P18762 (ADRB2_MOUSE) 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

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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. 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 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 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_component	apical 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_function	adenylate 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 binding Inferred from physical interaction PubMed 9235896. Source: MGI 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_0000069134
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
	Motif	415 – 418	4	PDZ-binding
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	21	1	D → H in CAA33664. Ref.2
	Sequence conflict	94 – 95	2	IL → TS in CAA33664. Ref.2
	Sequence conflict	254	1	S → T in CAA33664. Ref.2
	Sequence conflict	347 – 348	2	SK → FE in CAA33664. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P18762 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 51D1EC73D7619D58	FASTA	418	46,998
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
CCDS	CCDS29289.1.
PIR	S00260.
RefSeq	NP_031446.2. NM_007420.3.
UniGene	Mm.5598.
3D structure databases
ProteinModelPortal	P18762.
SMR	P18762. Positions 7-342.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
DIP	DIP-59568N.
IntAct	P18762. 5 interactions.
MINT	MINT-1793203.
Chemistry
BindingDB	P18762.
ChEMBL	CHEMBL2111395.
GuidetoPHARMACOLOGY	29.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P18762.
Proteomic databases
PRIDE	P18762.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000053640; ENSMUSP00000062256; ENSMUSG00000045730.
GeneID	11555.
KEGG	mmu:11555.
UCSC	uc008fcy.1. mouse.
Organism-specific databases
CTD	154.
MGI	MGI:87938. Adrb2.
Phylogenomic databases
eggNOG	NOG262978.
GeneTree	ENSGT00720000108411.
HOGENOM	HOG000239242.
HOVERGEN	HBG106962.
InParanoid	Q8BH38.
KO	K04142.
OMA	RVFQVAK.
OrthoDB	EOG7BS4BS.
TreeFam	TF316350.
Gene expression databases
ArrayExpress	P18762.
Bgee	P18762.
CleanEx	MM_ADRB2.
Genevestigator	P18762.
Family and domain databases
Gene3D	1.20.1070.10. 1 hit.
InterPro	IPR002233. ADR_fam. IPR000332. ADRB2_rcpt. IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. [Graphical view]
PANTHER	PTHR24248:SF21. PTHR24248:SF21. 1 hit.
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
NextBio	279054.
PRO	P18762.
SOURCE	Search...

Entry information

Entry name

ADRB2_MOUSE

Accession

Primary (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:	July 9, 2014
This is version 143 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program