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13  structures 1592  species 1  interaction 2189  sequences 10  architectures

Family: GCS2 (PF04107)

Summary: Glutamate-cysteine ligase family 2(GCS2)

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The Pfam group coordinates the annotation of Pfam families in Wikipedia, but we have not yet assigned a Wikipedia article to this family. If you think that a particular Wikipedia article provides good annotation, please let us know.

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.

Glutamate-cysteine ligase family 2(GCS2) Provide feedback

Also known as gamma-glutamylcysteine synthetase and gamma-ECS ( EC:6.3.2.2). This enzyme catalyses the first and rate limiting step in de novo glutathione biosynthesis. Members of this family are found in archaea, bacteria and plants. May and Leaver [1] discuss the possible evolutionary origins of glutamate-cysteine ligase enzymes in different organisms and suggest that it evolved independently in different eukaryotes, from an ancestral bacterial enzyme. They also state that Arabidopsis thaliana gamma-glutamylcysteine synthetase is structurally unrelated to mammalian, yeast and Escherichia coli homologues. In plants, there are separate cytosolic and chloroplast forms of the enzyme.

Literature references

  1. May MJ, Leaver CJ; , Proc Natl Acad Sci U S A 1994;91:10059-10063.: Arabidopsis thaliana gamma-glutamylcysteine synthetase is structurally unrelated to mammalian, yeast, and Escherichia coli homologs. PUBMED:7937837 EPMC:7937837


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR006336

Also known as gamma-glutamylcysteine synthetase and gamma-ECS (EC). This enzyme catalyses the first and rate limiting step in de novo glutathione biosynthesis. Members of this family are found in archaea, bacteria and plants. May and Leaver [PUBMED:7937837] discuss the possible evolutionary origins of glutamate-cysteine ligase enzymes in different organisms and suggest that it evolved independently in different eukaryotes, from an ancestral bacterial enzyme. They also state that Arabidopsis thaliana (Mouse-ear cress) gamma-glutamylcysteine synthetase is structurally unrelated to mammalian, yeast and Escherichia coli homologues. In plants, there are separate cytosolic and chloroplast forms of the enzyme.

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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Pfam Clan

This family is a member of clan GCS (CL0286), which has the following description:

This clan represents a superfamily of carboxylate-amine/ammonia ligases [1] that includes Gamma-Glutamylcysteine synthetase (gamma-GCS) and glutamine synthetase (GS). Gamma-Glutamylcysteine synthetase (gamma-GCS) catalyses the first step in the de novo biosynthesis of glutathione.

The clan contains the following 9 members:

Amidoligase_2 ATP-gua_Ptrans COOH-NH2_lig DUF2126 GCS GCS2 Gln-synt_C Glu_cys_ligase Pup_ligase

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...

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
(2189)
Representative proteomes NCBI
(1830)
Meta
(1695)
RP15
(201)
RP35
(465)
RP55
(597)
RP75
(681)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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

Format an alignment

  Seed
(12)
Full
(2189)
Representative proteomes NCBI
(1830)
Meta
(1695)
RP15
(201)
RP35
(465)
RP55
(597)
RP75
(681)
Alignment:
Format:
Order:
Sequence:
Gaps:
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
(2189)
Representative proteomes NCBI
(1830)
Meta
(1695)
RP15
(201)
RP35
(465)
RP55
(597)
RP75
(681)
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.

Pfam alignments:

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: COG2170
Previous IDs: none
Type: Family
Author: Kerrison ND, Finn RD
Number in seed: 12
Number in full: 2189
Average length of the domain: 275.90 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 68.31 %

HMM information View help on HMM parameters

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 20.0 20.0
Trusted cut-off 20.0 20.0
Noise cut-off 19.9 19.9
Model length: 288
Family (HMM) version: 8
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...

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Tree controls

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Interactions

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

GCS2

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 GCS2 domain has been found. There are 13 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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