Information on EC 3.1.6.13 - iduronate-2-sulfatase

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The expected taxonomic range for this enzyme is: Euteleostomi

EC NUMBER
COMMENTARY
3.1.6.13
-
RECOMMENDED NAME
GeneOntology No.
iduronate-2-sulfatase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
hydrolysis of the 2-sulfate groups of the L-iduronate 2-sulfate units of dermatan sulfate, heparan sulfate and heparin
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hydrolysis of sulfuric ester
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Glycosaminoglycan degradation
-
Metabolic pathways
-
SYSTEMATIC NAME
IUBMB Comments
L-iduronate-2-sulfate 2-sulfohydrolase
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
2-sulfo-L-iduronate 2-sulfatase
-
-
-
-
chondroitinsulfatase
-
-
-
-
Hunter corrective factor
-
in combination with L-iduronidase
IDS
A0ST40
-
IDS
P22304
-
IDS-Like
-
-
iduronate 2-sulfatase
-
-
iduronate 2-sulfate sulfatase-like
-
-
iduronate sulfatase
-
-
-
-
iduronate sulfatase
A0ST40
-
iduronate sulfatase
-
-
iduronate sulfate sulfatase
-
-
-
-
iduronate-2-sulfatase
-
-
-
-
iduronate-2-sulfatase
-
-
iduronate-2-sulfate sulfatase
-
-
-
-
iduronate-2-sulfate sulfatase
-
-
iduronate-2-sulphatase
-
-
iduronide-2-sulfate sulfatase
-
-
-
-
idurono-2-sulfatase
-
-
-
-
L-iduronate 2-sulfate sulfatase
-
-
-
-
L-idurono sulfate sulfatase
-
-
-
-
sulfatase, L-idurono-
-
-
-
-
sulfo-L-iduronate sulfatase
-
-
-
-
sulfoiduronate sulfohydrolase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
50936-59-9
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
2 forms: A, B
-
-
Manually annotated by BRENDA team
almost total absence of iduronate-2-sulfatase in patients with mucopolysaccharidosis type II compared with control
-
-
Manually annotated by BRENDA team
multiple forms: A, B, C
-
-
Manually annotated by BRENDA team
patients with mucopolysaccharidosis II
-
-
Manually annotated by BRENDA team
patients with mucopolysaccharidosis type II
-
-
Manually annotated by BRENDA team
patients with mucopolysaccharidosis type II, i.e. Hunter disease
-
-
Manually annotated by BRENDA team
Portuguese patients with mucopolysaccharidosis type II
-
-
Manually annotated by BRENDA team
several molecular species
-
-
Manually annotated by BRENDA team
Taiwanese patients with mucopolysaccharidosis type II
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
Italian Hunter syndrome patients show a lack of concordance between IDS genomic DNA and cDNA: presence of wild-type IDS sequence as well as the mutated sequence in cDNA from one or more tissues, but no wild-type IDS sequence is evident in the genomic DNAs derived from these patients, a correction mechanism such as RNA editing may potentially account for this. These Hunter syndrome patients are hemizygous respectively for a nonsense mutation (c.22C>T,p.R8X) and a frameshift micro-insertion (c.10insT,p.P4Sfs) in their genomic DNA. Since both p.R8X mutations are inherited from carrier mothers, somatic mosaicism can be excluded
malfunction
A0ST40, -
downregulation of IDS may be responsible for severe early developmental defects, including a misshapen trunk and abnormal craniofacial cartilages, which is mediated by depauperation of sox10-expressing neural crest cell precursors, which is reverted through the administration of the recombinant enzyme
malfunction
-
Hunter syndrome is caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase. In the absence of sufficient enzyme activity, glycosaminoglycans accumulate in the lysosomes. Complete deletions of the I2S gene (IDS) always result in a severe phenotype, as do complex rearrangements of IDS. Several missense mutations are associated with a severe phenotype (p.R468Q,89-94 p.R468W,95-99 and p.S333L96,100), although each one has in patients with an intermediate or attenuated phenotypes. The mutation c.1122C3T (which creates an alternate splice site with the loss of 20 amino acids) is primarily associated with the attenuated phenotype
malfunction
-
mucopolysaccharidosis, MPS, type II is caused by mutations in the lysosomal enzyme, iduronate-2-sulfatase. MPS-II affects the brain and enzyme replacement therapy is ineffective for the brain, because the enzyme does not cross the blood-brain barrier
physiological function
-
recombinant IDS-Like activity increases when passed from culture M6 (11.34 g/l of glycerol) to M7 (25.53 g/l of glycerol), from 14.7 to 29.5 nmol/h/mg of total protein, between the 33 and 47 h of culture. In M8 (40.13 g/l of glycerol), the recombinant IDS-Like activity is 7.3 nmol/h/mg of total protein at 47h of culture. In M9 (83.32 g/l of glycerol), no recombinant IDS-Like activity is detected. Recombinant IDS-Like activity is lower when extra-cellular proteolytic activity increases
physiological function
-
in AAV2/5CMV-hIDS-injected mucopolysaccharidosis type II mice with Hunter syndrome, rescue of brain defects. The central nervous system correction arises from the crossing of the blood-brain barrier by the IDS enzyme
physiological function
-
