SII-SWORD/CoKE huggingface dataset:
2-5OAS/ClassI-CCAase, nucleotidyltransferase domain (NT_2-5OAS_ClassI-CCAase)
Type: Domain

Proteins containing this domain include human OAS1, -2, -3, and OASL. CCA-adding enzymes add the sequence [cytidine(C)-cytidine-adenosine (A)], one nucleotide at a time, onto the 3' end of tRNA, in a template-independent reaction. This class I group includes the archaeal Sulfolobus shibatae and Archeoglobus fulgidus CCA-adding enzymes. It belongs to the Pol beta-like NT superfamily. In the majority of enzymes in this superfamily, two carboxylates, Dx[D/E], together with a third more distal carboxylate, coordinate two divalent metal cations involved in a two-metal ion mechanism of nucleotide addition. These carboxylate residues are conserved in this family .

In vertebrates, 2-5OASs (2'-5'-oligoadenylate synthetases) are induced by interferon during the innate immune response to protect against RNA virus infections. In the presence of an RNA activator, 2-5OASs catalyze the oligomerization of ATP into 2-5A. 2-5A activates endoribonuclease L, which leads to degradation of the viral RNA. 2-5OASs are also implicated in cell growth control, differentiation, and apoptosis .

Three distinct classes of 2-5A synthetases have been described that correspond to proteins of 40-46 Kd, 69-71 Kd, and 100 Kd. The 40 and 46 Kd forms are produced by alternative splicing of the same gene. The 69 and 71 Kd forms are also produced by alternative splicing of a gene and consist of two adjacent homologous domains whose sequences are highly similar to that of the 40/46 Kd forms. The sequence of the 100 Kd form is not yet known.
2-5-oligoadenylate synthetase, C-terminal conserved site (2-5OAS_C_CS)
Type: Conserved_site

In vertebrates, 2-5OASs (2'-5'-oligoadenylate synthetases) are induced by interferon during the innate immune response to protect against RNA virus infections. In the presence of an RNA activator, 2-5OASs catalyze the oligomerization of ATP into 2-5A. 2-5A activates endoribonuclease L, which leads to degradation of the viral RNA. 2-5OASs are also implicated in cell growth control, differentiation, and apoptosis .

Three distinct classes of 2-5A synthetases have been described that correspond to proteins of 40-46 Kd, 69-71 Kd, and 100 Kd. The 40 and 46 Kd forms are produced by alternative splicing of the same gene. The 69 and 71 Kd forms are also produced by alternative splicing of a gene and consist of two adjacent homologous domains whose sequences are highly similar to that of the 40/46 Kd forms. The sequence of the 100 Kd form is not yet known.

This domain corresponds to a highly conserved region located in the C-terminal part of 2-5-oligoadenylate synthetase.
Recombinase, conserved site (Recombinase_CS)
Type: Conserved_site

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

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

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

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

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

The resolvase family is currently known to include the following proteins:

DNA invertase from Salmonella typhimurium (gene hin). Hin can invert a 900 bp DNA fragment adjacent to a gene for one of the flagellar antigens.

DNA invertase from Escherichia coli (gene pin).

DNA invertase from Bacteriophage Mu (gene gin), P1 and P7 (gene cin).

Resolvases from transposons Tn3, Tn21, Tn501, Tn552, Tn917, Tn1546, Tn1721, Tn2501 and Tn1000 (known as gamma-delta resolvase).

Resolvase from Clostridium perfringens plasmid pIP404.

Resolvase from E. coli plasmid R46.

Resolvase from E. coli plasmid RP4 (gene parA).

A putative recombinase from Bacillus subtilis (gene cisA) which plays an important role in sporulation by catalyzing the recombination of genes spoIIIC and spoIVCB to form polymerase sigma-K factor.

Uvp1, a protein from E. coli plasmid pR which cooperates with the mucAB genes in the DNA repair process and could be a resolvase .

Generally, proteins from the resolvase family have 180 to 200 amino-acid residues, excepting cisA which is much larger (500 residues).
Resolvase, N-terminal catalytic domain (Resolv_N)
Type: Domain

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

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

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

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

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

).
Resolvase, HTH domain (Resolvase_HTH_dom)
Type: Domain

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

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

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

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

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

, and a C-terminal helix-turn-helix DNA-binding domain.
Heavy metal-associated domain, HMA (HMA_dom)
Type: Domain

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

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

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

Structure solution of the fourth HMA domain of the Menke's copper transporting ATPase shows a well-defined structure comprising a four-stranded antiparallel β-sheet and two α-helices packed in an α-β sandwich fold . This fold is common to other domains and is classified as "ferredoxin-like".
Heavy metal-associated domain, copper ion-binding (HMA_Cu_ion-bd)
Type: Domain

