TGM2 (transglutaminase 2)

2013-11-01   Lisa Dyer 

Departments 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

Atlas Image

Description

The gene encompasses 36838bp; 13 exons; a dense CpG island engulfs exon 1 and the transcriptional start site; negative strand.

Transcription

Two transcript variants 1) 3937bp; 2) 2326bp (C-terminal truncation exons 11-13); induced by NFkB, retinoic acid, IL-6, TGF-beta1, HRE, AP-1 and GRE.

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.

Bibliography

Pubmed IDLast YearTitleAuthors
181742472008The transglutaminase 2 gene (TGM2), a potential molecular marker for chemotherapeutic drug sensitivity, is epigenetically silenced in breast cancer.Ai L et al
224932842012Ataxia-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
122050282002Role of transglutaminase 2 in glucose tolerance: knockout mice studies and a putative mutation in a MODY patient.Bernassola F et al
186674462008Tissue transglutaminase protects epithelial ovarian cancer cells from cisplatin-induced apoptosis by promoting cell survival signaling.Cao L et al
219431222011Transglutaminase 2 as an independent prognostic marker for survival of patients with non-adenocarcinoma subtype of non-small cell lung cancer.Choi CM et al
186326392008Clinical and biological significance of tissue transglutaminase in ovarian carcinoma.Hwang JY et al
221602622013Polymorphism of transglutaminase 2: unusually low frequency of genomic variants with deficient functions.Király R et al
205472482010Transglutaminase 2-targeted autoantibodies in celiac disease: Pathogenetic players in addition to diagnostic tools?Lindfors K et al
155856422004Prognostic significance of tissue transglutaminase in drug resistant and metastatic breast cancer.Mehta K et al
197636202010Transglutaminase 2 as a cisplatin resistance marker in non-small cell lung cancer.Park KS et al
179391762007Missense 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
176711872007Enhanced peritoneal ovarian tumor dissemination by tissue transglutaminase.Satpathy M et al
199519932009Epithelial-to-mesenchymal transition and ovarian tumor progression induced by tissue transglutaminase.Shao M et al
184138402008Therapeutic significance of elevated tissue transglutaminase expression in pancreatic cancer.Verma A et al
176626452007Tissue 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 IDTranscript IDUniprot
ENSG00000198959ENST00000361475P21980
ENSG00000198959ENST00000361475V9HWG3
ENSG00000198959ENST00000373403A2A299
ENSG00000198959ENST00000453095A2A2A0

Expression (GTEx)

0
500
1000
1500
2000

Pathways

PathwaySourceExternal ID
Huntington's diseaseKEGGko05016
Huntington's diseaseKEGGhsa05016

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
180928892007Transglutaminase 2 undergoes a large conformational change upon activation.145
219638462012Tissue transglutaminase links TGF-β, epithelial to mesenchymal transition and a stem cell phenotype in ovarian cancer.89
169511952006Overexpression of tissue transglutaminase leads to constitutive activation of nuclear factor-kappaB in cancer cells: delineation of a novel pathway.88
167575642006GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis.87
223648712012Cellular functions of tissue transglutaminase.75
170436482007Tissue transglutaminase expression promotes cell attachment, invasion and survival in breast cancer cells.68
205477692010Redox regulation of transglutaminase 2 activity.64
223669522012High abundance of plasma cells secreting transglutaminase 2-specific IgA autoantibodies with limited somatic hypermutation in celiac disease intestinal lesions.64
155856422004Prognostic significance of tissue transglutaminase in drug resistant and metastatic breast cancer.63
209672282010Tissue transglutaminase promotes drug resistance and invasion by inducing mesenchymal transition in mammary epithelial cells.55

Citation

Lisa Dyer

TGM2 (transglutaminase 2)

Atlas Genet Cytogenet Oncol Haematol. 2013-11-01

Online version: http://atlasgeneticsoncology.org/gene/44078/tgm2-(transglutaminase-2)