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Literature summary for 2.8.2.30 extracted from
- The emerging roles of heparan sulfate 3-O-sulfotransferases in cancer (2019), Front. Oncol., 9, 507 .
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine | Homo sapiens | - |
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate | - |
? |  |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | Q9Y662 | - |
- |
| Homo sapiens | Q9Y663 | - |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| colon | - |
Homo sapiens | - |
| heart | - |
Homo sapiens | - |
| kidney | - |
Homo sapiens | - |
| liver | - |
Homo sapiens | - |
| liver | high expression level | Homo sapiens | - |
| lung | - |
Homo sapiens | - |
| pancreas | - |
Homo sapiens | - |
| placenta | - |
Homo sapiens | - |
| placenta | high expression level | Homo sapiens | - |
| skeletal muscle | - |
Homo sapiens | - |
| small intestine | - |
Homo sapiens | - |
| spleen | - |
Homo sapiens | - |
| spleen | high expression level | Homo sapiens | - |
| stomach | - |
Homo sapiens | - |
| testis | - |
Homo sapiens | - |
| U-937 cell | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine | - |
Homo sapiens | adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| heparan sulfate 3-O-sulfotransferase | - |
Homo sapiens |
| HS3ST3A | - |
Homo sapiens |
| HS3ST3A1 | - |
Homo sapiens |
| HS3ST3B | - |
Homo sapiens |
| HS3ST3B1 | - |
Homo sapiens |
Expression
| Organism | Comment | Expression |
|---|---|---|
| Homo sapiens | expression of the genes encoding HS-modifying enzymes is frequently dysregulated in cancer and other diseases | additional information |
General Information
| General Information | Comment | Organism |
|---|---|---|
| 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 | Homo sapiens |
| 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. Hypermethylation in proximal regions of the HS3ST3A1 gene in chondrosarcoma. Exposure to a demethylating agent restores its expression, confirming that aberrant methylation has affected its transcription. Re-expression of HS3ST3A reduces the proliferative and migratory properties of chondrosarcoma cells, suggesting that silencing of this enzyme may have contributed to tumor cell growth and invasiveness. The HS3ST3A1 gene is epigenetically repressed in breast cancer cell lines representative of the different molecular subgroups, except in the human epidermal growth factor receptor 2-positive (HER2+) cell lines. Re-expression of the enzyme in luminal A-type MCF-7 and triple negative MDA-MB-231 cell lines reduces cell proliferation in vitro. HS3ST3A is also anti-proliferative in MDA-MB-231 cells. Overexpression of HS3ST3A does not have any effects on the proliferation of MDA-MB-231 cells | Homo sapiens |
| 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. Re-expression of HS3ST3B in MDA-MB-231 cells leads to an increase in cell viability and invasion, MDA-MB-231 cells carrying HS3ST3B expression display a significant increase in proliferation and survival. High expression of HS3ST3B in U937 leukemia cells enhances cell proliferation and survival, while its silencing has opposite effects | Homo sapiens |
| 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 | Homo sapiens |
| 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 | Homo sapiens |
| physiological function | isozyme HS3ST3A may have a restricted substrate specificity, making it incapable of synthesizing 3-O-sulfated heparan sulfate (HS) with a tumor-promoting property in MDA-MB-231 cells | Homo sapiens |
| physiological function | isozymes HS3ST2, HS3ST3B, and HS3ST4 may exhibit a broader selectivity. In pancreatic cancer cells, high level expression of HS3ST3B is reported to induce epithelial-mesenchymal transition (EMT) and to enhance cell invasiveness in vitro. HS3ST3B is related to an increase in the production of vascular endothelial growth factor (VEGF) and activation of downstream signalling pathways. 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. The tumor-promoting effect of HS3ST3B in leukemia cells is dependent on an autocrine activation of VEGF-dependent signalling pathways. HS3ST3B is described as a regulator of TGF-beta-mediated EMT in NSCLC cells. The tumor-promoting properties of HS3ST3B can be dependent on the formation of signalling complexes containing Nrp1 | Homo sapiens |
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