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Information on EC 3.1.4.37 - 2',3'-cyclic-nucleotide 3'-phosphodiesterase and Organism(s) Rattus norvegicus and UniProt Accession P13233
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3.1.4.37 2',3'-cyclic-nucleotide 3'-phosphodiesteraseIUBMB Comments
The brain enzyme acts on 2',3'-cyclic AMP more rapidly than on the UMP or CMP derivatives. An enzyme from liver acts on 2',3'-cyclic CMP more rapidly than on the purine derivatives; it also hydrolyses the corresponding 3',5'-cyclic phosphates, but more slowly. This latter enzyme has been called cyclic-CMP phosphodiesterase.
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Word Map
- 3.1.4.37
- myelin
- oligodendrocyte
- glial
- mbp
- matter
- astrocyte
- nerve
- demyelination
- cord
-
fibrillary
- sclerosis
-
myelin-associated
- sheath
-
proteolipid
- cerebral
- oligodendroglial
-
corpus
-
schwann
- callosum
- sulfatide
- microglia
- nestin
- galactocerebroside
-
sciatic
-
3\'-cyclic
-
myelin-specific
-
myelin-related
-
hypomyelination
- 5'-nucleotidase
-
myelinogenesis
- neurofilament
- galactolipids
- medicine
- diagnostics
-
luxol
-
ensheathing
- cuprizone
-
quaking
- cerebroside
-
paranodal
-
jimpy
-
cuprizone-induced
-
shiverer
-
myelin-like
-
myelin-forming
-
oligodendrocyte-specific
- analysis
-
oligodendrogenesis
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
cnpase, 2',3'-cyclic nucleotide 3'-phosphodiesterase, 2',3'-cyclic nucleotide 3'-phosphohydrolase, 2',3'-cyclic-nucleotide 3'-phosphodiesterase, 2',3'-cyclic nucleotide-3'-phosphodiesterase, 2',3'-cyclic nucleotide-3'-phosphohydrolase, 2':3'-cyclic nucleotide 3'-phosphodiesterase, 2',3'-cyclic nucleotide phosphodiesterase, 2',3'-cyclic-nucleotide 3'-phosphodiesterase type i, 2':3'-cnmp-3'-ase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
2',3'-cyclic AMP phosphodiesterase
-
-
-
-
2',3'-cyclic nucleoside monophosphate phosphodiesterase
-
-
-
-
2',3'-cyclic nucleotide 3'-phosphodiesterase
-
-
2',3'-cyclic nucleotide 3'-phosphohydrolase
-
-
-
-
2',3'-cyclic nucleotide phosphohydrolase
-
-
-
-
2':3'-cyclic nucleotide 3'-phosphodiesterase
-
-
-
-
CNP
CNP1
CNPase
cyclic 2',3'-nucleotide 3'-phosphodiesterase
-
-
-
-
cyclic 2',3'-nucleotide phosphodiesterase
-
-
-
-
cyclic-CMP phosphodiesterase
-
-
-
-
nucleoside-2':3'-cyclic-phosphate 2'-nucleotidohydrolase
-
-
-
-
phosphodiesterase, cyclic 2',3'-nucleotide 3'-
-
-
-
-
CNP
-
-
-
-
CNPase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
nucleoside-2',3'-cyclic-phosphate 2'-nucleotidohydrolase
The brain enzyme acts on 2',3'-cyclic AMP more rapidly than on the UMP or CMP derivatives. An enzyme from liver acts on 2',3'-cyclic CMP more rapidly than on the purine derivatives; it also hydrolyses the corresponding 3',5'-cyclic phosphates, but more slowly. This latter enzyme has been called cyclic-CMP phosphodiesterase.
CAS REGISTRY NUMBER
COMMENTARY
60098-35-3
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
-
-
-
?
1,N6-etheno-2-azaadenosine-2',3'-cyclic monophosphate + H2O
etheno-2-azaadenosine-2'-monophosphate
-
-
-
-
?
1,N6-ethenoadenosine-2',3'-cyclic monophosphate + H2O
ethenoadenosine-2'-monophosphate
-
-
-
-
?
2',3'-cAMP + H2O
3'-AMP + ?
-
the exclusive formation of 3'-AMP is due to the P-O2' bond having lower activation energy and is not the result of steric exclusion at enzyme active site, kinetic evidence that hydrolysis of 2',3'-cAMP into 3'-AMP is nonspecific. Modeling of 2',3'-cyclic nucleotide into the active site of a EAL domain PDE, overview
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
-
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
-
activity resides in the C-terminus
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
-
His-230 and His-309 of CNP1 play critical roles in enzyme catalysis, no essential role of cysteines, the catalytic domain forms a compact globular structure
-
ir
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
-
plays a role in cytoskeletal rearrangement, cell morphology and cell process outgrowth, increased expression of CNP is a marker for oligodendrocyte development
-
?
additional information
?
-
-
CNP acts as microtubule-associated protein in promoting microtubule assembly at low mole ratios, links tubulin to membranes and may regulate cytoplasmic microtubule distribution, membrane anchor for tubulin
-
?
additional information
?
-
-
CNP is one of the earliest myelin-related proteins to be expressed in differentiated oligodendrocytes and Schwann cells, role in migration and/or expansion of membranes during myelination
-
?
additional information
?
-
-
CNP performs an integral role in myelinogenesis, both isoforms likely play complementary roles in the onset of process outgrowth and ultimately myelination of axons
-
?
additional information
?
-
-
early oligodendroglial marker, CNPase links myelin related proteins to the cytoskeleton also interacting with membrane lipids during extension and wrapping of the oligodendroglial process around the axon, in mature myelinated fiber the CNPase is absent from compact myelin sheath, being located only in the inner and outer loops and in paranodal loops
-
?
additional information
?
-
-
myelin-specific protein, synthesized by oligodendrocytes, more abundant in the myelin of the CNS than in that of the peripheral nervous system, CNP is regulated by several protein kinases and may have a role in morphological changes of the cells by modulating the cytoskeleton
-
?
additional information
?
-
-
non-compact myelin protein, may have a unique role in signaling pathways mediated by lipid-protein domains
-
?
additional information
?
-
-
related to axonal ensheathment by myelinating cells
-
?
additional information
?
-
-
the cAMP-mediated pathway is part of the molecular mechanisms regulating the expression of CNP1 in oligodendrocytes, roles of AP-2, AP-4, nuclear factor-1 and protein kinase A in the regulation of CNP1 expression
-
?
additional information
?
-
-
endogenous enzyme expression is augmented by juxtanodin transfection, an oligodendroglial protein that promotes cellular arborization. Juxtanodin also augments transport of enzyme to the process arbors of cultured primary oligodendrocyte precursors
-
-
?
additional information
?
-
-
enzyme can perform the essential 3'-end-healing steps of tRNA splicing in yeast and complement growth of strains bearing lethal or temperature-sensitive mutations in the tRNA ligase 3'-end-healing domain
-
-
?
additional information
?
-
-
enzyme binds purine nucleotide triphosphates with an affinity higher than that displayed for diphosphates, while the affinity for both purine monophosphates and pyrimidine nucleotides is negligible. Analysis of binding constants for GTP, GDP, GMP, ATP, ADP, CTP, CDP, UTP, UDP
-
-
?
additional information
?
-
-
CNP is an RNA-binding protein, CNP associates with poly(A)+ mRNAs in vivo and suppresses translation in vitro in a dose-dependent manner, isoform CNP1 may regulate expression of mRNAs in oligodendrocytes of the central nervous system
-
-
?
additional information
?
-
-
substrate specificities and activities of RocR, DGC2, YybT, YtqI, 3DMA, and PaAcpH with 2',3'-cAMP, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
-
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
-
plays a role in cytoskeletal rearrangement, cell morphology and cell process outgrowth, increased expression of CNP is a marker for oligodendrocyte development
-
?
additional information
?
-
-
CNP acts as microtubule-associated protein in promoting microtubule assembly at low mole ratios, links tubulin to membranes and may regulate cytoplasmic microtubule distribution, membrane anchor for tubulin
-
?
additional information
?
-
-
CNP is one of the earliest myelin-related proteins to be expressed in differentiated oligodendrocytes and Schwann cells, role in migration and/or expansion of membranes during myelination
-
?
additional information
?
-
-
CNP performs an integral role in myelinogenesis, both isoforms likely play complementary roles in the onset of process outgrowth and ultimately myelination of axons
-
?
additional information
?
-
-
early oligodendroglial marker, CNPase links myelin related proteins to the cytoskeleton also interacting with membrane lipids during extension and wrapping of the oligodendroglial process around the axon, in mature myelinated fiber the CNPase is absent from compact myelin sheath, being located only in the inner and outer loops and in paranodal loops
-
?
additional information
?
-
-
myelin-specific protein, synthesized by oligodendrocytes, more abundant in the myelin of the CNS than in that of the peripheral nervous system, CNP is regulated by several protein kinases and may have a role in morphological changes of the cells by modulating the cytoskeleton
-
?
additional information
?
-
-
non-compact myelin protein, may have a unique role in signaling pathways mediated by lipid-protein domains
-
?
additional information
?
-
-
related to axonal ensheathment by myelinating cells
-
?
additional information
?
