SNAI1
entrez
6615
canonical
uniprot
O95863
canonical
ensembl
ENSG00000124216
resolver
ensp
ENSP00000244050
resolver
enst
ENST00000244050
resolver
genesymbol
SNAI1
resolver
genesymbol_syn
SNAH
resolver
hgnc
HGNC:11128
resolver
uniprot
B2R842
resolver
uniprot
Q9P113
resolver
uniprot
Q9UBP7
resolver
uniprot
Q9UHH7
resolver
uniprot_entry
SNAI1_HUMAN
resolver
uniprot_sec
B2R842
resolver
uniprot_sec
Q9P113
resolver
uniprot_sec
Q9UBP7
resolver
uniprot_sec
Q9UHH7
resolver
amino_acid_sequence
MPRSFLVRKPSDPNRKPNYSELQDSNPEFTFQQPYDQAHLLAAIPPPEILNPTASLPMLIWDSVLAPQAQPIAWASLRLQESPRVAELTSLSDEDSGKGSQPPSPPSPAPSSFSSTSVSSLEAEAYAAFPGLGQVPKQLAQLSEAKDLQARKAFNCKYCNKEYLSLGALKMHIRSHTLPCVCGTCGKAFSRPWLLQGHVRTHTGEKPFSCPHCSRAFADRSNLRAHLQTHSDVKKYQCQACARTFSRMSLLHKHQESGCSGCPR
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:Q02085, ECO:0000269|PubMed:10655587, ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:16096638, ECO:0000269|PubMed:20121949, ECO:0000269|PubMed:20389281, ECO:0000269|PubMed:20562920, ECO:0000269|PubMed:21300290, ECO:0000269|PubMed:21952048, ECO:0000269|PubMed:23721412, ECO:0000269|PubMed:25827072}.
uniprot
proteins
mass_dalton
29083
uniprot
proteins
mutagenesis
MUTAGEN 2; /note="P->A: Abolishes repressor activity on E-cadherin/CDH1 promoter and binding to KDM1A."; /evidence="ECO:0000269|PubMed:20389281, ECO:0000269|PubMed:20562920"; MUTAGEN 3; /note="R->A: Loss of interaction with KDM1A."; /evidence="ECO:0000269|PubMed:20389281"; MUTAGEN 4; /note="S->A: Loss of interaction with KDM1A."; /evidence="ECO:0000269|PubMed:20389281"; MUTAGEN 5; /note="F->A: Loss of interaction with KDM1A."; /evidence="ECO:0000269|PubMed:20389281"; MUTAGEN 8; /note="R->A: Loss of interaction with KDM1A."; /evidence="ECO:0000269|PubMed:20389281"; MUTAGEN 9; /note="K->A: Loss of interaction with KDM1A."; /evidence="ECO:0000269|PubMed:20389281"; MUTAGEN 9; /note="K->R: Does not affect E-cadherin/CDH1 repression; when associated with R-16."; /evidence="ECO:0000269|PubMed:16096638"; MUTAGEN 11; /note="S->A: Abolishes PKA phosphorylation. Strongly decreases repressor activity on E-cadherin/CDH1 and CLDN1 promoters. Increases protein stability. Affects function in EMT."; /evidence="ECO:0000269|PubMed:19923321"; MUTAGEN 16; /note="K->R: Does not affect E-cadherin repression; when associated with R-9."; /evidence="ECO:0000269|PubMed:16096638"; MUTAGEN 92; /note="S->A: Abolishes CK2 phosphorylation. Strongly decreases repressor activity on E-cadherin/CDH1 and CLDN1 promoters. Increases protein stability. Affects function in cell survival. Abolishes phosphorylation in the serine-rich region; when associated with A-104 and A-107."; /evidence="ECO:0000269|PubMed:19923321"; MUTAGEN 92; /note="S->E: Does not affect repressor activity on E-cadherin/CDH1 promoter."; /evidence="ECO:0000269|PubMed:19923321"; MUTAGEN 96; /note="S->A: Abolishes recognition and ubiquitination by BTRC which increases steady state level and half-life. Preferentially localizes to the nucleus. Induces a more aggressive tissue invasion program. Lower sensitivity to BTRC-triggered degradation, impairs phosphorylation by GSK3B and does not affect NOTCH1-induced degradation; when associated with A-100. Lower sensitivity to BTRC-triggered degradation, impaired phosphorylation by GSK3B and loss of cytoplasmic localization; when associated with A-100; A-107; A-111; A-115 and