ADRB2
entrez
154
canonical
uniprot
P07550
canonical
ensembl
ENSG00000169252
resolver
ensp
ENSP00000305372
resolver
enst
ENST00000305988
resolver
genesymbol
ADRB2
resolver
genesymbol_syn
ADRB2R
resolver
genesymbol_syn
B2AR
resolver
hgnc
HGNC:286
resolver
uniprot
B0LPE4
resolver
uniprot
B2R7X2
resolver
uniprot
O14823
resolver
uniprot
O14824
resolver
uniprot
O14825
resolver
uniprot
O14826
resolver
uniprot
Q4JG18
resolver
uniprot
Q53GA6
resolver
uniprot
Q6GMT4
resolver
uniprot
Q6P4D8
resolver
uniprot
Q8NEQ9
resolver
uniprot
Q96EC3
resolver
uniprot
Q9UCZ0
resolver
uniprot
Q9UCZ1
resolver
uniprot
Q9UCZ2
resolver
uniprot
Q9UCZ3
resolver
uniprot
Q9UH95
resolver
uniprot
Q9UHA1
resolver
uniprot
Q9UMZ5
resolver
uniprot
X5DQM5
resolver
uniprot_entry
ADRB2_HUMAN
resolver
uniprot_entry
X5DQM5_HUMAN
resolver
uniprot_sec
B0LPE4
resolver
uniprot_sec
B2R7X2
resolver
uniprot_sec
O14823
resolver
uniprot_sec
O14824
resolver
uniprot_sec
O14825
resolver
uniprot_sec
O14826
resolver
uniprot_sec
Q4JG18
resolver
uniprot_sec
Q53GA6
resolver
uniprot_sec
Q6GMT4
resolver
uniprot_sec
Q6P4D8
resolver
uniprot_sec
Q8NEQ9
resolver
uniprot_sec
Q96EC3
resolver
uniprot_sec
Q9UCZ0
resolver
uniprot_sec
Q9UCZ1
resolver
uniprot_sec
Q9UCZ2
resolver
uniprot_sec
Q9UCZ3
resolver
uniprot_sec
Q9UH95
resolver
uniprot_sec
Q9UHA1
resolver
uniprot_sec
Q9UMZ5
resolver
amino_acid_sequence
MGQPGNGSAFLLAPNGSHAPDHDVTQERDEVWVVGMGIVMSLIVLAIVFGNVLVITAIAKFERLQTVTNYFITSLACADLVMGLAVVPFGAAHILMKMWTFGNFWCEFWTSIDVLCVTASIETLCVIAVDRYFAITSPFKYQSLLTKNKARVIILMVWIVSGLTSFLPIQMHWYRATHQEAINCYANETCCDFFTNQAYAIASSIVSFYVPLVIMVFVYSRVFQEAKRQLQKIDKSEGRFHVQNLSQVEQDGRTGHGLRRSSKFCLKEHKALKTLGIIMGTFTLCWLPFFIVNIVHVIQDNLIRKEVYILLNWIGYVNSGFNPLIYCRSPDFRIAFQELLCLRRSSLKAYGNGYSSNGNTGEQSGYHVEQEKENKLLCEDLPGTEDFVGHQGTVPSDNIDSQGRNCSTNDSLL
uniprot
proteins
function
FUNCTION: G protein-coupled receptor for catecholamines that couples to both G(s) and G(i) proteins, activating bifurcated signaling pathways (PubMed:2831218, PubMed:7915137). ADRB2 binds epinephrine (Epi) with an approximately 30-fold greater affinity than norepinephrine (NE) (PubMed:2831218, PubMed:33093660, PubMed:7915137). In the heart, Epi- and NE-activated ADRB2 induces rapid and slow cardiomyocyte contraction rate, respectively (By similarity). Both NE and Epi promote coupling to G(s)/PKA pathway to regulate myocyte contraction rate (By similarity). Epi also promotes ADRB2 coupling to G(i) proteins to exert cardioprotective effects especially in the conditions of hypoxia and oxidative stress through the G(i)/PI3K/Akt signaling pathway (By similarity). ADRB2-G(s) signaling delivers proapoptotic signals in cardiomyocytes although G(i)-mediated survival effect appears to predominate (By similarity). ADRB2 also transduces signals independently of PKA to regulate cellular pH by modulating Na(+)/H(+) exchanger SLC9A3 function (PubMed:9560162). {ECO:0000250|UniProtKB:P18762, ECO:0000269|PubMed:2831218, ECO:0000269|PubMed:33093660, ECO:0000269|PubMed:7915137, ECO:0000269|PubMed:9560162}.
