ZEB1 Available structures PDB Ortholog search: PDBe RCSB
Identifiers Aliases ZEB1 , zinc finger E-box binding homeobox 1, AREB6, BZP, DELTAEF1, FECD6, NIL2A, PPCD3, TCF8, ZFHEP, ZFHX1AExternal IDs OMIM : 189909 MGI : 1344313 HomoloGene : 31779 GeneCards : ZEB1 show Gene location (Human )Chr. Chromosome 10 (human) [1] Band 10p11.22 Start 31,318,495 bp [1] End 31,529,814 bp [1]
show Gene location (Mouse )Chr. Chromosome 18 (mouse)[2] Band 18 4.42 cM|18 A1 Start 5,591,860 bp [2] End 5,775,467 bp [2]
show Gene ontology Molecular function • DNA binding • GO:0001106 transcription corepressor activity • GO:0001105 transcription coactivator activity • zinc ion binding • transcription factor binding • chromatin binding • metal ion binding • GO:0001948 protein binding • nucleic acid binding • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • E-box binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component • transcription regulator complex • nucleus • nucleoplasm • cytosol Biological process • pattern specification process • embryonic skeletal system morphogenesis • regulation of smooth muscle cell differentiation • animal organ development • cell differentiation • semicircular canal morphogenesis • regulation of transcription, DNA-templated • regulation of transcription by RNA polymerase II • transcription, DNA-templated • nervous system development • regulation of transforming growth factor beta receptor signaling pathway • regulation of T cell differentiation in thymus • central nervous system development • cartilage development • regulation of mesenchymal cell proliferation • embryonic camera-type eye morphogenesis • cochlea morphogenesis • immune response • embryonic morphogenesis • cellular response to amino acid stimulus • cell population proliferation • negative regulation of epithelial cell differentiation • positive regulation of transcription by RNA polymerase II • negative regulation of cell population proliferation • negative regulation of transcription, DNA-templated • positive regulation of neuron differentiation • negative regulation of transcription by RNA polymerase II • negative regulation of endothelial cell differentiation • cytokine-mediated signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez Ensembl UniProt RefSeq (mRNA) RefSeq (protein) Location (UCSC) Chr 10: 31.32 – 31.53 Mb Chr 18: 5.59 – 5.78 Mb PubMed search[3] [4] Wikidata
Zinc finger E-box-binding homeobox 1 is a protein that in humans is encoded by the ZEB1 gene .[5] [6] [7]
ZEB1 (previously known as TCF8) encodes a zinc finger and homeodomain transcription factor that represses T-lymphocyte-specific IL2 gene expression by binding to a negative regulatory domain 100 nucleotides 5-prime of the IL2 transcription start site .[7] [6] ZEB1 and its mammalian paralog ZEB2 belongs to the Zeb family within the ZF (zinc finger) class of homeodomain transcription factors. ZEB1 protein has 7 zinc fingers and 1 homeodomain.[8] The structure of the homeodomain is shown on the right.
Clinical significance [ ]
Mutations of the gene are linked to posterior polymorphous corneal dystrophy 3 . ZEB1 downregulates E-cadherin and induces epithelial to mesenchymal transition in breast and other carcinomas.[9] A recent study suggested its contributing role in lung cancer invasiveness and metastasis development.[10] ZEB1 contributes to bone-specific metastasis of breast carcinomas by inactivating BMP signaling through the induction of the expression of BMP-inhibitors.[citation needed ]
References [ ]
^ Jump up to: a b c GRCh38: Ensembl release 89: ENSG00000148516 - Ensembl , May 2017
^ Jump up to: a b c GRCm38: Ensembl release 89: ENSMUSG00000024238 - Ensembl , May 2017
^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ Williams TM, Montoya G, Wu Y, Eddy RL, Byers MG, Shows TB (September 1992). "The TCF8 gene encoding a zinc finger protein (Nil-2-a) resides on human chromosome 10p11.2". Genomics . 14 (1): 194–6. doi :10.1016/S0888-7543(05)80307-6 . PMID 1427828 .
^ Jump up to: a b Williams TM, Moolten D, Burlein J, Romano J, Bhaerman R, Godillot A, Mellon M, Rauscher FJ, Kant JA (December 1991). "Identification of a zinc finger protein that inhibits IL-2 gene expression". Science . 254 (5039): 1791–4. Bibcode :1991Sci...254.1791W . doi :10.1126/science.1840704 . PMID 1840704 .
^ Jump up to: a b "Entrez Gene: ZEB1 zinc finger E-box binding homeobox 1" .
^ Bürglin TR, Affolter M (July 2016). "Homeodomain proteins: an update" . Chromosoma . 125 (3): 497–521. doi :10.1007/s00412-015-0543-8 . PMC 4901127 . PMID 26464018 .
^ Eger A, Aigner K, Sonderegger S, Dampier B, Oehler S, Schreiber M, Berx G, Cano A, Beug H, Foisner R. (March 2005). "DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells" . Oncogene . 31, 24 (14): 2375–85. doi :10.1038/sj.onc.1208429 . PMID 15674322 . CS1 maint: multiple names: authors list (link )
^ Liu W, Huang YJ, Liu C, Yang YY, Liu H, Cui JG, Cheng Y, Gao F, Cai JM, Li BL (April 2014). "Inhibition of TBK1 attenuates radiation-induced epithelial-mesenchymal transition of A549 human lung cancer cells via activation of GSK-3β and repression of ZEB1" . Laboratory Investigation; A Journal of Technical Methods and Pathology . 94 (4): 362–70. doi :10.1038/labinvest.2013.153 . PMID 24468793 .
