MDM12 notes (S. cerevisiae, Q92328, YOL009C)

Gene-specific findings

• Soluble/peripheral subunit whose localization depends on partners: PMID:19556461
• Original OM assignment: PMID:9024686 (described as integral; later peripheral).
• Phospholipid-binding channel: PMID:27821511
• Free Mdm12 transfer is weak: PMID:29279306
• Inheritance phenotype: PMID:9024686 -> mitochondrion inheritance kept non-core.
• Nucleus and plasma membrane HDA rows from the replication-stress GFP screen PMID:22842922 have no
  targeted support -> MARK_AS_OVER_ANNOTATED; cytoplasm kept non-core.
• Peroxisome number phenotype depends on Mmm1/Mdm12 stoichiometry PMID:30908556.

Deep research status (2026-10-09)

A first just deep-research-falcon yeast MDM12 --fallback perplexity-lite run completed and produced
MDM12-deep-research-falcon.md (tool-generated, not edited). A second, duplicate run timed out and its
fallback reported "Provider 'perplexity' not available"; that did not affect the first output. The falcon
report is consistent with this review. Its statements were cross-checked against primary sources:
it describes the 2024 Covill-Cooke bioRxiv preprint (mitochondria-anchored Mmm1 rescues even the quadruple
ERMES deletion); the published version (PMID:42095818) confirms this in its full text, and the abstract's
"provided that Mdm10 is present" refers to native ER-anchored Mmm1 acting with the ChiMERA tether. It also
cites Nguyen et al. 2012 (PMID:22409400, now cached), whose claim that ERMES has no direct role in PS
transport is outweighed by later in vitro and in vivo METALIC data, and whose finding that inheritance
defects are secondary to morphology supports the non-core calls. All quotes used were checked verbatim
against publications/PMID_*.md.

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.