ID ADRB2_HUMAN Reviewed; 413 AA. AC P07550; B0LPE4; B2R7X2; O14823; O14824; O14825; O14826; Q4JG18; AC Q53GA6; Q6GMT4; Q6P4D8; Q8NEQ9; Q96EC3; Q9UCZ0; Q9UCZ1; Q9UCZ2; AC Q9UCZ3; Q9UH95; Q9UHA1; Q9UMZ5; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 3. DT 03-SEP-2014, entry version 176. DE RecName: Full=Beta-2 adrenergic receptor; DE AltName: Full=Beta-2 adrenoreceptor; DE Short=Beta-2 adrenoceptor; GN Name=ADRB2; Synonyms=ADRB2R, B2AR; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLN-27. RC TISSUE=Brain; RX PubMed=3026848; DOI=10.1016/0014-5793(87)81436-9; RA Chung F.-Z., Lentes K.-U., Gocayne J.D., Fitzgerald M.G., RA Robinson D.A., Kerlavage A.R., Fraser C.M., Venter J.C.; RT "Cloning and sequence analysis of the human brain beta-adrenergic RT receptor. Evolutionary relationship to rodent and avian beta-receptors RT and porcine muscarinic receptors."; RL FEBS Lett. 211:200-206(1987). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-16 AND GLN-27. RX PubMed=3034889; RA Kobilka B.K., Frielle T., Dohlman H.G., Bolanowski M.A., Dixon R.A.F., RA Keller P., Caron M.G., Lefkowitz R.J.; RT "Delineation of the intronless nature of the genes for the human and RT hamster beta 2-adrenergic receptor and their putative promoter RT regions."; RL J. Biol. Chem. 262:7321-7327(1987). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-16 AND GLN-27. RX PubMed=3033609; DOI=10.1093/nar/15.8.3636; RA Schofield P.R., Rhee L.M., Peralta E.G.; RT "Primary structure of the human beta-adrenergic receptor gene."; RL Nucleic Acids Res. 15:3636-3636(1987). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ARG-16 AND GLN-27. RX PubMed=3025863; DOI=10.1073/pnas.84.1.46; RA Kobilka B.K., Dixon R.A.F., Frielle T., Dohlman H.G., Bolanowski M.A., RA Sigal I.S., Yang-Feng T.L., Francke U., Caron M.G., Lefkowitz R.J.; RT "cDNA for the human beta 2-adrenergic receptor: a protein with RT multiple membrane-spanning domains and encoded by a gene whose RT chromosomal location is shared with that of the receptor for platelet- RT derived growth factor."; RL Proc. Natl. Acad. Sci. U.S.A. 84:46-50(1987). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-27. RX PubMed=2823249; DOI=10.1073/pnas.84.20.6995; RA Emorine L.J., Marullo S., Delavier-Klutchko C., Kaveri S.V., RA Durieu-Trautmann O., Strosberg A.D.; RT "Structure of the gene for human beta 2-adrenergic receptor: RT expression and promoter characterization."; RL Proc. Natl. Acad. Sci. U.S.A. 84:6995-6999(1987). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-16; GLN-27; MET-34 RP AND ILE-164. RX PubMed=8383511; DOI=10.1165/ajrcmb/8.3.334; RA Reihsaus E., Innis M., Macintyre N., Liggett S.B.; RT "Mutations in the gene encoding for the beta 2-adrenergic receptor in RT normal and asthmatic subjects."; RL Am. J. Respir. Cell Mol. Biol. 8:334-339(1993). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLN-27; LEU-159; RP PHE-159 AND ARG-375. RC TISSUE=Blood; RX PubMed=11246467; DOI=10.1046/j.1469-1809.2000.6420135.x; RA Rupert J.L., Monsalve M.V., Devine D.V., Hochachka P.W.; RT "Beta2-adrenergic receptor allele frequencies in the Quechua, a high RT altitude native population."; RL Ann. Hum. Genet. 64:135-143(2000). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ARG-16 AND RP GLN-27. RC TISSUE=Heart; RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.; RT "cDNA clones of human proteins involved in signal transduction RT sequenced by the Guthrie cDNA resource center (www.cdna.org)."; RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-27. RC TISSUE=Thyroid; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLN-27 AND CYS-220. RG SeattleSNPs variation discovery resource; RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-27. RG NHLBI resequencing and genotyping service (RS&G); RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases. RN [13] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [14] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ARG-16 AND RP GLN-27. RC TISSUE=Fetal brain, Leukocyte, and Prostate; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [15] RP MUTAGENESIS OF ASP-79. RX PubMed=2831218; RA Chung F.-Z., Wang C.-D., Potter P.C., Venter J.C., Fraser C.M.; RT "Site-directed mutagenesis and continuous expression of human beta- RT adrenergic receptors. Identification of a conserved aspartate residue RT involved in agonist binding and receptor activation."; RL J. Biol. Chem. 263:4052-4055(1988). RN [16] RP PALMITOYLATION AT CYS-341, AND MUTAGENESIS OF CYS-341. RX PubMed=2540197; RA O'Dowd B.F., Hnatowich M., Caron M.G., Lefkowitz R.J., Bouvier M.; RT "Palmitoylation of the human beta 2-adrenergic receptor. Mutation of RT Cys341 in the carboxyl tail leads to an uncoupled nonpalmitoylated RT form of the receptor."; RL J. Biol. Chem. 264:7564-7569(1989). RN [17] RP MUTAGENESIS OF TYR-141; TYR-350; TYR-354 AND TYR-366, AND RP PHOSPHORYLATION AT TYR-141. RX PubMed=8521811; RA Valiquette M., Parent S., Loisel T.P., Bouvier M.; RT "Mutation of tyrosine-141 inhibits insulin-promoted tyrosine RT phosphorylation and increased responsiveness of the human beta 2- RT adrenergic receptor."; RL EMBO J. 14:5542-5549(1995). RN [18] RP INTERACTION WITH ARRB1 AND ARRB2. RX PubMed=7822302; DOI=10.1074/jbc.270.2.720; RA Gurevich V.V., Dion S.B., Onorato J.J., Ptasienski J., Kim C.M., RA Sterne-Marr R., Hosey M.M., Benovic J.L.; RT "Arrestin interactions with G protein-coupled receptors. Direct RT binding studies of wild type and mutant arrestins with rhodopsin, beta RT 2-adrenergic, and m2 muscarinic cholinergic receptors."; RL J. Biol. Chem. 270:720-731(1995). RN [19] RP INTERACTION WITH ARRB1. RX PubMed=9388255; DOI=10.1074/jbc.272.49.31051; RA Lin F.-T., Krueger K.M., Kendall H.E., Daaka Y., Fredericks Z.L., RA Pitcher J.A., Lefkowitz R.J.; RT "Clathrin-mediated endocytosis of the beta-adrenergic receptor is RT regulated by phosphorylation/dephosphorylation of beta-arrestin1."; RL J. Biol. Chem. 272:31051-31057(1997). RN [20] RP INTERACTION WITH SLC9A3R1. RX PubMed=10499588; DOI=10.1038/45816; RA Cao T.T., Deacon H.W., Reczek D., Bretscher A., von Zastrow M.; RT "A kinase-regulated PDZ-domain interaction controls endocytic sorting RT of the beta2-adrenergic receptor."; RL Nature 401:286-290(1999). RN [21] RP INTERACTION WITH SRC AND ARRB1. RX PubMed=9924018; DOI=10.1126/science.283.5402.655; RA Luttrell L.M., Ferguson S.S.G., Daaka Y., Miller W.E., Maudsley S., RA Della Rocca G.J., Lin F.-T., Kawakatsu H., Owada K., Luttrell D.K., RA Caron M.G., Lefkowitz R.J.; RT "Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src RT protein kinase complexes."; RL Science 283:655-661(1999). RN [22] RP EFFECT OF PALMITOYLATION, PHOSPHORYLATION AT SER-345 AND SER-346, AND RP MUTAGENESIS OF 345-SER-SER-346. RX PubMed=11146000; DOI=10.1046/j.1471-4159.2001.00005.x; RA Moffett S., Rousseau G., Lagace M., Bouvier M.; RT "The palmitoylation state of the beta(2)-adrenergic receptor regulates RT the synergistic action of cyclic AMP-dependent protein kinase and RT beta-adrenergic receptor kinase involved in its phosphorylation and RT desensitization."; RL J. Neurochem. 76:269-279(2001). RN [23] RP INTERACTION WITH GPRASP1. RX PubMed=12142540; DOI=10.1126/science.1073308; RA Whistler J.L., Enquist J., Marley A., Fong J., Gladher F., Tsuruda P., RA Murray S.R., Von Zastrow M.; RT "Modulation of postendocytic sorting of G protein-coupled receptors."; RL Science 297:615-620(2002). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-246, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [25] RP UBIQUITINATION, DEUBIQUITINATION BY USP20 AND USP33, AND INTERACTION RP WITH USP20 AND USP33. RX PubMed=19424180; DOI=10.1038/emboj.2009.128; RA Berthouze M., Venkataramanan V., Li Y., Shenoy S.K.; RT "The deubiquitinases USP33 and USP20 coordinate beta2 adrenergic RT receptor recycling and resensitization."; RL EMBO J. 28:1684-1696(2009). RN [26] RP INTERACTION WITH EGLN3 AND VHL, SUBCELLULAR LOCATION, INDUCTION, RP UBIQUITINATION, HYDROXYLATION AT PRO-382 AND PRO-395, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=19584355; DOI=10.1126/scisignal.2000444; RA Xie L., Xiao K., Whalen E.J., Forrester M.T., Freeman R.S., Fong G., RA Gygi S.P., Lefkowitz R.J., Stamler J.S.; RT "Oxygen-regulated beta(2)-adrenergic receptor hydroxylation by EGLN3 RT and ubiquitylation by pVHL."; RL Sci. Signal. 2:RA33-RA33(2009). RN [27] RP INTERACTION WITH SNX27. RX PubMed=20733053; DOI=10.1083/jcb.201004060; RA Lauffer B.E., Melero C., Temkin P., Lei C., Hong W., Kortemme T., RA von Zastrow M.; RT "SNX27 mediates PDZ-directed sorting from endosomes to the plasma RT membrane."; RL J. Cell Biol. 190:565-574(2010). RN [28] RP INTERACTION WITH SNX27. RX PubMed=21602791; DOI=10.1038/ncb2252; RA Temkin P., Lauffer B., Jager S., Cimermancic P., Krogan N.J., RA von Zastrow M.; RT "SNX27 mediates retromer tubule entry and endosome-to-plasma membrane RT trafficking of signalling receptors."; RL Nat. Cell Biol. 13:715-721(2011). RN [29] RP X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 1-365 IN COMPLEX WITH RP CARAZOLOL, AND TOPOLOGY. RX PubMed=17952055; DOI=10.1038/nature06325; RA Rasmussen S.G.F., Choi H.-J., Rosenbaum D.M., Kobilka T.S., RA Thian F.S., Edwards P.C., Burghammer M., Ratnala V.R.P., RA Sanishvili R., Fischetti R.F., Schertler G.F.X., Weis W.I., RA Kobilka B.K.; RT "Crystal structure of the human beta2 adrenergic G-protein-coupled RT receptor."; RL Nature 450:383-387(2007). RN [30] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-365 IN COMPLEX WITH RP CARAZOLOL AND CHOLESTEROL, DISULFIDE BONDS, TOPOLOGY, AND RP PALMITOYLATION AT CYS-341. RX PubMed=17962520; DOI=10.1126/science.1150577; RA Cherezov V., Rosenbaum D.M., Hanson M.A., Rasmussen S.G.F., RA Thian F.S., Kobilka T.S., Choi H.-J., Kuhn P., Weis W.I., RA Kobilka B.K., Stevens R.C.; RT "High-resolution crystal structure of an engineered human beta2- RT adrenergic G protein-coupled receptor."; RL Science 318:1258-1265(2007). RN [31] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-365 IN COMPLEX WITH TIMOLOL RP AND CHOLESTEROL, DISULFIDE BONDS, TOPOLOGY, AND PALMITOYLATION AT RP CYS-341. RX PubMed=18547522; DOI=10.1016/j.str.2008.05.001; RA Hanson M.A., Cherezov V., Griffith M.T., Roth C.B., Jaakola V.P., RA Chien E.Y., Velasquez J., Kuhn P., Stevens R.C.; RT "A specific cholesterol binding site is established by the 2.8 A RT structure of the human beta2-adrenergic receptor."; RL Structure 16:897-905(2008). RN [32] RP VARIANTS ARG-16 AND GLN-27, AND CHARACTERIZATION. RX PubMed=7915137; DOI=10.1021/bi00198a006; RA Green S.A., Turki J., Innis M., Ligget S.B.; RT "Amino-terminal polymorphisms of the human beta 2-adrenergic receptor RT impart distinct agonist-promoted regulatory properties."; RL Biochemistry 33:9414-9419(1994). RN [33] RP VARIANT ARG-16, AND POLYMORPHISM. RX PubMed=7706471; DOI=10.1172/JCI117838; RA Turki J., Pak J., Green S.A., Martin R.J., Liggett S.B.; RT "Genetic polymorphisms of the beta 2-adrenergic receptor in nocturnal RT and nonnocturnal asthma. Evidence that Gly16 correlates with the RT nocturnal phenotype."; RL J. Clin. Invest. 95:1635-1641(1995). CC -!- FUNCTION: Beta-adrenergic receptors mediate the catecholamine- CC induced activation of adenylate cyclase through the action of G CC proteins. The beta-2-adrenergic receptor binds epinephrine with an CC approximately 30-fold greater affinity than it does CC norepinephrine. CC -!- SUBUNIT: Binds SLC9A3R1 and GPRASP1. Interacts with ARRB1 and CC ARRB2. Interacts with SRC, USP20 and USP33. Interacts with VHL; CC the interaction, which is increased on hydroxylation of ADRB2, CC ubiquitinates ADRB2 leading to its degradation. Interacts with CC EGLN3; the interaction hydroxylates ADRB2 facilitating VHL-E3 CC ligase-mediated ubiquitination. Interacts (via PDZ-binding motif) CC with SNX27 (via PDZ domain); the interaction is required when CC endocytosed to prevent degradation in lysosomes and promote CC recycling to the plasma membrane. CC -!- INTERACTION: CC Q5TCQ9:MAGI3; NbExp=9; IntAct=EBI-491169, EBI-310506; CC O14745:SLC9A3R1; NbExp=6; IntAct=EBI-491169, EBI-349787; CC P12931:SRC; NbExp=3; IntAct=EBI-491169, EBI-621482; CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. CC Note=Colocalizes with VHL at the cell membrane. CC -!- PTM: Palmitoylated; may reduce accessibility of Ser-345 and Ser- CC 346 by anchoring Cys-341 to the plasma membrane. Agonist CC stimulation promotes depalmitoylation and further allows Ser-345 CC and Ser-346 phosphorylation. CC -!- PTM: Phosphorylated by PKA and BARK upon agonist stimulation, CC which mediates homologous desensitization of the receptor. PKA- CC mediated phosphorylation seems to facilitate phosphorylation by CC BARK. CC -!- PTM: Phosphorylation of Tyr-141 is induced by insulin and leads to CC supersensitization of the receptor. CC -!- PTM: Polyubiquitinated. Agonist-induced ubiquitination leads to CC sort internalized receptors to the lysosomes for degradation. CC Deubiquitination by USP20 and USP33, leads to ADRB2 recycling and CC resensitization after prolonged agonist stimulation. USP20 and CC USP33 are constitutively associated and are dissociated CC immediately after agonist stimulation. Ubiquitination by the VHL- CC E3 ligase complex is oxygen-dependent. CC -!- PTM: Hydroxylation by EGLN3 occurs only under normoxia and CC increases the interaction with VHL and the subsequent CC ubiquitination and degradation of ADRB2. CC -!- POLYMORPHISM: The Gly-16 allele is overrepresented in individuals CC affected by nocturnal asthma as compared to controls, and appears CC to be an important genetic factor in the expression of this CC asthmatic phenotype. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC Adrenergic receptor subfamily. ADRB2 sub-subfamily. CC -!- SEQUENCE CAUTION: CC Sequence=BAD96745.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/adrb2/"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X04827; CAA28511.1; -; mRNA. DR EMBL; Y00106; CAA68289.1; -; Genomic_DNA. DR EMBL; M15169; AAA88015.1; -; mRNA. DR EMBL; J02960; AAA88017.1; -; Genomic_DNA. DR EMBL; AF022953; AAB82148.1; -; Genomic_DNA. DR EMBL; AF022954; AAB82149.1; -; Genomic_DNA. DR EMBL; AF022955; AAB82150.1; -; Genomic_DNA. DR EMBL; AF022956; AAB82151.1; -; Genomic_DNA. DR EMBL; AF169225; AAD48036.1; -; Genomic_DNA. DR EMBL; AF202305; AAF17569.1; -; Genomic_DNA. DR EMBL; AF203386; AAF20199.1; -; Genomic_DNA. DR EMBL; AY136741; AAN01267.1; -; mRNA. DR EMBL; AK313151; BAG35969.1; -; mRNA. DR EMBL; AK223025; BAD96745.1; ALT_INIT; mRNA. DR EMBL; DQ094845; AAY88739.1; -; Genomic_DNA. DR EMBL; EU332834; ABY87523.1; -; Genomic_DNA. DR EMBL; CH471062; EAW61798.1; -; Genomic_DNA. DR EMBL; BC012481; AAH12481.3; -; mRNA. DR EMBL; BC063486; AAH63486.2; -; mRNA. DR EMBL; BC073856; AAH73856.1; -; mRNA. DR CCDS; CCDS4292.1; -. DR PIR; A27525; QRHUB2. DR RefSeq; NP_000015.1; NM_000024.5. DR UniGene; Hs.2551; -. DR PDB; 1GQ4; X-ray; 1.90 A; A=409-413. DR PDB; 2R4R; X-ray; 3.40 A; A=1-365. DR PDB; 2R4S; X-ray; 3.40 A; A=24-365. DR PDB; 2RH1; X-ray; 2.40 A; A=1-230, A=263-365. DR PDB; 3D4S; X-ray; 2.80 A; A=1-230, A=263-348. DR PDB; 3KJ6; X-ray; 3.40 A; A=2-365. DR PDB; 3NY8; X-ray; 2.84 A; A=1-230, A=263-348. DR PDB; 3NY9; X-ray; 2.84 A; A=1-230, A=263-348. DR PDB; 3NYA; X-ray; 3.16 A; A=1-230, A=263-348. DR PDB; 3P0G; X-ray; 3.50 A; A=1-230, A=263-365. DR PDB; 3PDS; X-ray; 3.50 A; A=25-230, A=264-348. DR PDB; 3SN6; X-ray; 3.20 A; R=29-365. DR PDB; 4GBR; X-ray; 3.99 A; A=29-365. DR PDB; 4LDE; X-ray; 2.79 A; A=29-348. DR PDB; 4LDL; X-ray; 3.10 A; A=29-348. DR PDB; 4LDO; X-ray; 3.20 A; A=29-348. DR PDBsum; 1GQ4; -. DR PDBsum; 2R4R; -. DR PDBsum; 2R4S; -. DR PDBsum; 2RH1; -. DR PDBsum; 3D4S; -. DR PDBsum; 3KJ6; -. DR PDBsum; 3NY8; -. DR PDBsum; 3NY9; -. DR