Components and proteolytic processing sites of arylsulfatase B from human placenta

Background: Human sulfatases play key roles in physiology and cause numerous pathological conditions upon deficiency/misregulation. Results: ARSK is ubiquitously expressed, localizes to lysosomes, and shows arylsulfatase activity at acidic pH. Conclusion: ARSK is a novel lysosomal sulfatase acting on a ubiquitous substrate. Significance: ARSK functions in lysosomal degradation, possibly of glycosaminoglycans, and, in all probability, is associated with a non-classified lysosomal storage disorder.

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“…arylsulfatase B (N-acetylgalactosamine-4-sulfatase) (36,37). In the case of ARSK, we obtained evidence for FIGURE 5.…”

Section: Discussionmentioning

confidence: 59%

Arylsulfatase K, a Novel Lysosomal Sulfatase

Wiegmann

Westendorf

Kalus

et al. 2013

Journal of Biological Chemistry

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“…The isolation and characterization of human ARSB cDNA [5,6] and partial elucidation of the gene structure [7] have allowed the identification of causative molecular defects. Human ARSB is 209 kb long (genome.ucsc.edu), comprising 8 exons ranging in size from 71 to 885 bp, and the nascent polypeptide has 533 amino acids [8] . Some 140 ARSB mutations have been described so far, and a number of polymorphisms have also been identified in the gene sequence [9,10] .…”

mentioning

confidence: 99%

A Community-Based Study of Mucopolysaccharidosis Type VI in Brazil: The Influence of Founder Effect, Endogamy and Consanguinity

Costa-Motta¹,

Bender

Acosta³

et al. 2014

Hum Hered

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Mucopolysaccharidosis type VI (MPS VI - Maroteaux-Lamy syndrome) is a globally rare lysosomal storage disease caused by a deficiency of arylsulfatase B. However, in Monte Santo, a poor and isolated rural region in Northeast Brazil with large family sizes and high rates of community endogamy and parental consanguinity (α = 0.00483), 9 living and 4 now deceased individuals in 11 kindreds have been diagnosed with MPS VI, all with the same p.H178L missense founder mutation. A further 33 deceased persons have been identified by family members as exhibiting the disease phenotype. Detailed pedigrees were constructed for the 13 genomically confirmed MPS VI patients, with blood samples collected from 236 unaffected family members to determine the prevalence of the p.H178L mutation. A total of 98 (20.8%) mutant alleles and 374 (79.2%) normal alleles were identified, with 41.5% of the individuals heterozygous for the p.H178L mutation and 58.5% homozygous for the normal allele. A significant number of other family members with a 50 or 25% chance of being heterozygous for the p.H178L mutation were unavailable for testing. The data indicate a compelling case for community-based neonatal screening in conjunction with further initiatives among MPS VI family members to promote genetic education and genetic counselling.

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“…The 57 kDa species is cleaved into an amino-terminal 43 kDa species, a central 7 kDa species, and a carboxyl-terminal 8 kDa species during transport to, and residence within, the lysosome. The 7 and 8 kDa species are disulfide linked to the 43 kDa species [Kobayashi et al, 1992]. Attempts to correlate disease severity with residual 4S activity or 4S catalytic capacity in patient fibroblasts, or with dermatan sulfate levels in patient urine have been partially successful [Hopwood and Elliott, 1985;Brooks et al, 1991;Brooks, 1993].…”

Section: Introductionmentioning

confidence: 98%

Mucopolysaccharidosis type VI: Structural and clinical implications of mutations in N-acetylgalactosamine-4-sulfatase

Litjens

Hopwood

2001

Hum. Mutat.

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Mucopolysaccharidosis type VI (MPS-VI) is an autosomal recessive lysosomal storage disorder caused by the deficiency of N-acetylgalactosamine-4-sulfatase (4S; or ARSB). Mutations in the 4S gene are responsible for 4S deficiency, which leads to the intralysosomal storage of partially degraded glycosaminoglycans, dermatan sulfate, and chondroitin 4-sulfate. To date, a total of 45 clinically relevant mutations have been identified in the human 4S gene. Missense mutations are the largest group, with 31 identified mutations. Nonsense mutations and small insertions or deletions comprise the remainder, with seven mutations each. Six polymorphisms have also been reported: two amino acid substitutions and four silent transitions. Mapping of the missense mutations onto the 4S structure shows that they are distributed throughout the three subunits of the mature 4S polypeptide. Mutations have been identified in active site residues, in residues adjacent to the active site, in potential substrate binding residues, in residues exposed on the surface, and in residues buried within the protein core. Missense mutations have also been identified in disulfide crosslinks. Molecular modeling of MPS-VI mutations onto the 4S structure suggests that the majority cause 4S deficiency via destabilization and the consequent reduction of 4S protein concentration. The vast majority of MPS-VI mutant alleles are either unique to a patient or are present in a small number of patients. So far, no common mutations have been described. Therefore, screening of the general population for MPS-VI alleles will be difficult.

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Components and proteolytic processing sites of arylsulfatase B from human placenta

Cited by 18 publications

References 23 publications

Arylsulfatase K, a Novel Lysosomal Sulfatase

Arylsulfatase K, a Novel Lysosomal Sulfatase

A Community-Based Study of Mucopolysaccharidosis Type VI in Brazil: The Influence of Founder Effect, Endogamy and Consanguinity

Mucopolysaccharidosis type VI: Structural and clinical implications of mutations in N-acetylgalactosamine-4-sulfatase

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