ZEB1

Protein-coding gene in the species Homo sapiens
ZEB1
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

2E19

Identifiers
AliasesZEB1, zinc finger E-box binding homeobox 1, AREB6, BZP, DELTAEF1, FECD6, NIL2A, PPCD3, TCF8, ZFHEP, ZFHX1A
External IDsOMIM: 189909 MGI: 1344313 HomoloGene: 31779 GeneCards: ZEB1
Gene location (Human)
Chromosome 10 (human)
Chr.Chromosome 10 (human)[1]
Chromosome 10 (human)
Genomic location for ZEB1
Genomic location for ZEB1
Band10p11.22Start31,318,495 bp[1]
End31,529,814 bp[1]
Gene location (Mouse)
Chromosome 18 (mouse)
Chr.Chromosome 18 (mouse)[2]
Chromosome 18 (mouse)
Genomic location for ZEB1
Genomic location for ZEB1
Band18 4.42 cM|18 A1Start5,591,860 bp[2]
End5,775,467 bp[2]
RNA expression pattern
Bgee
HumanMouse (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
SpeciesHumanMouse
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 MbChr 18: 5.59 – 5.78 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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 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] Overexpression of ZEB1 has been identified as a potential risk factor for recurrence and poor prognosis in several types of cancers.[11]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000148516 - Ensembl, May 2017
  2. ^ a b c 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. ^ 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.
  7. ^ a b "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

  • v
  • t
  • e
  • 2e19: Solution structure of the homeobox domain from human NIL-2-A zinc finger protein, transcription factor 8
    2e19: Solution structure of the homeobox domain from human NIL-2-A zinc finger protein, transcription factor 8
  • v
  • t
  • e
(1) Basic domains
(1.1) Basic leucine zipper (bZIP)
(1.2) Basic helix-loop-helix (bHLH)
Group A
Group B
Group C
bHLH-PAS
Group D
Group E
Group F
bHLH-COE
(1.3) bHLH-ZIP
(1.4) NF-1
(1.5) RF-X
(1.6) Basic helix-span-helix (bHSH)
(2) Zinc finger DNA-binding domains
(2.1) Nuclear receptor (Cys4)
subfamily 1
subfamily 2
subfamily 3
subfamily 4
subfamily 5
subfamily 6
subfamily 0
(2.2) Other Cys4
(2.3) Cys2His2
(2.4) Cys6
(2.5) Alternating composition
(2.6) WRKY
(3) Helix-turn-helix domains
(3.1) Homeodomain
Antennapedia
ANTP class
protoHOX
Hox-like
metaHOX
NK-like
other
(3.2) Paired box
(3.3) Fork head / winged helix
(3.4) Heat shock factors
(3.5) Tryptophan clusters
(3.6) TEA domain
  • transcriptional enhancer factor
(4) β-Scaffold factors with minor groove contacts
(4.1) Rel homology region
(4.2) STAT
(4.3) p53-like
(4.4) MADS box
(4.6) TATA-binding proteins
(4.7) High-mobility group
(4.9) Grainyhead
(4.10) Cold-shock domain
(4.11) Runt
(0) Other transcription factors
(0.2) HMGI(Y)
(0.3) Pocket domain
(0.5) AP-2/EREBP-related factors
(0.6) Miscellaneous
see also transcription factor/coregulator deficiencies


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