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Gene Review

EEA1  -  early endosome antigen 1

Homo sapiens

Synonyms: Early endosome antigen 1, Endosome-associated protein p162, MST105, MSTP105, ZFYVE2, ...
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Disease relevance of EEA1


High impact information on EEA1

  • We propose a novel mechanism whereby oligomeric EEA1 and NSF mediate the local activation of syntaxin 13 upon membrane tethering and, by analogy with viral fusion proteins, coordinate the assembly of a fusion pore [6].
  • Syntaxin 13, the t-SNARE required for endosome fusion, is transiently incorporated into the large oligomers via direct interactions with EEA1 [6].
  • Rab5 and other associated proteins seem to act upstream of EEA1, implying that Rab5 effectors comprise both regulatory molecules and mechanical components of the membrane transport machinery [7].
  • We further show that EEA1 mediates endosome docking and, together with SNAREs, leads to membrane fusion [7].
  • Perforin also triggers the rapid endocytosis of granzymes into large EEA-1-staining vesicles [8].

Biological context of EEA1


Anatomical context of EEA1


Associations of EEA1 with chemical compounds


Physical interactions of EEA1

  • The ProF protein partially co-localizes with EEA1 on vesicular structures and binds to the protein kinases Akt and PKCzeta/lambda (protein kinase Czeta/lambda) via its WD-repeat propeller [20].

Co-localisations of EEA1

  • Washout of forskolin induced retrieval of AQP2 into the cytoplasm, and AQP2 was transiently colocalized with EEA1-positive endosomes [18].
  • Confocal immunofluorescence microscopy of transfected HEp2 cells revealed that the C-terminal part (residues 1277-1411) of EEA1 colocalizes extensively with a GTPase-deficient mutant of the early endosomal GTPase Rab5, while deletion of the FYVE finger or mutations that interfere with zinc binding cause a cytosolic localization [21].
  • STAMP2 also localizes to vesicular-tubular structures in the cytosol and colocalizes with the Early Endosome Antigen1 (EEA1) suggesting that it may be involved in the secretory/endocytic pathways [22].
  • STAMP1 also localizes to vesicular tubular structures in the cytosol and colocalizes with the early endosome antigen 1 (EEA1), suggesting that it may be involved in the secretory/endocytic pathways [23].

Regulatory relationships of EEA1


Other interactions of EEA1

  • Ten minutes after internalization at 37C, Y992- and Y1173-phosphorylated EGFR were almost exclusively located in early endosomes, as shown by co-localization with EEA1 [28].
  • After the translocation to the plasma membrane, AQP2 was endocytosed to EEA1-positive early endosomes, and then transferred back to the original Rab11-positive compartment [19].
  • Therefore, SNX5 is localized to a subdomain of the early endosome distinct from EEA1 and, following EGF stimulation and elevation of PtdIns3,4P2, is also transiently recruited to the plasma membrane [29].
  • By contrast, depletion of RabGAP-5 results in increased endosome size, more endosome-associated EEA1, and disrupts the trafficking of EGF and LAMP1 [30].
  • Furthermore, although both EEA1 and Rabenosyn-5 are required for early endosomal fusion, only overexpression of Rabenosyn-5 inhibits cathepsin D processing, suggesting that the two proteins play distinct roles in endosomal trafficking [31].

