SII-SWORD/CoKE huggingface dataset:
Thaumarchaeosortase (Thauma_sortase)
Type: Family

This member of the archaeosortase/exosortase family occurs exclusively in the Thaumarchaeota, where the corresponding proposed sorting signal is PEFG-CTERM (see

). This family is unusual in that the suspected active site residue, Cys in every other defined subfamily of archaeosortases and exosortases is replaced by Ser.
Histidine-histamine antiporter (His_histam_anti)
Type: Family

Members of this protein family are antiporters that exchange histidine with histamine, product of histidine decarboxylation. A system consisting of this protein, and a histidine decarboxylase encoded by an adjacent gene, creates decarboxylation/antiport proton-motive cycle that provides a transient resistance to acidic conditions .
Pyridoxal-phosphate-dependent protein EgtE (EgtE)
Type: Family

Members of this protein family are the pyridoxal phosphate-dependent enzyme EgtE, which catalyzes the final step in the biosynthesis of ergothioneine .
Hopanoid C-3 methylase HpnR (HpnR_B12_rSAM)
Type: Family

Members of this are family are a B12-binding domain/radical SAM domain protein required for 3-methylhopanoid production . Activity was confirmed by mutant phenotype by disrupting this gene in Methylococcus capsulatus strain Bath. This protein family should only occur in genomes that encode a squalene-hopene cyclase.
Cupin fold metalloprotein, WbuC family (Cupin_WbuC)
Type: Family

Members of this family show sequence similarity to cupin fold proteins, including conserved His residues likely to serve as metal-binding ligands. Many members occur in bacterial O-antigen biosynthesis regions . Some members have acquired the gene symbol wbuC, but publications using this term do not ascribe a function.
Putrescine transporter PotE (Symport/antiport_PotE)
Type: Family

Members of this protein family are putrescine-ornithine antiporters . They work together with an enzyme that decarboxylates ornithine to putrescine. This two-gene system has the net effect of removing a protein from the cytosol, providing transient resistance to acid conditions . They can function not only as a putrescine-ornithine antiporters to excrete putrescine but also as a putrescine uptake proteins .
Exosortase XrtM (Exosort_XrtM)
Type: Family

Members of this family, part of the larger exosortase/archaeosortase family, are known from five related cassettes of genes in Methylomonas methanica MC09, a gammaproteobacterial methanotroph. Each xrtM gene occurs near a large YD repeat (see

) protein of 1500-2500 residues and a small, uncharacterised protein of about 200 residues. No PEP-CTERM-like recognition sequence has been identified, so this protein is designated as exosortase family, but not necessarily a functional exosortase.
Ornithine decarboxylase SpeF (ODC_inducible)
Type: Family

Members of this family are known or trusted examples of ornithine decarboxylase, all encoded in the immediate vicinity of an ornithine-putrescine antiporter . Decarboxylation of ornithine to putrescine, followed by exchange of a putrescine for a new ornithine, is a proton-motive cycle that can be induced by low pH and protect a bacterium against transient exposure to acidic conditions .
GeoRSP system PqqD family protein (Geo_PqqD_fam)
Type: Family

Members of this PqqD-related family so far occur only in the genus Geobacter, always together with a PqqE-like radical SAM domain/SPASM domain protein and a second SPASM domain protein with traces of a degenerate radical SAM domain. The extended gene region includes a high-molecular-weight cytochrome c family protein. Besides authentic PqqD (

), another example of a PqqD family protein occurs in the SynChlorMet cassette, again with two PqqE-like proteins. The system is named GeoRSP for its prevalence in Geobacter, its Radical SAM protein, is SPASM domain protein, and its PqqD family protein.
GeoRSP system radical SAM/SPASM protein (GeoRSP_rSAM)
Type: Family

