Disease relevance of TGM5

• To explore the expression and gain more information on the function of transglutaminase 5 enzyme in normal and defective human epidermis, we generated a rat antihuman transglutaminase 5 antiserum elicited against a purified active recombinant protein expressed in the baculovirus system [1].
• We observed that transglutaminase 5 contributes, as a secondary effect, to the hyperkeratotic phenotype in ichthyosis (both vulgaris and lamellar) and in psoriasis [1].
• In Darier's disease, transglutaminase 5 expression, as well as transglutaminase 3, is completely missregulated, being overexpressed or totally absent in different areas of the same lesion [1].
• Morphometric analysis demonstrated a significant reduction in both intramyelinic and interstitial edema in the white matter of the spinal cord (SC) of totally gastrectomized (TGX) rats after treatment [2].
• The totally gastrectomized (TGX) rat is a new experimental model for studying the pathogenesis of cobalamin (Cbl)-deficient myelopathy, i.e., subacute combined degeneration, total gastrectomy (TG) serving as a surgical paradigm of human pernicious anemia [3].

High impact information on TGM5

• Other families with more-widespread peeling skin phenotypes lacked TGM5 mutations [4].
• A homozygous missense mutation in TGM5 abolishes epidermal transglutaminase 5 activity and causes acral peeling skin syndrome [4].
• Three-dimensional modeling of TG5 showed that G113C lies close to the catalytic domain, and, furthermore, that this glycine residue is conserved in all known transglutaminases, which is consistent with pathogenicity [4].
• We isolated and characterized the gene encoding human transglutaminase (TG)(X) (TGM5) and mapped it to the 15q15.2 region of chromosome 15 by fluorescence in situ hybridization [5].
• Kinetic and in vitro cross-linking experiments indicate that full-length TGase 5 is very efficient in using specific epidermal substrates (loricrin, involucrin, and SPR3) [6].

Biological context of TGM5

• Overexpressed transglutaminase 5 triggers cell death [7].
• In addition to the previously described isoforms, full-length TGase 5 and Delta3 (deletion of exon 3), we identified two new splicing variants, Delta11 and Delta3Delta11 (deletion of exons 11 or 3, 11) [6].

Anatomical context of TGM5

• TGX expression increased severalfold when keratinocyte cultures were induced to differentiate by suspension or growth to postconfluency, suggesting that TGX contributes to the formation of the cornified envelope [8].
• Transglutaminase 5 expression in human hair follicle [9].
• Moreover, in situ measurement of TGase activity shows that endogenous TGase 5 is active upon treatment with phorbol acetate, and the enzyme co-localises with vimentin intermediate filaments [10].
• In both TGX-rats and in rats chronically fed a Cbl-deficient diet the pyramidal tract and the optic nerve were completely spared [11].

Associations of TGM5 with chemical compounds

• Chronic peroral administration of the antibiotic lincomycin to TGX rats in an attempt to suppress the enteric flora markedly decreased serum MMA levels [3].
• The concentrations of MMA, MCA, and cystathionine were increased in kidney, liver, and spinal cord (SC) of TGX rats at 10 months [3].

Co-localisations of TGM5

• Indeed, TGase 5 co-localize with vimentin and it is able to cross-link vimentin in vitro [6].

Other interactions of TGM5

• A full-length cDNA for the novel transglutaminase (TGX) was obtained by anchored PCR [8].

Analytical, diagnostic and therapeutic context of TGM5

• By use of Western blotting and immunofluorescence methods, the immunospecificity of the antibodies for transglutaminase 5 was tested; no crossreactivity with other transglutaminases (types 1, 2, and 3) was observed, thus allowing histochemistry studies [1].

References