Information on EC 3.1.6.8 - cerebroside-sulfatase

New: Word Map on EC 3.1.6.8
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Metazoa

EC NUMBER
COMMENTARY
3.1.6.8
-
RECOMMENDED NAME
GeneOntology No.
cerebroside-sulfatase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a cerebroside 3-sulfate + H2O = a cerebroside + sulfate
show the reaction diagram
hydrolyses galactose-3-sulfate residues in a number of lipids, also hydrolyses ascorbate 2-sulfate and many phenol sulfates, enzymes catalyze in addition to reaction of EC 3.1.6.8 also arylsulfatase reaction EC 3.1.6.1
-
a cerebroside 3-sulfate + H2O = a cerebroside + sulfate
show the reaction diagram
hydrolyses galactose-3-sulfate residues in a number of lipids, also hydrolyses ascorbate 2-sulfate and many phenol sulfates, enzymes catalyze in addition to reaction of EC 3.1.6.8 also arylsulfatase reaction EC 3.1.6.1
-
a cerebroside 3-sulfate + H2O = a cerebroside + sulfate
show the reaction diagram
hydrolyses galactose-3-sulfate residues in a number of lipids, also hydrolyses ascorbate 2-sulfate and many phenol sulfates, enzymes catalyze in addition to reaction of EC 3.1.6.8 also arylsulfatase reaction EC 3.1.6.1
-
a cerebroside 3-sulfate + H2O = a cerebroside + sulfate
show the reaction diagram
hydrolyses galactose-3-sulfate residues in a number of lipids, also hydrolyses ascorbate 2-sulfate and many phenol sulfates, enzymes catalyze in addition to reaction of EC 3.1.6.8 also arylsulfatase reaction EC 3.1.6.1
-
a cerebroside 3-sulfate + H2O = a cerebroside + sulfate
show the reaction diagram
hydrolyses galactose-3-sulfate residues in a number of lipids, also hydrolyses ascorbate 2-sulfate and many phenol sulfates, enzymes catalyze in addition to reaction of EC 3.1.6.8 also arylsulfatase reaction EC 3.1.6.1
-
a cerebroside 3-sulfate + H2O = a cerebroside + sulfate
show the reaction diagram
hydrolyses galactose-3-sulfate residues in a number of lipids, also hydrolyses ascorbate 2-sulfate and many phenol sulfates, enzymes catalyze in addition to reaction of EC 3.1.6.8 also arylsulfatase reaction EC 3.1.6.1
-
a cerebroside 3-sulfate + H2O = a cerebroside + sulfate
show the reaction diagram
hydrolyses galactose-3-sulfate residues in a number of lipids, also hydrolyses ascorbate 2-sulfate and many phenol sulfates, enzymes catalyze in addition to reaction of EC 3.1.6.8 also arylsulfatase reaction EC 3.1.6.1
Marthasterias glacialis, Actinia equina, Lima inflata, Blaberus fuscus
-
a cerebroside 3-sulfate + H2O = a cerebroside + sulfate
show the reaction diagram
hydrolyses galactose-3-sulfate residues in a number of lipids, also hydrolyses ascorbate 2-sulfate and many phenol sulfates, enzymes catalyze in addition to reaction of EC 3.1.6.8 also arylsulfatase reaction EC 3.1.6.1
-
a cerebroside 3-sulfate + H2O = a cerebroside + sulfate
show the reaction diagram
A detailed mechanism for sulfate ester cleavage is proposed, involving an aldehyde hydrate as the functional group., a detailed mechanism for sulfate ester cleavage is proposed, involving an aldehyde hydrate as the functional group
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
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.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
arylsulfatase A
-
-
-
-
ASA
-
-
-
-
cerebroside sulfatase
-
-
-
-
cerebroside sulfate sulfatase
-
-
-
-
Cerebroside-sulfatase
-
-
-
-
sulfatase, cerebroside
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9068-68-2
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
cnidaria
-
-
Manually annotated by BRENDA team
Blaberus fuscus
arthropoda
-
-
Manually annotated by BRENDA team
molusca
-
-
Manually annotated by BRENDA team
81 woman, including 28 healthy woman, 29 woman with benign breast disease and 24 patients with primary breast cancer
