SII-SWORD/CoKE huggingface dataset:
Sprouty domain-containing protein (Sprouty_domain)
Type: Family

This family of proteins functions as modulators of cellular signaling pathways, particularly those mediated by fibroblast growth factors (FGFs) and epidermal growth factor receptor (EGFR). Members of this family are known to inhibit FGF-induced differentiation processes, such as retinal lens fiber differentiation, and to suppress various aspects of the MAPK signaling cascade. They play roles in preventing epithelial-to-mesenchymal transition in response to transforming growth factor-beta (TGFB) and can negatively regulate organogenesis and cell growth. Some family members also interfere with integrin-mediated cell spreading and may inhibit ubiquitination processes associated with EGFR.
G-protein coupled endothelin receptor (GPCR_endothelin_rcpt)
Type: Family

This family of proteins includes receptors that are part of the G-protein coupled receptor 1 superfamily. They specifically belong to the endothelin receptor subfamily, which is characterized by their ability to bind endothelin molecules. Members of this family are involved in various physiological processes by mediating the action of endothelins through G protein-associated signaling pathways that lead to the activation of a phosphatidylinositol-calcium second messenger system. These receptors have distinct binding affinities for different endothelin isoforms, with some showing a preference for endothelin-1 and others being non-specific, binding to endothelin 1, 2, and 3. They play crucial roles in cardiovascular function, development, and homeostasis.
Fungal stress response NST1 (Fungal_stress_NST1)
Type: Family

The NST1 family comprises stress response proteins that are implicated in the regulation of salt tolerance. Members of the NST1 family are suggested to function as negative regulators of salt tolerance, potentially playing a role in the cellular response to high salinity conditions. In some species, proteins from the NST1 family are known to act in conjunction with other proteins, such as MSL1, to exert their regulatory function. The consistent presence of NST1 family members across various fungal species indicates a conserved role in stress response mechanisms, particularly in the context of osmotic stress.
RSAD2 and Viperin antiviral (RSAD2/Viperin_antiviral)
Type: Family

The RSAD2 and Viperin protein family includes enzymes that are involved in the antiviral response of cells. Members of this family catalyze the conversion of nucleotides such as CTP, GTP, and UTP to their dehydrated forms via a SAM-dependent radical mechanism. These modified nucleotides act as chain terminators for viral RNA polymerases, thereby inhibiting viral replication. The family plays a crucial role in the antiviral state induced by interferons and can also modulate immune responses, such as facilitating T-cell activation and differentiation. Some family members are involved in the ubiquitination process that leads to IFN-beta production in dendritic cells. Additionally, certain bacterial members confer resistance to phages by blocking viral polymerase transcription.
Extracellular matrix-binding protein (ECM-binding_protein)
Type: Family

This family of proteins is involved in bacterial adhesion processes. Members of this family have been shown to promote bacterial attachment to fibronectin, a glycoprotein that exists in soluble and fibrous forms and plays a critical role in cell adhesion, growth, migration, and differentiation. The interaction with fibronectin is dose-dependent and saturable, indicating a specific binding mechanism. Through this interaction, the proteins may facilitate the colonization of host tissues and contribute to the pathogenesis of bacterial infections by stabilizing the attachment of bacteria to host cells and extracellular matrix components.
Tetrapyrrole and Bacteriochlorophyll Biosynthesis Methyltransferases (Tetrapyrrole_Bchl_Biosynth_MTs)
Type: Family

The BchE and radical SAM superfamily proteins are involved in diverse biosynthetic pathways, including the formation of tetrapyrroles and bacteriochlorophylls, essential components for photosynthesis and light-harvesting in certain bacteria. The BchE family members catalyze the formation of the isocyclic E-ring in Mg-protoporphyrin monomethyl ester, leading to protochlorophyllide a, a precursor to chlorophyll. The radical SAM superfamily proteins perform methylation reactions, such as the methylation of hopanoids and the biosynthesis of bacteriochlorophyll c, which is crucial for green sulfur bacteria in low-light conditions. Other members are involved in antibiotic biosynthesis, fosfomycin production, and modification of other organic compounds, indicating a broad functional spectrum related to methylation processes.
Lipopolysaccharide/Lipooligosaccharide Heptosyltransferase (LPS_LOS_Heptosyltrfase)
Type: Family

