Affinage

ENAH

Protein enabled homolog · UniProt Q8N8S7

Length
591 aa
Mass
66.5 kDa
Annotated
2026-06-09
100 papers in source corpus 39 papers cited in narrative 39 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

ENAH (Mena) is an actin-regulatory scaffold of the Ena/VASP family that couples membrane receptors and adhesion structures to actin filament assembly, promoting filopodia, lamellipodia, focal-adhesion dynamics, and cell motility (PMID:8861907, PMID:10069337). Its modular architecture underlies this scaffolding role: the EVH1 domain recognizes proline-rich SLiMs (FPPPP/PPLP-type motifs) in partners including the FE65 WW domain, Xin, the IRSp53 SH3 domain, and Tes LIM3, with a diverged EVH1 pocket and noncanonical secondary site conferring paralog-specific, often bivalent recognition of extended ligands (PMID:8861907, PMID:9407065, PMID:11696321, PMID:16631741, PMID:18158903, PMID:35076015); a central proline-rich region binds the G-actin-binding profilin I/IIa, and profilin is required for Mena/VASP function at the leading edge where it sets the balance between filopodia and Arp2/3-driven lamellipodia (PMID:8861907, PMID:10069337, PMID:32470361). Mena is targeted to distinct sites by dedicated partners—zyxin recruits it to focal adhesions, Myosin X transports it to filopodial tips, and it engages α5β1 integrin via LERER repeats to drive outside-in signaling, FAK/paxillin phosphorylation, and fibronectin fibrillogenesis (PMID:15158464, PMID:16505170, PMID:22908313). Mena and VASP are functionally redundant in actin-dependent neural development, and combined loss causes neurulation, craniofacial, and CNS/PNS axon-tract defects (PMID:15371503); in heart, Mena localizes to intercalated discs and Z-discs and is required for connexin-43 organization and normal cardiac conduction (PMID:23937664, PMID:21335464). Beyond direct cytoskeletal roles, Mena nucleates regulatory complexes—it constitutively binds PTP1B and SHIP2 to provide negative feedback on EGFR signaling, links Cdc42–IRSp53 to filopodium initiation, anchors gephyrin–profilin at inhibitory synapses, and forms an HnrnpK/PCBP1 ribonucleoprotein that controls BDNF-stimulated local translation of dyrk1a in axons (PMID:11696321, PMID:12967995, PMID:26337385, PMID:27597754, PMID:28735747). Alternative splicing diversifies its output: the MenaINV isoform sensitizes carcinoma cells to EGF by impairing PTP1B recruitment to EGFR and to invadopodia, promoting invadopodium maturation, intravasation, and metastasis, whereas Mena11a suppresses actin polymerization and protrusion; isoform choice is governed by ESRP1, PTBP1, and RBFOX2 downstream of EGF, Notch1, TGF-β/hypoxia, and matrix-stiffness/FAK signaling (PMID:19081071, PMID:21670198, PMID:26337385, PMID:27824079, PMID:27901093, PMID:27748415, PMID:31075540, PMID:33089214, PMID:37027295). MENA is itself a transcriptional target of Wnt/β-catenin–TCF4 and Notch1, and is phosphorylated by c-Abl at Tyr-296 in an Abi-1-facilitated manner (PMID:12672821, PMID:22615875, PMID:27901093).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1996 High

    Established that Mena is an actin-assembly protein, defining its EVH1 domain as a proline-rich-motif reader and linking it to profilin and microfilament formation.

    Evidence Affinity chromatography, immunofluorescence localization, and overexpression in fibroblasts producing F-actin-rich outgrowths

    PMID:8861907

    Open questions at the time
    • Did not define the EVH2/actin-binding contribution biochemically
    • No in vivo loss-of-function at this stage
  2. 1997 High

    Identified the FE65 WW domain as a direct PPLP-motif partner of Mena, extending the proline-rich interactome beyond actin machinery.

    Evidence Affinity purification from brain, SPOTS peptide competition, co-IP from COS cells

    PMID:9407065

    Open questions at the time
    • Functional consequence of the Mena–FE65 complex not established
    • No structural detail of the interaction
  3. 1999 High

    Placed Mena in the profilin actin pathway genetically and localized it to growth-cone filopodial tips, connecting molecular binding to neural development.

    Evidence Direct binding assay plus Mena-/- x Profilin I+/- double-mutant mouse genetics and neuronal immunofluorescence

    PMID:10069337

    Open questions at the time
    • Whether Mena acts strictly upstream of or parallel to profilin unresolved
    • Mechanism of filopodial tip targeting not defined here
  4. 2003 High

    Defined how Mena is post-translationally and combinatorially regulated, identifying Abi-1-facilitated c-Abl phosphorylation at Tyr-296 and gephyrin competition for the profilin site at synapses.

    Evidence Yeast two-hybrid, co-IP, site-directed mutagenesis (Abi-1/Abl); co-precipitation and competition assays from brain (gephyrin)

    PMID:12672821 PMID:12967995

    Open questions at the time
    • Functional output of Tyr-296 phosphorylation on actin assembly not measured
    • Gephyrin interaction lacks reciprocal structural validation
  5. 2004 High

    Resolved how Mena reaches its sites of action and demonstrated Mena/VASP redundancy in development, plus paralog-selective EVH1 ligand engagement.

    Evidence Co-IP and live co-movement imaging (Myosin X transport); Mena/VASP double-KO mouse phenotyping; designed miniature-protein binding and Xenopus motility assay

    PMID:14709031 PMID:15158464 PMID:15371503

    Open questions at the time
    • Quantitative contribution of Myosin X transport versus diffusion not resolved
    • Paralog-specific endogenous ligands not yet identified
  6. 2006 High

    Identified site-specific recruitment factors, showing zyxin is required for Mena focal-adhesion targeting and Xin links Mena to cardiac intercalated discs.

