Tissue transglutaminase
Encyclopedia
Tissue transglutaminase (abbreviated as TG2 or tTG) is an enzyme
of the transglutaminase
family. Like other transglutaminases, it crosslinks protein
s between an ε-amino group of a lysine residue and a γ-carboxamide group of glutamine
residue, creating an inter- or intramolecular bond that is highly resistant to proteolysis
(protein degradation). It is particularly notable for being the autoantigen
in coeliac disease
, but is also known to play a role in apoptosis
, cellular differentiation
, and matrix
stabilisation.
as a cofactor for transamidation activity. Transcription is increased by retinoic acid
. Among its many supposed functions, it appears to play a role in wound healing
, apoptosis
, and extracellular matrix
development
TG2 also has GTPase
activity: In the presence of GTP, it suggested to function as a G protein participating in signaling processes. Besides its transglutaminase activity, TG2 is proposed to also act as kinase, and protein disulfide isomerase, and deamidase. This latter activity is important in the deamidation of gliadin peptides, thus playing important role in the pathology of coeliac disease
.
. Anti-transglutaminase antibodies
(ATA) result in a form of gluten sensitivity
in which a cellular response to Triticeae glutens
that are crosslinked to tTG are able to stimulate transglutaminase specific B-cell responses that eventually result in the production of ATA IgA and IgG.
Recent studies suggest that tTG plays a role in inflammation
, degenerative diseases, and tumor biology.
for anti-tTG antibodies
has superseded older serological tests (anti-endomysium, anti-gliadin, and anti-reticulin) and has a strong sensitivity (99%) and specificity (>90%) for identifying coeliac disease. Modern anti-tTG assays rely on a human recombinant protein as an antigen
in certain tumors.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
of the transglutaminase
Transglutaminase
Transglutaminases are a family of enzymes that catalyze the formation of a covalent bond between a free amine group and the gamma-carboxamid group of protein- or peptide-bound glutamine. Bonds formed by transglutaminase exhibit high resistance to proteolytic degradation.Transglutaminases were...
family. Like other transglutaminases, it crosslinks protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s between an ε-amino group of a lysine residue and a γ-carboxamide group of glutamine
Glutamine
Glutamine is one of the 20 amino acids encoded by the standard genetic code. It is not recognized as an essential amino acid but may become conditionally essential in certain situations, including intensive athletic training or certain gastrointestinal disorders...
residue, creating an inter- or intramolecular bond that is highly resistant to proteolysis
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
(protein degradation). It is particularly notable for being the autoantigen
Autoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...
in coeliac disease
Coeliac disease
Coeliac disease , is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward...
, but is also known to play a role in apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
, cellular differentiation
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
, and matrix
Extracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
stabilisation.
Physiology
tTG is expressed ubiquitously. It requires calciumCalcium in biology
Calcium plays a pivotal role in the physiology and biochemistry of organisms and the cell. It plays an important role in signal transduction pathways, where it acts as a second messenger, in neurotransmitter release from neurons, contraction of all muscle cell types, and fertilization...
as a cofactor for transamidation activity. Transcription is increased by retinoic acid
Retinoic acid
Retinoic acid is a metabolite of vitamin A that mediates the functions of vitamin A required for growth and development. Retinoic acid is required in chordate animals which includes all higher animals from fishes to humans...
. Among its many supposed functions, it appears to play a role in wound healing
Wound healing
Wound healing, or cicatrisation, is an intricate process in which the skin repairs itself after injury. In normal skin, the epidermis and dermis exists in a steady-state equilibrium, forming a protective barrier against the external environment...
, apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
, and extracellular matrix
Extracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
development
TG2 also has GTPase
GTPase
GTPases are a large family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate . The GTP binding and hydrolysis takes place in the highly conserved G domain common to all GTPases.-Functions:...
activity: In the presence of GTP, it suggested to function as a G protein participating in signaling processes. Besides its transglutaminase activity, TG2 is proposed to also act as kinase, and protein disulfide isomerase, and deamidase. This latter activity is important in the deamidation of gliadin peptides, thus playing important role in the pathology of coeliac disease
Coeliac disease
Coeliac disease , is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward...
.
Role in disease
Tissue transglutaminase is best known for its link with coeliac diseaseCoeliac disease
Coeliac disease , is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward...
. Anti-transglutaminase antibodies
Anti-transglutaminase antibodies
Anti-transglutaminase antibodies are autoantibodies against the transglutaminase protein. Antibodies serve an important role in the immune system by detecting cells and substances that the rest of the immune system then eliminates. These cells and substance can be foreign and also can be producd...
(ATA) result in a form of gluten sensitivity
Gluten sensitivity
Gluten sensitivity belongs to a spectrum of disorders in which gluten has an adverse effect on the body. It can be defined as a non-allergic and non-autoimmune condition in which the consumption of gluten can lead to symptoms similar to those observed in coeliac disease or wheat allergy .Gluten...
in which a cellular response to Triticeae glutens
Triticeae glutens
Triticeae glutens are seed storage proteins found in mature seeds of grass tribe Triticeae. Seed glutens of non-Triticeae plants have varieties of similar properties, but none singly can perform on a par with those of the Triticeae taxa, particularly the triticum species...
that are crosslinked to tTG are able to stimulate transglutaminase specific B-cell responses that eventually result in the production of ATA IgA and IgG.
Recent studies suggest that tTG plays a role in inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
, degenerative diseases, and tumor biology.
Diagnostic use
SerologySerology
Serology is the scientific study of blood serum and other bodily fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...
for anti-tTG antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
has superseded older serological tests (anti-endomysium, anti-gliadin, and anti-reticulin) and has a strong sensitivity (99%) and specificity (>90%) for identifying coeliac disease. Modern anti-tTG assays rely on a human recombinant protein as an antigen
Therapeutic use
Use of tTG as a form of surgical glue is still experimental. It is also being studied as an attenuator of metastasisMetastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
in certain tumors.
| Mouse Mutant Alleles for Tgm2 | ||
|---|---|---|
| Marker Symbol for Mouse Gene. This symbol is assigned to the genomic locus by the MGI | Tgm2 | |
| Mutant Mouse Embryonic Stem Cell Clones. These are the known targeted mutations for this gene in a mouse. | Tgm2tm1a(KOMP)Wtsi | |
| Example structure of targeted conditional mutant allele for this gene | ||
wtsi.jpg) | ||
| These Mutant ES Cells can be studied directly or used to generate mice with this gene knocked out. Study of these mice can shed light on the function of Tgm2: see Knockout mouse Knockout mouse A knockout mouse is a genetically engineered mouse in which researchers have inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA... | ||
External links
- Endomysial antibodies
- A collection of substrates and interaction partners of TG2 is accessible in the TRANSDAB, an interactive transglutaminase substrate database.