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Protein

Zinc finger protein SNAI1

Gene

Snai1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 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 12-O-tetradecanoylphorbol-13-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.2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri156 – 17621C2H2-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri180 – 20223C2H2-type 2PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri210 – 23021C2H2-type 3PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri236 – 25924C2H2-type 4; atypicalPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

  • cartilage morphogenesis Source: MGI
  • cell migration Source: MGI
  • epithelial to mesenchymal transition Source: UniProtKB
  • epithelial to mesenchymal transition involved in endocardial cushion formation Source: BHF-UCL
  • hair follicle morphogenesis Source: MGI
  • left/right pattern formation Source: MGI
  • mesoderm development Source: MGI
  • mesoderm formation Source: UniProtKB
  • negative regulation of cell differentiation involved in embryonic placenta development Source: MGI
  • negative regulation of DNA damage response, signal transduction by p53 class mediator Source: MGI
  • negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage Source: MGI
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • negative regulation of vitamin D biosynthetic process Source: MGI
  • Notch signaling involved in heart development Source: BHF-UCL
  • osteoblast differentiation Source: Ensembl
  • palate development Source: MGI
  • positive regulation of cell migration Source: BHF-UCL
  • positive regulation of epithelial to mesenchymal transition Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • regulation of bicellular tight junction assembly Source: MGI
  • regulation of transcription from RNA polymerase II promoter Source: MGI
  • trophoblast giant cell differentiation Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Zinc finger protein SNAI1
Alternative name(s):
Protein snail homolog 1
Short name:
Protein sna
Gene namesi
Name:Snai1
Synonyms:Sna
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:98330. Snai1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Embryos die early in gestation, exhibiting defects in gastrulation and mesoderm formation. Recessive lethal mutation.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 264264Zinc finger protein SNAI1PRO_0000047030Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei11 – 111PhosphoserineBy similarity
Modified residuei82 – 821PhosphoserineBy similarity
Modified residuei92 – 921PhosphoserineBy similarity
Modified residuei96 – 961Phosphoserine1 Publication
Cross-linki98 – 98Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei100 – 1001Phosphoserine1 Publication
Modified residuei104 – 1041PhosphoserineBy similarity
Modified residuei107 – 1071Phosphoserine1 Publication
Modified residuei111 – 1111Phosphoserine1 Publication
Glycosylationi112 – 1121O-linked (GlcNAc)By similarity
Modified residuei115 – 1151Phosphoserine1 Publication
Modified residuei119 – 1191Phosphoserine1 Publication
Cross-linki137 – 137Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki146 – 146Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei203 – 2031PhosphothreonineBy similarity
Modified residuei246 – 2461PhosphoserineBy similarity

Post-translational modificationi

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-104 positively regulates its function in induction of EMT and/or 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 (By similarity).By similarity
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 p53 is mediated by MDM2 (By similarity).By similarity
O-GlcNAcylation at Ser-112 is enhanced in hyperglycaemic conditions, it opposes phosphorylation by GSK3B, and stabilizes the protein.By similarity
ADP-ribosylation by PARP1 increases protein half-life and may be involved in TGFB-induced SNAI1 up-regulation.By similarity

Keywords - PTMi

ADP-ribosylation, Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ02085.
PRIDEiQ02085.

PTM databases

iPTMnetiQ02085.
PhosphoSiteiQ02085.

Expressioni

Tissue specificityi

While expression is completely absent from non-invasive cell lines, it is high in invasive and metastatic cell types.

Developmental stagei

Postimplantation. Expression is observed in undifferentiated mesoderm and in tissues undergoing EMTs, namely the precursors of the neural crest cells and the primitive streak.1 Publication

Gene expression databases

BgeeiQ02085.
CleanExiMM_SNAI1.
ExpressionAtlasiQ02085. baseline and differential.
GenevisibleiQ02085. MM.

