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P61169

- DRD2_RAT

UniProt

P61169 - DRD2_RAT

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Protein

D(2) dopamine receptor

Gene
Drd2
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei114 – 1141Agonist By similarity
Sitei194 – 1941Important for receptor activation
Sitei197 – 1971Important for receptor activation

GO - Molecular functioni

  1. dopamine binding Source: RGD
  2. dopamine neurotransmitter receptor activity Source: RGD
  3. dopamine neurotransmitter receptor activity, coupled via Gi/Go Source: BHF-UCL
  4. drug binding Source: BHF-UCL
  5. ionotropic glutamate receptor binding Source: RGD
  6. protein binding Source: IntAct
  7. protein heterodimerization activity Source: RGD
  8. protein homodimerization activity Source: RGD
  9. receptor binding Source: RGD

GO - Biological processi

  1. acid secretion Source: BHF-UCL
  2. activation of protein kinase activity Source: RGD
  3. adenohypophysis development Source: Ensembl
  4. adenylate cyclase-inhibiting dopamine receptor signaling pathway Source: BHF-UCL
  5. adenylate cyclase-modulating G-protein coupled receptor signaling pathway Source: RGD
  6. adult walking behavior Source: Ensembl
  7. arachidonic acid secretion Source: Ensembl
  8. auditory behavior Source: RGD
  9. axonogenesis Source: Ensembl
  10. behavioral response to cocaine Source: Ensembl
  11. behavioral response to ethanol Source: Ensembl
  12. branching morphogenesis of a nerve Source: Ensembl
  13. cellular potassium ion homeostasis Source: BHF-UCL
  14. cerebral cortex GABAergic interneuron migration Source: Ensembl
  15. circadian regulation of gene expression Source: Ensembl
  16. dopamine metabolic process Source: Ensembl
  17. dopamine receptor signaling pathway Source: RGD
  18. feeding behavior Source: Ensembl
  19. forebrain development Source: RGD
  20. G-protein coupled receptor internalization Source: RGD
  21. grooming behavior Source: Ensembl
  22. intracellular signal transduction Source: Ensembl
  23. locomotory behavior Source: RGD
  24. long-term memory Source: RGD
  25. negative regulation of adenylate cyclase activity Source: BHF-UCL
  26. negative regulation of blood pressure Source: Ensembl
  27. negative regulation of cell migration Source: Ensembl
  28. negative regulation of cell proliferation Source: Ensembl
  29. negative regulation of circadian sleep/wake cycle, sleep Source: RGD
  30. negative regulation of cytosolic calcium ion concentration Source: RGD
  31. negative regulation of dopamine receptor signaling pathway Source: Ensembl
  32. negative regulation of dopamine secretion Source: RGD
  33. negative regulation of insulin secretion Source: RGD
  34. negative regulation of protein kinase B signaling Source: Ensembl
  35. negative regulation of protein secretion Source: Ensembl
  36. negative regulation of synaptic transmission, glutamatergic Source: Ensembl
  37. negative regulation of voltage-gated calcium channel activity Source: BHF-UCL
  38. neurological system process involved in regulation of systemic arterial blood pressure Source: Ensembl
  39. orbitofrontal cortex development Source: RGD
  40. peristalsis Source: Ensembl
  41. phosphatidylinositol metabolic process Source: BHF-UCL
  42. phospholipase C-activating dopamine receptor signaling pathway Source: Ensembl
  43. pigmentation Source: Ensembl
  44. positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway Source: Ensembl
  45. positive regulation of dopamine uptake involved in synaptic transmission Source: Ensembl
  46. positive regulation of ERK1 and ERK2 cascade Source: RGD
  47. positive regulation of G-protein coupled receptor protein signaling pathway Source: RGD
  48. positive regulation of growth hormone secretion Source: Ensembl
  49. positive regulation of long-term synaptic potentiation Source: RGD
  50. positive regulation of mitosis Source: BHF-UCL
  51. positive regulation of multicellular organism growth Source: Ensembl
  52. positive regulation of neuroblast proliferation Source: Ensembl
  53. positive regulation of receptor internalization Source: RGD
  54. positive regulation of renal sodium excretion Source: Ensembl
  55. positive regulation of transcription from RNA polymerase II promoter Source: RGD
  56. positive regulation of urine volume Source: Ensembl
  57. prepulse inhibition Source: Ensembl
  58. protein localization Source: Ensembl
  59. regulation of heart rate Source: Ensembl
  60. regulation of locomotion involved in locomotory behavior Source: RGD
  61. regulation of long-term neuronal synaptic plasticity Source: Ensembl
  62. regulation of MAPK cascade Source: RGD
  63. regulation of phosphoprotein phosphatase activity Source: RGD
  64. regulation of potassium ion transport Source: BHF-UCL
  65. regulation of sodium ion transport Source: Ensembl
  66. regulation of synapse structural plasticity Source: RGD
  67. regulation of synaptic transmission Source: RGD
  68. regulation of synaptic transmission, GABAergic Source: Ensembl
  69. release of sequestered calcium ion into cytosol Source: BHF-UCL
  70. response to amphetamine Source: RGD
  71. response to axon injury Source: RGD
  72. response to drug Source: BHF-UCL
  73. response to ethanol Source: RGD
  74. response to histamine Source: Ensembl
  75. response to hypoxia Source: RGD
  76. response to inactivity Source: RGD
  77. response to iron ion Source: RGD
  78. response to morphine Source: Ensembl
  79. response to nicotine Source: RGD
  80. response to toxic substance Source: RGD
  81. sensory perception of smell Source: Ensembl
  82. striatum development Source: RGD
  83. synapse assembly Source: BHF-UCL
  84. synaptic transmission, dopaminergic Source: RGD
  85. temperature homeostasis Source: Ensembl
  86. visual learning Source: Ensembl
  87. Wnt signaling pathway Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Names & Taxonomyi

