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Information on EC 3.1.6.13 - iduronate-2-sulfatase and Organism(s) Homo sapiens and UniProt Accession P22304
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3.1.6.13 iduronate-2-sulfataseSpecify your search results
Word Map
- 3.1.6.13
- mucopolysaccharidosis
- lysosomal
- glycosaminoglycans
-
x-linked
- dermatan
- heparan
-
multisystemic
-
sulfatases
-
hepatosplenomegaly
- medicine
- arylsulfatase
-
mpsii
-
x-chromosome
-
enzyme-replacement
- analysis
- synthesis
- alpha-l-iduronidase
-
neuronopathic
-
infusion-related
- drug development
-
6-minute
- dysostosis
- diagnostics
-
shire
- hurler
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
iduronate-2-sulfatase, idursulfase, iduronate sulfatase, iduronate 2-sulfatase, iduronate-2-sulphatase, elaprase, iduronate-2-sulfate sulfatase, 2-sulfo-l-iduronate 2-sulfatase, ids-like, ids-like enzyme, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
2-sulfo-L-iduronate 2-sulfatase
-
-
-
-
chondroitinsulfatase
-
-
-
-
iduronate sulfatase
iduronate sulfate sulfatase
-
-
-
-
iduronate-2-sulfatase
iduronate-2-sulfate sulfatase
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
-
-
-
-
iduronate sulfatase
-
-
-
-
iduronate-2-sulfatase
-
-
-
-
iduronate-2-sulfatase
-
-
iduronate-2-sulfate sulfatase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of sulfuric ester
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
L-iduronate-2-sulfate 2-sulfohydrolase
-
CAS REGISTRY NUMBER
COMMENTARY
50936-59-9
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
4-methylumbelliferyl-alpha-idopyranosiduronic acid 2-sulfate + H2O
4-methylumbelliferyl-alpha-iduronate + sulfate
-
-
-
?
4-methylumbelliferyl-alpha-iduronate 2-sulfate + H2O
4-methylumbelliferyl-alpha-iduronate + sulfate
-
-
-
?
4-methylumbelliferyl-alpha-iduronide 2-sulfate + H2O
4-methylumbelliferyl-alpha-iduronide + sulfate
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronate 2-sulfate + H2O
4-methylumbelliferol + L-iduronate 2-sulfate
-
-
-
?
4-methylumbelliferyl-alpha-iduronate 2-sulfate + H2O
4-methylumbelliferyl-alpha-iduronate + sulfate
-
-
-
-
?
4-methylumbelliferyl-alpha-iduronide-2-sulfate + H2O
4-methylumbelliferyl-alpha-iduronide + sulfate
-
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronate 2-sulfate + H2O
4-methylumbelliferol + L-iduronate 2-sulfate
-
artificial substrate
-
-
?
4-methylumbelliferyl-alpha-L-iduronide-2-sulfate + H2O
4-methylumbelliferyl-alpha-L-iduronide + sulfate
-
-
-
-
?
dermatan sulfate + H2O
dermatan + sulfate
-
-
135566, 135567, 135568, 135569, 135570, 135571, 135573, 135574, 135575, 135576, 135577, 135578, 691866
-
-
?
heparan sulfate + H2O
dermatan + sulfate
-
-
135566, 135567, 135568, 135569, 135570, 135571, 135573, 135574, 135575, 135576, 135577, 135578, 691866
-
-
?
heparin + H2O
desulfated heparin + sulfate
-
-
-
-
?
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
-
-
-
-
?
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
-
-
-
-
?
O-(alpha-L-idopyranosyluronic acid-2-sulfate)-(1-4)-2,5 anhydromannose-6-sulfate
?
-
-
-
?
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
-
-
-
-
?
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
-
-
-
-
?
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
-
-
-
-
?
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
-
-
-
-
?
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
-
-
-
-
?
additional information
?
-
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
?
-
-
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
?
-
mechanism follows a SN2 nucleophilic attack of the formylglycine FGH84 on the sulfur atom to generate the covalent formylglycine-S adduct, followed by elimination of bound sulfate and rehydration of the resultant formylglycine aldehyde. Residues H229, H138, D334 and K347 are likely to play active roles in proton transfer or activation of water during the reaction cycle
-
-
?
additional information
?
