SII-SWORD/CoKE huggingface dataset:
Bacterial OB-fold (BOF)
Type: Domain

Proteins in this entry have an OB-fold fold (oligonucleotide/oligosaccharide binding motif). Analysis of the predicted nucleotide-binding site of the OB-fold suggests that they lack nucleic acid-binding properties. They contain a predicted N-terminal signal peptide which indicates that they localise to the periplasm where they may function to bind proteins, small molecules, or other typical OB-fold ligands. As hypothesised for the distantly related OB-fold containing bacterial enterotoxins, the loss of nucleotide-binding function and the rapid evolution of the OB-fold ligand-binding site may be associated with the presence of members in mobile genetic elements and their potential role in bacterial pathogenicity .
Competence protein ComF (Competence_ComF)
Type: Family

Competence is the ability of a cell to take up exogenous DNA from its environment, resulting in transformation. It is widespread among bacteria and is probably an important mechanism for the horizontal transfer of genes. DNA usually becomes available by the death and lysis of other cells. Competent bacteria use components of extracellular filaments called type 4 pili to create pores in their membranes and pull DNA through the pores into the cytoplasm. This process, including the development of competence and the expression of the uptake machinery, is regulated in response to cell-cell signalling and/or nutritional conditions .

The development of genetic competence in Bacillus subtilis is a highly regulated adaptive response to stationary-phase stress. For competence to develop, the transcriptional regulator, ComK, must be activated. ComK is required for the expression of genes encoding proteins that function in DNA uptake. In log-phase cultures, ComK is inactive in a complex with MecA and ClpC. The comS gene is induced in response to high culture cell density and nutritional stress and its product functions to release active ComK from the complex. ComK then stimulates the transcription initiation of its own gene as well as that of the late competence operons .

Proteins in this family are found in bacterial species which posses systems for natural transformation (competence) (eg Bacillus subtilis, Haemophilus influenzae), and also species without these systems (eg Escherichia coli). Competence protein F has been shown to be important for the uptake of exogenous DNA in naturally competent bacteria, though the precise role of this protein is not yet known . GntX is a periplasmic gluconate binding protein thought to be part of a high-affinity gluconate transport system .
Sugar fermentation stimulation protein (SfsA)
Type: Family

This family contains sugar fermentation stimulation protein SfsA, which is probably a regulatory factor involved in maltose metabolism. SfsA has been shown to bind DNA and described as a nuclease, as it contains a well-conserved PDDEXK nuclease active site. The structure of SfsA has been solved (

,

)
Small GTP-binding domain (Small_GTP-bd)
Type: Domain

Proteins with a small GTP-binding domain include Ras, RhoA, Rab11, translation elongation factor G, translation initiation factor IF-2, tetratcycline resistance protein TetM, CDC42, Era, ADP-ribosylation factors , tdhF, and many others . In some proteins the domain occurs more than once. Among them there is a large number of small GTP-binding proteins and related domains in larger proteins. Note that the alpha chains of heterotrimeric G proteins are larger proteins in which the NKXD motif is separated from the GxxxxGK[ST] motif (P-loop) by a long insert and are not easily detected by this model.
UPF0014 family (UPF0014_fam)
Type: Family

Characterised proteins in this family include probable iron export permease protein FetB, which is part of the ABC transporter complex FetAB, probably involved in iron export , and aluminum sensitive 3 protein, also part of an ABC transporter required for aluminum (Al) resistance . This family also includes integral membrane proteins currently uncharacterised.
Putative pre-16S rRNA nuclease (YqgF)
Type: Family

This entry represents a group of predicted nucleases involved in processing of the 5'-end of pre-16S rRNA. This entry typified by the Escherichia coli protein YqgF, which exhibits an RNAse H fold in crystal structure and is involved in the processing of pre-16S rRNA during ribosome maturation .
Endoribonuclease YicC/YloC-like (YicC/YloC-like)
Type: Family