-
-
Manually annotated by BRENDA team
females with breast cancer
-
-
Manually annotated by BRENDA team
plasmid encoding human arylsulfatase A was expressed in arylsulfatase A-deficient mice, HEK-293 cells, HeLa cells and COS-7 cells
-
-
Manually annotated by BRENDA team
Lima inflata
molusca
-
-
Manually annotated by BRENDA team
arthropoda
-
-
Manually annotated by BRENDA team
golden Hamster; hamster
-
-
Manually annotated by BRENDA team
molusca
-
-
Manually annotated by BRENDA team
male sprague-dawley rats
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
metachromatic leukodystrophy, MLD, is a lysosomal storage disease caused by a deficiency of the lysosomal enzyme arylsulfatase A
malfunction
-
metachromatic leukodystrophy, MLD, is a rare inherited lysosomal storage disorder caused by the deficiency of arylsulfatase A, ARSA
malfunction
P50428
inherited deficiency of arylsulfatase A leads to metachromatic leukodystrophy, MLD, a disease involving demyelination in the central and peripheral nervous systems, with an estimated frequency of 1 in 40000 newborns. Inherited deficiency for arylsulfatase leads to lysosomal storage of sulfated compounds and to serious diseases such as growth retardation, heart failure, and demyelination in the central nervous system
metabolism
-
arylsulfatase A catalyzes the first step in the intralysosomal degradation of the sphingolipid 3-O-sulfogalactosylceramide, briefly called sulfatide
physiological function
-
ARSA is involved in the catabolism of membrane sulfatides into galactosylceramide
physiological function
P50428
ArsA plays a role in the components of the extracellular matrix. ArsA functions as a substrate on which cells adhere and form protrusions. Coating culture plates with recombinant mouse ArsA, rmArsA, stimulates adhesion of human microvascular endothelial cells to the plate followed by the formation of cell protrusions as well as lamellipodia. rmArsA affects the architecture of the cytoskeleton, with a high density of actin filaments localized to peripheral regions of the cells and the extension of bundles of microtubules into the tips of cellular protrusions. rmArsA also affects the distribution pattern of the cell adhesion-associated proteins, integrin alpha2beta1, and paxillin. rmArsA seems to modulate signaling of basic fibroblast growth factor stimulating cytoskeletal rearrangement
metabolism
P50428
ArsA is involved in the modulation of a sort of signaling cascade, which affects the morphology of the cells, by binding to the HSPGs located on the cell surface
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)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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-(beta-3'-sulfogalactosyl)glycerol + H2O
1-O-alkyl-2-O-acyl-3-O-(beta-galactosyl)glycerol + sulfate
show the reaction diagram
-
seminolipid, sulfoglycerolipids
-
-
?
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-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-nitrocatechol sulfate + H2O
4-nitrocatechol + sulfate
show the reaction diagram
-
-
-
-
?
4-nitrocatechol sulfate + H2O
4-nitrocatechol + sulfate
show the reaction diagram
-
artificial substrate, Cys69 is the catalytic residue, and Lys302 and Lys123 act as residues anchoring the sulfate group to the active site, interaction with the enzyme active site, overview
-
-
?
4-nitrocatechol sulfate + H2O
4-nitrocatechol + sulfate
show the reaction diagram
Q8WNR3
artificial substrate, Cys69 is the catalytic residue, and Lys302 and Lys123 act as residues anchoring the sulfate group to the active site, interaction with the enzyme active site, overview
-
-
?
4-nitrophenyl sulfate + H2O
4-nitrophenol + sulfate
show the reaction diagram
-
-
-
-
?
