Peroxiredoxiinit , rikkiaineenvaihdunnan asioita

PEROXIREDOXINEISTA HAKU 22.10.2017

Wikipediatekstiä on monella kielellä.

https://en.wikipedia.org/wiki/Peroxiredoxin

Peroxiredoxin

From Wikipedia, the free encyclopedia

AhpC-TSA
Structure of AhpC, a bacterial 2-cysteine peroxiredoxin from Salmonella typhimurium.
Identifiers
Symbol	AhpC-TSA
Pfam	PF00578
Pfam clan	CL0172
InterPro	IPR000866
SCOP	1prx
SUPERFAMILY	1prx
OPM superfamily	139
OPM protein	1xvw [show]Available protein structures:

peroxiredoxin
Identifiers
EC number	1.11.1.15
CAS number	207137-51-7
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO [show]Search

Peroxiredoxins (Prxs, EC 1.11.1.15; HGNC

root symbol PRDX) (pronounced per-ox-er-dox-in) are a ubiquitous family of antioxidant enzymes that also control cytokine-induced peroxide levels and thereby mediate signal transduction in mammalian cells.[1] The family members in humans are PRDX1, PRDX2, PRDX3, PRDX4, PRDX5, and PRDX6. The physiological importance of peroxiredoxins is illustrated by their relative abundance (one of the most abundant proteins in erythrocytes after hemoglobin is peroxiredoxin 2).

Contents

• 1 Classification
• 2 Catalytic cycle
• 3 Enzyme regulation
• 4 Function
• 5 Circadian clock
• 6 See also
• 7 References
  

Classification

Prxs were historically divided into three (mechanistic) classes:

• Typical 2-Cys Prxs
• Atypical 2-Cys Prxs and
• 1-Cys Prxs.

The designation of "1-Cys" and "2-Cys" Prxs was introduced in 1994[2] as it was noticed that, among the 22 Prx sequences known at the time, only one Cys residue was absolutely conserved; this is the residue now recognized as the (required) peroxidatic cysteine, C_P.

The second, semi-conserved cysteine noted at the time is the resolving cysteine, C_R, which forms an intersubunit disulfide bond with C_P in the widespread and abundant Prxs sometimes referred to as the "typical 2-Cys Prxs". Ultimately it was realized that the C_R can reside in multiple positions in various Prx family members, leading to the addition of the "atypical 2-Cys Prx" category (Prxs for which a C_R is present, but not in the "typical", originally identified position).

With the large amount of information currently available regarding Prx structures and sequences, family members are now recognized to fall into six classes or subgroups, designated as Prx1 (essentially synonymous with "typical 2-Cys"), Prx5, Prx6, PrxQ, Tpx and AhpE groups. It is now recognized that the existence and location of C_R across all 6 groups is heterogeneous. Thus, even though the "1-Cys Prx" designation was originally associated with the Prx6 group based on the lack of a C_R in human PrxVI, and many Prx6 group members appear not to have a C_R, there are "1-Cys" members in all of the subgroups. Moreover, the C_R can be located in 5 (known) locations in the structure, yielding either an intersubunit or intrasubunit disulfide bond in the oxidized protein (depending on C_R location).[3] To assist with identification of new members and the subgroup to which they belong, a searchable database (the PeroxiRedoxin classification indEX) including Prx sequences identified from GenBank (January 2008 through October 2011) was generated by bioinformatics analysis and is publicly available.[4]

Catalytic cycle

These enzymes share the same basic catalytic mechanism, in which a redox-active cysteine (the peroxidatic cysteine) in the active site is oxidized to a sulfenic acid by the peroxide substrate.[5] The recycling of the sulfenic acid back to a thiol is what distinguishes the three enzyme classes.

2-Cys peroxiredoxins are reduced by thiols such as thioredoxins, thioredoxin-like proteins, or possibly glutathione, while the 1-Cys enzymes may be reduced by ascorbic acid or glutathione in the presence of GST-π.[6] Using high resolution crystal structures, a detailed catalytic cycle has been derived for Prxs,[7] including a model for the redox-regulated oligomeric state proposed to control enzyme activity.[8]

Inactivation of these enzymes by over-oxidation (also known as hyperoxidation) of the active thiol to sulfinic acid can be reversed by sulfiredoxin.[9]

Peroxiredoxins are frequently referred to as alkyl hydroperoxide reductase (AhpC) in bacteria.[10] Other names include thiol specific antioxidant (TSA) and thioredoxin peroxidase (TPx).[11]

Mammals express six peroxiredoxins:[12]

• 1-Cys enzymes: PRDX6 (in the Prx6 group)
• 2-Cys enzymes: PRDX1, PRDX2, PRDX3, PRDX4 (all four in the Prx1 group), and PRDX5 (in the Prx5 group)
  

Enzyme regulation

Peroxiredoxins can be regulated by phosphorylation, redox status, acetylation, nitration, truncation and oligomerization states.

