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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

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

General annotation (Comments)

Function	Involved in the epithelial to mesenchymal transition (EMT) and formation and maintenance of embryonic mesoderm By similarity. Binds to 3 E-boxes of the E-cadherin gene promoter and represses its transcription. Ref.6
Subunit structure	Interacts with FBXL14 and GSK3B. Interacts with BTRC; interaction occurs when it is phosphorylated on the destruction motif. Ref.7 Ref.9
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.7 Ref.9
Tissue specificity	Expressed in a variety of tissues with the highest expression in kidney. Expressed in mesenchymal and epithelial cell lines. Ref.6
Post-translational modification	Phosphorylated by GSK3B. Once phosphorylated, it becomes a target for BTRC ubiquitination. Ref.7 Ref.8 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. Ref.7 Ref.9
Sequence similarities	Belongs to the snail C2H2-type zinc-finger protein family. Contains 4 C2H2-type zinc fingers.

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	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	epithelial to mesenchymal transition Inferred from sequence or structural similarity. Source: UniProtKB 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. Source: BHF-UCL negative regulation of apoptotic process Inferred from mutant phenotype. Source: BHF-UCL negative regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of vitamin D biosynthetic process Inferred from direct assay. Source: BHF-UCL osteoblast differentiation Inferred from expression pattern. Source: UniProtKB positive regulation of cell migration Inferred from mutant phenotype. Source: UniProtKB positive regulation of epithelial to mesenchymal transition Inferred from mutant phenotype. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay Ref.7Ref.9. Source: UniProtKB nucleus Inferred from direct assay Ref.7Ref.9. Source: UniProtKB
Molecular function	kinase binding Inferred from physical interaction Ref.7. Source: UniProtKB 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

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

120 – 151

32

Required for FBXL14-triggered degradation

Motif

95 – 100

6

Destruction motif

Amino acid modifications

Modified residue

92

1

Phosphoserine Ref.8

Modified residue

96

1

Phosphoserine Probable

Modified residue

100

1

Phosphoserine Probable

Modified residue

107

1

Phosphoserine Probable

Modified residue

111

1

Phosphoserine Probable

Modified residue

115

1

Phosphoserine Probable

Modified residue

119

1

Phosphoserine Probable

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

118

1

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

VAR_019969

Experimental info

Mutagenesis

96

1

S → A: Lower sensitivity to BTRC-triggered degradation and impaired phosphorylation by GSK3B; 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.7

Mutagenesis

98

1

K → R: No change. Complete loss of sensitivity to FBXL14- and BTRC-triggered degradation; when associated with R-137 and R-146. Ref.9

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. Ref.7

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. Ref.7

Mutagenesis

107

1

S → E: Predominantly localized to the cytoplasm; when associated with E-111; E-115 and E-119. Ref.7

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.7

Mutagenesis

111

1

S → E: Predominantly localized to the cytoplasm; when associated with E-107; E-115 and E-119. Ref.7

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.7

Mutagenesis

115

1

S → E: Predominantly localized to the cytoplasm; when associated with E-107; E-111 and E-119. Ref.7

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.7

Mutagenesis

119

1

S → E: Predominantly localized to the cytoplasm; when associated with E-107; E-111 and E-115. Ref.7

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; when associated with R-98 and R-146. Ref.9

Mutagenesis

146

1

K → R: Lower sensitivity to FBXL14-triggered degradation. Lower sensitivity to FBXL14-triggered degradation; when associated to R-137. Complete loss of sensitivity to FBXL14- and BTRC-triggered degradation; when associated with R-98 and R-137. Ref.9

Sequence conflict

154

1

F → S in AAF32527. Ref.6

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: 11245431] [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: 10543399] [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: 10585766] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"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: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[6]	"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: 10655587] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-172, FUNCTION, TISSUE SPECIFICITY.
[7]	"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: 15448698] [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.
[8]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-92, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"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: 19955572] [Abstract] Cited for: UBIQUITINATION BY FBXL14 AND BTRC, INTERACTION WITH FBXL14, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-98; LYS-137 AND LYS-146.
+	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.
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.

SMR

O95863. Positions 97-264.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-50870N.

IntAct

O95863. 7 interactions.

STRING

O95863.

PTM databases

PhosphoSite

O95863.

Proteomic databases

PRIDE

O95863.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000244050; ENSP00000244050; ENSG00000124216.

GeneID

6615.

KEGG

hsa:6615.

UCSC

uc002xuz.1. 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

prNOG13366.

GeneTree

ENSGT00390000011027.

HOGENOM

HBG713176.

HOVERGEN

HBG007477.

InParanoid

O95863.

OMA

YDQAHLL.

OrthoDB

EOG4868D8.

PhylomeDB

O95863.

Gene expression databases

ArrayExpress

O95863.

Bgee

O95863.

CleanEx

HS_SNAI1.

Genevestigator

O95863.

GermOnline

ENSG00000124216. Homo sapiens.

Family and domain databases

InterPro

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

Gene3D

G3DSA:3.30.160.60. Znf_C2H2/integrase_DNA-bd. 4 hits.

KO

K05707.

Pfam

PF00096. zf-C2H2. 4 hits.
[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

NextBio

25757.

SOURCE

Search...

Entry information

Entry name

SNAI1_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	December 1, 2000
Last modified:	January 25, 2012
This is version 119 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.