Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer of the skin are sometimes referred to as basal keratinocytes. Keratinocytes form a barrier against environmental damage by heat, UV radiation, water loss, pathogenic bacteria, fungi, parasites, and viruses. A number of structural proteins, enzymes, lipids, and antimicrobial peptides contribute to maintain the important barrier function of the skin. Keratinocytes differentiate from epidermal stem cells in the lower part of the epidermis and migrate towards the surface, finally becoming corneocytes and eventually be shed off, which happens every 40 to 56 days in humans.
Keratin 1 is a Type II intermediate filament (IFs) of the intracytoplasmatic cytoskeleton. Is co-expressed with and binds to Keratin 10, a Type I keratin, to form a coiled coil heterotypic keratin chain. Keratin 1 and Keratin 10 are specifically expressed in the spinous and granular layers of the epidermis. In contrast, basal layer keratinocytes express little to no Keratin 1. Mutations in KRT1, the gene encoding Keratin 1, have been associated with variants of the disease bullous congenital ichthyosiform erythroderma in which the palms and soles of the feet are affected. Mutations in KRT10 have also been associated with bullous congenital ichthyosiform erythroderma; however, in patients with KRT10 mutations the palms and soles are spared. This difference is likely due to Keratin 9, rather than Keratin 10, being the major binding partner of Keratin 1 in acral keratinocytes.
Transglutaminases are enzymes that in nature primarily catalyze the formation of an isopeptide bond between γ-carboxamide groups ( -(C=O)NH2 ) of glutamine residue side chains and the ε-amino groups ( -NH2 ) of lysine residue side chains with subsequent release of ammonia ( NH3 ). Lysine and glutamine residues must be bound to a peptide or a protein so that this cross-linking (between separate molecules) or intramolecular (within the same molecule) reaction can happen. Bonds formed by transglutaminase exhibit high resistance to proteolytic degradation (proteolysis). The reaction is
Protein-glutamine gamma-glutamyltransferase K is a transglutaminase enzyme that in humans is encoded by the TGM1 gene.
Keratohyalin is a protein structure found in cytoplasmic granules of the keratinocytes in the stratum granulosum of the epidermis. Keratohyalin granules (KHG) mainly consist of keratin, profilaggrin, loricrin and trichohyalin proteins which contribute to cornification or keratinization, the process of the formation of epidermal cornified cell envelope. During the keratinocyte differentiation, these granules maturate and expand in size, which leads to the conversion of keratin tonofilaments into a homogenous keratin matrix, an important step in cornification.
Cystatin-A is a protein that in humans is encoded by the CSTA gene.
Elafin, also known as peptidase inhibitor 3 or skin-derived antileukoprotease (SKALP), is a protein that in humans is encoded by the PI3 gene.
S100 calcium-binding protein A11 (S100A11) is a protein that in humans is encoded by the S100A11 gene.
Protein-glutamine gamma-glutamyltransferase E is an enzyme that in humans is encoded by the TGM3 gene.
Fatty acid-binding protein, epidermal is a protein that in humans is encoded by the FABP5 gene.
Periplakin is a protein that in humans is encoded by the PPL gene.
Small proline-rich protein 3 is a protein that in humans is encoded by the SPRR3 gene, which is found within the epidermal differentiation complex (EDC).
Loricrin is a protein that in humans is encoded by the LOR gene.
Envoplakin is a protein that in humans is encoded by the EVPL gene.
Cornifin-B is a protein that in humans is encoded by the SPRR1B gene.
Keratin, type I cuticular Ha1 is a protein that in humans is encoded by the KRT31 gene.
Cornifin-A is a protein that in humans is encoded by the SPRR1A gene.
Small proline-rich protein 2A is a protein that in humans is encoded by the SPRR2A gene.
Trichohyalin is a protein that in mammals is encoded by the TCHH gene.
The epidermal differentiation complex (EDC) is a gene complex comprising over fifty genes encoding proteins involved in the terminal differentiation and cornification of keratinocytes, the primary cell type of the epidermis. In humans, the complex is located on a 1.9 Mbp stretch within chromosome 1q21. The proteins encoded by EDC genes are closely related in terms of function, and evolutionarily they belong to three distinct gene families: the cornified envelope precursor family, the S100 protein family and the S100 fused type protein (SFTP) family.
