SII-SWORD/CoKE huggingface dataset:
Copper binding periplasmic protein CusF superfamily (CusF_sf)
Type: Homologous_superfamily

This superfamily represents the periplasmic metallochaperone CusF, a non-essential component of the CusCFBA system that confers copper and silver resistance in E. coli. Although not essential, CusF is required for optimal function .

This entry also matches PilY2 protein.
Choline/Carnitine o-acyltransferase, domain 2 (Cho/carn_acyl_trans_2)
Type: Homologous_superfamily

This superfamily represents the domain 2 of choline/carnitine o-acyltransferase.

Choline and carnitine o-acyltransferase are two evolutionary and structurally related enzymes. These are two different types of acyltransferases, a type of transferase enzymes that transfer an acetyl group. The former, choline O-acyltransferase, is involved choline biosynthesis and it is essential for the development and neuronal activities of cholinergic systems involved in many fundamental brain functions . The latter, carnitine o-acyltransferase, catalyzes the reversible acylation of L-carnitine and thus plays a vital role in fatty acid beta-oxidation and maintenance of acyl coenzyme A (acyl-CoA) pools . Both show a remarkably similar structure, they are monomeric proteins containing two domains (1 and 2) that interconnect to form an active site tunnel .
Cell division protein ZapA, N-terminal (Cell_div_ZapA_N)
Type: Homologous_superfamily

ZapA is a cell division protein which interacts with FtsZ. FtsZ is part of a mid-cell cytokinetic structure termed the Z-ring that recruits a hierarchy of fission related proteins early in the bacterial cell cycle. The interaction of FtsZ with ZapA drives its polymerisation and promotes FtsZ filament bundling thereby contributing to the spatio-temporal tuning of the Z-ring .

The structure of ZapA is organised into two distinct domains, with the first 49 residues forming a globular domain comprised of a two stranded antiparallel β-sheet and an α-helix, whereas the C-terminal half of the protein (residues 50-102) forms a single, 14-turn α-helix. The ZapA protomer forms a pseudosymmetric tetramer.

This superfamily represents a domain found at the N terminus of the cell division protein ZapA. Its structure is composed of an α-helix which plays a role in mediating ZapA-FtsZ interactions to facilitate FtsZ filament bundling and Z-ring stability in dividing bacterial cells.
WD repeat and FYVE domain-containing protein 1/2 (WDFY1/WDFY2)
Type: Family

This entry represents a group of WD repeat and FYVE domain-containing proteins, including WDFY1 and WDFY2. WDFY1 mediates TLR3/4 signalling by recruiting TRIF . WDFY2, also known as Prof (propeller-FYVE protein), is involved in endocytosis .
Zona pellucida, ZP-C domain (ZP-C_dom)
Type: Homologous_superfamily

This superfamily represents the ZP-C domain.

The zona pellucida (ZP) domain is a protein polymerisation module of ~260 amino acid module, which is found at the C terminus of many secreted eukaryotic glycoproteins that play fundamental roles in development, hearing, immunity, and cancer .

The ZP module is not only conserved in egg coat components but is also found in many other secreted eukaryotic proteins with variable architecture and biological function. It is responsible for the incorporation of ZP3 and other subunits into the ZP and consists of two domains, ZP-N and ZP-C, that are separated by a protease-sensitive linker. Whereas ZP-N is thought to constitute a basic building block of ZP filaments, ZP-C may mediate the specificity of interaction between subunits. These processes are controlled by an external hydrophobic patch (EHP) contained within the C-terminal propeptide of ZP component precursors and an internal hydrophobic patch (IHP) inside the ZP module.
Phosphoinositide 3-kinase, accessory (PIK) domain superfamily (PI3K_accessory_sf)
Type: Homologous_superfamily

Phosphatidylinositol 3-kinase (PI3K) (

) is an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring. The role of the accessory domain of phosphoinositide 3-kinase (PI3-kinase) is unclear. It may be involved in substrate presentation .

