Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

NPR1

contributors: mct/npt - updated : 26-03-2018

HGNC name	natriuretic peptide receptor A/guanylate cyclase A (atrionatriuretic peptide receptor A)
HGNC id	7943

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	1q21.3      Physical location : 153.651.163 - 153.666.467
Synonym name	atrial natriuretic peptide
	guanylate cyclase A
Synonym symbol(s)	ANPRA, GUC2A, NPRA, ANPa, GUCY2A, ANP, GC-A
EC.number	4.6.1.2

DNA

TYPE	functioning gene
STRUCTURE	15.30 kb     22 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000906 22 - 4201 NP_000897 - 1061 - 2008 18656450 GC-A splice variant - - - - - ubiquiously expressed 2008 18656450 deletion of 17 AAs (Lys314–Gln330) in the membrane-distal part of the extracellular domain has unique structural properties that impede ligand binding and ligand-induced guanylyl cyclase activity can form heterodimers with wild type NPR1 thereby interfering with ANP signaling

EXPRESSION

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 Cardiovascular vessels         Endocrine adrenal gland         Nervous nerve       highly Reproductive female system breast mammary gland   highly Respiratory respiratory tract trachea     highly Urinary kidney         Visual eye retina macula     Rattus norvegicus

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly Epithelial secretory glandular endocrine

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell Visual ganglion cell Rattus norvegicus

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo

Text	in pre-implantation embryos and in self-renewing sembryonic stem cells

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a 450-AAs extracellular ligand-binding domain
	a 21-AA hydrophobic membrane-spanning region
	a 566-amino acid intracellular domain with intrinsic guanylate cyclase activity
	a single transmembrane domain (TM), and an intracellular domain (ICD) exhibiting guanylyl cyclase activity
	a protein kinase-like domain
	seven sites of glycosylation
	in addition to the GC domain, the kinase homology domain was also required for NPPA/NPR1 signaling
	cytoplasmic domains of both NPR1 and NPR2 display a guanylate cyclase activity that catalyzes the formation of cyclic GMP 0)

conjugated

GlycoP

HOMOLOGY

interspecies	ortholog to rattus Npr1
	ortholog to murine Npr1

Homologene

FAMILY

adenylyl cyclase class-4/guanylyl cyclase family

CATEGORY

enzyme , receptor membrane G

SUBCELLULAR LOCALIZATION	plasma membrane
text	single-pass type I membrane protein

basic FUNCTION	acting as a natriuretic peptide, receptor A
	acting as a membrane guanylate cyclase GC-A
	mediating vasorelaxant and natriuretic functions and decreasing aldosterone synthesis
	involved in blood pressure regulation
	involved in negative regulation of angiogenesis
	playing a role in negative regulation of cell growth
	involved in regulation of vasodilatation
	NPR1 and PRKG2 are selectively induced in granulosa cells of preovulatory follicles by LH- and PR-dependent mechanisms, thereby providing a pathway for cGMP function during ovulation
	critical roles in the control of fluid volume, blood pressure, cardiac remodeling, and other physiological functions and pathological states
	role for NPR1 in the maintenance of self-renewal and pluripotency of ES cells
	in cardiomyocytes from failing human hearts is refractory to NPPA stimulation
	its renoprotective properties may result from the local inhibition of the renin-angiotensin-aldosterone system and oxidative stress in podocytes
	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

CELLULAR PROCESS	cell life, proliferation/growth

PHYSIOLOGICAL PROCESS

cardiovascular , excretion

text

diuresis

PATHWAY

metabolism

nucleic

signaling

cGMP biosynthesis

a component

INTERACTION

DNA

RNA

small molecule	nucleotide,
	ATP

protein	Npr1 gene transcription is critically controlled by histone acetyltransferase EP300 and ETS1
	specific receptor for atrial and brain natriuretic peptides (NPPA, NPPB)
	PDE2A serves likely as the downstream transducer of cGMP signals produced by NPR1 activation
	vasonatrin peptide stimulates both of the natriuretic peptide receptors, NPR1 and NPR2
	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
	KLF10 acts as a transcriptional repressor of NPR1
	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
	DPP4, AGTR2, SLC4A1, KREMEN1, ASGR1, NPR1, TMEM30A, CLEC4G, and LDLRAD3, along with ACE2 facilitate SARS-CoV-2. virus entry and transmission

cell & other

REGULATION

Other

responding to ANP (NPPA) and to a lesser degree to BNP

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in esophageal squamous cell carcinomas

Susceptibility

to nephritis and progressive renal failure (see RFH1) to hypertension to myocardial infarction development of left ventricular hypertrophy (LVH) in patients with hypertension

Variant & Polymorphism SNP , other	mutated in myocardial infarction
	A2843G polymorphism in the promoter might be a genetic risk factor for the development of LVH in hypertension

Candidate gene
Marker	potential prognostic marker in prostate cancer
Therapy target
	System Type Disorder Pubmed cancer reproductive prostate target for prostate cancer therapy

ANIMAL & CELL MODELS

	after 4 weeks of administering aldosterone and a high-salt diet, Gc-a knockout mice, but not wild-type mice, exhibited accelerated hypertension with massive proteinuria
	disruption of Npr1 gene activates proinflammatory cytokines leading to fibrosis, hypertrophic growth, and remodeling of the kidneys of mutant mice