-1]
DR CTD; 51741; -.
DR DisGeNET; 51741; -.
DR GeneCards; WWOX; -.
DR HGNC; HGNC:12799; WWOX.
DR HPA; ENSG00000186153; Low tissue specificity.
DR MalaCards; WWOX; -.
DR MIM; 133239; phenotype.
DR MIM; 605131; gene.
DR MIM; 614322; phenotype.
DR MIM; 616211; phenotype.
DR neXtProt; NX_Q9NZC7; -.
DR NIAGADS; ENSG00000186153; -.
DR OpenTargets; ENSG00000186153; -.
DR Orphanet; 251510; 46,XY partial gonadal dysgenesis.
DR Orphanet; 284282; Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to WWOX deficiency.
DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy.
DR Orphanet; 99977; Squamous cell carcinoma of the esophagus.
DR PharmGKB; PA37398; -.
DR VEuPathDB; HostDB:ENSG00000186153; -.
DR eggNOG; KOG1208; Eukaryota.
DR GeneTree; ENSGT00940000157389; -.
DR HOGENOM; CLU_010194_44_0_1; -.
DR InParanoid; Q9NZC7; -.
DR OMA; VHPGNMV; -.
DR OrthoDB; 1413827at2759; -.
DR PhylomeDB; Q9NZC7; -.
DR TreeFam; TF105428; -.
DR PathwayCommons; Q9NZC7; -.
DR Reactome; R-HSA-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-HSA-8866904; Negative regulation of activity of TFAP2 (AP-2) family transcription factors.
DR Reactome; R-HSA-8866907; Activation of the TFAP2 (AP-2) family of transcription factors.
DR SignaLink; Q9NZC7; -.
DR SIGNOR; Q9NZC7; -.
DR BioGRID-ORCS; 51741; 8 hits in 1080 CRISPR screens.
DR ChiTaRS; WWOX; human.
DR EvolutionaryTrace; Q9NZC7; -.
DR GeneWiki; WWOX; -.
DR GenomeRNAi; 51741; -.
DR Pharos; Q9NZC7; Tbio.
DR PRO; PR:Q9NZC7; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9NZC7; protein.
DR Bgee; ENSG00000186153; Expressed in parotid gland and 199 other tissues.
DR ExpressionAtlas; Q9NZC7; baseline and differential.
DR Genevisible; Q9NZC7; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:BHF-UCL.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISS:BHF-UCL.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0016491; F:oxidoreductase activity; NAS:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IEA:Ensembl.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:BHF-UCL.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; IEA:Ensembl.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; ISS:BHF-UCL.
DR GO; GO:2001241; P:positive regulation of extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
DR GO; GO:0048705; P:skeletal system morphogenesis; ISS:BHF-UCL.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR CDD; cd09809; human_WWOX_like_SDR_c-like; 1.
DR CDD; cd00201; WW; 2.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR InterPro; IPR001202; WW_dom.
DR InterPro; IPR036020; WW_dom_sf.
DR InterPro; IPR042732; WWOX_SDR_c-like.
DR Pfam; PF00106; adh_short; 1.
DR Pfam; PF00397; WW; 2.
DR PRINTS; PR00081; GDHRDH.
DR SMART; SM00456; WW; 2.
DR SUPFAM; SSF51045; SSF51045; 2.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS01159; WW_DOMAIN_1; 2.
DR PROSITE; PS50020; WW_DOMAIN_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Cytoplasm; Disease variant;
KW Epilepsy; Golgi apparatus; Mitochondrion; NADP; Neurodegeneration; Nucleus;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Repeat;
KW Tumor suppressor; Ubl conjugation; Wnt signaling pathway.