    Evidence Zyxin knockout with localization/motility readouts; EVH1 direct binding and cardiomyocyte co-localization (Xin)

    PMID:16505170 PMID:16631741

    Open questions at the time
    • Whether zyxin recruits Mena directly versus via intermediates not fully separated
    • Functional role of Xin isoform-selective binding unclear
  7. 2007 High

    Provided structural and functional logic for EVH1-mediated regulation and connected Mena to filopodia initiation downstream of Cdc42/IRSp53 with disease relevance.

    Evidence Crystal structure of Tes-LIM3:EVH1 with mutagenesis and migration assays; synaptopodin binding to IRSp53 with FP4-Mito inhibitor in an in vivo proteinuria model

    PMID:17569780 PMID:18158903

    Open questions at the time
    • Endogenous regulation of Mena displacement by Tes in vivo not quantified
    • How IRSp53:Mena synergy nucleates filaments mechanistically unresolved
  8. 2008 High

    Defined alternative splicing as a functional switch, establishing MenaINV as a pro-invasive, pro-metastatic isoform sensitizing cells to EGF.

    Evidence Forced isoform expression with in vitro invasion and in vivo xenograft metastasis assays

    PMID:19081071

    Open questions at the time
    • Molecular basis of EGF sensitization not yet known at this stage
    • Splicing regulators driving the switch unidentified here
  9. 2011 High

    Connected Mena isoforms to paracrine tumor-cell behavior and uncovered required cardiac functions in connexin-43 organization and conduction.

    Evidence Intravital imaging and paracrine co-culture (MenaINV/Mena11a); Mena KO echocardiography/ECG/EM and Mena–Rac1 co-IP with Cx43 readouts

    PMID:21335464 PMID:21670198 PMID:24186093

    Open questions at the time
    • Direct molecular targets coupling Mena to Cx43 trafficking not defined
    • Whether cardiac phenotype is cell-autonomous unresolved
  10. 2012 High

    Established Mena as a direct α5β1 integrin effector for outside-in signaling and identified Wnt/β-catenin–TCF4 as a transcriptional driver of MENA.

    Evidence Direct binding/domain mapping to α5 LERER repeats with fibrillogenesis assays; luciferase reporter, ChIP, and TCF4 overexpression/DN

    PMID:22615875 PMID:22908313 PMID:23129656

    Open questions at the time
    • Structural basis of LERER-repeat recognition not solved
    • Interplay between transcriptional and splicing control not integrated
  11. 2013 High

    Extended Mena function to membrane trafficking and cardiac actin networks, linking it to EGFR clathrin-mediated endocytosis via lamellipodin and to αII-spectrin at Z-/intercalated discs.

    Evidence Co-IP, EGFR endocytosis assays, clathrin-pit live imaging; cardiac double-KO with echocardiography/ECG

    PMID:23937664 PMID:24076656

    Open questions at the time
    • Whether Mena's endocytic role requires its actin activity not fully separated
    • Direct spectrin-binding interface not mapped
  12. 2015 High

    Resolved the molecular mechanism of MenaINV's EGF sensitization through a Mena–PTP1B/SHIP2 negative feedback module on EGFR, and tied Mena to actin-dependent Golgi linking.

    Evidence Co-IPs of Mena–PTP1B/SHIP2/EGFR complexes with phospho-EGFR readouts; in vitro GRASP65 oligomerization and Mena-depletion Golgi morphology assays

    PMID:26337385 PMID:26538023

    Open questions at the time
    • Structural basis of PTP1B/SHIP2 association with Mena not defined
    • Golgi role rests on single-lab reconstitution
  13. 2016 Medium

    Mechanistically dissected isoform-specific behavior—MenaINV blocks PTP1B-dependent cortactin dephosphorylation to mature invadopodia, SHIP2 recruits Mena to invadopodia, Mena11a suppresses protrusion, Notch1 drives MenaINV, and MenaINV confers taxane resistance.

    Evidence Live invadopodium imaging, phospho-cortactin/PTP1B localization, reciprocal SHIP2 co-IP with metastasis model, isoform siRNA/TIRF, Notch1 KD epistasis, microtubule stability/MEK inhibitor rescue

    PMID:27597754 PMID:27748415 PMID:27811011 PMID:27824079 PMID:27901093

    Open questions at the time
    • PTP1B displacement at invadopodia not biochemically reconstituted
    • Phospho-site in exon 11a governing Mena11a function not fully characterized
  14. 2017 High

    Revealed a non-canonical role for Mena as part of an HnrnpK/PCBP1 ribonucleoprotein controlling activity-dependent local mRNA translation in axons.

    Evidence RNA-IP, co-IP with RBPs, polysome assays, BDNF-stimulated reporter translation, RNA-seq of Mena-associated mRNAs

    PMID:28735747

    Open questions at the time
    • Whether RNA regulation requires Mena's actin activity unknown
    • Direct RNA contacts of Mena versus partner RBPs not separated
  15. 2019 Medium

    Identified PTBP1 and a TES-mediated mechanism as regulators of MENA function, controlling exon-11a skipping and Mena–lamellipodin complex formation.

    Evidence RNA pulldown with mutation analysis and KD/rescue invasion assays (PTBP1); IP-MS and co-IP epistasis (TES–Mena–Lpd)

    PMID:30728082 PMID:31075540

    Open questions at the time
    • Combinatorial control with ESRP1/RBFOX2 not integrated
    • TES disruption of Mena–Lpd not structurally defined
  16. 2020 Medium

    Defined profilin 1 as essential for Mena/VASP leading-edge function and showed PFN1 levels set the filopodia/lamellipodia balance.

    Evidence PFN1 CRISPR/siRNA KO, leading-edge IF, actin polymerization and filopodia/lamellipodia live imaging

    PMID:32470361

    Open questions at the time
    • Quantitative thresholds in vivo unknown
    • Single-lab dataset
  17. 2022 High

    Provided a structural and thermodynamic framework for ENAH EVH1 specificity, defining a diverged pocket and a secondary site enabling high-affinity bivalent SLiM engagement (e.g., PCARE).

