SII-SWORD/CoKE huggingface dataset:
Gfo/Idh/MocA Oxidoreductases (Gfo/Idh/MocA_Oxidoreductases)
Type: Family

This family of proteins includes enzymes that are involved in various oxidation-reduction (redox) reactions, which are critical for cellular metabolism. Members of this family are characterized by their ability to catalyze the transfer of electrons from one molecule to another, often using NADH or NADPH as cofactors. Functions attributed to this family range from the degradation of plant cell wall components and the reduction of biliverdin to bilirubin, to the specific oxidation of UDP-GlcNAc and the transformation of 4,5-dihydroxyphthalate. Some members are also implicated in the degradation of protocatechuate via specific pathways. The enzymes in this family display a variety of substrate specificities and are involved in distinct metabolic pathways, reflecting their diverse roles in cellular physiology.
PhoH2-like (PhoH2-like)
Type: Family

This entry represents PhoH2 from Mycobacterium tuberculosis, the toxic component of a type II toxin-antitoxin (TA) system , and similar sequences from bacteria and some viral species. Members of this family are believed to play a role in the cellular response to phosphate starvation . They may be implicated in the regulation of phosphate uptake systems and could have ATPase activity associated with various cellular processes. The exact functions can vary among different organisms.
Diverse Oxidoreductases (Diverse_Oxidoreductases)
Type: Family

This family of proteins includes various oxidoreductases that catalyze the oxidation of diverse substrates, ranging from small molecules like carbon monoxide and xanthine to more complex organic compounds such as nicotine and caffeine. Members of this family are involved in key enzymatic processes that facilitate the degradation of phenolic compounds, hydroxylation of nicotinate, and metabolism of nitrogen-containing heterocyclic substrates. They play a role in both aerobic and anaerobic pathways, contributing to the utilization of these compounds as carbon and nitrogen sources in various organisms. The proteins typically contain iron-sulfur clusters or flavin adenine dinucleotide (FAD) as cofactors, which are essential for their catalytic activity. Regulation of activity is observed in some family members, with sensitivity to inhibitors like cyanide, selenide, and sulfide.
Metallo-Beta-Lactamase Glyoxalase II (MBL_Glyoxalase_II)
Type: Family

The Glyoxalase II family, part of the metallo-beta-lactamase superfamily, includes proteins involved in the detoxification of methylglyoxal (MG), a cytotoxic byproduct of glycolysis. Members of the family, such as hydroxyacylglutathione hydrolases, catalyze the hydrolysis of (R)-S-lactoylglutathione to (R)-lactate and glutathione, playing a role in cellular defense against oxidative stress. Some proteins within the family may also participate in secondary metabolism, such as the synthesis of antibiotic polyketides. The family's enzymatic activity can be regulated by metal ions, with some isozymes being inhibited by Cu(2+).
RNA and ubiquinone modification enzymes (RNA/ubiquinone_mod_enzymes)
Type: Family

This family of proteins includes enzymes involved in the modification of RNA molecules and ubiquinone biosynthesis. Members are responsible for hydroxylating specific uridine residues in tRNAs, which is a precursor step in the biosynthesis of modified nucleosides such as 5-hydroxyuridine and 5-carboxymethoxyuridine. These modifications are crucial for the stability and function of tRNA molecules. Other family members are implicated in the oxygen-independent pathway of ubiquinone biosynthesis, essential for electron transport and energy production in cells. Additionally, some proteins in this family exhibit collagenase activity, which may contribute to virulence in certain pathogens by degrading collagen. The family also includes proteins that catalyze the hydroxylation of cytidine in 23S rRNA, a modification important for ribosome function.
Bacterial solute-binding protein 3 (Bact_solute-bind_prot3)
Type: Family

