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MGP000086

UniProt Annotations

Entry Information
Gene Nameadrenoceptor beta 2, surface
Protein EntryADRB2_HUMAN
UniProt IDP07550
SpeciesHuman
Comments
Comment typeDescription
FunctionBeta-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.
InteractionQ5TCQ9:MAGI3; NbExp=9; IntAct=EBI-491169, EBI-310506; O14745:SLC9A3R1; NbExp=6; IntAct=EBI-491169, EBI-349787; P12931:SRC; NbExp=3; IntAct=EBI-491169, EBI-621482;
PolymorphismThe 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.
PtmHydroxylation by EGLN3 occurs only under normoxia and increases the interaction with VHL and the subsequent ubiquitination and degradation of ADRB2. {ECO:0000269|PubMed:19424180, ECO:0000269|PubMed:19584355}.
PtmPalmitoylated; 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. {ECO:0000269|PubMed:11146000, ECO:0000269|PubMed:17962520, ECO:0000269|PubMed:18547522, ECO:0000269|PubMed:2540197}.
PtmPhosphorylated by PKA and BARK upon agonist stimulation, which mediates homologous desensitization of the receptor. PKA- mediated phosphorylation seems to facilitate phosphorylation by BARK.
PtmPhosphorylation of Tyr-141 is induced by insulin and leads to supersensitization of the receptor. {ECO:0000269|PubMed:8521811}.
PtmPolyubiquitinated. 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. {ECO:0000269|PubMed:19424180}.
Sequence CautionSequence=BAD96745.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
SimilarityBelongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB2 sub-subfamily. {ECO:0000255|PROSITE-ProRule:PRU00521}.
Subcellular LocationCell membrane {ECO:0000269|PubMed:19584355}; Multi-pass membrane protein {ECO:0000269|PubMed:19584355}. Note=Colocalizes with VHL at the cell membrane.
SubunitBinds 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. Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain); the interaction is required when endocytosed to prevent degradation in lysosomes and promote recycling to the plasma membrane. {ECO:0000269|PubMed:10499588, ECO:0000269|PubMed:12142540, ECO:0000269|PubMed:17952055, ECO:0000269|PubMed:17962520, ECO:0000269|PubMed:18547522, ECO:0000269|PubMed:19424180, ECO:0000269|PubMed:19584355, ECO:0000269|PubMed:20733053, ECO:0000269|PubMed:21602791, ECO:0000269|PubMed:7822302, ECO:0000269|PubMed:9388255, ECO:0000269|PubMed:9924018}.
Web ResourceName=SeattleSNPs; URL="http://pga.gs.washington.edu/data/adrb2/";
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