Members of this family are radical SAM/SPASM domain proteins from a cassette restricted to the genus Geobacter. Genes always found adjacent include a non-radical SAM protein with a closely related SPASM domain and a short stretch of N-terminal homology as well to this family, and also a PqqD-like protein. The three-gene cassette is designated GeoRSP for the genus Geobacter, this radical SAM protein, the SPASM domain protein, and the PqqD family protein.
GeoRSP system SPASM domain protein (GeoRSP_SPASM)
Type: Family

Members of this protein family are encoded by one of two consecutive genes for SPASM domain proteins. The two are closely homologous in the SPASM domain regions, and also in a small N-terminal region, but the other family (

) has an intact radical SAM domain (

) that this "quasi-rSAM" protein lacks. A PqqD-family protein,

, is always adjacent.
4-aminobenzoate synthase (Fol-rel_CADD)
Type: Family

This protein family includes the well-studied Chlamydia protein CADD (Chlamydia protein Associating with Death Domains), which is involved in the biosynthesis of para-aminobenzoate (pABA), an essential component of the folate cofactor that is required for the survival and proliferation of the human pathogen Chlamydia trachomatis . It can induce apoptosis in a host cell . Other members of this family occur in Rickettsia and Wolbachia, unrelated in terms of phylogeny (both are alphaproteobacteria) but similar in living intracellularly .
Methyltransferase, FxLD system (Methyltran_FxLD)
Type: Family

Members of this family resemble occur regularly in the vicinity of lantibiotic biosynthesis enzymes and their probable target, the FxLD family of putative ribosomal natural product precursor (

). Members resemble protein-L-isoaspartate O-methyltransferase (

)
and a predicted methyltranserase, (

), of another putative peptide modification system.
Thiaminase II (Thiaminase_II)
Type: Family

The TenA protein of Bacillus subtilis and Staphylococcus aureus , and the C-terminal region of trifunctional protein Thi20p from Saccharomyces cerevisiae , perform cleavages on thiamine and related compounds to produce 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP), a substrate of a salvage pathway for thiamine biosynthesis. The gene symbol tenA, for Transcription ENhancement A, reflects a misleading early characterisation as a regulatory protein. This family is related to PqqC from the PQQ biosynthesis system

, heme oxygenase

, and CADD (Chlamydia protein Associating with Death Domains), a putative folate metabolism enzyme

.
FxLD family lantipeptide (LD_lanti_pre)
Type: Family

Members of this protein family occur with a cassette of lanthionine-type peptide modification enzymes. Members are small (about 60 amino acids long), rich in Cys, and variable in copy number per genome (from one to three). These features suggest that members of this family are modified to become lantipeptides, although not necessarily a lantibiotic. There is no GlyGly cleavage motif to separate a leader peptide from core region.The considerable abundance in Streptomyces and relatively strong consideration hints at a non-antibiotic function. The motif FxLD in the N-terminal region is nearly invariant.
Choice-of-anchor C domain (Choice_anch_C_dom)
Type: Domain

This entry represents an extracellular bacterial domain that occurs on a number of proteins with PEP-CTERM (exosortase recognition site) sequences at the C terminus, as well some with an apparent alternate anchor sequence.
5-histidylcysteine sulfoxide synthase (OvoA_Nterm)
Type: Family

Ovothiol A is N1-methyl-4-mercaptohistidine. In the absence of S-adenosylmethione, a methyl donor, the intermediate produced is 4-mercaptohistidine. In both Erwinia tasmaniensis and Trypanosoma cruzi, a protein occurs with 5-histidylcysteine sulfoxide synthase activity, but these two enzymes and most homologues share an additional C-terminal methyltransferase domain. Thus OvoA may be a bifunctional enzyme with 5-histidylcysteine sulfoxide synthase and 4-mercaptohistidine N1-methyltranferase activity. This entry describes the 5-histidylcysteine sulfoxide synthase domain, a homologue of the ergothioneine biosynthesis protein EgtB .
Proline-rich tail region repeat (ProTail_Rpt)
Type: Repeat

