Atrial natriuretic peptide receptor 1

Function

Receptor for the atrial natriuretic peptide NPPA/ANP and the brain natriuretic peptide NPPB/BNP which are potent vasoactive hormones playing a key role in cardiovascular homeostasis. Plays an essential role in the regulation of endothelial cell senescence and vascular aging. Upon activation by ANP or BNP, stimulates the production of cyclic guanosine monophosphate (cGMP) that promotes vascular tone and volume homeostasis by activation of protein kinase cGMP-dependent 1/PRKG1 and subsequently PRKAA1, thereby controlling blood pressure and maintaining cardiovascular homeostasis.

Classification

Family (Pfam)

PF01094 ANF_receptor, PF00211 Guanylate_cyc, PF07714 PK_Tyr_Ser-Thr

InterPro

A/G_cyclase, A/G_cyclase_CS, ANF_lig-bd_rcpt, ANPR/GUC, Cyclic_nucleotide_synthase, Kinase-like_dom_sf, Nucleotide_cyclase, Peripla_BP_I, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom

Functional cluster

Secreted Growth Factors & Cytokines

Experimental structures · PDB · 9

• 8TG9 EM 3.08A
• 8TGA EM 3.65A
• 9BCL EM 2.90A
• 9BCN EM 2.90A
• 9BCO EM 4.40A
• 9BCP EM 4.10A
• 9BCQ EM 3.10A
• 9BCS EM 4.40A
• 9BCV EM 3.20A

A predicted model is available from AlphaFold.

Gene Ontology · 27

• GO:0005789 endoplasmic reticulum membrane
• GO:0031965 nuclear membrane
• GO:0005886 plasma membrane
• GO:0043235 receptor complex
• GO:0005524 ATP binding
• GO:0008528 G protein-coupled peptide receptor activity
• GO:0005525 GTP binding
• GO:0004383 guanylate cyclase activity
• GO:0042562 hormone binding
• GO:0016941 natriuretic peptide receptor activity
• GO:0017046 peptide hormone binding
• GO:0001653 peptide receptor activity
• GO:0004672 protein kinase activity
• GO:0097746 blood vessel diameter maintenance
• GO:0007589 body fluid secretion
• GO:0007166 cell surface receptor signaling pathway
• GO:0006182 cGMP biosynthetic process
• GO:0042417 dopamine metabolic process
• GO:0035556 intracellular signal transduction
• GO:0016525 negative regulation of angiogenesis
• GO:0030308 negative regulation of cell growth
• GO:0048662 negative regulation of smooth muscle cell proliferation
• GO:0035815 positive regulation of renal sodium excretion
• GO:0035810 positive regulation of urine volume
• GO:0007168 receptor guanylyl cyclase signaling pathway
• GO:0008217 regulation of blood pressure
• GO:0043114 regulation of vascular permeability

Drugs targeting this protein · 2

• CARPERITIDE agonist
• PL-3994 agonist

Related proteins · sequence + function similarity

• Atrial natriuretic peptide receptor 1 0.99
• Atrial natriuretic peptide receptor 1 0.99
• Atrial natriuretic peptide receptor 2 0.95
• Atrial natriuretic peptide receptor 2 0.95
• Atrial natriuretic peptide receptor 2 0.94
• Atrial natriuretic peptide receptor 2 0.94
• Guanylate cyclase 2D 0.82
• Retinal guanylyl cyclase 1 0.82
• Retinal guanylyl cyclase 1 0.81
• Guanylate cyclase D 0.81
• Retinal guanylyl cyclase 1 0.81
• Retinal guanylyl cyclase 1 0.80

Co-cited proteins · studied together in the literature

• Atrial natriuretic peptide receptor 2 3 shared papers
• Atrial natriuretic peptide receptor 2 1 shared papers
• Atrial natriuretic peptide receptor 1 1 shared papers
• Atrial natriuretic peptide receptor 3 1 shared papers
• Natriuretic peptides A 2 shared papers
• C-type natriuretic peptide 1 shared papers
• Natriuretic peptides B 1 shared papers

Literature · 12 cited papers

• Architecture and activation of single-pass transmembrane receptor guanylyl cyclase. Nat. Struct. Mol. Biol. · 2024
• Chronological attenuation of NPRA/PKG/AMPK signaling promotes vascular aging and elevates blood pressure. Aging Cell · 2022
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Mass spectrometric identification of phosphorylation sites in guanylyl cyclase A and B. Biochemistry · 2010
• Patterns of somatic mutation in human cancer genomes. Nature · 2007
• The DNA sequence and biological annotation of human chromosome 1. Nature · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Organization of the human natriuretic peptide receptor A gene. Biochem. Biophys. Res. Commun. · 1998
• Expression of mRNA for atrial natriuretic peptide receptor guanylate cyclase (ANPRA) in human retina. Cell. Mol. Neurobiol. · 1994
• Human atrial natriuretic peptide receptor defines a new paradigm for second messenger signal transduction. EMBO J. · 1989
• Selective activation of the B natriuretic peptide receptor by C-type natriuretic peptide (CNP). Science · 1991
• Extracellular domain-IgG fusion proteins for three human natriuretic peptide receptors. Hormone pharmacology and application to solid phase screening of synthetic peptide antisera. J. Biol. Chem. · 1991