## CGRRF1
- **UniProt:** Q99675 (CGR19, RNF197) · **batch:** proteostasis-batch-2026-06-07 · **review status:** COMPLETE
- **PN placement:** `UPS|E3 ubiquitin and UBL ligases|RING|other|other` ; **PN-node mapping:** RING/other subtype+type no_mapping; RING group mapped → GO:0061630 ubiquitin protein ligase activity (ok_for_propagation, new_to_goa); class context_only (GO:0061630, too_broad).
- **Consistency:** Partial conflict / caveat. Deep-research, review, and PN agree CGRRF1 is an ER-membrane RING + transmembrane protein with the structural hallmarks of an ERAD E3 ligase (RING ZN_FING 274-309, PDB 2EA5; ER localization; ATF6/UPR-induced). BUT the review (and notes) emphasize a NEGATIVE result: the only published in vitro autoubiquitination assay (E2 UbcH5c/UBE2D3) showed NO E3 activity, and no substrate is known (PMID:27485036). The review therefore deliberately does NOT accept ubiquitin ligase activity as a curated function — it has no GO:0061630 in existing_annotations and frames E3 activity only structurally in core_functions + suggested_experiments. PN's RING-group projection of GO:0061630 thus conflicts with the review's explicit caution.
- **PN story / NEW pressure:** Over-reaches given negative biochemical evidence. PN projects GO:0061630 (real term) as new_to_goa from RING-group membership, but the catalytic activity is unproven (negative in vitro test, no substrate). This is a homology/architecture inference the review intentionally withheld. Recommend NOT propagating GO:0061630 as an asserted MF; at most an ISS/structural inference clearly flagged as unverified-by-assay. The review's well-supported content is ER localization (GO:0005783, IDA) and ER-stress/UPR induction.
- **Mapping strategy:** This gene argues for caution on the RING-group → GO:0061630 projection. Domain-based RING-group propagation is reasonable for ligases with positive evidence, but CGRRF1 is a counterexample (RING present, activity not demonstrated, one assay negative). Flag CGRRF1 as a RING-group member that should NOT auto-inherit GO:0061630 without experimental support; the type node is already no_mapping which is appropriate.
- **Evidence alignment:** PN cites 19489725 (the ERAD-RING-ligase genome-wide screen = PMID:27485036, the review's central source) — good direct overlap. Review additionally uses PMID:8968090 (p53/CGR19 growth) and PMID:32296183 (HuRI). PN and review share the key ERAD-screen reference.
- **Verdict:** Caveated inconsistency — PN's GO:0061630 over-reaches relative to the review's deliberate non-acceptance (negative in vitro E3 assay). Defer to review's caution.
- **Recommended edits:** Suppress/flag the RING-group GO:0061630 projection for CGRRF1 (unproven catalytic activity; one in vitro assay negative); if retained, mark as homology-only/unverified rather than ok_for_propagation. [MAP]