SII-SWORD/CoKE huggingface dataset:
RNA 3'-terminal phosphate cyclase domain superfamily (RNA3'_phos_cyclase_dom_sf)
Type: Homologous_superfamily

RNA cyclases are a family of RNA-modifying enzymes that are conserved in eukaryotes, bacteria and archaea. Type 1 RNA 3'-terminal phosphate cyclases (

) catalyse the conversion of 3'-phosphate to a 2',3'-cyclic phosphodiester at the end of RNA:

ATP + RNA 3'-terminal-phosphate = AMP + diphosphate + RNA terminal-2',3'-cyclic-phosphate

The physiological function of the cyclase is not known, but the enzyme could be involved in the maintenance of cyclic ends in tRNA splicing intermediates or in the cyclisation of the 3' end of U6 snRNA .

A second subfamily of RNA 3'-terminal phosphate cyclases (type 2) that do not have cyclase activity have been identified in eukaryotes. They are localised to the nucleolus and are involved in ribosomal modification .

The crystal structure of RNA 3'-terminal phosphate cyclase shows that each molecule consists of two domains. The larger domain contains three repeats of a folding unit comprising two parallel α helices and a four-stranded β sheet; this fold was previously identified in translation initiation factor 3 (IF3). The large domain is similar to one of the two domains of 5-enolpyruvylshikimate-3-phosphate synthase and UDP-N-acetylglucosamine enolpyruvyl transferase. The smaller domain uses a similar secondary structure element with different topology, observed in many other proteins such as thioredoxin . Although the active site of this enzyme has not been unambiguously assigned, it can be mapped to a region surrounding His309, an adenylate acceptor, in which a number of amino acids are highly conserved in the enzyme from different sources .
Cucumovirus coat protein, subunit A superfamily (Cucumovirus_coat_Asu_sf)
Type: Homologous_superfamily

Cucumoviruses are tripartite RNA plant viruses believed to share a close evolutionary relationship with Brome mosaic virus (BMV). The cucumoviruses include: Cucumber mosaic virus , Peanut stunt virus and Tomato aspermy virus . The viral coat proteins show a high degree of sequence similarity .

The core structure of cucumber mosaic virus (CMV) and chlorotic mottle virus (CCMV), both members of the Bromoviridae family, are highly homologous. In CCMV, the structures of the A, B, and C subunits are nearly identical except in their N termini. In contrast, the structures of two loops in subunit A of CMV differ from those in B and C . This entry represents the structural domain superfamily of subunit A of the cucumber mosaic virus and other cucumovirusus .
Histone deacetylase domain superfamily (His_deacetylse_dom_sf)
Type: Homologous_superfamily

This entry represents the structural domain superfamily found in histone deacetylases, acetoin utilisation proteins, and acetylpolyamine amidohydrolases. It consists of a 3-layer(α-β-α) sandwich.

Histone deacetylases (HDACs)

are a class of enzymes that remove acetyl groups from N(6)-acetyl-lysine residues on histones. This process plays a critical role in transcription regulation, as HDACs facilitate tighter wrapping of DNA around histones. DNA expression is regulated in part by the balance between acetylation and deacetylation. The reaction catalyzed by HDACs is the reverse of

, which transfers acetyl groups to histones. In general, HDACs suppress gene expression because the removal of acetyl groups from the ε-amino group of lysine side chains at the N-terminal of histones restores the positive charge of lysine residues. This stabilization strengthens histone-DNA interactions and prevents transcription factors from binding to promoter elements . HDACs, along with acetoin utilization proteins and acetylpolyamine amidohydrolases, belong to an ancient protein superfamily .
HDAC can be divided by different classes :

Class I:
Includes HDAC1, HDAC2, HDAC3, and HDAC8. Generally nuclear and involved in transcriptional repression.

Class II:
Includes HDAC4, HDAC5, HDAC6, HDAC7, HDAC9, and HDAC10. Can shuttle between the nucleus and cytoplasm and are involved in diverse cellular processes. Subdivided into IIa (HDAC4, 5, 7, 9) and IIb (HDAC6, 10).

