SII-SWORD/CoKE huggingface dataset:
Choline TMA-lyase-activating enzyme (CutC_activ_rSAM)
Type: Family

A gene cluster responsible for anaerobic choline degradation has been identified within the genome of sulfate-reducing bacteria. The choline utilisation (cut) gene cluster consist of cutC and cutD. Members of this family are CutD, a radical enzyme that serves as an activase for choline TMA-lyase, CutC. CutC is a glycyl radical enzyme related to pyruvate formate-lyase. CutD is related to pyruvate formate-lyase activase .
Surface carbohydrate biosynthesis protein (Surf_polysacc)
Type: Family

This entry includes uncharacterised proteins related to surface carbohydrate biosynthesis. This family shows distant homology to regions of family

, of spore coat polysaccharide biosynthesis protein SpsB from Bacillus subtilis, etc.
Encapsulin-associated ferritin-like (Ferrit_encaps)
Type: Family

Two families of proteins are encoded next to the encapsulin gene (

): one is an enzyme family that includes Dyp-type peroxidases, the other resembles the bacterioferritins and is represented by this entry. Encapsulin-associated forms of the proteins in these two families have a necessary C-terminal motif that resembles DGSL[SGN]IGSL[KR].

Members of these entry are cargo proteins of the encapsulin nanocompartment . These are ferritin-like ferroxidases that mineralizes iron inside the encapsulin nanocompartment . Converts Fe2 to Fe3 that is released to the exterior of the decameric complex for deposition in the encapsulin nanocompartment. In solution the decamer binds 10-15 iron cations; in the encapsulin nanocompartment the decamer can bind up to 48 ions, perhaps via its internal channel and on its exterior. The empty encapsulin nanocompartment sequesters about 2200 Fe ions while the cargo-loaded nanocompartment can maximally sequester about 4150 Fe ions. EncFtn retains ferroxidase activity when encapsulated .
Protein translocase subunit SecA 2, Bacillus anthracis-type (SecA2_Bac_anthr)
Type: Family

In bacteria, the majority of exported proteins are transported by the general Sec pathway from their site of synthesis in the cytoplasm across the cytoplasmic membrane. The ATPase SecA powers this Sec-mediated export . Members of this family always occur in genomes with the preprotein translocase SecA (

) and closely resemble it, hence the designation SecA2. However, this appears to be a different type of accessory Sec system SecA2 from the serine-rich glycoprotein type found in Staphylococcus and Streptococcus (

), and the actinobacterial SecA2 (

). This type occurs in species such as Bacillus anthracis, Geobacillus thermoglucosidasius, Solibacillus silvestris, etc .
IMEF encapsulin system ferritin-like cargo (IMEF_cargo)
Type: Family

Proteins in this entry are part of the iron-mineralizing encapsulin-associated Firmicute (IMEF) system found in encapsulin nanocompartments . Encapsulins are involved in microbial iron storage and redox metabolism . The IMEF cargo protein (

) from Quasibacillus thermotolerans (also known as ferritin-like protein) has been characterised as a ferritin-like iron-binding protein that may play a role in iron mineralization in the encapsulin nanocompartment. It has ferroxidase activity even when encapsulated, the rate is probably controlled by the rate of Fe flux across the nanocompartment pores .
SLAP domain (SLAP_dom)
Type: Domain

This domain is duplicated in SlaP (S-layer assembly protein), a partner of SecA2 in the Bacillus anthracis type of accessory Sec system (

). The domain is found, either once or twice, in additional Firmicutes species.
Accessory Sec system S-layer assembly protein (Sec_acc_SLAP)
Type: Family

Members of this family, designated S-layer assembly protein (SlaP), occur next to a Bacillus anthracis-type accessory Sec system SecA2. Members have two tandem copies of a duplicated SLAP domain (

) that may also occur in other contexts. SlaP is found both free in the cytoplasm and membrane-associated. SecA2 and SlaP appear to work together to modify Sec for efficient S-layer secretion .
Arg-Lys translocation region protein phosphatase RktP (RK_trnsloc_Pase)
Type: Family

The Sec-independent protein export system TAT, or twin-arginine translocation, is composed of TatA, TatB, and TatC. The TAT system is unusual in Leptospira, with Lys replacing Arg in the second position of the twin-Arg motif. This protein, restricted to Leptospira and showing distant homology to the phosphoserine phosphatases RsbU and SpoIIE, is always encoded immediately downstream of the tatC gene and appears to be part of the variant TAT system. It lacks a TAT signal itself, and so is more likely to be part of the Sec-independent translocation machinery than to be a substrate . The suggested symbol is rktP, for RK-Translocation Phosphatase.
Copper storage protein 1 family (Csp1_Cys_rich)
Type: Family

This entry represents the copper storage protein (Csp1) and related proteins. Members of this family average about 150 amino acids in length, beginning with a twin-arginine translocation signal sequence, then a His-rich spacer region, followed by a ~105-residue region in which thirteen positions are nearly invariant Cys residues.

Csp1 is a tetramer of four-helix bundles with each monomer binding up to 13 Cu(I) ions via the Cys residues that point into the core of the bundle . The fact that the tetrameric Csp1 is capable of binding up to 52 Cu(I) ions is consistent with a role in copper storage. Experimental data suggests that Csp1 is exported from the cytosol, and stores copper for particulate methane monooxygenase (pMMO).
Mobilome CxxCx(11)CxxC protein (Mob_CxxC_CxxC)
Type: Family

Members of this family share twin CxxC motifs near the C terminus, suggesting a DNA- or RNA-binding activity. The spacing between CxxC motifs is variable, from 11 to 16 amino acids. Members in general occur on plasmids or near other markers of lateral gene transfer (transposases, integrases, endonucleases, etc).
Sporulation killing factor system, radical SAM maturase SkfB (rSAM_SkfB)
Type: Family

Spore formation by the bacterium Bacillus subtilis is a stress response triggered by nutrient limitation. Two operons are strongly induced at the start of sporulation; one of them is skf (for sporulation killing factor). skf produces a killing factor which, together with a signaling protein, act cooperatively to block sister cells from sporulating and cause them to lyse, providing a source of nutrients to support the sporulation process .

The first gene of the skf operon, skfA, encodes a small peptide. SkfA induces the lysis of sibling cells that have not entered the sporulation pathway . The product of the second gene, skfB, encodes a radical SAM enzyme. SkfB creates a sactipeptide (sulfur-to-α-carbon) crosslink of Cys-4 to Met-12 of the mature form of SkfA. In Paenibacillus larvae subsp larvae B-3650, the Met is replaced by Leu, so the modification must be different. SkfB has 2 4Fe-4S clusters, one in its radical SAM domain (

) and one in a region that somewhat resembles the SPASM domain (

) .
ELWxxDGT repeat (ELWxxDGT_rpt)
Type: Repeat

This entry represents a protein repeat with a well-conserved motif ELWxxDGT, and a periodicity of about 48. A single protein may have as many as 18 repeats. It may consist nearly entirely of this repeat, or may have other repeats as well (e.g. hyalin repeat). It is most common in the Deltaproteobacteria.
Cyanoexosortase B-associated protein (Cyanoexo_CrtB_assoc)
Type: Family

Members of this protein family are found exclusively in the Cyanobacteria, usually encoded next to a gene encoding cyanoexosortase B (

). This relationship resembles the association of the unrelated protein family

with cyanoexosortase A (

), and of most exosortases with EpsI.
Polyketide product template domain (PT_fungal_PKS)
Type: Domain

This entry represents the product template (PT) domain of type I polyketide synthases (PKS) and non-reducing PKs from fungi. This domain resembles the dehydratase domain represented by (

). There is a conserved dehydratase active site (His in the first hot dog domain, Asp in the second hot dog domain) found in proteins in both entries .
Sporulation killing factor SkfA (RiPP_SkfA)
Type: Family

Spore formation by the bacterium Bacillus subtilis is a stress response triggered by nutrient limitation. Two operons are strongly induced at the start of sporulation; one of them is skf (for sporulation killing factor). skf produces a killing factor which, together with a signaling protein, act cooperatively to block sister cells from sporulating and cause them to lyse, providing a source of nutrients to support the sporulation process .

The first gene of the skf operon, skfA, encodes a small peptide that is post-translationally modified by a sulfur-to-α-carbon cross-link introduced by a radical SAM enzyme, SkfB (

) . SkfA induces the lysis of sibling cells that have not entered the sporulation pathway .
Sporulation killing factor system integral membrane protein SkfF (SkfF)
Type: Family

Spore formation by the bacterium Bacillus subtilis is a stress response triggered by nutrient limitation. Two operons are strongly induced at the start of sporulation; one of them is skf (for sporulation killing factor). skf produces a killing factor which, together with a signaling protein, act cooperatively to block sister cells from sporulating and cause them to lyse, providing a source of nutrients to support the sporulation process .

The skf operon consists of skfA-H. SkfA induces the lysis of sibling cells that have not entered the sporulation pathway . SkfF has multiple membrane-spanning domains and is encoded next to SkfE, a protein with ATP-binding cassette (ABC) homology, suggesting ABC transporter permease activity for this protein.
LPS export ABC transporter, ATP-binding protein LptB (LPS_export_LptB)
Type: Family

Lipopolysaccharide (LPS) transport across the periplasmic space and its assembly at the Escherichia coli cell surface is carried out by a complex of seven Lpt proteins spanning the inner membrane (LptBCFG), the periplasm (LptA), and the outer membrane (LptDE). Members of this family are LptB, the ATP-binding cassette protein of the ABC transporter complex LptBFG involved in lipopolysaccharide export .
LPS export ABC transporter permease LptF (LptF)
Type: Family

Lipopolysaccharide (LPS) transport across the periplasmic space and its assembly at the Escherichia coli cell surface is carried out by a complex of seven Lpt proteins spanning the inner membrane (LptBCFG), the periplasm (LptA), and the outer membrane (LptDE) . Members of this family are LptF, one of homologous, two tandem-encoded permease genes of an export ATP transporter for lipopolysaccharide (LPS) assembly in most Gram-negative bacteria. The other permease subunit is LptG (

) .
LPS export ABC transporter permease LptG (LptG)
Type: Family

Lipopolysaccharide (LPS) transport across the periplasmic space and its assembly at the Escherichia coli cell surface is carried out by a complex of seven Lpt proteins spanning the inner membrane (LptBCFG), the periplasm (LptA), and the outer membrane (LptDE) . Members of this family are LptG, one of homologous, two tandem-encoded permease genes of an export ATP transporter for lipopolysaccharide (LPS) assembly in most Gram-negative bacteria. The other permease subunit is LptF (

) .
Type II secretion system-associated lipoprotein (Spiro_T2SS_lipo)
Type: Family

Members of this family occur only in spirochetes (Leptospira, Leptonema, Turneriella), as part of a type II secretion system (T2SS) cassette. This small protein (about 100 amino acids) has an N-terminal signal sequence ending with a Cys residue, suggesting it is a lipoprotein.
Type II secretion system protein GspN, Leptospira-type (T2SS_GspN_Lepto)
Type: Family

Members of this family are the N (or GspN) protein of type II secretion systems (T2SS) as found in Leptospira, Geobacter, Myxococcus, and several other genera. Sequence similarity to GspN in

is extremely remote.

The type II secretion system (T2SS) is one of several extracellular secretion systems in gram-negative bacteria. It delivers toxins and a range of hydrolytic enzymes including proteases, lipases and carbohydrate-active enzymes to the cell surface or extracellular space . T2SS systems are composed of 11 to 15 different proteins, which are generally called GspA to GspO and GspS. The T2SS spans the two bacterial membranes and ensures secretion of folded proteins across the outer membrane pore formed by GspD. The inner membrane complex contains GspC, GspL, GspM, and GspF. The cytoplasmic domains of GspL and GspF interact with an ATPase, GspE. GspE is thought to energize the formation of a short pseudopilus by several pilin-like proteins, GspG to GspK . GspD has been shown to interact with the inner membrane component GspC .
Type II secretion system protein GspM, XcpZ-type (T2SS_GspM_XcpZ)
Type: Family

Members of this family are a variant form of the type II secretion system (T2SS) protein M, GspM, as found in several species of Pseudomonas. Members, including XcpZ, are short relatives to proteins in

, but are not recognised by that entry.

The type II secretion system (T2SS) is one of several extracellular secretion systems in gram-negative bacteria. It delivers toxins and a range of hydrolytic enzymes including proteases, lipases and carbohydrate-active enzymes to the cell surface or extracellular space . T2SS systems are composed of 11 to 15 different proteins, which are generally called GspA to GspO and GspS. The T2SS spans the two bacterial membranes and ensures secretion of folded proteins across the outer membrane pore formed by GspD. The inner membrane complex contains GspC, GspL, GspM, and GspF. The cytoplasmic domains of GspL and GspF interact with an ATPase, GspE. GspE is thought to energize the formation of a short pseudopilus by several pilin-like proteins, GspG to GspK . GspD has been shown to interact with the inner membrane component GspC .
CRISPR type MYXAN-associated protein Cmx8 (MYXAN_cmx8)
Type: Family

Members of this family occur only in CRISPR/cas loci of the MYXAN type, but are present in a minority of such systems. This protein shows similar length and composition but only about 12 percent sequence identity to

/

.
Glycosyltransferase Aah/TibC-like (Aah/TibC-like)
Type: Family

Both Aah (autotransporter adhesin heptosyltransferase) and TibC are protein O-heptosyltransferases that act on multiple sites from repeat regions of proteins exported by autotransporters. Aah glycosylates AIDA (autotransporter adhesin involved in diffuse adherence) and TibC acts on TibA (enterotoxigenic invasion locus B). TibC is able to replace Aah, suggesting that both represent a novel class of heptosyltransferases specifically transferring heptose residues onto multiple sites of a protein backbone .
Adhesin of bacterial autotransporter system (AIDA)
Type: Repeat

Adhesin involved in diffuse adherence (AIDA-I) belongs to the group of monomeric autotransporters (AT) and is an important virulence factor that mediates auto-aggregation, biofilm formation, adhesion and invasion into host cells . The AIDA repeat is found on bacterial autotransporter proteins. As the repeat is short and occurs multiple times, it is likely to be the region of the transporter that acts as the stalk between the β-barrel inserted into the membrane and the N-terminal head domain. These repeats contain a 13-residue strand-loop-strand motif which has been been identified as glycosylation sites .
Group II intron reverse transcriptase/maturase (Group_II_RT_mat)
Type: Family

Members of this protein family are multifunctional proteins encoded in most examples of bacterial group II introns. These group II introns are mobile selfish genetic elements, often with multiple highly identical copies per genome. Member proteins have an N-terminal reverse transcriptase (RNA-directed DNA polymerase) domain (

) followed by an RNA-binding maturase domain (

). Some members of this family may have an additional C-terminal DNA endonuclease domain.
Polysaccharide biosynthesis PFTS motif protein (PFTS_polysacc)
Type: Family

Members of this protein family are found in O-antigen biosynthesis loci in Leptospira, two tandem homologues in a polysaccharide biosynthesis region in the archaeon Methanoregula formicicum, in Rhizobium leguminosarum bv. trifolii WSM2297, etc. Members are more strongly conserved in the C-terminal region, where an invariant sequence PFTS is found.
HemN-related non-iron pseudo-SAM protein PsgB (Non_iron_rSAM)
Type: Family

Members of this protein family are related to radical SAM enzymes HemN (oxygen-independent coproporphyrinogen III oxidase) and HutW (a putative heme utilisation enzyme) but lack the signature CxxxCxxC motif for 4Fe-4S binding. Members occur exclusively in Borrelia, which appears to live without iron, as the only radical SAM enzyme homologue in any Borrelia genome. This enzyme has been designated PsgB (Pseudo-SAM, Genus Borrelia) .
Intein C-terminal splicing region (Intein_C)
Type: Conserved_site

Inteins (for INternal proTEINs) are protein insertion sequences that are embedded in host protein sequences. They are post-translationally excised from the host protein by a self-catalytic protein splicing process, in which the intein sequence is precisely excised, and the flanking host protein sequences (N- and C-exteins) are religated to create a functional protein. Intein and protein splicing may be viewed as the protein equivalent of intron and RNA splicing, respectively. Inteins were initially discovered as translated intervening sequences that were present in the host gene but absent in homologous genes. Inteins occur in organisms spanning all three kingdoms of life (eubacteria, archaea and eukaryote). Although many inteins are in host proteins involved in nucleic acid metabolism, several inteins are located in metabolic enzymes, such as phosphoenolpyruvate synthase, anaerobic ribonucleoside triphosphate reductase, UDP-glucose dehydrogenase, ClpP protease/chaperone, vacuolar ATPase proton pump (VMA) and glutamine-fructose 6-phosphate transaminase. It should be noted that protein splicing can also occur in trans as in Synechocystis sp. PCC 6803, where the replicative DNA polymerase catalytic subunit (DnaE) is generated from two separate precursor fragments .

Most inteins are bifunctional proteins mediating both protein splicing and DNA cleavage. The domain involved in splicing is formed by the two terminal splicing regions, which are separated by a small linker in mini-inteins or a homing endonuclease of 200-250 amino acids in larger inteins . The N-terminal splicing region spans the about 100 N-terminal amino acids and contains the conserved intein blocks A and B which are similar to the motifs found in the C-terminal autoprocessing domain of the hedgehog protein. The C-terminal splicing region is composed of the two conserved blocks F and G located in the about 50 C-terminal amino acids. Although, no single residue is invariant, the Ser and Cys in block A, the His in block B, the His, Asn and Ser/Cys/Thr in block G are the most conserved residues in the splicing motifs. Protein splicing requires neither cofactors nor auxiliary enzymes and involves a series of four intramolecular reactions in which several of these most conserved residues are implicated .

Resolution of the crystal structure of the Mxe GyrA mini-intein revealed a flattened 'horseshoe shaped' protein composed primarily of β-strands forming two homologous subdomains that are related by a pseudo twofold axis of symmetry. Despite a low level of sequence conservation, the two subdomains are nearly superimposable, suggesting that they could have arisen by tandem duplication of a primordial gene. However, the duplicated sequences do not correspond directly to the two subdomains as the two subdomains have exchanged homologous loop regions .

This entry represents the C-terminal splicing region that covers the intein blocks F and G. It extends to the first extein residue following the intein.
Phage portal protein PBSX family, Proteobacteria (PBSX_Proteobac)
Type: Family

This entry represents the phage-like element PBSX protein from Proteobacteria. PBSX protein forms a hole, or portal, that enables DNA passage during packaging and ejection. It also forms the junction between the phage head (capsid) and the tail proteins. It functions as a dodecamer of a single polypeptide of average molecular weight of 40-90kDa.
Putative nonproteinogenic amino acid hydroxylase (Nonproteo_OH)
Type: Family

This extremely rare protein family, a branch of the 2-oxoglutarate dependent oxygenase family related to proline 3-hydroxylase, appears only in natural product biosynthetic clusters that include nonribosomal peptide synthases. One members is PlyP from the polyoxypeptin A cluster, suggested to hydroxylate 3-methylproline. Another, GetF from the GE81112 biosynthetic gene cluster, is a proposed to hydroxylate pipecolic acid .
Hemophore Rv0203 (Hemophore_Rv0203)
Type: Family

Members of this family, including Rv0203 from Mycobacterium tuberculosis, are secreted heme-binding proteins used in heme acquisition. Such proteins are called hemophores. Members have a cleavable N-terminal signal peptide, and a mature region just over 100 amino acids long with a pair of invariant Cys residues. An unrelated hemophore, HasA, occurs in Gram-negative pathogens such as Yersinia pestis .
Acido-empty-quinoprotein group A (Acido_non_PQQ)
Type: Family

Members of this family closely resemble quinoproteins and quinohemoproteins such as PQQ-dependent methanol, glucose, and shikimate dehydrogenases, but restricted to species of Acidobacteria unable to synthesize PQQ. Seven members occur in Candidatus Solibacter usitatus Ellin6076, eleven in Acidobacteriaceae bacterium KBS 96, etc. Members have N-terminal signal sequences. They lack the pair of adjacent Cys residues, involved in electron transfer, typical for family

, and they lack CxxCH motifs for cytochrome c-like heme-binding. What cofactor these paralogous families of enzymes might use is unclear.
Uncharacterised protein MG279/MG280 (MG279/MG280)
Type: Family

Members of this family are uncharacterised proteins from the genus Mycoplasma, typically about 260 amino acids long, with a hydrophobic predicted transmembrane α helix toward each end. Often two family members are encoded in tandem, e.g. MG_279 and MG_280 from Mycoplasma genitalium.
Putative immunoglobulin-blocking virulence protein (Predic_Ig_block)
Type: Family

Members of this family are putative virulence proteins of Mycoplasma and Ureaplasma species. They share a region of sequence similarity (see

) with protein M, a Mycoplasma genitalium protein that binds a conserved light chain region of IgG and blocks its protective function of antigen-specific binding. Proteins in this entry contains an N-terminal signal-anchor domain and a proline-rich linker domain, and a C-terminal extension, in addition to the protein M-like domain recognised by

.
IgG-blocking virulence domain (Mycoplas_M_dom)
Type: Domain

This entry represents a domain found in Mycoplasma and Ureaplasma proteins. Proteins containing this domain include protein M of Mycoplasma genitalium, MG_281, a virulence protein that binds the IgG light chain to block the binding of antibody to antigen. The crystal structure of the protein M antibody-binding region that includes this domain is solved (

) . Full-length homologues to MG_281 are known in a few other Mycoplasma species, but this domain shows distant homology to many additional proteins with a much wider distribution across the Mollicutes. Proteins in this entry also include paralogous families in some species, such as MCAP_0345, MCAP_0347, MCAP_0349, and MCAP_0351 in Mycoplasma capricolum .
IgG-blocking protein M (M_MG281)
Type: Family

Members of this family, including MG_281 of Mycoplasma genitalium, bind conserved regions of the IgG light chain sequences, blocking IgG's normal function of antigen-specific binding. They are therefore important virulence proteins. Proteins in this entry contain a domain (

) shared by many other Mycoplasma and Ureaplasma proteins .