SII-SWORD/CoKE huggingface dataset:
Di-heme enzyme MbnH-like (MbnH-like)
Type: Family

This entry represents a subfamily of di-heme proteins related to the di-heme cytochrome c peroxidase and to MauG (methylamine utilization G), an enzyme that performs a tryptophan tryptophylquinone modification to the methylamine dehydrogenase light chain. In methanobactin biosynthesis systems, MbnH introduces forms kynurenine from the first Trp in a WxW motif in MbnP (see

), required for its copper-binding activity .
Putative heme d1 biosynthesis protein, NirJ1 (NirJ1)
Type: Family

Members of this radical SAM domain-containing family, designated NirJ1, occur in genomic contexts with a paralogue NirJ2, and with other nitrite reductase operon genes associated with heme d1 biosynthesis in Heliobacillus mobilis and Heliophilum fasciatum . NirJ1 is presumed to be a heme d1 biosynthesis protein by context, and may be involved in the conversion of uroporphyrinogen III acetate groups to methyl groups.
Multidrug resistance protein MdtC (Multidrug-R_MdtC)
Type: Family

Multidrug resistance proteins are molecular pumps that participate in a low energy shock adaptive response in some bacteria. The MdtABC tripartite complex is composed of MdtA, MdtB and MdtC, and confers resistance against novobiocin and deoxycholate . The mdtABC operon is transcriptionally activated by BaeR and belongs to the AcrB/AcrD/AcrF family

This entry represents MdtC which forms a heteromultimer with MdtB.
CE1759 family FMN reductase (CE1759_FMN_reduct)
Type: Family

This entry represents a group of proteins that regularly co-occur in genomes, typically as gene pairs, with members of

, a probable FMN-dependent member of the bacterial luciferase-like monooxygenase (LLM) family. At least one member, RF|YP_001509627.1 from Frankia sp. EAN1pec, is fused to the LLM protein. The function of these gene pairs is unknown, but members in this entry are annotated as oxidoreductases and NADPH-dependent FMN reductases.
Glycoside hydrolase, family 2, beta-galactosidase (Glyco_hydro_2_beta_Galsidase)
Type: Family

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

This entry represents enzymes responsible for hydrolysis of terminal non-reducing beta-D-galactose residues in beta-D-galactosides. This group of enzymes belongs to the glycosyl hydrolase 2 family.
Luciferase-like monooxygenase, FMN-dependent, putative (LLM_FMN-dep_put)
Type: Family

This tightly conserved subfamily of the bacterial luciferase-like monooxygenase (LLM) family, with members showing more than 60 % pairwise sequence identity, includes proteins from both species with and without the ability to make coenzyme F420. Therefore, the likely cofactor is FMN rather than F420. The presence of three members in Kineococcus radiotolerans SRS30216 and two in Saccharopolyspora erythraea NRRL 2338 suggests a closely related subfamily rather than exactly conserved function.
Replication factor C, large subunit (Rep_factor-C_lsu)
Type: Family

These proteins are part of the RFC clamp loader complex, which loads the PCNA sliding clamp onto DNA. The large subunits (RfcL) form a heteromultimer with small subunits (RfcS). Proteins in this entry belong to the activator 1 small subunit family RfcL subfamily.
Probable malonic semialdehyde reductase RutE-like (RutE-like)
Type: Family

This entry represents the putative NADH dehydrogenase/NAD(P)H nitroreductase RutE family. RutE appears to be a malonic semialdehyde reductase in the Rut pathway for pyrimidine degradation .
Bis(5'-nucleosyl)-tetraphosphatase PrpE (Bis(5'-nucleosyl)-tetraP_PrpE)
Type: Family

Bis(5'-nucleosyl)-tetraphosphatase (PrpE) asymmetrically hydrolyses Ap4p to yield AMP and ATP, but does not hydrolyse Ap2a or Ap6A. It also has an ATPase activity. In Bacillus subtilis, it has been shown to dephosphorylate phosphotyrosine but not phosphoserine or phosphothreonine from phosphorylated peptides . It is also involved in spore germination by controlling expression of genes coding for GerA and GerK receptors .
HMP-PP phosphatase (HMP-PP_phosphatase)
Type: Family

HMP-PP phosphatase catalyzes the hydrolysis of 4-amino-2-methyl-5-hydroxymethylpyrimidine pyrophosphate (HMP-PP) to 4-amino-2-methyl-5-hydroxymethylpyrimidine phosphate (HMP-P) .
Cysteine desulfuration protein SufE (Cysteine_desulfuration_SufE)
Type: Family

Cysteine desulphuration protein SufE participates in cysteine desulphuration mediated by SufS. Cysteine desulphuration mobilizes sulphur from L-cysteine to yield L-alanine and constitutes an essential step in sulphur metabolism for biosynthesis of a variety of sulphur-containing biomolecules. SufE functions as a sulphur acceptor for sufS, by mediating the direct transfer of the sulphur atom from the S-sulphanylcysteine of sufS, an intermediate product of cysteine desulphuration process .
Dihydrodipicolinate reductase (DHDPR_bac)
Type: Family

Dihydrodipicolinate reductase (DHDPR), a product of an essential gene referred to as dapB, catalyzes the second step of lysine biosynthesis . It catalyses the reduction of 2,3-dihydrodipicolinate (DHDP) to 2,3,4,5-tetrahydrodipicolinate (THDP) in a nucleotide dependent reaction :

2,3-dihydrodipicolinate + NAD(P)H = 2,3,4,5-tetrahydrodipicolinate + NAD(P)(+)

Interestingly, DHDPR could also function as a dehydratase in addition to the role of a nucleotide dependent reductase .
Glutathione-regulated potassium-efflux system protein KefC (K_H_efflux_KefC)
Type: Family

The kefC gene encodes a potassium-efflux system that is regulated by glutathione metabolites . Full activation of KefC also requires a soluble regulatory protein, KefF . KefC belongs to the monovalent cation:proton antiporter 2(CPA2) transporter family TC 2.A.37 (http://www.tcdb.org/search/result.php?tc=2.A.37).
3-keto-L-gulonate-6-phosphate decarboxylase, UlaD (3-keto-L-gulonate6Pdecase_UlaD)
Type: Family

3-keto-L-gulonate 6-phosphate decarboxylase (KGPDC) (

) is encoded by the ulaD gene in Escherichia coli . The enzyme catalyses the decarboxylation of 3-keto-L-gulonate-6-phosphate into L-xylulose-5-phosphate, and may be involved in anaerobic L-ascorbate utilisation . KGPDC is a homodimer of (β/α)8-barrels, with the active sites located at the dimer interface .
Enolase-phosphatase E1 (Enolase-ppase_E1)
Type: Family

This enzyme is the enolase-phosphatase of methionine salvage, a pathway that regenerates methionine from methylthioadenosine (MTA). Adenosylmethionine (AdoMet) is a donor of different moieties for various processes, including methylation reactions. Use of AdoMet for spermidine biosynthesis, which leads to polyamine biosynthesis, leaves MTA as a by-product that must be cleared. In Bacillus subtilis and related species, this single protein is replaced by separate enzymes with enolase and phosphatase activities.

This entry also matches a number of probable bifunctional methylthioribulose-1-phosphate dehydratase/enolase-phosphatase E1 enzymes.
Anaerobic nitric oxide reductase transcription regulator (NorR)
Type: Family

These proteins are required for the expression of anaerobic nitric oxide(NO) reductase. They acts as transcriptional activators for at least the norVW operon. NorR requires activation by sigma-54 .
N-acetylmannosamine kinase, bacterial (ManNAc_kinase_bac)
Type: Family

A family of bacterial proteins has been described which groups transcriptional repressors, sugar kinases and yet uncharacterised open reading frames . This family, known as ROK (Repressor, ORF, Kinase) includes the xylose operon repressor, xylR, from Bacillus subtilis, Lactobacillus pentosus and Staphylococcus xylosus; N-acetylglucosamine repressor, nagC, from Escherichia coli; glucokinase

from Streptomyces coelicolor; fructokinase

from Pediococcus pentosaceus, Streptococcus mutans and Zymomonas mobilis; allokinase

and mlc from E. coli; and E. coli hypothetical proteins yajF and yhcI and the corresponding Haemophilus influenzae proteins. The repressor proteins (xylR and nagC) from this family possess an N-terminal region not present in the sugar kinases and which contains an helix-turn-helix DNA-binding motif.

This entry represent the bacterial N-acetylmannosamine kinase subfamily of the ROK family. Proteins in this entry catalyze the phosphorylation of N-acetylmannosamine(ManNAc) to ManNAc-6-P .
Endo-type membrane-bound lytic murein transglycosylase A (EmtA)
Type: Family

This murein-degrading enzyme may play a role in the recycling of muropeptides during cell elongation and/or cell division. It catalsyses the endolytic cleavage of the (1->4)-beta-glycosidic linkage between N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc) residues in peptidoglycan with concomitant formation of a 1,6-anhydrobond in the MurNAc residue . Enzymatic cleavage activity occurs preferentially at a distance of more than two disaccharide units from the ends of the glycan chain. The enzyme is also called peptidoglycan lytic endotransglycosylase and belongs to the transglycosylase slt family.
Glutathione-regulated potassium-efflux system ancillary protein KefG (K_H_efflux_KefG)
Type: Family

KefG is required for full activity of KefB. It is unlikely that KefG has oxido-reductase activity, it has probably evolved from its function as an oxido-reductase to be a regulator of KefB. KefG belongs to the NAD(P)H dehydrogenase (quinone) family,(KefG subfamily).
Glutathione-regulated potassium-efflux system ancillary protein KefF (K_H_efflux_KefF)
Type: Family

KefF is a stabilising subunit of the KefC K(+) efflux system . It is required for full activity of KefC. KefF has oxidoreductase activity , and probably evolved from its function as an oxido-reductase to be a regulator of KefC. KefF belongs to the NAD(P)H dehydrogenase (quinone) family.
RNA polymerase-associated protein RapA (Helicase_RapA)
Type: Family

RNA polymerase-associated protein RapA is a transcription regulator that activates transcription by stimulating RNA polymerase (RNAP) recycling . This stimulation occurs in cases of stress conditions such as supercoiled DNA or high salt concentrations. The protein probably acts by releasing the RNAP, when it is trapped or immobilized on tightly supercoiled DNA however, it does not activate transcription on linear DNA. RapA is probably not involved in DNA repair. The protein has a higher affinity for the core RNAP than for the holoenzyme and its ATPase activity is stimulated by binding to RNAP. RapA belongs to the SNF2/RAD54 helicase family and contains 1 helicase ATP-binding domain.
Flavohemoprotein (Hmp)
Type: Family

This entry represents flavohemoproteins, which have multiple enzymatic activities and consist of three distinct domains - an N-terminal heme- and oxygen-binding domain (globin domain) followed by an oxidoreductase FAD-binding domain and a NAD-binding reductase domain . They function as nitric oxide dioxygenases and a ferrisiderophore reductase whereby the complexed Fe+3 iron of siderophores are reduced to Fe+2 and released . They are involved in the inducible response to nitrosative stress, as their nitric oxide dioxygenase ability is used in aerobic NO detoxification, a reaction which utilises O2 and NAD(P)H to convert NO to nitrate and therefore offers protection from various noxious nitrogen compounds .
L-ascorbate-6-phosphate lactonase UlaG (L-ascorbate_6P_UlaG)
Type: Family

These proteins catalyse the hydrolysis of L-ascorbate-6-P into 3-keto-L-gulonate-6-P, which is essential for L-ascorbate utilization under anaerobic conditions . UlaG is a manganese-dependent l-ascorbate-6-P lactonase that catalyses the hydrolysis of L-ascorbate-6-phosphate to 3-keto-L-gulonate-6-phosphate superfamily .
Inosose dehydratase (IolE)
Type: Family

This enzyme catalyzes the dehydration of inosose (2-keto-myo-inositol, 2KMI or 2,4,6/3,5-pentahydroxycyclohexanone) to 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione (D-2,3-diketo-4-deoxy-epi-inositol) . It uses glutathione and cobalt or manganese as cofactors and belongs to the iolE/mocC family.
Heme oxygenase IsdG (IsdG)
Type: Family

IsdG is a heme-degrading components of the Isd system in Gram-positive bacteria such as S. aureus . It may function as a heme-degrading monooxygenase . It allows pathogenic bacteria to utilise host heme as an iron source and enables the release of free iron through catalysis of oxidative degradation of the heme macrocyclic porphyrin ring in the presence of a suitable electron donor such as ascorbate or NADPH--cytochrome P450 reductase. It is important for protection of bacteria against heme-mediated toxicity .
C4-dicarboxylate transport protein (C4_dicarb_transport)
Type: Family

It has been shown that integral membrane proteins that mediate the uptake of a wide variety of molecules with the concomitant uptake of sodium ions (sodium symporters) can be grouped, on the basis of sequence and functional similarities into a number of distinct families. One of these families is known as the sodium:dicarboxylate symporter family (SDF).

Such re-uptake of neurotransmitters from the synapses, is thought to be an important mechanism for terminating their action, by removing these chemicals from the synaptic cleft, and transporting them into presynaptic nerve terminals, and surrounding neuroglia. this removal is also believed to prevent them accumulating to the point of reaching neurotoxic .

The structure of these transporter proteins has been variously reported to contain from 8 to 10 transmembrane (TM) regions, although 10 now seems to be the accepted value.

This entry represents cell membrane proteins which are responsible for the transport of dicarboxylates such assuccinate, fumarate, and malate from the periplasm across the membrane . They belong to the sodium:dicarboxylate (SDF) symporter(TC 2.A.23) family.
D-tagatose-bisphosphate aldolase, class II, subunit GatY (TagBP_aldolase_GatY)
Type: Family

Escherichia coli and other enteric bacteria contain two closely related D-tagatose 1,6-bisphosphate (TagBP)-specific aldolases - KbaYZ (also known as AgaYZ) and GatYZ. Unlike other class II aldolases, which are homodimeric enzymes, KbaYZ and GatYZ are heterodimers, and are comprised of subunits KbaY/GatY and GatY/GatZ.

The KbaY/GatY subunits alone are sufficient to show aldolase activity and contain most or all of the residues that have been identified as essential for substrate/product recognition and catalysis in class II aldolases . However, subunits GatZ/KbaZ are required for full activity and for good in vivo and in vitro stability.

This entry represents the GatY catalytic subunit of the GatYZ tagatose-1,6-bisphosphate aldolase. GatYZ is responsible for catalyzing the reversible aldol condensation of dihydroxyacetone phosphate (DHAP or glycerone-phosphate) with glyceraldehyde 3-phosphate (G3P) to produce tagatose 1,6-bisphosphate (TBP) .
Acireductone dioxygenase ARD, bacteria (ARD_bac)
Type: Family

Acireductone dioxygenase catalyses 2 different reactions between oxygen and the acireductone 1,2-dihydroxy-3-keto-5-methylthiopentene (DHK-MTPene), depending upon the metal bound in the active site. Fe-containing acireductone dioxygenase (Fe-ARD or ARD') produces formate and 2-keto-4-methylthiobutyrate (KMTB), the alpha-ketoacid precursor of methionine in the methionine recycle pathway. Ni-containing acireductone dioxygenase (Ni-ARD) produces methylthiopropionate,carbon monoxide and formate, and does not lie on the methionine recycle pathway .
Anaerobic nitric oxide reductase flavorubredoxin (Anaer_NO_rdtase_flvorubredoxin)
Type: Family

This entry represents an anaerobic nitric oxide reductase, which utilises NADH to detoxify nitric oxide and therefore protects 4Fe-4S NO-sensitive enzymes .
Malate dehydrogenase, type 1, bacterial (Malate_DH_type1_bac)
Type: Family

