{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P21728","secondaryAccessions":["B2RA44","Q4QRJ0"],"uniProtkbId":"DRD1_HUMAN","entryAudit":{"firstPublicDate":"1991-05-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1991-05-01","entryVersion":234,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Dopamine receptor D1"}},"alternativeNames":[{"fullName":{"value":"D(1A) dopamine receptor"}},{"fullName":{"value":"Dopamine D1 receptor"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"33571432"},{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:3020"}],"value":"DRD1"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q61616"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11500503"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33571431"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33571432"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33750903"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34083522"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35676276"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35687690"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37221270"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"39094559"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7782330"}],"value":"G protein-coupled receptor for dopamine, a catecholamine neurotransmitter hormone that functions as the brain's 'reward chemical', driving motivation, reinforcement learning and pleasure (PubMed:11500503, PubMed:33571431, PubMed:33571432, PubMed:33750903, PubMed:34083522, PubMed:35676276, PubMed:35687690, PubMed:37221270). Dopamine binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:33571431, PubMed:33571432, PubMed:33750903, PubMed:34083522, PubMed:35676276, PubMed:35687690). Dopamine receptors can be classified in two categories: (1) DRD1 (together with DRD5) is a D1-type receptor and is coupled to G(s) G proteins, mediating activation of adenylate cyclase activity, while D2-type receptors (DRD2, DRD3 and DRD4) are coupled to G(i)/G(o) G proteins and promote inhibition of adenylate cyclase activity (PubMed:33571431, PubMed:33571432, PubMed:33750903, PubMed:34083522, PubMed:35676276, PubMed:35687690, PubMed:7782330). D1- and D2-type dopamine receptors have antagonistic effects, particularly in the brain's striatum, where they govern voluntary movement and reward: D1-type receptors generally stimulate neural activity and promotes action, while D2-type receptors tend to inhibit neural activity and suppress movement (By similarity). DRD1 acts as an essential regulator of reward, motor activity and cognition in the central nervous system and play beneficial roles in peripheral tissues including inhibiting inflammatory reactions and maintaining cardiovascular and kidney homeostasis (PubMed:33571431, PubMed:33571432). DRD1 and DRD2 are the most abundant dopamine receptors in the central nervous system, especially in the basal ganglia and the prefrontal cortex (PubMed:33571431, PubMed:33571432). DRD1 can also couple with G(q) by forming a heteromer with the ghrelin receptor GHSR in hippocampal neurons independently of ghrelin (By similarity). Following DRD1 activation by dopamine, GHSR acts as a coreceptor promoting DRD1 coupling to G(q) at the expense of G(s), initiating hippocampal synaptic plasticity involved in memory and learning (By similarity). Forms heterotetramers with DRD3 to potentiate beta-arrestin recruitment and mediate locomotor activity (By similarity). Also acts as a receptor for D-lysergic (LSD) psychedelic drug (PubMed:39094559)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33571431"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33571432"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33750903"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35676276"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37221270"}],"value":"Activated by a number of small-molecule agonists, such as apomorphine, fenoldopam, tavapadon, A77636, SKF81297 and SKF83959, or non-catechol G(s)- biased agonist PW0464 (PubMed:33571431, PubMed:33571432). Activated by the pan-agonist rotigotine, which activates all five dopamine receptors (PubMed:37221270). Inhibited by small-molecule antagonist SCH23390 (PubMed:33571431). Allosterically activated by LY3154207 (PubMed:33571432, PubMed:33750903, PubMed:35676276)"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P18901"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q61616"}],"value":"Interacts with DNAJC14 via its C-terminus (By similarity). Interacts with DORIP1 (By similarity). Interacts with DRD2 (By similarity). Interacts with DRD3 (By similarity). Interacts with GHSR; forms a heteromer with GHSR in hippocampal neurons (By similarity)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P21728","intActId":"EBI-6624459"},"interactantTwo":{"uniProtKBAccession":"Q92993","geneName":"KAT5","intActId":"EBI-399080"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P21728","intActId":"EBI-6624459"},"interactantTwo":{"uniProtKBAccession":"Q8TAP4-4","geneName":"LMO3","intActId":"EBI-11742507"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P21728","intActId":"EBI-6624459"},"interactantTwo":{"uniProtKBAccession":"P17252","geneName":"PRKCA","intActId":"EBI-1383528"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P21728","intActId":"EBI-6624459"},"interactantTwo":{"uniProtKBAccession":"O60894","geneName":"RAMP1","intActId":"EBI-962893"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P21728","intActId":"EBI-6624459"},"interactantTwo":{"uniProtKBAccession":"Q15047-2","geneName":"SETDB1","intActId":"EBI-9090795"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P21728","intActId":"EBI-6624459"},"interactantTwo":{"uniProtKBAccession":"P61981","geneName":"YWHAG","intActId":"EBI-359832"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P18901"}],"value":"Transport from the endoplasmic reticulum to the cell surface is regulated by interaction with DNAJC14"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24040266"}],"value":"Postsynaptic cell membrane","id":"SL-0219"},"topology":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33571431"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33571432"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q61616"}],"value":"Cell projection, dendritic spine membrane","id":"SL-0285"},"topology":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33571431"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33571432"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23936473"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26182404"}],"value":"Cell projection, cilium membrane","id":"SL-0305"},"topology":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33571431"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33571432"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P18901"}],"value":"Endoplasmic reticulum membrane","id":"SL-0097"},"topology":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33571431"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33571432"}],"value":"Multi-pass membrane protein","id":"SL-9909"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"2144334"}],"value":"Detected in caudate, nucleus accumbens and in the olfactory tubercle"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P18901"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16338988"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20969574"}],"value":"Phosphorylated at Ser-258 and Ser-259 by GRK2 and GRK3 following prolonged stimulation by dopamine, promoting association with beta-arrestin (ARRB1 or ARRB2), leading to receptor desensitization and negative regulation of G protein-coupled receptor signaling (By similarity). Phosphorylated at Thr-428 and Ser-431 by GRK4 in the absence of dopamine activation, resulting in constitutive desensitization (PubMed:16338988). Constitutive phosphorylation (in absence of dopamine activation) by some isoforms of PKC (PRKCA, PRKCB, PRKCE and PRKCG) inhibits G protein-coupled receptor signaling (PubMed:20969574)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00521"}],"value":"Belongs to the G protein-coupled receptor 1 family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":446,"modifier":"EXACT"}},"description":"Dopamine receptor D1","featureId":"PRO_0000069373"},{"type":"Topological 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