ADA2A_HUMAN
ID ADA2A_HUMAN Reviewed; 465 AA.
AC P08913; B0LPF6; Q2I8G2; Q2XN99; Q86TH8; Q9BZK1;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 11-DEC-2019, sequence version 4.
DT 03-AUG-2022, entry version 225.
DE RecName: Full=Alpha-2A adrenergic receptor {ECO:0000305};
DE AltName: Full=Alpha-2 adrenergic receptor subtype C10;
DE AltName: Full=Alpha-2A adrenoreceptor;
DE Short=Alpha-2A adrenoceptor;
DE Short=Alpha-2AAR;
GN Name=ADRA2A {ECO:0000312|HGNC:HGNC:281}; Synonyms=ADRA2R, ADRAR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2568356; DOI=10.1016/s0021-9258(18)80130-2;
RA Fraser C.M., Arakawa S., McCombie W.R., Venter J.C.;
RT "Cloning, sequence analysis, and permanent expression of a human alpha 2-
RT adrenergic receptor in Chinese hamster ovary cells. Evidence for
RT independent pathways of receptor coupling to adenylate cyclase attenuation
RT and activation.";
RL J. Biol. Chem. 264:11754-11761(1989).
RN [2]
RP SEQUENCE REVISION TO 333-365.
RX PubMed=2170371; DOI=10.1016/s0021-9258(17)44904-0;
RA Guyer C.A., Horstman D.A., Wilson A.L., Clark J.D., Kragoe E.J. Jr.,
RA Limbird L.E.;
RT "Cloning, sequencing, and expression of the gene encoding the porcine alpha
RT 2-adrenergic receptor. Allosteric modulation by Na+, H+, and amiloride
RT analogs.";
RL J. Biol. Chem. 265:17307-17317(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=16567612; DOI=10.1073/pnas.0601345103;
RA Small K.M., Brown K.M., Seman C.A., Theiss C.T., Liggett S.B.;
RT "Complex haplotypes derived from noncoding polymorphisms of the intronless
RT alpha-2A-adrenergic gene diversify receptor expression.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:5472-5477(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Mao Z.-M., Tang K., Li B.-M., Jing N.-H.;
RT "Cloning and expression of human alpha-2A adrenergic receptor in SY5Y
RT cells.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Castellano M., Giacche' M., Rossi F., Rivadossi F., Perani C., Beschi M.,
RA Agabiti Rosei E.;
RT "A search for genetic variability in the human alpha-2 adrenergic receptor
RT on chromosome 10.";
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Liu L., Yuan L.;
RT "Human alpha-2A adrenergic receptor gene and the genotype of -1296
RT nucleotide and motionsickness.";
RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LYS-266.
RG SeattleSNPs variation discovery resource;
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=PNS, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 7-465, AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Platelet;
RX PubMed=2823383; DOI=10.1126/science.2823383;
RA Kobilka B.K., Matsui H., Kobilka T.S., Yang-Feng T.L., Francke U.,
RA Caron M.G., Lefkowitz R.J., Regan J.W.;
RT "Cloning, sequencing, and expression of the gene coding for the human
RT platelet alpha 2-adrenergic receptor.";
RL Science 238:650-656(1987).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 16-465, AND VARIANT LYS-266.
RX PubMed=10948191; DOI=10.1074/jbc.m004550200;
RA Small K.M., Forbes S.L., Brown K.M., Liggett S.B.;
RT "An Asn to Lys polymorphism in the third intracellular loop of the human
RT alpha 2A-adrenergic receptor imparts enhanced agonist-promoted Gi
RT coupling.";
RL J. Biol. Chem. 275:38518-38523(2000).
RN [13]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 92-224.
RX PubMed=1849485; DOI=10.1016/0014-5793(91)80301-i;
RA Chhajlani V., Rangel N., Uhlen S., Wikberg J.E.S.;
RT "Identification of an additional gene belonging to the alpha 2 adrenergic
RT receptor family in the human genome by PCR.";
RL FEBS Lett. 280:241-244(1991).
RN [14]
RP MUTAGENESIS OF PHE-427.
RX PubMed=1678390; DOI=10.1016/s0021-9258(18)98642-4;
RA Suryanarayana S., Daunt D.A., von Zastrow M., Kobilka B.K.;
RT "A point mutation in the seventh hydrophobic domain of the alpha 2
RT adrenergic receptor increases its affinity for a family of beta receptor
RT antagonists.";
RL J. Biol. Chem. 266:15488-15492(1991).
RN [15]
RP MUTAGENESIS OF ASPARTIC ACID AND SERINE RESIDUES.
RX PubMed=1678850;
RA Wang C.-D., Buck M.A., Fraser C.M.;
RT "Site-directed mutagenesis of alpha 2a-adrenergic receptors: Identification
RT of amino acids involved in ligand binding and receptor activation by
RT agonists.";
RL Mol. Pharmacol. 40:168-179(1991).
RN [16]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23105096; DOI=10.1074/jbc.m112.410936;
RA Li C., Fan Y., Lan T.H., Lambert N.A., Wu G.;
RT "Rab26 modulates the cell surface transport of alpha2-adrenergic receptors
RT from the Golgi.";
RL J. Biol. Chem. 287:42784-42794(2012).
RN [17]
RP STRUCTURE BY NMR OF 133-164, AND PROBABLE MEMBRANE TOPOLOGY.
RX PubMed=11888275; DOI=10.1021/bi015811+;
RA Chung D.A., Zuiderweg E.R.P., Fowler C.B., Soyer O.S., Mosberg H.I.,
RA Neubig R.R.;
RT "NMR structure of the second intracellular loop of the alpha 2A adrenergic
RT receptor: evidence for a novel cytoplasmic helix.";
RL Biochemistry 41:3596-3604(2002).
CC -!- FUNCTION: Alpha-2 adrenergic receptors mediate the catecholamine-
CC induced inhibition of adenylate cyclase through the action of G
CC proteins. The rank order of potency for agonists of this receptor is
CC oxymetazoline > clonidine > epinephrine > norepinephrine >
CC phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-
CC octopamine. For antagonists, the rank order is yohimbine > phentolamine
CC = mianserine > chlorpromazine = spiperone = prazosin > propanolol >
CC alprenolol = pindolol. {ECO:0000269|PubMed:23105096}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23105096};
CC Multi-pass membrane protein {ECO:0000269|PubMed:23105096}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC Adrenergic receptor subfamily. ADRA2A sub-subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-16 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA51664.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAA51664.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAA51665.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAA51665.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAG00447.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH35047.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH50414.4; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAK26743.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAK51162.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAZ73101.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=ABB72683.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=ABY87535.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/adra2a/";
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DR EMBL; M23533; AAA51665.1; ALT_SEQ; Genomic_DNA.
DR EMBL; DQ149926; AAZ73101.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF284095; AAK26743.1; ALT_INIT; mRNA.
DR EMBL; AF262016; AAG00447.2; ALT_INIT; Genomic_DNA.
DR EMBL; AY032736; AAK51162.1; ALT_INIT; Genomic_DNA.
DR EMBL; DQ285607; ABB72683.1; ALT_INIT; Genomic_DNA.
DR EMBL; EU332846; ABY87535.1; ALT_INIT; Genomic_DNA.
DR EMBL; AL158163; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC035047; AAH35047.1; ALT_INIT; mRNA.
DR EMBL; BC050414; AAH50414.4; ALT_INIT; mRNA.
DR EMBL; M18415; AAA51664.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AF281308; AAF91441.1; -; Genomic_DNA.
DR EMBL; AF316894; AAK01634.1; -; Genomic_DNA.
DR CCDS; CCDS7569.2; -.
DR PIR; A34169; A34169.
DR RefSeq; NP_000672.3; NM_000681.3.
DR PDB; 1HLL; NMR; -; A=133-164.
DR PDB; 1HO9; NMR; -; A=133-164.
DR PDB; 1HOD; NMR; -; A=133-164.
DR PDB; 1HOF; NMR; -; A=133-164.
DR PDB; 6K42; EM; 4.10 A; R=37-44.
DR PDB; 6KUX; X-ray; 2.70 A; A=35-460.
DR PDB; 6KUY; X-ray; 3.20 A; A=35-460.
DR PDB; 7EJ0; EM; 3.20 A; R=1-465.
DR PDB; 7EJ8; EM; 3.00 A; R=1-465.
DR PDB; 7EJA; EM; 3.60 A; R=1-465.
DR PDB; 7EJK; EM; 3.40 A; R=1-465.
DR PDBsum; 1HLL; -.
DR PDBsum; 1HO9; -.
DR PDBsum; 1HOD; -.
DR PDBsum; 1HOF; -.
DR PDBsum; 6K42; -.
DR PDBsum; 6KUX; -.
DR PDBsum; 6KUY; -.
DR PDBsum; 7EJ0; -.
DR PDBsum; 7EJ8; -.
DR PDBsum; 7EJA; -.
DR PDBsum; 7EJK; -.
DR AlphaFoldDB; P08913; -.
DR BMRB; P08913; -.
DR SMR; P08913; -.
DR BioGRID; 106659; 9.
DR CORUM; P08913; -.
DR DIP; DIP-61452N; -.
DR IntAct; P08913; 7.
DR STRING; 9606.ENSP00000280155; -.
DR BindingDB; P08913; -.
DR ChEMBL; CHEMBL1867; -.
DR DrugBank; DB01472; 4-Methoxyamphetamine.
DR DrugBank; DB00321; Amitriptyline.
DR DrugBank; DB00543; Amoxapine.
DR DrugBank; DB00182; Amphetamine.
DR DrugBank; DB00714; Apomorphine.
DR DrugBank; DB00964; Apraclonidine.
DR DrugBank; DB09229; Aranidipine.
DR DrugBank; DB01238; Aripiprazole.
DR DrugBank; DB14185; Aripiprazole lauroxil.
DR DrugBank; DB06216; Asenapine.
DR DrugBank; DB00865; Benzphetamine.
DR DrugBank; DB00217; Bethanidine.
DR DrugBank; DB00484; Brimonidine.
DR DrugBank; DB01200; Bromocriptine.
DR DrugBank; DB00248; Cabergoline.
DR DrugBank; DB01136; Carvedilol.
DR DrugBank; DB04846; Celiprolol.
DR DrugBank; DB00477; Chlorpromazine.
DR DrugBank; DB09202; Cirazoline.
DR DrugBank; DB00575; Clonidine.
DR DrugBank; DB00363; Clozapine.
DR DrugBank; DB01151; Desipramine.
DR DrugBank; DB00633; Dexmedetomidine.
DR DrugBank; DB01576; Dextroamphetamine.
DR DrugBank; DB11273; Dihydroergocornine.
DR DrugBank; DB13345; Dihydroergocristine.
DR DrugBank; DB00320; Dihydroergotamine.
DR DrugBank; DB00449; Dipivefrin.
DR DrugBank; DB11278; DL-Methylephedrine.
DR DrugBank; DB09167; Dosulepin.
DR DrugBank; DB04855; Dronedarone.
DR DrugBank; DB06262; Droxidopa.
DR DrugBank; DB01363; Ephedra sinica root.
DR DrugBank; DB05492; Epicept NP-1.
DR DrugBank; DB00751; Epinastine.
DR DrugBank; DB00668; Epinephrine.
DR DrugBank; DB01049; Ergoloid mesylate.
DR DrugBank; DB00696; Ergotamine.
DR DrugBank; DB01175; Escitalopram.
DR DrugBank; DB06678; Esmirtazapine.
DR DrugBank; DB09194; Etoperidone.
DR DrugBank; DB00800; Fenoldopam.
DR DrugBank; DB06623; Flupirtine.
DR DrugBank; DB00629; Guanabenz.
DR DrugBank; DB01018; Guanfacine.
DR DrugBank; DB00502; Haloperidol.
DR DrugBank; DB11577; Indigotindisulfonic acid.
DR DrugBank; DB00555; Lamotrigine.
DR DrugBank; DB06707; Levonordefrin.
DR DrugBank; DB00589; Lisuride.
DR DrugBank; DB04948; Lofexidine.
DR DrugBank; DB09195; Lorpiprazole.
DR DrugBank; DB00408; Loxapine.
DR DrugBank; DB08815; Lurasidone.
