Mitochondrion–ER membrane tethering: obsoletion

GO:1990456 (BP) → GO:0140474 mitochondrion-ER membrane tether activity (MF)

AI Gene Review · projects/MITO_ER_TETHERING_OBSOLETION · 2026

Bottom line

  • GO obsoleted GO:1990456 because tethering is a molecular function; curators should consider GO:0140474 instead.
  • 30 upstream annotations (16 still pending) and 3 mappings move; 5 reviews here carry the old term (human VMP1, CALM1; mouse Calm1/2/3).
  • Scoped, not yet started: none of those rows has been refreshed, and no canonical tether (PDZD8, MFN2, VAPB, ERMES) is reviewed here.

Old term → replacement

What a tether is

Why it moved to MF

  • A tether physically bridges the ER and outer mitochondrial membranes: a binding activity of one gene product or complex.
  • The parallel ER–PM and peroxisome–chloroplast tether terms went the same way.
  • GO:0140474's definition: brings the two membranes together "via membrane lipid binding or by interacting with a mitochondrial outer membrane protein".
  • So a review should ask of each row: does the gene product itself bridge the membranes?

The five affected reviews

Review Row(s) Current action Note
human VMP1 IDA PMID:28890335 ACCEPT modulates ER–mito contacts
human CALM1 IDA PMID:28890335 ACCEPT review text is Reactome/TAS boilerplate
mouse Calm1 IEA, ISO, ISS KEEP_AS_NON_CORE propagated
mouse Calm2, Calm3 IEA KEEP_AS_NON_CORE propagated

The project proposes REMOVE for the calmodulin rows at refresh: nothing shows calmodulin itself bridges the membranes. VMP1 needs a check against the GO:0140474 definition.

Status and next steps

  • 2026-05-09: project created. Upstream, SGD, UniProt and FlyBase are marked done.
  • 2026-09-26: OLS lists GO:1990456 obsolete; the 5 reviews still show pre-obsoletion actions.
  • Next: refresh VMP1, CALM1, Calm1/2/3; then review PDZD8 (the IPR039275 target) and MFN2, and yeast MMM1 + MDM12.

Upstream: go-annotation#6397 · go-ontology#31875
Read more: projects/MITO_ER_TETHERING_OBSOLETION.md