SII-SWORD/CoKE huggingface dataset:
tRNA intron endonuclease, N-terminal domain superfamily (tRNA_intron_Endonuc_N_sf)
Type: Homologous_superfamily

This entry represents a 2-layer α/β domain superfamily found at the N terminus of the homotetrameric tRNA-intron endonucleases , and as domains 1 (N-terminal) and 3 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 2 bulged loops of 3 bases are separated by a stem of 4 bp . Although homotetrameric enzymes contain four active sites, only two participate in the cleavage, and should therefore, be considered as a dimer of dimers.
TAFII-230 TBP-binding domain superfamily (TAFII-230_TBP-bd_sf)
Type: Homologous_superfamily

In eukaryotes, the general transcription factor TFIID helps to regulate transcription by RNA polymerase II from class II promoters. TFIID consists of TATA-box-binding proteins (TBP) and TBP-associated factors (TAFIIs), which together mediate both activation and inhibition of transcription. In Drosophila, the N-terminal region of TAFII-230 (the TFIID 230kDa subunit) binds directly to TBP, thereby inhibiting the binding of TBP to the TATA box. The N-terminal domain is comprised of three α helices and a β hairpin, which forms the core that occupies the DNA-binding surface of TBP .
ATP synthase, F1 complex, epsilon subunit superfamily, mitochondrial (ATP_synth_F1_esu_sf_mt)
Type: Homologous_superfamily

This superfamily constitutes the mitochondrial ATP synthase epsilon subunit, which is distinct from the bacterial epsilon subunit (the latter being homologous to the mitochondrial delta subunit,

). The mitochondrial epsilon subunit is located in the stalk region of the F1 complex, and acts as an inhibitor of the ATPase catalytic core. The epsilon subunit can assume two conformations, contracted and extended, where the latter inhibits ATP hydrolysis. The conformation of the epsilon subunit is determined by the direction of rotation of the gamma subunit, and possibly by the presence of ADP. The extended epsilon subunit is thought to become extended in the presence of ADP, thereby acting as a safety lock to prevent wasteful ATP hydrolysis .

In Drosophila, the protein Stunted which activates the G-protein coupled receptor Methuselah in vitro, leading to increased intracellular calcium ion levels, is embryonically lethal .

F-ATPases (also known as ATP synthases, F1F0-ATPase, or H(+)-transporting two-sector ATPase) (

) are composed of two linked complexes: the F1 ATPase complex is the catalytic core and is composed of 5 subunits (alpha, beta, gamma, delta, epsilon), while the F0 ATPase complex is the membrane-embedded proton channel that is composed of at least 3 subunits (A-C), with additional subunits in mitochondria. Both the F1 and F0 complexes are rotary motors that are coupled back-to-back. In the F1 complex, the central gamma subunit forms the rotor inside the cylinder made of the α(3)β(3) subunits, while in the F0 complex, the ring-shaped C subunits forms the rotor. The two rotors rotate in opposite directions, but the F0 rotor is usually stronger, using the force from the proton gradient to push the F1 rotor in reverse in order to drive ATP synthesis . These ATPases can also work in reverse in bacteria, hydrolysing ATP to create a proton gradient.

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.
Actin-related protein 2/3 complex subunit 5 superfamily (ARPC5_sf)
Type: Homologous_superfamily

Arp2/3 binds to pre-existing actin filaments and nucleates new daughter filaments, and thus becomes incorporated into the dynamic actin network at the leading edge of motile cells and other actin-based protrusive structures . In order to nucleate filaments, Arp2/3 must bind to a member of the N-WASp/SCAR family protein . Arp2 and Arp3 are thought to be brought together after activation, forming an actin-like nucleus for actin monomers to bind and create a new actin filament. In the absence of an activating protein, Arp2/3 shows very little nucleation activity. Recent research has focused on the binding and hydrolysis of ATP by Arp2 and Arp3 , and crystal structures of the Arp2/3 complex have been solved .

The human Arp2/3 complex consists of ARP2, ARP3, ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC and ARPC5/p16-ARC. This superfamily represents the ARPC5/p16-ARC subunit. This subunit has a multihelical structure composed of two (curved) layers: α/α and a right-handed superhelix.
RAP domain superfamily (RAP_sf)
Type: Homologous_superfamily

The alpha-2-macroglobulin receptor-associated protein (RAP) is a glycoprotein that binds to the alpha-2-macroglobulin receptor, as well as to other members of the low density lipoprotein receptor family (

). RAP acts to inhibit the binding of all know ligands for these receptors, and may prevent receptor aggregation and degradation in the endoplasmic reticulum, thereby acting as a molecular chaperone . RAP may be under the regulatory control of calmodulin, since it is able to bind calmodulin and be phosphorylated by calmodulin-dependent kinase II (

).

RAP is comprised of three domains, each representing about one-third of the protein, which originated from an apparent triplication of an approximately 100 residue sequence. The second and third domains interact weakly with one another, whereas the first domain is entirely independent . Structural studies have revealed the first RAP domain to comprise of a partly opened bundle of three helices, the first one being shorter than the other two.
DNA polymerase III-theta superfamily (PolIII_theta_sf)
Type: Homologous_superfamily

This entry represents the theta subunit of DNA polymerase III from bacteria, whose core structure consists of an irregular array of three helices .

DNA polymerase III (Pol III) is the primary enzyme responsible for replication of Escherichia coli chromosomal DNA. The holoenzyme consists of 17 proteins and contains two core polymerases. The Pol III catalytic core has three tightly associated subunits: alpha, epsilon and theta. The alpha subunit is responsible for the DNA polymerase activity, while the epsilon subunit is the 3'-5' proofreading exonuclease. The epsilon subunit binds to both the alpha and theta subunits in the linear order α-ε-theta. The theta subunit is the smallest, and may act to enhance the proofreading activity of epsilon, especially under extreme conditions .

This superfamily also includes the uncharacterised protein YibT from Salmonella sp.
TT1725-like superfamily (TT1725-like_sf)
Type: Homologous_superfamily

This is a superfamily of conserved hypothetical bacterial proteins, including TT1725 from Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579), which has a ferredoxin-like α+β-sandwich fold .
Histone chaperone ASF1-like superfamily (ASF1-like_sf)
Type: Homologous_superfamily

This family includes the yeast and human ASF1 protein. These proteins have histone chaperone activity . ASF1 participates in both the replication-dependent and replication-independent pathways. The structure three-dimensional has been determined as a compact immunoglobulin-like β-sandwich fold topped by three helical linkers .
MTH938-like superfamily (MTH938-like_sf)
Type: Homologous_superfamily

MTH938 is a hypothetical protein encoded by Methanobacterium thermoautotrophicum. The crystal structure of MTH938 consists of three β-sheets and three α-helices .

This superfamily also includes NDUFAF3, an essential factor for the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I) , and Mth938 domain-containing protein .
Expansin, cellulose-binding-like domain superfamily (Expansin_CBD_sf)
Type: Homologous_superfamily

Expansins are secreted proteins of 25 to 27 Kd that were isolated first from young cucumber seedling and subsequently from other plant tissues. Expression of expansin genes correlates with growth of cells. Increase in expansin content also occurs during fruit ripening. Expansins act on the cell wall to promote its extensibility. The model for its mechanism of action postulates that expansins break non-covalent bonds between cell-wall polysaccharides, thereby permitting pressure dependent expansion of the cell .

Group-I pollen allergens of grasses have limited but significant sequence homology to expansin. These proteins are the main causative agent of hay fever and seasonal asthma induced by grass pollen. Extracts containing group-I allergens are also active in loosening cell-walls. Group-I pollen allergens and related proteins in vegetative tissues have been classified as beta-expansins, whereas the earlier discovered expansins are now referred as α-expansins .

Expansins consist of two domains closely packed and aligned so as to form a long, shallow groove with potential to bind a glycan backbone of ~10 sugar residues. The N-terminal cysteine-rich domain has distant sequence similarity to family-45 endoglucanases (EG45-like domain). The ~90-residue C-terminal domain may function as a cellulose-binding domain (CBD). It is composed of eight β-strands assembled into two antiparallel β-sheets. The two β-sheets are at slight angles to each other and form a β-sandwich similar to the Ig fold .

This entry represents the expansin CBD-like domain superfamily.
Stage V sporulation protein G superfamily (SpoVG_sf)
Type: Homologous_superfamily

This entry represents the stage V sporulation protein G (SpoVG) superfamily. It is essential for sporulation and specific to stage V sporulation in Bacillus megaterium and Bacillus subtilis . In B. subtilis, expression decreases after 30-60 minutes of cold shock .

Structurally, SpoVG comprises a coiled antiparallel β-sheet packed against the C-terminal helix. In addition, the extensions of strands 4 and 5 form an isolated β-hairpin.
Actin-related protein 2/3 complex subunit 3 superfamily (ARPC3_sf)
Type: Homologous_superfamily

Arp2/3 binds to pre-existing actin filaments and nucleates new daughter filaments, and thus becomes incorporated into the dynamic actin network at the leading edge of motile cells and other actin-based protrusive structures . In order to nucleate filaments, Arp2/3 must bind to a member of the N-WASp/SCAR family protein . Arp2 and Arp3 are thought to be brought together after activation, forming an actin-like nucleus for actin monomers to bind and create a new actin filament. In the absence of an activating protein, Arp2/3 shows very little nucleation activity. Recent research has focused on the binding and hydrolysis of ATP by Arp2 and Arp3 , and crystal structures of the Arp2/3 complex have been solved .

The human complex consists of Arp2/3 complex composed of ARP2, ARP3, ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC and ARPC5/p16-ARC. This superfamily represents the ARPC3/p21-ARC subunit. This subunit is composed of five helices, where one helix is surrounded by the others.
YbaK/aminoacyl-tRNA synthetase-associated domain superfamily (YbaK/aa-tRNA-synt-asso_dom_sf)
Type: Homologous_superfamily

Bacterial prolyl-tRNA synthetases and some smaller paralogues, YbaK and ProX, can hydrolyse misacylated Cys-tRNA(Pro) or Ala-tRNA(Pro) . The small bacterial protein Ybak preferentially hydrolyses Cys-tRNA(Pro) and Cys-tRNA(Cys) . ProX functions in trans to edit the amino acid moiety from incorrectly charged Ala-tRNA(Pro) . Prolyl-tRNA synthetases main function is to catalyse the attachment of proline to tRNA(Pro) in a two-step reaction: proline is first activated by ATP to form Pro-AMP and then transferred to the acceptor end of tRNA(Pro) .

This entry represents a domain superfamily characteristic of Ybak and ProX, that can also be found with other domains in prolyl-tRNA synthetases. The core structure of this domain has an α-β-α-β(2)-(α-β)2-α-β(2)-α-β fold arranged into three layers with bifurcated mixed sheet.
SRS domain superfamily (SRS_dom_sf)
Type: Homologous_superfamily

Toxoplasma gondii is a persistent protozoan parasite capable of infecting almost any warm-blooded vertebrate. The surface of Toxoplasma is coated with a family of developmentally regulated glycosylphosphatidylinositol (GPI)-linked proteins (SRSs), of which SAG1 is the prototypic member. SRS proteins mediate attachment to host cells and interface with the host immune response to regulate the virulence of the parasite. SAG1 is composed of two disulphide linked SRS domains. These have 6 cysteines that form 1-6,2-5 and 3-4 pairings. The structure of the immunodominant SAG1 antigen reveals a homodimeric configuration with SS-crosslinked β-sandwich of distinct geometry but topologically similar to cupredoxins. The SRS domain superfamily is found in a single copy in the SAG2 proteins. This family of surface antigens are found in other apicomplexans.
H/ACA ribonucleoprotein complex, subunit Nop10 superfamily (H/ACA_rnp_Nop10_sf)
Type: Homologous_superfamily

H/ACA ribonucleoprotein particles (RNPs) are a family of RNA pseudouridine synthases that specify modification sites through guide RNAs. The function of these H/ACA RNPs is essential for biogenesis of the ribosome, splicing of precursor mRNAs (pre-mRNAs), maintenance of telomeres and probably for additional cellular processes . All H/ACA RNPs contain a specific RNA component (snoRNA or scaRNA) and at least four proteins common to all such particles: Cbf5, Gar1, Nhp2 and Nop10. These proteins are highly conserved from yeast to mammals and homologues are also present in archaea . The H/ACA protein complex contains a stable core composed of Cbf5 and Nop10, to which Gar1 and Nhp2 subsequently bind .

In eukaryotes Nop10 is a nucleolar protein that is specifically associated with H/ACA snoRNAs. It is essential for normal 18S rRNA production and rRNA pseudouridylation by the ribonucleoprotein particles containing H/ACA snoRNAs (H/ACA snoRNPs). Nop10 is probably necessary for the stability of these RNPs . The Nop10 domain structure has a rubredoxin-like fold.
Transferrin receptor-like, dimerisation domain superfamily (TFR-like_dimer_dom_sf)
Type: Homologous_superfamily

This dimerisation domain can be found in the transferrin receptor, as well as in a number of other proteins including glutamate carboxypeptidase II and N-acetylated-alpha-linked acidic dipeptidase like protein.

The transferrin receptor (TfR) assists iron uptake into vertebrate cells through a cycle of endo- and exocytosis of the iron transport protein transferrin (Tf). TfR binds iron-loaded (diferric) Tf at the cell surface and carries it to the endosome, where the iron dissociates from Tf. The apo-Tf remains bound to TfR until it reaches the cell surface, where apo-Tf is replaced by diferric Tf from the serum to begin the cycle again. Human TfR is a homodimeric type II transmembrane protein. The crystal structure of a TfR monomer reveals a 3-domain structure: a protease-like domain that closely resembles carboxy- and amino-peptidases; an apical domain consisting of a β-sandwich; and a helical dimerisation domain. The dimerisation domain consists of a 4-helical bundle that makes contact with each of the three domains in the dimer partner .
At5g01610-like superfamily (At5g01610-like)
Type: Homologous_superfamily

This superfamily consists of several plant proteins of unknown function.
Thiamin pyrophosphokinase, catalytic domain superfamily (TPK_catalytic_sf)
Type: Homologous_superfamily

Thiamin pyrophosphokinase (TPK,

) catalyzes the transfer of a pyrophosphate group from ATP to vitamin B1 (thiamin) to form the coenzyme thiamin pyrophosphate (TPP). Thus, TPK is important for the formation of a coenzyme required for central metabolic functions. The structure of the thiamin pyrophosphokinase catalytic domain is composed of three layers (α/β/α) with parallel β-sheet of six strands. This structure suggests that the enzyme may operate by a mechanism of pyrophosphoryl transfer similar to those described for pyrophosphokinases functioning in nucleotide biosynthesis .
SspB-like superfamily (SspB-like_sf)
Type: Homologous_superfamily

Escherichia coli stringent starvation protein B (SspB), is thought to enhance the specificity of degradation of tmRNA-tagged proteins by the ClpXP protease. The tmRNA tag, also known as ssrA, is an 11-aa peptide added to the C terminus of proteins stalled during translation, targets proteins for degradation by ClpXP and ClpAP. SspB is a cytoplasmic protein that specifically binds to residues 1-4 and 7 of the tag. Binding of SspB enhances degradation of tagged proteins by ClpX, and masks sequence elements important for ClpA interactions, inhibiting degradation by ClpA . However, more recent work has cast doubt on the importance of SspB in wild-type cells . SspB is encoded in an operon whose synthesis is stimulated by carbon, amino acid, and phosphate starvation. SspB may play a special role during nutrient stress, for example by ensuring rapid degradation of the products of stalled translation, without causing a global increase in degradation of all ClpXP substrates .

The structure of SspB revealed an SH3-like topology, sharing some similarity with the Sm-like fold .
Lipid/polyisoprenoid-binding, YceI-like superfamily (TTHA0802/YceI-like_sf)
Type: Homologous_superfamily

This entry represents the lipid-binding protein YceI from Escherichia coli and the polyisoprenoid-binding protein TTHA0802 from Thermus thermophilus . Both these proteins share a common domain with an 8-stranded β-barrel fold, which resembles the lipocalin fold, although no sequence homology exists with lipocalins. In TTHA0802, the protein binds the polyisoprenoid chain within the pore of the barrel via hydrophobic interactions . Sequence homologues of this core structure are present in a wide range of bacteria and archaea. The crystal structures of Yce1 and TTHA0802 suggest that this family of proteins plays an important role in isoprenoid quinone metabolism and/or transport and/or storage .
IscX-like superfamily (IscX-like_sf)
Type: Homologous_superfamily

The ISC system is conserved in eubacteria and eukaryotes (mitochondria), and has broad specificity, targeting general FeS proteins . It is encoded by the isc operon (iscRSUA-hscBA-fdx-iscX). IscS is a cysteine desulphurase, which obtains S from cysteine (converting it to alanine) and serves as a S donor for FeS cluster assembly. IscU and IscA act as scaffolds to accept S and Fe atoms, assembling clusters and transfering them to recipient apoproteins. HscA is a molecular chaperone and HscB is a co-chaperone. Fdx is a [2Fe-2S]-type ferredoxin. IscR is a transcription factor that regulates expression of the isc operon. IscX (also known as YfhJ) appears to interact with IscS and may function as an Fe donor during cluster assembly .

This entry represents IscX proteins (also known as hypothetical protein YfhJ) that are part of the ISC system. IscX is active as a monomer. The structure of YfhJ is an orthogonal α-bundle . YfhJ is a small acidic protein that binds IscS, and contains a modified winged helix motif that is usually found in DNA-binding proteins . YfhJ/IscX can bind Fe, and may function as an Fe donor in the assembly of FeS clusters
Putative dsDNA mimic superfamily (Put_dsDNA_mimic_sf)
Type: Homologous_superfamily

This entry represents hypothetical proteins such as HI1450, which is believed to act as a putative dsDNA mimic. HI1450 is an acidic protein with a core structure consisting of α(2)-β(4), where the α-helices are packed against the side of an anti-parallel 4-stranded β meander. As such, it has some similarity to the dsDNA mimics uracil-DNA glycosylase inhibitor and nuclease A inhibitor (NuiA), including the distribution of surface charges and the position of the hydrophobic cavity . DNA mimics act to inhibit or regulate dsDNA-binding proteins.
Cysteine protease Prp superfamily (Peptidase_Prp_sf)
Type: Homologous_superfamily

This is a superfamily of cysteine protease that are found to cleave the N terminus extension of ribosomal subunit L27 in eubacteria. Proteins in this superfamily are distinguished by a pair of invariant histidine and cysteine residues with conserved spacing that form the classic catalytic dyad of a cysteine protease .
ZipA, C-terminal FtsZ-binding domain superfamily (ZipA_FtsZ-bd_C_sf)
Type: Homologous_superfamily

This entry represents the ZipA C-terminal domain superfamily. ZipA, a membrane-anchored protein, is an essential cell division protein involved in septum formation . FtsA and the C-terminal domain of ZipA bind FtsZ, a homologue of eukaryotic tubulins and a major component of the bacterial septal ring , at the prospective division site. This is followed by the sequential addition of FtsK, FtsQ, FtsL, FtsW, FtsI, and FtsN . ZipA contains three domains: a short N-terminal membrane-anchored domain, a central P/Q domain that is rich in proline and glutamine and a C-terminal domain, which comprises almost half the protein. The structure of the C-terminal domain is an α-β fold with three α helices and a β sheet of six antiparallel β strands. The major loops protruding from the β sheet surface are thought to form a binding site for FtsZ .
Fe(II) trafficking protein YggX superfamily (Fe_traffick_prot_YggX_sf)
Type: Homologous_superfamily

The protein superfamily represented by this entry, YggX, serves to protect Fe-S clusters from oxidative damage . The effect is two-fold: proteins that rely on Fe-S clusters do not become inactivated, and the release of free iron and hydrogen peroxide--a DNA damaging agent--is prevented. These observations are consistent with the hypothesis that YggX chelates free iron, and recent experiments show that YggX can indeed bind Fe(II) in vitro and in vivo . Furthermore, YggX has a positive effect on the action of at least one Fe(II)-responsive protein. The combined actions of YggX is reminiscent of iron trafficking proteins , and YggX is therefore proposed to play a role in Fe(II) trafficking . In Escherichia coli, YggX was shown to be under the transcriptional control of the redox-sensing SoxRS system .

Structurally, YggX has a β(2)-α(3) fold and contains a zinc-less 'zinc finger'-like fold.
ApaG domain superfamily (ApaG_sf)
Type: Homologous_superfamily

The apaG domain is a ~125 amino acids domain present in bacterial apaG proteins and in eukaryotic F-box proteins. The domain is named after the bacterial apaG protein, of which it forms the core. The domain also occurs in the C-terminal part of eukaryotic proteins with an N-terminal F-box domain. The Salmonella typhimurium apaG domain protein corD is involved in Co(2+) resistance and Mg(2+) efflux. Tertiary structures from different apaG proteins show a fold of several β-sheets. The apaG domain may be involved in protein-protein interactions which could be implicated in substrate-specificity .
DNA polymerase III subunit chi superfamily (PolIII_chi_sf)
Type: Homologous_superfamily

The DNA polymerase III holoenzyme (

) is the polymerase responsible for the replication of the Escherichia coli chromosome. The holoenzyme is composed of the DNA polymerase III core, the sliding clamp, and the DnaX clamp loading complex. The DnaX complex contains either the tau or gamma product of gene dnax, complexed to delta.delta and to chi psi. Chi forms a 1:1 heterodimer with psi. The chi psi complex functions by increasing the affinity of tau and gamma for delta.delta allowing a functional clamp-loading complex to form at physiological subunit concentrations. Psi is responsible for the interaction with DnaX (gamma/tau), but psi is insoluble unless it is in a complex with chi . Members of this protein family are mainly found in proteobacteria.