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Literature summary for 2.3.2.13 extracted from
- Transglutaminase diseases from biochemistry to the bedside (2019), FASEB J., 33, 3-12 .
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | for analysis of the effect of TG2 deficiency, two independent groups of TG2 knockout mouse models are generated, one a global TG2 knockout fromconception and the other offering the versatility of the Cre/loxP site-specific recombination system to generate, in a temporally specific manner, global knockouts or tissue-specific knockouts | Mus musculus |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| cystamine | - |
Homo sapiens |  |
| cystamine | - |
Mus musculus | |
| Monodansylcadaverine | - |
Homo sapiens | |
| Monodansylcadaverine | - |
Mus musculus | |
| additional information | poor inhibition by ZED1227, an irreversible peptidomimetic TG2-selective inhibitor; poor inhibition by ZED1227, an irreversible peptidomimetic TG2-selective inhibitor; poor inhibition by ZED1227, an irreversible peptidomimetic TG2-selective inhibitor | Homo sapiens | |
| ZED1227 | an irreversible peptidomimetic TG2-selective inhibitor | Homo sapiens | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytoplasm | - |
Homo sapiens | 5737 | - |
| extracellular | extracellular matrix | Homo sapiens | - |
- |
| extracellular | extracellular matrix | Mus musculus | - |
- |
| intracellular | intracellular TG1 activity is unlikely to contribute extracellularly to extracellular matrix crosslinking | Homo sapiens | 5622 | - |
| membrane | - |
Homo sapiens | 16020 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| protein glutamine + alkylamine | Homo sapiens | - |
protein N5-alkylglutamine + NH3 | - |
? | |
| protein glutamine + alkylamine | Mus musculus | - |
protein N5-alkylglutamine + NH3 | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | O43548 | - |
- |
| Homo sapiens | O95932 | - |
- |
| Homo sapiens | P16452 | - |
- |
| Homo sapiens | P21980 | - |
- |
| Homo sapiens | P22735 | - |
- |
| Homo sapiens | P49221 | - |
- |
| Homo sapiens | Q08188 | - |
- |
| Homo sapiens | Q96PF1 | - |
- |
| Mus musculus | P21981 | - |
- |
| Mus musculus | Q9JLF6 | - |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| corneocyte | - |
Homo sapiens | - |
| epidermis | - |
Mus musculus | - |
| epidermis | - |
Homo sapiens | - |
| erythrocyte | - |
Homo sapiens | - |
| erythrocyte | - |
Mus musculus | - |
| hair | follicle and cortex and cuticle of the hair shaft | Homo sapiens | - |
| hair follicle | - |
Homo sapiens | - |
| intestine | - |
Mus musculus | - |
| intestine | TG2 is not normally active in the lamina propria, but inflammatory signals have been implicated in its activation. Avirulent-reovirus in the presence of dietary gluten activates villous TG2 | Homo sapiens | - |
| keratinocyte | - |
Homo sapiens | - |
| kidney | - |
Mus musculus | - |
| kidney | TG1 and TG2 are the most abundantly expressed TGs in normal kidney | Homo sapiens | - |
| additional information | TG3 is expressed in the cytoplasm of late-differentiating keratinocytes and corneocytes and in the cortex and cuticle of the hair shaft and hair follicles | Homo sapiens | - |
| prostate gland | TG4 expression is restricted to the prostate gland | Homo sapiens | - |
| renal tubule epithelium | - |
Homo sapiens | - |
| skin | - |
Mus musculus | - |
| skin | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | protein 4.2 has ATPase activity. Noncatalytic structural role of protein 4.2 | Homo sapiens | ? | - |
- |
|
| protein glutamine + alkylamine | - |
Homo sapiens | protein N5-alkylglutamine + NH3 | - |
? | |
| protein glutamine + alkylamine | - |
Mus musculus | protein N5-alkylglutamine + NH3 | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| EPB42 | - |
Homo sapiens |
| protein 4.2 | - |
Homo sapiens |
| TG1 | - |
Mus musculus |
| TG1 | - |
Homo sapiens |
| TG2 | - |
Homo sapiens |
| TG2 | - |
Mus musculus |
| TG3 | - |
Homo sapiens |
| TG4 | - |
Homo sapiens |
| TG5 | - |
Homo sapiens |
| TG6 | - |
Homo sapiens |
| TG7 | - |
Homo sapiens |
| TGM1 | - |
Mus musculus |
| TGM1 | - |
Homo sapiens |
| TGM2 | - |
Homo sapiens |
| TGM2 | - |
Mus musculus |
| TGM3 | - |
Homo sapiens |
| TGM4 | - |
Homo sapiens |
| TGM5 | - |
Homo sapiens |
| TGM6 | - |
Homo sapiens |
| TGM7 | - |
Homo sapiens |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | double-TG1/TG2 knockout mice show epidermal features similar to TG1 knockout mice. Double-FXIII-A/TG2 knockout mice exhibit only a transient delay in bone mineral density and growth relative to wild-type mice | Mus musculus |
| malfunction | effective inhibition of renal interstitial fibrosis by TG inhibitors but only partial reduction of fibrosis in TG2 knockout mice | Mus musculus |
| malfunction | loss of TG1 and TG5 cross linking leads to defects in epidermal cornification in lamellar ichthyosis and acral peeling skin syndrome, respectively. Homozygous missense mutations in the gene encoding TG5 are found to correlate with acral peeling skin syndrome, which is characterized by continual shedding of the outer epidermis of the dorsa of the hands and feet from birth and throughout life | Homo sapiens |
| malfunction | loss of TG1 and TG5 cross linking leads to defects in epidermal cornification in lamellar ichthyosis and acral peeling skin syndrome, respectively. Lamellar ichthyosis is apparent at birth, with newborns encased in a shiny, waxy layer of skin (collodion babies) that sheds to reveal scaling and shedding of the outer epidermis and a severely compromised skin barrier. It is an autosomal-recessive disease, with mutations in the gene encoding TG1 accounting for about 90% of cases. Lamellar ichthyosis is an orphan disease. TG1 and TG2 are the most abundantly expressed TGs in normal kidney, and renal disease progression correlates with increases in activity of intracellular TG1 in renal tubular epithelium and of TG2 in the extracellular matrix | Homo sapiens |
| malfunction | loss of TG3 crosslinking in hair-cuticle formation leads to uncombable hair syndrome. A homozygous nonsense mutation of TG3 correlates with uncombable hair syndrome and the absence of TG3-mediated crosslinks between trichohyalin and keratin intermediate filaments | Homo sapiens |
| malfunction | loss of TG6 crosslinking leads to spinocerebellar ataxia-35 | Homo sapiens |
| malfunction | loss of the structural erythrocyte membrane protein, protein 4.2, leads to hereditary spherocytosis type 5 associated with abnormally shaped, osmotically fragile erythrocytes | Homo sapiens |
| malfunction | TG1 and TG2 are the most abundantly expressed TGs in normal kidney, and renal disease progression correlates with increases in activity of intracellular TG1 in renal tubular epithelium and of TG2 in the extracellular matrix. Yet no diseases have been correlated with TG2 deficiency. TG2 deletion does not improve motor, cognitive, molecular, histologic, or lifespan phenotypes and is thus not an important factor in Huntington's disease pathology | Homo sapiens |
| malfunction | TG1 knockout mice show defective epidermal maturation late in embryonic development, resulting in a drastic increase in skin permeability, but unlike human patients, TG1 knockout mice die from dehydration within a few hours of birth. Double-TG1/TG2 knockout mice show epidermal features similar to TG1 knockout mice | Mus musculus |
| metabolism | in general, TG-catalyzed crosslinking is the primary mechanism by which TGs promote disease progression | Homo sapiens |
| physiological function | essential role for membrane-bound TG1 in cornified envelope assembly | Mus musculus |
| physiological function | in humans, 9 members of the transglutaminase (TG) family have been identified, of which eight (factor XIII (FXIII) A and TG1-TG7) catalyze posttranslational protein-modifying reactions, and one (protein 4.2) does not. The TG enzymatic activities considered for human disease include deamidation of glutamine (Gln) residues, amine incorporation into Gln residues, and protein crosslinking. Essential role for membrane-bound TG1 in cornified envelope assembly. TG1 may contribute to intracellular crosslinking processes. Intracellular TG1 activity is unlikely to contribute extracellularly to extracellular matrix crosslinking | Homo sapiens |
| physiological function | in humans, 9 members of the transglutaminase (TG) family have been identified, of which eight (factor XIII (FXIII) A and TG1-TG7) catalyze posttranslational protein-modifying reactions, and one (protein 4.2) does not. The TG enzymatic activities considered for human disease include deamidation of glutamine (Gln) residues, amine incorporation into Gln residues, and protein crosslinking. TG3 is an autoantigen, causing autoantibody production, in dermatitis herpetiformis | Homo sapiens |
