Names & Taxonomy

Uniprot ID:
Q9Y251
Entry Name:
HPSE_HUMAN
Status:
reviewed
Protein Names:
Heparanase (EC 3.2.1.166) (Endo-glucoronidase) (Heparanase-1) (Hpa1) [Cleaved into: Heparanase 8 kDa subunit; Heparanase 50 kDa subunit]
Gene Names:
HPSE HEP HPA HPA1 HPR1 HPSE1 HSE1
Gene Names Primary:
HPSE
Organism:
Homo sapiens (Human)

Structure

Length:
543
Sequence:
MLLRSKPALPPPLMLLLLGPLGPLSPGALPRPAQAQDVVDLDFFTQEPLHLVSPSFLSVTIDANLATDPRFLILLGSPKLRTLARGLSPAYLRFGGTKTDFLIFDPKKESTFEERSYWQSQVNQDICKYGSIPPDVEEKLRLEWPYQEQLLLREHYQKKFKNSTYSRSSVDVLYTFANCSGLDLIFGLNALLRTADLQWNSSNAQLLLDYCSSKGYNISWELGNEPNSFLKKADIFINGSQLGEDFIQLHKLLRKSTFKNAKLYGPDVGQPRRKTAKMLKSFLKAGGEVIDSVTWHHYYLNGRTATKEDFLNPDVLDIFISSVQKVFQVVESTRPGKKVWLGETSSAYGGGAPLLSDTFAAGFMWLDKLGLSARMGIEVVMRQVFFGAGNYHLVDENFDPLPDYWLSLLFKKLVGTKVLMASVQGSKRRKLRVYLHCTNTDNPRYKEGDLTLYAINLHNVTKYLRLPYPFSNKQVDKYLLRPLGPHGLLSKSVQLNGLTLKMVDDQTLPPLMEKPLRPGSSLGLPAFSYSFFVIRNAKVAACI
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Lysosome membrane; Peripheral membrane protein. Secreted. Nucleus. Note=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).

Function

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 procoagulant by increasing the generation of activation factor X in the presence of tissue factor and activation factor VII. Increases cell adhesion to the extacellular 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.
Catalytic Activity:
Endohydrolysis of (1->4)-beta-D-glycosidic bonds of heparan sulfate chains in heparan sulfate proteoglycan.
Enzyme Regulation:
ENZYME REGULATION: Inhibited by EDTA, laminarin sulfate and, to a lower extent, by heparin and sulfamin and activated by calcium and magnesium.
Active Site:
ACT_SITE 225 225 Proton donor.
Cross Reference Drug Bank:
DB06779 DB01109
Gene Ontology Go:
extracellular region
intracellular membrane-bounded organelle
lysosomal lumen
lysosomal membrane
lysosome
membrane raft
nucleoplasm
nucleus
beta-glucuronidase activity
heparanase activity
protein dimerization activity
syndecan binding
carbohydrate metabolic process
cell-matrix adhesion
glycosaminoglycan catabolic process
glycosaminoglycan metabolic process
heparan sulfate proteoglycan catabolic process
positive regulation of blood coagulation
positive regulation of hair follicle development
positive regulation of osteoblast proliferation
positive regulation of protein kinase B signaling
positive regulation of vascular endothelial growth factor production
proteoglycan metabolic process
regulation of hair follicle development
small molecule metabolic process
vascular wound healing
Gene Ontology Biological Process:
carbohydrate metabolic process
cell-matrix adhesion
glycosaminoglycan catabolic process
glycosaminoglycan metabolic process
heparan sulfate proteoglycan catabolic process
positive regulation of blood coagulation
positive regulation of hair follicle development
positive regulation of osteoblast proliferation
positive regulation of protein kinase B signaling
positive regulation of vascular endothelial growth factor production
proteoglycan metabolic process
regulation of hair follicle development
small molecule metabolic process
vascular wound healing
Gene Ontology Molecular Function:
beta-glucuronidase activity
heparanase activity
protein dimerization activity
syndecan binding
Gene Ontology Cellular Component:
extracellular region
intracellular membrane-bounded organelle
lysosomal lumen
lysosomal membrane
lysosome
membrane raft
nucleoplasm
nucleus
Keywords:
3D-structure
Alternative splicing
Calcium
Cell adhesion
Complete proteome
Direct protein sequencing
Glycoprotein
Hydrolase
Lysosome
Magnesium
Membrane
Nucleus
Polymorphism
Reference proteome
Secreted
Signal

Publication

PubMed ID:
10405343 10446189 10395325 10395326 10764835 11547900 12713442 17208203 15815621 15489334 11123890 12441129 12213822 11973358 12927802 12773484 14573609 15044433 15292202 15126626 15848168 15659389 15760902 16452201 16263699 18557927 18798279 19244131 19159218 20097882 20634491 20561914 20181948 20576607 20309870 21131364 15334672