Analytical, diagnostic and therapeutic context of EEA1


  1. Rab5 and Rab7, but not ARF6, govern the early events of HIV-1 infection in polarized human placental cells. Vidricaire, G., Tremblay, M.J. J. Immunol. (2005) [Pubmed]
  2. Phosphoinositides and phagocytosis. Gillooly, D.J., Simonsen, A., Stenmark, H. J. Cell Biol. (2001) [Pubmed]
  3. Autoantibodies to early endosome antigen (EEA1) produce a staining pattern resembling cytoplasmic anti-neutrophil cytoplasmic antibodies (C-ANCA). Selak, S., Woodman, R.C., Fritzler, M.J. Clin. Exp. Immunol. (2000) [Pubmed]
  4. Autoantibodies to a novel early endosome antigen 1. Waite, R.L., Sentry, J.W., Stenmark, H., Toh, B.H. Clin. Immunol. Immunopathol. (1998) [Pubmed]
  5. Localization of cellubrevin-related peptide, endobrevin, in the early endosome in pancreatic beta cells and its physiological function in exo-endocytosis of secretory granules. Nagamatsu, S., Nakamichi, Y., Watanabe, T., Matsushima, S., Yamaguchi, S., Ni, J., Itagaki, E., Ishida, H. J. Cell. Sci. (2001) [Pubmed]
  6. Oligomeric complexes link Rab5 effectors with NSF and drive membrane fusion via interactions between EEA1 and syntaxin 13. McBride, H.M., Rybin, V., Murphy, C., Giner, A., Teasdale, R., Zerial, M. Cell (1999) [Pubmed]
  7. The Rab5 effector EEA1 is a core component of endosome docking. Christoforidis, S., McBride, H.M., Burgoyne, R.D., Zerial, M. Nature (1999) [Pubmed]
  8. Perforin triggers a plasma membrane-repair response that facilitates CTL induction of apoptosis. Keefe, D., Shi, L., Feske, S., Massol, R., Navarro, F., Kirchhausen, T., Lieberman, J. Immunity (2005) [Pubmed]
  9. Phosphorylation of EEA1 by p38 MAP kinase regulates mu opioid receptor endocytosis. Macé, G., Miaczynska, M., Zerial, M., Nebreda, A.R. EMBO J. (2005) [Pubmed]
  10. The endosome fusion regulator early-endosomal autoantigen 1 (EEA1) is a dimer. Callaghan, J., Simonsen, A., Gaullier, J.M., Toh, B.H., Stenmark, H. Biochem. J. (1999) [Pubmed]
  11. Characterization of early endosome antigen 1 in neural tissues. Selak, S., Braun, J.E., Fritzler, M.J. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  12. p38 MAP kinase mediates stress-induced internalization of EGFR: implications for cancer chemotherapy. Zwang, Y., Yarden, Y. EMBO J. (2006) [Pubmed]
  13. Epidermal growth factor and membrane trafficking. EGF receptor activation of endocytosis requires Rab5a. Barbieri, M.A., Roberts, R.L., Gumusboga, A., Highfield, H., Alvarez-Dominguez, C., Wells, A., Stahl, P.D. J. Cell Biol. (2000) [Pubmed]
  14. Induction of p38 mitogen-activated protein kinase reduces early endosome autoantigen 1 (EEA1) recruitment to phagosomal membranes. Fratti, R.A., Chua, J., Deretic, V. J. Biol. Chem. (2003) [Pubmed]
  15. Selective membrane recruitment of EEA1 suggests a role in directional transport of clathrin-coated vesicles to early endosomes. Rubino, M., Miaczynska, M., Lippé, R., Zerial, M. J. Biol. Chem. (2000) [Pubmed]
  16. Phosphatidylinositol 3-phosphate recognition by the FYVE domain. Kutateladze, T.G., Ogburn, K.D., Watson, W.T., de Beer, T., Emr, S.D., Burd, C.G., Overduin, M. Mol. Cell (1999) [Pubmed]
  17. Interaction of the EEA1 FYVE finger with phosphatidylinositol 3-phosphate and early endosomes. Role of conserved residues. Gaullier, J.M., Ronning, E., Gillooly, D.J., Stenmark, H. J. Biol. Chem. (2000) [Pubmed]
  18. Aquaporin-2 is retrieved to the apical storage compartment via early endosomes and phosphatidylinositol 3-kinase-dependent pathway. Tajika, Y., Matsuzaki, T., Suzuki, T., Aoki, T., Hagiwara, H., Kuwahara, M., Sasaki, S., Takata, K. Endocrinology (2004) [Pubmed]
  19. Differential regulation of AQP2 trafficking in endosomes by microtubules and actin filaments. Tajika, Y., Matsuzaki, T., Suzuki, T., Ablimit, A., Aoki, T., Hagiwara, H., Kuwahara, M., Sasaki, S., Takata, K. Histochem. Cell Biol. (2005) [Pubmed]
  20. A WD-FYVE protein binds to the kinases Akt and PKCzeta/lambda. Fritzius, T., Burkard, G., Haas, E., Heinrich, J., Schweneker, M., Bosse, M., Zimmermann, S., Frey, A.D., Caelers, A., Bachmann, A.S., Moelling, K. Biochem. J. (2006) [Pubmed]
  21. Endosomal localization of the autoantigen EEA1 is mediated by a zinc-binding FYVE finger. Stenmark, H., Aasland, R., Toh, B.H., D'Arrigo, A. J. Biol. Chem. (1996) [Pubmed]
  22. Molecular cloning and characterization of STAMP2, an androgen-regulated six transmembrane protein that is overexpressed in prostate cancer. Korkmaz, C.G., Korkmaz, K.S., Kurys, P., Elbi, C., Wang, L., Klokk, T.I., Hammarstrom, C., Troen, G., Svindland, A., Hager, G.L., Saatcioglu, F. Oncogene (2005) [Pubmed]
  23. Molecular cloning and characterization of STAMP1, a highly prostate-specific six transmembrane protein that is overexpressed in prostate cancer. Korkmaz, K.S., Elbi, C., Korkmaz, C.G., Loda, M., Hager, G.L., Saatcioglu, F. J. Biol. Chem. (2002) [Pubmed]
  24. CD2AP/CMS regulates endosome morphology and traffic to the degradative pathway through its interaction with Rab4 and c-Cbl. Cormont, M., Metón, I., Mari, M., Monzo, P., Keslair, F., Gaskin, C., McGraw, T.E., Le Marchand-Brustel, Y. Traffic (2003) [Pubmed]
  25. Down-regulation of protease-activated receptor-1 is regulated by sorting nexin 1. Wang, Y., Zhou, Y., Szabo, K., Haft, C.R., Trejo, J. Mol. Biol. Cell (2002) [Pubmed]
  26. Sequential roles for phosphatidylinositol 3-phosphate and Rab5 in tethering and fusion of early endosomes via their interaction with EEA1. Lawe, D.C., Chawla, A., Merithew, E., Dumas, J., Carrington, W., Fogarty, K., Lifshitz, L., Tuft, R., Lambright, D., Corvera, S. J. Biol. Chem. (2002) [Pubmed]
  27. The chloride channel ClC-4 co-localizes with cystic fibrosis transmembrane conductance regulator and may mediate chloride flux across the apical membrane of intestinal epithelia. Mohammad-Panah, R., Ackerley, C., Rommens, J., Choudhury, M., Wang, Y., Bear, C.E. J. Biol. Chem. (2002) [Pubmed]
  28. Immunocytochemical localization of Shc and activated EGF receptor in early endosomes after EGF stimulation of HeLa cells. Oksvold, M.P., Skarpen, E., Lindeman, B., Roos, N., Huitfeldt, H.S. J. Histochem. Cytochem. (2000) [Pubmed]
  29. Sorting nexin 5 is localized to a subdomain of the early endosomes and is recruited to the plasma membrane following EGF stimulation. Merino-Trigo, A., Kerr, M.C., Houghton, F., Lindberg, A., Mitchell, C., Teasdale, R.D., Gleeson, P.A. J. Cell. Sci. (2004) [Pubmed]
  30. A GTPase-activating protein controls Rab5 function in endocytic trafficking. Haas, A.K., Fuchs, E., Kopajtich, R., Barr, F.A. Nat. Cell Biol. (2005) [Pubmed]
  31. Rabenosyn-5, a novel Rab5 effector, is complexed with hVPS45 and recruited to endosomes through a FYVE finger domain. Nielsen, E., Christoforidis, S., Uttenweiler-Joseph, S., Miaczynska, M., Dewitte, F., Wilm, M., Hoflack, B., Zerial, M. J. Cell Biol. (2000) [Pubmed]
  32. Association of early endosomal autoantigen 1 with macropinocytosis in EGF-stimulated A431 cells. Hamasaki, M., Araki, N., Hatae, T. The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology. (2004) [Pubmed]
  33. Endocytic mechanisms responsible for uptake of GPI-linked diphtheria toxin receptor. Skretting, G., Torgersen, M.L., van Deurs, B., Sandvig, K. J. Cell. Sci. (1999) [Pubmed]
  34. Identification of the B-cell epitopes of the early endosome antigen 1 (EEA1). Selak, S., Mahler, M., Miyachi, K., Fritzler, M.L., Fritzler, M.J. Clin. Immunol. (2003) [Pubmed]
  35. Early endosome antigen. 1: An autoantigen associated with neurological diseases. Selak, S., Chan, E.K., Schoenroth, L., Senécal, J.L., Fritzler, M.J. J. Investig. Med. (1999) [Pubmed]
  36. Identification of GRASP-1 as a novel 97 kDa autoantigen localized to endosomes. Stinton, L.M., Selak, S., Fritzler, M.J. Clin. Immunol. (2005) [Pubmed]
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