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Tbio Inactive heparanase-2

Binds heparin and heparan sulfate with high affinity, but lacks heparanase activity. Inhibits HPSE, possibly by competing for its substrates (in vitro).

This gene encodes a heparanase enzyme. The encoded protein is a endoglycosidase that degrades heparin sulfate proteoglycans located on the extracellular matrix and cell surface. This protein may be involved in biological processes involving remodeling of the extracellular matrix including angiogenesis and tumor progression. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

 Comments

Property Summary

NCBI Gene PubMed Count 33
PubMed Score 286.76
PubTator Score 75.31

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (6)

Disease Target Count P-value
psoriasis 6685 3.4e-29
non-inflammatory breast cancer 208 4.3e-07
invasive ductal carcinoma 2950 3.3e-05
Disease Target Count Z-score Confidence
Type 1 diabetes mellitus 104 0.0 1.0
Disease Target Count
Urofacial syndrome 7
Ochoa syndrome 2
Disease Target Count
Urofacial syndrome 1 1

Expression

  Differential Expression (3)

Disease log2 FC p
invasive ductal carcinoma -1.810 3.3e-05
non-inflammatory breast cancer -1.400 4.3e-07
psoriasis -1.100 3.4e-29

Synonym

Accession Q8WWQ2 Q5VUH4 Q5VUH5 Q5VUH6 Q8WWQ1 Q9HB37 Q9HB38 Q9HB39 Hpa2
Symbols UFS
HPA2
HPR2
UFS1

Gene

HPSE2

PANTHER Protein Class (2)

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

 UniProt Keyword (8)

 GO Function (2)

 GO Component (3)

 GO Process (4)

 Compartment GO Term (18)

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 MGI Phenotype (5)

 GWAS Trait (7)

 HCA RNA Cell Line (33)

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Pathway (8)

Gene RIF (22)

PMID Text
26084486 Our findings identified these 2 genes as a novel breast cancer biomarker gene set, which may facilitate the diagnosis and treatment in breast cancer clinical therapies.
25924634 HPSE2 mutations were found in one Urofacial syndrome family but not detected in patients with non-neurogenic neurogenic bladder and severe lower urinary tract dysfunction
25423319 Heparanase 2 is more intensely expressed in the glandular tissue of cancer than in nonneoplastic endometrium; the HPSE2 expression in the stromal tissue is higher in the nonneoplastic controls compared with cancer mainly in the secretory endometrium.
25145936 autonomic neural protein implicated in bladder emptying
24139593 High expression of heparanase-2 is associated significantly with gastric tumor growth and differentiation
23370684 Data indicate that the overexpression of HPSE1 and HPSE2 in the intervertebral degenerated discs suggests a role for these factors in mediating extracellular matrix remodeling in degenerative discs during disease development.
21450525 A large region of marker homozygosity was observed at 10q24, consistent with known autosomal recessive inheritance, family consanguinity and previous genetic mapping in other families with Ochoa syndrome.
21332471 HPSE2 c.631T>C (p.Y211H) is a novel benign SNP and c.1628A>T (p.N543I) is the disease-causing mutation in urofacial syndrome.
21308479 Studies indicate that cathepsin L as the heparanase activating protease.
20560210 Homozygous exonic deletions, nonsense mutations, and frameshift mutations in five further unrelated families confirmed HPSE2 as the causative gene for UFS
20560209 We now report evidence that Heparanse 2 (HPSE2) is the culprit gene for the syndrome. Mutations with a loss of function in the Heparanase 2 (HPSE2) gene
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
20182872 Results demonstrated that the effectors from heparanase peptide-immunized mice could effectively lyse various tumor cells that were heparanase positive and HLA-A*0201 matched.
20031192 These results indicate a regulatory effect of heparanase on TFPI and TFPI-2 in trophoblasts, suggesting a potential involvement of heparanase in early miscarriages.
19955924 Heparanase 2 is involved in neoplastic proliferation, but it was not exclusively associated with the malignant process.
18058084 Data suggest that loss of modified heparan sulphate in the GBM is mediated by an increased heparanase presence and may play a role in the pathogenesis of diabetes-induced proteinuria.
17989358 HPSE plays a role in extracellular matrix remodeling and in increasing heparin-binding growth factor release during embryo implantation.
16879396 Heparanase expression is inversely correlated with survival of nasopharyngeal carcinoma (NPC) patients, indicating heparanase is a reliable prognostic factor, and further supports that heparanase is a valid target for the development of anti-cancer drugs.
16385451 Observational study of gene-disease association. (HuGE Navigator)
15837740 Heparanase expression seems to be involved in the invasiveness and aggressiveness of head and neck squamous cell carcinomas.
15709168 Study demonstrating that increased heparanase expression in prostate cancer tissues is due to promoter hypomethylation and up-regulation of transcription factor EGR1.
15475937 Heparanase may facilitate invasion and metastasis of gastric carcinoma cells.

