Information on EC 2.8.2.23 - [heparan sulfate]-glucosamine 3-sulfotransferase 1

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.8.2.23
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RECOMMENDED NAME
GeneOntology No.
[heparan sulfate]-glucosamine 3-sulfotransferase 1
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine = adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
show the reaction diagram
This enzyme differs from the other [heparan sulfate]-glucosamine 3-sulfotransferases, EC 2.8.2.29: [heparan sulfate]-glucosamine 3-sulfotransferase 2 and EC 2.8.2.30: [heparan sulfate]-glucosamine 3-sulfotransferase 3 by being the most selective for a precursor of the antithrombin-binding site
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
sulfate group transfer
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
heparan sulfate biosynthesis (late stages)
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Glycosaminoglycan biosynthesis - heparan sulfate / heparin
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SYSTEMATIC NAME
IUBMB Comments
3'-phosphoadenylyl-sulfate:[heparan sulfate]-glucosamine 3-sulfotransferase
This enzyme differs from the other [heparan sulfate]-glucosamine 3-sulfotransferases [EC 2.8.2.29 ([heparan sulfate]-glucosamine 3-sulfotransferase 2) and EC 2.8.2.30 ([heparan sulfate]-glucosamine 3-sulfotransferase 3)] by being the most selective for a precursor of the antithrombin-binding site. It has a minimal acceptor sequence of: -> GlcNAc6S-> GlcA-> GlcN2S*+/-6S-> IdoA2S-> GlcN2S-> , the asterisk marking the target (symbols as in {iupac/2carb/38::2-Carb-38}) using +/- to mean the presence or absence of a substituent, and > to separate a predominant structure from a minor one. Thus Glc(N2S > NAc) means a residue of glucosamine where the N carries a sulfo group mainly but occasionally an acetyl group.) [1-4]. It can also modify other precursor sequences within heparan sulfate but this action does not create functional antithrombin-binding sites. These precursors are variants of the consensus sequence: -> Glc(N2S > NAc)+/-6S-> GlcA-> GlcN2S*+/-6S-> GlcA > IdoA+/-2S-> Glc(N2S/NAc)+/-6S-> [5]. If the heparan sulfate substrate lacks 2-O-sulfation of GlcA residues, then enzyme specificity is expanded to modify selected glucosamine residues preceded by IdoA as well as GlcA [6].
CAS REGISTRY NUMBER
COMMENTARY hide
118113-79-4
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
isozymes gD-type-3-OST-4 and gD-type-3-OST-1
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3'-phosphoadenosine 5'-phosphosulfate + heparan sulfate-glucosamine
heparan sulfate 3-O-sulfo glucosamine + adenosine 3',5'-bisphosphate
show the reaction diagram
3'-phosphoadenylyl sulfate + GlcA-beta-(1->4)-GlcNS6S-beta-(1->4)-GlcA-beta-(1->4)-GlcNS6S-alpha-(CH2)5NH2
adenosine 3',5'-bisphosphate + GlcA-beta-(1->4)-GlcNS3S6S-beta-(1->4)-GlcA-beta-(1->4)-GlcNS6S-alpha-(CH2)5NH2
show the reaction diagram
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?
3'-phosphoadenylyl sulfate + GlcA-beta-(1->4)-GlcNS6S-beta-(1->4)-IdoA-beta-(1->4)-GlcNS6S-alpha-(CH2)5NH2
adenosine 3',5'-bisphosphate + GlcA-beta-(1->4)-GlcNS3S6S-beta-(1->4)-IdoA-beta-(1->4)-GlcNS6S-alpha-(CH2)5NH2
show the reaction diagram
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?
3'-phosphoadenylyl sulfate + GlcA-beta-(1->4)-GlcNS6S-beta-(1->4)-IdoA-beta-(1->4)-GlcNS6S-beta-(1->4)-GlcA-beta-(1->4)-GlcNS6S-alpha-(CH2)5NH2
adenosine 3',5'-bisphosphate + GlcA-beta-(1->4)-GlcNS3S6S-beta-(1->4)-IdoA-beta-(1->4)-GlcNS3S6S-beta-(1->4)-GlcA-beta-(1->4)-GlcNS6S-alpha-(CH2)5NH2
show the reaction diagram
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?
