Gene Symbol: Eea1
Description: early endosome antigen 1
Alias: A430109M19Rik, B230358H09Rik, ZFYVE2, early endosome antigen 1
Species: mouse
Products:     Eea1

Top Publications

  1. Gurung R, Tan A, Ooms L, McGrath M, Huysmans R, Munday A, et al. Identification of a novel domain in two mammalian inositol-polyphosphate 5-phosphatases that mediates membrane ruffle localization. The inositol 5-phosphatase skip localizes to the endoplasmic reticulum and translocates to membrane ruffles following . J Biol Chem. 2003;278:11376-85 pubmed
    ..Collectively, these studies demonstrate a novel membrane-targeting domain that serves to recruit SKIP and PIPP to membrane ruffles. ..
  2. Berger P, Berger I, Schaffitzel C, Tersar K, Volkmer B, Suter U. Multi-level regulation of myotubularin-related protein-2 phosphatase activity by myotubularin-related protein-13/set-binding factor-2. Hum Mol Genet. 2006;15:569-79 pubmed
  3. Liu J, Ding J, Wu C, Bhagavatula P, Cui B, Chu S, et al. Retrolinkin, a membrane protein, plays an important role in retrograde axonal transport. Proc Natl Acad Sci U S A. 2007;104:2223-8 pubmed
    ..Our work lays the foundation for understanding fundamental issues of axonal transport and provides insights into the molecular mechanisms underlying human neurodegenerative disorders. ..
  4. Leem J, Vijayan S, Han P, Cai D, Machura M, Lopes K, et al. Presenilin 1 is required for maturation and cell surface accumulation of nicastrin. J Biol Chem. 2002;277:19236-40 pubmed
    ..Our findings are consistent with PS1 influencing gamma-secretase processing at multiple steps, including maturation and intracellular trafficking of substrates and component(s) of the gamma-secretase complex. ..
  5. Mace G, Miaczynska M, Zerial M, Nebreda A. Phosphorylation of EEA1 by p38 MAP kinase regulates mu opioid receptor endocytosis. EMBO J. 2005;24:3235-46 pubmed
    ..We found that p38alpha can phosphorylate the Rab5 effectors EEA1 and Rabenosyn-5 on Thr-1392 and Ser-215, respectively, and these phosphorylation events regulate the recruitment of ..
  6. Mayer P, Huang N, Dewey C, Dries D, Zhang H, Yu G. Expression, localization, and biochemical characterization of nicotinamide mononucleotide adenylyltransferase 2. J Biol Chem. 2010;285:40387-96 pubmed publisher
    ..These studies show that Nmnat2 is a neuronal protein peripherally attached to membranes via palmitoylation and suggest that Nmnat2 is transported to synaptic terminals via an endosomal pathway. ..
  7. Qin Y, Deng Y, Ricketts C, Srikantan S, Wang E, Maher E, et al. The tumor susceptibility gene TMEM127 is mutated in renal cell carcinomas and modulates endolysosomal function. Hum Mol Genet. 2014;23:2428-39 pubmed publisher
    ..Our data map the tumor-suppressive properties of TMEM127 to modulation of mTOR function in the endolysosome, a feature that may contribute to both pheochromocytoma and RCC pathogenesis. ..
  8. Lighthouse J, Zhang L, Hsieh J, Rosenquist T, Holdener B. MESD is essential for apical localization of megalin/LRP2 in the visceral endoderm. Dev Dyn. 2011;240:577-88 pubmed publisher
    ..Combined, our results provide evidence that MESD functions as a general LRP chaperone and suggest that the Mesd phenotype results from both signaling and endocytic defects resulting from misfolding of multiple LRP receptors...
  9. Lucitti J, Sealock R, Buckley B, Zhang H, Xiao L, Dudley A, et al. Variants of Rab GTPase-Effector Binding Protein-2 Cause Variation in the Collateral Circulation and Severity of Stroke. Stroke. 2016;47:3022-3031 pubmed
    ..Naturally occurring variants of Rabep2 are major determinants of variation in collateral extent and stroke severity in mice. ..

More Information


  1. Craven R, Hall J, Fuller J, Taft Benz S, Kawula T. Francisella tularensis invasion of lung epithelial cells. Infect Immun. 2008;76:2833-42 pubmed publisher
    ..Once internalized, F. tularensis-containing endosomes associated with early endosome antigen 1 (EEA1) followed by lysosome-associated membrane protein 1 (LAMP-1), with peak coassociation frequencies ..
  2. Maurer M, Cooper J. Endocytosis of megalin by visceral endoderm cells requires the Dab2 adaptor protein. J Cell Sci. 2005;118:5345-55 pubmed
    ..These studies suggest that Dab2 p96 mediates endocytosis of megalin in the VE. In addition, rescue of embryonic viability correlates with endocytosis, suggesting that endocytosis mediated by Dab2 is important for normal development. ..
  3. Baker Z, Jett K, Boulet A, Hossain A, Cobine P, Kim B, et al. The mitochondrial metallochaperone SCO1 maintains CTR1 at the plasma membrane to preserve copper homeostasis in the murine heart. Hum Mol Genet. 2017;26:4617-4628 pubmed publisher
  4. Misawa H, Fujigaya H, Nishimura T, Moriwaki Y, Okuda T, Kawashima K, et al. Aberrant trafficking of the high-affinity choline transporter in AP-3-deficient mice. Eur J Neurosci. 2008;27:3109-17 pubmed publisher
    ..The amounts of CHT detected on SLMV are greatly reduced by treating the cell with agents that halt AP-dependent membrane trafficking. These results demonstrate that APs have important functions for CHT trafficking in neuronal cells. ..
  5. Luo L, King N, Yeo J, Jones A, Stow J. Single-step protease cleavage elution for identification of protein-protein interactions from GST pull-down and mass spectrometry. Proteomics. 2014;14:19-23 pubmed publisher
    ..Our protease cleavage step is readily applicable to all further affinity tag pull-downs. ..
  6. Peng C, Ye J, Yan S, Kong S, Shen Y, Li C, et al. Ablation of vacuole protein sorting 18 (Vps18) gene leads to neurodegeneration and impaired neuronal migration by disrupting multiple vesicle transport pathways to lysosomes. J Biol Chem. 2012;287:32861-73 pubmed
    ..Our results demonstrate important roles of Vps18 in neuron survival and migration, which are disrupted in multiple neural disorders. ..
  7. Mishra A, Eathiraj S, Corvera S, Lambright D. Structural basis for Rab GTPase recognition and endosome tethering by the C2H2 zinc finger of Early Endosomal Autoantigen 1 (EEA1). Proc Natl Acad Sci U S A. 2010;107:10866-71 pubmed publisher
    ..of endosomal trafficking by Rab GTPases depends on selective interactions with multivalent effectors, including EEA1 and Rabenosyn-5, which facilitate endosome tethering, sorting, and fusion...
  8. Urresti J, Ruiz Meana M, Coccia E, Arévalo J, Castellano J, Fernández Sanz C, et al. Lifeguard Inhibits Fas Ligand-mediated Endoplasmic Reticulum-Calcium Release Mandatory for Apoptosis in Type II Apoptotic Cells. J Biol Chem. 2016;291:1221-34 pubmed publisher
    ..On the basis of our observations, we propose that there is a required step in the induction of type II apoptotic cell death that involves calcium mobilization from the ER and that this step is modulated by LFG. ..
  9. Hryciw T, MacDonald J, Phillips R, Seah C, Pasternak S, Meakin S. The fibroblast growth factor receptor substrate 3 adapter is a developmentally regulated microtubule-associated protein expressed in migrating and differentiated neurons. J Neurochem. 2010;112:924-39 pubmed publisher
    ..Collectively, these data suggest that neuronal Frs3 functions as a novel microtubule binding protein and they provide the first biochemical evidence that neuronal Frs3 is functionally distinct from Frs2/Frs2alpha. ..
  10. Hatanaka T, Hatanaka Y, Setou M. Regulation of amino acid transporter ATA2 by ubiquitin ligase Nedd4-2. J Biol Chem. 2006;281:35922-30 pubmed
  11. Reed B, Cefalu C, Bellaire B, Cardelli J, Louis T, Salamon J, et al. GLUT1CBP(TIP2/GIPC1) interactions with GLUT1 and myosin VI: evidence supporting an adapter function for GLUT1CBP. Mol Biol Cell. 2005;16:4183-201 pubmed
  12. Seaman M. Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer. J Cell Biol. 2004;165:111-22 pubmed
    ..The data presented here support the hypothesis that retromer performs a selective function in endosome-to-Golgi transport, mediating retrieval of the CI-MPR, but not furin. ..
