TGM2 Human
Description
Biological Functions
TGM2 exhibits enzymatic and non-enzymatic activities across intracellular and extracellular compartments:
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Crosslinking: Forms ε-(γ-glutamyl)lysine bonds between proteins, enhancing resistance to proteolysis .
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Deamidation: Converts glutamine to glutamic acid in peptides, implicated in celiac disease pathogenesis .
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GTPase Activity: Regulates intracellular signaling pathways .
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Apoptosis Modulation: Stabilizes cytoskeletal proteins during programmed cell death .
Role in Cancer
TGM2 is overexpressed in multiple cancers and correlates with poor prognosis. Key mechanisms include:
Cancer Type-Specific Mechanisms
Therapeutic Targeting
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Inhibitors: LDN27219 and Tyrphostin reduce CRC cell proliferation by reactivating p53 .
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Preclinical Outcomes: TGM2 knockdown in xenograft models slows tumor growth by 80% .
Clinical Relevance
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Prognostic Marker: Elevated TGM2 in tumors predicts advanced stages and resistance to therapy in colorectal, ovarian, and pancreatic cancers .
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Immune Modulation: In melanoma, TGM2 expression correlates with immune activation markers (e.g., CD8+ T cells), suggesting dual roles in tumor immunity .
Research Advancements
Recent studies highlight TGM2’s epigenetic roles, including histone monoaminylation, which may regulate oncogene expression . Additionally, its interaction with ERp57 in endothelial cells suggests redox regulation of extracellular activity .
Product Specs
Protein gamma-glutamyltransferase 2, EC 2.3.2.13, Tissue transglutaminase, TGase C, TGC, TG(C), Transglutaminase-2, TGase-H, TG2, TGM2.
Q&A
Here’s a structured collection of FAQs tailored to academic research on TGM2 (Transglutaminase 2), incorporating methodological insights and data from diverse studies:
What are the primary functional roles of TGM2 in human cells?
TGM2 exhibits dual enzymatic and non-enzymatic functions:
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Enzymatic: Calcium-dependent transamidation, GTP/ATP hydrolysis, and protein cross-linking .
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Non-enzymatic: Scaffolding interactions with fibronectin, regulation of mitochondrial function, and modulation of apoptosis .
Methodological note: Use activity assays (e.g., fluorescent cadaverine incorporation) paired with GTP-binding assays to distinguish enzymatic vs. signaling roles .
Which diseases are strongly linked to dysregulated TGM2 expression?
What are standard methods to detect TGM2 expression in tissues?
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Immunohistochemistry (IHC): Validated in colorectal cancer tissues (99% specificity in tumor vs. normal) .
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Western blot: Use antibodies targeting the N-terminal domain to avoid cross-reactivity with other transglutaminases .
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Activity assays: Measure transamidase activity using fluorescent substrates in Ca²⁺-buffered conditions .
How does TGM2 regulate cancer stem cell (CSC) maintenance in colorectal cancer?
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Mechanism: TGM2 promotes EMT via β-catenin stabilization and N-cadherin upregulation .
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Experimental design:
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Isolate CD133⁺ CSCs using FACS.
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Knockdown TGM2 via siRNA (≥70% efficiency required for phenotypic effects).
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Assess stemness markers (SOX2, CD133) and metastatic markers (vimentin, E-cadherin) .
Key contradiction: While TGM2 is pro-tumorigenic in CRC, its role in other cancers (e.g., breast) may be context-dependent due to stromal interactions .
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How to reconcile TGM2 knockout mouse phenotypes with human disease associations?
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Mouse data: TGM2⁻/⁻ mice show no baseline phenotype but exhibit reduced stress resilience .
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Human relevance: No homozygous loss-of-function variants reported, suggesting purifying selection .
Methodological implication: Use conditional knockout models or human organoids to study compensatory mechanisms in disease contexts.
What experimental models best capture TGM2’s role in autoimmune antigen presentation?
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In vitro: Stimulate medullary thymic epithelial cells (mTECs) with IL-1β/IFN-γ to mimic inflammatory TGM2 induction .
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In vivo: Compare NOD vs. C57BL/6 mice for thymic TGM2 expression and antigen presentation .
Critical parameter: Quantify deamidated peptide load via mass spectrometry in target tissues .
How to address contradictory findings on TGM2’s role in cancer progression?
What controls are essential when studying TGM2 enzymatic activity?
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Negative controls: EDTA (chelates Ca²⁺) or irreversible inhibitors (e.g., NC9) to confirm activity dependence .
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Positive controls: Recombinant TGM2 (≥95% purity) for assay standardization .
Why are pharmacological inhibitors of TGM2 not yet clinically viable?
Product Science Overview
Tissue transglutaminase (tTG), also known as transglutaminase 2 (TG2), is an enzyme that plays a crucial role in various biological processes, including cell adhesion, extracellular matrix assembly, and wound healing . It is widely expressed in human tissues such as the skin, liver, and jejunal mucosa . Recombinant human tissue transglutaminase (rh-tTG) is a form of this enzyme that is produced through recombinant DNA technology, allowing for its use in research and clinical applications.
Tissue transglutaminase is best known for its role as the autoantigen in celiac disease, a chronic autoimmune disorder triggered by the ingestion of gluten . In individuals with celiac disease, the immune system mistakenly targets tTG, leading to inflammation and damage to the small intestine . Beyond celiac disease, tTG has been implicated in the pathophysiology of various other conditions, including different cancers and neurodegenerative diseases .
Recombinant human tissue transglutaminase is typically produced using mammalian cell lines, such as the human embryonic kidney cell line 293-EBNA . The enzyme is expressed as a C-terminal fusion protein with a tag (e.g., Strep-tag II) that facilitates its purification via affinity chromatography . This method ensures that the recombinant enzyme retains its activity and can be used for various biochemical assays and diagnostic tests.
Tissue transglutaminase catalyzes the formation of covalent bonds between glutamine residues and primary amines, a process known as transamidation . This reaction is essential for the cross-linking of proteins, which contributes to the stability and integrity of the extracellular matrix . In the context of celiac disease, tTG modifies gluten peptides, making them more immunogenic and triggering an autoimmune response .
Recombinant human tissue transglutaminase is used in various research and clinical applications. For instance, it is employed in enzyme-linked immunosorbent assays (ELISAs) to diagnose gluten-sensitive enteropathy (GSE), including celiac disease and dermatitis herpetiformis . These assays detect antibodies against tTG in patient sera, providing a non-invasive and reliable diagnostic tool .