FT CHAIN 1..414
FT /note="WW domain-containing oxidoreductase"
FT /id="PRO_0000054815"
FT DOMAIN 16..49
FT /note="WW 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 57..90
FT /note="WW 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 125..414
FT /note="Interaction with MAPT"
FT /evidence="ECO:0000250"
FT REGION 209..273
FT /note="Mediates targeting to the mitochondria"
FT /evidence="ECO:0000250"
FT MOTIF 50..55
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT ACT_SITE 293
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 131..137
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 260
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 12
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 33
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:15070730,
FT ECO:0000269|PubMed:19366691"
FT MOD_RES 287
FT /note="Phosphotyrosine; by TNK2"
FT /evidence="ECO:0000269|PubMed:16288044"
FT VAR_SEQ 36
FT /note="N -> K (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:10861292"
FT /id="VSP_016358"
FT VAR_SEQ 37..414
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:10861292"
FT /id="VSP_016359"
FT VAR_SEQ 137..414
FT /note="GFETAKSFALHGAHVILACRNMARASEAVSRILEEWHKAKVEAMTLDLALLR
FT SVQHFAEAFKAKNVPLHVLVCNAATFALPWSLTKDGLETTFQVNHLGHFYLVQLLQDVL
FT CRSAPARVIVVSSESHRFTDINDSLGKLDFSRLSPTKNDYWAMLAYNRSKLCNILFSNE
FT LHRRLSPRGVTSNAVHPGNMMYSNIHRSWWVYTLLFTLARPFTKSMQQGAATTVYCAAV
FT PELEGLGGMYFNNCCRCMPSPEAQSEETARTLWALSERLIQERLGSQSG -> ATGSCH
FT HRVLCCCPRTGGSGRDVLQQLLPLHALTRSSERRDGPDPVGAQREADPRTAWQPVRLSG
FT AQSGWAHTPALCVSPHASARAGPLPNVPPTQIRKSKGNKSSHNRVKNLKYQWEAGNSWG
FT KVSLFWGWARHRSLCFLVVACLKVKTCLVCRFRISLEKHQQFSFFYCYRIA (in
FT isoform 6)"
FT /evidence="ECO:0000303|PubMed:11719429"
FT /id="VSP_016360"
FT VAR_SEQ 138..213
FT /note="FETAKSFALHGAHVILACRNMARASEAVSRILEEWHKAKVEAMTLDLALLRS
FT VQHFAEAFKAKNVPLHVLVCNAAT -> KASCHVGRTLKHTRVEELSLLPTAINRELPP
FT PCTVLLSQNWRVWEGCTSTTAAAACPHQKLRAKRRPGPCGRSARG (in isoform
FT 7)"
FT /evidence="ECO:0000305"
FT /id="VSP_016362"
FT VAR_SEQ 173..352
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:11719429,
FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.7"
FT /id="VSP_016363"
FT VAR_SEQ 173..189
FT /note="HKAKVEAMTLDLALLRS -> KTKYHPPPEKCRIKIFH (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:10861292"
FT /id="VSP_016364"
FT VAR_SEQ 190..414
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10861292"
FT /id="VSP_016365"
FT VAR_SEQ 214..414
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000305"
FT /id="VSP_016366"
FT VAR_SEQ 353..363
FT /note="QQGAATTVYCA -> VSDCLVEGGHF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10861292"
FT /id="VSP_016367"
FT VAR_SEQ 364..414
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10861292"
FT /id="VSP_016369"
FT VARIANT 47
FT /note="P -> R (in DEE28; dbSNP:rs730880292)"
FT /evidence="ECO:0000269|PubMed:25411445"
FT /id="VAR_072351"
FT VARIANT 47
FT /note="P -> T (in SCAR12; dbSNP:rs587777128)"
FT /evidence="ECO:0000269|PubMed:24369382"
FT /id="VAR_070992"
FT VARIANT 98
FT /note="P -> L (in dbSNP:rs144601717)"
FT /evidence="ECO:0000269|PubMed:11572989"
FT /id="VAR_023916"
FT VARIANT 111
FT /note="T -> S (in a Burkitt lymphoma cell line;
FT dbSNP:rs114755364)"
FT /evidence="ECO:0000269|PubMed:11572989"
FT /id="VAR_023917"
FT VARIANT 120
FT /note="R -> W (in a primary colorectal tumor and a
FT histiocytic lymphoma cell line; dbSNP:rs141361080)"
FT /evidence="ECO:0000269|PubMed:11572989"
FT /id="VAR_023918"
FT VARIANT 179
FT /note="A -> T (in dbSNP:rs11545029)"
FT /evidence="ECO:0000269|PubMed:11572989, ECO:0000269|Ref.5"
FT /id="VAR_023919"
FT VARIANT 216
FT /note="L -> V (in dbSNP:rs7201683)"
FT /id="VAR_052323"
FT VARIANT 272
FT /note="L -> F (in dbSNP:rs186745328)"
FT /evidence="ECO:0000269|PubMed:11572989"
FT /id="VAR_023920"
FT VARIANT 282
FT /note="P -> A (in dbSNP:rs3764340)"
FT /evidence="ECO:0000269|PubMed:11572989"
FT /id="VAR_023921"
FT VARIANT 291
FT /note="L -> P (found in a esophageal cancer sample; somatic
FT mutation; dbSNP:rs119487098)"
FT /evidence="ECO:0000269|PubMed:11956080"
FT /id="VAR_023922"
FT VARIANT 314
FT /note="R -> H (in dbSNP:rs73572838)"
FT /evidence="ECO:0000269|PubMed:11572989"
FT /id="VAR_023923"
FT VARIANT 372
FT /note="G -> R (in SCAR12; dbSNP:rs587777127)"
FT /evidence="ECO:0000269|PubMed:24369382"
FT /id="VAR_070993"
FT MUTAGEN 28
FT /note="K->T: No effect on interaction with TP53. Abolishes
FT interaction with MAPK8; when associated with V-29."
