Affinage

EEA1

Early endosome antigen 1 · UniProt Q15075

Length
1411 aa
Mass
162.5 kDa
Annotated
2026-06-09
43 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EEA1 is a 180-kDa, predominantly alpha-helical peripheral membrane protein that serves as a Rab5 effector and tethering factor governing early endosome fusion (PMID:7768953, PMID:9697774). It assembles into a parallel coiled-coil homodimer (~350 kDa) and is recruited to early endosomes through coincidence detection: its C-terminal FYVE zinc finger binds the PI(3)K product PI(3)P with ~50 nM affinity in a Zn2+-dependent manner—inserting amphipathic loops into the bilayer beyond electrostatic contacts—while a region adjacent to the FYVE domain and an N-terminal C2H2 zinc finger engage GTP-loaded Rab5 (PMID:8798641, PMID:10024533, PMID:10807926, PMID:20534488, PMID:22915584). A crystal structure of the Rab5A–C2H2 finger complex shows this interface is restricted to the Rab5 switch/interswitch regions and confers high selectivity for Rab5 and, more weakly, Rab22 (PMID:20534488). PI(3)P binding mediates the tethering step, after which Rab5 interaction promotes the subsequent membrane fusion step, establishing a sequential tether-then-fuse mechanism required for both homotypic endosome fusion and heterotypic clathrin-coated-vesicle-to-endosome fusion (PMID:9705936, PMID:10660521, PMID:11602609). EEA1 forms a stable complex with syntaxin 6 and binds calmodulin via an IQ motif adjacent to the FYVE domain, with both calmodulin and Rab5-GTP antagonizing FYVE–PI(3)P binding to couple tethering to the fusion machinery (PMID:11329382). Its membrane residence and oligomeric state are regulated post-translationally: p38 MAPK directly phosphorylates Thr-1392 to control recruitment during receptor endocytosis (PMID:16138080), the AAA-ATPase p97 binds the C2H2 finger to limit EEA1 self-association and endosome size (PMID:21556036), and E3-independent monoubiquitination promotes fusion at the expense of recycling (PMID:23701900). Beyond core trafficking, EEA1-positive endosomes act as signaling platforms for TGF-β/Smad2 activation and for angiotensin II–driven Akt/mTOR signaling (PMID:12356868, PMID:21097843).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1995 High

    Established that EEA1 is an early-endosome-specific peripheral membrane protein, distinguishing the early from late endocytic compartment and defining its domain architecture as a starting point for mechanism.

    Evidence Molecular cloning, immunoelectron microscopy, subcellular fractionation and salt extraction in human cells

    PMID:7768953

    Open questions at the time
    • Function in membrane traffic not yet demonstrated
    • Basis of endosome-selective targeting unknown
  2. 1996 High

    Identified the C-terminal cysteine-rich motif as a genuine zinc-binding FYVE finger and showed it is required for endosomal localization, pinpointing the membrane-targeting module.

    Evidence Zinc-binding assays and FYVE-residue mutagenesis with confocal localization in transfected cells

    PMID:8798641

    Open questions at the time
    • Lipid or protein ligand of the FYVE finger not identified
    • Quantitative binding affinity unknown
  3. 1998 High

    Defined EEA1 as a Rab5 effector that binds PI(3)P and is functionally required for early endosome fusion, integrating a GTPase and a lipid into a single fusion-promoting factor.

    Evidence PI(3)P-binding and in vitro endosome fusion assays with dominant-negative PI3K, antibody inhibition and depletion

    PMID:9697774 PMID:9705936

    Open questions at the time
    • Relative order of Rab5 versus PI(3)P engagement unresolved
    • Whether EEA1 tethers or directly catalyzes fusion not separated
  4. 1999 High

    Showed EEA1 is a parallel coiled-coil homodimer and that C-terminal dimerization correlates with Rab5 binding, providing the quaternary structure underlying long-range tethering.

