Any feedback?
Information on EC 2.3.1.255 - N-terminal amino-acid Nalpha-acetyltransferase NatA and Organism(s) Homo sapiens and UniProt Accession P41227
for references in articles please use BRENDA:EC2.3.1.255Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
2.3.1.255 N-terminal amino-acid Nalpha-acetyltransferase NatAIUBMB Comments
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.
Specify your search results
Word Map
- 2.3.1.255
-
auxiliary
- n-acetyltransferase
-
n-termini
-
ogden
-
co-translationally
-
n-alpha-acetylation
- hypk
-
cotranslation
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
hide(3 overall reactions are displayed. Show all (6)>>)
+
an N-terminal-glycyl-[protein]
=
an N-terminal-Nalpha-acetyl-glycyl-[protein]
+
+
an N-terminal-L-alanyl-[protein]
=
an N-terminal-Nalpha-acetyl-L-alanyl-[protein]
+
+
an N-terminal-L-seryl-[protein]
=
an N-terminal-Nalpha-acetyl-L-seryl-[protein]
+
Synonyms
naa15, ard1b, hnaa10, naa11, daf-31, n-terminal acetyltransferase a, arrest-defective protein 1, mtrimi, ta0058, n-alpha-acetyltransferase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
NAA10
ARD1
NAA10
NAA15
NatA
ARD1
-
-
-
-
NAA10
-
-
-
-
NAA15
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
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.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + an N-terminal-amino acid-[protein]
an N-terminal-Nalpha-acetyl-amino acid-[protein] + CoA
-
-
-
?
acetyl-CoA + N-terminal L-aspartyl-[DDIAALRWGRPVGRRRRPVRVYP]
CoA + H+ + N-terminal Nalpha-acetyl-L-aspartyl-[DDDIAALRWGRPVGRRRRPVRVYP]
-
-
-
?
acetyl-CoA + N-terminal L-aspartyl-[DDIAALRWGRPVGRRRRPVRVYP]
CoA + H+ + N-terminal Nalpha-acetyl-L-aspartyl-[DDIAALRWGRPVGRRRRPVRVYP]
-
-
-
ir
acetyl-CoA + N-terminal L-glutamyl-[EEIAALRWGRPVGRRRRPVRVYP]
CoA + H+ + N-terminal Nalpha-acetyl-L-glutamyl-[EEEIAALRWGRPVGRRRRPVRVYP]
-
-
-
?
acetyl-CoA + N-terminal L-glutamyl-[EEIAALRWGRPVGRRRRPVRVYP]
CoA + H+ + N-terminal Nalpha-acetyl-L-glutamyl-[EEIAALRWGRPVGRRRRPVRVYP]
-
-
-
ir
acetyl-CoA + N-terminal L-methionyl-[LGPEGGRWGRPVGRRRRPVRVYP]
CoA + H+ + N-terminal Nalpha-acetyl-L-methionyl-[MLGPEGGRWGRPVGRRRRPVRVYP]
-
-
-
?
acetyl-CoA + N-terminal L-methionyl-[MMP2]
CoA + H+ + N-terminal Nalpha-acetyl-L-methionyl-[MMP2]
matrix metalloproteinase-2, MMP2, with sequence MEALMAR
-
-
?
acetyl-CoA + N-terminal L-seryl-[ESSSKSRWGRPVGRRRRPVRVYP]
CoA + H+ + N-terminal Nalpha-acetyl-L-seryl-[SESSSKSRWGRPVGRRRRPVRVYP]
-
-
-
?
acetyl-CoA + ACTH peptide
CoA + ?
-
17 amino acids are identical to the adrenocorticotropin (ACTH) peptide sequence, the ACTH-derived lysines are replaced by arginines to minimize any potential interference by Nalpha-acetylation
-
-
?
acetyl-CoA + an N-terminal-glycyl-[protein]
an N-terminal-Nalpha-acetyl-glycyl-[protein] + CoA
-
-
-
-
?
acetyl-CoA + an N-terminal-L-alanyl-[protein]
an N-terminal-Nalpha-acetyl-L-alanyl-[protein] + CoA
-
-
-
-
?
acetyl-CoA + an N-terminal-L-cysteinyl-[protein]
an N-terminal-Nalpha-acetyl-L-cysteinyl-[protein] + CoA
-
-
-
-
?
acetyl-CoA + an N-terminal-L-seryl-[protein]
an N-terminal-Nalpha-acetyl-L-seryl-[protein] + CoA
-
-
-
-
?
acetyl-CoA + an N-terminal-L-threonyl-[protein]
an N-terminal-Nalpha-acetyl-L-threonyl-[protein] + CoA
-
-
-
-
?
acetyl-CoA + an N-terminal-L-valyl-[protein]
an N-terminal-Nalpha-acetyl-L-valyl-[protein] + CoA
-
-
-
-
?
acetyl-CoA + N-terminal L-aspartyl-[DDIAALRWGRPVGRRRRPVRVYP]
CoA + H+ + N-terminal Nalpha-acetyl-L-aspartyl-[DDIAALRWGRPVGRRRRPVRVYP]
P41227; Q9BXJ9
-
-
-
?
acetyl-CoA + N-terminal L-glutamyl-[EEIAALRWGRPVGRRRRPVRVYP]
CoA + H+ + N-terminal Nalpha-acetyl-L-glutamyl-[EEIAALRWGRPVGRRRRPVRVYP]
P41227; Q9BXJ9
-
-
-
?
acetyl-CoA + N-terminal L-methionyl-[LGPEGGRWGRPVGRRRRPVRVYP]
CoA + H+ + N-terminal Nalpha-acetyl-L-methionyl-[LGPEGGRWGRPVGRRRRPVRVYP]
P41227; Q9BXJ9
-
-
-
?
acetyl-CoA + N-terminal L-seryl-[ESSSKSRWGRPVGRRRRPVRVYP]
CoA + H+ + N-terminal Nalpha-acetyl-L-seryl-[ESSSKSRWGRPVGRRRRPVRVYP]
acetyl-CoA + PCNP protein
CoA + Nalpha-acetyl-PCNP protein
-
i.e. PEST proteolytic signal-containing nuclear protein
-
-
?
acetyl-CoA + SESSSKSRWGRPVGRRRRPVRVYP
CoA + Ac-SESSSKSRWGRPVGRRRRPVRVYP
-
high-mobility-group protein A1 sequence
-
-
?
acetyl-CoA + N-terminal L-seryl-[ESSSKSRWGRPVGRRRRPVRVYP]
CoA + H+ + N-terminal Nalpha-acetyl-L-seryl-[ESSSKSRWGRPVGRRRRPVRVYP]
P41227; Q9BXJ9
-
-
-
?
acetyl-CoA + N-terminal L-seryl-[ESSSKSRWGRPVGRRRRPVRVYP]
CoA + H+ + N-terminal Nalpha-acetyl-L-seryl-[ESSSKSRWGRPVGRRRRPVRVYP]
P41227; Q9BXJ9
substrate SESS
-
-
?
additional information
?
-
Naa10 undergoes autoacetylation at lysine K136
-
-
?
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
-
-
-
additional information
?
-
no activity with an MMP2 mutated at the acetylytion site of Naa10
-
-
-
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
-
-
-
additional information
?
-
-
endogenous HYPK, a Huntingtin (Htt)-interacting protein, is a stable interactor of NatA, the C terminus of hNaa15p of NatA specifically interacts directly with HYPK, no interaction with hNaa25p of hNatB and hNaa35p of hNatC
-
-
?
additional information
?
-
enzyme variant ARD1131 has no autoacetylation activity
-
-
?
additional information
?
-
-
N-terminal acetyltransferase Naa10/ARD1 does not acetylate lysine residues
-
-
?
additional information
?
-
P41227; Q9BXJ9
N-terminal acetylation (NTA) is an irreversible protein modification
-
-
-
additional information
?
-
P41227; Q9BXJ9
substrates are SESS24 or EEEI24. The ability of NAA10-V111G to acetylate the acidic N-termini EEEI24 is highly reduced compared to wild-type enzyme
-
-
-
additional information
?
-
-
substrates are SESS24 or EEEI24. The ability of NAA10-V111G to acetylate the acidic N-termini EEEI24 is highly reduced compared to wild-type enzyme
-
-
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + an N-terminal-amino acid-[protein]
an N-terminal-Nalpha-acetyl-amino acid-[protein] + CoA
-
-
-
?
acetyl-CoA + an N-terminal-glycyl-[protein]
an N-terminal-Nalpha-acetyl-glycyl-[protein] + CoA
-
-
-
-
?
acetyl-CoA + an N-terminal-L-alanyl-[protein]
an N-terminal-Nalpha-acetyl-L-alanyl-[protein] + CoA
-
-
-
-
?
acetyl-CoA + an N-terminal-L-cysteinyl-[protein]
an N-terminal-Nalpha-acetyl-L-cysteinyl-[protein] + CoA
-
-
-
-
?
acetyl-CoA + an N-terminal-L-seryl-[protein]
an N-terminal-Nalpha-acetyl-L-seryl-[protein] + CoA
-
-
-
-
?
acetyl-CoA + an N-terminal-L-threonyl-[protein]
an N-terminal-Nalpha-acetyl-L-threonyl-[protein] + CoA
-
-
-
-
?
acetyl-CoA + an N-terminal-L-valyl-[protein]
an N-terminal-Nalpha-acetyl-L-valyl-[protein] + CoA
-
-
-
-
?
acetyl-CoA + PCNP protein
CoA + Nalpha-acetyl-PCNP protein
-
i.e. PEST proteolytic signal-containing nuclear protein
-
-
?
additional information
?
-
-
endogenous HYPK, a Huntingtin (Htt)-interacting protein, is a stable interactor of NatA, the C terminus of hNaa15p of NatA specifically interacts directly with HYPK, no interaction with hNaa25p of hNatB and hNaa35p of hNatC
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
hNAA50
P41227; Q9BXJ9
UniProt ID Q9GZZ1, HYPK and hNAA50 can bind to hNatA simultaneously to form a tetrameric hNatE/HYPK complex. NAA50 and HYPK exhibit negative cooperative binding to NAA15 in vitro and in human cells by inducing NAA15 shifts in opposing directions. hNAA50 and HYPK inhibit hNatA activity, and HYPK is dominant
-
HYPK
P41227; Q9BXJ9
UniProt ID Q9NX55, a protein with intrinsic NAA10 catalytic subunit inhibitory activity. HYPK and hNAA50 can bind to hNatA simultaneously to form a tetrameric hNatE/HYPK complex. NAA50 and HYPK exhibit negative cooperative binding to NAA15 in vitro and in human cells by inducing NAA15 shifts in opposing directions. hNAA50 and HYPK inhibit hNatA activity, and HYPK is dominant
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8.5
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
higher NAA10 transcripts in metastatic osteosarcoma tissues compared to non-metastatic tissues. MMP-2 expression levels are also significantly correlated with Naa10p levels in osteosarcoma tissues
additional information
additional information
enzyme levels in different osteosarcoma cell lines, overview
additional information
tissue-specific expression of Naa10 during different developmental stages in humans
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
the HYPK-hNatA interaction may occur at the ribosome, active translation is not obligatory for the interaction to occur. Thus, HYPK stably associates with hNatA, common binding to the ribosomes
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
evolution
P41227; Q9BXJ9
there are seven known NAT types (NatA through NatG), each composed of one or more specific subunits and having specific substrates defined by the very first amino acid residue (serine, alanine, etc.)
malfunction
metabolism
P41227; Q9BXJ9
the enzyme is involved in the co-translational N-terminal protein modification process, overview
physiological function
additional information
malfunction
knockdown of Naa10 in HeLa cells leads to apoptosis and sensitizes cells for daunorubicin-induced apoptosis
malfunction
mutations in N-terminal acetyltransferase Naa10 are the cause of Ogden Syndrome
malfunction
inactive Naa10 mutant S37Pw shows a phenotype with perinatal lethal disorder, hypotonia, global developmental delay, cryptorchidism, cardiac arrhythmias, skin laxity, dysmorphic features, hernias, and large fontanels. Naa10 mutant Y43S shows a phenotype with intellectual disability, facial dysmorphism, scoliosis, and long QT. Mutant R83C shows a phenootype with hypotonia, global developmental delay, dysmorphic features, autism spectrum disorder, epileptic encephalopathy, extrapyramidal signs, hypertension with left ventricular hypertrophy, thin corpus callosum, and progressive white matter loss. Mutations V107F and R116W cause phenotypes with severe global developmental delay with postnatal growth, skeletal anomalies, truncal hypotonia with hypertonia of the extremities, minor facial features, and behavioral anomalies. Mutation of residue F128 causes moderate to severe intellectually disability, feeding difficulties, eye anomalies, hypotonia, and developmental delay
malfunction
inhibition of hARD1/NAA10 autoacetylation by K136R mutation induces the drop of KAT activity, but not NAT activity
malfunction
knockdown and overexpression of Naa10p in osteosarcoma cells respectively leads to decreased and increased cell migratory/invasive abilities. Re-expression of Naa10p, but not of an enzymatically inactive mutant, relieves suppression of the invasive ability in vitro and metastasis in vivo imposed by Naa10p-knockdown. The matrix metalloproteinase (MMP)-2 is responsible for the Naa10p-induced invasive phenotype
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. Analysis of upregulated genes in Naa10 stably knocked down H1299 cell line, overview
malfunction
several X-linked NAA10 variants have been associated with genetic disorders. A NAA10 variant I72T with impaired acetyltransferase activity causes developmental delay, intellectual disability, and hypertrophic cardiomyopathy. Genotype-phenotype correlations for NAA10 variants, overview
metabolism
ARD1 variants have different effects on hypoxia-inducible factor-1alpha stability and acetylation
metabolism
Naa10 activates and/or amplifies the transcriptional activity of beta-catenin/TCF transcriptional activity thereby stimulating cyclin D1 and c-Myc expression leading to inhibition of p21WAF1/CIP1 and promoting the G1/S cell cycle transition. Naa10 is essential for the activation of caspase-2/-3/-7 and -9 in HeLa cells after doxorubicin stimulation
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
physiological function
importance of NAA10 catalytic activity in human development. The potential role of NAA10 varies depending on transcriptional levels in different tissues and embryonic stages during 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, used to 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
physiological function
N-alpha-acetyltransferase 10 protein (Naa10p) mediates N-terminal acetylation of nascent proteins. It promotes metastasis by stabilizing matrix metalloproteinase-2 protein in human osteosarcomas via its N-terminal acetylation activity. Oncogenic role of Naa10p, overview. Higher NAA10 transcripts are observed in metastatic osteosarcoma tissues compared to non-metastatic tissues and are also correlated with a worse prognosis of patients. Naa10p is directly associated with MMP-2 protein through its acetyltransferase domain and maintains MMP-2 protein stability via NatA complex activity. MMP-2 expression levels are also significantly correlated with Naa10p levels in osteosarcoma tissues. Function of Naa10p in the regulation of cell invasiveness by preventing MMP-2 protein degradation that is crucial during osteosarcoma metastasis. Naa10p promotes migratory/invasive abilities of osteosarcoma cells, it regulates cell invasion of the osteosarcoma cell lines
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
physiological function
the NAA10-NAA15 complex (NatA) is an N-terminal acetyltransferase that catalyzes N-terminal acetylation of about 40% of all human proteins. N-terminal acetylation has several different roles in the cell, including altering protein stability and degradation, protein localization and protein-protein interactions
malfunction
-
knockdown of acetyltransferase ARD1 significantly reduces the growth rate of human cancer cell lines. Furthermore, ARD1 knockdown induces apoptosis or sensitizes cells to drug induced apoptosis. Enzyme knockdown reduces the transcriptional activity of the beta-Catenin/TCF4 complex, downregulating cyclin D1 and thereby promoting G1-arrest and inhibition of cell proliferation of lung cancer cells
malfunction
P41227; Q9BXJ9
NAA10 germline variants are found in patients with the X-linked lethal Ogden syndrome, and in other familial or de novo cases with variable degrees of developmental delay, intellectual disability (ID) and cardiac anomalies. A R83H missense variant in NAA10 is detected by whole exome sequencing in two unrelated boys with intellectual disability, developmental delay, ADHD like behaviour, very limited speech and cardiac abnormalities. Phenotypes, overview. Mutant NAA10-R83H has a reduced monomeric catalytic activity, likely due to impaired enzyme-acetyl-CoA binding
malfunction
P41227; Q9BXJ9
NAA10 variants have been found in patients with an X-linked developmental disorder called Ogden syndrome in its most severe form and, in other familial or de novo cases, with variable degrees of syndromic intellectual disability (ID) affecting both sexes. The mutant NAA10-V111G has a reduced stability and 85% reduced monomeric catalytic activity, while catalytic NatA function remains unaltered. The syndromic cases may also require a degree of compromised NatA function. The Naa10-V111G phenotype shows mild/moderate non-syndromic intellectual disability, and delayed motor and language development, but normal behavior without autistic traits. The blood leukocyte X-inactivation pattern is within normal range (80/20)
physiological function
enzyme variant ARD1131 has no influence on cyclin D1 expression and cell growth
physiological function
-
the enzyme acts in complex with the NATH protein and catalyzes cotranslational acetylation of protein N-termini
physiological function
P41227; Q9BXJ9
hNatA significantly enhances the catalytic efficiency of hNatE (EC 2.3.1.258). The hNatE complex comprises subunits Naa10 and Naa15 (NatA) and Naa50. HYPK binding to hNatE largely nullifies this effect
physiological function
P41227; Q9BXJ9
N-terminal acetylation (NTA) is among the most widespread co-translational modifications found in eukaryotic proteins. NTA is carried out by N-terminal acetyltransferases (NATs), which catalyze the transfer of an acetyl moiety from acetyl coenzyme A to the N-terminal amino group of the nascent polypeptides as they emerge from the ribosome. NTA is estimated to affect up to 90% of human proteins and influences their folding, localization, complex formation, and degradation, along with a variety of cellular functions ranging from apoptosis to gene regulation. NTA is an irreversible protein modification
physiological function
P41227; Q9BXJ9
N-terminal acetylation is a common protein modification in human cells and is catalysed by N-terminal acetyltransferases (NATs), mostly cotranslationally. The NAA10-NAA15 (NatA) protein complex is the major NAT, responsible for acetylating about 40% of human protein. Naa15 is the NatA auxiliary subunit
physiological function
P41227; Q9BXJ9
the NAA10-NAA15 (NatA) protein complex is an N-terminal acetyltransferase responsible for acetylating about of eukaryotic proteins
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
additional information
P41227; Q9BXJ9
NatA homology modeling. Residue V111 is located towards the end of the beta5 strand, and a valine in this position is highly conserved in NAA10 homologues as well as in several other NAT catalytic subunits for which crystal structures have been solved. The side chain of V111 is forming a hydrophobic pocket together with Y145, M147, L119 and L109. It is also in close proximity to the sulfur group of acetyl-CoA, which seems to indicate a role for V111 in positioning of acetyl-CoA. A glycine in this position will not cause any steric clashes, but loss of the more bulky hydrophobic side chain of valine may possibly cause structural alterations affecting protein stability or AcCoA binding
additional information
-
NatA homology modeling. Residue V111 is located towards the end of the beta5 strand, and a valine in this position is highly conserved in NAA10 homologues as well as in several other NAT catalytic subunits for which crystal structures have been solved. The side chain of V111 is forming a hydrophobic pocket together with Y145, M147, L119 and L109. It is also in close proximity to the sulfur group of acetyl-CoA, which seems to indicate a role for V111 in positioning of acetyl-CoA. A glycine in this position will not cause any steric clashes, but loss of the more bulky hydrophobic side chain of valine may possibly cause structural alterations affecting protein stability or AcCoA binding
additional information
P41227; Q9BXJ9
structure comparison, wild-type NAA10 and mutant NAA10-R83H from the human NatA complex (PDB ID 6C9M) are compared with the structure of NAA10 from the Schizosaccharomyces pombe NatA complex (PDB ID 4KVM)
additional information
-
structure comparison, wild-type NAA10 and mutant NAA10-R83H from the human NatA complex (PDB ID 6C9M) are compared with the structure of NAA10 from the Schizosaccharomyces pombe NatA complex (PDB ID 4KVM)
additional information
P41227; Q9BXJ9
the NatA enzyme complex is composed of the subunits Naa10 and Naa15. ScNaa15 has a high degree of structural conservation with SpNaa15 and hNaa15 structures
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). NAA10_HUMAN
235
0
26459
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
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
additional information
the oligomeric recombinant hARD1/NAA10 loses the ability for lysine acetylation, while the monomeric form clearly shows lysine acetylation activity in vitro
additional information
P41227; Q9BXJ9
the NatA enzyme complex is composed of the subunits Naa10 and Naa15
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
acetylation
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
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
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
F128I
site-directed mutagenesis, the mutation leads an altered structure and reduced stability, and a dramatic recuction of Nt catalytic activity compared to wild-type
F128L
site-directed mutagenesis, the mutation leads an altered structure and reduced stability, and a dramatic recuction of Nt catalytic activity compared to wild-type
I72T
a naturally occuring mutation NAA10 c.215T>C, the mutant phenotype shows a milder phenotypic spectrum in comparison to most of the previously described patients with NAA10 variants. The three boys have development delay, intellectual disability, and cardiac abnormalities as overlapping phenotypes. NAA10 Ile72Thr protein is destabilized, while binding to NAA15 most likely is intact. The NatA activity of NAA10 Ile72Thr appears normal while its monomeric activity is decreased. Genotype-phenotype correlations for NAA10 variants, overview
K136R
R116W
site-directed mutagenesis, the mutation leads to a reduction in catalytic activity for the peptide substrates EEEI and SESS by 15% compared to wild-type
R82A/Y122F
R83C
site-directed mutagenesis, the mutation interferes with acetyl-CoA binding and leads to a 60% reduction in Nt-catalytic activity compared to wild-type
S37P
V107F
site-directed mutagenesis, the mutation leads to a reduction in catalytic activity for the peptide substrates EEEI and SESS by 95% compared to wild-type
Y43S
site-directed mutagenesis, the mutant is catalytically impaired in vitro, with approximately an 85% reduction in Nt-catalytic activity for peptide substrates EEEI, DDDI, and SESS
L814P
P41227; Q9BXJ9
site-directed mutagenesis, the hNAA15 mutant is defective for HYPK inhibition and reduces hNatA thermostability, hNAA10 binding is not affected. The hNAA15-L814P-V5 hNatA complex shows an increased catalytic activity compared to wild-type hNatA
R83H
P41227; Q9BXJ9
naturally occuring c.248G > A missense mutation, reduced enzymatic activity of monomeric NAA10-R83H. This variant is modelled to have an altered charge density in the acetyl-CoA binding region of NAA10
T406Y
P41227; Q9BXJ9
site-directed mutagenesis, the hNAA15-T406Y-V5 hNatA mutant complex displays a decreased catalytic activity toward the hNatA substrate SESS compared to wild-type hNatA. the hNAA15 mutant can disassociate hNAA50 from hNatA in vitro, hNAA10 binding is not affected
V111G
P41227; Q9BXJ9
a naturally occuring 332 T > G missense mutant, the mutant Naa10 has a reduced stability and 85% reduced monomeric catalytic activity, while catalytic NatA function remains unaltered. NAA10-V111G has a reduced stability compared to wild-type NAA10, and in vitro acetylation assays reveal a reduced enzymatic activity of monomeric NAA10-V111G but not for NAA10-V111G in complex with NAA15 (NatA enzymatic activity). A glycine in position 111 instead of valine will not cause any steric clashes, but loss of the more bulky hydrophobic side chain of valine may possibly cause structural alterations affecting protein stability or acetyl-CoA binding
additional information
K136R
site-directed mutagenesis, that lacks autoacetylation, the mutant shows wild-type NAT activity
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
R82A/Y122F
site-directed mutagenesis, the mutant shows highly reduced NAT activity compared to wild-type
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
S37P
site-directed mutagenesis, the mutant Naa10 protein shows reduced catalytic activity for EEEI, DDDI, and SESS peptide substrates, and inability to combine with Naa15. The mutant hNaa10 S37P recombinantly expressed in a NatA-defective Saccharomyces cerevisiae strain lacks a proper complex formation with hNaa15 and is reduced in in vitro catalytic activity
additional information
construction of Naa10 stably knocked down H1299 cell line H1299-shNaa10, cDNA microarray analysis
additional information
knockdown of Naa10p by shRNAs, knockdown efficiencies, overview. Generation of truncated Naa10p mutants
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant GST-tagged wild-type and mutant Naa10 enzymes from Escherichia coli strain BL21 by glutathione affinity chromatography
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
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
Ni-NTA resin column chromatography, Q ion exchange column chromatography, and S200 gel filtration
-
recombinant His-MBP-tagged wild-type and mutant Naa10 from Escherichia coli strain BL21 Star DE3 by affinity chromatography
P41227; Q9BXJ9
recombinant His-tagged and maltose binding protein-tagged subunits hNaa15p, hNaa10p, and hNaa50p from Escherichia coli by nickel affinity chromatography
-
recombinant His-tagged hNatA by affinity chromatography and gel filtration
P41227; Q9BXJ9
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene NAA10, real-time reverse transcription-PCR enzyme expression analysis
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
gene NAA10, recombinant expression of the enzyme in human 293T cells using a lentiviral vector, recombinant expression of GST-tagged wild-type and mutant Naa10 enzymes in Escherichia coli strain BL21
cloning of V5-tagged hNaa15p, hNaa25p, and hNaa35p from HEK-293 cell genomic DNA, expression of His-tagged and maltose binding protein-tagged subunits hNaa15p, hNaa10p, and hNaa50p in Escherichia coli, efficient expression of MBP-hNaa15p requires coexpression of pDC952, a plasmid carrying the Escherichia coli argU gene
-
gene NAA10, DNA and amino acid sequence determination and analysis, genotyping, recombinant expression of His-MBP-tagged wild-type and mutant Naa10 in Escherichia coli strain BL21 Star DE3
P41227; Q9BXJ9
gene NAA10, genotyping, recombinant expression of His-MBP-tagged wild-type and mutant Naa10 in Escherichia coli and in HeLa cells
P41227; Q9BXJ9
recombinant expression of N-terminally His-tagged NatA in Spodoptera frugiperda Sf9 cells, coexpression of tagged HYPK
P41227; Q9BXJ9
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the expression of Naa10 increases during neuronal dendritic development of cerebellar Purkinje cells
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Arnesen, T.; Gromyko, D.; Kagabo, D.; Betts, M.; Starheim, K.; Varhaug, J.; Anderson, D.; Lillehaug, J.
A novel human NatA N-terminal acetyltransferase complex: HNaa16p-hNaa10p (hNat2-hArd1)
BMC Biochem.
10
15
2009
Homo sapiens
Arnesen, T.; Starheim, K.K.; Van Damme, P.; Evjenth, R.; Dinh, H.; Betts, M.J.; Ryningen, A.; Vandekerckhove, J.; Gevaert, K.; Anderson, D.
The chaperone-like protein HYPK acts together with NatA in cotranslational N-terminal acetylation and prevention of Huntingtin aggregation
Mol. Cell. Biol.
30
1898-1909
2010
Homo sapiens
Seo, J.H.; Park, J.H.; Lee, E.J.; Kim, K.W.
Different subcellular localizations and functions of human ARD1 variants
Int. J. Oncol.
46
701-707
2015
Homo sapiens (Q6P4J0)
Magin, R.S.; March, Z.M.; Marmorstein, R.
The N-terminal acetyltransferase Naa10/ARD1 does not acetylate lysine residues
J. Biol. Chem.
291
5270-5277
2016
Homo sapiens
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)
Arnesen, T.; Thompson, P.R.; Varhaug, J.E.; Lillehaug, J.R.
The protein acetyltransferase ARD1: a novel cancer drug target?
Curr. Cancer Drug Targets
8
545-553
2008
Homo sapiens
Doerfel, M.J.; Lyon, G.J.
The biological functions of Naa10 - From amino-terminal acetylation to human disease
Gene
567
103-131
2015
Homo sapiens (P41227)
Myklebust, L.; Stove, S.; Arnesen, T.
Naa10 in development and disease
Oncotarget
6
34041-34042
2015
Homo sapiens (P41227)
McTiernan, N.; Stoeve, S.I.; Aukrust, I.; Marli, M.T.; Myklebust, L.M.; Houge, G.; Arnesen, T.
NAA10 dysfunction with normal NatA-complex activity in a girl with non-syndromic ID and a de novo NAA10 p.(V111G) variant - a case report
BMC Med. genet.
19
47
2018
Homo sapiens (P41227 AND Q9BXJ9), Homo sapiens
Ree, R.; Geithus, A.S.; Toerring, P.M.; Soerensen, K.P.; Damkjaer, M.; Damkjaer, M.; Lynch, S.A.; Arnesen, T.
A novel NAA10 p.(R83H) variant with impaired acetyltransferase activity identified in two boys with ID and microcephaly
BMC Med. Genet.
20
101
2019
Homo sapiens (P41227 AND Q9BXJ9), Homo sapiens
Chien, M.H.; Lee, W.J.; Yang, Y.C.; Tan, P.; Pan, K.F.; Liu, Y.C.; Tsai, H.C.; Hsu, C.H.; Wen, Y.C.; Hsiao, M.; Hua, K.T.
N-alpha-acetyltransferase 10 protein promotes metastasis by stabilizing matrix metalloproteinase-2 protein in human osteosarcomas
Cancer Lett.
433
86-98
2018
Homo sapiens (P41227)
Stoeve, S.I.; Blenski, M.; Stray-Pedersen, A.; Wierenga, K.J.; Jhangiani, S.N.; Akdemir, Z.C.; Crawford, D.; McTiernan, N.; Myklebust, L.M.; Purcarin, G.; McNall-Knapp, R.; Wadley, A.; Belmont, J.W.; Kim, J.J.; Lupski, J.R.; Arnesen, T.
A novel NAA10 variant with impaired acetyltransferase activity causes developmental delay, intellectual disability, and hypertrophic cardiomyopathy
Eur. J. Hum. Genet.
26
1294-1305
2018
Homo sapiens (P41227), Homo sapiens
Lee, M.N.; Kweon, H.Y.; Oh, G.T.
N-alpha-acetyltransferase 10 (NAA10) in development the role of NAA10
Exp. Mol. Med.
50
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)
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
Molecules
25
588
2020
Homo sapiens (P41227)
Deng, S.; McTiernan, N.; Wei, X.; Arnesen, T.; Marmorstein, R.
Molecular basis for N-terminal acetylation by human NatE and its modulation by HYPK
Nat. Commun.
11
818
2020
Homo sapiens (P41227 AND Q9BXJ9), Homo sapiens
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.
6
38508
2016
Homo sapiens (P41227), Mus musculus (Q9QY36), Mus musculus C57 (Q9QY36)
Lyon, G.
From molecular understanding to organismal biology of N-terminal acetyltransferases
Structure
27
1053-1055
2019
Homo sapiens (P41227 AND Q9BXJ9), Saccharomyces cerevisiae (P07347 AND P12945), Saccharomyces cerevisiae, Saccharomyces cerevisiae ATCC 204508 (P07347 AND P12945), Schizosaccharomyces pombe (Q9UTI3 AND O74985), Schizosaccharomyces pombe 972 (Q9UTI3 AND O74985), Schizosaccharomyces pombe ATCC 24843 (Q9UTI3 AND O74985)
EXTERNAL LINKS (specific for EC-Number 2.3.1.255)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