-
-
the cAMP-mediated pathway is part of the molecular mechanisms regulating the expression of CNP1 in oligodendrocytes, roles of AP-2, AP-4, nuclear factor-1 and protein kinase A in the regulation of CNP1 expression
-
?
additional information
?
-
-
endogenous enzyme expression is augmented by juxtanodin transfection, an oligodendroglial protein that promotes cellular arborization. Juxtanodin also augments transport of enzyme to the process arbors of cultured primary oligodendrocyte precursors
-
-
?
additional information
?
-
-
enzyme can perform the essential 3'-end-healing steps of tRNA splicing in yeast and complement growth of strains bearing lethal or temperature-sensitive mutations in the tRNA ligase 3'-end-healing domain
-
-
?
additional information
?
-
-
CNP is an RNA-binding protein, CNP associates with poly(A)+ mRNAs in vivo and suppresses translation in vitro in a dose-dependent manner, isoform CNP1 may regulate expression of mRNAs in oligodendrocytes of the central nervous system
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
Ca2+-stimulated and permeability transition pore-associated enzyme phosphorylation
additional information
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1,3-dipropyl-8-(4-sulfophenyl)xanthine
-
41% inhibition at 1 mM, 75% inhibition at 10 mM
5,5'-dithiobis-(2-nitrobenzoic acid)
-
97% inhibition of the catalytic fragment of CNP1 in a time- and dose-dependent manner, kinetics, fully reversed by excess dithiothreitol or 2-mercaptoethanol, inhibition is attributable to steric effects of modification of Cys-236 and Cys-314 by the inhibitor
diethylpyrocarbonate
-
pH 6.5, 22°C, time-dependent inhibition, kinetics, completely reversed by 0.5 M hydroxylamine
lead
-
90 days exposure of young adult rats to lead in drinking water, decrease both in enzyme protein content and activity
methyl methanethiosulfonate
-
42% inhibition of the catalytic fragment of CNP1
additional information
-
actinomycin D or cycloheximide completely inhibits the dibutyryl-cAMP-induced accumulation of CNP1 mRNA
-
additional information
-
effect of ethanol on the activity and expression of CNP isoenzymes, ethanol does not alter the developmentally regulated increased expression of CNP isoenzymes or enzyme activity
-
additional information
-
hypothyroidism impairs transiently the CNPase gene expression, rats receiving methimazol during gestation or postnatally show a delay in CNPase expression followed by a decrease in the number of CNPase immunoreactive fibers
-
additional information
-
no effect on enzyme activity by calmodulin binding
-
additional information
-
not inhibited by 1 mM 3-isobutyl-1-methylxanthine
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
lipopolysaccharide
-
enzyme expression is significantly up-regulated in microglial activation induced in vitro by lipopolysaccharide
additional information
-
up-regulation of CNP1 expression compared with CMP2 expression by cAMP or its analogues, e.g. dibutyryl-cAMP, in C6 cells
-
additional information
-
no effect on enzyme activity by calmodulin binding
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.295
2',3'-cNADP
-
pH 6, 25°C, catalytic fragment of CNP1 corresponding to the C-terminal 250 amino acids
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1690
2',3'-cNADP
-
pH 6, 25°C, catalytic fragment of CNP1 corresponding to the C-terminal 250 amino acids
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
mitochondrial inner and outer membrane, effect of chronic ethanol ingestion
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
presence of enzyme immunoreactive material at birth, progressive reduction with age with complete loss at postnatal day 18
-
cerebellar postsynaptic density fraction, both isoforms CNP1 and CNP2 are expressed in cerian populations of cerebellar cells, in oligodendrocytes, Purkinje cells and unidentified PSD95-positive cells, not in granule cells
-
presence of enzyme immunoreactive material at birth, progressive reduction with age with complete loss at postnatal day 18
-
ATCC CRL 8305, thyroid cells, CNP is firmly associated with FRTL-5 cells
-
presence of enzyme immunoreactive material at birth, progressive reduction with age with complete loss at postnatal day 18
additional information
-
-
135380, 135381, 135399, 135401, 135404, 135407, 135418, 135419, 135422, 729185, 729954, 730238, 730475, 751698
-
CNPase expression pattern of brain tissues in hypothyroid and control rats from post-natal days 5 to 90, hypothyroidism impairs transiently the CNPase gene expression, effect on oligodendrocyte differentiation and myelination
-
subventricular zone rostral extension, CNPase expression pattern during development from postnatal day 3 to 60
-
there is little CNP2 in the forebrain postsynaptic density fraction, CNP1 is the major isoform in the neural and non-neural rat tissues, with the exception of myelinating cells in the adult brain, in which both isoforms are highly expressed, CNP2 is barely detectable in embryonic brain
-
oligodendrocyte-enriched cultures of neonatal rat brain glial cells, CNP2
-
the enzyme is a quantitatively major enzyme in myelin, where it localizes to the non-compact regions and is bound to the membrane surface
-
the enzyme is one of the most abundant proteins in CNS myelin
-
