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CNP
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1WOJ
Identifiers
Aliases	CNP, CNP1, 2',3'-cyclic nucleotide 3' phosphodiesterase, CNPase, HLD20
External IDs	OMIM: 123830; MGI: 88437; HomoloGene: 7672; GeneCards: CNP; OMA:CNP - orthologs
EC number	3.1.4.37
Gene location (Human) Chr. Chromosome 17 (human) Band 17q21.2 Start 41,966,763 bp End 41,977,740 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11 D|11 63.47 cM Start 100,465,730 bp End 100,482,555 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in inferior olivary nucleus inferior ganglion of vagus nerve C1 segment olfactory bulb external globus pallidus corpus callosum pars reticulata subthalamic nucleus optic nerve internal globus pallidus Top expressed in optic nerve deep cerebellar nuclei sciatic nerve globus pallidus ventral tegmental area lateral geniculate nucleus pontine nuclei utricle medial geniculate nucleus substantia nigra More reference expression data BioGPS More reference expression data
Gene ontology Molecular function RNA binding hydrolase activity cyclic nucleotide binding 2',3'-cyclic-nucleotide 3'-phosphodiesterase activity Cellular component cytoplasm cell projection pseudopodium membrane melanosome myelin sheath plasma membrane myelin sheath adaxonal region myelin sheath abaxonal region microvillus mitochondrial outer membrane perinuclear region of cytoplasm mitochondrial inner membrane microtubule extracellular exosome extracellular space nucleus nucleoplasm cytosol Biological process substantia nigra development axonogenesis adult locomotory behavior ageing oligodendrocyte differentiation response to lipopolysaccharide regulation of mitochondrial membrane permeability forebrain development response to toxic substance microtubule cytoskeleton organization cyclic nucleotide catabolic process chemical synaptic transmission Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1267 12799 Ensembl ENSG00000173786 ENSMUSG00000006782 UniProt P09543 P16330 RefSeq (mRNA) NM_033133 NM_001330216 NM_001146318 NM_009923 RefSeq (protein) NP_001317145 NP_149124 NP_001139790 NP_034053 Location (UCSC) Chr 17: 41.97 – 41.98 Mb Chr 11: 100.47 – 100.48 Mb PubMed search
Wikidata
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2′,3′-Cyclic-nucleotide 3'-phosphodiesterase (EC 3.1.4.37, CNPase, systematic name nucleoside-2′,3′-cyclic-phosphate 2′-nucleotidohydrolase) is an enzyme that in humans is encoded by the CNP gene.

Reaction

CNPase catalyzes the following reaction:

nucleoside 2′,3′-cyclic phosphate + H₂O ${\displaystyle \rightleftharpoons }$ nucleoside 2′-phosphate

Function

CNPase is a myelin-associated enzyme that makes up 4% of total CNS myelin protein, and is thought to undergo significant age-associated changes. It is named for its ability to catalyze the phosphodiester hydrolysis of 2',3'-cyclic nucleotides to 2'-nucleotides, though a cohesive understanding of its specific physiologic functions are still ambiguous.

Structural studies have revealed that four classes of CNPases belong to one protein superfamily. CNPase's catalytic core consists of three alpha-helices and nine beta-strands. The proposed mechanism of CNPases phosphodiesterase catalytic activity is similar to the second step of the reaction mechanism for RNase A.

CNPase is expressed exclusively by oligodendrocytes in the CNS, and the appearance of CNPase seems to be one of the earliest events of oligodendrocyte differentiation. CNPase is thought to play a critical role in the events leading up to myelination.

CNPase also associates with microtubules in brain tissue and FRTL-5 thyroid cells, and is reported to have microtubule-associated protein-like activity (MAP; see MAP2), being able to catalyze microtubule formation at low molar ratios. Deletion of the C-terminus of CNPase or phosphorylation abolish the catalytic activity of microtubule formation. CNPase can link tubulin to cellular membranes, and might be involved in the regulation cytoplasmic microtubule distribution.

