The nebulin-like motif or nebulin repeat is a tandemly repeated actin-binding module of about 35 amino acids. The repeat is named after the nebulin protein, which is a large protein specific for vertebrate skeletal muscle that may regulate the length of thin filaments. Nebulin contains about 185 copies of the repeat and those in the central part of nebulin are organized into seven-module super-repeats, which seems to reflect an interaction with tropomysin/troponin [1]. Nebulin repeats occur in metazoan actin-binding proteins, most of which are specific for muscle tissues. Most nebulin repeat proteins contain a C-terminal SH3 domain (see <PDOC50002>) and/or a N-terminal LIM zinc-binding domain (see <PDOC00382>). The repeats in nebulin and nebulette bind filamentous actin (F-actin) and may also associate with tropomyosin and troponin. The nebulin repeat has a predicted α-helical secondary structure and contains a central conserved SXXXY motif [1,2,3].

Some proteins known to contain nebulin repeats:

• Vertebrate nebulin, which is specifically found in skeletal muscle, where it is involved in maintaining the structural integrity of the sarcomeres.
• Vertebrate nebulette, a nebulin-like protein that is specifically expressed in cardiac muscle, where it interacts with actin filaments.
• Human LASP-1 (LIM and SH3 protein-1), a cytoskeletal protein that is ubiquitously expressed in most cell types and may play a role in the regulation of the actin cytoskeleton. LASP-1 is conserved among metazoans.
• Mammalian nebulin-related anchoring protein (NRAP), which occurs in both skeletal muscle and heart and appears to be involved in anchoring the actin filaments to the sarcolemma.

The profile we developed covers the entire nebulin repeat.