SII-SWORD/CoKE huggingface dataset:
Insertion sequence IS21-like ATPase IstB (IstB)
Type: Family

This family represents the AAA+ ATPases of IS21 family IS (insertion sequence) elements, known as IstB, which regulates IS21 transposon function . IstB assembles into a clamshell-shaped decamer that sandwiches DNA between two helical pentamers of ATP-associated AAA+ domains. This complex is recognised by IS21 transposase and promotes its disassembly by stimulating ATP hydrolysis.
SemiSWEET transporter (SemiSWEET)
Type: Family

The SWEET (Sugars Will Eventually be Exported Transporter) is a superfamily of sugar transporters found in both eukaryotes and prokaryotes. Eukaryotic SWEETs usually have seven transmembrane helices (TMHs), but most prokaryotic SWEETs (SemiSWEETs) have only three TMHs. This entry represents prokaryotic SWEETs (SemiSWEETs), which have 3 TMHs .
Transcription antitermination protein LoaP (Transcription_antiterm_LoaP)
Type: Family

This entry represents LoaP, a paralog of NusG with an extensive presence in Bacillota and Actinomycetota. The founding member, LoaP from Bacillus amyloliquefaciens (

), was shown to serve as an antiterminator for the transcription of genes involved in antibiotic biosynthesis .
Sugar transporter SWEET (SWEET)
Type: Family

The SWEET (Sugars Will Eventually be Exported Transporter) is a superfamily of sugar transporters found in both eukaryotes and prokaryotes. Eukaryotic SWEETs usually have seven transmembrane helices (TMHs), but most prokaryotic SWEETs (SemiSWEETs,

) have only three TMHs . This entry represents eukaryotic SWEETs, which are specific sugar efflux transporters essential for the maintenance of animal blood glucose levels, plant nectar production, and plant seed and pollen development . They can carry mono- and disaccharides across a membrane following the concentration gradient. In many organisms it mediates glucose transport ; in Arabidopsis it is necessary for pollen viability; and two of the rice homologues are specifically exploited by bacterial pathogens for virulence by means of direct binding of a bacterial effector to the SWEET promoter .
Competence protein ComGG, Streptococcus-type (ComGG_streptococcus-type)
Type: Family

ComGG is an especially variable protein of ComG-like DNA binding/uptake type IV pilus formation systems. This entry represents ComGG proteins found mainly in Streptococcus and Enterococcus species but not Bacillus.

The comG operon of Bacillus subtilis encodes seven membrane associated proteins which function in binding of transforming DNA to the competent cell surface . ComGC, GD, GE and GG have N-terminal sequence motifs typical of type 4 pre-pilins and are processed by a pathway that requires the product of comC, also an essential competence gene. They form pilin-like structures that are localised to the cytoplasmic membrane and cell wall . The comG operon also consist of ComGF, a small integral membrane protein, ComGA and ComGB, which are predicted to be a nucleotide binding protein and an integral membrane protein respectively . When strains missing each of the 7 proteins are created, they were all found to be nontransformable and failed to bind transforming DNA to the cell surface .
ANR transcriptional regulator (ANR_neg_reg)
Type: Family

This entry represents a group of proteins from tailed bacteriophages and prophages from proteobacteria known as the ANR family of transcriptional regulators, which includes the AggR-activated regulator Aar found in pathogenic Enterobacteriaceae and Pasteurellaceae. The name ANR (AraC Negative Regulators) refers to an effect on, rather than homology to, certain AraC family transcriptional regulators . Aar is likely to act directly or indirectly as a virulence suppressor and perhaps modulate virulence as a result of selection towards clinical attenuation. This hypothesis is supported by increased pathogenicity in aar-negative strains in Mali and Brazil .
Competence type IV pilus ATPase ComGA (ATPase_ComGA)
Type: Family

This entry represents a group of proteins from bacillales and lactobacillales, including ComG operon protein 1 from Bacillus subtilis (ComGA), which is required for uptake of DNA by competent cells . All members of this protein family contain the domain

.
DsrMKJOP redox complex, subunit DsrJ (DsrJ)
Type: Family

This family represents homologs of the DsrJ subunit of the DsrMKJOP complex from Desulfovibrio desulfuricans (

). This membrane-bound redox complex is involved in sulfate reduction in sulfate-reducing organisms (SROs) . The dsrJ gene encodes a triheme periplasmic cytochrome c subunit, which contains three conserved heme c-binding sites (CXXCH) at the C terminus.