Interactioni

Subunit structurei

Interacts with LOXL2 and LOXL3 (By similarity). Interacts with FBXL14 and GSK3B. Interacts with BTRC; interaction occurs when it is phosphorylated on the destruction motif. Interacts (via SNAG domain) with LIMD1 (via LIM domains), WTIP (via LIM domains) and AJUBA (via LIM domains). 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.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PARP1P098743EBI-6049807,EBI-355676From a different organism.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi203361. 4 interactions.
IntActiQ02085. 1 interaction.
STRINGi10090.ENSMUSP00000050581.

Structurei

3D structure databases

ProteinModelPortaliQ02085.
SMRiQ02085. Positions 116-264.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 2020SNAG domainBy similarityAdd
BLAST
Regioni10 – 4031LATS2 bindingBy similarityAdd
BLAST
Regioni120 – 15132Required for FBXL14-triggered degradationBy similarityAdd
BLAST
Regioni151 – 264114Required for nuclear localization and interaction with KPNB1, NOTCH1 and PARP1By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi95 – 1006Destruction motif

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi90 – 12031Ser-richAdd
BLAST

Sequence similaritiesi

Contains 4 C2H2-type zinc fingers.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri156 – 17621C2H2-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri180 – 20223C2H2-type 2PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri210 – 23021C2H2-type 3PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri236 – 25924C2H2-type 4; atypicalPROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG2462. Eukaryota.
ENOG41106JS. LUCA.
HOGENOMiHOG000261665.
HOVERGENiHBG007477.
InParanoidiQ02085.
KOiK05707.
OMAiQPIGWAS.
OrthoDBiEOG7P2XSG.
PhylomeDBiQ02085.
TreeFamiTF315515.

Family and domain databases

Gene3Di3.30.160.60. 3 hits.
InterProiIPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamiPF00096. zf-C2H2. 1 hit.
PF13912. zf-C2H2_6. 1 hit.
[Graphical view]
SMARTiSM00355. ZnF_C2H2. 4 hits.
[Graphical view]
PROSITEiPS00028. ZINC_FINGER_C2H2_1. 3 hits.
PS50157. ZINC_FINGER_C2H2_2. 4 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q02085-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPRSFLVRKP SDPRRKPNYS ELQDACVEFT FQQPYDQAHL LAAIPPPEVL
60 70 80 90 100
NPAASLPTLI WDSLLVPQVR PVAWATLPLR ESPKAVELTS LSDEDSGKSS
110 120 130 140 150
QPPSPPSPAP SSFSSTSASS LEAEAFIAFP GLGQLPKQLA RLSVAKDPQS
160 170 180 190 200
RKIFNCKYCN KEYLSLGALK MHIRSHTLPC VCTTCGKAFS RPWLLQGHVR
210 220 230 240 250
THTGEKPFSC SHCNRAFADR SNLRAHLQTH SDVKRYQCQA CARTFSRMSL
260
LHKHQESGCS GGPR
Length:264
Mass (Da):29,190
Last modified:October 1, 1996 - v1
Checksum:i52E2061224A18DEB
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti219 – 2191D → V in CAA47675 (PubMed:1483390).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M95604 mRNA. Translation: AAA03481.1.
X67253 mRNA. Translation: CAA47675.1.
BC034857 mRNA. Translation: AAH34857.1.
U95961 Genomic DNA. Translation: AAB58054.1.
CCDSiCCDS17102.1.
PIRiA49149.
RefSeqiNP_035557.1. NM_011427.3.
UniGeneiMm.2093.

Genome annotation databases

EnsembliENSMUST00000052631; ENSMUSP00000050581; ENSMUSG00000042821.
GeneIDi20613.
KEGGimmu:20613.
UCSCiuc008nzy.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M95604 mRNA. Translation: AAA03481.1.
X67253 mRNA. Translation: CAA47675.1.
BC034857 mRNA. Translation: AAH34857.1.
U95961 Genomic DNA. Translation: AAB58054.1.
CCDSiCCDS17102.1.
PIRiA49149.
RefSeqiNP_035557.1. NM_011427.3.
UniGeneiMm.2093.

3D structure databases

ProteinModelPortaliQ02085.
SMRiQ02085. Positions 116-264.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203361. 4 interactions.
IntActiQ02085. 1 interaction.
STRINGi10090.ENSMUSP00000050581.

PTM databases

iPTMnetiQ02085.
PhosphoSiteiQ02085.

Proteomic databases

PaxDbiQ02085.
PRIDEiQ02085.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000052631; ENSMUSP00000050581; ENSMUSG00000042821.
GeneIDi20613.
KEGGimmu:20613.
UCSCiuc008nzy.1. mouse.

Organism-specific databases

CTDi6615.
MGIiMGI:98330. Snai1.

Phylogenomic databases

eggNOGiKOG2462. Eukaryota.
ENOG41106JS. LUCA.
HOGENOMiHOG000261665.
HOVERGENiHBG007477.
InParanoidiQ02085.
KOiK05707.
OMAiQPIGWAS.
OrthoDBiEOG7P2XSG.
PhylomeDBiQ02085.
TreeFamiTF315515.

Miscellaneous databases

NextBioi298979.
PROiQ02085.
SOURCEiSearch...

Gene expression databases

BgeeiQ02085.
CleanExiMM_SNAI1.
ExpressionAtlasiQ02085. baseline and differential.
GenevisibleiQ02085. MM.

Family and domain databases

Gene3Di3.30.160.60. 3 hits.
InterProiIPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamiPF00096. zf-C2H2. 1 hit.
PF13912. zf-C2H2_6. 1 hit.
[Graphical view]
SMARTiSM00355. ZnF_C2H2. 4 hits.
[Graphical view]
PROSITEiPS00028. ZINC_FINGER_C2H2_1. 3 hits.
PS50157. ZINC_FINGER_C2H2_2. 4 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation of Sna, a mouse gene homologous to the Drosophila genes snail and escargot: its expression pattern suggests multiple roles during postimplantation development."
    Smith D.E., del Amo F.F., Gridley T.
    Development 116:1033-1039(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Embryo.
  2. "Cloning and developmental expression of Sna, a murine homologue of the Drosophila snail gene."
    Nieto A.M., Bennett M.F., Sargent M.G., Wilkinson D.G.
    Development 116:227-237(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "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].
    Strain: Czech II.
    Tissue: Lung.
  4. "Genomic organization and chromosomal localization of the mouse snail (Sna) gene."
    Jiang R., Copeland N.G., Gilbert D.J., Jenkins N.A., Gridley T.
    Mamm. Genome 8:686-688(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-27.
    Strain: 129/Sv.
  5. "The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression."
    Cano A., Perez-Moreno M.A., Rodrigo I., Locascio A., Blanco M.J., del Barrio M.G., Portillo F., Nieto M.A.
    Nat. Cell Biol. 2:76-83(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DEVELOPMENTAL STAGE.
  6. "The mouse snail gene encodes a key regulator of the epithelial-mesenchymal transition."
    Carver E.A., Jiang R., Lan Y., Oram K.F., Gridley T.
    Mol. Cell. Biol. 21:8184-8188(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  7. "Phosphorylation regulates the subcellular location and activity of the snail transcriptional repressor."
    Dominguez D., Montserrat-Sentis B., Virgos-Soler A., Guaita S., Grueso J., Porta M., Puig I., Baulida J., Franci C., Garcia de Herreros A.
    Mol. Cell. Biol. 23:5078-5089(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION.
  8. "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; WTIP AND AJUBA.
  9. "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.
  10. "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.
  11. "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: INTERACTION WITH CSNK2A1.
  12. "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.

Entry informationi

Entry nameiSNAI1_MOUSE
AccessioniPrimary (citable) accession number: Q02085
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: February 17, 2016
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.