POFUT1

This gene encodes a member of the glycosyltransferase O-Fuc family. This enzyme adds O-fucose through an O-glycosidic linkage to conserved serine or threonine residues in the epidermal growth factor-like repeats of a number of cell surface and secreted proteins. O-fucose glycans are involved in ligand-induced receptor signaling. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq]

Full Name

protein O-fucosyltransferase 1

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).

Biological Process

AngiogenesisIEA:Ensembl
Fucose metabolic processIEA:UniProtKB-KW
Heart developmentIEA:Ensembl
Nervous system developmentIEA:Ensembl
Notch signaling pathway1 PublicationNAS:UniProtKB
O-glycan processingManual Assertion Based On ExperimentTAS:UniProtKB
Protein O-linked fucosylationManual Assertion Based On ExperimentIDA:UniProtKB
Protein O-linked glycosylationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of Notch signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of transcription, DNA-templated1 PublicationNAS:UniProtKB
SomitogenesisIEA:Ensembl

Cellular Location

Endoplasmic reticulum

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.

PTM

N-glycosylated.