Unique Amino Acid Signatures That Are Evolutionarily Conserved Distinguish Simple-Type, Epidermal, and Hair Keratins

The study analyzed keratin sequences from various species, focusing on epidermal, simple-type epithelial, and hair keratins. It found that keratin domains have distinct amino acid compositions: hair keratins are rich in cysteines and prolines, epidermal keratins are abundant in glycine and phenylalanine but low in alanine, and simple-type epithelial keratins are enriched in acidic and basic residues. These differences are evolutionarily conserved and reflect the unique structural and functional roles of each keratin type. Additionally, cysteines and histidines, though rare, are frequently involved in de novo mutations in keratins, highlighting their significance in keratin function and mutation hotspots.