4-nitrophenyl sulfate + H2O
4-nitrophenol + 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
-
-
-
-
?
ascorbate 2-sulfate + H2O
ascorbate + 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-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
-
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
P15289
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
-
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
-
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
Actinia equina, Lima inflata, Blaberus fuscus
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
galactosyl ceramid
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
galactosyl ceramide
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
activity depends on ionic strength, no requirement for activators when acting on cerebroside sulfate
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
3-O-sulfogalactosyl ceramide
galactosyl ceramide
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
the enzyme catalyzes the first step in the degradation of the glycolipid cerebroside sulfate. Accumulation of cerebroside sulfate is responsible for metachromatic leukodystrophy, a severe autosomal recessive inherited disorder. Good correlation between the type of mutation, deficient arylsulfatase A activity and disease severity is recognized
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
the reaction requires saposin B, a non-enzymatic proteinaceous cofactor which presents sulfatide to the catalytic site of arylsulfatase A, desulfation is negligible when Sap B is substituted by Sap A, C, or D
-
-
?
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
-
-
-
-
?
nitrocatechol sulfate + H2O
nitrocatechol + sulfate
show the reaction diagram
-
-
-
-
?
nitrocatechol sulfate + H2O
nitrocatechol + sulfate
show the reaction diagram
-
-
-
-
?
nitrocatechol sulfate + H2O
nitrocatechol + sulfate
show the reaction diagram
-
-
-
-
?
nitrocatechol sulfate + H2O
nitrocatechol + sulfate
show the reaction diagram
-
-
-
-
?
nitrocatechol sulfate + H2O
nitrocatechol + sulfate
show the reaction diagram
-
-
-
-
?
nitrocatechol sulfate + H2O
nitrocatechol + sulfate
show the reaction diagram
-
-
-
-
?
nitrocatechol sulfate + H2O
nitrocatechol + sulfate
show the reaction diagram
-
-
-
-
?
nitrocatechol sulfate + H2O
nitrocatechol + sulfate
show the reaction diagram
-
-
-
-
?
nitrocatechol sulfate + H2O
nitrocatechol + sulfate
show the reaction diagram
-
-
-
-
?
nitrocatechol sulfate + H2O
nitrocatechol + sulfate
show the reaction diagram
-
-
-
-
?
nitrocatechol sulfate + H2O
nitrocatechol + sulfate
show the reaction diagram
Actinia equina, Lima inflata, Blaberus fuscus
-
-
-
-
?
nitrocatechol sulfate + H2O
nitrocatechol + sulfate
show the reaction diagram
-
-
-
-
?
nitrocatechol sulfate + H2O
nitrocatechol + sulfate
show the reaction diagram
-
-
-
-
?
p-nitrocatechol sulfate + H2O
p-nitrocatechol + sulfate
show the reaction diagram
-
-
-
?
p-nitrocatechol sulfate + H2O
p-nitrocatechol + sulfate
show the reaction diagram
-
-
-
?
p-nitrocatechol sulfate + H2O
p-nitrocatechol + sulfate
show the reaction diagram
-
-
-
-
?
p-nitrocatechol sulfate + H2O
p-nitrocatechol + sulfate
show the reaction diagram
-
-
-
-
?
p-nitrocatechol sulfate + H2O
p-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
-
-
-
-
?
sulfatide + H2O
glycerolipid + sulfate
show the reaction diagram
-
-
-
-
?
sulfogalactosylceramide + H2O
?
show the reaction diagram
-
-
-
-
?
sulfogalactosylceramide + H2O
?
show the reaction diagram
Q8WNR3
-
-
-
?
sulfogalactosylceramide + H2O
?
show the reaction diagram
-
Cys69 is the catalytic residue, and Lys302 and Lys123 act as residues anchoring the sulfate group to the active site, interaction with the enzyme active site, overview
-
-
?
sulfogalactosylceramide + H2O
?
show the reaction diagram
Q8WNR3
Cys69 is the catalytic residue, and Lys302 and Lys123 act as residues anchoring the sulfate group to the active site, interaction with the enzyme active site, overview
-
-
?
sulfogalactosylglycerolipid + H2O
?
show the reaction diagram
-
-
-
-
?
sulfogalactosylglycerolipid + H2O
?
show the reaction diagram
-
-
-
-
?
sulfogalactosylglycerolipid + H2O
?
show the reaction diagram
Q8WNR3
-
-
-
?
sulfogalactosylglycerolipid + H2O
?
show the reaction diagram
-
Cys69 is the catalytic residue, and Lys302 and Lys123 act as residues anchoring the sulfate group to the active site, interaction with the enzyme active site, overview
-
-
?
sulfogalactosylglycerolipid + H2O
?
show the reaction diagram
Q8WNR3
Cys69 is the catalytic residue, and Lys302 and Lys123 act as residues anchoring the sulfate group to the active site, interaction with the enzyme active site, overview
-
-
?
tyrosine O-sulfate + H2O
tyrosine + sulfate
show the reaction diagram
-
-
-
-
?
methylumbelliferyl sulfate + H2O
methylumbelliferone + sulfate
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of enzyme
-
-
-
additional information
?
