Affinage

EPS15

Epidermal growth factor receptor substrate 15 · UniProt P42566

Length
896 aa
Mass
98.7 kDa
Annotated
2026-06-09
100 papers in source corpus 50 papers cited in narrative 50 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EPS15 is a multidomain endocytic adaptor that nucleates and organizes clathrin-coated pit assembly at the plasma membrane and couples ubiquitinated receptor cargo to clathrin-mediated internalization (PMID:8557749, PMID:8910509, PMID:10194409). It is constitutively associated with the AP-2 clathrin adaptor through C-terminal determinants that engage the alpha-adaptin ear domain, and it localizes specifically to the rim of forming coated pits rather than distributing uniformly with AP-2 (PMID:8557749, PMID:8910509, PMID:9000562). Disrupting either the AP-2-binding C-terminus or the EH domains acts as a dominant negative that abolishes AP-2/clathrin punctate organization and blocks transferrin and EGF endocytosis, establishing that EPS15 is required for coated-pit assembly and AP-2 docking; efficient pit targeting requires cooperation between its EH domains and its AP-2 sites (PMID:9490719, PMID:10194409, PMID:10652316). The N-terminal EH domains are paired EF-hand/S100-like folds that recognize NPF and FW motifs in partner proteins through a conserved hydrophobic pocket, mediating interactions with synaptojanin, AP180, and stonin2 and thereby linking EPS15 to clathrin assembly and vesicle endocytosis (PMID:9721102, PMID:10471276, PMID:10757979, PMID:12807910, PMID:18200045). EPS15 is itself a substrate and effector of EGFR signaling: it is tyrosine-phosphorylated by the receptor, with phosphorylation at Tyr-850 specifically required for ligand-induced EGFR internalization but dispensable for constitutive transferrin uptake (PMID:7689153, PMID:10953014). EGF stimulation also drives monoubiquitination of EPS15, dependent on its second UIM, and its UIM domains read ubiquitinated cargo to recruit it for internalization; this ubiquitin-reading function extends to substrates including Cx43, AMPAR-GluA1, occludin, and NaV1.7 (PMID:9162018, PMID:12072436, PMID:15383614, PMID:19835873, PMID:25023288, PMID:33636390). EPS15 ubiquitination is tuned by parkin and the CUL3-SPOPL ligase and reversed by the deubiquitinase USP9X, coupling its activity to EGFR trafficking dynamics (PMID:16862145, PMID:26748853, PMID:27008177). Beyond the plasma membrane, EPS15 acts at the trans-Golgi network through AP-1 binding to support secretory exit, while endosomal isoforms diversify its function: Eps15b binds the ESCRT-0 component Hrs to promote EGFR degradation, whereas the short Eps15S isoform localizes to Rab11 recycling endosomes and directs EGFR recycling (PMID:18362181, PMID:18524853, PMID:21832070). EPS15 and its paralog EPS15L1 are redundantly essential for transferrin receptor endocytosis and embryonic development, with combined loss causing embryonic lethality and a cell-autonomous defect in iron internalization that produces microcytic hypochromic anemia (PMID:30692166).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1993 High

    Established EPS15 as a bona fide substrate of the EGF receptor kinase, providing the first link between this protein and growth factor signaling.

    Evidence Expression cloning with in vitro kinase and NIH 3T3 transformation assays

    PMID:7689153

    Open questions at the time
    • Did not identify the phosphorylation site or its functional consequence
    • Did not place EPS15 in any defined cellular pathway
  2. 1995 High

    Connected EPS15 to clathrin-mediated endocytosis by showing constitutive association with the AP-2 adaptor complex, redirecting its role from signaling to membrane traffic.

    Evidence Reciprocal co-IP, GST pull-down, and N-terminal sequencing of co-precipitated adaptins

    PMID:8557749

    Open questions at the time
    • Did not map the AP-2-binding region
    • Did not establish a functional requirement in endocytosis
  3. 1995 Medium

    Defined the EH domain as a discrete protein-interaction module, providing the conceptual basis for how EPS15 engages partner proteins.

    Evidence Domain mapping, filter-binding assays, and cloning with an EH domain probe

    PMID:7568168

    Open questions at the time
    • Did not identify the EH ligand motif
    • No structural detail of binding
  4. 1996 High

    Localized EPS15 to the rim of coated pits rather than uniformly with AP-2, implying a specific role at the site of pit invagination.

    Evidence Immunofluorescence, immunoelectron microscopy, and subcellular fractionation

    PMID:8910509

    Open questions at the time
    • Did not explain mechanistically why rim localization matters
    • Did not resolve EPS15 fate during vesicle budding
  5. 1997 Medium

    Mapped the AP-2-binding determinants to the C-terminus and the alpha-adaptin ear, and showed EGF-induced monoubiquitination as a second covalent modification distinct from phosphorylation.

    Evidence GST pull-down deletion mapping; western blotting and protein sequencing with internalization block

    PMID:9000562 PMID:9162018

    Open questions at the time
    • Did not identify the ubiquitin ligase or acceptor site
    • Did not establish functional role of ubiquitination
  6. 1997 Medium

    Demonstrated that EPS15 is functionally required for endocytosis and identified EH-domain ligands, linking EPS15 to the clathrin machinery and the synaptic vesicle cycle.

    Evidence Anti-EPS15 antibody microinjection internalization assays; NPF-motif binding of synaptojanin; oligomerization mapping

    PMID:9049247 PMID:9182572 PMID:9407958 PMID:9428629

    Open questions at the time
    • Antibody microinjection lacks domain-level resolution
    • Coiled-coil oligomerization role in vivo not defined
  7. 1998 High

    Established that the EPS15/AP-2 interaction is functionally required for receptor endocytosis and that EH domains recognize NPF motifs through a defined EF-hand fold, while EPS15 dissociates from AP-2 during coat assembly.

    Evidence Dominant-negative GFP fusions plus cell-free coat formation; NMR structure of EH2 with mutagenesis; in vitro coat assembly and native vesicle analysis

    PMID:9442014 PMID:9490719 PMID:9721102

    Open questions at the time
    • Mechanism coupling clathrin addition to EPS15 release not fully defined
    • In vivo relevance of EPS15 exclusion from vesicles inferred
  8. 1999 High

    Showed that EPS15 is essential for coated-pit assembly and AP-2 docking, and that its phosphorylation state regulates AP-2 binding, integrating regulatory control into the endocytic cycle.

