We have isolated cDNA clones encoding the complete sequence of the heavy chain of tissue factor (TF), the high-affinity receptor responsible for cellular initiation of the coagulation protease cascade. An 885 bp open reading frame encodes a 295 amino acid polypeptide including a leader sequence with alternative cleavage sites. A single 2.3 kb mRNA is identified, and Southern blotting is consistent with a single gene. The coding sequence defines a protein with features characteristic of an integral membrane protein. This receptor appears novel, lacking significant homology with other proteins; however, TF contains the uncommon tryptophan-lysine-serine(WKS) sequence repeated three times, a sequence we find in some serine protease-binding proteins and suggest may represent a functional sequence motif.