Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGEPP8V)

DOT Name Inactive heparanase-2 (HPSE2)
Synonyms Hpa2
Gene Name HPSE2
Related Disease
Cervical cancer ( )
Cervical carcinoma ( )
Urofacial syndrome type 1 ( )
Acute coronary syndrome ( )
Acute leukaemia ( )
Acute lymphocytic leukaemia ( )
Acute myelogenous leukaemia ( )
Acute myocardial infarction ( )
Adenocarcinoma ( )
Alzheimer disease ( )
Arterial thrombosis ( )
Breast cancer ( )
Dengue ( )
Dyskeratosis congenita ( )
Haemophilia A ( )
Head and neck carcinoma ( )
Hemophilia ( )
Hepatitis B virus infection ( )
Hepatitis C virus infection ( )
Hydatidiform mole ( )
Hydatidiform mole, recurrent, 1 ( )
Metastatic malignant neoplasm ( )
Migraine disorder ( )
Neoplasm ( )
Plasma cell myeloma ( )
Prostate neoplasm ( )
Small lymphocytic lymphoma ( )
Squamous cell carcinoma ( )
Trichohepatoenteric syndrome ( )
Type-1 diabetes ( )
Uterine fibroids ( )
Ochoa syndrome ( )
Bladder cancer ( )
Coronary atherosclerosis ( )
Coronary heart disease ( )
Glanzmann thrombasthenia ( )
Glaucoma/ocular hypertension ( )
Myelodysplastic syndrome ( )
Ocular hypertension ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
UniProt ID
HPSE2_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF03662
Sequence
MRVLCAFPEAMPSSNSRPPACLAPGALYLALLLHLSLSSQAGDRRPLPVDRAAGLKEKTL
ILLDVSTKNPVRTVNENFLSLQLDPSIIHDGWLDFLSSKRLVTLARGLSPAFLRFGGKRT
DFLQFQNLRNPAKSRGGPGPDYYLKNYEDDIVRSDVALDKQKGCKIAQHPDVMLELQREK
AAQMHLVLLKEQFSNTYSNLILTARSLDKLYNFADCSGLHLIFALNALRRNPNNSWNSSS
ALSLLKYSASKKYNISWELGNEPNNYRTMHGRAVNGSQLGKDYIQLKSLLQPIRIYSRAS
LYGPNIGRPRKNVIALLDGFMKVAGSTVDAVTWQHCYIDGRVVKVMDFLKTRLLDTLSDQ
IRKIQKVVNTYTPGKKIWLEGVVTTSAGGTNNLSDSYAAGFLWLNTLGMLANQGIDVVIR
HSFFDHGYNHLVDQNFNPLPDYWLSLLYKRLIGPKVLAVHVAGLQRKPRPGRVIRDKLRI
YAHCTNHHNHNYVRGSITLFIINLHRSRKKIKLAGTLRDKLVHQYLLQPYGQEGLKSKSV
QLNGQPLVMVDDGTLPELKPRPLRAGRTLVIPPVTMGFYVVKNVNALACRYR
Function Binds heparin and heparan sulfate with high affinity, but lacks heparanase activity. Inhibits HPSE, possibly by competing for its substrates (in vitro).
Tissue Specificity
Widely expressed, with the highest expression in brain, mammary gland, prostate, small intestine, testis and uterus. In the central nervous system, expressed in the spinal chord, caudate nucleus, thalamus, substantia nigra, medulla oblongata, putamen and pons. In the urinary bladder, expressed in longitudinal and circular layers of detrusor muscle. Found both in normal and cancer tissues.