    Evidence EH-deletion dominant-negative imaging and transferrin uptake; mitotic/synaptic phosphorylation binding assays; EH1 NMR structure; EGFR-induced relocalization

    PMID:10194409 PMID:10471276 PMID:9920862 PMID:9950686

    Open questions at the time
    • Kinases responsible for AP-2-modulating phosphorylation not all identified
    • Destination of relocalized EPS15 endocytic compartments incompletely defined
  9. 2000 High

    Identified Tyr-850 phosphorylation as a cargo-specific switch required for EGFR but not transferrin receptor internalization, and resolved EH-domain ligand discrimination structurally.

    Evidence Y850F mutagenesis with dominant-negative and phosphopeptide inhibition; EH3 NMR structure with FW/NPF mutagenesis; collaborative CCP targeting deletion analysis

    PMID:10652316 PMID:10757979 PMID:10953014

    Open questions at the time
    • Identity of the Tyr-850 phosphotyrosine-binding partner not determined
    • How cargo-specificity is wired to phosphorylation unresolved
  10. 2002 Medium

    Extended EPS15 function beyond the plasma membrane by demonstrating AP-1 binding at the Golgi and a CRM1-dependent nuclear export signal, and defined UIM2 as required for monoubiquitination.

    Evidence Gamma-appendage crystal structure; NES/CRM1 binding with leptomycin B; UIM mutational ubiquitination assays

    PMID:11777906 PMID:12072436 PMID:12176391

    Open questions at the time
    • Functional significance of nuclear export not established
    • Golgi role only structurally implied at this stage
  11. 2003 High

    Showed EPS15 actively stimulates clathrin assembly via EH-NPF interactions with AP180, providing a mechanistic role in coated-pit nucleation at synapses.

    Evidence In vitro clathrin assembly assay with peptide inhibition and squid nerve terminal injection

    PMID:12807910

    Open questions at the time
    • Quantitative contribution to pit nucleation in mammalian cells not measured
  12. 2004 Medium

    Demonstrated that c-Cbl ubiquitin ligase activity and the EPS15 UIM together direct EGFR into an ubiquitin-dependent, EPS15-mediated endocytic route.

    Evidence c-Cbl and EPS15 UIM mutant analysis with immunofluorescence recruitment assays

    PMID:15383614

    Open questions at the time
    • Did not resolve whether UIM reads cargo ubiquitin or EPS15 self-ubiquitination for recruitment
  13. 2006 High

    Identified parkin as an E3 ligase whose ubiquitination of EPS15 inhibits UIM binding to ubiquitinated EGFR, providing a regulatory brake on receptor internalization.

    Evidence Co-IP, ubiquitination assay, and EGFR endocytosis assay in parkin-KO cells

    PMID:16862145

    Open questions at the time
    • Physiological contexts where parkin regulates EPS15 not broadly defined
  14. 2007 High

    Genetic loss-of-function in worms and flies established EPS15 as required for synaptic vesicle endocytosis and identified direct partners (dynamin, Dap160/intersectin, SGIP1) at coated pits.

    Evidence C. elegans and Drosophila null mutants with epistasis, live imaging, and co-IP of mammalian partners

    PMID:11483962 PMID:17620409 PMID:17626015

    Open questions at the time
    • Redundancy with paralogs not addressed in single-organism mutants
  15. 2008 High

    Revealed isoform- and adaptor-specific diversification: Eps15b/Hrs promotes EGFR degradation, AP-1 binding supports TGN secretion, and EH2 binds stonin2 with high affinity via a dual-NPF mode.

    Evidence Isoform-specific knockdown and binding; AP-1 co-IP from Golgi fractions with secretion assay; NMR/ITC of EH2-stonin2

    PMID:18200045 PMID:18362181 PMID:18524853

    Open questions at the time
    • How isoform expression is regulated not defined
    • Distinct in vivo roles of plasma-membrane vs endosomal pools incompletely separated
  16. 2009 Medium

    Broadened the cargo repertoire by showing UIM-dependent recognition of ubiquitinated Cx43 (Nedd4-driven), and structurally defined how parkin's Ubl engages both EPS15 UIMs.

    Evidence Co-IP and siRNA of Nedd4/EPS15; NMR and mutagenesis of parkin Ubl-UIM interfaces

    PMID:19835873 PMID:19875440

    Open questions at the time
    • Met receptor recruitment route (coiled-coil/Grb2) distinctness needs broader validation
  17. 2011 Medium

    Showed that the short Eps15S isoform at Rab11 recycling endosomes diverts EGFR to recycling rather than degradation, defining a sorting-decision role for EPS15 isoforms.

    Evidence Isoform identification and siRNA knockdown/rescue with EGFR trafficking and Rab11 co-localization

    PMID:21832070

    Open questions at the time
    • Molecular basis for recycling versus degradative sorting by the isoform not resolved
  18. 2013 Medium

    Identified p38-mediated Ser-796 phosphorylation and AP-2-independent roles in EPEC pedestal formation, expanding the regulatory and functional contexts of EPS15.

    Evidence In vitro p38alpha kinase assay with site mapping; dominant-negative and siRNA in EPEC-infected cells

    PMID:21810914 PMID:24269888

    Open questions at the time
    • Functional consequence of Ser-796 phosphorylation not defined
    • Mechanism of AP-2-independent recruitment unclear
  19. 2016 High

    Provided structural and cell-biological mechanism for FCHO1/2-dependent decoding of EPS15 DPF triads in productive AP-2 assembly, and identified CUL3-SPOPL as an endosomal regulator of EPS15 levels and EGFR degradation.

    Evidence Crystal structure of EPS15/R-Fcho1 mu-homology complex with FCHO1/2-null cells and AP-2 assembly assays; SPOPL depletion with substrate MS and trafficking/morphology analysis

    PMID:27008177 PMID:27237791

    Open questions at the time
    • How DPF decoding integrates with EH-domain cargo capture during a single pit not resolved
  20. 2019 High

    Established EPS15/EPS15L1 functional redundancy as essential for transferrin receptor endocytosis, embryonic development, and iron homeostasis, defining the physiological core function.

    Evidence Constitutive and conditional double-knockout mice with transplantation and iron homeostasis assays

    PMID:30692166

    Open questions at the time
    • Tissue-specific non-redundant roles of each paralog not fully delineated
  21. 2021 Medium

    Demonstrated that UIM-dependent EPS15 recognition extends to additional ubiquitinated cargoes (NaV1.7 via a CRMP2/Numb/Nedd4-2 complex and occludin via ITCH), with disease-relevant functional readouts.

    Evidence siRNA knockdown with electrophysiology and knock-in mouse for NaV1.7; co-IP, knockdown rescue, and endothelial barrier assays for occludin

    PMID:33478555 PMID:33636390

    Open questions at the time
    • Whether EPS15 directly versus indirectly binds these cargoes in each complex not fully resolved
    • Generalizability across cell types untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple regulatory inputs (Tyr-850, Ser-796, monoubiquitination, FCHO-decoded DPF arrays) and the distinct isoforms are integrated to make cargo-specific and sorting-fate decisions at single coated structures remains unresolved.
  • No unified model linking phosphorylation, ubiquitination, and adaptor decoding at one pit
  • Quantitative kinetics of EPS15 recruitment/release during a single endocytic event not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 5 GO:0060090 molecular adaptor activity 4
Localization
GO:0005768 endosome 3 GO:0005886 plasma membrane 3 GO:0005794 Golgi apparatus 2 GO:0005829 cytosol 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-9609507 Protein localization 3 R-HSA-162582 Signal Transduction 2
Complex memberships
AP-1 clathrin adaptor complexAP-2 clathrin adaptor complexESCRT-0 (HRS/STAM)

Evidence

Reading pass · 50 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 Eps15 is a substrate of the EGF receptor kinase; EGFR directly phosphorylates Eps15 on tyrosine in vitro and in vivo, and overexpression of Eps15 transforms NIH 3T3 cells, implicating it in mitogenic signaling. Expression cloning, in vitro kinase assay, NIH 3T3 transformation assay Molecular and cellular biology High 7689153
1995 Eps15 is constitutively associated with the plasma membrane clathrin adaptor complex AP-2 (alpha- and beta-adaptins), suggesting a role in clathrin-mediated endocytosis. Co-immunoprecipitation with anti-Eps15 antibody, GST pull-down, N-terminal sequencing of co-precipitated proteins The Journal of cell biology High 8557749
1995 The EH (Eps15 Homology) domain, spanning ~70 amino acids in the N-terminus of Eps15, is a protein-protein interaction module that binds cytosolic proteins; a related protein, Eps15R, was identified using an EH domain probe. Domain mapping, filter-binding assays, cDNA cloning with EH domain probe Proceedings of the National Academy of Sciences of the United States of America Medium 7568168
1995 The Crk SH3 domain binds specifically to a conserved proline-rich P-X-L-P-X-K motif in Eps15, and Crk can facilitate stable association of Eps15 with activated EGFR in vitro. Expression library screen, co-precipitation from cell lysates, in vitro binding with translated proteins The Journal of biological chemistry Medium 7797522
1996 Eps15 localizes to the rim/edge of clathrin-coated pits and budding coated vesicles (not uniformly distributed like AP-2), and virtually all cellular Eps15 is associated with AP-2 in a complex unaffected by EGF treatment. Immunofluorescence microscopy, immunoelectron microscopy, subcellular fractionation The Journal of biological chemistry High 8910509
1997 Eps15 is monoubiquitinated upon EGF stimulation, representing a second form of EGF-induced covalent modification distinct from tyrosine phosphorylation; ubiquitination but not tyrosine phosphorylation was inhibited when EGF receptor internalization was blocked. Western blotting, protein sequencing, inhibition of receptor internalization The Journal of biological chemistry Medium 9162018
1997 The AP-2 binding region of Eps15 maps to its C-terminal ~80 amino acids with at least three determinants (residues 650-660, 680-690, 720-730), and AP-2 binds Eps15 through the C-terminal ear domain (alpha-ear) of its alpha-adaptin subunit. GST fusion protein pull-downs, deletion/mutation mapping Cancer research Medium 9000562
1997 Microinjection of antibodies against Eps15 and Eps15R inhibits internalization of EGF and transferrin, demonstrating that both are essential components of the endocytic machinery. Antibody microinjection, receptor internalization assays Cancer research Medium 9407958
1997 Eps15 is constitutively oligomerized via its central coiled-coil region (residues 321-520); large Eps15 oligomers co-immunoprecipitate with AP-2 more efficiently than dimers. Chemical cross-linking, size-exclusion chromatography, GST fusion domain mapping The Journal of biological chemistry Medium 9182572
1997 Synaptojanin-170 binds Eps15 through three NPF (Asn-Pro-Phe) repeats in its C-terminal region, interacting with the EH domains of Eps15, and synaptojanin 1 is concentrated at clathrin-coated endocytic intermediates in nerve terminals. In vitro binding assay, immunolocalization FEBS letters Medium 9428629
1997 EGF receptor activation leads to tyrosine phosphorylation of Eps15 in a receptor-specific manner (PDGF and insulin do not phosphorylate it); the cytoplasmic regulatory domain of EGFR is essential for Eps15 binding, and Eps15 is present in plasma membrane and endosomal fractions but not early endosomes (Rab4/Rab5-negative). Co-immunoprecipitation, subcellular fractionation, immunofluorescence with truncated EGFR mutants The Journal of cell biology Medium 9049247
1998 Overexpression of the AP-2-binding C-terminal domain of Eps15 (fused to GFP) strongly inhibits transferrin and EGF endocytosis; the inhibition requires intact AP-2-binding sites, demonstrating that AP-2/Eps15 interaction is required for receptor-mediated endocytosis. GFP fusion protein overexpression, transferrin/EGF internalization assays, cell-free coated vesicle formation assay with GST fusion proteins The Journal of cell biology High 9490719
1998 The structure of the central EH domain (EH2) of Eps15 was solved by NMR; it consists of a pair of EF-hand motifs (the second binds calcium), and NPF peptide binds in a hydrophobic pocket between two alpha-helices via a critical aromatic interaction confirmed by structure-based mutagenesis. Heteronuclear NMR spectroscopy, structure-based mutagenesis Science High 9721102
1998 During clathrin coat assembly in vitro, Eps15 dissociates from AP-2; coated vesicles isolated from brain do not contain detectable Eps15, suggesting that clathrin addition at the growing pit rim releases Eps15 from AP-2. In vitro clathrin-AP-2 coat assembly assay, immunoisolation of brain-derived coated vesicles The Journal of biological chemistry Medium 9442014
1999 An Eps15 mutant lacking EH domains causes loss of AP-2 and clathrin punctate distribution at the plasma membrane, redistribution of dynamin, and strong inhibition of transferrin endocytosis, indicating Eps15 is required for coated pit assembly and AP-2 docking at the plasma membrane. GFP-Eps15 mutant overexpression, immunofluorescence, transferrin uptake assay Journal of cell science High 10194409
1999 Upon EGFR activation, Eps15 undergoes dramatic relocalization: first to the plasma membrane, then to intracellular endocytic compartments (excluding coated vesicles), with tyrosine phosphorylation occurring both at the plasma membrane and in a nocodazole-sensitive compartment; relocalization is independent of direct EGFR binding or AP-2 binding. Immunofluorescence, immunoelectron microscopy, nocodazole treatment Molecular biology of the cell Medium 9950686
1999 The EH domain-mediated interaction between Eps15 and Hrb (HIV Rev cofactor) connects the endocytic machinery to nucleocytoplasmic transport; Eps15 and Eps15R synergize with Hrb to enhance Rev-mediated export, and this requires EH-mediated association occurring in the cytoplasm. Co-immunoprecipitation, Rev export functional assay, localization studies The Journal of cell biology Medium 10613896
