Beta-2 adrenergic receptor - Mesocricetus auratus (Golden hamster)

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P04274 (ADRB2_MESAU) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 97. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

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

Organism

Mesocricetus auratus (Golden hamster)

Taxonomic identifier

10036 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Cricetidae › Cricetinae › Mesocricetus

Protein attributes

Sequence length	418 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 By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein By similarity. Note: Colocalizes with VHL on cell membranes By similarity.
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 By similarity. Phosphorylated by PKA and BARK upon agonist stimulation, which mediates homologous desensitization of the receptor. PKA-mediated phosphorylation seems to facilitate phosphorylation by BARK By similarity. Phosphorylation of Tyr-141 is induced by insulin and leads to supersensitization of the receptor By similarity. 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 By similarity. Hydroxylation by EGLN3 occurs only under normoxia and increases the interaction with VHL and the subsequent ubiquitination and degradation of ADRB2 By similarity.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB2 sub-subfamily.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Hydroxylation Lipoprotein Palmitate Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological_process	activation of adenylate cyclase activity Inferred from sequence or structural similarity. Source: HGNC desensitization of G-protein coupled receptor protein signaling pathway by arrestin Inferred from sequence or structural similarity. Source: HGNC positive regulation of MAPK cascade Inferred from sequence or structural similarity. Source: HGNC receptor-mediated endocytosis Inferred from sequence or structural similarity. Source: HGNC
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell receptor complex Inferred from sequence or structural similarity. Source: HGNC
Molecular_function	beta2-adrenergic receptor activity Inferred from sequence or structural similarity. Source: HGNC norepinephrine binding Inferred from sequence or structural similarity. Source: HGNC protein homodimerization activity Inferred from sequence or structural similarity. Source: HGNC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 418

418

Beta-2 adrenergic receptor

PRO_0000069133

Regions

Topological domain

1 – 34

Extracellular By similarity

Transmembrane

35 – 58

Helical; Name=1; By similarity

Topological domain

59 – 71

Cytoplasmic By similarity

Transmembrane

72 – 95

Helical; Name=2; By similarity

Topological domain

96 – 106

Extracellular By similarity

Transmembrane

107 – 129

Helical; Name=3; By similarity

Topological domain

130 – 150

Cytoplasmic By similarity

Transmembrane

151 – 174

Helical; Name=4; By similarity

Topological domain

175 – 196

Extracellular By similarity

Transmembrane

197 – 220

Helical; Name=5; By similarity

Topological domain

221 – 274

Cytoplasmic By similarity

Transmembrane

275 – 298

Helical; Name=6; By similarity

Topological domain

299 – 305

Extracellular By similarity

Transmembrane

306 – 329

Helical; Name=7; By similarity

Topological domain

330 – 418

Cytoplasmic By similarity

Region

193 – 207

Agonist and antagonist binding By similarity

Region

286 – 293

Agonist and antagonist binding By similarity

Region

312 – 316

Agonist and antagonist binding By similarity

Sites

Binding site

113

Agonist or antagonist By similarity

Binding site

118

Agonist or antagonist By similarity

Amino acid modifications

Modified residue

141

Phosphotyrosine By similarity

Modified residue

261

Phosphoserine; by PKA Potential

Modified residue

262

Phosphoserine; by PKA Potential

Modified residue

345

Phosphoserine; by PKA By similarity

Modified residue

346

Phosphoserine; by PKA By similarity

Modified residue

355

Phosphoserine; by BARK Probable

Modified residue

356

Phosphoserine; by BARK Probable

Modified residue

387

4-hydroxyproline By similarity

Modified residue

400

4-hydroxyproline By similarity

Lipidation

341

S-palmitoyl cysteine By similarity

Glycosylation

N-linked (GlcNAc...)

Glycosylation

N-linked (GlcNAc...)

