O95863 (SNAI1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Zinc finger protein SNAI1

Alternative name(s):
Protein snail homolog 1
Short name=Protein sna

Gene names

Name:	SNAI1
Synonyms:	SNAH

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	264 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. 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. Ref.7 Ref.10 Ref.12 Ref.16 Ref.21 Ref.26
Subunit structure	Interacts with FBXL14 and GSK3B. Interacts with BTRC; interaction occurs when it is phosphorylated on the destruction motif. Interacts (via SNAG domain) with WTIP (via LIM domains) By similarity. Interacts (via SNAG domain) with LIMD1 (via LIM domains), and AJUBA (via LIM domains). Interacts with LOXL2 and LOXL3. Interacts (via N-terminal region) with CSNK2A1. Interacts with EGR1 upon TPA induction. Interacts (via N-terminal region) with LATS2; the interaction is dependent on LATS2 kinase activity but independent of SNAI1 Thr-203 phosphorylation. Interacts (via zinc fingers) with KPNB1 and TNPO1; the interactions mediate nuclear import. Interacts (via zinc fingers) with KPNA1; the interaction disrupts the transport complex with KPNB1 and prevents nuclear import increasing SNAI1 degradation in the cytoplasm. Interacts (via zinc fingers) with KPNA2; the interaction, in combination with KPNB1, mediates nuclear import. Interacts with KPNA4; this interaction mediates nuclear import. May interact (via zinc fingers) with IPO7. Interacts (via zinc fingers) with PARP1; the interaction requires SNAI1 to be poly-ADP-ribosylated and non-phosphorylated (active) by GSK3B. Interacts (via SNAG domain) with KDM1A; the interaction is necessary for the down-regulation of dimethylated H3K4 mark and promoter activity of E-cadherin/CDH1, CDN7 and KRT8. Interacts with TP53/p53 and (via zinc fingers) with NOTCH1 (via intracellular domain); the interactions induce SNAI1 degradation via MDM2-mediated ubiquitination and inhibit SNAI1-induced cell invasion. Interacts with MDM2; the interaction promotes SNAI1 ubiquitination. Interacts (via zinc fingers) with CSNK1E. Interacts with PAK1. Ref.8 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.25
Subcellular location	Nucleus. Cytoplasm. 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. Ref.8 Ref.9 Ref.11 Ref.18 Ref.22 Ref.25 Ref.26
Tissue specificity	Expressed in a variety of tissues with the highest expression in kidney. Expressed in mesenchymal and epithelial cell lines. Ref.7
Induction	Induced by TPA maximally by 2.5-fold at 4 hours, in HepG2 cells (at protein level). Ref.16
Post-translational modification	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. Ref.8 Ref.9 Ref.12 Ref.19 Ref.20 Ref.26 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. Ref.8 Ref.17 Ref.18 Ref.22 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.
Sequence similarities	Belongs to the snail C2H2-type zinc-finger protein family. Contains 4 C2H2-type zinc fingers.
Caution	The interaction with mouse KPNA2 may prevent SNAI1 nuclear import (Ref.23).

