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FLASH GENE
Symbol ZHX2 contributors: mct/npt/pgu - updated : 12-07-2015
HGNC name zinc fingers and homeoboxes 2
HGNC id 18513
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • two Cys(2)-His(2)-type zinc-finger motifs
  • five homeodomains (HDs)
  • mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies homolog to rattus Zhx2
    homolog to murine Zhx2
    intraspecies paralog to ZHX1, ZHX3
    Homologene
    FAMILY
  • ZHX family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • having transcription factor activity
  • regulate podocyte gene expression during the development of nephrotic syndrome
  • ZHX2 contributes to AFP repression in the liver after birth and may also be involved in AFP reactivation in liver cancer
  • ZHX2 and ZHX3 were involved in the transcriptional repression of the hepatocellular cacinoma markers in normal hepatocytes, suggesting that the failure of the ZHX2 and/or ZHX3 expression might be a critical factor in the hepatocellular carcinogenesis
  • may participate in globin regulation and may be important in the normal physiology of erythrocytes
  • ZHX2 is a novel regulator of neural progenitor cell maintenance
  • acts as a transcriptional repressor in cell, and its repressor activity is enhanced by coexpression of an EFNB1 intracellular domain
  • functions as a novel developmental regulator of key genes influencing lipoprotein metabolism
  • ZHX2 promotes macrophage survival and proinflammatory functions in atherosclerotic lesions, thereby contributing to lesion growth
  • ZHX2 plays likely roles in the regulation of bipolar cell subset fate determination during retinal development
  • ZHX2 could inhibit proliferation and promote apoptosis of lung cancer cells by inhibiting MAPK14 signaling pathway
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • form homodimers but heterodimers with ZHX1
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • able to form a heterodimer with ZHX3 via a region containing each HD1(homeodomain)
  • binds to the cytoplasmic domain of EFNB1, which is expressed in cortical neural progenitors and plays a role in neural progenitor cell maintenance
  • ZHX2 suppresses GPC3 transcription by binding with its core promoter and reduced nucleic ZHX2 expression may be involved in GPC3 reactivation inhepatocellular carcinoma (HCC)
  • ZHX2 promoted NFKB1 activation
  • ZHX2 was found as a VHL target, and its hydroxylation allowed VHL to regulate its protein stability
  • ZHX2 protects hepatocytes from abnormal lipid deposition in Non-alcoholic fatty liver disease (NAFLD) through transcriptional repression of LPL, which subsequently retards cell growth and NAFLD-HCC progression
  • podocyte ZHX2 imbalance is a critical factor in glomerular disease, with minimal change disease disparities mediated mostly through ZHX1, and focal segmental glomerulosclerosis deviations through ZHX3 and ZHX2
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    transcriptional deregulation of homeobox gene ZHX2 in Hodgkin lymphoma
    tumoral   translocation    
    aberration with recurrent breakpoints in Hodgkin lymphoma (HL), t(4;8)(q27;q24), which activate PDE5A and repress ZHX2, deregulating apoptosis, differentiation, and STAT1-signaling in HL cells
    tumoral     --low  
    in myeloma patients, compared with peripheral blood lymphocytes
    tumoral     --low  
    is responsible for GPC3 reactivation in hepatocellular carcinoma (HCC)
    tumoral     --over  
    in clear cell Renal cell carcinoma (RCC)
    tumoral     --over  
    high mRNA levels of ZHX2 and ZHX3 correlated with better overall survival in patients with breast cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerurinary 
    is a potential therapeutic target for Clear Cell Renal Cell Carcinoma (PMID: 30026228)
    ANIMAL & CELL MODELS
  • a mutation of Zhx2 carried in BALB/cJ mice is responsible in large part for its relative resistance to atherosclerosis