More than 60 previously undetected SAM domain‐containing proteins have been identified using profile searching methods. Among these are over 40 EPH‐related receptor tyrosine kinases (RPTK), Drosophila bicaudal‐C, a p53 from Loligo forbesi, and diacylglycerol‐kinase isoform δ. This extended dataset suggests that SAM is an evolutionary conserved protein binding domain that is involved in the regulation of numerous developmental processes among diverse eukaryotes. A conserved tyrosine in the SAM sequences of the EPH related RPTKs is likely to mediate cell‐cell initiated signal transduction via the binding of SH2 containing proteins to phosphotyrosine.