Alpha-2A adrenergic receptor

Details

Name
Alpha-2A adrenergic receptor
Synonyms
  • ADRA2R
  • ADRAR
  • Alpha-2 adrenergic receptor subtype C10
  • Alpha-2A adrenoceptor
  • Alpha-2A adrenoreceptor
  • Alpha-2AAR
Gene Name
ADRA2A
UniProtKB Entry
P08913Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0055723|Alpha-2A adrenergic receptor
MFRQEQPLAEGSFAPMGSLQPDAGNASWNGTEAPGGGARATPYSLQVTLTLVCLAGLLML
LTVFGNVLVIIAVFTSRALKAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGKAW
CEIYLALDVLFCTSSIVHLCAISLDRYWSITQAIEYNLKRTPRRIKAIIITVWVISAVIS
FPPLISIEKKGGGGGPQPAEPRCEINDQKWYVISSCIGSFFAPCLIMILVYVRIYQIAKR
RTRVPPSRRGPDAVAAPPGGTERRPNGLGPERSAGPGGAEAEPLPTQLNGAPGEPAPAGP
RDTDALDLEESSSSDHAERPPGPRRPERGPRGKGKARASQVKPGDSLPRRGPGATGIGTP
AAGPGEERVGAAKASRWRGRQNREKRFTFVLAVVIGVFVVCWFPFFFTYTLTAVGCSVPR
TLFKFFFWFGYCNSSLNPVIYTIFNHDFRRAFKKILCRGDRKRIV
Number of residues
465
Molecular Weight
50646.17
Theoretical pI
10.2
GO Classification
Processes
adenylate cyclase-activating adrenergic receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / adrenergic receptor signaling pathway / G protein-coupled receptor signaling pathway / positive regulation of cell population proliferation / positive regulation of epidermal growth factor receptor signaling pathway / positive regulation of MAPK cascade / presynaptic modulation of chemical synaptic transmission / receptor transactivation / vasodilation
Components
axon terminus / dopaminergic synapse / GABA-ergic synapse / glutamatergic synapse / neuronal cell body / postsynaptic density membrane / presynaptic active zone membrane
General 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
Specific Function
Alpha-1b adrenergic receptor binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
49-74 86-111 122-144 167-187 210-232 390-410 425-444
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0021256|Alpha-2A adrenergic receptor (ADRA2A)
ATGTTCCGCCAGGAGCAGCCGTTGGCCGAGGGCAGCTTTGCGCCCATGGGCTCCCTGCAG
CCGGACGCGGGCAACGCGAGCTGGAACGGGACCGAGGCGCCGGGGGGCGGCGCCCGGGCC
ACCCCTTACTCCCTGCAGGTGACGCTGACGCTGGTGTGCCTGGCCGGCCTGCTCATGCTG
CTCACCGTGTTCGGCAACGTGCTCGTCATCATCGCCGTGTTCACGAGCCGCGCGCTCAAG
GCGCCCCAAAACCTCTTCCTGGTGTCTCTGGCCTCGGCCGACATCCTGGTGGCCACGCTC
GTCATCCCTTTCTCGCTGGCCAACGAGGTCATGGGCTACTGGTACTTCGGCAAGGCTTGG
TGCGAGATCTACCTGGCGCTCGACGTGCTCTTCTGCACGTCGTCCATCGTGCACCTGTGC
GCCATCAGCCTGGACCGCTACTGGTCCATCACACAGGCCATCGAGTACAACCTGAAGCGC
ACGCCGCGCCGCATCAAGGCCATCATCATCACCGTGTGGGTCATCTCGGCCGTCATCTCC
TTCCCGCCGCTCATCTCCATCGAGAAGAAGGGCGGCGGCGGCGGCCCGCAGCCGGCCGAG
CCGCGCTGCGAGATCAACGACCAGAAGTGGTACGTCATCTCGTCGTGCATCGGCTCCTTC
TTCGCTCCCTGCCTCATCATGATCCTGGTCTACGTGCGCATCTACCAGATCGCCAAGCGT
CGCACCCGCGTGCCACCCAGCCGCCGGGGTCCGGACGCCGTCGCCGCGCCGCCGGGGGGC
ACCGAGCGCAGGCCCAACGGTCTGGGCCCCGAGCGCAGCGCGGGCCCGGGGGGCGCAGAG
GCCGAACCGCTGCCCACCCAGCTCAACGGCGCCCCTGGCGAGCCCGCGCCGGCCGGGCCG
CGCGACACCGACGCGCTGGACCTGGAGGAGAGCTCGTCTTCCGACCACGCCGAGCGGCCT
CCAGGGCCCCGCAGACCCGAGCGCGGTCCCCGGGGCAAAGGCAAGGCCCGAGCGAGCCAG
GTGAAGCCGGGCGACAGCCTGCCGCGGCGCGGGCCGGGGGCGACGGGGATCGGGACGCCG
GCTGCAGGGCCGGGGGAGGAGCGCGTCGGGGCTGCCAAGGCGTCGCGCTGGCGCGGGCGG
CAGAACCGCGAGAAGCGCTTCACGTTCGTGCTGGCCGTGGTCATCGGAGTGTTCGTGGTG
TGCTGGTTCCCCTTCTTCTTCACCTACACGCTCACGGCCGTCGGGTGCTCCGTGCCACGC
ACGCTCTTCAAATTCTTCTTCTGGTTCGGCTACTGCAACAGCTCGTTGAACCCGGTCATC
TACACCATCTTCAACCACGATTTCCGCCGCGCCTTCAAGAAGATCCTCTGTCGGGGGGAC
AGGAAGCGGATCGTGTGA
Chromosome Location
10
Locus
10q25.2
External Identifiers
ResourceLink
UniProtKB IDP08913
UniProtKB Entry NameADA2A_HUMAN
GenBank Protein ID178196
GenBank Gene IDM23533
GeneCard IDADRA2A
GenAtlas IDADRA2A
HGNC IDHGNC:281