-
-
mechanism follows a SN2 nucleophilic attack of the formylglycine FGH84 on the sulfur atom to generate the covalent formylglycine-S adduct, followed by elimination of bound sulfate and rehydration of the resultant formylglycine aldehyde. Residues H229, H138, D334 and K347 are likely to play active roles in proton transfer or activation of water during the reaction cycle
-
-
?
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
?
-
-
mucopolysaccharidosis type II is a lysosomal storage disorder related to a deficiency in the enzyme iduronate-2-sulfatase
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
dermatan sulfate + H2O
dermatan + sulfate
-
-
-
-
?
heparan sulfate + H2O
dermatan + sulfate
-
-
-
-
?
heparin + H2O
desulfated heparin + sulfate
-
-
-
-
?
additional information
?
-
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
?
-
-
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
?
-
-
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
?
-
-
mucopolysaccharidosis type II is a lysosomal storage disorder related to a deficiency in the enzyme iduronate-2-sulfatase
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
effect of IDS on insulin secretion does not result from increased intracellular Ca2+ signaling
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
N-actetylglucosamine 6-sulfate-(1-4)-2,5-anhydro-D-mannitol 6-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
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0192
O-(alpha-L-idopyranosyluronic acid 2-sulfate)-(1-4)-2,5-anhydro-D-mannitol
-
-
0.0025 - 0.043
O-(alpha-L-idopyranosyluronic acid 2-sulfate)-(1-4)-2,5-anhydro-D-mannitol 6-sulfate
0.133 - 0.327
O-(alpha-L-idopyranosyluronic acid-2-sulfate)-(1-4)-2,5 anhydromannose-6-sulfate
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
0.0025 - 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
-
pool 2 in urine
0.013
O-(alpha-L-idopyranosyluronic acid 2-sulfate)-(1-4)-2,5-anhydro-D-mannitol 6-sulfate
-
form A
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
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.21
recombinant protein, pH not specified in the publication, temperature not specified in the publication
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
0.006
-
untreated neuronal cells, comparison to cells after adenoviral infection
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3.9 - 5.7
4.5 - 5.3
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
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
-
primary epithelial cell, highest activity of galacose 6-sulfatase and aryl sulfatase B of all the cell lines tested
-
IDS enzyme activity in mucopolysaccharidosis type II patient at 10 months post-cord blood stem cell transplantation
-
IDS enzyme activity in mucopolysaccharidosis type II patient at 10 months post-cord blood stem cell transplantation
-
remarkably low activity of arylsulfatase A, arylsulfatase B, galacose 6-sulfatase and steryl sulfatase, but not iduronate 2-sulfatase
-
primary myoepithelial cell, highest activity of steryl sulfatase and aryl sulfatase B of all the cell lines tested
-
remarkably low activity of arylsulfatase A, arylsulfatase B, galacose 6-sulfatase and steryl sulfatase, but not iduronate 2-sulfatase
additional information
-
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
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
additional information
-
development of an ELISA system to detect and quantify IDS with IgY antibodies, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
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
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
-
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
-
iduronate-2-sulfate sulfatase, IDS, deficiency causes the Hunter syndrome ormucopolysaccharidosis type II
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
-
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
-
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
-
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
-
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
-
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)
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
-
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
-
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). IDS_HUMAN
550
0
61873
Swiss-Prot
Secretory Pathway (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
55000
78000
-
x * 78000, precursor form, x * 46000-48000 and x * 55000, mature forms, SDS-PAGE
95000
additional information
-
the fusion protein is about 80 kDa larger than the heavy chain of the chimeric HIRMAb
55000
-
x * 78000, precursor form, x * 46000-48000 and x * 55000, mature forms, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
-
1 * 80000-90000, sucrose density gradient centrifugation, SDS-PAGE, after treatment with mercaptoethanol
?
-
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 * 78000, precursor form, x * 46000-48000 and x * 55000, mature forms, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
glycoprotein
proteolytic modification
-
proteolytic maturation of 78000 Da precursor form to 46000-48000 and 55000 Da mature forms
glycoprotein
deglycosylation with PNGase leads to a decrease in molecular mass from 76000 Da to 58000 Da
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
structural models of the wild type and mutant IDS proteins resulting from 131 missense mutations identified in patients with mucopolysaccharidosis MPS II. The amino acid substitutions causing MPS II are widely spread over the enzyme molecule and the structural changes of the enzyme protein are generally larger in the severe group than in the attenuated one. The structural changes influence the disease progression
structure with a covalently bound sulfate ion in the active site, to 2.3 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D148V
the mutation perturbs the structure or molecular interactions of the enzyme, leading to loss of enzyme activity and severe phenotype of disease
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
K227E
the mutation perturbs the structure or molecular interactions of the enzyme, leading to loss of enzyme activity and severe phenotype of disease
P86L
the mutation activates multiple cryptic splice sites, resulting in aberrantly spliced transcripts of IDS
R443X
the mutation produces truncated protein lacking 20% of the IDS protein, which leads to severe clinical presentations
W337X
the mutation produces truncated protein lacking 39% of the IDS protein, which leads to severe clinical presentations
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
C84S
-
artificial mutation in predicted active site. No enzymic acitivity, presence of both the precursor form and processed form of enzyme
C84T
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
L339R
-
the missense variant has stable mRNA but the residual enzyme activity remains 2.3% of wild type level
P86L
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
R468L
-
mutation identified in patient with mucopolysaccharidosis type II, severe phenotype. No residual activity, presence of precursor form of enzyme
R468Q
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
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
additional information
C84T
-
artificial mutation in predicted active site. No enzymic acitivity, presence of both the precursor form and processed form of enzyme
P86L
-
mutation identified in patient with mucopolysaccharidosis type II, severe phenotype. No residual activity, presence of precursor form of enzyme
R468Q
-
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
additional information
-
in 25 Hunter syndrome patients 20 mutations of the gene are identified of which 13 mutations are novel
additional information
-
K347T, N265I, 473delTCC, 533delTT mutations are identified in four out of 28 Hunter syndrome patients
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
-
R88H, R88P, T118I, 959delT, R468Q mutations are identified in Hunter syndrome patients
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
-
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
-
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
-
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
-
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
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
50
55
-
30 min, 50% loss of activity of form A, 45 min, 50% loss of activity of form B
50
-
pH 4.0, 0.1 M sodium acetate, 1% bovine serum albumin, 2 h, 50% inactivation
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
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
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
HIRMAb-IDS fusion protein purified by protein A affinity chromatography, to homogeneity
-
strategy for improving protein expression and purification of recombinant protein
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
-
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
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
although IDS transcript levels are reduced (51-71% normal) in Hunter syndrome patients, some wild-type IDS protein is detectable
-
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
-
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
-
presence of wild-type IDS mRNA-transcripts in Hunter syndrome patients, but no wild-type IDS genomic sequence detectable
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
direct assay for enzyme activity using substrate 4-methylumbelliferyl alpha-L-idopyranosiduronic acid 2-sulfate and LC-MS/MS based detection
medicine
synthesis
expression of protein in Pichia pastoris. The highest production of recombinant IDS is obtained at oxygen-limited conditions using a codon-optimized IDS cDNA.The purified enzyme shows a final activity of 12.45 nmol/mg/h. IDS shows high stability in human serum and is taken up by HEK-293 cells in a dose-dependent manner through mannose receptors
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
synthesis
-
expression and purification of enzyme from Escherichia coli, strategy for improving protein expression and purification
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
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
application of a combined assay for defects in iduronate-2-sulfatase (ID2S) leading to mucopolysaccharidosis II, and N-acetylgalactosamine-6-sulfatase (GALN) and N-acetylgalactosamine-4-sulfatase (ARSB) defects related to mucopolysaccharidosis IVA and MPS VI, respectively. The average enzyme activities of ID2S, GALN, and ARSB in random neonates are 19.6, 1.7, and 13.4 micromol/h/l, respectively. The average enzyme activities of ID2S, GALN, and ARSB in disease-affected individuals are 0.5, 0.3, and 0.3 micromol/h/l, respectively
medicine
structural models of the wild type and mutant IDS proteins resulting from 131 missense mutations identified in patients with mucopolysaccharidosis MPS II. The amino acid substitutions causing MPS II are widely spread over the enzyme molecule and the structural changes of the enzyme protein are generally larger in the severe group than in the attenuated one. The structural changes influence the disease progression
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
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
measurement of plasma and/or leukocyte IDS activities does not discriminate adequately between mucopolysaccharidosis type II carriers and non-carriers
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
medicine
-
effects of enzyme replacement therapy with iduronate 2-sulfatase on growth in young patients with mucopolysaccharidosis type II. Patients in group 1 received intravenous idursulfase at a standard dose of 0.58 mg/kg weekly for 52-288 weeks. The course of average growth curve for group 1 is very similar to growth pattern in group 2 naive to the enzyme. The average value of body height in subsequent years in group 1 is a little greater than in group 2, however, the difference is not statistically significant. In studied patients with mucopolysaccharidosis type II, idursulfase does not appear to alter the growth patterns
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Di Natale, P.; Ronsisvalle, L.
