Download Gene Section TGM2 (transglutaminase 2) Atlas of Genetics and Cytogenetics

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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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.
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