UniProtKB - O43623 (SNAI2_HUMAN)
Protein
Zinc finger protein SNAI2
Gene
SNAI2
Organism
Homo sapiens (Human)
Status
Functioni
Transcriptional repressor that modulates both activator-dependent and basal transcription. Involved in the generation and migration of neural crest cells. Plays a role in mediating RAF1-induced transcriptional repression of the TJ protein, occludin (OCLN) and subsequent oncogenic transformation of epithelial cells (By similarity). Represses BRCA2 expression by binding to its E2-box-containing silencer and recruiting CTBP1 and HDAC1 in breast cells. In epidermal keratinocytes, binds to the E-box in ITGA3 promoter and represses its transcription. Involved in the regulation of ITGB1 and ITGB4 expression and cell adhesion and proliferation in epidermal keratinocytes. Binds to E-box2 domain of BSG and activates its expression during TGFB1-induced epithelial-mesenchymal transition (EMT) in hepatocytes. Represses E-Cadherin/CDH1 transcription via E-box elements. Involved in osteoblast maturation. Binds to RUNX2 and SOC9 promoters and may act as a positive and negative transcription regulator, respectively, in osteoblasts. Binds to CXCL12 promoter via E-box regions in mesenchymal stem cells and osteoblasts. Plays an essential role in TWIST1-induced EMT and its ability to promote invasion and metastasis.By similarity6 Publications
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 128 – 150 | C2H2-type 1PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 159 – 181 | C2H2-type 2PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 185 – 207 | C2H2-type 3PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 213 – 235 | C2H2-type 4PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 241 – 264 | C2H2-type 5; atypicalPROSITE-ProRule annotationAdd BLAST | 24 |
GO - Molecular functioni
- chromatin binding Source: Ensembl
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: GO_Central
- DNA-binding transcription repressor activity, RNA polymerase II-specific Source: BHF-UCL
- E-box binding Source: BHF-UCL
- metal ion binding Source: UniProtKB-KW
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: GO_Central
- RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: BHF-UCL
- sequence-specific DNA binding Source: BHF-UCL
- sequence-specific double-stranded DNA binding Source: ARUK-UCL
GO - Biological processi
- aortic valve morphogenesis Source: BHF-UCL
- cartilage morphogenesis Source: Ensembl
- cell migration involved in endocardial cushion formation Source: BHF-UCL
- cellular response to epidermal growth factor stimulus Source: BHF-UCL
- cellular response to ionizing radiation Source: Ensembl
- desmosome disassembly Source: BHF-UCL
- epithelial to mesenchymal transition Source: BHF-UCL
- epithelial to mesenchymal transition involved in endocardial cushion formation Source: BHF-UCL
- epithelium development Source: BHF-UCL
- negative regulation of anoikis Source: BHF-UCL
- negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
- negative regulation of cell adhesion involved in substrate-bound cell migration Source: Ensembl
- negative regulation of cell adhesion mediated by integrin Source: BHF-UCL
- negative regulation of chondrocyte differentiation Source: BHF-UCL
- negative regulation of DNA damage response, signal transduction by p53 class mediator Source: BHF-UCL
- negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
- negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage Source: BHF-UCL
- negative regulation of keratinocyte proliferation Source: BHF-UCL
- negative regulation of stem cell proliferation Source: Ensembl
- negative regulation of transcription by RNA polymerase II Source: BHF-UCL
- negative regulation of vitamin D biosynthetic process Source: BHF-UCL
- negative regulation of vitamin D receptor signaling pathway Source: BHF-UCL
- neural crest cell development Source: BHF-UCL
- Notch signaling involved in heart development Source: BHF-UCL
- Notch signaling pathway Source: BHF-UCL
- osteoblast differentiation Source: UniProtKB
- pigmentation Source: BHF-UCL
- positive regulation of cell migration Source: BHF-UCL
- positive regulation of fat cell differentiation Source: Ensembl
- positive regulation of histone acetylation Source: Ensembl
- regulation of bicellular tight junction assembly Source: BHF-UCL
- regulation of branching involved in salivary gland morphogenesis Source: Ensembl
- regulation of chemokine production Source: BHF-UCL
- regulation of osteoblast differentiation Source: BHF-UCL
- regulation of transcription, DNA-templated Source: GO_Central
- roof of mouth development Source: Ensembl
- sensory perception of sound Source: BHF-UCL
- white fat cell differentiation Source: Ensembl
Keywordsi
Molecular function | Developmental protein, DNA-binding, Repressor |
Biological process | Transcription, Transcription regulation |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | O43623 |
Reactomei | R-HSA-8943724, Regulation of PTEN gene transcription |
SIGNORi | O43623 |
Names & Taxonomyi
Protein namesi | Recommended name: Zinc finger protein SNAI2Alternative name(s): Neural crest transcription factor Slug Protein snail homolog 2 |
Gene namesi | Name:SNAI2 Synonyms:SLUG, SLUGH |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:11094, SNAI2 |
MIMi | 602150, gene |
neXtProti | NX_O43623 |
VEuPathDBi | HostDB:ENSG00000019549.8 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Other locations
Note: Observed in discrete foci in interphase nuclei. These nuclear foci do not overlap with the nucleoli, the SP100 and the HP1 heterochromatin or the coiled body, suggesting SNAI2 is associated with active transcription or active splicing regions.
Nucleus
- nuclear chromatin Source: ARUK-UCL
- nucleoplasm Source: Reactome
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Involvement in diseasei
Waardenburg syndrome 2D (WS2D)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionWS2 is a genetically heterogeneous, autosomal dominant disorder characterized by sensorineural deafness, pigmentary disturbances, and absence of dystopia canthorum. The frequency of deafness is higher in WS2 than in WS1.
Related information in OMIMPiebald trait (PBT)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAutosomal dominant genetic developmental abnormality of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes.
Related information in OMIMMutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 87 | S → A: Increases protein stability. Does not affect repressor activity on E-cadherin/CDH1 promoter. 1 Publication | 1 | |
Mutagenesisi | 92 | S → A: Increases protein stability, nuclear accumulation and repressor activity on E-cadherin/CDH1 promoter; when associated with A-96. 1 Publication | 1 | |
Mutagenesisi | 96 | S → A: Increases protein stability, nuclear accumulation and repressor activity on E-cadherin/CDH1 promoter; when associated with A-92. 1 Publication | 1 | |
Mutagenesisi | 100 | S → A: Increases protein stability and half-life, nuclear accumulation and repressor activity on E-cadherin/CDH1 promoter; when associated with A-104. 1 Publication | 1 | |
Mutagenesisi | 104 | S → A: Increases protein stability and half-life, nuclear accumulation and repressor activity on E-cadherin/CDH1 promoter; when associated with A-100. 1 Publication | 1 | |
Mutagenesisi | 166 | K → E: Abolishes binding to KPNA2, KPNB1 and IPO7 and impairs binding to TMPO1; when associated with E-175. 1 Publication | 1 | |
Mutagenesisi | 175 | K → E: Abolishes binding to KPNA2, KPNB1 and IPO7 and impairs binding to TMPO1; when associated with E-166. 1 Publication | 1 | |
Mutagenesisi | 192 | K → E: Abolishes binding to KPNA2 and impairs binding to KPNB1, IPO7 and TMPO1; when associated with E-196. 1 Publication | 1 | |
Mutagenesisi | 196 | R → E: Abolishes binding to KPNA2 and impairs binding to KPNB1, IPO7 and TMPO1; when associated with E-192. 1 Publication | 1 | |
Mutagenesisi | 225 | R → E: Abolishes binding to KPNA2, KPNB1 and IPO7 and impairs binding to TMPO1; when associated with E-229. 1 Publication | 1 | |
Mutagenesisi | 229 | R → E: Abolishes binding to KPNA2, KPNB1 and IPO7 and impairs binding to TMPO1; when associated with E-225. 1 Publication | 1 |
Keywords - Diseasei
Deafness, Waardenburg syndromeOrganism-specific databases
DisGeNETi | 6591 |
MalaCardsi | SNAI2 |
MIMi | 172800, phenotype 608890, phenotype |
OpenTargetsi | ENSG00000019549 |
Orphaneti | 2884, Piebaldism 895, Waardenburg syndrome type 2 |
PharmGKBi | PA35945 |
Miscellaneous databases
Pharosi | O43623, Tbio |
Genetic variation databases
BioMutai | SNAI2 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000047032 | 1 – 268 | Zinc finger protein SNAI2Add BLAST | 268 |
Post-translational modificationi
GSK3B-mediated phosphorylation results in cytoplasmic localization and degradation.1 Publication
Proteomic databases
EPDi | O43623 |
MassIVEi | O43623 |
PaxDbi | O43623 |
PeptideAtlasi | O43623 |
PRIDEi | O43623 |
ProteomicsDBi | 49085 |
PTM databases
iPTMneti | O43623 |
PhosphoSitePlusi | O43623 |
Expressioni
Tissue specificityi
Expressed in most adult human tissues, including spleen, thymus, prostate, testis, ovary, small intestine, colon, heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Not detected in peripheral blood leukocyte. Expressed in the dermis and in all layers of the epidermis, with high levels of expression in the basal layers (at protein level). Expressed in osteoblasts (at protein level). Expressed in mesenchymal stem cells (at protein level). Expressed in breast tumor cells (at protein level).4 Publications
Gene expression databases
Bgeei | ENSG00000019549, Expressed in tibia and 217 other tissues |
ExpressionAtlasi | O43623, baseline and differential |
Genevisiblei | O43623, HS |
Organism-specific databases
HPAi | ENSG00000019549, Low tissue specificity |
Interactioni
Subunit structurei
Interacts (via SNAG domain) with LIMD1 (via LIM domains), WTIP (via LIM domains) and AJUBA (via LIM domains) (By similarity).
