Summary: Aminomethyltransferase folate-binding 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 "Glycine cleavage system". 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 firstname.lastname@example.org 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.
Glycine cleavage system Edit Wikipedia article
|Glycine cleavage H-protein|
refined structures at 2 angstroms and 2.2 angstroms of the two forms of the h-protein, a lipoamide-containing protein of the glycine decarboxylase
|Glycine cleavage T-protein, Aminomethyltransferase folate-binding domain|
crystal structure of a component of glycine cleavage system: t-protein from pyrococcus horikoshii ot3 at 1.5 a resolution
|Glycine cleavage T-protein C-terminal barrel domain|
crystal structure of t-protein of the glycine cleavage system
The glycine cleavage system (GCS) is also known as the glycine decarboxylase complex or GDC. The system is a series of enzymes that are triggered in response to high concentrations of the amino acid glycine. The same set of enzymes is sometimes referred to as glycine synthase when it runs in the reverse direction to form glycine. The glycine cleavage system is composed of four proteins: the T-protein, P-protein, L-protein, and H-protein. They do not form a stable complex, so it is more appropriate to call it a "system" instead of a "complex". The H-protein is responsible for interacting with the three other proteins and acts as a shuttle for some of the intermediate products in glycine decarboxylation. In both animals and plants the glycine cleavage system is loosely attached to the inner membrane of the mitochondria. Mutations in this enzymatic system are linked with glycine encephalopathy.
|T-protein (GCST or AMT)||EC 22.214.171.124||aminomethyltransferase|
|P-protein (GLDC)||EC 126.96.36.199||glycine dehydrogenase (decarboxylating) or just glycine dehydrogenase.|
|L-protein (GCSL or DLD)||EC 188.8.131.52||known by many names, but most commonly dihydrolipoyl dehydrogenase|
|H-protein (GCSH)||is modified with lipoic acid and interacts with all other components in a cycle of reductive methylamination (catalysed by the P-protein), methylamine transfer (catalysed by the T-protein) and electron transfer (catalysed by the L-protein).|
In plants, animals and bacteria the glycine cleavage system catalyzes the following reversible reaction:
- Glycine + H4folate + NAD+ ↔ 5,10-methylene-H4folate + CO2 + NH3 + NADH + H+
In the enzymatic reaction, H-protein activates the P-protein, which catalyzes the decarboxylation of glycine and attaches the intermediate molecule to the H-protein to be shuttled to the T-protein. The H-protein forms a complex with the T-protein that uses tetrahydrofolate and yields ammonia and 5,10-methylenetetrahydrofolate. After interaction with the T-protein, the H-protein is left with two fully reduced thiol groups in the lipoate group. The glycine protein system is regenerated when the H-protein is oxidized to regenerate the disulfide bond in the active site by interaction with the L-protein, which reduces NAD+ to NADH and H+.
When coupled to serine hydroxymethyltransferase, the glycine cleavage system overall reaction becomes:
- 2 glycine + NAD+ + H2O → serine + CO2 + NH3 + NADH + H+
In humans and most vertebrates, the glycine cleavage system is part of the most prominent glycine and serine catabolism pathway. This is due in large part to the formation 5,10-methylenetetrahydrofolate, which is one of the few C1 donors in biosynthesis. In this case the methyl group derived from the catabolism of glycine can be transferred to other key molecules such as purines and methionine.
This reaction, and by extension the glycine cleavage system, is required for photorespiration in C3 plants. The glycine cleavage system takes glycine, which is created from an unwanted byproduct of the Calvin cycle, and converts it to serine which can reenter the cycle. The ammonia generated by the glycine cleavage system, is assimilated by the Glutamine synthetase-Glutamine oxoglutarate aminotransferase cycle but costs the cell one ATP and one NADPH. The upside is that one CO2 is produced for every two O2 that are mistakenly taken up by the cell, generating some value in an otherwise energy depleting cycle. Together the proteins involved in these reactions comprise about half the proteins in mitochondria from spinach and pea leaves. The glycine cleavage system is constantly present in the leaves of plants, but in small amounts until they are exposed to light. During peak photosynthesis, the concentration of the glycine cleavage system increases ten-fold.
In the anaerobic bacteria, Clostridium acidiurici, the glycine cleavage system runs mostly in the direction of glycine synthesis. While glycine synthesis through the cleavage system is possible due to the reversibility of the overall reaction, it is not readily seen in animals.
Glycine encephalopathy, also known as non-ketotic hyperglycinemia (NKH), is a primary disorder of the glycine cleavage system, resulting from lowered function of the glycine cleavage system causing increased levels of glycine in body fluids. The disease was first clinically linked to the glycine cleavage system in 1969. Early studies showed high levels of glycine in blood, urine and cerebrospinal fluid. Initial research using carbon labeling showed decreased levels of CO2 and serine production in the liver, pointing directly to deficiencies glycine cleavage reaction. Further research has shown that deletions and mutations in the 5' region of the P-protein are the major genetic causes of nonketotic hyperglycinemia. . In more rare cases, a missense mutation in the genetic code of the T-protein, causing the histidine in position 42 to be mutated to arginine, was also found to result in nonketotic hypergycinemia. This specific mutation directly affected the active site of the T-protein, causing lowered efficiency of the glycine cleavage system.
- Kikuchi G (June 1973). "The glycine cleavage system: composition, reaction mechanism, and physiological significance". Mol. Cell. Biochem. 1 (2): 169–87. doi:10.1007/BF01659328. PMID 4585091.
- Kikuchi G (2008). "The glycine cleavage system: reaction mechanism, physiological significance, and hyperglycinemia". Proc. Jpn. Acad. Ser. B. Phys. Biol. Sci. 84 (7): 246–63. doi:10.2183/pjab.84.246. PMC . PMID 18941301.
- Douce R, Bourguignon J, Neuburger M, Rébeillé F (April 2001). "The glycine decarboxylase system: a fascinating complex". Trends Plant Sci. 6 (4): 167–76. doi:10.1016/S1360-1385(01)01892-1. PMID 11286922.
- Fujiwara K, Okamura K, Motokawa Y (Oct 1979). "Hydrogen carrier protein from chicken liver. Purification, characterization, and role of its prosthetic group, lipoic acid, in the glycine cleavage reaction". Arch. Biochem. Biophys. 197 (2): 454–462. doi:10.1016/0003-9861(79)90267-4. PMID 389161.
- Pares S, Cohen-Addad C, Sicker L, Neuburger M, Douce R (May 1994). "X-ray structure determination at 2.6A˚ resolution of a lipoate-containing protein. The H-protein of the glycine decraboxylase complex from pea leaves". Proc. Natl. Acad. Sci. U.S.A. 91 (11): 4850–3. doi:10.1073/pnas.91.11.4850. PMC . PMID 8197146.
- Fujiwara K, Okamura-Ikeda K, Motokawa Y (Sep 1984). "Mechanism of the glycine cleavage reaction. Further characterization of the intermediate attached to H-protein and of the reaction catalyzed by T-protein". J. Biol. Chem. 259 (17): 10664–8. PMID 6469978.
- Oliver DJ, Neuburger M, Bourguignon J, Douce R (Oct 1990). "Interaction between the component enzymes of the glycine decarboxylase mutienzyme complex". Plant Physiology. 94 (4): 833–839. doi:10.1104/pp.94.2.833. PMC . PMID 16667785.
- Gariboldi RT, Drake HL (May 1984). "Glycine synthase of the purinolytic bacterium Clostridium acidiurici. Purification of the glycine-CO2 exchange system". J. Biol. Chem. 259 (10): 6085–6089. PMID 6427207.
- Kikuchi G, Hiraga K (June 1982). "The mitochondrial glycine cleavage system. Unique features of the glycine decarboxylation". Mol. Cell. Biochem. 45 (3): 137–49. doi:10.1007/bf00230082. PMID 6750353.
- Yoshida T, Kikuchi G, Tada K, Narisawa K, Arakawa T (May 1969). "Physiological significance of glycine cleavage system in human liver as revealed by the study of hyperglycinemia". Biochem. Biophys. Res. Commun. 35 (4): 577–83. doi:10.1016/0006-291x(69)90387-8. PMID 5788511.
- Hayasaka K, Tada K, Fueki N, Nakamura Y (June 1987). "Nonketotic hyperglycinemia: analyses of glycine cleavage system in typical and atypical cases". J. Pediatr. 110 (6): 873–7. doi:10.1016/S0022-3476(87)80399-2. PMID 3585602.
- Kanno J, Hutchin T, Kamada F, Narisawa A, Aoki Y, Matsubara Y, Kure S (Mar 2007). "Genomic deletion within GLDC is a major cause of non-ketotic hyperglycinaemia". Journal of Medical Genetics. 44 (3): e69. doi:10.1136/jmg.2006.043448. PMC . PMID 17361008.
- Kure S, Mandel H, Rolland MO, Sakata Y (April 1998). "A missense mutation (His42Arg) in the T-protein gene from a large Israeli-Arab kindred with nonketotic hyperglycinemia". Hum. Genet. 102 (4): 430–4. doi:10.1007/s004390050716. PMID 9600239.
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.
Aminomethyltransferase folate-binding domain Provide feedback
This is a family of glycine cleavage T-proteins, part of the glycine cleavage multienzyme complex (GCV) found in bacteria and the mitochondria of eukaryotes. GCV catalyses the catabolism of glycine in eukaryotes. The T-protein is an aminomethyl transferase.
McNeil JB, Zhang F, Taylor BV, Sinclair DA, Pearlman RE, Bognar AL; , Gene 1997;186:13-20.: Cloning, and molecular characterization of the GCV1 gene encoding the glycine cleavage T-protein from Saccharomyces cerevisiae. PUBMED:9047339 EPMC:9047339
Internal database links
|SCOOP:||GCV_T_C POPLD SoxG TrmE_N|
|Similarity to PfamA using HHSearch:||SoxG|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR006222
This domain is found at the N terminus of glycine cleavage T-proteins, which are part of the glycine cleavage multienzyme complex (GCV) found in bacteria and the mitochondria of eukaryotes. GCV catalyses the catabolism of glycine in eukaryotes. The T-protein (aminomethyltransferase, EC) is a folate-dependent enzyme that catalyses the release of ammonia and the transfer of the methylene carbon unit (C1 unit) to tetrahydrofolate (H4folate) from the aminomethyl intermediate attached to the lipoate cofactor of H-protein [PUBMED:9047339, PUBMED:16051266].
This domain is also found in YgfZ proteins. YgfZ in E.coli is a folate binding protein involved in RNA modification and regulation of chromosomal replication initiation [PUBMED:16359333]. YgfZ is not an aminomethyltransferase but is likely a folate-dependent regulatory protein [PUBMED:15489424]. This domain could represent a folate-binding domain.
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...
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:||Pfam-B_933 (release 4.0)|
|Author:||Bashton M , Bateman A , Eberhardt R|
|Number in seed:||63|
|Number in full:||17796|
|Average length of the domain:||233.70 aa|
|Average identity of full alignment:||25 %|
|Average coverage of the sequence by the domain:||44.31 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||22|
|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 8 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 GCV_T domain has been found. There are 75 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...