A cloned-5 kb cDNA (human placenta) contains the coding sequences for the insulin receptor. The nucleotide sequence predicts a 1382 amino acid precursor. The (I subunit comprises the N-terminal portion of the precursor and contains a striking cysteine-rich tress-linking” domain. The/I-subunit (the C-terminal portion of the precursor) contains a transmembrane domain and, in the intracellular region, the elements of a tyrosine phosphokinase: an ATP-binding site and a possible tyrosine autophosphorylation site or sites. The overall structure Is reminiscent of the EGF recep tor; the cross-linking domain of the (I subunit and several regions of the fi subunit exhibit sequence homology with the EGF receptor. The phosphoklnase domain also exhibits homology with some oncogenic proteins that have tyrosine phosphokinase activity, in particular, a striking homology with wros. Southern blotting experiments suggest that the coding region spans more than 45 kb. The insulin receptor gene is located on chromosome 19.