This enzyme catalyzes the reversible oxidation of malate to oxaloacetate. It exist as a homodimer and belongs to the LDH/MDH superfamily, specifically to the MDH type 1 family.
Lipoprotein LpqB (Lipoprotein_LpqB)
Type: Family

This cell membrane protein belongs to the LpqB lipoprotein family.
Cytochrome b6-f complex iron-sulfur subunit (Cyt_b6_f_Rieske)
Type: Family

This entry represents the Rieske FeS protein (encoded by the PetC gene) of the cytochrome b6f complex from plants and cyanobacteria. The Rieske subunit acts by binding plastoquinol anion, transferring an electron to the 2Fe-2S cluster, then releasing the electron to the
cytochrome f haem iron. The 2Fe-2S cluster is bound in the highly conserved C-terminal region of the Rieske subunit. In plants, Rieske FeS is required for the successful assembly of the b6f complex and is essential for photosynthesis .

The plant cytochrome b6f is located in the thylakoid membrane and functions in both linear and cyclic electron transport, providing ATP and NADPH for photosynthetic carbon fixation. The cytochrome b6f complex has eight different subunits, six being encoded in the chloroplast genome (PetA [cyt f], PetB [cyt b6], PetD, PetG, PetL, and PetN) and two in the nucleus (PetC [Rieske FeS] and PetM. The complex functions as a dimer .
Nitric oxide reductase FlRd-NAD(+) reductase (NO_rdtase_NorW)
Type: Family

This entry represents an accessory proteins for anaerobicnitric oxide (NO) reductase. It is thought to reduce the rubredoxin moiety of NOreductase.
Probable phosphoketolase (Phosphoketolase)
Type: Family

Phosphoketolases (PK) are key enzymes of the pentose phosphate pathway of heterofermentative and facultative homofermentative lactic acid bacteria and of the D-fructose 6-phosphate shunt of bifidobacteria. PK activity has been sporadically reported in other microorganisms including eukaryotic yeasts.Proteins in this entry are probable phosphoketolases belonging to the XFP family and are thought to require thiamine pyrophosphate as a cofactor.
Methanobactin precursor, Mb-OB3b (Methanobactin_OB3b)
Type: Family

Methanobactins are siderophore-like copper-chelating natural products with considerable variety from species to species . The 11-residue methanobactin of Methylosinus trichosporium OB3b is derived from a 30-residue precursor. A very similar 31-residue precursor is found in the rice endophyte Azospirillum sp. B510, which has not yet been shown to produce a methanobactin.
Bacteriocin precursor, CLOSPO-01332, putative (Bacteriocin_CLOSPO-01332_put)
Type: Family

Members of this protein family are Cys-rich putative bacteriocin precursor peptides found in a few strains of Clostridium and Anaerococcus. This family is related to the family of CLI_3235 (

). Members of both families are found next to a CLI_3234 family radical SAM protein that appears to perform post-translational modification.
Capreomycidine synthase (Capreomycidine_synthase)
Type: Family

Members of this family are capreomycidine synthases, which perform the second of two steps in the biosynthesis of 2S,3R-capreomycidine from arginine. The best characterised member is VioD from the biosynthetic pathway for viomycin . Capreomycidine is an unusual amino acid used by non-ribosomal peptide synthases (NRPS) to make the tuberactinomycin class of peptide antibiotic.
Arginine beta-hydroxylase, Fe2/alpha-ketoglutarate-dependent (Arginine_beta-hydroxylase)
Type: Family

Members of this protein family are L-arginine beta-hydroxylase, members of a broader family of enzymes dependent on Fe(II), alpha-ketoglutarate, and molecular oxygen. Enzymes in the broader family but excluded by this model include clavaminate synthase, taurine dioxygenase, and prolyl-4-hydroxylase .
Conserved hypothetical protein CHP03996, oxidoreductase (CHP03996_oxidoreductase)
Type: Family

This protein family occurs in the vicinity of the putative mycofactocin biosynthesis operon in a number of Actinobacteria such as Frankia sp. and Rhodococcus sp. Family members contain a TIM-barrel fold commonly found in NADH:flavin oxidoreductase/NADH oxidase enzymes that use FMN/FAD as cofactor.
Bacteriocin precursor, CLI3235 family, putative (Bacteriocin_CLI3235)
Type: Family

Members of this protein family are Cys-rich putative bacteriocin precursor peptides restricted to Clostridia but found in multiple species, with up to three per genome. They are found next to a CLI_3234 family radical SAM protein that may perform post-translational modification. This model describes approximately 35 residues starting from the N terminus. Precursor peptides average about 50 amino acids in length.
Conserved hypothetical protein CHP04072, B12-binding/radical SAM-type (CHP04072_B12-bd/rSAM)
Type: Family

Members of this protein family occur in conserved genomic contexts highly suggestive of lipid biosynthesis, including an island shared between Kuenenia stuttgartiensis, which produces ladderanes , and Desulfotalea psychrophila, which produces a different kind of unusual polyunsaturated hydrocarbon.
Selenoprotein GSU1558/SbtA-like (GSU1558/StbA-like)
Type: Family

Members of this protein family are small peptides found in the vicinity of a peptide modification-type radical SAM protein family, nearly always selenopeptides. Multiple members of this protein family occur in species with a selenocysteine incorporation systems and have a TGA stop codon at position that aligns with cysteine residues from other homologues. This finding strongly suggests that GSU_1558 and similar members of the family are selenopeptides. The selenocysteine insertion sequence (SECIS) finder bSECISearch finds two homologous SECIS elements for two TGA codons in the extension of GSU_1558, and multiple members of the SbtA family of more than two selenocysteine sites . It was shown that the radical SAM enzyme SbtM removes two hydrogen atoms from sites with either Sec or Cys, creating a thio(seleno)oxazole moiety .
Conserved hypothetical protein CHP04069, acyl carrier-related (CHP04069_acyl_carrier-rel)
Type: Family

Members of this family are often related to an acyl carrier-like domain and are found in genomic contexts associated with a small Cys-rich peptide and a radical SAM protein which probably modifies the peptide.
Methanobactin biosynthesis cassette protein MbnC-like (MbnC-like)
Type: Family

This entry represents a family of proteins from proteobacteria, including Methanobactin biosynthesis cassette protein MbnC from Methylosinus trichosporium, part of the he iron-containing heterodimeric MbnBC enzyme complex, which is central to the biosynthesis of methanobactins (Mbns), copper-binding metallophores isolated from methane-oxidizing bacteria. MbnC consists of an N-terminal α-helical domain and two additional α helices packed against a four-stranded antiparallel β sheet .
His-Xaa-Ser system protein HxsD (HxsD)
Type: Family

This rare conserved hypothetical protein of small size occurs exclusively, and perhaps universally, in the context of a pair of (uncharacterised) radical SAM proteins, HxsC (

) and HxsB (

). Many members of this family have invariant motifs LYW and LLNDYxLRE, but PSI-BLAST starting from family members well below 20% pairwise sequence identity to this group eventually brings in the entire family as modeled here. The CHP03979 family (

) represents the fourth regularly conserved member of this system .
Six-cysteine peptide SCIFF (Six-Cys_pep_SCIFF)
Type: Family

Members of this protein family are essentially universal in the class Clostridia and therefore highly abundant in the human gut microbiome. This short peptide is designated SCIFF, for Six Cysteines in Forty-Five residues. It is a presumed ribosomal natural product precursor, always found associated with a yet-uncharacterised radical SAM protein, family

, that resembles other peptide modification radical SAM enzymes and is designated SCIFF radical SAM maturase . The literature originally described the thioether cross-link introduced by ScfB from a Cys side chain as going to the alpha carbon (making SCIFF a "sactipeptide") of a Met residue, but more recently is was found to go elsewhere (making it a "ranthipeptide"), to the gamma carbon of a Thr residue .