Summary: Prokaryotic glutathione synthetase, ATP-grasp 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 synthetase". 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 email@example.com and we will try to help.
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.
Glutathione synthetase Edit Wikipedia article
|Locus||Chr. 20 q11.2|
|Eukaryotic glutathione synthase|
Human glutathione synthetase
|Eukaryotic glutathione synthase, ATP binding domain|
Human glutathione synthetase
|Prokaryotic glutathione synthetase, N-terminal domain|
Structure of escherichia coli glutathione synthetase at ph 7.5
|Prokaryotic glutathione synthetase, ATP-grasp domain|
Structure of escherichia coli glutathione synthetase at ph 7.5
Glutathione synthetase (GSS) (EC 220.127.116.11) is the second enzyme in the glutathione (GSH) biosynthesis pathway. It catalyses the condensation of gamma-glutamylcysteine and glycine, to form glutathione. Glutathione synthetase is also a potent antioxidant. It is found in a large number of species including bacteria, yeast, mammals, and plants.
In humans, defects in GSS are inherited in an autosomal recessive way and are the cause of severe metabolic acidosis, 5-oxoprolinuria, increased rate of haemolysis, and defective function of the central nervous system. Deficiencies in GSS can cause a spectrum of deleterious symptoms in plants and human beings alike.
In eukaryotes, this is a homodimeric enzyme. The substrate-binding domain has a 3-layer alpha/beta/alpha structure. This enzyme utilizes and stabilizes an acylphosphate intermediate to later perform a favorable nucleophilic attack of glycine.
Human and yeast glutathione synthetases are homodimers, meaning they are composed of two identical subunits of itself non-covalently bound to each other. On the other hand, E. coli glutathione synthetase is a homotetramer. Nevertheless, they are part of the ATP-grasp superfamily, which consists of 21 enzymes that contain an ATP-grasp fold. Each subunit interacts with each other through alpha helix and beta sheet hydrogen bonding interactions and contains two domains. One domain facilitates the ATP-grasp mechanism and the other is the catalytic active site for γ-glutamylcysteine. The ATP-grasp fold is conserved within the ATP-grasp superfamily and is characterized by two alpha helices and beta sheets that hold onto the ATP molecule between them. The domain containing the active site exhibits interesting properties of specificity. In contrast to γ-glutamylcysteine synthetase, glutathione synthetase accepts a large variety of glutamyl-modified analogs of γ-glutamylcysteine, but is much more specific for cysteine-modified analogs of γ-glutamylcysteine. Crystalline structures have shown glutathione synthetase bound to GSH, ADP, two magnesium ions, and a sulfate ion. Two magnesium ions function to stabilize the acylphosphate intermediate, facilitate binding of ATP, and activate removal of phosphate group from ATP. Sulfate ion serves as a replacement for inorganic phosphate once the acylphosphate intermediate is formed inside the active site.
The biosynthetic mechanisms for synthetases use energy from nucleoside triphosphates, whereas synthases do not. Glutathione synthetase stays true to this rule, in that it uses the energy generated by ATP. Initially, the carboxylate group on γ-glutamylcysteine is converted into an acyl phosphate by the transfer of an inorganic phosphate group of ATP to generate an acyl phosphate intermediate. Then the amino group of glycine participates in a nucleophilic attack, displacing the phosphate group and forming GSH. After the final GSH product is made, it can be used by glutathione peroxidase to neutralize reactive oxygen species (ROS) such as H2O2 or Glutathione S-transferases in the detoxification of xenobiotics.
Glutathione synthetase is important for a variety of biological functions in multiple organisms. In Arabidopsis thaliana, low levels of glutathione synthetase have resulted in increased vulnerability to stressors such as heavy metals, toxic organic chemicals, and oxidative stress. The presence of a thiol functional group allows its product GSH to serve both as an effective oxidizing and reducing agent in numerous biological scenarios. Thiols can easily accept a pair of electrons and become oxidized to disulfides, and the disulfides can be readily reduced to regenerate thiols. Additionally, the thiol side chain of cysteines serve as potent nucleophiles and react with oxidants and electrophilic species that would otherwise cause damage to the cell. Interactions with certain metals also stabilize thiolate intermediates.
