SII-SWORD/CoKE huggingface dataset:
Anti-restriction Endonuclease Superfamily (Anti-Restrict_Endo_sf)
Type: Homologous_superfamily

This superfamily of proteins includes enzymes that interact with host cell DNA to counteract restriction-modification systems. Members of this superfamily function by inhibiting host endonucleases that are specific for modified cytosine residues within DNA. These proteins are involved in protecting invading genetic elements, such as phage DNA, from host defense mechanisms by blocking the cleavage of methylated or hydroxymethylated cytosines in specific DNA sequences. Their activity ensures the survival of the genetic material they are associated with by preventing its degradation by the host's restriction enzymes.
Carboxypeptidase A Inhibitor I44 (CPA_Inhibitor_I44)
Type: Homologous_superfamily

This superfamily of proteins includes members that function as inhibitors of carboxypeptidase A, an enzyme involved in the processing and maturation of proteins by removing amino acids from the carboxy terminus of peptides. Members of this superfamily are characterized by their ability to regulate the activity of carboxypeptidase A, thereby influencing protein turnover and maintaining homeostasis within the cell. The proteins in this superfamily share structural similarities that underpin their inhibitory function, reflecting a common evolutionary origin and a specialized role in protease inhibition.
CDI System Immunity Component (CDI_Immunity_Comp)
Type: Homologous_superfamily

This superfamily of proteins encompasses immunity components within toxin-immunity modules, which are implicated in contact-dependent growth inhibition (CDI) systems. These systems enable bacteria to interact with and suppress the proliferation of closely related bacteria upon direct contact. Members of this superfamily are responsible for neutralizing the toxic effects of cognate toxins, thereby providing a defense mechanism against CDI-mediated inhibition. The proteins function by specifically counteracting the activity of associated toxins, which are often encoded within the same genetic locus. The protective role of these proteins is crucial in bacterial competition and survival, as they can confer immunity against the toxic effects of homologous toxins produced by other bacteria in their vicinity.
Benzylsuccinate Synthase-like (BSS-like_sf)
Type: Homologous_superfamily

This superfamily of proteins is involved in the enzymatic addition of fumarate to aromatic hydrocarbons, a key step in anaerobic toluene degradation. Members of this superfamily function as part of a multi-subunit enzyme complex, catalyzing the initial reaction in the anaerobic breakdown of toluene to benzylsuccinate. The enzymatic activity is regulated by specific activating enzymes and is sensitive to oxygen, which can rapidly inactivate the enzyme. This indicates a role in anaerobic metabolic processes, particularly in environments where oxygen is scarce or absent.
Leguminous Lectin Domain-containing Protein (Leguminous_Lectin_Domain_sf)
Type: Homologous_superfamily

This superfamily of proteins is characterized by its ability to bind specific carbohydrate molecules. Members of this superfamily are involved in various biological processes, including cell-cell recognition, signaling, and host-pathogen interactions. They typically recognize and bind to mannose or glucose moieties, which can be present on the surface of cells or as free sugars. The binding of these lectins to carbohydrates can trigger various cellular responses or facilitate interactions between cells. Due to their carbohydrate-binding properties, these proteins play a crucial role in the immune response and are involved in the recognition of glycoproteins and glycolipids.
Toxin-Substrate Binding Inhibitor (Toxin-Sub_Inhibitor_sf)
Type: Homologous_superfamily

This superfamily of proteins includes immunity components that are involved in the inhibition of early activation of associated toxins. Members of this superfamily function by binding to the toxin's substrate binding site, thereby blocking the entry of the substrate and preventing the toxin's deleterious activity. This protective mechanism is crucial for the survival of the organisms that produce these toxins, ensuring that the toxins do not inadvertently damage the producing organism itself.
Type III Secretion System Regulatory Protein (T3SS_Regulatory_Protein)
Type: Homologous_superfamily

This superfamily of proteins includes regulatory components that modulate the expression of type III secretion systems (T3SS) in bacteria. Members of this superfamily function as key regulators by interacting with other proteins to control the secretion machinery's activity. In non-inducing conditions, they maintain the T3SS in a dormant state by participating in a complex that sequesters transcriptional activators. Upon receiving specific environmental signals, such as host cell contact or low calcium levels, these proteins can be secreted, altering the complex's composition and freeing the transcriptional activator to initiate the expression of T3SS genes. This regulatory mechanism ensures that the secretion system is activated only in response to appropriate stimuli, which is crucial for the pathogenicity and survival of the bacteria.
Cell Envelope Biogenesis-Associated Superfamily (CellEnv_BiogenAssoc_sf)
Type: Homologous_superfamily

This superfamily of proteins is involved in the bacterial cell envelope biogenesis. Members of this superfamily are typically associated with the assembly and maintenance of the outer membrane, playing a role in the transport and incorporation of cell wall components. They may interact with other proteins or complexes involved in the synthesis and export of cell envelope constituents, contributing to the structural integrity and function of the bacterial outer membrane.
Antimicrobial Activity and Nucleic Acid-Binding Superfamily (Antimicro_NucAcidBind_sf)
Type: Homologous_superfamily

This superfamily of proteins includes members with antimicrobial activity, specifically targeting certain bacterial plant pathogens. They are capable of inhibiting the growth of bacteria such as Xanthomonas oryzae pv. oryzae and Ralstonia solanacearum. These proteins may also interact with nucleic acids, potentially binding to DNA or mRNA, which could suggest a role in regulating gene expression or interfering with bacterial replication mechanisms. The precise mode of action for the antimicrobial effect and nucleic acid binding, however, may vary among different family members.
Vaterite Nucleation and Antimicrobial Superfamily (Vaterite_Nuc_Antimicrob_sf)
Type: Homologous_superfamily

This superfamily of proteins is involved in the biomineralization process, specifically in the nucleation and stabilization of vaterite, a crystalline form of calcium carbonate. Members of this superfamily possess antimicrobial properties, effective against certain bacterial pathogens including Pseudomonas aeruginosa and Proteus vulgaris.
Antifreeze Alpha-Hairpin Domain-Containing Protein (AFP_Alpha-Hairpin_sf)
Type: Homologous_superfamily

This superfamily of proteins is involved in the protection of organisms in cold environments by inhibiting ice crystal growth. Members of this superfamily are characterized by their ability to lower the freezing point of bodily fluids, such as blood, in a concentration-dependent manner. They achieve this by binding to ice crystals, preventing their further growth. The structure of these proteins typically includes an alpha-hairpin configuration, with a distinctive repeating pattern that contributes to their antifreeze properties. The proteins are known to contain a significant amount of ordered water molecules within their core, which is thought to play a crucial role in their interaction with ice surfaces. This interaction is likely facilitated by the protrusion of these bound water molecules between the helices, allowing for the modulation of ice crystal formation.
Intense Sweet-Taste Modifier (Sweet-Taste_Mod_sf)
Type: Homologous_superfamily

This superfamily of proteins includes members that are known for their role in modifying taste perception. They are characterized by their ability to elicit a sweet taste sensation, which is significantly more intense than that of common sugars. These proteins interact with taste receptors on the tongue to induce sweetness, often at very low concentrations. Their unique taste-modifying properties make them of interest for various applications in the food industry, particularly as high-intensity natural sweeteners or as part of sugar substitutes in dietary products.
Endolysin PlyC small cell-wall binding subunit superfamily (PlyC_sf)
Type: Homologous_superfamily

This superfamily of proteins includes components involved in bacterial cell lysis, particularly during bacteriophage infection. Members of this superfamily function in the degradation of host peptidoglycans, a critical step in the release of mature viral particles from the host cell. They are typically activated following the permeabilization of the host cell membrane by another protein, such as a holin. These proteins then access the periplasmic space to degrade the peptidoglycan layer. A characteristic feature of this superfamily is the presence of a subunit responsible for specific binding to the host cell wall, which is essential for the lytic activity. The binding often targets specific carbohydrates on the surface of the host bacteria, and this interaction is a prerequisite for the subsequent cell lysis.

This entry includes PlyC, an enzyme specific for streptococcal species. PlyC consists of a single PlyCA catalytic subunit in complex with eight PlyCB molecules arranged in a planar octameric ring. One surface of the PlyCB octamer is quite planar, whereas the other is more convex in shape. The bacterial cell wall binding is achieved through a cleft on PlyCB, which interacts strongly with phosphatidylserine so that PlyC can cross the epithelial cell membrane
Metal-binding blue pigment complex (MB_blue_pigment_sf)
Type: Homologous_superfamily

This superfamily of proteins includes members that are known for their unique blue coloration, which is attributed to a dimeric protein-pigment complex. The proteins in this superfamily are characterized by their ability to bind metal ions, which is critical for the stabilization of the blue pigment and for the protein's structural integrity. The metal-binding property of these proteins is facilitated by a specific arrangement of amino acids that coordinate the metal ions. This function is significant in the context of biological systems where metal ion binding is essential for various biochemical processes. The proteins may also play a role in the protection against oxidative stress, given their potential to interact with reactive oxygen species through the bound metal ions.
Ciprofloxacin tolerance protein (AciT)
Type: Family

This entry represents the AciT ciprofloxacin tolerance protein found mainly in Moraxellaceae. This is likely localised at the cell membrane. Disruption of this gene results in higher susceptibility to ciprofloxacin. AciT (

) is essential for tolerance to ciprofloxacin, likely by enabling filamentation in response to the antibiotic .
FBD-associated F-box protein At1g61320/At1g61330-like (At1g61320/At1g61330-like)
Type: Family

This entry includes a group of plant proteins such as FBD-associated F-box protein At1g61320 and At1g61330 from Arabidopsis thaliana. These proteins contain a F-box motif, which is typically involved in protein-protein interactions. The F-box motif is a key component of the SCF (SKP1-cullin-F-box) complex, which functions as an E3 ubiquitin ligase. Proteins in this family are likely to play a role in the ubiquitination pathway, where they are responsible for targeting specific substrates for proteasomal degradation. This process is crucial for various cellular functions, including cell cycle regulation, signal transduction, and transcriptional regulation. The F-box domain facilitates the recognition and binding of substrate proteins, while other domains present in these proteins, such as the FBD (F-box associated domain), may contribute to the specificity and functionality of the SCF complex .
Vpar_1526-like (Vpar_1526-like)
Type: Family

This family represents the homologues of Vpar_1526 protein from Veillonella parvula, that was proposed to be an inner membrane protein . It is predicted to fold into a mainly α-helical structure.
Phenol regulator MopR (MopR)
Type: Family

This entry represents a group of proteins from Acinetobacter, including MopR from Acinetobacter guillouiae, which is involved in the regulation of the phenol degradation pathway. This NtrC-related sigma-54-dependent transcriptional activator activates phenol hydroxylase expression in the presence of phenol . The sequence, over 500 amino acids in length, includes a hydrocarbon-binding V4R sensor domain (see

).
Tungstate-binding protein TupA (TupA)
Type: Family

This entry represents a group of proteins from Campylobacterales, including Tungstate-binding protein TupA from Campylobacter jejuni, part of an ABC transporter complex involved in ultra-high affinity tungstate uptake. It specifically binds tungstate .
Tungstate uptake system permease protein TupB (TupB)
Type: Family

This entry represents a group of proteins from Campylobacter, including Tungstate uptake system permease protein TupB from Campylobacter jejuni, part of an ABC transporter complex involved in ultra-high affinity tungstate uptake. It is probably responsible for the translocation of the substrate across the membrane .
Galactofuranose transporter permease protein YtfT (YtfT)
Type: Family

This entry represents a group of proteins from Enterobacterales, including Galactofuranose transporter permease protein YtfT from Escherichia coli, which is thought to be part of the ABC transporter complex, YtfQRT-YjfF, involved in galactofuranose transport.
Polyketide synthase Pks13 (Pks13)
Type: Family

This entry represents a group of proteins from Mycobacteriales, including Polyketide synthase Pks13 from Mycobacterium tuberculosis whicch is involved in the biosynthesis of mycolic acids .
Gephyrin-like molybdotransferase receptor GlpR (GlpR)
Type: Family

This entry represents a group of proteins from actinomycetes, including GlpR from Corynebacterium glutamicum (

). Eukaryotic gephyrin-like molybdotransferase Glp and its membrane receptor GlpR bind to FtsZ and Wag31 to form a tight protein complex, which plays an important role in divisome-elongasome transition during cytokinesis in Corynebacteriales .
Gp66-like (Gp66-like)
Type: Family

This entry represents Gp66 from Stanholtvirus sv1026b (

) and similar uncharacterised bacterial sequences.
F-box/LRR-repeat protein 13-like, F-box domain (F-box_AtFBL13-like)
Type: Domain

