ADRB2_CAVPO
ID ADRB2_CAVPO Reviewed; 418 AA.
AC Q8K4Z4;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Beta-2 adrenergic receptor;
DE AltName: Full=Beta-2 adrenoreceptor;
DE Short=Beta-2 adrenoceptor;
GN Name=Adrb2;
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=Dunkin-Hartley;
RX PubMed=12460637; DOI=10.1016/s0014-2999(02)02692-4;
RA Oostendorp J., Meurs H., Nelemans S.A., Zaagsma J., Kauffman H.F.,
RA Postma D.S., Boddeke H.W.G.M., Biber K.;
RT "Cloning, pharmacological characterization, and polymorphism screening of
RT the guinea pig beta(2)-adrenoceptor.";
RL Eur. J. Pharmacol. 457:1-10(2002).
CC -!- FUNCTION: Beta-adrenergic receptors mediate the catecholamine-induced
CC activation of adenylate cyclase through the action of G proteins.
CC {ECO:0000269|PubMed:12460637}.
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:12460637};
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: 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.
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 phosphorylation. Could be depalmitoylated by LYPLA1
CC at the 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; AJ459814; CAD30869.1; -; Genomic_DNA.
DR RefSeq; XP_003477383.1; XM_003477335.3.
DR AlphaFoldDB; Q8K4Z4; -.
DR SMR; Q8K4Z4; -.
DR STRING; 10141.ENSCPOP00000018242; -.
DR BindingDB; Q8K4Z4; -.
DR ChEMBL; CHEMBL5414; -.
DR DrugCentral; Q8K4Z4; -.
DR Ensembl; ENSCPOT00000012875; ENSCPOP00000018242; ENSCPOG00000012753.
DR GeneID; 100722663; -.
DR KEGG; cpoc:100722663; -.
DR CTD; 154; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000159538; -.
DR HOGENOM; CLU_009579_11_0_1; -.
DR InParanoid; Q8K4Z4; -.
DR OMA; RFHNQNN; -.
DR OrthoDB; 614199at2759; -.
DR TreeFam; TF316350; -.
DR PRO; PR:Q8K4Z4; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR Bgee; ENSCPOG00000012753; Expressed in liver and 12 other tissues.
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 3: Inferred from homology;
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_0000305175"
FT TOPO_DOM 1..37
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 38..58
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 59..70
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 71..91
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 92..107
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 108..128
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250"
FT TOPO_DOM 129..151
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 152..172
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250"
FT TOPO_DOM 173..197
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 198..218
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250"
FT TOPO_DOM 219..274
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 275..295
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250"
FT TOPO_DOM 296..306
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 307..327
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250"
FT TOPO_DOM 328..418
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 389..418
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 415..418
FT /note="PDZ-binding"
FT COMPBIAS 399..418
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 141
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P07550"
FT MOD_RES 246
FT /note="Phosphoserine"
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 355
FT /note="Phosphoserine; by BARK"
FT /evidence="ECO:0000250"
FT MOD_RES 356
FT /note="Phosphoserine; by BARK"
FT /evidence="ECO:0000250"
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 341
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P07550"
FT CARBOHYD 6
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 15
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 23
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 106..191
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 184..190
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
SQ SEQUENCE 418 AA; 46991 MW; 1090D41C96F00E50 CRC64;
MGHLGNGSDF LLAPNASHAP DHNVTRERDE AWVVGMAIVM SLIVLAIVFG NVLVITAIAK
FERLQTVTNY FITSLACADL VMGLAVVPFG ASHILMNMWT FGNFWCEFWT SIDVLCVTAS
IETLCVIAVD RYFAITSPFK YQSLLTKNKA RVVILMVWVV SGLTSFLPIQ MHWYRATHKD
AINCYAEETC CDFFTNQAYA IASSIVSFYL PLVVMVFVYS RVFQVAKKQL QKIDRSEGRF
HTQNLSQVEQ DGRSGHGLRR SSKFYLKEHK ALKTLGIIMG TFTLCWLPFF IVNIVHVIQD
NLIPKEVYIL LNWVGYVNSA FNPLIYCRSP DFRIAFQELL CLRRSALKAY GNDCSSNSNG
KTDYTGEPNV CHQGQEKERE LLCEDPPGTE DLVSCPGTVP SDSIDSQGRN YSTNDSLL