PDBsum; 3NYA; -. DR PDBsum; 3P0G; -. DR PDBsum; 3PDS; -. DR PDBsum; 3SN6; -. DR PDBsum; 4GBR; -. DR PDBsum; 4LDE; -. DR PDBsum; 4LDL; -. DR PDBsum; 4LDO; -. DR ProteinModelPortal; P07550; -. DR SMR; P07550; 29-341. DR BioGrid; 106663; 237. DR DIP; DIP-33948N; -. DR IntAct; P07550; 11. DR MINT; MINT-148142; -. DR BindingDB; P07550; -. DR ChEMBL; CHEMBL2096974; -. DR DrugBank; DB00866; Alprenolol. DR DrugBank; DB01274; Arformoterol. DR DrugBank; DB01408; Bambuterol. DR DrugBank; DB00612; Bisoprolol. DR DrugBank; DB00901; Bitolterol. DR DrugBank; DB01158; Bretylium. DR DrugBank; DB00521; Carteolol. DR DrugBank; DB01136; Carvedilol. DR DrugBank; DB01407; Clenbuterol. DR DrugBank; DB01151; Desipramine. DR DrugBank; DB00668; Epinephrine. DR DrugBank; DB01288; Fenoterol. DR DrugBank; DB00983; Formoterol. DR DrugBank; DB01064; Isoproterenol. DR DrugBank; DB00598; Labetalol. DR DrugBank; DB01210; Levobunolol. DR DrugBank; DB01214; Metipranolol. DR DrugBank; DB01203; Nadolol. DR DrugBank; DB00368; Norepinephrine. DR DrugBank; DB00816; Orciprenaline. DR DrugBank; DB01580; Oxprenolol. DR DrugBank; DB01359; Penbutolol. DR DrugBank; DB00960; Pindolol. DR DrugBank; DB01291; Pirbuterol. DR DrugBank; DB01366; Procaterol. DR DrugBank; DB00571; Propranolol. DR DrugBank; DB00852; Pseudoephedrine. DR DrugBank; DB00867; Ritodrine. DR DrugBank; DB01001; Salbutamol. DR DrugBank; DB00938; Salmeterol. DR DrugBank; DB00871; Terbutaline. DR DrugBank; DB00373; Timolol. DR GuidetoPHARMACOLOGY; 29; -. DR TCDB; 9.A.14.3.5; the g-protein-coupled receptor (gpcr) family. DR PhosphoSite; P07550; -. DR DMDM; 296439450; -. DR MaxQB; P07550; -. DR PaxDb; P07550; -. DR PRIDE; P07550; -. DR DNASU; 154; -. DR Ensembl; ENST00000305988; ENSP00000305372; ENSG00000169252. DR GeneID; 154; -. DR KEGG; hsa:154; -. DR UCSC; uc003lpr.2; human. DR CTD; 154; -. DR GeneCards; GC05P148186; -. DR HGNC; HGNC:286; ADRB2. DR HPA; HPA003431; -. DR MIM; 109690; gene+phenotype. DR neXtProt; NX_P07550; -. DR PharmGKB; PA39; -. DR eggNOG; NOG262978; -. DR HOVERGEN; HBG106962; -. DR InParanoid; P07550; -. DR KO; K04142; -. DR OMA; RVFQVAK; -. DR OrthoDB; EOG7BS4BS; -. DR PhylomeDB; P07550; -. DR TreeFam; TF316350; -. DR Reactome; REACT_16927; Adrenoceptors. DR Reactome; REACT_19327; G alpha (s) signalling events. DR SignaLink; P07550; -. DR EvolutionaryTrace; P07550; -. DR GeneWiki; Beta-2_adrenergic_receptor; -. DR GenomeRNAi; 154; -. DR NextBio; 613; -. DR PRO; PR:P07550; -. DR ArrayExpress; P07550; -. DR Bgee; P07550; -. DR Genevestigator; P07550; -. DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl. DR GO; GO:0005768; C:endosome; TAS:ProtInc. DR GO; GO:0005887; C:integral component of plasma membrane; IDA:BHF-UCL. DR GO; GO:0005764; C:lysosome; TAS:ProtInc. DR GO; GO:0005634; C:nucleus; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0043235; C:receptor complex; IDA:HGNC. DR GO; GO:0004941; F:beta2-adrenergic receptor activity; IDA:HGNC. DR GO; GO:0051380; F:norepinephrine binding; IDA:HGNC. DR GO; GO:0015459; F:potassium channel regulator activity; IDA:BHF-UCL. DR GO; GO:0005515; F:protein binding; IPI:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:HGNC. DR GO; GO:0007190; P:activation of adenylate cyclase activity; IDA:HGNC. DR GO; GO:0007171; P:activation of transmembrane receptor protein tyrosine kinase activity; TAS:ProtInc. DR GO; GO:0007189; P:adenylate cyclase-activating G-protein coupled receptor signaling pathway; IEA:Ensembl. DR GO; GO:0007188; P:adenylate cyclase-modulating G-protein coupled receptor signaling pathway; TAS:ProtInc. DR GO; GO:0071875; P:adrenergic receptor signaling pathway; IDA:GOC. DR GO; GO:0045453; P:bone resorption; IEA:Ensembl. DR GO; GO:0050873; P:brown fat cell differentiation; IEA:Ensembl. DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc. DR GO; GO:0002032; P:desensitization of G-protein coupled receptor protein signaling pathway by arrestin; IDA:HGNC. DR GO; GO:0002024; P:diet induced thermogenesis; IEA:Ensembl. DR GO; GO:0008333; P:endosome to lysosome transport; TAS:ProtInc. DR GO; GO:0031649; P:heat generation; IEA:Ensembl. DR GO; GO:0040015; P:negative regulation of multicellular organism growth; IEA:Ensembl. DR GO; GO:0045986; P:negative regulation of smooth muscle contraction; IEA:Ensembl. DR GO; GO:0030501; P:positive regulation of bone mineralization; IEA:Ensembl. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:HGNC. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IMP:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Ensembl. DR GO; GO:0006898; P:receptor-mediated endocytosis; IDA:HGNC. DR GO; GO:0002028; P:regulation of sodium ion transport; IEA:Ensembl. DR GO; GO:0042312; P:regulation of vasodilation; IEA:InterPro. DR GO; GO:0009409; P:response to cold; IEA:Ensembl. DR GO; GO:0002025; P:vasodilation by norepinephrine-epinephrine involved in regulation of systemic arterial blood pressure; IEA:Ensembl. DR Gene3D; 1.20.1070.10; -; 1. DR InterPro; IPR002233; ADR_fam. DR InterPro; IPR000332; ADRB2_rcpt. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR PANTHER; PTHR24248:SF21; PTHR24248:SF21; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR01103; ADRENERGICR. DR PRINTS; PR00562; ADRENRGCB2AR. DR PRINTS; PR00237; GPCRRHODOPSN. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Complete proteome; Disulfide bond; KW G-protein coupled receptor; Glycoprotein; Hydroxylation; Lipoprotein; KW Membrane; Palmitate; Phosphoprotein; Polymorphism; Receptor; KW Reference proteome; Transducer; Transmembrane; Transmembrane helix; KW Ubl conjugation. FT CHAIN 1 413 Beta-2 adrenergic receptor. FT /FTId=PRO_0000069130. FT TOPO_DOM 1 34 Extracellular. FT TRANSMEM 35 58 Helical; Name=1. FT TOPO_DOM 59 71 Cytoplasmic. FT TRANSMEM 72 95 Helical; Name=2. FT TOPO_DOM 96 106 Extracellular. FT TRANSMEM 107 129 Helical; Name=3. FT TOPO_DOM 130 150 Cytoplasmic. FT TRANSMEM 151 174 Helical; Name=4. FT TOPO_DOM 175 196 Extracellular. FT TRANSMEM 197 220 Helical; Name=5. FT TOPO_DOM 221 274 Cytoplasmic. FT TRANSMEM 275 298 Helical; Name=6. FT TOPO_DOM 299 305 Extracellular. FT TRANSMEM 306 329 Helical; Name=7. FT TOPO_DOM 330 413 Cytoplasmic. FT REGION 193 207 Agonist and antagonist binding. FT REGION 286 293 Agonist and antagonist binding. FT REGION 312 316 Agonist and antagonist binding. FT MOTIF 410 413 