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FLASH GENE
Symbol NEB contributors: mct/npt/pgu - updated : 23-11-2013
HGNC name nebulin
HGNC id 7720
Corresponding disease
NEM2 nemaline myopathy 2
Location 2q23.3      Physical location : 152.341.854 - 152.591.001
Synonym symbol(s) NEM2, NEB177D, FLJ39568, FLJ39584, DKFZp686C1456, FLJ11505, FLJ36536
DNA
TYPE functioning gene
STRUCTURE 249.15 kb     181 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
Map cen - D2S381 - D2S151 - NEB /D2S2236 - D2S356 - D2S321 - D2S141 - qter
Physical map
LOC200583 2q23.2-q23.3 similar to Polyadenylate-binding protein 1 (Poly(A)-binding protein 1) (PABP 1) ACVR2 2q22.2-q23.3 activin A receptor, type II ORC4L 2q22-q23 origin recognition complex, subunit 4-like (yeast) MBD5 2q23.2 methyl-CpG binding domain protein 5 DKFZP566F2124 2q23.3 DKFZP566F2124 protein UBBP3 2q22.3 ubiquitin B pseudogene 3 LOC344172 2q23.3 similar to ubiquitin specific protease 8 LOC391451 2 similar to Kinesin heavy chain isoform 5C (Kinesin heavy chain neuron-specific 2) KIF5C 2q22.3-q32 kinesin family member 5C LOC151276 2q23.3 thioredoxin 1 pseudogene 1 LOC130576 2q23.3 hypothetical protein LOC130576 MGC52057 2q23.3 hypothetical protein MGC52057 CL25022 2q23.3 hypothetical protein CL25022 FLJ32955 2q23.3 hypothetical protein FLJ32955 ARHE 2q23.3 ras homolog gene family, member E LOC339782 2q23.3 hypothetical LOC339782 LOC344332 2q23.3 similar to Fatty acid-binding protein, epidermal (E-FABP) (Psoriasis-associated fatty acid-binding protein homolog) (PA-FABP) LOC389054 2 similar to FLJ45645 protein NMI 22q13.3 N-myc (and STAT) interactor TNFAIP6 2q23.3 tumor necrosis factor, alpha-induced protein 6 DKFZP434D193 2q24.1 DKFZP434D193 protein NEB 2q21.2-q22 nebulin ARL5 2q23.3 ADP-ribosylation factor-like 5 CACNB4 2q22-q23 calcium channel, voltage-dependent, beta 4 subunit STAM2 2q24.1 signal transducing adaptor molecule (SH3 domain and ITAM motif) 2 NUDCP1 2q23-q24 nuclear distribution gene C homolog (A. nidulans) pseudogene 1 FNBP3 2q23.3 formin binding protein 3 MGC33864 2q24.1 ADP-ribosylation-like factor 6-interacting protein 6 LOC391452 2 similar to ATP synthase B chain, mitochondrial precursor LOC391453 2 similar to ribosomal protein L23a REPRIMO 2q24.1 candidate mediator of the p53-dependent G2 arrest GALNT13 2q24.1 UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 13 (GalNAc-T13) KCNJ3 2q24.1 potassium inwardly-rectifying channel, subfamily J, member 3 LOC391454 2 similar to ATP synthase alpha chain, mitochondrial precursor NR4A2 2q22-q23 nuclear receptor subfamily 4, group A, member 2 LOC389055 2 LOC389055 GPD2 2q24.1 glycerol-3-phosphate dehydrogenase 2 (mitochondrial) LOC391455 2 similar to Acidic ribosomal phosphoprotein P0
RNA
TRANSCRIPTS type messenger
text complex splicing resulting in isoform with different number of repeats tissue and stage specific
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
149 - 20644 - 6669 - 2004 15266303
181 - 26202 - 8525 - 2004 15266303
exchange of exon 143 for exon 144
181 - 26202 - 8525 - 2004 15266303
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Digestivemouth   highly
Endocrineneuroendocrinepituitary  highly
Respiratoryrespiratory tractlarynx  highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal specific
cell lineage
cell lines
fluid/secretion
at STAGE
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
  • 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