Information on EC 3.1.6.8 - cerebroside-sulfatase

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The expected taxonomic range for this enzyme is: Metazoa

EC NUMBER
COMMENTARY hide
3.1.6.8
-
RECOMMENDED NAME
GeneOntology No.
cerebroside-sulfatase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
a cerebroside 3-sulfate + H2O = a cerebroside + sulfate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of sulfuric ester
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Sphingolipid metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
cerebroside-3-sulfate 3-sulfohydrolase
Hydrolyses galactose-3-sulfate residues in a number of lipids. Also hydrolyses ascorbate 2-sulfate and many phenol sulfates.
CAS REGISTRY NUMBER
COMMENTARY hide
9068-68-2
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
cnidaria
-
-
Manually annotated by BRENDA team
Blaberus fuscus
arthropoda
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
molusca
-
-
Manually annotated by BRENDA team
Lima inflata
molusca
-
-
Manually annotated by BRENDA team
annelida
-
-
Manually annotated by BRENDA team
arthropoda
-
-
Manually annotated by BRENDA team
echinodermata
-
-
Manually annotated by BRENDA team
golden Hamster; hamster
-
-
Manually annotated by BRENDA team
molusca
-
-
Manually annotated by BRENDA team
molusca
-
-
Manually annotated by BRENDA team
porifera
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
additional information
-
heteromerization of wild-type and misfolded endoplasmic reticulum-degraded arylsulfatase A polypeptides affects the quality control of wild-type arylsulfatase A subunits. Within a heteromer, the misfolded subunit exerts a dominant negative effect on the wild-type subunit. Mechanism, overview
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1-naphthyl sulfate + H2O
1-naphthol + sulfate
show the reaction diagram
-
-
-
-
?
1-O-alkyl-2-O-acyl-3-(beta-3'-sulfogalactosyl)glycerol + H2O
1-O-alkyl-2-O-acyl-3-O-(beta-galactosyl)glycerol + sulfate
show the reaction diagram
1-O-alkyl-2-O-acyl-3-O-(beta-D-galactopyranoside-3'-sulfate)-glycerol + H2O
1-O-alkyl-2-O-acyl-3-O-beta-D-galactopyranoside-glycerol + sulfate
show the reaction diagram
-
-
-
-
?
1-O-hexadecyl-2-O-hexadecanoyl-3-O-(beta-3'-sulfogalactosyl)glycerol + H2O
1-O-hexadecyl-2-O-hexadecanoyl-3-O-(beta-galactosyl)glycerol + sulfate
show the reaction diagram
-
-
-
-
?
2-hydroxy-5-nitrophenyl sulfate + H2O
2-hydroxy-5-nitrophenol + sulfate
show the reaction diagram
2-hydroxyphenyl sulfate + H2O
2-hydroxyphenol + sulfate
show the reaction diagram
-
-
-
-
?
2-naphthyl sulfate + H2O
2-naphthol + sulfate
show the reaction diagram
-
-
-
-
?
2-nitropyridyl 3-sulfate + H2O
2-nitropyridin-3-ol + sulfate
show the reaction diagram
-
-
-
-
?
3-nitrophenyl sulfate + H2O
3-nitrophenol + sulfate
show the reaction diagram
-
-
-
-
?
4-nitrocatechol sulfate + H2O
4-nitrocatechol + sulfate
show the reaction diagram
4-nitrophenyl sulfate + H2O
4-nitrophenol + sulfate
show the reaction diagram
5,6,7,8-tetrahydro-2-naphthyl sulfate + H2O
5,6,7,8-tetrahydro-2-naphthol + sulfate
show the reaction diagram
-
-
-
-
?
ascorbate 2-sulfate + H2O
ascorbate + sulfate
show the reaction diagram
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
cerebroside 3-sulphate + H2O
cerebroside + sulfate
show the reaction diagram
-
the enzyme catalyzes the first step in the degradation of the glycolipid cerebroside sulfate
-
?
chondroitin sulfate B + H2O
sulfate
show the reaction diagram
-
-
-
-
?
dehydroisoandrosterone sulfate + H2O
dehydroisoandrosterone + sulfate
show the reaction diagram
-
-
-
-
?
estriol 3-sulfate + H2O
estriol + sulfate
show the reaction diagram
-
-
-
-
?
estrone 3-sulfate + H2O
estrone + sulfate
show the reaction diagram
-
-
-
-
?
galactose(3-sulfate)beta1-1'(N-2-hydroxy-acyl)sphingosine + H2O
galactose beta1-1'(N-2-hydroxy-acyl)sphingosine + sulfate
show the reaction diagram
-
-
-
-
?
hyaluronan + H2O
?
show the reaction diagram
-
-
-
-
?
lysoseminolipid sulfate + H2O
lysoseminolipid + sulfate
show the reaction diagram
-
deacylated seminolipid
-
-
?
methylumbelliferyl sulfate + H2O
methylumbelliferone + sulfate
show the reaction diagram
N-acyl-1-O-(beta-3-sulfogalactosyl)sphingosine + H2O
(N-acyl-1-O-galactosyl) sphingosine + sulfate
show the reaction diagram
-
sulfosphingolipids
-
-
?
N-lissamine rhodaminyl-(12-aminododecanoyl)cerebroside 3-sulfate + H2O
?
show the reaction diagram
-
-
-
-
?
nitrocatechol sulfate + H2O
nitrocatechol + sulfate
show the reaction diagram
p-nitrocatechol sulfate + H2O
p-nitrocatechol + sulfate
show the reaction diagram
phenanthryl sulfate + H2O
phenanthrol + sulfate
show the reaction diagram
-
-
-
-
?
phenyl sulfate + H2O
phenol + sulfate
show the reaction diagram
-
-
-
-
?
psychosine sulfate + H2O
psychosine + sulfate
show the reaction diagram
-
deacylated sulphatide
-
-
?
pyridyl 3-sulfate + H2O
pyridol + sulfate
show the reaction diagram
-
-
-
-
?
pyridyl 4-sulfate + H2O
pyridol + sulfate
show the reaction diagram
-
-
-
-
?
seminolipid + H2O
galactolipid + sulfate
show the reaction diagram
-
-
-
-
?
sulfogalactosylceramide + H2O
?
show the reaction diagram
sulfogalactosylglycerolipid + H2O
?
show the reaction diagram
tyrosine O-sulfate + H2O
tyrosine + sulfate
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
cerebroside 3-sulphate + H2O
cerebroside + sulfate
show the reaction diagram
-
the enzyme catalyzes the first step in the degradation of the glycolipid cerebroside sulfate
-
?
sulfogalactosylceramide + H2O
?
show the reaction diagram
sulfogalactosylglycerolipid + H2O
?