A member of this family is also HmeE from Archaeoglobus fulgidus, the mature form of which contains an N-terminal hydrophobic stretch predicted to form a transmembrane α-helix that may anchor the protein into the membrane .
MtrAB system histidine kinase MtrB (MtrAB_MtrB)
Type: Family

This family represents the sensor histidine kinase MtrB, which is a member of the two-component regulatory system MtrA/MtrB. It functions as a membrane-associated protein kinase that phosphorylates MtrA in response to environmental signals. MtrB may be active only at septa where it promotes MtrA phosphorylation and MtrA regulon expression, probably playing a role in cell division .
YfjT-like (YfjT-like)
Type: Family

This is a family of small (~60 residues long) uncharacterised bacterial proteins . They are predicted to fold into α-helical hairpin.
MtrAB system response regulator MtrA (MtrAB_MtrA)
Type: Family

This entry includes the DNA-binding response regulator MtrA, which is a member of MtrA/MtrB, a highly conserved two-component system (TCS) implicated in the regulation of cell division in the actinobacteria, playing a role in secondary metabolism and morphological development . In unicellular Mycobacterium tuberculosis, MtrAB coordinates DNA replication with cell division and regulates the transcription of resuscitation-promoting factor B where MtrA is essential . In filamentous Streptomyces venezuelae, it links antibiotic production to sporulation .

MtrA binds to a consensus recognition sequence, composed of a 17-nt sequence containing two direct repeats of six nt, and needs to be phosphorylated to act in regulon expression. In Streptomyces, MtrA has been additionally described as a novel nitrogen metabolism regulator . MtrA belongs to the OmpR family of DNA-binding response regulators that contain N-terminal receiver (REC) domain and C-terminal DNA-binding winged helix-turn-helix effector domains.
Cyclopropane mycolic acid synthase, actinobacteria (CMAS_actinobact)
Type: Family

This entry represents cyclopropane mycolic acid synthases (CMAS) and similar sequences from actinobacteria, including tailoring enzymes that make site-specific modifications to mycolic acid precursor molecules. These include Mycobacterium tuberculosis enzymes MmaA1-MmaA4, CmaA1-CmaA2, and PcaA. The family also includes S-adenosylmethionine-dependent methyltransferase UmaA, reported to be the lone member of this family not involved in mycolic acid biosynthesis. No members of this family are found in species that lack mycolic acids. This protein family excludes two more distantly related paralogs, UfaA1 and Rv3720, that are also encoded in the Mycobacterium tuberculosis H37Rv genome .
MtrA, receiver domain (MtrA_REC)
Type: Domain

This is the phosphoacceptor receiver (REC) domain of MtrA. REC domains function as phosphorylation-mediated switches within response regulators, but some also transfer phosphoryl groups in multistep phosphorelays. This domain adopts a classical α/β fold with Flavodoxin-like topology and its phosphorylation modulates the protein activity .

This entry includes the DNA-binding response regulator MtrA, which is a member of MtrA/MtrB, a highly conserved two-component system (TCS) implicated in the regulation of cell division in the actinobacteria, playing a role in secondary metabolism and morphological development . In unicellular Mycobacterium tuberculosis, MtrAB coordinates DNA replication with cell division and regulates the transcription of resuscitation-promoting factor B where MtrA is essential . In filamentous Streptomyces venezuelae, it links antibiotic production to sporulation .

MtrA binds to a consensus recognition sequence, composed of a 17-nt sequence containing two direct repeats of six nt, and needs to be phosphorylated to act in regulon expression. In Streptomyces, MtrA has been additionally described as a novel nitrogen metabolism regulator . MtrA belongs to the OmpR family of DNA-binding response regulators that contain N-terminal receiver (REC) domain and C-terminal DNA-binding winged helix-turn-helix effector domains.
CAL67264-like (CAL67264-like)
Type: Family

This family includes CAL65096 (

,

) from Gramella forsetii and similar sequences mainly found in flavobacteriales. Members of this family are small, well-conserved, hydrophobic, lineage-restricted proteins, about 60 amino acids in length, with an essentially invariant C-terminal motif LKGRV. They are predicted to fold into an α-helical hairpin.
Putative zinc-binding domain (Putative_zinc-bd)
Type: Domain

This entry represents a small (~40 residues in length) domain that is found in a group of uncharacterised proteins. This domain contains three conserved cysteines and a histidine that could potentially bind to zinc. This putative zinc-finger is very likely to adopt structure similar to GATA-like zinc-fingers.
FxLYD domain (FxLYD_dom)
Type: Domain

This entry represents the uncharacterised FxLYD domain, named for the strongest (but not invariant) motif, which spans about 75 amino acids usually in the C-terminal region of the these group of proteins. This domain is found mainly in bacteria but also in some archaeal species. In some proteins, this domain is found in two tandem copies.
GDCCVxC domain (GDCCVxC)
Type: Domain

This entry represents a domain found in a group of uncharacterised prokaryotic selenoproteins . It contains a conserved sequence GDCCVxC. The function of this domain is unknown.
Dehydratase YjiM-like (YjiM-like)
Type: Family

This entry represents a group of double-cubane proteins specific to anaerobes (facultative or obligate), including Putative dehydratase subunit YjiM from Escherichia coli and Putative dehydratase subunit MJ0007 from Methanocaldococcus jannaschii. These enzymes always co-occur with an accessory protein, an ATP-dependent activase. The cofactor contains a pair of 4Fe-4S cubane clusters, bridged by a sulfur atom, for an overall 8Fe-9S cofactor structure. Bacterial members of this protein family coexist with SelD, the selenium donor protein required for biosynthesis of selenoproteins, selenouridine-modified tRNAs, selenium-dependent molybdenum hydroxylases, and selenoneine .
Probable ATP-binding protein BrxC (BREX_BrxC)
Type: Family

This entry represents the BREX system Probable ATP-binding protein BrxC, mainly found in bacteria.

BrxC is a P-loop-containing, probable ATPase associated with type 1 BREX (bacteriophage exclusion) systems, which provide immunity against bacteriophage infections by methylating specific DNA sites to distinguish self from non-self . Although phage adsorption is permitted, BREX systems block phage DNA replication. BrxC, a probable ATP-binding protein, operates within a six-protein complex (BrxA-BrxB-BrxC-PglX-PglZ-BrxL) that confers resistance to a range of bacteriophages.
Serine protease MarP-like (MarP-like)
Type: Family

The founding member of this family of membrane-spanning serine proteases, which is found mainly in Actinobacteria, is the acid resistance periplasmic serine protease MarP of Mycobacterium tuberculosis. Recent work shows that MarP is required to cleave and activate the peptidoglycan hydrolase RipA, and loss of RipA activity creates a defect in progeny separation during cell division. Therefore, the requirement for MarP in order to survive acidic conditions may be a consequence of peptidoglycan hydrolysis requirements, explaining why MarP family members are distributed more broadly in the Actinobacteria than the subset of species capable of surviving intracellularly as pathogens .
PPA1309-like (PPA1309-like)
Type: Family

This entry represents a family of uncharacterised proteins restricted to the Actinobacteria but absent from the genus Mycobacterium, including PPA1309 from Cutibacterium (Propionibacterium) acnes (

).
Septation protein SepH-like (SepH-like)
Type: Family

Septation protein H (SepH) was firstly characterised in Streptomyces venezuelae, and homologs were identified in Mycobacterium smegmatis (recently renamed to Mycolicibacterium smegmatis). SepH contains a N-terminal DUF3071 domain (

) and a conserved C-terminal region. It binds directly to cell division protein FtsZ to stimulate the assembly of FtsZ protofilaments .
Benzoate 1,2-dioxygenase reductase, FAD/NAD binding domain (BenC-like_FAD_NAD-bd)
Type: Domain

This entry represents the FAD/NAD binding domain of Benzoate 1,2-dioxygenase electron transfer component (BenC) and similar sequences from prokaryotes and actinobacteria. In this dioxygenase, the FAD/NAD(P) binding domain (the reductase) is involved in transfer of electrons from NAD(P)H to the oxygenase component which insert into an aromatic substrate, that constitutes the initial step in microbial aerobic degradation of aromatic rings. This signature spans two structural domains, the FAD-binding β-barrel domain and the NAD-binding domain that has an α/β structure consisting of a five-stranded β-sheet with two helices positioned on each side of the sheet .

Oxygenases oxidise hydrocarbons using dioxygen as the oxidant. As a Class I bacterial dioxygenases, benzoate dioxygenase like proteins combine an [2Fe-2S] cluster containing N-terminal ferredoxin at the end fused to an FAD/NADP(P) domain. Flavin oxidoreductases use flavins as substrates, unlike flavoenzymes which have a flavin prosthetic group .
Iron uptake porin Som-like (Por_som-like)
Type: Family

Proteins of this family have typical porin structures. It has been reported that Synechococcus outer membrane (Som) porins (SomA and SomB) are involved in iron uptake in cyanobacterium Synechococcus .
Copper resistance protein CopC-like (CopC-like)
Type: Family

This family includes Copper resistance protein C (CopC), which mediates copper resistance by sequestration of copper in the periplasm along with the copper-binding protein CopA . This entry also includes protein YobA from E. coli, which is uncharacterised.
Benzoate diol dehydrogenase BenD (BenD)
Type: Family

This entry represents Benzoate diol dehydrogenase BenD, also known as 1,6-dihydroxycyclohexa-2,4-diene-1-carboxylate dehydrogenase (

), and similar proteins from proteobacteria and actinobacteria. BenD catalyses the degradation of 2-hydro-1,2-dihydroxy benzoate (DHB) to catechol .
4-oxalomesaconate tautomerase-like (OMA_tautomer-like)
Type: Family

This family represents a group of bacterial isomerases, including OMA isomerases (also known as 4-oxalomesaconate tautomerase GalD in Pseudomonas putida and LigU from Sphingomonas sp. (strain KA1)). GalD catalyses the tautomerization of the 4-oxalomesaconic acid keto (OMAketo) generated by GalA dioxygenase to 4-oxalomesaconic acid enol (OMAenol) and mediates the second step in gallate degradation pathway. LigU contributes to the degradation of lignin at the level of the protocatechuate 4,5-cleavage pathway. It catalyses the isomerization of the double bond between C4 and C5 in (4E)-oxalomesaconate (OMA) to (3Z)-2-keto-4-carboxy-3-hexenedioate (KCH), where the double bond has migrated between C3 and C4 via a 1,3-allylic isomerization . The uncharacterised isomerase YbhH from E. coli is also a member of this entry.
DNA endonuclease SmrA (Endonuc_SmrA)
Type: Family

This entry represents DNA endonuclease SmrA from Escherichia coli and similar sequences from gammaproteobacteria. SmrA, also known as YdaL, is a small endonuclease with homology to the C-terminal domain found in the endonuclease MutS2, but not found in the related mismatch repair protein MutS. The biological role of this endonuclease is not yet known .
Copper resistance protein D (CopD)
Type: Family

CopD is an inner membrane protein encoded in Gram-negative bacterial systems that provide resistance to excess copper. It is typically chromosomal, although the PcoD protein of the plasmid-borne pco copper resistance system is a exceptional member of the CopD family. CopD, together with CopC, perform copper uptake into the cytoplasm .
Uncharacterised protein family IPExxxVDY (IPExxxVDY_fam)
Type: Family

This entry represents a family of uncharacterised proteins from bacteroidetes. Member proteins average about 160 amino acids in size, and feature two widely separated invariant Asn residues, as well as the larger (though less invariant) motif for which the family is named.
GT4 family glycosyltransferase PelF-like (PelF-like)
Type: Family

Proteins of this family are components of the exopolysaccharide Pel transporter. It has been reported that PelF is a soluble glycosyltransferase that uses UDP-glucose as the substrate for the synthesis of exopolysaccharide Pel, whereas PelG is a Wzx-like and PST family exopolysaccharide transporter .
Competence type IV pilus assembly protein ComGB (T4P_ComGB)
Type: Family

This entry represents a group of proteins specific to Bacillales and Lactobacillales that form part of a type IV pilus system used for DNA binding and uptake during natural transformation . Members of this family are typically called ComGB (second protein of the ComG operon), which belong more broadly to the family of GspF, part of type 2 secretion systems (T2SS) in Gram-negative bacteria.
RNA-guided endonuclease IscB-like (RNA-guided_IscB-like)
Type: Family

This entry represents a group of prokaryotic proteins with an RRXRR domain (

), including the putative nuclease IscB . Many members also contain a HNH nuclease domain (

).
Lipid A hydroxylase LpxO-like (Lipid_A_LpxO-like)
Type: Family

This entry represents Lipid A hydroxylase LpxO and similar sequences from proteobacteria. LpxO is an enzyme that modifies one of the lipid chains in lipid A by hydroxylation, with resulting changes in resistance to the host immune response and to the antibiotic colistin. This family includes LpxO1 from Pseudomonas aeruginosa, but not its paralog LpxO2 .
Type IV secretion system, VirB10/PtlG (T4SS_VirB10/PtlG)
Type: Family

This entry represents a group of proteins mainly from proteobacteria, including VirB10 from Brucella abortus and PtlG from Bordetella pertussis. Virb10 seems to be per se essential for intracellular multiplication within non-professional phagocytes and is essential for pathogenesis in mice . PtlG is involved in the secretion of assembled pertussis toxin (PTX) through the outer membrane .
Cell division inhibitor SulA, enterobacterial type (SulA_enterobact)
Type: Family

This entry represents a group of proteins specific to enterobacterales, including Cell division inhibitor SulA from Escherichia coli, a cell division inhibitor induced by the SOS response. This protein interacts with FtsZ to halt cell division . SulA proteins, like FtsZ, differ greatly by lineage, with SulA from Pseudomonas showing a different architecture.
Zinc metallochaperone AztD-like (AztD-like)
Type: Family

