Summary: Glutaredoxin

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

Wikipedia: Glutaredoxin
Pfam
InterPro

This is the Wikipedia entry entitled "Glutaredoxin". More...

The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.

Does Pfam agree with the content of the Wikipedia entry ?

Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.

Editing Wikipedia articles

Before you edit for the first time

Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.

You should take a few minutes to view the following pages:

How your contribution will be recorded

Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.

If you have problems editing a particular page, contact us at pfam-help@sanger.ac.uk and we will try to help.

Contact us

The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.

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.

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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...

Loading domain graphics...

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

Viewing

You can see the alignments as HTML or in three different sequence viewers:

jalview: a Java applet developed at the University of Dundee. You will need Java installed before running jalview
HTML: an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
PP/Heatmap: an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.

Reformatting

You can download (or view in your browser) a text representation of a Pfam alignment in various formats:

Selex
Stockholm
FASTA
MSF

You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.

Downloading

You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.

View options

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)
Jalview	View	View	View	View	View	View	View	View	View
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:

download the raw HMM for this family

Species distribution

Sunburst
Tree

Sunburst controls

Hide

Weight segments by...

number of sequences
number of species

Change the size of the sunburst

Small

Large

Colour assignments

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Selections

Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.

How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:

superkingdom
kingdom
phylum
class
order
family
genus
species

Colouring and labels

Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.

As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.

Anomalies in the taxonomy tree

There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.

Missing taxonomic levels

Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.

Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".

Sub-species

Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

Too many species/sequences

For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

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.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

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.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
save a plain text representation of the tree

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

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

Redoxin Pyr_redox_2 GST_C_3 GST_C_3 Glutaredoxin

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.

Loading structure mapping...

Family: Glutaredoxin (PF00462)

Jump to...