Keratinocyte transglutaminase explained

Protein-glutamine gamma-glutamyltransferase K is a transglutaminase enzyme that in humans is encoded by the TGM1 gene.^{[1] [2]}

Function

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.^{[3] [4]} 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.^[5]

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.^[6] 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.

Pathology

A deficiency is associated with ichthyosis lamellaris.^[7] Epidermal transglutaminase is the autoantigen, in humans, of dermatitis herpetiformis.

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. 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.

See also

• Keratinocyte

Further reading

• Phillips MA, Stewart BE, Rice RH . Genomic structure of keratinocyte transglutaminase. Recruitment of new exon for modified function . The Journal of Biological Chemistry . 267 . 4 . 2282–6 . February 1992 . 10.1016/S0021-9258(18)45875-9 . 1346394 . free .
• Kim IG, McBride OW, Wang M, Kim SY, Idler WW, Steinert PM . Structure and organization of the human transglutaminase 1 gene . The Journal of Biological Chemistry . 267 . 11 . 7710–7 . April 1992 . 10.1016/S0021-9258(18)42573-2 . 1348508 . free .
• Polakowska RR, Eickbush T, Falciano V, Razvi F, Goldsmith LA . Organization and evolution of the human epidermal keratinocyte transglutaminase I gene . Proceedings of the National Academy of Sciences of the United States of America . 89 . 10 . 4476–80 . May 1992 . 1350092 . 49105 . 10.1073/pnas.89.10.4476 . 1992PNAS...89.4476P . free .
• Schroeder WT, Thacher SM, Stewart-Galetka S, Annarella M, Chema D, Siciliano MJ, Davies PJ, Tang HY, Sowa BA, Duvic M . 6 . Type I keratinocyte transglutaminase: expression in human skin and psoriasis . The Journal of Investigative Dermatology . 99 . 1 . 27–34 . July 1992 . 1351505 . 10.1111/1523-1747.ep12611394 .
• Yamanishi K, Inazawa J, Liew FM, Nonomura K, Ariyama T, Yasuno H, Abe T, Doi H, Hirano J, Fukushima S . 6 . Structure of the gene for human transglutaminase 1 . The Journal of Biological Chemistry . 267 . 25 . 17858–63 . September 1992 . 10.1016/S0021-9258(19)37122-4 . 1381356 . free .
• Kim HC, Idler WW, Kim IG, Han JH, Chung SI, Steinert PM . 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 . January 1991 . 10.1016/S0021-9258(18)52469-8 . 1670769 . free .
• Yamanishi K, Liew FM, Konishi K, Yasuno H, Doi H, Hirano J, Fukushima S . Molecular cloning of human epidermal transglutaminase cDNA from keratinocytes in culture . Biochemical and Biophysical Research Communications . 175 . 3 . 906–13 . March 1991 . 1673840 . 10.1016/0006-291X(91)91651-R .
• Polakowska R, Herting E, Goldsmith LA . Isolation of cDNA for human epidermal type I transglutaminase . The Journal of Investigative Dermatology . 96 . 2 . 285–8 . February 1991 . 1704039 . 10.1111/1523-1747.ep12464554 .
• Phillips MA, Stewart BE, Qin Q, Chakravarty R, Floyd EE, Jetten AM, Rice RH . Primary structure of keratinocyte transglutaminase . Proceedings of the National Academy of Sciences of the United States of America . 87 . 23 . 9333–7 . December 1990 . 1979171 . 55159 . 10.1073/pnas.87.23.9333 . 1990PNAS...87.9333P . free .
• Candi E, Melino G, Mei G, Tarcsa E, Chung SI, Marekov LN, Steinert PM . Biochemical, structural, and transglutaminase substrate properties of human loricrin, the major epidermal cornified cell envelope protein . The Journal of Biological Chemistry . 270 . 44 . 26382–90 . November 1995 . 7592852 . 10.1074/jbc.270.44.26382 . free .
• Mariniello L, Esposito C, Di Pierro P, Cozzolino A, Pucci P, Porta R . 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 . July 1993 . 7688299 . 10.1111/j.1432-1033.1993.tb18011.x . free .
• Russell LJ, DiGiovanna JJ, Rogers GR, Steinert PM, Hashem N, Compton JG, Bale SJ . Mutations in the gene for transglutaminase 1 in autosomal recessive lamellar ichthyosis . Nature Genetics . 9 . 3 . 279–83 . March 1995 . 7773290 . 10.1038/ng0395-279 . 27032821 .
• Huber M, Rettler I, Bernasconi K, Frenk E, Lavrijsen SP, Ponec M, Bon A, Lautenschlager S, Schorderet DF, Hohl D . 6 . Mutations of keratinocyte transglutaminase in lamellar ichthyosis . Science . 267 . 5197 . 525–8 . January 1995 . 7824952 . 10.1126/science.7824952 . 1995Sci...267..525H . 43324754 .
• Amendola A, Lombardi G, Oliverio S, Colizzi V, Piacentini M . 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 . February 1994 . 7906657 . 10.1016/0014-5793(94)80427-3 . 39872629 . free .
• Kim SY, Kim IG, Chung SI, Steinert PM . 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 . November 1994 . 10.1016/S0021-9258(18)46883-4 . 7961731 . free .
• Steinert PM, Kim SY, Chung SI, Marekov LN . The transglutaminase 1 enzyme is variably acylated by myristate and palmitate during differentiation in epidermal keratinocytes . The Journal of Biological Chemistry . 271 . 42 . 26242–50 . October 1996 . 8824274 . 10.1074/jbc.271.39.24105 . free .
• Laiho E, Ignatius J, Mikkola H, Yee VC, Teller DC, Niemi KM, Saarialho-Kere U, Kere J, Palotie A . 6 . Transglutaminase 1 mutations in autosomal recessive congenital ichthyosis: private and recurrent mutations in an isolated population . American Journal of Human Genetics . 61 . 3 . 529–38 . September 1997 . 9326318 . 1715945 . 10.1086/515498 .
• Tarcsa E, Marekov LN, Andreoli J, Idler WW, Candi E, Chung SI, Steinert PM . The fate of trichohyalin. Sequential post-translational modifications by peptidyl-arginine deiminase and transglutaminases . The Journal of Biological Chemistry . 272 . 44 . 27893–901 . October 1997 . 9346937 . 10.1074/jbc.272.44.27893 . free .
• Petit E, Huber M, Rochat A, Bodemer C, Teillac-Hamel D, Müh JP, Revuz J, Barrandon Y, Lathrop M, de Prost Y, Hohl D, Hovnanian A . 6 . 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 . 1998 . 9359043 . 10.1159/000484767 .
• Iwasaki W, Nagata K, Hatanaka H, Inui T, Kimura T, Muramatsu T, Yoshida K, Tasumi M, Inagaki F . 6 . Solution structure of midkine, a new heparin-binding growth factor . The EMBO Journal . 16 . 23 . 6936–46 . December 1997 . 9384573 . 1170297 . 10.1093/emboj/16.23.6936 .

