SII-SWORD/CoKE huggingface dataset:
Guanine nucleotide exchange factor SopE, N-terminal domain (SopE_N_dom)
Type: Domain

The type III secretion system of Gram-negative bacteria 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. Effector proteins secreted by the type III system do not possess a secretion signal, and are considered unique because of this. Salmonella spp. secrete an effector protein called SopE that is responsible for stimulating the reorganisation of the host cell actin cytoskeleton, and ruffling of the cellular membrane . It acts as a guanyl-nucleotide-exchange factor on Rho-GTPase proteins such as Cdc42 and Rac. As it is imperative for the bacterium to revert the cell back to its "normal" state as quickly as possible, another tyrosine phosphatase effector called SptP reverses the actions brought about by SopE .

Recently, it has been found that SopE and its protein homologue SopE2 can activate different sets of Rho-GTPases in the host cell . Far from being a redundant set of two similar type III effectors, they both act in unison to specifically activate different Rho-GTPase signalling cascades in the host cell during infection.

This entry represents the N-terminal domain of SopE and SopE2. The function of this domain is unknown.
Guanine nucleotide exchange factor SopE, GEF domain (SopE_GEF_dom)
Type: Domain

This entry represents the guanine nucleotide exchange factor domain of SopE. This domain has an α-helical structure consisting of two three-helix bundles arranged in a lamdba shape .

The type III secretion system of Gram-negative bacteria 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. Effector proteins secreted by the type III system do not possess a secretion signal, and are considered unique because of this. Salmonella spp. secrete an effector protein called SopE that is responsible for stimulating the reorganisation of the host cell actin cytoskeleton, and ruffling of the cellular membrane . It acts as a guanyl-nucleotide-exchange factor on Rho-GTPase proteins such as Cdc42 and Rac. As it is imperative for the bacterium to revert the cell back to its "normal" state as quickly as possible, another tyrosine phosphatase effector called SptP reverses the actions brought about by SopE .
Translation initiation factor 3, subunit 12, N-terminal, eukaryotic (Transl_init_fac_sub12_N_euk)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain found in several eukaryotic translation initiation factor 3 subunit 12 (eIF-3 p25; also known as subunit K) proteins. Eukaryotic initiation factor 3 (eIF3) is a multi-subunit complex that is required for binding of mRNA to 40S ribosomal subunits, stabilisation of ternary complex binding to 40S subunits, and dissociation of 40S and 60S subunits .
Armadillo-type fold (ARM-type_fold)
Type: Homologous_superfamily

This entry represents a structural domain with an armadillo (ARM)-like fold, consisting of a multi-helical fold comprised of two curved layers of α-helices arranged in a regular right-handed superhelix, where the repeats that make up this structure are arranged about a common axis . These superhelical structures present an extensive solvent-accessible surface that is well suited to binding large substrates such as proteins and nucleic acids.

The sequence similarity among these different repeats or domains is low, however they exhibit considerable structural similarity. Furthermore, the number of repeats present in the superhelical structure can vary between orthologues, indicating that rapid loss/gain of repeats has occurred frequently in evolution. A common phylogenetic origin has been proposed for the armadillo and HEAT repeats .
Clathrin heavy chain, N-terminal (Clathrin_H-chain_N)
Type: Homologous_superfamily

Proteins synthesized on the ribosome and processed in the endoplasmic reticulum are transported from the Golgi apparatus to the trans-Golgi network (TGN), and from there via small carrier vesicles to their final destination compartment. These vesicles have specific coat proteins (such as clathrin or coatomer) that are important for cargo selection and direction of transport . Clathrin coats contain both clathrin (acts as a scaffold) and adaptor complexes that link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. The two major types of clathrin adaptor complexes are the heterotetrameric adaptor protein (AP) complexes, and the monomeric GGA (Golgi-localising, Gamma-adaptin ear domain homology, ARF-binding proteins) adaptors .

Clathrin is a trimer composed of three heavy chains and three light chains, each monomer projecting outwards like a leg; this three-legged structure is known as a triskelion . The heavy chains form the legs, their N-terminal β-propeller regions extending outwards, while their C-terminal α-α-superhelical regions form the central hub of the triskelion. Peptide motifs can bind between the β-propeller blades. The light chains appear to have a regulatory role, and may help orient the assembly and disassembly of clathrin coats as they interact with hsc70 uncoating ATPase . Clathrin triskelia self-polymerise into a curved lattice by twisting individual legs together. The clathrin lattice forms around a vesicle as it buds from the TGN, plasma membrane or endosomes, acting to stabilise the vesicle and facilitate the budding process . The multiple blades created when the triskelia polymerise are involved in multiple protein interactions, enabling the recruitment of different cargo adaptors and membrane attachment proteins .

This entry represents a region covering the N-terminal β-propeller region of clathrin heavy chains that extends away from the hub of triskelia, and which is responsible for peptide binding , as well as the core motif for the α-helical zigzag linker region connecting the conserved N-terminal β-propeller region to the C-terminal α-α-superhelical region in clathrin heavy chains .
Inner layer core protein VP3, Reovirus (Inner_layer_core_VP3_Reovir)
Type: Homologous_superfamily

This entry represents the inner layer core protein VP3 from various Reoviruses, including Orbiviruses and Phytoreviruses, Reoviruses have dsRNA genomes of 10-12 linear segments . VP3 proteins and their homologues are found in the Orbiviruses Epizootic hemorrhagic disease virus and Bluetongue virus (BTV) , while the homologous VP2 protein is found in Broadhaven virus (BRD). VP3 proteins are also found in Phytoreviruses such as Rice dwarf virus (RDV).

The inner layer protein VP3 is part of the virus core and makes a 'subcore' shell made up of 120 copies of the 100K protein. VP3 particles can also bind RNA and are fundamental in the early stages of viral core formation. VP3 is a large protein without apparent domain divisions, but has a number of all-alpha regions and one all-beta region near the C-terminal .
Cobalamin adenosyltransferase-like (CblAdoTrfase-like)
Type: Domain

ATP:cob(I)alamin (or ATP:corrinoid) adenosyltransferases (

), catalyse the conversion of cobalamin (vitamin B12) into its coenzyme form, adenosylcobalamin (AdoCbl)or coenzyme B12 . AdoCbl contains an adenosyl moiety liganded to the cobalt ion of cobalamin via a covalent Co-C bond. AdoCbl is required as a cofactor for the activity of certain enzymes.

ATP:cob(I)alamin adenosyltransferases are classed into three groups: CobA-type , EutT-type and PduO-type . Each of the three enzyme types appears to be specialised for particular AdoCbl-dependent enzymes or for the de novo synthesis AdoCbl. PduO and EutT are distantly related, sharing short conserved motifs, while CobA is evolutionarily unrelated and is an example of convergent evolution.

This entry represents a structural domain consisting of 4-helical bundle with a left-handed twist and one cross-over loop that goes across to a different side of the 4-helical bundle; there is no internal metal-binding site. This domain is found in EutT- and PduO-type ATP:cob(I)alamin adenosyltransferases. PduO functions to convert cobalamin to AdoCbl for 1,2-propanediol degradation , while EutT produces AdoCbl for ethanolamine utilisation . This domain is also found in the hypothetical protein Ta1238 from the archaeon Thermoplasma acidophilum .
Tryptophan RNA-binding attenuator protein-like domain superfamily (Trp_RNA-bd_attenuator-like_dom)
Type: Homologous_superfamily

The tryptophan RNA-binding attenuation protein (TRAP) regulates expression of the tryptophan biosynthetic genes in Bacillus sp. by binding to the leader region of the nascent trp operon mRNA . The crystal structure of the Trp RNA-binding attenuation protein of Bacillus subtilis (mtrB,

) has been solved . TRAP forms an oligomeric ring consisting of 11 single-domain subunits, where each subunit adopts a double-stranded β-helix structure with the appearance of a β-sandwich of distinct architecture and jelly-roll fold. The 11 subunits are stabilised by 11 inter-subunit strands, forming a β-wheel with a large central hole. TRAP is activated by binding to tryptophan in clefts between adjacent β-strands, which induces conformational changes in the protein. Activated TRAP binds an mRNA target sequence consisting of 11 (G/U)AG repeats, separated by 2-3 spacer nucleotides. The spacer nucleotides do not make direct contact with the TRAP protein, but they do influence the conformation of the RNA, which might influence the specificity of TRAP .

This superfamily represents a domain with a TRAP-like double-stranded β-helix topology. This domain is found in TRAP proteins, as well as in the hypothetical protein SPyM3_0169 from Streptococcus pyogenes. SPyM3_0169 contains 9 domains per ring-like trimer, where each subunit contains three structural repeats.
Signal transduction response regulator, C-terminal effector (Sig_transdc_resp-reg_C-effctor)
Type: Homologous_superfamily

This entry represents a structural domain usually found at the C-terminal of bipartite response regulators. These proteins are known to bind to DNA and RNA polymerases, and their N-terminal receiver domain belongs to the CheY family. The C-terminal effector domain consists of a 3-helical bundle in an up-an-down arrangement with a right-handed twist. This domain occurs in:

PhoB-like proteins, which includes PhoB , OmpR , and DrrB ; these proteins contain a 4-stranded meander β-sheet in the N-terminal extension.

GerE-like proteins from the LuxR/UhpA family of proteins, which includes GerE , TraR (quorum-sensing) , NarL (nitrate/nitrite response regulator) , and RcsB transcriptional regulator ; these proteins contain an additional fourth helix in the C-terminal extension.

Spo0A proteins , which are elaborated with additional helices.

Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions . Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk . These pathways have been adapted to response to a wide variety of stimuli, including nutrients, cellular redox state, changes in osmolarity, quorum signals, antibiotics, and more . Two-component systems are comprised of a sensor histidine kinase (HK) and its cognate response regulator (RR) . The HK catalyses its own auto-phosphorylation followed by the transfer of the phosphoryl group to the receiver domain on RR; phosphorylation of the RR usually activates an attached output domain, which can then effect changes in cellular physiology, often by regulating gene expression. Some HK are bifunctional, catalysing both the phosphorylation and dephosphorylation of their cognate RR. The input stimuli can regulate either the kinase or phosphatase activity of the bifunctional HK.

A variant of the two-component system is the phospho-relay system. Here a hybrid HK auto-phosphorylates and then transfers the phosphoryl group to an internal receiver domain, rather than to a separate RR protein. The phosphoryl group is then shuttled to histidine phosphotransferase (HPT) and subsequently to a terminal RR, which can evoke the desired response .
DNA polymerase II large subunit DP2, N-terminal (PolC_DP2_N)
Type: Domain

This entry represents the N-terminal domain of the DNA polymerase II large subunit. This domain adopts an α/β structure.

DP2 is the large subunit of a two-subunit novel archaebacterial replicative DNA polymerase first characterised for Pyrococcus furiosus. The structure of DP2 appears to be organised as a ~950 residue component separated from a ~300 residue component by a ~150 residue intein. The other subunit, DP1, has sequence similarity to the eukaryotic DNA polymerase delta small subunit.
Acyl transferase/acyl hydrolase/lysophospholipase (Acyl_Trfase/lysoPLipase)
Type: Homologous_superfamily

This superfamily represents a structural domain with a 3-layer α/β/α topology. This domain can be found in acyl transferases such as bacterial malonyl-CoA ACP transacylase (FabD) and the homologous domain from eukaryotic fatty acid synthase . This domain is also found in lysophospholipases such as cytosolic phospholipase A2 (which has additional structural features) , and in patatin proteins, which are plant glycoproteins that act as non-specific lipid acyl hydrolases .
Malonyl-CoA ACP transacylase, ACP-binding (Malonyl_transacylase_ACP-bd)
Type: Homologous_superfamily

This entry represents a structural domain with an α/β sandwich topology with anti-parallel β-sheets: (β/α/β)2. This domain is believed to be the ACP (acyl carrier protein) binding region of the malonyl-CoA ACP transacylase enzyme (FabD) found in bacteria, or in the homologous domain from eukaryotic fatty acid synthase .
3-dehydroquinate synthase AroB (DHQ_synth_AroB)
Type: Family

The 3-dehydroquinate synthase (DHQS) domain can exist in isolation or as a domain in the pentafunctional AROM polypeptide (

