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1199  structures 4047  species 0  interactions 34909  sequences 434  architectures

Family: GST_N (PF02798)

Summary: Glutathione S-transferase, N-terminal domain

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

This is the Wikipedia entry entitled "Glutathione S-transferase". More...

Glutathione S-transferase Edit Wikipedia article

The Glutathione S-transferase (GST) family of enzymes comprises a long list of cytosolic, mitochondrial, and microsomal proteins which are capable of multiple reactions with a multitude of substrates, both endogenous and xenobiotic.


Families of GST

  • Mammalian
    • Alpha
      • A1-1
      • A2-2
      • A3-3
      • A4-4
      • hGST5.8 (putative)
    • Mu
      • M1-1
    • Pi
      • P1-1
    • Theta
    • Zeta
    • Omega


Structure of GSTs

Mammalian cytosolic GSTs are homodimeric, and the monomers are in the range of 22-29 kDa. They are active over a wide variety of substrates with considerable overlap.

GSTs and Biotransformation

Glutathione S-transferases are considered, among several others, to contribute to the phase II biotransformation of xenobiotics. Drugs, poisons, and other compounds not traditionally listed in either groups are usually somewhat modified by the phase I and/or phase II mechanisms, and finally exreted from the body. GSTs contribute to this type of metabolism by conjugating these compounds (often electrophilic and somewhat lipophilic in nature) with reduced glutathione to facilitate dissolution in the aqueous cellular and extracelluar media, and from there, out of the body.

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.

Glutathione S-transferase, N-terminal domain Provide feedback

Function: conjugation of reduced glutathione to a variety of targets. Also included in the alignment, but not GSTs: S-crystallins from squid (similarity to GST previously noted); eukaryotic elongation factors 1-gamma (not known to have GST activity and similarity not previously recognised); HSP26 family of stress-related proteins including auxin-regulated proteins in plants and stringent starvation proteins in E. coli (not known to have GST activity and similarity not previously recognised). The glutathione molecule binds in a cleft between the N- and C-terminal domains - the catalytically important residues are proposed to reside in the N-terminal domain [1].

Literature references

  1. Nishida M, Harada S, Noguchi S, Satow Y, Inoue H, Takahashi K; , J Mol Biol 1998;281:135-147.: Three-dimensional structure of Escherichia coli glutathione S-transferase complexed with glutathione sulfonate: catalytic roles of Cys10 and His106. PUBMED:9680481 EPMC:9680481


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR004045

In eukaryotes, glutathione S-transferases (GSTs) participate in the detoxification of reactive electrophilic compounds by catalysing their conjugation to glutathione. The GST domain is also found in S-crystallins from squid, and proteins with no known GST activity, such as eukaryotic elongation factors 1-gamma and the HSP26 family of stress-related proteins, which include auxin-regulated proteins in plants and stringent starvation proteins in Escherichia coli. The major lens polypeptide of Cephalopoda is also a GST [ PUBMED:9074797 , PUBMED:10783391 , PUBMED:11035031 , PUBMED:10416260 ].

Bacterial GSTs of known function often have a specific, growth-supporting role in biodegradative metabolism: epoxide ring opening and tetrachlorohydroquinone reductive dehalogenation are two examples of the reactions catalysed by these bacterial GSTs. Some regulatory proteins, like the stringent starvation proteins, also belong to the GST family [ PUBMED:11327815 , PUBMED:9045797 ]. GST seems to be absent from Archaea in which gamma-glutamylcysteine substitute to glutathione as major thiol.

Soluble GSTs activate glutathione (GSH) to GS-. In many GSTs, this is accomplished by a Tyr at H-bonding distance from the sulphur of GSH. These enzymes catalyse nucleophilic attack by reduced glutathione (GSH) on nonpolar compounds that contain an electrophilic carbon, nitrogen, or sulphur atom [ PUBMED:16399376 ].

