Protein O-fucosyltransferase 1 (POFUT1)

Protein O-fucosyltransferase 1 (POFUT1) is an enzyme localized in the endoplasmic reticulum responsible for catalyzing the transfer of fucose residues from GDP-fucose to serine or threonine residues on EGF-like repeats in specific substrate proteins, most notably Notch receptors. This O-fucosylation is essential for efficient Notch signaling—a pathway fundamental for cell differentiation, proliferation, and apoptosis throughout embryonic development and adult tissue maintenance. Mutations in POFUT1 cause autosomal dominant pigmentary disorders such as Dowling-Degos disease and may contribute to oncogenesis in contexts of aberrant Notch activity, such as T-cell acute lymphoblastic leukemia. POFUT1 is the only enzyme known to catalyze this specific glycosylation modification, and it also has important chaperoning functions for proper folding and trafficking of Notch and other EGF-like domain proteins. There are currently no approved drugs that directly target POFUT1, but it is considered a therapeutic target due to its role in disease.

Other names

FUT12KIAA0180O-FucT-1O-FUTO-Fuc-TOFUCT1GDP-fucose protein O-fucosyltransferase 1peptide-O-fucosyltransferase 1o-fucosyltransferase protein

Inhibition of POFUT1 would block O-fucosylation of Notch and related proteins, disrupting Notch signaling; potential antitumor effect in Notch-driven cancers. No drugs with approved mechanism yet