GPX1

Glutathione peroxidase 1
PDB rendering based on 2f8a.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2F8A
Identifiers
Symbols	GPX1; GPXD; GSHPX1
External IDs	OMIM: 138320 MGI: 104887 HomoloGene: 20155 GeneCards: GPX1 Gene
EC number	1.11.1.9
Gene Ontology Molecular function • glutathione peroxidase activity • endopeptidase inhibitor activity • SH3 domain binding Cellular component • cytoplasm • mitochondrion • cytosol Biological process • temperature homeostasis • release of cytochrome c from mitochondria • endothelial cell development • negative regulation of inflammatory response to antigenic stimulus • purine nucleobase metabolic process • purine nucleotide catabolic process • triglyceride metabolic process • glutathione metabolic process • induction of apoptosis • sensory perception of sound • intrinsic apoptotic signaling pathway in response to oxidative stress • response to xenobiotic stimulus • response to symbiotic bacterium • response to toxic substance • UV protection • response to selenium ion • response to gamma radiation • myotube differentiation • protein oxidation • arachidonic acid metabolic process • lipoxygenase pathway • response to hydroperoxide • regulation of mammary gland epithelial cell proliferation • regulation of gene expression, epigenetic • vasodilation • response to hydrogen peroxide • hydrogen peroxide catabolic process • negative regulation of apoptotic process • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process • skeletal muscle tissue regeneration • regulation of neuron apoptotic process • blood vessel endothelial cell migration • small molecule metabolic process • fat cell differentiation • cell redox homeostasis • skeletal muscle fiber development • myoblast proliferation • interaction with symbiont • positive regulation of protein kinase B signaling cascade • nucleobase-containing small molecule metabolic process • heart contraction • angiogenesis involved in wound healing • regulation of proteasomal protein catabolic process Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2876	14775
Ensembl	ENSG00000233276	ENSMUSG00000063856
UniProt	P07203	P11352
RefSeq (mRNA)	NM_000581	NM_008160
RefSeq (protein)	NP_000572	NP_032186
Location (UCSC)	Chr 3: 49.39 – 49.4 Mb	Chr 9: 108.24 – 108.24 Mb
PubMed search	[1]	[2]

Glutathione peroxidase 1 also known as GPx-1 is an enzyme that in humans is encoded by the GPX1 gene. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Function

This gene encodes a member of the glutathione peroxidase family, consisting of eight known glutathione peroxidases (Gpx1-8) in humans. Mammalian Gpx1 (this gene), Gpx2, Gpx3, and Gpx4 have been shown to be selenium-containing enzymes, whereas Gpx6 is a selenoprotein in humans with cysteine-containing homologues in rodents. In selenoproteins, the 21st amino acid selenocysteine is inserted in the nascent polypeptide chain during the process of translational recoding of the UGA stop codon.

Glutathione peroxidase functions in the detoxification of hydrogen peroxide, and is one of the most important antioxidant enzymes in humans. It has been reported that the protein encoded by this gene protects from CD95-induced apoptosis in cultured breast cancer cells and inhibits 5-lipoxygenase in blood cells, and its overexpression delays endothelial cell growth and increases resistance to toxic challenges. This protein is one of only a few proteins known in higher vertebrates to contain selenocysteine, which occurs at the active site of glutathione peroxidase and is coded by the nonsense (stop) codon TGA.

Clinical signficance

Glutathione peroxidase 1 is characterized in a polyalanine sequence polymorphism in the N-terminal region, which includes three alleles with five, six or seven alanine (Ala) repeats in this sequence. The allele with five Ala repeats is significantly associated with breast cancer risk.

Interactions

GPX1 has been shown to interact with Abl gene.