  13. Cataldo A, Petanceska S, Peterhoff C, Terio N, Epstein C, Villar A, et al. App gene dosage modulates endosomal abnormalities of Alzheimer's disease in a segmental trisomy 16 mouse model of down syndrome. J Neurosci. 2003;23:6788-92 pubmed
    ..These results identify an essential role for App gene triplication in causing AD-related endosomal abnormalities and further establish the pathogenic significance of endosomal dysfunction in AD. ..
  14. Bartuzi P, Billadeau D, Favier R, Rong S, Dekker D, Fedoseienko A, et al. CCC- and WASH-mediated endosomal sorting of LDLR is required for normal clearance of circulating LDL. Nat Commun. 2016;7:10961 pubmed publisher
    ..Altogether, this study provides valuable insights into the mechanisms regulating cholesterol homeostasis and LDLR trafficking. ..
  15. Maric J, Kiss R, Franklin V, Marcel Y. Intracellular lipidation of newly synthesized apolipoprotein A-I in primary murine hepatocytes. J Biol Chem. 2005;280:39942-9 pubmed
    ..Kiss, R. S., Franklin, V., Wang, M. D., Haidar, B., and Marcel, Y. L. (2005) J. Biol. Chem. 280, 21612-21621) occurs after secretion at the cell surface...
  16. Kane L, Watkins S. Dynamic regulation of Tec kinase localization in membrane-proximal vesicles of a T cell clone revealed by total internal reflection fluorescence and confocal microscopy. J Biol Chem. 2005;280:21949-54 pubmed
    ..confocal microscopy, confirming the membrane-proximal location of Tec vesicles, as well as demonstrating overlap of these vesicles with the tyrosine kinase Lck, the Tec substrate PLC-gamma1, and the early endosomal antigen 1 marker EEA1.
  17. Liu L, Fujino K, Nishimura M. Pre-synaptic localization of the γ-secretase-inhibiting protein p24α2 in the mammalian brain. J Neurochem. 2015;133:422-31 pubmed publisher
    ..p24α2 expression is highest in the post-natal period and gradually decreases with age. Our results suggest a novel function for p24α2 at the synapse, including the regulation of brain Aβ generation. ..
  18. Coumailleau F, Das V, Alcover A, Raposo G, Vandormael Pournin S, Le Bras S, et al. Over-expression of Rififylin, a new RING finger and FYVE-like domain-containing protein, inhibits recycling from the endocytic recycling compartment. Mol Biol Cell. 2004;15:4444-56 pubmed
    ..Rffl overexpression represents a novel means to inhibit recycling that will help to understand the mechanisms involved in recycling from the ERC to the plasma membrane. ..
  19. Deane E, Ilie A, Sizdahkhani S, Das Gupta M, Orlowski J, McKinney R. Enhanced recruitment of endosomal Na+/H+ exchanger NHE6 into Dendritic spines of hippocampal pyramidal neurons during NMDA receptor-dependent long-term potentiation. J Neurosci. 2013;33:595-610 pubmed publisher
    ..These data suggest that NHE6 may play a unique, previously unrecognized, role at glutamatergic synapses that are important for learning and memory...
  20. Stober C, Brode S, White J, Popoff J, Blackwell J. Slc11a1, formerly Nramp1, is expressed in dendritic cells and influences major histocompatibility complex class II expression and antigen-presenting cell function. Infect Immun. 2007;75:5059-67 pubmed
    ..These data indicate that wild-type Slc11a1 expressed in DCs may play a role both in determining resistance to infectious disease and in susceptibility to autoimmune disease such as type 1 diabetes. ..
  21. Essalmani R, Susan Resiga D, Chamberland A, Asselin M, Canuel M, Constam D, et al. Furin is the primary in vivo convertase of angiopoietin-like 3 and endothelial lipase in hepatocytes. J Biol Chem. 2013;288:26410-8 pubmed publisher
    ..However, the lack of furin or PC5/6 in hepatocytes and complete PACE4 KO did not appreciably modify plasma HDL levels or EL activity. Thus, inhibition of furin in liver would not be expected to modify the plasma lipid profiles. ..
  22. Krey J, Dumont R, Wilmarth P, David L, Johnson K, Barr Gillespie P. ELMOD1 Stimulates ARF6-GTP Hydrolysis to Stabilize Apical Structures in Developing Vestibular Hair Cells. J Neurosci. 2018;38:843-857 pubmed publisher
  23. Jones C, Hammer R, Li W, Cohen J, Hobbs H, Herz J. Normal sorting but defective endocytosis of the low density lipoprotein receptor in mice with autosomal recessive hypercholesterolemia. J Biol Chem. 2003;278:29024-30 pubmed
    ..Taken together, these results are consistent with ARH playing a critical and specific role in LDLR endocytosis in the liver. ..
