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Information on EC 3.2.1.166 - heparanase and Organism(s) Homo sapiens

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EC Tree
     3 Hydrolases
         3.2 Glycosylases
             3.2.1 Glycosidases, i.e. enzymes that hydrolyse O- and S-glycosyl compounds
                3.2.1.166 heparanase
IUBMB Comments
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 . Heparanase-1 cuts macromolecular heparin into fragments of 5000--20000 Da . 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 .
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Homo sapiens
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
endohydrolysis of (1->4)-beta-D-glycosidic bonds of heparan sulfate chains in heparan sulfate proteoglycan
Synonyms
heparanase, heparanase-1, endo-beta-d-glucuronidase, endo-beta-glucuronidase, heparanase 1, c1a heparanase, bphep, heparan sulfate glycosidase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
endo-beta-D-glucuronidase
-
endo-beta-glucuronidase
-
heparan sulfate glycosidase
-
-
heparanase
-
heparanase 1
-
-
heparanase-1
Hpa1 heparanase
-
T5
-
enzymatically inactive splice variant of human heparanase, in which 144 bp of intron 5 are joined with exon 4
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
endohydrolysis of (1->4)-beta-D-glycosidic bonds of heparan sulfate chains in heparan sulfate proteoglycan
show the reaction diagram
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
heparan sulfate N-sulfo-D-glucosamine endoglucanase
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].
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid 2-sulfate-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-GlcUA-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-GlcUA-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate + H2O
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid 2-sulfate-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-GlcUA-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-GlcUA + GlcN-2-N-sulfate-6-O-sulfate
show the reaction diagram
more than 95% cleavage
-
-
?
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid 2-sulfate-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-IdoUA-(beta-1,4)-GlcNAc-6-O-sulfate-(alpha-1,4)-GlcUA-(beta-1,4)-GlcN-2-N-sulfate-3-O-sulfate-6-O-sulfate + H2O
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid 2-sulfate-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-IdoUA-(beta-1,4)-GlcNAc-6-O-sulfate-(alpha-1,4)-GlcUA + GlcN-2-N-sulfate-3-O-sulfate-6-O-sulfate
show the reaction diagram
26% cleavage
-
-
?
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid 2-sulfate-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-IdoUA-(beta-1,4)-GlcNAc-6-O-sulfate-(alpha-1,4)-GlcUA-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate + H2O
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid 2-sulfate-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-IdoUA-(beta-1,4)-GlcNAc-6-O-sulfate-(alpha-1,4)-GlcUA + GlcN-2-N-sulfate-6-O-sulfate
show the reaction diagram
85% cleavage
-
-
?
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-GlcUA-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate + H2O
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-GlcUA + GlcN-2-N-sulfate-6-O-sulfate
show the reaction diagram
40% cleavage
-
-
?
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-GlcUA-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-GlcUA-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate + H2O
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-GlcUA-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-GlcUA + GlcN-2-N-sulfate-6-O-sulfate
show the reaction diagram
more than 95% cleavage
-
-
?
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid-(beta-1,4)-GlcNAc-6-O-sulfate-(alpha-1,4)-GlcUA-(beta-1,4)-GlcN-2-N-sulfate-3-O-sulfate + H2O
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid-(beta-1,4)-GlcNAc-6-O-sulfate-(alpha-1,4)-GlcUA + GlcN-2-N-sulfate-3-O-sulfate
show the reaction diagram
21% cleavage
-
-
?
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid-2-O-sulfate-(beta-1,4)-GlcN-2-N-sulfate-(alpha-1,4)-GlcUA-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate + H2O
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid-2-O-sulfate-(beta-1,4)-GlcN-2-N-sulfate-(alpha-1,4)-GlcUA + GlcN-2-N-sulfate-6-O-sulfate
show the reaction diagram
44% cleavage
-
-
?
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid-2-O-sulfate-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-GlcUA-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate + H2O
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid-2-O-sulfate-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-GlcUA + GlcN-2-N-sulfate-6-O-sulfate
show the reaction diagram
more than 95% cleavage
-
-
?
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid-2-O-sulfate-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-IdoUA-(beta-1,4)-GlcNAc-6-O-sulfate-(alpha-1,4)-GlcUA-(beta-1,4)-GlcN-2-N-sulfate + H2O
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid-2-O-sulfate-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-IdoUA-(beta-1,4)-GlcNAc-6-O-sulfate-(alpha-1,4)-GlcUA + GlcN-2-N-sulfate
show the reaction diagram
59% cleavage
-
-
?
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid-2-O-sulfate-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-IdoUA-(beta-1,4)-GlcNAc-6-O-sulfate-(alpha-1,4)-GlcUA-(beta-1,4)-GlcN-2-N-sulfate-3-O-sulfate + H2O
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid-2-O-sulfate-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-IdoUA-(beta-1,4)-GlcNAc-6-O-sulfate-(alpha-1,4)-GlcUA + GlcN-2-N-sulfate-3-O-sulfate
show the reaction diagram
60% cleavage
-
-
?
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid-2-O-sulfate-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-IdoUA-2-O-sulfate-(beta-1,4)-GlcNAc-(alpha-1,4)-GlcUA-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate + H2O
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid-2-O-sulfate-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-IdoUA-2-O-sulfate-(beta-1,4)-GlcNAc-(alpha-1,4)-GlcUA + GlcN-2-N-sulfate-6-O-sulfate
show the reaction diagram
30% cleavage
-
-
?
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid-2-sulfate-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-GlcUA-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate + H2O
4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid-2-sulfate-(beta-1,4)-GlcN-2-N-sulfate-6-O-sulfate-(alpha-1,4)-GlcUA + GlcN-2-N-sulfate-6-O-sulfate
show the reaction diagram
56% cleavage
-
-
?
extracellular matrix + H2O
?
show the reaction diagram
-
-
-
-
?
fondaparinux + H2O
2N-sulfo-6-O-sulfo-alpha-D-GlcN-(1->4)-beta-GlcA + a trisaccharide
show the reaction diagram
fondaparinux + H2O
?
show the reaction diagram
-
-
-
-
?
heparan sulfate + H2O
?
show the reaction diagram
heparan sulfate + H2O
heparan sulfate fragment + truncated heparan sulfate proteoglycan
show the reaction diagram
catalytic mechanism that involves two conserved acidic residues, a putative proton donor at Glu225 and a nucleophile at Glu343
-
-
?
heparan sulfate proteoglycan + H2O
?
show the reaction diagram
-
-
-
-
?
heparan sulfate proteoglycan + H2O
heparan sulfate fragment + truncated heparan sulfate proteoglycan
show the reaction diagram
heparan sulphate proteoglycan + H2O
heparan sulfate fragment + truncated heparan sulfate proteoglycan
show the reaction diagram
-
-
-
?
heparansulfate proteoglycan + H2O
?
show the reaction diagram
-
-
-
?
heparin + H2O
?
show the reaction diagram
heparin octasaccharide + H2O
?
show the reaction diagram
cleavage of the single beta-D-glucuronidic linkage in a heparin-derived octasaccharide with high affinity for antithrombin
-
-
?
heparin sulfate + H2O
?
show the reaction diagram
cleavage to 5000 Da oligosaccharides
-
-
?
insulin-like growth factor 2 receptor + H2O
?
show the reaction diagram
-
-
-
?
low density receptor-related protein-1 + H2O
?
show the reaction diagram
-
-
-
?
methyl 2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranosyl-(1,4)-beta-D-glucopyranuronosyl-(1,4)-2-deoxy-3,6-di-O-sulfo-2-(sulfoamino)-D-glucopyranosyl-(1,4)-2-O-sulfo-alpha-L-idopyranuronosyl-(1,4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranoside + H2O
4-O-[2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranosyl]-D-glucopyranuronic acid + methyl 2-deoxy-3,6-di-O-sulfo-2-(sulfoamino)-D-glucopyranosyl-(1,4)-2-O-sulfo-alpha-L-idopyranuronosyl-(1,4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranoside
show the reaction diagram
i.e. fondaparinux
-
-
?
