ID ADA1D_HUMAN Reviewed; 572 AA. AC P25100; Q9NPY0; DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 2. DT 24-JAN-2024, entry version 190. DE RecName: Full=Alpha-1D adrenergic receptor; DE AltName: Full=Alpha-1A adrenergic receptor; DE AltName: Full=Alpha-1D adrenoreceptor; DE Short=Alpha-1D adrenoceptor; DE AltName: Full=Alpha-adrenergic receptor 1a; GN Name=ADRA1D; Synonyms=ADRA1A; 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 [MRNA]. RC TISSUE=Hippocampus; RX PubMed=1656955; DOI=10.1016/0006-291x(91)91740-4; RA Bruno J.F., Whittaker J., Song J., Berelowitz M.; RT "Molecular cloning and sequencing of a cDNA encoding a human alpha 1A RT adrenergic receptor."; RL Biochem. Biophys. Res. Commun. 179:1485-1490(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Hippocampus; RX PubMed=8183249; RA Forray C., Bard J.A., Wetzel J.M., Chiu G., Shapiro E., Tang R., Lepor H., RA Hartig P.R., Weinshank R.L., Branchek T.A., Gluchowski C.; RT "The alpha 1-adrenergic receptor that mediates smooth muscle contraction in RT human prostate has the pharmacological properties of the cloned human alpha RT 1c subtype."; RL Mol. Pharmacol. 45:703-708(1994). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=7815325; RA Schwinn D.A., Johnston G.I., Page S.O., Mosley M.J., Wilson K.H., RA Worman N.P., Campbell S., Fidock M.D., Furness L.M., Parry-Smith D.J., RA Peter B., Bailey D.S.; RT "Cloning and pharmacological characterization of human alpha-1 adrenergic RT receptors: sequence corrections and direct comparison with other species RT homologues."; RL J. Pharmacol. Exp. Ther. 272:134-142(1995). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8024574; DOI=10.1006/bbrc.1994.1845; RA Weinberg D.H., Trivedi P., Tan C.P., Mitra S., Perkins-Barrow A., RA Borkowski D., Strader C.D., Bayne M.; RT "Cloning, expression and characterization of human alpha adrenergic RT receptors alpha 1a, alpha 1b and alpha 1c."; RL Biochem. Biophys. Res. Commun. 201:1296-1304(1994). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Placenta, and Prostate; RX PubMed=7746284; RA Esbenshade T.A., Hirasawa A., Tsujimoto G., Tanaka T., Yano J., RA Minneman K.P., Murphy T.J.; RT "Cloning of the human alpha 1d-adrenergic receptor and inducible expression RT of three human subtypes in SK-N-MC cells."; RL Mol. Pharmacol. 47:977-985(1995). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [7] RP INTERACTION WITH FLNA. RX PubMed=26460884; DOI=10.1021/acs.biochem.5b00975; RA Tirupula K.C., Ithychanda S.S., Mohan M.L., Naga Prasad S.V., Qin J., RA Karnik S.S.; RT "G Protein-Coupled Receptors Directly Bind Filamin A with High Affinity and RT Promote Filamin Phosphorylation."; RL Biochemistry 54:6673-6683(2015). CC -!- FUNCTION: This alpha-adrenergic receptor mediates its effect through CC the influx of extracellular calcium. CC -!- SUBUNIT: Interacts with FLNA (via filamin repeat 21); increases PKA- CC mediated phosphorylation of FLNA. {ECO:0000269|PubMed:26460884}. CC -!- INTERACTION: CC P25100; P25100: ADRA1D; NbExp=5; IntAct=EBI-489993, EBI-489993; CC P25100; Q14160: SCRIB; NbExp=19; IntAct=EBI-489993, EBI-357345; CC P25100; Q13424: SNTA1; NbExp=11; IntAct=EBI-489993, EBI-717191; CC P25100; Q13425: SNTB2; NbExp=16; IntAct=EBI-489993, EBI-80411; CC P25100; Q61234: Snta1; Xeno; NbExp=3; IntAct=EBI-489993, EBI-295952; CC P25100; Q99L88: Sntb1; Xeno; NbExp=2; IntAct=EBI-489993, EBI-295943; CC P25100; Q925E0: Sntg2; Xeno; NbExp=2; IntAct=EBI-489993, EBI-8521556; CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. CC -!- PTM: Palmitoylated. Palmitoylation by ZDHHC21 may increase the CC expression of the receptor and regulate downstream signaling. CC {ECO:0000250|UniProtKB:P97714}. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC Adrenergic receptor subfamily. ADRA1D sub-subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. 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; M76446; AAA35496.1; -; mRNA. DR EMBL; U03864; AAB60351.1; -; mRNA. DR EMBL; L31772; AAB59487.1; -; mRNA. DR EMBL; S70782; AAB31163.2; -; mRNA. DR EMBL; D29952; BAA06222.1; -; Genomic_DNA. DR EMBL; AL121675; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL357040; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS13079.1; -. DR PIR; I39369; I39369. DR PIR; JH0447; JH0447. DR RefSeq; NP_000669.1; NM_000678.3. DR AlphaFoldDB; P25100; -. DR EMDB; EMD-33924; -. DR EMDB; EMD-33928; -. DR EMDB; EMD-9376; -. DR SMR; P25100; -. DR BioGRID; 106656; 16. DR IntAct; P25100; 29. DR MINT; P25100; -. DR STRING; 9606.ENSP00000368766; -. DR BindingDB; P25100; -. DR ChEMBL; CHEMBL223; -. DR DrugBank; DB00346; Alfuzosin. DR DrugBank; DB00321; Amitriptyline. DR DrugBank; DB00543; Amoxapine. DR DrugBank; DB00182; Amphetamine. DR DrugBank; DB09229; Aranidipine. DR DrugBank; DB09204; Arotinolol. DR DrugBank; DB01200; Bromocriptine. DR DrugBank; DB00490; Buspirone. DR DrugBank; DB00248; Cabergoline. DR DrugBank; DB01136; Carvedilol. DR DrugBank; DB00477; Chlorpromazine. DR DrugBank; DB09202; Cirazoline. DR DrugBank; DB00575; Clonidine. DR DrugBank; DB00298; Dapiprazole. DR DrugBank; DB01151; Desipramine. DR DrugBank; DB01576; Dextroamphetamine. DR DrugBank; DB11273; Dihydroergocornine. DR DrugBank; DB13345; Dihydroergocristine. DR DrugBank; DB00320; Dihydroergotamine. DR DrugBank; DB11278; DL-Methylephedrine. DR DrugBank; DB00841; Dobutamine. DR DrugBank; DB09167; Dosulepin. DR DrugBank; DB00590; Doxazosin. DR DrugBank; DB01142; Doxepin. DR DrugBank; DB04855; Dronedarone. DR DrugBank; DB06262; Droxidopa. DR DrugBank; DB05492; Epicept NP-1. DR DrugBank; DB00668; Epinephrine. DR DrugBank; DB01049; Ergoloid mesylate. DR DrugBank; DB00696; Ergotamine. DR DrugBank; DB01175; Escitalopram. DR DrugBank; DB09194; Etoperidone. DR DrugBank; DB00800; Fenoldopam. DR DrugBank; DB00458; Imipramine. DR DrugBank; DB11577; Indigotindisulfonic acid. DR DrugBank; DB00598; Labetalol. DR DrugBank; DB09195; Lorpiprazole. DR DrugBank; DB00934; Maprotiline. DR DrugBank; DB01365; Mephentermine. DR DrugBank; DB01403; Methotrimeprazine. DR DrugBank; DB00723; Methoxamine. DR DrugBank; DB06148; Mianserin. DR DrugBank; DB00211; Midodrine. DR DrugBank; DB00370; Mirtazapine. DR DrugBank; DB09205; Moxisylyte. DR DrugBank; DB00622; Nicardipine. DR DrugBank; DB00368; Norepinephrine. DR DrugBank; DB00540; Nortriptyline. DR DrugBank; DB06229; Ocaperidone. DR DrugBank; DB00935; Oxymetazoline. DR DrugBank; DB00715; Paroxetine. DR DrugBank; DB01186; Pergolide. DR DrugBank; DB08922; Perospirone. DR DrugBank; DB00925; Phenoxybenzamine. DR DrugBank; DB00692; Phentolamine. DR DrugBank; DB00388; Phenylephrine. DR DrugBank; DB09286; Pipamperone. DR DrugBank; DB06153; Pizotifen. DR