Selenoprotein P is a protein that in humans is encoded by the SELENOPgene.
Selenoprotein P is the only known eukaryoticselenoprotein that contains multiple selenocysteine (Sec). These residues are encoded by the UGA codon that normally signals translation termination. In humans, rats, and mice, it contains 10 Sec residues, one located at the C-terminal side of protein and others at the N-terminal side. It is a heparin-binding protein that appears to be associated with endothelial cells, and has been implicated to function as an antioxidant in the extracellular space. Several transcript variants, encoding either the same or different isoform, have been found for this gene.
It is a secretedglycoprotein, often found in the plasma. Its precise function remains to be elucidated; however, it is thought to have antioxidant properties. This particular protein contains two domains: the C terminal and N terminal domain. The N-terminal domain is larger than the C terminal
Structure
The N-terminal region always contains one Sec residue, and this is separated from the C-terminal region (9-16 Sec residues) by a histidine-rich sequence. The large number of Sec residues in the C-terminal portion of Selenoprotein P suggests that it may be involved in selenium transport or storage. However, it is also possible that this region has a redox function.
N terminal domain
N-terminal domain allows conservation of whole body selenium and appears to supply selenium to the kidney.
The structure of the N-terminal domain is larger and contains less Selenium. However it is thought to be heavily glycosylated.
C terminal domain
The function of the C-terminal domain is known to be vital for maintaining levels of selenium in brain and testis tissue but not for the maintenance of whole-body selenium.
The C-terminal domain is smaller in size but far more rich in selenium.
Function
Selenoprotein P may have antioxidant properties. It can attach to epithelial cells, and may protect vascular endothelial cells against peroxynitritetoxicity. The high selenium content of Selenoprotein P suggests that it may be involved in selenium intercellular transport or storage. The promoterstructure of bovine Selenoprotein P suggests that it may be involved in countering heavy metal intoxication, and may also have a developmental function.
Animal models
Mice and dogs with knock-out variants in their SELENOP homologues (Selenop and SELENOP respectively) may develop cerebellar ataxia phenotypes. SELENOP and neural precursor cell levels in mouse brains increase post-exercise. Mice engineered to lack SELENOP did not increase neural precursors.
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