SII-SWORD/CoKE huggingface dataset:
rRNA adenine dimethylase-like, C-terminal (rRNA_Ade_diMease-like_C)
Type: Homologous_superfamily

KsgA is a universally conserved rRNA adenine dimethyltransferase that catalyses the transfer of a total of four methyl groups from S-adenosyl-l-methionine (S-AdoMet) to two adjacent adenosine bases in 16S rRNA. This enzyme and the resulting modified adenosine bases appear to be conserved in all species of eubacteria, eukaryotes, and archaebacteria, and in eukaryotic organelles. The KsgA enzymes are homologous to another family of RNA methyltransferases, the Erm enzymes, which methylate a single adenosine base in 23S rRNA .

This superfamily represents a rRNA adenine dimethylase-like domain present in these enzymes, which consists of four α-helices and one 3(10)-helix and forms a cleft with the N-terminal domain and is thought to stabilise it. Other studies have suggested that due to the positively charged surface patch, the C-terminal domain may be involved in recognition and binding of the ribosomal rRNA substrate, and mediates substrate specificity .
BaiN-like, insert domain superfamily (BaiN-like_dom_sf)
Type: Homologous_superfamily

This entry represents two structural (β-barrel and H2TH α-helical) domains that are found inserted within a Rossmann fold-like domain.

This domain is found in 3-dehydro-bile acid delta(4,6)-reductase from Clostridium scindens (BaiN), Ribosomal RNA dihydrouridine synthase (rdsA) from Escherichia coli and Aminoacetone oxidase (aao(So)) from Streptococcus cristatus.

BaiN is involved in the secondary bile acid metabolism. It catalyses two subsequent reductions of the double bonds within the bile acid A/B rings of 3-oxochol-4,6-dien-24-oyl-CoA and 12alpha-hydroxy-3-oxochol-4,6-dien-24-oyl-CoA to yield 3-oxocholan-24-oyl-CoA and 12alpha-hydroxy-3-oxocholan-24-oyl-CoA, respectively .

RdsA catalyses the synthesis of 5,6-dihydrouridine (D) at position 2449 in 23S rRNA. It can use NADH as a source of reducing equivalents but not NADPH .

Aao(So) is a flavoprotein thought to catalyse the condensation of two aminoacetone molecules to form 3,6-dimethyl-2,5-dihydropyrazine, which is then oxidised to 2,5-dimethylpyrazine, suggesting a role in a microbial defence pathway that avoids toxic methylglyoxal production. It has low aminoacetone oxidase activity and can generate hydrogen peroxide from aminoacetone, peptone, and several L-amino acids, indicating a potential function in oxidative metabolism and antimicrobial defence. However, it shows little to no activity toward substrates like L-malate, oxaloacetate, or alpha-aminobutyrate. Overall, it contributes to antioxidant defence mechanisms .
Yap1 redox domain superfamily (Yap1_redox_dom_sf)
Type: Homologous_superfamily

The transcription factor Yap1 is a central regulator of the response to oxidative stress in Saccharomyces cerevisiae. In the active oxidized form, a nuclear export signal (NES) in the carboxy-terminal cysteine-rich domain is masked by disulphide-bond-mediated interactions with a conserved amino-terminal α-helix. Upon reduction of the disulphide bonds, Yap1 undergoes a change that exposes the NES and allows redistribution to the cytoplasm . This entry represents a redox-regulated domain superfamily of Yap1.
Aspartyl/glutamyl-tRNA(Asn/Gln) amidotransferase, C-terminal, domain 2 (GatB_Yqey_C_2)
Type: Homologous_superfamily

Glutamyl-tRNA(Gln) amidotransferase (Gat;

) provides a means of producing correctly charged Gln-tRNA(Gln) through the transamidation of mis-acylated Glu-tRNA(Gln) in organisms which lack glutaminyl-tRNA synthetase . The reaction takes place in the presence of glutamine and ATP through an activated gamma-phospho-Glu-tRNA(Gln). The enzyme is composed of three subunits: A (an amidase), B and C. It also exists in eukaryotes as a protein targeted to the mitochondria.

The heterotrimer GatABC is involved in converting Glu to Gln and/or Asp to Asn, when the amino acid is attached to the appropriate tRNA. In Lactobacillus, GatABC is responsible for producing tRNA(Gln). In Archaea, GatABC is responsible for producing tRNA(Asn), while GatDE is responsible for producing tRNA(Gln). In lineages that include Thermus, Chlamydia, or Acidithiobacillus, the GatABC complex catalyses both tRNA(Gln) and tRNA(Asn).

This entry represents the extreme C-terminal structural domain of GatB and GatE subunits. It forms a predominantly α-helical structure.
Helix-hairpin-helix, base-excision DNA repair, C-terminal (HhH_base_excis_C)
Type: Homologous_superfamily

This entry represents the extreme C terminus of the helix-hairpin-helix base-excision DNA repair enzyme family, including the DNA glycosylases and lyases .
Na+/H+ antiporter domain superfamily (Na/H_antiporter_dom_sf)
Type: Homologous_superfamily

NhaA is a sodium ion/proton antiporter that uses the proton electrochemical gradient to expel sodium ions from the cytoplasm and functions primarily in the adaptation to high salinity at alkaline pH. NhaA is also believed to be responsible for adaptation to alkaline pH when sodium is available. NhaA is one of the three known sodium ion/proton antiporters in Escherichia coli along with NhaB and ChaA, though there are other mechanisms for Na+ extrusion such as NDH-I complicating the determination of the precise roles of each of the transporters .

This entry represents the structural domain superfamily found in the Na+/H+ family of antiporters.
Peptidase S51, dipeptidase E (Peptidase_S51_dipeptidase-E)
Type: Family

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes . They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence . Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases .

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base . The geometric orientations of the catalytic residues are similar between families, despite different protein folds . The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) .

This entry represents serine peptidases belonging to MEROPS peptidase family S51 (dipeptidase E, clan PC). They hydrolyse peptides bond in dipeptides where the first amino acid is aspartate . The three-dimensional structure of Salmonella typhimurium aspartyl dipeptidase, peptidase E, has been reported at 1.2A resolution. The structure of this 25kDa enzyme consists of two mixed b-sheets forming a V, flanked by six a-helices. The active site contains a Ser-His-Glu catalytic triad .
NADPH-cytochrome p450 reductase, FAD-binding, alpha-helical domain superfamily (NADPH_Cyt_P450_Rdtase_alpha)
Type: Homologous_superfamily

This superfamily represents the α-helical subdomain (domain 3) of the FAD-binding domain which can be found in NADPH-cytochrome P450 reductases , nitric oxide synthases, NADPH-dependent diflavin oxidoreductases, and pyruvate dehydrogenases.
3'5'-cyclic nucleotide phosphodiesterase, conserved site (PDEase_CS)
Type: Conserved_site

3'5'-cyclic nucleotide phosphodiesterases (

) (PDEases) catalyse the hydrolysis of cAMP or cGMP to the corresponding nucleoside 5' monophosphates . There are at least seven different subfamilies of PDEases :

Type 1, calmodulin/calcium-dependent PDEases.

Type 2, cGMP-stimulated PDEases.

Type 3, cGMP-inhibited PDEases.

Type 4, cAMP-specific PDEases.

Type 5, cGMP-specific PDEases.

Type 6, rhodopsin-sensitive cGMP-specific PDEases.

Type 7, High affinity cAMP-specific PDEases.

All of these forms seem to share a conserved domain of about 270 residues. This entry has a signature pattern from a stretch of 12 residues that contains two conserved histidines.