Further reading

• Moscow JA, Morrow CS, He R, et al. (1992). "Structure and function of the 5'-flanking sequence of the human cytosolic selenium-dependent glutathione peroxidase gene (hgpx1)". J. Biol. Chem. 267 (9): 5949–58. PMID 1556108. 
• Chada S, Le Beau MM, Casey L, Newburger PE (1990). "Isolation and chromosomal localization of the human glutathione peroxidase gene". Genomics 6 (2): 268–71. doi:10.1016/0888-7543(90)90566-D. PMID 2307470. 
• Mullenbach GT, Tabrizi A, Irvine BD, et al. (1987). "Sequence of a cDNA coding for human glutathione peroxidase confirms TGA encodes active site selenocysteine". Nucleic Acids Res. 15 (13): 5484. doi:10.1093/nar/15.13.5484. PMC 305979. PMID 2955287. 
• Mullenbach GT, Tabrizi A, Irvine BD, et al. (1989). "Selenocysteine's mechanism of incorporation and evolution revealed in cDNAs of three glutathione peroxidases". Protein Eng. 2 (3): 239–46. doi:10.1093/protein/2.3.239. PMID 2976939. 
• Sukenaga Y, Ishida K, Takeda T, Takagi K (1987). "cDNA sequence coding for human glutathione peroxidase". Nucleic Acids Res. 15 (17): 7178. doi:10.1093/nar/15.17.7178. PMC 306203. PMID 3658677. 
• Ishida K, Morino T, Takagi K, Sukenaga Y (1988). "Nucleotide sequence of a human gene for glutathione peroxidase". Nucleic Acids Res. 15 (23): 10051. doi:10.1093/nar/15.23.10051. PMC 306556. PMID 3697069. 
• Moscow JA, Schmidt L, Ingram DT, et al. (1995). "Loss of heterozygosity of the human cytosolic glutathione peroxidase I gene in lung cancer". Carcinogenesis 15 (12): 2769–73. doi:10.1093/carcin/15.12.2769. PMID 8001233. 
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
• Chu FF, Doroshow JH, Esworthy RS (1993). "Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI". J. Biol. Chem. 268 (4): 2571–6. PMID 8428933. 
• Esworthy RS, Ho YS, Chu FF (1997). "The Gpx1 gene encodes mitochondrial glutathione peroxidase in the mouse liver". Arch. Biochem. Biophys. 340 (1): 59–63. doi:10.1006/abbi.1997.9901. PMID 9126277. 
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 
• Opalenik SR, Ding Q, Mallery SR, Thompson JA (1998). "Glutathione depletion associated with the HIV-1 TAT protein mediates the extracellular appearance of acidic fibroblast growth factor". Arch. Biochem. Biophys. 351 (1): 17–26. doi:10.1006/abbi.1997.0566. PMID 9501919. 
• Forsberg L, de Faire U, Morgenstern R (1999). "Low yield of polymorphisms from EST blast searching: analysis of genes related to oxidative stress and verification of the P197L polymorphism in GPX1". Hum. Mutat. 13 (4): 294–300. doi:10.1002/(SICI)1098-1004(1999)13:4<294::AID-HUMU6>3.0.CO;2-5. PMID 10220143. 
• Choi J, Liu RM, Kundu RK, et al. (2000). "Molecular mechanism of decreased glutathione content in human immunodeficiency virus type 1 Tat-transgenic mice". J. Biol. Chem. 275 (5): 3693–8. doi:10.1074/jbc.275.5.3693. PMID 10652368. 
• Legault J, Carrier C, Petrov P, et al. (2000). "Mitochondrial GPx1 decreases induced but not basal oxidative damage to mtDNA in T47D cells". Biochem. Biophys. Res. Commun. 272 (2): 416–22. doi:10.1006/bbrc.2000.2800. PMID 10833429. 
• Straif D, Werz O, Kellner R, et al. (2001). "Glutathione peroxidase-1 but not -4 is involved in the regulation of cellular 5-lipoxygenase activity in monocytic cells". Biochem. J. 349 (Pt 2): 455–61. doi:10.1042/0264-6021:3490455. PMC 1221168. PMID 10880344. 
• Richard MJ, Guiraud P, Didier C, et al. (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". Arch. Biochem. Biophys. 386 (2): 213–20. doi:10.1006/abbi.2000.2197. PMID 11368344. 
• Ishibashi N, Prokopenko O, Reuhl KR, Mirochnitchenko O (2002). "Inflammatory response and glutathione peroxidase in a model of stroke". J. Immunol. 168 (4): 1926–33. PMID 11823528. 
• Gouaze V, Andrieu-Abadie N, Cuvillier O, et al. (2003). "Glutathione peroxidase-1 protects from CD95-induced apoptosis". J. Biol. Chem. 277 (45): 42867–74. doi:10.1074/jbc.M203067200. PMID 12221075.