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P08588 (ADRB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Beta-1 adrenergic receptor
Alternative name(s):
Beta-1 adrenoreceptor
Short name=Beta-1 adrenoceptor
Gene names
Name:ADRB1
Synonyms:ADRB1R, B1AR
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length477 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MAGI2Q86UL82EBI-991009,EBI-311035
MAGI3Q5TCQ95EBI-991009,EBI-310506

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 477477Beta-1 adrenergic receptor
PRO_0000069118

Regions

Topological domain1 – 5555Extracellular By similarity
Transmembrane56 – 8429Helical; Name=1; By similarity
Topological domain85 – 939Cytoplasmic By similarity
Transmembrane94 – 12027Helical; Name=2; By similarity
Topological domain121 – 13212Extracellular By similarity
Transmembrane133 – 15422Helical; Name=3; By similarity
Topological domain155 – 17218Cytoplasmic By similarity
Transmembrane173 – 19624Helical; Name=4; By similarity
Topological domain197 – 22226Extracellular By similarity
Transmembrane223 – 24826Helical; Name=5; By similarity
Topological domain249 – 31971Cytoplasmic By similarity
Transmembrane320 – 34930Helical; Name=6; By similarity
Topological domain350 – 3545Extracellular By similarity
Transmembrane355 – 37723Helical; Name=7; By similarity
Topological domain378 – 477100Cytoplasmic By similarity
Region218 – 23215Agonist and antagonist binding By similarity
Region337 – 3448Agonist and antagonist binding By similarity
Region363 – 3675Agonist and antagonist binding By similarity
Motif474 – 4774PDZ-Binding

Sites

Binding site1381Agonist or antagonist By similarity
Binding site1431Agonist or antagonist By similarity

Amino acid modifications

Modified residue3121Phosphoserine; by PKA Potential
Modified residue4121Phosphoserine; by PKA Potential
Lipidation3921S-palmitoyl cysteine By similarity
Glycosylation151N-linked (GlcNAc...) Probable
Disulfide bond131 ↔ 216 By similarity
Disulfide bond209 ↔ 215 By similarity

Natural variations

Natural variant261A → V.
Corresponds to variant rs34844626 [ dbSNP | Ensembl ].
VAR_055909
Natural variant291A → T.
Corresponds to variant rs35720093 [ dbSNP | Ensembl ].
VAR_055910
Natural variant311R → Q.
Corresponds to variant rs35230616 [ dbSNP | Ensembl ].
VAR_055911
Natural variant491S → 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 variant3891R → G Reduced binding to G proteins. Ref.2 Ref.3 Ref.5 Ref.7
Corresponds to variant rs1801253 [ dbSNP | Ensembl ].
VAR_009880
Natural variant3891R → L. Ref.3
VAR_018742
Natural variant3991R → H.
Corresponds to variant rs36052953 [ dbSNP | Ensembl ].
VAR_055912
Natural variant4051H → Y.
Corresponds to variant rs35705839 [ dbSNP | Ensembl ].
VAR_055913

Experimental info

Mutagenesis4741E → A or D: Loss of interaction with GOPC. Ref.6
Mutagenesis4741E → K: Loss of interaction with GOPC; when associated with A-477. Ref.6
Mutagenesis4751S → A: Loss of interaction with GOPC. Ref.6
Mutagenesis4751S → T: Partial loss of interaction with GOPC. Ref.6
Mutagenesis4761K → A: Partial loss of interaction with GOPC. Ref.6
Mutagenesis4771V → A, F, L, I or M: Loss of interaction with GOPC. Ref.6

Sequences

Sequence LengthMass (Da)Tools
P08588 [UniParc].

Last modified June 7, 2004. Version 2.
Checksum: 0950F2684E4721B8

FASTA47751,323
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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

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.
IPIIPI00029278.
PIRQRHUB1. A39911.
RefSeqNP_000675.1. NM_000684.2.
UniGeneHs.99913.

3D structure databases

ProteinModelPortalP08588.
SMRP08588. Positions 51-391.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-36294N.
IntActP08588. 9 interactions.
MINTMINT-208845.
STRINGP08588.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP08588.

Polymorphism databases

DMDM48429211.

Proteomic databases

PRIDEP08588.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000369295; ENSP00000358301; ENSG00000043591.
GeneID153.
KEGGhsa:153.

Organism-specific databases

CTD153.
GeneCardsGC10P115793.
H-InvDBHIX0035626.
HGNCHGNC:285. ADRB1.
MIM109630. gene.
607276. phenotype.
neXtProtNX_P08588.
PharmGKBPA38.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG14235.
GeneTreeENSGT00590000082831.
HOGENOMHBG445348.
HOVERGENHBG106962.
InParanoidP08588.
OrthoDBEOG4WQ12W.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressP08588.
BgeeP08588.
CleanExHS_ADRB1.
GenevestigatorP08588.
GermOnlineENSG00000043591. Homo sapiens.

Family and domain databases

InterProIPR000276. 7TM_GPCR_Rhodpsn.
IPR000507. Adrgc_rcpt_B1.
IPR002233. Adrnrgc_rcpt.
IPR017452. GPCR_Rhodpsn_supfam.
[Graphical view]
KOK04141.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR01103. ADRENERGICR.
PR00561. ADRENRGCB1AR.
PR00237. GPCRRHODOPSN.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

DrugBankDB01193. 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.
SOURCESearch...

Entry information

Entry nameADRB1_HUMAN
AccessionPrimary (citable) accession number: P08588
Secondary accession number(s): B0LPE2 expand/collapse secondary AC list , 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 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.

Relevant documents

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families