Summary: Selenoproteins are proteins that specifically incorporate SELENOCYSTEINE into their amino acid chain. Most selenoproteins are enzymes with the selenocysteine residues being responsible for their catalytic functions.

Top Publications

  1. Comparsi B, Meinerz D, Franco J, Posser T, Prestes A, Stefanello S, et al. Diphenyl ditelluride targets brain selenoproteins in vivo: inhibition of cerebral thioredoxin reductase and glutathione peroxidase in mice after acute exposure. Mol Cell Biochem. 2012;370:173-82 pubmed publisher
    ..In particular the inhibition of important selenoenzymes (TrxR and GPx) seems to be involved in the neurotoxicity associated with (PhTe)(2) exposure in adult mice. ..
  2. Schoenmakers E, Agostini M, Mitchell C, Schoenmakers N, Papp L, Rajanayagam O, et al. Mutations in the selenocysteine insertion sequence-binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans. J Clin Invest. 2010;120:4220-35 pubmed publisher human health, is incorporated into some proteins as selenocysteine (Sec), generating a family of selenoproteins. Sec incorporation is mediated by a multiprotein complex that includes Sec insertion sequence-binding protein ..
  3. Yim S, Chae K, Shim S, Hong J, Park J, Lee C, et al. ERK activation induced by selenium treatment significantly downregulates beta/gamma-secretase activity and Tau phosphorylation in the transgenic rat overexpressing human selenoprotein M. Int J Mol Med. 2009;24:91-6 pubmed
    ..Therefore, these results provide strong evidence that selenium treatment and SelM activate the ERK pathway to attenuate alpha/gamma-secretase-mediated proteolysis and Tau phosphorylation to protect brain function. ..
  4. Du J, Sun C, Lu B, Men L, Yao J, An L, et al. Association of SelS mRNA expression in omental adipose tissue with Homa-IR and serum amyloid A in patients with type 2 diabetes mellitus. Chin Med J (Engl). 2008;121:1165-8 pubmed
    ..SelS protein may be involved in insulin resistance in Chinese with T2DM by acting as the SAA receptor, thus playing an important role in the development of T2DM and atherosclerosis. ..
  5. Xu X, Carlson B, Irons R, Mix H, Zhong N, Gladyshev V, et al. Selenophosphate synthetase 2 is essential for selenoprotein biosynthesis. Biochem J. 2007;404:115-20 pubmed
    ..These in vivo studies indicate that SPS2 is essential for generating the selenium donor for selenocysteine biosynthesis in mammals, whereas SPS1 probably has a more specialized, non-essential role in selenoprotein metabolism. ..
  6. Shchedrina V, Everley R, Zhang Y, Gygi S, Hatfield D, Gladyshev V. Selenoprotein K binds multiprotein complexes and is involved in the regulation of endoplasmic reticulum homeostasis. J Biol Chem. 2011;286:42937-48 pubmed publisher
    ..SelK showed higher affinity for Derlin-1, whereas SelS had higher affinity for Derlin-2, suggesting that these selenoproteins could determine the nature of the substrate translocated through the Derlin channel...
  7. Fradejas N, Pastor M, Mora Lee S, Tranque P, Calvo S. SEPS1 gene is activated during astrocyte ischemia and shows prominent antiapoptotic effects. J Mol Neurosci. 2008;35:259-65 pubmed publisher
    ..Our data also support that modulation of ER stress is implicated in this effect. ..
  8. Castellano S, Gladyshev V, Guigo R, Berry M. SelenoDB 1.0 : a database of selenoprotein genes, proteins and SECIS elements. Nucleic Acids Res. 2008;36:D332-8 pubmed publisher
    b>Selenoproteins are a diverse group of proteins usually misidentified and misannotated in sequence databases...
  9. Kelly E, Greene C, Carroll T, McElvaney N, O Neill S. Selenoprotein S/SEPS1 modifies endoplasmic reticulum stress in Z variant alpha1-antitrypsin deficiency. J Biol Chem. 2009;284:16891-7 pubmed publisher
    ..This finding demonstrates a role for SEPS1 in ZAAT deficiency and suggests a possible therapeutic potential for selenium supplementation. ..