overexpression of IDS enhances glucose-induced insulin secretion in INS1E cells by activation of the exocytotic process. IDS overexpression is associated with a gain of function detected by a reduction in heparan sulfate content. IDS potentiates the glucose-stimulated insulin secretory response compared with controls (61%) with no changes in insulin mRNA levels or insulin peptide content. Increase in the number of granules in the immediate vicinity of the plasma membrane in IDS-transfected cells and a decrease in total vesicles per square micrometer. IDS overexpression induces phosphorylation of protein kinase C alpha and its newly myristoylated alanine-rich C kinase substrate, MARCKS
physiological function
-
HIRMAb-IDS fusion protein crosses the blood-brain barrier on the endogenous insulin receptor and acts as a molecular Trojan horse to ferry the IDS into brain. The fusion protein is taken up by Hunter fibroblasts, and the accumulation of glycosoaminoglycans in fibroblasts null for the sulfatase is decreased 84% by treatment with the fusion protein. The fusion protein heavy chain reacts with antibodies to both human IgG and human IDS. The fusion protein is a bifunctional molecule and binds both the HIR extracellular domain with comparable affinity to the chimeric HIRMAb and has high IDS enzyme activity
physiological function
-
a deficiency of iduronate-2-sulfatase causes mucopolysaccharidosis type II (Hunter syndrome), which is a progressive, multisystemic disease: patients with the severe form of the disease have cognitive impairment and typically die in the second decade of life, whereas patients with the less severe form do not experience significant cognitive involvement and may survive until the fifth or sixth decade of life
physiological function
-
mucopolysaccharidosis type II carriers show lower plasma and leukocyte IDS activities but this reduction is generally associated neither with age, changes in levels of urinary glycosaminoglycans nor with the occurrence of clinical manifestations
physiological function
A0ST40, -
iduronate sulfatase plays a critical role during early vertebrate developments
physiological function
-
a 6-year-old male suffering from a severe type of Hunter disease (deficiency of IDS) with cord blood stem cell transplantation died at 10 months post-therapy due to a laryngeal post-transplantation lymphoproliferative disorder
physiological function
-
male patients, ages 21-53 years, receiving weekly intravenous infusions of 0.5 mg/kg idursulfase for 12 months, show significant reductions in lysosomal storage and several clinical improvements. Idursulfase is generally well-tolerated. Infusion-related reactions occur in 50% of patients and are mostly mild with transient skin reactions that do not require medical intervention. Two infusion-related reactions are assessed as serious (urticaria and vasovagal syncope)
malfunction
-
iduronate-2-sulfate sulfatase, IDS, deficiency causes the Hunter syndrome ormucopolysaccharidosis type II
additional information
-
development of an expression system for human recombinant IDS in Pichia pastoris and of a detection method for enzyme detection during production and purification processes, which can be used also to measure the enzyme in human fluids, immunoquantification assay using rabbit IgG and chicken IgY, overview
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
4-methylumbelliferyl-2-iduronate-2-sulfate + H2O
4-methylumbelliferol + iduronate-2-sulfate
show the reaction diagram
-
artificial substrate
-
-
?
4-methylumbelliferyl-alpha-iduronide 2-sulfate + H2O
4-methylumbelliferyl-alpha-iduronide + sulfate
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl-alpha-iduronide-2-sulfate + H2O
4-methylumbelliferyl-alpha-iduronide + sulfate
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl-alpha-iduronide-2-sulfate + H2O
4-methylumbelliferyl-alpha-iduronide + sulfate
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl-alpha-iduronide-2-sulfate + H2O
4-methylumbelliferyl-alpha-iduronide + sulfate
show the reaction diagram
A0ST40, -
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide-2-sulfate + H2O
4-methylumbelliferyl-alpha-L-iduronide + sulfate
show the reaction diagram
-
-
-
-
?
dermatan sulfate + H2O
dermatan + sulfate
show the reaction diagram
-
-
-
-
?
dermatan sulfate + H2O
dermatan + sulfate
show the reaction diagram
-
-
-
-
?
dermatan sulfate + H2O
dermatan + sulfate
show the reaction diagram
-
-
-
-
?
dermatan sulfate + H2O
dermatan + sulfate
show the reaction diagram
-
-
-
-
?
heparan sulfate + H2O
dermatan + sulfate
show the reaction diagram
-
-
-
-
?
heparan sulfate + H2O
dermatan + sulfate
show the reaction diagram
-
-
-
-
?
heparan sulfate + H2O
dermatan + sulfate
show the reaction diagram
-
-
-
-
?
heparan sulfate + H2O
dermatan + sulfate
show the reaction diagram
-
-
-
-
?
heparin + H2O
desulfated heparin + sulfate
show the reaction diagram
-
-
-
-
?
O-(alpha-L-idopyranosyluronic acid 2-sulfate)-(1-4)-2,5-anhydro-D-mannitol + H2O
O-(alpha-L-idopyranosyluronic acid)-(1-4)-2,5-anhydro-D-mannitol + sulfate
show the reaction diagram
-
-
-
-
?
O-(alpha-L-idopyranosyluronic acid 2-sulfate)-(1-4)-2,5-anhydro-D-mannitol 6-sulfate + H2O
O-(alpha-L-idopyranosyluronic acid)-(1-4)-2,5-anhydro-D-mannitol 6-sulfate + sulfate
show the reaction diagram
-
-
-
-
?
O-(alpha-L-idopyranosyluronic acid-2-sulfate)-(1-4)-2,5 anhydromannose-6-sulfate
?
show the reaction diagram
-
-
-
?
O-(alpha-L-iduronic acid 2-sulfate)-(1-3)-2,5-anhydro-D-talitol 4-sulfate + H2O
O-(alpha-L-iduronic acid)-(1-3)-2,5-anhydro-D-talitol 4-sulfate + sulfate
show the reaction diagram
-
-
-
-
?
O-(alpha-L-iduronic acid 2-sulfate)-(1-4)-D-O-(alpha 2-sulfaminoglucosamine 6-sulfate)-(1-4)-L-O-(alpha-L-iduronic acid 2-sulfate)-D-O-2,5-anhydro-mannitol 6-sulfate + H2O
O-(alpha-L-iduronic acid)-(1-4)-D-O-(alpha 2-sulfaminoglucosamine 6-sulfate)-(1-4)-L-O-(alpha-L-iduronic acid)-D-O-2,5-anhydro-mannitol 6-sulfate + sulfate
show the reaction diagram
-
-
-
-
?
O-(alpha-L-iduronic acid 2-sulfate)-(1-4)-D-O-(alpha 2-sulfaminoglucosamine 6-sulfate)-(1-4)-O-(beta-D-glucuronic acid or L-iduronic acid)-(1-4)-D-O-(alpha-N-acetylglucosamine)-(1-3)-D-O-gulonic acid + H2O
O-(alpha-L-iduronic acid)-(1-4)-D-O-(alpha 2-sulfaminoglucosamine 6-sulfate)-(1-4)-O-(beta-D-glucuronic acid or L-iduronic acid)-(1-4)-D-O-(alpha-N-acetylglucosamine)-(1-3)-D-O-gulonic acid + sulfate
show the reaction diagram
-
-
-
-
?
O-(alpha-L-iduronic acid 2-sulfate)-(1-4)-D-O-(alpha glucosamine 6-sulfate)-(1-4)-L-O-(alpha-L-iduronic acid 2-sulfate)-D-O-2,5-anhydro-mannitol 6-sulfate + H2O
O-(alpha-L-iduronic acid)-(1-4)-D-O-(alpha glucosamine 6-sulfate)-(1-4)-L-O-(alpha-L-iduronic acid)-D-O-2,5-anhydro-mannitol 6-sulfate + sulfate
show the reaction diagram
-
-
-
-
?
O-(alpha-L-iduronic acid 2-sulfate)-(1-4)-D-O-(alpha-N-acetylglucosamine 6-sulfate)-(1-4)-L-O-(alpha-L-iduronic acid 2-sulfate)-D-O-2,5-anhydro-mannitol 6-sulfate + H2O
O-(alpha-L-iduronic acid)-(1-4)-D-O (alpha N-acetylglucosamine 6-sulfate)-(1-4)-L-O-(alpha-L-iduronic acid)-D-O-2,5-anhydro-mannitol 6-sulfate + sulfate
show the reaction diagram
-
-
-
-
?
heparin + H2O
desulfated heparin + sulfate
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
The enzyme has a potential role in normal pathway of lysosomal degradation of secretory peptides and is likely to be essential to maintain pancreatic beta-cell function
-
?
additional information
?
-
-
the enzyme is involved in the catabolism of the mucopolysaccharides heparan and dermatan sulfate
-
?
additional information
?
-
-
the enzyme is involved in the sequential degradation of the glycosaminoglycans heparan sulfate and dermatan sulfate
-
?
additional information
?
-
-
the enzyme is responsible for heparin sulfate and dermatan sulfate degradation
-
?
additional information
?
-
-
the enzyme is responsible for heparin sulfate and dermatan sulfate degradation
-
?
additional information
?
-
P22304
involved in the degradation of the glycosaminoglycans heparan sulfate and dermatan sulfate. An enzyme deficiency causes the lysosomal storage disorder muco-polysaccharidosis type II
-
-
-
additional information
?
-
-
mucopolysaccharidosis type II is a lysosomal storage disorder related to a deficiency in the enzyme iduronate-2-sulfatase
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
dermatan sulfate + H2O
dermatan + sulfate
show the reaction diagram
-
-
-
-
?
dermatan sulfate + H2O
dermatan + sulfate
show the reaction diagram
-
-
-
-
?
heparan sulfate + H2O
dermatan + sulfate
show the reaction diagram
-
-
-
-
?
heparan sulfate + H2O
dermatan + sulfate
show the reaction diagram
-
-
-
-
?
heparin + H2O
desulfated heparin + sulfate
show the reaction diagram
-
-
-
-
?
heparin + H2O
desulfated heparin + sulfate
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
The enzyme has a potential role in normal pathway of lysosomal degradation of secretory peptides and is likely to be essential to maintain pancreatic beta-cell function
-
?
additional information
?
-
-
the enzyme is involved in the catabolism of the mucopolysaccharides heparan and dermatan sulfate
-
?
additional information
?
-
-
the enzyme is involved in the sequential degradation of the glycosaminoglycans heparan sulfate and dermatan sulfate
-
?
additional information
?
-
-
the enzyme is responsible for heparin sulfate and dermatan sulfate degradation
-
?
additional information
?
-
-
the enzyme is responsible for heparin sulfate and dermatan sulfate degradation
-
?
additional information
?
-
P22304
involved in the degradation of the glycosaminoglycans heparan sulfate and dermatan sulfate. An enzyme deficiency causes the lysosomal storage disorder muco-polysaccharidosis type II
-
-
-
additional information
?
-
-
mucopolysaccharidosis type II is a lysosomal storage disorder related to a deficiency in the enzyme iduronate-2-sulfatase
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Mn2+
-
stimulates at 2 mM
additional information
-
effect of IDS on insulin secretion does not result from increased intracellular Ca2+ signaling
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
chondroitin 4-sulfate
-
at 0.1 mM
chondroitin 6-sulfate
-
at 0.1 mM
Cl-
-
at high concentration
Heparan sulfate
-
-
N-actetylglucosamine 6-sulfate-(1-4)-2,5-anhydro-D-mannitol 6-sulfate
-
competitive inhibitor
-
NaCl
-
inhibits at 10-100 mM
NaCl
-
due to Cl-
nitrocatechol sulfate
-
competitive inhibitor
O-(alpha-L-idopyranosyluronic acid 2-sulfate)-(1-4)-2,5-anhydro-D-mannitol
-
competitive inhibitor
O-(alpha-L-idopyranosyluronic acid 2-sulfate)-(1-4)-2,5-anhydro-D-mannitol 6-sulfate
-
competitive inhibitor
O-(alpha-L-idopyranosyluronic acid)-(1-4)-2,5-anhydro-D-mannitol 6-sulfate
-
competitive inhibitor
Phenolphthalein disulfate
-
-
SO42-
-
organic sulfates
suramin
-
in vivo and in vitro
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
additional information
-
When islets are cultured in different concentrations of D-glucose, the levels of enzyme mRNA increases, in a dose-dependent manner. Mannoheptulose completely blocks the effect of glucose.
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0192
-
O-(alpha-L-idopyranosyluronic acid 2-sulfate)-(1-4)-2,5-anhydro-D-mannitol
-
-
0.0025
0.01
O-(alpha-L-idopyranosyluronic acid 2-sulfate)-(1-4)-2,5-anhydro-D-mannitol 6-sulfate
-
pH dependent
0.003
-
O-(alpha-L-idopyranosyluronic acid 2-sulfate)-(1-4)-2,5-anhydro-D-mannitol 6-sulfate
-
recombinant protein
0.0115
-
O-(alpha-L-idopyranosyluronic acid 2-sulfate)-(1-4)-2,5-anhydro-D-mannitol 6-sulfate
-
pool 1 from urine
0.012
-
O-(alpha-L-idopyranosyluronic acid 2-sulfate)-(1-4)-2,5-anhydro-D-mannitol 6-sulfate
-
in presence of 7 mM NaCl
0.013
-
O-(alpha-L-idopyranosyluronic acid 2-sulfate)-(1-4)-2,5-anhydro-D-mannitol 6-sulfate
-
form A
0.013
-
O-(alpha-L-idopyranosyluronic acid 2-sulfate)-(1-4)-2,5-anhydro-D-mannitol 6-sulfate
-
pool 2 in urine
0.015
-
O-(alpha-L-idopyranosyluronic acid 2-sulfate)-(1-4)-2,5-anhydro-D-mannitol 6-sulfate
-
form B
0.043
-
O-(alpha-L-idopyranosyluronic acid 2-sulfate)-(1-4)-2,5-anhydro-D-mannitol 6-sulfate
-
in presence of 70 mM NaCl
0.133
-
O-(alpha-L-idopyranosyluronic acid-2-sulfate)-(1-4)-2,5 anhydromannose-6-sulfate
-
mutant R88H
0.327
-
O-(alpha-L-idopyranosyluronic acid-2-sulfate)-(1-4)-2,5 anhydromannose-6-sulfate
-
wild-type enzyme
0.0007
0.0011
O-(alpha-L-iduronic acid 2-sulfate)-(1-3)-2,5-anhydro-D-talitol 4-sulfate
-
pH dependent
0.0014
-
O-(alpha-L-iduronic acid 2-sulfate)-(1-4)-D-O-(alpha 2-sulfaminoglucosamine 6-sulfate)-(1-4)-L-O-(alpha-L-iduronic acid 2-sulfate)-D-O-2,5-anhydro-mannitol 6-sulfate
-
pH dependent
0.0019
-
O-(alpha-L-iduronic acid 2-sulfate)-(1-4)-D-O-(alpha 2-sulfaminoglucosamine 6-sulfate)-(1-4)-O-(beta-D-glucuronic acid or L-iduronic acid)-(1-4)-D-O-(alpha-N-acetylglucosamine)-(1-3)-D-O-gulonic acid
-
pH dependent
0.0025
-
O-(alpha-L-iduronic acid 2-sulfate)-(1-4)-D-O-(alpha glucosamine 6-sulfate)-(1-4)-L-O-(alpha-L-iduronic acid 2-sulfate)-D-O-2,5-anhydro-mannitol 6-sulfate
-
pH dependent
0.0031
-
O-(alpha-L-iduronic acid 2-sulfate)-(1-4)-D-O-(alpha-N-acetylglucosamine 6-sulfate)-(1-4)-L-O-(alpha-L-iduronic acid 2-sulfate)-D-O-2,5-anhydro-mannitol 6-sulfate
-
pH dependent
0.01
0.02
sulfoiduronyl sulfoanhydromannitol
-
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.000006
0.00066
-
hrIDS detection by ELISA-sandwich and fluorometric assay in Pichia pastoris culture samples, substrate is 4-methylumbelliferyl-2-iduronate-2-sulfate, pH not specified in the publication, temperature not specified in the publication, overview
0.00063
0.0021
-
enzyme determination in human plasma samples by a Fluorometric method, and ELISA double sandwich technique after several freeze and thawing cycles, substrate is 4-methylumbelliferyl-2-iduronate-2-sulfate, pH not specified in the publication, temperature not specified in the publication, overview
0.00083
-
-
-
0.006
-
-
untreated neuronal cells, comparison to cells after adenoviral infection
0.00725
-
-
untreated control cells, comparison to cells after adenoviral infection
11.9
-
-
-
20.8
-
-
recombinant protein
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
3.9
5.7
-
depending on substrate
3.9
5.7
-
-
4
-
-
precipitous decrease in activity at higher pH
4.1
5.3
-
form C, depending on ionic strength
4.4
5.3
-
form B, depending on ionic strength
4.5
5.3
-
form A, depending on ionic strength
4.5
5.3
-
recombinant protein
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
assay at
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.03
-
-
heavy-chain HIRMAb-IDS fusion protein, calculated from sequence
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
patients with mucopolysaccharidosis type II
Manually annotated by BRENDA team
A0ST40, -
adult
