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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
Corresponding disease
CFMH4 cardiomyopathy, familial hypertrophic, 4
CMD1MM cardiomyopathy, dilated, 1MM
Location 11p11.2      Physical location : 47.352.957 - 47.374.253
Synonym name
  • cardiac MyBP-C
  • cardiomyopathy, hypertrophic 4
  • protein C, cardiac
    • Synonym symbol(s) FHC, MYPC, MYBP-C, DKFZp779E1762, MYBPC, cMyBP-C
    DNA
    TYPE functioning gene
    STRUCTURE 21.30 kb     35 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    text with two isoforms cardiac and fast skeletal muscle
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    35 - 4217 150 1274 - 2011 21257752
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheartventricle    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal   Homo sapiensFetal
    Muscularstriatumcardiac   Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    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