Function

Peroxiredoxin uses thioredoxin (Trx) to recharge after reducing hydrogen peroxide (H₂O₂) in the following reactions:[13]

• Prx(reduced) + H₂O₂ → Prx(oxidized) + 2H₂O
• Prx(oxidized) + Trx(reduced) → Prx(reduced) + Trx(oxidized)

The oxidized form of Prx is inactive, requiring the donation of electrons from reduced Trx to restore its catalytic activity.[14]

The physiological importance of peroxiredoxins is illustrated by their relative abundance (one of the most abundant proteins in erythrocytes after hemoglobin is peroxiredoxin 2) as well as studies in knockout mice. Mice lacking peroxiredoxin 1 or 2 develop severe haemolytic anemia, and are predisposed to certain haematopoietic cancers. Peroxiredoxin 1 knockout mice have a 15% reduction in lifespan.[15] Peroxiredoxin 6 knockout mice are viable and do not display obvious gross pathology, but are more sensitive to certain exogenous sources of oxidative stress, such as hyperoxia.[16] Peroxiredoxin 3 (mitochondrial matrix peroxiredoxin) knockout mice are viable and do not display obvious gross pathology. Peroxiredoxins are proposed to play a role in cell signaling by regulating H₂O₂ levels.[17]

Plant 2-Cys peroxiredoxins are post-translationally targeted to chlorop[18]lasts, where they protect the photosynthetic membrane against photooxidative damage.[19] Nuclear gene expression depends on chloroplast-to-nucleus signalling and responds to photosynthetic signals, such as the acceptor availability at photosystem II and ABA.[20]

Circadian clock

Peroxiredoxins have been implicated in the 24-hour internal circadian clock of many organisms.[21][22][23]

See also

• Catalase
• Oxidative stress
• Peroxidase
• Peroxiredoxin classification index
• Reactive oxygen species
• Superoxide dismutase
  

References

1. Rhee S, Chae H, Kim K (2005). "Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling". Free Radic Biol Med. 38 (12): 1543–52. PMID 15917183. doi:10.1016/j.freeradbiomed.2005.02.026.
2. Chae, HZ, Robison, K, Poole, LB, Church, G, Storz, G, Rhee, SG (1994). "Cloning and sequencing of thiol-specific antioxidant from mammalian brain: alkyl hydroperoxide reductase and thiol-specific antioxidant define a large family of antioxidant enzymes.". Proceedings of the National Academy of Sciences of the United States of America. 91 (15): 7017–7021. PMC 44329 . PMID 8041738. doi:10.1073/pnas.91.15.7017.
3. Perkins, Arden; Nelson, Kimberly J.; Parsonage, Derek; Poole, Leslie B.; Karplus, P. Andrew (2015-08-01). "Peroxiredoxins: guardians against oxidative stress and modulators of peroxide signaling". Trends in Biochemical Sciences. 40 (8): 435–445. ISSN 0968-0004. PMC 4509974 . PMID 26067716. doi:10.1016/j.tibs.2015.05.001.
4. Soito, Laura; Williamson, Chris; Knutson, Stacy T.; Fetrow, Jacquelyn S.; Poole, Leslie B.; Nelson, Kimberly J. (2011-01-01). "PREX: PeroxiRedoxin classification indEX, a database of subfamily assignments across the diverse peroxiredoxin family". Nucleic Acids Research. 39 (Database issue): D332–337. ISSN 1362-4962. PMC 3013668 . PMID 21036863. doi:10.1093/nar/gkq1060.
5. Claiborne A, Yeh JI, Mallett TC, Luba J, Crane EJ, Charrier V, Parsonage D (November 1999). "Protein-sulfenic acids: diverse roles for an unlikely player in enzyme catalysis and redox regulation". Biochemistry. 38 (47): 15407–16. PMID 10569923. doi:10.1021/bi992025k.
6. Monteiro G, Horta BB, Pimenta DC, Augusto O, Netto LE (March 2007). "Reduction of 1-Cys peroxiredoxins by ascorbate changes the thiol-specific antioxidant paradigm, revealing another function of vitamin C". Proc. Natl. Acad. Sci. U.S.A. 104 (12): 4886–91. PMC 1829234 . PMID 17360337. doi:10.1073/pnas.0700481104.
7. Perkins, Arden; Parsonage, Derek; Nelson, Kimberly J.; Ogba, O. Maduka; Cheong, Paul Ha-Yeon; Poole, Leslie B.; Karplus, P. Andrew (2016-10-04). "Peroxiredoxin Catalysis at Atomic Resolution". Structure (London, England: 1993). 24 (10): 1668–1678. ISSN 1878-4186. PMID 27594682. doi:10.1016/j.str.2016.07.012.
8. Wood ZA, Schröder E, Robin Harris J, Poole LB (January 2003). "Structure, mechanism and regulation of peroxiredoxins". Trends Biochem. Sci. 28 (1): 32–40. PMID 12517450. doi:10.1016/S0968-0004(02)00003-8.
9. Jönsson TJ, Lowther WT (2007). "The peroxiredoxin repair proteins". Subcell. Biochem. Subcellular Biochemistry. 44: 115–41. ISBN 978-1-4020-6050-2. PMC 2391273 . PMID 18084892. doi:10.1007/978-1-4020-6051-9_6.
10. Poole LB (January 2005). "Bacterial defenses against oxidants: mechanistic features of cysteine-based peroxidases and their flavoprotein reductases". Arch. Biochem. Biophys. 433 (1): 240–54. PMID 15581580. doi:10.1016/j.abb.2004.09.006.
11. Chae HZ, Rhee SG (May 1994). "A thiol-specific antioxidant and sequence homology to various proteins of unknown function". BioFactors. 4 (3–4): 177–80. PMID 7916964. +
    
12. Kim SY, Jo HY, Kim MH, Cha YY, Choi SW, Shim JH, Kim TJ, Lee KY (November 2008). "H2O2-dependent hyperoxidation of peroxiredoxin 6 (Prdx6) plays a role in cellular toxicity via up-regulation of iPLA2 activity". J. Biol. Chem. 283 (48): 33563–8. PMC 2662274 . PMID 18826942. doi:10.1074/jbc.M806578200.
    
13. Rhee SG, Kang SW, Chang TS, Jeong W, Kim K (July 2001). "Peroxiredoxin, a novel family of peroxidases". IUBMB Life. 52 (1–2): 35–41. PMID 11795591. doi:10.1080/15216540252774748.
14. Pillay CS, Hofmeyr JH, Olivier BG, Snoep JL, Rohwer JM (January 2009). "Enzymes or redox couples? The kinetics of thioredoxin and glutaredoxin reactions in a systems biology context". Biochem. J. 417 (1): 269–75. PMID 18694397. doi:10.1042/BJ20080690.
15. Neumann CA, Krause DS, Carman CV, Das S, Dubey DP, Abraham JL, Bronson RT, Fujiwara Y, Orkin SH, Van Etten RA (July 2003). "Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression". Nature. 424 (6948): 561–5. PMID 12891360. doi:10.1038/nature01819.
16. Muller FL, Lustgarten MS, Jang Y, Richardson A, Van Remmen H (August 2007). "Trends in oxidative aging theories". Free Radic. Biol. Med. 43 (4): 477–503. PMID 17640558. doi:10.1016/j.freeradbiomed.2007.03.034.
17. Rhee SG, Kang SW, Jeong W, Chang TS, Yang KS, Woo HA (April 2005). "Intracellular messenger function of hydrogen peroxide and its regulation by peroxiredoxins". Curr. Opin. Cell Biol. 17 (2): 183–9. PMID 15780595. doi:10.1016/j.ceb.2005.02.004.
18. Baier M, Dietz KJ (July 1997). "The plant 2-Cys peroxiredoxin BAS1 is a nuclear-encoded chloroplast protein: its expressional regulation, phylogenetic origin, and implications for its specific physiological function in plants". Plant J. 12 (1): 179–90. PMID 9263459. doi:10.1046/j.1365-313X.1997.12010179.x.
19. Baier M, Dietz KJ (April 1999). "Protective function of chloroplast 2-cysteine peroxiredoxin in photosynthesis. Evidence from transgenic Arabidopsis". Plant Physiol. 119 (4): 1407–14. PMC 32026 . PMID 10198100. doi:10.1104/pp.119.4.1407.
20. Baier M, Ströher E, Dietz KJ (August 2004). "The acceptor availability at photosystem I and ABA control nuclear expression of 2-Cys peroxiredoxin-A in Arabidopsis thaliana". Plant Cell Physiol. 45 (8): 997–1006. PMID 15356325. doi:10.1093/pcp/pch114.
21. Bass J, Takahashi JS (January 2011). "Circadian rhythms: Redox redux". Nature. 469 (7331): 476–8. PMC 3760156 . PMID 21270881. doi:10.1038/469476a. Lay summary – Science News.
22. O'Neill JS, Reddy AB (January 2011). "Circadian clocks in human red blood cells". Nature. 469 (7331): 498–503. PMC 3040566 . PMID 21270888. doi:10.1038/nature09702.
23. O'Neill JS, van Ooijen G, Dixon LE, Troein C, Corellou F, Bouget FY, Reddy AB, Millar AJ (January 2011). "Circadian rhythms persist without transcription in a eukaryote". Nature. 469 (7331): 554–8. PMC 3040569 . PMID 21270895. doi:10.1038/nature09654.
    

PRDX1, Kr.1p34.1.

https://en.wikipedia.org/wiki/Peroxiredoxin_1

Peroxiredoxin-1 is a protein that in humans is encoded by the PRDX1 gene.[5][6]

Contents

• 1 Function
• 2 Interactions
• 3 Clinical significance
• 4 References
• 5 Further reading

Function

This gene encodes a member of the peroxiredoxin family of antioxidant enzymes, which reduce hydrogen peroxide and alkyl hydroperoxides. The encoded protein may play an antioxidant protective role in cells, and may contribute to the antiviral activity of CD8(+) T-cells. This protein may have a proliferative effect and play a role in cancer development or progression. Three transcript variants encoding the same protein have been identified for this gene.[6]

Interactions

Peroxiredoxin 1 has been shown to interact with PRDX4.[7] A chemoproteomic approach has revealed that peroxiredoxin 1 is the main target of theonellasterone.[8]

Clinical significance

As enzymes that combat oxidative stress, peroxiredoxins play an important role in health and disease.[9] Peroxiredoxin 1 and peroxiredoxin 2 have been shown to be released by some cells when stimulated by LPS or TNF-alpha.[10] The released peroxiredoxin can then act to produce inflammatory cytokines.[10] The levels of peroxiredoxin 1 are elevated in pancreatic cancer and it can potentially act as a marker for the diagnosis and prognosis of this disease.[11] In some types of cancer, peroxiredoxin 1 has been determined to act as a tumor suppressor and other studies show that peroxiredoxin 1 is overexpressed in certain human cancers.[12] A recent study has found that peroxiredoxin 1 may play a role in tumorigenesis by regulating the mTOR/p70S6K pathway in esophageal squamous cell carcinoma.[12] The expression patterns of peroxiredoxin 1 along with peroxiredoxin 4 are involved in human lung cancer malignancy.[13] It has also been shown that peroxiredoxin 1 may be an important player in the pathogenesis of acute respiratory distress syndrome because of its role in promoting inflammation.[14]

PubMed tietoa: Gene PRDX1 Kr.1p34.1.

Also known as

PAG; PAGA; PAGB; PRX1; PRXI; MSP23; NKEFA; TDPX2; NKEF-A

Summary

This gene encodes a member of the peroxiredoxin family of antioxidant enzymes, which reduce hydrogen peroxide and alkyl hydroperoxides. The encoded protein may play an antioxidant protective role in cells, and may contribute to the antiviral activity of CD8(+) T-cells. This protein may have a proliferative effect and play a role in cancer development or progression. Four transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jan 2011]

Related articles in PubMed

1. Peroxiredoxin 1 (Prx1) is a dual-function enzyme by possessing Cys-independent catalase-like activity. Sun CC, et al. Biochem J, 2017 Apr 4. PMID 28219939, Free PMC Article
2. Dual role of the active-center cysteine in human peroxiredoxin 1: Peroxidase activity and heme binding. Watanabe Y, et al. Biochem Biophys Res Commun, 2017 Feb 12. PMID 28082197
3. PRX1 knockdown potentiates vitamin K3 toxicity in cancer cells: a potential new therapeutic perspective for an old drug. He T, et al. J Exp Clin Cancer Res, 2015 Dec 21. PMID 26689287, Free PMC Article
4. Overexpression of Prdx1 in hilar cholangiocarcinoma: a predictor for recurrence and prognosis. Zhou J, et al. Int J Clin Exp Pathol, 2015. PMID 26617696, Free PMC Article
5. Aberrant expression of peroxiredoxin 1 and its clinical implications in liver cancer. Sun YL, et al. World J Gastroenterol, 2015 Oct 14. PMID 26478675, Free PMC Article
   

See all (209) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

1. our findings suggest that the tumor suppressor activity of SIRT2 requires its ability to restrict the antioxidant activity of Prdx-1, thereby sensitizing breast cancer cells to reactive oxygen species -induced DNA damage and cell cytotoxicity
2. The gene signature of OPA1, CTSA, NDUFA1, STK10 and PRDX1 was able to identify patients post-implant with a sensitivity of 91% and a specificity of 86% in discrimination between post-implant group and healthy controls.
3. UV-vis spectra of heme-PRX1 suggested that Cys52 is the axial ligand of ferric heme. PRX1 peroxidase activity was lost upon heme binding, reflecting the fact that Cys52 is not only the heme-binding site but also the active center of peroxidase activity.
4. Prx1 and Prx2 are likely targets of urate hydroperoxide in cells. Oxidation of Prxs by urate hydroperoxide might affect cell function and be partially responsible for the pro-oxidant and pro-inflammatory effects of uric acid.
5. Data suggest that PRX1 is a dual-function enzyme exhibiting both thioredoxin peroxidase-like activity and catalase-like activity with varied affinities towards reactive oxygen species; studies were conducted using recombinant proteins from green spotted puffer fish Tetraodon nigroviridis and from human.
6. peroxiredoxin 1 has a role in redox sensing and transducing [review]
7. Activation of PRX1 and -2 indicate cold atmospheric plasma affects redox homeostasis in osteosarcoma cells
8. Data show that peroxiredoxins PRDX1 and PRDX2 are upregulated in tumor B cells as compared with normal counterparts.
9. Data show the protein partners of human Prx1 and Prx2 and identified three sequence motifs, or combination thereof in Prxs partners, namely: CXXC, PXXP, and LXXLL. that can be important for protein localization, function and biological pathways. [review]
10. The data indicate that Prdx1 may contribute to the development and progression of hilar cholangiocarcinoma
    

PRDX2, Kr. 19p13.13

https://en.wikipedia.org/wiki/Peroxiredoxin_2

Peroxiredoxin-2 is a protein that in humans is encoded by the PRDX2 gene.[5][6]

