Recently a novel nuclear protein mainly expressed in S and G2 phase cells was characterized using autoantibodies from a cancer patient (Exp. Cell Res., 212, 255-261, 1994). cDNA clones were isolated by immunoscreening, and sequence analysis revealed that the cDNA clones encoded a 713-amino acid residue polypeptide which is provisionally named SG2NA (S/G2 nuclear antigen). In the carboxyl terminal half of SG2NA, there are 6 copies of WD-40 motifs characteristic of a large family of proteins of which the prototype is beta-transducin/enhancer of split (TLE). In addition, there are nuclear localization sequence and phosphorylation sites related to the TLE proteins. Autoantibodies occurring spontaneously in certain cancer patients have been useful reagents for identifying cellular proteins and this is the first report of a novel WD-40 protein which is the target of an autoimmune response.