SII-SWORD/CoKE huggingface dataset:
YidC, periplasmic domain superfamily (YidC_periplasmic_sf)
Type: Homologous_superfamily

This is the periplasmic domain of YidC, a bacterial membrane protein which is required for the insertion and assembly of inner membrane proteins .
DHHA2 domain superfamily (DHHA2_dom_sf)
Type: Homologous_superfamily

This domain is called DHHA2 since it is often associated with the DHH domain and is diagnostic of DHH subfamily 2 members . The domain is about 120 residues long and contains a conserved DXK motif at its amino terminus. It is present in inorganic pyrophosphatases and in exopolyphosphatase of Saccharomyces cerevisiae.
DNA-mimic protein DMP12 superfamily (DMP12_sf)
Type: Homologous_superfamily

DMP12 is a DNA-mimic protein from Neisseria species. In its monomeric form DMP12 interacts with the Neisseria dimeric form of the bacterial histone-like protein HU. HU proteins promote the assembly of higher-order DNA-protein structures. The interaction between DMP12 and HU may be instrumental in controlling the stability of the nucleoid in Neisseria, as DMP12 prevents Neisseria HU protein from being digested by trypsin .
SATB, ULD domain superfamily (SATB_ULD_sf)
Type: Homologous_superfamily

This entry represents the N-terminal oligomerisation domain, also known as ULD domain, of the SATB (special AT-rich sequence-binding) protein. SATBs are global chromatin organisers and regulators of gene expression that are essential for T-cell development, breast cancer tumour growth and metastasis. SATBs assemble into a tetramer via the ULD (ubiquitin-like) domain, and the tetramerisation of SATBs is essential for recognising specific DNA sequences (such as multiple AT-rich DNA fragments). Thus, SATBs may regulate gene expression directly by binding to various promoters and upstream regions and thereby influencing promoter activity .
T6S-associated protein TagF superfamily (TagF_sf)
Type: Homologous_superfamily

This entry includes the T6S-associated protein, TagF, a post-translational repressor of the hemolysin co-regulated secretion island I (HSI-I)-encoded type VI secretion system (H1-T6SS), found in Pseudomonas aeruginosa. The type VI secretion system (T6SS) is found broadly among the Proteobacteria and is implicated in diverse processes including host-cell interactions, biofilm formation and gene regulation. Furthermore, studies indicate that the T6SS plays a critical role in interbacterial interactions. TagF has been shown to regulate the activity of the H1-T6SS in a manner that does not require phosphorylated-Fha1, PpkA, or other Tag proteins. TagF forms a homodimer with nearly identical monomers composed of alpha and beta elements assembled as a three-layer sandwich (α-β-α) .
LMG 18311 protein-like superfamily (LMG18311-like_sf)
Type: Homologous_superfamily

This superfamily includes a protein of unknown function from Streptococcus Thermophilus LMG 18311 whose structure has been determined (PDBe:2qzi) and related proteins.
PCGF Ub-like fold discriminator superfamily (PUFD_som_sf)
Type: Homologous_superfamily

The PUFD (PCGF Ub-like fold discriminator) domain is found at the C terminus of BCOR (BCL6 corepressor), and binds to the RAWUL (RING finger- and WD40-associated ubiquitin-like) domain of the polycomb-group protein PCGF1 . This domain is also found in BCORL1 (BCL6 corepressor-like), which also binds PCGF1 through its PUFD domain . Like BCOR, BCORL1 functions as a corepressor .
Syd superfamily (Syd_sf)
Type: Homologous_superfamily

This superfamily contains the Syd protein that has been implicated in the Sec-dependent transport of polypeptides across the inner membrane in bacteria. Syd has been shown to bind the SecY subunit of membrane-embedded SecYEG heterotrimer (also known as core translocon or SecY complex), which is a conserved protein-conducting channel essential for the biogenesis of most of the secretory and integral membrane proteins . The SecY-binding site of Syd is a conserved concave and electronegative groove that forms interactions with the electropositive loops of the SecY subunit . Syd is also known to verify the proper assembly of the SecY complex in the membrane by interfering with protein translocation only when the channel displays abnormal SecY-SecE associations .
Pathogenicity island component CagD superfamily (CagD_sf)
Type: Homologous_superfamily