    Evidence Proteomic peptide screen, structural analysis, ITC, mutagenesis

    PMID:35076015

    Open questions at the time
    • Cellular relevance of newly identified binders not tested
    • Full-length context of bivalent engagement not resolved
  18. 2023 Medium

    Linked mechanical input to MENA biology, showing matrix stiffness raises MENA expression via FAK and lowers ESRP1 to shift splicing toward pro-intravasation isoforms.

    Evidence Tunable hydrogel 3D culture, FAK inhibition, ESRP1 manipulation with isoform assays, in vivo intravasation model, TCGA analysis

    PMID:37027295

    Open questions at the time
    • Direct transcriptional link from FAK to MENA not defined
    • Single-lab mechanistic dissection

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse Mena complexes (integrin, PTP1B/SHIP2, RNP, gephyrin, Golgi) are spatially and temporally coordinated within a single cell, and how phosphorylation and splicing jointly tune these outputs, remains unresolved.
  • No unified model integrating splicing, phosphorylation, and partner choice
  • Structures of most full-length Mena complexes lacking
  • In vivo isoform-specific knock-in phenotypes incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0008092 cytoskeletal protein binding 3 GO:0098772 molecular function regulator activity 2 GO:0003723 RNA binding 1
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3 GO:0005829 cytosol 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-1266738 Developmental Biology 2 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-8953854 Metabolism of RNA 1
Partners
EVLINPPL1ITGA5PFN1PTPN1TESVASPZYXIN
Complex memberships
Cdc42–IRSp53–Mena complexHnrnpK/PCBP1 ribonucleoproteinMena–PTP1B–SHIP2/EGFR complexgephyrin–profilin–Mena/VASP complex

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Mena contains a conserved EVH1 domain that targets it to proteins containing a specific proline-rich motif (FPPPP); Mena associates with the surface of Listeria monocytogenes and with the G-actin binding protein profilin, and expression of neural-enriched Mena isoforms in fibroblasts induces abnormal F-actin-rich outgrowths, establishing a role in actin polymerization and microfilament assembly. Affinity chromatography, subcellular localization by immunofluorescence, overexpression in fibroblasts with morphological readout Cell High 8861907
1999 Mena binds directly to Profilin I; genetic epistasis shows that Mena-deficient mice heterozygous for Profilin I deletion die in utero with neurulation defects, placing Mena functionally upstream of or in the same pathway as Profilin I in actin-dependent processes. Mena is concentrated at the tips of growth cone filopodia in primary neurons and is required for commissure formation. Direct binding assay, genetic double-mutant analysis (Mena-/- x Profilin I+/-), immunofluorescence in primary neurons Neuron High 10069337
1997 The FE65 WW domain binds directly to proline-rich sequences in Mena containing a PPLP core motif; the Mena–FE65 complex forms in vivo as demonstrated by co-immunoprecipitation from COS cell extracts. Affinity purification from mouse brain lysates, SPOTS peptide competition assay, co-immunoprecipitation The Journal of biological chemistry High 9407065
2001 Cdc42 interacts with IRSp53 at a partial CRIB motif, relieving an autoinhibitory intramolecular interaction, which allows the IRSp53 SH3 domain to recruit Mena; the resulting IRSp53:Mena complex acts synergistically to initiate actin filament assembly into filopodia. Affinity chromatography (SH3 domain pulldown to identify Mena), overexpression epistasis, dominant-negative fragment inhibition assay Current biology : CB High 11696321
2003 Mena binds directly to profilin I and profilin IIa and to members of the Mena/VASP family; gephyrin co-precipitates with profilin and Mena/VASP from brain tissue, with interaction requiring the E-domain of gephyrin (not the proline-rich domain), and gephyrin competes with G-actin and phospholipids for the profilin binding site. Co-precipitation from tissue and cell lysates, domain mapping, competition assay The Journal of neuroscience Medium 12967995
2003 Abl interactor 1 (Abi-1) binds to Mena via the EVH1 domain of Mena and the polyproline region of Abi-1, and dramatically promotes c-Abl-mediated tyrosine phosphorylation of Mena specifically at Tyr-296. Yeast two-hybrid, co-immunoprecipitation in mammalian cells, site-directed mutagenesis (Tyr296 mutant) The Journal of biological chemistry High 12672821
2004 Myosin X (M10) binds to Mena/VASP and co-localizes with it at filopodial tips; live-cell imaging shows EGFP-M10 and RFP-VASP moving together from the base to the tip of filopodia, and the amount of VASP at the tip is proportional to M10 levels, demonstrating that Myosin X transports Mena/VASP to filopodial tips. Co-immunoprecipitation, immunocytochemistry, live fluorescence microscopy (co-movement assay) Biochemical and biophysical research communications Medium 15158464
2004 Genetic deletion of both Mena and VASP causes perinatal lethality with defects in neurulation, craniofacial structures, and CNS/PNS fiber tracts, demonstrating functional redundancy between Mena and VASP in actin-dependent developmental processes. Double-knockout mouse genetics with developmental phenotype analysis The Journal of neuroscience High 15371503
2004 The EVH1 domain of Mena (Mena1-112) displays paralog-specific binding: a miniature protein mimicking the ActA PPII helix binds Mena EVH1 with high affinity and discriminates between Mena, VASP, and Evl EVH1 domains; this miniature protein competed with ActA in Xenopus extracts and decreased L. monocytogenes actin-based motility. In vitro binding assay with designed miniature protein, Xenopus egg extract motility assay Journal of the American Chemical Society High 14709031
2006 Zyxin is required for proper localization of Ena/VASP proteins (including Mena) to focal adhesions; zyxin-null fibroblasts show severely reduced Mena/VASP accumulation at focal adhesions and exhibit deficits in actin stress fiber remodeling and enhanced cell motility. Homologous recombination knockout, immunofluorescence localization, cell motility assays The Journal of cell biology High 16505170
2006 Xin (CMYA1) directly binds the EVH1 domain of Mena and VASP, and in adult heart, Xin and Mena/VASP co-localize with filamin c at intercalated discs; different Xin isoforms produced by intraexonic splicing associate differentially with Mena/VASP. Direct binding assay (EVH1 domain), immunofluorescence co-localization in cardiomyocytes Experimental cell research Medium 16631741
2007 The LIM3 domain of Tes binds specifically to the EVH1 domain of Mena (but not VASP or Evl), occludes the canonical FPPPP-binding site, and competes with FPPPP-containing proteins; crystal structure of the LIM3:EVH1 complex reveals the molecular basis of specificity. LIM3 expression displaces Mena from the leading edge and focal adhesions and regulates cell migration through a Mena-dependent mechanism. Crystal structure determination, in vitro binding assay, structure-based gain-of-function mutagenesis, cell-based localization and migration assay Molecular cell High 18158903
2007 Synaptopodin directly binds IRSp53 and blocks the binding of Cdc42 and Mena to IRSp53, thereby suppressing Cdc42:IRSp53:Mena-initiated filopodia formation. A Mena inhibitor (FP4-Mito) suppressed aberrant filopodia in synaptopodin-knockdown podocytes and protected mice against LPS-induced proteinuria. Direct binding assay, siRNA knockdown with filopodia quantification, in vivo LPS-proteinuria model with FP4-Mito inhibitor The American journal of pathology High 17569780
2007 EGF treatment upregulates hMena and its splice variant hMena+11a and specifically increases phosphorylation of the hMena+11a isoform, which in turn leads to increased p42/44 MAPK activation and cell proliferation; hMena knockdown reduces MAPK phosphorylation and EGF-driven proliferative response. Isoform-specific cloning, Western blot phosphorylation analysis, siRNA knockdown with MAPK/proliferation readout Cancer research Medium 17363586
2008 The Mena invasion isoform MenaINV sensitizes carcinoma cells to EGF-induced membrane protrusion and matrix degradation, and increases lung metastasis; MenaINV is more effective than canonical Mena in driving metastases and EGF-dependent invasion in vivo and in vitro. Forced expression, in vitro invasion assay, in vivo mouse xenograft metastasis model, in vivo invasion assay Developmental cell High 19081071
2011 MenaINV promotes coordinated streaming motility, transendothelial migration, and intravasation dependent on a macrophage-tumor cell paracrine loop. Mena11a expression decreases CSF1 expression and ablates paracrine-mediated invasion and intravasation. Intravital multiphoton microscopy, transendothelial migration assay, in vivo intravasation quantification, paracrine co-culture experiments Journal of cell science High 21670198
2012 Mena directly binds the carboxy-terminal portion of the α5 integrin cytoplasmic tail via a 91-residue region containing 13 'LERER' repeats; the Mena–α5β1 complex is required for 'outside-in' α5β1 functions including FAK and paxillin phosphorylation, fibrillar adhesion formation, fibronectin fibrillogenesis, and control of cell migration speed. Direct binding assay (pull-down with defined domain), co-immunoprecipitation, mutagenesis mapping, fibronectin fibrillogenesis assay, fibrillar adhesion immunofluorescence The Journal of cell biology High 22908313
2012 MENA is a transcriptional target of the Wnt/β-catenin pathway; TCF4 binding sites in the MENA promoter are functional as shown by luciferase reporter assays, β-catenin/TCF4 overexpression increases MENA mRNA, and chromatin immunoprecipitation shows direct interaction of β-catenin with the MENA promoter in cell lines and mouse tissues. Luciferase reporter assay, chromatin immunoprecipitation (ChIP), overexpression and dominant-negative TCF4 PloS one High 22615875
2012 hMENA splicing is regulated by ESRP1; forced expression of ESRP1 in invasive mesenchymal breast cancer cells causes re-expression of hMENA(11a), a mesenchymal-to-epithelial transition-like phenotypic switch, and decreased cell invasion. ESRP1 forced expression with isoform-specific RT-PCR, invasion assay, cytoskeletal architecture analysis Proceedings of the National Academy of Sciences of the United States of America Medium 23129656
2013 Lamellipodin (Lpd) forms a complex with the EGFR and with Mena; knockdown of Lpd or Mena impairs clathrin-mediated endocytosis (CME) of the EGFR, while Lpd overexpression increases EGFR uptake in an F-actin-dependent manner. Lpd directly interacts with endophilin and localizes to clathrin-coated pits before vesicle scission. Co-immunoprecipitation, siRNA knockdown with EGFR endocytosis assay, live-cell imaging of clathrin-coated pits The EMBO journal High 24076656
2013 Mena and VASP interact with the αII-Spectrin SH3i splice variant specifically at Z-discs and intercalated discs in cardiomyocytes; Mena/VASP double-deficiency disrupts β-actin networks at these structures and causes dilated cardiomyopathy with conduction abnormalities. Co-immunoprecipitation, immunofluorescence fractionation, double-knockout mouse model with echocardiography and ECG Cell communication and signaling : CCS High 23937664
2015 Mena constitutively associates with the tyrosine phosphatase PTP1B and mediates a negative feedback mechanism on EGFR signaling: upon EGF stimulation, Mena–PTP1B complexes are recruited to the EGFR, causing receptor dephosphorylation. Mena also interacts with SHIP2, which is required for PTP1B recruitment to the EGFR. MenaINV expression impairs PTP1B recruitment to the EGFR, explaining MenaINV-mediated sensitization to EGF. Co-immunoprecipitation (Mena–PTP1B, Mena–SHIP2, EGFR complexes), siRNA knockdown with phospho-EGFR readout, motility assays Molecular biology of the cell High 26337385
2015 Mena interacts with GRASP65 on Golgi membranes; depletion of Mena or disruption of actin polymerization causes Golgi fragmentation. In vitro, Mena and microfilaments enhance GRASP65 oligomerization and Golgi membrane fusion, coupling actin polymerization to Golgi ribbon linking. Biochemical co-purification, in vitro GRASP65 oligomerization assay, Mena depletion with Golgi morphology readout Molecular biology of the cell Medium 26538023
2016 MenaINV is recruited to invadopodium precursors shortly after assembly and promotes phosphorylation of cortactin tyrosine 421; MenaINV reduces localization of the phosphatase PTP1B to the invadopodium, thereby inhibiting cortactin dephosphorylation and promoting invadopodium maturation. Fluorescence live imaging of invadopodium assembly, phospho-cortactin immunofluorescence, PTP1B localization assay by imaging, isoform overexpression Scientific reports Medium 27824079
2016 MenaINV expression alters the ratio of dynamic to stable microtubule populations in paclitaxel-treated cells and increases MAPK/ERK signaling; co-treatment with MEK inhibitor restores paclitaxel sensitivity by driving microtubule stabilization, establishing a mechanism for MENA-mediated taxane resistance. Microtubule stability assay (tubulin fractionation), ERK phosphorylation Western blot, MEK inhibitor co-treatment rescue experiment Molecular cancer therapeutics Medium 27811011
2016 Macrophage contact with tumor cells activates Notch1 signaling, which upregulates MenaINV transcription; Notch1 and MenaINV are both required for macrophage-induced invadopodium formation and tumor cell transendothelial migration; Notch pathway inhibition blocks tumor cell dissemination in vivo. Notch1 siRNA knockdown with invadopodium and transendothelial migration readouts, MENA promoter transcription assay, in vivo tumor dissemination assay with Notch inhibitor Scientific reports Medium 27901093
