Deiodinases share an evolutionarily conserved thyroid hormone-binding motif.

Human and animal thyroid hormone (TH) plasma carriers (THPC, n=426), cell surface TH transporters (CSTT, n=8,691), and TH nuclear receptors (TR, n=624) share a 49-position long TH-binding motif. Particularly conserved are positions 22-26, where a 5-residue TH-binding motif was originally detected. We extended our research to the 488 sequences of human and animal selenodeiodinases (dio-1, dio-2, dio-3).  In the 10,229 sequences (THPC+CSTT+TR+deiodinases), 15/49 positions are very highly and another 18/49 highly conserved. The very highly conserved 5-residue core TH-binding motif is now W/F/Y, L/I/V/M, I/V/M/L, P, L/V/I/M. Concerning deiodinases, of the 13 conserved residues in their active centers (F121-E214, F128-E228, F139-E233), 11 (dio-1/dio-3) or 10 (dio-2) fall within the 49-position motif. Conserved in the consensus from THPC, CSTT and TR are F129/F136/F147 (position 11). Other matches of deiodinases concerned the nonapolipoprotein THPC: of particular interest, P135/P146 (dio-2/dio-3; position 9), E155/D162/E173 (position 28), S160/S167/S178 (position 33), W163/W170/W178 (position 36). The shared TH-binding domain, which is likely the product of an ancestor gene, may explain why diverse plasma and cell-associated proteins interact with TH.