SELENOP (selenoprotein P, plasma, 1)

Note	SEPP1 belongs to selenoproteins, all of which contain selenium in the form of selenocysteine (SeC) and are being synthesized in the presence of UGA codon, specific stem loop structure in 3' UTR of mRNA called SECIS (Selenocysteine Insertion Sequence) and other specific factors. Selenoprotein P is a glycoprotein present mainly in plasma, where it accounts for 40 - 65% of total selenium in this blood compartment. Plasma SEPP1 concentration is regarded as a functional biomarker of human selenium status (Saito and Takahashi, 2002; Méplan et al., 2009; Xia et al., 2010).
Description	Selenoprotein P consists of 381 amino acids and contains ten selenocysteines: nine are located in Sec-rich C-terminal domain (suggested as the region responsible for selenium delivery) and one is present in N-terminal domain (region with redox properties responsible for enzymatic activity of the protein). Two protein isoforms were identified in human plasma: 50 kDa and 60 kDa (Méplan et al., 2007; Méplan et al., 2009).
Expression	SEPP1 is expressed mainly in the liver, from where it is exported to plasma and other tissues. Other organs expressing the protein include mainly brain, thyroid gland, prostate and mammary gland. Its expression has been found to be significantly reduced in cancer, including prostate, colon and lung (Gonzalez-Moreno et al., 2010). SEPP1 expression is downregulated by different cytokines (Al-Taie et al., 2002). Also hepatic factors such as insulin and glucocorticoids may regulate SEPP1 expression (Speckmann et al., 2008).
Localisation	Plasma.
Function	It is supposed that SeP is responsible for the transport of selenium within body and delivering the microelement to the cells. In brain and testis (organs, in which selenium plays an important role), SEPP1 uptake is mediated by apolipoprotein E receptor-2 (apoER2). In kidneys, the uptake is regulated by another receptor, called megalin (Burk and Hill, 2009) (figure 1). Additionally, SEPP1 is involved in the reduction of oxidative stress due to its redox properties (Saito et al., 2004).
	Figure 1. SEPP1 in selenium homeostasis and transport to the testis, brain and kidney. Whole - body selenium excretion is controlled by selenium excretion in the urine. SEPP1 and selenium excretory metabolites compete for metabolically available selenium in the liver, determining urinary selenium excretion. The lipoprotein receptor apoER2 binds SEPP1 and facilitates its uptake into the testis where selenium is incorporated into spermatozoa. ApoER2 also maintains brain selenium. SEPP1 is filtered by the kidney into the glomerular filtrate and binds to megalin in the brush border of proximal convoluted tubules. Those cells endocytose the SEPP1 bound to megalin and presumably use its selenium to synthesize plasma glutathione peroxidase (GPx3) (adapted from Burk and Hill, 2009, with the authors' permission).
Homology	SEPP1 is conserved in chimpanzee, dog, cow, mouse, rat and zebrafish.

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