Interacts (via zinc fingers) with KPNA2, KPNB1, and TNPO1. May interact (via zinc fingers) with IPO7.
By similarity1 PublicationBinary interactionsi
Hide detailsO43623
Protein-protein interaction databases
BioGRIDi | 112476, 38 interactors |
IntActi | O43623, 5 interactors |
STRINGi | 9606.ENSP00000380034 |
Miscellaneous databases
RNActi | O43623, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 20 | SNAG domainBy similarityAdd BLAST | 20 |
Domaini
Repression activity depends on the C-terminal DNA-binding zinc fingers and on the N-terminal repression domain.
Sequence similaritiesi
Belongs to the snail C2H2-type zinc-finger protein family.Curated
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 128 – 150 | C2H2-type 1PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 159 – 181 | C2H2-type 2PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 185 – 207 | C2H2-type 3PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 213 – 235 | C2H2-type 4PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 241 – 264 | C2H2-type 5; atypicalPROSITE-ProRule annotationAdd BLAST | 24 |
Keywords - Domaini
Repeat, Zinc-fingerPhylogenomic databases
eggNOGi | KOG2462, Eukaryota |
GeneTreei | ENSGT00940000154511 |
HOGENOMi | CLU_002678_42_3_1 |
InParanoidi | O43623 |
OMAi | HFNSAKK |
OrthoDBi | 1318335at2759 |
PhylomeDBi | O43623 |
TreeFami | TF315515 |
Family and domain databases
InterProi | View protein in InterPro IPR036236, Znf_C2H2_sf IPR013087, Znf_C2H2_type |
Pfami | View protein in Pfam PF00096, zf-C2H2, 5 hits |
SMARTi | View protein in SMART SM00355, ZnF_C2H2, 5 hits |
SUPFAMi | SSF57667, SSF57667, 4 hits |
PROSITEi | View protein in PROSITE PS00028, ZINC_FINGER_C2H2_1, 4 hits PS50157, ZINC_FINGER_C2H2_2, 5 hits |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
O43623-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MPRSFLVKKH FNASKKPNYS ELDTHTVIIS PYLYESYSMP VIPQPEILSS
60 70 80 90 100
GAYSPITVWT TAAPFHAQLP NGLSPLSGYS SSLGRVSPPP PSDTSSKDHS
110 120 130 140 150
GSESPISDEE ERLQSKLSDP HAIEAEKFQC NLCNKTYSTF SGLAKHKQLH
160 170 180 190 200
CDAQSRKSFS CKYCDKEYVS LGALKMHIRT HTLPCVCKIC GKAFSRPWLL
210 220 230 240 250
QGHIRTHTGE KPFSCPHCNR AFADRSNLRA HLQTHSDVKK YQCKNCSKTF
260
SRMSLLHKHE ESGCCVAH
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A1X7SC17 | A0A1X7SC17_HUMAN | Zinc finger protein SNAI2 | SNAI2 | 89 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 126 | E → K in BAD97088 (Ref. 5) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_069163 | 31 | P → T. Corresponds to variant dbSNP:rs11544360Ensembl. | 1 | |
Natural variantiVAR_009873 | 119 | D → E in a patient with neural tube defects. 1 PublicationCorresponds to variant dbSNP:rs748917911Ensembl. | 1 | |
Natural variantiVAR_069164 | 234 | T → I. Corresponds to variant dbSNP:rs13280993Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF042001 Genomic DNA Translation: AAC34288.1 AF084243 Genomic DNA Translation: AAD55240.1 AK312661 mRNA Translation: BAG35543.1 AK223368 mRNA Translation: BAD97088.1 CH471068 Genomic DNA Translation: EAW86700.1 BC014890 mRNA Translation: AAH14890.1 BC015895 mRNA Translation: AAH15895.1 |
CCDSi | CCDS6146.1 |
RefSeqi | NP_003059.1, NM_003068.4 |
Genome annotation databases
Ensembli | ENST00000020945; ENSP00000020945; ENSG00000019549 |
GeneIDi | 6591 |
KEGGi | hsa:6591 |
UCSCi | uc003xqp.5, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF042001 Genomic DNA Translation: AAC34288.1 AF084243 Genomic DNA Translation: AAD55240.1 AK312661 mRNA Translation: BAG35543.1 AK223368 mRNA Translation: BAD97088.1 CH471068 Genomic DNA Translation: EAW86700.1 BC014890 mRNA Translation: AAH14890.1 BC015895 mRNA Translation: AAH15895.1 |
CCDSi | CCDS6146.1 |
RefSeqi | NP_003059.1, NM_003068.4 |
3D structure databases
SMRi | O43623 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 112476, 38 interactors |
IntActi | O43623, 5 interactors |
STRINGi | 9606.ENSP00000380034 |
PTM databases
iPTMneti | O43623 |
PhosphoSitePlusi | O43623 |
Genetic variation databases
BioMutai | SNAI2 |
Proteomic databases
EPDi | O43623 |
MassIVEi | O43623 |
PaxDbi | O43623 |
PeptideAtlasi | O43623 |
PRIDEi | O43623 |
ProteomicsDBi | 49085 |
Protocols and materials databases
Antibodypediai | 3182, 961 antibodies |
CPTCi | O43623, 2 antibodies |
DNASUi | 6591 |
Genome annotation databases
Ensembli | ENST00000020945; ENSP00000020945; ENSG00000019549 |
GeneIDi | 6591 |
KEGGi | hsa:6591 |
UCSCi | uc003xqp.5, human |
Organism-specific databases
CTDi | 6591 |
DisGeNETi | 6591 |
GeneCardsi | SNAI2 |
HGNCi | HGNC:11094, SNAI2 |
HPAi | ENSG00000019549, Low tissue specificity |
MalaCardsi | SNAI2 |
MIMi | 172800, phenotype 602150, gene 608890, phenotype |
neXtProti | NX_O43623 |
OpenTargetsi | ENSG00000019549 |
Orphaneti | 2884, Piebaldism 895, Waardenburg syndrome type 2 |
PharmGKBi | PA35945 |
VEuPathDBi | HostDB:ENSG00000019549.8 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2462, Eukaryota |
GeneTreei | ENSGT00940000154511 |
HOGENOMi | CLU_002678_42_3_1 |
InParanoidi | O43623 |
OMAi | HFNSAKK |
OrthoDBi | 1318335at2759 |
PhylomeDBi | O43623 |
TreeFami | TF315515 |
Enzyme and pathway databases
PathwayCommonsi | O43623 |
Reactomei | R-HSA-8943724, Regulation of PTEN gene transcription |
SIGNORi | O43623 |
Miscellaneous databases
BioGRID-ORCSi | 6591, 18 hits in 899 CRISPR screens |
GeneWikii | SNAI2 |
GenomeRNAii | 6591 |
Pharosi | O43623, Tbio |
PROi | PR:O43623 |
RNActi | O43623, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000019549, Expressed in tibia and 217 other tissues |
ExpressionAtlasi | O43623, baseline and differential |
Genevisiblei | O43623, HS |
Family and domain databases
InterProi | View protein in InterPro IPR036236, Znf_C2H2_sf IPR013087, Znf_C2H2_type |
Pfami | View protein in Pfam PF00096, zf-C2H2, 5 hits |
SMARTi | View protein in SMART SM00355, ZnF_C2H2, 5 hits |
SUPFAMi | SSF57667, SSF57667, 4 hits |
PROSITEi | View protein in PROSITE PS00028, ZINC_FINGER_C2H2_1, 4 hits PS50157, ZINC_FINGER_C2H2_2, 5 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SNAI2_HUMAN | |
Accessioni | O43623Primary (citable) accession number: O43623 Secondary accession number(s): B2R6P6, Q53FC1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 1, 2000 |
Last sequence update: | June 1, 1998 | |
Last modified: | February 10, 2021 | |
This is version 203 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 8
Human chromosome 8: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families