CagD is a tightly conserved superfamily of proteins found in the pathogenic strains of Helicobacter species. It is one of some 30 proteins, produced from the genomic insert termed the pathogenicity island, required for the type IV secretion system - T4SS - that delivers CagA oncoprotein toxin into the host cell. CagD is a covalent dimer in which each monomer folds as a single domain composed of five β-strands and three α-helices. One of the β strands is responsible for dimerisation of CagD monomers, by interfacing with the equivalent strand on a separate CagD monomer. CagD partially associates with the inner membrane, where it may be exposed to the periplasmic space; this may indicate that CagD is released into the supernatant during host cell infection in order then to bind to the host cell surface, or to be incorporated into the pilus structure .
TBP-interacting protein, N-terminal superfamily (TIP_N_sf)
Type: Homologous_superfamily

This entry represents the N-terminal restriction endonuclease-like domain found in several archaeal TATA-binding protein (TBP)-interacting proteins. The N-terminal domain forms an α/β structure, in which three α-helices enclose the central β-sheet .
MepB-like superfamily (MepB-like_sf)
Type: Homologous_superfamily

In Staphylococcus aureus MepB is encoded by the MepRAB operon. This operon has been shown to play a role in drug resistance and, although the functions of MepR and MapA are known, there is still little information regarding MepB's function. Structural studies have shown that this protein is structural similar to the PD-(D/E)XK family of endonucleases, although PD-(D/E)XK's catalytic active site residues are not conserved in MepB. MepB binds DNA and RNA, with a higher affinity for RNA and single stranded DNA than for double stranded DNA. The association of MepB with this drug resistance operon suggests that this protein is involved in antimicrobial response, role which is believed to be carried out through its interactions with nucleic acids .
PknH-like extracellular domain superfamily (PknH-like_Extracell_sf)
Type: Homologous_superfamily

This superfamily represents the C-terminal extracellular sensor domain of a group of protein kinases found mainly in Mycobacteria, such as PknH . The PknH sensor domain contains six α helices and seven anti-parallel β strands . It is also found in isolation in numerous proteins, for example the lipoproteins lpqQ, lppH and lpqA from Mycobacterium tuberculosis. It contains two completely conserved C residues that are likely to form a disulphide bond. A second pair of cysteines are less well conserved and probably form a second disulphide bond.
Colicin D/E5 nuclease domain superfamily (Colicin_D/E5_nuclease)
Type: Homologous_superfamily

Colicin is a protein produced by bacteria with Col plasmids. Its function is to attack Escherichia coli through actions on its inner membrane ion channels or through ribonuclease or deoxyribonuclease actions. The C-terminal domain is the ribonuclease domain. Colicin E5 specifically cleaves tRNA anticodons which recognise codons in the form NAY (N:any nucleotide, A:adenosine, Y:pyrimidine) which corresponds to tyrosine, histidine, asparagine and aspartic acid . Colicin D kills target cells by cleaving tRNA(Arg) .
Colicin E5 ribonuclease domain superfamily (Colicin_E5_C_sf)
Type: Homologous_superfamily

Colicin is a protein produced by bacteria with Col plasmids. Its function is to attack Escherichia coli through actions on its inner membrane ion channels or through ribonuclease or deoxyribonuclease actions. The C-terminal domain is the ribonuclease domain. Colicin E5 specifically cleaves tRNA anticodons which recognise codons in the form NAY (N:any nucleotide, A:adenosine, Y:pyrimidine) which corresponds to tyrosine, histidine, asparagine and aspartic acid .
Respiratory growth induced protein 1 superfamily (RGI1_sf)
Type: Homologous_superfamily

This superfamily of fungal proteins includes RGI1, standing for respiratory growth induced 1. RGI1 is involved in aerobic energetic metabolism .
GlpG peptidase, N-terminal domain superfamily (GlpG_N_sf)
Type: Homologous_superfamily

This superfamily represents the N-terminal cytoplasmic domain of the rhomboid intra-membraneous serine protease GlpG, otherwise known as peptidase S54. It is not clear exactly what the function of this domain is in the protease, but its presence is critical for maintaining a catalytically competent state for the protein .

The tertiary structure of the GlpG protein from Escherichia coli has been determined . The GlpG protein has six transmembrane domains (other members of the family are predicted to have seven), with the N- and C-terminal ends anchored in the cytoplasm. One transmembrane domain is shorter than the rest, creating an internal, aqueous cavity just below the membrane surface and it is here were proteolysis occurs. There is also a membrane-embedded loop between the first and second transmembrane domains which is postulated to act as a gate controlling substrate access to the active site.
Small ribosomal subunit protein eS4, central domain superfamily (Ribosomal_eS4_central_sf)
Type: Homologous_superfamily

A number of eukaryotic and archaeal ribosomal proteins can be grouped on the basis of sequence similarities. One of these families includes Small ribosomal subunit protein eS4 from yeast (also known as S7/YS6); archaeal eS4; and mammalian and plant cytoplasmic eS4 . Two highly similar isoforms of mammalian eS4 exist, one coded by a gene on chromosome Y, and the other on chromosome X. These proteins have 233 to 264 amino acids.

This entry represents the central domain of these proteins.
Clp1, C-terminal domain superfamily (Clp1_C_sf)
Type: Homologous_superfamily

The yeast Clp1 is a subunit of cleavage factor IA (CF IA) and is involved in mRNA cleavage and polyadenylation . Clp1 also mediates interactions between CF IA and another complex of the yeast mRNA cleavage and polyadenylation machinery, the Cleavage-Polyadenylation Factor (CPF) . It seems that human Clp1 and yeast Clp1 are not functional orthologues . Human Clp1, and its archeal homologue , but not yeast Clp1, are 5'-OH polynucleotide kinases. In humans Clp1 functions as a RNA kinase important in tRNA splicing , and is also implicated in mRNA and siRNA maturation .

Clp1 contains three domains, a small N-terminal β sandwich domain, a C-terminal domain containing a novel α/β-fold and a central domain that binds ATP . This entry represents the Clp1 C-terminal domain superfamily.
Clp1, N-terminal domain superfamily (Clp1_N_sf)
Type: Homologous_superfamily

Clp1 function involves some degree of adenine or guanine nucleotide binding and participates in the 3' end processing of mRNAs in eukaryotes . Both human Clp1 (hsClp1) and Saccharomyces cerevisiae Clp1 (scClp1) were identified as components of the pre-mRNA 3end-processing machinery. Whereas hsClp1 was shown to also be part of the tRNA endonuclease complex, scClp1 exclusively contributes to mRNA maturation and appears to be enzymatically inactive.

Clp1 contains three domains, a small N-terminal β-sandwich domain, a C-terminal domain containing a novel α/β-fold and a central domain that binds ATP . This entry represents the N-terminal domain involved in DNA binding .
Stn1, C-terminal domain superfamily (Stn1_C_sf)
Type: Homologous_superfamily

Stn1 and Ten1 are DNA-binding proteins with specificity for telomeric DNA substrates and both protect chromosome termini from unregulated resection and regulate telomere length. Stn1 complexes with Ten1 and Cdc13 to function as a telomere-specific replication protein A (RPA)-like complex . These three interacting proteins associate with the telomeric overhang in budding yeast, whereas a single protein known as Pot1 (protection of telomeres-1) performs this function in fission yeast. Two separate protein complexes are required for chromosome end protection in fission yeast while a two-subunit complex consisting of POT1 and TPP1 associates with telomeric ssDNA in humans. Protection of telomeres by multiple proteins with OB-fold domains is conserved in eukaryotic evolution .

This entry represents the C-terminal domain of Stn1 and consists of tandem winged helix-turn-helix motifs .
Endoribonuclease antitoxin GhoS superfamily (GhoS_sf)
Type: Homologous_superfamily

GhoS is part of the GhoT-GhoS type V toxin-antitoxin (TA) system. GhoT is inhibited by antitoxin GhoS, which specifically cleaves its mRNA .
CRISPR-Cas system, Cmr2 subunit, D1 domain, cysteine cluster (Cmr2_N)
Type: Homologous_superfamily

Cmr2 is a subunit of a CRISPR RNA-Cas protein complex (the Cmr complex, consisting of subunits Cmr1-6), that cleaves foreign RNA in prokaryotes. Its N-terminal region is a putative HD (histidine-aspartate) nuclease domain; however, it does not participate in target RNA cleavage . In fact, Cmr4 has been identified as the conserved endoribonuclease of the Cmr complex . In Pyrococcus furiosus, the HD domain of Cmr2 is formed by eight α-helices and a β-hairpin, and lies diametrically opposite to Cmr3 .

The N-terminal domain D1 contains a ferredoxin-like fold (which contains a P-loop) and a cysteine cluster that is formed by two CXXC motifs. It is the largest of the four domains of Cmr2 and is composed of nine helices and three β-strands. ADP binds near the P-loop region of the D1 domain. The D1 domain that constitutes one face of the active site pocket might fulfil the role of fingers domain (similarly to DNA polymerases) in binding the nucleotide .
Spidroin, N-terminal domain superfamily (Spidroin_N_sf)
Type: Homologous_superfamily

Spidroin is produced by a number of arachnids. Spidrions are made up of repetitive segments flanked by conserved non-repetitive domains, and this domain is the conserved non-repetitive region. Aggregation to form the rigid silk occurs due to association at the repetitive regions, and the N-terminal domain is necessary to prevent premature aggregation during storage before extrusion. This N-terminal region inhibits precocious aggregation and then accelerates and directs self-assembly as the pH is lowered along the extrusion duct .
Rhomboid protease, N-terminal domain superfamily (NRho_sf)
Type: Homologous_superfamily

Rhomboids are integral membrane proteases that release cellular signals from membrane-bound substrates through a general signal transduction mechanism known as regulated intramembrane proteolysis (RIP).

This entry represents the N-terminal cytosolic domain of rhomboid intramembrane proteases from Pseudomonas. This domain, known as NRho, consists of a novel α/β fold and displays a strong and specific association with micelles of the zwitterionic lysophospholipid-analogue C16PN .
MogR, DNA-binding domain superfamily (MogR_DNA-bd_sf)
Type: Homologous_superfamily

This domain superfamily is found in bacteria, and is approximately 150 amino acids in length. MogR is involved in the transcriptional repressor of flagellar motility genes, such as flaA, during extracellular growth at 37 degrees Celsius and during intracellular infection. It binds directly to gene promoter region and probably prevents RNA polymerase binding. At low temperatures, MogR repression activity is modulated by the DegU response regulator in an unknown mechanism. MogR is required for full virulence .

MogR binds AT rich flagellar gene promoter regions upstream of the flagellar gene. These regions follow the pattern 5'-TTTTNNNNNAAAA-3'. This superfamily represents the N-terminal DNA binding domain of MogR .
Phi-29-like late genes activator superfamily (Phi-29-like_sf)
Type: Homologous_superfamily

This superfamily consists of phi-29-like late genes activator (or early protein GP4). This protein is thought to be a positive regulator of late transcription and may function as a sigma-like component of the host RNA polymerase .
Jag, N-terminal domain superfamily (Jag_N_dom_sf)
Type: Homologous_superfamily

This entry includes the RNA-binding protein KhpB, also known as RNA-binding protein Jag/EloR, a RNA chaperone that forms a complex with KhpA and binds to cellular RNA, controlling its expression. It plays a role in peptidoglycan (PG) homeostasis and cell length regulation, cell division and maintenance of cell shape . Bacillus subtilis KhpB/Jag is associated with SpoIIIJ, a gene necessary for the third stage of sporulation . This domain is found at the N terminus of the KhpB/Jag proteins, whose function is unknown.
Dicer dimerisation domain superfamily (Dicer_dimer_sf)
Type: Homologous_superfamily

This entry represents the dimerisation domain in Dicer. It is essential for the activity of Dicer . It is a divergent double-stranded RNA-binding domain . The N-terminal α helix of this domain is in a different orientation to that found in canonical dsRNA-binding domains. This results in a change of charge distribution at the potential dsRNA-binding surface and in the N- and C-terminal of the domain being nearby . This domain has weak dsRNA-binding activity. It mediates heterodimerisation of Dicer proteins with their respective protein partners .
DNA polymerase III, tau subunit, domain V superfamily (PolIII_tau_V_sf)
Type: Homologous_superfamily

This superfamily represents a domain found at the C terminus of DNA polymerase III subunit tau. The extreme C-terminal region of this domain interacts with the alpha subunit of the DNA polymerase III holoenzyme .
TGT, patch-forming C2 domain superfamily (TGT_C2_sf)
Type: Homologous_superfamily

Archaeosine tRNA-guanine transglycosylase (ArcTGT) is made of an N-terminal catalytic domain and a C-terminal region with unidentified functions. The C-terminal region is divided into three domains, C1, C2, and C3. The catalytic domain of TGT has conserved basic residues on the outer surface of the N-terminal three-stranded β sheet, which closes the barrel. It is postulated that these basic residues from the three domains form a continuous, positively charged patch to which the tRNA binds .

This superfamily represents domain C2 of ArcTGT, formed by a four-stranded anti-parallel β-sheet lined with two α helices. It has conserved basic residues on the surface of the β-sheets as does the C-terminal domain PUA (

) .
PdxB, dimerisation domain superfamily (PdxB_dimer_sf)
Type: Homologous_superfamily

This entry represents the dimerisation domain found at the C-terminal of erythronate-4-phosphate dehydrogenase (PdxB) .
Ubiquitin-activating enzyme E1, C-terminal domain superfamily (UBA_E1_C_sf)
Type: Homologous_superfamily

This domain is found at the C terminus of Ubiquitin-activating enzyme E1 proteins. It binds to E2 enzymes .
SRP68, N-terminal domain superfamily (SRP68_N_sf)
Type: Homologous_superfamily

Signal recognition particles (SRPs) are ribonucleoprotein complexes that target particular nascent pre-secretory proteins to the endoplasmic reticulum. The SRP complex targets the ribosome-nascent chain complex to the SRP receptor (SR), which is anchored in the ER, where SR compaction and GTPase rearrangement drive cotranslational protein translocation into the ER . SRP68 is one of the two largest proteins found in SRPs (the other being SRP72), and it forms a heterodimer with SRP72. Heterodimer formation is essential for SRP function . SRP68 binds to SRP RNA directly, while SRP72 binds the SRP RNA largely via nonspecific electrostatic interaction. The binding of SRP72 with SRP RNA enhances the affinity of SRP68 for the RNA. This entry describes the N-terminal RNA-binding domain (RBD) of SRP68, a tetratricopeptide-like module. Interactions between SRP68-RBD and SRP RNA (7SL RNA) are thought to facilitate a conformation of SRP RNA that is required for interactions with ribosomal RNA .
DNA/RNA-binding protein KIN17, WH-like domain superfamily (KIN17_WH-like_sf)
Type: Homologous_superfamily

Kin17 is a highly conserved protein that participates in DNA replication, DNA repair and cell cycle progression .

Region 51-160 of human Kin17 folds into an atypical winged helix (WH) domain. It consists of a three-α-helix bundle packed against a three-stranded β-sheet. Structural comparison with analogous WH domains reveals that Kin17 WH module presents an additional helix. In addition, helix H3 is not positively charged as in classical DNA-binding WH domains . This domain may be involved in protein-protein interactions.
Phycobilisome linker domain superfamily (PBS_linker_sf)
Type: Homologous_superfamily

Phycobilisomes (PBSs) are the major light-harvesting systems in cyanobacteria and red algae. PBS is a supercomplex that is composed of a core complex and multiple peripheral rod complexes. Typically, the core consists of two or five cylinders lying on the membrane with, in most cases, multiple rods radiating from the core to form a hemidiscoidal structure. The building units of the core cylinders and the peripheral rods are trimeric and hexameric discs, in which a monomer consists of a pair of related phycobiliproteins (PBPs), such as phycorerythrins, phycoerythrocyanins, phycocyanins, and allophycocyanins. The discs are connected to each other via specific linker polypeptides to form peripheral rods or core cylinders. Linker polypeptides share a conserved domain of ~180 residues, which can be present in one or multiple copies .
DNA polymerase alpha, zinc finger domain superfamily (Pol_alpha_znc_sf)
Type: Homologous_superfamily

The DNA Polymerase alpha zinc finger domain adopts an α-helix-like structure, followed by three turns, all of which involve proline. The resulting motif is a helix-turn-helix motif, in contrast to other zinc finger domains, which show anti-parallel sheet and helix conformation. Zinc binding occurs due to the presence of four cysteine residues positioned to bind the metal centre in a tetrahedral coordination geometry. The function of this domain is uncertain: it has been proposed that the zinc finger motif may be an essential part of the DNA binding domain. It is involved in providing a structural platform for interactions with both oligonucleotide/oligosaccharide (OB) and phosphoesterase domains of the B subunit .
CRISPR-associated Cas3-type HD domain superfamily (CRISPR-assoc_Cas3_HD_sf)
Type: Homologous_superfamily

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.

This entry represents the HD domain, which is found in a number of Cas proteins that tend to be found near CRISPR repeats. These domains can be found either separately or as the N-terminal region of Cas3, the helicase-containing CRISPR-associated protein. CRISPR loci appear to be mobile elements with a wide host range. The Cas3-type HD domain has nuclease activity against ssDNA and ssRNA .
Peptidoglycan hydrolase Gp4 superfamily (Gp4_sf)
Type: Homologous_superfamily

The tail complex in bacteriophage P22, and related phages, mediates host cell attachment and DNA injection. Tail assembly is a complex event that is essential for the retention and stabilisation of the newly packaged DNA within the capsid. This process involves the sequential addition of three tail accessory factors (GP4, GP10, GP26) and the adhesion tailspike protein (GP9) to the capsid-bound portal protein .

Gp4 is the first factor to attach after DNA packaging. Twelve monomeric subunits of GP4 bind to the exposed surface of the portal ring, beginning the tail assembly process. GP4 does not physically block the DNA entry/exit channel, but appears to act as a structural adaptor for the other tail accessory factors GP10 and GP26 .

Gp4 has been shown to have peptidoglycan hydrolase activity .
Tmem141 superfamily (Tmem141_sf)
Type: Homologous_superfamily

Members of this superfamily are multi-pass membrane proteins. Their function is not clear.