P07550 B0LPE4 B2R7X2 O14823 O14824 O14825 O14826 Q4JG18 Q53GA6 Q6GMT4 Q6P4D8 Q8NEQ9 Q96EC3 Q9UCZ0 Q9UCZ1 Q9UCZ2 Q9UCZ3 Q9UH95 Q9UHA1 Q9UMZ5 ADRB2_HUMAN Beta-2 adrenergic receptor Beta-2 adrenoreceptor Beta-2 adrenoceptor ADRB2 ADRB2R B2AR Homo sapiens Human Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Haplorrhini Catarrhini Hominidae Homo Cloning and sequence analysis of the human brain beta-adrenergic receptor. Evolutionary relationship to rodent and avian beta-receptors and porcine muscarinic receptors. NUCLEOTIDE SEQUENCE [MRNA] VARIANT GLN-27 Brain Delineation of the intronless nature of the genes for the human and hamster beta 2-adrenergic receptor and their putative promoter regions. NUCLEOTIDE SEQUENCE [GENOMIC DNA] VARIANTS ARG-16 AND GLN-27 Primary structure of the human beta-adrenergic receptor gene. NUCLEOTIDE SEQUENCE [GENOMIC DNA] VARIANTS ARG-16 AND GLN-27 cDNA for the human beta 2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor. NUCLEOTIDE SEQUENCE [MRNA] VARIANTS ARG-16 AND GLN-27 Structure of the gene for human beta 2-adrenergic receptor: expression and promoter characterization. NUCLEOTIDE SEQUENCE [GENOMIC DNA] VARIANT GLN-27 Mutations in the gene encoding for the beta 2-adrenergic receptor in normal and asthmatic subjects. NUCLEOTIDE SEQUENCE [GENOMIC DNA] VARIANTS ARG-16; GLN-27; MET-34 AND ILE-164 Beta2-adrenergic receptor allele frequencies in the Quechua, a high altitude native population. NUCLEOTIDE SEQUENCE [GENOMIC DNA] VARIANTS GLN-27; LEU-159; PHE-159 AND ARG-375 Blood cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org). NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] VARIANTS ARG-16 AND GLN-27 Heart Complete sequencing and characterization of 21,243 full-length human cDNAs. NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] Brain NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] VARIANT GLN-27 Thyroid NUCLEOTIDE SEQUENCE [GENOMIC DNA] VARIANTS GLN-27 AND CYS-220 NUCLEOTIDE SEQUENCE [GENOMIC DNA] VARIANT GLN-27 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] VARIANTS ARG-16 AND GLN-27 Fetal brain Leukocyte Prostate Site-directed mutagenesis and continuous expression of human beta-adrenergic receptors. Identification of a conserved aspartate residue involved in agonist binding and receptor activation. MUTAGENESIS OF ASP-79 FUNCTION SUBCELLULAR LOCATION Palmitoylation of the human beta 2-adrenergic receptor. Mutation of Cys341 in the carboxyl tail leads to an uncoupled nonpalmitoylated form of the receptor. PALMITOYLATION AT CYS-341 MUTAGENESIS OF CYS-341 Mutation of tyrosine-141 inhibits insulin-promoted tyrosine phosphorylation and increased responsiveness of the human beta 2-adrenergic receptor. MUTAGENESIS OF TYR-141; TYR-350; TYR-354 AND TYR-366 PHOSPHORYLATION AT TYR-141 Arrestin interactions with G protein-coupled receptors. Direct binding studies of wild type and mutant arrestins with rhodopsin, beta 2-adrenergic, and m2 muscarinic cholinergic receptors. INTERACTION WITH ARRB1 AND ARRB2 Clathrin-mediated endocytosis of the beta-adrenergic receptor is regulated by phosphorylation/dephosphorylation of beta-arrestin1. INTERACTION WITH ARRB1 A kinase-regulated PDZ-domain interaction controls endocytic sorting of the beta2-adrenergic receptor. INTERACTION WITH NHERF1 Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes. INTERACTION WITH SRC AND ARRB1 The palmitoylation state of the beta(2)-adrenergic receptor regulates the