Beta-2 adrenergic receptor - Rattus norvegicus (Rat)

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P10608 (ADRB2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 117. History...

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

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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
Synonyms:	Adrb2r

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	418 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript 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. 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
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adenylate cyclase-activating G-protein coupled receptor signaling pathway Inferred from direct assay PubMed 2153813. Source: RGD diaphragm contraction Inferred from direct assay PubMed 17362795. Source: RGD negative regulation of angiogenesis Inferred from mutant phenotype PubMed 22495178. Source: RGD negative regulation of inflammatory response Inferred from direct assay PubMed 15285793. Source: RGD negative regulation of ossification Inferred from mutant phenotype PubMed 16177600. Source: RGD negative regulation of urine volume Inferred from mutant phenotype PubMed 7912752. Source: RGD positive regulation of apoptotic process Inferred from mutant phenotype PubMed 15591297. Source: RGD positive regulation of cell proliferation Inferred from direct assay PubMed 16005083. Source: RGD positive regulation of potassium ion transport Inferred from direct assay PubMed 6247002. Source: RGD positive regulation of skeletal muscle tissue growth Inferred from mutant phenotype PubMed 16177600. Source: RGD positive regulation of sodium ion transport Inferred from direct assay PubMed 6247002. Source: RGD positive regulation of the force of heart contraction by epinephrine Inferred from direct assay PubMed 19133992. Source: RGD positive regulation of vasodilation Inferred from direct assay PubMed 15351777. Source: RGD regulation of calcium ion transport Inferred from direct assay PubMed 12514203 PubMed 19133992. Source: RGD regulation of excitatory postsynaptic membrane potential Inferred from mutant phenotype PubMed 17175110. Source: RGD regulation of sensory perception of pain Inferred from mutant phenotype PubMed 11569616. Source: RGD response to hypoxia Inferred from expression pattern PubMed 21562317. Source: RGD synaptic transmission, glutamatergic Inferred from mutant phenotype PubMed 17175110. Source: RGD vasodilation by norepinephrine-epinephrine involved in regulation of systemic arterial blood pressure Inferred from direct assay PubMed 6381693. Source: RGD wound healing Inferred from mutant phenotype PubMed 19320892. Source: RGD
Cellular_component	axon Inferred from direct assay PubMed 15682824. Source: RGD caveola Inferred from direct assay PubMed 15961389. Source: RGD dendritic spine Inferred from direct assay PubMed 11441182. Source: RGD endosome Inferred from direct assay PubMed 12932836. Source: RGD integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW neuronal cell body membrane Inferred from direct assay PubMed 11441182. Source: RGD nucleus Inferred from direct assay PubMed 17337326. Source: RGD sarcolemma Inferred from direct assay PubMed 15961389. Source: RGD
Molecular_function	PDZ domain binding Traceable author statement PubMed 10995758. Source: RGD beta2-adrenergic receptor activity Inferred from direct assay PubMed 12514203 PubMed 6247002 PubMed 6381693. Source: RGD dopamine binding Inferred from direct assay PubMed 6381693. Source: RGD drug binding Inferred from direct assay PubMed 12875885 PubMed 6289140 PubMed 6381693. Source: RGD epinephrine binding Inferred from direct assay PubMed 6381693. Source: RGD norepinephrine binding Inferred from direct assay PubMed 6381693. Source: RGD
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_0000069136

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

246

Phosphoserine 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...) Probable

Glycosylation

N-linked (GlcNAc...) Probable

Disulfide bond

106 ↔ 191

By similarity

Disulfide bond

184 ↔ 190

By similarity

Experimental info

Sequence conflict

262

S → F in AAA89068. Ref.2

Sequence conflict

334

I → Y in AAA89068. Ref.2

Sequences

Sequence

Length

Mass (Da)

Tools

P10608 [UniParc].

Last modified July 1, 1989. Version 1.
Checksum: 907B2882AFC02AC5
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FASTA

418

46,891

        10         20         30         40         50         60 
MEPHGNDSDF LLAPNGSRAP GHDITQERDE AWVVGMAILM SVIVLAIVFG NVLVITAIAK 

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

       130        140        150        160        170        180 
IETLCVIAVD RYVAITSPFK YQSLLTKNKA RVVILMVWIV SGLTSFLPIQ MHWYRATHKQ 

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

       250        260        270        280        290        300 
HAQNLSQVEQ DGRSGHGLRS SSKFCLKEHK ALKTLGIIMG TFTLCWLPFF IVNIVHVIRA 

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

       370        380        390        400        410 
RTDYTGEQSA YQLGQEKENE LLCEEAPGME GFVNCQGTVP SLSIDSQGRN CNTNDSPL

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References

[1]	"Primary structure of rat cardiac beta-adrenergic and muscarinic cholinergic receptors obtained by automated DNA sequence analysis: further evidence for a multigene family." Gocayne J.D., Robinson D.A., Fitzgerald M.G., Chung F.-Z., Kerlavage A.R., Lentes K.-U., Lai J., Wang C.-D., Fraser C.M., Venter J.C. Proc. Natl. Acad. Sci. U.S.A. 84:8296-8300(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Primary structure of the rat beta-2 adrenergic receptor gene." Buckland P.R., Hill R.M., Tidmarsh S.F., McGuffin P. Nucleic Acids Res. 18:682-682(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Liver.
[3]	"Sequence of the 5' regulatory domain of the gene encoding the rat beta 2-adrenergic receptor." Jiang L., Kunos G. Gene 163:331-332(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Sprague-Dawley.
[4]	"Structural and functional analysis of the 5'-flanking region of the rat beta 2-adrenergic receptor gene." McGraw D.W., Jacobi S.E., Hiller F.C., Cornett L.E. Biochim. Biophys. Acta 1305:135-138(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-23.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	J03024 mRNA. Translation: AAA40675.1. X17607 Genomic DNA. Translation: CAA35609.1. L39264 Genomic DNA. Translation: AAA89068.1. U35448 Genomic DNA. Translation: AAC52449.1.
IPI	IPI00192309.
PIR	S10855.
UniGene	Rn.10206.
3D structure databases
ProteinModelPortal	P10608.
SMR	P10608. Positions 29-348.
ModBase	Search...
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P10608.
Proteomic databases
PRIDE	P10608.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
UCSC	RGD:2060. rat.
Organism-specific databases
RGD	2060. Adrb2.
Phylogenomic databases
eggNOG	NOG262978.
HOGENOM	HOG000239242.
HOVERGEN	HBG106962.
InParanoid	P10608.
OrthoDB	EOG4WQ12W.
Gene expression databases
ArrayExpress	P10608.
Genevestigator	P10608.
GermOnline	ENSRNOG00000019217. Rattus norvegicus.
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	P10608.
ChEMBL	CHEMBL3754.

Entry information

Entry name

ADRB2_RAT

Accession

Primary (citable) accession number: P10608
Secondary accession number(s): Q6LCR3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	April 3, 2013
This is version 117 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

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents