P07550 (ADRB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Beta-2 adrenergic receptor

Alternative name(s):
Beta-2 adrenoreceptor
Short name=Beta-2 adrenoceptor

Gene names

Name:	ADRB2
Synonyms:	ADRB2R, B2AR

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	413 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine.
Subunit structure	Binds SLC9A3R1 and GPRASP1. Interacts with ARRB1 and ARRB2. Interacts with SRC, USP20 and USP33. Interacts with VHL; the interaction, which is increased on hydroxylation of ADRB2, ubiquitinates ADRB2 leading to its degradation. Interacts with EGLN3; the interaction hydroxylates ADRB2 facilitating VHL-E3 ligase-mediated ubiquitination. Ref.18 Ref.19 Ref.20 Ref.21 Ref.23 Ref.25 Ref.26
Subcellular location	Cell membrane; Multi-pass membrane protein. Note: Colocalizes with VHL at the cell membrane. Ref.26
Post-translational modification	Palmitoylated; may reduce accessibility of Ser-345 and Ser-346 by anchoring Cys-341 to the plasma membrane. Agonist stimulation promotes depalmitoylation and further allows Ser-345 and Ser-346 phosphorylation. Ref.16 Ref.22 Ref.28 Ref.29 Phosphorylated by PKA and BARK upon agonist stimulation, which mediates homologous desensitization of the receptor. PKA-mediated phosphorylation seems to facilitate phosphorylation by BARK. Ref.17 Ref.22 Phosphorylation of Tyr-141 is induced by insulin and leads to supersensitization of the receptor. Polyubiquitinated. Agonist-induced ubiquitination leads to sort internalized receptors to the lysosomes for degradation. Deubiquitination by USP20 and USP33, leads to ADRB2 recycling and resensitization after prolonged agonist stimulation. USP20 and USP33 are constitutively associated and are dissociated immediately after agonist stimulation. Ubiquitination by the VHL-E3 ligase complex is oxygen-dependent. Hydroxylation by EGLN3 occurs only under normoxia and increases the interaction with VHL and the subsequent ubiquitination and degradation of ADRB2.
Polymorphism	The Gly-16 allele is overrepresented in individuals affected by nocturnal asthma as compared to controls, and appears to be an important genetic factor in the expression of this asthmatic phenotype.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB2 sub-subfamily.
Sequence caution	The sequence BAD96745.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Hydroxylation Lipoprotein Palmitate Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of adenylate cyclase activity Inferred from direct assay PubMed 15123695. Source: HGNC activation of transmembrane receptor protein tyrosine kinase activity Traceable author statement PubMed 10734107. Source: ProtInc adenylate cyclase-activating G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: Compara adenylate cyclase-modulating G-protein coupled receptor signaling pathway Traceable author statement Ref.5. Source: ProtInc bone resorption Inferred from electronic annotation. Source: Compara brown fat cell differentiation Inferred from electronic annotation. Source: Compara desensitization of G-protein coupled receptor protein signaling pathway by arrestin Inferred from direct assay PubMed 15123695. Source: HGNC diet induced thermogenesis Inferred from electronic annotation. Source: Compara endosome to lysosome transport Traceable author statement PubMed 9507004. Source: ProtInc heat generation Inferred from electronic annotation. Source: Compara negative regulation of multicellular organism growth Inferred from electronic annotation. Source: Compara negative regulation of smooth muscle contraction Inferred from electronic annotation. Source: Compara positive regulation of MAPK cascade Inferred from direct assay PubMed 15123695. Source: HGNC positive regulation of bone mineralization Inferred from electronic annotation. Source: Compara positive regulation of protein ubiquitination Inferred from mutant phenotype PubMed 19372219. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara receptor-mediated endocytosis Inferred from direct assay PubMed 15123695. Source: HGNC regulation of sodium ion transport Inferred from electronic annotation. Source: Compara response to cold Inferred from electronic annotation. Source: Compara vasodilation by norepinephrine-epinephrine involved in regulation of systemic arterial blood pressure Inferred from electronic annotation. Source: Compara
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: Compara endosome Traceable author statement PubMed 10734107. Source: ProtInc integral to plasma membrane Inferred from direct assay PubMed 12297500. Source: BHF-UCL lysosome Traceable author statement PubMed 9507004. Source: ProtInc nucleus Inferred from electronic annotation. Source: Compara receptor complex Inferred from direct assay PubMed 15123695. Source: HGNC
Molecular_function	beta2-adrenergic receptor activity Inferred from direct assay PubMed 15123695. Source: HGNC norepinephrine binding Inferred from direct assay PubMed 15123695. Source: HGNC potassium channel regulator activity Inferred from direct assay PubMed 12297500. Source: BHF-UCL protein homodimerization activity Inferred from direct assay PubMed 15123695. Source: HGNC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 413

413

Beta-2 adrenergic receptor

PRO_0000069130

Regions

Topological domain

1 – 34

34

Extracellular Ref.27 Ref.28 Ref.29

Transmembrane

35 – 58

24

Helical; Name=1

Topological domain

59 – 71

13

Cytoplasmic Ref.27 Ref.28 Ref.29

Transmembrane

72 – 95

24

Helical; Name=2

Topological domain

96 – 106

11

Extracellular Ref.27 Ref.28 Ref.29

Transmembrane

107 – 129

23

Helical; Name=3

Topological domain

130 – 150

21

Cytoplasmic Ref.27 Ref.28 Ref.29

Transmembrane

151 – 174

24

Helical; Name=4

Topological domain

175 – 196

22

Extracellular Ref.27 Ref.28 Ref.29

Transmembrane

197 – 220

24

Helical; Name=5

Topological domain

221 – 274

54

Cytoplasmic Ref.27 Ref.28 Ref.29

Transmembrane

275 – 298

24

Helical; Name=6

Topological domain

299 – 305

7

Extracellular Ref.27 Ref.28 Ref.29

Transmembrane

306 – 329

24

Helical; Name=7

Topological domain

330 – 413

84

Cytoplasmic Ref.27 Ref.28 Ref.29

Region

193 – 207

15

Agonist and antagonist binding

Region

286 – 293

8

Agonist and antagonist binding

Region

312 – 316

5

Agonist and antagonist binding

Sites

Binding site

113

1

Agonist or antagonist

Binding site

118

1

Agonist or antagonist

Amino acid modifications

Modified residue

141

1

Phosphotyrosine Ref.17

Modified residue

246

1

Phosphoserine Ref.24

Modified residue

261

1

Phosphoserine; by PKA Potential

Modified residue

262

1

Phosphoserine; by PKA Potential

Modified residue

345

1

Phosphoserine; by PKA Ref.22

Modified residue

346

1

Phosphoserine; by PKA Ref.22

Modified residue

355

1

Phosphoserine; by BARK Probable

Modified residue

356

1

Phosphoserine; by BARK Probable

Modified residue

382

1

4-hydroxyproline Ref.26

Modified residue

395

1

4-hydroxyproline Ref.26

Lipidation

341

1

S-palmitoyl cysteine Ref.16 Ref.22 Ref.28 Ref.29

Glycosylation

6

1

N-linked (GlcNAc...) Probable

Glycosylation

15

1

N-linked (GlcNAc...) Probable

Disulfide bond

106 ↔ 191

Ref.28 Ref.29

Disulfide bond

184 ↔ 190

Ref.28 Ref.29

Natural variations

Natural variant

15

1

N → S.
Corresponds to variant rs33973603 [ dbSNP | Ensembl ].

VAR_049373

Natural variant

16

1

G → R Common polymorphism. Ref.2 Ref.3 Ref.4 Ref.6 Ref.8 Ref.14 Ref.30 Ref.31
Corresponds to variant rs1042713 [ dbSNP | Ensembl ].

VAR_003452

Natural variant

27

1

E → Q. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.10 Ref.11 Ref.12 Ref.14 Ref.30
Corresponds to variant rs1042714 [ dbSNP | Ensembl ].

VAR_003453

Natural variant

34

1

V → M. Ref.6

VAR_003454

Natural variant

159

1

I → F. Ref.7

VAR_009125

Natural variant

159

1

I → L. Ref.7

VAR_009124

Natural variant

164

1

T → I. Ref.6
Corresponds to variant rs1800888 [ dbSNP | Ensembl ].

VAR_003455

Natural variant

220

1

S → C. Ref.11
Corresponds to variant rs3729943 [ dbSNP | Ensembl ].

VAR_025101

Natural variant

375

1

K → R. Ref.7

VAR_009394

Experimental info

Mutagenesis

79

1

D → N: Affects binding of catecholamines, and produces an uncoupling between the receptor and stimulatory G proteins. Ref.15 Ref.22

Mutagenesis

141

1

Y → F: Abolishes insulin-induced tyrosine phosphorylation and insulin-induced receptor supersensitization. Ref.17 Ref.22

Mutagenesis

341

1

C → G: Uncoupled receptor. Ref.16 Ref.22

Mutagenesis

345 – 346

2

SS → AA: Delayed agonist-promoted desensitization. Ref.22

Mutagenesis

350

1

Y → A: Does not affect insulin-induced tyrosine phosphorylation or insulin-induced receptor supersensitization. Ref.17 Ref.22

Mutagenesis

354

1

Y → A: Does not affect insulin-induced tyrosine phosphorylation or insulin-induced receptor supersensitization. Ref.17 Ref.22

Mutagenesis

366

1

Y → F: Does not affect insulin-induced tyrosine phosphorylation or insulin-induced receptor supersensitization. Ref.17 Ref.22

Sequence conflict

71

1

F → L in BAG35969. Ref.9

Sequence conflict

216

1

V → A in AAN01267. Ref.8

Sequence conflict

261

1

S → P in BAD96745. Ref.10

Sequence conflict

402

1

Q → P in AAH12481. Ref.14

Secondary structure

1

.

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413

Helix Strand Turn

Details...

