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FLASH GENE

Symbol

DRD2

contributors: mct/pgu - updated : 31-08-2016

HGNC name	dopamine receptor D2
HGNC id	3023

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	65.68 kb     8 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

Y

status

confirmed

Map	cen - D11S84 - TYR - D11S35 - MMP8 - MMP10 - MMP8 - MMP3 - MMP12 - MMP7 - D11S385 - MMP13 - D11S611 - D11S384 - D11S424 - D11S444 - NCAM1 - DRD2 - D11S386 - D11S351 - D11S144 - D11S29 - HMBS - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000795 8 - 2713 NM_000795 50.5 443 - 2015 26308580 D2L exhibited calcium-dependent desensitization similar to that exhibited by endogenous autoreceptors expression of D2S as the exclusive autoreceptor was insufficient for cocaine-induced plasticity, implying a functional role for the co-expression of D2S and D2L autoreceptors NM_016574 7 - 2626 NP_057658 47.2 414 - 2015 26308580 D2S expression of D2S as the exclusive autoreceptor was insufficient for cocaine-induced plasticity, implying a functional role for the co-expression of D2S and D2L autoreceptors

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine neuroendocrine pituitary       Nervous brain midbrain       Homo sapiens   brain basal nuclei striatum     Homo sapiens   nerve spinal nerve sciatic

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol Nervous dopaminergic neuron Homo sapiens Nervous neuron Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	eye, retina, eye anterior segment, lens choroid, RPE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

a large intracytoplasmic loop between segments 5 and 6

HOMOLOGY

Homologene

FAMILY

G-protein coupled receptor 1 family

CATEGORY

receptor membrane G

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic,vesicle

basic FUNCTION	adenylate cyclase inhibiting, involved in the regulation of appetite and growth hormone
	having distinct functional roles with dopamine in the cortex versus the striatum
	TAAR1 and DRD2 have functional and physical interactions that could be critical for the modulation of the dopaminergic system by TAAR1
	dopamine DRD2 signaling suppresses human osteoclastogenesis
	new function of DRD2 in dendritic spine morphogenesis
	key receptor that mediates dopamine-associated brain functions such as mood, reward, and emotion
	play likely an important role in the activity-dependent functional development of the retina
	differential roles of DRD1 and DRD2 receptor-containing neurons of the nucleus accumbens shell in behavioral sensitization
	exhibits pleiotropic responses to the biogenic amine dopamine (DA) to mediate complex central nervous system functions through activation of G proteins and beta-arrestins
	functional expression of DRD2 is regulated by tetraspanin 7-mediated postendocytic trafficking

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

hormonal , neurotransmission

a component

INTERACTION

DNA

RNA

small molecule

protein	calnexin interactions critically regulate DRD2
	NOVA1 and HNRNPM are DRD2 pre-mRNA-binding proteins with antagonistic role in the alternative splicing of DRD2 pre-mRNA
	functional interaction between TAAR1 and DRD2
	expression of ZNF804A results in a statistically significant decrease in transcript levels of PDE4B and DRD2
	association of ANKK1/DRD2 implicates the role of nicotine-related pathways and dopamine signaling in language processing, particularly in comprehension and phonological memory
	CDK5-mediated phosphorylation of S321 inhibits DRD2 function, providing a novel regulatory mechanism for dopamine signaling
	DRD2, via paraoxonase 2 and SESN2, keeps normal renal redox balance, which contributes to the maintenance of normal blood pressure
	interactions between DRD2 and GNB5 are not mediated by endogenously expressed RGS7 proteins
	is a prominent target for drug treatments in disorders where dopamine function is aberrant, such as schizophrenia
	NCS1 interacts with both the G-protein-coupled receptor (GPCR) DRD2, regulating its internalization and surface expression, and the cognate kinases GRK1 and ADBRK1
	ZDHHC3 and ZDHHC8, also interacted with the DRD2 and each of the palmitoyl acyltransferase (PAT) was capable of affecting the palmitoylation status of the DRD2
	TSPAN7 negatively affects DRD2-mediated signaling

cell & other

REGULATION

Other	regulated by DNA methylation
	ADRBK1 or ADRBK2 promotes its phosphorylation and regulates its post-endocytic trafficking

ASSOCIATED DISORDERS

corresponding disease(s)

MD

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       loss of function dysfunction during adolescence impairs neuronal circuits and working memory, and indicate that adolescent interventions to prevent aberrant DRD2 activity protect against cognitive impairment constitutional       loss of function is a critical mechanism mediating cocaine-induced glutamate plasticity in ventral tegmental area (VTA) neurons

Susceptibility

to opium addiction in Iranian population to schizophrenia to suicide to speech disfluency to nicotine dependence (ND) and alcohol dependence (AD)

Variant & Polymorphism SNP , other	may be association of the S311C variant with schizophrenia
	141C ins/del asociated with schizophrenia and alcoholism
	allele A1-A1 increases the risk of opium addiction in Iranian population
	polymorphisms that may be involved in the biological susceptibility to suicide
	C allele at rs6277 is associated with increased susceptibility to speech disfluency
	association of DRD2 and its adjacent gene ankyrin repeat and kinase domain containing 1 (ANKK1) with nicotine dependence (ND) and alcohol dependence (AD)

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed psychiatry     potential impact of future therapeutic strategies that enhance DRD2 signaling in the nucleus accumbens (NAc) tumor     DRD2 and SSTR3 seem to be the most promising targets for pharmacological treatment of pituitary adenomas

ANIMAL & CELL MODELS