SII-SWORD/CoKE huggingface dataset:
Translation elongation factor EF1B, beta/delta chains, conserved site (Transl_elong_EF1B_B/D_CS)
Type: Conserved_site

Translation elongation factors are responsible for two main processes during protein synthesis on the ribosome . EF1A (or EF-Tu) is responsible for the selection and binding of the cognate aminoacyl-tRNA to the A-site (acceptor site) of the ribosome. EF2 (or EF-G) is responsible for the translocation of the peptidyl-tRNA from the A-site to the P-site (peptidyl-tRNA site) of the ribosome, thereby freeing the A-site for the next aminoacyl-tRNA to bind. Elongation factors are responsible for achieving accuracy of translation and both EF1A and EF2 are remarkably conserved throughout evolution.

Elongation factor EF1B (also known as EF-Ts or EF-1beta/gamma/delta) is a nucleotide exchange factor that is required to regenerate EF1A from its inactive form (EF1A-GDP) to its active form (EF1A-GTP). EF1A is then ready to interact with a new aminoacyl-tRNA to begin the cycle again. EF1B is more complex in eukaryotes than in bacteria, and can consist of three subunits: EF1B-alpha (or EF-1beta), EF1B-gamma (or EF-1gamma) and EF1B-beta (or EF-1delta) .

This entry represents the C-terminal region of the beta (EF-1beta or EF1B-alpha) and delta (EF-1delta or EF1B-beta) chains of EF1B proteins from eukaryotes and archaea. The beta and delta chains have exchange activity, which mainly resides in their homologous C-terminal regions. Their N-terminal regions may be involved in interactions with the gamma chain (EF-1gamma).
Peptidyl-tRNA hydrolase (Pept_tRNA_hydro)
Type: Family

Peptidyl-tRNA hydrolase (

) (PTH) is a bacterial enzyme that cleaves peptidyl-tRNA or N-acyl-aminoacyl-tRNA to yield free peptides or N-acyl-amino acids and tRNA. The natural substrate for this enzyme may be peptidyl-tRNA which drop off the ribosome during protein synthesis . Bacterial PTH has been found to be evolutionary related to a yeast protein . This enzyme is interesting as a potential target for the discovery of new antimicrobial agents as it is critical for the viability of bacteria [

}. It folds into a single α/β globular domain with seven β-strands forming a twisted mixed central β-sheet, surrounded by a total of six helices .

This group also contains chloroplast RNA splicing 2 (CRS2), which is closely related nuclear-encoded protein required for the splicing of nine group II introns in chloroplasts .
Glycoside hydrolase family 56, bee venom hyaluronidase (Venom_Hyaluronidase)
Type: Family

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

Family 56 (

) encompasses a group of hyaluronidases (

)
that includes venom hyaluronidases and mammalian sperm surface proteins (PH-20).

The venom of Apis mellifera (honeybee) contains several biologically-active peptides and
two enzymes, one of which is a hyaluronidase . The amino acid sequence of bee venom hyaluronidase contains 349 amino acids, and includes four
cysteines and a number of potential glycosylation sites . The sequence shows a high degree of similarity to PH-20, a membrane protein of mammalian
sperm involved in sperm-egg adhesion, supporting the view that hyaluronidases play a role in fertilisation .

This entry also includes a Tabanus yao protein, Tab y 2.0101, which can cause allergic reactions in humans .
Prenyltransferase alpha-alpha toroid domain (Prenyltrans)
Type: Domain

The entry includes enzymes involved in the biosynthesis of various terpenes and the prenylation of proteins . Terpene cyclases/mutases catalyse the cyclisation of squalene or oxidosqualene into various triterpenes, such as lanosterol, beta-amyrin, and hopene, which are crucial for sterol biosynthesis and other metabolic pathways. Protein prenyltransferase subunit beta enzymes facilitate the transfer of farnesyl or geranylgeranyl groups to specific cysteine residues in target proteins, which is essential for their proper localisation and function. These processes are vital for cellular functions, including membrane integrity, signal transduction, and stress responses.
Guanine-nucleotide dissociation stimulator, CDC24, conserved site (GDS_CDC24_CS)
Type: Conserved_site

Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP . The balance between the GTP bound (active) and GDP bound (inactive) states is regulated by the opposite action of proteins activating the GTPase activity and that of proteins which promote the loss of bound GDP and the uptake of fresh GTP . The latter proteins are known as guanine-nucleotide dissociation stimulators (GDSs) or also as guanine-nucleotide releasing (or exchange) factors (GRFs). Proteins that act as GDS can be classified into at least two families. One of these families is currently known to group the CDC24 family of proteins.
Arterivirus GP5 envelope glycoprotein (Arteri_GP5)
Type: Family

Arterivirus such as porcine reproductive and respiratory syndrome virus (PRRSV) contain four glycoproteins on the virion envelope: the major glycoprotein GP5 and minor glycoproteins GP2a, GP3, and GP4. GP5, previously known as Gl, is encoded in ORF5 and is 30- 45kDa in size . Gl is heterogeneously glycosylated with N-acetyllactosamine in a cell-type-specific manner. It is the most abundant envelope glycoprotein and a key target for neutralising antibodies .
Peptidase M32, carboxypeptidase Taq (Peptidase_M32_Taq)
Type: Family

This group of metallopeptidases belong to MEROPS peptidase family M32 (carboxypeptidase Taq family, clan MA(E)). The predicted active site residues for members of this family and thermolysin, the type example for clan MA, occur in the motif HEXXH.

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .
E6 early regulatory protein (E6)
Type: Family

The papillomavirus E6 oncoproteins are small zinc-binding proteins that share a conserved zinc-binding CXXC motif and do not have identified intrinsic enzymatic activity. E6 proteins are thought to act as adapter proteins, thereby altering the function of E6-associated cellular proteins. This model for E6 function is best supported by observations of human papillomavirus type 16 (HPV-16) E6 (16E6), which can alter the metabolism of the p53 tumor suppressor through association with a cellular E3 ubiquitin ligase called E6AP. HPV-16 E6 interacts with an 18-amino-acid sequence in E6AP, and in an as yet ill-defined fashion the E6AP-16E6 complex binds to p53, inducing the ubiquitin-dependent degradation of the trimolecular complex. 16E6 apparently functions as an adapter protein in the complex with p53, since E6AP does not interact with p53 in the absence of E6 and since the degradation of p53 requires both E6 and E6AP .

Despite the similarity in structure of the E6 oncoproteins, studies have indicated surprising biochemical diversity among E6 oncoproteins of different papillomavirus types. E6 from the cancer-associated human papillomaviruses (HPVs) complex with a cellular protein termed E6-AP and together with E6-AP bind to the p53 tumor suppressor protein thereby degrading p53 through ubiquitin-mediated proteolysis. E6 from the non-cancer-associated HPV types do not bind E6-AP or degrade p53. Bovine papilloma virus E6 (BE6) binds E6-AP but fails either to complex with p53 or to degrade associated proteins, implying that BE6 might transform cells through a mechanism different from that of the HPVs. In addition to targeting p53, E6 of both cancer-associated HPVs and BPV-1 have been shown to associate with a cellular-calcium-binding protein localized to the endoplasmic reticulum .
Tobacco mosaic virus-like, coat protein (TMV-like_coat)
Type: Family

This family contains virus coat proteins. Examples include those from Tobacco mosaic virus (TMV), Cucumber green mottle mosaic virus and Ribgrass mosaic virus (RMV).

In order to establish infections, viruses must be delivered to the cells of potential hosts and must then engage in activities that enable their genomes to be expressed and replicated. With most viruses, the events that precede the onset of production of progeny virus particles are referred to as the early events and, in the case of positive-strand RNA viruses, they include the initial interaction with and entry of host cells and the release (uncoating) of the genome from the virus particles. The uncoating process in TMV may involve the bidirectional release of coat protein subunits from the viral RNA which may be mediated by cotranslational and coreplicational disassembly mechanisms .

The TMV particle is assembled from its constituent coat protein and RNA by a complex process. The protein forms an obligatory intermediate (a cylindrical disk composed of two layers of protein units), which recognises a specific RNA hairpin sequence. This mechanism simultaneously fulfils the physical requirement for nucleating the growth of the helical particle and the biological requirement for specific recognition of the viral DNA .
Class I Hydrophobin (Class_I_Hydrophobin)
Type: Family

This entry represents class I hydrophobins found in fungi.

Hydrophobins are small, moderately hydrophobic extracellular proteins characterised by eight cysteine residues arranged in a strictly conserved motif. They are typically found on the outer surface of conidia and the hyphal wall, where they are thought to mediate contact and communication between the fungus and its environment . The hydrophobin family includes proteins such as cryparin, a cell surface-associated hydrophobin secreted by filamentous fungi ; cerato-ulmin, a secreted toxin implicated in Dutch elm disease ; and trihydrophobin from Claviceps fusiformis, which self-assembles at hydrophilic-hydrophobic interfaces on the hyphal surface . Hydrophobins are broadly categorised into two classes based on their solubility and assembly properties. Class I hydrophobins form rodlet bundles that coat aerial cell surfaces and contribute to cellular hydrophobicity, supporting fungal growth, development, and dispersal. In contrast, Class II hydrophobins form highly ordered films at water-air interfaces via intermolecular interactions but do not form rodlet structures. Hyd1 is a class II hydrophobin that not only fulfils structural roles but also functions as an elicitor of induced systemic resistance (ISR) in plants. During interaction with maize, Hyd1 binds the host target protein UBL and recruits additional UBL proteins in the roots, triggering defence responses such as cell death and activation of brassinosteroid, jasmonate (JA), and ethylene (ET) signalling pathways .
mRNA capping enzyme, adenylation domain (mRNA_cap_enzyme_adenylation)
Type: Domain

This entry represents the adenylation domain of the mRNA capping enzyme . The mRNA-capping enzyme is composed of two separate chains alpha and beta, respectively a mRNA guanylyltransferase and an RNA 5'-triphosphatase . Binding of the enzyme to nucleotides is specific to the GMP moiety of GTP. The viral mRNA capping enzyme is a monomer that transfers a GMP cap onto the end of mRNA that terminates with a 5'-diphosphate tail.

It contains a catalytic core composed of an adenylation domain and a C-terminal OB-fold domain containing conserved sequence motifs. The adenylation domain binds ATP and contains many active site residues .
Aspartate kinase (Asp_kinase)
Type: Family

Bacteria, plants and fungi metabolise aspartic acid to produce four amino acids -lysine, threonine, methionine and isoleucine -in a series of reactions known as the aspartate pathway. Additionally, several important metabolic intermediates are produced by these reactions, such as diaminopimelic acid, an essential component of bacterial cell wall biosynthesis, and dipicolinic acid, which is involved in sporulation in Gram-positive bacteria. Members of the animal kingdom do not posses this pathway and must therefore acquire these essential amino acids through their diet. Research into improving the metabolic flux through this pathway has the potential to increase the yield of the essential amino acids in important crops, thus improving their nutritional value. Additionally, since the enzymes are not present in animals, inhibitors of them are promising targets for the development of novel antibiotics and herbicides. For more information see .

Aspartate kinase (

) (AK) catalyzes the first reaction in the aspartate pathway; the phosphorylation of aspartate. The product of this reaction can then be used in the biosynthesis of lysine or in the pathway leading to homoserine, which participates in the biosynthesis of threonine, isoleucine and methionine .

In bacteria there are three different aspartate kinase isozymes which differ in sensitivity to repression and inhibition by Lys, Met and Thr. AK1 and AK2 are bifunctional enzymes which both consist of an N-terminal AK domain and a C-terminal homoserine dehydrogenase domain. AK1 is involved in threonine biosynthesis and AK2, in that of methionine. The third isozyme, AK3 is monofunctional and involved in lysine synthesis. In archaea and plants there may be a single isozyme of AK which in plants is multifunctional.
Homoserine dehydrogenase, catalytic (HDH_cat)
Type: Domain

This entry represents the catalytic domain of homoserine dehydrogenase.

