SII-SWORD/CoKE huggingface dataset:
Colanic acid biosynthesis, glycosyl transferase, WcaL (Colanic_acid_synth_WcaL)
Type: Family

This entry represents one of the glycosyl transferases involved in the biosynthesis of colanic acid, an exopolysaccharide expressed in Enterobacteraceae species .
4Fe4S-binding SPASM domain (4Fe4S-binding_SPASM_dom)
Type: Domain

This domain contains regions binding additional 4Fe4S clusters found in various radical SAM proteins C-terminal to the domain described by

. Radical SAM enzymes with this domain tend to be involved in protein modification, including anaerobic sulphatase maturation proteins, a quinohemoprotein amine dehydrogenase biogenesis protein, the Pep1357-cyclizing
radical SAM enzyme, and various bacteriocin biosynthesis proteins . SkfB from
Bacillus subtilis
, which catalyses the formation of the thioether bond required for production of the sporulation killing factor SkfA , also contains this domain. The motif CxxCxxxxxCxxxC is nearly invariant for members of this family, although PqqE has a variant form. This domain has been named SPASM for Subtilosin, PQQ, Anaerobic Sulphatase, and Mycofactocin.
Quinohemoprotein amine dehydrogenase, gamma subunit maturation protein (QH-AmDH_gsu_maturation)
Type: Family

Members of this protein family are radical SAM enzymes responsible for post-translational modifications to the gamma subunit of quinohemoprotein amine dehydrogenases. It has been suggested that this protein is responsible for intrapeptidyl thioether cross-linking rather than cysteine tryptophylquinone biogenesis in the gamma subunit .
Quinohemoprotein amine dehydrogenase, alpha subunit (QH-AmDH_asu)
Type: Family

Quinohemoprotein amine dehydrogenases (QHNDH)

) are enzymes produced in the periplasmic space of certain Gram-negative bacteria, such as Paracoccus denitrificans and Pseudomonas putida, in response to primary amines, including n-butylamine and benzylamine. QHNDH catalyses the oxidative deamination of a wide range of aliphatic and aromatic amines through formation of a Schiff-base intermediate involving one of the quinone O atoms . Catalysis requires the presence of a novel redox cofactor, cysteine tryptophylquinone (CTQ). CTQ is derived from the post-translational modification of specific residues, which involves the oxidation of the indole ring of a tryptophan residue to form tryptophylquinone, followed by covalent cross-linking with a cysteine residue . There is one CTQ per subunit in QHNDH. In addition to CTQ, two haem c cofactors are present in QHNDH that mediate the transfer of the substrate-derived electrons from CTQ to an external electron acceptor, cytochrome c-550 .

QHNDH is a heterotrimer of alpha, beta and gamma subunits. The alpha and beta subunits contain signal peptides necessary for the translocation of QHNDH to the periplasm. The alpha subunit is composed of four domains - domain 1 forming a dihaem cytochrome, and domains 2-4 forming antiparallel β-barrel structures; the beta subunit is a 7-bladed β-propeller that provides part of the active site; and the small, catalytic gamma subunit contains the novel cross-linked CTQ cofactor, in addition to additional thioester cross-links between Cys and Asp/Glu residues that encage CTQ. The gamma subunit assumes a globular secondary structure with two short α-helices having many turns and bends .

This entry represents the QHNDH alpha subunit.
Sporulation delaying protein C-like (SdpC-like)
Type: Family

This entry represents the antimicrobial Sporulation delaying protein C from Bacillus subtilis (SdpC) and related proteins in species as distant as Myxococcus xanthus from the Deltaproteobacteria . SdpC collapses the proton motive force (probably both the membrane potential and pH gradient) across the cell membrane, which leads to autolysis, probably forming a proton channel . Its maturation is dependent on SdpA and SdpB .
TOMM system kinase/cyclase fusion protein (TOMM_kin_cyc)
Type: Family

This entry represents a family of proteins of around 1350 in length. They are found in multiple species of Burkholderia, in Acidovorax avenae subsp. citrulli AAC00-1 and Delftia acidovorans SPH-1, and in multiple copies in Sorangium cellulosum, in genomic neighbourhoods that include a cyclodehydratase/docking scaffold fusion protein and a member of the thiazole/oxazole modified metabolite (TOMM) precursor family. The proteins have a kinase domain in their N-terminal 300 amino acids, followed by a cyclase homology domain, followed by regions without named domain definitions. They are probable bacteriocin-like metabolite biosynthesis proteins.
Pyrrolysine biosynthesis protein PylC (Pyrrolys_PylC)
Type: Family

This entry represents PylC, which is part of a three-gene cassette that directs the biosynthesis of pyrrolysine, the twenty-second amino acid, that is incorporated in some species at a UAG canonical stop codon . The radical S-adenosyl-L-methionine (SAM) protein PylB mediates a lysine mutase reaction that produces 3-methylornithine, which is then ligated to a second molecule of lysine by PylC before oxidation by PylD results in pyrrolysine .
Pyrrolysine biosynthesis protein PylB (Pyrrolys_PylB)
Type: Family

This entry represents PylB, which is part of a three-gene cassette that directs the biosynthesis of pyrrolysine, the twenty-second amino acid, that is incorporated in some species at a UAG canonical stop codon . PylB possesses signature residues suggesting it to be a radical SAM protein, which mediate radical-catalysed reactions. It catalyses the isomerisation of L-lysine to (2R,3R)-3-methylornithine .
Cyclic nucleotide-binding domain protein (cNMP-bd)
Type: Family

Members of this protein family are uncharacterised and contain two copies of the cyclic nucleotide-binding domain. Members are restricted to select cyanobacteria but are found regularly in association with a transport operon that, in turn, is associated with the production of putative bacteriocins. This suggests a possible role as a bacteriocin-type transport-associated protein.
His-Xaa-Ser system-associated, MauG-like protein (MauG-like)
Type: Family

This entry represents a protein family with homology to the MauG methylamine utilisation protein (

). MauG is required to complete the maturation of the tryptophan tryptophylquinone (TTQ) cofactor in the methylamine dehydrogenase light (beta) chain. It occurs regularly with proteins of the His-Xaa-Ser system, which contains peptide-modifying radical SAM enzymes. Not all instances of the His-Xaa-Ser system include this protein .
Sporulation delaying protein SdpB (Sporulation_SdpB)
Type: Family

This entry represents SdpB, an integral membrane protein associated with production of the cannibalism peptide SdpC in Bacillus subtilis , and related proteins. Similar proteins are found in Myxococcus xanthus.
Thiazolylpeptide-type bacteriocin precursor (Thiopep_bacteriocin_prcur)
Type: Family

Members of this protein family are the precursors of a family of small bacteriocins (i.e. microcins) with thiopeptide type modifications, a highly modified subclass of heterocycle-containing peptide antibiotics. Members tend to be found clustered in genomes with proteins recognised by

and proteins/domains annotated as lantibiotic dehydratase (

,

), and with a cyclodehydratase/docking protein fusion protein characteristic of heterocycle formation. Members with known function block translation by inhibiting translation factor activity .
D-alanyl-lipoteichoic acid biosynthesis DltD, Firmicutes (LTA_DltD)
Type: Family

DltD is part of the DltABCD system which is widely distributed in the Firmicutes for D-alanylation of lipoteichoic acids (LTA). The most common form of LTA, as in Staphylococcus aureus, has a backbone of polyglycerolphosphate .
Spore photoproduct lyase, firmicutes (SPL_firmicutes)
Type: Family

This entry represents a family of Spore photoproduct lyase (SPL) proteins from firmicutes.

Bacterial spores are remarkable in their resistance to chemical and physical stresses, including exposure to UV radiation. The unusual UV resistance of bacterial spores is a result of the unique photochemistry of spore DNA coupled with the efficient repair of accumulated damage. Exposure of bacterial spores to UV radiation results in the formation of a methylene-bridged thymine dimer, 5-thyminyl-5,6-dihydrothymine, a spore photoproduct, or SP, as the primary photoproduct. SP accumulates in UV-irradiated spores, however it is rapidly repaired upon germination, thus giving rise to the extraordinary UV resistance of bacterial spores. The repair of SP is catalyzed by the enzyme spore photoproduct lyase (SPL), and involves the direct reversal of SP to two thymines without base excision .
Putative exported peptide YydF-like (YydF-like)
Type: Family

This entry describes a rare family of small proteins, about 50 residues in length, that includes YydF from Bacillus subtilis and SAG 2028 from Streptococcus agalactiae 2603V/R. Mutational analysis and genomic context show that members of this family likely are modified by a (variably present) radical SAM enzyme, are exported by an ABC transporter, and may have antimicrobial or signalling properties (or both). The member from Bacillus subtilis induces the LiaRS two-component system .
Nitrile hydratase alpha subunit /Thiocyanate hydrolase gamma subunit (CN_Hdrtase_asu/SCN_Hdrlase_gsu)
Type: Family

Nitrile hydratases (

) are bacterial enzymes that catalyse the hydration of nitrile compounds to the corresponding amides. They are used as biocatalysts in acrylamide production, one of the few commercial scale bioprocesses, as well as in environmental remediation for the removal of nitriles from waste streams. Nitrile hydratases are composed of two subunits, alpha and beta, and are normally active as a tetramer, α(2)β(2). Nitrile hydratases contain either a non-haem iron or a non-corrinoid cobalt centre, both types sharing a highly conserved peptide sequence in the alpha subunit (CXLCSC) that provides all the residues involved in coordinating the metal ion. Each type of nitrile hydratase specifically incorporated its metal with the help of activator proteins encoded by flanking regions of the nitrile hydratase genes that are necessary for metal insertion. The Fe-containing enzyme is photo-regulated: in the dark the enzyme is inactivated due to the association of nitric oxide (NO) to the iron, while in the light the enzyme is active by photo-dissociation of NO. The NO is held in place by a claw setting formed through specific oxygen atoms in two modified cysteines and a serine residue in the active site . The cobalt-containing enzyme is unaffected by NO, but was shown to undergo a similar effect with carbon monoxide . Fe-and cobalt-containing enzymes also display different inhibition patterns with nitrophenols.

Thiocyanate hydrolase (SCNase) is a cobalt-containing metalloenzyme with a cysteine-sulphinic acid ligand that hydrolyses thiocyanate to carbonyl sulphide and ammonia .

The two enzymes, nitrile hydratase and SCNase, are homologous over regions corresponding to almost the entire coding regions of the genes: the beta and alpha subunits of thiocyanate hydrolase were homologous to the amino-and carboxyl-terminal halves of the beta subunit of nitrile hydratase, and the gamma subunit of thiocyanate hydrolase was homologous to the alpha subunit of nitrile hydratase .
Thiocyanate hydrolase, gamma subunit (Thiocyan_Hydrolase_gsu)
Type: Family

Members of this family are the gamma subunit of thiocyanate hydrolase. This family is closely related to the nitrile hydratase, alpha subunit (

).
Sporulation delaying protein SdpA (Sporulation_SdpA)
Type: Family

This entry represents SdpA and similar proteins that are found in Myxococcus xanthus, Stigmatella aurantiaca DW4/3-1, Streptomyces sp. ACTE, etc. SdpA is associated with production and export of the cannibalism peptide SdpC in Bacillus subtilis .
Cyclised secreted peptide (Cyclised_pep)
Type: Family

Members of this family are short secreted precursor peptides, in which the mature form undergoes a cyclisation between a Lys and a Trp four residues away . The modification enzyme appears to be an adjacent encoded radical SAM protein. Genomes encoding this system include Streptococcus thermophilus LMD-9 and Lactococcus lactis subsp. cremoris MG1363, among others.
Peptide radical SAM maturase , YydG (Pep_rSAM_mat_YydG)
Type: Family

Members of this radical SAM protein family for peptide modification occur only in the context of members of family

, which average about 50 amino acids in length. In Bacillus subtilis, this protein (YydG) appears to act on its cognate target peptide (YydF) prior to its export, and result in the creation of a signaling molecule that induces the LiaRS two-component system .
Acetyldiaminopimelate deacetylase (AcetylDAP_deacetylase)
Type: Family

Two lysine biosynthesis pathways evolved separately in organisms, the diaminopimelic acid (DAP) and aminoadipic acid (AAA) pathways. The DAP pathway synthesizes L-lysine from aspartate and pyruvate, and diaminopimelic acid is an intermediate. This pathway is utilised by most bacteria, some archaea, some fungi, some algae, and plants. The AAA pathway synthesizes L-lysine from alpha-ketoglutarate and acetyl coenzyme A (acetyl-CoA), and alpha-aminoadipic acid is an intermediate. This pathway is utilised by most fungi, some algae, the bacterium Thermus thermophilus, and probably some archaea, such as Sulfolobus, Thermoproteus, and Pyrococcus. No organism is known to possess both pathways .

There four known variations of the DAP pathway in bacteria: the succinylase, acetylase, aminotransferase, and dehydrogenase pathways. These pathways share the steps converting L-aspartate to L-2,3,4,5- tetrahydrodipicolinate (THDPA), but the subsequent steps leading to the production of meso-diaminopimelate, the immediate precursor of L-lysine, are different .

The succinylase pathway acylates THDPA with succinyl-CoA to generate N-succinyl-LL-2-amino-6-ketopimelate and forms meso-DAP by subsequent transamination, desuccinylation, and epimerization. This pathway is utilised by proteobacteria and many firmicutes and actinobacteria.

The acetylase pathway is analogous to the succinylase pathway but uses N-acetyl intermediates. This pathway is limited to certain Bacillus species, in which the corresponding genes have not been identified.

The aminotransferase pathway converts THDPA directly to LL-DAP by diaminopimelate aminotransferase (DapL) without acylation. This pathway is shared by cyanobacteria, Chlamydia, the archaeon Methanothermobacter thermautotrophicus, and the plant Arabidopsis thaliana.

The dehydrogenase pathway forms meso-DAP directly from THDPA, NADPH, and NH4 _ by using diaminopimelate dehydrogenase (Ddh). This pathway is utilised by some Bacillus and Brevibacterium species and Corynebacterium glutamicum.

Most bacteria use only one of the four variants, although certain bacteria, such as C. glutamicum and Bacillus macerans, possess both the succinylase and dehydrogenase pathways.

This entry represents acetyldiaminopimelate deacetylase, which converts N-acetyl-L-2-amino-6-diaminopimelate to L,L-DAP. It is the last step of the lysine biosynthesis acetylase pathway.
Radical SAM target protein, putative (rSAM_target_put)
Type: Family

Members of this family of small proteins, approximately 100 amino acids in length, lack of homology to any known enzymes. Family members possess a distinctive C-terminal region motif, with the common modification target residue Cys flanked by sterically permissive Gly residues. They co-occur with a subfamily of radical SAM proteins in several species of Halobacteria and Bacillus. Since the radical SAM proteins belong to a branch in which most characterised members act on peptide substrates, it possible that this family is a radical SAM target.
Non-F420 flavinoid oxidoreductase (Non-F420_Flavin_OxRdtase)
Type: Family

This entry represents a family of oxidoreductases from species that lack F420 biosynthesis. It is suggested that members of this family bind FMN, FO, or a novel flavinoid cofactor, but not F420 per se.
xxxLxxG heptad repeat (xxxLxxG_rpt)
Type: Repeat

This entry represents a repeat of seven residues each, in which the fourth residue tends to be Leu and the seventh tends to be Gly in each set. This heptad periodicity, corresponding to two turns of an α helix, suggests α-helical structure. Arrangement of these sequences on a helical wheel would show a strict alternation of Leu and Gly residues on one side of the helix, that is, an extremely bulky side chain alternating with the virtual absence of one. This suggests an extended zippering of one α helix to another, analogous to the shorter leucine zippers found in many dimerizing transcription factors. Proteins in which these heptad repeats occur often have higher order repeats of a unit comprised of several heptads.
F420-dependent oxidoreductase, NP1902A (F420_NP1902A)
Type: Family

This family of luciferase-like monooxygenases is restricted to the order Halobacteriales. SIMBAL analysis suggests this oxidoreductase binds coenzyme F420 rather than flavin mononucleotide .
Colanic acid biosynthesis, glycosyl transferase, WcaI (Colanic_acid_synth_WcaI)
Type: Family

This entry represents WcaI, one of the glycosyl transferases involved in the biosynthesis of colanic acid, an exopolysaccharide expressed in Enterobacteraceae species .
MSMEG_0567/sll0787, C-terminal domain (MSMEG_0567/sll0787_C)
Type: Domain

This entry includes the C-terminal domain of MSMEG_0567 from Mycobacterium smegmatis. Members of this entry are found broadly in Cyanobacteria, Proteobacteria, Actinobacteria and has been linked to a nitrogen starvation response in some of those species.
Putative glycyl-radical enzyme activating enzyme YjjW (YjjW_bact)
Type: Family

Members of this family are radical SAM enzymes, designated YjjW in E. coli, that are paired with and appear to activate a glycyl radical enzyme of unknown function, designated YjjI. This activase and its target are found in Clostridial species as well as E. coli and cousins. Members of this family may be misannotated as pyruvate formate lyase activating enzyme .
Mycofactocin maturase MftC (MftC)
Type: Family

Mycofactocin maturase MftC is a radical S-adenosylmethionine (SAM) enzyme responsible for the first step of the biosynthesis of the enzyme cofactor mycofactocin (MFT). It catalyzes two reactions at the C terminus of the mycofactocin precursor (the MftA peptide): the first one is the oxidative decarboxylation of the C-terminal L-tyrosine of MftA, forming an unsaturated tyramine moiety ; the second reaction is the cross-linking of the tyramine with the penultimate L-valine residue, forming a five-membered lactam ring . Its activity requires the presence of the MftB chaperone and it is also required for alcohol metabolism in Mycobacteria .
Pyrrolysine biosynthesis protein PylD (Pyrrolys_PylD)
Type: Family

This entry represents PylD, which is part of a three-gene cassette that directs the biosynthesis of pyrrolysine, the twenty-second amino acid, that is incorporated in some species at a UAG canonical stop codon .
UDP-GlcNAc diphosphorylase/GlcNAc-1-P N-acetyltransferase, GlmU, archaeal-type (Bifunctiontional_GlmU_arc-type)
Type: Family

The MJ_1101 protein from Methanococcus jannaschii has been characterised as the GlmU, a bifunctional enzyme (UDP-N-acetylglucosamine diphosphorylase/glucosamine-1-phosphate N-acetyltransferase) catalyzing the final two steps of UDP-GlcNAc biosynthesis. GlmU is responsible for the acetylation of GlcN-1-P to GlcNAc-1-P, and for the uridyl transfer from UTP to GlcNAc-1-P, to produce UDP-GlcNAc and pyrophosphate. It also catalyses the reverse reaction, i.e. the cleavage of UDP-GlcNAc with pyrophosphate to form UTP and GlcNAc-1-P. To a lesser extent, is also able to use dUTP or dTTP as the nucleotide substrate, but not CTP, ATP or GTP .

Many of the proteins identified by this entry originate from genes in proximity to the glmS and glmM genes and are also presumed to be GlmU. However, some archaeal genomes contain multiple closely-related homologues from this family and it is not clear what the substrate specificity is for each of them.

This entry also contains the bifunctional sugar-1-phosphate nucleotidylyltransferase/acetyltransferase. This enzyme is involved in the synthesis of UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylgalactosamine (UDP-GalNAc) .
Colanic acid biosynthesis, glycosyl transferase, WcaC (Colanic_acid_synth_WcaC)
Type: Family

This is one of the glycosyl transferases involved in the biosynthesis of colanic acid, an exopolysaccharide expressed in Enterobacteraceae species .
UDP-GlcNAc diphosphorylase/GlcNAc-1-P N-acetyltransferase, GlmU, bacterial-type (Bifunctiontional_GlmU_bac-type)
Type: Family

The MJ_1101 protein from Methanococcus jannaschii has been characterised as the GlmU, a bifunctional enzyme (UDP-N-acetylglucosamine diphosphorylase/glucosamine-1-phosphate N-acetyltransferase) catalyzing the final two steps of UDP-GlcNAc biosynthesis . Homologues of this enzyme are identified in a number of bacterial organisms. A number of these are observed in proximity to the glmS and glmM genes, and phylogenetic profiling identifies the LEPBI_I0518 gene in Leptospira biflexa as a likely Glm-system candidate. There are significant structural differences between these bacterial homologues with their archaeal counterparts represented by

.
Colanic acid biosynthesis, pyruvyl transferase, WcaK (Colanic_acid_synth_WcaK)
Type: Family

Pyruvyl transferase is involved in the biosynthesis of colanic acid, an exopolysaccharide expressed in Enterobacteraceae species .
Nitrilase (Nitrilase)
Type: Family

This family represents a subfamily of a C-N bond-cleaving hydrolases (see

) that includes nitrilase from Burkholderia phymatum. It catalyses the hydrolysis of a broad range of nitriles to yield their corresponding carboxylic acid and ammonia . The preferred substrate is trans-cinnamonitrile, followed by mono/di-cyanopyridines and aromatic substituted nitriles, with a moderate activity toward 3-phenylpropionitrile . It shows weak activity toward some aliphatic nitriles, including adiponitrile and glutaronitrile, and the arylacetonitrile 2-thiopheneacetonitrile .
Alcohol dehydrogenase, zinc-type, actinomycetes (ADH_Zn_actinomycetes)
Type: Family

This entry describes a group of zinc-binding dehydrogenases, including some characterised as alcohol dehydrogenase B, that occur only in species that contain the very small protein mycofactocin

, a possible cofactor precursor, and radical SAM protein

.
Sulphate-starvation-induced SfnB (S04_starv_induced_SfnB)
Type: Family

Members of this protein family belong to the greater family of acyl-CoA dehydrogenases. This family includes the sulphate starvation induced protein SfnB of Pseudomonas putida strain DS1, which is both encoded nearby to and phylogenetically closely correlated with the dimethyl sulphone monooxygenase SfnG. This family shows considerable sequence similarity to the Rhodococcus dibenzothiophene desulphurisation enzyme DszC, although that enzyme falls outside of the scope of this family.
Alkylhydroperoxidase domain-containing protein, Avi7169 (AhpD_Avi7169)
Type: Family

This entry represents alkylhydroperoxidase-related proteins. Most of these proteins contain the alkylhydroperoxidase core domain (AhpD).
2,3-diaminopropionate biosynthesis protein SbnA (SbnA)
Type: Family

Members of this family include SbnA, a protein of the staphyloferrin B biosynthesis operon of Staphylococcus aureus. SbnA and SbnB together appear to synthesize 2,3-diaminopropionate, a precursor of certain siderophores and other secondary metabolites. SbnA uses PLP and substrates O-phospho-L-serine and L-glutamate to produce a metabolite N-(1-amino-1-carboxyl-2-ethyl)-glutamic acid (ACEGA), while SbnB uses NAD(+) to oxidatively hydrolyze ACEGA to yield alpha-ketoglutarate and L-Dap .
His-Xaa-Ser rich protein HxsA-like (HxsA-like)
Type: Family

Members of this uncharacterised protein family share a histidine/serine-rich cluster, typically H-R-S-H-S-S-H-R-S-H-S-S-H. Members are found always in the context of a pair of radical SAM proteins, HxsB and HxsC, and a fourth protein HxsD. The system is predicted to perform peptide modifications, likely in the His-Xaa-Ser region, to produce some uncharacterised natural product .