) . 3-dehydroquinate synthase catalyses the formation of dehydroquinate (DHQ) and orthophosphate from 3-deoxy-D-arabino heptulosonic 7 phosphate . This reaction is part of the shikimate pathway which is involved in the biosynthesis of aromatic amino acids. DHQS consists of an N-terminal Rossmann-fold domain and a C-terminal α-helical domain. The active site is located in a cleft between the two domains.
Thiolase-like (Thiolase-like)
Type: Homologous_superfamily

This superfamily represents a structural domain with a thiolase-like 3-layer α/β/α topology. This domain usually occurs in two similar copies that are related by a pseudo-dyad, and which arose through duplication. The proteins in this entry can be split into two groups: those related to thiolase, and those related to chalcone synthase. The thiolase-like enzymes include:

Thiolase, where the topology of each domain is similar to the first domain of phosphoglucomutase

Beta-ketoacyl-ACP synthases types I (

), II (

) and III (

)

Actinorhodin polyketide beta-ketoacyl synthases 1 and 2

Fatty oxidation complex beta subunit (3-ketoacyl-CoA thiolase;

)

The chalcone synthase-like enzymes include:

Chalcone synthase (

)

Ketoacyl-ACP synthase III (FabH;

)

Polyketide synthases

3-hydroxy-3-methylglutaryl CoA synthase (

)

Dihydropinosylvin synthase
NAD(P)-binding domain (NAD(P)-bd_dom)
Type: Domain

This entry represents NAD- and NADP-binding domains with a core Rossmann-type fold, which consists of 3-layers α/β/α, where the six β-strands are parallel in the order 321456. Many different enzymes contain an NAD/NADP-binding domain, including:

C-terminal domain of alcohol dehydrogenases

Tyrosine-dependent oxidoreductases (also known as short-chain dehydrogenases)

N-terminal domain of glyceraldehyde-3-phosphate dehydrogenase

NAD-binding domain of formate/glycerate dehydrogenases

N-terminal domain of sirohaem synthase

N-terminal domain of lactate dehydrogenase

N-terminal domain of 6-phosphogluconate dehydrogenase (the β-sheet is extended to 8 strands)

C-terminal domain of amino acid dehydrogenases (an extra N-terminal helix displaces the C-terminal helix

NAD-binding domain of certain potassium channels

C-terminal domain of the transcriptional repressor Rex

Ornithine cyclodeaminase

CoA-binding N-terminal domain of the alpha chain of succinyl-CoA synthetase
CO dehydrogenase/acetyl-CoA synthase delta subunit, TIM barrel (Ac-CoA_synth_d_su_TIM-brl)
Type: Domain

This entry represents a conserved region predicted to form a TIM α/β barrel, and is found in the delta subunit of a number of CO dehydrogenase/acetyl-CoA synthase enzymes.
Tyrosine-protein kinase, non-receptor, TYK2, N-terminal (Tyr_kinase_non-rcpt_TYK2_N)
Type: Domain

Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process.
Protein kinases fall into three broad classes, characterised with respect to substrate specificity :

Serine/threonine-protein kinases

Tyrosine-protein kinases

Dual specificity protein kinases (e.g. MEK -phosphorylates both Thr and Tyr on target proteins)

Protein kinase function is evolutionarily conserved from Escherichia coli to human . Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved , leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases .

Tyrosine-protein kinases can transfer a phosphate group from ATP to a tyrosine residue in a protein. These enzymes can be divided into two main groups :

Receptor tyrosine kinases (RTK), which are transmembrane proteins involved in signal transduction; they play key roles in growth, differentiation, metabolism, adhesion, motility, death and oncogenesis . RTKs are composed of 3 domains: an extracellular domain (binds ligand), a transmembrane (TM) domain, and an intracellular catalytic domain (phosphorylates substrate). The TM domain plays an important role in the dimerisation process necessary for signal transduction .

Cytoplasmic/non-receptor tyrosine kinases, which act as regulatory proteins, playing key roles in cell differentiation, motility, proliferation, and survival. For example, the Src-family of protein-tyrosine kinases .

