ID ADA1A_MOUSE Reviewed; 466 AA. AC P97718; O54913; Q8BV77; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 3. DT 02-SEP-2026, entry version 196. DE RecName: Full=Alpha-1A adrenergic receptor {ECO:0000250|UniProtKB:P35348}; DE AltName: Full=Alpha-1A adrenoreceptor; DE Short=Alpha-1A adrenoceptor {ECO:0000250|UniProtKB:Q9WU25}; DE AltName: Full=Alpha-1C adrenergic receptor {ECO:0000250|UniProtKB:P35348}; GN Name=Adra1a {ECO:0000312|MGI:MGI:104773}; Synonyms=Adra1c; 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 [MRNA], AND CHARACTERIZATION. RC STRAIN=CD-1; TISSUE=Brain, and Kidney; RX PubMed=9630362; DOI=10.1038/sj.bjp.0701812; RA Xiao L., Scofield M.A., Jeffries W.B.; RT "Molecular cloning, expression and characterization of cDNA encoding a RT mouse alpha1a-adrenoceptor."; RL Br. J. Pharmacol. 124:213-221(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Spinal cord; 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]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 NUCLEOTIDE SEQUENCE [MRNA] OF 197-280. RC TISSUE=Brain; RX PubMed=7595531; DOI=10.1046/j.1471-4159.1995.65062387.x; RA Alonso-Llamazares A., Zamanillo D., Casanova E., Ovalle S., Calvo P., RA Chinchetru M.A.; RT "Molecular cloning of alpha 1d-adrenergic receptor and tissue distribution RT of three alpha 1-adrenergic receptor subtypes in mouse."; RL J. Neurochem. 65:2387-2392(1995). RN [6] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=12093905; DOI=10.1073/pnas.132552699; RA Rokosh D.G., Simpson P.C.; RT "Knockout of the alpha 1A/C-adrenergic receptor subtype: the alpha 1A/C is RT expressed in resistance arteries and is required to maintain arterial blood RT pressure."; RL Proc. Natl. Acad. Sci. U.S.A. 99:9474-9479(2002). RN [7] RP SUBCELLULAR LOCATION. RX PubMed=22120526; DOI=10.1016/j.cellsig.2011.11.014; RA Wright C.D., Wu S.C., Dahl E.F., Sazama A.J., O'Connell T.D.; RT "Nuclear localization drives alpha1-adrenergic receptor oligomerization and RT signaling in cardiac myocytes."; RL Cell. Signal. 24:794-802(2012). CC -!- FUNCTION: Alpha-1 adrenergic receptors are G protein-coupled receptors CC for catecholamines that signal through the G(q) family of G proteins, CC including G(q) and G(11). Upon activation, they stimulate the CC phosphatidylinositol-calcium second messenger pathway, leading to CC calcium release from intracellular stores and activation of protein CC kinase C. ADRA1A binds the catecholamine ligands norepinephrine and CC epinephrine (By similarity). Can also couple to G(14) protein (By CC similarity). Nuclear ADRA1A forms heterooligomers with ADRA1B to CC regulate phenylephrine(PE)-stimulated ERK signaling in cardiac CC myocytes. At the plasma membrane, ADRA1A interacts with CAVIN4/MURC to CC regulates ERK activation in cardiomyocytes, contributing to the CC regulation of cardiac hypertrophy (By similarity). Additionally, CC functions as a vasopressor in resistance arteries and plays a role in CC maintaining normal arterial blood pressure (PubMed:12093905). CC {ECO:0000250|UniProtKB:P18130, ECO:0000250|UniProtKB:P35348, CC ECO:0000269|PubMed:12093905}. CC -!- SUBUNIT: Homo- and heterooligomer. Heterooligomerizes with ADRA1B CC homooligomers in cardiac myocytes. Interacts with CAVIN4. CC {ECO:0000250|UniProtKB:P35348}. CC -!