-
-
AS-A has mannose, N-acetylglucosamine and/or sialic acid residues as part of its glycosilation
-
-
-
additional information
?
-
-
is able to disperse cumulus layers of cumulus oocyte complexes. Chondroitin sulfate A, chondroitin sulfate C, ovalbumin and heparan sulfate do not show interaction with AS-A
-
-
-
additional information
?
-
-
substrate binding and docking study, using crystal structures, PDB IDs 1N2K and 1E2S, overview
-
-
-
additional information
?
-
Q8WNR3
substrate binding and docking study, using human crystal structures, PDB IDs 1N2K and 1E2S, overview
-
-
-
additional information
?
-
P50428
recombinant mouse ArsA tightly binds to sulfated polysaccharides
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
P15289
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
Actinia equina, Lima inflata, Blaberus fuscus
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
-
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
galactosyl ceramid
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
-
galactosyl ceramide
-
?
cerebroside 3-sulfate + H2O
cerebroside + sulfate
show the reaction diagram
-
the enzyme catalyzes the first step in the degradation of the glycolipid cerebroside sulfate. Accumulation of cerebroside sulfate is responsible for metachromatic leukodystrophy, a severe autosomal recessive inherited disorder. Good correlation between the type of mutation, deficient arylsulfatase A activity and disease severity is recognized
-
-
?
sulfogalactosylceramide + H2O
?
show the reaction diagram
-
-
-
-
?
sulfogalactosylceramide + H2O
?
show the reaction diagram
Q8WNR3
-
-
-
?
sulfogalactosylglycerolipid + H2O
?
show the reaction diagram
-
-
-
-
?
sulfogalactosylglycerolipid + H2O
?
show the reaction diagram
Q8WNR3
-
-
-
?
cerebroside 3-sulphate + H2O
cerebroside + sulfate
show the reaction diagram
-
the enzyme catalyzes the first step in the degradation of the glycolipid cerebroside sulfate
-
?
additional information
?
-
-
metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of enzyme
-
-
-
additional information
?
-
P50428
recombinant mouse ArsA tightly binds to sulfated polysaccharides
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
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
Mn2+
-
required with taurodeoxycholate or other salt
Mn2+
-
stimulates
ZnCl2
-
stimulates at 20 mM
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-methylumbelliferyl phosphate
-
-
4-methylumbelliferyl phosphate
Q8WNR3
-
Ag+
-
-
Ag+
-
100% inhibition at 0.008 mM or 0.025 mM in seminal plasma or sperm extract
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
-
alone no effect, enhances the inhibition by Cu2+
barium acetate
-
-
Ca2+
-
at 30 mM
Ca2+
-
CaCl2 reduces the reaction rate in the low millimolar range
Cd2+
-
-
ceramide
-
inhibition or activation depends on substrate
cerebroside
-
inhibition or activation depends on substrate
Cerebroside 6-sulfate
-
-
cerebroside sulfate
-
competitive to 1-O-acyl-2-O-alkyl3-O-(beta-D-galactopyranoside-3'-sulfate)glycerol
-
cerebroside sulfate
-
nitrocatechol as substrate
-
Cu2+
-
-
Cu2+
-
-
Cu2+
-
inhibition enhanced in presence of carbonyl reagents or ascorbic acid
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
Fe3+
-
-
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
-
-
hydroxylamine
-
-
Mg2+
-
at 30 mM
Mg2+
-
MgCl2 reduces the reaction rate in the low millimolar range
Mn2+
-
at 30 mM
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
-
noncompetitive inhibition
nitrocatechol sulfate
-
-
nitrocatechol sulfate
-
-
p-hydroxymercuribenzoate
-
-
p-hydroxymercuribenzoate
-