Beta strand

25 – 27

3

Helix

31 – 60

30

Helix

62 – 64

3

Helix

67 – 85

19

Helix

87 – 96

10

Helix

102 – 136

35

Beta strand

137 – 139

3

Helix

147 – 170

24

Turn

171 – 174

4

Helix

179 – 186

8

Beta strand

187 – 189

3

Helix

197 – 207

11

Helix

209 – 229

21

Turn

235 – 239

5

Helix

267 – 298

32

Beta strand

299 – 301

3

Helix

305 – 317

13

Helix

318 – 320

3

Helix

322 – 325

4

Helix

326 – 328

3

Helix

330 – 339

10

Turn

345 – 347

3

Sequences

	Sequence		Length	Mass (Da)
	P07550 [UniParc]. Last modified May 18, 2010. Version 3. Checksum: 408C22731C6EDFBE	FASTA	413	46,459
	10 20 30 40 50 60 MGQPGNGSAF LLAPNGSHAP DHDVTQERDE VWVVGMGIVM SLIVLAIVFG NVLVITAIAK 70 80 90 100 110 120 FERLQTVTNY FITSLACADL VMGLAVVPFG AAHILMKMWT FGNFWCEFWT SIDVLCVTAS 130 140 150 160 170 180 IETLCVIAVD RYFAITSPFK YQSLLTKNKA RVIILMVWIV SGLTSFLPIQ MHWYRATHQE 190 200 210 220 230 240 AINCYANETC CDFFTNQAYA IASSIVSFYV PLVIMVFVYS RVFQEAKRQL QKIDKSEGRF 250 260 270 280 290 300 HVQNLSQVEQ DGRTGHGLRR SSKFCLKEHK ALKTLGIIMG TFTLCWLPFF IVNIVHVIQD 310 320 330 340 350 360 NLIRKEVYIL LNWIGYVNSG FNPLIYCRSP DFRIAFQELL CLRRSSLKAY GNGYSSNGNT 370 380 390 400 410 GEQSGYHVEQ EKENKLLCED LPGTEDFVGH QGTVPSDNID SQGRNCSTND SLL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequence analysis of the human brain beta-adrenergic receptor. Evolutionary relationship to rodent and avian beta-receptors and porcine muscarinic receptors." Chung F.-Z., Lentes K.-U., Gocayne J.D., Fitzgerald M.G., Robinson D.A., Kerlavage A.R., Fraser C.M., Venter J.C. FEBS Lett. 211:200-206(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-27. Tissue: Brain.
[2]	"Delineation of the intronless nature of the genes for the human and hamster beta 2-adrenergic receptor and their putative promoter regions." Kobilka B.K., Frielle T., Dohlman H.G., Bolanowski M.A., Dixon R.A.F., Keller P., Caron M.G., Lefkowitz R.J. J. Biol. Chem. 262:7321-7327(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-16 AND GLN-27.
[3]	"Primary structure of the human beta-adrenergic receptor gene." Schofield P.R., Rhee L.M., Peralta E.G. Nucleic Acids Res. 15:3636-3636(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-16 AND GLN-27.
[4]	"cDNA for the human beta 2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor." Kobilka B.K., Dixon R.A.F., Frielle T., Dohlman H.G., Bolanowski M.A., Sigal I.S., Yang-Feng T.L., Francke U., Caron M.G., Lefkowitz R.J. Proc. Natl. Acad. Sci. U.S.A. 84:46-50(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ARG-16 AND GLN-27.
[5]	"Structure of the gene for human beta 2-adrenergic receptor: expression and promoter characterization." Emorine L.J., Marullo S., Delavier-Klutchko C., Kaveri S.V., Durieu-Trautmann O., Strosberg A.D. Proc. Natl. Acad. Sci. U.S.A. 84:6995-6999(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLN-27.
[6]	"Mutations in the gene encoding for the beta 2-adrenergic receptor in normal and asthmatic subjects." Reihsaus E., Innis M., Macintyre N., Liggett S.B. Am. J. Respir. Cell Mol. Biol. 8:334-339(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-16; GLN-27; MET-34 AND ILE-164.
[7]	"Beta2-adrenergic receptor allele frequencies in the Quechua, a high altitude native population." Rupert J.L., Monsalve M.V., Devine D.V., Hochachka P.W. Ann. Hum. Genet. 64:135-143(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLN-27; LEU-159; PHE-159 AND ARG-375. Tissue: Blood.
[8]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Puhl H.L. III, Ikeda S.R., Aronstam R.S. Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ARG-16 AND GLN-27. Tissue: Heart.
[9]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[10]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-27. Tissue: Thyroid.
[11]	SeattleSNPs variation discovery resource Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLN-27 AND CYS-220.
[12]	NHLBI resequencing and genotyping service (RS&G) Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLN-27.
[13]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[14]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ARG-16 AND GLN-27. Tissue: Fetal brain, Leukocyte and Prostate.
[15]	"Site-directed mutagenesis and continuous expression of human beta-adrenergic receptors. Identification of a conserved aspartate residue involved in agonist binding and receptor activation." Chung F.-Z., Wang C.-D., Potter P.C., Venter J.C., Fraser C.M. J. Biol. Chem. 263:4052-4055(1988) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ASP-79.
[16]	"Palmitoylation of the human beta 2-adrenergic receptor. Mutation of Cys341 in the carboxyl tail leads to an uncoupled nonpalmitoylated form of the receptor." O'Dowd B.F., Hnatowich M., Caron M.G., Lefkowitz R.J., Bouvier M. J. Biol. Chem. 264:7564-7569(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PALMITOYLATION AT CYS-341, MUTAGENESIS OF CYS-341.
[17]	"Mutation of tyrosine-141 inhibits insulin-promoted tyrosine phosphorylation and increased responsiveness of the human beta 2-adrenergic receptor." Valiquette M., Parent S., Loisel T.P., Bouvier M. EMBO J. 14:5542-5549(1995) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF TYR-141; TYR-350; TYR-354 AND TYR-366, PHOSPHORYLATION AT TYR-141.
[18]	"Arrestin interactions with G protein-coupled receptors. Direct binding studies of wild type and mutant arrestins with rhodopsin, beta 2-adrenergic, and m2 muscarinic cholinergic receptors." Gurevich V.V., Dion S.B., Onorato J.J., Ptasienski J., Kim C.M., Sterne-Marr R., Hosey M.M., Benovic J.L. J. Biol. Chem. 270:720-731(1995) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ARRB1 AND ARRB2.
[19]	"Clathrin-mediated endocytosis of the beta-adrenergic receptor is regulated by phosphorylation/dephosphorylation of beta-arrestin1." Lin F.-T., Krueger K.M., Kendall H.E., Daaka Y., Fredericks Z.L., Pitcher J.A., Lefkowitz R.J. J. Biol. Chem. 272:31051-31057(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ARRB1.
[20]	"A kinase-regulated PDZ-domain interaction controls endocytic sorting of the beta2-adrenergic receptor." Cao T.T., Deacon H.W., Reczek D., Bretscher A., von Zastrow M. Nature 401:286-290(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SLC9A3R1.
[21]	"Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes." Luttrell L.M., Ferguson S.S.G., Daaka Y., Miller W.E., Maudsley S., Della Rocca G.J., Lin F.-T., Kawakatsu H., Owada K., Luttrell D.K., Caron M.G., Lefkowitz R.J. Science 283:655-661(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SRC AND ARRB1.
[22]	"The palmitoylation state of the beta(2)-adrenergic receptor regulates the synergistic action of cyclic AMP-dependent protein kinase and beta-adrenergic receptor kinase involved in its phosphorylation and desensitization." Moffett S., Rousseau G., Lagace M., Bouvier M. J. Neurochem. 76:269-279(2001) [PubMed] [Europe PMC] [Abstract] Cited for: EFFECT OF PALMITOYLATION, PHOSPHORYLATION AT SER-345 AND SER-346, MUTAGENESIS OF 345-SER-SER-346.
[23]	"Modulation of postendocytic sorting of G protein-coupled receptors." Whistler J.L., Enquist J., Marley A., Fong J., Gladher F., Tsuruda P., Murray S.R., Von Zastrow M. Science 297:615-620(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GPRASP1.
[24]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-246, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[25]	"The deubiquitinases USP33 and USP20 coordinate beta2 adrenergic receptor recycling and resensitization." Berthouze M., Venkataramanan V., Li Y., Shenoy S.K. EMBO J. 28:1684-1696(2009) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP20 AND USP33, INTERACTION WITH USP20 AND USP33.
[26]	"Oxygen-regulated beta(2)-adrenergic receptor hydroxylation by EGLN3 and ubiquitylation by pVHL." Xie L., Xiao K., Whalen E.J., Forrester M.T., Freeman R.S., Fong G., Gygi S.P., Lefkowitz R.J., Stamler J.S. Sci. Signal. 2:RA33-RA33(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EGLN3 AND VHL, SUBCELLULAR LOCATION, INDUCTION, UBIQUITINATION, HYDROXYLATION AT PRO-382 AND PRO-395, MASS SPECTROMETRY.
[27]	"Crystal structure of the human beta2 adrenergic G-protein-coupled receptor." Rasmussen S.G.F., Choi H.-J., Rosenbaum D.M., Kobilka T.S., Thian F.S., Edwards P.C., Burghammer M., Ratnala V.R.P., Sanishvili R., Fischetti R.F., Schertler G.F.X., Weis W.I., Kobilka B.K. Nature 450:383-387(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 1-365 IN COMPLEX WITH CARAZOLOL, TOPOLOGY.
[28]	"High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor." Cherezov V., Rosenbaum D.M., Hanson M.A., Rasmussen S.G.F., Thian F.S., Kobilka T.S., Choi H.-J., Kuhn P., Weis W.I., Kobilka B.K., Stevens R.C. Science 318:1258-1265(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-365 IN COMPLEX WITH CARAZOLOL AND CHOLESTEROL, DISULFIDE BONDS, TOPOLOGY, PALMITOYLATION AT CYS-341.
[29]	"A specific cholesterol binding site is established by the 2.8 A structure of the human beta2-adrenergic receptor." Hanson M.A., Cherezov V., Griffith M.T., Roth C.B., Jaakola V.P., Chien E.Y., Velasquez J., Kuhn P., Stevens R.C. Structure 16:897-905(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-365 IN COMPLEX WITH TIMOLOL AND CHOLESTEROL, DISULFIDE BONDS, TOPOLOGY, PALMITOYLATION AT CYS-341.
[30]	"Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties." Green S.A., Turki J., Innis M., Ligget S.B. Biochemistry 33:9414-9419(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ARG-16 AND GLN-27, CHARACTERIZATION.
[31]	"Genetic polymorphisms of the beta 2-adrenergic receptor in nocturnal and nonnocturnal asthma. Evidence that Gly16 correlates with the nocturnal phenotype." Turki J., Pak J., Green S.A., Martin R.J., Liggett S.B. J. Clin. Invest. 95:1635-1641(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ARG-16, ASSOCIATION OF GLY-16 WITH NOCTURNAL ASTHMA.
+	Additional computationally mapped references.

