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Literature summary extracted from

  • Vo, T.T.L.; Park, J.H.; Lee, E.J.; Nguyen, Y.T.K.; Han, B.W.; Nguyen, H.T.T.; Mun, K.C.; Ha, E.; Kwon, T.K.; Kim, K.W.; Jeong, C.H.; Seo, J.H.
    Characterization of lysine acetyltransferase activity of recombinant human ARD1/NAA10 (2020), Molecules, 25, 588 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.3.1.48 gene NAA10, recombinant expression of His-tagged ARD1/Naa10 in Escherichia coli strain BL21, recombinant expression of GST-tagged enzyme in Escherichia coli strain BL21 Homo sapiens
2.3.1.48 recombinant expression of His-tagged hARD1/NAA10 Homo sapiens
2.3.1.255 gene NAA10, recombinant expression of His-tagged ARD1/Naa10 in Escherichia coli strain BL21, recombinant expression of GST-tagged enzyme in Escherichia coli strain BL21 Homo sapiens
2.3.1.255 recombinant expression of His-tagged hARD1/NAA10 Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.3.1.48 K136R site-directed mutagenesis, mutant K136R fails to acetylate itself Homo sapiens
2.3.1.48 K136R site-directed mutagenesis, that lacks autoacetylation, the mutant shows wild-type NAT activity Homo sapiens
2.3.1.48 R82A/Y122F site-directed mutagenesis, the dominant-negative (DN) mutant lacks acetyltransferase activity. The DN mutant includes two mutations R82A and Y122F, which inhibit the binding of acetyl-CoA to hARD1/NAA10 and consequently suppresses its acetyltransferase activity. The DN mutant fails to acetylate itself Homo sapiens
2.3.1.48 R82A/Y122F site-directed mutagenesis, the mutant shows highly reduced NAT activity compared to wild-type Homo sapiens
2.3.1.255 K136R site-directed mutagenesis, that lacks autoacetylation, the mutant shows wild-type NAT activity Homo sapiens
2.3.1.255 K136R site-directed mutagenesis, the non-acetylated K136R mutant shows N-terminal acetyltransferase capacity as strongly as the hARD1/NAA10 wild-type, but fails to acetylate itself Homo sapiens
2.3.1.255 R82A/Y122F site-directed mutagenesis, the mutant shows highly reduced NAT activity compared to wild-type Homo sapiens
2.3.1.255 R82A/Y122F the acetyltransferase dead DN mutant of hARD1/NAA10 almost loses its NAT activity and fails to acetylate itself. The DN mutant includes two mutations R82A and Y122F, which inhibit the binding of acetyl-CoA to hARD1/NAA10 and consequently suppresses its acetyltransferase activity Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.3.1.48 acetyl-CoA + N-terminal L-lysyl-[beta-catenin] Homo sapiens
-
 CoA + H+ + N-terminal Nalpha-acetyl-lysyl-[beta-catenin]
-
 ir
2.3.1.48 acetyl-CoA + N-terminal L-lysyl-[Hsp70] Homo sapiens
-
 CoA + H+ + N-terminal Nalpha-acetyl-L-lysyl-[Hsp70]
-
 ir
2.3.1.48 acetyl-CoA + [protein]-L-lysine Homo sapiens
-
 CoA + [protein]-N6-acetyl-L-lysine
-
 ?
2.3.1.255 acetyl-CoA + an N-terminal-amino acid-[protein] Homo sapiens
-
 an N-terminal-Nalpha-acetyl-amino acid-[protein] + CoA
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.3.1.48 Homo sapiens P41227
-
-
2.3.1.255 Homo sapiens P41227
-
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
2.3.1.48 acetylation hARD1/NAA10 undergoes autoacetylation at residue K136, which is critical to stimulate its lysine acetyltransferase (KAT) activity. Recombinant hARD1 has the tendency to lose its lysine acetylation activity in vitro. The autoacetylation is not required for NAT activity of ARD1/Naa10 Homo sapiens
2.3.1.48 acetylation hARD1/NAA10 undergoes autoacetylation, which is critical to stimulate its KAT activity. In vitro, the autoacetylation activity of purified hARD1 fails to last long. hARD1/NAA10 is known to acetylate its K136 lysine residue, and K136 acetylation is important to stimulate its KAT activity. The enzyme K136R and DN mutants fail to acetylate themselves Homo sapiens
2.3.1.255 acetylation hARD1/NAA10 undergoes autoacetylation at residue K136, which is critical to stimulate its lysine acetyltransferase (KAT) activity. Recombinant hARD1 has the tendency to lose its lysine acetylation activity in vitro. The autoacetylation is not required for NAT activity of ARD1/Naa10 Homo sapiens
2.3.1.255 acetylation hARD1/NAA10 undergoes autoacetylation, which is critical to stimulate its KAT activity. In vitro, the autoacetylation activity of purified hARD1 fails to last long Homo sapiens

Purification (Commentary)

EC Number Purification (Comment) Organism
2.3.1.48 recombinant His-tagged ARD1/Naa10 from Escherichia coli by nickel affinity chromatography, anion exchange chromatography, and gel filtration. After purification, rhARD1/NAA10 mainly exists in a high oligomeric state and has only a few monomers. Recombinant GST-tagged enzyme from Escherichia coli strain BL21 by glutathione affinity chromatography Homo sapiens
2.3.1.48 recombinant His-tagged hARD1/NAA10 enzyme by nickel affinity chromatography, with or without anion exchange chromatography, followed by gel filtration, and dialysis, the lysine acetylation activity of hARD1/NAA10 is well maintained until the elution step, but dramatically diminished after overnight dialysis. rhARD1/NAA10 aggregates during purification Homo sapiens
2.3.1.255 recombinant His-tagged ARD1/Naa10 from Escherichia coli by nickel affinity chromatography, anion exchange chromatography, and gel filtration. After purification, rhARD1/NAA10 mainly exists in a high oligomeric state and has only a few monomers. Recombinant GST-tagged enzyme from Escherichia coli strain BL21 by glutathione affinity chromatography Homo sapiens
2.3.1.255 recombinant His-tagged hARD1/NAA10 enzyme by nickel affinity chromatography, with or without anion exchange chromatography, followed by gel filtration, and dialysis, rhARD1/NAA10 aggregates during purification Homo sapiens

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.1.48 acetyl-CoA + N-terminal L-lysyl-[beta-catenin]
-
 Homo sapiens CoA + H+ + N-terminal Nalpha-acetyl-lysyl-[beta-catenin]
-
 ir
2.3.1.48 acetyl-CoA + N-terminal L-lysyl-[Hsp70]
-
 Homo sapiens CoA + H+ + N-terminal Nalpha-acetyl-L-lysyl-[Hsp70]
-
 ir
2.3.1.48 acetyl-CoA + N-terminal L-lysyl-[Hsp70] acetylation of residue K77 Homo sapiens CoA + H+ + N-terminal Nalpha-acetyl-L-lysyl-[Hsp70]
-
 ir
2.3.1.48 acetyl-CoA + [Hsp70]-L-lysine difference in the acetylation of Hsp70 with or without rhARD1 can be observed at low ratio of enzyme: substrate up to 1:25 but not at that of higher ratio over 1:25. The enzyme targets Lys77 of Hsp70, the hARD1/NAA10-mediated catalysis of Hsp70 is abolished with K77R mutation in Hsp70 Homo sapiens CoA + [Hsp70]-N6-acetyl-L-lysine
-
 ?
2.3.1.48 acetyl-CoA + [protein]-L-lysine
-
 Homo sapiens CoA + [protein]-N6-acetyl-L-lysine
-
 ?
2.3.1.48 additional information lysine acetyltransferase (KAT) activity of recombinant human ARD1/NAA10, overview. Arrest defective 1 (ARD1) is the only enzyme known so far to exhibit both N-terminal acetyltransferase (NAT) and N-terminal lysine acetyltransferase (KAT) activities. Only the monomeric rhARD1/NAA10 form, but not the oligomeric form, can acetylate lysine residues of substrate proteins. rhARD1/NAA10-mediated Hsp70 acetylation increased in a time-dependent manner Homo sapiens ?
-
-
2.3.1.48 additional information recombinant hARD1/NAA10 exhibits KAT activity, which disappears soon in vitro due to enzyme oligomerization, which results in the loss of KAT activity. While oligomeric recombinant hARD1/NAA10 loses its ability for lysine acetylation, its monomeric form clearly exhibits lysine acetylation activity in vitro. Assay optimization, under optimal conditions, hARD1/NAA10 retains its KAT activity, overview Homo sapiens ?
-
-
2.3.1.255 acetyl-CoA + an N-terminal-amino acid-[protein]
-
 Homo sapiens an N-terminal-Nalpha-acetyl-amino acid-[protein] + CoA
-
 ?
2.3.1.255 acetyl-CoA + N-terminal L-aspartyl-[DDIAALRWGRPVGRRRRPVRVYP]
-
 Homo sapiens CoA + H+ + N-terminal Nalpha-acetyl-L-aspartyl-[DDIAALRWGRPVGRRRRPVRVYP]
-
 ir
2.3.1.255 acetyl-CoA + N-terminal L-glutamyl-[EEIAALRWGRPVGRRRRPVRVYP]
-
 Homo sapiens CoA + H+ + N-terminal Nalpha-acetyl-L-glutamyl-[EEIAALRWGRPVGRRRRPVRVYP]
-
 ir
2.3.1.255 additional information lysine acetyltransferase (KAT) activity of recombinant human ARD1/NAA10, overview. Arrest defective 1 (ARD1) is the only enzyme known so far to exhibit both N-terminal acetyltransferase (NAT) and N-terminal lysine acetyltransferase (KAT) activities. Only the monomeric rhARD1/NAA10 form, but not by the oligomeric form, can acetylate lysine residues of substrate proteins Homo sapiens ?
-
-
2.3.1.255 additional information recombinant hARD1/NAA10 exhibits KAT activity, which disappears soon in vitro due to enzyme oligomerization, which results in the loss of KAT activity. While oligomeric recombinant hARD1/NAA10 loses its ability for lysine acetylation, its monomeric form clearly exhibits lysine acetylation activity in vitro. Assay optimization, under optimal conditions, hARD1/NAA10 retains its KAT activity, overview Homo sapiens ?
-
-

Subunits

EC Number Subunits Comment Organism
2.3.1.48 monomer active form Homo sapiens
2.3.1.48 More size-exclusion analysis reveals that most recombinant hARD1/NAA10 form oligomers over time, resulting in the loss of KAT activity. After purification, rhARD1/NAA10 mainly exists in a high oligomeric state and has only a few monomers. The NAT activity is highest for the monomeric enzyme, about 2fold higher compared to the oligomeric enzyme and about 20% higher compared to the dimeric enzyme Homo sapiens
2.3.1.48 More the oligomeric recombinant hARD1/NAA10 loses the ability for lysine acetylation, while the monomeric form clearly shows lysine acetylation activity in vitro Homo sapiens
2.3.1.255 monomer active form Homo sapiens
2.3.1.255 More size-exclusion analysis reveals that most recombinant hARD1/NAA10 form oligomers over time, resulting in the loss of KAT activity. After purification, rhARD1/NAA10 mainly exists in a high oligomeric state and has only a few monomers. The NAT activity is highest for the monomeric enzyme, about 2fold higher compared to the oligomeric enzyme and about 20% higher compared to the dimeric enzyme Homo sapiens
2.3.1.255 More the oligomeric recombinant hARD1/NAA10 loses the ability for lysine acetylation, while the monomeric form clearly shows lysine acetylation activity in vitro Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
2.3.1.48 ARD1
-
 Homo sapiens
2.3.1.48 arrest defective 1
-
 Homo sapiens
2.3.1.48 hARD1
-
 Homo sapiens
2.3.1.48 KAT
-
 Homo sapiens
2.3.1.48 lysine acetyltransferase
-
 Homo sapiens
2.3.1.48 More see also EC 2.3.1.255 Homo sapiens
2.3.1.48 N(alpha)-acetyltransferase 10
-
 Homo sapiens
2.3.1.48 N-terminal acetyltransferase
-
 Homo sapiens
2.3.1.48 NAA10
-
 Homo sapiens
2.3.1.48 NAT
-
 Homo sapiens
2.3.1.255 ARD1
-
 Homo sapiens
2.3.1.255 arrest defective 1
-
 Homo sapiens
2.3.1.255 hARD1
-
 Homo sapiens
2.3.1.255 More see also EC 2.3.1.48 Homo sapiens
2.3.1.255 N(alpha)-acetyltransferase 10
-
 Homo sapiens
2.3.1.255 N-terminal acetyltransferase
-
 Homo sapiens
2.3.1.255 N-terminal acetyltransferase 10
-
 Homo sapiens
2.3.1.255 NAA10
-
 Homo sapiens
2.3.1.255 NAT
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.3.1.48 37
-
 assay at Homo sapiens
2.3.1.255 37
-
 assay at Homo sapiens

Temperature Stability [°C]

EC Number Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
2.3.1.48 95
-
 30 min, inactivation Homo sapiens
2.3.1.255 95
-
 30 min, inactivation Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.3.1.48 8
-
-
 Homo sapiens
2.3.1.48 8
-
 assay at Homo sapiens
2.3.1.255 8
-
-
 Homo sapiens
2.3.1.255 8
-
 assay at Homo sapiens

pH Range

EC Number pH Minimum pH Maximum Comment Organism
2.3.1.48 8 9 activity range, inactive below Homo sapiens
2.3.1.255 8 9 activity range, inactive below Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
2.3.1.48 acetyl-CoA
-
 Homo sapiens
2.3.1.255 acetyl-CoA
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
2.3.1.48 malfunction inhibition of hARD1/NAA10 autoacetylation by K136R mutation induces the drop of KAT activity, but not NAT activity. Heat-induced disruption of hARD1/NAA10 structure also diminishes its lysine acetylation activity Homo sapiens
2.3.1.48 malfunction oligomerization results in the loss of KAT activity Homo sapiens
2.3.1.48 additional information the NAT activity is highest for the monomeric enzyme, about 2fold higher compared to the oligomeric enzyme and about 20% higher compared to the dimeric enzyme Homo sapiens
2.3.1.48 physiological function arrest defective 1 (ARD1), also known as N(alpha)-acetyltransferase 10 (NAA10) is originally identified as an N-terminal acetyltransferase (NAT) that catalyzes the acetylation of N-termini of newly synthesized peptides. Mammalian ARD1/NAA10 also plays a roleas lysine acetyltransferase (KAT) that posttranslationally acetylates internal lysine residues of proteins. ARD1/NAA10 is the only enzyme with both NAT (EC 2.3.1.255) and KAT (EC 2.3.1.48) activities. NATs acetylate N-terminal residues of newly synthesized proteins from ribosomes in an irreversible manner. N-terminal acetylation is known to be closely related to protein stability, interaction, and localization. lysine acetylation catalyzed by KATs is reversibly regulated by lysine deacetyltransferases (KDACs) that remove acetyl groups from lysine residues in proteins. While acetylation neutralizes the positive charge on lysine residues, deacetylation recovers it, thereby causing a change in electronic and conformational properties of proteins. Acetylation and deacetylation of lysine residues serve as the switches that turn-on and turn-off the cellular signal pathways and regulate diverse biological events. Any unbalance between lysine acetylation and deacetylation results in the improper regulation of biological processes and may cause various types of human diseases such as cancer and neurodegeneration Homo sapiens
2.3.1.48 physiological function N-terminal acetylation catalyzed by NATs is one of the most common protein modifications in eukaryotes, affecting about 80% human proteins. In general, NATs acetylate N-terminal residues of newly synthesized proteins from ribosomes in an irreversible manner. N-terminal acetylation is known to be closely related to protein stability, interaction, and localization. Human ARD1/NAA10 expanded its' role to lysine acetyltransferase (KAT) that post-translationally acetylates internal lysine residues of proteins. Size-exclusion analysis reveals that most recombinant hARD1/NAA10 forms oligomers. While oligomeric recombinant hARD1/NAA10 loses its ability for lysine acetylation, its monomeric form clearly exhibits lysine acetylation activity in vitro. In contrast to N-terminal acetylation, lysine acetylation catalyzed by KATs is reversibly regulated by lysine deacetyltransferases (KDACs) that remove acetyl groups from lysine residues in protein. hARD1 regulates a wide range of cellular functions, including cell cycle, apoptosis, migration, stress response, and differentiation. NAT and KAT activity might be independently regulated, relying on the interaction partners Homo sapiens
2.3.1.255 malfunction inhibition of hARD1/NAA10 autoacetylation by K136R mutation induces the drop of KAT activity, but not NAT activity Homo sapiens
2.3.1.255 malfunction oligomerization results in the loss of KAT activity Homo sapiens
2.3.1.255 additional information the NAT activity is highest for the monomeric enzyme, about 2fold higher compared to the oligomeric enzyme and about 20% higher compared to the dimeric enzyme Homo sapiens
2.3.1.255 physiological function arrest defective 1 (ARD1), also known as N(alpha)-acetyltransferase 10 (NAA10) is originally identified as an N-terminal acetyltransferase (NAT) that catalyzes the acetylation of N-termini of newly synthesized peptides. Mammalian ARD1/NAA10 also plays a role as lysine acetyltransferase (KAT) that posttranslationally acetylates internal lysine residues of proteins. ARD1/NAA10 is the only enzyme with both NAT (EC 2.3.1.255) and KAT (EC 2.3.1.48) activities. NATs acetylate N-terminal residues of newly synthesized proteins from ribosomes in an irreversible manner. N-terminal acetylation is known to be closely related to protein stability, interaction, and localization. lysine acetylation catalyzed by KATs is reversibly regulated by lysine deacetyltransferases (KDACs) that remove acetyl groups from lysine residues in proteins. While acetylation neutralizes the positive charge on lysine residues, deacetylation recovers it, thereby causing a change in electronic and conformational properties of proteins. Acetylation and deacetylation of lysine residues serve as the switches that turn-on and turn-off the cellular signal pathways and regulate diverse biological events. Any unbalance between lysine acetylation and deacetylation results in the improper regulation of biological processes and may cause various types of human diseases such as cancer and neurodegeneration Homo sapiens
2.3.1.255 physiological function N-terminal acetylation catalyzed by NATs is one of the most common protein modifications in eukaryotes, affecting about 80% human proteins. In general, NATs acetylate N-terminal residues of newly synthesized proteins from ribosomes in an irreversible manner. N-terminal acetylation is known to be closely related to protein stability, interaction, and localization. Human ARD1/NAA10 expanded its' role to lysine acetyltransferase (KAT) that post-translationally acetylates internal lysine residues of proteins. Size-exclusion analysis reveals that most recombinant hARD1/NAA10 forms oligomers While oligomeric recombinant hARD1/NAA10 loses its ability for lysine acetylation, its monomeric form clearly exhibited lysine acetylation activity in vitro. In contrast to N-terminal acetylation, lysine acetylation catalyzed by KATs is reversibly regulated by lysine deacetyltransferases (KDACs) that remove acetyl groups from lysine residues in protein. hARD1 regulates a wide range of cellular functions, including cell cycle, apoptosis, migration, stress response, and differentiation. NAT and KAT activity might be independently regulated, relying on the interaction partners Homo sapiens