Heparanase
| Heparanase | ||
|---|---|---|
| Properties of human protein | ||
| Mass / length primary structure | 460 aa; 58 kDa | |
| Secondary to quaternary structure | Heterodimer | |
| Precursor | (540 aa; 65 kDa) | |
| Identifier | ||
| Gene names | HPSE ; HPR1; HPA; HPSE1; HSE1 | |
| External IDs | ||
| Enzyme classification | ||
| EC, category | 3.2.-.- , glycosidase | |
| Substrate | Heparan sulfate proteoglycans | |
| Products | Heparan sulfate + proteoglycans | |
| Occurrence | ||
| Parent taxon | Eukaryotes | |
| Orthologue | ||
| human | mouse | |
| Entrez | 10855 | 15442 |
| Ensemble | ENSG00000173083 | ENSMUSG00000035273 |
| UniProt | Q9Y251 | Q6YGZ1 |
| Refseq (mRNA) | NM_006665 | XM_982223 |
| Refseq (protein) | NP_006656 | XP_987317 |
| Gene locus | Chr 4: 84.43 - 84.48 Mb | Chr 5: 100.92 - 100.96 Mb |
| PubMed search | 10855 |
15442
|
Heparanase (synonyms: heparan sulfate endoglycosidase; endo-β-D-glucuronidase) is an enzyme produced by the body , an endoglycosidase , which specifically cleaves heparan sulfate chains from cell surface and basement membrane heparan sulfate proteoglycans . and in numerous important biological processes such as B. tumor invasion and metastasis is involved.
synthesis
Heparanase is initially formed as an inactive proenzyme of approx. 65 kDa. A 6 kDa fragment is proteolytically cut out of this proenzyme and the two 8 kDa and 50 kDa fragments formed form the active heterodimer . Heparanase splits heparan sulfate and heparin only at a few defined interfaces in the polysaccharide chain.
Biological importance and inhibition
Heparan sulfate -Proteoglykane (HS-PG) are a group of complex macromolecules that on the cell surface of most cells but also and above all in all basement membranes and in the extracellular matrix are expressed and, among other important tasks in the control of cell proliferation and differentiation have (e.g. as coreceptors of cytokines and growth factors ). In addition, HS-PG are important components of the basement membrane and control not only the exchange of substances (e.g. in the glomerular basement membrane), but also cell migration .
In the context of inflammatory and immune reactions, inflammatory and immune cells, i. H. Above all, neutrophils , monocytes and lymphocytes migrate from the blood vessels into the area of inflammation and therefore overcome the basement membranes. For the basement membrane passage it is necessary to degrade the basement membrane locally, especially the heparan sulfate chains of the HS-PG. Accordingly, the enzyme heparanase is expressed by a number of cell types, especially leukocytes, platelets, but also many tumor cells.
By inhibiting the heparanase, not only inflammatory reactions but also the invasion and metastasis of tumors can be inhibited. The high expression of heparanase by tumor cells is a prognostic marker e.g. B. in pancreatic carcinoma . The development of suitable heparanase inhibitors forms a new, interesting approach in tumor therapy , especially because there is only one gene for heparanase in humans .
The enzyme heparanase can also release cytokines and growth factors (e.g. bFGF) bound to heparan sulfate on cell surfaces, in the basement membrane, but especially in the extracellular matrix, and thus control processes such as angiogenesis but also wound healing and repair processes.
proof
An enzyme immunoassay has recently become available for measuring heparanase activity .
Web links
- Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB): Enzyme Nomenclature. Recommendations.
- ExPASy: Enzyme nomenclature database
Individual evidence
- ^ SB Peterson, J. Liu: Multi-faceted substrate specificity of heparanase. In: Matrix Biology. Volume 32, Number 5, June 2013, pp. 223-227, ISSN 1569-1802 . doi : 10.1016 / j.matbio.2013.02.006 . PMID 23499529 .
- ↑ I. Vlodavsky, RV Iozzo, RD Sanderson: heparanase: multiple functions in inflammation, diabetes and atherosclerosis. In: Matrix biology: journal of the International Society for Matrix Biology. Volume 32, Number 5, June 2013, pp. 220-222, ISSN 1569-1802 . doi : 10.1016 / j.matbio.2013.03.001 . PMID 23499526 .
- ↑ a b A. Meirovitz, R. Goldberg, A. Binder, AM Rubinstein, E. Hermano, M. Elkin: Heparanase in inflammation and inflammation-associated cancer. In: The FEBS journal. Volume 280, Number 10, May 2013, pp. 2307-2319, ISSN 1742-4658 . doi : 10.1111 / febs.12184 . PMID 23398975 . PMC 3651782 (free full text).