SII-SWORD/CoKE huggingface dataset:
Bacterial and archaeal 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide synthase (SAICAR_synt_PurC)
Type: Family

This entry represents a subfamily of 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide (SAICAR) synthases represented by the Thermotoga maritima (Tm) enzyme and E. coli PurC . SAICAR synthetase catalyzes the seventh step of the de novo biosynthesis of purine nucleotides (also reported as eighth step). It converts 5-aminoimidazole-4-carboxyribonucleotide (CAIR), ATP, and L-aspartate into 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide (SAICAR), ADP, and phosphate .
Large ribosomal subunit protein eL19, eukaryotic (Ribosomal_eL19_euk)
Type: Domain

This entry represents the structural domain of the large ribosomal subunit protein eL19 from eukaryotes and it is distinct from the ribosomal subunit L19, which is found in prokaryotes. It consists of two small globular domains connected by an extended segment. It is located toward the surface of the large subunit, with one exposed end involved in forming the intersubunit bridge with the small subunit. The other exposed end is involved in forming the translocon binding site, along with L22, L23, L24, L29, and L31e subunits .
Large ribosomal subunit protein eL19, archaeal (Ribosomal_eL19_arc)
Type: Domain

This entry represents the structural domain of the large ribosomal subunit protein eL19 from archaea. This protein is distinct from the ribosomal subunit L19, which is found in prokaryotes. It consists of two small globular domains connected by an extended segment. It is located toward the surface of the large subunit, with one exposed end involved in forming the intersubunit bridge with the small subunit. The other exposed end is involved in forming the translocon binding site, along with L22, L23, L24, L29, and L31e subunits .
Carbamoyl-phosphate synthase large chain, methylglyoxal synthase-like domain (MGS_CPS_CarB)
Type: Domain

This entry represents the methylglyoxal synthase-like domain from type II glutamine-dependent carbamoyl phosphate synthetase (CSP). CSP, a CarA and CarB heterodimer, catalyzes the production of carbamoyl phosphate which is subsequently employed in the metabolic pathways responsible for the synthesis of pyrimidine nucleotides or arginine. The MGS-like domain is the C-terminal domain of CarB and appears to play a regulatory role in CPS function by binding allosteric effector molecules, including UMP and ornithine .
Branched-chain aminotransferase (BCAT_family)
Type: Family

Branched-chain aminotransferase catalyses the transamination of the branched-chain amino acids leucine, isoleucine and valine to their respective alpha-keto acids, alpha-ketoisocaproate, alpha-keto-beta-methylvalerate and alpha-ketoisovalerate. The enzyme requires pyridoxal 5'-phosphate (PLP) as a cofactor to catalyze the reaction. It has been found that mammals have two forms of the enzyme - mitochondrial and cytosolic forms while bacteria contain only one form of the enzyme . The mitochondrial form plays a significant role in skeletal muscle glutamine and alanine synthesis and in interorgan nitrogen metabolism . Members of this entry are widely distributed in all three forms of life.
3-isopropylmalate dehydratase, swivel domain (IPMI_Swivel)
Type: Domain

3-isopropylmalate dehydratase (or isopropylmalate isomerase; IPMI;

) 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 .

This entry represents the aconitase-like swivel domain of 3-isopropylmalate dehydratase small subunit, which is believed to undergo swivelling conformational change in the enzyme mechanism.
3-Isopropylmalate dehydratase, catalytic domain (IPMI_cat)
Type: Domain

This entry represents the aconitase-like catalytic domain of 3-isopropylmalate dehydratase (IPMI) and related uncharacterised proteins.

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 .
Inositol monophosphatase (IMPase)
Type: Family

This entry includes inositol monophosphatase (IMPase) and related proteins which are a family of Mg
++
dependent phosphatases, inhibited by lithium, many of which may act on inositol monophosphate substrate. They dephosphorylate inositol phosphate to generate inositol, which may be recycled into inositol lipids; in eukaryotes IMPase plays a vital role in intracellular signaling . IMPase is one of the proposed targets of Li
+
therapy in manic-depressive illness . This family contains some bacterial members of the inositol monophosphatase family classified as SuhB-like. E. coli SuhB has been suggested to participate in posstranscriptional control of gene expression, and its inositol monophosphatase activity doesn't appear to be sufficient for its cellular function. It has been proposed, that SuhB plays a role in the biosynthesis of phosphatidylinositol in mycobacteria .
Ba3-like heme-copper oxidase subunit I (Ba3-like_Oxidase_I)
Type: Family

This entry represents ba3-like heme-copper oxidase subunit I.

