Affinage

EHD1

EH domain-containing protein 1 · UniProt Q9H4M9

Length
534 aa
Mass
60.6 kDa
Annotated
2026-04-28
100 papers in source corpus 46 papers cited in narrative 46 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EHD1 is an ATP-dependent membrane fission enzyme that oligomerizes on phosphatidylserine-enriched endosomal tubules to catalyze vesicle scission, thereby controlling exit of diverse cargo—including transferrin receptor, MHC-I, integrins, GLUT4, EGFR, IGF-1R, and PD-L1—from recycling endosomes back to the plasma membrane (PMID:30518883, PMID:16445686, PMID:12032069, PMID:40703029). Its C-terminal EH domain recruits EHD1 to membranes through dual recognition of NPF-motif partners (MICAL-L1, Rabenosyn-5, Syndapin2) and direct phosphatidylinositol binding, while the N-terminal P-loop ATPase domain drives scaffold assembly and membrane thinning that leads to fission of tubules below ~25 nm radius (PMID:17412695, PMID:19864458, PMID:30518883, PMID:15020713). Beyond endocytic recycling, EHD1 functions in ciliogenesis by tubulating preciliary membranes at distal appendage vesicles and delivering the E3 ligase HERC2 to the mother centriole to ubiquitinate CP110, and its loss in mice causes neural tube defects with deregulated Hedgehog signaling (PMID:25686250, PMID:37074924, PMID:26884322). A homozygous missense mutation (p.R398W) in EHD1 causes autosomal recessive tubular proteinuria, sensorineural deafness, and male infertility in humans and mouse models (PMID:35149593, PMID:37900275).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 Medium

    Identification of EHD1 as an EH-domain protein on endocytic vesicles established the gene's entry into endosomal trafficking biology and revealed its domain architecture (P-loop, coiled-coil, EH domain).

    Evidence GFP-fusion live imaging and Northern analysis in cultured cells

    PMID:10395801

    Open questions at the time
    • No function assigned beyond localization
    • ATPase activity of the P-loop not tested
    • No interacting partners identified
  2. 2002 High

    Demonstration that EHD1 associates with Arf6-containing tubules and is required for clathrin-independent recycling of MHC-I established EHD1 as a functional regulator of endosomal membrane tubulation and receptor recycling, with both the P-loop and EH domain being essential.

    Evidence Domain mutagenesis, MHC-I recycling assays, and dominant-negative Arf6 experiments in HeLa cells

    PMID:12032069 PMID:12121420

    Open questions at the time
    • Mechanism of tubule formation (motor vs. scaffold) unknown
    • ATPase catalytic cycle not characterized
  3. 2004 High

    Mapping of the EH domain as a hub that binds NPF-motif partners (Rabenosyn-5, EHBP1) and epistasis experiments positioned EHD1 downstream of Rab4/Rab5-dependent sorting and implicated it in recycling of diverse cargo including GLUT4.

    Evidence GST pulldown with mass spectrometry, domain mapping, sequential RNAi epistasis, insulin-stimulated GLUT4 recycling assays

    PMID:15020713 PMID:15247266

    Open questions at the time
    • Direct membrane-binding mechanism of EHD1 not resolved
    • Whether EHD1 performs fission or stabilizes tubules unclear
  4. 2006 High

    EHD1 knockout mice confirmed the in vivo requirement for EHD1 in exit of cargo from recycling endosomes, validating cell-based findings genetically.

    Evidence Transferrin recycling assays in EHD1 knockout mouse embryonic fibroblasts

    PMID:16445686

    Open questions at the time
    • Organismal phenotypes beyond MEF recycling not yet characterized
    • Redundancy with other EHD family members not addressed
  5. 2007 High

    Multiple studies expanded EHD1's cargo repertoire to β1-integrins and cholesterol/LDL, linked EHD1 to retromer-dependent endosome-to-Golgi retrieval, and solved the EH domain NMR structure revealing a phosphoinositide-binding surface distinct from the NPF pocket.

    Evidence EHD1 KO MEFs with integrin recycling and cholesterol assays; comparative proteomics identifying retromer interaction; NMR structure and PI-binding mutagenesis (K483)

    PMID:17284518 PMID:17412695 PMID:17451652 PMID:17868075 PMID:17899392

    Open questions at the time
    • Full-length EHD1 structure not determined
    • Mechanism of membrane scission vs. stabilization still unresolved
    • Relative contribution of PI binding vs. NPF-partner binding to membrane recruitment unknown
  6. 2009 High

    MICAL-L1 was identified as the key adaptor that recruits EHD1 (and Rab8a) to tubular recycling endosomes, and reconstitution of an amphiphysin–EHD1 (AMPH-1–RME-1) complex showed it generates morphologically distinct coated membrane tubules, providing the first in vitro evidence of cooperative membrane remodeling.

    Evidence Purified-protein membrane tubulation assay (C. elegans proteins), C. elegans genetics, human BIN1 knockdown; MICAL-L1 Co-IP and siRNA with recycling assays

    PMID:19864458 PMID:19915558

    Open questions at the time
    • Reconstitution with human EHD1 not yet performed
    • Scission activity not demonstrated in this system
  7. 2010 High

    EHD1 knockout revealed essential roles in spermatogenesis (acrosome development) and showed that EHD1 and EHD4 form endogenous heteromers whose balance regulates neuronal L1/NgCAM endocytosis, broadening EHD1's physiological roles beyond generic recycling.

    Evidence EHD1 KO mouse histopathology and EM for spermatogenesis; shRNA and oligomerization mutants for neuronal trafficking

    PMID:20359371 PMID:20463227 PMID:21147988

    Open questions at the time
    • Mechanism of EHD1 in acrosome biogenesis not defined at molecular level
    • Stoichiometry of EHD1–EHD4 complexes unknown
  8. 2015 High

    EHD1 was shown to function in ciliogenesis—tubulating preciliary membranes at distal appendage vesicles and enabling ciliary vesicle formation—and its membrane recruitment was found to depend on phosphatidylserine flipping by the P4-ATPase ATP8A1, establishing PS asymmetry as a prerequisite for EHD1 engagement.