Identification and partial characterization of two enzyme forms of iduronate sulfatase from human placenta
Biochim. Biophys. Acta
661
106-111
1981
Homo sapiens
Yutaka, T.; Fluharty, A.L.; Stevens, R.L.; Kihara, H.
Purification and some properties of human liver iduronate sulfatase
J. Biochem.
91
433-441
1982
Homo sapiens
Wasteson, A.; Neufeld, E.F.
Iduronate sulfatase from human plasma
Methods Enzymol.
83
573-578
1982
Homo sapiens
Archer, I.M.; Harper, P.S.; Wusteman, F.S.
Multiple forms of iduronate 2-sulphate sulphatase in human tissues and body fluids
Biochim. Biophys. Acta
708
134-140
1982
Homo sapiens
Lissens, W.; Zenati, A.; Liebaers, I.
Polyclonal antibodies against iduronate 2-sulphate sulphatase from human urine
Biochim. Biophys. Acta
801
365-371
1984
Homo sapiens
Di Natale, P.; Daniele, A.
Iduronate sulfatase from human placenta
Biochim. Biophys. Acta
839
258-261
1985
Homo sapiens
Bach, G.; Eisenberg, F., Jr.; Cantz, M.; Neufeld, E.F.
The defect in the Hunter syndrome: deficiency of sulfoiduronate sulfatase
Proc. Natl. Acad. Sci. USA
70
2134-2138
1973
Homo sapiens
Sjoberg, I.; Fransson, L.A.; Matalon, R.; Dorfman, A.
Hunter's syndrome: a deficiency of L-idurono-sulfate sulfatase
Biochem. Biophys. Res. Commun.
54
1125-1132
1973
Homo sapiens
Bielicki, J.; Freeman, C.; Clements, P.R.; Hopwood, J.J.
Human liver iduronate-2-sulphatase. Purification, characterization and catalytic properties
Biochem. J.
271
75-86
1990
Homo sapiens
Bielicki, J.; Hopwood, J.J.; Wilson, P.J.; Anson, D.S.
Recombinant human iduronate-2-sulphatase: correction of mucopolysaccharidosis-type II fibroblasts and characterization of the purified enzyme
Biochem. J.
289
241-246
1993
Homo sapiens
Petruschka, L.; Zschiesche, M.; Bielicki, J.; Seidlitz, G.; Machill, G.; Hopwood, J.J.; Herrmann, F.H.
Mucopolysaccharidosis type II (Hunter syndrome): characterization of the iduronate-2-sulphatase in MPS II skin fibroblasts
J. Inherit. Metab. Dis.
17
89-92
1994
Homo sapiens
Millat, G.; Froissart, R.; Maire, I.; Bozon, D.
Characterization of iduronate sulphatase mutants affecting N-glycosylation sites and the cysteine-84 residue
Biochem. J.
326
243-247
1997
Homo sapiens
Villani, G.R.; Daniele, A.; Balzano, N.; Di Natale, P.
Expression of five iduronate-2-sulfatase site-directed mutations
Biochim. Biophys. Acta
1501
71-80
2000
Homo sapiens
Bonuccelli, G.; Di Natale, P.; Corsolini, F.; Villani, G.; Regis, S.; Filocamo, M.
