| Post Translational Modifications | 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. |
| Function | 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 a 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. |
| Protein Name | HeparanaseEndo-GlucoronidaseHeparanase-1Hpa1 Cleaved Into - Heparanase 8 Kda Subunit - Heparanase 50 Kda Subunit |
| Database Links | Reactome: R-HSA-2024096Reactome: R-HSA-6798695 |
| Cellular Localisation | Lysosome MembranePeripheral Membrane ProteinSecretedNucleusProheparanase Is Secreted Via Vesicles Of The GolgiInteracts With Cell Membrane Heparan Sulfate Proteoglycans (Hspgs)Endocytosed And Accumulates In EndosomesTransferred To Lysosomes Where It Is Proteolytically Cleaved To Produce The Active EnzymeUnder Certain StimuliTransferred To The Cell SurfaceAssociates With Lipid RaftsColocalizes With Sdc1 In Endosomal/Lysosomal VesiclesAccumulates In Perinuclear Lysosomal VesiclesHeparin Retains Proheparanase In The Extracellular Medium |
| Alternative Protein Names | Heparanase proteinEndo-Glucoronidase proteinHeparanase-1 proteinHpa1 Cleaved Into - Heparanase 8 Kda Subunit - Heparanase 50 Kda Subunit proteinHPSE proteinHEP proteinHPA proteinHPA1 proteinHPR1 proteinHPSE1 proteinHSE1 protein |
Information sourced from Uniprot.org