Protein namesi
Recommended name:
D(2) dopamine receptor
Alternative name(s):
Dopamine D2 receptor
Gene namesi
Name:Drd2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 8

Organism-specific databases

RGDi2520. Drd2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3737Extracellular By similarityAdd
BLAST
Transmembranei38 – 6023Helical; Name=1; By similarityAdd
BLAST
Topological domaini61 – 7010Cytoplasmic By similarity
Transmembranei71 – 9323Helical; Name=2; By similarityAdd
BLAST
Topological domaini94 – 10815Extracellular By similarityAdd
BLAST
Transmembranei109 – 13022Helical; Name=3; By similarityAdd
BLAST
Topological domaini131 – 15121Cytoplasmic By similarityAdd
BLAST
Transmembranei152 – 17221Helical; Name=4; By similarityAdd
BLAST
Topological domaini173 – 18816Extracellular By similarityAdd
BLAST
Transmembranei189 – 21325Helical; Name=5; By similarityAdd
BLAST
Topological domaini214 – 374161Cytoplasmic By similarityAdd
BLAST
Transmembranei375 – 39622Helical; Name=6; By similarityAdd
BLAST
Topological domaini397 – 41014Extracellular By similarityAdd
BLAST
Transmembranei411 – 43222Helical; Name=7; By similarityAdd
BLAST
Topological domaini433 – 44412Cytoplasmic By similarityAdd
BLAST

GO - Cellular componenti

  1. acrosomal vesicle Source: RGD
  2. axon Source: RGD
  3. axon terminus Source: RGD
  4. cytoplasmic vesicle Source: RGD
  5. dendrite Source: RGD
  6. dendritic spine Source: RGD
  7. endocytic vesicle Source: RGD
  8. integral component of plasma membrane Source: InterPro
  9. lateral plasma membrane Source: RGD
  10. membrane Source: BHF-UCL
  11. perikaryon Source: RGD
  12. plasma membrane Source: RGD
  13. postsynaptic density Source: RGD
  14. sperm flagellum Source: RGD
  15. synaptic vesicle membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi193 – 1931S → A: Moderate decrease in ligand binding. 200-fold reduction of agonist-mediated cAMP inhibition. 1 Publication
Mutagenesisi194 – 1941S → A: Small decrease in agonist binding. Complete loss of agonist-mediated cAMP inhibition. 1 Publication
Mutagenesisi197 – 1971S → A: Small decrease in agonist binding. 18-fold reduction of agonist-mediated cAMP inhibition. 1 Publication
Mutagenesisi420 – 4201S → A: Moderate decrease in ligand binding. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 444444D(2) dopamine receptorPRO_0000069390Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi5 – 51N-linked (GlcNAc...) Reviewed prediction
Glycosylationi17 – 171N-linked (GlcNAc...) Reviewed prediction
Glycosylationi23 – 231N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi107 ↔ 182 By similarity
Disulfide bondi400 ↔ 402 By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PRIDEiP61169.

PTM databases

PhosphoSiteiP61169.

Expressioni

Gene expression databases

GenevestigatoriP61169.

Interactioni

Subunit structurei

Forms homo- and heterooligomers with DRD4. The interaction with DRD4 may modulate agonist-induced downstream signaling By similarity. Interacts with HTR2A, GNAI1, CADPS and CADPS2 By similarity. Interacts with GPRASP1, PPP1R9B and CLIC6. Interacts with ARRB2.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Ppp1r9bO352742EBI-80012,EBI-80022

Protein-protein interaction databases

BioGridi246498. 2 interactions.
DIPiDIP-30883N.
IntActiP61169. 3 interactions.
MINTiMINT-4792453.

Structurei

3D structure databases

ProteinModelPortaliP61169.
SMRiP61169. Positions 37-444.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni190 – 1978Agonist binding By similarity
Regioni211 – 374164Interaction with PPP1R9BAdd
BLAST
Regioni387 – 3959Agonist binding By similarity

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG309657.
GeneTreeiENSGT00750000117240.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP61169.
KOiK04145.
OMAiNSVKHSR.
OrthoDBiEOG769ZMG.
PhylomeDBiP61169.
TreeFamiTF334382.

Family and domain databases

Gene3Di1.20.1070.10. 2 hits.
InterProiIPR001922. Dopamine_D2_rcpt.
IPR000929. Dopamine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00567. DOPAMINED2R.
PR00242. DOPAMINER.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform Long (identifier: P61169-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

MDPLNLSWYD DDLERQNWSR PFNGSEGKAD RPHYNYYAML LTLLIFIIVF    50
GNVLVCMAVS REKALQTTTN YLIVSLAVAD LLVATLVMPW VVYLEVVGEW 100
KFSRIHCDIF VTLDVMMCTA SILNLCAISI DRYTAVAMPM LYNTRYSSKR 150
RVTVMIAIVW VLSFTISCPL LFGLNNTDQN ECIIANPAFV VYSSIVSFYV 200
PFIVTLLVYI KIYIVLRKRR KRVNTKRSSR AFRANLKTPL KGNCTHPEDM 250
KLCTVIMKSN GSFPVNRRRM DAARRAQELE MEMLSSTSPP ERTRYSPIPP 300
SHHQLTLPDP SHHGLHSNPD SPAKPEKNGH AKIVNPRIAK FFEIQTMPNG 350
KTRTSLKTMS RRKLSQQKEK KATQMLAIVL GVFIICWLPF FITHILNIHC 400
DCNIPPVLYS AFTWLGYVNS AVNPIIYTTF NIEFRKAFMK ILHC 444
Length:444
Mass (Da):50,904
Last modified:May 10, 2004 - v1
Checksum:i216E56CEE5CA32FB
GO
Isoform Short (identifier: P61169-2) [UniParc] [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     242-270: Missing.

Show »
Length:415
Mass (Da):47,599
Checksum:i2923089F3EDAC911
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei242 – 27029Missing in isoform Short. VSP_001871Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti99 – 991E → D in CAA37373. 1 Publication
Sequence conflicti173 – 1731G → R in CAA37373. 1 Publication
Sequence conflicti180 – 1801N → G in CAA37373. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M36831 mRNA. Translation: AAA41075.1.
X53278 mRNA. Translation: CAA37373.1.
X56065 mRNA. Translation: CAA39543.1.
M32241 mRNA. Translation: AAA41074.1.
PIRiS08146.
RefSeqiNP_036679.1. NM_012547.1. [P61169-1]
XP_006243041.1. XM_006242979.1. [P61169-2]
UniGeneiRn.87299.

Genome annotation databases

EnsembliENSRNOT00000045944; ENSRNOP00000043759; ENSRNOG00000008428. [P61169-2]
GeneIDi24318.
KEGGirno:24318.
UCSCiRGD:2520. rat.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M36831 mRNA. Translation: AAA41075.1 .
X53278 mRNA. Translation: CAA37373.1 .
X56065 mRNA. Translation: CAA39543.1 .
M32241 mRNA. Translation: AAA41074.1 .
PIRi S08146.
RefSeqi NP_036679.1. NM_012547.1. [P61169-1 ]
XP_006243041.1. XM_006242979.1. [P61169-2 ]
UniGenei Rn.87299.

3D structure databases

ProteinModelPortali P61169.
SMRi P61169. Positions 37-444.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 246498. 2 interactions.
DIPi DIP-30883N.
IntActi P61169. 3 interactions.
MINTi MINT-4792453.

