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59  structures 5907  species 0  interactions 20032  sequences 184  architectures

Family: CbiA (PF01656)

Summary: CobQ/CobB/MinD/ParA nucleotide binding domain

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This is the Wikipedia entry entitled "Cobalamin biosynthesis". More...

Cobalamin biosynthesis Edit Wikipedia article

Methylcobalamin, another biologically active form. The dark red crystals dissolve in water giving cherry-colored solutions.

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.[1] In certain mammals, cobalamin is obtained through the diet, and is required for methionine synthase and methylmalonyl-CoA mutase.[2] In humans, it plays essential roles in folate metabolism and in the synthesis of the citric acid cycle intermediate, succinyl-CoA.[3]

Overview of cobalamin biosynthesis

There are at least two distinct cobalamin biosynthetic pathways in bacteria:[4]

Biosynthetic pathways to Vitamin B12 from aminolevulinic acid (ALA) in bacteria and archaea[5]
Vitamin B12 (as cyano cobalamin) and its parent cobyric acid

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.[11][12][5]
  • 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.[5][13]

A further type of synthesis occurs through a salvage pathway, where outside corrinoids are absorbed to make B12.[5] 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.[14][15]

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.[7][16][17]

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 Rhône-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.[18][19]

From uroporphyrinogen III to precorrin-2

The enzyme CobA catalyses the two chemical reactions EC[20]

precorrin-2 product of the two methylation reactions
(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

The enzyme CobI catalyzes the reaction EC[18]

precorrin-2 + S-adenosyl methionine precorrin-3A + S-adenosyl-L-homocysteine

From precorrin-3A to precorrin-3B

The enzyme CobG catalyzes the reaction EC[18]

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 γ-lactone ring formed from the ring A acetic acid sidechain closing back on to the macrocycle.

From precorrin-3B to precorrin-4

The enzyme CobJ continues the theme of methyl group insertion by catalysing the reaction EC[18]

precorrin-3B + S-adenosyl methionine precorrin-4 + S-adenosyl-L-homocysteine
The conversion of precorrin-3B to precorrin-4 is catalysed by the enzyme CobJ in Pseudomonas denitrificans

Importantly, during this step the macrocycle ring-contracts so that the product contains for the first time the corrin core which characterises cobalamin.

From precorrin-4 to precorrin-5

Methyl group insertions continue when the enzyme CobM catalyses the reaction EC[21]

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

The enzyme CobF catalyzes the reaction EC[21]

precorrin-5 + S-adenosyl methionine + H2O precorrin-6A + S-adenosyl-L-homocysteine + acetate
The conversion of precorrin-5 to precorrin-6A is catalysed by the enzyme CobF in Pseudomonas denitrificans

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

The enzyme CobK now reduces a double bond in ring D by catalysing the reaction EC[21]

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[21]

precorrin-6B + 2 S-adenosyl methionine precorrin-8X + 2 S-adenosyl-L-homocysteine + CO2
The conversion of precorrin-6B to precorrin-8 is catalysed by the enzyme CobL in Pseudomonas denitrificans

From precorrin-8 to hydrogenobyrinic acid

The enzyme CobH catalyzes a rearrangement reaction EC[22]

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

The next enzyme in the pathway, CobB, converts two of the eight carboxylic acid groups into their primary amides in the reaction EC[23]

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

Cobalt(II) insertion into the macrocycle is catalysed by the enzyme Cobalt chelatase (CobNST) in the reaction EC[24]

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.[10][25]

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.[26] The reactions are catalysed by CysG EC and Sirohydrochlorin cobaltochelatase EC[27]

From cobalt-sirohydrochlorin to cobalt-factor III

As in the aerobic pathway, the third methyl group is introduced by a methyltransferase enzyme, CbiL in the reaction EC[26]

cobalt-sirohydrochlorin + S-adenosyl methionine cobalt-factor III + S-adenosyl-L-homocysteine

From cobalt-factor III to cobalt-precorrin-4

Methylation and ring contraction to form the corrin macrocycle occurs next EC, catalysed by the enzyme Cobalt-factor III methyltransferase (CbiH)[28]

cobalt-factor III + S-adenosyl methionine cobalt-precorrin-4 + S-adenosyl-L-homocysteine
The conversion of cobalt-factor III to cobalt-precorrin-4 is catalysed by the enzyme CbiH

In this pathway, the resulting material has contains a δ-lactone, a six-membered ring, rather than the γ-lactone (five-membered ring) of precorrin-3B.

From cobalt-precorrin-4 to cobalt-precorrin-5A

The introduction of the methyl group at C-11 in the next step is catalysed by Cobalt-precorrin-4 methyltransferase (CbiF) in the reaction EC[29]

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[29]

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;[30] Cobalt-precorrin-6A reductase (CbiJ / EC;[31] Cobalt-precorrin-7 (C15)-methyltransferase (decarboxylating) (CbiET / EC, Cobalt-precorrin-8 methylmutase (CbiC / EC and CbiA / EC The final enzyme forms cob(II)yrinic acid a,c-diamide as the two pathways converge.[5]

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 and then the enzyme Cob(I)yrinic acid a,c-diamide adenosyltransferase (CobO) attaches an adenosyl ligand to the metal in reaction EC Next, the enzyme CobQ (reaction EC converts all the carboxylic acids, except the propionic acid on ring D, to their primary amides.[7][21]

From adenosylcobyric acid to adenosylcobinamide phosphate

In aerobic organisms, the enzyme CobCD (reaction EC now attaches (R)-1-amino-2-propanol (derived from threonine) to the propionic acid, forming adenosylcobinamide and the enzyme CobU (reaction EC phosphorylates the terminal hydroxy group to form adenosylcobinamide phosphate.[21] 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 catalysed by the enzyme CbiB.[5]

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 and converted by CobT in reaction EC to alpha-ribazole 5' phosphate. Then the enzyme CobU (reaction EC activates adenosylcobinamide phosphate by formation of adenosylcobinamide-GDP and CobV (reaction EC 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[32][33]

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.[34] Even organisms such as Salmonella typhimurium that can make cobalamin also assimilate it from external sources when available.[5][35][36][37] Uptake into cells is facilitated by ABC transporters which absorb the cobalamin through the cell membrane.[38]

Cobalamin metabolism in humans

In humans, dietary sources of cobalamin are bound after ingestion as transcobalamins.[39] 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.[40][41][42]


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  40. ^ 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): 260–266. doi:10.1016/j.ymgme.2009.04.005. PMC 2709701. PMID 19447654.
  41. ^ Banerjee, Ruma; Gherasim, Carmen; Padovani, Dominique (2009). "The tinker, tailor, soldier in intracellular B12 trafficking". Current Opinion in Chemical Biology. 13 (4): 484–491. doi:10.1016/j.cbpa.2009.07.007. PMC 5750051. PMID 19665918.
  42. ^ Quadros, Edward V. (2010). "Advances in the understanding of cobalamin assimilation and metabolism". British Journal of Haematology. 148 (2): 195–204. doi:10.1111/j.1365-2141.2009.07937.x. PMC 2809139. PMID 19832808.

Further reading

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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.

CobQ/CobB/MinD/ParA nucleotide binding domain Provide feedback

This family consists of various cobyrinic acid a,c-diamide synthases. These include CbiA P29946 and CbiP Q05597 from S.typhimurium [4] and CobQ Q52686 from R. capsulatus [3]. 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. Vitamin B12 is an important cofactor and an essential nutrient for many plants and animals and is primarily produced by bacteria [4]. The family also contains dethiobiotin synthetases as well as the plasmid partitioning proteins of the MinD/ParA family [6].

