NIH R01 · 2024
UbiA prenyltransferase domain-containing protein-1 (UBIAD1) uses the nonsterol isoprenoid geranylgeranyl pyrophosphate (GGpp) to synthesize a form of vitamin K called menaquinone-4 (MK-4). UBIAD1 is multifunctional as indicated by the association of mutations in human UBIAD1 with Schnyder corneal dystrophy (SCD). This rare autosomal dominant eye disease is characterized by progressive corneal opacification owing to abnormal accumulation of cholesterol. Our studies revealed that sterols cause UBIAD1 to bind endoplasmic reticulum (ER)-localized HMG CoA reductase (HMGCR), the rate-limiting enzyme in synthesis of cholesterol and essential nonsterol isoprenoids including farnesyl pyrophosphate,…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.