Unconventional myosin-XVIII A/B (MYO18A/B) belongs to class XIII myosin that contains two large domains of unknown function at the N and C-termini []. MYO18B appears to be expressed mainly in human cardiac and skeletal muscles and is involved in the regulation of muscle specific genes []. Its inactivation is involved in lung cancer progression [].Myosin constitutes a large superfamily of actin-dependent molecular motors. Myosin binds to actins and moves along actin filaments by using the energy from ATP hydrolysis. Myosin is involved in muscular contraction, cytokinesis, membrane trafficking and signal transduction [, ]. Myosins are typically composed of three functional domains:Motor head domain whose core sequence is highly conserved in all the myosin classes. This domain binds to actin and uses ATP hydrolysis to generate force to move along actin filaments. Neck domain composed of a long helix of variable length depending on the number of IQ motifs (has a consensus sequence of IQXXXRGXXXR) []. This domain acts as a linker and as a lever arm. The neck domain also serves as a binding site for moysin light chains, which are calmodulin-like proteins that have regulatory functions. Tail domain is the most diverse domain and vary in length and in sequence. Many myosin tails form coiled-coil structure that allow the molecules to dimerise and produce two-headed molecules. This domain mediates interaction with cargo molecules and/or other myosin subunits.
Many members of myosin class XVIII contain an N-terminal PDZ domain which is commonly found in proteins establishing molecular complexes. Mammals express a second isoform, Myo18B, that lacks the PDZ domain []. They also contain a motor domain which does not exhibit ATPase activity, suggesting that these myosins function as an actin tether protein [, ]. They also have two IQ domains that probably bind light chains or related calmodulins and a C-terminal tail with two sections of coiled-coil domains, which are thought to mediate homodimerization []. Myo18A has been implicated in stromal cell differentiation []and Myo18B in tumor suppression [].This entry represents the motor domain.
