View source for 2',3'-Cyclic-nucleotide 3'-phosphodiesterase

{{Short description|Protein-coding gene in the species Homo sapiens}}
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{{infobox enzyme
| align      = left
| Name       = 2′,3′-Cyclic-nucleotide 3'-phosphodiesterase
| EC_number  = 3.1.4.37
| CAS_number = 60098-35-3
| GO_code    = 0004113
| image      =
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{{Infobox_gene}}
'''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]].<ref name="pmid1322358">{{cite journal | vauthors = Sprinkle TJ, Lanclos KD, Lapp DF | title = Assignment of the human 2′,3′-cyclic nucleotide 3′-phosphohydrolase gene to chromosome 17 | journal = Genomics | volume = 13 | issue = 3 | pages = 877–80 | date = Jul 1992 | pmid = 1322358 | doi = 10.1016/0888-7543(92)90174-Q }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: CNP 2′,3′-cyclic nucleotide 3′-phosphodiesterase| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1267}}</ref>

== Reaction ==

CNPase catalyzes the following reaction:

:nucleoside 2′,3′-cyclic phosphate + H<sub>2</sub>O <math>\rightleftharpoons</math> nucleoside 2′-phosphate

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== Function ==

CNPase is a [[myelin]]-associated enzyme that makes up 4% of total [[central nervous system|CNS]] myelin protein, and is thought to undergo significant age-associated changes.<ref name="pmid17963267">{{cite journal | vauthors = Hinman JD, Chen CD, Oh SY, Hollander W, Abraham CR | title = Age-dependent accumulation of ubiquitinated 2',3'-cyclic nucleotide 3'-phosphodiesterase in myelin lipid rafts | journal = Glia | volume = 56 | issue = 1 | pages = 118–33 | date = Jan 2008 | pmid = 17963267 | doi = 10.1002/glia.20595 | s2cid = 8729201 }}</ref> It is named for its ability to catalyze the [[phosphodiester bond|phosphodiester]] [[hydrolysis]] of 2',3'-cyclic nucleotides to 2'-nucleotides, though a cohesive understanding of its specific physiologic functions are still ambiguous.<ref name="pmid17177074">{{cite journal | vauthors = Kursula P | title = Structural properties of proteins specific to the myelin sheath | journal = Amino Acids | volume = 34 | issue = 2 | pages = 175–85 | date = Feb 2008 | pmid = 17177074 | doi = 10.1007/s00726-006-0479-7 | s2cid = 20270722 }}</ref>

Structural studies have revealed that four classes of CNPases belong to one protein superfamily. CNPase's catalytic core consists of three [[alpha helix|alpha-helices]] and nine [[beta sheet|beta-strands]]. The proposed mechanism of CNPases [[phosphodiesterase]] catalytic activity is similar to the second step of the reaction mechanism for [[ribonuclease A|RNase A]].<ref name="pmid15713463">{{cite journal | vauthors = Sakamoto Y, Tanaka N, Ichimiya T, Kurihara T, Nakamura KT | title = Crystal structure of the catalytic fragment of human brain 2',3'-cyclic-nucleotide 3'-phosphodiesterase | journal = Journal of Molecular Biology | volume = 346 | issue = 3 | pages = 789–800 | date = Feb 2005 | pmid = 15713463 | doi = 10.1016/j.jmb.2004.12.024 }}</ref>

