A Pleiotropic Role for the Orphan Nuclear Receptor Small Heterodimer Partner in Lipid Homeostasis and Metabolic Pathways

Figure 1

Top: the genomic structure of human SHP. Rectangles represent the two exons with a single intron spanning approximately 1.8 kilobases and located on a single locus on chromosome 1p36.1 [18]. The region 5′ includes ≈600 nucleotides from the transcription start site and is characterized by promoter activity. Bottom: typical nuclear receptor is compared with the domain structure of human SHP. The canonical structure of NR includes the N-terminal activation function 1 (AF1) domain, DNA-binding domain (DBD), ligand-binding domain (LBD), and C-terminal activation function 2 (AF2) domain. SHP lacks the DBD. Two functional LXXLL-related motifs (also named as NR boxes) are typical of the human SHP structural domains. Such motifs are located in the putative N-terminal helix 1 of the LBD and in the C-terminal region of the helix 5. While active NRs exhibit glutamic acid in AF-2, the SHP AF-2 domain is replaced with aspartic acid. Adapted from Chanda et al. [15] and Shulman and Mangelsdorf [130].