GPX3

Glutathione peroxidase 3 (GPx-3), also known as plasma glutathione peroxidase (GPx-P) or extracellular glutathione peroxidase is an enzyme that in humans is encoded by the GPX3 gene.[5][6][7]

GPX3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2R37
Identifiers
Aliases	GPX3, GPx-P, GSHPx-3, GSHPx-P, glutathione peroxidase 3
External IDs	OMIM: 138321 MGI: 105102 HomoloGene: 20480 GeneCards: GPX3
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q33.1 Start 151,020,438 bp[1] End 151,028,992 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 B1.3 Start 54,902,453 bp[2] End 54,910,377 bp[2]
Gene ontology Molecular function • oxidoreductase activity • glutathione peroxidase activity • selenium binding • transcription factor binding • GO:0001948 protein binding • peroxidase activity Cellular component • extracellular region • extracellular exosome • extracellular Biological process • oxidation-reduction process • protein homotetramerization • response to oxidative stress • response to lipid hydroperoxide • hydrogen peroxide catabolic process • cellular oxidant detoxification • cellular response to oxidative stress Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2878	14778
Ensembl	ENSG00000211445	ENSMUSG00000018339
UniProt	P22352	P46412
RefSeq (mRNA)	NM_002084 NM_001329790	NM_001083929 NM_008161 NM_001329860
RefSeq (protein)	NP_001316719 NP_002075	NP_001316789 NP_032187
Location (UCSC)	Chr 5: 151.02 – 151.03 Mb	Chr 11: 54.9 – 54.91 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

GPx-3 belongs to the glutathione peroxidase family, which functions in the detoxification of hydrogen peroxide. It contains a selenocysteine (Sec) residue at its active site. The selenocysteine is encoded by the UGA codon, which normally signals translation termination. The 3' UTR of Sec-containing genes have a common stem-loop structure, the sec insertion sequence (SECIS), which is necessary for the recognition of UGA as a Sec codon rather than as a stop signal.[5]

Thiol specificity

GPx-3 has a wide thiol specificity. The sources of reducing power for GPx-3 in vitro include GSH, cysteine, mercaptoethanol, and dithiothreitol.[8] There is an evidence of effectiveness of homocysteine in reduction of GPx-3: GSH can be completely replaced by reduced homocysteine in vitro.[9][10]

Changes during ontogeny

In the rat blood plasma, the GPx-3 activity is low during the first two weeks after birth and rapidly increasing during transition from milk nutrition to solid food. Aging is accompanied by decrease in GPx-3 activity: in the blood plasma of rats it occurs around 23-26 months of age.[10]

References

1. GRCh38: Ensembl release 89: ENSG00000211445 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000018339 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: glutathione peroxidase 3 (plasma)".
6. Takahashi K, Avissar N, Whitin J, Cohen H (August 1987). "Purification and characterization of human plasma glutathione peroxidase: a selenoglycoprotein distinct from the known cellular enzyme". Archives of Biochemistry and Biophysics. 256 (2): 677–86. doi:10.1016/0003-9861(87)90624-2. PMID 3619451.
7. Chu FF (1994). "The human glutathione peroxidase genes GPX2, GPX3, and GPX4 map to chromosomes 14, 5, and 19, respectively". Cytogenetics and Cell Genetics. 66 (2): 96–8. doi:10.1159/000133675. PMID 8287691.
8. Takebe G, Yarimizu J, Saito Y, Hayashi T, Nakamura H, Yodoi J, et al. (October 2002). "A comparative study on the hydroperoxide and thiol specificity of the glutathione peroxidase family and selenoprotein P". The Journal of Biological Chemistry. 277 (43): 41254–8. doi:10.1074/jbc.M202773200. PMID 12185074.
9. Razygraev AV, Taborskaya KI, Petrosyan MA, Tumasova Z (May 2016). "[Thiol peroxidase activities in rat blood plasma determined with hydrogen peroxide and 5,5`-dithio-bis(2-nitrobenzoic acid)]". Biomeditsinskaia Khimiia. 62 (4): 431–8. doi:10.18097/PBMC20166204431. PMID 27562997.
10. Razygraev AV, Petrosyan MA, Tumasova ZN, Taborskaya KI, Polyanskikh LS, Baziian EV, Balashova NN (2019). "Changes in the Activity of Glutathione Peroxidase in the Blood Plasma and Serum of Rats during Postnatal Development and Aging". Advances in Gerontology. 9 (3): 283–288. doi:10.1134/s2079057019030147.

Further reading

• Guey LT, García-Closas M, Murta-Nascimento C, Lloreta J, Palencia L, Kogevinas M, et al. (February 2010). "Genetic susceptibility to distinct bladder cancer subphenotypes". European Urology. 57 (2): 283–92. doi:10.1016/j.eururo.2009.08.001. PMC 3220186. PMID 19692168.
• Lin JC, Kuo WR, Chiang FY, Hsiao PJ, Lee KW, Wu CW, Juo SH (May 2009). "Glutathione peroxidase 3 gene polymorphisms and risk of differentiated thyroid cancer". Surgery. 145 (5): 508–13. doi:10.1016/j.surg.2008.12.008. PMID 19375609.
• Holtzman JL (2002). "The role of low levels of the serum glutathione-dependent peroxidase and glutathione and high levels of serum homocysteine in the development of cardiovascular disease". Clinical Laboratory. 48 (3–4): 129–30. PMID 11934214.
• Fullerton JM, Tiwari Y, Agahi G, Heath A, Berk M, Mitchell PB, Schofield PR (August 2010). "Assessing oxidative pathway genes as risk factors for bipolar disorder". Bipolar Disorders. 12 (5): 550–6. doi:10.1111/j.1399-5618.2010.00834.x. PMID 20712757.
• Hosgood HD, Zhang L, Shen M, Berndt SI, Vermeulen R, Li G, et al. (December 2009). "Association between genetic variants in VEGF, ERCC3 and occupational benzene haematotoxicity". Occupational and Environmental Medicine. 66 (12): 848–53. doi:10.1136/oem.2008.044024. PMC 2928224. PMID 19773279.
• Liang XS, Caporaso N, McMaster ML, Ng D, Landgren O, Yeager M, et al. (August 2009). "Common genetic variants in candidate genes and risk of familial lymphoid malignancies". British Journal of Haematology. 146 (4): 418–23. doi:10.1111/j.1365-2141.2009.07790.x. PMC 2890251. PMID 19573080.
• Hosgood HD, Menashe I, He X, Chanock S, Lan Q (December 2009). "PTEN identified as important risk factor of chronic obstructive pulmonary disease". Respiratory Medicine. 103 (12): 1866–70. doi:10.1016/j.rmed.2009.06.016. PMC 2783799. PMID 19625176.
• Mistry HD, Kurlak LO, Williams PJ, Ramsay MM, Symonds ME, Broughton Pipkin F (May 2010). "Differential expression and distribution of placental glutathione peroxidases 1, 3 and 4 in normal and preeclamptic pregnancy" (PDF). Placenta. 31 (5): 401–8. doi:10.1016/j.placenta.2010.02.011. PMID 20303587.
• Hosgood HD, Menashe I, Shen M, Yeager M, Yuenger J, Rajaraman P, et al. (October 2008). "Pathway-based evaluation of 380 candidate genes and lung cancer susceptibility suggests the importance of the cell cycle pathway". Carcinogenesis. 29 (10): 1938–43. doi:10.1093/carcin/bgn178. PMC 2722857. PMID 18676680.
• Iida R, Tsubota E, Yuasa I, Takeshita H, Yasuda T (April 2009). "Simultaneous genotyping of 11 non-synonymous SNPs in the 4 glutathione peroxidase genes using the multiplex single base extension method". Clinica Chimica Acta; International Journal of Clinical Chemistry. 402 (1–2): 79–82. doi:10.1016/j.cca.2008.12.027. PMID 19161995.