The glycosyltransferase 9 family is involved in the biosynthesis of the core oligosaccharide region of lipopolysaccharides (LPS) and lipooligosaccharides (LOS). Members of this family catalyze the addition of heptose units to the Kdo2-lipid A module, which is a critical step in the formation of the LPS and LOS structures. These enzymes are responsible for transferring the first, second, or third heptose unit, depending on the specific protein, to the growing oligosaccharide chain. Some members can also glycosylate autotransporter proteins, contributing to bacterial adhesion to host cells. The activity of these enzymes is essential for the proper assembly of LPS and LOS, which are key components of the outer membrane of Gram-negative bacteria and play a significant role in the bacterial outer membrane's integrity and interaction with the host immune system.
Multi-functional host-pathogen interaction and enzymatic activity protein (Host-pathogen_enzymatic-act)
Type: Family

This family of proteins includes a variety of functions related to host-pathogen interactions, enzymatic activity, and cellular processes. Members are involved in the secretion of factors that may influence host immune responses, such as the maturation and activation of dendritic cells, and the modulation of cytokine production. Some proteins have enzymatic roles, including the oxidation of specific substrates and the biosynthesis of heme components. Others contribute to the stability of cellular transport complexes or facilitate bacterial spread by interacting with host proteins. The family also includes proteins with uncharacterized functions.
Chloroplastic and Bacterial Serine Proteases (Chloro_Bact_Ser_Proteases)
Type: Family

The peptidase S1C family consists of serine proteases that play a role in the degradation of abnormal exported proteins, propeptide processing, and maturation of native proteins. They are involved in stress resistance, including responses to heat shock, ethanol, puromycin, and NaCl, during active exponential growth. Some family members act as regulatory proteases that are conditionally activated by environmental triggers, while others have a chaperone function, assisting in the refolding of misfolded proteins. The family includes proteases with PDZ domains that regulate activity and substrate specificity, such as by binding to peptides ending with C-terminal Tyr-X-Phe sequences. These proteases are implicated in various cellular processes, including the stress response network, virulence, and regulated intramembrane proteolysis cascades.
Peptidase C40 (Peptidase_C40)
Type: Family

The peptidase C40 family comprises enzymes with diverse cell wall remodeling activities. Members of this family are involved in processes such as peptidoglycan binding, cell wall expansion, and cell separation during vegetative growth. Some proteins within this family exhibit endopeptidase activity, cleaving specific peptide bonds within the peptidoglycan layer, which is crucial for bacterial cell wall integrity and dynamics. For instance, some proteins hydrolyze gamma-D-glutamate-meso-diaminopimelic acid bonds, while others target gamma-D-glutamyl-L-lysine linkages. Additionally, certain family members are implicated in the invasion of host cells by Listeria species, suggesting a role in bacterial pathogenicity. The family also includes bifunctional enzymes with both muramidase and DL-endopeptidase activities, contributing to cell wall turnover and conjugation processes. Regulatory mechanisms such as proteolytic processing are observed in some members, indicating a complex control of activity in response to cellular growth phases.
Polysaccharide Synthase-Related Protein (Polysaccharide_Synthase-Rel)
Type: Family

This family of proteins is involved in the biosynthesis and modification of polysaccharides and related molecules. Members of this family exhibit a range of enzymatic activities, including the epimerization of UDP-galactose to UDP-glucose, which is a key step in the production of various polysaccharides. Some proteins within this family are also involved in the biosynthesis of pseudaminic acid, a sialic-acid-like sugar, by possessing both C6 dehydratase and C5 epimerase activities. This process is crucial for the modification of flagellin. Additionally, certain members are implicated in the formation of biofilms and the biosynthesis of capsular polysaccharides, which are important for bacterial virulence and surface structure. The family also includes proteins with uncharacterized functions that may be related to polysaccharide synthesis or modification.
ABC transporter permease/solute-binding domain-containing protein (ABC_transp_perm/SBD)
Type: Family

