Recently, we have identified a new protein (DA41) which can associate with candidate tumor-suppressor DAN protein. In the present study, we have searched for DA41-interacting protein(s), using a yeast two-hybrid system. An adult rat lung cDNA library was screened by using a truncated form of DA41 (1-308) which lacks a DAN-binding region as bait. One of the positive clones, T16, contained a cDNA sequence of 1934 nucleotides with a single open reading frame of 493 amino acids. A data base search revealed that T16 exhibited a strong sequence similarity to the human epidermal growth factor (EGF)-like protein, S(1-5). The region encoding amino acids 155-232 of DA41 was identified for the interaction with T16. Since DAN and S(1-5) proteins are known to suppress and stimulate DNA synthesis, respectively, it is possible that functional interaction of DAN with S(1-5) through DA41 might play an important role(s) in the regulation of cell growth.