Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3). The synthesis of T3 and T4 involves iodination of selected tyrosine residues of TG/thyroglobulin followed by their oxidative coupling. Following TG re-internalization and lysosomal-mediated proteolysis, T3 and T4 are released from the polypeptide backbone leading to their secretion into the bloodstream. One dimer produces 7 thyroid hormone molecules.
Post-translational: Iodinated on tyrosine residues by TPO. There are 4 pairs of iodinated tyrosines used for coupling: acceptor Tyr-24 is coupled to donor Tyr-149 or Tyr-234, acceptor Tyr-2574 is coupled to donor Tyr-2541, acceptor Tyr-2767 in monomer 1 is coupled to donor Tyr-2767 in monomer 2 and acceptor Tyr-1310 in monomer 1 is coupled to donor Tyr-108 in monomer 2. Sulfated tyrosines are desulfated during iodination. Undergoes sequential proteolysis by cathepsins to release thyroxine (T4) and triiodothyronine (T3) hormones. In the thyroid follicle lumen, cross-linked TG (storage form) is solubilized by limited proteolysis mediated by cathepsins CTSB and/or CTSL. Partially cleaved TG is further processed by CTSK/cathepsin K and/or CTSL resulting in the release of T4. Following endocytosis, further processing occurs leading to the release of T3 and more T4 hormones.