Browse HPSE

Summary
SymbolHPSE
Nameheparanase
Aliases HPA; HSE1; HPSE1; HPA1; HPR11; endo-glucoronidase; heparanase-1
Chromosomal Location4q21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location 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).
Domain PF03662 Glycosyl hydrolase family 79
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 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.

> Gene Ontology
 
Biological Process GO:0001525 angiogenesis
GO:0001819 positive regulation of cytokine production
GO:0001942 hair follicle development
GO:0006022 aminoglycan metabolic process
GO:0006026 aminoglycan catabolic process
GO:0006027 glycosaminoglycan catabolic process
GO:0006029 proteoglycan metabolic process
GO:0006516 glycoprotein catabolic process
GO:0006790 sulfur compound metabolic process
GO:0007160 cell-matrix adhesion
GO:0007596 blood coagulation
GO:0007599 hemostasis
GO:0008544 epidermis development
GO:0009100 glycoprotein metabolic process
GO:0010573 vascular endothelial growth factor production
GO:0010574 regulation of vascular endothelial growth factor production
GO:0010575 positive regulation of vascular endothelial growth factor production
GO:0022404 molting cycle process
GO:0022405 hair cycle process
GO:0030167 proteoglycan catabolic process
GO:0030193 regulation of blood coagulation
GO:0030194 positive regulation of blood coagulation
GO:0030198 extracellular matrix organization
GO:0030200 heparan sulfate proteoglycan catabolic process
GO:0030201 heparan sulfate proteoglycan metabolic process
GO:0030203 glycosaminoglycan metabolic process
GO:0031589 cell-substrate adhesion
GO:0033687 osteoblast proliferation
GO:0033688 regulation of osteoblast proliferation
GO:0033690 positive regulation of osteoblast proliferation
GO:0042303 molting cycle
GO:0042633 hair cycle
GO:0042634 regulation of hair cycle
GO:0042635 positive regulation of hair cycle
GO:0043062 extracellular structure organization
GO:0043491 protein kinase B signaling
GO:0043588 skin development
GO:0044273 sulfur compound catabolic process
GO:0045682 regulation of epidermis development
GO:0045684 positive regulation of epidermis development
GO:0048514 blood vessel morphogenesis
GO:0050817 coagulation
GO:0050818 regulation of coagulation
GO:0050820 positive regulation of coagulation
GO:0050878 regulation of body fluid levels
GO:0051797 regulation of hair follicle development
GO:0051798 positive regulation of hair follicle development
GO:0051896 regulation of protein kinase B signaling
GO:0051897 positive regulation of protein kinase B signaling
GO:0060055 angiogenesis involved in wound healing
GO:0061041 regulation of wound healing
GO:0061042 vascular wound healing
GO:0090303 positive regulation of wound healing
GO:0098773 skin epidermis development
GO:1900046 regulation of hemostasis
GO:1900048 positive regulation of hemostasis
GO:1901136 carbohydrate derivative catabolic process
GO:1901565 organonitrogen compound catabolic process
GO:1903034 regulation of response to wounding
GO:1903036 positive regulation of response to wounding
Molecular Function GO:0001948 glycoprotein binding
GO:0004553 hydrolase activity, hydrolyzing O-glycosyl compounds
GO:0004566 beta-glucuronidase activity
GO:0016798 hydrolase activity, acting on glycosyl bonds
GO:0030305 heparanase activity
GO:0043394 proteoglycan binding
GO:0043395 heparan sulfate proteoglycan binding
GO:0045545 syndecan binding
GO:1901681 sulfur compound binding
Cellular Component GO:0005578 proteinaceous extracellular matrix
GO:0005765 lysosomal membrane
GO:0005775 vacuolar lumen
GO:0043202 lysosomal lumen
GO:0045121 membrane raft
GO:0098589 membrane region
GO:0098852 lytic vacuole membrane
GO:0098857 membrane microdomain
> KEGG and Reactome Pathway
 
KEGG hsa00531 Glycosaminoglycan degradation
hsa01100 Metabolic pathways
Reactome R-HSA-1630316: Glycosaminoglycan metabolism
R-HSA-2024096: HS-GAG degradation
R-HSA-1638091: Heparan sulfate/heparin (HS-GAG) metabolism
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-1430728: Metabolism
R-HSA-71387: Metabolism of carbohydrates
R-HSA-6798695: Neutrophil degranulation
Summary
SymbolHPSE
Nameheparanase
Aliases HPA; HSE1; HPSE1; HPA1; HPR11; endo-glucoronidase; heparanase-1
Chromosomal Location4q21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between HPSE and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between HPSE and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
25849134Breast Carcinoma; NeuroblastomaPromote immunity (T cell function; infiltration)Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes.
18316618Melanoma; Lymphoma; Lung CarcinomaPromote immunity (T cell function); essential for immunotherapyH-2Kb-restricted CTL epitopes from mouse heparanase elicit an antitumor immune response in vivo.
28581441Melanoma; Prostate Carcinoma; Breast CarcinomaPromote immunity (infiltration)However, mice lacking heparanase specifically in NK cells (Hpsefl/fl NKp46-iCre mice) were highly tumor prone when challenged with the carcinogen methylcholanthrene (MCA). Cytokine and immune checkpoint blockade immunotherapy for metastases was compromised when NK cells lacked heparanase. NK cell invasion of primary tumors and recruitment to the site of metastasis were strictly dependent on the presence of heparanase.
Summary
SymbolHPSE
Nameheparanase
Aliases HPA; HSE1; HPSE1; HPA1; HPR11; endo-glucoronidase; heparanase-1
Chromosomal Location4q21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of HPSE in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolHPSE
Nameheparanase
Aliases HPA; HSE1; HPSE1; HPA1; HPR11; endo-glucoronidase; heparanase-1
Chromosomal Location4q21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of HPSE in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.0020.997
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.2960.762
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.2290.734
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.3790.307
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.2410.818
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.5580.671
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1910.638
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.5330.614
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.2540.838
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.2210.0915
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.0720.37
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.1720.313
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of HPSE in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277302.7-2.71
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275903.4-3.41
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.811.8-70.577
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.516.7-4.21
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59200200.357
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38275.305.30.507
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.206.21
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolHPSE
Nameheparanase
Aliases HPA; HSE1; HPSE1; HPA1; HPR11; endo-glucoronidase; heparanase-1
Chromosomal Location4q21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of HPSE. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolHPSE
Nameheparanase
Aliases HPA; HSE1; HPSE1; HPA1; HPR11; endo-glucoronidase; heparanase-1
Chromosomal Location4q21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of HPSE. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HPSE.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolHPSE
Nameheparanase
Aliases HPA; HSE1; HPSE1; HPA1; HPR11; endo-glucoronidase; heparanase-1
Chromosomal Location4q21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of HPSE. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolHPSE
Nameheparanase
Aliases HPA; HSE1; HPSE1; HPA1; HPR11; endo-glucoronidase; heparanase-1
Chromosomal Location4q21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of HPSE expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolHPSE
Nameheparanase
Aliases HPA; HSE1; HPSE1; HPA1; HPR11; endo-glucoronidase; heparanase-1
Chromosomal Location4q21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between HPSE and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolHPSE
Nameheparanase
Aliases HPA; HSE1; HPSE1; HPA1; HPR11; endo-glucoronidase; heparanase-1
Chromosomal Location4q21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting HPSE collected from DrugBank database.
> Drugs from DrugBank database
 

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