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P13945 (ADRB3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Beta-3 adrenergic receptor
Alternative name(s):
Beta-3 adrenoreceptor
Short name=Beta-3 adrenoceptor
Gene names
Name:ADRB3
Synonyms:ADRB3R, B3AR
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length408 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Expressed mainly in adipose tissues.

Polymorphism

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

Sequence similarities

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 408408Beta-3 adrenergic receptor
PRO_0000069143

Regions

Topological domain1 – 3636Extracellular By similarity
Transmembrane37 – 6327Helical; Name=1; By similarity
Topological domain64 – 729Cytoplasmic By similarity
Transmembrane73 – 9119Helical; Name=2; By similarity
Topological domain92 – 11120Extracellular By similarity
Transmembrane112 – 13322Helical; Name=3; By similarity
Topological domain134 – 15522Cytoplasmic By similarity
Transmembrane156 – 17823Helical; Name=4; By similarity
Topological domain179 – 20325Extracellular By similarity
Transmembrane204 – 22522Helical; Name=5; By similarity
Topological domain226 – 29267Cytoplasmic By similarity
Transmembrane293 – 31422Helical; Name=6; By similarity
Topological domain315 – 32612Extracellular By similarity
Transmembrane327 – 34721Helical; Name=7; By similarity
Topological domain348 – 40861Cytoplasmic By similarity
Region198 – 21215Agonist and antagonist binding By similarity
Region305 – 3128Agonist and antagonist binding By similarity
Region332 – 3365Agonist and antagonist binding By similarity

Sites

Binding site1171Agonist or antagonist By similarity
Binding site1221Agonist or antagonist By similarity

Amino acid modifications

Lipidation3611S-palmitoyl cysteine By similarity
Glycosylation81N-linked (GlcNAc...) Potential
Glycosylation261N-linked (GlcNAc...) Potential
Disulfide bond110 ↔ 196 By similarity
Disulfide bond189 ↔ 195 By similarity

Natural variations

Natural variant641W → R. Ref.5 Ref.8 Ref.9 Ref.10 Ref.11
Corresponds to variant rs4994 [ dbSNP | Ensembl ].
VAR_003456
Natural variant2491E → K.
Corresponds to variant rs28364012 [ dbSNP | Ensembl ].
VAR_029205
Natural variant2651T → M. Ref.11
Corresponds to variant rs4995 [ dbSNP | Ensembl ].
VAR_014166
Natural variant3531R → C. Ref.5
Corresponds to variant rs36031925 [ dbSNP | Ensembl ].
VAR_025102

Sequences

Sequence LengthMass (Da)Tools
P13945 [UniParc].

Last modified February 1, 1994. Version 3.
Checksum: E98BD6C130DD977B

FASTA40843,519
        10         20         30         40         50         60 
MAPWPHENSS LAPWPDLPTL APNTANTSGL PGVPWEAALA GALLALAVLA TVGGNLLVIV 

        70         80         90        100        110        120 
AIAWTPRLQT MTNVFVTSLA AADLVMGLLV VPPAATLALT GHWPLGATGC ELWTSVDVLC 

       130        140        150        160        170        180 
VTASIETLCA LAVDRYLAVT NPLRYGALVT KRCARTAVVL VWVVSAAVSF APIMSQWWRV 

       190        200        210        220        230        240 
GADAEAQRCH SNPRCCAFAS NMPYVLLSSS VSFYLPLLVM LFVYARVFVV ATRQLRLLRG 

       250        260        270        280        290        300 
ELGRFPPEES PPAPSRSLAP APVGTCAPPE GVPACGRRPA RLLPLREHRA LCTLGLIMGT 

       310        320        330        340        350        360 
FTLCWLPFFL ANVLRALGGP SLVPGPAFLA LNWLGYANSA FNPLIYCRSP DFRSAFRRLL 

       370        380        390        400 
CRCGRRLPPE PCAAARPALF PSGVPAARSS PAQPRLCQRL DGASWGVS 

« Hide

References

« Hide 'large scale' references
[1]"Molecular characterization of the human beta 3-adrenergic receptor."
Emorine L.J., Marullo S., Briend-Sutren M.-M., Patey G., Tate K., Delavier-Klutchko C., Strosberg A.D.
Science 245:1118-1121(1989) [PubMed: 2570461] [Abstract]
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: 8389293] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], SEQUENCE REVISION.
[3]"Molecular cloning of a human beta 3-adrenergic receptor cDNA."
Lelias J.M., Kaghad M., Rodriguez M., Chalon P., Bonnin J., Dupre I., Delpech B., Bensaid M., Lefur G., Ferrara P., Caput D.
FEBS Lett. 324:127-130(1993) [PubMed: 8389717] [Abstract]
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: 15489334] [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: 1336117] [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: 7609752] [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: 8721782] [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: 8641219] [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: 10391210] [Abstract]
Cited for: VARIANTS ARG-64 AND MET-265.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
IPIIPI00011286.
PIRI57941.
QRHUBE. S33751.
RefSeqNP_000016.1. NM_000025.2.
UniGeneHs.2549.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2CDWmodel-A1-408[»]
ProteinModelPortalP13945.
SMRP13945. Positions 32-361.
ModBaseSearch...

Protein-protein interaction databases

STRINGP13945.

Protein family/group databases

GPCRDBSearch...

Polymorphism databases

DMDM461604.

Proteomic databases

PRIDEP13945.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000345060; ENSP00000343782; ENSG00000188778.
GeneID155.
KEGGhsa:155.
UCSCuc003xkr.1. human.

Organism-specific databases

CTD155.
GeneCardsGC08M037822.
H-InvDBHIX0034321.
HGNCHGNC:288. ADRB3.
MIM109691. gene.
neXtProtNX_P13945.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG11474.
GeneTreeENSGT00590000082831.
HOGENOMHBG445348.
HOVERGENHBG106962.
InParanoidP13945.
OMATNPLRYG.
OrthoDBEOG4NKBVZ.
PhylomeDBP13945.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressP13945.
BgeeP13945.
CleanExHS_ADRB3.
GenevestigatorP13945.
GermOnlineENSG00000188778. Homo sapiens.

Family and domain databases

InterProIPR000276. 7TM_GPCR_Rhodpsn.
IPR000681. Adrgc_rcpt_B3.
IPR002233. Adrnrgc_rcpt.
IPR017452. GPCR_Rhodpsn_supfam.
[Graphical view]
KOK04143.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR01103. ADRENERGICR.
PR00563. ADRENRGCB3AR.
PR00237. GPCRRHODOPSN.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

DrugBankDB00368. Norepinephrine.
DB00960. Pindolol.
DB00571. Propranolol.
NextBio617.
SOURCESearch...

Entry information

Entry nameADRB3_HUMAN
AccessionPrimary (citable) accession number: P13945
Secondary accession number(s): Q4JFT4
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: February 1, 1994
Last modified: January 25, 2012
This is version 134 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

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Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families