Beta-2 adrenergic receptor
Also known as: ADRB2, ADRB2R, B2AR
Function
G protein-coupled receptor for catecholamines that couples to both G(s) and G(i) proteins, activating bifurcated signaling pathways. ADRB2 binds epinephrine (Epi) with an approximately 30-fold greater affinity than norepinephrine (NE). 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.
Classification
- Family (Pfam)
- PF00001 7tm_1
- InterPro
- ADR_fam, ADRB2_rcpt, GPCR_Rhodpsn, GPCR_Rhodpsn_7TM
- Functional cluster
- G Protein-Coupled Receptors
Experimental structures · PDB · 139
- 1GQ4 X-ray 1.90A
- 2R4R X-ray 3.40A
- 2R4S X-ray 3.40A
- 2RH1 X-ray 2.40A
- 3D4S X-ray 2.80A
- 3KJ6 X-ray 3.40A
- 3NY8 X-ray 2.84A
- 3NY9 X-ray 2.84A
- 3NYA X-ray 3.16A
- 3P0G X-ray 3.50A
- 3PDS X-ray 3.50A
- 3SN6 X-ray 3.20A
- … and 127 more
A predicted model is available from AlphaFold.
Gene Ontology · 41
- GO:0016324 apical plasma membrane
- GO:0030669 clathrin-coated endocytic vesicle membrane
- GO:0005768 endosome
- GO:0010008 endosome membrane
- GO:0005794 Golgi apparatus
- GO:0005764 lysosome
- GO:0016020 membrane
- GO:0098992 neuronal dense core vesicle
- GO:0005634 nucleus
- GO:0005886 plasma membrane
- GO:0043235 receptor complex
- GO:0008179 adenylate cyclase binding
- GO:0001540 amyloid-beta binding
- GO:0004941 beta2-adrenergic receptor activity
- GO:0042802 identical protein binding
- GO:0051380 norepinephrine binding
- GO:0015459 potassium channel regulator activity
- GO:0042803 protein homodimerization activity
- GO:0044877 protein-containing complex binding
- GO:0071880 adenylate cyclase-activating adrenergic receptor signaling pathway
- GO:0071881 adenylate cyclase-inhibiting adrenergic receptor signaling pathway
- GO:0007188 adenylate cyclase-modulating G protein-coupled receptor signaling pathway
- GO:0071875 adrenergic receptor signaling pathway
- GO:0098990 AMPA selective glutamate receptor signaling pathway
- GO:0007166 cell surface receptor signaling pathway
- GO:1904646 cellular response to amyloid-beta
- GO:0008333 endosome to lysosome transport
- GO:0010667 negative regulation of cardiac muscle cell apoptotic process
- GO:0045744 negative regulation of G protein-coupled receptor signaling pathway
- GO:0002025 norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure
- GO:1901098 positive regulation of autophagosome maturation
- GO:0010666 positive regulation of cardiac muscle cell apoptotic process
- GO:0106134 positive regulation of cardiac muscle cell contraction
- GO:0120162 positive regulation of cold-induced thermogenesis
- GO:1900451 positive regulation of glutamate receptor signaling pathway
- GO:1904504 positive regulation of lipophagy
- GO:0043410 positive regulation of MAPK cascade
- GO:0061885 positive regulation of mini excitatory postsynaptic potential
- GO:0006898 receptor-mediated endocytosis
- GO:0006940 regulation of smooth muscle contraction
- GO:1990911 response to psychosocial stress
Disease associations
- OMIM:109690 RAW:OMIM_109690
Drugs targeting this protein · 70
- SALMETEROL XINAFOATE agonist
- VILANTEROL TRIFENATATE agonist
- VILANTEROL .ALPHA.-PHENYL CINNAMATE agonist
- CARMOTEROL agonist
- REPROTEROL agonist
- TULOBUTEROL agonist
- LABETALOL HYDROCHLORIDE antagonist
- BITOLTEROL MESYLATE agonist
- DOBUTAMINE HYDROCHLORIDE agonist
- PIRBUTEROL ACETATE agonist
- HYDROXYAMPHETAMINE HYDROBROMIDE agonist
- OXPRENOLOL HYDROCHLORIDE antagonist
- DIPIVEFRIN HYDROCHLORIDE agonist
- TIMOLOL MALEATE antagonist
- PROTOKYLOL HYDROCHLORIDE agonist
- ISOETHARINE HYDROCHLORIDE agonist
- METIPRANOLOL HYDROCHLORIDE antagonist
- CARTEOLOL HYDROCHLORIDE antagonist
- LEVALBUTEROL HYDROCHLORIDE agonist
- PROPAFENONE HYDROCHLORIDE antagonist
- ESMOLOL HYDROCHLORIDE antagonist
- ISOETHARINE MESYLATE agonist
- CARVEDILOL PHOSPHATE antagonist
- LEVOBUNOLOL HYDROCHLORIDE antagonist
- NEBIVOLOL HYDROCHLORIDE antagonist