AA Sequence 

MRVLCAFPEAMPSSNSRPPACLAPGALYLALLLHLSLSSQAGDRRPLPVDRAAGLKEKTLILLDVSTKNP      1 - 70
VRTVNENFLSLQLDPSIIHDGWLDFLSSKRLVTLARGLSPAFLRFGGKRTDFLQFQNLRNPAKSRGGPGP     71 - 140
DYYLKNYEDDIVRSDVALDKQKGCKIAQHPDVMLELQREKAAQMHLVLLKEQFSNTYSNLILTARSLDKL    141 - 210
YNFADCSGLHLIFALNALRRNPNNSWNSSSALSLLKYSASKKYNISWELGNEPNNYRTMHGRAVNGSQLG    211 - 280
KDYIQLKSLLQPIRIYSRASLYGPNIGRPRKNVIALLDGFMKVAGSTVDAVTWQHCYIDGRVVKVMDFLK    281 - 350
TRLLDTLSDQIRKIQKVVNTYTPGKKIWLEGVVTTSAGGTNNLSDSYAAGFLWLNTLGMLANQGIDVVIR    351 - 420
HSFFDHGYNHLVDQNFNPLPDYWLSLLYKRLIGPKVLAVHVAGLQRKPRPGRVIRDKLRIYAHCTNHHNH    421 - 490
NYVRGSITLFIINLHRSRKKIKLAGTLRDKLVHQYLLQPYGQEGLKSKSVQLNGQPLVMVDDGTLPELKP    491 - 560
RPLRAGRTLVIPPVTMGFYVVKNVNALACRYR                                          561 - 592
//

Text Mined References (32)

PMID Year Title
26084486 2015 Gene expression profiling leads to discovery of correlation of matrix metalloproteinase 11 and heparanase 2 in breast cancer progression.
25924634 2015 HPSE2 mutations in urofacial syndrome, non-neurogenic neurogenic bladder and lower urinary tract dysfunction.
25423319 2015 Immunohistochemical expression of heparanases 1 and 2 in benign tissue and in invasive neoplasia of the endometrium: a case-control study.
25145936 2015 Urinary tract effects of HPSE2 mutations.
24554482 2014 Genome-wide association study of peripheral neuropathy with D-drug-containing regimens in AIDS Clinical Trials Group protocol 384.
24139593 2013 High expression of heparanase-2 is an independent prognostic parameter for favorable survival in gastric cancer patients.
23829686 2013 Rank-based genome-wide analysis reveals the association of ryanodine receptor-2 gene variants with childhood asthma among human populations.
23793025 2013 Genome-wide meta-analysis identifies new susceptibility loci for migraine.
23370684 2013 Expression of heparanase isoforms in intervertebral discs classified according to Pfirrmann grading system for disc degeneration.
23251661 2012 Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
21980299 2011 A genome-wide meta-analysis of six type 1 diabetes cohorts identifies multiple associated loci.
21450525 2011 Exome capture and massively parallel sequencing identifies a novel HPSE2 mutation in a Saudi Arabian child with Ochoa (urofacial) syndrome.
21332471 2012 First HPSE2 missense mutation in urofacial syndrome.
21308479 2011 The heparanase system and tumor metastasis: is heparanase the seed and soil?
20576607 2010 Heparanase 2 interacts with heparan sulfate with high affinity and inhibits heparanase activity.
20560210 2010 Mutations in HPSE2 cause urofacial syndrome.
20560209 2010 Loss-of-function mutations in HPSE2 cause the autosomal recessive urofacial syndrome.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20182872 2010 Cytotoxic T lymphocyte epitopes from human heparanase can elicit a potent anti-tumor immune response in mice.
20031192 2010 Involvement of Heparanase in early pregnancy losses.
19955924 2009 Heparanase-2 expression in normal ovarian epithelium and in benign and malignant ovarian tumors.
18617780 2008 Heparanase-2, syndecan-1, and extracellular matrix remodeling in colorectal carcinoma.
18528290 2008 Heparanase-2 and syndecan-1 in colon cancer: the ugly ducklings or the beautiful swans?
17989358 2008 Decidual heparanase activity is increased during pregnancy in the baboon (Papio anubis) and in in vitro decidualization of human stromal cells.
16385451 2006 A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.
15164054 2004 The DNA sequence and comparative analysis of human chromosome 10.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11027606 2000 Cloning and expression profiling of Hpa2, a novel mammalian heparanase family member.
10458906 1999 Construction of a physical and transcript map for a 1-Mb genomic region containing the urofacial (Ochoa) syndrome gene on 10q23-q24 and localization of the disease gene within two overlapping BAC clones (<360 kb).
10360399 1999 Genetic homogeneity, high-resolution mapping, and mutation analysis of the urofacial (Ochoa) syndrome and exclusion of the glutamate oxaloacetate transaminase gene (GOT1) in the critical region as the disease gene.
9199567 1997 Homozygosity and linkage-disequilibrium mapping of the urofacial (Ochoa) syndrome gene to a 1-cM interval on chromosome 10q23-q24.