• Talmud PJ, Drenos F, Shah S, Shah T, Palmen J, Verzilli C, et al. (November 2009). "Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip". American Journal of Human Genetics. 85 (5): 628–42. doi:10.1016/j.ajhg.2009.10.014. PMC 2775832. PMID 19913121.
• Wang JY, Yang IP, Wu DC, Huang SW, Wu JY, Juo SH (October 2010). "Functional glutathione peroxidase 3 polymorphisms associated with increased risk of Taiwanese patients with gastric cancer". Clinica Chimica Acta; International Journal of Clinical Chemistry. 411 (19–20): 1432–6. doi:10.1016/j.cca.2010.05.026. PMID 20576521.
• Westphal K, Stangl V, Fähling M, Dreger H, Weller A, Baumann G, et al. (December 2009). "Human-specific induction of glutathione peroxidase-3 by proteasome inhibition in cardiovascular cells". Free Radical Biology & Medicine. 47 (11): 1652–60. doi:10.1016/j.freeradbiomed.2009.09.017. PMID 19766714.
• Shen M, Vermeulen R, Rajaraman P, Menashe I, He X, Chapman RS, et al. (May 2009). "Polymorphisms in innate immunity genes and lung cancer risk in Xuanwei, China". Environmental and Molecular Mutagenesis. 50 (4): 285–90. doi:10.1002/em.20452. PMC 2666781. PMID 19170196.
• Saga Y, Ohwada M, Suzuki M, Konno R, Kigawa J, Ueno S, Mano H (December 2008). "Glutathione peroxidase 3 is a candidate mechanism of anticancer drug resistance of ovarian clear cell adenocarcinoma". Oncology Reports. 20 (6): 1299–303. doi:10.3892/or_00000144. PMID 19020706.
• Zhang X, Yang JJ, Kim YS, Kim KY, Ahn WS, Yang S (February 2010). "An 8-gene signature, including methylated and down-regulated glutathione peroxidase 3, of gastric cancer". International Journal of Oncology. 36 (2): 405–14. doi:10.3892/ijo_00000513. PMID 20043075.
• Chung SS, Kim M, Youn BS, Lee NS, Park JW, Lee IK, et al. (January 2009). "Glutathione peroxidase 3 mediates the antioxidant effect of peroxisome proliferator-activated receptor gamma in human skeletal muscle cells". Molecular and Cellular Biology. 29 (1): 20–30. doi:10.1128/MCB.00544-08. PMC 2612482. PMID 18936159.
• Wang Y, Fu W, Xie F, Wang Y, Chu X, Wang H, et al. (August 2010). "Common polymorphisms in ITGA2, PON1 and THBS2 are associated with coronary atherosclerosis in a candidate gene association study of the Chinese Han population". Journal of Human Genetics. 55 (8): 490–4. doi:10.1038/jhg.2010.53. PMID 20485444.
• Moyer AM, Sun Z, Batzler AJ, Li L, Schaid DJ, Yang P, Weinshilboum RM (March 2010). "Glutathione pathway genetic polymorphisms and lung cancer survival after platinum-based chemotherapy". Cancer Epidemiology, Biomarkers & Prevention. 19 (3): 811–21. doi:10.1158/1055-9965.EPI-09-0871. PMC 2837367. PMID 20200426.
• Bailey SD, Xie C, Do R, Montpetit A, Diaz R, Mohan V, et al. (October 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". Diabetes Care. 33 (10): 2250–3. doi:10.2337/dc10-0452. PMC 2945168. PMID 20628086.

External links

• Overview of all the structural information available in the PDB for UniProt: P22352 (Glutathione peroxidase 3) at the PDBe-KB.