More Information


  1. Irons R, Tsuji P, Carlson B, Ouyang P, Yoo M, Xu X, et al. Deficiency in the 15-kDa selenoprotein inhibits tumorigenicity and metastasis of colon cancer cells. Cancer Prev Res (Phila). 2010;3:630-9 pubmed publisher
    Selenium has cancer-preventive activity that is mediated, in part, through selenoproteins. The role of the 15-kDa selenoprotein (Sep15) in colon cancer was assessed by preparing and using mouse colon CT26 cells stably transfected with ..
  2. Jiang L, Liu Q, Ni J. In silico identification of the sea squirt selenoproteome. BMC Genomics. 2010;11:289 pubmed publisher
    Computational methods for identifying selenoproteins have been developed rapidly in recent years...
  3. Labunskyy V, Lee B, Handy D, Loscalzo J, Hatfield D, Gladyshev V. Both maximal expression of selenoproteins and selenoprotein deficiency can promote development of type 2 diabetes-like phenotype in mice. Antioxid Redox Signal. 2011;14:2327-36 pubmed publisher
    Selenium (Se) is an essential trace element in mammals that has been shown to exert its function through selenoproteins. Whereas optimal levels of Se in the diet have important health benefits, a recent clinical trial has suggested that ..
  4. Kim K, Gao Y, Walder K, Collier G, Skelton J, Kissebah A. SEPS1 protects RAW264.7 cells from pharmacological ER stress agent-induced apoptosis. Biochem Biophys Res Commun. 2007;354:127-32 pubmed
    ..These findings suggest that SEPS1 could be a new ER stress-dependent survival factor that protects macrophage against ER stress-induced cellular dysfunction. ..
  5. Dikiy A, Novoselov S, Fomenko D, Sengupta A, Carlson B, Cerny R, et al. SelT, SelW, SelH, and Rdx12: genomics and molecular insights into the functions of selenoproteins of a novel thioredoxin-like family. Biochemistry. 2007;46:6871-82 pubmed an essential trace element in many life forms due to its occurrence as a selenocysteine (Sec) residue in selenoproteins. The majority of mammalian selenoproteins, however, have no known function...
  6. Hoffmann F, Hashimoto A, Lee B, Rose A, Shohet R, Hoffmann P. Specific antioxidant selenoproteins are induced in the heart during hypertrophy. Arch Biochem Biophys. 2011;512:38-44 pubmed publisher
  7. Zhuo P, Diamond A. Molecular mechanisms by which selenoproteins affect cancer risk and progression. Biochim Biophys Acta. 2009;1790:1546-54 pubmed publisher
    b>Selenoproteins comprise a unique class of proteins that contain selenium in the form of selenocysteine. Several selenoproteins have been implicated in the risk or development of cancers in humans by genetic data...
  8. Cheng Q, Sandalova T, Lindqvist Y, Arner E. Crystal structure and catalysis of the selenoprotein thioredoxin reductase 1. J Biol Chem. 2009;284:3998-4008 pubmed publisher
    b>Selenoproteins contain a highly reactive 21st amino acid selenocysteine (Sec) encoded by recoding of a predefined UGA codon...
  9. Penney K, Schumacher F, Li H, Kraft P, Morris J, Kurth T, et al. A large prospective study of SEP15 genetic variation, interaction with plasma selenium levels, and prostate cancer risk and survival. Cancer Prev Res (Phila). 2010;3:604-10 pubmed publisher
    ..Additionally, the association of selenium with PCa mortality was modified by a variant, suggesting the possibility that some men with PCa may benefit more from selenium than others, depending on their genotype. ..
  10. Olsson M, Olsson B, Jacobson P, Thelle D, Björkegren J, Walley A, et al. Expression of the selenoprotein S (SELS) gene in subcutaneous adipose tissue and SELS genotype are associated with metabolic risk factors. Metabolism. 2011;60:114-20 pubmed publisher
    ..This study further supports a role for SELS in the development of metabolic disease, especially in the context of insulin resistance. ..