Web resources

GeneReviews

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X04827 mRNA. Translation: CAA28511.1.
Y00106 Genomic DNA. Translation: CAA68289.1.
M15169 mRNA. Translation: AAA88015.1.
J02960 Genomic DNA. Translation: AAA88017.1.
AF022953 Genomic DNA. Translation: AAB82148.1.
AF022954 Genomic DNA. Translation: AAB82149.1.
AF022955 Genomic DNA. Translation: AAB82150.1.
AF022956 Genomic DNA. Translation: AAB82151.1.
AF169225 Genomic DNA. Translation: AAD48036.1.
AF202305 Genomic DNA. Translation: AAF17569.1.
AF203386 Genomic DNA. Translation: AAF20199.1.
AY136741 mRNA. Translation: AAN01267.1.
AK313151 mRNA. Translation: BAG35969.1.
AK223025 mRNA. Translation: BAD96745.1. Different initiation.
DQ094845 Genomic DNA. Translation: AAY88739.1.
EU332834 Genomic DNA. Translation: ABY87523.1.
CH471062 Genomic DNA. Translation: EAW61798.1.
BC012481 mRNA. Translation: AAH12481.3.
BC063486 mRNA. Translation: AAH63486.2.
BC073856 mRNA. Translation: AAH73856.1.

