SII-SWORD/CoKE huggingface dataset:
Putative ATP-grasp target RiPP, Rhodococcus (GRASP_targ_2_Rhodococcus)
Type: Family

Members of this small family are putative RiPP (Ribosomally translated, Post-translationally modified Peptides) precursors, modified by RimK-like ATP-grasp proteins. Members are encoded near both an ATP-grasp protein and C39 peptidase domain-containing transporter. Members are short polypeptides that contain the GG motif expected for cleavage on export.
Radical SAM/SPASM domain peptide maturase, XyeB family (rSAM_SPASM_XyeB)
Type: Family

Members of this family are radical SAM/SPASM domain enzymes associated with maturation of the XyeA family of GG-motif containing RiPP (Ribosomally synthesised, Post-translationally modified Peptide) natural products. These enzymes crosslink the side chains of the first and third residues in motifs of three, one of which is Trp or Phe, to form strained aromatic cyclophane moieties .
RiPP peptide, XyeA family (RiPP_XyeA)
Type: Family

Members of this family are short polypeptides with a conserved GG motif as found in bacteriocins that are cleaved upon export. Each gene occurs immediately upstream of a gene for a peptide-modifying radical SAM/SPASM domain protein. The system is designated Xye for genera Xenorhabdus, Yersinia, and Erwinia, hence XyeA for the precursor peptide. The vicinity will also contain a transport protein with a C39 family peptidase domain (

), characteristic of GG motif cleave-on-export systems.
Cytochrome c-550, proteobacteria (c550_proteobact)
Type: Family

Members of this family are c-type cytochromes from proteobacteria with some remote similarity to the sulfur oxidation cytochrome SoxX . Cytochrome c550 is an essential component of the ethanol oxidation system that allows P.aeruginosa to grow on ethanol as the sole carbon and energy source. Is the direct electron acceptor of the quinoprotein ethanol dehydrogenase (QEDH) .
Bacterial microcompartment assembly protein PduM (PduM)
Type: Family

A bacterial microcompartment is a protein-based metabolic organelle where several enzymes and metabolites are brought together. PduM is a structural component of the microcompartments involved in coenzyme B(12)-dependent 1,2-propanediol degradation by Salmonella enterica .
Violacein biosynthesis protein VioB (VioB)
Type: Family

Following the action of a flavin-dependent L-amino acid oxidase that converts L-tryptophan to indole-3-pyruvate imine, the enzymes VioB (this family; also known as 2-imino-3-(indol-3-yl)propanoate dimerase,

), RebD, and StaD can ligate two molecules, forming a coupled iminophenyl-pyruvate dimer. In the violacein biosynthesis pathway, this compound is acted on by VioE before it cyclizes spontaneously to chromopyrrolic acid. In the pathways of homologue StaD (staurosporine), chromopyrrolate is formed, and the enzyme is referred to as chromopyrrolate synthase. RebD is very similar to StaD, but acts on chlorinated Trp-derived molecules .
Diol dehydratase reactivase ATPase-like domain (DDR_dom)
Type: Domain

Diol dehydratase (DDH,

) and its isofunctional homologue glycerol dehydratase (GDH,

) are enzymes which catalyse the conversion of glycerol 1,2-propanediol, and 1,2-ethanediol to aldehydes . These reactions require coenzyme B12. Cleavage of the Co-C bond of coenzyme B12 by substrates or coenzyme analogues results in inactivation during which coenzyme B12 remains tightly bound to the apoenzyme.
Thiosulfate oxidation carrier complex protein SoxZ (SoxZ)
Type: Family

SoxZ forms a heterodimer with SoxY, the subunit that forms a covalent bond with a sulfur moiety during thiosulfate oxidation to sulfate . Note that virtually all proteins that have a SoxY domain fused to a SoxZ domain are functionally distinct and not involved in thiosulfate oxidation.
Exosortase O (Exosort_XrtO)
Type: Family

Members of this family are a variant form of exosortase, XrtO, with a dedicated target typically encoded by the adjacent gene. Members have a unique C-terminal extension very different from EpsI (

), the extension that many exosortases have. The targets of XrtO all are members of the PEP-CTERM integral membrane protein family (

), which describes a PEP-CTERM protein about 950 residues long, found in more than 15 genera so far. These PEP-CTERM proteins are unusually hydrophobic in stretches, suggesting an integral membrane location, which is unusual. About one third of the members of IPR014270 are in genomes with this protein, exosortase O, always encoded by an adjacent gene.
SoxY-related AACIE arm protein (SoxY_para_1)
Type: Family

Members of this family are paralogues to the authentic thiosulfate oxidation system protein SoxY. True SoxY end with the sequence GGCG(G), the swinging arm in which the Cys residue covalently binds the inorganic sulfur moiety. In this family, members end with a different swinging arm sequence, [AS]AC[IVT]E. The few species with a member of this family always have authentic SoxY .
Thiosulfohydrolase SoxB (Thiosulf_SoxB)
Type: Family

SoxB, a di-manganese(II) enzyme, works with SoxYZ and the c-type cytochrome SoxXA in oxidation of thiosulfate to sulfate . SoxB has sequence similarity to the 5'-nucleotidase family of enzymes, which catalyse the hydrolytic cleavage of phosphate groups from nucleotides . This sequence similarity suggests that SoxB also carries out a hydrolytic reaction, probably the hydrolysis of a sulfur-sulfur bond, though this activity has not been demonstrated.
Sulfur oxidation c-type cytochrome SoxX (Thiosulf_SoxX)
Type: Family

Members of this family are SoxX, a c-type cytochrome with a CxxCH motif, part of a heterodimer with SoxA. SoxAX cytochromes play a key role in bacterial thiosulfate oxidation .

There are three distinct types of SoxAX proteins. Type I and II SoxAX proteins are heterodimers, while the heterotrimeric SoxAXK proteins form the third group. Type I SoxAX proteins have SoxA subunits with two heme groups and SoxX subunits with a molecular mass of approximately 14kDa, while the Type II SoxA proteins only contain one heme group, and are associated with SoxX proteins that have a molecular mass of approximately 20kDa. The increased molecular mass in these SoxX proteins is largely due to the presence of an N-terminal extension .
Proline reductase cluster protein PrdD (D_pro_red_PrdD)
Type: Family

PrdD is encoded in the proline reductase gene cluster. It is closely homologous to PrdA, which cleaves during maturation to create two subunits of the proline reductase complex, one of which has a Cys-derived pyruvoyl active site .
Proline reductase-associated electron transfer protein PrdC (PR_assoc_PrdC)
Type: Family

Members of this family are encoded near the prdA and prdB genes for proteins of the proline reductase complex. They are induced by proline, and have been designated as PrdC . Some members are selenoproteins (at two different positions), as is PrdB. Members are homologous to, but distinct from, electron transport protein RnfC .
D-proline reductase, PrdA proprotein (D_pro_red_PrdA)
Type: Family

Members of this family are the PrdA proprotein. The polypeptide undergoes an autocatalytic cleavage that creates two subunits, one with a Cys-derived pyruvoyl motiety critical for activity. The D-proline reductase complex also contains a subunit derived from the prdB gene . The complex acts on D-proline, which may be supplied from L-proline by an active proline racemase encoded nearby .
Radical SAM P-methyltransferase, PhpK family (BcpD_PhpK_rSAM)
Type: Family

Characterised members of this family are B12-binding domain/radical SAM domain enzymes that use methylcobalamin as a methyl donor to methylate a phosphorous atom during the biosynthesis of natural products such as bialaphos and phosalacine. These syntheses create an extremely rare C-P-C bond .
Radical SAM/CxCxxxxC motif protein YfkAB (rSAM_YfkAB)
Type: Family

Members of this family highly conserved in some Firmicutes have an N-terminal radical SAM domain (

) and a C-terminal domain (

) with a CxCxxxxC motif that suggests binding to an additional metallocluster. It appears all correct sequences in this family are about 370 amino acids in length, containing the YfkA and YfkB regions originally reported as separate ORFs in Bacillus subtilis. Partial Phylogenetic Profiling shows occurrences almost exclusively in the Bacilli, with very few examples of either lateral transfer or gene loss. The essentially monophyletic distribution suggests a housekeeping function. Members have no well-conserved gene neighbourhood. The function is unknown.
XrtN system VIT domain protein (Sorted_by_XrtN)
Type: Family

Members of this subfamily average about 850 amino acids in length, ending with a variant form of PEP-CTERM sorting signal. Members have a VIT (vault protein inter-alpha-trypsin inhibitor heavy chain) domain (

). Other bacterial subfamilies of VIT domain proteins have members with either GlyGly-CTERM or LPXTG C-terminal sorting signals. Members of this subfamily occur only in context next to a protein sorting/processing enzyme, exosortase N (XrtN). These subsystems occur both among the Bacteriodetes and in the spirochete genus Leptospira .
Exosortase N (Exosort_XrtN)
Type: Family

Members of this family are exosortase N (xrtN), a bacterial exosortase variant whose single target, encoded always by an adjacent gene, belongs to the vault protein inter-alpha-trypsin family. This system occurs in a number of spirochete (Leptospira) and Bacteriodetes species .
Phenylalanine aminomutase (D-beta-phenylalanine forming) (Phe_D_beta_mut)
Type: Family

Members of this family have the MIO prosthetic group (4-methylideneimidazole-5-one), derived from an Ala-Ser-Gly motif. Other MIO enzymes include Phe, Tyr, and His ammonia-lyases. The member from Pantoea agglomerans, and probably all members, convert Phe to D-beta-phenylalanine (

). By contrast, members of family

convert Phe to L-beta-phenylalanine (

), as in taxol biosynthesis .
Phenylalanine aminomutase (L-beta-phenylalanine forming) (Taxol_Phe_23mut)
Type: Family

Members of this family are the phenylalanine aminomutase known from taxol biosynthesis . This enzyme has the MIO prosthetic group (4-methylideneimidazole-5-one), derived from an Ala-Ser-Gly motif. Other MIO enzymes include Phe, Tyr, and His ammonia-lyases. This entry serves as an exception to overrule assignments by

for phenylalanine ammonia-lyase.
Three-Cys-motif partner protein (Tcm_partner)
Type: Family

Members of this family occur regularly as a partner to a member of family (

). Conserved motifs suggest enzymatic activity. Note that its frequent partner protein (

) has a three-cysteine motif that resembles the Cx3CxxC motif of radical SAM proteins, and that in one branch (

) actually becomes Cx3CxxC.
Radical SAM mobile pair protein A (rSAM_mob_pairA)
Type: Family

Members of this family are the upstream member (A) of a pair of tandem-encoded radical SAM enzymes. Most of these radical SAM gene pairs have an additional upstream regulatory gene in the MarR family. Examples of high sequence identity (over 96 percent) from cassettes in several Treponema species of the oral cavity to those in multiple Firmicutes in the gut microbiome suggest recent lateral gene transfer, as might be expected for antibiotic resistance genes. The function is unknown.
MarR family transcriptional regulator (Reg_MarR)
Type: Family

A number of human microbiome species from both the Firmicutes and the spirochete genus Treponema share a gene cassette encoding a pair of radical SAM enzymes and, in most cases, this MarR family transcriptional regulator as well. Sequence identity can exceed 96 percent, suggesting recent lateral transfer. These observations suggest the cassette confers resistance to a toxic compound such as an antibiotic.
Radical SAM mobile pair protein B (rSAM_mob_pairB)
Type: Family

