SII-SWORD/CoKE huggingface dataset:
FeS assembly SUF system protein SufT, putative (FeS_assembly_SufT_put)
Type: Family

The function of these proteins is unknown but they are almost always encoded in operons for the SUF system of iron-sulphur cluster biosynthesis. In a few species the SUF system is present elsewhere on the chromosome. This group shares this property of association with the SUF system with a related group,

. These groups of proteins both share a domain of unknown function which covers the whole protein in

but only the C-terminal portion of proteins in this entry, which have an additional unique uncharacterised N-terminal domain. As these proteins are encoded immediately downstream of the cysteine desulphurase gene sufS in many contexts, they have been deignated SufT. Homologous proteins not covered by this entry or

are found in operons associated with phenylacetic acid (or other ring-hydroxylating) degradation pathways.
Urea ABC transporter, substrate-binding protein UrtA-like (ABC_urea-bd_UrtA)
Type: Family

This entry consists of ABC transporter substrate-binding proteins associated with urea transport and metabolism. This family includes UrtA from Cyanobacteria, which is encoded in an operon typically found adjacent to urease genes. It was shown in that disruption leads to the loss of high-affinity urea transport activity . It also includes the periplasmic component (FmdD) of an active transport system for short-chain amides and urea (FmdDEF), found in Methylophilus methylotrophus . These proteins tend to have the twin-arginine signal for Sec-independent transport across the plasma membrane.
ABC transporter, urea, permease protein, UrtC (ABC_transptr_urea_perm_UrtC)
Type: Family

This entry consists of ABC transporter permease proteins associated with urea transport and metabolism. They are encoded in a conserved five-gene transport operon typically found adjacent to urease genes. It was shown in Cyanobacteria that disruption leads to the loss of high-affinity urea transport activity .
ABC transporter, urea permease protein UrtB, bacterial-type (ABC_UrtB_bac)
Type: Family

This entry consists of ABC transporter permease proteins associated with urea transport and metabolism. They are encoded in a conserved five-gene transport operon typically found adjacent to urease genes. It was shown in Cyanobacteria that disruption leads to the loss of high-affinity urea transport activity .
ABC transporter, urea, ATP-binding protein, UrtE (ABC_transptr_urea_ATP-bd_UrtE)
Type: Family

This entry consists of ABC transporter ATP-binding proteins associated with urea transport and metabolism. They are encoded in a conserved five-gene transport operon typically found adjacent to urease genes. It was shown in Cyanobacteria that disruption leads to the loss of high-affinity urea transport activity .
ABC transporter, urea, ATP-binding protein, UrtD (ABC_transptr_urea_ATP-bd_UrtD)
Type: Family

This entry consists of ABC transporter ATP-binding proteins associated with urea transport and metabolism. They are encoded in a conserved five-gene transport operon typically found adjacent to urease genes. It was shown in Cyanobacteria that disruption leads to the loss of high-affinity urea transport activity .
Hydroxyacylglutathione hydrolase (Hydroxyacylglutathione_Hdrlase)
Type: Family

This entry represents hydroxyacylglutathione hydrolase, a detoxification enzyme also known as glyoxalase II. It follows lactoylglutathione lyase, also known as glyoxalase I, and acts to remove the toxic metabolite methylglyoxal and related compounds. This protein belongs to the broader metallo-beta-lactamase family .
Choline ABC transporter, substrate-binding protein (ABC_choline_sub-bd)
Type: Family

Partial phylogenetic profiling suggests that the ABC transporter periplasmic binding proteins in this entry are involved in choline uptake for glycine betaine biosynthesis. Genomes often carry several paralogs, one encoded together with the permease and ATP-binding components, and another encoded next to a choline-sulphatase gene, suggesting that different members of this protein family interact with shared components and give some flexibility in substrate. Of the two proteins from Sinorhizobium meliloti 1021, one designated ChoX has been shown experimentally to bind choline (though not various related compounds such as betaine) and to be required for about 60 % of choline uptake . In A. tumefaciens, the ABC-type choline transporter is encoded by the chromosomally located choXWV operon (ChoX, binding protein; ChoW, permease; and ChoV, ATPase). The ChoXWV transporter functions as a high-affinity choline transporter .
ABC transporter, choline, permease protein (ABC_transptr_choline_permease)
Type: Family

