Application | Comment | Organism |
---|---|---|
medicine | heparanase-1 is an approach towards developing new therapeutics suitable for the treatment of cancer or inflammatory diseases. The identification of only a single predominant functional heparanase suggests that if its activity can be inhibited, other heparanases may not be available to cover for it. Heparanase-inhibiting compounds might interfere with physiological processes such as wound healing and tissue-repair | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
oligomannurarate sulphate | - |
Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
extracellular | heparanase-1 is mostly an intracellular, lysosomal enzyme. Only in cases where the receptor-system is absent or defective, the enzyme accumulates extracellularly. The presence of extracellular (active) heparanase-1 seems to be tightly regulated and restricted by at least two independent mechanisms, on one hand by regulated secretion and on the other hand by lipoprotein receptor-related proteins mediated (re-)uptake | Homo sapiens | - |
- |
lysosome | heparanase-1 is mostly an intracellular, lysosomal enzyme. Only in cases where the receptor-system is absent or defective, the enzyme accumulates extracellularly. The enzyme is stored within the acidic compartments in a stable form. Active enzyme can be secreted from intracellular compartments in response to a proper and effective stimulus | Homo sapiens | 5764 | - |
nucleus | the latent (65000 Da) and active (50000 Da) forms of human heparanase-1 accumulate in the nucleus of non-transfected human breast carcinoma cells and in the nucleus of glioma cells that are transfected or uploaded with exogenous human heparanase-1. The amount of nuclear heparanase-1 is up to 7% of the total levels found in the cytosol | Homo sapiens | 5634 | - |
specific granule | in blood-borne cells, active heparanase-1 is stored in specific granules, but in response to chemoattractants or inflammatory stimuli it is redistributed to the cell surface and released by degranulation | Homo sapiens | 42581 | - |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
8000 | - |
1 * 50000 + 1 * 8000 | Homo sapiens |
50000 | - |
1 * 50000 + 1 * 8000 | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
heparan sulfate proteoglycan + H2O | Homo sapiens | role for heparanase-1 in tissue morphogenesis, regeneration and repair during embryonic development and in the adult. Heparanase-1 may contribute to these processes by its effects on remodelling of extracellular matrix, cell migration, adhesion and proliferation. Heparanase-1 contributes to tumour growth by supporting cell survival under stress conditions | heparan sulfate fragment + truncated heparan sulfate proteoglycan | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q9Y251 | - |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
glycoprotein | the enzyme contains six N-linked oligosaccharides | Homo sapiens |
proteolytic modification | heparanase-1 is synthesized as an inactive precursor of about 65000 Da that subsequently undergoes proteolytic cleavage, yielding 8000 Da and 50000 Da protein subunits that heterodimerize to form the active enzyme. The protein contains a putative N-terminal signal peptide (Met1-Ala35) and a C-terminal hydrophobic region (Pro515-Ile534) | Homo sapiens |
Purification (Comment) | Organism |
---|---|
- |
Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
blood serum | elevated levels of heparanasen activity are detected in sera and urine samples of patients suffering from diabetic nephropathy or aggressive metastatic disease | Homo sapiens | - |
bone marrow | elevated level of heparanase-activity in bone marrow plasma of myeloma patients | Homo sapiens | - |
breast cancer cell | express high levels of endogenous heparanase-1 | Homo sapiens | - |
capillary | elevated expression of human heparanase-1 protein occurs in endothelial cells of sprouting capillaries and small vessels in the vicinity of a tumour, but not of mature, quiescent blood vessels | Homo sapiens | - |
embryo | heparanase-1 mRNA and protein are expressed in the liver and colon of 18-week and 22-week human foetuses, but not in the corresponding mature tissues | Homo sapiens | - |
glioma cell | - |
Homo sapiens | - |
keratinocyte | under normal conditions, heparanase-1 expression is restricted primarily to placental trophoblasts, blood-borne cells and keratinocytes | Homo sapiens | - |
MCF-7 cell | - |
Homo sapiens | - |
additional information | highly metastatic cells and tumours often show elevated expression of heparanase-1 in comparison with their non-invasive counterparts and normal tissues | Homo sapiens | - |
placenta | under normal conditions, heparanase-1 expression is restricted primarily to placental trophoblasts, blood-borne cells and keratinocytes | Homo sapiens | - |
urine | elevated level of heparanase-activity is detected in sera and urine samples of patients suffering from diabetic nephropathy or aggressive metastatic disease | Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
heparan sulfate proteoglycan + H2O | role for heparanase-1 in tissue morphogenesis, regeneration and repair during embryonic development and in the adult. Heparanase-1 may contribute to these processes by its effects on remodelling of extracellular matrix, cell migration, adhesion and proliferation. Heparanase-1 contributes to tumour growth by supporting cell survival under stress conditions | Homo sapiens | heparan sulfate fragment + truncated heparan sulfate proteoglycan | - |
? | |
heparan sulfate proteoglycan + H2O | the enzyme is an endo-beta-D-glucuronidase producing glucuronic acid or an iduronic acid at the newly formed reducing terminus. Heparanase-1 cuts macromolecular heparin into fragments of 500020000 Da. Infrequent enzyme cleavage sites may be due to either the recognition of a single, unusual modification in the heparin/HS chains or the requirement of a specific extended carbohydrate sequence for the cleavage | Homo sapiens | heparan sulfate fragment + truncated heparan sulfate proteoglycan | - |
? | |
heparin + H2O | - |
Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
heterodimer | 1 * 50000 + 1 * 8000 | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
heparanase-1 | - |
Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
5.5 | 6 | - |
Homo sapiens |
pH Minimum | pH Maximum | Comment | Organism |
---|---|---|---|
3.5 | 7 | no significant activity below pH 3.5 and above pH 7.0 | Homo sapiens |