ID ZEB1_HUMAN Reviewed; 1124 AA. AC P37275; B4DJV0; B4DUW9; E9PCM7; F5H4I8; Q12924; Q13800; Q2KJ05; Q5T968; AC Q5VZ84; Q8NB68; DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1999, sequence version 2. DT 07-APR-2021, entry version 210. DE RecName: Full=Zinc finger E-box-binding homeobox 1; DE AltName: Full=NIL-2-A zinc finger protein; DE AltName: Full=Negative regulator of IL2; DE AltName: Full=Transcription factor 8; DE Short=TCF-8; GN Name=ZEB1; Synonyms=AREB6, TCF8; 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). RX PubMed=8138542; DOI=10.1093/oxfordjournals.jbchem.a124267; RA Watanabe Y., Kawakami K., Hirayama Y., Nagano K.; RT "Transcription factors positively and negatively regulating the Na,K-ATPase RT alpha 1 subunit gene."; RL J. Biochem. 114:849-855(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Bachman N.J., Scarpulla R.C.; RT "A human zinc finger homeodomain protein homologous to the chicken delta- RT crystallin enhancer binding protein, delta EF1."; RL Submitted (JUL-1994) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 1-798 (ISOFORM 5). RC TISSUE=Brain, and Thalamus; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). 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 [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 390-1124. RX PubMed=1840704; DOI=10.1126/science.1840704; RA Williams T.M., Moolten D., Burlein J., Romano J., Bhaerman R., Godillot A., RA Mellon M., Rauscher F.J. III, Kant J.A.; RT "Identification of a zinc finger protein that inhibits IL-2 gene RT expression."; RL Science 254:1791-1794(1991). RN [8] RP INVOLVEMENT IN PPCD3. RX PubMed=16252232; DOI=10.1086/497348; RA Krafchak C.M., Pawar H., Moroi S.E., Sugar A., Lichter P.R., Mackey D.A., RA Mian S., Nairus T., Elner V., Schteingart M.T., Downs C.A., Kijek T.G., RA Johnson J.M., Trager E.H., Rozsa F.W., Mandal M.N.A., Epstein M.P., RA Vollrath D., Ayyagari R., Boehnke M., Richards J.E.; RT "Mutations in TCF8 cause posterior polymorphous corneal dystrophy and RT ectopic expression of COL4A3 by corneal endothelial cells."; RL Am. J. Hum. Genet. 77:694-708(2005). RN [9] RP SUMOYLATION AT LYS-347 AND LYS-774. RX PubMed=16061479; DOI=10.1074/jbc.m504477200; RA Long J., Zuo D., Park M.; RT "Pc2-mediated sumoylation of Smad-interacting protein 1 attenuates RT transcriptional repression of E-cadherin."; RL J. Biol. Chem. 280:35477-35489(2005). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-322, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [13] RP FUNCTION. RX PubMed=19935649; DOI=10.1038/ncb1998; RA Wellner U., Schubert J., Burk U.C., Schmalhofer O., Zhu F., Sonntag A., RA Waldvogel B., Vannier C., Darling D., zur Hausen A., Brunton V.G., RA Morton J., Sansom O., Schuler J., Stemmler M.P., Herzberger C., Hopt U., RA Keck T., Brabletz S., Brabletz T.; RT "The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness- RT inhibiting microRNAs."; RL Nat. Cell Biol. 11:1487-1495(2009). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-642; SER-679 AND THR-702, 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 [15] RP FUNCTION. RX PubMed=20175752; DOI=10.1042/bj20091578; RA Papadopoulou V., Postigo A., Sanchez-Tillo E., Porter A.C., Wagner S.D.; RT "ZEB1 and CtBP form a repressive complex at a distal promoter element of RT the BCL6 locus."; RL Biochem. J. 427:541-550(2010). RN [16] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SMARCA4, AND TISSUE RP SPECIFICITY. RX PubMed=20418909; DOI=10.1038/onc.2010.102; RA Sanchez-Tillo E., Lazaro A., Torrent R., Cuatrecasas M., Vaquero E.C., RA Castells A., Engel P., Postigo A.; RT "ZEB1 represses E-cadherin and induces an EMT by recruiting the SWI/SNF RT chromatin-remodeling protein BRG1."; RL Oncogene 29:3490-3500(2010). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-679, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-679 AND THR-702, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [20] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-493; LYS-504 AND LYS-515, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [21] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-493, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25114211; DOI=10.1073/pnas.1413825111; RA Impens F., Radoshevich L., Cossart P., Ribet D.; RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by RT external stimuli."; RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014). RN [22] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-493; LYS-504 AND LYS-515, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033; RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V., RA Vertegaal A.C.; RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage."; RL Cell Rep. 10:1778-1791(2015). RN [23] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-493; LYS-504 AND LYS-515, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25755297; DOI=10.1074/mcp.o114.044792; RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V., RA Vertegaal A.C.; RT "System-wide analysis of SUMOylation dynamics in response to replication RT stress reveals novel small ubiquitin-like modified target proteins and RT acceptor lysines relevant for genome stability."; RL Mol. Cell. Proteomics 14:1419-1434(2015). RN [24] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-186; LYS-195; LYS-307; LYS-331; RP LYS-335; LYS-347; LYS-439; LYS-493; LYS-504; LYS-515; LYS-548; LYS-553 AND RP LYS-774, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [25] RP STRUCTURE BY NMR OF 583-642. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the homeobox domain from human NIL-2-A zinc finger RT protein, transcription factor 8."; RL Submitted (APR-2007) to the PDB data bank. RN [26] RP VARIANTS FECD6 THR-78; ALA-649; PRO-810; PRO-840 AND THR-905. RX PubMed=20036349; DOI=10.1016/j.ajhg.2009.12.001; RA Riazuddin S.A., Zaghloul N.A., Al-Saif A., Davey L., Diplas B.H., RA Meadows D.N., Eghrari A.O., Minear M.A., Li Y.J., Klintworth G.K., RA Afshari N., Gregory S.G., Gottsch J.D., Katsanis N.; RT "Missense mutations in TCF8 cause late-onset Fuchs corneal dystrophy and RT interact with FCD4 on chromosome 9p."; RL Am. J. Hum. Genet. 86:45-53(2010). RN [27] RP INVOLVEMENT IN FECD6 AND PPCD3, VARIANT FECD6 HIS-640, CHARACTERIZATION OF RP VARIANTS FECD6 THR-78 AND HIS-640, AND VARIANT GLU-525. RX PubMed=23599324; DOI=10.1167/iovs.13-11781; RA Lechner J., Dash D.P., Muszynska D., Hosseini M., Segev F., George S., RA Frazer D.G., Moore J.E., Kaye S.B., Young T., Simpson D.A., Churchill A.J., RA Heon E., Willoughby C.E.; RT "Mutational spectrum of the ZEB1 gene in corneal dystrophies supports a RT genotype-phenotype correlation."; RL Invest. Ophthalmol. Vis. Sci. 54:3215-3223(2013). RN [28] RP VARIANTS FECD6 THR-78; ALA-649; SER-696; PRO-810; PRO-840 AND GLY-905, RP CHARACTERIZATION OF VARIANTS FECD6 THR-78; ALA-649; SER-696; PRO-810; RP PRO-840 AND GLY-905, AND SUBCELLULAR LOCATION. RX PubMed=25190660; DOI=10.1167/iovs.14-15247; RA Chung D.W., Frausto R.F., Ann L.B., Jang M.S., Aldave A.J.; RT "Functional impact of ZEB1 mutations associated with posterior polymorphous RT and Fuchs' endothelial corneal dystrophies."; RL Invest. Ophthalmol. Vis. Sci. 55:6159-6166(2014). CC -!- FUNCTION: Acts as a transcriptional repressor. Inhibits interleukin-2 CC (IL-2) gene expression. Enhances or represses the promoter activity of CC the ATP1A1 gene depending on the quantity of cDNA and on the cell type. CC Represses E-cadherin promoter and induces an epithelial-mesenchymal CC transition (EMT) by recruiting SMARCA4/BRG1. Represses BCL6 CC transcription in the presence of the corepressor CTBP1. Positively CC regulates neuronal differentiation. Represses RCOR1 transcription CC activation during neurogenesis. Represses transcription by binding to CC the E box (5'-CANNTG-3'). Promotes tumorigenicity by repressing CC stemness-inhibiting microRNAs. {ECO:0000269|PubMed:19935649, CC ECO:0000269|PubMed:20175752, ECO:0000269|PubMed:20418909}. CC -!