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

These proteins provide an important focus for research, some being involved in bacterial resistance to toxic metals, such as lead and cadmium, while others are involved in inherited human syndromes, such as Wilson's and Menke's diseases .
Staphylococcal/Streptococcal toxin, beta-grasp domain (Toxin_b-grasp_Staph/Strep)
Type: Domain

Staphylococcal enterotoxins and streptococcal pyrogenic exotoxins constitute a family of biologically and structurally related toxins produced by Staphylococcus aureus and Streptococcus pyogenes . These toxins share the ability to bind to the major histocompatibility complex proteins of their hosts. A more distant relative of the family is the S. aureus toxic shock syndrome toxin, which shares only a low level of sequence similarity with this group.

All of these toxins share a similar two-domain fold (N and C-terminal domains) with a long α-helix in the middle of the molecule, a characteristic β-barrel known as the "oligosaccharide/oligonucleotide fold" at the N-terminal domain and a β-grasp motif at the C-terminal domain. Each superantigen possesses slightly different binding mode(s) when it interacts with MHC class II molecules or the T-cell receptor .

The β-grasp domain has some structural similarities to the β-grasp motif present in immunoglobulin-binding domains, ubiquitin, 2Fe-2 S ferredoxin and translation initiation factor 3 as identified by the SCOP database.
Metalloenzyme (Metalloenzyme)
Type: Domain

This domain unites alkaline phosphatase, N-acetylgalactosamine-4-sulphatase, and cerebroside sulphatase, enzymes with known three-dimensional structures, with phosphopentomutase, 2,3-bisphosphoglycerate-independent phosphoglycerate mutase, phosphoglycerol transferase, phosphonate monoesterase, streptomycin-6-phosphate phosphatase, alkaline phosphodiesterase/nucleotide pyrophosphatase PC-1, and several closely related sulphatases. This domain is also related to alkaline phosphatase

. The most conserved residues are probably involved in metal binding and catalysis.
Staphylococcal enterotoxin/Streptococcal pyrogenic exotoxin, conserved site (Staph/Strept_toxin_CS)
Type: Conserved_site

Staphylococcal enterotoxins and streptococcal pyrogenic exotoxins constitute a family of biologically and structurally related toxins produced by Staphylococcus aureus and Streptococcus pyogenes . These toxins share the ability to bind to the major histocompatibility complex proteins of their hosts. A more distant relative of the family is the S. aureus toxic shock syndrome toxin (TSST-1), which shares only a low level of sequence similarity with this group.

This family is identified by a well conserved region of enterotoxins and pyrogenic exotoxins, but which does not pick up TSST-1.
Periplasmic solute binding protein, ZnuA-like (ZnuA-like)
Type: Family

Members of this family constitute the solute-binding protein component of cluster-9 ABC transporters. This family includes periplasmic solute binding protein TroA from Treponema pallidum, which binds Zn2+ and Mn2+ . In Streptococcus suis, TroA is required for manganese acquisition . Related proteins are found in both Gram-positive and Gram-negative bacteria, including manganese-binding lipoprotein MntA and high-affinity zinc uptake system protein ZnuA .

ZnuA is part of the bacterial zinc-uptake complex ZnuABC. ZinT acts as a Zn2+-buffering protein that delivers Zn2+ to ZnuA, a high-affinity zinc-uptake protein. In Gram-negative bacteria the ZnuABC transporter system ensures an adequate import of zinc in Zn2+-poor environments, such as those encountered by pathogens within the infected host .
Adhesion lipoprotein PsaA-like (Lipoprotein_PsaA-like)
Type: Family

The Streptococcus pneumoniae psaA gene encodes a protein with significant similarity to previously-reported Streptococcal proteins, SsaB (80% similarity) and FimA (92.3% similarity), from Streptococcus sanguis and Streptococcus parasanguis . These homologues are associated with bacterial adhesion . PsaA is part of the ATP-binding cassette (ABC) transport system PsaABC involved in manganese import . It binds manganese with high affinity and specificity and delivers it to the membrane permease for translocation into the cytoplasm . PsaA also acts as an adhesin which is involved on adherence to extracellular matrix being an important factor in pathogenesis and infection .

The SsaB protein has a putative hydrophobic 19-amino-acid signal sequence yielding a 32,620-Mr secreted protein . SsaB is hydrophilic and appears not to have a hydrophobic membrane anchor in its C-terminal region. A high degree of similarity exists between S. sanguis ssaB and type 1 fimbrial genes . Comparison of the gene products reveals close similarity of the two proteins. It is thought that ssaB adhesion may play a role in oral colonisation by binding either to a receptor on saliva or to a receptor on Actinomyces.

