ID DRD2_HUMAN Reviewed; 443 AA. AC P14416; Q9NZR3; Q9UPA9; DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1990, sequence version 2. DT 24-JAN-2024, entry version 244. DE RecName: Full=D(2) dopamine receptor; DE AltName: Full=Dopamine D2 receptor; GN Name=DRD2; 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] (ISOFORM 1). RX PubMed=2533064; DOI=10.1089/dna.1.1989.8.683; RA Selbie L.A., Hayes G., Shine J.; RT "The major dopamine D2 receptor: molecular analysis of the human D2A RT subtype."; RL DNA 8:683-689(1989). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), AND TISSUE RP SPECIFICITY. RX PubMed=2531656; DOI=10.1002/j.1460-2075.1989.tb08585.x; RA Dal-Toso R., Sommer B., Ewert M., Herb A., Pritchett D.B., Bach A., RA Shivers B.D., Seeburg P.H.; RT "The dopamine D2 receptor: two molecular forms generated by alternative RT splicing."; RL EMBO J. 8:4025-4034(1989). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Retina; RX PubMed=2138729; DOI=10.1093/nar/18.5.1299; RA Robakis N.K., Mohamadi M., Fu D.Y., Sambamurti K., Refolo L.M.; RT "Human retina D2 receptor cDNAs have multiple polyadenylation sites and RT differ from a pituitary clone at the 5' non-coding region."; RL Nucleic Acids Res. 18:1299-1299(1990). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=2532362; DOI=10.1073/pnas.86.24.9762; RA Grandy D.K., Marchionni M.A., Makam H., Stofko R.E., Alfano M., RA Frothingham L., Fischer J.B., Burke-Howie K.J., Bunzow J.R., Server A.C., RA Civelli O.; RT "Cloning of the cDNA and gene for a human D2 dopamine receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 86:9762-9766(1989). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Retina; RX PubMed=2137193; RA Stormann T.M., Gdula D.C., Weiner D.M., Brann M.R.; RT "Molecular cloning and expression of a dopamine D2 receptor from human RT retina."; RL Mol. Pharmacol. 37:1-6(1990). RN [6] RP NUCLEOTIDE SEQUENCE (ISOFORM 1). RX PubMed=2144985; RA Selbie L.A., Hayes G., Shine J.; RT "DNA homology screening: isolation and characterization of the human D2A RT dopamine receptor subtype."; RL Adv. Second Messenger Phosphoprotein Res. 24:9-14(1990). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1363862; DOI=10.1016/0197-0186(92)90071-x; RA Araki K., Kuwano R., Morii K., Hayashi S., Minoshima S., Shimizu N., RA Katagiri T., Usui H., Kumanishi T., Takahashi Y.; RT "Structure and expression of human and rat D2 dopamine receptor genes."; RL Neurochem. Int. 21:91-98(1992). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Retina; RX PubMed=1835903; DOI=10.1007/bf00734808; RA Dearry A., Falardeau P., Shores C., Caron M.G.; RT "D2 dopamine receptors in the human retina: cloning of cDNA and RT localization of mRNA."; RL Cell. Mol. Neurobiol. 11:437-453(1991). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=8471125; DOI=10.1038/npp.1993.15; RA Seeman P., Ohara K., Ulpian C., Seeman M.V., Jellinger K., Tol H.H., RA Niznik H.B.; RT "Schizophrenia: normal sequence in the dopamine D2 receptor region that RT couples to G-proteins. DNA polymorphisms in D2."; RL Neuropsychopharmacology 8:137-142(1993). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RC TISSUE=Corpus striatum; RX PubMed=10719223; DOI=10.1016/s0169-328x(99)00343-5; RA Seeman P., Nam D., Ulpian C., Liu I.S.C., Tallerico T.; RT "New dopamine receptor, D2(Longer), with unique TG splice site, in human RT brain."; RL Brain Res. Mol. Brain Res. 76:132-141(2000). RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3). RA Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S., RA Tsutsumi S., Aburatani H., Asai K., Akiyama Y.; RT "Genome-wide discovery and analysis of human seven transmembrane helix RT receptor genes."; RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE (ISOFORM 1). RA Kidd K.K.; RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases. RN [13] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung; 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 [14] RP INTERACTION WITH CADPS AND CADPS2. RX PubMed=15857609; DOI=10.1016/j.bcp.2005.02.015; RA Binda A.V., Kabbani N., Levenson R.; RT "Regulation of dense core vesicle release from PC12 cells by interaction RT between the D2 dopamine receptor and calcium-dependent activator protein RT for secretion (CAPS)."; RL Biochem. Pharmacol. 69:1451-1461(2005). RN [15] RP INTERACTION WITH GNAI2. RX PubMed=17550964; DOI=10.1242/jcs.005611; RA Lopez-Aranda M.F., Acevedo M.J., Gutierrez A., Koulen P., Khan Z.U.; RT "Role of a Galphai2 protein splice variant in the formation of an RT intracellular dopamine D2 receptor pool."; RL J. Cell Sci. 120:2171-2178(2007). RN [16] RP HOMOOLIGOMERIZATION, AND INTERACTION WITH DRD4. RX PubMed=21184734; DOI=10.1016/j.bbrc.2010.12.083; RA Borroto-Escuela D.O., Van Craenenbroeck K., Romero-Fernandez W., RA Guidolin D., Woods A.S., Rivera A., Haegeman G., Agnati L.F., RA Tarakanov A.O., Fuxe K.; RT "Dopamine D2 and D4 receptor heteromerization and its allosteric receptor- RT receptor interactions."; RL Biochem. Biophys. Res. Commun. 404:928-934(2011). RN [17] RP INTERACTION WITH HTR2A, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=21645528; DOI=10.1016/j.neuropharm.2011.05.023; RA Albizu L., Holloway T., Gonzalez-Maeso J., Sealfon S.C.; RT "Functional crosstalk and heteromerization of serotonin 5-HT2A and dopamine RT D2 receptors."; RL Neuropharmacology 61:770-777(2011). RN [18] RP RETRACTED PAPER. RX PubMed=17264214; DOI=10.1073/pnas.0608599104; RA Johnston C.A., Siderovski D.P.; RT "Structural basis for nucleotide exchange on G alpha i subunits and RT receptor coupling specificity."; RL Proc. Natl. Acad. Sci. U.S.A. 104:2001-2006(2007). RN [19] RP RETRACTION NOTICE OF PUBMED:17264214. RX PubMed=22408789; DOI=10.1073/pnas.1200173109; RA Johnston C.A., Siderovski D.P.; RL Proc. Natl. Acad. Sci. U.S.A. 109:1808-1808(2012). RN [20] RP SUBCELLULAR LOCATION, PALMITOYLATION AT CYS-443, AND MUTAGENESIS OF RP CYS-126; CYS-244; CYS-253 AND CYS-443. RX PubMed=26535572; DOI=10.1371/journal.pone.0140661; RA Ebersole B., Petko J., Woll M., Murakami S., Sokolina K., Wong V., RA Stagljar I., Luescher B., Levenson R.; RT "Effect of C-Terminal S-Palmitoylation on D2 Dopamine Receptor Trafficking RT and Stability."; RL PLoS ONE 10:e0140661-e0140661(2015). RN [21] {ECO:0007744|PDB:5AER} RP X-RAY CRYSTALLOGRAPHY (2.19 ANGSTROMS) OF 430-443 IN COMPLEX WITH NCS1. RX PubMed=25979333; DOI=10.1074/jbc.m114.627059; RA Pandalaneni S., Karuppiah V., Saleem M., Haynes L.P., Burgoyne R.D., RA Mayans O., Derrick J.P., Lian L.Y.; RT "Neuronal Calcium Sensor-1 Binds the D2 Dopamine Receptor and G-protein- RT coupled Receptor Kinase 1 (GRK1) Peptides Using Different Modes of RT Interactions."; RL J. Biol. Chem. 290:18744-18756(2015). RN [22] {ECO:0007744|PDB:6CM4} RP X-RAY CRYSTALLOGRAPHY (2.87 ANGSTROMS) OF 35-222 AND 363-443 IN COMPLEX RP WITH INVERSE AGONIST RISPERIDONE, AND DISULFIDE BONDS. RX PubMed=29466326; DOI=10.1038/nature25758; RA Wang S., Che T., Levit A., Shoichet B.K., Wacker D., Roth B.L.; RT "Structure of the D2 dopamine receptor bound to the atypical antipsychotic RT drug risperidone."; RL Nature 555:269-273(2018). RN [23] RP VARIANT CYS-311. RX PubMed=7902708; DOI=10.1006/bbrc.1993.2404; RA Itokawa M., Arinami T., Futamura N., Hamaguchi H., Toru M.; RT "A structural polymorphism of human dopamine D2 receptor, RT D2(Ser311->Cys)."; RL Biochem. Biophys. Res. Commun. 196:1369-1375(1993). RN [24] RP VARIANT ILE-154. RX PubMed=10220438; DOI=10.1073/pnas.96.9.5173; RA Klein C., Brin M.F., Kramer P., Sena-Esteves M., de Leon D., Doheny D., RA Bressman S., Fahn S., Breakefield X.O., Ozelius L.J.; RT "Association of a missense change in the D2 dopamine receptor with RT myoclonus dystonia."; RL Proc. Natl. Acad. Sci. U.S.A. 96:5173-5176(1999). RN [25] RP INVOLVEMENT IN SUSCEPTIBILITY TO ALCOHOLISM. RX PubMed=15389757; DOI=10.1002/ajmg.b.30085; RA Johann M., Putzhammer A., Eichhammer P., Wodarz N.; RT "Association of the -141C Del variant of the dopamine D2 receptor (DRD2) RT with positive family history and suicidality in German alcoholics."; RL Am. J. Med. Genet. B Neuropsychiatr. Genet. 132:46-49(2005). RN [26] RP CHARACTERIZATION OF VARIANT ILE-154. RX PubMed=10716258; RX DOI=10.1002/1531-8249(200003)47:3<369::aid-ana14>3.3.co;2-0; RA Klein C., Gurvich N., Sena-Esteves M., Bressman S., Brin M.F., RA Ebersole B.J., Fink S., Forsgren L., Friedman J., Grimes D., Holmgren G., RA Kyllerman M., Lang A.E., de Leon D., Leung J., Prioleau C., Raymond D., RA Sanner G., Saunders-Pullman R., Vieregge P., Wahlstrom J., RA Breakefield X.O., Kramer P.L., Ozelius L.J., Sealfon S.C.; RT "Evaluation of the role of the D2 dopamine receptor in myoclonus RT dystonia."; RL Ann. Neurol. 