Information on EC 3.1.4.37 - 2',3'-cyclic-nucleotide 3'-phosphodiesterase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
3.1.4.37
-
RECOMMENDED NAME
GeneOntology No.
2',3'-cyclic-nucleotide 3'-phosphodiesterase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
nucleoside 2',3'-cyclic phosphate + H2O = nucleoside 2'-phosphate
show the reaction diagram
-
-
-
-
nucleoside 2',3'-cyclic phosphate + H2O = nucleoside 2'-phosphate
show the reaction diagram
catalytic mechanism
-
nucleoside 2',3'-cyclic phosphate + H2O = nucleoside 2'-phosphate
show the reaction diagram
general acid/general base catalysis by H310, H231 and a water molecule, mechanism
-
nucleoside 2',3'-cyclic phosphate + H2O = nucleoside 2'-phosphate
show the reaction diagram
during catalytic mechanism, a 2',3'-cyclic nucleotide is converted into a 2'-nucleotide through a nucleophilic attack carried out by an activated water molecule, dinucleotide binding mode, overview
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
hydrolysis of phosphoric ester
P06961
-
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.
SYNONYMS
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'-phosphodiesterase
-
-
2',3'-cyclic nucleotide 3'-phosphodiesterase
-
-
2',3'-cyclic nucleotide 3'-phosphodiesterase
P09543
-
2',3'-cyclic nucleotide 3'-phosphodiesterase
-
-
2',3'-cyclic nucleotide 3'-phosphodiesterase
-
-
2',3'-cyclic nucleotide 3'-phosphodiesterase
P16330
-
2',3'-cyclic nucleotide 3'-phosphodiesterase
-
-
2',3'-cyclic nucleotide 3'-phosphodiesterase
-
-
2',3'-cyclic nucleotide 3'-phosphodiesterase
Rattus norvegicus Sprague-Dawley
-
-
-
2',3'-cyclic nucleotide 3'-phosphodiesterase
Rattus norvegicus Wistar
-
;
-
2',3'-cyclic nucleotide 3'-phosphohydrolase
-
-
-
-
2',3'-cyclic nucleotide phosphodiesterase
-
-
2',3'-cyclic nucleotide phosphodiesterase
Rattus norvegicus Wistar
-
-
-
2',3'-cyclic nucleotide phosphohydrolase
-
-
-
-
2',3'-cyclic nucleotide-3'-phosphohydrolase
-
-
2',3'-cyclic phosphodiesterase
-
-
2',3'-cyclic-nucleotide 3'-phosphodiesterase type I
P09543
-
2':3'-CNMP-3'-ase
-
-
2':3'-cyclic nucleotide 3'-phosphodiesterase
-
-
-
-
CNP
-
-
-
-
CNP1
-
isoform
CNPase
-
-
-
-
CNPase
-
-
CNPase
P16330
-
CNPase
Rattus norvegicus Sprague-Dawley, Rattus norvegicus Wistar
-
-
-
CNPase I
P09543
-
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'-
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
60098-35-3
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
var. amyloliquefacus
-
-
Manually annotated by BRENDA team
overview, calf
-
-
Manually annotated by BRENDA team
overview
-
-
Manually annotated by BRENDA team
zebrafish
-
-
Manually annotated by BRENDA team
2',3'-cyclic phosphodiesterase activity of the C-terminal HD domain of the multifunctional enzyme tRNA nucleotidyltransferase, EC 2.7.7.25
-
-
Manually annotated by BRENDA team
isoforms CNP1 and CNP2
UniProt
Manually annotated by BRENDA team
overview
-
-
Manually annotated by BRENDA team
two isozymes, difference between the variants is the presence of a 20-amino-acid N-terminal mitochondrial targeting sequence in the 48-kDa isoform II, which is removed after mitochondrial import to produce a truncated 46-kDa variant that corresponds to the cytosolic isoform I of 400 amino-acids, gene CNP1
-
-
Manually annotated by BRENDA team
2 isoforms: CNP1 and CNP2
-
-
Manually annotated by BRENDA team
isoform 2
-
-
Manually annotated by BRENDA team
overview
-
-
Manually annotated by BRENDA team
no activity in Rattus norvegicus
in olfactory ensheathing cells
-
-
Manually annotated by BRENDA team
overview
-
-
Manually annotated by BRENDA team
bullfrog
-
-
Manually annotated by BRENDA team
2 isoenzymes of 46 and 48 kDa
-
-
Manually annotated by BRENDA team
2 isoforms: CNP1 and CNP2 differing by a 20-amino acid extension at the N-terminus
-
-
Manually annotated by BRENDA team
2 isoforms: CNP1 and CNP2, encoded by a single gene
-
-
Manually annotated by BRENDA team
isoform 2
-
-
Manually annotated by BRENDA team
isoform CNP2 fused to GFP
-
-
Manually annotated by BRENDA team
Sprague-Dawley rats, 1-2 days old, 2 isoforms: CNP1 and CNP2 differing by a 20-amino acid extension exclusive to CNP2
-
-
Manually annotated by BRENDA team
Sprague-Dawley rats, adult, 2 isoforms: CNP1 and CNP2, produced by ribosome initiation at different AUG codons
-
-
Manually annotated by BRENDA team
three-week-old male Crl:CD (SD) IGS rats
-
-
Manually annotated by BRENDA team
Wistar and Lister strains, age ranging from postnatal day 3 to 60
-
-
Manually annotated by BRENDA team
Wistar rats, 2 months old
-
-
Manually annotated by BRENDA team
Wistar rats, from post-natal days 5 to 90, hypothyroid and controls
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
Rattus norvegicus Wistar
-
-
-
Manually annotated by BRENDA team
polynucleotide kinase-phosphatase
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
evolution
-
the enzyme is a unique member of the 2H phosphoesterase family. 2H phosphoesterases differ in their respective reaction mechanisms despite the conserved catalytic residues. The HxS/Tx motifs of the catalytic phosphodiesterase domain are conserved throughout species, domains structure comparison, overview. Conservation of ligand-binding residues
evolution
-
the enzyme is a unique member of the 2H phosphoesterase family. Large differences in the active-site vicinity are observed when comparing more distant members of the 2H family
malfunction
-
a C-terminally truncated variant of CNPase, as well as a mutant unable to membrane-associate, are affected in oligodendrocyte process outgrowth, formation and branching
malfunction
-
changes in enzyme expression levels are linked to Alzheimer's disease, Down's syndrome, and catatonia-depression syndrome. A single-nucleotide polymorphism that does not alter the amino-acid sequence of the enzyme, but rather decreases its expression levels, has been suggested to play a role in schizophrenia
malfunction
-
inducible nitric oxide synthase, IL-1beta, TNF-alpha, reactive oxygen species and nitric oxide are significantly upregulated in activated BV-2 cells with CNPase enzyme knockdown. siRNA knockdown of the enzyme increases microglia migration, on the other hand, microglial cells appear to be arrested at G1 phase
malfunction
P09543
knockdown of the enzyme expression moderately improves hepatitis B viral production in the HepG2.2.15 cells treated with IFN-alpha
malfunction
-
truncations after amino acid 164 in recombinant rat enzyme result in a loss of phosphodiesterase activity
physiological function
-
an age-related impairment in proteasomal proteolysis and subsequent accumulation of ubiquitinated CNP activates alternative proteolytic mechanisms leading to CNP fragmentation
physiological function
-
an age-related impairment in proteasomal proteolysis and subsequent accumulation of ubiquitinated CNP activates alternative proteolytic mechanisms leading to CNP fragmentation. In the aged monkey, CNP is ubiquitinated and this ubiquitination can be found (at least in part) in detergent insoluble membrane microdomains
physiological function
-
incomplete degradation of CNP due to failure of the proteasomal system and aberrant degradation by calpain-1 leads to agerelated CNP accumulation and proteolysis. These phenomena result in age-related dysfunction of CNP in the lipid raft, which may lead to myelin and axonal pathology
physiological function
-
the CNP gene may not be involved in the etiology and pathology of schizophrenia in the Chinese Han population. No significant association between the two polymorphisms rs2070106 and rs8078650 and schizophrenia
physiological function
-
CNP is a cell type-specific marker of oligodendrocytes, has a physiological relevance to axon, myelin and oligodendrocytes, and acts as a conformational stabilizer for the intrinsically unstructured large segment of Amino-Nogo
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
-
in early stages of myelination, the enzyme is essential in oligodendrocyte process formation and branching, as well as for oligodendrocyte process outgrowth via its membrane association, as well as its ability to interact with the cytoskeleton. The role of CNPase after active myelination is related to axonal maintenance. Accumulation of 2',3'-cAMP is found in very young CNPase-deficient mice used to study traumatic brain injury, which develops post-traumatic axonal degeneration similar to that of older CNPase-deficient mice that do not experience brain trauma
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
physiological function
-
the enzyme is possible auto-antigen in multiple sclerosis. CNPase isoform II is responsible for mitochondrial import, which is regulated via phosphorylation by protein kinase C. The mitochondrial, fully-processed isoform II does not drive morphological differentiation in cell cultures as isoform I does in oligodendrocytes. The enzyme, together with 2',3'-cAMP, is suggested to modulate the mitochondrial permeability transition, a proapoptotic event, in which Ca2+ is released from the mitochondrial matrix to the intermembrane space and cytoplasm
physiological function
P09543
the enzyme might be a mediator of interferon-induced response against hepatitis B virus. Isozymes CNP1 and CNP2 potently inhibit hepatitis B virus production by blocking viral proteins synthesis and reducing viral RNAs, respectively. Inhibition by isozymes CNP1 and CNP2 appear to have distinct mechanism. In chronic hepatitis B patients, the enzyme is expressed in most of hepatitis B virus -infected hepatocytes of liver specimens. Because the enzyme targets the poly(A) of mRNA, it exhibited a nonspecific effect on protein synthesis
physiological function
Rattus norvegicus Sprague-Dawley
-
the enzyme encoding gene may play an important role as a putative anti-inflammatory gene both in normal and injured brain
-
physiological function
Rattus norvegicus Wistar
-
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, the enzyme encoding gene may play an important role as a putative anti-inflammatory gene both in normal and injured brain
-
metabolism
-
role of 2',3'-cyclic nucleotide 3'-phosphodiesterase in the renal 2',3'-cAMP-adenosine pathway, overview
additional information
-
binding mode of nucleotide ligands in the active site, structure-function analysis, catalytic mechanism, overview. Flexible loops might play roles in substrate recognition. The enzyme's N-terminal domain is involved in RNA binding and dimerization
additional information
-
role for the N-terminal domain of the enzyme in mediating multiple molecular interactions, molecular modeling, overview
additional information
-
structure of the 2'-cyclic AM-bound enzyme active site and its catalytic mechanism, overview
additional information
-
structure of the CNPase phosphodiesterase domain and its catalytic mechanism, overview
additional information
-
the enzyme shows an open/close motion of the beta5-alpha7 loop linked to the reaction. The two domains of the enzyme form an elongated molecule. The active site includes the two HxTx motifs on beta strands beta2 and beta5, between which lie four water molecules, forming the bottom of the active site. The N-terminus of helix alpha7, which is unique for the enzyme in the 2H family, plays a role during the reaction indicating that 2H phosphoesterases differ in their respective reaction mechanisms despite the conserved catalytic residues
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1,N6-etheno-2-azaadenosine-2',3'-cyclic monophosphate + H2O
etheno-2-azaadenosine-2'-monophosphate
show the reaction diagram
-
-
-
-
?
1,N6-ethenoadenosine-2',3'-cyclic monophosphate + H2O
ethenoadenosine-2'-monophosphate
show the reaction diagram
-
-
-
-
?
2', 3'-cyclic ribonucleotide
ribonucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
-
-
?
2',3'-cAMP + H2O
2'-AMP
show the reaction diagram
-
the protein consists of two domains: an uncharacterized N-terminal domain with little homology to other proteins, and a C-terminal phosphodiesterase domain. C-terminal tail (22 residues) has no significant effect on the catalytic activity, neither do the first 24 N-terminal residues of the full-length protein. Both the N- and C-terminal domain of recombinant CNPase are folded entities: N-terminal domain has more beta-sheet structure and less alpha-helices than the C-terminal domain
-
-
?
2',3'-cAMP + H2O
2'-AMP + 3'-AMP
show the reaction diagram
P06961
-
-
-
-
2',3'-cAMP + H2O
3'-AMP + ?
show the reaction diagram
-
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
-
-
?
2',3'-cCMP + H2O
2'-CMP
show the reaction diagram
-
-
-
-
?
2',3'-cCMP + H2O
2'-CMP
show the reaction diagram
-
-
-
-
?
2',3'-cCMP + H2O
2'-CMP
show the reaction diagram
-
-
-
-
?
2',3'-cCMP + H2O
2'-CMP
show the reaction diagram
-
-
-
-
?
2',3'-cCMP + H2O
2'-CMP
show the reaction diagram
-
-
-
-
?
2',3'-cCMP + H2O
2'-CMP
show the reaction diagram
-
-
-
-
?
2',3'-cGMP + H2O
2'-GMP
show the reaction diagram
-
-
-
-
?
2',3'-cGMP + H2O
2'-GMP
show the reaction diagram
-
-
-
-
?
2',3'-cGMP + H2O
2'-GMP
show the reaction diagram
-
-
-
-
?
2',3'-cGMP + H2O
2'-GMP
show the reaction diagram
-
-
-
-
?
2',3'-cGMP + H2O
2'-GMP
show the reaction diagram
-
-
-
-
?
2',3'-cGMP + H2O
2'-GMP + 3'-GMP
show the reaction diagram
P06961
-
-
-
-
2',3'-cNADP+ + H2O
2'-NADP+
show the reaction diagram
-
-
-
-
?
2',3'-cNADP+ + H2O
2'-NADP+
show the reaction diagram
-
-
-
?
2',3'-cNADP+ + H2O
2'-NADP+
show the reaction diagram
-
-
-
-
?
2',3'-cNADP+ + H2O
NADP+
show the reaction diagram
-
-
-
?
2',3'-cNADP+ + H2O
?
show the reaction diagram
P16330
-
-
-
?
2',3'-cUMP + H2O
2'-UMP
show the reaction diagram
-
-
-
-
?
2',3'-cUMP + H2O
2'-UMP
show the reaction diagram
-
-
-
-
?
2',3'-cUMP + H2O
2'-UMP
show the reaction diagram
-
-
-
-
?
2',3'-cUMP + H2O
2'-UMP
show the reaction diagram
-
-
-
-
?
2',3'-cyclic AMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cyclic AMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cyclic AMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cyclic AMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cyclic AMP + H2O
2'-AMP
show the reaction diagram
-
product binding structure, overview
-
-
?
2',3'-cyclic AMP + H2O
2'-AMP
show the reaction diagram
P16330
substrate and product enzyme binding structures, overview
-
-
?
2',3'-cyclic NADP+ + H2O
NADP+
show the reaction diagram
-
-
-
-
-
2',3'-cyclic NADP+ + H2O
NADP+
show the reaction diagram
-
-
-
?
2',3'-cyclic NADP+ + H2O
NADP+
show the reaction diagram
-
-
-
-
-
2',3'-cyclic-2-aza-e-AMP + H2O
2'-2-aza-e-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cyclic-e-AMP + H2O
2'-e-AMP
show the reaction diagram
-
-
-
-
?
2'-AMP + H2O
adenosine + phosphate
show the reaction diagram
P06961
-
-
-
-
3'-AMP + H2O
?
show the reaction diagram
-
-
-
-
?
adenosine 2,3-cyclic phosphorothioate + H2O
?
show the reaction diagram
P16330
the Sp epimer of 2',3'-cAMPS is a functional substrate for the enzyme, while the Rp epimer is not
-
-
?
ADP + H2O
AMP + phosphate
show the reaction diagram
P06961
-
-
-
-
ATP + H2O
ADP + phosphate
show the reaction diagram
P06961
-
-
-
-
bis(p-nitrophenyl)phosphate + H2O
?
show the reaction diagram
-
non-specific substrate
-
-
?
bis-p nitrophenyl phosphate + H2O
?
show the reaction diagram
-
-
-
-
?
bis-p-nitrophenyl phosphate + H2O
?
show the reaction diagram
P06961
-
-
?
CDP + H2O
CMP + phosphate
show the reaction diagram
P06961
-
-
-
-
CTP + H2O
CDP + phosphate
show the reaction diagram
P06961
-
-
-
-
cyclic 2',3'-AMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
cyclic 2',3'-AMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
cyclic 2',3'-AMP + H2O
2'-AMP
show the reaction diagram
P09543
-
-
-
?
cyclic 2',3'-AMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
cyclic 2',3'-AMP + H2O
2'-AMP
show the reaction diagram
P06961
best substrate
-
?
cyclic 2',3'-AMP + H2O
2'-AMP
show the reaction diagram
P06961
natural substrate, the 2',3'-cyclic phosphodiesterase activity of the C-terminal HD domain of tRNA nucleotidyltransferase, EC 2.7.7.25, is involved in the repair of the 3-CCA end of tRNA
-
?
cyclic 2',3'-CMP + H2O
2'-CMP
show the reaction diagram
P06961
low activity
-
?
cyclic 2',3'-GMP + H2O
2'-GMP
show the reaction diagram
P06961
high activity
-
?
NADP+ + H2O
NAD+ + phosphate
show the reaction diagram
P06961
-
-
-
-
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
P06961
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
P16330
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
activity resides in the C-terminus
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
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
show the reaction diagram
-
plays a role in cytoskeletal rearrangement, cell morphology and cell process outgrowth, increased expression of CNP is a marker for oligodendrocyte development
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
P16330
dinucleotide binding mode, overview
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
Rattus norvegicus Wistar
-
-
-
-
?
p-nitrophenyl phosphate + H2O
p-nitrophenol + phosphate
show the reaction diagram
P06961
-
-
-
-
diphosphate + H2O
2 phosphate
show the reaction diagram
P06961
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
not: 2',3'-cyclic esters in cyclic phosphate-terminated oligoribonucleotides or in nucleoside 5'-phosphate, 2',3'-cyclic phosphate
-
-
-
additional information
?
-
-
three enzyme forms
-
-
-
additional information
?
-
-
not: 3',5'-cyclic nucleotides
-
-
-
additional information
?
-
-
not: 3',5'-cyclic nucleotides
-
-
-
additional information
?
-
-
not: 3',5'-cyclic nucleotides
-
-
-
additional information
?
-
P06961
not: nucleoside 3',5'-cyclic phosphate
-
?
additional information
?
-
-
early stages of myelin formation
-
-
-
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 and nuclear factor-1 in the regulation of CNP1 expression
-
?
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 is involved in mediating process formation in oligodendrocytes
-
-
-
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
?
-
-
endogenous Nogo-A interacts with the endogenous CNP in vitro and in vivo
-
-
-
additional information
?
-
-
substrate specificities and activities of RocR, DGC2, YybT, YtqI, 3DMA, and PaAcpH with 2',3'-cAMP, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
2',3'-cyclic AMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cyclic AMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cyclic AMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
2',3'-cyclic AMP + H2O
2'-AMP
show the reaction diagram
-
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
P16330
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
-
-
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
-
plays a role in cytoskeletal rearrangement, cell morphology and cell process outgrowth, increased expression of CNP is a marker for oligodendrocyte development
-
?
nucleoside 2',3'-cyclic phosphate + H2O
nucleoside 2'-phosphate
show the reaction diagram
Rattus norvegicus Wistar
-
-
-
-
?
cyclic 2',3'-AMP + H2O
2'-AMP
show the reaction diagram
P06961
natural substrate, the 2',3'-cyclic phosphodiesterase activity of the C-terminal HD domain of tRNA nucleotidyltransferase, EC 2.7.7.25, is involved in the repair of the 3-CCA end of tRNA
-
?
additional information
?
-
-
early stages of myelin formation
-
-
-
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 and nuclear factor-1 in the regulation of CNP1 expression
-
?
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 is involved in mediating process formation in oligodendrocytes
-
-
-
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+
-
slight stimulation
Ca2+
-
Ca2+-stimulated and permeability transition pore-associated enzyme phosphorylation
Co2+
-
activation of activity against bis-p-nitrophenyl phosphate
Mg2+
-
slight stimulation
Mg2+
P06961
activataes with 2'-AMP, KD: 0.24 +/- 0.1 mM; activates with 2',3'-cAMP, KD: 0.49 +/- 0.1 mM; activates with ATP, KD ~ 0.1 mM
Mg2+
-
assay buffer
Mg2+
-
activates
Mn2+
-
slight stimulation
Mn2+
-
slight stimulation
Mn2+
-
slight stimulation
Ni2+
P06961
activates with p-nitrophenyl phosphate, KD: 6.0 +/- 0.7 uM; activates with PPi, KD: 1.06 +/- 0.1 uM; hydrolysis of bis-p-nitrophenyl phosphate is strongly dependent on Ni2+
sulfate
-
two sulfate molecules are located in the vicinity of the catalytic site, the active-site sulfate mimics the substrate phosphate group and interacts with all 4 conserved residues of the two HxTx motifs and the two central water molecules in the catalytic site through H-bonds, being also in contact with the backbone carbonyl of Pro320 and bulk solvent. The second sulfate stabilizes the long alpha6-beta5 loop
Mn2+
-
activates
additional information
-
-
additional information
-
-
additional information
-
no divalent metals required
additional information
-
-
additional information
-
no divalent metals required
additional information
P06961
metal-independent 2',3'-cyclic phosphodiesterase activity
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2'-AMP
-
-
2'-AMP
-
product inhibitor
3',5'-cAMP
-
-
5'-AMP
P06961
-
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
adenosine
-
-
arsenate
-
-
arsenite
-
-
Atractyloside
-
noncompetitive
basic fibroblast growth factor
-
-
-
Ca2+
-
74% inhibition at 0.5 mM
Co2+
-
-
Co2+
P06961
-
Cu2+
-
95% inhibition at 0.5 mM
Cu2+
-
75% inhibition at 2 mM
Cu2+
-
-
Cu2+
-
93% inhibition at 0.5 mM
Cu2+
P06961
-
Diethylpyrocarbonate
-
pH 6.5, 22C, time-dependent inhibition, kinetics, completely reversed by 0.5 M hydroxylamine
diisopropyl fluoroacetate
-
-
EDTA
-
-
Elastase
-
little inactivation
-
Fe2+
-
-
Fe2+
-
33% inhibition at 0.5 mM
Fe3+
-
66% inhibition at 0.5 mM
Guanidinium chloride
-
-
heparin
-
-
heparin
-
-
iodoacetamide
-
-
KCN
-
62% inhibition of the catalytic fragment of CNP1
lead
-
90 days exposure of young adult rats to lead in drinking water, decrease both in enzyme protein content and activity
methyl mercury
-
-
methyl methanethiosulfonate
-
42% inhibition of the catalytic fragment of CNP1
NaCH3COO
-
-
NaCl
-
31% inhibition at 0.4 mM
p-chloromercuribenzoate
-
98% inhibition at 0.2 mM
physostygmine
-
-
Polynucleotides
-
polyA, polyU
Sulfhydryl reagent
-
-
-
theophylline
-
-
tRNA
P06961
10 nM, strong competitive inhibition of 2',3'-cyclic phosphodiesterase activity, inhibition is abolished by addition of Mg2+, Mn2+ or Ca2+, but not of Ni2+
Trypsin
-
inactivation
-
Trypsin
-
-
-
Trypsin
-
-
-
tubercidin
-
-
Zn(CH3COO)2
-
-
Zn2+
-
-
Zn2+
-
82% inhibition at 0.5 mM
Zn2+
-
14% inhibition at 2 mM
Zn2+
-
-
Zn2+
-
87% inhibition at 0.5 mM
Zn2+
P06961
-
additional information
-
-
-
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
-
not inhibited by dithiothreitol
-
additional information
P06961
not inhibited by Mg2+, Mn2+, Ca2+ or Ni2+
-
additional information
-
actinomycin D or cycloheximide completely inhibits the dibutyryl-cAMP-induced accumulation of CNP1 mRNA
-
additional information
-
no effect on enzyme activity by calmodulin binding
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Bovine serum albumin
-
-
-
Bovine serum albumin
-
-
-
cytosine arabinoside
-
-
Digitonin
-
-
EDTA
-
-
Hexadecyltrimethylammonium bromide
-
-
histone F3
-
reverses inhibition by polynucleotides
-
lipopolysaccharide
-
enzyme expression is significantly up-regulated in microglial activation induced in vitro by lipopolysaccharide
myelin basic protein
-
reverses inhibition by polynucleotides
-
Na-deoxycholate
-
haemolysed precipitate
Na-deoxycholate
-
-
Na-deoxycholate
-
-
protein activator
-
-
-
Triton X-100
-
-
Triton X-100
-
-
Triton X-100
-
-
Triton X-100
-
-
Triton X-100
-
-
Lubrol WX
-
-
-
additional information
-
solublization of the enzyme by elastase or trypsin
-
additional information
-
-
-
additional information
-
-
-
additional information
-
up-regulation of CNP1 expression by cAMP or its analogues, e.g. dibutyryl-cAMP, in C6 cells transfected with mouse CNP1 gene
-
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
10
1,N6-Etheno-2-azaadenosine-2',3'-cyclic monophosphate
-
-
8.3
1,N6-Ethenoadenosine-2',3'-cyclic monophosphate
-
rat brain
0.25
2',3'-cAMP
-
-
0.32
2',3'-cAMP
-
H7-zRICH-WT mutant
0.37
2',3'-cAMP
-
-
0.38
2',3'-cAMP
-
pig cerebral white matter
0.39
2',3'-cAMP
-
H7-zRICH-C339A mutant
0.49
2',3'-cAMP
P06961
+/- 0.04
0.537
2',3'-cAMP
-
full-length protein
1.64
2',3'-cAMP
-
pH 6.2, 37C
1.9
2',3'-cAMP
-
bovine brain
2.15
2',3'-cAMP
-
pH 6.2, 37, treatment with lead
2.5
2',3'-cAMP
-
H7-zRICH-R332A mutant
6
2',3'-cAMP
-
rat brain
13.1
2',3'-cAMP
-
-
0.8
2',3'-cCMP
-
bovine brain
5.6
2',3'-cCMP
-
bovine brain, elastase fragment
25.2
2',3'-cCMP
-
-
0.57
2',3'-cGMP
-
bovine brain
1.6
2',3'-cGMP
P06961
+/- 0.22
9.2
2',3'-cGMP
-
-
0.098
2',3'-cNADP
-
pH 6, 25C, H309L mutant CNP1
0.1
2',3'-cNADP
-
pH 6, 25C, H309F mutant CNP1
0.104
2',3'-cNADP
-
pH 6, 25C, H230L mutant CNP1
0.119
2',3'-cNADP
-
pH 6, 25C, H230F mutant CNP1
0.23
2',3'-cNADP
-
bovine spinal cord
0.231
2',3'-cNADP
-
pH 6, 25C, C231A mutant CNP1
0.237
2',3'-cNADP
-
pH 6, 25C, recombinant full-length CNP1
0.241
2',3'-cNADP
-
pH 6, 25C, C314S mutant CNP1
0.295
2',3'-cNADP
-
pH 6, 25C, catalytic fragment of CNP1 corresponding to the C-terminal 250 amino acids
0.333
2',3'-cNADP
-
pH 6, 25C, C314A mutant CNP1
0.354
2',3'-cNADP
-
pH 6, 25C, C236A mutant CNP1
0.379
2',3'-cNADP
-
pH 6, 25C, C236S mutant CNP1
0.47
2',3'-cNADP
-
rat brain
0.473
2',3'-cNADP
-
pH 6, 25C, C231S mutant CNP1
0.51
2',3'-cNADP
-
rat liver
0.55
2',3'-cNADP
-
-
8.3
2',3'-cUMP
-
bovine brain
25.3
2',3'-cUMP
-
-
0.553
2',3'-Cyclic AMP
-
wild-type enzyme, pH and temperature not specified in the publication
1.045
2',3'-Cyclic AMP
-
mutant V321A, pH and temperature not specified in the publication
1.055
2',3'-Cyclic AMP
-
mutant H230Q, pH and temperature not specified in the publication
1.192
2',3'-Cyclic AMP
-
mutant H309S, pH and temperature not specified in the publication
1.305
2',3'-Cyclic AMP
-
mutant H230S, pH and temperature not specified in the publication
0.76
2'-AMP
P06961
+/- 0.13
0.046
3'-AMP
-
-
0.19
ADP
P06961
+/- 0.02
0.18
ATP
P06961
+/- 0.01
0.16
bis-p-nitrophenyl phosphate
-
-
0.53
CDP
P06961
+/- 0.09
0.13
CTP
P06961
+/- 0.01
0.49
cyclic 2',3'-AMP
P06961
pH 7, 37C
3.9
cyclic 2',3'-AMP
-
mutant H376D, pH 7.5, 45C
4.7
cyclic 2',3'-AMP
-
mutant H376N, pH 7.5, 45C
6.6
cyclic 2',3'-AMP
-
mutant D236N, pH 7.5, 45C
7.8
cyclic 2',3'-AMP
-
mutant D236A, pH 7.5, 45C
18
cyclic 2',3'-AMP
-
mutant D236E, pH 7.5, 45C; mutant D392E, pH 7.5, 45C; wild-type, pH 7.5, 45C
20
cyclic 2',3'-AMP
-
mutant H189D, pH 7.5, 45C
24
cyclic 2',3'-AMP
-
mutant H323Q, pH 7.5, 45C
28
cyclic 2',3'-AMP
-
mutant H189E, pH 7.5, 45C
29
cyclic 2',3'-AMP
-
mutant H189A, pH 7.5, 45C
31
cyclic 2',3'-AMP
-
mutant D392N, pH 7.5, 45C
32
cyclic 2',3'-AMP
-
mutant H323A, pH 7.5, 45C
60
cyclic 2',3'-AMP
-
mutant R237Q, pH 7.5, 45C
62
cyclic 2',3'-AMP
-
mutant D233E, pH 7.5, 45C
77
cyclic 2',3'-AMP
-
mutant R237A, pH 7.5, 45C
100
cyclic 2',3'-AMP
-
mutant D392A, pH 7.5, 45C; mutant R237K, pH 7.5, 45C
1.6
cyclic 2',3'-GMP
P06961
pH 7, 37C
0.15
NADP
P06961
+/- 0.02
6.2
p-nitrophenyl phosphate
P06961
+/- 0.46
0.1
diphosphate
P06961
+/- 0.004
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
in the prescence of serum albumin or hexadecyltrimethylammonium bromide
-
additional information
additional information
-
-
-
additional information
additional information
-
three enzyme forms
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
7.63
2',3'-cAMP
P06961
+/- 0.48
118
2',3'-cAMP
-
full-length protein
1.97
2',3'-cGMP
P06961
+/- 0.08
1.15
2',3'-cNADP
-
pH 6, 25C, H230F mutant CNP1
1.16
2',3'-cNADP
-
pH 6, 25C, H230L mutant CNP1
1.27
2',3'-cNADP
-
pH 6, 25C, H309L mutant CNP1
1.35
2',3'-cNADP
-
pH 6, 25C, H309F mutant CNP1
6.08
2',3'-cNADP
-
pH 6, 25C, H230L mutant CNP1; pH 6, 25C, H309L mutant CNP1
594
2',3'-cNADP
-
pH 6, 25C, C314S mutant CNP1
825
2',3'-cNADP
-
pH 6, 25C, C231S mutant CNP1
968
2',3'-cNADP
-
pH 6, 25C, C231A mutant CNP1
1107
2',3'-cNADP
-
pH 6, 25C, C236S mutant CNP1
1110
2',3'-cNADP
-
pH 6, 25C, C236S mutant CNP1
1116
2',3'-cNADP
-
pH 6, 25C, C314A mutant CNP1
1120
2',3'-cNADP
-
pH 6, 25C, C314A mutant CNP1
1130
2',3'-cNADP
-
pH 6, 25C, C397S mutant CNP1
1132
2',3'-cNADP
-
pH 6, 25C, C397S mutant CNP1
1195
2',3'-cNADP
-
pH 6, 25C, recombinant full-length wild-type CNP1
1200
2',3'-cNADP
-
pH 6, 25C, recombinant full-length wild-type CNP1
1476
2',3'-cNADP
-
pH 6, 25C, C236A mutant CNP1
1480
2',3'-cNADP
-
pH 6, 25C, C236A mutant CNP1
1690
2',3'-cNADP
-
pH 6, 25C, catalytic fragment of CNP1 corresponding to the C-terminal 250 amino acids
14
2',3'-Cyclic AMP
-
mutant H230S, pH and temperature not specified in the publication
21
2',3'-Cyclic AMP
-
mutant H309S, pH and temperature not specified in the publication
24
2',3'-Cyclic AMP
-
mutant H230Q, pH and temperature not specified in the publication
732
2',3'-Cyclic AMP
-
mutant V321A, pH and temperature not specified in the publication
940
2',3'-Cyclic AMP
-
wild-type enzyme, pH and temperature not specified in the publication
3.09
2'-AMP
P06961
+/- 0.14
1.24
ADP
P06961
+/- 0.07
3.78
ATP
P06961
+/- 0.12
4.83
CDP
P06961
+/- 0.39
3.36
CTP
P06961
+/- 0.17
0.031 - 0.51
cyclic 2',3'-AMP
P06961
pH 7, 37C
1.45
cyclic 2',3'-AMP
-
mutant H189A, pH 7.5, 45C
1.8
cyclic 2',3'-AMP
-
mutant D392A, pH 7.5, 45C
3.2
cyclic 2',3'-AMP
-
mutant H376D, pH 7.5, 45C
3.25
cyclic 2',3'-AMP
-
mutant D233E, pH 7.5, 45C
4.5
cyclic 2',3'-AMP
-
mutant D236A, pH 7.5, 45C
5.1
cyclic 2',3'-AMP
-
mutant H376N, pH 7.5, 45C
5.8
cyclic 2',3'-AMP
-
mutant D236N, pH 7.5, 45C
6
cyclic 2',3'-AMP
-
mutant D236E, pH 7.5, 45C
6.5
cyclic 2',3'-AMP
-
mutant H323Q, pH 7.5, 45C
7.63
cyclic 2',3'-AMP
P06961
pH 7, 37C
8.6
cyclic 2',3'-AMP
-
mutant R237A, pH 7.5, 45C
8.9
cyclic 2',3'-AMP
-
wild-type, pH 7.5, 45C
9.1
cyclic 2',3'-AMP
-
mutant H323A, pH 7.5, 45C
15.9
cyclic 2',3'-AMP
-
mutant D392E, pH 7.5, 45C
17.2
cyclic 2',3'-AMP
-
mutant H189E, pH 7.5, 45C
18.7
cyclic 2',3'-AMP
-
mutant D392N, pH 7.5, 45C
20.2
cyclic 2',3'-AMP
-
mutant R237Q, pH 7.5, 45C
26.2
cyclic 2',3'-AMP
-
mutant R237K, pH 7.5, 45C
34.3
cyclic 2',3'-AMP
-
mutant H189D, pH 7.5, 45C
1.97
cyclic 2',3'-GMP
P06961
pH 7, 37C
2.94
cyclic 2',3'-GMP
P06961
pH 7, 37C
14.9
NADP
P06961
+/- 0.5
10.3
p-nitrophenyl phosphate
P06961
+/- 0.28
2.51
diphosphate
P06961
+/- 0.05
additional information
additional information
-
-
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
220
2',3'-cAMP
-
full-length protein
942
10
2',3'-Cyclic AMP
-
mutant H230S, pH and temperature not specified in the publication
19884
20
2',3'-Cyclic AMP
-
mutant H230Q, pH and temperature not specified in the publication; mutant H309S, pH and temperature not specified in the publication
19884
700
2',3'-Cyclic AMP
-
mutant V321A, pH and temperature not specified in the publication
19884
1700
2',3'-Cyclic AMP
-
wild-type enzyme, pH and temperature not specified in the publication
19884
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.5
2'-AMP
-
-
0.59
5'-AMP
P06961
-
0.00000168
tRNA
P06961
hydrolysis of cyclic 2',3'-AMP
0.29
tRNA
P06961
with ATP
1.08
tRNA
P06961
with 2'-AMP
1.68
tRNA
P06961
with 2',3'-cAMP
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.066
-
rabbit, adrenal gland
0.133
-
2',3'-cAMP, hole mitochondria
0.24
-
mitochondrial inner membrane
0.28
-
mitochondrial outer membrane
1.49
P06961
+/- 0.08, ADP
2.36
P06961
+/- 0.10, 2',3'-cGMP
3.01
P06961
+/- 0.06, diphosphate
3.21
P06961
+/- 0.1, 2',3'-cAMP
3.71
P06961
+/- 0.17, 2'-CMP
4.03
P06961
+/- 0.20, CTP
4.53
P06961
+/- 0.14, ATP
5.8
P06961
+/- 0.47, CDP
6.28
-
2',3 '-cCMP, fish retina
11.2
-
pH 6.2, 37, treatment with lead
12.4
P06961
+/- 0.34, p-nitrophenyl phosphate
13.4
-
pH 6.2, 37C
17.9
P06961
+/- 0.6, NADP
35
-
2',3'-cAMP, frog brain
130.6
-
ZRICH-WT-enzyme
280
-
2',3'-cGMP
600
-
2',3'-cUMP
2090
-
2',3'-cAMP
2140
-
2',3'-cCMP
2300
-
-
2680
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
mitochondrial inner and outer membrane, effect of chronic ethanol ingestion
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5
-
activity against bis-p-nitrophenyl phosphate
5.4 - 6.2
-
without detergent
6 - 7
-
-
6
-
in the prescence of serum albumin or hexadecyltrimethylammonium bromide
6
-
assay at
6.1 - 6.7
-
-
6.6
-
-
8 - 8.3
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4 - 6.5
-
-
4 - 8.5
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
-
assay at
37
P06961
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30 - 37
-
30C: optimum, 37C: 90% of optimum activity
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5 - 9.3
-
isoelectric focusing
9
-
2D electrophoresis and immunoblotting, lipid raft fraction from a young monkey
9.2
-
theoretical value
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
Rattus norvegicus Sprague-Dawley, Rattus norvegicus Wistar
-
-
-
Manually annotated by BRENDA team
-
white matter
Manually annotated by BRENDA team
-
two enzyme isoforms in chicken, just one isoform in bullfrog
Manually annotated by BRENDA team
-
CNP is associated with tubulin from brain
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
subventricular zone rostral extension, CNPase expression pattern during development from postnatal day 3 to 60
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
embryonic brain
Manually annotated by BRENDA team
-
developing brain
Manually annotated by BRENDA team
-
amoeboid microglial cells in the postnatal rat brain
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
amoeboid microglial cells in the postnatal rat brain
-
Manually annotated by BRENDA team
Rattus norvegicus Wistar
-
amoeboid microglial cells in the postnatal rat brain
-
Manually annotated by BRENDA team
-
presence of enzyme immunoreactive material at birth, progressive reduction with age with complete loss at postnatal day 18
Manually annotated by BRENDA team
-
cerebellar, both isoforms CNP1 and CNP2
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
with age, CNP accumulates throughout brain white matter accompanied by proteolytic fragments of CNP. Equal increase in both isoforms CNP1 and CNP2
Manually annotated by BRENDA team
-
presence of enzyme immunoreactive material at birth, progressive reduction with age with complete loss at postnatal day 18
Manually annotated by BRENDA team
-
ubiquitinated CNP
Manually annotated by BRENDA team
-
DRG explant cultures
Manually annotated by BRENDA team
-
ATCC CRL 8305, thyroid cells, CNP is firmly associated with FRTL-5 cells
Manually annotated by BRENDA team
-
olfactory bulb ensheathing glia in explant cultures
Manually annotated by BRENDA team
-
from newborn rat brain
Manually annotated by BRENDA team
-
neonatal mouse brain cells
Manually annotated by BRENDA team
-
oligodendrocyte-enriched cultures of neonatal rat brain glial cells, CNP2
Manually annotated by BRENDA team
P09543
quantitative isozymes expression analysis in hepatoma cell lines
Manually annotated by BRENDA team
P09543
the enzyme is expressed in liver tissues with hepatitis B virus infection
Manually annotated by BRENDA team
Rattus norvegicus Wistar
-
-
-
Manually annotated by BRENDA team
-
abundantly in the cytoplasmic compartments of CNS myelin
Manually annotated by BRENDA team
-
myelinating cell
Manually annotated by BRENDA team
-
with age, CNP accumulates in myelin accompanied by proteolytic fragments of CNP. Equal increase in both isoforms CNP1 and CNP2
Manually annotated by BRENDA team
Rattus norvegicus Wistar
-
-
-
Manually annotated by BRENDA team
-
a highly abundant membrane-associated enzyme in the myelin sheath of the vertebrate nervous system
Manually annotated by BRENDA team
-
the enzyme is a quantitatively major enzyme in myelin, where it localizes to the non-compact regions and is bound to the membrane surface
Manually annotated by BRENDA team
-
the enzyme is most abundant protein in non-compact myelin and the third-most abundant protein overall in CNS myellin
Manually annotated by BRENDA team
-
the enzyme is one of the most abundant proteins in CNS myelin
Manually annotated by BRENDA team
-
peripheral nerve sheath tumors, immunohistochemic and histochemic analysis of 63 tumors from 44 cattle: 35 schwannomas, 9 neurofibromas, 14 hybrid (neurofibroma-schwannoma) tumors, and 5 malignant peripheral nerve sheath tumors
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
olfactory bulb ensheathing glia in explant cultures
Manually annotated by BRENDA team
-
olfactory ensheathing cells, the nonmyelinating glial cells of the olfactory nerves and bulb, in situ immunohistochemic analysis, overview
Manually annotated by BRENDA team
-
bipotential proliferating and differentiating CG-4 cells
Manually annotated by BRENDA team
-
cerebellar, both isoforms CNP1 and CNP2
Manually annotated by BRENDA team
-
the two isoforms CNP1 and CNP2 are differentially regulated during the process of maturation, CNP expression pattern
Manually annotated by BRENDA team
Rattus norvegicus Wistar
-
-
-
Manually annotated by BRENDA team
-
peripheral nerve sheath tumors, immunohistochemic and histochemic analysis of 63 tumors from 44 cattle: 35 schwannomas, 9 neurofibromas, 14 hybrid (neurofibroma-schwannoma) tumors, and 5 malignant peripheral nerve sheath tumors
Manually annotated by BRENDA team
-
optic nerve regenerating retinas
Manually annotated by BRENDA team
-
myelinating, colocalization of CNPase and CaM during Schwann cell myelination in culture
Manually annotated by BRENDA team
-
presence of enzyme immunoreactive material at birth, progressive reduction with age with complete loss at postnatal day 18
Manually annotated by BRENDA team
-
myelin sheaths of the cerebral white matter
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley, Rattus norvegicus Wistar
-
-
-
Manually annotated by BRENDA team
additional information
-
CNP2 is barely detectable in testis and thymus
Manually annotated by BRENDA team
additional information
-
MO3.13 cell, ubiquitinated CNP
Manually annotated by BRENDA team
additional information
-
bovine peripheral nerve sheath tumors commonly have both schwannomatous and neurofibromatous areas
Manually annotated by BRENDA team
additional information
-
spatiotemporal distribution of CNPase, an early oligodendrocyte/Schwann cell marker, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
abundantly in the cytoplasmic compartments of CNS myelin
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
P09543
isozyme CNP1
Manually annotated by BRENDA team
-
integral membrane protein, inner and outer mitochondrial membrane
Manually annotated by BRENDA team
-
exclusively associated with the cytosolic side of the membrane
Manually annotated by BRENDA team
-
single and double-unit membrane, from non-compact regions of myelin
Manually annotated by BRENDA team
-
myelin membranes
Manually annotated by BRENDA team
-
myelin membranes
Manually annotated by BRENDA team
-
cytosolic side of the membrane
Manually annotated by BRENDA team
-
cytosolic side of the membrane
Manually annotated by BRENDA team
-
membrane-bound, microtubule-associated protein, membrane anchor for tubulin
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
membrane-anchored enzyme present on the cytosolic side of non-compact myelin
Manually annotated by BRENDA team
Rattus norvegicus Wistar
-
-
-
Manually annotated by BRENDA team
-
tubulin from brain, microtubule-associated protein, membrane anchor for tubulin, membrane-bound
Manually annotated by BRENDA team
-
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.
Manually annotated by BRENDA team
-
distribution of isozymes in mitochondrial fractions, i.e. myelin fraction, synaptic and nonsynaptic mitochondria, obtained after separation of brain mitochondria
Manually annotated by BRENDA team
-
isoform II, intermembrane space
Manually annotated by BRENDA team
P09543
the N-terminus ofisozyme CNP2 serves as a mitochondrial targeting signal and translocates it to the mitochondrion
Manually annotated by BRENDA team
-
of marrow stromal cell
Manually annotated by BRENDA team
Rattus norvegicus Wistar
-
distribution of isozymes in mitochondrial fractions, i.e. myelin fraction, synaptic and nonsynaptic mitochondria, obtained after separation of brain mitochondria
-
Manually annotated by BRENDA team
additional information
-
-
-
Manually annotated by BRENDA team
additional information
-
subcellular distribution of CNP
-
Manually annotated by BRENDA team
additional information
-
partially localize within lipid rafts
-
Manually annotated by BRENDA team
additional information
-
ubiquitinated CNP in the Triton X-100 insoluble lipid raft associated fractions of myelin
-
Manually annotated by BRENDA team
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
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
10000
-
sedimentation analysis in presence of bovine serum albumin, bovine brain
135388
23000
-
gel filtration
135387
31000
-
gel filtration
135242
31000
-
gel filtration
135390
36500
-
sedimentation coefficient
135242
40000
-
2D electrophoresis and immunoblotting, lipid raft fraction from a young monkey
708596
41200 - 43900
-
MALDI TOF mass spectrometry
694176
44000
-
monomeric enzyme, light scattering and refractive index
730687
44850
-
sequence analysis, bovine brain
135384
45100
-
sequence analysis, human brain
135386
46000
-
-
135418
46000
-
endogenous CNP, immunoblot analysis
708596
47000
-
endogenous CNP, SDS-PAGE
713118
47580
-
theoretical value
694176
48000
-
endogenous CNP, immunoblot analysis
708596
49000 - 51000
-
antibody column
135418
50000
-
sucrose density gradient centrifugation without bovine serum albumin
135388
50000
-
GC-CNP transfected MO3.13 cells, immunoblot analysis
708596
50000
-
2D electrophoresis and immunoblotting, lipid raft fraction from a young monkey
708596
55000
-
gel filtration
135415
60000
-
GC-CNP transfected MO3.13 cells, immunoblot analysis
708596
78000
-
dimeric enzyme, light scattering and refractive index
730687
100000
-
gel filtration and gel electrophoresis under non reducing conditions, sucrose density gradient centrifugation
135381
100000
-
sucrose density gradient centrifugation in the presence of bovine serum albumin or human gamma globulin or carbonic anhydrase or myelin basic protein
135388
120000
-
gel filtration, native conditions, bovine brain
135388
128000
-
gel electrophoresis, second major band, microsomes
135412
150000
-
GC-CNP/YN-Ub complex transfected MO3.13 cells, immunoblot analysis
708596
250000
-
GC-CNP/YN-Ub complex transfected MO3.13 cells, immunoblot analysis
708596
263000
-
gel electrophoresis, first major band, microsomes
135412
additional information
-
in lipid raft fraction from an aged monkey, evidence of sequential CNP proteolysis, abundance of CNP immunoreactive higher molecular weight material
708596
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 46000, SDS-PAGE
?
-
x * 74000, SDS-PAGE
?
-
x * 51000, SDS-PAGE
?
-
x * 24000, SDS-PAGE
?
-
x * 33000, SDS-PAGE
?
-
27000-31000, SDS-PAGE
?
-
x * 110000 SDS-PAGE
?
-
x * 44000-47000, SDS-PAGE
?
-
x * 46000, CNP1, x * 48000, CNP2
?
-
x * 46000, CNP1, x * 48000, CNP2, SDS-PAGE
?
-
x * 46000, major CNP isoenzyme, x * 48000, minor CNP isoenzyme
?
-
x * 26700, SDS-PAGE, C-terminal domain. x * 45200, SDS-PAGE, full-length CNPase
?
-
x * 46000, phosphorylated mitochondrial enzyme, SDS-PAGE
?
Rattus norvegicus Wistar
-
x * 46000, SDS-PAGE
-
dimer
P06961
-
dimer
-
1* 44000 + 1* 54000, SDS-PAGE
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
dimer
-
1 * 44600 + 1* 45900, SDS-PAGE
dimer
-
1* 54000 + 1* 51000, SDS-PAGE
monomer
-
1 * 30000, SDS-PAGE
monomer
P06961
predominantly
oligomer
P06961
-
oligomer
-
50000-100000, SDS-PAGE
monomer or dimer
-
monomer-dimer equilibrium for full-length enzyme, dimerization is possibly mediated by the N-terminal domain
additional information
-
enzyme interacts with tubulin, binding preferentially to tubulin heterodimers and inducing assembly of mircotubulues by cooperation with tubulin
additional information
-
the two domains of the enzyme form an elongated molecule, three-dimensional model of full-length enzyme, overveiw
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
-
CNPase isoform II is responsible for mitochondrial import, which is regulated via phosphorylation by protein kinase C
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
-
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
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
-
CNP is isoprenylated and palmitoylated
side-chain modification
-
isoprenylated at Cys-397
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
catalytic fragment of enzyme
-
phosphodiesterase domain of the enzyme with bound citrate, sulfate, NADP+, and 2-AMP, mixing of protein in 10 mM sodium citrate pH 5.5, 50 mM NaCl, 10% glycerol, and 1 mM DTT, with crystallization solution, X-ray diffraction structure determination and analysis at 1.74-2.4 A resolution, molecular replacement and modeling. Crystallization is only successful with sulfate or citrate present
-
structure analysis
-
wild-type and mutant enzymes complexed with substrate 2',3'-cyclic AMP, product 2'-AMP, and phosphorothioate analogues, and H230S mutant complexed with the substrate 2',3'-cNADP+, X-ray diffraction structure determination and analysis at 1.9-2.3 A resolution
-
modeling of enzyme N-terminal region and simulation of docking of nucleotides
-
structure analysis
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5
-
in pH 5.5 and in the presence of 500 mM NaCl, CNPase is much more stable than at neutral pH with lower salt content
707896
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
40
-
50% loss of activity after 5 min
135415
50 - 70
-
inactivation
135405
50
-
completely inactivated after 5 min
135415
55
-
no loss of activity after 10 min
135387
60
-
85% loss of activity after 15 min
135401
65 - 75
-
increase in the melting temperature induced by both pH 5.5 and high salt concentration. At pH 5.5, without NaCl: ca. 68C and with 500 mM NaCl: ca. 75C. At pH 7.5 without NaCl and with 500 mM NaCl: ca. 70C
707896
65
-
20% loss of activity after 10 min
135387
80
-
82.2% loss of activity after 10 min
135387
100
-
80% loss of activity, and completely eliminated after 20 min, Co2+ protects against heat inactivation
135405
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
freezing and thawing, not affected by several cycles
-
dilution, inactivates
-
freezing and thawing, inactivates
-
serum albumin, 2'-AMP and NaCl, stabilizes
-
stable
P06961
25 mM citric acid, 50 mM Na2HPO4 buffer, pH 6.2
-
bovine serum albumin, stable for 6 months
-
freezing and thawing, not affected by several cycles
-
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
-30C, stable for several months
-
4C, stable for 2 days
-
0-4C, 5 mM Tris-HCl buffer, pH 7.6, stable for 2 months
-
4C, 6 months, more than 90% of activity retained
-
4C, 5% glycerol, 0.5 M NaCl, pH 7.5, no loss in activity after several months
P06961
4C, for weeks
-
-20C for at least 1 month or at 4C for 3 weeks
-
-80C for 24 h, 90% loss of activity
-
-70C, stable for at least 5 months
-
4C, Tris-acetate buffer, 0.5 mM dithiothreitol, pH 7.6, 10% glycerol, protease inhibitor mix, 3 days
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
1990fold
-
partial, by delipidation, solubilization, gel chromatography, resolubilization, ion-exchange chromatography and affinity chromatography
-
recombinant tRNA nucleotidyltransferase, EC 2.7.7.25, with its HD domain possessing 2',3'-cyclic phosphodiesterase activity
P06961
by Ni-affinity chromatography followed by gel filtration
-
immunopurification, to homogeneity
-
recombinant CNP1 and C-terminal deletion mutant
-
recombinant His-tagged wild-type full-length enzyme and truncated mutants by nickel affinity chromatography and gel filtration or by calmodulin affinity chromatography
-
recombinant wild-type and mutant CNP1
-
partial, 1196.4fold band 1, 739.9fold band 2, microsomes
-
10000fold
-
16000fold to near homogeneity
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
-
bovine brain
-
GC-CNP encoding 155238 aa of GFP fused to the N-terminus of CNP co-transfected with YN-Ub into COS-7 cells
-
; tRNA nucleotidyltransferase, EC 2.7.7.25, with its HD domain possessing 2',3'-cyclic phosphodiesterase activity
P06961
expressed in HEK-293 cells
-
GC-CNP encoding 155238 aa of GFP fused to the N-terminus of CNP co-transfected with YN-Ub into MO3.13 cells
-
gene CNP1, two isozymes, which originate from two alternative promoters and 3',5'-cAMP-regulated splicing of one of the mRNA variants produced from the CNP1 gene on chromosome 17
-
human brain, subcloned into a plasmid vector
-
overexpression in Rattus norvegicus preglomerular vascular smooth muscle cells increasing the metabolism of exogenous 2,3'-cAMP to 2'-AMP
-
overexpression in transgenic mice
-
CNP gene with various deletions of the CNP promoter, expression in rat C6 cells, regulation of CNP1 promoter activity by cAMP
-
subcloned into pTH27, expressed in Escherichia coli Rosetta (DE3) with a TEV protease-cleavable His-tag
-
expression in Saccharomyces cerevisiae
-
expression with His-tag
-
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
-
subcloning into the Bluescript vector
-
wild type and mutant CNP proteins are produced in vitro in rabbit reticulocyte lysate in the presence of S-methionine
-
wild-type and mutant CNP1, expression in Escherichia coli BL21
-
wild-type and mutant CNP2, expression in 293T human kidney fibroblast cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
treatment of purified adult canine olfactory ensheathing cells with fibroblast growth factor-2 significantly reduces CNPase expression at the protein and mRNA level
-
expression of CNP is reduced by 10% in schizophrenics compared with controls, but the difference is not significant
-
CNP mRNA levels do not change with age
-
markedly enhanced enzyme expression, CNPase protein and mRNA expression, in microglia after activation by lipopolysaccharide treatment
-
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
-
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
-
markedly enhanced enzyme expression, CNPase protein and mRNA expression, in microglia after activation by lipopolysaccharide treatment
-
markedly enhanced enzyme expression, CNPase protein and mRNA expression, in microglia after activation by lipopolysaccharide treatment
Rattus norvegicus Sprague-Dawley, Rattus norvegicus Wistar
-
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D21A
P06961
tRNA nucleotidyltransferase mutant, EC 2.7.7.25, no effect on the 2',3'-cyclic phosphodiesterase activity
D23A
P06961
tRNA nucleotidyltransferase mutant, EC 2.7.7.25, no effect on the 2',3'-cyclic phosphodiesterase activity
D256A
P06961
HD domain mutant without detectable 2',3'-cyclic phosphodiesterase activity
D306A
P06961
HD domain mutant with 2',3'-cyclic phosphodiesterase activity
H225A
P06961
HD domain mutant without detectable 2',3'-cyclic phosphodiesterase activity
H305A
P06961
HD domain mutant without detectable 2',3'-cyclic phosphodiesterase activity
H230Q
-
site-directed mutagenesis, the mutation of the active site residue highly reduces the enzyme activity compared to the wild-type enzyme
H230Q/H309Q
-
site-directed mutagenesis, the mutation of the active site residue completely abolishes enzyme activity compared to the wild-type enzyme
H230S
-
site-directed mutagenesis, the mutation of the active site residue highly reduces enzyme activity compared to the wild-type enzyme
H309Q
-
site-directed mutagenesis, the mutation of the active site residue highly reduces enzyme activity compared to the wild-type enzyme
V321A
-
site-directed mutagenesis, Val321 stacks against the substrate adenine ring, the mutation does not affect kcat significantly but doubles Km, indicating a functional active site but slightly compromised substrate binding
C231A
-
CNP1 catalytic fragment mutant, kinetics
C231S
-
CNP1 catalytic fragment mutant, kinetics
C236A
-
CNP1 catalytic fragment mutant, kinetics
C236S
-
CNP1 catalytic fragment mutant, kinetics
C314A
-
CNP1 catalytic fragment mutant, kinetics
C314S
-
CNP1 catalytic fragment mutant, kinetics
C397S
-
CNP1 catalytic fragment mutant, kinetics
H230A/T232A/H309A/T311A
-
catalytically inactive
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
S22A
-
CNP2 mutant with reduced phosphate incorporation
S23A
-
CNP2 mutant
S9A
-
CNP2 mutant with reduced phosphate incorporation
S9A/S22A
-
CNP2 double mutant without phosphate incorporation
D233A
-
catalytic activity is neligible
D233E
-
decrease in catalytic efficiency by factor 9
D233N
-
catalytic activity is neligible
D236A
-
increase in enzyme affinity for substrate
D236E
-
kinetics similar to wild-type
D236N
-
increase in enzyme affinity for substrate
D392A
-
decrease of both kcat and Km value
D392E
-
2fold increase in kcat value without affecting Km value
D392N
-
2fold increase in kcat value without affecting Km value
H189A
-
slight increase of Km value with 6fold decrease in kcat value
H189D
-
4fold increase in kcat value without affecting Km value
H189E
-
2fold increase in kcat value without affecting Km value
H323A
-
kinetics similar to wild-type
H323Q
-
kinetics similar to wild-type
H376D
-
60% increase in catalytic efficiency
H376N
-
twofold increase in catalytic efficiency
R237A
-
4fold increase in Km value
R237K
-
6fold increase in Km value
R237Q
-
3fold increase in Km value
additional information
-
-
H309S
-
site-directed mutagenesis, the mutation of the active site residue completely abolishes enzyme activity compared to the wild-type enzyme
additional information
-
CNP1 promoter deletion and replacement mutants, effect on the stimulatory effect of cAMP on CNP1 gene expression
additional information
-
enzyme overexpression induces dramatic morphology changes in both glial and nonglial cells, resulting in microtubule and F-actin reorganization and formation of branched processes. Cultured oligodendrocytes from enzyme-deficient mice extend smaller outgrowths with less arborized processes
additional information
-
enzyme knockdown by siRNA knockdown of CNPase in BV-2 cells
M21L
-
CNP2 mutant
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
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
2',3'-cyclic nucleotide 3'-phosphodiesterase is a stable marker for in situ detection of canine but not rat olfactory ensheathing cells
diagnostics
-
2',3'-cyclic nucleotide 3'-phosphodiesterase is a stable marker for in situ detection of canine but not rat olfactory ensheathing cells
medicine
-
no association between genetic variation in the CNP enzyme gene and schizophrenia in the Han Chinese population
medicine
-
2',3'-cyclic nucleotide 3'-phosphodiesterase single nucleotide polymorphism rs2070106 is potentially associated with schizophrenia
medicine
-
CNPase is associated with multiple sclerosis
medicine
-
the rs207016 genotype of CNP is not likely to contribute to the coordinated down-regulation of oligodendrococyte-related genes in schizophrenia
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