This entry represents AztD from Paracoccus denitrificans (

) and similar sequences mainly found in actinomycetes and alphaproteobacteria. AztD, a component of the AztABCD zinc-uptake system, is a zinc chaperone to AztC (

), and it may store zinc in the periplasm for transfer through the AztABCD transporter system .
Nitroreductase subunit ArsF-like (ArsF-like)
Type: Family

This entry represents ArsF from Shewanella putrefaciens (

) and similar prokaryotic sequences. ArsF acts together with ArsE as a nitroreductase for trivalent forms (having As(III) instead of As(V)) of two synthetic aromatic organoarsenical biocides, nitarsone and roxarsone, reducing the nitro group to an amine, after which efflux confers resistance to the arsenical . Because the nitro group is rather far from the As(III) moiety of the known substrates, it is likely that conversed properties of members of this family include nitroreductase activity but not arsenical resistance activity.

Members of this family are likely to adopt Thioredoxin-like fold.
Transporter permease, putative, prefix domain (Permease_put_prefix)
Type: Domain

This entry represents a domain found at the N-terminal end of a group of bacterial putative permeases resembling ABC transporter permeases. In some permease families, this domain may be replaced by a different, seemingly unrelated domain.

This domain is predicted to fold into an α-helical hairpin.
Nitrate/nitrite transporter NrtS-like (NrtS-like)
Type: Family

This entry represents NrtS from Synechococcus sp. PCC 7002 and similar bacterial sequences. It includes both NrtS1 and NrtS2 proteins, which share significant sequence similarity and conserved motifs. These proteins are encoded by two neighboring genes on Synechococcus sp. PCC 7002 genome. NrtS1 and NrtS2 form a heteromeric transporter complex that was shown to transport nitrite as well as nitrate .
Zinc ABC transporter, substrate-binding protein AztC-like (AztC-like)
Type: Family

This family represents AztC from Paracoccus denitrificans (

) and similar proteins from actinomycetes and alphaproteobacteria. AztC is a component of the AztABCD zinc-uptake system. Like most ABC transporter genes, AztC is encoded in an operon with the canonical ATPase (AztA) and permease (AztB) genes . However, the azt operon is unusual in that it includes a fourth gene, AztD (

), a metallochaperone that transfers zinc directly to AztC through a specific, associative mechanism .

AztC can acquire zinc either from solution or from the metallochaperone AztD. AztC is composed of two structurally related α/β domains connected by a long α-helix. The zinc-binding site is located in the cleft between domains. Crystal structures for holo- and apoAztC suggest significant structural changes accompanying zinc binding .
VgrG-related (VgrG-rel)
Type: Family

This family represents proteins from actinobacteria that resemble VgrG proteins of type VI secretion systems (T6SS) occurring in proteobacteria. The biological roles and molecular functions of these proteins are unknown.
SCO2322-like domain (SCO2322-like)
Type: Domain

This entry represents a domain is found in a number of uncharacterised proteins from actinomycetes. It is predicted to have a circularly permuted ubiquitin-like fold. In some instances, this domain is followed by the GPS-CTERM domain (

).
GPS-CTERM domain (GPS-CTERM)
Type: Domain

This entry represents the GPS-CTERM domain found at the C-terminal of proteins from actinomycetes, such as Nocardia and Streptomyces. It usually follows the SCO2322-like domain (

). This is an apparent novel protein-sorting domain.
AimR transcriptional regulator-like (AimR-like)
Type: Family

This entry represents a group of proteins found in tailed bacteriophages and prophages mainly found in firmicutes, including AimR transcriptional regulator from Bacillus phage. AimR (arbitrium receptor), which is a part of the so-called phage arbitrium system, is a DNA-binding phage regulatory protein that acts as a receptor for a 6-amino acid signalling peptide cleaved from the C terminus of AimP. AimR controls expression of AimX, the third member of the quorum sensing-like arbitrium system and an inhibitor of phage lysogeny . The arbitrium system enables a descendant phage to 'communicate' with its predecessors, that is, to estimate the amount of recent previous infections and hence decide whether to employ the lytic or lysogenic cycle.

AimR assembles an α-α superhelix fold and accommodates the signalling peptide encircled by its tetratricopeptide repeats, which is reminiscent of RRNPP family members from the quorum-sensing system . With or without the peptide, AimR dimerises through the C-terminal capping helix. It contains HTH motif at the N terminus that is crucial for DNA targeting.

This group of proteins also includes YopK from Bacillus subtilis .