SII-SWORD/CoKE huggingface dataset:
Immunity protein 63 (Imm63)
Type: Domain

Polymorphic toxins systems consist of secreted toxins, primarily involved in intra-specific conflict between related strains of prokaryotes. These toxins are as a rule multi-domain and tend to vary their toxin domains through a process of recombination that might replace an existing toxin domain by a distinct one encoded by standalone cassettes, therefore their name as polymorphic toxins. A key feature that distinguishes the polymorphic toxins from conventional toxins (whose primary targets are in distantly related organisms) is the presence of immunity proteins.

This entry represents a predicted immunity protein with an α+β fold and a conserved E+G and ExxY motifs. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, which usually contains toxin domains of the Ntox40, Tox-CdiAC and Tox-ARC families . The protein is also found in polyimmunity loci in polymorphic toxin systems.
Immunity protein IFT-like (Imm_IFT-like)
Type: Family

This entry represents immunity proteins with an α+β fold and a conserved arginine. The family includes immunity factor for TNT (IFT) from Mycobacterium tuberculosis. This bacteria uses tuberculosis necrotizing toxin (TNT) to kill human macrophages; the immunity factor IFT binds TNT and inhibits its activity to prevent self-poisoning .
Immunity protein 59 (Imm59)
Type: Family

This entry represents a predicted immunity protein with an α+β fold and a conserved [DE]R motif. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, which usually contains toxin domains of the Ntox13 or Ntox40 families . In some proteins this domain is fused to the Imm38 (

) immunity domain.
Immunity protein 57 (Imm57)
Type: Family

This entry represents a predicted immunity protein with a mostly α-helical fold and conserved aspartate and cysteine residues and an SE motif. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the LD-peptidase or Tox-Caspase families .
Immunity protein 51 (Imm51)
Type: Family

This entry represents a predicted immunity protein with an α+β fold and a conserved tryptophan and Dx[DE] motif. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Tox-RES or Tox-URI1 families. Proteins containing this domain are present in heterogeneous polyimmunity loci in polymorphic toxin systems .
Immunity protein 50 (Imm50)
Type: Family

This entry represents a predicted immunity protein with an all-β fold. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Tox-HHH or Ntox24 families .
Immunity protein 42 (Imm42)
Type: Family

This entry represents a predicted immunity protein with an α+β fold. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Ntox18 family .
Immunity protein 41 (Imm41)
Type: Family

This entry represents a predicted immunity protein with an α+β fold and a conserved SF motif and tryptophan residue. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Ntox21, Ntox29 or Tox-ART-RSE-like ADP-ribosyltransferase families .
Immunity protein 27 (Imm27)
Type: Family

This entry represents a predicted immunity protein with an α+β fold and a conserved aspartate and GGxP motif. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Ntox10 or Tox-ParB families .
Immunity protein 21 (Imm21)
Type: Family

This entry represents a predicted immunity protein with an α+β fold and conserved WxG and YxxxC motif. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the NGO1392-family of HNH/Endonuclease VII fold nucleases .
Immunity protein 10 (Imm10)
Type: Family

This entry represents a predicted immunity protein with a mostly all-β fold and a conserved arginine residue. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a Pput_2613 deaminase domain . The protein is also found in heterogeneous polyimmunity loci.
Immunity protein 9 (Imm9)
Type: Family

This entry represents a predicted immunity protein with an α+β fold and a conserved lysine residue. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Tox-URI2 family . The protein is also found in heterogeneous polyimmunity loci.
Immunity protein 8 (Imm8)
Type: Family

This entry represents a predicted immunity protein with an α+β fold and a conserved Wea (a: aromatic) motif. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Ntox7 family .
Immunity protein 7 (Imm7)
Type: Family

This entry represents a predicted immunity protein with an α+β fold and a conserved GxaG motif. They are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a Tox-REase-3 domain .
Immunity protein 72 (Imm72)
Type: Domain

This entry represents a predicted immunity protein with a mostly all-β fold and GxxE, WxDxRY motifs and a glutamate residue. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, which usually contains toxin domains of the Ntox48 family. This domain is often fused to the Imm71 immunity domain .
Immunity protein 65 (Imm65)
Type: Family

This entry represents a predicted immunity protein with an α+β fold and a conserved YxC motif. They are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, which usually contains toxin domains of the Tox-JAB1 family . The immunity protein typically contains a signal peptide and a lipobox.
Immunity protein 58 (Imm58)
Type: Family

This entry represents a predicted immunity protein with an α+β fold and YxxxD, WxG, KxxxE motifs. They are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene .

Polymorphic toxins systems consist of secreted toxins, primarily involved in intra-specific conflict between related strains of prokaryotes. These toxins are as a rule multi-domain and tend to vary their toxin domains through a process of recombination that might replace an existing toxin domain by a distinct one encoded by standalone cassettes, therefore their name as polymorphic toxins. A key feature that distinguishes the polymorphic toxins from conventional toxins (whose primary targets are in distantly related organisms) is the presence of immunity proteins.
Immunity protein 52 (Imm52)
Type: Domain

This entry represents a domain found in bacteria, including the type VI secretion system (T6SS) immunity protein TsiT from Pseudomonas aeruginosa (

), which belongs to the Imm52 family. This protein can suppress the virulence of TseT . TsiT adopts a β-sandwich fold with nine α-helices and an eight-stranded antiparallel central β-sheet. It has a large electro-negative pocket with hydrophobic surroundings that play a role in the interaction with TseT . Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Tox-REase-5 family .
Protein of unknown function DUF4662 (DUF4662)
Type: Family

This entry represents a group of eukaryotic proteins that are uncharacterised.
NAD-glutamate dehydrogenase, catalytic domain (NAD-GDH_cat)
Type: Domain

This entry represents the catalytic domain of several proteins which are closely related to NAD-glutamate dehydrogenase found in Streptomyces clavuligerus. Glutamate dehydrogenases (GDHs) are a broadly distributed group of enzymes that catalyse the reversible oxidative deamination of glutamate to ketoglutarate and ammonia . The structure of GDH from Mycobacterium smegmatis revealed that it has long N- and C-terminal segments flanking the catalytic core which provide dimer-like interactions between pairs of monomers . The N-terminal segment is flexible and contains ACT-like and PAS-type domains that may play a role as metabolic sensors for allosteric regulation .

Glutamate dehydrogenases (GDHs) are a broadly distributed group of enzymes that catalyse the reversible oxidative deamination of glutamate to ketoglutarate and ammonia .
PhnB-like (PhnB-like)
Type: Domain

The Escherichia coli phnB gene is found next to an operon of fourteen genes (phnC-to-phnP) related to the cleavage of carbon-phosphorus (C-P) bonds in unactivated alkylphosphonates, supporting bacterial growth on alkylphosphonates as the sole phosphorus source. It was originally considered part of that operon. PhnB appears to play no direct catalytic role in the usage of alkylphosphonate . PA2721, an uncharacterised protein from P. aeruginosa, also belongs to this family .
TSP type-3 repeat (TSP_type-3_rpt)
Type: Homologous_superfamily

This entry represents the calcium-binding type 3 (T3) repeats found in extracellular calcium-binding multifunctional proteins, thrombospondins (TSPs). The T3 repeats lack secondary structure and are organised around a core of calcium ions; two DxDxDGxxDxxD motifs per repeat each encapsulate two calcium ions in a novel arrangement .
Diol dehydratase-reactivating factor, alpha subunit, swiveling domain superfamily (DDRA_swiveling_dom_sf)
Type: Homologous_superfamily

This superfamily represents the swivelling β/β/α domain found in diol dehydratase-reactivating factor alpha subunit (DDRA).

DDRA is the alpha subunit of the diol dehydratase-reactivating factor (DDR) or DD reactivase. DDR reactivates the inactivated diol dehydratase holoenzyme in the presence of ATP and magnesium by mediating the exchange of the tightly bound damaged cofactor for free intact coenzyme . The reactivation is mediated by a complex of two proteins: a large subunit (DdrA/PduG) and a small subunit (DdrB/PduH,

) .
CheC-like superfamily (CheC-like_sf)
Type: Homologous_superfamily

This superfamily represents a domain found in the CheC-like proteins. In bacteria, CheC is involved in restoration of prestimulus levels of the chemotactic response regulator, CheY-P . Proteins contain this domain include flagellar motor switch protein FliM/FliY and CheX, both CheY-P phosphatases .
Chorismate pyruvate-lyase/UbiC transcription regulator-associated domain superfamily (Chorismate_lyase_/UTRA_dom_sf)
Type: Homologous_superfamily

This superfamily represents a domain found in chorismate pyruvate-lyases, which catalyses the first step in ubiquinone synthesis, the removal of pyruvate from chorismate, to yield 4-hydroxybenzoate in Escherichia coli and other Gram-negative bacteria . The yeast Saccharomyces cerevisiae can synthesize ubiquinone from either chorismate or tyrosine , however this enzyme is found only in bacteria. Its activity does not require metal cofactors .

GntR/HutC-type transcriptional regulators also contain this domain, such as FrlR , TreR (trehalose operon transcriptional repressor) and PhnF .
HPr(Ser) kinase/phosphorylase-like, N-terminal domain superfamily (Ser_kin/Pase_Hpr-like_N_sf)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain of HprK (HPr kinase/phosphorylase) and domains similar to it, such as the DRTGG domain.

HprK is the sensor in a multicomponent phosphorelay system in control of carbon catabolic repression in bacteria . It is unusual in that it recognises the tertiary structure of its target and is a member of a novel family unrelated to any previously described protein phosphorylating enzymes . X-ray analysis of the full-length crystalline enzyme from Staphylococcus xylosus at a resolution of 1.95 A shows the enzyme to consist of two clearly separated domains that are assembled in a hexameric structure resembling a three-bladed propeller. The blades are formed by two N-terminal domains each, and the compact central hub assembles the C-terminal kinase domains .
PA2201-like, C-terminal (PA2201-like_C)
Type: Homologous_superfamily

This superfamily represents a seven-helical bundle domain that can be found in the C-terminal of the uncharacterised protein PA2201 from Pseudomonas aeruginosa (

).

PoNe immunity proteins (PoNi) are members of this superfamily. PoNi antagonise the DNAse toxin PoNe (Polymorphic Nuclease effector) . PoNi proteins may directly interact with PoNe .
Bacillus phage protein-like (Bacillus_phage_prot-like)
Type: Homologous_superfamily

This entry represents bacillus phage protein BC1872 and similar proteins from bacteria. They form a three-layer β/α/β sandwich . Their function is still not clear.
AF2331-like domain (AF2331-like_dom)
Type: Domain

AF2331-like protein is a 11kDa orphan protein from Archaeoglobus fulgidus. The structure consists of an α + β fold formed by an unusual homodimer, where the two core β-sheets are interdigitated, containing strands alternating from both subunits. AF2331 contains multiple negatively charged surface clusters and is located on the same operon as the basic protein AF2330. It is suggested that AF2331 and AF2330 may form a charge-stabilised complex in vivo, though the role of the negatively charged surface clusters is not clear .
F-type ATP synthase subunit B-like, membrane domain superfamily (ATP_synth_B-like_membr_sf)
Type: Homologous_superfamily

The b subunit of the E. coli F-type ATP synthase is present as a dimer and links the peripheral F(1) subunits to the membrane-integral F(0) portion. The dimerisation domain of the b subunit consists of an α-helical coiled-coil structure. In the dimer the two helices form a coiled coil with a right-handed superhelical twist. Analysis of b sequences from other prokaryotes indicates conservation of an undecad repeat in this domain . This superfamily represents a membrane domain that covers most of the dimerisation domain of the b subunit of the E. coli F-type ATP synthase.
Hemolytic lectin CEL-III, C-terminal domain superfamily (CEL-III_C_sf)
Type: Homologous_superfamily

Hemolytic lectin CEL-III is a Ca(2+)-dependent and galactose-specific lectin from the sea cucumber (Cucumaria echinata). CEL-III exhibits hemolytic and hemagglutinating activities . CEL-III contains two N-terminal carbohydrate-binding domains (domains 1 and 2) and a C-terminal domain (domain 3) . This superfamily represents the C-terminal domain, which contains hydrophobic segments and may be involved in the oligomerisation in the target cell membrane .
Ribosome maturation factor RimP, N-terminal (RimP_N)
Type: Domain

