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Gene Review

CNP  -  2',3'-cyclic nucleotide 3' phosphodiesterase

Homo sapiens

Synonyms: 2',3'-cyclic-nucleotide 3'-phosphodiesterase, CNPase
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Disease relevance of CNP


Psychiatry related information on CNP


High impact information on CNP

  • We report the hormone-binding thermodynamics and crystal structures at 2.9 and 2.0 angstroms, respectively, of the extracellular domain of the unliganded human NP receptor (NPR-C) and its complex with CNP, a 22-amino acid NP [6].
  • In contrast, both isoforms bind the C3 complement, providing a plausible mechanism in MS central nervous system (CNS) for opsonization of myelin membrane CNP, mediated via the C3 receptor, and phagocytosis of CNP-Ig immune complexes, mediated by membrane Ig Fc receptors of macrophages and CNS microglia [7].
  • We report that 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNP), a protein associated with oligodendrocyte/myelin membranes, also present in lymphocytes and retina, is one major target for the humoral response [7].
  • Moreover, CNP is isolated as an immune complex from MS brain [7].
  • CNP is expressed as two isoforms, with CNPII identical to CNPI but with a 20-amino acid extension at the amino terminus of CNPII; however, the antibody response is exclusively restricted to CNPI [7].

Chemical compound and disease context of CNP

  • 3. Although all the known natriuretic peptides, ANP, BNP and CNP are elevated in cor pulmonale, only ANP and BNP appear to have pulmonary vasorelaxant activity in humans [8].
  • In a study of 138 patients with diabetic retinopathy and good fluorescein angiograms, areas of CNP were found in 66.5% using a macular centered photograph [9].
  • Related domains containing the purine NTP-binding sequence pattern have been revealed in two enzymes involved in tRNA processing, yeast tRNA ligase and phage T4 polynucleotide kinase, and in one of the major proteins of mammalian nerve myelin sheath, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) [10].
  • The body weight, liver weight, blood glucose, serum insulin and cerebral CNPase activity were decreased in alcoholic males [11].
  • We performed continuous hyperthermic peritoneal perfusion (CHPP) or continuous normothermic peritoneal perfusion (CNPP) combined with cisplatin (CDDP) 300 mg/kg and mitomycin C (MMC) 30 mg/kg in an attempt to prevent peritoneal recurrence after surgery for gastric cancer [12].

Biological context of CNP


Anatomical context of CNP


Associations of CNP with chemical compounds


Regulatory relationships of CNP

  • When T3 was removed between day 16 and 25, CNP decreased almost to control values and MBP failed to accumulate [22].
  • Treatment of human aortic smooth muscle cells with CNP similarly inhibited both platelet-derived growth factor-induced PAI-1 mRNA expression and PAI-1 protein release by 50% [23].
  • This was coupled with the occurrence of a different subset of CNP cells whose plasma membrane was CNP-immunoreactive and expressed CXCR4 [24].

Other interactions of CNP

  • We found decreased expression of MAG, QKI, TF, and CNP transcripts in white matter [25].
  • With the use of Western blots and dot blot analyses, respectively, GFAP, CNPase, GalC, A2B5 and O4 were found in whole testes and Leydig cell protein extracts of adult men [26].
  • Based on the genotypes observed in these 29 siblings, the human CNP gene was localized to a fragment on 17q bounded by THRA1 (thyroid receptor A1) and NGFR (nerve growth factor receptor), a genetic distance of approximately 6 cM [27].
  • Because a similar progression in the expression of CNP and the HNK-1 epitope occurs during normal oligodendrocyte differentiation, these observations are additional evidence that extensive oligodendrocyte regeneration occurs in some plaques early in the course of the disease [28].
  • Moreover, ANP and CNP, but not BNP mRNA was detectable [29].