    Evidence Crosslinking, glycerol gradient sedimentation and yeast two-hybrid plus pull-down with Rab5a/b

    PMID:10024533 PMID:10491193

    Open questions at the time
    • Geometry of dimer-mediated tethering across membranes not visualized
    • Contribution of N- versus C-terminal Rab5 sites in cells unclear
  5. 2000 High

    Quantified FYVE–PI(3)P binding (~50 nM, Zn2+-dependent) and demonstrated that PI(3)P recognition is essential for endosomal targeting, and that EEA1 directionality drives heterotypic CCV-to-endosome fusion.

    Evidence Surface plasmon resonance and mutagenesis with localization assays; in vitro heterotypic fusion assay and ultrastructural analysis

    PMID:10660521 PMID:10807926 PMID:10930461

    Open questions at the time
    • How FYVE and Rab5 binding are coordinated temporally not defined
    • Membrane-insertion mode of FYVE not yet resolved
  6. 2001 High

    Separated tethering from fusion mechanistically—PI(3)P binding mediates tethering while Rab5 binding governs subsequent fusion—and identified syntaxin 6 and calmodulin as partners coupling tethering to the fusion machinery.

    Evidence Mutagenesis with Rab5Q79L epistasis and endosome enlargement readouts; GST pull-downs of syntaxins and calmodulin with PI(3)P competition assays

    PMID:11329382 PMID:11602609

    Open questions at the time
    • Molecular trigger that converts a tether into a fusion complex unknown
    • Role of calmodulin antagonism of PI(3)P binding in vivo unclear
  7. 2002 Medium

    Extended Rab effector specificity to Rab22a and implicated EEA1 endosomes as platforms for TGF-β/Smad2 signaling, linking endocytic tethering to receptor signal output.

    Evidence Yeast two-hybrid/pull-down for Rab22a; co-localization and signaling/internalization perturbation for TGF-β receptors and SARA

    PMID:11870209 PMID:12356868

    Open questions at the time
    • Direct requirement of EEA1 for Smad2 activation not tested by loss of function
    • Functional distinction between Rab5- and Rab22-driven recruitment unclear
  8. 2005 High

    Identified EEA1 Thr-1392 as a direct p38 MAPK phosphorylation site controlling membrane recruitment, establishing a kinase input that regulates receptor endocytosis through EEA1.

    Evidence In vitro kinase assay, phosphomimetic rescue in p38α-null cells, MOR endocytosis and membrane recruitment assays; phagosomal regulation by p38

    PMID:12963735 PMID:16138080

    Open questions at the time
    • How Thr-1392 phosphorylation alters PI(3)P/Rab5 binding mechanically unknown
    • Other regulatory phosphosites not mapped
  9. 2008 Medium

    Resolved EEA1 membrane binding into dynamic kinetic fractions and showed mitotic fusion arrest arises from accelerated dissociation, explaining cell-cycle control of endosome fusion.

    Evidence FRAP and photoactivatable-GFP kinetics of EEA1-GFP across the cell cycle; TIRF imaging of EGF/Tf vesicle engagement with EEA1 endosomes

    PMID:18188183 PMID:18827013

    Open questions at the time
    • Mitotic factor that destabilizes EEA1 binding not identified
    • Link between exchange kinetics and cargo sorting decisions unresolved
  10. 2010 High

    Provided the atomic basis for Rab5 recognition by the C2H2 zinc finger and defined EEA1 endosomes as scaffolds for angiotensin II–Akt signaling, broadening EEA1 from tether to signaling hub.

    Evidence X-ray structure of Rab5A–C2H2 complex with selectivity profiling; co-IP, siRNA and signaling readouts in vascular smooth muscle cells

    PMID:20534488 PMID:21097843

    Open questions at the time
    • Whether Akt scaffolding is direct or via adaptors not resolved
    • Structural basis of Rab22/Rab21 cross-reactivity not defined
  11. 2012 Medium

    Established post-translational and partner-based control of EEA1 oligomeric state and signaling: p97 governs self-association and endosome size, while Gαs/GIV tune EGFR signaling from EEA1 endosomes.

