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Showing Protein Zinc finger protein SNAI1 (HMDBP14022)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 0 metabolites
Identification
HMDB Protein ID HMDBP14022
Secondary Accession Numbers None
Name Zinc finger protein SNAI1
Synonyms
  1. Protein snail homolog 1
  2. Protein sna
Gene Name SNAI1
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Involved in induction of the epithelial to mesenchymal transition (EMT), formation and maintenance of embryonic mesoderm, growth arrest, survival and cell migration. Binds to 3 E-boxes of the E-cadherin/CDH1 gene promoter and to the promoters of CLDN7 and KRT8 and, in association with histone demethylase KDM1A which it recruits to the promoters, causes a decrease in dimethylated H3K4 levels and represses transcription (PubMed:20389281, PubMed:20562920). The N-terminal SNAG domain competes with histone H3 for the same binding site on the histone demethylase complex formed by KDM1A and RCOR1, and thereby inhibits demethylation of histone H3 at 'Lys-4' (in vitro) (PubMed:20389281, PubMed:21300290, PubMed:23721412). During EMT, involved with LOXL2 in negatively regulating pericentromeric heterochromatin transcription (By similarity). SNAI1 recruits LOXL2 to pericentromeric regions to oxidize histone H3 and repress transcription which leads to release of heterochromatin component CBX5/HP1A, enabling chromatin reorganization and acquisition of mesenchymal traits (By similarity). Associates with EGR1 and SP1 to mediate tetradecanoyl phorbol acetate (TPA)-induced up-regulation of CDKN2B, possibly by binding to the CDKN2B promoter region 5'-TCACA-3. In addition, may also activate the CDKN2B promoter by itself.
Pathways
  • Adherens junction
Reactions Not Available
GO Classification
Biological Process
positive regulation of cell migration
cell migration
palate development
heterochromatin organization
positive regulation of epithelial to mesenchymal transition
epithelial to mesenchymal transition
aortic valve morphogenesis
cartilage morphogenesis
epithelial to mesenchymal transition involved in endocardial cushion formation
negative regulation of cell differentiation involved in embryonic placenta development
negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage
negative regulation of vitamin D biosynthetic process
Notch signaling involved in heart development
regulation of bicellular tight junction assembly
trophoblast giant cell differentiation
osteoblast differentiation
regulation of transcription from RNA polymerase II promoter
left/right pattern formation
positive regulation of transcription, DNA-dependent
negative regulation of transcription from RNA polymerase II promoter
mesoderm formation
hair follicle morphogenesis
negative regulation of DNA damage response, signal transduction by p53 class mediator
Cellular Component
cytosol
cytoplasm
nucleus
centromeric heterochromatin
nucleoplasm
fibrillar center
intracellular membrane-bounded organelle
Molecular Function
metal ion binding
DNA-binding transcription repressor activity, RNA polymerase II-specific
RNA polymerase II transcription regulatory region sequence-specific DNA binding
sequence-specific DNA binding transcription factor activity
kinase binding
E-box binding
RNA polymerase II core promoter proximal region sequence-specific DNA binding
sequence-specific double-stranded DNA binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 264
Molecular Weight 29082.725
Theoretical pI 8.644
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID O95863
UniProtKB/Swiss-Prot Entry Name SNAI1_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  4. Zhou BP, Deng J, Xia W, Xu J, Li YM, Gunduz M, Hung MC: Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition. Nat Cell Biol. 2004 Oct;6(10):931-40. Epub 2004 Sep 26. [PubMed:15448698 ]
  5. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [PubMed:21406692 ]
  6. Okubo T, Truong TK, Yu B, Itoh T, Zhao J, Grube B, Zhou D, Chen S: Down-regulation of promoter 1.3 activity of the human aromatase gene in breast tissue by zinc-finger protein, snail (SnaH). Cancer Res. 2001 Feb 15;61(4):1338-46. [PubMed:11245431 ]
  7. Twigg SR, Wilkie AO: Characterisation of the human snail (SNAI1) gene and exclusion as a major disease gene in craniosynostosis. Hum Genet. 1999 Oct;105(4):320-6. doi: 10.1007/s004399900143. [PubMed:10543399 ]