The effect of four mutations on the expression of iduronate-2-sulfatase in mucopolysaccharidosis type II
Biochim. Biophys. Acta
1537
233-238
2001
Homo sapiens
Daniele, A.; Tomanin, R.; Villani, G.R.; Zacchello, F.; Scarpa, M.; Di Natale, P.
Uptake of recombinant iduronate-2-sulfatase into neuronal and glial cells in vitro
Biochim. Biophys. Acta
1588
203-209
2002
Homo sapiens, Rattus norvegicus
Kim, C.H.; Hwang, H.Z.; Song, S.M.; Paik, K.H.; Kwon, E.K.; Moon, K.B.; Yoon, J.H.; Han, C.K.; Jin, D.K.
Mutational spectrum of the iduronate 2 sulfatase gene in 25 unrelated Korean Hunter syndrome patients: identification of 13 novel mutations
Hum. Mutat.
21
449-450
2003
Homo sapiens
Pan, D.; Jonsson, J.J.; Braun, S.E.; McIvor, R.S.; Whitley, C.B.
"Supercharged Cells" for delivery of recombinant human iduronate-2-sulfatase
Mol. Genet. Metab.
70
170-178
2000
Homo sapiens
Parkinson, E.J.; Muller, V.; Hopwood, J.J.; Brooks, D.A.
Iduronate-2-sulphatase protein detection in plasma from mucopolysaccharidosis type II patients
Mol. Genet. Metab.
81
58-64
2004
Homo sapiens
Parkinson-Lawrence, E.; Turner, C.; Hopwod, J.; Brooks, D.
Analysis of normal and mutant iduronate-2-sulphatase conformation
Biochem. J.
386
395-400
2005
Homo sapiens (P22304), Homo sapiens
Dean, C.J.; Bockmann, M.R.; Hopwood, J.J.; Brooks, D.A.; Meikle, P.J.
Detection of mucopolysaccharidosis type II by measurement of iduronate-2-sulfatase in dried blood spots and plasma samples
Clin. Chem.
52
643-649
2006
Homo sapiens
Bhattacharyya, S.; Tobacman, J.K.
Steroid sulfatase, arylsulfatases A and B, galactose-6-sulfatase, and iduronate sulfatase in mammary cells and effects of sulfated and non-sulfated estrogens on sulfatase activity
J. Steroid Biochem. Mol. Biol.
103
20-34
2007
Homo sapiens
Lin, S.P.; Chang, J.H.; Lee-Chen, G.J.; Lin, D.S.; Lin, H.Y.; Chuang, C.K.
Detection of Hunter syndrome (mucopolysaccharidosis type II) in Taiwanese: biochemical and linkage studies of the iduronate-2-sulfatase gene defects in MPS II patients and carriers
Clin. Chim. Acta
369
29-34
2006
Homo sapiens
Chang, J.; Lin, S.; Chuang, C.; Lee-Chen, G.
Characterization of a novel p.S305P and a known c.1006+5G>C splice site mutation in human iduronate-2-sulfatase associated with mucopolysaccharidosis type II
Clin. Chim. Acta
384
167-170
2007
Homo sapiens
Alves, S.; Mangas, M.; Prata, M.J.; Ribeiro, G.; Lopes, L.; Ribeiro, H.; Pinto-Basto, J.; Lima, M.R.; Lacerda, L.
Molecular characterization of Portuguese patients with mucopolysaccharidosis type II shows evidence that the IDS gene is prone to splicing mutations
J. Inherit. Metab. Dis.
29
743-754
2006
Homo sapiens
Sukegawa-Hayasaka, K.; Kato, Z.; Nakamura, H.; Tomatsu, S.; Fukao, T.; Kuwata, K.; Orii, T.; Kondo, N.
Effect of Hunter disease (mucopolysaccharidosis type II) mutations on molecular phenotypes of iduronate-2-sulfatase: enzymatic activity, protein processing and structural analysis
J. Inherit. Metab. Dis.
29
755-761
2006
Homo sapiens
Lualdi, S.; Pittis, M.G.; Regis, S.; Parini, R.; Allegri, A.E.; Furlan, F.; Bembi, B.; Filocamo, M.
Multiple cryptic splice sites can be activated by IDS point mutations generating misspliced transcripts
J. Mol. Med.
84
692-700
2006
Homo sapiens
Lau, K.C.; Lam, C.W.
