Reactome | Heparanase (HPSE) cleaves heparan sulfate from its proteoglycan (lysosome)

Heparanase (HPSE) cleaves heparan sulfate from its proteoglycan (lysosome)

Stable Identifier

R-HSA-1667005

Type

Reaction [transition]

Species

Homo sapiens

Compartment

lysosomal lumen

ReviewStatus

5/5

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Heparanase (HPSE) cleaves heparan sulfate from its proteoglycan (lysosome)

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Heparanase (HPSE) is an endoglycosidase that cleaves heparan sulfate (HS) chains from its HS proteoglycan (HSPG), by selectively cleaving the linkage between a glucuronic acid (GlcA) unit and an N-sulfo glucosamine unit (GlcNACS, Toyoshima & Nakajima 1999; Okada et al. 2002). We show the cleavage of the -GlcNAcS-GlcA- bond nearest to the protein, leaving the tetrasaccharide GlcA-Gal-Gal-Xyl linker attached to the core protein. The formation of a heterodimer of 8kDa and 50kDa subunits cleaved from the 65kDa form is required for enzyme activity (Levy-Adam et al. 2003) and this proteolytic cleavage occurs in the lysosome (Goldshmidt et al. 2002). Acidic conditions within the lysosome optimises HPSE activity.

Literature References

PubMed ID	Title	Journal	Year
12213822	Structural recognition by recombinant human heparanase that plays critical roles in tumor metastasis. Hierarchical sulfate groups with different effects and the essential target disulfated trisaccharide sequence Okada, Y, Yamada, S, Toyoshima, M, Dong, J, Nakajima, M, Sugahara, K	J Biol Chem	2002
12927802	Heterodimer formation is essential for heparanase enzymatic activity Levy-Adam, F, Miao, HQ, Heinrikson, RL, Vlodavsky, I, Ilan, N	Biochem Biophys Res Commun	2003
12441129	Human heparanase is localized within lysosomes in a stable form Goldshmidt, O, Nadav, L, Aingorn, H, Irit, C, Feinstein, N, Ilan, N, Zamir, E, Geiger, B, Vlodavsky, I, Katz, BZ	Exp Cell Res	2002
10446189	Human heparanase. Purification, characterization, cloning, and expression Toyoshima, M, Nakajima, M	J Biol Chem	1999