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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)
Function:
1) endoglycosidase, cell surface & extracellular matrix- degrading enzyme
2) cleaves heparan sulfate proteoglycans into heparan sulfate side chains & core proteoglycans
3) role in extravasation of leukocytes
4) role in angiogenesis
Cofactor: activated by Ca+2 & Mg+2
Inhibition:
- inhibited by EDTA, laminarin sulfate and, to a lesser extent, by heparin & sulfamin
Kinetic parameters:
- 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
Related
heparanase-2 (Hpa2, HPSE2, HPA2)
HPA-1a type in blood
General
glycosidase (glycoside hydrolase)
membrane protein
secreted protein
Properties
SIZE: MW = 61 kD
entity length = 543 aa
COMPARTMENT: lysosome
MOTIF: signal sequence {1-35}
binding site
SITE: 158-162
FOR-BINDING-OF: heparan sulfate
MOTIF: N-glycosylation site {N162}
N-glycosylation site {N178}
N-glycosylation site {N200}
N-glycosylation site {N217}
glutamate residue {E225}
N-glycosylation site {N238}
binding site
SITE: 270-280
FOR-BINDING-OF: heparan sulfate
glutamate residue {E343}
N-glycosylation site {N459}
Database Correlations
OMIM 604724
UniProt Q9Y251
Pfam PF03662
References
UniProt :accession Q9Y251