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Information on EC 2.8.2.29 - [heparan sulfate]-glucosamine 3-sulfotransferase 2 and Organism(s) Homo sapiens
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2.8.2.29 [heparan sulfate]-glucosamine 3-sulfotransferase 2IUBMB Comments
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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The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
hs3st2, 3-ost-2, 3-o-sulfotransferase-2, 3-ost2, heparan sulfate 3-o-sulfotransferase 2, heparan sulfate (glucosamine) 3-o-sulfotransferase 2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
3-OST-2
glucosaminyl 3-O-sulfotransferase 3a,3b
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heparan sulfate 3-O-sulfotransferase 2
heparan sulfate D-glucosaminy 3-O-sulfotransferase
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HS3ST2
3-OST-2
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HS3ST2
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
sulfate group transfer
sulfate group transfer
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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.
CAS REGISTRY NUMBER
COMMENTARY
183257-54-7
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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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-
-
?
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
-
-
-
?
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'-diphosphate + [heparan sulfate]-glucosamine 3-sulfate
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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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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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-
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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-
?
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 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
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
-
-
-
-
?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
-
-
-
?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
-
-
-
-
?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
-
-
-
?
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'-diphosphate + [heparan sulfate]-glucosamine 3-sulfate
-
does not make active heparan sulfate, transfers sulfate to GlcA2S-GlcNS and IdoA2S-GlcNS
-
?
additional information
?
-
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
-
-
?
additional information
?
-
-
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
-
-
?
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
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
primary macrophages. HS3ST2 is highly expressed in non-activated macrophages
additional information
additional information
isozyme HS3ST2 is not expressed in cell lines representative of the different molecular breast cancer subgroups
additional information
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isozyme HS3ST2 is not expressed in cell lines representative of the different molecular breast cancer subgroups
additional information
subcellular distribution of isozymes HS3ST2 and HS3ST3B is analysed by using overexpression systems in HeLa cells
additional information
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subcellular distribution of isozymes HS3ST2 and HS3ST3B is analysed by using overexpression systems in HeLa cells
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
additional information
the catalytic domain might support correct addressing of HS3ST2 to cell surface. Partial colocalization of HS3ST2 with syndecan-2 in HeLa cells and primary macrophages. Silencing the expression of this proteoglycan altered the localization of HS3ST2, which suggests that syndecan-2 is required to address the isozyme outside of the Golgi apparatus
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additional information
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the catalytic domain might support correct addressing of HS3ST2 to cell surface. Partial colocalization of HS3ST2 with syndecan-2 in HeLa cells and primary macrophages. Silencing the expression of this proteoglycan altered the localization of HS3ST2, which suggests that syndecan-2 is required to address the isozyme outside of the Golgi apparatus
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
both isozymes, HS3ST3B (EC 2.8.2.30) and HS3ST2, are differently expressed in monocytes and macrophages depending on the inflammatory environment
evolution
HS3STs represent the largest family of HS-modifying enzymes, and yet the reaction of 3-O-sulfation is the rarest maturation step, when compared to other sulfations. Seven HS3STs have been characterized in human, for which the expression is dependent on cell type and tissue environment
malfunction
expression of the genes encoding HS-modifying enzymes is frequently dysregulated in cancer and other diseases. The enzymes show either anti-oncogenic or tumor-promoting effects. The 5' region of the HS3ST2 gene is hypermethylated in tumor tissue but not in surrounding non-cancerous tissue. The expression level of HS3ST2 is markedly reduced in the cancer sample compared with the matched normal counterpart. Reversing methylation restores the expression of the enzyme, confirming the silencing effect of gene methylation. Moreover, HS3ST2 gene hypermethylation is detected in the majority of primary breast cancer samples analysed, and also in human colon, lung and pancreatic cancers. Hypermethylation s found at high frequency in gastric, breast, colorectal, prostate and cervix cancers, as well as in hematological neoplasms. In breast and cervix, hypermethylation of the HS3ST2 gene occurs early during malignant transformation, suggesting a correlation between HS3ST2 silencing and progression of the disease. The exogenous reexpression of HS3ST2 is efficient to inhibit cell migration, invasion and proliferation in various lung cancer cell lines. But the tumor size is not significantly different between patients with HS3ST2 gene hypermethylation and those without, in spite of the anti-proliferative property of HS3ST2 observed in vitro. Re-expression of HS3ST2 in MDA-MB-231 cells leads to an increase in cell viability and invasion, MDA-MB-231 cells carrying HS3ST2 expression display a significant increase in proliferation and survival
malfunction
