SII-SWORD/CoKE huggingface dataset:
RPB6/omega subunit-like superfamily (RPB6/omega-like_sf)
Type: Homologous_superfamily

In eukaryotes, there are three different forms of DNA-dependent RNA polymerases (

) transcribing different sets of genes. Each class of RNA polymerase is an assemblage of ten to twelve different polypeptides. In archaebacteria, there is generally a single form of RNA polymerase which also consists of an oligomeric assemblage of 10 to 13 polypeptides. A component of 14 to 18kDa shared by all three forms of eukaryotic RNA polymerases and which has been sequenced in budding yeast (gene RPB6 or RPO26), in Schizosaccharomyces pombe (Fission yeast) (gene rpb6 or rpo15), in human and in African swine fever virus (ASFV) is evolutionary related to the archaebacterial subunit Rpo6 (also known as subunit K). The archaebacterial protein is colinear with the C-terminal part of the eukaryotic subunit.

The structures of the omega subunit and RBP6, and the structures of the omega/beta' and RPB6/RPB1 interfaces, suggest a molecular mechanism for the function of omega and RPB6 in promoting RNAP assembly and/or stability. The conserved regions of omega and RPB6 form a compact structural domain that interacts simultaneously with conserved regions of the largest RNAP subunit and with the C-terminal tail following a conserved region of the largest RNAP subunit. The second half of the conserved region of omega and RPB6 forms an arc that projects away from the remainder of the structural domain and wraps over and around the C-terminal tail of the largest RNAP subunit, clamping it in a crevice, and threading the C-terminal tail of the largest RNAP subunit through the narrow gap between omega and RPB6 .
Resolvase-like, N-terminal catalytic domain superfamily (Resolvase-like_N_sf)
Type: Homologous_superfamily

Site-specific recombination plays an important role in DNA rearrangement in prokaryotic organisms. Two types of site-specific recombination are known to occur:

Recombination between inverted repeats resulting in the reversal of a DNA segment.

Recombination between repeat sequences on two DNA molecules resulting in their cointegration, or between repeats on one DNA molecule resulting in the excision of a DNA fragment.

Site-specific recombination is characterised by a strand exchange mechanism that requires no DNA synthesis or high energy cofactor; the phosphodiester bond energy is conserved in a phospho-protein linkage during strand cleavage and re-ligation.

Two unrelated families of recombinases are currently known . The first, called the 'phage integrase' family, groups a number of bacterial phage and yeast plasmid enzymes. The second , called the 'resolvase' family, groups enzymes which share the following structural characteristics: an N-terminal catalytic and dimerization domain that contains a conserved serine residue involved in the transient covalent attachment to DNA, and a C-terminal helix-turn-helix DNA-binding domain (

).
Heavy metal-associated domain superfamily (HMA_dom_sf)
Type: Homologous_superfamily

Proteins that transport heavy metals in micro-organisms and mammals share similarities in their sequences and structures.

These proteins provide an important focus for research, some being involved in bacterial resistance to toxic metals, such as lead and cadmium, while others are involved in inherited human syndromes, such as Wilson's and Menke's diseases .

A conserved domain has been found in a number of these heavy metal transport or detoxification proteins . The domain, which has been termed Heavy-Metal-Associated (HMA), contains two conserved cysteines that are probably involved in metal binding.

Structure solution of the fourth HMA domain of the Menke's copper transporting ATPase shows a well-defined structure comprising a four-stranded antiparallel β-sheet and two α-helices packed in an α-β sandwich fold . This fold is common to other domains and is classified as "ferredoxin-like".
Large ribosomal subunit protein bL21-like superfamily (bL21-like_sf)
Type: Homologous_superfamily

This superfamily includes the large ribosomal subunit protein bL21 (previously known as L21) that is found in bacteria and eukaryotic organelles such as chloroplast and mitochondria. This entry also includes the S. pombe Aco2 protein, a fusion of mitochondrial ribosomal protein bL21m (Mrpl49) and aconitase that has essential function in mitochondrial translation in fission yeast. bL21 consists of a small β-barrel-like domain that is connected to an extended loop .

In Escherichia coli, bL21 is known to bind to the 23S rRNA in the presence of bL20. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities, groups:

Bacterial bL21 (old name L21).

Marchantia polymorpha chloroplast bL21 (old name L21).

Plant chloroplast bL21 (old name L21, nuclear-encoded).

Bacterial bL21 is a protein of about 100 amino-acid residues, the mature form of the spinach chloroplast L21 has 200 residues.
YefM-like superfamily (YefM-like_sf)
Type: Homologous_superfamily

Members of this superfamily act as antitoxins in type II toxin-antitoxin systems . When bound to their toxin partners, they can bind DNA via the N terminus and repress the expression of operons containing genes encoding the toxin and the antitoxin .

The structure of YefM has a β-α(2)-β(2)-α fold with mixed β-sheet where strands 1 and 2 are parallel. It forms a compact dimer with a single β-sheet topology.
YxeA-like superfamily (YxeA-like_sf)
Type: Homologous_superfamily

This entry represents a superfamily of small (about 115 amino acids) uncharacterised proteins with N-terminal signal sequences, found predominantly in Gram-positive organisms. Most genomes that have any members of this family have at least two members. This entry includes YxeA from Bacillus subtilis, which is transcriptionally regulated by YxdJ .
tRNA intron endonuclease, catalytic domain-like superfamily (tRNA_intron_Endo_cat-like_sf)
Type: Homologous_superfamily

This entry represents a three-layer α/β/α domain found as the catalytic domain at the C-terminal in homotetrameric tRNA-intron endonucleases , and as domains 2 and 4 (C-terminal) in the homodimeric enzymes . tRNA-intron endonucleases (

) remove tRNA introns by cleaving pre-tRNA at the 5'- and 3'-splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3' cyclic phosphate and 5'-hydroxyl termini . These enzymes recognise a pseudosymmetric substrate in which two bulged loops of three bases are separated by a stem of four bp . Although homotetrameric enzymes contain four active sites, only two participate in the cleavage, and should therefore, be considered as a dimer of dimers.
AP-2 complex subunit mu, C-terminal superfamily (AP2_Mu_C_sf)
Type: Homologous_superfamily

This superfamily describes the C-terminal domain of the Mu subunit (Mu2-adaptin, AP50) of adaptor protein (AP) complexes AP-1, AP-2, AP-3, and AP-4. It has an elongated, banana-shaped, all β-sheet structure. It can be considered as two β-sandwich subdomains (A and B), with subdomain B inserted between strands 6 and 15 of subdomain A, and joined edge to edge such that the convex surface is a continuous nine-stranded mixed β-sheet that runs the whole length of the molecule. The tyrosine based signal binds to a site on the surface of two parallel β-sheet strands (β1 and β16) in subdomain A .
DXP reductoisomerase, C-terminal domain superfamily (DXPR_C_sf)
Type: Homologous_superfamily

This entry represents the C-terminal domain of the 1-deoxy-D-xylulose-5-phosphate reductoisomerase enzymes. This domain forms a left handed super-helix. DXP reductoisomerase catalyses the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP) .
Immunity protein YezG-like superfamily (YezG-like_sf)
Type: Homologous_superfamily

Proteins in this entry include the Immunity protein YezG from Bacillus subtilis and Type VII secretion system protein EsaG from Staphylococcus aureus. YezG is the antitoxin component of a LXG toxin-antitoxin (TA) module that promote kin selection, mediate competition in biofilms, and drive spatial segregation of different strains, probably helping to avoid warfare between strains in biofilms . EsaG is part of toxin-antitoxin system that counteracts the toxic effect of EssD via direct interaction .

YezG has an α/β structure with an antiparallel β-sheet.
Ta0354, soluble domain superfamily (Ta0354_soluble_sf)
Type: Homologous_superfamily

This superfamily describes a domain found at the C terminus of a family of archaeal putative membrane proteins. It consists of a 3 helix bundle fold.
Apolipoprotein A-II (ApoA-II) superfamily (ApoA-II_sf)
Type: Homologous_superfamily

Apolipoprotein A-II (ApoA-II) is the second major apolipoprotein of high density lipoprotein in human plasma. Mature ApoA-II is present as a dimer of two 77-amino acid chains joined by a disulphide bridge . ApoA-II regulates many steps in HDL metabolism, and its role in coronary heart disease is unclear . In bovine serum, the ApoA-II homologue is present in almost free form. Bovine ApoA-II shows antimicrobial activity against Escherichia coli and yeasts in phosphate buffered saline (PBS) .

ApoA-II structure presents a segmented tetrameric parallel coiled coil fold.
G39, N-terminal domain superfamily (G39-like_N_sf)
Type: Homologous_superfamily

This superfamily is represented by the N-terminal domain of Bacillus subtilis G39, composed of four helices.

G39P inhibits the initiation of DNA replication by blocking G40P replicative helicase. G39P has a bipartite structure consisting of a folded N-terminal domain and an unfolded C-terminal domain. The C-terminal domain is essential for helicase interaction .
Zinc finger, Sec23/Sec24-type superfamily (Znf_Sec23_Sec24_sf)
Type: Homologous_superfamily

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

COPII (coat protein complex II)-coated vesicles carry proteins from the endoplasmic reticulum (ER) to the Golgi complex . COPII-coated vesicles form on the ER by the stepwise recruitment of three cytosolic components: Sar1-GTP to initiate coat formation, Sec23/24 heterodimer to select SNARE and cargo molecules, and Sec13/31 to induce coat polymerisation and membrane deformation .

Sec23 p and Sec24p are structurally related, folding into five distinct domains: a β-barrel, a zinc-finger, an α/β trunk domain (

), an all-helical region (

), and a C-terminal gelsolin-like domain (

). This entry describes an approximately 55-residue Sec23/24 zinc-binding domain, which lies against the β-barrel at the periphery of the complex.
Sec23/Sec24 helical domain superfamily (Sec23/24_helical_dom_sf)
Type: Homologous_superfamily

COPII (coat protein complex II)-coated vesicles carry proteins from the endoplasmic reticulum (ER) to the Golgi complex . COPII-coated vesicles form on the ER by the stepwise recruitment of three cytosolic components: Sar1-GTP to initiate coat formation, Sec23/24 heterodimer to select SNARE and cargo molecules, and Sec13/31 to induce coat polymerisation and membrane deformation .

Sec23 p and Sec24p are structurally related, folding into five distinct domains: a β-barrel, a zinc-finger (

), an α/β trunk domain (

), an all-helical region, and a C-terminal gelsolin-like domain (

). This entry describes the all-helical domain, which forms an approximately 105-residue segment with the C-terminal 30 residues. The linker between alpha-M and alpha-N contacts Sar1.
E2 domain superfamily (E2_sf)
Type: Homologous_superfamily

The E2 domain is the largest of the conserved domains in the amyloidogenic glycoproteins. The structure of E2 consists of two coiled-coil sub-structures connected through a continuous helix, and bears an unexpected resemblance to the spectrin family of protein structures. E2 can reversibly dimerise in solution, and the dimerisation occurs along the longest dimension of the molecule in an antiparallel orientation, which enables the N-terminal substructure of one monomer to pack against the C-terminal substructure of a second monomer. The high degree of conservation of residues at the putative dimer interface suggests that the E2 dimer observed in the crystal could be physiologically relevant. Heparin sulphate proteoglycans, the putative ligands for the precursor present in extracellular matrix, bind to E2 at a conserved and positively charged site near the dimer interface . The E2 domain is also known as CAPPD (for central APP domain) .
Peptidase M55, D-aminopeptidase superfamily (Peptidase_M55_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 group of metallopeptidases belong to MEROPS peptidase family M55 (DppA aminopeptidase family, clan MN). The type example is Bacillus subtilis DppA, which is a binuclear zinc-dependent D-specific aminopeptidase. The structure reveals that DppA is an example of a self-compartmentalising protease, of which the proteasome is the most extensively studied. The DppA enzyme is composed of identical 30kDa subunits organised in a decamer with 52 point-group symmetry. A 20 A wide channel runs through the complex, giving access to a central chamber holding the active sites. DppA and its homologues are characterised by the presence of the SXDXEG motif . The only known substrates are D-Ala-D-Ala and D-Ala-Gly-Gly.

The DppA structure has a three-layer α/β/α fold with a parallel β-sheet of six strands, and a C-terminal α+β subdomain.
Formimidoyltransferase-cyclodeaminase-like superfamily (Formintransfe-cycloase-like_sf)
Type: Homologous_superfamily

Enzymes containing the cyclodeaminase domain function in channelling one-carbon units to the folate pool. In most cases, this domain catalyses the cyclisation of formimidoyltetrahydrofolate to methenyltetrahydrofolate as shown in reaction (1). In the methylotrophic bacterium Methylobacterium extorquens, however, it catalyses the interconversion of formyltetrahydrofolate and methylenetetrahydrofolate ,as shown in reaction (2)

(1) 5-formimidoyltetrahydrofolate = 5,10-methenyltetrahydrofolate + NH(3)

(2) 10- formyltetrahydrofolate = 5,10-methenyltetrahydrofolate + H(2)O

In prokaryotes, this domain mostly occurs on its own, while in eukaryotes it is fused to a glutamate formiminotransferase domain (which catalyses the previous step in the pathway) to form the bifunctional enzyme formiminotransferase-cyclodeaminase . The eukaryotic enzyme is a circular tetramer of homodimers , while the prokaryotic enzyme is a dimer .

The crystal structure of the cyclodeaminase enzyme (

) from Thermaotoga maritima has been studied . It is a homodimer, where each monomer is composed of six α helices arranged in an up and down helical bundle, forming a novel fold. The location of the active site is not known, but sequence alignments revealed two clusters of conserved residues located in a deep pocket within the dimmer interface. This pocket was large enough to accommodate the reaction product and it was postulated that this is the active site.
Immunoglobulin-like domain superfamily (Ig-like_dom_sf)
Type: Homologous_superfamily

The basic structure of immunoglobulin (Ig) molecules is a tetramer of two light chains and two heavy chains linked by disulphide bonds. There are two types of light chains: kappa and lambda, each composed of a constant domain (CL) and a variable domain (VL). There are five types of heavy chains: alpha, delta, epsilon, gamma and mu, all consisting of a variable domain (VH) and three (in alpha, delta and gamma) or four (in epsilon and mu) constant domains (CH1 to CH4). Ig molecules are highly modular proteins, in which the variable and constant domains have clear, conserved sequence patterns. The domains in Ig and Ig-like molecules are grouped into four types: V-set (variable;

), C1-set (constant-1;

), C2-set (constant-2;

) and I-set (intermediate;

) . Structural studies have shown that these domains share a common core Greek-key β-sandwich structure, with the types differing in the number of strands in the β-sheets as well as in their sequence patterns .

Immunoglobulin-like domains that are related in both sequence and structure can be found in several diverse protein families. Ig-like domains are involved in a variety of functions, including cell-cell recognition, cell-surface receptors, muscle structure and the immune system .
Gelsolin-like domain superfamily (Gelsolin-like_dom_sf)
Type: Homologous_superfamily

Gelsolin is a cytoplasmic, calcium-regulated, actin-modulating protein that binds to the barbed ends of actin filaments, preventing monomer exchange (end-blocking or capping) . It can promote nucleation (the assembly of monomers into filaments), as well as sever existing filaments. In addition, this protein binds with high affinity to fibronectin. Plasma gelsolin and cytoplasmic gelsolin are derived from a single gene by alternate initiation sites and differential splicing.

Sequence comparisons indicate an evolutionary relationship between gelsolin,
villin, fragmin and severin . Six large repeating segments occur in gelsolin and villin, and 3 similar segments in severin and fragmin. While the multiple repeats have yet to be related to any known function of the actin-severing proteins, the superfamily appears to have evolved from an ancestral sequence of 120 to 130 amino acid residues .

This gelsolin-like domain can also be found in the C-terminal of the members of Sec23/Sec24 family. They are components of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER).

The Gelsolin structure has a three layers (α/β/α) fold and a mixed β-sheet topology.
MIT domain superfamily (MIT_dom_sf)
Type: Homologous_superfamily

This entry represents the MIT domain superfamily.

The MIT domain forms an asymmetric three-helix bundle. It is found in vacuolar sorting proteins, spastin (probable ATPase involved in the assembly or function of nuclear protein complexes), and a sorting nexin, which may play a role in intracellular trafficking.

A 'variant' MIT domain has been described at the N-terminal region of a related AAA-ATPase, mammalian katanin p60 .

The MIT domain has a Spectrin repeat-like fold. This fold is composed of three helices in a close bundle topology. It has also a left-handed twist going up-and-down .
Copper chaperone PCuAC superfamily (PCuAC_sf)
Type: Homologous_superfamily

CuA is a dinuclear copper site within the soluble domain of subunit II (Cox2) of bacterial and eukaryotic cytochrome c oxidases (CcOs), whose function is to convey electrons from a soluble cytochrome c to the catalytic heme a3-CuB centre of CcO. The proper assembly of the CuA site is essential for the catalytic machinery of a functional oxidase. In prokaryotes two protein families have been proposed to be involved in CuA site formation, with a key role in the delivery of metal ions to the CuA site. The first includes proteins that are able to bind Cu(I) through methionine and histidine residues arranged in a highly conserved H(M)X(10)MX(21)HXM motif 5 (referred to as periplasmic CuA chaperone, PCu(A)C). The second consists of the Sco proteins, whose mechanism of action in CuA assembly as thioredoxins or metallochaperones is still debated. These proteins (PCuAC and Sco) are often found in the same bacterial operon, and most of the identified operons that encode Sco also contain a gene for Cox2 .

PCu(A)C is a periplasmic copper chaperone. It selectively inserts Cu(I) ions into subunit II of Thermus thermophilus ba3 oxidase to generate a native Cu(A) site. Its role may be to capture and transfer copper to two other copper chaperones, PrrC and Cox11, which in turn deliver Cu(I) to cytochrome c oxidase .
YajQ-like superfamily (YajQ-like_sf)
Type: Homologous_superfamily

This entry represents the UPF0234 family of uncharacterised proteins, which includes YajQ.

In Pseudomonas syringae, YajQ functions as a host protein involved in the temporal control of bacteriophage Phi6 gene transcription. It has been shown to bind to the phage's major structural core protein P1, most likely activating transcription by acting indirectly on the RNA polymerase. YajQ may remain bound to the phage particles throughout the infection period . Earlier, YajQ was characterised as a putative nucleic acid-binding protein based on the similarity of its (ferredoxin-like) three-dimensional topology with that of RNP-like RNA-binding domains .
IBP39, C-terminal domain superfamily (IBP39-like_C_sf)
Type: Homologous_superfamily

Initiator binding protein 39kDa (IBP39) recognises the initiator (Inr), which in Trichomonas vaginalis is solely responsible for transcription start site selection. IBP39 consists of an N-terminal Inr binding domain, a flexible linker, and a C-terminal domain. The C-terminal domain interacts with the RNAP II large subunit C-terminal domain. Binding of IBP39 to Inr recruits RNAP II and initiates transcription .
DNA helicase, DnaB-like, N-terminal domain superfamily (DNA_heli_DnaB-like_N_sf)
Type: Homologous_superfamily

The hexameric helicase DnaB unwinds the DNA duplex at the Escherichia coli chromosome replication fork. Although the mechanism by which DnaB both couples ATP hydrolysis to translocation along DNA and denatures the duplex is unknown, a change in the quaternary structure of the protein involving dimerization of the N-terminal domain has been observed and may occur during the enzymatic cycle. This N-terminal domain is required both for interaction with other proteins in the primosome and for DnaB helicase activity. This domain has a multi-helical structure that forms an orthogonal bundle .

It is also found in Replicative DNA helicase DnaC involved in the initiation and elongation during chromosome replication .