This entry describes a proline-rich tandem repeat of about 24 residues found in C-terminal regions of Gram-positive surface proteins with LPXTG sequences for processing and cell surface attachment by sortase.
Surface protein repeat SSSPR-51 (SSSPR51_Rpt)
Type: Repeat

This repeat domain is designated SSRS51, Streptococcal and Staphylococcal Surface Protein Repeat of size 51. Up to twelve tandem repeats can occur, on some of the longest proteins of their respective species. Nearly all member proteins carry the C-terminal sortase target sequence, LPXTG. The repeat structure and probable surface location suggest a possible adhesion function. A protein with this class of repeats may have other classes as well.
EXLDI protein (EXLDI)
Type: Family

The most conserved region in this protein family is the C-terminal pentapeptide, with motif ExLDI. Members from the Firmicutes average about 120 amino acids in length, while members from the Actinobacteria have an additional 45-residue amino-terminal segment. It is suggested that the member from Streptococcus mutans UA159, and its homologs, participate in bacteriocin production, export, or immunity .
ACGX-repeat peptide (Target_ACGX)
Type: Family

Members of this family average 75 amino acids in length and average six instances of the motif ACGX, where X is A, S, or T. Members are proposed target sequences for modification by adjacent radical SAM/SPASM domain proteins (family TIGR04340). Cys residues adjacent to Gly residues are common as proposed sites for modification by radical SAM enzymes.
Amanitin/phalloidin toxin (Amanitin/phalloidin)
Type: Family

Members of this family are ribosomally produced precursors of toxins produced by several mushrooms. These precursors undergo extensive post-translational modification to become amatoxins (e.g. alpha-amanitin) and phallotoxins (e.g. phalloidin) . They are members of the MSDIN fungal toxin family .
Radical SAM/SPASM domain protein, ACGX system (rSAM_ACGX)
Type: Family

Members of this protein family are radical SAM/SPASM domain proteins likely to be involved in the modification of small, Cys-rich peptides. Members of the family of proposed target sequences,

, average 75 amino acids in length and average six instances of the motif ACGX, where X is A, S, or T.
Entry exclusion lipoprotein TrbK (TrbK_RP4)
Type: Family

The characterised model example of TrbK, from incompatibility group P (IncP) plasmid RP4, is an N-terminally processed lipoprotein, localized to the periplasmic face of the plasma membrane. TrbK prevents entry through conjugation by other IncP plasmids . Unrelated, uncharacterised proteins encoded in equivalent positions in other plasmid P-type conjugative transfer regions (e.g.

) may have analogous functions.
Pantocin A family RiPP precursor (Pantocin_A_RiPP_pre)
Type: Family

Members of this family are ribosomally-synthesised and posttranslationally-modified peptide (RiPP) precursors about 30 amino acids in length encoded in the vicinity of PaaA and PaaB homologues. Members include PaaP from Pantoea agglomerans, whose central tripeptide EEN appears to be the source of the mature product, pantocin A. Note, however, that the corresponding residues in Photobacterium sp. SKA34 and Photobacterium asymbiotica are EEK rather than EEN. This family, therefore, resembles the PQQ precursor PqqA as a peptide precursor of an extremely small mature product.
Putative radical SAM/SPASM metalloenzyme maturase (rSAM_metal_mat)
Type: Family

This entry describes a family of radical SAM/SPASM enzymes largely from the deltaproteobacteria. The family is most closely related to a radical SAM enzyme family regularly in archaea in the vicinity of tungsten-containing oxidoreductases. A single member of the family in archaea may correspond to multiple tungsten enzymes, e.g. five in Pyrococcus furiosus. Therefore, the lack of a conserved gene neighbourhood for members of this family in deltaprotebacteria suggests members may be involved in the maturation of multiple metalloenzymes.
Conjugative transfer region protein TrbK (TrbK)
Type: Family