sulfated PG545 + H2O
?
show the reaction diagram
-
-
-
-
?
sulfated trisaccharide from PG545 + H2O
?
show the reaction diagram
-
-
-
-
?
syndecan-1 + H2O
?
show the reaction diagram
[GlcAbeta(1,4)GlcNSO3H-3SO3Halpha(1,4)]m-GlcAbeta(1,4)GlcNSO3H-3SO3Halpha(1,4)-[GlcAbeta(1,4)GlcNSO3H-3SO3H]n + H2O
[GlcAbeta(1,4)GlcNSO3H-3SO3Halpha(1,4)]m-GlcA + GlcNSO3H-3SO3Halpha(1,4)-[GlcAbeta(1,4)GlcNSO3H-3SO3H]n
show the reaction diagram
both N- and O-sulfations (either 6-O-sulfation or 3-O-sulfation) are required for the cleavage by heparanase. Structural moiety recognized by heparanase includes a GlcA unit and GlcNS unit carrying O-sulfations. The enzyme proves to be promiscuous in the aspect of the type and location of O-sulfation required for recognition
-
-
?
[GlcAbeta(1,4)GlcNSO3H-6SO3Halpha(1,4)]m-GlcAbeta(1,4)GlcNSO3H-6SO3Halpha(1,4)-[GlcAbeta(1,4)GlcNSO3H-6SO3H]n + H2O
[GlcAbeta(1,4)GlcNSO3H-6SO3Halpha(1,4)]m-GlcA + GlcNSO3H-6SO3Halpha(1,4)-[GlcAbeta(1,4)GlcNSO3H-3SO3H]n
show the reaction diagram
both N- and O-sulfations (either 6-O-sulfation or 3-O-sulfation) are required for the cleavage by heparanase. Structural moiety recognized by heparanase includes a GlcA unit and GlcNS unit carrying O-sulfations. The enzyme proves to be promiscuous in the aspect of the type and location of O-sulfation required for recognition
-
-
?
[GlcAbeta(1,4)GlcNSO3Halpha(1,4)]m-GlcAbeta(1,4)GlcNSO3Halpha(1,4)-[GlcAbeta(1,4)GlcNSO3H]n + H2O
[GlcAbeta(1,4)-GlcNSO3Halpha(1,4)]m-GlcA + GlcNSO3Halpha(1,4)-[GlcAbeta(1,4)GlcNSO3H]n
show the reaction diagram
heparanase does not cleave the linkage of GlcA2S-GlcNS but rather cleaves the linkage of GlcA-GlcNS nearby
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
heparan sulfate + H2O
?
show the reaction diagram
heparan sulfate proteoglycan + H2O
heparan sulfate fragment + truncated heparan sulfate proteoglycan
show the reaction diagram
syndecan-1 + H2O
?
show the reaction diagram
-
heparanase promotes the activity of this mitogenic protein by removing the heparan sulfate chains from syndecan-1 leaving the deglycanated heparan sulfate proteoglycans as the active receptor for lacritin
-
-
?
additional information
?
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis-(1H-benzo[d]imidazole-2,5-diyl))bis(acetyl))bis(azanediyl))bis-(methylene))diboronic acid
-
(((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis-(benzo[d]oxazole-2,5-diyl))bis(acetyl))bis(azanediyl))bis(3-methylbutane-1,1-diyl))diboronic acid
-
(((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis-(benzo[d]oxazole-2,5-diyl))bis(acetyl))bis(azanediyl))bis-(methylene))diboronic acid
-
(2E)-N-(3,4-dichlorophenyl)-3-[3-fluoro-4-[5-(2-oxopropyl)-1,3-benzoxazol-2-yl]phenyl]prop-2-enamide
-
-
(3R,5S)-8-nonyl-9-oxo-1,6-dioxaspiro[4.4]non-7-ene-2,2,3-tricarboxylic acid
-
-
(3S,4S,5R,6R)-4,5-dihydroxy-6-[(trifluoroacetyl)amino]piperidine-3-carboxylic acid
-
-
(3S,4S,5R,6R)-6-(acetylamino)-4,5-dihydroxypiperidine-3-carboxylic acid
-
-
(5R)-3-heptadecanoyl-5-(hydroxymethyl)-4-methoxyfuran-2(5H)-one
-
-
(5R)-4-(benzyloxy)-3-heptadecanoyl-5-(hydroxymethyl)furan-2(5H)-one
-
-
(5S)-8-nonyl-9-oxo-1,6-dioxaspiro[4.4]non-7-ene-2,2,3-tricarboxylic acid
-
-
(IdoA2S-GlcNS)n
polysaccharide containing IdoA2S-GlcNS repeating unit, inhibits the activity of heparanase
1,3-bis(1-(5,6-dimethylbenzo[d]oxazol-2-yl)piperidin-4-yl)urea
-
1,3-bis(4-(5,6-dimethylbenzo[d]oxazol-2-yl)-2-fluorophenyl)urea
-
1,3-bis(4-(5,6-dimethylbenzo[d]oxazol-2-yl)phenyl)urea
-
1,3-bis[4-(1H-benzimidazol-2-yl)phenyl]urea
-
-
1,3-bis[4-(5,6-dimethyl-1H-benzimidazol-2-yl)phenyl]urea
1-[2-([3-[(7-chloroquinolin-4-yl)amino]-5-(hydroxymethyl)benzyl]amino)prop-2-en-1-yl]piperidin-4-ol
-
-
1-[3-[(7-chloroquinolin-4-yl)amino]-5-([[3-(piperidin-1-yl)prop-1-en-2-yl]amino]methyl)benzyl]piperidin-4-ol
-
-
2,2'-((((carbonylbis(azanediyl))bis(4,1-phenylenesulfonyl))bis-(azanediyl))bis(3,1-phenylene))diacetic acid
-
2,2'-((((Iminomethylene)bis(azanediyl))bis(4,1-phenylene))bis-(benzo[d]oxazole-2,5-diyl))diacetic acid
-
2,2'-(((4,4'-(2-hydroxypropane-1,3-diyl)bis(benzoyl))bis-(azanediyl))bis(3,1-phenylene))diacetic acid
-
2,2'-(((4,4'-(2-oxopropane-1,3-diyl)bis(benzoyl))bis-(azanediyl))bis(3,1-phenylene))diacetic acid
-
2,2'-(((4,4'-(carbonylbis(azanediyl))bis(benzoyl))bis(azanediyl))-bis(3,1-phenylene))diacetic acid
-
2,2'-(((4,4'-(carbonylbis(azanediyl))bis(benzoyl))bis(azanediyl))-bis(4-hydroxy-3,1-phenylene))diacetic acid
-
2,2'-(((4,4'-(thiocarbonylbis(azanediyl))bis(3-fluorobenzoyl))bis-(azanediyl))bis(3,1-phenylene))diacetic acid
-
2,2'-(((carbonylbis(azanediyl))bis(3,1-phenylene))bis(benzo[d]-oxazole-2,5-diyl))diacetic acid
-
2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis-(1H-benzo[d]imidazole-2,5-diyl))diacetic acid
-
2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis-(benzo[d]oxazole-2,5-diyl))bis(N-isopentylacetamide)
-
2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis-(benzo[d]oxazole-2,5-diyl))diacetic acid
causes inhibition of the proliferation of human CME-1 synovial sarcoma cells
2,2'-(((carbonylbis(azanediyl))bis(4,1-phenylene))bis(benzo[d]-oxazole-2,5-diyl))diacetic acid
-
2,2'-(((carbonylbis(azanediyl))bis(piperidine-4,1-diyl))bis(benzo-[d]oxazole-2,5-diyl))diacetic acid
-
2,2'-(((thiocarbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))-bis(1H-benzo[d]imidazole-2,5-diyl))diacetic acid
-
2,2'-(((thiocarbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))-bis(benzo[d]oxazole-2,5-diyl))diacetic acid
-
2,2'-(((thiocarbonylbis(azanediyl))bis(4,1-phenylene))bis(benzo-[d]oxazole-2,5-diyl))diacetic acid
-
2,2'-((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis(1H-benzo[d]imidazole-2,5-diyl))bis(acetyl))bis-(azanediyl))bis(3-phenylpropanoic acid)
-
2,2'-((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis(benzo[d]oxazole-2,5-diyl))bis(acetyl))bis-(azanediyl))bis(3-phenylpropanoic acid)
-
2,2'-((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis(benzo[d]oxazole-2,5-diyl))bis(acetyl))bis-(azanediyl))diacetic acid
-
2,2'-((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis(benzo[d]oxazole-2,5-diyl))bis(acetyl))bis-(azanediyl))dipropionic acid
-
2,2'-((2,2'-(((thiocarbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis(benzo[d]oxazole-2,5-diyl))bis(acetyl))bis-(azanediyl))diacetic acid
-
2-(3-(4-(3-(4-((5-(carboxymethyl)-2-hydroxyphenyl)carbamoyl)-phenyl)-2-hydroxypropyl)-3-hydroxybenzamido)phenyl)acetic acid
-
2-[(3-[4-[3-(4-chloro-2-cyclohexylphenoxy)-5-nitrophenoxy]phenyl]propanoyl)amino]ethanesulfonic acid
-
-
2-[2-methoxy-5-(5-phenyl-1,3-benzoxazol-2-yl)-4-(propylamino)phenyl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylic acid
-
-
2-[3-(1,3-benzoxazol-2-yl)phenyl]-1,3-dioxo-2,3-dihydro-1H-indene-5-carboxylic acid
-
-
2-[3-[5-(4-chlorophenyl)-1,3-benzoxazol-2-yl]-4-(propylamino)phenyl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylic acid
-
-
2-[3-[5-(4-fluorophenyl)-1,3-benzoxazol-2-yl]-4-(propylamino)phenyl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylic acid
-
-
2-[4-[4-(6-amino-1H-benzimidazol-2-yl)phenoxy]phenyl]-1H-benzimidazol-5-amine
-
-
3,3'-((4,4'-(carbonylbis(azanediyl))bis(benzoyl))bis(azanediyl))-dibenzoic acid
-
3-heptadecanoyl-4-hydroxy-5-(hydroxymethyl)furan-2(5H)-one
-
-
3-[(7-chloroquinolin-4-yl)amino]-N-[2-(dimethylamino)ethyl]-5-([[3-(piperidin-1-yl)prop-1-en-2-yl]amino]methyl)benzamide
-
-
3-[(7-chloroquinolin-4-yl)amino]-N-[2-(morpholin-4-yl)ethyl]-5-([[3-(piperidin-1-yl)prop-1-en-2-yl]amino]methyl)benzamide
-
-
4-[(4-carboxy-3-hydroxy-5-methylphenoxy)carbonyl]-3-hydroxy-5-pentadecylphenyl beta-D-glucopyranosiduronic acid
-
-
4-[(4-carboxy-3-hydroxy-5-methylphenoxy)carbonyl]-3-hydroxy-5-pentadecylphenyl methyl beta-D-glucopyranosiduronate
-
-
4-[(7-chloroquinolin-4-yl)amino]-2-(pyrrolidin-1-ylmethyl)phenol
-
-
4-[(7-chloroquinolin-4-yl)amino]phenol
-
-
4-[[5-(3,6-dibromo-9H-fluoren-9-yl)-4-hydroxy-2-(2-phenylethyl)pentanethioyl]amino]benzenesulfonic acid
-
-
5-bromo-2-hydroxy-N-[(E)-(3-[2-[(4-methylphenyl)amino]-2-oxoethyl]-2-oxo-2,3-dihydro-1H-inden-1-ylidene)methyl]benzamide
-
-
5-[2-[4-([4-[(3-bromo-4-methoxybenzoyl)amino]benzyl]amino)-3-fluorophenyl]-1H-benzimidazol-5-yl]-4-oxopentanoic acid
i.e. SST0871AA1
5-[3-(2-methylidenenonadecyl)-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]-2-phenoxybenzenesulfonic acid
-
-
7-chloro-N-[3-([[3-(piperidin-1-yl)prop-1-en-2-yl]amino]methyl)-5-([[3-(piperidin-1-yl)prop-1-en-2-yl]oxy]methyl)phenyl]quinolin-4-amine
-
-
7-chloro-N-[3-[(diethylamino)methyl]-4-(morpholin-4-yl)phenyl]quinolin-4-amine
-
-
7-chloro-N-[4-(furan-2-yl)-3-(pyrrolidin-1-ylmethyl)phenyl]quinolin-4-amine
-
-
7-chloro-N-[4-ethoxy-3-(pyrrolidin-1-ylmethyl)phenyl]quinolin-4-amine
-
-
amodiaquine
-
an antimalarial drug
astemizole
-
-
cisapride
-
-
defibrotide
a polydisperse oligonucleotide isolated from porcine mucosa that has multiple biological effects including inhibition of heparanase gene expression and enzymatic activity
-
heparanase inhibitor PI-88
a mixture of highly sulfated, monophosphorylated mannose oligosaccharides, derived from the extracellular phosphomannan of the yeast Pichia holstii, with potential antiangiogenic activity
-
heparin
hesperidin
-
-
labetalol
-
-
low molecular weight heparin
-
-
-
Lys-Lys-Asp-Cys
0.025 mM or above
M402
-
a glycol-split heparin compound similar to SST0001 yet smaller in molecular mass
maltohexaose sulfate
with at least 3 sulfate groups per internal sugar and up to four sulfates in the terminal sugar residues, docking sstudy and binding structure, overview
metergoline
-
-
muparfostat
formally PI-88, a phosphomannopentaose
N'-[3-[(7-chloroquinolin-4-yl)amino]-5-([[3-(piperidin-1-yl)prop-1-en-2-yl]amino]methyl)benzyl]-N,N-dimethylethane-1,2-diamine
-
-
N-[4-([[4-(1H-benzimidazol-2-yl)phenyl]amino]methyl)phenyl]-3-bromo-4-methoxybenzamide
-
-
N-[4-([[5-(1H-benzimidazol-2-yl)pyridin-2-yl]amino]methyl)phenyl]-3-bromo-4-methoxybenzamide
-
-
N-[4-bromo-3-[(diethylamino)methyl]phenyl]-7-chloroquinolin-4-amine
-
-
naringin
-
-
necuparanib
formally M402, an N-sulfated glycol-split heparin of 6 kDa, shows efficacy in metastasis models
-
oligomannurarate sulfate
the heparanase inhibitor simultaneously targets basic fibroblast growth factor, combats tumor angiogenesis and metastasis. The inhibitor is a promising candidate agent for cancer therapy
-
oligomannurarate sulphate
-
oligomanurarate sulfate
-
JG3, a marine-derived oligosaccharide and a heparanase inhibitor
PG545
PG545 cholestanol aglycon
-
the cholestanol aglycon of PG545 significantly increased affinity for heparanase and also modified the inhibition mode, parabolic competition
PG545 trisaccharide derivative
-
-
PI-88
roneparstat
sodium octyl 2-deoxy-2-(sulfonatoamino)-alpha-D-glucopyranoside
-
-
sodium octyl 4-O-[2-deoxy-2-(sulfoamino)-alpha-D-glucopyranosyl]-beta-D-glucopyranosiduronate
-
specific inhibition
sodium octyl beta-D-glucopyranosiduronate
-
-
SST0001
sulfated PG545
-
competitive inhibition
sulfated trisaccharide from PG545
-
partial competitive inhibition
sulodexide
-
-
[2-(2-carboxybenzoyl)-6-(phenylsulfanyl)phenyl](hydroxy)oxoammonium
-
-
[2-(4-[[(2E)-3-(4-bromophenyl)prop-2-enoyl]amino]phenyl)-1,3-benzoxazol-5-yl]acetic acid
-
[2-[4-([4-[(3-bromo-4-methoxybenzoyl)amino]benzyl]amino)-3-fluorophenyl]-1H-benzimidazol-5-yl]acetic acid
i.e. SST0867AA1
[3-[(7-chloroquinolin-4-yl)amino]-5-([[3-(morpholin-4-yl)prop-1-en-2-yl]amino]methyl)phenyl]methanol
-
-
[3-[(7-chloroquinolin-4-yl)amino]-5-([[3-(piperidin-1-yl)prop-1-en-2-yl]amino]methyl)phenyl](morpholin-4-yl)methanone
-
-
[4-(5-[2-chloro-4-[(4-chlorobenzoyl)amino]phenyl]furan-2-yl)-1,3-thiazol-2-yl]acetic acid
-
-
[4-[5-(2,4-dichlorophenyl)furan-2-yl]-1,3-oxazol-2-yl]acetic acid
-
-
[4-[5-(4-[[(2E)-3-(4-bromophenyl)prop-2-enoyl]amino]-2-chlorophenyl)furan-2-yl]-1,3-thiazol-2-yl]acetic acid
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
angiotensin II
-
-
histidine-rich glycoprotein
GeneBank accession number: BAA21613. Directly interacts with platelet-derived heparanase and enhances its enzymatic activity
-
oxidized LDL
-
-
-
palmitic acid
-
palmitic acid-induced nuclear entry of heparanase facilitates heparan sulfate cleavage
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0036
fondaparinux
-
pH 5.0, 37°C
0.046
methyl 2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranosyl-(1,4)-beta-D-glucopyranuronosyl-(1,4)-2-deoxy-3,6-di-O-sulfo-2-(sulfoamino)-D-glucopyranosyl-(1,4)-2-O-sulfo-alpha-L-idopyranuronosyl-(1,4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranoside
pH 5.0, 37°C, i.e. fondaparinux
0.0124
sulfated PG545
-
pH 5.0, 37°C
0.197
sulfated trisaccharide from PG545
-
pH 5.0, 37°C
additional information
additional information
-
Michaelis-Menten kinetics
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3.5
methyl 2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranosyl-(1,4)-beta-D-glucopyranuronosyl-(1,4)-2-deoxy-3,6-di-O-sulfo-2-(sulfoamino)-D-glucopyranosyl-(1,4)-2-O-sulfo-alpha-L-idopyranuronosyl-(1,4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranoside
pH 5.0, 37°C, i.e. fondaparinux
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0000079
heparanase inhibitor PI-88
pH 5.0, 37°C
-
0.000006 - 0.00444
PG545
additional information
additional information
PG517: 162 nM, PG518: 59 nM, PG536: 6 nM, PG537: 6 nM, PG545: 6 nM, PG546: 4 nM, PG547: 16 nM, PG554: 9 nM, PG561: 11 nM, PG562: 9 nM, PI-88: 8 nM
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.01
(((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis-(1H-benzo[d]imidazole-2,5-diyl))bis(acetyl))bis(azanediyl))bis-(methylene))diboronic acid
Homo sapiens
above, pH 5.0 37°C, recombinant enzyme
0.00487 - 0.01
(((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis-(benzo[d]oxazole-2,5-diyl))bis(acetyl))bis(azanediyl))bis(3-methylbutane-1,1-diyl))diboronic acid
0.00001
(((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis-(benzo[d]oxazole-2,5-diyl))bis(acetyl))bis(azanediyl))bis-(methylene))diboronic acid
Homo sapiens
pH 5.0 37°C, recombinant enzyme
0.01
1,3-bis(1-(5,6-dimethylbenzo[d]oxazol-2-yl)piperidin-4-yl)urea
Homo sapiens
above, pH 5.0 37°C, recombinant enzyme
0.01
1,3-bis(4-(5,6-dimethylbenzo[d]oxazol-2-yl)-2-fluorophenyl)urea
Homo sapiens
above, pH 5.0 37°C, recombinant enzyme
0.01
1,3-bis(4-(5,6-dimethylbenzo[d]oxazol-2-yl)phenyl)urea
Homo sapiens
above, pH 5.0 37°C, recombinant enzyme
0.00056
1,3-bis[4-(5,6-dimethyl-1H-benzimidazol-2-yl)phenyl]urea
Homo sapiens
pH 5.0 37°C, recombinant enzyme
0.01
2,2'-((((carbonylbis(azanediyl))bis(4,1-phenylenesulfonyl))bis-(azanediyl))bis(3,1-phenylene))diacetic acid
Homo sapiens
above, pH 5.0 37°C, recombinant enzyme
0.00602
2,2'-((((Iminomethylene)bis(azanediyl))bis(4,1-phenylene))bis-(benzo[d]oxazole-2,5-diyl))diacetic acid
Homo sapiens
pH 5.0 37°C, recombinant enzyme
0.01
2,2'-(((4,4'-(2-hydroxypropane-1,3-diyl)bis(benzoyl))bis-(azanediyl))bis(3,1-phenylene))diacetic acid
Homo sapiens
above, pH 5.0 37°C, recombinant enzyme
0.01
2,2'-(((4,4'-(2-oxopropane-1,3-diyl)bis(benzoyl))bis-(azanediyl))bis(3,1-phenylene))diacetic acid
Homo sapiens
above, pH 5.0 37°C, recombinant enzyme
0.00176
2,2'-(((4,4'-(carbonylbis(azanediyl))bis(benzoyl))bis(azanediyl))-bis(3,1-phenylene))diacetic acid
Homo sapiens
pH 5.0 37°C, recombinant enzyme
0.00273
2,2'-(((4,4'-(carbonylbis(azanediyl))bis(benzoyl))bis(azanediyl))-bis(4-hydroxy-3,1-phenylene))diacetic acid
Homo sapiens
pH 5.0 37°C, recombinant enzyme
0.00261
2,2'-(((4,4'-(thiocarbonylbis(azanediyl))bis(3-fluorobenzoyl))bis-(azanediyl))bis(3,1-phenylene))diacetic acid
Homo sapiens
pH 5.0 37°C, recombinant enzyme
0.01
2,2'-(((carbonylbis(azanediyl))bis(3,1-phenylene))bis(benzo[d]-oxazole-2,5-diyl))diacetic acid
Homo sapiens
above, pH 5.0 37°C, recombinant enzyme
0.00098
2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis-(1H-benzo[d]imidazole-2,5-diyl))diacetic acid
Homo sapiens
pH 5.0 37°C, recombinant enzyme
0.01
2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis-(benzo[d]oxazole-2,5-diyl))bis(N-isopentylacetamide)
Homo sapiens
above, pH 5.0 37°C, recombinant enzyme
0.00018
2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis-(benzo[d]oxazole-2,5-diyl))diacetic acid
Homo sapiens
pH 5.0 37°C, recombinant enzyme
0.0032
2,2'-(((carbonylbis(azanediyl))bis(4,1-phenylene))bis(benzo[d]-oxazole-2,5-diyl))diacetic acid
Homo sapiens
pH 5.0 37°C, recombinant enzyme
0.01
2,2'-(((carbonylbis(azanediyl))bis(piperidine-4,1-diyl))bis(benzo-[d]oxazole-2,5-diyl))diacetic acid
Homo sapiens
above, pH 5.0 37°C, recombinant enzyme
0.00099
2,2'-(((thiocarbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))-bis(1H-benzo[d]imidazole-2,5-diyl))diacetic acid
Homo sapiens
pH 5.0 37°C, recombinant enzyme
0.0014
2,2'-(((thiocarbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))-bis(benzo[d]oxazole-2,5-diyl))diacetic acid
Homo sapiens
pH 5.0 37°C, recombinant enzyme
0.00181
2,2'-(((thiocarbonylbis(azanediyl))bis(4,1-phenylene))bis(benzo-[d]oxazole-2,5-diyl))diacetic acid
Homo sapiens
pH 5.0 37°C, recombinant enzyme
0.00082 - 0.01
2,2'-((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis(1H-benzo[d]imidazole-2,5-diyl))bis(acetyl))bis-(azanediyl))bis(3-phenylpropanoic acid)
0.00072
2,2'-((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis(benzo[d]oxazole-2,5-diyl))bis(acetyl))bis-(azanediyl))bis(3-phenylpropanoic acid)
Homo sapiens
pH 5.0 37°C, recombinant enzyme
0.00045
2,2'-((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis(benzo[d]oxazole-2,5-diyl))bis(acetyl))bis-(azanediyl))diacetic acid
Homo sapiens
pH 5.0 37°C, recombinant enzyme
0.00037
2,2'-((2,2'-(((carbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis(benzo[d]oxazole-2,5-diyl))bis(acetyl))bis-(azanediyl))dipropionic acid
Homo sapiens
pH 5.0 37°C, recombinant enzyme
0.00008
2,2'-((2,2'-(((thiocarbonylbis(azanediyl))bis(3-fluoro-4,1-phenylene))bis(benzo[d]oxazole-2,5-diyl))bis(acetyl))bis-(azanediyl))diacetic acid
Homo sapiens
pH 5.0 37°C, recombinant enzyme
0.01
2-(3-(4-(3-(4-((5-(carboxymethyl)-2-hydroxyphenyl)carbamoyl)-phenyl)-2-hydroxypropyl)-3-hydroxybenzamido)phenyl)acetic acid
Homo sapiens
above, pH 5.0 37°C, recombinant enzyme
0.00917
3,3'-((4,4'-(carbonylbis(azanediyl))bis(benzoyl))bis(azanediyl))-dibenzoic acid
Homo sapiens
pH 5.0 37°C, recombinant enzyme
0.00064
5-[2-[4-([4-[(3-bromo-4-methoxybenzoyl)amino]benzyl]amino)-3-fluorophenyl]-1H-benzimidazol-5-yl]-4-oxopentanoic acid
Homo sapiens
pH 5.0 37°C, recombinant enzyme
0.000025
heparanase inhibitor PI-88
Homo sapiens
pH 5.0, 37°C
-
0.00002
heparin
Homo sapiens
heparanase action toward antithrombin-binding oligosaccharides
0.012
PG545
Homo sapiens
-
pH 5.0, 37°C
0.000003
roneparstat
Homo sapiens
pH and temperature not specified in the publication
6
sodium octyl 2-deoxy-2-(sulfonatoamino)-alpha-D-glucopyranoside
Homo sapiens
-
pH and temperature not specified in the publication
1.4
sodium octyl 4-O-[2-deoxy-2-(sulfoamino)-alpha-D-glucopyranosyl]-beta-D-glucopyranosiduronate
Homo sapiens
-
pH and temperature not specified in the publication
0.000005
SST0001
Homo sapiens
pH 5.0 37°C, recombinant enzyme
0.416
sulfated PG545
Homo sapiens
-
pH 5.0, 37°C
4.82
sulfated trisaccharide from PG545
Homo sapiens
-
pH 5.0, 37°C
0.00042
[2-(4-[[(2E)-3-(4-bromophenyl)prop-2-enoyl]amino]phenyl)-1,3-benzoxazol-5-yl]acetic acid
Homo sapiens
