ADRB2_CANLF
ID ADRB2_CANLF Reviewed; 415 AA.
AC P54833;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Beta-2 adrenergic receptor;
DE AltName: Full=Beta-2 adrenoreceptor;
DE Short=Beta-2 adrenoceptor;
GN Name=ADRB2;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart muscle;
RX PubMed=8880434; DOI=10.2527/1996.7492285x;
RA Emala C.W., Kuhl J., Hirshman C.A., Levine M.A.;
RT "Rapid communication: cloning and sequencing of a canine beta 2-adrenergic
RT receptor cDNA.";
RL J. Anim. Sci. 74:2285-2286(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=9220370; DOI=10.3109/10799899709039152;
RA Huang R.-R.C., Rapoport D., Schaeffer M.-T., Cascieri M.A., Fong T.M.;
RT "Molecular cloning of the dog beta 1 and beta 2 adrenergic receptors.";
RL J. Recept. Signal Transduct. 17:599-607(1997).
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:9220370}.
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:0000250|UniProtKB:P07550};
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.
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; X94608; CAA64316.1; -; mRNA.
DR EMBL; U73206; AAB93647.1; -; Genomic_DNA.
DR RefSeq; NP_001003234.1; NM_001003234.1.
DR AlphaFoldDB; P54833; -.
DR SMR; P54833; -.
DR STRING; 9612.ENSCAFP00000027094; -.
DR BindingDB; P54833; -.
DR ChEMBL; CHEMBL2289; -.
DR DrugCentral; P54833; -.
DR PaxDb; P54833; -.
DR PRIDE; P54833; -.
DR GeneID; 403910; -.
DR KEGG; cfa:403910; -.
DR CTD; 154; -.
DR eggNOG; KOG3656; Eukaryota.
DR InParanoid; P54833; -.
DR OrthoDB; 614199at2759; -.
DR PRO; PR:P54833; -.
DR Proteomes; UP000002254; Unplaced.
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; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; ISS:HGNC-UCL.
DR GO; GO:0004941; F:beta2-adrenergic receptor activity; ISS:HGNC-UCL.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0051380; F:norepinephrine binding; ISS:HGNC-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:HGNC-UCL.
DR GO; GO:0007190; P:activation of adenylate cyclase activity; ISS:HGNC-UCL.
DR GO; GO:0071880; P:adenylate cyclase-activating adrenergic receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0002032; P:desensitization of G protein-coupled receptor signaling pathway by arrestin; ISS:HGNC-UCL.
DR GO; GO:0045986; P:negative regulation of smooth muscle contraction; IBA:GO_Central.
DR GO; GO:0002025; P:norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure; IBA:GO_Central.
DR GO; GO:1901098; P:positive regulation of autophagosome maturation; ISS:GO_Central.
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:0006898; P:receptor-mediated endocytosis; ISS:HGNC-UCL.
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 2: Evidence at transcript 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..415
FT /note="Beta-2 adrenergic receptor"
FT /id="PRO_0000069128"
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..415
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 379..415
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 412..415
FT /note="PDZ-binding"
FT COMPBIAS 393..415
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 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 387
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250"
FT MOD_RES 397
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 /evidence="ECO:0000255"
FT CARBOHYD 15
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 415 AA; 46589 MW; 392588623833445E CRC64;
MGQPANRSVF LLAPNGSHAP DQGDSQERSE AWVVGMGIVM SLIVLAIVFG NVLVITAIAR
FERLQTVTNY FITSLACADL VMGLAVVPFG ASHILMKMWT FGNFWCEFWT SIDVLCVTAS
IETLCVIAVD RYFAITSPFK YQSLLTKNKA RVVILMVWIV SGLTSFLPIQ MHWYRATHQE
AINCYAKETC CDFFTNQAYA IASSIVSFYL PLVVMVFVYS RVFQVAQRQL QKIDRSEGRF
HAQNLSQVEQ DGRSGHGHRR SSKFCLKEHK ALKTLGIIMG TFTLCWLPFF IVNIVHVIQD
NLIPKEVYIL LNWVGYVNSA FNPLIYCRSP DFRIAFQELL CLRRSSLKAY GNGYSNNSNS
RSDYAGEHSG CHLGQEKDSE LLCEDPPGTE DRQGTVPSDS VDSQGRNCST NDSLL
