ADRB3_HUMAN
ID ADRB3_HUMAN Reviewed; 408 AA.
AC P13945; Q4JFT4;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 3.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Beta-3 adrenergic receptor;
DE AltName: Full=Beta-3 adrenoreceptor;
DE Short=Beta-3 adrenoceptor;
GN Name=ADRB3; Synonyms=ADRB3R, B3AR;
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 [GENOMIC DNA].
RX PubMed=2570461; DOI=10.1126/science.2570461;
RA Emorine L.J., Marullo S., Briend-Sutren M.-M., Patey G., Tate K.,
RA Delavier-Klutchko C., Strosberg A.D.;
RT "Molecular characterization of the human beta 3-adrenergic receptor.";
RL Science 245:1118-1121(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND SEQUENCE REVISION.
RX PubMed=8389293; DOI=10.1111/j.1432-1033.1993.tb17861.x;
RA van Spronsen A., Nahmias C., Krief S., Briend-Sutren M.-M., Strosberg A.D.,
RA Emorine L.J.;
RT "The promoter and intron/exon structure of the human and mouse beta 3-
RT adrenergic-receptor genes.";
RL Eur. J. Biochem. 213:1117-1124(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8389717; DOI=10.1016/0014-5793(93)81377-c;
RA Lelias J.M., Kaghad M., Rodriguez M., Chalon P., Bonnin J., Dupre I.,
RA Delpech B., Bensaid M., Lefur G., Ferrara P., Caput D.;
RT "Molecular cloning of a human beta 3-adrenergic receptor cDNA.";
RL FEBS Lett. 324:127-130(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RA Kopatz S.A., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-64 AND CYS-353.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 392-408.
RX PubMed=1336117;
RA Granneman J.G., Lahners K.N., Rao D.D.;
RT "Rodent and human beta 3-adrenergic receptor genes contain an intron within
RT the protein-coding block.";
RL Mol. Pharmacol. 42:964-970(1992).
RN [8]
RP INTERACTION WITH ARRDC3.
RX PubMed=21982743; DOI=10.1016/j.cmet.2011.08.011;
RA Patwari P., Emilsson V., Schadt E.E., Chutkow W.A., Lee S., Marsili A.,
RA Zhang Y., Dobrin R., Cohen D.E., Larsen P.R., Zavacki A.M., Fong L.G.,
RA Young S.G., Lee R.T.;
RT "The arrestin domain-containing 3 protein regulates body mass and energy
RT expenditure.";
RL Cell Metab. 14:671-683(2011).
RN [9]
RP VARIANT ARG-64.
RX PubMed=7609752; DOI=10.1056/nejm199508103330605;
RA Clement K., Vaisse C., Manning B.S.J., Basdevant A., Guy-Grand B., Ruiz J.,
RA Silver K.D., Shuldiner A.R., Froguel P., Strosberg A.D.;
RT "Genetic variation in the beta 3-adrenergic receptor and an increased
RT capacity to gain weight in patients with morbid obesity.";
RL N. Engl. J. Med. 333:352-354(1995).
RN [10]
RP VARIANT ARG-64.
RX PubMed=8721782; DOI=10.1007/bf00418352;
RA Fujisawa T., Ikegami H., Yamato E., Takekawa K., Nakagawa Y., Hamada Y.,
RA Oga T., Ueda H., Shintani M., Fukuda M., Ogihara T.;
RT "Association of Trp64Arg mutation of the beta3-adrenergic-receptor with
RT NIDDM and body weight gain.";
RL Diabetologia 39:349-352(1996).
RN [11]
RP VARIANT ARG-64.
RX PubMed=8641219; DOI=10.1210/endo.137.6.8641219;
RA Candelore M.R., Deng L., Tota L.M., Kelly L.J., Cascieri M.A.,
RA Strader C.D.;
RT "Pharmacological characterization of a recently described human beta 3-
RT adrenergic receptor mutant.";
RL Endocrinology 137:2638-2641(1996).
RN [12]
RP VARIANTS ARG-64 AND MET-265.
RX PubMed=10391210; DOI=10.1038/10297;
RA Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A.,
RA Cooper R., Lipshutz R., Chakravarti A.;
RT "Patterns of single-nucleotide polymorphisms in candidate genes for blood-
RT pressure homeostasis.";
RL Nat. Genet. 22:239-247(1999).
CC -!- FUNCTION: Beta-adrenergic receptors mediate the catecholamine-induced
CC activation of adenylate cyclase through the action of G proteins. Beta-
CC 3 is involved in the regulation of lipolysis and thermogenesis.
CC -!- SUBUNIT: Interacts with ARRDC3. {ECO:0000269|PubMed:21982743}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed mainly in adipose tissues.
CC -!- POLYMORPHISM: The variant Arg-64 seems to be associated with weight
CC gain (obesity) and is also associated with susceptibility to non-
CC insulin-dependent diabetes mellitus (NIDDM).
