We have identified a breast carcinoma tyrosine phosphoprotein, discoidin domain receptor (DDR), that defines an unusual class of receptor tyrosine kinases. The DDR cDNA predicts a C-terminal tyrosine kinase domain and an N-terminal domain similar to the Dictyostelium discoideum lectin discoidin I. These domains are connected by an extraordinary hydrophilic proline/glycine-rich domain, which is interrupted by a predicted transmembrane sequence. This extended proline/glycine-rich region may be required for an unusual geometry of interaction with ligand or substrates. Discoidin I domains are also found in other proteins, including coagulation factors V and VIII, and may represent a class of domains that interact with specific cell surface molecules.