SII-SWORD/CoKE huggingface dataset:
Phage late-transcription coactivator superfamily (Trans_coact_sf)
Type: Homologous_superfamily

This superfamily represents a domain from proteins found in Caudovirales. It is a late-transcription coactivator which interacts with the host RNA polymerase forming a part of the initiation complex .
DsrC-like protein, C-terminal domain (DsrC-like_C)
Type: Homologous_superfamily

This superfamily includes TusE, a partner to TusBCD in a sulphur relay system for 2-thiouridine biosynthesis, a tRNA base modification process . Other members are DsrC , a functionally similar protein in species where the sulphur relay system exists primarily for sulphur metabolism , rather than tRNA base modification. Some members of this superfamily are known explicitly as the gamma subunit of sulphite reductases.

This superfamily represents the C-terminal domain found in DsrC and TusE proteins. It consists of 4 α helices.
TraM, DNA-binding domain (TraM_DNA-bd)
Type: Homologous_superfamily

This superfamily represents the TraM protein. TraM is a DNA-binding protein, encoded by plasmid DNA. TraM forms active tetramers to bridge the origin of transfer of the plasmid (oriT) to a TraD pore (a coupling protein) . As such, TraM is essential for conjugative transfer of DNA between bacteria.

Structurally, the DNA binding domain of the TraM protein is globular and dominantly helical .
Mycoplasma arthritidis-derived mitogen, C-terminal (M_arthritidis-der_mitogen_C)
Type: Homologous_superfamily

Mycoplasma arthritidis-derived mitogen (MA-Mit) adopts a completely α-helical structure consisting of ten α helices arranged in two orthogonal bundles. MA-Mit is a superantigen that can activate large fractions of T cells bearing particular TCR V-beta elements. Two MA-Mit molecules form an asymmetric dimer and cross-link two MHC antigens to form a dimerised MA-Mit-MHC complex .

This superfamily represents the C-terminal domain found in Mycoplasma arthritidis-derived mitogen.
KorB DNA-binding domain (KorB_DNA-db)
Type: Homologous_superfamily

This superfamily represents the KorB DNA-binding domain. The KorB protein of the broad-host-range plasmid RP4 acts as a multifunctional regulator of plasmid housekeeping genes, including those responsible for replication, maintenance and conjugation. KorB functions as the ParB analog of the plasmid's partitioning system . Structurally, the KorB consists of eight helices, two of which belong to a predicted helix-turn-helix motif .
Crisp-like domain (Crisp-like_dom)
Type: Homologous_superfamily

This superfamily represents a domain found in Cysteine-rich venom proteins or Cysteine-rich secretory proteins (Crisp). It is found in the mammalian reproductive tract and the venom of reptiles, and has been shown to regulate ryanodine receptor Ca2+ signalling . It contains 10 conserved cysteines which are all involved in disulphide bonds and is structurally related to the ion channel inhibitor toxins BgK and ShK .
Lysine tRNA ligase, stem contact fold domain (Lys-tRNA-ligase_SC_fold)
Type: Homologous_superfamily

Lysine-tRNA ligase (also knowns as lysyl-tRNA synthetase) (

) is an alpha 2 homodimer that belong to both class I and class II. In eubacteria and eukaryota lysine-tRNA ligases belong to class II in the same family as aspartate tRNA ligase. The class Ic lysine-tRNA ligase family is present in archaea and in a number of bacterial groups that include the alphaproteobacteria and spirochaetes. A refined crystal structures shows that the active site of lysU is shaped to position the substrates for the nucleophilic attack of the lysine carboxylate on the ATP alpha-phosphate. No residues are directly involved in catalysis, but a number of highly conserved amino acids and three metal ions coordinate the substrates and stabilise the pentavalent transition state. A loop close to the catalytic pocket, disordered in the lysine-bound structure, becomes ordered upon adenine binding .

The structure of LysRS-I is composed of 5 domains: a Rossmann-fold domain (domain 1), a helical insertion (Ins 1), a CP domain (domain 2), a SC-fold domain (domain 3) an α-helix bundle-like domain (domain 4) and an α-helix cage domain (domain 5).

