Affinage

EPB41

Protein 4.1 · UniProt P11171

Length
864 aa
Mass
97.0 kDa
Annotated
2026-04-28
100 papers in source corpus 45 papers cited in narrative 45 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EPB41 (protein 4.1R) is a FERM-domain scaffold protein that couples transmembrane proteins to the cortical cytoskeleton in erythroid and nonerythroid cells, and additionally functions in mitotic spindle assembly, nuclear envelope organization, and signal transduction. In erythrocytes, its cloverleaf-shaped 30 kDa FERM domain directly binds glycophorin C, band 3, p55, Kell, Duffy, XK, Rh, NHE1, and PMCA1b, anchoring these proteins to the spectrin–actin junctional lattice in a manner regulated by PIP2 (which enhances GPC but inhibits band 3 binding), Ca²⁺/calmodulin (which weakens most interactions), and PKC phosphorylation at Ser312/Ser331 (PMID:11017195, PMID:16669616, PMID:21542582, PMID:18524950). In nonerythroid cells, alternative splicing generates isoforms with nuclear import (exon 16 NLS, importin α/β pathway) or export (exon 5 NES, CRM1 pathway) signals, and 135 kDa isoforms directly bind tubulin, NuMA, and centrosomal components; cdc2-mediated phosphorylation at Thr60/Ser679 targets 4.1R to spindle poles where it is required for bipolar spindle formation, NuMA localization, and asymmetric cell division during erythropoiesis (PMID:10359596, PMID:15525677, PMID:18212055, PMID:34364872). 4.1R also restrains immune cell activation by binding LAT and inhibiting its ZAP-70-mediated phosphorylation in T cells and mast cells, links the E-cadherin/β-catenin complex to actin at adherens junctions via an exon 17b-encoded bispecific domain, and stabilizes nuclear envelope integrity through interactions with emerin and lamin A/C (PMID:19190245, PMID:31776189, PMID:21486941).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 1999 High

    Establishing that 4.1R is essential for erythrocyte membrane skeleton integrity resolved whether 4.1R is a core structural component or merely an accessory factor: 4.1R-null mice showed reduced spectrin and ankyrin, abnormal morphology, and decreased membrane stability.

    Evidence Gene knockout mouse with morphological and protein quantification analysis

    PMID:9927493

    Open questions at the time
    • Precise stoichiometry of 4.1R within the junctional complex unknown
    • Contribution of individual transmembrane binding partners to the KO phenotype not dissected
  2. 1999 High

    Identification of a nonerythroid 4.1R–NuMA interaction and its redistribution to spindle poles established that 4.1R has a mitotic function beyond membrane scaffolding.

    Evidence Yeast two-hybrid, reciprocal co-immunoprecipitation, in vitro binding, and co-localization in dividing cells

    PMID:10189366

    Open questions at the time
    • Whether 4.1R is sufficient for spindle pole focusing not yet tested
    • Regulatory modification controlling mitotic relocalization not identified
  3. 1999 High

    Defining cooperative NLS (exon 16) and acidic EED (exon 5) signals for importin α/β/Ran-dependent nuclear import explained how alternative splicing switches 4.1R between nuclear and cytoplasmic pools.

    Evidence Permeabilized cell import assay, mutagenesis, quantitative binding (KD ~30 nM for importin α2)

    PMID:10359596

    Open questions at the time
    • Functional role of nuclear 4.1R not identified at this stage
    • Splicing regulation of exon 16 not characterized
  4. 2000 High

    The crystal structure of the FERM domain revealed a three-lobed cloverleaf architecture with distinct binding sites for band 3, GPC, and p55, and two calmodulin-binding regions, providing the first structural framework for understanding how 4.1R simultaneously engages multiple membrane proteins.

    Evidence X-ray crystallography with functional binding assays

    PMID:11017195

    Open questions at the time
    • No full-length 4.1R structure available
    • Structural basis for PIP2 regulation not resolved
  5. 2000 High

    Quantitative reconstitution of the GPC–p55–4.1R ternary complex showed that 4.1R enhances p55–GPC affinity ~10-fold and Ca²⁺/calmodulin antagonizes both interactions, establishing Ca²⁺-dependent regulation of the junctional complex.

    Evidence Recombinant truncation constructs with calmodulin competition assays

    PMID:10831591

    Open questions at the time
    • In vivo Ca²⁺ dynamics at the junctional node not measured
    • Whether calmodulin regulation operates during erythropoiesis or in mature red cells unclear
  6. 2000 High

    Discovery that exon 5 encodes a CRM1-dependent nuclear export signal established the molecular basis for cytoplasmic retention of specific 4.1R isoforms, complementing the earlier NLS findings.

    Evidence CRM1/RanGTP-dependent pull-down, mutagenesis of hydrophobic residues, immunofluorescence

    PMID:12427749

    Open questions at the time
    • Physiological stimuli toggling nuclear–cytoplasmic shuttling not defined
  7. 2004 High

    Demonstrating that 4.1R directly binds microtubules and that immunodepletion abolishes aster assembly—rescued by recombinant 4.1R—proved 4.1R is a bona fide microtubule-associated protein required for spindle assembly.

    Evidence Microtubule sedimentation, GST pull-down, immunodepletion/reconstitution of aster assembly in vitro, co-IP from mitotic HeLa extracts

    PMID:15184364 PMID:15525677 PMID:15564380

    Open questions at the time
    • Whether 4.1R stabilizes or nucleates microtubules not distinguished
    • Role of intrinsically disordered C-terminal domain in tubulin binding not structurally resolved
  8. 2004 High

    Identification of cdc2-mediated phosphorylation at Thr60/Ser679 as necessary for spindle pole targeting and enhanced NuMA/tubulin association explained how 4.1R's mitotic role is cell-cycle regulated.

    Evidence In vitro kinase assay, phosphosite mutagenesis, siRNA knockdown with spindle phenotype

    PMID:15525677

    Open questions at the time
    • Phosphatase responsible for dephosphorylation not identified
    • Whether other mitotic kinases contribute not tested
  9. 2005 High

    Showing that PIP2 greatly enhances 4.1R binding to spectrin β-chain CH domains established PIP2 as a regulatory switch for spectrin–actin–4.1R ternary complex assembly at the membrane.

    Evidence Reconstituted ternary complex with recombinant truncation constructs

    PMID:16060676

    Open questions at the time
    • Local PIP2 concentration at junctional nodes in intact erythrocytes not measured
  10. 2006 High

    PIP2 binding to the FERM domain was mapped to K63/64 and K265/266, and shown to differentially modulate partner binding (enhancing GPC, inhibiting band 3), revealing allosteric control of partner selectivity by a single lipid.

    Evidence Liposome binding, site-directed mutagenesis, in vitro protein binding

    PMID:16669616

    Open questions at the time
    • Structural basis for allosteric switch not determined
    • Whether PIP2 and calmodulin regulation are synergistic or antagonistic in vivo unknown
  11. 2006 High

    Identification of Fox-2 (RBFOX2) as the splicing factor that binds UGCAUG and promotes exon 16 inclusion during erythropoiesis connected alternative splicing regulation to the functional domain composition of 4.1R.

    Evidence SELEX, splicing reporter, siRNA knockdown in mouse erythroblasts

    PMID:16537540

    Open questions at the time
    • Upstream signals that regulate RBFOX2 expression during erythropoiesis not addressed
  12. 2008 High

    4.1R knockout erythrocyte proteomics revealed that 4.1R organizes a macromolecular junctional node encompassing GPC, XK, Duffy, and Rh, extending its scaffold role beyond previously known binary interactions.

    Evidence KO mouse, pull-down assays, Western blot, flow cytometry

    PMID:18524950

    Open questions at the time
    • Hierarchy of assembly—whether some partners are bridged indirectly—not established
  13. 2008 High

    RNAi depletion of 4.1R disrupted subdistal appendage proteins (ninein, ODF2), caused G1 arrest and monopolar spindles, extending 4.1R's mitotic role to centrosome maturation and interphase microtubule anchoring.

    Evidence RNA interference, immunofluorescence, cell cycle analysis, live imaging in HeLa cells

    PMID:18212055

    Open questions at the time
    • Direct binding between 4.1R and ninein/ODF2 not demonstrated
    • p53-dependent G1 arrest mechanism not molecularly defined
  14. 2008 High

    4.1R knockout hearts displayed prolonged QT interval, altered Ca²⁺ handling, reduced NaV1.5α, and increased persistent Na⁺ current, revealing a cardiac ion channel scaffolding role.

    Evidence KO mouse, ECG, patch clamp electrophysiology, Ca²⁺ imaging, Western blot

    PMID:18787192

    Open questions at the time
    • Direct binding to NaV1.5 or NCX not demonstrated
    • Whether cardiac phenotype reflects direct scaffolding or secondary effects of membrane instability unclear
  15. 2009 High

    4.1R was shown to negatively regulate T cell activation by binding LAT and blocking ZAP-70-mediated phosphorylation, establishing a direct signaling-inhibitory role beyond structural scaffolding.

    Evidence KO mouse CD4⁺ T cells, co-IP, phosphorylation and cytokine assays

    PMID:19190245

    Open questions at the time
    • Structural basis for LAT–4.1R interaction not resolved
    • Whether 4.1R competes with ZAP-70 for LAT binding or induces conformational masking not distinguished
  16. 2009 High

    Demonstration that 4.1R binds β-catenin and its deficiency disrupts E-cadherin–cytoskeleton linkage and gastric gland architecture established 4.1R as an adherens junction organizer in epithelia.

    Evidence Co-IP, 4.1R KO mouse stomach, biochemical fractionation, histology

    PMID:19376086

    Open questions at the time
    • Domain on 4.1R mediating β-catenin binding not mapped at this stage
  17. 2011 High

    Mapping PKC phosphorylation to Ser312/Ser331 and showing it selectively weakens GPC, Duffy, XK, and β-spectrin binding but not band 3 or Rh binding defined a phosphorylation-based partner-selectivity switch.

    Evidence PKC activation in intact cells, site-specific phosphorylation, detergent extractability

    PMID:21542582

    Open questions at the time
    • In vivo kinetics and stoichiometry of PKC-mediated phosphorylation not measured
    • Phosphatase counteracting this modification unknown
  18. 2011 High

    Co-IP of 4.1R with emerin and lamin A/C, and RNAi-induced nuclear dysmorphology, emerin redistribution, and elevated β-catenin/Wnt signaling, revealed a nuclear envelope integrity function for 4.1R.

    Evidence Co-IP, RNAi, immunofluorescence, β-catenin reporter assay

    PMID:21486941

    Open questions at the time
    • Whether 4.1R is part of the LINC complex not established
    • Mechanism linking nuclear envelope disruption to Wnt activation not defined
  19. 2011 High

    4.1R binding to IQGAP1 and its requirement for IQGAP1 localization to the leading edge established a role in directed cell migration.

    Evidence siRNA, wound-healing assay, co-IP, pull-down, confocal microscopy

    PMID:21750196

    Open questions at the time
    • Domain on 4.1R that binds IQGAP1 not precisely mapped
    • Whether this function involves Rac/Cdc42 signaling not tested
  20. 2011 High

    4.1R deficiency in keratinocytes reduced surface β1-integrin, impairing adhesion, spreading, and wound healing, showing 4.1R links integrins to the cortical cytoskeleton.

    Evidence KO mouse keratinocytes, adhesion/migration assays, flow cytometry, wound model

    PMID:21693581

    Open questions at the time
    • Direct binding interface between 4.1R and β1-integrin not mapped
  21. 2013 High

    4.1R interaction with PMCA1b and KO-induced reduction in enterocyte PMCA1b expression causing impaired calcium absorption and secondary hyperparathyroidism revealed a physiological role in intestinal calcium homeostasis.

    Evidence KO mouse, co-IP, pull-down with recombinant domains, serum Ca²⁺/PTH measurements

    PMID:23460639

    Open questions at the time
    • Whether 4.1R stabilizes PMCA1b at the surface or during trafficking not distinguished
  22. 2013 High

    4.1R interaction with CLASP2 and regulation of cortical microtubule plus-end tethering via local GSK3 activity control extended 4.1R's cytoskeletal roles to interphase microtubule organization.

    Evidence Co-IP, RNAi, live MT dynamics imaging, GSK3 activity assay

    PMID:23943871

    Open questions at the time
    • How 4.1R locally modulates GSK3 activity mechanistically unclear
  23. 2016 High

    Discovery that 4.1R binds VHL and prevents VHL-mediated ubiquitination and degradation of myogenin established a protein stabilization function relevant to muscle differentiation.

    Evidence Co-IP, ubiquitination assay, 4.1R-/- MEFs, knockdown/overexpression rescue

    PMID:27780863

    Open questions at the time
    • Whether 4.1R competes with substrates for VHL binding or alters VHL E3 ligase activity unknown
    • In vivo muscle phenotype in 4.1R KO not fully characterized
  24. 2019 High

    Epithelial 4.1R+17b isoforms were shown to bind β-catenin armadillo repeats 1–2 and link adherens junctions to actin via a bispecific exon 17b-encoded domain, defining the molecular basis for the earlier gastric epithelial phenotype.

    Evidence Co-IP, domain deletion, siRNA depletion with overexpression rescue, calcium-switch AJ reassembly

    PMID:31776189

    Open questions at the time
    • Structure of exon 17b peptide in complex with β-catenin not determined
  25. 2021 High

    4.1R functions within the NuMA–LGN–dynein/dynactin complex to orient the mitotic spindle and enable asymmetric Numb segregation during erythroid differentiation, linking mitotic mechanics to Notch signaling and lineage commitment.

    Evidence siRNA depletion, gene replacement rescue, co-IP, erythroid differentiation assay

    PMID:34364872

    Open questions at the time
    • Whether 4.1R is required for spindle orientation in all cell types or specifically in erythroid progenitors not tested
    • Structural basis for 4.1R integration into the LGN complex unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Full-length 4.1R structure, the interplay between simultaneous post-translational modifications (PIP2, PKC, cdc2, calmodulin) in live cells, and the tissue-specific isoform code that determines which functional modules are active in a given cell type remain unresolved.
  • No full-length structure of any 4.1R isoform
  • Combinatorial regulation by PIP2/PKC/calmodulin/cdc2 not studied in an integrated system
  • Comprehensive tissue-specific isoform expression map with functional annotation lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 7 GO:0005198 structural molecule activity 4 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 2
Localization
GO:0005886 plasma membrane 7 GO:0005856 cytoskeleton 5 GO:0005815 microtubule organizing center 4 GO:0005634 nucleus 3 GO:0005635 nuclear envelope 1
Pathway
R-HSA-1640170 Cell Cycle 5 R-HSA-1500931 Cell-Cell communication 4 R-HSA-162582 Signal Transduction 4 R-HSA-382551 Transport of small molecules 4 R-HSA-168256 Immune System 3
Partners
CTNNB1GYPCIQGAP1LATMPP1NUMA1SLC4A1SPTB
Complex memberships
E-cadherin/beta-catenin adherens junction complexNuMA-LGN-dynein/dynactin complexspectrin-actin junctional complex

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Crystal structure of the 30 kDa N-terminal (FERM) domain of 4.1R reveals a cloverleaf-like architecture with three lobes, each containing specific binding sites for band 3, glycophorin C/D, or p55, and two calmodulin-binding regions at the central junction; Ca2+-dependent calmodulin binding weakens 4.1R interactions with target proteins. X-ray crystallography with functional binding assays Nature structural biology High 11017195
2000 4.1R modulates the GPC-p55 ternary complex: sequences in the 30 kDa domain encoded by exon 8 bind GPC and exon 10 binds p55; 4.1R increases p55-GPC binding affinity ~10-fold; Ca2+/calmodulin binding to 4.1R decreases affinity for both p55 and GPC in a Ca2+-dependent manner. In vitro binding assays with recombinant truncation/deletion constructs, calmodulin competition assays The Journal of biological chemistry High 10831591
2008 4.1R organizes a macromolecular complex at the erythrocyte junctional node including glycophorin C, XK, Duffy, and Rh; deletion of 4.1R in mouse red cells causes loss of actin and extensive cytoskeletal lattice disruption, and pull-down assays confirmed direct association of XK, Duffy, and Rh with 4.1R. 4.1R knockout mouse model, in vitro pull-down assays, Western blot, flow cytometry Proceedings of the National Academy of Sciences of the United States of America High 18524950
1999 A 135 kDa nonerythroid 4.1R isoform specifically interacts with NuMA (nuclear mitotic apparatus protein) via sequences encoded by exons 20-21 of 4.1R and residues 1788-1810 of NuMA; the complex redistributes to spindle poles during mitosis and also includes dynein and dynactin. Yeast two-hybrid, in vitro binding assays, co-immunoprecipitation, coimmunolocalization The Journal of cell biology High 10189366
1999 4.1R-null mice have erythroid membrane skeleton abnormalities including reduced spectrin and ankyrin expression, abnormal morphology, and lowered membrane stability, demonstrating that 4.1R is required for membrane skeleton assembly in erythroid progenitors. Gene knockout mouse model, morphological analysis, protein quantification by SDS-PAGE The Journal of clinical investigation High 9927493
2000 4.1R (135 kDa and 150 kDa isoforms) interacts with tight junction protein ZO-2, co-localizes with ZO-2, ZO-1, and occludin at MDCK tight junctions, and the interaction requires sequences encoded by exons 19-21 of 4.1R and residues 1054-1118 of ZO-2; exogenously expressed 4.1R is recruited to tight junctions in confluent cells. Yeast two-hybrid, immunocolocalization, co-immunoprecipitation, in vitro binding assays, domain mapping The Journal of biological chemistry High 10874042
1999 Nuclear import of 4.1R80 requires two co-operative signals: a basic NLS (KKKRER) encoded by alternative exon 16 and an acidic EED motif encoded by exon 5; 4.1R80 is imported via the importin alpha2 (Rch1)/importin beta/Ran pathway with KD ~30 nM for Rch1. Transfection of mutagenized constructs, permeabilized cell import assay, resonant mirror detection binding, fusion to cytoplasmic reporter Molecular biology of the cell High 10359596
2006 4.1R binds PIP2 through its 30 kDa membrane-binding domain; PIP2 binding induces a conformational change and differentially regulates 4.1R interactions: enhancing binding to glycophorin C, inhibiting binding to band 3, with no effect on p55 binding; residues K63,64 and K265,266 are required for PIP2 interaction. Liposome binding assays, site-directed mutagenesis, in vitro protein binding assays, Triton X-100 extraction from intact cells Biochemistry High 16669616
2005 4.1R binds to the N-terminal spectrin beta chain region (residues 1-301) containing CH1 and CH2 calponin homology domains; PIP2 greatly enhances 4.1R binding to spectrin, suggesting a regulatory switch; the CH1 but not intact CH2 domain binds F-actin. In vitro binding assays with recombinant truncation constructs, ternary complex reconstitution Biochemistry High 16060676
2011 PKC-mediated phosphorylation of 4.1R at serine 312 and serine 331 weakens its interactions with GPC, Duffy, XK, and β-spectrin but does not affect band 3 or Rh binding, demonstrating that phosphorylation of a regulatory domain structurally modulates the functional interaction centers of 4.1R. Phosphorylation in intact cells with PKC activation, in solution phosphorylation, detergent extractability assay, competitive peptide assay Biochemistry High 21542582
2001 4.1R binding to phosphatidylserine involves initial interaction of YKRS residues with the serine head group followed by tight hydrophobic interaction with acyl chains; association of acyl chains with 4.1R impairs its binding to calmodulin, band 3, and glycophorin C; this interaction may play a role in cellular sorting of 4.1R. Liposome binding assays, phospholipase treatment, ionic strength extraction, in vitro binding competition assays The Journal of biological chemistry High 11423550
2004 Mitotic phosphorylation of 4.1R by p34cdc2 kinase at Thr60 and Ser679 is required for targeting of 4.1R to spindle poles and for mitotic microtubule aster assembly in vitro; phosphorylation enhances association with NuMA and tubulin; siRNA depletion of 4.1R impairs bipolar spindle pole focusing. In vitro kinase assay, site-directed mutagenesis, immunodepletion/reconstitution of aster assembly, siRNA knockdown, co-immunoprecipitation Molecular biology of the cell High 15525677
2004 4.1R directly associates with microtubules through both its membrane-binding and C-terminal domains; immunodepletion of 4.1R from mitotic extract abolishes aster assembly; addition of recombinant 135 kDa 4.1R reconstitutes asters; in vivo 4.1R forms a complex with tubulin and NuMA in mitotic HeLa extracts. In vitro sedimentation assays, GST pull-down, immunodepletion/reconstitution of aster assembly, co-immunoprecipitation from synchronized mitotic cells The Journal of biological chemistry High 15184364
2008 4.1R depletion by RNAi disrupts subdistal appendage proteins ninein and ODF2/cenexin at mature centrioles, reduces interphase microtubule anchoring, causes G1 arrest in p53-proficient cells, leads to monopolar spindle formation, and produces mislocalized NuMA at defective spindles with lagging chromosomes in anaphase. RNA interference, immunofluorescence, cell cycle analysis, live imaging Molecular and cellular biology High 18212055
2001 A constitutive domain of 4.1R containing heptad leucine repeats directly binds tubulin; 4.1R co-sediments with taxol-polymerized microtubules; ectopic expression of 4.1R causes microtubule disorganization in COS-7 cells. Microtubule sedimentation assay, GST pull-down, confocal co-localization, in vitro binding assays The Journal of biological chemistry High 11579097
2004 4.1R is present in isolated centrosome preparations and promotes microtubule aster assembly in vitro; 4.1R-transfected cells show disrupted microtubule organization at centrosomes with altered distribution of p150Glued and dynein intermediate chain, while gamma-tubulin and pericentrin remain. Centrosome isolation, in vitro microtubule aster-assembly assay, confocal microscopy, microtubule depolymerization-repolymerization assay Journal of cell science High 15564380
2009 4.1R directly interacts with beta-catenin; in 4.1R-deficient stomach epithelia, beta-catenin is selectively reduced, E-cadherin linkage to the cytoskeleton is weakened, actin organization is altered, and gastric gland structure is disorganized. Co-immunoprecipitation, 4.1R knockout mouse model, biochemical fractionation, histology Biochimica et biophysica acta High 19376086
2009 4.1R negatively regulates T cell activation by binding directly to LAT (linker for activation of T cells) and inhibiting its phosphorylation by ZAP-70; 4.1R-deficient CD4+ T cells show hyperactivation with enhanced LAT and ERK phosphorylation, hyperproliferation, and increased IL-2 and IFN-gamma production. 4.1R knockout mouse, direct binding assay (Co-IP), phosphorylation analysis, proliferation and cytokine assays Blood High 19190245
2011 4.1R co-immunoprecipitates with emerin and lamin A/C; 4.1R depletion causes nuclear dysmorphology, redistribution of emerin into cytoplasm, disorganization of lamin A/C, increased nucleus-centrosome distances, increased nuclear beta-catenin/Wnt signaling, and mislocalization of multiple nuclear envelope proteins. Co-immunoprecipitation, RNAi knockdown, immunofluorescence, beta-catenin signaling reporter assays Journal of cell science High 21486941
2008 4.1R knockout mice show prolonged QT interval, prolonged action potential duration, larger and slower Ca2+ transients, reduced NCX current density, increased persistent Na+ current, and reduced NaV1.5alpha expression, indicating that 4.1R modulates cardiac ion transporter function. 4.1R knockout mouse, ECG, patch clamp electrophysiology, Ca2+ imaging, Western blot Circulation research High 18787192
2013 4.1R directly associates with plasma membrane calcium ATPase PMCA1b via the 4.1R membrane-binding domain and the second intracellular loop/C-terminus of PMCA1b; 4.1R knockout mice have reduced PMCA1b expression in enterocytes and impaired intestinal calcium absorption with secondary hyperparathyroidism. 4.1R knockout mouse, co-localization, co-immunoprecipitation, in vitro pull-down with recombinant domain constructs, serum calcium/PTH/vitamin D measurements The Journal of biological chemistry High 23460639
2000 4.1R binds eIF3-p44 (a subunit of eukaryotic translation initiation factor 3) via the 4.1R C-terminal 22/24 kDa domain (residues 525-622) interacting with eIF3-p44 residues 54-321; depletion of eIF3-p44 from reticulocyte lysates abolishes translation. Yeast two-hybrid, in vitro binding assays, co-immunoprecipitation, cell-free translation depletion assay Blood High 10887144
2000 4.1R isoforms in skeletal muscle (~105/110 kDa) co-purify with myosin, alpha-actin, and alpha-tropomyosin in a supramolecular complex; in vitro binding assays show 4.1R interacts directly with these contractile proteins through its 10 kDa domain. Co-immunoprecipitation from muscle homogenates, in vitro binding assays, immunolocalization Molecular biology of the cell Medium 11071908
2011 4.1R is required for cell migration persistence and directionality; 4.1R binds scaffold protein IQGAP1 via its membrane-binding domain and is required for localization of IQGAP1 to the leading edge of migrating cells. siRNA knockdown, wound-healing assay, co-immunoprecipitation, pull-down assays, confocal microscopy Journal of cell science High 21750196
2011 4.1R deficiency in keratinocytes reduces surface expression and activity of beta1 integrin, impairing cell adhesion, spreading, migration, actin stress fiber/focal adhesion formation, and wound healing in 4.1R-/- mice; direct association between 4.1R and beta1 integrin was identified. 4.1R knockout mouse, cell adhesion/spreading/migration assays, flow cytometry for surface beta1 integrin, wound-healing model Journal of cell science High 21693581
2013 4.1R interacts and co-localizes with cortical CLASP2 and controls CLASP2 cortical platform number and dynamics; 4.1R knockdown causes loss of MT plus-end tethering to the cell cortex by locally altering GSK3 activity, disrupting radial microtubule organization. Co-immunoprecipitation, RNAi knockdown, live imaging of MT dynamics, GSK3 activity assay Journal of cell science High 23943871
2016 4.1R associates with VHL protein and prevents VHL-mediated ubiquitination and proteasomal degradation of myogenin; 4.1R depletion reduces myogenin protein (but not mRNA) levels and impairs skeletal muscle differentiation, with decreased myosin heavy/light chains and caveolin-3. Co-immunoprecipitation, ubiquitination assay, 4.1R-/- MEF cells, knockdown, overexpression rescue The Journal of biological chemistry High 27780863
2021 4.1R functions as a member of the NuMA-LGN-dynein/dynactin complex to regulate mitotic spindle orientation; 4.1R-NuMA interaction is required for asymmetric segregation of Numb during erythroid differentiation; disruption of the complex increases Notch signaling and reduces erythroblast population. siRNA depletion, gene replacement, co-immunoprecipitation, immunofluorescence, erythroid differentiation assay The Journal of biological chemistry High 34364872
2006 Fox-2 (RBFOX2) binds the intronic UGCAUG element downstream of 4.1R exon 16 and promotes exon 16 inclusion during erythropoiesis; knockdown of Fox-2 decreases exon 16 splicing; this constitutes positive regulation of the spectrin/actin-binding domain inclusion switch. SELEX, co-transfection splicing assay, siRNA knockdown, immunoblot in mouse erythroblasts The Journal of biological chemistry High 16537540
2011 RBFOX2 promotes 4.1R exon 16 5' splice site usage by recruiting U1 snRNP through direct interaction of RBFOX2's C-terminal domain with the zinc finger region of U1C protein, thereby stabilizing the pre-mRNA/U1 snRNP complex at a weak 5' splice site. Mutagenesis of splice sites, siRNA knockdown, direct protein-protein interaction assay (RBFOX2 CTD with U1C), splicing reporter assay Molecular and cellular biology High 22083953
2000 Exon 5 of 4.1R encodes a leucine-rich nuclear export signal (NES) that binds the export receptor CRM1 in a RanGTP-dependent manner; two conserved hydrophobic residues are essential for CRM1 binding and for cytoplasmic localization of 4.1R isoforms containing exon 5. CRM1 binding assay, RanGTP-dependent pull-down, site-directed mutagenesis, immunofluorescence localization The Journal of biological chemistry High 12427749
2012 4.1R directly binds the cytoplasmic domain of NHE1 (Na+/H+ exchanger 1) via an EED motif in the 4.1R FERM domain interacting with basic residue clusters K519R and R556FNKKYVKK in NHE1; the interaction has KD ~100-200 nM and is reduced by Ca2+/calmodulin binding to 4.1R and by acidic/hypertonic conditions. In vitro binding assays, resonant mirror detection (quantitative KD), calmodulin competition assay The Biochemical journal High 22731252
2010 NMR characterization of the 4.1R C-terminal domain shows it behaves as an intrinsically disordered protein with a central helical region; the N-terminal and central helical regions mediate interaction with NuMA1; phosphorylation of the NuMA1 interacting peptide shifts the interaction to involve the central helical and C-terminal regions of 4.1R, suggesting phosphorylation-dependent regulation of the 4.1R-NuMA1 complex. NMR spectroscopy, NMR titration mapping of interaction interface BMC biochemistry Medium 20109190
2008 4.1R isoforms expressed in erythroid cells contain an alternatively spliced exon 5 that encodes a second p55-binding site in the FERM domain; the exon 5 peptide binds to a site on p55 D5 domain independent of the exon 10 site; exon 5 inclusion is required for membrane targeting of the 135 kDa 4.1R isoform in epithelial cells. Surface Plasmon Resonance (quantitative binding), competition assays, transfection with deletion constructs, immunofluorescence localization Biochimica et biophysica acta High 18952129
2015 Kell blood group protein directly interacts with 4.1R; pull-down and co-immunoprecipitation from erythrocyte membranes demonstrate the interaction; the R46R juxta-membrane motif of Kell binds to lobe B of the 4.1R FERM domain; 4.1R deficiency is associated with reduced Kell, XK, DARC, and urea transporter B expression. In vitro pull-down with recombinant domain constructs, co-immunoprecipitation, flow cytometry, Western blot British journal of haematology High 26455906
2019 4.1R negatively regulates CD8+ T cell activation by binding directly to LAT and inhibiting LAT phosphorylation; 4.1R-/- CD8+ T cells show enhanced LAT and ERK phosphorylation, increased proliferation, and elevated IL-2 and IFN-gamma secretion. 4.1R knockout mouse, co-immunoprecipitation, phosphorylation analysis Immunology High 31135971
2019 4.1R directly binds EGFR via co-immunoprecipitation in keratinocytes; 4.1R knockout augments EGFR expression, phosphorylation, and downstream Akt/ERK signaling, causing keratinocyte hyperproliferation; EGFR or MEK inhibitors rescue the hyperproliferation phenotype. 4.1R knockout mouse/cells, co-immunoprecipitation, immunofluorescence, pharmacological inhibitors, proliferation assays Experimental cell research Medium 31562860
2020 EPB41 protein directly interacts with ALDOC; EPB41 loss releases free ALDOC, which disrupts the beta-catenin destruction complex, leading to reduced GSK3beta activity, beta-catenin accumulation, and nuclear translocation, thereby activating Wnt target oncogenes in NSCLC. Co-immunoprecipitation, beta-catenin stability assay, nuclear/cytoplasmic fractionation, cell proliferation/invasion assays, mouse xenograft Cancer letters Medium 33242559
2019 Epithelial-specific 4.1R isoforms containing exon 17b (4.1R+17b) bind armadillo repeats 1-2 of beta-catenin via the membrane-binding domain and link AJs to the actin cytoskeleton through an exon 17b-encoded bispecific actin interaction; depletion of 4.1R+17b reduces junctional actin, spectrin, and E-cadherin during AJ reassembly. Co-immunoprecipitation, siRNA depletion, overexpression rescue, calcium-switch AJ reassembly assay, immunofluorescence The Journal of biological chemistry High 31776189
2009 4.1R isoforms translated from ATG-1 (135 kDa) localize to plasma membrane/ER and are excluded from the nucleus; the 209 aa N-terminal headpiece domain confers this non-nuclear localization and inhibits nuclear targeting of otherwise nuclear ATG-2-translated isoforms. Transfection of tagged isoforms, immunofluorescence, subcellular fractionation, domain fusion experiments Proceedings of the National Academy of Sciences of the United States of America High 10611314
2009 4.1R-null erythrocytes have elevated Na/H exchange activity with increased Vmax and altered osmolality sensitivity; okadaic acid activation of Na/H exchange is absent in 4.1R-null cells, suggesting 4.1R normally downregulates NHE activity through a phosphorylation-dependent mechanism. 4.1R knockout mouse, flux assays for ion transport, pharmacological dissection with specific inhibitors American journal of physiology. Cell physiology Medium 16774987
2024 4.1R directly interacts with TLR4 and inhibits the AKT/HIF-1alpha signaling pathway; 4.1R deficiency enhances glycolytic metabolism via PKM2 upregulation, promoting M1 macrophage polarization and sepsis-induced liver injury. Co-immunoprecipitation (4.1R-TLR4), 4.1R knockout model, glycolysis assays, Western blot for AKT/HIF-1alpha/PKM2 International immunopharmacology Medium 38237224
2020 In mast cells, 4.1R co-immunoprecipitates with LAT1 and LAT2; 4.1R knockout reduces antigen-induced phosphorylation of SYK and downstream signaling (LAT1, PLCgamma1, SHP1, SHIP, MAPKs, STAT5), impairs degranulation and calcium response, without affecting FcεRI beta/gamma subunit phosphorylation. 4.1R knockout mouse, co-immunoprecipitation, phosphorylation analysis, degranulation assay, calcium imaging, in vivo passive cutaneous anaphylaxis Frontiers in immunology High 31993060
2002 4.1R C-terminal domain (exons 20-21) associates with spindle poles; a splice mutation (CO.2) lacking exon 20-encoded sequence but retaining exon 21 co-localizes with NuMA at spindle poles, whereas CO.1 lacking exon 21 does not; intact C-terminal end is required for stable centrosome association. Expression of patient-derived splice variants, immunofluorescence co-localization with NuMA, microtubule-destabilizing conditions Blood Medium 12239178
2011 Apo-calmodulin binding stabilizes the beta-strand-rich C-lobe of the 4.1R 30 kDa FERM domain (R30) against thermal denaturation; Ca2+-independent CaM binding maintains p55 binding at elevated temperatures; CaM binding does not aggregate R30 but alters its secondary structure dynamics. Resonant mirror detection (KD at multiple temperatures), FTIR spectroscopy, dynamic light scattering The Biochemical journal Medium 21848512

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Protein 4.1R-dependent multiprotein complex: new insights into the structural organization of the red blood cell membrane. Proceedings of the National Academy of Sciences of the United States of America 198 18524950
2015 Optimization of a Novel Binding Motif to (E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic Acid (AZD9496), a Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist. Journal of medicinal chemistry 137 26407012
2004 Hereditary elliptocytosis: spectrin and protein 4.1R. Seminars in hematology 127 15071791
2000 Characterization of the interaction between protein 4.1R and ZO-2. A possible link between the tight junction and the actin cytoskeleton. The Journal of biological chemistry 124 10874042
1999 A nonerythroid isoform of protein 4.1R interacts with the nuclear mitotic apparatus (NuMA) protein. The Journal of cell biology 111 10189366
2000 Protein 4.1R core domain structure and insights into regulation of cytoskeletal organization. Nature structural biology 104 11017195
1999 Protein 4.1R-deficient mice are viable but have erythroid membrane skeleton abnormalities. The Journal of clinical investigation 102 9927493
2006 Fox-2 splicing factor binds to a conserved intron motif to promote inclusion of protein 4.1R alternative exon 16. The Journal of biological chemistry 100 16537540
1998 Cloning and characterization of 4.1G (EPB41L2), a new member of the skeletal protein 4.1 (EPB41) gene family. Genomics 97 9598318
2000 Regulation of protein 4.1R, p55, and glycophorin C ternary complex in human erythrocyte membrane. The Journal of biological chemistry 84 10831591
2018 EL1-like Casein Kinases Suppress ABA Signaling and Responses by Phosphorylating and Destabilizing the ABA Receptors PYR/PYLs in Arabidopsis. Molecular plant 79 29505832
2015 Identification of N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide (PIM447), a Potent and Selective Proviral Insertion Site of Moloney Murine Leukemia (PIM) 1, 2, and 3 Kinase Inhibitor in Clinical Trials for Hematological Malignancies. Journal of medicinal chemistry 67 26505898
2003 Identification of a third Protein 4.1 tumor suppressor, Protein 4.1R, in meningioma pathogenesis. Neurobiology of disease 66 12901833
1998 Characterization of multiple isoforms of protein 4.1R expressed during erythroid terminal differentiation. Blood 63 9834247
2005 Identification and functional characterization of protein 4.1R and actin-binding sites in erythrocyte beta spectrin: regulation of the interactions by phosphatidylinositol-4,5-bisphosphate. Biochemistry 61 16060676
2001 Multiple cis elements regulate an alternative splicing event at 4.1R pre-mRNA during erythroid differentiation. Blood 55 11739190
2006 Phosphatidylinositol-4,5-biphosphate (PIP2) differentially regulates the interaction of human erythrocyte protein 4.1 (4.1R) with membrane proteins. Biochemistry 49 16669616
2009 Protein 4.1R links E-cadherin/beta-catenin complex to the cytoskeleton through its direct interaction with beta-catenin and modulates adherens junction integrity. Biochimica et biophysica acta 46 19376086
2008 Cytoskeletal protein 4.1R affects repolarization and regulates calcium handling in the heart. Circulation research 45 18787192
2013 Draft Genome Sequence of the Grapevine Dieback Fungus Eutypa lata UCR-EL1. Genome announcements 43 23723393
2001 Structural and functional characterization of protein 4.1R-phosphatidylserine interaction: potential role in 4.1R sorting within cells. The Journal of biological chemistry 43 11423550
2006 Regulation of protein 4.1R interactions with membrane proteins by Ca2+ and calmodulin. Frontiers in bioscience : a journal and virtual library 41 16368534
2010 Identification of SNP markers on 1p36 and association analysis of EPB41 with mandibular prognathism in a Chinese population. Archives of oral biology 40 20797695
1999 Deciphering the nuclear import pathway for the cytoskeletal red cell protein 4.1R. Molecular biology of the cell 40 10359596
2000 A nonerythroid isoform of protein 4.1R interacts with components of the contractile apparatus in skeletal myofibers. Molecular biology of the cell 39 11071908
2011 Phosphorylation-dependent perturbations of the 4.1R-associated multiprotein complex of the erythrocyte membrane. Biochemistry 38 21542582
2007 Regulated Fox-2 isoform expression mediates protein 4.1R splicing during erythroid differentiation. Blood 38 17715393
2009 Cytoskeletal protein 4.1R negatively regulates T-cell activation by inhibiting the phosphorylation of LAT. Blood 37 19190245
2011 Protein 4.1R regulates cell adhesion, spreading, migration and motility of mouse keratinocytes by modulating surface expression of beta1 integrin. Journal of cell science 35 21693581
2011 RBFOX2 promotes protein 4.1R exon 16 selection via U1 snRNP recruitment. Molecular and cellular biology 35 22083953
2005 GADD45A and EPB41 as tumor suppressor genes in meningioma pathogenesis. Cancer genetics and cytogenetics 35 16157202
2004 Differential domain evolution and complex RNA processing in a family of paralogous EPB41 (protein 4.1) genes facilitate expression of diverse tissue-specific isoforms. Genomics 32 15475241
2016 2-Chloro-4-[[(1R,2R)-2-hydroxy-2-methyl-cyclopentyl]amino]-3-methyl-benzonitrile: A Transdermal Selective Androgen Receptor Modulator (SARM) for Muscle Atrophy. Journal of medicinal chemistry 31 26683992
2016 Integrative Functional Genomics Implicates EPB41 Dysregulation in Hepatocellular Carcinoma Risk. American journal of human genetics 31 27453575
2001 Protein 4.1 in forebrain postsynaptic density preparations: enrichment of 4.1 gene products and detection of 4.1R binding proteins. European journal of biochemistry 31 11179975
2011 Protein 4.1R regulates cell migration and IQGAP1 recruitment to the leading edge. Journal of cell science 29 21750196
2003 Alternative 5' exons and differential splicing regulate expression of protein 4.1R isoforms with distinct N-termini. Blood 29 12522012
2000 A constitutive region is responsible for nuclear targeting of 4.1R: modulation by alternative sequences results in differential intracellular localization. Journal of cell science 29 10852827
2004 An erythroid differentiation-specific splicing switch in protein 4.1R mediated by the interaction of SF2/ASF with an exonic splicing enhancer. Blood 28 15522963
2000 Protein 4.1R binding to eIF3-p44 suggests an interaction between the cytoskeletal network and the translation apparatus. Blood 28 10887144
2013 Impaired intestinal calcium absorption in protein 4.1R-deficient mice due to altered expression of plasma membrane calcium ATPase 1b (PMCA1b). The Journal of biological chemistry 27 23460639
2011 Structural protein 4.1R is integrally involved in nuclear envelope protein localization, centrosome-nucleus association and transcriptional signaling. Journal of cell science 27 21486941
2007 Intrasplicing coordinates alternative first exons with alternative splicing in the protein 4.1R gene. The EMBO journal 27 18079699
2020 EPB41 suppresses the Wnt/β-catenin signaling in non-small cell lung cancer by sponging ALDOC. Cancer letters 26 33242559
2008 Downregulation of protein 4.1R, a mature centriole protein, disrupts centrosomes, alters cell cycle progression, and perturbs mitotic spindles and anaphase. Molecular and cellular biology 26 18212055
2001 4.1R proteins associate with interphase microtubules in human T cells: a 4.1R constitutive region is involved in tubulin binding. The Journal of biological chemistry 25 11579097
2006 Effect of complete protein 4.1R deficiency on ion transport properties of murine erythrocytes. American journal of physiology. Cell physiology 24 16774987
2009 Marked difference in membrane-protein-binding properties of the two isoforms of protein 4.1R expressed at early and late stages of erythroid differentiation. The Biochemical journal 23 18691159
2017 Protein 4.1R Exon 16 3' Splice Site Activation Requires Coordination among TIA1, Pcbp1, and RBM39 during Terminal Erythropoiesis. Molecular and cellular biology 22 28193846
2021 Suppression of 4.1R enhances the potency of NKG2D-CAR T cells against pancreatic carcinoma via activating ERK signaling pathway. Oncogenesis 21 34548478
