Peroxiredoxin-5 (PRDX5), mitochondrial is a protein that in humans is encoded by the PRDX5 gene, located on chromosome 11.[5]

PRDX5
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPRDX5, ACR1, AOEB166, B166, HEL-S-55, PLP, PMP20, PRDX6, PRXV, prx-V, SBBI10, peroxiredoxin 5
External IDsOMIM: 606583; MGI: 1859821; HomoloGene: 8076; GeneCards: PRDX5; OMA:PRDX5 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_012094
NM_181651
NM_181652
NM_001358511
NM_001358516

NM_012021
NM_001358444

RefSeq (protein)

NP_036226
NP_857634
NP_857635
NP_001345440
NP_001345445

NP_036151
NP_001345373

Location (UCSC)Chr 11: 64.32 – 64.32 MbChr 19: 6.88 – 6.89 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

This gene encodes a member of the six-member peroxiredoxin family of antioxidant enzymes. Like the other five members, PRDX5 is widely expressed in tissues but differs by its large subcellular distribution.[6] In human cells, it has been shown that PRDX5 can be localized to mitochondria, peroxisomes, the cytosol, and the nucleus.[7] Human PRDX5 is identified by virtue of the sequence homologies to yeast peroxisomal antioxidant enzyme PMP20.[6][8]

Biochemically, PRDX5 is a peroxidase that can use cytosolic or mitochondrial thioredoxins to reduce alkyl hydroperoxides or peroxynitrite with high rate constants in the 106 to 107 M−1s−1 range, whereas its reaction with hydrogen peroxide is more modest, in the 105 M−1s−1 range.[7] So far, PRDX5 has been shown to be a cytoprotective antioxidant enzyme that inhibits endogenous or exogenous peroxide accumulation.[7]

Structure

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According to its amino acid sequence, this 2-Cys peroxiredoxin, PRDX5, is the most divergent isoform among mammalian peroxiredoxins, processing only 28% to 30% sequence identity with typical 2-Cys and 1-Cys peroxiredoxins.[9] The divergent amino acid sequence of this atypical peroxiredoxin is reflected in its unique crystal structure. The typical peroxiredoxin is composed of a thioredoxin domain and a C-terminal, whereas PRDX5 has an N-terminal domain and a unique alpha helix replaces a loop structure in the typical thioredoxin domain.[7] In addition, typical 2-Cys or 1-Cys peroxiredoxins are associated as anti-parallel dimers via linkage of two beta-7-strands, whereas a PRDX5 dimer is formed by close contact between an alpha-3-helix of one molecule and an alpha-5-helix from the other molecule.[7]

Function

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As a peroxiredoxin, PRDX5 has antioxidative and cytoprotective functions during oxidative stress. Overexpression of human PRDX5 has been shown to inhibit peroxide accumulation induced by TNF-alpha, PDGF, and p53 in NIH3T3 and HeLa cells and reduce cell death by exogenous peroxide in multiple organelles of CHO, HT-22, and human tendon cells.[6][10][11][12][13] Meanwhile, reduced expression of PRDX5 induces cell susceptibility to oxidative damage and etoposide, doxorubicin, MPP+, and peroxide-induced apoptosis.[14][15][16][17] In addition, expressing human PRDX5 in other organisms or tissues such as yeast, mouse brain, and Xenopus embryos also leads to protection against oxidative stress.[18][19][20] PRDX5 in Drosophila melanogaster has been shown to promote longevity in addition to antioxidant activity.[21]

Clinical significance

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By examining 98 stroke patients, Kunze et al. showed an inverse correlation between stroke progression and PRDX5 concentration, suggesting that plasma PRDX5 can be a potential biomarker of inflammation in acute stroke.[22] In human breast cancer cells, knockdown of transcription factor, GATA1, led to increased expression of PRDX5 and inhibition of apoptosis.[10] A substantial increase in PRDX5 expression has been observed in astrocytes in multiple sclerosis lesion.[23] PRDX5 has also been identified as a candidate risk gene for the inflammatory disease, sarcoidosis.[24]

Interactions

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Transcription factor GATA-binding protein 1 can bind to the PRDX5 gene and lead to increased expression of PRDX5.[10] PRDX5 has been shown to physically interact with PRDX1, PRDX2, PRDX6, SOD1, and PARK7 in at least two independent high-throughput proteomic analyses.[25]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000126432Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024953Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "PRDX5 peroxiredoxin 5 [Homo sapiens (human)]". NCBI. Retrieved 2016-07-19.
  6. ^ a b c Zhou Y, Kok KH, Chun AC, Wong CM, Wu HW, Lin MC, Fung PC, Kung H, Jin DY (February 2000). "Mouse peroxiredoxin V is a thioredoxin peroxidase that inhibits p53-induced apoptosis". Biochemical and Biophysical Research Communications. 268 (3): 921–7. doi:10.1006/bbrc.2000.2231. PMID 10679306.
  7. ^ a b c d e Knoops B, Goemaere J, Van der Eecken V, Declercq JP (August 2011). "Peroxiredoxin 5: structure, mechanism, and function of the mammalian atypical 2-Cys peroxiredoxin". Antioxidants & Redox Signaling. 15 (3): 817–29. doi:10.1089/ars.2010.3584. PMID 20977338.
  8. ^ Yamashita H, Avraham S, Jiang S, London R, Van Veldhoven PP, Subramani S, Rogers RA, Avraham H (October 1999). "Characterization of human and murine PMP20 peroxisomal proteins that exhibit antioxidant activity in vitro". The Journal of Biological Chemistry. 274 (42): 29897–904. doi:10.1074/jbc.274.42.29897. PMID 10514471.
  9. ^ Leyens G, Donnay I, Knoops B (December 2003). "Cloning of bovine peroxiredoxins-gene expression in bovine tissues and amino acid sequence comparison with rat, mouse and primate peroxiredoxins". Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology. 136 (4): 943–55. doi:10.1016/S1096-4959(03)00290-2. PMID 14662316.
  10. ^ a b c Seo MS, Kang SW, Kim K, Baines IC, Lee TH, Rhee SG (July 2000). "Identification of a new type of mammalian peroxiredoxin that forms an intramolecular disulfide as a reaction intermediate". The Journal of Biological Chemistry. 275 (27): 20346–54. doi:10.1074/jbc.M001943200. PMID 10751410.
  11. ^ Zitzler J, Link D, Schäfer R, Liebetrau W, Kazinski M, Bonin-Debs A, Behl C, Buckel P, Brinkmann U (August 2004). "High-throughput functional genomics identifies genes that ameliorate toxicity due to oxidative stress in neuronal HT-22 cells: GFPT2 protects cells against peroxide". Molecular & Cellular Proteomics. 3 (8): 834–40. doi:10.1074/mcp.M400054-MCP200. PMID 15181156.
  12. ^ Banmeyer I, Marchand C, Verhaeghe C, Vucic B, Rees JF, Knoops B (January 2004). "Overexpression of human peroxiredoxin 5 in subcellular compartments of Chinese hamster ovary cells: effects on cytotoxicity and DNA damage caused by peroxides". Free Radical Biology & Medicine. 36 (1): 65–77. doi:10.1016/j.freeradbiomed.2003.10.019. PMID 14732291.
  13. ^ Yuan J, Murrell GA, Trickett A, Landtmeters M, Knoops B, Wang MX (July 2004). "Overexpression of antioxidant enzyme peroxiredoxin 5 protects human tendon cells against apoptosis and loss of cellular function during oxidative stress". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1693 (1): 37–45. doi:10.1016/j.bbamcr.2004.04.006. PMID 15276323.
  14. ^ Avila PC, Kropotov AV, Krutilina R, Krasnodembskay A, Tomilin NV, Serikov VB (2008). "Peroxiredoxin V contributes to antioxidant defense of lung epithelial cells". Lung. 186 (2): 103–14. doi:10.1007/s00408-007-9066-2. PMID 18219526. S2CID 22699804.
  15. ^ De Simoni S, Goemaere J, Knoops B (March 2008). "Silencing of peroxiredoxin 3 and peroxiredoxin 5 reveals the role of mitochondrial peroxiredoxins in the protection of human neuroblastoma SH-SY5Y cells toward MPP+". Neuroscience Letters. 433 (3): 219–24. doi:10.1016/j.neulet.2007.12.068. PMID 18262354. S2CID 44405952.
  16. ^ Kropotov A, Gogvadze V, Shupliakov O, Tomilin N, Serikov VB, Tomilin NV, Zhivotovsky B (September 2006). "Peroxiredoxin V is essential for protection against apoptosis in human lung carcinoma cells". Experimental Cell Research. 312 (15): 2806–15. doi:10.1016/j.yexcr.2006.05.006. PMID 16781710.
  17. ^ Serikov VB, Leutenegger C, Krutilina R, Kropotov A, Pleskach N, Suh JH, Tomilin NV (January 2006). "Cigarette smoke extract inhibits expression of peroxiredoxin V and increases airway epithelial permeability". Inhalation Toxicology. 18 (1): 79–92. Bibcode:2006InhTx..18...79S. doi:10.1080/08958370500282506. PMID 16326404. S2CID 24148404.
  18. ^ Tiên Nguyên-nhu N, Knoops B (June 2003). "Mitochondrial and cytosolic expression of human peroxiredoxin 5 in Saccharomyces cerevisiae protect yeast cells from oxidative stress induced by paraquat". FEBS Letters. 544 (1–3): 148–52. Bibcode:2003FEBSL.544..148T. doi:10.1016/s0014-5793(03)00493-9. PMID 12782306. S2CID 9007934.
  19. ^ Plaisant F, Clippe A, Vander Stricht D, Knoops B, Gressens P (April 2003). "Recombinant peroxiredoxin 5 protects against excitotoxic brain lesions in newborn mice". Free Radical Biology & Medicine. 34 (7): 862–72. doi:10.1016/s0891-5849(02)01440-5. PMID 12654475.
  20. ^ Peng Y, Yang PH, Guo Y, Ng SS, Liu J, Fung PC, Tay D, Ge J, He ML, Kung HF, Lin MC (January 2004). "Catalase and peroxiredoxin 5 protect Xenopus embryos against alcohol-induced ocular anomalies". Investigative Ophthalmology & Visual Science. 45 (1): 23–9. doi:10.1167/iovs.03-0550. hdl:10722/54210. PMID 14691149.
  21. ^ Radyuk SN, Michalak K, Klichko VI, Benes J, Rebrin I, Sohal RS, Orr WC (April 2009). "Peroxiredoxin 5 confers protection against oxidative stress and apoptosis and also promotes longevity in Drosophila". The Biochemical Journal. 419 (2): 437–45. doi:10.1042/BJ20082003. PMC 2842572. PMID 19128239.
  22. ^ Kunze A, Zierath D, Tanzi P, Cain K, Becker K (February 2014). "Peroxiredoxin 5 (PRX5) is correlated inversely to systemic markers of inflammation in acute stroke". Stroke. 45 (2): 608–10. doi:10.1161/STROKEAHA.113.003813. PMC 3946812. PMID 24385276.
  23. ^ Holley JE, Newcombe J, Winyard PG, Gutowski NJ (September 2007). "Peroxiredoxin V in multiple sclerosis lesions: predominant expression by astrocytes". Multiple Sclerosis. 13 (8): 955–61. doi:10.1177/1352458507078064. PMID 17623739. S2CID 19626529.
  24. ^ Fischer A, Schmid B, Ellinghaus D, Nothnagel M, Gaede KI, Schürmann M, Lipinski S, Rosenstiel P, Zissel G, Höhne K, Petrek M, Kolek V, Pabst S, Grohé C, Grunewald J, Ronninger M, Eklund A, Padyukov L, Gieger C, Wichmann HE, Nebel A, Franke A, Müller-Quernheim J, Hofmann S, Schreiber S (November 2012). "A novel sarcoidosis risk locus for Europeans on chromosome 11q13.1". American Journal of Respiratory and Critical Care Medicine. 186 (9): 877–85. doi:10.1164/rccm.201204-0708OC. PMID 22837380.
  25. ^ Lab MT. "PRDX5 (SBBI10) Result Summary | BioGRID". thebiogrid.org. Retrieved 2016-07-19.

Further reading

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