Mouse Anti-Tgm2 Recombinant Antibody (CBYJT-2853) (CBMAB-T2079-YJ)

TGM2 Gene(Protein Coding) Transglutaminase 2

Tgm2 catalyzes acyl transferase reaction of gamma-carboxamide groups of glutamine residues (donor peptide) with epsilon-amino groups of lysine residues (acceptor peptide).

Calcium-dependent acyltransferase that catalyzes the formation of covalent bonds between peptide-bound glutamine and various primary amines, such as gamma-amino group of peptide-bound lysine, or mono- and polyamines, thereby producing cross-linked or aminated proteins, respectively (PubMed:9252372, PubMed:23941696, PubMed:31991788).
Involved in many biological processes, such as bone development, angiogenesis, wound healing, cellular differentiation, chromatin modification and apoptosis (PubMed:1683874, PubMed:7935379, PubMed:9252372, PubMed:27270573).
Acts as a protein-glutamine gamma-glutamyltransferase by mediating the cross-linking of proteins, such as ACO2, HSPB6, FN1, HMGB1, RAP1GDS1, SLC25A4/ANT1, SPP1 and WDR54 (PubMed:23941696, PubMed:24349085, PubMed:29618516, PubMed:30458214).
Under physiological conditions, the protein cross-linking activity is inhibited by GTP; inhibition is relieved by Ca2+ in response to various stresses (PubMed:7649299, PubMed:7592956, PubMed:18092889).
When secreted, catalyzes cross-linking of proteins of the extracellular matrix, such as FN1 and SPP1 resulting in the formation of scaffolds (PubMed:12506096).
Plays a key role during apoptosis, both by 1 promoting the cross-linking of cytoskeletal proteins resulting in condensation of the cytoplasm, and by 2 mediating cross-linking proteins of the extracellular matrix, resulting in the irreversible formation of scaffolds that stabilize the integrity of the dying cells before their clearance by phagocytosis, thereby preventing the leakage of harmful intracellular components (PubMed:7935379, PubMed:9252372).
In addition to protein cross-linking, can use different monoamine substrates to catalyze a vast array of protein post-translational modifications: mediates aminylation of serotonin, dopamine, noradrenaline or histamine into glutamine residues of target proteins to generate protein serotonylation, dopaminylation, noradrenalinylation or histaminylation, respectively (PubMed:23797785, PubMed:30867594).
Mediates protein serotonylation of small GTPases during activation and aggregation of platelets, leading to constitutive activation of these GTPases (By similarity).
Plays a key role in chromatin organization by mediating serotonylation and dopaminylation of histone H3 (PubMed:30867594, PubMed:32273471).
Catalyzes serotonylation of 'Gln-5' of histone H3 (H3Q5ser) during serotonergic neuron differentiation, thereby facilitating transcription (PubMed:30867594).
Acts as a mediator of neurotransmission-independent role of nuclear dopamine in ventral tegmental area (VTA) neurons: catalyzes dopaminylation of 'Gln-5' of histone H3 (H3Q5dop), thereby regulating relapse-related transcriptional plasticity in the reward system (PubMed:32273471).
Regulates vein remodeling by mediating serotonylation and subsequent inactivation of ATP2A2/SERCA2 (By similarity).
Also acts as a protein deamidase by mediating the side chain deamidation of specific glutamine residues of proteins to glutamate (PubMed:9623982, PubMed:20547769).
Catalyzes specific deamidation of protein gliadin, a component of wheat gluten in the diet (PubMed:9623982).
May also act as an isopeptidase cleaving the previously formed cross-links (PubMed:26250429, PubMed:27131890).
Also able to participate in signaling pathways independently of its acyltransferase activity: acts as a signal transducer in alpha-1 adrenergic receptor-mediated stimulation of phospholipase C-delta (PLCD) activity and is required for coupling alpha-1 adrenergic agonists to the stimulation of phosphoinositide lipid metabolism (PubMed:8943303).
Isoform 2
Has cytotoxic activity: is able to induce apoptosis independently of its acyltransferase activity.

Biological Process apoptotic cell clearanceSource:UniProtKB1 Publication
Biological Process bone developmentSource:UniProtKB
Biological Process branching involved in salivary gland morphogenesisSource:Ensembl
Biological Process cellular response to cocaineSource:UniProtKB1 Publication
Biological Process cellular response to dopamineSource:UniProtKB1 Publication
Biological Process cellular response to serotoninSource:UniProtKB1 Publication
Biological Process negative regulation of endoplasmic reticulum calcium ion concentrationSource:UniProtKB1 Publication
Biological Process peptide cross-linkingSource:UniProtKB4 Publications
Biological Process phospholipase C-activating G protein-coupled receptor signaling pathwaySource:UniProtKB2 Publications
Biological Process positive regulation of apoptotic processSource:UniProtKB1 Publication
Biological Process positive regulation of cell adhesionSource:UniProtKB
Biological Process positive regulation of GTPase activitySource:UniProtKB
Biological Process positive regulation of mitochondrial calcium ion concentrationSource:UniProtKB1 Publication
Biological Process positive regulation of neurogenesisSource:UniProtKB1 Publication
Biological Process positive regulation of small GTPase mediated signal transductionSource:UniProtKB
Biological Process protein deaminationSource:UniProtKB2 Publications
Biological Process protein homooligomerizationSource:UniProtKB
Biological Process proteolysisSource:UniProtKB-KW
Biological Process regulation of apoptotic cell clearanceSource:UniProtKB1 Publication
Biological Process regulation of apoptotic processSource:UniProtKB1 Publication
Biological Process salivary gland cavitationSource:Ensembl

Cytoplasm, cytosol
Nucleus
Chromosome
Secreted, extracellular space, extracellular matrix
Cell membrane
Mitochondrion
Mainly localizes to the cytosol (PubMed:9575137).
Present at much lower level in the nucleus and chromatin (PubMed:9575137).
Also secreted via a non-classical secretion pathway to the extracellular matrix (PubMed:27270573).
Isoform 2
Cytoplasm, perinuclear region

TGM2 constitutes the major autoantigen in celiac disease, a multifactorial chronic disorder of the small intestine caused by intolerance to gluten (PubMed:9212111, PubMed:9623982). Celiac disease is characterized by immune-mediated enteropathy associated with failed intestinal absorption and malnutrition: intestinal inflammation is precipitated by ingestion of the protein gliadin, a component of wheat gluten in the diet (PubMed:9212111, PubMed:9623982). TGM2 is the main target for celiac disease-associated anti-endomysium autoantibodies (PubMed:9212111). It mediates its effect by catalyzing specific deamidation of gliadin; this deamidation creates an epitope that binds efficiently to HLA-DQ2 and is recognized by gut-derived T-cells (PubMed:9623982).

Disulfide bond formation inactivates the calcium-dependent acyltransferase activity (PubMed:20547769).
Cys-370 can form disulfide bonds with both Cys-230 and Cys-371: formation of a disulfide bond between Cys-230 and Cys-370 facilitates formation of the disulfide between Cys-370 and Cys-371, which promotes inactivation of the acyltransferase activity (PubMed:20547769).
May also form interchain disulfids between Cys-230 and Cys-370 (PubMed:25192068).
Ca2+ protects against disulfide bond formation and inactivation (PubMed:20547769).
Auto-transglutaminated: Forms covalent cross-links mediated by transglutaminase between Gln-633 and the epsilon-amino group of a lysine residue of itself or HMGB1, forming homopolymers and heteropolymers, respectively.
S-nitrosylated, leading to inactivation of the acyltransferase activity.