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IUBMB CommentsN-terminal-acetylases (NATs) catalyse the covalent attachment of an acetyl moiety from acetyl-CoA to the free alpha-amino group at the N-terminus of a protein. This irreversible modification neutralizes the positive charge at the N-terminus and makes the N-terminal residue larger and more hydrophobic. The NatA complex is found in all eukaryotic organisms, and specifically targets N-terminal Ala, Gly, Cys, Ser, Thr, and Val residues, that became available after removal of the initiator methionine.
Synonyms
naa15, ard1b, hnaa10,
daf-31, naa11, n-terminal acetyltransferase a, arrest-defective protein 1, mtrimi, ta0058, n-alpha-acetyltransferase,
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acetyl-CoA:N-terminal-Gly/Ala/Ser/Val/Cys/Thr-[protein] Nalpha-acetyltransferase
N-terminal-acetylases (NATs) catalyse the covalent attachment of an acetyl moiety from acetyl-CoA to the free alpha-amino group at the N-terminus of a protein. This irreversible modification neutralizes the positive charge at the N-terminus and makes the N-terminal residue larger and more hydrophobic. The NatA complex is found in all eukaryotic organisms, and specifically targets N-terminal Ala, Gly, Cys, Ser, Thr, and Val residues, that became available after removal of the initiator methionine.
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acetyl-CoA + [Runx2]
[Runx2]-N-terminal-N6-acetyl-L-lysine + CoA
NAA10 acetylates Runx2 at Lys225
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acetyl-CoA + an N-terminal-lysinyl-[androgen receptor]
an N-terminal-Nalpha-acetyl-lysinyl-[androgen receptor] + CoA
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ARD1 acetylates androgen receptor at lysine 618
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ARD1 and NAT1 constitute an N-acetyltransferase complex where ARD1 holds the enzymatic activity of the complex. The ARD1-NAT1 complex mediates N-terminal acetylation of nascent polypeptides that emerge from ribosomes after translation. ARD1 may also acetylate the internal lysine residues of proteins
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acetylation of alpha-tubulin
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acetylation of alpha-tubulin
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caudal half region, immortalized embryonic endothelial cells
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immortalized embryonic endothelial cells
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NAA10 expression decreases with the induction of differentiation in NB4 cells, but the level of NAA11 remains unchanged
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Naa10 is expressed in premeiotic spermatogonia
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NAA11, a homologue of NAA10, is predominantly expressed in mouse testis. NAA10 and NAA11 display opposite expression patterns during spermatogenesis
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during brain development in mouse, Naa10 and Naa15 (the auxiliary subunit of NatA) are highly expressed in regions rich in proliferating and migrating cells, such as the ventricular zone, neocortex, olfactory bulb, and hippocampus. The expression of both genes is downregulated as neurons differentiate and mitotic and migratory activities subside. Then, once again, their expression increases during postnatal development in the hippocampus and during the neuronal dendritic development of Purkinje cells (PCs) in the cerebellum. This finding indicates that the regulation of expression of both genes is related to neuronal development, especially in the hippocampus and in the PCs of the cerebellum
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NAA11, a homologue of NAA10, is predominantly expressed in mouse testis
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additional information
tissue-specific expression of Naa10 during different developmental stages in C57BL6/J mice
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tissue-specific expression of Naa10 during different developmental stages in C57BL6/J mice
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NAA10 and NAA11 display opposite expression patterns during spermatogenesis. No expression of Naa11 in premeiotic spermatogonia
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additional information
NAA10 and NAA11 display opposite expression patterns during spermatogenesis. No expression of Naa11 in premeiotic spermatogonia
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metabolism
ARD1 variants have different effects on hypoxia-inducible factor-1alpha stability and acetylation
physiological function
importance of NAA10 catalytic activity in mouse development. The potential role of NAA10 varies depending on transcriptional levels in different tissues and embryonic stages during development. Naa10 homologue Naa11 has a role in the cellular differentiation process while Naa10 has a role in the cellular proliferation process. The differential expression pattern of Naa10 and Naa11 suggests that Naa11 is complementary to Naa10 at least in the mice and that its biological role can be important in spermiogenesis or cellular processes
malfunction
Aenzyme knockdown significantly reduces dendritic extension in cultured Purkinje cells
malfunction
measuring the different time points of gene expression upon Naa10 siRNA treatment, NTN1 and its receptor UNC5B are found to be the most dramatically overexpressed among the genes involved in morphogenesis
malfunction
overexpression of Naa10 in mice results in the delayed closure of calvarial fontanels and reduced bone density, osteoblast surfaces and mRNA levels of the osteoblastogenic genes in calvaria. In contrast, Naa10 deficient mice display calvarial and femoral bone development to a greater extent on postnatal day 3
physiological function
the ARD1-NAT1 complex has acetyltransferase activity against microtubules in dendrites and regulates dendritic arborization in neuronal cells
physiological function
the enzyme controls osteoblast differentiation and bone formation as a feedback regulator of Runt-related transcription factor 2
physiological function
importance of NAA10 catalytic activity in mouse development. The potential role of NAA10 varies depending on transcriptional levels in different tissues and embryonic stages during development. Naa10 homologue Naa11 has a role in the cellular differentiation process while Naa10 has a role in the cellular proliferation process. The differential expression pattern of Naa10 and Naa11 suggests that Naa11 is complementary to Naa10 at least in the mice and that its biological role can be important in spermiogenesis or cellular processes. Naa10 is known to regulate cellular processes, and its effects are not only catalyzed through its major activity as a NAT but also through the N-epsilon-acetylation of several proteins. The N-epsilon-acetyl-activity of Naa10 requires auto-acetylation. This requirement is similar to that of other acetyltransferases, which acetylate themselves for their catalytic and functional activities. Naa10 plays an important role in osteoblast differentiation and the early phases of bone formation. Naa10 counteracts HDAC6 by acetylating alpha-tubulin, thereby promoting MT stability for dendritic development
physiological function
N-alpha-acetyltransferase 10 (Naa10) is the catalytic subunit of N-acetyltransferase A (NatA), it catalyzes N-alpha-acetylation, epsilon-acetylation, as well as autoacetylation. The alpha (N-terminal) acetyltransferase functions as a major modulator of cell growth and differentiation. Potential function of Naa10 in cell morphogenesis. Negative regulation of Naa10 towards NTN1 and its receptor UNC5B are detected upon treatment of all-trans retinoid acid, usedto induce morphological differentiation. UNC-5 Homolog B (UNC5b), a dependence receptor of netrin-1, plays an essential role in mediating the repulsive effect of axonal migration and blood vessel formation through association with its ligand netrin-1 (NTN1). In addition, UNC5B has also been indicated as a putative tumor suppressor gene in numerous cancers
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Sugiura, N.; Adams, S.M.; Corriveau, R.A.
An evolutionarily conserved N-terminal acetyltransferase complex associated with neuronal development
J. Biol. Chem.
278
40113-40120
2003
Mus musculus
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Ohkawa, N.; Sugisaki, S.; Tokunaga, E.; Fujitani, K.; Hayasaka, T.; Setou, M.; Inokuchi, K.
N-acetyltransferase ARD1-NAT1 regulates neuronal dendritic development
Genes Cells
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1171-1183
2008
Mus musculus (Q9QY36)
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Kim, S.H.; Park, J.A.; Kim, J.H.; Lee, J.W.; Seo, J.H.; Jung, B.K.; Chun, K.H.; Jeong, J.W.; Bae, M.K.; Kim, K.W.
Characterization of ARD1 variants in mammalian cells
Biochem. Biophys. Res. Commun.
340
422-427
2006
Homo sapiens (P41227), Mus musculus (Q9QY36)
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Yoon, H.; Kim, H.L.; Chun, Y.S.; Shin, D.H.; Lee, K.H.; Shin, C.S.; Lee, D.Y.; Kim, H.H.; Lee, Z.H.; Ryoo, H.M.; Lee, M.N.; Oh, G.T.; Park, J.W.
NAA10 controls osteoblast differentiation and bone formation as a feedback regulator of Runx2
Nat. Commun.
5
5176
2014
Mus musculus (Q9QY36)
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DePaolo, J.S.; Wang, Z.; Guo, J.; Zhang, G.; Qian, C.; Zhang, H.; Zabaleta, J.; Liu, W.
Acetylation of androgen receptor by ARD1 promotes dissociation from HSP90 complex and prostate tumorigenesis
Oncotarget
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71417-71428
2016
Mus musculus
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Lee, M.N.; Kweon, H.Y.; Oh, G.T.
N-alpha-acetyltransferase 10 (NAA10) in development the role of NAA10
Exp. Mol. Med.
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1-11
2018
Arabidopsis thaliana (Q9FKI4), Caenorhabditis elegans (O61219), Caenorhabditis elegans DAF-31 (O61219), Danio rerio (Q7T3B8), Drosophila melanogaster (Q9VT75), Homo sapiens (P41227), Mus musculus (Q3UX61), Mus musculus (Q9QY36), Mus musculus C57Bl6/J (Q3UX61), Mus musculus C57Bl6/J (Q9QY36), Saccharomyces cerevisiae (P07347 AND P12945), Saccharomyces cerevisiae ATCC 204508 (P07347 AND P12945), Trypanosoma brucei (Q9NFL8)
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Xu, H.; Han, Y.; Liu, B.; Li, R.
Unc-5 homolog B (UNC5B) is one of the key downstream targets of N-alpha-acetyltransferase 10 (Naa10)
Sci. Rep.
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38508
2016
Homo sapiens (P41227), Mus musculus (Q9QY36), Mus musculus C57 (Q9QY36)
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