Gsta4 review notes

Evidence summary

• [UniProtKB:P14942] UniProt describes Gsta4 as conjugating reduced glutathione to exogenous and endogenous hydrophobic electrophiles.
• PMID:11018474 The fetched GOA file uses this publication for toxic-substance binding, kept as non-core context rather than the defining activity.

Curation decisions

• Core function: glutathione S-transferase alpha-4 (glutathione transferase activity, GO:0004364).
• Specific catalytic activities and direct metabolic processes were accepted.
• Broad parent, localization, binding, and stimulus-response annotations were modified, kept non-core, or marked over-annotated according to support.

Re-review 2026-10-04

GOA changes. The refresh split the ISO glutathione transferase activity (GO:0004364, GO_REF:0000121) row by donor: one row from mouse Gsta4 (MGI:MGI:1309515, UniProt P24472) and a new seeded row from human GSTA4 (UniProtKB:O15217). No rows were retired. Total 19 rows.

Actions.
- New GO:0004364 ISO (donor human GSTA4, O15217): PENDING -> ACCEPT. Shared alpha-class catalytic activity, transferred from the one-to-one ortholog; rat tissue data show 4-HNE-specific GST A4-4 activity PMID:9774145.
- Mouse-donor GO:0004364 ISO sibling: action unchanged (ACCEPT); reason now names the donor.
- No other action changed. IEP stimulus-response rows (herbicide, zinc, nicotine, lithium) remain MARK_AS_OVER_ANNOTATED: each is an expression change [PMID:20553223 "Zn and/or PQ exposure increased gene expression of DAT, CYP2E1, GSTA4-4, MT-I and MT-II"; PMID:18082333 "chronic lithium treatment not only increased GST M1 mRNA levels, but also increased GST M3, M5 and A4 mRNA levels"]. Their supporting quotes were replaced with the GSTA4-specific sentences (previous quotes were generic background lines).
- Toxic substance binding (IPI, PMID:11018474, abstract-only) remains MARK_AS_OVER_ANNOTATED: 4-HNE is the H-site substrate, already captured by GO:0004364 PMID:11018474.
- Rows that cited only the UniProt DR GO cross-reference line (which restates the annotation itself) now also cite the FUNCTION, SUBUNIT or SUBCELLULAR LOCATION CC lines; mitochondrion now also cites PMID:9774145.
- Description rewritten to remove curation commentary.

Open questions. Whether GSTA4-4's reversible retro-Michael chemistry (see suggested_questions) merits a homeostasis-type BP term remains open.

Review follow-up 2026-10-17 (PR #4616 review). Finding 2: all twelve DR GO; cross-reference quotes replaced with the relevant UniProt CC line (CATALYTIC ACTIVITY RX+glutathione, FUNCTION conjugation line, SUBUNIT Homodimer for identical-protein-binding/homodimerization, SUBCELLULAR LOCATION Cytoplasm); the circular DR GO; entry removed from the response-to-caloric-restriction MARK row and from the mitochondrion KEEP row (which retains its PMID:9774145 and Falcon mitochondrial-import support). Validates clean; 0 stale.