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Gene Review

ITGA2  -  integrin, alpha 2 (CD49B, alpha 2 subunit...

Homo sapiens

Synonyms: BR, CD49 antigen-like family member B, CD49B, CD49b, Collagen receptor, ...
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Disease relevance of ITGA2


High impact information on ITGA2

  • Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat color in mice [6].
  • Integrin alpha 2 beta 1 (VLA-2) mediates reorganization and contraction of collagen matrices by human cells [7].
  • Here we report the cloning and expression of a second human natriuretic peptide-receptor guanylate cyclase, the ANP-B receptor [8].
  • In separate studies, the 'very late antigens' VLA-1 (Mr 210K/130K) and VLA-2 (Mr 160K/130K) were initially characterized as surface heterodimers appearing 2-4 weeks after in vitro stimulation of human T cells [9].
  • RD rhabdomyosarcoma cells expressed little VLA-2, did not bind to 35S-labeled virus, and resisted infection until transfected with complementary DNA encoding the alpha 2 subunit of VLA-2 [10].

Chemical compound and disease context of ITGA2

  • Our results suggest that VLA-2 integrin is involved in metastasis of RCC and that poorly differentiated tumor cells have a different integrin phenotype when compared to normal or highly differentiated tumor cells [3].
  • Infection by SA-dependent or SA-independent rotavirus strains was 2- to 10-fold more productive in VLA-2-expressing CHO cells than in parental CHO cells, and the increased susceptibility to infection was blocked with anti-VLA-2 antibody [11].
  • In non-neoplastic breast tissue and in fibroadenomas VLA-2 and VLA-3 were expressed by myoepithelial cells and on the basolateral surface of the luminal cells [12].
  • Hypercholesterolemia and hypoalphalipoproteinemia (low HDL cholesterol levels) are apparently no major risk factors for SHL, whereas the GPIa C807T polymorphism, elevated fibrinogen levels, and smoking are associated with an increased risk for SHL [13].
  • METHODS: One hundred fifty-eight patients with chronic renal insufficiency [mean serum creatinine +/- SD = 2.7 +/- 1.0 mg/dL (242. 3 to +/- 92.8 micromol/L)] and undergoing cardiac angiography were randomized to receive either a mixed endothelin A and B receptor antagonist, SB 290670, or placebo [14].

Biological context of ITGA2


Anatomical context of ITGA2

  • Studies with alpha-subunit (CD49)-specific mAbs indicated that the integrins VLA-4 and -5 mediated migration across FN-preincubated filters, and VLA-2, -4, -5, and -6 were involved in eosinophil migration through filters covered with HUVEC [20].
  • As assessed by inhibition of adhesion using mAb to the VLA-2, -3, -4, -5, and -6, NK cell adhesion to fibronectin was mediated by VLA-4 and 5, and their adhesion to laminin by VLA-3 and -6 [21].
  • VLA proteins such as VLA-4, VLA-3, or VLA-2, which are found involved in cell-cell contacts, could contribute to the promotion of T-cell activation by facilitating adherence between LC and T cells [22].
  • Both in normal and EB specimens MoAb against VLA-2, VLA-3, and VNR alpha determinants showed reactivity with the total cytoplasmic membrane of basal keratinocytes and basement membrane zone [23].
  • VLA-1, VLA-2 and VLA-3 were present in glandular epithelium, stromal cells and vessels of both groups [24].

Associations of ITGA2 with chemical compounds

  • VLA-2 (also called gpIa/IIa on platelets) is a collagen receptor with a unique alpha subunit and a beta subunit common to other adhesion receptors in the VLA/integrin family [16].
  • Further, the anti-GPIa antibody (Gi9) inhibited liposome adhesion more than GUR83-35 at all shear rates tested [25].
  • After contact with polyethylene terephthalate, a slight but significant decrease in the percentage of both CD29 and CD49e positive cells was observed, which suggests a lower number of cells expressing the fibronectin receptor alpha5beta1 [26].
  • PATIENTS AND METHODS: The glycoprotein alpha(IIb)beta3 (GPIIb/IIIa) is the main fibrinogen receptor on platelets, with GPIb-IX-V and GPIa/IIa being the von Willebrand Factor and collagen receptors, respectively [27].
  • CONCLUSIONS: In vivo selection and flow cytometric analysis revealed that Lea, sLea, CD49b, CD49c, and CD29 appear to be involved in the increase of metastatic activity [28].

Physical interactions of ITGA2

  • These data support a model wherein collagen can directly interact with GPIa/IIa and can indirectly interact with GPIIb/IIIa via intermediary adhesive proteins [29].
  • The VLA-2 complex (alpha 2/beta 1) was found to act as collagen receptor on platelets and the VLA-6 complex (alpha 6/beta 1) as laminin receptor [30].
  • Absolute values for lifetime and anisotropy were lower for the CCK-8 probe bound to the type B receptor than for this probe bound to the type A receptor, and Alexa fluorescence was more easily quenched by iodide at the type B receptor [31].

Regulatory relationships of ITGA2


Other interactions of ITGA2

  • IL-6 induced expression of CD49b (alpha-chain of VLA-2, 20% +/- 11 vs 2% +/- 1) and CD49c (alpha-chain of VLA-3, 43% +/- 17 vs 5% +/- 3), which are not expressed on resting NK cells [21].
  • Using a panel of specific antibodies we showed that freshly harvested human epidermal basal cells express VLA-2 and VLA-3 receptors, a low amount of VLA-5, but fail to express VLA-4 [35].
  • These results show that PltGPs HPA-1, 2 and 5 or the C807T dimorphism of GPIa do not influence the clinical expressivity of VWD type 1 [17].
  • Moreover, a significant increase in the mean channel for CD49b and for the vitronectin receptor CD51/CD61 was observed [26].
  • Our results show that only VLA-2, VLA-3, LFA-3, and the VLA-alpha 6 subunit are expressed on the epithelium [36].

Analytical, diagnostic and therapeutic context of ITGA2

  • To analyze the role of ITGA2 and ITGB3 polymorphisms for breast cancer risk and prognosis, we performed a case-control study including 500 female breast cancer patients and 500 healthy female age-matched control subjects [5].
  • To define the polymorphism responsible for the Br alloantigen system platelet RNA PCR technique, was used to amplify GPIa mRNA transcripts [37].
  • Immunoprecipitation with specific monoclonal antibodies identified the complexes as very late activation antigen (VLA)-1 (alpha 1 beta 1) and VLA-2 (alpha 2 beta 1), respectively [38].
  • Localization of the Br polymorphism on a 144 bp exon of the GPIa gene and its application in platelet DNA typing [39].
  • A de novo expression of VLA-1, VLA-2, and VLA-4 as detected by immunocytochemistry occurred in resistant Caki-1 cells [40].


  1. 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]
  2. Correlation of very late activation integrin and CD44 expression with extrarenal invasion and metastasis of renal cell carcinomas. Gilcrease, M.Z., Truong, L., Brown, R.W. Hum. Pathol. (1996) [Pubmed]
  3. In vivo distribution of integrins in renal cell carcinoma: integrin-phenotype alteration in different degrees of tumor differentiation and VLA-2 involvement in tumor metastasis. Anastassiou, G., Duensing, S., Steinhoff, G., Kirchner, H., Ganser, A., Atzpodien, J. Cancer Biother. (1995) [Pubmed]
  4. Role of membrane glycoproteins in the interaction of blood platelets with the vessel wall--the study on platelet adhesion to in vitro cultured subendothelial matrix. Kawai, Y., Handa, M., Nagai, H., Kamata, T., Anbo, H., Kawano, K., Araki, Y., Yamamoto, M., Ikeda, Y., Watanabe, K. Nippon Ketsueki Gakkai Zasshi (1989) [Pubmed]
  5. 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]
  6. Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat color in mice. Hosoda, K., Hammer, R.E., Richardson, J.A., Baynash, A.G., Cheung, J.C., Giaid, A., Yanagisawa, M. Cell (1994) [Pubmed]
  7. Integrin alpha 2 beta 1 (VLA-2) mediates reorganization and contraction of collagen matrices by human cells. Schiro, J.A., Chan, B.M., Roswit, W.T., Kassner, P.D., Pentland, A.P., Hemler, M.E., Eisen, A.Z., Kupper, T.S. Cell (1991) [Pubmed]
  8. Differential activation by atrial and brain natriuretic peptides of two different receptor guanylate cyclases. Chang, M.S., Lowe, D.G., Lewis, M., Hellmiss, R., Chen, E., Goeddel, D.V. Nature (1989) [Pubmed]
  9. Fibronectin receptor structures in the VLA family of heterodimers. Takada, Y., Huang, C., Hemler, M.E. Nature (1987) [Pubmed]
  10. Identification of the integrin VLA-2 as a receptor for echovirus 1. Bergelson, J.M., Shepley, M.P., Chan, B.M., Hemler, M.E., Finberg, R.W. Science (1992) [Pubmed]
  11. VLA-2 (alpha2beta1) integrin promotes rotavirus entry into cells but is not necessary for rotavirus attachment. Ciarlet, M., Crawford, S.E., Cheng, E., Blutt, S.E., Rice, D.A., Bergelson, J.M., Estes, M.K. J. Virol. (2002) [Pubmed]
  12. Low expression of beta 1, alpha 2 and alpha 3 subunits of VLA integrins in malignant mammary tumours. Pignatelli, M., Hanby, A.M., Stamp, G.W. J. Pathol. (1991) [Pubmed]
  13. Vascular risk factors in sudden hearing loss. Rudack, C., Langer, C., Stoll, W., Rust, S., Walter, M. Thromb. Haemost. (2006) [Pubmed]
  14. Exacerbation of radiocontrast nephrotoxicity by endothelin receptor antagonism. Wang, A., Holcslaw, T., Bashore, T.M., Freed, M.I., Miller, D., Rudnick, M.R., Szerlip, H., Thames, M.D., Davidson, C.J., Shusterman, N., Schwab, S.J. Kidney Int. (2000) [Pubmed]
  15. An association of candidate gene haplotypes and bleeding severity in von Willebrand disease (VWD) type 1 pedigrees. Kunicki, T.J., Federici, A.B., Salomon, D.R., Koziol, J.A., Head, S.R., Mondala, T.S., Chismar, J.D., Baronciani, L., Canciani, M.T., Peake, I.R. Blood (2004) [Pubmed]
  16. The primary structure of the VLA-2/collagen receptor alpha 2 subunit (platelet GPIa): homology to other integrins and the presence of a possible collagen-binding domain. Takada, Y., Hemler, M.E. J. Cell Biol. (1989) [Pubmed]
  17. Platelet membrane glycoprotein polymorphisms do not influence the clinical expressivity of von Willebrand disease type 1. Pereira, J., Quiroga, T., Pereira, M.E., Morales, M., Goycoolea, M., Hidalgo, P., Prieto, C., Mezzano, D. Thromb. Haemost. (2003) [Pubmed]
  18. Role of cell-cell communication in inhibiting butyric acid-induced T-cell apoptosis. Kurita-Ochiai, T., Seto, S., Ochiai, K. Infect. Immun. (2004) [Pubmed]
  19. Extracellular matrix receptors and the differentiation of human megakaryocytes in vitro. Molla, A., Mossuz, P., Berthier, R. Leuk. Lymphoma (1999) [Pubmed]
  20. Freezing adhesion molecules in a state of high-avidity binding blocks eosinophil migration. Kuijpers, T.W., Mul, E.P., Blom, M., Kovach, N.L., Gaeta, F.C., Tollefson, V., Elices, M.J., Harlan, J.M. J. Exp. Med. (1993) [Pubmed]
  21. Response of human NK cells to IL-6 alterations of the cell surface phenotype, adhesion to fibronectin and laminin, and tumor necrosis factor-alpha/beta secretion. Rabinowich, H., Sedlmayr, P., Herberman, R.B., Whiteside, T.L. J. Immunol. (1993) [Pubmed]
  22. Human epidermal Langerhans cells express integrins of the beta 1 subfamily. Le Varlet, B., Dezutter-Dambuyant, C., Staquet, M.J., Delorme, P., Schmitt, D. J. Invest. Dermatol. (1991) [Pubmed]
  23. Expression of integrins in junctional and dystrophic epidermolysis bullosa. Nazzaro, V., Berti, E., Cerri, A., Brusasco, A., Cavalli, R., Caputo, R. J. Invest. Dermatol. (1990) [Pubmed]
  24. Beta-1 integrin cell adhesion molecules in the endometrium of fertile and infertile women. Klentzeris, L.D., Bulmer, J.N., Trejdosiewicz, L.K., Morrison, L., Cooke, I.D. Hum. Reprod. (1993) [Pubmed]
  25. Reconstitution of adhesive properties of human platelets in liposomes carrying both recombinant glycoproteins Ia/IIa and Ib alpha under flow conditions: specific synergy of receptor-ligand interactions. Nishiya, T., Kainoh, M., Murata, M., Handa, M., Ikeda, Y. Blood (2002) [Pubmed]
  26. Evaluation of endothelial cell integrins after in \ vitro contact with polyethylene terephthalate. Cenni, E., Granchi, D., Verri, E., Remiddi, G., Cavedagna, D., Di Leo, A. Journal of materials science. Materials in medicine. (2001) [Pubmed]
  27. Genetic variation in platelet integrin alphabeta (GPIIb/IIIa) and the metastatic potential of renal cell carcinoma. Kallio, J.P., Mikkelsson, J., Tammela, T.L., Karhunen, P.J., Kellokumpu-Lehtinen, P. BJU Int. (2006) [Pubmed]
  28. Enhancement of metastatic activity of colon cancer as influenced by expression of cell surface antigens. Okazaki, K., Nakayama, Y., Shibao, K., Hirata, K., Nagata, N., Itoh, H. J. Surg. Res. (1998) [Pubmed]
  29. Collagen-platelet interactions: evidence for a direct interaction of collagen with platelet GPIa/IIa and an indirect interaction with platelet GPIIb/IIIa mediated by adhesive proteins. Coller, B.S., Beer, J.H., Scudder, L.E., Steinberg, M.H. Blood (1989) [Pubmed]
  30. Expression of VLA-alpha 2, VLA-alpha 6, and VLA-beta 1 chains in normal mucosa and adenomas of the colon, and in colon carcinomas and their liver metastases. Koretz, K., Schlag, P., Boumsell, L., Möller, P. Am. J. Pathol. (1991) [Pubmed]
  31. Distinct molecular mechanisms for agonist peptide binding to types A and B cholecystokinin receptors demonstrated using fluorescence spectroscopy. Harikumar, K.G., Clain, J., Pinon, D.I., Dong, M., Miller, L.J. J. Biol. Chem. (2005) [Pubmed]
  32. Expression and function of fibronectin receptors on peripheral mononuclear cells in IgA nephropathy. Namie, S., Ozono, Y., Harada, T., Hara, K. Nephrol. Dial. Transplant. (1995) [Pubmed]
  33. Endothelin-1 potentiates human smooth muscle cell growth to PDGF: effects of ETA and ETB receptor blockade. Yang, Z., Krasnici, N., Lüscher, T.F. Circulation (1999) [Pubmed]
  34. VLA-1: a T cell surface antigen which defines a novel late stage of human T cell activation. Hemler, M.E., Jacobson, J.G., Brenner, M.B., Mann, D., Strominger, J.L. Eur. J. Immunol. (1985) [Pubmed]
  35. Identification of specific human epithelial cell integrin receptors as VLA proteins. Staquet, M.J., Levarlet, B., Dezutter-Dambuyant, C., Schmitt, D., Thivolet, J. Exp. Cell Res. (1990) [Pubmed]
  36. Adhesion molecules in normal human conjunctiva. An immunohistological study using monoclonal antibodies. Vorkauf, M., Duncker, G., Nölle, B., Sterry, W. Graefes Arch. Clin. Exp. Ophthalmol. (1993) [Pubmed]
  37. The human platelet alloantigens Br(a) and Brb are associated with a single amino acid polymorphism on glycoprotein Ia (integrin subunit alpha 2). Santoso, S., Kalb, R., Walka, M., Kiefel, V., Mueller-Eckhardt, C., Newman, P.J. J. Clin. Invest. (1993) [Pubmed]
  38. Identification of integrin collagen receptors on human melanoma cells. Kramer, R.H., Marks, N. J. Biol. Chem. (1989) [Pubmed]
  39. Localization of the Br polymorphism on a 144 bp exon of the GPIa gene and its application in platelet DNA typing. Kalb, R., Santoso, S., Unkelbach, K., Kiefel, V., Mueller-Eckhardt, C. Thromb. Haemost. (1994) [Pubmed]
  40. Altered expression of beta 1 integrins in renal carcinoma cell lines exposed to vinblastine. Meyer, N., Duensing, S., Anastassiou, G., Brevis Nunez, F., Grosse, J., Ganser, A., Atzpodien, J. Anticancer Res. (1999) [Pubmed]
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