Keratin 5

Keratin 5, like other members of the keratin family, is an intermediate filament protein. These polypeptides are characterized by a 310 residue central rod domain that consists of four alpha helix segments (helix 1A, 1B, 2A, and 2B) connected by three short linker regions (L1, L1-2, and L2). Lying on either side of the central rod are variable, non-helical head and tail regions which protrude from the IF surface and provide specificity to different IF polypeptides. The coiled-coil dimers undergo stepwise assembly and combine in an antiparallel manner, forming end-to-end interactions with other coiled-coils to form large 10 nm intermediate filaments. == Function ==

Keratin 5 (and K14) are expressed primarily in basal keratinocytes in the epidermis, specifically in the stratified epithelium lining the skin and digestive tract. K5/K14 keratin pairs are able to undergo extensive bundling due to the non-helical tail of K15 acting as a weak cross-linker at the intermediate filament surface. This bundling increases the elasticity, and therefore the mechanical resilience, of the intermediate filaments. At the hemidesmosome, plectin and BPAG1 associate with transmembrane proteins α6β4 integrin, a type of cell adhesion molecule, and BP180/collagen XVII, linking K5/K14 filaments in the basal cells to the basal lamina. == Clinical relevance ==

Epidermolysis bullosa simplex Epidermolysis bullosa simplex (EBS) is an inherited skin blistering disorder associated with mutations in either K5 or K14. EBS-causing mutations are primarily missense mutations, but a small number of cases arise from insertions or deletions. Their mechanism of action is dominant negative interference, with the mutated keratin proteins interfering with the structure and integrity of the cytoskeleton. Basal-like breast cancers tend to have poorer outcomes than other types of breast cancer due to a lack of targeted therapies. These breast cancers do not express human epidermal growth factor receptor-2 or receptors for estrogen or progesterone, making them immune to Trastuzumab/Herceptin and hormonal therapies, which are very effective against other breast cancer types. Due to the fact that K5 expression is only seen in basal cells, it serves as an important biomarker for screening patients with basal-like breast cancers to ensure that they are not receiving ineffective treatment. Similarly, it can be used to distinguish papilloma, which is positive for K5, from papillary carcinoma, which is K5 negative. It can also serve as a marker of basal cell carcinoma, transitional cell carcinoma, salivary gland tumors, and thymoma. == See also ==