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P13945

- ADRB3_HUMAN

UniProt

P13945 - ADRB3_HUMAN

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Protein

Beta-3 adrenergic receptor

Gene

ADRB3

Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. beta3-adrenergic receptor activity Source: HGNC
  2. beta-adrenergic receptor activity Source: HGNC
  3. epinephrine binding Source: Ensembl
  4. norepinephrine binding Source: Ensembl
  5. protein homodimerization activity Source: HGNC

GO - Biological processi

  1. activation of adenylate cyclase activity Source: HGNC
  2. adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: Ensembl
  3. adenylate cyclase-modulating G-protein coupled receptor signaling pathway Source: ProtInc
  4. adrenergic receptor signaling pathway Source: GOC
  5. aging Source: Ensembl
  6. brown fat cell differentiation Source: Ensembl
  7. carbohydrate metabolic process Source: ProtInc
  8. diet induced thermogenesis Source: Ensembl
  9. eating behavior Source: Ensembl
  10. energy reserve metabolic process Source: ProtInc
  11. generation of precursor metabolites and energy Source: ProtInc
  12. G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Source: ProtInc
  13. heat generation Source: Ensembl
  14. negative regulation of multicellular organism growth Source: Ensembl
  15. positive regulation of MAPK cascade Source: HGNC
  16. response to antibiotic Source: Ensembl
  17. response to cold Source: Ensembl
  18. vasodilation by norepinephrine-epinephrine involved in regulation of systemic arterial blood pressure Source: Ensembl
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: Chromosome 8

Organism-specific databases

HGNCiHGNC:288. ADRB3.

Subcellular locationi

GO - Cellular componenti

  1. integral component of plasma membrane Source: ProtInc
  2. nucleus Source: Ensembl
  3. plasma membrane Source: Reactome
  4. receptor complex Source: HGNC
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Keywords - Diseasei

Diabetes mellitus, Obesity

Organism-specific databases

PharmGKBiPA24598.

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.
GenevestigatoriP13945.

Interactioni

Protein-protein interaction databases

BioGridi106664. 1 interaction.
STRINGi9606.ENSP00000343782.

Structurei

3D structure databases

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

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3636ExtracellularBy similarityAdd
BLAST
Topological domaini64 – 729CytoplasmicBy similarity
Topological domaini92 – 11120ExtracellularBy similarityAdd
BLAST
Topological domaini134 – 15522CytoplasmicBy similarityAdd
BLAST
Topological domaini179 – 20325ExtracellularBy similarityAdd
BLAST
Topological domaini226 – 29267CytoplasmicBy similarityAdd
BLAST
Topological domaini315 – 32612ExtracellularBy similarityAdd
BLAST
Topological domaini348 – 40861CytoplasmicBy similarityAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei37 – 6327Helical; Name=1By similarityAdd
BLAST
Transmembranei73 – 9119Helical; Name=2By similarityAdd
BLAST
Transmembranei112 – 13322Helical; Name=3By similarityAdd
BLAST
Transmembranei156 – 17823Helical; Name=4By similarityAdd
BLAST
Transmembranei204 – 22522Helical; Name=5By similarityAdd
BLAST
Transmembranei293 – 31422Helical; Name=6By similarityAdd
BLAST
Transmembranei327 – 34721Helical; Name=7By similarityAdd
BLAST

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.
OMAiRRLLCRC.
OrthoDBiEOG7BS4BS.
PhylomeDBiP13945.
TreeFamiTF316350.

Family and domain databases

Gene3Di1.20.1070.10. 1 hit.
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 [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:
EMBL
GenBank
DDBJ
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.

Polymorphism databases

DMDMi461604.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS6099.1.
PIRi I57941.
S33751. QRHUBE.
RefSeqi NP_000016.1. NM_000025.2.
UniGenei Hs.2549.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2CDW model - A 1-408 [» ]
ProteinModelPortali P13945.
SMRi P13945. Positions 35-361.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 106664. 1 interaction.
STRINGi 9606.ENSP00000343782.

Chemistry

BindingDBi P13945.
ChEMBLi CHEMBL2097169.
DrugBanki DB00321. 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.
GuidetoPHARMACOLOGYi 30.

Protein family/group databases

GPCRDBi Search...

Polymorphism databases

DMDMi 461604.

Proteomic databases

PaxDbi P13945.
PRIDEi P13945.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000345060 ; ENSP00000343782 ; ENSG00000188778 .
ENST00000614635 ; ENSP00000480325 ; ENSG00000188778 .
GeneIDi 155.
KEGGi hsa:155.
UCSCi uc003xkr.2. human.

Organism-specific databases

CTDi 155.
GeneCardsi GC08M037822.
HGNCi HGNC:288. ADRB3.
MIMi 109691. gene.
neXtProti NX_P13945.
PharmGKBi PA24598.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG262978.
GeneTreei ENSGT00760000118774.
HOGENOMi HOG000239242.
HOVERGENi HBG106962.
InParanoidi P13945.
KOi K04143.
OMAi RRLLCRC.
OrthoDBi EOG7BS4BS.
PhylomeDBi P13945.
TreeFami TF316350.

Enzyme and pathway databases

Reactomei REACT_16927. Adrenoceptors.
REACT_19327. G alpha (s) signalling events.

Miscellaneous databases

GeneWikii Beta-3_adrenergic_receptor.
GenomeRNAii 155.
NextBioi 617.
PROi P13945.
SOURCEi Search...

Gene expression databases

Bgeei P13945.
CleanExi HS_ADRB3.
ExpressionAtlasi P13945. baseline and differential.
Genevestigatori P13945.

Family and domain databases

Gene3Di 1.20.1070.10. 1 hit.
InterProi IPR002233. ADR_fam.
IPR000681. ADRB3_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view ]
Pfami PF00001. 7tm_1. 1 hit.
[Graphical view ]
PRINTSi PR01103. ADRENERGICR.
PR00563. ADRENRGCB3AR.
PR00237. GPCRRHODOPSN.
PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: October 29, 2014
This is version 162 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