47:369-373(2000). RN [27] RP VARIANT GLU-327. RX PubMed=21179162; DOI=10.1038/nature09629; RA Bevilacqua L., Doly S., Kaprio J., Yuan Q., Tikkanen R., Paunio T., RA Zhou Z., Wedenoja J., Maroteaux L., Diaz S., Belmer A., Hodgkinson C.A., RA Dell'osso L., Suvisaari J., Coccaro E., Rose R.J., Peltonen L., RA Virkkunen M., Goldman D.; RT "A population-specific HTR2B stop codon predisposes to severe RT impulsivity."; RL Nature 468:1061-1066(2010). CC -!- FUNCTION: Dopamine receptor whose activity is mediated by G proteins CC which inhibit adenylyl cyclase (PubMed:21645528). Positively regulates CC postnatal regression of retinal hyaloid vessels via suppression of CC VEGFR2/KDR activity, downstream of OPN5 (By similarity). CC {ECO:0000250|UniProtKB:P61168, ECO:0000269|PubMed:21645528}. CC -!- SUBUNIT: Forms homo- and heterooligomers with DRD4 (PubMed:21184734). CC The interaction with DRD4 may modulate agonist-induced downstream CC signaling (PubMed:21184734). Interacts with CADPS and CADPS2 CC (PubMed:15857609). Interacts with GPRASP1, PPP1R9B and CLIC6 (By CC similarity). Interacts with ARRB2 (By similarity). Interacts with HTR2A CC (PubMed:21645528). Interacts with GNAI2 isoform sGi2, the interaction CC allows the creation of an intracellular pool of DRD2 that can be CC released to cell surface upon agonist stimulation (PubMed:17550964). CC Interacts with DRD1 (By similarity). Interacts with KCNA2 (By CC similarity). {ECO:0000250|UniProtKB:P61168, CC ECO:0000250|UniProtKB:P61169}. CC -!- INTERACTION: CC P14416; Q9NRI5: DISC1; NbExp=3; IntAct=EBI-2928178, EBI-529989; CC P14416; P14416: DRD2; NbExp=9; IntAct=EBI-2928178, EBI-2928178; CC P14416; Q01959: SLC6A3; NbExp=4; IntAct=EBI-2928178, EBI-6661445; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21645528, CC ECO:0000269|PubMed:26535572}; Multi-pass membrane protein CC {ECO:0000255}. Golgi apparatus membrane {ECO:0000269|PubMed:26535572}; CC Multi-pass membrane protein {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=D2(Long), D2A; CC IsoId=P14416-1; Sequence=Displayed; CC Name=2; Synonyms=D2(Short), D2B; CC IsoId=P14416-2; Sequence=VSP_001870; CC Name=3; Synonyms=D2(Longer); CC IsoId=P14416-3; Sequence=VSP_026455; CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed in the anterior pituitary CC gland. {ECO:0000269|PubMed:2531656}. CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in the anterior pituitary CC gland. {ECO:0000269|PubMed:2531656}. CC -!- PTM: Palmitoylated. Palmitoylation which is required for proper CC localization to the plasma membrane and stability of the receptor could CC be carried on by ZDHHC4, ZDHHC3 and ZDHHC8. CC {ECO:0000269|PubMed:26535572}. CC -!- POLYMORPHISM: Genetic variations in DRD2 may determine the genetic CC susceptibility to alcoholism [MIM:103780]. Genetic variations in DRD2 CC might be a protective factor against the development of withdrawal CC symptoms but might also be a risk factor in a highly burdened subgroup CC of alcoholics with a paternal and grandpaternal history of alcoholism CC and might contribute to suicide risk in alcoholics. CC {ECO:0000305|PubMed:15389757}. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. 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; M30625; AAA88024.1; -; mRNA. DR EMBL; X51645; CAB56463.1; -; mRNA. DR EMBL; X51646; CAB37869.1; -; Genomic_DNA. DR EMBL; X51362; CAA35746.1; -; mRNA. DR EMBL; M29066; AAA52761.1; -; mRNA. DR EMBL; S62137; AAB26819.1; -; mRNA. DR EMBL; S69899; AAB20571.1; -; mRNA. DR EMBL; S58589; AAB26274.1; -; Genomic_DNA. DR EMBL; S58577; AAB26274.1; JOINED; Genomic_DNA. DR EMBL; S58584; AAB26274.1; JOINED; Genomic_DNA. DR EMBL; S58586; AAB26274.1; JOINED; Genomic_DNA. DR EMBL; S58588; AAB26274.1; JOINED; Genomic_DNA. DR EMBL; AF176812; AAF61479.1; -; mRNA. DR EMBL; AB065860; BAC06078.1; -; Genomic_DNA. DR EMBL; AF050737; AAC78779.1; -; Genomic_DNA. DR EMBL; BC021195; AAH21195.1; -; mRNA. DR CCDS; CCDS8361.1; -. [P14416-1] DR CCDS; CCDS8362.1; -. [P14416-2] DR