In humans, glutathione synthetase functions in a similar manner. Its product GSH participates in cellular pathways involved in homeostasis and cellular maintenance. For instance, glutathione peroxidases catalyze the oxidation of GSH to glutathione disulfide (GSSG) by reducing free radicals and reactive oxygen species such as hydrogen peroxide. Glutathione S-transferase uses GSH to clean up various metabolites, xenobiotics, and electrophiles to mercapturates for excretion. Because of its antioxidant role, GSS mostly produce GSH inside the cytoplasm of liver cells and imported to mitochondria where detoxification occurs.]] GSH is also essential for the activation of the immune system to generate robust defense mechanisms against invading pathogens. GSH is capable of preventing infection from the influenza virus.
Patients with mutations in the GSS gene develop glutathione synthetase (GSS) deficiency, an autosomal recessive disorder. Patients develop a wide range of symptoms depending on the severity of the mutations. Mildly affected patients experience a compensated haemolytic anaemia because mutations affect stability of the enzyme. Moderately and severely affected individuals have enzymes with dysfunctional catalytic sites, rendering it unable to participate in detoxification reactions. Physiological symptoms include metabolic acidosis, neurological defects, and increased susceptibility to pathogenic infections.
Treatment of individuals with glutathione synthetase deficiency generally involve therapeutic treatments to address mild to severe symptoms and conditions. In order to treat metabolic acidosis, severely affected patients are given large amounts of bicarbonate and antioxidants such as vitamin E and vitamin C. In mild cases, ascorbate and N-acetylcysteine have been shown to increase glutathione levels and increase erythrocyte production. It is important to note that because glutathione synthetase deficiency is so rare, it is poorly understood. The disease also appears on a spectrum, so it is even more difficult to generalize among the few cases that occur.
- Gogos A, Shapiro L (Dec 2002). "Large conformational changes in the catalytic cycle of glutathione synthase". Structure. 10 (12): 1669–76. doi:10.1016/S0969-2126(02)00906-1. PMID 12467574.
- Njålsson R, Norgren S (2005). "Physiological and pathological aspects of GSH metabolism.". Acta Paediatr. 94 (2): 132–7. doi:10.1080/08035250410025285. PMID 15981742.
- Li H, Xu H, Graham DE, White RH (Aug 2003). "Glutathione synthetase homologs encode alpha-L-glutamate ligases for methanogenic coenzyme F420 and tetrahydrosarcinapterin biosyntheses". Proceedings of the National Academy of Sciences of the United States of America. 100 (17): 9785–90. doi:10.1073/pnas.1733391100. PMC . PMID 12909715.
- Njålsson R (Sep 2005). "Glutathione synthetase deficiency". Cellular and Molecular Life Sciences. 62 (17): 1938–45. doi:10.1007/s00018-005-5163-7. PMID 15990954.
- O'Neill M. "Glutathione Synthetase Deficiency". Online Mendelian Inheritance in Man.
- Polekhina G, Board PG, Gali RR, Rossjohn J, Parker MW (Jun 1999). "Molecular basis of glutathione synthetase deficiency and a rare gene permutation event". The EMBO Journal. 18 (12): 3204–13. doi:10.1093/emboj/18.12.3204. PMC . PMID 10369661.
- Banerjee R (2007). "Antioxidant Molecules and Redox Factors". Redox Biochemistry. Hoboken, N.J.: Wiley. p. 16. ISBN 978-0-471-78624-5.
- Fawaz MV, Topper ME, Firestine SM (Dec 2011). "The ATP-grasp enzymes". Bioorganic Chemistry. 39 (5-6): 185–91. doi:10.1016/j.bioorg.2011.08.004. PMC . PMID 21920581.
- Fyfe PK, Alphey MS, Hunter WN (Apr 2010). "Structure of Trypanosoma brucei glutathione synthetase: domain and loop alterations in the catalytic cycle of a highly conserved enzyme". Molecular and Biochemical Parasitology. 170 (2): 93–9. doi:10.1016/j.molbiopara.2009.12.011. PMC . PMID 20045436.
- Galperin MY, Koonin EV (1997). "A diverse superfamily of enzymes with ATP-dependent carboxylate-amine/thiol ligase activity". Protein Science : a Publication of the Protein Society. 6 (12): 2639–43. doi:10.1002/pro.5560061218. PMC . PMID 9416615.
- Meister A (1978). "Current Status of the γ-Glutamyl Cycle". In Wendel A, Sies H. Functions of Glutathione in Liver and Kidney. Berlin, Heidelberg: Springer Berlin Heidelberg. p. 49. ISBN 978-3-642-67132-6.
- Hara T, Kato H, Katsube Y, Oda J (Sep 1996). "A pseudo-michaelis quaternary complex in the reverse reaction of a ligase: structure of Escherichia coli B glutathione synthetase complexed with ADP, glutathione, and sulfate at 2.0 A resolution". Biochemistry. 35 (37): 11967–74. doi:10.1021/bi9605245. PMID 8810901.
- "Synthases and Ligases". IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN), and Nomenclature Commission of IUB (NC-IUB), Newsletter. 1984.
- Herrera K, Cahoon RE, Kumaran S, Jez J (Jun 2007). "Reaction mechanism of glutathione synthetase from Arabidopsis thaliana: site-directed mutagenesis of active site residues". The Journal of Biological Chemistry. 282 (23): 17157–65. doi:10.1074/jbc.M700804200. PMID 17452339.
- Moyer AM, Sun Z, Batzler AJ, Li L, Schaid DJ, Yang P, Weinshilboum RM (Mar 2010). "Glutathione pathway genetic polymorphisms and lung cancer survival after platinum-based chemotherapy". Cancer Epidemiology, Biomarkers & Prevention. 19 (3): 811–21. doi:10.1158/1055-9965.EPI-09-0871. PMC . PMID 20200426.
- Xiang C, Werner BL, Christensen EM, Oliver DJ (Jun 2001). "The biological functions of glutathione revisited in arabidopsis transgenic plants with altered glutathione levels". Plant Physiology. 126 (2): 564–74. doi:10.1104/pp.126.2.564. PMC . PMID 11402187.
- Conte ML, Carroll KS (14 February 2013). "The Chemistry of Thiol Oxidation and Detection" (PDF). Oxidative Stress and Redox Regulation. pp. 1–42. doi:10.1007/978-94-007-5787-5_1.
- Suzuki N, Higuchi T, Nagano T (Aug 2002). "Multiple active intermediates in oxidation reaction catalyzed by synthetic heme-thiolate complex relevant to cytochrome p450". Journal of the American Chemical Society. 124 (32): 9622–8. doi:10.1021/ja0115013. PMID 12167058.
- Fang YZ, Yang S, Wu G (Oct 2002). "Free radicals, antioxidants, and nutrition". Nutrition. 18 (10): 872–9. doi:10.1016/S0899-9007(02)00916-4. PMID 12361782.
- Ribas V, García-Ruiz C, Fernández-Checa JC (Jul 2014). "Glutathione and mitochondria". Frontiers in Pharmacology. 5: 151. doi:10.3389/fphar.2014.00151. PMC . PMID 25024695.
- Townsend DM, Tew KD, Tapiero H (2003). "The importance of glutathione in human disease". Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie. 57 (3-4): 145–55. doi:10.1016/S0753-3322(03)00043-X. PMID 12818476.
- Cai J, Chen Y, Seth S, Furukawa S, Compans RW, Jones DP (Apr 2003). "Inhibition of influenza infection by glutathione". Free Radical Biology & Medicine. 34 (7): 928–36. doi:10.1016/S0891-5849(03)00023-6. PMID 12654482.
- Ristoff E, Mayatepek E, Larsson A (Jul 2001). "Long-term clinical outcome in patients with glutathione synthetase deficiency". The Journal of Pediatrics. 139 (1): 79–84. doi:10.1067/mpd.2001.114480. PMID 11445798.
- Kraut JA, Madias NE (May 2010). "Metabolic acidosis: pathophysiology, diagnosis and management". Nature Reviews. Nephrology. 6 (5): 274–85. doi:10.1038/nrneph.2010.33. PMID 20308999.
- Jain A, Buist NR, Kennaway NG, Powell BR, Auld PA, Mårtensson J (Feb 1994). "Effect of ascorbate or N-acetylcysteine treatment in a patient with hereditary glutathione synthetase deficiency". The Journal of Pediatrics. 124 (2): 229–33. doi:10.1016/S0022-3476(94)70309-4. PMID 8301428.
- Ristoff E, Larsson A (2007). "Inborn errors in the metabolism of glutathione". Orphanet Journal of Rare Diseases. 2: 16. doi:10.1186/1750-1172-2-16. PMC . PMID 17397529.
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.
Prokaryotic glutathione synthetase, ATP-grasp domain Provide feedback
No Pfam abstract.
Yamaguchi H, Kato H, Hata Y, Nishioka T, Kimura A, Oda J, Katsube Y; , J Mol Biol 1993;229:1083-1100.: Three-dimensional structure of the glutathione synthetase from Escherichia coli B at 2.0 A resolution. PUBMED:8445637 EPMC:8445637
Internal database links
|SCOOP:||ATP-grasp ATP-grasp_2 ATP-grasp_3 ATP-grasp_4 ATP-grasp_5 ATPgrasp_ST ATPgrasp_Ter ATPgrasp_YheCD CPSase_L_D2 Dala_Dala_lig_C DUF4343 GARS_A RimK Synapsin_C|
|Similarity to PfamA using HHSearch:||ATP-grasp_3 RimK ATPgrasp_ST ATPgrasp_YheCD|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR004218Prokaryotic glutathione synthetase EC (glutathione synthase) catalyses the conversion of gamma-L-glutamyl-L-cysteine and glycine to orthophosphate and glutathione in the presence of ATP. This is the second step in glutathione biosynthesis. The enzyme is inhibited by 7,8-dihydrofolate, methotrexate and trimethoprim. This is the ATP-binding domain of the enzyme.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||ATP binding (GO:0005524)|
|glutathione synthase activity (GO:0004363)|
|Biological process||glutathione biosynthetic process (GO:0006750)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- a link to the page in the Pfam site showing information about the sequence that the graphic describes
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Note that you can see the family page for a particular domain by clicking on the graphic. You can also choose to see all sequences which have a given architecture by clicking on the Show link in each row.
Finally, because some families can be found in a very large number of architectures, we load only the first fifty architectures by default. If you want to see more architectures, click the button at the bottom of the page to load the next set.
Loading domain graphics...
The ATP-grasp domain is found in a wide variety of carboxylate-amine/thiol ligases . It is composed of two subdomains, with ATP being bound in the cleft between the two.
The clan contains the following 22 members:ATP-grasp ATP-grasp_2 ATP-grasp_3 ATP-grasp_4 ATP-grasp_5 ATPgrasp_ST ATPgrasp_Ter ATPgrasp_TupA ATPgrasp_YheCD CP_ATPgrasp_1 CP_ATPgrasp_2 CPSase_L_D2 Dala_Dala_lig_C DUF1297 GARS_A GSH-S_ATP GSP_synth Ins134_P3_kin PPDK_N RimK Synapsin_C TTL
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.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the UniProtKB sequence database using the family HMM
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- a Java applet developed at the University of Dundee. You will need Java installed before running jalview
- 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
- 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.
You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
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.
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.
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.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
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.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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...
If you find these logos useful in your own work, please consider citing the following article:
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.
|Seed source:||Structural domain|
|Author:||Griffiths-Jones SR, Bateman A|
|Number in seed:||32|
|Number in full:||1754|
|Average length of the domain:||169.40 aa|
|Average identity of full alignment:||41 %|
|Average coverage of the sequence by the domain:||51.76 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||15|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the 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:
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".
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.
The tree shows the occurrence of this domain across different species. More...
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.
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
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.
There is 1 interaction for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
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 GSH-S_ATP domain has been found. There are 4 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.
Loading structure mapping...