ADRB2_BOVIN
ID ADRB2_BOVIN Reviewed; 418 AA.
AC Q28044; Q29RK5;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Beta-2 adrenergic receptor;
DE AltName: Full=Beta-2 adrenoreceptor;
DE Short=Beta-2 adrenoceptor;
GN Name=ADRB2;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=Fleckvieh; TISSUE=Oviduct;
RX PubMed=10342858; DOI=10.1210/endo.140.6.6701;
RA Einspanier R., Gabler C., Kettler A., Kloas W.;
RT "Characterization and localization of beta2-adrenergic receptors in the
RT bovine oviduct: indication for progesterone-mediated expression.";
RL Endocrinology 140:2679-2684(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Hypothalamus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 253-377.
RA Stoffel B., Hagen-Mann K., Mann W., Meyer H.H.D.;
RL Submitted (JAN-1993) to the EMBL/GenBank/DDBJ databases.
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 (By similarity).
CC {ECO:0000250|UniProtKB:P07550}.
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 -!- TISSUE SPECIFICITY: Expressed in oviduct epithelial cells with high
CC levels during the luteal phase of the sexual cycle. Lower levels around
CC ovulation. Also expressed in liver. {ECO:0000269|PubMed:10342858}.
CC -!- INDUCTION: 50% increase with progesterone treatment in cultured oviduct
CC epithelial cells. {ECO:0000269|PubMed:10342858}.
CC -!- PTM: Palmitoylated (By similarity); may reduce accessibility of Ser-345
CC and Ser-346 by anchoring Cys-341 to the plasma membrane. Agonist
CC stimulation promotes depalmitoylation and further allows Ser-345 and
CC Ser-346 phosphorylation (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. Could be
CC depalmitoylated by LYPLA1 at the plasma membrane.
CC {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; Z86037; CAB06661.1; -; mRNA.
DR EMBL; BC114132; AAI14133.1; -; mRNA.
DR EMBL; X67213; CAA47653.1; -; mRNA.
DR PIR; S31617; S31617.
DR RefSeq; NP_776656.1; NM_174231.1.
DR AlphaFoldDB; Q28044; -.
DR SMR; Q28044; -.
DR STRING; 9913.ENSBTAP00000002779; -.
DR BindingDB; Q28044; -.
DR ChEMBL; CHEMBL3373; -.
DR DrugCentral; Q28044; -.
DR PaxDb; Q28044; -.
DR PRIDE; Q28044; -.
DR Ensembl; ENSBTAT00000002779; ENSBTAP00000002779; ENSBTAG00000002144.
DR GeneID; 281605; -.
DR KEGG; bta:281605; -.
DR CTD; 154; -.
DR VEuPathDB; HostDB:ENSBTAG00000002144; -.
DR VGNC; VGNC:25697; ADRB2.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000159538; -.
DR HOGENOM; CLU_009579_11_0_1; -.
DR InParanoid; Q28044; -.
DR OMA; RFHNQNN; -.
DR OrthoDB; 614199at2759; -.
DR TreeFam; TF316350; -.
DR Reactome; R-BTA-390696; Adrenoceptors.
DR Reactome; R-BTA-418555; G alpha (s) signalling events.
DR Reactome; R-BTA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR PRO; PR:Q28044; -.
DR Proteomes; UP000009136; Chromosome 7.
DR Bgee; ENSBTAG00000002144; Expressed in gluteus medius and 100 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; IBA:GO_Central.
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:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
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:0071880; P:adenylate cyclase-activating adrenergic receptor signaling pathway; IBA:GO_Central.
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; 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: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 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..418
FT /note="Beta-2 adrenergic receptor"
FT /id="PRO_0000069127"
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 398..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 246
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07550"
FT MOD_RES 261
FT /note="Phosphothreonine; 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 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"
FT CONFLICT 254
FT /note="S -> T (in Ref. 3; CAA47653)"
FT /evidence="ECO:0000305"
FT CONFLICT 272
FT /note="L -> P (in Ref. 3; CAA47653)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 418 AA; 47136 MW; CAB2A18470A801B0 CRC64;
MGQPGNRSVF LLAPNASHAP DQNVTLERDE AWVVGMGILM SLIVLAIVFG NVLVITAIAK
FERLQTVTNY FITSLACADL VMGLAVVPFG ACHILMKMWT FGNFWCEFWT SIDVLCVTAS
IETLCVIAVD RYLAITSPFK YQCLLTKNKA RVVILMVWIV SGLTSFLPIQ MHWYRASHKE
AINCYAKETC CDFFTNQPYA IASSIVSFYL PLVVMVFVYS RVFQVAKRQL QKIDKSEGRF
HAQNVSQVEQ DGRSGLGQRR TSKFYLKEHK ALKTLGIIMG TFTLCWLPFF IVNIVHVIKD
NLIRKEIYIL LNWLGYINSA FNPLIYCRSP DFRIAFQELL CLRRSSLKAY GNGCSSNSND
RTDYTGEQSG YHLGEEKDSE LLCEDPPGTE NFVNQQGTVP SDSIDSQGRN CSTNDSLL