PIR; S08417; DYHUD2. DR RefSeq; NP_000786.1; NM_000795.3. [P14416-1] DR RefSeq; NP_057658.2; NM_016574.3. [P14416-2] DR RefSeq; XP_016872785.1; XM_017017296.1. [P14416-1] DR PDB; 5AER; X-ray; 2.19 A; B/C=430-443. DR PDB; 6CM4; X-ray; 2.87 A; A=35-222, A=363-443. DR PDB; 6LUQ; X-ray; 3.10 A; A=35-222, A=367-443. DR PDB; 6VMS; EM; 3.80 A; R=29-443. DR PDB; 7DFP; X-ray; 3.10 A; A=34-238, A=364-443. DR PDB; 7JVR; EM; 2.80 A; R=1-443. DR PDB; 8IRS; EM; 3.00 A; R=1-443. DR PDBsum; 5AER; -. DR PDBsum; 6CM4; -. DR PDBsum; 6LUQ; -. DR PDBsum; 6VMS; -. DR PDBsum; 7DFP; -. DR PDBsum; 7JVR; -. DR PDBsum; 8IRS; -. DR AlphaFoldDB; P14416; -. DR EMDB; EMD-21243; -. DR EMDB; EMD-22511; -. DR EMDB; EMD-35684; -. DR SMR; P14416; -. DR BioGRID; 108147; 98. DR CORUM; P14416; -. DR DIP; DIP-5977N; -. DR IntAct; P14416; 78. DR MINT; P14416; -. DR STRING; 9606.ENSP00000354859; -. DR BindingDB; P14416; -. DR ChEMBL; CHEMBL217; -. DR DrugBank; DB01614; Acepromazine. DR DrugBank; DB01063; Acetophenazine. DR DrugBank; DB01425; Alizapride. DR DrugBank; DB00915; Amantadine. DR DrugBank; DB06288; Amisulpride. DR DrugBank; DB05964; Amitifadine. DR DrugBank; DB00543; Amoxapine. DR DrugBank; DB00182; Amphetamine. DR DrugBank; DB04599; Aniracetam. DR DrugBank; DB00714; Apomorphine. DR DrugBank; DB01238; Aripiprazole. DR DrugBank; DB14185; Aripiprazole lauroxil. DR DrugBank; DB09207; AS-8112. DR DrugBank; DB06216; Asenapine. DR DrugBank; DB04889; Bicifadine. DR DrugBank; DB04888; Bifeprunox. DR DrugBank; DB05687; BL-1020. DR DrugBank; DB09223; Blonanserin. DR DrugBank; DB04857; Brasofensine. DR DrugBank; DB09128; Brexpiprazole. DR DrugBank; DB01200; Bromocriptine. DR DrugBank; DB09018; Bromopride. DR DrugBank; DB00490; Buspirone. DR DrugBank; DB00248; Cabergoline. DR DrugBank; DB06016; Cariprazine. DR DrugBank; DB01038; Carphenazine. DR DrugBank; DB00477; Chlorpromazine. DR DrugBank; DB01239; Chlorprothixene. DR DrugBank; DB00568; Cinnarizine. DR DrugBank; DB00363; Clozapine. DR DrugBank; DB01151; Desipramine. DR DrugBank; DB11274; Dihydro-alpha-ergocryptine. DR DrugBank; DB13345; Dihydroergocristine. DR DrugBank; DB00320; Dihydroergotamine. DR DrugBank; DB01184; Domperidone. DR DrugBank; DB00988; Dopamine. DR DrugBank; DB00450; Droperidol. DR DrugBank; DB11275; Epicriptine. DR DrugBank; DB01049; Ergoloid mesylate. DR DrugBank; DB00696; Ergotamine. DR DrugBank; DB01175; Escitalopram. DR DrugBank; DB09194; Etoperidone. DR DrugBank; DB00875; Flupentixol. DR DrugBank; DB00623; Fluphenazine. DR DrugBank; DB04842; Fluspirilene. DR DrugBank; DB00502; Haloperidol. DR DrugBank; DB04946; Iloperidone. DR DrugBank; DB00458; Imipramine. DR DrugBank; DB04924; Itopride. DR DrugBank; DB12579; JNJ-37822681. DR DrugBank; DB01221; Ketamine. DR DrugBank; DB00555; Lamotrigine. DR DrugBank; DB01235; Levodopa. DR DrugBank; DB00589; Lisuride. DR DrugBank; DB00408; Loxapine. DR DrugBank; DB06077; Lumateperone. DR DrugBank; DB08815; Lurasidone. DR DrugBank; DB00934; Maprotiline. DR DrugBank; DB09224; Melperone. DR DrugBank; DB01043; Memantine. DR DrugBank; DB00933; Mesoridazine. DR DrugBank; DB01403; Methotrimeprazine. DR DrugBank; DB01233; Metoclopramide. DR DrugBank; DB06148; Mianserin. DR DrugBank; DB00805; Minaprine. DR DrugBank; DB01618; Molindone. DR DrugBank; DB08804; Nandrolone decanoate. DR DrugBank; DB05766; Norclozapine. DR DrugBank; DB00540; Nortriptyline. DR DrugBank; DB06229; Ocaperidone. DR DrugBank; DB00334; Olanzapine. DR DrugBank; DB01267; Paliperidone. DR DrugBank; DB12061; Pardoprunox. DR DrugBank; DB00715; Paroxetine. DR DrugBank; DB01186; Pergolide. DR DrugBank; DB08922; Perospirone. DR DrugBank; DB00850; Perphenazine. DR DrugBank; DB01100; Pimozide. DR DrugBank; DB09286; Pipamperone. DR DrugBank; DB01621; Pipotiazine. DR DrugBank; DB12478; Piribedil. DR DrugBank; DB00413; Pramipexole. DR DrugBank; DB00433; Prochlorperazine. DR DrugBank; DB00420; Promazine. DR DrugBank; DB01069; Promethazine. DR DrugBank; DB00777; Propiomazine. DR DrugBank; DB01224; Quetiapine. DR DrugBank; DB09097; Quinagolide. DR DrugBank; DB12518; Raclopride. DR DrugBank; DB00409; Remoxipride. DR DrugBank; DB00734; Risperidone. DR DrugBank; DB01549; Rolicyclidine. DR DrugBank; DB00268; Ropinirole. DR DrugBank; DB05271; Rotigotine. DR