no inhibition at pH 5.5, but at pH 5.0
phophatidylinositol
-
inhibition or activation depends on substrate
phosphate
-
competitive inhibitor
phosphatidylcholine
-
inhibition or activation depends on substrate
PO43-
-
-
PO43-
-
-
psychosine
-
inhibition or activation is substrate-dependent
Semicarbazide
-
-
Sn2+
-
-
SO32-
-
-
SO32-
-
-
SO32-
-
competitive inhibitor
SO42-
-
-
SO42-
-
-
sphingomyelin
-
inhibition or activation depends on substrate
sulfite
-
competitive inhibitor
thiol reagents
-
-
Mn2+
-
MnCl2 reduces the reaction rate in the low millimolar range
additional information
-
the lysosomal degradation of endocytosed enzymes strongly inhibited in CLN6 defective cells
-
additional information
-
estrogens do not significantly change ASA activity in epithelial, HCC1937, or MCF10A cells. Estrone 3-sulfate and estradiol sulfate do not significantly decline ASA in myoepithelial, MCF7, and T47D cells
-
additional information
-
dispersion of cumulus layers of cumulus oocyte complexes still occur in co-incubates with preimmune IgG treated sperm
-
additional information
-
cumulus oocyte complex dispersion caused by AS-A is the same in the presence or absence of apigenin
-
additional information
-
secretion and stability of wtASA is decreased by the coexpression of defective P377L-pdASA
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Bile salts
-
cholate
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
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
-
enzyme cleaves cerebroside sulfates only in the presence of either specific detergent, e.g. taurodeoxycholate or human activator protein
-
Protein factor
-
-
-
Protein factor
-
-
-
Protein factor
-
no requirement for activators when acting on cerebroside sulfate
-
Protein factor
-
activator protein stimulates lipid soluble substrates more than water soluble substrates; degradation of sulfosphingolipids and sulfoglycerolipids with or without activator protein, critical micellar concentration important
-
psychosine
-
inhibition or activation is substrate-dependent
saposin B
-
small activator protein to solubilize hydrophobic substrates
-
sphingomyelin
-
inhibition or activation depends on substrate
taurodeoxycholate
-
-
taurodeoxycholate
-
and MnCl2 or other salt required
taurodeoxycholate
-
acidic form of enzyme is active without taurodeoxycholate
taurodeoxycholate
-
enzyme cleaves cerebroside sulfates only in the presence of either specific detergent, e.g. taurodeoxycholate or human activator protein
ZnCl2
-
-
dolichol
-
at a relative concentration of 30 mol% the lipid stimulates the reaction rate by a factor of 2.7
additional information
Actinia equina, Blaberus fuscus, Helix pomatia, Lima inflata, Lumbricus terrestris
-
low ionic strength, about 0.01 M buffer activity without activator protein or detergent
-
additional information
-
low ionic strength, about 0.01 M buffer activity without activator protein or detergent
-
additional information
-
low ionic strength, about 0.01 M buffer activity without activator protein or detergent
-
additional information
-
low ionic strength, about 0.01 M buffer activity without activator protein or detergent
-
additional information
-
low ionic strength, about 0.01 M buffer activity without activator protein or detergent
-
additional information
-
low ionic strength, about 0.01 M buffer activity without activator protein or detergent
-
additional information
-
phosphatidylinositol and phosphatidylserine have no effect on the rate of sulfatide hydrolysis
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
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
