The cross-links help provide strength and structure to the cells skin and hair cells. Chromosomal location of Transglutaminase 3 is located on chromosome 20.An experiment was done where Transglutaminase 3 reduced in esophageal cancer. They used western blot analysis and polymerase chain reaction. With the 58 pairs of tissues that were sampled, it was confirmed that Transglutaminase 3 is closely related to growth proliferation and migration. However, the over-expression of this gene induces cell proliferation, migration, and invasion, and promotes programmed cell death. This came to show that Transglutaminse 3 will be a candidate growth and could function as a helpful biomarker and a therapeutic target to esophageal cancer treatment. Uncombable Hair Syndrome 3
Uncombable Hair Syndrome 3 is caused by a defect in the PADI3 gene (peptidylarginine-deiminase 3) and is located on chromosome 1. This defect apparently is the most common cause of UHS. The PADI3 gene provides instructions for creating an enzyme called peptidylargine deiminase 3. PADI3 is found within the skins extreme external surface, inside cells called karinocytes. The protein also contributes to hair follicles that are specialized structures within the skin where development happens. In these hair follicles, the PADI3 gene adjusts proteins that are giving structure to the hair strand. The PADI3 gene also involves a process called deimination. This process modifies the proteins intuitive with other proteins.An experiment was performed in where the PADI3 is found in central centrifugal cicatricial alopecia which is mostly found in African women that suggests an autosomal dominant trait to occur.
Trichohyalin (TCHH) is a structural protein responsible for the proper cylindrical fiber topology of the hair shaft. TCHH binds other TCHH and keratin-intermediate filaments creating the proper cross-links and cylindrical shape of the hair shaft. PADI3 and TGM3 are two enzymes responsible for post-translational modification of TCHH important for cross-linking of TCHH within the hair. In Uncombable Hair Syndrome mutations in TCHH, PADI3, or TGM3 result in improper cross-linking and the resulting irregular shape of the hair shaft.The particular defect in TCHH as a structural component of hair may be a defect of deimination. Deimination converts the amino acid arginine to the amino acid citrulline. This conversion is done by calcium-dependent enzymes known as peptidylarginine deiminases (PADs). PADI3 is a member of this enzyme class. One study reported PAD involvement in skin and skin-related diseases, particularly at the hair follicle. Alterations to PAD activity resulted in the development of Uncombable Hair Syndrome. Another study examined the transglutaminase (TG) family of enzymes and their involvement in UHS. This family of enzymes includes TGM3, which is expressed in epidermal cells. Mutations in TGM3 may therefore reduce or alter the intermolecular cross-linking important for hair shaft formation, leading to Uncombable Hair Syndrome.Another molecular mechanism of UHS was proposed by Ralph Trueb in 2003. He suggested that premature keratinization of the inner hair root forms a rigid sheath that alters the shape of a hair strand as it grows out of the root.