ID ADRB2_HUMAN Reviewed; 413 AA. AC P07550; B0LPE4; B2R7X2; O14823; O14824; O14825; O14826; Q4JG18; Q53GA6; AC Q6GMT4; Q6P4D8; Q8NEQ9; Q96EC3; Q9UCZ0; Q9UCZ1; Q9UCZ2; Q9UCZ3; Q9UH95; AC Q9UHA1; Q9UMZ5; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 3. DT 28-JAN-2026, entry version 258. DE RecName: Full=Beta-2 adrenergic receptor {ECO:0000303|PubMed:3034889}; DE AltName: Full=Beta-2 adrenoreceptor; DE Short=Beta-2 adrenoceptor; GN Name=ADRB2 {ECO:0000312|HGNC:HGNC:286}; Synonyms=ADRB2R, B2AR; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC 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., Robinson D.A., RA Kerlavage A.R., Fraser C.M., Venter J.C.; RT "Cloning and sequence analysis of the human brain beta-adrenergic receptor. RT Evolutionary relationship to rodent and avian beta-receptors and porcine RT 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; DOI=10.1016/s0021-9258(18)48239-7; 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 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 multiple RT membrane-spanning domains and encoded by a gene whose chromosomal location RT is shared with that of the receptor for platelet-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: expression and RT 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 AND RP 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; PHE-159 RP AND ARG-375. RC TISSUE=Blood; RX PubMed=11246467; DOI=10.1017/s0003480000008009; 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 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 sequenced by RT 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., 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 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [15] RP MUTAGENESIS OF ASP-79, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=2831218; DOI=10.1016/s0021-9258(18)68888-x; 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; DOI=10.1016/s0021-9258(18)83271-9; 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 Cys341 RT in the carboxyl tail leads to an uncoupled nonpalmitoylated form of the RT receptor."; RL J. Biol. Chem. 264:7564-7569(1989). RN [17] RP MUTAGENESIS OF TYR-141; TYR-350; TYR-354 AND TYR-366, AND PHOSPHORYLATION RP AT TYR-141. RX PubMed=8521811; DOI=10.1002/j.1460-2075.1995.tb00241.x; 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-adrenergic RT 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 binding RT studies of wild type and mutant arrestins with rhodopsin, beta 2- RT 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 regulated RT by phosphorylation/dephosphorylation of beta-arrestin1."; RL J. Biol. Chem. 272:31051-31057(1997). RN [20] RP FUNCTION, INTERACTION WITH NHERF1, AND MUTAGENESIS OF LEU-413. RX PubMed=9560162; DOI=10.1038/33458; RA Hall R.A., Premont R.T., Chow C.-W., Blitzer J.T., Pitcher J.A., Claing A., RA Stoffel R.H., Barak L.S., Shenolikar S., Weinman E.J., Grinstein S., RA Lefkowitz R.J.; RT "The beta2-adrenergic receptor interacts with the Na+/H+-exchanger RT regulatory factor to control Na+/H+ exchange."; RL Nature 392:626-630(1998). RN [21] RP INTERACTION WITH NHERF1. 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 of RT the beta2-adrenergic receptor."; RL Nature 401:286-290(1999). RN [22] 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 protein RT kinase complexes."; RL Science 283:655-661(1999). RN [23] 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 the RT synergistic action of cyclic AMP-dependent protein kinase and beta- RT adrenergic receptor kinase involved in its phosphorylation and RT desensitization."; RL J. Neurochem. 76:269-279(2001). RN [24] RP PHOSPHORYLATION AT SER-355 AND SER-356. RX PubMed=18056263; DOI=10.1074/jbc.m705747200; RA Wang Y., De Arcangelis V., Gao X., Ramani B., Jung Y.S., Xiang Y.; RT "Norepinephrine- and epinephrine-induced distinct beta2-adrenoceptor RT signaling is dictated by GRK2 phosphorylation in cardiomyocytes."; RL J. Biol. Chem. 283:1799-1807(2008). RN [25] 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 [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-246, AND IDENTIFICATION BY RP 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, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA 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 [27] RP UBIQUITINATION, DEUBIQUITINATION BY USP20 AND USP33, AND INTERACTION WITH RP 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 receptor RT recycling and resensitization."; RL EMBO J. 28:1684-1696(2009). RN [28] RP INTERACTION WITH EGLN3 AND VHL, SUBCELLULAR LOCATION, INDUCTION, RP UBIQUITINATION, HYDROXYLATION AT PRO-382 AND PRO-395, AND IDENTIFICATION BY RP 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 and RT ubiquitylation by pVHL."; RL Sci. Signal. 2:RA33-RA33(2009). RN [29] RP UBIQUITINATION, SUBCELLULAR LOCATION, AND INTERACTION WITH ARRDC3. RX PubMed=20559325; DOI=10.1038/embor.2010.80; RA Nabhan J.F., Pan H., Lu Q.; RT "Arrestin domain-containing protein 3 recruits the NEDD4 E3 ligase to RT mediate ubiquitination of the beta2-adrenergic receptor."; RL EMBO Rep. 11:605-611(2010). RN [30] 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 [31] 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 [32] RP INTERACTION WITH MARCHF2; NEDD4; USP20 AND USP33, SUBCELLULAR LOCATION, AND RP UBIQUITINATION. RX PubMed=23166351; DOI=10.1083/jcb.201208192; RA Han S.O., Xiao K., Kim J., Wu J.H., Wisler J.W., Nakamura N., RA Freedman N.J., Shenoy S.K.; RT "MARCH2 promotes endocytosis and lysosomal sorting of carvedilol-bound RT beta(2)-adrenergic receptors."; RL J. Cell Biol. 199:817-830(2012). RN [33] RP SUBCELLULAR LOCATION, AND INTERACTION WITH ARRDC3. RX PubMed=25220262; DOI=10.1002/pro.2549; RA Qi S., O'Hayre M., Gutkind J.S., Hurley J.H.; RT "Insights into beta2-adrenergic receptor binding from structures of the N- RT terminal lobe of ARRDC3."; RL Protein Sci. 23:1708-1716(2014). RN [34] RP INTERACTION WITH CNIH4. RX PubMed=24405750; DOI=10.1111/tra.12148; RA