Partial phylogenetic profiling suggests that the ABC transporter permease proteins in this entry are involved in choline uptake for glycine betaine biosynthesis.
Choline-sulfatase (Choline-sulfatase)
Type: Family

This entry consists of known and predicted choline-sulphatase enzymes involved in the synthesis of glycine betaine from choline . The symbiotic soil bacterium Rhizobium meliloti can synthesise glycine betaine from choline-O-sulphate and choline to protect itself from osmotic stress . Glycine betaine biosynthesis is not, however, crucial for nodulation and nitrogen fixation. This biosynthetic pathway is encoded by the betICBA locus, which comprises a regulatory gene, betI, and three structural genes, betC (choline sulphatase), betB (betaine aldehyde dehydrogenase), and betA (choline dehydrogenase). betICBA genes constitute a single operon, despite the existence of intergenic regions that contain mosaic elements between betI and betC, and between betB and betA . betC lies adjacent to an ATP-binding cassette transporter and a LysR type regulator, but well away from betBA, in this species .
Choline sulfate utilization transcriptional regulator (TF_choline_sulphate-util)
Type: Family

This entry consists of transcription factors from the wider LysR family whose genes are typically divergently transcribed from choline-sulphatase genes. Choline-sulphatase synthesises choline, a precursor to the osmoprotectant glycine-betaine, by the hydrolysis of choline sulphate.
DnaA regulatory inactivator Hda (Hda)
Type: Family

This entry represents the Hda (Homologous to DnaA) proteins, which are about half the length of DnaA and homologous over the entire length of Hda. In Escherichia coli, the initiation of DNA replication requires DnaA bound to ATP rather than ADP; Hda helps facilitate the conversion of DnaA-ATP to DnaA-ADP, thus inhibiting the inititation of DNA replication .
Frataxin (Frataxin)
Type: Family

Frataxin is a mitochondrial protein, mutation of which leads to the disease Friedreich's ataxia . Its orthologs are widely distributed in the bacteria, associated with the ISC system for iron-sulphur cluster assembly, and designated CyaY. Friedreich's ataxia is a progressive neurodegenerative disorder caused by loss of function mutations in the gene encoding frataxin (FRDA). Frataxin mRNA is predominantly expressed in tissues with a high metabolic rate (including liver, kidney, brown fat and heart). Mouse and yeast frataxin homologues contain a potential N-terminal mitochondrial targeting sequence, and human frataxin has been observed to co-localise with a mitochondrial protein. Furthermore, disruption of the yeast gene has been shown to result in mitochondrial dysfunction. Friedreich's ataxia is thus believed to be a mitochondrial disease caused by a mutation in the nuclear genome (specifically, expansion of an intronic GAA triplet repeat) .
Penicillin-binding protein 2 (Penicillin-binding_protein_2)
Type: Family

This entry represents penicillin-binding protein 2 (PBP-2, also known as peptidoglycan D,D-transpeptidase MrdA), a protein whose gene (designated either pbpA or mrdA) is generally found next to the gene for RodA, a protein required for the rod (bacillus) shape in many bacteria . PBP-2 acts as a transpeptidase for cell elongation, hence it is involved in formation of the rod shape.
Urea amidolyase associated protein 2 (UAAP2)
Type: Family

A number of bacteria utilise urea as a nitrogen source by the urea carboxylase/allophanate hydrolase pathway, which uses biotin and consumes ATP, rather than by means of the nickel-dependent enzyme urease . This entry represents urea amidolyase associated protein 2 (UAAP2), one of a pair of homologous, tandem uncharacterised genes found together with the urea carboxylase and allophanate hydrolase genes .
Urea amidolyase associated protein 1 (UAAP1)
Type: Family

A number of bacteria utilise urea as a nitrogen source by the urea carboxylase/allophanate hydrolase pathway, which uses biotin and consumes ATP, rather than by means of the nickel-dependent enzyme urease . This entry represents urea amidolyase associated protein 1 (UAAP1), one of a pair of homologous, tandem uncharacterised genes found together with the urea carboxylase and allophanate hydrolase genes .
ABC transporter, urea utilisation-associated, substrate-binding protein (ABC_transptr_urea-assoc_sub-bd)
Type: Family

This entry consists of ABC transporter substrate-binding proteins associated with the urea carboxylase/allophanate hydrolase pathway, an alternative to urease for urea degradation. These proteins are specific to bacteria with the urea degradation pathway and are encoded close to the urea carboxylase and allophanate hydrolase genes. The substrate for this transporter is therefore likely to be urea or a compound from which urea is easily derived.
Urea carboxylase-associated, permease (Urea_CO2ase-assoc_permease)
Type: Family

A number of bacteria obtain nitrogen from urea by means of a biotin-and ATP-dependent urea degradation system distinct from the urease enzyme. The two characterised proteins of this system are the enzymes urea carboxylase and allophanate hydrolase, but other, uncharacterised proteins are encoded nearby in multiple organisms. This entry includes predicted permeases of the amino acid permease family, likely to transport either urea or a compound from which urea is derived. It is found so far only Actinobacteria, whereas a number of other species with the urea carboxylase have an adjacent ABC transporter operon.
Aromatic prenyltransferase, NscD-like (ABBA_NscD-like)
Type: Family

This entry represents fungal enzymes involved in secondary metabolite production such as Prenyltransferase nscD, Tryptophan dimethylallyltransferase, ftmPT2, LtxC from lyngbyatoxin biosynthesis and related proteins . This family also includes some proteins from bacteria, such as TleC, which has being identified as a prenyltransferase involved in the synthesis of teleocidin B in Streptomyces .

Prenyltransferase NscD is part of the biosynthetic gene cluster responsible for the production of neosartoricin, a prenylated anthracenone compound with T-cell antiproliferative activity, suggesting a physiological role as an immunosuppressive agent . In this pathway, the non-reducing polyketide synthase NscA likely synthesises and cyclises the decaketide backbone , while the hydrolase NscB facilitates product release via hydrolysis, followed by spontaneous decarboxylation. NscD specifically catalyses the transfer of a dimethylallyl group to the aromatic C5 position of the intermediate. This is followed by a stereospecific hydroxylation at C2, catalysed by the FAD-dependent monooxygenase NscC. Notably, the gene cluster does not encode an O-acetyltransferase, suggesting that the final 2-O-acetylation step required for neosartoricin biosynthesis is likely carried out by an unidentified enzyme .

Tryptophan dimethylallyltransferase (

) catalyses the first step of ergot alkaloid biosynthesis. Ergot alkaloids, which are produced by endophyte fungi, can enhance plant host fitness, but also cause livestock toxicosis to host plants. O-glucose prenyltransferase PaPT is required for the biosynthesis of fusicoccins, potent activators of plasma membrane H+-ATPases in plants causing constriction canker . O-dimethylallyltransferase cpaD is required for the biosynthesis of the fungal neurotoxin cyclopiazonic acid, a nanomolar inhibitor of Ca2+-ATPase .
Tryptophan dimethylallyltransferase (Trp_dimethylallylTrfase)
Type: Family

