Summary: Glutamine synthetase, catalytic 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 "Glutamine 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.
Glutamine synthetase Edit Wikipedia article
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / QuickGO|
|SCOPe||2gls / SUPFAM|
|SCOPe||2gls / SUPFAM|
|glutamate-ammonia ligase (glutamine synthetase)|
|Locus||Chr. 1 q31|
Glutamine Synthetase uses ammonia produced by nitrate reduction, amino acid degradation, and photorespiration. The amide group of glutamate is a nitrogen source for the synthesis of glutamine pathway metabolites.
Other reactions may take place via GS. Competition between ammonium ion and water, their binding affinities, and the concentration of ammonium ion, influences glutamine synthesis and glutamine hydrolysis. Glutamine is formed if an ammonium ion attacks the acyl-phosphate intermediate, while glutamate is remade if water attacks the intermediate. Ammonium ion binds more strongly than water to GS due to electrostatic forces between a cation and a negatively charged pocket. Another possible reaction is upon NH2OH binding to GS, rather than NH4+, yields Î³-glutamylhydroxamate.
Glutamine Synthetase can be composed of 8, 10, or 12 identical subunits separated into two face-to-face rings. Bacterial GS are dodecamers with 12 active sites between each monomer. Each active site creates a â€˜tunnelâ€™ which is the site of three distinct substrate binding sites: nucleotide, ammonium ion, and amino acid. ATP binds to the top of the bifunnel that opens to the external surface of GS. Glutamate binds at the bottom of the active site. The middle of the bifunnel contains two sites in which divalent cations bind (Mn+2 or Mg+2). One cation binding site is involved in phosphoryl transfer of ATP to glutamate, while the second stabilizes active GS and helps with the binding of glutamate.
Hydrogen bonding and hydrophobic interactions hold the two rings of GS together. Each subunit possesses a C-terminus and an N-terminus in its sequence. The C-terminus (helical thong) stabilizes the GS structure by inserting into the hydrophobic region of the subunit across in the other ring. The N-terminus is exposed to the solvent. In addition, the central channel is formed via six four-stranded Î²-sheets composed of anti-parallel loops from the twelve subunits.
GS catalyzes the ATP-dependent condensation of glutamate with ammonia to yield glutamine. The hydrolysis of ATP drives the first step of a two-part, concerted mechanism. ATP phosphorylates glutamate to form ADP and an acyl-phosphate intermediate, Î³-glutamyl phosphate, which reacts with ammonia, forming glutamine and inorganic phosphate. ADP and Pi do not dissociate until ammonia binds and glutamine is released.
ATP binds first to the top of the active site near a cation binding site, while glutamate binds near the second cation binding site at the bottom of the active site. The presence of ADP causes a conformational shift in GS that stabilizes the Î³-glutamyl phosphate moiety. Ammonium binds strongly to GS only if the acyl-phosphate intermediate is present. Ammonium, rather than ammonia, binds to GS because the binding site is polar and exposed to solvent. In the second step, deprotonation of ammonium allows ammonia to attack the intermediate from its nearby site to form glutamine. Phosphate leaves through the top of the active site, while glutamine leaves through the bottom (between two rings).Goodsell, DS (June 2002). "Glutamine Synthetase". RCSB Protein Data Bank. Retrieved 8 May 2010.
GS is present predominantly in the brain, kidneys, and liver. GS in the brain participates in the metabolic regulation of glutamate, the detoxification of brain ammonia, the assimilation of ammonia, recyclization of neurotransmitters, and termination of neurotransmitter signals. GS, in the brain, is found primarily in astrocytes. Astrocytes protect neurons against excitotoxicity by taking up excess ammonia and glutamate. In hyperammonemic environments (high levels of ammonia), astroglial swelling occurs. Different perspectives have approached the problem of astroglial swelling. One study shows that morphological changes occur that increase GS expression in glutamatergic areas or other adaptations that alleviates high levels of glutamate and ammonia. Another perspective is that astrocyte swelling is due to glutamine accumulation. To prevent increased levels of cortical glutamate and cortical water content, a study has been conducted to prevent GS activity in rats by the use of MSO.
- Class I enzymes (GSI) are specific to prokaryotes, and are oligomers of 12 identical subunits. The activity of GSI-type enzyme is controlled by the adenylation of a tyrosine residue. The adenylated enzyme is inactive.
- Class II enzymes (GSII) are found in eukaryotes and in bacteria belonging to the Rhizobiaceae, Frankiaceae, and Streptomycetaceae families (these bacteria have also a class-I GS). GSII are decamer of identical subunits..