This entry represents Endoribonucleases YicC from Escherichia coli and YloC from Bacillus subtilis, and similar bacterial sequences. YicC has been shown to be important for cells in the stationary phase, and essential for growth at high temperatures . This protein contributes to degradation of the iron-responsive small RNA (sRNA) RhyB via collaboration with the exoribonuclease PNPase . It seems to generate a 3'-OH and a 5'-phosphate group. It cleaves preferentially at U residues, but has no activity on dsRNA or dsDNA . Similarly , YloC was shown to be a metal-dependent enzyme that catalyses the cleavage of single-stranded RNA, preferentially at U residues, and exists in an oligomeric form, most likely a hexamer. As such, YloC shares some characteristics with the SARS-CoV Nsp15 endoribonuclease .
TraB, bacterial/archaeal (TraB_bac)
Type: Family

In prokaryotes, for example Enterococcus faecalis (Streptococcus faecalis), the conjugative transfer of certain plasmids is controlled by peptide pheromones . Plasmid free recipient cells secret plasmid specific oligopeptides, termed sex pheromones. They induce bacterial clumping and specifically activate the conjugative transfer of the corresponding plasmid. Once recipient cells acquire the plasmid they start to produce a pheromone inhibitor to block the activity of the pheromone and to prevent plasmid containing cells from clumping; they also become donor cells able to transfer the plasmid to plasmid free recipient cells. Examples of such plasmid-pheromone systems are bacteriocin plasmid pPD1 , haemolysin/bacteriocin plasmid, pAD1 , tetracycline-resistance plasmid, pCF10 , and the haemolysin/bacteriocin plasmid, pOB1 .

TraB in combination with another factor contributes to pheromone shutdown in cells that have acquired a plasmid. Based on its homology with TIKI proteins, TraB may act as a protease to inactivate the mating pheromone .
Nascent polypeptide-associated complex (NAC), archaeal (NAC_arc)
Type: Family

Eukaryotic NAC, an abundant heterodimer composed of two homologous subunits, reversibly binds eukaryotic ribosomes and is located in direct proximity to nascent polypeptides as they emerge from the ribosome . Despite being implicated in diverse cellular functions, its role
in vivo
is still not completely understood. It is thought that NAC may function as a shield protecting the nascent chain from inappropriate interactions with cytosolic factors, and could regulate further translation of the polypeptide through its interaction with the ribosome.

Archaeal NAC is a homodimer which appears to be functionally analogous to the eukaryotic form, associating with ribosomes and contacting the nascent polypeptide chain emerging on the ribosome . It has two domains; the NAC domain, which it shares with eukaryotic NAC, and a C-terminal UBA domain also found on the alpha, but not beta, subunit of eukaryotic NAC. The NAC domain forms a six-stranded β-barrel structure which shows some similarities to the OB fold. This domain appears to be responsible for dimerisation, nucleic acid binding, and nascent polypeptide binding. The UBA domain is typical of ubiquitin or polyubquitin-binding proteins; its physiological role is unclear but it was suggested that it may compete with the proteosome for ubiquitin, thus inhibiting ubiquitin-mediated protein degradation.
Pyridinium-3,5-bisthiocarboxylic acid mononucleotide synthase LarE (LarE)
Type: Family

This family includes LarE, one of three accessory proteins (the others being LarB and LarC) present in the lactate racemization operon larA-E. LarA is a nickel-dependent lactate racemase, and the accessory proteins are required for the incorporation of Ni in the lactate racemase apoprotein . The accessory proteins LarB, LarC, and LarE are widely distributed in microorganisms. Among them, LarC and LarE have been found to be Ni-containing proteins .
Chromosome segregation/condensation protein ScpB (ScpB_csome_segregation)
Type: Family

