Sulphatase activities are regulated by the interaction of sulphatase-modifying factor 1 with SUMF2.
Sulphatases undergo a unique post-translational modification that converts a highly conserved cysteine located within their active site into formylglycine. This modification is necessary for the catalytic activities of the sulphatases, and it is generated by the protein product of sulphatase-modifying factor 1 (SUMF1), the gene mutated in multiple sulphatase deficiency (MSD). A paralogous gene, SUMF2, was discovered through its sequence similarity to SUMF1. We present evidence that SUMF2 colocalizes with SUMF1 within the endoplasmic reticulum and that the two proteins form heterodimers. SUMF1 and SUMF2 also form homodimers. In addition, SUMF2 is able to associate with the sulphatases with and without SUMF1. We have previously shown that co-transfection of SUMF1 with the sulphatase complementary DNAs greatly enhances the activities of the overexpressed sulphatases. Here, we show that SUMF2 inhibits the enhancing effects of SUMF1 on sulphatases, suggesting that the SUMF1-SUMF2 interaction represents a further level of control of these sulphatase activities.
Zito
Ester
E
Telethon Institute of Genetics and Medicine (TIGEM), via P. Castellino, 111, Naples, Italy.
Fraldi
Alessandro
A
Pepe
Stefano
S
Annunziata
Ida
I
Kobinger
Gary
G
Di Natale
Paola
P
Ballabio
Andrea
A
Cosma
Maria Pia
MP
D000818:Animals; D019281:Dimerization; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D006801:Humans; D007066:Iduronate Sulfatase / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051379:Mice; D050862:Oxidoreductases Acting on Sulfur Group Donors; D025941:Protein Interaction Mapping; D013429:Sulfatases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D050862:Oxidoreductases Acting on Sulfur Group Donors; C480483:SUMF1 protein, human; C500803:SUMF2 protein, human; D013429:Sulfatases; D007066:Iduronate Sulfatase