The Molecular Revolution in Cutaneous Biology: Keratin Genes and their Associated Disease: Diversity, Opportunities, and Challenges  Pierre A. Coulombe  Journal of Investigative Dermatology  Volume 137, Issue 5, Pages e67-e71 (May 2017) DOI: 10.1016/j.jid.2016.04.039 Copyright © 2016 The Author Terms and Conditions

Figure 1 The origin of the Moll catalog for human keratin proteins. Cytoskeletal proteins from various human epithelia, carcinomas and cultured epithelial cells were separated by two-dimensional gel electrophoresis. Cytokeratin polypeptides detected and identified by antibody binding in immunoblot experiments, and in most cases also by peptide mapping, are arranged according to their mobilities in these gel electrophoretic systems. X axis: isoelectric pH values for molecules denatured in 9.5 mol/L urea (data combined from isoelectric focusing and nonequilibrium pH gradient electrophoresis). Y axis: relative molecular weight, as determined by SDS-PAGE. Cytokeratin polypeptides are designated by Arabic numerals. Horizontal series of spots indicate different isoelectric variants of the same polypeptide. Large dots indicate the specific major variant, usually the most basic, nonphosphorylated one. Small dots indicate minor variants. Open circles indicate variants of the specific polypeptide not always found in analyses from various cell types. A, rabbit actin; BSA, bovine serum albumin; Mr, molecular mass; PGK, 3-phosphoglycerokinase; V, human vimentin. Figure and legend reproduced from (Moll et al., 1982) with permission. Journal of Investigative Dermatology 2017 137, e67-e71DOI: (10.1016/j.jid.2016.04.039) Copyright © 2016 The Author Terms and Conditions

Figure 2 Human keratin phylogenic tree, postgenomics. (a) Comparison of the primary structure of human keratins using publicly available ClustalW and TreeView softwares. Sequence relatedness is inversely correlated with the length of the lines connecting the various sequences as well as the number and position of branch points. This comparison makes use of the sequences from the head and central rod domain for each keratin. Two major branches are seen in this tree, corresponding exactly to the known partitioning of keratin genes into type I and type II sequences. Beyond this dichotomy, each subtype is further segregated into major subgroupings. (b) Location and organization of type I and type II keratin genes in the human genome. All functional type I keratin genes, except KRT18 are clustered on the long arm of human chromosome 17, and all functional type II keratin genes are located on the long arm of chromosome 12. KRT18, a type I gene, is located at the telomeric boundary of the type II gene cluster. The suffix P identifies keratin pseudogenes. As highlighted by the color code used in frames a and b, individual type I and type II keratin genes belonging to the same subgroup, on the basis of the primary structure of their protein products, tend to be clustered in the genome. Moreover, highly homologous keratin proteins (e.g., K5 and K6 paralogs; also K14, K16, and K17) are often encoded by neighboring genes, pointing to the key role of gene duplication in generating keratin diversity. These features are virtually identical in mice (not shown). This figure is adapted from Coulombe et al., 2013 with permission. Journal of Investigative Dermatology 2017 137, e67-e71DOI: (10.1016/j.jid.2016.04.039) Copyright © 2016 The Author Terms and Conditions