Summary: Glyceraldehyde 3-phosphate dehydrogenase, NAD 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 "Glyceraldehyde 3-phosphate dehydrogenase". 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.
Glyceraldehyde 3-phosphate dehydrogenase Edit Wikipedia article
GAPDH with NAD+ and Pi bound to the active site. PDB rendering based on .
|Symbols||; G3PD; GAPD; HEL-S-162eP|
|External IDs||ChEMBL: GeneCards:|
|RNA expression pattern|
|Glyceraldehyde 3-phosphate dehydrogenase, NAD binding domain|
determinants of enzyme thermostability observed in the molecular structure of thermus aquaticus d-glyceraldehyde-3-phosphate dehydrogenase at 2.5 angstroms resolution
|Glyceraldehyde 3-phosphate dehydrogenase, C-terminal domain|
crystal structure of glyceraldehyde-3-phosphate dehydrogenase from pyrococcus horikoshii ot3
Glyceraldehyde 3-phosphate dehydrogenase (abbreviated as GAPDH or less commonly as G3PDH) (EC 220.127.116.11) is an enzyme of ~37kDa that catalyzes the sixth step of glycolysis and thus serves to break down glucose for energy and carbon molecules. In addition to this long established metabolic function, GAPDH has recently been implicated in several non-metabolic processes, including transcription activation, initiation of apoptosis, ER to Golgi vesicle shuttling, and fast axonal, or axoplasmic transport.
- 1 Metabolic function
- 2 Additional functions
- 3 Metabolic switch
- 4 Cellular location
- 5 Usage of GAPDH as loading control
- 6 References
- 7 Further reading
As its name indicates, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) catalyses the conversion of glyceraldehyde 3-phosphate to D-glycerate 1,3-bisphosphate. This is the 6th step in the glycolytic breakdown of glucose, an important pathway of energy and carbon molecule supply which takes place in the cytosol of eukaryotic cells. The conversion occurs in two coupled steps. The first is favourable and allows the second unfavourable step to occur.
Overall reaction catalyzed
|glyceraldehyde 3-phosphate||glyceraldehyde phosphate dehydrogenase||D-glycerate 1,3-bisphosphate|
|NAD+ + Pi||NADH + H+|
|NAD+ + Pi||NADH + H+|
Two-step conversion of glyceraldehyde-3-phosphate
The first reaction is the oxidation of glyceraldehyde 3-phosphate at the carbon 1 position (the 4th carbon from glycolysis which is shown in the diagram), in which an aldehyde is converted into a carboxylic acid (ΔG°'=-50 kJ/mol (-12kcal/mol)) and NAD+ is simultaneously reduced endergonically to NADH.
The energy released by this highly exergonic oxidation reaction drives the endergonic second reaction (ΔG°'=+50 kJ/mol (+12kcal/mol)), in which a molecule of inorganic phosphate is transferred to the GAP intermediate to form a product with high phosphoryl-transfer potential: 1,3-bisphosphoglycerate (1,3-BPG).
This is an example of phosphorylation coupled to oxidation, and the overall reaction is somewhat endergonic (ΔG°'=+6.3 kJ/mol (+1.5)). Energy coupling here is made possible by GAPDH.
Mechanism of catalysis
GAPDH uses covalent catalysis and general base catalysis to decrease the very large and positive activation energy of the second step of this reaction. First, a cysteine residue in the active site of GAPDH attacks the carbonyl group of GAP, creating a hemithioacetal intermediate (covalent catalysis). Next, an adjacent, tightly bound molecule of NAD+ accepts a hydride ion from GAP, forming NADH; GAP is concomitantly oxidized to a thioester intermediate using a molecule of water. This thioester species is much higher in energy than the carboxylic acid species that would result in the absence of GAPDH (the carboxylic acid species is so low in energy that the energy barrier for the second step of the reaction (phosphorylation) would be too great, and the reaction therefore too slow and equilibrium too unfavorable, for a living organism). Donation of the hydride ion by the hemithioacetal is facilitated by its deprotonation by a histidine residue in the enzyme's active site (general base catalysis). Deprotonation encourages the reformation of the carbonyl group in the thioester intermediate and ejection of the hydride ion. NADH leaves the active site and is replaced by another molecule of NAD+, the positive charge of which stabilizes the negatively charged carbonyl oxygen in the transition state of the next and ultimate step. Finally, a molecule of inorganic phosphate attacks the thioester and forms a tetrahedral intermediate, which then collapses to release 1,3-bisphosphoglycerate, and the thiol group of the enzyme's cysteine residue.
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
- The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534".
GAPDH, like many other enzymes, has multiple functions. In addition to catalysing the 6th step of glycolysis, recent evidence implicates GAPDH in other cellular processes. This came as a surprise to researchers but it makes evolutionary sense to re-use and adapt existing proteins instead of evolving a novel protein from scratch.
GAPDH can also be inhibited by arsenate, inhibiting glycolysis in red blood cells and causing hemolytic anemia.
Transcription and apoptosis
Zheng et al. discovered in 2003 that GAPDH can itself activate transcription. The OCA-S transcriptional coactivator complex contains GAPDH and lactate dehydrogenase, two proteins previously only thought to be involved in metabolism. GAPDH moves between the cytosol and the nucleus and may thus link the metabolic state to gene transcription. 
In 2005, Hara et al. showed that GAPDH initiates apoptosis. This is not a third function, but can be seen as an activity mediated by GAPDH binding to DNA like in transcription activation, discussed above. The study demonstrated that GAPDH is S-nitrosylated by NO in response to cell stress, which causes it to bind to the protein SIAH1, a ubiquitin ligase. The complex moves into the nucleus where Siah1 targets nuclear proteins for degradation, thus initiating controlled cell shutdown. In subsequent study the group demonstrated that deprenyl, which has been used clinically to treat Parkinson's disease, strongly reduces the apoptotic action of GAPDH by preventing its S-nitrosylation and might thus be used as a drug.
GAPDH acts as reversible metabolic switch under oxidative stress. When cells are exposed to oxidants, they need excessive amounts of the antioxidant cofactor NADPH. In the cytosol, NADPH is reduced from NADP+ by several enzymes, three of them catalyze the first steps of the Pentose phosphate pathway. Oxidant-treatments cause an inactivation of GAPDH. This inactivation re-routes temporally the metabolic flux from glycolysis to the Pentose Phosphate Pathway, allowing the cell to generate more NADPH. Under stress conditions, NADPH is needed by some antioxidant-systems including glutaredoxin and thioredoxin as well as being essential for the recycling of gluthathione.
ER to Golgi transport
GAPDH also appears to be involved in the vesicle transport from the endoplasmic reticulum (ER) to the Golgi apparatus which is part of shipping route for secreted proteins. It was found that GAPDH is recruited by rab2 to the vesicular-tubular clusters of the ER where it helps to form COP 1 vesicles. GAPDH is activated via tyrosine phosphorylation by Src.
All steps of glycolysis take place in the cytosol and so does the reaction catalysed by GAPDH. Research in red blood cells indicates that GAPDH and several other glycolytic enzymes assemble in complexes on the inside of the cell membrane. The process appears to be regulated by phosphorylation and oxygenation. Bringing several glycolytic enzymes close to each other is expected to greatly increase the overall speed of glucose breakdown.
Usage of GAPDH as loading control
Because the GAPDH gene is often stably and constitutively expressed at high levels in most tissues and cells, it is considered a housekeeping gene. For this reason, GAPDH is commonly used by biological researchers as a loading control for western blot and as a control for qPCR. However, researchers have reported different regulation of GAPDH under specific conditions. Therefore, the use of GAPDH as loading control has to be controlled carefully.
- Tarze A, Deniaud A, Le Bras M, Maillier E, Molle D, Larochette N, Zamzami N, Jan G, Kroemer G, Brenner C (April 2007). "GAPDH, a novel regulator of the pro-apoptotic mitochondrial membrane permeabilization". Oncogene 26 (18): 2606–20. doi:10.1038/sj.onc.1210074. PMID 17072346.
- Zala D, Hinckelmann MV, Yu H, Lyra da Cunha MM, Liot G, Cordelières FP, Marco S, Saudou F (January 2013). "Vesicular glycolysis provides on-board energy for fast axonal transport". Cell 152 (3): 479–91. doi:10.1016/j.cell.2012.12.029. PMID 23374344.
- Selwood T, Jaffe EK (March 2012). "Dynamic dissociating homo-oligomers and the control of protein function". Arch. Biochem. Biophys. 519 (2): 131–43. doi:10.1016/j.abb.2011.11.020. PMC 3298769. PMID 22182754.
- Zheng L, Roeder RG, Luo Y (2003). "S phase activation of the histone H2B promoter by OCA-S, a coactivator complex that contains GAPDH as a key component". Cell 114 (2): 255–66. doi:10.1016/S0092-8674(03)00552-X. PMID 12887926.
- Hara MR, Agrawal N, Kim SF, Cascio MB, Fujimuro M, Ozeki Y, Takahashi M, Cheah JH, Tankou SK, Hester LD, Ferris CD, Hayward SD, Snyder SH, Sawa A (July 2005). "S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding". Nat. Cell Biol. 7 (7): 665–74. doi:10.1038/ncb1268. PMID 15951807.
- Hara MR, Thomas B, Cascio MB, Bae BI, Hester LD, Dawson VL, Dawson TM, Sawa A, Snyder SH (March 2006). "Neuroprotection by pharmacologic blockade of the GAPDH death cascade". Proc. Natl. Acad. Sci. U.S.A. 103 (10): 3887–9. doi:10.1073/pnas.0511321103. PMC 1450161. PMID 16505364.
- Agarwal AR, Zhao L, Sancheti H, Sundar IK, Rahman I, Cadenas E. "Short-term cigarette smoke exposure induces reversible changes in energy metabolism and cellular redox status independent of inflammatory responses in mouse lungs". Am J Physiol Lung Cell Mol Physiol 10: L889-98 year = 2012. doi:10.1152/ajplung. PMID 23064950.
- Ralser M, Wamelink MM, Kowald A, Gerisch B, Heeren G, Struys EA, Klipp E, Jakobs C, Breitenbach M, Lehrach H, Krobitsch S (2007). "Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress". J. Biol. 6 (4): 10. doi:10.1186/jbiol61. PMC 2373902. PMID 18154684.
- Tisdale EJ, Artalejo CR (June 2007). "A GAPDH mutant defective in Src-dependent tyrosine phosphorylation impedes Rab2-mediated events". Traffic 8 (6): 733–41. doi:10.1111/j.1600-0854.2007.00569.x. PMID 17488287.
- Campanella ME, Chu H, Low PS (February 2005). "Assembly and regulation of a glycolytic enzyme complex on the human erythrocyte membrane". Proc. Natl. Acad. Sci. U.S.A. 102 (7): 2402–7. doi:10.1073/pnas.0409741102. PMC 549020. PMID 15701694.
- Barber RD, Harmer DW, Coleman RA, Clark BJ (May 2005). "GAPDH as a housekeeping gene: analysis of GAPDH mRNA expression in a panel of 72 human tissues". Physiol. Genomics 21 (3): 389–95. doi:10.1152/physiolgenomics.00025.2005. PMID 15769908.
- Voet D, Voet JG (2010). Biochemistry. New York: Wiley. ISBN 0-470-57095-4.
- Stryer, Lubert; Berg, Jeremy Mark; Tymoczko, John L. (2002). Biochemistry, Fifth Edition & Lecture Notebook. San Francisco: W. H. Freeman. ISBN 0-7167-9804-2.
- diagram of the GAPDH reaction mechanism from Lodish MCB at NCBI bookshelf
- similar diagram from Alberts The Cell at NCBI bookshelf
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.
Glyceraldehyde 3-phosphate dehydrogenase, NAD binding domain Provide feedback
GAPDH is a tetrameric NAD-binding enzyme involved in glycolysis and glyconeogenesis. N-terminal domain is a Rossmann NAD(P) binding fold.
Kim H, Feil IK, Verlinde CL, Petra PH, Hol WG; , Biochemistry 1995;34:14975-14986.: Crystal structure of glycosomal glyceraldehyde-3-phosphate dehydrogenase from Leishmania mexicana: implications for structure-based drug design and a new position for the inorganic phosphate binding site. PUBMED:7578111 EPMC:7578111
Internal database links
|Similarity to PfamA using HHSearch:||DapB_N GFO_IDH_MocA 2-Hacid_dh_C NAD_binding_3 Semialdhyde_dh|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR020828
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays an important role in glycolysis and gluconeogenesis [PUBMED:2716055] by reversibly catalysing the oxidation and phosphorylation of D-glyceraldehyde-3-phosphate to 1,3-diphospho-glycerate. The enzyme exists as a tetramer of identical subunits, each containing 2 conserved functional domains: an NAD-binding domain, and a highly conserved catalytic domain [PUBMED:6303388]. The enzyme has been found to bind to actin and tropomyosin, and may thus have a role in cytoskeleton assembly. Alternatively, the cytoskeleton may provide a framework for precise positioning of the glycolytic enzymes, thus permitting efficient passage of metabolites from enzyme to enzyme [PUBMED:6303388].
GAPDH displays diverse non-glycolytic functions as well, its role depending upon its subcellular location. For instance, the translocation of GAPDH to the nucleus acts as a signalling mechanism for programmed cell death, or apoptosis [PUBMED:10740219]. The accumulation of GAPDH within the nucleus is involved in the induction of apoptosis, where GAPDH functions in the activation of transcription. The presence of GAPDH is associated with the synthesis of pro-apoptotic proteins like BAX, c-JUN and GAPDH itself.
GAPDH has been implicated in certain neurological diseases: GAPDH is able to bind to the gene products from neurodegenerative disorders such as Huntington's disease, Alzheimer's disease, Parkinson's disease and Machado-Joseph disease through stretches encoded by their CAG repeats. Abnormal neuronal apoptosis is associated with these diseases. Propargylamines such as deprenyl increase neuronal survival by interfering with apoptosis signalling pathways via their binding to GAPDH, which decreases the synthesis of pro-apoptotic proteins [PUBMED:12721812].
This entry represents the N-terminal domain which is a Rossmann NAD(P) binding fold.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor (GO:0016620)|
|Biological process||oxidation-reduction process (GO:0055114)|
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...
A class of redox enzymes are two domain proteins. One domain, termed the catalytic domain, confers substrate specificity and the precise reaction of the enzyme. The other domain, which is common to this class of redox enzymes, is a Rossmann-fold domain. The Rossmann domain binds nicotinamide adenine dinucleotide (NAD+) and it is this cofactor that reversibly accepts a hydride ion, which is lost or gained by the substrate in the redox reaction. Rossmann domains have an alpha/beta fold, which has a central beta sheet, with approximately five alpha helices found surrounding the beta sheet.The strands forming the beta sheet are found in the following characteristic order 654123. The inter sheet crossover of the stands in the sheet form the NAD+ binding site . In some more distantly relate Rossmann domains the NAD+ cofactor is replaced by the functionally similar cofactor FAD.
The clan contains the following 180 members:2-Hacid_dh_C 3Beta_HSD 3HCDH_N adh_short adh_short_C2 ADH_zinc_N ADH_zinc_N_2 AdoHcyase_NAD AdoMet_MTase AlaDh_PNT_C Amino_oxidase ApbA AviRa Bac_GDH Bin3 CheR CMAS CmcI CoA_binding CoA_binding_2 CoA_binding_3 Cons_hypoth95 DAO DapB_N DFP DNA_circ_N DNA_methylase DOT1 DREV dTMP_synthase DUF1442 DUF1776 DUF2431 DUF268 DUF3321 DUF43 DUF633 DUF938 DXP_redisom_C DXP_reductoisom Eco57I ELFV_dehydrog Eno-Rase_FAD_bd Eno-Rase_NADH_b Enoyl_reductase Epimerase F420_oxidored FAD_binding_2 FAD_binding_3 FAD_oxidored Fibrillarin FMO-like FmrO FtsJ G-7-MTase G6PD_N GCD14 GDI GFO_IDH_MocA GIDA GidB GLF Glyco_hydro_4 GMC_oxred_N Gp_dh_N GRAS GRDA HI0933_like HIM1 IlvN K_oxygenase KR LCM Ldh_1_N Lycopene_cycl Malic_M Mannitol_dh Met_10 Methyltrans_Mon Methyltrans_SAM Methyltransf_10 Methyltransf_11 Methyltransf_12 Methyltransf_15 Methyltransf_16 Methyltransf_17 Methyltransf_18 Methyltransf_19 Methyltransf_2 Methyltransf_20 Methyltransf_21 Methyltransf_22 Methyltransf_23 Methyltransf_24 Methyltransf_25 Methyltransf_26 Methyltransf_27 Methyltransf_28 Methyltransf_29 Methyltransf_3 Methyltransf_30 Methyltransf_31 Methyltransf_32 Methyltransf_4 Methyltransf_5 Methyltransf_7 Methyltransf_8 Methyltransf_9 Methyltransf_PK MethyltransfD12 MetW Mg-por_mtran_C Mqo MT-A70 MTS Mur_ligase N2227 N6-adenineMlase N6_Mtase N6_N4_Mtase NAD_binding_10 NAD_binding_11 NAD_binding_2 NAD_binding_3 NAD_binding_4 NAD_binding_5 NAD_binding_7 NAD_binding_8 NAD_binding_9 NAD_Gly3P_dh_N NAS NmrA NNMT_PNMT_TEMT NodS Nol1_Nop2_Fmu Nol1_Nop2_Fmu_2 NSP13 OCD_Mu_crystall PARP_regulatory PCMT PDH Polysacc_synt_2 Pox_MCEL Prenylcys_lyase PrmA PRMT5 Pyr_redox Pyr_redox_2 Pyr_redox_3 RmlD_sub_bind Rossmann-like rRNA_methylase RrnaAD Rsm22 RsmJ Saccharop_dh SAM_MT SE Semialdhyde_dh Shikimate_DH Spermine_synth Strep_67kDa_ant TehB THF_DHG_CYH_C Thi4 ThiF TPMT TrkA_N TRM TRM13 tRNA_U5-meth_tr Trp_halogenase TylF Ubie_methyltran UDPG_MGDP_dh_N UPF0020 UPF0146 V_cholerae_RfbT XdhC_C YjeF_N
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...
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 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.
- Pfam viewer
- an HTML-based viewer that uses DAS to retrieve alignment fragments on request
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.
MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.
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:||Eddy SR, Griffiths-Jones SR|
|Number in seed:||112|
|Number in full:||14213|
|Average length of the domain:||130.00 aa|
|Average identity of full alignment:||46 %|
|Average coverage of the sequence by the domain:||43.38 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||19|
|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 2 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 Gp_dh_N domain has been found. There are 412 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...