TGM2 (transglutaminase 2)
2013-11-01 Lisa Dyer AffiliationDepartments of Biochemistry, Molecular Biology, University of Florida, Gainesville, Florida, USA
Identity
HGNC
LOCATION
20q11.23
LOCUSID
ALIAS
G(h),TG(C),TGC,hTG2,tTG
FUSION GENES
DNA/RNA
Description
The gene encompasses 36838bp; 13 exons; a dense CpG island engulfs exon 1 and the transcriptional start site; negative strand.
Proteins
Description
687 amino acids; 78 kilodaltons; monomer.
Expression
Ubiquitously expressed.
Localisation
Mostly intracellular (cytosol, nucleus and cell membrane); extracellular.
Function
Multifunctional enzyme with transglutaminase crosslinking activity (catalyze covalant bonds between the ε-amino group of a lysine and the γ-carboxyl group of a glutamine residue) stabilizing the extracellular matrix (ECM) and cell-ECM interaction; require Ca2+ for catalytic activity; inhibited by GTP; under stress (loss of Ca2+) may play a role in apoptosis; involved in wound healing and inflammation ; aberrent overexpression of TG2 is linked to chemotherapeutic drug resistance.
Mutations
Germinal
No germinal mutations have been identified; low frequency of SNPs.
Somatic
No somatic mutations have been identified in cancer; can be transcriptionally silenced by CpG methylation in cancer (breast and brain); overexpression in many cancers; 3 missense mutations identified in early-onset type 2 diabetes patients (c.989T>G, c.992T>A, c.998A>G).
Implicated in
Entity name
Breast cancer
Oncogenesis
Overexpression renders culture mammary epithelial cells resistant to doxorubicin, associated with invasive phenotype and epithelial-to-mesenchymal transition; epigenetic silencing has been documented in many breast cancer cell lines and patient samples; In 30 patients, TG2 overexpression was found more often in lymph node metastases than primary tumors.
Entity name
Ovarian cancer
Prognosis
Overexpression of TG2 is associated with negative survival in 93 patients (p=0.007).
Oncogenesis
Overexpression renders ovarian cancer cells resistant to cisplatin and is associated with higher tumor stage.
Entity name
Pancreatic cancer
Prognosis
Overall survival of stage II pancreatic ductal adenocarcinoma (PDAC) patients with TG2-mediated loss of PTEN was poor (20.7 months) compared to 68.6 months for TG2 negative and PTEN positive patients.
Oncogenesis
Overexpression; resistance to gemcitabine; in 51 PDAC tumor samples overexpression of TG2 was associated with loss of PTEN expression.
Entity name
Non-small cell lung cancer (NSCLC)
Prognosis
In 429 Korean patients, TG2 expression was associated with shorter disease free survival and correlated with recurrence.
Oncogenesis
Overexpression ; cisplatin resistance.
Entity name
Celiac disease
Note
Autoantibodies against TG2 ; autoantibodies are deposited in the small-bowl mucosa; TG2 crosslinks gliadin peptides (gluten) derived.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 18174247 | 2008 | The transglutaminase 2 gene (TGM2), a potential molecular marker for chemotherapeutic drug sensitivity, is epigenetically silenced in breast cancer. | Ai L et al |
| 22493284 | 2012 | Ataxia-Telangiectasia, Mutated (ATM)/Nuclear Factor κ light chain enhancer of activated B cells (NFκB) signaling controls basal and DNA damage-induced transglutaminase 2 expression. | Ai L et al |
| 12205028 | 2002 | Role of transglutaminase 2 in glucose tolerance: knockout mice studies and a putative mutation in a MODY patient. | Bernassola F et al |
| 18667446 | 2008 | Tissue transglutaminase protects epithelial ovarian cancer cells from cisplatin-induced apoptosis by promoting cell survival signaling. | Cao L et al |
| 21943122 | 2011 | Transglutaminase 2 as an independent prognostic marker for survival of patients with non-adenocarcinoma subtype of non-small cell lung cancer. | Choi CM et al |
| 18632639 | 2008 | Clinical and biological significance of tissue transglutaminase in ovarian carcinoma. | Hwang JY et al |
| 22160262 | 2013 | Polymorphism of transglutaminase 2: unusually low frequency of genomic variants with deficient functions. | Király R et al |
