Glutathione Peroxidase 4/GPX4: Proteins and Enzymes

Glutathione Peroxidase 4 (GPX4; also known as PHGPx) is a monomeric, 21 kDa member of the glutathione peroxidase family of proteins. It is widely expressed and serves to both protect cell membranes from phospholipid and cholesterol hydroperoxidases, and form an inactive enzyme structural component of the sperm mitochondrial capsule. Human GPX4 is 197 amino acids (aa) in length and contains a mitochondrial targeting sequence (aa 1-27) and an enzymatically active selenocysteine at Sec73. During sperm maturation, the targeting sequence is cleaved, and GPX4 may form inactive covalently-linked oligomers. There are multiple splice variants. One is ubiquitously expressed, cytoplasmic, and shows an alternate start site at Met28. A second is 226 aa in length, nuclear, and shows an Arg-rich 65 aa substitution for aa 1-28. Over amino acids 74-168, human GPX4 shares 93% aa identity with mouse GPX4.