Class III:
Sirtuins (SIRT1-7 in mammals). NAD+-dependent deacetylases with different enzymatic mechanisms, involved in aging, metabolism, and stress response. Often considered a separate family.

Class IV:
Includes HDAC11. Has characteristics of both Class I and II.
von Hippel-Lindau disease tumour suppressor, alpha domain superfamily (VHL_alpha_dom_sf)
Type: Homologous_superfamily

von Hippel-Landau (pVHL) protein, the gene product of VHL, is a critical regulator of the ubiquitous oxygen-sensing pathway. It is conserved throughout evolution, as its homologues are found in organisms ranging from mammals to Drosophila and Caenorhabditis. pVHL acts as the substrate recognition component of an E3 ubiquitin ligase complex. Several proteins have been identified as pVHL-binding proteins that are subject to ubiquitin-mediated proteolysis; the best characterised putative substrates are the alpha subunits of the hypoxia-inducible factor (HIF1alpha, HIF2alpha, and HIF3alpha). In addition to HIF degradation, pVHL has been implicated to be involved in HIF-independent cellular processes. Germline VHL mutations cause renal cell carcinomas, haemangioblastomas and pheochromocytomas in humans. pVHL can bind to and direct the proper deposition of fibronectin and collagen IV within the extracellular matrix. It works to stabilise microtubules and foster the maintenance of primary cilia. It also has been reported to promote the stabilization and activation of p53 in a HIF-independent manner and, in neuronal cells, promote apoptosis by down-regulation of Jun-B .

Von Hippel-Lindau disease tumour suppressor (VHL) has two domains: a roughly 100-residue N-terminal domain rich in β-sheet (beta domain) and a smaller α-helical domain (alpha domain), held together by two linkers and a polar interface. A large portion of the alpha domain surface, and a small portion of the beta domain interact with ElonginC. About half of the tumorigenic mutations map to the alpha domain and its residues that contact ElonginC. The remaining mutations map to the beta domain and, significantly, to a beta domain surface patch uninvolved in ElonginC binding. This suggests that two intact macromolecular binding sites may be required for the tumor suppressor effects of VHL .

This entry represents the alpha domain superfamily of VHL.
von Hippel-Lindau disease tumour suppressor, beta domain superfamily (VHL_beta_dom_sf)
Type: Homologous_superfamily

von Hippel-Landau (pVHL) protein, the gene product of VHL, is a critical regulator of the ubiquitous oxygen-sensing pathway. It is conserved throughout evolution, as its homologues are found in organisms ranging from mammals to Drosophila and Caenorhabditis. pVHL acts as the substrate recognition component of an E3 ubiquitin ligase complex. Several proteins have been identified as pVHL-binding proteins that are subject to ubiquitin-mediated proteolysis; the best characterised putative substrates are the alpha subunits of the hypoxia-inducible factor (HIF1alpha, HIF2alpha, and HIF3alpha). In addition to HIF degradation, pVHL has been implicated to be involved in HIF-independent cellular processes. Germline VHL mutations cause renal cell carcinomas, haemangioblastomas and pheochromocytomas in humans. pVHL can bind to and direct the proper deposition of fibronectin and collagen IV within the extracellular matrix. It works to stabilise microtubules and foster the maintenance of primary cilia. It also has been reported to promote the stabilization and activation of p53 in a HIF-independent manner and, in neuronal cells, promote apoptosis by down-regulation of Jun-B .

Von Hippel-Lindau disease tumour suppressor (VHL) has two domains: a roughly 100-residue N-terminal domain rich in β-sheet (beta domain) and a smaller α-helical domain (alpha domain), held together by two linkers and a polar interface. A large portion of the alpha domain surface, and a small portion of the beta domain interact with ElonginC. About half of the tumorigenic mutations map to the alpha domain and its residues that contact ElonginC. The remaining mutations map to the beta domain and, significantly, to a beta domain surface patch uninvolved in ElonginC binding. This suggests that two intact macromolecular binding sites may be required for the tumor suppressor effects of VHL .

This entry represents the beta domain superfamily of VHL.
NDT80 DNA-binding domain superfamily (NDT80_DNA-bd_dom_sf)
Type: Homologous_superfamily

The NDT80 DNA-binding domain superfamily is found in the following proteins, which might all be involved in sensing nutritional status :

Yeast meiosis-specific transcription factor NDT80, the key transcription factor that ultimately allows the continuation of meiosis after the successful completion of recombination.

Emericella nidulans phoG (xprG), a transcriptional activator involved in the response to nutrient limitation.

Emericella nidulans putative uncharacterised protein AN6015.2.

Neurospora crassa transcription factor vib-1, involved in the control of heterokaryon incompatibility.

Neurospora crassa related to acid phosphatase NCU04729.

Neurospora crassa related to meiosis-specific protein NDT80 NCU09915.

The proteolytically resistant core NDT80 DNA-binding domain reveals a central β-sandwich characteristic of an s-type Ig fold. The β-sandwich contains a three-stranded sheet composed of strands a, b and e, packed against a four-stranded sheet composed of strands c', c, f and g. Each sheet of the β-sandwich contains an additional β-strand, as well as a variety of peripheral secondary structure elements. The NDT80 DNA-binding domain contains an N-terminal extension, which consists of a β-hairpin and a loop .
4'-phosphopantetheinyl transferase domain superfamily (4-PPantetheinyl_Trfase_dom_sf)
Type: Homologous_superfamily

The 4'-phosphopantetheinyl transferase domain superfamily of proteins transfer the 4'-phosphopantetheine (4'-PP) moiety from coenzyme A (CoA) to the invariant serine of pp-binding. This post-translational modification renders holo-ACP capable of acyl group activation via thioesterification of the cysteamine thiol of 4'-PP . This superfamily consists of two subtypes: The ACPS type such as ACPS_ECOLI and the Sfp type such as SFP_BACSU. The structure of the Sfp type is known , which shows the active site accommodates a magnesium ion. The most highly conserved regions of the alignment are involved in binding the magnesium ion.
Peptidase M1, alanyl aminopeptidase, C-terminal domain superfamily (Peptidase_M1_pepN_C_sf)
Type: Homologous_superfamily

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .

This domain superfamily, which contains a conserved FSAPV sequence motif, is found in the C-terminal of alanyl aminopeptidases that belong to MEROPS peptidase family M1 (aminopeptidase N, clan MA).
Smad anchor for receptor activation, Smad-binding domain superfamily (SARA_Smad-bd_sf)
Type: Homologous_superfamily

Smad proteins mediate transforming growth factor-beta (TGF-beta) signaling from the transmembrane serine-threonine receptor kinases to the nucleus. SARA (Smad anchor for receptor activation) recruits Smad2 to the TGF-beta receptors for phosphorylation .

This entry represents the Smad-binding domain (SBD) superfamily of SARA. This domain consists of a rigid coil, an α helix, and a β strand, and interacts with Smad2 .
Colicin/pyocin, DNase domain superfamily (Colicin/pyocin_DNase_dom_sf)
Type: Homologous_superfamily

This entry represents the DNase domain found in some colicin/pyocin bacteriocins, including colicin E2, E7, E9 and pyocin S1 and S2. In colicin E7, this domain has been described as a novel α/β fold containing a Zn2+ ion binding site .

Bacteriocins are protein antibiotics that kill bacteria closely related to the producing species. Colicins are a subgroup of bacteriocins that are produced by and target Escherichia coli. The lethal action of most colicins is exerted either by formation of a pore in the cytoplasmic membrane of the target cell, or by an enzymatic nuclease digestion mechanism . S-type pyocins cause cell death by DNA breakdown due to its endonuclease activity .
Large ribosomal subunit protein bL28 superfamily (Ribosomal_bL28_sf)
Type: Homologous_superfamily

This entry consists of large ribosomal subunit protein bL28 from bacteria and eukaryotes, including the mitochondrial bL28m (also known as 39S ribosomal protein L28, MRLP28) from vertebrates, mitochondrial bL28m (also known as 54S ribosomal protein L24, MRLP24) from yeast and bL28c (also known as 50S ribosomal protein L28, RPL28) from plants. They are components of the mitochondrial or non-mitochondrial large ribosomal subunits.

