Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0031417 NatC complex	IBA GO_REF:0000033	ACCEPT	Summary: NAA30 is a constitutive subunit of the NatC complex. Phylogenetic inference across MAK3 orthologs supports this membership, which is also directly demonstrated experimentally. Reason: NatC complex membership is the defining cellular component of NAA30 and is well supported by both phylogenetic and direct experimental evidence. Supporting Evidence: file:human/NAA30/NAA30-uniprot.txt Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30.
GO:0004596 protein-N-terminal amino-acid acetyltransferase activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based electronic annotation of the catalytic N-terminal acetyltransferase activity, consistent with the experimentally demonstrated catalytic activity of NAA30/hMak3. Reason: NAA30 is the catalytic subunit of NatC; this MF is its core function and is corroborated by direct experimental (IDA) evidence. Supporting Evidence: file:human/NAA30/NAA30-uniprot.txt Catalytic subunit of the N-terminal acetyltransferase C (NatC) complex
GO:0005634 nucleus	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Electronic (UniProt SubCell) annotation of nuclear localization, mirroring the IDA nuclear localization reported by PMID:25732826. NatC predominantly acts in the cytoplasm on ribosomes; nuclear pool is a secondary location. Reason: Nuclear localization is experimentally reported but secondary to the cytoplasmic ribosome-associated site where NatC performs co-translational N-terminal acetylation. Supporting Evidence: file:human/NAA30/NAA30-uniprot.txt Nucleus {ECO:0000269\|PubMed:25732826}
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: Electronic (UniProt SubCell) annotation of cytoplasmic localization, the primary compartment for NatC co-translational activity. Reason: Cytoplasm is the principal, experimentally supported site of NatC action. Supporting Evidence: file:human/NAA30/NAA30-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm
GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Generic GNAT-domain acyltransferase parent term assigned by InterPro. The specific activity of NAA30 is protein N-terminal-methionine acetyltransferase activity, which this term over-generalizes. Reason: This is a broad GNAT-fold parent term less precise than the specific N-terminal acetyltransferase activity that is experimentally established for NAA30; the specific terms (GO:0004596 / GO:0120518) already capture the function. Supporting Evidence: file:human/NAA30/NAA30-goa.tsv GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups molecular_function ECO:0000256 IEA GO_REF:0000002 InterPro:IPR000182
GO:0031417 NatC complex	IEA GO_REF:0000117	ACCEPT	Summary: Rule-based (ARBA) electronic annotation of NatC complex membership, redundant with and consistent with stronger IDA/IPI/IBA evidence. Reason: Correct and well-corroborated NatC complex membership. Supporting Evidence: file:human/NAA30/NAA30-uniprot.txt Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30.
GO:0120518 protein N-terminal-methionine acetyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: EC 2.3.1.256-based annotation of the specific N-terminal-methionine acetyltransferase activity. This is the most precise molecular-function term for NAA30's catalytic activity (acetylation of retained N-terminal Met). NatC substrate specificity is distinct from NatA and NatB, since NatC acetylates proteins that retain the initiator methionine followed by hydrophobic/amphipathic residues (canonical Met-Leu, Met-Ile, Met-Phe, Met-Trp), the defining substrate class for this MF term. Reason: Most specific and accurate MF for the catalytic subunit; matches the documented EC number and Rhea reactions for NatC-mediated Met-N-terminal acetylation. Supporting Evidence: file:human/NAA30/NAA30-goa.tsv GO:0120518 protein N-terminal-methionine acetyltransferase activity molecular_function ECO:0000501 IEA GO_REF:0000120 file:human/NAA30/NAA30-deep-research-falcon.md NatC acetylates proteins that retain the initiator methionine followed by hydrophobic or amphipathic residues
GO:0005515 protein binding	IPI PMID:19398576 Knockdown of human N alpha-terminal acetyltransferase comple...	KEEP AS NON CORE	Summary: IntAct interaction with NAA35 (Q5VZE5), the NatC auxiliary subunit. The bare protein binding term is uninformative; the relevant interaction is NatC complex assembly. Reason: Records a genuine intra-complex interaction with the NAA35 auxiliary subunit, but the uninformative GO:0005515 term is non-core; NatC complex membership captures the meaningful content. Supporting Evidence: file:human/NAA30/NAA30-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19398576 UniProtKB:Q5VZE5
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	KEEP AS NON CORE	Summary: BioPlex interactome interaction with NAA35 (Q5VZE5). Uninformative bare protein binding term reflecting NatC complex assembly. Reason: Real interaction with the NAA35 auxiliary subunit; non-core as a bare protein binding annotation, subsumed by the NatC complex term. Supporting Evidence: file:human/NAA30/NAA30-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:33961781 UniProtKB:Q5VZE5
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 interaction with NAA35 (Q5VZE5). Uninformative bare protein binding term reflecting NatC complex assembly. Reason: Real interaction with the NAA35 auxiliary subunit; non-core as a bare protein binding annotation, subsumed by the NatC complex term. Supporting Evidence: file:human/NAA30/NAA30-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:40205054 UniProtKB:Q5VZE5
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: Direct immunofluorescence (HPA) evidence for cytosolic localization, consistent with the principal site of NatC action. Reason: IDA-supported cytosolic localization matching the cytoplasmic ribosome-associated site of NatC. Supporting Evidence: file:human/NAA30/NAA30-goa.tsv GO:0005829 cytosol cellular_component ECO:0000314 IDA GO_REF:0000052
GO:0005737 cytoplasm	NAS PMID:19398576 Knockdown of human N alpha-terminal acetyltransferase comple...	ACCEPT	Summary: Non-traceable author statement (ComplexPortal) of cytoplasmic localization, consistent with the experimentally documented cytoplasmic site of NatC. Reason: Consistent with the primary cytoplasmic localization of NatC; corroborated by IDA evidence. Supporting Evidence: file:human/NAA30/NAA30-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm
GO:0031417 NatC complex	IPI PMID:19398576 Knockdown of human N alpha-terminal acetyltransferase comple...	ACCEPT	Summary: ComplexPortal/IPI evidence that NAA30 is part of the NatC complex, from the study that identified the human NatC complex. Reason: Direct experimental support for NatC complex membership. Supporting Evidence: PMID:19398576 the catalytic subunit hMak3 and the auxiliary subunits hMak10 and hMak31
GO:0004596 protein-N-terminal amino-acid acetyltransferase activity	IDA PMID:37891180 N-terminal acetylation shields proteins from degradation and...	ACCEPT	Summary: Direct experimental evidence for NAA30's N-terminal acetyltransferase activity in the study showing NatC-mediated N-terminal acetylation shields proteins from degradation. NAA30 contains the catalytic GNAT fold and transfers an acetyl group from acetyl-CoA to the free alpha-amino group at the substrate N-terminus. Reason: Core catalytic molecular function of NAA30, directly demonstrated. Supporting Evidence: file:human/NAA30/NAA30-uniprot.txt Catalyzes acetylation of the N-terminal methionine residues of peptides beginning with Met-Leu-Ala and Met-Leu-Gly file:human/NAA30/NAA30-deep-research-falcon.md NAA30 catalyzes the irreversible transfer of an acetyl group from acetyl coenzyme A (acetyl-CoA) to the free α-amino group at the N-terminus of nascent protein chains
GO:0031417 NatC complex	IDA PMID:37891180 N-terminal acetylation shields proteins from degradation and...	ACCEPT	Summary: Direct experimental confirmation of NatC complex membership in the protein-shielding/longevity study. Reason: Well-supported NatC complex membership. Supporting Evidence: file:human/NAA30/NAA30-uniprot.txt Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30.
GO:0050821 protein stabilization	IDA PMID:37891180 N-terminal acetylation shields proteins from degradation and...	KEEP AS NON CORE	Summary: NatC-mediated N-terminal acetylation shields substrate proteins from N-degron-mediated degradation, thereby stabilizing them. Mechanistically, unacetylated Met-hydrophobic N-termini are recognized as N-degrons by the Arg/N-degron pathway E3 ligases (UBR1, UBR2, UBR4-KCMF1); NatC acetylation masks these N-termini. This is a downstream biological-process consequence of NAA30's catalytic activity. Reason: Protein stabilization is a real and experimentally supported outcome of NatC N-terminal acetylation, but it is a downstream process rather than NAA30's direct molecular function (the catalytic acetyltransferase activity is core). Supporting Evidence: file:human/NAA30/NAA30-uniprot.txt N- terminal acetylation protects proteins from ubiquitination and degradation by the N-end rule pathway file:human/NAA30/NAA30-deep-research-falcon.md N-terminal acetylation by NatC shields these hydrophobic N-termini from recognition by the degradation machinery
GO:0005634 nucleus	IDA PMID:25732826 An organellar nα-acetyltransferase, naa60, acetylates cytoso...	KEEP AS NON CORE	Summary: Direct experimental evidence for a nuclear pool of NAA30. NatC predominantly acts cotranslationally in the cytoplasm; the nuclear localization is secondary. Reason: Experimentally observed nuclear localization, but secondary to the cytoplasmic ribosome-associated site of NatC function. Supporting Evidence: file:human/NAA30/NAA30-uniprot.txt Nucleus {ECO:0000269\|PubMed:25732826}
GO:0005737 cytoplasm	IDA PMID:25732826 An organellar nα-acetyltransferase, naa60, acetylates cytoso...	ACCEPT	Summary: Direct experimental evidence for cytoplasmic localization of NAA30, the primary site of NatC action. Reason: Cytoplasm is the principal, experimentally supported compartment of NatC. Supporting Evidence: file:human/NAA30/NAA30-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm
GO:0004596 protein-N-terminal amino-acid acetyltransferase activity	IDA PMID:19398576 Knockdown of human N alpha-terminal acetyltransferase comple...	ACCEPT	Summary: Direct in vitro demonstration that hMak3/NAA30 acetylates Met-Leu protein N-termini, establishing its catalytic N-terminal acetyltransferase activity. Reason: Core catalytic molecular function of NAA30, directly demonstrated in vitro. Supporting Evidence: PMID:19398576 hMak3 acetylates Met-Leu protein N termini in vitro
GO:0005737 cytoplasm	IDA PMID:19398576 Knockdown of human N alpha-terminal acetyltransferase comple...	ACCEPT	Summary: Direct experimental cytoplasmic localization of NAA30, consistent with ribosome-associated NatC activity. NatC functions co-translationally at the ribosome, positioned to acetylate nascent chains as they emerge from the exit tunnel. Reason: Cytoplasm is the principal experimentally supported compartment of NatC. Supporting Evidence: PMID:19398576 This complex associates with ribosomes file:human/NAA30/NAA30-deep-research-falcon.md Human NatC subunits co-sediment with ribosomes, and structural studies identified a ribosome-binding patch in the elongated tip region of the NatC complex
GO:0031417 NatC complex	IDA PMID:19398576 Knockdown of human N alpha-terminal acetyltransferase comple...	ACCEPT	Summary: Direct experimental identification of NAA30 (hMak3) as the catalytic subunit of the human NatC complex. Reason: Defining cellular component, directly demonstrated. Supporting Evidence: PMID:19398576 the catalytic subunit hMak3 and the auxiliary subunits hMak10 and hMak31
GO:0006474 N-terminal protein amino acid acetylation	IDA PMID:19398576 Knockdown of human N alpha-terminal acetyltransferase comple...	NEW	Summary: NAA30/hMak3 is the catalytic subunit of human NatC, which performs cotranslational N-terminal acetylation of protein substrates. Reason: PN correctly flagged that the review captures the NatC MF and CC but lacks the complementary BP term for the acetylation process itself. This is appropriate for the catalytic subunit. Supporting Evidence: PMID:19398576 hMak3 acetylates Met-Leu protein N termini in vitro PMID:19398576 the human NatC complex functions in cotranslational N-terminal acetylation

Core Functions

Catalytic subunit of the NatC N-terminal acetyltransferase complex that transfers acetyl groups from acetyl-CoA to the alpha-amino group of N-terminal methionine residues retained in front of bulky/hydrophobic residues (Met-Leu, Met-Ile, Met-Phe, Met-Trp, Met-Tyr), acting co-translationally on ribosome-bound nascent chains.

Molecular Function:

protein N-terminal-methionine acetyltransferase activity

Directly Involved In:

N-terminal protein amino acid acetylation

Cellular Locations:

cytoplasm

In Complex:

NatC complex

Supporting Evidence:

file:human/NAA30/NAA30-uniprot.txt
Catalytic subunit of the N-terminal acetyltransferase C (NatC) complex
PMID:19398576
hMak3 acetylates Met-Leu protein N termini in vitro

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/Swiss-Prot Subcellular Location vocabulary mapping

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:19398576

Knockdown of human N alpha-terminal acetyltransferase complex C leads to p53-dependent apoptosis and aberrant human Arl8b localization.

The human NatC complex contains the catalytic subunit hMak3 (NAA30) and auxiliary subunits hMak10 (NAA35) and hMak31 (NAA38); it associates with ribosomes and hMak3 acetylates Met-Leu protein N-termini in vitro.
Knockdown of NatC subunits results in p53-dependent cell death and aberrant ARL8B localization, indicating ARL8B is a NatC substrate in vivo.

PMID:25732826

An organellar nα-acetyltransferase, naa60, acetylates cytosolic N termini of transmembrane proteins and maintains Golgi integrity.

Reports cytoplasmic and nuclear localization data for NAA30 alongside characterization of the Golgi-associated NAT NAA60.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:37891180

N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity.

NatC-mediated N-terminal acetylation shields substrate proteins from N-degron-dependent ubiquitination and degradation, promoting protein stabilization, motility and longevity.

PMID:40205054

Multimodal cell maps as a foundation for structural and functional genomics.

file:human/NAA30/NAA30-deep-research-falcon.md

Falcon deep research report for NAA30

NAA30 is the catalytic GNAT-fold subunit of the heterotrimeric NatC complex (NAA30 catalytic, NAA35 large auxiliary/ribosome-anchoring, NAA38 small auxiliary) that co-translationally acetylates the alpha-amino group of N-terminal methionines retained in front of hydrophobic/amphipathic residues (Met-Leu, Met-Ile, Met-Phe, Met-Trp).
NatC-mediated N-terminal acetylation shields hydrophobic Met-starting N-termini from recognition as N-degrons by the Arg/N-degron pathway E3 ligases (UBR1, UBR2, UBR4-KCMF1), protecting substrates from proteasomal degradation; validated human NatC substrates include the trafficking GTPase ARL8B.

Suggested Experiments

Experiment: Quantitative N-terminomics of NAA30-knockout versus wild-type human cells to define the NatC-dependent N-terminal acetylome.

Experiment: Reconstituted in vitro acetylation assays with recombinant NatC (NAA30/NAA35/NAA38) on a panel of Met-X peptides to quantify substrate specificity and the contribution of each auxiliary subunit.

Experiment: Degradation/stability assays (e.g. cycloheximide chase, tandem fluorescent timer reporters) on defined NatC substrates in NAA30-depleted cells to test the N-degron-shielding model in human cells.

Deep Research

Falcon

(NAA30-deep-research-falcon.md)

Comprehensive Research Report: Human NAA30 (N-alpha-acetyltransferase 30) Falcon Edison Scientific Literature 26 citations 1 artifacts 2026-06-20T06:40:20.787590

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Comprehensive Research Report: Human NAA30 (N-alpha-acetyltransferase 30)

Gene Identity and Overview

Human NAA30 (also known as MAK3 or NAT12, UniProt accession Q147X3) encodes the catalytic subunit of the N-terminal acetyltransferase C (NatC) complex (aksnes2023natsata pages 1-2, drazic2021humannaa30can pages 1-2). NAA30 belongs to the GCN5-related N-acetyltransferase (GNAT) superfamily and functions in N-terminal protein acetylation, one of the most abundant post-translational modifications in eukaryotes (aksnes2023natsata pages 1-2, aksnes2019cotranslationalposttranslationaland pages 1-2). The gene and its enzymatic function are highly conserved from yeast to humans, with human NAA30 capable of functionally replacing yeast Mak3 in complementation assays (drazic2021humannaa30can pages 1-2, drazic2021humannaa30can pages 2-3).

Primary Catalytic Function and Reaction Mechanism

Enzymatic Activity

NAA30 catalyzes the irreversible transfer of an acetyl group from acetyl coenzyme A (acetyl-CoA) to the free α-amino group at the N-terminus of nascent protein chains (grunwald2020divergentarchitectureof pages 1-2, damme2016arolefor pages 1-7, aksnes2019cotranslationalposttranslationaland pages 1-2). This reaction can be described as: protein N-terminus + acetyl-CoA → N-acetyl-protein + CoA. The modification is considered irreversible, as no N-terminal deacetylase has been identified to date (aksnes2019cotranslationalposttranslationaland pages 1-2). NAA30 contains the characteristic GNAT fold required for its catalytic activity (grunwald2020divergentarchitectureof pages 1-2, grunwald2020divergentarchitectureof pages 2-3).

The NatC Complex Composition and Structure

NAA30 does not function alone but operates as part of a heterotrimeric complex consisting of three subunits: NAA30 (the catalytic subunit), NAA35 (the large auxiliary/ribosome-anchoring subunit), and NAA38 (the small auxiliary subunit) (grunwald2020divergentarchitectureof pages 1-2, deng2021molecularmechanismof pages 1-3, aksnes2023natsata pages 2-3). All three subunits are required for normal NatC acetylation activity in vivo (deng2021molecularmechanismof pages 1-3, deng2021molecularmechanismof pages 3-4).

Recent structural studies have revealed the molecular architecture of the NatC complex. The 2020 crystal structure of the Saccharomyces cerevisiae NatC complex showed a strikingly different architecture compared to other N-terminal acetyltransferases (grunwald2020divergentarchitectureof pages 1-2). NAA30 adopts the typical GNAT fold with a conserved CoA-binding motif (grunwald2020divergentarchitectureof pages 2-3). The large auxiliary subunit NAA35 is mostly α-helical and wraps around NAA30 and NAA38, forming an elongated structure with a distinctive "tip" region (grunwald2020divergentarchitectureof pages 1-2, grunwald2020divergentarchitectureof pages 2-3). NAA38 adopts an Sm fold similar to spliceosomal proteins (grunwald2020divergentarchitectureof pages 1-2). The three subunits together create a tunnel in the center of the complex that accommodates the substrate's first four amino acids at the NAA30-NAA35 interface (grunwald2020divergentarchitectureof pages 1-2).

The auxiliary subunits play critical roles beyond structural scaffolding. NAA35 serves as the ribosome anchor, positioning NatC directly underneath the ribosomal exit tunnel for co-translational acetylation (grunwald2020divergentarchitectureof pages 1-2, grunwald2020divergentarchitectureof pages 2-3). NAA38, while initially thought to be dispensable in some contexts, has been shown to increase thermostability and broaden the substrate specificity profile of NatC (aksnes2023natsata pages 1-2, aksnes2023natsata pages 2-3). Recent cryo-EM structures of human NatC complexes with and without NAA38 confirmed that NAA38 affects structural features of both NAA30 and NAA35 (aksnes2023natsata pages 2-3). Inositol hexaphosphate (IP6) has been identified as a stabilizing ligand that binds tightly to NatC and contributes to complex integrity (deng2021molecularmechanismof pages 1-3, deng2021molecularmechanismof pages 3-4).

Substrate Specificity

N-Terminal Sequence Recognition

NatC displays distinctive substrate specificity compared to other N-terminal acetyltransferases. While NatA acetylates small N-terminal residues exposed after methionine removal, and NatB acetylates methionine followed by acidic residues (MD, ME, MN, MQ), NatC acetylates proteins that retain the initiator methionine followed by hydrophobic or amphipathic residues (grunwald2020divergentarchitectureof pages 1-2, aksnes2023natsata pages 2-3, drazic2021humannaa30can pages 2-3).

The canonical human NatC substrate N-terminal sequences include Met-Leu (ML), Met-Ile (MI), Met-Phe (MF), and Met-Trp (MW) (damme2016arolefor pages 1-7, drazic2021humannaa30can pages 2-3). However, proteome-wide studies have expanded this substrate profile to include Met-Val (MV), Met-His (MH), Met-Lys (MK), and Met-Met (MM) N-termini (damme2016arolefor pages 1-7, aksnes2023natsata pages 2-3, damme2016arolefor pages 10-14). Recent yeast studies identified 57 NatC substrates, including some with Met-Tyr (MY), Met-Ala (MA), and Met-Ser (MS) N-termini, indicating even broader specificity than initially appreciated (damme2023expandedinvivo pages 1-2).

Structural analyses revealed that the first four amino acids of substrates contribute to NatC recognition at the NAA30-NAA35 interface (grunwald2020divergentarchitectureof pages 1-2). A sequence-specific, ligand-induced conformational change in NAA30 enables efficient acetylation (grunwald2020divergentarchitectureof pages 1-2). This mechanism differs from NatA and NatB, highlighting the divergent evolution of NAT complexes to recognize distinct substrate pools.

Substrate Coverage and Identified Targets

Proteome-wide N-terminomics studies have identified specific NatC substrates. In human cells, NAA30 knockdown experiments combined with positional proteomics identified 46 human NatC substrates whose N-terminal acetylation decreased upon NAA30 depletion (damme2016arolefor pages 1-7, damme2016arolefor pages 10-14). In yeast, 57 NatC substrates were identified using similar approaches (damme2023expandedinvivo pages 1-2). Notably, NatC-type proteins are often only partially acetylated across the cellular protein pool, unlike the near-complete acetylation observed for many NatB substrates (aksnes2023natsata pages 2-3, damme2023expandedinvivo pages 1-2).

Key identified substrates include:

Trafficking proteins: ARL8B (important for lysosomal localization) and ARFRP1/Arl3 (Golgi targeting dependent on acetylation and interaction with the membrane protein SYS1) (damme2016arolefor pages 1-7, varland2023nterminalacetylationshields pages 1-2, varland2023nterminalacetylationshields pages 2-3).

Neddylation machinery: UBE2M/UBC12 and UBE2F, the NEDD8-conjugating E2 enzymes critical for cullin neddylation. Their N-terminal acetylation promotes protein stability and productive interactions with cognate E3 ligases such as DCN1 by allowing burial of the acetylated N-terminus into hydrophobic pockets (varland2023nterminalacetylationshields pages 1-2, aksnes2023natsata pages 3-4).

Mitochondrial proteins: Multiple mitochondrial or organellar proteins were identified among NatC substrates or showed reduced expression upon NAA30 depletion (damme2016arolefor pages 1-7, damme2016arolefor pages 10-14). Computational analysis revealed that mitochondrial targeting sequences (MTS) show strong overrepresentation of NatC-compatible hydrophobic residues at position 2 (nashed2023functionalmappingof pages 1-3).

Subcellular Localization

NAA30 functions primarily as a ribosome-associated, co-translational enzyme in the cytosol (grunwald2020divergentarchitectureof pages 1-2, damme2016arolefor pages 1-7, grunwald2020divergentarchitectureof pages 2-3). Human NatC subunits co-sediment with ribosomes, and structural studies identified a ribosome-binding patch in the elongated tip region of the NatC complex (grunwald2020divergentarchitectureof pages 1-2). This positioning directly underneath the ribosomal exit tunnel enables the complex to acetylate nascent polypeptide chains as they emerge from the ribosome (grunwald2020divergentarchitectureof pages 2-3).

Interestingly, a truncated/splice-associated nuclear isoform of NAA30 has been reported in specific cancer contexts, particularly in glioblastoma-initiating cells and thyroid cancer tissues (grunwald2020divergentarchitectureof pages 1-2, aksnes2023natsata pages 1-2). This nuclear localization appears specific to certain cellular contexts and represents a deviation from the typical ribosome-associated function.

Biological Processes and Biochemical Pathways

Protein Quality Control and the Arg/N-Degron Pathway

One of the most significant recent discoveries is that NatC-mediated N-terminal acetylation serves as a protective mechanism against protein degradation (varland2023nterminalacetylationshields pages 1-2, varland2023nterminalacetylationshields pages 2-3). Genome-wide CRISPR knockout screens in human HAP1 cells revealed strong genetic interactions between NatC subunits and components of the Arg/N-degron pathway, particularly the E3 ubiquitin ligases UBR4-KCMF1, UBR1, and UBR2 (varland2023nterminalacetylationshields pages 1-2, varland2023nterminalacetylationshields pages 2-3, varland2023nterminalacetylationshields pages 3-4).

The molecular mechanism is now understood: unacetylated proteins bearing an N-terminal methionine followed by a hydrophobic residue are recognized by these ubiquitin ligases as N-degrons and targeted for proteasomal degradation (varland2023nterminalacetylationshields pages 1-2, varland2023nterminalacetylationshields pages 3-4). N-terminal acetylation by NatC shields these hydrophobic N-termini from recognition by the degradation machinery (varland2023nterminalacetylationshields pages 1-2, varland2023nterminalacetylationshields pages 2-3). Remarkably, NatC knockout-induced protein degradation and cellular phenotypes can be reversed by UBR knockdown, demonstrating the central importance of this interplay (varland2023nterminalacetylationshields pages 1-2, varland2023nterminalacetylationshields pages 2-3, varland2023nterminalacetylationshields pages 3-4).

Cullin Neddylation

NatC plays a critical role in the cullin neddylation pathway through acetylation of the NEDD8-conjugating enzymes UBE2M and UBE2F (varland2023nterminalacetylationshields pages 1-2, aksnes2023natsata pages 3-4). Acetylation of these E2 enzymes serves dual functions: it protects them from degradation and increases their affinity for E3 ligases, promoting efficient cullin neddylation (varland2023nterminalacetylationshields pages 1-2). Structural analysis showed that the acetylated N-terminus of UBE2M is buried within a hydrophobic pocket of DCN1, enhancing cullin neddylation activity (varland2023nterminalacetylationshields pages 1-2). This acetylation-dependent interaction can be antagonized by small molecule inhibitors, suggesting potential therapeutic applications.

Mitochondrial Function and Integrity

NAA30/NatC is essential for mitochondrial integrity and function (damme2016arolefor pages 1-7, aksnes2023natsata pages 3-4, damme2016arolefor pages 10-14). Knockdown of NAA30 in human cells causes mitochondrial fragmentation and loss of mitochondrial membrane potential (damme2016arolefor pages 1-7, aksnes2023natsata pages 3-4, damme2016arolefor pages 10-14). These effects occur independently of p53 pathways and are accompanied by reduced expression levels of mitochondrial matrix proteins (damme2016arolefor pages 1-7, damme2016arolefor pages 10-14).

The molecular basis for this mitochondrial requirement is becoming clearer. Computational analysis revealed that mitochondrial targeting sequences (MTS) show specific overrepresentation of hydrophobic residues at position 2, matching the NatC substrate profile (nashed2023functionalmappingof pages 1-3). Systematic mutagenesis of position 2 in a yeast mitochondrial protein confirmed its critical role in mitochondrial protein import (nashed2023functionalmappingof pages 1-3). These findings provide a molecular explanation for mitochondrial defects observed in NatC-depleted cells across species (nashed2023functionalmappingof pages 1-3).

Consistent with these cellular observations, yeast NatC mutants show poor growth on non-fermentable carbon sources like glycerol and ethanol, indicating mitochondrial dysfunction (drazic2021humannaa30can pages 1-2, drazic2021humannaa30can pages 2-3, damme2023expandedinvivo pages 1-2). Similarly, plant NatC (AtNAA30) is required for efficient photosynthesis in chloroplasts (drazic2021humannaa30can pages 2-3).

Golgi and Vesicle Trafficking

NatC is intimately involved in Golgi vesicle transport and the secretory pathway (varland2023nterminalacetylationshields pages 2-3, varland2023nterminalacetylationshields pages 3-4). CRISPR genetic interaction screens identified negative genetic interactions between NAA35 and genes involved in Golgi vesicle transport, endosomal transport, and virion assembly (varland2023nterminalacetylationshields pages 2-3, varland2023nterminalacetylationshields pages 3-4). Key interacting genes include ARL1, ARFRP1, SYS1, RAB1A/B, RAB2A, RAB14, and components of the conserved oligomeric Golgi (COG) complex (COG5, COG7) (varland2023nterminalacetylationshields pages 2-3, varland2023nterminalacetylationshields pages 3-4).

The molecular mechanism involves NatC-mediated acetylation of small GTPases. For example, ARFRP1/Arl3 requires N-terminal acetylation for correct targeting to the trans-Golgi network, mediated by interaction of the acetylated N-terminus with the membrane protein SYS1 (varland2023nterminalacetylationshields pages 1-2, drazic2021humannaa30can pages 2-3, varland2023nterminalacetylationshields pages 2-3). Similarly, ARL8B depends on NAA30-mediated acetylation for lysosomal localization (damme2016arolefor pages 1-7, varland2023nterminalacetylationshields pages 1-2). Depletion of human NAA30 induces fragmentation of the Golgi stack, suggesting additional NatC targets at the Golgi beyond ARFRP1 (grunwald2020divergentarchitectureof pages 1-2, grunwald2020divergentarchitectureof pages 2-3).

Cell Proliferation, Survival, and Development

NAA30 contributes to cell growth, survival, and organismal development (grunwald2020divergentarchitectureof pages 1-2, aksnes2023natsata pages 2-3, aksnes2023natsata pages 3-4). Knockdown of NAA30 in human cells leads to stabilization of p53 and induction of downstream proapoptotic genes, resulting in apoptosis (aksnes2023natsata pages 2-3, aksnes2023natsata pages 3-4). In glioblastoma-initiating cells, NAA30 knockdown reduces cell viability, sphere-forming ability, and hypoxia tolerance (grunwald2020divergentarchitectureof pages 1-2, aksnes2023natsata pages 2-3). Mice transplanted with NAA30-knockdown glioblastoma cells show prolonged survival compared to controls, suggesting NAA30 as a potential therapeutic target in cancer (grunwald2020divergentarchitectureof pages 1-2).

Developmental roles are evident across species. Zebrafish knockouts of NAA30 or NAA35 led to decreased cell proliferation, increased apoptosis, and poor blood vessel formation, resulting in embryonic lethality (grunwald2020divergentarchitectureof pages 2-3). In Drosophila melanogaster, loss of NatC is associated with male sterility, reduced longevity, and age-dependent loss of motility due to developmental muscle defects (varland2023nterminalacetylationshields pages 1-2, varland2023nterminalacetylationshields pages 2-3). Remarkably, muscle-specific overexpression of UbcE2M (Drosophila UBE2M homolog) suppresses the longevity and motility defects of NatC deletion, demonstrating the functional importance of protecting this key substrate from degradation (varland2023nterminalacetylationshields pages 1-2, varland2023nterminalacetylationshields pages 2-3).

In Caenorhabditis elegans, NatC appears to play a regulatory role in response to nutrient availability and stress, coordinating the balance between growth/development and stress responses/energy-saving quiescence (aksnes2023natsata pages 3-4).

Stress Responses and Aging

NatC function is linked to stress resistance and aging across multiple organisms (drazic2021humannaa30can pages 1-2, varland2023nterminalacetylationshields pages 1-2, drazic2021humannaa30can pages 2-3). Yeast NatC mutants display osmotic sensitivity and reduced growth under high salt stress (drazic2021humannaa30can pages 2-3, damme2023expandedinvivo pages 1-2). In plants, drought stress downregulates NatA while NatC appears involved in adaptive responses (aksnes2019cotranslationalposttranslationaland pages 1-2).

Most compellingly, recent studies demonstrate that NatC-mediated N-terminal acetylation acts as a protective mechanism relevant for increased longevity and motility in aging organisms (varland2023nterminalacetylationshields pages 1-2, varland2023nterminalacetylationshields pages 2-3). The protection of proteins from degradation, particularly in muscle tissue, contributes to healthy aging phenotypes.

Disease Relevance

NAA30 is increasingly implicated in human disease, particularly cancer (grunwald2020divergentarchitectureof pages 1-2, aksnes2023natsata pages 1-2, aksnes2023natsata pages 2-3). Strong upregulation of NAA30 has been observed in glioblastoma samples at the protein level (grunwald2020divergentarchitectureof pages 1-2, aksnes2023natsata pages 2-3). High NAA30 expression is associated with poor survival in certain cancer types (aksnes2023natsata pages 2-3). Additionally, a likely pathogenic NAA30 variant has been suggested to cause global developmental delay and tracheal cleft, underscoring the importance of NAA30 function in human development (varland2023nterminalacetylationshields pages 1-2, varland2023nterminalacetylationshields pages 2-3).

Loss-of-function variants in genes encoding acetyltransferases can lead to congenital disorders characterized by intellectual disability and heart/muscle defects (keller2024acetyltransferaseincardiovascular pages 1-3). While most pathogenic NAT variants identified to date affect NatA subunits (NAA10, NAA15) or NatB subunits (NAA20), the identification of disease-associated NAA30 variants suggests that systematic screening of NAT genes in developmental disorders is warranted.

Summary of Key Findings

Category	Summary	Key specifics/examples	Evidence
Gene/protein identity	Human NAA30 (also called MAK3, NAT12) is the catalytic subunit of the NatC N-terminal acetyltransferase complex. It belongs to the GNAT-family acetyltransferases and functions in co-translational protein N-terminal acetylation.	NatC is conserved from yeast to human; human NAA30 can functionally replace yeast Mak3/Naa30 in complementation assays.	(drazic2021humannaa30can pages 1-2, damme2016arolefor pages 1-7, aksnes2019cotranslationalposttranslationaland pages 1-2)
Enzymatic reaction	NAA30 catalyzes transfer of an acetyl group from acetyl-CoA to the free α-amino group at the protein N-terminus of nascent substrates.	Reaction: protein N-terminus + acetyl-CoA → N-acetyl-protein + CoA; modification is generally considered irreversible.	(grunwald2020divergentarchitectureof pages 1-2, damme2016arolefor pages 1-7, aksnes2019cotranslationalposttranslationaland pages 1-2)
NatC complex composition	NatC is a heterotrimeric complex composed of NAA30 (catalytic), NAA35 (large auxiliary/ribosome-anchoring subunit), and NAA38 (small auxiliary subunit).	Structural work shows NAA30 adopts the GNAT fold; NAA35 and NAA38 stabilize the complex; NAA38 broadens substrate specificity and increases thermostability.	(grunwald2020divergentarchitectureof pages 1-2, deng2021molecularmechanismof pages 1-3, aksnes2023natsata pages 2-3, grunwald2020divergentarchitectureof pages 2-3)
Substrate specificity: general rule	NatC acetylates proteins that retain the initiator methionine and usually have a hydrophobic or amphipathic residue at position 2. Residues at positions 3-4 also contribute to recognition.	Human NatC/NAA30 is described as modifying Met-starting proteins not targeted by NatB. Structural studies indicate the first four substrate residues contribute to recognition.	(grunwald2020divergentarchitectureof pages 1-2, deng2021molecularmechanismof pages 1-3, aksnes2023natsata pages 2-3, varland2023nterminalacetylationshields pages 1-2)
Substrate specificity: canonical human sequences	Canonical human NatC-type N-termini include ML, MI, MF, MW and expanded in vivo classes include MV, MH, MK, MM.	The 2016 human N-terminomics study identified 46 direct/likely human NatC substrates and expanded specificity beyond the classic ML/MI/MF/MW set.	(damme2016arolefor pages 1-7, damme2016arolefor pages 10-14)
Substrate specificity: broader recent view	Recent reviews also summarize human NatC substrates as including ML, MI, MF, MV, MY, MW, MH, MK; yeast work shows overlap and some redundancy with NatE/Naa50 for certain methionine-starting N-termini.	This indicates NatC specificity is broader than originally appreciated, though not every compatible N-terminus is fully acetylated in vivo.	(aksnes2023natsata pages 2-3, damme2023expandedinvivo pages 1-2)
Acetylation coverage and scale	NatC is one of the major human NATs and, together with NatE/F, covers a substantial subset of methionine-retaining proteins; human cells showed 46 NAA30-dependent substrates and yeast 57 NatC substrates in proteome-scale analyses.	NatC-type proteins are often only partially acetylated across the cellular protein pool, unlike many NatB substrates.	(aksnes2023natsata pages 2-3, damme2023expandedinvivo pages 1-2, damme2016arolefor pages 10-14)
Known substrate examples: trafficking proteins	NAA30/NatC acetylates proteins involved in membrane trafficking and organelle targeting.	ARL8B/hArl8b is a validated human NatC substrate important for lysosomal localization; ARFRP1/Arl3 localization to Golgi depends on NatC-mediated N-terminal acetylation and interaction with SYS1.	(damme2016arolefor pages 1-7, varland2023nterminalacetylationshields pages 1-2, drazic2021humannaa30can pages 2-3, varland2023nterminalacetylationshields pages 2-3)
Known substrate examples: neddylation pathway	NatC-mediated acetylation is important for the cullin neddylation machinery.	UBE2M/UBC12 and UBE2F are particularly important NatC-relevant targets; their N-terminal acetylation promotes stability and productive interaction with cognate E3 ligases such as DCN1.	(varland2023nterminalacetylationshields pages 1-2, aksnes2023natsata pages 3-4)
Known substrate examples: mitochondrial/organellar proteins	Proteomics and phenotype analyses indicate that multiple mitochondrial or organellar proteins are directly or indirectly affected by NAA30 loss.	Human NAA30 depletion reduced levels of several mitochondrial proteins; some were identified among NatC substrates in organellar fractions.	(damme2016arolefor pages 1-7, damme2016arolefor pages 10-14)
Subcellular localization of function	NAA30 primarily functions as a ribosome-associated, co-translational enzyme in the cytosol as part of NatC.	Human NatC subunits co-sediment with ribosomes; structural work identified a ribosome-binding patch in NatC. A truncated/splice-associated nuclear NAA30 isoform has also been reported in some cancer contexts.	(grunwald2020divergentarchitectureof pages 1-2, damme2016arolefor pages 1-7, grunwald2020divergentarchitectureof pages 2-3)
Pathway/process: protein quality control	A major current model is that NatC-mediated N-terminal acetylation shields hydrophobic Met-starting proteins from degradation by the Arg/N-degron pathway.	Unacetylated NatC-type N-termini are recognized by UBR4-KCMF1, UBR1, and UBR2; NatC knockout phenotypes can be reversed by disrupting these ubiquitin ligases.	(varland2023nterminalacetylationshields pages 1-2, aksnes2023natsata pages 3-4, varland2023nterminalacetylationshields pages 3-4)
Pathway/process: Golgi and vesicle trafficking	NatC is linked to Golgi vesicle transport, endosomal transport, and secretory pathway organization.	CRISPR genetic interaction screens in human cells found negative interactions with ARL1, ARFRP1, SYS1, RAB1A/B, RAB2A, RAB14, COG5, COG7 and enrichment for Golgi vesicle transport pathways.	(varland2023nterminalacetylationshields pages 2-3, varland2023nterminalacetylationshields pages 3-4)
Pathway/process: mitochondrial integrity	NatC/NAA30 supports mitochondrial membrane potential, morphology, and likely import/biogenesis of selected proteins.	NAA30 knockdown caused mitochondrial fragmentation and loss of membrane potential; yeast and comparative analyses suggest mitochondrial targeting sequences are enriched for NatC-compatible residue patterns.	(damme2016arolefor pages 1-7, nashed2023functionalmappingof pages 1-3, aksnes2023natsata pages 3-4, damme2023expandedinvivo pages 1-2)
Pathway/process: cell survival and proliferation	NAA30 contributes to cell growth and survival.	Knockdown of NAA30 stabilizes p53 and induces apoptosis; in glioblastoma-initiating cells, NAA30 knockdown reduces viability, sphere formation, and hypoxia tolerance.	(grunwald2020divergentarchitectureof pages 1-2, aksnes2023natsata pages 2-3, aksnes2023natsata pages 3-4)
Disease/cancer relevance	NAA30 is increasingly implicated in cancer biology, especially glioblastoma, and NAT dysregulation more broadly is disease-relevant.	NAA30 protein upregulation has been reported in glioblastoma; orthotopic xenograft studies found longer survival in mice receiving NAA30-knockdown glioblastoma cells.	(grunwald2020divergentarchitectureof pages 1-2, aksnes2023natsata pages 2-3)
Key phenotypes of NAA30 loss in human cells	Loss of NAA30 causes distinct cell biological defects rather than a generic collapse of all organelles.	Reported phenotypes include mitochondrial fragmentation, loss of mitochondrial membrane potential, reduced expression of mitochondrial matrix proteins, Golgi fragmentation, reduced cell growth, and apoptosis.	(damme2016arolefor pages 1-7, grunwald2020divergentarchitectureof pages 2-3, aksnes2023natsata pages 3-4)
Key phenotypes in model organisms	NatC deficiency causes conserved organismal and stress phenotypes across species.	Yeast NatC mutants show poor growth on non-fermentable carbon sources and salt/stress sensitivity; Drosophila NatC loss causes reduced longevity, age-dependent motility defects, and male sterility; zebrafish knockout data indicate developmental defects.	(drazic2021humannaa30can pages 1-2, varland2023nterminalacetylationshields pages 1-2, grunwald2020divergentarchitectureof pages 2-3, damme2023expandedinvivo pages 1-2)
Practical interpretation	The best-supported primary function of human NAA30 is co-translational N-terminal acetylation of a methionine-retaining, largely hydrophobic-starting subset of proteins, thereby regulating their stability, targeting, and organelle-related functions.	Particularly strong mechanistic support exists for roles in N-degron shielding, Golgi/vesicle trafficking, cullin neddylation via UBE2M/UBE2F, and mitochondrial integrity.	(damme2016arolefor pages 1-7, varland2023nterminalacetylationshields pages 1-2, varland2023nterminalacetylationshields pages 2-3, aksnes2023natsata pages 3-4)

Table: This table summarizes the main experimentally supported properties of human NAA30 and the NatC complex, including composition, substrate rules, representative substrates, localization, pathways, and loss-of-function phenotypes. It is useful as a compact evidence map for functional annotation.

Conclusions

NAA30 (N-alpha-acetyltransferase 30) functions as the catalytic subunit of the heterotrimeric NatC complex, which catalyzes the co-translational N-terminal acetylation of proteins bearing methionine followed by hydrophobic residues at their N-terminus. This modification, performed at the ribosome, serves multiple critical cellular functions:

Protein quality control: N-terminal acetylation shields hydrophobic N-termini from recognition by the Arg/N-degron pathway, preventing premature protein degradation.
Organelle function: NatC is essential for mitochondrial integrity and function, likely through acetylation of mitochondrial-destined proteins, and plays important roles in Golgi/vesicle trafficking.
Signaling pathways: NatC acetylates key components of the cullin neddylation pathway (UBE2M, UBE2F), affecting ubiquitination networks.
Development and aging: NatC activity is required for normal development across species and contributes to longevity and age-dependent motility.

The evolutionary conservation of NatC from yeast to humans, combined with the diverse phenotypes associated with its loss, underscores the fundamental importance of N-terminal acetylation in eukaryotic cell biology. Recent structural and functional studies have provided unprecedented molecular insights into how NatC recognizes and acetylates specific substrates, and how this modification integrates into cellular protein homeostasis networks. As a potential therapeutic target in cancer and a gene implicated in developmental disorders, NAA30 represents an important focus for future research in both basic biology and translational medicine.

References

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Artifacts

Edison artifact artifact-00

Citations

aksnes2019cotranslationalposttranslationaland pages 1-2
grunwald2020divergentarchitectureof pages 1-2
grunwald2020divergentarchitectureof pages 2-3
aksnes2023natsata pages 2-3
damme2023expandedinvivo pages 1-2
nashed2023functionalmappingof pages 1-3
varland2023nterminalacetylationshields pages 1-2
aksnes2023natsata pages 3-4
keller2024acetyltransferaseincardiovascular pages 1-3
aksnes2023natsata pages 1-2
damme2016arolefor pages 1-7
deng2021molecularmechanismof pages 1-3
deng2021molecularmechanismof pages 3-4
damme2016arolefor pages 10-14
varland2023nterminalacetylationshields pages 2-3
varland2023nterminalacetylationshields pages 3-4
https://doi.org/10.1242/jcs.260766,
https://doi.org/10.1042/bsr20202828,
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https://doi.org/10.1038/s41467-020-19321-8,
https://doi.org/10.1074/mcp.m116.061010,
https://doi.org/10.1016/j.str.2021.05.003,
https://doi.org/10.1016/j.jbc.2022.102824,
https://doi.org/10.1038/s41467-023-42342-y,
https://doi.org/10.1101/2022.08.19.504527,
https://doi.org/10.20517/jca.2024.21,

📚 Additional Documentation

Notes

(NAA30-notes.md)

NAA30 (N-alpha-acetyltransferase 30 / hMak3 / NAT12) research notes

Identity

UniProt Q147X3; HGNC:19844; EC 2.3.1.256. GNAT-fold acetyltransferase, MAK3 subfamily.
CATALYTIC subunit of the human NatC N-terminal acetyltransferase complex (NatC = NAA30 + NAA35 + NAA38, i.e. hMak3/hMak10/hMak31).

Core function

Catalyzes co-translational Nt-acetylation of protein N-terminal methionine residues retained before hydrophobic/bulky residues (Met-Leu, Met-Ile, Met-Phe, Met-Trp, Met-Tyr).
PMID:19398576
NatC associates with ribosomes (cotranslational action). PMID:19398576
Nt-acetylation by NatC shields proteins from degradation. [PMID:37891180 title "N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity"]
ARL8B is an in vivo NatC substrate; NAA30 KD alters hArl8b localization. PMID:19398576
NatC KD -> p53-dependent apoptosis. PMID:19398576

Localization

Cytoplasm (ribosome-associated); also reported nucleus (PMID:25732826, PMID:19398576). Cytosol IDA (HPA).

Annotation notes

IDA + IEA acetyltransferase activity = core MF. Accept GO:0004596 IDA; GO:0120518 (N-terminal-methionine acetyltransferase activity) is the more specific EC-based term, accept.
GO:0016747 (acyltransferase, non-amino-acyl) is a generic GNAT-domain IEA parent — over-annotation relative to the specific Nt-acetyltransferase term.
NatC complex (part_of) well supported by IDA/IPI/IBA.
protein binding IPI annotations all WITH NAA35 (Q5VZE5) — real complex partner; keep non-core (better captured by NatC complex membership).
protein stabilization IDA (PMID:37891180) — downstream BP consequence of Nt-acetylation; keep non-core.

Pn Notes

(NAA30-pn-notes.md)

NAA30 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: Q147X3
AIGR review status: COMPLETE
Review batch: proteostasis-batch-2026-06-07c
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/NAA30/NAA30-ai-review.yaml
AIGR review HTML: present - genes/human/NAA30/NAA30-ai-review.html
Gene notes: present - genes/human/NAA30/NAA30-notes.md
GOA TSV: present - genes/human/NAA30/NAA30-goa.tsv
UniProt record: present - genes/human/NAA30/NAA30-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/NAA30.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/NAA30.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

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

AIGR Review Snapshot

Description: NAA30 (N-alpha-acetyltransferase 30; also hMak3, NAT12) is the catalytic subunit of the human NatC N-terminal acetyltransferase complex (NatC = NAA30 + NAA35 + NAA38). It is a GNAT-fold acetyltransferase (MAK3 subfamily, EC 2.3.1.256) that co-translationally transfers an acetyl group from acetyl-CoA to the alpha-amino group of N-terminal methionine residues retained in front of bulky/hydrophobic residues (Met-Leu, Met-Ile, Met-Phe, Met-Trp, Met-Tyr). NatC associates with ribosomes and acts on nascent polypeptides; this N-terminal acetylation can shield proteins from N-degron-mediated ubiquitination and degradation. NAA30 activity is required for the lysosomal localization of the small GTPase ARL8B (a NatC substrate), and depletion of NatC subunits triggers p53-dependent apoptosis. NAA30 is predominantly cytoplasmic (ribosome-associated) with some reported nuclear localization.
Existing/core annotation action counts: ACCEPT: 14; KEEP_AS_NON_CORE: 6; MARK_AS_OVER_ANNOTATED: 1; NEW: 1

PN Consistency Summary

Consistency: Strong. Deep-research notes, review YAML and PN dossier all agree NAA30 is the catalytic subunit of NatC (=NAA30+NAA35+NAA38, hMak3/hMak10/hMak31), co-translational Nt-acetylation of retained Met before bulky/hydrophobic residues, ribosome-associated. PN-node mapping (NatC complex CC; Nt-acetylation BP) matches the review's MF/CC content. No contradictions.
PN story / NEW pressure: PN projects the BP GO:0006474 (N-terminal protein amino acid acetylation) — verified real and non-obsolete via OLS; confirmed absent from NAA30 GOA (grep). The review captures the MF (GO:0004596, GO:0120518) and CC (GO:0031417) but has no BP for the acetylation process. GO:0006474 is the BP aspect, not a parent of the MF terms, so it is genuinely complementary. Conclusion: ADD GO:0006474 (involved_in) is defensible and would round out MF/BP/CC; not an over-reach for the catalytic subunit.
Evidence alignment: Concordant. PN row carries no reference titles; review/notes anchor to PMID:19398576 (NatC characterization, hMak3 catalytic; IDA GO:0004596/GO:0031417) and PMID:37891180 (Nt-acetylation shields from degradation). Both VERIFIED in the YAML reference_review. No divergence.
Verdict: Consistent and high-quality. Optional ADD of BP GO:0006474 to the review to mirror the PN projection. Recommended edits: Add existing/new BP annotation GO:0006474 (N-terminal protein amino acid acetylation, involved_in) to NAA30 review [YAML].

Full Consistency Review

UniProt: Q147X3 · batch: proteostasis-batch-2026-06-07c · review status: COMPLETE
PN placement: Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide|NatC complex component ; PN-node mapping: subtype mapped→GO:0031417 NatC complex (ok_for_propagation); type mapped→GO:0006474 N-terminal protein amino acid acetylation (ok_for_propagation, new_to_goa)
Consistency: Strong. Deep-research notes, review YAML and PN dossier all agree NAA30 is the catalytic subunit of NatC (=NAA30+NAA35+NAA38, hMak3/hMak10/hMak31), co-translational Nt-acetylation of retained Met before bulky/hydrophobic residues, ribosome-associated. PN-node mapping (NatC complex CC; Nt-acetylation BP) matches the review's MF/CC content. No contradictions.
PN story / NEW pressure: PN projects the BP GO:0006474 (N-terminal protein amino acid acetylation) — verified real and non-obsolete via OLS; confirmed absent from NAA30 GOA (grep). The review captures the MF (GO:0004596, GO:0120518) and CC (GO:0031417) but has no BP for the acetylation process. GO:0006474 is the BP aspect, not a parent of the MF terms, so it is genuinely complementary. Conclusion: ADD GO:0006474 (involved_in) is defensible and would round out MF/BP/CC; not an over-reach for the catalytic subunit.
Mapping strategy: Sound for the catalytic subunit. Subtype→NatC complex (exact CC) and type→Nt-acetylation BP are both appropriate and not too broad (NAA30 directly performs the catalysis). No change to node mapping warranted.
Evidence alignment: Concordant. PN row carries no reference titles; review/notes anchor to PMID:19398576 (NatC characterization, hMak3 catalytic; IDA GO:0004596/GO:0031417) and PMID:37891180 (Nt-acetylation shields from degradation). Both VERIFIED in the YAML reference_review. No divergence.
Verdict: Consistent and high-quality. Optional ADD of BP GO:0006474 to the review to mirror the PN projection. Recommended edits: Add existing/new BP annotation GO:0006474 (N-terminal protein amino acid acetylation, involved_in) to NAA30 review [YAML].
2026-06-18 follow-up: Implemented the YAML edit: added GO:0006474 N-terminal protein amino acid acetylation as a NEW BP recommendation and added it to the catalytic NatC core function.

PN Dossier Context

review_batch: proteostasis-batch-2026-06-07c
review_yaml: genes/human/NAA30/NAA30-ai-review.yaml
PN workbook rows: 1

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

UniProt: Q147X3
In branches: TR
PN-node mapping records (path + ancestors):
- [subtype] Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide|NatC complex component
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0031417 NatC complex]
  rationale: Exact cellular-component match: members are subunits of the NatC N-terminal acetyltransferase complex. Complements the parent BP mapping with the 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.

Projected GO annotations (1)

GO:0006474 N-terminal protein amino acid acetylation | scope=ok_for_propagation_to_go | goa_status=new_to_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.

📄 View Raw YAML

id: Q147X3
gene_symbol: NAA30
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: NAA30 (N-alpha-acetyltransferase 30; also hMak3, NAT12) is the catalytic subunit of the human NatC N-terminal acetyltransferase complex (NatC = NAA30 + NAA35 + NAA38). It is a GNAT-fold acetyltransferase (MAK3 subfamily, EC 2.3.1.256) that co-translationally transfers an acetyl group from acetyl-CoA to the alpha-amino group of N-terminal methionine residues retained in front of bulky/hydrophobic residues (Met-Leu, Met-Ile, Met-Phe, Met-Trp, Met-Tyr). NatC associates with ribosomes and acts on nascent polypeptides; this N-terminal acetylation can shield proteins from N-degron-mediated ubiquitination and degradation. NAA30 activity is required for the lysosomal localization of the small GTPase ARL8B (a NatC substrate), and depletion of NatC subunits triggers p53-dependent apoptosis. NAA30 is predominantly cytoplasmic (ribosome-associated) with some reported nuclear localization.
alternative_products:
- name: '1'
  id: Q147X3-1
- name: '2'
  id: Q147X3-2
  sequence_note: VSP_031581
existing_annotations:
- term:
    id: GO:0031417
    label: NatC complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: NAA30 is a constitutive subunit of the NatC complex. Phylogenetic inference across MAK3 orthologs supports this membership, which is also directly demonstrated experimentally.
    action: ACCEPT
    reason: NatC complex membership is the defining cellular component of NAA30 and is well supported by both phylogenetic and direct experimental evidence.
    supported_by:
    - reference_id: file:human/NAA30/NAA30-uniprot.txt
      supporting_text: Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30.
- term:
    id: GO:0004596
    label: protein-N-terminal amino-acid acetyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro-based electronic annotation of the catalytic N-terminal acetyltransferase activity, consistent with the experimentally demonstrated catalytic activity of NAA30/hMak3.
    action: ACCEPT
    reason: NAA30 is the catalytic subunit of NatC; this MF is its core function and is corroborated by direct experimental (IDA) evidence.
    supported_by:
    - reference_id: file:human/NAA30/NAA30-uniprot.txt
      supporting_text: Catalytic subunit of the N-terminal acetyltransferase C (NatC) complex
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic (UniProt SubCell) annotation of nuclear localization, mirroring the IDA nuclear localization reported by PMID:25732826. NatC predominantly acts in the cytoplasm on ribosomes; nuclear pool is a secondary location.
    action: KEEP_AS_NON_CORE
    reason: Nuclear localization is experimentally reported but secondary to the cytoplasmic ribosome-associated site where NatC performs co-translational N-terminal acetylation.
    supported_by:
    - reference_id: file:human/NAA30/NAA30-uniprot.txt
      supporting_text: Nucleus {ECO:0000269|PubMed:25732826}
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic (UniProt SubCell) annotation of cytoplasmic localization, the primary compartment for NatC co-translational activity.
    action: ACCEPT
    reason: Cytoplasm is the principal, experimentally supported site of NatC action.
    supported_by:
    - reference_id: file:human/NAA30/NAA30-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- 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 GNAT-domain acyltransferase parent term assigned by InterPro. The specific activity of NAA30 is protein N-terminal-methionine acetyltransferase activity, which this term over-generalizes.
    action: MARK_AS_OVER_ANNOTATED
    reason: This is a broad GNAT-fold parent term less precise than the specific N-terminal acetyltransferase activity that is experimentally established for NAA30; the specific terms (GO:0004596 / GO:0120518) already capture the function.
    supported_by:
    - reference_id: file:human/NAA30/NAA30-goa.tsv
      supporting_text: GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups molecular_function ECO:0000256 IEA GO_REF:0000002 InterPro:IPR000182
- term:
    id: GO:0031417
    label: NatC complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: part_of
  review:
    summary: Rule-based (ARBA) electronic annotation of NatC complex membership, redundant with and consistent with stronger IDA/IPI/IBA evidence.
    action: ACCEPT
    reason: Correct and well-corroborated NatC complex membership.
    supported_by:
    - reference_id: file:human/NAA30/NAA30-uniprot.txt
      supporting_text: Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30.
- term:
    id: GO:0120518
    label: protein N-terminal-methionine acetyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: EC 2.3.1.256-based annotation of the specific N-terminal-methionine acetyltransferase activity. This is the most precise molecular-function term for NAA30's catalytic activity (acetylation of retained N-terminal Met). NatC substrate specificity is distinct from NatA and NatB, since NatC acetylates proteins that retain the initiator methionine followed by hydrophobic/amphipathic residues (canonical Met-Leu, Met-Ile, Met-Phe, Met-Trp), the defining substrate class for this MF term.
    action: ACCEPT
    reason: Most specific and accurate MF for the catalytic subunit; matches the documented EC number and Rhea reactions for NatC-mediated Met-N-terminal acetylation.
    supported_by:
    - reference_id: file:human/NAA30/NAA30-goa.tsv
      supporting_text: GO:0120518 protein N-terminal-methionine acetyltransferase activity molecular_function ECO:0000501 IEA GO_REF:0000120
    - reference_id: file:human/NAA30/NAA30-deep-research-falcon.md
      supporting_text: NatC acetylates proteins that retain the initiator methionine followed by hydrophobic or amphipathic residues
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19398576
  qualifier: enables
  review:
    summary: IntAct interaction with NAA35 (Q5VZE5), the NatC auxiliary subunit. The bare protein binding term is uninformative; the relevant interaction is NatC complex assembly.
    action: KEEP_AS_NON_CORE
    reason: Records a genuine intra-complex interaction with the NAA35 auxiliary subunit, but the uninformative GO:0005515 term is non-core; NatC complex membership captures the meaningful content.
    supported_by:
    - reference_id: file:human/NAA30/NAA30-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19398576 UniProtKB:Q5VZE5
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: BioPlex interactome interaction with NAA35 (Q5VZE5). Uninformative bare protein binding term reflecting NatC complex assembly.
    action: KEEP_AS_NON_CORE
    reason: Real interaction with the NAA35 auxiliary subunit; non-core as a bare protein binding annotation, subsumed by the NatC complex term.
    supported_by:
    - reference_id: file:human/NAA30/NAA30-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:33961781 UniProtKB:Q5VZE5
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Multimodal cell-maps interactome interaction with NAA35 (Q5VZE5). Uninformative bare protein binding term reflecting NatC complex assembly.
    action: KEEP_AS_NON_CORE
    reason: Real interaction with the NAA35 auxiliary subunit; non-core as a bare protein binding annotation, subsumed by the NatC complex term.
    supported_by:
    - reference_id: file:human/NAA30/NAA30-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:40205054 UniProtKB:Q5VZE5
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Direct immunofluorescence (HPA) evidence for cytosolic localization, consistent with the principal site of NatC action.
    action: ACCEPT
    reason: IDA-supported cytosolic localization matching the cytoplasmic ribosome-associated site of NatC.
    supported_by:
    - reference_id: file:human/NAA30/NAA30-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component ECO:0000314 IDA GO_REF:0000052
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: NAS
  original_reference_id: PMID:19398576
  qualifier: located_in
  review:
    summary: Non-traceable author statement (ComplexPortal) of cytoplasmic localization, consistent with the experimentally documented cytoplasmic site of NatC.
    action: ACCEPT
    reason: Consistent with the primary cytoplasmic localization of NatC; corroborated by IDA evidence.
    supported_by:
    - reference_id: file:human/NAA30/NAA30-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0031417
    label: NatC complex
  evidence_type: IPI
  original_reference_id: PMID:19398576
  qualifier: part_of
  review:
    summary: ComplexPortal/IPI evidence that NAA30 is part of the NatC complex, from the study that identified the human NatC complex.
    action: ACCEPT
    reason: Direct experimental support for NatC complex membership.
    supported_by:
    - reference_id: PMID:19398576
      supporting_text: the catalytic subunit hMak3 and the auxiliary subunits hMak10 and hMak31
- term:
    id: GO:0004596
    label: protein-N-terminal amino-acid acetyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:37891180
  qualifier: enables
  review:
    summary: Direct experimental evidence for NAA30's N-terminal acetyltransferase activity in the study showing NatC-mediated N-terminal acetylation shields proteins from degradation. NAA30 contains the catalytic GNAT fold and transfers an acetyl group from acetyl-CoA to the free alpha-amino group at the substrate N-terminus.
    action: ACCEPT
    reason: Core catalytic molecular function of NAA30, directly demonstrated.
    supported_by:
    - reference_id: file:human/NAA30/NAA30-uniprot.txt
      supporting_text: Catalyzes acetylation of the N-terminal methionine residues of peptides beginning with Met-Leu-Ala and Met-Leu-Gly
    - reference_id: file:human/NAA30/NAA30-deep-research-falcon.md
      supporting_text: NAA30 catalyzes the irreversible transfer of an acetyl group from acetyl coenzyme A (acetyl-CoA) to the free α-amino group at the N-terminus of nascent protein chains
- term:
    id: GO:0031417
    label: NatC complex
  evidence_type: IDA
  original_reference_id: PMID:37891180
  qualifier: part_of
  review:
    summary: Direct experimental confirmation of NatC complex membership in the protein-shielding/longevity study.
    action: ACCEPT
    reason: Well-supported NatC complex membership.
    supported_by:
    - reference_id: file:human/NAA30/NAA30-uniprot.txt
      supporting_text: Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30.
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: IDA
  original_reference_id: PMID:37891180
  qualifier: involved_in
  review:
    summary: NatC-mediated N-terminal acetylation shields substrate proteins from N-degron-mediated degradation, thereby stabilizing them. Mechanistically, unacetylated Met-hydrophobic N-termini are recognized as N-degrons by the Arg/N-degron pathway E3 ligases (UBR1, UBR2, UBR4-KCMF1); NatC acetylation masks these N-termini. This is a downstream biological-process consequence of NAA30's catalytic activity.
    action: KEEP_AS_NON_CORE
    reason: Protein stabilization is a real and experimentally supported outcome of NatC N-terminal acetylation, but it is a downstream process rather than NAA30's direct molecular function (the catalytic acetyltransferase activity is core).
    supported_by:
    - reference_id: file:human/NAA30/NAA30-uniprot.txt
      supporting_text: N- terminal acetylation protects proteins from ubiquitination and degradation by the N-end rule pathway
    - reference_id: file:human/NAA30/NAA30-deep-research-falcon.md
      supporting_text: N-terminal acetylation by NatC shields these hydrophobic N-termini from recognition by the degradation machinery
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:25732826
  qualifier: located_in
  review:
    summary: Direct experimental evidence for a nuclear pool of NAA30. NatC predominantly acts cotranslationally in the cytoplasm; the nuclear localization is secondary.
    action: KEEP_AS_NON_CORE
    reason: Experimentally observed nuclear localization, but secondary to the cytoplasmic ribosome-associated site of NatC function.
    supported_by:
    - reference_id: file:human/NAA30/NAA30-uniprot.txt
      supporting_text: Nucleus {ECO:0000269|PubMed:25732826}
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:25732826
  qualifier: located_in
  review:
    summary: Direct experimental evidence for cytoplasmic localization of NAA30, the primary site of NatC action.
    action: ACCEPT
    reason: Cytoplasm is the principal, experimentally supported compartment of NatC.
    supported_by:
    - reference_id: file:human/NAA30/NAA30-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0004596
    label: protein-N-terminal amino-acid acetyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:19398576
  qualifier: enables
  review:
    summary: Direct in vitro demonstration that hMak3/NAA30 acetylates Met-Leu protein N-termini, establishing its catalytic N-terminal acetyltransferase activity.
    action: ACCEPT
    reason: Core catalytic molecular function of NAA30, directly demonstrated in vitro.
    supported_by:
    - reference_id: PMID:19398576
      supporting_text: hMak3 acetylates Met-Leu protein N termini in vitro
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:19398576
  qualifier: located_in
  review:
    summary: Direct experimental cytoplasmic localization of NAA30, consistent with ribosome-associated NatC activity. NatC functions co-translationally at the ribosome, positioned to acetylate nascent chains as they emerge from the exit tunnel.
    action: ACCEPT
    reason: Cytoplasm is the principal experimentally supported compartment of NatC.
    supported_by:
    - reference_id: PMID:19398576
      supporting_text: This complex associates with ribosomes
    - reference_id: file:human/NAA30/NAA30-deep-research-falcon.md
      supporting_text: Human NatC subunits co-sediment with ribosomes, and structural studies identified a ribosome-binding patch in the elongated tip region of the NatC complex
- term:
    id: GO:0031417
    label: NatC complex
  evidence_type: IDA
  original_reference_id: PMID:19398576
  qualifier: part_of
  review:
    summary: Direct experimental identification of NAA30 (hMak3) as the catalytic subunit of the human NatC complex.
    action: ACCEPT
    reason: Defining cellular component, directly demonstrated.
    supported_by:
    - reference_id: PMID:19398576
      supporting_text: the catalytic subunit hMak3 and the auxiliary subunits hMak10 and hMak31
- term:
    id: GO:0006474
    label: N-terminal protein amino acid acetylation
  evidence_type: IDA
  original_reference_id: PMID:19398576
  qualifier: involved_in
  review:
    summary: NAA30/hMak3 is the catalytic subunit of human NatC, which performs cotranslational N-terminal acetylation of protein substrates.
    action: NEW
    reason: PN correctly flagged that the review captures the NatC MF and CC but lacks the complementary BP term for the acetylation process itself. This is appropriate for the catalytic subunit.
    supported_by:
    - reference_id: PMID:19398576
      supporting_text: hMak3 acetylates Met-Leu protein N termini in vitro
      reference_section_type: ABSTRACT
    - reference_id: PMID:19398576
      supporting_text: the human NatC complex functions in cotranslational N-terminal acetylation
      reference_section_type: ABSTRACT
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/Swiss-Prot Subcellular Location vocabulary mapping
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:19398576
  title: Knockdown of human N alpha-terminal acetyltransferase complex C leads to p53-dependent apoptosis and aberrant human Arl8b localization.
  findings:
  - statement: The human NatC complex contains the catalytic subunit hMak3 (NAA30) and auxiliary subunits hMak10 (NAA35) and hMak31 (NAA38); it associates with ribosomes and hMak3 acetylates Met-Leu protein N-termini in vitro.
    reference_section_type: ABSTRACT
  - statement: Knockdown of NatC subunits results in p53-dependent cell death and aberrant ARL8B localization, indicating ARL8B is a NatC substrate in vivo.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached publication title matches the YAML title; GOA anchors this PMID to IDA for GO:0004596 (N-terminal acetyltransferase activity) and GO:0031417 (NatC complex). This is the NatC complex-characterization paper establishing NAA30 (hMak3) as the catalytic subunit, the gene's core function.
- id: PMID:25732826
  title: An organellar nα-acetyltransferase, naa60, acetylates cytosolic N termini of transmembrane proteins and maintains Golgi integrity.
  findings:
  - statement: Reports cytoplasmic and nuclear localization data for NAA30 alongside characterization of the Golgi-associated NAT NAA60.
    reference_section_type: RESULTS
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:37891180
  title: N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity.
  findings:
  - statement: NatC-mediated N-terminal acetylation shields substrate proteins from N-degron-dependent ubiquitination and degradation, promoting protein stabilization, motility and longevity.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached publication title matches the YAML title; GOA anchors this PMID to IDA for GO:0004596, GO:0031417 (NatC complex) and GO:0050821 (protein stabilization). Establishes the in vivo biological consequence of NatC/NAA30 N-terminal acetylation.
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: file:human/NAA30/NAA30-deep-research-falcon.md
  title: Falcon deep research report for NAA30
  findings:
  - statement: NAA30 is the catalytic GNAT-fold subunit of the heterotrimeric NatC complex (NAA30 catalytic, NAA35 large auxiliary/ribosome-anchoring, NAA38 small auxiliary) that co-translationally acetylates the alpha-amino group of N-terminal methionines retained in front of hydrophobic/amphipathic residues (Met-Leu, Met-Ile, Met-Phe, Met-Trp).
    reference_section_type: OTHER
  - statement: NatC-mediated N-terminal acetylation shields hydrophobic Met-starting N-termini from recognition as N-degrons by the Arg/N-degron pathway E3 ligases (UBR1, UBR2, UBR4-KCMF1), protecting substrates from proteasomal degradation; validated human NatC substrates include the trafficking GTPase ARL8B.
    reference_section_type: OTHER
  reference_review:
    relevance: HIGH
    correctness: UNVERIFIED
    review_notes: LLM-synthesized (Edison/Falcon) deep-research report; not independently verified against primary full text and treated as UNVERIFIED. NAA30-catalytic-specific claims used here (GNAT-fold acetyl-CoA-dependent transfer to the N-terminal alpha-amino group; NatC Met-hydrophobic substrate class distinct from NatA/NatB; ribosome co-sedimentation; N-degron shielding) are consistent with the cached primary literature (PMID:19398576, PMID:37891180) and with UniProt. The report also generalizes across the NatC complex and other NATs and attributes some functions to auxiliary subunits (e.g. NAA35 as ribosome anchor, NAA38 broadening substrate specificity/thermostability) and to broader NatC biology (mitochondrial integrity, Golgi/vesicle trafficking, cullin neddylation via UBE2M/UBE2F, cancer/development) - these are complex-level or pathway-level claims and were NOT used to assert new NAA30-specific catalytic molecular functions.
core_functions:
- description: Catalytic subunit of the NatC N-terminal acetyltransferase complex that transfers acetyl groups from acetyl-CoA to the alpha-amino group of N-terminal methionine residues retained in front of bulky/hydrophobic residues (Met-Leu, Met-Ile, Met-Phe, Met-Trp, Met-Tyr), acting co-translationally on ribosome-bound nascent chains.
  molecular_function:
    id: GO:0120518
    label: protein N-terminal-methionine acetyltransferase activity
  in_complex:
    id: GO:0031417
    label: NatC complex
  directly_involved_in:
  - id: GO:0006474
    label: N-terminal protein amino acid acetylation
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: file:human/NAA30/NAA30-uniprot.txt
    supporting_text: Catalytic subunit of the N-terminal acetyltransferase C (NatC) complex
  - reference_id: PMID:19398576
    supporting_text: hMak3 acetylates Met-Leu protein N termini in vitro
proposed_new_terms: []
suggested_questions:
- question: What is the full repertoire of human NatC substrates (Met-hydrophobic N-termini), and how much overlap exists with NatE/NAA50 specificity?
- question: Is the nuclear pool of NAA30 catalytically active on a distinct substrate set, or does it reflect mislocalization/relocalization independent of NatC function?
suggested_experiments:
- description: Quantitative N-terminomics of NAA30-knockout versus wild-type human cells to define the NatC-dependent N-terminal acetylome.
- description: Reconstituted in vitro acetylation assays with recombinant NatC (NAA30/NAA35/NAA38) on a panel of Met-X peptides to quantify substrate specificity and the contribution of each auxiliary subunit.
- description: Degradation/stability assays (e.g. cycloheximide chase, tandem fluorescent timer reporters) on defined NatC substrates in NAA30-depleted cells to test the N-degron-shielding model in human cells.

NAA30

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Comprehensive Research Report: Human NAA30 (N-alpha-acetyltransferase 30)

Gene Identity and Overview

Primary Catalytic Function and Reaction Mechanism

Enzymatic Activity

The NatC Complex Composition and Structure

Substrate Specificity

N-Terminal Sequence Recognition

Substrate Coverage and Identified Targets

Subcellular Localization

Biological Processes and Biochemical Pathways

Protein Quality Control and the Arg/N-Degron Pathway

Cullin Neddylation

Mitochondrial Function and Integrity

Golgi and Vesicle Trafficking

Cell Proliferation, Survival, and Development

Stress Responses and Aging

Disease Relevance

Summary of Key Findings

Conclusions

Artifacts

Citations

📚 Additional Documentation

Notes

NAA30 (N-alpha-acetyltransferase 30 / hMak3 / NAT12) research notes

Identity

Core function

Localization

Annotation notes

Pn Notes

NAA30 PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

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

Projected GO annotations (1)

Note

📄 View Raw YAML