SII-SWORD/CoKE huggingface dataset:
3-carboxy-cis,cis-muconate cycloisomerase-like (Protocat_PcaB-like)
Type: Family

Proteins in this entry are 3-carboxy-cis,cis-muconate cycloisomerases (CMLEs), which catalyse the second step in the protocatechuate degradation to beta-ketoadipate and then to succinyl-CoA and acetyl-CoA. 4-hydroxybenzoate, 3-hydroxybenzoate, and vanillate can all be converted in one step to protocatechuate. All members of the seed alignment for this entry were chosen from within protocatechuate degradation operons of at least three genes of the pathway, and from genomes with the complete pathway through beta-ketoadipate .

This family also includes CreD from Streptomyces cremeus, an enzyme involved in the biosynthesis of cremeomycin, a light-sensitive o-diazoquinone with antibacterial and antiproliferative effects. CreD catalyses the formation of nitrous acid from nitrosuccinic acid synthesized from aspartate by CreE. It is a member of the aspartase/fumarase superfamily, most closely related to CMLEs .
3-oxoacid CoA-transferase, subunit B (3-oxoacid_CoA-transf_B)
Type: Domain

This entry represents the B subunit of family I CoA-transferases, which contains the conserved active-site glutamate residue. This domain forms a three-layer α-β-α sandwich where the central layer is a mixed β-sheet, against which helices pack from both sides . The active site is thought to be located at the interface of the A and B subunits and formed by loops from both subunits.

CoA-transferases catalyse the reversible transfer of of coenzyme A from CoA-thioesters to free acids, and can be divided into three families . Family I includes transferases for 3-oxoacids (

,

), short-chain fatty acids (

,

) and glutaconate (

). Most of the family I enzymes use acetyl-CoA or succinyl-CoA as CoA donors, and are composed of two separate polypeptides, subunits A and B, which generally aggregate as heterodimers or heterotetramers. The eukaryotic enzymes, however, are generally composed of a single two-domain polypetide representing a fusion of the A and B subunits. The transfer of CoA from one substrate to another occurs via a ping pong mechanism which involves the formation of thioester bond between CoA and a conserved glutamate residue at the active site of the enzyme .
3-oxoacid CoA-transferase, subunit A (3-oxoacid_CoA-transf_A)
Type: Domain

This entry represents the CoA-binding A subunit of family I CoA-transferases. This domain forms a three-layer α-β-α sandwich where the central layer is an all parallel β-sheet, against which helices pack from both sides . The active site is thought to be located at the interface of the A and B subunits and formed by loops from both subunits.

CoA-transferases catalyse the reversible transfer of of coenzyme A from CoA-thioesters to free acids, and can be divided into three families . Family I includes transferases for 3-oxoacids (

,

), short-chain fatty acids (

,

) and glutaconate (

). Most of the family I enzymes use acetyl-CoA or succinyl-CoA as CoA donors, and are composed of two separate polypeptides, subunits A and B, which generally aggregate as heterodimers or heterotetramers. The eukaryotic enzymes, however, are generally composed of a single two-domain polypetide representing a fusion of the A and B subunits. The transfer of CoA from one substrate to another occurs via a ping pong mechanism which involves the formation of thioester bond between CoA and a conserved glutamate residue at the active site of the enzyme .
Beta-ketoadipyl CoA thiolase (PcaF)
Type: Family

This entry includes beta-ketoadipyl CoA thiolase, an enzyme that acts at the end of pathways for the degradation of protocatechuate (from benzoate and related compounds) and of phenylacetic acid. This entry also includes PaaJ, a 3-oxoadipyl-CoA/3-oxo-5,6-dehydrosuberyl-CoA thiolase .
Beta-ketoadipate transcriptional regulator, PcaR/PcaU/PobR (PcaR_PcaU)
Type: Family

Members of this family are IclR-type transcriptional regulators with similar DNA binding sites, able to bind at least three different metabolites related to protocatechuate metabolism. Beta-ketoadipate is the inducer for PcaR, p-hydroxybenzoate for PobR, and protocatechuate for PcaU.
tRNA(Ile)-lysidine synthase, N-terminal (tRNA_Ile_lys_synt_N)
Type: Domain

This entry represents the N-terminal domain of lysidine-tRNA(Ile) synthetase (TilS), which ligates lysine onto the cytidine present at position 34 of the AUA codon-specific tRNA(Ile) that contains the anticodon CAU, in an ATP-dependent manner. Cytidine is converted to lysidine, thus changing the amino acid specificity of the tRNA from methionine to isoleucine. The N-terminal region contains the highly conserved SGGXDS motif, predicted to be a PP-loop motif involved in ATP binding.

The only examples in which the wobble position of a tRNA must discriminate between G and A of mRNA are AUA (Ile) vs. AUG (Met) and UGA (stop) vs. UGG (Trp). In all bacteria, the wobble position of the tRNA(Ile) recognizing AUA is lysidine, a lysine derivative of cytidine. This domain is found, apparently, in all bacteria in a single copy. Eukaryotic sequences appear to be organellar. The domain architecture of this protein is variable; some, including characterised proteins of Escherichia coli and Bacillus subtilis known to be tRNA(Ile)-lysidine synthetase, include a conserved 50-residue domain that many other members lack. This protein belongs to the ATP-binding PP-loop family. It appears in the literature and protein databases as TilS, YacA, and putative cell cycle protein MesJ (a misnomer).

The PP-loop motif appears to be a modified version of the P-loop of nucleotide binding domain that is involved in phosphate binding . Named PP-motif, since it appears to be a part of a previously uncharacterised ATP pyrophosphatase domain. ATP sulfurylases, E. coli NtrL, and B. subtilis OutB consist of this domain alone. In other proteins, the pyrophosphatase domain is associated with amidotransferase domains (type I or type II), a putative citrulline-aspartate ligase domain or a nitrilase/amidase domain. The HUP domain class (after HIGH-signature proteins, UspA, and PP-ATPase) groups together PP-loop ATPases, the nucleotide-binding domains of class I aminoacyl-tRNA synthetases, UspA protein (USPA domains), photolyases, and electron transport flavoproteins (ETFP). The HUP domain is a distinct class of α/β domain .
Precorrin-6A synthase [deacetylating] (CobF)
Type: Family

Cobalamin (vitamin B12) is a structurally complex cofactor, consisting of a modified tetrapyrrole with a centrally chelated cobalt. Cobalamin is usually found in one of two biologically active forms: methylcobalamin and adocobalamin. Most prokaryotes, as well as animals, have cobalamin-dependent enzymes, whereas plants and fungi do not appear to use it. In bacteria and archaea, these include methionine synthase, ribonucleotide reductase, glutamate and methylmalonyl-CoA mutases, ethanolamine ammonia lyase, and diol dehydratase . In mammals, cobalamin is obtained through the diet, and is required for methionine synthase and methylmalonyl-CoA mutase .

This entry represents CobF precorrin-6A synthase (

), a pathway-specific enzyme in the aerobic pathway. After precorrin-4 is methylated at C-11 by CobM to produce precorrin-5, the extruded acyl group is then removed in the subsequent step, which also sees a methyl group added at C-1 in a reaction catalysed by CobF. The product of this reaction is precorrin-6A, which is subsequently reduced by an NADH-dependent reductase to precorrin-6B . This entry identifies CobF in high GC Gram-positive, alphaproteobacteria and pseudomonas-related species.
Cobalamin (vitamin B12) biosynthesis CobG-like (Cbl_synth_CobG-like)
Type: Family

Cobalamin (vitamin B12) is a structurally complex cofactor, consisting of a modified tetrapyrrole with a centrally chelated cobalt. Cobalamin is usually found in one of two biologically active forms: methylcobalamin and adocobalamin. Most prokaryotes, as well as animals, have cobalamin-dependent enzymes, whereas plants and fungi do not appear to use it. In bacteria and archaea, these include methionine synthase, ribonucleotide reductase, glutamate and methylmalonyl-CoA mutases, ethanolamine ammonia lyase, and diol dehydratase . In mammals, cobalamin is obtained through the diet, and is required for methionine synthase and methylmalonyl-CoA mutase .

This entry represents CobG from the aerobic pathway. CobG (precorrin-3b synthase,

,) is a mono-oxygenase containing an iron-sulphur centre. CobG generates a gamma-lactone with the acetate side chain on ring A to give precorrin-3b. An oxygen atom from dioxygen is incorporated into the macrocycle at C-20. In the aerobic cobalamin biosynthesis pathway, four enzymes are involved in the conversion of precorrin-3A to precorrin-6A. The first of the four steps is carried out by CobG, yielding precorrin-3B as the product. This is followed by three methylation reactions, which introduce a methyl group at C-17 (CobJ;

), C-11 (CobM;

) and C-1 (CobF;

) of the macrocycle, giving rise to precorrin-4, precorrin-5 and precorrin-6A, respectively.

This entry also contains ferredoxin-nitrite reductase (

), a key enzyme in the process of nitrogen assimilation that makes use of a sirohaem-iron-sulphur cofactor .
Fatty oxidation complex, alpha subunit FadB (FadB)
Type: Family

Members of this family represent the alpha subunit of the multifunctional enzyme complex of the fatty acid degradation cycle. Activities include: enoyl-CoA hydratase (

), dodecenoyl-CoA delta-isomerase activity (

), 3-hydroxyacyl-CoA dehydrogenase (

) and 3-hydroxybutyryl-CoA epimerase (

). A representative is Escherichia coli FadB (

). This entry excludes the FadJ family represented by

.
Catechol 1,2-dioxygenase, actinobacteria (Cchol_dOase_actb)
Type: Family

Members of this family are catechol 1,2-dioxygenases of the actinobacteria. They are more closely related to actinobacterial chlorocatechol 1,2-dioxygenases than to proteobacterial catechol 1,2-dioxygenases, and so form this separate entry. The member from Rhodococcus rhodochrous is described as a homodimer with bound Fe, similarly active on catechol, 3-methylcatechol and 4-methylcatechol.
Catechol 1,2-dioxygenase, proteobacteria (Cchol_dOase_prob)
Type: Family

Members of this family known so far are catechol 1,2-dioxygenases of the proteobacteria. They are distinct from catechol 1,2-dioxygenases and chlorocatechol 1,2-dioxygenases of the actinobacteria, which are quite similar to each other and resolved by separate entries. This enzyme catalyses intradiol cleavage in which catechol + O2 becomes cis,cis-muconate. Catechol is an intermediate in the catabolism of many different aromatic compounds, as is the alternative intermediate protocatechuate. In Acinetobacter lwoffii, two isozymes are present with abilities, differing somewhat, to act on catechol analogues 3-methylcatechol, 4-methylcatechol, 4-methoxycatechol, and 4-chlorocatechol.
Fatty oxidation complex, alpha subunit FadJ (FadJ)
Type: Family

Members of this family represent the alpha subunit of the multifunctional enzyme complex of the fatty acid degradation cycle, which plays a minor role in aerobic beta-oxidation of fatty acids . The FadJI complex is necessary for anaerobic growth on short-chain acids with nitrate as an electron acceptor. Activities include: enoyl-CoA hydratase (

), 3-hydroxyacyl-CoA dehydrogenase (

), and 3-hydroxybutyryl-CoA epimerase (

). Dehydrogenase activity results in the conversion of NADH to NAD
+
. A representative is the Escherichia coli FadJ protein (also named YfcX) (

). This entry excludes FadB of

.
Fatty acid oxidation complex, alpha subunit, mitochondrial (Fa_ox_alpha_mit)
Type: Family

Members of this family represent the alpha subunit of the mitochondrial multifunctional fatty acid degradation enzyme complex. Subunit activities include: enoyl-CoA hydratase (

) and 3-hydroxyacyl-CoA dehydrogenase (

). Some characterisation of these proteins has been done in human (

), pig (

) and rat (

). The beta subunit has acetyl-CoA C-acyltransferase (

) activity.
Cobaltochelatase subunit, putative (Cob_chelat_sub_put)
Type: Family

Cobaltochelatase is responsible for the insertion of cobalt into the corrin ring of coenzyme B12 during its biosynthesis. Cobalamin (vitamin B12) can be complexed with metal via ATP-dependent reactions (aerobic pathway) (e.g., in Pseudomonas denitrificans) or via ATP-independent reactions (anaerobic pathway) (e.g., in Salmonella typhimurium) . The corresponding cobalt chelatases are not homologous. The two versions have been well described. CbiK/CbiX is a monomeric, anaerobic version which acts early in the biosynthesis (

). CobNST is a trimeric, ATP-dependent, aerobic version which acts late in the biosynthesis (

/

/

). The two pathways differ in the point of cobalt insertion during corrin ring formation . There are apparently a number of variations on these two pathways, where the major differences seem to be concerned with the process of ring contraction .

A number of genomes (actinobacteria, cyanobacteria, betaproteobacteria and pseudomonads) which apparently biosynthesise B12, encode a cobN gene but are demonstrably lacking cobS and cobT. These genomes do, however contain a homologue, represented by this entry, of the magnesium chelatase subunits BchI/BchD family. Aside from the cyanobacteria (which have a separate magnesium chelatase trimer), these species do not make chlorins, so do not have any use for a magnesium chelatase. Furthermore, in nearly all cases the members of this family are proximal to either CobN itself or other genes involved in cobalt transport or B12 biosynthesis.
Acetyl-CoA C-acyltransferase FadA (FadA)
Type: Family

This subunit of the FadBA complex has acetyl-CoA C-acyltransferase (

) activity, and is also known as beta-ketothiolase and fatty oxidation complex, beta subunit. This protein is almost always located adjacent to FadB (

). The FadBA complex is the major complex active for beta-oxidation of fatty acids in Escherichia coli.
Acetyl-CoA C-acyltransferase FadI (Ac-CoA_C-AcTrfase_FadI)
Type: Family

This subunit of the FadJI complex has acetyl-CoA C-acyltransferase (

) activity, and is also known as beta-ketothiolase and fatty oxidation complex, beta subunit, and YfcY. This protein is almost always located adjacent to FadJ (

). The FadJI complex is needed for anaerobic beta-oxidation of short-chain fatty acids in Escherichia coli.
Anti-sigma-E factor ChrR (Anti-sigma_ChrR)
Type: Family

The member of this family from Rhodobacter sphaeroides (Rhodopseudomonas sphaeroides) has been shown both to form a complex with sigma(E) and to negatively regulate tetrapyrrole biosynthesis.

ChrR comprises two structural and functional domains: the N-terminal anti-sigma domain (ASD) binds a Zn(2+) ion, contacts sigma(E), and is sufficient to inhibit sigma(E)-dependent transcription. The ChrR C-terminal domain (CLD) adopts a cupin fold with a conserved PxHxHxGxE motif. It can coordinate an additional Zn(2+), and is required for the transcriptional response to singlet oxygen, a potent oxidant that damages cellular biomolecules and can kill cells .
Conserved hypothetical protein CHP02453 (CHP02453)
Type: Family

Members of this family are widely (though sparsely) distributed bacterial proteins, about 230 residues in length and in fungal proteins, which are around 400 residues in length. All members have a motif RxxRDxRFxxx[DN]KxxY. The function of this protein family is unknown.
Cobalt ECF transporter T component CbiQ (ECF_CbiQ)
Type: Family

This family consists of CbiQ and NikQ. CbiQ is part of the ECF transporter complex CbiMNOQ involved in cobalt import . It can also transport nickel with a very low affinity . NikQ is part of ECF transporter complex NikMNQO involved in nickel import. Similarly, it can also transport cobalt, but with a very low affinity .
Trehalose synthase/alpha-amylase, N-terminal (TreS/a-amylase_N)
Type: Domain

Trehalose synthase interconverts maltose and alpha,alpha-trehalose by transglucosylation. This is one of at least three mechanisms for biosynthesis of trehalose, an important and widespread compatible solute. However, it is not driven by phosphate activation of sugars and its physiological role may tend toward trehalose degradation. This view is accentuated by numerous examples of fusion to a probable maltokinase domain. The sequence region described by this model is found both as the whole of a trehalose synthase and as the N-terminal region of a larger fusion protein that includes trehalose synthase activity. Several of these fused trehalose synthases have a domain homologous to proteins with maltokinase activity from Actinoplanes missouriensis and Streptomyces coelicolor .
Trehalose synthase/probable maltokinase, C-terminal domain (TreS_maltokin_C_dom)
Type: Domain

Three pathways exist for the biosynthesis of trehalose, an osmoprotectant that in some species is also a precursor of certain cell wall glycolipids. Trehalose synthase, TreS, can interconvert maltose and trehalose, but while the equilibrium favours trehalose, physiological concentrations of trehalose may be much greater than that of maltose, and TreS may act largely in its degradation. This entry describes a domain found only as a C-terminal fusion to TreS proteins. The most closely related proteins outside this family, Pep2 of Streptomyces coelicolor and Mak1 of Actinoplanes missouriensis, have known maltokinase activity. We suggest this domain acts as a maltokinase and helps drive conversion of trehalose to maltose.
Mannosyl-3-phosphoglycerate synthase (Osmo_MPG_synth)
Type: Family

This family consists of examples of mannosyl-3-phosphoglycerate synthase (MPGS), which together with mannosyl-3-phosphoglycerate phosphatase (MPGP), comprises a two-step pathway for mannosylglycerate biosynthesis. Mannosylglycerate is a compatible solute that tends to be restricted to extreme thermophiles of archaea and bacteria. Note that in Rhodothermus marinus (Rhodothermus obamensis), this pathway is one of two; the other is condensation of GDP-mannose with D-glycerate by mannosylglycerate synthase.
Pyranose 2-oxidase (P2OX)
Type: Family

Fungal pyranose 2-oxidase (P2OX) catalyses the oxidation of various aldopyranoses and disaccharides on carbon-2 to the corresponding 2-keto sugars concomitant with the reduction of O2 to H2O2. Peroxide production is believed to be important to the wood rot fungi in which this enzyme is found for lignin degradation .
Mannosyl-3-phosphoglycerate phosphatase (MPG_Pase)
Type: Family

Members of this family are mannosyl-3-phosphoglycerate phosphatase (

). It acts sequentially after mannosyl-3-phosphoglycerate synthase (

) in a two-step pathway of biosynthesis of the compatible solute mannosylglycerate, a typical osmolyte of thermophiles .
NADAR (NADAR)
Type: Domain

This entry contains E. coli swarming motility protein YbiA. Mutations in YbiA cause defects in Escherichia coli swarming, but not necessarily in motility. Members of this entry were predicted to be involved in NAD-utilising pathways, likely to act on ADP-ribose derivatives, and were been named NADAR (NAD and ADP-ribose) . More recently, YbiA has been shown to be involved in the disposal of riboflavin intermediates. It catalyses the hydrolysis of the N-glycosidic bond in the first two intermediates of riboflavin biosynthesis, which are highly reactive metabolites, yielding relatively innocuous products . This entry represents the C-terminal domain of Riboflavin biosynthesis protein PYRR from plants, a pyrimidine reductase involved in the riboflavin biosynthesis pathway. It catalyses the hydrolysis of the N-glycosidic bond in the first two intermediates of riboflavin biosynthesis, which are highly reactive metabolites, yielding relatively innocuous products .
Chlorocatechol 1,2-dioxygenase (Chlorcchol_dOase)
Type: Family

Members of this protein family are chlorocatechol 1,2-dioxygenases. This enzyme is a homodimeric intradiol dioxygenase that degrade chlorocatechols via the addition of molecular oxygen and the subsequent cleavage between two adjacent hydroxyl groups. This reaction is part of the modified ortho-cleavage pathway which is a central oxidative bacterial pathway that channels chlorocatechols, derived from the degradation of chlorinated benzoic acids, phenoxyacetic acids, phenols, benzenes, and other aromatics into the energy-generating tricarboxylic acid pathway .

This protein is closely related to catechol 1,2-dioxygenase,

,

. Note: a number of annotated database entries for members of this family have EC numbers that refers to

; whereas members of this family acts in pathways for the biodegradation of chlorinated aromatic compounds.
Precorrin-6Y methyltransferase (CbiE)
Type: Domain

Cobalamin (vitamin B12) is a structurally complex cofactor, consisting of a modified tetrapyrrole with a centrally chelated cobalt. Cobalamin is usually found in one of two biologically active forms: methylcobalamin and adocobalamin. Most prokaryotes, as well as animals, have cobalamin-dependent enzymes, whereas plants and fungi do not appear to use it. In bacteria and archaea, these include methionine synthase, ribonucleotide reductase, glutamate and methylmalonyl-CoA mutases, ethanolamine ammonia lyase, and diol dehydratase . In mammals, cobalamin is obtained through the diet, and is required for methionine synthase and methylmalonyl-CoA mutase .

This entry represents CbiE subunit of precorrin-6Y C5,15-methyltransferase (

) from the anaerobic pathway, a bifunctional enzyme that catalyses two methylations (at C-5 and C-15) in precorrin-6Y, as well as the decarboxylation of the acetate side chain located in ring C, in order to generate precorrin-8X. In the anaerobic pathway, two enzymes are required to produce precorrin-8X: CbiE and CbiT, which can be fused as CbiET (sometimes called CobL) . In the aerobic pathway, the bifunctional enzyme is CobL .
Sucrose-phosphate synthase, plant (SPS_pln)
Type: Family

Sucrose occupies a central position in the metabolic pathways of all plants and plays a variety of roles including transport sugar, storage reserve, compatible solute, and signal compound . This compound is produced by the combined action of two enzymes, sucrose-phosphate synthase (

) and sucrose-phosphate phosphatase (

), via the intermediate sucrose 6-phosphate. Several studies have shown a positive correlation between sucrose-phosphate synthase activity and plant growth rate and yield in agronomically important plants, though direct proof of a causal link is lacking.

This entry represents sucrose-phosphate synthase from plants, which is known to exist in multigene families in several species of both monocots and dicots. The enzyme contains an N-terminal domain glucosyltransferase domain, a variable linker region, and a C-terminal domain similar to that of sucrose-phosphate phosphatase, the next and final enzyme of sucrose biosynthesis. The C-terminal domain is likely to serve a binding - not a catalytic - function, as sucrose-phosphate phosphatase is always encoded by a distinct protein.
Sucrose synthase, plant/cyanobacteria (Sucrose_synthase_pln/cyn)
Type: Family

This entry represents sucrose synthase an enzyme that despite its name, generally uses rather produces sucrose. Sucrose plus UDP (or ADP) becomes D-fructose plus UDP-glucose (or ADP-glucose), which is then available for cell wall (or starch) biosynthesis. The enzyme is homologous to sucrose phosphate synthase, which catalyses the penultimate step in sucrose synthesis. Sucrose synthase is found, so far, exclusively in plants and cyanobacteria .
Sucrose phosphate synthase, sucrose phosphatase-like domain (Sucrose_P_synth_Pase-like_dom)
Type: Domain

Sucrose phosphate synthase (SPS) and sucrose phosphate phosphatase (SPP) are the last two enzymes of sucrose biosynthesis. In cyanobacteria and plants, the C-terminal region of most or all versions of SPS has a domain homologous to the known SPP. This domain may serve a binding or regulatory rather than catalytic function. Sequences in this family are bacterial C-terminal regions found in all but two of the putative bacterial sucrose phosphate synthases described by

.