    Evidence siRNA, EM of centriole structures, transition zone protein localization for ciliogenesis; ATP8A1 depletion with PS distribution and EHD1 localization assays

    PMID:25595798 PMID:25686250

    Open questions at the time
    • How EHD1 senses PS enrichment at the molecular level unclear
    • Whether ATP hydrolysis is required for ciliogenesis-specific function not tested
  9. 2016 High

    EHD1 knockout on a C57BL/6 background caused embryonic lethality with neural tube defects, short cilia, and deregulated Hedgehog signaling, establishing EHD1 as essential for developmental Hedgehog pathway output and identifying Smoothened as a direct binding partner.

    Evidence EHD1 KO mouse, immunohistochemistry, Co-IP for Smoothened, ciliary length measurement, GLI3 repressor quantification

    PMID:26884322

    Open questions at the time
    • Mechanism by which EHD1 regulates Smoothened ciliary entry not defined
    • Tissue-specific versus universal requirement for EHD1 in Hedgehog signaling not resolved
  10. 2018 High

    In vitro reconstitution on supported membrane tubes demonstrated that EHD1 is a bona fide ATP-dependent membrane fission enzyme: ATP-bound EHD1 scaffolds thin membranes and ATP hydrolysis drives self-assembly leading to scission of tubes below 25 nm radius, directly resolving the long-standing question of whether EHD1 stabilizes or severs tubules.

    Evidence Supported membrane tube assay, molecular dynamics simulation, N-terminal deletion mutagenesis, C. elegans cross-complementation

    PMID:30403133 PMID:30518883

    Open questions at the time
    • Full atomic structure of the membrane-bound oligomer lacking
    • Regulation of ATPase cycle by partners (MICAL-L1, GRAF1) not reconstituted
  11. 2022 High

    A human founder mutation p.R398W in EHD1 was identified as the cause of autosomal recessive tubular proteinuria and sensorineural deafness, validated in KO and knockin mice showing impaired proximal tubule endocytosis and defective spermatogenesis with loss of VPS35/retromer co-localization.

    Evidence Patient genetics, Ehd1 KO and R398W knockin mice, zebrafish model, proximal tubule endocytosis assays, VPS35 co-localization

    PMID:35149593 PMID:37900275

    Open questions at the time
    • Structural basis of R398W destabilization only modeled in silico
    • Whether hearing loss is due to ciliary or recycling defect not determined
  12. 2023 High

    The ciliogenesis mechanism was further refined: EHD1 transports HERC2-containing centriolar satellites to the mother centriole to ubiquitinate CP110, providing a molecular link between EHD1's membrane trafficking function and centriole remodeling during cilia initiation.

    Evidence siRNA, Co-IP, ubiquitination assays, centriolar satellite tracking

    PMID:37074924

    Open questions at the time
    • Whether HERC2 transport is dependent on EHD1 ATPase activity not tested
    • Interplay between HERC2 and MIB1 at the centriole not fully resolved
  13. 2025 Medium

    EHD1 was shown to promote PD-L1 recycling to the cell surface; its depletion diverted PD-L1 to lysosomal degradation and enhanced anti-tumor T cell cytotoxicity, extending EHD1's cargo repertoire to immune checkpoint regulation.

    Evidence Co-IP, PD-L1 internalization/recycling assays, MeRIP-qPCR for m6A modification, immunocompetent mouse tumor model

    PMID:40703029

    Open questions at the time
    • Direct structural basis of EHD1–PD-L1 interaction not defined
    • Generalizability across tumor types not established
    • m6A regulation of EHD1 mRNA awaits independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the high-resolution structure of the full-length membrane-bound EHD1 oligomer, the regulatory logic by which distinct NPF-motif partners select cargo-specific fission events, and the mechanism by which EHD1 ATPase activity is coordinated with partner proteins (GRAF1, MICAL-L1, BIN1) during scission.
  • No high-resolution structure of full-length EHD1 on membranes
  • How cargo specificity is encoded by different NPF adaptors is undefined
  • ATPase regulation by partner proteins not reconstituted in vitro

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 2 GO:0016787 hydrolase activity 2 GO:0140657 ATP-dependent activity 2
Localization
GO:0005768 endosome 7 GO:0031410 cytoplasmic vesicle 5 GO:0005815 microtubule organizing center 3 GO:0005929 cilium 3 GO:0005886 plasma membrane 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 8 R-HSA-1852241 Organelle biogenesis and maintenance 4 R-HSA-9609507 Protein localization 4 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3
Partners
BIN1EHBP1EHD3EHD4MICAL-L1RABENOSYN-5SNAP29SNX17

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 EHD1 was identified as an EH domain-containing protein that localizes to transferrin-containing endocytic vesicles in cultured cells, with predicted protein structure including an N-terminal nucleotide-binding P-loop, central coiled-coil domain, and C-terminal EH domain with EF/Ca2+-binding motif. GFP-fusion protein live imaging, Northern analysis, immunostaining Genomics Medium 10395801
2001 EHD1 directly interacts with SNAP29 and associates with alpha-adaptin of the AP-2 complex and IGF-1R; overexpression of EHD1 represses IGF-1-mediated MAPK and Akt phosphorylation, indicating EHD1 acts as a downregulator of IGF-1R signaling. Co-immunoprecipitation, co-localization, overexpression with downstream signaling readouts (MAPK/Akt phosphorylation) The Journal of biological chemistry Medium 11423532
2002 EHD1 associates with Arf6-containing membrane tubules and induces tubule formation to facilitate recycling of MHC-I molecules internalized via clathrin-independent endocytosis; the N-terminal P-loop domain and C-terminal EH domain are both required for tubule association and formation. Overexpression of tagged EHD1 and domain mutants, immunofluorescence, MHC-I recycling assays, dominant-negative Arf6 experiments The EMBO journal High 12032069
2002 EHD1 and EHD3 interact with each other (confirmed by yeast two-hybrid and co-immunoprecipitation), and the N-terminal domain of EHD3 is responsible for its tubular localization; coexpression of EHD1 and EHD3 results in their co-localization in microtubule-dependent tubules. Yeast two-hybrid, co-immunoprecipitation, GFP-fusion live imaging, domain-swap chimeras Traffic (Copenhagen, Denmark) High 12121420
2004 EHD1 interacts with the divalent Rab4/Rab5 effector Rabenosyn-5 via its EH domain binding to the first two NPF motifs of Rabenosyn-5; Rabenosyn-5 acts sequentially before EHD1 in transport from early endosomes to the endosomal recycling compartment and back to the plasma membrane. GST-pulldown from brain cytosol, mass spectrometry, domain mapping, immunofluorescence, RNAi knockdown with transferrin and MHC-I recycling assays, epistasis by double RNAi Molecular biology of the cell High 15020713
2004 EHD1 interacts via its EH domain with EHBP1 and controls perinuclear localization of GLUT4-containing membranes; EHD1 is required for insulin-stimulated GLUT4 recycling to the plasma membrane in adipocytes. Co-immunoprecipitation, dominant-negative expression (ΔEH-EHD1), siRNA knockdown, immunofluorescence, glucose transport assays The Journal of biological chemistry High 15247266
2004 EHD1 interacts with GS32/SNAP-29 via its EH domain binding to the N-terminal NPF-containing region of GS32, and with syndapin II via the EH domain; these two interactions are mutually exclusive, suggesting EHD1 participates in pathways of both GS32 and syndapin II in a mutually exclusive manner. GST pulldown from cell extracts and brain extracts, co-immunoprecipitation, competition binding assays Molecular membrane biology Medium 15371016
2006 EHD1 knockout mice exhibit delayed recycling of transferrin to the plasma membrane with accumulation in the endocytic recycling compartment, confirming EHD1's role in exit of membrane proteins from recycling endosomes in vivo. EHD1 knockout mouse model, transferrin uptake and recycling assays in embryonic fibroblasts Traffic (Copenhagen, Denmark) High 16445686
2007 EHD1 directly binds phosphatidylinositols, preferring those phosphorylated at position 3; the EH domain's Lys-483 residue (on the face opposite to the NPF-binding pocket) is critical for phosphatidylinositol binding, as determined by 2D NMR. In vitro phospholipid binding assays, 2D NMR analysis, site-directed mutagenesis (K483) The Journal of biological chemistry High 17412695
2007 EHD1 interacts with retromer in vivo, colocalizes with retromer, and stabilizes SNX1-positive tubules; loss of EHD1 by RNAi destabilizes SNX1 tubules and inhibits endosome-to-Golgi retrieval of CIMPR; P-loop mutation of EHD1 causes dominant-negative effects on retromer localization. Comparative proteomics (endosomal fractions from WT vs retromer-deficient cells), co-immunoprecipitation, RNAi, P-loop dominant-negative mutant, CIMPR trafficking assays Traffic (Copenhagen, Denmark) High 17868075
2007 EHD1 regulates beta1 integrin endosomal recycling; RNAi knockdown of EHD1 impairs beta1 integrin recycling, EHD1-knockout MEFs show impaired cell spreading and migration on fibronectin and slower focal adhesion disassembly, phenotypes rescued by wild-type EHD1 re-expression. RNAi knockdown, EHD1 knockout MEFs, integrin recycling assays, focal adhesion analysis, migration and spreading assays, rescue with wild-type EHD1 Journal of cell science High 17284518
2007 EHD1 regulates cholesterol homeostasis; EHD1 knockout MEFs display reduced esterified and free cholesterol, smaller lipid droplets, and ineffectual cholesterol uptake via LDL receptor, reversed by wild-type but not dysfunctional EHD1. EHD1 knockout MEFs, cholesterol measurement assays, lipid droplet quantification, LDL receptor internalization, siRNA, rescue with WT vs. mutant EHD1 Biochemical and biophysical research communications High 17451652
