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Gene Review

ITGB3  -  integrin, beta 3 (platelet glycoprotein...

Homo sapiens

Synonyms: BDPLT16, BDPLT2, CD61, GP3A, GPIIIa, ...
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Disease relevance of ITGB3


Psychiatry related information on ITGB3

  • Evaluation of a CD61 MoAb method for enumeration of platelets in thrombocytopenic patients and its impact on the transfusion decision-making process [6].

High impact information on ITGB3

  • To test the in vivo effectiveness of the IgM antiidiotype, thrombocytopenia was induced in mice with 25 microgram of affinity-purified anti-GPIIIa 49-66 (mouse GPIIIa has 83% homology with human GPIIIa and Fc receptors for human IgG1) [7].
  • The recombinant His327 form of GPIIb was found to be fully capable of associating with GPIIIa, therefore the role of the calcium-binding domains in intersubunit association was further examined by constructing amino-terminal segments of GPIIb that ended before the first, second, and third calcium-binding domains [8].
  • A point mutation (C to T) was localized in exon D (iv) of GPIIIa that resulted in an 214Arg to 214Trp amino acid substitution [9].
  • It thus appears that amino acid 143 of GPIIIa is not only associated with Pen phenotype, but specifically controls the formation and expression of the Pen alloantigenic determinants [10].
  • Interestingly, this polymorphic residue is located within the putative RGD binding site (residues 109-171) of GPIIIa [10].

Chemical compound and disease context of ITGB3


Biological context of ITGB3

  • Furthermore, the serotonin QTL on 17q that was identified previously in this population, integrin beta 3 (ITGB3), and a novel locus on 2q influence serotonin levels only in males, whereas linkage to a region on chromosome 6q is specific to females [16].
  • METHODS AND MEASUREMENTS: We genotyped and performed association tests on 19 single nucleotide polymorphisms in ITGB3 in the Hutterites, a founder population, and in three outbred replication populations [17].
  • Because both the Leu33Pro polymorphism and the serotonin system have been implicated in cardiovascular disease (CVD) risk and treatment response, we studied additional variation in ITGB3 and its relationship to intermediate phenotypes associated with CVD in the same population [1].
  • We also show preliminary evidence that genotypes at the ITGB3 and SLC6A4 loci may interact to affect autism susceptibility (P=0.033) [18].
  • The integrin beta3 (ITGB3) and serotonin transporter (SLC6A4) genes were both recently identified as male quantitative trait loci (QTLs) for serotonin levels and alleles of each have been associated with autism [18].

Anatomical context of ITGB3

  • This physical proximity of GPIIb and GPIIIa may be involved in the concurrent expression of these proteins by megakaryocytes, and may result in linkage disequilibrium between these two genes, which would limit the use of restriction length polymorphisms in linkage studies of GPIIb/IIIa abnormalities in small kindreds [19].
  • This indicates that the GPIIIa-containing heterodimers in platelets and endothelial cells are not identical structures, but are members of a subfamily within the human family of adhesion protein receptors sharing an identical beta subunit [2].
  • Human mast cells derived from fetal liver cells cultured with stem cell factor express a functional CD51/CD61 (alpha v beta 3) integrin [20].
  • Changes in the percentage of CD61- or CD62P-positive leukocytes were significantly greater during hemodialysis with RC than with PS [21].
  • Immunohistochemical staining after exposure to PMA showed that the expression of the platelet-associated markers CD41 and CD61 was enhanced in all cell lines indicating possible differentiation along the megakaryocyte lineage [22].

Associations of ITGB3 with chemical compounds

  • We therefore evaluated the integrin-beta3 gene (ITGB3), an integrin gene within an asthma linkage peak on chromosome 17, as a candidate for susceptibility to asthma- and atopy-related phenotypes [17].
  • Variation in ITGB3 is associated with asthma and sensitization to mold allergen in four populations [17].
  • CD markedly inhibited the assembly of the cytoskeletal core as well as GPIIIa retention, whereas MB resulted in a large Triton-insoluble residue which contained GPIIIa [23].
  • This study was designed to determine the structure of the gene for glycoprotein (GP) GPIIIa, the beta-subunit of the platelet membrane GPIIb-IIIa complex [3].
  • These included (i) the transmembrane spanning segment, (ii) the cytoplasmic region containing the potential phosphorylation sites, and (iii) the six domains in the NH2-terminal half of GPIIIa that are highly conserved between two other integrin beta-subunits [3].

