NAA35 (N-alpha-acetyltransferase 35; also MAK10, EGAP) is the large non-catalytic auxiliary/scaffold subunit of the human NatC N-terminal acetyltransferase complex (NatC = NAA30 catalytic + NAA35 + NAA38). It does not itself catalyze acetyl transfer; instead it scaffolds the complex and is required for NatC function and integrity. NatC co-translationally acetylates the alpha-amino group of N-terminal methionine residues retained in front of bulky/hydrophobic residues, a modification that shields substrates from N-degron-mediated ubiquitination and degradation. NAA35 is predominantly cytoplasmic and ribosome-associated. Loss of NatC subunits triggers p53-dependent apoptosis, and the mouse ortholog (EGAP) has been linked to smooth-muscle-cell proliferation and embryonic vascular development.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0031417 NatC complex | IBA GO_REF:0000033 | ACCEPT | Summary: NAA35 is a constitutive auxiliary subunit of the NatC complex; phylogenetic inference across MAK10 orthologs supports this membership, which is also directly demonstrated. Structural work (Grunwald 2020) shows NAA35 is the central scaffold that wraps around both NAA30 and NAA38 to hold the heterotrimer together. Reason: NatC complex membership is the defining cellular component of NAA35 and is well supported by phylogenetic and direct experimental evidence. Supporting Evidence: file:human/NAA35/NAA35-uniprot.txt Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30. file:human/NAA35/NAA35-deep-research-falcon.md NAA35's primary role is to serve as the central assembly scaffold that organizes the NatC complex architecture and mediates its interaction with ribosomes, thereby enabling co-translational N-terminal acetylation of specific substrate proteins |
| GO:0043066 negative regulation of apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Knockdown of NatC subunits (including NAA35) induces p53-dependent apoptosis, implying that NatC activity normally suppresses apoptosis. This is a downstream biological-process consequence of NatC-mediated N-terminal acetylation, not a direct molecular activity of NAA35. Reason: Plausible process annotation derived from the apoptotic phenotype of NatC depletion; indirect and downstream of the complex's core acetyltransferase activity. Supporting Evidence: file:human/NAA35/NAA35-uniprot.txt Involved in regulation of apoptosis and proliferation of smooth muscle cells |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation of cytoplasmic localization, consistent with the experimentally documented cytoplasmic site of NatC. Reason: Cytoplasm is the principal, experimentally supported compartment of NatC. Supporting Evidence: file:human/NAA35/NAA35-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0031417 NatC complex | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based electronic annotation of NatC complex membership, redundant with and consistent with stronger experimental evidence. Reason: Correct and well-corroborated NatC complex membership. Supporting Evidence: file:human/NAA35/NAA35-uniprot.txt Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30. |
| GO:0005515 protein binding | IPI PMID:19398576 Knockdown of human N alpha-terminal acetyltransferase comple... | KEEP AS NON CORE | Summary: IntAct interactions with NAA30 (Q147X3) and NAA38 (Q9BRA0), the other NatC subunits. The bare protein binding term is uninformative; the relevant interaction is NatC complex assembly. Reason: Records genuine intra-complex interactions but the uninformative GO:0005515 term is non-core; NatC complex membership captures the meaningful content. Supporting Evidence: file:human/NAA35/NAA35-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19398576 UniProtKB:Q147X3 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Binary yeast two-hybrid interactome (HuRI) interaction with TRIM7 (Q9C029), an E3 ligase unrelated to NatC function. An isolated high-throughput interaction that does not inform NAA35's core role. Reason: Bare protein binding from a single high-throughput binary screen with a partner (TRIM7) outside the NatC complex; uninformative and not part of the core function. Supporting Evidence: file:human/NAA35/NAA35-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32296183 UniProtKB:Q9C029 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex interactome interactions with NAA30 (Q147X3) and NAA38 (Q9BRA0). Uninformative bare protein binding term reflecting NatC complex assembly. Reason: Real interactions with the other NatC subunits; non-core as a bare protein binding annotation, subsumed by the NatC complex term. Supporting Evidence: file:human/NAA35/NAA35-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:33961781 UniProtKB:Q147X3 |
| 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 NAA30 (Q147X3). Uninformative bare protein binding term reflecting NatC complex assembly. Reason: Real interaction with the NAA30 catalytic subunit; non-core as a bare protein binding annotation, subsumed by the NatC complex term. Supporting Evidence: file:human/NAA35/NAA35-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:40205054 UniProtKB:Q147X3 |
| GO:0048659 smooth muscle cell proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic annotation transferred from the mouse ortholog (EGAP), which was implicated in smooth-muscle-cell proliferation and embryonic vascular development. This is a peripheral, organism-specific developmental role. Reason: Transferred from mouse phenotype data; peripheral to NAA35's core NatC scaffold function and not a direct molecular activity. Supporting Evidence: file:human/NAA35/NAA35-uniprot.txt Involved in regulation of apoptosis and proliferation of smooth muscle cells |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Direct immunofluorescence (HPA) evidence for cytosolic localization, consistent with the cytoplasmic site of NatC. Reason: IDA-supported cytosolic localization matching the cytoplasmic ribosome-associated site of NatC. Supporting Evidence: file:human/NAA35/NAA35-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 documented cytoplasmic site of NatC. Reason: Consistent with the primary cytoplasmic localization of NatC. Supporting Evidence: file:human/NAA35/NAA35-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 NAA35 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: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/NAA35/NAA35-uniprot.txt Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30. |
| GO:0005737 cytoplasm | IDA PMID:19398576 Knockdown of human N alpha-terminal acetyltransferase comple... | ACCEPT | Summary: Direct experimental cytoplasmic localization of NAA35, consistent with ribosome-associated NatC activity. NAA35 in particular carries the principal ribosome-binding surface of NatC (an electropositive C-terminal tip region), so its cytoplasmic localization reflects co-translational action at the ribosome. Reason: Cytoplasm is the principal experimentally supported compartment of NatC. Supporting Evidence: PMID:19398576 This complex associates with ribosomes file:human/NAA35/NAA35-deep-research-falcon.md NAA35, as part of the NatC complex, localizes to ribosomes where it functions co-translationally |
| GO:0031417 NatC complex | IDA PMID:19398576 Knockdown of human N alpha-terminal acetyltransferase comple... | ACCEPT | Summary: Direct experimental identification of NAA35 (hMak10) as an auxiliary 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:0043066 negative regulation of apoptotic process | IMP PMID:19398576 Knockdown of human N alpha-terminal acetyltransferase comple... | KEEP AS NON CORE | Summary: Mutant-phenotype evidence that NAA35 (hMak10) knockdown induces p53-dependent apoptosis, indicating NatC normally suppresses apoptosis. Downstream consequence of complex function. Reason: Real phenotype-based process annotation, but indirect and downstream of NatC's core acetyltransferase activity. Supporting Evidence: PMID:19398576 results in p53-dependent cell death |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity-based annotation of cytoplasmic localization (from mouse ortholog), consistent with the documented cytoplasmic site of NatC. Reason: Consistent with the primary cytoplasmic localization of NatC; corroborated by IDA evidence. Supporting Evidence: file:human/NAA35/NAA35-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0048659 smooth muscle cell proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity-based annotation transferred from the mouse ortholog (EGAP) linked to smooth-muscle-cell proliferation and embryonic vascular development; a peripheral developmental role. Reason: Transferred from mouse phenotype data; peripheral to NAA35's core NatC scaffold function. Supporting Evidence: file:human/NAA35/NAA35-uniprot.txt Involved in regulation of apoptosis and proliferation of smooth muscle cells |
| GO:0006474 N-terminal protein amino acid acetylation | IC PMID:19398576 Knockdown of human N alpha-terminal acetyltransferase comple... | NEW | Summary: NAA35/hMak10 is a non-catalytic auxiliary/scaffold subunit of human NatC, the complex responsible for cotranslational N-terminal acetylation. The acetyltransferase activity resides exclusively in the catalytic NAA30 subunit (GNAT fold); NAA35 contributes the scaffold and part of the NAA30-NAA35 substrate-binding interface but does not itself transfer the acetyl group. The involved_in (process) annotation is therefore appropriate, whereas a catalytic molecular-function term for NAA35 would not be. Reason: The review captures NatC complex membership but not the BP carried out by that complex. This recommends process involvement for the auxiliary subunit while explicitly not assigning catalytic acetyltransferase MF to NAA35. Supporting Evidence: PMID:19398576 the catalytic subunit hMak3 and the auxiliary subunits hMak10 and hMak31 PMID:19398576 the human NatC complex functions in cotranslational N-terminal acetylation file:human/NAA35/NAA35-deep-research-falcon.md It is crucial to emphasize that NAA35 itself does not possess catalytic acetyltransferase activity. The catalytic function resides exclusively in the NAA30 subunit, which contains the conserved GNAT (GCN5-related N-acetyltransferase) fold |
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Download this section (compressed HTML)Q: Does the NAA35/Mak10 scaffold mediate ribosome anchoring of NatC, and which surface contacts the ribosome versus the catalytic NAA30 subunit?
Q: Is the EGAP-associated smooth-muscle/vascular phenotype a direct consequence of altered NatC substrate acetylation, or an EGAP-specific moonlighting role?
Experiment: Reconstitute NatC in vitro with and without NAA35 to test whether the auxiliary subunit is required for catalytic activity and substrate selectivity of NAA30.
Experiment: Cryo-EM of the NatC-ribosome complex to map the NAA35 scaffold contacts with the ribosome and the catalytic subunit.
Experiment: N-terminomics of NAA35-depleted human cells to define the NatC-dependent N-terminal acetylome and test whether loss of the auxiliary subunit phenocopies loss of the catalytic subunit.
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