Molecular investigations of a novel iduronate-2-sulfatase mutant in a Chinese patient
Clin. Chim. Acta
392
8-10
2008
Homo sapiens
Keeratichamroen, S.; Ketudat Cairns, J.R.; Wattanasirichaigoon, D.; Wasant, P.; Ngiwsara, L.; Suwannarat, P.; Pangkanon, S.; Kuptanon, J.; Tanpaiboon, P.; Rujirawat, T.; Liammongkolkul, S.; Svasti, J.
Molecular analysis of the iduronate-2-sulfatase gene in Thai patients with Hunter syndrome
J. Inherit. Metab. Dis.
Suppl. 2
303-311
2008
Homo sapiens (P22304), Homo sapiens
Cordoba-Ruiz, H.; Poutou-Pinales, R.; Echeverri-Pena, O.; Algecira-Enciso, N.; Landazuri, P.; Saenz, H.; Barrera-Avellaneda, L.
Laboratory scale production of the human recombinant iduronate 2-sulfate sulfatase-Like from Pichia pastoris
Afr. J. Biotechnol.
8
1786-1792
2009
Homo sapiens
-
Polito, V.A.; Cosma, M.P.
IDS crossing of the blood-brain barrier corrects CNS defects in MPSII mice
Am. J. Hum. Genet.
85
296-301
2009
Homo sapiens
Piquer, S.; Casas, S.; Quesada, I.; Nadal, A.; Julia, M.; Novials, A.; Gomis, R.
Role of iduronate-2-sulfatase in glucose-stimulated insulin secretion by activation of exocytosis
Am. J. Physiol. Endocrinol. Metab.
297
E793-E801
2009
Homo sapiens
Lu, J.Z.; Hui, E.K.; Boado, R.J.; Pardridge, W.M.
Genetic engineering of a bifunctional IgG fusion protein with iduronate-2-sulfatase
Bioconjug. Chem.
21
151-156
2010
Homo sapiens
Lualdi, S.; Tappino, B.; Di Duca, M.; Dardis, A.; Anderson, C.J.; Biassoni, R.; Thompson, P.W.; Corsolini, F.; Di Rocco, M.; Bembi, B.; Regis, S.; Cooper, D.N.; Filocamo, M.
Enigmatic In Vivo iduronate-2-sulfatase (IDS) mutant transcript correction to wild-type in Hunter syndrome
Hum. Mutat.
31
E1261-E1285
2010
Homo sapiens
Jones, S.A.; Almassy, Z.; Beck, M.; Burt, K.; Clarke, J.T.; Giugliani, R.; Hendriksz, C.; Kroepfl, T.; Lavery, L.; Lin, S.P.; Malm, G.; Ramaswami, U.; Tincheva, R.; Wraith, J.E.; Wraith, J.E.
Mortality and cause of death in mucopolysaccharidosis type II-a historical review based on data from the Hunter Outcome Survey (HOS)
J. Inherit. Metab. Dis.
32
534-543
2009
Homo sapiens
Schwartz, I.V.; Pinto, L.L.; Breda, G.; Lima, L.; Ribeiro, M.G.; Mota, J.G.; Acosta, A.X.; Correia, P.; Horovitz, D.D.; Porciuncula, C.G.; Lipinski-Figueiredo, E.; Fett-Conte, A.C.; Sobrinho, R.P.; Norato, D.Y.; Paula, A.C.; Kim, C.A.; Duarte, A.R.; Boy, R.; Leistner-Segal, S.; Burin, M.G.; Giugliani, R.
Clinical and biochemical studies in mucopolysaccharidosis type II carriers
J. Inherit. Metab. Dis.
32
732-738
2009
Homo sapiens
Araya, K.; Sakai, N.; Mohri, I.; Kagitani-Shimono, K.; Okinaga, T.; Hashii, Y.; Ohta, H.; Nakamichi, I.; Aozasa, K.; Taniike, M.; Ozono, K.
Localized donor cells in brain of a Hunter disease patient after cord blood stem cell transplantation
Mol. Genet. Metab.
98
255-263
2009
Homo sapiens
Okuyama, T.; Tanaka, A.; Suzuki, Y.; Ida, H.; Tanaka, T.; Cox, G.; Eto, Y.; Orii, T.
