Journal of Molecular Endocrinology

Schematic diagrams of mouse and human GLIS3 gene and protein structures. (A) Mouse Glis3 gene and protein structures. The full-length mouse Glis3 gene contains 11 exons and encodes a protein of 935 aa. The ZFD is encoded by part of exon 4 and is responsible for the binding to the consensus GLIS3RE of its target genes such as insulin, Ngn3 and Ccnd2. TAD is localized at its C-terminus. CUL3 and ITCH promote GLIS3 polyubiquitination and degradation via the proteasomal pathway. SUFU, interacting with GLIS3 through the conserved VYGHF motif at N-terminus of GLIS3, was shown to inhibit the association of CUL3 with GLIS3, thereby protecting GLIS3 protein from proteolytic degradation. (B) Human GLIS3 gene and protein structures. Human GLIS3 gene have two major variants that encode GLIS3 protein isoforms a and b that share the last 9 exons. The variant 1 encodes the longest isoform a with 930 aa. The variant 2 harbors a distinct 5′ UTR and lacks an in-frame portion of the 5′ coding region, resulting in a shorter N-terminus in isoform b with 775 aa, compared to variant 1.