Thyroid hormone-interacting cell and plasma proteins share a common motif

We hypothesized that a thyroid hormone (TH)-binding consensus sequence, which is shared by human and animal TH plasma carriers (THPC), might also be shared by cell surface TH transporters (CMTTH) and TH nuclear receptors (THR). We generated the consensus for CMTTH or THR from 8,691 or 624 sequences. In the 49 position-long THPC consensus, eight positions were occupied by very highly conserved (>50% of sequences) and 11 by highly conserved (>33-50% of sequences) groups of residues. Matches between very highly conserved residues of the same group were seven, five or nine when comparing CMTTH vs THPC, THR vs THPC or THR vs CMTTH. Matches between highly conserved residues of the same group were found at one position when comparing CMTTH vs THPC. Noteworthy, the 5-residue TH-binding motif (Y,L/I/M,X,X,V/L/I) originally detected in a few THPC and then confirmed in the 426 THPC (Y/F/W,L/V/I/M,L/V/M/I,l/v/i/m,V/L/I/M) at positions 22-26, was also confirmed in the total 9,741 sequences (W/F/Y,L/I/V/M,I/V/M/L,P,L/V/I/M). In conclusion, proteins so genetically and functionally diverse share TH binding because they share a homologous region that remains conserved phylogenetically.