AFG3L2 PN Consistency Notes

• Generated: 2026-06-18
• Project: PROTEOSTASIS
• Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
• UniProt: Q9Y4W6
• AIGR review status: COMPLETE
• Review batch: proteostasis-batch-2026-06-03 (PR 1345)
• Batch change status: added

Source Files Checked

• AIGR review YAML: present - genes/human/AFG3L2/AFG3L2-ai-review.yaml
• AIGR review HTML: present - genes/human/AFG3L2/AFG3L2-ai-review.html
• Gene notes: present - genes/human/AFG3L2/AFG3L2-notes.md
• GOA TSV: present - genes/human/AFG3L2/AFG3L2-goa.tsv
• UniProt record: present - genes/human/AFG3L2/AFG3L2-uniprot.txt
• PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/AFG3L2.md
• PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/AFG3L2.md
• PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
• PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

• genes/human/AFG3L2/AFG3L2-deep-research-falcon.md

AIGR Review Snapshot

• Description: AFG3L2 is a mitochondrial inner membrane m-AAA protease subunit with AAA+ ATPase and zinc metalloendopeptidase domains exposed to the matrix side of the inner membrane. It assembles as AFG3L2 homohexamers and as AFG3L2-SPG7 heterohexamers that use ATP hydrolysis to unfold, translocate, and cleave mitochondrial substrates. Its major roles include protein quality control of newly synthesized or misassembled inner-membrane proteins, processing of selected mitochondrial proteins such as MRPL32 and PINK1, and regulatory degradation of substrates including EMRE/SMDT1, SLC25A39, SLC25A45, and TMBIM5/GHITM. Through these proteolytic activities AFG3L2 supports mitochondrial respiratory-chain assembly, calcium uniporter regulation, mitochondrial glutathione homeostasis, mitochondrial morphology, and neuronal maintenance.
• Existing/core annotation action counts: ACCEPT: 43; KEEP_AS_NON_CORE: 11; MARK_AS_OVER_ANNOTATED: 6; MODIFY: 17; NEW: 1

PN Consistency Summary

• Consistency: Deep research (falcon), review YAML, and PN annotation agree on the core picture: AFG3L2 is the m-AAA inner-membrane AAA+/M41 zinc metalloprotease performing mitochondrial protein QC, processing (MRPL32), and regulated degradation (EMRE, SLC25A39/45, PINK1, TMBIM5). One deliberate, well-flagged divergence: the PN group projects GO:0005759 mitochondrial matrix as the localization target, but the review rejects this (AFG3L2 is an integral inner-membrane protein with matrix-facing catalytic domains) and keeps GO:0005743 mitochondrial inner membrane. The NEW row's reason explicitly states the matrix projection is not accepted. No contradiction beyond this intentional correction.
• PN story / NEW pressure: PN class target GO:0035694 mitochondrial protein catabolic process (verified real, non-obsolete) is added as a NEW (IC) annotation and used to MODIFY the generic GO:0006508 proteolysis / GO:0030163 protein catabolic process rows. Defensible and conservative — directly supported by SLC25A39 degradation papers (PMID:37917749, 38157846). Verdict: ADD (already implemented in review).
• Evidence alignment: PN dossier carries no reference titles; review is densely evidenced (PMID:31327635, 29932645, 19748354, 27642048, 28396416, 37917749, 38157846, 41075794). PN projection TSV is cited as supporting file for GO:0035694. No PMID-level conflicts.
• Verdict: Consistent; PN GO:0035694 correctly adopted as NEW; PN matrix (GO:0005759) projection correctly overruled at gene level. Recommended edits: none required. Optional [MAP]: flag mitochondrial-proteostasis "Matrix protease" group GO:0005759 as too specific for inner-membrane matrix-facing proteases (consider GO:0005743 or no_mapping).

Full Consistency Review

• UniProt: Q9Y4W6 · batch: proteostasis-batch-2026-06-03 · review status: COMPLETE
• PN placement: Mitochondrial proteostasis|Organelle-specific protein degradation|Matrix protease ; PN-node mapping: group mapped ok_for_propagation GO:0005759 mitochondrial matrix; class mapped GO:0035694 mitochondrial protein catabolic process; branch no_mapping.
• Consistency: Deep research (falcon), review YAML, and PN annotation agree on the core picture: AFG3L2 is the m-AAA inner-membrane AAA+/M41 zinc metalloprotease performing mitochondrial protein QC, processing (MRPL32), and regulated degradation (EMRE, SLC25A39/45, PINK1, TMBIM5). One deliberate, well-flagged divergence: the PN group projects GO:0005759 mitochondrial matrix as the localization target, but the review rejects this (AFG3L2 is an integral inner-membrane protein with matrix-facing catalytic domains) and keeps GO:0005743 mitochondrial inner membrane. The NEW row's reason explicitly states the matrix projection is not accepted. No contradiction beyond this intentional correction.
• PN story / NEW pressure: PN class target GO:0035694 mitochondrial protein catabolic process (verified real, non-obsolete) is added as a NEW (IC) annotation and used to MODIFY the generic GO:0006508 proteolysis / GO:0030163 protein catabolic process rows. Defensible and conservative — directly supported by SLC25A39 degradation papers (PMID:37917749, 38157846). Verdict: ADD (already implemented in review).
• Mapping strategy: Gene refines, does not change, the node. The class→GO:0035694 mapping is correct and adopted. The group→GO:0005759 matrix mapping is too specific/wrong-compartment for AFG3L2; review's rejection is sound (matrix-facing topology ≠ matrix residence).
• Evidence alignment: PN dossier carries no reference titles; review is densely evidenced (PMID:31327635, 29932645, 19748354, 27642048, 28396416, 37917749, 38157846, 41075794). PN projection TSV is cited as supporting file for GO:0035694. No PMID-level conflicts.
• Verdict: Consistent; PN GO:0035694 correctly adopted as NEW; PN matrix (GO:0005759) projection correctly overruled at gene level. Recommended edits: none required. Optional [MAP]: flag mitochondrial-proteostasis "Matrix protease" group GO:0005759 as too specific for inner-membrane matrix-facing proteases (consider GO:0005743 or no_mapping).

PN Dossier Context

• review_batch: proteostasis-batch-2026-06-03
• review_yaml: genes/human/AFG3L2/AFG3L2-ai-review.yaml
• PN workbook rows: 1

PN row 1: Mitochondrial proteostasis | Organelle-specific protein degradation | Matrix protease

• UniProt: Q9Y4W6
• In branches: MI
• PN-node mapping records (path + ancestors):
  • [group] Mitochondrial proteostasis|Organelle-specific protein degradation|Matrix protease
    status=mapped scope=ok_for_propagation_to_go GO=[GO:0005759 mitochondrial matrix]
    rationale: This PN group identifies matrix-local protease systems. The source is a compartmental proteostasis bucket, so the mitochondrial matrix cellular-component term is the conservative propagation target.
  • [class] Mitochondrial proteostasis|Organelle-specific protein degradation
    status=mapped scope=ok_for_propagation_to_go GO=[GO:0035694 mitochondrial protein catabolic process]
    rationale: This PN class groups mitochondrial protein-degradation pathways. GO mitochondrial protein catabolic process is the conservative shared target.
  • [branch] Mitochondrial proteostasis
    status=no_mapping scope= GO=[]
    rationale: Reviewed as a top-level PN branch. This is a systems/taxonomy umbrella, not a direct GO assertion; narrower child curations carry any propagating GO mappings.

Projected GO annotations (2)

• GO:0035694 mitochondrial protein catabolic process | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Mitochondrial proteostasis|Organelle-specific protein degradation
• GO:0005759 mitochondrial matrix | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Mitochondrial proteostasis|Organelle-specific protein degradation|Matrix protease

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.