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Tbio Glutathione peroxidase 2

Could play a major role in protecting mammals from the toxicity of ingested organic hydroperoxides. Tert-butyl hydroperoxide, cumene hydroperoxide and linoleic acid hydroperoxide but not phosphatidycholine hydroperoxide, can act as acceptors.

The protein encoded by this gene belongs to the glutathione peroxidase family, members of which catalyze the reduction of organic hydroperoxides and hydrogen peroxide (H2O2) by glutathione, and thereby protect cells against oxidative damage. Several isozymes of this gene family exist in vertebrates, which vary in cellular location and substrate specificity. This isozyme is predominantly expressed in the gastrointestinal tract (also in liver in human), is localized in the cytoplasm, and whose preferred substrate is hydrogen peroxide. Overexpression of this gene is associated with increased differentiation and proliferation in colorectal cancer. This isozyme is also a selenoprotein, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2016]

 Comments

Property Summary

NCBI Gene PubMed Count 44
PubMed Score 190.49
PubTator Score 83.40

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (3)

Disease Target Count Z-score Confidence
Cancer 2346 3.406 1.7
Inflammatory bowel disease 142 3.321 1.7

Expression

  Differential Expression (18)

Disease log2 FC p
esophageal adenocarcinoma 1.900 1.8e-02
psoriasis 1.500 2.6e-03
osteosarcoma 2.393 8.5e-08
primary pancreatic ductal adenocarcinoma 3.264 9.6e-04
non-small cell lung cancer 4.293 3.0e-15
intraductal papillary-mucinous adenoma (... 2.200 8.0e-03
intraductal papillary-mucinous carcinoma... 2.300 1.3e-02
intraductal papillary-mucinous neoplasm ... 2.300 4.4e-02
colon cancer 1.500 1.9e-02
lung cancer 6.900 5.0e-07
pancreatic cancer 3.200 1.2e-03
interstitial cystitis -3.500 1.9e-03
cystic fibrosis -1.500 1.4e-02
lung adenocarcinoma 2.100 9.0e-06
primary Sjogren syndrome -1.200 1.4e-02
non-inflammatory breast cancer -1.300 1.9e-08
lung carcinoma 2.400 1.8e-20
head and neck cancer and chronic obstruc... -1.600 2.2e-03

Synonym

Accession P18283 Q6PJ52 Q8WWI7 Q9NRP9 GPx-2
Symbols GPRP
GPx-2
GI-GPx
GPRP-2
GPx-GI
GSHPx-2
GSHPX-GI

Gene

GPX2

PANTHER Protein Class (2)

PDB

2HE3  

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG Inparanoid

 UniProt Keyword (8)

 GO Function (2)

 GO Component (3)

 GO Process (1)

 Compartment GO Term (20)

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 MGI Phenotype (6)

 HCA RNA Cell Line (48)

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Pathway (28)

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Protein-protein Interaction (1)

SOD1  

Gene RIF (35)

PMID Text
25813210 GPX2 underexpression is associated with advanced tumor status and implicated unfavorable clinical outcome of UCs, suggesting its role in tumor progression and may serve as a theranostic biomarker of UCs.
25261240 high GPx2 expression was associated with early tumor recurrence, particularly in the recently identified aggressive subtype of human colon cancer.
24562575 Patients with high GPX2 expression in biopsy specimen had significantly lower prostate-specific antigen recurrence-free survival and overall survival than those with no GPX2 expression.
23934683 miR-185 plays a role in up-regulation of GPX2 and SEPHS2 expression.
22758632 A GPx2-independent decrease in tumor development by selenium (Se) and detrimental effects of the Nrf2-activator sulforaphane in moderate Se deficiency.
22683372 A role of GPx2, TrxR2 and TrxR3 in proliferation, apoptosis and, therefore, also during cancer development.
20813000 Meta-analysis of gene-disease association. (HuGE Navigator)
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20200426 Observational study of gene-disease association. (HuGE Navigator)
19913121 Observational study of gene-disease association. (HuGE Navigator)
19884766 Glutathione peroxidase 2 (GPX2) is downregulated in HIV-1 Tat and NC cotransfection of HEK 293T cells
19773279 Observational study of gene-disease association. (HuGE Navigator)
19692168 Observational study of gene-disease association. (HuGE Navigator)
19625176 Observational study of gene-disease association. (HuGE Navigator)
19573080 Observational study of gene-disease association. (HuGE Navigator)
19170196 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
19161995 Observational study of genetic testing. (HuGE Navigator)
19047153 Data show that GPx2 inhibits malignant characteristics of tumor cells, migration and invasion, obviously by counteracting COX-2 expression but is required for the growth of transformed intestinal cells and may, therefore, facilitate tumor cell growth.
18676680 Observational study of gene-disease association. (HuGE Navigator)
18483336 No significant risk for GPX2 in colorectal adenoma.
18483336 Observational study of gene-disease association. (HuGE Navigator)
18479189 Results show that GPx2 by compartmentalized removal of hydroperoxides silences COX-2 activity and suppresses PGE(2)-dependent COX-2 and mPGES-1 expression.
18056462 Gpx2 is an overexpressed gene in human breast cancers
17937616 Activation of the glutathione peroxidase 2 (GPx2) promoter by beta-catenin.
17277236 Observational study of gene-disease association. (HuGE Navigator)
17277236 SNPs involving the GSTP1, MnSOD and GPX2 genes were not associated with Barrett's esophagus or esophageal adenocarcinoma
16794261 Glutathione peroxidase 2 (GPX2) is the major oxidative stress-inducible cellular GPX isoform in the lungs, and its basal as well as inducible expression is dependent on Nrf2.
16446369 some isoforms of p63 serve as a pro-survival factor by up-regulating GPX2 to reduce the p53-dependent oxidative stress-induced apoptotic response
15923610 Data suggest that some antioxidants may exert their anti-inflammatory and anticarcinogenic effects not only by induction of phase 2 enzymes but also by the up-regulation of the selenoprotein GI-GPx by Nrf2 binding.
15910762 Glutathione peroxidase 2 (GPX2) is downregulated in HIV-1 Tat and NC cotransfection of HEK 293T cells
12751789 Knockout studies in mice suggest that Gpx2 mRNA and GPX-2 activity levels are induced by luminal microflora, consistent with a role in suppression of inflammation in the mucosal epithelium during weaning.
11811519 Cellular and subcellular localization of gastrointestinal glutathione peroxidase in normal and malignant human intestinal tissue
11368344 Glutathione peroxidase 2 (GPX2) is downregulated in HIV-1 Tat and NC cotransfection of HEK 293T cells
10652368 Glutathione peroxidase 2 (GPX2) is downregulated in HIV-1 Tat and NC cotransfection of HEK 293T cells
9501919 Glutathione peroxidase 2 (GPX2) is downregulated in HIV-1 Tat and NC cotransfection of HEK 293T cells

AA Sequence 

MAFIAKSFYDLSAISLDGEKVDFNTFRGRAVLIENVASLUGTTTRDFTQLNELQCRFPRRLVVLGFPCNQ      1 - 70
FGHQENCQNEEILNSLKYVRPGGGYQPTFTLVQKCEVNGQNEHPVFAYLKDKLPYPYDDPFSLMTDPKLI     71 - 140
IWSPVRRSDVAWNFEKFLIGPEGEPFRRYSRTFPTINIEPDIKRLLKVAI                        141 - 190
//

Text Mined References (46)