CC {ECO:0000269|PubMed:8721782, ECO:0000305|PubMed:7609752}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC Adrenergic receptor subfamily. ADRB3 sub-subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/adrb3/";
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DR EMBL; M29932; AAA35550.1; ALT_TERM; Genomic_DNA.
DR EMBL; X72861; CAA51383.1; -; Genomic_DNA.
DR EMBL; X70811; CAA50141.1; -; mRNA.
DR EMBL; X70812; CAA50142.1; ALT_SEQ; Genomic_DNA.
DR EMBL; X70812; CAA50143.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AY487247; AAR37414.1; -; mRNA.
DR EMBL; DQ104441; AAY88743.1; -; Genomic_DNA.
DR EMBL; BC075017; AAH75017.1; -; mRNA.
DR EMBL; S53291; AAB24837.1; -; mRNA.
DR CCDS; CCDS6099.1; -.
DR PIR; I57941; I57941.
DR PIR; S33751; QRHUBE.
DR RefSeq; NP_000016.1; NM_000025.2.
DR AlphaFoldDB; P13945; -.
DR SMR; P13945; -.
DR BioGRID; 106664; 2.
DR DIP; DIP-61451N; -.
DR IntAct; P13945; 6.
DR STRING; 9606.ENSP00000343782; -.
DR BindingDB; P13945; -.
DR ChEMBL; CHEMBL246; -.
DR DrugBank; DB00866; Alprenolol.
DR DrugBank; DB05395; Amibegron.
DR DrugBank; DB01118; Amiodarone.
DR DrugBank; DB00182; Amphetamine.
DR DrugBank; DB01102; Arbutamine.
DR DrugBank; DB00217; Bethanidine.
DR DrugBank; DB08807; Bopindolol.
DR DrugBank; DB06726; Bufuralol.
DR DrugBank; DB08808; Bupranolol.
DR DrugBank; DB04846; Celiprolol.
DR DrugBank; DB01407; Clenbuterol.
DR DrugBank; DB00785; Cryptenamine.
DR DrugBank; DB11273; Dihydroergocornine.
DR DrugBank; DB13345; Dihydroergocristine.
DR DrugBank; DB00320; Dihydroergotamine.
DR DrugBank; DB11278; DL-Methylephedrine.
DR DrugBank; DB06262; Droxidopa.
DR DrugBank; DB01363; Ephedra sinica root.
DR DrugBank; DB01049; Ergoloid mesylate.
DR DrugBank; DB01288; Fenoterol.
DR DrugBank; DB00983; Formoterol.
DR DrugBank; DB01064; Isoprenaline.
DR DrugBank; DB01365; Mephentermine.
DR DrugBank; DB08893; Mirabegron.
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; DB00960; Pindolol.
DR DrugBank; DB00571; Propranolol.
DR DrugBank; DB11124; Racepinephrine.
DR DrugBank; DB01001; Salbutamol.
DR DrugBank; DB00938; Salmeterol.
DR DrugBank; DB06190; Solabegron.
DR DrugBank; DB00871; Terbutaline.
DR DrugBank; DB00726; Trimipramine.
DR DrugBank; DB14895; Vibegron.
DR DrugCentral; P13945; -.
DR GuidetoPHARMACOLOGY; 30; -.
DR GlyGen; P13945; 2 sites.
DR PhosphoSitePlus; P13945; -.
DR SwissPalm; P13945; -.
DR BioMuta; ADRB3; -.
DR DMDM; 461604; -.
DR PaxDb; P13945; -.
DR PeptideAtlas; P13945; -.
DR PRIDE; P13945; -.
DR Antibodypedia; 10846; 421 antibodies from 38 providers.
DR DNASU; 155; -.
DR Ensembl; ENST00000345060.5; ENSP00000343782.3; ENSG00000188778.6.
DR GeneID; 155; -.
DR KEGG; hsa:155; -.
DR MANE-Select; ENST00000345060.5; ENSP00000343782.3; NM_000025.3; NP_000016.1.
DR UCSC; uc003xkr.3; human.
DR CTD; 155; -.
DR DisGeNET; 155; -.
DR GeneCards; ADRB3; -.
DR HGNC; HGNC:288; ADRB3.
DR HPA; ENSG00000188778; Tissue enhanced (brain, ovary).
DR MalaCards; ADRB3; -.
DR MIM; 109691; gene.
DR neXtProt; NX_P13945; -.
DR OpenTargets; ENSG00000188778; -.
DR PharmGKB; PA24598; -.
DR VEuPathDB; HostDB:ENSG00000188778; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000158663; -.
DR HOGENOM; CLU_009579_11_0_1; -.
DR InParanoid; P13945; -.
DR OMA; WPHENSS; -.
DR OrthoDB; 614199at2759; -.
