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J Biol Chem. 2013 Oct 18;288(42):30019-28. doi: 10.1074/jbc.M113.499541. Epub 2013 Aug 28.

Arylsulfatase K, a novel lysosomal sulfatase.

Author information

1
From the Department of Chemistry, Biochemistry I, Bielefeld University, 33615 Bielefeld, Germany and.

Abstract

The human sulfatase family has 17 members, 13 of which have been characterized biochemically. These enzymes specifically hydrolyze sulfate esters in glycosaminoglycans, sulfolipids, or steroid sulfates, thereby playing key roles in cellular degradation, cell signaling, and hormone regulation. The loss of sulfatase activity has been linked to severe pathophysiological conditions such as lysosomal storage disorders, developmental abnormalities, or cancer. A novel member of this family, arylsulfatase K (ARSK), was identified bioinformatically through its conserved sulfatase signature sequence directing posttranslational generation of the catalytic formylglycine residue in sulfatases. However, overall sequence identity of ARSK with other human sulfatases is low (18-22%). Here we demonstrate that ARSK indeed shows desulfation activity toward arylsulfate pseudosubstrates. When expressed in human cells, ARSK was detected as a 68-kDa glycoprotein carrying at least four N-glycans of both the complex and high-mannose type. Purified ARSK turned over p-nitrocatechol and p-nitrophenyl sulfate. This activity was dependent on cysteine 80, which was verified to undergo conversion to formylglycine. Kinetic parameters were similar to those of several lysosomal sulfatases involved in degradation of sulfated glycosaminoglycans. An acidic pH optimum (~4.6) and colocalization with LAMP1 verified lysosomal functioning of ARSK. Further, it carries mannose 6-phosphate, indicating lysosomal sorting via mannose 6-phosphate receptors. ARSK mRNA expression was found in all tissues tested, suggesting a ubiquitous physiological substrate and a so far non-classified lysosomal storage disorder in the case of ARSK deficiency, as shown before for all other lysosomal sulfatases.

KEYWORDS:

ARSK; Arylsulfatase K; Enzyme Kinetics; Enzyme Processing; Lysosomal Glycoproteins; Lysosomal Storage Disease; Lysosomes; Protein Sorting; Sulfatase

PMID:
23986440
PMCID:
PMC3798471
DOI:
10.1074/jbc.M113.499541
[Indexed for MEDLINE]
Free PMC Article

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