Homoserine dehydrogenase (

) catalyses the third step in the aspartate pathway; the NAD(P)-dependent reduction of aspartate beta-semialdehyde into homoserine . Homoserine is an intermediate in the biosynthesis of threonine, isoleucine, and methionine. The enzyme can be found in a monofunctional form, in some bacteria and yeast, or a bifunctional form consisting of an N-terminal aspartokinase domain and a C-terminal homoserine dehydrogenase domain, as found in bacteria such as Escherichia coli and in plants. Structural analysis of the yeast monofunctional enzyme (

) indicates that the enzyme is a dimer composed of three distinct regions; an N-terminal nucleotide-binding domain, a short central dimerisation region, and a C-terminal catalytic domain . The N-terminal domain forms a modified Rossman fold, while the catalytic domain forms a novel α-β mixed sheet.

Bacteria, plants and fungi metabolise aspartic acid to produce four amino acids -lysine, threonine, methionine and isoleucine -in a series of reactions known as the aspartate pathway. Additionally, several important metabolic intermediates are produced by these reactions, such as diaminopimelic acid, an essential component of bacterial cell wall biosynthesis, and dipicolinic acid, which is involved in sporulation in Gram-positive bacteria. Members of the animal kingdom do not posses this pathway and must therefore acquire these essential amino acids through their diet. Research into improving the metabolic flux through this pathway has the potential to increase the yield of the essential amino acids in important crops, thus improving their nutritional value. Additionally, since the enzymes are not present in animals, inhibitors of them are promising targets for the development of novel antibiotics and herbicides. For more information see .
RTX calcium-binding nonapeptide repeat (Hemolysn_Ca-bd)
Type: Repeat

Gram-negative bacteria produce a number of proteins that are secreted into the growth medium by a mechanism by the type I secretion system that does not require a cleaved N-terminal signal sequence. These proteins, while having different functions, share two properties: they bind calcium and they contain a multiple tandem repeat of a nonapeptide . The nonapeptide is found in a group of bacterial exported proteins that includes haemolysin, cyclolysin, leukotoxin and metallopeptidases belonging to MEROPS peptidase family M10 (clan MA(M)), subfamily 10B (serralysin).

It has been suggested that the internally repeated domain of haemolysin may be involved in Ca-mediated binding to erythrocytes. It has been shown that such a domain is involved in the binding of calcium ions in a parallel β roll structure .

The
Bordetella pertussis
adenylate cyclase toxin tertiary structure has been solved. The C-terminal RTX repeats are Asp-rich, which bind calcium ions as the protein moves from the low calcium intercellular environment to a higher extracellular concentration of calcium ions. The C-terminal assembly containing the RTX repeats has been shown to form β-rolls, which prevent backsliding of the protein in the type I secretion system conduits and accelerating secretion of the large toxin .
Chlorophyll A-B binding protein, plant and chromista (Chloro_AB-bd_pln)
Type: Family

The light-harvesting complex (LHC) consists of chlorophylls A and B and the chlorophyll A-B binding protein. LHC functions as a light receptor that captures and delivers excitation energy to photosystems I and II with which it is closely associated. Under changing light conditions, the reversible phosphorylation of light harvesting chlorophyll a/b binding proteins (LHCII) represents a system for balancing the excitation energy between the two photosystems .

The N terminus of the chlorophyll A-B binding protein extends into the stroma where it is involved with adhesion of granal membranes and photo-regulated by reversible phosphorylation of its threonine residues . Both these processes are believed to mediate the distribution of excitation energy between photosystems I and II.

This family also includes the photosystem II protein PsbS, which plays a role in energy-dependent quenching that increases thermal dissipation of excess absorbed light energy in the photosystem .

This entry is limited to plant and chromista proteins.
Phosphoglycerate/bisphosphoglycerate mutase, active site (PG/BPGM_mutase_AS)
Type: Active_site

Phosphoglycerate mutase (

) (PGAM) and bisphosphoglycerate mutase (

)
(BPGM) are structurally related enzymes that catalyse reactions involving the transfer of phospho groups between the three carbon atoms of phosphoglycerate . Both enzymes can catalyse three different reactions with different specificities, the isomerization of 2-phosphoglycerate (2-PGA) to 3-phosphoglycerate (3-PGA) with 2,3-diphosphoglycerate (2,3-DPG) as the primer of the reaction, the synthesis of 2,3-DPG from 1,3-DPG with 3-PGA as a primer and the degradation of 2,3-DPG to 3-PGA (phosphatase

activity).