4-nitrocatechol sulfate
-
seminal plasma
1.06
4-nitrocatechol sulfate
-
sperm cell extract
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 - 0.2
cerebroside 3-sulfate
-
-
0.105
cerebroside 3-sulfate
-
-
0.6 - 3.3
cerebroside 3-sulfate
Actinia equina, Blaberus fuscus, Helix pomatia, Lima inflata, Lumbricus terrestris
-
various invertebrates, overview
0.6 - 3.3
cerebroside 3-sulfate
-
-
0.6 - 3.3
cerebroside 3-sulfate
-
various invertebrates, overview
0.06
cerebroside sulfate
-
in presence of 10 mM sodium formate
-
0.06
cerebroside sulfate
-
in presence of 10 mM sodium formate
-
0.07
cerebroside sulfate
-
depends on taurocholate concentrations; in presence of 2 mM taurocholate
-
0.2
cerebroside sulfate
-
-
-
53
Naphthyl sulfate
-
-
0.8
nitrocatechol sulfate
-
-
0.175
p-nitrocatechol sulfate
-
in milt plasma with 60 nM AgNO3
0.26
p-nitrocatechol sulfate
-
-
0.3
p-nitrocatechol sulfate
-
in milt plasma without sodium chloride
0.35
p-nitrocatechol sulfate
-
-
0.45
p-nitrocatechol sulfate
-
in milt plasma with 160 mM sodium chloride
0.81
p-nitrocatechol sulfate
-
in spermatozoon with 160 mM sodium chloride
1
p-nitrocatechol sulfate
-
in spermatozoon without sodium chloride
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
LITERATURE
IMAGE
0.817
4-Methylumbelliferyl sulfate
-
-
16.8
4-nitrocatechol sulfate
-
-
1.45
cerebroside sulfate
-
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
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
-
The enzyme activity is similar in control and beta-carotene treated animals, 7,12-dimethylbenzanthracene administration induces remarkable increase of activity. At addition of beta-carotene to 7,12-dimethylbenzanthracene the enzyme activity shows significant decrease in all the samples examined.
additional information
-
in HEK-293 cells, HeLa cells and COS-7 cells specific activity significantly increased when co-expressed with formylglycine-generating enzyme
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.3
-
narrow pH optimum around pH 4.3
4.5 - 4.8
-
-
4.5
-
-
4.5
-
50 mM sodium formate buffer
4.6 - 5
-
cholate-activated
4.6
-
taurodeoxycholate activated
4.6
-
1-O-alkyl-2-O-acyl-3-O-(beta-D-galactopyranoside-3'-sulfate)-glycerol
4.6
-
cerebroside sulfate
4.7
-
cerebroside 3-sulfate
4.8
-
ascorbate 2-sulfate
4.9
-
in milt plasma
5 - 5.5
-
nitrocatechol 4-sulfate as substrate
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
-
in spermatozoon
5
Q8WNR3
-
5.2
-
4-methylumbelliferyl sulfate
5.3
-
10 mM sodium formate buffer
5.3
-
4-nitrocatechol sulfate
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
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
LITERATURE
37
-
assay
37
-
assay
37
-
assay
37
-
assay
37
-
assay at
37
Q8WNR3
assay at
40
-
milt plasma and spermatozoon
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
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
-
the mean leukocyte enzyme activity in patients with benign breast disease is slightly higher than that (14.3%) that observed in the healthy subjects. In patients with primary breast cancer the enzyme activity is significantly higher than in healthy subjects
Manually annotated by BRENDA team
-
lowest activity of ASA
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
-
the acquisition of enzyme on the sperm surface occurs during epididymal transit
Manually annotated by BRENDA team
-
AS-A is a membrane protein of boar capacitated sperm
Manually annotated by BRENDA team
-
localized on the sperm surface, in the acrosome and postacrosomal regions
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
GeneOntology No.
