Summary
The COOH termini of Sis1 and Ydj1 share overlapping essential roles. In addition, the J domain of Ydj1 may substitute for the J domain of Sis1 (Yan and Craig 1999). In contrast, the essential function of the G/F region of Sis1 cannot be replaced by the G/F region of Ydj1 (Yan and Craig 1999), indicating a unique role of the Sis1 G/F region. Although the substrate binding domains of Sis1 and Ydj1 can substitute for one another under some conditions, they share only 29% sequence identity, compared with 66% sequence identity between the J domains. This difference likely results in some differences in substrate specificity, which may be responsible for the temperature-sensitive phenotype observed in the absence of the substrate-binding region of either Ydj1 or Sis1. Further studies will be needed to understand the specificity of Hsp40 interactions with Hsp70.