SII-SWORD/CoKE huggingface dataset:
RNA polymerase sigma-70, Myxococcus xanthus (RNA_pol_sigma70_MYXXA)
Type: Family

The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme . RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.

With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors .

The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors .

This entry describes sigma-70 factors in Myxococcus xanthus (strain DK 1622) and in other members of the Mycococcales. Each of the six members in M. xanthusis is encoded near a gene for a predicted serine/threonine kinase. Members of this family show sequence similarity to members of Pfam family

(region 4 of sigma-70 like sigma-factors), a helix-turn-helix family in which trusted and noise cutoffs deliberately are set artificially high and which therefore has many false negatives.
Trp biosynthesis associated, conserved hypothetical membrane protein (Trp_synth-assoc_CHP)
Type: Family

Members of this family are predicted transmembrane proteins with four membrane-spanning helices. Members are found in the Actinobacteria (Mycobacterium, Corynebacterium, Streptomyces), always associated with genes for tryptophan biosynthesis.
Conserved hypothetical protein CHP02241 (CHP02241)
Type: Family

This entry consists of uncharacterised proteins. All members so far represent bacterial genes found in apparent phage or otherwise laterally transferred regions of the chromosome. Tentatively identified neighbouring proteins tend to be phage tail region proteins. In some species, including Photorhabdus luminescens subsp. laumondii TTO1, several members of this family may be encoded near each other.
Uncharacterised protein family, phage tail-like (Unchr_phage_tail-like)
Type: Domain

This entry describes a region of sequence similarity shared by a number of uncharacterised proteins in bacterial genomes, including Geobacter sulfurreducens PCA, Rhizobium loti (Mesorhizobium loti), Streptomyces coelicolor (strain A3(2)), Gloeobacter violaceus PCC 7421, and Myxococcus xanthus. In all cases, the genomic region resembles a phage tail region, based on tentative identifications of neighbouring genes. A region of this domain resembles a region of

, another phage tail protein model.
Conserved hypothetical protein CHP02243 (CHP02243)
Type: Family

This family consists of a large, conserved hypothetical protein in phage tail-like regions of at least six bacterial genomes: Gloeobacter violaceus PCC 7421, Geobacter sulfurreducens PCA, Streptomyces coelicolor (strain A3(2)), Streptomyces avermitilis MA-4680, Rhizobium loti (Mesorhizobium loti), and Myxococcus xanthus. The function is unknown.
Myxococcus xanthus double-CXXCG motif (Gmx_para_CXXCG)
Type: Family

This entry consists of at least 10 paralogous proteins from Myxococcus xanthus that lack detectable sequence similarity to any other protein family. An imperfectly conserved CXXCG motif, a probable binding site, appears twice in the multiple sequence alignment.
Myxococcus xanthus paralogous protein 2265 (Mxa_paralog_2265)
Type: Family

This family consists of a set of at least 17 paralogous proteins in Myxococcus xanthus (strain DK 1622). Members are about 200 amino acids in length. No other homologuess are known; the function is unknown.
PilZ domain, Myxococcales-type (PilV_Myxo-type)
Type: Domain

The ubiquitous bacterial second messenger cyclic-di-GMP (c-di-GMP) is associated with the regulation of biofilm formation, the control of exopolysaccharide synthesis, flagellar- and pili-based motility, gene expression, interactions of bacteria with eukaryotic hosts and multicellular behaviour in diverse bacteria. This second messenger binds to PliZ domains from cytoplasmic receptors through its RXXXR and [D/N]hSXXG motifs . However, some PilZ-related domains lack these motifs and do not bind c-di-GMP. The crystal structure, at 1.7 A, of a PilZ domain::c-di-GMP complex from Vibrio cholerae shows c-di-GMP contacting seven of nine strongly conserved residues. Binding of c-di-GMP causes a conformational switch whereby the C- and N-terminal domains are brought into close opposition forming a new allosteric interaction surface that spans these domains and the c-di-GMP at their interface . Structural and sequence analysis of PilZ-related domains allow the description of three types of domains, the canonical PilZ domain (represented in this entry), whose structure includes a six-stranded β-barrel and a C-terminal α helix, an atypical PilZ domain containing two additional α helices and forms tetramers, and divergent PilZ-related domains, which include the PilZ protein and the YcgR N-terminal domains (PilZN and PilZNR). PilZN-type domains are evolutionarily related to PliZ domains and are found fused to the canonical PilZ domains in specific taxa, such as spirochetes, actinobacteria, aquificae, cellulose-degrading clostridia, and deltaproteobacteria .

Some examples of proteins containing this domain are BcsA subunits of bacterial cellulose synthases and flagellar brake protein YcgR (see

) . c-di-GMP binding to PilZ brings about conformational changes in the protein that stabilise the bound ligand and probability initiates the downstream signal transduction cascade. In the case of YcgR, c-di-GMP binding regulates flagellum-based motility in a c-di-GMP-dependent manner (see

) . The association of the PilZ domain with a variety of other domains, including likely components of bacterial multidrug secretion system, could provide clues to multiple functions of the c-di-GMP in bacterial pathogenesis and cell development.

This entry represents a PilZ domain found mainly in Myxococcales.
DUSAM domain (DUSAM_dom)
Type: Domain

This domain is found in at least eight paraloguous proteins in Myxococcus xanthus and six in Stigmatella aurantiaca DW4/3-1, both members of Myxococcales order within the Deltaproteobacteria. The function is unknown. Some proteins consist of two copies of the domain. This domain is hereby named DUSAM, DUplication in Stigmatella And Myxococcus.
Myxococcus xanthus paralogous protein 2268 (Mxa_paralog_2268)
Type: Family

This family consists of at least 8 paralogs in Myxococcus xanthus, a member of the Deltaproteobacteria. The function is unknown.
Conserved hypothetical protein CHP02269, MYXXA (CHP02269_MYXXA)
Type: Family

This family represents a group of uncharacterised proteins from Myxococcales, including CHP02269, MYXXA from Stigmatella aurantiaca and at least 9 paralogues in Myxococcus xanthus. One appears truncated toward the N terminus; the others are predicted lipoproteins. The function is unknown.
Lytic transglycosylase MltB (Lytic_transglycosylase_MltB)
Type: Family

This family consists of lytic murein transglycosylases (murein hydrolases) related to MltB (

), which is a 38kDa membrane-bound lipoprotein in Escherichia coli. The N-terminal region of this protein contains a lipoprotein-processing site which is conserved in about half the members of this family. Proteolytic cleavage of MltB produces a fully-active, soluble form of this enzyme known as Slt35 (for soluble lytic transglycosylase). This enzyme catalyzes the cleavage of the glycosidic bonds between N-acetylmuramic acid and N-acetylglucosamine residues in peptidoglycan. Its physiological role is unknown as deletion of the gene shows no obvious phenotype , though it has been suggested to play a role in recycling of muropeptides during cell elongation and/or cell division.

The Slt35 enzyme is a monomer with an ellipsoid shape and is composed of three distinct domains known as the alpha, beta and core domains . The alpha domain contains mainly α-helices, while the beta domain consists of a five-stranded antiparallel β-sheet flanked by a short α-helix. The core domain is sandwiched between the alpha and beta domains and its fold is similar to that of lysozyme, but contains a single metal ion binding site in a helix-loop-helix module that is similar to the eukaryotic EF-hand calcium-binding fold, though in this case the loop is slightly longer than usual. Binding of Ca(2+) to this EF hand motif has been shown to be important for thermal stability of the protein . The substrate binding sites are found in the cleft formed by the core domain of the enzyme .

Members of this family do not contain the putative peptidoglycan binding domain described by

, which is associated with several other classes of bacterial cell wall lytic enzymes.
Alpha-L-glutamate ligase-related protein (RimK-rel_E_lig)
Type: Family

Members of this protein family contain a region of homology to the RimK family of alpha-L-glutamate ligases (

), various members of which modify the Glu-Glu C terminus of ribosomal protein S6, or tetrahydromethanopterin, or a form of coenzyme F420 derivative. Members of this family are found so far in various Vibrio and Pseudomonas species and some other gamma and beta Proteobacteria. The function is unknown.
Cytochrome C oxidase subunit II, transmembrane domain (Cyt_c_oxidase_su2_TM_dom)
Type: Domain

Cytochrome c oxidase (

) is an oligomeric enzymatic complex which is a component of the respiratory chain and is involved in the transfer of electrons from cytochrome c to oxygen. In eukaryotes this enzyme complex is located in the mitochondrial inner membrane; in aerobic prokaryotes it is found in the plasma membrane. The enzyme complex consists of 3-4 subunits (prokaryotes) to up to 13 polypeptides (mammals).

Subunit 2 (CO II) transfers the electrons from cytochrome c to the catalytic subunit 1. It contains two adjacent transmembrane regions in its N terminus and the major part of the protein is exposed to the periplasmic or to the mitochondrial intermembrane space, respectively. CO II provides the substrate-binding site and contains a copper centre called Cu(A) (see

), probably the primary acceptor in cytochrome c oxidase. An exception is the corresponding subunit of the cbb3-type oxidase which lacks the copper A redox-centre. Several bacterial CO II have a C-terminal extension that contains a covalently bound haem c.

The N-terminal domain of cytochrome C oxidase contains two transmembrane α-helices .
Pseudouridine synthase, TruD, insertion domain (PsdUridine_synth_TruD_insert)
Type: Domain

Pseudouridine synthases catalyse the isomerisation of uridine to pseudouridine (Psi) in a variety of RNA molecules, and may function as RNA chaperones. Pseudouridine is the most abundant modified nucleotide found in all cellular RNAs. There are four distinct families of pseudouridine synthases that share no global sequence similarity, but which do share the same fold of their catalytic domain(s) and uracil-binding site and are descended from a common molecular ancestor. The catalytic domain consists of two subdomains, each of which has an α+β structure that has some similarity to the ferredoxin-like fold (note: some pseudouridine synthases contain additional domains). The active site is the most conserved structural region of the superfamily and is located between the two homologous domains. These families are :

Pseudouridine synthase I, TruA.

Pseudouridine synthase II, TruB, which contains and additional C-terminal PUA domain.

Pseudouridine synthase RsuA. RluB, RluE and RluF are also part of this family.

Pseudouridine synthase RluA. TruC, RluC and RluD belong to this family.

Pseudouridine synthase TruD, which has a natural circular permutation in the catalytic domain, as well as an insertion of a family-specific α+β subdomain.

Pseudouridine synthase TruD modifies uracil-13 in tRNA . TruD belongs to a large family of pseudouridine synthases present in all kingdoms of life . It folds into a V-shaped molecule with an RNA-binding cleft formed between its two domains: a catalytic domain and an insertion domain. The catalytic domain differs in sequence but is structurally very similar to the catalytic domain of other pseudouridine synthases. The insertion (or TRUD) domain displays an α/β structure that forms a compact fold titled away from the catalytic domain to create a deep cleft in TruD which is lined with basic residues from each domain. The insertion domain is characterised by two conserved sequence motifs that form a part of the hydrophobic core, as well as by large insertions at several specific sites that are seen in many archaeal and eukaryotic homologues. The insertion domain is likely to be involved in substrate recognition and may represent a RNA binding module .
ATP-grasp fold (ATP-grasp)
Type: Domain

The ATP-grasp superfamily currently includes 17 groups of enzymes, catalysing ATP-dependent ligation of a carboxylate containing molecule to an amino or thiol group-containing molecule . They contribute predominantly to macromolecular synthesis. ATP-hydrolysis is used to activate a substrate. For example, DD-ligase transfers phosphate from ATP to D-alanine on the first step of catalysis. On the second step the resulting acylphosphate is attacked by a second D-alanine to produce a DD dipeptide following phosphate elimination .

The ATP-grasp domain contains three conserved motifs, corresponding to the phosphate binding loop and the Mg(2+) binding site . The fold is characterised by two α-β subdomains that grasp the ATP molecule between them. Each subdomain provides a variable loop that forms part of the active site, with regions from other domains also contributing to the active site, even though these other domains are not conserved between the various ATP-grasp enzymes .
Acetyl-coenzyme A carboxyltransferase, N-terminal (COA_CT_N)
Type: Domain

Acetyl-coenzyme A carboxylase (

) (ACC), a member of the biotin-dependent enzyme family, catalyses the formation of malonyl-coenzyme A (CoA) and regulates fatty acid biosynthesis and oxidation. Biotin-dependent carboxylase enzymes perform a two step reaction: enzyme-bound biotin is first carboxylated by bicarbonate and ATP and the carboxyl group temporarily bound to biotin is subsequently transferred to an acceptor substrate such as acetyl-CoA. The carboxyltransferase domain performs the second part of the reaction .

The N- and C-terminal regions of the carboxyltransferase domain share similar polypeptide backbone folds, with a central β-β-α superhelix . The CoA molecule is mostly associated with the N subdomain. In bacterial acetyl coenzyme A carboxylase the N and C subdomains are encoded by two different polypeptides.

This entry represents the N-terminal subdomain and contains the bacterial ACC beta-subunit.
Acetyl-coenzyme A carboxyltransferase, C-terminal (COA_CT_C)
Type: Domain

Acetyl-coenzyme A carboxylase (

) (ACC), a member of the biotin-dependent enzyme family, catalyses the formation of malonyl-coenzyme A (CoA) and regulates fatty acid biosynthesis and oxidation. Biotin-dependent carboxylase enzymes perform a two step reaction: enzyme-bound biotin is first carboxylated by bicarbonate and ATP and the carboxyl group temporarily bound to biotin is subsequently transferred to an acceptor substrate such as acetyl-CoA. The carboxyltransferase domain performs the second part of the reaction .

The N- and C-terminal regions of the carboxyltransferase domain share similar polypeptide backbone folds, with a central β-β-α superhelix . The CoA molecule is mostly associated with the N subdomain. In bacterial acetyl coenzyme A carboxylase the N and C subdomains are encoded by two different polypeptides.

The acetyl-coenzyme A carboxyltransferase domain is also found in the following enzymes:

Methylcrotonyl-CoA carboxylase beta chain, mitochondrial precursor.

Glutaconyl-CoA decarboxylase alpha subunit.

Propionyl-CoA carboxylase beta chain (PCCase).

This domain is the C subdomain and recognises also the alpha-subunit of bacterial ACC.
Biotin carboxylation domain (Biotin_carboxylation_dom)
Type: Domain

Biotin-dependent carboxylase enzymes perform a two step reaction. Enzyme-bound biotin is first carboxylated by bicarbonated and ATP and the carboxyl group temporarily bound to biotin is subsequently transferred to an acceptor substrate such as pyruvate or acetyl-CoA. The first step is mediated by the BC domain common to all biotin-dependent carboxylases . The BC domain can be divided in three subdomains (N-terminal, central and C-terminal). The N-terminal region provides part of the active site; the central region corresponds to the ATP-grasp domain, which is common to many ATP-dependent enzymes involved in macromolecular synthesis . The ATP-grasp module directly binds the ATP molecule. The C-terminal subdomain is involved in dimer formation.

Several structure of the BC domain have been solved . The central module is splayed significantly away from the main body of the domain and is able to rotate of approximately 45 degree upon nucleotide binding thereby closing off the active site pocket .
Peptidase M16, N-terminal (Pept_M16_N)
Type: Domain

This entry represents an N-terminal domain found in metallopeptidases and non-peptidase homologues belonging to MEROPS peptidase family M16 (clan ME), subfamilies M16A, M16B and M16C. Members of this group of proteins include:

Insulinase, insulin-degrading enzyme (

)

Mitochondrial processing peptidase alpha subunit, (Alpha-MPP,

)

Pitrilysin, Protease III precursor (

)

Nardilysin (

)

Ubiquinol-cytochrome C reductase complex core protein I,mitochondrial precursor (

)

Coenzyme PQQ synthesis protein F (

)

These proteins do not share many regions of sequence similarity; the most noticeable is in the N-terminal section. This region includes a conserved histidine followed, two residues later by a glutamate and another histidine. In pitrilysin, it has been shown that this H-x-x-E-H motif is involved in enzymatic activity; the two histidines bind zinc and the glutamate is necessary for catalytic activity.

The proteins classified as non-peptidase homologues either have been found experimentally to be without peptidase activity, or lack amino acid residues that are believed to be essential for the catalytic activity.
Thiamine pyrophosphate enzyme, TPP-binding (TPP_enzyme_TPP-bd)
Type: Domain

A number of enzymes require thiamine pyrophosphate (TPP) (vitamin B1) as a cofactor. It has been shown that some of these enzymes are structurally related. The thiamin diphosphate-binding fold comprises two different functional modules, the pyridine-binding (Pyr) and pyrophosphate-binding (PP) modules. This represents the TPP binding domain which localizes at the C-terminal of TPP enzymes and in some members has been described as the PP-binding module.
Glutaredoxin active site (GLR_AS)
Type: Active_site

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 entry represents the Glutaredoxin active site.
Translation elongation factor P (Transl_elongation_fac_P)
Type: Family

Members of this family possess translation elongation factor activity. They have been shown to stimulate efficient translation and peptide-bond synthesis on native or reconstituted 70S ribosomes in vitro, possibly indirectly by altering the affinity of the ribosome for aminoacyl-tRNA, thus increasing their reactivity as acceptors for peptidyl transferase (by similarity) . This family does not include members of

, an EFP-like protein of certain gammaproteobacteria.
Magnesium-chelatase, subunit H (BchH)
Type: Family

This entry represents the H subunit of the magnesium chelatase complex responsible for magnesium insertion into the protoporphyrin IX ring in the biosynthesis of both chlorophyll and bacteriochlorophyll. In chlorophyll-utilizing species, this gene is known as ChlH, while in bacteriochlorophyll-utilizing spoecies it is called BchH. Subunit H is the largest (~140kDa) of the three subunits (the others being BchD/ChlD and BchI/ChlI), and is known to bind protoporphyrin IX. Subunit H is homologous to the CobN subunit of cobaltochelatase and by anology with that enzyme, subunit H is believed to also bind the magnesium ion which is inserted into the ring. In conjunction with the hydrolysis of ATP by subunits I and D, a conformation change is believed to happen in subunit H causing the magnesium ion insertion into the distorted protoporphyrin ring .