LITERATURE
SOURCE
-
in the agrosomal region of round and elongating spermatids
-
Manually annotated by BRENDA team
P50428
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
LITERATURE
50000
-
SDS-PAGE
135686
50000
-
enzyme is synthesized as a preprotein with 507 amino acids, the mature protein has 489 amino acids with a calculated mass of 52000; octamer at acidic pH, dimer at neutral pH
135692
50000
-
in the liver samples of control and ethanol treated rats, Western blot analysis
677433
54000
-
in the liver samples of control and ethanol treated rats, Western blot analysis
677433
62000
-
gel filtration, Concanavalia ensiformis agglutinin retained protein
677796
63000
-
copurification with beta-galactosidase, both enzymes aggregate into macromolecular complexes at pH 4 and disaggregate at pH 8, SDS-PAGE
135689
65000
-
gel filtration, wheat germ agglutinin retained protein
677796
66000
-
SDS-PAGE
692081
68000
-
gel filtration, total protein extract of capacitated sperm
677796
100000
-
sedimentation equilibrium ultracentrifugation
135686, 135695
105000
-
-
135681
107000
-
at pH 7.5
135695
123000
-
gradient SDS-PAGE
135511
130000
-
gel filtration
135695
140000
-
zonal and frontal gel filtration
135684
140000
-
-
135695
172000
-
gel-filtration
668313
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 62000, SDS-PAGE
dimer
-
1 * 49000, 1 * 55000, SDS-PAGE
dimer
-
2 * ca. 55000, SDS-PAGE
dimer
-
between pH 5.5-6.5, depends also on ionic strength
dimer
-
at pH 6.5-6.7, the enzyme exists in solution as a dimer
dimer
-
at pH above 6, the enzyme exists in solution as a dimer
dimer
-
2 x 77000, SDS-PAGE
dimer
-
mature enzyme
homodimer
-
at neutral pH
homooctamer
-
at acidic pH
monomer
-
1 * 66000, SDS-PAGE
monomer
-
at pH 5.6 monomer, at pH 4.8 tetramer
octamer
-
tetramer of dimers
octamer
-
ar pH 5.0-5.4, the enzyme exists in solution as a dimer or as an octamer
octamer
-
at pH below 6, the enzyme exists in solution as octamer
oligomer
-
x * 63000, x * 59000, ratio 1.9:1, SDS-PAGE
oligomer
-
early enzyme
tetramer
-
at pH 4.8 tetramer, at pH 5.6 monomer
tetramer
-
aggregation to tetramer at higher concentrations around pH 5, 2 * 49000, 2 * 55000
monomer
-
1 * 140000, each monomer consists of 2 equivalent polypeptide chains
additional information
-
The dimer-octamer equilibrium is regulated by the pH and may be explained by a switch function of Glu424. Glu424 in the conformation suitable for the intramolecular hydrogen bonds to Gln460. Glu424 in the conformation suitable for the intermolecular hydrogen bonds to Phe398
additional information
-
mature lysosomal arylsulfatase A forms dimers at neutral pH, while in the early biosynthetic pathway, arylsulfatase A forms oligomers with more than two subunits. Within a heteromer, the misfolded subunit exerts a dominant negative effect on the wild-type subunit
additional information
P50428
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
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
-
-
glycoprotein
-
-
glycoprotein
-
three N-glycosylation sites are used
glycoprotein
-
A350G mutation results in a loss of a N-glycosylation site
glycoprotein
-
neuraminic acid residues involved in microheterogeneity
glycoprotein
-
high-mannose-type oligosaccharide chains
glycoprotein
-
5-10% carbohydrate content
glycoprotein
-
the wild-type enzyme has three N-glycosylation sites. Only oligosaccharides at the first, Asn158, and the third, Asn350, glycosylation site are phosphorylated, whereas the second, Asn184 is not
glycoprotein
-
three N-glycosylation sites and three N-linked oligosaccharide side chains at asparagine residues 158, 184, and 350, the recombinantly expressed enzyme shows a 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. The composition of the glycans is largely determined by substantial trimming in the medium, the susceptibility for trimming is different for the glycans at the three N-glycosylation sites, which of the glycans is most susceptible to trimming also depends on production conditions. Structure and ligand binding analysis, overview
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
glycoprotein
-
liver: 4.6% carbohydrate
glycoprotein
-
testis: 20% neutral sugar, 0.8% N-acetylneuraminic acid
glycoprotein
-
enzyme possess different number of glycans
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
LITERATURE
10 - 40
Actinia equina, Lima inflata
-
50% loss of activity at 55oC
135675
60
-
t1/2: 7 min
135681
65
-
5 min, no loss of activity
135554
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
Actinia equina, Blaberus fuscus
-
0C, 2 months
-
-20C or 2C, over a week, significant loss of activity
-
-20C, protein: 1 mg/ml
-
-20C, protein: 1 mg/ml, stable for 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
-
-20C or 2C, over a week, significant loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
large scale
-
of the recombinant protein
-
recombinant myc-His- or GFP-tagged ArsA by affinity chromatography from culture cell supernatant
P50428
