T3DB: Alpha-2A adrenergic receptor

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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
Organism	Human
Amino acid sequence	>lcl\|BSEQ0021255\|Alpha-2A adrenergic receptor MGSLQPDAGNASWNGTEAPGGGARATPYSLQVTLTLVCLAGLLMLLTVFGNVLVIIAVFT SRALKAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGKAWCEIYLALDVLFCTSS IVHLCAISLDRYWSITQAIEYNLKRTPRRIKAIIITVWVISAVISFPPLISIEKKGGGGG PQPAEPRCEINDQKWYVISSCIGSFFAPCLIMILVYVRIYQIAKRRTRVPPSRRGPDAVA APPGGTERRPNGLGPERSAGPGGAEAEPLPTQLNGAPGEPAPAGPRDTDALDLEESSSSD HAERPPGPRRPERGPRGKGKARASQVKPGDSLPRRGPGATGIGTPAAGPGEERVGAAKAS RWRGRQNREKRFTFVLAVVIGVFVVCWFPFFFTYTLTAVGCSVPRTLFKFFFWFGYCNSS LNPVIYTIFNHDFRRAFKKILCRGDRKRIV
Number of residues	450
Molecular Weight	48956.275
Theoretical pI	10.2
GO Classification	Functions protein heterodimerization activity thioesterase binding alpha-1B adrenergic receptor binding alpha-2C adrenergic receptor binding protein homodimerization activity protein kinase binding heterotrimeric G-protein binding alpha2-adrenergic receptor activity epinephrine binding norepinephrine binding Processes cell-cell signaling fear response Rho protein signal transduction thermoception platelet activation negative regulation of calcium ion transport cellular response to hormone stimulus regulation of vasoconstriction positive regulation of vasodilation negative regulation of norepinephrine secretion small molecule metabolic process activation of MAPK activity by adrenergic receptor signaling pathway female pregnancy activation of protein kinase B activity glucose homeostasis adenylate cyclase-inhibiting adrenergic receptor signaling pathway epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway movement of cell or subcellular component negative regulation of adrenergic receptor signaling pathway actin cytoskeleton organization negative regulation of epinephrine secretion negative regulation of adenylate cyclase activity negative regulation of calcium ion transmembrane transporter activity negative regulation of insulin secretion involved in cellular response to glucose stimulus positive regulation of MAP kinase activity negative regulation of calcium ion-dependent exocytosis positive regulation of cell migration negative regulation of uterine smooth muscle contraction acute inflammatory response phospholipase C-activating adrenergic receptor signaling pathway Ras protein signal transduction negative regulation of cAMP biosynthetic process signal transduction negative regulation of insulin secretion positive regulation of wound healing blood coagulation negative regulation of lipid catabolic process energy reserve metabolic process intestinal absorption DNA replication positive regulation of epidermal growth factor-activated receptor activity G-protein coupled receptor signaling pathway positive regulation of membrane protein ectodomain proteolysis positive regulation of potassium ion transport regulation of insulin secretion positive regulation of cytokine production positive regulation of cell proliferation activation of protein kinase activity Components integral component of plasma membrane cytoplasm basolateral plasma membrane synapse plasma membrane receptor complex
General Function	Thioesterase binding
Specific 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.
Pfam Domain Function	7tm_1 (PF00001 )
Transmembrane Regions	34-59 71-96 107-129 152-172 195-217 375-395 410-429
GenBank Protein ID	178196
UniProtKB ID	P08913
UniProtKB Entry Name	ADA2A_HUMAN
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
GenBank Gene ID	M23533
GeneCard ID	Not Available
GenAtlas ID	ADRA2A
HGNC ID	HGNC:281
Chromosome Location	10
Locus	10q24-q26
References	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. 2823383 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. 2568356 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. 2170371 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. 10948191 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. 16567612 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. 15164054 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. 15489334 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. 1849485 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. 1678390 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. 1678850 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. 23105096 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. 11888275