ZEB2_HUMAN
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 03-AUG-2022, entry version 220.
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},
GN SIP1 {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; 62.
DR CORUM; O60315; -.
DR ELM; O60315; -.
DR IntAct; O60315; 54.
DR MINT; O60315; -.
DR STRING; 9606.ENSP00000454157; -.
DR iPTMnet; O60315; -.
DR PhosphoSitePlus; O60315; -.
DR BioMuta; ZEB2; -.
DR EPD; O60315; -.
DR jPOST; O60315; -.
DR MassIVE; O60315; -.
DR MaxQB; O60315; -.
DR PaxDb; O60315; -.
DR PeptideAtlas; O60315; -.
DR PRIDE; O60315; -.
DR ProteomicsDB; 27650; -.
DR ProteomicsDB; 49342; -. [O60315-1]
DR Antibodypedia; 18810; 673 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 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; IATPFSC; -.
DR OrthoDB; 890458at2759; -.
DR PhylomeDB; O60315; -.
DR TreeFam; TF331759; -.
DR PathwayCommons; O60315; -.
DR SignaLink; O60315; -.
DR SIGNOR; O60315; -.
DR BioGRID-ORCS; 9839; 113 hits in 1114 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 203 other tissues.
DR ExpressionAtlas; O60315; baseline and differential.
DR Genevisible; O60315; HS.
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; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0048066; P:developmental pigmentation; ISS:BHF-UCL.
DR GO; GO:0097324; P:melanocyte migration; ISS:BHF-UCL.
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: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:1903056; P:regulation of melanosome organization; ISS:BHF-UCL.
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; 3.
DR Pfam; PF05605; zf-Di19; 1.
DR SMART; SM00389; HOX; 1.
DR SMART; SM00355; ZnF_C2H2; 8.
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; 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