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
[NiFe]-hydrogenase, small subunit, C-terminal domain superfamily (NiFe-Hase_small_C_sf)
Type: Homologous_superfamily

This entry represents the C-terminal domain superfamily of periplasmic [NiFe] hydrogenase small subunit, hydrogenase-1 small chain and uptake hydrogenase small subunit.

Hydrogenases catalyse the reversible oxidation of molecular hydrogen and play a vital role in anaerobic metabolism. Metal-containing hydrogenases are subdivided into three classes: Fe ('iron only') hydrogenases; Ni-Fe hydrogenases; and Ni-Fe-Se hydrogenases . Hydrogen oxidation is coupled to the reduction of electron acceptors (such as oxygen, nitrate, sulphate, carbon dioxide and fumarate), whereas proton reduction (hydrogen evolution) is essential in pyruvate fermentation or in the disposal of excess electrons.

The Ni-Fe hydrogenases, when isolated, are found to catalyse both hydrogen evolution and uptake, with low-potential multihaem cytochromes, such as cytochrome c3, acting as either electron donors or acceptors, depending on their oxidation state. Both periplasmic (soluble) and membrane-bound hydrogenases are known.

The Ni-Fe hydrogenases are heterodimeric proteins consisting of small (S) and large (L) subunits. The small subunit contains three iron-sulphur clusters (two [4Fe-4S] and one [3Fe-4S]); the large subunit contains a nickel ion . Small subunits of membrane-bound Ni-Fe hydrogenases contain a C-terminal domain of about 40 residues that is absent in periplasmic forms.
Protective antigen, heptamerisation domain superfamily (PA_heptamer_dom_sf)
Type: Homologous_superfamily

Protective antigen (PA) is the central component of the three-part protein toxin secreted by Bacillus anthracis, the organism responsible for anthrax. Homologues of PA have been found in several spore-forming Gram-positive bacteria, and share the ability to translocate toxic enzymes into the host cytosol.The PA monomer is organised mainly into antiparallel β-sheets and has four domains: an N-terminal domain (domain 1) containing two calcium ions and the cleavage site for activating proteases; a heptamerisation domain (domain 2) containing a large flexible loop implicated in membrane insertion; a small domain of unknown function (domain 3); and a carboxy-terminal receptor-binding domain (domain 4) .

This entry represents the heptamerisation domain superfamily of the protective antigen.
Histone-like protein H-NS, C-terminal domain superfamily (H-NS_C_dom_sf)
Type: Homologous_superfamily

This entry represents the C-terminal domain superfamily of the H-NS DNA binding protein. It is composed of an antiparallel β-sheet, an α-helix and a 3 (10)-helix which form a hydrophobic core, stabilising the whole structure. This domain has been found to bind to DNA .
Alpha-ketoglutarate-dependent dioxygenase AlkB-like superfamily (AlkB-like_sf)
Type: Homologous_superfamily

This superfamily brings together catalytic domains found in Alpha-ketoglutarate-dependent dioxygenase AlkB-like DNA/RNA demethylases.

AlkB is a DNA repair enzyme that removes methyl adducts and some larger alkylation lesions from endocyclic positions on purine and pyrimidine bases. It is a dioxygenase that requires molecular oxygen, alpha-ketoglutarate and iron .

The catalytic core of AlkB is homologous to other Fe-2OG dioxygenases . Two discrete global conformations have been observed for AlkB, differing in accessibility of a putative oxygen-diffusion tunnel .
L-asparaginase, N-terminal domain superfamily (L-asparaginase_N_sf)
Type: Homologous_superfamily

This entry represents the N-terminal domain superfamily of the L-asparaginase. Each monomer of L-asparaginase is arranged into two easily identifiable domains, the larger N-terminal domain and the smaller C-terminal domain, connected by a linker consisting of approximately 20 residues . The N-terminal domain covers two conserved threonine residues, which have been shown to play a catalytic role . One of them is located in the N-terminal extremity while the second one is located at the end of the first third of the sequence.

Asparaginase is found in various plant, animal and bacterial cells, catalyses the deamination of asparagine to yield aspartic acid and an ammonium ion, resulting in a depletion of free circulatory asparagine in plasma . Glutaminase, a similar enzyme, catalyses the deaminination of glutamine to glutamic acid and an ammonium ion . Both asparaginase and glutaminase contain the domain represented in this entry.
Pyrimidine/purine nucleotide 5'-monophosphate nucleosidase PpnN-like superfamily (PpnN-like_sf)
Type: Homologous_superfamily

This domain can be found at the N terminus of pyrimidine/purine nucleotide 5'-monophosphate nucleosidase (PpnN, also known as YgdH) from bacteria. PpnN catalyses the hydrolysis of the N-glycosidic bond of diverse pyrimidine and purine nucleotide 5'-monophosphates, to form ribose 5-phosphate and the corresponding free base. It can use AMP, GMP, IMP, CMP, dTMP and UMP as substrates. This enzyme adopts a tetrameric configuration with allosteric (p)ppGpp binding sites located between subunits. The binding of this alarmone molecule, which play a role in the bacterial stringent response, gives rise to a large conformational change involving the terminal region that leads to the exposure of the catalytic pocket. The N-terminal
domain consists of a three-stranded anti-parallel β-sheet surrounded by α-helices .
YtpR-like superfamily (YtpR-like_sf)
Type: Homologous_superfamily

The function of this domain superfamily is not known. It is found in bacteria in association with a putative tRNA-binding domain (

).
Staphopain proregion superfamily (Staphopain_pro_sf)
Type: Homologous_superfamily

This domain superfamily corresponds to the proregion of the cysteine protease staphopain (MEROPS identifier C47.003). Like many papain type peptidases, staphopain is synthesised as an inactive precursor and cleavage of the proregion is required for activation. This proregion has a half-barrel or barrel-sandwich hybrid fold. The proregion blocks the active site cleft of the mature enzyme on one side of the nucleophilic cysteine .
Like-Sm ribonucleoprotein, C-terminal domain superfamily (Lsm_C_sf)
Type: Homologous_superfamily

This domain superfamily is found at the C terminus of archaeal like-Sm (Lsm) proteins .
UDP-N-acetylglucosamine O-acyltransferase, C-terminal domain superfamily (Acetyltransf_C_sf)
Type: Homologous_superfamily

This entry represents the C-terminal domain superfamily of UDP-N-acetylglucosamine acyltransferase. This enzyme is a zinc-dependent enzyme that catalyses the deacetylation of UDP-3-O-((R)-3-hydroxymyristoyl)-N-acetylglucosamine to form UDP-3-O-(R-hydroxymyristoyl)glucosamine and acetate .
Threonine synthase, N-terminal domain superfamily (Thr_synth_N_sf)
Type: Homologous_superfamily

This domain superfamily is found at the N terminus of many threonine synthase enzymes . Threonine synthases catalyses the gamma-elimination of phosphate from L-phosphohomoserine and the beta-addition of water to produce L-threonine .
DNA-directed RNA polymerase, N-terminal domain superfamily (RNA_POL_N_sf)
Type: Homologous_superfamily

This entry represents the N-terminal domain superfamily of DNA-directed RNA polymerase. This domain has a role in interaction with regions of upstream promoter DNA and the nascent RNA chain, leading to the processivity of the enzyme . In order to make mRNA transcripts the RNA polymerase undergoes a transition from the initiation phase (which only makes short fragments of RNA) to an elongation phase. This domain undergoes a structural change in the transition from initiation to elongation phase. The structural change results in abolition of the promoter binding site, creation of a channel accommodating the heteroduplex in the active site, and formation of an exit tunnel which the RNA transcript passes through after peeling off the heteroduplex .
DNA polymerase, thumb domain superfamily (DNA_Pol_thumb_sf)
Type: Homologous_superfamily

The catalytic region of DNA polymerase beta is split into three domains. An N-terminal fingers domain, a central palm domain and a C-terminal thumb domain. This entry represents the thumb domain superfamily .
Semialdehyde dehydrogenase-like, C-terminal (Semialdehyde_DH-like_C)
Type: Homologous_superfamily

This entry represents the C-terminal domain superfamily of putative bacterial semialdehyde dehydrogenase proteins.