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A human myopathy has been reported to be caused by a point mutation in a fast myosin heavy chain gene. This myopathy is autosomal dominant inclusion-body myopathy type3 and is caused by the mutation, which change glutamic acid into lysine at the 706th amino acid, is located at the SH1 helix region of the myosin II motor domain. The mutation in the SH1 helix is located a highly conserved region of motor domain. The SH1 helix region acts as a linker for transmitting the structural changes of ATP-binding site in the catalysis domain to the lever arm. To investigate the effect of the mutation on the actin-myosin motility, we have introduced a corresponding mutation into the SH1 helix of Dictyosterium myosin II (E683K). The mutation resulted in a decrease in the actin-myosin sliding velocity (about 1/3 of the wild type), a decrease in thermal stability and the thermal aggregation of the myosin, which might be implicated in the disease process. This suggests that SH1 helix has an important function in the motor activity and the ability to interact with F-actin is reduced.