Members of this family are the downstream member (B) of a pair of tandem-encoded radical SAM enzymes. Most of these radical SAM gene pairs have an additional upstream regulatory gene in the MarR family. Examples of high sequence identity (over 96 percent) from cassettes in several Treponema species of the oral cavity to those in multiple Firmicutes in the gut microbiome suggest recent lateral gene transfer, as might be expected for antibiotic resistance genes. The function is unknown.
CGA synthase-related protein (CGA_synth-rel)
Type: Family

Members of this family are related to cytosylglucuronate (CGA) synthase (

), and found in the same clusters as CGA synthase and CGA decarboxylase. These clusters produce peptidyl nucleoside antibiotics with a pyranoside core moiety, found in a number of Streptomyces species. Removal of the S. griseochromogenes member of this family, BlsF, from a heterologous expression system caused an increase, not blockage, of blasticidin S .
Cytosylglucuronate decarboxylase (rSAM_BlsE)
Type: Family

BlsE, part of the blasticidin S biosynthetic pathway, is a radical SAM enzyme that performs a decarboxylation at C5 of the glucoside residue. MilG in mildiomycin biosynthesis is equivalent. This enzyme follows CGA synthase and makes the pyranoside core moiety of a class of peptidyl nucleoside antibiotics .
Arginine 2,3-aminomutase (Arg_2_3_am_muta)
Type: Family

Members of this family are arginine 2,3-aminomutase, a radical SAM enzyme more closely related to lysine 2,3-aminomutase than to glutamate 2,3-aminomutase. The enzyme makes L-beta-arginine, sometimes in the context of antibiotic biosynthesis (blasticidin S, mildiomycin, etc). Activity is proven in Streptomyces griseochromogenes, which makes blasticidin S (Prabhakaran, et al., J. Am. Chem. SOC. 1988, 110. 5785-5791).
Hydroxymethylcytosylglucuronate/cytosylglucuronate synthase (CGA_synthase)
Type: Family

Members of this family synthesise cytosylglucuronate (or hydroxymethylcytosylglucuronate) from UDP-glucuronate and free cytosine (or hydroxymethylcytosine). This reaction is followed by a decarboxylation at C5 of the glucoside residue. The net reaction makes the pyranoside core moiety of a class of peptidyl nucleoside antibiotics .
TAT-translocated F420-dependent dehydrogenase, FGD2 family (F420_FGD2)
Type: Family

Members of this family are F420-binding enzymes with a proven functional N-terminal twin-arginine translocation (TAT) signal. Members are homologous to the cytosolic F420-dependent glucose-6-phosphate dehydrogenase but do not share the same function .
LipL41-expression chaperone Lep (Chaper_lep)
Type: Family

Members of this protein family are Lep, an outer membrane lipoprotein LipL41-binding protein that appears to function as a chaperone important to its expression. LipL41 is the third most abundant lipoprotein in the pathogen Leptospira interrogans, but is found in saprophytic Leptospira species as well and is not essential for virulence .
Radical SAM/SPASM domain protein maturase (rSAM_vs_C_rich)
Type: Family

Members of this family are probable protein/peptide-modifying radical SAM/SPASM domain proteins. The majority of members of this family seem to target Cys-rich repetitive regions of large proteins rather than of bacteriocin-sized small precursors. This arrangement suggests the modification target may be multifunctional, with the C-terminal domain behaving like a bacteriocin but other parts of the same precursor serving an immunity function, as occurs for the halocin C8 precursor.
Enduracididine biosynthesis enzyme MppP (Endura_MppP)
Type: Family

Members of this family are MppP, one of three enzymes involved in synthesizing enduracididine, a non-proteinogenic amino acid used in non-ribosomal peptide synthases to make natural products such as enduracidin from Streptomyces fungicidicus ATCC 21013. MppP is a PLP-dependent enzyme, predicted by homology to be an aminotransferase .
Enduracididine biosynthesis enzyme MppQ (Endura_MppQ)
Type: Family

Members of this family are MppQ, one of three enzymes involved in synthesizing enduracididine, a non-proteinogenic amino acid used in non-ribosomal peptide synthases to make natural products such as enduracidin from Streptomyces fungicidicus ATCC 21013. MppQ is a PLP-dependent enzyme, predicted by homology to be an aminotransferase .
Enduracididine biosynthesis enzyme MppR (Endura_MppR)
Type: Family