This family includes adhesins and related periplasmic binding proteins.
Adhesin B (AdhesinB)
Type: Family

The Streptococcus pneumoniae psaA gene encodes a protein with significant similarity to previously-reported Streptococcal proteins, SsaB (80% similarity) and FimA (92.3% similarity), from Streptococcus sanguis and Streptococcus parasanguis . These homologues are associated with bacterial adhesion, and PsaA may play a similar role .

The SsaB protein has a putative hydrophobic 19-amino-acid signal sequence yielding a 32,620-Mr secreted protein . SsaB is hydrophilic and appears not to have a hydrophobic membrane anchor in its C-terminal region. A high degree of similarity exists between S. sanguis ssaB and type 1 fimbrial genes . Comparison of the gene products reveals close similarity of the two proteins. It is thought that ssaB adhesion may play a role in oral colonisation by binding either to a receptor on saliva or to a receptor on Actinomyces.

This sub-family is described by from conserved regions spanning the full alignment length, focusing on those sections that characterise the adhesin B precursors but distinguish them from the rest of the adhesin family.
Aspartate/ornithine carbamoyltransferase (Asp/Orn_carbamoylTrfase)
Type: Family

This family contains two related enzymes:

Aspartate carbamoyltransferase (

) (ATCase) catalyses the conversion of aspartate and carbamoyl phosphate to carbamoylaspartate, the second step in the
de novo
biosynthesis of pyrimidine nucleotides . In prokaryotes ATCase consists of two subunits: a catalytic chain (gene pyrB) and a regulatory chain (gene pyrI), while in eukaryotes it is a domain in a multi-functional enzyme (called URA2 in yeast, rudimentary in Drosophila, and CAD in mammals ) that also catalyses other steps of the biosynthesis of pyrimidines .

Ornithine carbamoyltransferase (

) (OTCase) catalyses the conversion of ornithine and carbamoyl phosphate to citrulline. In mammals, this enzyme participates in the urea cycle and is located in the mitochondrial matrix. In prokaryotes and eukaryotic microorganisms it is involved in the biosynthesis of arginine. In some bacterial species it is also involved in the degradation of arginine (the arginine deaminase pathway).

It has been shown that these two enzymes are evolutionary related. The predicted secondary structure of both enzymes are similar and there are some regions of sequence similarities. One of these regions includes three residues which have been shown, by crystallographic studies , to be implicated in binding the phosphoryl group of carbamoyl phosphate.
Aspartate/ornithine carbamoyltransferase, Asp/Orn-binding domain (Asp_carbamoyltransf_Asp/Orn-bd)
Type: Domain

This family contains two related enzymes:

Aspartate carbamoyltransferase (

) (ATCase) catalyzes the conversion of aspartate and carbamoyl phosphate to carbamoylaspartate, the second step in the
de novo
biosynthesis of pyrimidine nucleotides . In prokaryotes ATCase consists of two subunits: a catalytic chain (gene pyrB) and a regulatory chain (gene pyrI), while in eukaryotes it is a domain in a multi- functional enzyme (called URA2 in yeast, rudimentary in Drosophila, and CAD in mammals ) that also catalyzes other steps of the biosynthesis of pyrimidines.

Ornithine carbamoyltransferase (

) (OTCase) catalyzes the conversion of ornithine and carbamoyl phosphate to citrulline. In mammals this enzyme participates in the urea cycle and is located in the mitochondrial matrix. In prokaryotes and eukaryotic microorganisms it is involved in the biosynthesis of arginine. In some bacterial species it is also involved in the degradation of arginine (the arginine deaminase pathway).

It has been shown that these two enzymes are evolutionary related. The predicted secondary structure of both enzymes are similar and there are some regions of sequence similarities. One of these regions includes three residues which have been shown, by crystallographic studies , to be implicated in binding the phosphoryl group of carbamoyl phosphate and is described by

. The carboxyl-terminal, aspartate/ornithine-binding domain is connected to the amino-terminal domain by two α-helices, which comprise a hinge between domains .
Aspartate/ornithine carbamoyltransferase, carbamoyl-P binding (Asp/Orn_carbamoyltranf_P-bd)
Type: Domain

This entry contains two related enzymes:

Aspartate carbamoyltransferase (

) (ATCase) catalyzes the conversion of aspartate and carbamoyl phosphate to carbamoylaspartate, the second step in the
de novo
biosynthesis of pyrimidine nucleotides . In prokaryotes ATCase consists of two subunits: a catalytic chain (gene pyrB) and a regulatory chain (gene pyrI), while in eukaryotes it is a domain in a multi- functional enzyme (called URA2 in yeast, rudimentary in Drosophila, and CAD in mammals ) that also catalyzes other steps of the biosynthesis of pyrimidines.

