Evolutionary conservation of the Adaptive Domain in nesprin-1 and nesprin-2. (A) Amino acid sequence of the AD of nesprin-1 and nesprin-2 from human, mouse, Bos taurus, chicken and Zebrafish (residues 558-786 in human nesprin-1 isoform, AF444779). Overlines indicate left and right halves of the putative ‘divided LEM-like domain’.8 Underlines in human nesprin-1 indicate ‘Hot loops’ (high mobility) predicted by DisEMBL. The V729L mutation (boxed) causes Emery-Dreifuss muscular dystrophy.21 (B) Schematic diagrams to scale, showing the relative positions of the ‘divided LEM-like domain in nesprin-1α8, disordered regions predicted by the ‘loops/coils’ definition (DisEMBL), disordered regions predicted by the ‘hot-loops’ definition (DisEMBL), and secondary possible structure (predicted by PSIPRED). Star highlights residue V729.