O95863 (SNAI1_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 119.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Zinc finger protein SNAI1 Alternative name(s): Protein snail homolog 1 Short name=Protein sna | ||||
| Gene names |
| ||||
| 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
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 | |||||||||||
Helix Strand Turn | |||||||||||
| Helix | 3 – 5 | 3 | |||||||||
Sequences
| ||||||||||||||||||
References
| « Hide '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. 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 |
| ||||||||||||
| 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 |
| ||||||||
| 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. | ||||||||
Relevant documents
| Human chromosome 20 Human chromosome 20: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with