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Aliases for HPSE Gene

Aliases for HPSE Gene

  • Heparanase 2 3 5
  • Endo-Glucoronidase 3 4
  • Heparanase-1 3 4
  • HPSE1 3 4
  • HPA1 3 4
  • HPR1 3 4
  • HSE1 3 4
  • HPA 3 4
  • EC 3.2.1.166 4
  • HEP 4

External Ids for HPSE Gene

Previous GeneCards Identifiers for HPSE Gene

  • GC04M084138
  • GC04M084507
  • GC04M084672
  • GC04M084570
  • GC04M084435
  • GC04M084213
  • GC04M079959

Summaries for HPSE Gene

Entrez Gene Summary for HPSE Gene

  • 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]

GeneCards Summary for HPSE Gene

HPSE (Heparanase) is a Protein Coding gene. Diseases associated with HPSE include israeli tick typhus and urofacial syndrome 1. Among its related pathways are Glycosaminoglycan degradation and Metabolism. GO annotations related to this gene include protein dimerization activity and syndecan binding. An important paralog of this gene is HPSE2.

UniProtKB/Swiss-Prot for HPSE Gene

  • 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.

Tocris Summary for HPSE Gene

  • Antiangiogenic agents are compounds which prevent angiogenesis in vitro and/or in vivo. Angiogenesis inhibitors may be endogenous or synthetic; others are obtained from diet, for example resveratrol.

Gene Wiki entry for HPSE Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HPSE Gene

Genomics for HPSE Gene

Regulatory Elements for HPSE Gene

Enhancers for HPSE Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around HPSE on UCSC Golden Path with GeneCards custom track

Promoters for HPSE Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around HPSE on UCSC Golden Path with GeneCards custom track

Genomic Location for HPSE Gene

Chromosome:
4
Start:
83,292,461 bp from pter
End:
83,335,153 bp from pter
Size:
42,693 bases
Orientation:
Minus strand

Genomic View for HPSE Gene

Genes around HPSE on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HPSE Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HPSE Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HPSE Gene

Proteins for HPSE Gene

  • Protein details for HPSE Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y251-HPSE_HUMAN
    Recommended name:
    Heparanase
    Protein Accession:
    Q9Y251
    Secondary Accessions:
    • A9JIG7
    • C7F7I3
    • C7F7I4
    • E9PCA9
    • E9PGR1
    • Q53GE5
    • Q9UL39

    Protein attributes for HPSE Gene

    Size:
    543 amino acids
    Molecular mass:
    61149 Da
    Quaternary structure:
    • Heterodimer; heterodimer formation between the 8 kDa and the 50 kDa subunits is required for enzyme activity. Interacts with TF; the interaction, inhibited by heparin, enhances the generation of activated factor X and activates coagulation. Interacts with HRG; the interaction is enhanced at acidic pH, partially inhibits binding of HPSE to cell surface receptors and modulates its enzymatic activity. Interacts with SDC1; the interaction enhances the shedding of SDC1. Interacts with HPSE2.

    Three dimensional structures from OCA and Proteopedia for HPSE Gene

    Alternative splice isoforms for HPSE Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for HPSE Gene

Proteomics data for HPSE Gene at MOPED

Post-translational modifications for HPSE Gene

  • N-glycosylated. Glycosylation of the 50 kDa subunit appears to be essential for its solubility.
  • Proteolytically processed. The cleavage of the 65 kDa form leads to the generation of a linker peptide, and 8 kDa and 50 kDa products. The active form, the 8/50 kDa heterodimer, is resistant to degradation. Complete removal of the linker peptide appears to be a prerequisite to the complete activation of the enzyme.
  • Glycosylation at Asn 162, Asn 178, Asn 200, Asn 217, Asn 238, and Asn 459
  • Modification sites at PhosphoSitePlus

Antibody Products

No data available for DME Specific Peptides for HPSE Gene

Domains & Families for HPSE Gene

Protein Domains for HPSE Gene

Suggested Antigen Peptide Sequences for HPSE Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9Y251

UniProtKB/Swiss-Prot:

HPSE_HUMAN :
  • Belongs to the glycosyl hydrolase 79 family.
Family:
  • Belongs to the glycosyl hydrolase 79 family.
genes like me logo Genes that share domains with HPSE: view

No data available for Gene Families for HPSE Gene

Function for HPSE Gene

Molecular function for HPSE Gene

GENATLAS Biochemistry:
heparanase,widely expressed,noteworthy in placenta,platelet,spleen,smooth muscle cells,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,involved in tumor invasion and metastasis
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
pH dependence: Optimum pH is 4-6. {ECO:0000269 PubMed:10446189, ECO:0000269 PubMed:10764835, ECO:0000269 PubMed:12713442, ECO:0000269 PubMed:15848168};
UniProtKB/Swiss-Prot CatalyticActivity:
Endohydrolysis of (1->4)-beta-D-glycosidic bonds of heparan sulfate chains in heparan sulfate proteoglycan.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by EDTA, laminarin sulfate and, to a lower extent, by heparin and sulfamin and activated by calcium and magnesium.
UniProtKB/Swiss-Prot 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.

