Summary: Cobinamide kinase / cobinamide phosphate guanyltransferase
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Cobalamin biosynthesis Edit Wikipedia article
Cobalamin biosynthesis is the process by which bacteria and archea make cobalamin, vitamin B12. Many steps are involved in converting aminolevulinic acid via uroporphyrinogen III and adenosylcobyric acid to the final forms in which it is used by enzymes in both the producing organisms and other species, including humans who acquire it through their diet.
The feature which distinguishes the two main biosynthetic routes is whether the cobalt that is at the catalytic site in the coenzyme is incorporated early (in anaerobic organisms) or late (in aerobic organisms) and whether oxygen is required. In both cases, the macrocycle that will form a coordination complex with the cobalt ion is a corrin ring, specifically one with seven carboxylate groups called cobyrinic acid. Subsequently, amide groups are formed on all but one of the carboxylates, giving cobyric acid, and the cobalt is liganded with an adenosyl group. In the final part of the biosynthesis, common to all organisms, an aminopropanol sidechain is added to the one free carboxylic group and assembly of the nucleotide loop, which will provide the second ligand for the cobalt, is completed.
Many prokaryotic species cannot biosynthesize adenosylcobalamin, but can make it from cobalamin which they assimilate from external sources. In humans, dietary sources of cobalamin are bound after ingestion as transcobalamins and converted to the coenzyme forms in which they are used.
Cobalamin (vitamin B12) is the largest and most structurally complex vitamin. It consists of a modified tetrapyrrole, a corrin, with a centrally chelated cobalt ion and is usually found in one of two biologically active forms: methylcobalamin and adenosylcobalamin. Most prokaryotes, as well as animals, have cobalamin-dependent enzymes that use it as a cofactor, whereas plants and fungi do not use it. In bacteria and archaea, these enzymes include methionine synthase, ribonucleotide reductase, glutamate and methylmalonyl-CoA mutases, ethanolamine ammonia-lyase, and diol dehydratase. In certain mammals, cobalamin is obtained through the diet, and is required for methionine synthase and methylmalonyl-CoA mutase. In humans, it plays essential roles in folate metabolism and in the synthesis of the citric acid cycle intermediate, succinyl-CoA.
Overview of cobalamin biosynthesis
- Aerobic pathway that requires oxygen and in which cobalt is inserted late in the pathway; found in Pseudomonas denitrificans and Rhodobacter capsulatus.
- Anaerobic pathway in which cobalt insertion is the first committed step towards cobalamin synthesis; found in Salmonella typhimurium, Bacillus megaterium, and Propionibacterium freudenreichii subsp. shermanii.
Either pathway can be divided into two parts:
- Corrin ring synthesis leading to cobyrinic acid, with seven carboxylate groups. In the anaerobic pathway this already contains cobalt but in the aerobic pathway the material formed at that stage is hydrogenobyrinic acid, without the bound cobalt.
- Insertion of cobalt, where not already present; formation of amides on all but one of the carboxylate groups to give cobyric acid; attachment of an adenosyl group as ligand to the cobalt; attachment of an aminopropanol sidechain to the one free carboxylic group and assembly of the nucleotide loop which will provide the second ligand for the cobalt.
A further type of synthesis occurs through a salvage pathway, where outside corrinoids are absorbed to make B12. Species from the following genera and the following individual species are known to synthesize cobalamin: Propionibacterium shermanii, Pseudomonas denitrificans, Streptomyces griseus, Acetobacterium, Aerobacter, Agrobacterium, Alcaligenes, Azotobacter, Bacillus, Clostridium, Corynebacterium, Flavobacterium, Lactobacillus, Micromonospora, Mycobacterium, Nocardia, Proteus, Rhizobium, Salmonella, Serratia, Streptococcus and Xanthomonas.
Detail of steps up to formation of uroporphyrinogen III
In the early steps of the biosynthesis, a tetrapyrrolic structural framework is created by the enzymes deaminase and cosynthetase which transform aminolevulinic acid via porphobilinogen and hydroxymethylbilane to uroporphyrinogen III. The latter is the first macrocyclic intermediate common to haem, chlorophyll, sirohaem and cobalamin itself.