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Developmental protein
PTM	ADP-ribosylation Glycoprotein Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Notch signaling involved in heart development Inferred from sequence or structural similarity. Source: BHF-UCL cartilage morphogenesis Inferred from electronic annotation. Source: Compara cell migration Inferred from electronic annotation. Source: Compara epithelial to mesenchymal transition Inferred from direct assay Ref.10. Source: UniProtKB hair follicle morphogenesis Inferred from electronic annotation. Source: Compara left/right pattern formation Inferred from electronic annotation. Source: Compara mesoderm formation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of DNA damage response, signal transduction by p53 class mediator Inferred from mutant phenotype PubMed 15314165. Source: BHF-UCL negative regulation of apoptotic process Inferred from mutant phenotype PubMed 15314165. Source: BHF-UCL negative regulation of cell differentiation involved in embryonic placenta development Inferred from electronic annotation. Source: Compara negative regulation of vitamin D biosynthetic process Inferred from direct assay PubMed 19502595. Source: BHF-UCL osteoblast differentiation Inferred from expression pattern PubMed 20128911. Source: UniProtKB palate development Inferred from electronic annotation. Source: Compara positive regulation of cell migration Inferred from mutant phenotype PubMed 20018240. Source: UniProtKB positive regulation of epithelial to mesenchymal transition Inferred from mutant phenotype PubMed 20018240. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from mutant phenotype PubMed 20018240. Source: UniProtKB regulation of tight junction assembly Inferred from mutant phenotype PubMed 15314165. Source: BHF-UCL trophoblast giant cell differentiation Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from direct assay Ref.8Ref.18. Source: UniProtKB nucleus Inferred from direct assay Ref.8Ref.18. Source: UniProtKB
Molecular_function	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Inferred from direct assay PubMed 11912130. Source: BHF-UCL sequence-specific DNA binding Inferred from electronic annotation. Source: Compara zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GSK3B	P49841	4	EBI-1045459,EBI-373586
KDM1A	O60341	4	EBI-1045459,EBI-710124
PARP1	P09874	10	EBI-1045459,EBI-355676

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 264

264

Zinc finger protein SNAI1

PRO_0000047029

Regions

Zinc finger

154 – 176

23

C2H2-type 1

Zinc finger

178 – 202

25

C2H2-type 2

Zinc finger

208 – 230

23

C2H2-type 3

Zinc finger

236 – 259

24

C2H2-type 4; atypical

Region

1 – 20

20

SNAG domain By similarity

Region

10 – 40

31

LATS2 binding

Region

120 – 151

32

Required for FBXL14-triggered degradation

Region

151 – 264

114

Required for nuclear localization and interaction with KPNB1, NOTCH1 and PARP1

Motif

95 – 100

6

Destruction motif

Compositional bias

90 – 120

31

Ser-rich

Amino acid modifications

Modified residue

11

1

Phosphoserine; by PKA Ref.19

Modified residue

82

1

Phosphoserine Ref.19

Modified residue

92

1

Phosphoserine; by CK2 Ref.19

Modified residue

96

1

Phosphoserine Ref.20

Modified residue

100

1

Phosphoserine Probable

Modified residue

104

1

Phosphoserine Ref.12 Ref.19

Modified residue

107

1

Phosphoserine Ref.12 Ref.19

Modified residue

111

1

Phosphoserine Probable

Modified residue

115

1

Phosphoserine Probable

Modified residue

119

1

Phosphoserine Probable

Modified residue

203

1

Phosphothreonine; by LATS2 Ref.26

Modified residue

246

1

Phosphoserine; by PAK1 Ref.9

Glycosylation

112

1

O-linked (GlcNAc...) Ref.15

Cross-link

98

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)

Cross-link

137

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)

Cross-link

146

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)

Natural variations

Natural variant

66

1

A → V.
Corresponds to variant rs34261470 [ dbSNP | Ensembl ].

VAR_069162

Natural variant

118

1

V → A. Ref.1
Corresponds to variant rs4647958 [ dbSNP | Ensembl ].

VAR_019969

Experimental info

Mutagenesis

2

1

P → A: Abolishes repressor activity on E-cadherin/CDH1 promoter and binding to KDM1A. Ref.21

Mutagenesis

9

1

K → R: Does not affect E-cadherin/CDH1 repression; when associated with R-16. Ref.10

Mutagenesis

11

1

S → A: Abolishes PKA phosphorylation. Strongly decreases repressor activity on E-cadherin/CDH1 and CLDN1 promoters. Increases protein stability. Affects function in EMT. Ref.19

Mutagenesis

16

1

K → R: Does not affect E-cadherin repression; when associated with R-9. Ref.10

Mutagenesis

92

1

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. Ref.19

Mutagenesis

92

1

S → E: Does not affect repressor activity on E-cadherin/CDH1 promoter. Ref.19

Mutagenesis

96

1

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. Ref.8 Ref.12 Ref.20 Ref.22

Mutagenesis

98

1

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. Ref.10 Ref.18

Mutagenesis

100

1

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. Ref.8 Ref.20 Ref.22

Mutagenesis

104

1

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. Ref.12 Ref.19 Ref.20

Mutagenesis

107

1

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. Ref.8 Ref.12 Ref.19 Ref.20

Mutagenesis

107

1

S → E: Predominantly localized to the cytoplasm; when associated with E-111; E-115 and E-119. Ref.8 Ref.12 Ref.19 Ref.20

Mutagenesis

111

1

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. Ref.8

Mutagenesis

111

1

S → E: Predominantly localized to the cytoplasm; when associated with E-107; E-115 and E-119. Ref.8

Mutagenesis

115

1

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. Ref.8

Mutagenesis

115

1

S → E: Predominantly localized to the cytoplasm; when associated with E-107; E-111 and E-119. Ref.8

Mutagenesis

119

1

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. Ref.8

Mutagenesis

119

1

S → E: Predominantly localized to the cytoplasm; when associated with E-107; E-111 and E-115. Ref.8

Mutagenesis

137

1

K → R: Lower sensitivity to FBXL14-triggered degradation. Lower sensitivity to FBXL14-triggered degradation; when associated to 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. Ref.10 Ref.18

Mutagenesis

146

1

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. Ref.18

Mutagenesis

151 – 152

2

RK → EE: Does not affect binding to KPNB1, KPNA2, IPO7 or TNPO1.

Mutagenesis

156

1

C → A: Abolishes binding to KPNB1, KPNA2, IPO7 and TNPO1 and nuclear localization. Ref.14

Mutagenesis

161

1

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. Ref.14

Mutagenesis

170

1

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. Ref.14

Mutagenesis

182

1

C → A: Impairs binding to KPNB1, IPO7 and TNPO1 and abolishes binding to KPNA2. Localizes to cytoplasm and nucleus. Ref.14

Mutagenesis

187

1

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. Ref.14

Mutagenesis

191

1

R → E: Does not affect binding to KPNB1, KPNA2, IPO7 or TNPO1. Ref.14

Mutagenesis

203

1

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. Ref.26

Mutagenesis

203

1

T → E: Exclusively localizes to the cytoplasm. Reduces capacity to associate with nuclear pore importins. Unable to enter the nucleus. Does not abrogate function. Ref.26

Mutagenesis

210

1

C → A: Impairs binding to KPNB1, IPO7 and TNPO1 and abolishes binding to KPNA2. Localizes to cytoplasm and nucleus. Ref.14

Mutagenesis

215

1

R → E: Impairs binding to KPNB1, KPNA2, IPO7 and TNPO1. No change in subcellular localization. Ref.14

Mutagenesis

220

1

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. Ref.14

Mutagenesis

222

1

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. Ref.14

Mutagenesis

224

1

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. Ref.14

Mutagenesis

232 – 235

4

DVKK → KVEE: Does not affect binding to KPNB1, KPNA2, IPO7 or TNPO1. Ref.14

Mutagenesis

238

1

C → A: Impairs binding to KPNB1 and IPO7 and abolishes binding to KPNA2 and TNPO1 and nuclear localization. Ref.14

Mutagenesis

239

1

Q → E: Does not affect binding to KPNB1, KPNA2, IPO7, TNPO1 or DNA. Ref.14

Mutagenesis

246

1

S → A: Decreases repression activity on E-cadherin/CDH1, occludin and aromatase promoters. Preferentially localizes to the cytoplasm. Abolishes phosphorylation by PAK1. Ref.9

Sequence conflict

46

1

P → L in BAG36039. Ref.4

Sequence conflict

154

1

F → S in AAF32527. Ref.7

Secondary structure

1

.

.

.

264

Helix Strand Turn

Details...

Helix

3 – 5

3

Sequences

	Sequence		Length	Mass (Da)
	O95863 [UniParc]. Last modified December 1, 2000. Version 2. Checksum: 70E298C9BB154115	FASTA	264	29,083
	10 20 30 40 50 60 MPRSFLVRKP SDPNRKPNYS ELQDSNPEFT FQQPYDQAHL LAAIPPPEIL NPTASLPMLI 70 80 90 100 110 120 WDSVLAPQAQ PIAWASLRLQ ESPRVAELTS LSDEDSGKGS QPPSPPSPAP SSFSSTSVSS 130 140 150 160 170 180 LEAEAYAAFP GLGQVPKQLA QLSEAKDLQA RKAFNCKYCN KEYLSLGALK MHIRSHTLPC 190 200 210 220 230 240 VCGTCGKAFS RPWLLQGHVR THTGEKPFSC PHCSRAFADR SNLRAHLQTH SDVKKYQCQA 250 260 CARTFSRMSL LHKHQESGCS GCPR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Down-regulation of promoter 1.3 activity of the human aromatase gene in breast tissue by zinc-finger protein, snail (SnaH)." Okubo T., Truong T.K., Yu B., Itoh T., Zhao J., Grube B., Zhou D., Chen S. Cancer Res. 61:1338-1346(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-118. Tissue: Mammary gland.
[2]	"Characterisation of the human snail (SNAI1) gene and exclusion as a major disease gene in craniosynostosis." Twigg S.R., Wilkie A.O.M. Hum. Genet. 105:320-326(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Genomic organization, expression, and chromosome location of the human SNAIL gene (SNAI1) and a related processed pseudogene (SNAI1P)." Paznekas W.A., Okajima K., Schertzer M., Wood S., Jabs E.W. Genomics 62:42-49(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Teratocarcinoma.
[5]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[7]	"The transcription factor Snail is a repressor of E-cadherin gene expression in epithelial tumour cells." Batlle E., Sancho E., Franci C., Dominguez D., Monfar M., Baulida J., Garcia de Herreros A. Nat. Cell Biol. 2:84-89(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-172, FUNCTION, TISSUE SPECIFICITY.
[8]	"Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition." Zhou B.P., Deng J., Xia W., Xu J., Li Y.M., Gunduz M., Hung M.C. Nat. Cell Biol. 6:931-940(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GSK3B AND BTRC, PHOSPHORYLATION BY GSK3B, UBIQUITINATION BY BTRC, MUTAGENESIS OF SER-96; SER-100; SER-107; SER-111; SER-115 AND SER-119, SUBCELLULAR LOCATION.
[9]	"Pak1 phosphorylation of snail, a master regulator of epithelial-to-mesenchyme transition, modulates snail's subcellular localization and functions." Yang Z., Rayala S., Nguyen D., Vadlamudi R.K., Chen S., Kumar R. Cancer Res. 65:3179-3184(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-246 BY PAK1, MUTAGENESIS OF SER-246.
[10]	"A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor progression." Peinado H., Del Carmen Iglesias-de la Cruz M., Olmeda D., Csiszar K., Fong K.S., Vega S., Nieto M.A., Cano A., Portillo F. EMBO J. 24:3446-3458(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH LOXL2 AND LOXL3, MUTAGENESIS OF LYS-9; LYS-16; LYS-98 AND LYS-137.
[11]	"Zinc finger domain of Snail functions as a nuclear localization signal for importin beta-mediated nuclear import pathway." Yamasaki H., Sekimoto T., Ohkubo T., Douchi T., Nagata Y., Ozawa M., Yoneda Y. Genes Cells 10:455-464(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH KPNB1.
[12]	"Wnt-dependent regulation of the E-cadherin repressor snail." Yook J.I., Li X.Y., Ota I., Fearon E.R., Weiss S.J. J. Biol. Chem. 280:11740-11748(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH GSK3B AND BTRC, PHOSPHORYLATION AT SER-104 AND SER-107, MUTAGENESIS OF SER-96; SER-104 AND SER-107.
[13]	"Ajuba LIM proteins are snail/slug corepressors required for neural crest development in Xenopus." Langer E.M., Feng Y., Zhaoyuan H., Rauscher F.J. III, Kroll K.L., Longmore G.D. Dev. Cell 14:424-436(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LIMD1 AND AJUBA.
[14]	"Characterization of Snail nuclear import pathways as representatives of C2H2 zinc finger transcription factors." Mingot J.M., Vega S., Maestro B., Sanz J.M., Nieto M.A. J. Cell Sci. 122:1452-1460(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KPNA2; KPNB1; TNPO1 AND IPO7, MUTAGENESIS OF 151-ARG-LYS-152; CYS-156; LYS-161; LYS-170; CYS-182; LYS-187; ARG-191; CYS-210; ARG-215; ARG-220; ASN-222; ARG-224; 232-ASP--LYS-235; CYS-238 AND GLN-239.
[15]	"Snail1 is stabilized by O-GlcNAc modification in hyperglycaemic condition." Park S.Y., Kim H.S., Kim N.H., Ji S., Cha S.Y., Kang J.G., Ota I., Shimada K., Konishi N., Nam H.W., Hong S.W., Yang W.H., Roth J., Yook J.I., Cho J.W. EMBO J. 29:3787-3796(2010) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT SER-112.
[16]	"Snail associates with EGR-1 and SP-1 to upregulate transcriptional activation of p15INK4b." Hu C.T., Chang T.Y., Cheng C.C., Liu C.S., Wu J.R., Li M.C., Wu W.S. FEBS J. 277:1202-1218(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH EGR1, INDUCTION.
[17]	"p53 inhibits tumor cell invasion via the degradation of snail protein in hepatocellular carcinoma." Lim S.O., Kim H., Jung G. FEBS Lett. 584:2231-2236(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TP53 AND MDM2, UBIQUITINATION BY MDM2.
[18]	"The hypoxia-controlled FBXL14 ubiquitin ligase targets SNAIL1 for proteasome degradation." Vinas-Castells R., Beltran M., Valls G., Gomez I., Garcia J.M., Montserrat-Sentis B., Baulida J., Bonilla F., de Herreros A.G., Diaz V.M. J. Biol. Chem. 285:3794-3805(2010) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION BY FBXL14 AND BTRC, INTERACTION WITH FBXL14, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-98; LYS-137 AND LYS-146.
[19]	"Phosphorylation of serine 11 and serine 92 as new positive regulators of human Snail1 function: potential involvement of casein kinase-2 and the cAMP-activated kinase protein kinase A." MacPherson M.R., Molina P., Souchelnytskyi S., Wernstedt C., Martin-Perez J., Portillo F., Cano A. Mol. Biol. Cell 21:244-253(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH CSNK2A1, PHOSPHORYLATION AT SER-11; SER-82; SER-92; SER-104 AND SER-107, MUTAGENESIS OF SER-11; SER-92; SER-104 AND SER-107.
[20]	"Role of CK1 in GSK3beta-mediated phosphorylation and degradation of snail." Xu Y., Lee S.H., Kim H.S., Kim N.H., Piao S., Park S.H., Jung Y.S., Yook J.I., Park B.J., Ha N.C. Oncogene 29:3124-3133(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CSNK1E, PHOSPHORYLATION BY CSNK1E AND GSK3B, PHOSPHORYLATION AT SER-96, MUTAGENESIS OF SER-96; SER-100; SER-104 AND SER-107.
[21]	"Requirement of the histone demethylase LSD1 in Snai1-mediated transcriptional repression during epithelial-mesenchymal transition." Lin T., Ponn A., Hu X., Law B.K., Lu J. Oncogene 29:4896-4904(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH KDM1A, MUTAGENESIS OF PRO-2.
[22]	"Notch1 binds and induces degradation of Snail in hepatocellular carcinoma." Lim S.O., Kim H.S., Quan X., Ahn S.M., Kim H., Hsieh D., Seong J.K., Jung G. BMC Biol. 9:83-83(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH NOTCH1 AND MDM2, SUBCELLULAR LOCATION, UBIQUITINATION BY MDM2, MUTAGENESIS OF SER-96 AND SER-100.
[23]	"Importin alpha protein acts as a negative regulator for Snail protein nuclear import." Sekimoto T., Miyamoto Y., Arai S., Yoneda Y. J. Biol. Chem. 286:15126-15131(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KPNB1; KPNA1; KPNA4 AND KPNA2.
[24]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[25]	"Poly(ADP-ribose)-dependent regulation of Snail1 protein stability." Rodriguez M.I., Gonzalez-Flores A., Dantzer F., Collard J., de Herreros A.G., Oliver F.J. Oncogene 30:4365-4372(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PARP1, SUBCELLULAR LOCATION, ADP-RIBOSYLATION BY PARP1.
[26]	"Lats2 kinase potentiates Snail1 activity by promoting nuclear retention upon phosphorylation." Zhang K., Rodriguez-Aznar E., Yabuta N., Owen R.J., Mingot J.M., Nojima H., Nieto M.A., Longmore G.D. EMBO J. 31:29-43(2012) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-203 BY LATS2, MUTAGENESIS OF THR-203.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF125377 mRNA. Translation: AAD17332.1.
AJ245657, AJ245658, AJ245659 Genomic DNA. Translation: CAB52414.1.
AF155233 Genomic DNA. Translation: AAD52986.1.
AF177731 Genomic DNA. Translation: AAD52996.1.
AK313228 mRNA. Translation: BAG36039.1.
AL121712 Genomic DNA. Translation: CAC07340.1.
BC012910 mRNA. Translation: AAH12910.1.
AF131208 mRNA. Translation: AAF32527.1.

IPI

IPI00000757.

RefSeq

NP_005976.2. NM_005985.3.

UniGene

Hs.48029.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2Y48	X-ray	3.00	C	2-21	[»]

ProteinModelPortal

O95863.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-50870N.

IntAct

O95863. 8 interactions.

STRING

9606.ENSP00000244050.

PTM databases

PhosphoSite

O95863.

Proteomic databases

PaxDb

O95863.

PRIDE

O95863.

Protocols and materials databases

DNASU

6615.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000244050; ENSP00000244050; ENSG00000124216.

GeneID

6615.

KEGG

hsa:6615.

UCSC

uc002xuz.3. human.

Organism-specific databases

CTD

6615.

GeneCards

GC20P048599.

HGNC

HGNC:11128. SNAI1.

HPA

CAB005883.

MIM

604238. gene.

neXtProt

NX_O95863.

PharmGKB

PA35977.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5048.

HOGENOM

HOG000261665.

HOVERGEN

HBG007477.

InParanoid

O95863.

KO

K05707.

OMA

PYDQAHL.

OrthoDB

EOG4868D8.

PhylomeDB

O95863.

Gene expression databases

Bgee

O95863.

CleanEx

HS_SNAI1.

Genevestigator

O95863.

GermOnline

ENSG00000124216. Homo sapiens.

Family and domain databases

Gene3D

3.30.160.60. 3 hits.

InterPro

IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]

SMART

SM00355. ZnF_C2H2. 4 hits.
[Graphical view]

PROSITE

PS00028. ZINC_FINGER_C2H2_1. 3 hits.
PS50157. ZINC_FINGER_C2H2_2. 4 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O95863.

GenomeRNAi

6615.

NextBio

25757.

SOURCE

Search...

Entry information

Entry name

SNAI1_HUMAN

Accession

Primary (citable) accession number: O95863
Secondary accession number(s): B2R842 , Q9P113, Q9UBP7, Q9UHH7

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	December 1, 2000
Last modified:	May 1, 2013
This is version 133 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.