TGM1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2XZZ
Identifiers
Aliases	TGM1, ARCI1, ICR2, KTG, LI, LI1, TGASE, TGK, transglutaminase 1
External IDs	OMIM: 190195 MGI: 98730 HomoloGene: 306 GeneCards: TGM1
Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q12 Start 24,249,114 bp[1] End 24,264,432 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14|14 C3 Start 55,937,466 bp[2] End 55,951,383 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of abdomen vagina thymus minor salivary gland tibial nerve upper lobe of left lung uterine tube right uterine tube sural nerve left uterine tube Top expressed in esophagus lip yolk sac proximal tubule skin of abdomen skin of back epidermis iris belly cord hair follicle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity acyltransferase activity protein binding metal ion binding protein-glutamine gamma-glutamyltransferase activity Cellular component intrinsic component of membrane extracellular exosome membrane cornified envelope cytosol plasma membrane Biological process cell envelope organization keratinization positive regulation of keratinocyte proliferation positive regulation of cell cycle keratinocyte differentiation cornification peptide cross-linking Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7051 21816 Ensembl ENSG00000092295 ENSG00000285348 ENSMUSG00000022218 UniProt P22735 Q9JLF6 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 Mb Chr 14: 55.94 – 55.95 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

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.^[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

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.