Affinage

EPB41

Protein 4.1 · UniProt P11171

Length
864 aa
Mass
97.0 kDa
Annotated
2026-06-09
100 papers in source corpus 48 papers cited in narrative 48 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Protein 4.1R (EPB41) is a multifunctional cytoskeletal adaptor that links integral membrane proteins to the spectrin–actin network, with its cloverleaf-shaped N-terminal FERM (30 kDa) domain providing three distinct lobes that engage band 3, glycophorin C/D, and the membrane palmitoylated protein p55 (PMID:11017195). Within this domain, exon 8-encoded sequences form the glycophorin C interface and exon 10-encoded sequences the p55 interface, and 4.1R increases p55–glycophorin C affinity by an order of magnitude, nucleating a ternary spectrin–F-actin junctional complex whose loss in knockout erythrocytes causes hemolytic anemia, membrane instability, and reduced spectrin/ankyrin (PMID:10831591, PMID:16060676, PMID:9927493). This adaptor function organizes a macromolecular junctional complex that retains multiple transmembrane proteins—glycophorin C, XK, Duffy, Rh, and Kell—at the red cell membrane (PMID:18524950, PMID:26455906). These interactions are dynamically gated: Ca2+/calmodulin binding weakens 4.1R–target affinity (PMID:11017195, PMID:10831591), PIP2 binding induces a conformational change that selectively enhances glycophorin C binding while inhibiting band 3 binding (PMID:16669616), phosphatidylserine acyl-chain engagement impairs binding to calmodulin, band 3, and glycophorin C (PMID:11423550), and PKC phosphorylation at Ser312/Ser331 suppresses binding to membrane proteins and β-spectrin to destabilize the junction (PMID:21542582). Beyond the erythrocyte, nonerythroid high-molecular-weight isoforms (135 kDa) directly bind microtubules and tubulin and are essential for organizing mitotic asters: immunodepletion disperses microtubules and recombinant 4.1R restores asters (PMID:15184364, PMID:11579097). cdc2-dependent phosphorylation at Thr60/Ser679 targets 4.1R to spindle poles and enhances its association with NuMA and tubulin, where it acts within a NuMA–LGN–dynein/dynactin complex to focus spindle poles, regulate spindle orientation, and direct asymmetric Numb segregation during erythroid differentiation (PMID:10189366, PMID:15525677, PMID:34364872); it also localizes to centrosome subdistal appendages to anchor interphase microtubules (PMID:18212055). 4.1R maintains nuclear architecture through interactions with emerin and lamin A/C (PMID:21486941) and supports epithelial integrity at adherens junctions by directly binding β-catenin, an exon 17b-dependent linkage that promotes fodrin–actin assembly (PMID:19376086, PMID:31776189), and at tight junctions by binding ZO-2 (PMID:10874042). Nuclear access of 4.1R is controlled by alternative splicing: exon 16 encodes a core NLS and exon 5 encodes a CRM1-dependent nuclear export signal, with their combination determining nucleocytoplasmic distribution (PMID:10359596, PMID:12427749). In immune cells, 4.1R is recruited to the immunological synapse and negatively regulates lymphocyte activation by directly binding LAT and inhibiting its ZAP-70-mediated phosphorylation, dampening downstream ERK signaling and cytokine output in CD4+ and CD8+ T cells (PMID:19190245, PMID:31135971). Physiologically, 4.1R regulates ion transport partners including NHE1, PMCA1b, and cardiac ion currents, and modulates growth-factor and Wnt/β-catenin signaling through partners such as EGFR and ALDOC (PMID:23460639, PMID:22731252, PMID:33242559, PMID:31562860).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1999 High

    Establishing that 4.1R is genetically required to build the red cell membrane skeleton converted it from a biochemically defined component to a functionally essential scaffold.

    Evidence Gene knockout mouse with morphological and biochemical erythrocyte analysis

    PMID:9927493

    Open questions at the time
    • Does not resolve which individual binding interactions account for the spectrin/ankyrin reduction
    • No structural basis provided for the assembly defect
  2. 1999 High

    Discovery that a 135 kDa nonerythroid isoform binds NuMA and partitions to spindle poles revealed an entirely distinct mitotic role beyond the membrane skeleton.

    Evidence Yeast two-hybrid, reciprocal Co-IP, in vitro binding, and co-localization across cell contexts

    PMID:10189366

    Open questions at the time
    • Did not establish whether the interaction is direct in the spindle context or how it is cell-cycle gated
    • Functional requirement of the interaction for spindle assembly not yet tested
  3. 1999 High

    Identifying exon 16 (NLS) and exon 5 (cytoplasmic retention) elements explained how alternative splicing controls subcellular targeting of 4.1R isoforms.