  24. Liu L, Watanabe N, Akatsu H, Nishimura M. Neuronal expression of ILEI/FAM3C and its reduction in Alzheimer's disease. Neuroscience. 2016;330:236-46 pubmed publisher
    ..Our results suggest that a decline of ILEI expression may cause accumulation of A? in the brain and the eventual development of AD. ..
  25. REMIS N, Wiwatpanit T, Castiglioni A, Flores E, Cantú J, García Añoveros J. Mucolipin co-deficiency causes accelerated endolysosomal vacuolation of enterocytes and failure-to-thrive from birth to weaning. PLoS Genet. 2014;10:e1004833 pubmed publisher
    ..Finally, we conclude that mucolipin-endowed lysosomes in the young play an evolutionarily-conserved role in the intracellular digestion of maternally-provided nutrients, whether milk in mammals or yolk in oviparous species. ..
  26. Nechiporuk T, Fernandez T, Vasioukhin V. Failure of epithelial tube maintenance causes hydrocephalus and renal cysts in Dlg5-/- mice. Dev Cell. 2007;13:338-50 pubmed
    ..These findings show that Dlg5 is causally involved in hydrocephalus and renal cysts and reveal that targeted membrane delivery of cadherin-catenin adhesion complexes is critical for cell polarity and epithelial tube maintenance. ..
  27. Sun Y, Nishikawa K, Yuda H, Wang Y, Osaka H, Fukazawa N, et al. Solo/Trio8, a membrane-associated short isoform of Trio, modulates endosome dynamics and neurite elongation. Mol Cell Biol. 2006;26:6923-35 pubmed fluorescent protein-Solo/Trio8 localization to early endosomes (positive for both early-endosome antigen 1 [EEA1] and Rab5) in COS-7 cells and primary cultured neurons...
  28. Fossale E, Wolf P, Espinola J, Lubicz Nawrocka T, Teed A, Gao H, et al. Membrane trafficking and mitochondrial abnormalities precede subunit c deposition in a cerebellar cell model of juvenile neuronal ceroid lipofuscinosis. BMC Neurosci. 2004;5:57 pubmed
    ..Moreover, these deficiencies are likely to be early events in the JNCL disease process and may particularly impact neuronal survival. ..
  29. Best D, Adams I. Sdmg1 is a component of secretory granules in mouse secretory exocrine tissues. Dev Dyn. 2009;238:223-31 pubmed publisher
    ..These data suggest that Sdmg1 is a component of regulated secretory granules in exocrine secretory cells and that the developmental regulation of Sdmg1 expression is related to a role for Sdmg1 in post-Golgi membrane trafficking. ..
  30. Liu L, He B, Liu W, Zhou D, Cox J, Zhang X. Tetraspanin CD151 promotes cell migration by regulating integrin trafficking. J Biol Chem. 2007;282:31631-42 pubmed
    ..In conclusion, the YXXvarphi motif-mediated internalization of CD151 promotes integrin-dependent cell migration by modulating the endocytosis and/or vesicular trafficking of its associated integrins. ..
  31. Du G, Huang P, Liang B, Frohman M. Phospholipase D2 localizes to the plasma membrane and regulates angiotensin II receptor endocytosis. Mol Biol Cell. 2004;15:1024-30 pubmed
  32. Prashar A, Bhatia S, Gigliozzi D, Martin T, Duncan C, Guyard C, et al. Filamentous morphology of bacteria delays the timing of phagosome morphogenesis in macrophages. J Cell Biol. 2013;203:1081-97 pubmed publisher
    ..pneumophila to escape phagosomal killing in a length-dependent manner. Our results demonstrate that key aspects in phagocytic cup remodeling and phagosomal maturation could be influenced by target morphology. ..
  33. Liegel R, Handley M, Ronchetti A, Brown S, Langemeyer L, Linford A, et al. Loss-of-function mutations in TBC1D20 cause cataracts and male infertility in blind sterile mice and Warburg micro syndrome in humans. Am J Hum Genet. 2013;93:1001-14 pubmed publisher
  34. Gouttenoire E, Lupo V, Calpena E, Bartesaghi L, Schüpfer F, Medard J, et al. Sh3tc2 deficiency affects neuregulin-1/ErbB signaling. Glia. 2013;61:1041-51 pubmed publisher
    ..Altogether, our results indicate that the molecular mechanism for the axonal size sensing is disturbed in Sh3tc2-deficient myelinating Schwann cells, thus providing a novel insight into the pathophysiology of CMT4C neuropathy. ..
