SUMF1 Human

SUMF1 is a 42 kDa protein that belongs to the sulfatase-modifying factor family . It is a soluble glycoprotein located in the endoplasmic reticulum (ER) lumen and binds calcium ions (Ca²⁺) . The primary function of SUMF1 is to oxidize the cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue, also known as C-alpha-formylglycine . This modification is essential for the catalytic activity of sulfatases, which are enzymes that hydrolyze sulfate ester bonds from a wide variety of substrates .

Sulfatases are involved in numerous biological processes, including hormone regulation, cellular signaling, and degradation of glycosaminoglycans . Deficiencies in sulfatase activity can lead to various human inherited diseases. For instance, mutations in the SUMF1 gene cause Multiple Sulfatase Deficiency (MSD), a lysosomal storage disorder characterized by the accumulation of sulfated molecules due to the lack of active sulfatases .

The mechanism by which SUMF1 modifies sulfatases has been highly conserved throughout evolution . This conservation underscores the critical role of SUMF1 in maintaining the proper function of sulfatases across different species. Studies have shown that the active site of sulfatases, which is the target of SUMF1’s modification, is the most evolutionarily constrained region, indicating its importance in the enzyme’s function .

Understanding the function and mechanism of SUMF1 has significant implications for the development of therapeutic strategies for diseases caused by sulfatase deficiencies . By targeting the SUMF1 pathway, it may be possible to develop treatments that restore the activity of defective sulfatases, thereby alleviating the symptoms of related disorders.