Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Atlas of Genetics and Cytogenetics in Oncology and Haematology INIST-CNRS OPEN ACCESS JOURNAL Gene Section Short Communication TGM2 (transglutaminase 2) Lisa Dyer Departments of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida, USA (LD) Published in Atlas Database: November 2013 Online updated version : http://AtlasGeneticsOncology.org/Genes/TGM2ID44078ch20q11.html DOI: 10.4267/2042/53768 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2014 Atlas of Genetics and Cytogenetics in Oncology and Haematology Abstract Localisation Short Communication on TGM2, with data on DNA/RNA, on the protein encoded and where the gene is implicated. Mostly intracellular (cytosol, nucleus and cell membrane); extracellular. Identity Multifunctional enzyme with transglutaminase crosslinking activity (catalyze covalant bonds between the ε-amino group of a lysine and the γcarboxyl 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. Function Other names: G-ALPHA-h, GNAH, TG2, TGC HGNC (Hugo): TGM2 Location: 20q11.23 DNA/RNA Description The gene encompasses 36838bp; 13 exons; a dense CpG island engulfs exon 1 and the transcriptional start site; negative strand. Mutations Transcription Germinal Two transcript variants 1) 3937bp; 2) 2326bp (Cterminal truncation exons 11-13); induced by NFkB, retinoic acid, IL-6, TGF-beta1, HRE, AP-1 and GRE. 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). Protein Description 687 amino acids; 78 kilodaltons; monomer. Expression Ubiquitously expressed. Atlas Genet Cytogenet Oncol Haematol. 2014; 18(6) 397 TGM2 (transglutaminase 2) Dyer L Implicated in References Breast cancer Bernassola F, Federici M, Corazzari M, Terrinoni A, Hribal ML, De Laurenzi V, Ranalli M, Massa O, Sesti G, McLean WH, Citro G, Barbetti F, Melino G. Role of transglutaminase 2 in glucose tolerance: knockout mice studies and a putative mutation in a MODY patient. FASEB J. 2002 Sep;16(11):1371-8 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. Mehta K, Fok J, Miller FR, Koul D, Sahin AA. Prognostic significance of tissue transglutaminase in drug resistant and metastatic breast cancer. Clin Cancer Res. 2004 Dec 1;10(23):8068-76 Porzio O, Massa O, Cunsolo V, Colombo C, Malaponti M, Bertuzzi F, Hansen T, Johansen A, Pedersen O, Meschi F, Terrinoni A, Melino G, Federici M, Decarlo N, Menicagli M, Campani D, Marchetti P, Ferdaoussi M, Froguel P, Federici G, Vaxillaire M, Barbetti F. 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. Hum Mutat. 2007 Nov;28(11):1150 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. Satpathy M, Cao L, Pincheira R, Emerson R, Bigsby R, Nakshatri H, Matei D. Enhanced peritoneal ovarian tumor dissemination by tissue transglutaminase. Cancer Res. 2007 Aug 1;67(15):7194-202 Verma A, Mehta K. Tissue transglutaminase-mediated chemoresistance in cancer cells. Drug Resist Updat. 2007 Aug-Oct;10(4-5):144-51 Pancreatic cancer Prognosis Overall survival of stage II pancreatic ductal adenocarcinoma (PDAC) patients with TG2mediated 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. Ai L, Kim WJ, Demircan B, Dyer LM, Bray KJ, Skehan RR, Massoll NA, Brown KD. The transglutaminase 2 gene (TGM2), a potential molecular marker for chemotherapeutic drug sensitivity, is epigenetically silenced in breast cancer. Carcinogenesis. 2008 Mar;29(3):510-8 Cao L, Petrusca DN, Satpathy M, Nakshatri H, Petrache I, Matei D. Tissue transglutaminase protects epithelial ovarian cancer cells from cisplatin-induced apoptosis by promoting cell survival signaling. Carcinogenesis. 2008 Oct;29(10):1893-900 Non-small cell lung cancer (NSCLC) Hwang JY, Mangala LS, Fok JY, Lin YG, Merritt WM, Spannuth WA, Nick AM, Fiterman DJ, Vivas-Mejia PE, Deavers MT, Coleman RL, Lopez-Berestein G, Mehta K, Sood AK. Clinical and biological significance of tissue transglutaminase in ovarian carcinoma. Cancer Res. 2008 Jul 15;68(14):5849-58 Prognosis In 429 Korean patients, TG2 expression was associated with shorter disease free survival and correlated with recurrence. Oncogenesis Overexpression ; cisplatin resistance. Verma A, Guha S, Diagaradjane P, Kunnumakkara AB, Sanguino AM, Lopez-Berestein G, Sood AK, Aggarwal BB, Krishnan S, Gelovani JG, Mehta K. Therapeutic significance of elevated tissue transglutaminase expression in pancreatic cancer. Clin Cancer Res. 2008 Apr 15;14(8):2476-83 Celiac disease Autoantibodies against TG2; autoantibodies are deposited in the small-bowl mucosa; TG2 crosslinks gliadin peptides (gluten) derived. Atlas Genet Cytogenet Oncol Haematol. 2014; 18(6) Shao M, Cao L, Shen C, Satpathy M, Chelladurai B, Bigsby RM, Nakshatri H, Matei D. Epithelial-tomesenchymal transition and ovarian tumor progression 398 TGM2 (transglutaminase 2) Dyer L induced by tissue transglutaminase. Cancer Res. 2009 Dec 15;69(24):9192-201 Ai L, Skehan RR, Saydi J, Lin T, Brown KD. AtaxiaTelangiectasia, Mutated (ATM)/Nuclear Factor κ light chain enhancer of activated B cells (NFκB) signaling controls basal and DNA damage-induced transglutaminase 2 expression. J Biol Chem. 2012 May 25;287(22):18330-41 Lindfors K, Mäki M, Kaukinen K. Transglutaminase 2targeted autoantibodies in celiac disease: Pathogenetic players in addition to diagnostic tools? Autoimmun Rev. 2010 Sep;9(11):744-9 Király R, Barta E, Fésüs L. Polymorphism of transglutaminase 2: unusually low frequency of genomic variants with deficient functions. Amino Acids. 2013 Jan;44(1):215-25 Park KS, Kim HK, Lee JH, Choi YB, Park SY, Yang SH, Kim SY, Hong KM. Transglutaminase 2 as a cisplatin resistance marker in non-small cell lung cancer. J Cancer Res Clin Oncol. 2010 Apr;136(4):493-502 This article should be referenced as such: Choi CM, Jang SJ, Park SY, Choi YB, Jeong JH, Kim DS, Kim HK, Park KS, Nam BH, Kim HR, Kim SY, Hong KM. Transglutaminase 2 as an independent prognostic marker for survival of patients with non-adenocarcinoma subtype of non-small cell lung cancer. Mol Cancer. 2011 Sep 24;10:119 Atlas Genet Cytogenet Oncol Haematol. 2014; 18(6) Dyer L. TGM2 (transglutaminase 2). Atlas Cytogenet Oncol Haematol. 2014; 18(6):397-399. 399 Genet