Ornithine carbamoyltransferase (

) (OTCase) catalyzes the conversion of ornithine and carbamoyl phosphate to citrulline. In mammals this enzyme participates in the urea cycle and is located in the mitochondrial matrix. In prokaryotes and eukaryotic microorganisms it is involved in the biosynthesis of arginine. In some bacterial species it is also involved in the degradation of arginine (the arginine deaminase pathway).

It has been shown that these two enzymes are evolutionary related. The predicted secondary structure of both enzymes are similar and there are some regions of sequence similarities. One of these regions includes three residues which have been shown, by crystallographic studies , to be implicated in binding the phosphoryl group of carbamoyl phosphate and may also play a role in trimerization of the molecules . The carboxyl-terminal, aspartate/ornithine-binding domain is is described by

.
DNA-directed DNA polymerase, family B, exonuclease domain (DNA-dir_DNA_pol_B_exonuc)
Type: Domain

DNA is the biological information that instructs cells how to exist in an ordered fashion: accurate replication is thus one of the most important events in the life cycle of a cell. This function is performed by DNA- directed DNA-polymerases

) by adding nucleotide triphosphate (dNTP) residues to the 5'-end of the growing chain of DNA, using a complementary DNA chain as a template. Small RNA molecules are generally used as primers for chain elongation, although terminal proteins may also be used for the de novo synthesis of a DNA chain. Even though there are 2 different methods of priming, these are mediated by 2 very similar polymerases classes, A and B, with similar methods of chain elongation. A number of DNA polymerases have been grouped under the designation of DNA polymerase family B. Six regions of similarity (numbered from I to VI) are found in all or a subset of the B family polymerases. The most conserved region (I) includes a conserved tetrapeptide with two aspartate residues. Its function is not yet known. However, it has been suggested that it may be involved in binding a magnesium ion. All sequences in the B family contain a characteristic DTDS motif, and possess many functional domains, including a 5'-3' elongation domain, a 3'-5' exonuclease domain , a DNA binding domain, and binding domains for both dNTP's and pyrophosphate .
DNA-directed DNA polymerase, family B, multifunctional domain (DNA-dir_DNA_pol_B_multi_dom)
Type: Domain

DNA is the biological information that instructs cells how to exist in an ordered fashion: accurate replication is thus one of the most important events in the life cycle of a cell. This function is performed by DNA- directed DNA-polymerases

) by adding nucleotide triphosphate (dNTP) residues to the 5'-end of the growing chain of DNA, using a complementary DNA chain as a template. Small RNA molecules are generally used as primers for chain elongation, although terminal proteins may also be used for the de novo synthesis of a DNA chain. Even though there are 2 different methods of priming, these are mediated by 2 very similar polymerases classes, A and B, with similar methods of chain elongation.
A number of DNA polymerases have been grouped under the designation of DNA polymerase family B. Six regions of similarity (numbered from I to VI) are found in all or a subset of the B family polymerases. The most conserved region (I) includes a conserved tetrapeptide with two aspartate residues. Its function is not yet known, however, it has been suggested that it may be involved in binding a magnesium ion. All sequences in the B family contain a characteristic DTDS motif, and possess many functional domains, including a 5'-3' elongation domain, a 3'-5' exonuclease domain , a DNA binding domain, and binding domains for both dNTP's and pyrophosphate .

This domain of DNA polymerase B appears to consist of more than one activities, possibly including elongation, DNA-binding and dNTP binding .
Type III secretion system substrate exporter (T3SS_substrate_exporter)
Type: Family

Salmonella, and related proteobacteria, secrete large amounts of proteins into the culture media. The major secreted proteins are either flagellar proteins or virulence factors , secreted through the flagellar or virulence export structures respectively. Both secretion systems penetrate the inner and outer membranes and their components bear substantial sequence similarity. Both the flagellar and needle like pilus look fairly similar to each other .

The type III secretion system is of great interest, as it is used to transport virulence factors from the pathogen directly into the host cell and is only triggered when the bacterium comes into close contact with the host.
Flagellar biosynthetic protein FlhB (FlhB)
Type: Family

FlhB and its functionally equivalent orthologues, from among a larger superfamily of proteins involved in type III protein export systems, are involved in flagellar protein export . Proteins in this entry play roles specifically related to flagellar structures .