SII-SWORD/CoKE huggingface dataset:
Conserved hypothetical protein CHP04031, Htur1727 (CHP04031_Htur1727)
Type: Family

Members of this protein family show homology to the putative PaaH (or PaaB) subunit of the phenylacetate-CoA oxygenase complex. However, all members are found in the Halobacteriales in the vicinity of a radical SAM protein homologous to the PqqE protein of pyroquinoline quinone (PQQ) biosynthesis. Members are well-conserved to about residue 75, but then become low-complexity and hypervariable.
Copper-binding protein MbnP-like (MbnP-like)
Type: Family

Members of this rare protein family regularly occur next to a member of the MXAN_0977 subfamily (

) of the di-heme cytochrome c peroxidase/MauG family (

). MauG itself (

) is a protein modification enzyme responsible for the tryptophan tryptophylquinone (TTQ) modification involved in methylamine dehydrogenase activation. Members of this family have motif WxW, the first Trp of which is post-translationally modified by the MauG-like protein. All members of this family have a motif of four spaced invariant Cys residues, while additional homologues outside the scope of this family lack the four Cys residues. The protein member from methanobactin producer Methylosinus trichosporium Strain OB3b (

), which is encoded just three genes away from methanobactin biosynthesis cassette protein MbnC, is designated MbnP, and is a copper-binding protein. It may be a methanobactin copper release protein .
Glucose-methanol-choline oxidoreductase, bacteria (GMC_oxidoreductase_bact)
Type: Family

This entry describes a set of dehydrogenases belonging to the glucose-methanol-choline oxidoreductase (GMC oxidoreductase) family. Members of the family are found in bacterial genome contexts containing also members of families

and

, and are proposed to be uniform in function.
Conserved hypothetical protein CHP04014, B12-binding/radical SAM-type (CHP04014_B12-bd/rSAM)
Type: Family

Members of this family, which are found in methanogenic archaea, have both a B12 binding homology domain (

) and a radical SAM domain (

). They occur only once per genome. Some species that express proteins of this family also express a related protein with a similar domain architecture (see

).
Conserved hypothetical protein CHP04013, B12-binding/radical SAM-type (CHP04013_B12-bd/rSAM)
Type: Family

Members of this family have both a B12 binding homology domain and a radical SAM domain, and occur only once per genome. Some species with members of this family have a related protein with similar domain architecture. This protein is occurs largely in archaeal methanogens but also in a few bacteria, including Thermotoga maritima and Myxococcus xanthus.
Pre-mycofactocin glycosyltransferase (MftF)
Type: Family

Pre-mycofactocin glycosyltransferase MftF is a glycosyltransferase that catalyses the oligoglycosylation of pre-mycofactocin (PMFT), adding up to nine beta-1,4-linked glucose residues . It is involved in the biosynthesis of the enzyme cofactor mycofactocin (MFT), a redox cofactor which belongs to the family of ribosomally synthesized and post-translationally modified peptides (RiPPs) and is involved in alcohol metabolism of mycobacteria including Mycobacterium tuberculosis .
Conserved hypothetical protein CHP04029, CMD-like (CHP04029_CMD-like)
Type: Family

Sequences in this family occur as the N-terminal domain of a fusion protein with a C-terminal peroxidase-like protein, or as discrete proteins encoded next to a peroxidase-like protein. The two partners regularly are encoded near to, and in the same genomes as, a putative FMN-dependent luciferase-like monooxygenase (LLM) (

), and an ABC transporter in which

models the substrate-binding protein.
DNA sulphur modification system-associated protein 4 (DNA_S_mod_dnd_assoc_4)
Type: Family

A DNA sulphur modification system, dnd (degradation during electrophoresis), is sparsely and sporadically distributed among the bacteria. Members of this protein family are strictly limited to species with the dnd operon, and are found close to the dnd operon on the chromosomes of species such as Nostoc sp. PCC 7120, Geobacter uraniireducens Rf4, and Roseobacter denitrificans OCh 114.
Ribosomal peptide maturation radical SAM protein 1 (rSAM_ocin_1)
Type: Family

Members of this family of peptide-modifying radical SAM proteins include BstC, BstF, and BstJ, three enzymes involved in the biosynthesis of the antibiotic bottromycin D from a ribosomally translated peptide precursor that lacks a leader peptide. They appear to perform methylations of carbon atoms . Other members of the family occur in genomic contexts with RiPP family precursors in the Nif11-like and NHLP families, as well as other peptide maturases from the lanthionine synthase and cyclodehydratase families .
Mycofactocin-dependent oxidoreductase (SDR_subfam_1)
Type: Family

Members of this protein subfamily are putative oxidoreductases belonging to the larger SDR family. All members occur in genomes that encode a cassette for the biosynthesis of mycofactocin, a proposed electron carrier of a novel redox pool. Characterised members of this family are described as NDMA-dependent, meaning that a blue aniline dye serving as an artificial electron acceptor is required for members of this family to cycle in vitro, since the bound NAD residue is not exchangeable .
Glycosyltransferase, putative, MSMEG0565 family (GlycosylTfrase_MSMEG0565)
Type: Family

A conserved gene cluster found sporadically from Actinobacteria to Proteobacteria to Cyanobacteria features a radical SAM protein, an N-acetyltransferase, an oxidoreductase, and two additional proteins whose functional classes are unclear. The metabolic role of the cluster is probably biosynthetic. This glycosyltransferase, named from member MSMEG_0565 from Mycobacterium smegmatis, occurs in most but not all instances of the cluster.
Conserved hypothetical protein CHP03977, oxidoreductase (CHP03977_oxidoreductase)
Type: Family

This protein family occurs in the vicinity of the the putative mycofactocin biosynthesis operon in a number of Actinobacteria such as Frankia sp. and Rhodococcus sp., in Pelotomaculum thermopropionicum SI (Firmicutes), and in Geobacter uraniireducens Rf4 (Deltaproteobacteria). Family members contain a TIM-barrel fold commonly found in NADH:flavin oxidoreductase/NADH oxidase enzymes that use FMN/FAD as cofactor.
Mycofactocin precursor peptide (MftA)
Type: Family

Mycofactocin precursor peptide MftA is the precursor peptide that leads to mycofactocin (MFT), a redox cofactor which belongs to the family of ribosomally synthesized and post-translationally modified peptides (RiPPs) and is involved in alcohol metabolism of mycobacteria including Mycobacterium tuberculosis . MftA suffers extensive post-translational modifications by enzymes encoded by adjacent genes, namely mftB, mftC, mftD, mftE, and mftF .
Pre-mycofactocin synthase (MftD)
Type: Family

Pre-mycofactocin synthase MftD is involved in the biosynthesis of the enzyme cofactor mycofactocin (MFT), a ribosomally synthesized and post-translationally modified (RiPP) redox cofactor, and catalyses the oxidative deamination of AHDP (3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethyl-2-pyrrolidin-2-one), forming an alpha-keto amide moiety on the resulting molecule, which is called pre-mycofactocin (PMFT) . The alpha-keto amide moiety is the redox-active centre for the redox activity of mycofactocin .
Butyryl-CoA:acetate CoA-transferase (Butryl-CoA_acetate_CoA_Tfrase)
Type: Family

This enzyme represents one of at least two mechanisms for reclaiming CoA from butyryl-CoA at the end of butyrate biosynthesis (an important process performed by some colonic bacteria), namely transfer of CoA to acetate . An alternate mechanism transfers the butyrate onto inorganic phosphate, after which butyrate kinase transfers the phosphate onto ADP, creating ATP.

This entry also includes butyrate CoA-transferase from Syntrophomonas wolfei, involved in the syntrophic growth of this organism on butyrate in cooperation with methanogens or an appropriate hydrogen-scavenging bacterium .
Bacteriocin, class IIb, lactobin A/cerein 7B family (Bacteriocin_IIb_lactobn/cerein)
Type: Family

Members of this protein family are described variably as bacteriocins per se, one chain of a two-chain bacteriocin, or bacteriocin enhancer proteins. All members of the seed alignment occur in paired gene contexts with another member of the same protein family. This family includes bacteriocins that appear not to undergo post-translational modification, other than cleavage at a Gly-Gly motif coupled to sec-independent export. For many members, the N-terminal bacteriocin cleavage motif region is recognised by

. C-terminal to the cleavage motif, these proteins are hydrophobic and low in complexity, consistent with pore-forming activity as a mechanism of bacteriocin action.
Pre-heme d1 synthase NirJ (HemeD1_Synth_NirJ)
Type: Family

Heme D1 occurs in the cytochrome Cd1 subunit of nitrite reductase in species such as Pseudomonas stutzeri. NirJ is a radical SAM protein that contains two iron-sulfur clusters. It catalyzes the removal of two propionate side chains during heme D1 biosynthesis . In a number of species, distinct genes NirJ1 and NirJ2 are found in similar genomic regions; this entry describes NirJ from genomes with NirJ only.
S-adenosyl-L-methionine-dependent tRNA 4-demethylwyosine synthase, archaea (TYW1_archaea)
Type: Family

Members of this protein family are the archaeal protein TYW1 , a radical SAM protein that catalyzes the second step in creating the wye-bases, wyosine and derivatives such as wybutosine, for tRNA base modification .
[NiFe]-hydrogenase assembly, chaperone, HybE (NiFe-hyd_HybE)
Type: Family

Members of this family are chaperones for the assembly of [NiFe] hydrogenases, in the family of HybE, which is specific for hydrogenase-2 of Escherichia coli. Members often have an additional N-terminal rubredoxin domain .
Oxygen-independent coproporphyrinogen-III oxidase-like protein HemZ (HemZ)
Type: Family

Members of this radical SAM protein family are HemZ, a protein involved in coproporphyrinogen III decarboxylation. Alternative names for this enzyme (EC

) include coproporphyrinogen dehydrogenase and oxygen-independent coproporphyrinogen III oxidase. The family is related to, but distinct from HemN, and in Bacillus subtilis was shown to be connected to peroxide stress and catalase formation .
TonB-dependent outer membrane protein, SusC/RagA (TonB-dep_OMP_SusC/RagA)
Type: Family

This entry describes a clade of TonB-linked outer membrane proteins (OMP). Members of the family are restricted to the Bacteriodetes lineage (except for Gemmatimonas aurantiaca T-27 from the novel phylum Gemmatimonadetes) and occur in high copy numbers, with over 100 members from Bacteroides thetaiotaomicron VPI-5482 alone. Published descriptions of members of the family are available for RagA from Porphyromonas gingivalis , SusC from Bacteroides thetaiotaomicron , and OmpW from Bacteroides caccae . Members form pairs with members of the SusD/RagB family (

). Transporter complexes including these outer membrane proteins are likely to import large degradation products of proteins (e.g. RagA) or carbohydrates (e.g. SusC) as nutrients, rather than siderophores.
TonB-dependent outer membrane protein SusC/RagA, conserved site (TonB-dep_OMP_SusC/RagA_CS)
Type: Conserved_site

This entry describes a short conserved site found in the SusC/RagA family of outer membrane proteins from the Bacteriodetes. While many TonB-dependent outer membrane receptors are associated with siderophore import, this family seems to include generalized nutrient receptors that may convey fairly large oligomers of protein or carbohydrate. The family occurs in high copy numbers in the most abundant species of the human gut microbiome.
Ferric aerobactin reductase IutB-like (FCR-like)
Type: Family

Members of this protein family are 2Fe-2S cluster binding proteins, found regularly in the context of siderophore transporters, including Ferric aerobactin reductase IutB from Vibrio vulnificus (FCR) . Members are distantly related to FhuF from E. coli, a ferric iron reductase linked to removal of iron from hydroxamate-type siderophores .
Formate transporter FocA (Formate_transptr_FocA)
Type: Family

FocA (formate channel A) forms a pentameric formate-selective channel through the plasma membrane, involved in the bidirectional transport of formate during mixed-acid fermentation . It functions to maintain relatively constant intracellular formate levels during growth, using different mechanisms for efflux and uptake of the anion . The focA gene is largely restricted to Proteobacteria. FocA switches its mode of operation from a passive export channel at high external pH to a secondary active formate/H(+) importer at low pH . FocA is homologous to a nitrite transport protein, NirC.
Conserved hypothetical protein CHP04046, FMN-dependent (CHP04046_FMN-dependent)
Type: Family

Members of this protein family belong to a conserved seven-gene biosynthetic cluster found sparsely in Cyanobacteria, Proteobacteria, and Actinobacteria. Distant homologies to characterised proteins suggest that members are enzymes dependent on a flavinoid cofactor.
Cysteine-rich peptide, radical SAM maturase, CcpM (Cys-rich_pep_rSAM_mat_CcpM)
Type: Family

Members of this family are radical SAM enzymes that occur next to clostridial Cys-rich predicted bacteriocin (or other class of ribosomal natural product) precursors (see families

and

). They include a TIGR04085 C-terminal additional 4Fe4S cluster-binding domain that is associated with peptide modification by radical SAM enzymes, and they are proposed to be ribosomal natural product maturases. The gene symbol ccpM is assigned, for Clostridial Cys-rich Peptide Maturase .
Formate/nitrite transporter, conserved site (For/NO2_transpt_CS)
Type: Conserved_site

A number of bacterial and archaebacterial proteins involved in transporting formate or nitrite have been shown to be related :

FocA and FocB, from Escherichia coli, transporters involved in the bidirectional transport of formate .

FdhC, from Methanobacterium formicicum and Methanothermobacter thermautotrophicus (Methanobacterium thermoformicicum), a probable formate transporter.

NirC, from E. coli and Salmonella typhimurium, a probable nitrite transporter.

Bacillus subtilis hypothetical protein YrhG.

B. subtilis hypothetical protein YwcJ (ipa-48R).

The 70 kd yeast hypothetical protein YHL008c is highly similar, in its N-terminal section, to the prokaryotic members of this family.
Putative luciferase-like monooxygenase, KPN01858 (Luciferase-like_KPN01858)
Type: Family

This protein family consists of luciferase-like monooxygenases (LLM), and include KPN_01858 from Klebsiella pneumoniae as a representative member. Most are from species that lack F420 biosynthesis, so the family is likely to bind FMN as its cofactor. This family is closely associated with a binding protein-dependent ABC transporter, suggesting a role in catabolism.
PEP-CTERM/XrtA system glycosyltransferase (PEP-CTERM/XrtA_GlycosylTrfase)
Type: Family

PEP-CTERM/exosortase is a protein-sorting system associated with exopolysaccharide production. Members of this protein family are group 1 glycosyltransferases (see

) in which the overwhelming majority occur in species with the EpsH1 form of exosortase (see

), and usually co-clustered with the exosortase .
Colanic acid biosynthesis, acetyltransferase, WcaF (Colanic_acid_synth_WcaF)
Type: Family

This acetyltransferase is believed to catalyze the addition of the acetyl group that is attached through an O linkage to the first fucosyl residue of the colanic acid repetitive unit (E unit) .
Alternate signal-mediated exported protein, actinobacteria (Alt_signal_exp_actinobact)
Type: Family

Members of this Actinobacterial protein family contain the signal peptide domain

, for the variant SipW form of the signal peptidase I family. The remainder of this protein, however, differs from families such as Peptidase_M73 (

) and YqxM (

) that share the same signal peptide domain. The two known targets for export by the SipW signal peptidase in Bacillus subtilis act in producing biofilm matrix material, but the function for this Actinobacterial family is not known.
[FeFe]-hydrogenase maturation HydG, radical SAM (FeFe-hyd_mat_HydG)
Type: Family

This entry describes the radical SAM protein HydG. It is part of an enzyme metallocentre maturation system, working together with GTP-binding protein HydF and another radical SAM enzyme, HydE, in H-cluster maturation in [FeFe] hydrogenases.
BsaA-like SipW-dependent biofilm matrix protein (BsaA)
Type: Family

Members of this largely Clostridial protein family contain the signal peptide, for the variant SipW form of the signal peptidase I family. The remainder of this protein, however, differs from families such as Peptidase_M73 (

) and YqxM that share the same signal peptide domain. The two known targets for export by the SipW signal peptidase in Bacillus subtilis act in producing biofilm matrix material, but the function for the proteins in this entry is not known.

Members of this Clostridial family include BsaA from Clostridium perfringens that was recently shown to be a matrix protein of extracellular polymeric substance .
Colanic acid biosynthesis, glycosyl transferase, WcaA (Colanic_acid_synth_WcaA)
Type: Family

This entry represents WcaA, which is one of the glycosyl transferases involved in the biosynthesis of colanic acid (CA) - an exopolysaccharide expressed in Enterobacteraceae species .
Colanic acid biosynthesis, glycosyl transferase, WcaE (Colanic_acid_synth_WcaE)
Type: Family

This entry represents the putative glycosyl transferase gene product of wcaE, which is thought to be involved in the biosynthesis of colanic acid, an exopolysaccharide expressed in Enterobacteraceae species .
Natural product biosynthesis luciferase-like monooxygenase domain (Biosynth_lucif-like_mOase_dom)
Type: Domain

This entry describes a type of bacterial luciferase-like monooxygenase (LLM) domain that regularly occurs within large non-ribosomal protein synthases/polyketide synthases, as well as smaller proteins. Luciferase-like monooxygenases include members that bind either FMN or F420. FMN is the more likely binding partner in the case of proteins containing this particular domain, since many are from species that lack F420 biosynthesis capability.

This domain covers the whole length of the protein in many members of this group, including the monooxygenase MupA from Pseudomonas fluorescens (

) and Siderophore biosynthesis protein from Agrobacterium fabrum (

).
DNA phosphorothioation system restriction enzyme, putative (Dnd_restrict_put)
Type: Family

The DNA phosphorothioate modification system dnd (DNA instability during electrophoresis) recently has been shown to provide a modification essential to a restriction system. This protein family was detected by Partial Phylogenetic Profiling as linked to dnd, and its members usually are clustered with the dndABCDE genes.
Colanic acid biosynthesis, colanic acid polymerase, WcaD (Colanic_acid_synth_WcaD)
Type: Family

This entry represents a membrane protein which functions as the colanic acid repeating unit polymerase (in an analogous fashion to wzy proteins in O-antigen polymerisation) .
FMNH(2)-dependent dimethylsulfone monooxygenase SfnG (DMSO2_SphG)
Type: Family

This family of FMNH2-dependent members of the luciferase-like monooxygenase (LLM) family includes SfnG, a monooxygenase that converts dimethylsulphone (DMSO2) to methanesulphonate . This step can be followed immediately by methanesulphonate sulphonatase (an alkanesulphonate monooxygenase - see

) for the FMNH2-dependent conversion an inorganic form.
Pyridoxamine 5'-phosphate oxidase, probable FMN-dependent, Alr4036-like (Pyridox_Oxase_FMN-dep_Alr4036)
Type: Family

Pyridoxamine 5'-phosphate oxidase (

) is an enzyme that is involved in the de novo synthesis of pyridoxine (vitamin B6) and pyridoxal phosphate. It oxidizes pyridoxamine-5-P (PMP) and pyridoxine-5-P (PNP) to pyridoxal-5-P. The enzyme requires the presence of flavin mononucleotide (FMN) as a cofactor, although there is some evidence that coenzyme F420 may perform this role in some species .

The sequences of the enzyme from bacterial (genes pdxH or fprA) and fungal (gene PDX3) sources show that this protein has been highly conserved throughout evolution. PdxH is evolutionary related to one of the enzymes in the phenazine biosynthesis protein pathway, phzD (also known as phzG) .

This entry represents a subfamily that is widespread in Cyanobacteria and plants, and is named for alr4036 from Nostoc sp. PCC 7120 (

). The family consists mostly of proteins from species that lack the capability to synthesise F420, so it is probable that all members bind FMN rather than F420.
Conserved hypothetical protein CHP04064, radical SAM (CHP04064_rSAM)
Type: Family

Members of this family are radical SAM enzymes that occur co-clustered with Nif11-related bacteriocin precursors, as described by TIGRFAMs model

. They could be involved a Nif11-class bacteriocin maturation.
Petide cyclisation enzyme, radical SAM (Pep_cycl_rSAM)
Type: Family

Members of this family are radical SAM enzymes that appear to perform a cyclisation on an adjacent peptide from family

. Genomes with the complete system include Streptococcus thermophilus LMD-9 and Lactococcus lactis subsp. cremoris MG1363, among others.
Conserved hypothetical protein CHP04083, radical SAM (CHP04083_rSAM)
Type: Family

Members of this family are radical SAM enzymes, homologous to a variety of other peptide-modifying radical SAM, and found primarily in methanogenic archaea.
Conserved hypothetical protein CHP04096 (CHP04096)
Type: Family

Members of this protein family show distant local sequence similarity to a number of S-adenosyl-methionine-dependent methyltransferases. The family is identified by Partial Phylogenetic Profiling as closely tied to the DNA phosphorothioation system (dnd), and members are found adjacent to dnd genes in at least 13 species (Streptomyces lividans TK24, Shewanella frigidimarina NCIMB 400, Mycobacterium abscessus ATCC 19977, Nostoc punctiforme PCC 73102, Vibrio fischeri MJ11, etc.). The DNA phosphorothioation enables a novel form of restriction enzyme activity. Most members of this family appear in species with the DNA phosphorothioation system.
Anti sigma-R factor, mycothiol system,RsrA (Anit_sigma_mycothiol_RsrA)
Type: Family

Members of this family are the anti-sigma-R factor RsrA, which contains a CXXC motif as a thiol-disulphide redox switch. It interacts with sigma-R. It regulates and is regulated by the mycothiol system, which occurs in many actinomycetes .
[FeFe]-hydrogenase maturation HydE, radical SAM (FeFe-hyd_HydE_rSAM)
Type: Family

This entry describes the radical SAM protein HydE, one of a pair of radical SAM proteins, along with GTP-binding protein HydF, for maturation of [FeFe]-hydrogenase in Chlamydomonas reinhardtii and numerous bacteria .
Transcription regulator HTH, surface antigen (Tscrpt_reg_HTH_surface_antigen)
Type: Family

This protein is found adjacent to various classes of repetitive or low-complexity YSIRK proteins (whether unique in genome or not), in a range of species (Enterococcus faecalis X98, Ruminococcus torques, Coprobacillus sp. D7, Lysinibacillus fusiformis ZC1, Streptococcus equi subsp. equi 4047, etc). The affliated YSIRK proteins include Streptococcal protective antigen (see ) and proteins with the Rib/alpha/Esp surface antigen repeat (see

). The last quarter of this protein has an AraC family helix-turn-helix (HTH) transcriptional regulator domain.
His-Xaa-Ser system radical SAM maturase HxsB (rSAM_paired_HxsB)
Type: Family

This entry describes HxsB, one of a pair of uncharacterised radical SAM proteins, regularly found in the context of a small protein with four or more repeats of the tripeptide His-Xaa-Ser (HXS). This enzyme may be be part of a peptide modification system.