SII-SWORD/CoKE huggingface dataset:
DNA-directed RNA polymerase, insert domain superfamily (RNApol_insert_sf)
Type: Homologous_superfamily

RNA polymerase (RNAP) II, which is responsible for all mRNA synthesis in eukaryotes, consists of 12 subunits. Subunits Rpb3 and Rpb11 form a heterodimer that is functionally analogous to the archaeal RNAP D/L heterodimer, and to the prokaryotic RNAP alpha (RpoA) subunit homodimer. In each case, they play a key role in RNAP assembly by forming a platform on which the catalytic subunits (eukaryotic Rpb1/Rpb2, and prokaryotic beta/beta') can interact .

The dimerisation domains differ between the different subunit families. In eukaryotic Rpb3, archaeal D and bacterial RpoA subunits (

), the dimerisation domain is comprised of a central insert domain, which interrupts an Rpb11-like domain (

), dividing it into two halves . In eukaryotic Rpb11 and archaeal L subunits, the insert domain is lacking, leaving the Rpb11-like domain intact and contiguous.
Ferredoxin thioredoxin reductase catalytic beta subunit superfamily (FTR_bsu_sf)
Type: Homologous_superfamily

Ferredoxin thioredoxin reductase is a [4FE-4S] protein present in organisms performing oxygenic photosynthesis, and plays an important role in the ferredoxin/thioredoxin regulatory chain. It converts an electron signal (photoreduced ferredoxin) to a thiol signal (reduced thioredoxin), regulating enzymes by reduction of specific disulphide groups. It catalyses the light-dependent activation of several photosynthetis enzymes. Ferredoxin thioredoxin reductase is a heterodimer of subunit alpha and subunit beta. Subunit alpha is the variable subunit, and beta is the catalytic chain .

The structure of the beta subunit has been determined and found to fold around the FeS cluster .
Elafin-like superfamily (Elafin-like_sf)
Type: Homologous_superfamily

Elafin is an elastase inhibitor. It contains a flat core and a flexible N-terminal extremity, the three-dimensional structure is formed by a central twisted β-hairpin accompanied by two external segments linked by the proteinase binding loop . This superfamily describes the C-terminal four-disulphide core or Whey Acidic Protein (WAP) domain, which harbours a functional motif involved in binding of proteinases and possibly other proteins .
BPG-independent phosphoglycerate mutase, domain B superfamily (PGAM_B_sf)
Type: Homologous_superfamily

Two distinct classes of phosphoglycerate mutases (PGMs) are known; those dependent on cofactor 2,3-bisphosphoglycerate (2,3-BPG) and those whose activity is independent of cofactor but dependent on the presence of divalent metal cations. The structure of 2,3-BPG-independent phosphoglycerate mutase (or phosphoglyceromutase or BPG-independent PGAM) (

) consists of an α/β type topology and is composed of two domains (A and B) with similar folds. The binding residues for both substrate and Mn2+, and the catalytic residues are located in the inter-domain cleft . This entry represents the B domain.
GTF2I-like repeat superfamily (GTF2I-like_rpt_sf)
Type: Homologous_superfamily

This region of sequence similarity is found up to six times in a variety of proteins including general transcription factor II-I (GTF2I). It has been suggested that this may be a DNA binding domain .

The structure of each GTF2I repeat is composed of an α(2)-β-α-β-α fold arranged in two layers (α/β) with antiparallel β-ribbon.
Nitrile hydratase alpha /Thiocyanate hydrolase gamma superfamily (CN_Hdrase_a/SCN_Hdrase_g_sf)
Type: Homologous_superfamily

