HPSE

Heparan sulfate proteoglycans are major components of the basement membrane and extracellular matrix. The protein encoded by this gene is an enzyme that cleaves heparan sulfate proteoglycans to permit cell movement through remodeling of the extracellular matrix. In addition, this cleavage can release bioactive molecules from the extracellular matrix. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

Heparanase

Endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs) into heparan sulfate side chains and core proteoglycans. Participates in extracellular matrix (ECM) degradation and remodeling. Selectively 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. Can also cleave the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying a 2-O-sulfo group, but not linkages between a glucuronic acid unit and a 2-O-sulfated iduronic acid moiety. It is essentially inactive at neutral pH but becomes active under acidic conditions such as during tumor invasion and in inflammatory processes. Facilitates cell migration associated with metastasis, wound healing and inflammation. Enhances shedding of syndecans, and increases endothelial invasion and angiogenesis in myelomas. Acts as procoagulant by increasing the generation of activation factor X in the presence of tissue factor and activation factor VII. Increases cell adhesion to the extracellular matrix (ECM), independent of its enzymatic activity. Induces AKT1/PKB phosphorylation via lipid rafts increasing cell mobility and invasion. Heparin increases this AKT1/PKB activation. Regulates osteogenesis. Enhances angiogenesis through up-regulation of SRC-mediated activation of VEGF. Implicated in hair follicle inner root sheath differentiation and hair homeostasis.

Angiogenesis involved in wound healing Source: GO_Central
Cell-matrix adhesion Source: UniProtKB
Establishment of endothelial barrier Source: Ensembl
Factor XII activation Source: ComplexPortal
Heparan sulfate proteoglycan catabolic process Source: ComplexPortal
Heparin metabolic process Source: Ensembl
Inflammatory response Source: ComplexPortal
Positive regulation of angiogenesis Source: ComplexPortal
Positive regulation of autophagy Source: ComplexPortal
Positive regulation of blood coagulation Source: ComplexPortal
Positive regulation of cell-matrix adhesion Source: ComplexPortal
Positive regulation of cell migration Source: ComplexPortal
Positive regulation of cell population proliferation Source: ComplexPortal
Positive regulation of hair follicle development Source: Ensembl
Positive regulation of osteoblast proliferation Source: UniProtKB
Positive regulation of protein kinase B signaling Source: UniProtKB
Positive regulation of substrate adhesion-dependent cell spreading Source: ComplexPortal
Positive regulation of vascular endothelial growth factor production Source: UniProtKB
Protein transmembrane transport Source: Ensembl
Proteoglycan metabolic process Source: ProtInc
Regulation of hair follicle development Source: UniProtKB
Response to organic substance Source: Ensembl
Vascular wound healing Source: Ensembl

Nucleus; Secreted; Lysosome membrane. Proheparanase is secreted via vesicles of the Golgi. Interacts with cell membrane heparan sulfate proteoglycans (HSPGs). Endocytosed and accumulates in endosomes. Transferred to lysosomes where it is proteolytically cleaved to produce the active enzyme. Under certain stimuli, transferred to the cell surface. Associates with lipid rafts. Colocalizes with SDC1 in endosomal/lysosomal vesicles. Accumulates in perinuclear lysosomal vesicles. Heparin retains proheparanase in the extracellular medium (By similarity).

Proteolytically processed. The cleavage of the 65 kDa form leads to the generation of a linker peptide, and 8 kDa and 50 kDa products. The active form, the 8/50 kDa heterodimer, is resistant to degradation. Complete removal of the linker peptide appears to be a prerequisite to the complete activation of the enzyme.
N-glycosylated. Glycosylation of the 50 kDa subunit appears to be essential for its solubility.