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Details on Person UniProt:P07550 ADRB2
| Class:Id | ReferenceGeneProduct:50589 |
|---|---|
| _chainChangeLog | chain:1-413 added on Sat February 7 2015 |
| _displayName | UniProt:P07550 ADRB2 |
| _timestamp | 2026-02-20 23:02:48 |
| chain | chain:1-413 |
| checksum | 408C22731C6EDFBE |
| comment | 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).SUBUNIT Binds NHERF1 and GPRASP1 (PubMed:9560162). 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).INTERACTION 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).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).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).PTM Phosphorylation of Tyr-141 is induced by insulin and leads to supersensitization of the receptor.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.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 Extended N-terminus. |
| description | recommendedName: fullName evidence="44"Beta-2 adrenergic receptor alternativeName: Beta-2 adrenoreceptor shortName: Beta-2 adrenoceptor |
| geneName | ADRB2 ADRB2R B2AR |
| identifier | P07550 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Cell membrane Disulfide bond G-protein coupled receptor Glycoprotein Golgi apparatus Hydroxylation Lipoprotein Membrane Palmitate Phosphoprotein Proteomics identification Receptor Reference proteome Transducer Transmembrane Transmembrane helix Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | ADRB2 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8999895] ENSEMBL:ENSG00000169252 ADRB2 [Homo sapiens] |
| secondaryIdentifier | ADRB2_HUMAN B0LPE4 B2R7X2 O14823 O14824 O14825 O14826 Q4JG18 Q53GA6 Q6GMT4 Q6P4D8 Q8NEQ9 Q96EC3 Q9UCZ0 Q9UCZ1 Q9UCZ2 Q9UCZ3 Q9UH95 Q9UHA1 Q9UMZ5 |
| sequenceLength | 413 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:390647] ADRB2 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:6783036] ADRB2 [endosome membrane] [Homo sapiens] [EntityWithAccessionedSequence:6783066] PolyUb-ADRB2 [endosome membrane] [Homo sapiens] [EntityWithAccessionedSequence:8852158] pS-ADRB2 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:8869143] pS-ADRB2 [clathrin-coated endocytic vesicle membrane] [Homo sapiens] |
| (referenceSequence) | [GroupModifiedResidue:6783062] ubiquitinylated lysine (PolyUb [cytosol]) at unknown position [ModifiedResidue:8852160] O-phospho-L-serine at unknown position |
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No pathways have been reviewed or authored by UniProt:P07550 ADRB2 (50589)