Glutathione S-transferases form homodimers, but in eukaryotes can also form heterodimers of the A1 and A2 or YC1 and YC2 subunits. The homodimeric enzymes display a conserved structural fold, with each monomer composed of two distinct domains [ PUBMED:12211029 ]. The N-terminal domain forms a thioredoxin-like fold that binds the glutathione moiety, while the C-terminal domain contains several hydrophobic alpha-helices that specifically bind hydrophobic substrates.

This entry represents the N-terminal domain of GST.

Gene Ontology

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

Domain organisation

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

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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 and the UniProtKB sequence database. More...

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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
(22)
Full
(34909)
Representative proteomes UniProt
(111975)
RP15
(5459)
RP35
(16077)
RP55
(30652)
RP75
(50341)
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PP/heatmap 1            

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

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(22)
Full
(34909)
Representative proteomes UniProt
(111975)
RP15
(5459)
RP35
(16077)
RP55
(30652)
RP75
(50341)
Alignment:
Format:
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Sequence:
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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
(22)
Full
(34909)
Representative proteomes UniProt
(111975)
RP15
(5459)
RP35
(16077)
RP55
(30652)
RP75
(50341)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped 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 View help on the curation process

Seed source: Overington
Previous IDs: gluts;
Type: Domain
Sequence Ontology: SO:0000417
Author: Eddy SR , Griffiths-Jones SR
Number in seed: 22
Number in full: 34909
Average length of the domain: 74.3 aa
Average identity of full alignment: 25 %
Average coverage of the sequence by the domain: 30.93 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.9 20.9
Trusted cut-off 20.9 20.9
Noise cut-off 20.8 20.8
Model length: 76
Family (HMM) version: 23
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

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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 GST_N domain has been found. There are 1199 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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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A044T8Y6 View 3D Structure Click here
A0A044UM60 View 3D Structure Click here
A0A077ZC56 View 3D Structure Click here
A0A0B5E2M0 View 3D Structure Click here
A0A0B5E8V1 View 3D Structure Click here
A0A0B5EA67 View 3D Structure Click here
A0A0B5EC24 View 3D Structure Click here
A0A0D2DF47 View 3D Structure Click here
A0A0D2DKU7 View 3D Structure Click here
A0A0D2EQW3 View 3D Structure Click here
A0A0D2ES19 View 3D Structure Click here
A0A0D2F5U3 View 3D Structure Click here
A0A0D2FAX6 View 3D Structure Click here
A0A0D2G4E3 View 3D Structure Click here
A0A0D2GCJ5 View 3D Structure Click here
A0A0D2GMS2 View 3D Structure Click here
A0A0D2GQ99 View 3D Structure Click here
A0A0D2H266 View 3D Structure Click here
A0A0G2JTB1 View 3D Structure Click here
A0A0G2JZ09 View 3D Structure Click here
A0A0G2JZV9 View 3D Structure Click here
A0A0G2K4Q5 View 3D Structure Click here
A0A0H3GIS7 View 3D Structure Click here
A0A0H3GM02 View 3D Structure Click here
A0A0H3GP63 View 3D Structure Click here
A0A0H3GQD2 View 3D Structure Click here
A0A0H3GUF4 View 3D Structure Click here
A0A0H3GVR7 View 3D Structure Click here
A0A0H3GZ22 View 3D Structure Click here
A0A0H3H341 View 3D Structure Click here
A0A0H5S7P0 View 3D Structure Click here
A0A0K0DY26 View 3D Structure Click here
A0A0K0DY27 View 3D Structure Click here
A0A0K0EK30 View 3D Structure Click here
A0A0K0EK34 View 3D Structure Click here
A0A0K0EK35 View 3D Structure Click here
A0A0N4UIN0 View 3D Structure Click here
A0A0N4ULU7 View 3D Structure Click here
A0A0N4UQM7 View 3D Structure Click here
A0A0P0VCV3 View 3D Structure Click here