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FLASH GENE
Symbol SOX2 contributors: mct/shn - updated : 01-03-2016
HGNC name SRY (sex determining region Y)-box 2
HGNC id 11195
Corresponding disease
ANOP3 anophthalmos, 3, syndromic
Location 3q26.33      Physical location : 181.429.721 - 181.432.221
Synonym name
  • transcription factor SOX2
  • SRY-related HMG-box gene 2
  • transcription factor SOX2
  • Synonym symbol(s) MGC2413, MCOPS3
    DNA
    TYPE functioning gene
    STRUCTURE 2.51 kb     1 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D3S3662 - D3S1232 - SOX2 - D3S1618 - D3S3609 - qter
    Physical map
    GNB4 21q22.3 guanine nucleotide binding protein (G protein), beta polypeptide 4 BAF53A 3q27.1 guanine nucleotide binding protein (G protein), beta polypeptide 4 MRPL47 3q27.1 mitochondrial ribosomal protein L47 NDUFB5 3q27.1 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 5, 16kDa USP13 3q26.2-q26.3 ubiquitin specific protease 13 (isopeptidase T-3) PEX5R 3q27.1 Pex5p-related protein LOC391593 3 similar to Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) (38 kDa BFA-dependent ADP-ribosylation substrate) (BARS-38) LOC131054 3q27.2 similar to RalA binding protein 1 (RalBP1) (Ral interacting protein 1) (76-kDa Ral-interacting protein) (Dinitrophenyl S-glutathione ATPase) (DNP-SG ATPase) TTC14 3q27.2 tetratricopeptide repeat domain 14 DKFZp434A128 3q27.2 hypothetical protein DKFZp434A128 LOC389178 3 similar to RING finger protein 13 LOC391594 3 similar to KIAA1552 protein LOC391595 3 similar to 60S ribosomal protein L32 FXR1 3q28 fragile X mental retardation, autosomal homolog 1 LOC131118 LOC391596 3 similar to 60S ribosomal protein L7a (Surfeit locus protein 3) (PLA-X polypeptide) SOX2 3q26.3-q27 SRY (sex determining region Y)-box 2 LOC391597 3 similar to ribosomal protein L7-like 1 ATP11B 3q27 ATPase, Class VI, type 11B RP42 3q26.3 RP42 homolog MCCC1 3q25-q27 methylcrotonoyl-Coenzyme A carboxylase 1 (alpha) LAMP3 3q27 lysosomal-associated membrane protein 3 RNU3P4 3q27.3 RNA, U3 small nucleolar pseudogene 4 KIAA0861 3q27.3 Rho family guanine-nucleotide exchange factor B3GNT5 3q28 UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 5 KLHL6 3q27.3 kelch-like 6 (Drosophila) DRE1 3q27.3 DRE1 protein FLJ10201 3q27.3 hypothetical protein FLJ10201 FLJ12748 3q27.3 hypothetical protein FLJ12748 PSARL 3q27.3 presenilin associated, rhomboid-like LOC391598 3 similar to 40S ribosomal protein SA (P40) (34/67 kDa laminin receptor) (Colon carcinoma laminin-binding protein) (NEM/1CHD4) (Multidrug resistance-associated protein MGr1-Ag) LOC391599 3 similar to cytochrome P450 2P1 ABCC5 3q27 ATP-binding cassette, sub-family C (CFTR/MRP), member 5
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    1 - 2518 - 317 - 2008 18388306
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
    Hearing/Equilibriumear   highly
    Nervousbrain   highly
    Visualeye   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningneuroepithelium  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text
  • developing CNS, lens inducing beta and delta crystallin expression, inner cell mass primitive ectoderm, developing gonad
  • expressed in neural progenitor populations throughout the developing and adult central nervous system and is necessary to maintain their progenitor identity
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an high mobility group (HMG) domain
  • a transactivation domain in the carboxyl terminus (transcription activation)
  • a SOX2 regulatory region 2 (SRR2)and a DNA nuclear targeting sequence
  • (SRR2/DTS working as an ES cell-specific DTS)
    HOMOLOGY
    interspecies ortholog to Sox2, Mus musculus
    ortholog to Sox2, Rattus norvegicus
    ortholog to sox2, Danio rerio
    ortholog to SOX2, Pan troglodytes
    Homologene
    FAMILY
  • SRY-related HMG box family of transcription factors
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • can inhibit beta-catenin-driven reporter gene expression
  • modulator of LINE retroposons promoter activity
  • repressing osteopontin
