NAA10

UniProt ID: P41227
Organism: Homo sapiens
Review Status: COMPLETE
๐Ÿ“ Provide Detailed Feedback

Gene Description

NAA10 (N-alpha-acetyltransferase 10, ARD1A) is the catalytic subunit of the NatA N-terminal acetyltransferase complex, the major co-translational N-terminal acetyltransferase in human cells. In complex with its auxiliary subunit NAA15, which anchors the enzyme to the ribosome, NAA10 transfers an acetyl group from acetyl-CoA to the free alpha-amino group of nascent polypeptide N-termini that begin with small residues (Ser, Ala, Thr, Gly, Cys, Val) exposed after initiator-methionine excision. This irreversible modification affects protein folding, stability, complex assembly, targeting and degradation. NatA activity is further modulated by the associated factors HYPK and NAA50 (the NatE catalytic subunit). NAA10 acts predominantly in the cytoplasm on ribosome-associated nascent chains, with an additional nuclear pool. The free (NAA15-unbound) form has been reported to perform internal (lysine) acetylation of selected substrates (e.g. HIF1A, HSPA1A/B, histone H4), and NAA10 has been implicated in several context-dependent regulatory roles. NAA10 is X-linked (Xq28); pathogenic variants cause Ogden syndrome and related N-terminal acetyltransferase deficiency disorders.

Existing Annotations Review

GO Term Evidence Action Reason
GO:1990189 protein N-terminal-serine acetyltransferase activity
IBA
GO_REF:0000033 		ACCEPT
Summary: Phylogenetic inference of NatA-type N-terminal serine acetylation, a core, experimentally confirmed activity of NAA10.
Reason: N-terminal Ser acetylation is a documented NatA substrate specificity directly demonstrated for human NAA10; IBA transfer is correct.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
N-terminal L-seryl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-seryl-[protein] + CoA + H(+)
GO:1990190 protein-N-terminal-glutamate acetyltransferase activity
IBA
GO_REF:0000033 		MARK AS OVER ANNOTATED
Summary: Phylogenetic inference of N-terminal glutamate acetylation. Acidic (Glu/Asp) N-termini are the specificity of NatB/NatC-type complexes, not of NatA/NAA10, whose substrates are small residues exposed after Met removal.
Reason: NAA10/NatA acetylates Ser/Ala/Thr/Gly/Cys/Val N-termini, not acidic Glu N-termini; this IBA transfer over-extends the family substrate range to a specificity not supported for NAA10.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
Acetylates amino termini that are devoid of initiator methionine
GO:0004596 protein-N-terminal amino-acid acetyltransferase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: Electronic annotation of the parent N-terminal acetyltransferase MF, consistent with NAA10's experimentally established EC 2.3.1.255 activity.
Reason: Matches the core catalytic function of NAA10 and is corroborated by direct experimental (IDA/EXP) annotations.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
Catalytic subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase activity
GO:0005634 nucleus
IEA
GO_REF:0000044 		KEEP AS NON CORE
Summary: Electronic annotation of nuclear localization, consistent with experimentally documented nuclear pool of NAA10.
Reason: Nuclear localization is documented but the core co-translational Nt-acetylation function acts on cytoplasmic ribosomes; nuclear pool is retained as non-core.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
NAA10 located_in GO:0005634 nucleus cellular_component EXP PMID:12464182
GO:0005737 cytoplasm
IEA
GO_REF:0000120 		ACCEPT
Summary: Electronic annotation of cytoplasmic localization, the principal site of NatA co-translational action.
Reason: Cytoplasm is where ribosome-associated NatA acetylates nascent chains; strongly supported by experimental annotations.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0008999 protein-N-terminal-alanine acetyltransferase activity
IEA
GO_REF:0000116 		ACCEPT
Summary: RHEA-derived electronic annotation of N-terminal alanine acetylation, a documented NatA specificity of NAA10.
Reason: N-terminal Ala acetylation is experimentally established for NAA10.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
N-terminal L-alanyl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-alanyl-[protein] + CoA + H(+)
GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups
IEA
GO_REF:0000002 		MARK AS OVER ANNOTATED
Summary: Generic acyltransferase MF from InterPro domain transfer; correct but far less informative than the specific N-terminal acetyltransferase terms.
Reason: This high-level acyltransferase term adds no information beyond the specific Nt-acetyltransferase activity; uninformative.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups molecular_function IEA
GO:0031415 NatA complex
IEA
GO_REF:0000120 		ACCEPT
Summary: Electronic annotation of NatA complex membership; NAA10 is the defining catalytic subunit of NatA.
Reason: Core complex membership, strongly supported by structural and IPI data.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15
GO:1990189 protein N-terminal-serine acetyltransferase activity
IEA
GO_REF:0000116 		ACCEPT
Summary: RHEA-derived electronic annotation duplicating the core N-terminal Ser acetylation activity.
Reason: Core activity, redundant with the EXP/IBA Ser annotations.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
N-terminal L-seryl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-seryl-[protein] + CoA + H(+)
GO:0005515 protein binding
IPI
PMID:15496142
Identification and characterization of the human ARD1-NATH p... 		KEEP AS NON CORE
Summary: IntAct interaction with NAA15 (Q9BXJ9), the auxiliary NatA subunit. The bare protein binding term is uninformative but records the functionally central NAA10-NAA15 interaction.
Reason: Records the real NAA10-NAA15 complex interaction; the informative MF (NatA complex membership / Nt-acetyltransferase activity) is captured elsewhere, so this generic term is kept non-core.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005515 protein binding molecular_function IPI PMID:15496142 UniProtKB:Q9BXJ9
GO:0005515 protein binding
IPI
PMID:16507339
Cloning and characterization of hNAT5/hSAN: an evolutionaril... 		KEEP AS NON CORE
Summary: IntAct interaction with NAA50 (Q9GZZ1), the NatE catalytic subunit that associates with NatA. Generic protein binding term.
Reason: Real NAA50 interaction underlying NatE complex formation; informative function captured by complex annotations, so kept non-core.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005515 protein binding molecular_function IPI PMID:16507339 UniProtKB:Q9GZZ1
GO:0005515 protein binding
IPI
PMID:19480662
A novel human NatA Nalpha-terminal acetyltransferase complex... 		KEEP AS NON CORE
Summary: IntAct interactions including NAA15 (Q9BXJ9), NAA50 (Q9GZZ1) and NAA16 (Q6N069), all NatA-related subunits/paralogs. Generic term.
Reason: Real interactions with NatA partners; uninformative as a bare MF, kept non-core.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005515 protein binding molecular_function IPI PMID:19480662 UniProtKB:Q6N069
GO:0005515 protein binding
IPI
PMID:21295525
N-ฮฑ-acetyltransferase 10 protein suppresses cancer cell meta... 		KEEP AS NON CORE
Summary: High-throughput interactome interactions (e.g. O55043, Q14155, Q15052). Bare protein binding term, uninformative for core function.
Reason: Real but high-throughput interactions not central to the catalytic role; kept non-core.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005515 protein binding molecular_function IPI PMID:21295525 UniProtKB:O55043
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network. 		KEEP AS NON CORE
Summary: Proteome-scale yeast two-hybrid interactome capturing many NAA10 interactions. Bare protein binding term.
Reason: High-throughput interactome data; uninformative as a core MF.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005515 protein binding molecular_function IPI PMID:25416956 UniProtKB:O43829
GO:0005515 protein binding
IPI
PMID:28514442
Architecture of the human interactome defines protein commun... 		KEEP AS NON CORE
Summary: IntAct interaction with NAA15 (Q9BXJ9). Generic protein binding term.
Reason: Records the central NAA10-NAA15 interaction; informative function captured elsewhere.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005515 protein binding molecular_function IPI PMID:28514442 UniProtKB:Q9BXJ9
GO:0005515 protein binding
IPI
PMID:31515488
Extensive disruption of protein interactions by genetic vari... 		KEEP AS NON CORE
Summary: IntAct interactions (Q13137, Q92845) from a high-throughput study. Bare protein binding term.
Reason: High-throughput interactions; uninformative as a core MF.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005515 protein binding molecular_function IPI PMID:31515488 UniProtKB:Q13137
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome. 		KEEP AS NON CORE
Summary: Large high-throughput interactome screen capturing numerous NAA10 interactions. Bare protein binding term.
Reason: High-throughput interactome data; uninformative as core MF.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005515 protein binding molecular_function IPI PMID:32296183 UniProtKB:O43829
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ... 		KEEP AS NON CORE
Summary: Neurodegeneration interactome screen capturing interactions (e.g. APP P05067, RAC1 P63000). Bare protein binding term.
Reason: High-throughput interactions not central to the catalytic function.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005515 protein binding molecular_function IPI PMID:32814053 UniProtKB:P05067
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling... 		KEEP AS NON CORE
Summary: BioPlex affinity-purification interactome capturing NatA-related partners (NAA15 Q9BXJ9, NAA50 Q9GZZ1, NAA16 Q6N069). Bare protein binding term.
Reason: Records real NatA-partner interactions; informative function captured by complex annotations.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005515 protein binding molecular_function IPI PMID:33961781 UniProtKB:Q9BXJ9
GO:0005515 protein binding
IPI
PMID:35156780
CFTR interactome mapping using the mammalian membrane two-hy... 		KEEP AS NON CORE
Summary: IntAct interaction with HTT (P13569, huntingtin). Bare protein binding term.
Reason: High-throughput interaction; uninformative as core MF.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005515 protein binding molecular_function IPI PMID:35156780 UniProtKB:P13569
GO:0005515 protein binding
IPI
PMID:36012204
Differential CFTR-Interactome Proximity Labeling Procedures ... 		KEEP AS NON CORE
Summary: IntAct interaction with HTT (P13569, huntingtin). Bare protein binding term.
Reason: High-throughput interaction; uninformative as core MF.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005515 protein binding molecular_function IPI PMID:36012204 UniProtKB:P13569
GO:0005515 protein binding
IPI
PMID:36442525
ARD1 stabilizes NRF2 through direct interaction and promotes... 		KEEP AS NON CORE
Summary: IntAct interaction with a high-throughput partner (Q16236). Bare protein binding term.
Reason: High-throughput interaction; uninformative as core MF.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005515 protein binding molecular_function IPI PMID:36442525 UniProtKB:Q16236
GO:0005515 protein binding
IPI
PMID:40205054
Multimodal cell maps as a foundation for structural and func... 		KEEP AS NON CORE
Summary: Multimodal cell-maps interactome capturing NatA-related partners (NAA15 Q9BXJ9, NAA50 Q9GZZ1, NAA16 Q6N069). Bare protein binding term.
Reason: Records real NatA-partner interactions; informative function captured elsewhere.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005515 protein binding molecular_function IPI PMID:40205054 UniProtKB:Q9BXJ9
GO:0008080 N-acetyltransferase activity
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: Generic N-acetyltransferase MF from ortholog transfer; correct but less specific than the N-terminal acetyltransferase terms.
Reason: Higher-level than the specific Nt-acetyltransferase activity; adds no information beyond the precise terms.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0008080 N-acetyltransferase activity molecular_function IEA GO_REF:0000107
GO:0005829 cytosol
IDA
GO_REF:0000052 		ACCEPT
Summary: Direct immunofluorescence (HPA) cytosolic localization, consistent with ribosome-associated NatA function in the cytoplasm.
Reason: Cytosol is the principal site of co-translational Nt-acetylation.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005829 cytosol cellular_component IDA GO_REF:0000052 HPA
GO:0005634 nucleus
EXP
PMID:12464182
Regulation and destabilization of HIF-1alpha by ARD1-mediate... 		KEEP AS NON CORE
Summary: Experimental nuclear localization of NAA10, where a free pool acts on substrates such as HIF1A.
Reason: Documented nuclear pool; non-core relative to cytoplasmic co-translational NatA function.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005634 nucleus cellular_component EXP PMID:12464182
GO:0005737 cytoplasm
EXP
PMID:12464182
Regulation and destabilization of HIF-1alpha by ARD1-mediate... 		ACCEPT
Summary: Experimental cytoplasmic localization, the principal site of NatA action.
Reason: Core localization for co-translational Nt-acetylation.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005737 cytoplasm cellular_component EXP PMID:12464182
GO:0008999 protein-N-terminal-alanine acetyltransferase activity
EXP
PMID:15496142
Identification and characterization of the human ARD1-NATH p... 		ACCEPT
Summary: Experimental demonstration of N-terminal alanine acetylation by NatA, a core specificity of NAA10.
Reason: Direct experimental evidence for a core NatA substrate specificity.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
N-terminal L-alanyl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-alanyl-[protein] + CoA + H(+)
GO:0008999 protein-N-terminal-alanine acetyltransferase activity
EXP
PMID:19420222
Proteomics analyses reveal the evolutionary conservation and... 		ACCEPT
Summary: Experimental N-terminal alanine acetylation (acetylation of termini devoid of initiator Met), a core NatA activity.
Reason: Direct experimental evidence for core NatA specificity.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
Acetylates amino termini that are devoid of initiator methionine
GO:0008999 protein-N-terminal-alanine acetyltransferase activity
EXP
PMID:25489052
Biochemical and cellular analysis of Ogden syndrome reveals ... 		ACCEPT
Summary: Experimental N-terminal alanine acetylation by NatA, core specificity.
Reason: Direct experimental evidence for core NatA specificity.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
N-terminal L-alanyl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-alanyl-[protein] + CoA + H(+)
GO:1990189 protein N-terminal-serine acetyltransferase activity
EXP
PMID:15496142
Identification and characterization of the human ARD1-NATH p... 		ACCEPT
Summary: Experimental N-terminal serine acetylation, a core NatA specificity of NAA10.
Reason: Direct experimental evidence; this is the prototypical NatA substrate.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
N-terminal L-seryl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-seryl-[protein] + CoA + H(+)
GO:1990189 protein N-terminal-serine acetyltransferase activity
EXP
PMID:19420222
Proteomics analyses reveal the evolutionary conservation and... 		ACCEPT
Summary: Experimental N-terminal serine acetylation by NatA.
Reason: Direct experimental evidence for core specificity.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
N-terminal L-seryl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-seryl-[protein] + CoA + H(+)
GO:1990189 protein N-terminal-serine acetyltransferase activity
EXP
PMID:25489052
Biochemical and cellular analysis of Ogden syndrome reveals ... 		ACCEPT
Summary: Experimental N-terminal serine acetylation by NatA.
Reason: Direct experimental evidence for core specificity.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
N-terminal L-seryl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-seryl-[protein] + CoA + H(+)
GO:1990189 protein N-terminal-serine acetyltransferase activity
EXP
PMID:29754825
Structure of Human NatA and Its Regulation by the Huntingtin... 		ACCEPT
Summary: Experimental N-terminal serine acetylation by NatA, from structural/ kinetic characterization of the human NatA/NatE complex.
Reason: Direct experimental evidence for core specificity.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
N-terminal L-seryl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-seryl-[protein] + CoA + H(+)
GO:0051604 protein maturation
IDA
PMID:15496142
Identification and characterization of the human ARD1-NATH p... 		KEEP AS NON CORE
Summary: N-terminal acetylation is part of co-translational protein maturation; a plausible biological-process outcome of NatA activity.
Reason: Maturation is a broad downstream process of Nt-acetylation; the core is the catalytic MF. Retained as non-core BP.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
Catalytic subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase activity
GO:0051604 protein maturation
IDA
PMID:19480662
A novel human NatA Nalpha-terminal acetyltransferase complex... 		KEEP AS NON CORE
Summary: N-terminal acetylation as part of protein maturation; broad BP outcome of NatA activity.
Reason: Downstream process of the catalytic MF; kept non-core.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
Catalytic subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase activity
GO:1904592 positive regulation of protein refolding
IDA
PMID:27708256
ARD1-mediated Hsp70 acetylation balances stress-induced prot... 		KEEP AS NON CORE
Summary: NAA10 (ARD1) acetylates Hsp70 (HSPA1A/B at Lys-77), enhancing chaperone activity and balancing stress-induced protein refolding versus degradation. This is a context-dependent moonlighting (internal lysine acetylation) role, distinct from co-translational Nt-acetylation.
Reason: Supported by direct experimental evidence but represents a specialized moonlighting (lysine-acetylation) function, not the core Nt-acetyltransferase activity.
Supporting Evidence:
PMID:27708256
ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding and degradation
GO:0005737 cytoplasm
IDA
PMID:15496142
Identification and characterization of the human ARD1-NATH p... 		ACCEPT
Summary: Direct cytoplasmic localization (ComplexPortal NatA), the principal site of co-translational acetylation.
Reason: Core localization for NatA function.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005737 cytoplasm cellular_component IDA PMID:15496142 Homo sapiens ComplexPortal
GO:0031415 NatA complex
IPI
PMID:15496142
Identification and characterization of the human ARD1-NATH p... 		ACCEPT
Summary: Direct evidence that NAA10 is part of the NatA complex (with NAA15).
Reason: Core complex membership, directly demonstrated.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15
GO:0031415 NatA complex
IPI
PMID:19480662
A novel human NatA Nalpha-terminal acetyltransferase complex... 		ACCEPT
Summary: Direct evidence for NatA complex membership.
Reason: Core complex membership, directly demonstrated.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15
GO:0004596 protein-N-terminal amino-acid acetyltransferase activity
IDA
PMID:25489052
Biochemical and cellular analysis of Ogden syndrome reveals ... 		ACCEPT
Summary: Direct experimental evidence for N-terminal amino-acid acetyltransferase activity, the core catalytic function.
Reason: Core catalytic MF, directly demonstrated.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
Catalytic subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase activity
GO:0005515 protein binding
IPI
PMID:25489052
Biochemical and cellular analysis of Ogden syndrome reveals ... 		KEEP AS NON CORE
Summary: IntAct interactions with NAA15 (Q9BXJ9) and NAA50 (Q9GZZ1), NatA/NatE subunits. Generic protein binding term.
Reason: Records central NatA/NatE subunit interactions; informative function captured elsewhere.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005515 protein binding molecular_function IPI PMID:25489052 UniProtKB:Q9BXJ9
GO:0005737 cytoplasm
IDA
PMID:25489052
Biochemical and cellular analysis of Ogden syndrome reveals ... 		ACCEPT
Summary: Direct cytoplasmic localization of NAA10.
Reason: Core localization for NatA function.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005737 cytoplasm cellular_component IDA PMID:25489052
GO:2000719 negative regulation of maintenance of mitotic sister chromatid cohesion, centromeric
IDA
PMID:27422821
Opposing Functions of the N-terminal Acetyltransferases Naa5... 		KEEP AS NON CORE
Summary: NAA10 reported as a negative regulator of sister chromatid cohesion during mitosis; a specialized context-dependent role.
Reason: Documented experimentally but a specialized non-core function distinct from co-translational Nt-acetylation.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
Acts as a negative regulator of sister chromatid cohesion during mitosis
GO:0005515 protein binding
IPI
PMID:27708256
ARD1-mediated Hsp70 acetylation balances stress-induced prot... 		KEEP AS NON CORE
Summary: IntAct interaction with HSPA1A/HSPA1B (P0DMV8/P0DMV9), the Hsp70 substrate acetylated by NAA10. Generic protein binding term.
Reason: Real interaction underlying the moonlighting Hsp70-acetylation role; uninformative as a bare MF.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005515 protein binding molecular_function IPI PMID:27708256 UniProtKB:P0DMV8
GO:0005634 nucleus
IDA
PMID:25732826
An organellar Nฮฑ-acetyltransferase, Naa60, acetylates cytoso... 		KEEP AS NON CORE
Summary: Direct nuclear localization of NAA10.
Reason: Documented nuclear pool; non-core relative to cytoplasmic NatA function.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005634 nucleus cellular_component IDA PMID:25732826
GO:0005737 cytoplasm
IDA
PMID:25732826
An organellar Nฮฑ-acetyltransferase, Naa60, acetylates cytoso... 		ACCEPT
Summary: Direct cytoplasmic localization of NAA10.
Reason: Core localization for NatA function.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005737 cytoplasm cellular_component IDA PMID:25732826
GO:0016020 membrane
HDA
PMID:19946888
Defining the membrane proteome of NK cells. 		MARK AS OVER ANNOTATED
Summary: Membrane localization from a high-throughput membrane proteome dataset; not consistent with NAA10's soluble cytoplasmic/ribosome-associated function.
Reason: HDA membrane proteome hit; likely reflects co-purification rather than a genuine integral-membrane localization for this soluble enzyme.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0016020 membrane cellular_component HDA PMID:19946888
GO:0004596 protein-N-terminal amino-acid acetyltransferase activity
IDA
PMID:19480662
A novel human NatA Nalpha-terminal acetyltransferase complex... 		ACCEPT
Summary: Direct evidence that NAA10 contributes the catalytic N-terminal acetyltransferase activity to the NatA complex.
Reason: Core catalytic MF; the contributes_to qualifier correctly reflects that catalysis occurs in the NAA10-NAA15 complex.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
Catalytic subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase activity
GO:0031415 NatA complex
IDA
PMID:19480662
A novel human NatA Nalpha-terminal acetyltransferase complex... 		ACCEPT
Summary: Direct evidence for NatA complex membership.
Reason: Core complex membership.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15
GO:0043022 ribosome binding
IDA
PMID:19480662
A novel human NatA Nalpha-terminal acetyltransferase complex... 		ACCEPT
Summary: NAA10/NatA binds the ribosome, enabling co-translational acetylation of nascent chains. Ribosome anchoring is largely conferred by NAA15.
Reason: Ribosome binding is a documented and functionally important MF for the co-translational action of NatA.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
Interacts with the ribosome
GO:0005634 nucleus
IDA
PMID:15496142
Identification and characterization of the human ARD1-NATH p... 		KEEP AS NON CORE
Summary: Direct nuclear localization of NAA10.
Reason: Documented nuclear pool; non-core relative to cytoplasmic NatA function.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005634 nucleus cellular_component IDA PMID:15496142
GO:0016407 acetyltransferase activity
IDA
PMID:15496142
Identification and characterization of the human ARD1-NATH p... 		MARK AS OVER ANNOTATED
Summary: Generic acetyltransferase MF; correct but less informative than the specific N-terminal acetyltransferase terms.
Reason: High-level term superseded by the specific Nt-acetyltransferase annotations.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0016407 acetyltransferase activity molecular_function IDA PMID:15496142
GO:0043022 ribosome binding
IDA
PMID:15496142
Identification and characterization of the human ARD1-NATH p... 		ACCEPT
Summary: NAA10/NatA binds the ribosome, enabling co-translational Nt-acetylation.
Reason: Functionally important MF for co-translational action of NatA.
Supporting Evidence:
file:human/NAA10/NAA10-uniprot.txt
Interacts with the ribosome
GO:0005634 nucleus
TAS
PMID:7981673
Isolation of new genes in distal Xq28: transcriptional map a... 		KEEP AS NON CORE
Summary: Early traceable-author statement placing the protein in the nucleus.
Reason: Consistent with the documented nuclear pool; non-core relative to cytoplasmic NatA function.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0005634 nucleus cellular_component TAS PMID:7981673
GO:0008080 N-acetyltransferase activity
TAS
PMID:7981673
Isolation of new genes in distal Xq28: transcriptional map a... 		MARK AS OVER ANNOTATED
Summary: Early traceable-author statement of N-acetyltransferase activity; generic relative to the specific Nt-acetyltransferase terms.
Reason: Generic term superseded by specific Nt-acetyltransferase annotations.
Supporting Evidence:
file:human/NAA10/NAA10-goa.tsv
GO:0008080 N-acetyltransferase activity molecular_function TAS PMID:7981673

Core Functions

Catalytic subunit of the NatA complex catalyzing co-translational N-terminal (alpha-amino) acetylation of nascent polypeptides bearing small N-terminal residues (Ser, Ala, Thr, Gly, Cys, Val) exposed after initiator-methionine excision, using acetyl-CoA (EC 2.3.1.255).

Molecular Function:
protein-N-terminal amino-acid acetyltransferase activity
Cellular Locations:
cytoplasm
Supporting Evidence:
  • file:human/NAA10/NAA10-uniprot.txt
    Catalytic subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase activity
  • file:human/NAA10/NAA10-uniprot.txt
    Acetylates amino termini that are devoid of initiator methionine

As the catalytic component of the ribosome-associated NatA complex, NAA10 partners with the auxiliary subunit NAA15 (which anchors the enzyme to the ribosome) to act co-translationally on emerging nascent chains.

Molecular Function:
ribosome binding
In Complex:
NatA complex
Supporting Evidence:
  • file:human/NAA10/NAA10-uniprot.txt
    Interacts with the ribosome
  • file:human/NAA10/NAA10-uniprot.txt
    Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB Subcellular Location vocabulary mapping
GO_REF:0000052
Gene Ontology annotation based on curation of immunofluorescence data
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
GO_REF:0000116
Gene Ontology annotation based on rules generated from manual annotation (RHEA)
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:12464182
Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation.
  • NAA10 (ARD1) localizes to both cytoplasm and nucleus; the free form can perform internal acetylation of substrates such as HIF1A.
PMID:15496142
Identification and characterization of the human ARD1-NATH protein acetyltransferase complex.
  • Human NatA (ARD1/NAA10 + NATH/NAA15) is a ribosome-associated complex with N-terminal acetyltransferase activity for Ser/Ala N-termini.
PMID:16507339
Cloning and characterization of hNAT5/hSAN: an evolutionarily conserved component of the NatA protein N-alpha-acetyltransferase complex.
  • NAA50 associates with the NatA (NAA10-NAA15) complex.
PMID:19420222
Proteomics analyses reveal the evolutionary conservation and divergence of N-terminal acetyltransferases from yeast and humans.
  • NatA/NAA10 acetylates N-termini exposed after initiator methionine removal (Ser, Ala, Thr, Gly, Cys, Val).
PMID:19480662
A novel human NatA Nalpha-terminal acetyltransferase complex: hNaa16p-hNaa10p (hNat2-hArd1).
  • NAA10 is the catalytic subunit of the ribosome-associated NatA complex and contributes its N-terminal acetyltransferase activity.
PMID:19946888
Defining the membrane proteome of NK cells.
PMID:21295525
N-ฮฑ-acetyltransferase 10 protein suppresses cancer cell metastasis by binding PIX proteins and inhibiting Cdc42/Rac1 activity.
PMID:25416956
A proteome-scale map of the human interactome network.
PMID:25489052
Biochemical and cellular analysis of Ogden syndrome reveals downstream Nt-acetylation defects.
  • Crystal structure and biochemistry of the NatA (NAA10-NAA15) complex explaining its N-terminal acetyltransferase activity and specificity.
PMID:25732826
An organellar Nฮฑ-acetyltransferase, Naa60, acetylates cytosolic N termini of transmembrane proteins and maintains Golgi integrity.
  • NAA10 shows nuclear and cytoplasmic localization.
PMID:27422821
Opposing Functions of the N-terminal Acetyltransferases Naa50 and NatA in Sister-chromatid Cohesion.
  • NAA10 acts as a negative regulator of centromeric sister chromatid cohesion in mitosis.
PMID:27708256
ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding and degradation.
  • NAA10/ARD1 acetylates Hsp70 (HSPA1A/B), modulating the balance between stress-induced protein refolding and degradation.
PMID:28514442
Architecture of the human interactome defines protein communities and disease networks.
PMID:29754825
Structure of Human NatA and Its Regulation by the Huntingtin Interacting Protein HYPK.
  • Structural/kinetic characterization of the human NatA/NatE complex and its modulation by HYPK, confirming N-terminal Ser acetylation.
PMID:31515488
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
PMID:32296183
A reference map of the human binary protein interactome.
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
PMID:35156780
CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system.
PMID:36012204
Differential CFTR-Interactome Proximity Labeling Procedures Identify Enrichment in Multiple SLC Transporters.
PMID:36442525
ARD1 stabilizes NRF2 through direct interaction and promotes colon cancer progression.
PMID:40205054
Multimodal cell maps as a foundation for structural and functional genomics.
PMID:7981673
Isolation of new genes in distal Xq28: transcriptional map and identification of a human homologue of the ARD1 N-acetyl transferase of Saccharomyces cerevisiae.

Suggested Questions for Experts

Q: To what extent is the internal (lysine) acetyltransferase activity of free NAA10 a genuine physiological function versus an in vitro property of the NAA15-unbound enzyme?

Q: How do Ogden syndrome variants (e.g. Ser37Pro) differentially impair NatA catalysis, NAA15 binding, and ribosome association?

Suggested Experiments

Experiment: N-terminal acetylome (N-terminal COFRADIC / SILAC) profiling in NAA10 patient-variant versus wild-type cells to quantify substrate-specific loss of Nt-acetylation.

Experiment: Reconstitution of NatA with and without NAA15/HYPK/NAA50 to dissect how each auxiliary factor modulates NAA10 catalytic specificity and ribosome binding.

Experiment: Targeted proteomics to test whether reported lysine-acetylation substrates (HIF1A, HSPA1A, TSC2) are modified by free NAA10 in vivo under physiological conditions.

๐Ÿ“š Additional Documentation

Notes

(NAA10-notes.md)

NAA10 (ARD1A) research notes

UniProt P41227, NAA10_HUMAN, 235 aa. X-linked (Xq28).

Core identity

NAA10 is the catalytic subunit of the NatA N-terminal acetyltransferase complex.
- UniProt: "RecName: N-alpha-acetyltransferase 10"; "AltName: NatA catalytic subunit Naa10"; EC=2.3.1.255.
- "Catalytic subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase activity" [P41227 FUNCTION].
- "Acetylates amino termini that are devoid of initiator methionine" [PubMed:19420222] โ€” i.e. co-translational Nt-acetylation of Ser/Ala/Thr/Gly/Cys/Val N-termini exposed after Met excision.
- Belongs to the "acetyltransferase family. ARD1 subfamily."

Complex membership

  • NatA = NAA10 + NAA15 (auxiliary/anchoring subunit). NAA15 confers N-terminal specificity and ribosome anchoring; free NAA10 (without NAA15) has different/internal-acetylation activity.
  • NatA/HYPK complex = NAA10 + NAA15 + HYPK (HYPK modulates activity).
  • NatE complex = NAA10 + NAA15 + NAA50.
  • Structures: NatA crystal/EM with NAA15 and HYPK [PubMed:29754825; PubMed:32042062].

Catalytic activities (RHEA, all EC 2.3.1.255), from UniProt CATALYTIC ACTIVITY

  • N-terminal Gly, Ala, Ser, Val, Cys, Thr acetylation. Evidence PubMed:15496142, 19420222, 25489052, 29754825.

Moonlighting / debated lysine-acetyltransferase roles

  • Without NAA15, "displays epsilon (internal) acetyltransferase activity towards HIF1A, thereby promoting its degradation" [PubMed:12464182].
  • "Represses MYLK kinase activity by acetylation" [PubMed:19826488].
  • "Acetylates, and stabilizes TSC2, thereby repressing mTOR activity" [PubMed:20145209].
  • "Acetylates HSPA1A and HSPA1B at 'Lys-77' which enhances its chaperone activity and leads to preferential binding to co-chaperone HOPX" [PubMed:27708256] โ€” basis of GO:1904592 positive regulation of protein refolding.
  • "Acetylates HIST1H4A" [PubMed:29754825].
  • "Acts as a negative regulator of sister chromatid cohesion during mitosis" [PubMed:27422821] โ€” basis of GO:2000719.
    These are real but secondary/context-dependent moonlighting functions; the CORE is co-translational Nt-acetylation. Per batch instructions keep Nt-acetyltransferase as core.

Localization

  • Cytoplasm (also free cytosolic and cytoskeleton-bound polysomes) and Nucleus [PubMed:12464182, 15496142, 25489052, 25732826].
  • Membrane HDA (PMID:19946888) = large-scale membrane proteome; non-core.

Disease

  • Ogden syndrome / N-terminal acetyltransferase deficiency (NATD, MIM:300855); X-linked, S37P (Ser-37โ†’Pro) and other variants impair Nt-acetylation.
  • MCOPS1 (Lenz microphthalmia, MIM:309800).

Interactome (IPI protein binding)

Many IntAct HT interactions; key biologically-meaningful partners: NAA15 (Q9BXJ9), NAA50 (Q9GZZ1), NAA16 (Q6N069), HIF1A, HSPA1A/B (P0DMV8/P0DMV9). The bulk of GO:0005515 IPI annotations are HT screens; keep as non-core (real interactions but uninformative term).

GOA notable

  • GO:1990189 protein N-terminal-serine acetyltransferase activity (EXP/IBA) โ€” CORE.
  • GO:1990190 protein-N-terminal-glutamate acetyltransferase activity (IBA) โ€” Glu/Asp acetylation is the NatB/NatC-type specificity; for NAA10 this is a phylogenetic over-transfer (NatA does Ser/Ala/Thr/Gly/Cys/Val, NOT acidic Glu/Asp). Mark as over-annotated.
  • GO:0008999 protein-N-terminal-alanine acetyltransferase activity (EXP) โ€” CORE.
  • GO:0004596 protein-N-terminal amino-acid acetyltransferase activity (IDA) โ€” CORE (parent MF).
  • GO:0043022 ribosome binding (IDA, contributes_to) โ€” real, supports co-translational action; accept (informative MF).
  • GO:0031415 NatA complex (part_of) โ€” accept core complex.

Pn Notes

(NAA10-pn-notes.md)

NAA10 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: P41227
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-batch-2026-06-07c
  • Batch change status: added

Source Files Checked

Deep Research Files

  • No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

  • Description: NAA10 (N-alpha-acetyltransferase 10, ARD1A) is the catalytic subunit of the NatA N-terminal acetyltransferase complex, the major co-translational N-terminal acetyltransferase in human cells. In complex with its auxiliary subunit NAA15, which anchors the enzyme to the ribosome, NAA10 transfers an acetyl group from acetyl-CoA to the free alpha-amino group of nascent polypeptide N-termini that begin with small residues (Ser, Ala, Thr, Gly, Cys, Val) exposed after initiator-methionine excision. This irreversible modification affects protein folding, stability, complex assembly, targeting and degradation. NatA activity is further modulated by the associated factors HYPK and NAA50 (the NatE catalytic subunit). NAA10 acts predominantly in the cytoplasm on ribosome-associated nascent chains, with an additional nuclear pool. The free (NAA15-unbound) form has been reported to perform internal (lysine) acetylation of selected substrates (e.g. HIF1A, HSPA1A/B, histone H4), and NAA10 has been implicated in several context-dependent regulatory roles. NAA10 is X-linked (Xq28); pathogenic variants cause Ogden syndrome and related N-terminal acetyltransferase deficiency disorders.
  • Existing/core annotation action counts: ACCEPT: 25; KEEP_AS_NON_CORE: 25; MARK_AS_OVER_ANNOTATED: 6

PN Consistency Summary

  • Consistency: Excellent agreement for the core. Review (catalytic NatA subunit), notes, and PN all agree NAA10 is the catalytic NatA subunit: NatA complex (GO:0031415, IDA/IPI accepted) and N-terminal acetyltransferase activity (GO:0004596/GO:1990189/GO:0008999, EXP/IDA accepted). The ALP/mTORC1-via-TSC2 role is a documented moonlighting function; the PN correctly maps it to nothing (no_mapping), and the review treats the analogous moonlighting (Hsp70 acetylation GO:1904592, sister-chromatid GO:2000719) as KEEP_AS_NON_CORE. No contradictions.
  • PN story / NEW pressure: The Nt-acetylation BP GO:0006474 is flagged more_specific_than_existing_goa (new_to_goa for that exact term) but is the parent of NAA10's existing specific EXP terms (GO:1990189 Ser, GO:0008999 Ala) โ€” so it is already captured at finer granularity; adding the generic parent adds nothing. No genuine NEW pressure. The TSC2/mTOR/autophagy story (PN ALP row) is real but moonlighting and correctly left unmapped; not a defensible universal GO assertion.
  • Evidence alignment: PN ALP row cites the ARD1/TSC2/mTOR Science Signaling paper (Kim et al.); the review does not cite that specific paper but captures equivalent moonlighting via PMID:27708256 (Hsp70) and PMID:27422821 (cohesion). PN TR row carries no titles. Core NatA evidence (PMID:15496142, 19480662, 25489052, 29754825) is robust and VERIFIED. Note: review flags PMID:25732826 as WRONG_IDENTIFIER (resolves to a Naa60 paper) โ€” a citation issue already adjudicated, unrelated to PN.
  • Verdict: Consistent; catalytic-subunit role correct; moonlighting correctly non-core/unmapped. No edits. (The PN GO:0006474 projection is redundant given NAA10's specific Ser/Ala EXP terms.)

Full Consistency Review

  • UniProt: P41227 ยท batch: proteostasis-batch-2026-06-07c ยท review status: COMPLETE
  • PN placement: two rows โ€” Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide|NatA/NatE complex component (TR) and Autophagy-Lysosome Pathway|Pre-initiation autophagy signaling|mTORC1 pathway, upstream|mTORC1 signal integration (ALP). PN-node mapping: NatA/NatE subtypeโ†’GO:0031415 NatA complex (mapped, CC); Nt-acetylation typeโ†’GO:0006474 N-terminal protein amino acid acetylation (mapped, BP); ALP nodes all no_mapping/context_only.
  • Consistency: Excellent agreement for the core. Review (catalytic NatA subunit), notes, and PN all agree NAA10 is the catalytic NatA subunit: NatA complex (GO:0031415, IDA/IPI accepted) and N-terminal acetyltransferase activity (GO:0004596/GO:1990189/GO:0008999, EXP/IDA accepted). The ALP/mTORC1-via-TSC2 role is a documented moonlighting function; the PN correctly maps it to nothing (no_mapping), and the review treats the analogous moonlighting (Hsp70 acetylation GO:1904592, sister-chromatid GO:2000719) as KEEP_AS_NON_CORE. No contradictions.
  • PN story / NEW pressure: The Nt-acetylation BP GO:0006474 is flagged more_specific_than_existing_goa (new_to_goa for that exact term) but is the parent of NAA10's existing specific EXP terms (GO:1990189 Ser, GO:0008999 Ala) โ€” so it is already captured at finer granularity; adding the generic parent adds nothing. No genuine NEW pressure. The TSC2/mTOR/autophagy story (PN ALP row) is real but moonlighting and correctly left unmapped; not a defensible universal GO assertion.
  • Mapping strategy: No node change needed. GO:0031415 NatA complex is exact for NAA10. GO:0006474 projection is a broader parent of the gene's specific MF terms โ€” acceptable as a node-level label but redundant at gene level. NAA10 is the right anchor (catalytic subunit) for the NatA node.
  • Evidence alignment: PN ALP row cites the ARD1/TSC2/mTOR Science Signaling paper (Kim et al.); the review does not cite that specific paper but captures equivalent moonlighting via PMID:27708256 (Hsp70) and PMID:27422821 (cohesion). PN TR row carries no titles. Core NatA evidence (PMID:15496142, 19480662, 25489052, 29754825) is robust and VERIFIED. Note: review flags PMID:25732826 as WRONG_IDENTIFIER (resolves to a Naa60 paper) โ€” a citation issue already adjudicated, unrelated to PN.
  • Verdict: Consistent; catalytic-subunit role correct; moonlighting correctly non-core/unmapped. No edits. (The PN GO:0006474 projection is redundant given NAA10's specific Ser/Ala EXP terms.)

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07c
  • review_yaml: genes/human/NAA10/NAA10-ai-review.yaml
  • PN workbook rows: 2

PN row 1: Translation | Cytosolic translation | Nascent peptide husbandry | N-terminal acetylation of nascent peptide | NatA/NatE complex component

  • UniProt: P41227
  • In branches: TR, ALP
  • PN-node mapping records (path + ancestors):
    • [subtype] Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide|NatA/NatE complex component
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0031415 NatA complex]
      rationale: This subtype is an exact cellular-component match: members are subunits of the NatA N-terminal acetyltransferase complex. The parent maps the BP (GO:0006474 N-terminal protein amino acid acetylation); this node adds the complementary, non-redundant complex-membership CC term.
    • [type] Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0006474 N-terminal protein amino acid acetylation]
      rationale: This PN type denotes N-terminal acetyltransferase machinery acting on nascent peptides. The GO N-terminal acetylation process is the direct target.
    • [group] Translation|Cytosolic translation|Nascent peptide husbandry
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a broad PN category rather than a single GO class. The member genes span multiple activities, complexes, or contexts, so direct propagation from this node would overstate the shared biology.
    • [class] Translation|Cytosolic translation
      status=context_only scope=too_broad_to_propagate GO=[GO:0002181 cytoplasmic translation]
      rationale: The PN class Cytosolic translation is centered on the cytoplasmic translation apparatus and process, but it also houses supporting machinery such as ribosome biogenesis factors. The GO process term is a useful high-level label for the class, but propagating it to all members would over-annotate genes whose PN placement is through assembly or maturation context rather than core cytoplasmic translation.
    • [branch] Translation
      status=context_only scope=too_broad_to_propagate GO=[GO:0006412 translation]
      rationale: The PN Translation branch is organized around the translation apparatus and immediately associated cotranslational quality-control systems. GO translation is the closest high-level process label, but the PN branch also contains adjacent machinery such as ribosome biogenesis and nascent-chain handling. Keeping this relationship is useful for interpretation, but it is too broad to project safely onto every member.

PN row 2: Autophagy-Lysosome Pathway | Pre-initiation autophagy signaling | mTORC1 pathway, upstream | mTORC1 signal integration

  • UniProt: P41227
  • In branches: TR, ALP
  • Notes: aka ARD1. Arrest-defective protein 1 (ARD1) physically interacts with, acetylates, and stabilizes TSC2, thereby repressing mTOR activity. The inhibition of mTOR by ARD1 inhibits cell proliferation and increases autophagy, thereby inhibiting tumorigenicity.
  • PN references (titles):
    • ARD1 Stabilization of TSC2 Suppresses Tumorigenesis Through the mTOR Signaling Pathway | Science Signaling (sciencemag.org)
  • PN-node mapping records (path + ancestors):
    • [type] Autophagy-Lysosome Pathway|Pre-initiation autophagy signaling|mTORC1 pathway, upstream|mTORC1 signal integration
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a contextual PN role. The label is useful for curator triage, but by itself does not support a universal GO assertion for all member genes beyond curated ancestor or child mappings.
    • [group] Autophagy-Lysosome Pathway|Pre-initiation autophagy signaling|mTORC1 pathway, upstream
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
    • [class] Autophagy-Lysosome Pathway|Pre-initiation autophagy signaling
      status=context_only scope=too_broad_to_propagate GO=[GO:0010506 regulation of autophagy]
      rationale: This class organizes upstream signaling inputs to autophagy initiation. Because the subtree contains generic insulin, AMPK, mTORC1, nutrient-sensing, and miscellaneous signaling components, class-level propagation to regulation of autophagy would over-annotate many genes.
    • [branch] Autophagy-Lysosome Pathway
      status=no_mapping scope= GO=[]
      rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

Projected GO annotations (1)

  • GO:0006474 N-terminal protein amino acid acetylation | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

๐Ÿ“„ View Raw YAML

 
id: P41227
gene_symbol: NAA10
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: NAA10 (N-alpha-acetyltransferase 10, ARD1A) is the catalytic subunit of the NatA N-terminal acetyltransferase complex, the major co-translational N-terminal acetyltransferase in human cells. In complex with its auxiliary subunit NAA15, which anchors the enzyme to the ribosome, NAA10 transfers an acetyl group from acetyl-CoA to the free alpha-amino group of nascent polypeptide N-termini that begin with small residues (Ser, Ala, Thr, Gly, Cys, Val) exposed after initiator-methionine excision. This irreversible modification affects protein folding, stability, complex assembly, targeting and degradation. NatA activity is further modulated by the associated factors HYPK and NAA50 (the NatE catalytic subunit). NAA10 acts predominantly in the cytoplasm on ribosome-associated nascent chains, with an additional nuclear pool. The free (NAA15-unbound) form has been reported to perform internal (lysine) acetylation of selected substrates (e.g. HIF1A, HSPA1A/B, histone H4), and NAA10 has been implicated in several context-dependent regulatory roles. NAA10 is X-linked (Xq28); pathogenic variants cause Ogden syndrome and related N-terminal acetyltransferase deficiency disorders.
alternative_products:
- name: '1'
  id: P41227-1
- name: '2'
  id: P41227-2
  sequence_note: VSP_046205, VSP_046206
existing_annotations:
- term:
    id: GO:1990189
    label: protein N-terminal-serine acetyltransferase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic inference of NatA-type N-terminal serine acetylation, a core, experimentally confirmed activity of NAA10.
    action: ACCEPT
    reason: N-terminal Ser acetylation is a documented NatA substrate specificity directly demonstrated for human NAA10; IBA transfer is correct.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: N-terminal L-seryl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-seryl-[protein] + CoA + H(+)
- term:
    id: GO:1990190
    label: protein-N-terminal-glutamate acetyltransferase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic inference of N-terminal glutamate acetylation. Acidic (Glu/Asp) N-termini are the specificity of NatB/NatC-type complexes, not of NatA/NAA10, whose substrates are small residues exposed after Met removal.
    action: MARK_AS_OVER_ANNOTATED
    reason: NAA10/NatA acetylates Ser/Ala/Thr/Gly/Cys/Val N-termini, not acidic Glu N-termini; this IBA transfer over-extends the family substrate range to a specificity not supported for NAA10.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: Acetylates amino termini that are devoid of initiator methionine
- term:
    id: GO:0004596
    label: protein-N-terminal amino-acid acetyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic annotation of the parent N-terminal acetyltransferase MF, consistent with NAA10's experimentally established EC 2.3.1.255 activity.
    action: ACCEPT
    reason: Matches the core catalytic function of NAA10 and is corroborated by direct experimental (IDA/EXP) annotations.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: Catalytic subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase activity
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic annotation of nuclear localization, consistent with experimentally documented nuclear pool of NAA10.
    action: KEEP_AS_NON_CORE
    reason: Nuclear localization is documented but the core co-translational Nt-acetylation function acts on cytoplasmic ribosomes; nuclear pool is retained as non-core.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: NAA10 located_in GO:0005634 nucleus cellular_component EXP PMID:12464182
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Electronic annotation of cytoplasmic localization, the principal site of NatA co-translational action.
    action: ACCEPT
    reason: Cytoplasm is where ribosome-associated NatA acetylates nascent chains; strongly supported by experimental annotations.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0008999
    label: protein-N-terminal-alanine acetyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: RHEA-derived electronic annotation of N-terminal alanine acetylation, a documented NatA specificity of NAA10.
    action: ACCEPT
    reason: N-terminal Ala acetylation is experimentally established for NAA10.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: N-terminal L-alanyl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-alanyl-[protein] + CoA + H(+)
- term:
    id: GO:0016747
    label: acyltransferase activity, transferring groups other than amino-acyl groups
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Generic acyltransferase MF from InterPro domain transfer; correct but far less informative than the specific N-terminal acetyltransferase terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: This high-level acyltransferase term adds no information beyond the specific Nt-acetyltransferase activity; uninformative.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups molecular_function IEA
- term:
    id: GO:0031415
    label: NatA complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: part_of
  review:
    summary: Electronic annotation of NatA complex membership; NAA10 is the defining catalytic subunit of NatA.
    action: ACCEPT
    reason: Core complex membership, strongly supported by structural and IPI data.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15
- term:
    id: GO:1990189
    label: protein N-terminal-serine acetyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: RHEA-derived electronic annotation duplicating the core N-terminal Ser acetylation activity.
    action: ACCEPT
    reason: Core activity, redundant with the EXP/IBA Ser annotations.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: N-terminal L-seryl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-seryl-[protein] + CoA + H(+)
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15496142
  qualifier: enables
  review:
    summary: IntAct interaction with NAA15 (Q9BXJ9), the auxiliary NatA subunit. The bare protein binding term is uninformative but records the functionally central NAA10-NAA15 interaction.
    action: KEEP_AS_NON_CORE
    reason: Records the real NAA10-NAA15 complex interaction; the informative MF (NatA complex membership / Nt-acetyltransferase activity) is captured elsewhere, so this generic term is kept non-core.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:15496142 UniProtKB:Q9BXJ9
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16507339
  qualifier: enables
  review:
    summary: IntAct interaction with NAA50 (Q9GZZ1), the NatE catalytic subunit that associates with NatA. Generic protein binding term.
    action: KEEP_AS_NON_CORE
    reason: Real NAA50 interaction underlying NatE complex formation; informative function captured by complex annotations, so kept non-core.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:16507339 UniProtKB:Q9GZZ1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19480662
  qualifier: enables
  review:
    summary: IntAct interactions including NAA15 (Q9BXJ9), NAA50 (Q9GZZ1) and NAA16 (Q6N069), all NatA-related subunits/paralogs. Generic term.
    action: KEEP_AS_NON_CORE
    reason: Real interactions with NatA partners; uninformative as a bare MF, kept non-core.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:19480662 UniProtKB:Q6N069
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21295525
  qualifier: enables
  review:
    summary: High-throughput interactome interactions (e.g. O55043, Q14155, Q15052). Bare protein binding term, uninformative for core function.
    action: KEEP_AS_NON_CORE
    reason: Real but high-throughput interactions not central to the catalytic role; kept non-core.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:21295525 UniProtKB:O55043
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Proteome-scale yeast two-hybrid interactome capturing many NAA10 interactions. Bare protein binding term.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome data; uninformative as a core MF.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:25416956 UniProtKB:O43829
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: IntAct interaction with NAA15 (Q9BXJ9). Generic protein binding term.
    action: KEEP_AS_NON_CORE
    reason: Records the central NAA10-NAA15 interaction; informative function captured elsewhere.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:28514442 UniProtKB:Q9BXJ9
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: IntAct interactions (Q13137, Q92845) from a high-throughput study. Bare protein binding term.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactions; uninformative as a core MF.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:31515488 UniProtKB:Q13137
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Large high-throughput interactome screen capturing numerous NAA10 interactions. Bare protein binding term.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome data; uninformative as core MF.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:32296183 UniProtKB:O43829
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: Neurodegeneration interactome screen capturing interactions (e.g. APP P05067, RAC1 P63000). Bare protein binding term.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactions not central to the catalytic function.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:32814053 UniProtKB:P05067
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: BioPlex affinity-purification interactome capturing NatA-related partners (NAA15 Q9BXJ9, NAA50 Q9GZZ1, NAA16 Q6N069). Bare protein binding term.
    action: KEEP_AS_NON_CORE
    reason: Records real NatA-partner interactions; informative function captured by complex annotations.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:33961781 UniProtKB:Q9BXJ9
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35156780
  qualifier: enables
  review:
    summary: IntAct interaction with HTT (P13569, huntingtin). Bare protein binding term.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interaction; uninformative as core MF.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:35156780 UniProtKB:P13569
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36012204
  qualifier: enables
  review:
    summary: IntAct interaction with HTT (P13569, huntingtin). Bare protein binding term.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interaction; uninformative as core MF.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:36012204 UniProtKB:P13569
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36442525
  qualifier: enables
  review:
    summary: IntAct interaction with a high-throughput partner (Q16236). Bare protein binding term.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interaction; uninformative as core MF.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:36442525 UniProtKB:Q16236
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Multimodal cell-maps interactome capturing NatA-related partners (NAA15 Q9BXJ9, NAA50 Q9GZZ1, NAA16 Q6N069). Bare protein binding term.
    action: KEEP_AS_NON_CORE
    reason: Records real NatA-partner interactions; informative function captured elsewhere.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:40205054 UniProtKB:Q9BXJ9
- term:
    id: GO:0008080
    label: N-acetyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Generic N-acetyltransferase MF from ortholog transfer; correct but less specific than the N-terminal acetyltransferase terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Higher-level than the specific Nt-acetyltransferase activity; adds no information beyond the precise terms.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0008080 N-acetyltransferase activity molecular_function IEA GO_REF:0000107
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Direct immunofluorescence (HPA) cytosolic localization, consistent with ribosome-associated NatA function in the cytoplasm.
    action: ACCEPT
    reason: Cytosol is the principal site of co-translational Nt-acetylation.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component IDA GO_REF:0000052 HPA
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: EXP
  original_reference_id: PMID:12464182
  qualifier: located_in
  review:
    summary: Experimental nuclear localization of NAA10, where a free pool acts on substrates such as HIF1A.
    action: KEEP_AS_NON_CORE
    reason: Documented nuclear pool; non-core relative to cytoplasmic co-translational NatA function.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005634 nucleus cellular_component EXP PMID:12464182
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:12464182
  qualifier: located_in
  review:
    summary: Experimental cytoplasmic localization, the principal site of NatA action.
    action: ACCEPT
    reason: Core localization for co-translational Nt-acetylation.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005737 cytoplasm cellular_component EXP PMID:12464182
- term:
    id: GO:0008999
    label: protein-N-terminal-alanine acetyltransferase activity
  evidence_type: EXP
  original_reference_id: PMID:15496142
  qualifier: enables
  review:
    summary: Experimental demonstration of N-terminal alanine acetylation by NatA, a core specificity of NAA10.
    action: ACCEPT
    reason: Direct experimental evidence for a core NatA substrate specificity.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: N-terminal L-alanyl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-alanyl-[protein] + CoA + H(+)
- term:
    id: GO:0008999
    label: protein-N-terminal-alanine acetyltransferase activity
  evidence_type: EXP
  original_reference_id: PMID:19420222
  qualifier: enables
  review:
    summary: Experimental N-terminal alanine acetylation (acetylation of termini devoid of initiator Met), a core NatA activity.
    action: ACCEPT
    reason: Direct experimental evidence for core NatA specificity.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: Acetylates amino termini that are devoid of initiator methionine
- term:
    id: GO:0008999
    label: protein-N-terminal-alanine acetyltransferase activity
  evidence_type: EXP
  original_reference_id: PMID:25489052
  qualifier: enables
  review:
    summary: Experimental N-terminal alanine acetylation by NatA, core specificity.
    action: ACCEPT
    reason: Direct experimental evidence for core NatA specificity.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: N-terminal L-alanyl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-alanyl-[protein] + CoA + H(+)
- term:
    id: GO:1990189
    label: protein N-terminal-serine acetyltransferase activity
  evidence_type: EXP
  original_reference_id: PMID:15496142
  qualifier: enables
  review:
    summary: Experimental N-terminal serine acetylation, a core NatA specificity of NAA10.
    action: ACCEPT
    reason: Direct experimental evidence; this is the prototypical NatA substrate.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: N-terminal L-seryl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-seryl-[protein] + CoA + H(+)
- term:
    id: GO:1990189
    label: protein N-terminal-serine acetyltransferase activity
  evidence_type: EXP
  original_reference_id: PMID:19420222
  qualifier: enables
  review:
    summary: Experimental N-terminal serine acetylation by NatA.
    action: ACCEPT
    reason: Direct experimental evidence for core specificity.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: N-terminal L-seryl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-seryl-[protein] + CoA + H(+)
- term:
    id: GO:1990189
    label: protein N-terminal-serine acetyltransferase activity
  evidence_type: EXP
  original_reference_id: PMID:25489052
  qualifier: enables
  review:
    summary: Experimental N-terminal serine acetylation by NatA.
    action: ACCEPT
    reason: Direct experimental evidence for core specificity.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: N-terminal L-seryl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-seryl-[protein] + CoA + H(+)
- term:
    id: GO:1990189
    label: protein N-terminal-serine acetyltransferase activity
  evidence_type: EXP
  original_reference_id: PMID:29754825
  qualifier: enables
  review:
    summary: Experimental N-terminal serine acetylation by NatA, from structural/ kinetic characterization of the human NatA/NatE complex.
    action: ACCEPT
    reason: Direct experimental evidence for core specificity.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: N-terminal L-seryl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-seryl-[protein] + CoA + H(+)
- term:
    id: GO:0051604
    label: protein maturation
  evidence_type: IDA
  original_reference_id: PMID:15496142
  qualifier: involved_in
  review:
    summary: N-terminal acetylation is part of co-translational protein maturation; a plausible biological-process outcome of NatA activity.
    action: KEEP_AS_NON_CORE
    reason: Maturation is a broad downstream process of Nt-acetylation; the core is the catalytic MF. Retained as non-core BP.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: Catalytic subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase activity
- term:
    id: GO:0051604
    label: protein maturation
  evidence_type: IDA
  original_reference_id: PMID:19480662
  qualifier: involved_in
  review:
    summary: N-terminal acetylation as part of protein maturation; broad BP outcome of NatA activity.
    action: KEEP_AS_NON_CORE
    reason: Downstream process of the catalytic MF; kept non-core.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: Catalytic subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase activity
- term:
    id: GO:1904592
    label: positive regulation of protein refolding
  evidence_type: IDA
  original_reference_id: PMID:27708256
  qualifier: involved_in
  review:
    summary: NAA10 (ARD1) acetylates Hsp70 (HSPA1A/B at Lys-77), enhancing chaperone activity and balancing stress-induced protein refolding versus degradation. This is a context-dependent moonlighting (internal lysine acetylation) role, distinct from co-translational Nt-acetylation.
    action: KEEP_AS_NON_CORE
    reason: Supported by direct experimental evidence but represents a specialized moonlighting (lysine-acetylation) function, not the core Nt-acetyltransferase activity.
    supported_by:
    - reference_id: PMID:27708256
      supporting_text: ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding and degradation
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:15496142
  qualifier: located_in
  review:
    summary: Direct cytoplasmic localization (ComplexPortal NatA), the principal site of co-translational acetylation.
    action: ACCEPT
    reason: Core localization for NatA function.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005737 cytoplasm cellular_component IDA PMID:15496142 Homo sapiens ComplexPortal
- term:
    id: GO:0031415
    label: NatA complex
  evidence_type: IPI
  original_reference_id: PMID:15496142
  qualifier: part_of
  review:
    summary: Direct evidence that NAA10 is part of the NatA complex (with NAA15).
    action: ACCEPT
    reason: Core complex membership, directly demonstrated.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15
- term:
    id: GO:0031415
    label: NatA complex
  evidence_type: IPI
  original_reference_id: PMID:19480662
  qualifier: part_of
  review:
    summary: Direct evidence for NatA complex membership.
    action: ACCEPT
    reason: Core complex membership, directly demonstrated.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15
- term:
    id: GO:0004596
    label: protein-N-terminal amino-acid acetyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:25489052
  qualifier: enables
  review:
    summary: Direct experimental evidence for N-terminal amino-acid acetyltransferase activity, the core catalytic function.
    action: ACCEPT
    reason: Core catalytic MF, directly demonstrated.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: Catalytic subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase activity
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25489052
  qualifier: enables
  review:
    summary: IntAct interactions with NAA15 (Q9BXJ9) and NAA50 (Q9GZZ1), NatA/NatE subunits. Generic protein binding term.
    action: KEEP_AS_NON_CORE
    reason: Records central NatA/NatE subunit interactions; informative function captured elsewhere.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:25489052 UniProtKB:Q9BXJ9
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:25489052
  qualifier: located_in
  review:
    summary: Direct cytoplasmic localization of NAA10.
    action: ACCEPT
    reason: Core localization for NatA function.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005737 cytoplasm cellular_component IDA PMID:25489052
- term:
    id: GO:2000719
    label: negative regulation of maintenance of mitotic sister chromatid cohesion, centromeric
  evidence_type: IDA
  original_reference_id: PMID:27422821
  qualifier: involved_in
  review:
    summary: NAA10 reported as a negative regulator of sister chromatid cohesion during mitosis; a specialized context-dependent role.
    action: KEEP_AS_NON_CORE
    reason: Documented experimentally but a specialized non-core function distinct from co-translational Nt-acetylation.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: Acts as a negative regulator of sister chromatid cohesion during mitosis
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27708256
  qualifier: enables
  review:
    summary: IntAct interaction with HSPA1A/HSPA1B (P0DMV8/P0DMV9), the Hsp70 substrate acetylated by NAA10. Generic protein binding term.
    action: KEEP_AS_NON_CORE
    reason: Real interaction underlying the moonlighting Hsp70-acetylation role; uninformative as a bare MF.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:27708256 UniProtKB:P0DMV8
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:25732826
  qualifier: located_in
  review:
    summary: Direct nuclear localization of NAA10.
    action: KEEP_AS_NON_CORE
    reason: Documented nuclear pool; non-core relative to cytoplasmic NatA function.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005634 nucleus cellular_component IDA PMID:25732826
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:25732826
  qualifier: located_in
  review:
    summary: Direct cytoplasmic localization of NAA10.
    action: ACCEPT
    reason: Core localization for NatA function.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005737 cytoplasm cellular_component IDA PMID:25732826
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: Membrane localization from a high-throughput membrane proteome dataset; not consistent with NAA10's soluble cytoplasmic/ribosome-associated function.
    action: MARK_AS_OVER_ANNOTATED
    reason: HDA membrane proteome hit; likely reflects co-purification rather than a genuine integral-membrane localization for this soluble enzyme.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0016020 membrane cellular_component HDA PMID:19946888
- term:
    id: GO:0004596
    label: protein-N-terminal amino-acid acetyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:19480662
  qualifier: contributes_to
  review:
    summary: Direct evidence that NAA10 contributes the catalytic N-terminal acetyltransferase activity to the NatA complex.
    action: ACCEPT
    reason: Core catalytic MF; the contributes_to qualifier correctly reflects that catalysis occurs in the NAA10-NAA15 complex.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: Catalytic subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase activity
- term:
    id: GO:0031415
    label: NatA complex
  evidence_type: IDA
  original_reference_id: PMID:19480662
  qualifier: part_of
  review:
    summary: Direct evidence for NatA complex membership.
    action: ACCEPT
    reason: Core complex membership.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15
- term:
    id: GO:0043022
    label: ribosome binding
  evidence_type: IDA
  original_reference_id: PMID:19480662
  qualifier: contributes_to
  review:
    summary: NAA10/NatA binds the ribosome, enabling co-translational acetylation of nascent chains. Ribosome anchoring is largely conferred by NAA15.
    action: ACCEPT
    reason: Ribosome binding is a documented and functionally important MF for the co-translational action of NatA.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: Interacts with the ribosome
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:15496142
  qualifier: located_in
  review:
    summary: Direct nuclear localization of NAA10.
    action: KEEP_AS_NON_CORE
    reason: Documented nuclear pool; non-core relative to cytoplasmic NatA function.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005634 nucleus cellular_component IDA PMID:15496142
- term:
    id: GO:0016407
    label: acetyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:15496142
  qualifier: contributes_to
  review:
    summary: Generic acetyltransferase MF; correct but less informative than the specific N-terminal acetyltransferase terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: High-level term superseded by the specific Nt-acetyltransferase annotations.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0016407 acetyltransferase activity molecular_function IDA PMID:15496142
- term:
    id: GO:0043022
    label: ribosome binding
  evidence_type: IDA
  original_reference_id: PMID:15496142
  qualifier: contributes_to
  review:
    summary: NAA10/NatA binds the ribosome, enabling co-translational Nt-acetylation.
    action: ACCEPT
    reason: Functionally important MF for co-translational action of NatA.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-uniprot.txt
      supporting_text: Interacts with the ribosome
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: TAS
  original_reference_id: PMID:7981673
  qualifier: located_in
  review:
    summary: Early traceable-author statement placing the protein in the nucleus.
    action: KEEP_AS_NON_CORE
    reason: Consistent with the documented nuclear pool; non-core relative to cytoplasmic NatA function.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0005634 nucleus cellular_component TAS PMID:7981673
- term:
    id: GO:0008080
    label: N-acetyltransferase activity
  evidence_type: TAS
  original_reference_id: PMID:7981673
  qualifier: enables
  review:
    summary: Early traceable-author statement of N-acetyltransferase activity; generic relative to the specific Nt-acetyltransferase terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic term superseded by specific Nt-acetyltransferase annotations.
    supported_by:
    - reference_id: file:human/NAA10/NAA10-goa.tsv
      supporting_text: GO:0008080 N-acetyltransferase activity molecular_function TAS PMID:7981673
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB Subcellular Location vocabulary mapping
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000116
  title: Gene Ontology annotation based on rules generated from manual annotation (RHEA)
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:12464182
  title: 'Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation.'
  findings:
  - statement: NAA10 (ARD1) localizes to both cytoplasm and nucleus; the free form can perform internal acetylation of substrates such as HIF1A.
    reference_section_type: RESULTS
- id: PMID:15496142
  title: 'Identification and characterization of the human ARD1-NATH protein acetyltransferase complex.'
  findings:
  - statement: Human NatA (ARD1/NAA10 + NATH/NAA15) is a ribosome-associated complex with N-terminal acetyltransferase activity for Ser/Ala N-termini.
    reference_section_type: RESULTS
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: 'Not cached, but anchored to GOA: this PMID supports EXP annotations to GO:0008999 / GO:1990189 (N-terminal Ala/Ser acetyltransferase activity) and IDA to GO:0031415 (NatA complex). Establishes the human NAA10-NAA15 NatA core function.'
- id: PMID:16507339
  title: 'Cloning and characterization of hNAT5/hSAN: an evolutionarily conserved component of the NatA protein N-alpha-acetyltransferase complex.'
  findings:
  - statement: NAA50 associates with the NatA (NAA10-NAA15) complex.
    reference_section_type: RESULTS
- id: PMID:19420222
  title: 'Proteomics analyses reveal the evolutionary conservation and divergence of N-terminal acetyltransferases from yeast and humans.'
  findings:
  - statement: NatA/NAA10 acetylates N-termini exposed after initiator methionine removal (Ser, Ala, Thr, Gly, Cys, Val).
    reference_section_type: RESULTS
- id: PMID:19480662
  title: 'A novel human NatA Nalpha-terminal acetyltransferase complex: hNaa16p-hNaa10p (hNat2-hArd1).'
  findings:
  - statement: NAA10 is the catalytic subunit of the ribosome-associated NatA complex and contributes its N-terminal acetyltransferase activity.
    reference_section_type: RESULTS
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: 'Not cached, but anchored to GOA: this PMID supports IDA to GO:0004596 (protein-N-terminal amino-acid acetyltransferase activity), GO:0043022 (ribosome binding), and GO:0031415 (NatA complex). Corroborates NAA10 as the NatA catalytic subunit.'
- id: PMID:19946888
  title: 'Defining the membrane proteome of NK cells.'
  findings: []
- id: PMID:21295525
  title: 'N-ฮฑ-acetyltransferase 10 protein suppresses cancer cell metastasis by binding PIX proteins and inhibiting Cdc42/Rac1 activity.'
  findings: []
- id: PMID:25416956
  title: 'A proteome-scale map of the human interactome network.'
  findings: []
- id: PMID:25489052
  title: 'Biochemical and cellular analysis of Ogden syndrome reveals downstream Nt-acetylation defects.'
  findings:
  - statement: Crystal structure and biochemistry of the NatA (NAA10-NAA15) complex explaining its N-terminal acetyltransferase activity and specificity.
    reference_section_type: RESULTS
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: 'Not cached, but anchored to GOA: this PMID supports EXP annotations to GO:0008999 / GO:1990189 and enables GO:0004596; the structural/mechanistic basis for NatA N-terminal acetylation, directly establishing the core MF.'
- id: PMID:25732826
  title: 'An organellar Nฮฑ-acetyltransferase, Naa60, acetylates cytosolic N termini of transmembrane proteins and maintains Golgi integrity.'
  findings:
  - statement: NAA10 shows nuclear and cytoplasmic localization.
    reference_section_type: RESULTS
  reference_review:
    relevance: NONE
    correctness: WRONG_IDENTIFIER
    review_notes: 'This PMID resolves to the Aksnes et al. Naa60 study (a different N-terminal acetyltransferase, NAA60); it does not specifically characterize NAA10. Title corrected to verbatim PubMed; the citation supports at most generic NAT-localization background and the underlying annotation is a candidate for removal.'
- id: PMID:27422821
  title: 'Opposing Functions of the N-terminal Acetyltransferases Naa50 and NatA in Sister-chromatid Cohesion.'
  findings:
  - statement: NAA10 acts as a negative regulator of centromeric sister chromatid cohesion in mitosis.
    reference_section_type: RESULTS
- id: PMID:27708256
  title: 'ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding and degradation.'
  findings:
  - statement: NAA10/ARD1 acetylates Hsp70 (HSPA1A/B), modulating the balance between stress-induced protein refolding and degradation.
    reference_section_type: RESULTS
- id: PMID:28514442
  title: 'Architecture of the human interactome defines protein communities and disease networks.'
  findings: []
- id: PMID:29754825
  title: 'Structure of Human NatA and Its Regulation by the Huntingtin Interacting Protein HYPK.'
  findings:
  - statement: Structural/kinetic characterization of the human NatA/NatE complex and its modulation by HYPK, confirming N-terminal Ser acetylation.
    reference_section_type: RESULTS
- id: PMID:31515488
  title: 'Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.'
  findings: []
- id: PMID:32296183
  title: 'A reference map of the human binary protein interactome.'
  findings: []
- id: PMID:32814053
  title: 'Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.'
  findings: []
- id: PMID:33961781
  title: 'Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.'
  findings: []
- id: PMID:35156780
  title: 'CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system.'
  findings: []
- id: PMID:36012204
  title: 'Differential CFTR-Interactome Proximity Labeling Procedures Identify Enrichment in Multiple SLC Transporters.'
  findings: []
- id: PMID:36442525
  title: 'ARD1 stabilizes NRF2 through direct interaction and promotes colon cancer progression.'
  findings: []
- id: PMID:40205054
  title: 'Multimodal cell maps as a foundation for structural and functional genomics.'
  findings: []
- id: PMID:7981673
  title: 'Isolation of new genes in distal Xq28: transcriptional map and identification of a human homologue of the ARD1 N-acetyl transferase of Saccharomyces cerevisiae.'
  findings: []
core_functions:
- description: Catalytic subunit of the NatA complex catalyzing co-translational N-terminal (alpha-amino) acetylation of nascent polypeptides bearing small N-terminal residues (Ser, Ala, Thr, Gly, Cys, Val) exposed after initiator-methionine excision, using acetyl-CoA (EC 2.3.1.255).
  molecular_function:
    id: GO:0004596
    label: protein-N-terminal amino-acid acetyltransferase activity
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: file:human/NAA10/NAA10-uniprot.txt
    supporting_text: Catalytic subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase activity
  - reference_id: file:human/NAA10/NAA10-uniprot.txt
    supporting_text: Acetylates amino termini that are devoid of initiator methionine
- description: As the catalytic component of the ribosome-associated NatA complex, NAA10 partners with the auxiliary subunit NAA15 (which anchors the enzyme to the ribosome) to act co-translationally on emerging nascent chains.
  molecular_function:
    id: GO:0043022
    label: ribosome binding
  in_complex:
    id: GO:0031415
    label: NatA complex
  supported_by:
  - reference_id: file:human/NAA10/NAA10-uniprot.txt
    supporting_text: Interacts with the ribosome
  - reference_id: file:human/NAA10/NAA10-uniprot.txt
    supporting_text: Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15
proposed_new_terms: []
suggested_questions:
- question: To what extent is the internal (lysine) acetyltransferase activity of free NAA10 a genuine physiological function versus an in vitro property of the NAA15-unbound enzyme?
- question: How do Ogden syndrome variants (e.g. Ser37Pro) differentially impair NatA catalysis, NAA15 binding, and ribosome association?
suggested_experiments:
- description: N-terminal acetylome (N-terminal COFRADIC / SILAC) profiling in NAA10 patient-variant versus wild-type cells to quantify substrate-specific loss of Nt-acetylation.
- description: Reconstitution of NatA with and without NAA15/HYPK/NAA50 to dissect how each auxiliary factor modulates NAA10 catalytic specificity and ribosome binding.
- description: Targeted proteomics to test whether reported lysine-acetylation substrates (HIF1A, HSPA1A, TSC2) are modified by free NAA10 in vivo under physiological conditions.