SII-SWORD/CoKE huggingface dataset:
Helix-rich protein (Mplasa_alph_rch)
Type: Family

Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely α-helical. These sequences show strong periodicity (consistent with long α helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.
Putative energy coupling factor transporter S component (EcfS_MSC_0063)
Type: Family

This family of proteins is restricted to the Mollicutes. Members belong to a superfamily of multiple membrane-spanning proteins, among which those with assigned activities function as the S component (the specificity component) of ECF transporters. However, members of this family are not recognised by other entries for S component proteins (

).
Energy-coupling factor transporter ATP-binding protein EcfA2 (EcfA2)
Type: Family

EcfA2 is an ATP-binding (A) component of a common energy-coupling factor (ECF) transport systems . It shares homology with the ATP-binding cassette (ABC) protein .

ECF transporters usually contain two ATPase subunits (or a double-length fusion protein), a T component, and a substrate capture (S) component that is highly variable, and may be interchangeable in genomes with only one T component.
ECF transporters can be classified into two groups: group I includes transporters that have a dedicated AT module encoded in the same gene cluster as an S component, while group II employs a universal energy-coupling module (EcfAA'T) that is encoded by a separate gene cassette and shared by many different unlinked S components. Group II is ubiquitous in the phyla Firmicutes and Thermotogales and also occurs in some members of the Archaea .
Energy-coupling factor transporter ATP-binding protein EcfA1 (EcfA_1)
Type: Family

EcfA1 is an ATP-binding (A) component of a common energy-coupling factor (ECF) transport systems . It shares homology with the ATP-binding cassette (ABC) protein .

ECF transporters usually contain two ATPase subunits (or a double-length fusion protein), a T component, and a substrate capture (S) component that is highly variable, and may be interchangeable in genomes with only one T component.
ECF transporters can be classified into two groups: group I includes transporters that have a dedicated AT module encoded in the same gene cluster as an S component, while group II employs a universal energy-coupling module (EcfAA'T) that is encoded by a separate gene cassette and shared by many different unlinked S components. Group II is ubiquitous in the phyla Firmicutes and Thermotogales and also occurs in some members of the Archaea .
TAT-variant-translocation signal domain (TAT_var_transloc_signal_dom)
Type: Domain

This entry represents a forty-five residue domain in which the last six residues represent the start of a TAT (Twin-Arginine Translocation) sorting signal. TAT allows proteins already folded, with cofactor already bound, to transit the membrane and reach the periplasm with the ability to perform redox or other cofactor-dependent activities. TAT signals are not normally seen so far from a well-supported start site. Proteins containing this domain may all be mutually homologous, with both a molybdenum cofactor-binding domain and a 4Fe-4S dicluster-binding domain .
ECF transporter S component, folate family (ECF_S_folate_fam)
Type: Family

This entry represents the multiple membrane-spanning S (specificity) component of ECF (energy coupling factor) transporters. This entry includes Lactobacillus casei FolT, which is a folate-binding protein . Several members were found in the vicinity of the bifunctional enzyme folC, involved in making active cofactor from imported folate. However, some species have multiple members of this family, suggesting some diversity of function.

ECF transporters usually contain two ATPase subunits (or a double-length fusion protein), a T component, and a substrate capture (S) component that is highly variable, and may be interchangeable in genomes with only one T component.
ECF transporters can be classified into two groups: group I includes transporters that have a dedicated AT module encoded in the same gene cluster as an S component, while group II employs a universal energy-coupling module (EcfAA'T) that is encoded by a separate gene cassette and shared by many different unlinked S components. Group II is ubiquitous in the phyla Firmicutes and Thermotogales and also occurs in some members of the Archaea .
Radical SAM family RiPP maturation amino acid epimerase (rSAM_PoyD)
Type: Family

This entry represents PoyD and its homologues. These are divergent putative radical SAM enzymes, with the classical CxxxCxxC motif but not found in

. PoyD appears responsible for catalysing a unidirectional L-to-D epimerization of 18 the 48 residues in the core peptide of the first characterised polytheonamide. The RiPP (ribosomally translated natural product) precursor, and peptides encoded near many other members of this family, belong to the nitrile hydratase leader peptide (NHLP) family .
Sec region non-globular protein (Sec_Non_Glob)
Type: Family

Members of this family occur only in the genus Leptospira, always encoded between genes for the YajC and SecD components of the Sec preprotein translocase. Sequences have an N-terminal signal peptide and a C-terminal transmembrane segment. Between these are regions of non-globular, low-complexity sequence including Lys-rich and Ser/Thr/Asn/Glu-rich regions.
FemAB family protein (FemAB)
Type: Family

Members of this family are FemA/FemB family proteins from a cassette that some Leptospira have in their O-antigen biosynthesis regions and share with a cassette from gamma proteobacterium IMCC1989.
Glycosyltransferase, activator-dependent family (Glycosyl_450act)
Type: Family

Many biosynthesis clusters for secondary metabolites feature a glycosyltransferase gene next to a P450 homologue, often with the P450 lacking a critical heme-binding Cys. These P540-derived sequences seem to be allosteric activators of glycosyltransferases such as the member of this family. This entry represents a set of related glycosyltransferases, many of which can be recognised as activator-dependent from genomic context. Proteins in this entry include:

3-alpha-mycarosylerythronolide B desosaminyl transferase eryCIII from Saccharopolyspora erythraea. It catalyzes the conversion of alpha-L-mycarosylerythronolide B into erythromycin D in the erythromycin biosynthesis pathway .

Aclacinomycin-T 2-deoxy-L-fucose transferase AknK from Streptomyces galilaeus. It is involved in the biosynthesis of the trisaccharide moiety characteristic of the antitumor drug aclacinomycins .

Aklavinone 7-beta-L-rhodosaminyltransferase AknS from Streptomyces galilaeus. It is involved in the biosynthesis of the anthracycline antitumor agent aclacinomycin A .

Tylactone mycaminosyltransferase from Streptomyces fradiae. It is involved in the biosynthesis of the macrolide antibiotic tylosin derived from the polyketide lactone tylactone .

Erythronolide mycarosyltransferase EryBV from Saccharopolyspora erythraea. It is involved in the biosynthesis of the macrolide antibiotic erythromycin .

TDP-daunosamine transferase DnrS from Streptomyces peucetius. It is involved in the biosynthesis of the anthracyclines carminomycin and daunorubicin (daunomycin) which are aromatic polyketide antibiotics that exhibit high cytotoxicity and are widely applied in the chemotherapy of a variety of cancers .
Putative PLP-dependent aminotransferase (PLP_IMCC1989)
Type: Family

Members of this family are PLP-dependent enzymes, probable aminotransferases of the DegT/DnrJ/EryC1/StrS family. Members occur in some Leptospira in their O-antigen biosynthesis regions and in a related cassette in gammaproteobacterium IMCC1989.
CRISPR type III-associated protein, CHP04423 family (CHP04423)
Type: Family

Members of this protein family occur only in species with CRISPR systems, in the context of type III systems that resemble type III-A (MTUBE) and III-B (the RAMP module). It occurs in several species of Prevotella, Helicobacter, Campylobacter, and Bacteroides.
Microcin B17-processing protein McbB (McbB)
Type: Family

This family includes zinc metalloprotein McbB, part of the maturase system for microcin B17, a thiazole/oxazole-modified microcin (TOMM). Other members of this family belong to very different gene neighbourhoods. The Cys residues that act as zinc ligands are conserved in most members, but for rare members are jointly absent .
AroB-related putative sugar phosphate phospholyase (cyclising) (Put_AroB)
Type: Family

Members of this family tend to be found in O-antigen biosynthesis regions. Members frequently are misidentified as the closely related 3-dehydroquinate synthase, AroB (see

), the phospholyase that converts 3-deoxy-D-arabino-hept-2-ulosonate 7-phosphate to 3-dehydroquinate
P450-derived glycosyltranferase activator (P450-rel_GT_act)
Type: Family

Members of this family resemble cytochrome P450 by homology, but lack a critical heme-binding Cys residue. Members in general are encoded next to a glycosyltransferase gene in a natural products biosynthesis cluster, physically interact with it, and help the glycosyltransferase achieve high specificity while retaining high activity. Many members of this family assist in the attachment of a sugar moiety to a natural product such as a polyketide . This entry includes Streptomyces venezuelae DesVII and its homologues, such as OleP1 from the oleandomycin-producing
Streptomyces antibioticus, DnrQ from the doxorubicin-producing Streptomyces peucetius, and TylMIII from the tylosin-producing Streptomyces fradiae .
GWxTD domain (GWxTD_dom)
Type: Domain

This domain, about 100 amino acids long, occurs in little studied Gram-negative bacteria, Sec-dependent proteins, 300-800 in length. The domain is rich in aromatic residues, with Trp, Tyr, or Phe as the majority amino acid in ten of the twenty-four most-conserved residue positions.
3-dehydroquinate synthase, N-terminal domain (DHQS/DOIS_N)
Type: Domain

This is the Rossmann-fold domain found at the N-terminal of these proteins, which binds NAD+ in an inverted orientation to that observed in all other classic Rossmann-fold proteins .