The bacterial solute-binding protein 3 family is involved in the transport of various amino acids across the cell membrane, functioning as part of different ABC transporter complexes. Members of the family bind specific amino acids with high affinity, which is critical for their transport into the cell. These proteins are implicated in the uptake of glutamate, aspartate, glutamine, asparagine, and general L-amino acids. They play essential roles in nutrient acquisition, cell adherence, and symbiotic nitrogen fixation. The binding of their respective ligands can induce conformational changes that may increase the protein's thermal stability, suggesting a regulatory mechanism for transport activity.
2-oxoacid:ferredoxin oxidoreductase (2-oxoacid:Fd_oxidoreductase)
Type: Family

This family of proteins includes enzymes that catalyze the coenzyme A-dependent oxidative decarboxylation of various 2-oxoacids, such as pyruvate, 2-oxobutyrate, glyoxylate, and 2-oxoglutarate, to form their corresponding CoA derivatives. These reactions are crucial in metabolic pathways, including the tricarboxylic acid cycle and alternative metabolic routes. The enzymes are characterized by their interaction with ferredoxin or other electron acceptors and are involved in key energy-producing processes within the cell. One member is specifically noted to participate in an alternative TCA pathway, important for the metabolism of lipids such as fatty acids and cholesterol, particularly in the context of M.tuberculosis infection.
Cytosolic and Metallo Dipeptidase (Cyt/Met_Dipeptidase)
Type: Family

The peptidase M20 family is involved in the hydrolysis of dipeptides, with specific members displaying tissue-specific catabolism of threonyl dipeptides and high activity toward cysteinylglycine, an intermediate in glutathione metabolism. Some members are involved in the degradation of glutathione and other gamma-glu-X bond-containing peptides, playing roles in cell cycle arrest and apoptosis. Others specialize in the hydrolysis of Xaa-His dipeptides, such as carnosine and anserine. Additionally, one member contributes to body odor formation by hydrolyzing Cys-Gly-S-conjugates. Activity can be regulated by inhibitors like bestatin and metal ions, and some members are part of the GSH degradosomal complex.
Cytochrome c-type Dehydrogenase (Cytochrome_c-type_DH)
Type: Family

The Cytochrome c-type Dehydrogenase family comprises enzymes that are involved in various electron transfer processes. Members of this family function as integral components of multicomponent enzyme systems, catalyzing the oxidation of substrates such as ethanol, thiosulfate, and D-gluconate, and transferring electrons to electron acceptors like ubiquinone, tetrathionate, and others embedded in the membrane phospholipids. These proteins contain heme c groups that play a crucial role in the electron transfer chain. Some members are involved in the ethanol oxidase respiratory chain, producing acetic acid from ethanol oxidation, while others participate in the oxidation of thiosulfate to tetrathionate or D-gluconate to 2-dehydro-D-gluconate. Additionally, certain cytochrome c-type proteins function as electron donors in processes such as aerobic respiration and oxygenic photosynthesis.
Heterodisulfide reductase iron-sulfur subunit C (HdrC_iron-sulfur_subunit)
Type: Family

This family of proteins is involved in the reversible reduction of heterodisulfide compounds, specifically CoM-S-S-CoB, to their respective thiol-coenzymes H-S-CoM (coenzyme M) and H-S-CoB (coenzyme B). Members of this family participate in electron transfer processes, which are crucial in methanogenic pathways, including the transfer of electrons from reduced ferredoxin or coenzyme F420 to CoM-S-S-CoB. Some proteins within this family are also implicated in electron bifurcation mechanisms, which contribute to energy conservation in certain methanogens by simultaneously reducing ferredoxin and CoB-CoM heterodisulfide. Additionally, these proteins may be involved in other oxidoreductase activities, including the transfer of electrons to unidentified acceptors or to the menaquinone pool in the membrane during syntrophic growth.
UPF0750 membrane-associated protein (UPF0750_membrane)
Type: Family

This family of proteins includes membrane-associated proteins that are largely uncharacterized. They are identified by their sequence similarity and are grouped based on shared features that suggest a common evolutionary origin. The proteins in this family are found in various bacterial species and are predicted to have roles in cellular processes, possibly related to membrane function or transport. However, the specific biological functions and molecular mechanisms of these proteins remain to be elucidated through experimental studies.
CBS domain-containing protein (CBS_domain-containing)
Type: Family