This gene encodes a member of the peroxiredoxin family of antioxidant enzymes, which reduce hydrogen peroxide and alkyl hydroperoxides. The encoded protein may play an antioxidant protective role in cells, and may contribute to the antiviral activity of CD8(+) T-cells. This protein may have a proliferative effect and play a role in cancer development or progression. The crystal structure of this protein has been resolved to 0.27 nm (= 2.7 angstroms). Transcript variants encoding distinct isoforms have been identified for this gene.[6]

PubMed tietoa. Gene PRDX2, Kr. 19P13.13

Also known as

PRP; TSA; PRX2; PTX1; TPX1; NKEFB; PRXII; TDPX1; NKEF-B; HEL-S-2a

Summary

This gene encodes a member of the peroxiredoxin family of antioxidant enzymes, which reduce hydrogen peroxide and alkyl hydroperoxides. The encoded protein plays an antioxidant protective role in cells, and it may contribute to the antiviral activity of CD8(+) T-cells. The crystal structure of this protein has been resolved to 2.7 angstroms. This protein prevents hemolytic anemia from oxidative stress by stabilizing hemoglobin, thus making this gene a therapeutic target for patients with hemolytic anemia. This protein may have a proliferative effect and play a role in cancer development or progression. Related pseudogenes have been identified on chromosomes 5, 6, 10 and 13. [provided by RefSeq, Mar 2013]

Related articles in PubMed

1. Expression of the Antioxidative Enzyme Peroxiredoxin 2 in Multiple Sclerosis Lesions in Relation to Inflammation. Voigt D, et al. Int J Mol Sci, 2017 Apr 4. PMID 28375164, Free PMC Article
2. Peroxiredoxin 2 is associated with colorectal cancer progression and poor survival of patients. Peng L, et al. Oncotarget, 2017 Feb 28. PMID 28125800, Free PMC Article
3. An important role for peroxiredoxin II in survival of A549 lung cancer cells resistant to gefitinib. Kwon T, et al. Exp Mol Med, 2015 May 29. PMID 26021759, Free PMC Article
4. Peroxiredoxin-2 recycling is inhibited during erythrocyte storage. Harper VM, et al. Antioxid Redox Signal, 2015 Feb 1. PMID 25264713, Free PMC Article
5. Linkage of inflammation and oxidative stress via release of glutathionylated peroxiredoxin-2, which acts as a danger signal. Salzano S, et al. Proc Natl Acad Sci U S A, 2014 Aug 19. PMID 25097261, Free PMC Article
   

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GeneRIFs: Gene References Into Functions

1. High PRDX2 expression is associated with colorectal cancer progression.
2. Knockdown of forkhead Box M1 (FoxM1) reduced Prx II levels in H-ras(G12V)-hepatocellular carcinoma (HCC) cells, indicating FoxM1 as a direct transcription factor of Prx II in HCC.
3. Prx1 and Prx2 are likely targets of urate hydroperoxide in cells. Oxidation of Prxs by urate hydroperoxide might affect cell function and be partially responsible for the pro-oxidant and pro-inflammatory effects of uric acid.
4. Data indicate that peroxiredoxin 2 (PRDX2) was upregulated in white matter multiple sclerosis (MS) lesions mainly in astrocytes, and its expression level was positively correlated with the degree of inflammation and oxidative stress, and suggest that PRDX2 expression contributes to the resistance of astrocytes against oxidative damage.
5. The levels of expression of carbonic anhydrase 2, catalase, and PRDX2 in the nipple discharge were significantly increased in breast ductal carcinoma patients as compared to controls.
6. Activation of PRX1 and -2 indicate cold atmospheric plasma affects redox homeostasis in osteosarcoma cells
7. ig-h3, Peroxiredoxin-2, and NRF2 have roles in cervical carcinogenesis
8. Data show that peroxiredoxins PRDX1 and PRDX2 are upregulated in tumor B cells as compared with normal counterparts.
9. Data show the protein partners of human Prx1 and Prx2 and identified three sequence motifs, or combination thereof in Prxs partners, namely: CXXC, PXXP, and LXXLL. that can be important for protein localization, function and biological pathways. [review]
10. Oxidative stress promotes PRX2 and PRX3 hyperoxidation and attenuates pro-survival signaling in aging chondrocytes.
    

PRDX3, Kr. 10q26.11.

PRDX3,

Thioredoxin-dependent peroxide reductase, mitochondrial is an enzyme that in humans is encoded by the PRDX3 gene.[5][6][7] It is a member of the peroxiredoxin family of antioxidant enzymes.

This gene encodes a protein with antioxidant function and is localized in the mitochondrion. This gene shows significant nucleotide sequence similarity to the gene coding for the C22 subunit of Salmonella typhimurium alkylhydroperoxide reductase. Expression of this gene product in E. coli deficient in the C22-subunit gene rescued resistance of the bacteria to alkylhydroperoxide. The human and mouse genes are highly conserved, and they map to the regions syntenic between mouse and human chromosomes. Sequence comparisons with recently cloned mammalian homologues suggest that these genes consist of a family that is responsible for regulation of cellular proliferation, differentiation, and antioxidant functions. Two transcript variants encoding two different isoforms have been found for this gene.[7]

PRDX3 has been shown to interact with MAP3K13.[8]

It has been demonstrated that serum peroxiredoxin 3 can be a valuable biomarker for the diagnosis and assessment of hepatocellular carcinoma[9] It has been shown that peroxiredoxin proteins protect MCF-7 breast cancer cells against doxorubicin-mediated toxicity.[10] Additionally, it has been shown that peroxiredoxin 3 is overexpressed in prostate cancer and promotes cancer cell survival by defending cells against the damages incurred by oxidative stress.[

PubMed tietoa Gene PRDX3 Kr. 10q26.11.

Also known as

AOP1; MER5; AOP-1; SP-22; HBC189; PRO1748; prx-III

Summary

This gene encodes a mitochondrial protein with antioxidant function. The protein is similar to the C22 subunit of Salmonella typhimurium alkylhydroperoxide reductase, and it can rescue bacterial resistance to alkylhydroperoxide in E. coli that lack the C22 subunit. The human and mouse genes are highly conserved, and they map to the regions syntenic between mouse and human chromosomes. Sequence comparisons with recently cloned mammalian homologs suggest that these genes consist of a family that is responsible for the regulation of cellular proliferation, differentiation and antioxidant functions. This family member can protect cells from oxidative stress, and it can promote cell survival in prostate cancer. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 1, 3, 13 and 22. [provided by RefSeq, Oct 2014]

Related articles in PubMed

1. Featured Article: Accelerated decline of physical strength in peroxiredoxin-3 knockout mice. Zhang YG, et al. Exp Biol Med (Maywood), 2016 Jul. PMID 27037278, Free PMC Article
2. Peroxiredoxin 3 levels regulate a mitochondrial redox setpoint in malignant mesothelioma cells. Cunniff B, et al. Redox Biol, 2014. PMID 25462069, Free PMC Article
3. Serum peroxiredoxin3 is a useful biomarker for early diagnosis and assessemnt of prognosis of hepatocellular carcinoma in Chinese patients. Shi L, et al. Asian Pac J Cancer Prev, 2014. PMID 24815434
4. Peroxiredoxin proteins protect MCF-7 breast cancer cells from doxorubicin-induced toxicity. McDonald C, et al. Int J Oncol, 2014 Jul. PMID 24789097
5. Comparative study of Hsp27, GSK3β, Wnt1 and PRDX3 in Hirschsprung's disease. Gao H, et al. Int J Exp Pathol, 2014 Jun. PMID 24773279, Free PMC Article
   

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GeneRIFs: Gene References Into Functions

1. Prx3 and Trx2 comprise an adaptive system to sense changes in atmospheric oxygen tension and influence cellular injury responses through both detoxification of mitochondrial oxidants and regulation of mitochondrial redox-dependent signaling
2. PRX3 plays a crucial role in mitochondrial homeostasis.
3. High PRX3 expression is associated with invasion of lung adenocarcinoma.
4. We also found that forkhead box protein 1 (FOXM1)-induced peroxiredoxin 3 (PRDX3) maintains the mitochondrial function, and the FOXM1/PRDX3 mitochondrial pathway maintains survival of colon CSCs
5. Oxidative stress promotes PRX2 and PRX3 hyperoxidation and attenuates pro-survival signaling in aging chondrocytes.
6. the species with one disulfide and one hyperoxidized active site was decameric for Prx2 and dimeric for Prx3. Reduction and re-oxidation of the hyperoxidized dimer of Prx3 produced hyperoxidized monomers
7. Data indicate that peroxiredoxin III (PrxIII) is a common direct target of both miroRNAs miR-26a-5p and miR-23b-3p.
8. Colon cancer stem cells overexpress the mitochondrial gene PRX3, which is required for maintenance of mitochondrial function and tumorigenesis, and is regulated by forkhead box protein 1, which also regulates expression of CD133 in these cells.
9. High serum PRDX3 levels are associated with hepatocellular carcinoma.
10. Peroxiredoxin 3 levels regulate a mitochondrial redox setpoint in malignant mesothelioma cells.
    

PRDX4, Kr. Xp22.11

1) PRDX4

1) Peroxiredoxin-4 is a protein that in humans is encoded by the PRDX4 gene.[5][6] It is a member of the peroxiredoxin family of antioxidant enzymes.

The protein encoded by this gene is an antioxidant enzyme of the peroxiredoxin family. The protein is localized to the cytoplasm. Peroxidases of the peroxiredoxin family reduce hydrogen peroxide and alkyl hydroperoxides to water and alcohol with the use of reducing equivalents derived from thiol-containing donor molecules. This protein has been found to play a regulatory role in the activation of the transcription factor NF-kappaB.[6]

PRDX4 has been shown to interact with Peroxiredoxin 1.[5]

PubMed titetoa Gene PRDX4, Kr Xp22.11.

