ID   ZEB2_HUMAN              Reviewed;        1214 AA.
AC   O60315; A0JP09; B7Z2P2; F5H814; Q9UED1;
DT   21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1998, sequence version 1.
DT   27-MAR-2024, entry version 229.
DE   RecName: Full=Zinc finger E-box-binding homeobox 2;
DE   AltName: Full=Smad-interacting protein 1 {ECO:0000303|PubMed:11448942};
DE            Short=SMADIP1 {ECO:0000303|PubMed:11448942};
DE   AltName: Full=Zinc finger homeobox protein 1b;
GN   Name=ZEB2 {ECO:0000312|HGNC:HGNC:14881};
GN   Synonyms=KIAA0569 {ECO:0000303|PubMed:9628581}, SIP1
GN   {ECO:0000303|PubMed:11448942}, ZFHX1B, ZFX1B; ORFNames=HRIHFB2411;
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 [GENOMIC DNA], AND INVOLVEMENT IN MOWS.
RX   PubMed=11448942; DOI=10.1093/hmg/10.14.1503;
RA   Cacheux V., Dastot-Le Moal F., Kaeaeriaeinen H., Bondurand N., Rintala R.,
RA   Boissier B., Wilson M., Mowat D., Goossens M.;
RT   "Loss-of-function mutations in SIP1 Smad interacting protein 1 result in a
RT   syndromic Hirschsprung disease.";
RL   Hum. Mol. Genet. 10:1503-1510(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=11279515; DOI=10.1038/86860;
RA   Wakamatsu N., Yamada Y., Yamada K., Ono T., Nomura N., Taniguchi H.,
RA   Kitoh H., Mutoh N., Yamanaka T., Mushiake K., Kato K., Sonta S., Nagaya M.;
RT   "Mutations in SIP1, encoding Smad interacting protein 1, cause a form of
RT   Hirschsprung disease.";
RL   Nat. Genet. 27:369-370(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA   Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA   Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. IX. The
RT   complete sequences of 100 new cDNA clones from brain which can code for
RT   large proteins in vitro.";
RL   DNA Res. 5:31-39(1998).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Brain;
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [LARGE SCALE MRNA] OF 1161-1214 (ISOFORM 1), AND
RP   SUBCELLULAR LOCATION.
RC   TISSUE=Fetal brain;
RX   PubMed=9853615; DOI=10.1038/4315;
RA   Ueki N., Oda T., Kondo M., Yano K., Noguchi T., Muramatsu M.-A.;
RT   "Selection system for genes encoding nuclear-targeted proteins.";
RL   Nat. Biotechnol. 16:1338-1342(1998).
RN   [8]
RP   FUNCTION, SUMOYLATION AT LYS-391 AND LYS-866, INTERACTION WITH CBX4 AND
RP   CTBP1, AND SUBCELLULAR LOCATION.
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   [9]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-377, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA   Olsen J.V., Mann M.;
RT   "Lysine acetylation targets protein complexes and co-regulates major
RT   cellular functions.";
RL   Science 325:834-840(2009).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-142; SER-360; SER-647;
RP   THR-782; SER-784 AND SER-1122, AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RC   TISSUE=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   [11]
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   [12]
RP   SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-391 AND LYS-866, 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   [13]
RP   SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-391, AND IDENTIFICATION BY MASS
RP   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   [14]
RP   SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-391; LYS-479; LYS-555; LYS-611;
RP   LYS-632; LYS-713 AND LYS-866, AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [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   [15]
RP   STRUCTURE BY NMR OF 647-705.
RG   RIKEN structural genomics initiative (RSGI);
RT   "Solution structure of the homeobox domain of zinc finger homeobox protein
RT   1B (SMAD interacting protein 1).";
RL   Submitted (DEC-2006) to the PDB data bank.
RN   [16]
RP   VARIANT MOWS ASN-99 DEL.
