ADRB1_HUMAN
ID ADRB1_HUMAN Reviewed; 477 AA.
AC P08588; B0LPE2; Q5T5Y4; Q9UKG7; Q9UKG8;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 2.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Beta-1 adrenergic receptor {ECO:0000305};
DE AltName: Full=Beta-1 adrenoreceptor;
DE Short=Beta-1 adrenoceptor;
GN Name=ADRB1 {ECO:0000312|HGNC:HGNC:285}; Synonyms=ADRB1R, B1AR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=2825170; DOI=10.1073/pnas.84.22.7920;
RA Frielle T., Collins S., Daniel K.W., Caron M.G., Lefkowitz R.J.,
RA Kobilka B.K.;
RT "Cloning of the cDNA for the human beta 1-adrenergic receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:7920-7924(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLY-49 AND GLY-389.
RX PubMed=10477438;
RX DOI=10.1002/(sici)1098-1004(1999)14:3<271::aid-humu14>3.0.co;2-q;
RA Moore J.D., Mason D.A., Green S.A., Hsu J., Liggett S.B.;
RT "Racial differences in the frequencies of cardiac beta(1)-adrenergic
RT receptor polymorphisms: analysis of c145A>G and c1165G>C.";
RL Hum. Mutat. 14:271-271(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLY-49; GLY-389 AND
RP LEU-389.
RG SeattleSNPs variation discovery resource;
RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLY-389.
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP FUNCTION, INTERACTION WITH RAPGEF2, AND MUTAGENESIS OF SER-475 AND VAL-477.
RX PubMed=12391161; DOI=10.1128/mcb.22.22.7942-7952.2002;
RA Pak Y., Pham N., Rotin D.;
RT "Direct binding of the beta1 adrenergic receptor to the cyclic AMP-
RT dependent guanine nucleotide exchange factor CNrasGEF leads to Ras
RT activation.";
RL Mol. Cell. Biol. 22:7942-7952(2002).
RN [7]
RP INTERACTION WITH GOPC AND DLG4, MUTAGENESIS OF GLU-474; SER-475; LYS-476
RP AND VAL-477, AND SUBCELLULAR LOCATION.
RX PubMed=15358775; DOI=10.1074/jbc.m404876200;
RA He J., Bellini M., Xu J., Castleberry A.M., Hall R.A.;
RT "Interaction with cystic fibrosis transmembrane conductance regulator-
RT associated ligand (CAL) inhibits beta1-adrenergic receptor surface
RT expression.";
RL J. Biol. Chem. 279:50190-50196(2004).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=21540189; DOI=10.1074/jbc.m111.224071;
RA Cheng S.B., Quinn J.A., Graeber C.T., Filardo E.J.;
RT "Down-modulation of the G-protein-coupled estrogen receptor, GPER, from the
RT cell surface occurs via a trans-Golgi-proteasome pathway.";
RL J. Biol. Chem. 286:22441-22455(2011).
RN [9]
RP VARIANT GLY-389.
RX PubMed=10212248; DOI=10.1074/jbc.274.18.12670;
RA Mason D.A., Moore J.D., Green S.A., Liggett S.B.;
RT "A gain-of-function polymorphism in a G-protein coupling domain of the
RT human beta1-adrenergic receptor.";
RL J. Biol. Chem. 274:12670-12674(1999).
RN [10]
RP VARIANT GLY-49.
RX PubMed=11052857; DOI=10.1053/euhj.1999.1994;
RA Borjesson M., Magnusson Y., Hjalmarson A., Andersson B.;
RT "A novel polymorphism in the gene coding for the beta(1)-adrenergic
RT receptor associated with survival in patients with heart failure.";
RL Eur. Heart J. 21:1853-1858(2000).
RN [11]
RP VARIANT GLY-49, AND POLYMORPHISM.
RX PubMed=11854867; DOI=10.1086/339621;
RA Ranade K., Jorgenson E., Sheu W.H.-H., Pei D., Hsiung C.A., Chiang F.-T.,
RA Chen Y.-D.I., Pratt R., Olshen R.A., Curb D., Cox D.R., Botstein D.,
RA Risch N.;
RT "A polymorphism in the beta1 adrenergic receptor is associated with resting
RT heart rate.";
RL Am. J. Hum. Genet. 70:935-942(2002).
RN [12]
RP VARIANT VAL-187, CHARACTERIZATION OF VARIANT VAL-187, FUNCTION, AND
RP POLYMORPHISM.
RX PubMed=31473062; DOI=10.1016/j.neuron.2019.07.026;
RA Shi G., Xing L., Wu D., Bhattacharyya B.J., Jones C.R., McMahon T.,
RA Chong S.Y.C., Chen J.A., Coppola G., Geschwind D., Krystal A., Ptacek L.J.,
RA Fu Y.H.;
RT "A rare mutation of beta1-adrenergic receptor affects sleep/wake
RT behaviors.";
RL Neuron 0:0-0(2019).
CC -!- FUNCTION: Beta-adrenergic receptors mediate the catecholamine-induced
CC activation of adenylate cyclase through the action of G proteins. This
CC receptor binds epinephrine and norepinephrine with approximately equal
CC affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated
CC signaling. Involved in the regulation of sleep/wake behaviors
CC (PubMed:31473062). {ECO:0000269|PubMed:12391161,
CC ECO:0000269|PubMed:31473062}.
CC -!- SUBUNIT: Interacts (via C-terminus PDZ motif) with RAPGEF2; the
CC interaction is direct. Interacts with GOPC, MAGI3 and DLG4.
CC {ECO:0000269|PubMed:12391161, ECO:0000269|PubMed:15358775}.
CC -!- INTERACTION:
CC P08588; P30542: ADORA1; NbExp=5; IntAct=EBI-991009, EBI-2903663;
CC P08588; Q86UL8: MAGI2; NbExp=3; IntAct=EBI-991009, EBI-311035;
CC P08588; Q5TCQ9: MAGI3; NbExp=5; IntAct=EBI-991009, EBI-310506;
CC P08588; P31016: Dlg4; Xeno; NbExp=2; IntAct=EBI-991009, EBI-375655;
CC P08588; P14270: Pde4d; Xeno; NbExp=2; IntAct=EBI-991009, EBI-8333209;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P18090};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P18090}. Early
CC endosome. Note=Colocalizes with RAPGEF2 at the plasma membrane (By
CC similarity). Localized at the plasma membrane. Found in the Golgi upon
CC GOPC overexpression. {ECO:0000250}.
CC -!- DOMAIN: The PDZ domain-binding motif mediates competitive interactions
CC with GOPC, MAGI3 and DLG4 and plays a role in subcellular location of
CC the receptor.
CC -!- PTM: Homologous desensitization of the receptor is mediated by its
CC phosphorylation by beta-adrenergic receptor kinase.
CC -!- POLYMORPHISM: Genetic variations in ADRB1 are associated with inter-
CC individual variability in the resting heart rate. This quantitative
CC trait has been significantly correlated with cardiovascular morbidity
CC and mortality [MIM:607276]. {ECO:0000269|PubMed:11854867}.
CC -!- POLYMORPHISM: Genetic variations in ADRB1 are associated with the
CC familial natural short sleep 2 (FNSS2) phenotype, an autosomal dominant
CC trait [MIM:618591]. Individuals with this trait require less sleep in
CC any 24-hour period than is typical for their age group.
CC {ECO:0000269|PubMed:31473062}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC Adrenergic receptor subfamily. ADRB1 sub-subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/adrb1/";
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DR EMBL; J03019; AAA51667.1; -; mRNA.
DR EMBL; AF169006; AAD53696.1; -; Genomic_DNA.
DR EMBL; AF169007; AAD53697.1; -; Genomic_DNA.
DR EMBL; AY567837; AAS66983.1; -; Genomic_DNA.
DR EMBL; EU332832; ABY87521.1; -; Genomic_DNA.
DR EMBL; AL355543; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS7586.1; -.
DR PIR; A39911; QRHUB1.
DR RefSeq; NP_000675.1; NM_000684.2.
DR PDB; 2LSQ; NMR; -; A=197-221.
DR PDB; 7BTS; X-ray; 3.13 A; A=54-399.
DR PDB; 7BU6; X-ray; 2.70 A; A=54-399.
DR PDB; 7BU7; X-ray; 2.60 A; A=54-399.
DR PDB; 7BVQ; X-ray; 2.50 A; A/B=54-399.
DR PDBsum; 2LSQ; -.
DR PDBsum; 7BTS; -.
DR PDBsum; 7BU6; -.
DR PDBsum; 7BU7; -.
DR PDBsum; 7BVQ; -.
DR AlphaFoldDB; P08588; -.
DR SMR; P08588; -.
DR BioGRID; 106662; 10.
DR CORUM; P08588; -.
DR DIP; DIP-36294N; -.
DR IntAct; P08588; 14.
DR MINT; P08588; -.
DR STRING; 9606.ENSP00000358301; -.
DR BindingDB; P08588; -.
DR ChEMBL; CHEMBL213; -.
DR DrugBank; DB08558; 2-HYDROXYMETHYL-6-OCTYLSULFANYL-TETRAHYDRO-PYRAN-3,4,5-TRIOL.
DR DrugBank; DB08347; 4-{[(2S)-3-(tert-butylamino)-2-hydroxypropyl]oxy}-3H-indole-2-carbonitrile.
DR DrugBank; DB01193; Acebutolol.
DR DrugBank; DB00866; Alprenolol.
DR DrugBank; DB01118; Amiodarone.
DR DrugBank; DB00182; Amphetamine.
DR DrugBank; DB01102; Arbutamine.
DR DrugBank; DB01238; Aripiprazole.
DR DrugBank; DB09204; Arotinolol.
DR DrugBank; DB06216; Asenapine.
DR DrugBank; DB00335; Atenolol.
DR DrugBank; DB09013; Befunolol.
DR DrugBank; DB00195; Betaxolol.
DR DrugBank; DB00217; Bethanidine.
DR DrugBank; DB01295; Bevantolol.
DR DrugBank; DB00612; Bisoprolol.
DR DrugBank; DB08807; Bopindolol.
DR DrugBank; DB06726; Bufuralol.
DR DrugBank; DB08808; Bupranolol.
DR DrugBank; DB00248; Cabergoline.
DR DrugBank; DB00521; Carteolol.
DR DrugBank; DB01136; Carvedilol.
DR DrugBank; DB04846; Celiprolol.
DR DrugBank; DB01407; Clenbuterol.
DR DrugBank; DB00785; Cryptenamine.
DR DrugBank; DB01151; Desipramine.
DR DrugBank; DB11273; Dihydroergocornine.
DR DrugBank; DB13345; Dihydroergocristine.
DR DrugBank; DB11278; DL-Methylephedrine.
DR DrugBank; DB00841; Dobutamine.
DR DrugBank; DB04855; Dronedarone.
DR DrugBank; DB06262; Droxidopa.
DR DrugBank; DB01363; Ephedra sinica root.
DR DrugBank; DB01364; Ephedrine.
DR DrugBank; DB00668; Epinephrine.
DR DrugBank; DB01049; Ergoloid mesylate.
DR DrugBank; DB00187; Esmolol.
DR DrugBank; DB01288; Fenoterol.
DR DrugBank; DB00983; Formoterol.
DR DrugBank; DB00221; Isoetharine.
DR DrugBank; DB01064; Isoprenaline.
DR DrugBank; DB00598; Labetalol.
DR DrugBank; DB00555; Lamotrigine.
DR DrugBank; DB09351; Levobetaxolol.
DR DrugBank; DB01210; Levobunolol.
DR DrugBank; DB00408; Loxapine.
DR DrugBank; DB01365; Mephentermine.
DR DrugBank; DB01214; Metipranolol.
DR DrugBank; DB00264; Metoprolol.
DR DrugBank; DB08893; Mirabegron.
DR DrugBank; DB01203; Nadolol.
DR DrugBank; DB04861; Nebivolol.
DR DrugBank; DB00368; Norepinephrine.
DR DrugBank; DB00540; Nortriptyline.
DR DrugBank; DB00334; Olanzapine.
DR DrugBank; DB01580; Oxprenolol.
DR DrugBank; DB00715; Paroxetine.
DR DrugBank; DB01359; Penbutolol.
DR DrugBank; DB00397; Phenylpropanolamine.
DR DrugBank; DB00960; Pindolol.
DR DrugBank; DB01291; Pirbuterol.
DR DrugBank; DB01297; Practolol.
DR DrugBank; DB01182; Propafenone.
DR DrugBank; DB00571; Propranolol.
DR DrugBank; DB00852; Pseudoephedrine.
DR DrugBank; DB01917; Putrescine.
DR DrugBank; DB11124; Racepinephrine.
DR DrugBank; DB00243; Ranolazine.
DR DrugBank; DB01001; Salbutamol.
DR DrugBank; DB00938; Salmeterol.
DR DrugBank; DB00489; Sotalol.
DR DrugBank; DB03566; Spermidine.
DR DrugBank; DB00127; Spermine.
DR DrugBank; DB00871; Terbutaline.
DR DrugBank; DB00373; Timolol.
DR DrugBank; DB00726; Trimipramine.
DR DrugBank; DB09068; Vortioxetine.
DR DrugBank; DB13781; Xamoterol.
DR DrugCentral; P08588; -.
DR GuidetoPHARMACOLOGY; 28; -.
DR TCDB; 9.A.14.3.11; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; P08588; 1 site.
DR iPTMnet; P08588; -.
DR PhosphoSitePlus; P08588; -.
DR SwissPalm; P08588; -.
DR BioMuta; ADRB1; -.
DR DMDM; 48429211; -.
DR jPOST; P08588; -.
DR PaxDb; P08588; -.
DR PeptideAtlas; P08588; -.
DR PRIDE; P08588; -.
DR ABCD; P08588; 1 sequenced antibody.
DR Antibodypedia; 31906; 270 antibodies from 37 providers.
DR DNASU; 153; -.
DR Ensembl; ENST00000369295.4; ENSP00000358301.2; ENSG00000043591.6.
DR GeneID; 153; -.
DR KEGG; hsa:153; -.
DR UCSC; uc001lba.4; human.
DR CTD; 153; -.
DR DisGeNET; 153; -.
DR GeneCards; ADRB1; -.
DR HGNC; HGNC:285; ADRB1.
DR HPA; ENSG00000043591; Tissue enhanced (heart muscle, lung, placenta).
DR MalaCards; ADRB1; -.
DR MIM; 109630; gene.
DR MIM; 607276; phenotype.
DR neXtProt; NX_P08588; -.
DR PharmGKB; PA38; -.
DR VEuPathDB; HostDB:ENSG00000043591; -.
DR eggNOG; KOG3656; Eukaryota.
DR HOGENOM; CLU_009579_11_0_1; -.
DR InParanoid; P08588; -.
DR OrthoDB; 750855at2759; -.
DR PhylomeDB; P08588; -.
DR TreeFam; TF316350; -.
DR PathwayCommons; P08588; -.
DR Reactome; R-HSA-390696; Adrenoceptors.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; P08588; -.
DR SIGNOR; P08588; -.
DR BioGRID-ORCS; 153; 13 hits in 1072 CRISPR screens.
DR GeneWiki; Beta-1_adrenergic_receptor; -.
DR GenomeRNAi; 153; -.
DR Pharos; P08588; Tclin.
DR PRO; PR:P08588; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P08588; protein.
DR Bgee; ENSG00000043591; Expressed in heart right ventricle and 140 other tissues.
DR Genevisible; P08588; HS.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl.
DR GO; GO:0031694; F:alpha-2A adrenergic receptor binding; IPI:BHF-UCL.
DR GO; GO:0004939; F:beta-adrenergic receptor activity; TAS:ProtInc.
DR GO; GO:0004940; F:beta1-adrenergic receptor activity; IBA:GO_Central.
DR GO; GO:0099579; F:G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential; IEA:Ensembl.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0030165; F:PDZ domain binding; IPI:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:BHF-UCL.
DR GO; GO:0007190; P:activation of adenylate cyclase activity; TAS:ProtInc.