Sauvageau E., Rochdi M.D., Oueslati M., Hamdan F.F., Percherancier Y., RA Simpson J.C., Pepperkok R., Bouvier M.; RT "CNIH4 interacts with newly synthesized GPCR and controls their export from RT the endoplasmic reticulum."; RL Traffic 15:383-400(2014). RN [35] RP SUBCELLULAR LOCATION, PALMITOYLATION AT CYS-265 AND CYS-341, AND RP MUTAGENESIS OF CYS-265 AND CYS-341. RX PubMed=27481942; DOI=10.1074/jbc.m116.725762; RA Adachi N., Hess D.T., McLaughlin P., Stamler J.S.; RT "S-Palmitoylation of a Novel Site in the beta2-Adrenergic Receptor RT Associated with a Novel Intracellular Itinerary."; RL J. Biol. Chem. 291:20232-20246(2016). RN [36] RP FUNCTION, AND MUTAGENESIS OF TYR-174 AND ASP-300. RX PubMed=33093660; DOI=10.1038/s41422-020-00424-2; RA Xu X., Kaindl J., Clark M.J., Hubner H., Hirata K., Sunahara R.K., RA Gmeiner P., Kobilka B.K., Liu X.; RT "Binding pathway determines norepinephrine selectivity for the human RT beta1AR over beta2AR."; RL Cell Res. 31:569-579(2021). RN [37] {ECO:0007744|PDB:2R4R, ECO:0007744|PDB:2R4S} RP X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 1-365 IN COMPLEX WITH CARAZOLOL, RP AND TOPOLOGY. RX PubMed=17952055; DOI=10.1038/nature06325; RA Rasmussen S.G.F., Choi H.-J., Rosenbaum D.M., Kobilka T.S., Thian F.S., RA Edwards P.C., Burghammer M., Ratnala V.R.P., Sanishvili R., Fischetti R.F., RA Schertler G.F.X., Weis W.I., Kobilka B.K.; RT "Crystal structure of the human beta2 adrenergic G-protein-coupled RT receptor."; RL Nature 450:383-387(2007). RN [38] {ECO:0007744|PDB:2RH1} RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-365 IN COMPLEX WITH CARAZOLOL RP AND CHOLESTEROL, DISULFIDE BONDS, TOPOLOGY, AND 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., Thian F.S., RA Kobilka T.S., Choi H.-J., Kuhn P., Weis W.I., Kobilka B.K., Stevens R.C.; RT "High-resolution crystal structure of an engineered human beta2-adrenergic RT G protein-coupled receptor."; RL Science 318:1258-1265(2007). RN [39] {ECO:0007744|PDB:3D4S} RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-365 IN COMPLEX WITH TIMOLOL AND RP CHOLESTEROL, DISULFIDE BONDS, TOPOLOGY, AND PALMITOYLATION AT 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 structure RT of the human beta2-adrenergic receptor."; RL Structure 16:897-905(2008). RN [40] {ECO:0007744|PDB:4LDE, ECO:0007744|PDB:4LDL, ECO:0007744|PDB:4LDO} RP X-RAY CRYSTALLOGRAPHY (2.79 ANGSTROMS) OF 29-348 IN COMPLEX WITH RP (R)-ADRENALINE AND G PROTEINS, AND DISULFIDE BONDS. RX PubMed=24056936; DOI=10.1038/nature12572; RA Ring A.M., Manglik A., Kruse A.C., Enos M.D., Weis W.I., Garcia K.C., RA Kobilka B.K.; RT "Adrenaline-activated structure of beta2-adrenoceptor stabilized by an RT engineered nanobody."; RL Nature 502:575-579(2013). RN [41] RP VARIANTS ARG-16 AND GLN-27, CHARACTERIZATION, FUNCTION, AND SUBCELLULAR RP LOCATION. 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 [42] 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 and RT nonnocturnal asthma. Evidence that Gly16 correlates with the nocturnal RT phenotype."; RL J. Clin. Invest. 95:1635-1641(1995). CC -!- FUNCTION: G protein-coupled receptor for catecholamines that couples to CC both G(s) and G(i) proteins, activating bifurcated signaling pathways CC (PubMed:2831218, PubMed:7915137). ADRB2 binds epinephrine (Epi) with an CC approximately 30-fold greater affinity than norepinephrine (NE) CC (PubMed:2831218, PubMed:33093660, PubMed:7915137). In the heart, CC Epi- and NE-activated ADRB2 induces rapid and slow cardiomyocyte CC contraction rate, respectively (By similarity). Both NE and Epi promote CC coupling to G(s)/PKA pathway to regulate myocyte contraction rate (By CC similarity). Epi also promotes ADRB2 coupling to G(i) proteins to exert CC cardioprotective effects especially in the conditions of hypoxia and CC oxidative stress through the G(i)/PI3K/Akt signaling pathway (By CC similarity). ADRB2-G(s) signaling delivers proapoptotic signals in CC cardiomyocytes although G(i)-mediated survival effect appears to CC predominate (By similarity). ADRB2 also transduces signals CC independently of PKA to regulate cellular pH by modulating Na(+)/H(+) CC exchanger SLC9A3 function (PubMed:9560162). CC {ECO:0000250|UniProtKB:P18762, ECO:0000269|PubMed:2831218, CC ECO:0000269|PubMed:33093660, ECO:0000269|PubMed:7915137, CC ECO:0000269|PubMed:9560162}. CC -!- SUBUNIT: Binds NHERF1 and GPRASP1 (PubMed:9560162). Interacts with CC ARRB1 and ARRB2. Interacts with SRC (PubMed:9924018). Interacts with CC USP20 and USP33 (PubMed:19424180, PubMed:23166351). Interacts with VHL; CC the interaction, which is increased on hydroxylation of ADRB2, CC ubiquitinates ADRB2 leading to its degradation. Interacts with EGLN3; CC the interaction hydroxylates ADRB2 facilitating VHL-E3 ligase-mediated CC ubiquitination. Interacts (via PDZ-binding motif) with SNX27 (via PDZ CC domain); the interaction is required when endocytosed to prevent CC degradation in lysosomes and promote recycling to the plasma membrane. CC Interacts with CNIH4 (PubMed:24405750). Interacts with ARRDC3 CC (PubMed:20559325, PubMed:25220262). Interacts with NEDD4 CC (PubMed:23166351). Interacts with MARCHF2 (PubMed:23166351). CC {ECO:0000269|PubMed:10499588, ECO:0000269|PubMed:12142540, CC ECO:0000269|PubMed:17952055, ECO:0000269|PubMed:17962520, CC ECO:0000269|PubMed:18547522, ECO:0000269|PubMed:19424180, CC ECO:0000269|PubMed:19584355, ECO:0000269|PubMed:20559325, CC ECO:0000269|PubMed:20733053, ECO:0000269|PubMed:21602791, CC ECO:0000269|PubMed:23166351, ECO:0000269|PubMed:24405750, CC ECO:0000269|PubMed:25220262, ECO:0000269|PubMed:7822302, CC ECO:0000269|PubMed:9388255, ECO:0000269|PubMed:9560162, CC ECO:0000269|PubMed:9924018}. CC -!