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
stimulates at 20 mM
Cl-
-
activation of milt plasma arylsulfatase A is increased up to 78% after treatment with 160 mM NaCl, activation of spermatozoon arylsulfatase A is increased up to 147% after treatment with 160 mM NaCl
Mg2+
-
stimulates at 20 mM
ZnCl2
-
stimulates at 20 mM
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4-methylumbelliferyl phosphate
AgNO3
-
50% decreased activity in milt plasma with 60 nM AgNO3 and 50% decreased activity in spermatozoon with 4 nM AgNO3
anti-AS-A IgG
-
dispersion of cumulus layers of cumulus oocyte complexes does not occurr in co-incubates with anti-AS-A IgG treated sperm and in the presence of apigenin
-
ascorbate
barium acetate
-
-
Cd2+
-
-
ceramide
-
inhibition or activation depends on substrate
cerebroside
-
inhibition or activation depends on substrate
Cerebroside 6-sulfate
-
-
cerebroside sulfate
estradiol
-
significantly declines ASA in myoepithelial, MCF7, and T47D cells
estrone
-
significant declines ASA in myoepithelial, MCF7, and T47D cells
ethanol
-
decreases ASA activity levels in the liver, but not in the cerebral cortex and kidney
Galactose 3-sulfate
-
-
Galactose 6-sulfate
-
-
H2SO4
-
50% decreased activity in milt plasma with 25 mM H2SO4 and 26% decreased activity in spermatozoon with 25 mM H2SO4
H3PO4
-
56% decreased activity in milt plasma with 1 mM H3PO4 and 43% decreased activity in spermatozoon with 1 mM H2SO4
Hg2+
-
-
hydrazine
hydroxylamine
N-ethylmaleimide
-
no inhibition at pH 5.5, but at pH 5.0
Na+
-
enzymatic activity is inhibited at NaCl concentrations exceeding 20 mM, at 50 and 200 mM the rate of sulfatide hydrolysis is diminished by about 50 and 75%, respectively
nitrocatechol sulfate
p-hydroxymercuribenzoate
phophatidylinositol
-
inhibition or activation depends on substrate
phosphate
-
competitive inhibitor
phosphatidylcholine
-
inhibition or activation depends on substrate
psychosine
-
inhibition or activation is substrate-dependent
Semicarbazide
-
-
Sn2+
-
-
sphingomyelin
-
inhibition or activation depends on substrate
sulfite
-
competitive inhibitor
thiol reagents
-
-
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Bile salts
bis(monoacylglycero) phosphate
-
at a relative concentration of 30 mol% the lipid stimulates the reaction rate by a factor of 3.4
-
ceramide
-
inhibition or activation depends on substrate
cerebroside
-
inhibition or activation depends on substrate
dolichol
-
at a relative concentration of 30 mol% the lipid stimulates the reaction rate by a factor of 2.7
phosphatidic acid
-
at a relative concentration of 30 mol% the lipid stimulates the reaction rate by a factor of 3.1
phosphatidylcholine
-
inhibition or activation depends on substrate
Protein factor
psychosine
-
inhibition or activation is substrate-dependent
saposin B
-
small activator protein to solubilize hydrophobic substrates
-
sphingomyelin
-
inhibition or activation depends on substrate
taurodeoxycholate
ZnCl2
-
-
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
15.9
1-naphthyl sulfate
-
-
0.2 - 0.5
1-O-Alkyl-2-O-acyl-3-O-(beta-D-galactopyranoside-3'-sulfate)-glycerol
-
-
0.47
2-hydroxy-5-nitrophenyl sulfate
-
-
38
2-hydroxyphenyl sulfate
-
-
6.5
2-nitrophenyl sulfate
-
-
4.4
2-nitropyridyl 3-sulfate
-
-
77
3-nitrophenyl sulfate
-
-
4
4-methylumbelliferone sulfate
-
-
8
4-Methylumbelliferyl sulfate
-
-
0.43 - 6.7
4-nitrocatechol sulfate
53
4-nitrophenyl sulfate
-
-
63
5,6,7,8-tetrahydro-2-naphthyl sulfate
-
-
23
Ascorbate 2-sulfate
-
at pH 5.6
0.1 - 3.3
cerebroside 3-sulfate
0.06 - 0.2
cerebroside sulfate
53
Naphthyl sulfate
-
-
0.8
nitrocatechol sulfate
-
-
0.175 - 1
p-nitrocatechol sulfate
3
p-nitrophenol sulfate
-
-
9.5
phenanthryl sulfate
-
-
310
phenyl sulfate
-
-
31
pyridyl 3-sulfate
-
-
0.76
pyridyl 4-sulfate
-
-
31.8
Tyrosine O-sulfate
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.817
4-Methylumbelliferyl sulfate
Homo sapiens
-
-
16.8
4-nitrocatechol sulfate
Homo sapiens
-
-
1.45
cerebroside sulfate
Homo sapiens
-
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.000028
-
endogenous activity in HeLa cells
0.00048
-
arylsulfatase fused with GFP expressed in HeLa cells
0.00086
-
before tamoxifen treatment
0.0009
-
3 months after treatment with 40 mg tamoxifen for one week
0.00096
-
arylsulfatase expressed in HeLa cells
0.00127
-
arylsulfatase tagged with hemagglutinin expressed in HeLa cells
0.0013
-
6 months after treatment with 40 mg tamoxifen for one week
0.001393
-
healthy female, comparison of activities at different ages
0.001593
-
female with benign breast disease, comparison of activities at different ages
0.0018
-
in serum
0.00208
-
-
0.002233
-
female with breast cancer, comparison of activities at different ages
0.0039
-
in liver
0.0148
-
arylsulfatase A co-expressed with formylglycine-generating enzyme, in liver
0.0272
-
arylsulfatase A co-expressed with formylglycine-generating enzyme, in serum
1.5
-
nitrocatechol sulfate
3.633
-
spermatozoon, 0.5 M acetate buffer, pH 4.9, 37C
4.316
-
milt plasma, 0.5 M acetate buffer, pH 4.9, 37C
5
-
degraded enzyme
24
-
66 kDa form
42
-
nitrocatechol sulfate
60
-
purified enzyme, 66 kDa form
69.2
-
nitrocatechol sulfate
135
-
nitrocatechol sulfate
1393
-
healthy woman, comparison of activities at different ages
1593
-
woman with benign breast disease, comparison of activities at different ages
2233
-
woman with breast cancer, comparison of activities at different ages
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.3
-
narrow pH optimum around pH 4.3
4.5
-
-
4.5 - 4.8
-
-
4.6 - 5
-
cholate-activated
4.7
-
cerebroside 3-sulfate
4.8
-
ascorbate 2-sulfate
4.9
-
in milt plasma
5
-
in spermatozoon
5 - 5.5
-
pH optimum depends on time of incubation, 5-20 min: pH 5.5, 30-90 min: pH 5.0
5 - 5.5
5.2
-
4-methylumbelliferyl sulfate
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
3.75 - 4.75
-
desulfation activity is less than half-maximum at pH values below pH 3.75 and above pH 4.75
4 - 5
-
pH 4, pH 5: circa 20% of activity maximum
4 - 5.8
-
pH 4, pH 5.8: circa 20% of activity maximum, 10 mM sodium formate buffer
4.1 - 4.8
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
40
-
milt plasma and spermatozoon
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
immunocytochemistry of the epididymis reveals the enzyme in narrow and apical cells in the initial segment and in clear cells in all epididymal region
Manually annotated by BRENDA team
-
highest activity of ASA
Manually annotated by BRENDA team
-
lowest activity of ASA
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
fibroblasts in culture
Manually annotated by BRENDA team
-
; human fibroblasts grown in the presence of lead acetate exhibit a 65% decrease in enzyme protein
Manually annotated by BRENDA team
-
; oral cavity treatment with 7,12-dimethylbenzanthracene increases activity significantly in both sexes. Administration of 7,12-dimethylbenzanthracene plus beta-carotene decreases activity remarkably in female hamsters
Manually annotated by BRENDA team
-
; oral cavity treatment with 7,12-dimethylbenzanthrracene increases activity significantly in both sexes. Administration of 7,12-dimethylbenzanthracene plus beta-carotene decreases activity slightly
Manually annotated by BRENDA team
-
in vas deferens fluid
Manually annotated by BRENDA team
additional information
-
the polypeptide complexes, rather than the monomers, are subject to endoplasmic reticulum quality control and, within a heteromer, the misfolded subunit exerts a dominant negative effect on the wild-type subunit
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
a large portion of the mammalian arylsulfatase A protein exists on the cell surface of vascular endothelial cells
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
54000
-
in the liver samples of control and ethanol treated rats, Western blot analysis
62000
-
gel filtration, Concanavalia ensiformis agglutinin retained protein
63000
-
copurification with beta-galactosidase, both enzymes aggregate into macromolecular complexes at pH 4 and disaggregate at pH 8, SDS-PAGE
65000
-
gel filtration, wheat germ agglutinin retained protein
66000
-
SDS-PAGE
68000
-
gel filtration, total protein extract of capacitated sperm
100000
-
sedimentation equilibrium ultracentrifugation
105000
-
-
107000
-
at pH 7.5
123000
-
gradient SDS-PAGE
130000
-
gel filtration
140000
172000
-
gel-filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 62000, SDS-PAGE
homodimer
-
at neutral pH
homooctamer
-
at acidic pH
monomer
octamer
oligomer
tetramer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
phosphoprotein
-
compared to the degree of mannose-phosphorylation of the wild-type enzyme, the mutant enzyme K457R has 33%, mutant enzyme K457S has 50%, mutant enzyme K457G has 31%, mutant enzyme K433A has 95%, mutant enzyme K367A has 106% and mutant enzyme K393A has 123% of mannose-phosphorylation respectively
