Top Level Name

  ⌊ Superfamily (core) Peroxiredoxin

Family known
Total 100% <100% Family unknown
Functional domains 12239 0 0 12239
UniProtKB 68415 0 0 68415
GI 123093 0 0 123093
Structures 195
Reactions 0
Functional domains of this superfamily were last updated on Nov. 22, 2017
New functional domains were last added to this superfamily on Aug. 19, 2012

Peroxiredoxins (Prxs) are abundant, ubiquitous proteins involved in antioxidant defense and regulation of cell signaling pathways. Prxs are found across all organisms with the single known exception of Borrelia species. Mammals express six different Prxs from distinct genes (Prx I-Prx VI), and E. coli expresses three (AhpC, Tpx and BCP). The broad distribution of Prxs and high expression levels suggest they are an ancient and important enzyme superfamily; they are among the top ten most abundant E. coli proteins, and typically comprise ~0.1 to 1% of the total cellular proteins in mammalian cells. In mammals, Prxs have been implicated in regulating cell proliferation, differentiation, cell death, and intracellular signaling. Prxs have also been shown to be aberrantly expressed in cancer and to impact the radiation sensitivity of cells. In bacteria, AhpC acts as the primary enzyme responsible for the reduction of endogenously-generated H2O2, with catalase becoming important for protection against intracellular H2O2 levels around 5 μM or higher. And in plants, Prxs protect the photosynthetic apparatus from oxidative damage. Prxs incorporate a variant of the thioredoxin fold, utilizing a peroxidatic cysteine (Cp) to initiate catalysis. The Cp is found in a (T/S)xxC motif, which corresponds to the CxxC motif of the classic thioredoxin fold. The positively charged guanidino group of a conserved arginine (replaces the cis-proline of the other members of the thioredoxin fold) helps to lower the Cp pKa. A second, non-conserved cysteine called the "resolving Cys" (Cr) can participate in catalysis, but is not necessary. The Cr may come from the same Prx on the same chain or on the other subunit of a B-type dimer (2-Cys mechanism) or it can be supplied by a different protein or small molecule (1-Cys mechanism). This may include Trx and AhpF. Subgroups of Prxs have been defined based on previously published structural and functional site characterizations (Hall et al. 2010, Nelson et al. 2011): AhpC-Prx1 (also known as the “typical 2-Cys” Prxs); BCP-PrxQ (for Escherichia coli BCP and plant PrxQ); Tpx (for E. coli Tpx); Prx5 (for Homo sapiens Prx5); Prx6 (for H. sapiens Prx6, sometimes called the "1-Cys" group); and AhpE (for Mycobacterium tuberculosis AhpE).

Wood ZA, Schroder E, Robin Harris J, Poole LB

Structure, mechanism and regulation of peroxiredoxins

▸ Abstract

Trends Biochem Sci 2003;28(1):32-40 | PubMed ID: 12517450

Poole LB

The catalytic mechanism of peroxiredoxins

▸ Abstract

Subcell Biochem 2007;44(None):61-81 | PubMed ID: 18084890

Hall A, Nelson K, Poole LB, Karplus PA.

Structure-based insights into the catalytic power and conformational dexterity of peroxiredoxins.

▸ Abstract

Antioxid Redox Signal. 2011;15(3):795-815 | PubMed ID: 20969484

Nelson KJ, Knutson ST, Soito L, Klomsiri C, Poole LB, Fetrow JS.

Analysis of the peroxiredoxin family: using active-site structure and sequence information for global classification and residue analysis.

▸ Abstract

Proteins 2011;79(3):947-964 | PubMed ID: 21287625

Kang SW, Rhee SG, Chang TS, Jeong W, Choi MH

2-Cys peroxiredoxin function in intracellular signal transduction: therapeutic implications.

▸ Abstract

Trends Mol Med 2005;11(12):571-578 | PubMed ID: 16290020

Link AJ, Robison K, Church GM

Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12

▸ Abstract

Electrophoresis 1997;18(8):1259-1313 | PubMed ID: 9298646

Poole LB, Nelson KJ

Discovering mechanisms of signaling-mediated cysteine oxidation

▸ Abstract

Curr Opin Chem Biol 2008;12(1):18-24 | PubMed ID: 18282483

Rouhier N, Jacquot JP

The plant multigenic family of thiol peroxidases

▸ Abstract

Free Radic Biol Med 2005;38(11):1413-1421 | PubMed ID: 15890615

Seaver LC, Imlay JA

Alkyl hydroperoxide reductase is the primary scavenger of endogenous hydrogen peroxide in Escherichia coli

▸ Abstract

J Bacteriol 2001;183(24):7173-7181 | PubMed ID: 11717276

Veal EA, Day AM, Morgan BA

Hydrogen peroxide sensing and signaling

▸ Abstract

Mol Cell 2007;26(1):1-14 | PubMed ID: 17434122

Zhang B, Wang Y, Su Y

Peroxiredoxins, a novel target in cancer radiotherapy

▸ Abstract

Cancer Lett 2009;286(2):154-160 | PubMed ID: 19500902

No notes.

Sequence Similarity Networks

Download a Sequence Similarity Network of this superfamily (XGMML format ).

Network downloads are XGMML files that are readable by program such as Cytoscape. In these networks, nodes represent proteins and edges represent pairwise similarities better than a given edge-score cutoff. The edge score is either a bit score for full networks or mean E values for a Repnet. Additionally, these networks contain several attributes with data from the SFLD.

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List of files included in the download. A detailed list of included node attributes, their definitions, and their uses [revised: 1/24/2014].

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Multiple Sequence Alignment

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Multiple Sequence Alignment

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Data Type All (#) Known (#) Unknown (#)
Full length FASTA (12239) (0) (12239)
Complete annotation (.tsv) (12239) (0) (12239)
Annotation suitable for Excel ® (.tsv) (12239) (0) (12239)
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Cutoff Value
The least significant edge-score at which pairwise similarities are included in the network. A bit score for the full network, or a mean E value for the Repnet.
XGMML format
Open in Cytoscape via:
 →Network (multiple file types)
Download the annotation of all sequences as shown in the table below as a ͟Tab ͟Separated ͟Value (TSV) file. This file can be imported into a spreadsheet application.
Full length FASTA
Full length sequences in FASTA format.
Functional Domain FASTA
Sequences of the Functional Domain in FASTA format.
Complete annotation
Download complete annotation of sequences sets of this superfamily as a ͟Tab ͟Separated ͟Value (TSV) file. This file has all data but cell size can exceed the maximum supported by spreadsheet programs (such as Microsoft Excel ®).
Spreadsheet ready annotation
Annotation of sequences sets of this superfamily in a ͟Tab ͟Separated ͟Value (TSV) file. This file can be imported into a spreadsheet application. Cells which exceed the allowed spreadsheet maximum (32.5K) are preceded by the word "Truncated" and clipped short.
Total number of functional domains in this group.
Number of Functional Domains that have been manually or automatically been assigned to a family.
Number of Functional Domains that have not been assigned to a family.
Number of structures available from the PDB for members of this group.
Number of Functional Domains with 100% of Conserved Residues
Number of Functional Domains with less than 100% Conserved Residues
Depth of the multi-level Subgroup hierarchy.