1999 Mitotic phosphorylation of Eps15 inhibits its binding to the appendage domain of alpha-adaptin (AP-2); in nerve terminals, Eps15 undergoes constitutive phosphorylation and depolarization-dependent dephosphorylation, with dephosphorylation enhancing AP-2 binding in brain extracts. Phosphorylation state analysis, in vitro binding assay, synaptosome stimulation experiments The Journal of biological chemistry Medium 9920862
1999 The EH1 domain of Eps15 adopts a paired EF-hand fold similar to S100 proteins; an NPF-containing peptide from RAB binds in a hydrophobic pocket formed by conserved Trp and Leu residues. Multidimensional heteronuclear NMR spectroscopy, peptide binding studies Biochemistry High 10471276
2000 Tyrosine phosphorylation of Eps15 at Tyr-850 is required for EGFR internalization but not for constitutive transferrin receptor endocytosis; a phosphorylation-negative Eps15 mutant acts as dominant negative specifically on EGFR endocytosis, and phosphotyrosine in Eps15 serves as a docking site for a phosphotyrosine-binding protein. Site-directed mutagenesis (Y850F), dominant-negative overexpression, phosphopeptide inhibition assays The Journal of cell biology High 10953014
2000 CCP targeting of Eps15 requires collaboration between EH domains and AP-2-binding sites in the C-terminus; neither EH domains alone, the coiled-coil domain, nor the AP-2-binding domain alone are sufficient for CCP targeting; AP-2 binding sites are critical for plasma membrane localization. GFP-Eps15 deletion mutant transfection, immunofluorescence, transferrin uptake flow cytometry The Journal of biological chemistry Medium 10652316
2000 NMR structure of the third EH domain (EH3) of Eps15 reveals that both FW and NPF sequences bind in the same hydrophobic pocket; EH3 binds calcium in the first EF-hand (unlike EH2); point mutations alter preference for FW vs. NPF motifs. NMR spectroscopy, chemical shift mapping, point mutagenesis, peptide binding assays Biochemistry High 10757979
2000 Hrs-2 physically interacts with Eps15 in a calcium-dependent manner inhibited by SNAP-25 and alpha-adaptin; this interaction regulates receptor-mediated endocytosis, placing Hrs-2 in a biochemical pathway Hrs-2→Eps15→AP-2. Co-immunoprecipitation, in vitro binding, endocytosis inhibition assay, immunoelectron microscopy The Journal of biological chemistry Medium 10809762
2001 The C. elegans Eps15 ortholog EHS-1 localizes to synaptic regions; ehs-1-impaired worms show depletion of synaptic vesicles and neurotransmission defects; genetic interaction with dynamin mutant dyn-1 worsens locomotion defects, and mammalian Eps15 and dynamin interact in vivo. C. elegans genetics, epistasis with dynamin mutant, co-immunoprecipitation of mammalian proteins, immunolocalization Nature cell biology High 11483962
2002 The second UIM (ubiquitin-interacting motif) of Eps15 and Eps15R is essential for their monoubiquitination; the UIM does not contain the ubiquitin acceptor site but functions as a recruitment site for the ubiquitination machinery. UIM deletion/mutation analysis, ubiquitination assays in cells The Journal of biological chemistry Medium 12072436
2002 The gamma-adaptin appendage domain binds Eps15 at the same site as gamma-synergin; crystal structure of the gamma-appendage defines this binding surface, revealing that Eps15 is a ligand of AP-1 at the Golgi. 1.8 Å crystal structure, point mutation binding analysis Structure High 12176391
2002 Eps15 contains a leucine-rich nuclear export signal (NES) in its last ~25 amino acids that binds exportin CRM1 in a leucine-dependent manner; this NES prevents nuclear accumulation of Eps15, contrasting with Eps15R which lacks such a signal and is constitutively nuclear. GFP-Eps15 deletion mutants, leptomycin B treatment, CRM1 binding assay The Journal of biological chemistry Medium 11777906
2003 Eps15 stimulates AP180-mediated clathrin assembly in vitro via EH domain–NPF motif interactions; peptides from AP180 NPF sites block this stimulatory activity; injection of these peptides into squid giant nerve terminals inhibits clathrin-coated pit formation during synaptic vesicle endocytosis. In vitro clathrin assembly assay, peptide inhibition, squid nerve terminal injection The Journal of biological chemistry High 12807910
2004 c-Cbl ubiquitin ligase activity is required for EGF-induced recruitment of Eps15 to the plasma membrane; this recruitment requires the UIM of Eps15, identifying ubiquitin as a module directing EGFR into an Eps15-dependent endocytic pathway. c-Cbl mutant overexpression, Eps15 UIM mutant analysis, immunofluorescence Journal of cell science Medium 15383614
2005 Ubiquilin (hPLIC1) interacts with Eps15 via a UIM1–UBL domain interaction; UIM1 of Eps15 binds the UBL domain of ubiquilin but not ubiquitinated proteins, while UIM2 binds ubiquitinated proteins; ubiquilin recruits Eps15 to cytoplasmic ubiquitin-rich aggregates/aggresomes in a UIM-dependent manner. Yeast two-hybrid, GST pull-down, immunofluorescence co-localization Journal of cell science Medium 16159959
2006 Parkin binds Eps15 through its ubiquitin-like (Ubl) domain interacting with Eps15's UIMs; EGF stimulation promotes parkin-mediated ubiquitination of Eps15; parkin-mediated Eps15 ubiquitination interferes with Eps15 UIM binding to ubiquitinated EGFR, thereby delaying EGFR internalization. Co-immunoprecipitation, ubiquitination assay, EGFR endocytosis assay in parkin-KO cells Nature cell biology High 16862145
2007 Eps15 and Dap160/intersectin interact directly (Dap160 is a major Eps15 binding partner); Drosophila eps15-null mutants show reduced synaptic vesicle endocytosis and synaptic bouton defects; eps15/dap160 double mutants show additive endocytic defects, indicating they function in concert. Null mutant generation, synaptic vesicle endocytosis assay, genetic double-mutant epistasis, live imaging of Eps15 movement The Journal of cell biology High 17620409
2007 SGIP1alpha binds directly to Eps15 and colocalizes with Eps15 and AP-2 at clathrin-coated pits; SGIP1alpha overexpression reduces transferrin and EGF endocytosis. Co-immunoprecipitation, immunofluorescence co-localization, endocytosis assay The Journal of biological chemistry Medium 17626015
2008 The second EH domain (EH2) of Eps15 binds stonin2 with sub-micromolar affinity; NMR solution structure of the EH2–stonin2 complex shows the first NPF motif binds the conserved site while the second NPF inserts into a novel hydrophobic pocket, explaining high-affinity and selective binding. NMR solution structure, isothermal titration calorimetry, mutagenesis The EMBO journal High 18200045