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
aldehyde function and metal ion at the active site
-
crystal structure of mutant C69A a nd C69S in complex with p-nitrocatechol sulfate; crystal structure of mutant C69A in complex with p-nitrocatechol sulfate, Protein Data Bank: 1E1Z and 1E2S, and crystal structure of mutant C69S in complex with p-nitrocatechol sulfate, Protein Data Bank: 1E33 and 1E3C
-
crystallisation of enzyme at pH 5.4 in a new monoclinic crystal form, at pH 6.5-6.7, tetragonal crystals are obtained.
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
10 - 40
60
-
t1/2: 7 min
65
-
5 min, no loss of activity
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
4C, addition of dithiothreitol, glutathione, or EDTA reduce storage stability
-
bovine serum albumin stabilizes
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C or 2C, over a week, significant loss of activity
-20C, protein: 1 mg/ml
-
-20C, protein: 1 mg/ml, stable for months
-
0C, 2 months
-
4C, pH 7.5, protein: 0.002 mg/ml, bovine serum albumin, insulin or ribonuclease, 15 days, no loss of activity
-
4C, pH 7.5, protein: 0.002 mg/ml, bovine serum albumin, insulin or ribonuclease, 8 months, 30% loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
by gel filtration
large scale
-
of the recombinant protein
-
partial
recombinant myc-His- or GFP-tagged ArsA by affinity chromatography from culture cell supernatant
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
coexpreesion with mannose 6-phosphate receptor; expression in BHK cells
-
coexpression and secretion of misfolded, enzymatically inactive enzyme with the wild-type enzyme, whose activity is diminished upon coexpression with misfolded ASA polypeptides, in BHK cells
-
expressed in baby hamster kidney cells and CHO cells
-
expressed in CHO cells
-
expression in arylsulfatase A-deficient mice, HEK-293 cells, HeLa cells and COS-7 cells
-
expression in BHK cells
-
expression of wild-type and mutant enzymes in CHO-K1 cells
HSPC cells transduced with increasing doses of lentiviral vectors expressing ARSA under the control of the human PGK promoter (PGK.ARSA.LV). Transgenic mice generated with PGK.ARSA.LV overexpressing the ARSA enzyme
-
human arylsulfatase A tagged with hemagglutinin or GFP cloned in a lentiviral vector, expressed in HeLa cells and mice
-
mutation expressed from allele are examined in heterologous BHK cells
-
overexpression in CHO-K1 cells
-
plasmids containing the wild-type and mutant cDNAs are transiently transfected into BHK cells; wild-type and mutant enzymes transiently transfected into BHK cells
-
recombinant expression in CHO, BHK and HT-1080 cells. High variability of the high-mannose-type N-glycans, which prevail at all glycosylation sites, depending on the culture conditions and the cell line expressing the enzyme, overview
-
recombinant expression of myc-His- or GFP-tagged ArsA, the recombinant protein is secreted into the serum-free medium
the ARSA gene is a small gene located on chromosome 22q13 that spans 8 exons and encodes a 507-aminoacid peptide, it is transcribed into three mRNA species, a major one of 2.1 kb and two less abundant species of 3.7 and 4.8 kb. DNA and amino acid sequence determination and analysis of natural mutants. Recombinant expression in HeLa cells using lentiviral vectors, containing mutated ARSA alleles, the vectors stably integrate into the host genome. expression of mutated alleles in murine ARSA-/- fibroblasts
-
transient expression experiments on COS7 cells transfected with enzyme cDNAs carrying the mutations separately and in the combination found in the patient's alleles; transient expression experiments on COS7 cells transfected with enzyme cDNAs carrying the mutations separately and in the combination found in the patients alleles
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A212P
-
naturally occuring ARSA polymorphism, causes a severe peripheral neuropathy phenotype
A96G
-
mutation contributes to enzyme activity reduction
C168stop
-
naturally occuring ARSA polymorphism, causes a severe peripheral neuropathy phenotype
C300F
-
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
C493F
-
mutant shows 0.7% of wild type ARSA activity
C500F
-
