DRD1
entrez
1812
canonical
uniprot
P21728
canonical
ensembl
ENSG00000184845
resolver
ensp
ENSP00000377353
resolver
ensp
ENSP00000620727
resolver
ensp
ENSP00000620728
resolver
enst
ENST00000393752
resolver
enst
ENST00000950668
resolver
enst
ENST00000950669
resolver
genesymbol
DRD1
resolver
hgnc
HGNC:3020
resolver
uniprot
B2RA44
resolver
uniprot
Q4QRJ0
resolver
uniprot_entry
DRD1_HUMAN
resolver
uniprot_sec
B2RA44
resolver
uniprot_sec
Q4QRJ0
resolver
activity_regulation
ACTIVITY REGULATION: 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). {ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:33571432, ECO:0000269|PubMed:33750903, ECO:0000269|PubMed:35676276, ECO:0000269|PubMed:37221270}.
uniprot
proteins
amino_acid_sequence
MRTLNTSAMDGTGLVVERDFSVRILTACFLSLLILSTLLGNTLVCAAVIRFRHLRSKVTNFFVISLAVSDLLVAVLVMPWKAVAEIAGFWPFGSFCNIWVAFDIMCSTASILNLCVISVDRYWAISSPFRYERKMTPKAAFILISVAWTLSVLISFIPVQLSWHKAKPTSPSDGNATSLAETIDNCDSSLSRTYAISSSVISFYIPVAIMIVTYTRIYRIAQKQIRRIAALERAAVHAKNCQTTTGNGKPVECSQPESSFKMSFKRETKVLKTLSVIMGVFVCCWLPFFILNCILPFCGSGETQPFCIDSNTFDVFVWFGWANSSLNPIIYAFNADFRKAFSTLLGCYRLCPATNNAIETVSINNNGAAMFSSHHEPRGSISKECNLVYLIPHAVGSSEDLKKEEAAGIARPLEKLSPALSVILDYDTDVSLEKIQPITQNGQHPT
uniprot
proteins
function
FUNCTION: 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). {ECO:0000250|UniProtKB:Q61616, ECO:0000269|PubMed:11500503, ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:33571432, ECO:0000269|PubMed:33750903, ECO:0000269|PubMed:34083522, ECO:0000269|PubMed:35676276, ECO:0000269|PubMed:35687690, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39094559, ECO:0000269|PubMed:7782330}.
uniprot
proteins
mass_dalton
49293
uniprot
proteins
mutagenesis
MUTAGEN 81; /note="K->A: Decreased dopamine-binding and G protein-coupled receptor signaling. Decreased activation by SKF81297 and SKF83959 small-molecule agonists. Does not affect activation by rotigotine."; /evidence="ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:35676276, ECO:0000269|PubMed:37221270"; MUTAGEN 103; /note="D->A,N,L: Abolished dopamine-binding and G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:33571432, ECO:0000269|PubMed:33750903, ECO:0000269|PubMed:35676276, ECO:0000269|PubMed:35687690"; MUTAGEN 104; /note="I->A: Decreased dopamine-binding and G protein-coupled receptor signaling. Decreased binding of SCH23390 antagonist."; /evidence="ECO:0000269|PubMed:33571431"; MUTAGEN 107; /note="S->A: Decreased dopamine-binding and G protein-coupled receptor signaling. Decreased activation by SKF81297 and SKF83959 small-molecule agonists."; /evidence="ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:35687690"; MUTAGEN 108; /note="T->A: Decreased dopamine-binding and G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35687690, ECO:0000269|PubMed:37221270"; MUTAGEN 123; /note="W->F: Abolished ability of LY3154207 to act as a positivie allosteric modulator."; /evidence="ECO:0000269|PubMed:33571432"; MUTAGEN 130; /note="R->Q: Abolished ability of LY3154207 to act as a positivie allosteric modulator."; /evidence="ECO:0000269|PubMed:33571432"; MUTAGEN 190; /note="L->A: Decreased dopamine-binding and G protein-coupled receptor signaling. Decreased binding of SCH23390 antagonist. Decreased activation by SKF81297 and SKF83959 small-molecule agonists."; /evidence="ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:35676276, ECO:0000269|PubMed:35687690"; MUTAGEN 198; /note="S->A: Abolished dopamine-binding and G protein-coupled receptor signaling. Decreased binding of SCH23390 antagonist."; /evidence="ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:33571432, ECO:0000269|PubMed:33750903, ECO:0000269|PubMed:35676276, ECO:0000269|PubMed:35687690"; MUTAGEN 198; /note="S->G: Decreased affinity for dopamine."; /evidence="ECO:0000269|PubMed:35676276, ECO:0000269|PubMed:37221270"; MUTAGEN 202; /note="S->A: Abolished dopamine-binding and G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:33571432, ECO:0000269|PubMed:35687690, ECO:0000269|PubMed:37221270"; MUTAGEN 225; /note="I->A: Decreased dopamine-binding and G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35687690"; MUTAGEN 288; /note="F->A: Decreased dopamine-binding and G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:33750903, ECO:0000269|PubMed:35676276"; MUTAGEN 292; /note="N->A: Decreased dopamine-binding and G protein-coupled receptor signaling. Decreased binding of SCH23390 antagonist."; /evidence="ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:33750903, ECO:0000269|PubMed:37221270"; MUTAGEN 321; /note="W->A: Decreased dopamine-binding and G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:33750903"; MUTAGEN 381..395; /note="Missing: Reduced localization to ciliary membrane."; /evidence="ECO:0000269|PubMed:26182404"; MUTAGEN 397..398; /note="SS->AA: Decreased phosphorylation by PKC; when associated with A-417--421-A."; /evidence="ECO:0000269|PubMed:20969574"; MUTAGEN 417..421; /note="SPALS->APALA: Decreased phosphorylation by PKC; when associated with A-397-398-A."; /evidence="ECO:0000269|PubMed:20969574"; MUTAGEN 428..431; /note="TDVS->VDVA: Decreased constitutive phosphorylation by GRK4."; /evidence="ECO:0000269|PubMed:16338988
uniprot
proteins
post_translational_modification
PTM: 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). {ECO:0000250|UniProtKB:P18901, ECO:0000269|PubMed:16338988, ECO:0000269|PubMed:20969574}.
uniprot
proteins
protein_family
G protein-coupled receptor 1 family
uniprot
proteins
pubmed
10618483
uniprot
proteins
pubmed
11500503
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16338988
uniprot
proteins
pubmed
1975640
uniprot
proteins
pubmed
20969574
uniprot
proteins
pubmed
21179162
uniprot
proteins
pubmed
2144334
uniprot
proteins
pubmed
2168520
uniprot
proteins
pubmed
23936473
uniprot
proteins
pubmed
24040266
uniprot
proteins
pubmed
26182404
uniprot
proteins
pubmed
33571431
uniprot
proteins
pubmed
33571432
uniprot
proteins
pubmed
33750903
uniprot
proteins
pubmed
34083522
uniprot
proteins
pubmed
35676276
uniprot
proteins
pubmed
35687690
uniprot
proteins
pubmed
37221270
uniprot
proteins
pubmed
39094559
uniprot
proteins
pubmed
7782330
uniprot
proteins
pubmed
8471124
uniprot
proteins
sequence_length
446
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Postsynaptic cell membrane {ECO:0000269|PubMed:24040266}; Multi-pass membrane protein {ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:33571432}. Cell projection, dendritic spine membrane {ECO:0000250|UniProtKB:Q61616}; Multi-pass membrane protein {ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:33571432}. Cell projection, cilium membrane {ECO:0000269|PubMed:23936473, ECO:0000269|PubMed:26182404}; Multi-pass membrane protein {ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:33571432}. Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P18901}; Multi-pass membrane protein {ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:33571432}. Note=Transport from the endoplasmic reticulum to the cell surface is regulated by interaction with DNAJC14. {ECO:0000250|UniProtKB:P18901}.
uniprot
proteins
transmembrane_region
TRANSMEM 24..46; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:33571432, ECO:0000269|PubMed:33750903, ECO:0000269|PubMed:34083522, ECO:0000269|PubMed:35676276, ECO:0000269|PubMed:35687690, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39094559, ECO:0007744|PDB:7CKW, ECO:0007744|PDB:7CKX, ECO:0007744|PDB:7CKZ, ECO:0007744|PDB:7CRH, ECO:0007744|PDB:7F0T, ECO:0007744|PDB:7F1O, ECO:0007744|PDB:7F1Z, ECO:0007744|PDB:7F23, ECO:0007744|PDB:7F24, ECO:0007744|PDB:7JOZ, ECO:0007744|PDB:7JV5, ECO:0007744|PDB:7JVP, ECO:0007744|PDB:7JVQ, ECO:0007744|PDB:7LJC, ECO:0007744|PDB:7LJD, ECO:0007744|PDB:7X2C, ECO:0007744|PDB:7X2D, ECO:0007744|PDB:7X2F, ECO:0007744|PDB:8IRR, ECO:0007744|PDB:8JXR, ECO:0007744|PDB:8JXS"; TRANSMEM 62..83; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:33571432, ECO:0000269|PubMed:33750903, ECO:0000269|PubMed:34083522, ECO:0000269|PubMed:35676276, ECO:0000269|PubMed:35687690, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39094559, ECO:0007744|PDB:7CKW, ECO:0007744|PDB:7CKX, ECO:0007744|PDB:7CKZ, ECO:0007744|PDB:7CRH, ECO:0007744|PDB:7F0T, ECO:0007744|PDB:7F1O, ECO:0007744|PDB:7F1Z, ECO:0007744|PDB:7F23, ECO:0007744|PDB:7F24, ECO:0007744|PDB:7JOZ, ECO:0007744|PDB:7JV5, ECO:0007744|PDB:7JVP, ECO:0007744|PDB:7JVQ, ECO:0007744|PDB:7LJC, ECO:0007744|PDB:7LJD, ECO:0007744|PDB:7X2C, ECO:0007744|PDB:7X2D, ECO:0007744|PDB:7X2F, ECO:0007744|PDB:8IRR, ECO:0007744|PDB:8JXR, ECO:0007744|PDB:8JXS"; TRANSMEM 97..119; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:33571432, ECO:0000269|PubMed:33750903, ECO:0000269|PubMed:34083522, ECO:0000269|PubMed:35676276, ECO:0000269|PubMed:35687690, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39094559, ECO:0007744|PDB:7CKW, ECO:0007744|PDB:7CKX, ECO:0007744|PDB:7CKZ, ECO:0007744|PDB:7CRH, ECO:0007744|PDB:7F0T, ECO:0007744|PDB:7F1O, ECO:0007744|PDB:7F1Z, ECO:0007744|PDB:7F23, ECO:0007744|PDB:7F24, ECO:0007744|PDB:7JOZ, ECO:0007744|PDB:7JV5, ECO:0007744|PDB:7JVP, ECO:0007744|PDB:7JVQ, ECO:0007744|PDB:7LJC, ECO:0007744|PDB:7LJD, ECO:0007744|PDB:7X2C, ECO:0007744|PDB:7X2D, ECO:0007744|PDB:7X2F, ECO:0007744|PDB:8IRR, ECO:0007744|PDB:8JXR, ECO:0007744|PDB:8JXS"; TRANSMEM 140..161; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:33571432, ECO:0000269|PubMed:33750903, ECO:0000269|PubMed:34083522, ECO:0000269|PubMed:35676276, ECO:0000269|PubMed:35687690, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39094559, ECO:0007744|PDB:7CKW, ECO:0007744|PDB:7CKX, ECO:0007744|PDB:7CKZ, ECO:0007744|PDB:7CRH, ECO:0007744|PDB:7F0T, ECO:0007744|PDB:7F1O, ECO:0007744|PDB:7F1Z, ECO:0007744|PDB:7F23, ECO:0007744|PDB:7F24, ECO:0007744|PDB:7JOZ, ECO:0007744|PDB:7JV5, ECO:0007744|PDB:7JVP, ECO:0007744|PDB:7JVQ, ECO:0007744|PDB:7LJC, ECO:0007744|PDB:7LJD, ECO:0007744|PDB:7X2C, ECO:0007744|PDB:7X2D, ECO:0007744|PDB:7X2F, ECO:0007744|PDB:8IRR, ECO:0007744|PDB:8JXR, ECO:0007744|PDB:8JXS"; TRANSMEM 193..215; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:33571432, ECO:0000269|PubMed:33750903, ECO:0000269|PubMed:34083522, ECO:0000269|PubMed:35676276, ECO:0000269|PubMed:35687690, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39094559, ECO:0007744|PDB:7CKW, ECO:0007744|PDB:7CKX, ECO:0007744|PDB:7CKZ, ECO:0007744|PDB:7CRH, ECO:0007744|PDB:7F0T, ECO:0007744|PDB:7F1O, ECO:0007744|PDB:7F1Z, ECO:0007744|PDB:7F23, ECO:0007744|PDB:7F24, ECO:0007744|PDB:7JOZ, ECO:0007744|PDB:7JV5, ECO:0007744|PDB:7JVP, ECO:0007744|PDB:7JVQ, ECO:0007744|PDB:7LJC, ECO:0007744|PDB:7LJD, ECO:0007744|PDB:7X2C, ECO:0007744|PDB:7X2D, ECO:0007744|PDB:7X2F, ECO:0007744|PDB:8IRR, ECO:0007744|PDB:8JXR, ECO:0007744|PDB:8JXS"; TRANSMEM 273..294; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:33571432, ECO:0000269|PubMed:33750903, ECO:0000269|PubMed:34083522, ECO:0000269|PubMed:35676276, ECO:0000269|PubMed:35687690, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39094559, ECO:0007744|PDB:7CKW, ECO:0007744|PDB:7CKX, ECO:0007744|PDB:7CKZ, ECO:0007744|PDB:7CRH, ECO:0007744|PDB:7F0T, ECO:0007744|PDB:7F1O, ECO:0007744|PDB:7F1Z, ECO:0007744|PDB:7F23, ECO:0007744|PDB:7F24, ECO:0007744|PDB:7JOZ, ECO:0007744|PDB:7JV5, ECO:0007744|PDB:7JVP, ECO:0007744|PDB:7JVQ, ECO:0007744|PDB:7LJC, ECO:0007744|PDB:7LJD, ECO:0007744|PDB:7X2C, ECO:0007744|PDB:7X2D, ECO:0007744|PDB:7X2F, ECO:0007744|PDB:8IRR, ECO:0007744|PDB:8JXR, ECO:0007744|PDB:8JXS"; TRANSMEM 311..333; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:33571432, ECO:0000269|PubMed:33750903, ECO:0000269|PubMed:34083522, ECO:0000269|PubMed:35676276, ECO:0000269|PubMed:35687690, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39094559, ECO:0007744|PDB:7CKW, ECO:0007744|PDB:7CKX, ECO:0007744|PDB:7CKZ, ECO:0007744|PDB:7CRH, ECO:0007744|PDB:7F0T, ECO:0007744|PDB:7F1O, ECO:0007744|PDB:7F1Z, ECO:0007744|PDB:7F23, ECO:0007744|PDB:7F24, ECO:0007744|PDB:7JOZ, ECO:0007744|PDB:7JV5, ECO:0007744|PDB:7JVP, ECO:0007744|PDB:7JVQ, ECO:0007744|PDB:7LJC, ECO:0007744|PDB:7LJD, ECO:0007744|PDB:7X2C, ECO:0007744|PDB:7X2D, ECO:0007744|PDB:7X2F, ECO:0007744|PDB:8IRR, ECO:0007744|PDB:8JXR, ECO:0007744|PDB:8JXS
uniprot
proteins