SII-SWORD/CoKE huggingface dataset:
DNA polymerase III, subunit gamma/ tau, N-terminal (DNA_pol_III_sug/sutau_N)
Type: Domain

This entry represents the well-conserved first N-terminal domain of DnaX (also known as DNA polymerase III subunit gamma/tau), approx. 365 aa. The full-length product of the dnaX gene in Escherichia coli encodes the DNA polymerase III tau subunit. A translational frameshift leads to early termination and a truncated protein subunit gamma, about 1/3 shorter than tau and present in roughly equal amounts. This frameshift mechanism is not necessarily universal for species with DNA polymerase III but appears conserved in the extreme thermophile Thermus thermophilus.

This domain is also found in protein STICHEL and STICHEL-like (STI) from Arabidopsis, which share sequence similarity with DNA polymerase III gamma/tau subunits . STI is nuclear-localized and does not participate in genome duplication; it is a key regulator of trichome branching through an endoreduplication-independent pathway .
Glucosylglycerol-phosphate synthase (Gluc_glyc_Psyn)
Type: Family

Glucosylglycerol-phosphate synthase catalyses the key step in the biosynthesis of the osmolyte glucosylglycerol. It is known in several cyanobacteria and in Pseudomonas anguilliseptica. The enzyme is closely related to the alpha,alpha-trehalose-phosphate synthase, likewise involved in osmolyte biosynthesis, of Escherichia coli and many other bacteria. A close homologue from Xanthomonas campestris is excluded from this family.
Glucosylglycerol-phospate 3-phosphatase (GGPPase)
Type: Family

Proteins in this family are glucosylglycerol-phosphate phosphatases, with the gene symbol stpA (Salt Tolerance Protein A). A motif characteristic of acid phosphatases is found, but otherwise this family shows little sequence similarity to other phosphatases. This enzyme acts on the glucosylglycerol phosphate, product of glucosylglycerol phosphate synthase and immediate precursor of the osmoprotectant glucosylglycerol .
Alpha,alpha-trehalose-phosphate synthase (Trehalose_OtsA)
Type: Family

This enzyme catalyzes the key, penultimate step in biosynthesis of trehalose, a compatible solute made as an osmoprotectant in some species in all three domains of life. The gene symbol OtsA stands for osmotically regulated trehalose synthesis A. Trehalose helps protect against both osmotic and thermal stresses, and is made from two glucose subunits. This entry excludes glucosylglycerol-phosphate synthase, an enzyme of an analogous osmoprotectant system in many cyanobacterial strains. This entry does not identify archaeal examples, as they are more divergent than glucosylglycerol-phosphate synthase. Sequences that score in the gray zone between the trusted and noise cut offs include a number of yeast multidomain proteins in which the N-terminal domain may be functionally equivalent to this family. The gray zone also includes the OtsA of Cornyebacterium glutamicum (and related species), shown to be responsible for synthesis of only trace amounts of trehalose while the majority is synthesized by the TreYZ pathway; the significance of OtsA in this species is unclear (see ).
Maltooligosyl trehalose synthase (Trehalose_TreY)
Type: Family

This family describes the enzyme TreY. Maltooligosyl trehalose synthase (MTSase, TreY) and maltooligosyl trehalose trehalohydrolase (MTHase, TreZ) work together to produce trehalose. MTSase is responsible for converting the alpha-1,4-glucosidic linkage to an alpha,alpha-1,1-glucosidic linkage at the reducing end of the maltooligosaccharide through an intramolecular transglucosylation reaction, while MTHase hydrolyzes the penultimate alpha-1,4 linkage of the reducing end, resulting in the release of trehalose . The TreYZ pathway of trehalose biosynthesis is an alternative to the OtsAB pathway that generates trehalose from glucose and glucose-6-phosphate . Trehalose may be incorporated into more complex compounds but is best known as compatible solute. It is one of the most effective osmoprotectants, and unlike the various betaines does not require nitrogen for its synthesis.
Malto-oligosyltrehalose trehalohydrolase (Trehalose_TreZ)
Type: Family

Members of this family are the trehalose biosynthetic enzyme malto-oligosyltrehalose trehalohydrolase, formally known as 4-alpha-D-{(1->4)-alpha-D-glucano}trehalose trehalohydrolase (

). It is the TreZ protein of the TreYZ pathway for trehalose biosynthesis, and alternative to the OtsAB system.
Trehalose-6-phosphate hydrolase (Trehalose_TreC)
Type: Family

Trehalose is a glucose disaccharide that serves in many biological systems as a compatible solute for protection against hyperosmotic and thermal stress. This family describes trehalose-6-phosphate hydrolase, product of the treC (or treA) gene, which is often found together with a trehalose uptake transporter and a trehalose operon repressor .
Trehalose operon transcriptional repressor (TreR)
Type: Family

This family consists of repressors of the GntR family typically associated with trehalose utilization operons. Trehalose is imported as trehalose-6-phosphate and then hydrolyzed by alpha,alpha-phosphotrehalase to glucose and glucose-6-P. This family includes repressors mostly from Gram-positive lineages (such as TreR from Bacillus subtilis) and does not include the TreR from Escherichia coli.
Trehalose operon repressor (Trehalos_R_gpbac)
Type: Family

Trehalose is a non-reducing disaccharide which can be used as both a carbon source and an osmoprotectant in bacteria. Trehalose uptake into the cytoplasm occurs via a trehalose-specific phosphotransferase system which phosphorylates trehalase to trehalose-6-phosphate (Tre6P) during transport into the cytoplasm, and a hydrolase which hydrolyses Tre6P to glucose and glucose-6-phophate.

This entry represents LacI-type TreR, a transcriptional repressor of trehalose uptake found mainly within the gamma-proteobacteria. It does not include the GntR-type TreR's such as those found in Bacillus species. It is capable of binding both the inducer Tre6P and trehalose. Binding of trehalose does not affect the repressor's affinity for its DNA binding site, while binding Tre6P substantially reduces its affinity. The repression activity of TreR is therefore regulated by the ratio of trehalose to Tre6P within the cell . The protein is composed of two domains, an N-terminal DNA-binding helix-turn-helix domain, and a C-terminal effector-binding domain which is homologous to that of LacI. The effector-binding domain is composed of two subdomains, both of which form an α-β-α sandwich, with the effector binding site located at the interface of these subdomains . Tre6P and trehalose bind competitively to this site, with the affinity for trehalose substantially lower than that for Tre6P.
L-2,4-diaminobutyric acid acetyltransferase (Ectoine_EctA)
Type: Family

This enzyme family is the EctA of ectoine biosynthesis. Ectoine is a compatible solute, analogous to trehalose, betaines, etc., found often in halotolerant organisms. EctA is L-2,4-diaminobutyric acid acetyltransferase, also called DABA acetyltransferase .
Ectoine biosynthetic protein (Ectoine_EctB)
Type: Family

Members of this family of class III pyridoxal-phosphate-dependent aminotransferases are diaminobutyrate--2-oxoglutarate aminotransferase (

) that catalyze the first step in ectoine biosynthesis from L-aspartate beta-semialdehyde. This family is readily separated phylogenetically from enzymes with the same substrate and product but involved in other process such as siderophore (

) or 1,3-diaminopropane (

) biosynthesis. Ectoine is a compatible solute particularly effective in conferring salt tolerance.
Ectoine dioxygenase (EctD)
Type: Family

Ectoine dioxygenase EctD is involved in the biosynthesis of ectoine ((S)-2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylic acid) which is a highly soluble organic osmolyte, called compatible solute, use to avoid excessive water efflux, plasmolysis, molecular crowding of the cytoplasm, and cessation of growth in high salinity environments. It catalyses the 2-oxoglutarate-dependent selective hydroxylation of L-ectoine to yield (4S,5S)-5-hydroxyectoine .
Gamma-butyrobetaine hydroxylase-like (GBBH-like)
Type: Family

Members of this protein family are gamma-butyrobetaine hydroxylase (GBBH), both bacterial and eukaryotic. This enzyme catalyses the last step in the conversion of lysine to carnitine. Carnitine can serve as a compatible solvent in bacteria and also participates in fatty acid metabolism . The structure of human GBBH has been revealed . This entry also includes TMAEP hydroxylase (also known as 2-(trimethylammonio)ethylphosphonate dioxygenase) that does not utilise gamma-butyrobetaine as substrate in contrast to the other members of this family .
Trimethyllysine dioxygenase (Trimethyllysine_dOase)
Type: Family

Trimethyllysine dioxygenase is involved in the carnitine biosynthesis. It converts trimethyllysine (TML) into hydroxytrimethyllysine (HTML) .
Leukotriene A4 hydrolase/leucine aminopeptidase (LTA4H)
Type: Family

Members of this family represent a distinctive subset within the zinc metallopeptidases of MEROPS peptidase family M1 (aminopeptidase N, clan MA). This entry represents leukotriene A-4 hydrolase (LTA4), which in vertebrates has both epoxide hydrolase and aminopeptidase activity at the same active site . In contrast, highly homologous enzymes from yeast only have the aminopeptidase activity, showing low epoxide hydrolase activity in vitro. This is the case for leucine aminopeptidase LTA4H from budding yeast .
Peptidase M1, aminopeptidase (Pept_M1_aminopeptidase)
Type: Family

This family is a subset of the members of the zinc metallopeptidases belonging to MEROPS peptidase family M1 (aminopeptidase N, clan MA), with a single member characterised in Streptomyces lividans: aminopeptidase G . The rest of the members of this family are identified as aminopeptidase N of the actinomycete-type. The spectrum of activity may differ somewhat from the aminopeptidase N clade of Escherichia coli and most other proteobacteria, which are well separated phylogenetically within the M1 family.

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .
Peptidase M1, alanyl aminopeptidase (Peptidase_M1_pepN)
Type: Family

The M1 family of zinc metallopeptidases contains a number of distinct, well-separated clades of proteins with aminopeptidase activity. Several are designated aminopeptidase N,

, after the Escherichia coli enzyme, suggesting a similar activity profile (see

for a description of catalytic activity).

This group of zinc metallopeptidases belong to MEROPS peptidase family M1 (aminopeptidase N, clan MA); the majority are identified as alanyl aminopeptidases (proteobacteria) that are closely related to E. coli PepN and presumed to have a similar (not identical) function. Nearly all are found in proteobacteria, but members are found also in cyanobacteria, plants, and apicomplexan parasites . This family differs greatly in sequence from the family of aminopeptidases typified by Streptomyces lividans PepN (

) and from the membrane bound aminopeptidase N family in animals.

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .
Carbon-monoxide dehydrogenase, large subunit (CO_Mo_DH_lsu)
Type: Family

Carbon monoxide dehydrogenases catalyse the reversible oxidation of carbon monoxide to carbon dioxide as shown below :

CO + H(2)O + A == CO(2) + AH(2)

A variety of electron acceptors can be used by these enzymes including ferredoxin, methyl viologen and benzyl viologen. Under anaerobic conditions, carbon monoxide is utilised by a number of methanogenic archaea and acetogenic, sulphate-reducing or phototrophic bacteria. Under aerobic conditions carbon monoxide can be used as sole carbon and energy source by the carboxidotrophic bacteria, a taxonomically diverse group of obligate or facultative chemolithoautotrophic species. The anaerobic dehydrogenases are mostly nickel-containing iron-sulphur enzymes, while the The aerobic enzymes categorised so far are molybdenum-containing iron-sulphur proteins.

This entry represents the large subunit of the molybdenum-containing carbon monoxide dehydrogenase found in aerobic bacteria. This enzyme is a dimer of heterotrimers, where each heterotrimer consists of a small iron-sulphur subunit, a medium FAD-containing flavoprotein subunit and a large molybdopterin-containign subunit which contains the active site . The large subunit is divided into two domains. The N-terminal domain is composed of mainly of a five-and four-stranded mixed β-sheet and interacts with the small and medium subunits. The C-terminal domain contains a region which interacts with its counterpart in the overall dimer, providing the main dimer contact, and a β-sheet surrounded by α helices. The active site located in this subunit contains a novel dinuclear heterometal [CuSMo(=O)OH] cluster.
D-fructose-responsive transcription factor (Fruct_sucro_rep)
Type: Family

Members of this family belong the lacI helix-turn-helix family of DNA-binding transcriptional regulators. All members are from the proteobacteria. This entry includes sucrose operon repressor from Klebsiella pneumoniae and catabolite repressor/activator Cra from E. coli. Cra, also known as FruR, is a global transcription factor with both repression and activation activities, controls a large number of the genes for glycolysis and gluconeogenesis .
Acetolactate synthase, catabolic (Acetolactate_synth_catblc)
Type: Family

Acetolactate synthase is a thiamin pyrophosphate-dependent enzyme that combines two molecules of pyruvate to yield 2-acetolactate with the release of CO2. It exists in two distinct forms that have different properties, though they are clearly related . The biosynthetic form, found in plants, fungi and bacteria, is involved in the biosynthesis of branched-chain amino acids and contains non-catalytic FAD. The catabolic form is found only in some bacteria, participates in butanediol fermentation, and does not contain FAD.

This entry represents the catabolic form of acetolactate synthase, generally found in species that posses acetolactate decarboxylase, which is often encoded in the same operon. The enzyme is thought to be a homotetramer, though this has not conclusively been shown. Each monomer consists of three distinct domains, designated, starting from the N terminus, as alpha, beta and gamma . The core of the alpha and gamma domains is a six-stranded parallel β-sheet surrounded by α-helices, while the the β-domain forms a double Rossman fold. The thiamin pyrophosphate cofactor has an unusual conformation that has not been seen in other enzymes using this cofactor, including the biosynthetic form of acetolactate synthase. The active site is located in a funnel at the dimer interface, bordered by residues from all three domains.
Zinc finger, C4 DksA/TraR-type (Znf_C4_TraR)
Type: Family

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

This entry represents a putative C4-type zinc finger, DksA/TraR-type, found almost exclusively in prophage regions, actual phage, or conjugal transfer regions of the proteobacteria. Many proteins carrying this motif are small (about 70 amino acids), and appear to be homologous to but smaller than DksA (DnaK suppressor protein), found to be critical for regulating transcription of ribosomal RNA. DKsA contains a canonical zinc finger motif .
RNA polymerase-binding transcription factor DksA (DksA_RNA_pol-bd)
Type: Family

DksA (DnaK suppressor A) is originally named as a multicopy suppressor of temperature sensitivity of dnaKJ mutants . DksA is a transcription factor that acts by binding directly to the RNA polymerase (RNAP). It is required for negative regulation of rRNA expression and positive regulation of several amino acid biosynthesis promoters .
Protocatechuate 3,4-dioxygenase, beta subunit (Protocat_dOase_b)
Type: Family

Protocatechuate (3,4-dihydroxybenzene, PCA) is an aromatic compound which is a key intermediate in the degradation of the plant biopolymer lignin and other aromatic compounds. The key step of PCA degradation is the ring-cleavage performed by dioxygenases adding both atoms from molecular oxygen to specific carbon atoms within the ring. This step can be performed by two distinct mechanisms; intradiol cleavage and extradiol cleavage. In intradiol cleavage the oxygen atoms are added to the carbons carrying the hydroxyl groups, producing two carboxylate groups. In extradiol cleavage the oxygens are added to one carbon carrying a hydroxyl group and another carrying a hydrogen, resulting in the formation of a carboxylate group and an aldehydic group. For further information see .

PCA dioxygenases fall into the broader category of catechol dioxygenases. These are metalloenzymes which bind non-haem iron. The extradiol dioxygenases use Fe(II) to activate oxygen for nucleophilic attack on the aromatic substrate, while the intradiol dioxygenases use Fe(III) to activate the aromatic substrate for an electrophillic attack by oxygen .

This entry represents the beta subunit of protocatechuate 3,4-dioxygenase, an enzyme which cleaves the PCA ring by an intradiol mechanism. It is composed of two subunits, alpha (

) and beta which are highly similar in structure and are thought to share a common ancestor .
The core of each subunit is two four-stranded β-sheets that fold upon each other to form a β sandwich. The active site cavity contains the Fe(III)-binding site and is located between the two subunits. All Fe(III) ligands are contributed by the beta subunit.
Protocatechuate 3,4-dioxygenase, alpha subunit (Protocat_dOase_a)
Type: Family

Protocatechuate (3,4-dihydroxybenzene, PCA) is an aromatic compound which is a key intermediate in the degradation of the plant biopolymer lignin and other aromatic compounds. The key step of PCA degradation is the ring-cleavage performed by dioxygenases adding both atoms from molecular oxygen to specific carbon atoms within the ring. This step can be performed by two distinct mechanisms; intradiol cleavage and extradiol cleavage. In intradiol cleavage the oxygen atoms are added to the carbons carrying the hydroxyl groups, producing two carboxylate groups. In extradiol cleavage the oxygens are added to one carbon carrying a hydroxyl group and another carrying a hydrogen, resulting in the formation of a carboxylate group and an aldehydic group. For further information see .

PCA dioxygenases fall into the broader category of catechol dioxygenases. These are metalloenzymes which bind non-haem iron . The extradiol dioxygenases use Fe(II) to activate oxygen for nucleophilic attack on the aromatic substrate, while the intradiol dioxygenases use Fe(III) to activate the aromatic substrate for an electrophillic attack by oxygen .

This entry represents the alpha subunit of protocatechuate 3,4-dioxygenase, an enzyme which cleaves the PCA ring by an intradiol mechanism to produce beta-carboxy-cis,cis-muconate. The enzyme is a large aggregate of 12 protomers, each composed of two subunits, alpha and beta (

) which are highly similar in structure and are thought to share a common ancestor . The core of each subunit is two four-stranded β-sheets that fold upon each other to form a β sandwich. The active site cavity contains the Fe(III)-binding site and is located between the two subunits. All Fe(III) ligands are contributed by the beta subunit.
Pca transcription factor PcaQ (TF_PcaQ)
Type: Family

Members of this family are LysR-family transcription factors associated with operons for catabolism of protocatechuate . Members occur only in proteobacteria.
4-carboxymuconolactone decarboxylase (Decarb_PcaC)
Type: Domain

Members of this entry are 4-carboxymuconolactone decarboxylases, which catalyses the third step in the catabolism of protocatechuate (and therefore the fourth step in the catabolism of para-hydroxybenzoate, of 3-hydroxybenzoate, of vanillate, etc.). Most members of this domain are encoded within protocatechuate catabolism operons. This protein is sometimes found as a fusion protein with other enzymes of the pathway, as in Rhodococcus opacus (Nocardia opaca), Streptomyces avermitilis, and Caulobacter crescentus (Caulobacter vibrioides).