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.