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P61169

- DRD2_RAT

UniProt

P61169 - DRD2_RAT

Protein

D(2) dopamine receptor

Gene

Drd2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 104 (01 Oct 2014)
      Sequence version 1 (10 May 2004)
      Previous versions | rss
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    Functioni

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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei114 – 1141AgonistBy 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

    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

    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

    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...)Sequence Analysis
    Glycosylationi17 – 171N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi23 – 231N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi107 ↔ 182PROSITE-ProRule annotation
    Disulfide bondi400 ↔ 402PROSITE-ProRule annotation

    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.By similarity4 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 3737ExtracellularBy similarityAdd
    BLAST
    Topological domaini61 – 7010CytoplasmicBy similarity
    Topological domaini94 – 10815ExtracellularBy similarityAdd
    BLAST
    Topological domaini131 – 15121CytoplasmicBy similarityAdd
    BLAST
    Topological domaini173 – 18816ExtracellularBy similarityAdd
    BLAST
    Topological domaini214 – 374161CytoplasmicBy similarityAdd
    BLAST
    Topological domaini397 – 41014ExtracellularBy similarityAdd
    BLAST
    Topological domaini433 – 44412CytoplasmicBy similarityAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei38 – 6023Helical; Name=1By similarityAdd
    BLAST
    Transmembranei71 – 9323Helical; Name=2By similarityAdd
    BLAST
    Transmembranei109 – 13022Helical; Name=3By similarityAdd
    BLAST
    Transmembranei152 – 17221Helical; Name=4By similarityAdd
    BLAST
    Transmembranei189 – 21325Helical; Name=5By similarityAdd
    BLAST
    Transmembranei375 – 39622Helical; Name=6By similarityAdd
    BLAST
    Transmembranei411 – 43222Helical; Name=7By similarityAdd
    BLAST

    Family & Domainsi

    Region

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

    Sequence similaritiesi

    Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

    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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti99 – 991E → D in CAA37373. (PubMed:2139615)Curated
    Sequence conflicti173 – 1731G → R in CAA37373. (PubMed:2139615)Curated
    Sequence conflicti180 – 1801N → G in CAA37373. (PubMed:2139615)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei242 – 27029Missing in isoform Short. 1 PublicationVSP_001871Add
    BLAST

    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: October 1, 2014
    This is version 104 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