NAA35 PN Consistency Notes
- Generated: 2026-06-18
- Project: PROTEOSTASIS
- Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
- UniProt: Q5VZE5
- AIGR review status: COMPLETE
- Review batch: proteostasis-batch-2026-06-07c
- Batch change status: added
Source Files Checked
Deep Research Files
- No
*-deep-research*.md file found in this gene directory.
AIGR Review Snapshot
- Description: 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.
- Existing/core annotation action counts: ACCEPT: 10; KEEP_AS_NON_CORE: 8; NEW: 1
PN Consistency Summary
- Consistency: Strong. All three sources agree NAA35 (MAK10/EGAP) is the large non-catalytic auxiliary/scaffold subunit of NatC; no catalytic MF is asserted (correct). PN-node mapping (NatC complex CC; Nt-acetylation BP) is consistent with the auxiliary role.
- PN story / NEW pressure: PN projects BP GO:0006474 (verified real; confirmed absent from NAA35 GOA). For a non-catalytic scaffold an
involved_in BP of N-terminal acetylation is defensible (it is part of the complex that performs the process), and complements the review's CC-only core. Conclusion: ADD GO:0006474 (involved_in) is reasonable; the catalytic MF must NOT be added (NAA35 is non-catalytic). Not an over-reach.
- Evidence alignment: Concordant. Review/notes use PMID:19398576 (NatC; hMak10 auxiliary; IDA GO:0031417, IMP GO:0043066), PMID:37891180, plus mouse EGAP origin (PMID:16484612, cited in notes) for the smooth-muscle/vascular ISS/IEA. PN row carries no titles. No divergence.
- Verdict: Consistent, high-quality. Internal note vs YAML mismatch: notes say PMID:32296183 (TRIM7) protein-binding should be MARK_AS_OVER_ANNOTATED, but YAML uses KEEP_AS_NON_CORE (minor, defensible either way). Recommended edits: Add BP GO:0006474 (involved_in, auxiliary subunit of the acetylating complex) to NAA35 review [YAML]; optionally reconcile PMID:32296183 action with notes (KEEP_AS_NON_CORE vs MARK_AS_OVER_ANNOTATED) [YAML].
Full Consistency Review
- UniProt: Q5VZE5 · batch: proteostasis-batch-2026-06-07c · review status: COMPLETE
- PN placement:
Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide|NatC complex component ; PN-node mapping: subtype mapped→GO:0031417 NatC complex (ok_for_propagation); type mapped→GO:0006474 N-terminal protein amino acid acetylation (ok_for_propagation, new_to_goa)
- Consistency: Strong. All three sources agree NAA35 (MAK10/EGAP) is the large non-catalytic auxiliary/scaffold subunit of NatC; no catalytic MF is asserted (correct). PN-node mapping (NatC complex CC; Nt-acetylation BP) is consistent with the auxiliary role.
- PN story / NEW pressure: PN projects BP GO:0006474 (verified real; confirmed absent from NAA35 GOA). For a non-catalytic scaffold an
involved_in BP of N-terminal acetylation is defensible (it is part of the complex that performs the process), and complements the review's CC-only core. Conclusion: ADD GO:0006474 (involved_in) is reasonable; the catalytic MF must NOT be added (NAA35 is non-catalytic). Not an over-reach.
- Mapping strategy: Correct. Subtype→NatC complex exact CC is the safe target for an auxiliary subunit; BP propagated at type level. No node-mapping change warranted.
- Evidence alignment: Concordant. Review/notes use PMID:19398576 (NatC; hMak10 auxiliary; IDA GO:0031417, IMP GO:0043066), PMID:37891180, plus mouse EGAP origin (PMID:16484612, cited in notes) for the smooth-muscle/vascular ISS/IEA. PN row carries no titles. No divergence.
- Verdict: Consistent, high-quality. Internal note vs YAML mismatch: notes say PMID:32296183 (TRIM7) protein-binding should be MARK_AS_OVER_ANNOTATED, but YAML uses KEEP_AS_NON_CORE (minor, defensible either way). Recommended edits: Add BP GO:0006474 (involved_in, auxiliary subunit of the acetylating complex) to NAA35 review [YAML]; optionally reconcile PMID:32296183 action with notes (KEEP_AS_NON_CORE vs MARK_AS_OVER_ANNOTATED) [YAML].
- 2026-06-18 follow-up: Implemented the high-confidence YAML edit: added GO:0006474 N-terminal protein amino acid acetylation as a NEW BP recommendation and core process for the NatC auxiliary subunit, using IC to reflect inference from NatC complex membership rather than direct catalytic activity. The optional protein-binding action-style reconciliation remains separate.
PN Dossier Context
- review_batch: proteostasis-batch-2026-06-07c
- review_yaml: genes/human/NAA35/NAA35-ai-review.yaml
- PN workbook rows: 1
PN row 1: Translation | Cytosolic translation | Nascent peptide husbandry | N-terminal acetylation of nascent peptide | NatC complex component
- UniProt: Q5VZE5
- In branches: TR
- PN-node mapping records (path + ancestors):
- [subtype] Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide|NatC complex component
status=mapped scope=ok_for_propagation_to_go GO=[GO:0031417 NatC complex]
rationale: Exact cellular-component match: members are subunits of the NatC N-terminal acetyltransferase complex. Complements the parent BP mapping with the complex-membership CC term.
- [type] Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide
status=mapped scope=ok_for_propagation_to_go GO=[GO:0006474 N-terminal protein amino acid acetylation]
rationale: This PN type denotes N-terminal acetyltransferase machinery acting on nascent peptides. The GO N-terminal acetylation process is the direct target.
- [group] Translation|Cytosolic translation|Nascent peptide husbandry
status=no_mapping scope= GO=[]
rationale: Reviewed as a broad PN category rather than a single GO class. The member genes span multiple activities, complexes, or contexts, so direct propagation from this node would overstate the shared biology.
- [class] Translation|Cytosolic translation
status=context_only scope=too_broad_to_propagate GO=[GO:0002181 cytoplasmic translation]
rationale: The PN class Cytosolic translation is centered on the cytoplasmic translation apparatus and process, but it also houses supporting machinery such as ribosome biogenesis factors. The GO process term is a useful high-level label for the class, but propagating it to all members would over-annotate genes whose PN placement is through assembly or maturation context rather than core cytoplasmic translation.
- [branch] Translation
status=context_only scope=too_broad_to_propagate GO=[GO:0006412 translation]
rationale: The PN Translation branch is organized around the translation apparatus and immediately associated cotranslational quality-control systems. GO translation is the closest high-level process label, but the PN branch also contains adjacent machinery such as ribosome biogenesis and nascent-chain handling. Keeping this relationship is useful for interpretation, but it is too broad to project safely onto every member.
Projected GO annotations (1)
- GO:0006474 N-terminal protein amino acid acetylation | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide
Note
This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.