- SUBCELLULAR LOCATION: Nucleus membrane {ECO:0000250|UniProtKB:P35348}; CC Multi-pass membrane protein. Cell membrane CC {ECO:0000250|UniProtKB:P35348}; Multi-pass membrane protein CC {ECO:0000255}. Cytoplasm {ECO:0000250|UniProtKB:P35348}. Membrane, CC caveola {ECO:0000250|UniProtKB:P35348}. Note=Location at the nuclear CC membrane facilitates heterooligomerization and regulates ERK-mediated CC signaling in cardiac myocytes. Colocalizes with GNAQ, PLCB1 as well as CC LAP2 at the nuclear membrane of cardiac myocytes. Colocalizes with CC CAVIN4 and CAV3 at the plasma membrane and partly within the cytoplasm CC in cardiomyocytes. {ECO:0000250|UniProtKB:P35348}. CC -!- DISRUPTION PHENOTYPE: Knockout mice are viable and overtly normal CC (PubMed:12093905). Knockout mice are hypotensive at rest following CC ADRA1A receptor activation (PubMed:12093905). CC {ECO:0000269|PubMed:12093905}. CC -!- SIMILARITY: Belongs to the G protein-coupled receptor 1 family. CC Adrenergic receptor subfamily. ADRA1A sub-subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB47044.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF031431; AAC02658.1; -; mRNA. DR EMBL; AK079597; BAC37694.1; -; mRNA. DR EMBL; CH466535; EDL35992.1; -; Genomic_DNA. DR EMBL; BC113139; AAI13140.1; -; mRNA. DR EMBL; S80220; AAB47044.1; ALT_INIT; mRNA. DR CCDS; CCDS27223.1; -. DR RefSeq; NP_001258689.1; NM_001271760.2. DR RefSeq; NP_001409021.1; NM_001422092.1. DR RefSeq; NP_001409022.1; NM_001422093.1. DR RefSeq; NP_001409024.1; NM_001422095.1. DR RefSeq; NP_001409025.1; NM_001422096.1. DR RefSeq; NP_038489.2; NM_013461.5. DR RefSeq; XP_011243225.1; XM_011244923.4. DR RefSeq; XP_011243226.1; XM_011244924.4. DR RefSeq; XP_011243227.1; XM_011244925.4. DR AlphaFoldDB; P97718; -. DR SMR; P97718; -. DR CORUM; P97718; -. DR FunCoup; P97718; 1163. DR IntAct; P97718; 1. DR STRING; 10090.ENSMUSP00000124570; -. DR BindingDB; P97718; -. DR ChEMBL; CHEMBL2822; -. DR GlyCosmos; P97718; 3 sites, No reported glycans. DR GlyGen; P97718; 3 sites. DR iPTMnet; P97718; -. DR PhosphoSitePlus; P97718; -. DR PaxDb; 10090-ENSMUSP00000124570; -. DR ProteomicsDB; 285607; -. DR Antibodypedia; 10062; 384 antibodies from 41 providers. DR DNASU; 11549; -. DR Ensembl; ENSMUST00000054661.8; ENSMUSP00000053703.2; ENSMUSG00000045875.14. DR Ensembl; ENSMUST00000159068.2; ENSMUSP00000124570.2; ENSMUSG00000045875.14. DR Ensembl; ENSMUST00000161339.2; ENSMUSP00000125354.2; ENSMUSG00000045875.14. DR GeneID; 11549; -. DR KEGG; mmu:11549; -. DR UCSC; uc007ukh.2; mouse. DR AGR; MGI:104773; -. DR CTD; 148; -. DR MGI; MGI:104773; Adra1a. DR VEuPathDB; HostDB:ENSMUSG00000045875; -. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT00940000159105; -. DR InParanoid; P97718; -. DR OMA; CLLRKQP; -. DR OrthoDB; 6358729at2759; -. DR PhylomeDB; P97718; -. DR Reactome; R-MMU-390696; Adrenoceptors. DR Reactome; R-MMU-416476; G alpha (q) signalling events. DR Reactome; R-MMU-416482; G alpha (12/13) signalling events. DR BioGRID-ORCS; 11549; 5 hits in 79 CRISPR screens. DR PRO; PR:P97718; -. DR Proteomes; UP000000589; Chromosome 14. DR RNAct; P97718; protein. DR Bgee; ENSMUSG00000045875; Expressed in right kidney and 40 other cell types or tissues. DR ExpressionAtlas; P97718; baseline and differential. DR GO; GO:0005901; C:caveola; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; ISO:GO_Central. DR GO; GO:0098691; C:dopaminergic synapse; ISO:GO_Central. DR GO; GO:0098982; C:GABA-ergic synapse; ISO:GO_Central. DR GO; GO:0098978; C:glutamatergic synapse; ISO:GO_Central. DR GO; GO:0016020; C:membrane; IDA:MGI. DR GO; GO:0031965; C:nuclear membrane; ISS:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; ISO:GO_Central. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0045211; C:postsynaptic membrane; ISO:GO_Central. DR GO; GO:0042734; C:presynaptic membrane; ISO:GO_Central. DR GO; GO:0030315; C:T-tubule; ISO:GO_Central. DR GO; GO:0030018; C:Z disc; ISO:GO_Central. DR GO; GO:0004937; F:alpha1-adrenergic receptor activity; IDA:MGI. DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB. DR GO; GO:0071880; P:adenylate cyclase-activating adrenergic receptor signaling pathway; IBA:GO_Central. DR GO; GO:0071875; P:adrenergic receptor signaling pathway; IDA:MGI. DR GO; GO:0007512; P:adult heart development; IGI:MGI. DR GO; GO:0061049; P:cell growth involved in cardiac muscle cell development; IGI:MGI. DR GO; GO:0007267; P:cell-cell signaling; IBA:GO_Central. DR GO; GO:0010507; P:negative regulation of autophagy; IDA:MGI. DR GO; GO:0001985; P:negative regulation of heart rate involved in baroreceptor response to increased systemic arterial blood pressure; IMP:MGI. DR GO; GO:0035024; P:negative regulation of Rho protein signal transduction; ISO:MGI. DR GO; GO:0150099; P:neuron-glial cell signaling; IGI:ARUK-UCL. DR GO; GO:0001994; P:norepinephrine-epinephrine vasoconstriction involved in regulation of systemic arterial blood pressure; IMP:UniProtKB. DR GO; GO:0035265; P:organ growth; IGI:MGI. DR GO; GO:0071882; P:phospholipase C-activating adrenergic receptor signaling pathway; ISO:GO_Central. DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IDA:MGI. DR GO; GO:0097195; P:pilomotor reflex; IDA:BHF-UCL. DR GO; GO:0045760; P:positive regulation of action potential; ISO:GO_Central. DR GO; GO:0060452; P:positive regulation of cardiac muscle contraction; ISO:GO_Central. DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IDA:MGI. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:GO_Central. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:GO_Central. DR GO; GO:0010460; P:positive regulation of heart rate; ISO:GO_Central. DR GO; GO:0001996; P:positive regulation of heart rate by epinephrine-norepinephrine; IGI:MGI. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IGI:MGI. DR GO; GO:0141214; P:positive regulation of phospholipase C/protein kinase C signal transduction; ISO:GO_Central. DR GO; GO:0045987; P:positive regulation of smooth muscle contraction; IDA:BHF-UCL. DR GO; GO:0032230; P:positive regulation of synaptic transmission, GABAergic; ISO:GO_Central. DR GO; GO:0003084; P:positive regulation of systemic arterial blood pressure; ISO:GO_Central. DR GO; GO:0001997; P:positive regulation of the force of heart contraction by epinephrine-norepinephrine; IGI:MGI. DR GO; GO:0045907; P:positive regulation of vasoconstriction; ISO:GO_Central. DR GO; GO:0099171; P:presynaptic modulation of chemical synaptic transmission; ISO:GO_Central. DR GO; GO:0008217; P:regulation of blood pressure; IMP:MGI. DR GO; GO:0009725; P:response to hormone; ISO:GO_Central. DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:GO_Central. DR CDD; cd15325; 7tmA_alpha1A_AR; 1. DR FunFam; 1.20.1070.10:FF:000027; alpha-1A adrenergic receptor; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR002233; ADR_fam. DR InterPro; IPR001004; ADRA1A_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:SF16; ALPHA-1A ADRENERGIC RECEPTOR; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR01103; ADRENERGICR. DR PRINTS; PR00557; ADRENRGCA1AR. 