id: Q14CX7 gene_symbol: NAA25 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: NAA25 (N-alpha-acetyltransferase 25; also MDM20, NAP1, p120) is the large non-catalytic auxiliary subunit of the human NatB N-terminal acetyltransferase complex. NatB is composed of the catalytic subunit NAA20 and the auxiliary subunit NAA25, and it co-translationally acetylates the alpha-amino group of N-terminal methionine residues that are retained in front of acidic or amide side chains (Met-Asp, Met-Glu, Met-Asn and Met-Gln N-termini). NAA25 is a TPR-repeat/alpha-solenoid protein that cradles and stabilizes the catalytic NAA20 subunit and anchors the complex to ribosomes, positioning it to act on nascent polypeptides. It is a cytoplasmic protein and is required for normal cell-cycle progression. Loss of NatB activity (e.g. NAA20 variants) is associated with neurodevelopmental disease, underscoring the physiological importance of NatB-mediated N-terminal acetylation. alternative_products: - name: '1' id: Q14CX7-1 - name: '2' id: Q14CX7-2 sequence_note: VSP_026629, VSP_026630 existing_annotations: - term: id: GO:0007010 label: cytoskeleton organization evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: Phylogenetically inferred from NatB orthologs (yeast/fly), where NatB-mediated N-terminal acetylation of actin and tropomyosin affects actin cytoskeleton and tropomyosin function. For human NAA25 this is a downstream biological-process consequence of NatB substrate acetylation, not a direct molecular activity of the auxiliary subunit. action: KEEP_AS_NON_CORE reason: Plausible process annotation inherited by phylogenetic transfer from NatB orthologs whose substrates (tropomyosin/actin) link N-terminal acetylation to the cytoskeleton; it is indirect and peripheral to NAA25's core complex/scaffold role. supported_by: - reference_id: file:human/NAA25/NAA25-goa.tsv supporting_text: GO:0007010 cytoskeleton organization biological_process ECO:0000318 IBA - term: id: GO:0010698 label: acetyltransferase activator activity evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables review: summary: NAA25 is the non-catalytic auxiliary subunit of NatB that binds and activates/scaffolds the catalytic subunit NAA20. Acetyltransferase activator activity is the appropriate molecular function for this auxiliary role, since NAA25 itself does not catalyze acetyl transfer but is required for full NatB activity. action: ACCEPT reason: This term correctly captures NAA25's core non-catalytic function as the activating/scaffolding subunit of the NatB acetyltransferase, consistent with the requirement of NAA25 for the NatB complex to display N-terminal acetyltransferase activity. supported_by: - reference_id: PMID:18570629 supporting_text: They form a stable complex and in vitro display sequence-specific N(alpha)-acetyltransferase activity on a peptide with the N-terminus Met-Asp-. - reference_id: file:human/NAA25/NAA25-uniprot.txt supporting_text: Non-catalytic subunit of the NatB complex which catalyzes acetylation of the N-terminal methionine residues of peptides beginning with Met-Asp, Met-Glu, Met-Asn and Met-Gln. - term: id: GO:0031416 label: NatB complex evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of review: summary: NAA25 is a constitutive component of the NatB N-terminal acetyltransferase complex (NAA20 + NAA25). This is the core cellular component for the gene. action: ACCEPT reason: Membership in the NatB complex is established experimentally (co-purification, cryo-EM) and by phylogenetic inference; it is the defining cellular component of NAA25. supported_by: - reference_id: file:human/NAA25/NAA25-uniprot.txt supporting_text: Component of the N-terminal acetyltransferase B (NatB) complex which is composed of NAA20 and NAA25. - term: id: GO:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: Electronic annotation of cytoplasmic localization, consistent with the experimentally documented cytoplasmic location of NatB. action: ACCEPT reason: Correct compartment for this cytoplasmic, ribosome-associated complex subunit; agrees with experimental IDA evidence. supported_by: - reference_id: file:human/NAA25/NAA25-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18570629 qualifier: enables review: summary: IntAct-derived interaction with NAA20 (P61599), the catalytic NatB subunit. The bare protein binding term is uninformative; the biologically meaningful interaction is assembly of the NatB complex, already captured by the NatB complex annotation. action: KEEP_AS_NON_CORE reason: Records a real, functionally relevant interaction (with the catalytic subunit NAA20) but the uninformative GO:0005515 term is not core; the informative content is the NatB complex membership. supported_by: - reference_id: file:human/NAA25/NAA25-goa.tsv supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:18570629 UniProtKB:P61599 - 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 NAA25's role in the cytoplasmic NatB complex. action: ACCEPT reason: IDA-supported cytosolic localization agrees with the documented cytoplasmic site of action of NatB. supported_by: - reference_id: file:human/NAA25/NAA25-goa.tsv supporting_text: GO:0005829 cytosol cellular_component ECO:0000314 IDA GO_REF:0000052 - term: id: GO:0005737 label: cytoplasm evidence_type: IDA original_reference_id: PMID:18570629 qualifier: located_in review: summary: Direct experimental evidence (ComplexPortal, from the hNatB identification study) for cytoplasmic localization of the NatB complex. action: ACCEPT reason: Experimentally supported cytoplasmic localization consistent with co-translational action on ribosomes. supported_by: - reference_id: file:human/NAA25/NAA25-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm' - term: id: GO:0031416 label: NatB complex evidence_type: IPI original_reference_id: PMID:18570629 qualifier: part_of review: summary: ComplexPortal/IPI evidence that NAA25 is part of the NatB complex, from the study that identified the human NatB complex. action: ACCEPT reason: Direct experimental support for NatB complex membership; the defining cellular component of NAA25. supported_by: - reference_id: PMID:18570629 supporting_text: They form a stable complex and in vitro display sequence-specific N(alpha)-acetyltransferase activity on a peptide with the N-terminus Met-Asp-. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:34230638 qualifier: enables review: summary: Interaction with NAA20 (P61599) documented in the study of disease-causing NAA20 variants. The bare protein binding term is uninformative; the interaction reflects NatB complex assembly. action: KEEP_AS_NON_CORE reason: Real interaction with the catalytic NatB subunit but uninformative as a GO:0005515 annotation; the NatB complex membership term captures the meaningful content. supported_by: - reference_id: file:human/NAA25/NAA25-goa.tsv supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:34230638 UniProtKB:P61599 references: - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000052 title: Gene Ontology annotation based on curation of immunofluorescence data findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:18570629 title: 'Identification of the human N(alpha)-acetyltransferase complex B (hNatB): a complex important for cell-cycle progression.' findings: - statement: The human NatB complex consists of the catalytic subunit hNAT3 (NAA20) and the auxiliary subunit hMDM20 (NAA25); they form a stable complex with sequence-specific N-terminal acetyltransferase activity on Met-Asp- N-termini. reference_section_type: ABSTRACT - statement: hNAT3 and hMDM20 co-sediment with ribosomal pellets, supporting co-translational action of NatB on nascent polypeptides. reference_section_type: ABSTRACT - statement: Knockdown of hMDM20 (NAA25) disrupts normal cell-cycle progression and inhibits growth of HeLa cells. reference_section_type: ABSTRACT reference_review: relevance: HIGH correctness: VERIFIED review_notes: Cached publication title matches the YAML title; GOA also anchors this PMID to IPI for GO:0031416 (NatB complex). This is the NatB complex-characterization paper establishing NAA25 (hMDM20) as the auxiliary subunit partnering NAA20, the gene's core function. - id: PMID:34230638 title: Missense NAA20 variants impairing the NatB protein N-terminal acetyltransferase cause autosomal recessive developmental delay, intellectual disability, and microcephaly. findings: - statement: NatB is composed of NAA20 and NAA25; impairment of NatB N-terminal acetyltransferase activity by NAA20 variants causes a recessive neurodevelopmental disorder, underscoring the physiological importance of NatB. reference_section_type: ABSTRACT reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Cached publication title matches the YAML title; concerns disease variants in the catalytic subunit NAA20 (not NAA25 itself) but establishes the physiological importance of the NatB complex of which NAA25 is the auxiliary subunit. Supporting/contextual for NAA25. core_functions: - description: Non-catalytic auxiliary subunit of the NatB N-terminal acetyltransferase complex that binds, activates and scaffolds the catalytic subunit NAA20, enabling co-translational N-terminal acetylation of Met-Asp/Met-Glu/Met-Asn/Met-Gln protein N-termini. molecular_function: id: GO:0010698 label: acetyltransferase activator activity in_complex: id: GO:0031416 label: NatB complex locations: - id: GO:0005737 label: cytoplasm supported_by: - reference_id: file:human/NAA25/NAA25-uniprot.txt supporting_text: Non-catalytic subunit of the NatB complex which catalyzes acetylation of the N-terminal methionine residues of peptides beginning with Met-Asp, Met-Glu, Met-Asn and Met-Gln. - reference_id: PMID:18570629 supporting_text: They form a stable complex and in vitro display sequence-specific N(alpha)-acetyltransferase activity on a peptide with the N-terminus Met-Asp-. proposed_new_terms: [] suggested_questions: - question: Does the NAA25 alpha-solenoid scaffold contribute to ribosome anchoring of NatB independently of NAA20, and which surface mediates ribosome binding? - question: Are there human NAA25 (as opposed to NAA20) loss-of-function variants, and do they phenocopy the NAA20-associated neurodevelopmental disorder? suggested_experiments: - description: Cryo-EM of the NatB-ribosome-nascent chain complex to define how NAA25 positions the catalytic NAA20 subunit at the ribosomal exit tunnel. - description: Separation-of-function mutagenesis of the NAA25 TPR/solenoid surfaces to dissect NAA20-binding (activation) from ribosome-anchoring, assayed by in vitro N-terminal acetylation and ribosome co-sedimentation. - description: N-terminomics (e.g. SILAC-based COFRADIC) of NAA25-depleted human cells to map the NatB substrate repertoire whose N-terminal acetylation depends on the auxiliary subunit.