| 20547248 | 2010 | Transglutaminase 2-targeted autoantibodies in celiac disease: Pathogenetic players in addition to diagnostic tools? | Lindfors K et al |
| 15585642 | 2004 | Prognostic significance of tissue transglutaminase in drug resistant and metastatic breast cancer. | Mehta K et al |
| 19763620 | 2010 | Transglutaminase 2 as a cisplatin resistance marker in non-small cell lung cancer. | Park KS et al |
| 17939176 | 2007 | Missense mutations in the TGM2 gene encoding transglutaminase 2 are found in patients with early-onset type 2 diabetes. Mutation in brief no. 982. Online. | Porzio O et al |
| 17671187 | 2007 | Enhanced peritoneal ovarian tumor dissemination by tissue transglutaminase. | Satpathy M et al |
| 19951993 | 2009 | Epithelial-to-mesenchymal transition and ovarian tumor progression induced by tissue transglutaminase. | Shao M et al |
| 18413840 | 2008 | Therapeutic significance of elevated tissue transglutaminase expression in pancreatic cancer. | Verma A et al |
| 17662645 | 2007 | Tissue transglutaminase-mediated chemoresistance in cancer cells. | Verma A et al |
Other Information
Locus ID:
NCBI: 7052
MIM: 190196
HGNC: 11778
Ensembl: ENSG00000198959
Variants:
dbSNP: 7052
ClinVar: 7052
TCGA: ENSG00000198959
COSMIC: TGM2
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000198959 | ENST00000361475 | P21980 |
| ENSG00000198959 | ENST00000361475 | V9HWG3 |
| ENSG00000198959 | ENST00000373403 | A2A299 |
| ENSG00000198959 | ENST00000453095 | A2A2A0 |
Expression (GTEx)
Pathways
| Pathway | Source | External ID |
|---|---|---|
| Huntington's disease | KEGG | ko05016 |
| Huntington's disease | KEGG | hsa05016 |
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38363884 | 2024 | Prognostic significance of RKIP, TGM2, and CMTM4 expression in oral squamous cell carcinoma. | 0 |
| 38474044 | 2024 | The Role of Transglutaminase 2 in Cancer: An Update. | 2 |
| 38667282 | 2024 | Biological Implications and Functional Significance of Transglutaminase Type 2 in Nervous System Tumors. | 1 |
| 38959038 | 2024 | Structural and mechanistic analysis of Ca(2+)-dependent regulation of transglutaminase 2 activity using a Ca(2+)-bound intermediate state. | 0 |
| 38363884 | 2024 | Prognostic significance of RKIP, TGM2, and CMTM4 expression in oral squamous cell carcinoma. | 0 |
| 38474044 | 2024 | The Role of Transglutaminase 2 in Cancer: An Update. | 2 |
| 38667282 | 2024 | Biological Implications and Functional Significance of Transglutaminase Type 2 in Nervous System Tumors. | 1 |
| 38959038 | 2024 | Structural and mechanistic analysis of Ca(2+)-dependent regulation of transglutaminase 2 activity using a Ca(2+)-bound intermediate state. | 0 |
| 35848131 | 2023 | The transglutaminase 2 cancer cell survival factor maintains mTOR activity to drive an aggressive cancer phenotype. | 2 |
| 36353796 | 2023 | Cytosolic TGM2 promotes malignant progression in gastric cancer by suppressing the TRIM21-mediated ubiquitination/degradation of STAT1 in a GTP binding-dependent modality. | 8 |
| 36695883 | 2023 | Type 2 transglutaminase in the nucleus: the new epigenetic face of a cytoplasmic enzyme. | 4 |
| 36824360 | 2023 | A long non-coding RNA that harbors a SNP associated with type 2 diabetes regulates the expression of TGM2 gene in pancreatic beta cells. | 2 |
| 37160910 | 2023 | Canonical and truncated transglutaminase-2 regulate mucin-1 expression and androgen independency in prostate cancer cell lines. | 2 |
| 37227250 | 2023 | Transglutaminase 2 Binds to the CD44v6 Cytoplasmic Domain to Stimulate CD44v6/ERK1/2 Signaling and Maintain an Aggressive Cancer Phenotype. | 1 |
| 37340285 | 2023 | Transglutaminase 2 expression is associated with increased risk of lymph node metastasis and recurrence in papillary thyroid cancer. | 0 |
Citation
Lisa Dyer
TGM2 (transglutaminase 2)
Atlas Genet Cytogenet Oncol Haematol. 2013-11-01
Online version: http://atlasgeneticsoncology.org/gene/44078/tgm2-(transglutaminase-2)
