Tchem HPSE Heparanase

Protein Summary

Description

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 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. Heparan sulfate proteoglycans are major components of the basement membrane and extracellular matrix. The protein encoded by this gene is an enzyme that cleaves heparan sulfate proteoglycans to permit cell movement through remodeling of the extracellular matrix. In addition, this cleavage can release bioactive molecules from the extracellular matrix. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

Uniprot Accession IDs

• Q9Y251
• A9JIG7
• C7F7I3
• C7F7I4
• E9PCA9
• E9PGR1
• Q53GE5
• Q9UL39

Gene Name

• HPSE

Ensembl ID

• ENST00000311412
• ENSP00000308107
• ENSG00000173083
• ENST00000405413
• ENSP00000384262
• ENST00000509906
• ENSP00000421038
• ENST00000512196
• ENSP00000423265
• ENST00000513463
• ENSP00000421365

Symbol

• HEP
• HPA
• HPA1
• HPR1
• HPSE1
• HSE1
• HPA
• HPA1
• HPR1
• HSE1
• HPSE1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
histone modification site profile	0.8
transcription factor perturbation	0.74
interacting protein	0.73
biological process	0.72
cellular component	0.72

Protein Classes

PANTHER Classes

Protein / Hydrolase / Glycosidase / Heparanase

DTO Classes

Protein / Enzyme / Hydrolase / Glycosidase / Heparanase

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 783.64   (req: < 5)

Gene RIFs: 337   (req: <= 3)

Antibodies: 512   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 783.64   (req: >= 5)

Gene RIFs: 337   (req: > 3)

Antibodies: 512   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 17

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 125

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0