PMID Year Title
25813210 2015 GPX2 underexpression indicates poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder.
25261240 2014 GPx2 suppression of H2O2 stress links the formation of differentiated tumor mass to metastatic capacity in colorectal cancer.
24562575 2014 GPX2 overexpression is involved in cell proliferation and prognosis of castration-resistant prostate cancer.
23934683 2013 Selenium alters miRNA profile in an intestinal cell line: evidence that miR-185 regulates expression of GPX2 and SEPSH2.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
22758632 2012 Physiological functions of GPx2 and its role in inflammation-triggered carcinogenesis.
22683372 2012 The selenoproteins GPx2, TrxR2 and TrxR3 are regulated by Wnt signalling in the intestinal epithelium.
21269460 2011 Initial characterization of the human central proteome.
20813000 2010 Polymorphisms in DNA repair genes and risk of non-Hodgkin lymphoma in a pooled analysis of three studies.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20200426 2010 Glutathione pathway genetic polymorphisms and lung cancer survival after platinum-based chemotherapy.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19773279 2009 Association between genetic variants in VEGF, ERCC3 and occupational benzene haematotoxicity.
19692168 2010 Genetic susceptibility to distinct bladder cancer subphenotypes.
19625176 2009 PTEN identified as important risk factor of chronic obstructive pulmonary disease.
19573080 2009 Common genetic variants in candidate genes and risk of familial lymphoid malignancies.
19170196 2009 Polymorphisms in innate immunity genes and lung cancer risk in Xuanwei, China.
19161995 2009 Simultaneous genotyping of 11 non-synonymous SNPs in the 4 glutathione peroxidase genes using the multiplex single base extension method.
19047153 2008 Glutathione Peroxidase 2 Inhibits Cyclooxygenase-2-Mediated Migration and Invasion of HT-29 Adenocarcinoma Cells but Supports Their Growth as Tumors in Nude Mice.
18676680 2008 Pathway-based evaluation of 380 candidate genes and lung cancer susceptibility suggests the importance of the cell cycle pathway.
18483336 2008 Variation in the selenoenzyme genes and risk of advanced distal colorectal adenoma.
18479189 2008 GPx2 counteracts PGE2 production by dampening COX-2 and mPGES-1 expression in human colon cancer cells.
18056462 2007 Gpx2 is an overexpressed gene in rat breast cancers induced by three different chemical carcinogens.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17937616 2007 Activation of the glutathione peroxidase 2 (GPx2) promoter by beta-catenin.
17277236 2007 A population-based association study of SNPs of GSTP1, MnSOD, GPX2 and Barrett's esophagus and esophageal adenocarcinoma.
16794261 2006 Glutathione peroxidase 2, the major cigarette smoke-inducible isoform of GPX in lungs, is regulated by Nrf2.
16446369 2006 GPX2, a direct target of p63, inhibits oxidative stress-induced apoptosis in a p53-dependent manner.
15923610 2005 The GI-GPx gene is a target for Nrf2.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
12751789 2003 Microflora trigger colitis in mice deficient in selenium-dependent glutathione peroxidase and induce Gpx2 gene expression.
12674495 2003 3'UTRs of glutathione peroxidases differentially affect selenium-dependent mRNA stability and selenocysteine incorporation efficiency.
12508121 2003 The DNA sequence and analysis of human chromosome 14.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11373322 2001 Immunohistochemical detection of human gastrointestinal glutathione peroxidase in normal tissues and cultured cells with novel mouse monoclonal antibodies.
11368344 2001 Human immunodeficiency virus type 1 Tat protein impairs selenoglutathione peroxidase expression and activity by a mechanism independent of cellular selenium uptake: consequences on cellular resistance to UV-A radiation.
10806356 2000 Structural organization of the human gastrointestinal glutathione peroxidase (GPX2) promoter and 3'-nontranscribed region: transcriptional response to exogenous redox agents.
10737800 2000 Shotgun sequencing of the human transcriptome with ORF expressed sequence tags.
10652368 2000 Molecular mechanism of decreased glutathione content in human immunodeficiency virus type 1 Tat-transgenic mice.
9501919 1998 Glutathione depletion associated with the HIV-1 TAT protein mediates the extracellular appearance of acidic fibroblast growth factor.
8889549 1996 Generation and analysis of 280,000 human expressed sequence tags.
8833155 1996 Polymorphism and chromosomal localization of the GI-form of human glutathione peroxidase (GPX2) on 14q24.1 by in situ hybridization.
8428933 1993 Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI.
8287691 1994 The human glutathione peroxidase genes GPX2, GPX3, and GPX4 map to chromosomes 14, 5, and 19, respectively.
8125298 1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.
2388849 1990 A human cDNA sequence of a novel glutathione peroxidase-related protein.