A cDNA encoding the human homologue of the murine DTK receptor tyrosine kinase has been isolated from a human brain library. The DTK cDNA encodes a mature protein of 850 amino acids with similar structural features to those of the murine receptor. The extracellular domain contains two immunoglobulin-like motifs and two fibronectin type III modules; features which define a new class of receptor tyrosine kinase. The human DTK gene has been mapped by fluorescent in situ hybridization to chromosome 15q15, and a DTK-related gene identified at chromosome 15q24. In fetal tissues, transcripts for DTK were detected in brain, kidney, lung and heart. Prominent expression was observed in the embryonal carcinoma cell line NT2/D1. Expression of the gene is up-regulated in adult tissues with high levels of expression in many regions of the adult brain. DTK is also abundantly expressed in adult kidney, testis, and ovary.