In mammals, PGAM is a dimeric protein with two isoforms, the M (muscle) and B (brain) forms. In yeast, PGAM is a tetrameric protein.

BPGM is a dimeric protein and is found mainly in erythrocytes where it plays a major role in regulating haemoglobin oxygen affinity as a consequence of controlling 2,3-DPG concentration. The catalytic mechanism of both PGAM and BPGM involves the formation of a phosphohistidine intermediate .

A number of other proteins including, the bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase that catalyses both the synthesis and the degradation of fructose-2,6-bisphosphate and bacterial alpha-ribazole-5'-phosphate phosphatase, which is involved in cobalamin biosynthesis, belong to this family .

This entry contains the active site phosphohistidine residue.
Interferon regulatory factor, DNA-binding domain (Interferon_reg_fact_DNA-bd_dom)
Type: Domain

Viral infections induce the expression of type I interferons (IFN-alpha and IFN-beta) genes. The induction is due to the transcriptional activation of the IFN genes. Interferon regulatory factor I (IRF-1) is one of the transcription factors responsible for that activation. IRF-1 binds to an upstream regulatory cis element, known as the interferon consensus sequence (ICS), which is found in the promoters of type I IFN and IFN-inducible MHC class I genes. Interferon regulatory factor 2 (IRF-2) is a protein that also interacts with the ICS, but that does not function as an activator; rather, it suppresses the function of IRF-1 under certain circumstances .

These proteins share a highly conserved N-terminal domain of about 100 amino acid residues which is involved in DNA-binding and which contain five conserved tryptophans. This domain is known as a 'tryptophan pentad repeat' or a 'tryptophan cluster' and is also present in:

Interferon consensus sequence binding protein (ICSBP) , a transcription factor expressed predominantly in lymphoid tissues and induced by IFN-gamma that also binds to the ICS.

Transcriptional regulator ISGF3 gamma subunit . ISGF3 is responsible for the initial stimulation of interferon-alpha-responsive genes. It recognises and binds to the interferon-stimulated response element (ISRE) within the regulatory sequences of target genes.

Interferon regulatory factor 3 (IRF-3).

Interferon regulatory factor 4 (IRF-4) which binds to the interferon- stimulated response element (ISRE) of the MHC class I promoter.

Interferon regulatory factor 5 (IRF-5).

Interferon regulatory factor 6 (IRF-6).

Interferon regulatory factor 7 (IRF-7).

Gamma Herpesviruses vIRF-1, -2 and -3, proteins with homology to the cellular transcription factors of the IRF family . Neither vIRF-1 nor vIRF-2 bind to DNA with the same specificity as cellular IRFs, indicating that if vIRFs are DNA-binding proteins, their binding has a pattern distinct from that of the cellular IRFs. Whether vIRF-3 can bind DNA with the same specificity as cellular IRFs is not known.

The IRF tryptophan pentad repeat DNA-binding domain has an α/β architecture comprising a cluster of three α-helices (alpha1-alpha3) flanked on one side by a mixed four-stranded β-sheet (beta1-beta4). It forms a helix-turn-helix motif that binds to ISRE consensus sequences found in target promoters. Three of the tryptophan residues contact DNA by recognising a GAAA sequence .

This entry represents the IRF tryptophan pentad repeat DNA-binding domain.
SIS domain (SIS_dom)
Type: Domain

The sugar isomerase (SIS) domain is a phosphosugar-binding module that is found in a variety of eubacterial, archaebacterial and eukaryotic proteins
that have a role in phosphosugar isomerization or regulation . In enzymes, the SIS domain can have a catalytic function as an isomerase and bind to phosphorylated sugars. In bacterial transcriptional regulators of the rpiR family, the domain seems to bind substrates implicated in the genes for sugar metabolism that are controlled by the regulator. The SIS domain is found in one or two copies and can be linked to additional domains, such as helix-turn-helix (HTH), CBS, glutamine amidotransferases type 2, or phosphopantetheine-attachment .

The SIS domain has an α-β structure and is dominated by a five-stranded parallel β-sheet flanked on either side by α-helices forming a three-layer α-β-α sandwich . The fold shows similarities to that of glucose-6-phosphate isomerase.