ID   ADA2A_MOUSE             Reviewed;         465 AA.
AC   Q01338; Q3URE6;
DT   01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT   11-DEC-2019, sequence version 2.
DT   27-MAR-2024, entry version 179.
DE   RecName: Full=Alpha-2A adrenergic receptor {ECO:0000305};
DE   AltName: Full=Alpha-2A adrenoreceptor;
DE            Short=Alpha-2A adrenoceptor;
DE            Short=Alpha-2AAR;
GN   Name=Adra2a {ECO:0000312|MGI:MGI:87934};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1353249;
RA   Link R.E., Daunt D.A., Barsh G., Chruscinski A.J., Kobilka B.K.;
RT   "Cloning of two mouse genes encoding alpha 2-adrenergic receptor subtypes
RT   and identification of a single amino acid in the mouse alpha 2-C10 homolog
RT   responsible for an interspecies variation in antagonist binding.";
RL   Mol. Pharmacol. 42:16-27(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Hippocampus;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [6]
RP   METHYLATION [LARGE SCALE ANALYSIS] AT ARG-368, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain;
RX   PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA   Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA   Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA   Bedford M.T., Comb M.J.;
RT   "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT   methylation.";
RL   Mol. Cell. Proteomics 13:372-387(2014).
CC   -!- FUNCTION: Alpha-2 adrenergic receptors mediate the catecholamine-
CC       induced inhibition of adenylate cyclase through the action of G
CC       proteins.
CC   -!- INTERACTION:
CC       Q01338; Q14232: EIF2B1; Xeno; NbExp=2; IntAct=EBI-491073, EBI-491065;
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
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=AAA37213.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAA37213.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; M99377; AAA37213.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; AK141573; BAE24742.1; -; mRNA.
DR   EMBL; AC113491; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC138531; AAI38532.1; -; mRNA.
DR   CCDS; CCDS29905.1; -.
DR   PIR; I49481; I49481.
DR   RefSeq; NP_031443.4; NM_007417.4.
DR   AlphaFoldDB; Q01338; -.
DR   BMRB; Q01338; -.
DR   SMR; Q01338; -.
DR   IntAct; Q01338; 1.
DR   STRING; 10090.ENSMUSP00000036203; -.
DR   ChEMBL; CHEMBL4075; -.
DR   DrugCentral; Q01338; -.
DR   GlyCosmos; Q01338; 2 sites, No reported glycans.
DR   GlyGen; Q01338; 2 sites.
DR   iPTMnet; Q01338; -.
DR   PhosphoSitePlus; Q01338; -.
DR   MaxQB; Q01338; -.
DR   PaxDb; 10090-ENSMUSP00000036203; -.
DR   PeptideAtlas; Q01338; -.
DR   ProteomicsDB; 285608; -.
DR   ProteomicsDB; 344753; -.
DR   Antibodypedia; 31769; 375 antibodies from 37 providers.
DR   DNASU; 11551; -.
DR   Ensembl; ENSMUST00000036700.7; ENSMUSP00000036203.6; ENSMUSG00000033717.7.
DR   Ensembl; ENSMUST00000237285.2; ENSMUSP00000157421.2; ENSMUSG00000033717.7.
DR   GeneID; 11551; -.
DR   KEGG; mmu:11551; -.
DR   UCSC; uc008hxi.1; mouse.
DR   AGR; MGI:87934; -.
DR   CTD; 150; -.
DR   MGI; MGI:87934; Adra2a.
DR   VEuPathDB; HostDB:ENSMUSG00000033717; -.
DR   eggNOG; KOG3656; Eukaryota.
DR   GeneTree; ENSGT00940000161451; -.
DR   HOGENOM; CLU_009579_11_1_1; -.
DR   InParanoid; Q01338; -.
DR   OMA; FFTYMLM; -.
DR   OrthoDB; 3087922at2759; -.
DR   PhylomeDB; Q01338; -.
DR   TreeFam; TF316350; -.
DR   Reactome; R-MMU-390696; Adrenoceptors.
DR   Reactome; R-MMU-392023; Adrenaline signalling through Alpha-2 adrenergic receptor.
DR   Reactome; R-MMU-400042; Adrenaline,noradrenaline inhibits insulin secretion.
DR   Reactome; R-MMU-418594; G alpha (i) signalling events.
DR   Reactome; R-MMU-418597; G alpha (z) signalling events.
DR   Reactome; R-MMU-5683826; Surfactant metabolism.
DR   BioGRID-ORCS; 11551; 4 hits in 79 CRISPR screens.
DR   PRO; PR:Q01338; -.
DR   Proteomes; UP000000589; Chromosome 19.
DR   RNAct; Q01338; Protein.
DR   Bgee; ENSMUSG00000033717; Expressed in pontine nuclear group and 170 other cell types or tissues.
DR   GO; GO:0043679; C:axon terminus; ISO:MGI.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0098691; C:dopaminergic synapse; IDA:SynGO.
DR   GO; GO:0098982; C:GABA-ergic synapse; ISO:MGI.
DR   GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR   GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0098839; C:postsynaptic density membrane; ISO:MGI.
DR   GO; GO:0045211; C:postsynaptic membrane; ISO:MGI.
DR   GO; GO:0048787; C:presynaptic active zone membrane; ISO:MGI.
DR   GO; GO:0043235; C:receptor complex; ISO:MGI.
DR   GO; GO:0004935; F:adrenergic receptor activity; IMP:MGI.
DR   GO; GO:0031696; F:alpha-2C adrenergic receptor binding; ISO:MGI.
DR   GO; GO:0004938; F:alpha2-adrenergic receptor activity; IMP:MGI.
DR   GO; GO:0051379; F:epinephrine binding; ISO:MGI.
DR   GO; GO:0032795; F:heterotrimeric G-protein binding; ISO:MGI.
DR   GO; GO:0051380; F:norepinephrine binding; ISO:MGI.
DR   GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR   GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR   GO; GO:0031996; F:thioesterase binding; ISO:MGI.
DR   GO; GO:0071880; P:adenylate cyclase-activating adrenergic receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0071881; P:adenylate cyclase-inhibiting adrenergic receptor signaling pathway; ISO:MGI.
DR   GO; GO:0071875; P:adrenergic receptor signaling pathway; ISO:MGI.
DR   GO; GO:0032870; P:cellular response to hormone stimulus; ISO:MGI.
DR   GO; GO:0006260; P:DNA replication; ISO:MGI.
DR   GO; GO:0042596; P:fear response; IMP:MGI.
DR   GO; GO:0007565; P:female pregnancy; ISO:MGI.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:MGI.
DR   GO; GO:0042593; P:glucose homeostasis; ISO:MGI.
DR   GO; GO:0045955; P:negative regulation of calcium ion-dependent exocytosis; ISO:MGI.
DR   GO; GO:0046676; P:negative regulation of insulin secretion; IDA:MGI.
DR   GO; GO:0061179; P:negative regulation of insulin secretion involved in cellular response to glucose stimulus; ISO:MGI.
DR   GO; GO:0050995; P:negative regulation of lipid catabolic process; ISO:MGI.
DR   GO; GO:0070473; P:negative regulation of uterine smooth muscle contraction; ISO:MGI.
DR   GO; GO:0071882; P:phospholipase C-activating adrenergic receptor signaling pathway; ISO:MGI.
DR   GO; GO:0030168; P:platelet activation; IEA:InterPro.
DR   GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR   GO; GO:0001819; P:positive regulation of cytokine production; ISO:MGI.
DR   GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; ISO:MGI.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:MGI.
DR   GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; ISO:MGI.
DR   GO; GO:0090303; P:positive regulation of wound healing; ISO:MGI.
DR   GO; GO:0099171; P:presynaptic modulation of chemical synaptic transmission; IDA:SynGO.
DR   GO; GO:0019229; P:regulation of vasoconstriction; IEA:InterPro.
DR   GO; GO:0050955; P:thermoception; ISO:MGI.
DR   GO; GO:0042311; P:vasodilation; ISO:MGI.
DR   CDD; cd15322; 7tmA_alpha2A_AR; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR   InterPro; IPR002233; ADR_fam.
DR   InterPro; IPR001946; ADRA2A_rcpt.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   PANTHER; PTHR24248; ADRENERGIC RECEPTOR-RELATED G-PROTEIN COUPLED RECEPTOR; 1.
DR   PANTHER; PTHR24248:SF24; ALPHA-2A ADRENERGIC RECEPTOR; 1.
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   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 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   Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW   Lipoprotein; Membrane; Methylation; Palmitate; Phosphoprotein; Receptor;
KW   Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT   CHAIN           1..465
FT                   /note="Alpha-2A adrenergic receptor"
FT                   /id="PRO_0000069081"
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..164
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        165..188
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        189..207
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        208..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..414
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        415..424
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        425..445
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        446..465
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   REGION          242..378
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                   /evidence="ECO:0000250"
FT   SITE            215
FT                   /note="Implicated in catechol agonist binding"
FT                   /evidence="ECO:0000250"
FT   SITE            219
FT                   /note="Implicated in catechol agonist binding"
FT                   /evidence="ECO:0000250"
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:0007744|PubMed:24129315"
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"
SQ   SEQUENCE   465 AA;  50555 MW;  0F23BA14F516F701 CRC64;
     MFRQEQPLAE GSFAPMGSLQ PDAGNSSWNG TEAPGGGTRA TPYSLQVTLT LVCLAGLLML
     FTVFGNVLVI IAVFTSRALK APQNLFLVSL ASADILVATL VIPFSLANEV MGYWYFGKVW
     CEIYLALDVL FCTSSIVHLC AISLDRYWSI TQAIEYNLKR TPRRIKAIIV TVWVISAVIS
     FPPLISIEKK GAGGGQQPAE PSCKINDQKW YVISSSIGSF FAPCLIMILV YVRIYQIAKR
     RTRVPPSRRG PDACSAPPGG ADRRPNGLGP ERGAGPTGAE AEPLPTQLNG APGEPAPAGP
     RDGDALDLEE SSSSEHAERP PGPRRPDRGP RAKGKTRASQ VKPGDSLPRR GPGAAGPGAS
     GSGHGEERGG GAKASRWRGR QNREKRFTFV LAVVIGVFVV CWFPFFFTYT LIAVGCPVPS
     QLFNFFFWFG YCNSSLNPVI YTIFNHDFRR AFKKILCRGD RKRIV
//