DrugBank; DB06454; Sarizotan. DR DrugBank; DB06144; Sertindole. DR DrugBank; DB00391; Sulpiride. DR DrugBank; DB06477; Sumanirole. DR DrugBank; DB04844; Tetrabenazine. DR DrugBank; DB12093; Tetrahydropalmatine. DR DrugBank; DB00372; Thiethylperazine. DR DrugBank; DB01622; Thioproperazine. DR DrugBank; DB00679; Thioridazine. DR DrugBank; DB01623; Thiothixene. DR DrugBank; DB13025; Tiapride. DR DrugBank; DB00831; Trifluoperazine. DR DrugBank; DB00508; Triflupromazine. DR DrugBank; DB00726; Trimipramine. DR DrugBank; DB06109; YKP-1358. DR DrugBank; DB01392; Yohimbine. DR DrugBank; DB00246; Ziprasidone. DR DrugBank; DB09225; Zotepine. DR DrugBank; DB01624; Zuclopenthixol. DR DrugCentral; P14416; -. DR GuidetoPHARMACOLOGY; 215; -. DR TCDB; 9.A.14.3.10; the g-protein-coupled receptor (gpcr) family. DR GlyCosmos; P14416; 3 sites, No reported glycans. DR GlyGen; P14416; 3 sites. DR iPTMnet; P14416; -. DR PhosphoSitePlus; P14416; -. DR SwissPalm; P14416; -. DR BioMuta; DRD2; -. DR DMDM; 118206; -. DR MassIVE; P14416; -. DR PaxDb; 9606-ENSP00000354859; -. DR PeptideAtlas; P14416; -. DR ProteomicsDB; 53055; -. [P14416-3] DR ABCD; P14416; 2 sequenced antibodies. DR Antibodypedia; 2801; 457 antibodies from 40 providers. DR DNASU; 1813; -. DR Ensembl; ENST00000346454.7; ENSP00000278597.5; ENSG00000149295.14. [P14416-2] DR Ensembl; ENST00000362072.8; ENSP00000354859.3; ENSG00000149295.14. [P14416-1] DR Ensembl; ENST00000538967.5; ENSP00000438215.1; ENSG00000149295.14. [P14416-3] DR Ensembl; ENST00000542968.5; ENSP00000442172.1; ENSG00000149295.14. [P14416-1] DR GeneID; 1813; -. DR KEGG; hsa:1813; -. DR MANE-Select; ENST00000362072.8; ENSP00000354859.3; NM_000795.4; NP_000786.1. DR UCSC; uc001pnz.4; human. [P14416-1] DR AGR; HGNC:3023; -. DR CTD; 1813; -. DR DisGeNET; 1813; -. DR GeneCards; DRD2; -. DR HGNC; HGNC:3023; DRD2. DR HPA; ENSG00000149295; Group enriched (brain, pituitary gland). DR MalaCards; DRD2; -. DR MIM; 103780; phenotype. DR MIM; 126450; gene. DR neXtProt; NX_P14416; -. DR OpenTargets; ENSG00000149295; -. DR Orphanet; 36899; Myoclonus-dystonia syndrome. DR PharmGKB; PA27478; -. DR VEuPathDB; HostDB:ENSG00000149295; -. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT00940000155539; -. DR HOGENOM; CLU_009579_11_1_1; -. DR InParanoid; P14416; -. DR OMA; APMDPLN; -. DR OrthoDB; 2999405at2759; -. DR PhylomeDB; P14416; -. DR TreeFam; TF334382; -. DR PathwayCommons; P14416; -. DR Reactome; R-HSA-390651; Dopamine receptors. DR SignaLink; P14416; -. DR SIGNOR; P14416; -. DR BioGRID-ORCS; 1813; 13 hits in 1171 CRISPR screens. DR ChiTaRS; DRD2; human. DR EvolutionaryTrace; P14416; -. DR GeneWiki; Dopamine_receptor_D2; -. DR GenomeRNAi; 1813; -. DR Pharos; P14416; Tclin. DR PRO; PR:P14416; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P14416; Protein. DR Bgee; ENSG00000149295; Expressed in putamen and 123 other cell types or tissues. DR ExpressionAtlas; P14416; baseline and differential. DR GO; GO:0001669; C:acrosomal vesicle; IEA:Ensembl. DR GO; GO:0030424; C:axon; ISS:BHF-UCL. DR GO; GO:0043679; C:axon terminus; IEA:Ensembl. DR GO; GO:0060170; C:ciliary membrane; IDA:SYSCILIA_CCNET. DR GO; GO:0005929; C:cilium; IDA:MGI. DR GO; GO:0030425; C:dendrite; ISS:BHF-UCL. DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl. DR GO; GO:0098691; C:dopaminergic synapse; IEA:Ensembl. DR GO; GO:0030139; C:endocytic vesicle; IEA:Ensembl. DR GO; GO:0097648; C:G protein-coupled receptor complex; IDA:ARUK-UCL. DR GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl. DR GO; GO:0098978; C:glutamatergic synapse; IBA:GO_Central. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016328; C:lateral plasma membrane; IEA:Ensembl. DR GO; GO:0097730; C:non-motile cilium; IDA:SYSCILIA_CCNET. DR GO; GO:0043204; C:perikaryon; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:WormBase. DR GO; GO:0045211; C:postsynaptic membrane; IEA:Ensembl. DR GO; GO:0042734; C:presynaptic membrane; IEA:Ensembl. DR GO; GO:0036126; C:sperm flagellum; IEA:Ensembl. DR GO; GO:0045202; C:synapse; IEA:GOC. DR GO; GO:0030672; C:synaptic vesicle membrane; IEA:Ensembl. DR GO; GO:0035240; F:dopamine binding; IEA:Ensembl. DR GO; GO:0001591; F:dopamine neurotransmitter receptor activity, coupled via