2007 EHD1 localizes to a tubular network containing EHD3 and Rab8a; Myosin Vb interacts with Rab8a (confirmed by yeast two-hybrid and FRET) and colocalizes with EHD1/EHD3-positive Rab8a tubules, defining a recycling pathway distinct from the Rab11a pathway. Yeast two-hybrid, FRET imaging, co-localization immunofluorescence, dominant-negative Myosin Vb expression Molecular biology of the cell Medium 17507647
2007 The solution structure of the EHD1 EH domain was solved by NMR; it resembles the second N-terminal EH domain of Eps15 but shows differences in surface charge and the NPF/DPF-binding pocket structure. NMR spectroscopy, backbone resonance assignment, solution structure determination Journal of biomolecular NMR High 17899392
2008 EHD1 undergoes serine phosphorylation that is enhanced by serum stimulation; PKC is one of the kinases responsible; inhibitors of clathrin-mediated endocytosis (but not caveolin-mediated endocytosis) decrease EHD1 phosphorylation, placing phosphorylation between early endosomes and the endocytic recycling compartment. Phosphorylation assays, kinase inhibitor treatments, endocytosis pathway inhibitors Cellular & molecular biology letters Medium 18661112
2009 C. elegans AMPH-1 (Amphiphysin/BIN1 ortholog) colocalizes with RME-1 (EHD1 ortholog) on recycling endosomes; AMPH-1 NPF motifs bind the RME-1 EH domain; purified AMPH-1-RME-1 complexes produce short coated membrane tubules distinct from those by either protein alone; BIN1 is required for EHD1-regulated endocytic recycling in human cells. In vivo C. elegans co-localization, deletion mutant analysis, in vitro membrane tubulation with purified proteins, human BIN1 knockdown with EHD1 recycling assays Nature cell biology High 19915558
2009 MICAL-L1 interacts with EHD1 via its NPF motifs and the EHD1 EH domain, recruits both EHD1 and Rab8a to tubular recycling endosomes; MICAL-L1 depletion causes loss of EHD1-Rab8a interaction and absence of both proteins from membrane tubules, impairing endocytic recycling. Co-immunoprecipitation, in vitro binding, live cell imaging, siRNA depletion with recycling assays, colocalization studies Molecular biology of the cell High 19864458
2010 EHD1 interacts directly with Fer1L5 (via Fer1L5's second C2 domain); EHD1 (and EHD2) knockdown inhibits myoblast fusion; EHD2 is required for normal translocation of Fer1L5 to the plasma membrane. Direct binding assays, siRNA knockdown, myoblast fusion quantification, plasma membrane translocation assays The Journal of biological chemistry Medium 21177873
2010 EHD1 knockout male mice are infertile due to defective spermatogenesis: abnormal acrosomal development, clumping of acrosomes, misaligned spermatids, absence of elongated spermatids, and abnormal phagocytosis of elongated spermatids by Sertoli cells. EHD1 knockout mouse model (Cre/loxP), histopathology, in situ hybridization, immunohistochemistry, light and electron microscopy BMC developmental biology High 20359371
2010 EHD1 regulates early transport of the GPI-anchored protein CD59 from pre-sorting endosomes to the endocytic recycling compartment; EHD1 depletion causes rapid Rab5-independent coalescence of CD59 at the ERC in a PKC-dependent manner. siRNA depletion, dominant-negative Arf6 expression, PKC inhibitor (Go6976) treatment, immunofluorescence Traffic (Copenhagen, Denmark) Medium 20961375
2010 EHD1 is required for proper L1/NgCAM endocytosis and recycling in neurons; EHD1 colocalizes with L1/NgCAM predominantly in EEA1-positive early endosomes; EHD1 knockdown delays L1/NgCAM exit from EEA1-positive endosomes and impairs its axonal targeting. shRNA knockdown, live imaging, co-localization with compartment markers, EEA1-positive endosome exit assays The Journal of neuroscience Medium 21147988
2010 Balanced levels of EHD1 and EHD4 are required for L1/NgCAM endocytosis in neurons; EHD1 overexpression impairs NgCAM internalization (but not transferrin); EHD1 oligomerization is required for this endocytosis defect; an endogenous EHD1-EHD4 complex was identified. shRNA knockdown, overexpression of EHD family members, endocytosis assays, oligomerization mutants The Journal of neuroscience Medium 20463227
2010 EHD1 interacts with snapin via its EH domain and negatively affects SNAP-25 binding to snapin; EHD1 overexpression reduces depolarization-induced exocytosis in PC12 cells, but this is not observed with an N-terminal EHD1 construct unable to bind snapin. Yeast two-hybrid, co-immunoprecipitation, binding competition assay, electrophysiological exocytosis measurement in PC12 cells Molecular and cellular neurosciences Medium 20696250
2012 Retrograde trafficking of Shiga toxin B (STxB) from recycling endosome to TGN requires EHD1; EHD1 is not significantly required for CI-M6PR retrograde trafficking; retromer is required for exit from early endosomes to recycling endosomes for both cargoes. RNAi knockdown of EHD1 and retromer components, STxB and CI-M6PR trafficking assays, ablation of recycling endosome Traffic (Copenhagen, Denmark) Medium 22540229
2012 EHD1 and cPLA2α interact in vivo (proximity <40 nm) and co-depletion experiments show both are involved in vesiculation of GPI-AP (CD59)-containing endosomes; cPLA2α depletion causes hypertubulation of CD59 endosomes and EHD1 depletion phenocopies this; lysophospholipid accumulation drives vesiculation. siRNA depletion, proximity ligation assay, co-immunoprecipitation, lysophospholipid acyltransferase inhibitor treatment, immunofluorescence Molecular biology of the cell Medium 22456504
