CGRRF1 is one of 37 human RING-finger + transmembrane proteins computationally selected as candidate ERAD E3 ligases; it localizes to the ER (colocalization with PDI) and its expression is up-regulated by ER stress and by ATF6.

In an in vitro autoubiquitination assay with the E2 UbcH5c/UBE2D3, CGRRF1 did NOT exhibit E3 activity, and it conferred no resistance to ER stress, unlike RNFT1 and RNF185.

CGRRF1 protein interactions in GOA derive from the HuRI high-throughput binary (Y2H) interactome map; interactors are mostly other membrane/ER-Golgi proteins and are not individually validated.

CGRRF1 is treated as one of ~25 ER-resident transmembrane RING E3 ligases; its transcript is induced by acute ER stress, and Evi/WLS/GPR177 is stated to have been established as a novel target for regulated ERAD by CGRRF1 (Glaeser et al., 2018), independently corroborating the E3-ligase/ERAD/Evi-substrate role.

LLM-synthesized deep research report. Its CGRRF1-specific core finding - that CGRRF1 is a functional ER E3 ligase that, with the cognate E2 UBE2J2, ubiquitinates the Wnt cargo receptor Evi/WLS for regulated ERAD (siRNA depletion raises Evi, TUBE2 pulldown shows reduced Evi ubiquitination, co-IP, RING-mutant stabilisation) - traces to Glaeser et al. 2018 (EMBO J) and is independently corroborated by the cached Fenech et al. 2020 (PMID:32614325).

Family/inference-level statements in the report (general ERAD machinery roles drawn from Christianson 2023 and Wang 2025 reviews, the candidate inner-nuclear-membrane localization near emerin/LBR from Cheng et al. 2022 proximity labeling, K11/K48/K63 chain linkages, and the cancer/TCGA Wnt-secretion speculation) are broader inferences and should not be asserted as CGRRF1-specific molecular function without primary verification.

CGRRF1 was originally isolated as CGR19, a p53-induced cell growth regulatory gene encoding a RING-finger protein whose overexpression inhibits growth of several cell lines.