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FLASH GENE
Symbol NEBL contributors: mct - updated : 20-05-2014
HGNC name nebulette
HGNC id 16932
Location 10p12.31      Physical location : 21.068.904 - 21.463.116
Synonym name
  • nebulette, nebulin-like protein
  • LIM-nebulette
  • actin-binding Z-disk protein
  • Synonym symbol(s) LASP2, LNEBL, RP11-56H7.1
    DNA
    TYPE functioning gene
    STRUCTURE 394.22 kb     28 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    motif repetitive sequence   ALU
    MAPPING cloned Y linked N status provisional
    Map pter - VIM - NRP1 - MSRB2 - NEBL - PLXDC2 - ARL5B - CACNB2 - CUBN - cen
    Authors Gene Map, Katoh(03)
    Physical map
    PTER 10p12 phosphotriesterase related LOC389941 10 similar to Gliacolin RSU1 10p13 Ras suppressor protein 1 CUBN 10p12.1 cubilin (intrinsic factor-cobalamin receptor) DNMT2 10p15.1 DNA (cytosine-5-)-methyltransferase 2 VIM 10p13 vimentin ST8SIA-VI 10p13 alpha 2,8-sialyltransferase PTPLA 10p14-p13 protein tyrosine phosphatase-like (proline instead of catalytic arginine), member a STAM 10p14-p13 signal transducing adaptor molecule (SH3 domain and ITAM motif) 1 LOC340843 10p13 similar to protein of unknown function LOC340893 10p13 similar to protein of unknown function MRC1 10p13 mannose receptor, C type 1 SLC39A12 10p13 solute carrier family 39 (zinc transporter), member 12 CACNB2 10p12 calcium channel, voltage-dependent, beta 2 subunit NOPD1 10p13 nucleolar protein (NOL1/NOP2/sun) and PUA domains 1 ARL8 10p13 ADP-ribosylation factor-like 8 LOC389942 10 similar to Programmed cell death protein 8, mitochondrial precursor (Apoptosis-inducing factor) LOC387635 10 similar to ubiquitin-conjugating enzyme E2 variant 1 isoform a; DNA-binding protein LOC340895 10p12.33 similar to apical early endosomal glycoprotein precursor LOC387636 10 LOC387636 PLXDC2 10p12.33 plexin domain containing 2 LOC220998 10p12.33 similar to Protein C21orf59 NEBL 10p12 similar to Protein C21orf59 LOC387637 10 similar to eukaryotic initiation factor 4B LOC387638 10 LOC387638 LOC387639 10 LOC387639 LOC219689 10p12.33 similar to putative RNA methyltransferase LOC387640 10 similar to RIKEN cDNA E130012A19 MLLT10 10p12 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 10 DNAJC1 10p12.31 DnaJ (Hsp40) homolog, subfamily C, member 1 LOC340900 10p12.32 similar to Hypothetical protein FLJ10213 LOC338098 10p12 proteasome activator subunit 2 pseudogene LOC389943 10 similar to ribosomal protein L31 BMI1 10p13 B lymphoma MO-MLV insertion region (mouse) C10orf8 10pter-q22.1 chromosome 10 open reading frame 8 SPAG6 10p12-p11.2 sperm associated antigen 6 PIP5K2A 10p11.23 phosphatidylinositol-4-phosphate 5-kinase, type II, alpha FLJ32827 PILB 10p12 phosphatidylinositol-4-phosphate 5-kinase, type II, alpha LOC143371 10p12.31 tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta pseudogene PTF1A 10p12.31 pancreas specific transcription factor, 1a LOC387642 10 similar to RIKEN cDNA 4921522E24 MGC46732 LOC220213 10p12.31 hypothetical protein LOC220213 DKFZP761L0424 ARHGAP21 10p12.31 Rho GTPase activating protein 21 PRTFDC1 10p12.31 phosphoribosyl transferase domain containing 1 MGC26778 FLJ22002 10p12.31 hypothetical protein FLJ22002 GPR158 10p12.31 G protein-coupled receptor 158
    RNA
    TRANSCRIPTS type messenger
    text isoforms with different number of C repeats tissue and stage specific
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 splicing 6956 - 270 non-muscle isoform, widely expressed and highly enriched in neuronal tissue. 2009 18677772
  • exons 1a-4a, 24, 27, and 28
  • LASP2 or V2
  • 28 - 9231 - 1014 - 2004 15004028
  • NEBL or V1
  • sarcomeric isoform
  • - - splicing - - 980 - 2004 15004028
    lacking exon 6, 102bp
    7 - 6954 - 224 - 2004 15004028
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Nervousbrainforebraincerebral lobefrontal 
     spinal cord    
    Respiratorylung    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiac  
    Nervouscentral   
    cell lineage
    cell lines pancreatic cancer cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • 23 N terminal actin-binding repeats of 35 residues (S2XXYK consensus sequence)
  • a serine rich domain with potential phosphorylation sites
  • a C terminal SH3 domain, that is novel ligand of proline-rich regions of XIRP1 and XIRP2
  • HOMOLOGY
    interspecies homolog to murine Lasp2
    intraspecies homolog to extremely similar to the C terminus of nebulin
    Homologene
    FAMILY LASP family proteins, nebulin family of actin binding proteins.
    CATEGORY motor/contractile , structural protein
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytoskeleton,microfilament
    text
  • binding the Z band to actin filaments
  • C terminal integrating into the Z disc lattice and a N terminus projecting into the I-band
  • basic FUNCTION
  • playing an important role in the assembly of the Z- disc
  • may play an important role in the organization of focal adhesions with LASP1, and zyxin
  • LASP1 and NEBL, are important during early embryo- and fetogenesis and are highly expressed in the central nervous system of the adult
  • dynamic focal adhesion protein that increases the rate of attachment and spreading of fibroblasts on fibronectin coated surfaces
  • NEBL and LASP1 have distinct roles in the actin cytoskeleton
  • cardiac-specific isoform of the giant actin-binding protein nebulin
  • has an important role in coordinating and regulating the composition and dynamics of focal adhesions
  • sarcomeric Z-disk protein involved in mechanosensing and force generation via its interaction with actin and tropomyosin-troponin complex
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • actin binding
  • interacting with LASP1 and ZYX (SH3 domains from LASP1 and nebulin can also interact with zyxin, but the SH3 domains from more distantly related proteins such as vinexin and SNX9 do not)
  • importance of the NEBL-TPM1 interactions in the maintenance and stability of the thin filaments
  • interplay between LASP2 and LASP1 could be an adhesion regulatory mechanism
  • 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
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    with KMT2A in a case of acute myeloid leukemia in an infant
    Susceptibility
  • to non familial idiopathic dilated cardiomyopathy (DCM)
  • to endocardial fibroelastosis
  • Variant & Polymorphism SNP
  • N654K, homozygotes KK susceptibility
  • different mutations in NEBL trigger specific mechanisms, converging to a common pathological cascade leading to endocardial fibroelastosis and DCM
  • Candidate gene
    Marker
  • effects of NEBL mutations on sarcomere ultrastructure, cellular contractile function, and calcium homeostasis in preclinical dilated cardiomyopathy (DCM), suggesting that these abnormalities correlate with detectable myocardial wall motion patterns
  • Therapy target
    ANIMAL & CELL MODELS