2) https://www.ncbi.nlm.nih.gov/gene/10549

Also known as

PRX-4; AOE372; AOE37-2; HEL-S-97n

Summary

The protein encoded by this gene is an antioxidant enzyme and belongs to the peroxiredoxin family. The protein is localized to the cytoplasm. Peroxidases of the peroxiredoxin family reduce hydrogen peroxide and alkyl hydroperoxides to water and alcohol with the use of reducing equivalents derived from thiol-containing donor molecules. This protein has been found to play a regulatory role in the activation of the transcription factor NF-kappaB. [provided by RefSeq, Jul 2008]

Related articles in PubMed

1. Increased peroxiredoxin 4 levels in patients with prediabetes compared to normal glucose tolerance subjects. Gateva A, et al. Clin Endocrinol (Oxf), 2016 Oct. PMID 27303935
2. Peroxiredoxin 4 as an independent prognostic marker for survival in patients with early-stage lung squamous cell carcinoma. Hwang JA, et al. Int J Clin Exp Pathol, 2015. PMID 26261544, Free PMC Article
3. A novel reaction of peroxiredoxin 4 towards substrates in oxidative protein folding. Zhu L, et al. PLoS One, 2014. PMID 25137134, Free PMC Article
4. Peroxiredoxin 4 improves insulin biosynthesis and glucose-induced insulin secretion in insulin-secreting INS-1E cells. Mehmeti I, et al. J Biol Chem, 2014 Sep 26. PMID 25122762, Free PMC Article
5. Circulating peroxiredoxin 4 and type 2 diabetes risk: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study. Abbasi A, et al. Diabetologia, 2014 Sep. PMID 24893865, Free PMC Article
   

See all (81) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

1. levels of peroxiredoxin 4 are higher in patients with prediabetes, but are similar in subjects with and without insulin resistance, which suggests that the main factor for its increased levels is hyperglycaemia and not insulin sensitivity state.
2. Results show that ERp44 binds the oxidized but not the reduced form of Prx4; the ERp44-Prx4 complex is formed via thiol-disulfide interchange reactions, and its crystal structure reveals a redox-dependent recognition.
3. Prdx4 expression was closely related to follicular development and has aprominent role in protecting human and mouse granulosa cells from reactive oxygen species damage.
4. Positive Prx 4 expression is significantly correlated with recurrence and shorter disease-free survival in patients with early-stage lung squamous cell carcinoma.
5. An off-pathway reaction in the Prx4-mediated oxidative protein folding.
6. Findings suggest that elevated serum Prx4 levels are associated with a higher risk of incident type 2 diabetes
7. Prx4 is a circulating antioxidant and is independently associated with increased risk of cardiovascular and all-cause mortality in T2DM.
8. these data suggest an important role of Prdx4 in maintaining insulin levels and improving the ER folding capacity also under conditions of a high insulin requirement.
9. there is a significant difference in concentration of Prx4 between cardiac arrest patients with good and poor outcome
10. The structure and function of PRDX4 as well as its sensitivity to hyperoxidation. [Review]
    

PRDX5, Kr11q.13.1

https://en.wikipedia.org/wiki/PRDX5

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] Interestingly, 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.[2

PubMed Gene PRDX5, Kr11q.13.1

Also known as

PLP; ACR1; B166; PRXV; PMP20; PRDX6; prx-V; SBBI10; AOEB166; HEL-S-55

Summary

This gene encodes a member of the peroxiredoxin family of antioxidant enzymes, which reduce hydrogen peroxide and alkyl hydroperoxides. The encoded protein may play an antioxidant protective role in different tissues under normal conditions and during inflammatory processes. This protein interacts with peroxisome receptor 1. The crystal structure of this protein in its reduced form has been resolved to 1.5 angstrom resolution. This gene uses alternate in-frame translation initiation sites to generate mitochondrial or peroxisomal/cytoplasmic forms. Three transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

Related articles in PubMed

1. Peroxiredoxin 5 promotes the epithelial-mesenchymal transition in colon cancer. Ahn HM, et al. Biochem Biophys Res Commun, 2017 Jun 3. PMID 28431931
2. Antioxidant cytoprotection by peroxisomal peroxiredoxin-5. Walbrecq G, et al. Free Radic Biol Med, 2015 Jul. PMID 25772011
3. Comparing binding modes of analogous fragments using NMR in fragment-based drug design: application to PRDX5. Aguirre C, et al. PLoS One, 2014. PMID 25025339, Free PMC Article
4. Peroxiredoxin 5 (PRX5) is correlated inversely to systemic markers of inflammation in acute stroke. Kunze A, et al. Stroke, 2014 Feb. PMID 24385276, Free PMC Article
5. Mitochondrial peroxiredoxin-5 as potential modulator of mitochondria-ER crosstalk in MPP+-induced cell death. De Simoni S, et al. J Neurochem, 2013 May. PMID 23216451
   

