Succinate Dehydrogenase (Complex II) — gp2term Relation Review (`enables` → `contributes_to`)

IN_PROGRESS PIPELINEFLAGSHIP

Succinate Dehydrogenase (Complex II) — gp2term Relation Review (enables → contributes_to)

Overview

As part of the GO-CAM protein-complex annotation policy, the GO
consortium has agreed that the individual subunits of respiratory
chain complex II (succinate dehydrogenase) should all be annotated
to the molecular-function term GO:0008177 succinate dehydrogenase
(quinone) activity (and to its parent GO:0000104 succinate
dehydrogenase activity) using the contributes_to qualifier
rather than enables. No individual subunit carries out the full
succinate → quinone reaction on its own, so enables (which asserts
the gene product has the activity independently) is the wrong
gene-product-to-term relation; contributes_to (gene product
contributes to a complex-level activity) is correct.

The biology is unchanged — this is a gp2term relation
(qualifier) correction, not a term change.

Upstream tickets

The two MF terms (verified via OLS, 2026-05-19)

Term Label Definition Notes
GO:0008177 succinate dehydrogenase (quinone) activity "the overall reaction of the entire SDH complex": a quinone + succinate = a quinol + fumarate Leaf term (no children). The whole-complex activity. Always contributes_to for any single subunit.
GO:0000104 succinate dehydrogenase activity succinate + acceptor = fumarate + reduced acceptor Parent of GO:0008177 (generic acceptor; has children).

Both terms are active (not obsolete) in the GO API / OLS as of
2026-05-19. This is purely a qualifier/relation fix; no obsoletion is
involved.

Complex II subunits

Respiratory chain complex II has four subunits:

Subunit (human) Role Independent activity?
SDHA (flavoprotein, Fp) FAD-linked catalytic subunit; harbours the succinate → fumarate active site Can catalyse the succinate → fumarate half-reaction alone, but not the quinone-coupled GO:0008177 reaction
SDHB (iron-sulfur, Ip) [3Fe-4S]/[2Fe-2S]/[4Fe-4S] electron relay No
SDHC (cybL, large membrane anchor) Q-binding site, heme b No
SDHD (cybS, small membrane anchor) Q-binding site, membrane anchor No

Nuance for SDHA: the upstream blanket "contributes_to for
GO:0008177 and GO:0000104" applies cleanly to SDHB/SDHC/SDHD. For
SDHA, the complex-level GO:0008177 (quinone) is unambiguously
contributes_to, but the parent GO:0000104 (succinate +
generic acceptor → fumarate) describes the half-reaction that the Fp
subunit can catalyse via its FAD with an artificial acceptor — so
enables on GO:0000104 for SDHA specifically is defensible. Reviews
touching SDHA should flag this rather than blindly applying
contributes_to to GO:0000104. (This is exactly the kind of
relation judgement this repo is designed to surface.)

Impact on this repo

Five reviewed genes carry an existing annotation to GO:0008177.
Checked genes/**/*-ai-review.yaml for GO:0008177 / GO:0000104:

Gene File Term(s) Current handling Action needed
SDHC (human, P56378) genes/human/SDHC/SDHC-ai-review.yaml GO:0008177 IEA Structured qualifier: contributes_to present; action: ACCEPT ✅ Already aligned with #6414 — exemplar pattern
SDHA (human, P31040) genes/human/SDHA/SDHA-ai-review.yaml GO:0008177 IBA action: MODIFY → proposes GO:0000104; one qualifier: contributes_to present; prose discusses enables-vs-contributes Re-check the SDHA/GO:0000104 nuance above; confirm GO:0008177 retains contributes_to
SDHB (human, P21912) genes/human/SDHB/SDHB-ai-review.yaml GO:0008177 IEA + 2 IMP Prose says qualifier "should ideally be contributes_to"; action: ACCEPT; no structured qualifier: field on any of the three GO:0008177 rows Add structured qualifier: contributes_to to all three GO:0008177 entries
SDHD (human, O14521) genes/human/SDHD/SDHD-ai-review.yaml GO:0008177 IEA (GOA qualifier enables) Prose says qualifier "should be contributes_to"; action: ACCEPT; no structured qualifier: field Add structured qualifier: contributes_to to the GO:0008177 entry
NCGR_LOCUS67308 (9POAL plant SDH2 iron-sulfur ortholog) genes/9POAL/NCGR_LOCUS67308/NCGR_LOCUS67308-ai-review.yaml GO:0008177 IEA action: MODIFY → GO:0009055; uses core-function contributes_to_molecular_function; prose says "contributes to" Decide explicitly whether to retain MODIFY → GO:0009055 or instead keep GO:0008177 with qualifier: contributes_to

genes/human/NDUFV1 also matched the GO:0008177 grep but only in
comparative prose (NDUFV1 is a Complex I subunit) — not an
SDH annotation, so it is out of scope here.

The substantive finding: the qualifier intent is discussed in prose
in all five reviews but the structured qualifier: contributes_to
field is applied inconsistently (present on SDHC and one SDHA
entry; missing on SDHB and SDHD). The follow-up is a small,
well-defined consistency pass, not new biology.

Scope

Candidate genes for follow-up review

All five are already in the repo — this is a refresh/consistency
pass, not new reviews. Re-pull only if upstream qualifier changes
have propagated to GOA: just fetch-gene human SDHB etc.

Tier 1 — concrete consistency fixes (clear, low-judgement)

  1. SDHB (human, P21912) — add structured qualifier: contributes_to to all three GO:0008177 existing-annotation entries
    (one IEA plus two IMP rows); the prose already justifies it.
  2. SDHD (human, O14521) — same fix; GOA currently has enables,
    prose already argues for contributes_to.

Tier 2 — verify / nuance

  1. SDHA (human, P31040) — re-examine the GO:0000104-vs-GO:0008177
    split per the SDHA nuance above. Confirm GO:0008177 is
    contributes_to; decide explicitly whether GO:0000104 (FAD
    half-reaction) is enables for the Fp subunit and document the
    reasoning.
  2. NCGR_LOCUS67308 (9POAL SDH2) — decide between two curation
    strategies: keep the current MODIFY → GO:0009055 electron transfer
    activity replacement, or revise the existing-annotation review to
    retain GO:0008177 with structured qualifier: contributes_to. Do
    not simply add a qualifier if the MODIFY-to-GO:0009055 strategy
    remains the intended review outcome.

Reference exemplar (no action)

  1. SDHC (human, P56378) — already correctly uses qualifier: contributes_to with action: ACCEPT. Use as the template for
    the others.

Proposed approach

  1. Hold as a tracking project. Upstream #6414 is being worked
    group-by-group (CGD/TAIR/MGI done as of 2026-05-18); the GOA
    qualifier changes for human SDH subunits may not yet have
    propagated. Doing the consistency pass now risks re-pulling GOA
    that still shows enables.
  2. When convenient (or when GOA reflects the upstream change),
    execute the Tier 1 consistency fixes on SDHB and SDHD: add
    the structured qualifier: contributes_to to the GO:0008177
    entry, matching the existing SDHC pattern, and re-run
    just validate human SDHB / just validate human SDHD.
  3. Do the Tier 2 SDHA/9POAL checks, explicitly documenting the
    SDHA GO:0000104 half-reaction nuance.
  4. Do not create reviews for non-repo MOD orthologs — those are
    owned by the upstream groups.

Priority

Low–Medium. Small, well-bounded scope (4 genes needing a
structured-field consistency edit; 1 already correct). No new
biology and no obsoletion — the substantive value is making the
repo's gp2term qualifiers internally consistent and aligned with the
upstream Complex II policy decision. Good low-risk follow-up once the
upstream qualifier change propagates.

Status