ADRB2_PIG
ID ADRB2_PIG Reviewed; 418 AA.
AC Q28997; O02779; Q6QTF6;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 25-MAY-2022, entry version 144.
DE RecName: Full=Beta-2 adrenergic receptor;
DE AltName: Full=Beta-2 adrenoreceptor;
DE Short=Beta-2 adrenoceptor;
GN Name=ADRB2;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Blood;
RA Liang W., Bidwell C.A., Williams S.K., Mills S.E.;
RT "Molecular cloning of the porcine beta-2-adrenergic receptor gene.";
RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Li W.F., Nie C., Zhou X.X., Lu P., Yao J.T., Feng J.;
RT "Molecular cloning of the porcine beta-2-adrenergic receptor gene.";
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 144-252, AND TISSUE SPECIFICITY.
RX PubMed=10229356; DOI=10.2527/1999.773611x;
RA McNeel R.L., Mersmann H.J.;
RT "Distribution and quantification of beta1-, beta2-, and beta3-adrenergic
RT receptor subtype transcripts in porcine tissues.";
RL J. Anim. Sci. 77:611-621(1999).
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 heart, liver, lung, skeletal muscle
CC and subcutaneous adipose tissue. {ECO:0000269|PubMed:10229356}.
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; AF000134; AAB58713.1; -; Genomic_DNA.
DR EMBL; AY526088; AAS18308.1; -; Genomic_DNA.
DR EMBL; U53185; AAB01978.1; -; mRNA.
DR RefSeq; NP_001121908.1; NM_001128436.1.
DR AlphaFoldDB; Q28997; -.
DR SMR; Q28997; -.
DR ChEMBL; CHEMBL3801; -.
DR PRIDE; Q28997; -.
DR GeneID; 397357; -.
DR KEGG; ssc:397357; -.
DR CTD; 154; -.
DR InParanoid; Q28997; -.
DR PRO; PR:Q28997; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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: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:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IEA:InterPro.
DR GO; GO:0097746; P:blood vessel diameter maintenance; IEA:InterPro.
DR GO; GO:0002032; P:desensitization of G protein-coupled receptor signaling pathway by arrestin; ISS:HGNC-UCL.
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 GO; GO:0006940; P:regulation of smooth muscle contraction; IEA:InterPro.
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_0000069135"
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 381..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 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 /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"
FT CONFLICT 152
FT /note="V -> M (in Ref. 3; AAB01978)"
FT /evidence="ECO:0000305"
FT CONFLICT 159
FT /note="V -> I (in Ref. 3; AAB01978)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="I -> T (in Ref. 3; AAB01978)"
FT /evidence="ECO:0000305"
FT CONFLICT 170
FT /note="K -> Q (in Ref. 3; AAB01978)"
FT /evidence="ECO:0000305"
FT CONFLICT 175
FT /note="Q -> R (in Ref. 3; AAB01978)"
FT /evidence="ECO:0000305"
FT CONFLICT 179..189
FT /note="REALNCYAEEA -> QKAIDCYHKET (in Ref. 3; AAB01978)"
FT /evidence="ECO:0000305"
FT CONFLICT 198
FT /note="P -> A (in Ref. 3; AAB01978)"
FT /evidence="ECO:0000305"
FT CONFLICT 210
FT /note="L -> V (in Ref. 3; AAB01978)"
FT /evidence="ECO:0000305"
FT CONFLICT 227
FT /note="R -> K (in Ref. 3; AAB01978)"
FT /evidence="ECO:0000305"
FT CONFLICT 242..243
FT /note="AQ -> SP (in Ref. 3; AAB01978)"
FT /evidence="ECO:0000305"
FT CONFLICT 246..248
FT /note="SQA -> GQV (in Ref. 3; AAB01978)"
FT /evidence="ECO:0000305"
FT CONFLICT 385..386
FT /note="DA -> EP (in Ref. 2; AAS18308)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 418 AA; 46760 MW; 53C377C6691F4A90 CRC64;
MGQPGNRSVF LLAPNGSHAP DQDVPQERDE AWVVGMAIVM SLIVLAIVFG NVLVITAIAK
FERLQTVTNY FITSLACADL VMGLAVVPFG ASHILMKMWT FGSFWCEFWI SIDVLCVTAS
IETLCVIAVD RYLAITSPFK YQCLLTKNKA RVVILMVWVV SGLISFLPIK MHWYQATHRE
ALNCYAEEAC CDFFTNQPYA IASSIVSFYL PLVVMVFVYS RVFQVARRQL QKIDKSEGRF
HAQNLSQAEQ DGRSGPGHRR SSKFCLKEHK ALKTLGIIMG TFTLCWLPFF IVNIVHGIHD
NLIPKEVYIL LNWVGYVNSA FNPLIYCRSP DFRMAFQELL CLHRSSLKAY GNGCSSNSNG
RTDYTGEQSG CYLGEEKDSE RLCEDAPGPE GCAHRQGTVP DDSTDSQGRN CSTNDSML