Detail of steps from uroporphyrinogen III to cob(II)yrinic acid a,c-diamide in aerobic organisms
The biosynthesis of cobalamin diverges from that of haem and chlorophyll at uroporphrinogen III: its transformation involves the sequential addition of methyl (CH3) groups to give intermediates that were given trivial names according to the number of these groups that have been incorporated. Hence, the first intermediate is precorrin-1, the next is precorrin-2 and so on. The incorporation of all eight additional methyl groups which occur in cobyric acid was investigated using 13C methyl-labelled S-adenosyl methionine. It was not until scientists at RhÃ´ne-Poulenc Rorer used a genetically-engineered strain of Pseudomonas denitrificans, in which eight of the cob genes involved in the biosynthesis of the vitamin had been overexpressed, that the complete sequence of methylation and other steps could be determined, thus fully establishing all the intermediates in the pathway.
From uroporphyrinogen III to precorrin-2
- (1a) uroporphyrinogen III + S-adenosyl methionine precorrin-1 + S-adenosyl-L-homocysteine
- (1b) precorrin-1 + S-adenosyl methionine precorrin-2 + S-adenosyl-L-homocysteine
From precorrin-2 to precorrin-3A
- precorrin-2 + S-adenosyl methionine precorrin-3A + S-adenosyl-L-homocysteine
From precorrin-3A to precorrin-3B
- precorrin-3A + NADH + H+ + O2 precorrin-3B + NAD+ + H2O
This enzyme is an oxidoreductase that requires oxygen and hence the reaction can only operate under aerobic conditions. The naming of these precorrins as 3A and 3B reflects the fact that each contains three more methyl groups than uroporphyrinogen III but with different structures: in particular, precorrin-3B has an internal Î³-lactone ring formed from the ring A acetic acid sidechain closing back on to the macrocycle.
From precorrin-3B to precorrin-4
- precorrin-3B + S-adenosyl methionine precorrin-4 + S-adenosyl-L-homocysteine
From precorrin-4 to precorrin-5
- precorrin-4 + S-adenosyl methionine precorrin-5 + S-adenosyl-L-homocysteine
The newly-inserted methyl group is added to ring C at the carbon attached to the methylene (CH2) bridge to ring B. This is not its final location on cobalamin as a later step involves its rearrangement to an adjacent ring carbon.
From precorrin-5 to precorrin-6A
- precorrin-5 + S-adenosyl methionine + H2O precorrin-6A + S-adenosyl-L-homocysteine + acetate
This conversion removes the acetyl group located at position 1 of the ring system in precorrin-4 and replaces it with a newly-introduced methyl group. The name of the product, precorrin-6A, reflects the fact that six methyl groups in total have been added to uroporphyrinogen III up to this point. However, since one of these has been extruded with the acetate group, the structure of precorrin-6A contains just the remaining five.
From precorrin-6A to precorrin-6B
- precorrin-6A + NADPH + H+ precorrin-6B + NADP+
Precorrin-6B therefore differs in structure from precorrin-6A only by having an extra two hydrogen atoms.
From precorrin-6B to precorrin-8
The enzyme CobL has two active sites, one catalysing two methyl group additions and the other the decarboxylation of the CH2COOH group on ring D, so that this substituent becomes a simple methyl group EC 126.96.36.199
- precorrin-6B + 2 S-adenosyl methionine precorrin-8X + 2 S-adenosyl-L-homocysteine + CO2
From precorrin-8 to hydrogenobyrinic acid
- precorrin-8X hydrogenobyrinate
The result is that the methyl group that had been added to ring C is isomerised to its final location, an example of intramolecular transfer.
From hydrogenobyrinic acid to hydrogenobyrinic acid a,c-diamide
- hydrogenobyrinic acid + 2 ATP + 2 glutamine + 2 H2O hydrogenobyrinic acid a,c-diamide + 2 ADP + 2 phosphate + 2 glutamic acid
From hydrogenobyrinic acid a,c-diamide to cob(II)yrinic acid a,c-diamide
- hydrogenobyrinic acid a,c-diamide + Co2+ + ATP + H2O cob(II)yrinic acid a,c-diamide + ADP + phosphate + H+
It is at this stage that the aerobic pathway and the anaerobic pathway merge, with later steps being chemically identical.
Detail of steps from uroporphyrinogen III to cob(II)yrinic acid a,c-diamide in anaerobic organisms
Many of the steps beyond uroporphyrinogen III in anaerobic organisms such as Bacillus megaterium involve chemically similar but genetically distinct transformations to those in the aerobic pathway.
From precorrin-2 to cobalt-sirohydrochlorin
The key difference in the pathways is that cobalt is inserted early in anaerobic organisms by first oxidising precorrin-2 to its fully aromatised form sirohydrochlorin and then to that compound's cobalt(II) complex. The reactions are catalysed by CysG EC 188.8.131.52 and Sirohydrochlorin cobaltochelatase EC 184.108.40.206.
From cobalt-sirohydrochlorin to cobalt-factor III
- cobalt-sirohydrochlorin + S-adenosyl methionine cobalt-factor III + S-adenosyl-L-homocysteine
From cobalt-factor III to cobalt-precorrin-4
- cobalt-factor III + S-adenosyl methionine cobalt-precorrin-4 + S-adenosyl-L-homocysteine
In this pathway, the resulting material has contains a Î´-lactone, a six-membered ring, rather than the Î³-lactone (five-membered ring) of precorrin-3B.
From cobalt-precorrin-4 to cobalt-precorrin-5A
- cobalt-precorrin-4 + S-adenosyl methionine cobalt-precorrin-5 + S-adenosyl-L-homocysteine
From cobalt-precorrin-5A to cobalt-precorrin-5B
The scene is now set for the extrusion of the two-carbon fragment corresponding to the acetate released in the formation of precorrin-6A in the aerobic pathway. In this case the fragment released is acetaldehyde and this is catalysed by CbiG in the reaction EC 220.127.116.11
- cobalt-precorrin-5A + H2O cobalt-precorrin-5B + acetaldehyde + 2 H+
From cobalt-precorrin-5B to cob(II)yrinic acid a,c-diamide
The steps from cobalt-precorrin-5B to cob(II)yrinic acid a,c-diamide in the anaerobic pathway are essentially chemically identical to those in the aerobic sequence. The intermediates are called cobalt-precorrin-6A, cobalt-precorrin-6B, cobalt-precorrin-8 and cobyrinic acid and the enzymes / reactions involved are Cobalt-precorrin-5B (C1)-methyltransferase (CbiD / EC 18.104.22.168); Cobalt-precorrin-6A reductase (CbiJ / EC 22.214.171.124); Cobalt-precorrin-7 (C15)-methyltransferase (decarboxylating) (CbiET / EC 126.96.36.199), Cobalt-precorrin-8 methylmutase (CbiC / EC 188.8.131.52) and CbiA / EC 184.108.40.206. The final enzyme forms cob(II)yrinic acid a,c-diamide as the two pathways converge.
Detail of steps from cob(II)yrinic acid a,c-diamide to adenosylcobalamin
Aerobic and anaerobic organisms share the same chemical pathway beyond cob(II)yrinic acid a,c-diamide and this is illustrated for the cob gene products.
From cob(II)yrinic acid a,c-diamide to adenosylcobyric acid
The cobalt(II) is reduced to cobalt(I) by the enzyme Cob(II)yrinic acid a,c-diamide reductase (CobR, reaction EC 220.127.116.11) and then the enzyme Cob(I)yrinic acid a,c-diamide adenosyltransferase (CobO) attaches an adenosyl ligand to the metal in reaction EC 18.104.22.168. Next, the enzyme CobQ (reaction EC 22.214.171.124) converts all the carboxylic acids, except the propionic acid on ring D, to their primary amides.
From adenosylcobyric acid to adenosylcobinamide phosphate
In aerobic organisms, the enzyme CobCD (reaction EC 126.96.36.199) now attaches (R)-1-amino-2-propanol (derived from threonine) to the propionic acid, forming adenosylcobinamide and the enzyme CobU (reaction EC 188.8.131.52) phosphorylates the terminal hydroxy group to form adenosylcobinamide phosphate. The same final product is formed in anaerobic organisms by direct reaction of adenosylcobyric acid with (R)-1-amino-2-propanol O-2-phosphate (derived from threonine-O-phosphate by the enzyme CobD in reaction EC 184.108.40.206) catalysed by the enzyme CbiB.
From adenosylcobinamide phosphate to adenosylcobalamin
In a separate branch of the pathway, 5,6-dimethylbenzimidazole is biosynthesised from flavin mononucleotide by the enzyme 5,6-dimethylbenzimidazole synthase (reaction EC 220.127.116.11) and converted by CobT in reaction EC 18.104.22.168 to alpha-ribazole 5' phosphate. Then the enzyme CobU (reaction EC 22.214.171.124) activates adenosylcobinamide phosphate by formation of adenosylcobinamide-GDP and CobV (reaction EC 126.96.36.199) links the two substrates to form Adenosylcobalamin-5'-phosphate. In the final step to the coenzyme, CobC removes the 5' phosphate group in the reaction EC 188.8.131.52
- Adenosylcobalamin-5'-phosphate + H2O adenosylcobalamin + phosphate
The complete biosynthetic route involves a long linear path that requires about 25 contributing enzyme steps.
Other pathways of cobalamin metabolism
Salvage pathways in prokaryotes
Many prokaryotic species cannot biosynthesize adenosylcobalamin, but can make it from cobalamin. These organisms are capable of cobalamin transport into the cell and its conversion to the required coenzyme form. Even organisms such as Salmonella typhimurium that can make cobalamin also assimilate it from external sources when available. Uptake into cells is facilitated by ABC transporters which absorb the cobalamin through the cell membrane.
Cobalamin metabolism in humans
In humans, dietary sources of cobalamin are bound after ingestion as transcobalamins. They are then converted to the coenzyme forms in which they are used. Methylmalonic aciduria and homocystinuria type C protein is the enzyme which catalyzes the decyanation of cyanocobalamin as well as the dealkylation of alkylcobalamins including methylcobalamin and adenosylcobalamin.
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- Hannibal, Luciana; Kim, Jihoe; Brasch, Nicola E.; Wang, Sihe; Rosenblatt, David S.; Banerjee, Ruma; Jacobsen, Donald W. (2009). "Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (CBLC) gene product". Molecular Genetics and Metabolism. 97 (4): 260â€“266. doi:10.1016/j.ymgme.2009.04.005. PMCÂ 2709701. PMIDÂ 19447654.
- Banerjee, Ruma; Gherasim, Carmen; Padovani, Dominique (2009). "The tinker, tailor, soldier in intracellular B12 trafficking". Current Opinion in Chemical Biology. 13 (4): 484â€“491. doi:10.1016/j.cbpa.2009.07.007. PMCÂ 5750051. PMIDÂ 19665918.
- Quadros, Edward V. (2010). "Advances in the understanding of cobalamin assimilation and metabolism". British Journal of Haematology. 148 (2): 195â€“204. doi:10.1111/j.1365-2141.2009.07937.x. PMCÂ 2809139. PMIDÂ 19832808.
- Layer, Gunhild; Jahn, Dieter; Deery, Evelyne; Lawrence, Andrew D.; Warren, Martin J. (2010). "Biosynthesis of Heme and Vitamin B12". Comprehensive Natural Products II. pp.Â 445â€“499. doi:10.1016/B978-008045382-8.00144-1. ISBNÂ 9780080453828.
- Prof Sir Alan Battersby: the biosynthesis of Vitamin B12 St. Catharine's College, Cambridge, video
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.
Cobinamide kinase / cobinamide phosphate guanyltransferase Provide feedback
This family is composed of a group of bifunctional cobalamin biosynthesis enzymes which display cobinamide kinase and cobinamide phosphate guanyltransferase activity. The crystal structure of the enzyme reveals the molecule to be a trimer with a propeller-like shape .
Thompson TB, Thomas MG, Escalante-Semerena JC, Rayment I; , Biochemistry 1998;37:7686-7695.: Three-dimensional structure of adenosylcobinamide kinase/adenosylcobinamide phosphate guanylyltransferase from Salmonella typhimurium determined to 2.3 A resolution,. PUBMED:9601028 EPMC:9601028
Internal database links
|SCOOP:||AAA AAA_14 AAA_16 AAA_18 AAA_22 AAA_24 AAA_25 ATPase ATPase_2 CPT DnaB_C Rad51 RecA|
|Similarity to PfamA using HHSearch:||AAA ATPase SpoIVA_ATPase AAA_18 AAA_24 AAA_25 AAA_29 AAA_33|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR003203
This family is composed of a group of bifunctional cobalamin biosynthesis enzymes which display cobinamide kinase and cobinamide phosphate guanyltransferase activity. The crystal structure of the enzyme reveals the molecule to be a trimer with a propeller-like shape [ PUBMED:9601028 ].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||nucleotide binding (GO:0000166)|
|adenosylcobinamide kinase activity (GO:0043752)|
|Biological process||cobalamin biosynthetic process (GO:0009236)|
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...
AAA family proteins often perform chaperone-like functions that assist in the assembly, operation, or disassembly of protein complexes .