    Evidence Permeabilized-cell import assays and quantitative importin-alpha2 binding measurements with NLS mutagenesis

    PMID:10359596

    Open questions at the time
    • Did not define the regulatory cues that select splice variants in vivo
    • Nuclear function of imported 4.1R not addressed here
  4. 2000 High

    The FERM domain crystal structure provided the molecular logic of multivalent membrane-protein binding and its Ca2+/calmodulin regulation.

    Evidence X-ray crystallography of the 30 kDa domain with functional binding-site mapping

    PMID:10831591 PMID:11017195

    Open questions at the time
    • Structures of full-length or spliced isoforms not determined
    • Conformational coupling between lobes during regulation not visualized
  5. 2000 High

    Mapping the spectrin–F-actin ternary junction and demonstrating ZO-2/tight-junction binding showed 4.1R operates at both the membrane skeleton node and epithelial junctions.

    Evidence In vitro co-sedimentation with domain truncations plus yeast two-hybrid/Co-IP at MDCK tight junctions

    PMID:10874042 PMID:16060676

    Open questions at the time
    • PIP2 regulatory switch tested only in vitro
    • In vivo requirement at epithelial junctions not yet established at this stage
  6. 2006 High

    Defining PIP2 and phosphatidylserine as conformational and competitive regulators established lipid-controlled switching of 4.1R binding specificity.

    Evidence Liposome binding, alanine mutagenesis, and phospholipase-controlled in vitro assays

    PMID:11423550 PMID:16669616

    Open questions at the time
    • Lipid regulation not validated in intact cells
    • How lipid and Ca2+/CaM inputs are integrated is unresolved
  7. 2008 High

    Knockout and pull-down evidence that 4.1R retains XK, Duffy, and Rh defined it as the organizer of a macromolecular junctional complex governing transmembrane protein abundance.

    Evidence 4.1R knockout mouse erythrocyte analysis with in vitro pull-downs and flow cytometry

    PMID:18524950

    Open questions at the time
    • Stoichiometry and assembly order of the complex not determined
    • Direct versus indirect retention of each partner not fully separated
  8. 2004 High

    Direct microtubule binding plus cdc2 phosphorylation at Thr60/Ser679 explained how 4.1R is mobilized to organize mitotic asters and focus spindle poles.

    Evidence In vitro microtubule sedimentation, immunodepletion/add-back reconstitution, cdc2 kinase site mapping, and siRNA spindle-pole phenotype

    PMID:15184364 PMID:15525677

    Open questions at the time
    • The kinase(s) acting in cells and timing of dephosphorylation not defined
    • Relationship between microtubule binding domains and NuMA binding not structurally resolved
  9. 2008 High

    Centrosome localization data linked 4.1R to interphase microtubule anchoring and centrosome separation, broadening its cytoskeletal role across the cell cycle.

    Evidence RNAi with immunofluorescence and cell-cycle analysis showing appendage protein and NuMA mislocalization

    PMID:18212055

    Open questions at the time
    • Direct centrosomal binding partner not defined
    • Mechanism connecting 4.1R loss to G1 arrest unresolved
  10. 2009 High

    Demonstrating direct β-catenin binding and a T cell synapse role showed 4.1R sustains epithelial adhesion and dampens immune activation by directly engaging signaling adaptors.

    Evidence 4.1R-null mouse epithelia plus Co-IP/binding; immunological synapse recruitment with LAT binding and phosphorylation assays in CD4+ T cells

    PMID:19190245 PMID:19376086

    Open questions at the time
    • How a single adaptor switches between adhesion and immune-inhibitory roles not defined
    • Spliceoform usage in each context not fully mapped here
  11. 2011 High

    Nuclear envelope, keratinocyte adhesion, IQGAP1 leading-edge, NHE1 binding, and PKC phosphorylation findings collectively cemented 4.1R as a regulated adaptor across nuclear, migratory, and ion-transport contexts.

    Evidence Co-IP/RNAi for emerin/lamin and IQGAP1; KO keratinocyte adhesion assays; in vitro NHE1 binding; PKC phosphosite mapping with binding assays

    PMID:21486941 PMID:21542582 PMID:21693581 PMID:21750196 PMID:22731252

    Open questions at the time
    • Isoform identity driving each non-erythroid function not always defined
    • Crosstalk between phospho- and lipid-regulation in cells not integrated
  12. 2013 High

    Direct PMCA1b binding with an intestinal calcium-absorption defect, and CLASP2/cortical microtubule regulation, extended 4.1R function to transporter scaffolding and cortical microtubule capture.

    Evidence 4.1R-null mouse calcium physiology with domain-mapped binding; Co-IP plus live MT imaging and GSK3 readout for CLASP2

    PMID:23460639 PMID:23943871

    Open questions at the time
    • Tissue-specific isoform requirements not delineated
    • How 4.1R modulates GSK3 activity locally not mechanistically resolved
  13. 2017 Medium

    A series of studies dissecting the erythroid exon 16 splicing switch (RBFOX2, SF2/ASF, TIA1/Pcbp1/RBM39) explained how the differentiation-specific isoform repertoire of 4.1R is generated.

    Evidence SELEX, minigene splicing assays, splicing-factor Co-IP, U1/U2 snRNP recruitment assays

    PMID:15522963 PMID:16537540 PMID:22083953 PMID:28193846

    Open questions at the time
    • These are mechanisms of 4.1R regulation rather than 4.1R activity itself
    • Single-lab minigene-based evidence not validated at endogenous loci in vivo
  14. 2021 Medium

    Placing 4.1R within the NuMA–LGN–dynein/dynactin spindle-orientation machinery connected its mitotic activity to asymmetric Numb segregation and erythroid cell-fate control.

    Evidence siRNA depletion, gene replacement, Co-IP, and Notch reporter during erythroid differentiation

    PMID:34364872

    Open questions at the time
    • Single lab; in vivo erythropoietic consequences not fully established
    • Direct contribution of each complex member to Numb partitioning not separated
  15. 2024 Low

    Reports of 4.1R binding EGFR, TLR4, ALDOC, VHL, CADM1, and FcεRI signaling components extended its adaptor role into growth-factor, Wnt, metabolic, and innate/adaptive immune signaling.

    Evidence Co-IP, KO mouse phenotypes, ubiquitination/pathway assays, and colony-formation/xenograft models across multiple single-lab studies

    PMID:27780863 PMID:31562860 PMID:31993060 PMID:33242559 PMID:33298314 PMID:38237224

    Open questions at the time
    • Several interactions rest on single Co-IP studies without reciprocal or structural validation
    • Direct versus indirect nature of binding and the responsible isoforms remain undefined
    • Physiological relevance of the signaling roles awaits independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single gene's spliced isoforms are selected and post-translationally gated to partition 4.1R among membrane skeleton, spindle, nucleus, junctions, and signaling complexes in a given cell remains the central open question.
  • No unified model linking isoform/phospho/lipid state to functional destination
  • Structures of full-length isoforms in complex with partners lacking
  • In vivo contributions of non-erythroid functions to physiology underexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0008092 cytoskeletal protein binding 4 GO:0098772 molecular function regulator activity 4 GO:0005198 structural molecule activity 3 GO:0008289 lipid binding 2
Localization
GO:0005634 nucleus 4 GO:0005886 plasma membrane 4 GO:0005856 cytoskeleton 3 GO:0005815 microtubule organizing center 2 GO:0005635 nuclear envelope 1
Pathway
R-HSA-1474244 Extracellular matrix organization 4 R-HSA-162582 Signal Transduction 4 R-HSA-1640170 Cell Cycle 4 R-HSA-168256 Immune System 3
Partners
CTNNB1EMDGYPCLATMPP1NUMA1SLC4A1ZO-2
Complex memberships
NuMA–LGN–dynein/dynactin spindle complexspectrin–actin–4.1R junctional complex

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Crystal structure of the 4.1R N-terminal 30 kDa domain (FERM domain core) reveals a cloverleaf-like architecture with three lobes, each containing a specific binding site for band 3, glycophorin C/D, or p55. Two separate calmodulin (CaM) binding regions are located at the central region: one Ca2+-insensitive alpha-helical site and one Ca2+-sensitive extended-structure site whose binding to CaM weakens 4.1R interactions with target proteins. X-ray crystallography with functional binding assays Nature structural biology High 11017195
2000 Within the 30 kDa domain, sequences encoded by exon 8 constitute the binding interface for glycophorin C (GPC), and sequences encoded by exon 10 constitute the binding interface for p55. 4.1R increases the affinity of p55 binding to GPC by an order of magnitude, and Ca2+/calmodulin binding to 4.1R decreases its affinity for both p55 and GPC in a Ca2+-dependent manner. In vitro binding assays with recombinant domain fragments and calmodulin competition assays The Journal of biological chemistry High 10831591
2000 4.1R forms a ternary complex with spectrin and F-actin at the erythrocyte junctional node; both the intact N-terminus and CH1 domain of the spectrin beta chain bind F-actin and 4.1R. PIP2 greatly enhances the binding of 4.1R to the spectrin beta chain N-terminal region (residues 1-301), suggesting a regulatory switch. In vitro binding/co-sedimentation assays with recombinant domain truncations and liposome PIP2 competition Biochemistry High 16060676
2006 4.1R binds PIP2-containing liposomes through its N-terminal 30 kDa membrane-binding domain; PIP2 binding induces a conformational change. Amino acids K63,64 and K265,266 are required for PIP2 binding. PIP2 selectively enhances 4.1R binding to GPC but inhibits binding to band 3, with no effect on p55 binding. Liposome binding assays, alanine mutagenesis, in vitro pull-down with recombinant proteins Biochemistry High 16669616
2008 Deletion of 4.1R in mouse red cells causes large reduction of actin and loss of cytoskeletal lattice structure. Pull-down assays showed 4.1R associates with XK, Duffy, and Rh transmembrane proteins, in addition to glycophorin C; absence of 4.1R causes selective reduction of these proteins from the membrane, consistent with 4.1R organizing a macromolecular junctional complex. 4.1R knockout mouse analysis, 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 the nuclear mitotic apparatus (NuMA) protein. The minimal interaction sequences map to residues encoded by exons 20 and 21 of 4.1R and residues 1788-1810 of NuMA. 4.1R and NuMA co-localize in the interphase nucleus and redistribute to spindle poles in mitosis; 4.1R forms a complex with NuMA, dynein, and dynactin during cell division. Yeast two-hybrid, in vitro binding assays, co-immunoprecipitation, co-immunolocalization The Journal of cell biology High 10189366
2000 Two 4.1R isoforms (135 kDa and 150 kDa) interact specifically with the tight junction protein ZO-2. 4.1R co-localizes with ZO-2 and occludin at MDCK tight junctions and co-precipitates with ZO-2, ZO-1, and occludin. The interaction maps to exons 19-21 of 4.1R and residues 1054-1118 of ZO-2. This interaction is specific to confluent (tight junction-forming) cells. Yeast two-hybrid, immunocolocalization, co-immunoprecipitation, in vitro binding studies The Journal of biological chemistry High 10874042
1999 Nuclear import of the 4.1R80 isoform requires two distant signals: a basic KKKRER peptide encoded by alternative exon 16 (acting as a weak core NLS) and an acidic EED peptide encoded by alternative exon 5. Both motifs are needed for full importin-mediated nuclear import. 4.1R80 binds importin alpha2 (Rch1) with high affinity (KD = 30 nM), and affinity decreases at least 7–20 fold if either motif is absent. Transfection with epitope-tagged constructs, digitonin-permeabilized cell import assays, resonant mirror protein-protein interaction measurements with recombinant Rch1 Molecular biology of the cell High 10359596
1999 4.1R-null mice generated by gene knockout exhibit moderate hemolytic anemia, abnormal erythrocyte morphology, decreased membrane stability, and reduced expression of spectrin and ankyrin, demonstrating that 4.1R is required for erythroid membrane skeleton assembly. Gene knockout (homologous recombination), morphological and biochemical analysis of erythrocytes The Journal of clinical investigation High 9927493
2011 Protein kinase C activation in intact erythrocytes phosphorylates 4.1R at serine 312 and serine 331. Phosphorylation at either site suppresses 4.1R binding to the cytoplasmic domains of GPC, Duffy, and XK, rendering these transmembrane proteins more easily detergent-extractable. Phosphorylation also weakens 4.1R affinity for beta-spectrin, destabilizing the ternary spectrin-actin-4.1R junctional complex. PKC activation in intact cells, in vitro phosphorylation assays, in vitro protein binding assays with phosphomimetic mutants Biochemistry High 21542582
2001 4.1R binds to phosphatidylserine (PS) through a two-step process: initial interaction via positively charged YKRS residues with the serine head group, followed by tight hydrophobic interaction with fatty acid acyl chains. Association with acyl chains impairs 4.1R binding to calmodulin, band 3, and glycophorin C. 4.1R-PS interaction may regulate intracellular sorting of 4.1R. In vitro liposome binding assays, phospholipase treatments, ionic strength competition, biochemical analyses The Journal of biological chemistry High 11423550
2004 Nonerythroid 135 kDa 4.1R isoforms directly interact with microtubules; both the membrane-binding domain and C-terminal domain mediate tubulin association. 4.1R co-localizes with microtubules in mitotic stages. Immunodepletion of 4.1R from cell-free mitotic extract results in randomly dispersed microtubules instead of organized asters; adding back recombinant 135 kDa 4.1R reconstitutes mitotic asters. In vitro microtubule sedimentation assays, GST pull-downs, immunodepletion from mitotic cell-free extract, reconstitution assays The Journal of biological chemistry High 15184364
2004 4.1R is phosphorylated by p34cdc2 kinase at Thr60 and Ser679 in a mitosis-specific manner. Phosphorylation is essential for targeting 4.1R to spindle poles and for mitotic microtubule aster assembly in vitro. Phosphorylation enhances 4.1R association with NuMA and tubulin. siRNA depletion of 4.1R from HeLa cells impairs efficient mitotic spindle pole focusing. In vitro cdc2 kinase assay, phosphorylation site mapping, siRNA knockdown, mitotic aster reconstitution in vitro Molecular biology of the cell High 15525677
2008 4.1R localizes at centrosomes, specifically at distal/subdistal regions of mature centrioles, in a cell cycle-dependent manner. RNAi depletion of 4.1R perturbs subdistal appendage proteins ninein and outer dense fiber 2/cenexin, reduces interphase microtubule anchoring, causes G1 accumulation in p53-proficient cells, reduces centrosome separation leading to monopolar spindle formation, and causes mislocalization of NuMA. RNAi knockdown, immunofluorescence/confocal microscopy, cell cycle analysis Molecular and cellular biology High 18212055
2009 4.1R expressed in gastric epithelial cells directly associates with adherens junction protein 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 cell-cell contacts and gastric gland organization are disrupted. 4.1R-null mouse analysis, biochemical co-immunoprecipitation/pull-down, histological examination Biochimica et biophysica acta High 19376086
2009 4.1R is recruited to the immunological synapse after TCR stimulation. In 4.1R-deficient CD4+ T cells, LAT phosphorylation and downstream ERK phosphorylation are enhanced, leading to hyperproliferation and increased IL-2/IFNγ production. 4.1R directly binds LAT and thereby inhibits its phosphorylation by ZAP-70. 4.1R-/- mouse model, co-immunoprecipitation, phosphorylation assays, cytokine production measurements Blood High 19190245
2011 4.1R co-immunoprecipitates with nuclear envelope proteins emerin and lamin A/C. RNAi depletion of 4.1R causes nuclear dysmorphology, partial redistribution of emerin to cytoplasm, disorganization of lamin A/C, mislocalization of multiple nuclear subcompartment proteins (MAN1, Tpr, Nup62, NuMA, LAP2α), increased nucleus-centrosome distances, increased β-catenin signaling, and nuclear accumulation of β-catenin. Co-immunoprecipitation, RNAi knockdown, immunofluorescence microscopy in human cells and MEFs Journal of cell science High 21486941
2011 4.1R expression in keratinocytes is required for cell adhesion, spreading, migration, motility, and epidermal wound healing. In 4.1R-/- keratinocytes, surface expression and activity of β1 integrin are reduced, and actin stress fibers and focal adhesions fail to form on fibronectin. 4.1R-/- mouse model, cell adhesion/migration/spreading assays, flow cytometry for β1 integrin surface expression, wound healing assay Journal of cell science High 21693581
2011 4.1R regulates cell migration by localizing to the leading edge; its membrane-binding domain is required for this plasma membrane localization. Co-immunoprecipitation and pull-down identified IQGAP1 as a direct binding partner of 4.1R (via the membrane-binding domain). 4.1R silencing abolishes localization of IQGAP1 to the leading edge, while IQGAP1 is not required for 4.1R localization. siRNA knockdown, co-immunoprecipitation, pull-down assays, live-cell migration assays, immunofluorescence Journal of cell science High 21750196
2013 4.1R directly associates with PMCA1b (plasma membrane calcium ATPase 1b) in enterocytes; the interaction involves the membrane-binding domain of 4.1R and the second intracellular loop and C-terminus of PMCA1b. 4.1R-/- mice show impaired intestinal calcium absorption, reduced PMCA1b expression in enterocytes, and secondary hyperparathyroidism. 4.1R-/- mouse model, co-immunoprecipitation, in vitro direct binding assays with recombinant domains, calcium absorption measurements The Journal of biological chemistry High 23460639
2013 4.1R interacts and co-localizes with cortical CLASP2 and is required for the correct number and dynamics of CLASP2 cortical platforms. 4.1R controls CLASP2 binding to microtubules at the cell edge by locally altering GSK3 activity. In 4.1R-knockdown cells, microtubule plus-ends are not tethered to the cell cortex and lose radial distribution. Co-immunoprecipitation, pull-down assays, siRNA knockdown, live microtubule dynamics imaging, immunofluorescence Journal of cell science High 23943871
2012 4.1R binds directly to the cytoplasmic domain of NHE1 (Na+/H+ exchanger isoform 1) through an EED motif in the 4.1R FERM domain interacting with two clusters of basic residues (K519R and R556FNKKYVKK) in NHE1. Binding affinity (KD = 100-200 nM) is reduced under hypertonic/acidic conditions and upon Ca2+/CaM binding to the 4.1R FERM domain, suggesting electrostatic regulation. In vitro direct binding assays with recombinant proteins, resonant mirror detection, affinity measurements The Biochemical journal High 22731252
2000 4.1R C-terminal domain (22/24 kDa) directly interacts with eIF3-p44, a subunit of the eukaryotic translation initiation factor 3 complex. Depletion of eIF3-p44 from rabbit reticulocyte lysates abolishes efficient cell-free protein translation, suggesting 4.1R may anchor the translation apparatus to the cytoskeleton. Yeast two-hybrid, in vitro binding assays, co-immunoprecipitation, cell-free translation depletion Blood Medium 10887144
2004 A constitutive domain of 4.1R containing heptad repeats of leucine residues is responsible for association with tubulin; this domain is present in all 4.1R isoforms. In T cells, 4.1R associates with interphase microtubules, and ectopic 4.1R expression causes microtubule disorganization. GST pull-down with tubulin, co-sedimentation with taxol-polymerized microtubules, confocal microscopy, transfection assays The Journal of biological chemistry Medium 11579097
2004 4.1R isoforms are present in isolated centrosome preparations and remain at the center of in vitro-assembled microtubule asters. Addition of 4.1R-GST fusion protein increases the number of microtubule asters assembled from isolated centrosomes. Specific 4.1R isoforms that perturb centrosomal distribution of p150Glued and dynein intermediate chain disorganize interphase microtubules after regrowth. Centrosome isolation, in vitro microtubule aster assembly assays, confocal microscopy, transfection Journal of cell science Medium 15564380
2000 A constitutive core region of 4.1R (encoded by constitutive exons, common to all isoforms) can localize to the nucleus and confer nuclear targeting to a cytosolic reporter. Sequences encoded by exon 5 act as a dominant cytoplasmic retention signal (nuclear export signal). When both exon 5 and exon 16 are present, nuclear targeting by exon 16 dominates over exon 5 cytoplasmic retention. Transfection of epitope-tagged natural and engineered 4.1R isoforms in COS-7 cells, immunofluorescence, reporter fusion experiments Journal of cell science Medium 10852827
2002 The exon 5-encoded leucine-rich sequence in 4.1R functions as a nuclear export signal (NES): it binds to export receptor CRM1 in a RanGTP-dependent manner, and two conserved hydrophobic residues are critical for NES function and cytoplasmic localization of 4.1R isoforms containing this sequence. CRM1 binding assays, RanGTP-dependent interaction tests, site-directed mutagenesis, immunofluorescence of exon 5 mutants The Journal of biological chemistry Medium 12427749
1999 The N-terminal 209 amino acid domain (headpiece, HP) encoded from AUG-1 of high molecular weight 4.1R isoforms abrogates nuclear targeting: ATG-1-translated isoforms localize to plasma membrane and endoplasmic reticulum rather than nucleus, and fusing the 209 aa domain to a nuclear 4.1R isoform inhibits its nuclear entry. RT-PCR cloning of ATG-1 isoforms, transient transfection with c-Myc-tagged constructs, immunofluorescence, subcellular fractionation Proceedings of the National Academy of Sciences of the United States of America Medium 10611314
2000 Nonerythroid 4.1R isoforms (~105/110 kDa) in skeletal muscle co-purify in a supramolecular complex with sarcomeric proteins myosin, alpha-actin, and alpha-tropomyosin. In vitro binding assays show 4.1R may interact directly with these contractile proteins through its 10 kDa domain. 4.1R protein decorates A-bands in skeletal muscle. Native complex co-purification, in vitro binding assays with recombinant 10 kDa domain, immunofluorescence/immunohistochemistry Molecular biology of the cell Medium 11071908
2008 4.1R deficiency in mice leads to prolonged Q-T interval and action potential duration, larger/slower Ca2+ transients, increased sarcoplasmic reticulum Ca2+ content, reduced Na+/Ca2+ exchanger current density, faster transient inward current inactivation, and increased persistent Na+ current density. 4.1R KO hearts show reduced NaV1.5α expression, indicating 4.1R modulates cardiac ion transporter function. 4.1R-/- mouse ECG, patch-clamp electrophysiology, Ca2+ transient measurements in isolated myocytes Circulation research Medium 18787192
2006 4.1R deficiency in mice leads to erythrocyte dehydration with reduced K+ and increased Na+ content; Na/H exchange activity is markedly upregulated with increased Vmax, abnormal osmotic dependence, and loss of okadaic acid-induced Na/H exchange activation. This demonstrates that 4.1R physiologically downregulates Na/H exchange activity. 4.1R-/- mouse model, ion transport assays (Na/H exchange, Na-K pump, NKCC cotransport), pharmacological analyses American journal of physiology. Cell physiology Medium 16774987
2006 Fox-2 (RBFOX2) binds to conserved UGCAUG elements in the proximal intron downstream of exon 16 of 4.1R pre-mRNA and activates exon 16 inclusion. Knockdown of Fox-2 by siRNA decreases exon 16 splicing. Fox-2 is expressed in mouse erythroblasts and is a physiological activator of the erythroid differentiation-specific exon 16 splicing switch. SELEX, in vitro RNA binding, HeLa co-transfection minigene assays, siRNA knockdown, immunoblot The Journal of biological chemistry Medium 16537540
2011 RBFOX2 activates exon 16 5' splice site utilization by recruiting U1 snRNP through direct interaction between its C-terminal domain and the zinc finger region of U1C, stabilizing the pre-mRNA–U1 snRNP complex. Strengthening the native weak 5' splice site to consensus abolishes RBFOX2 dependence. Minigene splicing assays, engineered 5' splice site mutants, in vitro protein-protein interaction assays, U1 snRNP recruitment assays Molecular and cellular biology Medium 22083953
2004 SF2/ASF binds a CAGACAT exonic splicing enhancer in exon 16, stimulates exon 16 inclusion in in vitro and in vivo splicing assays, and its expression is upregulated during erythroid differentiation correlating with exon 16 inclusion. UV cross-linking/immunoprecipitation, in vitro complementation splicing assays, MEL cell minigene transfection, immunoblot Blood Medium 15522963
2017 Splicing factors TIA1 and Pcbp1 bind cooperatively to a UUUUCCCCCC motif between the branch point and 3' splice site of exon 16. RBM39 (whose expression rises during erythroid differentiation) enhances the effect of TIA1 and Pcbp1, interacts with U2AF65 and SF3b155, and promotes U2 snRNP recruitment to the branch point, facilitating exon 16 inclusion. In vitro RNA binding assays, minigene splicing assays, co-immunoprecipitation of splicing factors, spliceosome assembly assays Molecular and cellular biology Medium 28193846
2008 Alternatively spliced exon 5 of the 4.1R FERM domain encodes a second binding site for p55, distinct from the exon 10-encoded site; both bind independent sites within the D5 domain of p55. Inclusion of exon 5 is necessary for membrane targeting of the full-length 135 kDa 4.1R isoform in epithelial cells. Competition binding assays, Surface Plasmon Resonance, transfection/immunofluorescence for localization Biochimica et biophysica acta Medium 18952129
2003 4.1R interacts with merlin/4.1B interactors including CD44 and betaII-spectrin in meningioma cells. Overexpression of 4.1R reduces meningioma cell proliferation, and 4.1R membrane localization increases under growth arrest conditions. Co-immunoprecipitation, Western blot, cell proliferation assays, immunofluorescence Neurobiology of disease Medium 12901833
2009 4.1R directly associates with adherens junction protein beta-catenin via its membrane-binding domain (specifically the armadillo repeats 1-2 of beta-catenin). Epithelial-specific 4.1R isoforms containing exon 17b (4.1R+17b) are exclusively co-localized with AJs; exon 17b-encoded peptide provides a bispecific interaction with the actin cytoskeleton and promotes fodrin-actin complex formation. Depletion of 4.1R+17b or overexpression of 4.1R-17b reduces junctional actin and spectrin and impairs E-cadherin assembly during AJ reassembly. Co-immunoprecipitation, pull-down assays with recombinant domains, siRNA knockdown, calcium switch AJ reassembly assay, immunofluorescence The Journal of biological chemistry Medium 31776189
2021 4.1R functions as a member of the NuMA-LGN-dynein/dynactin complex to regulate mitotic spindle orientation during erythroid differentiation. The 4.1R-NuMA interaction is required for asymmetric segregation of Numb to daughter cells; disruption of this complex increases Notch signaling and decreases erythroblast population. siRNA depletion, gene replacement, co-immunoprecipitation, immunofluorescence, Notch signaling reporter The Journal of biological chemistry Medium 34364872
2015 4.1R directly binds Kell blood group protein; pull-down and co-immunoprecipitation from erythrocyte membranes showed a direct interaction, with the R46R motif in the Kell juxta-membrane region binding to lobe B of the 4.1R FERM domain. 4.1R deficiency is associated with reduction of Kell, XK, DARC, and the glycosylated form of urea transporter B. In vitro pull-down, co-immunoprecipitation, recombinant domain-mapping British journal of haematology Medium 26455906
2016 4.1R associates with VHL protein and, when overexpressed, reverses VHL-mediated ubiquitination and degradation of myogenin, stabilizing myogenin protein levels. 4.1R depletion impairs skeletal muscle differentiation, decreasing myosin heavy and light chains, caveolin-3, and myogenin protein (but not mRNA). siRNA knockdown, co-immunoprecipitation, ubiquitination assays, myoblast differentiation assays, 4.1R-/- MEF MyoD-induced differentiation The Journal of biological chemistry Medium 27780863
2020 In non-small cell lung cancer, EPB41 protein directly associates with ALDOC (aldolase C). Loss of EPB41 releases ALDOC from the EPB41-ALDOC complex, disassembling the beta-catenin destruction complex, reducing beta-catenin proteolytic degradation, and activating Wnt/β-catenin target oncogenes. Co-immunoprecipitation, in vitro interaction assays, beta-catenin stability and localization assays, tumor xenograft model Cancer letters Medium 33242559
2019 4.1R binds directly to EGFR and reduces EGFR phosphorylation/activation in keratinocytes. 4.1R knockout augments EGFR-mediated Akt/ERK signaling, causing keratinocyte hyperproliferation that is reversed by EGFR or MEK inhibitors. Co-immunoprecipitation, immunofluorescence, 4.1R-/- mouse keratinocytes, pharmacological inhibitors Experimental cell research Medium 31562860
2024 4.1R directly interacts with TLR4 and inhibits AKT/HIF-1α signaling. 4.1R deficiency enhances glycolytic metabolism via upregulation of PKM2 and promotes M1 macrophage polarization, exacerbating sepsis-induced liver injury. Co-immunoprecipitation, 4.1R-/- mice, glycolysis assays, PKM2 and HIF-1α pathway analysis International immunopharmacology Low 38237224
2020 4.1R is required for FcεRI-mediated mast cell activation. In 4.1R-KO mast cells, antigen-induced phosphorylation of SYK and downstream signaling molecules (LAT1, PLCγ1, SHP1, SHIP, p38, ERK, JNK, STAT5, CBL, mTOR) are reduced while FcεRI β and γ subunit phosphorylation is unaffected. LAT1 and LAT2 are both present in 4.1R immunocomplexes. 4.1R-KO mouse BMMCs, phosphorylation assays, co-immunoprecipitation, degranulation and calcium response assays, passive cutaneous anaphylaxis in vivo Frontiers in immunology Medium 31993060
2020 CADM1 recruits 4.1R to the plasma membrane of small-cell lung cancer cells through its cytoplasmic 4.1 protein-binding motif. Knockdown of 4.1R suppresses the CADM1-enhanced colony formation, indicating 4.1R is required for the oncogenic role of CADM1 in SCLC. CADM1 deletion/point mutant analysis, siRNA knockdown, soft agar colony formation assay, immunofluorescence Biochemical and biophysical research communications Low 33298314
2001 An 80 kDa 4.1R polypeptide is enriched ~11-fold in forebrain postsynaptic density (PSD) preparations. Blot overlay assays identified neurofilament L and alpha-internexin as 4.1R-binding proteins in PSDs; a complex containing 80 kDa 4.1R, alpha-internexin, and neurofilament L was immunoprecipitated from brain extract. Subcellular fractionation, blot overlay assays, co-immunoprecipitation from brain extract European journal of biochemistry Low 11179975
2019 4.1R negatively regulates CD8+ T cell activation by directly binding LAT (co-immunoprecipitation), inhibiting LAT phosphorylation and downstream ERK signaling; 4.1R-/- CD8+ T cells show enhanced proliferation, IL-2 and IFNγ secretion, and T cell-dependent immune responses. 4.1R-/- mouse, co-immunoprecipitation, phosphorylation assays, proliferation and cytokine assays Immunology Medium 31135971

