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FLASH GENE
Symbol ADRB2 contributors: mct - updated : 09-03-2016
HGNC name adrenergic, beta-2-, receptor, surface
HGNC id 286
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a PDZ binding motif
  • C terminus distal to AA 381 does not affect the initial interaction between receptor and beta-arrestin, but its last eight AAs facilitate receptor internalization in concert with ARRB2 (
    • HOMOLOGY
    Homologene
    FAMILY G protein coupled receptor superfamily
    CATEGORY signaling , receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    basic FUNCTION
  • major lipolytic receptor in human fat cell, activating adenylate cyclase
  • ADRB2, ADRA1B in bone cells may play a role in modulation of bone turnover by the sympathetic nervous system
  • seven transmembrane segments (7TM) receptor, polymorphic, with a 5' leader region made of a short ORF, potentially involved in the regulation of cellular ADRBL expression
  • mediating the catecholamine-induced activation of adenylate cyclase through the action of G proteins
  • may be involved in the cardioprotection against ischemic damage, and the cardioprotection may depend on estrogenic environment
  • playing an essential role in signaling and trafficking in cardiac myocytes
  • on the surface of cardiomyocytes mediate distinct effects on cardiac function and the development of heart failure by regulating production of the second messenger cyclic adenosine monophosphate (cAMP)
  • potential involvement in diabetic cardiomyopathy
  • mediates obesity, cardiorespiratory fitness, and insulin resistance
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with NEDD4 (NEDD4 mediates agonist-dependent ubiquitination, lysosomal targeting, and degradation of the ADRB2)
  • ADRB2 is a novel target of PPARgamma transcriptional repression in vascular smooth muscle cells (PPARgamma regulation of ADRB2 signaling is important in the modulation of blood pressure)
  • MARCH2 catalytic activity is not required for its interaction with the ADRB2 and loss of activity creates a “substrate trap” leading to a stable complex formation between the two molecules
  • ADRB2 stimulation suppresses TLR9-dependent IFNA1 secretion in human peripheral blood mononuclear cells
  • interaction between RNF5 and the ADRB2 as well as the prostaglandin D2 receptor (DP)
  • SSTR2 plays a crucial role in modulation of ADRB1 and ADRB2 mediated signaling pathways that are associated with increased intracellular Ca(2+) and cardiac complications
  • ubiquitination by the E3 ligase NEDD4 and deubiquitination by the deubiquitinases USP20 and USP33 have been shown to regulate the lysosomal trafficking and recycling of agonist-activated ADRB2
    • cell & other
    REGULATION
    Other is modified at a second site within the third intracellular loop
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    is potentially implicated in diabetic cardiomyopathy
    constitutional     --over  
    in lymphatic malformations
    constitutional     --over  
    ADRB2, FOLR3 and GSTM1 were upregulated in the monocytes of patients with early onset coronary artery disease
    Susceptibility
  • to nocturnal asthma, to non insulin dependent diabetes
  • to type 2 diabetes mellitus (T2DM) in obese, postmenopausal women
  • to chronic obstructive pulmonary disease (COPD)
    • Variant & Polymorphism SNP , other
  • polymorphism, R16G
  • 27 Glu polymorphism interacting with physical activity to influence female obesity risk
  • Gln27Gln polymorphism increases the risk of non insulin dependent diabetes
  • Arg16Gly influencing the pathophysiology of OAG in Japanese patients
  • ADRB2 haplotypes may mediate insulin action, glucose tolerance, and potentially risk for type 2 diabetes mellitus (T2DM) in obese, postmenopausal women
  • Gly16 allele of ADRB2 predisposes to COPD development but not for exacerbation rates and disease severity
    • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabete  
    ADRB2 agonist ameliorates cardiac dysfunction suggesting that ADRB2 have crucial role in diabetic cardiomyopathy
    ANIMAL & CELL MODELS