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FLASH GENE

Symbol

NPPA

contributors: mct/npt - updated : 12-01-2018

HGNC name	natriuretic peptide precursor A
HGNC id	7939

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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 Cardiovascular heart atrium     highly Homo sapiens Digestive salivary gland parotid     highly Homo sapiens Adult   salivary gland parotid     highly Homo sapiens Fetal Nervous brain       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum cardiac   highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Muscular myocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo

Text	in the trabecular layer of the left ventricle and weakly expressed in the atrium and the trabecular layer of the right ventricle
	in pre-implantation embryos and in self-renewing sembryonic stem cells

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a signal sequence
	conserved 17-AAs disulfide-linked ring structure that is required for biological activity (Dickey 2009)
	a region of homology to the porcine vasoactive peptide cardiodilatin and the atrial natriuretic factor (ANF) in the C terminal region

isoforms

Precursor

HOMOLOGY

Homologene

FAMILY

natriuretic peptide family

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,cytosolic,granule
	intracellular,nucleus

basic FUNCTION	directly influencing blood pressure, body fluid homeostasis and kidney function
	regulates sodium and water balance, blood pressure and myocardial mass through direct effects on the kidney, vasculature and heart and is involved in the pathophysiology of hypertension and heart failure
	NPPB, NPPA, NPPC activate guanylyl cyclase suggesting a potential role in maintaining lens epithelial cell homeostasis (PMID;
	regulate lipid and carbohydrate metabolism providing a possible link between cardiovascular function and metabolism by mediating the switch from carbohydrate to lipid mobilization and oxidation
	regulates lipid metabolism and oxygen utilization in differentiated adipocytes by activating the alpha2 subunit of AMPK
	enhances mitochondrial function as evidenced by increased oxygen consumption and induction of key mitochondrial genes
	regulates lipid catabolism and enhances energy dissipation through AMPK activation in adipocytes
	new function of corin and NPPA in promoting trophoblast invasion and spiral artery remodelling
	profoundly inhibits evoked release of glutamate from the axonal terminals of medial habenula (MHb) to the interpeduncular nucleus (IPN) neurons
	blocks neurotransmission by depleting presynaptic cAMP concentrations
	might play a role in the differentiation of the parotid gland similarly as in brain and during fetal growth NPPA may play a role in the regulating the secretion of primitive salivary fluid, even if acini are still not developed
	concerted action of NPPA and DRD1 to regulate sodium homeostasis in nephrotic syndrome
	protective mechanism of NPPA against pathologic vascular hyperpermeability, suggesting a novel pharmacological intervention for the prevention of increased vascular leak via PAK1-dependent modulation of ARHGEF2 activity
	early and specific marker for functional myocardium of the embryonic heart
	importance of the endogenous NPPA/NPPB-NPR1 system not only in the neovascularization of ischemic tissues but also in embryonic vascular development and organ morphogenesis
	importance of KLF10 and NPPA/NPR1 in exerting influences on chronic pulmonary disease pathogenesis
	enhances endothelial barrier function by reducing RHOA activity and reorganizing the actin cytoskeleton

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule

protein	OSTN binds to NPR3 competitively with NPPA and may affect NPPA concentrations in a local or systemic manner
	selective activation of the PRKAA2 by NPPA is essential for NPPA mediated lipolysis in adipocytes and has several important potential implications which are relevant to the role of NPPA in exercise, heart failure and obesity and insulin resistance
	NKX2-5 and its responsive cis-regulatory DNA elements are essential for NPPA expression selectively in the developing heart
	PDE2A plays an essential role in the NPPA effect on synaptic transmission
	cooperative mechanism where ANXA6 potentiates NPPA-dependent counterhypertrophic responses in cardiomyocytes by facilitating regulated traffic of pro-NPPA
	in the developing mammalian ventricles NPPA plays a local paracrine role in regulating the balance between cardiac progenitor cell (CPC) proliferation and differentiation via NPR1/cGMP-mediated signaling pathways
	via its receptor, NPR1, NPPA maintains cardiovascular homeostasis by exerting diuretic, natriuretic, and hypotensive effects mediated, in part, by endothelial cells
	CCM2 and PAK4 are important downstream mediators of NPPA/NPR1 signaling involved in cell spreading, an important initial step in the enhancement of endothelial barrier function
	NSD3 decreases NPPA expression and, thereby, attenuates ISO-induced cardiomyocyte hypertrophy

cell & other

REGULATION

induced by

CAMTA1, which induces the expression of the anti-proliferative cardiac hormone natriuretic peptide A (NPPA)

ASSOCIATED DISORDERS

corresponding disease(s)

ATFB6 , ATRST2

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in congestive heart failure

Susceptibility

to nephropathy and microvascular damage in type 1 diabetes to blood pressure variation development of ischemic stroke to cardioembolic stroke

Variant & Polymorphism other	polymorphism 2238C affect the course of nephropathy in inadequately controlled type 1 diabetic patients
	common genetic variants at the NPPA-NPPB locus found to be associated with circulating natriuretic peptide concentrations contribute to interindividual variation in blood pressure and hypertension (Newton-Cheh 2009)
	association between frequent nonsynonymous variant of NPPA and cardioembolic stroke
	NPPA genetic polymorphism and serum NPPA levels may contribute to the development of ischemic stroke

Candidate gene
Marker	NPPA genetic polymorphism and serum NPPA levels could be potential biomarkers for early detection of ischemic stroke
	marker of heart failure in children with left ventricular volume overload
Therapy target

ANIMAL & CELL MODELS

pregnant corin- or Nppa-deficient mice developed high blood pressure and proteinuria, characteristics of pre-eclampsia