ADA1D_HUMAN
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 03-AUG-2022, entry version 182.
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}.
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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 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 GlyGen; P25100; 2 sites.
DR iPTMnet; P25100; -.
DR PhosphoSitePlus; P25100; -.
DR BioMuta; ADRA1D; -.
DR DMDM; 1168243; -.
DR PaxDb; P25100; -.
DR PeptideAtlas; P25100; -.
DR PRIDE; P25100; -.
DR ProteomicsDB; 54255; -.
DR Antibodypedia; 7918; 162 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 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; 1095345at2759; -.
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; 10 hits in 1075 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 descending thoracic aorta and 112 other tissues.
DR ExpressionAtlas; P25100; baseline and differential.
DR Genevisible; P25100; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0004937; F:alpha1-adrenergic receptor activity; IBA:GO_Central.
DR GO; GO:0004930; F:G protein-coupled 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:0001996; P:positive regulation of heart rate by epinephrine-norepinephrine; IBA:GO_Central.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; IBA:GO_Central.
DR InterPro; IPR002233; ADR_fam.
DR InterPro; IPR000363; ADRA1D_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR24248:SF14; PTHR24248:SF14; 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 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; 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
