InnateDB Protein
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IDBP-293300.4
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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; HPA1; HPR1; HPSE1; HSE1;
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Species
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Homo sapiens
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Ensembl Protein
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ENSP00000384262
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InnateDB Gene
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IDBG-27684 (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: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}.
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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}.
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Disease Associations |
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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}.
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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 2 experimentally validated interaction(s) in this database.
Experimentally validated |
Total |
2
[view]
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Protein-Protein |
2
[view]
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Protein-DNA |
0
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Protein-RNA |
0
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DNA-DNA |
0
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RNA-RNA |
0
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DNA-RNA |
0
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Molecular Function |
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Biological Process |
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Cellular Component |
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PDB ID |
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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 |
Q9Y251
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PhosphoSite |
PhosphoSite-Q9Y251
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TrEMBL |
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UniProt Splice Variant |
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Entrez Gene |
10855
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UniGene |
Hs.627092
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RefSeq |
NP_006656
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HUGO |
HGNC:5164
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OMIM |
604724
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CCDS |
CCDS3602
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HPRD |
05286
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IMGT |
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EMBL |
AC114781
AF084467
AF144325
AF152376
AF155510
AF165154
AK222986
AM419200
AY948074
BC051321
GQ337901
GQ337902
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GenPept |
AAD41342
AAD45379
AAD45669
AAD54516
AAD54941
AAH51321
AAX47106
ACT98237
ACT98238
BAD96706
CAL91960
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