    Evidence Co-IP/domain mapping with p97 plus knockdown morphology; siRNA of Gαs/GIV with EGFR signaling, degradation and proliferation assays; NMR of FYVE on PI(3)P-nanodiscs

    PMID:21556036 PMID:22915584 PMID:23051738

    Open questions at the time
    • Mechanism by which p97 ATPase activity remodels EEA1 oligomers unknown
    • Whether Gαs/GIV act on EEA1 directly or on endosome maturation broadly unclear
  12. 2013 Medium

    Showed EEA1 is monoubiquitinated at multiple sites by an E3-independent, E2-affinity-driven mechanism that biases endosomes toward fusion over recycling.

    Evidence Detection of endogenous ubiquitination and ubiquitin-EEA1 chimera expression with endosome morphology and fusion/fission assays

    PMID:23701900

    Open questions at the time
    • Physiological stimulus controlling ubiquitination not identified
    • Specific lysine sites and deubiquitinase not mapped
  13. 2021 Low

    Computationally modeled how the FYVE homodimer engages PI(3)P membranes via a hinge mechanism and how the long coiled-coil enables Rab5 capture over a large search radius.

    Evidence Multi-scale coarse-grained and atomistic molecular dynamics simulations with binding-energy calculations

    PMID:34555023

    Open questions at the time
    • No experimental validation of the proposed hinge mechanism in this study
    • Predicted binding energies not measured directly
  14. 2025 Medium

    Identified Rab21 as a direct EEA1 partner that recruits EEA1 to endosomes in parallel to Rab5, revealing redundancy in effector recruitment through a shared GEF.

    Evidence Co-IP/pull-down, overexpression rescue of PI3P/Rab5 defects, and Rabex-5 competition analysis

    PMID:40519268

    Open questions at the time
    • Structural basis of Rab21–EEA1 binding not defined
    • Physiological context where Rab21 dominates over Rab5 unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple inputs—PI(3)P, competing Rab GTPases, calmodulin, phosphorylation, ubiquitination and p97-controlled oligomerization—are integrated to switch a single EEA1 tether between fusion, recycling and signaling outcomes remains unresolved.
  • No unified model linking PTM state to fusion-versus-recycling decisions
  • Mechanism converting tethered membranes into fusion-competent complexes unknown
  • In vivo hierarchy among Rab5, Rab21 and Rab22 recruitment undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 3 GO:0060090 molecular adaptor activity 3 GO:0005198 structural molecule activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005768 endosome 4 GO:0005829 cytosol 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-162582 Signal Transduction 3
Partners
AKT1CALM1RAB21RAB22ARAB5ARAB5BSTX6VCP

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 EEA1 is a 180-kDa peripheral membrane protein localized to early endosomes (co-localizing with transferrin receptor and Rab5 but not Rab7), present in both cytosol and membrane fractions, extractable by 0.3 M NaCl, predominantly alpha-helical with a calmodulin-binding IQ motif, and flanked by cysteine 'finger' motifs at its C-terminus homologous to yeast proteins involved in vacuolar transport. Molecular cloning, immunofluorescence co-localization, immunoelectron microscopy, subcellular fractionation, Triton X-114 partitioning, salt extraction, sequence analysis The Journal of biological chemistry High 7768953
1996 The C-terminal cysteine-rich motif of EEA1 constitutes a genuine zinc-binding domain (FYVE finger) that binds 2 mol equivalents of Zn2+; mutation of conserved histidine/cysteine residues reduces zinc binding. The FYVE finger is required for endosomal localization: deletion of the FYVE finger or mutations that impair zinc binding cause cytosolic redistribution of EEA1. Zinc-binding assay, site-directed mutagenesis of FYVE finger residues, confocal immunofluorescence of transfected HEp2 cells, profile-based database searches The Journal of biological chemistry High 8798641
1998 EEA1 is a Rab5 effector that binds the PI(3)K product phosphatidylinositol-3-phosphate (PI3P) and is required for early endosome fusion. Association of EEA1 with endosomal membranes requires both Rab5-GTP and PI(3)K activity; excess Rab5-GTP can stabilize membrane-bound EEA1 even when PI(3)K is inhibited. PI3P-binding assay, in vitro endosome fusion assay, dominant-negative PI(3)K inhibition, overexpression of constitutively active Rab5, biochemical membrane association assay Nature High 9697774
1998 EEA1 is functionally required for homotypic fusion of early endosomes in vitro: the C-terminal domain of EEA1 (residues 1098–1411) inhibits endosome fusion when added to the assay, specific anti-EEA1 antibodies inhibit fusion, and depletion of EEA1 from membrane and cytosolic fractions reduces fusion efficiency. In vitro endosome fusion assay, antibody inhibition, salt-wash depletion of EEA1 from membranes, cytosol immunodepletion Current biology : CB High 9705936
1999 EEA1 forms a parallel coiled-coil homodimer (~350 kDa). The N- and C-terminal fragments self-interact but not with each other. C-terminal dimerization correlates with Rab5 binding and endosomal localization, whereas PtdIns3P binding by the C-terminus is independent of dimerization. Chemical crosslinking, glycerol gradient centrifugation, yeast two-hybrid analysis with N- and C-terminal fragments The Biochemical journal High 10024533
1999 EEA1 directly interacts with Rab5b (and Rab5a) via both its N-terminal and C-terminal domains in a GTP-dependent manner, as established by yeast two-hybrid screening of a human brain library and confirmed biochemically by pull-down assay. EEA1 co-localizes with Rab5b on early endosomes. Yeast two-hybrid screen of human brain library, biochemical pull-down assay, confocal immunofluorescence co-localization, GTPase activity assay European journal of biochemistry High 10491193
2000 The FYVE finger of EEA1 binds PI(3)P with an apparent Kd of ~50 nM in a Zn2+-dependent manner (1:1 stoichiometry); mutation of coordinating cysteines, basic residues in the binding pocket (e.g., R1375A), or other conserved residues reduces affinity 6- to >100-fold and causes cytosolic mis-localization of EEA1, demonstrating that PI(3)P binding is essential for endosomal targeting and function. Surface plasmon resonance, site-directed mutagenesis, fluorescence spectroscopy (3D structure verification), confocal immunofluorescence of transfected mammalian cells, early endosome morphology assay The Journal of biological chemistry High 10807926
2000 EEA1 is selectively recruited to early endosome membranes but not to clathrin-coated vesicles (CCVs), and this asymmetric distribution provides directionality for heterotypic fusion of CCVs with early endosomes. EEA1 is required for heterotypic CCV-to-endosome fusion in addition to homotypic endosome fusion, as shown in an in vitro heterotypic fusion assay. In vitro heterotypic fusion assay, immunofluorescence localization of Rab5/Rabaptin-5/EEA1 on CCVs vs. early endosomes, fractionation The Journal of biological chemistry High 10660521
2000 EEA1 is present on a subdomain of the early sorting endosome (but not on clathrin-coated vesicles) and is associated with filamentous material extending from the cytoplasmic endosomal surface, consistent with a tethering/docking role. In polarized cells (MDCK and hippocampal neurons), EEA1 marks only a subset of 'basolateral-type' endosomes, revealing at least two distinct early endosomal populations. Immunoelectron microscopy (ultrastructural analysis), confocal immunofluorescence in MDCK cells and hippocampal neurons, comparison with endotubin (apical endosomal marker) Molecular biology of the cell Medium 10930461
