2',3'-Cyclic-nucleotide 3'-phosphodiesterase

CNP
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1WOJ
Identifiers
Aliases	CNP, CNP1, 2',3'-cyclic nucleotide 3' phosphodiesterase
External IDs	OMIM: 123830 MGI: 88437 HomoloGene: 7672 GeneCards: CNP
EC number	3.1.4.37
Gene ontology Molecular function • 2',3'-cyclic-nucleotide 3'-phosphodiesterase activity • RNA binding • hydrolase activity • cyclic nucleotide binding Cellular component • cytoplasm • cell projection • pseudopodium • membrane • melanosome • myelin sheath • plasma membrane • myelin sheath adaxonal region • nucleoplasm • extracellular space • myelin sheath abaxonal region • microvillus • mitochondrial outer membrane • perinuclear region of cytoplasm • mitochondrial inner membrane • microtubule • extracellular exosome • nucleus Biological process • substantia nigra development • axonogenesis • adult locomotory behavior • aging • 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
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1267	12799
Ensembl	ENSG00000173786	ENSMUSG00000006782
UniProt	P09543	P16330
RefSeq (mRNA)	NM_033133	NM_001146318 NM_009923
RefSeq (protein)	NP_149124.3	NP_001139790.1 NP_034053.2
Location (UCSC)	Chr 17: 41.97 – 41.98 Mb	Chr 11: 100.57 – 100.59 Mb
PubMed search	[1]	[2]
Wikidata

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2',3'-Cyclic-nucleotide 3'-phosphodiesterase also known as CNPase is an enzyme that in humans is encoded by the CNP gene.^[3][4]

Reaction

2',3'-Cyclic-nucleotide 3'-phosphodiesterase
Identifiers
EC number	3.1.4.37
CAS number	60098-35-3
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles NCBI proteins

CNPase catalyzes the following reaction:

nucleoside 2',3'-cyclic phosphate + H₂O $\rightleftharpoons$ nucleoside 2'-phosphate

Thus, the two substrates of this enzyme are nucleoside 2',3'-cyclic phosphate and H₂O, whereas its product is 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.^[5] 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.^[6]

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.^[7]

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.^[8] CNPase is thought to play a critical role in the events leading up to myelination.^[9]

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.^[10]

Interestingly, 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.^[11]

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. 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.
4. "Entrez Gene: CNP 2',3'-cyclic nucleotide 3' phosphodiesterase".
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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: 3535–3539.
• 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. 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. 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. 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. 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.
• 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.
• 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. 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.
• 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.
• 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.
• 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.