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Information on EC 2.3.1.256 - N-terminal methionine Nalpha-acetyltransferase NatC and Organism(s) Homo sapiens and UniProt Accession Q147X3
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2.3.1.256 N-terminal methionine Nalpha-acetyltransferase NatCIUBMB 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, and may also play a role in membrane targeting and gene silencing. The NatC complex is found in all eukaryotic organisms, and specifically targets N-terminal L-methionine residues attached to bulky hydrophobic residues at the second position, including Leu, Ile, Phe, Trp, and Tyr residues.
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Word Map
- 2.3.1.256
- acetyltransferases
- dsrnas
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viruslike
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nonfermentable
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co-translationally
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non-mendelian
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
hide(3 overall reactions are displayed. Show all (5)>>)
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an N-terminal-Nalpha-acetyl-L-methionyl-L-phenylalanyl-[protein]
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Synonyms
mak10, mak3p, naa30, nat12, naa38, naa35, mak31, mak31p, hnaa30, n-terminal acetyltransferase complex c, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
MAK10
NAA30
MAK3
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MAK31
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-
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NAA30
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-
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NAA35
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NAA38
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
acetyl-CoA:N-terminal-Met-Leu/Ile/Phe/Trp/Tyr-[protein] Met 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, and may also play a role in membrane targeting and gene silencing. The NatC complex is found in all eukaryotic organisms, and specifically targets N-terminal L-methionine residues attached to bulky hydrophobic residues at the second position, including Leu, Ile, Phe, Trp, and Tyr residues.
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-L-methionyl-L-histidyl-[protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-histidyl-[protein] + CoA
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-
-
?
acetyl-CoA + an N-terminal-L-methionyl-L-isoleucyl-[protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-isoleucyl-[protein] + CoA
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-
-
?
acetyl-CoA + an N-terminal-L-methionyl-L-leucyl-[Arl8b protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-leucyl-[Arl8b protein] + CoA
high activity, the full sequence is MLALISRRWGRPVGRRRRPVRVYP
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-
?
acetyl-CoA + an N-terminal-L-methionyl-L-leucyl-[mTOR protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-leucyl-[mTOR protein] + CoA
highest activity. The full sequence is MLGTGPARWGRPVGRRRRPVRVYP
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-
?
acetyl-CoA + an N-terminal-L-methionyl-L-leucyl-[protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-leucyl-[protein] + CoA
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-
-
?
acetyl-CoA + an N-terminal-L-methionyl-L-leucyl-[RNP F protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-leucyl-[RNP F protein] + CoA
the full sequence is MLGTEGGRWGRPVGRRRRPVRVYP
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-
?
acetyl-CoA + an N-terminal-L-methionyl-L-leucyl-[RNP H protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-leucyl-[RNP H protein] + CoA
high activity, the full sequence is MLGTEGGRWGRPVGRRRRPVRVYP
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-
?
acetyl-CoA + an N-terminal-L-methionyl-L-lysyl-[protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-lysyl-[protein] + CoA
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-
-
?
acetyl-CoA + an N-terminal-L-methionyl-L-methionyl-[protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-methionyl-[protein] + CoA
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-
-
?
acetyl-CoA + an N-terminal-L-methionyl-L-phenylalanyl-[protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-phenylalanyl-[protein] + CoA
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-
-
?
acetyl-CoA + an N-terminal-L-methionyl-L-tryptophyl-[protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-tryptophyl-[protein] + CoA
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-
-
?
acetyl-CoA + an N-terminal-L-methionyl-L-tyrosinyl-[protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-tyrosinyl-[protein] + CoA
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-
-
?
acetyl-CoA + an N-terminal-L-methionyl-L-valyl-[protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-valyl-[protein] + CoA
-
-
-
?
acetyl-CoA + N-terminal-L-methionyl-L-alanyl-[PLD]
N-terminal-Nalpha-acetyl-L-methionyl-L-alanyl-[PLD] + CoA
a NatF-type substrate
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-
?
acetyl-CoA + N-terminal-L-methionyl-L-leucyl-[GPE]
N-terminal-Nalpha-acetyl-L-methionyl-L-leucyl-[GPE] + CoA
a NatE-type substrate
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-
?
acetyl-CoA + N-terminal-L-methionyl-L-leucyl-[GTG]
N-terminal-Nalpha-acetyl-L-methionyl-L-leucyl-[GTG] + CoA
a NatC-type substrate
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-
?
acetyl-CoA + N-terminal-L-methionyl-L-phenylalanyl-[Arl3 protein]
N-terminal-Nalpha-acetyl-L-methionyl-L-phenylalanyl-[Arl3 protein] + CoA
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-
-
?
additional information
?
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almost no activity with nuclear factor kappaB p65 (MDELFPLRWGRPVGRRRRPVRVYP), kinesin KIF4A (MKEEVKGRWGRPVGRRRRPVRVYP), and high-mobility group protein A1 (SESSSKSRWGRPVGRRRRPVRVYP)
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?
additional information
?
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full-length Naa30 acetylates a classical NatC substrate peptide in vitro, whereas no significant NAT activity is detected for Naa3028. Neither full-length Naa30 nor Naa30288 display any lysine acetyltransferase activity, and neither Naa30 isoforms have KAT activity towards histones. The SESSS, EEEIA and MDELF peptides are negative controls and represent NatA, Naa10 and NatB substrates, respectively. Poor activity with SGRGK peptide, which contains the natural 28-mer N-terminal sequence of histone H4, and represents a NatD-type substrate
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additional information
?
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full-length Naa30 acetylates a classical NatC substrate peptide in vitro, whereas no significant NAT activity is detected for Naa3028. Neither full-length Naa30 nor Naa30288 display any lysine acetyltransferase activity, and neither Naa30 isoforms have KAT activity towards histones. The SESSS, EEEIA and MDELF peptides are negative controls and represent NatA, Naa10 and NatB substrates, respectively. Poor activity with SGRGK peptide, which contains the natural 28-mer N-terminal sequence of histone H4, and represents a NatD-type substrate
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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-L-methionyl-L-histidyl-[protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-histidyl-[protein] + CoA
-
-
-
?
acetyl-CoA + an N-terminal-L-methionyl-L-isoleucyl-[protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-isoleucyl-[protein] + CoA
-
-
-
?
acetyl-CoA + an N-terminal-L-methionyl-L-leucyl-[Arl8b protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-leucyl-[Arl8b protein] + CoA
high activity, the full sequence is MLALISRRWGRPVGRRRRPVRVYP
-
-
?
acetyl-CoA + an N-terminal-L-methionyl-L-leucyl-[mTOR protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-leucyl-[mTOR protein] + CoA
highest activity. The full sequence is MLGTGPARWGRPVGRRRRPVRVYP
-
-
?
acetyl-CoA + an N-terminal-L-methionyl-L-leucyl-[protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-leucyl-[protein] + CoA
-
-
-
?
acetyl-CoA + an N-terminal-L-methionyl-L-leucyl-[RNP F protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-leucyl-[RNP F protein] + CoA
the full sequence is MLGTEGGRWGRPVGRRRRPVRVYP
-
-
?
acetyl-CoA + an N-terminal-L-methionyl-L-leucyl-[RNP H protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-leucyl-[RNP H protein] + CoA
high activity, the full sequence is MLGTEGGRWGRPVGRRRRPVRVYP
-
-
?
acetyl-CoA + an N-terminal-L-methionyl-L-lysyl-[protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-lysyl-[protein] + CoA
-
-
-
?
acetyl-CoA + an N-terminal-L-methionyl-L-methionyl-[protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-methionyl-[protein] + CoA
-
-
-
?
acetyl-CoA + an N-terminal-L-methionyl-L-phenylalanyl-[protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-phenylalanyl-[protein] + CoA
-
-
-
?
acetyl-CoA + an N-terminal-L-methionyl-L-tryptophyl-[protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-tryptophyl-[protein] + CoA
-
-
-
?
acetyl-CoA + an N-terminal-L-methionyl-L-tyrosinyl-[protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-tyrosinyl-[protein] + CoA
-
-
-
?
acetyl-CoA + an N-terminal-L-methionyl-L-valyl-[protein]
an N-terminal-Nalpha-acetyl-L-methionyl-L-valyl-[protein] + CoA
-
-
-
?
acetyl-CoA + N-terminal-L-methionyl-L-phenylalanyl-[Arl3 protein]
N-terminal-Nalpha-acetyl-L-methionyl-L-phenylalanyl-[Arl3 protein] + CoA
-
-
-
?
additional information
?
-
almost no activity with nuclear factor kappaB p65 (MDELFPLRWGRPVGRRRRPVRVYP), kinesin KIF4A (MKEEVKGRWGRPVGRRRRPVRVYP), and high-mobility group protein A1 (SESSSKSRWGRPVGRRRRPVRVYP)
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-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
high level of alternatively spliced nuclear isoform Naa30288
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
additional information
immunohistochemic detection in subcellular fractions
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
enzyme Naa30 belongs to the GNAT superfamily of acetyltransferases characterized by the highly conserved GNAT fold, which promotes Ac-CoA binding and substrate recognition
malfunction
physiological function
additional information
malfunction
knockdown of Naa30 induces the loss of mitochondrial membrane potential and fragmentation of mitochondria
malfunction
knockdown of Nalpha-terminal acetyltransferase complex C leads to p53-dependent apoptosis and aberrant Arf-like GTPase Arl8b localization
malfunction
depletion of the human N-terminal acetyltransferase hNaa30 disrupts Golgi integrity and Golgi-associated GTPase ADP ribosylation factor related protein 1 (ARFRP1) localization. Depletion of the hNatC catalytic subunit hNaa30 leads to disassembly of the Golgi apparatus and trans-Golgi network (TGN). ARFRP1 shifts from a predominantly cis-Golgi and TGN localization to localizing both Golgi and non-Golgi vesicular structures in hNaa30-depleted cells (smaller vesicle-like membranous compartments). Loss of membrane association of ARFRP1 is not observed. hNaa30 depletion induces Golgi scattering and induces aberrant ARFRP1 Golgi localization. Knockdown of each of the hNatC subunits in HeLa cells leads to p53-dependent apoptosis. Naa30 depletion severely disrupts mitochondrial organization. Knockdown phenotypes are specific for hNaa30 depletion and not a result of si-hNAA30-independent effects. Phenotypes, detailed overview
malfunction
overexpression of full-length Naa30 increases cell viability via inhibition of apoptosis. In contrast, Naa30288 does not exert an anti-apoptotic effect
physiological function
the enzyme is essential for mitochondrial integrity and function
physiological function
the human NatC complex (hNatC) is an evolutionarily conserved complex composed of the catalytic subunit hNaa30 (hMak3) and the auxiliary subunits hNaa35 (hMak10) and hNaa38 (hMak31). NatC Nt-acetylates Met-Leu-, Met-Ile-, Met-Phe-, Met-Trp-, Met-Val-, Met-Met-, Met-His-, and Met-Lys-N-termini. The NatC complex is one of several Nt-acetyltransferases (NATs) that perform Nt-acetylation in eukaryotes. Nt-acetylation or protein N-alpha-terminal acetylation, is the addition of an acetyl group on the Nalpha-amino group of proteins. It is one of the most abundant protein modifications in eukaryotes and displays a wide array of biological functions. The Golgi apparatus associated GTPase ADP ribosylation factor related protein 1 (ARFRP1) requires N-terminal acetylation for membrane association and based on its N-terminal sequence, it is likely to be a substrate of hNaa30. ARFRP1 is involved in endosome-to-trans-Golgi network (TGN) traffic
physiological function
the NatC complex consists of the catalytic subunit Naa30 and the auxiliary subunits Naa35 and Naa38, and can potentially Nt-acetylate cytoplasmic proteins when the initiator methionine is followed by a bulky hydrophobic/amphipathic residue at position 2. Full-length enzyme Naa30362 improves cell viability and inhibits apoptosis
additional information
homology structure modeling of Naa30 using the crystal structure of human Naa50 (PDB ID 3TFY) as template
additional information
-
homology structure modeling of Naa30 using the crystal structure of human Naa50 (PDB ID 3TFY) as template
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). NAA30_HUMAN
362
0
39320
Swiss-Prot
other Location (Reliability: 2)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
x * 84000, recombinant MBP-tagged Naa30362, SDS-PAGE, x * 75000, recombinant MBP-Naa30288, SDS-PAGE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
identification of a splice variant of human NAA30, which encodes a truncated protein named Naa30288. DNA sequencing reveals that the 900 bp product derived from alternative splicing results in a 222 bp deletion from the 3' end of exon 1 (c.550_771del). The truncated splice variant (867 bp) is otherwise identical to NAA30. Splicing NAA30_v2 translates into a truncated isoform (p.Val184_Leu257del) consisting of 288 amino acids (Naa30288). The splice variant is abundantly present in thyroid cancer tissues and in several different human cancer cell lines. Naa30288 localizes predominantly to the nucleus, as opposed to annotated Naa30 which has a cytoplasmic localization. Naa30288 is missing elements of the GNAT fold. Full-length Naa30 acetylates the classical NatC substrate peptide MLGTG in vitro, whereas no significant NAT activity is detected for Naa3028. Naa30288 appears to be enzymatically inactive. Overexpression of full-length Naa30362 increases cell viability via inhibition of apoptosis. In contrast, Naa30288 does not exert an anti-apoptotic effect
additional information
-
identification of a splice variant of human NAA30, which encodes a truncated protein named Naa30288. DNA sequencing reveals that the 900 bp product derived from alternative splicing results in a 222 bp deletion from the 3' end of exon 1 (c.550_771del). The truncated splice variant (867 bp) is otherwise identical to NAA30. Splicing NAA30_v2 translates into a truncated isoform (p.Val184_Leu257del) consisting of 288 amino acids (Naa30288). The splice variant is abundantly present in thyroid cancer tissues and in several different human cancer cell lines. Naa30288 localizes predominantly to the nucleus, as opposed to annotated Naa30 which has a cytoplasmic localization. Naa30288 is missing elements of the GNAT fold. Full-length Naa30 acetylates the classical NatC substrate peptide MLGTG in vitro, whereas no significant NAT activity is detected for Naa3028. Naa30288 appears to be enzymatically inactive. Overexpression of full-length Naa30362 increases cell viability via inhibition of apoptosis. In contrast, Naa30288 does not exert an anti-apoptotic effect
additional information
siRNA-mediated knockdown of hNAA30 gene expression in HeLa and CAL-62 cells, phenotypes, detailed overview
additional information
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siRNA-mediated knockdown of hNAA30 gene expression in HeLa and CAL-62 cells, phenotypes, detailed overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
subcellular fractionation of HeLa cells and identification of splicing variants of Naa30
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene NAA30, DNA and amino acid sequence, analysis and comparison, alternative splicing variants NAA30_v1 (Naa30362) and NAA30_v2 (Naa30288), cloning from HeLa cells, overexpression of MBP-tagged Naa30362-V5 and Naa30288-V5 in HeLa cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Starheim, K.; Gromyko, D.; Evjenth, R.; Ryningen, A.; Varhaug, J.; Lillehaug, J.; Arnesen, T.
Knockdown of human Nalpha-terminal acetyltransferase complex C leads to p53-dependent apoptosis and aberrant human Arl8b localization
Mol. Cell. Biol.
29
3569-3581
2009
Homo sapiens (Q147X3)
Van Damme, P.; Kalvik, T.V.; Starheim, K.K.; Jonckheere, V.; Myklebust, L.M.; Menschaert, G.; Varhaug, J.E.; Gevaert, K.; Arnesen, T.
A role for human N-alpha acetyltransferase 30 (Naa30) in maintaining mitochondrial integrity
Mol. Cell. Proteomics
15
3361-3372
2016
Homo sapiens (Q147X3), Homo sapiens
Osberg, C.; Aksnes, H.; Ninzima, S.; Marie, M.; Arnesen, T.
Microscopy-based Saccharomyces cerevisiae complementation model reveals functional conservation and redundancy of N-terminal acetyltransferases
Sci. Rep.
6
31627
2016
Homo sapiens (Q147X3), Homo sapiens
Starheim, K.K.; Kalvik, T.V.; Bjoerkoey, G.; Arnesen, T.
Depletion of the human N-terminal acetyltransferase hNaa30 disrupts Golgi integrity and ARFRP1 localization
Biosci. Rep.
37
BSR20170066
2017
Homo sapiens (Q147X3), Homo sapiens
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