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Gene Review

HPSE2  -  heparanase 2 (inactive)

Homo sapiens

Synonyms: HPA2, HPR2, Hpa2, Inactive heparanase-2, UFS, ...
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Disease relevance of HPSE2


High impact information on HPSE2

  • Previously, we have established that an antigenic polymorphism of platelets, the HPA-2 or Ko alloantigen system, is located on the 45-kD amino-terminal globular domain of GPIb alpha [6].
  • DNA-typing for the HPA-2 alloantigen system on genomic DNA obtained from a small number of cells may be applied for determining the genotype of a fetus from an immunized mother or of severely thrombocytopenic patients [6].
  • NH2-terminal globular domain of human platelet glycoprotein Ib alpha has a methionine 145/threonine145 amino acid polymorphism, which is associated with the HPA-2 (Ko) alloantigens [6].
  • Restriction fragment length polymorphism analysis of the amplified DNA of 3 HPA-2(a-,b+), 2 HPA-2(a+,b+), and 11 HPA-2(a+,b-) donors showed that these restriction sites were associated with the HPA-2 alleles [6].
  • Our data are compatible with an involvement of the leucine-rich repeat domain of GPIbalpha in vWF binding and indicate that recombinant GPIbalpha may be used to detect HPA-2 antibodies [2].

Chemical compound and disease context of HPSE2


Biological context of HPSE2


Anatomical context of HPSE2

  • A larger study is required, however, to determine whether HPA-2 is a novel risk factor for branch retinal vein occlusion [13].
  • From the sequences of the two HPR cDNAs, the HPR1 protein, but not the HPR2 protein, was found to have a targeting sequence into peroxisomes at the carboxy terminus [14].

Regulatory relationships of HPSE2


Other interactions of HPSE2

  • Cloning and expression profiling of Hpa2, a novel mammalian heparanase family member [8].
  • We studied haplotypes of ITGA2 defined by single nucleotide substitutions at positions -52, 807, and 1648, and GP1BA variants defined by sequence changes in positions -5 (Kozak), 1018 (T145M, HPA-2) and 1285 (VNTR A, B, C and D) [16].
  • CONCLUSIONS: Our results indicate that the HPA-1, HPA-2, HPA-3, and HPA-5 polymorphisms are not associated with an increased risk for stroke [17].
  • Only two antigenic polymorphisms have thus far been established in these proteins: the HPA-2 in GP Ib alpha and the rare Iy variant in GP Ib beta [18].

Analytical, diagnostic and therapeutic context of HPSE2

  • Sequence analyses predict that all three Hpa2 proteins are intracellular, membrane-bound enzymes [8].
  • Prolactin was measured in 472 patients 1 day before (Hpr1) and in 457 patients 10 days after (Hpr2) mastectomy [19].
  • The purpose of present study was to investigate the association between gene polymorphism of GP I balpha (human platelet antigen 2, HPA2) and ischemic stroke in a matched case-control study [20].
  • MATERIALS AND METHODS: Using allele-specific restriction enzyme analysis, we studied the distribution of HPA-1 and HPA-2 alleles in six Brazilian Amazon tribes of Amerindians, belonging to five different language stocks [21].
  • Genotyping for GP I balpha polymorphism was documented by polymerase chain reaction amplification and restriction enzyme analysis.There were no statistically significant differences in the GP I balpha HPA2 genotype distribution between ischemic stroke group, large-vessel subtype group, small-vessel subtype group and corresponding control groups [20].


  1. Localization of the platelet-specific HPA-2 (Ko) alloantigens on the N-terminal globular fragment of platelet glycoprotein Ib alpha. Kuijpers, R.W., Ouwehand, W.H., Bleeker, P.M., Christie, D., von dem Borne, A.E. Blood (1992) [Pubmed]
  2. Threonine-145/methionine-145 variants of baculovirus produced recombinant ligand binding domain of GPIbalpha express HPA-2 epitopes and show equal binding of von Willebrand factor. Li, C.Q., Garner, S.F., Davies, J., Smethurst, P.A., Wardell, M.R., Ouwehand, W.H. Blood (2000) [Pubmed]
  3. Stepwise cloning and molecular characterization of the HgiDI restriction-modification system from Herpetosiphon giganteus Hpa2. Düsterhöft, A., Erdmann, D., Kröger, M. Nucleic Acids Res. (1991) [Pubmed]
  4. A common polymorphism flanking the ATG initiator codon of GPIb alpha does not affect expression and is not a major risk factor for arterial thrombosis. Corral, J., Lozano, M.L., González-Conejero, R., Martínez, C., Iniesta, J.A., Rivera, J., Vicente, V. Thromb. Haemost. (2000) [Pubmed]
  5. Alloimmunization against human platelet antigen 2 (HPA2) in a series of multi-transfused beta-thalassemia patients. Tazzari, P.L., Ricci, F., Tassi, C., Bontadini, A., Fruet, F., Conte, R. Haematologica (1998) [Pubmed]
  6. NH2-terminal globular domain of human platelet glycoprotein Ib alpha has a methionine 145/threonine145 amino acid polymorphism, which is associated with the HPA-2 (Ko) alloantigens. Kuijpers, R.W., Faber, N.M., Cuypers, H.T., Ouwehand, W.H., von dem Borne, A.E. J. Clin. Invest. (1992) [Pubmed]
  7. Glycoprotein Ib polymorphisms influence platelet plug formation under high shear rates. Jilma-Stohlawetz, P., Homoncik, M., Jilma, B., Knechtelsdorfer, M., Unger, P., Mannhalter, C., Santoso, S., Panzer, S. Br. J. Haematol. (2003) [Pubmed]
  8. Cloning and expression profiling of Hpa2, a novel mammalian heparanase family member. McKenzie, E., Tyson, K., Stamps, A., Smith, P., Turner, P., Barry, R., Hircock, M., Patel, S., Barry, E., Stubberfield, C., Terrett, J., Page, M. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  9. Polymorphisms of platelet membrane glycoprotein Ib associated with arterial thrombotic disease. Gonzalez-Conejero, R., Lozano, M.L., Rivera, J., Corral, J., Iniesta, J.A., Moraleda, J.M., Vicente, V. Blood (1998) [Pubmed]
  10. Determination of human platelet antigen frequencies in the Dutch population by immunophenotyping and DNA (allele-specific restriction enzyme) analysis. Simsek, S., Faber, N.M., Bleeker, P.M., Vlekke, A.B., Huiskes, E., Goldschmeding, R., von dem Borne, A.E. Blood (1993) [Pubmed]
  11. The largest variant of platelet glycoprotein Ib alpha has four tandem repeats of 13 amino acids in the macroglycopeptide region and a genetic linkage with methionine145. Ishida, F., Furihata, K., Ishida, K., Yan, J., Kitano, K., Kiyosawa, K., Furuta, S. Blood (1995) [Pubmed]
  12. Pumpkin hydroxypyruvate reductases with and without a putative C-terminal signal for targeting to microbodies may be produced by alternative splicing. Hayashi, M., Tsugeki, R., Kondo, M., Mori, H., Nishimura, M. Plant Mol. Biol. (1996) [Pubmed]
  13. Role of five platelet membrane glycoprotein polymorphisms in branch retinal vein occlusion. Salomon, O., Moisseiev, J., Vilganski, T., Dardik, R., Kurtz, S., Shpringer, E., Steinberg, D.M., Rosenberg, N. Blood Coagul. Fibrinolysis (2006) [Pubmed]
  14. A leaf-peroxisomal protein, hydroxypyruvate reductase, is produced by light-regulated alternative splicing. Mano, S., Hayashi, M., Nishimura, M. Cell Biochem. Biophys. (2000) [Pubmed]
  15. von Willebrand factor but not alpha-thrombin binding to platelet glycoprotein Ibalpha is influenced by the HPA-2 polymorphism. Ulrichts, H., Vanhoorelbeke, K., Cauwenberghs, S., Vauterin, S., Kroll, H., Santoso, S., Deckmyn, H. Arterioscler. Thromb. Vasc. Biol. (2003) [Pubmed]
  16. Platelet glycoprotein I(b)alpha and integrin alpha2 beta1 polymorphisms: gene frequencies and linkage disequilibrium in a population diversity panel. Di Paola, J., Jugessur, A., Goldman, T., Reiland, J., Tallman, D., Sayago, C., Murray, J.C. J. Thromb. Haemost. (2005) [Pubmed]
  17. Polymorphisms of the human platelet antigens HPA-1, HPA-2, HPA-3, and HPA-5 on the platelet receptors for fibrinogen (GPIIb/IIIa), von Willebrand factor (GPIb/IX), and collagen (GPIa/IIa) are not correlated with an increased risk for stroke. Carlsson, L.E., Greinacher, A., Spitzer, C., Walther, R., Kessler, C. Stroke (1997) [Pubmed]
  18. Genetic polymorphism in human platelet glycoprotein GP Ib/IX/V complex is enriched in GP V (CD42d). Koskela, S., Kekomäki, R., Partanen, J. Tissue Antigens (1998) [Pubmed]
  19. Serum prolactin levels and their relationship to survival in women with operable breast cancer. Wang, D.Y., Stepniewska, K.A., Allen, D.S., Fentiman, I.S., Bulbrook, R.D., Kwa, H.G., De Stavola, B.L., Reed, M.J. Journal of clinical epidemiology. (1995) [Pubmed]
  20. Gene polymorphism of platelet glycoprotein I balpha in Chinese patients with large- and small-artery subtypes of ischemic stroke. Gao, X.G., Huo, Y., Liu, X.Z., Teng, Z.P. Eur. Neurol. (2005) [Pubmed]
  21. Gene frequencies of the HPA-1 and HPA-2 platelet antigen alleles among the Amerindians. Covas, D.T., Delgado, M., Zeitune, M.M., Guerreiro, J.F., Santos, S.E., Zago, M.A. Vox Sang. (1997) [Pubmed]
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