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.
| 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 Ξ±-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 nΞ±-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 nΞ±-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 |
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Download this section (compressed HTML)Q: What is the full repertoire of human NatC substrates (Met-hydrophobic N-termini), and how much overlap exists with NatE/NAA50 specificity?
Q: Is the nuclear pool of NAA30 catalytically active on a distinct substrate set, or does it reflect mislocalization/relocalization independent of NatC function?
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.
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