- SUBUNIT: Interacts (via N-terminus) with SMARCA4/BRG1. CC {ECO:0000269|PubMed:20418909}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20418909, CC ECO:0000269|PubMed:25190660}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=P37275-1; Sequence=Displayed; CC Name=2; CC IsoId=P37275-2; Sequence=VSP_045184; CC Name=3; CC IsoId=P37275-3; Sequence=VSP_047280; CC Name=4; CC IsoId=P37275-4; Sequence=VSP_047281; CC Name=5; CC IsoId=P37275-5; Sequence=VSP_047279, VSP_045184; CC -!- TISSUE SPECIFICITY: Colocalizes with SMARCA4/BRG1 in E-cadherin- CC negative cells from established lines, and stroma of normal colon as CC well as in de-differentiated epithelial cells at the invasion front of CC colorectal carcinomas (at protein level). Expressed in heart and CC skeletal muscle, but not in liver, spleen, or pancreas. CC {ECO:0000269|PubMed:20418909}. CC -!- DISEASE: Corneal dystrophy, posterior polymorphous, 3 (PPCD3) CC [MIM:609141]: A subtype of posterior corneal dystrophy, a disease CC characterized by alterations of Descemet membrane presenting as CC vesicles, opacities or band-like lesions on slit-lamp examination and CC specular microscopy. Affected patient typically are asymptomatic. CC {ECO:0000269|PubMed:16252232, ECO:0000269|PubMed:23599324}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Corneal dystrophy, Fuchs endothelial, 6 (FECD6) [MIM:613270]: CC A corneal disease caused by loss of endothelium of the central cornea. CC It is characterized by focal wart-like guttata that arise from Descemet CC membrane and develop in the central cornea, epithelial blisters, CC reduced vision and pain. Descemet membrane is thickened by abnormal CC collagenous deposition. {ECO:0000269|PubMed:20036349, CC ECO:0000269|PubMed:23599324, ECO:0000269|PubMed:25190660}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the delta-EF1/ZFH-1 C2H2-type zinc-finger CC family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAG62481.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D15050; BAA03646.1; -; mRNA. DR EMBL; U12170; AAA20602.1; -; mRNA. DR EMBL; AK091478; BAC03673.1; -; mRNA. DR EMBL; AK296244; BAG58962.1; -; mRNA. DR EMBL; AK300830; BAG62481.1; ALT_FRAME; mRNA. DR EMBL; AL158080; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL161935; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL117340; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL355148; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471072; EAW85989.1; -; Genomic_DNA. DR EMBL; BC112392; AAI12393.1; -; mRNA. DR EMBL; M81699; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS44370.1; -. [P37275-5] DR CCDS; CCDS53505.1; -. [P37275-2] DR CCDS; CCDS53506.1; -. [P37275-4] DR CCDS; CCDS53507.1; -. [P37275-3] DR CCDS; CCDS7169.1; -. [P37275-1] DR PIR; JX0293; JX0293. DR RefSeq; NP_001121600.1; NM_001128128.2. [P37275-5] DR RefSeq; NP_001167564.1; NM_001174093.1. [P37275-4] DR RefSeq; NP_001167565.1; NM_001174094.1. DR RefSeq; NP_001167566.1; NM_001174095.1. [P37275-3] DR RefSeq; NP_001167567.1; NM_001174096.1. [P37275-2] DR RefSeq; NP_110378.3; NM_030751.5. [P37275-1] DR PDB; 2E19; NMR; -; A=586-642. DR PDBsum; 2E19; -. DR SMR; P37275; -. DR BioGRID; 112796; 42. DR CORUM; P37275; -. DR ELM; P37275; -. DR IntAct; P37275; 8. DR MINT; P37275; -. DR STRING; 9606.ENSP00000354487; -. DR iPTMnet; P37275; -. DR PhosphoSitePlus; P37275; -. DR BioMuta; ZEB1; -. DR DMDM; 6166575; -. DR EPD; P37275; -. DR jPOST; P37275; -. DR