Summary: Glutaredoxin

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Wikipedia: Glutaredoxin
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Glutaredoxin Edit Wikipedia article

Glutaredoxin

Identifiers

Symbol

Glutaredoxin

Pfam clan

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Glutaredoxins^[1]^[2]^[3] are small redox enzymes of approximately one hundred amino-acid residues that use glutathione as a cofactor. Glutaredoxins are oxidized by substrates, and reduced non-enzymatically by glutathione. In contrast to thioredoxins, which are reduced by thioredoxin reductase, no oxidoreductase exists that specifically reduces glutaredoxins. Instead, glutaredoxins are reduced by the oxidation of glutathione. Oxidized glutathione is then regenerated by glutathione reductase. Together these components compose the glutathione system.^[4]

Like thioredoxin, which functions in a similar way, glutaredoxin possesses an active centre disulfide bond.^[5] It exists in either a reduced or an oxidized form where the two cysteine residues are linked in an intramolecular disulfide bond. Glutaredoxins function as electron carriers in the glutathione-dependent synthesis of deoxyribonucleotides by the enzyme ribonucleotide reductase.^[4] Moreover, GRX act in antioxidant defence by reducing dehydroascorbate, peroxiredoxins, and methionine sulfoxide reductase. Beside their function in antioxidant defence, bacterial and plant GRX were shown to bind iron-sulfur clusters and to deliver the cluster to enzymes on demand.^[6]

GRXs in viruses

Glutaredoxin has been sequenced in a variety of species. On the basis of extensive sequence similarity, it has been proposed^[7] that Vaccinia virus protein O2L is, it seems, a glutaredoxin. Bacteriophage T4 thioredoxin seems to be evolution-related. In position 5 of the pattern T4, thioredoxin has Val instead of Pro.

GRXs in plants

Approximately 30 GRX isoforms are described in the model plant Arabidopsis thaliana and 48 in Oryza sativa L. According to their redox-active centre, they are subgrouped in six classes of the CSY[C/S]-, CGFS-, CC-type and 3 groups with additional domain of unknown function. The CC-type GRXs are only found in higher plants. In Arabidopsis GRXs are involved in flower development and Salicylic acid signalling.^[6]

Subfamilies

Glutaredoxin subgroup InterPro: IPR014025

Human proteins containing this domain

GLRX; GLRX2; GLRX3; GLRX5; PTGES2

References

^ Holmgren A, Gleason FK (1988). "Thioredoxin and related proteins in procaryotes". FEMS Microbiol. Rev. 4 (4): 271–297. doi:10.1111/j.1574-6968.1988.tb02747.x. PMID 3152490.
^ Holmgren A (1988). "Thioredoxin and glutaredoxin: small multi-functional redox proteins with active-site disulfide bonds". Biochem. Soc. Trans. 16 (2): 95–96. PMID 3286320.
^ Holmgren A (1989). "Thioredoxin and glutaredoxin systems". J. Biol. Chem. 264 (24): 13963–13966. PMID 2668278.
^ ^a ^b Holmgren A, Fernandes AP (2004). "Glutaredoxins: glutathione-dependent redox enzymes with functions far beyond a simple thioredoxin backup system". Antioxid. Redox Signal. 6 (1): 63–74. doi:10.1089/152308604771978354. PMID 14713336.
^ Nilsson L, Foloppe N (2004). "The glutaredoxin -C-P-Y-C- motif: influence of peripheral residues". Structure. 12 (2): 289–300. doi:10.1016/j.str.2004.01.009. PMID 14962389.
^ ^a ^b Rouhier N, Lemaire SD, Jacquot JP (2008). "The role of glutathione in photosynthetic organisms: emerging functions for glutaredoxins and glutathionylation". Annu Rev Plant Biol. 59: 143–66. doi:10.1146/annurev.arplant.59.032607.092811. PMID 18444899.
^ Johnson GP, Goebel SJ, Perkus ME, Davis SW, Winslow JP, Paoletti E (1991). "Vaccinia virus encodes a protein with similarity to glutaredoxins". Virology. 181 (1): 378–381. doi:10.1016/0042-6822(91)90508-9. PMID 1994586.

External links

Enzyme database entry
Glutaredoxins at the US National Library of Medicine Medical Subject Headings (MeSH)

v t e Other oxidoreductases (EC 1.15-1.21)

1.15: Acting on superoxide as acceptor	Superoxide dismutase SOD1 SOD2 SOD3

1.16: Oxidizing metal ions	Ceruloplasmin

1.17: Acting on CH or CH2 groups	Xanthine oxidase Ribonucleotide reductase 4-Hydroxy-3-methylbut-2-enyl diphosphate reductase

1.18: Acting on iron-sulfur proteins as donors	Nitrogenase

1.19: Acting on reduced flavodoxin as donor	Nitrogenase (flavodoxin)

1.20: Acting on phosphorus or arsenic in donors	Glutaredoxin GLRX GLRX2 GLRX3 GLRX5

1.21: Acting on X-H and Y-H to form an X-Y bond	Isopenicillin N synthase Columbamine oxidase Reticuline oxidase Sulochrin oxidase (+)-bisdechlorogeodin-forming (-)-bisdechlorogeodin-forming Aureusidin synthase Tetrahydrocannabinolic acid synthase Cannabidiolic acid synthase Dichlorochromopyrrolate synthase

v t e Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics

Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

This EC 1.20 enzyme-related article is a stub. You can help Wikipedia by expanding it.

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Glutaredoxin Provide feedback

No Pfam abstract.

Internal database links

SCOOP:	ABC_transp_aux AhpC-TSA ArsC DIM1 DSBA DUF3088 DUF836 DUF953 GST_N GST_N_2 GST_N_3 GST_N_4 HyaE KaiB OST3_OST6 Redoxin SH3BGR Thioredoxin Thioredoxin_2 Thioredoxin_3 Thioredoxin_6 Thioredoxin_7 Thioredoxin_8 Thioredoxin_9 TraF
Similarity to PfamA using HHSearch:	Thioredoxin GST_N ArsC SH3BGR DUF836 Thioredoxin_2 Thioredoxin_3 GST_N_2 GST_N_3 TraF Thioredoxin_9

External database links

HOMSTRAD:	thiored
PROSITE:	PDOC00173
SCOP:	1kte

This tab holds annotation information from the InterPro database.

InterPro entry IPR002109

Glutaredoxins [PUBMED:3152490, PUBMED:3286320, PUBMED:2668278], also known as thioltransferases (disulphide reductases, are small proteins of approximately one hundred amino-acid residues which utilise glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system [PUBMED:14713336].

Glutaredoxin functions as an electron carrier in the glutathione-dependent synthesis of deoxyribonucleotides by the enzyme ribonucleotide reductase. Like thioredoxin (TRX), which functions in a similar way, glutaredoxin possesses an active centre disulphide bond [PUBMED:14962389]. It exists in either a reduced or an oxidized form where the two cysteine residues are linked in an intramolecular disulphide bond. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH -> GSH reductase -> GSH -> GRX -> protein substrates [PUBMED:9860827, PUBMED:10493864, PUBMED:15814611, PUBMED:15706083]. By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress.

Glutaredoxin has been sequenced in a variety of species. On the basis of extensive sequence similarity, it has been proposed [PUBMED:1994586] that Vaccinia virus protein O2L is most probably a glutaredoxin. Finally, it must be noted that Bacteriophage T4 thioredoxin seems also to be evolutionary related. In position 5 of the pattern T4 thioredoxin has Val instead of Pro.

This entry represents Glutaredoxin.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Molecular function	protein disulfide oxidoreductase activity (GO:0015035)
Molecular function	electron transfer activity (GO:0009055)
Biological process	cell redox homeostasis (GO:0045454)

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan Thioredoxin (CL0172), which has the following description:

This clan contains families related to the thioredoxin family. Thioredoxins are small enzymes that are involved in redox reactions via the reversible oxidation of an active centre disulfide bond. The thioredoxin fold consists of a 3 layer alpha/beta/alpha sandwich and a central beta sheet.

The clan contains the following 62 members:

2Fe-2S_thioredx AhpC-TSA AhpC-TSA_2 ArsC ArsD Calsequestrin DIM1 DSBA DUF1223 DUF1462 DUF1525 DUF1687 DUF2703 DUF2847 DUF4174 DUF836 DUF899 DUF953 ERp29_N GILT Glutaredoxin GSHPx GST_N GST_N_2 GST_N_3 GST_N_4 GST_N_5 HyaE KaiB L51_S25_CI-B8 MRP-S23 MRP-S25 OST3_OST6 Phe_hydrox_dim Phosducin QSOX_Trx1 Rdx Redoxin SCO1-SenC SelP_N Sep15_SelM SH3BGR T4_deiodinase Thioredox_DsbH Thioredoxin Thioredoxin_11 Thioredoxin_12 Thioredoxin_13 Thioredoxin_14 Thioredoxin_15 Thioredoxin_16 Thioredoxin_2 Thioredoxin_3 Thioredoxin_4 Thioredoxin_5 Thioredoxin_6 Thioredoxin_7 Thioredoxin_8 Thioredoxin_9 Tom37 TraF YtfJ_HI0045

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
UniProt: alignment generated by searching the UniProtKB sequence database using the family HMM
NCBI: alignment generated by searching the NCBI sequence database using the family HMM
meta: alignment generated by searching the metagenomics sequence database using the family HMM

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

	Seed (243)	Full (23568)	Representative proteomes				UniProt (54868)	NCBI (71708)	Meta (4872)
	Seed (243)	Full (23568)	RP15 (6015)	RP35 (15106)	RP55 (22440)	RP75 (30664)	UniProt (54868)	NCBI (71708)	Meta (4872)
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HTML	View
PP/heatmap	₁

¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (243)	Full (23568)	Representative proteomes				UniProt (54868)	NCBI (71708)	Meta (4872)
	Seed (243)	Full (23568)	RP15 (6015)	RP35 (15106)	RP55 (22440)	RP75 (30664)	UniProt (54868)	NCBI (71708)	Meta (4872)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

	Seed (243)	Full (23568)	Representative proteomes				UniProt (54868)	NCBI (71708)	Meta (4872)
	Seed (243)	Full (23568)	RP15 (6015)	RP35 (15106)	RP55 (22440)	RP75 (30664)	UniProt (54868)	NCBI (71708)	Meta (4872)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download	Download	Download
Gzipped	Download	Download	Download	Download	Download	Download	Download	Download	Download

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation

Seed source:

Prosite & Pfam-B_3081 (Release 8.0)

Previous IDs:

glutaredoxin;

Type:

Domain

Sequence Ontology:

SO:0000417

Author:

Finn RD

, Bateman A

Number in seed:

243

Number in full:

23568

Average length of the domain:

62.50 aa

Average identity of full alignment:

24 %

Average coverage of the sequence by the domain:

39.16 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	22.8	22.8
Trusted cut-off	22.8	22.8
Noise cut-off	22.7	22.7

Model length:

60

Family (HMM) version:

24

Download:

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Species distribution

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Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

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We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

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Interactions

There are 5 interactions for this family. More...

Pyr_redox_2 Glutaredoxin GST_C_3 Redoxin GST_C_3

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Glutaredoxin domain has been found. There are 135 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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Family: Glutaredoxin (PF00462)

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