PRDX5

Last updated

PRDX5
Protein PRDX5 PDB 1h4o.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases PRDX5 , ACR1, AOEB166, B166, HEL-S-55, PLP, PMP20, PRDX6, PRXV, prx-V, SBBI10, peroxiredoxin 5
External IDs OMIM: 606583; MGI: 1859821; HomoloGene: 8076; GeneCards: PRDX5; OMA:PRDX5 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

25824

54683

Ensembl

ENSG00000126432

ENSMUSG00000024953

UniProt

P30044

P99029

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 Mb Chr 19: 6.88 – 6.89 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

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

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

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

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

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]

Related Research Articles

Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants are frequently added to industrial products, such as polymers, fuels, and lubricants, to extend their usable lifetimes. Foods are also treated with antioxidants to forestall spoilage, in particular the rancidification of oils and fats. In cells, antioxidants such as glutathione, mycothiol, or bacillithiol, and enzyme systems like superoxide dismutase, can prevent damage from oxidative stress.

<span class="mw-page-title-main">Metallothionein</span> Family of proteins

Metallothionein (MT) is a family of cysteine-rich, low molecular weight proteins. They are localized to the membrane of the Golgi apparatus. MTs have the capacity to bind both physiological and xenobiotic heavy metals through the thiol group of its cysteine residues, which represent nearly 30% of its constituent amino acid residues.

<span class="mw-page-title-main">Reactive oxygen species</span> Highly reactive molecules formed from diatomic oxygen (O₂)

In chemistry and biology, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (O2), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (O2H), superoxide (O2-), hydroxyl radical (OH.), and singlet oxygen. ROS are pervasive because they are readily produced from O2, which is abundant. ROS are important in many ways, both beneficial and otherwise. ROS function as signals, that turn on and off biological functions. They are intermediates in the redox behavior of O2, which is central to fuel cells. ROS are central to the photodegradation of organic pollutants in the atmosphere. Most often however, ROS are discussed in a biological context, ranging from their effects on aging and their role in causing dangerous genetic mutations.

Thioredoxin reductases are enzymes that reduce thioredoxin (Trx). Two classes of thioredoxin reductase have been identified: one class in bacteria and some eukaryotes and one in animals. In bacteria TrxR also catalyzes the reduction of glutaredoxin like proteins known as NrdH. Both classes are flavoproteins which function as homodimers. Each monomer contains a FAD prosthetic group, a NADPH binding domain, and an active site containing a redox-active disulfide bond.

<span class="mw-page-title-main">Thioredoxin</span> Class of reduction–oxidation proteins

Thioredoxin is a class of small redox proteins known to be present in all organisms. It plays a role in many important biological processes, including redox signaling. In humans, thioredoxins are encoded by TXN and TXN2 genes. Loss-of-function mutation of either of the two human thioredoxin genes is lethal at the four-cell stage of the developing embryo. Although not entirely understood, thioredoxin is linked to medicine through their response to reactive oxygen species (ROS). In plants, thioredoxins regulate a spectrum of critical functions, ranging from photosynthesis to growth, flowering and the development and germination of seeds. Thioredoxins play a role in cell-to-cell communication.

<span class="mw-page-title-main">Oxidative stress</span> Free radical toxicity

Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Oxidative stress from oxidative metabolism causes base damage, as well as strand breaks in DNA. Base damage is mostly indirect and caused by the reactive oxygen species generated, e.g., O−
2, OH and H2O2. Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause disruptions in normal mechanisms of cellular signaling.

<span class="mw-page-title-main">Glutathione disulfide</span> Chemical compound

Glutathione disulfide (GSSG) is a disulfide derived from two glutathione molecules.

<span class="mw-page-title-main">Peroxiredoxin</span> Family of antioxidant enzymes

Peroxiredoxins are a ubiquitous family of antioxidant enzymes that also control cytokine-induced peroxide levels and thereby mediate signal transduction in mammalian cells. The family members in humans are PRDX1, PRDX2, PRDX3, PRDX4, PRDX5, and PRDX6. The physiological importance of peroxiredoxins is indicated by their relative abundance. Their function is the reduction of peroxides, specifically hydrogen peroxide, alkyl hydroperoxides, and peroxynitrite.

<span class="mw-page-title-main">Transcription factor Jun</span> Mammalian protein found in Homo sapiens

Transcription factor Jun is a protein that in humans is encoded by the JUN gene. c-Jun, in combination with protein c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the JUN gene. c-jun was the first oncogenic transcription factor discovered. The proto-oncogene c-Jun is the cellular homolog of the viral oncoprotein v-jun. The viral homolog v-jun was discovered in avian sarcoma virus 17 and was named for ju-nana, the Japanese word for 17. The human JUN encodes a protein that is highly similar to the viral protein, which interacts directly with specific target DNA sequences to regulate gene expression. This gene is intronless and is mapped to 1p32-p31, a chromosomal region involved in both translocations and deletions in human malignancies.

<span class="mw-page-title-main">NFE2L2</span> Human protein and coding gene

Nuclear factor erythroid 2-related factor 2 (NRF2), also known as nuclear factor erythroid-derived 2-like 2, is a transcription factor that in humans is encoded by the NFE2L2 gene. NRF2 is a basic leucine zipper (bZIP) protein that may regulate the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation, according to preliminary research. In vitro, NRF2 binds to antioxidant response elements (AREs) in the promoter regions of genes encoding cytoprotective proteins. NRF2 induces the expression of heme oxygenase 1 in vitro leading to an increase in phase II enzymes. NRF2 also inhibits the NLRP3 inflammasome.

<span class="mw-page-title-main">Glutathione peroxidase 1</span> Protein-coding gene in the species Homo sapiens

Glutathione peroxidase 1, also known as GPx1, is an enzyme that in humans is encoded by the GPX1 gene on chromosome 3. This gene encodes a member of the glutathione peroxidase family. Glutathione peroxidase functions in the detoxification of hydrogen peroxide, and is one of the most important antioxidant enzymes in humans.

<span class="mw-page-title-main">Peroxiredoxin 1</span> Protein found in humans

Peroxiredoxin-1 is a protein that in humans is encoded by the PRDX1 gene.

<span class="mw-page-title-main">Peroxiredoxin 2</span> Protein found in humans

Peroxiredoxin-2 is a protein that in humans is encoded by the PRDX2 gene.

<span class="mw-page-title-main">PRDX6</span> Protein-coding gene in the species Homo sapiens

Peroxiredoxin-6 is a protein that in humans is encoded by the PRDX6 gene. It is a member of the peroxiredoxin family of antioxidant enzymes.

<span class="mw-page-title-main">PRDX3</span> Protein-coding gene in the species Homo sapiens

Thioredoxin-dependent peroxide reductase, mitochondrial is an enzyme that in humans is encoded by the PRDX3 gene. It is a member of the peroxiredoxin family of antioxidant enzymes.

<span class="mw-page-title-main">GLRX2</span> Protein-coding gene in the species Homo sapiens

Glutaredoxin 2 (GLRX2) is an enzyme that in humans encoded by the GLRX2 gene. GLRX2, also known as GRX2, is a glutaredoxin family protein and a thiol-disulfide oxidoreductase that maintains cellular thiol homeostasis. This gene consists of four exons and three introns, spanned 10 kilobase pairs, and localized to chromosome 1q31.2–31.3.

<span class="mw-page-title-main">KLF9</span> Protein-coding gene in the species Homo sapiens

Krueppel-like factor 9 is a protein that in humans is encoded by the KLF9 gene. Previously known as Basic Transcription Element Binding Protein 1, Klf9 is part of the Sp1 C2H2-type zinc finger family of transcription factors. Several previous studies showed Klf9-related regulation of animal development, including cell differentiation of B cells, keratinocytes, and neurons. Klf9 is also a key transcriptional regulator for uterine endometrial cell proliferation, adhesion, and differentiation, all factors that are essential during the process of pregnancy and are turned off during tumorigenesis.

<span class="mw-page-title-main">PRDX4</span> Protein-coding gene in the species Homo sapiens

Peroxiredoxin-4 is a protein that in humans is encoded by the PRDX4 gene. It is a member of the peroxiredoxin family of antioxidant enzymes.

<span class="mw-page-title-main">TXN2</span> Protein-coding gene in the species Homo sapiens

Thioredoxin, mitochondrial also known as thioredoxin-2 is a protein that in humans is encoded by the TXN2 gene on chromosome 22. This nuclear gene encodes a mitochondrial member of the thioredoxin family, a group of small multifunctional redox-active proteins. The encoded protein may play important roles in the regulation of the mitochondrial membrane potential and in protection against oxidant-induced apoptosis.

Reductive stress (RS) is defined as an abnormal accumulation of reducing equivalents despite being in the presence of intact oxidation and reduction systems. A redox reaction involves the transfer of electrons from reducing agents (reductants) to oxidizing agents (oxidants) and redox couples are accountable for the majority of the cellular electron flow. RS is a state where there are more reducing equivalents compared to reductive oxygen species (ROS) in the form of known biological redox couples such as GSH/GSSG, NADP+/NADPH, and NAD+/NADH. Reductive stress is the counterpart to oxidative stress, where electron acceptors are expected to be mostly reduced. Reductive stress is likely derived from intrinsic signals that allow for the cellular defense against pro-oxidative conditions. There is a feedback regulation balance between reductive and oxidative stress where chronic RS induce oxidative species (OS), resulting in an increase in production of RS, again.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000126432 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000024953 – Ensembl, 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. 1 2 3 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. 1 2 3 4 5 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. 1 2 3 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.

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