Summary: Glutathione peroxidase

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Wikipedia: Glutathione peroxidase
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Glutathione peroxidase Edit Wikipedia article

Glutathione peroxidase

Crystallographic structure of bovine glutathione peroxidase 1.^[1]

Identifiers

Databases

PDB structures

AmiGO / EGO

Search
PMC	articles
PubMed	articles
NCBI	proteins

Glutathione peroxidase

Identifiers

Symbol

GSHPx

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

Glutathione peroxidase (GPx) (EC 1.11.1.9) is the general name of an enzyme family with peroxidase activity whose main biological role is to protect the organism from oxidative damage. The biochemical function of glutathione peroxidase is to reduce lipid hydroperoxides to their corresponding alcohols and to reduce free hydrogen peroxide to water.

[edit] Isozymes

Several isozymes are encoded by different genes, which vary in cellular location and substrate specificity. Glutathione peroxidase 1 (GPx1) is the most abundant version, found in the cytoplasm of nearly all mammalian tissues, whose preferred substrate is hydrogen peroxide. Glutathione peroxidase 4 (GPx4) has a high preference for lipid hydroperoxides; it is expressed in nearly every mammalian cell, though at much lower levels. Glutathione peroxidase 2 is an intestinal and extracellular enzyme, while glutathione peroxidase 3 is extracellular, especially abundant in plasma.^[2] So far, eight different isoforms of glutathione peroxidase (GPx1-8) have been identified in humans.

Gene	Locus	Enzyme
GPX1	Chr. 3 p21.3	glutathione peroxidase 1
GPX2	Chr. 14 q24.1	glutathione peroxidase 2 (gastrointestinal)
GPX3	Chr. 5 q23	glutathione peroxidase 3 (plasma)
GPX4	Chr. 19 p13.3	glutathione peroxidase 4 (phospholipid hydroperoxidase)
GPX5	Chr. 6 p21.32	glutathione peroxidase 5 (epididymal androgen-related protein)
GPX6	Chr. 6 p21	glutathione peroxidase 6 (olfactory)
GPX7	Chr. 1 p32	glutathione peroxidase 7
GPX8	Chr. 5 q11.2	glutathione peroxidase 8 (putative)

[edit] Reaction

The main reaction that glutathione peroxidase catalyzes is:

2GSH + H₂O₂ → GS–SG + 2H₂O

where GSH represents reduced monomeric glutathione, and GS–SG represents glutathione disulfide. The mechanism involves oxidation of the selenol of a selenocysteine residue by hydrogen peroxide. This process gives the derivative with a seleninic acid (RSeOH) group. The selenenic acid is then converted back to the selenol by a two step process that begins with reaction with GSH to form the GS-SeR and water. A second GSH molecule reduces the GS-SeR intermediate back to the selenol, releasing GS-SG as the by-product. A simplified representation is shown below:^[3]

RSeH + H₂O₂ → RSeOH + H₂O

RSeOH + GSH → GS-SeR + H₂O

GS-SeR + GSH → GS-SG + RSeH

Glutathione reductase then reduces the oxidized glutathione to complete the cycle:

GS–SG + NADPH + H⁺ → 2 GSH + NADP⁺.

[edit] Structure

Mammalian GPx1, GPx2, GPx3, and GPx4 have been shown to be selenium-containing enzymes, whereas GPx6 is a selenoprotein in humans with cysteine-containing homologues in rodents. GPx1, GPx2, and GPx3 are homotetrameric proteins, whereas GPx4 has a monomeric structure. As the integrity of the cellular and subcellular membranes depends heavily on glutathione peroxidase, its antioxidative protective system itself depends heavily on the presence of selenium.

[edit] Species distribution

Mice genetically engineered to lack glutathione peroxidase 1 (Gpx1 knockout mice) are grossly phenotypically normal and have normal lifespans, indicating this enzyme is not critical for life. However, Gpx1 -/- mice develop cataracts at an early age and exhibit defects in muscle satellite cell proliferation.^[2]

However, glutathione peroxidase 4 knockout mice die during early embryonic development.^[2]

Some evidence, though, indicates reduced levels of glutathione peroxidase 4 can increase life expectancy in mice.^[4]

No information is available on knockouts of the other isozymes.

The bovine erythrocyte enzyme has a molecular weight of 84 kDa.

[edit] Discovery

Glutathione peroxidase was discovered in 1957 by Gordon C. Mills.^[5]

[edit] Human proteins containing this domain

GPX1; GPX2; GPX3; GPX4; GPX5;

[edit] References

^ PDB 1GP1; Epp O, Ladenstein R, Wendel A (June 1983). "The refined structure of the selenoenzyme glutathione peroxidase at 0.2-nm resolution". Eur. J. Biochem. 133 (1): 51–69. doi:10.1111/j.1432-1033.1983.tb07429.x. PMID 6852035.
^ ^a ^b ^c 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. doi:10.1016/j.freeradbiomed.2007.03.034. PMID 17640558.
^ Krishna P. Bhabak, Govindasamy Mugesh "Functional Mimics of Glutathione Peroxidase: Bioinspired Synthetic Antioxidants" Acc. Chem. Res., 2010, 43 (11), pp 1408–1419. doi:10.1021/ar100059g
^ Ran Q, Liang H, Ikeno Y (2007). "Reduction in glutathione peroxidase 4 increases life span through increased sensitivity to apoptosis". J. Gerontol. A Biol. Sci. Med. Sci. 62 (9): 932–42. PMID 17895430.
^ MILLS GC (November 1957). "Hemoglobin catabolism. I. Glutathione peroxidase, an erythrocyte enzyme which protects hemoglobin from oxidative breakdown". J. Biol. Chem. 229 (1): 189–97. PMID 13491573. http://www.jbc.org/cgi/reprint/229/1/189.

[edit] See also

Oxidoreductases: peroxidases (EC 1.11)

1.11.1.1-14

Catalase
Cytochrome c peroxidase
Eosinophil peroxidase
Glutathione peroxidase
- GPX 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
Horseradish peroxidase
Lactoperoxidase
Myeloperoxidase
Thyroid peroxidase
Deiodinase
- Iodothyronine deiodinase
- Iodotyrosine deiodinase

1.11.1.15 (peroxiredoxin)

1
2
3
4
5
6

B
enzm
1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
2.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
2.7.10
2.7.11-12
3.1
- - 3.1.3.48
- 2
- 3
- 4
  - 3.4.21
- 5
- 6
- 7
- 22
- 23
- 24
4.1
- 2
- 3
- 4
- 5
- 6
5.1
- 2
- 3
- 4
- 99
6.1-3
- 4
- 5-6

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

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Glutathione peroxidase Provide feedback

No Pfam abstract.

Internal database links

Similarity to PfamA using HHSearch:

AhpC-TSA Redoxin

External database links

PANDIT:	PF00255
PROSITE:	PDOC00396
Pseudofam:	PF00255
SCOP:	1gp1
SYSTERS:	GSHPx

This tab holds annotation information from the InterPro database.

InterPro entry IPR000889

Glutathione peroxidase (GSHPx) (EC) is an enzyme that catalyses the reduction of hydroxyperoxides by glutathione [PUBMED:, PUBMED:7565867]. Its main function is to protect against the damaging effect of endogenously formed hydroxyperoxides. In higher vertebrates, several forms of GSHPx are known, including a ubiquitous cytosolic form (GSHPx-1), a gastrointestinal cytosolic form (GSHPx-GI), a plasma secreted form (GSHPx-P), and an epididymal secretory form (GSHPx-EP). In addition to these characterised forms, the sequence of a protein of unknown function [PUBMED:2771650] has been shown to be evolutionary related to those of GSHPx's.

In filarial nematode parasites, the major soluble cuticular protein (gp29) is a secreted GSHPx, which may provide a mechanism of resistance to the immune reaction of the mammalian host by neutralising the products of the oxidative burst of leukocytes [PUBMED:1631065]. The Escherichia coli protein btuE, a periplasmic protein involved in vitamin B12 transport, is evolutionarily related to GSHPxs, although the significance of this relationship is unclear. The structure of bovine seleno-glutathione peroxidase has been determined [PUBMED:6852035]. The protein belongs to the alpha-beta class, with a 3 layer(aba) sandwich architecture. The catalyic site of GSHPx contains a conserved residue which is either a cysteine or, in many eukaryotic GSHPx, a selenocysteine [PUBMED:2142875].

