InnateDB Protein
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IDBP-183402.6
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Last Modified
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2014-10-13 [Report errors or provide feedback]
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Gene Symbol
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Hpse
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Protein Name
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heparanase
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Synonyms
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Hpa; Hpr1; HSE1;
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Species
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Mus musculus
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Ensembl Protein
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ENSMUSP00000044072
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InnateDB Gene
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IDBG-183400 (Hpse)
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Protein Structure
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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:15677344, ECO:0000269PubMed:15793281, ECO:0000269PubMed:17689495, ECO:0000269PubMed:18589009}.
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Subcellular Localization |
Lysosome membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Secreted {ECO:0000269PubMed:15793281}. Nucleus {ECO:0000269PubMed:15793281}. 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. Colocalizes with SDC1 in endosomal/lysosomal vesicles. Accumulates in perinuclear lysosomal vesicles. Heparin retains proheparanase in the extracellular medium (By similarity). Associates with lipid rafts. {ECO:0000250}.
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Disease Associations |
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Tissue Specificity |
Expressed in skin, mainly in the stratum granulosum and the first layer of the stratum corneum in the upper part of the epidermis. Also detected in hair follicles and in sebaceous glands. {ECO:0000269PubMed:15793281, ECO:0000269PubMed:18589009}.
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Comments |
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Number of Interactions
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This gene and/or its encoded proteins are associated with 0 experimentally validated interaction(s) in this database.
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Molecular Function |
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Biological Process |
GO:0005975
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carbohydrate metabolic process
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GO:0007160
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cell-matrix adhesion
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GO:0010575
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positive regulation vascular endothelial growth factor production
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GO:0030194
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positive regulation of blood coagulation
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GO:0030200
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heparan sulfate proteoglycan catabolic process
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GO:0033690
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positive regulation of osteoblast proliferation
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GO:0042060
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wound healing
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GO:0051797
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regulation of hair follicle development
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GO:0051798
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positive regulation of hair follicle development
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GO:0051897
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positive regulation of protein kinase B signaling
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GO:0060055
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angiogenesis involved in wound healing
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GO:0061042
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vascular wound healing
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Cellular Component |
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PDB ID |
MGI:1343124
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InterPro |
IPR005199
Glycoside hydrolase, family 79
IPR017853
Glycoside hydrolase, superfamily
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PFAM |
PF03662
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PRINTS |
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PIRSF |
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SMART |
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TIGRFAMs |
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Modification |
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SwissProt |
Q6YGZ1
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PhosphoSite |
PhosphoSite-Q6YGZ1
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TrEMBL |
D3Z3C3
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UniProt Splice Variant |
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Entrez Gene |
15442
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UniGene |
Mm.265786
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RefSeq |
NP_690016
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MGI ID |
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MGI Symbol |
Hpse
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OMIM |
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CCDS |
CCDS19466
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HPRD |
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IMGT |
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EMBL |
AC161510
AF359507
AK040471
AK154628
AY077467
AY151051
BC138782
BC138784
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GenPept |
AAI38783
AAI38785
AAL76083
AAN41636
AAQ15188
BAC30600
BAE32725
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