The formylglycine (FGly) modification of an active-site cysteine, generated by SUMF1 within the ER, is required for the catalytic activity of the sulphatases (including GALNS); SUMF2 modulates SUMF1 activity.

Galactose-6-sulfatase (GALNS) hydrolyses sulfate groups of chondroitin sulfate; modulating GALNS expression (overexpression vs siRNA silencing) inversely changes cellular chondroitin sulfate content, demonstrating a role in chondroitin sulfate catabolism.

Crystal structure of human GALNS (EC 3.1.6.4); the enzyme removes 6-sulfate groups from terminal N-acetylgalactosamine-6-sulfate (chondroitin-6-sulfate) and galactose-6-sulfate (keratan sulfate). Formylglycine-generating enzyme converts Cys79 to a formylglycine nucleophile; the enzyme is a Ca2+-binding homodimer.

Shotgun proteomics of exosomes from expressed prostatic secretions in urine detected ~900 proteins, among them GALNS, consistent with its presence in the secreted/extracellular-exosome fraction.

Immunostaining of cultured lung fibroblasts shows GALNS in a lysosomal localisation in both ever smokers and COPD patients, confirming lysosomal localisation.

Chromosome-mapping study assigning the human N-acetylgalactosamine-6-sulfate sulfatase (GALNS; EC 3.1.6.4) gene to chromosome 16q24; the paper does not assay a 4-sulfatase activity.

Original demonstration of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) activity in man and its absence in Morquio disease; source of the EC 3.1.6.4 catalytic-activity assignment in UniProt.

FUNCTION: lysosomal enzyme that hydrolyzes sulfate groups from the glycosaminoglycans keratan sulfate and chondroitin-6-sulfate; SUBCELLULAR LOCATION lysosome; homodimer; formylglycine (3-oxoalanine) modification of Cys79 critical for activity; deficiency causes MPS4A (Morquio A).