uniprot
proteins
mass_dalton
46459
uniprot
proteins
mutagenesis
MUTAGEN 79; /note="D->N: Affects binding of catecholamines, and produces an uncoupling between the receptor and stimulatory G proteins."; /evidence="ECO:0000269|PubMed:2831218"; MUTAGEN 141; /note="Y->F: Abolishes insulin-induced tyrosine phosphorylation and insulin-induced receptor supersensitization."; /evidence="ECO:0000269|PubMed:8521811"; MUTAGEN 174; /note="Y->W: Increased noradrenaline affinity."; /evidence="ECO:0000269|PubMed:33093660"; MUTAGEN 265; /note="C->A: Loss of ligand-induced palmitoylation."; /evidence="ECO:0000269|PubMed:27481942"; MUTAGEN 300; /note="D->R: Increased noradrenaline affinity."; /evidence="ECO:0000269|PubMed:33093660"; MUTAGEN 341; /note="C->A: Loss of basal palmitoylation."; /evidence="ECO:0000269|PubMed:27481942"; MUTAGEN 341; /note="C->G: Uncoupled receptor."; /evidence="ECO:0000269|PubMed:2540197"; MUTAGEN 345..346; /note="SS->AA: Delayed agonist-promoted desensitization."; /evidence="ECO:0000269|PubMed:11146000"; MUTAGEN 350; /note="Y->A: Does not affect insulin-induced tyrosine phosphorylation or insulin-induced receptor supersensitization."; /evidence="ECO:0000269|PubMed:8521811"; MUTAGEN 354; /note="Y->A: Does not affect insulin-induced tyrosine phosphorylation or insulin-induced receptor supersensitization."; /evidence="ECO:0000269|PubMed:8521811"; MUTAGEN 366; /note="Y->F: Does not affect insulin-induced tyrosine phosphorylation or insulin-induced receptor supersensitization."; /evidence="ECO:0000269|PubMed:8521811"; MUTAGEN 413; /note="L->A: Loss of interaction with NHERF1 after isoprenaline stimulation. Inhibition of SLC9A3 activity after isoprenaline stimulation. No change in adenylyl cyclase activation."; /evidence="ECO:0000269|PubMed:9560162
uniprot
proteins
post_translational_modification
PTM: 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). {ECO:0000269|PubMed:11146000, ECO:0000269|PubMed:17962520, ECO:0000269|PubMed:18547522, ECO:0000269|PubMed:2540197, ECO:0000269|PubMed:27481942}.; PTM: Phosphorylated by PKA and BARK/GRK2 upon agonist stimulation, which mediates homologous desensitization of the receptor. PKA-mediated phosphorylation seems to facilitate phosphorylation by BARK/GRK2 (PubMed:11146000). Distinct temporal phosphorylation on Ser-355 and Ser-356 by BARK/GRK2 plays a critical role for dictating receptor cellular events and signaling properties induced by Epi or NE in cardiomyocytes (By similarity). {ECO:0000250|UniProtKB:P18762, ECO:0000269|PubMed:11146000}.; PTM: Phosphorylation of Tyr-141 is induced by insulin and leads to supersensitization of the receptor. {ECO:0000269|PubMed:8521811}.; PTM: 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. {ECO:0000269|PubMed:19424180, ECO:0000269|PubMed:20559325, ECO:0000269|PubMed:23166351}.; PTM: Hydroxylation 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}.
uniprot
proteins
protein_family
ADRB2 sub-subfamily
uniprot
proteins
protein_family
Adrenergic receptor subfamily
uniprot
proteins
protein_family
G protein-coupled receptor 1 family
uniprot
proteins
pubmed
10499588
uniprot
proteins
pubmed
11146000
uniprot
proteins
pubmed
11246467
uniprot
proteins
pubmed
12142540
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17525332
uniprot
proteins
pubmed
17952055
uniprot
proteins
pubmed
17962520
uniprot
proteins
pubmed
18056263
uniprot
proteins
pubmed
18547522
uniprot
proteins
pubmed
19424180
uniprot
proteins
pubmed
19584355
uniprot
proteins
pubmed
20559325
uniprot
proteins
pubmed
20733053
uniprot
proteins
pubmed
21602791
uniprot
proteins
pubmed
23166351
uniprot
proteins
pubmed
24056936
uniprot
proteins
pubmed
24405750
uniprot
proteins
pubmed
25220262
uniprot
proteins
pubmed
2540197
uniprot
proteins
pubmed
27481942
uniprot
proteins
pubmed
2823249
uniprot
proteins
pubmed
2831218
uniprot
proteins
pubmed
3025863
uniprot
proteins
pubmed
3026848
uniprot
proteins
pubmed
3033609
uniprot
proteins
pubmed
3034889
uniprot
proteins
pubmed
33093660
uniprot
proteins
pubmed
7706471
uniprot
proteins
pubmed
7822302
uniprot
proteins
pubmed
7915137
uniprot
proteins
pubmed
8383511
uniprot
proteins
pubmed
8521811
uniprot
proteins
pubmed
9388255
uniprot
proteins
pubmed
9560162
uniprot
proteins
pubmed
9924018
uniprot
proteins
sequence_length
413
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19584355, ECO:0000269|PubMed:20559325, ECO:0000269|PubMed:23166351, ECO:0000269|PubMed:25220262, ECO:0000269|PubMed:2831218, ECO:0000269|PubMed:7915137}; Multi-pass membrane protein {ECO:0000269|PubMed:19584355, ECO:0000269|PubMed:24056936}. Golgi apparatus {ECO:0000269|PubMed:27481942}. Note=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). {ECO:0000269|PubMed:19584355, ECO:0000269|PubMed:20559325, ECO:0000269|PubMed:27481942}.
uniprot
proteins
transmembrane_region
TRANSMEM 30..56; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:24056936, ECO:0007744|PDB:4LDE"; TRANSMEM 71..96; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:24056936, ECO:0007744|PDB:4LDE"; TRANSMEM 104..129; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:24056936, ECO:0007744|PDB:4LDE"; TRANSMEM 150..171; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:24056936, ECO:0007744|PDB:4LDE"; TRANSMEM 198..220; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:24056936, ECO:0007744|PDB:4LDE"; TRANSMEM 275..298; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:24056936, ECO:0007744|PDB:4LDE"; TRANSMEM 305..326; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:24056936, ECO:0007744|PDB:4LDE
uniprot
proteins