SNAI2

SNAI2
Identifiers
Aliases	SNAI2, SLUG, SLUGH1, SNAIL2, WS2D, snail family transcriptional repressor 2, SLUGH
External IDs	OMIM: 602150; MGI: 1096393; HomoloGene: 31127; GeneCards: SNAI2; OMA:SNAI2 - orthologs
Gene location (Human) Chr. Chromosome 8 (human)[1] Band 8q11.21 Start 48,917,598 bp[1] End 48,921,740 bp[1]
Gene location (Mouse) Chr. Chromosome 16 (mouse)[2] Band 16 A1|16 10.07 cM Start 14,523,716 bp[2] End 14,527,249 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in tibia stromal cell of endometrium periodontal fiber seminal vesicula Achilles tendon hair follicle human penis left uterine tube gums parietal pleura Top expressed in condyle fossa conjunctival fornix hair follicle vas deferens calvaria maxillary prominence body of femur left lung lobe molar More reference expression data BioGPS More reference expression data
Gene ontology Molecular function sequence-specific DNA binding DNA binding metal ion binding protein binding nucleic acid binding DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription repressor activity, RNA polymerase II-specific RNA polymerase II transcription regulatory region sequence-specific DNA binding chromatin binding DNA-binding transcription factor activity transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding E-box binding Cellular component cytoplasm nucleus nucleoplasm Biological process Notch signaling pathway negative regulation of vitamin D receptor signaling pathway regulation of transcription, DNA-templated neural crest cell development negative regulation of keratinocyte proliferation regulation of bicellular tight junction assembly positive regulation of cell migration negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage transcription, DNA-templated cellular response to epidermal growth factor stimulus negative regulation of vitamin D biosynthetic process regulation of chemokine production multicellular organism development negative regulation of chondrocyte differentiation negative regulation of DNA damage response, signal transduction by p53 class mediator regulation of osteoblast differentiation osteoblast differentiation canonical Wnt signaling pathway negative regulation of canonical Wnt signaling pathway negative regulation of cell adhesion mediated by integrin negative regulation of anoikis negative regulation of transcription by RNA polymerase II epithelial to mesenchymal transition epithelial to mesenchymal transition involved in endocardial cushion formation cell migration involved in endocardial cushion formation Q14865145 desmosome disassembly pigmentation epithelium development negative regulation of extrinsic apoptotic signaling pathway in absence of ligand aortic valve morphogenesis negative regulation of cell adhesion involved in substrate-bound cell migration response to radiation cell migration positive regulation of histone acetylation negative regulation of apoptotic process positive regulation of fat cell differentiation white fat cell differentiation roof of mouth development cartilage morphogenesis regulation of branching involved in salivary gland morphogenesis cellular response to ionizing radiation negative regulation of stem cell proliferation Notch signaling involved in heart development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6591 20583 Ensembl ENSG00000019549 ENSMUSG00000022676 UniProt O43623 P97469 RefSeq (mRNA) NM_003068 NM_011415 RefSeq (protein) NP_003059 NP_035545 Location (UCSC) Chr 8: 48.92 – 48.92 Mb Chr 16: 14.52 – 14.53 Mb PubMed search [3] [4]
Wikidata
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Zinc finger protein SNAI2 is a transcription factor that in humans is encoded by the SNAI2 gene. It promotes the differentiation and migration of certain cells and has roles in initiating gastrulation.^[5][6][7]

Function

This gene encodes a member of the Snail superfamily of C2H2-type zinc finger transcription factors. The encoded protein acts as a transcriptional repressor that binds to E-box motifs and is also likely to repress E-cadherin transcription in breast carcinoma. This protein is involved in epithelial-mesenchymal transitions and has antiapoptotic activity. It regulates differentiation and migration of neural crest cells along with other genes (e.g. FOXD3, SOX9 and SOX10, BMPs) in embryonic life. Mutations in this gene may be associated with sporadic cases of neural tube defects.^[7][8]

SNAI2 downregulates expression of E-cadherin in premigratory neural crest cells; thus, SNAI2 induces tightly bound epithelial cells to break into a loose mesenchymal phenotype, allowing gastrulation of mesoderm in the developing embryo.^[9][10] Structurally similar to anti-apoptotic Ces-1 in C. elegans, SLUG is a negative regulator of productive cell death in the developing embryo and adults.^[9][11]

Clinical significance

Widely expressed in human tissues, SLUG is most notably absent in peripheral blood leukocytes, adult liver, and both fetal and adult brain tissues.^[11] SLUG plays a role in breast carcinoma as well as leukemia by downregulation of E-cadherin, which supports mesenchymal phenotype by shifting expression from a Type I to Type II cadherin profile.^[11][12] Maintenance of mesenchymal phenotype enables metastasis of tumor cells, though SLUG is expressed in carcinomas regardless to invasiveness.^[9][10][11] A knockout model using chick embryos has also showed inhibition of mesodermal and neural crest delamination; chick embryo Slug gain of function appears to increase neural crest production.^[9] Mutations in Slug are associated with loss of pregnancy during gastrulation in some animals.^[9]

Interactions

Bone morphogenetic proteins (BMPs) precede expression of SLUG and are suspected as the immediate upstream inducers of gene expression.^[10][13]

References

Further reading