SEPP1 explained

Selenoprotein P is a protein that in humans is encoded by the SEPP1 gene.^{[1] [2]}

This gene encodes a selenoprotein containing multiple selenocysteine (Sec) residues, which are encoded by the UGA codon that normally signals translation termination. The 3' UTR of selenoprotein genes have a common stem-loop structure, the sec insertion sequence (SECIS), which is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. This selenoprotein is an extracellular glycoprotein, and is unusual in that it contains 10 Sec residues (human, rat, mouse)^[3] per polypeptide, 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.

Animal models

Mice and dogs with knock-out variants in their SEPP1 homologues (Selenop^[4] and SELENOP^[5] respectively) may develop cerebellar ataxia phenotypes.^{[6] [7]} SEPP1 and neural precursor cell levels in mouse brains increase post-exercise. Mice engineered to lack SEPP1 did not increase neural precursors.^{[8] [9]}

See also

• Selenium in biology

Further reading

• Burk RF, Hill KE . Selenoprotein P. A selenium-rich extracellular glycoprotein . The Journal of Nutrition . 124 . 10 . 1891–1897 . October 1994 . 7931697 . 10.1093/jn/124.10.1891 . free .
• Mostert V . Selenoprotein P: properties, functions, and regulation . Archives of Biochemistry and Biophysics . 376 . 2 . 433–438 . April 2000 . 10775431 . 10.1006/abbi.2000.1735 .
• Hill KE, Lloyd RS, Yang JG, Read R, Burk RF . The cDNA for rat selenoprotein P contains 10 TGA codons in the open reading frame . The Journal of Biological Chemistry . 266 . 16 . 10050–10053 . June 1991 . 2037562 . 10.1016/S0021-9258(18)99185-4 . free .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–174 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Akesson B, Bellew T, Burk RF . Purification of selenoprotein P from human plasma . Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology . 1204 . 2 . 243–249 . February 1994 . 8142465 . 10.1016/0167-4838(94)90014-0 .
• Hill KE, Dasouki M, Phillips JA, Burk RF . Human selenoprotein P gene maps to 5q31 . Genomics . 36 . 3 . 550–551 . September 1996 . 8884283 . 10.1006/geno.1996.0505 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–156 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Mostert V, Lombeck I, Abel J . A novel method for the purification of selenoprotein P from human plasma . Archives of Biochemistry and Biophysics . 357 . 2 . 326–330 . September 1998 . 9735174 . 10.1006/abbi.1998.0809 .
• Saito Y, Hayashi T, Tanaka A, Watanabe Y, Suzuki M, Saito E, Takahashi K . Selenoprotein P in human plasma as an extracellular phospholipid hydroperoxide glutathione peroxidase. Isolation and enzymatic characterization of human selenoprotein p . The Journal of Biological Chemistry . 274 . 5 . 2866–2871 . January 1999 . 9915822 . 10.1074/jbc.274.5.2866 . free .
• Koyama H, Omura K, Ejima A, Kasanuma Y, Watanabe C, Satoh H . Separation of selenium-containing proteins in human and mouse plasma using tandem high-performance liquid chromatography columns coupled with inductively coupled plasma-mass spectrometry . Analytical Biochemistry . 267 . 1 . 84–91 . February 1999 . 9918658 . 10.1006/abio.1998.2949 .
• Arteel GE, Franken S, Kappler J, Sies H . Binding of selenoprotein P to heparin: characterization with surface plasmon resonance . Biological Chemistry . 381 . 3 . 265–268 . March 2000 . 10782998 . 10.1515/BC.2000.034 . 36448244 .
• Hondal RJ, Ma S, Caprioli RM, Hill KE, Burk RF . Heparin-binding histidine and lysine residues of rat selenoprotein P . The Journal of Biological Chemistry . 276 . 19 . 15823–15831 . May 2001 . 11278668 . 10.1074/jbc.M010405200 . free .
• Nishimura K, Matsumiya K, Tsujimura A, Koga M, Kitamura M, Okuyama A . Association of selenoprotein P with testosterone production in cultured Leydig cells . Archives of Andrology . 47 . 1 . 67–76 . 2001 . 11442337 . 10.1080/01485010152104026 . 1 November 2024 .
• Al-Taie OH, Seufert J, Mörk H, Treis H, Mentrup B, Thalheimer A, Starostik P, Abel J, Scheurlen M, Köhrle J, Jakob F . A complex DNA-repeat structure within the Selenoprotein P promoter contains a functionally relevant polymorphism and is genetically unstable under conditions of mismatch repair deficiency . European Journal of Human Genetics . 10 . 9 . 499–504 . September 2002 . 12173025 . 10.1038/sj.ejhg.5200811 . free .
• Saito Y, Takahashi K . Characterization of selenoprotein P as a selenium supply protein . European Journal of Biochemistry . 269 . 22 . 5746–5751 . November 2002 . 12423375 . 10.1046/j.1432-1033.2002.03298.x . free .

Notes and References

1. Hill KE, Lloyd RS, Burk RF . Conserved nucleotide sequences in the open reading frame and 3' untranslated region of selenoprotein P mRNA . Proceedings of the National Academy of Sciences of the United States of America . 90 . 2 . 537–541 . January 1993 . 8421687 . 45698 . 10.1073/pnas.90.2.537 . free . 1993PNAS...90..537H .
2. Web site: Entrez Gene: SEPP1 selenoprotein P, plasma, 1.
3. Burk and Hill 2009
4. Web site: Selenop selenoprotein P [Mus musculus (house mouse)] - Gene - NCBI]. 2022-01-24. www.ncbi.nlm.nih.gov.
5. Web site: SELENOP selenoprotein P [Canis lupus familiaris (dog)] - Gene - NCBI]. 2022-01-24. www.ncbi.nlm.nih.gov.
6. Christen M, Högler S, Kleiter M, Leschnik M, Weber C, Thaller D, Jagannathan V, Leeb T . Deletion of the SELENOP gene leads to CNS atrophy with cerebellar ataxia in dogs . PLOS Genetics . 17 . 8 . e1009716 . August 2021 . 34339417 . 8360551 . 10.1371/journal.pgen.1009716 . free .
7. Schomburg L, Schweizer U, Holtmann B, Flohé L, Sendtner M, Köhrle J . Gene disruption discloses role of selenoprotein P in selenium delivery to target tissues . The Biochemical Journal . 370 . Pt 2 . 397–402 . March 2003 . 12521380 . 1223208 . 10.1042/bj20021853 .
8. Web site: PÉREZ ORTEGA. RODRIGO. February 3, 2022. Widely available supplement may explain brain boost from exercise. 2022-02-07. www.science.org. en.
9. Leiter. Odette. Zhuo. Zhan. Rust. Ruslan. Wasielewska. Joanna M.. Grönnert. Lisa. Kowal. Susann. Overall. Rupert W.. Adusumilli. Vijay S.. Blackmore. Daniel G.. Southon. Adam. Ganio. Katherine. 3 February 2022. Selenium mediates exercise-induced adult neurogenesis and reverses learning deficits induced by hippocampal injury and aging. Cell Metabolism. 34 . 3 . en. 408–423.e8. 10.1016/j.cmet.2022.01.005. 35120590 . 246556829 . free. 10072/418192. free.