Japan Elaprase Treatment (JET) study: idursulfase enzyme replacement therapy in adult patients with attenuated Hunter syndrome (Mucopolysaccharidosis II, MPS II)
Mol. Genet. Metab.
99
18-25
2010
Homo sapiens
Muenzer, J.; Beck, M.; Eng, C.M.; Escolar, M.L.; Giugliani, R.; Guffon, N.H.; Harmatz, P.; Kamin, W.; Kampmann, C.; Koseoglu, S.T.; Link, B.; Martin, R.A.; Molter, D.W.; Munoz Rojas, M.V.; Ogilvie, J.W.; Parini, R.; Ramaswami, U.; Scarpa, M.; Schwartz, I.V.; Wood, R.E.; Wraith, E.
Multidisciplinary management of Hunter syndrome
Pediatrics
124
e1228-e1239
2009
Homo sapiens
Lu, J.Z.; Boado, R.J.; Hui, E.K.; Zhou, Q.H.; Pardridge, W.M.
Expression in CHO cells and pharmacokinetics and brain uptake in the Rhesus monkey of an IgG-iduronate-2-sulfatase fusion protein
Biotechnol. Bioeng.
108
1954-1964
2011
Homo sapiens
Sosa, A.C.; Espejo, A.J.; Rodriguez, E.A.; Lizaraso, L.M.; Rojas, A.; Guevara, J.; Echeverri, O.Y.; Barrera, L.A.
Development of a sandwich enzyme linked immunosorbent assay (ELISA) for the quantification of iduronate-2-sulfate sulfatase
J. Immunol. Methods
368
64-70
2011
Homo sapiens
Morales-Alvarez, E.D.; Rivera-Hoyos, C.M.; Baena-Moncada, A.M.; Landazuri, P.; Poutou-Pinales, R.A.; Saenz-Suarez, H.; Barrera, L.A.; Echeverri-Pena, O.Y.
Low-scale expression and purification of an active putative iduronate 2-sulfate sulfatase-Like enzyme from Escherichia coli K12
J. Microbiol.
51
213-221
2013
Homo sapiens
Zuber, Z.; RodzynskaSwiatowska, A.; Jurecka, A.; Tylki-Szymanska, A.
The effect of recombinant human iduronate-2-sulfatase (idursulfase) on growth in young patients with mucopolysaccharidosis type II
PLoS ONE
9
e85074
2014
Homo sapiens
Pimentel, N.; Rodriguez-Lopez, A.; Diaz, S.; Losada, J.C.; Diaz-Rincon, D.J.; Cardona, C.; Espejo-Mojica, A.J.; Ramirez, A.M.; Ruiz, F.; Landazuri, P.; Poutou-Pinales, R.A.; Cordoba-Ruiz, H.A.; Almeciga-Diaz, C.J.; Barrera-Avellaneda, L.A.
Production and characterization of a human lysosomal recombinant iduronate-2-sulfatase produced in Pichia pastoris
Biotechnol. Appl. Biochem.
65
655-664
2018
Homo sapiens (P22304), Homo sapiens
Lee, K.; Jun, S.H.; Song, S.H.; Park, H.D.; Park, K.U.; Song, J.
Direct assay of iduronate-2-sulfatase for Hunter disease using UPLC-tandem mass spectrometry and fluorogenic substrate
Clin. Biochem.
48
1350-1353
2015
Homo sapiens (P22304)
Mashima, R.; Ohira, M.; Okuyama, T.; Tatsumi, A.
Quantification of the enzyme activities of iduronate-2-sulfatase, N-acetylgalactosamine-6-sulfatase and N-acetylgalactosamine-4-sulfatase using liquid chromatography-tandem mass spectrometry
Mol. Genet. Metab. Rep.
14
36-40
2018
Homo sapiens (P22304)
Demydchuk, M.; Hill, C.; Zhou, A.; Bunkoczi, G.; Stein, P.; Marchesan, D.; Deane, J.; Read, R.
Insights into Hunter syndrome from the structure of iduronate-2-sulfatase
Nat. Commun.
8
15786
2017
Homo sapiens (P22304), Homo sapiens
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