CNPase is expressed exclusively by [[oligodendrocyte]]s in the CNS, and the appearance of CNPase seems to be one of the earliest events of oligodendrocyte differentiation.<ref name="pmid9326261">{{cite journal | vauthors = Kasama-Yoshida H, Tohyama Y, Kurihara T, Sakuma M, Kojima H, Tamai Y | title = A comparative study of 2',3'-cyclic-nucleotide 3'-phosphodiesterase in vertebrates: cDNA cloning and amino acid sequences for chicken and bullfrog enzymes | journal = Journal of Neurochemistry | volume = 69 | issue = 4 | pages = 1335–42 | date = Oct 1997 | pmid = 9326261 | doi = 10.1046/j.1471-4159.1997.69041335.x | doi-access = free }}</ref> CNPase is thought to play a critical role in the events leading up to myelination.<ref name="pmid8875429">{{cite journal | vauthors = Gravel M, Peterson J, Yong VW, Kottis V, Trapp B, Braun PE | title = Overexpression of 2',3'-cyclic nucleotide 3'-phosphodiesterase in transgenic mice alters oligodendrocyte development and produces aberrant myelination | journal = Molecular and Cellular Neurosciences | volume = 7 | issue = 6 | pages = 453–66 | date = Jun 1996 | pmid = 8875429 | doi = 10.1006/mcne.1996.0033 | s2cid = 35687881 }}</ref>

CNPase also associates with [[microtubule]]s 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.<ref name="pmid11842207">{{cite journal | vauthors = Bifulco M, Laezza C, Stingo S, Wolff J | title = 2',3'-Cyclic nucleotide 3'-phosphodiesterase: a membrane-bound, microtubule-associated protein and membrane anchor for tubulin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 4 | pages = 1807–12 | date = Feb 2002 | pmid = 11842207 | pmc = 122275 | doi = 10.1073/pnas.042678799 | bibcode = 2002PNAS...99.1807B | doi-access = free }}</ref>

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.<ref name="pmid23084924">{{cite journal | vauthors = Wilson SJ, Schoggins JW, Zang T, Kutluay SB, Jouvenet N, Alim MA, Bitzegeio J, Rice CM, [[Paul Bieniasz|Bieniasz PD]] | title = Inhibition of HIV-1 particle assembly by 2′,3′-cyclic-nucleotide 3′-phosphodiesterase | journal = Cell Host & Microbe | volume = 12 | issue = 4 | pages = 585–97 | date = Oct 2012 | pmid = 23084924 | pmc = 3498451 | doi = 10.1016/j.chom.2012.08.012 }}</ref>
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== References ==
{{Reflist|33em}}

