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Literature summary for 2.8.2.23 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 | O14792 | - |
- |
| Homo sapiens | Q8IZT8 | - |
- |
| Homo sapiens | Q96QI5 | - |
- |
| Homo sapiens | Q9Y661 | - |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| cerebellum | - |
Homo sapiens | - |
| cerebellum | high expression level | Homo sapiens | - |
| cerebral cortex | - |
Homo sapiens | - |
| cerebral cortex | high expression level | Homo sapiens | - |
| colon | - |
Homo sapiens | - |
| heart | - |
Homo sapiens | - |
| kidney | - |
Homo sapiens | - |
| liver | - |
Homo sapiens | - |
| lung | - |
Homo sapiens | - |
| pancreas | - |
Homo sapiens | - |
| placenta | - |
Homo sapiens | - |
| skeletal muscle | high expression level | Homo sapiens | - |
| small intestine | - |
Homo sapiens | - |
| spleen | - |
Homo sapiens | - |
| spleen | high expression level | Homo sapiens | - |
| stomach | - |
Homo sapiens | - |
| testis | - |
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 |
| HS3ST1 | - |
Homo sapiens |
| HS3ST4 | - |
Homo sapiens |
| HS3ST5 | - |
Homo sapiens |
| HS3ST6 | - |
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 |
| Homo sapiens | increasing TRF2 level leads to an upregulation of HS3ST4 gene expression | up |
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 | 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 HS3ST1 gene in chondrosarcoma. Exposure to a demethylating agent restores its expression, confirming that aberrant methylation has affected its transcription | 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 HS3ST4 in MDA-MB-231 cells leads to an increase in cell viability and invasion, MDA-MB-231 cells carrying HS3ST4 expression display a significant increase in proliferation and survival | 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 | isozymes HS3ST2, HS3ST3B, and HS3ST4 may exhibit a broader selectivity. The HS3ST4 gene is identified as a transcriptional target of TRF2, and increasing TRF2 level leads to an upregulation of HS3ST4 gene expression. Exogenous expression of either TRF2 or HS3ST4 in various tumor cell lines similarly results in increased tumor growth in xenografted mice, which suggests that the expression of this enzyme may be part of a pro-oncogenic pathway. 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 | Homo sapiens |
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