3'-phosphoadenylyl sulfate + GlcA-beta-(1->4)-GlcNS6S-beta-(1->4)-IdoA2S-beta-(1->4)-GlcNS6S-alpha-(CH2)5NH2
adenosine 3',5'-bisphosphate + GlcA-beta-(1->4)-GlcNS3S6S-beta-(1->4)-IdoA2S-beta-(1->4)-GlcNS6S-alpha-(CH2)5NH2
show the reaction diagram
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?
3'-phosphoadenylyl sulfate + IdoA-beta-(1->4)-GlcNS6S-beta-(1->4)-IdoA-beta-(1->4)-GlcNS6S-alpha-(CH2)5NH2
adenosine 3',5'-bisphosphate + IdoA-beta-(1->4)-GlcNS3S6S-beta-(1->4)-IdoA-beta-(1->4)-GlcNS6S-alpha-(CH2)5NH2
show the reaction diagram
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?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
show the reaction diagram
3-phosphoadenylylsulfate + GlcNSO3(6-OSO3)-GlcA-GlcNSO3(6-OSO3)-IdoA(2-OSO3)-GlcNSO3(6-OSO3)
adenosine 3',5'-bisphosphate + GlcNSO3(6-OSO3)-GlcA-GlcNSO3(3,6-bisOSO3)-IdoA(2-OSO3)-GlcNSO3(6-OSO3)
show the reaction diagram
3-phosphoadenylylsulfate + heparan sulfate
adenosine 3',5'-bisphosphate + ?
show the reaction diagram
3-phosphoadenylylsulfate + heparin-glucosamine
?
show the reaction diagram
3-phosphoadenylylsulfate + heparin-glucosamine
adenosine 3',5'-bisphosphate + heparin-glucosamine 3-O-sulfate
show the reaction diagram
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
3'-phosphoadenosine 5'-phosphosulfate + heparan sulfate-glucosamine
heparan sulfate 3-O-sulfo glucosamine + adenosine 3',5'-bisphosphate
show the reaction diagram
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
show the reaction diagram
3-phosphoadenylylsulfate + heparin-glucosamine
?
show the reaction diagram
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Na+
the enzyme contains sodium
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
chondriotin sulfate A
15% inhibition at 0.5 mg/ml
low affinity heparin
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partial inhibition at 0.006 mM, complete inhibition at 0.05 mM
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additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5-aza-2'-deoxycytidine
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exposure of chondrosarcoma cells to the DNA-methyltransferase inhibitor 5-Aza-dc up-regulates expression of 3-OST1 mRNA
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.01
3'-phosphoadenosine 5'-phosphosulfate
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wild type
0.006
GlcNSO3(6-OSO3)-GlcA-GlcNSO3(6-OSO3)-IdoA(2-OSO3)-GlcNSO3(6-OSO3)
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pH 7.4, 37°C
additional information
additional information
affinity and kinetic analysis of the interaction of wild-type 3-OST-1 and 3-OST-1 mutants E90Q and R276A with heparan sulfate, overview
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0013
low affinity heparin
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pH 7.4, 37°C
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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gD-type-3-OST-4 is one of the major enzymes
Manually annotated by BRENDA team
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H-EMC-SS chondrosarcoma cell
Manually annotated by BRENDA team
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mouse embryonal carcinoma cells
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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transmembrane enzyme with a short cytoplasmic tail at the N-terminus
Manually annotated by BRENDA team
additional information
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subcellular localization of HS3ST-2 in neurons, overview
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Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30000
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SDS-PAGE
37000
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acetylated protein
49825
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x * 49825, recombinant gD-type-3-OST-4, sequence calculation
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
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x * 49825, recombinant gD-type-3-OST-4, sequence calculation
additional information
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gD-type-3-OST-4 contains a short N-terminal cytoplasmic tail, a hydrophobic membrane spanning segment, and a SPLAG domain, the cytoplasmic tail contains a polyproline stretch, possibly involved in protein-protein interactions
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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acetylation
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ternary complex of 3-OST-1/3’-phosphoadenosine 5’-phosphate with an acceptor heptasaccharide substrate, microbatch technique, using 23.6 mM Tris (pH 7.5), 142 mM NaCl, 0.1 M sodium citrate (pH 5.5) and 20% (w/v) PEG 3000
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
glutathione Sepharose 4B resin column chromatography and Superdex 200 gel filtration
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recombinant protein
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recombinant protein from Escherichia coli
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Toyopearl AF-heparin 650M column chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
3-OST1 cDNA is inserted into the expression vector pCDNA3.1 for transfection of HEMC cells
