P08588 (ADRB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Beta-1 adrenergic receptor

Alternative name(s):
Beta-1 adrenoreceptor
Short name=Beta-1 adrenoceptor

Gene names

Name:	ADRB1
Synonyms:	ADRB1R, B1AR

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	477 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity.
Subunit structure	Interacts with GOPC, MAGI3 and DLG4. Ref.6
Subcellular location	Cell membrane; Multi-pass membrane protein. Note: Localized at the plasma membrane. Found in the Golgi upon GOPC overexpression. Ref.6
Domain	The PDZ domain-binding motif mediates competitive interactions with GOPC, MAGI3 and DLG4 and plays a role in subcellular location of the receptor.
Post-translational modification	Homologous desensitization of the receptor is mediated by its phosphorylation by beta-adrenergic receptor kinase.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB1 sub-subfamily.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	positive regulation of cAMP biosynthetic process Inferred from direct assay. Source: BHF-UCL
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	alpha-2A adrenergic receptor binding Inferred from physical interaction. Source: BHF-UCL beta1-adrenergic receptor activity Traceable author statement. Source: ProtInc protein heterodimerization activity Inferred from physical interaction. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MAGI2	Q86UL8	2	EBI-991009,EBI-311035
MAGI3	Q5TCQ9	5	EBI-991009,EBI-310506