Chemistry

BindingDBi P61169.
ChEMBLi CHEMBL2111342.
GuidetoPHARMACOLOGYi 215.

Protein family/group databases

GPCRDBi Search...

PTM databases

PhosphoSitei P61169.

Proteomic databases

PRIDEi P61169.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000045944 ; ENSRNOP00000043759 ; ENSRNOG00000008428 . [P61169-2 ]
GeneIDi 24318.
KEGGi rno:24318.
UCSCi RGD:2520. rat.

Organism-specific databases

CTDi 1813.
RGDi 2520. Drd2.

Phylogenomic databases

eggNOGi NOG309657.
GeneTreei ENSGT00750000117240.
HOGENOMi HOG000239242.
HOVERGENi HBG106962.
InParanoidi P61169.
KOi K04145.
OMAi NSVKHSR.
OrthoDBi EOG769ZMG.
PhylomeDBi P61169.
TreeFami TF334382.

Miscellaneous databases

NextBioi 284001.
PROi P61169.

Gene expression databases

Genevestigatori P61169.

Family and domain databases

Gene3Di 1.20.1070.10. 2 hits.
InterProi IPR001922. Dopamine_D2_rcpt.
IPR000929. Dopamine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view ]
Pfami PF00001. 7tm_1. 1 hit.
[Graphical view ]
PRINTSi PR00567. DOPAMINED2R.
PR00242. DOPAMINER.
PR00237. GPCRRHODOPSN.
PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
    Tissue: Brain.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Alternative splicing directs the expression of two D2 dopamine receptor isoforms."
    Giros B., Sokoloff P., Martres M.-P., Riou J.-F., Emorine L.J., Schwartz J.-C.
    Nature 342:923-926(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. "Multiple D2 dopamine receptors produced by alternative RNA splicing."
    Monsma F.J. Jr., McVittie L.D., Gerfen C.R., Mahan L.C., Sibley D.R.
    Nature 342:926-929(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  5. "Two forms of the rat D2 dopamine receptor as revealed by the polymerase chain reaction."
    Rao D.D., McKelvy J., Kebabian J., MacKenzie R.G.
    FEBS Lett. 263:18-22(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  6. "5'untranslated region of rat pituitary dopamine D2(B) receptor contains a putative CpG island."
    Taylor P.L., Inglis J.D., Eidne K.A.
    Submitted (OCT-1990) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
    Strain: Sprague-Dawley.
  7. "Identification by sequence analysis of a second rat brain cDNA encoding the dopamine (D2) receptor."
    Miller J.C., Wang Y., Filer D.
    Biochem. Biophys. Res. Commun. 166:109-112(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 242-270.
  8. "Cloning of two additional catecholamine receptors from rat brain."
    O'Dowd B.F., Nguyen T., Tirpak A., Jarvie K.R., Israel Y., Seeman P., Niznik H.B.
    FEBS Lett. 262:8-12(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 242-270.
  9. "Contributions of conserved serine residues to the interactions of ligands with dopamine D2 receptors."
    Cox B.A., Henningsen R.A., Spanoyannis A., Neve R.L., Neve K.A.
    J. Neurochem. 59:627-635(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF SER-193; SER-194; SER-197 AND SER-420.
  10. "Association of the D2 dopamine receptor third cytoplasmic loop with spinophilin, a protein phosphatase-1-interacting protein."
    Smith F.D., Oxford G.S., Milgram S.L.
    J. Biol. Chem. 274:19894-19900(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PPP1R9B.
  11. "CLIC6, a member of the intracellular chloride channel family, interacts with dopamine D(2)-like receptors."
    Griffon N., Jeanneteau F., Prieur F., Diaz J., Sokoloff P.
    Brain Res. Mol. Brain Res. 117:47-57(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CLIC6.
  12. Cited for: INTERACTION WITH GPRASP1.
  13. "G protein-coupled receptor kinase-mediated phosphorylation regulates post-endocytic trafficking of the D2 dopamine receptor."
    Namkung Y., Dipace C., Javitch J.A., Sibley D.R.
    J. Biol. Chem. 284:15038-15051(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ARRB2.
  14. "Molecular modelling of D2-like dopamine receptors."
    Livingstone C.D., Strange P.G., Naylor L.H.
    Biochem. J. 287:277-282(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: 3D-STRUCTURE MODELING.

Entry informationi

Entry nameiDRD2_RAT
AccessioniPrimary (citable) accession number: P61169
Secondary accession number(s): P13953
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: May 10, 2004
Last modified: September 3, 2014
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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