Reviewed, UniProtKB/Swiss-Prot P07550 (ADRB2_HUMAN)

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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	413 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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.
Subcellular location	Cell membrane; Multi-pass membrane protein.
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. Phosphorylated by PKA and BARK upon agonist stimulation, which mediates homologous desensitization of the receptor. PKA-mediated phosphorylation seems to facilitate phosphorylation by BARK. Phosphorylated upon DNA damage, probably by ATM or ATR.
Involvement in disease	Polymorphic forms of ADRB2 could impart some form of nocturnal asthma.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Glycoprotein Lipoprotein Palmitate Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	activation of MAPK activity Traceable author statement. Source: ProtInc activation of adenylate cyclase activity Inferred from direct assay. Source: HGNC activation of transmembrane receptor protein tyrosine kinase activity Traceable author statement. Source: ProtInc desensitization of G-protein coupled receptor protein signaling pathway by arrestin Inferred from direct assay. Source: HGNC endosome to lysosome transport Traceable author statement. Source: ProtInc positive regulation of MAPKKK cascade Inferred from direct assay. Source: HGNC receptor-mediated endocytosis Inferred from direct assay. Source: HGNC
Cellular component	endosome Traceable author statement. Source: ProtInc integral to plasma membrane Traceable author statement. Source: ProtInc lysosome Traceable author statement. Source: ProtInc receptor complex Inferred from direct assay. Source: HGNC
Molecular function	beta2-adrenergic receptor activity Inferred from direct assay. Source: HGNC norepinephrine binding Inferred from direct assay. Source: HGNC potassium channel regulator activity Inferred from direct assay. Source: UniProtKB protein homodimerization activity Inferred from direct assay. Source: HGNC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EIF2B1	Q14232	1	EBI-491169,EBI-491065

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 Potential

Transmembrane

35 – 58

24

1 Potential

Topological domain

59 – 71

13

Cytoplasmic Potential

Transmembrane

72 – 95

24

2 Potential

Topological domain

96 – 106

11

Extracellular Potential

Transmembrane

107 – 129

23

3 Potential

Topological domain

130 – 150

21

Cytoplasmic Potential

Transmembrane

151 – 174

24

4 Potential

Topological domain

175 – 196

22

Extracellular Potential

Transmembrane

197 – 220

24

5 Potential

Topological domain

221 – 274

54

Cytoplasmic Potential

Transmembrane

275 – 298

24

6 Potential

Topological domain

299 – 305

7

Extracellular Potential

Transmembrane

306 – 329

24

7 Potential

Topological domain

330 – 413

84

Cytoplasmic Potential

Sites

Site

113

1

Implicated in catechol agonist and antagonist binding By similarity

Site

204

1

Implicated in catechol agonist binding By similarity

Site

207

1

Implicated in catechol agonist binding By similarity

Amino acid modifications

Modified residue

246

1

Phosphoserine

Modified residue

261

1

Phosphoserine; by PKA Potential

Modified residue

262

1

Phosphoserine; by PKA Potential

Modified residue

345

1

Phosphoserine; by PKA

Modified residue

346

1

Phosphoserine; by PKA

Modified residue

355

1

Phosphoserine; by BARK Probable

Modified residue

356

1

Phosphoserine; by BARK Probable

Lipidation

341

1

S-palmitoyl cysteine

Glycosylation

6

1

N-linked (GlcNAc...) Probable

Glycosylation

15

1

N-linked (GlcNAc...) Probable

Disulfide bond

106 ↔ 184

By similarity

Natural variations

Natural variant

16

1

R → G Common polymorphism; in nocturnal asthma. dbSNP rs1042713.

VAR_003452

Natural variant

27

1

Q → E: dbSNP rs1042714.

VAR_003453

Natural variant

34

1

V → M

VAR_003454

Natural variant

159

1

I → F

VAR_009125

Natural variant

159

1

I → L

VAR_009124

Natural variant

164

1

T → I: dbSNP rs1800888.

VAR_003455

Natural variant

220

1

S → C: dbSNP rs3729943.

VAR_025101

Natural variant

375

1

K → R

VAR_009394

Experimental info

Mutagenesis

79

1

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

Mutagenesis

341

1

C → G: Uncoupled receptor

Mutagenesis

345 – 346

2

SS → AA: Delayed agonist-promoted desensitization

Sequence conflict

216

1

V → A in AAN01267. Ref.7

Secondary structure

1

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413

Helix Strand Turn

Details...

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

Helix

197 – 207

11

Helix

209 – 229

21

Helix

231 – 237

7

Helix

240 – 243

4

Helix

245 – 260

16

Helix

267 – 298

32

Helix

305 – 317

13

Helix

318 – 320

3

Helix

322 – 325

4

Helix

326 – 328

3

Helix

330 – 339

10

Sequences

	Sequence		Length	Mass (Da)
	P07550-1 [UniParc]. Last modified April 1, 1988. Version 1. Checksum: BAE4020E13764F81	FASTA	413	46,557
	10 20 30 40 50 60 MGQPGNGSAF LLAPNRSHAP DHDVTQQRDE 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]	"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: 3033609] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"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: 3025863] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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: 3026848] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[4]	"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: 2823249] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"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: 3034889] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"Beta-2-adrenergic receptor allele frequencies in two native American populations." Rupert J.R., Hochachka P.W. Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-16; LEU-159; PHE-159 AND ARG-375. Tissue: Blood.
[7]	"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]. Tissue: Heart.
[8]	SeattleSNPs program for genomic applications Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-16; GLU-27 AND CYS-220.
[9]	"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: 2831218] [Abstract] Cited for: MUTAGENESIS OF ASP-79.
[10]	"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: 2540197] [Abstract] Cited for: PALMITOYLATION AT CYS-341, MUTAGENESIS OF CYS-341.
[11]	"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: 11146000] [Abstract] Cited for: EFFECT OF PALMITOYLATION, PHOSPHORYLATION AT SER-345 AND SER-346, MUTAGENESIS OF 345-SER-SER-346.
[12]	"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: 10499588] [Abstract] Cited for: INTERACTION WITH SLC9A3R1.
[13]	"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: 12142540] [Abstract] Cited for: INTERACTION WITH GPRASP1.
[14]	"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: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-246, MASS SPECTROMETRY.
[15]	"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: 8383511] [Abstract] Cited for: VARIANTS GLY-16; GLU-27; MET-34 AND ILE-164.
[16]	"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: 7915137] [Abstract] Cited for: VARIANTS GLY-16 AND GLU-27, CHARACTERIZATION.
[17]	"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: 7706471] [Abstract] Cited for: VARIANT GLY-16.
+	Additional computationally mapped references.

Web resources

GeneReviews

SeattleSNPs

Cross-references