Plants have two or more isozymes of GSII, one of the isozymes is translocated into the chloroplast. Another form is cytosolic. The cytosolic GS gene translation is regulated by its 5' untranslated region (UTR), while its 3' UTR plays role in transcript turnover.
- Class III enzymes (GSIII) have, currently, only been found in Bacteroides fragilis and in Butyrivibrio fibrisolvens. It is a double-ringed dodecamer of identical chains. It is much larger (about 700 amino acids) than the GSI (450 to 470 amino acids) or GSII (350 to 420 amino acids) enzymes.
While the three classes of GSs are clearly structurally related, the sequence similarities are not so extensive.
Regulation and inhibition
Regulation of GS only occurs in prokaryotes. GS is subject to reversible covalent modification. Tyr397 of all 12 subunits can undergo adenylylation or deadenylylation by adenylyl transferase (AT), a bifunctional regulatory enzyme. Adenylylation is a post-translational modification involving the covalent attachment of AMP to a protein side chain. Each adenylylation requires an ATP and complete inhibition of GS requires 12 ATP. Deadenylylation by AT involves phosphorolytic removal of the Tyr-linked adenylyl groups as ADP. AT activity is influenced by the regulatory protein that is associated with it: PII, a 44-kD trimer. PII also undergoes post-translational modification by uridylyl transferase, thus PII has two forms. The state of PII dictates the activity of adenylyl transferase. If PII is not uridylylated, then it will take on the PIIA form. The AT:PIIA complex will deactivate GS by adenylylation. If PII is uridylylated, then it will take on the PIID form. The AT:PIID complex will activate GS by deadenylylation. The AT:PIIA and AT:PIID complexes are allosterically regulated in a reciprocal fashion by Î±-ketoglutarate (Î±-KG) and glutamine (Gln). Gln will activate AT:PIIA activity and inhibits AT:PIID, leading to adenylylation and subsequent deactivation of GS. Furthermore, Gln favors the conversion of PIID to PIIA. The effects of Î±-KG on the complexes are opposite. In the majority of gram-negative bacteria, GS can be modified by adenylylation (some cyanobacteria and green algae or exceptions).
Inhibition of GS has largely focused on amino site ligands. Other inhibitors are the result of glutamine metabolism: tryptophan, histidine, carbamoyl phosphate, glucosamine-6-phosphate, cytidine triphosphate (CTP), and adenosine monophosphate (AMP). Other inhibitors/regulators are glycine and alanine. Alanine, glycine, and serine bind to the glutamate substrate site. GDP, AMP, ADP bind to the ATP site. L-serine, L-alanine, and glycine bind to the site for L-glutamate in unadenylated GS. The four amino acids bind to the site by their common atoms, â€œthe main chainâ€ of amino acids. Glutamate is another product of glutamine metabolism; however, glutamate is a substrate for GS inhibiting it to act as a regulator to GS.2 Each inhibitor can reduce the activity of the enzyme; once all final glutamine metabolites are bound to GS, the activity of GS is almost completely inhibited. Many inhibitory input signals allows for fine tuning of GS by reflecting nitrogen levels in the organism.
Feedback regulation distinguishes the difference between two eukaryotic types of GS: brain and non-brain tissues. Non-brain GS responds to end-product feedback inhibition, while brain GS does not. High concentrations of glutamine-dependent metabolites should inhibit GS activity, while low concentrations should activate GS activity.
- Methionine sulfoximine (MSO): MSO is an inhibitor that binds to the glutamate site. Bound to GS, MSO is phosphorylated by ATP that results in an irreversible, non-covalent inhibition of GS. The S-isomer configuration is more inhibitory. Glutamate entry is blocked into the active site by a stabilization of the flexible loop in the active site by MSO.
- Phosphinothricin(PPT, Glufosinate): Phosphinothricin is an inhibitor that binds to the glutamate site. Glufosinate is used as an herbicide. Glufosinate treated plants die due to a buildup of ammonia and a cessation of photosynthesis.
- Many synthetic inhibitors are available today.
Research on E. coli revealed that GS is regulated through gene expression. The gene that encodes the GS subunit is designated glnA. Transcription of glnA is dependent on NRI (a specific transcriptional enhancer). Active transcription occurs if NRI is in its phosphorylated form, designated NRI-P. Phosphorylation of NRI is catalyzed by NRII, a protein kinase. If NRII is complexed with PIIA then it will function as a phosphatase and NRI-P is converted back to NRI. In this case, transcription of glnA ceases.
GS is subject to completely different regulatory mechanisms in cyanobacteria. Instead of the common NtrC-NtrB two component system, cyanobacteria harbour the transcriptional regulator NtcA which is restricted to this clade and controls expression of GS and a multitude of genes involved in Nitrogen metabolism. Moreover, GS in Cyanobacteria is not covalently modified to raise sensitivity for feedback inhibition. Instead, GS in Cyanobacteria is inhibited by small proteins, termed GS inactivating factors (IFs) whose transcription is negatively regulated by NtcA. These inactivating factors are furthermore regulated by different Non-coding RNAs: The sRNA NsiR4 interacts with the 5'UTR of the mRNA of the GS inactivating factor IF7 (gifA mRNA) and reduces its expression. NsiR4 expression is under positive control of the nitrogen control transcription factor NtcA. In addition, expression of the GS inactivating factor IF17 is controlled by a glutamine-binding riboswitch.
- doi:10.1021/bi002438h. PMID 11329256. ; Gill HS, Eisenberg D (February 2001). "The crystal structure of phosphinothricin in the active site of glutamine synthetase illuminates the mechanism of enzymatic inhibition". Biochemistry. 40 (7): 1903â€“12.
- PMID 2572586. ; Yamashita MM, Almassy RJ, Janson CA, Cascio D, Eisenberg D (October 1989). "Refined atomic model of glutamine synthetase at 3.5 A resolution". J. Biol. Chem. 264 (30): 17681â€“90.
- Eisenberg D, Almassy RJ, Janson CA, Chapman MS, Suh SW, Cascio D, Smith WW (1987). "Some evolutionary relationships of the primary biological catalysts glutamine synthetase and RuBisCO". Cold Spring Harb. Symp. Quant. Biol. 52: 483â€“90. doi:10.1101/sqb.1987.052.01.055. PMID 2900091.
- Liaw SH, Kuo I, Eisenberg D (Nov 1995). "Discovery of the ammonium substrate site on glutamine synthetase, a third cation binding site". Protein Sci. 4 (11): 2358â€“65. doi:10.1002/pro.5560041114. PMC 2143006. PMID 8563633.
- Liaw SH, Pan C, Eisenberg D (Jun 1993). "Feedback inhibition of fully unadenylylated glutamine synthetase from Salmonella typhimurium by glycine, alanine, and serine". Proc. Natl. Acad. Sci. USA. 90 (11): 4996â€“5000. doi:10.1073/pnas.90.11.4996. PMC 46640. PMID 8099447.
- Eisenberg D, Gill HS, Pfluegl GM, Rotstein SH (Mar 2000). "Structure-function relationships of glutamine synthetases". Biochim Biophys Acta. 1477 (1â€“2): 122â€“45. doi:10.1016/S0167-4838(99)00270-8. PMID 10708854.
- Liaw SH, Eisenberg D (Jan 1994). "Structural model for the reaction mechanism of glutamine synthetase, based on five crystal structures of enzyme-substrate complexes". Biochemistry. 33 (3): 675â€“81. doi:10.1021/bi00169a007. PMID 7904828.
- Stryer L, Berg JM, Tymoczko JL (2007). Biochemistry (6th ed.). San Francisco: W.H. Freeman. pp. 679â€“706. ISBN 978-0-7167-8724-2.
- Goodsell DS (June 2002). "Glutamine Synthetase". Molecule of the month. RCSB Protein Data Bank. Retrieved 2010-05-08.
- Krajewski WW, Collins R, Holmberg-Schiavone L, Jones TA, Karlberg T, Mowbray SL (Jan 2008). "Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design". J Mol Biol. 375 (1): 317â€“28. doi:10.1016/j.jmb.2007.10.029. PMID 18005987.
- Ginsburg A, Yeh J, Hennig SB, Denton MD (Feb 1970). "Some effects of adenylylation on the biosynthetic properties of the glutamine synthetase from Escherichia coli". Biochemistry. 9 (3): 633â€“49. doi:10.1021/bi00805a025. PMID 4906326.
- Hunt JB, Smyrniotis PZ, Ginsburg A, Stadtman ER (Jan 1975). "Metal ion requirement by glutamine synthetase of Escherichia coli in catalysis of gamma-glutamyl transfer". Arch Biochem Biophys. 166 (1): 102â€“24. doi:10.1016/0003-9861(75)90370-7. PMID 235885.
- Suarez I, Bodega G, Fernandez B (Augâ€“Sep 2002). "Glutamine synthetase in brain: effect of ammonia". Neurochem. Int. 41 (2â€“3): 123â€“42. doi:10.1016/S0197-0186(02)00033-5. PMID 12020613.
- Venkatesh K, Srikanth L, Vengamma B, Chandrasekhar C, Sanjeevkumar A, Mouleshwara Prasad BC, Sarma PV. In vitro differentiation of cultured human CD34+ cells into astrocytes. Neurol India 2013;61:383-8
- Willard-Mack CL, Koehler RC, Hirata T, et al. (March 1996). "Inhibition of glutamine synthetase reduces ammonia-induced astrocyte swelling in rat". Neuroscience. 71 (2): 589â€“99. doi:10.1016/0306-4522(95)00462-9. PMID 9053810.
- Tanigami H, Rebel A, Martin LJ, Chen TY, Brusilow SW, Traystman RJ, Koehler RC (2005). "Effect of glutamine synthetase inhibition on astrocyte swelling and altered astroglial protein expression during hyperammonemia in rats". Neuroscience. 131 (2): 437â€“49. doi:10.1016/j.neuroscience.2004.10.045. PMC 1819407. PMID 15708485.
- Kumada Y, Benson DR, Hillemann D, Hosted TJ, Rochefort DA, Thompson CJ, Wohlleben W, Tateno Y (April 1993). "Evolution of the glutamine synthetase gene, one of the oldest existing and functioning genes". Proc. Natl. Acad. Sci. U.S.A. 90 (7): 3009â€“13. doi:10.1073/pnas.90.7.3009. PMC 46226. PMID 8096645.
- Shatters RG, Kahn ML (November 1989). "Glutamine synthetase II in Rhizobium: reexamination of the proposed horizontal transfer of DNA from eukaryotes to prokaryotes". J. Mol. Evol. 29 (5): 422â€“8. doi:10.1007/BF02602912. PMID 2575672.
- Brown JR, Masuchi Y, Robb FT, Doolittle WF (June 1994). "Evolutionary relationships of bacterial and archaeal glutamine synthetase genes". J. Mol. Evol. 38 (6): 566â€“76. doi:10.1007/BF00175876. PMID 7916055.
- "GSI structure". Archived from the original on 2008-12-17. Retrieved 2009-03-31.
- InterPro:IPR001637 Glutamine synthetase class-I, adenylation site
- Ortega JL, Wilson OL, Sengupta-Gopalan C (December 2012). "The 5' untranslated region of the soybean cytosolic glutamine synthetase Î²(1) gene contains prokaryotic translation initiation signals and acts as a translational enhancer in plants". Molecular Genetics and Genomics. 287 (11â€“12): 881â€“93. doi:10.1007/s00438-012-0724-6. PMC 3881598. PMID 23080263.
- van Rooyen JM, Abratt VR, Sewell BT (August 2006). "Three-dimensional structure of a type III glutamine synthetase by single-particle reconstruction". J. Mol. Biol. 361 (4): 796â€“810. doi:10.1016/j.jmb.2006.06.026. hdl:11394/1617. PMID 16879836.
- Garrett, Grisham (2017). Biochemistry (6th Edition). United States of America: Cengage Learning. pp. 886â€“889. ISBN 978-1-305-57720-6.
- Ivanovsky RN, Khatipov EA (1994). "Evidence of covalent modification of glutamine synthetase in the purple sulfur bacterium". FEMS Microbiology Letters. 122 (1â€“2): 115â€“119. doi:10.1111/j.1574-6968.1994.tb07153.x.
- Krishnan IS, Singhal RK, Dua RD (Apr 1986). "Purification and characterization of glutamine synthetase from Clostridium pasteurianum". Biochemistry. 25 (7): 1589â€“99. doi:10.1021/bi00355a021. PMID 2871863.
- Bolay, Paul; Muro-Pastor, M.; Florencio, Francisco; KlÃ¤hn, Stephan (27 October 2018). "The Distinctive Regulation of Cyanobacterial Glutamine Synthetase". Life. 8 (4): 52. doi:10.3390/life8040052.
- Merrick MJ, Edwards RA (December 1995). "Nitrogen control in bacteria". Microbiological Reviews. 59 (4): 604â€“22. PMID 8531888.
- Fisher R, Tuli R, Haselkorn R (June 1981). "A cloned cyanobacterial gene for glutamine synthetase functions in Escherichia coli, but the enzyme is not adenylylated". Proceedings of the National Academy of Sciences of the United States of America. 78 (6): 3393â€“7. doi:10.1073/pnas.78.6.3393. PMC 319574. PMID 6115380.
- Vega-Palas MA, Flores E, Herrero A (July 1992). "NtcA, a global nitrogen regulator from the cyanobacterium Synechococcus that belongs to the Crp family of bacterial regulators". Molecular Microbiology. 6 (13): 1853â€“9. doi:10.1111/j.1365-2958.1992.tb01357.x. PMID 1630321.
- Reyes JC, Muro-Pastor MI, Florencio FJ (April 1997). "Transcription of glutamine synthetase genes (glnA and glnN) from the cyanobacterium Synechocystis sp. strain PCC 6803 is differently regulated in response to nitrogen availability". Journal of Bacteriology. 179 (8): 2678â€“89. doi:10.1128/jb.179.8.2678-2689.1997. PMC 179018. PMID 9098067.
- GarcÃa-DomÃnguez M, Reyes JC, Florencio FJ (June 1999). "Glutamine synthetase inactivation by protein-protein interaction". Proceedings of the National Academy of Sciences of the United States of America. 96 (13): 7161â€“6. doi:10.1073/pnas.96.13.7161. PMC 22038. PMID 10377385.
- GarcÃa-DomÃnguez M, Reyes JC, Florencio FJ (March 2000). "NtcA represses transcription of gifA and gifB, genes that encode inhibitors of glutamine synthetase type I from Synechocystis sp. PCC 6803". Molecular Microbiology. 35 (5): 1192â€“201. doi:10.1046/j.1365-2958.2000.01789.x. PMID 10712699.
- KlÃ¤hn S, Schaal C, Georg J, Baumgartner D, Knippen G, Hagemann M, Muro-Pastor AM, Hess WR (November 2015). "The sRNA NsiR4 is involved in nitrogen assimilation control in cyanobacteria by targeting glutamine synthetase inactivating factor IF7". Proceedings of the National Academy of Sciences of the United States of America. 112 (45): E6243â€“52. doi:10.1073/pnas.1508412112. PMC 4653137. PMID 26494284.
- KlÃ¤hn S, Bolay P, Wright PR, Atilho RM, Brewer KI, Hagemann M, Breaker RR, Hess WR (August 2018). "A glutamine riboswitch is a key element for the regulation of glutamine synthetase in cyanobacteria". Nucleic Acids Research. doi:10.1093/nar/gky709. PMID 30085248.
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.
Glutamine synthetase, catalytic domain Provide feedback
No Pfam abstract.
Internal database links
|Similarity to PfamA using HHSearch:||GCS2|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR008146
- Class I enzymes (GSI) are specific to prokaryotes, and are oligomers of 12 identical subunits. The activity of GSI-type enzyme is controlled by the adenylation of a tyrosine residue. The adenylated enzyme is inactive (see INTERPRO).
- Class II enzymes (GSII) are found in eukaryotes and in bacteria belonging to the Rhizobiaceae, Frankiaceae, and Streptomycetaceae families (these bacteria have also a class-I GS). GSII are octamer of identical subunits. Plants have two or more isozymes of GSII, one of the isozymes is translocated into the chloroplast.
- Class III enzymes (GSIII) have been found in Bacteroides fragilis. in Butyrivibrio fibrisolvens. It is a hexamer of identical chains and in some protozoa. It is much larger (about 700 amino acids) than the GSI (450 to 470 amino acids) or GSII (350 to 420 amino acids) enzymes.
While the three classes of GS's are clearly structurally related, the sequence similarities are not so extensive.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||glutamate-ammonia ligase activity (GO:0004356)|
|Biological process||nitrogen compound metabolic process (GO:0006807)|
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...
This clan represents a superfamily of carboxylate-amine/ammonia ligases  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 DUF2126 GatB_N GCS GCS2 Gln-synt_C Glu_cys_ligase Pup_ligase
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.
|Author:||Sonnhammer ELL , Griffiths-Jones SR , Eberhardt R|
|Number in seed:||69|
|Number in full:||20560|
|Average length of the domain:||304.50 aa|
|Average identity of full alignment:||27 %|
|Average coverage of the sequence by the domain:||64.30 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||24|
|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 are 5 interactions 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 Gln-synt_C domain has been found. There are 392 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.
Loading structure mapping...