- INTERACTION: CC P07550; P30542: ADORA1; NbExp=5; IntAct=EBI-491169, EBI-2903663; CC P07550; P07550: ADRB2; NbExp=4; IntAct=EBI-491169, EBI-491169; CC P07550; P32121: ARRB2; NbExp=3; IntAct=EBI-491169, EBI-714559; CC P07550; Q96B67: ARRDC3; NbExp=6; IntAct=EBI-491169, EBI-2875665; CC P07550; Q9UII2: ATP5IF1; NbExp=3; IntAct=EBI-491169, EBI-718459; CC P07550; Q9ULD4-2: BRPF3; NbExp=3; IntAct=EBI-491169, EBI-23662416; CC P07550; Q9NSI6-4: BRWD1; NbExp=3; IntAct=EBI-491169, EBI-10693038; CC P07550; Q5M9N0-2: CCDC158; NbExp=3; IntAct=EBI-491169, EBI-21796846; CC P07550; A0AVK6: E2F8; NbExp=3; IntAct=EBI-491169, EBI-7779316; CC P07550; Q658K8: EEF1DP3; NbExp=3; IntAct=EBI-491169, EBI-10248874; CC P07550; O00472: ELL2; NbExp=3; IntAct=EBI-491169, EBI-395274; CC P07550; Q15910-2: EZH2; NbExp=3; IntAct=EBI-491169, EBI-10699473; CC P07550; Q15486: GUSBP1; NbExp=3; IntAct=EBI-491169, EBI-712457; CC P07550; P61978: HNRNPK; NbExp=2; IntAct=EBI-491169, EBI-304185; CC P07550; Q5TCQ9: MAGI3; NbExp=9; IntAct=EBI-491169, EBI-310506; CC P07550; Q99685: MGLL; NbExp=2; IntAct=EBI-491169, EBI-721306; CC P07550; O14745: NHERF1; NbExp=6; IntAct=EBI-491169, EBI-349787; CC P07550; Q9NR21-5: PARP11; NbExp=3; IntAct=EBI-491169, EBI-17159452; CC P07550; Q8WVD3: RNF138; NbExp=3; IntAct=EBI-491169, EBI-749039; CC P07550; Q9H0X6: RNF208; NbExp=3; IntAct=EBI-491169, EBI-751555; CC P07550; Q13573: SNW1; NbExp=3; IntAct=EBI-491169, EBI-632715; CC P07550; P12931: SRC; NbExp=3; IntAct=EBI-491169, EBI-621482; CC P07550; Q5T0J7-2: TEX35; NbExp=3; IntAct=EBI-491169, EBI-12833746; CC P07550; Q8N0U2: TMEM61; NbExp=3; IntAct=EBI-491169, EBI-25830583; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19584355, CC ECO:0000269|PubMed:20559325, ECO:0000269|PubMed:23166351, CC ECO:0000269|PubMed:25220262, ECO:0000269|PubMed:2831218, CC ECO:0000269|PubMed:7915137}; Multi-pass membrane protein CC {ECO:0000269|PubMed:19584355, ECO:0000269|PubMed:24056936}. Golgi CC apparatus {ECO:0000269|PubMed:27481942}. Note=Colocalizes with VHL at CC the cell membrane (PubMed:19584355). Activated receptors are CC internalized into endosomes prior to their degradation in lysosomes CC (PubMed:20559325). Activated receptors are also detected within the CC Golgi apparatus (PubMed:27481942). {ECO:0000269|PubMed:19584355, CC ECO:0000269|PubMed:20559325, ECO:0000269|PubMed:27481942}. CC -!- PTM: Palmitoylated (PubMed:11146000, PubMed:17962520, PubMed:18547522, CC PubMed:2540197, PubMed:27481942). Mainly palmitoylated at Cys-341 CC (PubMed:17962520, PubMed:18547522, PubMed:2540197). Palmitoylation may CC reduce accessibility of phosphorylation sites by anchoring the receptor CC to the plasma membrane. Agonist stimulation promotes depalmitoylation CC and further allows Ser-345 and Ser-346 phosphorylation CC (PubMed:11146000). Also undergoes transient, ligand-induced CC palmitoylation at Cys-265 probably by ZDHHC9, ZDHHC14 and ZDHHC18 CC within the Golgi (PubMed:27481942). Palmitoylation at Cys-265 requires CC phosphorylation by PKA and receptor internalization and stabilizes the CC receptor (PubMed:27481942). Could be depalmitoylated by LYPLA1 at the CC plasma membrane (PubMed:27481942). {ECO:0000269|PubMed:11146000, CC ECO:0000269|PubMed:17962520, ECO:0000269|PubMed:18547522, CC ECO:0000269|PubMed:2540197, ECO:0000269|PubMed:27481942}. CC -!- PTM: Phosphorylated by PKA and BARK/GRK2 upon agonist stimulation, CC which mediates homologous desensitization of the receptor. PKA-mediated CC phosphorylation seems to facilitate phosphorylation by BARK/GRK2 CC (PubMed:11146000). Distinct temporal phosphorylation on Ser-355 and CC Ser-356 by BARK/GRK2 plays a critical role for dictating receptor CC cellular events and signaling properties induced by Epi or NE in CC cardiomyocytes (By similarity). {ECO:0000250|UniProtKB:P18762, CC ECO:0000269|PubMed:11146000}. CC -!- PTM: Phosphorylation of Tyr-141 is induced by insulin and leads to CC supersensitization of the receptor. {ECO:0000269|PubMed:8521811}. CC -!- PTM: Polyubiquitinated (PubMed:23166351). Agonist-induced CC ubiquitination leads to sort internalized receptors to the lysosomes CC for degradation (PubMed:19424180, PubMed:20559325, PubMed:23166351). CC Deubiquitination by USP20 and USP33, leads to ADRB2 recycling and CC resensitization after prolonged agonist stimulation. USP20 and USP33 CC are constitutively associated and are dissociated immediately after CC agonist stimulation. Ubiquitination by the VHL-E3 ligase complex is CC oxygen-dependent. {ECO:0000269|PubMed:19424180, CC ECO:0000269|PubMed:20559325, ECO:0000269|PubMed:23166351}. CC -!- PTM: Hydroxylation by EGLN3 occurs only under normoxia and increases CC the interaction with VHL and the subsequent ubiquitination and CC degradation of ADRB2. {ECO:0000269|PubMed:19424180, CC ECO:0000269|PubMed:19584355}. CC -!- POLYMORPHISM: The Gly-16 allele is overrepresented in individuals CC affected by nocturnal asthma as compared to controls, and appears to be CC an important genetic factor in the expression of this asthmatic CC phenotype. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC Adrenergic receptor subfamily. ADRB2 sub-subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. CC -!- SEQUENCE CAUTION: CC Sequence=BAD96745.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) 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_000015.2; NM_000024.6. 