Why Multiples of 21? Why does Selenoprotein P Contain Multiple Selenocysteine Residues?

Abstract

Background: In animals, the 21st amino acid selenocysteine is incorporated into a restricted subset of proteins by recoding of a UGA stop codon. This recoding requires a distinctive selenocysteine insertion sequence in selenoprotein encoding mRNAs, trans-acting factors and in most cases, adequate dietary intake of selenium. With one exception, selenoproteins contain a single selenocysteine, which is incorporated with low translational efficiency. The exception is selenoprotein P, which in some species is predicted to contain as many as 132 selenocysteines and which is considered to play roles in selenium transport and storage. Objective: This study aimed to develop comparative physiological and evolutionary perspectives on the function(s) of selenoprotein P. Method: The review of the literature on the roles of selenoprotein P in diverse animals. Results: Selenoprotein P contains multiple selenocysteines, making it energetically costly to produce. Furthermore, it is often associated with detrimental effects to the animals that produce it. Possible benefits that outweigh these costs include the general storage and transport of selenium; the transport of both toxic and useful metal ions; and specific functions in reproduction and in the nervous system. Conclusion: A probable reconciliation of the negative effects of producing Selenoprotein P is its benefit in terms of promoting reproductive success.

Characterization and Quantification of Selenoprotein P: Challenges to Mass Spectrometry

“…Sci. 2021, 22, 6283 2 of 23 encoding SELENOP is distinct from that encoding other selenoproteins, in that it contains two SECIS elements instead of one [12].…”

“…2021, 22, x FOR PEER REVIEW 2 of 23 in common spider, 25 in humans [10], and 32 in oysters [11]. In vertebrates, the mRNA encoding SELENOP is distinct from that encoding other selenoproteins, in that it contains two SECIS elements instead of one [12]. Selenoprotein P is unique amongst all the characterized selenoproteins in that it contains multiple SeCys residues, whereas all other selenoproteins contain only one SeCys.…”

“…The number of SeCys residues in SELENOP from different organisms varies (Figure 1), amounting to 10 for humans, 46 in oysters [11] and 132 in one-species bivalves [13]. [11,12,14]).…”

“…Recently, the mortality risk from COVID-19 was shown to be associated with selenium deficiency, and more specifically with SELENOP deficiency, causing a dysregulation of the redox homeostasis in pathological conditions which resulted in an excessive reactive oxygen species (ROS) generation [29,30]. [11,12,14]).…”

“…Figure 1. Putative number of SeCys residues in SELENOP in different organisms (according to[11,12,14]). …”