DR DrugBank; DB00934; Maprotiline.
DR DrugBank; DB01365; Mephentermine.
DR DrugBank; DB01577; Metamfetamine.
DR DrugBank; DB01403; Methotrimeprazine.
DR DrugBank; DB00968; Methyldopa.
DR DrugBank; DB06148; Mianserin.
DR DrugBank; DB00370; Mirtazapine.
DR DrugBank; DB09205; Moxisylyte.
DR DrugBank; DB09242; Moxonidine.
DR DrugBank; DB06711; Naphazoline.
DR DrugBank; DB01149; Nefazodone.
DR DrugBank; DB00368; Norepinephrine.
DR DrugBank; DB00540; Nortriptyline.
DR DrugBank; DB06229; Ocaperidone.
DR DrugBank; DB00935; Oxymetazoline.
DR DrugBank; DB01267; Paliperidone.
DR DrugBank; DB00715; Paroxetine.
DR DrugBank; DB01186; Pergolide.
DR DrugBank; DB01608; Periciazine.
DR DrugBank; DB00925; Phenoxybenzamine.
DR DrugBank; DB00692; Phentolamine.
DR DrugBank; DB00397; Phenylpropanolamine.
DR DrugBank; DB09286; Pipamperone.
DR DrugBank; DB09244; Pirlindole.
DR DrugBank; DB06153; Pizotifen.
DR DrugBank; DB00413; Pramipexole.
DR DrugBank; DB00457; Prazosin.
DR DrugBank; DB00433; Prochlorperazine.
DR DrugBank; DB01069; Promethazine.
DR DrugBank; DB00852; Pseudoephedrine.
DR DrugBank; DB01224; Quetiapine.
DR DrugBank; DB11124; Racepinephrine.
DR DrugBank; DB11738; Rilmenidine.
DR DrugBank; DB00268; Ropinirole.
DR DrugBank; DB09304; Setiptiline.
DR DrugBank; DB06764; Tetryzoline.
DR DrugBank; DB13025; Tiapride.
DR DrugBank; DB00697; Tizanidine.
DR DrugBank; DB00797; Tolazoline.
DR DrugBank; DB00193; Tramadol.
DR DrugBank; DB00656; Trazodone.
DR DrugBank; DB00726; Trimipramine.
DR DrugBank; DB11477; Xylazine.
DR DrugBank; DB06694; Xylometazoline.
DR DrugBank; DB01392; Yohimbine.
DR DrugBank; DB00246; Ziprasidone.
DR DrugBank; DB01624; Zuclopenthixol.
DR DrugCentral; P08913; -.
DR GuidetoPHARMACOLOGY; 25; -.
DR TCDB; 9.A.14.3.16; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; P08913; 2 sites.
DR iPTMnet; P08913; -.
DR PhosphoSitePlus; P08913; -.
DR BioMuta; ADRA2A; -.
DR DMDM; 1351829; -.
DR jPOST; P08913; -.
DR MassIVE; P08913; -.
DR PaxDb; P08913; -.
DR PeptideAtlas; P08913; -.
DR PRIDE; P08913; -.
DR ProteomicsDB; 52176; -.
DR Antibodypedia; 31769; 349 antibodies from 37 providers.
DR DNASU; 150; -.
DR Ensembl; ENST00000280155.4; ENSP00000280155.2; ENSG00000150594.7.
DR GeneID; 150; -.
DR KEGG; hsa:150; -.
DR MANE-Select; ENST00000280155.4; ENSP00000280155.2; NM_000681.4; NP_000672.3.
DR UCSC; uc001kzo.4; human.
DR CTD; 150; -.
DR DisGeNET; 150; -.
DR GeneCards; ADRA2A; -.
DR HGNC; HGNC:281; ADRA2A.
DR HPA; ENSG00000150594; Tissue enhanced (adipose tissue, cervix).
DR MIM; 104210; gene.
DR neXtProt; NX_P08913; -.
DR OpenTargets; ENSG00000150594; -.
DR PharmGKB; PA35; -.
DR VEuPathDB; HostDB:ENSG00000150594; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000161451; -.
DR HOGENOM; CLU_009579_11_1_1; -.
DR InParanoid; P08913; -.
DR OMA; KILCRVD; -.
DR OrthoDB; 737211at2759; -.
DR PhylomeDB; P08913; -.
DR TreeFam; TF316350; -.
DR PathwayCommons; P08913; -.
DR Reactome; R-HSA-390696; Adrenoceptors.
DR Reactome; R-HSA-392023; Adrenaline signalling through Alpha-2 adrenergic receptor.
DR Reactome; R-HSA-400042; Adrenaline,noradrenaline inhibits insulin secretion.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-418597; G alpha (z) signalling events.
DR Reactome; R-HSA-5683826; Surfactant metabolism.
DR SignaLink; P08913; -.
DR SIGNOR; P08913; -.
DR BioGRID-ORCS; 150; 9 hits in 1068 CRISPR screens.
DR ChiTaRS; ADRA2A; human.
DR EvolutionaryTrace; P08913; -.
DR GeneWiki; Alpha-2A_adrenergic_receptor; -.
DR GenomeRNAi; 150; -.
DR Pharos; P08913; Tclin.
DR PRO; PR:P08913; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P08913; protein.
DR Bgee; ENSG00000150594; Expressed in cortical plate and 157 other tissues.
DR Genevisible; P08913; HS.
DR GO; GO:0043679; C:axon terminus; IEA:Ensembl.
DR GO; GO:0016323; C:basolateral plasma membrane; TAS:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0098691; C:dopaminergic synapse; IEA:Ensembl.
DR GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; IEA:Ensembl.
DR GO; GO:0099059; C:integral component of presynaptic active zone membrane; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043235; C:receptor complex; IDA:BHF-UCL.
DR GO; GO:0031692; F:alpha-1B adrenergic receptor binding; ISS:BHF-UCL.
DR GO; GO:0031696; F:alpha-2C adrenergic receptor binding; IPI:BHF-UCL.
DR GO; GO:0004938; F:alpha2-adrenergic receptor activity; IDA:BHF-UCL.
DR GO; GO:0051379; F:epinephrine binding; IDA:BHF-UCL.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0032795; F:heterotrimeric G-protein binding; IDA:BHF-UCL.
DR GO; GO:0051380; F:norepinephrine binding; IDA:BHF-UCL.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL.
DR GO; GO:0031996; F:thioesterase binding; IPI:BHF-UCL.
DR GO; GO:0030036; P:actin cytoskeleton organization; TAS:ProtInc.
DR GO; GO:0032147; P:activation of protein kinase activity; IDA:BHF-UCL.
DR GO; GO:0032148; P:activation of protein kinase B activity; IDA:BHF-UCL.
DR GO; GO:0002526; P:acute inflammatory response; IEA:Ensembl.
DR GO; GO:0071880; P:adenylate cyclase-activating adrenergic receptor signaling pathway; ISS:BHF-UCL.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISS:BHF-UCL.
DR GO; GO:0071881; P:adenylate cyclase-inhibiting adrenergic receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; ISS:BHF-UCL.
DR GO; GO:0071875; P:adrenergic receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0032870; P:cellular response to hormone stimulus; IGI:BHF-UCL.
DR GO; GO:0006260; P:DNA replication; IEA:Ensembl.
DR GO; GO:0042596; P:fear response; IEA:Ensembl.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0042593; P:glucose homeostasis; IMP:BHF-UCL.
DR GO; GO:0050892; P:intestinal absorption; TAS:BHF-UCL.
DR GO; GO:1901020; P:negative regulation of calcium ion transmembrane transporter activity; ISS:BHF-UCL.
DR GO; GO:0051926; P:negative regulation of calcium ion transport; ISS:BHF-UCL.
DR GO; GO:0045955; P:negative regulation of calcium ion-dependent exocytosis; IC:BHF-UCL.
DR GO; GO:0032811; P:negative regulation of epinephrine secretion; NAS:BHF-UCL.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IMP:BHF-UCL.
DR GO; GO:0061179; P:negative regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:BHF-UCL.
DR GO; GO:0050995; P:negative regulation of lipid catabolic process; IGI:BHF-UCL.
DR GO; GO:0010700; P:negative regulation of norepinephrine secretion; TAS:BHF-UCL.
DR GO; GO:0070473; P:negative regulation of uterine smooth muscle contraction; IEA:Ensembl.
DR GO; GO:0071882; P:phospholipase C-activating adrenergic receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0030168; P:platelet activation; IEA:InterPro.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; TAS:ProtInc.
DR GO; GO:0001819; P:positive regulation of cytokine production; IDA:BHF-UCL.
DR GO; GO:0045741; P:positive regulation of epidermal growth factor-activated receptor activity; IDA:BHF-UCL.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:BHF-UCL.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:BHF-UCL.
DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IDA:BHF-UCL.
DR GO; GO:0043268; P:positive regulation of potassium ion transport; ISS:BHF-UCL.
DR GO; GO:0090303; P:positive regulation of wound healing; IMP:BHF-UCL.
DR GO; GO:0007265; P:Ras protein signal transduction; TAS:ProtInc.
DR GO; GO:0035624; P:receptor transactivation; IDA:BHF-UCL.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IEA:Ensembl.
DR GO; GO:0019229; P:regulation of vasoconstriction; IEA:InterPro.
DR GO; GO:0007266; P:Rho protein signal transduction; TAS:ProtInc.
DR GO; GO:0050955; P:thermoception; IEA:Ensembl.
DR GO; GO:0042311; P:vasodilation; IEA:Ensembl.
DR InterPro; IPR002233; ADR_fam.
DR InterPro; IPR001946; ADRA2A_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR01103; ADRENERGICR.
DR PRINTS; PR00558; ADRENRGCA2AR.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR SMART; SM01381; 7TM_GPCR_Srsx; 1.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Direct protein sequencing; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane;
KW Methylation; Palmitate; Phosphoprotein; Receptor; Reference proteome;
KW Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..465
FT /note="Alpha-2A adrenergic receptor"
FT /id="PRO_0000069080"
FT TOPO_DOM 1..48
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 49..74
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 75..85
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 86..111
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 112..121
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 122..144
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250"
FT TOPO_DOM 145..166
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 167..187
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250"
FT TOPO_DOM 188..209
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 210..232
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250"
FT TOPO_DOM 233..389
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 390..410
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250"
FT TOPO_DOM 411..424
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 425..444
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250"
FT TOPO_DOM 445..465
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 242..368
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 303..334
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 128
FT /note="Implicated in ligand binding"
FT SITE 215
FT /note="Implicated in catechol agonist binding and receptor
FT activation"
FT SITE 219
FT /note="Implicated in catechol agonist binding and receptor
FT activation"
FT MOD_RES 346
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22909"
FT MOD_RES 368
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q01338"
FT LIPID 457
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 25
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 29
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 121..203
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VARIANT 266
FT /note="N -> K (frequency in Caucasians 0.004 and in
FT African-Americans 0.05; 40% increase in agonist-promoted Gi
FT coupling; dbSNP:rs1800035)"
FT /evidence="ECO:0000269|PubMed:10948191, ECO:0000269|Ref.7"
FT /id="VAR_014957"
FT VARIANT 416
FT /note="C -> S (in dbSNP:rs35658213)"
FT /id="VAR_055908"
FT MUTAGEN 94
FT /note="D->N: No change in binding affinity. eliminates
FT guanine nucleotide-sensitive agonist binding."
FT /evidence="ECO:0000269|PubMed:1678850"
FT MUTAGEN 128
FT /note="D->N: No binding to yohimbine. Increase in adenylate
FT cyclase activity."
FT /evidence="ECO:0000269|PubMed:1678850"
FT MUTAGEN 145
FT /note="D->N: Lower affinity for agonists. Eliminates
FT guanine nucleotide-sensitive agonist binding."
FT /evidence="ECO:0000269|PubMed:1678850"
FT MUTAGEN 215
FT /note="S->A: Lower affinity for agonists. No change in
FT guanine nucleotide-sensitive agonist binding."
FT /evidence="ECO:0000269|PubMed:1678850"
FT MUTAGEN 219
FT /note="S->A: Lower affinity for agonists. Reduced guanine
FT nucleotide-sensitive agonist binding."
