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FLASH GENE
Symbol TGM2 contributors: mct/pgu - updated : 16-05-2018
HGNC name transglutaminase 2 (C polypeptide, protein-glutamine-gamma-glutamyltransferase)
HGNC id 11778
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularvessel   moderately Homo sapiens
Nervousbrain   highly Homo sapiens
Reproductivefemale systemplacenta  highly
 female systemuterus  highly
Respiratorylung   highly
 respiratory tracttrachea  highly
Urinarykidney   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow  moderately
Connectiveadipose  moderately
Muscularsmoothvessel   Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Cardiovascularendothelial cell Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal
Text umbilical cord at a predominantly level
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a transglutaminase site activity
  • C-terminal GTP-binding domain is important in stabilizing and promoting the half-life of TGM2
  • conjugated PhosphoP
    mono polymer monomer
    HOMOLOGY
    interspecies homolog to rattus Tgm2 (83.24 pc)
    homolog to murine Tgm2 (84.26 pc)
    Homologene
    FAMILY
  • transglutaminase superfamily
  • transglutaminase-like family
  • CATEGORY enzyme , tumor suppressor
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    text
  • extracellular matrix protein
  • colocalized with COL18A1 in the extracellular matrix, secreted by endothelial cells under hypoxia, which stimulates angiogenesis
  • basic FUNCTION
  • catalyzing the cross linking of proteins by epsilon-gamma glutamyl lysine isopeptide bonds
  • may be involved in apoptosis
  • involved in several steps of wound healing
  • inhibits in cooperation with GPR56 melanoma tumor growth and metastasis
  • involved in corneal epithelial cell death after UVB
  • play an important role in controlling the deformability and fragility, and therefore lifespan of erythrocytes, in a number of pathophysiological situations
  • involved in signal transduction and, like two other TGs (TGM3 and TGM5), is able to bind and hydrolyze guanosine triphosphate
  • multifunctional enzyme that has been implicated in the pathogenesis of neurodegenerative diseases, ischemia, and stroke
  • may play an important role in protecting against the delayed neuronal cell death in ischemia and stroke
  • may be involved in the development of schizophrenia
  • antiapoptotic mediator of HIF1A through modulating both apoptosis and survival pathways that may confer a selective growth advantage to tumor cells
  • inhibits CASP3 activity and activates NFKB1 pathway
  • involved in early onset diabetes type 2
  • regulates levels of cellular GTP-bound Rac and actin cytoskeletal reorganization through direct inhibition of BcR GTP-ase activating activity
  • increased TGM2 expression can result in the induction of TGFB1 causing increased synthesis and deposition of matrix proteins
  • acts as a G-protein
  • inducing degradation of PP2A-alpha, thereby increasing MMP2 transcription
  • important extracellular crosslinking enzyme involved in matrix turnover and in bone differentiation
  • in vascular SMCs acts as a principal enhancer within the PDGF-BB/PDGFRB signaling axis involved in phenotypic modulation of these cells, thereby suggesting a novel role in the progression of vascular diseases
  • directly regulates hypoxic transcriptional machinery, but its interaction with HIF1B was not required for this regulation
  • may have intrinsic kinase activity that phosphorylates paxillin
  • roles of TGM2 in ADGRG1-mediated melanoma inhibition
  • is a calcium-dependent enzyme that irreversibly modifies proteins by forming cross-linked protein aggregates
  • because stress events activate the sympathetic nervous system and result in secretion of the catecholamines, adrenoceptor-mediated increase in macrophage TGM2 expression might be associated with stress-related inflammatory disorders
  • multifunctional protein cross-linking enzyme that has been implicated in apoptotic cell clearance but is also important in many other cell functions including cell adhesion, migration and monocyte to macrophage differentiation
  • expressed in mast cells recruited into skin or bone marrow, induces the development of pediatric mastocytosis
  • TGM2, likely in association with heparan sulphates, may exert its effect on apoptotic cell clearance via a mechanism involving the crosslinking of CD44
  • is an important player in the biogenesis of exosomes controlling the selectivity of their cargo under stressful cellular conditions
  • catalyzes a crosslink between protein bound-glutamine and -lysine
  • multifunctional enzyme tissue Transglutaminase (TGM2) is known to participate in most of the monocyte- and macrophage-mediated processes
  • ubiquitous crosslinking enzyme present in both intra- and extracellular in many cell types and tissues
  • TGM2 functions include transamidation and GTPase activity, among others, and is implicated as a regulator of astrocytes migration
  • might contribute to early hepato-cellular carcinoma (HCC) recurrence through signaling pathways not related to epithelial-mesenchymal transition (EMT) and integrin signaling 9)
  • kidney fibrosis in aging may represent a natural outcome of upregulated COL18A1 and TGM2, but more likely it appears to be a result of cumulative stresses occurring on the background of synergistically acting geronic (aging) proteins, COL18A1 and TGM2
  • TGM2 is involved in a broad range of cellular processes (including transmembrane signaling, mitochondrial functions, gene expression regulation, autophagy, and apoptosis)
  • has a pivotal role in celiac disease pathogenesis through generating immunogenic peptides from gliadin
  • TGM2 (and possibly also TGM3, TGM7) gained vital functions which have not been fully revealed, yet
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • PKM/TGM2 interplay plays an important role in the regulation of autophagy in particular under cellular stressful conditions such as those displayed by cancer cells
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
  • protein
  • interacting with huntingtin
  • ligand of GPR56 (cooperating in the suppressive role of GPR56)
  • TNFR1 and CASP3 activation
  • interaction with COL18A1 might participate in the concerted regulation of angiogenesis and tumorigenesis by COL18A1 and TGM2
  • HIF1B is a TGM2 binding partner
  • bound to the Rac-binding pocket in the GTPase-activating domains of BCR and ABR, blocked BCR activity and, through this mechanism, increased levels of active GTP-bound Rac and EGF-stimulated membrane ruffling
  • interacting with SDC4
  • TXN is a highly specific activator of oxidized human TGM2
  • SERPINB2 and TGM2 are downstream mediators in the antiapoptotic response triggered upon TBK1 activation
  • direct link between TGM2, NFKB1, and HIF1A, demonstrating TGM2 important role in cancer progression
  • activates CTNNB1 signaling in vascular smooth muscle cells (VSMCs)
  • TGM2 binds directly to the extracellular domain of LRP6, which is also able to act as a substrate for TGM2-mediated protein cross-linking
  • SPP1 can be polymerized by the cross-linking enzyme transglutaminase 2 (TGM2), and polymerization has been shown to enhance the biological activity of SPP1
  • TGM2-SDC4 interaction through heparan sulphate side chains, and knockdown of SDC4 reduces cell surface TGM2 activity and apoptotic cell clearance
  • TGM2 interacts with PKM, a rate limiting enzyme of glycolysis which is responsible for maintaining a glycolytic phenotype in malignant cells and displays non metabolic functions, including transcriptional co-activation and protein kinase activity
  • TGM2-mediated autophagy and CDKN1A-mediated cell cycle arrest are two important barriers in the TP53 pathway that prevent oncogenic transformation
  • COL18A1 is an interactive partner of transglutaminase 2 (TGM2), an enzyme that cross-links extracellular matrix proteins
  • is involved in cell-matrix interactions through association with the extracellular matrix protein, fibronectin (FN1)
  • binding of TGM2 to the ECM of small intestinal tissue sections is the sum of binding to FN1 via its N-terminal domain and binding to an abundant, novel extracellular matrix (ECM) interaction partner via its second C-terminal beta-barrel domain
  • cell & other
    REGULATION
    activated by hypoxia
    induced by by retinoic acid
    Other induction of TGM2 by RAR alpha pathway increases the clearance of apoptotic cells by macrophages
    nitric oxide may regulate TGM2 function in the extracellular environment
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    overexpressed in ovarian cancer and promoting intraperitoneal metastasis
    constitutional     --over  
    overexpressed in cystic fibrosis and affecting NDPK function
    constitutional     --over  
    in neurons exposed to oxygen and glucose deprivation (OGD), and increased TGM2 expression protects neurons against OGD-induced cell death independent of its transamidating activity
    Susceptibility
  • to schizophrenia
  • Variant & Polymorphism
    Candidate gene
    Marker
  • can serve as a biomarker for all grades of cervical dysplasia
  • may be used in diagnosis of pediatric mastocytosis, particularly systemic mastocytosis (SM)
  • Therapy target
    SystemTypeDisorderPubmed
    cancer  
    inhibition of TGM2 may offer a novel strategy for anticancer therapy
    cancermetastases 
    inhibiting TGM2 may offer a novel therapeutic approach for managing and treatment of metastatic cancer
    cardiovascularaquired 
    is a potential therapeutic target for blocking neointima in blood vessels
    ANIMAL & CELL MODELS
  • glucose homeostasis in mice is Tgm2 independent