Gi/Go; IDA:BHF-UCL. DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central. DR GO; GO:0001965; F:G-protein alpha-subunit binding; IPI:ARUK-UCL. DR GO; GO:1901363; F:heterocyclic compound binding; IEA:Ensembl. DR GO; GO:0032795; F:heterotrimeric G-protein binding; IDA:ARUK-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0035255; F:ionotropic glutamate receptor binding; IEA:Ensembl. DR GO; GO:0015459; F:potassium channel regulator activity; NAS:BHF-UCL. DR GO; GO:0046717; P:acid secretion; IEA:Ensembl. DR GO; GO:0021984; P:adenohypophysis development; ISS:BHF-UCL. DR GO; GO:0071880; P:adenylate cyclase-activating adrenergic receptor signaling pathway; IBA:GO_Central. DR GO; GO:0007195; P:adenylate cyclase-inhibiting dopamine receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0007628; P:adult walking behavior; ISS:BHF-UCL. DR GO; GO:0050482; P:arachidonic acid secretion; IDA:BHF-UCL. DR GO; GO:0008306; P:associative learning; ISS:BHF-UCL. DR GO; GO:0031223; P:auditory behavior; IEA:Ensembl. DR GO; GO:0006914; P:autophagy; IEA:Ensembl. DR GO; GO:0007409; P:axonogenesis; ISS:BHF-UCL. DR GO; GO:0048148; P:behavioral response to cocaine; ISS:BHF-UCL. DR GO; GO:0048149; P:behavioral response to ethanol; ISS:BHF-UCL. DR GO; GO:0048755; P:branching morphogenesis of a nerve; ISS:BHF-UCL. DR GO; GO:0021853; P:cerebral cortex GABAergic interneuron migration; ISS:BHF-UCL. DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:BHF-UCL. DR GO; GO:0042417; P:dopamine metabolic process; IC:BHF-UCL. DR GO; GO:0051583; P:dopamine uptake involved in synaptic transmission; IEA:Ensembl. DR GO; GO:0042756; P:drinking behavior; IEA:Ensembl. DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl. DR GO; GO:0060079; P:excitatory postsynaptic potential; NAS:ParkinsonsUK-UCL. DR GO; GO:0002031; P:G protein-coupled receptor internalization; IEA:Ensembl. DR GO; GO:0007625; P:grooming behavior; IEA:Ensembl. DR GO; GO:1990384; P:hyaloid vascular plexus regression; ISS:UniProtKB. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IC:BHF-UCL. DR GO; GO:0035556; P:intracellular signal transduction; IDA:BHF-UCL. DR GO; GO:0007626; P:locomotory behavior; ISS:BHF-UCL. DR GO; GO:0007616; P:long-term memory; IEA:Ensembl. DR GO; GO:0007194; P:negative regulation of adenylate cyclase activity; IDA:BHF-UCL. DR GO; GO:0045776; P:negative regulation of blood pressure; ISS:BHF-UCL. DR GO; GO:0030336; P:negative regulation of cell migration; ISS:BHF-UCL. DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:BHF-UCL. DR GO; GO:1900038; P:negative regulation of cellular response to hypoxia; IEA:Ensembl. DR GO; GO:0042321; P:negative regulation of circadian sleep/wake cycle, sleep; IEA:Ensembl. DR GO; GO:0051481; P:negative regulation of cytosolic calcium ion concentration; IBA:GO_Central. DR GO; GO:0060160; P:negative regulation of dopamine receptor signaling pathway; ISS:BHF-UCL. DR GO; GO:0033602; P:negative regulation of dopamine secretion; IEA:Ensembl. DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IEA:Ensembl. DR GO; GO:0045824; P:negative regulation of innate immune response; IEA:Ensembl. DR GO; GO:0046676; P:negative regulation of insulin secretion; IEA:Ensembl. DR GO; GO:2001223; P:negative regulation of neuron migration; IEA:Ensembl. DR GO; GO:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISS:BHF-UCL. DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IEA:Ensembl. DR GO; GO:0050709; P:negative regulation of protein secretion; IDA:BHF-UCL. DR GO; GO:0051967; P:negative regulation of synaptic transmission, glutamatergic; ISS:BHF-UCL. DR GO; GO:1901386; P:negative regulation of voltage-gated calcium channel activity; IDA:BHF-UCL. DR GO; GO:0001976; P:nervous system process involved in regulation of systemic arterial blood pressure; ISS:BHF-UCL. DR GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl. DR GO; GO:0007270; P:neuron-neuron synaptic transmission; ISS:BHF-UCL. DR GO; GO:0021769; P:orbitofrontal cortex development; IEA:Ensembl. DR GO; GO:0030432; P:peristalsis; ISS:BHF-UCL. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IEA:Ensembl. DR GO; GO:0060158; P:phospholipase C-activating dopamine receptor signaling pathway; IGI:MGI. DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0043473; P:pigmentation; IEA:Ensembl. DR GO; GO:0032467; P:positive regulation of cytokinesis; IMP:UniProtKB. DR GO; GO:0051586; P:positive regulation of dopamine uptake involved in synaptic transmission; ISS:BHF-UCL. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:0045745; P:positive regulation of G protein-coupled receptor signaling pathway; IEA:Ensembl. DR GO; GO:1900168; P:positive regulation of glial cell-derived neurotrophic factor production; IDA:CACAO. DR GO; GO:0060124; P:positive regulation of growth hormone secretion; ISS:BHF-UCL. DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; IEA:Ensembl. DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl. DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; ISS:BHF-UCL. DR GO; GO:0002092; P:positive regulation of receptor internalization; IEA:Ensembl. DR GO; GO:0035815; P:positive regulation of renal sodium excretion; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0035810; P:positive regulation of urine volume; IEA:Ensembl. DR GO; GO:0099170; P:postsynaptic modulation of chemical synaptic transmission; IEA:Ensembl. DR GO; GO:0060134; P:prepulse inhibition; ISS:BHF-UCL. DR GO; GO:0099171; P:presynaptic modulation of chemical synaptic transmission; IEA:Ensembl. DR GO; GO:0008104; P:protein localization; ISS:BHF-UCL. DR GO; GO:0014059; P:regulation of dopamine secretion; IBA:GO_Central. DR GO; GO:0051584; P:regulation of dopamine uptake involved in synaptic transmission; IC:BHF-UCL. DR GO; GO:0002027; P:regulation of heart rate; ISS:BHF-UCL. DR GO; GO:0090325; P:regulation of locomotion involved in locomotory behavior; IEA:Ensembl. DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; ISS:BHF-UCL. DR GO; GO:0043266; P:regulation of potassium ion transport; ISS:BHF-UCL. DR GO; GO:0002028; P:regulation of sodium ion transport; ISS:BHF-UCL. DR GO; GO:0051823; P:regulation of synapse structural plasticity; IEA:Ensembl. DR GO; GO:0032228; P:regulation of synaptic transmission, GABAergic; ISS:BHF-UCL. DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISS:BHF-UCL. DR GO; GO:0001975; P:response to amphetamine; ISS:BHF-UCL. DR GO; GO:0048678; P:response to axon injury; IEA:Ensembl. DR GO; GO:0042220; P:response to cocaine; ISS:BHF-UCL. DR GO; GO:0034776; P:response to histamine; IDA:BHF-UCL. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0014854; P:response to inactivity; IEA:Ensembl. DR GO; GO:0010039; P:response to iron ion; IEA:Ensembl. DR GO; GO:0009416; P:response to light stimulus; ISS:BHF-UCL. DR GO; GO:0043278; P:response to morphine; ISS:BHF-UCL. DR GO; GO:0035094; P:response to nicotine; IEA:Ensembl. DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; ISS:BHF-UCL. DR GO; GO:0007608; P:sensory perception of smell; ISS:BHF-UCL. DR GO; GO:0021756; P:striatum development; IEA:Ensembl. DR GO; GO:0007416; P:synapse assembly; ISS:BHF-UCL. DR GO; GO:0001659; P:temperature homeostasis; ISS:BHF-UCL. DR GO; GO:0008542; P:visual learning; ISS:BHF-UCL. DR GO; GO:0016055; P:Wnt signaling pathway; IEA:Ensembl. DR CDD; cd15309; 7tmA_D2_dopamine_R; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 2. DR InterPro; IPR001922; Dopamine_D2_rcpt. DR InterPro; IPR000929; Dopamine_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:SF87; D(2) DOPAMINE RECEPTOR; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00567; DOPAMINED2R. DR PRINTS; PR00242; DOPAMINER. 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; P14416; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Disease variant; KW Disulfide bond; G-protein coupled receptor; Glycoprotein; Golgi apparatus; KW Lipoprotein; Membrane; Palmitate; Receptor; Reference proteome; Transducer; KW Transmembrane; Transmembrane helix. FT CHAIN 1..443 FT /note="D(2) dopamine receptor" FT /id="PRO_0000069387" FT TOPO_DOM 1..37 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 38..60 FT /note="Helical; Name=1" FT /evidence="ECO:0000250" FT TOPO_DOM 61..70 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 71..93 FT /note="Helical; Name=2" FT /evidence="ECO:0000250" FT TOPO_DOM 94..108 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 109..130 FT /note="Helical; Name=3" FT /evidence="ECO:0000250" FT TOPO_DOM 131..151 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 152..172 FT /note="Helical; Name=4" FT /evidence="ECO:0000250" FT TOPO_DOM 173..188 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 189..213 FT /note="Helical; Name=5" FT /evidence="ECO:0000250" FT TOPO_DOM 214..373 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 374..395 FT /note="Helical; Name=6" FT /evidence="ECO:0000250" FT TOPO_DOM 396..409 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 410..431 FT /note="Helical; Name=7" FT /evidence="ECO:0000250" FT TOPO_DOM 432..443 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT REGION 211..373 FT /note="Interaction with PPP1R9B" FT /evidence="ECO:0000250" FT REGION 281..332 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 194 FT /note="Important for receptor activation" FT /evidence="ECO:0000250" FT SITE 197 FT /note="Important for receptor activation" FT /evidence="ECO:0000250" FT LIPID 443 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:26535572" FT CARBOHYD 5 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 17 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 23 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 107..182 FT /evidence="ECO:0000269|PubMed:29466326, FT ECO:0007744|PDB:6CM4" FT DISULFID 399..401 FT /evidence="ECO:0000269|PubMed:29466326, FT ECO:0007744|PDB:6CM4" FT VAR_SEQ 242..270 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:2531656" FT /id="VSP_001870" FT VAR_SEQ 270 FT /note="V -> VVQ (in isoform 3)" FT /evidence="ECO:0000303|PubMed:10719223" FT /id="VSP_026455" FT VARIANT 154 FT /note="V -> I (found in patients with alcohol-responsive FT myoclonus-dystonia; uncertain significance; the mutation FT does not affect functional properties; dbSNP:rs104894220)" FT /evidence="ECO:0000269|PubMed:10220438, FT ECO:0000269|PubMed:10716258" FT /id="VAR_017143" FT VARIANT 310 FT /note="P -> S (in dbSNP:rs1800496)" FT /id="VAR_014674" FT VARIANT 311 FT /note="S -> C (in dbSNP:rs1801028)" FT /evidence="ECO:0000269|PubMed:7902708" FT /id="VAR_003462" FT VARIANT 327 FT /note="K -> E (in dbSNP:rs71653614)" FT /evidence="ECO:0000269|PubMed:21179162" FT /id="VAR_064579" FT MUTAGEN 126 FT /note="C->S: No effect on palmitoylation; no effect on FT localization to the plasma membrane." FT /evidence="ECO:0000269|PubMed:26535572" FT MUTAGEN 244 FT /note="C->S: No effect on palmitoylation; no effect on FT localization to the plasma membrane." FT /evidence="ECO:0000269|PubMed:26535572" FT MUTAGEN 253 FT /note="C->S: No effect on palmitoylation; no effect on FT localization to the plasma membrane." FT /evidence="ECO:0000269|PubMed:26535572" FT MUTAGEN 443 FT /note="Missing: Decreased palmitoylation; decreased FT localization to the plasma membrane; decreased stability." FT /evidence="ECO:0000269|PubMed:26535572" FT CONFLICT 40 FT /note="L -> R (in Ref. 7; AAB26819)" FT /evidence="ECO:0000305" FT HELIX 35..61 FT /evidence="ECO:0007829|PDB:7JVR" FT HELIX 63..65 FT /evidence="ECO:0007829|PDB:6CM4" FT HELIX 68..86 FT /evidence="ECO:0007829|PDB:7JVR" FT HELIX 88..97 FT /evidence="ECO:0007829|PDB:7JVR" FT HELIX 104..137 FT /evidence="ECO:0007829|PDB:7JVR" FT HELIX 139..143 FT /evidence="ECO:0007829|PDB:7JVR" FT HELIX 145..172 FT /evidence="ECO:0007829|PDB:7JVR" FT STRAND 179..181 FT /evidence="ECO:0007829|PDB:7JVR" FT HELIX 183..185 FT /evidence="ECO:0007829|PDB:6CM4" FT HELIX 187..197 FT /evidence="ECO:0007829|PDB:7JVR" FT HELIX 199..224 FT /evidence="ECO:0007829|PDB:7JVR" FT HELIX 366..385 FT /evidence="ECO:0007829|PDB:7JVR" FT HELIX 387..399 FT /evidence="ECO:0007829|PDB:7JVR" FT HELIX 405..426 FT /evidence="ECO:0007829|PDB:7JVR" FT TURN 427..429 FT /evidence="ECO:0007829|PDB:7JVR" FT HELIX 431..442 FT /evidence="ECO:0007829|PDB:5AER" SQ SEQUENCE 443 AA; 50619 MW; 9BF8EA36C988A2E2 CRC64; MDPLNLSWYD DDLERQNWSR PFNGSDGKAD RPHYNYYATL LTLLIAVIVF GNVLVCMAVS REKALQTTTN YLIVSLAVAD LLVATLVMPW VVYLEVVGEW KFSRIHCDIF VTLDVMMCTA SILNLCAISI DRYTAVAMPM LYNTRYSSKR RVTVMISIVW VLSFTISCPL LFGLNNADQN ECIIANPAFV VYSSIVSFYV PFIVTLLVYI KIYIVLRRRR KRVNTKRSSR AFRAHLRAPL KGNCTHPEDM KLCTVIMKSN GSFPVNRRRV EAARRAQELE MEMLSSTSPP ERTRYSPIPP SHHQLTLPDP SHHGLHSTPD SPAKPEKNGH AKDHPKIAKI FEIQTMPNGK TRTSLKTMSR RKLSQQKEKK ATQMLAIVLG VFIICWLPFF ITHILNIHCD CNIPPVLYSA FTWLGYVNSA VNPIIYTTFN IEFRKAFLKI LHC //