The 3-dehydroquinate synthase (DHQS) domain can exist in isolation or as a domain in the pentafunctional AROM polypeptide (

) . 3-dehydroquinate synthase catalyses the formation of dehydroquinate (DHQ) and orthophosphate from 3-deoxy-D-arabino heptulosonic 7 phosphate . This reaction is part of the shikimate pathway which is involved in the biosynthesis of aromatic amino acids. DHQS consists of an N-terminal Rossmann-fold domain and a C-terminal α-helical domain. The active site is located in a cleft between the two domains.

The enzyme 2-deoxy-scyllo-inosose synthase (DOIS) catalyses carbocycle formation from D-glucose-6-phosphate to 2-deoxy-scyllo-inosose through a multistep reaction, and is evolutionarily related to DHQS .
VPAMP-CTERM protein sorting domain (VPAMP_C)
Type: Domain

This domain is found as the extreme C-terminal region of four extracellular protein (mostly protease) precursor sequences in Chthoniobacter flavus Ellin428,
STREFT protein (Mycopla_NOT_gsn)
Type: Family

Members of this family occur strictly in the genus Mycoplasma, average 1050 in length with little length variability, have an N-terminal signal sequence, and exhibit no detectable sequence similarity to any characterised protein. Up to four tandem copies occur in some Mycoplasma (e.g. M. putrefaciens KS1). Incorrect inclusion of a 57-amino acid stretch of one family member in

, for a helix-turn-helix transcriptional regulator in several E. coli phage, has caused many members of this family to be annotated, in error, as GnsA/GnsB family proteins. The name STREFT (Secreted Thousand Residue Frequently Tandem) protein was suggested by TIGRfam as a distinctive name to spread and replace the incorrect GnsA/GnsB designation.
3-dehydroquinate synthase family (DHQ_synth_fam)
Type: Family

This entry includes 3-dehydroquinate synthase and 2-deoxy-scyllo-inosose synthase, both belonging to the 3-dehydroquinate synthase family. 2-deoxy-scyllo-inosose synthase catalyses the intramolecular carbocycle formation from D-glucose-6-phosphate to 2-deoxy-scyllo-inosose (DOI) . 3-dehydroquinate synthase catalyses the formation of dehydroquinate (DHQ) and orthophosphate from 3-deoxy-D-arabino heptulosonic 7 phosphate . This reaction is part of the shikimate pathway which is involved in the biosynthesis of aromatic amino acids.

This entry also matches 2-epi-valiolone synthase (EVS). Together with 2-epi-5-epi-valiolone synthases (EEVS) and desmethyl-4-deoxygadusol synthases (DDGS), EVS is part of the subgroup of sedoheptulose 7-phosphate cyclases found in DHQS-like proteins. EVS allows the synthesis of 2-epi-valiolone (2EV) from sedoheptulose 7-phosphate, predicted to be an alternative precursor of the aminocyclitol biosynthesis .
Putative peptide maturation dehydrogenase (SagB-rel_DH_2)
Type: Family

Members resemble the peptide maturation dehydrogenase SagB of thiazole and oxazole modification systems, and occur in a what appears to be a new type of peptide modification system. One adjacent marker is a new type of nitrile hydratase alpha subunit-related putative precursor,

, distantly related the NHLP leader peptide family

. Another is a large protein,

, with regions similar to adenylate cyclases and TPR proteins.
Putative peptide modification system cyclase (Mod_pep_cyc)
Type: Family

Members of this family show homology to mononucleotidyl cyclases and to tetratricopeptide repeat (TPR) proteins. Members occur next to two other markers of ribosomal peptide modification systems. One is a dehydrogenase related to SagB proteins from thiazole/oxazole modification systems. The other is the putative precursor, related to the nitrile hydratase-related leader peptide (NHLP) and nitrile hydratase alpha subunit families. These systems occur in many species of Xanthomonas and Stenotrophomonas, among others.
dTDP-4-dehydro-6-deoxyglucose aminotransferase (PLP_DesI)
Type: Family

Members of this family are pyridoxal phosphate-dependent aminotransferases that convert TDP-4-keto-6-deoxy-D-glucose to the 4-amino sugar form, TDP-4-amino-4,6-dideoxy-D-glucose. In Streptomyces venezuelae, this enzyme is designated DesI, catalyzing the third of six steps in the biosynthesis of TDP-D-desosamine, a component of a number of different macrolide antibiotics made by that organism. Related proteins, scoring below the trusted cutoff, include sugar aminotranferases in O-antigen biosynthesis regions .
RapG/RapK inhibitor (RapG/K_inhib)
Type: Family