developing, detailed CNPase expression pattern during development from postnatal day 3 to 60, expression follows a general caudorostral gradient, with the exception of the glomerular layer
-
the two isoforms CNP1 and CNP2 are differentially regulated during the process of maturation, CNP expression pattern
-
myelinating, colocalization of CNPase and CaM during Schwann cell myelination in culture
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
tubulin from brain, microtubule-associated protein, membrane anchor for tubulin, membrane-bound
additional information
-
along the cytoplasmic boundaries of the normal oligodendroglia. Mild to moderate anti-CNPase staining extends to the swollen cytoplasm of the oligodendroglia in aniline-treated rats from day 2 to day 4
-
integral membrane protein, inner and outer mitochondrial membrane
-
membrane-bound, microtubule-associated protein, membrane anchor for tubulin
-
a 13 residue C-terminal fragment is responsible for enzyme membrane anchoring. Lipidation of the 13 residue fragment is essential for the peptide to be folded and correctly positioned on the membrane surface
-
enzyme contains a mitochondrial targeting signal at the N-terminus. Import to mitochondria leads to cleavage of signal sequence yielding a mature, truncated form of CNP2 similar in size as CNP1. CNP2 is localized specifically to mitochondria in non-myelinating cells, e.g. in adult liver or embryonic brain. Phosphorylation of the signal sequence by protein kinase C inhibits translocation to mitochondria.
-
distribution of isozymes in mitochondrial fractions, i.e. myelin fraction, synaptic and nonsynaptic mitochondria, obtained after separation of brain mitochondria
-
the enzyme is associated with complexes I-V in mitochondria
additional information
-
the enzyme binds to calmodulin in a Ca2+-dependent manner via its binding site in the N-terminal domain, colocalization of CNPase and CaM during Schwann cell myelination in culture, molecular modeling
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
evolution
-
the catalytic domain is composed of about 240 amino acids, is highly conserved in mammals, and is present in all identified enzymes throughout different organisms
malfunction
-
truncations after amino acid 164 in recombinant rat enzyme result in a loss of phosphodiesterase activity
metabolism
-
the enzyme is involved in the regulation of the kinases Akt and GSK3beta
physiological function
additional information
physiological function
melatonin retains the enzyme inside mitochondria, thereby providing the protection of the protein against deleterious effects of 2',3'-cAMP in aging
physiological function
the enzyme interacts with microtubules and promotes tubulin polymerization
physiological function
-
Ca2+-stimulated and permeability transition pore-associated enzyme phosphorylation might be an important stage of permeability transition pore regulation in mitochondria, revealing an additional function of CNPase outside of myelin structure
physiological function
-
the enzyme encoding gene may play an important role as a putative anti-inflammatory gene both in normal and injured brain
physiological function
-
the enzyme interacts with membrane surfaces, cytoskeletal proteins, and calmodulin
physiological function
-
the enzyme is involved in regulation of the nonspecific pore, addition of myelin fraction associated with brain mitochondria to the suspension of liver mitochondria can lead to binding of the enzyme and myelin basic protein, present in the fraction with liver mitochondria under the conditions of both closed and opened permeability transition pore
additional information
-
role for the N-terminal domain of the enzyme in mediating multiple molecular interactions, molecular modeling, overview
additional information
-
structure of the CNPase phosphodiesterase domain and its catalytic mechanism, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). CN37_RAT
420
0
47268
Swiss-Prot
Mitochondrion (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
100000
-
gel filtration and gel electrophoresis under non reducing conditions, sucrose density gradient centrifugation
46000
48000
46000
-
x * 48000, CNP2, x * 46000, CNP1, SDS-PAGE, under non-reducing conditions, composed of mixed subunits, ratio CNP2/CNP1 ranging from 2:1 in bovine to 1:10 in mouse and rat
48000
-
x * 48000, CNP2, x * 46000, CNP1, SDS-PAGE, under non-reducing conditions, composed of mixed subunits, ratio CNP2/CNP1 ranging from 2:1 in bovine to 1:10 in mouse and rat
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
dimer
-
x * 48000, CNP2, x * 46000, CNP1, SDS-PAGE, under non-reducing conditions, composed of mixed subunits, ratio CNP2/CNP1 ranging from 2:1 in bovine to 1:10 in mouse and rat
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
lipoprotein
-
a 13 residue C-terminal fragment is responsible for enzyme membrane anchoring. Lipidation of the 13 residue fragment is essential for the peptide to be folded and correctly positioned on the membrane surface
phosphoprotein
proteolytic modification
-
enzyme contains a mitochondrial targeting signal at the N-terminus. Import to mitochondria leads to cleavage of signal sequence yielding a mature, truncated form of CNP2 similar in size as CNP1. Phosphorylation of the signal sequence by protein kinase C inhibits translocation to mitochondria.
