SII-SWORD/CoKE huggingface dataset:
Putative pyrophosphorylase ModD (ModD)
Type: Family

ModD is found with molybdenum transport genes modABC in Rhodobacter capsulatus. However, disruption of modD causes only a 4-fold (rather than 500-fold for modA, modB, modC) change in the external molybdenum concentration required to suppress an alternative nitrogenase . ModD proteins are highly similar to nicotinate-nucleotide pyrophosphorylase (also called quinolinate phosphoribosyltransferase). Their function is unknown.
Photosystem I PsaA (PSI_PsaA)
Type: Family

Photosystem I is a membrane complex found in the chloroplasts of plants and cyanobacteria. It uses light energy to transfer electrons from plastocyanin to ferredoxin .
The core proteins of photosystem I are PsaA and PsaB, homologous integral membrane proteins that form a heterodimer that binds the electron-donating chlorophyll dimer P700, as well as chlorophyll, phylloquinone, and 4FE-4S electron acceptors .

This entry represents PsaA.
Photosystem I PsaB (PSI_PsaB)
Type: Family

Photosystem I is a membrane complex found in the chloroplasts of plants and cyanobacteria. It uses light energy to transfer electrons from plastocyanin to ferredoxin .
The core proteins of photosystem I are PsaA and PsaB, homologous integral membrane proteins that form a heterodimer that binds the electron-donating chlorophyll dimer P700, as well as chlorophyll, phylloquinone, and 4FE-4S electron acceptors .

This entry represents PsaB.
Allophycocyanin, beta subunit (Allophycocyanin_b)
Type: Family

This family of sequences represents the allophycocyanin beta subunit. The alpha and beta subunits of allophycocyanin form heterodimers, six of which associate into larger aggregates as part of the phycobilisome, a light-harvesting complex of phycobiliproteins and linker proteins . Other homologous phyobiliproteins include allophycocyanin alpha chain, and the phycocyanin and phycoerythrin alpha and beta chains.
Phycocyanin, alpha subunit (Phycocyanin_a)
Type: Family

This family represent the phycocyanin alpha subunit. Homologous phyobiliproteins of the phycobilisome include phycocyanin alpha chain and the allophycocyanin and phycoerythrin alpha and beta chains. Not included are the closely related phycoerythrocyanin alpha subunit sequences.

Phycocyanin is the major phycobiliprotein in the phycobilisome (PBS) rod, including the light-harvesting photosynthetic bile pigment-protein and the tetrapyrrole chromophore-protein from the phycobiliprotein complex .
Phycocyanin, beta subunit (Phycocyanin_b)
Type: Family

These sequences describe the phycocyanin beta subunit. Other, homologous phycobiliproteins of the phycobilisome include phycocyanin beta chain and the allophycocyanin and phycoerythrin alpha and beta chains. Not included are the closely related phycoerythrocyanin beta subunit sequences.
Homoaconitase/3-isopropylmalate dehydratase, large subunit (Homoacnase/IPMdehydase_lsu)
Type: Family

3-isopropylmalate dehydratase (or isopropylmalate isomerase;

) catalyses the stereo-specific isomerisation of 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate. This enzyme performs the second step in the biosynthesis of leucine, and is present in most prokaryotes and many fungal species. The prokaryotic enzyme is a heterodimer composed of a large (LeuC) and small (LeuD) subunit, while the fungal form is a monomeric enzyme. Both forms of isopropylmalate are related and are part of the larger aconitase family . Aconitases are mostly monomeric proteins which share four domains in common and contain a single, labile [4Fe-4S] cluster. Three structural domains (1, 2 and 3) are tightly packed around the iron-sulphur cluster, while a fourth domain (4) forms a deep active-site cleft. The prokaryotic enzyme is encoded by two adjacent genes, leuC and leuD, corresponding to aconitase domains 1-3 and 4 respectively . LeuC does not bind an iron-sulphur cluster. It is thought that some prokaryotic isopropylamalate dehydrogenases can also function as homoaconitase

, converting cis-homoaconitate to homoisocitric acid in lysine biosynthesis . Homoaconitase has been identified in higher fungi (mitochondria) and several archaea and one thermophilic species of bacteria, Thermus thermophilus . It is also found in the higher plant Arabidopsis thaliana, where it is targeted to the chloroplast .

This entry represents the large subunit of 3-isopropylmalate dehydratase (LeuC), as well as homoaconitase, certain aconitases and uncharacterised proteins. Homoaconitase, aconitase and 3-isopropylmalate dehydratase have similar overall structures and domain organisation . All are dehydratases that bind a [4Fe-4S]-cluster. The majority of the members of this family have been designated as 3-isopropylmalate dehydratase large subunit (LeuC) in microbial genome annotation, but the only characterised member is Thermus thermophilus homoaconitase, an enzyme of a non-aspartate pathway of lysine biosynthesis.
Malate synthase A (Malate_synthA)
Type: Family

This entry represents glyoxysomal malate synthases and one of two bacterial forms, designated malate synthase A.

Malate synthase and isocitrate lyase are the two characteristic enzymes of the glyoxylate cycle. The glyoxylate cycle allows certain organisms, like plants and fungi, to derive their carbon requirements from two-carbon compounds, by bypassing the two carboxylation steps of the citric acid cycle . Isocitrate lyase, first catalyzes the aldol cleavage of isocitrate to succinate (an intermediate of the tricarboxylic acid cycle) and glyoxylate. Then malate synthase catalyzes the condensation of acetyl CoA with glyoxylate to yield malate (another intermediate of the tricarboxylic acid cycle) .
Malate synthase G (Malate_synthG)
Type: Family

Malate synthase G (MSG, 723 residues) is an enzyme of the glyoxylate pathway, that catalyses the Claisen condensation and subsequent hydrolysis of acetyl-coenzyme A (acetyl-CoA) and glyoxylate to form malate and CoA . This biochemical bypass is used by microorganisms (bacteria, yeast, and fungi) for biosynthesis under anaerobic conditions . Enzymes of the glyoxylate bypass have been implicated as virulence factors in several pathogens, including Mycobacterium tuberculosis .

The X-ray structure of the ternary abortive complex of MSG with pyruvate (glyoxylate mimic) and acetyl-CoA has been determined and shown to have the same structure as in the complex with glyoxylate . MSG is composed of four domains: an N-terminal α-helical clasp, a central TIM barrel α/β core, an α/β domain which may have a regulatory function, and a C-terminal five α-helical bundle . The cleft between the TIM β/α-barrel fold and the C-terminal helical domain forms the active site of malate synthases .
Isocitrate lyase (Isocitrate_lyase)
Type: Family

Isocitrate lyase (

) is an enzyme that catalyzes the conversion of isocitrate to succinate and glyoxylate. This is the first step in the glyoxylate bypass, an alternative to the tricarboxylic acid cycle (also known as the TCA cycle) in bacteria, fungi and plants. A cysteine, a histidine and a glutamate or aspartate have been found to be important for the enzyme's catalytic activity. Only one cysteine residue is conserved between the sequences of the fungal, plant and bacterial enzymes; it is located in the middle of a conserved hexapeptide.

Mitochondrial 2-methylisocitrate lyase ICL2 from the yeast Saccharomyces cerevisiae does not act on isocitrate but on 2-methylisocitrate. It catalyses the formation of pyruvate and succinate during the metabolism of endogenous propionyl-CoA . Methylisocitrate lyase, mitochondrial from the filamentous fungus Aspergillus nidulans is responsible for the same reaction .
Dihydrolipoamide succinyltransferase (SucB)
Type: Family

These sequences describe the TCA cycle 2-oxoglutarate system E2 component, dihydrolipoamide succinyltransferase. It is closely related to the pyruvate dehydrogenase E2 component, dihydrolipoamide acetyltransferase. Members include the mitochondrial and Gram-negative bacterial forms. Mycobacterial candidates are highly derived, differ in having and extra copy of the lipoyl-binding domain at the N terminus and are generally excluded from this group of sequences as are all examples of dihydrolipoamide acetyltransferase.
Dihydrolipoamide acetyltransferase pyruvate dehydrogenase complex (AcTrfase_Pyrv_DH_cplx)
Type: Family

This group of sequences are a subset of pyruvate dehydrogenase complex dihydrolipoamide acetyltransferase specifically close by both phylogenetic and percent identity (UPGMA) trees. Members contain two or three copies of the lipoyl-binding domain. Escherichia coli AceF is included in this set while mitochondrial and some other bacterial forms are excluded.
Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex (LAT1)
Type: Family

The pyruvate dehydrogenase complex catalyses the overall conversion of pyruvate to acetyl-CoA and CO2. It contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3) . This entry represent the dihydrolipoamide acetyltransferase (E2) subunit (

), also known as Lat1.
Dihydrolipoamide dehydrogenase (Lipoamide_DH)
Type: Family

These sequences represent dihydrolipoamide dehydrogenase, a flavoprotein that acts in a number of ways. It is the E3 component of dehydrogenase complexes for pyruvate, 2-oxoglutarate, 2-oxoisovalerate, and acetoin. It can also serve as the L protein of the glycine cleavage system. This family includes a few members known to have distinct functions (ferric leghemoglobin reductase and NADH:ferredoxin oxidoreductase) but that may be predicted by homology to act as dihydrolipoamide dehydrogenase as well. The motif GGXCXXXGCXP near the N terminus contains a redox-active disulphide.
Adenylate kinase subfamily (Adenyl_kin_sub)
Type: Family

Adenylate kinase (

) converts ATP + AMP to ADP + ADP, that is, it uses ATP as a phosphate donor for AMP. Most members of this family are known or believed to be adenylate kinase. However, some members accept other nucleotide triphosphates as donors, may be unable to use ATP, and may fail to complement adenylate kinase mutants. An example of a nucleoside-triphosphate--adenylate kinase (

) is

, a GTP:AMP phosphotransferase.
TonB/TolA, C-terminal (TonB/TolA_C)
Type: Domain

TonB is bound to an inner membrane-bound protein ExbB via a globular domain and has a flexible middle region that is likely to help in positioning the C-terminal domain into the iron-transporter barrel in the outer membrane .

This entry represents the C-terminal domain of TonB. TonB_C interacts with the N-terminal TonB box of the outer membrane transporter that binds the Fe3+-siderophore complex. The barrel of the transporter, consisting of 22 β-sheets and an inside plug, binds the iron complex in the barrel entrance .
dGTP triphosphohydrolase (dGTPase)
Type: Family

This entry represents a group of dNTP triphosphohydrolases, which is an class of enzymes capable of hydrolysing deoxynucleoside 5'-triphosphates (dNTPs) into the corresponding deoxynucleosides and tripolyphosphate (PPPi) . They can be classified into three subgroups :

Type 1: represented by E. coli dGTPase and

, which preferentially hydrolyzes dGTP without an activator .

Type 2: represented by

, which hydrolyses multiple kinds of dNTP upon activation by binding of an activator .

Type 3: represented by

, which hydrolyses multiple kinds of dNTP without an activator .
Cytidine deaminase, homotetrameric (Cyt_deam_tetra)
Type: Family

This family represents the small homotetrameric form cytidine deaminase, which is a zinc metalloprotein. It is found in humans and most bacteria. A related homodimeric form,

, with a much larger subunit is found in Escherichia coli and in Arabidopsis thaliana (Mouse-ear cress). Both types may act on deoxycytidine as well as cytidine .
Cytidine deaminase, homodimeric (Cyt_deam_dimer)
Type: Family

This family represents the homodimeric form of cytidine deaminase, a zinc metalloprotein found in Escherichia coli and in Arabidopsis thaliana (Mouse-ear cress). A related, homotetrameric form with a much smaller subunit is found most bacteria and in animals,

. Both types may act on deoxycytidine as well as cytidine.
3-phosphoshikimate 1-carboxyvinyltransferase (EPSP_synthase)
Type: Family

This entry represents 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase (also known as 3-phosphoshikimate 1-carboxyvinyltransferase), catalyses the sixth step in the biosynthesis from chorismate of the aromatic amino acids (the shikimate pathway) in bacteria (gene aroA), plants and fungi (where it is part of a multifunctional enzyme which catalyses five consecutive steps in this pathway) . The sixth step is the formation of EPSP and inorganic phosphate from shikimate-3-phosphate (S3P) and phosphoenolpyruvate (PEP).

EPSP can use shikimate or shikimate-3-phosphate as a substrate. By binding shikimate, the backbone of the active site is changed, which affects the binding of glyphosate and renders the reaction insensitive to inhibition by glyphosate . On isolation of the discontinuous C-terminal domain, it was found that it binds neither its substrate nor its inhibitor but maintains structural integrity .

Earlier studies suggested that the active site of the enzyme is in the cleft between its two globular domains. When the enzyme binds S3P, there is a conformational change in the isolated N-terminal domain . The sequence of EPSP from various biological sources shows that the structure of the enzyme has been well conserved throughout evolution. Two strongly conserved regions are well defined. The first one corresponds to a region that is part of the active site and which is also important for the resistance to glyphosate . The second second one is located in the C-terminal part of the protein and contains a conserved lysine which seems to be important for the activity of the enzyme.

Since the shikimate pathway is not present in vertebrates but is essential for the life of plants, fungi and bacteria, it is commonly viewed as a target for antimicrobial drug development.
UMP-CMP kinase (UMP_CMP_kinase)
Type: Family

This entry represents the UMP-CMP kinase subfamily of the adenylate kinase family. UMP-CMP kinase catalyses the phosphorylation of pyrimidine nucleoside monophosphates at the expense of ATP and is involved in de novo pyrimidine nucleotide biosynthesis . In budding yeast, it is also known as Ura6 .
Adenylate kinase, isozyme 1/5 (AK1/5)
Type: Family

Adenylate kinases (AKs) are nucleoside monophosphate kinases, which catalyse the phosphorylation of AMP by using ATP or GTP as phosphate donors.
Phospho-2-dehydro-3-deoxyheptonate aldolase, subtype 2 (DAHP_syn_2)
Type: Domain

This entry describes one of at least three types of phospho-2-dehydro-3-deoxyheptonate aldolase (DAHP synthase). This enzyme catalyzes the first of 7 steps in the biosynthesis of chorismate, that last common precursor of all three aromatic amino acids and of PABA, ubiquinone and menaquinone. Some members of this family, including an experimentally characterised member from Bacillus subtilis, are bifunctional, with a chorismate mutase domain N-terminal to this region. The member of this family from Synechocystis PCC 6803, CcmA, was shown to be essential for carboxysome formation. However, no other candidate for this enzyme is present in that species, chorismate biosynthesis does occur, other species having this protein lack carboxysomes but appear to make chorismate, and a requirement of CcmA for carboxysome formation does not prohibit a role in chorismate biosynthesis.
3-deoxy-8-phosphooctulonate synthase (KDO8P_synthase)
Type: Family

These sequences describe 2-dehydro-3-deoxyphosphooctonate aldolase. Alternate names include 3-deoxy-d-manno-octulosonic acid 8-phosphate and KDO-8 phosphate synthetase. It catalyzes the aldol condensation of phosphoenolpyruvate with D-arabinose 5-phosphate.

phosphoenolpyruvate + D-arabinose 5-phosphate + H
2
O = 2-dehydro-3-deoxy-D-octonate 8-phosphate + phosphate

In Gram-negative bacteria, this is the first step in the biosynthesis of 3-deoxy-D-manno-octulosonate, part of the oligosaccharide core of lipopolysaccharide.
Streptococcal histidine triad repeat (Strep_his_triad_rpt)
Type: Repeat

This entry represents a repeated sequence region that includes a His-X-X-His-X-His (histidine triad) motif, which is found in a family of predominantly streptococcal proteins. Members of the family are suggested to cleave human complement component 3, and family member PhpA has been shown in vaccine studies to be a protective antigen in mice .
Phosphoserine aminotransferase, Methanosarcina-type (Pser_aminoTfrase_methanosarc)
Type: Family

These sequences represent a variant form of the serine biosynthesis enzyme phosphoserine aminotransferase, as found in a small number of distantly related species, including Caulobacter crescentus, Rhizobium loti (Mesorhizobium loti), and the archaeon Methanosarcina barkeri.
Phosphoserine aminotransferase, Mycobacterial-type (Pser_aminoTfrase_mycobac)
Type: Family

These sequences represent a putative variant form of the serine biosynthesis enzyme phosphoserine aminotransferase, as found in Mycobacterium tuberculosis and related high-GC Gram-positive bacteria.
Orotate phosphoribosyltransferase, bacterial (Orotate_PRibTrfase_bac)
Type: Family

This group of sequences are a distinct clade of bacterial orotate phosphoribosyltransferases. Members include the experimentally determined example from Thermus aquaticus and additional examples from Caulobacter crescentus, Helicobacter pylori (Campylobacter pylori), Rhizobium loti (Mesorhizobium loti), and related species.
Carbamoyl-phosphate synthase, small subunit (CarbamoylP_synth_ssu)
Type: Family

Carbamoyl phosphate synthase (CPSase) is a heterodimeric enzyme composed of a small and a large subunit (with the exception of CPSase III, see below). CPSase catalyses the synthesis of carbamoyl phosphate from biocarbonate, ATP and glutamine or ammonia, and represents the first committed step in pyrimidine and arginine biosynthesis in prokaryotes and eukaryotes, and in the urea cycle in most terrestrial vertebrates . This entry represents the small subunit of the glutamine-dependent form (

) of carbamoyl phosphate synthase. The small subunit catalyses the hydrolysis of glutamine to ammonia, which in turn used by the large chain to synthesize carbamoyl phosphate. The C-terminal domain of the small subunit of CPSase has glutamine amidotransferase activity.
Carbamoyl-phosphate synthase, large subunit (CPSase_lsu)
Type: Family

This entry represents glutamine-dependent CPSase (

) from prokaryotes and eukaryotes (CPSase II).

Carbamoyl phosphate synthase (CPSase) is a heterodimeric enzyme composed of a small and a large subunit (with the exception of CPSase III, see below). CPSase catalyses the synthesis of carbamoyl phosphate from biocarbonate, ATP and glutamine (

) or ammonia (

), and represents the first committed step in pyrimidine and arginine biosynthesis in prokaryotes and eukaryotes, and in the urea cycle in most terrestrial vertebrates . CPSase has three active sites, one in the small subunit and two in the large subunit. The small subunit contains the glutamine binding site and catalyses the hydrolysis of glutamine to glutamate and ammonia. The large subunit has two homologous carboxy phosphate domains, both of which have ATP-binding sites; however, the N-terminal carboxy phosphate domain catalyses the phosphorylation of biocarbonate, while the C-terminal domain catalyses the phosphorylation of the carbamate intermediate . The carboxy phosphate domain found duplicated in the large subunit of CPSase is also present as a single copy in the biotin-dependent enzymes acetyl-CoA carboxylase (

) (ACC), propionyl-CoA carboxylase (

) (PCCase), pyruvate carboxylase (

) (PC) and urea carboxylase (

).

Most prokaryotes carry one form of CPSase that participates in both arginine and pyrimidine biosynthesis, however certain bacteria can have separate forms. The large subunit in bacterial CPSase has four structural domains: the carboxy phosphate domain 1, the oligomerisation domain, the carbamoyl phosphate domain 2 and the allosteric domain . CPSase heterodimers from Escherichia coli contain two molecular tunnels: an ammonia tunnel and a carbamate tunnel. These inter-domain tunnels connect the three distinct active sites, and function as conduits for the transport of unstable reaction intermediates (ammonia and carbamate) between successive active sites . The catalytic mechanism of CPSase involves the diffusion of carbamate through the interior of the enzyme from the site of synthesis within the N-terminal domain of the large subunit to the site of phosphorylation within the C-terminal domain.

Eukaryotes have two distinct forms of CPSase: a mitochondrial enzyme (CPSase I) that participates in both arginine biosynthesis and the urea cycle; and a cytosolic enzyme (CPSase II) involved in pyrimidine biosynthesis. CPSase II occurs as part of a multi-enzyme complex along with aspartate transcarbamoylase and dihydroorotase; this complex is referred to as the CAD protein . The hepatic expression of CPSase is transcriptionally regulated by glucocorticoids and/or cAMP . There is a third form of the enzyme, CPSase III, found in fish, which uses glutamine as a nitrogen source instead of ammonia . CPSase III is closely related to CPSase I, and is composed of a single polypeptide that may have arisen from gene fusion of the glutaminase and synthetase domains .
Cobalamin-independent methionine synthase (Cobalamin-indep_Met_synthase)
Type: Family

Methionine synthases catalyse the the final step of methionine biosynthesis. Two apparently unrelated families of proteins catalyse this step: cobalamin-dependent methionine synthase, which catalyses the transfer of a methyl group from N5-methyltetrahydrofolate to L-homocysteine and requires cobalamin as a cofactor (MetH; 5-methyltetrahydrofolate:L-homocysteine S-methyltransferase;

) and cobalamin-independent methionine synthase, which catalyses the transfer of a methyl group from methyltetrahydrofolate to L-homocysteine without using an intermediate methyl carrier (MetE; 5-methyltetrahydropteroyltri-L-glutamate:L-homocysteine S-methyltransferase;

). These enzymes display no detectable sequence homology between them, but both require zinc for activation and binding to L-homocysteine. Organisms that cannot obtain cobalamin (vitamin B12) encode only the cobalamin-independent enzyme. Escherichia coli and many other bacteria express both enzymes . Mammals utilise only cobalamin-dependent methionine synthase, while plants and yeasts utilise only the cobalamin-independent enzyme.

This group represents cobalamin-independent methionine synthase . A group of archaeal proteins having substantial homology to the C-terminal region of this family is not included (see

).
Sarcosine oxidase, alpha subunit (Sarcosine_oxidase_asu)
Type: Family

This entry represents the alpha subunit of the heterotetrameric sarcosine oxidases (

). Five operons of such oxidases are found in Rhizobium loti (Mesorhizobium loti) and three in Agrobacterium tumefaciens, a high enough copy number to suggest that not all members share the same function. Sarcosine oxidase subunit alpha catalyses the oxidative demethylation of sarcosine to yield glycine, hydrogen peroxide and 5,10-methylenetetrahydrofolate .
Sarcosine oxidase subunit beta (SoxB)
Type: Family

These sequences represent the beta subunit of a family of known and putative heterotetrameric sarcosine oxidases. Five operons of such oxidases are found in Rhizobium loti (Mesorhizobium loti) and three in Agrobacterium tumefaciens, a high enough copy number to suggest that not all members share the same function. The model is designated as subfamily rather than equivalog for this reason.