Summary: Precorrin-6x reductase CbiJ/CobK
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 "Cobalamin biosynthesis". 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.
Cobalamin biosynthesis Edit Wikipedia article
adenosylcobinamide kinase/adenosylcobinamide phosphate guanylyltransferase (cobu) from salmonella typhimurium
|CobW C terminal|
dethiobiotin synthetase complexed with 7,8-diamino-nonanoic acid, 5'-adenosyl-methylene-triphosphate, and manganese
structural genomics, 1.9a crystal structure of cobalamin biosynthesis protein (cbid) from archaeoglobus fulgidus
|CbiG N terminus|
|CbiG central region|
|CbiG C terminus|
crystal structure of hypothetical protein af0721 from archaeoglobus fulgidus
In molecular biology, cobalamin biosynthesis is the synthesis of cobalamin (vitamin B12).
Cobalamin (vitamin B12) is a structurally complex cofactor, consisting of a modified tetrapyrrole with a centrally chelated cobalt. Cobalamin is usually found in one of two biologically active forms: methylcobalamin and adenosylcobalamin. Most prokaryotes, as well as animals, have cobalamin-dependent enzymes, whereas plants and fungi do not appear to 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.
Pathways 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 (differs in aerobic and anaerobic pathways)
- Adenosylation of corrin ring, attachment of aminopropanol arm, and assembly of the nucleotide loop (common to both pathways).
Proteins involved in cobalamin biosynthesis
There are about 30 enzymes involved in either pathway, where those involved in the aerobic pathway are prefixed Cob and those of the anaerobic pathway Cbi. Several of these enzymes are pathway-specific: CbiD, CbiG, and CbiK are specific to the anaerobic route of S. typhimurium, whereas CobE, CobF, CobG, CobN, CobS, CobT, and CobW are unique to the aerobic pathway of P. denitrificans.
Aerobic cobalt chelatase consists of three subunits, CobT, CobN and CobS. Cobalamin (vitamin B12) can be complexed with metal via the ATP-dependent reactions (aerobic pathway) (e.g., in P. denitrificans) or via ATP-independent reactions (anaerobic pathway) (e.g., in Salmonella typhimurium). The corresponding cobalt chelatases are not homologous. However, aerobic cobalt chelatase subunits CobN and CobS are homologous to Mg-chelatase subunits BchH and BchI, respectively. CobT, too, has been found to be remotely related to the third subunit of Mg-chelatase, BchD (involved in bacteriochlorophyll synthesis, e.g., in Rhodobacter capsulatus).
The CobS protein is a cobalamin-5-phosphate synthase that catyalzes the reactions:
- Adenosylcobinamide-GDP + alpha-ribazole-5'-P = adenosylcobalamin-5'-phosphate + GMP
- Adenosylcobinamide-GDP + alpha-ribazole = adenosylcobalamin + GMP
The protein product from these catalyses is associated with a large complex of proteins and is induced by cobinamide. CobS is involved in part III of cobalamin biosynthesis, one of the late steps in adenosylcobalamin synthesis that, together with CobU, CobT, and CobC proteins, defines the nucleotide loop assembly pathway.
CobU proteins are bifunctional cobalbumin 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.
CobW proteins are generally found proximal to the trimeric cobaltochelatase subunit CobN, which is essential for vitamin B12 (cobalamin) biosynthesis. They contain a P-loop nucleotide-binding loop in the N-terminal domain and a histidine-rich region in the C-terminal portion suggesting a role in metal binding, possibly as an intermediary between the cobalt transport and chelation systems. CobW might be involved in cobalt reduction leading to cobalt(I) corrinoids. CobW-like proteins include P47K, a Pseudomonas chlororaphis protein needed for nitrile hydratase expression, and urease accessory protein UreG, which acts as a chaperone in the activation of urease upon insertion of nickel into the active site.
The CbiA family of proteins consists of various cobyrinic acid a,c-diamide synthases. These include CbiA and CbiP from Salmonella typhimurium., and CobQ from Rhodobacter capsulatus. These amidases catalyse amidations to various side chains of hydrogenobyrinic acid or cobyrinic acid a,c-diamide in the biosynthesis of cobalamin (vitamin B12) from uroporphyrinogen III.
CbiD is an essential protein for cobalamin biosynthesis in both Salmonella typhimurium and Bacillus megaterium. A deletion mutant of CbiD suggests that this enzyme is involved in C-1 methylation and deacylation reactions required during the ring contraction process in the anaerobic pathway to cobalamin (similar role as CobF). The CbiD protein has a putative S-AdoMet binding site. CbiD has no counterpart in the aerobic pathway.
CbiG proteins are specific for anaerobic cobalamin biosynthesis. CbiG, which shows homology with CobE of the aerobic pathway, participates in the conversion of cobalt-precorrin 5 into cobalt-precorrin 6. CbiG is responsible for the opening of the delta-lactone ring and extrusion of the C2-unit. The aerobic pathway uses molecular oxygen to trigger the events at C-20 leading to contraction and expulsion of the C2-unit as acetic acid from a metal-free intermediate, whereas the anaerobic route involves the internal delivery of oxygen from a carboxylic acid terminus to C-20 followed by extrusion of the C2-unit as acetaldehyde, using cobalt complexes as substrates.
The CbiJ family of proteins includes the CobK and CbiJ precorrin-6x reductases EC 220.127.116.11. In the aerobic pathway, CobK catalyses the reduction of the macrocycle of precorrin-6X to produce precorrin-6Y; while in the anaerobic pathway CbiJ catalyses the reduction of the macrocycle of cobalt-precorrin-6X into cobalt-precorrin-6Y.
CbiM is a transmembrane cobalamin transporter.
The cobalt transport protein CbiN is part of the active cobalt transport system involved in uptake of cobalt into the cell involved with cobalamin biosynthesis (vitamin B12). It has been suggested that CbiN may function as the periplasmic binding protein component of the active cobalt transport system.
The CbiQ family consists of various cobalt transport proteins Most of which are found in Cobalamin (Vitamin B12) biosynthesis operons. In Salmonella the cbiN cbiQ (product CbiQ in this family) and cbiO are likely to form an active cobalt transport system.
The CbiX protein functions as a cobalt-chelatase in the anaerobic biosynthesis of cobalamin. It catalyses the insertion of cobalt into sirohydrochlorin. The structure of CbiX from Archaeoglobus fulgidus consists of a central mixed beta-sheet flanked by four alpha-helices, although it is about half the size of other Class II tetrapyrrole chelatases. The CbiX proteins found in archaea appear to be shorter than those found in eubacteria.
The CbiZ family of proteins includes CbiZ, which is involved in the salvage pathway of cobinamide in archaea. Archaea convert adenosylcobinamide (AdoCbi) into adenosylcobinamide phosphate (AdoCbi-P) in two steps. First, the amidohydrolase activity of CbiZ cleaves off the aminopropanol moiety of AdoCbi yielding adenosylcobyric acid (AdoCby); second, AdoCby is converted into AdoCbi-P by the action of adenosylcobinamide-phosphate synthase (CbiB). Adenosylcobyric acid is an intermediate of the de novo coenzyme B12 biosynthetic route.
- Rodionov DA, Vitreschak AG, Mironov AA, Gelfand MS (October 2003). "Comparative genomics of the vitamin B12 metabolism and regulation in prokaryotes". J. Biol. Chem. 278 (42): 41148–59. doi:10.1074/jbc.M305837200. PMID 12869542.
- Banerjee R (April 2006). "B12 trafficking in mammals: A for coenzyme escort service". ACS Chem. Biol. 1 (3): 149–59. doi:10.1021/cb6001174. PMID 17163662.
- Roessner CA, Santander PJ, Scott AI (2001). "Multiple biosynthetic pathways for vitamin B12: variations on a central theme". Vitam. Horm. 61: 267–97. doi:10.1016/s0083-6729(01)61009-4. PMID 11153269.
- Heldt D, Lawrence AD, Lindenmeyer M, Deery E, Heathcote P, Rigby SE, Warren MJ (August 2005). "Aerobic synthesis of vitamin B12: ring contraction and cobalt chelation". Biochem. Soc. Trans. 33 (Pt 4): 815–9. doi:10.1042/BST0330815. PMID 16042605.
- Roessner CA, Huang KX, Warren MJ, Raux E, Scott AI (June 2002). "Isolation and characterization of 14 additional genes specifying the anaerobic biosynthesis of cobalamin (vitamin B12) in Propionibacterium freudenreichii (P. shermanii)". Microbiology. 148 (Pt 6): 1845–53. doi:10.1099/00221287-148-6-1845. PMID 12055304.
