Allosteric regulation of UBIAD1 trafficking from ER to Golgi revealed by chemical genetic screening.

ABSTRACT: Schnyder corneal dystrophy (SCD) is a rare autosomal dominant condition characterized by the opacification of the cornea owing to the abnormal deposition of cholesterol. SCD-associated mutations have been identified in the gene encoding UbiA prenyltransferase domain-containing protein-1 (UBIAD1), which uses geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K₂ subtype menaquinone-4 (MK-4). Beyond its enzymatic role, UBIAD1 serves as a key regulator of the endoplasmic reticulum (ER)-localized enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the rate-limiting enzyme in the mevalonate pathway that produces cholesterol and nonsterol isoprenoids such as GGpp and MK-4. Sterol-induced binding to UBIAD1 inhibits the sterol-accelerated ER-associated degradation

SUBMITTER: Jun DJ 

PROVIDER: S-EPMC12107145 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature