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Gene Review

NPR3  -  natriuretic peptide receptor 3

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High impact information on NPR3

  • The mature form of ANP-C has a disulfide-linked homodimeric structure and contains 5 conserved cysteine residues per subunit, all in the extracellular domain [1].
  • Alignment of the cDNA sequences with that of the ANP-C gene indicated that the two forms of ANP-C receptor arise from a single gene by alternative splicing using one donor and two closely located acceptor sites [2].
  • A novel form of type C atrial natriuretic peptide receptor (ANP-C) was identified, characterized, and shown to be a product of alternative RNA splicing [2].
  • Sequencing of several clones of ANP-C cDNA isolated from a bovine lung cDNA library revealed the presence of a new clone encoding a 536-amino acid ANP-C [2].
  • The nucleotide sequence of this novel clone is very similar to that of the previously cloned ANP-C which consists of 537 amino acids [2].

Biological context of NPR3


Anatomical context of NPR3


Associations of NPR3 with chemical compounds

  • This analog, which retains many of the spatial relationships of the native molecule, binds to both ANP-A and ANP-C receptor subtypes, and triggers the production of cyclic-GMP by ANP-A [8].
  • ANP[13-27][1-8], a truncated analog in which much of this binding domain has been removed, surprisingly maintains a high affinity for ANP-C; however, this peptide has lost the ability to activate the ANP-A-linked guanylate cyclase [8].
  • ANP-C binding of ANP[13-27][1- 12] is roughly equipotent to that of ANP itself, although the ring cleavage falls within the putative ANP-C binding domain [8].
  • 32P labeled cells, NPR-C purification and phosphoamino acid analysis clearly demonstrate that NPR-C exists as a phosphoprotein in RASM cells and that phosphorylation occurs exclusively on serine residues [3].

Other interactions of NPR3

  • Quantitative analysis of the ribonuclease protection assay showed that the numbers of type A receptor (ANPRA) mRNA were 6.9 x 10(7) in the glomeruli and 10.4 x 10(7) molecules/micrograms of total RNA in the inner medulla, and that of type C receptor (ANPRC) mRNA was 21.7 x 10(7) molecules/micrograms of total RNA in the glomeruli [6].

Analytical, diagnostic and therapeutic context of NPR3


  1. Mutational analysis of disulfide bridges in the type C atrial natriuretic peptide receptor. Itakura, M., Iwashina, M., Mizuno, T., Ito, T., Hagiwara, H., Hirose, S. J. Biol. Chem. (1994) [Pubmed]
  2. A variant form of the type C atrial natriuretic peptide receptor generated by alternative RNA splicing. Mizuno, T., Iwashina, M., Itakura, M., Hagiwara, H., Hirose, S. J. Biol. Chem. (1993) [Pubmed]
  3. Characterization of the phosphorylation state of natriuretic peptide receptor-C. Pedro, L., Fenrick, R., Marquis, M., McNicoll, N., De Léan, A. Mol. Cell. Biochem. (1998) [Pubmed]
  4. His145-Trp146 residues and the disulfide-linked loops in atrial natriuretic peptide receptor are critical for the ligand-binding activity. Iwashina, M., Mizuno, T., Hirose, S., Ito, T., Hagiwara, H. J. Biochem. (1994) [Pubmed]
  5. Regulation of natriuretic peptide receptors by thyrotropin in FRTL-5 rat thyroid cells: evidence for nonguanylate cyclase atrial natriuretic factor-binding sites in cells lacking the natriuretic peptide receptor C. Sellitti, D.F., Doi, S.Q. Endocrinology (1999) [Pubmed]
  6. Expression of mRNA for natriuretic peptide receptor subtypes in bovine kidney. Yamamoto, T., Feng, L., Mizuno, T., Hirose, S., Kawasaki, K., Yaoita, E., Kihara, I., Wilson, C.B. Am. J. Physiol. (1994) [Pubmed]
  7. G protein-dependent activation of smooth muscle eNOS via natriuretic peptide clearance receptor. Murthy, K.S., Teng, B., Jin, J., Makhlouf, G.M. Am. J. Physiol. (1998) [Pubmed]
  8. A ring-reversed analog of atrial natriuretic peptide retains receptor binding, guanylate cyclase stimulation. von Geldern, T.W., Budzik, G.P., Dillon, T.P. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
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