Nebulin

Nebulin
Solution structure of the SH3 domain from human nebulin.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1ARK, 1NEB
Identifiers
Symbols	NEB ; NEB177D; NEM2
External IDs	OMIM: 161650 HomoloGene: 136285 GeneCards: NEB Gene
Gene ontology Molecular function • actin binding • protein binding • structural constituent of muscle Cellular component • cytosol • actin cytoskeleton • Z disc • extracellular vesicular exosome Biological process • muscle organ development • somatic muscle development • muscle filament sliding • regulation of actin filament length Sources: Amigo / QuickGO
Orthologs
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. 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.

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

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

Structure

The structure of the SH3 domain of nebulin was determined by NMR. 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

As of 2007, two knockout mouse models for nebulin have been developed to better understand its in vivo function. Bang and colleagues 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 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.

External links

• nebulin at the US National Library of Medicine Medical Subject Headings (MeSH)
• GeneReviews/NCBI/NIH/UW entry on Nemaline Myopathy