SII-SWORD/CoKE huggingface dataset:
EccCb-like, Actinobacteria (EccCb-like_Actinobacteria)
Type: Family

This entry represents the EccCb subunit of the type VII secretion system from Actinobacteria. In many proteins it forms the C-terminal domain being fused to EccCa as the N-terminal domain. Type VII secretion is defined more broadly as including secretion systems for ESAT-6-like proteins in the Firmicutes as well as in the Actinobacteria , but this family does not show close homologues in the Firmicutes.
Type VII secretion system EsaA (T7SS_EsaA)
Type: Domain

Members of this family are associated with type VII secretion systems. EsaA from Staphylococcus aureus is encoded within a cluster comprised of eight predicted ORFs (esxA, esaA, essA, esaB, essB, essC, esxY, and esxB) . Its function is unknown, though it is probably involved, with EsxA and EsxB, in the establishment of infection in the host. It is not necessary for the production and secretion of EsxA or EsxB . Some members of this family, such as YueB from Bacillus subtilis, seem to act as membrane receptors for bacteriophage SPP1 .

In some proteins this entry represents the conserved N-terminal domain.
Firmicutes EssC, C-terminal (Firmicutes_EssC_C)
Type: Domain

This entry describes the C-terminal domain of the type VII secretion protein EssC from Firmicutes. EssC contains the FtsK domains and is typically between 107 and 121 amino acids in length. It is required for secretion of EsxA and EsxB. It is related to the FtsK/SpoIIIE proteins (

), which are DNA transporters responsible for translocating missegregated chromosomes after the completion of cell division .
Type VII secretion system Rv3446c (T7SS_Rv3446c)
Type: Family

Members of this protein family occur as part of the ESX-4 cluster of type VII secretion system (T7SS) proteins in Mycobacterium tuberculosis and in similar T7SS clusters in other Actinobacteria genera, including Corynebacterium, Nocardia, Rhodococcus, and Saccharopolyspora.
Bacillithiol biosynthesis deacetylase BshB2 (BshB2)
Type: Family

Bacillithiol (BSH) is a low-molecular-weight thiol, an analog of glutathione and mycothiol, that is found largely in the Firmicutes. BSH biosynthesis requires the presence of deacetylase BshB1 or BshB2 (also termed YpjG and YojG, respectively) . This entry represents BshB2.
Bacillithiol biosynthesis deacetylase, BshB1 (Bacillithiol_biosynth_BshB1)
Type: Family

Bacillithiol (BSH) is a low-molecular-weight thiol, an analog of glutathione and mycothiol, that is found largely in the Firmicutes. BSH biosynthesis requires the presence of the deacetylases BshB1 or BshB2 (also termed YpjG and YojG, respectively) . This entry represents BshB1, which catalyzes the second step of the pathway, the deacetylation of N-acetylglucosaminylmalate (GlcNAc-Mal) to glucosamine malate (GlcN-Mal) .
CRISPR-associated protein Cas1, cyanobacteria-type (CRISPR-assoc_Cas1_cyanobact)
Type: Family

This entry describes a type of Cas1 proteins found mainly in cyanobacteria and some archaeal species, including Methanospirillum hungatei CRISPR-associated endonuclease Cas1 4.

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.
CRISPR-associated protein Cas1, MYXAN subtype (CRISPR-assoc_Cas1_MYXAN)
Type: Family

This entry represents the MYXAN subtype of the Cas1 endonuclease. Species with this type of CRISPR system include Myxococcus xanthus, Cyanothece sp., Leptospira interrogans, Sorangium cellulosum, and Anabaena variabilis ATCC 29413. The entry also detects Cas4/Cas1 fusion proteins.

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.
Domain of unknown function DUF3817, transmembrane (DUF3817_TM)
Type: Domain

This domain is associated with, strictly bacterial integral membrane proteins. It occurs in proteins that on rare occasions are fused to transporter domains such as the major facilitator superfamily domain. Of three invariant residues, two occur as a His-Gly dipeptide in the middle of three predicted transmembrane helices.
Conserved hypothetical protein CHP04042, MSMEG0570 (CHP04042_MSMEG0570)
Type: Family

This entry represents small proteins of about 90 residues long that have no detectable homologues outside this family. These proteins serve as markers for an eight-gene region whose overall function is unknown. One member of the cluster is a radical SAM protein with some similarity to enzymes of cofactor biosynthesis, another a glycosyltransferase, several represent hydrolases or oxidoreductases, and several unknown proteins.
MSMEG_0572 family nitrogen starvation response protein (MSMEG0572)
Type: Family

This entry describes a family of proteins with remote similarity to the DsrE/DsrF-like family (see

). All members are found in a context of at least seven genes that includes a radical SAM protein, suggesting biosynthesis. The system is sparsely but broadly distributed in bacteria, including Actinobacteria, Proteobacteria, and Cyanobacteria.
TasA anchoring/assembly protein (TasA)
Type: Family

This entry represents a group of bacterial proteins, including TasA from Bacillus subtilis. Microbes construct architecturally complex and ordered communities called biofilms through production of an extracellular matrix composed of an exopolysaccharide and the amyloid-like protein TasA . TasA has the propensity to polymerize into fibres enriched in β sheets and highly resistant to degradation or denaturation . TasA fibres are used by B. subtilis to build a network that connects cells and may organize the rest of the components of the extracellular matrix .
TQXA domain (TQXA_dom)
Type: Domain

This entry describes a domain of about 40 residues with an invariant TQ dipeptide in an almost invariant TQxA[VI]W motif. This domain occurs in surface-expressed proteins of Gram-positive bacteria, many of which are anchored by LPXTG-containing sortase target domains. Proteins in this entry may also have the Cna protein B-type domain and fibronectin-binding protein signal sequence. The Q in the motif becomes part of an unusual Cys-Gln thioester crosslink .
Peptide chaperone MftB (MftB)
Type: Family

Peptide chaperone MftB is a peptide chaperone involved in the biosynthesis of the enzyme cofactor mycofactocin (MFT). MFT belongs to the class of ribosomally synthesized and posttranslationally modified peptides conserved in many Actinobacteria. MftB binds MftA and MftC with high affinity, and is essential for MftC activity on MftA, likely via the formation of a ternary complex . In M.smegmatis it is also required for in vivo ethanol assimilation .
Transcriptional regulator, TetR-type (Tscrpt_reg_TetR-type)
Type: Family

Members of this family are transcriptional regulators belonging to the TetR-family. They occur in genome contexts near members of family

.
Metalloproteinase lipoprotein, BF0631 (Metalloproteinase_lipop_BF0631)
Type: Family

Members of this protein family are predicted to be zinc-dependent metalloproteinases, related to ulilysin and other members of the pappalysin family. They are found in the genera Bacteriodes and Prevotella. They are predicted to occur as lipoproteins.
Poly-beta-1,6 N-acetyl-D-glucosamine synthase PgaC/IcaA (PGA_PgaC/IcaA)
Type: Family

This entry contains bacterial poly-beta-1,6 N-acetyl-D-glucosamine synthases. This enzyme catalyzes the polymerisation of single monomer units of UDP-N-acetylglucosamine to produce the linear homopolymer poly-beta-1,6-N-acetyl-D-glucosamine (PNAG, also referred to as PIA), a biofilm adhesin polysaccharide . One named member is IcaA (intercellular adhesin protein A) from Staphylococcus epidermis. The homologous member in Escherichia coli is designated PgaC.
Poly-beta-1,6-N-acetyl-D-glucosamine N-deacetylase PgaB (PGA_deacetylase_PgaB)
Type: Family

Two well-characterised systems produce polysaccharide based on N-acetyl-D-glucosamine in straight chains with beta-1,6 linkages. These are encoded by the icaADBC operon in Staphylococcus species and the pgaABCD operon in Gram-negative bacteria such as E. coli. Both systems include a putative polysaccharide deacetylase. The PgaB protein, described in this entry, contains an additional domain lacking from its Gram-positive counterpart IcaB (

).

PgaB catalyses the N-deacetylation of poly-beta-1,6-N-acetyl-D-glucosamine, a biofilm adhesion polysaccharide .
Bacilliredoxin reductase Bdr (Bdr)
Type: Family

Bacillithiol (BSH) is a low-molecular-weight thiol, an analog of glutathione and mycothiol, that is found largely in the Firmicutes.

Included in this family is Bdr (also known as YpdA) from Bacillus subtilis, a NADPH-dependent bacilliredoxin reductase, which debacillithiolates (removes BSH) the S-bacillithiolated BrxB (BrxB-SSB), and to a lesser extent BrxC (BrxC-SSB) . It is involved in a redox cascade increasing the efficacy of BrxB function by reducing BrxB-SSB and thus reactivating it.
Radical S-adenosyl methionine enzyme HcgA-like (HcgA-like)
Type: Family

This protein family includes HcgA from Methanococcus maripaludis (MMP0126,

) and similar prokaryotic proteins. HcgA is a radical S-adenosyl methionine enzyme involved in the biosynthesis of the iron-guanylylpyridinol (FeGP) cofactor .
DNA-binding protein, curved-DNA (DNA-bd_curved-DNA)
Type: Family

This entry represents DNA-binding proteins that preferentially recognise a curved DNA sequence. It is probably a functional analog of DnaJ; displaying overlapping activities with DnaJ, but functions under different conditions, probably acting as a molecular chaperone in an adaptive response to environmental stresses other than heatshock. these proteins lack autonomous chaperone activity and bind native substrates and targets them for recognition by DnaK. Their activity is inhibited by the binding of CbpM .
[FeFe]-hydrogenase system regulator TM1266 (FeFe-hyd_TM1266)
Type: Family

Members of this protein family occur as part of a system for producing iron-only hydrogenases, dependent on radical SAM proteins HydE and HydG and GTPase HydF. One member of this family, TM_1266 from Thermotoga maritima, has a known crystal structure. The small size, about 80 residues, and a distant relationship to the nickel regulator NikR of the CopG transcriptional regulator family suggest a role as a transcription factor.
Chloride channel, ClcA (Cl-channel_ClcA)
Type: Family

This entry represents a proton-coupled chloride transporter, which functions as an antiport system and exchanges two chloride ions for one proton. It probably acts as an electrical shunt for an outwardly-directed proton pump that is linked to amino acid decarboxylation, as part of the extreme acid resistance (XAR) response .
Conserved hypothetical protein CHP03960, radical SAM (CHP03960_rSAM)
Type: Family

This entry describes a radical SAM protein, or protein region, regularly found paired with or fused to a region described by

. PSI-BLAST analysis of

suggests a relationship to the tRNA pseudouridine synthase TruA, suggesting that this system may act in RNA modification.
Archaeal radical SAM protein, PTO1314 family (rSAM_PTO1314)
Type: Family

Members of this protein family average about 340 residues in length, with a radical SAM domain in the N-terminal 200 residues. The taxonomic distribution is restricted to non-methanogenic archaea, including Picrophilus torridus (locus PTO1314), Sulfolobus sp., Thermoplasma sp., Picrophilus torridus, and Metallosphaera sedula. The gene neighbourhood is not conserved, and the function of this family is unknown.
Aliphatic acid kinase, short-chain, conserved site (Aliphatic_acid_kinase_CS)
Type: Conserved_site

Acetate kinase, which is predominantly found in microorganisms, facilitates the production of acetyl-CoA by phosphorylating acetate in the presence of ATP and a divalent cation . The enzyme is important in the process of glycolysis, enzyme levels being increased in the presence of excess glucose. The growth of a bacterial mutant lacking acetate kinase has been shown to be inhibited by glucose, suggesting that the enzyme is involved in excretion of excess carbohydrate . A related enzyme, butyrate kinase, facilitates the formation of butyryl-CoA by phosphorylating butyrate in the presence of ATP to form butyryl phosphate .

This entry contains two signature patterns for these enzymes; the first one is located in the N-terminal section and the second in the central section. Both of them are glycine-rich and could be involved in substrate or ATP-binding.
2,3-diaminopropionate biosynthesis protein SbnB (SbnB)
Type: Family

Members of this protein family are probable NAD-dependent dehydrogenases related to the alanine dehydrogenase of Archaeoglobus fulgidus (see

) and, more distantly, to ornithine cyclodeaminase. Members include the staphylobactin biosynthesis protein SbnB. Together with SbnA, SbnB is encoded by the staphyloferrin B biosynthetic gene cluster. 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 .
Anaerobic sulphatase maturase, radical SAM (Sulphatase_maturase_rSAM)
Type: Family

Proteins in this entry include ChuR from Bacteroides thetaiotaomicron and AnSME (also known as CPF_0616) from Clostridium perfringens. ChuR is involved in 'Ser-type' sulfatase maturation under anaerobic conditions , while AnSME is involved in 'Cys-type' sulfatase maturation under anaerobic conditions .

Members of this protein family are radical SAM family enzymes, maturases that prepare the oxygen-sensitive radical required in the active site of anaerobic sulphatases. This maturase role has led to many misleading legacy annotations suggesting that this enzyme maturase is instead a sulphatase regulatory protein. All members of the seed alignment are radical SAM enzymes encoded next to or near an anaerobic sulphatase. Note that a single genome may encode more than one sulphatase/maturase pair.
7-carboxy-7-deazaguanine synthase, Clostridial form (7-CO-7-deazaGua_synth_put_Clo)
Type: Family

This entry represents Clostridial form of the 7-carboxy-7-deazaguanine synthases. They are encoded in preQ0 operons found in species that lack members of the related protein family

.

7-deazapurines are compounds that contain pyrrolopyrimidine functional groups (similar to purines, but lacking one of the nitrogens in the pentameric ring). These compounds form a structurally diverse class of nucleoside analogues that often possess antibiotic, antineoplastic, or antiviral activities. Examples of 7-deazapurines that are important for cell function include the bacterial/eukaryotic modified tRNA base queuosine and the archaeal modified base archaeosine. 7-cyano-7-deazaguanosine (preQ0) is the precursor for all 7-deazapurines and is produced from GTP in a four-step pathway . 7-carboxy-7-deazaguanine synthase catalyses the third step in this pathway, the conversion of 6-carboxy-5,6,7,8-tetrahydropterin to 7-carboxy-7-deazaguanine.
tRNA adenosine deaminase-associated protein, putative (tRNA_Adeno_NH3ase_assoc_put)
Type: Family

This entry describes a family of proteins about 200 amino acids in length with only five invariant residues, including an Arg, a Ser-Asp pair, and two Gly residues. Members always are found exclusively in Actinobacteria, and always adjacent to homologues of TadA, a tRNA-specific adenosine deaminase from Escherichia coli. This suggests a housekeeping function in tRNA metabolism.
Poly-beta-1,6 N-acetyl-D-glucosamine export porin PgaA (PGA_export_porin_PgaA)
Type: Family

Members of this protein family are the poly-beta-1,6 N-acetyl-D-glucosamine (PGA) export porin PgaA of Gram-negative bacteria. There is no counterpart in the poly-beta-1,6 N-acetyl-D-glucosamine biosynthesis systems of Gram-positive bacteria such as Staphylococcus epidermidis. The PGA polysaccharide adhesin is a critical determinant of biofilm formation. This enzyme exports PGA across the outer membrane. The PGA transported seems to be partially N-deacetylated since N-deacetylation of PGA by PgaB is needed for PGA export through the PgaA porin .

This outer membrane protein contains a predicted C-terminal β-barrel porin domain and a N-terminal periplasmic superhelical domain containing tetratricopeptide repeats, which may mediate protein-protein interactions, perhaps with PgaB .
Mycofactocin precursor peptide peptidase (MftE)
Type: Family

This entry represents the Mycofactocin precursor peptide peptidase MftE, a peptidase involved in the biosynthesis of the enzyme cofactor mycofactocin (MFT) . It catalyses the cleavage of the MftC-modified MftA peptide to liberate its final two residues, which consist of a cross-linked valine-decarboxylated tyrosine dipeptide (named 3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethyl-2-pyrrolidin-2-one or ADHP) . It is also required for alcohol metabolism in Mycobacteria . This enzyme belongs to the creatinine amidohydrolase family .
Poly-beta-1,6-N-acetyl-D-glucosamine N-deacetylase (PNAG_deacetylase)
Type: Family

A common motif in bacterial biosynthesis of polysaccharide for export is modification that follows polymerisation. This entry describes a family of polysaccharide N-deacetylases that act on poly-beta-1,6-N-acetyl-D-glucosamine as produced by Staphylococcus epidermidis and S. aureus. The end product in these species is designated polysaccharide intercellular adhesin (PIA), which is a biofilm adhesin polysaccharide. The N-deacetylation step is crucial for attachment of the polysaccharide to the bacterial cell surface; it leads to the introduction of positive charges in the otherwise neutral PIA polymer, allowing electrostatic interactions .
[FeFe]-hydrogenase H-cluster maturation GTPase HydF (FeFe-hyd_GTPase_HydF)
Type: Family

This entry describes the family of the [Fe] hydrogenase maturation protein HypF as characterised in Chlamydomonas reinhardtii. It is found in an operon with radical SAM proteins HydE and HydG in numerous bacteria. It has GTPase activity, can bind an 4Fe-4S cluster, and is essential for hydrogenase activity .
DNA modification/repair radical SAM protein, putative (DNA_rSAM_put)
Type: Family

This entry represents a family of uncharacterised protein of about 400 amino acids in length that contains a radical SAM domain in the N-terminal half. Members of this family are present in about twenty percent of prokaryotic genomes, always paired with a member of the conserved hypothetical protein

. Roughly forty percent of the members of that family exist as fusions with a uracil-DNA glycosylase-like region,

. In DNA, uracil results from deamidation of cytosine, forming U/G mismatches that lead to mutation, and so uracil-DNA glycosylase is a DNA repair enzyme. This indirect connection, and the recurring role or radical SAM proteins in modification chemistries, suggest that this protein may act in DNA modification, repair, or both.
DNA repair protein, putative (DNA_repair_put)
Type: Family

This entry represents a family of conserved hypothetical proteins that almost invariably pair with an uncharacterised radical SAM protein. The pair occurs in about twenty percent of completed prokaryotic genomes. About forty percent of the members of this family occur as fusion proteins, where the C-terminal domain belongs to the uracil-DNA glycosylase family, a DNA repair family (because uracil in DNA is deamidated cytosine). The linkage by gene clustering and correlated species distribution to a radical SAM protein, and by gene fusion to a DNA repair protein family, suggests a role in DNA modification and/or repair.
Pyrrolysyl-tRNA ligase, C-terminal (Pyrrolysyl-tRNA_ligase_C)
Type: Domain

PylS is the enzyme responsible for charging the pyrrolysine tRNA, PylT, by ligating a free molecule of pyrrolysine. Pyrrolysine is encoded at an in-frame UAG (amber) at least in several corrinoid-dependent methyltransferases of the archaeal genera Methanosarcina and Methanococcoides, such as trimethylamine methyltransferase. This protein occurs as a fusion protein in Methanosarcina but as split genes in Desulfitobacterium hafniense and other bacteria.
Pyrrolysyl-tRNA ligase, N-terminal (Pyrrolysyl-tRNA_ligase_N)
Type: Domain

PylS is the enzyme responsible for charging the pyrrolysine tRNA, PylT, by ligating a free molecule of pyrrolysine . Pyrrolysine is encoded at an in-frame UAG (amber) at least in several corrinoid-dependent methyltransferases of the archaeal genera Methanosarcina and Methanococcoides, such as trimethylamine methyltransferase. This protein occurs as a fusion protein in Methanosarcina but as split genes in Desulfitobacterium hafniense and other bacteria. This entry describes the small, N-terminal domain.
Quinohemoprotein amine dehydrogenase, beta subunit (QH-AmDH_bsu)
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 beta subunit.
Benzylsuccinate synthase activating enzyme (Benzylsucc_Synthase_activating)
Type: Family

Proteins in this entry are thought to be radical SAM benzylsuccinate synthase-activating enzymes. They are a glycyl radical active site-creating enzyme related to pyruvate formate lyase-activating enzyme and additional uncharacterised homologues which activate additional glycyl radical-containing enzymes .
N-acetyl-alpha-D-glucosaminyl L-malate synthase BshA (Thiol_BshA)
Type: Family

Members of this protein family are BshA, a glycosyltransferase required for bacillithiol biosynthesis. BshA catalyzes the formation of the first intermediate, GlcNAc-Mal, using L-malate and the glucosamine donor substrate UDP-N-acetylglucosamine (UDP-GlcNAc) as substrates. Bacillithiol is a low-molecular-weight thiol, an analogue of glutathione and mycothiol, and is found largely in the Firmicutes .
Colanic acid biosynthesis WcaM (Colanic_acid_synth_WcaM)
Type: Family

This protein of uncharacterised function is the final gene in the conserved colanic acid biosynthesis cluster observed in Enterobacteraceae .
Conserved hypothetical protein CHP03980, redox-disulphide (CHP03980_redox-disulphide)
Type: Family

Members of this protein family all contain an apparent redox-active disulphide. In at least one family member, a cysteine in the CXXC motif is substituted by a selenocysteine. The family is sometimes found adjacent to (and, on occasion, fused with) members of the hybrid-cluster (prismane) family or the nitrite/sulphite reductase family.