RGD Reference Report - Dopamine D4 receptor repeat: analysis of different native and mutant forms of the human and rat genes. - Rat Genome Database

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Dopamine D4 receptor repeat: analysis of different native and mutant forms of the human and rat genes.

Authors: Asghari, V  Schoots, O  Van Kats, S  Ohara, K  Jovanovic, V  Guan, HC  Bunzow, JR  Petronis, A  Van Tol, HH 
Citation: Asghari V, etal., Mol Pharmacol. 1994 Aug;46(2):364-73.
RGD ID: 7248459
Pubmed: PMID:8078498   (View Abstract at PubMed)

Recent molecular characterization of the human D4 gene has revealed the existence of various polymorphic forms of this receptor. These variations are found in the putative third cytoplasmic loop region and encode a variable number of repeats of 16 amino acids in length. In the present study we have compared the pharmacological binding profiles of seven different polymorphic variants of the human D4 receptor, the rat D4 receptor, and two different human D4 receptor mutants that were deleted in the repeat sequence. For this purpose we cloned the rat D4 receptor gene and compared its gene structure and its pharmacological binding profile with those of the D4.4 and D4.7 genes. The rat and human D4 genes display a high degree of sequence similarity, especially in the coding regions. An Alu repeat sequence was identified in the first intron of the human D4 gene but is not present in the rat D4 gene. Furthermore, using the polymerase chain reaction we cloned 3-, 5-, 6-, and 9-fold repeat sequences. These cloned repeat sequences were used for the reconstruction of full length cDNAs encoding D4.3, D4.5, D4.6, and D4.9, respectively. These novel forms of the human D4 receptor, as well as the previously cloned D4.2, D4.4, and D4.7 forms, were transiently expressed in COS-7 cells. All of the different forms of the human and rat D4 receptors and repeat deletion mutants displayed similar binding profiles for all ligands tested, although small differences were observed. The affinity for dopamine could be decreased by guanosine-5'-(beta, gamma-imido)triphosphate with the different forms of the D4 receptor, including the two receptor mutants that were deleted in the repeat sequence. These data suggest that the polymorphic repeat sequence has little influence on D4 binding profiles and might not be essential for G protein interaction.

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
(+)-butaclamol affects bindingISODrd4 (Rattus norvegicus)7248459; 7248459Butaclamol binds to Drd4 proteinRGD 
(+)-butaclamol affects bindingEXP 7248459Butaclamol binds to Drd4 proteinRGD 
clozapine affects bindingISODrd4 (Rattus norvegicus)7248459; 7248459Clozapine binds to Drd4 proteinRGD 
clozapine affects bindingEXP 7248459Clozapine binds to Drd4 proteinRGD 
dopamine affects bindingISODrd4 (Rattus norvegicus)7248459; 7248459Dopamine binds to Drd4 proteinRGD 
dopamine affects bindingEXP 7248459Dopamine binds to Drd4 proteinRGD 
haloperidol affects bindingISODrd4 (Rattus norvegicus)7248459; 7248459Haloperidol binds to Drd4 proteinRGD 
haloperidol affects bindingEXP 7248459Haloperidol binds to Drd4 proteinRGD 
sodium chloride multiple interactionsISODrd4 (Rattus norvegicus)7248459; 7248459NaCl inhibits the reaction [Quinpirole binds to Drd4 protein]RGD 
sodium chloride multiple interactionsEXP 7248459NaCl inhibits the reaction [Quinpirole binds to Drd4 protein]RGD 
spiperone affects bindingISODrd4 (Rattus norvegicus)7248459; 7248459Spiperone binds to Drd4 proteinRGD 
spiperone affects bindingEXP 7248459Spiperone binds to Drd4 proteinRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dopamine binding  IPIdopamine7248459 RGD 
heterocyclic compound binding  IPIspiperone more ...7248459 RGD 
heterocyclic compound binding  IDA 7248459emonapride and PHNORGD 

Objects Annotated

Genes (Rattus norvegicus)
Drd4  (dopamine receptor D4)

Genes (Mus musculus)
Drd4  (dopamine receptor D4)

Genes (Homo sapiens)
DRD4  (dopamine receptor D4)


Additional Information