Beta-2 adrenergic receptor

Details

Name
Beta-2 adrenergic receptor
Synonyms
  • ADRB2R
  • B2AR
  • Beta-2 adrenoceptor
  • Beta-2 adrenoreceptor
Gene Name
ADRB2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0037061|Beta-2 adrenergic receptor
MGQPGNGSAFLLAPNGSHAPDHDVTQERDEVWVVGMGIVMSLIVLAIVFGNVLVITAIAK
FERLQTVTNYFITSLACADLVMGLAVVPFGAAHILMKMWTFGNFWCEFWTSIDVLCVTAS
IETLCVIAVDRYFAITSPFKYQSLLTKNKARVIILMVWIVSGLTSFLPIQMHWYRATHQE
AINCYANETCCDFFTNQAYAIASSIVSFYVPLVIMVFVYSRVFQEAKRQLQKIDKSEGRF
HVQNLSQVEQDGRTGHGLRRSSKFCLKEHKALKTLGIIMGTFTLCWLPFFIVNIVHVIQD
NLIRKEVYILLNWIGYVNSGFNPLIYCRSPDFRIAFQELLCLRRSSLKAYGNGYSSNGNT
GEQSGYHVEQEKENKLLCEDLPGTEDFVGHQGTVPSDNIDSQGRNCSTNDSLL
Number of residues
413
Molecular Weight
46458.32
Theoretical pI
7.44
GO Classification
Functions
beta2-adrenergic receptor activity / dopamine binding / drug binding / epinephrine binding / norepinephrine binding / potassium channel regulator activity / protein homodimerization activity
Processes
activation of adenylate cyclase activity / activation of transmembrane receptor protein tyrosine kinase activity / adenylate cyclase-activating adrenergic receptor signaling pathway / adenylate cyclase-modulating G-protein coupled receptor signaling pathway / aging / associative learning / bone resorption / brown fat cell differentiation / cell surface receptor signaling pathway / cell-cell signaling / cellular response to hypoxia / desensitization of G-protein coupled receptor protein signaling pathway by arrestin / diaphragm contraction / diet induced thermogenesis / endosome to lysosome transport / estrous cycle / excitatory postsynaptic potential / female pregnancy / heat generation / liver regeneration / mitophagy in response to mitochondrial depolarization / negative regulation of angiogenesis / negative regulation of inflammatory response / negative regulation of multicellular organism growth / negative regulation of ossification / negative regulation of platelet aggregation / negative regulation of smooth muscle contraction / negative regulation of urine volume / positive regulation of apoptotic process / positive regulation of ATPase activity / positive regulation of autophagosome maturation / positive regulation of bone mineralization / positive regulation of cell proliferation / positive regulation of lipophagy / positive regulation of MAPK cascade / positive regulation of potassium ion transport / positive regulation of protein ubiquitination / positive regulation of skeletal muscle tissue growth / positive regulation of sodium ion transport / positive regulation of the force of heart contraction by epinephrine / positive regulation of transcription from RNA polymerase II promoter / positive regulation of vasodilation / receptor-mediated endocytosis / regulation of calcium ion transport / regulation of sensory perception of pain / response to cold / response to dexamethasone / response to estrogen / response to monoamine / response to progesterone / response to testosterone / synaptic transmission, glutamatergic / vasodilation by norepinephrine-epinephrine involved in regulation of systemic arterial blood pressure / wound healing
Components
apical plasma membrane / axon / dendritic spine / early endosome / endosome / integral component of plasma membrane / lysosome / neuronal cell body membrane / nucleus / plasma membrane / receptor complex / sarcolemma
General Function
Protein homodimerization activity
Specific Function
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.
Pfam Domain Function
Transmembrane Regions
35-58 72-95 107-129 151-174 197-220 275-298 306-329
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0020478|Beta-2 adrenergic receptor (ADRB2)
ATGGGGCAACCCGGGAACGGCAGCGCCTTCTTGCTGGCACCCAATAGAAGCCATGCGCCG
GACCACGACGTCACGCAGCAAAGGGACGAGGTGTGGGTGGTGGGCATGGGCATCGTCATG
TCTCTCATCGTCCTGGCCATCGTGTTTGGCAATGTGCTGGTCATCACAGCCATTGCCAAG
TTCGAGCGTCTGCAGACGGTCACCAACTACTTCATCACTTCACTGGCCTGTGCTGATCTG
GTCATGGGCCTGGCAGTGGTGCCCTTTGGGGCCGCCCATATTCTTATGAAAATGTGGACT
TTTGGCAACTTCTGGTGCGAGTTTTGGACTTCCATTGATGTGCTGTGCGTCACGGCCAGC
ATTGAGACCCTGTGCGTGATCGCAGTGGATCGCTACTTTGCCATTACTTCACCTTTCAAG
TACCAGAGCCTGCTGACCAAGAATAAGGCCCGGGTGATCATTCTGATGGTGTGGATTGTG
TCAGGCCTTACCTCCTTCTTGCCCATTCAGATGCACTGGTACCGGGCCACCCACCAGGAA
GCCATCAACTGCTATGCCAATGAGACCTGCTGTGACTTCTTCACGAACCAAGCCTATGCC
ATTGCCTCTTCCATCGTGTCCTTCTACGTTCCCCTGGTGATCATGGTCTTCGTCTACTCC
AGGGTCTTTCAGGAGGCCAAAAGGCAGCTCCAGAAGATTGACAAATCTGAGGGCCGCTTC
CATGTCCAGAACCTTAGCCAGGTGGAGCAGGATGGGCGGACGGGGCATGGACTCCGCAGA
TCTTCCAAGTTCTGCTTGAAGGAGCACAAAGCCCTCAAGACGTTAGGCATCATCATGGGC
ACTTTCACCCTCTGCTGGCTGCCCTTCTTCATCGTTAACATTGTGCATGTGATCCAGGAT
AACCTCATCCGTAAGGAAGTTTACATCCTCCTAAATTGGATAGGCTATGTCAATTCTGGT
TTCAATCCCCTTATCTACTGCCGGAGCCCAGATTTCAGGATTGCCTTCCAGGAGCTTCTG
TGCCTGCGCAGGTCTTCTTTGAAGGCCTATGGGAATGGCTACTCCAGCAACGGCAACACA
GGGGAGCAGAGTGGATATCACGTGGAACAGGAGAAAGAAAATAAACTGCTGTGTGAAGAC
CTCCCAGGCACGGAAGACTTTGTGGGCCATCAAGGTACTGTGCCTAGCGATAACATTGAT
TCACAAGGGAGGAATTGTAGTACAAATGACTCACTGCTGTAA
Chromosome Location
5
Locus
5q31-q32
External Identifiers
ResourceLink
UniProtKB IDP07550
UniProtKB Entry NameADRB2_HUMAN
GenBank Protein ID29371
GenBank Gene IDY00106
GenAtlas IDADRB2
HGNC IDHGNC:286
General References
  1. Chung FZ, Lentes KU, Gocayne J, Fitzgerald M, Robinson D, Kerlavage AR, Fraser CM, Venter JC: Cloning and sequence analysis of the human brain beta-adrenergic receptor. Evolutionary relationship to rodent and avian beta-receptors and porcine muscarinic receptors. FEBS Lett. 1987 Jan 26;211(2):200-6. [PubMed:3026848]
  2. Kobilka BK, Frielle T, Dohlman HG, Bolanowski MA, Dixon RA, Keller P, Caron MG, Lefkowitz RJ: Delineation of the intronless nature of the genes for the human and hamster beta 2-adrenergic receptor and their putative promoter regions. J Biol Chem. 1987 May 25;262(15):7321-7. [PubMed:3034889]
  3. Schofield PR, Rhee LM, Peralta EG: Primary structure of the human beta-adrenergic receptor gene. Nucleic Acids Res. 1987 Apr 24;15(8):3636. [PubMed:3033609]
  4. Kobilka BK, Dixon RA, Frielle T, Dohlman HG, Bolanowski MA, Sigal IS, Yang-Feng TL, Francke U, Caron MG, Lefkowitz RJ: 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. Proc Natl Acad Sci U S A. 1987 Jan;84(1):46-50. [PubMed:3025863]
  5. Emorine LJ, Marullo S, Delavier-Klutchko C, Kaveri SV, Durieu-Trautmann O, Strosberg AD: Structure of the gene for human beta 2-adrenergic receptor: expression and promoter characterization. Proc Natl Acad Sci U S A. 1987 Oct;84(20):6995-9. [PubMed:2823249]
  6. Reihsaus E, Innis M, MacIntyre N, Liggett SB: Mutations in the gene encoding for the beta 2-adrenergic receptor in normal and asthmatic subjects. Am J Respir Cell Mol Biol. 1993 Mar;8(3):334-9. [PubMed:8383511]
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  10. Chung FZ, Wang CD, Potter PC, Venter JC, Fraser CM: Site-directed mutagenesis and continuous expression of human beta-adrenergic receptors. Identification of a conserved aspartate residue involved in agonist binding and receptor activation. J Biol Chem. 1988 Mar 25;263(9):4052-5. [PubMed:2831218]
  11. O'Dowd BF, Hnatowich M, Caron MG, Lefkowitz RJ, Bouvier M: Palmitoylation of the human beta 2-adrenergic receptor. Mutation of Cys341 in the carboxyl tail leads to an uncoupled nonpalmitoylated form of the receptor. J Biol Chem. 1989 May 5;264(13):7564-9. [PubMed:2540197]
  12. Valiquette M, Parent S, Loisel TP, Bouvier M: Mutation of tyrosine-141 inhibits insulin-promoted tyrosine phosphorylation and increased responsiveness of the human beta 2-adrenergic receptor. EMBO J. 1995 Nov 15;14(22):5542-9. [PubMed:8521811]
  13. Gurevich VV, Dion SB, Onorato JJ, Ptasienski J, Kim CM, Sterne-Marr R, Hosey MM, Benovic JL: 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. J Biol Chem. 1995 Jan 13;270(2):720-31. [PubMed:7822302]
  14. Lin FT, Krueger KM, Kendall HE, Daaka Y, Fredericks ZL, Pitcher JA, Lefkowitz RJ: Clathrin-mediated endocytosis of the beta-adrenergic receptor is regulated by phosphorylation/dephosphorylation of beta-arrestin1. J Biol Chem. 1997 Dec 5;272(49):31051-7. [PubMed:9388255]
  15. Cao TT, Deacon HW, Reczek D, Bretscher A, von Zastrow M: A kinase-regulated PDZ-domain interaction controls endocytic sorting of the beta2-adrenergic receptor. Nature. 1999 Sep 16;401(6750):286-90. [PubMed:10499588]
  16. Luttrell LM, Ferguson SS, Daaka Y, Miller WE, Maudsley S, Della Rocca GJ, Lin F, Kawakatsu H, Owada K, Luttrell DK, Caron MG, Lefkowitz RJ: Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes. Science. 1999 Jan 29;283(5402):655-61. [PubMed:9924018]
  17. Moffett S, Rousseau G, Lagace M, Bouvier M: 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. J Neurochem. 2001 Jan;76(1):269-79. [PubMed:11146000]
  18. Whistler JL, Enquist J, Marley A, Fong J, Gladher F, Tsuruda P, Murray SR, Von Zastrow M: Modulation of postendocytic sorting of G protein-coupled receptors. Science. 2002 Jul 26;297(5581):615-20. [PubMed:12142540]
  19. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007 May 25;316(5828):1160-6. [PubMed:17525332]
  20. Berthouze M, Venkataramanan V, Li Y, Shenoy SK: The deubiquitinases USP33 and USP20 coordinate beta2 adrenergic receptor recycling and resensitization. EMBO J. 2009 Jun 17;28(12):1684-96. doi: 10.1038/emboj.2009.128. Epub 2009 May 7. [PubMed:19424180]
  21. Xie L, Xiao K, Whalen EJ, Forrester MT, Freeman RS, Fong G, Gygi SP, Lefkowitz RJ, Stamler JS: Oxygen-regulated beta(2)-adrenergic receptor hydroxylation by EGLN3 and ubiquitylation by pVHL. Sci Signal. 2009 Jul 7;2(78):ra33. doi: 10.1126/scisignal.2000444. [PubMed:19584355]
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  28. Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Kuhn P, Weis WI, Kobilka BK, Stevens RC: High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science. 2007 Nov 23;318(5854):1258-65. Epub 2007 Oct 25. [PubMed:17962520]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00521CarteololapprovedyesantagonistDetails
DB00816OrciprenalineapprovedyesagonistDetails
DB00867Ritodrineapproved, investigationalyesagonistDetails
DB00871TerbutalineapprovedyesagonistDetails
DB00901BitolterolwithdrawnyesDetails
DB00938SalmeterolapprovedyesagonistDetails
DB00983Formoterolapproved, investigationalyesagonistDetails
DB01001Salbutamolapproved, vet_approvedyesagonistDetails
DB00373TimololapprovedyesantagonistDetails
DB00571Propranololapproved, investigationalunknownantagonistDetails
DB00598LabetalolapprovedyesantagonistDetails
DB00612BisoprololapprovednoantagonistDetails
DB00668Epinephrineapproved, vet_approvedyesagonistDetails
DB00852Pseudoephedrineapprovedunknownpartial agonistDetails
DB00866Alprenololexperimental, withdrawnyesantagonistDetails
DB00960Pindololapproved, investigationalyespartial agonistDetails
DB01064Isoprenalineapproved, investigationalyesagonistDetails
DB01151Desipramineapproved, investigationalunknownantagonistDetails
DB01203NadololapprovedunknownantagonistDetails
DB01210LevobunololapprovedyesantagonistDetails
DB01214MetipranololapprovedyesantagonistDetails
DB01274Arformoterolapproved, investigationalyesagonistDetails
DB01366Procaterolapproved, investigationalyesagonistDetails
DB01407Clenbuterolapproved, investigational, vet_approvedyesagonistDetails
DB01136Carvedilolapproved, investigationalunknownantagonistDetails
DB01288Fenoterolapproved, investigationalyesagonistDetails
DB01291PirbuterolapprovedyesagonistDetails
DB01580OxprenololapprovedunknownantagonistDetails
DB01359Penbutololapproved, investigationalyesantagonistpartial agonistDetails
DB00368NorepinephrineapprovedyesagonistDetails
DB01408BambuterolinvestigationalyesagonistDetails
DB05039IndacaterolapprovedyesagonistDetails
DB05849NCX 950investigationalunknownDetails
DB06262Droxidopaapproved, investigationalyesagonistDetails
DB00264Metoprololapproved, investigationalunknownantagonistDetails
DB00195Betaxololapproved, investigationalunknownantagonistDetails
DB00489SotalolapprovedyesantagonistDetails
DB01295BevantololexperimentalunknownantagonistDetails
DB01193Acebutololapproved, investigationalunknownpartial agonistDetails
DB01102ArbutamineapprovedunknownagonistDetails
DB00841DobutamineapprovedunknownagonistDetails
DB07543(2S)-1-(9H-Carbazol-4-yloxy)-3-(isopropylamino)propan-2-olexperimentalunknownDetails
DB00449DipivefrinapprovedyesagonistDetails
DB08807Bopindololexperimentalunknownpartial agonistDetails
DB08808BupranololexperimentalunknownantagonistDetails
DB04861Nebivololapproved, investigationalunknownantagonistDetails
DB00925PhenoxybenzamineapprovedunknownDetails
DB01363Ephedraapproved, nutraceutical, withdrawnyesagonistDetails
DB06216AsenapineapprovedunknownantagonistDetails
DB00370MirtazapineapprovedunknownbinderDetails
DB00248CabergolineapprovedunknownbinderDetails
DB00221IsoetarineapprovedunknownagonistDetails
DB00335AtenololapprovedunknowninhibitorDetails
DB00397Phenylpropanolamineapproved, vet_approved, withdrawnunknownagonistDetails
DB09080OlodaterolapprovedyesagonistDetails
DB09082VilanterolapprovedyesagonistDetails
DB04846Celiprololapproved, investigationalyesagonistDetails
DB13139Levosalbutamolapproved, investigationalyesagonistDetails
DB09013BefunololexperimentalunknownDetails
DB12248TulobuterolinvestigationalunknownDetails
DB01917PutrescineexperimentalunknownDetails
DB03566SpermidineexperimentalunknownDetails
DB00127Spermineexperimental, nutraceuticalunknownDetails
DB01182PropafenoneapprovedunknownantagonistDetails
DB09204ArotinololinvestigationalyesantagonistDetails
DB09273DoxofyllineexperimentalyesagonistDetails
DB06814Protokylolapproved, vet_approvedyesagonistDetails
DB11124RacepinephrineapprovedyesagonistDetails
DB11587EtafedrineapprovedyesagonistDetails