Notes and References

1. Grenard P, Bates MK, Aeschlimann D . Evolution of transglutaminase genes: identification of a transglutaminase gene cluster on human chromosome 15q15. Structure of the gene encoding transglutaminase X and a novel gene family member, transglutaminase Z . The Journal of Biological Chemistry . 276 . 35 . 33066–78 . August 2001 . 11390390 . 10.1074/jbc.M102553200 . free .
2. Web site: Entrez Gene: TGM1 transglutaminase 1 (K polypeptide epidermal type I, protein-glutamine-gamma-glutamyltransferase) .
3. Eckert RL, Sturniolo MT, Broome AM, Ruse M, Rorke EA . Transglutaminase function in epidermis . The Journal of Investigative Dermatology . 124 . 3 . 481–92 . March 2005 . 15737187 . 10.1111/j.0022-202X.2005.23627.x . free .
4. Huber M, Rettler I, Bernasconi K, Frenk E, Lavrijsen SP, Ponec M, Bon A, Lautenschlager S, Schorderet DF, Hohl D . 6 . Mutations of keratinocyte transglutaminase in lamellar ichthyosis . Science . 267 . 5197 . 525–8 . January 1995 . 7824952 . 10.1126/science.7824952 . 1995Sci...267..525H . 43324754 .
5. Eckert RL, Sturniolo MT, Broome AM, Ruse M, Rorke EA . Transglutaminase function in epidermis . The Journal of Investigative Dermatology . 124 . 3 . 481–92 . March 2005 . 15737187 . 10.1111/j.0022-202X.2005.23627.x . free .
6. Kim SY, Jeitner TM, Steinert PM . Transglutaminases in disease . Neurochemistry International . 40 . 1 . 85–103 . January 2002 . 11738475 . 10.1016/s0197-0186(01)00064-x . 23418803 .
7. Hennies HC, Küster W, Wiebe V, Krebsová A, Reis A . Genotype/phenotype correlation in autosomal recessive lamellar ichthyosis . American Journal of Human Genetics . 62 . 5 . 1052–61 . May 1998 . 9545389 . 1377076 . 10.1086/301818 .