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 139 26407012
2004 Hereditary elliptocytosis: spectrin and protein 4.1R. Seminars in hematology 128 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 125 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 105 11017195
1999 Protein 4.1R-deficient mice are viable but have erythroid membrane skeleton abnormalities. The Journal of clinical investigation 103 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
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 70 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
2009 Cytoskeletal protein 4.1R negatively regulates T-cell activation by inhibiting the phosphorylation of LAT. Blood 38 19190245
2007 Regulated Fox-2 isoform expression mediates protein 4.1R splicing during erythroid differentiation. Blood 38 17715393
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
2016 Integrative Functional Genomics Implicates EPB41 Dysregulation in Hepatocellular Carcinoma Risk. American journal of human genetics 32 27453575
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
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
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 28 23460639
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
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
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 27 18212055
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
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
2021 Suppression of 4.1R enhances the potency of NKG2D-CAR T cells against pancreatic carcinoma via activating ERK signaling pathway. Oncogenesis 22 34548478
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
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
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 19 18921992
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 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
2022 Circular RNA EPB41 expression predicts unfavorable prognoses in NSCLC by regulating miR-486-3p/eIF5A axis-mediated stemness. Cancer cell international 15 35725615
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
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
2016 Protein 4.1R Influences Myogenin Protein Stability and Skeletal Muscle Differentiation. The Journal of biological chemistry 9 27780863
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
2024 Protein 4.1R regulates M1 macrophages polarization via glycolysis, alleviating sepsis-induced liver injury in mice. International immunopharmacology 8 38237224
2021 The protein 4.1R downregulates VEGFA in M2 macrophages to inhibit colon cancer metastasis. Experimental cell research 8 34717920
2020 Cytoskeleton protein 4.1R regulates B-cell fate by modulating the canonical NF-κB pathway. Immunology 8 32852059
2019 Protein 4.1R negatively regulates CD8+ T-cell activation by modulating phosphorylation of linker for activation of T cells. Immunology 8 31135971
2020 Protein 4.1R affects photodynamic therapy for B16 melanoma by regulating the transport of 5-aminolevulinic acid. Experimental cell research 7 33385415
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
2018 Lnc-EPB41-Protein Interactions Associated with Congenital Pouch Colon. Biomolecules 6 30227690
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
2017 Protein 4.1R is Involved in the Transport of 5-Aminolevulinic Acid by Interaction with GATs in MEF Cells. Photochemistry and photobiology 5 28881432
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
2007 Neuroacanthocytosis associated with a defect of the 4.1R membrane protein. BMC neurology 5 17298666
1991 Two RFLPs in the human protein 4.1 gene (EL1). Nucleic acids research 5 1682895

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