In molecular biology a selenoprotein is any protein that includes a selenocysteine (Sec, U, Se-Cys) amino acid residue. Among functionally characterized selenoproteins are five glutathione peroxidases (GPX) and three thioredoxin reductases, (TrxR/TXNRD) which both contain only one Sec.[1]Selenoprotein P is the most common selenoprotein found in the plasma. It is unusual because in humans it contains 10 Sec residues, which are split into two domains, a longer N-terminal domain that contains 1 Sec, and a shorter C-terminal domain that contains 9 Sec. The longer N-terminal domain is likely an enzymatic domain, and the shorter C-terminal domain is likely a means of safely transporting the very reactive selenium atom throughout the body.[2][3]
Selenoproteins exist in all major domains of life, eukaryotes, bacteria and archaea. Among eukaryotes, selenoproteins appear to be common in animals, but rare or absent in other phyla—one has been identified in the green algaChlamydomonas, but almost none in other plants or in fungi. The American cranberry (Vaccinium macrocarpon Ait.) is the only land plant known[when?] to possess sequence-level machinery for producing selenocysteine in its mitochondrial genome, although its level of functionality is not yet determined.[4] Among bacteria and archaea, selenoproteins are only present in some lineages, while they are completely absent in many other phylogenetic groups. These observations have recently been confirmed by whole genome analysis, which shows the presence or absence of selenoprotein genes and accessory genes for the synthesis of selenoproteins in the respective organism.[citation needed]
Besides the selenocysteine-containing selenoproteins, there are also some selenoproteins known from bacterial species, which have selenium bound noncovalently. Most of these proteins are thought to contain a selenide-ligand to a molybdopterin cofactor at their active sites (e.g. nicotinate dehydrogenase of Eubacterium barkeri, or xanthine dehydrogenases). Selenium is also specifically incorporated into modified bases of some tRNAs (as 2-seleno-5-methylaminomethyl-uridine).
In addition, selenium occurs in proteins as unspecifically incorporated selenomethionine, which replaces methionine residues. Proteins containing such unspecifically incorporated selenomethionine residues are not regarded as selenoproteins. However, replacement of all methionines by selenomethionines is a widely used, recent technique in solving the phase problem during X-ray crystallographic structure determination of many proteins (MAD-phasing). While the exchange of methionines by selenomethionines appears to be tolerated (at least in bacterial cells), unspecific incorporation of selenocysteine in lieu of cysteine seems to be highly toxic. This may be one reason for the existence of a rather complicated pathway of selenocysteine biosynthesis and specific incorporation into selenoproteins, which avoids the occurrence of the free amino acid as intermediate. Thus, even if a selenocysteine-containing selenoprotein is taken up in the diet and used as selenium source, the amino acid must be degraded prior to synthesising a new selenocysteine for incorporation into a selenoprotein.
Selenium is a vital nutrient in animals, including humans. About 25 different selenocysteine-containing selenoproteins have so far been observed in human cells and tissues.[5] Since lack of selenium deprives the cell of its ability to synthesize selenoproteins, many health effects of low selenium intake are believed to be caused by the lack of one or more specific selenoproteins. Three selenoproteins, TXNRD1 (TR1), TXNRD2 (TR3) and glutathione peroxidase 4 (GPX4), have been shown to be essential in mouse knockout experiments. On the other hand, too much dietary selenium causes toxic effects and can lead to selenium poisoning. The threshold between essential and toxic concentrations of this element is rather narrow with a factor in the range of 10-100.
^Hatfield DL; Gladyshev VN (June 2002). "How selenium has altered our understanding of the genetic code". Mol. Cell. Biol. 22 (11): 3565–76. doi:10.1128/MCB.22.11.3565-3576.2002. PMC133838. PMID 11997494.
^Burk RF; Hill KE (2005). "Selenoprotein P: an extracellular protein with unique physical characteristics and a role in selenium homeostasis". Annu Rev Nutr. 25: 215–235. doi:10.1146/annurev.nutr.24.012003.132120. PMID 16011466.
^Burk RF; Hill KE (2009). "Selenoprotein P-expression, functions, and roles in mammals". Biochim Biophys Acta. 1790 (11): 1441–1447. doi:10.1016/j.bbagen.2009.03.026. PMC2763998. PMID 19345254.
^Fajardo, Diego; Schlautman, Brandon; Steffan, Shawn; Polashock, James; Vorsa, Nicholi; Zalapa, Juan (2014-02-25). "The American cranberry mitochondrial genome reveals the presence of selenocysteine (tRNA-Sec and SECIS) insertion machinery in land plants". Gene. 536 (2): 336–343. doi:10.1016/j.gene.2013.11.104. PMID 24342657.