CNPase has also been demonstrated to inhibit the replication of HIV-1 and other primate lentiviruses by binding the retroviral Gag protein and inhibiting the genesis of nascent viral particles. Whether this is a biological function of CNPase or a coincidental activity remains unclear.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000173786 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000006782 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Sprinkle TJ, Lanclos KD, Lapp DF (Jul 1992). "Assignment of the human 2′,3′-cyclic nucleotide 3′-phosphohydrolase gene to chromosome 17". Genomics. 13 (3): 877–80. doi:10.1016/0888-7543(92)90174-Q. PMID 1322358.
6. "Entrez Gene: CNP 2′,3′-cyclic nucleotide 3′-phosphodiesterase".
7. Hinman JD, Chen CD, Oh SY, Hollander W, Abraham CR (Jan 2008). "Age-dependent accumulation of ubiquitinated 2',3'-cyclic nucleotide 3'-phosphodiesterase in myelin lipid rafts". Glia. 56 (1): 118–33. doi:10.1002/glia.20595. PMID 17963267. S2CID 8729201.
8. Kursula P (Feb 2008). "Structural properties of proteins specific to the myelin sheath". Amino Acids. 34 (2): 175–85. doi:10.1007/s00726-006-0479-7. PMID 17177074. S2CID 20270722.
9. Sakamoto Y, Tanaka N, Ichimiya T, Kurihara T, Nakamura KT (Feb 2005). "Crystal structure of the catalytic fragment of human brain 2',3'-cyclic-nucleotide 3'-phosphodiesterase". Journal of Molecular Biology. 346 (3): 789–800. doi:10.1016/j.jmb.2004.12.024. PMID 15713463.
10. Kasama-Yoshida H, Tohyama Y, Kurihara T, Sakuma M, Kojima H, Tamai Y (Oct 1997). "A comparative study of 2',3'-cyclic-nucleotide 3'-phosphodiesterase in vertebrates: cDNA cloning and amino acid sequences for chicken and bullfrog enzymes". Journal of Neurochemistry. 69 (4): 1335–42. doi:10.1046/j.1471-4159.1997.69041335.x. PMID 9326261.
11. Gravel M, Peterson J, Yong VW, Kottis V, Trapp B, Braun PE (Jun 1996). "Overexpression of 2',3'-cyclic nucleotide 3'-phosphodiesterase in transgenic mice alters oligodendrocyte development and produces aberrant myelination". Molecular and Cellular Neurosciences. 7 (6): 453–66. doi:10.1006/mcne.1996.0033. PMID 8875429. S2CID 35687881.
12. Bifulco M, Laezza C, Stingo S, Wolff J (Feb 2002). "2',3'-Cyclic nucleotide 3'-phosphodiesterase: a membrane-bound, microtubule-associated protein and membrane anchor for tubulin". Proceedings of the National Academy of Sciences of the United States of America. 99 (4): 1807–12. Bibcode:2002PNAS...99.1807B. doi:10.1073/pnas.042678799. PMC 122275. PMID 11842207.
13. Wilson SJ, Schoggins JW, Zang T, Kutluay SB, Jouvenet N, Alim MA, Bitzegeio J, Rice CM, Bieniasz PD (Oct 2012). "Inhibition of HIV-1 particle assembly by 2′,3′-cyclic-nucleotide 3′-phosphodiesterase". Cell Host & Microbe. 12 (4): 585–97. doi:10.1016/j.chom.2012.08.012. PMC 3498451. PMID 23084924.

External links

• Human CNP genome location and CNP gene details page in the UCSC Genome Browser.