side-chain modification
phosphoprotein
-
both isoforms CNP1 and CNP2 are tyrosine-phosphorylated to a basal extend
phosphoprotein
-
CNP is phosphorylated in vivo by protein kinase C, phosphorylation of CNP1 interferes with its microtubule assembly-promoting activity
phosphoprotein
-
only CNP2 is phosphorylated in vivo, CNP1 not, Ser-9 of CNP2 is phosphorylated by a 4-beta-phorbol 12,13-dibutyrate-sensitive kinase, likely protein kinase C, and Ser-22 appears to be constitutively phosphorylated, phosphorylation of Ser-9 may provide a molecular switching mechanism for modulating the function of CNP2 distinguishing it functionally from CNP1
phosphoprotein
-
Ca2+-stimulated and permeability transition pore-associated enzyme phosphorylation on Ser and Thr residues. Permeability transition pore inducer Atr is able to stimulate the ATP incorporation into 46 kDa enzyme in the presence of threshold Ca2+, whereas CsA suppresses significantly phosphorylation of the enzyme
phosphoprotein
-
two phosphorylation sites on Tyr110 and Ser169 within the N-terminal domain
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
modeling of enzyme N-terminal region and simulation of docking of nucleotides
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H230F
-
almost inactive CNP1 catalytic fragment mutant with 1000fold lower kcat-value and similar Km-value compared with wild-type CNP1
H230L
-
almost inactive CNP1 catalytic fragment mutant with 1000fold lower kcat-value and similar Km-value compared with wild-type CNP1
H309F
-
almost inactive CNP1 catalytic fragment mutant with 1000fold lower kcat-value and similar Km-value compared with wild-type CNP1
H309L
-
almost inactive CNP1 catalytic fragment mutant with 1000fold lower kcat-value and similar Km-value compared with wild-type CNP1
additional information
additional information
-
C-terminal deletion of 13 amino acids of CNP1 leads to an abnormal microtubule distribution in the cell
additional information
-
CNP1: N-terminal deletion mutants, catalytic fragment corresponding to the last C-terminal 250 amino acids
additional information
-
expression of enzyme in yeast can complement growth of strains bearing lethal or temperature-sensitive mutations in the tRNA ligase 3'-end-healing domain
additional information
-
CNP-CF is a CNP1 deletion mutant lacking the first 150 amino acids
additional information
-
generation of inactive mutants truncated after amino acid 164
additional information
-
generation of truncated enzyme mutants: CNP_20-398, CNP_25-398, CNP_20-420, CNP_20-185, and CNP_179-398, analysis of calmodulin binding activity
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ethanol
-
at a final concentration up to 4% v/v of the total volume, no effect on CNP1 activity
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged wild-type full-length enzyme and truncated mutants by nickel affinity chromatography and gel filtration or by calmodulin affinity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
full-length CNP1 and C-terminal deletion mutant, fused to glutathione S-transferase, expression in Escherichia coli JM83, fused to green fluorescent protein, expression in COS-7 cells
-
recombinant expression of His-tagged wild-type full-length enzyme and truncated mutants
-
wild type and mutant CNP proteins are produced in vitro in rabbit reticulocyte lysate in the presence of S-methionine
-
wild-type and mutant CNP2, expression in 293T human kidney fibroblast cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme expression is upregulated in activated microglia as a response to brain injury
after treatment with a single dose of aniline at 1000 mg/kg, expression of CNPase increases from day 2 and peaks on days 3 and 4
-
after treatment with a single dose of aniline at 1000 mg/kg, spongy change in the spinal cord from day 5, after which CNPase expression decreases remarkably
-
markedly enhanced enzyme expression, CNPase protein and mRNA expression, in microglia after activation by lipopolysaccharide treatment
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
cells derived from transplanted marrow stromal cells can transform into cells resembling Schwann cells, whereas host-derived glial cells participate in formation of perineural compartments. The chemotactic migration of both host-derived and transplantation-derived cells bearing the enzyme in their plasma membrane may be attracted by stromal derived factor-1alpha produced locally
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sprinkle, T.J.
2'3'-cyclic nucleotide 3'-phosphodiesterase, an oligodendrocyte-Schwann cell and myelin-associated enzyme of the nervous system
CRC Crit. Rev. Clin. Neurobiol.
4
235-301
1989
Bos taurus, Canis lupus familiaris, Cavia porcellus, Gallus gallus, Oryctolagus cuniculus, Chondrichthyes, Haemophilus influenzae, Ovis aries, Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa, Xenopus laevis
Vogel, U.S.; Thompson, R.J.
Molecular structure, localization, and possible functions of the myelin-associated enzyme 2,3-cyclic nucleotide 3-phosphodiesterase
J. Neurochem.
50
1667-1677
1988
Bos taurus, Gallus gallus, Chondrichthyes, Homo sapiens, Rattus norvegicus, Xenopus laevis
Dreiling, C.E.; Schilling, R.J.; Reitz, R.C.
2,3-cyclic nucleotide 3-phosphohydrolase in rat liver mitochondrial membranes
Biochim. Biophys. Acta
640
114-120
1981
Rattus norvegicus
Lin, L.F.H.; Bartlett, C.; Lees, M.B.
Preparation and characterization of unilamellar myelin vesicles
J. Biol. Chem.
261
16241-16246
1986
Rattus norvegicus
Blair, G.E.; Sawecka, J.; Griffiths, S.A.; Blair Zajdel, M.E.
Biosynthesis of 2',3'-cyclic nucleotide 3'-phosphodiesterase (Wolfgram proteins) in rat brain and glioma cells
Biochem. Soc. Trans.
16
212-213
1988
Rattus norvegicus
-
Prohaska, J.R.; Clark, D.A.; Wells, W.W.
Improved rapidity and precision in the determination of brain 2',3'-cyclic nucleotide 3-phosphohydrolase
Anal. Biochem.
56
275-282
1973
Gallus gallus, Mus musculus, Rattus norvegicus
Waehneldt, T.V.
Ontogenetic study of a myelin-derived fraction with 2':3'-cyclic nucleotide 3'-phosphohydrolase activity higher than that of myelin
Biochem. J.
151
435-437
1975
Rattus norvegicus
Dreiling, C.E.; Schilling, R.J.; Reitz, R.C.
Effects of chronic ethanol ingestion on the activity of rat liver mitochondrial 2',3'- cyclic nucleotide
Biochim. Biophys. Acta
640
121-130
1981
Rattus norvegicus
Craven, P.A.; Neidig, M.; De Rubertis, F.R.
Properties of multiple kinetic forms of soluble cyclic nucleotide phosphodiesterase activity of rat colonic mucosa
Biochim. Biophys. Acta
744
265-275
1983
Rattus norvegicus
Stricker, R.; Lottspeich, F.; Reiser, G.
The myelin protein CNP (2',3'-cyclic nucleotide 3'-phosphodiesterase): Immunoaffinity purification of CNP from pig and rat brain using a monoclonal antibody and phosphorylation of CNP by cyclic nucleotide-dependent protein kinases
Biol. Chem. Hoppe-Seyler
375
205-209
1994
Rattus norvegicus, Sus scrofa
Fressinaud, C.; Sarlieve, L.L.; Dalencon, D.; Labourdette, G.
Differential regulation of cerebroside sulfotransferase and 2',3'-cyclic nucleotide 3'-phosphodiesterase by basic fibroblast growth factor in relation to proliferation in rat oligodendrocyte cultures
J. Cell. Physiol.
150
34-44
1992
Rattus norvegicus
Braun, P.E.; Bambrick, L.L.; Edwards, A.M.; Bernier, L.
2',3'-cyclic-nucleotide 3'- phosphodiesterase has characteristics of cytoskeletal proteins. A hypothesis for its function
Ann. N. Y. Acad. Sci.
605
55-65
1990
Bos taurus, Rattus norvegicus
Gravel, M.; DeAngelis, D.; Braun, P.E.
Molecular cloning and characterization of rat brain 2',3'-phosphodiesterase isoform 2
J. Neurosci. Res.
38
243-247
1994
Rattus norvegicus
Bichenkov, E.; Ellingson, J.S.
Ethanol exerts different effects on myelin basic protein and 2',3'-cyclic nucleotide 3'-phosphodiesterase expression in differentiating CG-4 oligodendrocytes
Brain Res. Dev. Brain Res.
128
9-16
2001
Rattus norvegicus
Barradas, P.C.; Ferraz, A.S.; Ferreira, A.A.; Daumas, R.P.; Moura, E.G.
2'3'Cyclic nucleotide 3'phosphodiesterase immunohistochemistry shows an impairment on myelin compaction in hypothyroid rats
Int. J. Dev. Neurosci.
18
887-892
2000
Rattus norvegicus
Lee, J.; Gravel, M.; Gao, E.; O'Neill, R.C.; Braun, P.E.
Identification of essential residues in 2',3'-cyclic nucleotide 3'-phosphodiesterase. Chemical modification and site-directed mutagenesis to investigate the role of cysteine and histidine residues in enzymatic activity
J. Biol. Chem.
276
14804-14813
2001
Rattus norvegicus
O'Neill, R.C.; Braun, P.E.
