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Gene Review

ANXA2  -  annexin A2

Homo sapiens

Synonyms: ANX2, ANX2L4, Annexin A2, Annexin II, Annexin-2, ...
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Disease relevance of ANXA2

  • Here, we report that annexin II, a surface phospholipid-binding protein and one of the proposed causes of the hemorrhagic complications of acute promyelocytic leukemia (APL), is also implicated in t(17;19)+ ALL [1].
  • Taken together, our results indicate that the annexin II tetramer can serve as a binding protein for procathepsin B on the surface of tumor cells, an interaction that may facilitate tumor invasion and metastasis [2].
  • Cathepsin B and the annexin II tetramer were shown by immunofluorescent staining to colocalize on the surface of human breast carcinoma and glioma cells [2].
  • Annexin II is also overexpressed in some tumors (5/13). u-PAR is overexpressed in most tumor samples examined (14/15), while u-PA is weakly detected in a low number of cases (3/14); both u-PAR and u-PA are overexpressed in areas of tumor associated pancreatitis [3].
  • A number of studies have suggested that the anionic phospholipid (anPL)-binding protein annexin II may play a role in cytomegalovirus (CMV) infection [4].

High impact information on ANXA2


Chemical compound and disease context of ANXA2


Biological context of ANXA2


Anatomical context of ANXA2


Associations of ANXA2 with chemical compounds


Physical interactions of ANXA2

  • To identify components that could regulate differentially the release of pro- and antithrombogenic factors, we analyzed the contribution of Rab3D and the annexin A2/S100A10 complex, proteins implicated in exocytotic events in other systems [15].
  • Contrary to previous reports, the phospholipid-associated annexin A2 subunit failed to bind t-PA or plasminogen but bound plasmin (Kd = 0.78 microm) [14].
  • Annexin II heterotetramer (AIIt) is a Ca(2+)- and phospholipid-binding protein that consists of two copies of a p36 and p11 subunit [19].
  • Using affinity chromatography, PAGE, MALDI-TOF MS and post source decay, annexin II and beta/gamma actin were identified as proteins specifically bound to PP13/galectin-13 in placenta and fetal hepatic cells [20].
  • Cell surface complex of cathepsin B/annexin II tetramer in malignant progression [21].

Regulatory relationships of ANXA2


Other interactions of ANXA2


Analytical, diagnostic and therapeutic context of ANXA2

  • Monocytes express the annexin A2 heterotetramer on the cell surface as shown by flow cytometry, fluorescence microscopy, and coimmunoprecipitation of biotinylated cell surface proteins [13].
  • Chemical cross-linking experiments with biotinylated annexin II and intact PSV10 cells identified a 55-kDa band on Western blot analysis that reacted with both an anti-p11 antibody and streptavidin but not anti-p36 antibody [28].
  • Our results from surface plasmon resonance analysis showed that A2t and annexin A2 has modest selectivity for PtdIns(4,5)P2 over other phosphoinositides, which is conferred by conserved basic residues, including Lys279 and Lys281, on the convex surface of annexin A2 [29].
  • RESULTS: The only gene for which significant expression differences were detected in both DD analysis and quantitative RT-PCR was lipocortin II (annexin II) (exacerbation > remission, p < 0.05) [30].
  • Western blot analysis under treatment conditions showed that both ATRA and As(2)O(3) markedly decreased the production of annexin II, reaching a level near the baseline at 5 and 7 days after treatment, respectively [31].


  1. Regulation of annexin II by cytokine-initiated signaling pathways and E2A-HLF oncoprotein. Matsunaga, T., Inaba, T., Matsui, H., Okuya, M., Miyajima, A., Inukai, T., Funabiki, T., Endo, M., Look, A.T., Kurosawa, H. Blood (2004) [Pubmed]
  2. Human procathepsin B interacts with the annexin II tetramer on the surface of tumor cells. Mai, J., Finley, R.L., Waisman, D.M., Sloane, B.F. J. Biol. Chem. (2000) [Pubmed]
  3. The plasminogen activator system in pancreas cancer: role of t-PA in the invasive potential in vitro. Paciucci, R., Torà, M., Díaz, V.M., Real, F.X. Oncogene (1998) [Pubmed]
  4. Annexin II enhances cytomegalovirus binding and fusion to phospholipid membranes. Raynor, C.M., Wright, J.F., Waisman, D.M., Pryzdial, E.L. Biochemistry (1999) [Pubmed]
  5. PTEN-Mediated Apical Segregation of Phosphoinositides Controls Epithelial Morphogenesis through Cdc42. Martin-Belmonte, F., Gassama, A., Datta, A., Yu, W., Rescher, U., Gerke, V., Mostov, K. Cell (2007) [Pubmed]
  6. Annexin II and bleeding in acute promyelocytic leukemia. Menell, J.S., Cesarman, G.M., Jacovina, A.T., McLaughlin, M.A., Lev, E.A., Hajjar, K.A. N. Engl. J. Med. (1999) [Pubmed]
  7. Cloning and identification of annexin II as an autocrine/paracrine factor that increases osteoclast formation and bone resorption. Takahashi, S., Reddy, S.V., Chirgwin, J.M., Devlin, R., Haipek, C., Anderson, J., Roodman, G.D. J. Biol. Chem. (1994) [Pubmed]
  8. Signaling-induced association of a tyrosine-phosphorylated 36-kDa protein with p50csk. Ford, C.E., Furlong, M.T., Geahlen, R.L., Harrison, M.L. J. Biol. Chem. (1994) [Pubmed]
  9. Angiogenesis-associated protein annexin II in breast cancer: Selective expression in invasive breast cancer and contribution to tumor invasion and progression. Sharma, M.R., Koltowski, L., Ownbey, R.T., Tuszynski, G.P., Sharma, M.C. Exp. Mol. Pathol. (2006) [Pubmed]
  10. Secretory leukocyte protease inhibitor binds to annexin II, a cofactor for macrophage HIV-1 infection. Ma, G., Greenwell-Wild, T., Lei, K., Jin, W., Swisher, J., Hardegen, N., Wild, C.T., Wahl, S.M. J. Exp. Med. (2004) [Pubmed]
  11. Direct interaction between human cytomegalovirus glycoprotein B and cellular annexin II. Pietropaolo, R.L., Compton, T. J. Virol. (1997) [Pubmed]
  12. Annexin A2 is a novel RNA-binding protein. Filipenko, N.R., MacLeod, T.J., Yoon, C.S., Waisman, D.M. J. Biol. Chem. (2004) [Pubmed]
  13. Identification of the annexin A2 heterotetramer as a receptor for the plasmin-induced signaling in human peripheral monocytes. Laumonnier, Y., Syrovets, T., Burysek, L., Simmet, T. Blood (2006) [Pubmed]
  14. Phospholipid-associated annexin A2-S100A10 heterotetramer and its subunits: characterization of the interaction with tissue plasminogen activator, plasminogen, and plasmin. MacLeod, T.J., Kwon, M., Filipenko, N.R., Waisman, D.M. J. Biol. Chem. (2003) [Pubmed]
  15. Rab3D and annexin A2 play a role in regulated secretion of vWF, but not tPA, from endothelial cells. Knop, M., Aareskjold, E., Bode, G., Gerke, V. EMBO J. (2004) [Pubmed]
  16. Annexin II mediates plasminogen-dependent matrix invasion by human monocytes: enhanced expression by macrophages. Brownstein, C., Deora, A.B., Jacovina, A.T., Weintraub, R., Gertler, M., Khan, K.M., Falcone, D.J., Hajjar, K.A. Blood (2004) [Pubmed]
  17. New insights into the tPA-annexin A2 interaction. Is annexin A2 CYS8 the sole requirement for this association? Roda, O., Valero, M.L., Peiró, S., Andreu, D., Real, F.X., Navarro, P. J. Biol. Chem. (2003) [Pubmed]
  18. Tyrosine phosphorylation of annexin A2 regulates Rho-mediated actin rearrangement and cell adhesion. Rescher, U., Ludwig, C., Konietzko, V., Kharitonenkov, A., Gerke, V. J. Cell. Sci. (2008) [Pubmed]
  19. Identification of annexin II heterotetramer as a plasmin reductase. Kwon, M., Caplan, J.F., Filipenko, N.R., Choi, K.S., Fitzpatrick, S.L., Zhang, L., Waisman, D.M. J. Biol. Chem. (2002) [Pubmed]
  20. Functional analyses of placental protein 13/galectin-13. Than, N.G., Pick, E., Bellyei, S., Szigeti, A., Burger, O., Berente, Z., Janaky, T., Boronkai, A., Kliman, H., Meiri, H., Bohn, H., Than, G.N., Sumegi, B. Eur. J. Biochem. (2004) [Pubmed]
  21. Cell surface complex of cathepsin B/annexin II tetramer in malignant progression. Mai, J., Waisman, D.M., Sloane, B.F. Biochim. Biophys. Acta (2000) [Pubmed]
  22. Metastasis-associated protein S100A4 induces angiogenesis through interaction with Annexin II and accelerated plasmin formation. Semov, A., Moreno, M.J., Onichtchenko, A., Abulrob, A., Ball, M., Ekiel, I., Pietrzynski, G., Stanimirovic, D., Alakhov, V. J. Biol. Chem. (2005) [Pubmed]
  23. S100A10, annexin A2, and annexin a2 heterotetramer as candidate plasminogen receptors. Kwon, M., MacLeod, T.J., Zhang, Y., Waisman, D.M. Front. Biosci. (2005) [Pubmed]
  24. Annexin II stimulates RANKL expression through MAPK. Li, F., Chung, H., Reddy, S.V., Lu, G., Kurihara, N., Zhao, A.Z., Roodman, G.D. J. Bone Miner. Res. (2005) [Pubmed]
  25. The role of p21ras in CD28 signal transduction: triggering of CD28 with antibodies, but not the ligand B7-1, activates p21ras. Nunès, J.A., Collette, Y., Truneh, A., Olive, D., Cantrell, D.A. J. Exp. Med. (1994) [Pubmed]
  26. Cloning and expression of cDNA for human endonexin II, a Ca2+ and phospholipid binding protein. Kaplan, R., Jaye, M., Burgess, W.H., Schlaepfer, D.D., Haigler, H.T. J. Biol. Chem. (1988) [Pubmed]
  27. CD44 and annexin A2 mediate the C5a chemotactic cofactor function of the vitamin D binding protein. McVoy, L.A., Kew, R.R. J. Immunol. (2005) [Pubmed]
  28. Cloning and Characterization of the Annexin II Receptor on Human Marrow Stromal Cells. Lu, G., Maeda, H., Reddy, S.V., Kurihara, N., Leach, R., Anderson, J.L., Roodman, G.D. J. Biol. Chem. (2006) [Pubmed]
  29. Phosphoinositide specificity of and mechanism of lipid domain formation by annexin A2-p11 heterotetramer. Gokhale, N.A., Abraham, A., Digman, M.A., Gratton, E., Cho, W. J. Biol. Chem. (2005) [Pubmed]
  30. Analysis of gene expressions of T cells from children with acute exacerbations of asthma. Katsunuma, T., Kawahara, H., Suda, T., Ishii, T., Ohya, Y., Akasawa, A., Saito, H., Oshida, T., Sugita, Y. Int. Arch. Allergy Immunol. (2004) [Pubmed]
  31. Arsenic trioxide, retinoic acid and Ara-c regulated the expression of annexin II on the surface of APL cells, a novel co-receptor for plasminogen/tissue plasminogen activator. Zhang, X., Zhou, H., Wang, J., Yang, L., Hu, Y., Shen, G., Guo, P., Qiao, Z., Song, S. Thromb. Res. (2002) [Pubmed]
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