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P04274 (ADRB2_MESAU) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Beta-2 adrenergic receptor
Alternative name(s):
Beta-2 adrenoreceptor
Short name=Beta-2 adrenoceptor
Gene names
Name:ADRB2
OrganismMesocricetus auratus (Golden hamster)
Taxonomic identifier10036 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaCricetidaeCricetinaeMesocricetus

Protein attributes

Sequence length418 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain); the interaction is required when endocytosed to prevent degradation in lysosomes and promote recycling to the plasma membrane 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 componentCell membrane
Membrane
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Hydroxylation
Lipoprotein
Palmitate
Phosphoprotein
Ubl conjugation
Gene Ontology (GO)
   Biological_processactivation of adenylate cyclase activity

Inferred from sequence or structural similarity. Source: HGNC

adenylate cyclase-activating G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: InterPro

adrenergic receptor signaling pathway

Inferred from sequence or structural similarity. Source: GOC

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

regulation of smooth muscle contraction

Inferred from electronic annotation. Source: InterPro

regulation of vasodilation

Inferred from electronic annotation. Source: InterPro

   Cellular_componentintegral component of 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_functionbeta2-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 418418Beta-2 adrenergic receptor
PRO_0000069133

Regions

Topological domain1 – 3434Extracellular By similarity
Transmembrane35 – 5824Helical; Name=1; By similarity
Topological domain59 – 7113Cytoplasmic By similarity
Transmembrane72 – 9524Helical; Name=2; By similarity
Topological domain96 – 10611Extracellular By similarity
Transmembrane107 – 12923Helical; Name=3; By similarity
Topological domain130 – 15021Cytoplasmic By similarity
Transmembrane151 – 17424Helical; Name=4; By similarity
Topological domain175 – 19622Extracellular By similarity
Transmembrane197 – 22024Helical; Name=5; By similarity
Topological domain221 – 27454Cytoplasmic By similarity
Transmembrane275 – 29824Helical; Name=6; By similarity
Topological domain299 – 3057Extracellular By similarity
Transmembrane306 – 32924Helical; Name=7; By similarity
Topological domain330 – 41889Cytoplasmic By similarity
Region193 – 20715Agonist and antagonist binding By similarity
Region286 – 2938Agonist and antagonist binding By similarity
Region312 – 3165Agonist and antagonist binding By similarity
Motif415 – 4184PDZ-binding

Sites

Binding site1131Agonist or antagonist By similarity
Binding site1181Agonist or antagonist By similarity

Amino acid modifications

Modified residue1411Phosphotyrosine By similarity
Modified residue2611Phosphoserine; by PKA Potential
Modified residue2621Phosphoserine; by PKA Potential
Modified residue3451Phosphoserine; by PKA By similarity
Modified residue3461Phosphoserine; by PKA By similarity
Modified residue3551Phosphoserine; by BARK Probable
Modified residue3561Phosphoserine; by BARK Probable
Modified residue38714-hydroxyproline By similarity
Modified residue40014-hydroxyproline By similarity
Lipidation3411S-palmitoyl cysteine By similarity
Glycosylation61N-linked (GlcNAc...)
Glycosylation151N-linked (GlcNAc...)
Disulfide bond106 ↔ 191 By similarity
Disulfide bond184 ↔ 190 By similarity

Experimental info

Mutagenesis791D → A: Small decrease in agonist binding. No effect on antagonist binding. Ref.4
Mutagenesis1131D → A: Drastic decrease in agonist and antagonist binding. Stimulates adenylyl cyclase activity. Ref.4
Mutagenesis2041S → A: Decrease in catechol agonist binding. Ref.3
Mutagenesis2071S → A: Decrease in catechol agonist binding. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P04274 [UniParc].

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

FASTA41846,861
        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 

« Hide

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.
RefSeqNP_001268877.1. NM_001281948.1.

3D structure databases

ProteinModelPortalP04274.
SMRP04274. Positions 29-348.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-194411.

Chemistry

ChEMBLCHEMBL5943.

Protein family/group databases

GPCRDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID101836719.

Organism-specific databases

CTD154.

Phylogenomic databases

HOVERGENHBG106962.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR002233. ADR_fam.
IPR000332. ADRB2_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERPTHR24248:SF21. PTHR24248:SF21. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR01103. ADRENERGICR.
PR00562. ADRENRGCB2AR.
PR00237. GPCRRHODOPSN.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameADRB2_MESAU
AccessionPrimary (citable) accession number: P04274
Entry history
Integrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: March 20, 1987
Last modified: June 11, 2014
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries