Mitochondrion Targeting Sequence Binding — Obsoletion & Replacement

IN_PROGRESS OBSOLETIONFLAGSHIP

Warnings (1)

Mitochondrion Targeting Sequence Binding — Obsoletion & Replacement

Overview

A GO obsoletion proposal will obsolete the molecular-function term
GO:0030943 mitochondrion targeting sequence binding (defined as "Binding to a
mitochondrion targeting sequence, a specific peptide sequence that acts as a
signal to localize the protein within the mitochondrion"). The upstream
rationale is that the curated content is better captured by a non-binding
receptor activity term rather than a generic "binding" term: the ontology
ticket proposes a New Term Request (NTR) for
mitochondrial signal sequence receptor activity as the replacement,
mirroring the existing nuclear/vacuolar pattern
(GO:0061608 nuclear import signal receptor activity,
GO:0005049 nuclear export signal receptor activity,
GO:0010209 vacuolar sorting signal receptor activity).

Crucially, the go-annotation curators note that a simple replaced_by
cannot be applied, because the existing annotations are not only to the
receptor — they span TOM cytosolic receptors, inner-membrane TIM
channel/receptor components, the TIM23 holo-complex, and at least one
non-canonical plant protein. Each annotation therefore needs individual review
to decide whether the new receptor MF is appropriate or whether a different
term (or removal) is the right outcome.

This is part of the broader mitochondrial-import GO-CAM reorganization
(go-ontology#31711) and is a sibling of the "signal sequence binding and
children" review (go-ontology#31419, which also drives the
GO:0008139 nuclear localization sequence binding obsoletion in
go-annotation#6435). It complements — but does not overlap with — the
BP-focused [[MITOCHONDRIAL_IMPORT_PATHWAYS]] project, which covers the import
pathway terms rather than this MF term.

Upstream tickets

Obsoletion plan (per upstream)

Obsoleted term ID Proposed replacement
mitochondrion targeting sequence binding (MF) GO:0030943 NTR mitochondrial signal sequence receptor activity (a receptor, non-binding MF) — applied per-annotation, not as a blanket replaced_by

Term labels verified in OLS on 2026-05-28:

Affected experimental / curated annotations (18)

Retrieved from the QuickGO annotation API on 2026-05-28
(goId=GO:0030943, manual / experimental + ComplexPortal NAS). Matches the
upstream group tally (ComplexPortal 4, FlyBase 2, HGNC-UCL 1, RGD 2, SGD 7,
TAIR 2 = 18).

# Source Accession Symbol Organism Evidence Reference
1 RGD UniProtKB:A4F267 Tomm40l Rat IDA PMID:17437969
2 RGD UniProtKB:Q62760 Tomm20 Rat IDA PMID:16511083
3 SGD UniProtKB:P07213 TOM70 S. cerevisiae IMP PMID:11054285
4 SGD UniProtKB:P32897 TIM23 S. cerevisiae IDA PMID:8858146
5 SGD UniProtKB:P32897 TIM23 S. cerevisiae IMP PMID:8858146
6 SGD UniProtKB:P35180 TOM20 S. cerevisiae IDA PMID:9252394
7 SGD UniProtKB:Q02776 TIM50 S. cerevisiae IDA PMID:18418384
8 SGD UniProtKB:Q02776 TIM50 S. cerevisiae IDA PMID:19144822
9 SGD UniProtKB:Q12328 TIM22 S. cerevisiae IDA PMID:11864609
10 HGNC-UCL UniProtKB:Q15388 TOMM20 Human IDA PMID:14557246
11 FlyBase UniProtKB:Q15388 TOMM20 Human IDA PMID:35733257
12 FlyBase UniProtKB:Q9NS69 TOMM22 Human IDA PMID:35733257
13 TAIR UniProtKB:Q9LMG7 PAP2 A. thaliana IPI PMID:26304849
14 TAIR UniProtKB:Q9LMG7 PAP2 A. thaliana IPI PMID:26304849
15 ComplexPortal ComplexPortal:CPX-539 TIM23 complex (yeast) S. cerevisiae NAS PMID:16107694
16 ComplexPortal ComplexPortal:CPX-6127 TIM23 complex (yeast) S. cerevisiae NAS PMID:16107694
17 ComplexPortal ComplexPortal:CPX-6129 TIM23 complex (human) Human NAS PMID:10339406
18 ComplexPortal ComplexPortal:CPX-6130 TIM23 complex (human) Human NAS PMID:10339406

Note: rows 11–12 carry assignedBy=FlyBase on human accessions — confirmed
directly from QuickGO, presumably a cross-organism assertion; flagged here for
the curator's awareness.

On top of these 18 curated records, GO:0030943 currently has ~12,091 total
annotations (QuickGO, 2026-05-28), overwhelmingly IEA (TreeGrafter,
GO_REF:0000118) and IBA (GO_REF:0000033). These will be retired/redirected
automatically once the term is obsoleted, but the volume illustrates how far a
small set of curated TOM-receptor annotations has propagated.

Why a blanket replaced_by does not work

The annotations fall into biologically distinct classes, only some of which are
true presequence receptors:

Impact on this repo

Several affected gene products — or their human orthologs — already have
*-ai-review.yaml files that annotate GO:0030943 (verified 2026-05-28):

Gene Path Relation to affected set Current handling of GO:0030943
TOMM20 (human, Q15388) genes/human/TOMM20 Directly affected (rows 10–11) ACCEPT (core MF — presequence receptor)
TOMM22 (human, Q9NS69) genes/human/TOMM22 Directly affected (row 12) present (IDA + IBA)
TIM22 (yeast, Q12328) genes/yeast/TIM22 Directly affected (row 9) retained as "best available", with a caveat that the term is broader than the internal-signal binding it actually does
TOMM70 (human) genes/human/TOMM70 Ortholog of affected yeast TOM70 present (IBA)
TOMM40 (human) genes/human/TOMM40 TOM channel; carries term via IBA present (IBA)
TIMM50 (human) genes/human/TIMM50 Ortholog of affected yeast TIM50 present
TIMM22 (human) genes/human/TIMM22 Ortholog of affected yeast TIM22 present
ACL4 (yeast) genes/yeast/ACL4 Not in curated set; IBA over-propagation already REMOVE (Acl4 is an Rpl4 chaperone; no MTS binding) — a worked example of the IBA fallout

When the obsoletion + NTR land, these reviews will need a MODIFY pass:
remap the TOM-receptor annotations to the new
mitochondrial signal sequence receptor activity MF, and handle TIM22 and any
complex/plant cases per the considerations above.

Scope

Candidate genes for initial review

Listed in priority order. The first three are the clean, high-value receptor
cases that already have reviews in this repo and would directly exercise the
new MF once minted.

  1. TOMM20 (human, Q15388) — canonical N-terminal presequence receptor;
    directly affected by two of the 18 annotations; review already
    ACCEPTs GO:0030943 as the core MF. Best positive control for the new
    mitochondrial signal sequence receptor activity.
  2. TOMM22 (human, Q9NS69) — TOM central/co-receptor; directly affected.
  3. TOMM70 (human) — receptor for carrier/hydrophobic precursors; ortholog
    of the affected yeast TOM70 (P07213, IMP).
  4. TIM50 / TIMM50 — trans-side presequence handoff receptor; affected yeast
    TIM50 (Q02776) plus the human ortholog review here.
  5. TIM22 (yeast, Q12328) — special case: carrier pathway uses internal
    signals; decide whether the new receptor MF applies or whether the
    annotation should be removed/replaced with a carrier-import term.
  6. PAP2 (Arabidopsis, Q9LMG7) — non-canonical IPI annotation; case-by-case.
  7. TIM23 complex (ComplexPortal CPX-539/6127/6129/6130) — complex-level
    handling once the NTR exists.

Proposed approach

  1. Wait for the NTR + obsoletion to land. The replacement MF
    (mitochondrial signal sequence receptor activity) is not yet minted in GO
    (OLS, 2026-05-28). go-ontology#32142 is closed but the new GO ID must be
    confirmed before any remapping.
  2. Pre-stage MODIFY proposals on the existing repo reviews (TOMM20, TOMM22,
    TOMM70, TIMM50, TIMM22, TOMM40), changing GO:0030943 → the new receptor MF
    for the genuine cytosolic/trans-side receptors.
  3. Triage the non-receptor cases explicitly: TIM22 (internal-signal carrier
    channel), PAP2 (plant IPI), and the TIM23 holo-complex records. These are
    the reason upstream avoided a blanket replaced_by.
  4. Note the IBA/IEA fallout (~12k annotations): once GO:0030943 is
    obsoleted, the GO_Central IBA and TreeGrafter IEA pipelines will need to be
    reseeded against the new MF. The yeast ACL4 review (already REMOVE) is a
    concrete example of an IBA that should not be carried over to the new
    receptor term.
  5. Coordinate with [[MITOCHONDRIAL_IMPORT_PATHWAYS]] so MF remapping and the
    BP pathway model stay consistent for shared TOM/TIM genes.

Priority

Medium. Only 18 curated annotations, and several of the key genes already have
reviews here, so the marginal curation effort is low. The receptor biology is
uncontroversial, so the main blocker is external (the NTR GO ID is not yet
minted). The large IEA/IBA tail makes this more impactful than the very small
obsoletions, but no curator group is blocked waiting on AI Gene Review.

Status