heparanase (heparanase-1; Hpa1; endo-glucoronidase; P1-A-1 platelet antigen [Contains: Heparanase 8 kD subunit; Heparanase 50 kD subunit], HPSE, HEP, HPA, HPA1, HPR1, HPSE1, HSE1)
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Function
- endoglycosidase, cell surface & extracellular matrix- degrading enzyme
- cleaves heparan sulfate proteoglycans into heparan sulfate side chains & core proteoglycans
- role in extravasation of leukocytes
- role in angiogenesis
Cofactor: activated by Ca+2 & Mg+2
Inhibition:
- Optimum pH is 4-6
Structure
- active heterodimer is composed of the 8 and 50 kD subunits, proteolytic products
- proteolytically processed; cleavage of 65 kD form generate linker peptide, 8 kD & 50 kD peptides
- active form, 8/50 kD heterodimer, is resistant to degradation
- complete removal of linker peptide required for complete activation of enzyme
- N-glycosylated
- glycosylation of the 50 kD subunit essential for solubility
- belongs to the glycosyl hydrolase 79 family
Compartment
- lysosomal membrane; peripheral membrane, secreted
- secreted, internalised & transferred to late endosomes/ lysosomes as proheparanase
- in lysosomes, processed into active form, heparanase
- uptake or internalisation of proheparanase is mediated by heparan sulfate proteoglycans
- heparin inhibits internalization
Expression
- expressed in placenta, spleen > lymph node, thymus, peripheral blood leukocytes, bone marrow, endothelial cells, fetal liver
Pathology
- role in extravasation of tumor cells
- role in metastasis & angiogenesis
- weakly expressed in tumor cells