Further reading [ ]
Franklin AJ, Jetton TL, Shelton KD, Magnuson MA (October 1994). "BZP, a novel serum-responsive zinc finger protein that inhibits gene transcription" . Molecular and Cellular Biology . 14 (10): 6773–88. doi :10.1128/MCB.14.10.6773 . PMC 359208 . PMID 7935395 .
Watanabe Y, Kawakami K, Hirayama Y, Nagano K (December 1993). "Transcription factors positively and negatively regulating the Na,K-ATPase alpha 1 subunit gene". Journal of Biochemistry . 114 (6): 849–55. doi :10.1093/oxfordjournals.jbchem.a124267 . PMID 8138542 .
Ikeda K, Halle JP, Stelzer G, Meisterernst M, Kawakami K (January 1998). "Involvement of negative cofactor NC2 in active repression by zinc finger-homeodomain transcription factor AREB6" . Molecular and Cellular Biology . 18 (1): 10–8. doi :10.1128/mcb.18.1.10 . PMC 121442 . PMID 9418848 .
Turner J, Crossley M (September 1998). "Cloning and characterization of mCtBP2, a co-repressor that associates with basic Krüppel-like factor and other mammalian transcriptional regulators" . The EMBO Journal . 17 (17): 5129–40. doi :10.1093/emboj/17.17.5129 . PMC 1170841 . PMID 9724649 .
Postigo AA, Dean DC (June 1999). "ZEB represses transcription through interaction with the corepressor CtBP" . Proceedings of the National Academy of Sciences of the United States of America . 96 (12): 6683–8. Bibcode :1999PNAS...96.6683P . doi :10.1073/pnas.96.12.6683 . PMC 21975 . PMID 10359772 .
Hlubek F, Löhberg C, Meiler J, Jung A, Kirchner T, Brabletz T (April 2001). "Tip60 is a cell-type-specific transcriptional regulator". Journal of Biochemistry . 129 (4): 635–41. doi :10.1093/oxfordjournals.jbchem.a002901 . PMID 11275565 .
Locklin RM, Riggs BL, Hicok KC, Horton HF, Byrne MC, Khosla S (December 2001). "Assessment of gene regulation by bone morphogenetic protein 2 in human marrow stromal cells using gene array technology" . Journal of Bone and Mineral Research . 16 (12): 2192–204. doi :10.1359/jbmr.2001.16.12.2192 . PMID 11760832 . S2CID 25397480 .
Shaheduzzaman S, Krishnan V, Petrovic A, Bittner M, Meltzer P, Trent J, Venkatesan S, Zeichner S (2002). "Effects of HIV-1 Nef on cellular gene expression profiles". Journal of Biomedical Science . 9 (1): 82–96. doi :10.1007/BF02256581 . PMID 11810028 .
Guaita S, Puig I, Franci C, Garrido M, Dominguez D, Batlle E, Sancho E, Dedhar S, De Herreros AG, Baulida J (October 2002). "Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression" . The Journal of Biological Chemistry . 277 (42): 39209–16. doi :10.1074/jbc.M206400200 . PMID 12161443 .
Costantino ME, Stearman RP, Smith GE, Darling DS (August 2002). "Cell-specific phosphorylation of Zfhep transcription factor" . Biochemical and Biophysical Research Communications . 296 (2): 368–73. doi :10.1016/S0006-291X(02)00880-X . PMC 3682420 . PMID 12163027 .
Postigo AA (May 2003). "Opposing functions of ZEB proteins in the regulation of the TGFbeta/BMP signaling pathway" . The EMBO Journal . 22 (10): 2443–52. doi :10.1093/emboj/cdg225 . PMC 155983 . PMID 12743038 .
Postigo AA, Depp JL, Taylor JJ, Kroll KL (May 2003). "Regulation of Smad signaling through a differential recruitment of coactivators and corepressors by ZEB proteins" . The EMBO Journal . 22 (10): 2453–62. doi :10.1093/emboj/cdg226 . PMC 155984 . PMID 12743039 .
Dillner NB, Sanders MM (January 2004). "Transcriptional activation by the zinc-finger homeodomain protein delta EF1 in estrogen signaling cascades". DNA and Cell Biology . 23 (1): 25–34. doi :10.1089/104454904322745907 . PMID 14965470 .
Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (August 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins" . Proceedings of the National Academy of Sciences of the United States of America . 101 (33): 12130–5. Bibcode :2004PNAS..10112130B . doi :10.1073/pnas.0404720101 . PMC 514446 . PMID 15302935 .
Shimizu S, Krafchak C, Fuse N, Epstein MP, Schteingart MT, Sugar A, Eibschitz-Tsimhoni M, Downs CA, Rozsa F, Trager EH, Reed DM, Boehnke M, Moroi SE, Richards JE (November 2004). "A locus for posterior polymorphous corneal dystrophy (PPCD3) maps to chromosome 10" . American Journal of Medical Genetics. Part A . 130A (4): 372–7. doi :10.1002/ajmg.a.30267 . PMC 1249494 . PMID 15384081 .
Eger A, Aigner K, Sonderegger S, Dampier B, Oehler S, Schreiber M, Berx G, Cano A, Beug H, Foisner R (March 2005). "DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells" . Oncogene . 24 (14): 2375–85. doi :10.1038/sj.onc.1208429 . PMID 15674322 .
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2e19 : Solution structure of the homeobox domain from human NIL-2-A zinc finger protein, transcription factor 8