This family represents ScpB, which along with ScpA (

) interacts with SMC in vivo forming a complex that is required for chromosome condensation and segregation . The SMC-Scp complex appears to be similar to the MukB-MukE-Muk-F complex in Escherichia coli , where MukB (

) is the homologue of SMC. ScpA and ScpB have little sequence similarity to MukE (

) or MukF (

), they are predicted to be structurally similar, being predominantly α-helical with coiled coil regions.
Metallophosphoesterase, YmdB-like (YmdB-like)
Type: Family

This family of putative phosphoesterases contains the characterised B. subtilis protein 2',3'-cyclic-nucleotide 2'-phosphodiesterase (previously known as YmdB). 2',3'-cyclic-nucleotide 2'-phosphodiesterase has been shown to be essential for biofilm formation and to be a global regulator of late adaptive responses .

Another member of this family from Deinococcus radiodurans has been crystallized and is described as a novel phosphatase/phosphodiesterase .
Dihydropteroate synthase-related protein synthase-related protein (Dihydropt_synth)
Type: Family

The proteins of this family have been found so far only in the four archaeal species. The central region of the proteins shows considerable homology to the amino-terminal half of dihydropteroate synthases.
Uncharacterised protein MJ0570 (MJ0570)
Type: Family

This family of conserved hypothetical proteins has no known function. Homologous proteins related to MJ0570 of Methanocaldococcus jannaschii (Methanococcus jannaschii) include both the apparent orthologs in the family, the much longer protein YLR143W from Saccharomyces cerevisiae (Baker's yeast), and second homologous proteins from Archaeoglobus fulgidus and Pyrococcus horikoshii that appear to represent a second orthologous group.
ComB-like (ComB-like)
Type: Family

2-phosphosulpholactate phosphatase (ComB;

) is a magnesium-dependent acid phosphatase that catalyzes the second step in coenzyme M (CoM; 2-mercaptoethanesulphonic acid) biosynthesis, namely, the hydrolysis of (2R)-2-phospho-3-sulpholactate to yield (2R)-3-sulpholactate and phosphate. CoM is an essential cofactor that acts as the terminal methyl carrier in methanogenesis . CoM has also a role in the bacterial pathway of aliphatic epoxide carboxylation . Homologues of ComB have been identified in all available cyanobacterial genome sequences and in genomes from phylogenetically diverse bacteria and archaea. However, many of these organisms lack homologues of other CoM biosynthetic genes.

ComB has a complex α/β topology. The monomer is composed of two domains thought to be related by a common ancestral gene, plus a C-terminal helical and β-hairpin region .
Bifunctional arginine dihydrolase/ornithine cyclodeaminase ArgZ/ArgE-like (ArgZ/ArgE-like)
Type: Family

This entry includes the bifunctional arginine dihydrolase/ornithine cyclodeaminase ArgZ (also known as as Sll1336), ArgE from Synechocystis sp and similar prokaryotic sequences. ArgZ is involved in an ornithine-ammonia cycle (OAC) in cyanobacteria, which confers substantial adaptability under environmental nitrogen fluctuations. This protein is organised into three domains: a N-terminal domain belonging to the guanidino group-modifying enzyme (GME) family, a middle oxoglutarate reductase/saccharopine dehydrogenase bifunctional enzyme (

) and a C-terminal region that can be divided in two subdomains (

and

) .
Protein of unknown function DUF389 (DUF389)
Type: Family

This family of conserved hypothetical proteins has no known function. It includes potential integral membrane proteins.
Thioredoxin-like, prokaryotic (THIRX-like_proc)
Type: Family

This entry represents a group of related prokaryotic sequences, including Thioredoxin from Methanothermobacter thermautotrophicus. This protein has been reported to not function as a glutathione-disulfide oxidoreductase in the presence of glutathione and glutathione reductase and show low thioredoxin activity in vitro . ArsE from Shewanella putrefaciens (

) is also included in this group. It is a small, thioredoxin-like component of a nitroreductase active in converting the nitro group of two different synthetic aromatic organoarsenical compounds to an amine .
Conserved hypothetical protein CHP00454 (CHP00454)
Type: Family

This entry describes a family of conserved hypothetical proteins with no known function.
O-phosphoseryl-tRNA(Cys) ligase (O-Pseryl-tRNA(Cys)_ligase)
Type: Family

This entry represents archaeal phenylalanyl-tRNA ligase alpha chains. It was shown to act in a proposed pathway of tRNA(Cys) indirect aminoacylation, resulting in Cys biosynthesis from O-phosphoserine, in certain archaea. It charges tRNA(Cys) with O-phosphoserine. The pscS gene product converts the phosphoserine to Cys .
YbhB/YbcL/LppC-like (YbhB_YbcL/LppC-like)
Type: Family

This family contains Escherichia coli YbhB and YbcL, two bacterial homologues to Raf kinase inhibitor proteins from mammals (RKIP, previously known as PEBP), according to structural similarity. YbhB and YbcL have specific features, for example a substrate binding pocket formed by the dimerization interface and the absence of cis peptide bonds which could correspond to the recognition of multiple cellular partners . YbcL encoded by Uropathogenic Escherichia coli (UPEC) acts on the uroepithelium and attenuates neutrophil migration during infection .

This family also includs LppC from M. tuberculosis, which is likely involved in bacterial recognition and uptake by its host .
Nicotinate/nicotinamide nucleotide adenylyltransferase (NadD/NMNAT)
Type: Family

This family contains the adenylyltransferases for nicotinamide-nucleotide and for the deamido form, nicotinate nucleotide found predominantly in bacteria and fungi. Nicotinamide-nucleotide adenylyltransferase (NMNAT,

) synthesizes NAD by the salvage pathway, while nicotinate-nucleotide adenylyltransferase (NaMN-ATase,

) synthesizes the immediate precursor of NAD by the de novo pathway.
Ap4A hydrolase (YqeK)
Type: Family

This entry represents Bis(5'-nucleosyl)-tetraphosphatase, symmetrical from Staphylococcus aureus (YqeK, also known as Ap4A hydrolase) and similar bacterial proteins. YqeK functions as a hydrolase of diadenosine tetraphosphate (Ap4A), cleaving symmetrically to yield two molecules of ADP .
Ribose-1,5-bisphosphate isomerase (R15Pi)
Type: Family

The delineation of this family was based originally, in part, on a discussion and neighbour-joining phylogenetic study of archaeal and other proteins homologous to the alpha, beta, and delta subunits of eukaryotic initiation factor 2B (eIF-2B), a five-subunit molecule that catalyses GTP recycling for eIF-2 .

Later, this group of archaeal proteins have been shown to function as ribulose-1,5 bisphosphate isomerases (R15Pi). Thermococcus kodakarensis R15Pi, also known as TK0185, converts d-ribose 1,5-bisphosphate into ribulose 1,5-bisphosphate, providing the substrate for archaeal ribulose-1,5-bisphosphate carboxylase/oxygenases. Its structure has been revealed .
Methylthioribose-1-phosphate isomerase (IF-M1Pi)
Type: Family

This family contains proteins designated as 5-methylthioribose-1-phosphate isomerase (MTNA,

, ). It also contains putative translation initiation factor 2B subunit proteins.

5-methylthioribose-1-phosphate isomerase (MTNA) participates in the methionine salvage pathway catalysing the isomerisation of 5-methylthioribose-1-phosphate to 5-methylthio ribulose-1-phosphate . The methionine salvage pathway leads to the synthesis of methionine from methylthioadenosine, the end product of the spermidine and spermine anabolism in many species.

The delineation of this family is based in part on a discussion and neighbour-joining phylogenetic study , of archaeal and other proteins homologous to the alpha, beta, and delta subunits of eukaryotic initiation factor 2B (eIF-2B), a five-subunit molecule that catalyzes GTP recycling for eIF-2. The archaeal proteins are related to the common ancestor of eIF-2B alpha, beta, and delta rather then specifically to any one of them, and that designation of particular archaeal members as corresponding to eIF-2B alpha or eIF-2B delta is imprecise. It has been suggested that designating the archaeal proteins as translation initiation factors remains unproven.
Coenzyme A biosynthesis bifunctional protein CoaBC (CoaBC)
Type: Family

This entry represents a bifunctional enzyme CoaBC (gene name dfp) that catalyses the second and third steps (cysteine ligation, (

), and decarboxylation, (

)) in the biosynthesis of coenzyme A (CoA) from pantothenate in bacteria. This enzyme contains the FMN cofactor, but no FAD or pyruvoyl group. The amino-terminal region is responsible for the phosphopantothenoylcysteine decarboxylase activity .

The protein product of the dfp gene in Escherichia coli was found to be able to restore a temperature-sensitive conditionally lethal mutation that resulted in a slow cessation of DNA synthesis . The protein encoded by dfp was then found to affect both DNA and pantothenate metabolism . Later, phosphopantothenate-cysteine ligase activity, which is involved in the biosynthesis of coenzyme A, was demonstrated in the same protein. Therefore this protein has been named bifunctional protein CoaBC .
Conserved hypothetical protein CHP00529 (CHP00529)
Type: Family

This protein is predicted to have 10 transmembrane regions. Members of this family are found so far in the Archaea (Archaeoglobus fulgidus and Pyrococcus horikoshii) and in a bacterial thermophile, Thermotoga maritima. In Pyrococcus, the gene is located between nadA and nadB, two components of an enzyme involved in de novo synthesis of NAD. By PSI-BLAST, this family shows similarity (but not necessarily homology) to gluconate permease and other transport proteins.
Heme biosynthesis-associated TPR protein (Heme_biosyn_assoc_TPR_pro)
Type: Family

This is a family of uncharacterised tetratricopeptide repeat (TPR) proteins invariably found in heme biosynthesis gene clusters. The absence of any invariant residues other than Ala argues against this protein serving as an enzyme per se. The gene symbol hemY assigned in E. coli is unfortunate in that an unrelated protein, protoporphyrinogen oxidase (HemG in E. coli) is designated HemY in Bacillus subtilis.
PdxA family (PdxA_fam)
Type: Family

This entry represents the PdxA family. PdxA is an NAD+-dependent 4-hydroxythreonine 4-phosphate dehydrogenase (

) active in pyridoxal phosphate biosynthesis . PdxA2, a functional paralogue of PdxA, catalyzes the NAD-dependent oxidation and subsequent decarboxylation of D-erythronate 4-phosphate to produce dihydroxyacetone phosphate (DHAP). It can also use D-threonate 4-phosphate as substrate . This family also includes TphB, involved in terephthalate degradation .
Anthranilate synthase component I, PabB-like (Anth_synth_I_PabB)
Type: Family

This enzyme resembles some other chorismate-binding enzymes, including para-aminobenzoate synthase (pabB) and isochorismate synthase. There is a fairly deep split between two sets, seen in the pattern of gaps as well as in amino acid sequence differences. This group includes eukaryotes, archaea, and many bacterial lineages; sequences from the second group may resemble pabB more closely than other trpE from the other group. The other group includes Gram-negative proteobacteria such as Escherichia coli and Helicobacter pylori but also the Gram-positive organism Corynebacterium glutamicum, and is described by

.
Anthranilate synthase component I, TrpE-like, bacterial (Anth_synth_I_TrpE)
Type: Family

This family represents anthranilate/para-aminobenzoate synthase component I from proteobacteria and actinobacteria.
Primosomal protein N' (PriA)
Type: Family

This entry represents primosomal protein N' (PriA) proteins found mainly in prokaryotic organisms. It also describes PriA-related proteins found in invertebrate organisms and some fungi.

Primosomal protein N', also known as ATP-dependent helicase PriA, is a component of the primosome, which is involved in replication, repair, and recombination. PriA serves as a sensor/stabiliser for an arrested replication fork, which is lethal in bacteria if left unrepaired and eventually promotes restart of DNA replication through the assembly of a primosome. It also serves as a checkpoint protein that prevents the replicase from advancing in a strand displacement reaction on forks that do not contain a functional replicative helicase . This protein shows a modular arrangement in which its central helicase core is surrounded by several DNA-binding elements, including a 3'DNA-binding domain

at the N-terminal. This domain is usually followed by a circularly permuted winged helix (WH) domain

. At the C-terminal, there is a Cys-rich region (CRR) domain

, which is embedded within the C-terminal helicase lobe

, followed by the C-terminal domain (CTD)

.
Aspartate kinase, monofunctional class (Asp_kin_monofn)
Type: Family

This entry describes a subclass of the aspartate kinases that are mostly Lys-sensitive and are not fused to homoserine dehydrogenase. The E. coli enzyme is a homodimer, while the Bacillus and Corynebacterium enzymes are alpha 2/beta 2 heterotetramers, where the beta subunit is translated from an in-phase alternative initiator at Met-246 . The protein slr0657 from Synechocystis PCC6803 is extended by a duplication of the C-terminal region corresponding to the beta chain. Incorporation of a second copy of the C-terminal domain may be quite common in this subgroup of aspartokinases.

Aspartate kinase catalyses the first step in the biosynthesis of Lys (via its precursor diaminopimelate), Met, and Thr. In Escherichia coli, a distinct isozyme is inhibited by each of these three amino acid end products . The Met-sensitive (I) and Thr-sensitive (II) forms are bifunctional enzymes fused to homoserine dehydrogenase, which catalyses the next step in the biosynthesis of these amino acids. In contrast, the Lys-sensitive form (III) is a monofunctional enzyme; homoserine dehydrogenase is not part of the Lys biosynthetic pathway.
Inner membrane protein YohK-like (YohK-like)
Type: Family

Members of this small but broadly distibuted (Gram-positive, Gram-negative, and Archaeal) family appear to have multiple transmembrane segments. The function is unknown.
MJ1255-like (MJ1255-like)
Type: Domain

The function of this domain is unknown. A small region (~50 amino acids) within the domain appears to be related to a family of sugar transferases.
4-hydroxy-tetrahydrodipicolinate synthase, DapA (DapA)
Type: Family

4-hydroxy-tetrahydrodipicolinate synthase dapA is a homotetrameric enzyme of lysine biosynthesis. It catalyses the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA) . E. coli has several paralogs closely related to dihydrodipicoline synthase, as well as the more distant N-acetylneuraminate lyase.
N-acetylneuraminate lyase (NanA)
Type: Family

N-acetylneuraminate lyase (or N-Acetylneuraminic acid aldolase, NAL) catalyzes the cleavage of N-acetylneuraminic acid (sialic acid) to form pyruvate and N-acetyl-D-mannosamine. The enzyme plays an important role in the regulation of sialic acid metabolism in bacteria. It has a widespread application as biocatalyst for the synthesis of sialic acid and its derivatives . This enzyme has been shown to be quite specific for pyruvate as the donor, but flexible to a variety of D-and, to some extent, L-hexoses and pentoses as acceptor substrates. NAL is member of dihydrodipicolinate synthase family that comprises several pyruvate-dependent class I aldolases .
Protoporphyrinogen oxidase HemJ-like (HemJ-like)
Type: Family

This entry includes HemJ (

) from Synechocystis sp. (strain PCC 6803 / Kazusa). It is essential for protoporphyrinogen IX oxidase activity and is functionally coupled with coproporphyrinogen III oxidase .