MassIVE; P37275; -. DR MaxQB; P37275; -. DR PaxDb; P37275; -. DR PeptideAtlas; P37275; -. DR PRIDE; P37275; -. DR ProteomicsDB; 19473; -. DR ProteomicsDB; 26586; -. DR ProteomicsDB; 55272; -. [P37275-1] DR ProteomicsDB; 61322; -. DR ProteomicsDB; 65678; -. DR Antibodypedia; 12930; 704 antibodies. DR CPTC; P37275; 3 antibodies. DR Ensembl; ENST00000320985; ENSP00000319248; ENSG00000148516. [P37275-1] DR Ensembl; ENST00000361642; ENSP00000354487; ENSG00000148516. [P37275-2] DR Ensembl; ENST00000424869; ENSP00000415961; ENSG00000148516. [P37275-2] DR Ensembl; ENST00000446923; ENSP00000391612; ENSG00000148516. [P37275-5] DR Ensembl; ENST00000542815; ENSP00000444891; ENSG00000148516. [P37275-3] DR Ensembl; ENST00000560721; ENSP00000452787; ENSG00000148516. [P37275-4] DR GeneID; 6935; -. DR KEGG; hsa:6935; -. DR UCSC; uc001ivs.5; human. [P37275-1] DR CTD; 6935; -. DR DisGeNET; 6935; -. DR GeneCards; ZEB1; -. DR HGNC; HGNC:11642; ZEB1. DR HPA; ENSG00000148516; Low tissue specificity. DR MalaCards; ZEB1; -. DR MIM; 189909; gene. DR MIM; 609141; phenotype. DR MIM; 613270; phenotype. DR neXtProt; NX_P37275; -. DR OpenTargets; ENSG00000148516; -. DR Orphanet; 98974; Fuchs endothelial corneal dystrophy. DR Orphanet; 98973; Posterior polymorphous corneal dystrophy. DR PharmGKB; PA162409589; -. DR VEuPathDB; HostDB:ENSG00000148516.21; -. DR eggNOG; KOG3623; Eukaryota. DR GeneTree; ENSGT00950000183208; -. DR HOGENOM; CLU_005890_0_1_1; -. DR InParanoid; P37275; -. DR OMA; WDRVKED; -. DR OrthoDB; 890458at2759; -. DR PhylomeDB; P37275; -. DR TreeFam; TF331759; -. DR PathwayCommons; P37275; -. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR SignaLink; P37275; -. DR SIGNOR; P37275; -. DR BioGRID-ORCS; 6935; 27 hits in 1019 CRISPR screens. DR ChiTaRS; ZEB1; human. DR EvolutionaryTrace; P37275; -. DR GeneWiki; ZEB1; -. DR GenomeRNAi; 6935; -. DR Pharos; P37275; Tbio. DR PRO; PR:P37275; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; P37275; protein. DR Bgee; ENSG00000148516; Expressed in calcaneal tendon and 248 other tissues. DR ExpressionAtlas; P37275; baseline and differential. DR Genevisible; P37275; HS. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:ProtInc. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:BHF-UCL. DR GO; GO:0070888; F:E-box binding; ISS:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc. DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central. DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome. DR GO; GO:0045602; P:negative regulation of endothelial cell differentiation; IMP:BHF-UCL. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW. DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR CDD; cd00086; homeodomain; 1. DR InterPro; IPR008598; Di19_Zn-bd. DR InterPro; IPR009057; Homeobox-like_sf. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR036236; Znf_C2H2_sf. DR InterPro; IPR013087; Znf_C2H2_type. DR Pfam; PF00096; zf-C2H2; 4. DR Pfam; PF05605; zf-Di19; 1. DR SMART; SM00389; HOX; 1. DR SMART; SM00355; ZnF_C2H2; 7. DR SUPFAM; SSF46689; SSF46689; 1. DR SUPFAM; SSF57667; SSF57667; 4. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 5. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 6. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Corneal dystrophy; KW Differentiation; Disease variant; DNA-binding; Homeobox; Isopeptide bond; KW Metal-binding; Neurogenesis; Nucleus; Phosphoprotein; Reference proteome; KW Repeat; Repressor; Transcription; Transcription regulation; KW Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1..1124 FT /note="Zinc finger E-box-binding homeobox 1" FT /id="PRO_0000047231" FT ZN_FING 170..193 FT /note="C2H2-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 200..222 FT /note="C2H2-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 240..262 FT /note="C2H2-type 