See all (70) citations in PubMed

GeneRIFs: Gene References Into Functions

1. The PRX5 can be used as a predictive biomarker and serves as a putative therapeutic target for the development of clinical treatments for human CRC.
2. peroxisomal PRDX5 protects oligodendrocytes against peroxisomal and mitochondrial oxidative stress.
3. show here how the ligand-observed saturation transfer difference (STD) experiment and the PRDX5 protein-observed 15N-HSQC experiment, two popular NMR screening experiments, can be used to compare the binding modes of analogous fragments
4. PRX5 is either consumed or its production is impaired in severe stroke
5. This study demonistrated that overexpression of mitochondrial PRDX5 protects SH-SY5Y cells against the ROS/RNS-dependent neuronal death induced by MPP+.
6. The promoter region critical for Prx5 gene regulation to which the novel negative transcription regulator, GATA1 binds in human breast cancer cell lines.
7. basal expression of the human PRDX5 gene is regulated by GABP
8. analysis of fragment molecules that bind the human peroxiredoxin 5 active site
9. Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
10. Ets regulates PRDX5 expression through their interaction with HGMB1 protein.
    

PRDX6, Kr. 1q25.1.

https://en.wikipedia.org/wiki/PRDX6

Peroxiredoxin-6 is a protein that in humans is encoded by the PRDX6 gene.[5][6] It is a member of the peroxiredoxin family of antioxidant enzymes.

The protein encoded by this gene is a member of the thiol-specific antioxidant protein family. This protein is a bifunctional enzyme with two distinct active sites. It is involved in redox regulation of the cell; it can reduce H(2)O(2) and short chain organic, fatty acid, and phospholipid hydroperoxides. It may play a role in the regulation of phospholipid turnover as well as in protection against oxidative injury.[6]

PubMed Gene PRDX6, kr.1q25.1.

Also known as

PRX; p29; AOP2; 1-Cys; NSGPx; aiPLA2; HEL-S-128m

Summary

The protein encoded by this gene is a member of the thiol-specific antioxidant protein family. This protein is a bifunctional enzyme with two distinct active sites. It is involved in redox regulation of the cell; it can reduce H(2)O(2) and short chain organic, fatty acid, and phospholipid hydroperoxides. It may play a role in the regulation of phospholipid turnover as well as in protection against oxidative injury. [provided by RefSeq, Jul 2008]

Related articles in PubMed

1. Peroxiredoxin-6 Negatively Regulates Bactericidal Activity and NF-κB Activity by Interrupting TRAF6-ECSIT Complex. Min Y, et al. Front Cell Infect Microbiol, 2017. PMID 28393051, Free PMC Article
2. Peroxiredoxin 6 in the repair of peroxidized cell membranes and cell signaling. Fisher AB. Arch Biochem Biophys, 2017 Mar 1. PMID 27932289
3. Crystal structures of human peroxiredoxin 6 in different oxidation states. Kim KH, et al. Biochem Biophys Res Commun, 2016 Sep 2. PMID 27353378
4. Peroxiredoxin 6 attenuates ischemia‑ and hypoxia‑induced liver damage of brain‑dead donors. Tu Q, et al. Mol Med Rep, 2016 Jan. PMID 26647763, Free PMC Article
5. Peroxiredoxin 6 Is a Crucial Factor in the Initial Step of Mitochondrial Clearance and Is Upstream of the PINK1-Parkin Pathway. Ma S, et al. Antioxid Redox Signal, 2016 Mar 20. PMID 26560306
   

See all (125) citations in PubMed

GeneRIFs: Gene References Into Functions

1. PRDX6 inhibited the carcinogenesis of hepatocellular carcinoma, and the calcium-independent phospholipase A2 activity of PRDX6 promoted cancer cell death induced by TNF-alpha.
2. the data demonstrate that Prdx6 interrupts the formation of TRAF6-ECSIT complex induced by TLR4 stimulation, leading to suppression of bactericidal activity because of inhibited mROS production in mitochondria and the inhibition of NF-kappaB activation in the cytoplasm.
3. Thus far only the crystal structure of Prx in the oxidized state has been reported. In this study, we present the crystal structures of human Prx6 in the reduced (SH) and the sulfinic acid (SO2H) forms.
4. Peroxiredoxin 6 has a role in the repair of peroxidized cell membranes and cell signaling [review]
5. PRDX6-anion exchanger 1 interaction contributes to the maintenance of anion exchanger 1 during cellular stress such as during metabolic acidosis.
6. Prdx6 is a complete enzyme comprising both PLA2and LPCAT activities
7. Our study provides new insight into the initial regulatory mechanisms of mitophagy and reveals the protective role of PRDX6 in the clearance of damaged mitochondria.
8. Thr can substitute for Ser for the enzymatic activities of Prdx6 but not for its targeting to LB. These results confirm an important role for LB Prdx6 in the degradation and remodeling of lung surfactant phosphatidylcholine.
9. Prdx6 and its PLA2 activity have a protective role in donors after brain death livers.
10. PRDX6 may serve as a biomarker for traumatic brain injury and that autoimmune profiling is a viable strategy for the discovery of novel biomarkers
    

Haku PubMed ”PRDX gene” 22.10.2017

Hain pubMed tiedot vain kuudesta ihmisgeenistä PRDX. Wikipedia katsoi laajemmin kasveja ja muuta luomakuntaa.