RX   PubMed=12451214; DOI=10.1212/01.wnl.0000034842.78350.4e;
RA   Yoneda M., Fujita T., Yamada Y., Yamada K., Fujii A., Inagaki T.,
RA   Nakagawa H., Shimada A., Kishikawa M., Nagaya M., Azuma T., Kuriyama M.,
RA   Wakamatsu N.;
RT   "Late infantile Hirschsprung disease-mental retardation syndrome with a 3-
RT   bp deletion in ZFHX1B.";
RL   Neurology 59:1637-1640(2002).
RN   [17]
RP   VARIANT MOWS GLY-953.
RX   PubMed=15384097; DOI=10.1002/ajmg.a.30312;
RA   Gregory-Evans C.Y., Vieira H., Dalton R., Adams G.G.W., Salt A.,
RA   Gregory-Evans K.;
RT   "Ocular coloboma and high myopia with Hirschsprung disease associated with
RT   a novel ZFHX1B missense mutation and trisomy 21.";
RL   Am. J. Med. Genet. A 131:86-90(2004).
RN   [18]
RP   VARIANT MOWS ARG-1119.
RX   PubMed=16688751; DOI=10.1002/ajmg.a.31267;
RA   Heinritz W., Zweier C., Froster U.G., Strenge S., Kujat A., Syrbe S.,
RA   Rauch A., Schuster V.;
RT   "A missense mutation in the ZFHX1B gene associated with an atypical Mowat-
RT   Wilson syndrome phenotype.";
RL   Am. J. Med. Genet. A 140:1223-1227(2006).
RN   [19]
RP   VARIANT [LARGE SCALE ANALYSIS] ASN-983.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
RN   [20]
RP   FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RX   PubMed=20516212; DOI=10.1128/mcb.01237-09;
RA   Chen Y., Banda M., Speyer C.L., Smith J.S., Rabson A.B., Gorski D.H.;
RT   "Regulation of the expression and activity of the antiangiogenic homeobox
RT   gene GAX/MEOX2 by ZEB2 and microRNA-221.";
RL   Mol. Cell. Biol. 30:3902-3913(2010).
CC   -!- FUNCTION: Transcriptional inhibitor that binds to DNA sequence 5'-
CC       CACCT-3' in different promoters (PubMed:16061479, PubMed:20516212).
CC       Represses transcription of E-cadherin (PubMed:16061479). Represses
CC       expression of MEOX2 (PubMed:20516212). {ECO:0000269|PubMed:16061479,
CC       ECO:0000269|PubMed:20516212}.
CC   -!- SUBUNIT: Binds activated SMAD1, activated SMAD2 and activated SMAD3;
CC       binding with SMAD4 is not detected (By similarity). Interacts with CBX4
CC       and CTBP1. {ECO:0000250, ECO:0000269|PubMed:16061479}.
CC   -!- INTERACTION:
CC       O60315; Q96KQ7: EHMT2; NbExp=6; IntAct=EBI-717614, EBI-744366;
CC       O60315; Q13330: MTA1; NbExp=12; IntAct=EBI-717614, EBI-714236;
CC       O60315; O94776: MTA2; NbExp=4; IntAct=EBI-717614, EBI-1783035;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16061479,
CC       ECO:0000269|PubMed:9853615}. Chromosome {ECO:0000269|PubMed:20516212}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=O60315-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O60315-2; Sequence=VSP_044797;
CC   -!- INDUCTION: Down-regulated by microRNA-221 (miR-221).
CC       {ECO:0000269|PubMed:20516212}.
CC   -!- PTM: Sumoylation on Lys-391 and Lys-866 is promoted by the E3 SUMO-
CC       protein ligase CBX4, and impairs interaction with CTBP1 and
CC       transcription repression activity. {ECO:0000269|PubMed:16061479}.
CC   -!- DISEASE: Mowat-Wilson syndrome (MOWS) [MIM:235730]: A complex
CC       developmental disorder characterized by intellectual disability,
CC       delayed motor development, epilepsy, microcephaly and a wide spectrum
CC       of clinically heterogeneous features suggestive of neurocristopathies
CC       at the cephalic, cardiac, and vagal levels. Affected patients show an
CC       easily recognizable facial appearance with deep set eyes and
CC       hypertelorism, medially divergent, broad eyebrows, prominent columella,
CC       pointed chin and uplifted, notched ear lobes. Some patients manifest
CC       Hirschsprung disease. {ECO:0000269|PubMed:11448942,
CC       ECO:0000269|PubMed:12451214, ECO:0000269|PubMed:15384097,
CC       ECO:0000269|PubMed:16688751}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the delta-EF1/ZFH-1 C2H2-type zinc-finger
CC       family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA25495.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AY029472; AAK52081.1; -; Genomic_DNA.
DR   EMBL; AB056507; BAB40819.1; -; mRNA.
DR   EMBL; AB011141; BAA25495.2; ALT_INIT; mRNA.
DR   EMBL; AK294928; BAH11928.1; -; mRNA.
DR   EMBL; AC009951; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC010130; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC127102; AAI27103.1; -; mRNA.
DR   EMBL; AB015341; BAA34798.1; -; mRNA.
DR   CCDS; CCDS2186.1; -. [O60315-1]
DR   CCDS; CCDS54403.1; -. [O60315-2]
DR   RefSeq; NP_001165124.1; NM_001171653.1. [O60315-2]
DR   RefSeq; NP_055610.1; NM_014795.3. [O60315-1]
DR   RefSeq; XP_006712944.1; XM_006712881.3.
DR   RefSeq; XP_006712945.1; XM_006712882.3.
DR   PDB; 2DA7; NMR; -; A=647-704.
DR   PDBsum; 2DA7; -.
DR   AlphaFoldDB; O60315; -.
DR   BMRB; O60315; -.
DR   SMR; O60315; -.
DR   BioGRID; 115175; 71.
DR   CORUM; O60315; -.
DR   ELM; O60315; -.
DR   IntAct; O60315; 54.
DR   MINT; O60315; -.
DR   STRING; 9606.ENSP00000487174; -.
DR   iPTMnet; O60315; -.
DR   PhosphoSitePlus; O60315; -.
DR   BioMuta; ZEB2; -.
DR   EPD; O60315; -.
DR   jPOST; O60315; -.
DR   MassIVE; O60315; -.
DR   MaxQB; O60315; -.
DR   PaxDb; 9606-ENSP00000454157; -.
DR   PeptideAtlas; O60315; -.
DR   ProteomicsDB; 27650; -.
DR   ProteomicsDB; 49342; -. [O60315-1]
DR   Pumba; O60315; -.
DR   Antibodypedia; 18810; 763 antibodies from 41 providers.
DR   CPTC; O60315; 1 antibody.
DR   DNASU; 9839; -.
DR   Ensembl; ENST00000409487.7; ENSP00000386854.2; ENSG00000169554.23. [O60315-1]
DR   Ensembl; ENST00000539609.7; ENSP00000443792.2; ENSG00000169554.23. [O60315-2]
DR   Ensembl; ENST00000558170.6; ENSP00000454157.1; ENSG00000169554.23. [O60315-1]
DR   Ensembl; ENST00000627532.3; ENSP00000487174.1; ENSG00000169554.23. [O60315-1]
DR   GeneID; 9839; -.
DR   KEGG; hsa:9839; -.
DR   MANE-Select; ENST00000627532.3; ENSP00000487174.1; NM_014795.4; NP_055610.1.
DR   UCSC; uc002tvu.4; human. [O60315-1]
DR   AGR; HGNC:14881; -.
DR   CTD; 9839; -.
DR   DisGeNET; 9839; -.
DR   GeneCards; ZEB2; -.
DR   GeneReviews; ZEB2; -.
DR   HGNC; HGNC:14881; ZEB2.
DR   HPA; ENSG00000169554; Tissue enhanced (brain).