This entry represents the enzyme tryptophan dimethylallyltransferase (

), which catalyses the first step of ergot alkaloid biosynthesis . Ergot alkaloids, which are produced by endophyte fungi, can enhance plant host fitness, but also cause livestock toxicosis to host plants. This enzyme is part of a larger group of aromatic prenyltransferases that may act on trp-containing cyclic dipeptides, or on tyrosine or other related substrates. Tryptophan dimethylallyltransferase and related enzymes typically are of fungal origin are involved in the biosynthesis of secondary metabolites such as ergot alkaloids .
Phosphonate ABC transporter, substrate-binding protein (Phosphnate-bd)
Type: Family

This entry represents a subset of the broader family of phosphate/phosphonate binding protein ABC transporter components. Many of the proteins in this entry can be associated with pathways for the metabolism of phosphonates, particularly the C-P lyase system based on their genomic context; this includes the characterised PhnD protein from Escherichia coli . Note that not all of these proteins are encoded within a phosphonate metabolism context, but can be assumed to bind phosphonate compounds even in the absence of such context.

Bacterial high affinity transport systems are involved in active transport of solutes across the cytoplasmic membrane. Most of the bacterial ABC (ATP-binding cassette) importers are composed of one or two transmembrane permease proteins, one or two nucleotide-binding proteins and a highly specific periplasmic solute-binding protein. In Gram-negative bacteria the solute-binding proteins are dissolved in the periplasm, while in archaea and Gram-positive bacteria, their solute-binding proteins are membrane-anchored lipoproteins .
D-xylonate dehydratase YjhG/YagF (Dehydratase_YjhG/YagF)
Type: Family

Proteins in this entry are homologous to dihydroxy-acid dehydratases and have been found so far in two Acidobacteria, two Planctomycetes, Bacillus clausii (strain KSM-K16), and (in two copies each) in strains K12-MG1655 and W3110 of Escherichia coli. E. coli K-12 family strains have two D-xylonic acid dehydratases, YjhG and YagF. They can convert D-xylonate into 2-keto-3-deoxy- D-xylonate (KDX) .They are key enzymes in the biosynthesis of 1,2,4-butanetriol and other chemicals .
Transcription regulator PadR, acidobacterial-type (Tscrpt_reg_PadR_acidobac-type)
Type: Family

Proteins in this entry are putative transcriptional regulators of the wider PadR family, and are found primarily in species of the acidobacteria. These proteins are regularly encoded in the vicinity of a putative transporter protei
Acidobacterial duplicated orphan permease (ADOP)
Type: Family

These proteins are found mostly in three species of Acidobacteria, namely Acidobacteria bacterium (strain Ellin345), Acidobacterium capsulatum ATCC 51196, and Solibacter usitatus (strain Ellin6076), where they form large paralogous families. Each protein contains two copies of a predicted ABC transporter permease doamain. However unlike other proteins containing this domain these proteins are essentially never encoded fused or adjacent to ABC transporter ATP-binding protein (

) genes. This entry is termed ADOP, for Acidobacterial Duplicated Orphan Permease, to reflect the restricted lineage, internal duplication, lack of associated ATP-binding cassette proteins, and permease homology. The function of these proteins is unknown.
Soil-associated protein DUF3738 (DUF3738)
Type: Family

Bacterial reference strains encoding members of this protein family are all isolated from soil. These include 39 members from Solibacter usitatus Ellin6076, 27 from Acidobacterium sp. MP5ACTX8 (both Acidobacteria), and four from Pedosphaera parvula Ellin514 (Verrucomicrobia). The family is well-diversified, with few pairs showing greater than 50 % pairwise identity. A few members are fused to Peptidase_M56 domains (see

), to Sigma70_r2 domains (see

), or have a duplication of this domain.
VWFA-related, acidobacterial-type (VWFA-rel_acidobac-type)
Type: Family

This entry represents bacterial proteins that include a region related to the von Willebrand factor type A (VWFA) domain. These proteins are mostly found in the acidobacteria, where they have undergone a large paralogous expansion.
Conserved hypothetical protein CHP03437, C-terminal, (CHP03437_C)
Type: Domain

This entry describes a domain found in a group of uncharacterised proteins from actinobacteria. It is often found at the C-terminal end. It's function is unknown.
Methyltransferase EgtD-like (MeTrfase_EgtD-like)
Type: Family

This entry includes bacterial methyltransferase EgtD , and fungal N-methyltransferases .