==External links==
* {{UCSC gene info|CNP}}

== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Drummond GI, Iyer NT, Keith J | year = 1962 | title = Hydrolysis of ribonucleoside 2',3'-cyclic phosphates by a diesterase from brain | journal = J. Biol. Chem.  | volume = 237 | issue = 11 | pages = 3535–3539 | doi = 10.1016/S0021-9258(19)70852-7 | doi-access = free }}
* {{cite journal | vauthors = Helfman DM, Kuo JF | title = A homogeneous cyclic CMP phosphodiesterase hydrolyzes both pyrimidine and purine cyclic 2':3'- and 3':5'-nucleotides | journal = The Journal of Biological Chemistry | volume = 257 | issue = 2 | pages = 1044–7  | date = Jan 1982 | doi = 10.1016/S0021-9258(19)68305-5 | pmid = 6274851 | doi-access = free }}
* {{cite journal | vauthors = Helfman DM, Shoji M, Kuo JF | title = Purification to homogeneity and general properties of a novel phosphodiesterase hydrolyzing cyclic CMP and cyclic AMP | journal = The Journal of Biological Chemistry | volume = 256 | issue = 12 | pages = 6327–34  | date = Jun 1981 | doi = 10.1016/S0021-9258(19)69166-0 | pmid = 6263914 | doi-access = free }}
* {{cite journal | vauthors = Kurihara T, Nishizawa Y, Takahashi Y, Odani S | title = Chemical, immunological and catalytic properties of 2':3'-cyclic nucleotide 3'-phosphodiesterase purified from brain white matter | journal = The Biochemical Journal | volume = 195 | issue = 1 | pages = 153–7  | date = Apr 1981 | pmid = 6272743 | pmc = 1162865 | doi = 10.1042/bj1950153 }}
* {{cite journal | vauthors = Nishizawa Y, Kurihara T, Takahashi Y | title = Spectrophotometric assay, solubilization and purification of brain 2':3'-cyclic nucleotide 3'-phosphodiesterase | journal = The Biochemical Journal | volume = 191 | issue = 1 | pages = 71–82  | date = Oct 1980 | pmid = 6258586 | pmc = 1162183 | doi = 10.1042/bj1910071 }}
* {{cite journal | vauthors = Thompson RJ | title = 2',3'-cyclic nucleotide-3'-phosphohydrolase and signal transduction in central nervous system myelin | journal = Biochemical Society Transactions | volume = 20 | issue = 3 | pages = 621–6  | date = Aug 1992 | pmid = 1385234 | doi =  10.1042/bst0200621 }}
* {{cite journal | vauthors = Leroy MJ, Dumler I, Lugnier C, Shushakova ND, Ferré F | title = A new peptide (1150Da) selectively activates the calcium-calmodulin sensitive isoform of cyclic nucleotide phosphodiesterase from human myometrium | journal = Biochemical and Biophysical Research Communications | volume = 184 | issue = 2 | pages = 700–5  | date = Apr 1992 | pmid = 1315529 | doi = 10.1016/0006-291X(92)90646-3 | display-authors = 1 }}
* {{cite journal | vauthors = Douglas AJ, Fox MF, Abbott CM, Hinks LJ, Sharpe G, Povey S, Thompson RJ | title = Structure and chromosomal localization of the human 2',3'-cyclic nucleotide 3'-phosphodiesterase gene | journal = Annals of Human Genetics | volume = 56 | issue = Pt 3 | pages = 243–54  | date = Jul 1992 | pmid = 1360194 | doi = 10.1111/j.1469-1809.1992.tb01149.x | s2cid = 34627658 | display-authors = 1 }}
* {{cite journal | vauthors = Staugaitis SM, Bernier L, Smith PR, Colman DR | title = Expression of the oligodendrocyte marker 2'3'-cyclic nucleotide 3'-phosphodiesterase in non-glial cells | journal = Journal of Neuroscience Research | volume = 25 | issue = 4 | pages = 556–60  | date = Apr 1990 | pmid = 2161933 | doi = 10.1002/jnr.490250413 | s2cid = 29416130 }}
* {{cite journal | vauthors = Agrawal HC, Sprinkle TJ, Agrawal D | title = 2',3'-cyclic nucleotide-3'-phosphodiesterase in the central nervous system is fatty-acylated by thioester linkage | journal = The Journal of Biological Chemistry | volume = 265 | issue = 20 | pages = 11849–53  | date = Jul 1990 | doi = 10.1016/S0021-9258(19)38476-5 | pmid = 2164018 | doi-access = free }}
* {{cite journal | vauthors = Kurihara T, Takahashi Y, Nishiyama A, Kumanishi T | title = cDNA cloning and amino acid sequence of human brain 2',3'-cyclic-nucleotide 3'-phosphodiesterase | journal = Biochemical and Biophysical Research Communications | volume = 152 | issue = 2 | pages = 837–42  | date = Apr 1988 | pmid = 2835044 | doi = 10.1016/S0006-291X(88)80114-1 }}