The PDEase catalytic domains adopt a compact α-helical structure
consisting of 16 α-helices that can be divided into three subdomains. The active site of PDEases is a deep pocket formed by the tree
subdomains and can be divided into two major subpockets for binding of
divalent metals and substrate/inhibitors, respectively. The active site of all
PDEase domains contains two divalent metal ions: zinc and probably magnesium
.
Vta1/Callose synthase, N-terminal domain superfamily (Vta1/CALS_N_sf)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain of vacuolar protein sorting-associated proteins and callose synthases. This domain contains seven α helices arranged into two antiparallel three-helix bundle modules. It has been proposed that vacuolar protein sorting-associated protein Vta1 interacts with Vps60 and Vps46/Did2 via this N-terminal domain .
Orbivirus inner capsid protein VP7, N-terminal (Orbi_VP7_capsid_N)
Type: Homologous_superfamily

The bluetongue virus (BTV) is a representative of the orbivirus genus of the Reoviridae. The crystal structure of VP7 from BTV serotype 10 reveals that the central one third of the polypeptide chain (residues 121-249) is folded into a β-sandwich. The rest of the polypeptide (residues 1-120 and 250-349) is composed of nine α-helices and long extended loops .

This superfamily represents the N-terminal domain, consisting of five α-helices.
Orbivirus inner capsid protein VP7, C-terminal (Orbi_VP7_capsid_C)
Type: Homologous_superfamily

The bluetongue virus (BTV) is a representative of the orbivirus genus of the Reoviridae. The crystal structure of VP7 from BTV serotype 10 reveals that the central one third of the polypeptide chain (residues 121-249) is folded into a β-sandwich. The rest of the polypeptide (residues 1-120 and 250-349) is composed of nine α-helices and long extended loops .

This superfamily represents the C-terminal domain consisting of four α-helices.
GTP-binding protein, orthogonal bundle domain superfamily (GTP-bd_ortho_bundle_sf)
Type: Homologous_superfamily

This superfamily represents a orthogonal bundle domain found in some GTP-binding proteins, including YlgF from Bacillus subtilis.
Tetrahydrodipicolinate-N-succinyltransferase, chain A, domain 1 (THP_succinylTrfase_dom1)
Type: Domain

This entry represents the N-terminal domain of the enzyme tetrahydrodipicolinate-N-succinyltransferase .
Homospermidine synthase-like, C-terminal (Homospermid_syn-like_C)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain, which is a 2-layer α/β sandwich, found in homospermidine synthase and related proteins.
Serine protease, chymotrypsin-like serine protease, C-terminal (Chymotrypsin-like_C)
Type: Homologous_superfamily

The replicase polyprotein 1ab is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.

Nsp1 is essential for viral subgenomic mRNA synthesis.

Nsp2 cysteine proteinase which cleaves the Nsp2/Nsp3 site in the polyprotein. Also displays deubiquitinating and deISGylase activities. The deubiquitinating activity cleaves both ubiquitinated and ISGylated products and may therefore regulate ubiquitin and ISG15 dependent host innate immunity.

The 3C-like serine proteinase chain (Nsp4) is responsible for the majority of cleavages as it cleaves the C terminus of the polyprotein.

The helicase chain, which contains a zinc finger structure, displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity .

This superfamily represents the C-terminal domain of chymotrypsin-like serine proteinase Nsp4. Nsp4 contains two β-barrels, known as N- and C-terminal barrels, as well as a unique C-terminal domain. The C-terminal domain consists of two short pairs of β-strands and two α-helices. It interacts with the C-terminal barrel through an interface consisting of conserved hydrophobic residues: Leu-105 and Leu-112 from the C-terminal β-barrel and Val-158, Leu-163, Phe-167, Ile-182, Leu-196, and Ile-197 from the C-terminal domain. There is also an exposed patch of conserved solvent-exposed hydrophobic residues that may form part of the interface with Nsp5 in the Nsp4-5 intermediate . This hydrophobic patch may also mediate interactions with Nsp2, which associates with Nsp3-8 to induce cleavage of the Nsp4-5 site by Nsp4 .
Ubiquinol-cytochrome C reductase hinge domain (Ubol_cytC_Rdtase_hinge_dom)
Type: Domain

The ubiquinol-cytochrome C reductase complex (cytochrome bc1 complex) is a respiratory multienzyme complex . The bc1 complex contains 11 subunits; 3 respiratory subunits (cytochrome B, cytochrome C1, Rieske protein), 2 core proteins and 6 low molecular weight proteins. This family represents the 'hinge' protein of the complex which is thought to mediate formation of the cytochrome c1 and cytochrome c complex. Proteins in this entry form an α-helical hairpin.

