Reviewed,
UniProtKB/Swiss-Prot P08913 (ADA2A_HUMAN)
Last modified
July 7, 2009.
Version 114.
History...
Clusters with 100%,
90%,
50% identity |
Documents (7) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Alpha-2A adrenergic receptor Alternative name(s): Alpha-2A adrenoreceptor Alpha-2A adrenoceptor Short name=Alpha-2AAR Alpha-2 adrenergic receptor subtype C10 | ||||
| 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 | 450 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol. |
| Subcellular location | |
| Sequence similarities | Belongs to the G-protein coupled receptor 1 family. |
Ontologies
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | |||||||||
Molecule processing | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 450 | 450 | Alpha-2A adrenergic receptor | PRO_0000069080 | ||||||||||
Regions | ||||||||||||||
| Topological domain | 1 – 33 | 33 | Extracellular By similarity | |||||||||||
| Transmembrane | 34 – 59 | 26 | 1 By similarity | |||||||||||
| Topological domain | 60 – 70 | 11 | Cytoplasmic By similarity | |||||||||||
| Transmembrane | 71 – 96 | 26 | 2 By similarity | |||||||||||
| Topological domain | 97 – 106 | 10 | Extracellular By similarity | |||||||||||
| Transmembrane | 107 – 129 | 23 | 3 By similarity | |||||||||||
| Topological domain | 130 – 151 | 22 | Cytoplasmic By similarity | |||||||||||
| Transmembrane | 152 – 172 | 21 | 4 By similarity | |||||||||||
| Topological domain | 173 – 194 | 22 | Extracellular By similarity | |||||||||||
| Transmembrane | 195 – 217 | 23 | 5 By similarity | |||||||||||
| Topological domain | 218 – 374 | 157 | Cytoplasmic By similarity | |||||||||||
| Transmembrane | 375 – 395 | 21 | 6 By similarity | |||||||||||
| Topological domain | 396 – 409 | 14 | Extracellular By similarity | |||||||||||
| Transmembrane | 410 – 429 | 20 | 7 By similarity | |||||||||||
| Topological domain | 430 – 450 | 21 | Cytoplasmic By similarity | |||||||||||
Sites | ||||||||||||||
| Site | 113 | 1 | Implicated in ligand binding | |||||||||||
| Site | 200 | 1 | Implicated in catechol agonist binding and receptor activation | |||||||||||
| Site | 204 | 1 | Implicated in catechol agonist binding and receptor activation | |||||||||||
Amino acid modifications | ||||||||||||||
| Modified residue | 297 | 1 | Phosphoserine Ref.16 | |||||||||||
| Modified residue | 298 | 1 | Phosphoserine Ref.16 | |||||||||||
| Modified residue | 299 | 1 | Phosphoserine Ref.16 | |||||||||||
| Lipidation | 442 | 1 | S-palmitoyl cysteine By similarity | |||||||||||
| Glycosylation | 10 | 1 | N-linked (GlcNAc...) Potential | |||||||||||
| Glycosylation | 14 | 1 | N-linked (GlcNAc...) Potential | |||||||||||
| Disulfide bond | 106 ↔ 188 | By similarity | ||||||||||||
Natural variations | ||||||||||||||
| Natural variant | 251 | 1 | N → K Rare polymorphism; frequency in Caucasians 0.004 and in African-Americans 0.05; 40% increase in agonist-promoted Gi coupling. dbSNP rs1800035. | VAR_014957 | ||||||||||
| Natural variant | 386 | 1 | C → S: dbSNP rs35658213. | VAR_055908 | ||||||||||
Experimental info | ||||||||||||||
| Mutagenesis | 79 | 1 | D → N: No change in binding affinity. eliminates guanine nucleotide-sensitive agonist binding. Ref.15 | |||||||||||
| Mutagenesis | 113 | 1 | D → N: No binding to yohimbine. Increase in adenylate cyclase activity. Ref.15 | |||||||||||
| Mutagenesis | 130 | 1 | D → N: Lower affinity for agonists. Eliminates guanine nucleotide-sensitive agonist binding. Ref.15 | |||||||||||
| Mutagenesis | 200 | 1 | S → A: Lower affinity for agonists. No change in guanine nucleotide-sensitive agonist binding. Ref.15 | |||||||||||
| Mutagenesis | 204 | 1 | S → A: Lower affinity for agonists. Reduced guanine nucleotide-sensitive agonist binding. Ref.15 | |||||||||||
| Mutagenesis | 412 | 1 | F → N: 350-fold reduced affinity for alpha-2 antagonist yohimbine, 3000-fold increase for beta-antagonist alprenolol. Ref.15 Ref.14 | |||||||||||
| Sequence conflict | 104 | 1 | A → T in AAA51664. Ref.1 | |||||||||||
| Sequence conflict | 124 | 1 | L → P Ref.13 | |||||||||||
| Sequence conflict | 157 | 1 | V → C in AAA51664. Ref.1 | |||||||||||
| Sequence conflict | 333 – 365 | 33 | PRRGP…RWRGR → RGAGRGRRGSGRRLQGRGRS ASGLPRRRAGAGG in AAA51664. Ref.1 | |||||||||||
| Sequence conflict | 333 – 365 | 33 | PRRGP…RWRGR → RGAGRGRRGSGRRLQGRGRS ASGLPRRRAGAGG in AAA51665. Ref.2 | |||||||||||
| Sequence conflict | 368 | 1 | R → L in AAA51664. Ref.1 | |||||||||||
Secondary structure | ||||||||||||||
Helix Strand Turn | ||||||||||||||
| Helix | 119 – 128 | 10 | ||||||||||||
| Helix | 130 – 139 | 10 | ||||||||||||
| Helix | 140 – 142 | 3 | ||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor." Kobilka B.K., Matsui H., Kobilka T.S., Yang-Feng T.L., Francke U., Caron M.G., Lefkowitz R.J., Regan J.W. Science 238:650-656(1987) [PubMed: 2823383] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PARTIAL PROTEIN SEQUENCE. Tissue: Platelet. |
| [2] | "Cloning, sequence analysis, and permanent expression of a human alpha 2-adrenergic receptor in Chinese hamster ovary cells. Evidence for independent pathways of receptor coupling to adenylate cyclase attenuation and activation." Fraser C.M., Arakawa S., McCombie W.R., Venter J.C. J. Biol. Chem. 264:11754-11761(1989) [PubMed: 2568356] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [3] | "Cloning, sequencing, and expression of the gene encoding the porcine alpha 2-adrenergic receptor. Allosteric modulation by Na+, H+, and amiloride analogs." Guyer C.A., Horstman D.A., Wilson A.L., Clark J.D., Kragoe E.J. Jr., Limbird L.E. J. Biol. Chem. 265:17307-17317(1990) [PubMed: 2170371] [Abstract] Cited for: SEQUENCE REVISION TO 333-365. |
| [4] | "An Asn to Lys polymorphism in the third intracellular loop of the human alpha 2A-adrenergic receptor imparts enhanced agonist-promoted Gi coupling." Small K.M., Forbes S.L., Brown K.M., Liggett S.B. J. Biol. Chem. 275:38518-38523(2000) [PubMed: 10948191] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LYS-251. |
| [5] | "Complex haplotypes derived from noncoding polymorphisms of the intronless alpha-2A-adrenergic gene diversify receptor expression." Small K.M., Brown K.M., Seman C.A., Theiss C.T., Liggett S.B. Proc. Natl. Acad. Sci. U.S.A. 103:5472-5477(2006) [PubMed: 16567612] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LYS-251. |
| [6] | "Cloning and expression of human alpha-2A adrenergic receptor in SY5Y cells." Mao Z.-M., Tang K., Li B.-M., Jing N.-H. Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
| [7] | "A search for genetic variability in the human alpha-2 adrenergic receptor on chromosome 10." Castellano M., Giacche' M., Rossi F., Rivadossi F., Perani C., Beschi M., Agabiti Rosei E. Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [8] | "Human alpha-2A adrenergic receptor gene and the genotype of -1296 nucleotide and motionsickness." Liu L., Yuan L. Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [9] | SeattleSNPs variation discovery resource Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LYS-251. |
| [10] | NHLBI resequencing and genotyping service (RS&G) Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [11] | "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]. |
| [12] | "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]. Tissue: PNS and Testis. |
| [13] | "Identification of an additional gene belonging to the alpha 2 adrenergic receptor family in the human genome by PCR." Chhajlani V., Rangel N., Uhlen S., Wikberg J.E.S. FEBS Lett. 280:241-244(1991) [PubMed: 1849485] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 77-209. |
| [14] | "A point mutation in the seventh hydrophobic domain of the alpha 2 adrenergic receptor increases its affinity for a family of beta receptor antagonists." Suryanarayana S., Daunt D.A., von Zastrow M., Kobilka B.K. J. Biol. Chem. 266:15488-15492(1991) [PubMed: 1678390] [Abstract] Cited for: MUTAGENESIS OF PHE-412. |
| [15] | "Site-directed mutagenesis of alpha 2a-adrenergic receptors: Identification of amino acids involved in ligand binding and receptor activation by agonists." Wang C.-D., Buck M.A., Fraser C.M. Mol. Pharmacol. 40:168-179(1991) [PubMed: 1678850] [Abstract] Cited for: MUTAGENESIS OF ASPARTIC ACID AND SERINE RESIDUES. |
| [16] | "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-297; SER-298 AND SER-299, MASS SPECTROMETRY. Tissue: Epithelium. |
