P10608 (ADRB2_RAT) 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

Organism

Rattus norvegicus (Rat)

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. Phosphorylated upon DNA damage, probably by ATM or ATR 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
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	activation of adenylate cyclase activity by G-protein signaling pathway Inferred from direct assay. Source: RGD diaphragm contraction Inferred from direct assay. Source: RGD negative regulation of calcium ion transport via voltage-gated calcium channel activity Inferred from direct assay. Source: RGD negative regulation of inflammatory response Inferred from direct assay. Source: RGD negative regulation of ossification Inferred from mutant phenotype. Source: RGD negative regulation of urine volume Inferred from mutant phenotype. Source: RGD positive regulation of apoptotic process Inferred from mutant phenotype. Source: RGD positive regulation of calcium ion transport via voltage-gated calcium channel activity Inferred from direct assay. Source: RGD positive regulation of cell proliferation Inferred from direct assay. Source: RGD positive regulation of potassium ion transport Inferred from direct assay. Source: RGD positive regulation of skeletal muscle tissue growth Inferred from mutant phenotype. Source: RGD positive regulation of sodium ion transport Inferred from direct assay. Source: RGD positive regulation of the force of heart contraction by epinephrine Inferred from direct assay. Source: RGD positive regulation of vasodilation Inferred from direct assay. Source: RGD regulation of excitatory postsynaptic membrane potential Inferred from mutant phenotype. Source: RGD regulation of sensory perception of pain Inferred from mutant phenotype. Source: RGD synaptic transmission, glutamatergic Inferred from mutant phenotype. Source: RGD vasodilation by norepinephrine-epinephrine involved in regulation of systemic arterial blood pressure Inferred from direct assay. Source: RGD wound healing Inferred from mutant phenotype. Source: RGD
Cellular component	axon Inferred from direct assay. Source: RGD caveola Inferred from direct assay. Source: RGD dendritic spine Inferred from direct assay. Source: RGD endosome Inferred from direct assay. Source: RGD microsome Inferred from direct assay. Source: RGD neuronal cell body membrane Inferred from direct assay. Source: RGD nucleus Inferred from direct assay. Source: RGD sarcolemma Inferred from direct assay. Source: RGD
Molecular function	G-protein alpha-subunit binding Inferred from physical interaction. Source: RGD PDZ domain binding Traceable author statement. Source: RGD beta2-adrenergic receptor activity Inferred from direct assay. Source: RGD dopamine binding Inferred from direct assay. Source: RGD drug binding Inferred from direct assay. Source: RGD epinephrine binding Inferred from direct assay. Source: RGD ionotropic glutamate receptor binding Inferred from physical interaction. Source: RGD norepinephrine binding Inferred from direct assay. 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	34	Extracellular By similarity
	Transmembrane	35 – 58	24	Helical; Name=1; By similarity
	Topological domain	59 – 71	13	Cytoplasmic By similarity
	Transmembrane	72 – 95	24	Helical; Name=2; By similarity
	Topological domain	96 – 106	11	Extracellular By similarity
	Transmembrane	107 – 129	23	Helical; Name=3; By similarity
	Topological domain	130 – 150	21	Cytoplasmic By similarity
	Transmembrane	151 – 174	24	Helical; Name=4; By similarity
	Topological domain	175 – 196	22	Extracellular By similarity
	Transmembrane	197 – 220	24	Helical; Name=5; By similarity
	Topological domain	221 – 274	54	Cytoplasmic By similarity
	Transmembrane	275 – 298	24	Helical; Name=6; By similarity
	Topological domain	299 – 305	7	Extracellular By similarity
	Transmembrane	306 – 329	24	Helical; Name=7; By similarity
	Topological domain	330 – 418	89	Cytoplasmic By similarity
	Region	193 – 207	15	Agonist and antagonist binding By similarity
	Region	286 – 293	8	Agonist and antagonist binding By similarity
	Region	312 – 316	5	Agonist and antagonist binding By similarity
Sites
	Binding site	113	1	Agonist or antagonist By similarity
	Binding site	118	1	Agonist or antagonist By similarity
Amino acid modifications
	Modified residue	141	1	Phosphotyrosine By similarity
	Modified residue	246	1	Phosphoserine By similarity
	Modified residue	261	1	Phosphoserine; by PKA Potential
	Modified residue	262	1	Phosphoserine; by PKA Potential
	Modified residue	345	1	Phosphoserine; by PKA By similarity
	Modified residue	346	1	Phosphoserine; by PKA By similarity
	Modified residue	355	1	Phosphoserine; by BARK Probable
	Modified residue	356	1	Phosphoserine; by BARK Probable
	Modified residue	387	1	4-hydroxyproline By similarity
	Modified residue	400	1	4-hydroxyproline By similarity
	Lipidation	341	1	S-palmitoyl cysteine By similarity
	Glycosylation	6	1	N-linked (GlcNAc...) Probable
	Glycosylation	15	1	N-linked (GlcNAc...) Probable
	Disulfide bond	106 ↔ 191		By similarity
	Disulfide bond	184 ↔ 190		By similarity
Experimental info
	Sequence conflict	262	1	S → F in AAA89068. Ref.2
	Sequence conflict	334	1	I → Y in AAA89068. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P10608 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: 907B2882AFC02AC5	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

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: 2825184] [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: 2155412] [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: 7590294] [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: 8597598] [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-protein interaction databases
STRING	P10608.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P10608.
Proteomic databases
PRIDE	P10608.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
UCSC	NM_012492. rat.
Organism-specific databases
RGD	2060. Adrb2.
Phylogenomic databases
eggNOG	maNOG17463.
HOVERGEN	HBG106962.
InParanoid	P10608.
OrthoDB	EOG4WQ12W.
Gene expression databases
ArrayExpress	P10608.
Genevestigator	P10608.
GermOnline	ENSRNOG00000019217. Rattus norvegicus.
Family and domain databases
InterPro	IPR000276. 7TM_GPCR_Rhodpsn. IPR000332. Adrgc_rcpt_B2. IPR002233. Adrnrgc_rcpt. IPR017452. GPCR_Rhodpsn_supfam. [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...

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:	January 25, 2012
This is version 106 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program