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FLASH GENE
Symbol MYBPC3 contributors: mlc/npt - updated : 11-01-2023
HGNC name myosin binding protein C, cardiac
HGNC id 7551
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • four N-terminal regulatory domains, C0-C1-m-C2 (C0C2), influencing actin and myosin interactions, the basic contractile proteins of muscle
  • a cardiac-specific Ig-like domain C0, interacting with the regulatory light chain of myosin, thus placing the N terminus of the protein in proximity to the motor domain of myosin
  • C0 and C1 domain can each bind to the same two distinctly different positions on F-actin
  • seven immunoglobulin Ig C2 domains
  • third immunoglobulin domain of the cardiac isoform (cC2), having the beta-sandwich structure expected from a member of the immunoglobulin fold, and so-called "motif," located between the second and third immunoglobulin modules of the cardiac isoform, that is required for its Ca2+-dependent interaction with calmodulin
  • a M-domain, the major regulatory subunit of cardiac myosin-binding protein-C (MYBPC3) that modulates actin and myosin interactions to influence muscle contraction
  • three fibronectin, type III domains
  • two myosin binding sites, one close to the N terminus and the other at the C terminus
  • C terminal region binds to myosin rods and stabilizes thick filament structure
    • HOMOLOGY
    Homologene
    FAMILY
  • immunoglobulin family
  • MYBP subfamily
    • CATEGORY motor/contractile , structural protein
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton
    text sarcomeric protein in the A band of sarcomeres (the cross-bridge-bearing zone (C region) of A bands in striated muscle)
    basic FUNCTION
  • acting as a cross-bridge between myosin and titin, mediating adrenergic stimulation of cardiac contraction
  • accessory protein of striated muscle sarcomeres that is vital for maintaining regular heart function
  • multidomain protein present in the thick filaments of striated muscles and is involved in both sarcomere formation and contraction regulation
  • critical nodal point that has both important structural and signaling roles and whose modifications are known to cause significant human cardiac disease
  • myofibrillar protein important for normal myocardial contractility and stability
  • functions likely as a physiological brake on contraction by positioning myosin heads away from the thin filament, a constraint which is removed upon adrenergic stimulation or MYBPC3 ablation
  • multi-domain (C0-C10) protein that regulates heart muscle contraction through interaction with myosin, actin and other sarcomeric protein
  • role of LRP1 in the regulation and turnover of synaptic proteins, which may contribute to the reduced dendritic branching and to the neurological phenotype observed in the absence of LRP1
  • is dispensable for the development of skeletal muscle with no functional or structural consequences in the adult myocyte, and skeletal isoforms can transcomplement in the heart in the absence of MYBPC3
  • activates thin filaments and inhibits thick filaments in heart muscle cells
  • thick filament-associated protein that seems to contribute to the regulation of cardiac contraction through interactions with either myosin or actin or both
  • regulates the rate and force of contraction in mammalian myocardium
  • signaling node in cardiac myocytes that contributes to the maintenance of sarcomeric structure and regulation of contraction and relaxation
  • is a potent modulator of cardiac contractility
  • intrinsic role of MYBPC3 in maintaining cardiac fibroblast homeostasis and disruption of MYBPC3 in these cells contributes to the disease pathogenesis of hypertrophic cardiomyopathy (HCM)
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of the thick filament that appears to tune these mechanochemical interactions by its N-terminal domains transiently interacting with actin and/or the myosin S2 domain, sensitizing thin filaments to calcium and governing maximal sliding velocity
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to beta myosin S2
  • binding to titin
  • interacts with actin via a single, moderate affinity site localized to the C-terminal region of the protein
  • PDE4DIP is a novel A-kinase anchoring protein involved in the phosphorylation of MYBPC3
  • CALM1 may act as a structural conduit that links MYBPC3 with Ca(2+) signaling pathways to help coordinate phosphorylation events and synchronize the multiple interactions between MYBPC3, myosin, and actin during the heart muscle contraction
    • cell & other
    REGULATION
    Other competency for phosphorylation at multiple sites in MYBPC3 is a prerequisite for normal beta-adrenergic responsiveness
    ASSOCIATED DISORDERS
    corresponding disease(s) CFMH4 , CMD1MM
    related resource FHC Mutation Database
    Susceptibility
  • to chronic risk of heart failure
  • to idiopathic dilated cardiomyopathy
    • Variant & Polymorphism insertion/deletion , other
  • 25-bp deletion, a common MYBPC3 variant in South Asians, is associated with chronic risk of heart failure (Dhandapany 2009)
  • mutated in idiopathic dilated cardiomyopathy (Moller 2009)
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • elevated oxidative stress in MYPBC3-mutated dilated cardiomyopathy (DCM) mice, which may exacerbate the development of heart failure
  • mechanism leading to cardiac dilation in homozygous Mybpc3(-/-) mice is primarily myocyte hyperplasia, and mechanism leading to hypertrophic cardiomyopathy in heterozygous Mybpc3(+/-) individuals is myocyte hypertrophy (increased cell size)
  • autophagy is impaired in Mybpc3-targeted knockin mice, and activation of autophagy ameliorated the cardiac disease phenotype in this mouse model