Affinage

EPB41L3

Band 4.1-like protein 3 · UniProt Q9Y2J2

Length
1087 aa
Mass
120.7 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: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EPB41L3 (protein 4.1B/DAL-1) is a FERM-domain membrane-cytoskeleton adaptor that organizes specialized plasma-membrane microdomains at cell-cell contacts and along myelinated axons, and acts as a tumor suppressor across multiple epithelial lineages (PMID:12234973, PMID:15688033, PMID:21966409, PMID:17640904). It is localized at sites of cell-cell contact and links transmembrane partners to the actin-spectrin cytoskeleton; complex formation with the adhesion molecule TSLC1/CADM1 depends on an intact actin network, and crystallography places this interaction in a hydrophobic pocket of the FERM C-lobe contacting TSLC1 residues Tyr406/Thr408 (PMID:12234973, PMID:21131357). In the nervous system, 4.1B binds the GNP motifs of Caspr at paranodes and Caspr2 at juxtaparanodes, where it is required to target Caspr2 and cluster Kv1 channels and to generate the paranodal membrane barrier; 4.1B-null mice show paranodal/juxtaparanodal disorganization, reduced βII-spectrin enrichment, axonal hyperexcitability, and altered myelin sheath thickness (PMID:12542678, PMID:20164332, PMID:21966409, PMID:23109359, PMID:26840208). Through its plasma-membrane-localized U2 domain, 4.1B suppresses growth by activating sequential Src-Rac1-JNK signaling, inducing G1 arrest with reduced cyclin A and Rb phosphorylation, and it restrains EGFR by binding the receptor juxtamembrane segment to block dimerization and downstream MAPK and PI3K/AKT signaling (PMID:15688033, PMID:16707455, PMID:16007173, PMID:31492173). 4.1B also controls actin stress-fiber organization, adhesion, and motility in an isoform-specific manner, with the 130 kDa plasma-membrane isoform required for spreading and stress-fiber formation (PMID:24381168, PMID:17264155). Loss of 4.1B promotes transformation and tumor progression in vivo, including increased susceptibility to prostate carcinoma and enhanced metastatic propensity (PMID:17640904, PMID:27312663). Biallelic loss-of-function variants in EPB41L3 cause an autosomal recessive developmental disorder with seizures, hypotonia, and delayed myelination (PMID:39292993).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2000 High

    Established that 4.1B is positioned at cell-cell contact sites and that splice isoforms diverge functionally in their cytoskeletal-binding capacity, framing it as a membrane adaptor with isoform-specific roles.

    Evidence Immunofluorescence, cDNA characterization, and domain analysis across tissues

    PMID:10652311

    Open questions at the time
    • Did not identify the transmembrane binding partner at contacts
    • Functional consequence of isoform heterogeneity untested
  2. 2002 High

    Answered what 4.1B binds at cell-cell contacts by showing a direct, actin-dependent complex with the tumor suppressor TSLC1/CADM1, linking adhesion to the cytoskeleton.

    Evidence Co-IP, colocalization, and actin-disruption experiments

    PMID:12234973

    Open questions at the time
    • Structural basis of binding not resolved
    • Did not establish how the complex suppresses growth
  3. 2010 High

    Resolved the atomic basis of the TSLC1 interaction, mapping it to a hydrophobic FERM C-lobe pocket and defining the critical TSLC1 contact residues.

    Evidence X-ray crystallography of the FERM–TSLC1 complex with SPR validation

    PMID:21131357

    Open questions at the time
    • Structure of other partner complexes (Caspr, EGFR, integrin) not solved
    • In vivo relevance of specific contacts not tested
  4. 2003 High

    Extended 4.1B function to myelinated axons by showing direct binding to the GNP motifs of Caspr and Caspr2, implicating it in axonal domain organization.

    Evidence Co-IP from brain homogenate and in vitro binding assays

    PMID:12542678

    Open questions at the time
    • Did not test whether binding is required for axonal compartmentalization in vivo
  5. 2004 High

    Identified 4.1B as a regulator of arginine methyltransferases, binding PRMT3 without being a substrate and inhibiting its methylation of GAR substrates.

    Evidence Yeast two-hybrid, co-IP, in vitro and cellular methylation assays

    PMID:15334060

    Open questions at the time
    • Biological consequence of PRMT3 inhibition not linked to a phenotype
    • Methylation substrates relevant in vivo unknown
  6. 2005 High

    Defined the U2 domain at the plasma membrane as necessary and sufficient for meningioma growth suppression, localizing the tumor-suppressor activity to a discrete module.

    Evidence Truncation/deletion constructs with clonogenic, proliferation, and apoptosis readouts and membrane-targeting fusions

    PMID:15688033

    Open questions at the time
    • Downstream effectors of U2 not yet identified
    • Mechanism of membrane requirement unresolved at this stage
  7. 2006 High

    Linked the U2/membrane-dependent growth suppression to a defined signaling cascade, showing sequential Src-Rac1-JNK activation drives cyclin A regulation.

    Evidence Genetic and pharmacologic inhibition, dominant-negatives, JNK activity and cyclin A assays

    PMID:16707455

    Open questions at the time
    • How U2 at the membrane initiates Src activation is unknown
    • Generality of the pathway across cancer types untested
  8. 2010 High

    Demonstrated genetically that 4.1B is required in vivo for juxtaparanodal Caspr2 accumulation, Kv1 clustering, and the paranodal membrane barrier.

    Evidence Transgenic 4.1-binding-deficient rescue constructs in 4.1B-null mice with immunofluorescence

    PMID:20164332

    Open questions at the time
    • Did not distinguish targeting from stabilization
    • Effect on conduction not directly measured here
  9. 2011 High

    Multiple 4.1B-null mouse analyses established that loss disrupts paranodal septate junctions, juxtaparanodal Kv1/Caspr2 clustering, βII-spectrin enrichment, axon caliber, and causes neuronal hyperexcitability cell-autonomously.

    Evidence 4.1B-null mice with immunofluorescence, immuno-EM, electrophysiology, and myelinating co-cultures

    PMID:21632923 PMID:21958379 PMID:21966409

    Open questions at the time
    • Molecular mechanism connecting 4.1B loss to myelin/caliber changes incomplete
  10. 2013 High

    Resolved isoform specificity in adhesion/motility by showing the 130 kDa plasma-membrane isoform, not the 60 kDa form, is required for stress-fiber formation, spreading, and migration.

    Evidence Isoform-specific rescue in 4.1B-KO MEFs with adhesion/spreading/migration assays

    PMID:24381168

    Open questions at the time
    • Direct cytoskeletal effector engaged by the 130 kDa isoform not defined
  11. 2019 Medium

    Defined a direct molecular mechanism for receptor-level tumor suppression: 4.1B FERM binds the EGFR juxtamembrane segment to block dimerization, autophosphorylation, and MAPK/PI3K signaling.

    Evidence Co-IP, domain mapping, EGFR phosphorylation/dimerization assays, KO MEFs and gastric cancer cells

    PMID:31492173

    Open questions at the time
    • Structural model of FERM–EGFR contact absent
    • Single-lab data without reciprocal structural validation
  12. 2024 High

    Connected EPB41L3 to human disease, showing biallelic loss-of-function causes an autosomal recessive developmental disorder with seizures and delayed myelination, with supporting oligodendroglial defects in mice.

    Evidence Exome sequencing, patient fibroblast protein/transcript analysis, and Epb41l3-KO oligodendroglia culture

    PMID:39292993

    Open questions at the time
    • Mechanistic link between 4.1B loss and oligodendroglial apoptosis incomplete
    • Genotype-phenotype range across patients limited

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the membrane-localized U2 domain physically initiates Src activation and integrates the diverse partner interactions (TSLC1, Caspr/Caspr2, EGFR, integrin) into a unified growth-suppressive and cytoskeletal program remains unresolved.
  • No structural model of U2-mediated signaling
  • Unclear which interactions are most relevant to the human disease phenotype

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005856 cytoskeleton 3 GO:0005634 nucleus 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 2 R-HSA-1643685 Disease 2 R-HSA-1640170 Cell Cycle 1
Partners
CADM1CDH1CNTNAP1CNTNAP2EGFRITGB8PRMT3PRMT5

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 DAL-1/4.1B (EPB41L3) directly associates with the tumor suppressor TSLC1 (CADM1) at cell-cell contact sites, and this complex interacts with the actin filament cytoskeleton; the complex formation is dependent on the integrity of the actin cytoskeleton. Co-immunoprecipitation, colocalization imaging, actin disruption experiments Cancer research High 12234973
2010 Crystal structure of the DAL-1/4.1B FERM domain in complex with the TSLC1 cytoplasmic domain reveals that binding occurs through a hydrophobic pocket in the C-lobe of the FERM domain; Tyr406 and Thr408 of TSLC1 form the critical contacts, confirmed by surface plasmon resonance. X-ray crystallography, surface plasmon resonance The Journal of biological chemistry High 21131357
2000 Protein 4.1B is localized specifically at the plasma membrane in regions of cell-cell contact; multiple splice isoforms exist with functionally relevant heterogeneity in the spectrin-actin binding and NuMA binding domains; only muscle isoforms possess a functional spectrin-actin binding domain. Immunofluorescence, Western blot, cDNA characterization, in situ hybridization The Journal of biological chemistry High 10652311
2003 Protein 4.1B binds to the conserved intracellular GNP motifs of both Caspr/paranodin (at paranodes) and Caspr2 (at juxtaparanodes) of myelinated axons, as demonstrated by co-immunoprecipitation from brain homogenates and progressive accumulation during postnatal development. Co-immunoprecipitation from brain homogenate, in vitro binding assay, immunohistochemistry The European journal of neuroscience High 12542678
2010 Protein 4.1B is required for Caspr2 accumulation at the juxtaparanodal region (JXP) and for Kv1 channel clustering there; the interaction of Caspr with 4.1B is necessary for generating an efficient membrane barrier at the paranodal junction; Caspr2 and Kv1 channels are not clustered at JXP in 4.1B-null mice. Transgenic rescue experiments (Caspr-d4.1 and Caspr2-d4.1 mutants in null mice), immunofluorescence, 4.1B-null mouse analysis The Journal of neuroscience High 20164332
2004 DAL-1/4.1B interacts with protein arginine N-methyltransferase 3 (PRMT3) via the C-terminal catalytic core domain of PRMT3 and the FERM domain of DAL-1/4.1B; DAL-1/4.1B is not a PRMT3 substrate but inhibits PRMT3-mediated methylation of GAR-containing substrates in vitro and in cells. Yeast two-hybrid, co-immunoprecipitation, in vitro binding assay (GST pulldown), in vitro methylation assay, induced expression in MCF-7 cells Oncogene High 15334060
2002 DAL-1/4.1B interacts with 14-3-3 isoforms (β, γ, η) via residues Pro244–Leu280 within its FERM domain; this interaction is specific to DAL-1/4.1B and is not shared by merlin, ezrin, or radixin. Yeast two-hybrid, GST affinity chromatography, co-immunoprecipitation The Biochemical journal High 11996670
2004 Disruption of 14-3-3 binding to DAL-1/4.1B (via F359Y mutation) does not impair DAL-1 growth suppressor function in meningioma cells, indicating 14-3-3 binding is not required for growth suppression. Site-directed mutagenesis, GST affinity chromatography, co-immunoprecipitation, clonogenic assay, thymidine incorporation Oncogene High 15116094
2005 The U2 domain of protein 4.1B, when localized to the plasma membrane, is necessary and sufficient for meningioma growth suppression; deletion of U2 domain eliminates growth suppressor function; artificial membrane targeting of U2 alone recapitulates full-length DAL-1 suppression. Truncation/deletion constructs, clonogenic assay, thymidine incorporation, caspase-3 activation, membrane localization signal fusion Oncogene High 15688033
2006 Protein 4.1B/DAL-1 growth suppression in meningioma cells requires the sequential activation of Src, Rac1, and JNK; inhibition of Rac1 or JNK abrogates 4.1B-mediated growth suppression and cyclin A regulation; this pathway requires the U2 domain localized to the plasma membrane. Genetic and pharmacologic inhibition of Src, Rac1, JNK; dominant-negative constructs; clonogenic assay; JNK activity assay; cyclin A analysis Cancer research High 16707455
2005 DAL-1/4.1B modulates PRMT5 activity in a substrate-specific manner: it inhibits PRMT5-mediated methylation of Sm proteins but enhances methylation of myelin basic protein. Yeast two-hybrid, in vitro methylation assay, cell-based methylation assay Biochemical and biophysical research communications Medium 15737618
2006 DAL-1/4.1B-induced apoptosis in MCF-7 breast cancer cells is primarily mediated through activation of caspase-8; inhibition of caspase-8 activation blocks DAL-1/4.1B-induced cell death; protein methylation cooperates in this apoptotic pathway. Flow cytometry, caspase activation assays, methylation inhibitor (AdOX) treatment Molecular cancer Medium 16420693
2005 Protein 4.1B interacts selectively with the β8 integrin cytoplasmic tail via its C-terminal domain; this interaction was identified in cultured astrocytes and brain tissue. Yeast two-hybrid, co-immunoprecipitation, colocalization by immunofluorescence Proceedings of the National Academy of Sciences Medium 16157875
2009 Protein 4.1B acts as an intracellular effector of SynCAM1 to recruit NMDA-type receptors to SynCAM1 adhesion sites; 4.1B in conjunction with SynCAM1 increases NMDAR-mediated mEPSC frequency and presynaptic contact area; manipulation of 4.1B levels in hippocampal neurons specifically affects NMDAR-mediated activity and localization. Co-immunoprecipitation, COS7 cell reconstitution assay, HEK293/neuron co-culture electrophysiology, hippocampal neuron knockdown/overexpression Molecular and cellular neurosciences High 19796685
2009 A 200 kDa isoform of protein 4.1B is specifically associated with the Golgi apparatus; depletion of this Golgi-specific 4.1B by siRNA disrupts Golgi structure and prevents Na+/K+-ATPase, ZO-1, and ZO-2 from migrating to the plasma membrane. siRNA knockdown, Brefeldin A treatment, immunofluorescence, fractionation, Western blot Journal of cell science High 19299464
2011 4.1B-null mice show mislocalization of Caspr at paranodes, destabilization of paranodal axoglial septate junctions in both PNS and CNS, and progressive disruption of paranodal ultrastructure; the 4.1B locus generates multiple splice isoforms differentially in PNS vs. CNS. 4.1B-null mouse generation, immunofluorescence, electron microscopy, RT-PCR for splice isoforms The Journal of neuroscience High 21632923
2011 4.1B KO mice show loss of proper molecular compartmentalization at the axon initial segment region: the Caspr+ para-AIS barrier is disrupted, preventing proper segregation and compartmentalization of Kv1 channels. 4.1B KO mouse immunofluorescence, confocal analysis of AIS compartments BMC biology Medium 21958379
2011 In 4.1B KO mice, Caspr/paranodin distribution and levels are decreased at paranodal regions, Caspr2/TAG-1/Kv1.1 enrichment is absent at juxtaparanodes, βII spectrin enrichment along the axolemma is decreased, axon calibers are reduced, and electrophysiological recordings show neuronal hyperexcitability; these defects are neuron-autonomous. 4.1B KO mouse, immunofluorescence, immuno-EM, electrophysiology, myelinating co-culture with WT Schwann cells and 4.1B-null neurons PloS one High 21966409
2012 4.1B is expressed subjacent to the axon membrane in all myelinated axon domains except nodes; in 4.1B-deficient mice, juxtaparanodal Kv1/Caspr2 clustering is substantially disrupted in both PNS and CNS; loss of 4.1B in axons is associated with reduced internodal Necl-1, Necl-2, and α-2 spectrin; and 4.1B unexpectedly regulates myelin sheath thickness. Immunofluorescence, immuno-EM, 4.1B KO mouse, myelinating co-culture (neuron-autonomous test), nerve conduction velocity measurement Glia High 23109359
2013 The 130 kDa isoform of protein 4.1B, localized predominantly at the plasma membrane, is required for cell adhesion, spreading, and migration in mouse embryonic fibroblasts; loss of 130 kDa 4.1B causes failure to form actin stress fibers; rescue with 130 kDa but not 60 kDa 4.1B restores spreading and stress fiber formation. 4.1B KO MEF cells, re-expression of specific isoforms, immunofluorescence, adhesion/spreading/migration assays The Journal of biological chemistry High 24381168
2001 DAL-1 suppresses cell proliferation in meningioma cells but not schwannoma cells; DAL-1 interacts with ERM proteins and βII-spectrin but not with the merlin-interactor SCHIP-1. Cell proliferation assays, co-immunoprecipitation Neurobiology of disease Medium 11300722
2002 Expression of DAL-1 in MCF-7 breast cancer cells suppresses cell growth partly through induction of apoptosis, and increases cell attachment to extracellular matrix substrates. Constitutive and inducible expression in MCF-7 cells, proliferation assays, apoptosis assays, attachment assays International journal of cancer Medium 12115567
2007 Knockdown of 4.1B in non-metastatic sarcoma cells by RNAi causes loss of actin stress fibers and doubles cell migration speed; forced expression of 4.1B in metastatic cells halves migration speed and suppresses chemotaxis, implicating 4.1B in regulation of actin cytoskeleton and cell motility. RNAi knockdown, overexpression, F-actin staining, cell migration/chemotaxis assays Journal of cell science Medium 17264155
2007 4.1B-deficient mice display increased susceptibility to aggressive, spontaneous prostate carcinomas with reduced apoptosis; downregulation of 4.1B in poorly metastatic prostate cancer cells increases their metastatic propensity in an orthotopic model. 4.1B KO mouse, orthotopic prostate cancer model, histopathology, apoptosis assay Proceedings of the National Academy of Sciences High 17640904
2005 4.1B expression is dramatically upregulated in mammary epithelial cells during pregnancy; 4.1B-null mice show increased mammary epithelial cell proliferation during pregnancy; 4.1B induces G1 cell cycle arrest with decreased cyclin A, reduced Rb phosphorylation, and reduced erbB2 phosphorylation in mammary epithelial cell lines. 4.1B KO mouse mammary gland analysis, in vitro cell cycle analysis (FACS), Western blot for cyclin A, Rb, erbB2 phosphorylation, immunohistochemistry Oncogene High 16007173
2010 EPB41L3 (4.1B) functions as a tumor suppressor in ovarian cancer; reexpression in 3D spheroid models causes growth suppression and induces apoptosis; chromosome 18 transfer including EPB41L3 induces neoplastic suppression in TOV21G ovarian cancer cells. Microcell-mediated chromosome transfer, gene expression microarray, immunoblot, immunohistochemistry, 3D spheroid growth assay, electron microscopy, inducible expression Neoplasia Medium 20651987
2007 p55 (membrane-associated guanylate kinase), protein 4.1B, and sodium bicarbonate cotransporter 1 (NBC1) form a molecular complex at the basolateral membrane of renal S1-S2 proximal tubules, as shown by co-immunoprecipitation and GST pulldown. Co-immunoprecipitation with anti-p55 and anti-4.1B antibodies, GST pulldown with NBC1 and 4.1B regions, immunohistochemistry The journal of histochemistry and cytochemistry Medium 17712176
2011 β8 integrin and Band 4.1B cooperatively regulate cardiac morphogenesis; double-null embryos for β8 integrin and 4.1B show cardiovascular defects and death by E11.5, with defective cardiac outflow tract development and reduced smooth muscle α-actin in neural crest-derived cells. Double-null mouse genetics, embryo phenotyping, immunofluorescence for SMAα-actin Developmental dynamics Medium 21181944
2016 4.1B is required for proper targeting of Caspr2 early during myelination; lateral stability of paranodal Caspr (assessed by FRAP) is not altered in 4.1B KO mice, indicating 4.1B is not required for paranodal junction assembly/stability but is needed for juxtaparanodal Caspr2 targeting. 4.1B KO mouse, myelinating DRG/Schwann cell co-culture, adenoviral Caspr-GFP expression, FRAP, immunofluorescence Glia High 26840208
2018 Combined ablation of 4.1B and Whirlin (Whrn) in double-mutant mice leads to axonal transport defects in cerebellar Purkinje neuron myelinated axons, manifested by axonal swellings containing cytoskeletal components and vesicles, and progressive impairment of locomotor performance. Single and double KO mouse, immunoblot, immunofluorescence, gait analysis Journal of neuroscience research Medium 30447021
2019 The FERM domain of protein 4.1B interacts with EGFR through the initial 13 amino acids (P13) of the intracellular juxtamembrane segment; this binding inhibits EGFR dimerization and autophosphorylation and suppresses downstream EGFR/MAPK/ERK1/2 and PI3K/AKT signaling, inhibiting gastric cancer cell proliferation. Co-immunoprecipitation, immunofluorescence colocalization, domain mapping, EGFR phosphorylation/dimerization assays, KO MEF cells, gastric cancer cell overexpression/knockdown Cell communication and signaling Medium 31492173
2015 DAL-1 directly binds E-cadherin and regulates its promoter, attenuating EMT in lung cancer; HSPA5 (GRP78) was identified as a direct DAL-1 binding protein by co-immunoprecipitation. Co-immunoprecipitation, Western blot, EMT marker analysis, promoter analysis, overexpression and knockdown Journal of experimental & clinical cancer research Medium 25609022
2017 DAL-1 suppresses HSPA5 expression at mRNA and protein levels and inhibits the PI3K/Akt/Mdm2 signaling pathway through downregulation of HSPA5; DAL-1 and HSPA5 proteins co-localize in the cytoplasm and nucleus. Co-immunoprecipitation, immunofluorescence colocalization, Western blot, qRT-PCR, migration/invasion assay Oncology reports Medium 29048640
2016 EPB41L3 suppresses esophageal squamous cell carcinoma cell invasion and migration; overexpression of EPB41L3 downregulates MMP2 and MMP9 expression and p-AKT levels. Overexpression and siRNA knockdown, wound healing and Transwell assays, Western blot for MMP2, MMP9, p-AKT Cell biochemistry and function Medium 26916087
2021 DAL-1/4.1B promotes exosome uptake in lung cancer cells via upregulation of heparan sulfate proteoglycan 2 (HSPG2); heparin and heparinase counteract the uptake enhancement by DAL-1/4.1B; HSPG2 expression correlates positively with DAL-1/4.1B levels. siRNA knockdown, overexpression, vesicle uptake inhibitors/heparinase treatment, Western blot, qRT-PCR Molecular and cellular biochemistry Low 34657240
2004 Protein 4.1B isoforms in kidney and brain arise from two alternative promoters (exons 1A and 1B) coupled to differential alternative splicing at exon 2; exon 1B transcripts encode larger 4.1B isoforms with N-terminal extension; differentiation of PC12 cells causes translocation of large 4.1B isoforms into the nucleus. Promoter mapping, RT-PCR, Western blot, PC12 differentiation with subcellular fractionation/immunofluorescence Biochimica et biophysica acta Medium 15488987
2024 Biallelic loss-of-function variants in EPB41L3 cause a human autosomal recessive developmental disorder (EADD) with seizures, hypotonia, and delayed myelination; patient fibroblasts show ablation of 4.1B protein; Epb41l3-deficient mouse oligodendroglia show reduced myelin gene expression, reduced branching, and increased apoptosis. Exome sequencing, Western blot, qRT-PCR of patient fibroblasts, NMD inhibition assay, mouse oligodendroglia KO culture with gene expression and morphological analysis Brain High 39292993
2016 Knockout of 4.1B in SV40T-immortalized mouse embryonic fibroblasts is sufficient to trigger malignant transformation, enabling tumor formation in nude mice; loss of 4.1B activates ERK, AKT, the p16INK4A-pRb pathway, and Wnt/β-catenin nuclear accumulation; 4.1B interacts with E-cadherin in MEF cells. 4.1B KO iMEF cells, tumor formation in nude mice, Western blot for ERK/AKT/Wnt pathway, co-immunoprecipitation (4.1B-E-cadherin), immunofluorescence for β-catenin Molecular carcinogenesis Medium 27312663
2022 EPB41L3 overexpression in cervical cancer cells inhibits PI3K and AKT phosphorylation, leading to apoptosis; overexpression suppresses tumorigenicity in nude mice. Lentiviral overexpression, Western blot for PI3K/AKT phosphorylation, apoptosis assay, xenograft mouse model Acta biochimica Polonica Low 35569139

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 miRNA-223 promotes gastric cancer invasion and metastasis by targeting tumor suppressor EPB41L3. Molecular cancer research : MCR 325 21628394
2002 Direct association of TSLC1 and DAL-1, two distinct tumor suppressor proteins in lung cancer. Cancer research 163 12234973
2015 MicroRNA-223 delivered by platelet-derived microvesicles promotes lung cancer cell invasion via targeting tumor suppressor EPB41L3. Molecular cancer 158 25881295
2000 Loss of DAL-1, a protein 4.1-related tumor suppressor, is an important early event in the pathogenesis of meningiomas. Human molecular genetics 151 10888600
2000 Merlin, DAL-1, and progesterone receptor expression in clinicopathologic subsets of meningioma: a correlative immunohistochemical study of 175 cases. Journal of neuropathology and experimental neurology 139 11079777
2000 Molecular and functional characterization of protein 4.1B, a novel member of the protein 4.1 family with high level, focal expression in brain. The Journal of biological chemistry 116 10652311
2003 Protein 4.1B associates with both Caspr/paranodin and Caspr2 at paranodes and juxtaparanodes of myelinated fibres. The European journal of neuroscience 114 12542678
2004 DAL-1/4.1B tumor suppressor interacts with protein arginine N-methyltransferase 3 (PRMT3) and inhibits its ability to methylate substrates in vitro and in vivo. Oncogene 97 15334060
2010 Organization of myelinated axons by Caspr and Caspr2 requires the cytoskeletal adapter protein 4.1B. The Journal of neuroscience : the official journal of the Society for Neuroscience 94 20164332
1987 Membrane skeletal alterations during in vivo mouse red cell aging. Increase in the band 4.1a:4.1b ratio. The Journal of clinical investigation 85 3805278
2011 Characterization of the axon initial segment (AIS) of motor neurons and identification of a para-AIS and a juxtapara-AIS, organized by protein 4.1B. BMC biology 79 21958379
2007 Downregulation of TSLC1 and DAL-1 expression occurs frequently in breast cancer. Breast cancer research and treatment 74 17260099
2011 Aberrant expression of tumor suppressors CADM1 and 4.1B in invasive lesions of primary breast cancer. Breast cancer (Tokyo, Japan) 68 21526423
2006 Promoter hypermethylation of the potential tumor suppressor DAL-1/4.1B gene in renal clear cell carcinoma. International journal of cancer 66 16152585
2007 Protein 4.1B suppresses prostate cancer progression and metastasis. Proceedings of the National Academy of Sciences of the United States of America 62 17640904
2004 The MADS-box gene DAL1 is a potential mediator of the juvenile-to-adult transition in Norway spruce (Picea abies). The Plant journal : for cell and molecular biology 60 15500470
2000 Type II brain 4.1 (4.1B/KIAA0987), a member of the protein 4.1 family, is localized to neuronal paranodes. Brain research. Molecular brain research 59 11146105
2001 The protein 4.1 tumor suppressor, DAL-1, impairs cell motility, but regulates proliferation in a cell-type-specific fashion. Neurobiology of disease 58 11300722
2002 Suppression of growth and increased cellular attachment after expression of DAL-1 in MCF-7 breast cancer cells. International journal of cancer 55 12115567
2011 Protein 4.1B contributes to the organization of peripheral myelinated axons. PloS one 52 21966409
2006 The tumor suppressor DAL-1/4.1B and protein methylation cooperate in inducing apoptosis in MCF-7 breast cancer cells. Molecular cancer 52 16420693
2011 The cytoskeletal adaptor protein band 4.1B is required for the maintenance of paranodal axoglial septate junctions in myelinated axons. The Journal of neuroscience : the official journal of the Society for Neuroscience 49 21632923
2017 LINC00052 upregulates EPB41L3 to inhibit migration and invasion of hepatocellular carcinoma by binding miR-452-5p. Oncotarget 46 28969024
2015 HPV33 DNA methylation measurement improves cervical pre-cancer risk estimation of an HPV16, HPV18, HPV31 and \textit{EPB41L3} methylation classifier. Cancer biomarkers : section A of Disease markers 46 26406956
2012 The 4.1B cytoskeletal protein regulates the domain organization and sheath thickness of myelinated axons. Glia 46 23109359
2009 SynCAM1 recruits NMDA receptors via protein 4.1B. Molecular and cellular neurosciences 46 19796685
2010 Microcell-mediated chromosome transfer identifies EPB41L3 as a functional suppressor of epithelial ovarian cancers. Neoplasia (New York, N.Y.) 45 20651987
2005 An interaction between {alpha}v{beta}8 integrin and Band 4.1B via a highly conserved region of the Band 4.1 C-terminal domain. Proceedings of the National Academy of Sciences of the United States of America 45 16157875
2005 Inactivation patterns of NF2 and DAL-1/4.1B (EPB41L3) in sporadic meningioma. Cancer genetics and cytogenetics 45 16213361
2002 Differential involvement of protein 4.1 family members DAL-1 and NF2 in intracranial and intraspinal ependymomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 44 12011257
1988 Correlation between protein 4.1a/4.1b ratio and erythrocyte life span. Biochimica et biophysica acta 42 3179290
2021 MADS-box transcription factors MADS11 and DAL1 interact to mediate the vegetative-to-reproductive transition in pine. Plant physiology 38 34618133
2006 Protein 4.1B/differentially expressed in adenocarcinoma of the lung-1 functions as a growth suppressor in meningioma cells by activating Rac1-dependent c-Jun-NH(2)-kinase signaling. Cancer research 35 16707455
1991 The allantoinase (DAL1) gene of Saccharomyces cerevisiae. Yeast (Chichester, England) 34 1803816
2014 Tumor suppressor role of protein 4.1B/DAL-1. Cellular and molecular life sciences : CMLS 33 25183197
2002 The 4.1/ezrin/radixin/moesin domain of the DAL-1/Protein 4.1B tumour suppressor interacts with 14-3-3 proteins. The Biochemical journal 33 11996670
2005 Loss of the putative tumor suppressor band 4.1B/Dal1 gene is dispensable for normal development and does not predispose to cancer. Molecular and cellular biology 32 16260618
2008 Potential role of EPB41L3 (protein 4.1B/Dal-1) as a target for treatment of advanced prostate cancer. Expert opinion on therapeutic targets 31 18554153
2007 Evidence for protein 4.1B acting as a metastasis suppressor. Journal of cell science 31 17264155
2004 Immunolocalization of protein 4.1B/DAL-1 during neoplastic transformation of mouse and human intestinal epithelium. Histochemistry and cell biology 31 15517334
2000 Comparison of mRNA and protein levels of four members of the protein 4.1 family: the type II brain 4.1/4.1B/KIAA0987 is the most predominant member of the protein 4.1 family in rat brain. Gene 30 10806359
2009 A Golgi-associated protein 4.1B variant is required for assimilation of proteins in the membrane. Journal of cell science 29 19299464
2005 Membrane localization of the U2 domain of Protein 4.1B is necessary and sufficient for meningioma growth suppression. Oncogene 28 15688033
2005 The tumor suppressor DAL-1/4.1B modulates protein arginine N-methyltransferase 5 activity in a substrate-specific manner. Biochemical and biophysical research communications 28 15737618
2012 Loss of expression of the differentially expressed in adenocarcinoma of the lung (DAL-1) protein is associated with metastasis of non-small cell lung carcinoma cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 27 22782504
2004 Allele-specific loss of heterozygosity at the DAL-1/4.1B (EPB41L3) tumor-suppressor gene locus in the absence of mutation. Genes, chromosomes & cancer 27 15138999
2019 Methylation of HPV 16 and EPB41L3 in oral gargles: Associations with oropharyngeal cancer detection and tumor characteristics. International journal of cancer 24 31304592
2015 Prolonged re-expression of the hypermethylated gene EPB41L3 using artificial transcription factors and epigenetic drugs. Epigenetics 24 25830725
2021 Insight into Codon Utilization Pattern of Tumor Suppressor Gene EPB41L3 from Different Mammalian Species Indicates Dominant Role of Selection Force. Cancers 23 34205890
2003 Protein 4.1B in mouse islets of Langerhans and beta-cell tumorigenesis. Histochemistry and cell biology 22 14574582
2016 Assembly of juxtaparanodes in myelinating DRG culture: Differential clustering of the Kv1/Caspr2 complex and scaffolding protein 4.1B. Glia 21 26840208
2009 Frequent concomitant epigenetic silencing of the stress-responsive tumor suppressor gene CADM1, and its interacting partner DAL-1 in nasal NK/T-cell lymphoma. International journal of cancer 21 19115211
2015 DAL-1 attenuates epithelial-to mesenchymal transition in lung cancer. Journal of experimental & clinical cancer research : CR 20 25609022
2011 β8 integrin and band 4.1B cooperatively regulate morphogenesis of the embryonic heart. Developmental dynamics : an official publication of the American Association of Anatomists 20 21181944
2010 Structural basis of tumor suppressor in lung cancer 1 (TSLC1) binding to differentially expressed in adenocarcinoma of the lung (DAL-1/4.1B). The Journal of biological chemistry 20 21131357
2004 Immunohistochemical study of protein 4.1B in the normal and W/W(v) mouse seminiferous epithelium. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 20 15150285
2018 Associations of human gene EPB41L3 DNA methylation and cervical intraepithelial neoplasia in women living with HIV-1 in Africa. AIDS (London, England) 19 30005021
2016 Epb41l3 suppresses esophageal squamous cell carcinoma invasion and inhibits MMP2 and MMP9 expression. Cell biochemistry and function 19 26916087
2007 Expression and DNA methylation patterns of Tslc1 and Dal-1 genes in hepatocellular carcinomas induced by N-nitrosodiethylamine in rats. Cancer science 19 17428255
2005 Protein 4.1B expression is induced in mammary epithelial cells during pregnancy and regulates their proliferation. Oncogene 19 16007173
2017 DAL-1 attenuates epithelial to mesenchymal transition and metastasis by suppressing HSPA5 expression in non-small cell lung cancer. Oncology reports 17 29048640
2009 Expression of the tumor suppressor genes NF2, 4.1B, and TSLC1 in canine meningiomas. Veterinary pathology 17 19429976
2020 LncRNA MAGI2-AS3 Affects Cell Invasion and Migration of Cervical Squamous Cell Carcinoma (CSCC) via Sponging miRNA-233/EPB41L3 Axis. Cancer management and research 16 32581592
2013 A 130-kDa protein 4.1B regulates cell adhesion, spreading, and migration of mouse embryo fibroblasts by influencing actin cytoskeleton organization. The Journal of biological chemistry 16 24381168
2007 Interaction of membrane skeletal protein, protein 4.1B and p55, and sodium bicarbonate cotransporter1 in mouse renal S1-S2 proximal tubules. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 16 17712176
2004 Putative tumor suppressor protein 4.1B is differentially expressed in kidney and brain via alternative promoters and 5' alternative splicing. Biochimica et biophysica acta 16 15488987
2019 miR-452 promotes the development of gastric cancer via targeting EPB41L3. Pathology, research and practice 15 31734055
2005 Mutational analysis of the DAL-1/4.1B tumour-suppressor gene locus in meningiomas. International journal of molecular medicine 15 16142420
2004 Immunoelectron microscopic localization of protein 4.1B in proximal S1 and S2 tubules of rodent kidneys. Medical electron microscopy : official journal of the Clinical Electron Microscopy Society of Japan 15 15057604
2004 Disruption of 14-3-3 binding does not impair Protein 4.1B growth suppression. Oncogene 15 15116094
2016 Aberrant expression of the candidate tumor suppressor gene DAL-1 due to hypermethylation in gastric cancer. Scientific reports 14 26923709
2007 Hypermethylation of the Dal-1 gene in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in rats. Molecular carcinogenesis 11 17415786
2005 Evolutionarily conserved coupling of transcription and alternative splicing in the EPB41 (protein 4.1R) and EPB41L3 (protein 4.1B) genes. Genomics 11 16242908
2004 Immunolocalization of protein 4.1B in the rat digestive system. Journal of molecular histology 9 15503808
2021 DAL-1/4.1B promotes the uptake of exosomes in lung cancer cells via Heparan Sulfate Proteoglycan 2 (HSPG2). Molecular and cellular biochemistry 8 34657240
2015 The targeted inhibitory effects of human amniotic fluid stem cells carrying CXCR4 promoter and DAL-1 on non-small cell lung carcinoma growth. Gene therapy 8 26280082
2001 Cis-acting sites contributing to expression of divergently transcribed DAL1 and DAL4 genes in S. cerevisiae: a word of caution when correlating cis-acting sequences with genome-wide expression analyses. Current genetics 8 11409177
2022 HDAC10 Inhibits Cervical Cancer Progression through Downregulating the HDAC10-microRNA-223-EPB41L3 Axis. Journal of oncology 7 35075362
2022 Methylation of HPV16 and EPB41L3 in oral gargles and the detection of early and late oropharyngeal cancer. Cancer medicine 7 35619332
2019 4.1B suppresses cancer cell proliferation by binding to EGFR P13 region of intracellular juxtamembrane segment. Cell communication and signaling : CCS 7 31492173
2019 Mutation and Expression of a Candidate Tumor Suppressor Gene EPB41L3 in Gastric and Colorectal Cancers. Pathology oncology research : POR 7 31828581
2019 Promoter-associated DNA methylation & expression profiling of genes (FLT 3, EPB41L3 & SFN) in patients with oral squamous cell carcinoma in the Khasi & Jaintia population of Meghalaya, India. The Indian journal of medical research 7 32048621
2016 Knockout of 4.1B triggers malignant transformation in SV40T-immortalized mouse embryo fibroblast cells. Molecular carcinogenesis 7 27312663
2015 DAL-1/4.1B contributes to epithelial-mesenchymal transition via regulation of transforming growth factor-β in lung cancer cell lines. Molecular medicine reports 7 26300315
2019 Pivotal roles of protein 4.1B/DAL‑1, a FERM‑domain containing protein, in tumor progression (Review). International journal of oncology 6 31545421
2018 MicroRNA-26a regulates ANXA1, rather than DAL-1, in the development of lung cancer. Oncology letters 6 29552220
2018 Ablation of cytoskeletal scaffolding proteins, Band 4.1B and Whirlin, leads to cerebellar purkinje axon pathology and motor dysfunction. Journal of neuroscience research 6 30447021
2009 Dispensable role of protein 4.1B/DAL-1 in rodent adrenal medulla regarding generation of pheochromocytoma and plasmalemmal localization of TSLC1. Biochimica et biophysica acta 6 19321127
2025 The MADS-box transcription factor DAL1 links age to reproductive development through regulation of LEAFY homologs in conifer. Plant physiology 5 40208195
2023 Expression and hypermethylation of JAM and EPB41L3 in cervical squamous cell carcinoma: Clinical significance and applications. Histology and histopathology 5 38213260
2022 Over-expression of EPB41L3 promotes apoptosis of human cervical carcinoma cells through PI3K/AKT signaling. Acta biochimica Polonica 5 35569139
2019 Protein 4.1B Suppresses Tumor Metastasis by Regulating Epithelial-mesenchymal Transition Progression in Melanoma Cells. International journal of medical sciences 5 31171904
2004 Protein 4.1B localizes on unmyelinated axonal membranes in the mouse enteric nervous system. Neuroscience letters 5 15265581
2024 EPB41L3 Inhibits the Progression of Cervical Cancer Via the ERK/p38 MAPK Signaling Pathway. Molecular biotechnology 4 38907071
2024 DNA methylation at individual CpG-sites of EPB41L3, HTERT and FAM19A4 are useful for detection of cervical high-grade squamous intraepithelial lesions (HSIL) or worse: Analysis of individual CpG-sites outperforms averaging. Tumour virus research 3 38960143
2024 The MADS-domain transcription factor DAL10 is a direct target of putative DAL1-mediated age pathway in conifers. Journal of experimental botany 3 39082682
2023 Exploring the Diagnostic Potential of EPB41L3 Methylation in Cervical Cancer and Precancerous Lesions: A Systematic Review and Meta-Analysis. Gynecologic and obstetric investigation 3 38081153
2023 Performance of Human Gene EPB41L3 and HPV 16/18 Viral DNA Methylation to Triage hrHPV-Positive Women. Vaccines 3 38250859
2024 Biallelic EPB41L3 variants underlie a developmental disorder with seizures and myelination defects. Brain : a journal of neurology 2 39292993
2019 [Corrigendum] Pivotal roles of protein 4.1B/DAL‑1, a FERM‑domain containing protein, in tumor progression (Review). International journal of oncology 2 31814035

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