Enzyme Numbers (IUBMB) for HPSE Gene

Gene Ontology (GO) - Molecular Function for HPSE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0045545 syndecan binding IDA 15292202
genes like me logo Genes that share ontologies with HPSE: view
genes like me logo Genes that share phenotypes with HPSE: view

Animal Models for HPSE Gene

MGI Knock Outs for HPSE:

Animal Model Products

  • Taconic Biosciences Mouse Models for HPSE

miRNA for HPSE Gene

miRTarBase miRNAs that target HPSE

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for HPSE Gene

Localization for HPSE Gene

Subcellular locations from UniProtKB/Swiss-Prot for HPSE Gene

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}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for HPSE Gene COMPARTMENTS Subcellular localization image for HPSE gene
Compartment Confidence
extracellular 5
lysosome 5
nucleus 5
vacuole 5
golgi apparatus 2
chloroplast 1
cytoskeleton 1
endosome 1
mitochondrion 1
plasma membrane 1

Gene Ontology (GO) - Cellular Components for HPSE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005764 lysosome IDA 15126626
GO:0005765 lysosomal membrane IEA --
genes like me logo Genes that share ontologies with HPSE: view

Pathways & Interactions for HPSE Gene

genes like me logo Genes that share pathways with HPSE: view

Interacting Proteins for HPSE Gene

Gene Ontology (GO) - Biological Process for HPSE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005975 carbohydrate metabolic process IEA,TAS --
GO:0006027 glycosaminoglycan catabolic process TAS --
GO:0007160 cell-matrix adhesion IDA 12773484
GO:0008152 metabolic process IEA --
GO:0010575 positive regulation of vascular endothelial growth factor production IDA 16452201
genes like me logo Genes that share ontologies with HPSE: view

No data available for SIGNOR curated interactions for HPSE Gene

Drugs & Compounds for HPSE Gene

(19) Drugs for HPSE Gene - From: DrugBank, DGIdb, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Heparin Approved, Investigational Pharma Antagonist, cofactor, Enzyme, substrate 761,246
Dalteparin Approved Pharma Enzyme, substrate 283
Thalidomide Approved, Investigational, Withdrawn Pharma Immunomodulatory agent,sedative drug,angiogenesis inhibitor, Immunomodulatory agents, TNF-alpha synthesis inhibitor 1043
Resveratrol Experimental, Investigational Pharma Wee1 kinase inhibtor,potent and ATP-competitive, Others, Cyclooxygenase inhibitor 106
PI-88 Investigational Pharma inhibitor 0

(29) Additional Compounds for HPSE Gene - From: Tocris, Novoseek, and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Water
  • Dihydrogen oxide
  • Steam
7732-18-5
combretastatin a4
117048-59-6
Linomide
84088-42-6

(5) Tocris Compounds for HPSE Gene

Compound Action Cas Number
Combretastatin A4 Antiangiogenic 117048-59-6
Linomide Immunomodulator with antiangiogenic properties 84088-42-6
Resveratrol Cyclooxygenase inhibitor 501-36-0
Thalidomide TNF-alpha synthesis inhibitor 50-35-1
Tranilast Antiallergic; inhibits inflammatory mediator release from mast cells 53902-12-8
genes like me logo Genes that share compounds with HPSE: view

Transcripts for HPSE Gene

Unigene Clusters for HPSE Gene

Heparanase:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for HPSE Gene

No ASD Table

Relevant External Links for HPSE Gene

GeneLoc Exon Structure for
HPSE
ECgene alternative splicing isoforms for
HPSE

Expression for HPSE Gene

mRNA expression in normal human tissues for HPSE Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for HPSE Gene

This gene is overexpressed in Whole Blood (x19.5).

Protein differential expression in normal tissues from HIPED for HPSE Gene

This gene is overexpressed in Platelet (38.9), Peripheral blood mononuclear cells (19.1), and Serum (8.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for HPSE Gene



SOURCE GeneReport for Unigene cluster for HPSE Gene Hs.44227

mRNA Expression by UniProt/SwissProt for HPSE Gene

Q9Y251-HPSE_HUMAN
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 Henles and Huxleys layers of inner the root sheath (IRS) at anagen phase.
genes like me logo Genes that share expression patterns with HPSE: view