Selective synthesis of 2',3'-cyclic nucleotide 3'-phosphodiesterase isoform 2 and identification of specifically phosphorylated serine residues
J. Neurochem.
74
540-546
2000
Rattus norvegicus
Gravel, M.; Gao, E.; Hervouet-Zeiber, C.; Parsons, V.; Braun, P.E.
Transcriptional regulation of 2',3'-cyclic nucleotide 3'-phosphodiesterase gene expression by cyclic AMP in C6 cells
J. Neurochem.
75
1940-1950
2000
Mus musculus, Rattus norvegicus
Gomes, S.S.; Carvalho, S.L.; Santiago, M.F.; Lopez, L.B.; Barradas, P.C.; Cavalcante, L.A.
Expression of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in the developing olfactory bulb and subventricular zone rostral extension
J. Neurosci. Res.
73
471-480
2003
Rattus norvegicus
Cho, S.J.; Jung, J.S.; Jin, I.; Moon, I.S.
2', 3'-cyclic nucleotide 3'-phosphodiesterase is expressed in dissociated rat cerebellar cells and included in the postsynaptic density fraction
Mol. Cells
16
128-135
2003
Rattus norvegicus
Santos-Silva, A.; Cavalcante, L.A.
Expression of the non-compact myelin protein 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in olfactory bulb ensheathing glia from explant cultures
Neurosci. Res.
40
189-193
2001
Rattus norvegicus
Bifulco, M.; Laezza, C.; Stingo, S.; Wolff, J.
2',3'-Cyclic nucleotide 3'-phosphodiesterase: A membrane-bound, microtubule-associated protein and membrane anchor for tubulin
Proc. Natl. Acad. Sci. USA
99
1807-1812
2002
Rattus norvegicus
Dabrowska-Bouta, B.; Sulkowski, G.; Struzynska, L.; Rafalowska, U.
CNPase activity in myelin from adult rat brains after prolonged lead exposure in vivo
Chem. Biol. Interact.
150
171-178
2004
Rattus norvegicus
Lee, J.; O'Neill, R.C.; Park, M.W.; Gravel, M.; Braun, P.E.
Mitochondrial localization of CNP2 is regulated by phosphorylation of the N-terminal targeting signal by PKC: implications of a mitochondrial function for CNP2 in glial and non-glial cells
Mol. Cell. Neurosci.
31
446-462
2006
Rattus norvegicus
Zhang, B.; Cao, Q.; Guo, A.; Chu, H.; Chan, Y.G.; Buschdorf, J.P.; Low, B.C.; Ling, E.A.; Liang, F.
Juxtanodin: an oligodendroglial protein that promotes cellular arborization and 2',3'-cyclic nucleotide-3'-phosphodiesterase trafficking
Proc. Natl. Acad. Sci. USA
102
11527-11532
2005
Rattus norvegicus
Esposito, C.; Scrima, M.; Carotenuto, A.; Tedeschi, A.; Rovero, P.; DErrico, G.; Malfitano, A.M.; Bifulco, M.; DUrsi, A.M.
Structures and micelle locations of the nonlipidated and lipidated C-terminal membrane anchor of 2',3'-cyclic nucleotide-3'-phosphodiesterase
Biochemistry
47
308-319
2008
Rattus norvegicus
Stingo, S.; Masullo, M.; Polverini, E.; Laezza, C.; Ruggiero, I.; Arcone, R.; Ruozi, E.; Dal Piaz, F.; Malfitano, A.M.; DUrsi, A.M.; Bifulco, M.
The N-terminal domain of 2,3-cyclic nucleotide 3-phosphodiesterase harbors a GTP/ATP binding site
Chem. Biol. Drug Des.
70
502-510
2007
Rattus norvegicus
Cao, Q.; Ding, P.; Lu, J.; Dheen, S.T.; Moochhala, S.; Ling, E.A.
2',3'-Cyclic nucleotide 3'-phosphodiesterase cells derived from transplanted marrow stromal cells and host tissue contribute to perineurial compartment formation in injured rat spinal cord
J. Neurosci. Res.
85
116-130
2007
Rattus norvegicus
Wu, C.Y.; Lu, J.; Cao, Q.; Guo, C.H.; Gao, Q.; Ling, E.A.
Expression of 2,3-cyclic nucleotide 3-phosphodiesterase in the amoeboid microglial cells in the developing rat brain
Neuroscience
142
333-341
2006
Rattus norvegicus
Schwer, B.; Aronova, A.; Ramirez, A.; Braun, P.; Shuman, S.
Mammalian 2,3 cyclic nucleotide phosphodiesterase (CNP) can function as a tRNA splicing enzyme in vivo
RNA
14
204-210
2008
Rattus norvegicus
Gravel, M.; Robert, F.; Kottis, V.; Gallouzi, I.E.; Pelletier, J.; Braun, P.E.
2,3-Cyclic nucleotide 3-phosphodiesterase: a novel RNA-binding protein that inhibits protein synthesis
J. Neurosci. Res.
87
1069-1079
2009
Rattus norvegicus
Kanno, T.; Kurotaki, T.; Yamada, N.; Yamashita, K.; Wako, Y.; Tsuchitani, M.
Activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in spinal cord with spongy change induced by a single oral dose of aniline in rats
Toxicol. Pathol.
38
359-365
2010
Rattus norvegicus
Rao, F.; Qi, Y.; Murugan, E.; Pasunooti, S.; Ji, Q.
2',3'-cAMP hydrolysis by metal-dependent phosphodiesterases containing DHH, EAL, and HD domains is non-specific: implications for PDE screening
Biochem. Biophys. Res. Commun.
398
500-505
2010
Rattus norvegicus
Baburina, Y.L.; Gordeeva, A.E.; Moshkov, D.A.; Krestinina, O.V.; Azarashvili, A.A.; Odinokova, I.V.; Azarashvili, T.S.
Interaction of myelin basic protein and 2',3'-cyclic nucleotide phosphodiesterase with mitochondria
Biochemistry (Moscow)
79
555-565
2014
Rattus norvegicus, Rattus norvegicus Wistar
Azarashvili, T.; Krestinina, O.; Galvita, A.; Grachev, D.; Baburina, Y.; Stricker, R.; Reiser, G.
Identification of phosphorylated form of 2, 3-cyclic nucleotide 3-phosphodiesterase (CNPase) as 46kDa phosphoprotein in brain non-synaptic mitochondria overloaded by calcium
J. Bioenerg. Biomembr.
46
135-145
2014
Rattus norvegicus
Myllykoski, M.; Itoh, K.; Kangas, S.M.; Heape, A.M.; Kang, S.U.; Lubec, G.; Kursula, I.; Kursula, P.
The N-terminal domain of the myelin enzyme 2',3'-cyclic nucleotide 3'-phosphodiesterase: direct molecular interaction with the calcium sensor calmodulin
J. Neurochem.
123
515-524
2012
Mus musculus, Rattus norvegicus
Yang, L.; Kan, E.M.; Lu, J.; Wu, C.; Ling, E.A.
Expression of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and its roles in activated microglia in vivo and in vitro
J. Neuroinflammation
11
148
2014
Mus musculus, Rattus norvegicus, Rattus norvegicus Sprague-Dawley, Rattus norvegicus Wistar
Raasakka, A.; Kursula, P.
The myelin membrane-associated enzyme 2',3'-cyclic nucleotide 3'-phosphodiesterase: on a highway to structure and function
Neurosci. Bull.
30
956-966
2014
Oryctolagus cuniculus, Homo sapiens, Mus musculus, Rattus norvegicus
Baburina, Y.; Odinokova, I.; Azarashvili, T.; Akatov, V.; Lemasters, J.J.; Krestinina, O.
2',3'-Cyclic nucleotide 3'-phosphodiesterase as a messenger of protection of the mitochondrial function during melatonin treatment in aging
Biochim. Biophys. Acta
1859
94-103
2017
Rattus norvegicus (P13233)
Myllykoski, M.; Seidel, L.; Muruganandam, G.; Raasakka, A.; Torda, A.E.; Kursula, P.
Structural and functional evolution of 2',3'-cyclic nucleotide 3'-phosphodiesterase
Brain Res.
1641
64-78
2016
Rattus norvegicus (P13233), Mus musculus (P16330)
Baburina, Y.; Odinokova, I.; Azarashvili, T.; Akatov, V.; Sotnikova, L.; Krestinina, O.
Possible involvement of 2',3'-cyclic nucleotide-3'-phosphodiesterase in the protein phosphorylation-mediated regulation of the permeability transition pore
Int. J. Mol. Sci.
19
E3499
2018
Rattus norvegicus
Verrier, J.D.; Kochanek, P.M.; Jackson, E.K.
Schwann cells metabolize extracellular 2',3'-cAMP to 2'-AMP
J. Pharmacol. Exp. Ther.
354
175-183
2015
Rattus norvegicus
Baburina, Y.; Azarashvili, T.; Grachev, D.; Krestinina, O.; Galvita, A.; Stricker, R.; Reiser, G.
Mitochondrial 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) interacts with mPTP modulators and functional complexes (I-V) coupled with release of apoptotic factors
Neurochem. Int.
90
46-55
2015
Rattus norvegicus
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