PI3Ks fall into three classes based on their primary structure and substrate specificity. The class I PI3Ks can use phosphatidylinositol 4,5-bisphosphate (PIP2) as a substrate to generate the second messenger PIP3 and act as transducers downstream of tyrosine kinase receptors and G protein-coupled receptors. PI3Ks are involved in a large number of fundamental cellular processes, including apoptosis, proliferation, cell motility, and adhesion. The 3-phosphorylated phospholipids generated by PI3Ks act as membrane tethers for proteins such as protein kinase B (PKB) and phospholipid-dependent kinase 1 (PDK1). These are important components of the molecular mechanisms of diseases such as diabetes, cancer, and chronic inflammation. The class I isozymes are subdivided into classes IA and IB, with each subtype having a different regulatory subunit. The class IA enzymes (alpha, beta, and delta) have a p85 regulatory subunit containing two SH2 domains, which are essential for their activation by tyrosine kinase receptors. The class IB PI3K gamma has a p101 subunit, which is required for maximal G-beta-gamma-stimulated formation of PIP3 .
Putative peptidyl-tRNA hydrolase PTRHD1 (PTRHD1)
Type: Family

PTRHD1 is predicted to be peptidyl-tRNA hydrolase due to their amino acid sequence similarity. However, its real function is still not clear. Mutations in PTRHD1 cause autosomal-recessive juvenile parkinsonism and intellectual disability .
DNA excision repair protein Rad28/ERCC8/Ckn1/ATCSA-1 (Rad28/ERCC8/Ckn1/ATCSA-1)
Type: Family

This entry represents a group of DNA excision repair proteins, including Rad28 from budding yeasts , Ckn1 from fission yeasts, ATCSA-1 from Arabidopsis and ERCC8 (also known as CSA) from animals . Ckn1 is involved in transcription-coupled nucleotide excision repair . Human CSA is part of a E3-ubiquitin ligase (E3-ub ligase) complex and plays an important part in transcription-coupled repair (TCR). In Arabidopsis, ATCSA-1 is a critical component for initiating the repair of UV-B-induced DNA lesions .

Mutations in the CSA gene cause Cockayne syndrome A (CSA), a rare disorder characterised by cutaneous sensitivity to sunlight, abnormal and slow growth, cachectic dwarfism, progeroid appearance, progressive pigmentary retinopathy and sensorineural deafness .
Nop, C-terminal domain (Nop_C)
Type: Homologous_superfamily

The Nop domain is present in various pre-RNA processing ribonucleoproteins (RNP):

Eukaryotic Prp31, part of a tri-snRNP complex. It is involved in pre-mRNA splicing.

Eukaryotic Nucleolar proteins 56 and 58 (Nop56 and Nop58), components of box C/D small nucleolar ribonucleoprotein (snoRNP) particles.

Archaeal Nop5, an homologue of Nop56/Nop58.

The Nop domain is a RNP binding module, exhibiting RNA and protein binding surfaces. It is oval-shaped and exclusively α-helical .

This entry represents the C-terminal part of the Nop domain.
CHASE domain superfamily (CHASE_sf)
Type: Homologous_superfamily

The CHASE domain is an extracellular domain of 200-230 amino acids, which is found in transmembrane receptors from bacteria, lower eukaryotes and plants. It has been named CHASE (Cyclases/Histidine Kinases Associated Sensory Extracellular) because of its presence in diverse receptor-like proteins with histidine kinase and nucleotide cyclase domains. It is found at the N-terminal in extracellular or periplasmic locations, followed by an intracellular tail housing diverse enzymatic signalling domains such as histidine kinase (

), adenyl cyclase, GGDEF-type nucleotide cyclase, and EAL-type phosphodiesterase domains, as well as non-enzymatic domains such as PAS (

), GAF (

), phosphohistidine, and response regulatory domains. This domain is predicted to bind diverse low molecular weight ligands, such as cytokinin-like adenine derivatives or peptides, and mediate signal transduction through the respective receptors . It has a predicted α+β fold, with two extended α helices on both boundaries and two central α helices separated by β sheets. The N-terminal and C-terminal regions are less conserved compared with the central part of the domain, which shows strongly conserved motifs.
Gamma-tubulin complex component, C-terminal domain superfamily (GCP_C_sf)
Type: Homologous_superfamily

This superfamily covers families of proteins all derived via gene-duplication events that act together in the gamma-tubulin complex. This complex is required for microtubule nucleation at the centrosome. The C-terminal domain is involved in the binding of gamma-tubulin, demonstrated by in vitro and deletion experiments with GCP4 (gamma-tubulin complex protein 4) .
Recombination protein O, C-terminal (RecO_C)
Type: Homologous_superfamily

Structural domains which comprise this superfamily share the structure of the C-terminal domain (CTD) of the bacterial recombination protein O (RecO), which belongs to the RecF recombination repair pathway involved in replication recovery after DNA damage. It is believed that this CTD acts a a structural scaffold to keep the N-terminal and Zinc-binding domains together. However, because it forms a positively charged grooved with NTD, it is also thought to be involved in DNA binding .
HypD, domain 1 (HypD_1)
Type: Homologous_superfamily

HypD is involved in the hyp operon which is needed for the activity of the three hydrogenase isoenzymes in Escherichia coli. HypD is one of the genes needed for formation of these enzymes . This protein has been found in Gram-negative and Gram-positive bacteria and Archaea. HypD contains many possible metal binding residues, which may bind to nickel. Transposon insertions into HypD resulted in Rhizobium leguminosarum mutants that lacked any hydrogenase activity in symbiosis with peas .

This superfamily represents the Hydrogenase formation protein HypD domain 1. This domain, known as α/β domain 1 which together with α/β domain 2, make up a cleft to allow for the assembly of the Fe-S cluster binding domain.
HypD, domain 2 (HypD_2_sf)
Type: Homologous_superfamily

HypD is involved in the hyp operon which is needed for the activity of the three hydrogenase isoenzymes in Escherichia coli. HypD is one of the genes needed for formation of these enzymes . This protein has been found in Gram-negative and Gram-positive bacteria and Archaea. HypD contains many possible metal binding residues, which may bind to nickel. Transposon insertions into HypD resulted in Rhizobium leguminosarum mutants that lacked any hydrogenase activity in symbiosis with peas .

This superfamily represents the Hydrogenase formation protein HypD domain 2. Together with HypD domain 1, it makes up a cleft allowing the assembly of the Fe-S cluster binding domain.
Tgt2/MlaC superfamily (Tgt2/MlaC_sf)
Type: Homologous_superfamily

This superfamily includes toluene tolerance protein Ttg2 and intermembrane phospholipid transport system binding protein MlaC.

MlaC is a component of the Mla pathway, an ABC transport system that functions to maintain the asymmetry of the outer membrane. These proteins are involved in toluene tolerance, which is mediated by increased cell membrane rigidity resulting from changes in fatty acid and phospholipid compositions, exclusion of toluene from the cell membrane, and removal of intracellular toluene by degradation . Ttg2 is one of the many proteins involved in these processes .

MlaC actively prevents phospholipid accumulation at the cell surface. It probably maintains lipid asymmetry in the outer membrane by retrograde trafficking of phospholipids from the outer membrane to the inner membrane. It may transfer phospholipids across the periplasmic space and deliver them to the mlaFEDB complex at the inner membrane .
Zinc finger CCHC domain-containing protein 9 (ZCCHC9)
Type: Family

The function of the Zinc finger CCHC domain-containing protein 9 (ZCCHC9) is not clear. In humans, it suppresses the transcription activities of NF-kappa B and SRE, and may play roles in the Mitogen-Activated Protein Kinase (MAPK) signalling transduction pathway .
T-cell leukemia homeobox protein 1/2/3 (TLX1/2/3)
Type: Family

This entry represents a group of homeobox proteins, including Tlx1/2/3. They are transcription factors that belong to the to the Hox11 family. In general, they bind to the DNA sequence 5'-CGGTAATTGG-3' . Tlx1 and Tlx3 are required for fate determination of glutamatergic and GABAergic neurons in the dorsal spinal cord . Tlx1, also known as Hox11, is required to maintain normal Wt1 mRNA levels in the developing spleen in mice . Tlx2, also known as Ncx/Hox11L.1, is required for the adequate development of enteric neurons in mice .
Ethanolamine ammonia-lyase light chain, C-terminal (EutC_C)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain of several bacterial ethanolamine ammonia-lyase light chain (EutC) sequences. Ethanolamine ammonia-lyase is a bacterial enzyme that catalyses the adenosylcobalamin-dependent conversion of certain vicinal amino alcohols to oxo compounds and ammonia .
MtfA, N-terminal (MtfA_N)
Type: Homologous_superfamily

Mlc titration factor A (MtfA, previously known as YeeI) is a transcription factor A that binds Mlc (make large colonies), itself a repressor of glucose and hence a protein important in regulation of the phosphoenolpyruvate:glucose-phosphotransferase (ptsG) system, the major glucose transporter in E. coli. Mlc is a repressor of ptsG, and MtfA is found to bind and inactivate Mlc with high affinity . The membrane-bound protein EIICBGlc encoded by the ptsG gene is the major glucose transporter in Escherichia coli. MtfA is found to be a glucose-regulated peptidase , whose activity is regulated by binding to Mlc available in the cytoplasm, which in turn has been released from EIICBGlc during times when no glucose is taken up. A physiologically relevant target for this peptidase is not yet known.

The N-terminal domain of MtfA adopts a mixed α/β structure, with four α-helices, three 310-helices, and three parallel β-strands. The C-terminal domain has an all-helical structure .

This superfamily represents the N-terminal domain found in MtfA.
2,3-bisphosphoglycerate-independent phosphoglycerate mutase superfamily (Pglycerate_mutase_ApgM_sf)
Type: Homologous_superfamily

This superfamily represents domain found in 2,3-bisphosphoglycerate-independent phosphoglycerate mutase (iPGAM), it is a metalloenzyme found particularly in archaea and some eubacteria. It is responsible for the interconversion of 2-phosphoglycerate and 3-phosphoglycerate . It is distantly related to the iPGAM (

) characteristic of plants and many eubacteria. The common active site and metal-binding residues of the phosphatase domain are easily identified, but the putative phosphotransferase domain is highly diverged. These proteins are unrelated to the cofactor-dependent PGAM. Activity has been demonstrated for proteins from Methanocaldococcus jannaschii (Methanococcus jannaschii) , Pyrococcus furiosus , and Sulfolobus solfataricus . These proteins were initially misidentified as phosphonopyruvate decarboxylase.
Ethanolamine ammonia-lyase light chain, N-terminal (EutC_N)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain of several bacterial ethanolamine ammonia-lyase light chain (EutC) sequences. Ethanolamine ammonia-lyase is a bacterial enzyme that catalyses the adenosylcobalamin-dependent conversion of certain vicinal amino alcohols to oxo compounds and ammonia .
2-keto-3-deoxy-galactonokinase, C-terminal domain (DGOK_C)
Type: Homologous_superfamily

2-keto-3-deoxy-galactonokinase is a bacterial transferase which catalyses the penultimate reaction in the Ley-Doudoroff pathway, where d-galactose is metabolized into pyruvate and d-glyceraldehyde 3-phosphate. This reaction involves the phosphorylation of 2-oxo-3-deoxygalactonate to 2-oxo-3-deoxygalactonate 6-phosphate using ATP as a phosphoryl-group donor.

This superfamily represents the C-terminal domain of 2-keto-3-deoxy-galactonokinase. This domain contains a nucleotide biding site .
2-keto-3-deoxy-galactonokinase, N-terminal (DGOK_N)
Type: Homologous_superfamily

2-keto-3-deoxy-galactonokinase is a bacterial transferase which catalyses the penultimate reaction in the Ley-Doudoroff pathway, where d-galactose is metabolized into pyruvate and d-glyceraldehyde 3-phosphate. This reaction involves the phosphorylation of 2-oxo-3-deoxygalactonate to 2-oxo-3-deoxygalactonate 6-phosphate using ATP as a phosphoryl-group donor.

This superfamily represents the N-terminal domain of 2-keto-3-deoxy-galactonokinase. The structure characterisation of this enzyme reveals a putative substrate-binding site, shown to be generated mostly by the N-terminal domain .
RACo-like, middle domain superfamily (Raco-like_middle_sf)
Type: Homologous_superfamily

This superfamily represents the middle domain of the reductive activator of CoFeSP (RACo) proteins (

). This region contains residues in their α-helices (H6 and H7) that mediate dimerization with subdomain I of the C-terminal domain. Structure analysis of RACo indicate that it contains 4 regions: N-terminal region (residues 3-94) binding the [2Fe-2S] cluster, a linker region (residues 95-125), the middle region (residues 126-206), and the large C-terminal domain (residues 207-630) .
Lsr2-like, dimerization domain (Lsr2-like_dimerization)
Type: Homologous_superfamily

This superfamily represents the N-terminal dimerization domain of the Lsr2 protein, a bacterial nucleoid-associated protein involved in chromosome organization and global gene regulation. This protein binds AT-rich regions of the genome, including genomic islands acquired by horizontal gene transfer and regions encoding major virulence factors, such as the ESX secretion systems, the lipid virulence factors PDIM and PGL, and the PE/PPE families of antigenic proteins. Lsr2 has an N-terminal dimerization domain and a C-terminal DNA-binding domain. Besides enabling dimerization of Lsr2 monomers, structural studies on the N-terminal domain have shown that Lsr2 dimers show a self-associative propensity allowing chromosome compaction and gene regulation in response to external stress .
Nitrile hydratase beta subunit, N-terminal (CN_hydtase_beta_C)
Type: Homologous_superfamily

Nitrile hydratases (

) are unusual metalloenzymes that catalyse the hydration of nitriles to their corresponding amides. They are used as biocatalysts in acrylamide production, one of the few commercial scale bioprocesses, as well as in environmental remediation for the removal of nitriles from waste streams. Nitrile hydratases are composed of two subunits, alpha and beta, and they contain one iron atom per alpha beta unit .

This entry represents the N-terminal domain of nitrile hydratase beta subunit which contains an irregular array of helices.
Diphthamide synthesis DPH1/DPH2, domain 1 (DPH1/DPH2_1)
Type: Homologous_superfamily

Diphthamide is the name given to a unique post-translationally modified histidine residue in archaeal and eukaryotic translation elongation factor 2. This modified histidine is target of diphtheria toxin, which inhibits eukaryotic protein synthesis by ADP-ribosylating diphthamide in EF2 .

The diphthamide synthesis DPH1/DPH2 enzymes which catalyse the first step in diphthamide biosynthesis. Archaeal DPHs are more similar to eukaryotic DPH1 than to DPH2 .

Available structural information on PhDph2 reveals that this enzyme is a homodimer and that each monomer comprises three domains which share the same overall fold. The basic domain fold is a four-stranded parallel β-sheet with three flanking α-helices (or two α-helices and one 3(10) helix in the case of domain 2). The two β-sheets in domain 1 and 2 each contain an additional β-strand that is antiparallel to the rest of the β-sheet. Domains 2 and 3 have two additional α-helices. Domain 1 of one monomer and domain 3 of the adjacent monomer form the dimer interface, creating an extended nine-stranded β-sheet. The domain folds and their arrangement resemble the structure of quinolinate synthase but the orientations of the domains with respect to each other are different in the two enzymes. Three conserved cysteine residues (Cys59, Cys163 and Cys287), each coming from a different structural domain, are clustered together in the centre of the PhDph2 monomers. All three cysteine residues are conserved in eukaryotic DPH1s. The first and third cysteine residues are conserved in eukaryotic DPH2s .

This superfamily represents the domain 1 found in diphthamide synthesis DPH1/DPH2 enzymes.
Diphthamide synthesis DPH1/DPH2, domain 2 (DPH1/DPH2_2)
Type: Homologous_superfamily

Diphthamide is the name given to a unique post-translationally modified histidine residue in archaeal and eukaryotic translation elongation factor 2. This modified histidine is target of diphtheria toxin, which inhibits eukaryotic protein synthesis by ADP-ribosylating diphthamide in EF2 .

The diphthamide synthesis DPH1/DPH2 enzymes which catalyse the first step in diphthamide biosynthesis. Archaeal DPHs are more similar to eukaryotic DPH1 than to DPH2 .

Available structural information on PhDph2 reveals that this enzyme is a homodimer and that each monomer comprises three domains which share the same overall fold. The basic domain fold is a four-stranded parallel β-sheet with three flanking α-helices (or two α-helices and one 3(10) helix in the case of domain 2). The two β-sheets in domain 1 and 2 each contain an additional β-strand that is antiparallel to the rest of the β-sheet. Domains 2 and 3 have two additional α-helices. Domain 1 of one monomer and domain 3 of the adjacent monomer form the dimer interface, creating an extended nine-stranded β-sheet. The domain folds and their arrangement resemble the structure of quinolinate synthase but the orientations of the domains with respect to each other are different in the two enzymes. Three conserved cysteine residues (Cys59, Cys163 and Cys287), each coming from a different structural domain, are clustered together in the centre of the PhDph2 monomers. All three cysteine residues are conserved in eukaryotic DPH1s. The first and third cysteine residues are conserved in eukaryotic DPH2s .

This superfamily represents the domain 2 found in diphthamide synthesis DPH1/DPH2 enzymes.
Diphthamide synthesis DPH1/DPH2, domain 3 (DPH1/DPH2_3)
Type: Homologous_superfamily

Diphthamide is the name given to a unique post-translationally modified histidine residue in archaeal and eukaryotic translation elongation factor 2. This modified histidine is target of diphtheria toxin, which inhibits eukaryotic protein synthesis by ADP-ribosylating diphthamide in EF2 .

The diphthamide synthesis DPH1/DPH2 enzymes which catalyse the first step in diphthamide biosynthesis. Archaeal DPHs are more similar to eukaryotic DPH1 than to DPH2 .

Available structural information on PhDph2 reveals that this enzyme is a homodimer and that each monomer comprises three domains which share the same overall fold. The basic domain fold is a four-stranded parallel β-sheet with three flanking α-helices (or two α-helices and one 3(10) helix in the case of domain 2). The two β-sheets in domain 1 and 2 each contain an additional β-strand that is antiparallel to the rest of the β-sheet. Domains 2 and 3 have two additional α-helices. Domain 1 of one monomer and domain 3 of the adjacent monomer form the dimer interface, creating an extended nine-stranded β-sheet. The domain folds and their arrangement resemble the structure of quinolinate synthase but the orientations of the domains with respect to each other are different in the two enzymes. Three conserved cysteine residues (Cys59, Cys163 and Cys287), each coming from a different structural domain, are clustered together in the centre of the PhDph2 monomers. All three cysteine residues are conserved in eukaryotic DPH1s. The first and third cysteine residues are conserved in eukaryotic DPH2s .

This superfamily represents the domain 3 found in diphthamide synthesis DPH1/DPH2 enzymes.
PPPDE peptidase domain superfamily (PPPDE_sf)
Type: Homologous_superfamily

This superfamily represents the PPPDE domain (Permuted Papain fold Peptidases of DsRNA viruses and Eukaryotes). It consists of predicted thiol peptidases with a circularly permuted papain-like fold .