Nitrile hydratases (

) are bacterial enzymes that catalyse the hydration of nitrile compounds to the corresponding amides. They are used as biocatalysts in acrylamide production, one of the few commercial scale bioprocesses, as well as in environmental remediation for the removal of nitriles from waste streams. Nitrile hydratases are composed of two subunits, alpha and beta, and are normally active as a tetramer, α(2)β(2). Nitrile hydratases contain either a non-haem iron or a non-corrinoid cobalt centre, both types sharing a highly conserved peptide sequence in the alpha subunit (CXLCSC) that provides all the residues involved in coordinating the metal ion. Each type of nitrile hydratase specifically incorporated its metal with the help of activator proteins encoded by flanking regions of the nitrile hydratase genes that are necessary for metal insertion. The Fe-containing enzyme is photo-regulated: in the dark the enzyme is inactivated due to the association of nitric oxide (NO) to the iron, while in the light the enzyme is active by photo-dissociation of NO. The NO is held in place by a claw setting formed through specific oxygen atoms in two modified cysteines and a serine residue in the active site . The cobalt-containing enzyme is unaffected by NO, but was shown to undergo a similar effect with carbon monoxide . Fe-and cobalt-containing enzymes also display different inhibition patterns with nitrophenols.

Thiocyanate hydrolase (SCNase) is a cobalt-containing metalloenzyme with a cysteine-sulphinic acid ligand that hydrolyses thiocyanate to carbonyl sulphide and ammonia .

The two enzymes, nitrile hydratase and SCNase, are homologous over regions corresponding to almost the entire coding regions of the genes: the beta and alpha subunits of thiocyanate hydrolase were homologous to the amino-and carboxyl-terminal halves of the beta subunit of nitrile hydratase, and the gamma subunit of thiocyanate hydrolase was homologous to the alpha subunit of nitrile hydratase .

This entry represents the structural domain of the alpha subunit of both iron- and cobalt-containing nitrile hydratases; the alpha subunit is a duplication of two structural repeats, each consisting of 4 layers, α/β/β/α . This structure is also found in the related protein, the gamma subunit of thiocyanate hydrolase (SCNase).
Inorganic pyrophosphatase superfamily (Pyrophosphatase_sf)
Type: Homologous_superfamily

Inorganic pyrophosphatase (

) (PPase) is the enzyme responsible for the hydrolysis of pyrophosphate (PPi) which is formed principally as the product of the many biosynthetic reactions that utilise ATP. All known PPases require the presence of divalent metal cations, with magnesium conferring the highest activity. Among other residues, a lysine has been postulated to be part of or close to the active site. PPases have been sequenced from bacteria such as Escherichia coli (homohexamer), Bacillus PS3 (Thermophilic bacterium PS-3) and Thermus thermophilus, from the archaebacteria Thermoplasma acidophilum, from fungi (homodimer), from a plant, and from bovine retina. In yeast, a mitochondrial isoform of PPase has been characterised which seems to be involved in energy production and whose activity is stimulated by uncouplers of ATP synthesis.

The sequences of PPases share some regions of similarities, among which is a region that contains three conserved aspartates that are involved in the binding of cations.
CAT RNA-binding domain superfamily (CAT_RNA-bd_dom_sf)
Type: Homologous_superfamily

This RNA binding domain is found at the N terminus of transcriptional antitermination proteins such as BglG, SacY and LicT. These proteins control the expression of sugar metabolising operons in Gram-positive and Gram-negative bacteria. This domain has been called the CAT (Co-AntiTerminator) domain. It binds as a dimer to short Ribonucleotidic Anti-Terminator (RAT) hairpin, each monomer interacting symmetrically with both strands of the RAT hairpin . In the full-length protein, CAT is followed by two phosphorylatable PTS regulation domains that modulate the RNA binding activity of CAT. Upon activation, the dimeric proteins bind to RAT targets in the nascent mRNA, thereby preventing abortive dissociation of the RNA polymerase from the DNA template .
Glutamine synthetase, N-terminal domain superfamily (Gln_synt_N_sf)
Type: Homologous_superfamily

Glutamine synthetase (

) (GS) plays an essential role in the metabolism of nitrogen by catalysing the condensation of glutamate and ammonia to form glutamine. This entry represents the glutamine synthetase N-terminal domain, which adopts a β-grasp fold and contributes to the substrate binding pocket of the enzyme .
YjeF N-terminal domain superfamily (YjeF_N_dom_sf)
Type: Homologous_superfamily

In bacteria or archaea, YjeF N-terminal domains occur either as single domain proteins or fused with other domains and are commonly associated with enzymes. YjeF N-terminal domains (also known as NAD(P)H-hydrate epimerase) are often fused to a YjeF C-terminal domain. It is a bifunctional enzyme that catalyses the epimerisation of the S- and R-forms of NAD(P)HX and the dehydration of the S-form of NAD(P)HX at the expense of ADP, which is converted to AMP .
CinA-like, C-terminal (CinA-like_C)
Type: Homologous_superfamily

This superfamily represents a C-terminal domain found in CinA (the first gene in the competence-inducible operon) and nicotinamide-nucleotide (NMN) amidohydrolase PncC.

CinA is thought to be specifically required at some stage in the process of natural transformation, a genetic recombination process .

NMN amidohydrolase (also known as NMN deamidase) is one of the key enzymes of the bacterial pyridine nucleotide cycle. This enzyme has been shown in S. oneidensis to be encoded by the gene PncC. It is further shown in S. oneidensis PncC, that the NMN deamidase activity resides in the C-terminal "CinA" domain, also known as the PncC domain . While multiple E. coli homologs to S. oneidensis PncC have been identified, only YgaD has been shown to posses NMN deaminase activity .
DNA polymerase III, psi subunit superfamily (DNA_pol_III_psi_sf)
Type: Homologous_superfamily

DNA-directed DNA polymerase (

) catalyzes DNA-template-directed extension of the 3'-end of an RNA strand by one nucleotide at a time. DNA polymerase III is a complex, multichain enzyme responsible for most of the replicative synthesis in bacteria. The enzyme also has 3' to 5' exonuclease activity. It has a core composed of alpha, epsilon and theta chains, that associate with a tau subunit which allows the core dimerization to form the PolIII' complex. PolIII' associates with the gamma complex (gamma, delta, delta', psi and chi chains) and with the beta chain. This superfamily represents the psi subunit, the small subunit of the DNA polymerase III holoenzyme in Escherichia coli and related species, whose exact function is not known. It appears to have a narrow taxonomic distribution, being restricted to the gammaproteobacteria. Its structure is composed of three layers (α/β/α) with parallel β-sheet of four strands.
Monomethylamine methyltransferase MtmB superfamily (MtmB_sf)
Type: Homologous_superfamily

Monomethylamine methyltransferase of the archaebacterium Methanosarcina barkeri contains a novel amino acid, pyrrolysine, encoded by the termination codon UAG . The structure of the enzyme reveals a homohexamer comprised of individual subunits with a TIM barrel fold. MtmB initiates the metabolism of monomethylamine by catalysing the transfer of the methyl group from monomethylamine to the corrinoid cofactor of MtmC .
Cytochrome b-c1 complex subunit 9 superfamily (QCR9_sf)
Type: Homologous_superfamily

Cytochrome b-c1 complex subunit 9 (QCR9) is a component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is part of the mitochondrial respiratory chain. It may interact with cytochrome c1 . QCR9 contains the single transmembrane helix structure.
DNA-binding protein Tfx superfamily, archaea (Tfx_DNA-bd_sf_arc)
Type: Homologous_superfamily

This entry represents a superfamily of Tfx DNA-binding proteins, which is restricted to the archaea. TfX has a 2-layer α/β topology. Homology among the members is strongest in the helix-turn-helix-containing N-terminal region. Tfx from Methanothermobacter thermautotrophicus (Methanobacterium thermoformicicum) is associated with the operon for molybdenum formyl-methanofuran dehydrogenase and binds a DNA sequence near its promoter.
CPI-17 superfamily (CPI-17_sf)
Type: Homologous_superfamily

Contractility of vascular smooth muscle depends on phosphorylation of myosin light chains, and is modulated by hormonal control of myosin phosphatase activity. Signaling pathways activate kinases such as PKC or Rho-dependent kinases that phosphorylate the myosin phosphatase inhibitor protein called CPI-17 (also known as protein phosphatase 1 regulatory subunit 14). Phosphorylation of CPI-17 at Thr-38 enhances its inhibitory potency 1000-fold, creating a molecular switch for regulating contraction .

CPI-17 forms a novel four-helix, V-shaped bundle comprised of a central anti-parallel helix pair (B/C helices) flanked by two large spiral loops formed by the N and C termini that are held together by another anti-parallel helix pair (A/D helices) stabilized by intercalated aromatic and aliphatic side-chains .
Fe-S hydro-lyase, tartrate dehydratase beta-type, catalytic domain superfamily (Fe-S_hydroAse_TtdB_cat_sf)
Type: Homologous_superfamily

This entry represents various Fe-S type hydro-lyases, including the beta subunit from both L-tartrate dehydratase (TtdB;

) and class 2 fumarate hydratase (FumC;

) . A number of Fe-S cluster-containing hydro-lyases share a conserved motif, including argininosuccinate lyase, adenylosuccinate lyase, aspartase, class I fumarate hydratase (fumarase), and tartrate dehydratase (see

). Proteins in this group represent a subset of closely related proteins or modules, including the Escherichia coli tartrate dehydratase beta chain and the C-terminal region of the class I fumarase (where the N-terminal region is homologous to the tartrate dehydratase alpha chain). The activity of the archaeal proteins in this group is unknown.
Luciferase-like domain superfamily (Luciferase-like_sf)
Type: Homologous_superfamily

Bacterial luciferase is a flavin monooxygenase that catalyses the oxidation of long-chain aldehydes and releases energy in the form of visible light, and which uses flavin as a substrate rather than a cofactor . Bacterial luciferase is an alpha/beta (LuxA/LuxB) heterodimer, where each individual subunit folds into a single TIM (β/α)8-barrel domain. There are structural similarities between bacterial luciferase and nonfluorescent flavoproteins (LuxF, FP390), alkanesulphonate monooxygenase (SsuD), and coenzyme F420-dependent terahydromethanopterin reductase, which make up clearly related families with somewhat different folds .
Phosphotransferase system, mannose-type IIA component superfamily (PTS_EIIA_man-typ_sf)
Type: Homologous_superfamily

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).

According to structural and sequence analyses, the PTS EIIA domain can be divided in different groups. The mannose class of EIIA consists of a single five-stranded mixed β sheet, flanked by helices on both sides . The phosphorylation site (His) is located at the end of the third β strand, in a shallow crevice lined with hydrophobic residues.

This entry represents the mannose-type EIIA domain superfamily. This type of domain can also be found in the multidomain protein dihydroxyacetone kinase DhaM from some bacteria .
Fumarylacetoacetase-like, C-terminal domain superfamily (Fumarylacetoacetase_C_sf)
Type: Homologous_superfamily

Fumarylacetoacetase (

; also known as fumarylacetoacetate hydrolase or FAH) catalyses the hydrolytic cleavage of a carbon-carbon bond in fumarylacetoacetate to yield fumarate and acetoacetate as the final step in phenylalanine and tyrosine degradation . This is an essential metabolic function in humans, the lack of FAH causing type I tyrosinaemia, which is associated with liver and kidney abnormalities and neurological disorders . The enzyme mechanism involves a catalytic metal ion, a Glu/His catalytic dyad, and a charged oxyanion hole . FAH folds into two domains: an N-terminal domain SH3-like β-barrel, and a C-terminal with an unusual fold consisting of three layers of β-sheet structures .

This superfamily represents the C-terminal domain of fumarylacetoacetase, as well as other domains that share a homologous α/β structure, including:

5-carboxymethyl-2-hydroxymuconate delta-isomerase (CHM isomerase;

), which catalyses the conversion of 5-carboxymethyl-2-hydroxymuconate to 5-carboxy-2-oxohept-3-enedioate .

5-oxopent-3-ene-1,2,5-tricarboxylate decarboxylase (OPET decarboxylase;

), which catalyses the conversion of 5-oxopent-3-ene-1,2,5-tricarboxylate to 2-oxohept-3-enedioate and carbon dioxide.

Bifunctional enzyme HpcE (OPET decarboxylase

/HHDD isomerase

), which is a duplication consisting of a tandem repeat of two FAH C-terminal-like domains. This enzyme is responsible for the degradation of 4-hydroxyphenylacetate, a product of tyrosine and phenylalanine metabolism also released by lignin catabolism .

2-keto-4-pentenoate hydratase MhpD (

; also known as 2-oxopent-4-enoate hydratase), which converts 4-hydroxy-2-oxopentanoate to 2-oxopent-4-enoate .

4-oxalocrotonate decarboxylase (4-OD;

), which catalyses the conversion of 4-oxalocrotonate to 2-oxopent-4-enoate and carbon dioxide .

2-oxo-hepta-3-ene-1,7-dioic acid hydratase, which hydrates the double bond of 2-oxo-hepta-3-ene-1,7-dioic acid to form 4-hydroxy-2-oxo-heptane-1,7-dioic acid in the catabolism of 4-hydroxyphenylacetic acid.

Oxaloacetate tautomerase FAHD1/2

that converts enol-oxaloacetate, a strong inhibitor of succinate dehydrogenase, to the physiological keto form of oxaloacetate .
Phosphotransferase system, glucitol/sorbitol-specific IIA component superfamily (PTS_IIA_glucitol/sorbitol_sf)
Type: Homologous_superfamily

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).

The Man family is unique in several respects among PTS permease families:

It is the only PTS family in which members possess a IID protein.

It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue.

Its permease members exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars.

This entry consists only of glucitol-specific transporters, and occur both in Gram-negative and Gram-positive bacteria. The system in Escherichia coli consists of a IIA protein, and a IIBC protein. This superfamily represents specifically the IIA component. The structure of this component is composed of a close barrel fold with mixed sheet; it has two overside connections and consists of two intertwinned structural repeats.
HHA superfamily (HHA_sf)
Type: Homologous_superfamily

This superfamily consists of haemolysin expression modulating protein (Hha) from Escherichia coli and its enterobacterial homologues, such as YmoA from Yersinia enterocolitica, and RmoA encoded on the R100 plasmid. These proteins act as modulators of bacterial gene expression. Members of the Hha/YmoA/RmoA family act in conjunction with members of the H-NS family, participating in the thermoregulation of different virulence factors and in plasmid transfer . Hha, along with the chromatin-associated protein H-NS, is involved in the regulation of expression of the toxin alpha-haemolysin in response to osmolarity and temperature . YmoA modulates the expression of various virulence factors, such as Yop proteins and YadA adhesin, in response to temperature. RmoA is a plasmid R100 modulator involved in plasmid transfer . Members of this family display striking similarity to the oligomerization domain of the H-NS proteins.
Phosphotransferase system, sorbose subfamily IIB component superfamily (PTS_IIB_sorbose-sp_sf)
Type: Homologous_superfamily

Bacterial phosphoenolpyruvate: sugar phosphotransferase system (PTS) transporters transport and concomitantly phosphorylate their sugar substrates, and typically consist of multiple subunits or protein domains . The Man family is unique in several respects among PTS permease families:

It is the only PTS family in which members possess a IID protein.

It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue.

Its permease members exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars.

The mannose permease of Escherichia coli, for example, can transport and phosphorylate glucose, mannose, fructose, glucosamine, N-acetylglucosamine, and other sugars. Other members of this can transport sorbose, fructose and N-acetylglucosamine. The active site histidine receives a phosphate group from the IIA subunit and transfers it to the substrate . This entry represents the IIB components of this family of PTS transporters . The structure of this component has three layers (α/β/α) with parallel β-sheet of six strands.
Insect antifreeze protein superfamily (Antifreeze_sf)
Type: Homologous_superfamily

Antifreeze proteins (AFPs) are a class of proteins that are able to bind to and inhibit the growth of macromolecular ice, thereby permitting an organism to survive subzero temperatures by decreasing the probability of ice nucleation in their bodies . These proteins have been characterised from a variety of organisms, including fish, plants, bacteria, fungi and arthropods. This entry represents insect AFPs of the type found in spruce budworm, Choristoneura fumiferana.

The structure of these AFPs consists of a left-handed β-helix with 15 residues per coil . The β-helices of insect AFPs present a highly rigid array of threonine residues and bound water molecules that can effectively mimic the ice lattice. As such, β-helical AFPs provide a more effective coverage of the ice surface compared to the α-helical fish AFPs.

A second insect antifreeze from Tenebrio molitor (

) also consists of β-helices, however in these proteins the helices form a right-handed twist; these proteins show no sequence homology to the current entry, but may act by a similar mechanism. The β-helix motif may be used as an AFP structural motif in non-homologous proteins from other (non-fish) organisms as well.