A-119."; /evidence="ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:20305697, ECO:0000269|PubMed:22128911, ECO:0000269|PubMed:25827072, ECO:0000269|PubMed:29059170"; MUTAGEN 98; /note="K->R: No change. Complete loss of sensitivity to FBXL14- and BTRC-triggered degradation and loss of ability to repress E-cadherin/CDH1; when associated with R-137 and R-146."; /evidence="ECO:0000269|PubMed:16096638, ECO:0000269|PubMed:19955572"; MUTAGEN 100; /note="S->A: Lower sensitivity to BTRC-triggered degradation and impaired phosphorylation by GSK3B; when associated with A-96. Lower sensitivity to BTRC-triggered degradation, impaired phosphorylation by GSK3B and loss of cytoplasmic localization; when associated with A-96; A-107; A-111; A-115 and A-119. Does not affect NOTCH1-induced degradation; when associated with A-96. Abolishes phosphorylation at S-96."; /evidence="ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:20305697, ECO:0000269|PubMed:22128911, ECO:0000269|PubMed:25827072, ECO:0000269|PubMed:29059170"; MUTAGEN 104; /note="S->A: Increases protein stability, does not affect repressor activity on E-cadherin/CDH1 promoter, preferentially localizes to the nucleus, induces a more aggressive tissue invasion program and impairs phosphorylation by GSK3B, binding to BTRC and ubiquitination; when associated with A-107. Impairs phosphorylation in the serine-rich domain/region; when associated with A-92 and A-107. Abolishes phosphorylation at S-96."; /evidence="ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:19923321, ECO:0000269|PubMed:20305697"; MUTAGEN 107; /note="S->A: Lower sensitivity to BTRC-triggered degradation, impaired phosphorylation by GSK3B and loss of cytoplasmic localization; when associated with A-111; A-115 and A-119. Lower sensitivity to BTRC-triggered degradation, impaired phosphorylation by GSK3B and loss of cytoplasmic localization; when associated with A-96; A-100; A-111; A-115 and A-119. Increases protein stability, does not affect repressor activity on E-cadherin promoter, preferentially localizes to the nucleus, induces a more aggressive tissue invasion program and impairs phosphorylation by GSK3B, binding to BTRC and ubiquitination; when associated with A-104. Impairs phosphorylation in the serine-rich region; when associated with A-92 and A-104. Abolishes phosphorylation at S-96."; /evidence="ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:19923321, ECO:0000269|PubMed:20305697, ECO:0000269|PubMed:25827072, ECO:0000269|PubMed:29059170"; MUTAGEN 107; /note="S->E: Predominantly localized to the cytoplasm; when associated with E-111; E-115 and E-119."; /evidence="ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:19923321, ECO:0000269|PubMed:20305697"; MUTAGEN 111; /note="S->A: Lower sensitivity to BTRC-triggered degradation, impaired phosphorylation by GSK3B and loss of cytoplasmic localization; when associated with A-107; A-115 and A-119. Lower sensitivity to BTRC-triggered degradation, impaired phosphorylation by GSK3B and loss of cytoplasmic localization; when associated with A-96; A-100; A-107; A-115 and A-119."; /evidence="ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:25827072, ECO:0000269|PubMed:29059170"; MUTAGEN 111; /note="S->E: Predominantly localized to the cytoplasm; when associated with E-107; E-115 and E-119."; /evidence="ECO:0000269|PubMed:15448698"; MUTAGEN 115; /note="S->A: Lower sensitivity to BTRC-triggered degradation, impaired phosphorylation by GSK3B and loss of cytoplasmic localization; when associated with A-107; A-111 and A-119. Lower sensitivity to BTRC-triggered degradation, impaired phosphorylation by GSK3B and loss of cytoplasmic localization; when associated with A-96; A-100; A-107; A-111 and A-119."; /evidence="ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:25827072, ECO:0000269|PubMed:29059170"; MUTAGEN 115; /note="S->E: Predominantly localized to the cytoplasm; when associated with E-107; E-111 and E-119."; /evidence="ECO:0000269|PubMed:15448698"; MUTAGEN 119; /note="S->A: Lower sensitivity to BTRC-triggered degradation, impaired phosphorylation by GSK3B and loss of cytoplasmic localization; when associated with A-107; A-111 and A-119. Lower sensitivity to BTRC-triggered degradation, impaired phosphorylation by GSK3B and loss of cytoplasmic localization; when associated with A-96; A-100; A-107; A-111 and A-115."; /evidence="ECO:0000269|PubMed:15448698"; MUTAGEN 119; /note="S->E: Predominantly localized to the cytoplasm; when associated with E-107; E-111 and E-115."; /evidence="ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:25827072, ECO:0000269|PubMed:29059170"; MUTAGEN 137; /note="K->R: Lower sensitivity to FBXL14-triggered degradation. Lower sensitivity to FBXL14-triggered degradation; when associated with R-146. Complete loss of sensitivity to FBXL14- and BTRC-triggered degradation and loss of ability to repress E-cadherin; when associated with R-98 and R-146."; /evidence="ECO:0000269|PubMed:16096638, ECO:0000269|PubMed:19955572"; MUTAGEN 146; /note="K->R: Lower sensitivity to FBXL14-triggered degradation. Lower sensitivity to FBXL14-triggered degradation; when associated with R-137. Complete loss of sensitivity to FBXL14- and BTRC-triggered degradation; when associated with R-98 and R-137."; /evidence="ECO:0000269|PubMed:19955572"; MUTAGEN 151..152; /note="RK->EE: Does not affect binding to KPNB1, KPNA2, IPO7 or TNPO1."; /evidence="ECO:0000269|PubMed:19386897"; MUTAGEN 156; /note="C->A: Abolishes binding to KPNB1, KPNA2, IPO7 and TNPO1 and nuclear localization."; /evidence="ECO:0000269|PubMed:19386897"; MUTAGEN 161; /note="K->E: Does not affect binding to KPNB1, KPNA2, IPO7 or TNPO1. No change in subcellular localization. Impairs binding to KPNB1, KPNA2, IPO7 and TNPO1 and abolishes nuclear localization, DNA binding and repressor activity on E-cadherin/CDH1 promoter; when associated with E-170. Abolishes binding to KPNB1, KPNA2, IPO7 and TNPO1 and nuclear localization; when associated with E-187 and/or E-220."; /evidence="ECO:0000269|PubMed:19386897"; MUTAGEN 170; /note="K->E: Does not affect binding to KPNB1, KPNA2, IPO7 or TNPO1. No change in subcellular localization. Impairs binding to KPNB1, KPNA2, IPO7 and TNPO1 and abolishes nuclear localization, DNA binding and repressor activity on E-cadherin/CDH1 promoter; when associated with E-161."; /evidence="ECO:0000269|PubMed:19386897"; MUTAGEN 182; /note="C->A: Impairs binding to KPNB1, IPO7 and TNPO1 and abolishes binding to KPNA2. Localizes to cytoplasm and nucleus."; /evidence="ECO:0000269|PubMed:19386897"; MUTAGEN 187; /note="K->E: Does not affect binding to KPNB1, KPNA2, IPO7 or TNPO1. Impairs binding to KPNB1, KPNA2, IPO7 and TNPO1 and abolishes nuclear localization, DNA binding and repressor activity on E-cadherin/CDH1 promoter; when associated with E-191. Abolishes binding to KPNB1, KPNA2, IPO7 and TNPO1 and nuclear localization; when associated with E-161 and/or E-220."; /evidence="ECO:0000269|PubMed:19386897"; MUTAGEN 191; /note="R->E: Mildly reduces binding to KPNB1 and nuclear import. Does not affect binding to KPNA2, IPO7 or TNPO1. Strongly reduces binding to KPNB1 and nuclear import; when associated with A-193. Loss of binding to KPNB1 and nuclear import; when associated with A-193 and A-196."; /evidence="ECO:0000269|PubMed:19386897, ECO:0000269|PubMed:24699649"; MUTAGEN 193; /note="W->A: Mildly reduces binding to KPNB1 and nuclear import. Strongly reduces binding to KPNB1 and nuclear import; when associated with E-191. Loss of binding to KPNB1 and nuclear import; when associated with E-191 and A-196."; /evidence="ECO:0000269|PubMed:24699649"; MUTAGEN 196; /note="Q->A: Loss of binding to KPNB1 and nuclear import; when associated with E-191 and A-193."; /evidence="ECO:0000269|PubMed:24699649"; MUTAGEN 203; /note="T->A: Abolishes LATS2 phosphorylation. Does not affect binding to LATS2. Reduces protein stability. Equally distributed between nucleus and cytoplasm. Increases capacity to associate with nuclear pore importins. Unable to accumulate in the nucleus. Does not abrogate function."; /evidence="ECO:0000269|PubMed:21952048"; MUTAGEN 203; /note="T->E: Exclusively localizes to the cytoplasm. Reduces capacity to associate with nuclear pore importins. Unable to enter the nucleus. Does not abrogate function."; /evidence="ECO:0000269|PubMed:21952048"; MUTAGEN 210; /note="C->A: Impairs binding to KPNB1, IPO7 and TNPO1 and abolishes binding to KPNA2. Localizes to cytoplasm and nucleus."; /evidence="ECO:0000269|PubMed:19386897"; MUTAGEN 215; /note="R->E: Impairs binding to KPNB1, KPNA2, IPO7 and TNPO1. No change in subcellular localization."; /evidence="ECO:0000269|PubMed:19386897"; MUTAGEN 220; /note="R->E: Does not affect binding to KPNB1, KPNA2, IPO7 or TNPO1. No change in subcellular localization. Impairs binding to KPNB1, KPNA2, IPO7 and TNPO1; when associated with E-222 and E-224. Impairs binding to KPNB1, KPNA2, IPO7 and TNPO1 and abolishes nuclear localization, DNA binding and repressor activity on E-cadherin/CDH1 promoter; when associated with E-224. Abolishes binding to KPNB1, KPNA2, IPO7 and TNPO1 and nuclear localization; when associated with E-161 and/or E-187."; /evidence="ECO:0000269|PubMed:19386897"; MUTAGEN 222; /note="N->E: Does not affect binding to KPNB1, KPNA2, IPO7 or TNPO1. No change in subcellular localization. Impairs binding to KPNB1, KPNA2, IPO7 and TNPO1; when associated with E-220 and E-224."; /evidence="ECO:0000269|PubMed:19386897"; MUTAGEN 224; /note="R->E: Does not affect binding to KPNB1, KPNA2, IPO7 or TNPO1. No change in subcellular localization. Impairs binding to KPNB1, KPNA2, IPO7 and TNPO1; when associated with E-220 and E-222. Impairs binding to KPNB1, KPNA2, IPO7 and TNPO1 and abolishes nuclear localization, DNA binding and repressor activity on E-cadherin/CDH1 promoter; when associated with E-220. Strongly reduces binding to KPNB1 and nuclear import; when associated with A-228."; /evidence="ECO:0000269|PubMed:19386897, ECO:0000269|PubMed:24699649"; MUTAGEN 228; /note="Q->A: Very minor effect on binding to KPNB1 and nuclear import. Strongly reduces binding to