Literature references

  1. 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

  2. Raux E, Lanois A, Rambach A, Warren MJ, Thermes C; , Biochem J 1998;335:167-173.: Cobalamin (vitamin B12) biosynthesis: functional characterization of the Bacillus megaterium cbi genes required to convert uroporphyrinogen III into cobyrinic acid a,c-diamide. PUBMED:9742226 EPMC:9742226

  3. Pollich M, Klug G; , J Bacteriol 1995;177:4481-4487.: Identification and sequence analysis of genes involved in late steps in cobalamin (vitamin B12) synthesis in Rhodobacter capsulatus. PUBMED:7635831 EPMC:7635831

  4. 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

  5. Galperin MY, Grishin NV; , Proteins 2000;41:238-247.: The synthetase domains of cobalamin biosynthesis amidotransferases cobB and cobQ belong to a new family of ATP-dependent amidoligases, related to dethiobiotin synthetase. PUBMED:10966576 EPMC:10966576

  6. Motallebi-Veshareh M, Rouch DA, Thomas CM; , Mol Microbiol 1990;4:1455-1463.: A family of ATPases involved in active partitioning of diverse bacterial plasmids. PUBMED:2149583 EPMC:2149583

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002586

This domain is found in various cobyrinic acid a,c-diamide synthases. These include CbiA ( SWISSPROT ) and CbiP ( SWISSPROT ) from S. typhimurium [ PUBMED:8501034 ], and CobQ ( SWISSPROT ) from R. capsulatus [ PUBMED:7635831 ]. 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. Vitamin B12 is an important cofactor and an essential nutrient for many plants and animals and is primarily produced by bacteria [ PUBMED:8501034 ].

The domain is also found in dethiobiotin synthetases as well as the plasmid partitioning proteins of the MinD/ParA family [ PUBMED:2149583 ].

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan P-loop_NTPase (CL0023), which has the following description:

AAA family proteins often perform chaperone-like functions that assist in the assembly, operation, or disassembly of protein complexes [2].

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...

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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.

Representative proteomes UniProt
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Representative proteomes UniProt

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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.

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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

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...


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.

Curation View help on the curation process

Seed source: Pfam-B_782 (release 4.1)
Previous IDs: CBIA;
Type: Domain
Sequence Ontology: SO:0000417
Author: Bashton M , Bateman A , Griffiths-Jones SR
Number in seed: 79
Number in full: 20032
Average length of the domain: 207.60 aa
Average identity of full alignment: 15 %
Average coverage of the sequence by the domain: 54.58 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null --hand HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.4 25.4
Trusted cut-off 25.4 25.4
Noise cut-off 25.3 25.3
Model length: 127
Family (HMM) version: 26
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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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 CbiA domain has been found. There are 59 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.

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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
A0A0R0G2V0 View 3D Structure Click here
A0L8B9 View 3D Structure Click here
A0LJ24 View 3D Structure Click here
A0QVI7 View 3D Structure Click here
A1AT17 View 3D Structure Click here
A1BFI0 View 3D Structure Click here
A1KBC7 View 3D Structure Click here
A1S3L6 View 3D Structure Click here
A1T225 View 3D Structure Click here
A1TMF3 View 3D Structure Click here
A1UEN7 View 3D Structure Click here
A1WAM6 View 3D Structure Click here
A2SI71 View 3D Structure Click here
A3CL56 View 3D Structure Click here
A4FM88 View 3D Structure Click here
A4G3R1 View 3D Structure Click here
A4G3R6 View 3D Structure Click here
A4J806 View 3D Structure Click here
A4VJ35 View 3D Structure Click here
A4VJ40 View 3D Structure Click here
A4XT53 View 3D Structure Click here
A4YXJ9 View 3D Structure Click here
A5D3N4 View 3D Structure Click here
A5GMB9 View 3D Structure Click here
A5GUP3 View 3D Structure Click here
A5VM87 View 3D Structure Click here
A6L4Y5 View 3D Structure Click here
A6TU70 View 3D Structure Click here
A6UWF6 View 3D Structure Click here
A6X034 View 3D Structure Click here
A6X051 View 3D Structure Click here
A7I9K5 View 3D Structure Click here
A7ILW0 View 3D Structure Click here
A8I5C0 View 3D Structure Click here
A8MET3 View 3D Structure Click here
A9AZZ2 View 3D Structure Click here
A9GM36 View 3D Structure Click here
A9KMP5 View 3D Structure Click here
A9WIN9 View 3D Structure Click here
B0KCS6 View 3D Structure Click here