This entry includes F-box/LRR-repeat protein 13 (AtARP13) form Arabidopsis thaliana, which belongs to the largest subfamily of plant F-box proteins, F-box/LRR-repeat proteins (FBLs). It contains tandem leucine-rich repeats (LRRs) following the F-box domain at the N-terminal. Like other F-box proteins, they may be components of SCF (Skp1 Cdc53 F-box protein) E3 ubiquitin ligase complexes, which may mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The F-box domain, represented in this entry, has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression .
Conjugal transfer protein TraW-like (TraW-like)
Type: Family

Members of this family represent conjugal plasmid transfer proteins, including TraW, predominantly found in proteobacteria. The term conjugal plasmid transfer is used for certain transfer systems, including that of IncI1 family plasmids. Note that an unrelated protein, also designated TraW, participates in the assembly of F-pilin subunits, involved in transfer of F-plasmids.
Dockerin-like domain (Dockerin_dom_GC-type)
Type: Domain

This entry represents a domain often found at the C-terminal end of a group of bacterial proteins that begins and ends with a near invariant C, and GC, respectively. Members of this entry are mainly found in metagenome-assembled genomes of the taxonomic class Phycisphaerae, within the Planctomycetota. It shows sequence homology to the type I dockerin domain (see

), which likewise contains an internal repeat and which appears in strictly C-terminal positions of otherwise unrelated proteins. Type I dockerin domains occur in proteins that are organised by interaction with the cohesin domain (

) in order to form the cellulosome. However, the GC-type dockerin domain described here is uncharacterised.
Choice-of-anchor U domain (Choice_anch_U_dom)
Type: Domain

The uncharacterised choice-of-anchor U domain is found in a group of prokaryotic proteins.
PhaP6-like (PhaP6-like)
Type: Family

This entry represents a group of proteins from proteobacteria, including PhaP6 from Cupriavidus necator (H16_B1988,

), a phasin with no visible effect on formation of PHB granules .
LEPRxLL conserved site (LEPRxLL_CS)
Type: Conserved_site

This conserved site, which is about 24 amino acids long and contains the LEPRxLL motif, is found at the N-terminal of a group of bacterial repeat-filled giant proteins. Member proteins average over 8000 amino acids.
Autotransporter-associated N-terminal domain (Autotransptr-assoc_N)
Type: Domain

This domain is found at the N-terminal of a group of large autotransporter proteins from Fusobacteriales. Many members of this group show an autotransporter beta-domain (

) at the C-terminal end. In paralogous families of such proteins, the N-terminal and C-terminal regions are fairly well-conserved, but the repetitive central region is poorly conserved in both length and sequence.
CPC_1213-like (CPC_1213-like)
Type: Family

This entry represents a family of small uncharacterised proteins found in Firmicutes. They are probably intrinsically disordered. Their function is unknown.
Plasmid transfer protein TraA-like (TraA-like)
Type: Family

This entry represents uncharacterised proteins found mainly in Actinomycetes. These proteins are related to TraA plasmid transfer protein identified in Streptomyces plasmid pSN22, originating from Streptomyces nigrifaciens .
Pyrroline-5-carboxylate reductase-like conserved site (P5CR-like_CS)
Type: Conserved_site

Pyrroline-5-carboxylate reductase (P5CR) (

) is the enzyme that catalyses the terminal step in the biosynthesis of proline from glutamate, the NAD(P) dependent oxidation of 1-pyrroline-5-carboxylate intoproline. This enzyme is also able to convert delta-1-piperideine-6-carboxylate (P6C) into pipecolic acid ; this activity is part of pathway for the biosynthesis of the cyclic tetrapeptide apicidin F in the fungus Fusarium fujikuroi .

This entry also includes Delta-1-pyrroline-5-carboxylate reductase kk1I part of the gene cluster that mediates the biosynthesis of KK-1, a novel cyclic depsipeptide with 10 residues which is a promising active compound with high activity against many plant pathogens, especially Botrytis cinerea .

The sequences of P5CR from eubacteria (gene proC), archaebacteria and eukaryotes show only a moderate level of overall similarity. This entry represents the best conserved region located in the C-terminal section of P5CR.
Trichothecene efflux pump Tri12 (MFS_Tri12-like)
Type: Family

This family includes Fusarium sporotrichioides trichothecene efflux pump (TRI12), which may play a role in the species self-protection against trichothecenes. TRI12 belongs to the Major Facilitator Superfamily (MFS) of membrane transport proteins, which are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement .
ATP P2X receptor, conserved site (P2X_RECEPTOR_CS)
Type: Conserved_site

This entry represents a conserved region in P2X purinoceptors, located in the central part of the extracellular domain, which contains two of the conserved cysteines.