^Avery, JA & Hoffmann, PR (2018). "Selenium, selenoproteins, and immunity". Nutrients. 10 (9): 1203. doi:10.3390/nu10091203. PMC6163284. PMID 30200430.
^G. V. Kryukov; S. Castellano; S. V. Novoselov; A. V. Lobanov; O. Zehtab; R. Guigó & V. N. Gladyshev (2003). "Characterization of mammalian selenoproteomes". Science. 300 (5624): 1439–1443. doi:10.1126/science.1083516. PMID 12775843.
^Reeves, MA & Hoffmann, PR (2009). "The human selenoproteome: recent insights into functions and regulation". Cell Mol Life Sci. 66 (15): 2457–78. doi:10.1007/s00018-009-0032-4. PMC2866081. PMID 19399585.
Further readingedit
G. V. Kryukov; S. Castellano; S. V. Novoselov; A. V. Lobanov; O. Zehtab; R. Guigó & V. N. Gladyshev (2003). "Characterization of mammalian selenoproteomes". Science. 300 (5624): 1439–1443. doi:10.1126/science.1083516. PMID 12775843.
Gregory V. Kryukov & Vadim N. Gladyshev (2004). "The prokaryotic selenoproteome". EMBO Rep. 5 (5): 538–543. doi:10.1038/sj.embor.7400126. PMC1299047. PMID 15105824.
Matilde Maiorino; Valentina Boselloa; Fulvio Ursinia; Carlo Forestab; Andrea Garollab; Margherita Scapina; Helena Sztajerc & Leopold Flohé (2003). "Genetic variations of gpx-4 and male infertility in humans". Biol Reprod. 68 (4): 1134–1141. doi:10.1095/biolreprod.102.007500. PMID 12606444.
David Fenyö & Ronald C. Beavis (2015). "Selenocysteine: Wherefore Art Thou?". J Proteome Res. 15 (2): 677–678. doi:10.1021/acs.jproteome.5b01028. PMID 26680273.
December 07, 2023
selenoprotein, molecular, biology, selenoprotein, protein, that, includes, selenocysteine, amino, acid, residue, among, functionally, characterized, selenoproteins, five, glutathione, peroxidases, three, thioredoxin, reductases, trxr, txnrd, which, both, conta. In molecular biology a selenoprotein is any protein that includes a selenocysteine Sec U Se Cys amino acid residue Among functionally characterized selenoproteins are five glutathione peroxidases GPX and three thioredoxin reductases TrxR TXNRD which both contain only one Sec 1 Selenoprotein P is the most common selenoprotein found in the plasma It is unusual because in humans it contains 10 Sec residues which are split into two domains a longer N terminal domain that contains 1 Sec and a shorter C terminal domain that contains 9 Sec The longer N terminal domain is likely an enzymatic domain and the shorter C terminal domain is likely a means of safely transporting the very reactive selenium atom throughout the body 2 3 Contents 1 Species distribution 2 Types 3 Clinical significance 4 Examples 5 See also 6 References 7 Further readingSpecies distribution editSelenoproteins exist in all major domains of life eukaryotes bacteria and archaea Among eukaryotes selenoproteins appear to be common in animals but rare or absent in other phyla one has been identified in the green alga Chlamydomonas but almost none in other plants or in fungi The American cranberry Vaccinium macrocarpon Ait is the only land plant known when to possess sequence level machinery for producing selenocysteine in its mitochondrial genome although its level of functionality is not yet determined 4 Among bacteria and archaea selenoproteins are only present in some lineages while they are completely absent in many other phylogenetic groups These observations have recently been confirmed by whole genome analysis which shows the presence or absence of selenoprotein genes and accessory genes for the synthesis of selenoproteins in the respective organism citation needed Types editThis section does not cite any sources Please help improve this section by adding citations to reliable sources Unsourced material may be challenged and removed May 2017 Learn how and when to remove this template message Besides the selenocysteine containing selenoproteins there are also some selenoproteins known from bacterial species which have selenium bound noncovalently Most of these proteins are thought to contain a selenide ligand to a molybdopterin cofactor at their active sites e g nicotinate dehydrogenase of Eubacterium barkeri or xanthine dehydrogenases Selenium is also specifically incorporated into modified bases of some tRNAs as 2 seleno 5 methylaminomethyl uridine In addition selenium occurs in proteins as unspecifically incorporated selenomethionine which replaces methionine residues Proteins containing such unspecifically incorporated selenomethionine residues are not regarded as selenoproteins However replacement of all methionines by selenomethionines is a widely used recent technique in solving the phase problem during X ray crystallographic structure determination of many proteins MAD phasing While the exchange of methionines by selenomethionines appears to be tolerated at least in bacterial cells unspecific incorporation of selenocysteine in lieu of cysteine seems to be highly toxic This may be one reason for the existence of a rather complicated pathway of selenocysteine biosynthesis and specific incorporation into selenoproteins which avoids the occurrence of the free amino acid as intermediate Thus even if a selenocysteine containing selenoprotein is taken up in the diet and used as selenium source the amino acid must be degraded prior to synthesising a new selenocysteine for incorporation into a selenoprotein Clinical significance editThis section does not cite any sources Please help improve this section by adding citations to reliable sources Unsourced material may be challenged and removed May 2017 Learn how and when to remove this template message Selenium is a vital nutrient in animals including humans About 25 different selenocysteine containing selenoproteins have so far been observed in human cells and tissues 5 Since lack of selenium deprives the cell of its ability to synthesize selenoproteins many health effects of low selenium intake are believed to be caused by the lack of one or more specific selenoproteins Three selenoproteins TXNRD1 TR1 TXNRD2 TR3 and glutathione peroxidase 4 GPX4 have been shown to be essential in mouse knockout experiments On the other hand too much dietary selenium causes toxic effects and can lead to selenium poisoning The threshold between essential and toxic concentrations of this element is rather narrow with a factor in the range of 10 100 Examples editHuman selenoproteins include Iodothyronine deiodinases 1 3 DIO1 DIO2 DIO3 Glutathione peroxidases GPX1 GPX2 GPX3 GPX4 GPX6 6 Selenoproteins SelH C11orf31 SelI EPT1 SelK SelM SelN SEPN1 SelO SelP SEPP1 SelR MSRB1 SelS SelT SelV SelW SEPW1 Sel15 7 Selenophosphate synthetase 2 SEPHS2 SPS2 Thioredoxin reductases 1 3 TXNRD1 TXNRD2 TXNRD3See also editSECIS element Mercury poisoningReferences edit Hatfield DL Gladyshev VN June 2002 How selenium has altered our understanding of the genetic code Mol Cell Biol 22 11 3565 76 doi 10 1128 MCB 22 11 3565 3576 2002 PMC 133838 PMID 11997494 Burk RF Hill KE 2005 Selenoprotein P an extracellular protein with unique physical characteristics and a role in selenium homeostasis Annu Rev Nutr 25 215 235 doi 10 1146 annurev nutr 24 012003 132120 PMID 16011466 Burk RF Hill KE 2009 Selenoprotein P expression functions and roles in mammals Biochim Biophys Acta 1790 11 1441 1447 doi 10 1016 j bbagen 2009 03 026 PMC 2763998 PMID 19345254 Fajardo Diego Schlautman Brandon Steffan Shawn Polashock James Vorsa Nicholi Zalapa Juan 2014 02 25 The American cranberry mitochondrial genome reveals the presence of selenocysteine tRNA Sec and SECIS insertion machinery in land plants Gene 536 2 336 343 doi 10 1016 j gene 2013 11 104 PMID 24342657 Avery JA amp Hoffmann PR 2018 Selenium selenoproteins and immunity Nutrients 10 9 1203 doi 10 3390 nu10091203 PMC 6163284 PMID 30200430 G V Kryukov S Castellano S V Novoselov A V Lobanov O Zehtab R Guigo amp V N Gladyshev 2003 Characterization of mammalian selenoproteomes Science 300 5624 1439 1443 doi 10 1126 science 1083516 PMID 12775843 Reeves MA amp Hoffmann PR 2009 The human selenoproteome recent insights into functions and regulation Cell Mol Life Sci 66 15 2457 78 doi 10 1007 s00018 009 0032 4 PMC 2866081 PMID 19399585 Further reading editG V Kryukov S Castellano S V Novoselov A V Lobanov O Zehtab R Guigo amp V N Gladyshev 2003 Characterization of mammalian selenoproteomes Science 300 5624 1439 1443 doi 10 1126 science 1083516 PMID 12775843 Gregory V Kryukov amp Vadim N Gladyshev 2004 The prokaryotic selenoproteome EMBO Rep 5 5 538 543 doi 10 1038 sj embor 7400126 PMC 1299047 PMID 15105824 Matilde Maiorino Valentina Boselloa Fulvio Ursinia Carlo Forestab Andrea Garollab Margherita Scapina Helena Sztajerc amp Leopold Flohe 2003 Genetic variations of gpx 4 and male infertility in humans Biol Reprod 68 4 1134 1141 doi 10 1095 biolreprod 102 007500 PMID 12606444 David Fenyo amp Ronald C Beavis 2015 Selenocysteine Wherefore Art Thou J Proteome Res 15 2 677 678 doi 10 1021 acs jproteome 5b01028 PMID 26680273 Retrieved from https en wikipedia org w index php title Selenoprotein amp oldid 1188027773, wikipedia, wiki, book, books, library,
