Trichohyalin is a protein that in mammals is encoded by the TCHH gene.
Discovery
In 1903 the name “trichohyalin” was assigned to the granules of the inner root sheath of hair follicles discovered by H. Voerner. In 1986 the name was reassigned to a protein isolated from sheep wool follicles.
Gene location
The human TCHH is located on the long arm of chromosome 1 at region 2band 1 sub-band 3, from base pair 152,105,403 to base pair 152,116,368. This region in chromosome 1q21 is known as the epidermal differentiation complex, since it harbors over fifty other genes involved in keratinocyte differentiation. Gene coding sequence contains 5829 nucleotides. Gene orthologs were identified in most mammals including mice, chickens, rats, pigs, sheep, horses and other species.
The protein forms frequent links between the heads and tails of the keratin chains and, thus, participates in keratin intermediate filaments inter-filamentous cross-linking. It also carries a function of a major reinforcement cross-bridging protein for the cell envelope barrier structure of the IRS and participates in coordination of CE structure. Overall, trichohyalin confers mechanical strength to the hair follicle inner root sheath and to other toughened epithelial tissues.
Structure
Trichohyalin belongs to the S100-fusedprotein family. It is a monomer, containing 1943 amino acids, and has elongated single-stranded alpha-helical conformation based on its unusually high content of charged residues. Molecular mass of the human trichohyalin is 253925 Da. The protein includes nine domains. Domain 1 contains two EF-hand calcium-binding domains. Domains 2-4, 6, and 8 are almost entirely alpha-helical, configured as a series of peptide repeats of varying regularity, and are thought to form a single-stranded alpha-helical rod stabilised by ionic interactions. Domain 6 is the most regular and may bind KIF directly by ionic interactions. Domains 5 and 7 are less well organised and may induce folds in the molecule. Domain 9 contains the C-terminus, conserved among different species.
TCHH protein is extensively cross-linked to itself in the IRS tissue as well as to keratin intermediate filaments. All TCHH-keratin links involved only domain 6 or 8 sequences. The protein can also form cross-links to all other CE proteins including involucrin, envoplakin, keratin, repetin, desmoplakin, SPR1, SPR2, and LEP. TCHH-TCHH and TCHH-CE protein links are distributed among domains 2–5, but are uncommon in domains 6 and 8. Most intra-THH cross-links occurred in the least organised domain 5 region at a 3.5-fold higher frequency.