Members of this family are MppR, one of three enzymes involved in synthesizing enduracididine, a non-proteinogenic amino acid used in non-ribosomal peptide synthases to make natural products such as enduracidin from Streptomyces fungicidicus ATCC 21013. MppR belongs to the acetoacetate decarboxylase-like superfamily. MppR catalyses an aldol condensation and a dehydration, not a decarboxylation .
4-nitrotryptophan synthase (CYP450_TxtE)
Type: Family

Members of this family are cytochrome P450 enzymes that convert L-tryptophan into L-4-nitrotryptophan. In thaxtomin gene clusters, this enzyme (TxtE) uses nitric acid (NO) derived from arginine by the nitric oxide synthase TxtD, and O2, to perform the tryptophan nitration. L-4-nitrotryptophan is then used as a non-proteinogenic amino acid by non-ribosomal peptide synthases (NRPS) .
Lipoprotein LenA (Lipo_LenA_lepto)
Type: Family

Members of this family are LenA (Leptospira Endostatin-like protein A), found in pathogenic and intermediate species of Leptospira but not in saprophytes. LenA binds plasminogen, laminin, and complement regulator factor H. Behavior during outer membrane solubilisation by low concentrations of Triton X-114 and conservation in all family members of an apparent lipoprotein signal sequence, with invariant Cys residue, strongly suggest that LenA is a lipoprotein. Just outside this family is a full-length homologue found in another spirochete, Turneriella parva DSM 21527 .
LruC domain (LruC_dom)
Type: Domain

This domain is abundant in the Leptospira, in Bacteroides, and in Vibrio (three widely separated lineages). Most members have plausible lipoprotein signal peptides, including lipoprotein LruC from Leptospira interrogans and BACOVA_00967, from Bacteroides ovatus, with a solved crystal structure. Note that the C-terminal region of an uncharacerised domain (

) (length 83) matches the N-terminal region of some members of this domain (length 243) .
3-deoxy-D-manno-octulosonic acid transferase WaaZ (WaaZ_KDO_III)
Type: Family

This entry represents WaaZ, also known as Kdo-III transferase. This enzyme, present in some strains of E. coli and its allies but not others, performs a non-stoichiometric addition of a third 3-deoxy-D-manno-oct-2-ulosonic acid (KDO-III) onto some fraction of KDO-II in the lipopolysaccharide (LPS) inner core .
Probable lipoprotein, LA_1396/MXAN_6521 family (Lipo_MXAN_6521)
Type: Family

Members of this family are predicted lipoproteins, near 200 residues in length, found in multiple species of Leptospira (a spirochete) but also in the Myxococcales branch of the Deltaproteobacteria (Myxococcus xanthus, Chondromyces apiculatus, Cystobacter fuscus, Corallococcus coralloides), an uncommon mix of species. In both lineages, the N-terminal region appears to be a lipoprotein signal peptide.
Small lipoprotein, LB_250 family (Lepto_4Cys)
Type: Family

Members of this family average about 92 amino acids in length, including an apparent lipoprotein signal peptide and a mature portion with four additional invariant Cys residues. This family is universal, so far, across at least twenty species of Leptospira but unknown outside the genus.
Cys-rich protein, LA_1312 family (Lepto_8Cys)
Type: Family

Members of this protein family occur in the genus Leptospira. Members, although small (about 90 amino acids), have a predicted signal peptide followed by a region with eight invariant Cys residues. Some members have an additional Cys in the signal peptide region that suggests handling as a lipoprotein, but this Cys is not well conserved.
Small lipoprotein, LA_3946 family (Lepto_Lipo_YY_C)
Type: Family

This entry represents a group of small lipoproteins that occur in at least nineteen species of Leptospira, but not so far anywhere outside that genus. They have putative lipoprotein modification Cys and an additional Cys near the C terminus, both invariant, plus a well-conserved (although not invariant) Tyr-Tyr pair. From one to four paralogues occur in most Leptospira species.
Lantipeptide, SCO0268 family (Lanti_SCO0268)
Type: Family

Members of this family are putative lantipeptide (most likely lantibiotic) precursors, about 53 amino acids long, found in a lantibiotic-type biosynthetic cluster in several species of Streptomyces (S. coelicolor, S. griseoflavus, S. ambofaciens, etc.). This family is described in AntiSMASH as Streptomyces PEQAXS motif lantipeptide precursor .
Putative immunity protein/bacteriocin (Gpos_C8-like)
Type: Family

Proteins in this Gram-positive bacteria family consist of an N-terminal signal peptide, a central region of unknown function, and a Cys-rich C-terminal region. In both the overall architecture and the apparent weak homology of the C-terminal region itself, these proteins resemble archaeal proteins such as the halocin C8 precursor. In that precursor, the C-terminal region is a bacteriocin but the N-terminal region functions as the immunity protein. The related family of halocin C8-like bacteriocins and their bacterial homologues can be found in the halocin C8-like bacteriocin domain entry (

).
Halocin C8-like bacteriocin domain (Halocin_C8_dom)
Type: Domain

This entry represents the 76-amino C-terminal domain of the halocin C8 precursor that actually becomes the mature bacteriocin halocin C8 after export and cleavage, as well as homologous C-terminal regions from many other archaea. Surprisingly, this Cys-rich region occurs also in many strains of Staphylococcus epidermidis. Gene regions do not provide evidence for post-translational modification other than cleavage. Halocin C8 is active against a broad range of archaea; the region N-terminal to the bacteriocin domain modeled here serves as the immunity protein for the cell secreting the bacteriocin .
Creatinine amidohydrolase (Creatininase)
Type: Family

Creatinine amidohydrolase (also known as creatininase) is a cyclic amidohydrolase that catalyses the reversible conversion of creatinine to creatine .
Cyanobactin cluster PatC/TenC/TruC protein (PatC_TenC_TruC)
Type: Domain

Members of this family usually are small proteins (PatC, TenC, TruC) of unknown function in cyanobactin (prenylated cyclic peptide) biosynthesis clusters, where a different small protein is a known cyanobactin precursor (patellamide, anacyclamide, piricyclamide, etc). They may instead be the C-terminal domain of a longer protein that otherwise consists mostly of lectin-like or VWF type A domains, in similar context. Similar to the cyanobactin precursors, members of this family have two very strongly conserved regions separated by a hypervariable region, suggesting these proteins may undergo a similar maturation .
Prenylated cyclic peptide, anacyclamide/piricyclamide family (Pren_cyc_PirE)
Type: Family

Members of this protein family occur primarily in Cyanobacteria. They average about 50 residues in length and are the ribosomally translated precursors of peptide natural products whose modifications include cleavage, cyclization, and prenylation. Sequences are well-conserved in the N-terminal region. They are nearly invariant over the last eight residues, but hypervariable just before that stretch .

Cyanobactins are small, cyclic peptides found in cyanobacteria. They are ribosomally synthesised and post-translationally modified. Anaclyclamides are a type of cyanobactin produced in strains of the cyanobacteria Anabaena .

Anacyclamide synthesis protein AcyE is a 49-amino-acid protein with N-terminal homology to the peptide precursor proteins in the other cyanobactin pathways. The core peptide of AcyE is cleaved during post-translational processing of the precursor peptide .
Peptide O-prenyltransferase, LynF/TruF/PatF family (Preny_LynF_TruF)
Type: Family

Members of this family are prenyltransferases that modify mostly, perhaps exclusively, ribosomally derived cyclic peptides. Note that in some cases, the natural product becomes C-prenylated through a non-enzymatic rearrangement after initial O-prenylation. Prenylated products carry names such as prenylagaramide, anacyclamide, and piricyclamide .