| [17] | "NMR structure of the second intracellular loop of the alpha 2A adrenergic receptor: evidence for a novel cytoplasmic helix." Chung D.A., Zuiderweg E.R.P., Fowler C.B., Soyer O.S., Mosberg H.I., Neubig R.R. Biochemistry 41:3596-3604(2002) [PubMed: 11888275] [Abstract] Cited for: STRUCTURE BY NMR OF 118-149, PROBABLE TOPOLOGY. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M18415 Genomic DNA. Translation: AAA51664.1. M23533 Genomic DNA. Translation: AAA51665.1. AF281308 Genomic DNA. Translation: AAF91441.1. AF316894 Genomic DNA. Translation: AAK01634.1. DQ149926 Genomic DNA. Translation: AAZ73101.1. AF284095 mRNA. Translation: AAK26743.1. AF262016 Genomic DNA. Translation: AAG00447.2. AY032736 Genomic DNA. Translation: AAK51162.1. DQ285607 Genomic DNA. Translation: ABB72683.1. EU332846 Genomic DNA. Translation: ABY87535.1. AL158163 Genomic DNA. Translation: CAH72817.1. BC035047 mRNA. Translation: AAH35047.1. BC050414 mRNA. Translation: AAH50414.4. | |||||||||||||||||||||||||||||||
| IPI | IPI00797870. | ||||||||||||||||||||||||||||||
| PIR | A34169. | ||||||||||||||||||||||||||||||
| RefSeq | NP_000672.3. | ||||||||||||||||||||||||||||||
| UniGene | Hs.249159 | ||||||||||||||||||||||||||||||
3D structure databases | |||||||||||||||||||||||||||||||
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| ModBase | Search... | ||||||||||||||||||||||||||||||
Protein family/group databases | |||||||||||||||||||||||||||||||
| GPCRDB | Search... | ||||||||||||||||||||||||||||||
PTM databases | |||||||||||||||||||||||||||||||
| PhosphoSite | P08913. | ||||||||||||||||||||||||||||||
Proteomic databases | |||||||||||||||||||||||||||||||
| PRIDE | P08913. | ||||||||||||||||||||||||||||||
Genome annotation databases | |||||||||||||||||||||||||||||||
| Ensembl | ENSG00000150594. Homo sapiens. [Contig view] | ||||||||||||||||||||||||||||||
| GeneID | 150. | ||||||||||||||||||||||||||||||
| KEGG | hsa:150. | ||||||||||||||||||||||||||||||
| UCSC | uc001kzo.1. human. | ||||||||||||||||||||||||||||||
Organism-specific databases | |||||||||||||||||||||||||||||||
| GeneCards | GC10P112826. | ||||||||||||||||||||||||||||||
| H-InvDB | HIX0025918. | ||||||||||||||||||||||||||||||
| HGNC | HGNC:281. ADRA2A. | ||||||||||||||||||||||||||||||
| MIM | 104210. gene. | ||||||||||||||||||||||||||||||
| PharmGKB | PA35. | ||||||||||||||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||||||||||||||
| HOGENOM | P08913. | ||||||||||||||||||||||||||||||
| HOVERGEN | P08913. | ||||||||||||||||||||||||||||||
| OMA | P08913. QLNGAPG. | ||||||||||||||||||||||||||||||
Enzyme and pathway databases | |||||||||||||||||||||||||||||||
| Reactome | REACT_14797. Signaling by GPCR. | ||||||||||||||||||||||||||||||
Gene expression databases | |||||||||||||||||||||||||||||||
| ArrayExpress | P08913. | ||||||||||||||||||||||||||||||
| Bgee | P08913. | ||||||||||||||||||||||||||||||
| CleanEx | HS_ADRA2A. | ||||||||||||||||||||||||||||||
| GermOnline | ENSG00000150594. Homo sapiens. | ||||||||||||||||||||||||||||||
Family and domain databases | |||||||||||||||||||||||||||||||
| InterPro | IPR000276. 7TM_GPCR_Rhodpsn. IPR001946. Adren_rcpt_A2A. IPR015695. Adren_rcpt_A2A/B/C. IPR002233. Adrnrgc_rcpt. IPR017452. GPCR_Rhodpsn_supfam. [Graphical view] | ||||||||||||||||||||||||||||||
| PANTHER | PTHR19266:SF56. Alpha-2A_Recept. 1 hit. | ||||||||||||||||||||||||||||||
| Pfam | PF00001. 7tm_1. 1 hit. [Graphical view] | ||||||||||||||||||||||||||||||
| PRINTS | PR01103. ADRENERGICR. PR00558. ADRENRGCA2AR. 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 | DB00321. Amitriptyline. DB00182. Amphetamine. DB00964. Apraclonidine. DB00865. Benzphetamine. DB00217. Bethanidine. DB00484. Brimonidine. DB00575. Clonidine. DB04840. Debrisoquin. DB00633. Dexmedetomidine. DB00449. Dipivefrin. DB00751. Epinastine. DB00696. Ergotamine. DB00800. Fenoldopam. DB00629. Guanabenz. DB00226. Guanadrel Sulfate. DB01170. Guanethidine. DB01018. Guanfacine. DB04948. Lofexidine. DB00968. Methyldopa. DB06148. Mianserin. DB00370. Mirtazapine. DB00368. Norepinephrine. DB00935. Oxymetazoline. DB00692. Phentolamine. DB00397. Phenylpropanolamine. DB00852. Pseudoephedrine. DB00697. Tizanidine. DB00656. Trazodone. DB01392. Yohimbine. | ||||||||||||||||||||||||||||||
| NextBio | 595. | ||||||||||||||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||||||||||||||
Entry information
| Entry name | ADA2A_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P08913 Secondary accession number(s): B0LPF6 Q9BZK1 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
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 |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


