Biology:Selenoprotein P

From HandWiki
SelP, N terminus
Identifiers
SymbolSelP_N
PfamPF04592
Pfam clanCL0172
InterProIPR007671
SelP, C terminus
Identifiers
SymbolSelP_C
PfamPF04593
InterProIPR007672

Selenoprotein P is a protein that in humans is encoded by the SELENOP gene.[1][2]

Selenoprotein P is the only known eukaryotic selenoprotein that contains multiple selenocysteine (Sec). These residues are encoded by the UGA codon that normally signals translation termination. In humans, rats, and mice, it contains 10 Sec residues,[3] 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.[2]

It is a secreted glycoprotein,[4] often found in the plasma. Its precise function remains to be elucidated; however, it is thought to have antioxidant properties.[5] This particular protein contains two domains: the C terminal and N terminal domain. The N-terminal domain is larger than the C terminal[6]

Structure

The N-terminal region always contains one Sec residue, and this is separated from the C-terminal region (9-16 Sec residues) by a histidine-rich sequence.[4] The large number of Sec residues in the C-terminal portion of Selenoprotein P suggests that it may be involved in selenium transport or storage. However, it is also possible that this region has a redox function.[4]

N terminal domain

N-terminal domain allows conservation of whole body selenium and appears to supply selenium to the kidney.[7]

The structure of the N-terminal domain is larger and contains less Selenium. However it is thought to be heavily glycosylated.[7]

C terminal domain

The function of the C-terminal domain is known to be vital for maintaining levels of selenium in brain and testis tissue but not for the maintenance of whole-body selenium.[7]

The C-terminal domain is smaller in size but far more rich in selenium.[7]

Function

Selenoprotein P may have antioxidant properties. It can attach to epithelial cells, and may protect vascular endothelial cells against peroxynitrite toxicity.[5] The high selenium content of Selenoprotein P suggests that it may be involved in selenium intercellular transport or storage.[4] The promoter structure of bovine Selenoprotein P suggests that it may be involved in countering heavy metal intoxication, and may also have a developmental function.[8]

Animal models

Mice and dogs with knock-out variants in their SELENOP homologues (Selenop[9] and SELENOP[10] respectively) may develop cerebellar ataxia phenotypes.[11][12] SELENOP and neural precursor cell levels in mouse brains increase post-exercise. Mice engineered to lack SELENOP did not increase neural precursors.[13][14]

Protein interactions

Binds to heparin in a pH-dependent manner[6]

References

  1. ↑ "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. doi:10.1073/pnas.90.2.537. PMID 8421687. Bibcode: 1993PNAS...90..537H. 
  2. ↑ 2.0 2.1 "Entrez Gene: SELENOP selenoprotein P". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=6414. 
  3. ↑ Burk and Hill 2009
  4. ↑ 4.0 4.1 4.2 4.3 "Selenium metabolism in zebrafish: multiplicity of selenoprotein genes and expression of a protein containing 17 selenocysteine residues". Genes to Cells 5 (12): 1049–1060. December 2000. doi:10.1046/j.1365-2443.2000.00392.x. PMID 11168591. 
  5. ↑ 5.0 5.1 "Selenoprotein P: properties, functions, and regulation". Archives of Biochemistry and Biophysics 376 (2): 433–438. April 2000. doi:10.1006/abbi.2000.1735. PMID 10775431. 
  6. ↑ 6.0 6.1 "Selenoprotein P-expression, functions, and roles in mammals". Biochimica et Biophysica Acta 1790 (11): 1441–1447. November 2009. doi:10.1016/j.bbagen.2009.03.026. PMID 19345254. 
  7. ↑ 7.0 7.1 7.2 7.3 "The selenium-rich C-terminal domain of mouse selenoprotein P is necessary for the supply of selenium to brain and testis but not for the maintenance of whole body selenium". The Journal of Biological Chemistry 282 (15): 10972–10980. April 2007. doi:10.1074/jbc.M700436200. PMID 17311913. 
  8. ↑ "Analysis of bovine selenoprotein P-like protein gene and availability of metal responsive element (MRE) located in its promoter". Gene 199 (1–2): 211–217. October 1997. doi:10.1016/S0378-1119(97)00369-7. PMID 9358058. 
  9. ↑ "Selenop selenoprotein P [Mus musculus (house mouse) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/20363. 
  10. ↑ "SELENOP selenoprotein P [Canis lupus familiaris (dog) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/479346. 
  11. ↑ "Deletion of the SELENOP gene leads to CNS atrophy with cerebellar ataxia in dogs". PLoS Genetics 17 (8). August 2021. doi:10.1371/journal.pgen.1009716. PMID 34339417. 
  12. ↑ "Gene disruption discloses role of selenoprotein P in selenium delivery to target tissues". The Biochemical Journal 370 (Pt 2): 397–402. March 2003. doi:10.1042/bj20021853. PMID 12521380. 
  13. ↑ "Widely available supplement may explain brain boost from exercise". February 3, 2022. https://www.science.org/content/article/widely-available-supplement-may-explain-brain-boost-exercise. 
  14. ↑ "Selenium mediates exercise-induced adult neurogenesis and reverses learning deficits induced by hippocampal injury and aging". Cell Metabolism 34 (3): 408–423.e8. March 2022. doi:10.1016/j.cmet.2022.01.005. PMID 35120590. 
This article incorporates text from the public domain Pfam and InterPro: IPR007672

Further reading

  • "Selenoprotein P. A selenium-rich extracellular glycoprotein". The Journal of Nutrition 124 (10): 1891–1897. October 1994. doi:10.1093/jn/124.10.1891. PMID 7931697. 
  • "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. doi:10.1016/S0021-9258(18)99185-4. PMID 2037562. 
  • "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–174. January 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
  • "Purification of selenoprotein P from human plasma". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology 1204 (2): 243–249. February 1994. doi:10.1016/0167-4838(94)90014-0. PMID 8142465. 
  • "Human selenoprotein P gene maps to 5q31". Genomics 36 (3): 550–551. September 1996. doi:10.1006/geno.1996.0505. PMID 8884283. 
  • "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–156. October 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 
  • "A novel method for the purification of selenoprotein P from human plasma". Archives of Biochemistry and Biophysics 357 (2): 326–330. September 1998. doi:10.1006/abbi.1998.0809. PMID 9735174. 
  • "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. doi:10.1074/jbc.274.5.2866. PMID 9915822. 
  • "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. doi:10.1006/abio.1998.2949. PMID 9918658. 
  • "Binding of selenoprotein P to heparin: characterization with surface plasmon resonance". Biological Chemistry 381 (3): 265–268. March 2000. doi:10.1515/BC.2000.034. PMID 10782998. 
  • "Heparin-binding histidine and lysine residues of rat selenoprotein P". The Journal of Biological Chemistry 276 (19): 15823–15831. May 2001. doi:10.1074/jbc.M010405200. PMID 11278668. 
  • "Association of selenoprotein P with testosterone production in cultured Leydig cells". Archives of Andrology 47 (1): 67–76. 2001. doi:10.1080/01485010152104026. PMID 11442337. 
  • "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. doi:10.1038/sj.ejhg.5200811. PMID 12173025. 
  • "Characterization of selenoprotein P as a selenium supply protein". European Journal of Biochemistry 269 (22): 5746–5751. November 2002. doi:10.1046/j.1432-1033.2002.03298.x. PMID 12423375. 



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