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FLASH GENE
Symbol EPB41 contributors: mct - updated : 13-09-2016
HGNC name erythrocyte membrane protein band 4.1 (elliptocytosis 1, RH-linked)
HGNC id 3377
Corresponding disease
EL1 hereditary elliptocytosis, type 1
Location 1p35.3      Physical location : 29.213.602 - 29.446.558
Synonym name
  • erythrocyte surface protein band 4.1
  • protein 4.1
  • Synonym symbol(s) EPB4.1, HE, EL1, 4.1R, E41P, P4.1
    DNA
    TYPE functioning gene
    STRUCTURE 233.33 kb     21 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure
  • including the alternative exon 17a in the muscle, 17B in epithelial cells
  • three alternative promoters
  • MAPPING cloned Y linked   status confirmed
    RNA
    TRANSCRIPTS type messenger
    text resulting in a complex expression pattern from extensive alternative pre m-RNA splicing, two possible initiation sites and post translational modification
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 - 5961 97 864 - 2009 18952129
    21 splicing initiation site 5999 - 641 - 2009 18952129
    19 splicing 5823 - 588 - 2009 18952129
    18 - 5782 - 601 - 2009 18952129
    15 - 2423 81.7 720 expressed at late stages of erythroid differentiation and is the principal component of mature erythrocytes 2009 18691159
  • 4.1R(80)
  • bound to cytoplasmic domains of GPC (glycophorin C) and band 3
  • 17 - 5694 - 775 - 2009 18952129
    - - - 135 - expressed at distinct stages of terminal erythroid differentiation 2009 18691159
  • also called 4.1R(135) isoform
  • includes an additional 209 AAs designated as the HP (head-piece) at the N-terminus of 4.1R(80), that mediates the Ca2+-dependent binding
  • bound to cytoplasmic domains of GPC (glycophorin C) and band 3
  • able to assemble on to the membrane of early erythroblasts suggesting that its ability to bind to membrane proteins is sufficient for its membrane localization
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart     Homo sapiens
    Digestiveintestinelarge intestinecolon   Homo sapiens
    Nervousbrainhindbrainmedulla oblongata  
     meningesleptomeninges   
    Urinarykidney     Mus musculus
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticerythrocyte
    Digestiveenterocyte Homo sapiens
    Digestiveepithelial cell Homo sapiens
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal FERM (EPB41, ezrin, radixin, moesin) domain cysteine-rich, basic charged globular module, interacting with MPP1
  • a spectrin-actin-binding domain (SABD)
  • a glycophorin/calmodulin binding domain
  • a C terminal region
  • a spectrin-actin-binding domain
  • a protein-saccharide modification structure
  • a nuclear localization signal (NLS)
  • conjugated GlycoP
    HOMOLOGY
    Homologene
    FAMILY
  • ezrin/moesin/radixin-like (ERM) family
  • protein 4.1 family
  • CATEGORY adaptor
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus
    text
  • localizes at centrosomes to distal/subdistal regions of mature centrioles in a cell cycle-dependent pattern
  • present in subcellular fractions enriched in intercalated discs, in a complex resistant to solubilization under non-denaturing conditions
  • basic FUNCTION
  • critical for the membrane-associated cytoskeleton structure of erythocytes, playing a key role in regulating membrane physical properties of mechanical stability and deformability by stabilizing spectrin-actin interaction
  • regulating in central neurons, the stabilization of AMPA receptors on the neuronal surface at the postsynaptic density
  • responding and participating in reorganization of membrane-cytoplasmic interactions
  • makes crucial contributions to the structural integrity of centrosomes and mitotic spindles which normally enable mitosis and anaphase to proceed with the coordinated precision required to avoid pathological events
  • promote the mechanical stability of plasma membranes by interaction with the cytoskeletal proteins spectrin and actin and required for the cell surface expression of a number of transmembrane proteins
  • role in modulating the functional properties of several cardiac ion transporters with consequences on cardiac electrophysiology and with possible significant roles during normal cardiac function and disease
  • its expression involves transcriptional regulation coupled with a complex splicing regulatory network
  • required for the stable cell surface accumulation of a number of erythrocyte membrane proteins
  • have roles in the accumulation of at least three classes of ion channel
  • EPB41, EPB41L1, EPB41L2 proteins are differentially compartmentalised in the heart, and they form specific complexes with proteins central to cardiomyocyte Ca(2+) metabolism
  • regulates SLC9A1 activity through a direct protein-protein interaction that can be modulated by intracellular pH and Na(+) and Ca(2+) concentrations
  • adapter that link actin-based cytoskeleton to plasma membrane proteins
  • component of cell membrane cytoskeleton, that plays a part in erythrocyte shape and deformability
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of a complex tissue-specific and developmentally regulated erythroid and non erythroid expression pattern
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • FKBP2
  • binding F-actin to spectrin dimers
  • binding CNTNAP1 and CNTNAP2
  • interacting with actin and bind to the N-terminal region (residues 1-301) of the spectrin beta chain, to the separate CH1 and CH2 domains
  • interacting through te FERM domain with MPP1 (binds to a 51-AAs peptide, encoded by exon 10, located within the FERM domain of EPB41)
  • in epithelia, interacts with the store-operated channel TRPC4
  • binds directly to the SLC9A1cd (cytoplasmic domain of SLC9Q1) through the interaction of an EED motif in the EPB41 FERM (4.1/ezrin/radixin/moesin) domain
  • functional role for EPB41 in small intestinal calcium absorption through regulation of membrane expression of PMCA1
  • role for the scaffolding protein EPB41 in locally controlling CLASP2 behavior, CLASP2 cortical platform turnover and GSK3 activity, enabling correct microtubule organization and dynamics essential for cell polarity
  • NUMA1 anaphase localization is independent of GPSM2 and EPB41 interactions, revealing two distinct mechanisms responsible for NUMA1 cortical recruitment at different stages of mitosis
  • cell & other
    REGULATION
    Other developmentally regulated
    ASSOCIATED DISORDERS
    corresponding disease(s) EL1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    in neuroblastoma
    tumoral     --low  
    in sporadic meningioma
    tumoral     --low  
    in hepatocellular carcinoma
    Susceptibility
  • to mandibular prognathism (MP)
  • to hepatocellular carcinoma
  • Variant & Polymorphism other
  • Four SNPs located in the EPB41 gene showed possible allelic and genotypic associations with MP
  • SNP, rs157224G>T, associated to risk of hepatocellular carcinoma
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS