Fig. 2

K8 K393R and K18 D89H are the first identified simple epithelial keratin variants located in the most conserved regions of the rod domain. Conservation of the novel K8 K393R/K18 D89H variants among (a,c) species and b type II or d type I keratins (standard single-letter amino acid abbreviations are used). Sequences surrounding the novel K8/K18 variants are depicted. Dots highlight conserved amino acids. e Distribution of simple epithelial and epidermal keratin variants within the keratin backbone. The schematic shows the characteristic tripartite structure (N-terminal ‘head’, central ‘rod’ and C-terminal ‘tail’ domains) of all IFs including keratins. The rod domain is subdivided into IA, IB, IIA, and IIB subdomains that in turn are separated through linker (L1, L1-2, L2) sequences. The shaded regions are the most conserved segments of the rod domain (termed helix initiation motif ‘HIM’ and helix termination motif ‘HTM’) and constitute mutation ‘hot spots’ in severe epidermal keratins and other IF mutations. Note that unlike epidermal keratins, the frequent human K8/K18 variants are located outside HIM/HTM. IF, intermediate filament