TYK2 was first identified by low-stringency hybridisation screening of a human lymphoid cDNA library with the catalytic domain of proto-oncogene c-fms . Mouse and puffer fish orthlogues have also been identified. In common with JAK1 and JAK2, and by contrast with JAK3, TYK2 appears to be ubiquitously expressed.

This entry represents the N-terminal region of TYK2.
M23ase, beta-sheet core domain (M23ase_b-sheet_dom)
Type: Domain

This entry represents the duplicated hybrid domain found in the M23 peptidase family in bacteria, which includes various peptidoglycan hydrolases with diverse specificities. Many members, such as Lysostaphin

, are Gly-Gly endopeptidases, while others like Protease LasA

have broader substrate specificity.

The duplicated hybrid motif is a structural motif that is found in certain glucose-permease-like enzymes, and consists of a half-barrel β-sheet of eight strands that is sandwiched with two 3-stranded β-sheets. Enzymes displaying this motif include domain IIa of the glucose-specific permease from bacteria (

) (

), which is part of the phosphoenolpyruvate:sugar phosphotransfer system (PTS), a bacterial and mycoplasma system responsible for the uptake of some sugars and their concomitant phosphorylation . This structural motif is also found in peptidoglycan hydrolase LytM in Staphylococcus aureus

, a member of peptidase family M23, although it contains an extra N-terminal, non-conserved β-sheet subdomain .

Peptidase M23 is a family of zinc-dependent metallopeptidases that play crucial roles in bacterial cell wall metabolism and peptidoglycan remodelling. These enzymes are characterised by a conserved β-sheet core

. The family includes both glycyl-glycine endopeptidases and enzymes with broader substrate specificity, such as D,L-endopeptidases . M23 peptidases contain two conserved catalytic motifs: H(x)nD and HxH, which coordinate a zinc ion . These enzymes play vital roles in bacterial physiology, including cell growth, division, and virulence, and have potential applications as antimicrobial agents against drug-resistant pathogens .

This domain is also found in Leukocyte cell-derived chemotaxin-2 homolog which is is required for the formation of somatosensory dendritic arbors.
RNA polymerase Rpc34-like (RNA_pol_Rpc34-like)
Type: Family

The entry represents a subunit specific of RNA Pol III, the tRNA specific polymerase. The C34 subunit of Saccharomyces cerevisiae RNA Pol III is part of a subcomplex of three subunits which have no counterpart in the other two nuclear RNA polymerases. This subunit interacts with TFIIIB70 and therefore participates in Pol III recruitment .

This entry also includes some homologus archaeal proteins of unknown function.
Proteasome beta-type subunit, conserved site (Proteasome_bsu_CS)
Type: Conserved_site

The proteasome (or macropain) (

) is a multicatalytic proteinase complex in eukaryotes and archaea, and in some bacteria, that seems to be involved in an ATP/ubiquitin-dependent nonlysosomal proteolytic pathway. In eukaryotes the proteasome is composed of 28 distinct subunits which form a highly ordered ring-shaped structure (20S ring) of about 700kDa. Most proteasome subunits can be classified, on the basis on sequence similarities into two groups, alpha (A) and beta (B). These are arranged in four rings of seven proteins, consisting of a ring of alpha subunits, two rings of beta subunits, and a ring of alpha subunits. In eukaryotes, each alpha and each beta ring consists of different proteins. Three of the beta subunits are peptidases in subfamily T1A, and each has a distinctive specificity (trypsin-like, chymotrypsin-like and glutamyl peptidase-like). The peptidases are N-terminal nucleophile hydrolases in which the N-terminal threonine is the nucleophile in the hydrolytic reaction . In the immunoproteasome, the catalytic components are replaced by three specialist, catalytic beta subunits . In bacteria and archaea there is only one alpha subunit and one beta subunit, and each ring is a homoseptamer.

This entry represents a conserved sequence region found in the N-terminal region of these proteins.
YgiW/YdeI (YgiW/YdeI)
Type: Family

This entry represents certain OB fold proteins involved in stress tolerance, including YgiW and YdeI, both of which are found in both Escherichia coli and Salmonella enterica, as well as more broadly . The characteristics of the protein distribution among the members of this entry suggest prophage matches in addition to the phage matches.

This family includes putative periplasmic proteins.