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DNA and amino acid sequence determination and analysis and developmental expression analysis of the 3-OST gene family, sequence comparisons, phylogentic analysis, overview
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expressed in CHO cells
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expressed in CHO-K1 cells
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expressed in CHO-S, Dual-29, Dual-10, and CHO-gt31 cells
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expressed in Escherichia coli BL21 (DE3)-CodonPlusRIL cells
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expressed in Sf-9 cells; expression in Sf9 cells and Escherichia coli strain BL21-DE3
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expressed in Sf9 insect cells
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expression in Escherichia coli strain BL21(DE3)RIL
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expression of wild-type and mutant 3-OST-1 in Escherichia coli
gD-type-3-OST-4, DNA and amino acid sequence determination and sequence comparisons, neuronal tissue expression analysis, expression in CHO cells
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HS3ST-2 gene, expression in neurons, expression analysis in vivo, overview
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
exposure of chondrosarcoma cells to 5-aza-2'-deoxycytidine up-regulates expression of 3-OST1 mRNA
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D95A
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0.0% of the wild type activity
D95N
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8.1% of the wild type activity
E76A
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30.7% of the wild type activity
E76Q
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15.6% of the wild type activity
E88A
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63.7% of the wild type activity
E90A
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0.0% of the wild type activity
E98A
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65.6% of the wild type activity
H168A
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the mutant shows 51.1% activity compared to the wild type enzyme
H168E
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the mutant shows 19.1% activity compared to the wild type enzyme
H271A
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109.0% of the wild type activity
H271F
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42.0% of the wild type activity
H92A
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0.0% of the wild type activity
H92F
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0.0% of the wild type activity
K123A
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0.2% of the wild type activity
K132A
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49.1% of the wild type activity
K171A
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the mutant shows 83.9% activity compared to the wild type enzyme
K274A
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17.4% of the wild type activity
K284STP
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truncated b3-OST-1 mutant, lacks C-terminal region from residue 284 to 307, exhibits a 200fold reduction in sulfotransferase activity
K68A
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0.1% of the wild type activity
N167A
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the mutant shows 40.4% activity compared to the wild type enzyme
N89A
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69.5% of the wild type activity
N89D
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74.4% of the wild type activity
Q163A
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34.0% of the wild type activity
R197A
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95.0% of the wild type activity
R268A
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the mutant shows 7.2% activity compared to the wild type enzyme
R67A
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1.2% of the wild type activity
R67E
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1.1% of the wild type activity
R72A
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7.0% of the wild type activity
R72E
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0.0% of the wild type activity
S273A
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99.6% of the wild type activity
V164E
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the mutant shows 20.3% activity compared to the wild type enzyme
W96A
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91.6% of the wild type activity
W96F
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69.1% of the wild type activity
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
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usefulness of HS3ST-2 as a genetic marker for TrkC-positive mechanosensory neurons
medicine
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the results provide evidence for specific epigenetic regulation of 3-OST genes resulting in altered heparan sulfate proteoglycans and point to a defect of heparan sulfate-3-O-sulfation as a factor in cancer progression