2016 The Mena11a isoform decreases actin polymerization and growth-factor-stimulated lamellipodia protrusion, slows mesenchymal-like cell motility, and its depletion in epithelial cells perturbs cell:cell junctions. A phosphorylation site within the 11a exon is required for some Mena11a-specific functions. Isoform-specific siRNA, actin polymerization assay, membrane protrusion TIRF imaging, cell motility tracking, phospho-site mutagenesis Scientific reports Medium 27748415
2016 SHIP2 directly interacts with Mena (but not VASP) via specific biochemical interactions and recruits Mena to invadopodia; disruption of the SHIP2–Mena interaction reduces ECM degradation, in vitro invasion, and in vivo metastasis. Co-immunoprecipitation, structure-function analysis, invadopodium degradation assay, in vivo metastasis model The Journal of cell biology High 27597754
2017 Mena forms a ribonucleoprotein complex with RNA-binding proteins HnrnpK and PCBP1 in developing neurons, and this complex regulates local translation of specific mRNAs including dyrk1a in axons; Mena is required for BDNF-stimulated local translation of dyrk1a. RNA immunoprecipitation, co-immunoprecipitation with RBPs, polysome/translation assay, BDNF stimulation with reporter translation assay, RNA-seq of Mena-associated mRNAs Neuron High 28735747
2019 PTBP1 binds to polypyrimidine sequences on introns flanking MENA exon 11a (confirmed by RNA pulldown and mutation analysis) and promotes exon 11a skipping; PTBP1 knockdown inhibits MenaΔ11a production and reduces lung cancer cell migration and invasion, while overexpressed MenaΔ11a rescues PTBP1-driven invasion. RNA pulldown assay, mutational analysis of binding sequences, shRNA knockdown with isoform-specific RT-PCR, invasion and migration assays Biochimica et biophysica acta. Gene regulatory mechanisms Medium 31075540
2020 Mena/VASP-based filament assembly at the leading edge requires profilin 1 (PFN1); in PFN1 knockout cells, Mena/VASP is non-functional at the leading edge and Arp2/3 no longer localizes there; varying PFN1 concentrations dictate the balance between Mena/VASP-driven filopodia and Arp2/3-driven lamellipodia. PFN1 CRISPR/siRNA knockout, leading-edge immunofluorescence, actin polymerization assay, live-cell imaging of filopodia/lamellipodia Current biology : CB Medium 32470361
2020 Hypoxia-driven TGF-β signaling transcriptionally represses ESRP1 via SLUG and RBFOX2, leading to skipping of MENA exon 11a and production of the pro-metastatic hMENAΔ11a isoform; exosomal TGF-β contributes to this signaling under hypoxia. TGF-β pathway manipulation, ESRP1 knockdown/overexpression with isoform-specific RT-PCR, ChIP for SLUG at ESRP1 promoter, exosome co-culture experiments NAR cancer Medium 33089214
2022 A proteomic screen of 36-residue proteome-derived peptides against the ENAH EVH1 domain revealed that a diverged pocket on ENAH EVH1 (relative to other Ena/VASP paralogs) recognizes extended SLiMs with flanking prolines; many high-affinity binders use a noncanonical secondary site on EVH1 when harboring two proline-rich motifs; PCARE uses a 23-residue region to achieve the highest known affinity for ENAH EVH1. These interactions display thermodynamic signatures consistent with bivalent engagement. Proteomic peptide screen, structural analysis of EVH1 domain interactions, isothermal titration calorimetry, mutagenesis eLife High 35076015
2023 Matrix stiffness increases MENA expression via focal adhesion kinase (FAK) activity and promotes intravasation; stiffness also decreases ESRP1 expression, triggering alternative splicing of MENA to reduce MENA11a, which further enhances contractility and intravasation. Tunable hydrogel 3D culture, FAK inhibition, ESRP1 knockdown/overexpression with isoform-specific assays, mouse mammary intravasation model, TCGA expression analysis Cell reports Medium 37027295
2011 Mena associates with active Rac1 in cardiomyocytes; Mena knockdown increases Rac1 activity and alters connexin 43 (Cx43) expression, localization, and trafficking at the intercalated disc, resulting in faster intercellular communication; constitutively active Rac1 overexpression increases Mena expression and causes lateral redistribution of Cx43. Co-immunoprecipitation of Mena–Rac1, Rac1 activity pull-down assay, RNAi knockdown with Cx43 localization and dye transfer assays, constitutively active Rac1 mouse model American journal of physiology. Heart and circulatory physiology Medium 24186093
2011 Genetic deletion of Mena in adult mice causes cardiac dysfunction with reduced fractional shortening, prolonged PR and QRS intervals, disrupted intercalated disc ultrastructure, mislocalization of connexin 43 to lateral cardiomyocyte borders, increased Cx43 expression, and reduced vinculin. Mena knockout mouse model, echocardiography, ECG, optical mapping, electron microscopy, immunofluorescence American journal of physiology. Heart and circulatory physiology High 21335464
2014 MENA knockdown in hepatocellular carcinoma cells decreases RhoA activity (measured by pull-down assay), reduces filopodia and stress fibers, and suppresses migration and invasion; ROCK inhibition diminishes the difference between MENA knockdown and control cells, placing MENA upstream of RhoA–ROCK in promoting HCC motility. shRNA knockdown, RhoA activity pull-down assay, ROCK inhibitor epistasis, transwell migration and invasion assay Experimental cell research Medium 24859350
2015 A thioredoxin-fold protein Sh3bgr specifically localizes to the Z-line in mature sarcomeres and regulates localization of Enah for sarcomere formation; morpholino knockdown of sh3bgr in Xenopus disrupts sarcomere formation and Enah localization, while Sh3bgr overexpression causes abnormal sarcomere assembly. Morpholino knockdown in Xenopus, rescue experiments, immunofluorescence localization of Enah Developmental biology Medium 26116879
2019 TES interacts with Mena (identified by immunoprecipitation-based mass spectrometry) and inhibits the interaction of Mena with Lamellipodin (Lpd); TES suppresses GC cell migration and invasion in a Mena-dependent fashion. Immunoprecipitation–mass spectrometry, co-IP to map TES–Mena–Lpd complex, siRNA epistasis (TES effect abolished by Mena knockdown) Cancer communications Medium 30728082