KEGG Pathway
Glycosaminoglycan degradation (hsa00531 )
Metabolic pathways (hsa01100 )
Proteoglycans in cancer (hsa05205 )
Reactome Pathway
HS-GAG degradation (R-HSA-2024096 )

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cervical cancer DISFSHPF Definitive Biomarker [1]
Cervical carcinoma DIST4S00 Definitive Biomarker [1]
Urofacial syndrome type 1 DISDUYJH Definitive Autosomal recessive [2]
Acute coronary syndrome DIS7DYEW Strong Genetic Variation [3]
Acute leukaemia DISDQFDI Strong Posttranslational Modification [4]
Acute lymphocytic leukaemia DISPX75S Strong Genetic Variation [5]
Acute myelogenous leukaemia DISCSPTN Strong Genetic Variation [6]
Acute myocardial infarction DISE3HTG Strong Genetic Variation [3]
Adenocarcinoma DIS3IHTY Strong Biomarker [7]
Alzheimer disease DISF8S70 Strong Altered Expression [8]
Arterial thrombosis DIS2LR4O Strong Genetic Variation [3]
Breast cancer DIS7DPX1 Strong Genetic Variation [9]
Dengue DISKH221 Strong Biomarker [10]
Dyskeratosis congenita DISSXV0K Strong Posttranslational Modification [11]
Haemophilia A DIS0RQ2E Strong Genetic Variation [12]
Head and neck carcinoma DISOU1DS Strong Altered Expression [13]
Hemophilia DIS1S8P6 Strong Genetic Variation [12]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [14]
Hepatitis C virus infection DISQ0M8R Strong Genetic Variation [15]
Hydatidiform mole DISKNP7O Strong Posttranslational Modification [16]
Hydatidiform mole, recurrent, 1 DISXUJWE Strong Posttranslational Modification [16]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [13]
Migraine disorder DISFCQTG Strong Genetic Variation [17]
Neoplasm DISZKGEW Strong Biomarker [1]
Plasma cell myeloma DIS0DFZ0 Strong Genetic Variation [5]
Prostate neoplasm DISHDKGQ Strong Altered Expression [18]
Small lymphocytic lymphoma DIS30POX Strong Biomarker [19]
Squamous cell carcinoma DISQVIFL Strong Altered Expression [20]
Trichohepatoenteric syndrome DISL3ODF Strong Biomarker [21]
Type-1 diabetes DIS7HLUB Strong Genetic Variation [22]
Uterine fibroids DISBZRMJ Strong Genetic Variation [23]
Ochoa syndrome DIS1MDEZ Supportive Autosomal recessive [24]
Bladder cancer DISUHNM0 Limited Genetic Variation [25]
Coronary atherosclerosis DISKNDYU Limited Biomarker [26]
Coronary heart disease DIS5OIP1 Limited Genetic Variation [26]
Glanzmann thrombasthenia DISFGGTG Limited Genetic Variation [27]
Glaucoma/ocular hypertension DISLBXBY Limited Genetic Variation [28]
Myelodysplastic syndrome DISYHNUI Limited Genetic Variation [29]
Ocular hypertension DISC2BT9 Limited Genetic Variation [28]
Urinary bladder cancer DISDV4T7 Limited Genetic Variation [25]
Urinary bladder neoplasm DIS7HACE Limited Genetic Variation [25]
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⏷ Show the Full List of 41 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Inactive heparanase-2 (HPSE2). [30]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Inactive heparanase-2 (HPSE2). [31]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Inactive heparanase-2 (HPSE2). [32]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Inactive heparanase-2 (HPSE2). [33]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the methylation of Inactive heparanase-2 (HPSE2). [34]
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References

1 The immunoexpression of heparanase 2 in normal epithelium, intraepithelial, and invasive squamous neoplasia of the cervix.J Low Genit Tract Dis. 2012 Jul;16(3):256-62. doi: 10.1097/LGT.0b013e3182422c69.
2 Three new European cases of urofacial (Ochoa) syndrome. Clin Dysmorphol. 2001 Jul;10(3):165-70. doi: 10.1097/00019605-200107000-00002.
3 Platelet glycoprotein Ibalpha HPA-2 Met/VNTR B haplotype as a genetic predictor of myocardial infarction and sudden cardiac death.Circulation. 2001 Aug 21;104(8):876-80. doi: 10.1161/hc3301.094907.
4 Genome-wide determination of DNA methylation by Hpa II tiny fragment enrichment by ligation-mediated PCR (HELP) for the study of acute leukemias.Methods Mol Biol. 2009;538:395-407. doi: 10.1007/978-1-59745-418-6_20.
5 Genomic hypomethylation in human chronic lymphocytic leukemia.Blood. 1992 Oct 15;80(8):2074-80.
6 Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
7 Biochemical and cytogenetic studies of human lung cancers.J Thorac Cardiovasc Surg. 1988 Dec;96(6):840-8.
8 Upregulated Expression of Heparanase and Heparanase 2 in the Brains of Alzheimer's Disease.J Alzheimers Dis. 2017;58(1):185-192. doi: 10.3233/JAD-161298.
9 Clonal origins of human breast cancer.J Pathol. 2001 Aug;194(4):406-12. doi: 10.1002/path.937.
10 HLA and other gene associations with dengue disease severity.Curr Top Microbiol Immunol. 2010;338:99-114. doi: 10.1007/978-3-642-02215-9_8.
11 Skewed X-inactivation in carriers of X-linked dyskeratosis congenita.Blood. 1997 Sep 15;90(6):2213-6.
12 Hemophilia B in a female carrier due to skewed inactivation of the normal X-chromosome.Am J Hematol. 1998 May;58(1):72-6. doi: 10.1002/(sici)1096-8652(199805)58:1<72::aid-ajh13>3.0.co;2-7.
13 Heparanase 2 interacts with heparan sulfate with high affinity and inhibits heparanase activity.J Biol Chem. 2010 Sep 3;285(36):28010-9. doi: 10.1074/jbc.M110.116384. Epub 2010 Jun 24.
14 Expression of the hepatitis B virus genome in chronic hepatitis B carriers and patients with hepatocellular carcinoma.Proc Natl Acad Sci U S A. 1987 Feb;84(3):847-50. doi: 10.1073/pnas.84.3.847.
15 Association of human platelet antigens polymorphisms with susceptibility to hepatitis C virus infection in Chinese population.Int J Immunogenet. 2017 Dec;44(6):337-342. doi: 10.1111/iji.12341. Epub 2017 Sep 20.
16 Relative levels of methylation in human growth hormone and chorionic somatomammotropin genes in expressing and non-expressing tissues.Nucleic Acids Res. 1982 Jun 11;10(11):3459-74. doi: 10.1093/nar/10.11.3459.
17 Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine.Nat Genet. 2016 Aug;48(8):856-66. doi: 10.1038/ng.3598. Epub 2016 Jun 20.
18 Increased heparanase expression is caused by promoter hypomethylation and up-regulation of transcriptional factor early growth response-1 in human prostate cancer. Clin Cancer Res. 2005 Feb 1;11(3):1028-36.
19 bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia.Blood. 1993 Sep 15;82(6):1820-8.
20 Heparanase expression at the invasion front of human head and neck cancers and correlation with poor prognosis.Clin Cancer Res. 2005 Apr 15;11(8):2899-906. doi: 10.1158/1078-0432.CCR-04-0664.
21 Loss-of-function mutations in HPSE2 cause the autosomal recessive urofacial syndrome. Am J Hum Genet. 2010 Jun 11;86(6):957-62. doi: 10.1016/j.ajhg.2010.04.016.
22 A genome-wide meta-analysis of six type 1 diabetes cohorts identifies multiple associated loci.PLoS Genet. 2011 Sep;7(9):e1002293. doi: 10.1371/journal.pgen.1002293. Epub 2011 Sep 29.
23 Translation and validation of the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire for the Brazilian Portuguese language.Sao Paulo Med J. 2017 Mar-Apr;135(2):107-115. doi: 10.1590/1516-3180.2016.0223281016. Epub 2017 Mar 13.
24 Urofacial Syndrome. 2013 Aug 22 [updated 2023 Sep 28]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
25 Development and Initial Testing of a Modified UroVysion-Based Fluorescence In Situ Hybridization Score for Prediction of Progression in Bladder Cancer.Am J Clin Pathol. 2020 Jan 2;153(2):274-284. doi: 10.1093/ajcp/aqz165.
26 Polymorphisms of human platelet alloantigens HPA-1 and HPA-2 associated with severe coronary artery disease.Cardiovasc Pathol. 2010 Sep-Oct;19(5):302-7. doi: 10.1016/j.carpath.2009.04.003. Epub 2009 Jun 9.
27 Analysis of platelet membrane glycoprotein polymorphisms in Glanzmann thrombasthenia showed the French gypsy mutation in the alphaIIb gene to be strongly linked to the HPA-1b polymorphism in beta3.J Thromb Haemost. 2003 Mar;1(3):573-5. doi: 10.1046/j.1538-7836.2003.00107.x.
28 The atrial natriuretic peptide gene in patients with familial primary open-angle glaucoma.Biochem Biophys Res Commun. 1996 Jun 14;223(2):221-5. doi: 10.1006/bbrc.1996.0874.
29 Semi-quantitative study of calcitonin gene methylation in myelodysplastic syndrome.Chin Med J (Engl). 1998 Aug;111(8):690-3.
30 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
31 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
32 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
33 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
34 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.