Phr peptides are short peptides, best conserved in their amino-terminal regions, that are almost always encoded immediately downstream of a Rap phosphatase. A portion of the Phr peptide is secreted, enters another cell, and forms a quorum-sensing system by inhibiting its Rap phosphatase partner. The set of Phr peptides recognised by this entry is different from the PhrC/PhrF set recognised by

.
Tryptophan 2-C-methyltransferase (B12_rSAM_trp_MT)
Type: Family

Members of this family are the B12-binding domain/radical SAM domain enzyme tryptophan methyltransferase, named TsrT in the cassette for thiostrepton biosynthesis. Thiostrepton and related thiopeptides are synthesised by extensive modification of a ribosomally translated product, but this enzyme is involved in a pathway that converts a free Trp residue to a quinaldic acid moiety before it is appended .
Probable phospholipid ABC transporter-binding protein MlaD (ABC_MlaD)
Type: Family

Members of this protein family are the intermembrane phospholipid transport system binding protein MlaD (maintenance of Lipid Asymmetry D) of an ABC transport system that removes phospholipid from the outer leaflet of the Gram-negative bacterial outer membrane (OM), leaving only lipopolysaccharide in the outer leaflet. The Mla locus has long been associated with toluene tolerance, consistent with the proposed role in retrograde transport of phospholipid and therefore with maintaining the integrity of the OM as a protective barrier . MlaD forms extremely stable hexamers within the complex, functions in substrate binding with strong affinity for phospholipids, and modulates ATP hydrolytic activity .
Aminoglycoside N(6')-acetyltransferase, AacA4 type (N6_acetyl_AAC6)
Type: Family

Members of this family are the aacA4 type of aminoglycoside N(6')-acetyltransferase (

), an enzyme that modifies and inactivates aminoglycoside antibiotics such as kanamycin, neomycin, tobramycin, and amikacin. Members are regularly spread among pathogens into integron, transposon, and plasmid loci, with recombination often happening within the protein-coding region .
UrcA family protein (UrcA_uranyl)
Type: Family

Members of this family feature an N-terminal signal sequence, small size, and two invariant Cys residues, 10-20 residues apart. One member of this family, UrcA from the aerobic bacterium Caulobacter crescentus, is expressed so highly in response to uranium, but not other heavy metals, that a genetically engineered strain expressing green fluorescent protein in place of UrcA serves as a biodetector for micromolar uranyl ion. Caulobacter crescentus tolerates high levels of UVI exposure by mineralising the uranium. UrcA and its homologues may participate in such a process .
Conserved hypothetical protein CHP04434 (CHP04434)
Type: Family

The function of this family of proteins is unknown, but in all cases a PLP-dependent enzyme (a cysteine desulfurase homologue) is found nearby.
Restriction system-associated AAA family ATPase (Restrict_AAA)
Type: Family

Members of this family are AAA family ATPases by homology. They occur regularly in a conserved gene neighbourhood with the restriction (R), modification (M), and specificity (S) proteins of an apparent type I restriction enzyme system, plus one additional uncharacterised protein. It is not clear whether members of this family contribute to restriction per se, or to another process such as transfer of mobile elements.
Putative 2OG-Fe(II) oxygenase (SpoChoClust_3)
Type: Family

This family, related to streptomycin biosynthesis protein StrG and to phytanoyl-CoA dioxygenase, belongs to the 2-oxoglutarate and Fe(II)-dependent oxygenase clan, which includes not just dioxygenases such as phytanoyl-CoA dioxygenase PhyH, but also some chlorinating enzymes involved in natural product biosynthesis. Members of this family occur so far only in O-antigen biosynthesis regions of select Leptospira, and include an ~80 residue additional C-terminal region shared by no other proteins.
Putative modified peptide (Mod_pep_NH_fam)
Type: Family

Members of this family average 110 residues in length, with strong N-terminal homology to both the nitrile hydratase (NH) alpha subunit and thiazole/oxazole-modified microcin family (

) of NH-related ribosomally translated natural product precursors. A neighbouring gene resembles SagB, the dehydrogenase of many thiazole and oxazole modified peptide systems, supporting the hypothesis that members of this family are post-translationally modified.
7-carboxy-7-deazaguanine synthase, Cx14CxxC-type (QueE_Cx14CxxC)
Type: Family