about 8% reduction of enzyme activity in comparison to wild-type enzyme; about 8% reduction of enzyme activity in comparison to wild-type enzyme. Mutation found in a patient with metachromatic leukodystrophy
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
D255H
-
inactive misfolded mutant D255H-ASA
D335V
-
inactive misfolded mutant D335V-ASA
D407fs
-
naturally occuring ARSA polymorphism, causes a severe peripheral neuropathy phenotype
E253K
-
mutation contributes to enzyme activity reduction
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
-
complete loss of enzyme activity in comparison to wild-type enzyme in vitro; complete loss of enzyme activity in comparison to wild-type enzyme in vitro. Mutation found in a patient with metachromatic leukodystrophy
G293C
-
mutant shows 0.5% of wild type ARSA activity
G86D
-
inactive misfolded mutant G86D-ASA
H138D
-
naturally occuring ARSA polymorphism, causes a mild peripheral neuropathy phenotype
K302A
-
34% enzyme activity in comparison to wild-type enzyme; 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
-
60% enzyme activity in comparison to wild-type enzyme; 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
-
39% enzyme activity in comparison to wild-type enzyme; 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% enzyme activity in comparison to wild-type enzyme; 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% enzyme activity in comparison to wild-type enzyme; 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% enzyme activity in comparison to wild-type enzyme; 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% enzyme activity in comparison to wild-type enzyme; 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% enzyme activity in comparison to wild-type enzyme; 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% enzyme activity in comparison to wild-type enzyme; 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% enzyme activity in comparison to wild-type enzyme; 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% enzyme activity in comparison to wild-type enzyme; 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
L52P
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naturally occuring ARSA polymorphism, causes a severe peripheral neuropathy phenotype
N158Q/N350Q
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43% enzyme activity in comparison to wild-type enzyme; 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
P136L
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inactive misfolded mutant P136LASA
P377L
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inactive misfolded mutant P377L-pdASA
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
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mutation contributes to enzyme activity reduction
P426L/N350S/96A>G
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mutations contribute to sum of the enzyme activity reduction ascribed to each mutation
R288H
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about 40% reduction of enzyme activity in comparison to wild-type enzyme in vitro; about 40% reduction of enzyme activity in comparison to wild-type enzyme in vitro, mutation found in a patient with metachromatic leukodystrophy
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
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about 15% reduction of enzyme activity in comparison to wild-type enzyme in vitro; about 15% reduction of enzyme activity in comparison to wild-type enzyme in vitro, mutation found in a patient with metachromatic leukodystrophy
S406G
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naturally occuring ARSA polymorphism, causes a severe peripheral neuropathy phenotype
T201C
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inactive misfolded mutant T201C-ASA
T275M
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inactive misfolded mutant T275M-ASA
T304M
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naturally occuring ARSA polymorphism, causes a severe peripheral neuropathy phenotype
T391S
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mutation contributes to enzyme activity reduction
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
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
molecular biology
Ars can be very useful for clarifying the mechanisms underpinning syndromes caused by the deficiency of the function of Ars genes