ZEB1

ZEB1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2E19
Identifiers
Aliases	ZEB1 , zinc finger E-box binding homeobox 1, AREB6, BZP, DELTAEF1, FECD6, NIL2A, PPCD3, TCF8, ZFHEP, ZFHX1A
External IDs	OMIM: 189909 MGI: 1344313 HomoloGene: 31779 GeneCards: ZEB1
Gene location (Human) Chr. Chromosome 10 (human) [1] Band 10p11.22 Start 31,318,495 bp [1] End 31,529,814 bp [1]
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]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Achilles tendon optic nerve endothelial cell biceps brachii stromal cell of endometrium triceps brachii muscle ganglionic eminence right ventricle pericardium synovial joint Top expressed in internal carotid artery substantia nigra motor neuron external carotid artery semi-lunar valve carotid body ascending aorta suprachiasmatic nucleus ankle median eminence More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding transcription corepressor activity transcription coactivator activity zinc ion binding transcription factor binding chromatin binding metal ion binding protein binding nucleic acid binding DNA-binding transcription repressor activity, RNA polymerase II-specific DNA-binding transcription factor activity E-box binding 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 6935 21417 Ensembl ENSG00000148516 ENSMUSG00000024238 UniProt P37275 Q64318 RefSeq (mRNA) NM_001128128 NM_001174093 NM_001174094 NM_001174095 NM_001174096 NM_030751 NM_001323638 NM_001323641 NM_001323642 NM_001323643 NM_001323644 NM_001323645 NM_001323646 NM_001323647 NM_001323648 NM_001323649 NM_001323650 NM_001323651 NM_001323652 NM_001323653 NM_001323654 NM_001323655 NM_001323656 NM_001323657 NM_001323658 NM_001323659 NM_001323660 NM_001323661 NM_001323662 NM_001323663 NM_001323664 NM_001323665 NM_001323666 NM_001323671 NM_001323672 NM_001323673 NM_001323674 NM_001323675 NM_001323676 NM_001323677 NM_001323678 NM_011546 NM_001360981 NM_001360982 RefSeq (protein) NP_001121600 NP_001167564 NP_001167565 NP_001167566 NP_001167567 NP_001310567 NP_001310570 NP_001310571 NP_001310572 NP_001310573 NP_001310574 NP_001310575 NP_001310576 NP_001310577 NP_001310578 NP_001310579 NP_001310580 NP_001310581 NP_001310582 NP_001310583 NP_001310584 NP_001310585 NP_001310586 NP_001310587 NP_001310588 NP_001310589 NP_001310590 NP_001310591 NP_001310592 NP_001310593 NP_001310594 NP_001310595 NP_001310600 NP_001310601 NP_001310602 NP_001310603 NP_001310604 NP_001310605 NP_001310606 NP_001310607 NP_110378 NP_035676 NP_001347910 NP_001347911 Location (UCSC) Chr 10: 31.32 – 31.53 Mb Chr 18: 5.59 – 5.78 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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 seven zinc fingers and one 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] Overexpression of ZEB1 has been identified as a potential risk factor for recurrence and poor prognosis in several types of cancers. ^[11]

References

1. GRCh38: Ensembl release 89: ENSG00000148516 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000024238 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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.
7. "Entrez Gene: ZEB1 zinc finger E-box binding homeobox 1".
8. 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.
9. 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.
10. 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.
11. Lu J, Fei F, Wu C, Mei J, Xu J, Lu P (September 2022). "ZEB1: Catalyst of immune escape during tumor metastasis". Biomed Pharmacother. 153: 113490. doi: 10.1016/j.biopha.2022.113490 . PMID   36076506.

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.

External links

• FactorBook ZEB1