Description: Homo sapiens adrenoceptor beta 2, surface (ADRB2), mRNA. RefSeq Summary (NM_000024): This gene encodes beta-2-adrenergic receptor which is a member of the G protein-coupled receptor superfamily. This receptor is directly associated with one of its ultimate effectors, the class C L-type calcium channel Ca(V)1.2. This receptor-channel complex also contains a G protein, an adenylyl cyclase, cAMP-dependent kinase, and the counterbalancing phosphatase, PP2A. The assembly of the signaling complex provides a mechanism that ensures specific and rapid signaling by this G protein-coupled receptor. This receptor is also a transcription regulator of the alpha-synuclein gene, and together, both genes are believed to be associated with risk of Parkinson's Disease. This gene is intronless. Different polymorphic forms, point mutations, and/or downregulation of this gene are associated with nocturnal asthma, obesity, type 2 diabetes and cardiovascular disease. [provided by RefSeq, Oct 2019]. Transcript (Including UTRs) Position: hg19 chr5:148,206,156-148,208,197 Size: 2,042 Total Exon Count: 1 Strand: + Coding Region Position: hg19 chr5:148,206,395-148,207,636 Size: 1,242 Coding Exon Count: 1
ID:ADRB2_HUMAN DESCRIPTION: RecName: Full=Beta-2 adrenergic receptor; AltName: Full=Beta-2 adrenoreceptor; Short=Beta-2 adrenoceptor; FUNCTION: Beta-adrenergic receptors mediate the catecholamine- induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine. SUBUNIT: Binds SLC9A3R1 and GPRASP1. Interacts with ARRB1 and ARRB2. Interacts with SRC, USP20 and USP33. Interacts with VHL; the interaction, which is increased on hydroxylation of ADRB2, ubiquitinates ADRB2 leading to its degradation. Interacts with EGLN3; the interaction hydroxylates ADRB2 facilitating VHL-E3 ligase-mediated ubiquitination. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. Note=Colocalizes with VHL at the cell membrane. PTM: Palmitoylated; may reduce accessibility of Ser-345 and Ser- 346 by anchoring Cys-341 to the plasma membrane. Agonist stimulation promotes depalmitoylation and further allows Ser-345 and Ser-346 phosphorylation. PTM: Phosphorylated by PKA and BARK upon agonist stimulation, which mediates homologous desensitization of the receptor. PKA- mediated phosphorylation seems to facilitate phosphorylation by BARK. Phosphorylated upon DNA damage, probably by ATM or ATR. PTM: Phosphorylation of Tyr-141 is induced by insulin and leads to supersensitization of the receptor. PTM: Polyubiquitinated. Agonist-induced ubiquitination leads to sort internalized receptors to the lysosomes for degradation. Deubiquitination by USP20 and USP33, leads to ADRB2 recycling and resensitization after prolonged agonist stimulation. USP20 and USP33 are constitutively associated and are dissociated immediately after agonist stimulation. Ubiquitination by the VHL- E3 ligase complex is oxygen-dependent. PTM: Hydroxylation by EGLN3 occurs only under normoxia and increases the interaction with VHL and the subsequent ubiquitination and degradation of ADRB2. POLYMORPHISM: The Gly-16 allele is overrepresented in individuals affected by nocturnal asthma as compared to controls, and appears to be an important genetic factor in the expression of this asthmatic phenotype. SIMILARITY: Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB2 sub-subfamily. SEQUENCE CAUTION: Sequence=BAD96745.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ADRB2"; WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/adrb2/";
asthma Dai, L. M. et al. 2004, [Relationship between the locus 16 geontype of beta 2 adrenergic receptor and the nocturnal asthma phenotype], Sichuan da xue xue bao Yi xue ban. 2004 Jan;35(1):32-4.
[PubMed 14981808]
The Gly16 polymorphism of beta 2 AR appears to be associated with nocturnal asthma.
asthma Gao, J. M. et al. 2002, [Association of polymorphism of human beta 2-adrenergic receptor gene and bronchial asthma], Zhongguo yi xue ke xue yuan xue bao Acta Academiae Medicinae Sinicae. 2002 Dec;24(6):626-31.
[PubMed 12905693]
Gly16 homozygous beta 2AR was associated with asthma susceptibility in Chinese patients with Han ethnic nearby Beijing region, and Gly16 homozygous beta 2AR was associated significantly with nocturnal asthma. Glu27 homozygous beta 2AR was related to hyper-bronchial reactivity of asthmatics.
asthma Gao, G. et al. 2000, [Study on beta 2 adrenergic receptor genetic polymorphisms in asthmatics in the people of the Han nationality of northern China], Zhonghua jie he he hu xi za zhi. 2000 Feb;23(2):93-7.
[PubMed 11778498]
These results suggest that beta 2-AR 16 locus genetic polymorphism is correlated with asthma severity in the people of the Han nationality of northern China.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P07550
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
