SII-SWORD/CoKE huggingface dataset:
Purine nucleoside phosphorylase (Purine_phosphorylase)
Type: Family

This entry consists of three clades of purine phosphorylases based on a neighbour-joining tree using the MTAP family as an out group. The highest-branching clade (

) consists of a group of sequences from both Gram-positive and Gram-negative bacteria which have been shown to act as purine nucleotide phosphorylases but whose physiological substrate and role in vivo remain unknown . Of the two remaining clades, one is xanthosine phosphorylase (XAPA,

); it is limited to certain gammaproteobacteria and constitutes a special purine phosphorylase found in a specialised operon for xanthosine catabolism . The enzyme also acts on the same purines (inosine and guanosine) as the other characterised members of this subfamily, but is only induced when xanthosine must be degraded. The remaining and largest clade consists of purine nucleotide phosphorylases (PNPH,

) from metazoa and bacteria which act primarily on guanosine and inosine, and do not act on adenosine. Sequences from Clostridium and Thermotoga fall between these last two clades and are uncharacterised with respect to substrate range.
Putative purine nucleotide phosphorylase (PUNP)
Type: Family

This entry describes purine nucleotide phosphorylases (PNPs). Some proteins in this entry have been shown to act on inosine and guanosine, though their physiological substrates and role in vivo are not known . Closely related clades act on inosine and guanosine (PNPH,

), and xanthosine, inosine and guanosine (XAPA,

) neither of these will act on adenosine. A more distantly related clade (MTAP,

) acts on methylthioadenosine.

The structure of the Cellulomonas enzyme (

) has been determined . This enzyme is a homotrimer where the subunits appear to bind cooperatively and trimerisation occurs through both hydrogen bonding and hydrophobic interactions. The core of each subunit, like other trimeric PNPs, consists of a nine-stranded β sheet, though the surrounding helices are less well conserved. The postions and geometric arrangments of the three active sites of each trimer are also conserved with other trimeric PNPs.
Purine nucleoside phosphorylase I, inosine/guanosine-specific (Pur_Nuc_Pase_Ino/Guo-sp)
Type: Family

This entry represents a family of bacterial and metazoan purine phosphorylases acting primarily on inosine and guanosine and not acting on adenosine. PNP-I refers to the nomenclature from Bacillus stearothermophilus (Geobacillus stearothermophilus) where PHP-II refers to the nucleotidase acting on adenosine as the primary substrate. The bacterial enzymes (PUNA) are typified by the Bacillus PupG protein which is involved in the metabolism of nucleosides as a carbon source. Several metazoan enzymes (PNPH) are well characterised including the human and bovine enzymes which have been crystallised.
AMP nucleosidase (AMP_nucleosidase)
Type: Family

AMP nucleosidase (AMN) catalyses the hydrolysis of AMP to form adenine and ribose 5-phosphate. It is only found in prokaryotes, where it plays a role in purine nucleoside salvage and intracellular AMP level regulation . The gene for AMP nucleosidase from Escherichia coli (amn) encodes a protein of 483 amino acids. A comparison of the amino acid sequence for AMP nucleosidase with that for yeast AMP deaminase shows that there is a region where only six out of eight amino acids are identical but there is no other overall homology. AMN also showed little similarity to consensus sequences for adenylate binding sites even though the enzyme is known to have a catalytic site for AMP and regulatory sites for MgATP and phosphate .
Lactate dehydrogenase, protist (Lactate_DH_protist)
Type: Family

This entry represents a family of protist (Trichomonad) lactate dehydrogenases which have apparently evolved from a recent protist malate dehydrogenase ancestor . Lactate dehydrogenase converts the hydroxyl at C-2 of lactate to a carbonyl in the product, pyruvate. The preference of this enzyme for NAD or NADP has not been determined. A critical residue in malate dehydrogenase, arginine-91 (Trichomonas vaginalis numbering) has been mutated to a leucine, eliminating the positive charge which complemented the carboxylate in malate which is absent in lactate. Several other more subtle changes are proposed to make the active site smaller to accommodate the less bulky lactate molecule .
Malate dehydrogenase, NADP-dependent, plants (Malate_DH_NADP-dep_pln)
Type: Family

This entry represents the NADP-dependent malate dehydrogenase found in plants, mosses and green algae and localised to the chloroplast. Malate dehydrogenase converts oxaloacetate into malate, a critical step in the C4 cycle which allows circumvention of the effects of photorespiration. Malate is subsequently transported from the chloroplast to the cytoplasm (and then to the bundle sheath cells in C4 plants). The plant and moss enzymes are light regulated via cysteine diisulphide bonds. The enzyme from sorghum has been crystallised .
Malate dehydrogenase, NAD-dependent, cytosolic (Malate_DH_NAD-dep_euk)
Type: Family

Malate dehydrogenase (MDH) is one of the key enzymes in the citric acid cycle, facilitating both the conversion of malate to oxaloacetate and replenishing levels of oxalacetate by reductive carboxylation of pyruvate . There are several isoforms of MDH, differing in their subcellular localization and their specificity for the cofactor NAD or NADP . Members of this family are eukaryotic NAD-dependent MDHs localized to the cytoplasm and cytosol.

The enzyme from pig has been studied by X-ray crystallography .
Malate dehydrogenase, type 3 (Malate_DH_type3)
Type: Family

This entry contains bacterial and archaeal malate dehydrogenases, which convert malate into oxaloacetate in the citric acid cycle. The critical residues which discriminate malate dehydrogenase from lactate dehydrogenase have been characterised , and have been used to determine members of this group.
TonB-dependent haem/haemoglobin receptor (TonB_haem/Hb_rcpt)
Type: Family

This entry represents the TonB-dependent outer membrane haem/haemoglobin receptor/transporter found in bacteria which live in contact with animals (which contain haemoglobin or other haem-bearing globins) or legumes (which contain leghaemoglobin). Some species such as Nostoc, Caulobacter and Chlorobium do not have an obvious source of haemoglobin-like proteins in their biological niche and so the possibility exists that they act on some other substance.

The haem transport system from haem-haemopexin from Haemophilus influenzae consists of HxuC, a haem receptor, and the two-partner-secretion system HxuB/HxuA. HxuB and HxuA are required only for utilization of haem from haem-haemopexin complexe. HxuA forms complexes with haem-haemopexin, leading to haem release and its capture by TonB-dependent receptor HxuC. HxuC likely functions as an outer-membrane haem-binding protein and/or transmembrane transport protein .
Chorismate mutase, T-protein (CM_T)
Type: Domain

This entry represents the chorismate mutase domain of the gamma proteobacterial 'T-protein' which consists of an N-terminal chorismate mutase domain and a C-terminal prephenate dehydrogenase domain.
2-methylcitrate synthase/citrate synthase type I (2-MeCitrate/Citrate_synth_II)
Type: Family

Members of this family are dimeric enzymes with activity as 2-methylcitrate synthase, citrate synthase, or both. Many Gram-negative species have a hexameric citrate synthase, termed citrate synthase I. Members of this family appear as a second citrate synthase isozyme, but typically are associated with propionate metabolism and synthesise 2-methylcitrate from propionyl-CoA; citrate synthase activity may be incidental . A number of species, including Thermoplasma acidophilum, Pyrococcus furiosus, and the Antarctic bacterium DS2-3R have a bifunctional member of this family as the only citrate synthase isozyme.
Chorismate mutase, Gram-positive (Chorismate_mutase_GmP)
Type: Domain

This entry represents a clade of chorismate mutase proteins/domains from Gram-positive species. The sequence from Enterococcus is fused to the C terminus of an apparent acetyltransferase, and the sequence from Clostridium acetobutylicum (but not perfringens) is fused to the N terminus of shikimate-5-dehydrogenase, another enzyme of the chorismate pathway. All the other members of this clade are mono-functional. Members of this clade from Streptococcus and Lactococcus have been found which represent the sole chorismate mutase domain in their respective genomes which also exhibit evidence of the enzymes of both the upstream and downstream branches of the chorismate pathways.
Succinate dehydrogenase/fumarate reductase flavoprotein subunit, low-GC Gram-positive bacteria (Succ_DH/Fum_Rdt_flav_su)
Type: Family

This entry represents the succinate dehydrogenase flavoprotein subunit as found in the low-GC Gram-positive bacteria and a few other lineages. This enzyme may act in a complete or partial TCA cycle, or act in the opposite direction as fumarate reductase. In some but not all species, succinate dehydrogenase and fumarate reductase may be encoded as separate isozymes. This entry also includes Adenylylsulfate reductase subunit alpha which shares a common evolutionary origin with fumarate reductase/succinate dehydrogenase flavoproteins .
Succinate dehydrogenase, flavoprotein subunit (Succ_DH_flav_su_fwd)
Type: Family

Succinate dehydrogenase and fumarate reductase are homologous enzymes reversible in principle but favoured under different circumstances. This entry represents a narrowly defined clade of the succinate dehydrogenase flavoprotein subunit as found in mitochondria, in Rickettsia, in Escherichia coli and other proteobacteria, and in a few other lineages. However, excluded are all known fumarate reductases. It also excludes putative succinate dehydrogenases that appear to diverged before the split between E. coli succinate dehydrogenase and fumarate reductase.
2-amino-3-ketobutyrate coenzyme A ligase (2am3keto_CoA_ligase)
Type: Family

2-amino-3-ketobutyrate coenzyme A ligase (KBL), also called glycine C-acetyltransferase, is a pyridoxal phosphate (PLP) dependent enzyme that catalyses the cleavage of 2-amino-3-ketobutyrate to glycine and acetyl-CoA, the second step in the conversion of L-threonine to glycine in both prokaryotes and eukaryotes .
Acetoacetyl-CoA reductase (Acetoacetyl-CoA_reductase)
Type: Family

This entry represent acetoacetyl-CoA reductase, a member of the family short-chain-alcohol dehydrogenases. Note that, despite the precision implied by the enzyme name, the reaction of

is defined more generally as (R)-3-hydroxyacyl-CoA + NADP+ = 3-oxoacyl-CoA + NADPH. Members of this family may act in the biosynthesis of poly-beta-hydroxybutyrate (e.g. Rhizobium meliloti (Sinorhizobium meliloti)) and related poly-beta-hydroxyalkanoates. Note that the member of this family from Azospirillum brasilense, designated NodG, appears to lack acetoacetyl-CoA reductase activity and to act instead in the production of nodulation factor.
3-oxoacyl-(acyl-carrier-protein) reductase (3oxo_ACP_reduc)
Type: Family

This entry represents 3-oxoacyl-[ACP] reductase, also called 3-ketoacyl-acyl carrier protein reductase, an enzyme of fatty acid biosynthesis found in many plant and bacterial species. This enzyme is involved in type II fatty acid biosynthesis, where the individual metabolic transformations are carried out by different enzymes rather than by a single enzyme as occurs in type I fatty acid biosynthesis . This family includes Sinorhizobium meliloti NodG, which has been shown to be a 3-oxoacyl-ACP reductase and can play a role in fatty acid synthesis .

Structural studies show that the enzyme is a tetramer which forms a typical Rossman fold . Unlike other members of the short-chain dehydrogenase/reductase superfamily, the enzyme undergoes a marked conformational change upon binding of the NADP(H)cofactor. This conformational change aligns the side chains of the catalytic triad at the active site in an active conformation and increases the affinity of the enzyme for its substrate.
3-oxoacyl-(acyl-carrier-protein) reductase, putative (FabG-rel)
Type: Family

This entry represents a small, very well conserved family of proteins closely related to the FabG family,

, and possibly equal in function. In all completed genomes with a member of this family, a FabG in

is also found.
2-dehydro-3-deoxy-D-gluconate 5-dehydrogenase (2-deoxy-D-gluc_3_DH)
Type: Family

This entry describes 2-dehydro-3-deoxy-D-gluconate 5-dehydrogenase (also called 2-keto-3-deoxygluconate oxidoreductase), a member of the family of short-chain-alcohol dehydrogenases. This protein from Erwinia chrysanthemi has been characterised as an enzyme of pectin degradation .
Poly(R)-hydroxyalkanoic acid synthase, class II (PHA_synth_II)
Type: Family

This entry represents the class II subfamily of poly(R)-hydroxyalkanoate synthases, which polymerises hydroxyacyl-CoAs, typically with six to fourteen carbons in the hydroxyacyl backbone into aliphatic esters termed poly(R)-hydroxyalkanoic acids . These polymers accumulate as carbon and energy storage inclusions in many species and can amount to 90 percent of the dry weight of cell.
D-tagatose-bisphosphate aldolase, class II, subunit KbaY/GatY (TagBP_ald_KbaY/GatY)
Type: Family

Escherichia coli and other enteric bacteria contain two closely related D-tagatose 1,6-bisphosphate (TagBP)-specific aldolases - KbaYZ (also known as AgaYZ) and GatYZ. Unlike other class II aldolases, which are homodimeric enzymes, KbaYZ and GatYZ are heterodimers, and are comprised of subunits KbaY/GatY and GatY/GatZ.

The KbaY/GatY subunits alone are sufficient to show aldolase activity and contain most or all of the residues that have been identified as essential for substrate/product recognition and catalysis in class II aldolases . However, subunits GatZ/KbaZ are required for full activity and for good in vivo and in vitro stability.

This entry represents D-tagatose-1,6-bisphosphate aldolase catalytic subunits KbaY and GatY.
Fructose-1,6-bisphosphate aldolase, class 2 (Fruc_bis_ald_class-2)
Type: Family

Fructose-1,6-bisphosphate (FBP) aldolases reversibly cleave FBP to two triose phosphates, glycerone phophate and D-glyceraldehyde 3-phosphate. They play a key role in both glycolysis (FBP cleavage) and gluconeogenesis (FBP synthesis). These enzymes can be divide into two classes based on their mode of catalysis. Class I FBP aldolases form a Schiff-base intermediate between glycerone phophate and an active site lysine residue, while the class II enzymes use a divalent cation such as Zn(2+) for catalysis .

This entry represents class II FBP aldolases found in Gram-positive bacteria, a variety of Gram-negative baceria, and amitochondriate protists. These enzymes are homotetramers where each momomer forms a TIM barrel fold .
Nitrogenase iron-iron protein, alpha chain (Nase_Fe-Fe_asu)
Type: Family

This entry represents the all-iron variant of the nitrogenase component I alpha chain. Molybdenum-iron and vanadium iron forms are also found. The complete complex contains two alpha chains, two beta chains and two delta chains. The component I associates with component II also known as the iron protein which serves to provide electrons for component I.
Peptidase M20A, peptidase V (Pept_M20A_peptidaseV)
Type: Family

This entry represents a small clade of dipeptidase enzymes from the Lactobacillaceae, which belong to MEROPS peptidase family M20A. The Lactococcus lactis enzyme has been shown to act on a wide range of dipeptides, but not larger peptides . The enzyme from Lactobacillus delbrueckii was originally characterised as a Xaa-His dipeptidase, specifically a carnosinase (beta-Ala-His) by complementation of an Escherichia coli mutant. Further study, including the crystallisation of the enzyme, has shown it to also be a non-specific dipeptidase . This group also includes enzymes from Streptococcus and Enterococcus.
Na(+)-translocating NADH-quinone reductase subunit D (NqrD)
Type: Family

Na(+)-translocating NADH-quinone reductase (NQR) functions as a primary Na(+) pump in the respiratory chain of Gram-negative marine and halophilic bacteria . The NQR complex reduces ubiquinone-1 to ubiquinol by two successive reactions, which involve the co-factor FAD. The NQR complex is composed of six subunits, this entry representing subunit D (NqrD).
Ion-translocating oxidoreductase complex, subunit RnfA/RsxA (Ion_transpt_RnfA/RsxA)
Type: Family

The six subunit complex RnfABCDGE in Rhodobacter capsulatus (Rhodopseudomonas capsulata) encodes an apparent NADH oxidoreductase responsible for electron transport to nitrogenase, necessary for nitrogen fixation . A closely related complex in Escherichia coli, RsxABCDGE (Reducer of SoxR), reduces the 2Fe-2S-containing superoxide sensor SoxR, active as a transcription factor when oxidized . This family of putative NADH oxidoreductase complexes exists in many of the same species as the related NQR, a Na(+)-translocating NADH-quinone reductase, but is distinct. This entry describes the A subunit.
3-hydroxybutyrate dehydrogenase (3-OHbutyrate_DH)
Type: Family

This entry represents a subfamily of the short chain dehydrogenases. Characterised members so far as 3-hydroxybutyrate dehydrogenases and are found in species that accumulate ester polymers called polyhydroxyalkanoic acids (PHAs) under certain conditions. Several members of the family are from species not known to accumulate PHAs, including Oceanobacillus iheyensis and Bacillus subtilis. However, polymer formation is not required for there be a role for 3-hydroxybutyrate dehydrogenase; it may be members of this family have the same function in those species.
2-polyprenyl-6-methoxyphenol 4-hydroxylase (UbiH)
Type: Family

This entry represents the FAD-dependent monooxygenase responsible for the second hydroxylation step in the aerobic ubiquinone biosynthetic pathway . The sequences in this entry are restricted to the proteobacteria. This family is closely related to the UbiF hydroxylase which catalyses the final hydroxylation step. The enzyme has also been named VisB due to a mutant visible light sensitive phenotype.
Phosphotransferase system, trehalose-specific IIBC component (PTS_IIBC_treh)
Type: Domain

This entry represents the fused enzyme II B and C components of the trehalose-specific PTS sugar transporter system . Trehalose is converted to trehalose-6-phosphate in the process of translocation into the cell. These transporters lack their own IIA domains and instead use the glucose IIA protein (IIAglc or Crr) . The exceptions to this rule are Staphylococci and Streptococci which contain their own A domain as a C-terminal fusion. This family is closely related to the sucrose transporting PTS IIBC enzymes described by the IIB component and the IIC component (

), respectively. In Escherichia coli, Bacillus subtilis and Pseudomonas fluorescens the presence of this gene is associated with the presence of trehalase which degrades T6P to glucose and glucose-6-P. Trehalose may also be transported (in Salmonella) via the mannose PTS or galactose permease systems , or (in Sinorhizobium, Thermococcus and Sulfolobus, for instance) by ABC transporters .
Phosphotransferase system, beta-glucoside-specific IIABC component (PTS_IIABC_b_glu)
Type: Family

The phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS) is a major carbohydrate transport system in bacteria. The PTS catalyses the phosphorylation of incoming sugar substrates and coupled with translocation across the cell membrane, makes the PTS a link between the uptake and metabolism of sugars.

The general mechanism of the PTS is the following: a phosphoryl group from phosphoenolpyruvate (PEP) is transferred via a signal transduction pathway, to enzyme I (EI) which in turn transfers it to a phosphoryl carrier, the histidine protein (HPr). Phospho-HPr then transfers the phosphoryl group to a sugar-specific permease, a membrane-bound complex known as enzyme 2 (EII), which transports the sugar to the cell. EII consists of at least three structurally distinct domains IIA, IIB and IIC . These can either be fused together in a single polypeptide chain or exist as two or three interactive chains, formerly called enzymes II (EII) and III (EIII).

This entry represents a family of PTS enzyme II proteins in which all three domains are found in the same polypeptide chain and which appear to have a broad specificity for beta-glucosides including salicin (beta-D-glucose-1-salicylate) and arbutin (hydroquinone-O-beta-D-glucopyranoside) . These are distinct from the closely related sucrose-specific and trehalose-specific PTS transporters.
PTS system glucose-specific IIBC component (PTS_IIBC_glc)
Type: Domain

This entry represents the combined B and C domains of the PTS transport system enzyme II specific for glucose transport . Many of the genes in this family also include an A domain as part of the same polypeptide and thus should be given the name 'PTS system, glucose-specific IIABC component' while the Bacillus subtilus enzyme also contains an enzyme III domain which appears to act independently of the enzyme II domains . This group is most closely related to the N-acetylglucosamine-specific PTS enzymes (

).
Phosphotransferase system, IIBC component (PTS_IIBC)
Type: Domain

This entry represents a group of fused B and C components of PTS enzyme II. This clade is a member of a larger family which contains enzyme II's specific for a variety of sugars including glucose (

) and N-acetylglucosamine (

). None of the members of this clade have been experimentally characterised. This clade includes sequences from Streptococcus and Enterococcus which also include a C-terminal A domain as well as Bacillus and Clostridium which do not. In nearly all cases, these species also contain an authentic glucose-specific PTS transporter.
PTS system, maltose/glucose-specific IIBC component (PTS_Mal/Glc-sp_IIBC_component)
Type: Family

This entry represents a family of PTS enzyme II fused B and C components including and most closely related to the MalX maltose and glucose-specific transporter of Escherichia coli .
Ion-translocating oxidoreductase complex subunit RnfD, bacterial (RnfD_bac)
Type: Family

This entry describes the D subunit.

The six-subunit complex RnfABCDGE in Rhodobacter capsulatus (Rhodopseudomonas capsulata) encodes a NADH oxidoreductase responsible for electron transport to nitrogenase, necessary for nitrogen fixation . A closely related complex in Escherichia coli, RsxABCDGE (Reducer of SoxR), reduces the 2Fe-2S-containing superoxide sensor SoxR, active as a transcription factor when oxidized . The Rnf complex is ferredoxin:NAD+ oxidoreductase that appears to pump different ions in different bacteria. In Clostridium ljungdahlii and Desulfovibrio alaskensis functions as a proton pump whose activity is important for growth , whereas in Acetobacterium woodii functions as a Na(+)-translocating electron transport chain .
L-lactate dehydrogenase (L-lactate_DH)
Type: Family

This entry represents the NAD-dependent L-lactate dehydrogenases from bacteria and eukaryotes. This enzyme functions as the final step in anaerobic glycolysis. Although lactate dehydrogenases have in some cases been mistaken for malate dehydrogenases due to the similarity of these two substrates and the apparent ease with which evolution can toggle these activities, critical residues have been identified which can discriminate between the two activities.