PDB ID(s)1HLL, 1HO9, 1HOD, 1HOF, 6K42, 6KUX, 6KUY, 7EJ0, 7EJ8, 7EJA, 7EJK, 7W6P, 7W7E
KEGG IDhsa:150
IUPHAR/Guide To Pharmacology ID25
NCBI Gene ID150
General References
  1. Kobilka BK, Matsui H, Kobilka TS, Yang-Feng TL, Francke U, Caron MG, Lefkowitz RJ, Regan JW: Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor. Science. 1987 Oct 30;238(4827):650-6. [Article]
  2. Fraser CM, Arakawa S, McCombie WR, Venter JC: 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. J Biol Chem. 1989 Jul 15;264(20):11754-61. [Article]
  3. Guyer CA, Horstman DA, Wilson AL, Clark JD, Cragoe EJ Jr, Limbird LE: Cloning, sequencing, and expression of the gene encoding the porcine alpha 2-adrenergic receptor. Allosteric modulation by Na+, H+, and amiloride analogs. J Biol Chem. 1990 Oct 5;265(28):17307-17. [Article]
  4. Small KM, Forbes SL, Brown KM, Liggett SB: An asn to lys polymorphism in the third intracellular loop of the human alpha 2A-adrenergic receptor imparts enhanced agonist-promoted Gi coupling. J Biol Chem. 2000 Dec 8;275(49):38518-23. [Article]
  5. Small KM, Brown KM, Seman CA, Theiss CT, Liggett SB: Complex haplotypes derived from noncoding polymorphisms of the intronless alpha2A-adrenergic gene diversify receptor expression. Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5472-7. Epub 2006 Mar 27. [Article]
  6. Deloukas P, Earthrowl ME, Grafham DV, Rubenfield M, French L, Steward CA, Sims SK, Jones MC, Searle S, Scott C, Howe K, Hunt SE, Andrews TD, Gilbert JG, Swarbreck D, Ashurst JL, Taylor A, Battles J, Bird CP, Ainscough R, Almeida JP, Ashwell RI, Ambrose KD, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Bates K, Beasley H, Bray-Allen S, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Cahill P, Camire D, Carter NP, Chapman JC, Clark SY, Clarke G, Clee CM, Clegg S, Corby N, Coulson A, Dhami P, Dutta I, Dunn M, Faulkner L, Frankish A, Frankland JA, Garner P, Garnett J, Gribble S, Griffiths C, Grocock R, Gustafson E, Hammond S, Harley JL, Hart E, Heath PD, Ho TP, Hopkins B, Horne J, Howden PJ, Huckle E, Hynds C, Johnson C, Johnson D, Kana A, Kay M, Kimberley AM, Kershaw JK, Kokkinaki M, Laird GK, Lawlor S, Lee HM, Leongamornlert DA, Laird G, Lloyd C, Lloyd DM, Loveland J, Lovell J, McLaren S, McLay KE, McMurray A, Mashreghi-Mohammadi M, Matthews L, Milne S, Nickerson T, Nguyen M, Overton-Larty E, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter K, Rice CM, Rogosin A, Ross MT, Sarafidou T, Sehra HK, Shownkeen R, Skuce CD, 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 AP, Willey DL, Whitehead SL, Wilming L, Wray PW, Young L, Chen Y, Lovering RC, Moschonas NK, Siebert R, Fechtel K, Bentley D, Durbin R, Hubbard T, Doucette-Stamm L, Beck S, Smith DR, Rogers J: The DNA sequence and comparative analysis of human chromosome 10. Nature. 2004 May 27;429(6990):375-81. [Article]
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  8. Chhajlani V, Rangel N, Uhlen S, Wikberg JE: Identification of an additional gene belonging to the alpha 2 adrenergic receptor family in the human genome by PCR. FEBS Lett. 1991 Mar 25;280(2):241-4. [Article]
  9. Suryanarayana S, Daunt DA, Von Zastrow M, Kobilka BK: A point mutation in the seventh hydrophobic domain of the alpha 2 adrenergic receptor increases its affinity for a family of beta receptor antagonists. J Biol Chem. 1991 Aug 15;266(23):15488-92. [Article]
  10. Wang CD, Buck MA, Fraser CM: Site-directed mutagenesis of alpha 2A-adrenergic receptors: identification of amino acids involved in ligand binding and receptor activation by agonists. Mol Pharmacol. 1991 Aug;40(2):168-79. [Article]