This entry represents the structural domain found in these proteins.
Inosine/uridine-preferring nucleoside hydrolase (IUNH)
Type: Family

Inosine-uridine preferring nucleoside hydrolase (

) (IU-nucleoside hydrolase or IUNH) is an enzyme first identified in protozoan that catalyses the hydrolysis of all of the commonly occuring purine and pyrimidine nucleosides into ribose and the associated base, but has a preference for inosine and uridine as substrates. This enzyme is important for these parasitic organisms, which are deficient in
de novo
synthesis of purines, to salvage the host purine nucleosides. IUNH from Crithidia fasciculata has been sequenced and characterised, it is an homotetrameric enzyme of subunits of 34 Kd. An histidine has been shown to be important for the catalytic mechanism, it acts as a proton donor to activate the hypoxanthine leaving group.

A highly conserved region located in the N-terminal extremity contains four conserved aspartates that have been shown to be located in the active site cavity.

IUNH is evolutionary related to a number of uncharacterised proteins from various biological sources.
Transcriptional regulator MarR-type, conserved site (Tscrpt_reg_MarR-type_CS)
Type: Conserved_site

This entry represents a 34 residue conserved site showing high conservation within this family.

The MarR-type HTH domain is a DNA-binding, winged helix-turn-helix (wHTH) domain of about 135 amino acids present in transcription regulators of the MarR/SlyA family, involved in the development of antibiotic resistance. The MarR family of transcription regulators is named after Escherichia coli MarR, a repressor of genes which activate the multiple antibiotic resistance and oxidative stress regulons, and after slyA from Salmonella typhimurium and E. coli, a transcription regulator that is required for virulence and survival in the macrophage environment. Regulators with the MarR-type HTH domain are present in bacteria and archaea and control a variety of biological functions, including resistance to multiple antibiotics, household disinfectants, organic solvents, oxidative stress agents and regulation of the virulence factor synthesis in pathogens of humans and plants. Many of the MarR-like regulators respond to aromatic compounds .

The crystal structures of MarR, MexR and SlyA have been determined and show a winged HTH DNA-binding core flanked by helices involved in dimerisation. The DNA-binding domains are ascribed to the superfamily of winged helix proteins, containing a three (four)-helix (H) bundle and a three-stranded antiparallel β-sheet (B) in the topology: H1-(H1')-H2-B1-H3-H4-B2-B3-H5-H6. Helices 3 and 4 comprise the helix-turn-helix motif and the β-sheet is called the wing. Helix 4 is termed the recognition helix, like in other HTHs where it binds the DNA major groove. The helices 1, 5 and 6 are involved in dimerisation, as most MarR-like transcription regulators form dimers .
DNA-binding protein Dps, conserved site (DPS_DNA-bd_CS)
Type: Conserved_site

Escherichia coli protein Dps is a DNA-binding protein, synthesized during prolonged starvation, that seems to protect DNA from oxidative damage. Dps binds DNA without any apparent sequence specificity. It is a protein of about 19 Kd that associates into a complex of 12 subunits forming two stacked hexameric rings.

Proteins similar to Dps have been found in other bacteria:

Bacillus subtilis protein MrgA.

Antigen TpF1/TyF1 from Treponema pallidum.

Haemophilus ducreyi fine tangled pili major subunit (gene ftpA).

Helicobacter pylori neutrophil-activating protein A (gene napA).

Listeria innocua non-heme iron-containing ferritin.

Synechococcus elongatus (strain PCC 7942) (Anacystis nidulans R2) nutrient-stress induced DNA binding protein (gene dpsA).

A low-temperature induced protein from Anabaena variabilis.

Haemophilus influenzae hypothetical protein HI1349.

Synechocystis sp. (strain PCC 6803) hypothetical protein Slr1894.

A hypothetical protein encoded in the 5' region of a gene coding for a bromoperoxidase, in plasmid pOP2621 of Streptomyces aureofaciens.

All these proteins share a conserved region of about 50 residues in their central region. This entry corresponds to two conserved sites derived from both extremities of that region.
Deoxynucleotide monophosphate kinase, N-terminal (DNMP_kinase_N)
Type: Homologous_superfamily

Nucleotide monophosphate (NMP) kinases catalyse the phosphorylation of canonical nucleotides to the corresponding diphosphate using ATP as a phosphate donor . The bacteriophage T4 deoxynucleotide monophosphate (DNMP) kinases are unique in their ability to recognise three structurally dissimilar mononucleotides: dGMP, dTMP and 5'-hydroxymethyl-dCMP. The broad specificity is thought to result from the selective pressure for efficient DNA precursor synthesis in phage infected cells.

This superfamily represents a predominantly α-helical domain found in phage DNMP kinases.
TGS-like domain superfamily (TGS-like_dom_sf)
Type: Homologous_superfamily

This superfamily represents an α-helical TGS-like domain, which is found in the GTP1/OBG family which function as GTPases and ATPases .
3-phosphoshikimate 1-carboxyvinyltransferase, conserved site (EPSP_synthase_CS)
Type: Conserved_site

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 and 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 weed killers and antimicrobial drug development.

This entry represents two conserved regions as signature patterns. The first pattern corresponds to a region that is part of the active site and which is also important for the resistance to glyphosate . The second pattern 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.
Eukaryotic translation initiation factor 3-like domain superfamily (eIF3-like_dom_sf)
Type: Homologous_superfamily

At least eleven different protein factors are involved in initiation of protein synthesis in eukaryotes. Binding of initiator tRNA and mRNA to the 40S subunit requires the presence of the translation initiation factors eIF-2 and eIF-3, with eIF-3 being particularly important for 80S ribosome dissociation and mRNA binding. eIF-3 is the most complex translation inititation factor, consisting of about 13 putative subunits and having a molecular weight of between 550 - 700kDa in mammalian cells. Subunits are designated eIF-3a - eIF-3m; the large number of subunits means that the interactions between the individual subunits that make up the eIF-3 complex are complex and varied.
Nicotinate-nucleotide-dimethylbenzimidazole phosphoribosyltransferase, N-terminal (Nict_dMeBzImd_PRibTrfase_N)
Type: Homologous_superfamily

Nicotinate mononucleotide (NaMN):5,6-dimethylbenzimidazole (DMB) phosphoribosyltransferase (CobT) plays a central role in the synthesis of alpha-ribazole-5'-phosphate, an intermediate for the lower ligand of cobalamin . It is one of the enzymes of the anaerobic pathway of cobalamin biosynthesis, and one of the four proteins (CobU, CobT, CobC, and CobS) involved in the synthesis of the lower ligand and the assembly of the nucleotide loop .

Vitamin B
12
(cobalamin) is used as a cofactor in a number of enzyme-catalysed reactions in bacteria, archaea and eukaryotes . The biosynthetic pathway to adenosylcobalamin from its five-carbon precursor, 5-aminolaevulinic acid, can be divided into three sections: (1) the biosynthesis of uroporphyrinogen III from 5-aminolaevulinic acid; (2) the conversion of uroporphyrinogen III into the ring-contracted, deacylated intermediate precorrin 6 or cobalt-precorrin 6; and (3) the transformation of this intermediate to form adenosylcobalamin . Cobalamin is synthesised by bacteria and archaea via two alternative routes that differ primarily in the steps of section 2 that lead to the contraction of the macrocycle and excision of the extruded carbon molecule (and its attached methyl group) . One pathway (exemplified by Pseudomonas denitrificans) incorporates molecular oxygen into the macrocycle as a prerequisite to ring contraction, and has consequently been termed the aerobic pathway. The alternative, anaerobic, route (exemplified by Salmonella typhimurium) takes advantage of a chelated cobalt ion, in the absence of oxygen, to set the stage for ring contraction .

This superfamily represents the α-helical structural domain found at the N terminus of these proteins.