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 477	477	Beta-1 adrenergic receptor		PRO_0000069118
Regions
	Topological domain	1 – 55	55	Extracellular By similarity
	Transmembrane	56 – 84	29	Helical; Name=1; By similarity
	Topological domain	85 – 93	9	Cytoplasmic By similarity
	Transmembrane	94 – 120	27	Helical; Name=2; By similarity
	Topological domain	121 – 132	12	Extracellular By similarity
	Transmembrane	133 – 154	22	Helical; Name=3; By similarity
	Topological domain	155 – 172	18	Cytoplasmic By similarity
	Transmembrane	173 – 196	24	Helical; Name=4; By similarity
	Topological domain	197 – 222	26	Extracellular By similarity
	Transmembrane	223 – 248	26	Helical; Name=5; By similarity
	Topological domain	249 – 319	71	Cytoplasmic By similarity
	Transmembrane	320 – 349	30	Helical; Name=6; By similarity
	Topological domain	350 – 354	5	Extracellular By similarity
	Transmembrane	355 – 377	23	Helical; Name=7; By similarity
	Topological domain	378 – 477	100	Cytoplasmic By similarity
	Region	218 – 232	15	Agonist and antagonist binding By similarity
	Region	337 – 344	8	Agonist and antagonist binding By similarity
	Region	363 – 367	5	Agonist and antagonist binding By similarity
	Motif	474 – 477	4	PDZ-Binding
Sites
	Binding site	138	1	Agonist or antagonist By similarity
	Binding site	143	1	Agonist or antagonist By similarity
Amino acid modifications
	Modified residue	312	1	Phosphoserine; by PKA Potential
	Modified residue	412	1	Phosphoserine; by PKA Potential
	Lipidation	392	1	S-palmitoyl cysteine By similarity
	Glycosylation	15	1	N-linked (GlcNAc...) Probable
	Disulfide bond	131 ↔ 216		By similarity
	Disulfide bond	209 ↔ 215		By similarity
Natural variations
	Natural variant	26	1	A → V. Corresponds to variant rs34844626 [ dbSNP | Ensembl ].		VAR_055909
	Natural variant	29	1	A → T. Corresponds to variant rs35720093 [ dbSNP | Ensembl ].		VAR_055910
	Natural variant	31	1	R → Q. Corresponds to variant rs35230616 [ dbSNP | Ensembl ].		VAR_055911
	Natural variant	49	1	S → G Associated with high mean resting heart rate. Ref.2 Ref.3 Ref.8 Ref.9 Corresponds to variant rs1801252 [ dbSNP | Ensembl ].		VAR_009879
	Natural variant	389	1	R → G Reduced binding to G proteins. Ref.2 Ref.3 Ref.5 Ref.7 Corresponds to variant rs1801253 [ dbSNP | Ensembl ].		VAR_009880
	Natural variant	389	1	R → L. Ref.3		VAR_018742
	Natural variant	399	1	R → H. Corresponds to variant rs36052953 [ dbSNP | Ensembl ].		VAR_055912
	Natural variant	405	1	H → Y. Corresponds to variant rs35705839 [ dbSNP | Ensembl ].		VAR_055913
Experimental info
	Mutagenesis	474	1	E → A or D: Loss of interaction with GOPC. Ref.6
	Mutagenesis	474	1	E → K: Loss of interaction with GOPC; when associated with A-477. Ref.6
	Mutagenesis	475	1	S → A: Loss of interaction with GOPC. Ref.6
	Mutagenesis	475	1	S → T: Partial loss of interaction with GOPC. Ref.6
	Mutagenesis	476	1	K → A: Partial loss of interaction with GOPC. Ref.6
	Mutagenesis	477	1	V → A, F, L, I or M: Loss of interaction with GOPC. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	P08588 [UniParc]. Last modified June 7, 2004. Version 2. Checksum: 0950F2684E4721B8	FASTA	477	51,323
	10 20 30 40 50 60 MGAGVLVLGA SEPGNLSSAA PLPDGAATAA RLLVPASPPA SLLPPASESP EPLSQQWTAG 70 80 90 100 110 120 MGLLMALIVL LIVAGNVLVI VAIAKTPRLQ TLTNLFIMSL ASADLVMGLL VVPFGATIVV 130 140 150 160 170 180 WGRWEYGSFF CELWTSVDVL CVTASIETLC VIALDRYLAI TSPFRYQSLL TRARARGLVC 190 200 210 220 230 240 TVWAISALVS FLPILMHWWR AESDEARRCY NDPKCCDFVT NRAYAIASSV VSFYVPLCIM 250 260 270 280 290 300 AFVYLRVFRE AQKQVKKIDS CERRFLGGPA RPPSPSPSPV PAPAPPPGPP RPAAAAATAP 310 320 330 340 350 360 LANGRAGKRR PSRLVALREQ KALKTLGIIM GVFTLCWLPF FLANVVKAFH RELVPDRLFV 370 380 390 400 410 420 FFNWLGYANS AFNPIIYCRS PDFRKAFQRL LCCARRAARR RHATHGDRPR ASGCLARPGP 430 440 450 460 470 PPSPGAASDD DDDDVVGATP PARLLEPWAG CNGGAAADSD SSLDEPCRPG FASESKV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the cDNA for the human beta 1-adrenergic receptor." Frielle T., Collins S., Daniel K.W., Caron M.G., Lefkowitz R.J., Kobilka B.K. Proc. Natl. Acad. Sci. U.S.A. 84:7920-7924(1987) [PubMed: 2825170] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	"Racial differences in the frequencies of cardiac beta(1)-adrenergic receptor polymorphisms: analysis of c145A>G and c1165G>C." Moore J.D., Mason D.A., Green S.A., Hsu J., Liggett S.B. Hum. Mutat. 14:271-271(1999) [PubMed: 10477438] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-49 AND GLY-389.