This family of proteins includes members with diverse biological functions, primarily characterized by the presence of a CBS domain. The CBS domain is known to play a role in various cellular processes through its involvement in the regulation of enzyme activity and protein conformation. Proteins in this family are involved in metabolic pathways, such as homocysteine biosynthesis, and may function as transcriptional repressors, regulating gene expression. Some members are implicated in meiosis, while others are uncharacterized, suggesting a broad range of potential functions within the family. The presence of CBS domains suggests a common mechanism of ligand-induced conformational changes, which may be a key regulatory feature across the family.
Peptidase U62 metalloprotease (Peptidase_U62_metallo)
Type: Family

This family of proteins includes metalloproteases that are characterized by a conserved motif which likely serves as their active site. Members of this family are involved in various biological processes, including the degradation of specific substrates such as azocasein and the bacterial CcdA protein. Some proteins in this family have been described to suppress the activity of the carbon storage regulator CsrA, indicating a role in the regulation of carbon storage and metabolism. The metalloprotease activity suggests that these proteins require a metal ion, such as zinc, for their catalytic function, which is consistent with the presence of a conserved motif indicative of metal binding and catalysis.
Peptidase M42 aminopeptidase (Peptidase_M42_aminopept)
Type: Family

The peptidase M42 family comprises enzymes with aminopeptidase activity, which progressively cleave amino acids from the N-terminus of peptide substrates. Members of this family exhibit broad specificity, hydrolyzing di-, tri-, and tetrapeptides with various N-terminal amino acids, although some show preference for specific residues such as lysine or leucine. The activity of these enzymes is generally halted by the presence of a proline residue just before the cleavage site. They do not possess carboxypeptidase, endoproteolytic, or N-terminal deblocking activities. These enzymes are involved in protein degradation, processing oligopeptides into single amino acids. The peptidase M42 family plays a crucial role in cellular protein turnover and metabolism.
Cell Envelope Structural Component (Cell_Envelope_Struct_Comp)
Type: Family

This family of proteins includes components that are involved in the structural organization and integrity of the cell envelope. They typically exhibit a tripartite organization with a C-terminal outer membrane beta-barrel domain, a central trimeric coiled coil, and an N-terminal domain that can interact with the peptidoglycan layer. Some members function as anchoring proteins that bind cellulosomes to the cell surface, while others form a paracrystalline mono-layered assembly known as the S-layer, which coats the surface of bacteria. The S-layer proteins play roles in protecting the cell, potentially acting as nonselective channels that facilitate the exchange of substances with the environment. Additionally, some proteins within this family may be involved in linking the outer membrane to the inner membrane or the peptidoglycan layer, contributing to the cell's structural stability.
D-amino acid metabolism enzyme (D-amino_acid_metab_enzyme)
Type: Family

This family of proteins includes enzymes that are involved in the metabolism of various D-amino acids, primarily D-serine, D-threonine, and D-hydroxyaspartate. Members of this family catalyze reactions such as the deamination of D-serine to produce pyruvate and ammonia, which may play a role in detoxification. Some enzymes also exhibit dehydratase activity towards other D-amino acids, contributing to amino acid catabolism. Additionally, certain family members can catalyze aldolase reactions, participating in the assimilation of glyoxylate through specific metabolic cycles. The enzymes are subject to regulation by various inhibitors, including hydroxylamine, EDTA, and heavy metal ions, reflecting the importance of their precise control within cellular metabolism.
Fungal Secondary Metabolite SDRs (Fungal_SecMetab_SDRs)
Type: Family

The Short-chain dehydrogenases/reductases (SDR) family comprises enzymes involved in various biosynthetic pathways for the production of secondary metabolites, including toxins, pigments, and pharmaceutical compounds. Members of the family function as oxidoreductases, catalyzing reactions such as reductions of ketones to alcohols, dehydrations, and stereo-specific reductions. They play roles in the biosynthesis of compounds like pyriculol, pyriculariol, aflatoxins, sterigmatocystin, dothistromin, griseofulvin, and sordarial. These enzymes are characterized by their ability to mediate complex reactions, including ring closures, halogenations, and epoxidations, contributing to the structural diversity of natural products. The SDR family is essential for the formation of bioactive molecules with applications in agriculture, medicine, and industry.
Flagellar motor switch protein FliN/MopA/SpaO (FliN/MopA/SpaO)
Type: Family