- Moore, Simon J.; Lawrence, Andrew D.; Biedendieck, Rebekka; Deery, Evelyne; Frank, Stefanie; Howard, Mark J.; Rigby, Stephen E. J.; Warren, Martin J. (2013-09-10). "Elucidation of the anaerobic pathway for the corrin component of cobalamin (vitamin B12)". Proceedings of the National Academy of Sciences. 110 (37): 14906–14911. doi:10.1073/pnas.1308098110. ISSN 0027-8424. PMC . PMID 23922391.
- Raux E, Schubert HL, Warren MJ (December 2000). "Biosynthesis of cobalamin (vitamin B12): a bacterial conundrum". Cell. Mol. Life Sci. 57 (13–14): 1880–93. doi:10.1007/PL00000670. PMID 11215515.
- Woodson JD, Zayas CL, Escalante-Semerena JC (December 2003). "A new pathway for salvaging the coenzyme B12 precursor cobinamide in archaea requires cobinamide-phosphate synthase (CbiB) enzyme activity". J. Bacteriol. 185 (24): 7193–201. doi:10.1128/jb.185.24.7193-7201.2003. PMC . PMID 14645280.
- Roth JR, Lawrence JG, Bobik TA (1996). "Cobalamin (coenzyme B12): synthesis and biological significance". Annu. Rev. Microbiol. 50: 137–81. doi:10.1146/annurev.micro.50.1.137. PMID 8905078.
- Fodje MN, Hansson A, Hansson M, Olsen JG, Gough S, Willows RD, Al-Karadaghi S (August 2001). "Interplay between an AAA module and an integrin I domain may regulate the function of magnesium chelatase". J. Mol. Biol. 311 (1): 111–22. doi:10.1006/jmbi.2001.4834. PMID 11469861.
- Maggio-Hall LA, Escalante-Semerena JC (October 1999). "In vitro synthesis of the nucleotide loop of cobalamin by Salmonella typhimurium enzymes". Proc. Natl. Acad. Sci. U.S.A. 96 (21): 11798–803. doi:10.1073/pnas.96.21.11798. PMC . PMID 10518530.
- Maggio-Hall LA, Claas KR, Escalante-Semerena JC (May 2004). "The last step in coenzyme B(12) synthesis is localized to the cell membrane in bacteria and archaea". Microbiology. 150 (Pt 5): 1385–95. doi:10.1099/mic.0.26952-0. PMID 15133100.
- Thompson TB, Thomas MG, Escalante-Semerena JC, Rayment I (May 1998). "Three-dimensional structure of adenosylcobinamide kinase/adenosylcobinamide phosphate guanylyltransferase from Salmonella typhimurium determined to 2.3 A resolution,". Biochemistry. 37 (21): 7686–95. doi:10.1021/bi973178f. PMID 9601028.
- Hashimoto Y, Nishiyama M, Horinouchi S, Beppu T (October 1994). "Nitrile hydratase gene from Rhodococcus sp. N-774 requirement for its downstream region for efficient expression". Biosci. Biotechnol. Biochem. 58 (10): 1859–65. doi:10.1271/bbb.58.1859. PMID 7765511.
- Zambelli B, Musiani F, Savini M, Tucker P, Ciurli S (March 2007). "Biochemical studies on Mycobacterium tuberculosis UreG and comparative modeling reveal structural and functional conservation among the bacterial UreG family". Biochemistry. 46 (11): 3171–82. doi:10.1021/bi6024676. PMID 17309280.
- Pollich M, Klug G (August 1995). "Identification and sequence analysis of genes involved in late steps in cobalamin (vitamin B12) synthesis in Rhodobacter capsulatus". J. Bacteriol. 177 (15): 4481–7. PMC . PMID 7635831.
- Roth JR, Lawrence JG, Rubenfield M, Kieffer-Higgins S, Church GM (June 1993). "Characterization of the cobalamin (vitamin B12) biosynthetic genes of Salmonella typhimurium". J. Bacteriol. 175 (11): 3303–16. PMC . PMID 8501034.
- Roessner CA, Williams HJ, Scott AI (April 2005). "Genetically engineered production of 1-desmethylcobyrinic acid, 1-desmethylcobyrinic acid a,c-diamide, and cobyrinic acid a,c-diamide in Escherichia coli implies a role for CbiD in C-1 methylation in the anaerobic pathway to cobalamin". J. Biol. Chem. 280 (17): 16748–53. doi:10.1074/jbc.M501805200. PMID 15741157.
- Raux E, Lanois A, Warren MJ, Rambach A, Thermes C (October 1998). "Cobalamin (vitamin B12) biosynthesis: identification and characterization of a Bacillus megaterium cobI operon". Biochem. J. 335 (1): 159–66. PMC . PMID 9742225.
- Scott AI, Roessner CA (August 2002). "Biosynthesis of cobalamin (vitamin B(12))". Biochem. Soc. Trans. 30 (4): 613–20. doi:10.1042/bst0300613. PMID 12196148.
- Kajiwara Y, Santander PJ, Roessner CA, Pérez LM, Scott AI (August 2006). "Genetically engineered synthesis and structural characterization of cobalt-precorrin 5A and -5B, two new intermediates on the anaerobic pathway to vitamin B12: definition of the roles of the CbiF and CbiG enzymes". J. Am. Chem. Soc. 128 (30): 9971–8. doi:10.1021/ja062940a. PMID 16866557.
- Kim W, Major TA, Whitman WB (December 2005). "Role of the precorrin 6-X reductase gene in cobamide biosynthesis in Methanococcus maripaludis". Archaea. 1 (6): 375–84. doi:10.1155/2005/903614. PMC . PMID 16243778.
- Shearer N, Hinsley AP, Van Spanning RJ, Spiro S (November 1999). "Anaerobic growth of Paracoccus denitrificans requires cobalamin: characterization of cobK and cobJ genes". J. Bacteriol. 181 (22): 6907–13. PMC . PMID 10559155.
- Roth, J. R.; Lawrence, J. G.; Rubenfield, M.; Kieffer-Higgins, S.; Church, G. M. (1993). "Characterization of the cobalamin (vitamin B12) biosynthetic genes of Salmonella typhimurium". Journal of Bacteriology. 175 (11): 3303–3316. PMC . PMID 8501034.
- Yin J, Xu LX, Cherney MM, Raux-Deery E, Bindley AA, Savchenko A, Walker JR, Cuff ME, Warren MJ, James MN (March 2006). "Crystal structure of the vitamin B12 biosynthetic cobaltochelatase, CbiXS, from Archaeoglobus fulgidus". J. Struct. Funct. Genomics. 7 (1): 37–50. doi:10.1007/s10969-006-9008-x. PMID 16835730.
- Brindley AA, Raux E, Leech HK, Schubert HL, Warren MJ (June 2003). "A story of chelatase evolution: identification and characterization of a small 13-15-kDa "ancestral" cobaltochelatase (CbiXS) in the archaea". J. Biol. Chem. 278 (25): 22388–95. doi:10.1074/jbc.M302468200. PMID 12686546.
- Woodson JD, Escalante-Semerena JC (March 2004). "CbiZ, an amidohydrolase enzyme required for salvaging the coenzyme B12 precursor cobinamide in archaea". Proc. Natl. Acad. Sci. U.S.A. 101 (10): 3591–6. doi:10.1073/pnas.0305939101. PMC . PMID 14990804.
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.
Precorrin-6x reductase CbiJ/CobK Provide feedback
This family consists of Precorrin-6x reductase EC:18.104.22.168. This enzyme catalyses the reaction: precorrin-6Y + NADP(+) <=> precorrin-6X + NADPH. CbiJ and CobK both catalyse the reduction of macocycle in the colbalmin biosynthesis pathway [1,2].
Raux E, Lanois A, Warren MJ, Rambach A, Thermes C; , Biochem J 1998;335:159-166.: Cobalamin (vitamin B12) biosynthesis: identification and characterization of a Bacillus megaterium cobI operon. PUBMED:9742225 EPMC:9742225
Roth JR, Lawrence JG, Rubenfield M, Kieffer-Higgins S, Church GM; , J Bacteriol 1993;175:3303-3316.: Characterization of the cobalamin (vitamin B12) biosynthetic genes of Salmonella typhimurium. PUBMED:8501034 EPMC:8501034
Internal database links
|SCOOP:||ATP-synt Epimerase NAD_binding_10 Sacchrp_dh_NADP|
This tab holds annotation information from the InterPro database.
InterPro entry IPR003723
Cobalamins (vitamin B12), both as deoxyadenosylcobalamin and methylcobalamin, are involved as cofactors in a variety of enzymatic reactions and are synthesized by some bacteria and archaea. About thirty enzymes are required to manufacture cobalamins, some of the most complex nonpolymeric molecules biosynthesized in the cell. Cobalamin biosynthesis can be divided into three distinct sections. The first results in the synthesis of the corrin ring component, cobinamide, from the ubiquitous tetrapyrrole primogenitor uroporphyrinogen III by a series of reactions including eight S-adenosyl-L- methionine-dependent methylations, ring contraction, cobalt chelation, decarboxylation, amidations, and 1-amino-2-propanol attachment. The second results in the synthesis of the lower axial ligand, dimethylbenzimidazole (DMB) and the third results in the assembly of the final coenzyme from the attachment of the corrin ring to the DMB as well as the addition of the upper coordinating ligand for the cobalt, either an adenosyl or a methyl group [PUBMED:11215515].
The precorrin-6x reductase (EC) proteins cobK and cbiJ are involved in part I of the cobalamin biosynthesis pathway. They catalyses the NADPH-dependent reduction of precorrin-6x to a dihydro derivative named precorrin-6y [PUBMED:1732193, PUBMED:10559155].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||precorrin-6A reductase activity (GO:0016994)|
|Biological process||cobalamin biosynthetic process (GO:0009236)|
|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 204 members:2-Hacid_dh_C 3Beta_HSD 3HCDH_N 3HCDH_RFF adh_short adh_short_C2 ADH_zinc_N ADH_zinc_N_2 AdoHcyase_NAD AdoMet_MTase AlaDh_PNT_C Amino_oxidase ApbA AviRa B12-binding Bac_GDH Bin3 Bmt2 CbiJ CheR CMAS CmcI CoA_binding CoA_binding_2 CoA_binding_3 Cons_hypoth95 DAO DapB_N DFP DNA_methylase DOT1 DRE2_N DREV DUF1188 DUF1442 DUF1611_N DUF166 DUF1776 DUF2431 DUF268 DUF2855 DUF3410 DUF364 DUF43 DUF5129 DUF5130 DUF938 DXP_reductoisom DXPR_C 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 G6PD_N GCD14 GDI GDP_Man_Dehyd GFO_IDH_MocA GIDA GidB GLF Glu_dehyd_C Glyco_hydro_4 Glyco_tran_WecB GMC_oxred_N Gp_dh_N GRAS GRDA HI0933_like HIM1 IlvN ISPD_C K_oxygenase KR LCM Ldh_1_N LpxI_N Lycopene_cycl Malic_M Mannitol_dh MCRA Met_10 Methyltr_RsmB-F Methyltr_RsmF_N Methyltrans_Mon Methyltrans_SAM Methyltransf_10 Methyltransf_11 Methyltransf_12 Methyltransf_14 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_28 Methyltransf_29 Methyltransf_3 Methyltransf_30 Methyltransf_31 Methyltransf_32 Methyltransf_33 Methyltransf_34 Methyltransf_4 Methyltransf_5 Methyltransf_7 Methyltransf_8 Methyltransf_9 Methyltransf_PK MethyltransfD12 MetW Mg-por_mtran_C MOLO1 Mqo MT-A70 MTS Mur_ligase N2227 N6-adenineMlase N6_Mtase N6_N4_Mtase NAD_binding_10 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 NSP11 NSP16 OCD_Mu_crystall Orbi_VP4 PALP PARP_regulatory PCMT PDH PglD_N Polysacc_syn_2C Polysacc_synt_2 Pox_MCEL Pox_mRNA-cap Prenylcys_lyase PrmA PRMT5 Pyr_redox Pyr_redox_2 Pyr_redox_3 Reovirus_L2 RmlD_sub_bind Rossmann-like rRNA_methylase RrnaAD Rsm22 RsmJ Sacchrp_dh_NADP SAM_MT SE Semialdhyde_dh Shikimate_DH Spermine_synth TehB THF_DHG_CYH_C Thi4 ThiF TPM_phosphatase TPMT TrkA_N TRM TRM13 TrmK tRNA_U5-meth_tr Trp_halogenase TylF Ubie_methyltran UDPG_MGDP_dh_N UPF0020 UPF0146 Urocanase 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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the UniProtKB sequence database using the family HMM
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- a Java applet developed at the University of Dundee. You will need Java installed before running jalview
- an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
- an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.
You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.
You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.
We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
If you find these logos useful in your own work, please consider citing the following article:
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
|Author:||Bashton M , Bateman A|
|Number in seed:||347|
|Number in full:||2646|
|Average length of the domain:||238.40 aa|
|Average identity of full alignment:||32 %|
|Average coverage of the sequence by the domain:||85.21 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||14|
|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 CbiJ domain has been found. There are 3 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...