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FLASH GENE
Symbol GJB2 contributors: mct/pgu - updated : 04-09-2017
HGNC name gap junction protein, beta 2, 26kDa
HGNC id 4284
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Hearing/Equilibriumearinnercochlea highly Homo sapiensAdult
Reproductivemale systemmale genital tractepididymis   Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • four putative membrane spanning alpha helices (TM4)
  • N terminal intracellular domain
  • two extracellular loops
  • a VVAA motif of GJB2 in the TM1 is critical for TM1 dimerization, hexamer formation, and channel function
  • a C terminal intracellular domain
  • mono polymer heteromer , hexamer
    HOMOLOGY
    interspecies homolog to C.elegans T23D8.2
    intraspecies homolog to GJB6
    Homologene
    FAMILY
  • connexin family
  • beta-type (group 1) subfamily
  • CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,gap
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    basic FUNCTION
  • oligomerizing to form intercellular channel that are clustered at gap junctions
  • playing a major role in homeostasis of the cortilymph through the epithelial cell system and in the function of the organ of Corti
  • maybe involved in cornified envelope formation
  • play a crucial role in inner ear Ca2+ signaling: as hemichannels, they promote ATP release, sustaining long-range intercellular Ca2+ signals propagation
  • play an important role in lymphatic invasion as well as lymph node and distant metastases in squamous lung cancer and breast cancer
  • both GJB2 and GJB6 play essential roles in normal cochlear functions
  • plays an essential role in the postnatal development of the normal cochlear sensory epithelium, the organ of Corti
  • plays an essential role in the development of the auditory sensory epithelium and its unique developmental functions required for normal hearing is not replaceable by GJB6
  • GJB2, and GJB6 have dramatically different temporal and cellular expression patterns during early postnatal cochlear development
  • GJB2- hemichannels may play a role in Ca(2+) influx into cells under conditions that lead to hemichannel activation, such as ischemic damage
  • appears to be essential for normal development of the auditory sensory epithelium, but may be dispensable during normal hearing
  • in the cochlea, GJB2, GJB6 largely co-assemble into heteromeric gap junctions, which connect adjacent non-sensory epithelial cells
  • presence of non-junctional GJB2/GJB6 oligomers within lipid raft-enriched tricellular junction sites
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS cell to cell transport
    PATHWAY
    metabolism
    signaling sensory transduction/hearing
    a component
  • monomer constituent of the connexon (six subunits including GJA3, GJA8, GJB1, GJB2) and CX30/CX26 heteromer
  • GJB6 homomeric and GJB2/GJB6 heteromeric gap junctions exhibit distinct assembly mechanisms in the cochlea
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • PTK2 modulates radial glia-dependent neuronal migration through GJB2
  • TCF12 functions as a regulator of EMT by affecting the expression of CDH1 as well as that of GJA1 and GJB2
  • GJB2-DNM2 interaction involves the C-terminus of GJB2 and the GTPase effector domain of DNM2, which is of particular importance for the regulation of the endocytic pathway, and DNM2 regulates GJB2 endocytosis and ubiquitination
  • cell & other
    REGULATION
    Other regulated by a Ca2+-dependent control in the expression of inner ear connexins implicated in hereditary deafness GJB2 and GJB6
    ASSOCIATED DISORDERS
    corresponding disease(s) DFNA3 , DFNB1 , KHM2 , KID , HID
    related resource Hereditary Hearing Loss Homepage
    Hereditary Hearing Loss at GeneDis
    The Connexin-deafness homepage
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    increasing cell survival
    tumoral     --low  
    in hepatocellular carcinoma
    Susceptibility
  • to hearing loss with GJB6 deletion associated
  • to hearing impairment
  • Variant & Polymorphism other
  • heterozygote mutation of DFNB1 increasing cell survival
  • variant M34T significantly associated with hearing impairment
  • a heterozygous mutation 32G->A transversion leading to the G11E substitution. Mutated protein shows abnormal properties in protein trafficking and membrane localization
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS