SNAI1

The Drosophila embryonic protein snail is a zinc finger transcriptional repressor which downregulates the expression of ectodermal genes within the mesoderm. The nuclear protein encoded by this gene is structurally similar to the Drosophila snail protein, and is also thought to be critical for mesoderm formation in the developing embryo. At least two variants of a similar processed pseudogene have been found on chromosome 2. [provided by RefSeq, Jul 2008]

Snail Family Transcriptional Repressor 1

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.

Biological Process aortic valve morphogenesisManual Assertion Based On ExperimentTAS:BHF-UCL
Biological Process cartilage morphogenesisIEA:Ensembl
Biological Process epithelial cell migrationIEA:Ensembl
Biological Process epithelial to mesenchymal transitionManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process epithelial to mesenchymal transition involved in endocardial cushion formationISS:BHF-UCL
Biological Process hair follicle morphogenesisIEA:Ensembl
Biological Process heterochromatin organizationISS:UniProtKB
Biological Process left/right pattern formationIEA:Ensembl
Biological Process mesoderm formationISS:UniProtKB
Biological Process negative regulation of cell differentiation involved in embryonic placenta developmentIEA:Ensembl
Biological Process negative regulation of DNA damage response, signal transduction by p53 class mediatorManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process negative regulation of intrinsic apoptotic signaling pathway in response to DNA damageManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of vitamin D biosynthetic processManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process Notch signaling involved in heart developmentISS:BHF-UCL
Biological Process osteoblast differentiationManual Assertion Based On ExperimentIEP:UniProtKB
Biological Process positive regulation of cell migrationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of DNA-templated transcriptionManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of epithelial to mesenchymal transitionManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process regulation of bicellular tight junction assemblyManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central
Biological Process roof of mouth developmentIEA:Ensembl
Biological Process trophoblast giant cell differentiationIEA:Ensembl

Nucleus
Cytoplasm
Once phosphorylated (probably on Ser-107, Ser-111, Ser-115 and Ser-119) it is exported from the nucleus to the cytoplasm where subsequent phosphorylation of the destruction motif and ubiquitination involving BTRC occurs.

Phosphorylated by GSK3B. Once phosphorylated, it becomes a target for BTRC ubiquitination. Phosphorylation by CSNK1E, probably at Ser-104, provides the priming site for the subsequent phosphorylation by GSK3B, probably at Ser-100 and Ser-96. Phosphorylation by PAK1 may modulate its transcriptional activity by promoting increased accumulation in the nucleus. Phosphorylation at Ser-11 and Ser-92 positively regulates its functions in induction of EMT and cell survival, respectively. Phosphorylation by LATS2, upon mitotic stress, oncogenic stress or Hippo pathway activation, occurs in the nucleus and promotes nuclear retention and stabilization of total cellular protein level.
Ubiquitinated on Lys-98, Lys-137 and Lys-146 by FBXL14 and BTRC leading to degradation. BTRC-triggered ubiquitination requires previous GSK3B-mediated SNAI1 phosphorylation. Ubiquitination induced upon interaction with NOTCH1 or TP53/p53 is mediated by MDM2.
O-GlcNAcylation at Ser-112 is enhanced in hyperglycaemic conditions, it opposes phosphorylation by GSK3B, and stabilizes the protein.
ADP-ribosylation by PARP1 increases protein half-life and may be involved in TGFB-induced SNAI1 up-regulation.