  11. Li C, Fan Y, Lan TH, Lambert NA, Wu G: Rab26 modulates the cell surface transport of alpha2-adrenergic receptors from the Golgi. J Biol Chem. 2012 Dec 14;287(51):42784-94. doi: 10.1074/jbc.M112.410936. Epub 2012 Oct 26. [Article]
  12. Chung DA, Zuiderweg ER, Fowler CB, Soyer OS, Mosberg HI, Neubig RR: NMR structure of the second intracellular loop of the alpha 2A adrenergic receptor: evidence for a novel cytoplasmic helix. Biochemistry. 2002 Mar 19;41(11):3596-604. [Article]

Associated Data

Bio-Entities
Bio-EntityType
Alpha-2A adrenergic receptor (Humans)protein
primary
Alpha-2 adrenergic receptors (Humans)protein
Alpha adrenergic receptor (Humans)protein
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
DipivefrinapprovedyestargetagonistDetails
BrimonidineapprovedyestargetagonistDetails
ClonidineapprovedyestargetagonistDetails
Guanabenzapproved, investigationalyestargetagonistDetails
Dexmedetomidineapproved, vet_approvedyestargetagonistDetails
Benzphetamineapproved, illicityestargetagonistDetails
ApraclonidineapprovedyestargetagonistDetails
MethyldopaapprovedyestargetagonistDetails
Guanfacineapproved, investigationalyestargetagonistDetails
MirtazapineapprovedyestargetantagonistDetails
Trazodoneapproved, investigationalnotargetantagonistDetails
FenoldopamapprovedunknowntargetantagonistDetails
PseudoephedrineapprovedyestargetagonistDetails
Oxymetazolineapproved, investigationalyestargetagonistpartial agonistDetails
Yohimbineapproved, investigational, vet_approvedyestargetantagonistDetails
AmitriptylineapprovednotargetantagonistagonistDetails
4-Methoxyamphetamineexperimental, illicityestargetagonistDetails
NorepinephrineapprovedyestargetagonistDetails
Ergotamineapprovedunknowntargetpartial agonistDetails
DronedaroneapprovedyestargetantagonistDetails
Epinastineapproved, investigationalunknowntargetunknownDetails
Mianserinapproved, investigationalunknowntargetantagonistDetails
Lofexidineapproved, investigationalyestargetagonistDetails
Epicept NP-1investigationalunknowntargetDetails
Droxidopaapproved, investigationalyestargetagonistDetails
AsenapineapprovedunknowntargetantagonistDetails
OcaperidoneinvestigationalunknowntargetDetails
FlupirtineinvestigationalunknowntargetDetails
Xylometazolineapproved, investigationalyestargetagonistDetails
Bromocriptineapproved, investigational, withdrawnunknowntargetagonistDetails
Lisurideapproved, investigationalunknowntargetother/unknownDetails
CabergolineapprovedunknowntargetantagonistDetails
Pramipexoleapproved, investigationalunknowntargetagonistDetails
Apomorphineapproved, investigationalunknowntargetagonistDetails
PaliperidoneapprovedunknowntargetantagonistDetails
QuetiapineapprovedunknowntargetantagonistDetails
ZiprasidoneapprovedunknowntargetantagonistDetails
ClozapineapprovedunknowntargetantagonistDetails
Aripiprazoleapproved, investigationalnotargetantagonistDetails
Methotrimeprazineapproved, investigationalunknowntargetantagonistDetails
Periciazineapproved, investigationalyestargetantagonistDetails
Zuclopenthixolapproved, investigationalunknowntargetantagonistDetails
Nefazodoneapproved, withdrawnunknowntargetantagonistDetails
AmoxapineapprovedunknowntargetantagonistDetails
Tolazolineapproved, vet_approvedunknowntargetantagonistDetails
Dihydroergotamineapproved, investigationalunknowntargetagonistDetails
Naphazolineapproved, investigationalyestargetagonistDetails
PhenoxybenzamineapprovedyestargetantagonistDetails
Ephedra sinica rootnutraceuticalyestargetagonistDetails