The ba3 (Type B) family of heme-copper oxidases are transmembrane protein complexes in the respiratory chains of prokaryotes and some archaea which catalyze the reduction of O
2
and simultaneously pump protons across the membrane. It has been proposed that archaea acquired heme-copper oxidases through gene transfer from Gram-positive bacteria. The ba3 family contains oxidases that lack the conserved residues that form the D- and K-pathways in CcO and ubiquinol oxidase. Instead they contain a potential alternative K-pathway. Additional proton channels have been proposed for this family of oxidases but none have been identified definitively .
Cytochrome c oxidase subunit I domain (Cyt_c_oxase_su1_dom)
Type: Domain

Cytochrome c oxidase (

) is a key enzyme in aerobic metabolism. Proton pumping haem-copper oxidases represent the terminal, energy-transfer enzymes of respiratory chains in prokaryotes and eukaryotes. The CuB-haem a3 (or haem o) binuclear centre, associated with the largest subunit I of cytochrome c and ubiquinol oxidases (

), is directly involved in the coupling between dioxygen reduction and proton pumping .
Some terminal oxidases generate a transmembrane proton gradient across the plasma membrane (prokaryotes) or the mitochondrial inner membrane (eukaryotes).

The enzyme complex consists of 3-4 subunits (prokaryotes) up to 13 polypeptides (mammals) of which only the catalytic subunit (equivalent to mammalian subunit I (CO I) is found in all haem-copper respiratory oxidases. The presence of a bimetallic centre (formed by a high-spin haem and copper B) as well as a low-spin haem, both ligated to six conserved histidine residues near the outer side of four transmembrane spans within CO I is common to all family members . In contrast to eukaryotes the respiratory chain of prokaryotes is branched to multiple terminal oxidases. The enzyme complexes vary in haem and copper composition, substrate type and substrate affinity. The different respiratory oxidases allow the cells to customize their respiratory systems according to a variety of environmental growth conditions .

This entry represents a domain found in cytochrome c oxidase subunit I.
Cytochrome c oxidase subunit III domain (Cyt_c_oxase_su3_dom)
Type: Domain

Cytochrome c oxidase (

) is the terminal enzyme of the respiratory chain of mitochondria and many aerobic bacteria. It catalyses the transfer of electrons from reduced cytochrome c to molecular oxygen:

4 cytochrome c
+2
+ 4 H
+
+ O
2
--> 4 cytochrome c
+3
+ 2 H
2
O

This reaction is coupled to the pumping of four additional protons across the mitochondrial or bacterial membrane .

Cytochrome c oxidase is an oligomeric enzymatic complex that is located in the mitochondrial inner membrane of eukaryotes and in the plasma membrane of aerobic prokaryotes. The core structure of prokaryotic and eukaryotic cytochrome c oxidase contains three common subunits, I, II and III. In prokaryotes, subunits I and III can be fused and a fourth subunit is sometimes found, whereas in eukaryotes there are a variable number of additional small polypeptidic subunits . The functional role of subunit III is not yet understood.

As the bacterial respiratory systems are branched, they have a number of distinct terminal oxidases, rather than the single cytochrome c oxidase present in the eukaryotic mitochondrial systems. Even though the cytochrome o complex oxidises quinol (ubiquinol) and does not catalyse the oxidation of reduced cytochrome c, they belong to the same haem-copper oxidase superfamily as cytochrome c oxidases. Members of this family share sequence similarities in all three core subunits: subunit I is the most conserved subunit, whereas subunit II is the least conserved .

This entry represents a structural domain found in subunit III of cytochrome c oxidase specifically.
Ubiquinol oxidase subunit III domain (Ubiquinol_oxase_su3_dom)
Type: Domain

Ubiquinol oxidase is a multi-chain transmembrane protein located in the cell membrane and one of several aerobic bacterial terminal oxidases . This complex couples oxidation of reduced quinones to the reduction of molecular oxygen to water, and the pumping of protons to form the proton gradient utilised for ATP production. aa3-type oxidases contain two haem A cofactors as well as copper atoms at the active site.

Quinone oxidases feature four subunits in contrast to the 13 subunit bovine cytochrome c oxidase (CcO). Subunits I, II and III of ubiquinol oxidase are homologous to the corresponding subunits in bovine CcO . Although not required for catalytic activity, subunit III appears to be involved in assembly of the multimer complex .

This entry represents a domain found in ubiquinol oxidase subunit III. While this signature predominantly matches the ubiquinol oxidase version of the domain, it also includes some cytochrome c oxidase homologues.
Electron transfer flavoprotein, alpha subunit, N-terminal (ETF_alpha_N)
Type: Domain

This entry refers to an N-terminal domain found predominantly in the alpha subunit of ETF.

The electron transfer flavoprotein (ETF) serves as a specific electron acceptor for various mitochondrial dehydrogenases. ETF transfers electrons to the main respiratory chain via ETF-ubiquinone oxidoreductase . ETF is an heterodimer that consists of an alpha and a beta subunit which binds one molecule of FAD per dimer. A similar system also exists in some bacteria. The homologous pair of proteins (FixA/FixB) are essential for nitrogen fixation . The alpha subunit of ETF is structurally related to the bacterial nitrogen fixation protein fixB which could play a role in a redox process and feed electrons to ferredoxin .
Electron transfer flavoprotein, beta subunit, N-terminal (ETF_beta_N)
Type: Domain

This entry refers to an N-terminal domain found predominantly in the beta subunit of ETF.

The electron transfer flavoprotein (ETF) serves as a specific electron acceptor for various mitochondrial dehydrogenases. ETF transfers electrons to the main respiratory chain via ETF-ubiquinone oxidoreductase . ETF is an heterodimer that consists of an alpha and a beta subunit which binds one molecule of FAD per dimer. A similar system also exists in some bacteria. The homologous pair of proteins (FixA/FixB) are essential for nitrogen fixation. The beta subunit protein is distantly related to and forms a heterodimer with the alpha subunit .
Cobyric acid synthase, glutamine amidotransferase type 1 (CobQ_GATase1)
Type: Domain

Vitamin B12 (cobalamin) is an essential nutrient that serves as a co-factor for enzymatic reactions. The biosynthesis of this coenzyme is a complex process that is confined to certain prokaryotes and requires circa 25 different enzymes. During the assembly, six amide groups are introduced at the a, b, c, d, e and g carboxylates. In the aerobic and anaerobic biosynthetic pathways, the six amidation steps are carried out by two separate enzymes. Cobyrinic acid a,c-diamide synthethase (cbiA and cobB) is responsible for the introduction of the two amide groups at the a and c positions in either cobyrinic acid or hydrogenobrynic acid. The amidation of the b, d, e, and g carboxylate groups in adenosyl-Cob(I)yrinic acid a,c-diamide is catalysed by cobyric acid synthetase (cbiP and cobQ). Many of the enzymatic reactions for the aerobic biosynthesis of cobalamin are known for Pseudomonas denitrificans. The anaerobic pathway is found in other bacteria and archaea, such as Salmonella, Bacillus, Methanococcus and Propionibacterium species .

The cobB and cobQ family proteins contain two separate domains involved in cobalamin biosynthesis, i.e. a synthetase domain including ATP-binding motifs in the N-terminal part and a glutamine amidotransferase (GATase) domain in the C-terminal part. The GATase domain is involved in glutamine binding, hydrolysis and transfer of the resulting ammonia to an acceptor. This domain resembles the GATases of class I, which are characterised by a conserved Cys-His-Glu active site, but the cobBQ-type GATases lack the Glu residue in this typical triad . The cobBQ-type GATase domain shows also similarity to other GATase type 1 related domains/families, like PdxT/SNO, gamma-glutamyl hydrolase and PfpI endopeptidase.

Some proteins known to contain a cobBQ-type GATase domain:

Salmonella typhimurium cobyrinic acid a,c-diamide synthase (cbiA), which is responsible for the amidation of carboxylic groups at positions a and c of either cobyrinic acid or hydrogenobrynic acid.

P. denitrificans cobyrinic acid a,c-diamide synthase (cobB), which is responsible for the amidation of carboxylic groups at positions a and c of either cobyrinic acid or hydrogenobrynic acid.

S. typhimurium cobyric acid synthase (cbiP), which catalyses amidations at positions b, d, e, and g on adenosylcobyrinic a,c-diamide.

P. denitrificans cobyric acid synthase (cobQ), which catalyses amidations at positions b, d, e, and g on adenosylcobyrinic a,c-diamide.

The entry represents the type 1 glutamine amidotransferase (GATase1) domain found in cobyric acid synthase (CobQ).
Stimulator of interferon genes protein homolog, C-terminal (STING_C)
Type: Domain

This entry represents the C-terminal domain of STING homologues from arthropods.

STING (stimulator of interferon genes, also known as MITA, ERIS, MPYS and TMEM173) is a master regulator that mediates cytokine production in response to microbial invasion by directly sensing bacterial secondary messengers such as the cyclic dinucleotide bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) and leading to the activation of IFN regulatory factor 3 (IRF3) through TANK-binding kinase 1 (TBK1) stimulation . STING is also a signaling adaptor in the IFN response to cytosolic DNA. This detection of foreign materials is the first step to a successful immune responses. STING is localized in the ER and comprised of an predicted N-terminal transmembrane region and a C-terminal c-di-GMP binding domain .
Disulphide bond isomerase, DsbC/G (DiS-bond_Isoase_DsbC/G)
Type: Family

Disulfide bond isomerases DsbC and DsbG are V-shaped homodimeric proteins containing a redox active CXXC motif imbedded in a TRX fold. They function as protein disulfide isomerases and chaperones in the bacterial periplasm to correct non-native disulfide bonds formed by DsbA and prevent aggregation of incorrectly folded proteins . DsbC and DsbG are kept in their reduced state by the cytoplasmic membrane protein DsbD, which utilizes the TRX/TRX reductase system in the cytosol as a source of reducing equivalents . DsbG differ from DsbC in that it has a more limited substrate specificity, and it may preferentially act later in the folding process to catalyze disulfide rearrangements in folded or partially folded proteins .

Also included in this entry is the predicted protein TrbB, whose gene was sequenced from the enterohemorrhagic E. coli type IV pilus gene cluster, which is required for efficient plasmid transfer. TrbB may be a disulfide bond isomerase that functions in the conjugative process by facilitating proper folding of a subset of F-plasmid-encoded proteins in the periplasm .
Translin (Translin)
Type: Family

Translin (also known as TB-RBP for Testis Brain RNA-binding protein, a mouse orthologue), is a paralogue of its binding partner protein TRAX (translin-associated factor-X) and together they form oligomeric complexes known as C3PO proteins (for component 3 promoter of RNA-induced silencing complex or RISC) . DNA damage has been proposed to stimulate transport of Translin into nuclei. It binds to RNA and single-stranded DNA, and its selectivity is modulated by interactions with GTP and TRAX. Translin may also regulate dendritic trafficking of BDNF RNAs as well as function as a key activator of siRNA-mediated silencing in Drosophila . Translin and Trax participate in a variety of nucleic acid metabolism pathways in addition to RNAi and have been implicated in a wide range of biological activities, including mRNA processing, cell growth regulation, spermatogenesis, neuronal development/function, genome stability regulation and carcinogenesis ; however, their precise role in some of the processes remains unclear.
Exocyst complex component Exo84 (Exo84)
Type: Family

The exocyst is a highly conserved complex composed of Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70, and Exo84, which was originally identified in Saccharomyces cerevisiae . Mammalian homologues of all eight exocyst proteins have been identified . The exocyst is required for exocytosis; it mediates tethering of the secretory vesicle before docking and fusion with the plasma membrane .

Exo84 is also involved in pre-mRNA splicing and is required for epithelial polarity in Drosophila .
Aromatic prenyltransferase (ABBA)
Type: Family

This family is also known as the ABBA (α-β-β-α) fold superfamily. Characterised members catalyse the prenylation of phenols, naphthalenes, phenazines, indole, tyrosine, and xanthone derivatives .
Tryptophan prenyltransferase ComQ (ComQ)
Type: Family

Characterised proteins in this subgroup are involved in the maturation of ComX, part of a major quorum-sensing system that regulates the development of genetic competence, by geranylation or farnesylation of a conserved tryptophan in ComX .
RuBisCO (RuBisCO)
Type: Family

Structurally characterised enzymes in the RuBisCO superfamily are dimers with an active site located at the interface of the N-terminal α+β domain of one polypeptide and the C-terminal TIM β/α-barrel of the second polypeptide. Though most of the enzymes in the superfamily are thought to function as D-Ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO), a smaller number of enzymes, termed the RuBisCO-like proteins, do not catalyse carboxylation reactions. Despite these differences, superfamily enzymes share a common active site architecture used to stabilise an enolate intermediate .
Avilamycin epimerase (Avilamycin_epimerase)
Type: Family

The biosynthesis of avilamycin, an oligosaccharide antibiotic, starts with the formation of a disaccharide synthesised from D-glucose. AviX12 is involved in C-2 epimerization of the glucose moiety after the whole avilamycin molecule has been formed to form the d-mannose stereoisomer. Unusually, the C-2 carbon is an uncativated centre, and it is thought that AviX12 generates the 5'deoxyadenosyl radical, which abstracts a hydrogen atom a position C-2 of the mannose moiety to form a radical intermediate. This intermediate undergoes epimerization by an unknown mechanism .

avilamycin A precursor + S-adenosyl-L-methionine zwitterion ->avilamycin A+5'-deoxyadenosine + L-methionine zwitterion

This family includes avilamycin epimerase AviX12 and related proteins from Actinobacteria.
Glycerol dehydratase activase (Glycerol_dehydratase_activase)
Type: Family

Glycerol dehydratase activase (GD-AE) contains the canonical [Fe4S4] binding motif and two additional ferredoxin-like [4Fe-4S] cluster binding domains. It is an organic radical activase that forms a glycyl radical on the B12-independent glycerol dehydratase and, counter to the paradigm of the common activation step of the Radical SAM superfamily, produces 5'-deoxy-5'-(methylthio)adenosine (MTA) and 2-aminobutyrate rather than 5'-deoxyadenosine (5'-dA) and methionine. The formation of MTA rather than 5'-dA is somewhat analogous to the Radical SAM 3-amino-3-carboxypropyl radical forming Superfamily and thus a similar radical intermediate has been proposed. This alternative reductive cleavage pathway for SAM is surprising given the structural similarities between the GD and PFL at the level of both primary and tertiary structure, it is difficult at this time to determine exactly why the GD-AE follows a different reductive cleavage pathway during glycyl radical formation. The precise identity of the radical intermediate in the GD-AE activation mechanism is still under investigation .

glycerol dehydratase (inactive) + S-adenosyl-L-methioninate + 1,5-dihydroflavin ->glycerol dehydratase (active) + L-methionine zwitterion + 5'-deoxyadenosine+semiquinone
Carbapenem intermediate methyltransferase, ThnP-like (ThnP-like)
Type: Family

ThnP is thought to be responsible for the vitamin B12 dependent methylation of the beta-lactam ring in the thienamycin (thn) gene cluster. It is currently not known what the methyl donor is, but in keeping with the other B12-dependent methyltransferases, it has been shown as methylcobalamin here. Mutagenesis performed on the thnP gene product demonstrated that thnP is essential for thienamycin biosynthesis. However, the mutant retained the ability to produce cephamycin, thus showing that ThnP is not involved in cephamycin C biosynthesis .
Gentamicin-like N-methyltransferase (GntE-like)
Type: Family

These enzymes all perform the cobalamin-dependent N-methyltransferase that transforms gentamicin A into gentamicin X2 .

Gentamicin A2 + 2(S-adenosyl-L-methionine zwitterion) ->gentamycin A + S-adenosyl-L-homocysteine zwitterion + L-methionine zwitterion + 5'-deoxyadenosine
Galactarate dehydratase 2 (Galactarate_dehydratase_2)
Type: Family

Enzymes in the galactarate dehydratase 2 family catalyze the dehydration of galactarate. The product of this reaction is the enantiomer of the product of the galactarate dehydratase reaction catalyzed by the L-talarate/galactarate dehydratase family in the mandelate racemase subgroup. Though the overall reaction catalyzed is the same as that of enzymes in the galactarate dehydratase 3 family, a distinct set of catalytic residues are used by enzymes in families 2 and 3 .

galactarate(2-) -> 3-deoxy-D-threo-hex-2-ulosarate(2-) + H
2
O