  • playing crucial and diverse roles in the development, specification, and maintenance of sensory cells within the cochlea
  • dose-dependent regulator of retinal neural progenitor competence
  • centrally situated in inner ear development functioning both as a node, receiving signals from several inputs, including Notch signaling, and as a junction, directing signals to different effectors that apparently play unique roles in sensory development
  • essential roles in early development and are required for the propagation of undifferentiated embryonic stem (ES) cells in culture (
  • regulation of SOX2 dosage is critical for temporal and spatial regulation of retinal progenitor cell differentiation (
  • necessary for the normal development and function of the hypothalamo-pituitary and reproductive axes (
  • role in MUC5AC transcription and in the development of mucinous cancers (
  • plays important roles in growth inhibition through cell-cycle arrest and apoptosis in gastric epithelial cells (
  • important for two crucial processes in lung development: branching morphogenesis and epithelial cell differentiation
  • promotes cell proliferation and tumorigenesis by facilitating the G(1)/S transition and through its transcription regulation of the CCND1 gene in breast cancer cells (
  • necessary for normal esophageal squamous development, promotes differentiation and proliferation of basal tracheal cells and cooperates in induction of pluripotent stem cells
  • lineage-survival oncogene in lung and esophageal squamous cell carcinomas
  • modulating alternative splicing in transitional cell carcinoma, by functioning as a splicing factor
  • may have an important role in adult human Müller stem cells differentiation into retinal neurons in vitro (
  • SOX2 and CHD7 were known to be involved in neural development, and create a SOX2-CHD7-regulated network
  • is required for osteosarcoma cell self renewal, and SOX2 antagonizes the pro-differentiation WNT pathway that can in turn reduce SOX2 expression
  • key player in the maintenance of pluripotency and "stemness"
  • POU5F1, SOX2, and NANOG cooperate with a wide array of cofactors to orchestrate an embryonic stem (ES) cell-specific gene expression program that forms the molecular basis of pluripotency
  • directly regulates a previously unidentified long-range forebrain enhancer to activate SIX3 expression in the rostral diencephalon
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
  • SOX2-FN1 axis is a key pathway in mediating the migration and invasion of ovarian cancer cells
  • a component
    INTERACTION
    DNA
  • binding to sequence-like FGF4 enhancer
  • binds to a conserved promoter region of miR-302 (
  • RNA RNA-binding capability (Tung 2010)
    small molecule
    protein
  • POU2F1, POU5F1
  • OTX2 (coordinate RAX expression in eye development, providing molecular linkages among the genes responsible for ocular malformation)
  • LHX3 (SOX2 is able to activate transcription of the LHX3 promoter)
  • paired box 6, Pax6 (
  • Oct1 and Hoxb1 (
  • binds and activates transcription of the LHX3 proximal promoter in vitro (
  • beta-catenin as the transcription partner for SOX2 and act in synergy in the transcription regulation of CCND1 in breast cancer cells (
  • EYA1
  • ZNF281 directly activate NANOG expression by binding to a site in the promoter in very close proximity to the POU5F1 and SOX2 binding sites
  • SALL1 is expressed in a differentiation-dependent manner and physically interacts with NANOG and SOX2, two components of the core pluripotency network
  • SOX2 and CHD7 physically interact, have overlapping genome-wide binding sites and regulate a set of common target genes including JAG1, GLI3 and MYCN
  • coupled with CHD7 cooperatively regulate target genes that are essential during neural stem cell development
  • connection between SOX2 and BMI1 in maintaining self-renewal and identify BMI1 as a key mediator of SOX2 function
  • involved in the synergistic activation of NANOG, that requires a multisubunit stem cell coactivator complex (SCC)