  11. Kasaikina M, Fomenko D, Labunskyy V, Lachke S, Qiu W, Moncaster J, et al. Roles of the 15-kDa selenoprotein (Sep15) in redox homeostasis and cataract development revealed by the analysis of Sep 15 knockout mice. J Biol Chem. 2011;286:33203-12 pubmed publisher
    ..These cataracts did not appear to be associated with severe oxidative stress or glucose dysregulation. We suggest that the cataracts resulted from an improper folding status of lens proteins caused by Sep15 deficiency. ..
  12. Rengby O, Arner E. Titration and conditional knockdown of the prfB gene in Escherichia coli: effects on growth and overproduction of the recombinant mammalian selenoprotein thioredoxin reductase. Appl Environ Microbiol. 2007;73:432-41 pubmed
    ..with selenocysteine (Sec) incorporation at Sec-dedicated UGA codons, and RF2 thereby counteracts expression of selenoproteins. prfB is an essential gene in E...
  13. Sengupta A, Carlson B, Weaver J, Novoselov S, Fomenko D, Gladyshev V, et al. A functional link between housekeeping selenoproteins and phase II enzymes. Biochem J. 2008;413:151-61 pubmed publisher
    Sec (selenocysteine) is biosynthesized on its tRNA and incorporated into selenium-containing proteins (selenoproteins) as the 21st amino acid residue...
  14. Castets P, Maugenre S, Gartioux C, Rederstorff M, Krol A, Lescure A, et al. Selenoprotein N is dynamically expressed during mouse development and detected early in muscle precursors. BMC Dev Biol. 2009;9:46 pubmed publisher
    ..Interestingly, its specific expression pattern could be related to the current hypothesis that selenoprotein N may regulate the activity of the ryanodine receptors. ..
  15. Moghadaszadeh B, Beggs A. Selenoproteins and their impact on human health through diverse physiological pathways. Physiology (Bethesda). 2006;21:307-15 pubmed
    ..It is believed that the physiological effects of selenium occur mainly through the function of selenoproteins, which incorporate selenium in the form of one or more selenocysteine residues...
  16. Squires J, Berry M. Eukaryotic selenoprotein synthesis: mechanistic insight incorporating new factors and new functions for old factors. IUBMB Life. 2008;60:232-5 pubmed publisher
    ..through the incorporation of the amino acid, selenocysteine (Sec), into a unique class of proteins termed selenoproteins. Sec incorporation occurs cotranslationally at UGA codons in archaea, prokaryotes, and eukaryotes...
  17. Steinbrecher A, Méplan C, Hesketh J, Schomburg L, Endermann T, Jansen E, et al. Effects of selenium status and polymorphisms in selenoprotein genes on prostate cancer risk in a prospective study of European men. Cancer Epidemiol Biomarkers Prev. 2010;19:2958-68 pubmed publisher
    ..These findings might help to explain biological effects of selenium in prostate cancer development in order to overcome inconsistencies arising from former studies. ..
  18. Méplan C, Hughes D, Pardini B, Naccarati A, Soucek P, Vodickova L, et al. Genetic variants in selenoprotein genes increase risk of colorectal cancer. Carcinogenesis. 2010;31:1074-9 pubmed publisher
    ..Since Se exerts its biological roles through the selenoproteins, genetic variations in selenoprotein genes may influence susceptibility to CRC...
  19. Castellano S, Andres A, Bosch E, Bayés M, Guigo R, Clark A. Low exchangeability of selenocysteine, the 21st amino acid, in vertebrate proteins. Mol Biol Evol. 2009;26:2031-40 pubmed publisher
    ..b>Selenoproteins account for the dependence of vertebrates on environmental selenium (Se) and have an important role in several ..
  20. Conrad M. Transgenic mouse models for the vital selenoenzymes cytosolic thioredoxin reductase, mitochondrial thioredoxin reductase and glutathione peroxidase 4. Biochim Biophys Acta. 2009;1790:1575-85 pubmed publisher
    Selenium, as an integral part of selenoproteins, is essential for mammals...
  21. Lu C, Qiu F, Zhou H, Peng Y, Hao W, Xu J, et al. Identification and characterization of selenoprotein K: an antioxidant in cardiomyocytes. FEBS Lett. 2006;580:5189-97 pubmed
    ..Our findings indicated that SelK is a novel antioxidant in cardiomyocytes and is related to the regulation of cellular redox balance. ..
  22. Stock T, Rother M. Selenoproteins in Archaea and Gram-positive bacteria. Biochim Biophys Acta. 2009;1790:1520-32 pubmed publisher
    ..and analysis of the ever-increasing number of genome sequences has facilitated identification of the encoded selenoproteins. Available data from biochemical, sequence, and structure analyses indicate that Gram-positive bacteria ..
  23. Schara U, Kress W, BONNEMANN C, Breitbach Faller N, Korenke C, Schreiber G, et al. The phenotype and long-term follow-up in 11 patients with juvenile selenoprotein N1-related myopathy. Eur J Paediatr Neurol. 2008;12:224-30 pubmed
    ..Major complications were early respiratory failure, impaired increase in weight and orthopedic problems. There seems to be no correlation between skeletal muscle weakness and respiratory failure. ..
  24. Shrimali R, Irons R, Carlson B, Sano Y, Gladyshev V, Park J, et al. Selenoproteins mediate T cell immunity through an antioxidant mechanism. J Biol Chem. 2008;283:20181-5 pubmed publisher
    ..Selenium is incorporated into the amino acid selenocysteine (Sec), which in turn is inserted into selenoproteins in a manner dependent on Sec tRNA([Ser]Sec)...
  25. Talbot S, Nelson R, Self W. Arsenic trioxide and auranofin inhibit selenoprotein synthesis: implications for chemotherapy for acute promyelocytic leukaemia. Br J Pharmacol. 2008;154:940-8 pubmed publisher
    ..The effect of inhibitors of TrxR on selenium metabolism has yet to be assessed. This study aims to determine whether chemotherapeutics that target selenocysteine within selenoenzymes may also affect the metabolism of selenium...
  26. Zhang Y, Gladyshev V. Trends in selenium utilization in marine microbial world revealed through the analysis of the global ocean sampling (GOS) project. PLoS Genet. 2008;4:e1000095 pubmed publisher
    ..In both Pacific and Atlantic microbial communities, SelW-like and SelD were the most widespread selenoproteins. Geographic location had little influence on Sec utilization as measured by selenoprotein variety and the ..
  27. Riese C, Michaelis M, Mentrup B, Götz F, Köhrle J, Schweizer U, et al. Selenium-dependent pre- and posttranscriptional mechanisms are responsible for sexual dimorphic expression of selenoproteins in murine tissues. Endocrinology. 2006;147:5883-92 pubmed
    ..Expression of these selenoproteins is tightly controlled, and a sex-specific phenotype is observed on disturbance of selenium (Se) transport in ..
  28. Donovan J, Copeland P. Selenocysteine insertion sequence binding protein 2L is implicated as a novel post-transcriptional regulator of selenoprotein expression. PLoS ONE. 2012;7:e35581 pubmed publisher
    ..Additionally, we present the first evidence that SBP2L interacts with selenoprotein mRNAs in mammalian cells, thereby implying a role in selenoprotein expression. ..
  29. Du S, Zhou J, Jia Y, Huang K. SelK is a novel ER stress-regulated protein and protects HepG2 cells from ER stress agent-induced apoptosis. Arch Biochem Biophys. 2010;502:137-43 pubmed publisher
    ..These results suggest that SelK is an ER stress-regulated protein and plays an important role in protecting HepG2 cells from ER stress agent-induced apoptosis. ..
  30. Carlson B, Yoo M, Shrimali R, Irons R, Gladyshev V, Hatfield D, et al. Role of selenium-containing proteins in T-cell and macrophage function. Proc Nutr Soc. 2010;69:300-10 pubmed publisher
    ..These observations provided novel insights into the role of selenoproteins in the immune function and tissue homeostasis.
  31. Blauwkamp M, Yu J, Schin M, Burke K, Berry M, Carlson B, et al. Podocyte specific knock out of selenoproteins does not enhance nephropathy in streptozotocin diabetic C57BL/6 mice. BMC Nephrol. 2008;9:7 pubmed publisher
    b>Selenoproteins contain selenocysteine (Sec), commonly considered the 21st genetically encoded amino acid...
  32. Miniard A, Middleton L, Budiman M, Gerber C, Driscoll D. Nucleolin binds to a subset of selenoprotein mRNAs and regulates their expression. Nucleic Acids Res. 2010;38:4807-20 pubmed publisher
    Selenium, an essential trace element, is incorporated into selenoproteins as selenocysteine (Sec), the 21st amino acid...
  33. Carlson B, Yoo M, Sano Y, Sengupta A, Kim J, Irons R, et al. Selenoproteins regulate macrophage invasiveness and extracellular matrix-related gene expression. BMC Immunol. 2009;10:57 pubmed publisher
    ..disorders, is thought to exert its physiological effects mostly in the form of selenium-containing proteins (selenoproteins)...
  34. Rusolo F, Pucci B, Colonna G, Capone F, Guerriero E, Milone M, et al. Evaluation of selenite effects on selenoproteins and cytokinome in human hepatoma cell lines. Molecules. 2013;18:2549-62 pubmed publisher
    ..increase in proportional way with the selenite concentrations used in the treatment, suggesting that other selenoproteins can also be modulated and should be evaluated in further studies, and (iii) some cytokines, VEGF and three pro-..
  35. Arbogast S, Ferreiro A. Selenoproteins and protection against oxidative stress: selenoprotein N as a novel player at the crossroads of redox signaling and calcium homeostasis. Antioxid Redox Signal. 2010;12:893-904 pubmed publisher
    ..b>Selenoproteins are a family of proteins that contain the amino acid selenocysteine, encoded by an in-frame UGA...
  36. Jiang L, Ni J, Liu Q. Evolution of selenoproteins in the metazoan. BMC Genomics. 2012;13:446 pubmed publisher
    The selenocysteine (Sec) containing proteins, selenoproteins, are an important group of proteins present throughout all 3 kingdoms of life...
  37. Banerjee S, Yang S, Foster C. A luciferase reporter assay to investigate the differential selenium-dependent stability of selenoprotein mRNAs. J Nutr Biochem. 2012;23:1294-301 pubmed publisher
    ..To further study the Se-dependent regulation of selenoproteins, we developed a novel chemiluminescent reporter to monitor the steady-state mRNA level of an artificial ..
  38. Gao Y, Pagnon J, Feng H, Konstantopolous N, Jowett J, Walder K, et al. Secretion of the glucose-regulated selenoprotein SEPS1 from hepatoma cells. Biochem Biophys Res Commun. 2007;356:636-41 pubmed
    ..1%, average=15.7+/-1.1 ng/mL). Fractionation of human serum indicated that SEPS1 was associated with LDL and possibly with VLDL. The function of plasma SEPS1 is unclear but may be related to lipoprotein metabolism. ..
  39. Arner E. Selenoproteins-What unique properties can arise with selenocysteine in place of cysteine?. Exp Cell Res. 2010;316:1296-303 pubmed publisher
    ..With 25 human genes encoding selenoproteins and in total several thousand selenoproteins yet described in nature, it seems likely that the presence of ..
  40. Murawaki Y, Tsuchiya H, Kanbe T, Harada K, Yashima K, Nozaka K, et al. Aberrant expression of selenoproteins in the progression of colorectal cancer. Cancer Lett. 2008;259:218-30 pubmed
    ..Expression level of selenoproteins such as GPx-1, GPx-3, and SePP, which are rapidly degraded during selenium deprivation, was significantly ..
  41. Allmang C, Wurth L, Krol A. The selenium to selenoprotein pathway in eukaryotes: more molecular partners than anticipated. Biochim Biophys Acta. 2009;1790:1415-23 pubmed publisher
    ..Sec is co-translationally incorporated in selenoproteins. There are 25 selenoprotein genes in humans, and Sec was found in the active site of those that have been ..
  42. Gärtner R. Selenium and thyroid hormone axis in critical ill states: an overview of conflicting view points. J Trace Elem Med Biol. 2009;23:71-4 pubmed publisher
    ..The plasma selenium levels indicate the amount of circulating selenoproteins and selenoenzymes...