This entry represents the stem contact fold (SC-fold) domain found in Lysine tRNA ligase.
ATP synthase, F1 beta subunit superfamily (ATP_synt_F1_beta_sf)
Type: Homologous_superfamily

This superfamily includes the F1 beta subunit of ATP synthase.
F-type ATPases have 2 components, CF1 - the catalytic core - and CF0 - the membrane proton channel. CF1 has five subunits: alpha3, beta3, gamma1, delta1, epsilon1. CF0 has three main subunits: a, b and c.

The NMR solution structure of the protein in SDS micelles was found to contain two helices, an N-terminal amphipathic α-helix and a C-terminal α-helix separated by a large unstructured internal domain. The N-terminal α-helix is the Tom20 receptor binding site whereas the C-terminal α-helix is located upstream of the mitochondrial processing peptidase cleavage site .
RNA 2'-phosphotransferase, N-terminal domain (RNA_2'-PTrans_N)
Type: Homologous_superfamily

The structure of the 2'-phosphotransferase contains two globular domains (N and C-domains), which form a cleft in the centre. The N-domain has the winged helix motif, a subfamily of the helix-turn-helix family, which is shared by many DNA-binding proteins. The C-terminal domain superimposes well on the NAD-binding fold of bacterial (diphtheria) toxins, which catalyze the transfer of ADP ribose from NAD to target proteins, indicating that the mode of NAD binding by the 2'-phosphotransferase could be similar to that of the bacterial toxins .

This superfamily represents the N-terminal domain found in RNA 2'-phosphotransferase.
RNA 2'-phosphotransferase, C-terminal domain (RNA_2'-PTrans_C)
Type: Homologous_superfamily

The structure of the 2'-phosphotransferase contains two globular domains (N and C-domains), which form a cleft in the centre. The N-domain has the winged helix motif, a subfamily of the helix-turn-helix family, which is shared by many DNA-binding proteins. The C-terminal domain superimposes well on the NAD-binding fold of bacterial (diphtheria) toxins, which catalyze the transfer of ADP ribose from NAD to target proteins, indicating that the mode of NAD binding by the 2'-phosphotransferase could be similar to that of the bacterial toxins .

This superfamily represents the C-terminal domain found in RNA 2'-phosphotransferase.
CST complex subunit Stn1, wHTH1 motif superfamily (CST_Stn1_wHTH1_sf)
Type: Homologous_superfamily

Stn1 is a component of the CST complex, a complex that binds to single-stranded DNA and is required to protect telomeres from DNA degradation. The CST complex binds single-stranded DNA with high affinity in a sequence-independent manner, while isolated subunits bind DNA with low affinity by themselves. In addition to telomere protection, the CST complex has probably a more general role in DNA metabolism at non-telomeric sites .

The C-terminal domain of Stn1 has two winged helix-turn-helix (wHTH) motifs, wHTH1 and wHTH2. This superfamily represents the wHTH1 motif, which is structurally similar to that in RPA32 with an additional large insertion between helices α2 and α3, unique to Stn1 . This additional wHTH1 motif may allow interaction with a different set of proteins that function at telomeres such as Ctc1 .
Alkaline phosphatase, crown domain (Ap_crown)
Type: Homologous_superfamily

This superfamily represents the alkaline phosphatases (AP) crown domain. AP are metalloenzymes that exist as a dimer, each monomer binding metal ions, generally zinc and magnesium. The crown domain has a variable size across different APs and its role is to connect the two subunits .
Methyltransferase, alpha-helical capping domain (MeTrfase_capping)
Type: Homologous_superfamily

This superfamily represents the α-helical capping domain found in various methyltransferases, such as fatty acid O-methyltransferase (FAMT), salicylic acid carboxyl methyltransferase (SAMT), xanthosine (XR) methyltransferase (XMT), and 1,7-dimethylxanthine methyltransferase (DXMT). The capping domain is formed of α-helices and contains a binding cavity that accommodates fatty acid substrates with acyl chain lengths up to C12. This domain establishes specificity for the hydrophobic part of the substrate and is responsible for the substrate binding .
DNA polymerase family B, thumb domain (DNA_pol_B_thumb)
Type: Homologous_superfamily

DNA is the biological information that instructs cells how to exist in an ordered fashion: accurate replication is thus one of the most important events in the life cycle of a cell. This function is performed by DNA- directed DNA-polymerases

