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.
^PDB: 1NEB ; Politou AS, Millevoi S, Gautel M, Kolmerer B, Pastore A (February 1998). "SH3 in muscles: solution structure of the SH3 domain from nebulin". J. Mol. Biol.276 (1): 189–202. doi:10.1006/jmbi.1997.1521. PMID9514727.
^"Nebulette". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
^Moncman CL, Wang K (1995). "Nebulette: a 107 kD nebulin-like protein in cardiac muscle". Cell Motility and the Cytoskeleton32 (3): 205–25. doi:10.1002/cm.970320305. PMID8581976.
^Moncman CL, Wang K (Feb 2002). "Targeted disruption of nebulette protein expression alters cardiac myofibril assembly and function". Experimental Cell Research273 (2): 204–18. doi:10.1006/excr.2001.5423. PMID11822876.
^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 Research314 (19). doi:10.1016/j.yexcr.2008.09.001. PMID18823973.
^Moncman CL, Wang K (Feb 2002). "Targeted disruption of nebulette protein expression alters cardiac myofibril assembly and function". Experimental Cell Research273 (2). doi:10.1006/excr.2001.5423. PMID11822876.
^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 Genetics107 (5). PMID11140941.
^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 Cardiology56 (18). doi:10.1016/j.jacc.2010.05.045. PMID20951326.
^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 Research113 (9). doi:10.1161/CIRCRESAHA.113.301151. PMID23965338.