Any feedback?
Literature summary for 3.2.1.166 extracted from
- The role of heparanase and sulfatases in the modification of heparan sulfate proteoglycans within the tumour microenvironment and opportunities for novel cancer therapeutics (2014), Front. Oncol., 4, 195.
Application
| Application | Comment | Organism |
|---|---|---|
| pharmacology | targeting enzymes that degrade heparan sulfate proteoglycans highlights one approach to maintain normal tissue architecture, inhibit tumor progression, and block metastasis | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| oligomanurarate sulfate | JG3, a marine-derived oligosaccharide and a heparanase inhibitor | Homo sapiens |  |
| PG545 | a synthetic, potent competitive inhibitor of heparanase with significant anti-tumor, anti-angiogenic, and anti-metastatic activity in a variety of animal models | Homo sapiens | |
| PI-88 | inhibits primary tumor growth of invasive rat mammary adenocarcinoma, metastasis, and reduced vascularity of these tumors while demonstrating significant anti-tumor activity in the pancreatic neuroendocrine RIP2-Tag2 model and in models of leukemia | Homo sapiens | |
| roneparstat | is an N-acetylated, glycol-splitheparin,which inhibits heparanase, downregulates HGF, VEGF, and MMP-9 expression and suppresses angiogene-sis. Roneparstat also diminishes heparanase-induced shedding of syndecan-1, which is known to be a potent promoter of myeloma | Homo sapiens | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cell surface | - |
Homo sapiens | 9986 | - |
| cytoplasm | - |
Homo sapiens | 5737 | - |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 8000 | - |
1 * 50000 + 1 * 8000, SDS-PAGE | Homo sapiens |
| 50000 | - |
1 * 50000 + 1 * 8000, SDS-PAGE | Homo sapiens |
| 65000 | - |
1 * 65000, precursor polypeptide, SDS-PAGE | Homo sapiens |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | Homo sapiens | heparanase is an endo-glycosidase that cleaves the heparan sulfate polymers at a limited number of sites within the chain releasing smaller fragments of 10-20 sugar units from heparan sulfate proteoglycan complexes | ? | - |
? | |
| syndecan-1 + H2O | Homo sapiens | heparanase promotes the activity of this mitogenic protein by removing the heparan sulfate chains from syndecan-1 leaving the deglycanated heparan sulfate proteoglycans as the active receptor for lacritin | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
single gene | - |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| proteolytic modification | the 65 kDa precursor polypeptide that is enzymatically inactive. Proteolytic excision by cathepsin L of a 48 amino acid peptide yields an active heterodimer comprising 8 and 50 kDa subunits | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| acute myeloid leukemia cell | heparanase protein is detected primarily within the cytoplasm of the cells, indicating that the enzyme is produced and stored within the cytoplasm of myeloid cells, with limited expression on the cell surface | Homo sapiens | - |
| adenocarcinoma cell | overexpression of heparanase in pancreatic adenocarcinomas | Homo sapiens | - |
| breast cancer cell | - |
Homo sapiens | - |
| carcinoma cell | activity and expression of the enzyme is modified in cancer tissue compared to control tissue, high expression levels in primary tumors and lymph nodes, detailed overview | Homo sapiens | - |
| cervical cancer cell | - |
Homo sapiens | - |
| epithelial cell | - |
Homo sapiens | - |
| gastric cancer cell | - |
Homo sapiens | - |
| head and neck cancer cell | - |
Homo sapiens | - |
| lymph node | - |
Homo sapiens | - |
| mononuclear cell | leukemic | Homo sapiens | - |
| ovary cancer cell | - |
Homo sapiens | - |
| pancreas | - |
Homo sapiens | - |
| renal tubule | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | heparanase is an endo-glycosidase that cleaves the heparan sulfate polymers at a limited number of sites within the chain releasing smaller fragments of 10-20 sugar units from heparan sulfate proteoglycan complexes | Homo sapiens | ? | - |
? | |
| syndecan-1 + H2O | heparanase promotes the activity of this mitogenic protein by removing the heparan sulfate chains from syndecan-1 leaving the deglycanated heparan sulfate proteoglycans as the active receptor for lacritin | Homo sapiens | ? | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| heterodimer | 1 * 50000 + 1 * 8000, SDS-PAGE | Homo sapiens |
| monomer | 1 * 65000, precursor polypeptide, SDS-PAGE | Homo sapiens |
General Information
| General Information | Comment | Organism |
|---|---|---|
| metabolism | key enzymes sulfatases and heparanase of the pathway actively influence cancer cell proliferation, signaling, invasion, and metastasis | Homo sapiens |
| additional information | sequence homology modeling indicates that heparanase contains a TIM barrel fold, which incorporates the two heparan sulfate-binding regions (residues 158-162 and 270-280) and the catalytic residues (Glu225 and Glu343) of the active site. The C-terminus of the protein forms a discrete domain, which has non-catalytic properties and is involved in a heparanase-mediated signaling function that is distinct from its enzymatic activity | Homo sapiens |
| physiological function | role of heparanase in the modification of heparan sulfate proteoglycans within the tumour microenvironment, overview. Involvement of heparanase in the metastatic extravasation of tumor cells and invasion of immune cells | Homo sapiens |
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