DR   MalaCards; ZEB2; -.
DR   MIM; 235730; phenotype.
DR   MIM; 605802; gene.
DR   neXtProt; NX_O60315; -.
DR   OpenTargets; ENSG00000169554; -.
DR   Orphanet; 261552; Mowat-Wilson syndrome due to a ZEB2 point mutation.
DR   Orphanet; 261537; Mowat-Wilson syndrome due to monosomy 2q22.
DR   PharmGKB; PA162409612; -.
DR   VEuPathDB; HostDB:ENSG00000169554; -.
DR   eggNOG; KOG3623; Eukaryota.
DR   GeneTree; ENSGT00950000183208; -.
DR   HOGENOM; CLU_005890_0_1_1; -.
DR   InParanoid; O60315; -.
DR   OMA; QENMFTP; -.
DR   OrthoDB; 4266655at2759; -.
DR   PhylomeDB; O60315; -.
DR   TreeFam; TF331759; -.
DR   PathwayCommons; O60315; -.
DR   Reactome; R-HSA-9762293; Regulation of CDH11 gene transcription.
DR   Reactome; R-HSA-9823739; Formation of the anterior neural plate.
DR   Reactome; R-HSA-9832991; Formation of the posterior neural plate.
DR   SignaLink; O60315; -.
DR   SIGNOR; O60315; -.
DR   BioGRID-ORCS; 9839; 123 hits in 1200 CRISPR screens.
DR   ChiTaRS; ZEB2; human.
DR   EvolutionaryTrace; O60315; -.
DR   GeneWiki; ZEB2; -.
DR   GenomeRNAi; 9839; -.
DR   Pharos; O60315; Tbio.
DR   PRO; PR:O60315; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; O60315; Protein.
DR   Bgee; ENSG00000169554; Expressed in cortical plate and 204 other cell types or tissues.
DR   ExpressionAtlas; O60315; baseline and differential.
DR   GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005730; C:nucleolus; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0019208; F:phosphatase regulator activity; NAS:UniProtKB.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR   GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR   GO; GO:0048143; P:astrocyte activation; IEA:Ensembl.
DR   GO; GO:0048066; P:developmental pigmentation; ISS:BHF-UCL.
DR   GO; GO:0043542; P:endothelial cell migration; IEA:Ensembl.
DR   GO; GO:0001935; P:endothelial cell proliferation; IEA:Ensembl.
DR   GO; GO:0072537; P:fibroblast activation; IEA:Ensembl.
DR   GO; GO:0097324; P:melanocyte migration; ISS:BHF-UCL.
DR   GO; GO:0036446; P:myofibroblast differentiation; IEA:Ensembl.
DR   GO; GO:0010764; P:negative regulation of fibroblast migration; IEA:Ensembl.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR   GO; GO:0007399; P:nervous system development; NAS:UniProtKB.
DR   GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:DIBU.
DR   GO; GO:0048023; P:positive regulation of melanin biosynthetic process; IC:BHF-UCL.
DR   GO; GO:0045636; P:positive regulation of melanocyte differentiation; ISS:BHF-UCL.
DR   GO; GO:1904330; P:positive regulation of myofibroblast contraction; IEA:Ensembl.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR   GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IMP:DIBU.
DR   GO; GO:0070269; P:pyroptosis; IEA:Ensembl.
DR   GO; GO:1905603; P:regulation of blood-brain barrier permeability; IEA:Ensembl.
DR   GO; GO:1903056; P:regulation of melanosome organization; ISS:BHF-UCL.
DR   GO; GO:1904520; P:regulation of myofibroblast cell apoptotic process; IEA:Ensembl.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0090649; P:response to oxygen-glucose deprivation; IEA:Ensembl.
DR   GO; GO:0043149; P:stress fiber assembly; IEA:Ensembl.
DR   Gene3D; 3.30.160.60; Classic Zinc Finger; 6.