P2X purinoceptors are cation-selective ion channels that open on binding to extracellular ATP; they play a role in fast synaptic transmission between neurons, and from autonomic nerves to smooth muscles . When ATP is released as a neurotransmitter from central and peripheral nerves, it acts at P2X receptors to produce postsynaptic depolarization and excitation.

P2X purinoceptors are cell membrane ion channels, gated by adenosine 5'-triphosphate (ATP) and other nucleotides; they have been found to be widely expressed on mammalian cells, and, by means of their functional properties, can be differentiated into three sub-groups. The first group is almost equally well activated by ATP and its analogue alpha,betamethylene-ATP, whereas, the second group is not activated by the latter compound. A third type of receptor (also called P2Z) is distinguished by the fact that repeated or prolonged agonist application leads to the opening of much larger pores, allowing large molecules to traverse the cell membrane. This increased permeability rapidly leads to cell death, and lysis.

Molecular cloning studies have identified seven P2X receptor subtypes, designated P2XR1-P2XR7, however, P2X1R, P2X2R, P2X3R, P2X4R, and P2X7R are functional . These receptors are proteins that share 35-48% amino acid identity, and possess two putative transmembrane (TM) domains, separated by a long (~270 residues) intervening sequence, which is thought to form an extracellular loop. Around 1/4 of the residues within the loop are invariant between the cloned subtypes, including 10 characteristic cysteines.

Studies of the functional properties of heterologously expressed P2X receptors, together with the examination of their distribution in native tissues, suggests they likely occur as both homo-and hetero multimers in vivo . Stimulation of these receptors induces changes in intracellular ion homeostasis leading to multiple key responses crucial for initiation, propagation, and resolution of inflammation . The P2X7 subtype has an important role in the activation of lymphocyte, granulocyte, macrophage and dendritic cell responses and, therefor, it may be a promising target for anti-inflammatory therapies.
PB1-like domain (PB1-like)
Type: Domain

The PB1 (Phox and Bem1) domain, comprising about 80 amino acid residues, is conserved among animals, fungi, amoebas, and plants. It functions as a protein binding module through PB1-mediated heterodimerization or homo-oligomerization . The PB1 domain is found in several signaling proteins including:

- Mammalian MEK5, a MAP kinase kinase implicated in epidermal growth factor-induced cell proliferation.

- Mammalian Sequestosome-1 (Sqstm1) or p62/ZIP, a protein linking the zeta isoform of protein kinase C to RIP and/or potassium channels.

- Mammalian neutrophil cytosol factor 4 (NCF-4) or p40(phox), a cytosolic factor of the superoxide-generating NADPH oxidase in phagocytes.

- Mammalian neutrophil cytosol factor 2 (NCF-2) or p67(phox), an oxidase activator.

- Yeast bud emergence protein 1 (Bem1), necessary for cell polarization during vegetative growth.

- Yeast cell division control protein 24 (CDC24), a guanine nucleotide exchange factor (GEF) for the small GTPase CDC42.

- Plant AUXIN RESPONSE FACTOR (ARF) transcription factor family, regulates gene expression in response to auxin.

The PB1 domains adopt an ubiquitin-like β-grasp fold, containing two α-helices and a mixed five-stranded β-sheet. PB1 domains may display an acidic surface (type I), a basic surface (tape II), or both surfaces (type I/II) on opposite faces of the domain structure to allow for front-to-back orientation of multiple PB1 domains .
A-adding tRNA nucleotidyltransferase (A-adding_TNT)
Type: Family

This entry represents a family of proteins from Geobacteraceae, including A-adding tRNA nucleotidyltransferase from Geobacter sulfurreducens, which is involved in the synthesis of the tRNA CCA terminus. It adds the terminal adenosine residue to tRNA .
HTH-type transcriptional regulator lrs14 (Lrs14)
Type: Family

This entry represents a group of archaeal proteins, including HTH-type transcriptional regulator lrs14 from Saccharolobus solfataricus, which acts in transcription regulation. It binds to multiple sequences in its own promoter .