Manually annotated by BRENDA team
-
IDS is present in many cells of the mucopolysaccharidosis type II post-cord blood stem cell transplantation patient as well as in the non-mucopolysaccharidosis type II control. Many IDS-immunoreactive large cells are found in the non-mucopolysaccharidosis type II control, whereas only a few IDS-immunoreactive small cells are found in the mucopolysaccharidosis type II post-cord blood stem cell transplantation patient. Most IDS-positive small cells are localized in perivascular spaces in the mucopolysaccharidosis type II post-cord blood stem cell transplantation patient. Many of them are in the distended Virchow-Robin spaces, and some of them in the brain parenchyma. No IDS-immunoreactive neurons in the mucopolysaccharidosis type II post-cord blood stem cell transplantation patient. IDS is present exclusively in CD68-positive microglia/monocytes in the brain of Hunter disease patient, whereas that in the normal brain is also detected in neurons and oligodendrocytes
Manually annotated by BRENDA team
A0ST40, -
IDS activity already detected at the 64-cell stage, and increases at 6.5 hours post fertilization, during the onset of gastrulation. A gradual decrease of enzymatic activity from 24 hours post fertilization to 5 dpf
Manually annotated by BRENDA team
-
primary epithelial cell, highest activity of galacose 6-sulfatase and aryl sulfatase B of all the cell lines tested
Manually annotated by BRENDA team
A0ST40, -
embryo and adult
Manually annotated by BRENDA team
A0ST40, -
embryo
Manually annotated by BRENDA team
A0ST40, -
adult
Manually annotated by BRENDA team
-
IDS enzyme activity in mucopolysaccharidosis type II patient at 10 months post-cord blood stem cell transplantation
Manually annotated by BRENDA team
A0ST40, -
embryo
Manually annotated by BRENDA team
-
contains only form A
Manually annotated by BRENDA team
-
IDS enzyme activity in mucopolysaccharidosis type II patient at 10 months post-cord blood stem cell transplantation
Manually annotated by BRENDA team
A0ST40, -
embryo
Manually annotated by BRENDA team
-
IDS enzyme activity in mucopolysaccharidosis type II patient at 10 months post-cord blood stem cell transplantation reaches about 40% of the normal control level
Manually annotated by BRENDA team
-
remarkably low activity of arylsulfatase A, arylsulfatase B, galacose 6-sulfatase and steryl sulfatase, but not iduronate 2-sulfatase
Manually annotated by BRENDA team
A0ST40, -
vascular mesenchyme of the embryo
Manually annotated by BRENDA team
A0ST40, -
adult
Manually annotated by BRENDA team
-
primary myoepithelial cell, highest activity of steryl sulfatase and aryl sulfatase B of all the cell lines tested
Manually annotated by BRENDA team
A0ST40, -
adult
Manually annotated by BRENDA team
A0ST40, -
embryo
Manually annotated by BRENDA team
-
contains only form C; distribution of the forms A, B and C in body fluids
Manually annotated by BRENDA team
-
cultured fibroblasts
Manually annotated by BRENDA team
-
remarkably low activity of arylsulfatase A, arylsulfatase B, galacose 6-sulfatase and steryl sulfatase, but not iduronate 2-sulfatase
Manually annotated by BRENDA team
A0ST40, -
embryo
Manually annotated by BRENDA team
additional information
A0ST40, -
embryonic otic vesicle, splanchnocranium and pectoral fin bud
Manually annotated by BRENDA team
additional information
-
in cerebrum, very low IDS enzyme activity in mucopolysaccharidosis type II patient at 10 months post-cord blood stem cell transplantation, IDS enzyme activity reaches only 1% of the normal control level
Manually annotated by BRENDA team
additional information
-
development of an ELISA system to detect and quantify IDS with IgY antibodies, overview
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
42000
45000
-
SDS-PAGE
42000
65000
-
gel filtration
45000
-
-
Western blot analysis
55000
-
-
mature form after deglycosylation, recombinant protein, SDS-PAGE
60000
-
-
after endoglucosidase treatment, SDS-PAGE
76000
-
-
recombinant IDS, immunoblot analysis
80000
100000
-
sucrose density gradient centrifugation
80000
115000
-
form A, gel filtration, SDS-PAGE
81000
83000
-
form B, gel filtration
83000
94000
-
form A, sucrose density gradient centrifugation
90000
-
-
recombinant protein,SDS-PAGE
95000
-
-
form A, B, gel filtration
95000
-
-
-
108000
-
-
heavy-chain HIRMAb-IDS fusion protein, calculated from sequence
132000
-
-
form C, gel filtration
135000
-
-
heavy-chain HIRMAb-IDS fusion protein, Western blotting
170000
190000
-
form B, sucrose density gradient centrifugation
additional information
-
-
the fusion protein is about 80 kDa larger than the heavy chain of the chimeric HIRMAb
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
COS 7 cells transfected with wild-type enzyme expression vector, produce three polypeptides of 90000, 62000 and 45000 Da, corresponding to precursor, intermediate and mature forms of enzyme, pulse-chase labelling
?
-
x * 55000, Western blot analysis, wild-type enzyme
?
-
x * 42000-45000, SDS-PAGE
?
