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FLASH GENE
Symbol ZEB2 contributors: mct/ - updated : 03-04-2015
HGNC name zinc finger E-box binding homeobox 2
HGNC id 14881
Corresponding disease
MOWS Mowat-Wilson syndrome
Location 2q22.3      Physical location : 145.141.941 - 145.277.958
Synonym name
  • SMAD interacting protein 1
  • zinc finger homeobox 1b
  • Synonym symbol(s) SIP1, SMADIP1, KIAA0569, ZEB-2, ZFHX1B, FLJ42816, HSPC082, SIP-1
    DNA
    TYPE functioning gene
    STRUCTURE 136.02 kb     10 Exon(s)
    MAPPING cloned Y linked N status provisional
    Map cen - D2S129 - D2S2266 - [D2S2149 - KYNU KYNU - D2S122 - D2S132 - GTDC1 - D2S381 - D2S2301 ] - D2S151 - KIF5C - qter
    Text [ZFHX1B ]
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 9243 136.3 1214 - 2005 16314317
    9 - 9171 - 1190 - 2005 16314317
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon highly
    Lymphoid/Immunethymus   highly
    Nervousbrainforebraincerebral cortex highly Homo sapiens
     brainhindbraincerebellum   Homo sapiens
     brainlimbic systemhippocampusdentate gyrus  Homo sapiens
    Olfactory (smell)olfactory bulb     Homo sapiens
    Respiratorylung    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    Nervouspyramidal cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    physiological period fetal, pregnancy
    Text placenta, brain, heart, kidney, liver, spleen
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal cluster of five zinc fingers, containing a previously postulated NuRD binding site, and two zinc-finger clusters at the N- terminal domains (NZF)
  • a homeodomain flanked by two clusters of zinc fingers
  • a SMAD-binding domain (SBD) and a CtBP interaction domain (CID)
  • a homeodomain-like seguence
  • two ZEB2 binding sites that modulate the ability of ZEB2 to downregulate MEOX2 promoter activity
  • C terminal cluster of three zinc fingers, and two zinc-finger clusters at C- terminal domains (CZF)
  • conjugated
    HOMOLOGY
    interspecies ortholog to rattus Zfhx1b predicted
    ortholog to murine Zfhx1b
    Homologene
    FAMILY
  • delta-EF1/ZFH-1 C2H2-type zinc-finger family
  • CATEGORY regulatory , DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • transcriptional repressor of smad target gene
  • playing a role in the patterning of neural crest-derived cells and of the central nervous system but also in the development of midline structures
  • down regulating E-cadherin transcription
  • during epithelial dedifferentiation, represses in a coordinated manner the transcription of genes coding for junctional proteins contributing to the dedifferentiated state
  • may contribute to tumor progression by protecting cancer cells from apoptosis including DNA-damage-dependent apoptotic pathways induced by activated oncogenes
  • modulator of the epithelial-mesenchymal transition, and strongly downregulated by MIR221
  • played an essential role in the GH1-dependent decrease in CDH1 expression
  • essential for transducing the effect of GH1 on CDH1 expression in the glomerular podocyte
  • GH1-dependent increase in ZEB2 plays a role in epithelial-mesenchymal transition in the podocyte and provides a cellular and molecular basis for the role of GH1 in the pathogenesis of diabetic nephropathy
  • controls the transduction properties of heat-sensitive primary sensory neurons and thus thermal pain sensitivity in a novel manner via coordinated changes in DRG-neuron voltage-gated ion channels
  • regulates both early and late mast cell responses
  • transcription factor ZEB2 controls the expression of molecules thereby regulating signaling in mast cells
  • balance between ZEB2 and KLF4 protein levels is important for the modulation of CDH1 expression
  • is involved in the development of primary sensory dorsal root ganglia (DRG) neurons
  • plays a major role in reprogramming the lens vesicle away from a surface ectoderm cell fate towards that necessary for the development of a transparent lens, demonstrating that ZEB2 regulates distinctly different sets of genes in different cellular contexts
  • its expression in the epidermis leads to hyperproliferation due to the combined downregulation of different tight junction proteins compromising the epidermal barrier
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development , neurogenesis
    text negative regulation of transcription
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding to 5'- CACCT-3' in different promoters
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • receptor-mediated activated full length SMADs
  • associates with NuRD through its N-terminal domain (defective NuRD recruitment by mutant ZFHX1B can be a MOWS-causing mechanism)
  • target of GH1 action in the podocyte
  • transcriptional repressor of CDH1 and CDH3 gene expression
  • CDH1 expression is repressed by ZEB2 while it is induced by KLF4
  • NTF3 acts downstream of ZEB2 in cortical postmitotic neurons to control progenitor cell fate through feedback signaling
  • 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)
  • mediates these effects through its direct downstream effector ninein, a microtubule binding protein
  • is transcriptionally activated and functions critically in the GADD45G-induced tumor cell senescence
  • cell & other
    REGULATION
    activated by GH1, that increases expression of ZEB2 in the glomerular podocyte and also decreases CDH1 expression in these cells
    ASSOCIATED DISORDERS
    corresponding disease(s) MOWS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    promotic invasion in eptihelial tumors
    tumoral     --over  
    in bladder tumors and is an independent predictor of poor cancer-specific survival
    constitutional     --over  
    in the epidermis of pemphigus vulgaris
    tumoral     --low  
    of GADD45G-ZEB2 axis may contribute to cellular senescence evasion and hepatocellular carcinoma (HCC) development
    Susceptibility
    Variant & Polymorphism
    Candidate gene biomarker of biological aggressiveness and micrometastases
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerangiogenesis 
    ANIMAL & CELL MODELS
  • Zeb2 null mutation in mice results in early embryonic death with marked neural tube/crest defect