2008 An endosomally-localized Eps15 isoform, Eps15b, directly binds the ESCRT-0 component Hrs and localizes to Hrs-positive endosomal microdomains; depletion of Eps15b delays EGFR degradation and promotes recycling, whereas depletion of Eps15 has no effect on EGFR degradation. Isoform cloning, in vitro binding assay, siRNA knockdown, EGFR trafficking assays The Journal of cell biology High 18362181
2008 Eps15 interacts with AP-1 at the trans-Golgi network; a 14-amino-acid motif near the AP-2-binding domain of Eps15 is required for AP-1 binding but not AP-2 binding; disruption of the Eps15-AP-1 interaction reduces secretory protein exit from the TGN. Co-immunoprecipitation from liver Golgi fractions, mutant Eps15 expression, siRNA knockdown of AP-1, secretion assay Molecular biology of the cell Medium 18524853
2008 Eps15 recruitment to the Met receptor tyrosine kinase requires its coiled-coil domain and the adaptor Grb2 (which binds via a proline-rich motif in Eps15 domain III), distinct from EGFR which requires the Eps15 UIM; Eps15 knockdown delays Met degradation, rescued by WT but not coiled-coil-deleted Eps15. Eps15 domain mutants, siRNA knockdown, co-immunoprecipitation, receptor degradation assays The Journal of biological chemistry Medium 19109251
2009 Eps15 interacts with ubiquitinated Cx43 through its UIM domain; Nedd4-mediated ubiquitination of Cx43 is required for Eps15 recruitment and subsequent endocytic trafficking of Cx43; Eps15 depletion causes accumulation of Cx43 at the plasma membrane. Co-immunoprecipitation, immunofluorescence, siRNA knockdown of Nedd4 and Eps15 Experimental cell research Medium 19835873
2009 The parkin Ubl domain uses distinct interaction surfaces to bind Eps15 UIMs vs. proteasomal subunit S5a UIMs; parkin binds both Eps15 UIMs to create a larger interaction surface including beta1 and beta2, whereas it preferentially binds UIM I of S5a using residue K48. NMR spectroscopy, site-directed mutagenesis The Journal of biological chemistry High 19875440
2011 Eps15S, a short splice isoform of Eps15 lacking 111 C-terminal amino acids, localizes to Rab11-positive recycling endosomes and promotes EGFR recycling back to the cell surface rather than lysosomal degradation; re-expression of Eps15S after knockdown reduces EGFR degradation and promotes recycling. RT-PCR identification of isoform, siRNA knockdown/rescue, EGFR trafficking assays, Rab11 co-localization The Journal of biological chemistry Medium 21832070
2012 Eps15 knockout mice show a 2-fold increase in marginal zone B cell numbers in a cell-autonomous manner; EPS15-KO hematopoietic precursors more efficiently repopulate B220+ bone marrow cells; this effect is independent of BCR signaling or Notch activity. Eps15 knockout mouse, competitive bone marrow transplantation, FACS analysis PloS one Medium 23226392
2013 Eps15 and Epsin1 (but not AP-2) are required for EPEC pedestal formation; clathrin-coated pit components Eps15 and epsin1 are recruited to EPEC infection sites independently of AP-2. Dominant-negative mutants, siRNA, immunofluorescence of infected cells The Journal of infectious diseases Medium 21810914
2013 p38 kinase directly phosphorylates Eps15 at Ser-796 upon EGF or TNF-alpha stimulation; recombinant p38alpha phosphorylates this residue in vitro. Phospho-specific mass spectrometry, kinase inhibitor treatment, in vitro kinase assay with recombinant p38alpha FEBS letters Medium 24269888
2014 Eps15 interacts with ubiquitinated AMPA receptors (GluA1) through its UIM domain; Nedd4-mediated GluA1 ubiquitination is required for the Eps15–AMPAR interaction; Eps15 knockdown suppresses ubiquitinated GluA1 internalization but not non-ubiquitinatable GluA1 mutant internalization. Co-immunoprecipitation, siRNA knockdown, surface expression assay, GluA1 ubiquitination-site mutant The Journal of biological chemistry Medium 25023288
2015 USP9X is a deubiquitinating enzyme for Eps15; USP9X depletion affects EGFR internalization and trafficking; Eps15 monoubiquitination occurs at low EGF doses and is essential for EGFR internalization; ubiquitination sites on Eps15 were mapped by systematic RNAi-based DUB screen. RNAi screen, EGFR trafficking assays, Eps15 ubiquitination site mapping Current biology Medium 26748853
2016 Arrayed DPF motifs within the Eps15/R C-terminus are differentially decoded by Fcho1/2 and AP-2; crystal structure of an Eps15/R–Fcho1 μ-homology domain complex reveals a spacing-dependent DPF triad bound in a mechanistically distinct mode from single DPF binding to AP-2; without Fcho1/2 and membrane-recruited Eps15, AP-2 assemblies are transient and endocytosis stalls. Crystal structure determination, cell lines lacking FCHO1/2, Eps15 membrane sequestration, AP-2 assembly assays Developmental cell High 27237791
2016 The CUL3-SPOPL E3 ubiquitin ligase complex ubiquitinates and degrades EPS15 at endosomes; EPS15 associates with the ESCRT-0 components HRS and STAM on endosomes; SPOPL depletion causes EPS15 and HRS accumulation, enlarged endosomes, impaired MVB formation, and defective EGFR degradation. SPOPL depletion, mass spectrometry substrate identification, EGFR trafficking assay, endosome morphology analysis eLife Medium 27008177
2019 EPS15 and EPS15L1 are redundantly required for transferrin receptor endocytosis and embryonic development; double knockout causes embryonic lethality; hematopoietic-specific double KO causes microcytic hypochromic anemia due to cell-autonomous defect in iron internalization (TfR endocytosis). Constitutive and conditional knockout mice, competitive bone marrow transplantation, iron homeostasis assays, embryonic lethality analysis Life science alliance High 30692166
2021 Non-SUMOylated CRMP2 forms a complex with Numb, Eps15, and Nedd4-2 to promote clathrin-mediated endocytosis of NaV1.7; silencing Eps15 in CRMP2K374A/K374A DRG neurons restores sodium currents, demonstrating that Eps15 is necessary for CRMP2-mediated NaV1.7 internalization. siRNA knockdown, NaV1.7 surface/current measurement, knock-in mouse model Molecular brain Medium 33478555
2021 Ubiquitinated occludin interacts with Eps15 through its UIM domain to initiate occludin internalization and trafficking to Rab5-positive vesicles for proteasomal degradation; ITCH E3 ligase ubiquitinates occludin and Eps15 knockdown rescues occludin degradation and endothelial barrier disruption caused by ALS SOD1 mutants. Co-immunoprecipitation, siRNA knockdown, surface localization assay, endothelial barrier assay Neurobiology of disease Medium 33636390