-
x * 78000, precursor form, x * 46000-48000 and x * 55000, mature forms, SDS-PAGE
dimer
-
1 * 42000 + 1 * 18000, SDS-PAGE, reduced
heterotetramer
-
HIRMAb-IDS fusion protein
monomer
-
1 * 80000-90000, sucrose density gradient centrifugation, SDS-PAGE, after treatment with mercaptoethanol
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
glycoprotein
-
contains sialic acid residues
glycoprotein
-
eight glycosylation sites
glycoprotein
-
-
proteolytic modification
-
proteolytic maturation of 78000 Da precursor form to 46000-48000 and 55000 Da mature forms
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
3.6
-
-
less stable
7
-
-
stable at neutral pH
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
50
-
-
stable for 5 min
50
-
-
pH 4.0, 0.1 M sodium acetate, 1% bovine serum albumin, 2 h, 50% inactivation
50
-
-
stable for 10 min
55
-
-
30 min, 50% loss of activity of form A, 45 min, 50% loss of activity of form B
64
-
-
5 min, 50% loss of activity
75
-
-
2 min, complete loss of activity
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
bovine serum albumin stabilizes
-
in water rapid loss of activity
-
The half-life of intracellular enzyme taken up by peripheral blood lymphocytes from patients with Hunter syndrome from the medium are determined to be 1.9 days.
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20°C, neutral pH, for one year or more
-
4°C, pH 7.2, 150 mM NaCl, several days
-
frozen
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
HIRMAb-IDS fusion protein purified by protein A affinity chromatography, to homogeneity
-
of the recombinant protein
-
to homogeneity
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
chimeric IDS-GFP cloned in a pCS2 vector under the control of the cytomegalovirus promoter. The resulting construct transfected into FU20 primary fibroblasts
A0ST40, -
AAV type 2/5 vector carrying human IDS cDNA under the control of the cytomegalovirus promoter (AAV2/5CMV-hIDS) administered in day 2 idsy/- mouse pups
-
development of an expression system for human recombinant IDS in Pichia pastoris and of a detection method for enzyme detection during production and purification processes, which can be used also to measure the enzyme in human fluids, immunoquantification assay using rabbit IgG and chicken IgY, overview
-
expressed in COS-7 cells
-
expression in CHO cell
-
expression in CHO cells
-
expression in COS 7 cells
-
expression in COS cells and lymphoblastoid cells
-
expression of identified mutations in COS 7 cells
-
full-length IDS cDNA amplified and cloned into the pCR2.1-TOPO vector
-
hIDS c-myc subcloned into pcDNA 3.1/Hygro(-). INS1E cells transiently transfected with the IDS construct
-
HIRMAb-IDS fusion protein (IDS cDNA, encoding Ser26-Pro550, minus the 25 amino acid signal peptide, fused to the carboxyl terminus of the heavy chain of a chimeric monoclonal antibody to the human insulin receptor) expressed in COS cells
-
Pichia pastoris strain GS115:His- transformed with the integrative plasmid pPIC9-hIDS-Like (Clone IDS28)
-
production of the recombinant enzyme by a transfected human clone: Bosc 23 cells and production of the recombinant enzyme by adenoviral transduction of neuronal cells: SK-N-BE
-
the expression of enzyme from three promoters in four retroviral vectors are studied
-
the recombinant fusion enzyme protein is triaged to the lysosomal compartment of MPS-II fibroblasts, expression in CHO cells as IgG-sulfatase fusion protein with the enzyme fused to a genetically engineered monoclonal antibody against the human insulin receptor, i.e. HIRMAb. The cDNA encoding the human IDS cDNA, minus the sequence encoding the signal peptide, is fused to the carboxyl terminus of the CH3 region of the heavy chain of the chimeric HIRMAb
-
expressed in islets, alpha and beta clonal cells
-
production of the recombinant enzyme by adenoviral transduction of glial cells: C6
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
knocking down with antisense morpholino oligos, significant decrease in the enzymatic activity after 24 hours post-morpholino injection in morphants (72.3% of the control). Inability of the morpholino to completely suppress the IDS activity due to maternally derived enzyme. Increased transforming growth factor beta signalling is tightly associated with downregulation of iduronate sulfatase function
A0ST40, -
IDS is abundantly expressed during early developmental stages, IDS mRNAs is present already at the two-cell stage, pointing to a maternal origin of the transcripts. At later stages, ubiquitous expression from shield to 24 hours post fertilization. At 24 hours post fertilization a visible increased concentration of transcripts detectable in the head, particularly in the region surrounding the midbrain-hindbrain boundary. From the hatching phase (48 hours post fertilization), restriction of IDS transcription to the head, with a more intense staining in the retina, otic vesicles, the tectum and the vascular mesenchyme. More caudally, expression in the liver and pectoral fin buds. At 72 hours post fertilization IDS transcripts mainly present in two distinct areas, corresponding to the splanchnocranium and the gut, and a faint staining still in the otic vesicle. This expression pattern becomes more defined at 120 hours post fertilization, when the intensity of the hybridization signal in the gut and splanchnocranium. In the adult stage, IDS mRNAs in all the examined tissues
A0ST40, -
no IDS expression in the brain samples of the control (wild-type and idsy/-) or treated (after 1 month or 18 months of AAV2/5CMV-hIDS therapy) mice
-
although IDS transcript levels are reduced (51-71% normal) in Hunter syndrome patients, some wild-type IDS protein is detectable
-
presence of wild-type IDS mRNA-transcripts in Hunter syndrome patients, but no wild-type IDS genomic sequence detectable
-
IDS-Like expression is induced by methanol addition
-
IDS expression in the liver and lungs of the control (wild-type and idsy/-) or treated (after 1 month or 18 months of AAV2/5CMV-hIDS therapy) mice
-
IDS expression restrictedly observed in human pancreatic islet