The clan contains the following 245 members:6PF2K AAA AAA-ATPase_like AAA_10 AAA_11 AAA_12 AAA_13 AAA_14 AAA_15 AAA_16 AAA_17 AAA_18 AAA_19 AAA_2 AAA_21 AAA_22 AAA_23 AAA_24 AAA_25 AAA_26 AAA_27 AAA_28 AAA_29 AAA_3 AAA_30 AAA_31 AAA_32 AAA_33 AAA_34 AAA_35 AAA_5 AAA_6 AAA_7 AAA_8 AAA_9 AAA_PrkA ABC_ATPase ABC_tran ABC_tran_Xtn Adeno_IVa2 Adenylsucc_synt ADK AFG1_ATPase AIG1 APS_kinase Arf ArsA_ATPase ATP-synt_ab ATP_bind_1 ATP_bind_2 ATPase ATPase_2 Bac_DnaA BCA_ABC_TP_C Beta-Casp bpMoxR BrxC_BrxD BrxL_ATPase Cas_Csn2 Cas_St_Csn2 CbiA CBP_BcsQ CDC73_C CENP-M CFTR_R CLP1_P CMS1 CoaE CobA_CobO_BtuR CobU cobW CPT CSM2 CTP_synth_N Cytidylate_kin Cytidylate_kin2 DAP3 DEAD DEAD_2 divDNAB DLIC DNA_pack_C DNA_pack_N DNA_pol3_delta DNA_pol3_delta2 DnaB_C dNK DO-GTPase1 DO-GTPase2 DUF1611 DUF2075 DUF2326 DUF2478 DUF257 DUF2813 DUF3584 DUF463 DUF4914 DUF5906 DUF6079 DUF815 DUF835 DUF87 DUF927 Dynamin_N Dynein_heavy Elong_Iki1 ELP6 ERCC3_RAD25_C Exonuc_V_gamma FeoB_N Fer4_NifH Flavi_DEAD FTHFS FtsK_SpoIIIE G-alpha Gal-3-0_sulfotr GBP GBP_C GpA_ATPase GpA_nuclease GTP_EFTU Gtr1_RagA Guanylate_kin GvpD_P-loop HDA2-3 Helicase_C Helicase_C_2 Helicase_C_4 Helicase_RecD HerA_C Herpes_Helicase Herpes_ori_bp Herpes_TK HydF_dimer HydF_tetramer Hydin_ADK IIGP IPPT IPT iSTAND IstB_IS21 KAP_NTPase KdpD Kinase-PPPase Kinesin KTI12 LAP1_C LpxK MCM MeaB MEDS Mg_chelatase Microtub_bd MipZ MMR_HSR1 MMR_HSR1_C MobB MukB Mur_ligase_M MutS_V Myosin_head NACHT NAT_N NB-ARC NOG1 NTPase_1 NTPase_P4 ORC3_N P-loop_TraG ParA Parvo_NS1 PAXNEB PduV-EutP PhoH PIF1 Ploopntkinase1 Ploopntkinase2 Ploopntkinase3 Podovirus_Gp16 Polyoma_lg_T_C Pox_A32 PPK2 PPV_E1_C PRK PSY3 Rad17 Rad51 Ras RecA ResIII RHD3_GTPase RhoGAP_pG1_pG2 RHSP RNA12 RNA_helicase Roc RsgA_GTPase RuvB_N SbcC_Walker_B SecA_DEAD Senescence Septin Sigma54_activ_2 Sigma54_activat SKI SMC_N SNF2-rel_dom SpoIVA_ATPase Spore_III_AA SRP54 SRPRB SulA Sulfotransfer_1 Sulfotransfer_2 Sulfotransfer_3 Sulfotransfer_4 Sulfotransfer_5 Sulphotransf SWI2_SNF2 T2SSE T4SS-DNA_transf TerL_ATPase Terminase_3 Terminase_6N Thymidylate_kin TIP49 TK TmcA_N TniB Torsin TraG-D_C tRNA_lig_kinase TrwB_AAD_bind TsaE UvrB UvrD-helicase UvrD_C UvrD_C_2 Viral_helicase1 VirC1 VirE YqeC Zeta_toxin Zot
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 and the UniProtKB 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
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_7022 (release 5.2)|
|Author:||Mian N , Bateman A|
|Number in seed:||112|
|Number in full:||4935|
|Average length of the domain:||162.20 aa|
|Average identity of full alignment:||33 %|
|Average coverage of the sequence by the domain:||80.03 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -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.
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 CobU domain has been found. There are 6 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...
AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.
|Protein||Predicted structure||External Information|
|O53676||View 3D Structure||Click here|
|P0AE76||View 3D Structure||Click here|
|P0AE77||View 3D Structure||Click here|
|Q05599||View 3D Structure||Click here|
|Q9I466||View 3D Structure||Click here|