SII-SWORD/CoKE huggingface dataset:
Dodecin-like superfamily (Dodecin-like_sf)
Type: Homologous_superfamily

This entry represents proteins with a Dodecin topology. Dodecin flavoprotein is a small dodecameric flavin-binding protein from Halobacterium salinarium (Halobacterium halobium) that contains two flavins stacked in a single binding pocket between two tryptophan residues to form an aromatic tetrade . Dodecin binds riboflavin, although it appears to have a broad specificity for flavins. Lumichrome, a molecule associated with flavin metabolism, appears to be a ligand of dodecin, which could act as a waste-trapping device. The subunit assembly and the probable biological unit is a dodecamer .
Arginyl tRNA synthetase N-terminal domain superfamily (Arg-tRNA-synth_N_sf)
Type: Homologous_superfamily

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .

This domain superfamily is found at the N terminus of Arginyl tRNA synthetase, also called additional domain 1 (Add-1). It is about 140 residues long and it has been suggested to be involved in tRNA recognition .
YdfO-like superfamily (YdfO-like_sf)
Type: Homologous_superfamily

This superfamily consists of several hypothetical bacterial proteins of around 130 residues in length. The function of this superfamily is unknown.
Hemocyanin, N-terminal domain superfamily (Hemocyanin_N_sf)
Type: Homologous_superfamily

This entry represents the N-terminal domain of hemocyanin and hexamerin. This domain is composed of six helices arranged in a bundle fold where one central helix is surrounded by 5 others.

Crustacean and cheliceratan hemocyanins (oxygen-transport proteins) and insect hexamerins (storage proteins) are homologous gene products, although the latter do not bind oxygen .

Haemocyanins are found in the haemolymph of many invertebrates. They are divided into 2 main groups, arthropodan and molluscan. These have structurally similar oxygen-binding centres, which are similar to the oxygen-binding centre of tyrosinases, but their quaternary structures are arranged differently. The arthropodan proteins exist as hexamers comprising 3 heterogeneous subunits (a, b and c) and possess 1 oxygen-binding centre per subunit; and the molluscan proteins exist as cylindrical oligomers of 10 to 20 subunits and possess 7 or 8 oxygen-binding centres per subunit . Although the proteins have similar amino acid compositions, the only real similarity in their primary sequences is in the region corresponding to the second copper-binding domain, which also shows similarity to the copper-binding domain of tyrosinases.
TM1070-like superfamily (TM1070-like_sf)
Type: Homologous_superfamily

This superfamily consists of several hypothetical bacterial proteins of around 125 resides in length, including the hypothetical protein TM1070 from Thermotoga maritima, which has a β-sandwich structure with a jelly-roll fold. The function of these proteins is unknown.
YehR-like superfamily (YehR-like_sf)
Type: Homologous_superfamily

This superfamily consists of several hypothetical bacterial proteins of around 150 residues in length. Some members are described as putative lipoproteins but their function is unknown.
Bacterial OB-fold superfamily (BOBF_sf)
Type: Homologous_superfamily

Proteins in this entry have an OB-fold fold (oligonucleotide/oligosaccharide binding motif). Analysis of the predicted nucleotide-binding site of the OB-fold suggests that they lack nucleic acid-binding properties. They contain a predicted N-terminal signal peptide which indicates that they localise to the periplasm where they may function to bind proteins, small molecules, or other typical OB-fold ligands. As hypothesised for the distantly related OB-fold containing bacterial enterotoxins, the loss of nucleotide-binding function and the rapid evolution of the OB-fold ligand-binding site may be associated with the presence of members in mobile genetic elements and their potential role in bacterial pathogenicity .

Structurally, an OB-fold domain has a close or partly open barrel fold and a greek-key topology.
RraB-like superfamily (RraB-like_sf)
Type: Homologous_superfamily

This entry represents a domain found in regulator of ribonuclease activity B (RraB) protein. RraB regulates mRNA abundance by binding to RNaseE and inhibiting its endonucleolytic activity . A subset of these proteins are predicted to function as immunity proteins .
ComB-like superfamily (ComB-like_sf)
Type: Homologous_superfamily

2-phosphosulpholactate phosphatase (ComB;

) is a magnesium-dependent acid phosphatase that catalyzes the second step in coenzyme M (CoM; 2-mercaptoethanesulphonic acid) biosynthesis, namely, the hydrolysis of (2R)-2-phospho-3-sulpholactate to yield (2R)-3-sulpholactate and phosphate. CoM is an essential cofactor that acts as the terminal methyl carrier in methanogenesis . CoM has also a role in the bacterial pathway of aliphatic epoxide carboxylation . Homologues of ComB have been identified in all available cyanobacterial genome sequences and in genomes from phylogenetically diverse bacteria and archaea. However, many of these organisms lack homologues of other CoM biosynthetic genes.

