ADRB2_HUMAN
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 03-AUG-2022, entry version 241.
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; 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 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 of
RT 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 protein
RT 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 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 [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 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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
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 [34] {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 [35] {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 [36] {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 [37]
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 [38]
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: Beta-adrenergic receptors mediate the catecholamine-induced
CC activation of adenylate cyclase through the action of G proteins. The
CC beta-2-adrenergic receptor binds epinephrine with an approximately 30-
CC fold greater affinity than it does norepinephrine.
CC {ECO:0000269|PubMed:2831218, ECO:0000269|PubMed:7915137}.
CC -!- SUBUNIT: Binds SLC9A3R1 and GPRASP1. Interacts with ARRB1 and ARRB2.
CC Interacts with SRC (PubMed:9924018). Interacts with USP20 and USP33
CC (PubMed:19424180, PubMed:23166351). Interacts with VHL; the
CC 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: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; 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; O14745: SLC9A3R1; NbExp=6; IntAct=EBI-491169, EBI-349787;
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}. Early endosome
CC {ECO:0000269|PubMed:20559325}. Golgi apparatus
CC {ECO:0000269|PubMed:27481942}. Note=Colocalizes with VHL at the cell
CC membrane (PubMed:19584355). Activated receptors are internalized into
CC endosomes prior to their degradation in lysosomes (PubMed:20559325).
CC Activated receptors are also detected within the Golgi apparatus
CC (PubMed:27481942). {ECO:0000269|PubMed:19584355,
CC ECO:0000269|PubMed:20559325, ECO:0000269|PubMed:27481942}.
CC -!- PTM: Palmitoylated (PubMed:2540197, PubMed:11146000, PubMed:27481942,
CC PubMed:17962520, PubMed:18547522). Mainly palmitoylated at Cys-341
CC (PubMed:2540197, PubMed:17962520, PubMed:18547522). 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 upon agonist stimulation, which
CC mediates homologous desensitization of the receptor. PKA-mediated
CC phosphorylation seems to facilitate phosphorylation by BARK.
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 -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/adrb2/";
CC ---------------------------------------------------------------------------
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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 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 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 AlphaFoldDB; P07550; -.
DR SMR; P07550; -.
DR BioGRID; 106663; 317.
DR CORUM; P07550; -.
DR DIP; DIP-33948N; -.
DR ELM; P07550; -.
DR IntAct; P07550; 107.
DR MINT; P07550; -.
DR STRING; 9606.ENSP00000305372; -.
DR BindingDB; P07550; -.
DR ChEMBL; CHEMBL210; -.
DR DrugBank; DB07543; (S)-carazolol.
DR DrugBank; DB01193; Acebutolol.
DR DrugBank; DB00866; Alprenolol.
DR DrugBank; DB01118; Amiodarone.
DR DrugBank; DB00182; Amphetamine.
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; 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; DB06726; Bufuralol.
DR DrugBank; DB08808; Bupranolol.
DR DrugBank; DB00248; Cabergoline.
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; 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; 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; 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; 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; DB11124; Racepinephrine.
DR DrugBank; DB00867; Ritodrine.
DR DrugBank; DB01001; Salbutamol.
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 DrugCentral; P07550; -.
DR GuidetoPHARMACOLOGY; 29; -.
DR MoonDB; P07550; Predicted.
DR TCDB; 9.A.14.3.5; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; P07550; 2 sites.
DR iPTMnet; P07550; -.
DR PhosphoSitePlus; P07550; -.
DR SwissPalm; P07550; -.
DR BioMuta; ADRB2; -.
DR DMDM; 296439450; -.
DR EPD; P07550; -.
DR jPOST; P07550; -.
DR MassIVE; P07550; -.
DR PaxDb; P07550; -.
DR PeptideAtlas; P07550; -.
DR PRIDE; P07550; -.
DR ProteomicsDB; 52013; -.
DR ABCD; P07550; 44 sequenced antibodies.
DR Antibodypedia; 15959; 1134 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 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 neXtProt; NX_P07550; -.
DR OpenTargets; ENSG00000169252; -.
DR PharmGKB; PA39; -.