Disulfide bond

106 ↔ 191

By similarity

Disulfide bond

184 ↔ 190

By similarity

Experimental info

Mutagenesis

D → A: Small decrease in agonist binding. No effect on antagonist binding. Ref.4

Mutagenesis

113

D → A: Drastic decrease in agonist and antagonist binding. Stimulates adenylyl cyclase activity. Ref.4

Mutagenesis

204

S → A: Decrease in catechol agonist binding. Ref.3

Mutagenesis

207

S → A: Decrease in catechol agonist binding. Ref.3

Sequences

Sequence

Length

Mass (Da)

Tools

P04274 [UniParc].

Last modified March 20, 1987. Version 1.
Checksum: 9B20478F91FB284E
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FASTA

418

46,861

        10         20         30         40         50         60 
MGPPGNDSDF LLTTNGSHVP DHDVTEERDE AWVVGMAILM SVIVLAIVFG NVLVITAIAK 

        70         80         90        100        110        120 
FERLQTVTNY FITSLACADL VMGLAVVPFG ASHILMKMWN FGNFWCEFWT SIDVLCVTAS 

       130        140        150        160        170        180 
IETLCVIAVD RYIAITSPFK YQSLLTKNKA RMVILMVWIV SGLTSFLPIQ MHWYRATHQK 

       190        200        210        220        230        240 
AIDCYHKETC CDFFTNQAYA IASSIVSFYV PLVVMVFVYS RVFQVAKRQL QKIDKSEGRF 

       250        260        270        280        290        300 
HSPNLGQVEQ DGRSGHGLRR SSKFCLKEHK ALKTLGIIMG TFTLCWLPFF IVNIVHVIQD 

       310        320        330        340        350        360 
NLIPKEVYIL LNWLGYVNSA FNPLIYCRSP DFRIAFQELL CLRRSSSKAY GNGYSSNSNG 

       370        380        390        400        410 
KTDYMGEASG CQLGQEKESE RLCEDPPGTE SFVNCQGTVP SLSLDSQGRN CSTNDSPL

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References

[1]	"Cloning of the gene and cDNA for mammalian beta-adrenergic receptor and homology with rhodopsin." Dixon R.A.F., Kobilka B.K., Strader D.J., Benovic J.L., Dohlman H.G., Frielle T., Bolanowski M.A., Bennett C.D., Rands E., Diehl R.E., Mumford R.A., Slater E.E., Sigal I.S., Caron M.G., Lefkowitz R.J., Strader C.D. Nature 321:75-79(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lung.
[2]	"Mutational analysis of beta-adrenergic receptor glycosylation." Rands E., Candelore M.R., Cheung A.H., Will W.S., Strader C.D., Dixon R.A.F. J. Biol. Chem. 265:10759-10764(1990) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS TO CONFIRM GLYCOSYLATION SITES.
[3]	"Identification of two serine residues involved in agonist activation of the beta-adrenergic receptor." Strader C.D., Candelore M.R., Hill W.S., Sigal I.S., Dixon R.A.F. J. Biol. Chem. 264:13572-13578(1989) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF SER-204 AND SER-207.
[4]	"Conserved aspartic acid residues 79 and 113 of the beta-adrenergic receptor have different roles in receptor function." Strader C.D., Sigal I.S., Candelore M.R., Rands E., Hill W.S., Dixon R.A.F. J. Biol. Chem. 263:10267-10271(1988) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ASP-79 AND ASP-113.
[5]	"Three-dimensional structure for the beta 2 adrenergic receptor protein based on computer modeling studies." Huss K.M., Lybrand T.P. J. Mol. Biol. 225:859-871(1992) [PubMed] [Europe PMC] [Abstract] Cited for: 3D-STRUCTURE MODELING.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X03804 mRNA. Translation: CAA27430.1.
3D structure databases
ProteinModelPortal	P04274.
SMR	P04274. Positions 29-348.
ModBase	Search...
Protein family/group databases
GPCRDB	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Phylogenomic databases
HOVERGEN	HBG106962.
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
ChEMBL	CHEMBL5943.

Entry information

Entry name

ADRB2_MESAU

Accession

Primary (citable) accession number: P04274

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 20, 1987
Last sequence update:	March 20, 1987
Last modified:	April 3, 2013
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein family/group databases

Protocols and materials databases

Phylogenomic databases

Family and domain databases

Other

Entry information

Relevant documents