gsr-1 review notes

Setup

• just fetch-gene worm gsr-1 failed three times because the UniProt gene-symbol stream search
  timed out (30 s); re-run with --uniprot-id Q93379 succeeded. UniProt entry GSHR_CAEEL Q93379
  confirmed; 25 GOA rows seeded.
• No deep-research API; manual literature survey in gsr-1-deep-research-manual.md.
• Cached extra PMIDs: 30770874 (proteostasis), 40333285 (NMD / transsulfuration suppression),
  33096249 (Hyptis extracts; peripheral, not cited).
• PMID:21199936 (molting) is abstract-only in the cache.

Key evidence

• Activity: recombinant GSR-1 reduces GSSG with NADPH, Km 34.1 uM GSSG / 12.9 uM NADPH
  PMID:23593298.
  Note that both recombinant studies expressed the GSR-1b form (Q93379-2).
• Not a thioredoxin reductase PMID:27117030.
• Dual localization by isoform PMID:27117030.
• Cytoplasmic isoform essential for embryogenesis PMID:27117030.

Decisions

• MF GO:0004362: ACCEPT on all four rows. GO:0016491 and GO:0016668 (InterPro IEA) are
  correct ancestors -> MODIFY to GO:0004362.
• FAD and NADP binding: ACCEPT (cofactor/substrate binding inherent to the family; consistent
  with human GSR review).
• Cytosol (IBA, IDA): ACCEPT. Cytoplasm (IEA from SubCell) -> MODIFY to cytosol.
• Mitochondrion (IBA, IEA, ISS): ACCEPT, organelle claim holds (2016 GFP/ TOMM-20
  co-localization of the GSR-1a MTS). Sub-compartment: added mitochondrial matrix as NEW (IC):
  lines are (1) a cleavable N-terminal MTS predicted by the authors, (2) soluble enzyme with no
  TM segment, (3) orthology to human GSR, whose mitochondrial form is in the matrix. The matrix
  location itself was not assayed in worm.
• Response to superoxide (IMP): the juglone/paraquat sensitivity is not superoxide specific
  (organic hydroperoxides also), and GR does not act on superoxide; MODIFY to cellular response
  to oxidative stress (GO:0034599), already on the gene by IBA.
• Ecdysis (IGI with trxr-1): KEEP_AS_NON_CORE; the molting role is real (GSH generated by GSR-1
  reduces cuticle disulfides) but is a tissue-specific use of the core activity; paper is
  abstract-only, so defer to curator.
• Cellular oxidant detoxification (IEA inter-ontology): KEEP_AS_NON_CORE, as in human GSR.
• No NEW BP terms: embryonic lethality, lifespan, proteostasis and mitochondrial morphology
  phenotypes are necessity evidence, not participation.