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Protein

Beta-3 adrenergic receptor

Gene

ADRB3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. Beta-3 is involved in the regulation of lipolysis and thermogenesis.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei117 – 1171Agonist or antagonistBy similarity
Binding sitei122 – 1221Agonist or antagonistBy similarity

GO - Molecular functioni

  • beta3-adrenergic receptor activity Source: HGNC
  • beta-adrenergic receptor activity Source: HGNC
  • epinephrine binding Source: GO_Central
  • norepinephrine binding Source: Ensembl
  • protein homodimerization activity Source: HGNC

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_16927. Adrenoceptors.
REACT_19327. G alpha (s) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Beta-3 adrenergic receptor
Alternative name(s):
Beta-3 adrenoreceptor
Short name:
Beta-3 adrenoceptor
Gene namesi
Name:ADRB3
Synonyms:ADRB3R, B3AR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:288. ADRB3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3636ExtracellularBy similarityAdd
BLAST
Transmembranei37 – 6327Helical; Name=1By similarityAdd
BLAST
Topological domaini64 – 729CytoplasmicBy similarity
Transmembranei73 – 9119Helical; Name=2By similarityAdd
BLAST
Topological domaini92 – 11120ExtracellularBy similarityAdd
BLAST
Transmembranei112 – 13322Helical; Name=3By similarityAdd
BLAST
Topological domaini134 – 15522CytoplasmicBy similarityAdd
BLAST
Transmembranei156 – 17823Helical; Name=4By similarityAdd
BLAST
Topological domaini179 – 20325ExtracellularBy similarityAdd
BLAST
Transmembranei204 – 22522Helical; Name=5By similarityAdd
BLAST
Topological domaini226 – 29267CytoplasmicBy similarityAdd
BLAST
Transmembranei293 – 31422Helical; Name=6By similarityAdd
BLAST
Topological domaini315 – 32612ExtracellularBy similarityAdd
BLAST
Transmembranei327 – 34721Helical; Name=7By similarityAdd
BLAST
Topological domaini348 – 40861CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  • integral component of plasma membrane Source: ProtInc
  • nucleus Source: Ensembl
  • plasma membrane Source: Reactome
  • receptor complex Source: HGNC
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Keywords - Diseasei

Diabetes mellitus, Obesity

Organism-specific databases

PharmGKBiPA24598.

Chemistry

DrugBankiDB00321. Amitriptyline.
DB00182. Amphetamine.
DB01102. Arbutamine.
DB00217. Bethanidine.
DB08807. Bopindolol.
DB08808. Bupranolol.
DB01407. Clenbuterol.
DB06262. Droxidopa.
DB01363. Ephedra.
DB00668. Epinephrine.
DB01288. Fenoterol.
DB01064. Isoprenaline.
DB01365. Mephentermine.
DB08893. Mirabegron.
DB00368. Norepinephrine.
DB00540. Nortriptyline.
DB00334. Olanzapine.
DB00571. Propranolol.
DB00726. Trimipramine.

Polymorphism and mutation databases

BioMutaiADRB3.
DMDMi461604.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 408408Beta-3 adrenergic receptorPRO_0000069143Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi8 – 81N-linked (GlcNAc...)Sequence Analysis
Glycosylationi26 – 261N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi110 ↔ 196PROSITE-ProRule annotation
Disulfide bondi189 ↔ 195PROSITE-ProRule annotation
Lipidationi361 – 3611S-palmitoyl cysteineBy similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiP13945.
PRIDEiP13945.

Expressioni

Tissue specificityi

Expressed mainly in adipose tissues.

Gene expression databases

BgeeiP13945.
CleanExiHS_ADRB3.
ExpressionAtlasiP13945. baseline and differential.
GenevisibleiP13945. HS.

Interactioni

Protein-protein interaction databases

BioGridi106664. 2 interactions.
IntActiP13945. 3 interactions.
STRINGi9606.ENSP00000343782.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2CDWmodel-A1-408[»]
ProteinModelPortaliP13945.
SMRiP13945. Positions 35-361.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni198 – 21215Agonist and antagonist bindingBy similarityAdd
BLAST
Regioni305 – 3128Agonist and antagonist bindingBy similarity
Regioni332 – 3365Agonist and antagonist bindingBy similarity

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB3 sub-subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG262978.
GeneTreeiENSGT00760000118774.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP13945.
KOiK04143.
OMAiQPRLCQR.
OrthoDBiEOG7BS4BS.
PhylomeDBiP13945.
TreeFamiTF316350.

Family and domain databases

InterProiIPR002233. ADR_fam.
IPR000681. ADRB3_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01103. ADRENERGICR.
PR00563. ADRENRGCB3AR.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P13945-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPWPHENSS LAPWPDLPTL APNTANTSGL PGVPWEAALA GALLALAVLA
60 70 80 90 100
TVGGNLLVIV AIAWTPRLQT MTNVFVTSLA AADLVMGLLV VPPAATLALT
110 120 130 140 150
GHWPLGATGC ELWTSVDVLC VTASIETLCA LAVDRYLAVT NPLRYGALVT
160 170 180 190 200
KRCARTAVVL VWVVSAAVSF APIMSQWWRV GADAEAQRCH SNPRCCAFAS
210 220 230 240 250
NMPYVLLSSS VSFYLPLLVM LFVYARVFVV ATRQLRLLRG ELGRFPPEES
260 270 280 290 300
PPAPSRSLAP APVGTCAPPE GVPACGRRPA RLLPLREHRA LCTLGLIMGT
310 320 330 340 350
FTLCWLPFFL ANVLRALGGP SLVPGPAFLA LNWLGYANSA FNPLIYCRSP
360 370 380 390 400
DFRSAFRRLL CRCGRRLPPE PCAAARPALF PSGVPAARSS PAQPRLCQRL

DGASWGVS
Length:408
Mass (Da):43,519
Last modified:February 1, 1994 - v3
Checksum:iE98BD6C130DD977B
GO

Polymorphismi

The variant Arg-64 seems to be associated with weight gain (obesity) and is also associated with susceptibility to non-insulin-dependent diabetes mellitus (NIDDM).

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti64 – 641W → R.5 Publications
Corresponds to variant rs4994 [ dbSNP | Ensembl ].
VAR_003456
Natural varianti249 – 2491E → K.
Corresponds to variant rs28364012 [ dbSNP | Ensembl ].
VAR_029205
Natural varianti265 – 2651T → M.1 Publication
Corresponds to variant rs4995 [ dbSNP | Ensembl ].
VAR_014166
Natural varianti353 – 3531R → C.1 Publication
Corresponds to variant rs36031925 [ dbSNP | Ensembl ].
VAR_025102

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M29932 Genomic DNA. Translation: AAA35550.1. Different termination.
X72861 Genomic DNA. Translation: CAA51383.1.
X70811 mRNA. Translation: CAA50141.1.
X70812 Genomic DNA. Translation: CAA50142.1. Sequence problems.
X70812 Genomic DNA. Translation: CAA50143.1. Sequence problems.
AY487247 mRNA. Translation: AAR37414.1.
DQ104441 Genomic DNA. Translation: AAY88743.1.
BC075017 mRNA. Translation: AAH75017.1.
S53291 mRNA. Translation: AAB24837.1.
CCDSiCCDS6099.1.
PIRiI57941.
S33751. QRHUBE.
RefSeqiNP_000016.1. NM_000025.2.
UniGeneiHs.2549.

Genome annotation databases

EnsembliENST00000345060; ENSP00000343782; ENSG00000188778.
ENST00000614635; ENSP00000480325; ENSG00000188778.
GeneIDi155.
KEGGihsa:155.
UCSCiuc003xkr.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M29932 Genomic DNA. Translation: AAA35550.1. Different termination.
X72861 Genomic DNA. Translation: CAA51383.1.
X70811 mRNA. Translation: CAA50141.1.
X70812 Genomic DNA. Translation: CAA50142.1. Sequence problems.
X70812 Genomic DNA. Translation: CAA50143.1. Sequence problems.
AY487247 mRNA. Translation: AAR37414.1.
DQ104441 Genomic DNA. Translation: AAY88743.1.
BC075017 mRNA. Translation: AAH75017.1.
S53291 mRNA. Translation: AAB24837.1.
CCDSiCCDS6099.1.
PIRiI57941.
S33751. QRHUBE.
RefSeqiNP_000016.1. NM_000025.2.
UniGeneiHs.2549.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2CDWmodel-A1-408[»]
ProteinModelPortaliP13945.
SMRiP13945. Positions 35-361.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106664. 2 interactions.
IntActiP13945. 3 interactions.
STRINGi9606.ENSP00000343782.

