Top Level Name

  ⌊ Superfamily (core) Glutathione Transferase (cytosolic)

Total 100% <100% Family unknown
Functional domains 13097
UniProtKB 65594 0 0 65594
GI 130013 0 0 130013
Structures 483
Reactions 0
Functional domains of this superfamily were last updated on June 27, 2017
New functional domains were last added to this superfamily on Oct. 10, 2012

The cytosolic glutathione transferases (cytGSTs) are known for adding the tripeptide glutathione (GSH) to substrate compounds. The archetypal role of cytGSTs is in mammalian enzymatic detoxification, in which electrophilic small molecules are modified by the addition of GSH, making compounds more soluble. Glutathionylated compounds are recognized by transporters and exported from the cell. It is known that cytGSTs also catalyze other reactions like reduction of peroxides in which the glutathionylated compound is an intermediate. Certain bacteria use cytGSTs to exploit various compounds as a carbon source. All cytGSTs catalyze the nucleophilic attack of GSH on a substrate compound. The activation of GSH is achieved in part by interactions with a residue in the enzyme active site: a tyrosine ("AMPS" subgroup), or a serine or cysteine ("Main" subgroup). Cytosolic GSTs incorporate a distant variant of the thioredoxin fold. The great variation of reactions of the cytGSTs may be categorized into "reaction types" by similarities in chemistry. These reaction types range from nucleophilic substitution (SN2) and nucleophilic aromatic substitution (such as the well-known CDNB activity) to isomerization reactions.

A chart of the major cytGST reaction types with example reactions can be downloaded here: cytGST Reaction Types

A set of files with sequence and structure similarity networks that include representative network views (50% sequence identity filtered) that can be used as an overall visual guide to the superfamily, and that show where experimentally confirmed reaction types occur. This set of files can be downloaded here: Sequence and Structure Networks

A spreadsheet of cytGSTs that show which experimentally confirmed reaction types occur in representative nodes can be downloaded here: Reaction types in representative nodes

A detailed spreadsheet of cytGSTs in the full networks with experimentally confirmed evidence for GST-like reactions with reaction types, substrates, references, and nodes identifiers in the representative network can be downloaded here: Detailed reaction types and substrates

Armstrong RN

Structure, catalytic mechanism, and evolution of the glutathione transferases

▸ Abstract

Chem Res Toxicol 1997;10(1):2-18 | PubMed ID: 9074797

Jemth P, Mannervik B

Active site serine promotes stabilization of the reactive glutathione thiolate in rat glutathione transferase T2-2. Evidence against proposed sulfatase activity of the corresponding human enzyme

▸ Abstract

J Biol Chem 2000;275(12):8618-8624 | PubMed ID: 10722701

Copley SD

Evolution of a metabolic pathway for degradation of a toxic xenobiotic: the patchwork approach

▸ Abstract

Trends Biochem Sci 2000;25(6):261-265 | PubMed ID: 10838562

Sheehan D, Meade G, Foley VM, Dowd CA

Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily

▸ Abstract

Biochem J 2001;360(None):1-16 | PubMed ID: 11695986

Mashiyama ST, Malabanan MM, Akiva E, Bhosle R, Branch MC, Hillerich B, Jagessar K, Kim J, Patskovsky Y, Seidel RD, Stead M, Toro R, Vetting MW, Almo SC, Armstrong RN, Babbitt PC

Large-scale determination of sequence, structure, and function relationships in cytosolic glutathione transferases across the biosphere

▸ Abstract

PLoS Biol 2014;12(4):None-None | PubMed ID: 24756107


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.

Select any restriction to apply to your network.
Maximum number of edges:
250K 500K 750K ALL
edge-score cutoff

Full sequence similarity network is not available for this superfamily due to its size.
Repnet: 90% ID (25-Apr-2016) Repnet: 50% ID (1-Apr-2016)

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

Although the download speed has improved please keep in mind that network files can be quite large. We are currently working on improving the network download and finding ways to make large networks manageable. Please see How to increase memory for Cytoscape.

Multiple Sequence Alignment

View the alignment of a representative set of sequences of this superfamily using

Multiple Sequence Alignment

Align one or multiple sequences to the alignment of a representative set of sequences of this superfamily.
Enter FASTA formatted sequence(s) : and view results using


Data Type All (#) Known (#) Unknown (#)
Full length FASTA (13097) (0) (13097)
Complete annotation (.tsv) (13097) (0) (13097)
Annotation suitable for Excel ® (.tsv) (13097) (0) (13097)
Clear form

Some of these files can be quite large, please be patient during the download.

To identify your sequence later, please make sure to provide a header line starting with '>' for each sequence. Empty headers are allowed, but a header line is always required.
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.