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Mena, a relative of VASP and Drosophila Enabled, is implicated in the control of microfilament dynamics. Cell 574 8861907
1999 Mena is required for neurulation and commissure formation. Neuron 346 10069337
2001 Cdc42 induces filopodia by promoting the formation of an IRSp53:Mena complex. Current biology : CB 326 11696321
1996 Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men--a clinical research center study. The Journal of clinical endocrinology and metabolism 324 8855787
2008 A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis. Developmental cell 231 19081071
1997 The WW domain of neural protein FE65 interacts with proline-rich motifs in Mena, the mammalian homolog of Drosophila enabled. The Journal of biological chemistry 208 9407065
2000 cAMP-dependent protein kinase phosphorylation of EVL, a Mena/VASP relative, regulates its interaction with actin and SH3 domains. The Journal of biological chemistry 159 10945997
2011 Mena invasive (MenaINV) promotes multicellular streaming motility and transendothelial migration in a mouse model of breast cancer. Journal of cell science 153 21670198
2004 Myosin X transports Mena/VASP to the tip of filopodia. Biochemical and biophysical research communications 143 15158464
2007 Synaptopodin protects against proteinuria by disrupting Cdc42:IRSp53:Mena signaling complexes in kidney podocytes. The American journal of pathology 142 17569780
2006 Genetic ablation of zyxin causes Mena/VASP mislocalization, increased motility, and deficits in actin remodeling. The Journal of cell biology 138 16505170
1998 Menaquinone (vitamin K2) biosynthesis: localization and characterization of the menA gene from Escherichia coli. Journal of bacteriology 114 9573170
2003 IRSp53 is colocalised with WAVE2 at the tips of protruding lamellipodia and filopodia independently of Mena. Journal of cell science 113 12734400
2008 Identification of invasion specific splice variants of the cytoskeletal protein Mena present in mammary tumor cells during invasion in vivo. Clinical & experimental metastasis 105 18985426
2012 Splicing program of human MENA produces a previously undescribed isoform associated with invasive, mesenchymal-like breast tumors. Proceedings of the National Academy of Sciences of the United States of America 100 23129656
2003 Complex formation between the postsynaptic scaffolding protein gephyrin, profilin, and Mena: a possible link to the microfilament system. The Journal of neuroscience : the official journal of the Society for Neuroscience 98 12967995
2020 Human umbilical cord mesenchymal stem cells-derived exosomes deliver microRNA-375 to downregulate ENAH and thus retard esophageal squamous cell carcinoma progression. Journal of experimental & clinical cancer research : CR 95 32698859
2001 N-WASP, WAVE and Mena play different roles in the organization of actin cytoskeleton in lamellipodia. Journal of cell science 88 11282031
1996 Assessment of growth hormone (GH) secretion in men with adult-onset GH deficiency compared with that in normal men--a clinical research center study. The Journal of clinical endocrinology and metabolism 85 8550799
2003 Abl interactor 1 promotes tyrosine 296 phosphorylation of mammalian enabled (Mena) by c-Abl kinase. The Journal of biological chemistry 84 12672821
2004 Mena and vasodilator-stimulated phosphoprotein are required for multiple actin-dependent processes that shape the vertebrate nervous system. The Journal of neuroscience : the official journal of the Society for Neuroscience 83 15371503
2006 The cytoskeleton regulatory protein hMena (ENAH) is overexpressed in human benign breast lesions with high risk of transformation and human epidermal growth factor receptor-2-positive/hormonal receptor-negative tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 80 16533770
2016 Macrophage-dependent tumor cell transendothelial migration is mediated by Notch1/MenaINV-initiated invadopodium formation. Scientific reports 78 27901093
2007 Molecular cloning of hMena (ENAH) and its splice variant hMena+11a: epidermal growth factor increases their expression and stimulates hMena+11a phosphorylation in breast cancer cell lines. Cancer research 78 17363586
2006 Unusual splicing events result in distinct Xin isoforms that associate differentially with filamin c and Mena/VASP. Experimental cell research 78 16631741
2004 Human Mena protein, a serex-defined antigen overexpressed in breast cancer eliciting both humoral and CD8+ T-cell immune response. International journal of cancer 78 15027125
2019 Scaffold stiffness influences breast cancer cell invasion via EGFR-linked Mena upregulation and matrix remodeling. Matrix biology : journal of the International Society for Matrix Biology 77 31323325
1999 Effects of a soy milk supplement on plasma cholesterol levels and oxidative DNA damage in men--a pilot study. European journal of nutrition 75 10443336
2011 Mena invasive (Mena(INV)) and Mena11a isoforms play distinct roles in breast cancer cell cohesion and association with TMEM. Clinical & experimental metastasis 70 21484349
2010 Mena deficiency delays tumor progression and decreases metastasis in polyoma middle-T transgenic mouse mammary tumors. Breast cancer research : BCR 70 21108830
2007 Tes, a specific Mena interacting partner, breaks the rules for EVH1 binding. Molecular cell 61 18158903
2011 Hereditary breast cancer in Middle Eastern and North African (MENA) populations: identification of novel, recurrent and founder BRCA1 mutations in the Tunisian population. Molecular biology reports 60 21603858
2008 Human Mena+11a isoform serves as a marker of epithelial phenotype and sensitivity to epidermal growth factor receptor inhibition in human pancreatic cancer cell lines. Clinical cancer research : an official journal of the American Association for Cancer Research 60 18676769
2013 Endophilin, Lamellipodin, and Mena cooperate to regulate F-actin-dependent EGF-receptor endocytosis. The EMBO journal 57 24076656
2020 Arp2/3 and Mena/VASP Require Profilin 1 for Actin Network Assembly at the Leading Edge. Current biology : CB 52 32470361
2020 Hypoxia-induced TGF-β-RBFOX2-ESRP1 axis regulates human MENA alternative splicing and promotes EMT in breast cancer. NAR cancer 49 33089214
2012 Mena binds α5 integrin directly and modulates α5β1 function. The Journal of cell biology 48 22908313
2000 Differences in reproductive endocrinology between Asian men and Caucasian men--a literature review. Asian journal of andrology 46 11228931
2004 High affinity, paralog-specific recognition of the Mena EVH1 domain by a miniature protein. Journal of the American Chemical Society 44 14709031
2001 Distribution, cellular localization, and postnatal development of VASP and Mena expression in mouse tissues. Histochemistry and cell biology 44 11810195
2016 MenaINV dysregulates cortactin phosphorylation to promote invadopodium maturation. Scientific reports 42 27824079
2017 A Requirement for Mena, an Actin Regulator, in Local mRNA Translation in Developing Neurons. Neuron 41 28735747
2015 Mena-GRASP65 interaction couples actin polymerization to Golgi ribbon linking. Molecular biology of the cell 40 26538023
2016 MENA Confers Resistance to Paclitaxel in Triple-Negative Breast Cancer. Molecular cancer therapeutics 36 27811011
2015 PTP1B-dependent regulation of receptor tyrosine kinase signaling by the actin-binding protein Mena. Molecular biology of the cell 35 26337385
2013 Mena/VASP and αII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy. Cell communication and signaling : CCS 33 23937664
2019 Novel MenA Inhibitors Are Bactericidal against Mycobacterium tuberculosis and Synergize with Electron Transport Chain Inhibitors. Antimicrobial agents and chemotherapy 32 30962346
2016 HIF-2α mediates a marked increase in migration and stemness characteristics in a subset of glioma cells under hypoxia by activating an Oct-4/Sox-2-Mena (INV) axis. The international journal of biochemistry & cell biology 31 26923292
2011 WAVE2, N-WASP, and Mena facilitate cell invasion via phosphatidylinositol 3-kinase-dependent local accumulation of actin filaments. Journal of cellular biochemistry 31 21769917