Gene Ontology

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

Molecular function	glutathione peroxidase activity (GO:0004602)
Biological process	response to oxidative stress (GO:0006979)
Biological process	oxidation-reduction process (GO:0055114)

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 contains the following 45 members:

2Fe-2S_thioredx AhpC-TSA AhpC-TSA_2 ArsC ArsD Calsequestrin DIM1 DSBA DUF1525 DUF1687 DUF2703 DUF4174 DUF836 DUF899 DUF953 ERp29_N Glutaredoxin GSHPx GST_N GST_N_2 GST_N_3 HyaE KaiB MRP-S23 MRP-S25 OST3_OST6 Phosducin Redoxin SCO1-SenC SelP_N SH3BGR T4_deiodinase Thioredox_DsbH Thioredoxin 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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, 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
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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You can see the alignments as HTML or in three different sequence viewers:

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Pfam viewer: an HTML-based viewer that uses DAS to retrieve alignment fragments on request

Reformatting

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

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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 (12)	Full (4817)	Representative proteomes				NCBI (4342)	Meta (2461)
	Seed (12)	Full (4817)	RP15 (446)	RP35 (800)	RP55 (1119)	RP75 (1412)	NCBI (4342)	Meta (2461)
Jalview	View	View	View	View	View	View	View	View
HTML	View	View	View	View	View	View
PP/heatmap	₁	View	View	View	View	View
Pfam viewer	View	View

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

Key: available, not generated, — not available.

Format an alignment

	Seed (12)	Full (4817)	Representative proteomes				NCBI (4342)	Meta (2461)
	Seed (12)	Full (4817)	RP15 (446)	RP35 (800)	RP55 (1119)	RP75 (1412)	NCBI (4342)	Meta (2461)
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 (12)	Full (4817)	Representative proteomes				NCBI (4342)	Meta (2461)
	Seed (12)	Full (4817)	RP15 (446)	RP35 (800)	RP55 (1119)	RP75 (1412)	NCBI (4342)	Meta (2461)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download	Download
Gzipped	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.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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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

Previous IDs:

none

Type:

Family

Author:

Finn RD

Number in seed:

12

Number in full:

4817

Average length of the domain:

104.50 aa

Average identity of full alignment:

45 %

Average coverage of the sequence by the domain:

59.73 %

HMM information

HMM build commands:

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

search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	20.7	20.7
Trusted cut-off	20.7	20.7
Noise cut-off	20.6	20.6

Model length:

108

Family (HMM) version:

14

Download:

download the raw HMM for this family

Species distribution

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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.

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superkingdom
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phylum
class
order
family
genus
species

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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.

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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.

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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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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.

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Interactions

There is 1 interaction for this family. More...

GSHPx

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 GSHPx domain has been found. There are 33 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 seqence.

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Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: GSHPx (PF00255)

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Summary: Glutathione peroxidase

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Glutathione peroxidase Edit Wikipedia article

Contents

[edit] Isozymes

[edit] Reaction

[edit] Structure

[edit] Species distribution

[edit] Discovery

[edit] Human proteins containing this domain

[edit] References

[edit] See also

Glutathione peroxidase Provide feedback

Internal database links

External database links

InterPro entry IPR000889

Gene Ontology

Domain organisation

Pfam Clan

Alignments

Alignment types

Viewing

Reformatting

Downloading

View options

Format an alignment

Download options

External links

HMM logo

Trees

Curation and family details

Curation

HMM information

Species distribution

Sunburst controls

Weight segments by...

Change the size of the sunburst

Colour assignments

Selections

Currently selected:

How the sunburst is generated

Colouring and labels

Anomalies in the taxonomy tree

Missing taxonomic levels

Unmapped species names

Sub-species

Too many species/sequences

Tree controls

Annotation

Download tree

Selected sequences

Species trees

Interactive tree

Interactions

Structures