AUTOIMMUNITY IN STIFF-MAN SYNDROME WITH BREAST-CANCER IS TARGETED TO THE C-TERMINAL REGION OF HUMAN AMPHIPHYSIN, A PROTEIN SIMILAR TO THE YEAST PROTEINS, RVS167 AND RVS161

Amphiphysin, a neuronal protein first identified in chicken synaptic membranes, is the autoantigen of Stiff-Man Syndrome (SMS) associated with breast cancer. We have now cloned human amphiphysin and found the N- and C-terminal domains of the protein to be highly conserved between chicken and human. Patient autoantibodies have a distinct pattern of reactivity with amphiphysin, and the dominant autoepitope is located in its C-terminal region, which contains an SH3 domain. Portions of chicken and human amphiphysin are also homologous to portions of Rvs167 and Rvs161, two yeast proteins which are involved in cell entry into stationary phase upon exposure to unfavourable growth conditions.