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FLASH GENE
Symbol SNAI2 contributors: mct - updated : 15-02-2017
HGNC name snail homolog 2 (Drosophila)
HGNC id 11094
Corresponding disease
PBT2 piebaldism 2
WS2D Waardenburg syndrome, type 2D
Location 8q11.21      Physical location : 49.830.238 - 49.833.988
Synonym name
  • slug (chicken homolog), zinc finger protein
  • zinc-finger neural crest transcription factor
  • protein snail homolog 2
  • Synonym symbol(s) SLUGH1, SLUG, SNAIL2, WS2D, MGC10182, SLUGH
    DNA
    TYPE functioning gene
    STRUCTURE 3.75 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (TATA box)
    text structure
  • transcriptionally regulated by MYB via MYB binding sites in the 5prime-flanking region and in the first intron of the gene
  • TWIST1 binds to an evolutionarily conserved E-box on the proximate promoter to induce its transcription
  • MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 2101 3 268 - -
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveliver    
    Endocrinepancreas    
    Reproductivefemale systemuteruscervix highly
     female systemplacenta  highly
    Skin/Tegumentskin   predominantly
    Urinarybladder   moderately
     kidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow    Homo sapiens
    Connectiveadipose  highly
    Connectivebone   
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticprogenitor cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, pregnancy
    Text placenta, migratory neural crest cells
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a domain with 20 amino acid residues at its N-terminus known as SNAG domain
  • five C terminal zinc finger motifs, responsible for DNA binding
  • a CtBP1 binding sequence
  • HOMOLOGY
    interspecies ortholog to murine Snai2
    homolog to C. elegans CES1 (evolutionarily conserved)
    Homologene
    FAMILY
  • snail family of C2H2-type zinc finger transcription factors
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • involved in neural tube, mesoderm and neural crest development
  • transcriptional repressor protein implicated to have major role in the oncogenesis and metastasis
  • transcriptional repressor playing a critical role in the development of neural crest-derived cells
  • playing a role in the development of the melanocytes
  • repressor of CDH1 in breast cancer and of VDR in colon cancer
  • involved in the negative regulation of transcription from RNA polymerase II promoter
  • involved in the generation and migration of neural crest
  • cells
  • acting as a negative regulator for BRCA2 gene expression in breast cells
  • acting as a transcriptional repressor that binds to E2-box motif (5'-CACCTG-3')
  • key regulator of the adipocyte differentiation and in white adipose tissu development
  • directly represses cadherin 6 during epithelial-to-mesenchymal transitions of the neural crest
  • key regulator of epithelial-mesenchymal transition
  • combined expression of SNAI2 and SNAI1 is required for endothelial-to-mesenchymal transition in cardiac cushion morphogenesis
  • important modulator of successful wound repair in adult tissue and may be critical for maintaining epidermal integrity in response to chronic injury
  • functions as a novel regulator of osteoblast activity and may be considered a new factor required for osteoblast maturation
  • essential for controlling the transition of hematopoietic stem cell from relative quiescence under steady-state condition to rapid proliferation under stress conditions
  • in epithelial cells, promoting cell survival (a primary function, rather than being acquired concomitantly with EMT, epithelial-mesenchymal transition)
  • regulator of growth and invasion in human gliomas
  • involved in epithelial mesenchymal transition in physiological and in pathological contexts
  • functional relationship between MYB and metastasis-associated SNAI2 in hematopoietic and non-hematopoietic cancer cells
  • TWIST1 and SNAI2 act together to promote epithelial mesenchymal transition and tumor metastasis
  • indirectly elevates the levels of CCND1 in breast cancer cells by repressing the ubiquitin conjugase enzyme UBE2D3
  • represses the UBE2D3 promoter through chromatin remodeling
  • SNAI2 and ZEB1 are important repressors of E-cadherin, contributing to epithelial-mesenchymal transition (EMT) in primary epithelial cancers
  • SNAI1, SNAI2, and TCF3 can promote collective migration during branching morphogenesis of mammary epithelial tissues through key regulators of EMT (epithelial-mesenchymal transition)