pH 5.0 37°C, recombinant enzyme
0.00286
[2-[4-([4-[(3-bromo-4-methoxybenzoyl)amino]benzyl]amino)-3-fluorophenyl]-1H-benzimidazol-5-yl]acetic acid
Homo sapiens
pH 5.0 37°C, recombinant enzyme
additional information
additional information
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
a simple, accurate, and robust biochemical assay for heparanase activity that uses a commercially available homogeneous substrate (fondaparinux) with a single enzymatic cleavage point and, thus, does not have the problems associated with using heparan sulfate-based assays
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 5.8
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
3.5 - 7
no significant activity below pH 3.5 and above pH 7.0
4 - 5.5
pH 4.0: about 80% of maximal activity, pH 5.5: about 60% of maximal activity. pH 7.0: about 20% of maximal activity
4.2 - 6
pH 4.2: maximal activity, pH 6.0: about 50% of maximal activity. No significant activity is observed below pH 3.5 and above pH 7.0
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
9.2
calculated from amino acid sequence
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
heparanase protein is detected primarily within the cytoplasm of the cells, indicating that the enzyme is produced and stored within the cytoplasm of myeloid cells, with limited expression on the cell surface
Manually annotated by BRENDA team
-
overexpression of heparanase in pancreatic adenocarcinomas
Manually annotated by BRENDA team
elevated levels of heparanasen activity are detected in sera and urine samples of patients suffering from diabetic nephropathy or aggressive metastatic disease
Manually annotated by BRENDA team
elevated level of heparanase-activity in bone marrow plasma of myeloma patients
Manually annotated by BRENDA team
-
metastatic breast carcinoma cell lines show a substantial increase in hpa gene expression
Manually annotated by BRENDA team
elevated expression of human heparanase-1 protein occurs in endothelial cells of sprouting capillaries and small vessels in the vicinity of a tumour, but not of mature, quiescent blood vessels
Manually annotated by BRENDA team
heparanase expression is up-regulated in the colon of patients suffering from Crohn's disease and ulcerative colitis
Manually annotated by BRENDA team
purified recombinant detagged enzyme
Manually annotated by BRENDA team
-
heparanase expression in coronary artery disease
Manually annotated by BRENDA team
heparanase-1 mRNA and protein are expressed in the liver and colon of 18-week and 22-week human foetuses, but not in the corresponding mature tissues
Manually annotated by BRENDA team
the enzyme penetrates the endothelial layer that lines blood vessels
Manually annotated by BRENDA team
under normal conditions, heparanase-1 expression is restricted primarily to placental trophoblasts, blood-borne cells and keratinocytes
Manually annotated by BRENDA team
-
heparanase expression in lung cancer samples to understand lung tumor progression and malignancy, overview. Heparanase expression tends to correlate with tumor node metastasis staging in non-small cell lung carcinoma
Manually annotated by BRENDA team
isolated from trabecular bone specimens of patients with osteoporosis and from healthy subjects
Manually annotated by BRENDA team
-
heparanase is preferentially expressed by epidermal keratinocytes in human psoriatic lesions
Manually annotated by BRENDA team
-
plantar stratum corneum
Manually annotated by BRENDA team
heparanase expression is up-regulated in the synovial fluid and tissue of patients suffering from rheumatoid arthritis, but not in unaffected individuals
Manually annotated by BRENDA team
-
heparanase occupies regulatory regions of active genes in T cells
Manually annotated by BRENDA team
elevated level of heparanase-activity is detected in sera and urine samples of patients suffering from diabetic nephropathy or aggressive metastatic disease
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
in blood-borne cells, active heparanase-1 is stored in specific granules, but in response to chemoattractants or inflammatory stimuli it is redistributed to the cell surface and released by degranulation
Manually annotated by BRENDA team
additional information
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
metabolism
-
key enzymes sulfatases and heparanase of the pathway actively influence cancer cell proliferation, signaling, invasion, and metastasis
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
HPSE_HUMAN
543
0
61149
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
15000
-
x * 15000, heparanase splice variant T5, SDS-PAGE
45000
50000
51000
-
x * 51000, active enzyme form, SDS-PAGE
53000
-
1 * 53000 + 1 * 8000, active heterodimeric form, SDS-PAGE
57700
x * 57700, calculated from amino acid sequence
65000
80000
1 * 50000 + 1 * 80000, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
1 * 50000 + 1 * 80000, SDS-PAGE
heterodimer
monomer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
proteolytic modification
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure analyses and homology modelling, overview
purified recombinant heterodimeric wild-type apo-enzyme, X-ray diffraction structure determiantion and analysis at 1.75 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D367A
mutant enzyme is not expressed
Q225A
mutation results in the complete loss of heparanase activity
Q343A
mutation results in the complete loss of heparanase activity
Q378A
mutation does not reduce activity
Q396A
mutation does not reduce activity
additional information
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, loss of 50% activity after storage for 1 year, recombinantly expressed enzyme
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purifiecation of the His-tagged smaller subunit fragment of the human heparanase to homogeneity by immobilized metal affinity chromatography and dialysis from Escherichia coli strain BL21 (DE3)plysS
-
recombinant enzyme from insect cells
recombinant GST-tagged enzyme from Escherichia coli strain BL21 by glutathione affinity chromatography
recombinant His-tagged enzyme from Escherichia coli BL21-DE3 codon plus by metal affinity chromatography
-
recombinant myc-DDK-tagged proheparanase partially by tangential ultrafiltration
recombinant N-terminally His-tagged truncated enzyme form from Escherichia coli strain BL21-CodonPlus (DE3)-RIL by nickel affinity chromatography and dialysis
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Mus musculus
-
expression in CHO cells
expression in COS-7 cells
expression of an N-terminally His-tagged truncated enzyme form, residues 36-543, containing a TEV protease cleavage site, in Escherichia coli strain BL21-CodonPlus (DE3)-RIL
-
expression of the cloned cDNA in insect and mammalian cells yields 65000 Da and 50000 Da recombinant heparanase proteins. The 50000 Da enzyme represents an N-terminally processed enzyme, at least 100fold more active than the 65000 Da form
-
expression of the enzyme in Spodoptera frugiperda Sf9 cells and secretion to the cell culture medium
-
insect cell expression system is used for the generation of large amounts of recombinant protein of high specific activity. Individual subunits are cloned into baculoviral secretory vectors and coexpressed in insect cells
NIH3T3 and COS-7 cells stably transfected with pBK-CMV expression vectors
recombinant expression in insect cells
-
recombinant expression of GST-tagged enzyme from vector pGEX-2TK-heparanase in Escherichia coli strain BL21
recombinant expression of His-tagged smaller 8 kDa subunit in Escherichia coli strain BL21 (DE3)plysS
-
recombinant expression of myc-DDK-tagged proheparanase in HEK-293T cells
recombinant expression of the His-tagged enzyme from pET-15b expression vector containing a TEV cleavage site in Escherichia coli BL21-DE3 codon plus
-
single gene, recombinant expression in Spodoptera frugiperda cells via baculovrius transfection method. The two subunits cotranslationally fold into mature heterodimeric HPSE, bypassing the 65 kDa proenzyme form and ensuring expression of only active enzyme
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
bovine serum albumin and advanced glycation end-product, but not high glucose levels, increase heparanase expression in adult tubular cells via the AKT/PI3K signaling pathway 1.68 and 2.81times, respectively
-
expression is up-regulated as tumors become more aggressive and is associated with enhanced tumor growth, angiogenesis, and metastasis
-
expression of the enzyme heparanase is clearly linked to colon carcinoma progression
-
heparanase expression is enhanced in almost all cancers examined including various carcinomas, sarcomas and hematological malignancies. Upregulation of heparanase expression correlates with increased tumor size, tumor angiogenesis, enhanced metastasis and poor prognosis. Heparanase is upregulated in response to chemotherapy in cancer patients and the surviving cells acquire chemoresistance, attributed, at least in part, to autophagy
heparanase is up-regulated in essentially all human tumors examined. Oxidized lipid- or angiotensin-induced expression of heparanase in macrophages may be a primary mechanism increasing heparanase in atherosclerotic plaques
-
heparanase is upregulated in essentially all human carcinomas
-
heparanase is upregulated in primary human tumors
heparanase variant T5 expression is up-regulated in 75% of human renal cell carcinoma biopsies
-
no effect by TGF-beta on the enzyme expression in enzyme-silenced cells
-
phorbol 12-myristate 13-acetate/calcium iono­mycin stimulation results in a substantial increase in nuclear heparanase in the 53 kDa active form
-
the overall transcriptional activity of the main heparan sulfate biosynthesis-involved genes (EXT1, EXT2, NDST1, NDST2, GLCE, HS2ST1, HS3ST1, HS3ST2, HS6ST1, HS6ST2, SULF1, SULF2, HPSE) is decreased by 1.5-2fold in Grade II-III glioma (p < 0.01) and by 3-fold in Grade IV glioma (glioblastoma multiforme, GBM) (p < 0.05), as compared with the para-tumourous tissue
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
a simple, accurate, and robust biochemical assay for heparanase activity that uses a commercially available homogeneous substrate (fondaparinux) with a single enzymatic cleavage point and, thus, does not have the problems associated with using heparan sulfate-based assays. The assay is suitable for testing heparanase inhibitors and could easily be adapted for use in high-throughput screening applications
diagnostics
upregulation of heparanase expression correlates with increased tumor size, tumor angiogenesis, enhanced metastasis and poor prognosis. Heparanase expressed by tumor cells, innate immune cells, activated endothelial cells as well as other cells of the tumor microenvironment is a master regulator of the aggressive phenotype of cancer and an important contributor to the poor outcome of cancer patients
drug development
medicine
pharmacology
-
targeting enzymes that degrade heparan sulfate proteoglycans highlights one approach to maintain normal tissue architecture, inhibit tumor progression, and block metastasis
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
McKenzie, E.; Young, K.; Hircock, M.; Bennett, J.; Bhaman, M.; Felix, R.; Turner, P.; Stamps, A.; McMillan, D.; Saville, G.; Ng, S.; Mason, S.; Snell, D.; Schofield, D.; Gong, H.; Townsend, R.; Gallagher, J.; Page, M.; Parekh, R.; Stubberfield, C.
Biochemical characterization of the active heterodimer form of human heparanase (Hpa1) protein expressed in insect cells
Biochem. J.
373
423-435
2003
Homo sapiens (Q9Y251), Homo sapiens
Manually annotated by BRENDA team
Hulett, M.D.; Hornby, J.R.; Ohms, S.J.; Zuegg, J.; Freeman, C.; Gready, J.E.; Parish, C.R.
Identification of active-site residues of the pro-metastatic endoglycosidase heparanase
Biochemistry
39
15659-15667
2000
Homo sapiens (Q9Y251), Homo sapiens
Manually annotated by BRENDA team
Zhao, H.; Liu, H.; Chen, Y.; Xin, X.; Li, J.; Hou, Y.; Zhang, Z.; Zhang, X.; Xie, C.; Geng, M.; Ding, J.
Oligomannurarate sulfate, a novel heparanase inhibitor simultaneously targeting basic fibroblast growth factor, combats tumor angiogenesis and metastasis
Cancer Res.
66
8779-8787
2006
Homo sapiens (Q9Y251)
Manually annotated by BRENDA team
Bame, K.J.
Heparanases: endoglycosidases that degrade heparan sulfate proteoglycans
Glycobiology
11
91R-98R
2001
Cricetulus griseus, Homo sapiens (Q9Y251)
Manually annotated by BRENDA team
Dredge, K.; Hammond, E.; Davis, K.; Li, C.P.; Liu, L.; Johnstone, K.; Handley, P.; Wimmer, N.; Gonda, T.J.; Gautam, A.; Ferro, V.; Bytheway, I.
The PG500 series: novel heparan sulfate mimetics as potent angiogenesis and heparanase inhibitors for cancer therapy
Invest. New Drugs
28
276-283
2010
Homo sapiens (Q9Y251)
Manually annotated by BRENDA team
Pikas, D.S.; Li, J.P.; Vlodavsky, I.; Lindahl, U.
Substrate specificity of heparanases from human hepatoma and platelets
J. Biol. Chem.
273
18770-18777
1998
Homo sapiens (Q9Y251), Homo sapiens
Manually annotated by BRENDA team
Toyoshima, M.; Nakajima, M.
Human heparanase. Purification, characterization, cloning, and expression
J. Biol. Chem.
274
24153-24160
1999
Homo sapiens (Q9Y251), Homo sapiens
Manually annotated by BRENDA team
Fairbanks, M.B.; Mildner, A.M.; Leone, J.W.; Cavey, G.S.; Mathews, W.R.; Drong, R.F.; Slightom, J.L.; Bienkowski, M.J.; Smith, C.W.; Bannow, C.A.; Heinrikson, R.L.
Processing of the human heparanase precursor and evidence that the active enzyme is a heterodimer
J. Biol. Chem.
274
29587-29590
1999
Homo sapiens (Q9Y251), Homo sapiens
Manually annotated by BRENDA team
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
42488-42495
2002
Homo sapiens (Q9Y251), Homo sapiens
Manually annotated by BRENDA team
Gong, F.; Jemth, P.; Escobar Galvis, M.L.; Vlodavsky, I.; Horner, A.; Lindahl, U.; Li, J.P.
Processing of macromolecular heparin by heparanase
J. Biol. Chem.
278
35152-35158
2003
Homo sapiens (Q9Y251), Homo sapiens
Manually annotated by BRENDA team
Levy-Adam, F.; Abboud-Jarrous, G.; Guerrini, M.; Beccati, D.; Vlodavsky, I.; Ilan, N.
Identification and characterization of heparin/heparan sulfate binding domains of the endoglycosidase heparanase
J. Biol. Chem.
280
20457-20466
2005
Homo sapiens (Q9Y251), Homo sapiens
Manually annotated by BRENDA team
Vreys, V.; David G.
Mammalian heparanase: what is the message?
J. Cell. Mol. Med.
11
427-452
2007
Homo sapiens (Q9Y251)
Manually annotated by BRENDA team
Bernard, D.; Mehul, B.; Delattre, C.; Simonetti, L.; Thomas-Collignon, A.; Schmidt, R.
Purification and characterization of the endoglycosidase heparanase 1 from human plantar stratum corneum: a key enzyme in epidermal physiology?
J. Invest. Dermatol.
117
1266-1273
2001
Homo sapiens
Manually annotated by BRENDA team
Schubert, S.Y.; Ilan, N.; Shushy, M.; Ben-Izhak, O.; Vlodavsky, I.; Goldshmidt, O.
Human heparanase nuclear localization and enzymatic activity
Lab. Invest.
84
535-544
2004
Rattus norvegicus, Homo sapiens (Q9Y251), Homo sapiens
Manually annotated by BRENDA team
Vlodavsky, I.; Friedmann, Y.; Elkin, M.; Aingorn, H.; Atzmon, R.; Ishai-Michaeli, R.; Bitan, M.; Pappo, O.; Peretz, T.; Michal, I.; Spector, L.; Pecker, I.
Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis
Nat. Med.
5
793-802
1999
Homo sapiens
Manually annotated by BRENDA team
Hammond, E.; Li, C.P.; Ferro, V.
Development of a colorimetric assay for heparanase activity suitable for kinetic analysis and inhibitor screening
Anal. Biochem.
396
112-116
2009
Homo sapiens (Q9Y251)
Manually annotated by BRENDA team
Poon, I.K.; Yee, D.Y.; Jones, A.L.; Wood, R.J.; Davis, D.S.; Freeman, C.; Parish, C.R.; Hulett, M.D.
Histidine-rich glycoprotein binds heparanase and regulates its enzymatic activity and cell surface interactions
Int. J. Biochem. Cell Biol.
42
1507-1516
2010
Homo sapiens (Q9Y251)
Manually annotated by BRENDA team
Peterson, S.B.; Liu, J.
Unraveling the specificity of heparanase utilizing synthetic substrates
J. Biol. Chem.
285
14504-14513
2010
Homo sapiens (Q9Y251)
Manually annotated by BRENDA team
Smith, P.N.; Freeman, C.; Yu, D.; Chen, M.; Gatenby, P.A.; Parish, C.R.; Li, R.W.
Heparanase in primary human osteoblast
J. Orthop. Res.
28
1315-1322
2010
Homo sapiens (Q9Y251), Homo sapiens
Manually annotated by BRENDA team
Zheng, L.D.; Jiang, G.S.; Pu, J.R.; Mei, H.; Dong, J.H.; Hou, X.H.; Tong, Q.S.
Stable knockdown of heparanase expression in gastric cancer cells in vitro
World J. Gastroenterol.
15
5442-5448
2009
Homo sapiens (Q9Y251), Homo sapiens
Manually annotated by BRENDA team
Masola, V.; Gambaro, G.; Tibaldi, E.; Onisto, M.; Abaterusso, C.; Lupo, A.
Regulation of heparanase by albumin and advanced glycation end products in proximal tubular cells
Biochim. Biophys. Acta
1813
1475-1482
2011
Homo sapiens
Manually annotated by BRENDA team
Zhang, Y.; Ryan, D.; Bower, K.; Ilan, N.; Vlodavsky, I.; Laurie, G.
Focus on molecules: Heparanase
Exp. Eye Res.
91
476-477
2010
Homo sapiens (Q9Y251)
Manually annotated by BRENDA team
Barash, U.; Cohen-Kaplan, V.; Arvatz, G.; Gingis-Velitski, S.; Levy-Adam, F.; Nativ, O.; Shemesh, R.; Ayalon-Sofer, M.; Ilan, N.; Vlodavsky, I.
A novel human heparanase splice variant, T5, endowed with protumorigenic characteristics
FASEB J.
24
1239-1248
2010
Homo sapiens
Manually annotated by BRENDA team
Barash, U.; Cohen-Kaplan, V.; Dowek, I.; Sanderson, R.D.; Ilan, N.; Vlodavsky, I.
Proteoglycans in health and disease: new concepts for heparanase function in tumor progression and metastasis
FEBS J.
277
3890-3903
2010
Homo sapiens
Manually annotated by BRENDA team
Miller, J.D.; Clabaugh, S.E.; Smith, D.R.; Stevens, R.B.; Wrenshall, L.E.
Interleukin-2 is present in human blood vessels and released in biologically active form by heparanase
Immunol. Cell Biol.
90
159-167
2012
Homo sapiens
Manually annotated by BRENDA team
Levy-Adam, F.; Feld, S.; Cohen-Kaplan, V.; Shteingauz, A.; Gross, M.; Arvatz, G.; Naroditsky, I.; Ilan, N.; Doweck, I.; Vlodavsky, I.
Heparanase 2 interacts with heparan sulfate with high affinity and inhibits heparanase activity
J. Biol. Chem.
285
28010-28019
2010
Homo sapiens
Manually annotated by BRENDA team
Ramani, V.C.; Yang, Y.; Ren, Y.; Nan, L.; Sanderson, R.D.
Heparanase plays a dual role in driving hepatocyte growth factor (HGF) signaling by enhancing HGF expression and activity
J. Biol. Chem.
286
6490-6499
2011
Homo sapiens
Manually annotated by BRENDA team
Lerner, I.; Hermano, E.; Zcharia, E.; Rodkin, D.; Bulvik, R.; Doviner, V.; Rubinstein, A.M.; Ishai-Michaeli, R.; Atzmon, R.; Sherman, Y.; Meirovitz, A.; Peretz, T.; Vlodavsky, I.; Elkin, M.
Heparanase powers a chronic inflammatory circuit that promotes colitis-associated tumorigenesis in mice
J. Clin. Invest.
121
1709-1721
2011
Homo sapiens
Manually annotated by BRENDA team
Planer, D.; Metzger, S.; Zcharia, E.; Wexler, I.D.; Vlodavsky, I.; Chajek-Shaul, T.
Role of heparanase on hepatic uptake of intestinal derived lipoprotein and fatty streak formation in mice
PLoS ONE
6
e18370
2011
Homo sapiens
Manually annotated by BRENDA team
Wilson, J.C.; Laloo, A.E.; Singh, S.; Ferro, V.
1H NMR spectroscopic studies establish that heparanase is a retaining glycosidase
Biochem. Biophys. Res. Commun.
443
185-188
2014
Homo sapiens
Manually annotated by BRENDA team
Fernandes dos Santos, T.C.; Gomes, A.M.; Paschoal, M.E.; Stelling, M.P.; Rumjanek, V.M.; Junior, A.d.o.R.; Valiante, P.M.; Madi, K.; Pereira de Souza, H.S.; Pavao, M.S.; Castelo-Branco, M.T.
Heparanase expression and localization in different types of human lung cancer
Biochim. Biophys. Acta
1840
2599-2608
2014
Homo sapiens
Manually annotated by BRENDA team
Masola, V.; Zaza, G.; Secchi, M.F.; Gambaro, G.; Lupo, A.; Onisto, M.
Heparanase is a key player in renal fibrosis by regulating TGF-beta expression and activity
Biochim. Biophys. Acta
1843
2122-2128
2014
Homo sapiens
Manually annotated by BRENDA team
Mosulen, S.; Pineda-Lucena, A.; Carbajo, R.J.
Chemical shift assignments and secondary structure of the surrogate domain for drug discovery studies of human heparanase
Biomol. NMR Assign.
9
15-19
2014
Homo sapiens
Manually annotated by BRENDA team
Gozalbes, R.; Mosulen, S.; Orti, L.; Rodriguez-Diaz, J.; Carbajo, R.J.; Melnyk, P.; Pineda-Lucena, A.
Hit identification of novel heparanase inhibitors by structure- and ligand-based approaches
Bioorg. Med. Chem.
21
1944-1951
2013
Homo sapiens
Manually annotated by BRENDA team
Winkler, S.; Schweiger, D.; Wei, Z.; Rajkovic, E.; Kungl, A.J.
Bacterial expression and functional reconstitution of human heparanase
Carbohydr. Res.
389
72-77
2014
Homo sapiens
Manually annotated by BRENDA team
Lerner, I.; Zcharia, E.; Neuman, T.; Hermano, E.; Rubinstein, A.M.; Vlodavsky, I.; Elkin, M.
Heparanase is preferentially expressed in human psoriatic lesions and induces development of psoriasiform skin inflammation in mice
Cell. Mol. Life Sci.
71
2347-2357
2014
Homo sapiens, Mus musculus, Mus musculus BALB/c
Manually annotated by BRENDA team
Ohmae, M.; Fujita, Y.; Takada, J.; Kimura, S.
Development of novel inhibitors specific for human heparanase-1
Chem. Lett.
42
797-798
2013
Homo sapiens
-
Manually annotated by BRENDA team
Hammond, E.; Handley, P.; Dredge, K.; Bytheway, I.
Mechanisms of heparanase inhibition by the heparan sulfate mimetic PG545 and three structural analogues
FEBS Open Bio
3
346-351
2013
Homo sapiens
Manually annotated by BRENDA team
Hammond, E.; Khurana, A.; Shridhar, V.; Dredge, K.
The role of heparanase and sulfatases in the modification of heparan sulfate proteoglycans within the tumour microenvironment and opportunities for novel cancer therapeutics
Front. Oncol.
4
195
2014
Homo sapiens
Manually annotated by BRENDA team
Gandhi, N.; Freeman, C.; Parish, C.; Mancera, R.
Computational analyses of the catalytic and heparin-binding sites and their interactions with glycosaminoglycans in glycoside hydrolase family 79 endo-D-glucuronidase (heparanase)
Glycobiology
22
35-55
2012
Homo sapiens (Q9Y251), Homo sapiens
Manually annotated by BRENDA team
Thompson, C.A.; Purushothaman, A.; Ramani, V.C.; Vlodavsky, I.; Sanderson, R.D.
Heparanase regulates secretion, composition, and function of tumor cell-derived exosomes
J. Biol. Chem.
288
10093-10099
2013
Homo sapiens
Manually annotated by BRENDA team
Vlodavsky, I.; Blich, M.; Li, J.P.; Sanderson, R.D.; Ilan, N.
Involvement of heparanase in atherosclerosis and other vessel wall pathologies
Matrix Biol.
32
241-251
2013
Homo sapiens
Manually annotated by BRENDA team
He, Y.Q.; Sutcliffe, E.L.; Bunting, K.L.; Li, J.; Goodall, K.J.; Poon, I.K.; Hulett, M.D.; Freeman, C.; Zafar, A.; McInnes, R.L.; Taya, T.; Parish, C.R.; Rao, S.
The endoglycosidase heparanase enters the nucleus of T lymphocytes and modulates H3 methylation at actively transcribed genes via the interplay with key chromatin modifying enzymes
Transcription
3
130-145
2012
Homo sapiens
Manually annotated by BRENDA team
Melo, C.M.; Tersariol, I.L.; Nader, H.B.; Pinhal, M.A.; Lima, M.A.
Development of new methods for determining the heparanase enzymatic activity
Carbohydr. Res.
412
66-70
2015
Homo sapiens (Q9Y251)
Manually annotated by BRENDA team
Loka, R.S.; Yu, F.; Sletten, E.T.; Nguyen, H.M.
Design, synthesis, and evaluation of heparan sulfate mimicking glycopolymers for inhibiting heparanase activity
Chem. Commun. (Camb.)
53
9163-9166
2017
Homo sapiens (Q9Y251)
Manually annotated by BRENDA team
Vlodavsky, I.; Singh, P.; Boyango, I.; Gutter-Kapon, L.; Elkin, M.; Sanderson, R.D.; Ilan, N.
Heparanase from basic research to therapeutic applications in cancer and inflammation
Drug Resist. Updat.
29
54-75
2016
Homo sapiens (Q9Y251), Homo sapiens
Manually annotated by BRENDA team
Messore, A.; Madia, V.N.; Pescatori, L.; Saccoliti, F.; Tudino, V.; De Leo, A.; Bortolami, M.; De Vita, D.; Scipione, L.; Pepi, F.; Costi, R.; Rivara, S.; Scalvini, L.; Mor, M.; Ferrara, F.F.; Pavoni, E.; Roscilli, G.; Cassinelli, G.; Milazzo, F.M.; Battistuzzi, G.; Di Santo, R.; Giannini, G.
Novel symmetrical benzazolyl derivatives endowed with potent anti-heparanase activity
J. Med. Chem.
61
10834-10859
2018
Homo sapiens (Q9Y251)
Manually annotated by BRENDA team
Wu, L.; Viola, C.M.; Brzozowski, A.M.; Davies, G.J.
Structural characterization of human heparanase reveals insights into substrate recognition
Nat. Struct. Mol. Biol.
22
1016-1022
2015
Homo sapiens (Q9Y251), Homo sapiens
Manually annotated by BRENDA team
Bohdan, N.; Espin, S.; Aguila, S.; Teruel-Montoya, R.; Vicente, V.; Corral, J.; Martinez-Martinez, I.
Heparanase activates antithrombin through the binding to its heparin binding site
PLoS ONE
11
e0157834
2016
Homo sapiens (Q9Y251)
Manually annotated by BRENDA team
Ushakov, V.; Tsidulko, A.; De La Bourdonnaye, G.; Kazanskaya, G.; Volkov, A.; Kiselev, R.; Kobozev, V.; Kostromskaya, D.; Gaytan, A.; Krivoshapkin, A.; Aidagulova, S.; Grigorieva, E.
Heparan sulfate biosynthetic system is inhibited in human glioma due to EXT1/2 and HS6ST1/2 down-regulation
Int. J. Mol. Sci.
18
2301
2017
Homo sapiens (Q9Y251)
Manually annotated by BRENDA team