Summary: Radical SAM superfamily
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Radical SAM Edit Wikipedia article
Radical SAM proteins are members of a large superfamily of iron-sulfur cluster-containing enzymes that cleave S-Adenosyl methionine reductively to produce a 5â€²-deoxyadenosyl 5â€²-radical as an intermediate. The radical intermediate allows enzymes to perform a wide variety of unusual chemical reactions. Examples of radical SAM enzymes include spore photoproduct lyase, activases of pyruvate formate lyase and anaerobic sulfatases, lysine 2,3-aminomutase, and various enzymes of cofactor biosynthesis, peptide modification, metalloprotein cluster formation, tRNA modification, lipid metabolism, etc.
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Radical SAM superfamily Provide feedback
Radical SAM proteins catalyse diverse reactions, including unusual methylations, isomerisation, sulphur insertion, ring formation, anaerobic oxidation and protein radical formation.
Sofia HJ, Chen G, Hetzler BG, Reyes-Spindola JF, Miller NE; , Nucleic Acids Res 2001;29:1097-1106.: Radical SAM, a novel protein superfamily linking unresolved steps in familiar biosynthetic pathways with radical mechanisms: functional characterization using new analysis and information visualization methods. PUBMED:11222759 EPMC:11222759
Benjdia A, Leprince J, Guillot A, Vaudry H, Rabot S, Berteau O; , J Am Chem Soc. 2007;129:3462-3463.: Anaerobic sulfatase-maturating enzymes: radical SAM enzymes able to catalyze in vitro sulfatase post-translational modification. PUBMED:17335281 EPMC:17335281
Internal database links
|SCOOP:||DUF4917 DUF5131 Fer4 Fer4_12 Fer4_14 Fer4_16 Fer4_18 Fer4_2 Fer4_21 Fer4_4 Fer4_6 Fer4_7 Fer4_8 Fer4_9 His_biosynth LIAS_N Peptidase_M50 Radical_SAM_2 TP_methylase Wyosine_form|
|Similarity to PfamA using HHSearch:||Fer4_12 Fer4_14 Radical_SAM_2|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR007197
Radical SAM proteins are found in all three domains of life and share an unusual Fe-S cluster associated with generation of a free radical by reductive cleavage of SAM and often provide an anaerobic or oxygen-independent mechanism that is found as an aerobic reaction in other proteins. Radical SAM proteins catalyse diverse reactions, including unusual methylations, isomerization, sulphur insertion, ring formation, anaerobic oxidation and protein radical formation. These proteins function in DNA precursor, vitamin, cofactor, antibiotic and herbicide biosynthesis and in biodegradation pathways [ PUBMED:11222759 , PUBMED:15317939 ].
Radical SAM proteins share several common features, notably three strictly conserved cysteine residues generally included in the CxxxCxxC motif. These critical cysteines coordinate the unusual [4Fe-4S]2+/1+ cluster, while SAM serves as ligand for the fourth iron atom and acts as a cofactor or a cosubstrate [ PUBMED:11222759 ]. The radical SAM enzymes biochemically characterised to date have in common the cleavage of the [4Fe-4S]1+-SAM complex to [4Fe-4S]2+-Met and the 5'-deoxyadenosyl radical, which abstracts a hydrogen atom from the substrate to initiate a radical mechanism [ PUBMED:22761404 , PUBMED:18307109 ].
The Radical SAM domain is organised in a fold related to the beta-barrel or TIM barrel, in which beta-strands are arranged in a barrel-like array, with peripheral helices intervening between beta-strands. The [4Feâ4S] clusters and substrates are bound within the barrels, as is typical of TIM barrel enzymes [ PUBMED:28893989 , PUBMED:22579873 ].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||catalytic activity (GO:0003824)|
|iron-sulfur cluster binding (GO:0051536)|
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:
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This large superfamily of TIM barrel enzymes all contain a common phosphate binding site. The phosphate is found in a variety of cofactors and ligands such as FMN [1,2].
The clan contains the following 61 members:4HFCP_synth Ala_racemase_N ALAD Aldolase AP_endonuc_2 BtpA CdhD ComA CutC DAHP_synth_1 DAHP_synth_2 DeoC DHDPS DHO_dh DHquinase_I DUF2090 DUF4862 DUF561 DUF692 DUF993 Dus F_bP_aldolase FMN_dh G3P_antiterm GatZ_KbaZ-like Glu_syn_central Glu_synthase His_biosynth HMGL-like IGPS IMPDH KDGP_aldolase Lys-AminoMut_A MtrH NanE NAPRTase NeuB NMO OAM_alpha OMPdecase Orn_Arg_deC_N Oxidored_FMN PcrB PdxJ PRAI PRMT5_TIM Pterin_bind QRPTase_C Radical_SAM Radical_SAM_2 RhaA Ribul_P_3_epim SOR_SNZ TAL_FSA ThiC_Rad_SAM ThiG TIM TMP-TENI Trp_syntA UvdE UxuA
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:
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You can see the alignments as HTML or in three different sequence viewers:
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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.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
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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:||Bateman A|
|Number in seed:||491|
|Number in full:||134611|
|Average length of the domain:||169.5 aa|
|Average identity of full alignment:||14 %|
|Average coverage of the sequence by the domain:||41.73 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null --hand HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||24|
|Download:||download the raw HMM for this family|
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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 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:
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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 Radical_SAM domain has been found. There are 161 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.