synergistic action of cyclic AMP-dependent protein kinase and beta-adrenergic receptor kinase involved in its phosphorylation and desensitization. EFFECT OF PALMITOYLATION PHOSPHORYLATION AT SER-345 AND SER-346 MUTAGENESIS OF 345-SER-SER-346 Modulation of postendocytic sorting of G protein-coupled receptors. INTERACTION WITH GPRASP1 ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-246 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS] Embryonic kidney The deubiquitinases USP33 and USP20 coordinate beta2 adrenergic receptor recycling and resensitization. UBIQUITINATION DEUBIQUITINATION BY USP20 AND USP33 INTERACTION WITH USP20 AND USP33 Oxygen-regulated beta(2)-adrenergic receptor hydroxylation by EGLN3 and ubiquitylation by pVHL. INTERACTION WITH EGLN3 AND VHL SUBCELLULAR LOCATION INDUCTION UBIQUITINATION HYDROXYLATION AT PRO-382 AND PRO-395 IDENTIFICATION BY MASS SPECTROMETRY Arrestin domain-containing protein 3 recruits the NEDD4 E3 ligase to mediate ubiquitination of the beta2-adrenergic receptor. UBIQUITINATION SUBCELLULAR LOCATION INTERACTION WITH ARRDC3 SNX27 mediates PDZ-directed sorting from endosomes to the plasma membrane. INTERACTION WITH SNX27 SNX27 mediates retromer tubule entry and endosome-to-plasma membrane trafficking of signalling receptors. INTERACTION WITH SNX27 MARCH2 promotes endocytosis and lysosomal sorting of carvedilol-bound beta(2)-adrenergic receptors. INTERACTION WITH MARCHF2; NEDD4; USP20 AND USP33 SUBCELLULAR LOCATION UBIQUITINATION Insights into beta2-adrenergic receptor binding from structures of the N-terminal lobe of ARRDC3. SUBCELLULAR LOCATION INTERACTION WITH ARRDC3 CNIH4 interacts with newly synthesized GPCR and controls their export from the endoplasmic reticulum. INTERACTION WITH CNIH4 S-Palmitoylation of a Novel Site in the beta2-Adrenergic Receptor Associated with a Novel Intracellular Itinerary. SUBCELLULAR LOCATION PALMITOYLATION AT CYS-265 AND CYS-341 MUTAGENESIS OF CYS-265 AND CYS-341 Crystal structure of the human beta2 adrenergic G-protein-coupled receptor. X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 1-365 IN COMPLEX WITH CARAZOLOL TOPOLOGY High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-365 IN COMPLEX WITH CARAZOLOL AND CHOLESTEROL DISULFIDE BONDS TOPOLOGY PALMITOYLATION AT CYS-341 A specific cholesterol binding site is established by the 2.8 A structure of the human beta2-adrenergic receptor. X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-365 IN COMPLEX WITH TIMOLOL AND CHOLESTEROL DISULFIDE BONDS TOPOLOGY PALMITOYLATION AT CYS-341 Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties. VARIANTS ARG-16 AND GLN-27 CHARACTERIZATION FUNCTION SUBCELLULAR LOCATION Genetic polymorphisms of the beta 2-adrenergic receptor in nocturnal and nonnocturnal asthma. Evidence that Gly16 correlates with the nocturnal phenotype. VARIANT ARG-16 POLYMORPHISM 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. Binds NHERF1 and GPRASP1. Interacts with ARRB1 and ARRB2. Interacts with SRC (PubMed:9924018). Interacts with USP20 and USP33 (PubMed:19424180, PubMed:23166351). 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. Interacts with CNIH4 (PubMed:24405750). Interacts with ARRDC3 (PubMed:20559325, PubMed:25220262). Interacts with NEDD4 (PubMed:23166351). Interacts with MARCHF2 (PubMed:23166351). P07550 P30542 false 5 P07550 P07550 false 4 P07550 P32121 false 3 P07550 Q96B67 false 6 P07550 Q9UII2 false 3 P07550 Q9ULD4-2 false 3 P07550 Q9NSI6-4 false 3 P07550 Q5M9N0-2 false 3 P07550 A0AVK6 false 3 P07550 Q658K8 false 3 P07550 O00472 false 3 P07550 Q15910-2 false 3 P07550 Q15486 false 3 P07550 P61978 false 2 P07550 Q5TCQ9 false 9 P07550 Q99685 false 2 P07550 O14745 false 6 P07550 Q9NR21-5 false 3 P07550 Q8WVD3 false 3 P07550 Q9H0X6 false 3 P07550 Q13573 false 3 P07550 P12931 false 3 P07550 Q5T0J7-2 false 3 P07550 Q8N0U2 false 3 Cell membrane Multi-pass membrane protein Early endosome Golgi apparatus Colocalizes with VHL at the cell membrane (PubMed:19584355). Activated receptors are internalized into endosomes prior to their degradation in lysosomes (PubMed:20559325). Activated receptors are also detected within the Golgi apparatus (PubMed:27481942). Palmitoylated (PubMed:11146000, PubMed:17962520, PubMed:18547522, PubMed:2540197, PubMed:27481942). Mainly palmitoylated at Cys-341 (PubMed:17962520, PubMed:18547522, PubMed:2540197). Palmitoylation may reduce accessibility of phosphorylation sites by anchoring the receptor to the plasma membrane. Agonist stimulation promotes depalmitoylation and further allows Ser-345 and Ser-346 phosphorylation (PubMed:11146000). Also undergoes transient, ligand-induced palmitoylation at Cys-265 probably by ZDHHC9, ZDHHC14 and ZDHHC18 within the Golgi (PubMed:27481942). Palmitoylation at Cys-265 requires phosphorylation by PKA and receptor internalization and stabilizes the receptor (PubMed:27481942). Could be depalmitoylated by LYPLA1 at the plasma membrane (PubMed:27481942). Phosphorylated by PKA and BARK upon agonist stimulation, which mediates homologous desensitization of the receptor. PKA-mediated phosphorylation seems to facilitate phosphorylation by BARK. Phosphorylation of Tyr-141 is induced by insulin and leads to supersensitization of the receptor. Polyubiquitinated (PubMed:23166351). Agonist-induced ubiquitination leads to sort internalized receptors to the lysosomes for degradation (PubMed:19424180, PubMed:20559325, PubMed:23166351). 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. Hydroxylation by EGLN3 occurs only under normoxia and increases the interaction with VHL and the subsequent ubiquitination and degradation of ADRB2. 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. Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB2 sub-subfamily. Extended N-terminus. 3D-structure Cell membrane Disulfide bond Endosome G-protein coupled receptor Glycoprotein Golgi apparatus Hydroxylation Lipoprotein Membrane Palmitate Phosphoprotein Proteomics identification Receptor Reference proteome Transducer Transmembrane Transmembrane helix Ubl conjugation (S)-carazolol inverse agonist (S)-timolol inverse agonist (S)-timolol inverse agonist (S)-carazolol inverse agonist (S)-timolol inverse agonist (S)-carazolol inverse agonist (S)-timolol inverse agonist (S)-timolol inverse agonist N S G R E Q V M I F I L T I S C K R D N Y F C A C A C G SS AA Y A Y A Y F F L V A S P Q P MGQPGNGSAFLLAPNGSHAPDHDVTQERDEVWVVGMGIVMSLIVLAIVFGNVLVITAIAKFERLQTVTNYFITSLACADLVMGLAVVPFGAAHILMKMWTFGNFWCEFWTSIDVLCVTASIETLCVIAVDRYFAITSPFKYQSLLTKNKARVIILMVWIVSGLTSFLPIQMHWYRATHQEAINCYANETCCDFFTNQAYAIASSIVSFYVPLVIMVFVYSRVFQEAKRQLQKIDKSEGRFHVQNLSQVEQDGRTGHGLRRSSKFCLKEHKALKTLGIIMGTFTLCWLPFFIVNIVHVIQDNLIRKEVYILLNWIGYVNSGFNPLIYCRSPDFRIAFQELLCLRRSSLKAYGNGYSSNGNTGEQSGYHVEQEKENKLLCEDLPGTEDFVGHQGTVPSDNIDSQGRNCSTNDSLL Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms Distributed under the Creative Commons Attribution (CC BY 4.0) License