Reviewed,
UniProtKB/Swiss-Prot P08588 (ADRB1_HUMAN)
Last modified
February 9, 2010.
Version 116.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Beta-1 adrenergic receptor Alternative name(s): Beta-1 adrenoreceptor Short name=Beta-1 adrenoceptor | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| 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. |
Ontologies
| Keywords | |
|---|---|
| Cellular component | Cell membrane Membrane |
| Coding sequence diversity | Polymorphism |
| Domain | Transmembrane |
| Molecular function | G-protein coupled receptor Receptor Transducer |
| PTM | Disulfide bond Glycoprotein Lipoprotein Palmitate Phosphoprotein |
| Technical term | Complete proteome |
| Gene Ontology (GO) | |
| Cellular component | integral to plasma membrane Ref.7 Traceable author statement. Source: ProtInc |
| Molecular function | beta1-adrenergic receptor activity Ref.7 Traceable author statement. Source: ProtInc |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| Dlg1 | Q62696 | 1 | EBI-991009,EBI-389325 | From a different organism. |
| Dlg4 | P31016 | 1 | EBI-991009,EBI-375655 | From a different organism. |
| Gipc1 | Q9Z254 | 1 | EBI-991009,EBI-991162 | From a different organism. |
| GOPC | Q9HD26 | 1 | EBI-991009,EBI-349832 | |
| KIAA1634 | Q9HCD8 | 4 | EBI-991009,EBI-310506 | |
| MAGI1 | Q96QZ7 | 1 | EBI-991009,EBI-924464 | |
| MAGI2 | Q86UL8 | 1 | EBI-991009,EBI-311035 |
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 | 1 By similarity | ||||||||
| Topological domain | 85 – 93 | 9 | Cytoplasmic By similarity | ||||||||
| Transmembrane | 94 – 120 | 27 | 2 By similarity | ||||||||
| Topological domain | 121 – 132 | 12 | Extracellular By similarity | ||||||||
| Transmembrane | 133 – 154 | 22 | 3 By similarity | ||||||||
| Topological domain | 155 – 172 | 18 | Cytoplasmic By similarity | ||||||||
| Transmembrane | 173 – 196 | 24 | 4 By similarity | ||||||||
| Topological domain | 197 – 222 | 26 | Extracellular By similarity | ||||||||
| Transmembrane | 223 – 248 | 26 | 5 By similarity | ||||||||
| Topological domain | 249 – 319 | 71 | Cytoplasmic By similarity | ||||||||
| Transmembrane | 320 – 349 | 30 | 6 By similarity | ||||||||
| Topological domain | 350 – 354 | 5 | Extracellular By similarity | ||||||||
| Transmembrane | 355 – 377 | 23 | 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: dbSNP rs34844626. | VAR_055909 | |||||||
| Natural variant | 29 | 1 | A → T: dbSNP rs35720093. | VAR_055910 | |||||||
| Natural variant | 31 | 1 | R → Q: dbSNP rs35230616. | VAR_055911 | |||||||
| Natural variant | 49 | 1 | S → G Associated with high mean resting heart rate. dbSNP rs1801252. Ref.2 Ref.3 Ref.8 Ref.9 | VAR_009879 | |||||||
| Natural variant | 389 | 1 | R → G Reduced binding to G proteins. dbSNP rs1801253. Ref.2 Ref.3 Ref.5 Ref.7 | VAR_009880 | |||||||
| Natural variant | 389 | 1 | R → L | VAR_018742 | |||||||
| Natural variant | 399 | 1 | R → H: dbSNP rs36052953. | VAR_055912 | |||||||
| Natural variant | 405 | 1 | H → Y: dbSNP rs35705839. | 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
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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. 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. |
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. |
| UniGene | Hs.99913 |
3D structure databases | |
| SMR | P08588. Positions 56-257, 57-391. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | P08588. 7 interactions. |
| STRING | P08588. |
Protein family/group databases | |
| GPCRDB | Search... |
PTM databases | |
| PhosphoSite | P08588. |
Proteomic databases | |
| PRIDE | P08588. |
Genome annotation databases | |
| Ensembl | ENST00000369295; ENSP00000358301; ENSG00000043591; Homo sapiens. [Genome view] |
| GeneID | 153. |
| KEGG | hsa:153. |
Organism-specific databases | |
| CTD | 153. |
| GeneCards | GC10P115793. |
| H-InvDB | HIX0035626. |
| HGNC | HGNC:285. ADRB1. |
| MIM | 109630. gene. 607276. phenotype. |
| PharmGKB | PA38. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG14235. |
| HOGENOM | HBG445348. |
| HOVERGEN | P08588. |
| InParanoid | P08588. |
| OrthoDB | EOG92NMJH. |
Enzyme and pathway databases | |
| Reactome | REACT_14797. Signaling by GPCR. |
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] |
| 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 Resources | |
| 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 Q9UKG8 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| 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. | ||||||||
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 |

Clusters with