2004 Protein 4.1R, a microtubule-associated protein involved in microtubule aster assembly in mammalian mitotic extract. The Journal of biological chemistry 20 15184364
2004 Protein 4.1R regulates interphase microtubule organization at the centrosome. Journal of cell science 20 15564380
2000 Alternative splicing of protein 4.1R exon 16: ordered excision of flanking introns ensures proper splice site choice. Blood 20 10627481
1999 The N-terminal 209-aa domain of high molecular-weight 4.1R isoforms abrogates 4.1R targeting to the nucleus. Proceedings of the National Academy of Sciences of the United States of America 19 10611314
2008 Rational design and synthesis of 4-((1R,2R)-2-hydroxycyclohexyl)-2(trifluoromethyl)benzonitrile (PF-998425), a novel, nonsteroidal androgen receptor antagonist devoid of phototoxicity for dermatological indications. Journal of medicinal chemistry 18 18921992
2008 Alternatively spliced exon 5 of the FERM domain of protein 4.1R encodes a novel binding site for erythrocyte p55 and is critical for membrane targeting in epithelial cells. Biochimica et biophysica acta 18 18952129
2003 Low expression of MDS1-EVI1-like-1 (MEL1) and EVI1-like-1 (EL1) genes in favorable-risk acute myeloid leukemia. Experimental hematology 17 14585371
2002 An alternative domain containing a leucine-rich sequence regulates nuclear cytoplasmic localization of protein 4.1R. The Journal of biological chemistry 17 12427749
1991 Rapid localization of membrane skeletal protein 4.1 (EL1) to human chromosome 1p33----p34.2 by nonradioactive in situ hybridization. Cytogenetics and cell genetics 17 1914519
2013 Protein 4.1R binds to CLASP2 and regulates dynamics, organization and attachment of microtubules to the cell cortex. Journal of cell science 16 23943871
2012 Characterization of cytoskeletal protein 4.1R interaction with NHE1 (Na(+)/H(+) exchanger isoform 1). The Biochemical journal 16 22731252
2008 Association between myeloid malignancies and acquired deficit in protein 4.1R: a retrospective analysis of six patients. American journal of hematology 16 17994571
2002 A splicing alteration of 4.1R pre-mRNA generates 2 protein isoforms with distinct assembly to spindle poles in mitotic cells. Blood 16 12239178
2011 Structural stabilization of protein 4.1R FERM domain upon binding to apo-calmodulin: novel insights into the biological significance of the calcium-independent binding of calmodulin to protein 4.1R. The Biochemical journal 15 21848512
2009 4.1R-deficient human red blood cells have altered phosphatidylserine exposure pathways and are deficient in CD44 and CD47 glycoproteins. Haematologica 15 19794081
2004 Mitotic regulation of protein 4.1R involves phosphorylation by cdc2 kinase. Molecular biology of the cell 15 15525677
2015 The human Kell blood group binds the erythroid 4.1R protein: new insights into the 4.1R-dependent red cell membrane complex. British journal of haematology 14 26455906
2011 Rice homeobox transcription factor HOX1a positively regulates gibberellin responses by directly suppressing EL1. Journal of integrative plant biology 14 21951842
1995 Isolation and Purification of Enterocin EL1, a Bacteriocin Produced by a Strain of Enterococcus faecium †. Journal of food protection 14 31137390
2022 Circular RNA EPB41 expression predicts unfavorable prognoses in NSCLC by regulating miR-486-3p/eIF5A axis-mediated stemness. Cancer cell international 13 35725615
2012 Isoforms of protein 4.1 are differentially distributed in heart muscle cells: relation of 4.1R and 4.1G to components of the Ca2+ homeostasis system. Experimental cell research 13 22429617
2009 Coupled transcription-splicing regulation of mutually exclusive splicing events at the 5' exons of protein 4.1R gene. Blood 13 19729518
2011 Insights into the Function of the Unstructured N-Terminal Domain of Proteins 4.1R and 4.1G in Erythropoiesis. International journal of cell biology 12 21904552
2007 Characterization of protein 4.1R in erythrocytes of zebrafish (Danio rerio): unique binding properties with transmembrane proteins and calmodulin. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 12 17569566
2004 Spi-1/PU.1 but not Fli-1 inhibits erythroid-specific alternative splicing of 4.1R pre-mRNA in murine erythroleukemia cells. Oncogene 12 14647452
2020 CADM1 promotes malignant features of small-cell lung cancer by recruiting 4.1R to the plasma membrane. Biochemical and biophysical research communications 11 33298314
2017 Circulating primitive erythroblasts establish a functional, protein 4.1R-dependent cytoskeletal network prior to enucleating. Scientific reports 11 28701737
2011 Homozygous deletion of EPB41 genuine AUG-containing exons results in mRNA splicing defects, NMD activation and protein 4.1R complete deficiency in hereditary elliptocytosis. Blood cells, molecules & diseases 11 21839655
2005 Evolutionarily conserved coupling of transcription and alternative splicing in the EPB41 (protein 4.1R) and EPB41L3 (protein 4.1B) genes. Genomics 11 16242908
2020 Cytoskeletal Protein 4.1R Is a Positive Regulator of the FcεRI Signaling and Chemotaxis in Mast Cells. Frontiers in immunology 10 31993060
2014 Inhibition of human pyridoxal kinase by 2-acetyl-4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)imidazole (THI). Journal of enzyme inhibition and medicinal chemistry 9 24899377
2020 Cytoskeleton protein 4.1R regulates B-cell fate by modulating the canonical NF-κB pathway. Immunology 8 32852059
2016 Protein 4.1R Influences Myogenin Protein Stability and Skeletal Muscle Differentiation. The Journal of biological chemistry 8 27780863
2024 Protein 4.1R regulates M1 macrophages polarization via glycolysis, alleviating sepsis-induced liver injury in mice. International immunopharmacology 7 38237224
2021 The protein 4.1R downregulates VEGFA in M2 macrophages to inhibit colon cancer metastasis. Experimental cell research 7 34717920
2020 Protein 4.1R affects photodynamic therapy for B16 melanoma by regulating the transport of 5-aminolevulinic acid. Experimental cell research 7 33385415
2019 Protein 4.1R negatively regulates CD8+ T-cell activation by modulating phosphorylation of linker for activation of T cells. Immunology 7 31135971
2019 Cytoskeleton protein 4.1R suppresses murine keratinocyte cell hyperproliferation via activating the Akt/ERK pathway in an EGFR-dependent manner. Experimental cell research 7 31562860
2010 Nonsense-mediated mRNA decay (NMD) blockage promotes nonsense mRNA stabilization in protein 4.1R deficient cells carrying the 4.1R Coimbra variant of hereditary elliptocytosis. Blood cells, molecules & diseases 7 20863723
2016 Alternative polyadenylation in a family of paralogous EPB41 genes generates protein 4.1 diversity. RNA biology 6 27981895
2014 Protein 4.1R attenuates autoreactivity in experimental autoimmune encephalomyelitis by suppressing CD4(+) T cell activation. Cellular immunology 6 25243644
2008 CYP2C75-involved autoinduction of metabolism in rhesus monkeys of methyl 3-chloro-3'-fluoro-4'-{(1R)-1-[({1-[(trifluoroacetyl)amino]cyclopropyl}carbonyl)amino]ethyl}-1,1'-biphenyl-2-carboxylate (MK-0686), a bradykinin B1 receptor antagonist. The Journal of pharmacology and experimental therapeutics 6 18310472
2022 Are EPB41 and alpha-synuclein diagnostic biomarkers of sport-related concussion? Findings from the NCAA and Department of Defense CARE Consortium. Journal of sport and health science 5 36403906
2021 Multifunctional protein 4.1R regulates the asymmetric segregation of Numb during terminal erythroid maturation. The Journal of biological chemistry 5 34364872
2019 Epithelial-specific isoforms of protein 4.1R promote adherens junction assembly in maturing epithelia. The Journal of biological chemistry 5 31776189
2018 Lnc-EPB41-Protein Interactions Associated with Congenital Pouch Colon. Biomolecules 5 30227690
2014 ICln: a new regulator of non-erythroid 4.1R localisation and function. PloS one 5 25295618
2013 Combined inhibition of PI3K and activation of MAPK p38 signaling pathways trigger erythroid alternative splicing switch of 4.1R pre-mRNA in DMSO-induced erythroleukemia cells. Cellular signalling 5 23993958
2010 NMR characterisation of the minimal interacting regions of centrosomal proteins 4.1R and NuMA1: effect of phosphorylation. BMC biochemistry 5 20109190
2007 Neuroacanthocytosis associated with a defect of the 4.1R membrane protein. BMC neurology 5 17298666