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). |
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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). |
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| 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). |
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Homology | SEPP1 is conserved in chimpanzee, dog, cow, mouse, rat and zebrafish. |
Expression profiling and genetic alterations of the selenoproteins GI-GPx and SePP in colorectal carcinogenesis. |
Al-Taie OH, Uceyler N, Eubner U, Jakob F, Mork H, Scheurlen M, Brigelius-Flohe R, Schottker K, Abel J, Thalheimer A, Katzenberger T, Illert B, Melcher R, Kohrle J. |
Nutr Cancer. 2004;48(1):6-14. |
PMID 15203372 |
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Selenoprotein P-expression, functions, and roles in mammals. |
Burk RF, Hill KE. |
Biochim Biophys Acta. 2009 Nov;1790(11):1441-7. Epub 2009 Apr 1. (REVIEW) |
PMID 19345254 |
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Alterations in gene expression profiles during prostate cancer progression: functional correlations to tumorigenicity and down-regulation of selenoprotein-P in mouse and human tumors. |
Calvo A, Xiao N, Kang J, Best CJ, Leiva I, Emmert-Buck MR, Jorcyk C, Green JE. |
Cancer Res. 2002 Sep 15;62(18):5325-35. |
PMID 12235003 |
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Interaction between single nucleotide polymorphisms in selenoprotein P and mitochondrial superoxide dismutase determines prostate cancer risk. |
Cooper ML, Adami HO, Gronberg H, Wiklund F, Green FR, Rayman MP. |
Cancer Res. 2008 Dec 15;68(24):10171-7. |
PMID 19074884 |
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Selenoprotein-P is down-regulated in prostate cancer, which results in lack of protection against oxidative damage. |
Gonzalez-Moreno O, Boque N, Redrado M, Milagro F, Campion J, Endermann T, Takahashi K, Saito Y, Catena R, Schomburg L, Calvo A. |
Prostate. 2010 Nov 17. [Epub ahead of print] |
PMID 21086459 |
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Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial. |
Hurst R, Armah CN, Dainty JR, Hart DJ, Teucher B, Goldson AJ, Broadley MR, Motley AK, Fairweather-Tait SJ. |
Am J Clin Nutr. 2010 Apr;91(4):923-31. Epub 2010 Feb 24. |
PMID 20181815 |
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Genetic polymorphisms in the human selenoprotein P gene determine the response of selenoprotein markers to selenium supplementation in a gender-specific manner (the SELGEN study). |
Meplan C, Crosley LK, Nicol F, Beckett GJ, Howie AF, Hill KE, Horgan G, Mathers JC, Arthur JR, Hesketh JE. |
FASEB J. 2007 Oct;21(12):3063-74. Epub 2007 May 29. |
PMID 17536041 |
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Genetic variants in selenoprotein genes increase risk of colorectal cancer. |
Meplan C, Hughes DJ, Pardini B, Naccarati A, Soucek P, Vodickova L, Hlavata I, Vrana D, Vodicka P, Hesketh JE. |
Carcinogenesis. 2010 Jun;31(6):1074-9. Epub 2010 Apr 8. |
PMID 20378690 |
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Relative abundance of selenoprotein P isoforms in human plasma depends on genotype, se intake, and cancer status. |
Meplan C, Nicol F, Burtle BT, Crosley LK, Arthur JR, Mathers JC, Hesketh JE. |
Antioxid Redox Signal. 2009 Nov;11(11):2631-40. |
PMID 19453253 |
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Reduced serum selenoprotein P concentrations in German prostate cancer patients. |
Meyer HA, Hollenbach B, Stephan C, Endermann T, Morgenthaler NG, Cammann H, Kohrle J, Jung K, Schomburg L. |
Cancer Epidemiol Biomarkers Prev. 2009 Sep;18(9):2386-90. Epub 2009 Aug 18. |
PMID 19690186 |
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Selenoprotein P in plasma in relation to cancer morbidity in middle-aged Swedish men. |
Persson-Moschos ME, Stavenow L, Akesson B, Lindgarde F. |
Nutr Cancer. 2000;36(1):19-26. |
PMID 10798212 |
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Variation in the selenoenzyme genes and risk of advanced distal colorectal adenoma. |
Peters U, Chatterjee N, Hayes RB, Schoen RE, Wang Y, Chanock SJ, Foster CB. |
Cancer Epidemiol Biomarkers Prev. 2008 May;17(5):1144-54. |
PMID 18483336 |
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Domain structure of bi-functional selenoprotein P. |
Saito Y, Sato N, Hirashima M, Takebe G, Nagasawa S, Takahashi K. |
Biochem J. 2004 Aug 1;381(Pt 3):841-6. |
PMID 15117283 |
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Characterization of selenoprotein P as a selenium supply protein. |
Saito Y, Takahashi K. |
Eur J Biochem. 2002 Nov;269(22):5746-51. |
PMID 12423375 |
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Selenoprotein P expression is controlled through interaction of the coactivator PGC-1alpha with FoxO1a and hepatocyte nuclear factor 4alpha transcription factors. |
Speckmann B, Walter PL, Alili L, Reinehr R, Sies H, Klotz LO, Steinbrenner H. |
Hepatology. 2008 Dec;48(6):1998-2006. |
PMID 18972406 |
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Effects of selenium status and polymorphisms in selenoprotein genes on prostate cancer risk in a prospective study of European men. |
Steinbrecher A, Meplan C, Hesketh J, Schomburg L, Endermann T, Jansen E, Akesson B, Rohrmann S, Linseisen J. |
Cancer Epidemiol Biomarkers Prev. 2010 Nov;19(11):2958-68. Epub 2010 Sep 17. |
PMID 20852007 |
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Optimization of selenoprotein P and other plasma selenium biomarkers for the assessment of the selenium nutritional requirement: a placebo-controlled, double-blind study of selenomethionine supplementation in selenium-deficient Chinese subjects. |
Xia Y, Hill KE, Li P, Xu J, Zhou D, Motley AK, Wang L, Byrne DW, Burk RF. |
Am J Clin Nutr. 2010 Sep;92(3):525-31. Epub 2010 Jun 23. |
PMID 20573787 |
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