  • key regulator of the signals involved in mesodermal induction of neural crest
  • SNAI2, and SOX9 suffice to convert differentiated mammary epithelial cells to stem cells
  • SNAI2 and SOX9, acting in concert, could function as master regulators of the mammary stem cells state
  • like MMP3, the transcriptional activities of SNAI1 and SNAI2 genes were also negatively associated with the DNA methylation status of the first intron regions
  • SNAI1, SNAI2 genes are regulated by DNA methylation and the DNA methylation of first intron were associated with their transcription in EMT/MET processes
  • SOX9 and SNAI2 may play a developmentally conserved role in regulating cell motility
  • CELLULAR PROCESS cell life
    nucleotide, transcription, regulation
    cell migration & motility
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding to E-box motifs
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • CDH1
  • binds to the E2-box sequence of the DNA through its C-terminal zinc-finger domains and then recruits either CtBP1 and or a SNAG-domain binding protein (e.g., Sin3A) as a co-repressor
  • interacting with UBE2D3 (directly represses the promoter of the UBE2D3 gene)
  • association of SNAI2 with CCND1 levels via UBE2D3 is important in the understanding of the complex role played by SNAI2 in the etiology and metastasis of mammary carcinoma
  • positive correlation between CXCL12 signaling and SNAI2 activity, thus corroborating the role of these two proteins in bone cellular context
  • regulated the transcription of MMP17 through direct binding to the E-box located in its proximal promoter
  • PRDX1 regulated the expression of two E-cadherin transcriptional repressors, SNAI1, SNAI2
  • PHF12 interacts directly with SIN3A, which in turn interacts with SNAI2, resulting in recruitment of the HDAC complex to the promoter region of CDH6
  • both phosphorylation, and to a lesser extent SUMOylation, of SOX9 results in a physical interaction between SNAI2 and SOX9, and SOX9 phosphorylation is necessary to cooperate with SNAI2 to trigger neural crest cell delamination
  • HMGA2 positively regulates the SNAI2 expression by directly binding to the regulatory region in SNAI2 promoter
  • VANGL1 induced the expression of the epithelial-mesenchymal transition (EMT) markers (N-cadherin, ZEB1, ZEB2, SNAI1 and SNAI2) as well as the glioma stemness markers (CD133, ALDH1 and EPHB1)
  • FBN1, acts at the downstream of AURKA and BRCA2, promotes ovarian cancer metastasis through the TP53 and SNAI2-associated signaling
  • KRT18 critically contributes to initiating TGFB1-induced EMT via the SMAD2/3 -mediated regulation of SNAI1, SNAI2 expression in breast epithelial cells
  • ZHX1 could contribute to glioblastoma progression via the regulations of TWIST1 and SNAI2
  • IMP3 facilitates the transcription of SNAI2, which is necessary for TAZ nuclear localization and activation, by a mechanism that is also mediated by WNT5B
  • importance of STAMBP in melanoma metastasis by regulating SNAI2
  • by binding SNAI2, PKNOX1 protects it from the proteasomal degradation
  • cell & other
    REGULATION
    activated by dihydrotestosterone and EGF, providing a molecular mechanism by which epithelial cell-specific genes are silenced during prostate cancer development and progression
    activated transcriptionally in accordance with nuclear accumulation of AHR
    induced by p53 upon irradiation, at tha transcriptional level
    POU2F1 (POU2F1 induced the expression of TWIST1, SNAI1, SNAI2 and ZEB1 genes which are involved in the regulation of epithelial-to-mesenchymal transition (EMT)
    Other DNA methylation is one of the molecular mechanisms regulating SNAI1 and SNAI2 genes during EMT/MET process
    ASSOCIATED DISORDERS
    corresponding disease(s) PBT2 , WS2D
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    in sporadic neural tube defects
    tumoral     --over  
    in colon cancer with invasive phenotype
    tumoral     --over  
    in mesenchymal tumours
    constitutional     --low  
    highly and transitory up-regulated during the partial-epithelial-mesenchymal transition EMT phase of tubulogenesis
    tumoral     --over  
    increased glioblastoma cell proliferation and invasion and promoted angiogenesis and glioblastoma growth
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    obesity  
    may lead to the development of targeted drugs for the treatment of patients with obesity and/or lipodystrophy
    metabolismlipid 
    cancerhemopathy 
    therapeutic benefits for patients after clinical myelosuppressive treatment
    ANIMAL & CELL MODELS