  • PARP1 regulates SOX2 protein activity (regulation of SOX2 activity by PARP1 is critical for efficient generation of induced pluripotent stem cells)
  • cooperates with POU5F1 to activate downstream target genes by binding to Oct-Sox enhancers
  • SOX2 directly transactivates the ASXL1 promoter, and ASXL1 may be a direct target of SOX2 and may play a role in maintaining the pluripotency of stem cells
  • novel regulatory relationship between the NTRK3 gene and the transcription factor SOX2
  • OTX2 prevents the presumptive RPE region from forming the neural retina (NR) by repressing the expression of both FGF8 and SOX2 which induce the NR cell fate
  • directly up-regulates the expression of BIRC5, which inhibits the mitochondria-dependent apoptotic pathway in NSCs (neural stem cells)
  • genomic redistribution of POU5F1 by alternative partnering with SOX2 and SOX17 is a fundamental regulatory event of endodermal specification
  • fine balance between SOX2 and CDX2 expression in the gastrointestinal tract is essential for proper development and that ectopic expression of SOX2 may lead to malformations of the gut
  • SIX3 is a SOX2 transcriptional target
  • SOX2 regulated the transcription of PQBP1 in neural stem progenitor cells (NSPCs)
  • direct physical interaction between NANOG and SOX2 regulates embryonic stem cell self-renewal
  • IL6 induced the lineage commitment and stemness loss in multipotent cells by decreasing SOX2 expression
  • ACTL6A could interact with NANOG and SOX2 and promote NANOG binding to pluripotency genes such as POU5F1 and SOX2
  • MSX2 controls mesendoderm lineage commitment by simultaneous suppression of SOX2 and induction of NODAL expression through direct binding and activation of the NODAL promoter
  • binding between DDX17 and SOX2, although this interaction was largely restricted to reporter responsive (RR) cells
  • NOS1 is transported into the nucleus and interacted with SOX2 to form a NOS1-SOX2 complex in neurons at the early stage following glutamate stimulation
  • NACC1 coordinates differentiation by activating POU5F1 and inhibiting both SOX2 and TCF3
  • SOX2 and LEF1 interact with PITX2 to regulate incisor development and stem cell renewal
  • cell & other
    REGULATION
    induced by chordin
    repressed by BMP4
    miR-145 (
    Phosphorylated by by the PI3K/AKT pathway, which enhances Sox2 activity by stabilizing SOX2 protein levels
    ASSOCIATED DISORDERS
    corresponding disease(s) ANOP3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    result in precocious hair cell differentiation and an over production of inner hair cells and these effects are likely mediated through an antagonistic interaction between SOX2 and ATOH1
    tumoral   amplification    
    in small-cell lung cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveovary
    offers crucial molecular insights and promises to develop putative candidate therapeutic interventions in women with ovarian cancer
    cancerbone 
    novel therapeutic strategies based on inhibiting SOX2 or enhancing Wnt signaling for the treatment of osteosarcomas
    ANIMAL & CELL MODELS
  • compound Sox2(beta-geo/DeltaENH) heterozygote mice show important cerebral malformations, with parenchymal loss and ventricle enlargement, and L-dopa-rescuable circling behaviour and epilepsy (
  • absence in Lcc/Lcc mice or reduced expression in YYsb/Ysb mice of the transcription factor SOX2 lead to hearing and balance impairment (
  • Mice heterozygous for a targeted disruption of Sox2 showed abnormal anterior pituitary development with reduced levels of growth hormone, luteinizing hormone, and thyroid-stimulating hormone (
  • SOX2-overexpressing cells exhibit cell-cycle arrest and apoptosis and may be related to gastric carcinogenesis and poor prognosis (
  • knockdown of Sox2 in Human embryonic stem cells results in reduced expression of several key stem cell factors, including Oct4 and Nanog (
  • SOX2 silencing caused human Müller stem cells to rapidly adopt a neural-like morphology and induced apoptosis, suggesting a crucial role of this factor on human Müller stem cells survival in vitro (