"The G137V mutation did not affect the synthesis but severely reduced the stability of the arylsulfatase B precursor."

"the majority of the mutant precursor was degraded presumably in a compartment proximal to the trans Golgi network and only a small amount escaped to the lysosomes"

"accounting for the low residual enzyme activity in fibroblasts of a patient with the juvenile form of the disease."

"The sulfatase enzymes, N-acetylgalactosamine-4-sulfatase (arylsulfatase B (ASB)) and galactose-6-sulfatase (GALNS) hydrolyze sulfate groups of CS."

"Following silencing of ASB or GALNS, total sGAG, C4S, and CS increased significantly."

"Following overexpression of ASB or GALNS, total sGAG, C4S, and CS declined significantly."

"mRNA expression of core proteins of the CS-containing proteoglycans, syndecan-1 and decorin, was significantly up-regulated following overexpression of ASB"

"Arylsulfatase B (ASB; N-acetylgalactosamine-4-sulfatase; 4-sulfatase; ARSB) is the enzyme that removes 4-sulfate groups from N-acetylgalactosamine 4-sulfate, which combines with glucuronate to form the disaccharide unit of chondroitin-4-sulfate (C4S)."

"In the T84 cell line, derived from lung metastasis of malignant colonic epithelial cells, the activity of ASB, as well as steroid sulfatase, arylsulfatase A, and galactose-6-sulfatase, were significantly less than in normal, primary colonic epithelial cells"

"When ASB expression was silenced by siRNA in the NCM460 cells, MMP9 secretion increased to over 3 times the basal level, activated RhoA increased * 85%, and cell migration increased * 52%."

"Following overexpression of ASB, MMP9 declined 51%, activated RhoA declined * 51%, and cell migration decreased * 37%."

"These findings demonstrate marked effects of ASB expression on the migratory activity of colonic epithelial cells, activated RhoA, and MMP9, and suggest a potential vital role of ASB, due to its impact on chondroitin sulfation, on determination of the invasive phenotype of colonic epithelial cells."

"The deduced amino acid sequence of 533 amino acids contains a 41-amino acid N-terminal signal peptide and a mature polypeptide of 492 amino acid residues."

"Pulse-chase labeling showed that ASB was synthesized and secreted as a 64-kDa precursor and processed to a 47-kDa mature form in BHK cells."

"The 47-kDa ASB form was located in dense lysosomes. Transport of ASB to the lysosomes was accomplished in a mannose 6-phosphate receptor-dependent manner."

"Deduced amino acid sequences of human arylsulfatase A, human ASB, human steroid sulfatase, human glucosamine-6-sulfatase, and an arylsulfatase from sea urchin showed a substantial degree of similarity suggesting that they arose from a common ancestral gene and are members of an arylsulfatase gene family."

"In pooled EPS-urine exosome samples, ~900 proteins were detected [including ARSB]"

"Arylsulfatase B (ARSB) hydrolyses sulfate from N-acetylgalactosamine 4-sulfate units within dermatan sulfate (DS; Gorham & Cantz 1978)"

"The conversion to 3-oxoalanine (formylglycine, FGly) of a cysteine residue in eukaryotes, is critical for catalytic activity"

"Defects in ARSB are the cause of mucopolysaccharidosis type VI (MPSVI) (MIM:253200, also called Maroteaux-Lamy syndrome (Wicker et al. 1991)"

"SUMF1 mediates the oxidation of cysteine to formylglycine, producing active arylsulfatases"

"SUMF1 mediates the oxidation of cysteine to formylglycine, producing active arylsulfatases [during biosynthesis]"

"Arylsulfatase B using calcium cofactor (ARSB:Ca2+) hydrolyses sulfate from N-acetylgalactosamine 4-sulfate (or 6-sulfate) units (GalNAc 4-sulfate or GalNAc 6-sulfate) within chondroitin sulfate"

"The conversion to 3-oxoalanine (formylglycine, FGly) of a cysteine residue in eukaryotes, is critical for catalytic activity, based on similarity to the prototypical arylsulfatase ARSA"

"Defective ARSB does not hydrolyse C4S/C6S chains"

"Defective ARSB does not hydrolyse C4S/C6S chains [leading to MPS VI]"

"Exocytosis of azurophil granule lumen proteins"

"Exocytosis of azurophil granule lumen proteins"

"Exocytosis of ficolin-rich granule lumen proteins [ARSB is present]"

"Exocytosis of ficolin-rich granule lumen proteins"

"Defective ARSB does not hydrolyse DS"

"Defective ARSB does not hydrolyse DS [contributing to MPS VI pathology]"

"Removes sulfate groups from chondroitin-4-sulfate (C4S) and regulates its degradation"

"Involved in the regulation of cell adhesion, cell migration and invasion in colonic epithelium"

"In the central nervous system, is a regulator of neurite outgrowth and neuronal plasticity, acting through the control of sulfate glycosaminoglycans and neurocan levels"

"COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Note=Binds 1 Ca(2+) ion per subunit."

"The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity."

"DISEASE: Mucopolysaccharidosis 6 (MPS6) [MIM:253200]: A form of mucopolysaccharidosis, a group of lysosomal storage diseases characterized by defective degradation of glycosaminoglycans"

"Primary: ARSB is predominantly a lysosomal enzyme. Extra-lysosomal: Immunohistochemistry and immunofluorescence studies have also detected ARSB at the cell membrane"

"Extracellular matrix remodeling: ARSB influences the composition and turnover of the extracellular matrix, affecting cell adhesion, migration, and invasion"

"Cancer: Reduced ARSB expression is linked to altered proteoglycan expression and tumor progression in prostate and colonic epithelial cells. Acts as a tumor suppressor"

"Neuronal development: In the central nervous system, ARSB regulates neurite outgrowth and neuronal plasticity by controlling sulfate GAG and neurocan levels"

"Enzyme replacement therapy (ERT) with recombinant ARSB is the standard treatment for MPS VI, aiming to reduce GAG accumulation and ameliorate symptoms"

"Arylsulfatase B (ARSB) is a sulfohydrolase that catalyzes the removal of 4-sulfate groups from N-acetylgalactosamine-4-sulfate residues located at the non-reducing end of glycosaminoglycan (GAG) chains. The systematic name of the enzyme is N-acetyl-D-galactosamine-4-sulfate 4-sulfohydrolase (Bond et al., 1997; Valayannopoulos et al., 2010)."

"Notably, ARSB also demonstrates activity against N-acetylglucosamine-4-sulfate as a substrate (Bond et al., 1997). This activity is consistent with the enzyme's ability to act on related 4-sulfated hexosamine residues, though its primary physiological substrates remain the GAG chains of DS and C4S."

"The crystal structure of human ARSB (PDB: 1FSU), solved at 2.5 A resolution, revealed that: Formylglycine (FGly91) is found in a sulfate-modified form (oxo-alanine sulfate ester) in the active site; A divalent calcium ion (Ca2+) is coordinated at the active site and is essential for catalysis; The calcium ion binds directly to the sulfate group of the modified cysteine residue (Bond et al., 1997)"

"The sulfate hydrolysis mechanism proceeds through either an addition-hydrolysis (AH) or transesterification-elimination (TE) pathway, with current evidence favoring the TE mechanism. In this mechanism: The aldehyde of formylglycine becomes hydrated to a gem-diol; One hydroxyl of the gem-diol attacks the substrate sulfur, forming a covalent enzyme-sulfate intermediate; Elimination releases the product and regenerates the aldehyde (Hanson et al., 2004)"

"The mature enzyme of 533 amino acids is generated after cleavage of the signal peptide and is targeted to lysosomes via the mannose-6-phosphate (M6P) receptor pathway (Braulke & Bonifacino, 2009)."

"While primarily a lysosomal enzyme, ARSB also exhibits extra-lysosomal localization. Studies have demonstrated ARSB presence at the plasma membrane and in the extracellular matrix, where it participates in local GAG remodeling (Bhattacharyya et al., 2009)."

"Beyond its housekeeping role in GAG catabolism, ARSB has emerged as a regulator of cellular signaling and gene expression. By controlling the sulfation status of cell-surface and extracellular GAGs, ARSB modulates: Galectin-3 binding: The degree of chondroitin 4-sulfation affects galectin-3 sequestration and release, influencing downstream signaling; SHP-2 phosphatase activity: ARSB activity impacts SHP-2 localization and function (Bhattacharyya et al., 2022)"

"These broader roles suggest ARSB functions as a tumor suppressor, transcriptional mediator, and regulator of cellular signaling beyond its classical lysosomal function."

"Despite lacking detectable sequence similarity, the ARSB active site domain closely resembles that of alkaline phosphatase. The calcium in ARSB superimposes on one of the zinc ions in alkaline phosphatase, and the oxo-alanine sulfate ester superimposes on the phosphate ion in alkaline phosphatase (Bond et al., 1997)"

"Genetic heterogeneity: Over 220 unique ARSB variants have been identified, including Missense variants: 59.5%, Small deletions: 13.5%, Nonsense mutations: 12.0%, Splice site variants: 5.0%"