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FLASH GENE
Symbol NEB contributors: mct/npt/pgu - updated : 23-11-2013
HGNC name nebulin
HGNC id 7720
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • an acidic N-terminal domain
  • 35-AAs module repeats (185 small tandem repeats of approximately 35 AA, differentially expressed)
  • a linker domain
  • a glutamic acid-rich domain
  • a serine-rich domain
  • a SH3 domain at the C terminus localized within the IZI junction (SSVLYKEN motif), binding to desmin and may directly connect the titin and nebulin filament systems via an interaction with the spring-like PEVK domain from the I-band region of titin (C-terminal region of nebulin interacted with the C-terminus of archvillin , that is a novel ligand of proline-rich regions of XIRP1 and XIRP2
    • HOMOLOGY
    Homologene
    FAMILY
    CATEGORY regulatory , structural protein
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microfilament
    text C terminal integrating into the Z disc lattice and a N terminus projecting into the I-band
    basic FUNCTION
  • involved in the length regulation of the thin filament
  • giant muscle protein may be involved in maintaining the structural integrity of sarcomeres and the membrane system associated with the myofibrils
  • bind and stabilize f-actin
  • giant filamentous protein extending along the entire length of the thin filament, providing a blueprint for muscle thin filament assembly
  • can be considered as a fourth filament system of the sarcomere (after thin, thick and titin filaments)
  • as in skeletal muscle, may have a role as an actin filament stabilizer or length regulator in neurons of the human brain, although patients with NEB mutations usually have normal cognition
  • giant sarcomeric protein that plays a pivotal role in skeletal muscle contractility by specifying thin filament length and function
  • nebulin SH3 domain plays a role in bearing high active stress and perhaps in fine-tuning the excitation-contraction coupling mechanism
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • nebulin–WASL complex caused actin nucleation for unbranched actin filament formation from the Z bands without the Arp2/3 complex
  • both DES and NEB form complex filament systems in muscle cells that synergistically collaborate to integrate the myofibril contractile machinery to the IF cytoskeletal network
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to actin
  • interacting with titin (TTN)
  • interaction with SVIL (may provide a direct link between the sarcolemma and myofibrillar Z-lines)
  • WASL binds to the nebulin C-terminal region by IGF1 stimulation
  • interacts with desmin DES) through multiple sites to provide efficient stability to satisfy the dynamic contractile activity of myocytes
  • temporally restricted interaction of Xin-repeat proteins (XIRP1, XIRP2) with nebulin/nebulette during early stages of myofibril development that is lost upon further maturation
    • cell & other
  • 15 helical actin binding
    • REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) NEM2
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • in Neb(deltaExon55) mice the regulation of contraction is impaired, as evidenced by marked changes in crossbridge cycling kinetics and by a reduction of the calcium sensitivity of force generation