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 PDB; 4QKX; X-ray; 3.30 A; A=29-348. DR PDB; 5D5A; X-ray; 2.48 A; A=1-230, A=263-365. DR PDB; 5D5B; X-ray; 3.80 A; A=1-230, A=263-365. DR PDB; 5D6L; X-ray; 3.20 A; A=1-223, A=264-365. DR PDB; 5JQH; X-ray; 3.20 A; A/B=30-348. DR PDB; 5X7D; X-ray; 2.70 A; A=1-230, A=264-365. DR PDB; 6E67; X-ray; 3.70 A; A/B=1-232, A/B=268-365. DR PDB; 6KR8; NMR; -; A=25-350. DR PDB; 6MXT; X-ray; 2.96 A; A=29-365. DR PDB; 6N48; X-ray; 3.20 A; A=29-348. DR PDB; 6NI3; EM; 3.80 A; R=29-341. DR PDB; 6OBA; X-ray; 3.10 A; A=1-230, A=264-365. DR PDB; 6PRZ; X-ray; 2.80 A; A=1-230, A=264-348. DR PDB; 6PS0; X-ray; 3.40 A; A=1-230, A=264-348. DR PDB; 6PS1; X-ray; 3.20 A; A=1-230, A=264-348. DR PDB; 6PS2; X-ray; 2.40 A; A=1-230, A=264-348. DR PDB; 6PS3; X-ray; 2.50 A; A=1-230, A=264-348. DR PDB; 6PS4; X-ray; 2.60 A; A=1-230, A=264-348. DR PDB; 6PS5; X-ray; 2.90 A; A=1-230, A=264-348. DR PDB; 6PS6; X-ray; 2.70 A; A=1-230, A=264-348. DR PDB; 7BZ2; EM; 3.82 A; R=1-348. DR PDB; 7DHI; EM; 3.26 A; R=1-348. DR PDB; 7DHR; EM; 3.80 A; R=1-348. DR PDB; 7XK9; X-ray; 3.40 A; A=29-348. DR PDB; 7XKA; X-ray; 3.10 A; A=29-348. DR PDB; 8GDZ; EM; 3.50 A; R=1-413. DR PDB; 8GE1; EM; 3.40 A; R=1-413. DR PDB; 8GE2; EM; 3.30 A; R=1-413. DR PDB; 8GE3; EM; 3.30 A; R=1-413. DR PDB; 8GE4; EM; 3.30 A; R=1-413. DR PDB; 8GE5; EM; 3.20 A; R=1-413. DR PDB; 8GE6; EM; 3.40 A; R=1-413. DR PDB; 8GE7; EM; 3.40 A; R=1-413. DR PDB; 8GE8; EM; 3.40 A; R=1-413. DR PDB; 8GE9; EM; 3.50 A; R=1-413. DR PDB; 8GEA; EM; 3.50 A; R=1-413. DR PDB; 8GEB; EM; 3.60 A; R=1-413. DR PDB; 8GEC; EM; 3.50 A; R=1-413. DR PDB; 8GED; EM; 3.50 A; R=1-413. DR PDB; 8GEE; EM; 3.70 A; R=1-413. DR PDB; 8GEF; EM; 3.80 A; R=1-413. DR PDB; 8GEG; EM; 3.80 A; R=1-413. DR PDB; 8GEH; EM; 4.00 A; R=1-413. DR PDB; 8GEI; EM; 4.10 A; R=1-413. DR PDB; 8GEJ; EM; 4.20 A; R=1-413. DR PDB; 8GFV; EM; 3.10 A; R=1-413. DR PDB; 8GFW; EM; 3.00 A; R=1-413. DR PDB; 8GFX; EM; 3.00 A; R=1-413. DR PDB; 8GFY; EM; 3.00 A; R=1-413. DR PDB; 8GFZ; EM; 3.00 A; R=1-413. DR PDB; 8GG0; EM; 2.90 A; R=1-413. DR PDB; 8GG1; EM; 3.00 A; R=1-413. DR PDB; 8GG2; EM; 3.00 A; R=1-413. DR PDB; 8GG3; EM; 3.10 A; R=1-413. DR PDB; 8GG4; EM; 3.20 A; R=1-413. DR PDB; 8GG5; EM; 3.20 A; R=1-413. DR PDB; 8GG6; EM; 3.30 A; R=1-413. DR PDB; 8GG7; EM; 3.30 A; R=1-413. DR PDB; 8GG8; EM; 3.30 A; R=1-413. DR PDB; 8GG9; EM; 3.40 A; R=1-413. DR PDB; 8GGA; EM; 3.50 A; R=1-413. DR PDB; 8GGB; EM; 3.50 A; R=1-413. DR PDB; 8GGC; EM; 3.40 A; R=1-413. DR PDB; 8GGE; EM; 3.50 A; R=1-413. DR PDB; 8GGF; EM; 3.60 A; R=1-413. DR PDB; 8GGI; EM; 3.50 A; R=1-413. DR PDB; 8GGJ; EM; 3.50 A; R=1-413. DR PDB; 8GGK; EM; 3.30 A; R=1-413. DR PDB; 8GGL; EM; 3.20 A; R=1-413. DR PDB; 8GGM; EM; 3.20 A; R=1-413. DR PDB; 8GGN; EM; 3.30 A; R=1-413. DR PDB; 8GGO; EM; 3.20 A; R=1-413. DR PDB; 8GGP; EM; 3.20 A; R=1-413. DR PDB; 8GGQ; EM; 3.40 A; R=1-413. DR PDB; 8GGR; EM; 3.40 A; R=1-413. DR PDB; 8GGS; EM; 3.50 A; R=1-413. DR PDB; 8GGT; EM; 3.50 A; R=1-413. DR PDB; 8GGU; EM; 3.40 A; R=1-413. DR PDB; 8GGV; EM; 3.50 A; R=1-413. DR PDB; 8GGW; EM; 3.60 A; R=1-413. DR PDB; 8GGX; EM; 3.60 A; R=1-413. DR PDB; 8GGY; EM; 3.90 A; R=1-413. DR PDB; 8GGZ; EM; 3.90 A; R=1-413. DR PDB; 8GH0; EM; 4.00 A; R=1-413. DR PDB; 8GH1; EM; 4.10 A; R=1-413. DR PDB; 8JJ8; EM; 3.20 A; F=29-230, F=263-340. DR PDB; 8JJL; EM; 3.20 A; A=29-230, A=263-340. DR PDB; 8JJO; EM; 3.40 A; F=29-340. DR PDB; 8UHB; EM; 3.35 A; A=1-30. DR PDB; 8UNL; EM; 3.30 A; R=1-413. DR PDB; 8UNM; EM; 3.40 A; R=1-413. DR PDB; 8UNN; EM; 3.40 A; R=1-413. DR PDB; 8UNO; EM; 3.30 A; R=1-413. DR PDB; 8UNP; EM; 3.30 A; R=1-413. DR PDB; 8UNQ; EM; 3.30 A; R=1-413. DR PDB; 8UNR; EM; 3.40 A; R=1-413. DR PDB; 8UNS; EM; 3.40 A; R=1-413. DR PDB; 8UNT; EM; 3.40 A; R=1-413. DR PDB; 8UNU; EM; 3.50 A; R=1-413. DR PDB; 8UNV; EM; 3.30 A; R=1-413. DR PDB; 8UNW; EM; 3.40 A; R=1-413. DR PDB; 8UNX; EM; 3.60 A; R=1-413. DR PDB; 8UNY; EM; 3.60 A; R=1-413. DR PDB; 8UNZ; EM; 3.80 A; R=1-413. DR PDB; 8UO0; EM; 3.50 A; R=1-413. DR PDB; 8UO1; EM; 3.60 A; R=1-413. DR PDB; 8UO2; EM; 3.60 A; R=1-413. DR PDB; 8UO3; EM; 3.50 A; R=1-413. DR PDB; 8UO4; EM; 4.00 A; R=1-413. DR PDB; 8W1V; X-ray; 3.00 A; A/B=1-365. DR PDB; 8ZBE; EM; 3.24 A; A=1-24, A=385-400. DR PDB; 8ZCJ; EM; 3.09 A; G=1-24, G=385-400. DR PDB; 8ZWF; EM; 3.00 A; A=1-30. DR PDB; 9BUY; EM; 2.90 A; R=1-413. DR PDB; 9CHU; EM; 3.49 A; A=29-230, A=263-336. DR PDB; 9CHV; EM; 3.95 A; A=29-230, A=263-354. DR PDB; 9CHX; EM; 3.50 A; A=29-230, A=263-354. 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 PDBsum; 4QKX; -. DR PDBsum; 5D5A; -. DR PDBsum; 5D5B; -. DR PDBsum; 5D6L; -. DR PDBsum; 5JQH; -. DR PDBsum; 5X7D; -. DR PDBsum; 6E67; -. DR PDBsum; 6KR8; -. DR PDBsum; 6MXT; -. DR PDBsum; 6N48; -. DR PDBsum; 6NI3; -. DR PDBsum; 6OBA; -. DR PDBsum; 6PRZ; -. DR PDBsum; 6PS0; -. DR PDBsum; 6PS1; -. DR PDBsum; 6PS2; -. DR PDBsum; 6PS3; -. DR PDBsum; 6PS4; -. DR PDBsum; 6PS5; -. DR PDBsum; 6PS6; -. DR PDBsum; 7BZ2; -. DR PDBsum; 7DHI; -. DR PDBsum; 7DHR; -. DR PDBsum; 7XK9; -. DR PDBsum; 7XKA; -. DR PDBsum; 8GDZ; -. DR PDBsum; 8GE1; -. DR PDBsum; 8GE2; -. DR PDBsum; 8GE3; -. DR PDBsum; 8GE4; -. DR PDBsum; 8GE5; -. DR PDBsum; 8GE6; -. DR PDBsum; 8GE7; -. DR PDBsum; 8GE8; -. DR PDBsum; 8GE9; -. DR PDBsum; 8GEA; -. DR PDBsum; 8GEB; -. DR PDBsum; 8GEC; -. DR PDBsum; 8GED; -. DR PDBsum; 8GEE; -. DR PDBsum; 8GEF; -. DR PDBsum; 8GEG; -. DR PDBsum; 8GEH; -. DR PDBsum; 8GEI; -. DR PDBsum; 8GEJ; -. DR PDBsum; 8GFV; -. DR PDBsum; 8GFW; -. DR PDBsum; 8GFX; -. DR PDBsum; 8GFY; -. DR PDBsum; 8GFZ; -. DR PDBsum; 8GG0; -. DR PDBsum; 8GG1; -. DR PDBsum; 8GG2; -. DR PDBsum; 8GG3; -. DR PDBsum; 8GG4; -. DR PDBsum; 8GG5; -. DR PDBsum; 8GG6; -. DR PDBsum; 8GG7; -. DR PDBsum; 8GG8; -. DR PDBsum; 8GG9; -. DR PDBsum; 8GGA; -. DR PDBsum; 8GGB; -. DR PDBsum; 8GGC; -. DR PDBsum; 8GGE; -. DR PDBsum; 8GGF; -. DR PDBsum; 8GGI; -. DR PDBsum; 8GGJ; -. DR PDBsum; 8GGK; -. DR PDBsum; 8GGL; -. DR PDBsum; 8GGM; -. DR PDBsum; 8GGN; -. DR PDBsum; 8GGO; -. DR PDBsum; 8GGP; -. DR PDBsum; 8GGQ; -. DR PDBsum; 8GGR; -. DR PDBsum; 8GGS; -. DR PDBsum; 8GGT; -. DR PDBsum; 8GGU; -. DR PDBsum; 8GGV; -. DR PDBsum; 8GGW; -. DR PDBsum; 8GGX; -. DR PDBsum; 8GGY; -. DR PDBsum; 8GGZ; -. DR PDBsum; 8GH0; -. DR PDBsum; 8GH1; -. DR PDBsum; 8JJ8; -. DR PDBsum; 8JJL; -. DR PDBsum; 8JJO; -. DR PDBsum; 8UHB; -. DR PDBsum; 8UNL; -. DR PDBsum; 8UNM; -. DR PDBsum; 8UNN; -. DR PDBsum; 8UNO; -. DR PDBsum; 8UNP; -. DR PDBsum; 8UNQ; -. DR PDBsum; 8UNR; -. DR PDBsum; 8UNS; -. DR PDBsum; 8UNT; -. DR PDBsum; 8UNU; -. DR PDBsum; 8UNV; -. DR PDBsum; 8UNW; -. DR PDBsum; 8UNX; -. DR PDBsum; 8UNY; -. DR PDBsum; 8UNZ; -. DR PDBsum; 8UO0; -. DR PDBsum; 8UO1; -. DR PDBsum; 8UO2; -. DR PDBsum; 8UO3; -. DR PDBsum; 8UO4; -. DR PDBsum; 8W1V; -. DR PDBsum; 8ZBE; -. DR PDBsum; 8ZCJ; -. DR PDBsum; 8ZWF; -. DR PDBsum; 9BUY; -. DR PDBsum; 9CHU; -. DR PDBsum; 9CHV; -. DR PDBsum; 9CHX; -. DR AlphaFoldDB; P07550; -. DR EMDB; EMD-29951; -. DR EMDB; EMD-29952; -. DR EMDB; EMD-29953; -. DR EMDB; EMD-29954; -. DR EMDB; EMD-29955; -. DR EMDB; EMD-29956; -. DR EMDB; EMD-29958; -. DR EMDB; EMD-29959; -. DR EMDB; EMD-29960; -. DR EMDB; EMD-29961; -. DR EMDB; EMD-29962; -. DR EMDB; EMD-29964; -. DR EMDB; EMD-29965; -. DR EMDB; EMD-29966; -. DR EMDB; EMD-29967; -. DR EMDB; EMD-29968; -. DR EMDB; EMD-29969; -. DR EMDB; EMD-29970; -. DR EMDB; EMD-29971; -. DR EMDB; EMD-29972; -. DR EMDB; EMD-29985; -. DR EMDB; EMD-29986; -. DR EMDB; EMD-29987; -. DR EMDB; EMD-29988; -. DR EMDB; EMD-29989; -. DR EMDB; EMD-29990; -. DR EMDB; EMD-29991; -. DR EMDB; EMD-29992; -. DR EMDB; EMD-29993; -. DR EMDB; EMD-29994; -. DR EMDB; EMD-29995; -. DR EMDB; EMD-29996; -. DR EMDB; EMD-29997; -. DR EMDB; EMD-29998; -. DR EMDB; EMD-29999; -. DR EMDB; EMD-30249; -. DR EMDB; EMD-30681; -. DR EMDB; EMD-30682; -. DR EMDB; EMD-36342; -. DR EMDB; EMD-36360; -. DR EMDB; EMD-36361; -. DR EMDB; EMD-40000; -. DR EMDB; EMD-40001; -. DR EMDB; EMD-40002; -. DR EMDB; EMD-40004; -. DR EMDB; EMD-40005; -. DR EMDB; EMD-40009; -. DR EMDB; EMD-40010; -. DR EMDB; EMD-40011; -. DR EMDB; EMD-40012; -. DR EMDB; EMD-40013; -. DR EMDB; EMD-40014; -. DR EMDB; EMD-40015; -. DR EMDB; EMD-40016; -. DR EMDB; EMD-40017; -. DR EMDB; EMD-40018; -. DR EMDB; EMD-40019; -. DR EMDB; EMD-40020; -. DR EMDB; EMD-40021; -. DR EMDB; EMD-40022; -. DR EMDB; EMD-40023; -. DR EMDB; EMD-40024; -. DR EMDB; EMD-40025; -. DR EMDB; EMD-40026; -. DR EMDB; EMD-40027; -. DR EMDB; EMD-40028; -. DR EMDB; EMD-40096; -. DR EMDB; EMD-40097; -. DR EMDB; EMD-40098; -. DR EMDB; EMD-40099; -. DR EMDB; EMD-40100; -. DR EMDB; EMD-40101; -. DR EMDB; EMD-40102; -. DR EMDB; EMD-40103; -. DR EMDB; EMD-40104; -. DR EMDB; EMD-40105; -. DR EMDB; EMD-40106; -. DR EMDB; EMD-40107; -. DR EMDB; EMD-40108; -. DR EMDB; EMD-40109; -. DR EMDB; EMD-40110; -. DR EMDB; EMD-40111; -. DR EMDB; EMD-40112; -. DR EMDB; EMD-40113; -. DR EMDB; EMD-40114; -. DR EMDB; EMD-40115; -. DR EMDB; EMD-40116; -. DR EMDB; EMD-40117; -. DR EMDB; EMD-40118; -. DR EMDB; EMD-40119; -. DR EMDB; EMD-40121; -. DR EMDB; EMD-40122; -. DR EMDB; EMD-40123; -. DR EMDB; EMD-40124; -. DR EMDB; EMD-40125; -. DR EMDB; EMD-40126; -. DR EMDB; EMD-40127; -. DR EMDB; EMD-40128; -. DR EMDB; EMD-40129; -. DR EMDB; EMD-40130; -. DR EMDB; EMD-40131; -. DR EMDB; EMD-40132; -. DR EMDB; EMD-40133; -. DR EMDB; EMD-40134; -. DR EMDB; EMD-40135; -. DR EMDB; EMD-40136; -. DR EMDB; EMD-40137; -. DR EMDB; EMD-40138; -. DR EMDB; EMD-40139; -. DR EMDB; EMD-40140; -. DR EMDB; EMD-40141; -. DR EMDB; EMD-40142; -. DR EMDB; EMD-40143; -. DR EMDB; EMD-40144; -. DR EMDB; EMD-40145; -. DR EMDB; EMD-40146; -. DR EMDB; EMD-40147; -. DR EMDB; EMD-40148; -. DR EMDB; EMD-40149; -. DR EMDB; EMD-40150; -. DR EMDB; EMD-40152; -. DR EMDB; EMD-40153; -. DR EMDB; EMD-40154; -. DR EMDB; EMD-40155; -. DR EMDB; EMD-40157; -. DR EMDB; EMD-40158; -. DR EMDB; EMD-40159; -. DR EMDB; EMD-40160; -. DR EMDB; EMD-40161; -. DR EMDB; EMD-40163; -. DR EMDB; EMD-40164; -. DR EMDB; EMD-40165; -. DR EMDB; EMD-40166; -. DR EMDB; EMD-40167; -. DR EMDB; EMD-40170; -. DR EMDB; EMD-40171; -. DR EMDB; EMD-40172; -. DR EMDB; EMD-40173; -. DR EMDB; EMD-40174; -. DR EMDB; EMD-40175; -. DR EMDB; EMD-40176; -. DR EMDB; EMD-42408; -. DR EMDB; EMD-42409; -. DR EMDB; EMD-42410; -. DR EMDB; EMD-42411; -. DR EMDB; EMD-42412; -. DR EMDB; EMD-42413; -. DR EMDB; EMD-42414; -. DR EMDB; EMD-42415; -. DR EMDB; EMD-42416; -. DR EMDB; EMD-42417; -. DR EMDB; EMD-42418; -. DR EMDB; EMD-42419; -. DR EMDB; EMD-42420; -. DR EMDB; EMD-42421; -. DR EMDB; EMD-42422; -. DR EMDB; EMD-42423; -. DR EMDB; EMD-42424; -. DR EMDB; EMD-42425; -. DR EMDB; EMD-42426; -. DR EMDB; EMD-42427; -. DR EMDB; EMD-44925; -. DR EMDB; EMD-45602; -. DR EMDB; EMD-45603; -. DR EMDB; EMD-45604; -. DR EMDB; EMD-63971; -. DR EMDB; EMD-9376; -. DR SMR; P07550; -. DR BioGRID; 106663; 326. DR CORUM; P07550; -. DR DIP; DIP-33948N; -. DR ELM; P07550; -. DR FunCoup; P07550; 1168. DR IntAct; P07550; 114. DR MINT; P07550; -. DR STRING; 9606.ENSP00000305372; -. DR BindingDB; P07550; -. DR ChEMBL; CHEMBL210; -. DR DrugBank; DB07543; (S)-carazolol. DR DrugBank; DB12100; Abediterol. DR DrugBank; DB01193; Acebutolol. DR DrugBank; DB01001; Albuterol. DR DrugBank; DB00866; Alprenolol. DR DrugBank; DB01118; Amiodarone. DR DrugBank; DB00182; Amphetamine. DR DrugBank; DB18759; APD-209. DR DrugBank; DB01102; Arbutamine. DR DrugBank; DB01274; Arformoterol. DR DrugBank; DB01238; Aripiprazole. DR DrugBank; DB09204; Arotinolol. DR DrugBank; DB06216; Asenapine. DR DrugBank; DB00335; Atenolol. DR DrugBank; DB01408; Bambuterol. DR DrugBank; DB12526; Batefenterol. DR DrugBank; DB05590; Bedoradrine. DR DrugBank; DB09013; Befunolol. DR DrugBank; DB00195; Betaxolol. DR DrugBank; DB00217; Bethanidine. DR DrugBank; DB01295; Bevantolol. DR DrugBank; DB00612; Bisoprolol. DR DrugBank; DB00901; Bitolterol. DR DrugBank; DB08807; Bopindolol. DR DrugBank; DB12752; Bucindolol. DR DrugBank; DB06726; Bufuralol. DR DrugBank; DB08808; Bupranolol. DR DrugBank; DB00248; Cabergoline. DR DrugBank; DB15784; Carmoterol. DR DrugBank; DB00521; Carteolol. DR DrugBank; DB01136; Carvedilol. DR DrugBank; DB04846; Celiprolol. DR DrugBank; DB01407; Clenbuterol. DR DrugBank; DB00785; Cryptenamine. DR DrugBank; DB01151; Desipramine. DR DrugBank; DB12803; Dichloroisoproterenol. DR DrugBank; DB11273; Dihydroergocornine. DR DrugBank; DB13345; Dihydroergocristine. DR DrugBank; DB00449; Dipivefrin. DR DrugBank; DB11278; DL-Methylephedrine. DR DrugBank; DB00841; Dobutamine. DR DrugBank; DB09273; Doxofylline. DR DrugBank; DB06262; Droxidopa. DR DrugBank; DB01363; Ephedra sinica root. DR DrugBank; DB01364; Ephedrine. DR DrugBank; DB00668; Epinephrine. DR DrugBank; DB01049; Ergoloid mesylate. DR DrugBank; DB11587; Etafedrine. DR DrugBank; DB01288; Fenoterol. DR DrugBank; DB00983; Formoterol. DR DrugBank; DB04946; Iloperidone. DR DrugBank; DB05039; Indacaterol. DR DrugBank; DB00221; Isoetharine. DR DrugBank; DB01064; Isoprenaline. DR DrugBank; DB00598; Labetalol. DR DrugBank; DB01210; Levobunolol. DR DrugBank; DB13139; Levosalbutamol. DR DrugBank; DB01365; Mephentermine. DR DrugBank; DB13624; Methoxyphenamine. DR DrugBank; DB01214; Metipranolol. DR DrugBank; DB00264; Metoprolol. DR DrugBank; DB01203; Nadolol. DR DrugBank; DB05849; NCX 950. DR DrugBank; DB04861; Nebivolol. DR DrugBank; DB00368; Norepinephrine. DR DrugBank; DB00540; Nortriptyline. DR DrugBank; DB00334; Olanzapine. DR DrugBank; DB09080; Olodaterol. DR DrugBank; DB00816; Orciprenaline. DR DrugBank; DB01580; Oxprenolol. DR DrugBank; DB00715; Paroxetine. DR DrugBank; DB01359; Penbutolol. DR DrugBank; DB11871; PF-00610355. DR DrugBank; DB00925; Phenoxybenzamine. DR DrugBank; DB00397; Phenylpropanolamine. DR DrugBank; DB00960; Pindolol. DR DrugBank; DB01291; Pirbuterol. DR DrugBank; DB01366; Procaterol. DR DrugBank; DB01182; Propafenone. DR DrugBank; DB00571; Propranolol. DR DrugBank; DB06814; Protokylol. DR DrugBank; DB00852; Pseudoephedrine. DR DrugBank; DB01917; Putrescine. DR DrugBank; DB06483; PW2101. DR DrugBank; DB11124; Racepinephrine. DR DrugBank; DB00867; Ritodrine. DR DrugBank; DB00938; Salmeterol. DR DrugBank; DB00489; Sotalol. DR DrugBank; DB03566; Spermidine. DR DrugBank; DB00127; Spermine. DR DrugBank; DB00871; Terbutaline. DR DrugBank; DB00373; Timolol. DR DrugBank; DB00726; Trimipramine. DR DrugBank; DB12248; Tulobuterol. DR DrugBank; DB09082; Vilanterol. DR DrugBank; DB09185; Viloxazine. DR DrugCentral; P07550; -. DR GuidetoPHARMACOLOGY; 29; -. DR MoonDB; P07550; Predicted. DR TCDB; 9.A.14.3.5; the g-protein-coupled receptor (gpcr) family. DR GlyCosmos; P07550; 2 sites, No reported glycans. DR GlyGen; P07550; 4 sites, 1 O-linked glycan (1 site). DR iPTMnet; P07550; -. DR PhosphoSitePlus; P07550; -. DR SwissPalm; P07550; -. DR BioMuta; ADRB2; -. DR DMDM; 296439450; -. DR jPOST; P07550; -. DR MassIVE; P07550; -. DR PaxDb; 9606-ENSP00000305372; -. DR PeptideAtlas; P07550; -. DR ProteomicsDB; 52013; -. DR ABCD; P07550; 44 sequenced antibodies. DR Antibodypedia; 15959; 1153 antibodies from 44 providers. DR DNASU; 154; -. DR Ensembl; ENST00000305988.6; ENSP00000305372.4; ENSG00000169252.6. DR GeneID; 154; -. DR KEGG; hsa:154; -. DR MANE-Select; ENST00000305988.6; ENSP00000305372.4; NM_000024.6; NP_000015.2. DR AGR; HGNC:286; -. DR ClinPGx; PA39; -. DR CTD; 154; -. DR DisGeNET; 154; -. DR GeneCards; ADRB2; -. DR HGNC; HGNC:286; ADRB2. DR HPA; ENSG00000169252; Low tissue specificity. DR MalaCards; ADRB2; -. DR MIM; 109690; gene+phenotype. DR OpenTargets; ENSG00000169252; -. DR VEuPathDB; HostDB:ENSG00000169252; -. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT00940000159538; -. DR HOGENOM; CLU_009579_11_0_1; -. DR InParanoid; P07550; -. DR OMA; CEFWISI; -. DR OrthoDB; 5975661at2759; -. DR PAN-GO; P07550; 6 GO annotations based on evolutionary models. DR PhylomeDB; P07550; -. DR PathwayCommons; P07550; -. DR Reactome; R-HSA-390696; Adrenoceptors. DR Reactome; R-HSA-418555; G alpha (s) signalling events. DR Reactome; R-HSA-5689880; Ub-specific processing proteases. DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis. DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis. DR SignaLink; P07550; -. DR SIGNOR; P07550; -. DR Agora; ENSG00000169252; -. DR BioGRID-ORCS; 154; 10 hits in 1160 CRISPR screens. DR ChiTaRS; ADRB2; human. DR EvolutionaryTrace; P07550; -. DR GeneWiki; Beta-2_adrenergic_receptor; -. DR GenomeRNAi; 154; -. DR Pharos; P07550; Tclin. DR PRO; PR:P07550; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; P07550; protein. DR Bgee; ENSG00000169252; Expressed in cartilage tissue and 162 other cell types or tissues. DR ExpressionAtlas; P07550; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl. DR GO; GO:0036064; C:ciliary basal body; IDA:HPA. DR GO; GO:0005929; C:cilium; IDA:HPA. DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome. DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell. DR GO; GO:0005768; C:endosome; TAS:ProtInc. DR GO; GO:0010008; C:endosome membrane; TAS:Reactome. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0045171; C:intercellular bridge; IDA:HPA. DR GO; GO:0005764; C:lysosome; TAS:ProtInc. DR GO; GO:0016020; C:membrane; NAS:ARUK-UCL. DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA. DR GO; GO:0072686; C:mitotic spindle; IDA:HPA. DR GO; GO:0098992; C:neuronal dense core vesicle; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0043235; C:receptor complex; IDA:HGNC-UCL. DR GO; GO:0008179; F:adenylate cyclase binding; IEA:Ensembl. DR GO; GO:0001540; F:amyloid-beta binding; IDA:ARUK-UCL. DR GO; GO:0004941; F:beta2-adrenergic receptor activity; IDA:HGNC-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0051380; F:norepinephrine binding; IDA:HGNC-UCL. DR GO; GO:0015459; F:potassium channel regulator activity; IDA:BHF-UCL. DR GO; GO:0042803; F:protein homodimerization activity; IPI:HGNC-UCL. DR GO; GO:0044877; F:protein-containing complex binding; IPI:ARUK-UCL. DR GO; GO:0071880; P:adenylate cyclase-activating adrenergic receptor signaling pathway; IDA:HGNC-UCL. DR GO; GO:0071881; P:adenylate cyclase-inhibiting adrenergic receptor signaling pathway; ISS:UniProtKB. 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:CAFA. DR GO; GO:0098990; P:AMPA selective glutamate receptor signaling pathway; IGI:ARUK-UCL. 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:1904646; P:cellular response to amyloid-beta; IGI:ARUK-UCL. 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:0010667; P:negative regulation of cardiac muscle cell apoptotic process; ISS:UniProtKB. DR GO; GO:0045744; P:negative regulation of G protein-coupled receptor signaling pathway; IDA:HGNC-UCL. 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:0002025; P:norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure; IBA:GO_Central. DR GO; GO:1901098; P:positive regulation of autophagosome maturation; IDA:GO_Central. DR GO; GO:0030501; P:positive regulation of bone mineralization; IEA:Ensembl. DR GO; GO:0141163; P:positive regulation of cAMP/PKA signal transduction; IGI:ARUK-UCL. DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; ISS:UniProtKB. DR GO; GO:0106134; P:positive regulation of cardiac muscle cell contraction; ISS:UniProtKB. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:1904504; P:positive regulation of lipophagy; IDA:GO_Central. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:HGNC-UCL. DR GO; GO:0061885; P:positive regulation of mini excitatory postsynaptic potential; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0006898; P:receptor-mediated endocytosis; IDA:HGNC-UCL. DR GO; GO:0002028; P:regulation of sodium ion transport; IEA:Ensembl. DR GO; GO:0009409; P:response to cold; IEA:Ensembl. DR GO; GO:1990911; P:response to psychosocial stress; TAS:ARUK-UCL. DR GO; GO:0006939; P:smooth muscle contraction; IEA:Ensembl. DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl. DR CDD; cd15957; 7tmA_Beta2_AR; 1. DR DisProt; DP03692; -. DR FunFam; 1.20.1070.10:FF:000057; Beta-1 adrenergic receptor; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 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; ADRENERGIC RECEPTOR-RELATED G-PROTEIN COUPLED RECEPTOR; 1. DR PANTHER; PTHR24248:SF21; BETA-2 ADRENERGIC RECEPTOR; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR01103; ADRENERGICR. DR PRINTS; PR00562; ADRENRGCB2AR. DR PRINTS; PR00237; GPCRRHODOPSN. DR SMART; SM01381; 7TM_GPCR_Srsx; 1. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. 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; Disulfide bond; G-protein coupled receptor; KW Glycoprotein; Golgi apparatus; Hydroxylation; Lipoprotein; Membrane; KW Palmitate; Phosphoprotein; Proteomics identification; Receptor; KW Reference proteome; Transducer; Transmembrane; Transmembrane helix; KW Ubl conjugation. FT CHAIN 1..413 FT /note="Beta-2 adrenergic receptor" FT /id="PRO_0000069130" FT TOPO_DOM 1..29 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 30..56 FT /note="Helical; Name=1" FT /evidence="ECO:0000269|PubMed:24056936, FT ECO:0007744|PDB:4LDE" FT TOPO_DOM 57..70 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 71..96 FT /note="Helical; Name=2" FT /evidence="ECO:0000269|PubMed:24056936, FT ECO:0007744|PDB:4LDE" FT TOPO_DOM 97..103 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 104..129 FT /note="Helical; Name=3" FT /evidence="ECO:0000269|PubMed:24056936, FT ECO:0007744|PDB:4LDE" FT TOPO_DOM 130..149 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 150..171 FT /note="Helical; Name=4" FT /evidence="ECO:0000269|PubMed:24056936, FT ECO:0007744|PDB:4LDE" FT TOPO_DOM 172..197 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 198..220 FT /note="Helical; Name=5" FT /evidence="ECO:0000269|PubMed:24056936, FT ECO:0007744|PDB:4LDE" FT TOPO_DOM 221..274 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 275..298 FT /note="Helical; Name=6" FT /evidence="ECO:0000269|PubMed:24056936, FT ECO:0007744|PDB:4LDE" FT TOPO_DOM 299..304 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 305..326 FT /note="Helical; Name=7" FT /evidence="ECO:0000269|PubMed:24056936, FT ECO:0007744|PDB:4LDE" FT TOPO_DOM 327..413 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT REGION 392..413 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 410..413 FT /note="PDZ-binding" FT COMPBIAS 393..413 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 113 FT /ligand="(R)-adrenaline" FT /ligand_id="ChEBI:CHEBI:71406" FT /evidence="ECO:0000269|PubMed:24056936, FT ECO:0007744|PDB:4LDO" FT BINDING 113 FT /ligand="(S)-carazolol" FT /ligand_id="ChEBI:CHEBI:188146" FT /ligand_note="inverse agonist" FT /evidence="ECO:0000269|PubMed:17952055, FT ECO:0000269|PubMed:17962520, ECO:0007744|PDB:2RH1" FT BINDING 113 FT /ligand="(S)-timolol" FT /ligand_id="ChEBI:CHEBI:188157" FT /ligand_note="inverse agonist" FT /evidence="ECO:0000269|PubMed:18547522, FT ECO:0007744|PDB:3D4S" FT BINDING 118 FT /ligand="(S)-timolol" FT /ligand_id="ChEBI:CHEBI:188157" FT /ligand_note="inverse agonist" FT /evidence="ECO:0000269|PubMed:18547522, FT ECO:0007744|PDB:3D4S" FT BINDING 203 FT /ligand="(S)-carazolol" FT /ligand_id="ChEBI:CHEBI:188146" FT /ligand_note="inverse agonist" FT /evidence="ECO:0000269|PubMed:17952055, FT ECO:0000269|PubMed:17962520, ECO:0007744|PDB:2RH1" FT BINDING 293 FT /ligand="(R)-adrenaline" FT /ligand_id="ChEBI:CHEBI:71406" FT /evidence="ECO:0000269|PubMed:24056936, FT ECO:0007744|PDB:4LDO" FT BINDING 293 FT /ligand="(S)-timolol" FT /ligand_id="ChEBI:CHEBI:188157" FT /ligand_note="inverse agonist" FT /evidence="ECO:0000269|PubMed:18547522, FT ECO:0007744|PDB:3D4S" FT BINDING 312 FT /ligand="(R)-adrenaline" FT /ligand_id="ChEBI:CHEBI:71406" FT /evidence="ECO:0000269|PubMed:24056936, FT ECO:0007744|PDB:4LDO" FT BINDING 312 FT /ligand="(S)-carazolol" FT /ligand_id="ChEBI:CHEBI:188146" FT /ligand_note="inverse agonist" FT /evidence="ECO:0000269|PubMed:17952055, FT ECO:0000269|PubMed:17962520, ECO:0007744|PDB:2RH1" FT BINDING 312 FT /ligand="(S)-timolol" FT /ligand_id="ChEBI:CHEBI:188157" FT /ligand_note="inverse agonist" FT /evidence="ECO:0000269|PubMed:18547522, FT ECO:0007744|PDB:3D4S" FT BINDING 316 FT /ligand="(R)-adrenaline" FT /ligand_id="ChEBI:CHEBI:71406" FT /evidence="ECO:0000269|PubMed:24056936, FT ECO:0007744|PDB:4LDO" FT BINDING 316 FT /ligand="(S)-timolol" FT /ligand_id="ChEBI:CHEBI:188157" FT /ligand_note="inverse agonist" FT /evidence="ECO:0000269|PubMed:18547522, FT ECO:0007744|PDB:3D4S" FT MOD_RES 141 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:8521811" FT MOD_RES 246 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332" FT MOD_RES 261 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000255" FT MOD_RES 262 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000255" FT MOD_RES 345 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000269|PubMed:11146000" FT MOD_RES 346 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000269|PubMed:11146000" FT MOD_RES 355 FT /note="Phosphoserine; by BARK" FT /evidence="ECO:0000269|PubMed:18056263" FT MOD_RES 356 FT /note="Phosphoserine; by BARK" FT /evidence="ECO:0000269|PubMed:18056263" FT MOD_RES 382 FT /note="4-hydroxyproline" FT /evidence="ECO:0000269|PubMed:19584355" FT MOD_RES 395 FT /note="4-hydroxyproline" FT /evidence="ECO:0000269|PubMed:19584355" FT LIPID 265 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:27481942" FT LIPID 341 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:17962520, FT ECO:0000269|PubMed:18547522, ECO:0000269|PubMed:2540197, FT ECO:0000269|PubMed:27481942" FT CARBOHYD 6 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000305" FT CARBOHYD 15 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000305" FT DISULFID 106..191 FT /evidence="ECO:0000269|PubMed:24056936, FT ECO:0007744|PDB:4LDE, ECO:0007744|PDB:4LDL, FT ECO:0007744|PDB:4LDO" FT DISULFID 184..190 FT /evidence="ECO:0000269|PubMed:24056936, FT ECO:0007744|PDB:4LDE, ECO:0007744|PDB:4LDL, FT ECO:0007744|PDB:4LDO" FT VARIANT 15 FT /note="N -> S (in dbSNP:rs33973603)" FT /id="VAR_049373" FT VARIANT 16 FT /note="G -> R (in dbSNP:rs1042713)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:3025863, ECO:0000269|PubMed:3033609, FT ECO:0000269|PubMed:3034889, ECO:0000269|PubMed:7706471, FT ECO:0000269|PubMed:7915137, ECO:0000269|PubMed:8383511, FT ECO:0000269|Ref.8" FT /id="VAR_003452" FT VARIANT 27 FT /note="E -> Q (in dbSNP:rs1042714)" FT /evidence="ECO:0000269|PubMed:11246467, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:2823249, FT ECO:0000269|PubMed:3025863, ECO:0000269|PubMed:3026848, FT ECO:0000269|PubMed:3033609, ECO:0000269|PubMed:3034889, FT ECO:0000269|PubMed:7915137, ECO:0000269|PubMed:8383511, FT ECO:0000269|Ref.10, ECO:0000269|Ref.11, ECO:0000269|Ref.12, FT ECO:0000269|Ref.8" FT /id="VAR_003453" FT VARIANT 34 FT /note="V -> M (in dbSNP:rs990810566)" FT /evidence="ECO:0000269|PubMed:8383511" FT /id="VAR_003454" FT VARIANT 159 FT /note="I -> F" FT /evidence="ECO:0000269|PubMed:11246467" FT /id="VAR_009125" FT VARIANT 159 FT /note="I -> L" FT /evidence="ECO:0000269|PubMed:11246467" FT /id="VAR_009124" FT VARIANT 164 FT /note="T -> I (in dbSNP:rs1800888)" FT /evidence="ECO:0000269|PubMed:8383511" FT /id="VAR_003455" FT VARIANT 220 FT /note="S -> C (in dbSNP:rs3729943)" FT /evidence="ECO:0000269|Ref.11" FT /id="VAR_025101" FT VARIANT 375 FT /note="K -> R (in dbSNP:rs771585355)" FT /evidence="ECO:0000269|PubMed:11246467" FT /id="VAR_009394" FT MUTAGEN 79 FT /note="D->N: Affects binding of catecholamines, and FT produces an uncoupling between the receptor and stimulatory FT G proteins." FT /evidence="ECO:0000269|PubMed:2831218" FT MUTAGEN 141 FT /note="Y->F: Abolishes insulin-induced tyrosine FT phosphorylation and insulin-induced receptor FT supersensitization." FT /evidence="ECO:0000269|PubMed:8521811" FT MUTAGEN 174 FT /note="Y->W: Increased noradrenaline affinity." FT /evidence="ECO:0000269|PubMed:33093660" FT MUTAGEN 265 FT /note="C->A: Loss of ligand-induced palmitoylation." FT /evidence="ECO:0000269|PubMed:27481942" FT MUTAGEN 300 FT /note="D->R: Increased noradrenaline affinity." FT /evidence="ECO:0000269|PubMed:33093660" FT MUTAGEN 341 FT /note="C->A: Loss of basal palmitoylation." FT /evidence="ECO:0000269|PubMed:27481942" FT MUTAGEN 341 FT /note="C->G: Uncoupled receptor." FT /evidence="ECO:0000269|PubMed:2540197" FT MUTAGEN 345..346 FT /note="SS->AA: Delayed agonist-promoted desensitization." FT /evidence="ECO:0000269|PubMed:11146000" FT MUTAGEN 350 FT /note="Y->A: Does not affect insulin-induced tyrosine FT phosphorylation or insulin-induced receptor FT supersensitization." FT /evidence="ECO:0000269|PubMed:8521811" FT MUTAGEN 354 FT /note="Y->A: Does not affect insulin-induced tyrosine FT phosphorylation or insulin-induced receptor FT supersensitization." FT /evidence="ECO:0000269|PubMed:8521811" FT MUTAGEN 366 FT /note="Y->F: Does not affect insulin-induced tyrosine FT phosphorylation or insulin-induced receptor FT supersensitization." FT /evidence="ECO:0000269|PubMed:8521811" FT MUTAGEN 413 FT /note="L->A: Loss of interaction with NHERF1 after FT isoprenaline stimulation. Inhibition of SLC9A3 activity FT after isoprenaline stimulation. No change in adenylyl FT cyclase activation." FT /evidence="ECO:0000269|PubMed:9560162" FT CONFLICT 71 FT /note="F -> L (in Ref. 9; BAG35969)" FT /evidence="ECO:0000305" FT CONFLICT 216 FT /note="V -> A (in Ref. 8; AAN01267)" FT /evidence="ECO:0000305" FT CONFLICT 261 FT /note="S -> P (in Ref. 10; BAD96745)" FT /evidence="ECO:0000305" FT CONFLICT 402 FT /note="Q -> P (in Ref. 14; AAH12481)" FT /evidence="ECO:0000305" FT STRAND 25..27 FT /evidence="ECO:0007829|PDB:3P0G" FT HELIX 31..60 FT /evidence="ECO:0007829|PDB:2RH1" FT HELIX 62..64 FT /evidence="ECO:0007829|PDB:2RH1" FT HELIX 67..85 FT /evidence="ECO:0007829|PDB:2RH1" FT HELIX 87..96 FT /evidence="ECO:0007829|PDB:2RH1" FT HELIX 102..136 FT /evidence="ECO:0007829|PDB:2RH1" FT STRAND 137..139 FT /evidence="ECO:0007829|PDB:2RH1" FT STRAND 140..142 FT /evidence="ECO:0007829|PDB:6PS2" FT HELIX 147..170 FT /evidence="ECO:0007829|PDB:2RH1" FT TURN 171..174 FT /evidence="ECO:0007829|PDB:2RH1" FT HELIX 179..186 FT /evidence="ECO:0007829|PDB:2RH1" FT STRAND 187..189 FT /evidence="ECO:0007829|PDB:8GFV" FT HELIX 197..207 FT /evidence="ECO:0007829|PDB:2RH1" FT HELIX 209..229 FT /evidence="ECO:0007829|PDB:2RH1" FT TURN 238..240 FT /evidence="ECO:0007829|PDB:8GG0" FT HELIX 267..298 FT /evidence="ECO:0007829|PDB:2RH1" FT STRAND 299..303 FT /evidence="ECO:0007829|PDB:6PS4" FT HELIX 305..317 FT /evidence="ECO:0007829|PDB:2RH1" FT HELIX 318..320 FT /evidence="ECO:0007829|PDB:2RH1" FT HELIX 322..325 FT /evidence="ECO:0007829|PDB:2RH1" FT HELIX 326..328 FT /evidence="ECO:0007829|PDB:2RH1" FT HELIX 330..337 FT /evidence="ECO:0007829|PDB:8GG3" FT STRAND 338..343 FT /evidence="ECO:0007829|PDB:1GQ4" FT TURN 345..347 FT /evidence="ECO:0007829|PDB:2R4R" FT STRAND 355..357 FT /evidence="ECO:0007829|PDB:1GQ4" 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 //