2001 Endosome tethering depends on EEA1 interaction with PI(3)P (via FYVE domain), while EEA1 interaction with Rab5 (via a binding region adjacent to the FYVE domain) regulates subsequent fusion. Point mutations impairing Rab5 but not PI(3)P binding still allow endosome tethering but prevent Rab5Q79L-stimulated endosome enlargement, showing sequential roles for PI(3)P (tethering) then Rab5 (fusion). Site-directed mutagenesis of full-length and truncated EEA1, overexpression in mammalian cells, endosome morphology analysis (live/fixed imaging), co-expression with constitutively active Rab5Q79L The Journal of biological chemistry High 11602609
2001 EEA1 forms a stable complex with syntaxin 6 (but not syntaxin 13) in direct binding assays. EEA1 and syntaxin 13 each interact with calmodulin; EEA1's calmodulin binding requires its IQ domain, which is adjacent to the C-terminal FYVE domain. Calmodulin and Rab5-GTP both antagonize EEA1 binding to PI3P, while syntaxins 6 and 13 do not affect PI3P binding. GST pull-down of EEA1 with immobilized syntaxins 6 and 13, in vitro endosome fusion assay with specific inhibitors (calmodulin antagonists), calmodulin-binding assay, PI3P-binding competition assay Journal of cell science High 11329382
2002 TGF-β type I and II receptors internalize into EEA1-positive early endosomes, and the extent of TGF-β-stimulated Smad2 phosphorylation and nuclear translocation correlates with receptor internalization into these endosomes. SARA (Smad anchor for receptor activation), which contains a FYVE finger, co-localizes with EEA1-positive endosomes; disruption of SARA endosomal localization inhibits TGF-β-induced Smad2 nuclear translocation. Immunofluorescence co-localization, endocytosis inhibition experiments, TGF-β signaling readouts (Smad2 phosphorylation, nuclear translocation, transcription assay), SARA localization disruption The Journal of cell biology Medium 12356868
2002 The GTP-bound form of Rab22a interacts with the N-terminus of EEA1, as shown by yeast two-hybrid and biochemical pull-down. Overexpression of wild-type Rab22a causes formation of large EEA1-positive vacuoles, and the GTPase-deficient Rab22a Q64L mutant interferes with EGF degradation and causes redistribution of transferrin-positive endosomes. Yeast two-hybrid assay, biochemical pull-down, overexpression of wild-type and mutant Rab22a, immunofluorescence co-localization with EEA1/Rab11/LAMP-1, EGF degradation assay Journal of cell science Medium 11870209
2003 p38 MAPK activation negatively regulates EEA1 recruitment to phagosomal membranes: pharmacological inhibition of p38 MAPK increases EEA1 co-localization with mycobacterial phagosomes and promotes phagosomal acidification and acquisition of late endocytic markers, whereas artificial activation of p38 MAPK decreases EEA1 association with model latex bead phagosomes. Pharmacological p38 MAPK inhibition (SB203580) and activation, immunofluorescence co-localization of EEA1 with phagosomes, phagosomal acidification assay, late endocytic marker acquisition The Journal of biological chemistry Medium 12963735
2005 p38α MAPK directly phosphorylates EEA1 on Thr-1392, and this phosphorylation regulates EEA1 membrane recruitment. A phosphomimetic mutation (T1392E/D) of EEA1 bypasses the requirement for p38α in mu opioid receptor (MOR) endocytosis, establishing EEA1 as a functional downstream target of p38 MAPK in receptor internalization. In vitro kinase assay (p38α phosphorylation of EEA1), site-directed mutagenesis (phosphomimetic T1392), p38α-/- cells, MOR endocytosis assay, membrane recruitment assay The EMBO journal High 16138080
2008 EEA1-GFP cycles on and off early endosomal membranes throughout the cell cycle with two kinetic fractions: a rapidly exchanging fraction and a long-lived membrane-bound fraction. During mitosis, the dissociation rate is markedly accelerated and the long-lived fraction is greatly reduced, indicating that endosome fusion arrest in mitosis results from altered EEA1 membrane-binding kinetics rather than complete loss of binding. FRAP (fluorescence recovery after photobleaching) of EEA1-GFP, photoactivatable GFP to separate release vs. binding rates, cell-cycle stage determination EMBO reports Medium 18188183
2008 EGF and transferrin (Tf) are incorporated into distinct endocytic vesicles from separate plasma membrane regions; both types interact with EEA1-positive endosomes, but EGF-enriched vesicles recruit more Rab5 GTPase than Tf-enriched vesicles, strengthening their association with EEA1 endosomes and directing EGF to degradation while Tf rapidly dissociates to recycling compartments. Total internal reflection fluorescence microscopy (TIRF-M) of live cells, fluorescently labeled EGF and transferrin, EEA1 and Rab5 co-imaging Journal of cell science Medium 18827013