2019 PTBP1 enhances exon11a skipping in Mena pre-mRNA to promote migration and invasion in lung carcinoma cells. Biochimica et biophysica acta. Gene regulatory mechanisms 29 31075540
2017 al mena: a comprehensive resource of human genetic variants integrating genomes and exomes from Arab, Middle Eastern and North African populations. Journal of human genetics 29 28638141
2016 Constitutive expression of PPARγ inhibits proliferation and migration of gastric cancer cells and down-regulates Wnt/β-Catenin signaling pathway downstream target genes TERT and ENAH. Gene 29 26956036
2013 The possible role of Mena protein and its splicing-derived variants in embryogenesis, carcinogenesis, and tumor invasion: a systematic review of the literature. BioMed research international 29 23956979
2000 Recruitment of the Arp2/3 complex and mena for the stimulation of actin polymerization in growth cones by nerve growth factor. Journal of neuroscience research 29 10797548
2019 Hepatitis B Virus Molecular Epidemiology, Host-Virus Interaction, Coinfection, and Laboratory Diagnosis in the MENA Region: An Update. Pathogens (Basel, Switzerland) 28 31083509
2015 Characterization of the expression of the pro-metastatic Mena(INV) isoform during breast tumor progression. Clinical & experimental metastasis 28 26680363
2014 HIV incidence and risk factors in Chinese young men who have sex with men--a prospective cohort study. PloS one 28 24878586
2022 Native proline-rich motifs exploit sequence context to target actin-remodeling Ena/VASP protein ENAH. eLife 26 35076015
2018 Effects of Substitution, and Adding of Carbohydrate and Fat to Whey-Protein on Energy Intake, Appetite, Gastric Emptying, Glucose, Insulin, Ghrelin, CCK and GLP-1 in Healthy Older Men-A Randomized Controlled Trial. Nutrients 26 29360778
2016 5'-Inositol phosphatase SHIP2 recruits Mena to stabilize invadopodia for cancer cell invasion. The Journal of cell biology 26 27597754
2014 Acute effects of pea protein and hull fibre alone and combined on blood glucose, appetite, and food intake in healthy young men--a randomized crossover trial. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme 26 25302637
2019 Circular RNA hsa_circ_0030018 acts as a sponge of miR-599 to aggravate esophageal carcinoma progression by regulating ENAH expression. Journal of cellular biochemistry 25 31736156
2023 Matrix stiffness regulates tumor cell intravasation through expression and ESRP1-mediated alternative splicing of MENA. Cell reports 24 37027295
2020 The Spectrum of Mutations of Homocystinuria in the MENA Region. Genes 24 32245022
2019 Epidemiological and genetic characterization of pH1N1 and H3N2 influenza viruses circulated in MENA region during 2009-2017. BMC infectious diseases 24 30971204
2006 Characterization of human Enah gene. Biochimica et biophysica acta 24 16494957
2017 Novel long-chain compounds with both immunomodulatory and MenA inhibitory activities against Staphylococcus aureus and its biofilm. Scientific reports 23 28071679
2017 Association between promoter methylation of MLH1 and MSH2 and reactive oxygen species in oligozoospermic men-A pilot study. Andrologia 23 28983945
2016 The alternatively-included 11a sequence modifies the effects of Mena on actin cytoskeletal organization and cell behavior. Scientific reports 22 27748415
2014 Dynamin1 is a novel target for IRSp53 protein and works with mammalian enabled (Mena) protein and Eps8 to regulate filopodial dynamics. The Journal of biological chemistry 22 25031323
2014 Gastric cancer in young vs old Romanian patients: immunoprofile with emphasis on maspin and mena protein reactivity. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 21 25556597
2012 MENA is a transcriptional target of the Wnt/beta-catenin pathway. PloS one 21 22615875
2023 Current and future trends in heat-related mortality in the MENA region: a health impact assessment with bias-adjusted statistically downscaled CMIP6 (SSP-based) data and Bayesian inference. The Lancet. Planetary health 20 37019569
2022 Enabled homolog (ENAH) regulated by RNA binding protein splicing factor 3b subunit 4 (SF3B4) exacerbates the proliferation, invasion and migration of hepatocellular carcinoma cells via Notch signaling pathway. Bioengineered 20 35030977
2009 The immunohistochemical aspects of protein Mena in cervical lesions. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie 20 19434313
2008 The expression of cytoskeleton regulatory protein Mena in colorectal lesions. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie 20 18758639
2020 Dietary Intake of Carotenoid-Rich Vegetables Reduces Visceral Adiposity in Obese Japanese men-A Randomized, Double-Blind Trial. Nutrients 19 32764462
2012 Mena, a new available marker in tumors of salivary glands? European journal of histochemistry : EJH 19 22472896
2019 Characterization of MenA (isoprenyl diphosphate:1,4-dihydroxy-2-naphthoate isoprenyltransferase) from Mycobacterium tuberculosis. PloS one 16 30978223
2017 Mammalian-enabled (MENA) protein enhances oncogenic potential and cancer stem cell-like phenotype in hepatocellular carcinoma cells. FEBS open bio 16 28781954
2009 Human Mena associates with Rac1 small GTPase in glioblastoma cell lines. PloS one 16 19277120
2004 Increased noise sensitivity and altered inner ear MENA distribution in VASP-/- mice. Cell and tissue research 16 15578270
2024 Beneficial effects of exercise, testosterone, vitamin D, calcium and protein in older men-A randomized clinical trial. Journal of cachexia, sarcopenia and muscle 15 38890228
2012 First National Report on Aminotransaminases' Percentiles in Children of the Middle East and North Africa (MENA): the CASPIAN-III Study. Hepatitis monthly 15 23346152
2011 Mammalian enabled (Mena) is a critical regulator of cardiac function. American journal of physiology. Heart and circulatory physiology 15 21335464
2014 Microfilament regulatory protein MENA increases activity of RhoA and promotes metastasis of hepatocellular carcinoma. Experimental cell research 14 24859350
2022 LncRNA ZFAS1 promotes laryngeal cancer progression through RBFOX2-mediated MENA alternative splicing. Environmental toxicology 13 36336961
2019 TES functions as a Mena-dependent tumor suppressor in gastric cancer carcinogenesis and metastasis. Cancer communications (London, England) 13 30728082
2017 The Satiating Properties of Pork are not Affected by Cooking Methods, Sousvide Holding Time or Mincing in Healthy Men-A Randomized Cross-Over Meal Test Study. Nutrients 13 28846600
2015 A thioredoxin fold protein Sh3bgr regulates Enah and is necessary for proper sarcomere formation. Developmental biology 13 26116879
2010 HYSCORE evidence that endogenous mena- and ubisemiquinone bind at the same Q site (Q(D)) of Escherichia coli nitrate reductase A. Journal of the American Chemical Society 13 20387886
2002 NDPP1 is a novel CARD domain containing protein which can inhibit apoptosis and suppress NF-kappaB activation. International journal of oncology 13 11956601
2022 Pancreatic cancer in the MENA region, a bibliometric review. Ecancermedicalscience 12 35702406
2016 MENA Promotes Tumor-Intrinsic Metastasis through ECM Remodeling and Haptotaxis. Cancer discovery 12 27138561
2000 Estrogen receptor content in malignant breast tumors in men--a review. Journal of mammary gland biology and neoplasia 12 14973390
2013 Mena associates with Rac1 and modulates connexin 43 remodeling in cardiomyocytes. American journal of physiology. Heart and circulatory physiology 11 24186093
2012 Clinical significance of Mena and Her-2 expression in breast cancer. European journal of gynaecological oncology 10 23185786
2022 Mutational spectrum of BRCA1/2 genes in Moroccan patients with hereditary breast and/or ovarian cancer, and review of BRCA mutations in the MENA region. Breast cancer research and treatment 9 35578052
2016 Isolation and characterization of mutants corresponding to the MENA, MENB, MENC and MENE enzymatic steps of 5'-monohydroxyphylloquinone biosynthesis in Chlamydomonas reinhardtii. The Plant journal : for cell and molecular biology 9 27612091
2024 Upregulation of ENAH by a PI3K/AKT/β-catenin cascade promotes oral cancer cell migration and growth via an ITGB5/Src axis. Cellular & molecular biology letters 8 39511483

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