Metamfetamineapproved, illicit, withdrawnyestargetagonistDetails
Epinephrineapproved, vet_approvedyestargetagonistDetails
Lurasidoneapproved, investigationalunknowntargetDetails
LoxapineapprovedunknowntargetbinderDetails
Carvedilolapproved, investigationalunknowntargetantagonistDetails
TrimipramineapprovedunknowntargetantagonistDetails
PrazosinapprovedunknowntargetbinderDetails
Moxonidineapproved, investigationalyestargetagonistDetails
Rilmenidineapproved, investigationalunknowntargetDetails
Lamotrigineapproved, investigationalunknowntargetinhibitorDetails
PirlindoleexperimentalunknowntargetantagonistDetails
PipamperoneinvestigationalunknowntargetantagonistDetails
RacepinephrineapprovedyestargetagonistDetails
PizotifenapprovedunknowntargetantagonistDetails
DL-MethylephedrineapprovedyestargetagonistDetails
Celiprololapproved, investigationalunknowntargetantagonistDetails
Aripiprazole lauroxilapproved, investigationalnotargetDetails
HaloperidolapprovedunknowntargetDetails
IloperidoneapprovedunknowntargetantagonistDetails
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineexperimentalyestargetinhibitorDetails
1,2,3,4-Tetrahydro-Isoquinoline-7-Sulfonic Acid AmideexperimentalyestargetinhibitorDetails
TramazolineinvestigationalyestargetinhibitorDetails
Medetomidineexperimental, vet_approvedyestargetinhibitorDetails
Tizanidineapproved, investigationalunknowntargetagonistDetails
BethanidineapprovedyestargetagonistDetails
Pergolideapproved, investigational, vet_approved, withdrawnunknowntargetagonistDetails
Chlorpromazineapproved, investigational, vet_approvedunknowntargetinhibitorDetails
AmoxapineapprovedunknowntargetantagonistDetails
NortriptylineapprovedunknowntargetantagonistDetails
Maprotilineapproved, investigationalunknowntargetantagonistDetails
Desipramineapproved, investigationalunknowntargetbinderDetails
CirazolineexperimentalyestargetantagonistDetails
EsmirtazapineinvestigationalunknowntargetantagonistDetails
LevonordefrinapprovedyestargetagonistDetails
TiaprideinvestigationalyestargetantagonistDetails
DosulepinapprovedyestargetantagonistDetails
SetiptilineexperimentalunknowntargetantagonistDetails
Phenylpropanolamineapproved, vet_approved, withdrawnunknowntargetDetails
EtoperidonewithdrawnunknowntargetantagonistDetails
LorpiprazoleapprovedyestargetantagonistDetails
Xylazinevet_approvedyestargetagonistDetails
Prochlorperazineapproved, vet_approvednotargetantagonistDetails
Paroxetineapproved, investigationalunknowntargetbinderDetails
Tramadolapproved, investigationalyestargetinducerDetails
EscitalopramapprovedunknowntargetinhibitorDetails
TetryzolineapprovedunknowntargetagonistDetails
Dihydroergotamineapproved, investigationalunknowntargetagonistDetails
PhentolamineapprovedunknowntargetantagonistDetails
MephentermineapprovedyestargetagonistDetails
Amphetamineapproved, illicit, investigationalunknowntargetagonistDetails
Moxisylyteapproved, investigationalyestargetantagonistDetails
AranidipineexperimentalunknowntargetagonistDetails
Indigotindisulfonic acidapproved, investigationalnotargetagonistDetails
Dihydroergocristineapproved, experimentalyestargetantagonistagonistDetails
Ergoloid mesylateapprovedyestargetantagonistagonistDetails
DihydroergocornineapprovedyestargetantagonistagonistDetails
DL-MethylephedrineapprovedyestargetagonistDetails
Ropiniroleapproved, investigationalunknowntargetantagonistDetails
Promethazineapproved, investigationalunknowntargetantagonistDetails
Dextroamphetamineapproved, illicitunknowntargetinhibitorinducerDetails