Regulation of the NUE in thyroid cells. A. Map of the human chromosome 19p around the NIS gene locus. The “A” in the translation start site (ATG) of NIS is referred to as +1. B. TSHR signaling pathways to NUE. NIS expression in thyroid cells is predominantly regulated by the TSHR signaling to NUE. Gain-of-function studies of the molecules, indicated by red color, have demonstrated stimulation of the NUE activity. The consensus sequences of cis-elements of PAX8, CRE, and USF1 are indicated along with the sequence of human NUE. *, Stimulatory effects have been reported with rat NUE, which contains an additional Pax8 element and an NFκB element (Nicola et al., 2010). AC, adenylyl cyclase; Ref-1, apurinic apyrimidinic endonuclease redox effector factor-1.