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Inhibition of clathrin-coated pit assembly by an Eps15 mutant. Journal of cell science 369 10194409
1998 AP-2/Eps15 interaction is required for receptor-mediated endocytosis. The Journal of cell biology 310 9490719
2006 A regulated interaction with the UIM protein Eps15 implicates parkin in EGF receptor trafficking and PI(3)K-Akt signalling. Nature cell biology 307 16862145
1993 eps15, a novel tyrosine kinase substrate, exhibits transforming activity. Molecular and cellular biology 252 7689153
1998 Intersectin, a novel adaptor protein with two Eps15 homology and five Src homology 3 domains. The Journal of biological chemistry 239 9813051
1996 Eps15 is a component of clathrin-coated pits and vesicles and is located at the rim of coated pits. The Journal of biological chemistry 222 8910509
1998 Pan1p, yeast eps15, functions as a multivalent adaptor that coordinates protein-protein interactions essential for endocytosis. The Journal of cell biology 207 9531549
1996 A novel fluorescence-activated cell sorter-based screen for yeast endocytosis mutants identifies a yeast homologue of mammalian eps15. The Journal of cell biology 202 8978817
1999 The EH and SH3 domain Ese proteins regulate endocytosis by linking to dynamin and Eps15. The EMBO journal 189 10064583
1998 Dap160, a neural-specific Eps15 homology and multiple SH3 domain-containing protein that interacts with Drosophila dynamin. The Journal of biological chemistry 174 9668096
1997 eps15 and eps15R are essential components of the endocytic pathway. Cancer research 173 9407958
1995 The tyrosine kinase substrate eps15 is constitutively associated with the plasma membrane adaptor AP-2. The Journal of cell biology 156 8557749
2000 Epsin 1 undergoes nucleocytosolic shuttling and its eps15 interactor NH(2)-terminal homology (ENTH) domain, structurally similar to Armadillo and HEAT repeats, interacts with the transcription factor promyelocytic leukemia Zn(2)+ finger protein (PLZF). The Journal of cell biology 144 10791968
2001 Yeast Eps15-like endocytic protein, Pan1p, activates the Arp2/3 complex. Nature cell biology 138 11433303
1997 Synaptojanin 1: localization on coated endocytic intermediates in nerve terminals and interaction of its 170 kDa isoform with Eps15. FEBS letters 134 9428629
1995 A protein-binding domain, EH, identified in the receptor tyrosine kinase substrate Eps15 and conserved in evolution. Proceedings of the National Academy of Sciences of the United States of America 131 7568168
1994 A novel gene, AF-1p, fused to HRX in t(1;11)(p32;q23), is not related to AF-4, AF-9 nor ENL. Oncogene 118 8134107
1999 The interaction of epsin and Eps15 with the clathrin adaptor AP-2 is inhibited by mitotic phosphorylation and enhanced by stimulation-dependent dephosphorylation in nerve terminals. The Journal of biological chemistry 114 9920862
1997 Association and colocalization of Eps15 with adaptor protein-2 and clathrin. The Journal of cell biology 113 9049247
2000 Tyrosine phosphorylation of Eps15 is required for ligand-regulated, but not constitutive, endocytosis. The Journal of cell biology 111 10953014
1998 Structure and Asn-Pro-Phe binding pocket of the Eps15 homology domain. Science (New York, N.Y.) 111 9721102
2007 Eps15 and Dap160 control synaptic vesicle membrane retrieval and synapse development. The Journal of cell biology 108 17620409
2009 Eps15 interacts with ubiquitinated Cx43 and mediates its internalization. Experimental cell research 100 19835873
2000 Mapping of Eps15 domains involved in its targeting to clathrin-coated pits. The Journal of biological chemistry 97 10652316
1999 Eps15 is recruited to the plasma membrane upon epidermal growth factor receptor activation and localizes to components of the endocytic pathway during receptor internalization. Molecular biology of the cell 97 9950686
1997 Epidermal growth factor induces ubiquitination of Eps15. The Journal of biological chemistry 92 9162018
2004 A JC virus-induced signal is required for infection of glial cells by a clathrin- and eps15-dependent pathway. Journal of virology 89 14671106
2002 A ubiquitin-interacting motif (UIM) is essential for Eps15 and Eps15R ubiquitination. The Journal of biological chemistry 88 12072436
1997 Mapping of the molecular determinants involved in the interaction between eps15 and AP-2. Cancer research 88 9000562
1995 The SH3 domain of Crk binds specifically to a conserved proline-rich motif in Eps15 and Eps15R. The Journal of biological chemistry 87 7797522
2016 Transient Fcho1/2⋅Eps15/R⋅AP-2 Nanoclusters Prime the AP-2 Clathrin Adaptor for Cargo Binding. Developmental cell 84 27237791
1999 Epidermal growth factor pathway substrate 15, Eps15. The international journal of biochemistry & cell biology 84 10481267
2002 The Eps15 homology (EH) domain. FEBS letters 80 11911876
1999 Chlamydia infection of epithelial cells expressing dynamin and Eps15 mutants: clathrin-independent entry into cells and dynamin-dependent productive growth. Journal of cell science 76 10212143
2009 Eps15 homology domain 1-associated tubules contain phosphatidylinositol-4-phosphate and phosphatidylinositol-(4,5)-bisphosphate and are required for efficient recycling. Molecular biology of the cell 75 19369419
2002 Gamma-adaptin appendage domain: structure and binding site for Eps15 and gamma-synergin. Structure (London, England : 1993) 72 12176391
2015 USP9X Controls EGFR Fate by Deubiquitinating the Endocytic Adaptor Eps15. Current biology : CB 71 26748853
2009 Eps15: a multifunctional adaptor protein regulating intracellular trafficking. Cell communication and signaling : CCS 69 19814798
2008 An endosomally localized isoform of Eps15 interacts with Hrs to mediate degradation of epidermal growth factor receptor. The Journal of cell biology 67 18362181
1999 Clathrin, adaptors and eps15 in endosomes containing activated epidermal growth factor receptors. Journal of cell science 64 9885285
2001 The Eps15 C. elegans homologue EHS-1 is implicated in synaptic vesicle recycling. Nature cell biology 58 11483962
2005 Ubiquilin recruits Eps15 into ubiquitin-rich cytoplasmic aggregates via a UIM-UBL interaction. Journal of cell science 57 16159959
2003 Eps15 homology domain-NPF motif interactions regulate clathrin coat assembly during synaptic vesicle recycling. The Journal of biological chemistry 57 12807910
2000 Hrs-2 regulates receptor-mediated endocytosis via interactions with Eps15. The Journal of biological chemistry 57 10809762
2016 A SPOPL/Cullin-3 ubiquitin ligase complex regulates endocytic trafficking by targeting EPS15 at endosomes. eLife 54 27008177
2007 SGIP1alpha is an endocytic protein that directly interacts with phospholipids and Eps15. The Journal of biological chemistry 54 17626015
2007 EHD1 and Eps15 interact with phosphatidylinositols via their Eps15 homology domains. The Journal of biological chemistry 53 17412695
1997 Eps15 is constitutively oligomerized due to homophilic interaction of its coiled-coil region. The Journal of biological chemistry 52 9182572
2002 Interactions of phocein with nucleoside-diphosphate kinase, Eps15, and Dynamin I. The Journal of biological chemistry 51 11872741
1998 Assembly of clathrin coats disrupts the association between Eps15 and AP-2 adaptors. The Journal of biological chemistry 50 9442014
2008 Mouse hepatitis virus type 2 enters cells through a clathrin-mediated endocytic pathway independent of Eps15. Journal of virology 48 18550663
2013 Differential roles of C-terminal Eps15 homology domain proteins as vesiculators and tubulators of recycling endosomes. The Journal of biological chemistry 47 24019528
2004 Ubiquitin ligase activity of c-Cbl guides the epidermal growth factor receptor into clathrin-coated pits by two distinct modes of Eps15 recruitment. The Journal of biological chemistry 46 15465819
