3.1.6.8: cerebroside-sulfatase
This is an abbreviated version!
For detailed information about cerebroside-sulfatase, go to the full flat file.
Word Map on EC 3.1.6.8
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3.1.6.8
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metachromatic
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leukodystrophy
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sulfatide
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medicine
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lysosomal
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asa
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demyelinate
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sural
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pseudodeficiency
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nitrocatechol
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sulfatases
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molecular biology
- 3.1.6.8
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metachromatic
- leukodystrophy
- sulfatide
- medicine
- lysosomal
- asa
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demyelinate
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sural
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pseudodeficiency
- nitrocatechol
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sulfatases
- molecular biology
Reaction
Synonyms
ARS, ARSA, arylsulfatase A, arylsulfatase E, arylsulfatase-A, AS-A, ASA, cerebroside sulfatase, cerebroside sulfate sulfatase, Cerebroside-sulfatase, sulfatase, cerebroside
ECTree
3.1.6.8 cerebroside-sulfataseAdvanced search results
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Engineering on EC 3.1.6.8 - cerebroside-sulfatase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
A212P
naturally occuring ARSA polymorphism, causes a severe peripheral neuropathy phenotype
C168stop
naturally occuring ARSA polymorphism, causes a severe peripheral neuropathy phenotype
C300F
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the sequence alteration is found in a patient with metachromatic leukodystrophy, the mutant strongly interferes with the octamerization process of enzyme but not with its dimerization capacity
C500F
C69A
The inactive mutant in complex with p-nitrocatechol sulfate mimics a reaction intermediate during sulfate ester hydrolysis by the active enzyme, without the covalent bond to the key side-chain C-alpha-formylglycine
C69S
D407fs
naturally occuring ARSA polymorphism, causes a severe peripheral neuropathy phenotype
E253K/T391S
mutations contribute to sum of the enzyme activity reduction ascribed to each mutation
E307K
naturally occuring ARSA polymorphism, causes a mild peripheral neuropathy phenotype
E382Q
H138D
naturally occuring ARSA polymorphism, causes a mild peripheral neuropathy phenotype
H231Q
mutation identified in three patients belonging to a consanguineous family with late-infantile metachromatic leukodystrophy disorder MLD. The mutation leads to changes in the pre-mRNA secondary structure and in the ArsA protein structure
K302A
K367A
K393A
K393A/K395G
K393A/K395H
K433A
K457G
K457R
K457S
K463Q
K463R
L52P
naturally occuring ARSA polymorphism, causes a severe peripheral neuropathy phenotype
N158Q/N350Q
N350S
P425T
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the sequence alteration is found in a patient with metachromatic leukodystrophy, the mutant displays a modest reduction of oligomerization process but not with its dimerization capacity
P426L/N350S/96A>G
mutations contribute to sum of the enzyme activity reduction ascribed to each mutation
R288H
R288H/R496H/N350S
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about 38% reduction of enzyme activity in comparison to wild-type enzyme, no additive effect of the various amino acid substitutions is found in vitro
R496H
S406G
naturally occuring ARSA polymorphism, causes a severe peripheral neuropathy phenotype
T304M
naturally occuring ARSA polymorphism, causes a severe peripheral neuropathy phenotype
C69A
site-directed mutagenesis, the mnutant shows abolished enzyme activity and only residual binding to thr sulfoglycolipid substrate
C69A/K123A/K302A
site-directed mutagenesis, the mutant shows abolished substrate binding and activity
additional information
C500F
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about 8% reduction of enzyme activity in comparison to wild-type enzyme. Mutation found in a patient with metachromatic leukodystrophy
C69S
the mutant is able to bind covalently to the substrate and hydrolyse it, but is unable to release the resulting sulfate
C69S
present at significantly higher levels in both conditioned media and within the cell when compared with wild type
E382Q
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complete loss of enzyme activity in comparison to wild-type enzyme in vitro
E382Q
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complete loss of enzyme activity in comparison to wild-type enzyme in vitro. Mutation found in a patient with metachromatic leukodystrophy
K302A
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34% of the activity of wild-type enzyme when expressed in BHK cells. Mutation has no effect on distribution of the enzyme activity between cell and medium
K367A
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60% of the activity of wild-type enzyme when expressed in BHK cells. Mutation has no effect on distribution of the enzyme activity between cell and medium. 106% of the mannose-phosphorylation of the wild-type enzyme
K393A
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39% of the activity of wild-type enzyme when expressed in BHK cells. Mutation has no effect on distribution of the enzyme activity between cell and medium. 123% of the mannose-phosphorylation of the wild-type enzyme
K393A/K395G
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35% of the activity of wild-type enzyme when expressed in BHK cells. Mutation has no effect on distribution of the enzyme activity between cell and medium
K393A/K395H
