Tissue transglutaminase (abbreviated as
TG2 or
tTG) is an
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
of the
transglutaminaseTransglutaminases 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
proteinProteins are organic compounds made of amino acids arranged in a linear chain and folded into a globular form. The amino acids in a polymer chain are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues...
s between an ε-amino group of a lysine residue and a γ-carboxamide group of
glutamineGlutamine is one of the 20 amino acids encoded by the standard genetic code. Its side chain is an amide formed by replacing the side-chain hydroxyl of glutamic acid with an amine functional group. It can therefore be considered the amide of glutamic acid. Its codons are CAA and CAG. Glutamine is...
residue, creating an inter- or intramolecular bond that is highly resistant to
proteolysisProteolysis 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
autoantigenAutoimmunity 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 diseaseCoeliac disease is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward. Symptoms include chronic diarrhoea, failure to thrive , and fatigue, but these may be absent, and symptoms in other organ systems have been described...
, but is also known to play a role in
apoptosisApoptosis is the process of programmed cell death that may occur in multicellular organisms. Programmed cell death involves a series of biochemical events leading to a characteristic cell morphology and death; in more specific terms, a series of biochemical events that lead to a variety of...
,
cellular differentiationIn 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 single zygote to a complex system of...
and
matrixIn 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.
tTG is expressed ubiquitously.
Tissue transglutaminase (abbreviated as
TG2 or
tTG) is an
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
of the
transglutaminaseTransglutaminases 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
proteinProteins are organic compounds made of amino acids arranged in a linear chain and folded into a globular form. The amino acids in a polymer chain are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues...
s between an ε-amino group of a lysine residue and a γ-carboxamide group of
glutamineGlutamine is one of the 20 amino acids encoded by the standard genetic code. Its side chain is an amide formed by replacing the side-chain hydroxyl of glutamic acid with an amine functional group. It can therefore be considered the amide of glutamic acid. Its codons are CAA and CAG. Glutamine is...
residue, creating an inter- or intramolecular bond that is highly resistant to
proteolysisProteolysis 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
autoantigenAutoimmunity 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 diseaseCoeliac disease is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward. Symptoms include chronic diarrhoea, failure to thrive , and fatigue, but these may be absent, and symptoms in other organ systems have been described...
, but is also known to play a role in
apoptosisApoptosis is the process of programmed cell death that may occur in multicellular organisms. Programmed cell death involves a series of biochemical events leading to a characteristic cell morphology and death; in more specific terms, a series of biochemical events that lead to a variety of...
,
cellular differentiationIn 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 single zygote to a complex system of...
and
matrixIn 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 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 acidRetinoic acid is the oxidized form of Vitamin A, with only partial vitamin A function. It functions in determining position along embryonic anterior/posterior axis in chordates...
. Amongst its many supposed functions, it appears to play a role in
wound healingWound healing, or wound repair, is an intricate process in which the skin repairs itself after injury.[Nguyen, D.T., Orgill D.P., Murphy G.F. . Chapter 4: The pathophysiologic basis for wound healing and cutaneous regeneration. Biomaterials For Treating Skin Loss. CRC Press &...]
,
apoptosisApoptosis is the process of programmed cell death that may occur in multicellular organisms. Programmed cell death involves a series of biochemical events leading to a characteristic cell morphology and death; in more specific terms, a series of biochemical events that lead to a variety of...
and
extracellular matrixIn 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
GTPaseGTPases 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. Beside 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 diseaseCoeliac disease is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward. Symptoms include chronic diarrhoea, failure to thrive , and fatigue, but these may be absent, and symptoms in other organ systems have been described...
.
Role in disease
Tissue transglutaminase is best known for its link with
coeliac diseaseCoeliac disease is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward. Symptoms include chronic diarrhoea, failure to thrive , and fatigue, but these may be absent, and symptoms in other organ systems have been described...
.
Anti-transglutaminase antibodiesAnti-transglutaminase antibodies are antibodies found more frequently in certain autoimmune diseases. High levels of ATA are found in almost all instances of coeliac disease...
(ATA) result in a form of
gluten sensitivityGluten sensitivity encompasses a collection of medical conditions in which gluten has an adverse effect. For individuals with gluten-sensitive enteropathy, removal of gluten generally results in the restoration of villus architecture or lower lymphocyte densities in the intestine...
in which a cellular response to
Triticeae glutensTriticeae 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
inflammationInflammation is 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 as well as initiate the healing process for the tissue. Inflammation is not a...
, degenerative diseases and tumor biology.
Diagnostic use
SerologySerology is the scientific study of blood serum. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...
for anti-tTG
antibodiesAntibodies are gamma globulin proteins that are found in blood or other bodily fluids of vertebrates, and are used by the immune system to identify and neutralize foreign objects, such as bacteria and viruses...
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 , or metastatic disease, sometimes abbreviated mets, is the spread of a disease from one organ or part to another non-adjacent organ or part...
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 |
|
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 |
External links
- Endomysial antibodies
- A collection of substrates and interaction partners of TG2 is accessible in the TRANSDAB, an interactive transglutaminase substrate database.