2010 Crystal structure of Rab5A in complex with the EEA1 N-terminal C2H2 zinc finger reveals that the binding interface involves all elements of the zinc finger plus a short N-terminal extension and is restricted to the switch and interswitch regions of Rab5. EEA1 C2H2 zinc finger shows high selectivity for Rab5 and, to a lesser extent, Rab22. Rab4-to-Rab5 specificity conversion requires substitutions both in switch regions and in the proximal protein core. X-ray crystal structure of Rab5A–EEA1 C2H2 zinc finger complex, quantitative binding profiles across Rab GTPase family, Rab4-to-Rab5 specificity conversion mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 20534488
2010 EEA1-positive early endosomes are a major site of angiotensin II-induced Akt activation in vascular smooth muscle cells. EEA1 serves as a scaffold: both Akt and phospho-Akt interact with EEA1 (co-IP), EEA1 expression is required for Akt phosphorylation at Thr-308 and Ser-473 and for downstream mTOR and S6K phosphorylation, and PKC-α is required upstream of EEA1-dependent Akt signaling. Cell fractionation, co-immunoprecipitation of EEA1 with Akt/p-Akt, EEA1 siRNA knockdown, fluorescence imaging, PKC-α dominant-negative expression, leucine incorporation assay The Journal of biological chemistry Medium 21097843
2011 The AAA-ATPase p97 associates with EEA1 via its N-terminal C2H2 zinc finger domain; a fraction of p97 localizes to early endosome membranes. Inhibition of p97 (by siRNA or pharmacological inhibitor) causes clustering and enlargement of early endosomes and altered endocytic cargo trafficking, associated with increased EEA1 self-association at the endosome membrane. p97 is proposed to regulate early endosome size by governing EEA1 oligomeric state. Co-immunoprecipitation, domain-mapping pull-down (N-terminal C2H2 zinc finger), p97 siRNA knockdown, pharmacological p97 inhibition, early endosome fractionation, endosome morphology analysis, EEA1 self-association assay Cell research Medium 21556036
2012 Gαs promotes EEA1-endosome maturation and dampens EGFR proliferative signaling through interaction with GIV/Girdin. When Gαs or GIV is depleted, activated EGFR accumulates in EEA1 endosomes, signaling is prolonged, EGFR downregulation is delayed, and cell proliferation increases, establishing EEA1 endosomes as major sites of proliferative EGFR signaling regulated by this pathway. siRNA depletion of Gαs and GIV, EGFR/EEA1 co-localization imaging, EGFR signaling assays (phospho-EGFR, downstream signaling), EGFR degradation assay, cell proliferation assay Molecular biology of the cell Medium 23051738
2013 Endogenous EEA1 undergoes monoubiquitination at multiple sites via an E3-independent mechanism driven by intrinsic affinity for ubiquitin-conjugating enzymes (E2). Expression of a ubiquitin-EEA1 chimera mimicking mono-ubiquitinated EEA1 causes giant endosome formation near the nucleus due to increased endosome fusion and a concomitant block in an endosome recycling/fission pathway. Detection of endogenous EEA1 ubiquitination, ubiquitin-EEA1 chimera expression, endosome morphology analysis, endosome fusion/fission assays Cell & bioscience Medium 23701900
2012 NMR analyses using PI(3)P-nanodiscs identified the residue-specific interaction surface, structural change, and relative orientation of the EEA1 FYVE domain when bound to PI(3)P in a lipid bilayer environment, showing that FYVE inserts amphipathic loops into the bilayer in addition to electrostatic PI(3)P interactions. NMR chemical shift perturbation, transferred cross-saturation, paramagnetic relaxation enhancement experiments using PI(3)P-containing nanodiscs The Journal of biological chemistry Medium 22915584
2021 Multi-scale MD simulations reveal that the EEA1 FYVE homodimer binds PI(3)P-containing membranes via a hinge mechanism (C-terminus of one monomer attaches first, then the other), with ~70 kJ/mol total binding energy (~50-60 kJ/mol from specific PI(3)P interactions); FYVE also inserts amphipathic loops. The 200 nm coiled-coil allows the Rab5-binding N-terminal domain to explore ~0.1 μm2 for endosome tethering. Coarse-grained and atomistic molecular dynamics simulations, binding energy calculations, comparison with crystal structure (PDB 1JOC) PLoS computational biology Low 34555023
2025 Rab21 (a Rab5 subfamily member) directly interacts with EEA1 and recruits it to early endosomes via a pathway parallel to Rab5. Overexpression of Rab21 rescues EEA1 mis-localization and endosomal size defects caused by PI3P depletion or Rab5 function inhibition. Rab5 and Rab21 compete for activation by their shared GEF Rabex-5. Co-immunoprecipitation/pull-down (Rab21-EEA1 interaction), overexpression rescue experiments (EEA1 localization, endosomal size), dominant-negative Rab5/Rab21 mutants and Rabex-5 binding analysis Frontiers in cell and developmental biology Medium 40519268

Source papers

Stage 0 corpus · 43 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 EEA1 links PI(3)K function to Rab5 regulation of endosome fusion. Nature 939 9697774
1995 EEA1, an early endosome-associated protein. EEA1 is a conserved alpha-helical peripheral membrane protein flanked by cysteine "fingers" and contains a calmodulin-binding IQ motif. The Journal of biological chemistry 623 7768953
1996 Endosomal localization of the autoantigen EEA1 is mediated by a zinc-binding FYVE finger. The Journal of biological chemistry 403 8798641
2002 TGF beta receptor internalization into EEA1-enriched early endosomes: role in signaling to Smad2. The Journal of cell biology 249 12356868
1998 Involvement of the endosomal autoantigen EEA1 in homotypic fusion of early endosomes. Current biology : CB 197 9705936
2000 EEA1, a tethering protein of the early sorting endosome, shows a polarized distribution in hippocampal neurons, epithelial cells, and fibroblasts. Molecular biology of the cell 163 10930461
2000 Selective membrane recruitment of EEA1 suggests a role in directional transport of clathrin-coated vesicles to early endosomes. The Journal of biological chemistry 138 10660521
2002 The small GTPase Rab22 interacts with EEA1 and controls endosomal membrane trafficking. Journal of cell science 131 11870209
2000 Interaction of the EEA1 FYVE finger with phosphatidylinositol 3-phosphate and early endosomes. Role of conserved residues. The Journal of biological chemistry 124 10807926
2005 Phosphorylation of EEA1 by p38 MAP kinase regulates mu opioid receptor endocytosis. The EMBO journal 123 16138080
2001 Sequential roles for phosphatidylinositol 3-phosphate and Rab5 in tethering and fusion of early endosomes via their interaction with EEA1. The Journal of biological chemistry 111 11602609
2008 Sorting of EGF and transferrin at the plasma membrane and by cargo-specific signaling to EEA1-enriched endosomes. Journal of cell science 99 18827013
1999 The endosome fusion regulator early-endosomal autoantigen 1 (EEA1) is a dimer. The Biochemical journal 95 10024533
2011 The p97 ATPase associates with EEA1 to regulate the size of early endosomes. Cell research 90 21556036
2003 Induction of p38 mitogen-activated protein kinase reduces early endosome autoantigen 1 (EEA1) recruitment to phagosomal membranes. The Journal of biological chemistry 90 12963735
2001 Relationships between EEA1 binding partners and their role in endosome fusion. Journal of cell science 85 11329382
2010 Structural basis for Rab GTPase recognition and endosome tethering by the C2H2 zinc finger of Early Endosomal Autoantigen 1 (EEA1). Proceedings of the National Academy of Sciences of the United States of America 84 20534488
2015 Internalization of the TGF-β type I receptor into caveolin-1 and EEA1 double-positive early endosomes. Cell research 72 25998683
1999 Direct interaction of EEA1 with Rab5b. European journal of biochemistry 52 10491193
2010 Early endosomal antigen 1 (EEA1) is an obligate scaffold for angiotensin II-induced, PKC-alpha-dependent Akt activation in endosomes. The Journal of biological chemistry 46 21097843
2012 Gαs promotes EEA1 endosome maturation and shuts down proliferative signaling through interaction with GIV (Girdin). Molecular biology of the cell 43 23051738
2018 Endosomal Escape of Antisense Oligonucleotides Internalized by Stabilin Receptors Is Regulated by Rab5C and EEA1 During Endosomal Maturation. Nucleic acid therapeutics 39 29437530