DR   Gene3D; 1.10.10.60; Homeodomain-like; 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   PANTHER; PTHR24391; HISTONE H4 TRANSCRIPTION FACTOR-RELATED; 1.
DR   PANTHER; PTHR24391:SF18; ZINC FINGER PROTEIN 1; 1.
DR   Pfam; PF00096; zf-C2H2; 3.
DR   Pfam; PF05605; zf-Di19; 1.
DR   Pfam; PF12874; zf-met; 1.
DR   SMART; SM00389; HOX; 1.
DR   SMART; SM00355; ZnF_C2H2; 8.
DR   SUPFAM; SSF57667; beta-beta-alpha zinc fingers; 4.
DR   SUPFAM; SSF46689; Homeodomain-like; 1.
DR   PROSITE; PS00028; ZINC_FINGER_C2H2_1; 5.
DR   PROSITE; PS50157; ZINC_FINGER_C2H2_2; 6.
DR   Genevisible; O60315; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Alternative splicing; Chromosome;
KW   Disease variant; DNA-binding; Epilepsy; Hirschsprung disease; Homeobox;
KW   Intellectual disability; Isopeptide bond; Metal-binding; Nucleus;
KW   Phosphoprotein; Reference proteome; Repeat; Repressor; Transcription;
KW   Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT   CHAIN           1..1214
FT                   /note="Zinc finger E-box-binding homeobox 2"
FT                   /id="PRO_0000047236"
FT   ZN_FING         211..234
FT                   /note="C2H2-type 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         241..263
FT                   /note="C2H2-type 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         282..304
FT                   /note="C2H2-type 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         310..334
FT                   /note="C2H2-type 4; atypical"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         581..605
FT                   /note="C2H2-type 5; atypical"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   DNA_BIND        644..703
FT                   /note="Homeobox; atypical"
FT   ZN_FING         999..1021
FT                   /note="C2H2-type 6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         1027..1049
FT                   /note="C2H2-type 7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         1055..1076
FT                   /note="C2H2-type 8; atypical"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   REGION          1..101
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          437..487
FT                   /note="SMAD-MH2 binding domain"
FT                   /evidence="ECO:0000250"
FT   REGION          702..740
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          771..810
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          832..857
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1117..1214
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        37..52
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        57..74
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        78..96
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        702..726
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        778..810
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        833..857
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1125..1156
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1157..1171
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1172..1214
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         142
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         356
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9R0G7"
FT   MOD_RES         360
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         364
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9R0G7"
FT   MOD_RES         377
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:19608861"
FT   MOD_RES         647
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         731
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9R0G7"
FT   MOD_RES         780
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9R0G7"
FT   MOD_RES         782
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         784
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         1122