Physical interactions of ITGB3

  • There is evidence that fibrinogen itself binds to regions in the amino terminal portions of both GPIIb and GPIIIa and that the sites interacting with the fibrinogen gamma chain and with RGD-containing peptides are spatially distinct [24].
  • The HEL GPIIIa sequence was compared with the sequences of the beta subunit for the human LFA-1/Mac-1/p150.95 complex and human endothelial cell GPIIIa, revealing a 38% similarity with the former and virtual identity with the latter [2].
  • A novel homozygous mutation (1619delC) in GPIIb gene associated with Glanzmann thrombasthenia, the decay of GPIIb-mRNA and the synthesis of a truncated GPIIb unable to form complex with GPIIIa [25].
  • Since neither neuraminidase- nor endoglycopeptidase F-treatment of GPIIIa had any significant effect on the binding of PSG3, this array must be located within the amino acid sequence of GPIIIa but not in the carbohydrate moiety [26].

Regulatory relationships of ITGB3

  • Anti-ITGAV/ITGB3 antibodies significantly reduced the size of the capillary network (P < 0.05) on Matrigel and also suppressed TNF-induced apoptosis (P < 0.05) in TCL1 cells [27].
  • In this study we investigated mechanisms of platelet interaction with von Willebrand factor (vWF) induced by activating anti-glycoprotein (GP)IIb-IIIa antibody CRC54 directed against LIBS (ligand-induced binding site epitope) in GPIIIa [28].
  • The expression of CD61 did not alter during storage and the percentage of platelets expressing CD42b was > 88% in all units on day 7 [29].
  • To determine how this mutation impaired GPIIb-IIIa expression, recombinant GPIIb containing the mutation was coexpressed with GPIIIa in COS-1 cells [30].
  • The platelet population was specified by the antiglycoprotein IIIa (CD61) antibody and activated platelets by the anti-P selectin (CD62) antibody [31].

Other interactions of ITGB3


Analytical, diagnostic and therapeutic context of ITGB3

  • To study the association between early fetal loss and the presence of the PLA2 polymorphism of the ITGB3 gene we conducted a case-control study on 98 cases (i.e., women in fertile age, who experienced at least one episode of early fetal loss) and 38 healthy controls [35].
  • In particular, the strongest effect of the ITGB3 PL(A2) allele was expressed on the risk of occlusion after revascularization procedures, mainly after stent implantation, a condition in which platelet activation is more important as compared with other stenotic mechanisms [36].
  • The radiation hybrid panel indicates that the most likely position of human CDC27 on human chromosomes 17 is between the marker D17S409 and the beta 3 subunit of integrin (ITGB3) [37].
  • Northern blot analysis using RNA from both HEL and endothelial cells revealed two GPIIIa transcripts of 5.9 and 4.1 kb [2].
  • Immunoprecipitation of radiolabeled platelets using polyclonal anti-FXIII A-chain antibody identified two proteins corresponding to GPIIb and GPIIIa [38].