This entry represents the N-terminal domain of the ribosome maturation factor RimP (also known as yhbC), which facilitates maturation of the 30S ribosomal subunit . The N-terminal domain contains two α-helices and a three-stranded β-sheet .
GK1464-like (GK1464-like)
Type: Homologous_superfamily

This entry represents a group of uncharacterised bacterial proteins, including GK1464 from Geobacillus kaustophilus.
D-lysine 5,6-aminomutase beta subunit KamE, N-terminal (KamE_N)
Type: Domain

D-lysine 5,6-aminomutase beta subunit KamE catalyses the 1,2-migration of the D-lysine epsilon amino group to the δ-carbon with concomitant reverse migration of a hydrogen atom to produce 2,5-diaminohexanoic acid .
Hedgehog/Intein (Hint) domain (Hedgehog/Intein_dom)
Type: Domain

This entry represents a domain found in the pretoxin HINT domain protein and the C-terminal of protein hedgehog.

Hedgehog proteins are a family of secreted signal molecules required for embryonic cell differentiation. They are synthesised as inactive precursors with an N-terminal signalling domain linked to a C-terminal autoprocessing domain. The three-dimensional structure of the autoprocessing domain shows similarity with the β-strand core of intein splicing domains. It has hence been termed the Hedgehog/Intein (Hint) domain .
RecG, N-terminal antiparallel four helix bundle (RecG_N)
Type: Domain

ATP-dependent DNA helicase RecG is involved in the processing of stalled replication forks. It acts by reversing the fork past the damage to create a four-way junction that allows template switching and lesion bypass . RecG comprises three structural domains: N-terminal domain 1 (residues 1-350) and C-terminal domain 2 (residues 351-549) and domain3 (residues 550-780). This entry represents an antiparallel four helix bundle motif of the domain 1 .
Integrin alpha, N-terminal (Integrin_alpha_N)
Type: Homologous_superfamily

This superfamily represents a region containing the β-propeller folds found at the N terminus of integrin alpha.

Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton and activate many intracellular signalling pathways . The integrin receptors are composed of alpha and beta subunit heterodimers. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Within the N-terminal domain of alpha subunits, seven sequence repeats, each of approximately 60 amino acids, have been found .
Glycoside hydrolase families 57/38, central domain superfamily (Glyco_hydro_57/38_cen_sf)
Type: Homologous_superfamily

This superfamily represents a domain found in members of the glycosyl hydrolases families 57 and 38 . This central domain adopts a structure consisting of three α helices and forms an immunoglobulin/albumin-binding domain-like fold. This domain can also be found in the C-terminal of the Alpha-amylase AmyC protein.
Ganglioside GM2 activator (GM2-AP)
Type: Family

Ganglioside GM2 activator (GM2-AP) is a is a lysosomal lipid transfer protein that is essential for the hydrolytic conversion of ganglioside GM2 to GM3 by beta-hexosaminidase A . The crystal structure of apo-GM2-AP consists of a novel β-cup fold with a spacious hydrophobic interior .
PA2201-like, N-terminal (PA2201-like_N)
Type: Homologous_superfamily

This superfamily represents a four α-helix domain such as that found at the N terminus of Pseudomonas aeruginosa uncharacterised protein PA2201 (

).
Ribosome maturation factor RimP, C-terminal (RimP_C)
Type: Domain

The RimP protein (also known as YlxS in Bacillus subtilis) facilitates maturation of the 30S ribosomal subunit, and is required for the efficient production of translationally competent ribosomes .

This entry represents the C-terminal SH3-type barrel domain of RimP.
Haemocyanin, beta-sandwich domain (Beta-sandwich_Haemocyanin)
Type: Domain

This antiparallel β-sandwich domain occurs in the C-terminal of mollusc haemocyanins. Hemocyanins are copper-containing oxygen carriers occurring freely dissolved in the hemolymph of many mollusks and arthropods. Each mollusc haemocyanin contains several globular oxygen binding functional units. Each unit consists of an α-helical copper binding domain (

) and an antiparallel β-sandwich domain .
Cyclophilin-like domain superfamily (Cyclophilin-like_dom_sf)
Type: Homologous_superfamily

This superfamily represents a β-barrel domain that constitutes the core of cyclophilin-type peptidyl-prolyl cis-trans isomerases (

) and can also be found in the C-terminal of some bacterial uncharacterised proteins, such as PH0987 from Pyrococcus horikoshii (

) and

from Bacillus cereus.
Inosine triphosphate pyrophosphatase-like (ITPase-like_fam)
Type: Homologous_superfamily

This entry represents the inosine triphosphate pyrophosphatase (ITPase)-like proteins. Members in this family include NTPases, such as Ham1-like protein (non-canonical purine NTP pyrophosphatase) and non-canonical purine NTP phosphatase (YjjX-like), Maf-like proteins and PRRC1.

Non-canonical purine NTP phosphatases are prokaryotic phosphatases that hydrolyse non-canonical purine nucleotides such as XTP and ITP to their respective diphosphate derivatives .

Ham1 is a pyrophosphatase that hydrolyses the non-canonical purine nucleotides inosine triphosphate (ITP), deoxyinosine triphosphate (dITP) as well as 2'-deoxy-N-6-hydroxylaminopurine triphosphate (dHAPTP) and 5-bromodeoxyuridine 5'-triphosphate (BrdUTP) to their respective monophosphate derivatives .

Maf proteins exhibit nucleotide pyrophosphatase activity against canonical and modified nucleotides . Proline-rich and coiled-coil-containing protein 1 (PRRC1) is a Golgi-associated protein of unknown function .
Phospholipase C/D (PLPC/GPLD1)
Type: Domain

This domain is found in bacterial zinc-dependent phospholipase C and in eukaryotic phosphatidylinositol-glycan-specific phospholipase D.

Bacterial phospholipase C is a zinc-dependent enzyme, binding 3 zinc ions per molecule . This enzyme catalyses the conversion of phosphatidylcholine and water to 1,2-diacylglycerol and choline phosphate. Phosphatidylinositol-glycan-specific phospholipase D is an extracellular amphiphilic glycoprotein . It hydrolyses the inositol phosphate linkage in proteins anchored by phosphatidylinositol glycans, releasing these proteins from the membrane.
CENP-S/Mhf1 (CENP-S/Mhf1)
Type: Family

This entry includes animal centromere protein S (CENP-S) and its yeast homologue, Mhf1. CENP-S/Mhf1 is a component of the FANCM-MHF complex, an essential DNA-remodeling complex that protects replication forks in response to DNA damage . FANCM-MHF promotes gene conversion at blocked replication forks, probably by reversal of the stalled fork .

CENP-S is a dual function protein. It aids DNA repair/recombination and localises to centromeres to promote chromosome segregation . It is a kinetochore component that forms complexes with CENP-X to form a stable CENP-T-W-S-X heterotetramer .
Ribosomal eL28/Mak16 (Ribosomal_eL28/Mak16)
Type: Domain

Ribosomal protein eL28 forms part of the 60S ribosomal subunit . This entry is found in eukaryotes. In rat there are 9 or 10 copies of the eL28 gene. The eL28 protein contains a possible internal duplication of 9 residues .

In budding yeast, Mak16 forms part of the 66S pre-ribosomal particles and functions as a transacting actor involved in rRNA processing .

This entry represents a ribosomal L28e domain that also matches the N-terminal region of Mak16.
LIM-domain binding protein/SEUSS (LIM-bd/SEUSS)
Type: Family

This entry includes the LIM-domain binding proteins and similar proteins, such as protein Chip from Drosophila, SEUSS from Arabidopsis and Adn1 from fission yeasts.
ADF-H/Gelsolin-like domain superfamily (ADF-H/Gelsolin-like_dom_sf)
Type: Homologous_superfamily

This superfamily represents an ~150-amino acid ADF-H (actin-depolymerising factor homology) domain found in three phylogenetically distinct classes of eukaryotic actin-binding proteins . This domain shares structural similarity with another set of actin binding proteins, villin and gelsolin, and the C-terminal of the Sec23/Sec24 proteins. It consists of a mixed β-sheet structure.