  8. Paznekas WA, Okajima K, Schertzer M, Wood S, Jabs EW: Genomic organization, expression, and chromosome location of the human SNAIL gene (SNAI1) and a related processed pseudogene (SNAI1P). Genomics. 1999 Nov 15;62(1):42-9. doi: 10.1006/geno.1999.6010. [PubMed:10585766 ]
  9. Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J, Garcia De Herreros A: The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol. 2000 Feb;2(2):84-9. doi: 10.1038/35000034. [PubMed:10655587 ]
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  11. Peinado H, Del Carmen Iglesias-de la Cruz M, Olmeda D, Csiszar K, Fong KS, Vega S, Nieto MA, Cano A, Portillo F: A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor progression. EMBO J. 2005 Oct 5;24(19):3446-58. doi: 10.1038/sj.emboj.7600781. Epub 2005 Aug 18. [PubMed:16096638 ]
  12. Yamasaki H, Sekimoto T, Ohkubo T, Douchi T, Nagata Y, Ozawa M, Yoneda Y: Zinc finger domain of Snail functions as a nuclear localization signal for importin beta-mediated nuclear import pathway. Genes Cells. 2005 May;10(5):455-64. doi: 10.1111/j.1365-2443.2005.00850.x. [PubMed:15836774 ]
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  15. Lin Y, Wu Y, Li J, Dong C, Ye X, Chi YI, Evers BM, Zhou BP: The SNAG domain of Snail1 functions as a molecular hook for recruiting lysine-specific demethylase 1. EMBO J. 2010 Jun 2;29(11):1803-16. doi: 10.1038/emboj.2010.63. Epub 2010 Apr 13. [PubMed:20389281 ]
  16. Park SY, Kim HS, Kim NH, Ji S, Cha SY, Kang JG, Ota I, Shimada K, Konishi N, Nam HW, Hong SW, Yang WH, Roth J, Yook JI, Cho JW: Snail1 is stabilized by O-GlcNAc modification in hyperglycaemic condition. EMBO J. 2010 Nov 17;29(22):3787-96. doi: 10.1038/emboj.2010.254. Epub 2010 Oct 19. [PubMed:20959806 ]
  17. Hu CT, Chang TY, Cheng CC, Liu CS, Wu JR, Li MC, Wu WS: Snail associates with EGR-1 and SP-1 to upregulate transcriptional activation of p15INK4b. FEBS J. 2010 Mar;277(5):1202-18. doi: 10.1111/j.1742-4658.2009.07553.x. Epub 2010 Feb 1. [PubMed:20121949 ]
  18. Lim SO, Kim H, Jung G: p53 inhibits tumor cell invasion via the degradation of snail protein in hepatocellular carcinoma. FEBS Lett. 2010 Jun 3;584(11):2231-6. doi: 10.1016/j.febslet.2010.04.006. Epub 2010 Apr 10. [PubMed:20385133 ]
  19. Vinas-Castells R, Beltran M, Valls G, Gomez I, Garcia JM, Montserrat-Sentis B, Baulida J, Bonilla F, de Herreros AG, Diaz VM: The hypoxia-controlled FBXL14 ubiquitin ligase targets SNAIL1 for proteasome degradation. J Biol Chem. 2010 Feb 5;285(6):3794-3805. doi: 10.1074/jbc.M109.065995. Epub 2009 Dec 2. [PubMed:19955572 ]
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  21. Xu Y, Lee SH, Kim HS, Kim NH, Piao S, Park SH, Jung YS, Yook JI, Park BJ, Ha NC: Role of CK1 in GSK3beta-mediated phosphorylation and degradation of snail. Oncogene. 2010 May 27;29(21):3124-33. doi: 10.1038/onc.2010.77. Epub 2010 Mar 22. [PubMed:20305697 ]
  22. Lim SO, Kim HS, Quan X, Ahn SM, Kim H, Hsieh D, Seong JK, Jung G: Notch1 binds and induces degradation of Snail in hepatocellular carcinoma. BMC Biol. 2011 Nov 30;9:83. doi: 10.1186/1741-7007-9-83. [PubMed:22128911 ]
  23. Sekimoto T, Miyamoto Y, Arai S, Yoneda Y: Importin alpha protein acts as a negative regulator for Snail protein nuclear import. J Biol Chem. 2011 Apr 29;286(17):15126-31. doi: 10.1074/jbc.M110.213579. Epub 2011 Mar 17. [PubMed:21454664 ]
  24. Rodriguez MI, Gonzalez-Flores A, Dantzer F, Collard J, de Herreros AG, Oliver FJ: Poly(ADP-ribose)-dependent regulation of Snail1 protein stability. Oncogene. 2011 Oct 20;30(42):4365-72. doi: 10.1038/onc.2011.153. Epub 2011 May 16. [PubMed:21577210 ]
  25. Zhang K, Rodriguez-Aznar E, Yabuta N, Owen RJ, Mingot JM, Nojima H, Nieto MA, Longmore GD: Lats2 kinase potentiates Snail1 activity by promoting nuclear retention upon phosphorylation. EMBO J. 2012 Jan 4;31(1):29-43. doi: 10.1038/emboj.2011.357. Epub 2011 Sep 27. [PubMed:21952048 ]
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  27. Choi S, Yamashita E, Yasuhara N, Song J, Son SY, Won YH, Hong HR, Shin YS, Sekimoto T, Park IY, Yoneda Y, Lee SJ: Structural basis for the selective nuclear import of the C2H2 zinc-finger protein Snail by importin beta. Acta Crystallogr D Biol Crystallogr. 2014 Apr;70(Pt 4):1050-60. doi: 10.1107/S1399004714000972. Epub 2014 Mar 19. [PubMed:24699649 ]
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