|Gene:||GPX3||Accession Number: G-7561 (MetaCyc)|
Synonyms: GPX-3, plasma GPX
Species: Homo sapiens
Subunit composition of
glutathione peroxidase 3 = [GPX3]4
glutathione peroxidase 3 subunit = GPX3
Glutathione peroxidases (GPxs) are a family of enzymes that scavenge peroxides generated in cells. Some isozymes have selenium-dependent glutathione peroxidase activity and contains selenocysteine encoded by a TGA codon and others do not contain selenocysteine [Arthur00a]. There are four major selenium dependent GPx isozymes in mammalian tissues; classical GPx (GPx-1; E.C. 188.8.131.52), gastrointestinal GPx (GPx-2), plasma GPx (GPx-3), and phospholipid GPx (GPx-4; E.C. 184.108.40.206). GPx-1, 2, and 3 act as homotetramers, while GPx-4 as a monomer [Arthur00a].
In addition to the selenium-containing GPXs and the proteins which contain cysteine and have similar structures to the GPXs, there are many selenium independent GPX activities in mammalian systems. These activities are mainly associated with the glutathione-S-transferases family of enzymes, whose activity is directed mainly towards organic hydroperoxides, and not hydrogen peroxide.
Gene Citations: [Takahashi90]
Molecular Weight of Polypeptide: 25.505 kD (from nucleotide sequence), 23 kD (experimental) [Broderick87 ]
Molecular Weight of Multimer: 100 kD (experimental) [Takahashi87]
Unification Links: ArrayExpress:P22352 , ModBase:P22352 , PhylomeDB:P22352 , Pride:P22352 , Protein Model Portal:P22352 , SMR:P22352 , String:9606.ENSP00000373477 , Swiss-Model:P22352 , UniProt:P22352
Relationship Links: Entrez-Nucleotide:PART-OF:D00632 , InterPro:IN-FAMILY:IPR000889 , InterPro:IN-FAMILY:IPR012336 , Panther:IN-FAMILY:PTHR11592 , PDB:Structure:2R37 , Pfam:IN-FAMILY:PF00255 , Prints:IN-FAMILY:PR01011 , Prosite:IN-FAMILY:PS00460 , Prosite:IN-FAMILY:PS00763 , Prosite:IN-FAMILY:PS51355
Enzymatic reaction of: glutathione peroxidase
EC Number: 220.127.116.11
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.
The reaction is favored in the direction shown.
GPX-3 is a glycoprotein consistent with an extracellular function. It is distinct from GPX-1. The cDNA of GPX-3 has been sequenced for many species, including human, rat, mouse and bovine. These studies predict subunit molecular weights of approximately 23-25 kDa with between 40 and 50% homology with human GPX-1 [Takahashi87]. The mRNA for GPX-3 is found predominantly in kidney, in particular the epithelial cells of the proximal tubules. A number of other cell types have been proposed to produce GPX-3 based on the presence of mRNA or immunological identification of the protein. These include heart, placenta, lung, gastrointestinal cells and thyroid. In addition, the presence of GPX-3 in milk suggests its synthesis within mammary cells.
Since GPX-3 requires millimolar concentrations of glutathione for activity, there have been questions as to whether it could function as a peroxidase in plasma (glutathione concentrations of ~0.5 mM. However, thioredoxin reductase, the thioredoxin system or glutoredoxin, can also act as electron donors for human GPX-3 at concentrations which are relevant to plasma [Bjornstedt94]. This increases the potential of the enzyme to act as an extracellular antioxidant [Arthur00a].
Bjornstedt94: Bjornstedt M, Xue J, Huang W, Akesson B, Holmgren A (1994). "The thioredoxin and glutaredoxin systems are efficient electron donors to human plasma glutathione peroxidase." J Biol Chem 269(47);29382-4. PMID: 7961915
Takahashi87: Takahashi K, Avissar N, Whitin J, Cohen H (1987). "Purification and characterization of human plasma glutathione peroxidase: a selenoglycoprotein distinct from the known cellular enzyme." Arch Biochem Biophys 256(2);677-86. PMID: 3619451
Takahashi90: Takahashi K, Akasaka M, Yamamoto Y, Kobayashi C, Mizoguchi J, Koyama J (1990). "Primary structure of human plasma glutathione peroxidase deduced from cDNA sequences." J Biochem (Tokyo) 108(2);145-8. PMID: 2229017
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