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FLASH GENE

Symbol

SNAI2

contributors: mct - updated : 15-02-2017

HGNC name	snail homolog 2 (Drosophila)
HGNC id	11094

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003068 3 - 2101 NP_003059 3 268 - -

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Digestive liver         Endocrine pancreas         Reproductive female system uterus cervix   highly   female system placenta     highly Skin/Tegument skin       predominantly Urinary bladder       moderately   kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow       Homo sapiens Connective adipose     highly Connective bone       Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic progenitor 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
	by directly binding to SNAI2, FBXO28 functions as an E3 ubiquitin ligase that targets the substrate for degradation via ubiquitin proteasome system

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed obesity     may lead to the development of targeted drugs for the treatment of patients with obesity and/or lipodystrophy metabolism lipid   cancer hemopathy   therapeutic benefits for patients after clinical myelosuppressive treatment

ANIMAL & CELL MODELS