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Abstract

The complete primary structure of the protein product of the proto−oncogene c−mil was deduced from the nucleotide sequence of chicken c−mil cDNA clones. The c−mil protein contains 647 amino acid residues and has a calculated molecular weight of 73,132. Based on sequence comparisons with proteins of known or presumed biochemical function, two domains were recognized on the c−mil protein. In the carboxyl−terminal half of the protein, a 250−amino acid segment displays significant homology to the protein kinase domains of the src oncogene protein or of protein kinase C. In the amino−terminal half, a cysteine−rich segment (Cys−X2−Cys−X9−Cys−X2−Cys−X7−Cys−X7−Cys) of the c−mil protein shares significant homology with two similar repetitive domains of protein kinase C. Of the two structural and presumably functional domains of the c−mil protein, only the kinase domain is contained within the carboxyl−terminal 379−amino acid polypeptide encoded by the transduced v−mil allele of avian oncogenic retrovirus MH2. Hence, truncation of the 5' coding region in the course of the transduction and the resulting lack of the authentic amino−terminal domain in the protein product of the transduced allele may be a critical event in changing mil function from physiologic to oncogenic