This enzyme participates in the eukaryotic ubiquitin-dependent Arg/N-end rule pathway of protein degradation, promoting the turnover of intracellular proteins that initiate with Met-Asn. Following the acetylation and removal of the initiator methionine, the exposed N-terminal asparagine is deaminated, resulting in its conversion to L-aspartate. The latter serves as a substrate for EC 2.3.2.8, arginyltransferase, making the protein susceptible to arginylation, polyubiquitination and degradation as specified by the N-end rule.
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SYSTEMATIC NAME
IUBMB Comments
protein N-terminal asparagine amidohydrolase
This enzyme participates in the eukaryotic ubiquitin-dependent Arg/N-end rule pathway of protein degradation, promoting the turnover of intracellular proteins that initiate with Met-Asn. Following the acetylation and removal of the initiator methionine, the exposed N-terminal asparagine is deaminated, resulting in its conversion to L-aspartate. The latter serves as a substrate for EC 2.3.2.8, arginyltransferase, making the protein susceptible to arginylation, polyubiquitination and degradation as specified by the N-end rule.
hNTAN1 is highly selective for the hydrolysis of N-terminal peptidyl L-Asn but fails to deamidate free L-Asn or L-Gln, N-terminal peptidyl L-Gln, or acetylated N-terminal peptidyl L-Asn
hNTAN1 is highly selective for the hydrolysis of N-terminal peptidyl L-Asn but fails to deamidate free L-Asn or L-Gln, N-terminal peptidyl L-Gln, or acetylated N-terminal peptidyl L-Asn
dual specificity of yeast Nta1 (yNta1), importance of second-position residues in Asn/Gln-bearing N-terminal degradation signals (N-degrons), also cf. EC 3.5.1.121 Specific hydrogen bonds stabilize interactions between N-degron peptides and hydrophobic peripheral regions of the active site pocket, interactions between Nta1 and N-degron peptides, detailed overview. The enzyme shows asparagine-specific enzyme activity with dipeptides An-Val and Asn-Gly, Michaelis-Menten kinetics
dual specificity of yeast Nta1 (yNta1), importance of second-position residues in Asn/Gln-bearing N-terminal degradation signals (N-degrons), also cf. EC 3.5.1.121 Specific hydrogen bonds stabilize interactions between N-degron peptides and hydrophobic peripheral regions of the active site pocket, interactions between Nta1 and N-degron peptides, detailed overview. The enzyme shows asparagine-specific enzyme activity with dipeptides An-Val and Asn-Gly, Michaelis-Menten kinetics
enzyme PNAD does not act on internal asparagine residues and requires a free Nalpha-amino groups. It has reduced or no activity on NH2-terminal asparagine dipeptides and no activity toward free asparagine or asparagine amide. It does not act on any NH2-terminal glutamine substrates
hNTAN1 is shown to possess a critical Cys residue that is absolutely required for catalysis, corroborated in part by abolishment of activity through the Cys75Ala point mutation
Ntan1-/- mice lack NtN-amidase and the asparagine-specific branch of the N-end rule pathway. The phenoytpe shows altered activity, social behavior, and spatial memory in mice lacking the NTAN1p amidase and the asparagine branch of the N-end rule pathway. The Ntan1-/- mouse strains lacking the NtN-amidase activity but retaining glutamine-specific NtQ amidase, EC 3.5.1.122, show that the two enzymes are encoded by different genes. Among the normally short-lived N-end rule substrates, only those bearing N-terminal asparagine became long-lived in Ntan1-/- fibroblasts. The Ntan1-/- mice are fertile and outwardly normal but differ from their congenic wild-type counterparts in spontaneous activity, spatial memory, and a socially conditioned exploratory phenotype
NTAN1-deficient mice are better than wild-type mice on black-white and horizontal-vertical discrimination learning. They are also better at 8-week Morris maze retention testing when a reversal trial is not included in the testing procedures. In all three tasks NTAN1-deficient mice appear to use a strong win-stay strategy. It is concluded that inactivating the asparagine-specific branch of the N-end rule pathway in mice results in impaired spatial learning with concomitant compensatory restructuring of the nervous system in favor of non-spatial (stimulus-response) learning
recombinant mouse NtN-amidase enzyme expressed in an enzyme-mutant Saccharomyces cerevisiae strain can implement the asparagine-specific subset of the yeast N-end rule
NTAN1-deficient mice are better than wild-type mice on black-white and horizontal-vertical discrimination learning. They are also better at 8-week Morris maze retention testing when a reversal trial is not included in the testing procedures. In all three tasks NTAN1-deficient mice appear to use a strong win-stay strategy. It is concluded that inactivating the asparagine-specific branch of the N-end rule pathway in mice results in impaired spatial learning with concomitant compensatory restructuring of the nervous system in favor of non-spatial (stimulus-response) learning
Ntan1-/- mice lack NtN-amidase and the asparagine-specific branch of the N-end rule pathway. The phenoytpe shows altered activity, social behavior, and spatial memory in mice lacking the NTAN1p amidase and the asparagine branch of the N-end rule pathway. The Ntan1-/- mouse strains lacking the NtN-amidase activity but retaining glutamine-specific NtQ amidase, EC 3.5.1.122, show that the two enzymes are encoded by different genes. Among the normally short-lived N-end rule substrates, only those bearing N-terminal asparagine became long-lived in Ntan1-/- fibroblasts. The Ntan1-/- mice are fertile and outwardly normal but differ from their congenic wild-type counterparts in spontaneous activity, spatial memory, and a socially conditioned exploratory phenotype
the enzyme is involved in the mammalian N-end rule pathway, comparison of enzymatic reactions that underlie the activity of N-dt and N-ds residues in the N-end rule pathways of different organisms, overview
the enzyme is involved in the mammalian N-end rule pathway, comparison of enzymatic reactions that underlie the activity of N-dt and N-ds residues in the N-end rule pathways of different organisms, overview
the enzyme is involved in the mammalian N-end rule pathway. The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. N-terminal asparagine and glutamine are tertiary destabilizing residues, in that they are enzymatically deamidated to yield secondary destabilizing residues aspartate and glutamate, which are conjugated to arginine, a primary destabilizing residue
the first step of the hierarchically organized Arg/N-end rule pathway of protein degradation is deamidation of the N-terminal glutamine and asparagine residues of substrate proteins to glutamate and aspartate, respectively. These reactions are catalyzed by the N-terminal amidase (Nt-amidase) Nta1 in fungi such as Saccharomyces cerevisiae, and by the glutamine-specific Ntaq1 and asparagine-specific Ntan1 Nt-amidases in mammals. Specific deamidation mechanisms in the first step of the N-end rule pathway
the enzyme is involved in the mammalian N-end rule pathway, comparison of enzymatic reactions that underlie the activity of N-dt and N-ds residues in the N-end rule pathways of different organisms, overview
the enzyme is involved in the mammalian N-end rule pathway. The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. N-terminal asparagine and glutamine are tertiary destabilizing residues, in that they are enzymatically deamidated to yield secondary destabilizing residues aspartate and glutamate, which are conjugated to arginine, a primary destabilizing residue
conversion of the resulting NH2-terminal asparagine to aspartic acid by enzyme PNAD renders the protein susceptible to arginylation, polyubiquitinylation and degradation as specified by the N-end rule. Proteins beginning with Met-Asp, Met-Glu, and Met-Asn sequences are Nalpha-acetylated, while those beginning with Met-Gln sequences are not. The enzyme protein NH2-terminal asparagine deamidase (PNAD) catalyzes the specific deamidation of peptide-bound NH2-terminal asparagine residues
Ntan1 (amidohydrolase for N-terminal asparagine) is a magnetism responsive gene in rat brain. Ntan1 is an essential component of a protein degradation signal, which is a destabilizing N-terminal residue of a protein, in the N-end rule. Overexpression of gene Ntan1 results in a marked decrease in the MAP2 protein expression in hippocampal neurons. Brief magnetism leads to the induction of Ntan1 responsible for MAP2 protein degradation through ubiquitin-proteasome pathway in rat hippocampal neurons
the enzymatic deamidation of N-terminal L-Asn by N-terminal asparagine amidohydrolase (NTAN1) is a feature of the ubiquitin-dependent N-end rule pathway of protein degradation, which relates the in vivo half-life of a protein to the identity of its N-terminal residue. hNTAN1 is shown to possess a critical Cys residue that is absolutely required for catalysis, corroborated in part by abolishment of activity through the Cys75Ala point mutation. The exposure of a conserved L-Pro at the N-terminus of hNTAN1 following removal of the initiating L-Met is important for the function of the enzyme
the N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. In mammals, the tertiary destabilizing N-terminal residues asparagine and glutamine function through their conversion, by enzymatic deamidation, into the secondary destabilizing residues aspartate and glutamate, whose destabilizing activity requires their enzymatic conjugation to arginine, one of the primary destabilizing residues. The NtN-amidase is a 310-residue amidohydrolase specific for N-terminal asparagine. Recombinant NtN-amidase retains its asparagine selectivity in vivo and can implement the asparagine-specific subset of the N-end rule
the N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. In mammals, the tertiary destabilizing N-terminal residues asparagine and glutamine function through their conversion, by enzymatic deamidation, into the secondary destabilizing residues aspartate and glutamate, whose destabilizing activity requires their enzymatic conjugation to arginine, one of the primary destabilizing residues. The NtN-amidase is a 310-residue amidohydrolase specific for N-terminal asparagine. Recombinant NtN-amidase retains its asparagine selectivity in vivo and can implement the asparagine-specific subset of the N-end rule
the N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. In mammals, the tertiary destabilizing N-terminal residues asparagine and glutamine function through their conversion, by enzymatic deamidation, into the secondary destabilizing residues aspartate and glutamate, whose destabilizing activity requires their enzymatic conjugation to arginine, one of the primary destabilizing residues. The NtN-amidase is a 310-residue amidohydrolase specific for N-terminal asparagine. Recombinant NtN-amidase retains its asparagine selectivity in vivo and can implement the asparagine-specific subset of the N-end rule
in solution, yNta1 is a monomer containing 14 beta-strands, 11 alpha-helices, and three 310-helices. The core region of the enzyme shows antiparallel and parallel mixed beta-sheets surrounded by helices, and these sixstranded beta-sheets face each other
construction and analysis of mouse strains lacking the asparagine-specific N-terminal amidase (NtN-amidase), encoded by the Ntan1 gene, by deletion-disruption of the mouse Ntan1 gene
construction and analysis of mouse strains lacking the asparagine-specific N-terminal amidase (NtN-amidase), encoded by the Ntan1 gene, by deletion-disruption of the mouse Ntan1 gene
recombinant mouse NtN-amidase enzyme expressed in an enzyme-mutant Saccharomyces cerevisiae strain can implement the asparagine-specific subset of the yeast N-end rule
recombinant mouse NtN-amidase enzyme expressed in an enzyme-mutant Saccharomyces cerevisiae strain can implement the asparagine-specific subset of the yeast N-end rule
recombinant mouse NtN-amidase enzyme expressed in an enzyme-mutant Saccharomyces cerevisiae strain can implement the asparagine-specific subset of the yeast N-end rule
construction and analysis of mouse strains lacking the asparagine-specific N-terminal amidase (NtN-amidase), encoded by the Ntan1 gene, by deletion-disruption of the mouse Ntan1 gene
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
native enzyme 11515fold to homogeneity from liver by anion exchange chromatography, ammonium sulfate fractionation, gel filtration, and another step of anion exchange chromatgraphy, follwed by chromatofocusing and again gel filtration
recombinant tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by affinity cromatography and ultrafiltration, method improvement
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene Ntan1 gene is located in the proximal region of mouse chromosome 16 and contains 10 exons ranging from 54 to 177 base pairs in length, recombinant expression of mouse NtN-amidase in Saccharomyces cerevisiae nta1DELTA enzyme-deficient strain
gene Ntan1, DNA and amino acid sequence determination and analysis, Ntan1 promoter identification, chromosome mapping of gene Ntan1 reveals that Ntan1 is located in the proximal region of mouse chromosome 16, the gene is located in the proximal region of mouse chromosome 16 and contains 10 exons ranging from 54 to 177 base pairs in length, recombinant expression of full-length mouse NtN-amidase in Saccharomyces cerevisiae nta1DELTA enzyme-deficient strain
gene NTAN1, phylogenetic analysis, recombinant expression of N-terminally His6-tagged wild-type and mutant enzymes with a C-terminal strepII-tag or a FLAG-strepII tandem affinity tag in Escherichia coli strain BL21(DE3), method improvement
gene Ntan1, rat Ntan1 promoter (-1361 to +99) is prepared from rat genomic DNA by PCR, sequence comparisons, overexpression of Ntan1 using recombinant Ntan1 adenovirus vector resulting in a marked decrease in the MAP2 protein expression in hippocampal neurons
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
gene Ntan1 mRNA is increased about 3fold after 3 h in response to brief magnetism. Brief magnetism also increases the transcriptional activity of Ntan1 promoter by luciferase reporter assay
Hirai, T.; Taniura, H.; Goto, Y.; Ogura, M.; Sng, J.; Yoneda, Y.
Stimulation of ubiquitin-proteasome pathway through the expression of amidohydrolase for N-terminal asparagine (Ntan1) in cultured rat hippocampal neurons exposed to static magnetism