Members of this family regularly are encoded between the TrbJ and TrbL proteins essential for P-type conjugal transfer, and therefore are designated TrbK. Positional analogy to family

(the entry exclusion lipoprotein TrbK of IncP plasmid RP4), which is a lipoprotein and not homologous, suggests this protein may also be involved in entry exclusion. Members of this family are small, with a non-lipoprotein signal peptide and a conserved disulfide bond.
XXXCH domain family (XXXCH_dom_fam)
Type: Family

Members of this family show C-terminal sequence similarity, perhaps indicating distant homology, to cytochrome c-prime (see

). However, the motif CxxCH is replaced by xxxCH. Genes for this protein occur in a sporadically distributed genome context, largely in deltaProteobacteria, in which an ATP-grasp family glutamate ligase homologue and a CofD (LPPG:FO 2-phospho-L-lactate transferase) homologue suggest a novel biosynthesis.
Choice-of-anchor B domain (Choice_anch_B)
Type: Domain

This domain, about 385 amino acids long, can have either of at least two types of C-terminal sorting signal. Members from Shewanella and allies have the rhombosortase target domain GlyGly-CTERM (

), while members of the Bacteroidetes have the Por secretion system C-terminal domain (

). Most other members lack any C-terminal extension, but in most of those, the normal signal sequence is replaced by a lipoprotein signal sequence. Member sequences show a region of local similarity to the LVIVD repeat sequence (

).
MSMEG_3727, PQQ-associated (PQQ_MSMEG_3727)
Type: Family

Members of this protein family are restricted to members of the Actinobacteria (Mycobacterium smegmatis, Streptomyces hygroscopicus, Geodermatophilus obscurus, Pseudonocardia dioxanivorans, Saccharomonospora marina, etc) that synthesize PQQ. These are small proteins, 155 amino acids long on average, found regularly next to a much larger protein, a PQQ-dependent oxidoreductase, and might be a companion subunit or an accessory protein such as chaperone involved in cofactor insertion.
CofD-related protein, GAK system (CofD-rel_GAK)
Type: Family

Members of this family are distantly related to CofD, the enzyme LPPG:FO 2-phospho-L-lactate transferase, involved in coenzyme F420 biosynthesis. This family appears to belong to a biosynthesis cassette of unknown function.
ATP-grasp enzyme, GAK system (ATP-grasp_GAK)
Type: Family

Members of this family are ATP-grasp family enzymes related to a number of characterised glutamate ligases, including the ribosomal protein S6 modification enzyme RimK. This group belongs to a conserved gene neighbourhood that also features an HPr kinase-related protein. We assign this system the initial designation GAK, for Grasp (this ATP-grasp family enzyme), Amphipathic (for the member of the domain entry

, designated Amphi-Trp), and Kinase, for the HPr-kinase homologue

.
Aromatic cluster surface protein (Aro_clust)
Type: Family

Members of this family are absolutely restricted to the Mollicutes (Mycoplasma and Ureaplasma). All have a signal peptide, usually of the lipoprotein type, suggesting surface expression. Most members have lengths of about 280 residues but some members have a nearly full-length duplication. The mostly nearly invariant residue, a Trp,is part of a strongly conserved 9-residue motif, [ND]-W-[LY]-[WF]-X-[LF]-X-N-[LI], where X usually is hydrophobic. Because the hydrophobic six-residue core of this motif almost always contains three to four aromatic residues, this family was called aromatic cluster surface protein. Multiple paralogues may occur in a given Mycoplasma, usually clustered on the genome.
Methanogenesis multiheme c-type cytochrome (Methanoheme_cyt)
Type: Family

Members of this protein family are multiheme cytochrome c proteins of Methanosarcina acetivorans C2A and several other archaeal methanogens. All members have N-terminal signal peptides and are presumed to act in electron transfer reactions associated with methanogenesis. Putative heme-binding motifs include five (or six) CXXCH motifs, a CXXXCH motif, and a CXXXXCH motif. These proteins show multiple regions of local homology, in the same order, with multiheme cytochrome c proteins such as octaheme tetrathionate reductase from Shewanella.
Conserved hypothetical protein CHP04338 (CHP04338)
Type: Family

This protein family is restricted to the Actinomycetales, including Mycobacterium, Rhodococcus, Nocardia, Gordonii, and others. The invariant motif HEXXH, at the core of the best conserved region in the protein, suggests metallohydrolase activity, as does local sequence similarity in this region to other metallohydrolases.
AmmeMemoRadiSam system radical SAM enzyme (AmmeMemoSam_rS)
Type: Family

Members of this protein family are uncharacterised radical SAM enzymes that occur in a prokaryotic three-gene system along with homologs of mammalian proteins Memo (Mediator of ErbB2-driven cell MOtility) and AMMERCR1 (Alport syndrome, Mental Retardation, Midface hypoplasia, and Elliptocytosis). Among radical SAM enzymes that have been experimentally characterised, the most closely related in sequence include activases of pyruvate formate-lyase and of benzylsuccinate synthase.
HprK-related kinase B (HprK-rel_B)
Type: Family

Members of this protein family resemble (and often are misannotated as) HprK, the serine kinase/phosphatase of the phosphocarrier protein HPr. However, members do not occur with an HPr homologue, but instead as part of a distinctive gene cassette of unknown function.
Amphi-Trp domain (Amphi-Trp_dom)
Type: Domain

This domain usually comprises most of the span of bacterial or archaeal proteins with a length of about 90 amino acids. Some members, however, are extended by one or two copies of domain

in the C-terminal region. No residue in this domain is invariant. A striking feature of this domain is a C-terminal region that alternates strongly charged with strongly hydrophobic residues and usually ends with a Trp residue, e.g. LEIEIEW or FEIKVRW, suggesting an amphipathic β-strand structure, therefore, the suggested the name for this domain is amphi-Trp. The function is unknown.
PqqD family protein, HPr-rel-A system (PqqD-rel_X)
Type: Family

Members of this protein show distant homology to PqqD, and belong to a three-gene cassette that included the HPr kinase related protein family of

. The role of the cassette, and of this protein, are unknown.
HprK-related kinase A (HprK-rel_A)
Type: Family

A number of protein families resemble HPr kinase (see

) but do not belong to that system. They include this family, which appears instead to be the marker for a different type of gene neighbourhood, in which one of the conserved neighbouring proteins resembles (but is distinct from) PqqD.
Cys-rich peptide, Clo7bot family (Clo7Bot_mod_Cys)
Type: Family

Members of this protein family range in size from 34 to 53 residues, including from four to seven Cys residues. Multiple strains of Clostridium botulinum show seven tandem members upstream of a radical SAM/SPASM domain protein likely to act as a ribosomal natural product maturase. By analogy to subtilosin A, the Cys residues are likely targets for modifications that may introduce new crosslinks. Across multiple strains of Clostridium botulinum and C. sporogenes, the adjacent radical SAM enzyme is nearly invariant.
Poly-gamma-glutamate system protein (PGA_system)
Type: Family

Poly(gamma-glutamic acid), or PGA, is an extracellular structural polymer found in Bacillus subtilis and a number of other species. PGA is sometimes capsule-forming, sometimes secretory, and may be produced by Gram-positive (single plasma membrane) and Gram-negative (inner and outer membranes) bacteria, so export and/or attachment machinery may differ from system to system. Members of this family occur in a subset of PGA operons, in lineages that include Francisella, Leptospira, Treponema, Thermotoga, Fusobacterium, and Clostridium, amongst others.
LIC12162 family transferase (LIC12162)
Type: Family