  43. Budiman M, Bubenik J, Miniard A, Middleton L, Gerber C, Cash A, et al. Eukaryotic initiation factor 4a3 is a selenium-regulated RNA-binding protein that selectively inhibits selenocysteine incorporation. Mol Cell. 2009;35:479-89 pubmed publisher
    The synthesis of selenoproteins requires the translational recoding of the UGA stop codon as selenocysteine...
  44. Lu J, Holmgren A. Selenoproteins. J Biol Chem. 2009;284:723-7 pubmed publisher
    ..The role of selenium has been attributed largely to its presence in selenoproteins as the 21st amino acid, selenocysteine (Sec, U). Sec is encoded by TGA in DNA...
  45. Suzuki T, Kelly V, Motohashi H, Nakajima O, Takahashi S, Nishimura S, et al. Deletion of the selenocysteine tRNA gene in macrophages and liver results in compensatory gene induction of cytoprotective enzymes by Nrf2. J Biol Chem. 2008;283:2021-30 pubmed
    ..Our results thus demonstrate that reduced selenoprotein activity is counterbalanced by an Nrf2-mediated cytoprotective response, which is essential for maintaining cellular redox homeostasis and viability. ..
  46. Olieric V, Wolff P, Takeuchi A, Bec G, Birck C, Vitorino M, et al. SECIS-binding protein 2, a key player in selenoprotein synthesis, is an intrinsically disordered protein. Biochimie. 2009;91:1003-9 pubmed publisher
    Selenocysteine (Sec) is co-translationally incorporated into selenoproteins at a reprogrammed UGA codon...
  47. Xu J, Arner E. Pyrroloquinoline quinone modulates the kinetic parameters of the mammalian selenoprotein thioredoxin reductase 1 and is an inhibitor of glutathione reductase. Biochem Pharmacol. 2012;83:815-20 pubmed publisher
    ..These findings may help explain several of the effects of PQQ seen in mammals. ..
  48. Rayman M. Selenoproteins and human health: insights from epidemiological data. Biochim Biophys Acta. 2009;1790:1533-40 pubmed publisher
    Knowledge of the plasma selenium levels associated with optimised concentration or activity of specific selenoproteins can provide considerable insights from epidemiological data on the possible involvement of those selenoproteins in ..
  49. Ashton K, Hooper L, Harvey L, Hurst R, Casgrain A, Fairweather Tait S. Methods of assessment of selenium status in humans: a systematic review. Am J Clin Nutr. 2009;89:2025S-2039S pubmed publisher
  50. Gromadzinska J, Reszka E, Bruzelius K, Wasowicz W, Akesson B. Selenium and cancer: biomarkers of selenium status and molecular action of selenium supplements. Eur J Nutr. 2008;47 Suppl 2:29-50 pubmed publisher
    ..To review different aspects on selenium metabolism, the occurrence of different selenoproteins and their use as biomarkers of selenium status, the results of intervention trials of the cancer-preventive ..
  51. Barnes K, Evenson J, Raines A, Sunde R. Transcript analysis of the selenoproteome indicates that dietary selenium requirements of rats based on selenium-regulated selenoprotein mRNA levels are uniformly less than those based on glutathione peroxidase activity. J Nutr. 2009;139:199-206 pubmed publisher
    ..Lastly, we did not find any selenoprotein mRNA that could be used as biomarkers for super-nutritional/anticarcinogenic levels (up to 0.8 microg Se/g diet) of Se. ..
  52. Lobanov A, Fomenko D, Zhang Y, Sengupta A, Hatfield D, Gladyshev V. Evolutionary dynamics of eukaryotic selenoproteomes: large selenoproteomes may associate with aquatic life and small with terrestrial life. Genome Biol. 2007;8:R198 pubmed publisher
    ..b>Selenoproteins occur in both eukaryotes and prokaryotes, but the selenoprotein content of organisms (selenoproteome) is ..
  53. Maiti B, Arbogast S, Allamand V, Moyle M, Anderson C, Richard P, et al. A mutation in the SEPN1 selenocysteine redefinition element (SRE) reduces selenocysteine incorporation and leads to SEPN1-related myopathy. Hum Mutat. 2009;30:411-6 pubmed publisher
    ..This data highlights the importance of the SRE element during SelN expression and illustrates a novel molecular mechanism by which point mutations may lead to SEPN1-related myopathy. ..