influence of HS3ST2 overexpression on the CSC phenotype in breast cancer cell lines representative of the triple-negative (MDA-MB-231) and hormone-receptor positive subtype (MCF-7). The CD44+/CD24-/low phenotype is significantly reduced in MDA-MB-231 cells after overexpression of the enzyme, remaining unaltered in MCF-7 cells. Colony and spheroid formation are increased after HS3ST2 overexpression in MCF-7 cells. The phenotypic changes are associated with complex changes in the expression of the stemness-associated notch and Wnt-signaling pathways constituents, syndecans, heparanase and Sulf1. Heparan sulfotransferase subtype-specific impact of HS modifications on the CSC phenotype of triple-negative and hormone receptor positive breast cancer model cell lines. In MDA-MB-231 cells, ALDH1 activity increases from 2.88% in the control transfected cells to 5.36% after overexpression of HS3ST2 overexpressing cells
metabolism
heparan sulfate (HS) 3-O-sulfation can be catalysed by seven 3-sulfotransferases (HS3STs) in humans, but nevertheless it is the rarest modification in heparan sulfate (HS). Isozymes HS3ST2 and HS3ST3B (EC 2.8.2.30) exhibit the same activity in vitro. But they are differently expressed in macrophages depending on cell environment, which suggests that they may be involved in distinct cellular processes
metabolism
high sulfation degree of heparan mediates functional interactions with positively charged amino acids in proteins. 2-O-sulfation of iduronic acid and 3-O-sulfation of glucosamine in heparan sulfate (HS) are mediated by the sulfotransferases HS2ST and HS3ST, respectively, which are dysregulated in several cancers. Both sulfotransferases regulate breast cancer cell viability and invasion. The syndecan family of HSPGs and the Notch pathway are part of the regulatory circuit of HS sulfotransferases. The expression levels of several genes are altered by overexpression of HS3ST2, breast cancer cell transcriptome analysis, overview
metabolism
HS3ST-mediated 3-O-sulfation leads to at least two distinct forms of 3-O-sulfated motifs. HS3ST1 and HS3ST5 participate in the generation of anticoagulant-active HS/heparin sequences for antithrombin-III, while HS3ST2, HS3ST3A, HS3ST3B, HS3ST4, and HS3ST6 are described to provide the HS-binding motifs for the glycoprotein gD of herpes simplex virus-1 (HSV-1). HS3ST regulations in cancer cells, cell proliferation, and tumor progression, overview
physiological function
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enzyme expression in lung cancer cells H460 and H23 inhibits cell migration, invasion, cell proliferation
physiological function
the enzyme is involved in heparan sulfate biosynthesis
physiological function
isozymes HS3ST2, HS3ST3B, and HS3ST4 may exhibit a broader selectivity. Re-expression of HS3ST2 in MDA-MB-231 cells leads to an increase in cell viability and invasion, MDA-MB-231 cells carrying HS3ST2 expression display a significant increase in proliferation and survival. Consistent with a proinvasive phenotype, Erk1/2 and beta-catenin signalling is upregulated in HS3ST2-expressing cells in an HS-dependent manner. The tumor-promoting effects of HS3ST2, HS3ST3B, and HS3ST4 are related to sustained activation of Src, Akt, and NF-kappaB, and upregulation of the anti-apoptotic proteins survivin and XIAP. Importantly, all these signalling molecules have been well described to play a critical role in promoting tumor growth and resistance to apoptosis
physiological function
the sulfotransferase HS3ST2 regulates breast cancer cell viability and invasion. It catalyzes the 3-O-sulfation of glucosamine in heparan sulfate. 3-O-sulfation of glucosamine is the rarest heparan sulfate (HS) modification step, yet strongly mediating selective cellular processes
additional information
to date, only a few ligands are known to selectively interact with 3-O-sulfated motifs, whereas hundreds of HS-binding proteins have been identified
additional information
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to date, only a few ligands are known to selectively interact with 3-O-sulfated motifs, whereas hundreds of HS-binding proteins have been identified
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). HS3S2_HUMAN
367
1
41501
Swiss-Prot
Mitochondrion (Reliability: 4)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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
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
additional information
generation of a truncated mutant enzyme depleted of its catalytic domain. The mutant remains in the Golgi apparatus, while the wild-type full-length enzyme localizes in the plasma membrane
additional information
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generation of a truncated mutant enzyme depleted of its catalytic domain. The mutant remains in the Golgi apparatus, while the wild-type full-length enzyme localizes in the plasma membrane
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene HS3ST2, quantitative real-time PCR enzyme expression analysis, recombinant overexpression in MDA-MB-231 and MCF-7 cells, cell transcriptome analysis, overview. The expression levels of several genes are altered by overexpression of HS3ST2
gene HS3ST2, real-time RT-PCR expression analysis, functional recombinant overexpression of HS3ST2 in HeLa cells. Transfection with the plasmid encoding non-tagged HS3ST2 results in the production of 3-O-sulfated HS. HS3ST2-transfected HeLa cells are indeed capable of interacting with HSV-1 gD protein. Analysis of subcellular localization of the recombinant isozyme
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
exposure of chondrosarcoma cells to 5-aza-2'-deoxycytidine up-regulates expression of 3-OST2 mRNA
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expression of the genes encoding HS-modifying enzymes is frequently dysregulated in cancer and other diseases
the overall transcriptional activity of the main heparan sulfate biosynthesis-involved genes (EXT1, EXT2, NDST1, NDST2, GLCE, HS2ST1, HS3ST1, HS3ST2, HS6ST1, HS6ST2, SULF1, SULF2, HPSE) is decreased by 1.5-2fold in Grade II-III glioma (p < 0.01) and by 3-fold in Grade IV glioma (glioblastoma multiforme, GBM) (p < 0.05), as compared with the para-tumourous tissue
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
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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Silencing of the 3-OST-2 gene is present in a wide range of human cancers. Possible diagnostic and potentially therapeutic value.
medicine
-
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
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Shworak, N.W.; Liu, J.; Petros, L.M.; Zhang, L.; Kobayashi, M.; Copeland, N.G.; Jenkins, N.A.; Rosenberg, R.D.
Multiple isoforms of heparan sulfate D-glucosaminyl 3-O-sulfotransferase
J. Biol. Chem.
274
5170-5184
1999
Homo sapiens
Liu, J.; Shworak, N.W.; Sinay, P.; Schwartz, J.J.; Zhang, L.; Fritze, L.M.S.; Rosenberg, R.D.
Expression of heparan sulfate D-glucosaminyl 3-O-sulfotransferase isoforms reveals novel substrate specificities
J. Biol. Chem.
274
5185-5192
1999
Homo sapiens
Miyamoto, K.; Asada, K.; Fukutomi, T.; Okochi, E.; Yagi, Y.; Hasegawa, T.; Asahara, T.; Sugimura, T.; Ushijima, T.
Methylation-associated silencing of heparan sulfate D-glucosaminyl 3-O-sulfotransferase-2 (3-OST-2) in human breast, colon, lung and pancreatic cancers
Oncogene
22
274-280
2003
Homo sapiens
O'Donnell C.D.; Tiwari, V.; Oh, M.J.; Shukla, D.
A role for heparan sulfate 3-O-sulfotransferase isoform 2 in herpes simplex virus type 1 entry and spread
Virology
346 Iss 2
452-459
2005
Homo sapiens
O'Donnell, C.D.; Tiwari, V.; Oh, M.; Shukla, D.
A role for heparan sulfate 3-O-sulfotransferase isoform 2 in herpes simplex virus type 1 entry and spread
Virology
346
452-459
2006
Homo sapiens (Q9Y278), Homo sapiens
Bui, C.; Ouzzine, M.; Talhaoui, I.; Sharp, S.; Prydz, K.; Coughtrie, M.W.; Fournel-Gigleux, S.
Epigenetics: methylation-associated repression of heparan sulfate 3-O-sulfotransferase gene expression contributes to the invasive phenotype of H-EMC-SS chondrosarcoma cells
FASEB J.
24
436-450
2010
Homo sapiens
Hwang, J.A.; Kim, Y.; Hong, S.H.; Lee, J.; Cho, Y.G.; Han, J.Y.; Kim, Y.H.; Han, J.; Shim, Y.M.; Lee, Y.S.; Kim, D.H.
Epigenetic inactivation of heparan sulfate (glucosamine) 3-O-sulfotransferase 2 in lung cancer and its role in tumorigenesis
PLoS ONE
8
e79634
2013
Homo sapiens
Ushakov, V.; Tsidulko, A.; De La Bourdonnaye, G.; Kazanskaya, G.; Volkov, A.; Kiselev, R.; Kobozev, V.; Kostromskaya, D.; Gaytan, A.; Krivoshapkin, A.; Aidagulova, S.; Grigorieva, E.
Heparan sulfate biosynthetic system is inhibited in human glioma due to EXT1/2 and HS6ST1/2 down-regulation
Int. J. Mol. Sci.
18
2301
2017
Homo sapiens (Q9Y278)
Delos, M.; Foulquier, F.; Hellec, C.; Vicogne, D.; Fifre, A.; Carpentier, M.; Papy-Garcia, D.; Allain, F.; Denys, A.
Heparan sulfate 3-O-sulfotransferase 2 (HS3ST2) displays an unexpected subcellular localization in the plasma membrane
Biochim. Biophys. Acta
1862
1644-1655
2018
Homo sapiens (Q9Y278), Homo sapiens
Teixeira, F.; Vijaya Kumar, A.; Kumar Katakam, S.; Cocola, C.; Pelucchi, P.; Graf, M.; Kiesel, L.; Reinbold, R.; Pavao, M.; Greve, B.; Goette, M.
The heparan sulfate sulfotransferases HS2ST1 and HS3ST2 are novel regulators of breast Cancer stem-cell Properties
Front. Cell Dev. Biol.
8
559554
2020
Homo sapiens (Q9Y278)
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