by gel filtration
-
by gel filtration
-
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
-
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
-
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 patients alleles; transient expression experiments on COS7 cells transfected with enzyme cDNAs carrying the mutations separately and in the combination found in the patient's alleles
-
recombinant expression of myc-His- or GFP-tagged ArsA, the recombinant protein is secreted into the serum-free medium
P50428
expression of wild-type and mutant enzymes in CHO-K1 cells
Q8WNR3
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
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
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
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
N158Q/N350Q
-
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
N350S
-
about 15% reduction of enzyme activity in comparison to wild-type enzyme in vitro
N350S
-
mutation contributes to enzyme activity reduction
N350S
-
about 15% reduction of enzyme activity in comparison to wild-type enzyme in vitro, mutation found in a patient with metachromatic leukodystrophy
P136L
-
inactive misfolded mutant P136LASA
P377L
-
inactive misfolded mutant P377L-pdASA
P425T
-
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
-
mutation contributes to enzyme activity reduction
P426L/N350S/96A>G
-
mutations contribute to sum of the enzyme activity reduction ascribed to each mutation
R288H
-
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
-
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
-
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
-
naturally occuring ARSA polymorphism, causes a severe peripheral neuropathy phenotype
T201C
-
inactive misfolded mutant T201C-ASA
T275M
-
inactive misfolded mutant T275M-ASA
T304M
-
naturally occuring ARSA polymorphism, causes a severe peripheral neuropathy phenotype
C69A
Q8WNR3
site-directed mutagenesis, the mnutant shows abolished enzyme activity and only residual binding to thr sulfoglycolipid substrate
C69A/K123A/K302A
Q8WNR3
site-directed mutagenesis, the mutant shows abolished substrate binding and activity
L52P
-
naturally occuring ARSA polymorphism, causes a severe peripheral neuropathy phenotype
additional information
-
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
-
only substitution of Lys457 causes a reduction of phosphorylation to 33% and increases secretion of the mutant enzyme
additional information
-
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
-
naturally occuring ARSA polymorphisms, overview
additional information
-
secretion and half-life of wild-type enzyme are reduced upon co-expression of defective P377L-pdASA
T391S
-
mutation contributes to enzyme activity reduction
additional information
-
sperm from AS-A null mice show a significant delay in cumulus oocyte complex dispersion, compared with wild-type sperm
additional information
P50428
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
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
arylsulfatase E defiecency in chondrodysplasia punctata
medicine
-
preferred polymorphism in alcohlism, A350G mutation
medicine
-
deficiency in metachromatic leukodystrophy, a sphingolipid storage disorder
medicine
-
assay of activity in leukocytes as a non-invasive diagnostic tool in patients with benign and malignant breast disease
medicine
-
metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of enzyme
medicine
-
the enzyme is implicated in most cases of metachromatic leukodystrophy
medicine
-
therapeutic levels of ARSA overexpression can be safetly achieved. ARSA-transduced cells efficiently repopulate the hematopoietic organs of RAG2-/- gamma-chain-/- mice. ARSA overexpression does not impair clonogenic capacity and multilineage differentiation of human HSPC cells, activation of other sulfatases and is thus unlikely to trigger metabolic imbalances. Moreover, ARSA overexpression does not impair immune functions, behavior and learning abilities
medicine
-
tyrosine sulfation facilitates secretion of ASA, which may have pathophysiological consequences
medicine
-
metachromatic leukodystrophy is caused by deficient activity of arylsulfatase A
medicine
-
enzyme replacement therapy is a therapeutic option for metachromatic leukodystrophy, caused by enzyme-deficiency, and other lysosomal disorders. This therapy depends on N-linked oligosaccharide-mediated delivery of intravenously injected recombinant enzyme to the lysosomes of patient cells
medicine
-
availability of AS-A on the sperm surface is important for the dispersion of cumulus layers of cumulus oocyte complexes
molecular biology
P50428
Ars can be very useful for clarifying the mechanisms underpinning syndromes caused by the deficiency of the function of Ars genes
medicine
-
enzyme effective in dispersing the cumulus cells of rabbit ova
medicine
-
availability of AS-A on the sperm surface is important for the dispersion of cumulus layers of cumulus oocyte complexes