Proteins in this family contains Xin repeats, which define anactin-binding motif. In humans two Xin-repeat proteins have been identified, XIRP1 and XIRP2. They are expressed during early developmental stages of cardiac and skeletal muscles []and have an important role in cardiac development and function []. They bind to and stabilise F-actin [].This entry represents XIRP2, also known as Xin-beta. In mouse, it initiates the maturation of the intercalated discs (ICDs)during postnatal heart development [].
Nebulin is a giant filamentous protein (600-900 kD) that plays a role in numerous cellular processes including regulation of muscle contraction, Z-disc formation, and myofibril organization and assembly in skeletal muscle. It contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. The N terminus of nebulin is located near the pointed end of the thin filament and contains a binding site for the actin filament capping protein tropomodulin (Tmod). The super repeat region of nebulin has been shown to interact with kelch-like family member 40 (KLHL40). The C terminus of nebulin is located within the highly specialized boundary of the sarcomere (Z-disc), and plays an important role in myofibril assembly, mechanosensing, signaling, force generation and transmission, and sarcolemmal resilience. The SH3 domain of nebulin interacts with multiple proteins, such as alpha-actinin, XIRP2 and titin []. Mutations in nebulin can cause nemaline myopathy, characterised by muscle weakness which can be severe and can lead to neonatal lethality []. This entry represents the SH3 domain of Nebulin.
This entry include nebulin and nebulin-related-anchoring protein (N-RAP). Nebulin is a giant filamentous protein (600-900 kD) that plays a role in numerous cellular processes including regulation of muscle contraction, Z-disc formation, and myofibril organization and assembly in skeletal muscle. It contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. The N terminus of nebulin is located near the pointed end of the thin filament and contains a binding site for the actin filament capping protein tropomodulin (Tmod). The super repeat region of nebulin has been shown to interact with kelch-like family member 40 (KLHL40). The C terminus of nebulin is located within the highly specialized boundary of the sarcomere (Z-disc), and plays an important role in myofibril assembly, mechanosensing, signaling, force generation and transmission, and sarcolemmal resilience. The SH3 domain of nebulin interacts with multiple proteins, such as alpha-actinin, XIRP2 and titin []. Mutations in nebulin can cause nemaline myopathy, characterised by muscle weakness which can be severe and can lead to neonatal lethality []. Nebulin-related-anchoring protein (N-RAP) is a muscle-specific protein that may serve as a scaffold for premyofibril assembly [, ]. N-RAP contains a N-terminal LIM domain (LIM), the C-terminal actin-binding nebulin super repeats and the nebulin-related simple repeats (IB) in between the two []. The N-terminal IB region is essential for alpha-actinin organisation, while the N-RAP super repeats are essential for sarcomeric actin organisation [].
