A Novel Thyroid Hormone Receptor Encoded by a cDNA Clone from a Human Testis Library

The c-erbA gene belongs to a multigene family that encodes transcriptional regulatory proteins including the v-erbA oncogene product, steroid hormone receptors, and the vitamin D₃ receptor. A v-erbA DNA probe encoding the DNA-binding region of the v-erbA protein was used to screen a human complementary DNA testis library. One of the clones isolated, erbA-T-1, was found to encode a 490-amino acid protein (erbA-T). The erbA-T polypeptide shows high homology with the proteins encoded by both the chicken c-erbA and the human c-erbA-β genes but is most closely related to the chicken gene. The chicken c-erbA and the human c-erbA-β genes encode high-affinity receptors for thyroid hormone, and here it is shown that the erbA-T protein binds specifically to 3,5,3'-triiodo-L-thyronine with a dissociation constant of 3.8 ± 0.2 × 10^-10M. These data imply that more than one thyroid hormone receptor exists in humans and that these receptors might have different tissue- and gene-activating specificities.