Keratinocyte transglutaminase enzymes serve to specifically catalyze the development of the cornified cell envelope, a defining characteristic of epidermal keratinocytes that have undergone the termination of differentiation.[7][8] The specific cross linkages formed by keratinocyte transglutaminase are between n^ε-(γ-glutamyl)lysine residues which develop into isopeptide protein-protein linkages that adds to the stabilization of the cornified cell envelope.[9]
In terminally differentiated stratified squamous epithelia, the cornified cell envelope protein linkages allow for a structurally fortified, yet flexible (15 nm thick) layer to the place of the cell membrane, acting as a highly insoluble barrier.[10] The expression of the enzyme is most highly exhibited along the biological membrane of these fully formed epithelial cells, preventing the cell from undergoing chemical and or physical damages. A lesser amount of enzymatic activity, of the TGK genes (5-10%), lies within the cytoplasmic fraction of such cells, allowing for finalization of the cross-linkaging necessary for the full functionality of the cornified cell envelope.
A study on the mutation of Keratinocyte transglutaminase (TGK) came to conclude that those affected with ichthyosis lamellaris, present a substantial deficit in keratinocyte transglutaminase activity.[8]It was concluded that those afflicted, display a decrease in activity of the enzyme, as a result of a lessened amount of transcription of the human TGK gene. This lack of protein stems from a common mutation of the TGK gene, which exists in two possible variants, found at the TGM1 locus on the 14q11 chromosome, as exhibited amongst all the subjects of the study. Such mutations were of the compound heterozygous or homozygous variety, which leads to the expression of lamellar ichthyosis as a result of abnormal cross-linkaging of the cornified cell envelope.
^Eckert RL, Sturniolo MT, Broome AM, Ruse M, Rorke EA (March 2005). "Transglutaminase function in epidermis". The Journal of Investigative Dermatology. 124 (3): 481–92. doi:10.1111/j.0022-202X.2005.23627.x. PMID15737187.
^ abHuber M, Rettler I, Bernasconi K, Frenk E, Lavrijsen SP, Ponec M, et al. (January 1995). "Mutations of keratinocyte transglutaminase in lamellar ichthyosis". Science. 267 (5197): 525–8. Bibcode:1995Sci...267..525H. doi:10.1126/science.7824952. PMID7824952.
^Eckert RL, Sturniolo MT, Broome AM, Ruse M, Rorke EA (March 2005). "Transglutaminase function in epidermis". The Journal of Investigative Dermatology. 124 (3): 481–92. doi:10.1111/j.0022-202X.2005.23627.x. PMID15737187.
Phillips MA, Stewart BE, Rice RH (February 1992). "Genomic structure of keratinocyte transglutaminase. Recruitment of new exon for modified function". The Journal of Biological Chemistry. 267 (4): 2282–6. PMID1346394.
Kim IG, McBride OW, Wang M, Kim SY, Idler WW, Steinert PM (April 1992). "Structure and organization of the human transglutaminase 1 gene". The Journal of Biological Chemistry. 267 (11): 7710–7. PMID1348508.
Yamanishi K, Inazawa J, Liew FM, Nonomura K, Ariyama T, Yasuno H, et al. (September 1992). "Structure of the gene for human transglutaminase 1". The Journal of Biological Chemistry. 267 (25): 17858–63. PMID1381356.
Kim HC, Idler WW, Kim IG, Han JH, Chung SI, Steinert PM (January 1991). "The complete amino acid sequence of the human transglutaminase K enzyme deduced from the nucleic acid sequences of cDNA clones". The Journal of Biological Chemistry. 266 (1): 536–9. PMID1670769.
Yamanishi K, Liew FM, Konishi K, Yasuno H, Doi H, Hirano J, Fukushima S (March 1991). "Molecular cloning of human epidermal transglutaminase cDNA from keratinocytes in culture". Biochemical and Biophysical Research Communications. 175 (3): 906–13. doi:10.1016/0006-291X(91)91651-R. PMID1673840.
Mariniello L, Esposito C, Di Pierro P, Cozzolino A, Pucci P, Porta R (July 1993). "Human-immunodeficiency-virus transmembrane glycoprotein gp41 is an amino acceptor and donor substrate for transglutaminase in vitro". European Journal of Biochemistry. 215 (1): 99–104. doi:10.1111/j.1432-1033.1993.tb18011.x. PMID7688299.
Russell LJ, DiGiovanna JJ, Rogers GR, Steinert PM, Hashem N, Compton JG, Bale SJ (March 1995). "Mutations in the gene for transglutaminase 1 in autosomal recessive lamellar ichthyosis". Nature Genetics. 9 (3): 279–83. doi:10.1038/ng0395-279. PMID7773290.
Huber M, Rettler I, Bernasconi K, Frenk E, Lavrijsen SP, Ponec M, et al. (January 1995). "Mutations of keratinocyte transglutaminase in lamellar ichthyosis". Science. 267 (5197): 525–8. Bibcode:1995Sci...267..525H. doi:10.1126/science.7824952. PMID7824952.
Amendola A, Lombardi G, Oliverio S, Colizzi V, Piacentini M (February 1994). "HIV-1 gp120-dependent induction of apoptosis in antigen-specific human T cell clones is characterized by 'tissue' transglutaminase expression and prevented by cyclosporin A". FEBS Letters. 339 (3): 258–64. doi:10.1016/0014-5793(94)80427-3. PMID7906657.
Kim SY, Kim IG, Chung SI, Steinert PM (November 1994). "The structure of the transglutaminase 1 enzyme. Deletion cloning reveals domains that regulate its specific activity and substrate specificity". The Journal of Biological Chemistry. 269 (45): 27979–86. PMID7961731.
Petit E, Huber M, Rochat A, Bodemer C, Teillac-Hamel D, Müh JP, et al. (1998). "Three novel point mutations in the keratinocyte transglutaminase (TGK) gene in lamellar ichthyosis: significance for mutant transcript level, TGK immunodetection and activity". European Journal of Human Genetics. 5 (4): 218–28. doi:10.1159/000484767. PMID9359043.