InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: HPSE

Summary

InnateDB Protein

IDBP-27686.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

HPSE

Protein Name

heparanase

Synonyms

HPA; HPA1; HPR1; HPSE1; HSE1;

Species

Homo sapiens

Ensembl Protein

ENSP00000308107

InnateDB Gene

IDBG-27684 (HPSE)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:12213822, ECO:0000269PubMed:12773484, ECO:0000269PubMed:15044433, ECO:0000269PubMed:16452201, ECO:0000269PubMed:18557927, ECO:0000269PubMed:18798279, ECO:0000269PubMed:19244131, ECO:0000269PubMed:20097882, ECO:0000269PubMed:20181948, ECO:0000269PubMed:20309870, ECO:0000269PubMed:20561914, ECO:0000269PubMed:21131364}.

Subcellular Localization

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). {ECO:0000250}.

Disease Associations

Tissue Specificity

Highly expressed in placenta and spleen and weakly expressed in lymph node, thymus, peripheral blood leukocytes, bone marrow, endothelial cells, fetal liver and tumor tissues. Also expressed in hair follicles, specifically in both Henle's and Huxley's layers of inner the root sheath (IRS) at anagen phase. {ECO:0000269PubMed:10395326, ECO:0000269PubMed:10405343, ECO:0000269PubMed:10764835, ECO:0000269PubMed:18557927, ECO:0000269PubMed:20309870}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 2 experimentally validated interaction(s) in this database.

Experimentally validated
Total	2 [view]
Protein-Protein	2 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004566	beta-glucuronidase activity
GO:0005515	protein binding
GO:0016798	hydrolase activity, acting on glycosyl bonds
GO:0030305	heparanase activity
GO:0045545	syndecan binding
GO:0046983	protein dimerization activity

Biological Process

GO:0005975	carbohydrate metabolic process
GO:0006027	glycosaminoglycan catabolic process
GO:0006029	proteoglycan metabolic process
GO:0007160	cell-matrix adhesion
GO:0010575	positive regulation vascular endothelial growth factor production
GO:0030194	positive regulation of blood coagulation
GO:0030200	heparan sulfate proteoglycan catabolic process
GO:0030203	glycosaminoglycan metabolic process
GO:0033690	positive regulation of osteoblast proliferation
GO:0044281	small molecule metabolic process
GO:0051797	regulation of hair follicle development
GO:0051897	positive regulation of protein kinase B signaling

Cellular Component

GO:0005576	extracellular region
GO:0005634	nucleus
GO:0005764	lysosome
GO:0005765	lysosomal membrane
GO:0016020	membrane
GO:0043202	lysosomal lumen
GO:0043231	intracellular membrane-bounded organelle