ComB has a complex α/β topology. The monomer is composed of two domains thought to be related by a common ancestral gene, plus a C-terminal helical and β-hairpin region .
MOB kinase activator superfamily (MOB_kinase_act_sf)
Type: Homologous_superfamily

The MOB kinase activator superfamily includes MOB1, an essential Saccharomyces cerevisiae protein, identified from a two-hybrid screen, that binds Mps1p, a protein kinase essential for spindle pole body duplication and mitotic checkpoint regulation. Conditional alleles of MOB1 cause a late nuclear division arrest at restrictive temperature . This superfamily also includes the MOB-like protein phocein, an intracellular protein that interacts with striatin and may play a role in membrane trafficking . Structurally, domains in this superfamily have a bromodomain-like fold, which consists of four helices arranged as a bundle with a minor mirror variant of up-and-down topology; they also contain a zinc-binding site.
Ribonuclease E inhibitor RraA/RraA-like superfamily (RraA/RraA-like_sf)
Type: Homologous_superfamily

This entry represents the regulator of ribonuclease E activity A (RraA). These proteins contain a swivelling 3-layer β/β/α domain that appears to be mobile in most multi-domain proteins known to contain it. These proteins are structurally similar, and may have distant homology, to the phosphohistidine domain of pyruvate phosphate dikinase. The RraA fold is an ancient platform that has been adapted for a wide range of functions. RraA had been identified as a putative demethylmenaquinone methyltransferase and was annotated as MenG, but further analysis showed that RraA lacked the structural motifs usually required for methylases .
ADP-ribosylation/Crystallin J1 superfamily (Ribosyl_crysJ1_sf)
Type: Homologous_superfamily

This superfamily includes enzymes that perform ADP-ribosylations, such as ADP-ribosylarginine hydrolase

which cleaves ADP-ribose-L-arginine . The superfamily also includes dinitrogenase reductase activating glycohydrolase , and most surprisingly jellyfish crystallins , although these proteins appear to have lost the presumed active site residues.

ADP-ribosylglycohydrolase has a multihelical structure arranged in a bundle fold.
Vitelline membrane outer layer protein I (VOMI) superfamily (VOMI_sf)
Type: Homologous_superfamily

Vitelline membrane outer layer protein I (VMO-I) is one of the proteins found in the outer layer of the vitelline membrane of eggs. VMO-I, lysozyme, and VMO-II are bound tightly to ovomucin fibrils of the egg yolk membrane. The structure of VMO-I consists of three β-sheets forming Greek key motifs, which are related by an internal pseudo three-fold symmetry. It is a member of the β-prism-fold family and the structure of VOM-I has strong similarity to the structure of the delta-endotoxin, as well as a carbohydrate-binding site in the top region of the common fold . VMO-I has been shown to synthesize N-acetylchito-oligosaccharides from N-acetylglucosamine.
Cell division topological specificity factor MinE superfamily (MinE_sf)
Type: Homologous_superfamily

Cytokinesis needs to be regulated spatially in order to ensure that it occurs between the daughter genomes. In prokaryotes such as Escherichia coli, cytokinesis is initiated by FtsZ, a tubulin-like protein that assembles into a ring structure at the cell centre called the Z ring. A fundamental problem in prokaryotic cell biology is to understand how the midcell division site is identified. Two major negative regulatory systems are known to be involved in preventing Z-ring assembly at all sites except the midcell. One of these systems, called nucleoid occlusion, blocks Z-ring assembly in the area occupied by an unsegregated nucleoid until a critical stage in chromosome replication or segregation is reached. The other system consists of three proteins, MinC, MinD and MinE, which prevent assembly of Z rings in regions of the cell not covered by the nucleoid, such as the cell poles. MinC is an inhibitor of FtsZ polymerisation, resulting in the inhibition of Z ring assembly in the cell; MinD greatly enhances the inhibitory effects of MinC in vivo; and MinE antagonizes the effects of MinC and MinD .

MinE is a small bifunctional protein. The amino terminus of MinE is required to interact with MinD, while the carboxyl terminus is required for 'topological specificity' - that is, the ability of MinE to antagonise MinCD inhibition of Z rings at the midcell position but not at the poles . Structurally, MinE has dimer of α-β(2) motifs and two layers (alpha/beta).

This entry also includes plant MinE1 located in chloroplasts. AtMinE1 acts as a topological specificity factor during plastid division and specify plastid constriction sites .
BipD-like superfamily (BipD-like_sf)
Type: Homologous_superfamily

IpaD from Shigella flexneri and BipD from Burkholderia pseudomallei are two proteins that sit at the tip of the needle of type III secretion system and are essential for virulence . Their structures are highly homologous. They consist of a bundle of antiparallel α-helical segments with two small β-sheet regions .
Autotransporter beta-domain superfamily (Autotransporte_beta_dom_sf)
Type: Homologous_superfamily

Secretion of protein products occurs by a number of different pathways in bacteria. One of these pathways known as the type V pathway was first described for the IgA1 protease . The protein component that mediates secretion through the outer membrane is contained within the secreted protein itself, hence the proteins secreted in this way are called autotransporters . This superfamily corresponds to the presumed integral membrane β-barrel domain that transports the protein. This domain is found at the C terminus of the proteins it occurs in. The N terminus contains the variable passenger domain that is translocated across the membrane. Once the passenger domain is exported it is cleaved auto-catalytically in some proteins, in others a different protease is used and in some cases no cleavage occurs .
RNA polymerase Rpb5, N-terminal domain superfamily (RNA_pol_Rpb5_N_sf)
Type: Homologous_superfamily

Prokaryotes contain a single DNA-dependent RNA polymerase (RNAP;

) that is responsible for the transcription of all genes, while eukaryotes have three classes of RNAPs (I-III) that transcribe different sets of genes. Each class of RNA polymerase is an assemblage of ten to twelve different polypeptides. Certain subunits of RNAPs, including RPB5 (POLR2E in mammals), are common to all three eukaryotic polymerases. RPB5 plays a role in the transcription activation process. Eukaryotic RPB5 has a bipartite structure consisting of a unique N-terminal region, plus a C-terminal region that is structurally homologous to the prokaryotic RPB5 homologue, subunit H (gene rpoH) (

) .

This entry represents the N-terminal domain superfamily of eukaryotic RPB5, which has a core structure consisting of three layers (α/β/α) . The N-terminal domain is involved in DNA binding and is part of the jaw module in the RNA pol II structure . This module is important for positioning the downstream DNA.
VSV matrix superfamily (VSV_matrix_sf)
Type: Homologous_superfamily

This superfamily consists of several Vesiculovirus matrix proteins. The matrix (M) protein of vesicular stomatitis virus (VSV) expressed in the absence of other viral components causes many of the cytopathic effects of VSV, including an inhibition of host gene expression and the induction of cell rounding. It has been shown that M protein also induces apoptosis in the absence of other viral components. It is thought that the activation of apoptotic pathways causes the inhibition of host gene expression and cell rounding by M protein . Structurally, the M protein consists of a single globular domain .
Amb V Allergen superfamily (Amb_V_allergen_sf)
Type: Homologous_superfamily

Amb V is an Ambrosia sp (ragweed) pollen allergen. Amb t V has been shown to contain a C-terminal helix as the major T cell epitope. Free sulphydryl groups also play a major role in the T cell recognition of cross-reactivity T cell epitopes within these related allergens .

Structurally, Amb V has an α+β fold composed of three antiparallel strands followed by a short α helix.
TmoB-like superfamily (TmoB-like_sf)
Type: Homologous_superfamily

This superfamily consists of several Toluene-4-monooxygenase system protein B (TmoB) sequences. Pseudomonas mendocina KR1 metabolises toluene as a carbon source. The initial step of the pathway is hydroxylation of toluene to form p-cresol by a multicomponent toluene-4-monooxygenase (T4MO) system .
Flavinator of succinate dehydrogenase superfamily (SDH_sf)
Type: Homologous_superfamily

This superfamily includes the highly conserved mitochondrial and bacterial proteins Sdh5/SDHAF2/SdhE.

Both yeast and human Sdh5/SDHAF2, which are mitochondrial succinate dehydrogenase assembly factors, interact with the catalytic subunit of the succinate dehydrogenase (SDH) complex, a component of both the electron transport chain and the tricarboxylic acid cycle. Sdh5 is required for SDH-dependent respiration and for Sdh1 flavination (incorporation of the flavin adenine dinucleotide cofactor). Mutational inactivation of Sdh5 confers tumor susceptibility in humans .
Alpha-2,3-sialyltransferase superfamily (A-2_3-sialylTrfase_sf)
Type: Homologous_superfamily

This entry represents several alpha-2,3-sialyltransferase (

) proteins, most of which are found in the food-borne pathogen Campylobacter jejuni. Sialyltransferases transfer a sialic acid moiety from cytidine-5'-monophospho-N-acetyl-neuraminic acid (CMP-NeuAc) to terminal positions of various key glycoconjugates, which play critical roles in cell recognition and adherence . The structure of Cst-II alpha-2,3-sialyltransferase from C. jejuni consists of a 3-layer α/β/α topology. Cst-II catalytic mechanism involves an essential histidine (general base) and two tyrosine residues (coordination of the phosphate leaving group) to carry out substrate binding and glycosyl transfer.

This superfamily also includes 3-deoxy-D-manno-oct-2-ulosonate III transferase WaaZ (

), also known as Kdo-III transferase .
Pesticidal crystal protein, N-terminal domain superfamily (Pest_crys_N_sf)
Type: Homologous_superfamily

This entry represents the conserved N-terminal domain superfamily of the pesticidal crystal protein toxic core.

The crystal proteins of Bacillus thuringiensis have been extensively studied because of their pesticidal properties and their high natural levels of production . When an insect ingests these proteins, they are activated by proteolytic cleavage. The N terminus is cleaved in all of the proteins and a C-terminal extension is cleaved in some members. Once activated, the endotoxin binds to the gut epithelium and causes cell lysis by the formation of cation-selective channels, which leads to death. The activated region (toxic core) of the toxin is composed of three distinct structural domains: an N-terminal helical bundle domain (

) involved in membrane insertion and pore formation; a β-sheet central domain involved in receptor binding; and a C-terminal β-sandwich domain (

) that interacts with the N-terminal domain to form a channel .
GFRP superfamily (GFRP_sf)
Type: Homologous_superfamily

GTP cyclohydrolase I feedback regulatory protein (GFRP) in mammals helps regulate the biosynthesis of tetrahydrobiopterin through the feedback inhibition of the rate-limiting enzyme GTP cyclohydrolase I (GTPCHI). Tetrahydrobiopterin is the cofactor required for the hydroxylation of aromatic amino acids. The crystal structure of GFRP reveals that the protein forms a homopentamer . In the presence of phenylalanine, the stimulatory complex consists of a GTPCHI decamer sandwiched by two GFRP pentamers, which is thought to enhance GTPCHI activity by locking the enzyme in the active state . The structure of GFRP consists of two α/β layers arranged β(2)-α-β(2)-α-β(2), with antiparallel β-sheets in the order 342165.
Quinohemoprotein amine dehydrogenase alpha subunit, domain 2 superfamily (H-AmDH_asu_dom2_sf)
Type: Homologous_superfamily

Quinohemoprotein amine dehydrogenases (QHNDH)

) are enzymes produced in the periplasmic space of certain Gram-negative bacteria, such as Paracoccus denitrificans and Pseudomonas putida, in response to primary amines, including n-butylamine and benzylamine. QHNDH catalyses the oxidative deamination of a wide range of aliphatic and aromatic amines through formation of a Schiff-base intermediate involving one of the quinone O atoms . Catalysis requires the presence of a novel redox cofactor, cysteine tryptophylquinone (CTQ). CTQ is derived from the post-translational modification of specific residues, which involves the oxidation of the indole ring of a tryptophan residue to form tryptophylquinone, followed by covalent cross-linking with a cysteine residue . There is one CTQ per subunit in QHNDH. In addition to CTQ, two haem c cofactors are present in QHNDH that mediate the transfer of the substrate-derived electrons from CTQ to an external electron acceptor, cytochrome c-550 .

QHNDH is a heterotrimer of alpha, beta and gamma subunits. The alpha and beta subunits contain signal peptides necessary for the translocation of QHNDH to the periplasm. The alpha subunit is composed of four domains - domain 1 forming a dihaem cytochrome, and domains 2-4 forming antiparallel β-barrel structures; the beta subunit is a 7-bladed β-propeller that provides part of the active site; and the small, catalytic gamma subunit contains the novel cross-linked CTQ cofactor, in addition to additional thioester cross-links between Cys and Asp/Glu residues that encage CTQ. The gamma subunit assumes a globular secondary structure with two short α-helices having many turns and bends .

This entry represents the second domain found in the QHNDH alpha subunit.
Neurotransmitter-gated ion-channel transmembrane domain superfamily (Neuro-gated_channel_TM_sf)
Type: Homologous_superfamily

Neurotransmitter ligand-gated ion channels are transmembrane receptor-ion channel complexes that open transiently upon binding of specific ligands, allowing rapid transmission of signals at chemical synapses . Five of these ion channel receptor families have been shown to form a sequence-related superfamily:

Nicotinic acetylcholine receptor (AchR), an excitatory cation channel in vertebrates and invertebrates; in vertebrate motor endplates it is composed of alpha, beta, gamma and delta/epsilon subunits; in neurons it is composed of alpha and non-alpha (or beta) subunits .

Glycine receptor, an inhibitory chloride ion channel composed of alpha and beta subunits .

Gamma-aminobutyric acid (GABA) receptor, an inhibitory chloride ion channel; at least four types of subunits (alpha, beta, gamma and delta) are known .

Serotonin 5HT3 receptor, of which there are seven major types (5HT3-5HT7) .

Glutamate receptor, an excitatory cation channel of which at least three types have been described (kainate, N-methyl-D-aspartate (NMDA) and quisqualate) .

These receptors possess a pentameric structure (made up of varying subunits), surrounding a central pore. All known sequences of subunits from neurotransmitter-gated ion-channels are structurally related. They are composed of a large extracellular glycosylated N-terminal ligand-binding domain, followed by three hydrophobic transmembrane regions which form the ionic channel, followed by an intracellular region of variable length. A fourth hydrophobic region is found at the C-terminal of the sequence .

This domain represents four transmembrane helices of a variety of neurotransmitter-gated ion-channels.
Ran-GTPase activating protein 1, C-terminal domain superfamily (RanGAP1_C_sf)
Type: Homologous_superfamily

Ran GTPase is a ubiquitous protein required for nuclear transport, spindle assembly, nuclear assembly and mitotic cell cycle regulation. RanGTPase activating protein 1 (RanGAP1) is one of several RanGTPase accessory proteins. During interphase, RanGAP1 is located in the cytoplasm, while during mitosis it becomes associated with the kinetochores . Cytoplasmic RanGAP1 is required for RanGTPase-directed nuclear transport. The activity of RanGAP1 requires the accessory protein RanBP1. RanBP1 facilitates RanGAP1 hydrolysis of Ran-GTP, both directly and by promoting the dissociation of Ran-GTP from transport receptors, which would otherwise block RanGAP1-mediated hydrolysis. RanGAP1 is thought to bind to the Switch 1 and Switch 2 regions of RanGTPase. The Switch 2 region can be buried in complexes with karyopherin-beta2, and requires the interaction with RanBP1 to permit RanGAP1 function. RanGAP1 can undergo SUMO (small ubiquitin-like modifier) modification, which targets RanGAP1 to RanBP2/Nup358 in the nuclear pore complex, and is required for association with the nuclear pore complex and for nuclear transport . The enzymes involved in SUMO modification are located on the filaments of the nuclear pore complex.

The RanGAP1 N-terminal domain is fairly well conserved between vertebrate and fungal proteins, but yeast does not contain the C-terminal domain. The C-terminal domain is SUMO-modified and required for the localisation of RanGAP1 at the nuclear pore complex. The structure of the C-terminal domain is multihelical, consisting of two curved α/α layers in a right-handed superhelix.