UniProtKB - P18762 (ADRB2_MOUSE)
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Protein
Beta-2 adrenergic receptor
Gene
Adrb2
Organism
Mus musculus (Mouse)
Status
Functioni
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.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 113 | Agonist or antagonistBy similarity | 1 | |
Binding sitei | 118 | Agonist or antagonistBy similarity | 1 |
GO - Molecular functioni
- adenylate cyclase binding Source: BHF-UCL
- amyloid-beta binding Source: MGI
- beta2-adrenergic receptor activity Source: MGI
- enzyme binding Source: BHF-UCL
- epinephrine binding Source: GO_Central
- norepinephrine binding Source: HGNC
- potassium channel regulator activity Source: MGI
- protein complex binding Source: MGI
- protein homodimerization activity Source: HGNC
GO - Biological processi
- activation of adenylate cyclase activity Source: HGNC
- adenylate cyclase-activating adrenergic receptor signaling pathway Source: GO_Central
- adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: MGI
- adrenergic receptor signaling pathway Source: MGI
- bone resorption Source: MGI
- brown fat cell differentiation Source: MGI
- cell-cell signaling Source: GO_Central
- cellular response to amyloid-beta Source: ARUK-UCL
- desensitization of G-protein coupled receptor protein signaling pathway by arrestin Source: HGNC
- diet induced thermogenesis Source: MGI
- heat generation Source: MGI
- negative regulation of multicellular organism growth Source: MGI
- negative regulation of smooth muscle contraction Source: MGI
- norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure Source: MGI
- positive regulation of AMPA receptor activity Source: MGI
- positive regulation of autophagosome maturation Source: GO_Central
- positive regulation of bone mineralization Source: MGI
- positive regulation of lipophagy Source: GO_Central
- positive regulation of MAPK cascade Source: HGNC
- positive regulation of mini excitatory postsynaptic potential Source: ARUK-UCL
- positive regulation of protein kinase A signaling Source: ARUK-UCL
- positive regulation of protein serine/threonine kinase activity Source: MGI
- positive regulation of protein ubiquitination Source: MGI
- positive regulation of transcription by RNA polymerase II Source: MGI
- receptor-mediated endocytosis Source: HGNC
- regulation of sodium ion transport Source: MGI
- regulation of systemic arterial blood pressure by norepinephrine-epinephrine Source: MGI
- response to cold Source: MGI
Keywordsi
Molecular function | G-protein coupled receptor, Receptor, Transducer |
Enzyme and pathway databases
Reactomei | R-MMU-390696. Adrenoceptors. R-MMU-418555. G alpha (s) signalling events. R-MMU-5689880. Ub-specific processing proteases. R-MMU-8856825. Cargo recognition for clathrin-mediated endocytosis. R-MMU-8856828. Clathrin-mediated endocytosis. |
Names & Taxonomyi
Protein namesi | Recommended name: Beta-2 adrenergic receptorAlternative name(s): Beta-2 adrenoreceptor Short name: Beta-2 adrenoceptor |
Gene namesi | Name:Adrb2 Synonyms:Adrb2r |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:87938. Adrb2. |
Subcellular locationi
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 34 | ExtracellularBy similarityAdd BLAST | 34 | |
Transmembranei | 35 – 58 | Helical; Name=1By similarityAdd BLAST | 24 | |
Topological domaini | 59 – 71 | CytoplasmicBy similarityAdd BLAST | 13 | |
Transmembranei | 72 – 95 | Helical; Name=2By similarityAdd BLAST | 24 | |
Topological domaini | 96 – 106 | ExtracellularBy similarityAdd BLAST | 11 | |
Transmembranei | 107 – 129 | Helical; Name=3By similarityAdd BLAST | 23 | |
Topological domaini | 130 – 150 | CytoplasmicBy similarityAdd BLAST | 21 | |
Transmembranei | 151 – 174 | Helical; Name=4By similarityAdd BLAST | 24 | |
Topological domaini | 175 – 196 | ExtracellularBy similarityAdd BLAST | 22 | |
Transmembranei | 197 – 220 | Helical; Name=5By similarityAdd BLAST | 24 | |
Topological domaini | 221 – 274 | CytoplasmicBy similarityAdd BLAST | 54 | |
Transmembranei | 275 – 298 | Helical; Name=6By similarityAdd BLAST | 24 | |
Topological domaini | 299 – 305 | ExtracellularBy similarity | 7 | |
Transmembranei | 306 – 329 | Helical; Name=7By similarityAdd BLAST | 24 | |
Topological domaini | 330 – 418 | CytoplasmicBy similarityAdd BLAST | 89 |
Keywords - Cellular componenti
Cell membrane, Endosome, MembranePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000069134 | 1 – 418 | Beta-2 adrenergic receptorAdd BLAST | 418 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 6 | N-linked (GlcNAc...) asparagineCurated | 1 | |
Glycosylationi | 15 | N-linked (GlcNAc...) asparagineCurated | 1 | |
Disulfide bondi | 106 ↔ 191 | PROSITE-ProRule annotation | ||
Modified residuei | 141 | PhosphotyrosineBy similarity | 1 | |
Disulfide bondi | 184 ↔ 190 | PROSITE-ProRule annotation | ||
Modified residuei | 246 | PhosphoserineBy similarity | 1 | |
Modified residuei | 261 | Phosphoserine; by PKASequence analysis | 1 | |
Modified residuei | 262 | Phosphoserine; by PKASequence analysis | 1 | |
Lipidationi | 341 | S-palmitoyl cysteineBy similarity | 1 | |
Modified residuei | 345 | Phosphoserine; by PKABy similarity | 1 | |
Modified residuei | 346 | Phosphoserine; by PKABy similarity | 1 | |
Modified residuei | 355 | Phosphoserine; by BARKCurated | 1 | |
Modified residuei | 356 | Phosphoserine; by BARKCurated | 1 | |
Modified residuei | 387 | 4-hydroxyprolineBy similarity | 1 | |
Modified residuei | 400 | 4-hydroxyprolineBy similarity | 1 |
Post-translational modificationi
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).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).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
Keywords - PTMi
Disulfide bond, Glycoprotein, Hydroxylation, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugationProteomic databases
PaxDbi | P18762. |
PRIDEi | P18762. |
PTM databases
iPTMneti | P18762. |
PhosphoSitePlusi | P18762. |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000045730. |
CleanExi | MM_ADRB2. |
Genevisiblei | P18762. MM. |
Interactioni
Subunit structurei
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. Interacts with CNIH4. Interacts with ARRDC3.By similarity
Binary interactionsi
GO - Molecular functioni
- adenylate cyclase binding Source: BHF-UCL
- enzyme binding Source: BHF-UCL
- protein complex binding Source: MGI
- protein homodimerization activity Source: HGNC
Protein-protein interaction databases
CORUMi | P18762. |
DIPi | DIP-59568N. |
IntActi | P18762. 9 interactors. |
MINTi | P18762. |
STRINGi | 10090.ENSMUSP00000062256. |
Chemistry databases
BindingDBi | P18762. |
Structurei
3D structure databases
ProteinModelPortali | P18762. |
SMRi | P18762. |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 193 – 207 | Agonist and antagonist bindingBy similarityAdd BLAST | 15 | |
Regioni | 286 – 293 | Agonist and antagonist bindingBy similarity | 8 | |
Regioni | 312 – 316 | Agonist and antagonist bindingBy similarity | 5 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 415 – 418 | PDZ-binding | 4 |
Sequence similaritiesi
Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB2 sub-subfamily.PROSITE-ProRule annotation
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3656. Eukaryota. ENOG410XRW9. LUCA. |
GeneTreei | ENSGT00890000139331. |
HOGENOMi | HOG000239242. |
HOVERGENi | HBG106962. |
InParanoidi | P18762. |
KOi | K04142. |
OMAi | GRFHAQN. |
OrthoDBi | EOG091G06VI. |
TreeFami | TF316350. |
Family and domain databases
CDDi | cd15957. 7tmA_Beta2_AR. 1 hit. |
InterProi | View protein in InterPro IPR002233. ADR_fam. IPR000332. ADRB2_rcpt. IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. |
PANTHERi | PTHR24248:SF21. PTHR24248:SF21. 1 hit. |
Pfami | View protein in Pfam PF00001. 7tm_1. 1 hit. |
PRINTSi | PR01103. ADRENERGICR. PR00562. ADRENRGCB2AR. PR00237. GPCRRHODOPSN. |
SMARTi | View protein in SMART SM01381. 7TM_GPCR_Srsx. 1 hit. |
PROSITEi | View protein in PROSITE PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. |
i Sequence
Sequence statusi: Complete.
P18762-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MGPHGNDSDF LLAPNGSRAP DHDVTQERDE AWVVGMAILM SVIVLAIVFG
60 70 80 90 100
NVLVITAIAK FERLQTVTNY FIISLACADL VMGLAVVPFG ASHILMKMWN
110 120 130 140 150
FGNFWCEFWT SIDVLCVTAS IETLCVIAVD RYVAITSPFK YQSLLTKNKA
160 170 180 190 200
RVVILMVWIV SGLTSFLPIQ MHWYRATHKK AIDCYTEETC CDFFTNQAYA
210 220 230 240 250
IASSIVSFYV PLVVMVFVYS RVFQVAKRQL QKIDKSEGRF HAQNLSQVEQ
260 270 280 290 300
DGRSGHGLRR SSKFCLKEHK ALKTLGIIMG TFTLCWLPFF IVNIVHVIRD
310 320 330 340 350
NLIPKEVYIL LNWLGYVNSA FNPLIYCRSP DFRIAFQELL CLRRSSSKTY
360 370 380 390 400
GNGYSSNSNG RTDYTGEPNT CQLGQEREQE LLCEDPPGME GFVNCQGTVP
410
SLSVDSQGRN CSTNDSPL
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 21 | D → H in CAA33664 (PubMed:2549959).Curated | 1 | |
Sequence conflicti | 94 – 95 | IL → TS in CAA33664 (PubMed:2549959).Curated | 2 | |
Sequence conflicti | 254 | S → T in CAA33664 (PubMed:2549959).Curated | 1 | |
Sequence conflicti | 347 – 348 | SK → FE in CAA33664 (PubMed:2549959).Curated | 2 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X15643 Genomic DNA. Translation: CAA33664.1. AK080241 mRNA. Translation: BAC37856.1. CH466528 Genomic DNA. Translation: EDL09746.1. BC032883 mRNA. Translation: AAH32883.1. |
CCDSi | CCDS29289.1. |
PIRi | S00260. |
RefSeqi | NP_031446.2. NM_007420.3. |
UniGenei | Mm.5598. |
Genome annotation databases
Ensembli | ENSMUST00000053640; ENSMUSP00000062256; ENSMUSG00000045730. |
GeneIDi | 11555. |
KEGGi | mmu:11555. |
UCSCi | uc008fcy.2. mouse. |
Similar proteinsi
Entry informationi
Entry namei | ADRB2_MOUSE | |
Accessioni | P18762Primary (citable) accession number: P18762 Secondary accession number(s): Q8BH38 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1990 |
Last sequence update: | July 27, 2011 | |
Last modified: | March 28, 2018 | |
This is version 177 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |