ADRB2_MESAU
ID ADRB2_MESAU Reviewed; 418 AA.
AC P04274;
DT 20-MAR-1987, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-1987, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Beta-2 adrenergic receptor;
DE AltName: Full=Beta-2 adrenoreceptor;
DE Short=Beta-2 adrenoceptor;
GN Name=ADRB2;
OS Mesocricetus auratus (Golden hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Mesocricetus.
OX NCBI_TaxID=10036;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RX PubMed=3010132; DOI=10.1038/321075a0;
RA Dixon R.A.F., Kobilka B.K., Strader D.J., Benovic J.L., Dohlman H.G.,
RA Frielle T., Bolanowski M.A., Bennett C.D., Rands E., Diehl R.E.,
RA Mumford R.A., Slater E.E., Sigal I.S., Caron M.G., Lefkowitz R.J.,
RA Strader C.D.;
RT "Cloning of the gene and cDNA for mammalian beta-adrenergic receptor and
RT homology with rhodopsin.";
RL Nature 321:75-79(1986).
RN [2]
RP MUTAGENESIS TO CONFIRM GLYCOSYLATION SITES.
RX PubMed=2162359; DOI=10.1016/s0021-9258(18)87012-0;
RA Rands E., Candelore M.R., Cheung A.H., Will W.S., Strader C.D.,
RA Dixon R.A.F.;
RT "Mutational analysis of beta-adrenergic receptor glycosylation.";
RL J. Biol. Chem. 265:10759-10764(1990).
RN [3]
RP MUTAGENESIS OF SER-204 AND SER-207, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=2547766; DOI=10.1016/s0021-9258(18)80035-7;
RA Strader C.D., Candelore M.R., Hill W.S., Sigal I.S., Dixon R.A.F.;
RT "Identification of two serine residues involved in agonist activation of
RT the beta-adrenergic receptor.";
RL J. Biol. Chem. 264:13572-13578(1989).
RN [4]
RP MUTAGENESIS OF ASP-79 AND ASP-113.
RX PubMed=2899076; DOI=10.1016/s0021-9258(19)81509-0;
RA Strader C.D., Sigal I.S., Candelore M.R., Rands E., Hill W.S.,
RA Dixon R.A.F.;
RT "Conserved aspartic acid residues 79 and 113 of the beta-adrenergic
RT receptor have different roles in receptor function.";
RL J. Biol. Chem. 263:10267-10271(1988).
RN [5]
RP 3D-STRUCTURE MODELING.
RX PubMed=1318386; DOI=10.1016/0022-2836(92)90406-a;
RA Huss K.M., Lybrand T.P.;
RT "Three-dimensional structure for the beta 2 adrenergic receptor protein
RT based on computer modeling studies.";
RL J. Mol. Biol. 225:859-871(1992).
CC -!- FUNCTION: Beta-adrenergic receptors mediate the catecholamine-induced
CC activation of adenylate cyclase through the action of G proteins. The
CC beta-2-adrenergic receptor binds epinephrine with an approximately 30-
CC fold greater affinity than it does norepinephrine.
CC {ECO:0000269|PubMed:2547766}.
CC -!- SUBUNIT: Binds SLC9A3R1 and GPRASP1. Interacts with ARRB1 and ARRB2.
CC Interacts with SRC (By similarity). Interacts with USP20 and USP33 (By
CC similarity). Interacts with VHL; the interaction, which is increased on
CC hydroxylation of ADRB2, ubiquitinates ADRB2 leading to its degradation.
CC Interacts with EGLN3; the interaction hydroxylates ADRB2 facilitating
CC VHL-E3 ligase-mediated ubiquitination. Interacts (via PDZ-binding
CC motif) with SNX27 (via PDZ domain); the interaction is required when
CC endocytosed to prevent degradation in lysosomes and promote recycling
CC to the plasma membrane. Interacts with CNIH4. Interacts with ARRDC3.
CC Interacts with NEDD4 (By similarity). Interacts with MARCHF2 (By
CC similarity). {ECO:0000250|UniProtKB:P07550}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:2547766};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P07550}. Early
CC endosome {ECO:0000250|UniProtKB:P07550}. Golgi apparatus
CC {ECO:0000250|UniProtKB:P07550}. Note=Colocalizes with VHL at the cell
CC membrane. Activated receptors are internalized into endosomes prior to
CC their degradation in lysosomes. Activated receptors are also detected
CC within the Golgi apparatus. {ECO:0000250|UniProtKB:P07550}.
CC -!- PTM: Palmitoylated; may reduce accessibility of Ser-345 and Ser-346 by
CC anchoring Cys-341 to the plasma membrane. Agonist stimulation promotes
CC depalmitoylation and further allows Ser-345 and Ser-346 phosphorylation
CC (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated by PKA and BARK upon agonist stimulation, which
CC mediates homologous desensitization of the receptor. PKA-mediated
CC phosphorylation seems to facilitate phosphorylation by BARK (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylation of Tyr-141 is induced by insulin and leads to
CC supersensitization of the receptor. {ECO:0000250}.
CC -!- PTM: Polyubiquitinated. Agonist-induced ubiquitination leads to sort
CC internalized receptors to the lysosomes for degradation.
CC Deubiquitination by USP20 and USP33, leads to ADRB2 recycling and
CC resensitization after prolonged agonist stimulation. USP20 and USP33
CC are constitutively associated and are dissociated immediately after
CC agonist stimulation. Ubiquitination by the VHL-E3 ligase complex is
CC oxygen-dependent (By similarity). {ECO:0000250}.
CC -!- PTM: Hydroxylation by EGLN3 occurs only under normoxia and increases
CC the interaction with VHL and the subsequent ubiquitination and
CC degradation of ADRB2. {ECO:0000250}.
CC -!- PTM: Palmitoylated. Mainly palmitoylated at Cys-341. Palmitoylation may
CC reduce accessibility of phosphorylation sites by anchoring the receptor
CC to the plasma membrane. Agonist stimulation promotes depalmitoylation
CC and further allows Ser-345 and Ser-346 phosphorylation. Also undergoes
CC transient, ligand-induced palmitoylation at Cys-265 probably by ZDHHC9,
CC ZDHHC14 and ZDHHC18 within the Golgi. Palmitoylation at Cys-265
CC requires phosphorylation by PKA and receptor internalization and
CC stabilizes the receptor. Could be depalmitoylated by LYPLA1 at the
CC plasma membrane. {ECO:0000250|UniProtKB:P07550}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC Adrenergic receptor subfamily. ADRB2 sub-subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; X03804; CAA27430.1; -; mRNA.
DR RefSeq; NP_001268877.1; NM_001281948.1.
DR AlphaFoldDB; P04274; -.
DR SMR; P04274; -.
DR ELM; P04274; -.
DR STRING; 10036.XP_005074729.1; -.
DR ChEMBL; CHEMBL5943; -.
DR DrugCentral; P04274; -.
DR iPTMnet; P04274; -.
DR GeneID; 101836719; -.
DR CTD; 154; -.
DR eggNOG; KOG3656; Eukaryota.
DR OrthoDB; 614199at2759; -.
DR PRO; PR:P04274; -.
DR Proteomes; UP000189706; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0043235; C:receptor complex; ISS:HGNC-UCL.
DR GO; GO:0008179; F:adenylate cyclase binding; IEA:Ensembl.
DR GO; GO:0001540; F:amyloid-beta binding; IEA:Ensembl.
DR GO; GO:0004941; F:beta2-adrenergic receptor activity; ISS:HGNC-UCL.
DR GO; GO:0051380; F:norepinephrine binding; ISS:HGNC-UCL.
DR GO; GO:0015459; F:potassium channel regulator activity; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:HGNC-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0007190; P:activation of adenylate cyclase activity; ISS:HGNC-UCL.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0045453; P:bone resorption; IEA:Ensembl.
DR GO; GO:0050873; P:brown fat cell differentiation; IEA:Ensembl.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IEA:Ensembl.
DR GO; GO:0002032; P:desensitization of G protein-coupled receptor signaling pathway by arrestin; ISS:HGNC-UCL.
DR GO; GO:0002024; P:diet induced thermogenesis; IEA:Ensembl.
DR GO; GO:0031649; P:heat generation; IEA:Ensembl.
DR GO; GO:0040015; P:negative regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0045986; P:negative regulation of smooth muscle contraction; IEA:Ensembl.
DR GO; GO:0002025; P:norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure; IEA:Ensembl.
DR GO; GO:2000969; P:positive regulation of AMPA receptor activity; IEA:Ensembl.
DR GO; GO:1901098; P:positive regulation of autophagosome maturation; ISS:GO_Central.
DR GO; GO:0030501; P:positive regulation of bone mineralization; IEA:Ensembl.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IEA:Ensembl.
