Recombinant Human SNAIL protein (denatured)

Specifications

Form

Liquid

General info

Function

Involved in induction of the epithelial to mesenchymal transition (EMT), formation and maintenance of embryonic mesoderm, growth arrest, survival and cell migration (PubMed : 10655587, PubMed : 15647282, PubMed : 20389281, PubMed : 20562920, PubMed : 21952048, PubMed : 25827072). 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 : 10655587, 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 (PubMed : 16096638). 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 (PubMed : 20121949). In addition, may also activate the CDKN2B promoter by itself (PubMed : 20121949).

Sequence similarities

Belongs to the snail C2H2-type zinc-finger protein family.

Post-translational modifications

Phosphorylated by GSK3B (PubMed:15448698, PubMed:15647282, PubMed:20305697, PubMed:25827072, PubMed:29059170). Once phosphorylated, it becomes a target for ubiquitination by BTRC, the ECS(SPSB3) or the SCF(FBXO11) complexes (PubMed:15647282, PubMed:29059170). Phosphorylation by CSNK1E, probably at Ser-104, provides the priming site for the subsequent phosphorylation by GSK3B, probably at Ser-100 and Ser-96 (PubMed:19923321, PubMed:20305697). Phosphorylation by PAK1 may modulate its transcriptional activity by promoting increased accumulation in the nucleus (PubMed:15833848). Phosphorylation at Ser-11 and Ser-92 positively regulates its functions in induction of EMT and cell survival, respectively (PubMed:19923321). 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 (PubMed:21952048, PubMed:24157836).. Ubiquitinated on Lys-98, Lys-137 and Lys-146 by FBXL14 and BTRC leading to degradation (PubMed:19955572). BTRC-triggered ubiquitination requires previous GSK3B-mediated SNAI1 phosphorylation (PubMed:19955572). Ubiquitinated by the SCF(FBXO11) complex; ubiquitination requires previous GSK3B-mediated SNAI1 phosphorylation (PubMed:25827072). Ubiquitinated by the ECS(SPSB3) complex; ubiquitination requires previous GSK3B-mediated SNAI1 phosphorylation (PubMed:29059170). Ubiquitination induced upon interaction with NOTCH1 or TP53/p53 is mediated by MDM2 (PubMed:20385133). Ubiquitinated in a FBXL5-dependent manner; preventing interaction with DNA and promoting its degradation (PubMed:24157836). Deubiquitinated by USP37; leading to stabilization (PubMed:31911859).. 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.

Subcellular localisation

Nucleus