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; Cytoplasm; Disulfide bond; G protein-coupled receptor; KW Glycoprotein; Lipoprotein; Membrane; Nucleus; Palmitate; Phosphoprotein; KW Receptor; Reference proteome; Transducer; Transmembrane; KW Transmembrane helix. FT CHAIN 1..466 FT /note="Alpha-1A adrenergic receptor" FT /id="PRO_0000069064" FT TOPO_DOM 1..27 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 28..51 FT /note="Helical; Name=1" FT /evidence="ECO:0000250" FT TOPO_DOM 52..64 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 65..88 FT /note="Helical; Name=2" FT /evidence="ECO:0000250" FT TOPO_DOM 89..99 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 100..122 FT /note="Helical; Name=3" FT /evidence="ECO:0000250" FT TOPO_DOM 123..143 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 144..167 FT /note="Helical; Name=4" FT /evidence="ECO:0000250" FT TOPO_DOM 168..181 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 182..205 FT /note="Helical; Name=5" FT /evidence="ECO:0000250" FT TOPO_DOM 206..273 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 274..297 FT /note="Helical; Name=6" FT /evidence="ECO:0000250" FT TOPO_DOM 298..305 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 306..329 FT /note="Helical; Name=7" FT /evidence="ECO:0000250" FT TOPO_DOM 330..466 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT MOTIF 334..349 FT /note="Nuclear localization signal" FT /evidence="ECO:0000250|UniProtKB:P35348" FT BINDING 106 FT /ligand="(R)-adrenaline" FT /ligand_id="ChEBI:CHEBI:71406" FT /evidence="ECO:0000250|UniProtKB:P35348" FT BINDING 188 FT /ligand="(R)-adrenaline" FT /ligand_id="ChEBI:CHEBI:71406" FT /evidence="ECO:0000250|UniProtKB:P35348" FT MOD_RES 215 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000255" FT LIPID 345 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000255" FT CARBOHYD 7 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 13 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 22 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 99..176 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521" FT CONFLICT 369 FT /note="G -> E (in Ref. 1; AAC02658)" FT /evidence="ECO:0000305" FT CONFLICT 395 FT /note="R -> C (in Ref. 1; AAC02658)" FT /evidence="ECO:0000305" SQ SEQUENCE 466 AA; 51744 MW; 8C5FE5C67E885795 CRC64; MVLLSENASE GSNCTHPPAQ VNISKAILLG VILGGLIIFG VLGNILVILS VACHRHLHSV THYYIVNLAV ADLLLTSTVL PFSAIFEILG YWAFGRVFCN IWAAVDVLCC TASIMGLCII SIDRYIGVSY PLRYPTIVTQ RRGVRALLCV WALSLVISIG PLFGWRQQAP EDETICQINE EPGYVLFSAL GSFYVPLTII LVMYCRVYVV AKRESRGLKS GLKTDKSDSE QVTLRIHRKN VPAEGSGVSS AKNKTHFSVR LLKFSREKKA AKTLGIVVGC FVLCWLPFFL VMPIGSFFPN FKPPETVFKI VFWLGYLNSC INPIIYPCSS QEFKKAFQNV LRIQCLRRRQ SSKHALGYTL HPPSQAVEGQ HRGMVRIPVG SGETFYKISK TDGVREWKFF SSMPQGSARI TMPKDQSACT TARVRSKSFL QVCCCVGSST PRPEENHQVP TIKIHTISLG ENGEEV //