This family of proteins is involved in the transport of various osmoprotectants and nutrients across cellular membranes. They are part of ABC transporter complexes and are responsible for the translocation of substrates such as ergothioneine, a thiol antioxidant, as well as glycine betaine, carnitine, and choline, which are involved in osmoprotection and cryoprotection. These proteins typically contain fused transmembrane domains and solute-binding domains, which undergo conformational changes upon substrate binding. Some members exhibit specificity for certain substrates, while others can transport multiple types of molecules.
Ubiquinone biosynthesis monooxygenase UbiH/COQ6 (UbiH/COQ6_monooxygenase)
Type: Family

The UbiH/COQ6 family consists of FAD-dependent monooxygenases involved in ubiquinone biosynthesis, a vital component of the mitochondrial electron transport chain. Members of this family are responsible for various hydroxylation reactions on the aromatic ring of ubiquinone precursors, such as the hydroxylation of polyprenylated benzoic acid derivatives. These enzymes may also participate in the deamination of amino derivatives of these precursors. The electrons for these reactions are typically sourced from NADPH and transferred via a ferredoxin and ferredoxin reductase system. The UbiH/COQ6 family plays a crucial role in the biosynthetic pathway of coenzyme Q, affecting cellular respiration and energy production.
N-acetylmuramoyl-L-alanine amidase 2 (NAMLAA_amidase_2)
Type: Family

This family of proteins includes autolysins and amidases that play a crucial role in bacterial cell wall metabolism. They are involved in processes such as cell separation, cell-wall turnover, and peptidoglycan recycling. These enzymes specifically cleave the amide bond between the lactyl group of N-acetylmuramic acid and the alpha-amino group of L-alanine in certain cell wall degradation products. Some members are also implicated in the induction of beta-lactamase and may participate in genetic transformation, flagella formation, sporulation, and bacteriophage-mediated cell lysis. Their activity is known to be inhibited by metal chelators, indicating a dependence on metal ions for function.
Mitochondrial Complex I NDUFA9 Subunit (ComplexI_NDUFA9_subunit)
Type: Family

The NDUFA9 complex I subunit family comprises accessory subunits of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), which are not directly involved in catalysis but are essential for proper assembly and function of Complex I. Complex I plays a crucial role in cellular energy production, transferring electrons from NADH to the respiratory chain with ubiquinone as the immediate electron acceptor. Members of the family are involved in various aspects of the electron transfer process and are essential for efficient mitochondrial function and energy metabolism.
Class-I Fumarase/Tartrate Dehydratase (Class-I_Fumarase/Tartrate_DH)
Type: Family

The Class-I Fumarase Family comprises enzymes that catalyze the reversible hydration of fumarate to (S)-malate, a key step in the tricarboxylic acid (TCA) cycle for energy production in the form of NADH. Members function predominantly as aerobic enzymes, with some displaying D-tartrate dehydratase activity, although they are generally unable to convert (R)-malate, L-tartrate, or meso-tartrate. The family also includes L(+)-tartrate dehydratases, which are involved in tartrate metabolism. Activity of these enzymes can be regulated by various inhibitors, such as 2-thiomalate and 3-hydroxy-2-nitropropionate, and some are sensitive to inactivation by oxygen. The family is characterized by the presence of a catalytic [4Fe-4S] cluster, essential for their enzymatic function.
FAD-binding Monooxygenases Superfamily (FAD-bind_Monooxygenase_sf)
Type: Family

The FAD-binding monooxygenase family comprises enzymes that catalyze a variety of oxidation reactions, often involving the insertion of an oxygen atom into organic substrates. These reactions are crucial in diverse biological processes, including the biosynthesis of polyketides, toxins, and other secondary metabolites. Family members are known to participate in Baeyer-Villiger oxidation reactions, converting ketones to esters or lactones, and may also be involved in hydroxylations and sulfoxidations. The enzymes utilize flavin adenine dinucleotide (FAD) as a cofactor and typically require NADPH or NADH as an electron donor. Their activities contribute to the virulence of pathogens, the production of mycotoxins, and the synthesis of various bioactive compounds.
Ubiquitin ligases and GEF domain-containing protein (Ub_ligase/GEF_domain)
Type: Family