DR GO; GO:1904504; P:positive regulation of lipophagy; ISS:GO_Central.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:HGNC-UCL.
DR GO; GO:0061885; P:positive regulation of mini excitatory postsynaptic potential; IEA:Ensembl.
DR GO; GO:0010739; P:positive regulation of protein kinase A signaling; IEA:Ensembl.
DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0006898; P:receptor-mediated endocytosis; ISS:HGNC-UCL.
DR GO; GO:0002028; P:regulation of sodium ion transport; IEA:Ensembl.
DR GO; GO:0009409; P:response to cold; IEA:Ensembl.
DR GO; GO:0006939; P:smooth muscle contraction; IEA:Ensembl.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR InterPro; IPR002233; ADR_fam.
DR InterPro; IPR000332; ADRB2_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR24248:SF21; PTHR24248:SF21; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR01103; ADRENERGICR.
DR PRINTS; PR00562; ADRENRGCB2AR.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR SMART; SM01381; 7TM_GPCR_Srsx; 1.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Endosome; G-protein coupled receptor;
KW Glycoprotein; Golgi apparatus; Hydroxylation; Lipoprotein; Membrane;
KW Palmitate; Phosphoprotein; Receptor; Reference proteome; Transducer;
KW Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..418
FT /note="Beta-2 adrenergic receptor"
FT /id="PRO_0000069133"
FT TOPO_DOM 1..34
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 35..58
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 59..71
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 72..95
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 96..106
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 107..129
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250"
FT TOPO_DOM 130..150
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 151..174
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250"
FT TOPO_DOM 175..196
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 197..220
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250"
FT TOPO_DOM 221..274
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 275..298
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250"
FT TOPO_DOM 299..305
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 306..329
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250"
FT TOPO_DOM 330..418
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 394..418
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 415..418
FT /note="PDZ-binding"
FT MOD_RES 141
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P07550"
FT MOD_RES 261
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000255"
FT MOD_RES 262
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000255"
FT MOD_RES 345
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P07550"
FT MOD_RES 346
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P07550"
FT MOD_RES 355
FT /note="Phosphoserine; by BARK"
FT /evidence="ECO:0000305"
FT MOD_RES 356
FT /note="Phosphoserine; by BARK"
FT /evidence="ECO:0000305"
FT MOD_RES 387
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250"
FT MOD_RES 400
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250"
FT LIPID 265
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P07550"
FT LIPID 341
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P07550"
FT CARBOHYD 6
FT /note="N-linked (GlcNAc...) asparagine"
FT CARBOHYD 15
FT /note="N-linked (GlcNAc...) asparagine"
FT DISULFID 106..191
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 184..190
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT MUTAGEN 79
FT /note="D->A: Small decrease in agonist binding. No effect
FT on antagonist binding."
FT /evidence="ECO:0000269|PubMed:2899076"
FT MUTAGEN 113
FT /note="D->A: Drastic decrease in agonist and antagonist
FT binding. Stimulates adenylyl cyclase activity."
FT /evidence="ECO:0000269|PubMed:2899076"
FT MUTAGEN 204
FT /note="S->A: Decrease in catechol agonist binding."
FT /evidence="ECO:0000269|PubMed:2547766"
FT MUTAGEN 207
FT /note="S->A: Decrease in catechol agonist binding."
FT /evidence="ECO:0000269|PubMed:2547766"
SQ SEQUENCE 418 AA; 46861 MW; 9B20478F91FB284E CRC64;
MGPPGNDSDF LLTTNGSHVP DHDVTEERDE AWVVGMAILM SVIVLAIVFG NVLVITAIAK
FERLQTVTNY FITSLACADL VMGLAVVPFG ASHILMKMWN FGNFWCEFWT SIDVLCVTAS
IETLCVIAVD RYIAITSPFK YQSLLTKNKA RMVILMVWIV SGLTSFLPIQ MHWYRATHQK
AIDCYHKETC CDFFTNQAYA IASSIVSFYV PLVVMVFVYS RVFQVAKRQL QKIDKSEGRF
HSPNLGQVEQ DGRSGHGLRR SSKFCLKEHK ALKTLGIIMG TFTLCWLPFF IVNIVHVIQD
NLIPKEVYIL LNWLGYVNSA FNPLIYCRSP DFRIAFQELL CLRRSSSKAY GNGYSSNSNG
KTDYMGEASG CQLGQEKESE RLCEDPPGTE SFVNCQGTVP SLSLDSQGRN CSTNDSPL
