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.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0007010 cytoskeleton organization | IBA GO_REF:0000033 | KEEP AS NON CORE | 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. 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. Supporting Evidence: file:human/NAA25/NAA25-goa.tsv GO:0007010 cytoskeleton organization biological_process ECO:0000318 IBA |
| GO:0010698 acetyltransferase activator activity | IBA GO_REF:0000033 | ACCEPT | 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. 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. Supporting Evidence: PMID:18570629 They form a stable complex and in vitro display sequence-specific N(alpha)-acetyltransferase activity on a peptide with the N-terminus Met-Asp-. file:human/NAA25/NAA25-uniprot.txt 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. |
| GO:0031416 NatB complex | IBA GO_REF:0000033 | ACCEPT | Summary: NAA25 is a constitutive component of the NatB N-terminal acetyltransferase complex (NAA20 + NAA25). This is the core cellular component for the gene. 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. Supporting Evidence: file:human/NAA25/NAA25-uniprot.txt Component of the N-terminal acetyltransferase B (NatB) complex which is composed of NAA20 and NAA25. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation of cytoplasmic localization, consistent with the experimentally documented cytoplasmic location of NatB. Reason: Correct compartment for this cytoplasmic, ribosome-associated complex subunit; agrees with experimental IDA evidence. Supporting Evidence: file:human/NAA25/NAA25-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005515 protein binding | IPI PMID:18570629 Identification of the human N(alpha)-acetyltransferase compl... | KEEP AS NON CORE | 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. 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. Supporting Evidence: file:human/NAA25/NAA25-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:18570629 UniProtKB:P61599 |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Direct immunofluorescence (HPA) evidence for cytosolic localization, consistent with NAA25's role in the cytoplasmic NatB complex. Reason: IDA-supported cytosolic localization agrees with the documented cytoplasmic site of action of NatB. Supporting Evidence: file:human/NAA25/NAA25-goa.tsv GO:0005829 cytosol cellular_component ECO:0000314 IDA GO_REF:0000052 |
| GO:0005737 cytoplasm | IDA PMID:18570629 Identification of the human N(alpha)-acetyltransferase compl... | ACCEPT | Summary: Direct experimental evidence (ComplexPortal, from the hNatB identification study) for cytoplasmic localization of the NatB complex. Reason: Experimentally supported cytoplasmic localization consistent with co-translational action on ribosomes. Supporting Evidence: file:human/NAA25/NAA25-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0031416 NatB complex | IPI PMID:18570629 Identification of the human N(alpha)-acetyltransferase compl... | ACCEPT | Summary: ComplexPortal/IPI evidence that NAA25 is part of the NatB complex, from the study that identified the human NatB complex. Reason: Direct experimental support for NatB complex membership; the defining cellular component of NAA25. Supporting Evidence: PMID:18570629 They form a stable complex and in vitro display sequence-specific N(alpha)-acetyltransferase activity on a peptide with the N-terminus Met-Asp-. |
| GO:0005515 protein binding | IPI PMID:34230638 Missense NAA20 variants impairing the NatB protein N-termina... | KEEP AS NON CORE | 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. Reason: Real interaction with the catalytic NatB subunit but uninformative as a GO:0005515 annotation; the NatB complex membership term captures the meaningful content. Supporting Evidence: file:human/NAA25/NAA25-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:34230638 UniProtKB:P61599 |
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Download this section (compressed HTML)Q: Does the NAA25 alpha-solenoid scaffold contribute to ribosome anchoring of NatB independently of NAA20, and which surface mediates ribosome binding?
Q: Are there human NAA25 (as opposed to NAA20) loss-of-function variants, and do they phenocopy the NAA20-associated neurodevelopmental disorder?
Experiment: Cryo-EM of the NatB-ribosome-nascent chain complex to define how NAA25 positions the catalytic NAA20 subunit at the ribosomal exit tunnel.
Experiment: 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.
Experiment: 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.
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