| physiological function | in humans, 9 members of the transglutaminase (TG) family have been identified, of which eight (factor XIII (FXIII) A and TG1-TG7) catalyze posttranslational protein-modifying reactions, and one (protein 4.2) does not. The TG enzymatic activities considered for human disease include deamidation of glutamine (Gln) residues, amine incorporation into Gln residues, and protein crosslinking. TG4 is an autoantigen, causing autoantibody production, in autoimmume polyglandular syndrome type 1. Role of TG4 in cancer | Homo sapiens |
| physiological function | in humans, 9 members of the transglutaminase (TG) family have been identified, of which eight (factor XIII (FXIII) A and TG1-TG7) catalyze posttranslational protein-modifying reactions, and one (protein 4.2) does not. The TG enzymatic activities considered for human disease include deamidation of glutamine (Gln) residues, amine incorporation into Gln residues, and protein crosslinking. TG5 is not an autoantigen and does not cause autoantibody production. Role for the cytoplasmic TG5 in epidermal cornification | Homo sapiens |
| physiological function | in humans, 9 members of the transglutaminase (TG) family have been identified, of which eight (factor XIII (FXIII) A and TG1-TG7) catalyze posttranslational protein-modifying reactions, and one (protein 4.2) does not. The TG enzymatic activities considered for human disease include deamidation of glutamine (Gln) residues, amine incorporation into Gln residues, and protein crosslinking. TG6 is an autoantigen, causing autoantibody production, in gluten axonal neuropathy and gluten ataxia | Homo sapiens |
| physiological function | in humans, 9 members of the transglutaminase (TG) family have been identified, of which eight (factor XIII (FXIII) A and TG1-TG7) catalyze posttranslational protein-modifying reactions, and one (protein 4.2) does not. The TG enzymatic activities considered for human disease include deamidation of glutamine (Gln) residues, amine incorporation into Gln residues, and protein crosslinking. TG7 is not an autoantigen and does not cause autoantibody production | Homo sapiens |
| physiological function | in humans, 9 members of the transglutaminase (TG) family have been identified, of which eight (factor XIII (FXIII) A and TG1-TG7) catalyze posttranslational protein-modifying reactions, and one (protein 4.2) does not. The TG enzymatic activities considered for human disease include deamidation of glutamine (Gln) residues, amine incorporation into Gln residues, and protein crosslinking. The enzymatic activity of TG2 is involved in the exacerbation of celiac disease. TG2 has been identified as the principal autoantigen recognized by disease-specific autoantibodies in the serum of patientswith active celiac disease. And TGS is involved in at least one case of hemoglobinopathy, characterized by shortened erythrocyte lifespan. TG2-mediated formation of crosslinked supramolecular membrane proteins and the resultant stiffening of the erythrocyte membrane by these polymers contribute to the extra-rapid clearing of erythrocytes from the circulation and hence, the shortened lifespan of Hb-Koeln erythrocytes, from 120 to 31 days. TG2 might contribute to neurologic diseases by affecting transcription, cellular differentiation, or cell migration and adhesion. TG2 is implicated in Huntington's disease pathogenesis. TG2 is implicated in extracellular collagen crosslinking. TG2 has been reported to enhance cancer cellmotility through induction of epithelial-to-mesenchymal transition, and TG2 enzymatic activity has been reported to be required for the development and survival of cancer stem cells. TG2 is an autoantigen, causing autoantibody production, in celiac disease | Homo sapiens |
| physiological function | in humans, 9 members of the transglutaminase (TG) family have been identified, of which eight (factor XIII (FXIII) A and TG1-TG7) catalyze posttranslational protein-modifying reactions, and one (protein 4.2) does not. The TG enzymatic activities considered for human disease include deamidation of glutamine (Gln) residues, amine incorporation into Gln residues, and protein crosslinking. The noncatalytic structural role of protein 4.2 is clearly important for erythrocyte membrane integrity | Homo sapiens |
| physiological function | TG2 is involved in extracellular collagen crosslinking | Mus musculus |
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