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30% of the activity of wild-type enzyme when expressed in BHK cells. Mutation has no effect on distribution of the enzyme activity between cell and medium
K433A
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102% of the activity of wild-type enzyme when expressed in BHK cells. Mutation has no effect on distribution of the enzyme activity between cell and medium. 95% of the mannose-phosphorylation of the wild-type enzyme
K457G
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7.5% of the activity of wild-type enzyme when expressed in BHK cells. Mutation leads to an increase of enzyme activity in the medium to about 60% of total activity compared to 35% of the wild-type enzyme. 31% of the mannose-phosphorylation of the wild-type enzyme. Mutation affects phosphorylation of oligosaccharide Asn350 to a greater extent than that of oligosaccharide Asn158
K457R
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45% of the activity of wild-type enzyme when expressed in BHK cells. Mutation leads to an increase of enzyme activity in the medium to about 60% of total activity compared to 35% of the wild-type enzyme. 33% of the mannose-phosphorylation of the wild-type enzyme. Mutation affects phosphorylation of oligosaccharide Asn350 to a greater extent than that of oligosaccharide Asn158
K457S
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25% of the activity of wild-type enzyme when expressed in BHK cells. 50% of the mannose-phosphorylation of the wild-type enzyme. Mutation leads to an increase of enzyme activity in the medium to about 65% of total activity compared to 35% of the wild-type enzyme. 50% of the mannose-phosphorylation of the wild-type enzyme. Mutation affects phosphorylation of oligosaccharide Asn350 to a greater extent than that of oligosaccharide Asn158
K463Q
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14% of the activity of wild-type enzyme when expressed in BHK cells. Mutation leads to an decrease of enzyme activity in the medium to about 25% of total activity compared to 35% of the wild-type enzyme
K463R
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39% of the activity of wild-type enzyme when expressed in BHK cells. 31% of the mannose-phosphorylation of the wild-type enzyme. Mutation leads to an decrease of enzyme activity in the medium to about 25% of total activity compared to 35% of the wild-type enzyme
N158Q/N350Q
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43% of the activity of wild-type enzyme when expressed in BHK cells. Mutation leads to an increase of enzyme activity in the medium to about 25% of total activity compared to 75% of the wild-type enzyme
N350S
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about 15% reduction of enzyme activity in comparison to wild-type enzyme in vitro
N350S
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about 15% reduction of enzyme activity in comparison to wild-type enzyme in vitro, mutation found in a patient with metachromatic leukodystrophy
R288H
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about 40% reduction of enzyme activity in comparison to wild-type enzyme in vitro
R288H
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about 40% reduction of enzyme activity in comparison to wild-type enzyme in vitro, mutation found in a patient with metachromatic leukodystrophy
R496H
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about 15% reduction of enzyme activity in comparison to wild-type enzyme in vitro
R496H
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about 15% reduction of enzyme activity in comparison to wild-type enzyme in vitro, mutation found in a patient with metachromatic leukodystrophy
additional information
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R288H, N350S and R496H are sequence alterations found in a patient with metachromatic leukodystrophy. W124ter mutation, which leads to a truncated enzyme and the mutations E382Q and C500F are found in an other patient.
additional information
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only substitution of Lys457 causes a reduction of phosphorylation to 33% and increases secretion of the mutant enzyme
additional information
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R288H, N350S and R496H are sequence alterations found in a patient with metachromatic leukodystrophy. W124ter mutation, which leads to a truncated enzyme and the mutations E382Q and C500F are found in an other patient
additional information
study of disease-causing mutations, severe phenotype of this patient depends not only on the two disease-causing mutations, but also to some extent on the pseudodeficiency mutations
additional information
the frameshift mutations g.445_446dupG and g.2590_2591dupC are associated with metachromatic leukodystrophy and lead 0.3% or 10% of wild type ARSA activity, respectively
additional information
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the frameshift mutations g.445_446dupG and g.2590_2591dupC are associated with metachromatic leukodystrophy and lead 0.3% or 10% of wild type ARSA activity, respectively
additional information
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secretion and half-life of wild-type enzyme are reduced upon co-expression of defective P377L-pdASA
additional information
characterization of pathogenic variants c.98T > C, c.195delC, c.229G > C, c.545C > G, c.674A > G, c.852T > A, and c.1274A > G, which were found when sequencing a cohort of 31 German metachromatic leukodystrophy families. Upon expression in immortalized, human multipotent mesenchymal stromal cells prepared from a patient deficient in ARSA activity, the seven mutants show ARSA activity of less than 10% when compared with wild type
additional information
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sperm from AS-A null mice show a significant delay in cumulus oocyte complex dispersion, compared with wild-type sperm
additional information
coating culture plates with recombinant mouse ArsA stimulates adhesion of human microvascular endothelial cells to the plate followed by the formation of cell protrusions as well as lamellipodia