2012 Rabankyrin-5 interacts with EHD1 via its EH domain and the NPFED motif of Rank-5; Rank-5 also colocalizes with retromer component Vps26 and is required for normal retromer distribution and CIMPR retrieval to Golgi; depletion of either Rank-5 or EHD1 impairs VSVG secretion. GST-pulldown, yeast two-hybrid, isothermal calorimetry, co-immunoprecipitation, siRNA depletion, CIMPR and VSVG trafficking assays Traffic (Copenhagen, Denmark) High 22284051
2014 EHD1 mediates vesicle trafficking required for normal muscle growth; EHD1-null myoblasts have defective receptor recycling and mislocalization of caveolin-3 and Fer1L5; EHD1 localizes to T-tubules in wildtype skeletal muscle and its loss causes T-tubule overgrowth and excess vesicle accumulation; EHD1 ATPase domain is required for tubule formation in myoblasts. EHD1 knockout mouse model, immunofluorescence, electron microscopy, ATPase domain mutant expression, myoblast fusion quantification, BIN1-induced tubulation assays Developmental biology High 24440153
2014 GRAF1 forms a complex with EHD1 and MICAL-L1; GRAF1 overexpression vesiculates MICAL-L1-containing tubular recycling endosomes, while GRAF1 depletion impairs TRE vesiculation and delays receptor recycling; co-addition of purified EHD1 and GRAF1 synergistically produces TRE vesiculation in semi-permeabilized cells. Co-immunoprecipitation, semi-permeabilized cell vesiculation assay with purified proteins, siRNA depletion, overexpression, immunofluorescence Frontiers in cell and developmental biology Medium 25364729
2014 MICAL-L1 and EHD1 regulate cytokinesis; depletion of either protein increases binucleated cells due to impaired recycling endosome transport during late cytokinesis; MICAL-L1 (but not EHD1) also regulates chromosome alignment during early mitosis and microtubule dynamics. siRNA depletion, binucleation quantification, live cell imaging, chromosome alignment analysis Traffic (Copenhagen, Denmark) Medium 25287187
2014 EHD1 is required for Src trafficking and activation; MICAL-L1 recruits EHD1 to Src-containing recycling endosomes in response to growth factor stimulation, and EHD1 (along with MICAL-L1) is required for growth-factor- and integrin-induced Src activation, focal adhesion turnover, cell spreading and migration. siRNA depletion, co-localization, co-immunoprecipitation, Src activation assays, focal adhesion analysis, migration assays Journal of cell science Medium 24481818
2015 EHD1 and EHD3 function in early ciliogenesis: they localize to preciliary membranes/ciliary pocket, mediate membrane tubulation essential for ciliary vesicle formation from distal appendage vesicles (DAVs), and are required for mother centriole to basal body transformation, transition zone protein and IFT20 recruitment; SNAP29 (EHD1-binding protein) is also required for DAV-mediated ciliary vesicle assembly. siRNA depletion, live cell imaging, SNAP29 knockdown, electron microscopy of centriole structures, localization of transition zone proteins and IFT20 Nature cell biology High 25686250
2015 EHD1 recruitment to recycling endosomes requires PS flipping by the P4-ATPase ATP8A1; depletion of ATP8A1 disrupts asymmetric PS distribution in REs, dissociates EHD1 from REs, and generates aberrant endosomal tubules resistant to fission; EHD1 does not show membrane localization in cells defective in PS synthesis. siRNA depletion of ATP8A1, PS distribution assays, EHD1 localization analysis, endosomal tubule morphology by microscopy The EMBO journal High 25595798
2016 EHD1 localizes to primary cilia and centrosomes; EHD1 knockout in mice causes embryonic lethality with neural tube closure defects, short cilia on neuroepithelium, deregulated ciliary SHH signaling, downregulation of GLI3 repressor formation, and increased ventral neuronal markers; EHD1 co-localizes with Smoothened and co-traffics with Smoothened into primary cilia, and is identified as a direct binding partner of Smoothened. EHD1 knockout mouse (B6 background), immunohistochemistry, co-immunoprecipitation, live cell imaging, ciliary length measurement Scientific reports High 26884322
2018 EHD1 is an ATP-dependent membrane fission catalyst; ATP-bound EHD1 forms membrane-active scaffolds that bulge tubular model membranes; ATP hydrolysis promotes scaffold self-assembly causing membrane thinning and scission of tubes below 25 nm radius; deletion of N-terminal residues causes defects in scaffolding, scission and endocytic recycling; cross-complementation in C. elegans confirms membrane binding and ATP hydrolysis are necessary for recycling. Supported membrane tube assay, molecular dynamics simulations, C. elegans cross-complementation, N-terminal deletion mutagenesis, in vitro ATP hydrolysis assays Nature communications High 30518883
2018 Using a supported membrane tube scission screen, EHD1 was identified as a novel ATP-dependent membrane fission catalyst in brain cytosol; its GTP-dependent counterpart is dynamin. Supported membrane tube fission assay (microscopic screen), biochemical fractionation, mass spectrometric identification Biochemistry High 30403133
2019 MICAL-L1 coordinates EHD1 recruitment to the primary cilium; MICAL-L1 knockdown prevents CP110 removal from the mother centriole (similar to EHD1 knockdown) and prevents EHD1 localization to basal bodies; MICAL-L1 directly interacts with α/β-tubulin heterodimers and γ-tubulin, anchoring it to the centriole to recruit EHD1. siRNA depletion, mass spectrometry of MICAL-L1 interactors, direct interaction assays with tubulins, immunofluorescence Journal of cell science Medium 31615969
2019 EHD1 interacts with Cx43 (connexin 43) and regulates its internalization; EHD1 knockdown impairs Cx43 internalization and preserves gap junction-intercellular coupling; interaction is mediated by Eps15 and promoted by Cx43 phosphorylation and ubiquitination; EHD1 overexpression accelerates Cx43 internalization and exacerbates ischemia-induced Cx43 lateralization. Co-immunoprecipitation (Cx43-EHD1 interaction), siRNA knockdown, overexpression, gap junction coupling assay, ischemia model in isolated cardiomyocytes Circulation research Medium 32138615
2020 SNX17 directly interacts with EHD1; LRP1 internalization recruits cytoplasmic EHD1 to endosomal membranes; EHD1 depletion causes enlarged SNX17-containing endosomes, suggesting EHD1 catalyzes fission of SNX17-sorted receptor vesicles. Co-immunoprecipitation, in vitro binding assay, surface rendering quantification of EHD1/SNX17 overlap, EHD1 siRNA with endosome size measurement The Journal of biological chemistry Medium 32041776
2020 EHD4 is required for EHD1 recruitment to sorting endosomes; EHD4 preferentially dimerizes with EHD1; knockdown/knockout of EHD4 impairs EHD1 recruitment to sorting endosomes and causes enlarged SE; NPF-motif-containing partners Rabenosyn-5, Syndapin2 and MICAL-L1 are each required for EHD1 recruitment to SE. siRNA, shRNA and CRISPR/Cas9 EHD4 knockout, endosome size quantification, EHD1 localization assays, dimerization assays PloS one Medium 32966336
2020 EHD1 and RUSC2 control cell surface display and recycling of EGFR from the Golgi; EHD1 knockdown causes EGFR accumulation at the Golgi compartment, reducing surface EGFR and impairing EGF-induced proliferation; RUSC2 knockdown phenocopies EHD1 depletion. Inducible siRNA knockdown, surface EGFR quantification, immunofluorescence, EGF-induced proliferation assay, rescue with exogenous EHD1 Molecular and cellular biology Medium 31932478
2022 A human founder missense mutation p.R398W in EHD1 causes autosomal recessive tubular proteinuria and sensorineural deafness; patients and Ehd1 knockout/knockin mice show impaired receptor-mediated endocytosis in proximal tubules; in silico analysis predicts R398W destabilizes EHD1 structure and impairs nucleotide binding, likely reducing EHD1 oligomerization and membrane remodeling. Genetic mapping, patient clinical analysis, Ehd1 KO and knockin mouse models, zebrafish model, proximal tubule endocytosis assays, in silico structural analysis Journal of the American Society of Nephrology High 35149593
2022 Coronin2A (CORO2A) is a novel EHD1 interaction partner; CORO2A depletion causes enlarged endosomes and impaired recycling of clathrin-independent cargo, consistent with a role in EHD1-dependent endosomal fission. Co-immunoprecipitation, siRNA depletion, endosome size quantification, cargo recycling assays, actin protrusion analysis Molecular biology of the cell Medium 35921168
2023 EHD1 regulates CP110 ubiquitination during ciliogenesis by transporting centriolar satellites containing the E3 ubiquitin ligase HERC2 to the mother centriole; HERC2 and MIB1 both interact with and ubiquitinate CP110; HERC2 localizes to centriolar satellites and is required for ciliogenesis. siRNA depletion, co-immunoprecipitation, ubiquitination assays, centriolar satellite tracking, immunofluorescence EMBO reports High 37074924
2023 EHD1 is required for anterograde Golgi-to-plasma membrane traffic and endocytic recycling of IGF-1R in Ewing sarcoma; EHD1 overexpression-dependent oncogenic traits require IGF-1R expression and kinase activity; shRNA/CRISPR KO of EHD1 reduces tumorigenesis and metastasis. shRNA knockdown, CRISPR knockout with mouse Ehd1 rescue, RTK antibody arrays, surface IGF-1R quantification, tumor xenograft and metastasis assays Communications biology Medium 37474760
2023 The EHD1 p.R398W missense mutation causes male infertility in knockin mice with defective acrosomal development, missing sperm tail midpieces, and disorganized spermatogenic epithelium; wild-type EHD1 co-localizes with acrosomal granules and the retromer component VPS35, but the p.R398W mutant does not co-localize with VPS35. Knockin mouse model, histopathology, immunofluorescence co-localization (WT vs. R398W with VPS35 and acrosomal markers), electron microscopy Frontiers in cell and developmental biology High 37900275
2025 EHD1 interacts with PD-L1 protein and promotes PD-L1 endocytic recycling; EHD1 knockdown inhibits PD-L1 recycling and promotes its lysosomal degradation, enhancing T cell cytotoxicity; EHD1 mRNA is m6A-modified and YTHDF1 binds EHD1 mRNA to stabilize it in an m6A-dependent manner. Molecular docking, co-immunoprecipitation, immunofluorescence, receptor internalization/recycling assays, MeRIP-qPCR, RNA immunoprecipitation, m6A-binding site mutation analysis, immunocompetent mouse tumor model Cancer communications Medium 40703029

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 A tubular EHD1-containing compartment involved in the recycling of major histocompatibility complex class I molecules to the plasma membrane. The EMBO journal 264 12032069
2015 Early steps in primary cilium assembly require EHD1/EHD3-dependent ciliary vesicle formation. Nature cell biology 208 25686250
2008 Ehd2, a rice ortholog of the maize INDETERMINATE1 gene, promotes flowering by up-regulating Ehd1. Plant physiology 198 18790997
2016 Hd1,a CONSTANS ortholog in rice, functions as an Ehd1 repressor through interaction with monocot-specific CCT-domain protein Ghd7. The Plant journal : for cell and molecular biology 176 26991872
2007 OsMADS51 is a short-day flowering promoter that functions upstream of Ehd1, OsMADS14, and Hd3a. Plant physiology 171 17951465
2009 AMPH-1/Amphiphysin/Bin1 functions with RME-1/Ehd1 in endocytic recycling. Nature cell biology 167 19915558
2009 MICAL-L1 links EHD1 to tubular recycling endosomes and regulates receptor recycling. Molecular biology of the cell 149 19864458
2010 OsCOL4 is a constitutive flowering repressor upstream of Ehd1 and downstream of OsphyB. The Plant journal : for cell and molecular biology 144 20409004
2007 Myosin Vb interacts with Rab8a on a tubular network containing EHD1 and EHD3. Molecular biology of the cell 141 17507647
2004 Rabenosyn-5 and EHD1 interact and sequentially regulate protein recycling to the plasma membrane. Molecular biology of the cell 122 15020713
2015 Transport through recycling endosomes requires EHD1 recruitment by a phosphatidylserine translocase. The EMBO journal 114 25595798
2008 Rice Indeterminate 1 (OsId1) is necessary for the expression of Ehd1 (Early heading date 1) regardless of photoperiod. The Plant journal : for cell and molecular biology 113 18774969
2007 EHD1 interacts with retromer to stabilize SNX1 tubules and facilitate endosome-to-Golgi retrieval. Traffic (Copenhagen, Denmark) 112 17868075
2007 EHD1 regulates beta1 integrin endosomal transport: effects on focal adhesions, cell spreading and migration. Journal of cell science 110 17284518
2001 Association of insulin-like growth factor 1 receptor with EHD1 and SNAP29. The Journal of biological chemistry 108 11423532
2004 Role of EHD1 and EHBP1 in perinuclear sorting and insulin-regulated GLUT4 recycling in 3T3-L1 adipocytes. The Journal of biological chemistry 103 15247266
2015 Genetic interactions between diverged alleles of Early heading date 1 (Ehd1) and Heading date 3a (Hd3a)/ RICE FLOWERING LOCUS T1 (RFT1) control differential heading and contribute to regional adaptation in rice (Oryza sativa). The New phytologist 91 26096631
2014 Rice miR172 induces flowering by suppressing OsIDS1 and SNB, two AP2 genes that negatively regulate expression of Ehd1 and florigens. Rice (New York, N.Y.) 82 26224560
1999 EHD1--an EH-domain-containing protein with a specific expression pattern. Genomics 78 10395801
2016 Homodimerization of Ehd1 Is Required to Induce Flowering in Rice. Plant physiology 76 26864016
2002 EHD3: a protein that resides in recycling tubular and vesicular membrane structures and interacts with EHD1. Traffic (Copenhagen, Denmark) 74 12121420
2006 Recycling to the plasma membrane is delayed in EHD1 knockout mice. Traffic (Copenhagen, Denmark) 69 16445686
2020 EHD1 Modulates Cx43 Gap Junction Remodeling Associated With Cardiac Diseases. Circulation research 55 32138615
2007 Ectopic expression of OsLFL1 in rice represses Ehd1 by binding on its promoter. Biochemical and biophysical research communications 54 17592727
2019 EHD1 impairs decidualization by regulating the Wnt4/β-catenin signaling pathway in recurrent implantation failure. EBioMedicine 53 31707150
2016 A CONSTANS-like transcriptional activator, OsCOL13, functions as a negative regulator of flowering downstream of OsphyB and upstream of Ehd1 in rice. Plant molecular biology 53 27405463
2012 Retromer guides STxB and CD8-M6PR from early to recycling endosomes, EHD1 guides STxB from recycling endosome to Golgi. Traffic (Copenhagen, Denmark) 53 22540229
2007 EHD1 and Eps15 interact with phosphatidylinositols via their Eps15 homology domains. The Journal of biological chemistry 53 17412695
2010 The endocytic recycling regulator EHD1 is essential for spermatogenesis and male fertility in mice. BMC developmental biology 51 20359371
2010 Endocytic recycling proteins EHD1 and EHD2 interact with fer-1-like-5 (Fer1L5) and mediate myoblast fusion. The Journal of biological chemistry 51 21177873
2018 SIP1 participates in regulation of flowering time in rice by recruiting OsTrx1 to Ehd1. The New phytologist 50 29611871
2018 ATP-dependent membrane remodeling links EHD1 functions to endocytic recycling. Nature communications 50 30518883
2012 Rabankyrin-5 interacts with EHD1 and Vps26 to regulate endocytic trafficking and retromer function. Traffic (Copenhagen, Denmark) 49 22284051
2019 Targeting the IL-1β/EHD1/TUBB3 axis overcomes resistance to EGFR-TKI in NSCLC. Oncogene 47 31740781
2018 OsMFT1 increases spikelets per panicle and delays heading date in rice by suppressing Ehd1, FZP and SEPALLATA-like genes. Journal of experimental botany 46 30124949
2016 Hd3a, RFT1 and Ehd1 integrate photoperiodic and drought stress signals to delay the floral transition in rice. Plant, cell & environment 44 27111837
2014 EHD1 mediates vesicle trafficking required for normal muscle growth and transverse tubule development. Developmental biology 44 24440153
2012 cPLA2α and EHD1 interact and regulate the vesiculation of cholesterol-rich, GPI-anchored, protein-containing endosomes. Molecular biology of the cell 44 22456504
2011 Heading date gene, dth3 controlled late flowering in O. Glaberrima Steud. by down-regulating Ehd1. Plant cell reports 43 21830130
2007 EHD1 regulates cholesterol homeostasis and lipid droplet storage. Biochemical and biophysical research communications 41 17451652
2016 CONSTANS-like 9 (COL9) delays the flowering time in Oryza sativa by repressing the Ehd1 pathway. Biochemical and biophysical research communications 39 27620492
2004 Mutually exclusive interactions of EHD1 with GS32 and syndapin II. Molecular membrane biology 38 15371016
2014 GRAF1 forms a complex with MICAL-L1 and EHD1 to cooperate in tubular recycling endosome vesiculation. Frontiers in cell and developmental biology 36 25364729
2017 OsLBD37 and OsLBD38, two class II type LBD proteins, are involved in the regulation of heading date by controlling the expression of Ehd1 in rice. Biochemical and biophysical research communications 35 28342864
2007 EH domain of EHD1. Journal of biomolecular NMR 35 17899392
2010 Alterations of EHD1/EHD4 protein levels interfere with L1/NgCAM endocytosis in neurons and disrupt axonal targeting. The Journal of neuroscience : the official journal of the Society for Neuroscience 33 20463227
2016 Endocytic recycling protein EHD1 regulates primary cilia morphogenesis and SHH signaling during neural tube development. Scientific reports 32 26884322
2015 Both Hd1 and Ehd1 are important for artificial selection of flowering time in cultivated rice. Plant science : an international journal of experimental plant biology 32 26566836
2010 Neuronal early endosomes require EHD1 for L1/NgCAM trafficking. The Journal of neuroscience : the official journal of the Society for Neuroscience 30 21147988
2018 NF-κB-driven improvement of EHD1 contributes to erlotinib resistance in EGFR-mutant lung cancers. Cell death & disease 29 29549343
2022 A novel EHD1/CD44/Hippo/SP1 positive feedback loop potentiates stemness and metastasis in lung adenocarcinoma. Clinical and translational medicine 28 35485206
2020 OsRE1 interacts with OsRIP1 to regulate rice heading date by finely modulating Ehd1 expression. Plant biotechnology journal 28 32757315
2009 Drosophila Past1 is involved in endocytosis and is required for germline development and survival of the adult fly. Journal of cell science 27 19174465
2012 TNAP and EHD1 are over-expressed in bovine brain capillary endothelial cells after the re-induction of blood-brain barrier properties. PloS one 25 23119012
2019 MICAL-L1 coordinates ciliogenesis by recruiting EHD1 to the primary cilium. Journal of cell science 24 31615969
2021 A feedback circuit comprising EHD1 and 14-3-3ζ sustains β-catenin/c-Myc-mediated aerobic glycolysis and proliferation in non-small cell lung cancer. Cancer letters 23 34217785
2020 Sorting nexin 17 (SNX17) links endosomal sorting to Eps15 homology domain protein 1 (EHD1)-mediated fission machinery. The Journal of biological chemistry 23 32041776
2010 MICAL-L1: An unusual Rab effector that links EHD1 to tubular recycling endosomes. Communicative & integrative biology 23 20585517
2014 Novel functions for the endocytic regulatory proteins MICAL-L1 and EHD1 in mitosis. Traffic (Copenhagen, Denmark) 22 25287187
2016 EHD1 confers resistance to cisplatin in non-small cell lung cancer by regulating intracellular cisplatin concentrations. BMC cancer 21 27411790
2023 Exogenous abscisic acid represses rice flowering via SAPK8-ABF1-Ehd1/Ehd2 pathway. Journal of advanced research 19 37399924
2020 In-Frame and Frame-Shift Editing of the Ehd1 Gene to Develop Japonica Rice With Prolonged Basic Vegetative Growth Periods. Frontiers in plant science 19 32265960
2023 Improving yield-related traits by editing the promoter of the heading date gene Ehd1 in rice. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 18 37930441
2021 OsLHY is involved in regulating flowering through the Hd1- and Ehd1- mediated pathways in rice (Oryza sativa L.). Plant science : an international journal of experimental plant biology 18 35067308
2010 Pre-sorting endosomal transport of the GPI-anchored protein, CD59, is regulated by EHD1. Traffic (Copenhagen, Denmark) 18 20961375
2014 Regulation of Src trafficking and activation by the endocytic regulatory proteins MICAL-L1 and EHD1. Journal of cell science 17 24481818
2023 EHD1 promotes CP110 ubiquitination by centriolar satellite delivery of HERC2 to the mother centriole. EMBO reports 16 37074924
2015 The EHD protein Past1 controls postsynaptic membrane elaboration and synaptic function. Molecular biology of the cell 16 26202464
2015 Molecular dynamics simulation of the interactions between EHD1 EH domain and multiple peptides. Journal of Zhejiang University. Science. B 16 26465136
2014 Expression of TGFβ-1 and EHD1 correlated with survival of non-small cell lung cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 16 24946721
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
2018 A Screen for Membrane Fission Catalysts Identifies the ATPase EHD1. Biochemistry 15 30403133
2013 EHD1 functions in endosomal recycling and confers salt tolerance. PloS one 15 23342166
2010 EHD1 is a synaptic protein that modulates exocytosis through binding to snapin. Molecular and cellular neurosciences 15 20696250
1999 Evaluation and molecular characterization of EHD1, a candidate gene for Bardet-Biedl syndrome 1 (BBS1). Gene 15 10564830
2020 Engineering EHD1-Targeted Natural Borneol Nanoemulsion Potentiates Therapeutic Efficacy of Gefitinib against Nonsmall Lung Cancer. ACS applied materials & interfaces 13 32927941
2016 CSF-1 receptor signalling is governed by pre-requisite EHD1 mediated receptor display on the macrophage cell surface. Cellular signalling 13 27224507
2023 EHD1-dependent traffic of IGF-1 receptor to the cell surface is essential for Ewing sarcoma tumorigenesis and metastasis. Communications biology 12 37474760
2015 ARF-GEF cytohesin-2/ARNO regulates R-Ras and α5-integrin recycling through an EHD1-positive compartment. Molecular biology of the cell 12 26378252
2022 A Founder Mutation in EHD1 Presents with Tubular Proteinuria and Deafness. Journal of the American Society of Nephrology : JASN 11 35149593
2022 Coronin2A links actin-based endosomal processes to the EHD1 fission machinery. Molecular biology of the cell 11 35921168
2020 EHD1 and RUSC2 Control Basal Epidermal Growth Factor Receptor Cell Surface Expression and Recycling. Molecular and cellular biology 11 31932478
2022 EHD1 promotes the cancer stem cell (CSC)-like traits of glioma cells via interacting with CD44 and suppressing CD44 degradation. Environmental toxicology 10 35616188
2015 The endocytic recycling regulatory protein EHD1 Is required for ocular lens development. Developmental biology 10 26455409
2009 A model for the role of EHD1-containing membrane tubules in endocytic recycling. Communicative & integrative biology 9 19907710
2022 Entamoeba histolytica EHD1 Is Involved in Mitosome-Endosome Contact. mBio 8 35404118
2022 bZIP71 delays flowering by suppressing Ehd1 expression in rice. Journal of integrative plant biology 8 35546447
2015 Eps 15 Homology Domain (EHD)-1 Remodels Transverse Tubules in Skeletal Muscle. PloS one 8 26325203
2008 EHDS are serine phosphoproteins: EHD1 phosphorylation is enhanced by serum stimulation. Cellular & molecular biology letters 7 18661112
2024 Enhancing Yield and Improving Grain Quality in Japonica Rice: Targeted EHD1 Editing via CRISPR-Cas9 in Low-Latitude Adaptation. Current issues in molecular biology 5 38666963
2022 Interleukin-6 signaling requires EHD1-mediated alteration of membrane rafts. The FEBS journal 5 35429212
2016 The importance of EHD1 in neurite outgrowth contributing to the functional recovery after spinal cord injury. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 5 27211346
2025 m6A-modified EHD1 controls PD-L1 endosomal trafficking to modulate immune evasion and immunotherapy responses in lung adenocarcinoma. Cancer communications (London, England) 4 40703029
2018 Triad1 regulates the expression and distribution of EHD1 contributing to the neurite outgrowth of neurons after spinal cord injury. Journal of cellular biochemistry 4 30320922
2017 Thioether-stapled macrocyclic inhibitors of the EH domain of EHD1. Bioorganic & medicinal chemistry 4 28951093
2024 EHD1 promotes breast cancer metastasis through upregulating HIF2a expression via activating mTOR pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 3 39530565
2023 A missense mutation in Ehd1 associated with defective spermatogenesis and male infertility. Frontiers in cell and developmental biology 3 37900275
2022 Transcription factor bZIP65 delays flowering via suppressing Ehd1 expression in rice. Molecular breeding : new strategies in plant improvement 3 37313010
2024 EHD1 impaired decidualization of endometrial stromal cells in recurrent implantation failure: role of SENP1 in modulating progesterone receptor signalling†. Biology of reproduction 2 38011671
2020 Identification of phostensin in association with Eps 15 homology domain-containing protein 1 (EHD1) and EHD4. Biochemical and biophysical research communications 2 32800345