IPI

IPI00465066.

PIR

QRHUB2. A27525.

RefSeq

NP_000015.1. NM_000024.5.

UniGene

Hs.2551.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1GQ4	X-ray	1.90	A	409-413	[»]
2R4R	X-ray	3.40	A	1-365	[»]
2R4S	X-ray	3.40	A	24-365	[»]
2RH1	X-ray	2.40	A	1-365	[»]
3D4S	X-ray	2.80	A	1-348	[»]
3KJ6	X-ray	3.40	A	2-365	[»]
3NY8	X-ray	2.84	A	1-348	[»]
3NY9	X-ray	2.84	A	1-348	[»]
3NYA	X-ray	3.16	A	1-348	[»]
3P0G	X-ray	3.50	A	1-365	[»]
3PDS	X-ray	3.50	A	25-348	[»]
3SN6	X-ray	3.20	R	29-365	[»]
4GBR	X-ray	3.99	A	29-365	[»]

ProteinModelPortal

P07550.

SMR

P07550. Positions 29-341.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-33948N.

IntAct

P07550. 1 interaction.

MINT

MINT-148142.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P07550.

Polymorphism databases

DMDM

296439450.

Proteomic databases

PaxDb

P07550.

PRIDE

P07550.

Protocols and materials databases

DNASU

154.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000305988; ENSP00000305372; ENSG00000169252.

GeneID

154.

KEGG

hsa:154.

UCSC

uc003lpr.2. human.

Organism-specific databases

CTD

154.

GeneCards

GC05P148186.

HGNC

HGNC:286. ADRB2.

HPA

HPA003431.

MIM

109690. gene+phenotype.

neXtProt

NX_P07550.

PharmGKB

PA39.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG262978.

HOVERGEN

HBG106962.

InParanoid

P07550.

KO

K04142.

OMA

KETCCDF.

OrthoDB

EOG4WQ12W.

PhylomeDB

P07550.

Enzyme and pathway databases

Pathway_Interaction_DB

arf6cyclingpathway. Arf6 signaling events.
arf6_traffickingpathway. Arf6 trafficking events.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P07550.

Bgee

P07550.

Genevestigator

P07550.

GermOnline

ENSG00000169252. Homo sapiens.

Family and domain databases

InterPro

IPR000332. Adrgc_rcpt_B2.
IPR002233. Adrnrgc_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]

Pfam

PF00001. 7tm_1. 1 hit.
[Graphical view]

PRINTS

PR01103. ADRENERGICR.
PR00562. ADRENRGCB2AR.
PR00237. GPCRRHODOPSN.

PROSITE

PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P07550.

ChEMBL

CHEMBL210.

DrugBank

DB00866. Alprenolol.
DB01274. Arformoterol.
DB01408. Bambuterol.
DB00612. Bisoprolol.
DB00901. Bitolterol.
DB01158. Bretylium.
DB00521. Carteolol.
DB01136. Carvedilol.
DB01407. Clenbuterol.
DB01151. Desipramine.
DB00668. Epinephrine.
DB01288. Fenoterol.
DB00983. Formoterol.
DB01064. Isoproterenol.
DB00598. Labetalol.
DB01210. Levobunolol.
DB01214. Metipranolol.
DB01203. Nadolol.
DB00368. Norepinephrine.
DB00816. Orciprenaline.
DB01580. Oxprenolol.
DB01359. Penbutolol.
DB00960. Pindolol.
DB01291. Pirbuterol.
DB01366. Procaterol.
DB00571. Propranolol.
DB00852. Pseudoephedrine.
DB00867. Ritodrine.
DB01001. Salbutamol.
DB00938. Salmeterol.
DB00871. Terbutaline.
DB00373. Timolol.

EvolutionaryTrace

P07550.

GenomeRNAi

154.

NextBio

613.

SOURCE

Search...

Entry information

Entry name

ADRB2_HUMAN

Accession

Primary (citable) accession number: P07550
Secondary accession number(s): B0LPE4 , B2R7X2, O14823, O14824, O14825, O14826, Q4JG18, Q53GA6, Q6GMT4, Q6P4D8, Q8NEQ9, Q96EC3, Q9UCZ0, Q9UCZ1, Q9UCZ2, Q9UCZ3, Q9UH95, Q9UHA1, Q9UMZ5

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 161 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.