|Symbols||; NEB177D; NEM2|
The NEBL gene encodes the protein Nebulette, a cardiac-specific isoform belonging to the nebulin family of proteins. 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.
Nebulette is a 116.4 kDa protein composed of 1014 amino acids. 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. 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. 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). Nebulette interacts with actin, tropomyosin, alpha-actinin. Xin, and XIRP2.
Nebulette was identified in 1995 by Moncman and Wang using primary cultures of chicken embryonic cardiomyocytes by immunoprecipitations with certain anti-nebulin monoclonal antibodies. Normal expression of nebulette is essential for the assembly and contractile function of myofibrils. 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.
Mutations in the NEBL gene have been associated with dilated cardiomyopathy. Studies in transgenic mice have supported their causative role in endocardial fibroelastosis and dilated cardiomyopathy.
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- Moncman CL, Wang K (Feb 2002). "Targeted disruption of nebulette protein expression alters cardiac myofibril assembly and function". Experimental Cell Research 273 (2): 204–18. PMID 11822876. doi:10.1006/excr.2001.5423.
- Bonzo JR, Norris AA, Esham M, Moncman CL (Nov 2008). "The nebulette repeat domain is necessary for proper maintenance of tropomyosin with the cardiac sarcomere". Experimental Cell Research 314 (19). PMID 18823973. doi:10.1016/j.yexcr.2008.09.001.
- Moncman CL, Wang K (Feb 2002). "Targeted disruption of nebulette protein expression alters cardiac myofibril assembly and function". Experimental Cell Research 273 (2). PMID 11822876. doi:10.1006/excr.2001.5423.
- Arimura T, Nakamura T, Hiroi S, Satoh M, Takahashi M, Ohbuchi N et al. (Nov 2000). "Characterization of the human nebulette gene: a polymorphism in an actin-binding motif is associated with nonfamilial idiopathic dilated cardiomyopathy". Human Genetics 107 (5). PMID 11140941.
- Purevjav E, Varela J, Morgado M, Kearney DL, Li H, Taylor MD et al. (Oct 2010). "Nebulette mutations are associated with dilated cardiomyopathy and endocardial fibroelastosis". Journal of the American College of Cardiology 56 (18). PMID 20951326. doi:10.1016/j.jacc.2010.05.045.
- Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS et al. (Oct 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9). PMID 23965338. doi:10.1161/CIRCRESAHA.113.301151.
- Mass spectrometry characterization of human NEBL at COPaKB
- nebulette at the US National Library of Medicine Medical Subject Headings (MeSH)