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P18762 (ADRB2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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
Synonyms:Adrb2r
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length418 AA.
Sequence statusComplete.
Protein existenceEvidence 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. 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.

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
   Technical termComplete proteome
Reference proteome
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 direct assay PubMed 11557593Ref.1. Source: MGI

adrenergic receptor signaling pathway

Inferred from direct assay PubMed 11557593Ref.1PubMed 6321299PubMed 7738011PubMed 8693001PubMed 9305915. Source: GOC

bone resorption

Inferred from mutant phenotype PubMed 15724149. Source: MGI

brown fat cell differentiation

Inferred from genetic interaction PubMed 12387862. Source: MGI

desensitization of G-protein coupled receptor protein signaling pathway by arrestin

Inferred from sequence or structural similarity. Source: HGNC

diet induced thermogenesis

Inferred from genetic interaction PubMed 12161655. Source: MGI

heat generation

Inferred from genetic interaction PubMed 12161655. Source: MGI

negative regulation of multicellular organism growth

Inferred from genetic interaction PubMed 12387862. Source: MGI

negative regulation of smooth muscle contraction

Inferred from genetic interaction PubMed 12925702. Source: MGI

positive regulation of MAPK cascade

Inferred from sequence or structural similarity. Source: HGNC

positive regulation of bone mineralization

Inferred from mutant phenotype PubMed 15724149. Source: MGI

positive regulation of protein ubiquitination

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction PubMed 15724149. Source: MGI

receptor-mediated endocytosis

Inferred from sequence or structural similarity. Source: HGNC

regulation of sodium ion transport

Inferred from mutant phenotype PubMed 15016730. Source: MGI

regulation of systemic arterial blood pressure by norepinephrine-epinephrine

Inferred from mutant phenotype PubMed 10358008. Source: MGI

regulation of vasodilation

Inferred from electronic annotation. Source: InterPro

response to cold

Inferred from genetic interaction PubMed 12161655PubMed 12387862. Source: MGI

vasodilation by norepinephrine-epinephrine involved in regulation of systemic arterial blood pressure

Inferred from mutant phenotype PubMed 10358009. Source: MGI

   Cellular_componentapical plasma membrane

Inferred from direct assay PubMed 14625387. Source: MGI

integral component of plasma membrane

Inferred from electronic annotation. Source: Ensembl

membrane

Inferred from direct assay Ref.1PubMed 6321299. Source: MGI

nucleus

Inferred from direct assay PubMed 15791602. Source: MGI

plasma membrane

Inferred from sequence orthology PubMed 9235896. Source: MGI

receptor complex

Inferred from sequence or structural similarity. Source: HGNC

   Molecular_functionadenylate cyclase binding

Inferred from direct assay PubMed 12297500. Source: BHF-UCL

beta2-adrenergic receptor activity

Inferred from direct assay PubMed 11557593Ref.1PubMed 6321299PubMed 7738011PubMed 8693001PubMed 9305915. Source: MGI

enzyme binding

Inferred from physical interaction PubMed 19801680. Source: BHF-UCL

norepinephrine binding

Inferred from sequence or structural similarity. Source: HGNC

potassium channel regulator activity

Inferred from electronic annotation. Source: Ensembl

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_0000069134

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 residue2461Phosphoserine 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...) Probable
Glycosylation151N-linked (GlcNAc...) Probable
Disulfide bond106 ↔ 191 By similarity
Disulfide bond184 ↔ 190 By similarity

Experimental info

Sequence conflict211D → H in CAA33664. Ref.2
Sequence conflict94 – 952IL → TS in CAA33664. Ref.2
Sequence conflict2541S → T in CAA33664. Ref.2
Sequence conflict347 – 3482SK → FE in CAA33664. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P18762 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 51D1EC73D7619D58

FASTA41846,998
        10         20         30         40         50         60 
MGPHGNDSDF LLAPNGSRAP DHDVTQERDE AWVVGMAILM SVIVLAIVFG NVLVITAIAK 

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

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

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

       250        260        270        280        290        300 
HAQNLSQVEQ DGRSGHGLRR SSKFCLKEHK ALKTLGIIMG TFTLCWLPFF IVNIVHVIRD 

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

       370        380        390        400        410 
RTDYTGEPNT CQLGQEREQE LLCEDPPGME GFVNCQGTVP SLSVDSQGRN CSTNDSPL 

« Hide

References

« Hide 'large scale' references
[1]"Isoproterenol response following transfection of the mouse beta 2-adrenergic receptor gene into Y1 cells."
Allen J.M., Baetge E.E., Abrass I.B., Palmiter R.D.
EMBO J. 7:133-138(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Genetic regulation of beta 2-adrenergic receptors in 3T3-L1 fibroblasts."
Nakada M.T., Haskell K.M., Ecker D.J., Stadel J.M., Crooke S.T.
Biochem. J. 260:53-59(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Mammary gland.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X15643 Genomic DNA. Translation: CAA33664.1.
AK080241 mRNA. Translation: BAC37856.1.
CH466528 Genomic DNA. Translation: EDL09746.1.
BC032883 mRNA. Translation: AAH32883.1.
PIRS00260.
RefSeqNP_031446.2. NM_007420.3.
UniGeneMm.5598.

3D structure databases

ProteinModelPortalP18762.
SMRP18762. Positions 29-342.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-59568N.
IntActP18762. 5 interactions.
MINTMINT-1793203.

Chemistry

BindingDBP18762.
ChEMBLCHEMBL2111395.
GuidetoPHARMACOLOGY29.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP18762.

Proteomic databases

PRIDEP18762.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000053640; ENSMUSP00000062256; ENSMUSG00000045730.
GeneID11555.
KEGGmmu:11555.
UCSCuc008fcy.1. mouse.

Organism-specific databases

CTD154.
MGIMGI:87938. Adrb2.

Phylogenomic databases

eggNOGNOG262978.
GeneTreeENSGT00720000108411.
HOGENOMHOG000239242.
HOVERGENHBG106962.
InParanoidQ8BH38.
KOK04142.
OMAKETCCDF.
OrthoDBEOG7BS4BS.
TreeFamTF316350.

Gene expression databases

ArrayExpressP18762.
BgeeP18762.
CleanExMM_ADRB2.
GenevestigatorP18762.

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. PTHR24248. 1 hit.
PTHR24248: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...

Other

NextBio279054.
PROP18762.
SOURCESearch...

Entry information

Entry nameADRB2_MOUSE
AccessionPrimary (citable) accession number: P18762
Secondary accession number(s): Q8BH38
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: July 27, 2011
Last modified: April 16, 2014
This is version 140 of the entry and version 2 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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries