Ring finger protein 145 (RNF145)

Ring finger protein 145 (RNF145) is an endoplasmic reticulum (ER)-resident E3 ubiquitin ligase that plays a key role in the sterol-regulated degradation of HMG-CoA reductase (HMGCR), a rate-limiting enzyme of cholesterol biosynthesis[1][3][5]. RNF145 acts by catalyzing the ubiquitination of HMGCR in conjunction with Insig proteins, leading to HMGCR degradation via the proteasome in a sterol-dependent manner[1][3]. RNF145 contains a RING finger domain required for its E3 ligase activity and a transmembrane sterol-sensing domain (SSD), sharing structural features with other proteins involved in sterol regulation, such as gp78, SCAP, and TRC8[1][3]. RNF145 is highly unstable and undergoes rapid proteasome-mediated degradation itself, with its transcription being upregulated upon cellular sterol depletion[1]. Genetic and functional studies indicate that RNF145 is partially redundant with other E3 ligases (notably gp78) in regulating cholesterol homeostasis: knockout of both RNF145 and gp78 largely abolishes sterol-induced HMGCR degradation, while loss of either alone has only partial effects[3]. RNF145 serves as an important negative regulator of cholesterol biosynthesis, and pharmacological activation of its pathway has been suggested as a potential therapeutic approach to hypercholesterolemia[3]. There is no evidence of misspelling, excessive ambiguity, or missing information for RNF145 as a target. There are currently no specific drugs reported to target RNF145 directly, nor is it presently used as a clinical biomarker or subject to known therapeutic liabilities or safety concerns.

Other names

RNF145FLJ31951

Catalyzes sterol-induced ubiquitination and degradation of HMG-CoA reductase (HMGCR); Negative regulation of endogenous cholesterol synthesis