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2012-01-15T03:31:32Z

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{{PBB|geneid=1267}}
{{enzyme
| Name = 2',3'-Cyclic-nucleotide 3'-phosphodiesterase
| EC_number = 3.1.4.37
| CAS_number = 60098-35-3
| IUBMB_EC_number = 3/1/4/37
| GO_code = 0004113
| image =
| width =
| caption =
}}
'''2',3'-Cyclic-nucleotide 3'-phosphodiesterase''' also known as '''CNPase''' is an [[enzyme]] that in humans is encoded by the ''CNP'' [[gene]].<ref name="pmid1322358">{{cite journal | author = 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=Aug 1992 | pmid = 1322358 | pmc = | 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 = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1267| accessdate = }}</ref>

== Reaction ==

CNPase catalyzes the following reaction:

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

Thus, the two [[substrate (biochemistry)|substrates]] of this enzyme are [[nucleoside 2',3'-cyclic phosphate]] and [[water|H<sub>2</sub>O]], whereas its [[product (chemistry)|product]] is [[nucleoside 2'-phosphate]].

== 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 | author = 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=January 2008 | pmid = 17963267 | doi = 10.1002/glia.20595 | url = | issn = }}</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 | author = Kursula P | title = Structural properties of proteins specific to the myelin sheath | journal = Amino Acids | volume = 34 | issue = 2 | pages = 175–85 |date=February 2008 | pmid = 17177074 | doi = 10.1007/s00726-006-0479-7 | url = | issn = }}</ref>

Structural studies have revealed that four classes of CNPs belong to one protein superfamily. CNP's catalytic core consists of three [[alpha helix|alpha-helices]] and nine [[beta sheet|beta-strands]]. The proposed mechanism of CNPs [[phosphodiesterase]] catalytic activity is similar to the second step of the reaction mechanism for [[ribonuclease A|RNase A]].<ref name="pmid15713463">{{cite journal | author = 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 = J. Mol. Biol. | volume = 346 | issue = 3 | pages = 789–800 |date=February 2005 | pmid = 15713463 | doi = 10.1016/j.jmb.2004.12.024 | url = | issn = }}</ref>

CNP is expressed exclusively by [[oligodendrocyte]]s in the CNS, and the appearance of CNP seems to be one of the earliest events of oligodendrocyte differentiation.<ref name="pmid9326261">{{cite journal | author = 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 = J. Neurochem. | volume = 69 | issue = 4 | pages = 1335–42 |date=October 1997 | pmid = 9326261 | doi = 10.1046/j.1471-4159.1997.69041335.x| url = | issn = }}</ref> CNP is thought to play a critical role in the events leading up to myelination.<ref name="pmid8875429">{{cite journal | author = 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 = Mol. Cell. Neurosci. | volume = 7 | issue = 6 | pages = 453–66 |date=June 1996 | pmid = 8875429 | doi = 10.1006/mcne.1996.0033 | url = | issn = }}</ref>

CNP 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 CNP or [[phosphorylation]] abolish the catalytic activity of microtubule formation. CNP can link tubulin to cellular membranes, and might be involved in the regulation cytoplasmic microtubule distribution.<ref name="pmid11842207">{{cite journal | author = 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 = Proc. Natl. Acad. Sci. U.S.A. | volume = 99 | issue = 4 | pages = 5 |date=February 2002 | pmid = 11842207 | pmc = 122275 | doi = 10.1073/pnas.042678799 | url = | issn = }}</ref>

Interestingly, CNP 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 CNP or a coincidental activity remains unclear <ref name="pmid23084924">{{cite journal | author =Wilson SJ, Schoggins JW, Zang T, Kutluay SB, Jouvenet N, Alim MA, Bitzegeio J, Rice CM, 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=October 2012 | pmid = 23084924 | pmc = 3498451 | doi = 10.1016/j.chom.2012.08.012 | url = | issn = }}</ref>

==References==
{{Reflist}}

==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
* {{cite journal | author = Drummond GI, Iyer NT and Keith J | year = 1962 | title = Hydrolysis of ribonucleoside 2',3'-cyclic phosphates by a diesterase from brain | journal = J. Biol. Chem. | volume = 237 | pages = 3535–3539 }}
* {{cite journal | author = Helfman DM, Kuo JF | year = 1982 | title = A homogeneous cyclic CMP phosphodiesterase hydrolyzes both pyrimidine and purine cyclic 2':3'- and 3':5'-nucleotides | journal = J. Biol. Chem. | volume = 257 | issue = 2 | pages = 1044–7 | pmid = 6274851 }}
* {{cite journal | author = Helfman DM, Shoji M, Kuo JF | year = 1981 | title = Purification to homogeneity and general properties of a novel phosphodiesterase hydrolyzing cyclic CMP and cyclic AMP | journal = J. Biol. Chem. | volume = 256 | issue = 12 | pages = 6327–34 | pmid = 6263914 }}
* {{cite journal | author = Kurihara T, Nishizawa Y, Takahashi Y, Odani S | year = 1981 | title = Chemical, immunological and catalytic properties of 2':3'-cyclic nucleotide 3'-phosphodiesterase purified from brain white matter | journal = Biochem. J. | volume = 195 | issue = 1 | pages = 153–7 | pmid = 6272743 | pmc = 1162865 }}
* {{cite journal | author = Nishizawa Y, Kurihara T, Takahashi Y | year = 1980 | title = Spectrophotometric assay, solubilization and purification of brain 2':3'-cyclic nucleotide 3'-phosphodiesterase | journal = Biochem. J. | volume = 191 | issue = 1 | pages = 71–82 | pmid = 6258586 | pmc = 1162183 }}
*{{cite journal | author=Thompson RJ |title=2',3'-cyclic nucleotide-3'-phosphohydrolase and signal transduction in central nervous system myelin. |journal=Biochem. Soc. Trans. |volume=20 |issue= 3 |pages= 621–6 |year= 1992 |pmid= 1385234 |doi= }}
*{{cite journal | author=Leroy MJ, Dumler I, Lugnier C, ''et al.'' |title=A new peptide (1150Da) selectively activates the calcium-calmodulin sensitive isoform of cyclic nucleotide phosphodiesterase from human myometrium. |journal=Biochem. Biophys. Res. Commun. |volume=184 |issue= 2 |pages= 700–5 |year= 1992 |pmid= 1315529 |doi=10.1016/0006-291X(92)90646-3 }}
*{{cite journal | author=Douglas AJ, Fox MF, Abbott CM, ''et al.'' |title=Structure and chromosomal localization of the human 2',3'-cyclic nucleotide 3'-phosphodiesterase gene. |journal=Ann. Hum. Genet. |volume=56 |issue= Pt 3 |pages= 243–54 |year= 1992 |pmid= 1360194 |doi=10.1111/j.1469-1809.1992.tb01149.x }}
*{{cite journal | author=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=J. Neurosci. Res. |volume=25 |issue= 4 |pages= 556–60 |year= 1990 |pmid= 2161933 |doi= 10.1002/jnr.490250413 }}
*{{cite journal | author=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=J. Biol. Chem. |volume=265 |issue= 20 |pages= 11849–53 |year= 1990 |pmid= 2164018 |doi= }}
*{{cite journal | author=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=Biochem. Biophys. Res. Commun. |volume=152 |issue= 2 |pages= 837–42 |year= 1988 |pmid= 2835044 |doi=10.1016/S0006-291X(88)80114-1 }}
*{{cite journal | author=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=Neurochem. Res. |volume=10 |issue= 7 |pages= 919–31 |year= 1985 |pmid= 2995854 |doi=10.1007/BF00964629 }}
*{{cite journal | author=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 Sci. |volume=34 |issue= 18 |pages= 1731–7 |year= 1984 |pmid= 6328143 |doi=10.1016/0024-3205(84)90572-1 }}
*{{cite journal | author=Monoh K, Kurihara T, Takahashi Y, ''et al.'' |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 |year= 1993 |pmid= 8392017 |doi=10.1016/0378-1119(93)90283-9 }}
*{{cite journal | author=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 |year= 1997 |pmid= 8921398 |doi= 10.1006/geno.1996.0544 }}
*{{cite journal | author=Stricker R, Kalbacher H, Reiser G |title=The epitope recognized by a monoclonal antibody in the myelin-associated protein CNP. |journal=Biochem. Biophys. Res. Commun. |volume=237 |issue= 2 |pages= 266–70 |year= 1997 |pmid= 9268698 |doi=10.1006/bbrc.1997.7125 }}
*{{cite journal | author=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=J. Neurochem. |volume=74 |issue= 2 |pages= 540–6 |year= 2000 |pmid= 10646504 |doi=10.1046/j.1471-4159.2000.740540.x }}
*{{cite journal | author=Zauli G, Milani D, Mirandola P, ''et al.'' |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 J. |volume=15 |issue= 2 |pages= 483–91 |year= 2001 |pmid= 11156964 |doi= 10.1096/fj.00-0354com }}
*{{cite journal | author=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=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 4 |pages= 1807–12 |year= 2002 |pmid= 11842207 | pmc=122275 |doi= 10.1073/pnas.042678799 }}
*{{cite journal | author=Davidoff MS, Middendorff R, Köfüncü E, ''et al.'' |title=Leydig cells of the human testis possess astrocyte and oligodendrocyte marker molecules. |journal=Acta Histochem. |volume=104 |issue= 1 |pages= 39–49 |year= 2002 |pmid= 11993850 |doi=10.1078/0065-1281-00630 }}
*{{cite doi|10.1073/pnas.242603899}}
*{{cite journal | author=Basrur V, Yang F, Kushimoto T, ''et al.'' |title=Proteomic analysis of early melanosomes: identification of novel melanosomal proteins. |journal=J. Proteome Res. |volume=2 |issue= 1 |pages= 69–79 |year= 2003 |pmid= 12643545 |doi=10.1021/pr025562r }}
*{{cite journal | author=Kozlov G, Lee J, Elias D, ''et al.'' |title=Structural evidence that brain cyclic nucleotide phosphodiesterase is a member of the 2H phosphodiesterase superfamily. |journal=J. Biol. Chem. |volume=278 |issue= 46 |pages= 46021–8 |year= 2003 |pmid= 12947117 |doi= 10.1074/jbc.M305176200 }}
}}
{{refend}}
{{PDB Gallery|geneid=1267}}


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[[Category:Human proteins]]

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