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         1124
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9R0G7"
FT   MOD_RES         1203
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9R0G7"
FT   CROSSLNK        391
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO); alternate"
FT   CROSSLNK        391
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2); alternate"
FT                   /evidence="ECO:0007744|PubMed:25218447,
FT                   ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733"
FT   CROSSLNK        479
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0007744|PubMed:28112733"
FT   CROSSLNK        555
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0007744|PubMed:28112733"
FT   CROSSLNK        611
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0007744|PubMed:28112733"
FT   CROSSLNK        632
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0007744|PubMed:28112733"
FT   CROSSLNK        713
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0007744|PubMed:28112733"
FT   CROSSLNK        866
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO); alternate"
FT   CROSSLNK        866
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2); alternate"
FT                   /evidence="ECO:0007744|PubMed:25218447,
FT                   ECO:0007744|PubMed:28112733"
FT   VAR_SEQ         111..134
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_044797"
FT   VARIANT         99
FT                   /note="Missing (in MOWS)"
FT                   /evidence="ECO:0000269|PubMed:12451214"
FT                   /id="VAR_027016"
FT   VARIANT         953
FT                   /note="R -> G (in MOWS)"
FT                   /evidence="ECO:0000269|PubMed:15384097"
FT                   /id="VAR_027017"
FT   VARIANT         983
FT                   /note="D -> N (in a colorectal cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_035563"
FT   VARIANT         1119
FT                   /note="Q -> R (in MOWS; dbSNP:rs137852983)"
FT                   /evidence="ECO:0000269|PubMed:16688751"
FT                   /id="VAR_027018"
FT   CONFLICT        1155
FT                   /note="D -> G (in Ref. 4; BAH11928)"
FT                   /evidence="ECO:0000305"
FT   HELIX           654..665
FT                   /evidence="ECO:0007829|PDB:2DA7"
FT   HELIX           671..681
FT                   /evidence="ECO:0007829|PDB:2DA7"
FT   HELIX           685..700
FT                   /evidence="ECO:0007829|PDB:2DA7"
SQ   SEQUENCE   1214 AA;  136447 MW;  B578FD91339C3FDD CRC64;
     MKQPIMADGP RCKRRKQANP RRKNVVNYDN VVDTGSETDE EDKLHIAEDD GIANPLDQET
     SPASVPNHES SPHVSQALLP REEEEDEIRE GGVEHPWHNN EILQASVDGP EEMKEDYDTM
     GPEATIQTAI NNGTVKNANC TSDFEEYFAK RKLEERDGHA VSIEEYLQRS DTAIIYPEAP
     EELSRLGTPE ANGQEENDLP PGTPDAFAQL LTCPYCDRGY KRLTSLKEHI KYRHEKNEEN
     FSCPLCSYTF AYRTQLERHM VTHKPGTDQH QMLTQGAGNR KFKCTECGKA FKYKHHLKEH
     LRIHSGEKPY ECPNCKKRFS HSGSYSSHIS SKKCIGLISV NGRMRNNIKT GSSPNSVSSS
     PTNSAITQLR NKLENGKPLS MSEQTGLLKI KTEPLDFNDY KVLMATHGFS GTSPFMNGGL
     GATSPLGVHP SAQSPMQHLG VGMEAPLLGF PTMNSNLSEV QKVLQIVDNT VSRQKMDCKA
     EEISKLKGYH MKDPCSQPEE QGVTSPNIPP VGLPVVSHNG ATKSIIDYTL EKVNEAKACL
     QSLTTDSRRQ ISNIKKEKLR TLIDLVTDDK MIENHNISTP FSCQFCKESF PGPIPLHQHE
     RYLCKMNEEI KAVLQPHENI VPNKAGVFVD NKALLLSSVL SEKGMTSPIN PYKDHMSVLK
     AYYAMNMEPN SDELLKISIA VGLPQEFVKE WFEQRKVYQY SNSRSPSLER SSKPLAPNSN
     PPTKDSLLPR SPVKPMDSIT SPSIAELHNS VTNCDPPLRL TKPSHFTNIK PVEKLDHSRS
     NTPSPLNLSS TSSKNSHSSS YTPNSFSSEE LQAEPLDLSL PKQMKEPKSI IATKNKTKAS
     SISLDHNSVS SSSENSDEPL NLTFIKKEFS NSNNLDNKST NPVFSMNPFS AKPLYTALPP
     QSAFPPATFM PPVQTSIPGL RPYPGLDQMS FLPHMAYTYP TGAATFADMQ QRRKYQRKQG
     FQGELLDGAQ DYMSGLDDMT DSDSCLSRKK IKKTESGMYA CDLCDKTFQK SSSLLRHKYE
     HTGKRPHQCQ ICKKAFKHKH HLIEHSRLHS GEKPYQCDKC GKRFSHSGSY SQHMNHRYSY
     CKREAEEREA AEREAREKGH LEPTELLMNR AYLQSITPQG YSDSEERESM PRDGESEKEH
     EKEGEDGYGK LGRQDGDEEF EEEEEESENK SMDTDPETIR DEEETGDHSM DDSSEDGKME
     TKSDHEEDNM EDGM
//