) by adding nucleotide triphosphate (dNTP) residues to the 5'-end of the growing chain of DNA, using a complementary DNA chain as a template. Small RNA molecules are generally used as primers for chain elongation, although terminal proteins may also be used for the de novo synthesis of a DNA chain. Even though there are 2 different methods of priming, these are mediated by 2 very similar polymerases classes, A and B, with similar methods of chain elongation.
A number of DNA polymerases have been grouped under the designation of DNA polymerase family B. Six regions of similarity (numbered from I to VI) are found in all or a subset of the B family polymerases. The most conserved region (I) includes a conserved tetrapeptide with two aspartate residues. Its function is not yet known, however, it has been suggested that it may be involved in binding a magnesium ion. All sequences in the B family contain a characteristic DTDS motif, and possess many functional domains, including a 5'-3' elongation domain, a 3'-5' exonuclease domain , a DNA binding domain, and binding domains for both dNTP's and pyrophosphate .

This superfamily represents the thumb domain found at the C-terminal of the DNA polymerase family B proteins.
Oligoendopeptidase F, C-terminal domain (OligoPept_F_C)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain found in the Thimet oligopeptidase family, large family of mainly bacterial oligopeptidases that cleave medium sized peptides.
Peptidase M13, domain 2 (Peptidase_M13_dom_2)
Type: Homologous_superfamily

This superfamily represents the cytoplasmic domain (domain 2) found in M13 peptidases. These proteins consist of a short N-terminal cytoplasmic domain, a single transmembrane helix, and a larger C-terminal extracellular domain containing the active site. The cytoplasmic domain contains a conformationally-restrained octapeptide, which is thought to act as a stop transfer sequence that prevents proteolysis and secretion .
tRNA nucleotidyltransferase, domain 2 (CCA_tRNA_nucleotrans_2)
Type: Homologous_superfamily

This superfamily comprises a domain consisting of a five helical bundle core. It is predominantly found in Archaeal tRNA nucleotidyltransferases, following the catalytic nucleotidyltransferase domain .
Ska2, N-terminal (Ska2_N)
Type: Domain

This entry represents the N-terminal domain of Ska2.

Spindle and kinetochore-associated protein 2 (Ska2) is a component of the SKA1 complex (consists of Ska1, Ska2, and Ska3/Rama1), a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation . It is required for timely anaphase onset during mitosis, when chromosomes undergo bipolar attachment on spindle microtubules leading to silencing of the spindle checkpoint . The SKA1 complex is a direct component of the kinetochore-microtubule interface and directly associates with microtubules as oligomeric assemblies. The complex facilitates the processive movement of microspheres along a microtubule in a depolymerisation-coupled manner. In the complex, it is required for SKA1 localisation .
Pseudouridine synthase, RsuA/RluB/E/F, catalytic domain (PsdUridine_s_RsuA/RluB/E/F_cat)
Type: Homologous_superfamily

Pseudouridine synthases catalyse the isomerisation of uridine to pseudouridine (Psi) in a variety of RNA molecules, and may function as RNA chaperones. Pseudouridine is the most abundant modified nucleotide found in all cellular RNAs. There are four distinct families of pseudouridine synthases that share no global sequence similarity, but which do share the same fold of their catalytic domain(s) and uracil-binding site and are descended from a common molecular ancestor. The catalytic domain consists of two subdomains, each of which has an α+β structure that has some similarity to the ferredoxin-like fold (note: some pseudouridine synthases contain additional domains). The active site is the most conserved structural region of the superfamily and is located between the two homologous domains. These families are :

Pseudouridine synthase I, TruA.

Pseudouridine synthase II, TruB, which contains and additional C-terminal PUA domain.

Pseudouridine synthase RsuA. RluB, RluE and RluF are also part of this family.

Pseudouridine synthase RluA. TruC, RluC and RluD belong to this family.

Pseudouridine synthase TruD, which has a natural circular permutation in the catalytic domain, as well as an insertion of a family-specific α+β subdomain.

This entry represents the C-terminal region of the catalytic domain found in pseudouridine synthases from the RsuA family, including: RsuA (acts on small ribosomal subunit), RluB, RluE and RluF (act on large ribosomal subunit) .
Type II secretion system GspF domain superfamily (T2SS_GspF_sf)
Type: Homologous_superfamily

This superfamily consists of bacterial proteins involved in a general secretion pathway (GSP) for the export of proteins (also called the type II pathway) . These are proteins of about 400 amino acids that are highly hydrophobic and which are thought to be integral protein of the inner membrane. This domain consists of a bundle of six anti-parallel helices and has a novel fold . Proteins with this domain form a platform for the type II secretion machinery, as well as the type IV pili and the archaeal flagellae .
Sulfatase-modifying factor enzyme superfamily (SUMF_sf)
Type: Homologous_superfamily

This superfamily represents a domain is found in sulfatase-modifying factors (SUMFs) and Chlamydia serine/threonine-protein kinase pkn1 . It is also found in iron(II)-dependent oxidoreductase from Mycobacterium .
Dihydroxy-acid dehydratase, C-terminal (Dihydro-acid_dehy_C)
Type: Homologous_superfamily

Two dehydratases, dihydroxy-acid dehydratase (

) (gene ilvD or ILV3) and 6-phosphogluconate dehydratase (

) (gene edd) have been shown to be evolutionary related . Dihydroxy-acid dehydratase catalyses the fourth step in the biosynthesis of isoleucine and valine, the dehydratation of 2,3-dihydroxy-isovaleic acid into alpha-ketoisovaleric acid. 6-Phosphogluconate dehydratase catalyses the first step in the Entner-Doudoroff pathway, the dehydratation of 6-phospho-D-gluconate into 6-phospho-2-dehydro-3-deoxy-D-gluconate. Another protein containing this signature is Escherichia coli YjhG, which has been identified as a D-xylonate dehydratase .
Aminopeptidase N-like , N-terminal domain superfamliy (Aminopeptidase_N-like_N_sf)
Type: Homologous_superfamily

Aminopeptidase N from Escherichia coli is a broad specificity zinc exopeptidase belonging to aminopeptidase clan MA, family M1. The enzyme is composed of four domains: an N-terminal beta-domain, a catalytic domain, a middle beta-domain and a C-terminal alpha-domain .

This superfamily represents the N-terminal domain found in aminopeptidases and related proteins.
Taurine dioxygenase TauD-like superfamily (TauD-like_sf)
Type: Homologous_superfamily

This domain is found in Taurine dioxygenase (TauD) and related proteins. The Escherichia coli tauD gene is required for the utilisation of taurine (2-aminoethanesulphonic acid) as a sulphur source and is expressed only under conditions of sulphate starvation. TauD is an alpha-ketoglutarate-dependent dioxygenase catalysing the oxygenolytic release of sulphite from taurine .

This domain is also found in Glutarate 2-hydroxylase. This enzyme acts as an alpha-ketoglutarate-dependent dioxygenase catalyzing hydroxylation of glutarate (GA) to L-2-hydroxyglutarate (L2HG).

This domain is also found in gamma-butyrobetaine hydroxylase (GBBH), the enzyme responsible for the biosynthesis of L-carnitine, a key molecule of fatty acid metabolism. The GBBH monomer consists of this catalytic double-stranded β-helix (DBSH) domain, which is found in all 2-ketoglutarate (2KG) oxygenases, and a smaller N-terminal domain .
ANL, N-terminal domain (ANL_N_sf)
Type: Homologous_superfamily

This superfamily comprises structural domains found at the N terminus of various ligases from the ANL superfamily. The name ANL derives from three of the subfamilies - Acyl-CoA synthetases, the adenylation domains of the modular non-ribosomal peptide synthetases (NRPSs), and the luciferase enzymes. Members of this superfamily include luciferase, long chain fatty acid Co-A ligase, acetyl-CoA synthetase and various other closely-related synthetases as well as a plant auxin-responsive promoter family. These enzymes are involved in catalysing the initial adenylation of a carboxylate to form an acyl-AMP intermediate, followed by a second partial reaction, most commonly the formation of a thioester. These adenylating enzymes utilise a 140 degrees rotation of the C-terminal domain to adopt two distinct conformations that are used for the adenylation and thiolation reactions. Thus, by using two different conformations of the C-terminal domain, these enzymes perform two distinct steps of catalysis.

Luciferases are composed of a large N-terminal domain and a smaller C-terminal domain, which form a cleft. The active site of these enzymes is located at the interface between these two domains, with most active site residues located in the N-terminal domain, and two lysine residues in the C-terminal domain. The N-terminal domain is involved in catalysis, and the C-terminal domain is essential for luciferase activation during the catalytic reaction .

The overall structure of the N-terminal domain has been characterised in a fatty acyl-CoA ligase in M. tuberculosis, FA and fatty acyl-AMP ligase FAAL28. The N-terminal domain of FA consists of three subdomains: subdomains A and B form α+β topology, which pack together to form a five-layered α-β-α-β-α tertiary structure. The third subdomain C folds into a distorted β-barrel topology. In FAAL28, the C-subdomain presents an insertion between β-strands 1 and 2. A hydrophobic interaction was identified at the interface of insertion and N-terminal domain, and it was suggested to play a fundamental role in anchoring the insertion motif and arresting the acyl-CoA catalysis .

The Mycobacterium tuberculosis fatty acyl-CoA synthetase (ACS) FadD13 is a peripheral membrane protein essential for virulence and intracellular growth of the pathogen. FadD13 was identified to play a central role in lipid metabolism, and therefore would be a possible drug target. FadD13 comprises an N- and a C-terminal domain. The N-terminal domain folds into an α+β topology and can be further divided into two subdomains. The CoA binding site in ACS proteins is formed in the junction between the domains upon a 140 degrees rotation of the C-terminal domain after the initial adenylation step .
Bordetella uptake gene, domain 1 (Bug_dom1)
Type: Homologous_superfamily

Bug, for Boardetella Uptake Gene, proteins are a large family of periplasmic solute-binding proteins abundant in beta-proteobacteria. They adopt a characteristic Venus flytrap fold with two globular domains bisected by a ligand-binding cleft . These proteins are specific for carboxylated solutes and show a characteristic mode of binding which involves two highly conserved β-strand-β-turn-α-helix motifs originating from each domain. Structural domains comprising this superfamily share the structure of domain 1, involved in ligand recognition. However, stabilization of the closed conformation requires proper interactions to be established with domain 2, and thus domain 2 discriminates between productively and non-productively bound ligands .
Signal recognition particle SRP54, N-terminal domain superfamily (SRP54_N_sf)
Type: Homologous_superfamily

The signal recognition particle (SRP) is a ribonucleoprotein that mediates co-translational targeting of nascent proteins to the membrane. SRP54 of the signal recognition particle has a three-domain structure: an N-terminal helical bundle domain, a GTPase domain, and the M-domain that binds the 7s RNA and also binds the signal sequence. The extreme C-terminal region is glycine-rich and lower in complexity and poorly conserved between species.

This superfamily describes the N-terminal domain, a four-helical bundle, that has a key function in regulating the nucleotide-binding interactions of the GTPase domain. The SRP54 component is a GTP-binding protein that interacts with the signal sequence when it emerges from the ribosome .
RNA polymerase Rpb1, domain 3 superfamily (RNA_pol_Rpb1_3_sf)
Type: Homologous_superfamily

This superfamily represents the domain 3 found in RNA polymerase Ppb1, an enzyme which catalyses RNA synthesis. This domain is a pore domain, thought to be a channel through which nucleotides enter the active site and/or through which the 3' end of RNA is extruded. The latter is based on the fact that the 3' end of RNA is located very close to this domain .
Serine-tRNA synthetase, type1, N-terminal domain superfamily (SerRS_1_N_sf)
Type: Homologous_superfamily

The seryl-tRNA synthetase (SerRS) is a homodimeric enzyme that belongs to class II tRNA synthetases. SerRS catalyses the aminoacylation reaction that charges serine onto its cognate tRNA for protein synthesis. Each monomer is comprised of two domains: an N-terminal tRNA-binding domain and a catalytic domain composed of seven-stranded anti-parallel β-sheet .

This entry represents the N-terminal domain of Serine-tRNA synthetase, which consists of two helices in a long α-hairpin and corresponds to the tRNA binding domain. Serine-tRNA synthetase (

) exists as monomer and belongs to class IIa aminoacyl-tRNA synthetase .
Polyketide synthase, dehydratase domain superfamily (PKS_dehydratase_sf)
Type: Homologous_superfamily

This superfamily represents the dehydratase (DH) domain found in polyketide synthases, which are in fact megasynthases comprised of different modules. Each module is composed of several enzymes which together act a ketide unit to the growing polyketide chain. DH is involved in the generation, through an elimination reaction, a double bond in this process . The structure of the DH domain is described as a hotdog fold with the α-helices representing the sausages and the β-sheet representing the bun.