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evolution
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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
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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
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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
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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
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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
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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
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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
knockdown of the enzyme expression moderately improves hepatitis B viral production in the HepG2.2.15 cells treated with IFN-alpha
malfunction
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truncations after amino acid 164 in recombinant rat enzyme result in a loss of phosphodiesterase activity
malfunction
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enzyme deletion attenuates ischemia-reperfusion-induced acute kidney injury, in part by accelerating autophagy with targeted removal of damaged mitochondria
metabolism
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role of 2',3'-cyclic nucleotide 3'-phosphodiesterase in the renal 2',3'-cAMP-adenosine pathway, overview
metabolism
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the enzyme is involved in the regulation of the kinases Akt and GSK3beta
physiological function
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an age-related impairment in proteasomal proteolysis and subsequent accumulation of ubiquitinated CNP activates alternative proteolytic mechanisms leading to CNP fragmentation
physiological function
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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
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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
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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
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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
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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
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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
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the enzyme encoding gene may play an important role as a putative anti-inflammatory gene both in normal and injured brain
physiological function
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the enzyme encoding gene may play an important role as a putative anti-inflammatory gene both in normal and injured brain
physiological function
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the enzyme interacts with membrane surfaces, cytoskeletal proteins, and calmodulin
physiological function
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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
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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
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
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
the enzyme interacts with microtubules and promotes tubulin polymerization
physiological function
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the enzyme encoding gene may play an important role as a putative anti-inflammatory gene both in normal and injured brain
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physiological function
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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
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physiological function
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the enzyme encoding gene may play an important role as a putative anti-inflammatory gene both in normal and injured brain
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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
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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
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role for the N-terminal domain of the enzyme in mediating multiple molecular interactions, molecular modeling, overview
additional information
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role for the N-terminal domain of the enzyme in mediating multiple molecular interactions, molecular modeling, overview
additional information
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structure of the 2'-cyclic AM-bound enzyme active site and its catalytic mechanism, overview
additional information
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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
additional information
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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