SII-SWORD/CoKE huggingface dataset:
Acetate-CoA ligase (Ac_CoA_lig)
Type: Family

Acetyl-CoA synthetase (also known as acetate-CoA ligase and acetyl-activating enzyme) is a ubiquitous enzyme, found in both prokaryotes and eukaryotes, which catalyses the formation of acetyl-CoA from acetate, coenzyme A (CoA) and ATP as shown below :
ATP + acetate + CoA = AMP + diphosphate + acetyl-CoA
The activity of this enzyme is crucial for maintaining the required levels of acetyl-CoA, a key intermediate in many important biosynthetic and catabolic processes. It is especially important in eukayotic species as it is the only route for the activation of acetate to acetyl-CoA in these organisms (some prokaryotic species can also activate acetate by either acetate kinase/phosphotransacetylase or by ADP-forming acetyl-CoA synthase). Eukaryotes typically have two isoforms of acetyl-CoA synthase, a cytosolic form involved in biosynthetic processes and a mitochondrial form primarily involved in energy generation.

The crystal structures of a eukaryotic (

, from yeast) and bacterial (

, from Salmonella) form of this enzyme have been determined . The yeast enzyme is trimeric, while the bacterial enzyme is monomeric. The trimeric state of the yeast protein may be unique to this organism however, as the residues involved in the trimer interface are poorly conserved in other sequences. Despite differences in the oligomeric state of the two enzyme, the structures of the monomers are almost identical. A large N-terminal domain (~500 residues) containing two parallel β sheets is followed by a small (~110 residues) C-terminal domain containing a three-stranded β sheet with helices. The active site occurs at the domain interface, with its contents determining the orientation of the C-terminal domain.
Glutaredoxin-like, plant II (GlrX-like_pln_2)
Type: Family

Glutaredoxins , also known as thioltransferases (disulphide reductases), are small proteins of approximately one hundred amino-acid residues which utilise glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system .

Glutaredoxin functions as an electron carrier in the glutathione-dependent synthesis of deoxyribonucleotides by the enzyme ribonucleotide reductase. Like thioredoxin (TRX), which functions in a similar way, glutaredoxin possesses an active centre disulphide bond . It exists in either a reduced or an oxidized form where the two cysteine residues are linked in an intramolecular disulphide bond. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH ->GSH reductase ->GSH ->GRX ->protein substrates . By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress.

Glutaredoxin has been sequenced in a variety of species. On the basis of extensive sequence similarity, it has been proposed that Vaccinia virus protein O2L is most probably a glutaredoxin. Finally, it must be noted that Bacteriophage T4 thioredoxin seems also to be evolutionary related. In position 5 of the pattern T4 thioredoxin has Val instead of Pro.

This group of glutaredoxin-like proteins is apparently limited to plants. Multiple isoforms are found in Arabidopsis thaliana (Mouse-ear cress) and Oryza sativa(Rice).
Glutaredoxin domain (Glutaredoxin_dom)
Type: Domain

Glutaredoxins , also known as thioltransferases (disulphide reductases), are small proteins of approximately one hundred amino-acid residues which utilise glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system .

Glutaredoxin functions as an electron carrier in the glutathione-dependent synthesis of deoxyribonucleotides by the enzyme ribonucleotide reductase. Like thioredoxin (TRX), which functions in a similar way, glutaredoxin possesses an active centre disulphide bond . It exists in either a reduced or an oxidized form where the two cysteine residues are linked in an intramolecular disulphide bond. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH ->GSH reductase ->GSH ->GRX ->protein substrates . By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress.

Glutaredoxin has been sequenced in a variety of species. On the basis of extensive sequence similarity, it has been proposed that Vaccinia virus protein O2L is most probably a glutaredoxin. Finally, it must be noted that Bacteriophage T4 thioredoxin seems also to be evolutionary related. In position 5 of the pattern T4 thioredoxin has Val instead of Pro.

This C-terminal domain with homology to glutaredoxin is fused to an N-terminal peroxiredoxin-like domain.
Ribonuclease III (RNase_III)
Type: Family

This family consists of ribonuclease III (RNase III). This ubiquitous enzyme specifically cleaves double-stranded rRNA and is found in all bacteria and eukaryotes . In bacteria its main role is the processing of pre-rRNAs, where the large precursor ribosomal RNA molecules are cleaved at specific sites to produce the immediate precursors of the functional molecules. RNase III also functions in the maturation and degradation of mRNAs, and the maturation of tRNAs. In some organisms (eg. Escherichia coli) cells are viable without this enzyme, though they are impeded in growth, but in others (e.g. B. subtilis and M. genitalium) this enzyme is essential.

The bacterial RNase III enzymes so far characterised are homodimers with a molecular mass of ~50kDa . The endonuclease domain is located within the N-terminal two-thirds of the protein, containing several α-helices, but no β-strands. The double-stranded RNA binding domain is found at the C-terminal third of the protein, forming the α-β(3)-α fold common to dsRNA-binding proteins. A signature box of 11 conserved amino acids found in the N-terminal region of RNase III may contain the active site, though this has not been proven.
Lipopolysaccharide heptosyltransferase I (LipoPS_heptosylTferase-I)
Type: Family

This family consists of examples of ADP-heptose:LPS heptosyltransferase I, an enzyme of LPS inner core region biosynthesis. LPS, composed of lipid A, a core region, and O antigen, is found in the outer membrane of Gram-negative bacteria .
Glutaredoxin-like protein NrdH (GlrX_NrdH)
Type: Family

Glutaredoxins , also known as thioltransferases (disulphide reductases), are small proteins of approximately one hundred amino-acid residues which utilise glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system .

Glutaredoxin functions as an electron carrier in the glutathione-dependent synthesis of deoxyribonucleotides by the enzyme ribonucleotide reductase. Like thioredoxin (TRX), which functions in a similar way, glutaredoxin possesses an active centre disulphide bond . It exists in either a reduced or an oxidized form where the two cysteine residues are linked in an intramolecular disulphide bond. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH ->GSH reductase ->GSH ->GRX ->protein substrates . By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress.

Glutaredoxin has been sequenced in a variety of species. On the basis of extensive sequence similarity, it has been proposed that Vaccinia virus protein O2L is most probably a glutaredoxin. Finally, it must be noted that Bacteriophage T4 thioredoxin seems also to be evolutionary related. In position 5 of the pattern T4 thioredoxin has Val instead of Pro.

NrdH-redoxin is a representative of a class of small redox proteins that contain a conserved CXXC motif and are characterised by a glutaredoxin-like amino acid sequence and thioredoxin-like activity profile. Unlike other the glutaredoxins to which it is most closely related, NrdH apparently does not interact with glutathione/glutathione reductase, but rather with thioredoxin reductase to catalyze the reduction of ribonucleotide reductase .
ADP-heptose--LPS heptosyltransferase 2 (RfaF)
Type: Family

This family consists of ADP-heptose--LPS heptosyltransferase 2, an enzyme of the lipopolysaccharide (LPS) inner core region biosynthesis. LPS, composed of lipid A, a core region, and O antigen, is found in the outer membrane of Gram-negative bacteria .
Glutaredoxin-like protein, YruB (GlrX_YruB)
Type: Family

Glutaredoxins , also known as thioltransferases (disulphide reductases), are small proteins of approximately one hundred amino-acid residues which utilise glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system .

Glutaredoxin functions as an electron carrier in the glutathione-dependent synthesis of deoxyribonucleotides by the enzyme ribonucleotide reductase. Like thioredoxin (TRX), which functions in a similar way, glutaredoxin possesses an active centre disulphide bond . It exists in either a reduced or an oxidized form where the two cysteine residues are linked in an intramolecular disulphide bond. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH ->GSH reductase ->GSH ->GRX ->protein substrates . By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress.

Glutaredoxin has been sequenced in a variety of species. On the basis of extensive sequence similarity, it has been proposed that Vaccinia virus protein O2L is most probably a glutaredoxin. Finally, it must be noted that Bacteriophage T4 thioredoxin seems also to be evolutionary related. In position 5 of the pattern T4 thioredoxin has Val instead of Pro.

This glutaredoxin-like protein family contains the conserved CxxC motif and includes the Clostridium pasteurianum protein YruB which has been cloned from a rubredoxin operon . Somewhat related to NrdH, it is unknown whether this protein actually interacts with glutathione/glutathione reducatase, or, like NrdH, some other reductant system.
RfaE bifunctional protein, domain I (RfaE_dom_I)
Type: Domain

RfaE is a protein involved in the biosynthesis of ADP-L-glycero-D-manno-heptose, a precursor for LPS inner core biosynthesis. RfaE is a bifunctional protein in Escherichia coli, and separate proteins in some other genome. The longer, N-terminal domain I (this family) is suggested to act in D-glycero-D-manno-heptose 1-phosphate biosynthesis, while domain II (

) adds ADP to yield ADP-D-glycero-D-manno-heptose .
RfaE bifunctional protein, domain II (RfaE_dom_II)
Type: Domain

RfaE is a protein involved in the biosynthesis of ADP-L-glycero-D-manno-heptose, a precursor for LPS inner core biosynthesis. RfaE is a bifunctional protein in Escherichia coli, and separate proteins in some other genome. Domain I (

) is suggested to act in D-glycero-D-manno-heptose 1-phosphate biosynthesis, while domain II (this family) adds ADP to yield ADP-D-glycero-D-manno-heptose .
Glutaredoxin-like protein, actinobacteria (GlrX_actino)
Type: Family

Glutaredoxins , also known as thioltransferases (disulphide reductases), are small proteins of approximately one hundred amino-acid residues which utilise glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system .

Glutaredoxin functions as an electron carrier in the glutathione-dependent synthesis of deoxyribonucleotides by the enzyme ribonucleotide reductase. Like thioredoxin (TRX), which functions in a similar way, glutaredoxin possesses an active centre disulphide bond . It exists in either a reduced or an oxidized form where the two cysteine residues are linked in an intramolecular disulphide bond. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH ->GSH reductase ->GSH ->GRX ->protein substrates . By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress.

Glutaredoxin has been sequenced in a variety of species. On the basis of extensive sequence similarity, it has been proposed that Vaccinia virus protein O2L is most probably a glutaredoxin. Finally, it must be noted that Bacteriophage T4 thioredoxin seems also to be evolutionary related. In position 5 of the pattern T4 thioredoxin has Val instead of Pro.

This family of glutaredoxin-like proteins is limited to the Actinobacteria and contains the conserved CxxC motif.
Lipopolysaccharide heptosyltransferase III, putative (LipoPS_heptosylTferase-III)
Type: Family

This family consists of examples of the putative ADP-heptose:LPS heptosyltransferase III, an enzyme of the lipopolysaccharide (LPS) inner core region biosynthesis. LPS, composed of lipid A, a core region, and O antigen, is found in the outer membrane of Gram-negative bacteria. This enzyme may be less widely distributed than heptosyltransferases I and II.
ABC transporter, ATP-binding/permease protein (ABC_MsbA_ATP-bd)
Type: Family

This protein is related to a Proteobacterial ATP transporter that exports lipid A and to eukaryotic P-glycoproteins .
Cell division protein ZipA (Cell_div_ZipA)
Type: Family

Cell division in bacteria is a complex process driven by the septal ring, a membrane-associated cytoskeletal element that directs the formation of the septum . Central to formation of the septal ring, and hence cell division itself, is the tubulin-like GTPase protein FtsZ which is the first cell division component to specifically accumulate at the division site. Here it self-assembles into a ring-like polymer structure associated with the inner surface of the cytoplasmic membrane, providing a scaffold to recruit other members of the septal ring.

This entry represents the bacterial cell division protein ZipA. ZipA is one of the first proteins recruited to the division site after FtsZ, which it directly binds, and is essential for cell division and viability in Escherichia coli. ZipA has been shown to The protein contains five distinct regions. The N terminus contains a short hydrophobic regions which anchors the protein to the cytoplasmic membrane. This is followed by short basic and acidic regions, and a longer proline-rich region. The C-terminal domain interacts with FtsZ through hydrophobic interactions involving exposed non-polar residues, and forms a six-stranded β sheet packed against three α helices . Since ZipA is anchored to the cytoplasmic membrane while binding FtsZ, it has been speculated that the function of ZipA may be to link the membrane with the FtsZ rings, to stabilise or organise the FtsZ rings, or to link invagination of the membrane to constriction of the FtsZ ring during septation. ZipA has been shown to induce association of FtsZ protofilaments into arrays of long thick bundles in vitro.
Lipid A biosynthesis lauroyl/palmitoleoyl acyltransferase (Lipid_A_LpxL_LpxP)
Type: Family

Bacterial lipopolysachharides (LPS) are glycolipids that make up the outer monolayer of the outer membranes of most Gram-negative bacteria. Though LPS moleculesare variable, they all show the same general features: an outer polysaccharide which is attached to the lipid component, termed lipid A . The polysaccharide component consists of a variable repeat-structure polysaccharide known as the O-antigen, and a highly conserved short core oligosaccharide which connects the O-antigen to lipid A. Lipid A is a glucosamine-based phospholipid that makes up the membrane anchor region of LPS . The structure of lipid A is relatively invariant between species, presumably reflecting its fundamental role in membrane integrity. Recognition of lipid A by the innate immune system can lead to a response even at picomolar levels. In some genera, such as Neisseria and Haemophilus, lipooligosaccharides (LOS) are the predominant glycolipids . These are analogous to LPS except that they lack O-antigens, with the LOS oligosaccharide structures limited to 10 saccharide units.

This entry represents a narrow clade of acyltransferases, nearly all of which transfer a lauroyl group to KDO2-lipid IV-A, a lipid A precursor; these proteins are termed lipid A biosynthesis lauroyl acyltransferase, lpxL. An exception is a closely related paralog of E. coli lpxL, LpxP, which acts in cold shock conditions by transferring a palmitoleoyl rather than lauroyl group to the lipid A precursor. Members of this family are homologous to the family of acyltransferases responsible for the next step in lipid A biosynthesis .
Lipid A biosynthesis myristoyltransferase (Lipid_A_MsbB)
Type: Family

Bacterial lipopolysachharides (LPS) are glycolipids that make up the outer monolayer of the outer membranes of most Gram-negative bacteria. Though LPS moleculesare variable, they all show the same general features: an outer polysaccharide which is attached to the lipid component, termed lipid A . The polysaccharide component consists of a variable repeat-structure polysaccharide known as the O-antigen, and a highly conserved short core oligosaccharide which connects the O-antigen to lipid A. Lipid A is a glucosamine-based phospholipid that makes up the membrane anchor region of LPS . The structure of lipid A is relatively invariant between species, presumably reflecting its fundamental role in membrane integrity. Recognition of lipid A by the innate immune system can lead to a response even at picomolar levels. In some genera, such as Neisseria and Haemophilus, lipooligosaccharides (LOS) are the predominant glycolipids . These are analogous to LPS except that they lack O-antigens, with the LOS oligosaccharide structures limited to 10 saccharide units.

This family consists of Lipid A biosynthesis myristoyltransferase (LpxM, also known as MsbB) in Escherichia coli and closely related proteins in other species. LpxM is homologous to HtrB (

) and acts immediately after it in the biosynthesis of KDO-2 lipid A (also called Re LPS and Re endotoxin). These two enzymes act after creation of KDO-2 lipid IV-A by addition of the KDO sugars.
Cell division protein FtsL (Cell_div_FtsL)
Type: Family

FtsL is one of the later proteins active in cell division septum formation. FtsL is small, low in complexity, and highly divergent .
Probable peptidoglycan glycosyltransferase RodA/MrdB (RodA/MrdB)
Type: Family

Treponema pallidum RodA and Escherichia coli MrdB are probable peptidoglycan polymerases that are essential for cell wall elongation . RodA is a member of the FtsW/RodA/SpoVE family. It is found only in species with rod (or spiral) shapes. RodA is required for the maintenance of the rod cell shape and is essential for the elongation of the lateral wall of the cell . In Escherichai coli, the rodA and pbpA genes occur in the same operon, and RodA is required for the expression of the enzymatic activity of the penicillin-binding protein 2 (PbpA) .
Lipoprotein releasing system, ATP-binding protein (LolD_lipo_ATP-bd)
Type: Family

This entry represents LolD, a member of the ABC transporter family. LolD is involved in localization of lipoproteins in some bacteria. It works with a transmembrane protein LolC, which in some species is a paralogous pair LolC and LolE. Depending on the residue immediately following the modified N-terminal Cys residue, the nascent lipoprotein may be carried further by LolA and LolB to the outer membrane, or remain at the inner membrane . The LolCDE complex differs mechanistically from all other ABC transporters as it is not involved in the transmembrane transport of substrates .
Lipoprotein-releasing system transmembrane protein LolC/E (LolCE_TM)
Type: Family

This entry describes the LolC protein, and its paralog LolE found in some species. These proteins are homologous to permease proteins of ABC transporters. In some species, two paralogs occur, designated LolC and LolE. In others, a single form is found and tends to be designated LolC .

The LolCDE complex releases lipoproteins from the inner membrane, thereby initiating lipoprotein sorting to the outer membrane. The LolCDE complex in Escherichia coli is composed of two copies of an ATPase subunit, LolD, and one copy each of integral membrane subunits LolC and LolE . The LolCDE complex releases the lipoproteins in the periplasm, where they form a complex with LolA. The LolA-lipoprotein complex crosses the periplasm to reach the outer membrane, where LolB incorporates the lipoprotein into the outer membrane. LolA is involved in the interaction with membrane subunit LolC, whereas no interaction has been observed with LolE. This observations indicate that LolC and LolE may play different roles in the lipoprotein transfer despite their structural resemblance .
Lipoprotein-releasing system transmembrane protein LolE, gammaproteobacteria type (LolE_gammaproteobact)
Type: Family

This protein is part of an unusual ABC transporter complex that releases lipoproteins from the periplasmic side of the bacterial inner membrane, rather than transport any substrate across the inner membrane. In some species, the permease-like transmembrane protein is represented by two paralogs, LolC and LolE, both in the LolCDE complex .
Stage V sporulation protein D (SpoVD_pbp)
Type: Family

This entry describes the SpoVD family of homologues of the cell division protein FtsI, a penicillin binding protein. This family is restricted to Bacillus subtilis and related Gram-positive species with known or suspected endospore formation capability. In these species, the functional equivalent of FtsI is desginated PBP-2B, a paralog of SpoVD.
Bacteriophage phiJL001, Gp84 (Phage_phiJL001_Gp84)
Type: Family

This entry describes bacteriophage phiJL001 Gp84 and related proteins in other bacteriophage and prophage regions of bacterial genomes. Homologues are also found in Gene Transfer Agents (GTA) , including ORFg13 (RCAP_rcc01696) of the GTA of Rhodobacter capsulatus (Rhodopseudomonas capsulata) [[see Fig.1, in

]. The function of these proteins is unkown

An apparent exception is Wolbachia pipientis wMel, a bacterial endosymbiont of the fruit fly, which has several candidate phiJL001 Gp84 related-genes physically separate from obvious prophage regions.