Hydrolases;
Glycosylases;
Glycosidases, i.e. enzymes that hydrolyse O- and S-glycosyl compounds
BRITE hierarchy

heparan sulfate N-sulfo-D-glucosamine endoglucanase

endohydrolysis of (1->4)-beta-D-glycosidic bonds of heparan sulfate chains in heparan sulfate proteoglycan

(other) R07811(G)
Reaction

Heparanase cleaves the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying either a 3-O-sulfo or a 6-O-sulfo group [2]. Heparanase-1 cuts macromolecular heparin into fragments of 5000--20000 Da [5]. The enzyme cleaves the heparan sulfate glycosaminoglycans from proteoglycan core proteins and degrades them to small oligosaccharides. Inside cells, the enzyme is important for the normal catabolism of heparan sulfate proteoglycans, generating glycosaminoglycan fragments that are then transported to lysosomes and completely degraded. When secreted, heparanase degrades basement membrane heparan sulfate glycosaminoglycans at sites of injury or inflammation, allowing extravasion of immune cells into nonvascular spaces and releasing factors that regulate cell proliferation and angiogenesis [1].

EC 3.2.1.166 created 2010

1  [PMID:11445547]

Bame KJ

Heparanases: endoglycosidases that degrade heparan sulfate proteoglycans.

Glycobiology 11:91R-98R (2001)
DOI:10.1093/glycob/11.6.91R

2  [PMID:20181948]

Peterson SB, Liu J

Unraveling the specificity of heparanase utilizing synthetic substrates.

J Biol Chem 285:14504-13 (2010)
DOI:10.1074/jbc.M110.104166

[hsa:10855]

3  [PMID:9668050]

Pikas DS, Li JP, Vlodavsky I, Lindahl U

Substrate specificity of heparanases from human hepatoma and platelets.

J Biol Chem 273:18770-7 (1998)
DOI:10.1074/jbc.273.30.18770

4  [PMID:12213822]

Okada Y, Yamada S, Toyoshima M, Dong J, Nakajima M, Sugahara K

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.

J Biol Chem 277:42488-95 (2002)
DOI:10.1074/jbc.M206510200

[hsa:10855]

5  [PMID:17635638]

Vreys V, David G

Mammalian heparanase: what is the message?

J Cell Mol Med 11:427-52 (2007)
DOI:10.1111/j.1582-4934.2007.00039.x

6  [PMID:12837765]

Gong F, Jemth P, Escobar Galvis ML, Vlodavsky I, Horner A, Lindahl U, Li JP

Processing of macromolecular heparin by heparanase.

J Biol Chem 278:35152-8 (2003)
DOI:10.1074/jbc.M300925200

[mmu:15442]

7  [PMID:10446189]

Toyoshima M, Nakajima M

Human heparanase. Purification, characterization, cloning, and expression.

J Biol Chem 274:24153-60 (1999)
DOI:10.1074/jbc.274.34.24153

[hsa:10855]

8  [PMID:12460766]

Miao HQ, Navarro E, Patel S, Sargent D, Koo H, Wan H, Plata A, Zhou Q, Ludwig D, Bohlen P, Kussie P

Cloning, expression, and purification of mouse heparanase.

Protein Expr Purif 26:425-31 (2002)
DOI:10.1016/S1046-5928(02)00558-2

[mmu:15442]

9  [PMID:19748475]

Hammond E, Li CP, Ferro V

Development of a colorimetric assay for heparanase activity suitable for kinetic  analysis and inhibitor screening.

Anal Biochem 396:112-6 (2010)
DOI:10.1016/j.ab.2009.09.007