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FLASH GENE

Symbol

PDE2A

contributors: mct - updated : 10-01-2018

HGNC name	phosphodiesterase 2A, cGMP-stimulated
HGNC id	8777

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	COCH Childhood-Onset Chorea
Location	11q13.4      Physical location : 72.287.185 - 72.385.494
Synonym name	cAMP specific nucleotide phosphodiesterase, class II
	cGMP-stimulated phosphodiesterase 4
Synonym symbol(s)	PDE2, PDE2A1, PED2A4, CGS-PDE1, cGSPDE
EC.number	3.1.4.17

DNA

TYPE	functioning gene
STRUCTURE	104.45 kb     31 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002599 31 - 4329 NP_002590 105.7 941 - 2009 19632989 PDE2A3, soluble NM_001143839 30 - 4147 NP_001137311 - 934 - 2011 21724846 PDE2A2 located in the mitochondrial matrix and the unique N terminus of PDE2A isoform 2 specifically leads to mitochondrial localization of this isoform specifically targeted to the mitochondrial matrix, where it forms a local signaling system with soluble adenylyl cyclase regulating the respiratory chain novel regulator of mitochondrial cAMP signals that modulate oxidative phosphorylation NM_001146209 32 - 4197 - 932 - 2009 19632989 PDE2A4 membrane-bound enzyme myristoylation underlies membrane targeting of PDE2A4 NM_001243784 - - 4208 NP_001230713 - 920 - 2009 19632989 PDE2A1

EXPRESSION

Rna function	mRNA was high in the claustrum and putamen
Type	widely

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 adrenal gland cortex zona glomerula     Homo sapiens Nervous brain limbic system hippocampus   highly Homo sapiens   brain diencephalon amygdala   highly Homo sapiens   brain basal nuclei striatum   highly Homo sapiens   brain forebrain cerebral cortex     Rattus norvegicus

cells

System Cell Pubmed Species Stage Rna symbol Nervous epithelial cell Homo sapiens Nervous neuron Homo sapiens Nervous pyramidal cell Rattus norvegicus

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two GAF domains
	a C terminal phosphodiesterase domain

HOMOLOGY

intraspecies

paralog to PDE10A

Homologene

FAMILY

cyclic nucleotide phosphodiesterase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,mitochondria,inner
	intracellular,cytoplasm,organelle,mitochondria,outer
	intracellular,cytoplasm,organelle,mitochondria,matrix
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,microtubule
	intracellular,nucleus
text	localizes to synaptosomal membranes
	with GUCA1A are coexpressed in the same population of the olfactory sensory neurons
	presence of GUCY2D, GUCA1A, and PDE2A predominant in the cilia, yet to a lesser degree, they are also present in other regions of the olfactory neurons

basic FUNCTION	having 3',5'-cyclic nucleotide phosphodiesterase activity
	hydrolyzing both cyclic AMP (cAMP) and cyclic GMP (cGMP)
	potentially TNF-alpha-mediated up-regulation of PDE2A may destabilize endothelial barrier function in sepsis
	regulates the basal cGMP concentration in thalamic neurons
	promotes activation of NADPH oxidase-dependent ROS production and subsequent endothelial proliferation and angiogenesis
	plays a fundamental role in signal transduction
	plays a major role in regulating dopamine-stimulated cAMP production in striatal neurons
	preferential distribution of PDE2A into axons and terminals of the principal neurons suggests roles in regulation of axonal excitability or transmitter release
	PDE2A serves likely as the downstream transducer of cGMP signals produced by NPR1 activation
	PDE2A performs likely the important function of regulating neurotransmitter release by negatively linking cGMP signals to the cAMP pathway
	appears to play an important role in growth and invasion of the human malignant melanoma PMP cell line
	exerts its action on cognitive processes via the control of intracellular second messengers, cGMP and, to a lesser extent, cAMP

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule

protein	PDE2A plays an essential role in the NPPA effect on synaptic transmission
	interaction with over-expressed AIP does not seem to affect PDE2A function, but the reported effect on PDE4A is, in contrast, reduced enzymatic activity

cell & other

REGULATION

Other

inhibition of PDE2A, by enhancing the hormone-dependent cAMP response locally, affects mitochondria dynamics and protects from apoptotic cell death

ASSOCIATED DISORDERS

corresponding disease(s)

COCH

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   may provide a brake against the inhibitory action of NPPB on sympathetic transmission constitutional     --over   in failing hearts and desensitizes against ADRB1 stimulation

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed psychiatry     PDE2A inhibitors could be used as pharmacological drugs for treatment of anxiety and nicotine addiction via their actions on medial habenula (MHb) axonal terminals miscelleaneous vascular   targeting PDE2A may provide a new therapeutic approach in diseases associated with endothelial dysfunction, oxidative stress, vascular proliferation, and angiogenesis respiratory     inhibition of PDE2A is of potential therapeutic interest in sepsis and acute respiratory distress syndrome (ARDS)

ANIMAL & CELL MODELS