DrugBank; DB00457; Prazosin. DR DrugBank; DB00433; Prochlorperazine. DR DrugBank; DB01069; Promethazine. DR DrugBank; DB01224; Quetiapine. DR DrugBank; DB00908; Quinidine. DR DrugBank; DB05469; R450. DR DrugBank; DB11124; Racepinephrine. DR DrugBank; DB00243; Ranolazine. DR DrugBank; DB00268; Ropinirole. DR DrugBank; DB06144; Sertindole. DR DrugBank; DB06207; Silodosin. DR DrugBank; DB09203; Synephrine. DR DrugBank; DB00706; Tamsulosin. DR DrugBank; DB01162; Terazosin. DR DrugBank; DB06764; Tetryzoline. DR DrugBank; DB13025; Tiapride. DR DrugBank; DB00697; Tizanidine. DR DrugBank; DB00661; Verapamil. DR DrugBank; DB06694; Xylometazoline. DR DrugCentral; P25100; -. DR GuidetoPHARMACOLOGY; 24; -. DR GlyCosmos; P25100; 2 sites, No reported glycans. DR GlyGen; P25100; 2 sites. DR iPTMnet; P25100; -. DR PhosphoSitePlus; P25100; -. DR BioMuta; ADRA1D; -. DR DMDM; 1168243; -. DR MassIVE; P25100; -. DR PaxDb; 9606-ENSP00000368766; -. DR PeptideAtlas; P25100; -. DR ProteomicsDB; 54255; -. DR Antibodypedia; 7918; 176 antibodies from 33 providers. DR DNASU; 146; -. DR Ensembl; ENST00000379453.6; ENSP00000368766.4; ENSG00000171873.8. DR GeneID; 146; -. DR KEGG; hsa:146; -. DR MANE-Select; ENST00000379453.6; ENSP00000368766.4; NM_000678.4; NP_000669.1. DR UCSC; uc002wkr.3; human. DR AGR; HGNC:280; -. DR CTD; 146; -. DR DisGeNET; 146; -. DR GeneCards; ADRA1D; -. DR HGNC; HGNC:280; ADRA1D. DR HPA; ENSG00000171873; Tissue enhanced (brain, cervix). DR MIM; 104219; gene. DR neXtProt; NX_P25100; -. DR OpenTargets; ENSG00000171873; -. DR PharmGKB; PA24597; -. DR VEuPathDB; HostDB:ENSG00000171873; -. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT00940000160795; -. DR HOGENOM; CLU_009579_11_6_1; -. DR InParanoid; P25100; -. DR OMA; GATCQAY; -. DR OrthoDB; 4073525at2759; -. DR PhylomeDB; P25100; -. DR TreeFam; TF331895; -. DR PathwayCommons; P25100; -. DR Reactome; R-HSA-390696; Adrenoceptors. DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR Reactome; R-HSA-416482; G alpha (12/13) signalling events. DR SignaLink; P25100; -. DR SIGNOR; P25100; -. DR BioGRID-ORCS; 146; 11 hits in 1157 CRISPR screens. DR ChiTaRS; ADRA1D; human. DR GeneWiki; Alpha-1D_adrenergic_receptor; -. DR GenomeRNAi; 146; -. DR Pharos; P25100; Tclin. DR PRO; PR:P25100; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; P25100; Protein. DR Bgee; ENSG00000171873; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 114 other cell types or tissues. DR ExpressionAtlas; P25100; baseline and differential. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0004937; F:alpha1-adrenergic receptor activity; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0071880; P:adenylate cyclase-activating adrenergic receptor signaling pathway; IBA:GO_Central. DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; TAS:ProtInc. DR GO; GO:0007267; P:cell-cell signaling; IBA:GO_Central. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc. DR GO; GO:0150099; P:neuron-glial cell signaling; ISS:ARUK-UCL. DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IBA:GO_Central. DR GO; GO:0008284; P:positive regulation of cell population proliferation; TAS:ProtInc. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IBA:GO_Central. DR GO; GO:0045907; P:positive regulation of vasoconstriction; IBA:GO_Central. DR CDD; cd15327; 7tmA_alpha1D_AR; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR002233; ADR_fam. DR InterPro; IPR000363; ADRA1D_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:SF14; ALPHA-1D ADRENERGIC RECEPTOR; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR01103; ADRENERGICR. DR PRINTS; PR00240; ADRENRGCA1DR. 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. DR Genevisible; P25100; HS. PE 1: Evidence at protein level; KW Cell membrane; G-protein coupled receptor; Glycoprotein; Lipoprotein; KW Membrane; Palmitate; Receptor; Reference proteome; Transducer; KW Transmembrane; Transmembrane helix. FT CHAIN 1..572 FT /note="Alpha-1D adrenergic receptor" FT /id="PRO_0000069073" FT TOPO_DOM 1..95 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 96..121 FT /note="Helical; Name=1" FT /evidence="ECO:0000250" FT TOPO_DOM 122..133 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 134..159 FT /note="Helical; Name=2" FT /evidence="ECO:0000250" FT TOPO_DOM 160..169 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 170..192 FT /note="Helical; Name=3" FT /evidence="ECO:0000250" FT TOPO_DOM 193..213 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 214..238 FT /note="Helical; Name=4" FT /evidence="ECO:0000250" FT TOPO_DOM 239..251 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 252..275 FT /note="Helical; Name=5" FT /evidence="ECO:0000250" FT TOPO_DOM 276..348 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 349..373 FT /note="Helical; Name=6" FT /evidence="ECO:0000250" FT TOPO_DOM 374..380 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 381..405 FT /note="Helical; Name=7" FT /evidence="ECO:0000250" FT TOPO_DOM 406..572 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT REGION 1..77 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 444..488 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 463..479 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT LIPID 419 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000255" FT CARBOHYD 65 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 82 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CONFLICT 1..83 FT /note="MTFRDLLSVSFEGPRPDSSAGGSSAGGGGGSAGGAAPSEGPAVGGVPGGAGG FT GGGVVGAGSGEDNRSSAGEPGSAGAGGDVNG -> MAAALRSVMMAGYLSEWRTPTYRS FT TEMVQRLRMEAVQHSTS (in Ref. 1)" FT /evidence="ECO:0000305" FT CONFLICT 31 FT /note="S -> G (in Ref. 4; AAB31163)" FT /evidence="ECO:0000305" FT CONFLICT 489..572 FT /note="KPPSAFREWRLLGPFRRPTTQLRAKVSSLSHKIRAGGAQRAEAACAQRSEVE FT AVSLGVPHEVAEGATCQAYELADYSNLRETDI -> SHPAPSASGGCWGRSGDPRPSCA FT PKSPACRTRSPPGARSAQRQRAPSAQRWRLCP (in Ref. 1)" FT /evidence="ECO:0000305" FT CONFLICT 522 FT /note="R -> P (in Ref. 4; AAB31163)" FT /evidence="ECO:0000305" SQ SEQUENCE 572 AA; 60463 MW; EBEB134CF20A4988 CRC64; MTFRDLLSVS FEGPRPDSSA GGSSAGGGGG SAGGAAPSEG PAVGGVPGGA GGGGGVVGAG SGEDNRSSAG EPGSAGAGGD VNGTAAVGGL VVSAQGVGVG VFLAAFILMA VAGNLLVILS VACNRHLQTV TNYFIVNLAV ADLLLSATVL PFSATMEVLG FWAFGRAFCD VWAAVDVLCC TASILSLCTI SVDRYVGVRH SLKYPAIMTE RKAAAILALL WVVALVVSVG PLLGWKEPVP PDERFCGITE EAGYAVFSSV CSFYLPMAVI VVMYCRVYVV ARSTTRSLEA GVKRERGKAS EVVLRIHCRG AATGADGAHG MRSAKGHTFR SSLSVRLLKF SREKKAAKTL AIVVGVFVLC WFPFFFVLPL GSLFPQLKPS EGVFKVIFWL GYFNSCVNPL IYPCSSREFK RAFLRLLRCQ CRRRRRRRPL WRVYGHHWRA STSGLRQDCA PSSGDAPPGA PLALTALPDP DPEPPGTPEM QAPVASRRKP PSAFREWRLL GPFRRPTTQL RAKVSSLSHK IRAGGAQRAE AACAQRSEVE AVSLGVPHEV AEGATCQAYE LADYSNLRET DI //