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Solution structure of the SH3 domain from human nebulin.[1]
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols NEB ; NEB177D; NEM2
External IDs OMIM161650 HomoloGene136285 GeneCards: NEB Gene
Species Human Mouse
Entrez 4703 17996
Ensembl ENSG00000183091 ENSMUSG00000026950
UniProt P20929 n/a
RefSeq (mRNA) NM_001164507 NM_010889
RefSeq (protein) NP_001157979 NP_035019
Location (UCSC) Chr 2:
151.49 – 151.73 Mb
Chr 2:
52.14 – 52.34 Mb
PubMed search [1] [2]

Nebulin is an actin-binding protein which is localized to the thin filament of the sarcomeres in skeletal muscle. It is a very large protein (600-900 kDa) and binds as many as 200 actin monomers. Because its length is proportional to thin filament length, it is believed that nebulin acts as a thin filament "ruler" and regulates thin filament length during sarcomere assembly.[2] Other functions of nebulin, such as a role in cell signaling, remain uncertain.

Nebulin has also been shown to regulate actin-myosin interactions by inhibiting ATPase activity in a calcium-calmodulin sensitive manner.[3]

Mutations in nebulin cause some cases of the autosomal recessive disorder nemaline myopathy.[4]

A smaller member of the nebulin protein family termed nebulette, is expressed in cardiac muscle.


The structure of the SH3 domain of nebulin was determined by NMR.[1] The SH3 domain from nebulin is composed of 60 amino acid residues, of which 30 percent is in the beta sheet secondary structure (7 strands; 18 residues).

Knockout phenotype[edit]

As of 2007, two knockout mouse models for nebulin have been developed to better understand its in vivo function. Bang and colleagues[5] demonstrated that nebulin-knockout mice die postnatally, have reduced thin filament length, and impaired contractile function. Postnatal sarcomere disorganization and degeneration occurred rapidly in these mice, indicating the nebulin is essential for maintaining the structural integrity of myofibrils. Witt and colleagues[6] had similar results in their mice, which also died postnatally with reduced thin filament length and contractile function. These nebulin-knockout mice are being investigated as animal models of nemaline myopathy.


  1. ^ a b 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. PMID 9514727. 
  2. ^ McElhinny AS, Kazmierski ST, Labeit S, Gregorio CC (Jul 2003). "Nebulin: the nebulous, multifunctional giant of striated muscle". Trends in Cardiovascular Medicine 13 (5): 195–201. doi:10.1016/S1050-1738(03)00076-8. PMID 12837582. 
  3. ^ Root DD, Wang K (Oct 1994). "Calmodulin-sensitive interaction of human nebulin fragments with actin and myosin". Biochemistry 33 (42): 12581–91. doi:10.1021/bi00208a008. PMID 7918483. 
  4. ^ Pelin K, Hilpelä P, Donner K, Sewry C, Akkari PA, Wilton SD et al. (Mar 1999). "Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy". Proceedings of the National Academy of Sciences of the United States of America 96 (5): 2305–10. doi:10.1073/pnas.96.5.2305. PMC 26779. PMID 10051637. 
  5. ^ Bang ML, Li X, Littlefield R, Bremner S, Thor A, Knowlton KU et al. (Jun 2006). "Nebulin-deficient mice exhibit shorter thin filament lengths and reduced contractile function in skeletal muscle". The Journal of Cell Biology 173 (6): 905–16. doi:10.1083/jcb.200603119. PMC 2063916. PMID 16769824. 
  6. ^ Witt CC, Burkart C, Labeit D, McNabb M, Wu Y, Granzier H et al. (Aug 2006). "Nebulin regulates thin filament length, contractility, and Z-disk structure in vivo". The EMBO Journal 25 (16): 3843–55. doi:10.1038/sj.emboj.7601242. PMC 1553189. PMID 16902413. 

Further reading[edit]

  • Björklund AK, Light S, Sagit R, Elofsson A (Sep 2010). "Nebulin: a study of protein repeat evolution". Journal of Molecular Biology 402 (1): 38–51. doi:10.1016/j.jmb.2010.07.011. PMID 20643138. 

External links[edit]