In 1903 the name trichohyalin was assigned to the granules of the inner root sheath (IRS) of hair follicles discovered by Hans Vörner.[6] In 1986 the name was reassigned to a protein isolated from sheep wool follicles.[7]
Gene location
The human TCHH is located on the long (q) arm of chromosome 1 at region 2 band 1 sub-band 3 (1q21.3), from base pair 152,105,403 to base pair 152,116,368 (map).[8] 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.[9] Gene orthologs were identified in most mammals including mice, chickens, rats, pigs, sheep, horses and other species.[10]
The protein forms frequent links between the heads and tails of the keratin chains and, thus, participates in keratin intermediate filaments (KIF) inter-filamentous cross-linking. It also carries a function of a major reinforcement cross-bridging protein for the cell envelope (CE) barrier structure of the IRS and participates in coordination of CE structure.[11]
Overall, trichohyalin confers mechanical strength to the hair follicle inner root sheath and to other toughened epithelial tissues.[11]
Structure
Trichohyalin belongs to the S100-fused protein family. It is a monomer, containing 1943 amino acids,[14] and has elongated (>200 nm) single-stranded alpha-helical conformation based on its unusually high content of charged residues.[15]
Molecular mass of the human trichohyalin is 253925 Da.[14]
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.[14][15]
Cross-linking by transglutaminase (TGase) enzymes results in the formation of an isopeptide bond between peptide-bound glutamine and lysine residues and provide insolubility and the rigid structure to trichohyalin.[16]
Interactions
TCHH protein is extensively cross-linked to itself in the IRS tissue as well as to keratin intermediate filaments (KIF). All TCHH-keratin links involved only domain 6 or 8 sequences.[11]
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.[11]
^Hamilton EH, Payne RE, O'Keefe EJ (May 1991). "Trichohyalin: presence in the granular layer and stratum corneum of normal human epidermis". The Journal of Investigative Dermatology. 96 (5): 666–72. doi:10.1111/1523-1747.ep12470590. PMID1708794.
^Ü Basmanav FB, Cau L, Tafazzoli A, Méchin MC, Wolf S, Romano MT, Valentin F, Wiegmann H, Huchenq A, Kandil R, Garcia Bartels N, Kilic A, George S, Ralser DJ, Bergner S, Ferguson DJ, Oprisoreanu AM, Wehner M, Thiele H, Altmüller J, Nürnberg P, Swan D, Houniet D, Büchner A, Weibel L, Wagner N, Grimalt R, Bygum A, Serre G, Blume-Peytavi U, Sprecher E, Schoch S, Oji V, Hamm H, Farrant P, Simon M, Betz RC (December 2016). "Mutations in Three Genes Encoding Proteins Involved in Hair Shaft Formation Cause Uncombable Hair Syndrome". American Journal of Human Genetics. 99 (6): 1292–1304. doi:10.1016/j.ajhg.2016.10.004. PMC5142115. PMID27866708.
^Leung MC, Sutton CW, Fenton DA, Tobin DJ (October 2010). "Trichohyalin is a potential major autoantigen in human alopecia areata". Journal of Proteome Research. 9 (10): 5153–63. doi:10.1021/pr100422u. PMID20722389.
Yamamoto S, Hirai K, Hasegawa-Oka Y, Hirai Y (February 2009). "Molecular elements of the regulatory control of keratin filament modulator AHF/trichohyalin in the hair follicle". Experimental Dermatology. 18 (2): 152–9. doi:10.1111/j.1600-0625.2008.00777.x. PMID18643848. S2CID34547087.
Fietz MJ, Rogers GE, Eyre HJ, Baker E, Callen DF, Sutherland GR (November 1992). "Mapping of the trichohyalin gene: co-localization with the profilaggrin, involucrin, and loricrin genes". The Journal of Investigative Dermatology. 99 (5): 542–4. doi:10.1111/1523-1747.ep12667301. PMID1431214.
Leung MC, Sutton CW, Fenton DA, Tobin DJ (October 2010). "Trichohyalin is a potential major autoantigen in human alopecia areata". Journal of Proteome Research. 9 (10): 5153–63. doi:10.1021/pr100422u. PMID20722389.