DR GO; GO:0071880; P:adenylate cyclase-activating adrenergic receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0050873; P:brown fat cell differentiation; IEA:Ensembl.
DR GO; GO:0002024; P:diet induced thermogenesis; IEA:Ensembl.
DR GO; GO:0042596; P:fear response; 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:0002025; P:norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure; IBA:GO_Central.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0001996; P:positive regulation of heart rate by epinephrine-norepinephrine; IBA:GO_Central.
DR GO; GO:0001997; P:positive regulation of the force of heart contraction by epinephrine-norepinephrine; IEA:Ensembl.
DR GO; GO:0045187; P:regulation of circadian sleep/wake cycle, sleep; IMP:UniProtKB.
DR GO; GO:0009409; P:response to cold; IEA:Ensembl.
DR InterPro; IPR002233; ADR_fam.
DR InterPro; IPR000507; ADRB1_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR01103; ADRENERGICR.
DR PRINTS; PR00561; ADRENRGCB1AR.
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 3D-structure; Cell membrane; Disulfide bond; Endosome;
KW G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane; Palmitate;
KW Phosphoprotein; Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..477
FT /note="Beta-1 adrenergic receptor"
FT /id="PRO_0000069118"
FT TOPO_DOM 1..55
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 56..84
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 85..93
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 94..120
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 121..132
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 133..154
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250"
FT TOPO_DOM 155..172
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 173..196
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250"
FT TOPO_DOM 197..222
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 223..248
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250"
FT TOPO_DOM 249..319
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 320..349
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250"
FT TOPO_DOM 350..354
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 355..377
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250"
FT TOPO_DOM 378..477
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 269..307
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 403..477
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 474..477
FT /note="PDZ-Binding"
FT COMPBIAS 270..294
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 312
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000255"
FT MOD_RES 412
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000255"
FT MOD_RES 428
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P18090"
FT LIPID 392
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 15
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
FT DISULFID 131..216
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 209..215
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VARIANT 26
FT /note="A -> V (in dbSNP:rs34844626)"
FT /id="VAR_055909"
FT VARIANT 29
FT /note="A -> T (in dbSNP:rs35720093)"
FT /id="VAR_055910"
FT VARIANT 31
FT /note="R -> Q (in dbSNP:rs35230616)"
FT /id="VAR_055911"
FT VARIANT 49
FT /note="S -> G (common variant associated with low mean
FT resting heart rate; associated with decreased mortality
FT risk in patients with congestive heart failure;
FT dbSNP:rs1801252)"
FT /evidence="ECO:0000269|PubMed:10477438,
FT ECO:0000269|PubMed:11052857, ECO:0000269|PubMed:11854867,
FT ECO:0000269|Ref.3"
FT /id="VAR_009879"
FT VARIANT 187
FT /note="A -> V (rare variant associated with short sleep;
FT results in decreased adenylate cyclase-activating
FT adrenergic receptor signaling; decreased protein stability;
FT dbSNP:rs776439595)"
FT /evidence="ECO:0000269|PubMed:31473062"
FT /id="VAR_082587"
FT VARIANT 389
FT /note="R -> G (reduced binding to G proteins;
FT dbSNP:rs1801253)"
FT /evidence="ECO:0000269|PubMed:10212248,
FT ECO:0000269|PubMed:10477438, ECO:0000269|PubMed:15164054,
FT ECO:0000269|Ref.3"
FT /id="VAR_009880"
FT VARIANT 389
FT /note="R -> L (in dbSNP:rs17875445)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_018742"
FT VARIANT 399
FT /note="R -> H (in dbSNP:rs36052953)"
FT /id="VAR_055912"
FT VARIANT 405
FT /note="H -> Y (in dbSNP:rs35705839)"
FT /id="VAR_055913"
FT MUTAGEN 474
FT /note="E->A,D: Loss of interaction with GOPC."
FT /evidence="ECO:0000269|PubMed:15358775"
FT MUTAGEN 474
FT /note="E->K: Loss of interaction with GOPC; when associated
FT with A-477."
FT /evidence="ECO:0000269|PubMed:15358775"
FT MUTAGEN 475
FT /note="S->A: Loss of interaction with GOPC. Loss of
FT interaction with RAPGEF2. Abolishes agonist-induced Ras
FT activation."
FT /evidence="ECO:0000269|PubMed:12391161,
FT ECO:0000269|PubMed:15358775"
FT MUTAGEN 475
FT /note="S->D: Loss of interaction with RAPGEF2."
FT /evidence="ECO:0000269|PubMed:12391161,
FT ECO:0000269|PubMed:15358775"
FT MUTAGEN 475
FT /note="S->T: Partial loss of interaction with GOPC."
FT /evidence="ECO:0000269|PubMed:12391161,
FT ECO:0000269|PubMed:15358775"
FT MUTAGEN 476
FT /note="K->A: Partial loss of interaction with GOPC."
FT /evidence="ECO:0000269|PubMed:15358775"
FT MUTAGEN 477
FT /note="V->A,F,L,I,M: Loss of interaction with GOPC."
FT /evidence="ECO:0000269|PubMed:12391161,
FT ECO:0000269|PubMed:15358775"
FT MUTAGEN 477
FT /note="V->A: Loss of interaction with RAPGEF2. Abolishes
FT agonist-induced Ras activation."
FT /evidence="ECO:0000269|PubMed:12391161,
FT ECO:0000269|PubMed:15358775"
FT HELIX 54..85
FT /evidence="ECO:0007829|PDB:7BVQ"
FT HELIX 87..89
FT /evidence="ECO:0007829|PDB:7BVQ"
FT HELIX 92..110
FT /evidence="ECO:0007829|PDB:7BVQ"
FT HELIX 112..121
FT /evidence="ECO:0007829|PDB:7BVQ"
FT HELIX 127..161
FT /evidence="ECO:0007829|PDB:7BVQ"
FT HELIX 163..169
FT /evidence="ECO:0007829|PDB:7BVQ"
FT HELIX 172..195
FT /evidence="ECO:0007829|PDB:7BVQ"
FT TURN 196..199
FT /evidence="ECO:0007829|PDB:7BVQ"
FT HELIX 204..210
FT /evidence="ECO:0007829|PDB:7BVQ"
FT HELIX 213..215
FT /evidence="ECO:0007829|PDB:2LSQ"
FT HELIX 222..232
FT /evidence="ECO:0007829|PDB:7BVQ"
FT HELIX 234..253
FT /evidence="ECO:0007829|PDB:7BVQ"
FT HELIX 316..349
FT /evidence="ECO:0007829|PDB:7BVQ"
FT HELIX 351..353
FT /evidence="ECO:0007829|PDB:7BVQ"
FT HELIX 356..377
FT /evidence="ECO:0007829|PDB:7BVQ"
FT HELIX 381..391
FT /evidence="ECO:0007829|PDB:7BVQ"
SQ SEQUENCE 477 AA; 51323 MW; 0950F2684E4721B8 CRC64;
MGAGVLVLGA SEPGNLSSAA PLPDGAATAA RLLVPASPPA SLLPPASESP EPLSQQWTAG
MGLLMALIVL LIVAGNVLVI VAIAKTPRLQ TLTNLFIMSL ASADLVMGLL VVPFGATIVV
WGRWEYGSFF CELWTSVDVL CVTASIETLC VIALDRYLAI TSPFRYQSLL TRARARGLVC
TVWAISALVS FLPILMHWWR AESDEARRCY NDPKCCDFVT NRAYAIASSV VSFYVPLCIM
AFVYLRVFRE AQKQVKKIDS CERRFLGGPA RPPSPSPSPV PAPAPPPGPP RPAAAAATAP
LANGRAGKRR PSRLVALREQ KALKTLGIIM GVFTLCWLPF FLANVVKAFH RELVPDRLFV
FFNWLGYANS AFNPIIYCRS PDFRKAFQRL LCCARRAARR RHATHGDRPR ASGCLARPGP
PPSPGAASDD DDDDVVGATP PARLLEPWAG CNGGAAADSD SSLDEPCRPG FASESKV
