POFUT1
Function
Catalyzes the reaction that attaches fucose through an O-glycosidic linkage to a conserved serine or threonine residue found in the consensus sequence C2-X(4,5)-[S/T]-C3 of EGF domains, where C2 and C3 are the second and third conserved cysteines. Specifically uses GDP-fucose as donor substrate and proper disulfide pairing of the substrate EGF domains is required for fucose transfer. Plays a crucial role in NOTCH signaling. Initial fucosylation of NOTCH by POFUT1 generates a substrate for FRINGE/RFNG, an acetylglucosaminyltransferase that can then extend the fucosylation on the NOTCH EGF repeats. This extended fucosylation is required for optimal ligand binding and canonical NOTCH signaling induced by DLL1 or JAGGED1. Fucosylates AGRN and determines its ability to cluster acetylcholine receptors (AChRs).
Involvement in disease
Dowling-Degos disease 2
DDD2
An autosomal dominant genodermatosis. Affected individuals develop a postpubertal reticulate hyperpigmentation that is progressive and disfiguring, and small hyperkeratotic dark brown papules that affect mainly the flexures and great skin folds. Patients usually show no abnormalities of the hair or nails.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Protein modification; protein glycosylation.
Post-translational modifications
N-glycosylated.
Sequence Similarities
Belongs to the glycosyltransferase 65 family.
Tissue Specificity
Highly expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
Cellular localization
- Endoplasmic reticulum
Alternative names
FUT12, KIAA0180, POFUT1, GDP-fucose protein O-fucosyltransferase 1, Peptide-O-fucosyltransferase 1, O-FucT-1