  35. Yu T, Calvo L, Anta B, L pez Benito S, L pez Bellido R, Vicente Garc a C, et al. In vivo regulation of NGF-mediated functions by Nedd4-2 ubiquitination of TrkA. J Neurosci. 2014;34:6098-106 pubmed publisher
    ..Our results indicate that the ubiquitination of the TrkA neurotrophin receptor plays a critical role in NGF-mediated functions, such as neuronal survival and sensitivity to pain...
  36. Huber C, Martensson A, Bokoch G, Nemazee D, Gavin A. FGD2, a CDC42-specific exchange factor expressed by antigen-presenting cells, localizes to early endosomes and active membrane ruffles. J Biol Chem. 2008;283:34002-12 pubmed publisher
    ..These findings are consistent with a role of FGD2 in leukocyte signaling and vesicle trafficking in cells specialized to present antigen in the immune system. ..
  37. Mestres I, Chuang J, Calegari F, Conde C, Sung C. SARA regulates neuronal migration during neocortical development through L1 trafficking. Development. 2016;143:3143-53 pubmed publisher
    ..These results suggest that SARA regulates the orientation, multipolar-to-bipolar transition and the positioning of cortical neurons via modulating surface L1 expression. ..
  38. Kaneko Goto T, Sato Y, Katada S, Kinameri E, Yoshihara S, Nishiyori A, et al. Goofy coordinates the acuity of olfactory signaling. J Neurosci. 2013;33:12987-96, 12996a pubmed publisher
    ..These results demonstrate that Goofy plays an important role in establishing the acuity of olfactory sensory signaling. ..
  39. Fusco C, Micale L, Egorov M, Monti M, D Addetta E, Augello B, et al. The E3-ubiquitin ligase TRIM50 interacts with HDAC6 and p62, and promotes the sequestration and clearance of ubiquitinated proteins into the aggresome. PLoS ONE. 2012;7:e40440 pubmed publisher
    ..We speculate that when the proteasome activity is impaired, TRIM50 fails to drive its substrates to the proteasome-mediated degradation, and promotes their storage in the aggresome for successive clearance...
  40. Voltan A, Sardi J, Soares C, Pelajo Machado M, Fusco Almeida A, Mendes Giannini M. Early Endosome Antigen 1 (EEA1) decreases in macrophages infected with Paracoccidioides brasiliensis. Med Mycol. 2013;51:759-64 pubmed publisher
    ..The aim of this study was to evaluate the expression of the endocytic protein EEA1 (early endosome antigen 1) in macrophages infected with P. brasiliensis...
  41. Tang F, Erion J, Tian Y, Liu W, Yin D, Ye J, et al. VPS35 in Dopamine Neurons Is Required for Endosome-to-Golgi Retrieval of Lamp2a, a Receptor of Chaperone-Mediated Autophagy That Is Critical for α-Synuclein Degradation and Prevention of Pathogenesis of Parkinson's Disease. J Neurosci. 2015;35:10613-28 pubmed publisher
    ..These results suggest that VPS35 deficiency or mutation promotes PD pathogenesis, and reveals a crucial pathway, VPS35-Lamp2a-α-synuclein, to prevent PD pathogenesis. ..
  42. Moldrich R, Laine J, Visel A, Beart P, Laffaire J, Rossier J, et al. Transmembrane protein 50b (C21orf4), a candidate for Down syndrome neurophenotypes, encodes an intracellular membrane protein expressed in the rodent brain. Neuroscience. 2008;154:1255-66 pubmed publisher
    ..Results indicate that Tmem50b is a developmentally-regulated intracellular ER and Golgi apparatus membrane protein that may prove important for correct brain development through functions associated with precursor cells and glia. ..
  43. Selak S, Braun J, Fritzler M. Characterization of early endosome antigen 1 in neural tissues. Biochem Biophys Res Commun. 2004;323:1334-42 pubmed
    The finding that patients and mice bearing autoantibodies directed against early endosome antigen 1 (EEA1) develop neurological signs and deficits prompted an investigation of EEA1 distribution, localization, and interaction with synaptic ..