FT /evidence="ECO:0000269|PubMed:12514174"
FT MUTAGEN 29
FT /note="D->V: No effect on interaction with TP53. Abolishes
FT interaction with MAPK8; when associated with T-28."
FT /evidence="ECO:0000269|PubMed:12514174"
FT MUTAGEN 33
FT /note="Y->F: Loss of phosphorylation."
FT /evidence="ECO:0000269|PubMed:12514174,
FT ECO:0000269|PubMed:15070730"
FT MUTAGEN 33
FT /note="Y->R: Abolishes interaction with TP53, TP73, MAPK8
FT and ERBB4. Partial loss of interaction with TFAP2C. Loss of
FT phosphorylation. Loss of the proapoptotic activity."
FT /evidence="ECO:0000269|PubMed:12514174,
FT ECO:0000269|PubMed:15070730"
FT MUTAGEN 44..47
FT /note="WEHP->FEHA: Abolishes interaction with LITAF."
FT /evidence="ECO:0000269|PubMed:15064722"
FT MUTAGEN 61
FT /note="Y->R: No effect on interaction with TP73."
FT /evidence="ECO:0000269|PubMed:15070730"
FT MUTAGEN 85..88
FT /note="YLDP->ALDA: No effect on interaction with LITAF."
FT /evidence="ECO:0000269|PubMed:15064722"
FT MUTAGEN 287
FT /note="Y->A: Loss of phosphorylation by TNK2."
FT /evidence="ECO:0000269|PubMed:16288044"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:1WMV"
FT STRAND 73..80
FT /evidence="ECO:0007829|PDB:1WMV"
FT STRAND 83..86
FT /evidence="ECO:0007829|PDB:1WMV"
FT VARIANT Q9NZC7-3:182
FT /note="K -> E (found in a primary colorectal tumor and
FT tumor cells; dbSNP:rs77067228)"
FT /evidence="ECO:0000305"
FT /id="VAR_082915"
SQ SEQUENCE 414 AA; 46677 MW; E4D9A649E6CB05DF CRC64;
MAALRYAGLD DTDSEDELPP GWEERTTKDG WVYYANHTEE KTQWEHPKTG KRKRVAGDLP
YGWEQETDEN GQVFFVDHIN KRTTYLDPRL AFTVDDNPTK PTTRQRYDGS TTAMEILQGR
DFTGKVVVVT GANSGIGFET AKSFALHGAH VILACRNMAR ASEAVSRILE EWHKAKVEAM
TLDLALLRSV QHFAEAFKAK NVPLHVLVCN AATFALPWSL TKDGLETTFQ VNHLGHFYLV
QLLQDVLCRS APARVIVVSS ESHRFTDIND SLGKLDFSRL SPTKNDYWAM LAYNRSKLCN
ILFSNELHRR LSPRGVTSNA VHPGNMMYSN IHRSWWVYTL LFTLARPFTK SMQQGAATTV
YCAAVPELEG LGGMYFNNCC RCMPSPEAQS EETARTLWAL SERLIQERLG SQSG
