Keratinocyte transglutaminase

TGM1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTGM1, ARCI1, ICR2, KTG, LI, LI1, TGASE, TGK, transglutaminase 1
External IDsOMIM: 190195; MGI: 98730; HomoloGene: 306; GeneCards: TGM1; OMA:TGM1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000359

NM_001161714
NM_001161715
NM_019984

RefSeq (protein)

NP_000350

NP_001155186
NP_001155187
NP_064368

Location (UCSC)Chr 14: 24.25 – 24.26 MbChr 14: 55.94 – 55.95 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Protein-glutamine gamma-glutamyltransferase K is a transglutaminase enzyme that in humans is encoded by the TGM1 gene.[5][6]

Function

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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.

Pathology

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A deficiency is associated with ichthyosis lamellaris.[11] 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.[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.

See also

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References

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  1. ^ a b c ENSG00000285348 GRCh38: Ensembl release 89: ENSG00000092295, ENSG00000285348Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022218Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Grenard P, Bates MK, Aeschlimann D (August 2001). "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. doi:10.1074/jbc.M102553200. PMID 11390390.
  6. ^ "Entrez Gene: TGM1 transglutaminase 1 (K polypeptide epidermal type I, protein-glutamine-gamma-glutamyltransferase)".
  7. ^ 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. PMID 15737187.
  8. ^ a b 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. PMID 7824952. S2CID 43324754.
  9. ^ 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. PMID 15737187.
  10. ^ Kim SY, Jeitner TM, Steinert PM (January 2002). "Transglutaminases in disease". Neurochemistry International. 40 (1): 85–103. doi:10.1016/s0197-0186(01)00064-x. PMID 11738475. S2CID 23418803.
  11. ^ Hennies HC, Küster W, Wiebe V, Krebsová A, Reis A (May 1998). "Genotype/phenotype correlation in autosomal recessive lamellar ichthyosis". American Journal of Human Genetics. 62 (5): 1052–61. doi:10.1086/301818. PMC 1377076. PMID 9545389.

Further reading

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