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Enzyme Nomenclature
Information on EC 2.8.2.29 - [heparan sulfate]-glucosamine 3-sulfotransferase 2
for references in articles please use BRENDA:EC2.8.2.29
Word Map on EC 2.8.2.29
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The enzyme appears in viruses and cellular organisms
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EC NUMBER 
COMMENTARY 
2.8.2.29
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RECOMMENDED NAME
GeneOntology No.
[heparan sulfate]-glucosamine 3-sulfotransferase 2
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine = adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
This enzyme sulfates the residues marked with an asterisk in sequences containing at least IdoA2S-GlcN*- or ?GlcA2S.GlcN*-. Preference for GlcN2S vs. unmodified GlcN has not yet been established. Additional structural features are presumably required for substrate recognition, since the 3-O-sulfated residue is of low abundance, whereas the above IdoA-containing sequence is quite abundant. This enzyme differs from the other, [heparan sulfate]-glucosamine 3-sulfotransferases by modifying selected glucosamines residues preceded by GlcA2S. EC 2.8.2.23, [heparan sulfate]-glucosamine 3-sulfotransferase 1, prefers GlcA or IdoA, whereas EC 2.8.2.30, [heparan sulfate]-glucosamine 3-sulfotransferase 3, prefers IdoAS
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
sulfate group transfer
sulfate group transfer
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
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SYSTEMATIC NAME
IUBMB Comments
3'-phosphoadenylyl-sulfate:[heparan sulfate]-glucosamine 3-sulfotransferase
This enzyme sulfates the residues marked with an asterisk in sequences containing at least -> IdoA2S-> GlcN*-> or -> GlcA2S-> GlcN*-> (symbols as in {iupac/2carb/38::2-Carb-38}). Preference for GlcN2S vs. unmodified GlcN has not yet been established. Additional structural features are presumably required for substrate recognition, since the 3-O-sulfated residue is of low abundance, whereas the above IdoA-containing sequence is quite abundant. This enzyme differs from the other [heparan sulfate]-glucosamine 3-sulfotransferases by modifying selected glucosamine residues preceded by GlcA2S; EC 2.8.2.23 ([heparan sulfate]-glucosamine 3-sulfotransferase 1) prefers GlcA or IdoA, whereas EC 2.8.2.30 ([heparan sulfate]-glucosamine 3-sulfotransferase 3) prefers IdoA2S.
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CAS REGISTRY NUMBER
COMMENTARY
183257-54-7
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
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3-O-sulfotransferase-2-generated heparan sulfate serves as a receptor during herpes simplex virus type-1 entry and spread. The enzyme plays a role in HSV-1 pathogenesis
physiological function
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isoform 3-OST-2 mediates herpes simplex virus-1 entry and spread
physiological function
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enzyme expression in lung cancer cells H460 and H23 inhibits cell migration, invasion, cell proliferation
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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
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-diphosphate + [heparan sulfate]-glucosamine 3-sulfate
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
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?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
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i.e. HSgD+, 3-O-sulfated motifs that bind the gD envelope protein of Herpes simplex virus 1 mediating the viral cellular entry, overview, i.e. HSgD+, 3-O-sulfated motifs that bind the gD envelope protein of Herpes simplex virus 1
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?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
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?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
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-
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?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-diphosphate + [heparan sulfate]-glucosamine 3-sulfate
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-
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?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-diphosphate + [heparan sulfate]-glucosamine 3-sulfate
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does not make active heparan sulfate, transfers sulfate to GlcA2S-GlcNS and IdoA2S-GlcNS
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additional information
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heparan sulfate chains contain sulfated domains termed the HS fine structure, which gives HS specific binding affinities for extracellular ligands, heparan sulfate 3-O-sulfotransferases catalyze the transfer of sulfate groups to the 3-O position of glucosamine residues of heparan sulfate, a rare, but essential heparan sulfate chain modification required for HS fine structure
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additional information
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a gD-type-3-OST isozyme is essential for a conserved neurogenic signaling pathway regulated by Notch
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additional information
?
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modification of heparan sulfate and the ability of 3-OST-2 to generate receptors for both wild-types and some mutant forms of HSV-1, spreading of receptors mediating cell-to-cell fusion
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additional information
?
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HSV-1 glycoprotein gD, both the wild-type and the mutant Rid1 form, can interact with [heparan sulfate]-glucosamine 3-sulfate generated by HS 3-OST-2, overview
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NATURAL SUBSTRATES
NATURAL PRODUCTS
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
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-diphosphate + [heparan sulfate]-glucosamine 3-sulfate
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
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?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
-
-
i.e. HSgD+, 3-O-sulfated motifs that bind the gD envelope protein of Herpes simplex virus 1 mediating the viral cellular entry, overview
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?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
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?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
Q9Y278
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?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-diphosphate + [heparan sulfate]-glucosamine 3-sulfate
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-
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?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-diphosphate + [heparan sulfate]-glucosamine 3-sulfate
-
does not make active heparan sulfate, transfers sulfate to GlcA2S-GlcNS and IdoA2S-GlcNS
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-
additional information
?
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-
heparan sulfate chains contain sulfated domains termed the HS fine structure, which gives HS specific binding affinities for extracellular ligands, heparan sulfate 3-O-sulfotransferases catalyze the transfer of sulfate groups to the 3-O position of glucosamine residues of heparan sulfate, a rare, but essential heparan sulfate chain modification required for HS fine structure
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-
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additional information
?
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a gD-type-3-OST isozyme is essential for a conserved neurogenic signaling pathway regulated by Notch
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-
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additional information
?
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Q9Y278
modification of heparan sulfate and the ability of 3-OST-2 to generate receptors for both wild-types and some mutant forms of HSV-1, spreading of receptors mediating cell-to-cell fusion
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
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-OST2 mRNA
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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of trigeminal ganglia, gD-type-3-OST-2 is one of the major enzymes, highly located in neuronal cell bodies not in axons, overview
additional information
additional information
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developmental expression analysis of the 3-OST gene family, mRNA expression patterns in several tissues/organs throughout early zebrafish development, including early cleavage stages, somites, brain, internal body organ primordial, and pectoral fin development, overview
additional information
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neuronal tissue distribution of 3-O-sulfotransferases, overview
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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transmembrane enzyme with a short cytoplasmic tail at the N-terminus
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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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gD-type-3-OST-2, DNA and amino acid sequence determination and sequence comparisons, neuronal tissue expression analysis
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
exposure of chondrosarcoma cells to 5-aza-2'-deoxycytidine up-regulates expression of 3-OST2 mRNA
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
expression of 3-OST-2 renders CHO-K1 cell, which are normally resistant, susceptible to viral entry of wild-type and a Q27P mutant, Rid1, forms of HSV-1, requiring the gD receptors, Rid1 mutation at gD prevents its entry via some receptors including HVEM and 3-OS HS generated by 3-OST-3, overview
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
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Silencing of the 3-OST-2 gene is present in a wide range of human cancers. Possible diagnostic and potentially therapeutic value.
medicine
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possible role of 3-OST-2 in the spread of HSV-1 infection in the brain
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
medicine
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enzyme hypermethylation is an independent prognostic indicator for overall survival in node-negative stage I-II non-small cell lung cancer
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LINKS TO OTHER DATABASES (specific for EC-Number 2.8.2.29)
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