PDZ-binding. FT BINDING 113 113 Agonist or antagonist. FT BINDING 118 118 Agonist or antagonist. FT MOD_RES 141 141 Phosphotyrosine. FT MOD_RES 246 246 Phosphoserine. FT MOD_RES 261 261 Phosphoserine; by PKA (Potential). FT MOD_RES 262 262 Phosphoserine; by PKA (Potential). FT MOD_RES 345 345 Phosphoserine; by PKA. FT MOD_RES 346 346 Phosphoserine; by PKA. FT MOD_RES 355 355 Phosphoserine; by BARK (Probable). FT MOD_RES 356 356 Phosphoserine; by BARK (Probable). FT MOD_RES 382 382 4-hydroxyproline. FT MOD_RES 395 395 4-hydroxyproline. FT LIPID 341 341 S-palmitoyl cysteine. FT CARBOHYD 6 6 N-linked (GlcNAc...) (Probable). FT CARBOHYD 15 15 N-linked (GlcNAc...) (Probable). FT DISULFID 106 191 FT DISULFID 184 190 FT VARIANT 15 15 N -> S (in dbSNP:rs33973603). FT /FTId=VAR_049373. FT VARIANT 16 16 G -> R (common polymorphism; FT dbSNP:rs1042713). FT /FTId=VAR_003452. FT VARIANT 27 27 E -> Q (in dbSNP:rs1042714). FT /FTId=VAR_003453. FT VARIANT 34 34 V -> M. FT /FTId=VAR_003454. FT VARIANT 159 159 I -> F. FT /FTId=VAR_009125. FT VARIANT 159 159 I -> L. FT /FTId=VAR_009124. FT VARIANT 164 164 T -> I (in dbSNP:rs1800888). FT /FTId=VAR_003455. FT VARIANT 220 220 S -> C (in dbSNP:rs3729943). FT /FTId=VAR_025101. FT VARIANT 375 375 K -> R. FT /FTId=VAR_009394. FT MUTAGEN 79 79 D->N: Affects binding of catecholamines, FT and produces an uncoupling between the FT receptor and stimulatory G proteins. FT MUTAGEN 141 141 Y->F: Abolishes insulin-induced tyrosine FT phosphorylation and insulin-induced FT receptor supersensitization. FT MUTAGEN 341 341 C->G: Uncoupled receptor. FT MUTAGEN 345 346 SS->AA: Delayed agonist-promoted FT desensitization. FT MUTAGEN 350 350 Y->A: Does not affect insulin-induced FT tyrosine phosphorylation or insulin- FT induced receptor supersensitization. FT MUTAGEN 354 354 Y->A: Does not affect insulin-induced FT tyrosine phosphorylation or insulin- FT induced receptor supersensitization. FT MUTAGEN 366 366 Y->F: Does not affect insulin-induced FT tyrosine phosphorylation or insulin- FT induced receptor supersensitization. FT CONFLICT 71 71 F -> L (in Ref. 9; BAG35969). FT CONFLICT 216 216 V -> A (in Ref. 8; AAN01267). FT CONFLICT 261 261 S -> P (in Ref. 10; BAD96745). FT CONFLICT 402 402 Q -> P (in Ref. 14; AAH12481). FT STRAND 25 27 FT HELIX 31 60 FT HELIX 62 64 FT HELIX 67 85 FT HELIX 87 96 FT HELIX 102 136 FT STRAND 137 139 FT HELIX 147 170 FT TURN 171 174 FT HELIX 179 186 FT STRAND 187 189 FT HELIX 197 207 FT HELIX 209 229 FT TURN 235 239 FT TURN 263 265 FT HELIX 267 298 FT STRAND 299 303 FT HELIX 305 317 FT HELIX 318 320 FT HELIX 322 325 FT HELIX 326 328 FT HELIX 330 339 FT TURN 345 347 SQ SEQUENCE 413 AA; 46459 MW; 408C22731C6EDFBE CRC64; MGQPGNGSAF LLAPNGSHAP DHDVTQERDE VWVVGMGIVM SLIVLAIVFG NVLVITAIAK FERLQTVTNY FITSLACADL VMGLAVVPFG AAHILMKMWT FGNFWCEFWT SIDVLCVTAS IETLCVIAVD RYFAITSPFK YQSLLTKNKA RVIILMVWIV SGLTSFLPIQ MHWYRATHQE AINCYANETC CDFFTNQAYA IASSIVSFYV PLVIMVFVYS RVFQEAKRQL QKIDKSEGRF HVQNLSQVEQ DGRTGHGLRR SSKFCLKEHK ALKTLGIIMG TFTLCWLPFF IVNIVHVIQD NLIRKEVYIL LNWIGYVNSG FNPLIYCRSP DFRIAFQELL CLRRSSLKAY GNGYSSNGNT GEQSGYHVEQ EKENKLLCED LPGTEDFVGH QGTVPSDNID SQGRNCSTND SLL //