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
A85T
-
mutation identified in patient with mucopolysaccharidosis type II, attenuated phenotype. 1.2% residual activity, presence of both the precursor form and processed form of enzyme
C84A
-
loss of activity in mutant
C84S
-
artificial mutation in predicted active site. No enzymic acitivity, presence of both the precursor form and processed form of enzyme
C84T
-
loss of activity in mutant
C84T
-
artificial mutation in predicted active site. No enzymic acitivity, presence of both the precursor form and processed form of enzyme
D148N
-
mutation identified in patient with mucopolysaccharidosis II
D148V
-
the mutation perturbs the structure or molecular interactions of the enzyme, leading to loss of enzyme activity and severe phenotype of disease
D269V
-
mutation identified in patient with mucopolysaccharidosis II
D69V
-
mutation identified in patient with mucopolysaccharidosis II
E254X
-
the mutation produces truncated protein lacking 54% of the IDS protein, which leads to severe clinical presentations
G140R
-
the mutant has 22% of the activity from cells expressing wild type IDS
G224A
-
inactive mutant, causing severe phenotype of disease
K227E
-
the mutation perturbs the structure or molecular interactions of the enzyme, leading to loss of enzyme activity and severe phenotype of disease
L339P
-
L339P is a mucopolysaccharidosis type II-causing mutation affecting maturation of the protein, the missense variant has stable mRNA but the residual enzyme activity remains 1.2% of wild type level
P86L
-
mutation identified in patient with mucopolysaccharidosis II
P86L
-
mutation identified in patient with mucopolysaccharidosis type II, severe phenotype. No residual activity, presence of precursor form of enzyme
P86L
-
the mutation activates multiple cryptic splice sites, resulting in aberrantly spliced transcripts of IDS
Q389X
-
the nonsense mutation leads to premature chain termination at codom 398 and causes mucopolysaccharidosis type II
Q531X
-
mutation identified in patient with mucopolysaccharidosis type II, attenuated phenotype. 2.4% residual activity, presence of a truncated 68000 Da protein form
R101C
-
the mutant shows 97% of the wild type activity
R443X
-
the mutation produces truncated protein lacking 20% of the IDS protein, which leads to severe clinical presentations
R468L
-
mutation identified in patient with mucopolysaccharidosis type II, severe phenotype. No residual activity, presence of precursor form of enzyme
R468Q
-
mutations identified in Taiwanese patients with mucopolysaccharidosis type I, mutations R468Q and R468W together account for 48% of mutations found
R468Q
-
mutation identified in patient with mucopolysaccharidosis type II, severe phenotype. No residual activity, presence of precursor form of enzyme
R468Q
-
the mutant shows 1.4% of the wild type activity
R468W
-
mutations identified in Taiwanese patients with mucopolysaccharidosis type I, mutations R468Q and R468W together account for 48% of mutations found
R48P
-
mutation identified in patient with mucopolysaccharidosis type II, attenuated phenotype. 0.33% residual activity, presence of both the precursor form and processed form of enzyme
R88C
-
mutation identified in patient with mucopolysaccharidosis II
R88H
-
13.7% residual enzyme activity in comparison to wild-type enzyme
R88P
-
total absence of residual activity
S333L
-
mutation identified in patient with mucopolysaccharidosis type II, severe phenotype. No residual activity, presence of precursor form of enzyme
S349I
-
mutation identified in patient with mucopolysaccharidosis type II, severe phenotype. No residual activity, presence of precursor form of enzyme
S369X
-
the nonsense mutation leads to premature chain termination at codom 369 and causes mucopolysaccharidosis type II
W337R
-
mutation identified in patient with mucopolysaccharidosis type II, attenuated phenotype. 0.2% residual activity, presence of both the precursor form and processed form of enzyme
L339R
-
the missense variant has stable mRNA but the residual enzyme activity remains 2.3% of wild type level
additional information
-
R88H, R88P, T118I, 959delT, R468Q mutations are identified in Hunter syndrome patients
additional information
-
K347T, N265I, 473delTCC, 533delTT mutations are identified in four out of 28 Hunter syndrome patients
additional information
-
in 25 Hunter syndrome patients 20 mutations of the gene are identified of which 13 mutations are novel
additional information
-
Q80X, R88C, c145-161del insT, D198G, c247delG, L259P, S333L, E341K, W345X, R468Q, P480R, R48P mutations are identified in Hunter syndrome patients
additional information
-
identification of 10 different mutations in Taiwanese patients with mucopolysaccharidosis type I, mutations R468Q and R468W together accounting for 48% of mutations found
additional information
-
analysis of mutations identified in patients with mucopolysaccharidosis type II. Mutations lead to aberrant precursor forms and loss of normal maturation of precursor. Mutant enzymes exhibit 2-4% of wild-type activity
additional information
-
analysis of enzyme gene in Portuguese patients with mucopolysaccharidosis type II. Splice mutations at the IDS locus account for almost 56% of cases. Mutations include six intronic splice mutations, c.104?2A>G, c.241?2A>G, c.241?1G>A, c.418+1G>A, c.880?8A>G and c.1181?1G>C, two exonic splice mutations, c.1006G>C and c.1122C>T, five missense mutations, D269V, D69V, D148N, R88C and P86L, one nonsense mutation, Q465Ter, one total IDS gene deletion, and one rearrangement involving a IDS gene inversion
additional information
-
characterization of three mucopolysaccharidosis II patients with multiple aberrant transcripts due to three different point mutations. Mutations lead to production of only abnormally spliced transcripts (c.418+1G>C) or to abnormally spliced transcripts in addition to correctly spliced transcripts bearing the respective missence mutation (c.419G>T, and c.245C>T)
additional information
-
