Formylglycine-generating sulphatase enzyme domain (IPR005532)

Short name: FGE_dom

Domain relationships

  • C-type lectin fold (IPR016187)
    • Formylglycine-generating sulphatase enzyme domain (IPR005532)


This domain is found in eukaryotic proteins [PMID: 14563551] required for post-translational sulfatase modification (SUMF1). These proteins are associated with the rare disorder multiple sulfatase deficiency (MSD) [PMID: 15146462]. The protein product of the SUMF1 gene is FGE, formylglycine (FGly)-generating enzyme, which is a sulfatase. Sulfatases are enzymes essential for degradation and remodelling of sulfate esters, and formylglycine (FGly), the key catalytic in the active site, is unique to sulfatases [PMID: 15907468]. FGE is localised to the endoplasmic reticulum (ER) and interacts with and modifies the unfolded form of newly synthesised sulfatases. FGE is a single-domain monomer with a surprising paucity of secondary structure that adopts a unique fold which is stabilised by two Ca2+ ions. The effect of all mutations found in MSD patients is explained by the FGE structure, providing a molecular basis for MSD. A redox-active disulfide bond is present in the active site of FGE. An oxidised cysteine residue, possibly cysteine sulfenic acid, has been detected that may allow formulation of a structure-based mechanism for FGly formation from cysteine residues in all sulfatases [PMID: 18157819]. In Mycobacteria and Treponema denticola this enzyme functions as an iron(II)-dependent oxidoreductase [PMID: 20420449, PMID: 15064399].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.