[3]	SeattleSNPs variation discovery resource Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-49; GLY-389 AND LEU-389.
[4]	NHLBI resequencing and genotyping service (RS&G) Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLY-389.
[6]	"Interaction with cystic fibrosis transmembrane conductance regulator-associated ligand (CAL) inhibits beta1-adrenergic receptor surface expression." He J., Bellini M., Xu J., Castleberry A.M., Hall R.A. J. Biol. Chem. 279:50190-50196(2004) [PubMed: 15358775] [Abstract] Cited for: INTERACTION WITH GOPC AND DLG4, MUTAGENESIS OF GLU-474; SER-475; LYS-476 AND VAL-477, SUBCELLULAR LOCATION.
[7]	"A gain-of-function polymorphism in a G-protein coupling domain of the human beta1-adrenergic receptor." Mason D.A., Moore J.D., Green S.A., Liggett S.B. J. Biol. Chem. 274:12670-12674(1999) [PubMed: 10212248] [Abstract] Cited for: VARIANT GLY-389.
[8]	"A novel polymorphism in the gene coding for the beta(1)-adrenergic receptor associated with survival in patients with heart failure." Borjesson M., Magnusson Y., Hjalmarson A., Andersson B. Eur. Heart J. 21:1853-1858(2000) [PubMed: 11052857] [Abstract] Cited for: VARIANT GLY-49.
[9]	"A polymorphism in the beta1 adrenergic receptor is associated with resting heart rate." Ranade K., Jorgenson E., Sheu W.H.-H., Pei D., Hsiung C.A., Chiang F.-T., Chen Y.-D.I., Pratt R., Olshen R.A., Curb D., Cox D.R., Botstein D., Risch N. Am. J. Hum. Genet. 70:935-942(2002) [PubMed: 11854867] [Abstract] Cited for: VARIANT GLY-49.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	J03019 mRNA. Translation: AAA51667.1. AF169006 Genomic DNA. Translation: AAD53696.1. AF169007 Genomic DNA. Translation: AAD53697.1. AY567837 Genomic DNA. Translation: AAS66983.1. EU332832 Genomic DNA. Translation: ABY87521.1. AL355543 Genomic DNA. Translation: CAI16920.1.
IPI	IPI00029278.
PIR	QRHUB1. A39911.
RefSeq	NP_000675.1. NM_000684.2.
UniGene	Hs.99913.
3D structure databases
ProteinModelPortal	P08588.
SMR	P08588. Positions 51-391.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-36294N.
IntAct	P08588. 9 interactions.
MINT	MINT-208845.
STRING	P08588.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P08588.
Polymorphism databases
DMDM	48429211.
Proteomic databases
PRIDE	P08588.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000369295; ENSP00000358301; ENSG00000043591.
GeneID	153.
KEGG	hsa:153.
Organism-specific databases
CTD	153.
GeneCards	GC10P115793.
H-InvDB	HIX0035626.
HGNC	HGNC:285. ADRB1.
MIM	109630. gene. 607276. phenotype.
neXtProt	NX_P08588.
PharmGKB	PA38.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG14235.
GeneTree	ENSGT00590000082831.
HOGENOM	HBG445348.
HOVERGEN	HBG106962.
InParanoid	P08588.
OrthoDB	EOG4WQ12W.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	P08588.
Bgee	P08588.
CleanEx	HS_ADRB1.
Genevestigator	P08588.
GermOnline	ENSG00000043591. Homo sapiens.
Family and domain databases
InterPro	IPR000276. 7TM_GPCR_Rhodpsn. IPR000507. Adrgc_rcpt_B1. IPR002233. Adrnrgc_rcpt. IPR017452. GPCR_Rhodpsn_supfam. [Graphical view]
KO	K04141.
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR01103. ADRENERGICR. PR00561. ADRENRGCB1AR. PR00237. GPCRRHODOPSN.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB01193. Acebutolol. DB00866. Alprenolol. DB01118. Amiodarone. DB01102. Arbutamine. DB00335. Atenolol. DB00195. Betaxolol. DB01295. Bevantolol. DB00612. Bisoprolol. DB01158. Bretylium. DB00521. Carteolol. DB01136. Carvedilol. DB01151. Desipramine. DB00841. Dobutamine. DB00988. Dopamine. DB00668. Epinephrine. DB00187. Esmolol. DB00221. Isoetharine. DB01064. Isoproterenol. DB00598. Labetalol. DB01210. Levobunolol. DB01214. Metipranolol. DB00264. Metoprolol. DB01203. Nadolol. DB00368. Norepinephrine. DB01580. Oxprenolol. DB01359. Penbutolol. DB00960. Pindolol. DB01297. Practolol. DB00571. Propranolol. DB00734. Risperidone. DB00373. Timolol. DB00246. Ziprasidone.
SOURCE	Search...

Entry information

Entry name

ADRB1_HUMAN

Accession

Primary (citable) accession number: P08588
Secondary accession number(s): B0LPE2 , Q5T5Y4, Q9UKG7, Q9UKG8

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	June 7, 2004
Last modified:	January 25, 2012
This is version 130 of the entry and version 2 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.