Histidine-specific methyltransferase EgtD catalyses the methylations of histidine to form N-alpha, N-alpha ,N-alpha-trimethyl-L-histidine (also known as hercynine) .

4-Dimethylallyltryptophan N-methyltransferase mediates the second step of biosynthesis of ergot alkaloid biosynthesis. It catalyzes the N-methylation of 4-dimethylallyl-L-tryptophan in the presence of S-adenosyl-L-methionine, resulting in the formation of 4-dimethylallyl-L-abrine .

N-methyltransferase dtpB from Aspergillus flavus, is a component required for the biosynthesis of the dimeric diketopiperazine alkaloid ditryptophenaline. Peptide synthase dtpA forms the phenylalanyl-tryptophanyl cyclic dipeptide product cyclophenylalanyltryptophenyl from L-tryptophan and L-phenylalanine; and dtpB methylates cyclophenylalanyltryptophenyl to form cyclo-N-methylphenylalanyltryptophenyl .
SAM-dependent methyltransferase, EasF-type, putative (SAM_MeTrfase_EasF-type_put)
Type: Domain

This entry represents an uncharacterised domain of about 300 amino acids with homology to S-adenosylmethionine-dependent methyltransferases. Proteins with this domain are exclusively fungal. A few, such as EasF from Neotyphodium lolii, are associated with the biosynthesis of ergot alkaloids, a class of fungal secondary metabolites. EasF may, in fact, be the AdoMet:dimethylallyltryptophan N-methyltransferase, the enzyme that follows tryptophan dimethylallyltransferase (DMATS) in ergot alkaloid biosynthesis . Several other proteins in this entry, including mug158 (meiotically up-regulated gene 158 protein) from Schizosaccharomyces pombe (Fission yeast), contain an additional uncharacterised domain (

).
Ergothioneine biosynthesis protein EgtB (EgtB)
Type: Family

Members of this family include EgtB, and enzyme of the ergothioneine biosynthesis, as found in numerous Actinobacteria . Characterised homologues to this family include a formylglycine-generating enzyme that serves as a maturase for an aerobic sulfatase (cf. the radical SAM enzymes that serve as anaerobic sulfatase maturases).
Urea transporter, bacteria (Urea_transporter_bac)
Type: Family

Proteins in this family are bacterial urea transporters, found in species that contain urease, encoded adjacent to the urease operon. YUT (Yersinia urea transporter) proteins from the Gram-negative bacterium Yersinia peseudotuberculosis are also included in this family. Putative Yut urea channel exists only in the open state, allowing urea to enter into the cytoplasm down its concentration gradient .
Ergothioneine biosynthesis protein EgtC (EgtC)
Type: Family

Members of this strictly bacterial protein family show similarity to class II glutamine amidotransferases. They are distinguished by appearing in a genome context with, and usually adjacent to or between, members of families

(methyltransferase EgtD-like) and

(ergothioneine biosynthesis protein EgtB) .
Glutamate--cysteine ligase EgtA, Actinobacteria (EgtA_Actinobacteria)
Type: Family

Members of this bacterial protein family, EgtA, resemble the glutamate--cysteine ligase of the two-step pathway for glutathione (GSH) biosynthesis, but instead are involved in the biosynthesis of the histidine-derived thiol, ergothioneine (EGT). Successful in vitro reconstitution of EGT biosynthesis using EgtBCDE and gamma-L-glutamyl-L-cysteine suggests that this enzyme is a bone fide glutamate--cysteine ligase .
Mycothiol biosynthesis protein, MshB (Mycothiol_biosynthesis_MshB)
Type: Family

This entry represents the mycothiol biosynthesis protein MshB found in Mycobacterium tuberculosisand related species. This protein has been characterised as a 1D-myo-inosityl-2-acetamido-2-deoxy-alpha-D-glucopyranoside deacetylase .
Mycothiol S-conjugate amidase Mca (Mca)
Type: Family

Mycobacterium tuberculosis, Corynebacterium glutamicum (Brevibacterium flavum), and related species use the thiol mycothiol in place of glutathione. This enzyme, homologous to the (dispensable) MshB enzyme of mycothiol biosynthesis, is described as an amidase that acts on conjugates to mycothiol , and functions as a detoxification enzyme.
Mycothiol ligase MshC (Mycothiol_ligase_MshC)
Type: Family

This entry represents MshC, a l-cysteine:1-D-myo-inosityl 2-amino-2-deoxy-alpha-D-glucopyranoside ligase enzyme that uses ATP to ligate a Cys residue to a mycothiol precursor molecule, in the second to last step in mycothiol biosynthesis . This enzyme shows considerable homology to Cys--tRNA ligases, and many proteins are wrongly annotated as such. Mycothiol is found in Mycobacterium tuberculosis , Corynebacterium glutamicum (Brevibacterium flavum), Streptomyces coelicolor, and various other members of the Actinobacteria. Mycothiol is an analog of glutathione.
Mycothiol acetyltransferase (Mycothiol_AcTrfase)
Type: Family

Low-molecular weight thiols play an essential role in the metabolism of organsism as coenzymes and cofactors that facilitate important biochemical processes in conjunction with proteins. The predominant low-molecular weight thiol in the actinomycetes is mycothiol, which is involved in the maintenance of cellualar redox state, detoxification of electrophiles and resistance to antimicrobials . The pathway of mycothiol biosynthesis is therefore a potential target for the development of new drugs to treat pathogenic actinomycetes such as Mycobacterium tuberculosis.

This entry represents the MshD protein catalysing the final step of mycothiol biosynthesis, the acetylation of the cysteinyl amine in cysteine-glucosamine-inositol (Cys-GlcN-Ins) . MshD is a monomeric enzyme consisting of two tandemly-repeated domains which each adopt the GCN5-related N-acetyltransferase (GNAT) fold .
Mycothiol biosynthesis protein, MshA (Mycothiol_biosynthesis_MshA)
Type: Family

Members of this protein family, found exclusively in the Actinobacteria, are MshA, the glycosyltransferase of mycothiol biosynthesis . Mycothiol replaces glutathione in these species.
Myo-inositol 1-phosphate synthase, actinobacteria (Myo-inos-1-P_Synthase_actino)
Type: Family

This entry represents Inositol-3-phosphate synthase 1 (INO1), also known as Myo-inositol 1-phosphate synthase, and similar sequences found in actinobacteria. INO1 is a key enzyme in myo-inositol biosynthesis pathway that catalyses the conversion of glucose 6-phosphate to 1D-myo-inositol 3-phosphate in a NAD-dependent manner .
S-(hydroxymethyl)mycothiol dehydrogenase (MycoS_dep_FDH)
Type: Family

Members of this family are mycothiol-dependent formaldehyde dehydrogenase enzymes (

) . This protein is found, so far, only in the Actinobacteria (Mycobacterium species, Streptomyces species, Corynebacterium species and related species), where mycothione replaces glutathione.
Mycothione reductase (Mycothione_reductase)
Type: Family

Mycothiol, a glutathione analog in Mycobacterium tuberculosis and related species, can form a disulphide-linked dimer called mycothione. This enzyme can reduce mycothione to regenerate two mycothiol molecules. The enzyme shows some sequence similarity to glutathione-disulphide reductase, trypanothione-disulphide reductase, and dihydrolipoamide dehydrogenase. The characterised protein from M. tuberculosis, a homodimer, has one FAD cofactor per monomer, and uses NADPH as a substrate .