Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol HPSE contributors: mct - updated : 24-08-2016
HGNC name heparanase
HGNC id 5164
Location 4q21.22      Physical location : 84.216.469 - 84.256.306
Synonym name
  • endo-beta-glucuronidase
  • heparanase-1
  • Synonym symbol(s) HPA, HSE1, HPR1, HPSE1, HPR11
    EC.number 3.2.1.166
    DNA
    TYPE functioning gene
    STRUCTURE 42.70 kb     13 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence
    text structure
  • a 185-bp sequence within the 3' UTR that mediates heparanase down-regulation, and characterized an adenine (A)/uracil (U)-rich consensus element (ARE) within this region; deletion of the entire 185-bp region or the ARE eliminated the inhibitory effect of the 3' UTR, resulting in elevated heparanase levels and formation of tumor
  • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 4668 61.15 543 - 2007 17208203
    11 - 4446 51.6 469 - 2007 17208203
    ex9-10del
    12 - 4630 61.15 543 - 2007 17208203
    12 - 4388 54.7 485 - 2007 17208203
  • splice 5 isoform, T5
  • escaped proteolytic cleavage, was devoid of escaped proteolytic cleavage, of Heparan sulfate (HS) degradation activity and exhibited diffused rather than granular cellular localization degradation activity and exhibited diffused rather than granular cellular localization
  • T5 is a functional, pro-tumorigenic entity
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen    
    Digestiveesophagus   highly
     intestinesmall intestine  highly
    Reproductivefemale systemplacenta  highly
     male systemprostate   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoietic    
    Lymphoid    
    Muscularsmooth   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticplatelet
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal signal-sequence
  • two putative transmembrane segments (TM) at the N and C termini
  • six putative N-linked glycosylation sites
  • three potential heparin binding domains, and one of these at the N terminus of the 50-kDa active heparanase subunit
  • two different functional domains within the heparanase enzyme (the enzyme active site and a separate site) contribute to events leading to enhanced HGF signaling
  • HOMOLOGY
    Homologene
    FAMILY
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,lysosome
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • endoglyosidase cleaving heparan sulfate proteoglycan at a limited mumber of sites along the polysaccharide chain
  • essential in the disassembly of the extracellular matrix (ECM) by invading cells
  • cleaves heparan sulfate in the extracellular matrix (ECM) and hence participates in ECM degradation and remodeling
  • involved in glycosaminoglycan chain synthesis or modifications
  • significant involvement of heparanase in diabetic complications
  • helps drive exosome secretion, alters exosome composition, and facilitates production of exosomes that impact both tumor and host cell behavior, thereby promoting tumor progression
  • only known mammalian endoglycosidase capable of degrading heparan sulfate glycosaminoglycan, both in extracellular space and within the cells
  • important for palate formation because it mediated degradation of the ECM (extracellular matrix) of palatal shelves
  • involved in mechanisms of metastatic tumor cell migration.
  • role for heparanase in inflammatory cell trafficking that appears to require enzymatic activity
  • is a key player in renal fibrosis since it interacts with the regulation and the effects of TGFB1
  • plays a central role in processes of placentation
  • is a modulator of the SDC1-SDCBP-PDCD6IP pathway, fostering endosomal membrane budding and the biogenesis of exosomes by trimming the heparan sulfate chains on syndecans
  • dual function for HPSE in malignant melanoma with a protumorigenic extracellular activity and a tumor-suppressive nuclear action
  • predominant enzyme in mammals capable of cleaving heparan sulfate, an activity highly implicated in cellular invasion and tumor metastasis
  • role for heparanase in modulating autophagy in normal and malignant cells, thereby conferring growth advantages as well as resistance to chemotherapy
  • CELLULAR PROCESS cell life, proliferation/growth
    cell communication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • involved in hypoxia-induced neovascularization through promoting VEGFA expression
  • vHPSE stimulates the exosomal secretion of SDCBP, SDC1 and certain other exosomal cargo, such as CD63, in a concentration-dependent manner
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in prostate cancer
    constitutional     --over  
    may represent a physiological mechanism involved in neural cellular differentiation
    tumoral     --over  
    in ovarian cancer (OC), and contributes to the proliferation and metastasis of OC
    constitutional     --over  
    in preeclamptic placentas compared to normal healthy controls, suggesting its role in the development of preeclampsia
    tumoral     --low  
    by DNA methylation of heparanase promoter that influences its expression and associated with the progression of human breast cancer
    tumoral     --over  
    and regulates proliferation in GH-secreting pituitary tumor cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveovary
    might be a potent molecular target for OC treatment
    neurosensorialvisualdegenerative
    may be a new therapeutic target for hypoxia-induced neovascularization retinal diseases
    ANIMAL & CELL MODELS