This protein family shows C-terminal sequence similarity to various surface carbohydrate biosynthesis enzymes: spore coat polysaccharide biosynthesis protein SpsB, UDP-N-acetyl-D-glucosamine 2-epimerase, lipid A disaccharide synthetase LpxB, etc. It may occur in O-antigen biosythesis regions.
Tungsten cofactor oxidoreducase radical SAM maturase (W_rSAM_matur)
Type: Family

Members of this family are radical SAM enzymes involved in the maturation of tungsten (W)-containing cofactors in the enzymes aldehyde ferredoxin oxidoreductase, formaldehyde ferredoxin oxidoreductase and others; and tend to be encoded by an adjacent gene .
Putative ornithine decarboxylase, Lactobacillus (Lacto_ODC_put)
Type: Family

In at least ten species of Lactobacillus, this close homologue to known ornithine decarboxylase occurs in a three-gene neighbourhood, along with an amino acid permease family transporter and pyridoxal phosphate-dependent enyzme from the cystathionine gamma-lyase family. Species include L. acidophilus, L. amylovorus, L. crispatus, L. delbrueckii, L. farciminis, L. helveticus, L. johnsonii, etc. The combination of a decarboxylase with an antiporter in a two-gene system suggests a decarboxylation/antiport proton-motive cycle for transient resistance to acidic conditions. The substrate for this decarboxylase might be ornithine but is unknown.
Surface protein repeat Ser-Ala-175 (SerAla_Lrha_rpt)
Type: Repeat

This serine and alanine-rich surface protein repeat, about 175 amino acids long, occurs up to nine times in surface proteins of some Lactobacillus strains. Members proteins have the N-terminal variant signal sequence described by

and C-terminal LPXTG signals for surface attachment by sortase.
SEC10/PgrA surface exclusion domain (Surf_Exclu_SEC10/PgrA)
Type: Domain

This entry represents a conserved domain found in surface proteins of a number of Firmicutes. Many members have LPXTG C-terminal anchoring motifs and a substantial number have the KxYKxGKxW putative sorting signal at the N terminus. The tetracycline resistance plasmid pCF10 in Enterococcus faecalis promotes conjugal plasmid transfer in response to sex pheromones, but PgrA/Sec10 encoded by that plasmid, a member of this family, specifically inhibits the ability of cells to receive homologous plasmids. The phenomenon is called surface exclusion .
Spirochetes SPASM protein (Spiro_SPASM)
Type: Family

This three-domain protein is restricted to the spirochetes and widely distributed (excepting Borrelia). It has a conserved C-terminal SPASM domain, a 4Fe-4S binding domain shared by a number of peptide-modifying and heme-modifying radical SAM proteins. It has a central radical SAM domain, although half the members have lost the signature 4Fe-4S-binding Cys residues, fail to register with the radical SAM domain definition of model in entry

, and must be considered pseudo-SAM proteins. PSI-BLAST shows a relationship between the N-terminal domain and various predicted glycosyltransferases (e.g. Bacillus subtilis SpsF) and cytidyltransferases. In some Treponema species, this protein appears to split into two tandem genes.
7-carboxy-7-deazaguanine synthase, proteobacteria (rSAM_QueE_proteobac)
Type: Family

This entry represents a group of prokaryotic radical SAM enzymes involved in the biosynthesis of queuosine, including 7-carboxy-7-deazaguanine synthase from Escherichia coli (QueE) . QueE is involved in making preQ0 (7-cyano-7-deazaquanine), a precursor of both the bacterial/eukaryotic modified tRNA base queuosine and the archaeal modified base archaeosine. Members of this family occur in species that lack known forms of QueE, but usually are not found in queuosine biosynthesis operons.
Sporadic carbohydrate cluster protein LIC12192 (SpoChClust_LIC12192)
Type: Family

Members of this uncharacterised protein family mark a rare but widely distributed carbohydrate biosynthesis cluster found sporadically in genera Bradyrhizobium, Leptospira, Magnetospirillum, Oscillatoria, Prochlorococcus, etc.