Protein tissue co-expression partners for HPSE Gene

Primer Products

In Situ Assay Products

Orthologs for HPSE Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for HPSE Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia HPSE 35
  • 86.32 (n)
  • 80.92 (a)
HPSE 36
  • 79 (a)
OneToOne
dog
(Canis familiaris)
Mammalia HPSE 35
  • 86.54 (n)
  • 83.08 (a)
HPSE 36
  • 81 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Hpse 35
  • 80.37 (n)
  • 78.08 (a)
Hpse 16
Hpse 36
  • 76 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia HPSE 35
  • 99.32 (n)
  • 98.9 (a)
HPSE 36
  • 99 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Hpse 35
  • 79.91 (n)
  • 77.89 (a)
oppossum
(Monodelphis domestica)
Mammalia HPSE 36
  • 61 (a)
OneToOne
chicken
(Gallus gallus)
Aves HPSE 35
  • 62.57 (n)
  • 61.98 (a)
HPSE 36
  • 62 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia HPSE 36
  • 62 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia hpse 35
  • 61.96 (n)
  • 57.46 (a)
zebrafish
(Danio rerio)
Actinopterygii hpse 35
  • 57.03 (n)
  • 54.38 (a)
hpse 36
  • 50 (a)
OneToOne
thale cress
(Arabidopsis thaliana)
eudicotyledons GUS3 35
  • 44.35 (n)
  • 31.67 (a)
rice
(Oryza sativa)
Liliopsida Os06g0179000 35
  • 44.35 (n)
  • 35.04 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 40 (a)
OneToMany
Species with no ortholog for HPSE:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for HPSE Gene

ENSEMBL:
Gene Tree for HPSE (if available)
TreeFam:
Gene Tree for HPSE (if available)

Paralogs for HPSE Gene

Paralogs for HPSE Gene

(1) SIMAP similar genes for HPSE Gene using alignment to 4 proteins:

genes like me logo Genes that share paralogs with HPSE: view

Variants for HPSE Gene

Sequence variations from dbSNP and Humsavar for HPSE Gene

SNP ID Clin Chr 04 pos Sequence Context AA Info Type
VAR_023600 Some hepatocellular carcinoma
VAR_068907 -
rs4328905 -- 83,322,396(+) TAACT(A/G)TTTTT intron-variant
rs4518235 -- 83,295,692(+) GGCAG(A/G)GATGA intron-variant
rs4693077 -- 83,317,630(+) AACCT(A/T)CCATT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for HPSE Gene

Variant ID Type Subtype PubMed ID
nsv526041 CNV Loss 19592680
nsv829992 CNV Loss 17160897
esv2600138 CNV Deletion 19546169
esv2727902 CNV Deletion 23290073
esv2180695 CNV Deletion 18987734
esv2727903 CNV Deletion 23290073
esv4639 CNV Deletion 18987735
esv6001 CNV Loss 19470904
esv2667959 CNV Deletion 23128226
dgv156n6 CNV Loss 16902084
esv1009126 CNV Deletion 20482838
esv2448972 CNV Deletion 19546169
esv1199239 CNV Deletion 17803354

Variation tolerance for HPSE Gene

Residual Variation Intolerance Score: 46.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.85; 48.14% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for HPSE Gene

HapMap Linkage Disequilibrium report
HPSE
Human Gene Mutation Database (HGMD)
HPSE

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HPSE Gene

Disorders for HPSE Gene

MalaCards: The human disease database

(6) MalaCards diseases for HPSE Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
israeli tick typhus
  • israeli spotted fever
urofacial syndrome 1
  • urofacial syndrome
mucosal melanoma
keratocystic odontogenic tumor
  • ktoc
hepatocellular carcinoma
  • hepatocellular carcinoma, somatic
- elite association - COSMIC cancer census association via MalaCards
Search HPSE in MalaCards View complete list of genes associated with diseases

Relevant External Links for HPSE

Genetic Association Database (GAD)
HPSE
Human Genome Epidemiology (HuGE) Navigator
HPSE
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
HPSE
genes like me logo Genes that share disorders with HPSE: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HPSE Gene

Publications for HPSE Gene

  1. Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis. (PMID: 10395325) Vlodavsky I. … Pecker I. (Nat. Med. 1999) 2 3 4 23 67
  2. Heparanase procoagulant effects and inhibition by heparins. (PMID: 20434010) Nadir Y. … Brenner B. (Thromb. Res. 2010) 3 23 25
  3. Heparanase facilitates cell adhesion and spreading by clustering of cell surface heparan sulfate proteoglycans. (PMID: 18545691) Levy-Adam F. … Ilan N. (PLoS ONE 2008) 3 23 25
  4. Heparanase modulates heparinoids anticoagulant activities via non-enzymatic mechanisms. (PMID: 18064313) Katz B.Z. … Preissner K.T. (Thromb. Haemost. 2007) 3 23 25
  5. Epidermal growth factor-induced heparanase nucleolar localization augments DNA topoisomerase I activity in brain metastatic breast cancer. (PMID: 20164500) Zhang L. … Marchetti D. (Mol. Cancer Res. 2010) 3 23

Products for HPSE Gene

Sources for HPSE Gene

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