Beta-2 adrenergic receptor

Details

Name
Beta-2 adrenergic receptor
Synonyms
  • ADRB2R
  • B2AR
  • Beta-2 adrenoceptor
  • Beta-2 adrenoreceptor
Gene Name
ADRB2
UniProtKB Entry
P07550Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
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 / norepinephrine binding / potassium channel regulator activity / protein homodimerization activity
Processes
activation of transmembrane receptor protein tyrosine kinase activity / adenylate cyclase-activating adrenergic receptor signaling pathway / bone resorption / brown fat cell differentiation / cell surface receptor signaling pathway / diet induced thermogenesis / endosome to lysosome transport / heat generation / negative regulation of multicellular organism growth / negative regulation of smooth muscle contraction / positive regulation of autophagosome maturation / positive regulation of bone mineralization / positive regulation of lipophagy / positive regulation of MAPK cascade / receptor-mediated endocytosis / response to cold
Components
apical plasma membrane / early endosome / endosome / lysosome / nucleus / plasma membrane / receptor complex
General 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
Specific Function
adenylate cyclase binding
Pfam Domain Function
Signal Regions
Not Available
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
5q32
External Identifiers
ResourceLink
UniProtKB IDP07550
UniProtKB Entry NameADRB2_HUMAN
GenBank Protein ID29371
GenBank Gene IDY00106
GeneCard IDADRB2
GenAtlas IDADRB2
HGNC IDHGNC:286
PDB ID(s)1GQ4, 2R4R, 2R4S, 2RH1, 3D4S, 3KJ6, 3NY8, 3NY9, 3NYA, 3P0G, 3PDS, 3SN6, 4GBR, 4LDE, 4LDL, 4LDO, 4QKX, 5D5A, 5D5B, 5D6L, 5JQH, 5X7D, 6E67, 6KR8, 6MXT, 6N48, 6NI3, 6OBA, 6PRZ, 6PS0, 6PS1, 6PS2, 6PS3, 6PS4, 6PS5, 6PS6, 7BZ2, 7DHI, 7DHR, 7XK9, 7XKA, 8GDZ, 8GE1, 8GE2, 8GE3, 8GE4, 8GE5, 8GE6, 8GE7, 8GE8, 8GE9, 8GEA, 8GEB, 8GEC, 8GED, 8GEE, 8GEF, 8GEG, 8GEH, 8GEI, 8GEJ, 8GFV, 8GFW, 8GFX, 8GFY, 8GFZ, 8GG0, 8GG1, 8GG2, 8GG3, 8GG4, 8GG5, 8GG6, 8GG7, 8GG8, 8GG9, 8GGA, 8GGB, 8GGC, 8GGE, 8GGF, 8GGI, 8GGJ, 8GGK, 8GGL, 8GGM, 8GGN, 8GGO, 8GGP, 8GGQ, 8GGR, 8GGS, 8GGT, 8GGU, 8GGV, 8GGW, 8GGX, 8GGY, 8GGZ, 8GH0, 8GH1, 8JJ8, 8JJL, 8JJO, 8UHB, 8UNL, 8UNM, 8UNN, 8UNO, 8UNP, 8UNQ, 8UNR, 8UNS, 8UNT, 8UNU, 8UNV, 8UNW, 8UNX, 8UNY, 8UNZ, 8UO0, 8UO1, 8UO2, 8UO3, 8UO4
KEGG IDhsa:154
IUPHAR/Guide To Pharmacology ID29
NCBI Gene ID154
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
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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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  22. Nabhan JF, Pan H, Lu Q: Arrestin domain-containing protein 3 recruits the NEDD4 E3 ligase to mediate ubiquitination of the beta2-adrenergic receptor. EMBO Rep. 2010 Aug;11(8):605-11. doi: 10.1038/embor.2010.80. Epub 2010 Jun 18. [Article]
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  24. Temkin P, Lauffer B, Jager S, Cimermancic P, Krogan NJ, von Zastrow M: SNX27 mediates retromer tubule entry and endosome-to-plasma membrane trafficking of signalling receptors. Nat Cell Biol. 2011 Jun;13(6):715-21. doi: 10.1038/ncb2252. Epub 2011 May 22. [Article]
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  29. Hanson MA, Cherezov V, Griffith MT, Roth CB, Jaakola VP, Chien EY, Velasquez J, Kuhn P, Stevens RC: A specific cholesterol binding site is established by the 2.8 A structure of the human beta2-adrenergic receptor. Structure. 2008 Jun;16(6):897-905. doi: 10.1016/j.str.2008.05.001. [Article]
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Associated Data

Bio-Entities
Bio-EntityType
Beta-2 adrenergic receptor (Humans)protein
primary
Beta adrenergic receptor (Humans)protein
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
CarteololapprovedyestargetantagonistDetails
OrciprenalineapprovedyestargetagonistDetails
Ritodrineapproved, investigationalyestargetagonistDetails
TerbutalineapprovedyestargetagonistDetails
BitolterolwithdrawnyestargetDetails
SalmeterolapprovedyestargetagonistDetails
Formoterolapproved, investigationalyestargetagonistDetails
Albuterolapproved, vet_approvedyestargetagonistDetails
TimololapprovedyestargetantagonistDetails
Propranololapproved, investigationalunknowntargetantagonistDetails
LabetalolapprovedyestargetantagonistDetails
BisoprololapprovednotargetantagonistDetails
Epinephrineapproved, vet_approvedyestargetagonistDetails
Pseudoephedrineapprovedunknowntargetpartial agonistDetails
Alprenololexperimental, withdrawnyestargetantagonistDetails
Pindololapproved, investigationalyestargetpartial agonistDetails
Isoprenalineapproved, investigationalyestargetagonistbinderDetails
Desipramineapproved, investigationalunknowntargetantagonistDetails
NadololapprovedunknowntargetantagonistDetails
LevobunololapprovedyestargetantagonistDetails
MetipranololapprovedyestargetantagonistDetails
Arformoterolapproved, investigationalyestargetagonistDetails
Procaterolapproved, investigationalyestargetagonistDetails
Clenbuterolapproved, investigational, vet_approvedyestargetagonistDetails
Carvedilolapproved, investigationalunknowntargetantagonistDetails
Fenoterolapproved, investigationalyestargetagonistDetails
PirbuterolapprovedyestargetagonistDetails
OxprenololapprovedunknowntargetantagonistDetails
Penbutololapproved, investigationalyestargetantagonistpartial agonistDetails
NorepinephrineapprovedyestargetagonistDetails
BambuterolinvestigationalyestargetagonistDetails
IndacaterolapprovedyestargetagonistDetails
NCX 950investigationalunknowntargetDetails
Droxidopaapproved, investigationalyestargetagonistDetails
PW2101investigationalunknowntargetDetails
Metoprololapproved, investigationalnotargetantagonistDetails
Betaxololapproved, investigationalunknowntargetantagonistDetails
SotalolapprovedyestargetantagonistDetails
BevantololexperimentalunknowntargetantagonistDetails
Acebutololapproved, investigationalunknowntargetpartial agonistDetails
ArbutamineapprovedunknowntargetagonistDetails
DobutamineapprovedunknowntargetagonistDetails
(S)-carazololexperimentalunknowntargetDetails
DipivefrinapprovedyestargetagonistDetails
Bopindololexperimentalyestargetantagonistpartial agonistDetails
BupranololexperimentalunknowntargetantagonistDetails
Nebivololapproved, investigationalunknowntargetantagonistDetails
PhenoxybenzamineapprovedunknowntargetDetails
Ephedra sinica rootnutraceuticalyestargetagonistDetails
AsenapineapprovedunknowntargetantagonistDetails
CabergolineapprovedunknowntargetbinderDetails
IsoetharineapprovedunknowntargetagonistDetails
AtenololapprovedunknowntargetantagonistDetails
Phenylpropanolamineapproved, vet_approved, withdrawnunknowntargetagonistDetails
OlodaterolapprovedyestargetagonistDetails
VilanterolapprovedyestargetagonistDetails
Celiprololapproved, investigationalyestargetagonistDetails
Levosalbutamolapproved, investigationalyestargetagonistDetails
BefunololexperimentalunknowntargetDetails
TulobuterolinvestigationalunknowntargetregulatorDetails
PutrescineexperimentalunknowntargetDetails
SpermidineexperimentalunknowntargetDetails
Spermineexperimental, nutraceuticalunknowntargetDetails
PropafenoneapprovedunknowntargetantagonistDetails
ArotinololinvestigationalyestargetantagonistDetails
DoxofyllineexperimentalyestargetagonistDetails
Protokylolapproved, vet_approvedyestargetagonistDetails
RacepinephrineapprovedyestargetagonistDetails
EtafedrineapprovedyestargetagonistDetails
BedoradrineinvestigationalyestargetagonistDetails
Aripiprazoleapproved, investigationalunknowntargetligandDetails
EphedrineapprovedyestargetagonistDetails
Viloxazineapproved, investigational, withdrawnunknowntargetantagonistDetails
MethoxyphenamineapprovedunknowntargetregulatorDetails
IloperidoneapprovedunknowntargetantagonistDetails
DichloroisoproterenolinvestigationalyestargetinhibitorDetails
PF-00610355investigationalyestargetagonistDetails
CarmoterolexperimentalyestargetagonistDetails
APD-209investigationalyestargetagonistDetails
AbediterolinvestigationalyestargetagonistDetails
BatefenterolinvestigationalyestargetmodulatorDetails
BucindololinvestigationalyestargetmodulatorDetails
Amiodaroneapproved, investigationalyestargetinhibitordownregulatorDetails
Amphetamineapproved, illicit, investigationalunknowntargetagonistDetails
NortriptylineapprovedunknowntargetantagonistDetails
TrimipramineapprovedunknowntargetbinderDetails
Olanzapineapproved, investigationalnotargetinhibitorDetails
BethanidineapprovedunknowntargetantagonistDetails
MephentermineapprovedunknowntargetagonistDetails
BufuralolexperimentalunknowntargetantagonistDetails
Dihydroergocristineapproved, experimentalyestargetantagonistagonistDetails
Ergoloid mesylateapprovedyestargetantagonistagonistDetails
DihydroergocornineapprovedyestargetantagonistagonistDetails
DL-MethylephedrineapprovedyestargetagonistDetails
Paroxetineapproved, investigationalunknowntargetinhibitorDetails
CryptenamineapprovedunknowntargetinhibitorpotentiatorDetails
Ritodrineapproved, investigationalyestargetagonistdownregulatorDetails
Metoprololapproved, investigationalunknowntargetinhibitorDetails