* {{cite journal | vauthors = Sprinkle TJ, McMorris FA, Yoshino J, DeVries GH | title = Differential expression of 2':3'-cyclic nucleotide 3'-phosphodiesterase in cultured central, peripheral, and extraneural cells | journal = Neurochemical Research | volume = 10 | issue = 7 | pages = 919–31  | date = Jul 1985 | pmid = 2995854 | doi = 10.1007/BF00964629 | s2cid = 34362955 }}
* {{cite journal | vauthors = Sheedlo HJ, Doran JE, Sprinkle TJ | title = An investigation of 2':3'-cyclic nucleotide 3'-phosphodiesterase (EC 3.1.4.37, CNP) in peripheral blood elements and CNS myelin | journal = Life Sciences | volume = 34 | issue = 18 | pages = 1731–7  | date = Apr 1984 | pmid = 6328143 | doi = 10.1016/0024-3205(84)90572-1 }}
* {{cite journal | vauthors = Monoh K, Kurihara T, Takahashi Y, Ichikawa T, Kumanishi T, Hayashi S, Minoshima S, Shimizu N | title = Structure, expression and chromosomal localization of the gene encoding human 2',3'-cyclic-nucleotide 3'-phosphodiesterase | journal = Gene | volume = 129 | issue = 2 | pages = 297–301  | date = Jul 1993 | pmid = 8392017 | doi = 10.1016/0378-1119(93)90283-9 | display-authors = 1 }}
* {{cite journal | vauthors = Löbbert RW, Winterpacht A, Seipel B, Zabel BU | title = 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 | journal = Genomics | volume = 37 | issue = 2 | pages = 211–8 | date = Oct 1996 | pmid = 8921398 | doi = 10.1006/geno.1996.0544 }}
* {{cite journal | vauthors = Stricker R, Kalbacher H, Reiser G | title = The epitope recognized by a monoclonal antibody in the myelin-associated protein CNP | journal = Biochemical and Biophysical Research Communications | volume = 237 | issue = 2 | pages = 266–70  | date = Aug 1997 | pmid = 9268698 | doi = 10.1006/bbrc.1997.7125 }}
* {{cite journal | vauthors = O'Neill RC, Braun PE | title = Selective synthesis of 2',3'-cyclic nucleotide 3'-phosphodiesterase isoform 2 and identification of specifically phosphorylated serine residues | journal = Journal of Neurochemistry | volume = 74 | issue = 2 | pages = 540–6  | date = Feb 2000 | pmid = 10646504 | doi = 10.1046/j.1471-4159.2000.740540.x | s2cid = 25697047 | doi-access = free }}
* {{cite journal | vauthors = Zauli G, Milani D, Mirandola P, Mazzoni M, Secchiero P, Miscia S, Capitani S | title = HIV-1 Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/AKT/cyclic nucleoside phosphodiesterase pathway | journal = FASEB Journal | volume = 15 | issue = 2 | pages = 483–91  | date = Feb 2001 | pmid = 11156964 | doi = 10.1096/fj.00-0354com | doi-access = free | s2cid = 26315564 | display-authors = 1 }}
* {{cite journal | vauthors = Bifulco M, Laezza C, Stingo S, Wolff J | title = 2',3'-Cyclic nucleotide 3'-phosphodiesterase: a membrane-bound, microtubule-associated protein and membrane anchor for tubulin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 4 | pages = 1807–12  | date = Feb 2002 | pmid = 11842207 | pmc = 122275 | doi = 10.1073/pnas.042678799 | bibcode = 2002PNAS...99.1807B | doi-access = free }}
* {{cite journal | vauthors = Davidoff MS, Middendorff R, Köfüncü E, Müller D, Jezek D, Holstein AF | title = Leydig cells of the human testis possess astrocyte and oligodendrocyte marker molecules | journal = Acta Histochemica | volume = 104 | issue = 1 | pages = 39–49 | year = 2002 | pmid = 11993850 | doi = 10.1078/0065-1281-00630 | display-authors = 1 }}
* {{cite journal | vauthors = Basrur V, Yang F, Kushimoto T, Higashimoto Y, Yasumoto K, Valencia J, Muller J, Vieira WD, Watabe H, Shabanowitz J, Hearing VJ, Hunt DF, Appella E | title = Proteomic analysis of early melanosomes: identification of novel melanosomal proteins | journal = Journal of Proteome Research | volume = 2 | issue = 1 | pages = 69–79 | year = 2003 | pmid = 12643545 | doi = 10.1021/pr025562r | display-authors = 1 }}
* {{cite journal | vauthors = Kozlov G, Lee J, Elias D, Gravel M, Gutierrez P, Ekiel I, Braun PE, Gehring K | title = Structural evidence that brain cyclic nucleotide phosphodiesterase is a member of the 2H phosphodiesterase superfamily | journal = The Journal of Biological Chemistry | volume = 278 | issue = 46 | pages = 46021–8  | date = Nov 2003 | pmid = 12947117 | doi = 10.1074/jbc.M305176200 | display-authors = 1 | doi-access = free }}
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{{PDB Gallery|geneid=1267}}
{{Esterases}}

[[Category:Human proteins]]