Nebulette
Lua error in Module:Infobox_gene at line 53: attempt to index field 'wikibase' (a nil value). Nebulette is a cardiac-specific isoform belonging to the nebulin family of proteins. It is encoded by the NEBL gene. This family is composed of 5 members: nebulette, nebulin, N-RAP, LASP-1 and LASP-2. Nebulette localizes to Z-discs of cardiac muscle and appears to regulate the length of actin thin filaments.
Structure
[edit | edit source]Nebulette is a 116.4 kDa protein composed of 1014 amino acids.[1][2] As a member of the nebulin family of proteins, nebulette is characterized by 35 amino acid stretches of ‘‘nebulin repeats’’, which are actin binding domains containing a conserved SDxxYK motif.[3] Like nebulin, nebulette has an acidic region with unknown structure at its N-terminus, and a serine-rich region adjacent to an SH3 domain at its C-terminus.[4] Though nebulette shares structural features with nebulin, nebulin is expressed preferentially in skeletal muscle and has an enormous size (600-900 kDa), while nebulette is expressed in cardiac muscle at Z-disc regions and is significantly smaller (roughly 1/6 of the size).[5] Nebulette interacts with actin, tropomyosin, alpha-actinin.[6] Xin, and XIRP2.[7]
Function
[edit | edit source]Nebulette was identified in 1995 by Moncman and Wang using primary cultures of chicken embryonic cardiomyocytes by immunoprecipitations with certain anti-nebulin monoclonal antibodies.[8] Normal expression of nebulette is essential for the assembly and contractile function of myofibrils.[9] Specifically, nebulette appears to regulate the stability and length of actin thin filaments, as well as beating frequencies of cardiomyocytes; reduction of full-length nebulette protein in cardiomyocytes resulted in reduced thin filament lengths, depressed beating frequencies and loss of thin filament regulatory proteins troponin I and tropomyosin.[10][11]
Clinical significance
[edit | edit source]Mutations in the NEBL gene have been associated with dilated cardiomyopathy.[12] Studies in transgenic mice have supported their causative role in endocardial fibroelastosis and dilated cardiomyopathy.[13]
References
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External links
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- Mass spectrometry characterization of human NEBL at COPaKB Archived 2016-03-03 at the Wayback Machine
- nebulette at the U.S. National Library of Medicine Medical Subject Headings (MeSH)