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 268..292 FT /note="C2H2-type 4; atypical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT DNA_BIND 581..640 FT /note="Homeobox; atypical" FT ZN_FING 904..926 FT /note="C2H2-type 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 932..954 FT /note="C2H2-type 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 960..981 FT /note="C2H2-type 7; atypical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT COMPBIAS 989..1124 FT /note="Glu-rich (acidic)" FT MOD_RES 31 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q62947" FT MOD_RES 33 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q62947" FT MOD_RES 313 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q64318" FT MOD_RES 322 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 642 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 679 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 686 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q64318" FT MOD_RES 693 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q64318" FT MOD_RES 700 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q64318" FT MOD_RES 702 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 704 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q64318" FT CROSSLNK 186 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 195 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 307 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 331 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 335 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 347 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO); alternate" FT CROSSLNK 347 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 439 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 493 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25114211, FT ECO:0007744|PubMed:25218447, ECO:0007744|PubMed:25755297, FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733" FT CROSSLNK 504 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 515 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 548 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 553 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 774 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO); alternate" FT CROSSLNK 774 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..19 FT /note="MADGPRCKRRKQANPRRNN -> MK (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_047279" FT VAR_SEQ 20..87 FT /note="VTNYNTVVETNSDSDDEDKLHIVEEESVTDAADCEGVPEDDLPTDQTVLPGR FT SSEREGNAKNCWEDDR -> G (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_047280" FT VAR_SEQ 87..107 FT /note="RKEGQEILGPEAQADEAGCTV -> I (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_047281" FT VAR_SEQ 87 FT /note="R -> TG (in isoform 2 and isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_045184" FT VARIANT 78 FT /note="N -> T (in FECD6; no effect on protein expression; FT no effect on nuclear localization; dbSNP:rs80194531)" FT /evidence="ECO:0000269|PubMed:20036349, FT ECO:0000269|PubMed:23599324, ECO:0000269|PubMed:25190660" FT /id="VAR_063759" FT VARIANT 90 FT /note="G -> R (in dbSNP:rs12217419)" FT /id="VAR_052731" FT VARIANT 525 FT /note="G -> E (found in a patient with FECD6)" FT /evidence="ECO:0000269|PubMed:23599324" FT /id="VAR_072897" FT VARIANT 553 FT /note="K -> R (in dbSNP:rs35753967)" FT /id="VAR_031824" FT VARIANT 640 FT /note="Q -> H (in FECD6; down-regulation of several FT collagen genes expression; dbSNP:rs779148597)" FT /evidence="ECO:0000269|PubMed:23599324" FT /id="VAR_072898" FT VARIANT 649 FT /note="P -> A (in FECD6; no effect on protein expression; FT no effect on nuclear localization; dbSNP:rs781750314)" FT /evidence="ECO:0000269|PubMed:20036349, FT ECO:0000269|PubMed:25190660" FT /id="VAR_063760" FT VARIANT 696 FT /note="N -> S (in FECD6; no effect on protein expression; FT no effect on nuclear localization; dbSNP:rs567252241)" FT /evidence="ECO:0000269|PubMed:25190660" FT /id="VAR_072899" FT VARIANT 810 FT /note="Q -> P (in FECD6; no effect on protein expression; FT no effect on nuclear localization; dbSNP:rs199944415)" FT /evidence="ECO:0000269|PubMed:20036349, FT ECO:0000269|PubMed:25190660" FT /id="VAR_063761" FT VARIANT 840 FT /note="Q -> P (in FECD6; no effect on protein expression; FT no effect on nuclear localization; dbSNP:rs118020901)" FT /evidence="ECO:0000269|PubMed:20036349, FT ECO:0000269|PubMed:25190660" FT /id="VAR_063762" FT VARIANT 905 FT /note="A -> G (in FECD6; no effect on protein expression; FT no effect on nuclear localization; dbSNP:rs78449005)" FT /evidence="ECO:0000269|PubMed:25190660" FT /id="VAR_072900" FT VARIANT 905 FT /note="A -> T (in FECD6)" FT /evidence="ECO:0000269|PubMed:20036349" FT /id="VAR_063763" FT CONFLICT 12 FT /note="Q -> R (in Ref. 3; BAC03673)" FT /evidence="ECO:0000305" FT CONFLICT 81 FT /note="N -> S (in Ref. 3; BAC03673)" FT /evidence="ECO:0000305" FT CONFLICT 84 FT /note="E -> K (in Ref. 3; BAC03673)" FT /evidence="ECO:0000305" FT CONFLICT 220 FT /note="T -> A (in Ref. 3; BAG62481)" FT /evidence="ECO:0000305" FT CONFLICT 390 FT /note="M -> T (in Ref. 3; BAG62481)" FT /evidence="ECO:0000305" FT CONFLICT 420 FT /note="V -> I (in Ref. 2; AAA20602)" FT /evidence="ECO:0000305" FT CONFLICT 472 FT /note="K -> R (in Ref. 3; BAG58962)" FT /evidence="ECO:0000305" FT CONFLICT 609 FT /note="E -> Q (in Ref. 7; M81699)" FT /evidence="ECO:0000305" FT CONFLICT 654 FT /note="I -> T (in Ref. 2; AAA20602)" FT /evidence="ECO:0000305" FT CONFLICT 672 FT /note="D -> H (in Ref. 7; M81699)" FT /evidence="ECO:0000305" FT CONFLICT 681 FT /note="L -> S (in Ref. 7; M81699)" FT /evidence="ECO:0000305" FT CONFLICT 775 FT /note="K -> T (in Ref. 3; BAG62481)" FT /evidence="ECO:0000305" FT CONFLICT 793..794 FT /note="IP -> KY (in Ref. 3; BAG58962)" FT /evidence="ECO:0000305" FT CONFLICT 797 FT /note="A -> N (in Ref. 3; BAG58962)" FT /evidence="ECO:0000305" FT CONFLICT 818 FT /note="A -> V (in Ref. 3; BAG62481)" FT /evidence="ECO:0000305" FT CONFLICT 838 FT /note="I -> T (in Ref. 3; BAC03673)" FT /evidence="ECO:0000305" FT CONFLICT 1066 FT /note="E -> G (in Ref. 3; BAC03673)" FT /evidence="ECO:0000305" FT HELIX 590..600 FT /evidence="ECO:0007744|PDB:2E19" FT HELIX 608..618 FT /evidence="ECO:0007744|PDB:2E19" FT HELIX 622..634 FT /evidence="ECO:0007744|PDB:2E19" SQ SEQUENCE 1124 AA; 124074 MW; 0A2714CC37C848D1 CRC64; MADGPRCKRR KQANPRRNNV TNYNTVVETN SDSDDEDKLH IVEEESVTDA ADCEGVPEDD LPTDQTVLPG RSSEREGNAK NCWEDDRKEG QEILGPEAQA DEAGCTVKDD ECESDAENEQ NHDPNVEEFL QQQDTAVIFP EAPEEDQRQG TPEASGHDEN GTPDAFSQLL TCPYCDRGYK RFTSLKEHIK YRHEKNEDNF SCSLCSYTFA YRTQLERHMT SHKSGRDQRH VTQSGCNRKF KCTECGKAFK YKHHLKEHLR IHSGEKPYEC PNCKKRFSHS GSYSSHISSK KCISLIPVNG RPRTGLKTSQ CSSPSLSASP GSPTRPQIRQ KIENKPLQEQ LSVNQIKTEP VDYEFKPIVV ASGINCSTPL QNGVFTGGGP LQATSSPQGM VQAVVLPTVG LVSPISINLS DIQNVLKVAV DGNVIRQVLE NNQANLASKE QETINASPIQ QGGHSVISAI SLPLVDQDGT TKIIINYSLE QPSQLQVVPQ NLKKENPVAT NSCKSEKLPE DLTVKSEKDK SFEGGVNDST CLLCDDCPGD INALPELKHY DLKQPTQPPP LPAAEAEKPE SSVSSATGDG NLSPSQPPLK NLLSLLKAYY ALNAQPSAEE LSKIADSVNL PLDVVKKWFE KMQAGQISVQ SSEPSSPEPG KVNIPAKNND QPQSANANEP QDSTVNLQSP LKMTNSPVLP VGSTTNGSRS STPSPSPLNL SSSRNTQGYL YTAEGAQEEP QVEPLDLSLP KQQGELLERS TITSVYQNSV YSVQEEPLNL SCAKKEPQKD SCVTDSEPVV NVIPPSANPI NIAIPTVTAQ LPTIVAIADQ NSVPCLRALA ANKQTILIPQ VAYTYSTTVS PAVQEPPLKV IQPNGNQDER QDTSSEGVSN VEDQNDSDST PPKKKMRKTE NGMYACDLCD KIFQKSSSLL RHKYEHTGKR PHECGICKKA FKHKHHLIEH MRLHSGEKPY QCDKCGKRFS HSGSYSQHMN HRYSYCKREA EERDSTEQEE AGPEILSNEH VGARASPSQG DSDERESLTR EEDEDSEKEE EEEDKEMEEL QEEKECEKPQ GDEEEEEEEE EVEEEEVEEA ENEGEEAKTE GLMKDDRAES QASSLGQKVG ESSEQVSEEK TNEA //