Thyroid hormone receptors (TR), also known as c-erbA-2, are ligand-dependent, intracellular proteins that stimulate transcription of specific genes by binding to specific DNA sequences called hormone response elements following activation by the appropriate hormone. Thyroid hormones, through their interaction with TR, effect metabolic processes, growth and development in many tissues by regulating the expression of genes for growth hormone, malic enzyme and several hepatic proteins. There are two forms of TR; TR alpha (on chromosome 17) and TR beta (on chromosome 3). Each of these isoforms also has two isoforms; TR alpha-1 and TRv alpha-2, and TR beta-1 and TR beta-2 respectively. TR alpha-1 and 2 are identical through amino acid 370 where their sequences diverge. TRv alpha-2, which does not bind T3 and is a strong negative regulator of the functional TR, is 80 amino acids longer than TR alpha-1. The corresponding gene for the thyroid hormone receptor beta-1 is NR1A2.
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