to deliver the enzyme across the human blood-brain barrier, the sulfatase is re-engineered as an IgG-sulfatase fusion protein with a genetically engineered monoclonal antibody against the human insulin receptor. The human insulin receptor monoclonal antibody HIRMAb part of the HIRMAb-IDS fusion protein acts as a molecular Trojan horse to ferry the fused IDS across the blood-brain barrier, overview. The HIRMAb-IDS fusion protein is tritiated and injected intravenously into the adult Rhesus monkey at a low dose of 0.1 mg/kg. The IDS enzyme activity in plasma is elevated 10fold above the endogenous level, and therapeutic plasma concentrations are generated in vivo. The uptake of the HIRMAb-IDS fusion protein in the brain is sufficiently high to produce therapeutic concentrations of IDS in the brain following IV administration of the fusion protein
W337X
-
the mutation produces truncated protein lacking 39% of the IDS protein, which leads to severe clinical presentations
additional information
-
in 25 Hunter syndrome patients 20 mutations of the gene are identified of which 13 mutations are novel
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
A0ST40, -
use of zebrafish as a novel tool to better understand lysosomal storage disorder pathogenesis
diagnostics
-
sulfatases are potential therapeutic biopharmaceuticals
drug development
-
HIRMAb-IDS fusion protein is a bifunctional IgG-sulfatase fusion protein, specifically engineered for targeted drug delivery across the human blood-brain barrier
medicine
-
endocytosis of the recombinant enzyme by human fibroblasts
medicine
-
deficiency in Hunters syndrome, mucopolysaccharidosis II
medicine
-
in humans, the inherited deficiency of the enzyme activity results in mucopolysaccharidosis type II, the Hunter syndrome
medicine
-
the inherited deficiency results in mucopolysaccharidosis type II, the Hunter syndrome, studies of transfer of the recombinant enzyme into brain cells in vitro
medicine
-
the inherited deficiency results in mucopolysaccharidosis type II, the Hunter syndrome
medicine
-
the inherited deficiency results in mucopolysaccharidosis type II
medicine
-
monoclonal antibodies demonstrate the capacity to differentiate progressive structural changes in iduronate-2-sulphatase and can be used to characterize the severity of mucopolysaccharidosis type II in patients based on variable denatured microstates
medicine
-
identification of 10 different mutations in Taiwanese patients with mucopolysaccharidosis type I, mutations R468Q and R468W together accounting for 48% of mutations found. Due to overlapping significant wide range of enzyme activity in normal controls and in carriers of mutations, the level of enzyme activity cannot be used alone for carrier detection
medicine
-
analysis of mutations identified in patients with mucopolysaccharidosis type II. Mutations lead to aberrant precursor forms and loss of normal maturation of precursor. Mutant enzymes exhibit 2-4% of wild-type activity
medicine
-
analysis of 11 patients with mutations in the IDS gene leading to mucopolysaccharidosis type II. Structural alteration in the IDS protein results in its rapid degradation and/or insufficiency in processing
medicine
-
characterization of three mucopolysaccharidosis II patients with multiple aberrant transcripts due to three different point mutations. Mutations lead to production of only abnormally spliced transcripts (c.418+1G>C) or to abnormally spliced transcripts in addition to correctly spliced transcripts bearing the respective missence mutation (c.419G>T, and c.245C>T)
medicine
-
early treatment of mucopolysaccharidosis type II mice with one systemic injection of AAV2/5CMV-hIDS results in prolonged and high levels of circulating IDS that can efficiently and simultaneously rescue both visceral and central nervous system defects for up to 18 months after therapy
medicine
-
cognitive involvement is indicative of more severe disease and lower life expectancy in patients with mucopolysaccharidosis type II caused by a deficiency of iduronate-2-sulfatase: median age at death is significantly lower in patients who died in or before 1985 compared with those who died after 1985. Data from patients who died after 1985 may serve as a control in analyses of the effects of enzyme replacement therapy with idursulfase on mortality in patients with mucopolysaccharidosis type II. Idursulfase does not cross the blood-brain barrier in therapeutic quantities
medicine
-
measurement of plasma and/or leukocyte IDS activities does not discriminate adequately between mucopolysaccharidosis type II carriers and non-carriers
medicine
-
efficacy of cord blood stem cell transplantation for Hunter disease (deficiency of IDS) is judged to be insufficient for the brain at 10 months post-therapy, but the pathological detection of donor-derived cells in the brain parenchyma suggests the potential of hematopoietic stem cell transplantation for treatment of neurological symptoms in Hunter disease
medicine
-
idursulfase treatment appears to be safe and effective in adult Japanese patients with attenuated Mucopolysaccharidosis II
medicine
-
in humans, the inherited deficiency of the enzyme activity results in mucopolysaccharidosis type II, the Hunter syndrome
medicine
-
animal model for mucopolysaccharidosis
medicine
-
use of enzyme-replacement therapy with recombinant human iduronate-2-sulfatase as a specific treatment for Hunter syndrome. Reductions in liver and spleen volume and in urinary glycoaminoglycan excretion in patients treated with idursulfase. In clinical trials, idursulfase is well tolerated, but in in some patients life-threatening anaphylactic reactions during infusion of idursulfase
additional information
-
improvement of the total activity of recombinant IDS-Like at 3 litre bioreactor in glycerol as carbon source. Clone IDS28 of Pichia pastoris expressing IDS-Like employed for low-scale production of the recombinant enzyme in a saline culture media without phosphate. Biological activity is about 1.73 to 7times higher in batch culture than the result obtained with the same clone in shake flask culture