KPNB1 and nuclear import; when associated with E-224."; /evidence="ECO:0000269|PubMed:24699649"; MUTAGEN 232..235; /note="DVKK->KVEE: Does not affect binding to KPNB1, KPNA2, IPO7 or TNPO1."; /evidence="ECO:0000269|PubMed:19386897"; MUTAGEN 238; /note="C->A: Impairs binding to KPNB1 and IPO7 and abolishes binding to KPNA2 and TNPO1 and nuclear localization."; /evidence="ECO:0000269|PubMed:19386897"; MUTAGEN 239; /note="Q->E: Does not affect binding to KPNB1, KPNA2, IPO7, TNPO1 or DNA."; /evidence="ECO:0000269|PubMed:19386897"; MUTAGEN 246; /note="S->A: Decreases repression activity on E-cadherin/CDH1, occludin and aromatase promoters. Preferentially localizes to the cytoplasm. Abolishes phosphorylation by PAK1."; /evidence="ECO:0000269|PubMed:15833848"; MUTAGEN 247; /note="R->E: Mildly reduces binding to KPNB1 and nuclear import."; /evidence="ECO:0000269|PubMed:24699649
uniprot
proteins
post_translational_modification
PTM: 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). {ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:15833848, ECO:0000269|PubMed:19923321, ECO:0000269|PubMed:20305697, ECO:0000269|PubMed:21952048, ECO:0000269|PubMed:24157836, ECO:0000269|PubMed:25827072, ECO:0000269|PubMed:29059170}.; PTM: 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). {ECO:0000269|PubMed:19955572, ECO:0000269|PubMed:20385133, ECO:0000269|PubMed:24157836, ECO:0000269|PubMed:25827072, ECO:0000269|PubMed:29059170, ECO:0000269|PubMed:31911859}.; PTM: O-GlcNAcylation at Ser-112 is enhanced in hyperglycaemic conditions, it opposes phosphorylation by GSK3B, and stabilizes the protein.; PTM: ADP-ribosylation by PARP1 increases protein half-life and may be involved in TGFB-induced SNAI1 up-regulation.
uniprot
proteins
protein_family
Snail C2H2-type zinc-finger protein family
uniprot
proteins
pubmed
10543399
uniprot
proteins
pubmed
10585766
uniprot
proteins
pubmed
10655587
uniprot
proteins
pubmed
11245431
uniprot
proteins
pubmed
11780052
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15448698
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15647282
uniprot
proteins
pubmed
15833848
uniprot
proteins
pubmed
15836774
uniprot
proteins
pubmed
16096638
uniprot
proteins
pubmed
18331720
uniprot
proteins
pubmed
19386897
uniprot
proteins
pubmed
19923321
uniprot
proteins
pubmed
19955572
uniprot
proteins
pubmed
20121949
uniprot
proteins
pubmed
20305697
uniprot
proteins
pubmed
20385133
uniprot
proteins
pubmed
20389281
uniprot
proteins
pubmed
20562920
uniprot
proteins
pubmed
20959806
uniprot
proteins
pubmed
21300290
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21454664
uniprot
proteins
pubmed
21577210
uniprot
proteins
pubmed
21952048
uniprot
proteins
pubmed
22128911
uniprot
proteins
pubmed
23721412
uniprot
proteins
pubmed
24157836
uniprot
proteins
pubmed
24699649
uniprot
proteins
pubmed
25827072
uniprot
proteins
pubmed
25893292
uniprot
proteins
pubmed
29059170
uniprot
proteins
pubmed
31911859
uniprot
proteins
sequence_length
264
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15833848, ECO:0000269|PubMed:20389281, ECO:0000269|PubMed:24157836, ECO:0000269|PubMed:24699649, ECO:0000269|PubMed:25827072, ECO:0000269|PubMed:25893292}. Cytoplasm {ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15833848}. Note=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. {ECO:0000269|PubMed:15448698}.
uniprot
proteins