  1. Variation in ITGB3 has sex-specific associations with plasma lipoprotein(a) and whole blood serotonin levels in a population-based sample. Weiss, L.A., Abney, M., Parry, R., Scanu, A.M., Cook, E.H., Ober, C. Hum. Genet. (2005) [Pubmed]
  2. Structure of platelet glycoprotein IIIa. A common subunit for two different membrane receptors. Zimrin, A.B., Eisman, R., Vilaire, G., Schwartz, E., Bennett, J.S., Poncz, M. J. Clin. Invest. (1988) [Pubmed]
  3. Characterization of the human platelet glycoprotein IIIa gene. Comparison with the fibronectin receptor beta-subunit gene. Lanza, F., Kieffer, N., Phillips, D.R., Fitzgerald, L.A. J. Biol. Chem. (1990) [Pubmed]
  4. Different levels of platelet activation in preeclamptic, normotensive pregnant, and nonpregnant women. Holthe, M.R., Staff, A.C., Berge, L.N., Lyberg, T. Am. J. Obstet. Gynecol. (2004) [Pubmed]
  5. Relationship between the expression levels of CD61, CD63, and PAC-1 on platelet surface in peripheral blood and the transplanted kidney function. Zhang, Y., Guan, D.L., Xia, C.Q., Han, Z.Y., Xu, J.J., Gao, J.Z., Wu, K.R., Zhang, Y.G., Guan, D. Transplant. Proc. (2003) [Pubmed]
  6. Evaluation of a CD61 MoAb method for enumeration of platelets in thrombocytopenic patients and its impact on the transfusion decision-making process. Arroyo, J.L., García-Marcos, M.A., López, A., Menéndez, P., Tabernero, M.D., Sánchez-Abarca, L.I., Avila-Zarza, C., San Miguel, J.F., Orfao, A. Transfusion (2001) [Pubmed]
  7. Antiidiotype antibody against platelet anti-GPIIIa contributes to the regulation of thrombocytopenia in HIV-1-ITP patients. Nardi, M., Karpatkin, S. J. Exp. Med. (2000) [Pubmed]
  8. Glanzmann thrombasthenia resulting from a single amino acid substitution between the second and third calcium-binding domains of GPIIb. Role of the GPIIb amino terminus in integrin subunit association. Wilcox, D.A., Paddock, C.M., Lyman, S., Gill, J.C., Newman, P.J. J. Clin. Invest. (1995) [Pubmed]
  9. A new variant of Glanzmann's thrombasthenia (Strasbourg I). Platelets with functionally defective glycoprotein IIb-IIIa complexes and a glycoprotein IIIa 214Arg----214Trp mutation. Lanza, F., Stierlé, A., Fournier, D., Morales, M., André, G., Nurden, A.T., Cazenave, J.P. J. Clin. Invest. (1992) [Pubmed]
  10. An amino acid polymorphism within the RGD binding domain of platelet membrane glycoprotein IIIa is responsible for the formation of the Pena/Penb alloantigen system. Wang, R., Furihata, K., McFarland, J.G., Friedman, K., Aster, R.H., Newman, P.J. J. Clin. Invest. (1992) [Pubmed]
  11. Integrin alpha-2 and beta-3 gene polymorphisms and breast cancer risk. Langsenlehner, U., Renner, W., Yazdani-Biuki, B., Eder, T., Wascher, T.C., Paulweber, B., Clar, H., Hofmann, G., Samonigg, H., Krippl, P. Breast Cancer Res. Treat. (2006) [Pubmed]
  12. Amino acid 489 is encoded by a mutational "hot spot" on the beta 3 integrin chain: the CA/TU human platelet alloantigen system. Wang, R., McFarland, J.G., Kekomaki, R., Newman, P.J. Blood (1993) [Pubmed]
  13. The disulfide-rich region of platelet glycoprotein (GP) IIIa contains hydrophilic peptide sequences that bind anti-GPIIIa autoantibodies from patients with immune thrombocytopenic purpura (ITP). Beardsley, D.J., Tang, C., Chen, B.G., Lamborn, C., Gomes, E., Srimatkandada, V. Biophys. Chem. (2003) [Pubmed]
  14. Evolution of bone marrow fibrosis and stromal antigenic expression in chronic myeloid leukemia on alpha interferon and Ara-C therapy. Straetmans, N., Ma, D.D., Nevell, D.F., Arthur, C. Hematopathology and molecular hematology. (1996) [Pubmed]
  15. A human monoclonal antibody specific for the leucine-33 (P1A1, HPA-1a) form of platelet glycoprotein IIIa from a V gene phage display library. Griffin, H.M., Ouwehand, W.H. Blood (1995) [Pubmed]
  16. Sex-specific genetic architecture of whole blood serotonin levels. Weiss, L.A., Abney, M., Cook, E.H., Ober, C. Am. J. Hum. Genet. (2005) [Pubmed]
  17. Variation in ITGB3 is associated with asthma and sensitization to mold allergen in four populations. Weiss, L.A., Lester, L.A., Gern, J.E., Wolf, R.L., Parry, R., Lemanske, R.F., Solway, J., Ober, C. Am. J. Respir. Crit. Care Med. (2005) [Pubmed]
  18. ITGB3 shows genetic and expression interaction with SLC6A4. Weiss, L.A., Ober, C., Cook, E.H. Hum. Genet. (2006) [Pubmed]
  19. Chromosomal localization of the genes for the vitronectin and fibronectin receptors alpha subunits and for platelet glycoproteins IIb and IIIa. Sosnoski, D.M., Emanuel, B.S., Hawkins, A.L., van Tuinen, P., Ledbetter, D.H., Nussbaum, R.L., Kaos, F.T., Schwartz, E., Phillips, D., Bennett, J.S. J. Clin. Invest. (1988) [Pubmed]
  20. Human mast cells derived from fetal liver cells cultured with stem cell factor express a functional CD51/CD61 (alpha v beta 3) integrin. Shimizu, Y., Irani, A.M., Brown, E.J., Ashman, L.K., Schwartz, L.B. Blood (1995) [Pubmed]
  21. Platelet GPIIb/IIIa is activated and platelet-leukocyte coaggregates formed in vivo during hemodialysis. Kawabata, K., Nakai, S., Miwa, M., Sugiura, T., Otsuka, Y., Shinzato, T., Hiki, Y., Tomimatsu, I., Ushida, Y., Hosono, F., Maeda, K. Nephron (2002) [Pubmed]
  22. Differential platelet-associated factor gene expression by a panel of human cell lines with megakaryoblastic properties after treatment with phorbol myristate acetate. Micallef, M., Matsuo, Y., Takayama, K., Ariyasu, T., Otani, T., Minowada, J. Hematological oncology. (1994) [Pubmed]
  23. Assembly and GPIIIa content of cytoskeletal core in platelets agglutinated with bovine von Willebrand factor. Puszkin, E.G., Mauss, E.A., Zucker, M.B. Blood (1990) [Pubmed]
  24. Platelet-fibrinogen interactions. Bennett, J.S. Ann. N. Y. Acad. Sci. (2001) [Pubmed]
  25. A novel homozygous mutation (1619delC) in GPIIb gene associated with Glanzmann thrombasthenia, the decay of GPIIb-mRNA and the synthesis of a truncated GPIIb unable to form complex with GPIIIa. Losonczy, G., Rosenberg, N., Kiss, C., Kappelmayer, J., Vereb, G., Kerényi, A., Balogh, I., Muszbek, L. Thromb. Haemost. (2005) [Pubmed]
  26. Specific cross-reaction of IgG anti-phospholipid antibody with platelet glycoprotein IIIa. Tokita, S., Arai, M., Yamamoto, N., Katagiri, Y., Tanoue, K., Igarashi, K., Umeda, M., Inoue, K. Thromb. Haemost. (1996) [Pubmed]
  27. Tumor necrosis factor and vascular endothelial growth factor induce endothelial integrin repertories, regulating endovascular differentiation and apoptosis in a human extravillous trophoblast cell line. Fukushima, K., Miyamoto, S., Tsukimori, K., Kobayashi, H., Seki, H., Takeda, S., Kensuke, E., Ohtani, K., Shibuya, M., Nakano, H. Biol. Reprod. (2005) [Pubmed]
  28. Von Willebrand factor can support platelet aggregation via interaction with activated GPIIb-IIIa and GPIb. Naimushin, Y.A., Mazurov, A.V. Platelets (2004) [Pubmed]
  29. In vitro function of platelet concentrates prepared after filtration of whole blood or buffy coat pools. Turner, C.P., Sutherland, J., Wadhwa, M., Dilger, P., Cardigan, R. Vox Sang. (2005) [Pubmed]
  30. Glanzmann thrombasthenia secondary to a Gly273-->Asp mutation adjacent to the first calcium-binding domain of platelet glycoprotein IIb. Poncz, M., Rifat, S., Coller, B.S., Newman, P.J., Shattil, S.J., Parrella, T., Fortina, P., Bennett, J.S. J. Clin. Invest. (1994) [Pubmed]
  31. Placental insufficiency is characterized by platelet activation in the fetus. Trudinger, B., Song, J.Z., Wu, Z.H., Wang, J. Obstetrics and gynecology. (2003) [Pubmed]
  32. Independent modulation of von Willebrand factor and fibrinogen binding to the platelet membrane glycoprotein IIb/IIIa complex as demonstrated by monoclonal antibody. Lombardo, V.T., Hodson, E., Roberts, J.R., Kunicki, T.J., Zimmerman, T.S., Ruggeri, Z.M. J. Clin. Invest. (1985) [Pubmed]
  33. The GPIIB-IIIa-like complex may function as a human melanoma cell adhesion receptor for thrombospondin. Tuszynski, G.P., Karczewski, J., Smith, L., Murphy, A., Rothman, V.L., Knudsen, K.A. Exp. Cell Res. (1989) [Pubmed]
  34. Effects of 2,3,7,8-TCDD and PCB 126 on human thymic epithelial cells in vitro. Riecke, K., Schmidt, A., Stahlmann, R. Arch. Toxicol. (2003) [Pubmed]
  35. Association of PLA2 polymorphism of the ITGB3 gene with early fetal loss. Ruzzi, L., Ciarafoni, I., Silvestri, L., Semeraro, M.L., Abeni, D. Fertil. Steril. (2005) [Pubmed]
  36. Platelet glycoprotein IIb/IIIa polymorphism and coronary artery disease: implications for clinical practice. Di Castelnuovo, A., de Gaetano, G., Benedetta Donati, M., Iacoviello, L. American journal of pharmacogenomics : genomics-related research in drug development and clinical practice. (2005) [Pubmed]
  37. Localization of the human homolog of the yeast cell division control 27 gene (CDC27) proximal to ITGB3 on human chromosome 17q21.3. Ho, P.P., Couch, F.J., Brody, L.C., Abel, K.J., Boehnke, M., Shearon, T.H., Chandrasekharappa, S.C., Collins, F.S., Weber, B.L. Somat. Cell Mol. Genet. (1995) [Pubmed]
  38. Factor XIIIa binding to activated platelets is mediated through activation of glycoprotein IIb-IIIa. Cox, A.D., Devine, D.V. Blood (1994) [Pubmed]
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