Affinage

EHD2

EH domain-containing protein 2 · UniProt Q9NZN4

Length
543 aa
Mass
61.2 kDa
Annotated
2026-06-09
49 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EHD2 is a dynamin-related ATPase that functions as the principal structural stabilizer of plasma membrane caveolae, controlling their dynamics and turnover and thereby gating a wide range of caveolae-dependent cellular processes (PMID:22323287, PMID:22505029). EHD2 dimers oligomerize into ring- and filament-shaped scaffolds on highly curved membranes, where ATP binding drives membrane insertion and an open conformation, oligomerization stabilizes caveolae and confines them to the cell surface, and ATP hydrolysis triggers EHD2 detachment [PMID:22505029, PMID:28223496, PMID:bio_10.1101_2025.06.05.658037]. Its membrane targeting is governed by an autoinhibitory N-terminus that folds into the GTPase domain and is released to wedge into the bilayer, by ATP binding, and by the anionic phospholipid PIP2, while an unstructured loop bearing NPF/KPF motifs directs both oligomerization and partner binding (PMID:24040268, PMID:24508342, PMID:28223496). At caveolae EHD2 cooperates with the structural components cavin1, caveolin-1, and the F-BAR protein pacsin2/syndapin2, occupying the caveolar body/neck while pacsin2 links the structure to the plasma membrane (PMID:22323287, PMID:35834519). By restricting caveolar internalization, EHD2 supports caveola-dependent fatty acid/CD36 uptake and adipocyte lipid handling (PMID:32170013, PMID:30811273), eNOS surface localization and nitric oxide signaling (PMID:31600286), sarcolemmal KATP channel and Orai1/SOCE surface expression (PMID:29133341, PMID:36625722), and Dll4 endocytosis controlling Notch activation (PMID:34820962). EHD2 additionally acts as a mechanotransducer: under mechanical stress it is released from caveolae, SUMOylated, and translocated to the nucleus, where it represses transcription of target genes including caveolae constituents and CDKN1A/p21 via a KLF7-dependent mechanism (PMID:22448906, PMID:30348749). Independent of caveolae, EHD2 couples endocytic recycling to the actin cytoskeleton and membrane-fusion/repair machinery through its EH-domain partner EHBP1 and the ferlins myoferlin and Fer1L5, contributing to myoblast fusion and sarcolemmal repair (PMID:14676205, PMID:18502764, PMID:22679923), and forms a Rab10–EHBP1–EHD2 complex driving lipophagy of lipid droplets (PMID:28028537).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 2003 Medium

    Established EHD2's earliest known function—linking endocytosis to the actin cytoskeleton—by identifying its EH-domain partner and a defined trafficking defect.

    Evidence siRNA knockdown, co-IP with EHBP1, and transferrin/GLUT4 endocytosis assays

    PMID:14676205

    Open questions at the time
    • Did not address caveolar localization or ATPase mechanism
    • EHBP1-actin coupling not structurally resolved
  2. 2004 Medium

    Connected EHD2 to insulin-regulated GLUT4 trafficking, implying a role in metabolic membrane transport.

    Evidence MS identification in GLUT4 vesicles, Co-IP, GST pull-down, antibody inhibition in permeabilized adipocytes

    PMID:15182197

    Open questions at the time
    • Mechanistic link to caveolae not yet known
    • Adaptor interactions not validated in vivo
  3. 2008 Medium

    Linked EHD2-driven endocytic recycling to the membrane-fusion machinery of myoblasts via direct ferlin binding.

    Evidence C2-domain binding mapping to myoferlin, dominant-negative EHD2, fusion and recycling assays

    PMID:18502764

    Open questions at the time
    • Whether caveolae are involved in ferlin trafficking unclear
    • Single lab
  4. 2010 Medium

    Extended the ferlin connection to Fer1L5, showing EHD2 is specifically required for ferlin delivery to the plasma membrane.

    Evidence C2-domain binding assay, siRNA knockdown, plasma membrane translocation and fusion assays

    PMID:21177873

    Open questions at the time
    • Molecular basis of selective EHD2 vs EHD1 roles unresolved
  5. 2010 Low

    Reported a palmitoylation-dependent prohibitin–EHD2 plasma membrane interaction.

    Evidence Cys69 palmitoylation mutagenesis, membrane fractionation, PHB-EHD2 Co-IP

    PMID:20555396

    Open questions at the time
    • Single Co-IP with no functional follow-up on EHD2's role
    • No reciprocal validation
  6. 2011 Medium

    Placed EHD2 upstream of Rho-GTPase signaling, showing its trafficking control depends on nucleotide binding and Rac1.

    Evidence Yeast two-hybrid (Nek3, Vav1), Rac1 activity assay, cholera toxin trafficking, P-loop mutagenesis

    PMID:21756249

    Open questions at the time
    • Whether Rac1 regulation acts through caveolae not addressed
    • Direct vs indirect Vav1 link unclear
  7. 2012 High

    Redefined EHD2 as a third structural component of caveolae, establishing the central caveolar stabilization function and its ATPase/oligomerization basis.

    Evidence Live imaging, EM, ATPase assays, sucrose gradients, FRAP, siRNA/dominant-negative, Co-IP with pacsin2 and cavin1

    PMID:22323287 PMID:22505029

    Open questions at the time
    • Atomic-resolution scaffold geometry not yet resolved
    • How ATPase cycle is regulated in cells unclear
  8. 2012 Medium

    Identified a non-caveolar role in sarcolemmal membrane repair requiring EHD2 ATPase activity.

    Evidence Laser wounding of myotubes, GFP-EHD2 imaging, EHD2 vs EHD1 and mutant comparison

    PMID:22679923

    Open questions at the time
    • Repair partners at the wound site not identified
    • Relationship to ferlin function not tested
  9. 2012 Medium

    Revealed an unexpected nuclear function for EHD2, showing SUMOylation-gated shuttling and transcriptional repression of p21/CDKN1A.

    Evidence NLS/NES mutagenesis, SUMOylation Co-IP, yeast two-hybrid, GAL4 transactivation and KLF7-p21 transcription assays, qRT-PCR

    PMID:22448906

    Open questions at the time
    • Trigger for nuclear shuttling not yet linked to caveolae
    • Direct DNA/chromatin engagement undefined
  10. 2013 Medium

    Defined PIP2 as the primary determinant of EHD2 plasma membrane targeting, independent of actin and EH-domain partners.

    Evidence Confocal imaging with PIP2 pharmacology, Arf6 vacuoles, cytochalasin D, partner siRNA, domain deletions

    PMID:24040268

    Open questions at the time
    • Specific PIP2-binding residues not mapped here
    • Single lab
  11. 2014 High

    Provided the structural basis for membrane insertion, showing the N-terminus folds into the GTPase domain and can wedge into the bilayer to create curvature.

    Evidence EPR, X-ray crystallography, cryo-EM, N-terminal mutagenesis

    PMID:24508342

    Open questions at the time
    • In-cell conformational triggering not directly observed
    • Filament geometry at caveolar necks not resolved
  12. 2015 Medium

    Dissected the NPF/KPF loop motifs controlling localization, dimerization, and syndapin2 binding versus nuclear partitioning.

    Evidence Site-directed mutagenesis, Co-IP, confocal localization, nuclear fractionation

    PMID:25875965

    Open questions at the time
    • How motif occupancy is regulated dynamically unknown
  13. 2016 Medium

    Identified a Rab10–EHBP1–EHD2 complex essential for lipophagy, extending EHD2 to autophagic lipid droplet clearance.

    Evidence siRNA, GTPase-defective Rab10, imaging, Co-IP, LC3 and lipid droplet assays

    PMID:28028537

    Open questions at the time
    • EHD2's specific membrane-shaping step in lipophagy undefined
    • Single lab
  14. 2017 High

    Resolved the conformational cycle: autoinhibited in solution, opening and inserting upon ATP binding, oligomerizing, then detaching on hydrolysis to restrict caveolae dynamics.

    Evidence IRRAS, ATPase assays, mutagenesis, caveolae dynamics assays

    PMID:28223496

    Open questions at the time
    • In-cell timing of the cycle not directly measured
    • What regulates hydrolysis-driven release unclear
  15. 2018 High

    Established EHD2 as a mechanotransducer coupling caveolar tension sensing to nuclear gene regulation and showed its loss abolishes caveolae in cancer cells.

    Evidence Live imaging, metal-replica EM, mechanical stress, SUMOylation, transcriptomics, KO and rescue

    PMID:30348749

    Open questions at the time
    • Direct transcriptional targets and DNA engagement incompletely defined
    • Mechanosensing threshold mechanism unknown
  16. 2018 Medium

    Demonstrated EHD2 stabilizes caveolae to sustain cardiac KATP channel surface expression, with protective relevance to ischemia.

    Evidence Surface biotinylation, patch clamp, dominant-negative EHD2, ischemia assay, EHD paralog comparison

    PMID:29133341

    Open questions at the time
    • In vivo cardiac KO phenotype not tested here
    • Direct KATP–caveolae binding interface undefined
  17. 2019 High

    Linked EHD2-controlled caveolae stability to metabolic fatty acid uptake and obesity via a CD36-dependent pathway, using a whole-animal knockout.

    Evidence EHD2 KO mice, fatty acid uptake, EM caveolae counting, caveolar mobility, CD36/dynamin pharmacology

    PMID:32170013

    Open questions at the time
    • Whether nuclear EHD2 contributes to the metabolic phenotype unclear
  18. 2019 High

    Showed EHD2-dependent caveolar stability governs eNOS surface localization and endothelial NO/Ca2+ signaling.

    Evidence EHD2 KO mice, vascular relaxation, NO measurement, super-resolution eNOS imaging, Ca2+ imaging, HUVEC siRNA

    PMID:31600286

    Open questions at the time
    • Direct eNOS–caveolae retention mechanism not biochemically dissected
  19. 2019 Medium

    Connected EHD2 to adipocyte differentiation and insulin sensitivity, including suppression of PPARγ activity.

    Evidence siRNA, overexpression, imaging, insulin sensitivity, lipolysis, PPARγ activity assays

    PMID:30811273

    Open questions at the time
    • Mechanism linking caveolar EHD2 to PPARγ transcription undefined
  20. 2021 Medium

    Identified EHD2 as a modulator of Notch signaling through caveolae-dependent Dll4 endocytosis, with an in vivo vascular phenotype.

    Evidence Co-localization, caveolae disruption pharmacology, Dll4 internalization, Notch readouts, zebrafish KO

    PMID:34820962

    Open questions at the time
    • Direct EHD2–Dll4 interaction not demonstrated
    • Single lab
  21. 2022 Medium

    Refined the molecular architecture of caveolae by positioning EHD2 at the caveolar body/neck relative to PACSIN2 and caveolin-1.

    Evidence Super-resolution single-molecule localization microscopy and 3D spatial analysis

    PMID:35834519

    Open questions at the time
    • No functional mutagenesis tied to the spatial map
    • Static snapshot, not dynamic
  22. 2023 Medium

    Showed EHD2 maintains plasma membrane integrity required for insulin receptor signaling and GLUT4 translocation in adipocytes.

    Evidence EHD2 KO mice on high-fat diet, 3T3-L1 adipocytes, GLUT4 translocation, insulin signaling, membrane composition, SNARE Co-IP

    PMID:37703099

    Open questions at the time
    • Causal chain from caveolae loss to insulin receptor downregulation incompletely defined
  23. 2023 Medium

    Defined an EHD2–SOCE oncogenic axis whereby caveolar stabilization sustains Orai1 surface expression to drive tumorigenesis.

    Evidence shRNA, CRISPR KO with mouse Ehd2 rescue, surface expression, SOCE, caveolae imaging, tumor/metastasis assays

    PMID:36625722

    Open questions at the time
    • Direct Orai1–caveolae interaction not mapped
    • Single lab
  24. 2025 High

    Provided a near-atomic structural model of EHD2 filaments shaping a highly curved membrane scaffold, with the N-terminus acting as an inter-filament spacer and a KO correlate at caveolar necks.

    Evidence Cryo-electron tomography of reconstituted EHD2-tubulated liposomes plus EM of EHD2 KO endothelial caveolar necks (preprint)

    PMID:bio_10.1101_2025.06.05.658037

    Open questions at the time
    • Preprint, not peer-reviewed
    • In-cell filament organization around native caveolar necks not directly resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How EHD2 nuclear translocation and its transcriptional targets are mechanistically coupled to specific physiological mechanical stimuli, and whether nuclear EHD2 contributes to its metabolic and oncogenic phenotypes, remains unresolved.
  • Direct DNA/chromatin engagement by nuclear EHD2 undefined
  • Full target gene set across tissues unknown
  • Relative contribution of caveolar vs nuclear EHD2 to disease phenotypes unquantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 3 GO:0140657 ATP-dependent activity 3 GO:0005198 structural molecule activity 2 GO:0008092 cytoskeletal protein binding 2 GO:0016787 hydrolase activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005634 nucleus 2 GO:0005811 lipid droplet 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1430728 Metabolism 2 R-HSA-162582 Signal Transduction 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-8953897 Cellular responses to stimuli 1 R-HSA-9612973 Autophagy 1
Partners
CAV1CAVIN1EHBP1FER1L5GLUT4MYOFPACSIN2RAB10
Complex memberships
Rab10-EHBP1-EHD2 complexcaveolae

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 EHD2 localizes to cortical actin filaments at the plasma membrane and couples clathrin-mediated endocytosis to the actin cytoskeleton. Its C-terminal EH domain interacts with NPF repeats in the novel binding partner EHBP1, which contains a calponin homology actin-binding domain. siRNA-mediated silencing of EHD2 or EHBP1 inhibits transferrin and GLUT4 endocytosis into EEA1-positive endosomes. High expression of EHD2 or EHBP1 causes extensive actin reorganization. siRNA knockdown, co-immunoprecipitation, subcellular localization by fluorescence microscopy, endocytosis assays (transferrin, GLUT4) The Journal of biological chemistry Medium 14676205
2004 EHD2 is present in purified GLUT4 vesicles of rat adipocytes and physically co-immunoprecipitates with GLUT4. Insulin selectively enhances EHD2-GLUT4 interaction in an endosomal fraction containing GLUT4 exocytic vesicles. EHD2 also interacts with clathrin adaptor subunits µ1, µ2, and rCALM in GST pull-down experiments. An anti-EHD2 antibody and an EHD2-derived peptide suppressed insulin-induced plasma membrane GLUT4 recruitment in permeabilized adipocytes, indicating EHD2 plays a key role in insulin-induced GLUT4 trafficking. MALDI-TOF MS identification, co-immunoprecipitation, GST pull-down, subcellular fractionation, antibody inhibition assay in SLO-permeabilized adipocytes Biochemistry Medium 15182197
2008 EHD2 directly binds the second C2 domain of myoferlin. Myoferlin-null myoblasts show reduced EHD2 levels, accumulate labeled transferrin, and have delayed recycling. Introduction of dominant-negative EHD2 into myoblasts leads to sequestration of myoferlin and inhibition of myoblast fusion, identifying a molecular link between endocytic recycling and myoblast membrane fusion machinery. Direct binding assay (C2 domain mapping), dominant-negative EHD2 expression, transferrin recycling assay, myoblast fusion assay, immunofluorescence The Journal of biological chemistry Medium 18502764
2010 EHD2 (and EHD1) directly binds Fer1L5 via the second C2 domain of Fer1L5. Reduction of EHD1 and/or EHD2 by siRNA inhibits myoblast fusion, and EHD2 is specifically required for normal translocation of Fer1L5 to the plasma membrane. Direct binding assay (C2 domain mapping), siRNA knockdown, plasma membrane translocation assay, myoblast fusion assay The Journal of biological chemistry Medium 21177873
2011 EHD2 regulates trafficking from the plasma membrane by controlling Rac1 activity. Using yeast two-hybrid, EHD2 was found to interact with Nek3 kinase and associate with Vav1 (a Nek3-regulated GEF for Rho GTPases). Overexpression of wild-type EHD2, but not P-loop (nucleotide-binding) mutants, reduced Rac1 activity. The inhibitory effect of EHD2 on cholera toxin trafficking was partially rescued by co-expression of Rac1. Yeast two-hybrid, co-immunoprecipitation, Rac1 activity assay, cholera toxin trafficking assay, P-loop mutagenesis The Biochemical journal Medium 21756249
2012 EHD2 is specifically and stably associated with caveolae at the plasma membrane. EHD2 dimers oligomerize into rings on highly curved membranes, stimulating intrinsic ATPase activity. EHD2 interacts with pacsin2 and cavin1; ordered membrane assembly requires cavin1 and caveolar integrity. A loop in the nucleotide-binding domain, together with ATP binding, is required for caveolar localization. High EHD2 levels distort/reduce caveolae; depletion results in endocytic, more dynamic and short-lived caveolae. EHD2 constitutes a third structural component of caveolae controlling stability and turnover. Live-cell imaging, electron microscopy, ATPase assay, siRNA depletion, overexpression, co-immunoprecipitation (pacsin2, cavin1), domain mutagenesis Molecular biology of the cell High 22323287
2012 EHD2 associates with the static population of plasma membrane caveolae via ATP binding, interaction with anionic lipids, and oligomerization into large complexes (~60–75S) via EH domain interactions with intrinsic NPF/KPF motifs. ATP hydrolysis is essential for EHD2 binding to caveolae. EHD2 undergoes dynamic exchange at caveolae dependent on a functional ATPase cycle. Depletion of EHD2 by siRNA or dominant-negative expression dramatically increases the fraction of mobile caveolar vesicles from the PM; overexpression confines cholera toxin B to caveolae. The confining role relies on EHD2's capacity to link caveolae to actin filaments. Live-cell imaging (TIRF, FRAP), siRNA knockdown, dominant-negative expression, ATPase mutant analysis, sucrose gradient ultracentrifugation, cholera toxin tracking assay The EMBO journal High 22505029
2012 EHD2 can shuttle to the nucleus in a NLS-dependent manner; nuclear exit depends partially on a NES. SUMOylation of EHD2 was confirmed by co-immunoprecipitation and yeast two-hybrid, and elimination of the SUMOylation site causes major nuclear accumulation. Nuclear EHD2 represses transcription, including repression of the p21WAF1/Cip1 (CDKN1A) gene via a KLF7-dependent transcription assay, confirmed by qRT-PCR in EHD2 overexpression and knockdown cells. Nuclear export inhibition, NLS/NES mutagenesis, co-immunoprecipitation (SUMOylation), yeast two-hybrid, GAL4-based transactivation assay, KLF7-p21 transcription assay, qRT-PCR The Biochemical journal Medium 22448906
2012 EHD2 participates in sarcolemmal membrane repair. Following laser wounding of human myotubes, EHD2 (but not EHD1) accumulates at the injury site and at the repair dome structure. A mutant EHD2 does not accumulate, indicating the ATPase function is required for this role. Live fluorescence imaging of GFP-tagged and endogenous EHD2 after laser wounding, comparison of EHD2 vs EHD1 and mutant EHD2 Traffic (Copenhagen, Denmark) Medium 22679923
2013 Plasma membrane phospholipid PIP2 plays a crucial role in regulating EHD2 subcellular localization. Pharmacological perturbation of PIP2 metabolism causes EHD2 to redistribute away from the plasma membrane. EHD2 localizes to PIP2-enriched vacuoles generated by active Arf6. Cytochalasin D-induced actin collapse does not displace EHD2 from the PM, but both PIP2 and EHD2 co-redistribute to actin aggregates, supporting PIP2 as the primary determinant. EHD2 plasma membrane targeting is independent of syndapin2, EHBP1, or its EH domain. Confocal microscopy, pharmacological PIP2 perturbation, Arf6 overexpression (PIP2-enriched vacuoles), cytochalasin D treatment, siRNA depletion of partner proteins, domain deletion mutants PloS one Medium 24040268
2014 Using EPR spectroscopy and X-ray crystallography, the N-terminus of EHD2 is folded into a hydrophobic pocket of the GTPase domain in solution and can be released into the membrane. Residues at the tip of the helical domain can insert into the membrane and may create membrane curvature by a wedging mechanism. Cryo-EM showed the N-terminus is not essential for oligomerization but regulates targeting and stable association of EHD2 with caveolae. Electron paramagnetic resonance (EPR) spectroscopy, X-ray crystallography, cryo-electron microscopy, mutagenesis of N-terminal region Structure (London, England : 1993) High 24508342
2015 The EHD2 unstructured loop contains two PF motifs (NPF and KPF). The NPF phenylalanine residue is crucial for EHD2 plasma membrane localization, whereas the NPF proline residue is essential for EHD2 dimerization and binding to Syndapin2. The KPF motif NPF-to-APA mutation increases nuclear localization and reduces plasma membrane association. These results support a model in which the N-terminal region regulates availability of the unstructured loop for oligomerization. Site-directed mutagenesis, co-immunoprecipitation (dimerization, Syndapin2 binding), confocal microscopy (localization), nuclear fractionation PloS one Medium 25875965
2016 Rab10, EHBP1, and EHD2 form a novel complex essential for lipophagy in hepatocytes. During autophagy, Rab10 activity is amplified and recruits EHBP1 and EHD2 to nascent autophagic membranes at the lipid droplet surface. Disruption of Rab10 by siRNA or GTPase-defective variant causes lipid droplet accumulation. Rab10 activation is essential for LC3 recruitment to the autophagosome and stimulates association with EHBP1 and EHD2, driving engulfment of lipid droplets. siRNA knockdown, GTPase-defective mutant expression, fluorescence imaging, co-immunoprecipitation, autophagy assays (LC3 recruitment, lipid droplet accumulation) Science advances Medium 28028537
2017 EHD2 is kept in an autoinhibited conformation in solution by its N-terminal residues and EH domain. Upon membrane binding, EHD2 adopts an open conformation by tilting its helical domains (demonstrated by infrared reflection-absorption spectroscopy). ATP binding enables partial insertion of EHD2 into the membrane, where G-domain-mediated oligomerization occurs. ATP hydrolysis is coupled to detachment of EHD2 from the membrane. Regulation of EHD2 oligomerization in the membrane-bound state is required for restricting caveolae dynamics. Infrared reflection-absorption spectroscopy (IRRAS), ATPase assays, mutagenesis, cell-based caveolae dynamics assays Proceedings of the National Academy of Sciences of the United States of America High 28223496
2018 Under mechanical stress, EHD2 is rapidly released from caveolae, SUMOylated, and translocated to the nucleus where it regulates transcription of several genes including those coding for caveolae constituents. EHD2 is required to maintain the caveolae reservoir at the plasma membrane during membrane tension variations. Breast cancer cells lacking EHD2 show a complete absence of caveolae and lack gene regulation under mechanical stress; re-expression of EHD2 restores both functions. Live-cell imaging, metal-replica electron microscopy, mechanical stress assays, SUMOylation detection, nuclear fractionation, transcriptome analysis (gene expression), EHD2 KO and rescue The Journal of cell biology High 30348749
2018 EHD2 positively regulates the surface expression of cardiac sarcolemmal KATP channels by stabilizing KATP channel-containing caveolar structures, reducing the rate of endocytosis. EHD2 is specific to KATP channels among EHD family members (EHD1, EHD3, EHD4 had no effect) and does not alter channel unitary conductance or ATP sensitivity. A dominant-negative EHD2 mutant sensitizes cardiomyocytes to ischemic damage. Surface biotinylation, immunofluorescence, patch clamping, dominant-negative EHD2 expression, cardiomyocyte ischemia assay, comparison across EHD paralogs FASEB journal Medium 29133341
2019 EHD2 controls a caveolae- and CD36-dependent fatty acid uptake pathway in adipocytes. Global genetic ablation of EHD2 in mice leads to increased lipid droplet size in fat tissue and elevated fatty acid uptake. EHD2-null adipose tissue shows increased numbers of detached caveolae. EHD2 expression is down-regulated in visceral fat of obese mouse models and obese patients. EHD2 knockout mice, fatty acid uptake assay, electron microscopy (caveolae counting), live-cell caveolar mobility assay, CD36/dynamin inhibitor pharmacology Proceedings of the National Academy of Sciences of the United States of America High 32170013
2019 EHD2-controlled caveolar dynamics orchestrates eNOS/NO activity. Loss of EHD2 in small arteries increases detached caveolae numbers, impairs mesenteric artery relaxation, and decreases nitric oxide production without changing eNOS expression levels. Super-resolution imaging shows eNOS redistributes from the plasma membrane to internalized detached caveolae in EHD2-lacking tissues/cells. EHD2 deletion or knockdown also reduces cytosolic Ca2+ peaks following ATP stimulus in HUVECs. EHD2 knockout mice, vascular relaxation assay, NO measurement, super-resolution microscopy (eNOS localization), Ca2+ imaging, siRNA knockdown in HUVECs PloS one High 31600286
2019 EHD2 protein expression is up-regulated at the onset of triglyceride accumulation during adipocyte differentiation. EHD2 localizes to caveolae adjacent to cell surface-associated lipid droplets in primary human adipocytes. siRNA silencing of EHD2 impairs differentiation, insulin sensitivity, lipid storage, and lipolysis. EHD2 overexpression increases lipolytic signaling and suppresses PPARγ transcription factor activity. siRNA knockdown, EHD2 overexpression, fluorescence imaging, insulin sensitivity assay, lipolysis assay, PPARγ activity assay Molecular biology of the cell Medium 30811273
2021 EHD2 is a novel modulator of Notch activation in endothelial cells through controlling endocytosis of Dll4. EHD2 co-localizes with plasma membrane Dll4 and caveolae. Chemical disruption of caveolae prevents EHD2 organization around Dll4 and blocks Dll4 internalization, blunting Notch activation. EHD2 knockout in zebrafish increases dysmorphic intersomitic vessel sprouts and reduces downstream Notch signaling. In vitro co-localization (immunofluorescence), caveolae disruption pharmacology, Dll4 internalization assay, Notch signaling readouts, zebrafish EHD2 knockout Microcirculation (New York, N.Y. : 1994) Medium 34820962
2022 Super-resolution single-molecule localization microscopy revealed that PACSIN2 and EHD2 both co-localize with caveolin-1 at caveolae. The mean centroid of the PACSIN2 F-BAR domain is positioned closer to the plasma membrane than EHD2 and caveolin-1 centroids, suggesting PACSIN2 connects caveolae to the plasma membrane while EHD2 is positioned at the caveolar body/neck. Super-resolution single-molecule localization microscopy (SMLM), 3D spatial analysis of PACSIN2, EHD2, and caveolin-1 relative positions PloS one Medium 35834519
2023 EHD2 deficiency in adipocytes is associated with deterioration of insulin signal transduction and impaired insulin-stimulated GLUT4 translocation. EHD2 loss is linked to altered plasma membrane lipid and protein composition, reduced insulin receptor expression, and diminished insulin-dependent SNARE protein complex formation, indicating EHD2 is required for plasma membrane integrity and downstream insulin receptor signaling. EHD2 knockout mice (high-fat diet), 3T3-L1 adipocytes, GLUT4 translocation assay, insulin signaling assays, membrane lipid/protein composition analysis, SNARE complex co-immunoprecipitation Molecular biology of the cell Medium 37703099
2023 EHD2 stabilizes plasma membrane caveolae to ensure high cell surface expression of the SOCE-linked calcium channel Orai1. EHD2 shRNA knockdown and CRISPR-Cas9 knockout with mouse Ehd2 rescue in TNBC cell lines demonstrates that EHD2 promotes tumorigenesis and metastasis through store-operated calcium entry (SOCE), defining an EHD2-SOCE oncogenic axis. shRNA knockdown, CRISPR-Cas9 knockout, Ehd2 rescue, surface expression assays, SOCE assay, caveolae imaging, tumorigenesis and metastasis assays eLife Medium 36625722
2025 Cryo-electron tomography of EHD2 oligomerized on tubulated liposomes revealed that EHD2 forms filaments creating a highly curved membrane scaffold that stabilizes a tubular membrane geometry with undulations along the tube axis. The amino-terminal sequence facilitates this geometry by inserting into the membrane, acting as a spacer between adjacent filaments. In endothelial cells lacking EHD2, caveolar necks become narrower and elongated, providing a cellular correlate to the structural model. Cryo-electron tomography, in vitro tubulated liposome reconstitution with EHD2 oligomers, endothelial cells from EHD2 knockout with electron microscopy of caveolar neck morphology bioRxivpreprint High bio_10.1101_2025.06.05.658037
2010 Palmitoylation of prohibitin (PHB) at Cys69 is required for PHB membrane translocation, which in turn facilitates PHB tyrosine phosphorylation and its interaction with EHD2. Thus, the EHD2-PHB interaction at the plasma membrane is dependent on PHB palmitoylation-driven membrane recruitment. Palmitoylation site mutagenesis (Cys69), membrane fractionation, co-immunoprecipitation (PHB-EHD2), phosphorylation detection Biochemistry and cell biology Low 20555396

Source papers

Stage 0 corpus · 49 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Ehd2, a rice ortholog of the maize INDETERMINATE1 gene, promotes flowering by up-regulating Ehd1. Plant physiology 200 18790997
2012 EHD2 regulates caveolar dynamics via ATP-driven targeting and oligomerization. Molecular biology of the cell 157 22323287
2016 A novel Rab10-EHBP1-EHD2 complex essential for the autophagic engulfment of lipid droplets. Science advances 154 28028537
2012 Oligomers of the ATPase EHD2 confine caveolae to the plasma membrane through association with actin. The EMBO journal 136 22505029
2003 EHD2 and the novel EH domain binding protein EHBP1 couple endocytosis to the actin cytoskeleton. The Journal of biological chemistry 135 14676205
2008 The endocytic recycling protein EHD2 interacts with myoferlin to regulate myoblast fusion. The Journal of biological chemistry 93 18502764
2000 EHD2, EHD3, and EHD4 encode novel members of a highly conserved family of EH domain-containing proteins. Genomics 80 10673336
2009 EHD2 inhibits ligand-induced endocytosis and signaling of the leucine-rich repeat receptor-like protein LeEix2. The Plant journal : for cell and molecular biology 73 19392695
2018 EHD2 is a mechanotransducer connecting caveolae dynamics with gene transcription. The Journal of cell biology 62 30348749
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
2020 EHD2-mediated restriction of caveolar dynamics regulates cellular fatty acid uptake. Proceedings of the National Academy of Sciences of the United States of America 50 32170013
2017 EHD2 restrains dynamics of caveolae by an ATP-dependent, membrane-bound, open conformation. Proceedings of the National Academy of Sciences of the United States of America 44 28223496
2014 Structural insights into membrane interaction and caveolar targeting of dynamin-like EHD2. Structure (London, England : 1993) 43 24508342
2012 Sarcolemmal repair is a slow process and includes EHD2. Traffic (Copenhagen, Denmark) 43 22679923
2009 The coiled-coil domain of EHD2 mediates inhibition of LeEix2 endocytosis and signaling. PloS one 31 19936242
2004 EHD2 interacts with the insulin-responsive glucose transporter (GLUT4) in rat adipocytes and may participate in insulin-induced GLUT4 recruitment. Biochemistry 31 15182197
2016 Phosphatidylinositol glycan anchor biosynthesis, class X containing complex promotes cancer cell proliferation through suppression of EHD2 and ZIC1, putative tumor suppressors. International journal of oncology 27 27572108
2013 Effects of EHD2 interference on migration of esophageal squamous cell carcinoma. Medical oncology (Northwood, London, England) 27 23354948
2011 EHD2 mediates trafficking from the plasma membrane by modulating Rac1 activity. The Biochemical journal 27 21756249
2013 Role of phosphatidylinositol 4,5-bisphosphate in regulating EHD2 plasma membrane localization. PloS one 26 24040268
2010 Palmitoylation of prohibitin at cysteine 69 facilitates its membrane translocation and interaction with Eps 15 homology domain protein 2 (EHD2). Biochemistry and cell biology = Biochimie et biologie cellulaire 26 20555396
2012 EHD2 shuttles to the nucleus and represses transcription. The Biochemical journal 25 22448906
2015 Role of EHD2 in migration and invasion of human breast cancer cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 23 25557791
2019 EHD2 regulates adipocyte function and is enriched at cell surface-associated lipid droplets in primary human adipocytes. Molecular biology of the cell 21 30811273
2018 The trafficking protein, EHD2, positively regulates cardiac sarcolemmal KATP channel surface expression: role in cardioprotection. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 21 29133341
2023 Exogenous abscisic acid represses rice flowering via SAPK8-ABF1-Ehd1/Ehd2 pathway. Journal of advanced research 20 37399924
2019 eNOS-NO-induced small blood vessel relaxation requires EHD2-dependent caveolae stabilization. PloS one 16 31600286
2014 Upregulation of EHD2 after intracerebral hemorrhage in adult rats. Journal of molecular neuroscience : MN 15 24664435
2013 A point mutation in the zinc finger motif of RID1/EHD2/OsID1 protein leads to outstanding yield-related traits in japonica rice variety Wuyunjing 7. Rice (New York, N.Y.) 14 24280027
2013 Scratching the surface: actin' and other roles for the C-terminal Eps15 homology domain protein, EHD2. Histology and histopathology 14 24347515
2023 EHD2 overexpression promotes tumorigenesis and metastasis in triple-negative breast cancer by regulating store-operated calcium entry. eLife 11 36625722
2020 TUSC8 inhibits the development of osteosarcoma by sponging miR‑197‑3p and targeting EHD2. International journal of molecular medicine 11 32945345
2009 EHD2 inhibits signaling of leucine rich repeat receptor-like proteins. Plant signaling & behavior 10 19820301
2021 EHD2 Overexpression Suppresses the Proliferation, Migration, and Invasion in Human Colon Cancer. Cancer investigation 7 33356637
2021 Ese-3 contributes to colon cancer progression by downregulating EHD2 and transactivating INPP4B. American journal of cancer research 7 33520362
2015 Role of the EHD2 unstructured loop in dimerization, protein binding and subcellular localization. PloS one 7 25875965
2013 The function of EHD2 in endocytosis and defense signaling is affected by SUMO. Plant molecular biology 7 24154852
2022 Differential requirements for the Eps15 homology domain proteins EHD4 and EHD2 in the regulation of mammalian ciliogenesis. Traffic (Copenhagen, Denmark) 6 35510564
2022 Super-resolution analysis of PACSIN2 and EHD2 at caveolae. PloS one 6 35834519
2021 EHD2 modulates Dll4 endocytosis during blood vessel development. Microcirculation (New York, N.Y. : 1994) 6 34820962
2022 qHD5 encodes an AP2 factor that suppresses rice heading by down-regulating Ehd2 expression. Plant science : an international journal of experimental plant biology 4 36041562
2020 EHD2 is a Predictive Biomarker of Chemotherapy Efficacy in Triple Negative Breast Carcinoma. Scientific reports 4 32409676
2024 OsCOL5 suppresses heading through modulation of Ghd7 and Ehd2, enhancing rice yield. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 3 38884792
2023 EHD2 regulates plasma membrane integrity and downstream insulin receptor signaling events. Molecular biology of the cell 3 37703099
2023 Novel MYCBP::EHD2 and RUNX1::ZNF780A Fusion Genes in T-cell Acute Lymphoblastic Leukemia. Cancer genomics & proteomics 2 36581344
2024 EH domain-containing protein 2 (EHD2): Overview, biological function, and therapeutic potential. Cell biochemistry and function 1 38613224
2025 A Series of Novel Alleles of Ehd2 Modulating Heading and Salt Tolerance in Rice. Plants (Basel, Switzerland) 0 39861650
2023 EHD2, a novel HIF target gene, is a promising biomarker in clear cell renal cell carcinoma. International journal of clinical and experimental pathology 0 38059172
2020 [Unsaturated fatty acid of Actinidia chinesis planch seed oil (kiwi fruit essence) inhibits growth and metastasis of transplanted tumor in lung adenocarcinoma mice by up-regulating EHD2 expression]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 32727647

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