We previously identified a novel protein tyrosine kinase gene, tyk2, by screening a human lymphoid cDNA library with a tyrosine kinase domain specific c-fms restriction fragment under low stringency hybridization conditions. We have now isolated and sequenced a full length tyk2 cDNA clone; demonstrated that this gene is widely expressed in hematopoietic and non-hematopoietic cell lines; and mapped it to chromosome 19p13. 2. The cDNA clone is 4176 nucleotides long and codes for a putative protein with a molecular weight of 134 kilodaltons. Hydrophobicity analysis of our sequence does not identify a transmembrane domain, which is found in all members of the receptor class of protein tyrosine kinases; nor can we detect an SH2 domain, found in all previously identified non-receptor protein kinases. We therefore propose that tyk2 is the prototype of a new class of non-receptor protein tyrosine kinases.