MMM1 notes (S. cerevisiae, P41800, YLL006W)

Gene-specific findings

• Historical OM assignment: PMID:11266455 -- contradicted by PMID:19556461. Hence REMOVE of the OM IDA
  row (PMID:11266455) and MARK_AS_OVER_ANNOTATED of the OM/mitochondrion proteomics HDA rows.
• Mmm1 SMP binds phospholipids: PMID:29078410; tunnel with Mdm12: PMID:29078410
• Minimal transfer unit: PMID:29279306
• Sufficiency: PMID:42095818
• Peroxisome HDA came from a TEF2-overexpression screen PMID:35563734; overproduced Mmm1 accumulates free
  in the ER PMID:30908556 -> MARK_AS_OVER_ANNOTATED.
• Beta-barrel assembly claim: PMID:17410204 -> non-core.

Deep research status (2026-10-09)

A first just deep-research-falcon yeast MMM1 --fallback perplexity-lite run completed and produced
MMM1-deep-research-falcon.md (tool-generated, not edited). A second, duplicate run timed out and its
fallback reported "Provider 'perplexity' not available"; that failure did not affect the first output.
The falcon report agrees with this review (ER-anchored SMP tether/lipid-transfer subunit; OM assignment
was a misannotation). Two points cross-checked against primary sources:

• It cites Nguyen et al. 2012 as counterevidence on PS transport; cached as PMID:22409400 and confirmed:
  PMID:22409400.
  Later in vitro (PMID:27469264, PMID:29279306) and in vivo METALIC (PMID:35654841) data, plus Vps13
  redundancy, outweigh this; phospholipid transport rows are accepted.
• It describes the 2024 Covill-Cooke bioRxiv preprint as showing mitochondria-tethered Mmm1 rescues even
  the quadruple mutant including mdm10. The published version (PMID:42095818) confirms this in the full
  text; its abstract's "provided that Mdm10 is present" refers to native ER-anchored Mmm1 acting with the
  artificial ChiMERA tether.

All other quotes were checked verbatim against publications/PMID_*.md; additional structural and
biochemical ERMES papers were found by PubMed search and cached with ai-gene-review fetch-pmid.

ERMES complex (shared context for MMM1, MDM10, MDM12, MDM34)

• ERMES is an ER-mitochondria tether: PMID:19556461
• Composition and topology: PMID:37366411; Gem1 is a fifth, regulatory subunit PMID:21945531
• Mmm1 is an ER protein, not an outer membrane protein: PMID:19556461
• SMP domains of Mmm1/Mdm12 bind phospholipids and Mdm12 bridges Mmm1 to Mdm34: PMID:26056272
• In situ architecture: PMID:37165187
• Lipid transfer by the Mmm1-Mdm12 unit in vitro: PMID:29279306; PMID:29279306
• PS transport ER-to-mitochondria needs Mmm1, Mdm12, Mdm34: PMID:27469264; PE export does not: PMID:27469264
• In vivo lipid flux: PMID:35654841
• Native ER-anchored Mmm1 can be the sole transporter (with an artificial tether) if Mdm10 is present; mitochondria-anchored Mmm1 even complements the quadruple deletion PMID:42095818: PMID:42095818
• Many ERMES phenotypes are secondary: PMID:26370498; morphology rescued by synthetic tether PMID:19556461
• Evolution (context only, computational): PMID:42822426

Complex-level curation calls applied consistently

• ERMES complex (GO:0032865), tether activity (GO:0140474), MAM contact site (GO:0044233): ACCEPT for all
  subunits that carry them.
• Phospholipid transport / aminophospholipid transport / intermembrane lipid transfer: ACCEPT. For Mdm10
  (no SMP domain) accepted on the scaffold argument (outer-membrane anchor required even for minimal
  Mmm1-only transfer), but not used as a core MF.
• Lipid transfer activity: core MF only for Mmm1 and Mdm12, as contributes_to phospholipid transfer
  activity (GO:0120014), because efficient transfer needs the Mmm1-Mdm12 complex. Mdm34 lipid binding is
  domain-inferred only; not asserted as core.
• Mitochondrion organization, mitochondrion inheritance, establishment of mitochondrion localization,
  peroxisome organization, phospholipid homeostasis: KEEP_AS_NON_CORE (real mutant phenotypes, largely
  secondary to loss of tethering/lipid supply; not participation).
• Beta-barrel/TOM assembly: ACCEPT for Mdm10 (bona fide SAM-Mdm10 subunit); KEEP_AS_NON_CORE for
  Mmm1/Mdm12 (necessity evidence, Meisinger 2007 abstract-only; possible indirect lipid effect).
• Generic protein binding (GO:0005515) IPI rows: REMOVE (interactions real, captured by complex terms).
• No NEW annotations proposed: candidate terms (e.g. phospholipid binding) are descendants of terms
  the genes already carry.