DR VEuPathDB; HostDB:ENSG00000169252; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000159538; -.
DR HOGENOM; CLU_009579_11_0_1; -.
DR InParanoid; P07550; -.
DR OMA; RFHNQNN; -.
DR OrthoDB; 614199at2759; -.
DR PhylomeDB; P07550; -.
DR TreeFam; TF316350; -.
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 Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; P07550; -.
DR SIGNOR; P07550; -.
DR BioGRID-ORCS; 154; 7 hits in 1075 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 161 other tissues.
DR ExpressionAtlas; P07550; baseline and differential.
DR Genevisible; P07550; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
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:0005887; C:integral component of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005764; C:lysosome; TAS:ProtInc.
DR GO; GO:0016020; C:membrane; NAS:ARUK-UCL.
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:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
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; IDA:HGNC-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:ARUK-UCL.
DR GO; GO:0007190; P:activation of adenylate cyclase activity; IDA:HGNC-UCL.
DR GO; GO:0007171; P:activation of transmembrane receptor protein tyrosine kinase activity; TAS:ProtInc.
DR GO; GO:0071880; P:adenylate cyclase-activating adrenergic receptor signaling pathway; IBA:GO_Central.
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: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:0002032; P:desensitization of G protein-coupled receptor signaling pathway by arrestin; IDA:HGNC-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:0040015; P:negative regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0045986; P:negative regulation of smooth muscle contraction; IBA:GO_Central.
DR GO; GO:0002025; P:norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure; IBA:GO_Central.
DR GO; GO:2000969; P:positive regulation of AMPA receptor activity; IGI:ARUK-UCL.
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:2000481; P:positive regulation of cAMP-dependent protein kinase activity; TAS:ARUK-UCL.
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:0010739; P:positive regulation of protein kinase A signaling; IGI:ARUK-UCL.
DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IGI:ARUK-UCL.
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 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 SMART; SM01381; 7TM_GPCR_Srsx; 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; Endosome;
KW G-protein coupled receptor; Glycoprotein; Golgi apparatus; Hydroxylation;
KW Lipoprotein; Membrane; Palmitate; Phosphoprotein; 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..34
FT /note="Extracellular"
FT TRANSMEM 35..58
FT /note="Helical; Name=1"
FT TOPO_DOM 59..71
FT /note="Cytoplasmic"
FT TRANSMEM 72..95
FT /note="Helical; Name=2"
FT TOPO_DOM 96..106
FT /note="Extracellular"
FT TRANSMEM 107..129
FT /note="Helical; Name=3"
FT TOPO_DOM 130..150
FT /note="Cytoplasmic"
FT TRANSMEM 151..174
FT /note="Helical; Name=4"
FT TOPO_DOM 175..196
FT /note="Extracellular"
FT TRANSMEM 197..220
FT /note="Helical; Name=5"
FT TOPO_DOM 221..274
FT /note="Cytoplasmic"
FT TRANSMEM 275..298
FT /note="Helical; Name=6"
FT TOPO_DOM 299..305
FT /note="Extracellular"
FT TRANSMEM 306..329
FT /note="Helical; Name=7"
FT TOPO_DOM 330..413
FT /note="Cytoplasmic"
FT REGION 392..413
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 410..413
FT /note="PDZ-binding"
FT COMPBIAS 394..413
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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="(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="(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="(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:0000305"
FT MOD_RES 356
FT /note="Phosphoserine; by BARK"
FT /evidence="ECO:0000305"
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 DISULFID 184..190
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 265
FT /note="C->A: Loss of ligand-induced palmitoylation."
FT /evidence="ECO:0000269|PubMed:27481942"
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 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:3SN6"
FT HELIX 197..207
FT /evidence="ECO:0007829|PDB:2RH1"
FT HELIX 209..229
FT /evidence="ECO:0007829|PDB:2RH1"
FT TURN 235..239
FT /evidence="ECO:0007829|PDB:2R4R"
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..339
FT /evidence="ECO:0007829|PDB:2RH1"
FT TURN 340..342
FT /evidence="ECO:0007829|PDB:5JQH"
FT TURN 345..347
FT /evidence="ECO:0007829|PDB:2R4R"
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