In the pathway of 7-cyano-7-deazaquanine (preQ0) biosynthesis, the radical SAM enzyme QueE is quite variable. This entry represents a variant form in which the three-Cys motif that binds the signature 4Fe-4S cluster takes the form Cx14CxxC, as in Burkholderia multivorans ATCC 17616. The crystal structure is known .
Fluorinase (Fluorinase)
Type: Family

Members of this family are fluorinase (also known as adenosyl-fluoride synthase,

), an enzyme involved in the first committed step in the biosynthesis of at least two different organofluorine compounds, it catalyses the formation of a C-F bond by combining S-adenosyl-L-methionine (SAM) and fluoride to generate 5'-fluoro-5'-deoxyadenosine (5'-FDA) and L-methionine . Few organofluorine natural products are known. Related enzymes include chlorinases (

) that lack fluorinase activity, although a fluorinase may show chlorinase activity .
Fluorothreonine transaldolase (F_threo_transal)
Type: Family

This entry represents the homologues of fluorothreonine transaldolase. Fluorothreonine transaldolase is involved in biosynthesis of 4-fluorothreonine, one of the few known naturally occurring organofluorine compounds . It mediates a L-threonine/fluoroaceldehyde conversion to 4-fluoro-L-threonine/acetaldehyde crossover reaction. It can also convert chloroacetaldehyde into 4-chloro-L-threonine .
Phosphate ABC transporter substrate-binding protein (PtsS_plasma)
Type: Family

Members of this family are the substrate-binding protein of the phosphate ABC transporter as found in Mollicutes genera such as Mycoplasma, Mesoplasma, and Spiroplasma. The most similar sequences outside this family are PtsS in phosphate binding protein family (

), but sequence architecture differs considerably. Members of this family are never lipoproteins.
SDR family mycofactocin-dependent oxidoreductase (SDR_subfam_2)
Type: Family

Members of this protein subfamily are putative oxidoreductases belonging to the larger SDR family. All members occur in genomes that encode a cassette for the biosynthesis of mycofactocin, a proposed electron carrier of a novel redox pool. Characterised members of this family are described as NDMA-dependent, meaning that a blue aniline dye serving as an artificial electron acceptor is required for members of this family to cycle in vitro, since the bound NAD residue is not exchangeable. This family resembles mycofactocin-dependent oxidoreductases (

) most closely in the N-terminal region, consistent with the published hypothesis of NAD interaction with mycofactocin. See

.
Electron transfer flavoprotein, mycofactocin-associated (Mft_EtfB)
Type: Family

Members of this small protein family are putative electron transfer flavoproteins, related to FixA from E. coli and EtfB from Methylophilus methylotrophus but clearly forming a distinctive clade. All members occur in species with a mycofactocin system.
Bacterial microcompartment shell protein EutL (EutL)
Type: Family

A bacterial microcompartment is a protein-based metabolic organelle where several enzymes and metabolites are brought together. EutL is one of the shell proteins that form the ethanolamine utilization (Eut) microcompartment. Its structure has been revealed .
Bacterial microcompartment shell protein PduB (PduB)
Type: Family

A bacterial microcompartment is a protein-based metabolic organelle where several enzymes and metabolites are brought together. PduB is one of the shell proteins that form the propanediol-utilization (Pdu) microcompartment. The structure of PudB has been solved .
Putative peptide maturation system protein (PpiC-rel_mature)
Type: Family

Members of this protein family have a novel N-terminal sequence region. The C-terminal region of these proteins share homology with proteins in the PpiC-type peptidyl-prolyl cis-trans isomerase entry (

). However, proteins in this family are not included in the IPR000297 entry, suggesting an origin within a branch of the PpiC family but subsequent neofunctionalisation with a rapid change of sequence. The genome context for members always includes an ATP-grasp enzyme associated with peptide modification and a short polypeptide likely to be the modification target.
Abortive infection protein, AbiA family (AbiA)
Type: Family

Members of this protein family are about 650 amino acids in length, with an N-terminal region related to reverse transcriptases. The only characterised member is AbiA, with reported activity as an abortive infection protein for phage defense in Lactococcus lactis and (heterologously) in Streptococcus thermophilus .
Abortive infection protein, AbiV family (AbiV)
Type: Family

Bacterial abortive infection (Abi) systems contain phage resistance proteins that limit viral replication. Abi mechanisms differ greatly. This family includes AbiV from Lactococcus lactis. AbiV interacts directly with the protein SaV in phage p2 and blocks translation of phage proteins .