Heparanase (HPA)

HPSE; HPR1; HPSE1; HSE1; Endo-glucoronidase;

SPN	W101
HGNC	5164
MGI	1343124
PubMed	23430739
RGD	61969
UniProt	Q9Y251
Wiki	Heparanase

Heparanase is an endo-β-D-glucuronidase that catalyzes the hydrolytic cleavage of the β-1,4-glycosidic bond between a D-glucuronate and a D-glucosamine in heparan sulfate. The physiological role of heparanase is simply to degrade heparan sulfate but this activity can take many turns.The protein is originally synthesised in an inactive 65 kDa proheparanase form in the golgi apparatus and transferred to late endosomes/lysosomes for transport to the cell-surface. In the lysosome it is proteolytically processed into its active form. The 8 kDa and 50 kDa fragments form a heterodimer and it is this heterodimer that constitutes the active heparanase molecule. The linker protein is so called because prior to its excision it physically links the 8 kDa and 50 kDa proheparanase fragments.

Reference

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Biochem. Biophys. Res. Commun. 261:183-187(1999) [PubMed] [Europe PMC] [Abstract]

"Human heparanase. Purification, characterization, cloning, and expression."
J. Biol. Chem. 274:24153-24160(1999) [PubMed] [Europe PMC] [Abstract]

"Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis."
Nat. Med. 5:793-802(1999) [PubMed] [Europe PMC] [Abstract]

"Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis."
Nat. Med. 5:803-809(1999) [PubMed] [Europe PMC] [Abstract]

"Heparanase expression in invasive trophoblasts and acute vascular damage."
Glycobiology 10:467-475(2000) [PubMed] [Europe PMC] [Abstract]

"Molecular properties and involvement of heparanase in cancer progression and mammary gland morphogenesis."
J. Mammary Gland Biol. Neoplasia 6:311-322(2001) [PubMed] [Europe PMC] [Abstract]

"Biochemical characterization of the active heterodimer form of human heparanase (Hpa1) protein expressed in insect cells."
Biochem. J. 373:423-435(2003) [PubMed] [Europe PMC] [Abstract]

"Cloning, expression, and characterization of an alternatively spliced variant of human heparanase."
Biochem. Biophys. Res. Commun. 354:33-38(2007) [PubMed] [Europe PMC] [Abstract]

"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Identification of active-site residues of the pro-metastatic endoglycosidase heparanase."
Biochemistry 39:15659-15667(2000) [PubMed] [Europe PMC] [Abstract]

"Human heparanase is localized within lysosomes in a stable form."
Exp. Cell Res. 281:50-62(2002) [PubMed] [Europe PMC] [Abstract]

"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) [PubMed] [Europe PMC] [Abstract]

"Activation, processing and trafficking of extracellular heparanase by primary human fibroblasts."
J. Cell Sci. 115:2179-2187(2002) [PubMed] [Europe PMC] [Abstract]

"Heterodimer formation is essential for heparanase enzymatic activity."
Biochem. Biophys. Res. Commun. 308:885-891(2003) [PubMed] [Europe PMC] [Abstract]

"Heparanase mediates cell adhesion independent of its enzymatic activity."
FASEB J. 17:1015-1025(2003) [PubMed] [Europe PMC] [Abstract]

"Secretion of heparanase protein is regulated by glycosylation in human tumor cell lines."
J. Biol. Chem. 279:2697-2703(2004) [PubMed] [Europe PMC] [Abstract]

"Heparanase induces endothelial cell migration via protein kinase B/Akt activation."
J. Biol. Chem. 279:23536-23541(2004) [PubMed] [Europe PMC] [Abstract]

"Heparanase uptake is mediated by cell membrane heparan sulfate proteoglycans."
J. Biol. Chem. 279:44084-44092(2004) [PubMed] [Europe PMC] [Abstract]

"Processing and activation of latent heparanase occurs in lysosomes."
J. Cell Sci. 117:2249-2258(2004) [PubMed] [Europe PMC] [Abstract]

"Heparanase processing by lysosomal/endosomal protein preparation."
FEBS Lett. 579:2334-2338(2005) [PubMed] [Europe PMC] [Abstract]

"Site-directed mutagenesis, proteolytic cleavage, and activation of human proheparanase."
J. Biol. Chem. 280:13568-13575(2005) [PubMed] [Europe PMC] [Abstract]

"Identification and characterization of heparin/heparan sulfate binding domains of the endoglycosidase heparanase."
J. Biol. Chem. 280:20457-20466(2005) [PubMed] [Europe PMC] [Abstract]

"Heparanase induces vascular endothelial growth factor expression: correlation with p38 phosphorylation levels and Src activation."
Cancer Res. 66:1455-1463(2006) [PubMed] [Europe PMC] [Abstract]

"Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach."
Mol. Cell. Proteomics 5:226-233(2006) [PubMed] [Europe PMC] [Abstract]

"Heparanase 1: a key participant of inner root sheath differentiation program and hair follicle homeostasis."
Exp. Dermatol. 17:1017-1023(2008) [PubMed] [Europe PMC] [Abstract]

"Heparanase induces VEGF C and facilitates tumor lymphangiogenesis."
Int. J. Cancer 123:2566-2573(2008) [PubMed] [Europe PMC] [Abstract]

"Structure-function approach identifies a COOH-terminal domain that mediates heparanase signaling."
Cancer Res. 69:1758-1767(2009) [PubMed] [Europe PMC] [Abstract]

"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]

"Heparanase-enhanced shedding of syndecan-1 by myeloma cells promotes endothelial invasion and angiogenesis."
Blood 115:2449-2457(2010) [PubMed] [Europe PMC] [Abstract]

"Heparanase enhances the generation of activated factor X in the presence of tissue factor and activated factor VII."
Haematologica 95:1927-1934(2010) [PubMed] [Europe PMC] [Abstract]

"Histidine-rich glycoprotein binds heparanase and regulates its enzymatic activity and cell surface interactions."
Int. J. Biochem. Cell Biol. 42:1507-1516(2010) [PubMed] [Europe PMC] [Abstract]

"Unraveling the specificity of heparanase utilizing synthetic substrates."
J. Biol. Chem. 285:14504-14513(2010) [PubMed] [Europe PMC] [Abstract]

"Heparanase 2 interacts with heparan sulfate with high affinity and inhibits heparanase activity."
J. Biol. Chem. 285:28010-28019(2010) [PubMed] [Europe PMC] [Abstract]

"Heparanase in primary human osteoblasts."
J. Orthop. Res. 28:1315-1322(2010) [PubMed] [Europe PMC] [Abstract]

"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) [PubMed] [Europe PMC] [Abstract]

"Heparanase mRNA expression and point mutation in hepatocellular carcinoma."
World J. Gastroenterol. 10:2795-2799(2004) [PubMed] [Europe PMC] [Abstract]