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

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.^[5][6]

2′,3′-Cyclic-nucleotide 3'-phosphodiesterase
Identifiers
EC no.	3.1.4.37
CAS no.	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 / QuickGO
Search PMC articles PubMed articles NCBI proteins

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)[1] Band 17q21.2 Start 41,966,763 bp[1] End 41,977,740 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 D|11 63.47 cM Start 100,465,730 bp[2] End 100,482,555 bp[2]
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 [3] [4]
Wikidata
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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.^[7] 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.^[8]

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.^[9]

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.^[10] CNPase is thought to play a critical role in the events leading up to myelination.^[11]

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.^[12]

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.^[13]