FT /evidence="ECO:0000269|PubMed:1678850"
FT MUTAGEN 427
FT /note="F->N: 350-fold reduced affinity for alpha-2
FT antagonist yohimbine, 3000-fold increase for beta-
FT antagonist alprenolol."
FT /evidence="ECO:0000269|PubMed:1678390"
FT CONFLICT 119
FT /note="A -> T (in Ref. 11; AAA51664)"
FT /evidence="ECO:0000305"
FT CONFLICT 139
FT /note="L -> P (in Ref. 13)"
FT /evidence="ECO:0000305"
FT CONFLICT 172
FT /note="V -> C (in Ref. 11; AAA51664)"
FT /evidence="ECO:0000305"
FT CONFLICT 383
FT /note="R -> L (in Ref. 11; AAA51664)"
FT /evidence="ECO:0000305"
FT HELIX 49..75
FT /evidence="ECO:0007829|PDB:6KUX"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:6KUX"
FT HELIX 82..84
FT /evidence="ECO:0007829|PDB:6KUX"
FT HELIX 85..99
FT /evidence="ECO:0007829|PDB:6KUX"
FT HELIX 102..110
FT /evidence="ECO:0007829|PDB:6KUX"
FT HELIX 118..151
FT /evidence="ECO:0007829|PDB:6KUX"
FT HELIX 153..158
FT /evidence="ECO:0007829|PDB:6KUX"
FT HELIX 162..180
FT /evidence="ECO:0007829|PDB:6KUX"
FT TURN 209..211
FT /evidence="ECO:0007829|PDB:6KUX"
FT HELIX 212..219
FT /evidence="ECO:0007829|PDB:6KUX"
FT HELIX 221..242
FT /evidence="ECO:0007829|PDB:6KUX"
FT HELIX 255..272
FT /evidence="ECO:0007829|PDB:6KUX"
FT HELIX 278..296
FT /evidence="ECO:0007829|PDB:6KUX"
FT TURN 308..310
FT /evidence="ECO:0007829|PDB:6KUX"
FT HELIX 326..341
FT /evidence="ECO:0007829|PDB:6KUX"
FT HELIX 344..350
FT /evidence="ECO:0007829|PDB:6KUX"
FT TURN 351..353
FT /evidence="ECO:0007829|PDB:6KUX"
FT HELIX 355..362
FT /evidence="ECO:0007829|PDB:6KUX"
FT HELIX 367..377
FT /evidence="ECO:0007829|PDB:6KUX"
FT HELIX 383..411
FT /evidence="ECO:0007829|PDB:6KUX"
FT HELIX 412..414
FT /evidence="ECO:0007829|PDB:6KUX"
FT HELIX 420..431
FT /evidence="ECO:0007829|PDB:6KUX"
FT HELIX 433..444
FT /evidence="ECO:0007829|PDB:6KUX"
FT HELIX 446..457
FT /evidence="ECO:0007829|PDB:6KUX"
SQ SEQUENCE 465 AA; 50647 MW; 585E576149BDB696 CRC64;
MFRQEQPLAE GSFAPMGSLQ PDAGNASWNG TEAPGGGARA TPYSLQVTLT LVCLAGLLML
LTVFGNVLVI IAVFTSRALK APQNLFLVSL ASADILVATL VIPFSLANEV MGYWYFGKAW
CEIYLALDVL FCTSSIVHLC AISLDRYWSI TQAIEYNLKR TPRRIKAIII TVWVISAVIS
FPPLISIEKK GGGGGPQPAE PRCEINDQKW YVISSCIGSF FAPCLIMILV YVRIYQIAKR
RTRVPPSRRG PDAVAAPPGG TERRPNGLGP ERSAGPGGAE AEPLPTQLNG APGEPAPAGP
RDTDALDLEE SSSSDHAERP PGPRRPERGP RGKGKARASQ VKPGDSLPRR GPGATGIGTP
AAGPGEERVG AAKASRWRGR QNREKRFTFV LAVVIGVFVV CWFPFFFTYT LTAVGCSVPR
TLFKFFFWFG YCNSSLNPVI YTIFNHDFRR AFKKILCRGD RKRIV