Analytical, diagnostic and therapeutic context of CNP


  1. 2',3'-cyclic nucleotide 3'-phosphodiesterase: a novel candidate autoantigen in demyelinating diseases. Rösener, M., Muraro, P.A., Riethmüller, A., Kalbus, M., Sappler, G., Thompson, R.J., Lichtenfels, R., Sommer, N., McFarland, H.F., Martin, R. J. Neuroimmunol. (1997) [Pubmed]
  2. 2',3'-Cyclic nucleotide 3'-phosphodiesterase activity in the cerebrospinal fluid of patients with demyelinating diseases. Suda, H., Hosokawa, T., Ohno, R., Hamaguchi, K., Tsukada, Y. Neurochemical pathology. (1984) [Pubmed]
  3. Molecular markers that identify human astrocytomas and oligodendrogliomas. Popko, B., Pearl, D.K., Walker, D.M., Comas, T.C., Baerwald, K.D., Burger, P.C., Scheithauer, B.W., Yates, A.J. J. Neuropathol. Exp. Neurol. (2002) [Pubmed]
  4. Differential expression of 2':3'-cyclic nucleotide 3'-phosphodiesterase in cultured central, peripheral, and extraneural cells. Sprinkle, T.J., McMorris, F.A., Yoshino, J., DeVries, G.H. Neurochem. Res. (1985) [Pubmed]
  5. Decreased brain levels of 2',3'-cyclic nucleotide-3'-phosphodiesterase in Down syndrome and Alzheimer's disease. Vlkolinský, R., Cairns, N., Fountoulakis, M., Lubec, G. Neurobiol. Aging (2001) [Pubmed]
  6. Allosteric activation of a spring-loaded natriuretic peptide receptor dimer by hormone. He Xl, n.u.l.l., Chow Dc, n.u.l.l., Martick, M.M., Garcia, K.C. Science (2001) [Pubmed]
  7. Dual implication of 2',3'-cyclic nucleotide 3' phosphodiesterase as major autoantigen and C3 complement-binding protein in the pathogenesis of multiple sclerosis. Walsh, M.J., Murray, J.M. J. Clin. Invest. (1998) [Pubmed]
  8. The role of the renin-angiotensin and natriuretic peptide systems in the pulmonary vasculature. Cargill, R.I., Lipworth, B.J. British journal of clinical pharmacology. (1995) [Pubmed]
  9. Retinal ischemia (capillary nonperfusion) in diabetic retinopathy of patients with and without systemic hypertension. Merin, S., Ber, I., Ivry, M. Ophthalmologica (1978) [Pubmed]
  10. Related domains in yeast tRNA ligase, bacteriophage T4 polynucleotide kinase and RNA ligase, and mammalian myelin 2',3'-cyclic nucleotide phosphohydrolase revealed by amino acid sequence comparison. Koonin, E.V., Gorbalenya, A.E. FEBS Lett. (1990) [Pubmed]
  11. Experimental studies on the influence of male alcoholism on fetal development. Tanaka, H., Suzuki, N., Arima, M. Brain Dev. (1982) [Pubmed]
  12. Continuous hyperthermic peritoneal perfusion for the prevention of peritoneal recurrence of gastric cancer: randomized controlled study. Fujimura, T., Yonemura, Y., Muraoka, K., Takamura, H., Hirono, Y., Sahara, H., Ninomiya, I., Matsumoto, H., Tsugawa, K., Nishimura, G. World journal of surgery. (1994) [Pubmed]
  13. Convergent evidence for 2',3'-cyclic nucleotide 3'-phosphodiesterase as a possible susceptibility gene for schizophrenia. Peirce, T.R., Bray, N.J., Williams, N.M., Norton, N., Moskvina, V., Preece, A., Haroutunian, V., Buxbaum, J.D., Owen, M.J., O'Donovan, M.C. Arch. Gen. Psychiatry (2006) [Pubmed]
  14. Gene expression in cells of the central nervous system. Takahashi, Y. Prog. Neurobiol. (1992) [Pubmed]
  15. Structural evidence that brain cyclic nucleotide phosphodiesterase is a member of the 2H phosphodiesterase superfamily. Kozlov, G., Lee, J., Elias, D., Gravel, M., Gutierrez, P., Ekiel, I., Braun, P.E., Gehring, K. J. Biol. Chem. (2003) [Pubmed]
  16. 2',3'-cyclic nucleotide-3'-phosphodiesterase in the central nervous system is fatty-acylated by thioester linkage. Agrawal, H.C., Sprinkle, T.J., Agrawal, D. J. Biol. Chem. (1990) [Pubmed]
  17. Immunohistochemical evidence of inducible nitric oxide synthase and nitrotyrosine in a case of clinically isolated optic neuritis. Tsoi, V.L., Hill, K.E., Carlson, N.G., Warner, J.E., Rose, J.W. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society. (2006) [Pubmed]
  18. Early myelination in the human fetal lumbosacral spinal cord: characterization by light and electron microscopy. Weidenheim, K.M., Kress, Y., Epshteyn, I., Rashbaum, W.K., Lyman, W.D. J. Neuropathol. Exp. Neurol. (1992) [Pubmed]
  19. Disorders in myelination in the twitcher mutant: immunohistochemical and biochemical studies. Mikoshiba, K., Fujishiro, M., Kohsaka, S., Okano, H., Takamatsu, K., Tsukada, Y. Neurochem. Res. (1985) [Pubmed]
  20. 2', 3'-cyclic nucleotide 3'-phosphodiesterase in cerebrospinal fluid. Raes, I., Weissbarth, S., Maker, H.S., Lehrer, G.M. Neurology (1981) [Pubmed]
  21. Ethanol exerts different effects on myelin basic protein and 2',3'-cyclic nucleotide 3'-phosphodiesterase expression in differentiating CG-4 oligodendrocytes. Bichenkov, E., Ellingson, J.S. Brain Res. Dev. Brain Res. (2001) [Pubmed]
  22. Triiodothyronine stimulation of oligodendroglial differentiation and myelination. A developmental study. Almazan, G., Honegger, P., Matthieu, J.M. Dev. Neurosci. (1985) [Pubmed]
  23. Natriuretic factors and nitric oxide suppress plasminogen activator inhibitor-1 expression in vascular smooth muscle cells. Role of cGMP in the regulation of the plasminogen system. Bouchie, J.L., Hansen, H., Feener, E.P. Arterioscler. Thromb. Vasc. Biol. (1998) [Pubmed]
  24. 2', 3'-cyclic nucleotide 3'-phosphodiesterase cells derived from transplanted marrow stromal cells and host tissue contribute to perineurial compartment formation in injured rat spinal cord. Cao, Q., Ding, P., Lu, J., Dheen, S.T., Moochhala, S., Ling, E.A. J. Neurosci. Res. (2007) [Pubmed]
  25. Expression of transcripts for myelination-related genes in the anterior cingulate cortex in schizophrenia. McCullumsmith, R.E., Gupta, D., Beneyto, M., Kreger, E., Haroutunian, V., Davis, K.L., Meador-Woodruff, J.H. Schizophr. Res. (2007) [Pubmed]
  26. Leydig cells of the human testis possess astrocyte and oligodendrocyte marker molecules. Davidoff, M.S., Middendorff, R., Köfüncü, E., Müller, D., Jezek, D., Holstein, A.F. Acta Histochem. (2002) [Pubmed]
  27. Chromosomal mapping of the human CNP gene using a meiotic crossover DNA panel, PCR, and allele-specific probes. Sprinkle, T.J., Kouri, R.E., Fain, P.D., Stoming, T.A., Whitney, J.B. Genomics (1993) [Pubmed]
  28. Multiple sclerosis. Oligodendrocyte proliferation and differentiation in fresh lesions. Prineas, J.W., Kwon, E.E., Goldenberg, P.Z., Ilyas, A.A., Quarles, R.H., Benjamins, J.A., Sprinkle, T.J. Lab. Invest. (1989) [Pubmed]
  29. Differential gene expression of the three natriuretic peptides and natriuretic peptide receptor subtypes in human liver. Vollmar, A.M., Paumgartner, G., Gerbes, A.L. Gut (1997) [Pubmed]
  30. Assignment of the human 2',3'-cyclic nucleotide 3'-phosphohydrolase gene to chromosome 17. Sprinkle, T.J., Lanclos, K.D., Lapp, D.F. Genomics (1992) [Pubmed]
  31. An investigation of 2':3'-cyclic nucleotide 3'-phosphodiesterase (EC, CNP) in peripheral blood elements and CNS myelin. Sheedlo, H.J., Doran, J.E., Sprinkle, T.J. Life Sci. (1984) [Pubmed]
  32. Mechanism of in vitro differentiation of bone marrow stromal cells into neuron-like cells. Chu, Q., Wang, Y., Fu, X., Zhang, S. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban. (2004) [Pubmed]
  33. Crystallization and preliminary X-ray crystallographic studies of human 2',3'-cyclic nucleotide 3'-phosphodiesterase. Sakamoto, Y., Tanaka, N., Ichimiya, T., Kurihara, T., Nakamura, K.T. Acta Crystallogr. D Biol. Crystallogr. (2004) [Pubmed]
  34. Structure and chromosomal localization of the human 2',3'-cyclic nucleotide 3'-phosphodiesterase gene. Douglas, A.J., Fox, M.F., Abbott, C.M., Hinks, L.J., Sharpe, G., Povey, S., Thompson, R.J. Ann. Hum. Genet. (1992) [Pubmed]
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