2020 Functional cycle of EEA1-positive early endosome: Direct evidence for pre-existing compartment of degradative pathway. PloS one 28 32357161
2017 EEA1 restores homeostatic synaptic plasticity in hippocampal neurons from Rett syndrome mice. The Journal of physiology 26 28621434
2008 Cell-cycle-dependent binding kinetics for the early endosomal tethering factor EEA1. EMBO reports 25 18188183
2015 ESCRT-0 marks an APPL1-independent transit route for EGFR between the cell surface and the EEA1-positive early endosome. Journal of cell science 22 25588841
2012 NMR analyses of the interaction between the FYVE domain of early endosome antigen 1 (EEA1) and phosphoinositide embedded in a lipid bilayer. The Journal of biological chemistry 22 22915584
2011 Knockdown of STEAP4 inhibits insulin-stimulated glucose transport and GLUT4 translocation via attenuated phosphorylation of Akt, independent of the effects of EEA1. Molecular medicine reports 22 21468601
2013 Monoubiquitination of EEA1 regulates endosome fusion and trafficking. Cell & bioscience 21 23701900
2015 IQGAP1 promotes CXCR4 chemokine receptor function and trafficking via EEA-1+ endosomes. The Journal of cell biology 20 26195666
2003 Identification of the B-cell epitopes of the early endosome antigen 1 (EEA1). Clinical immunology (Orlando, Fla.) 17 14597214
2017 High Resolution Localization of Rab5, EEA1, and Nectin-3 to Tubulobulbar Complexes in the Rat Testis. Anatomical record (Hoboken, N.J. : 2007) 13 28176461
2000 Autoantibodies to early endosome antigen (EEA1) produce a staining pattern resembling cytoplasmic anti-neutrophil cytoplasmic antibodies (C-ANCA). Clinical and experimental immunology 13 11122260
2021 Membrane-binding mechanism of the EEA1 FYVE domain revealed by multi-scale molecular dynamics simulations. PLoS computational biology 11 34555023
2020 Quantitative Immunoblotting Analyses Reveal that the Abundance of Actin, Tubulin, Synaptophysin and EEA1 Proteins is Altered in the Brains of Aged Mice. Neuroscience 11 32652177
2013 Early Endosome Antigen 1 (EEA1) decreases in macrophages infected with Paracoccidioides brasiliensis. Medical mycology 9 23566224
2014 [Analysis of vesicle subpopulations carrying early endosomal autoantigen EEA1]. Tsitologiia 3 25711083
2025 Motor Function of the Two-Component EEA1-Rab5 Revealed by dcFCCS. Methods in molecular biology (Clifton, N.J.) 2 39704939
2016 EEA1 CARRYING VESICLES ARE NOT AUTOPHAGOSOMES IN SERUM-DEPRIVED HeLa CELLS. Tsitologiia 2 30188634
2025 Rab21 recruits EEA1 and competes with Rab5 for Rabex-5 activation. Frontiers in cell and developmental biology 1 40519268
2016 Mobility of tethering factor EEA1 on endosomes is decreased upon stimulation of EGF receptor endocytosis in HeLa cells. Biochemical and biophysical research communications 1 26993163
2026 A QCM-D Study of the Interaction of Early Endosomal Antigen 1 (EEA1) Protein with Supported Lipid Bilayers Mimicking the Early Endosomal Lipid Composition. Membranes 0 41745491
2025 Host factor Rab4b mediates internalization and intoxication of 3D4/21 cells by the active subunit of the Glaesserella parasuis cytolethal distending toxin via influencing EEA1 expression. Frontiers in microbiology 0 41244687

Missed literature

Know a paper Affinage missed for EEA1? Flag it for the maintainers and the community.

No submissions yet.