Further reading

• Drummond GI, Iyer NT, Keith J (1962). "Hydrolysis of ribonucleoside 2',3'-cyclic phosphates by a diesterase from brain". J. Biol. Chem. 237 (11): 3535–3539. doi:10.1016/S0021-9258(19)70852-7.
• Helfman DM, Kuo JF (Jan 1982). "A homogeneous cyclic CMP phosphodiesterase hydrolyzes both pyrimidine and purine cyclic 2':3'- and 3':5'-nucleotides". The Journal of Biological Chemistry. 257 (2): 1044–7. doi:10.1016/S0021-9258(19)68305-5. PMID 6274851.
• Helfman DM, Shoji M, Kuo JF (Jun 1981). "Purification to homogeneity and general properties of a novel phosphodiesterase hydrolyzing cyclic CMP and cyclic AMP". The Journal of Biological Chemistry. 256 (12): 6327–34. doi:10.1016/S0021-9258(19)69166-0. PMID 6263914.
• Kurihara T, Nishizawa Y, Takahashi Y, Odani S (Apr 1981). "Chemical, immunological and catalytic properties of 2':3'-cyclic nucleotide 3'-phosphodiesterase purified from brain white matter". The Biochemical Journal. 195 (1): 153–7. doi:10.1042/bj1950153. PMC 1162865. PMID 6272743.
• Nishizawa Y, Kurihara T, Takahashi Y (Oct 1980). "Spectrophotometric assay, solubilization and purification of brain 2':3'-cyclic nucleotide 3'-phosphodiesterase". The Biochemical Journal. 191 (1): 71–82. doi:10.1042/bj1910071. PMC 1162183. PMID 6258586.
• Thompson RJ (Aug 1992). "2',3'-cyclic nucleotide-3'-phosphohydrolase and signal transduction in central nervous system myelin". Biochemical Society Transactions. 20 (3): 621–6. doi:10.1042/bst0200621. PMID 1385234.
• Leroy MJ, et al. (Apr 1992). "A new peptide (1150Da) selectively activates the calcium-calmodulin sensitive isoform of cyclic nucleotide phosphodiesterase from human myometrium". Biochemical and Biophysical Research Communications. 184 (2): 700–5. doi:10.1016/0006-291X(92)90646-3. PMID 1315529.
• Douglas AJ, et al. (Jul 1992). "Structure and chromosomal localization of the human 2',3'-cyclic nucleotide 3'-phosphodiesterase gene". Annals of Human Genetics. 56 (Pt 3): 243–54. doi:10.1111/j.1469-1809.1992.tb01149.x. PMID 1360194. S2CID 34627658.
• Staugaitis SM, Bernier L, Smith PR, Colman DR (Apr 1990). "Expression of the oligodendrocyte marker 2'3'-cyclic nucleotide 3'-phosphodiesterase in non-glial cells". Journal of Neuroscience Research. 25 (4): 556–60. doi:10.1002/jnr.490250413. PMID 2161933. S2CID 29416130.
• Agrawal HC, Sprinkle TJ, Agrawal D (Jul 1990). "2',3'-cyclic nucleotide-3'-phosphodiesterase in the central nervous system is fatty-acylated by thioester linkage". The Journal of Biological Chemistry. 265 (20): 11849–53. doi:10.1016/S0021-9258(19)38476-5. PMID 2164018.
• Kurihara T, Takahashi Y, Nishiyama A, Kumanishi T (Apr 1988). "cDNA cloning and amino acid sequence of human brain 2',3'-cyclic-nucleotide 3'-phosphodiesterase". Biochemical and Biophysical Research Communications. 152 (2): 837–42. doi:10.1016/S0006-291X(88)80114-1. PMID 2835044.
• Sprinkle TJ, McMorris FA, Yoshino J, DeVries GH (Jul 1985). "Differential expression of 2':3'-cyclic nucleotide 3'-phosphodiesterase in cultured central, peripheral, and extraneural cells". Neurochemical Research. 10 (7): 919–31. doi:10.1007/BF00964629. PMID 2995854. S2CID 34362955.
• Sheedlo HJ, Doran JE, Sprinkle TJ (Apr 1984). "An investigation of 2':3'-cyclic nucleotide 3'-phosphodiesterase (EC 3.1.4.37, CNP) in peripheral blood elements and CNS myelin". Life Sciences. 34 (18): 1731–7. doi:10.1016/0024-3205(84)90572-1. PMID 6328143.
• Monoh K, et al. (Jul 1993). "Structure, expression and chromosomal localization of the gene encoding human 2',3'-cyclic-nucleotide 3'-phosphodiesterase". Gene. 129 (2): 297–301. doi:10.1016/0378-1119(93)90283-9. PMID 8392017.
• Löbbert RW, Winterpacht A, Seipel B, Zabel BU (Oct 1996). "Molecular cloning and chromosomal assignment of the human homologue of the rat cGMP-inhibited phosphodiesterase 1 (PDE3A)--a gene involved in fat metabolism located at 11p 15.1". Genomics. 37 (2): 211–8. doi:10.1006/geno.1996.0544. PMID 8921398.
• Stricker R, Kalbacher H, Reiser G (Aug 1997). "The epitope recognized by a monoclonal antibody in the myelin-associated protein CNP". Biochemical and Biophysical Research Communications. 237 (2): 266–70. doi:10.1006/bbrc.1997.7125. PMID 9268698.
• O'Neill RC, Braun PE (Feb 2000). "Selective synthesis of 2',3'-cyclic nucleotide 3'-phosphodiesterase isoform 2 and identification of specifically phosphorylated serine residues". Journal of Neurochemistry. 74 (2): 540–6. doi:10.1046/j.1471-4159.2000.740540.x. PMID 10646504. S2CID 25697047.
• Zauli G, et al. (Feb 2001). "HIV-1 Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/AKT/cyclic nucleoside phosphodiesterase pathway". FASEB Journal. 15 (2): 483–91. doi:10.1096/fj.00-0354com. PMID 11156964. S2CID 26315564.
• Bifulco M, Laezza C, Stingo S, Wolff J (Feb 2002). "2',3'-Cyclic nucleotide 3'-phosphodiesterase: a membrane-bound, microtubule-associated protein and membrane anchor for tubulin". Proceedings of the National Academy of Sciences of the United States of America. 99 (4): 1807–12. Bibcode:2002PNAS...99.1807B. doi:10.1073/pnas.042678799. PMC 122275. PMID 11842207.
• Davidoff MS, et al. (2002). "Leydig cells of the human testis possess astrocyte and oligodendrocyte marker molecules". Acta Histochemica. 104 (1): 39–49. doi:10.1078/0065-1281-00630. PMID 11993850.
• Basrur V, et al. (2003). "Proteomic analysis of early melanosomes: identification of novel melanosomal proteins". Journal of Proteome Research. 2 (1): 69–79. doi:10.1021/pr025562r. PMID 12643545.
• Kozlov G, et al. (Nov 2003). "Structural evidence that brain cyclic nucleotide phosphodiesterase is a member of the 2H phosphodiesterase superfamily". The Journal of Biological Chemistry. 278 (46): 46021–8. doi:10.1074/jbc.M305176200. PMID 12947117.

• Genes on human chromosome 17
• Human proteins