Human GPx3 gene is transcribed to the GPx3 transcript of 1779 bp (NM_002084), consisting of exon 1 (1-304 bp), exon 2 (305-458), exon 3 (459-576), exon 4 (577-676), and exon 5 (677-1761). The coding DNA sequence (CDS) 218..898 bp, encodes for a protein of 226 aa, comprising a leading signal peptide sequence at 218..277 bp followed by the main coding sequence for GPx3. An OPAL codon (TGA) at 434-436 bp is translated to a Selenocycteine (Chambers et al. 1986; Fu et al. 2002; Fu et al. 2002).

Unknown.

Plasma glutathione peroxidase 3 is a member of glutathione peroxidase family, and is the only secretary glutathione peroxidase, accounting for the all glutatione peroxidase in extracellular compartment. Structurally, intracellular GPx3 has a leading signal peptide. GPx3, similar to other selenoproteins, contains a UGA OPAL codon at codon 73, which is coded for a selenocystein residue in the presence of selenium. IMAGE_2

GPx3 is a plasma glutathione peroxidase, being secreted to extracellular compartment after synthesized in cells. GPx3 mRNA is expressed in different tissues, lung, heart, breast, prostate, placenta,and kidney. But majority (almost 70%) of plasma GPx3 is thought kidney originated(Avissar et al. 1994; Tham et al. 1998). GPx3 is transported through circulation and binds to the basement membrane of epithelia of GI (Burk et al. 2011). GPx3 mRNA is detected in a variety of tissues, while most of them are not joining in the plasma GPx3(Chu et al. 1992; Maeda et al. 1997; Tham, Whitin et al. 1998), implicating the unknown function of GPx3 in other tissues or organs.

Glutathione peroxydase 3, as other tetrameric GPx enzymes using reduced glutatione as electron donor, catalyses the oxydation of reduced glutathione and the simultaneous reduction of a variety of hydrogen peroxide and organoperoxides. As a result, the GPx3 functions in the system to relieve oxidative stress as an antioxidant enzyme. The catalytic residues in GPx3 have been mapped to the location of U73, Q107 and W181(Ren et al. 1997). U73 codes for selenocycteine, a residue that is involved in the reduction of hydrogen peroxide in a catalytic cycle of its atom, from reduced selenolate anion (R-se) to oxidized selenic acid (R-Se-OH). Latter regenerates selenolate anion by GSH. In physiological PH, selenole forms anion, a good reducing source in the system(Ren, Huang et al. 1997). However, electron donor GSH is limited in the extracellular space, implicating a rate limiting factor in the antioxidative function of GPx3. Conserved domain analysis classifies glutathione peroxidase as thioredoxin-like-superfamily protein (Conserved domains database[gi|6006001|ref|NP_002075|]).
In recent studies, GPx3 protein expression was found in a variety of normal tissues or cells, while down-regulated in a number of cancers. Through Yeast Two-Hybrid analyses, GPx3 was found interacting with several proteins in cells. One of such proteins is a TP53 transactivated protein, PIG3, which positively regulates apoptosis and mediates UV-induced cell death. The interaction between GPx3 and PIG3 leads to apoptotic cell death. GPx3 with mutated OPAL codon retains its capabilities in promoting cell death, suggesting that GPx3 contains pro-apoptotic activity independent of its peroxidase function(Wang et al. 2012).

Glutathion peroxidase activity of GPx3 is conserved in other seven GPx selenocysteine containing proteins. Though encoded from different genes, all contain a common UGA OPAL codon, encoding a selenocysteine residue in coding region, an active site of enzyme activity(Tosatto et al. 2008). GPx3 sequence, if excluding signal peptide, has the highest homology (84%) and identities (72%) with GPx5 encompassing 200 out of 226 aa in the coding region; while 60% homology with GPx1, GPx2 ; but low, 46-47% with GPx4,6,7,and 8.
GPx3 is expressed in other species. Human GPx3 shares sequece homology (94%) and identities (89%) with mouse GPx3 over 226 aa including signal peptide sequence; 95-96% homology and 91-92% identities with rat(NP_071970.2)and dog (NP_001157926.1) of full coding region, but is of only limited homology to GPx3 in Xenopus Laevis (NP_001085319.2)and Zebra fish (NP_001131027.1).

Not known.