This family of proteins includes E3 ubiquitin-protein ligases and guanine nucleotide exchange factors (GEFs), which are involved in a variety of cellular processes. The E3 ubiquitin-protein ligases in this family are responsible for the ubiquitination of substrates, a post-translational modification that can lead to protein degradation, signal transduction, or other cellular responses. They play roles in DNA damage repair, iron metabolism, and the regulation of signaling pathways such as the insulin-like growth factor receptor pathway. The GEFs in this family are involved in the activation of small GTPases, which are molecular switches that regulate secretion processes. Other members of this family are implicated in UV-B photoreception, mitochondrial function, and the regulation of plant growth and development.
Phosphatidylglycerol lysyltransferase (PG_lysyltransferase)
Type: Family

The LPG synthase family catalyzes the transfer of a lysyl group from L-lysyl-tRNA(Lys) to membrane-bound phosphatidylglycerol (PG), resulting in the formation of lysylphosphatidylglycerol (LPG), which is a major component of the bacterial membrane with a positive net charge. The synthesis of LPG is crucial for bacterial virulence, as it plays a role in the resistance mechanism against cationic antimicrobial peptides (CAMPs) produced by the host's immune system and competing microorganisms. The lysinylation of PG by the LPG synthase family leads to a reduction in the overall negative charge of the bacterial membrane, thereby repelling CAMPs and contributing to the bacteria's defense against these antimicrobial agents.
Type I restriction enzyme S subunit (Type-I_RE_S_subunit)
Type: Family

Type I restriction enzyme specificity subunits (S subunits) are part of a multi-subunit enzyme complex involved in the recognition and modification of DNA. These subunits determine the DNA sequence specificity for the enzyme complex. Together with the modification (M) and restriction (R) subunits, they form a system that can act as a methyltransferase, modifying adenine residues within a specific DNA sequence to protect the host genome from invasion by foreign DNA. If the DNA is unmodified, the complex functions as an endonuclease, cleaving the DNA at a distance from the recognition site. The S subunits contain two DNA recognition domains, each recognizing specific components of the target sequence. The activity of the complex is also dependent on the methylation state of the DNA, with hemimethylated sites being modified rather than cleaved. This system also exhibits ATP-dependent DNA translocation activity, which can lead to DNA cleavage upon collision events.
START domain-containing lipid transfer (START_lipid_transfer)
Type: Family

The START domain-containing protein family is involved in the non-vesicular intracellular trafficking and intermembrane transfer of specific lipids. Members of this family can recognize and shuttle various lipid species, including ceramides, diacylglycerol lipids, phosphatidylcholine, and phosphatidyethanolamine. The START domain is key for lipid recognition and membrane interaction, while the PH domain typically targets the Golgi apparatus. Some proteins within this family also contain an FFAT motif for interaction with VAPA, VAPB, and MOSPD2. Functions of these proteins are diverse, ranging from roles in sperm maturation, fertilization, neural and skeletal muscle development, to the prevention of exaggerated allergic responses and apoptosis regulation. They also may contribute to hepatocellular transport of lipids during bile formation and potentially interact with animal cells in the case of bacterial members.
Glycosyl Hydrolase 32 Enzymes (GH32_Enzymes)
Type: Family

This family of proteins includes enzymes that are primarily involved in the hydrolysis of sucrose and related oligosaccharides. Members of this family are characterized by their ability to cleave the glycosidic bond in sucrose to release fructose and glucose. Some members are also capable of hydrolyzing sucrose-6-phosphate. The enzymatic activity of these proteins allows bacteria to utilize sucrose as a sole carbon source, which is crucial for their metabolism and survival in environments where sucrose is the predominant sugar. Additionally, certain members of this family have been shown to hydrolyze other fructosides such as raffinose, inulin, and levan in a specific manner, further underscoring the importance of these enzymes in carbohydrate metabolism.
Glycyl Radical Enzyme (GRE)
Type: Family

This family of proteins includes enzymes that perform radical-mediated chemical reactions, typically involving the cleavage or formation of carbon-based bonds in various substrates. Members of this family are characterized by the presence of a glycyl radical that is essential for their catalytic activity. The enzymes are involved in diverse metabolic processes, such as the anaerobic degradation of aromatic compounds, fermentation of amino acids, and utilization of organosulfur compounds. They catalyze reactions like the addition of fumarate to toluene, decarboxylation of hydroxyphenylacetates, cleavage of C-S bonds in sulfonates, and dehydration of hydroxyproline. These activities contribute to the catabolism of complex molecules in various environmental and physiological contexts, often providing growth advantages or metabolic benefits to the organisms that harbor them. The enzymes are sensitive to oxygen, which can rapidly inactivate them, highlighting their adaptation to anaerobic conditions.
Teneurin (Teneurin)
Type: Family

Teneurins are a family of phylogenetically conserved transmembrane glycoproteins expressed during pattern formation and morphogenesis . Originally discovered as ten-m and ten-a in Drosophila melanogaster, the teneurin family is conserved from Caenorhabditis elegans (ten-1) to vertebrates, in which four paralogs exist (teneurin-1 to -4 or odz-1 to -4). Their distinct domain architecture is highly conserved between invertebrate and vertebrate teneurins, particularly in the extracellular part. The intracellular domains of Ten-a, Ten-m/Odz and C. elegans Ten-1 are significantly different, both in size and structure, from the comparable domains of vertebrate teneurins, but the extracellular domains of all of these proteins are remarkably similar.

The large C-terminal extracellular domain consists of eight EGF-like repeats (see

), a region of conserved cysteines and unique YD-repeats. The N-terminal intracellular domain of vertebrate teneurins contains two EF-hand-like calcium-binding motifs and two polyproline regions involved in protein-protein interactions, followed by a single-span transmembrane domain. The intracellular domain is linked to the cytoskeleton through its interaction with the adaptor protein CAP/ponsin and can be cleaved near (or possibly in) the transmembrane domain and transported to the nucleus , giving teneurins the potential to act as transcription factors

,

]. There is considerable divergence between intracellular domains of invertebrate and vertebrate teneurins as well as between different invertebrate proteins .

Teneurin proteins are involved in the development and function of the nervous system . They are ancient cell-cell adhesion receptors that play a vital role in establishing precise connectivity within the nervous system, including the formation of topographic projections, dendrite morphogenesis, and axon targeting . These proteins mediate both homophilic and heterophilic cell-cell adhesion, which is essential for synapse assembly and the formation of neural circuits. They also act as ligands for specific receptors, contributing to axon guidance and intracellular signal transduction. Additionally, certain members are implicated in gene transcription regulation, cytoskeleton reorganisation, and neuroplasticity. Teneurins may also contribute to the differentiation of specific cell types, and play roles in stress response and neuroprotection. Their functions are fundamental to neural development and the establishment of proper nervous system connectivity .
Insect Cuticle Structural (Insect_Cuticle_Struc_Prot)
Type: Family

The Cuticle Protein family comprises structural proteins that are integral components of the protective cuticle layer in various insect species. These proteins play a crucial role in determining the physical properties of the cuticle, such as stiffness, elasticity, and resilience, which are essential for insect survival and functions like locomotion and flight. The family is characterized by the presence of tetrapeptide (A-A-P-[AV]) repeats, which are a common feature in the envelope proteins of different species, suggesting a conserved role in cuticle formation and maintenance. The family includes proteins from the cuticle of migratory locusts, African malaria mosquitoes, and the larvae and pupae of other insects, each contributing to the structural integrity of their respective cuticle layers.
Secreted Mono/Diacylglycerol Lipase (Sec_MonoDiacylglyc_Lipase)
Type: Family

The lipase family, part of the AB hydrolase superfamily, encompasses secreted enzymes predominantly involved in the hydrolysis of mono- and diacylglycerols. Members of this family exhibit a strong preference for cleaving ester bonds at the 1,3-positions of glycerides, releasing free fatty acids, particularly oleic acid, and glycerol. These lipases play a crucial role in lipid metabolism, especially for organisms like Malassezia species that lack fatty acid synthase genes and rely on external lipid sources for growth. The family's involvement extends to pathogenicity, as the lipases are implicated in skin conditions such as Dandruff and seborrheic dermatitis by breaking down sebaceous lipids and generating irritants. Some members also have the ability to synthesize diacylglycerols from monoacylglycerols. The activity of these lipases is regulated by metal ions and specific inhibitors, and their activity is maximized at a lipid-water interface, suggesting interfacial activation mechanisms.