2011 Recycling of the epidermal growth factor receptor is mediated by a novel form of the clathrin adaptor protein Eps15. The Journal of biological chemistry 45 21832070
1998 EAST, an epidermal growth factor receptor- and Eps15-associated protein with Src homology 3 and tyrosine-based activation motif domains. The Journal of biological chemistry 44 9694904
1999 The eps15 homology (EH) domain-based interaction between eps15 and hrb connects the molecular machinery of endocytosis to that of nucleocytosolic transport. The Journal of cell biology 43 10613896
1994 The human eps15 gene, encoding a tyrosine kinase substrate, is conserved in evolution and maps to 1p31-p32. Oncogene 43 8183552
2004 c-Cbl directs EGF receptors into an endocytic pathway that involves the ubiquitin-interacting motif of Eps15. Journal of cell science 41 15383614
2006 Negative regulation of yeast Eps15-like Arp2/3 complex activator, Pan1p, by the Hip1R-related protein, Sla2p, during endocytosis. Molecular biology of the cell 38 17151356
2010 Mechanism for the selective interaction of C-terminal Eps15 homology domain proteins with specific Asn-Pro-Phe-containing partners. The Journal of biological chemistry 37 20106972
2008 Eps15 mediates vesicle trafficking from the trans-Golgi network via an interaction with the clathrin adaptor AP-1. Molecular biology of the cell 37 18524853
1997 The localization of the HRX/ALL1 protein to specific nuclear subdomains is altered by fusion with its eps15 translocation partner. Cancer research 36 9041173
2002 Differential nucleocytoplasmic trafficking between the related endocytic proteins Eps15 and Eps15R. The Journal of biological chemistry 35 11777906
2005 The Troyer syndrome (SPG20) protein spartin interacts with Eps15. Biochemical and biophysical research communications 29 16036216
2008 Structure of the Eps15-stonin2 complex provides a molecular explanation for EH-domain ligand specificity. The EMBO journal 27 18200045
2008 Distinct recruitment of Eps15 via Its coiled-coil domain is required for efficient down-regulation of the met receptor tyrosine kinase. The Journal of biological chemistry 27 19109251
2000 Hydrogen peroxide reversibly inhibits epidermal growth factor (EGF) receptor internalization and coincident ubiquitination of the EGF receptor and Eps15. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27 11156945
1999 The EH1 domain of Eps15 is structurally classified as a member of the S100 subclass of EF-hand-containing proteins. Biochemistry 25 10471276
2021 Non-SUMOylated CRMP2 decreases NaV1.7 currents via the endocytic proteins Numb, Nedd4-2 and Eps15. Molecular brain 24 33478555
2020 Sorting nexin 17 (SNX17) links endosomal sorting to Eps15 homology domain protein 1 (EHD1)-mediated fission machinery. The Journal of biological chemistry 24 32041776
2017 Increased Eps15 homology domain 1 and RAB11FIP3 expression regulate breast cancer progression via promoting epithelial growth factor receptor recycling. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 24 28215104
2021 Lineage Switch in an Infant B-Lymphoblastic Leukemia With t(1;11)(p32;q23); KMT2A/EPS15, Following Blinatumomab Therapy. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 23 33749383
2014 Endocytic adaptor epidermal growth factor receptor substrate 15 (Eps15) is involved in the trafficking of ubiquitinated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. The Journal of biological chemistry 22 25023288
1998 EH domain-dependent interactions between Eps15 and clathrin-coated vesicle protein p95. Biochemical and biophysical research communications 22 9535728
2019 Mammalian Eps15 homology domain 1 potentiates angiogenesis of non-small cell lung cancer by regulating β2AR signaling. Journal of experimental & clinical cancer research : CR 21 31023336
2016 EHD3 Protein Is Required for Tubular Recycling Endosome Stabilization, and an Asparagine-Glutamic Acid Residue Pair within Its Eps15 Homology (EH) Domain Dictates Its Selective Binding to NPF Peptides. The Journal of biological chemistry 21 27189942
2009 Differential interaction of the E3 ligase parkin with the proteasomal subunit S5a and the endocytic protein Eps15. The Journal of biological chemistry 21 19875440
2000 Solution structure of Eps15's third EH domain reveals coincident Phe-Trp and Asn-Pro-Phe binding sites. Biochemistry 20 10757979
2007 Binding to DPF-motif by the POB1 EH domain is responsible for POB1-Eps15 interaction. BMC biochemistry 19 18154663
1995 Expression of the receptor tyrosine kinase substrate genes eps8 and eps15 during mouse development. Oncogene 17 7566980
2023 Upregulation of CSNK1A1 induced by ITGB5 confers to hepatocellular carcinoma resistance to sorafenib in vivo by disrupting the EPS15/EGFR complex. Pharmacological research 16 37149115
2011 Eps15 and Epsin1 are crucial for enteropathogenic Escherichia coli pedestal formation despite the absence of adaptor protein 2. The Journal of infectious diseases 16 21810914
2011 Regulation of clathrin coat assembly by Eps15 homology domain-mediated interactions during endocytosis. Molecular biology of the cell 16 22190739
2020 Eps15 Homology Domain Protein 4 (EHD4) is required for Eps15 Homology Domain Protein 1 (EHD1)-mediated endosomal recruitment and fission. PloS one 15 32966336
2012 The endocytic adaptor Eps15 controls marginal zone B cell numbers. PloS one 15 23226392
2006 Drosophila homologue of Eps15 is essential for synaptic vesicle recycling. Experimental cell research 15 16709407
1995 Structural requirements of the epidermal growth factor receptor for tyrosine phosphorylation of eps8 and eps15, substrates lacking Src SH2 homology domains. The Journal of biological chemistry 15 7608194
2019 Redundant and nonredundant organismal functions of EPS15 and EPS15L1. Life science alliance 14 30692166
2017 Mammalian Eps15 homology domain 1 promotes metastasis in non-small cell lung cancer by inducing epithelial-mesenchymal transition. Oncotarget 14 27531895
2016 Yeast Eps15-like endocytic protein Pan1p regulates the interaction between endocytic vesicles, endosomes and the actin cytoskeleton. eLife 14 26914139
2013 p38-Mediated phosphorylation of Eps15 endocytic adaptor protein. FEBS letters 14 24269888
2013 Scratching the surface: actin' and other roles for the C-terminal Eps15 homology domain protein, EHD2. Histology and histopathology 14 24347515
2015 Eps15 homology domain containing protein of Plasmodium falciparum (PfEHD) associates with endocytosis and vesicular trafficking towards neutral lipid storage site. Biochimica et biophysica acta 13 26284889
2014 UIM domain-dependent recruitment of the endocytic adaptor protein Eps15 to ubiquitin-enriched endosomes. BMC cell biology 13 25260758
2022 Circular RNA Eps15-homology domain containing protein 2 motivates proliferation, glycolysis but refrains autophagy in non-small cell lung cancer via crosstalk with microRNA-3186-3p and forkhead box K1. Bioengineered 12 35220908
2015 Eps15 Homology Domain-containing Protein 3 Regulates Cardiac T-type Ca2+ Channel Targeting and Function in the Atria. The Journal of biological chemistry 12 25825486
2022 Circular RNA Eps15-homology domain-containing protein 2 induce resistance of renal cell carcinoma to sunitinib via microRNA-4731-5p/ABCF2 axis. Bioengineered 11 35412955
2003 Ligand-induced clathrin-mediated endocytosis of the keratinocyte growth factor receptor occurs independently of either phosphorylation or recruitment of eps15. FEBS letters 11 14572635
2021 ALS-causing SOD1 mutants regulate occludin phosphorylation/ubiquitination and endocytic trafficking via the ITCH/Eps15/Rab5 axis. Neurobiology of disease 10 33636390
2018 Eps15 homology domain 1 promotes the evolution of papillary thyroid cancer by regulating endocytotic recycling of epidermal growth factor receptor. Oncology letters 10 30214560

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