P13945 (ADRB3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Beta-3 adrenergic receptor

Alternative name(s):
Beta-3 adrenoreceptor
Short name=Beta-3 adrenoceptor

Gene names

Name:	ADRB3
Synonyms:	ADRB3R, B3AR

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	408 AA.
Sequence status	Complete.
Protein existence	Evidence 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 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.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Diabetes mellitus Obesity
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of adenylate cyclase activity Inferred from direct assay PubMed 15123695. Source: HGNC adenylate cyclase-activating G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: Compara adenylate cyclase-modulating G-protein coupled receptor signaling pathway Traceable author statement PubMed 1718744. Source: ProtInc aging Inferred from electronic annotation. Source: Compara brown fat cell differentiation Inferred from electronic annotation. Source: Compara carbohydrate metabolic process Traceable author statement Ref.1. Source: ProtInc diet induced thermogenesis Inferred from electronic annotation. Source: Compara eating behavior Inferred from electronic annotation. Source: Compara energy reserve metabolic process Traceable author statement PubMed 1718744. Source: ProtInc heat generation Inferred from electronic annotation. Source: Compara negative regulation of multicellular organism growth Inferred from electronic annotation. Source: Compara positive regulation of MAPK cascade Inferred from direct assay PubMed 15123695. Source: HGNC response to antibiotic Inferred from electronic annotation. Source: Compara response to cold Inferred from electronic annotation. Source: Compara vasodilation by norepinephrine-epinephrine involved in regulation of systemic arterial blood pressure Inferred from electronic annotation. Source: Compara
Cellular_component	integral to plasma membrane Traceable author statement PubMed 1718744. Source: ProtInc nucleus Inferred from electronic annotation. Source: Compara receptor complex Inferred from direct assay PubMed 15123695. Source: HGNC
Molecular_function	beta3-adrenergic receptor activity Inferred from mutant phenotype PubMed 9892244. Source: HGNC epinephrine binding Inferred from electronic annotation. Source: Compara protein homodimerization activity Inferred from direct assay PubMed 15123695. Source: HGNC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 408	408	Beta-3 adrenergic receptor		PRO_0000069143
Regions
	Topological domain	1 – 36	36	Extracellular By similarity
	Transmembrane	37 – 63	27	Helical; Name=1; By similarity
	Topological domain	64 – 72	9	Cytoplasmic By similarity
	Transmembrane	73 – 91	19	Helical; Name=2; By similarity
	Topological domain	92 – 111	20	Extracellular By similarity
	Transmembrane	112 – 133	22	Helical; Name=3; By similarity
	Topological domain	134 – 155	22	Cytoplasmic By similarity
	Transmembrane	156 – 178	23	Helical; Name=4; By similarity
	Topological domain	179 – 203	25	Extracellular By similarity
	Transmembrane	204 – 225	22	Helical; Name=5; By similarity
	Topological domain	226 – 292	67	Cytoplasmic By similarity
	Transmembrane	293 – 314	22	Helical; Name=6; By similarity
	Topological domain	315 – 326	12	Extracellular By similarity
	Transmembrane	327 – 347	21	Helical; Name=7; By similarity
	Topological domain	348 – 408	61	Cytoplasmic By similarity
	Region	198 – 212	15	Agonist and antagonist binding By similarity
	Region	305 – 312	8	Agonist and antagonist binding By similarity
	Region	332 – 336	5	Agonist and antagonist binding By similarity
Sites
	Binding site	117	1	Agonist or antagonist By similarity
	Binding site	122	1	Agonist or antagonist By similarity
Amino acid modifications
	Lipidation	361	1	S-palmitoyl cysteine By similarity
	Glycosylation	8	1	N-linked (GlcNAc...) Potential
	Glycosylation	26	1	N-linked (GlcNAc...) Potential
	Disulfide bond	110 ↔ 196		By similarity
	Disulfide bond	189 ↔ 195		By similarity
Natural variations
	Natural variant	64	1	W → R. Ref.5 Ref.8 Ref.9 Ref.10 Ref.11 Corresponds to variant rs4994 [ dbSNP | Ensembl ].		VAR_003456
	Natural variant	249	1	E → K. Corresponds to variant rs28364012 [ dbSNP | Ensembl ].		VAR_029205
	Natural variant	265	1	T → M. Ref.11 Corresponds to variant rs4995 [ dbSNP | Ensembl ].		VAR_014166
	Natural variant	353	1	R → C. Ref.5 Corresponds to variant rs36031925 [ dbSNP | Ensembl ].		VAR_025102

Sequences

	Sequence		Length	Mass (Da)
	P13945 [UniParc]. Last modified February 1, 1994. Version 3. Checksum: E98BD6C130DD977B	FASTA	408	43,519
	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

References

	« Hide 'large scale' referencesShow '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [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.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

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.

IPI

IPI00011286.

PIR

I57941.
QRHUBE. S33751.

RefSeq

NP_000016.1. NM_000025.2.

UniGene

Hs.2549.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CDW	model	-	A	1-408	[»]

ProteinModelPortal

P13945.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000343782.

Protein family/group databases

GPCRDB

Search...

Polymorphism databases

DMDM

461604.

Proteomic databases

PaxDb

P13945.

PRIDE

P13945.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000345060; ENSP00000343782; ENSG00000188778.

GeneID

155.

KEGG

hsa:155.

UCSC

uc003xkr.2. human.

Organism-specific databases

CTD

155.

GeneCards

GC08M037822.

HGNC

HGNC:288. ADRB3.

MIM

109691. gene.

neXtProt

NX_P13945.

PharmGKB

PA24598.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG262978.

HOGENOM

HOG000239242.

HOVERGEN

HBG106962.

InParanoid

P13945.

KO

K04143.

OMA

APIMSKW.

OrthoDB

EOG4NKBVZ.

PhylomeDB

P13945.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P13945.

Bgee

P13945.

CleanEx

HS_ADRB3.

Genevestigator

P13945.

GermOnline

ENSG00000188778. Homo sapiens.

Family and domain databases

InterPro

IPR000681. Adrgc_rcpt_B3.
IPR002233. Adrnrgc_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]

Pfam

PF00001. 7tm_1. 1 hit.
[Graphical view]

PRINTS

PR01103. ADRENERGICR.
PR00563. ADRENRGCB3AR.
PR00237. GPCRRHODOPSN.

PROSITE

PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P13945.

ChEMBL

CHEMBL246.

DrugBank

DB00368. Norepinephrine.
DB00960. Pindolol.
DB00571. Propranolol.

GenomeRNAi

155.

NextBio

617.

SOURCE

Search...

Entry information

Entry name

ADRB3_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 148 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.