- DILEVALOL HYDROCHLORIDE antagonist
- PF-00610355 agonist
- EPINEPHRINE BITARTRATE agonist
- TERBUTALINE SULFATE agonist
- RITODRINE HYDROCHLORIDE agonist
- NOREPINEPHRINE BITARTRATE agonist
- ALBUTEROL SULFATE agonist
- EPHEDRINE SULFATE agonist
- METAPROTERENOL SULFATE agonist
- PROCATEROL agonist
- PRONETALOL antagonist
- PROPRANOLOL HYDROCHLORIDE antagonist
- SOTALOL HYDROCHLORIDE antagonist
- ISOPROTERENOL HYDROCHLORIDE agonist
- INDACATEROL MALEATE agonist
- MILVETEROL agonist
- ARFORMOTEROL TARTRATE agonist
- LY377604 antagonist
- DROXIDOPA agonist
- OLODATEROL HYDROCHLORIDE agonist
- BUCINDOLOL HYDROCHLORIDE antagonist
- EPHEDRINE HYDROCHLORIDE agonist
- BEDORADRINE SULFATE agonist
- PENBUTOLOL SULFATE antagonist
- CELIPROLOL partial agonist
- BATEFENTEROL agonist
- ABEDITEROL agonist
- MEPHENTERMINE SULFATE agonist
- BUCINDOLOL antagonist
- FENOTEROL agonist
- LAS190792 agonist
- ISOPROTERENOL SULFATE agonist
- LEVALBUTEROL TARTRATE agonist
- FORMOTEROL FUMARATE agonist
- NAVAFENTEROL agonist
- CLENBUTEROL agonist
- TIMOLOL antagonist
- PINDOLOL partial agonist
- BAMBUTEROL agonist
- NADOLOL antagonist
- ISOXSUPRINE HYDROCHLORIDE agonist
- EPINEPHRINE agonist
- ALBUTEROL agonist
- CARVEDILOL antagonist
- RIMITEROL agonist
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- Beta-2 adrenergic receptor 1.00
- Beta-2 adrenergic receptor 0.99
- Beta-2 adrenergic receptor 0.99
- Beta-2 adrenergic receptor 0.99
- Beta-2 adrenergic receptor 0.99
- Beta-2 adrenergic receptor 0.99
- Beta-2 adrenergic receptor 0.99
- Beta-2 adrenergic receptor 0.99
- Beta-2 adrenergic receptor 0.99
- Beta-2 adrenergic receptor 0.97
- Beta-1 adrenergic receptor 0.95
- Beta-2 adrenergic receptor 0.94
Co-cited proteins · studied together in the literature
- Arrestin domain-containing protein 3 2 shared papers
- Sorting nexin-27 2 shared papers
- Beta-1 adrenergic receptor 1 shared papers
- Beta-2 adrenergic receptor 1 shared papers
- Na(+)/H(+) exchange regulatory cofactor NHE-RF1 1 shared papers
- Beta-arrestin-1 2 shared papers
- Ubiquitin carboxyl-terminal hydrolase 33 2 shared papers
- Protein cornichon homolog 4 1 shared papers
- Delta-type opioid receptor 1 shared papers
- G protein-coupled receptor kinase 2 1 shared papers
- Ubiquitin carboxyl-terminal hydrolase 20 2 shared papers
- Na(+)/H(+) exchange regulatory cofactor NHE-RF1 1 shared papers
Literature · 37 cited papers
- Binding pathway determines norepinephrine selectivity for the human beta1AR over beta2AR. Cell Res. · 2021
- S-Palmitoylation of a Novel Site in the beta2-Adrenergic Receptor Associated with a Novel Intracellular Itinerary. J. Biol. Chem. · 2016
- Insights into beta2-adrenergic receptor binding from structures of the N-terminal lobe of ARRDC3. Protein Sci. · 2014
- CNIH4 interacts with newly synthesized GPCR and controls their export from the endoplasmic reticulum. Traffic · 2014
- Adrenaline-activated structure of beta2-adrenoceptor stabilized by an engineered nanobody. Nature · 2013
- MARCH2 promotes endocytosis and lysosomal sorting of carvedilol-bound beta(2)-adrenergic receptors. J. Cell Biol. · 2012
- SNX27 mediates retromer tubule entry and endosome-to-plasma membrane trafficking of signalling receptors. Nat. Cell Biol. · 2011
- SNX27 mediates PDZ-directed sorting from endosomes to the plasma membrane. J. Cell Biol. · 2010
- Arrestin domain-containing protein 3 recruits the NEDD4 E3 ligase to mediate ubiquitination of the beta2-adrenergic receptor. EMBO Rep. · 2010
- Oxygen-regulated beta(2)-adrenergic receptor hydroxylation by EGLN3 and ubiquitylation by pVHL. Sci. Signal. · 2009
- The deubiquitinases USP33 and USP20 coordinate beta2 adrenergic receptor recycling and resensitization. EMBO J. · 2009
- A specific cholesterol binding site is established by the 2.8 A structure of the human beta2-adrenergic receptor. Structure · 2008
- … and 25 more in the literature graph