Chemistry

BindingDBiP13945.
ChEMBLiCHEMBL2097169.
DrugBankiDB00321. Amitriptyline.
DB00182. Amphetamine.
DB01102. Arbutamine.
DB00217. Bethanidine.
DB08807. Bopindolol.
DB08808. Bupranolol.
DB01407. Clenbuterol.
DB06262. Droxidopa.
DB01363. Ephedra.
DB00668. Epinephrine.
DB01288. Fenoterol.
DB01064. Isoprenaline.
DB01365. Mephentermine.
DB08893. Mirabegron.
DB00368. Norepinephrine.
DB00540. Nortriptyline.
DB00334. Olanzapine.
DB00571. Propranolol.
DB00726. Trimipramine.
GuidetoPHARMACOLOGYi30.

Protein family/group databases

GPCRDBiSearch...

Polymorphism and mutation databases

BioMutaiADRB3.
DMDMi461604.

Proteomic databases

PaxDbiP13945.
PRIDEiP13945.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000345060; ENSP00000343782; ENSG00000188778.
ENST00000614635; ENSP00000480325; ENSG00000188778.
GeneIDi155.
KEGGihsa:155.
UCSCiuc003xkr.2. human.

Organism-specific databases

CTDi155.
GeneCardsiGC08M037822.
HGNCiHGNC:288. ADRB3.
MIMi109691. gene.
neXtProtiNX_P13945.
PharmGKBiPA24598.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG262978.
GeneTreeiENSGT00760000118774.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP13945.
KOiK04143.
OMAiQPRLCQR.
OrthoDBiEOG7BS4BS.
PhylomeDBiP13945.
TreeFamiTF316350.

Enzyme and pathway databases

ReactomeiREACT_16927. Adrenoceptors.
REACT_19327. G alpha (s) signalling events.

Miscellaneous databases

GeneWikiiBeta-3_adrenergic_receptor.
GenomeRNAii155.
NextBioi617.
PROiP13945.
SOURCEiSearch...

Gene expression databases

BgeeiP13945.
CleanExiHS_ADRB3.
ExpressionAtlasiP13945. baseline and differential.
GenevisibleiP13945. HS.

Family and domain databases

InterProiIPR002233. ADR_fam.
IPR000681. ADRB3_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01103. ADRENERGICR.
PR00563. ADRENRGCB3AR.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "The promoter and intron/exon structure of the human and mouse beta 3-adrenergic-receptor genes."
    van Spronsen A., Nahmias C., Krief S., Briend-Sutren M.-M., Strosberg A.D., Emorine L.J.
    Eur. J. Biochem. 213:1117-1124(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], SEQUENCE REVISION.
  3. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. "cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
    Kopatz S.A., Aronstam R.S., Sharma S.V.
    Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Placenta.
  5. SeattleSNPs variation discovery resource
    Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-64 AND CYS-353.
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  7. "Rodent and human beta 3-adrenergic receptor genes contain an intron within the protein-coding block."
    Granneman J.G., Lahners K.N., Rao D.D.
    Mol. Pharmacol. 42:964-970(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 392-408.
  8. "Genetic variation in the beta 3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity."
    Clement K., Vaisse C., Manning B.S.J., Basdevant A., Guy-Grand B., Ruiz J., Silver K.D., Shuldiner A.R., Froguel P., Strosberg A.D.
    N. Engl. J. Med. 333:352-354(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT ARG-64.
  9. "Association of Trp64Arg mutation of the beta3-adrenergic-receptor with NIDDM and body weight gain."
    Fujisawa T., Ikegami H., Yamato E., Takekawa K., Nakagawa Y., Hamada Y., Oga T., Ueda H., Shintani M., Fukuda M., Ogihara T.
    Diabetologia 39:349-352(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT ARG-64.
  10. "Pharmacological characterization of a recently described human beta 3-adrenergic receptor mutant."
    Candelore M.R., Deng L., Tota L.M., Kelly L.J., Cascieri M.A., Strader C.D.
    Endocrinology 137:2638-2641(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT ARG-64.
  11. "Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis."
    Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A., Cooper R., Lipshutz R., Chakravarti A.
    Nat. Genet. 22:239-247(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS ARG-64 AND MET-265.

Entry informationi

Entry nameiADRB3_HUMAN
AccessioniPrimary (citable) accession number: P13945
Secondary accession number(s): Q4JFT4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: February 1, 1994
Last modified: June 24, 2015
This is version 167 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.