DR PhylomeDB; P13945; -.
DR TreeFam; TF316350; -.
DR PathwayCommons; P13945; -.
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; P13945; -.
DR SIGNOR; P13945; -.
DR BioGRID-ORCS; 155; 16 hits in 1083 CRISPR screens.
DR GeneWiki; Beta-3_adrenergic_receptor; -.
DR GenomeRNAi; 155; -.
DR Pharos; P13945; Tclin.
DR PRO; PR:P13945; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P13945; protein.
DR Bgee; ENSG00000188778; Expressed in right ovary and 56 other tissues.
DR ExpressionAtlas; P13945; baseline and differential.
DR Genevisible; P13945; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043235; C:receptor complex; IDA:HGNC-UCL.
DR GO; GO:0031699; F:beta-3 adrenergic receptor binding; IEA:Ensembl.
DR GO; GO:0004939; F:beta-adrenergic receptor activity; IDA:HGNC-UCL.
DR GO; GO:0015052; F:beta3-adrenergic receptor activity; IMP:HGNC-UCL.
DR GO; GO:0051379; F:epinephrine binding; IBA:GO_Central.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0051380; F:norepinephrine binding; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:HGNC-UCL.
DR GO; GO:0007190; P:activation of adenylate cyclase activity; IDA:HGNC-UCL.
DR GO; GO:0071880; P:adenylate cyclase-activating adrenergic receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0050873; P:brown fat cell differentiation; IEA:Ensembl.
DR GO; GO:0005975; P:carbohydrate metabolic process; TAS:ProtInc.
DR GO; GO:0002024; P:diet induced thermogenesis; IEA:Ensembl.
DR GO; GO:0042755; P:eating behavior; IEA:Ensembl.
DR GO; GO:0006112; P:energy reserve metabolic process; TAS:ProtInc.
DR GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; TAS:ProtInc.
DR GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:ProtInc.
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:0043410; P:positive regulation of MAPK cascade; IDA:HGNC-UCL.
DR GO; GO:0046677; P:response to antibiotic; IEA:Ensembl.
DR GO; GO:0009409; P:response to cold; IEA:Ensembl.
DR InterPro; IPR002233; ADR_fam.
DR InterPro; IPR000681; ADRB3_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR01103; ADRENERGICR.
DR PRINTS; PR00563; ADRENRGCB3AR.
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 Cell membrane; Diabetes mellitus; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane; Obesity;
KW Palmitate; Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..408
FT /note="Beta-3 adrenergic receptor"
FT /id="PRO_0000069143"
FT TOPO_DOM 1..36
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 37..63
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 64..72
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 73..91
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 92..111
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 112..133
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250"
FT TOPO_DOM 134..155
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 156..178
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250"
FT TOPO_DOM 179..203
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 204..225
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250"
FT TOPO_DOM 226..292
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 293..314
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250"
FT TOPO_DOM 315..326
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 327..347
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250"
FT TOPO_DOM 348..408
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT LIPID 361
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 8
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 26
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 110..196
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 189..195
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VARIANT 64
FT /note="W -> R (in dbSNP:rs4994)"
FT /evidence="ECO:0000269|PubMed:10391210,
FT ECO:0000269|PubMed:7609752, ECO:0000269|PubMed:8641219,
FT ECO:0000269|PubMed:8721782, ECO:0000269|Ref.5"
FT /id="VAR_003456"
FT VARIANT 249
FT /note="E -> K (in dbSNP:rs28364012)"
FT /id="VAR_029205"
FT VARIANT 265
FT /note="T -> M (in dbSNP:rs4995)"
FT /evidence="ECO:0000269|PubMed:10391210"
FT /id="VAR_014166"
FT VARIANT 353
FT /note="R -> C (in dbSNP:rs36031925)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_025102"
SQ SEQUENCE 408 AA; 43519 MW; E98BD6C130DD977B CRC64;
MAPWPHENSS LAPWPDLPTL APNTANTSGL PGVPWEAALA GALLALAVLA TVGGNLLVIV
AIAWTPRLQT MTNVFVTSLA AADLVMGLLV VPPAATLALT GHWPLGATGC ELWTSVDVLC
VTASIETLCA LAVDRYLAVT NPLRYGALVT KRCARTAVVL VWVVSAAVSF APIMSQWWRV
GADAEAQRCH SNPRCCAFAS NMPYVLLSSS VSFYLPLLVM LFVYARVFVV ATRQLRLLRG
ELGRFPPEES PPAPSRSLAP APVGTCAPPE GVPACGRRPA RLLPLREHRA LCTLGLIMGT
FTLCWLPFFL ANVLRALGGP SLVPGPAFLA LNWLGYANSA FNPLIYCRSP DFRSAFRRLL
CRCGRRLPPE PCAAARPALF PSGVPAARSS PAQPRLCQRL DGASWGVS