The FliN/MopA/SpaO family comprises proteins that are integral components of the flagellar motor switch complex, also known as the C ring, which is essential for bacterial motility. Members of this family, including FliN, are involved in forming the complex at the base of the basal body. The switch complex is responsible for interacting with chemotaxis proteins such as CheY and CheZ, and it plays a crucial role in determining the direction of flagellar rotation. This interaction is a key part of the bacterial chemotaxis system, allowing bacteria to navigate their environment by moving toward favorable conditions and away from harmful ones.
Thiol:disulfide interchange protein (Thiol:disulfide_interchange)
Type: Family

This family of proteins is involved in the formation and rearrangement of disulfide bonds in periplasmic proteins, which is crucial for their proper folding and stability. Members of this family function by transferring disulfide bonds to substrate proteins, thereby becoming reduced in the process. They are subsequently reoxidized by other proteins, which may include yet uncharacterized partners. Some family members also exhibit disulfide isomerase activity, which helps to correct non-native disulfide bonds in misfolded proteins. Additionally, certain proteins within this family have been noted to possess chaperone activity, assisting in the correct folding of proteins beyond their redox functions.
Bacterial PTS system sugar-specific components (Bacterial_PTS_sugar_comp)
Type: Family

The protein family is involved in the phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS), a key carbohydrate active transport system in bacteria. Members of the family catalyze the phosphorylation of sugar substrates while translocating them across the cell membrane. Specific components of the system, such as EIIB and EIIA, are phosphorylated by phospho-EIIA or phospho-HPr on histidyl or cysteinyl residues, depending on the sugar type. The phosphoryl group is then transferred to the sugar substrate during uptake by the EIIC domain. The family includes components specific for different sugars, such as mannose, fructose, N-acetylgalactosamine, and L-sorbose, indicating a broad specificity for carbohydrate transport and phosphorylation. Some members also play roles in bacterial chemotaxis and phage infection.
Type III Secretion System Stator and Flagellar Assembly (T3SS_Stator/FliH)
Type: Family

The SctL stator family and FliH family proteins are involved in distinct bacterial systems with roles in motility and interaction with host cells. The SctL stator family proteins are components of the type III secretion system (T3SS), also known as the injectisome. They are responsible for injecting bacterial effector proteins into eukaryotic host cells and regulating the activity of the T3SS ATPase. The FliH family proteins are implicated in the assembly and regrowth of bacterial flagella, which are essential for motility. Despite the different systems, both families share a common theme of contributing to the dynamic processes that are crucial for bacterial survival and pathogenicity.
Pyranose 2-oxidase-like (P2Ox-like)
Type: Family

This family includes a group of GMC oxidoreductases, including Pyranose 2-oxidase from Trametes hirsuta (White-rot fungus), a diagnostic marker of diabetes mellitus. Members of this entry catalyse the oxidation of various sugars and related compounds. Some members play crucial roles in metabolic processes such as lignin degradation in wood rot fungi, where they generate hydrogen peroxide as a cosubstrate for ligninolytic peroxidases . The family is characterised by the presence of a flavin adenine dinucleotide (FAD) cofactor and is inhibited by compounds such as HgCl2.
Anti-sigma-K/W factor (Anti-sigma-K/W_factor)
Type: Family

The anti-sigma-K factor family includes proteins that regulate the activity of extracytoplasmic function (ECF) sigma factors such as SigK by maintaining them in an inactive state. These anti-sigma factors bind to their respective sigma factors and prevent them from initiating transcription. The inactivation is reversed through a process known as regulated intramembrane proteolysis (RIP), which is triggered by extracytoplasmic signals. This proteolytic cascade involves sequential cleavage by site-1 protease (S1P) and site-2 protease (S2P, Rip1), followed by further degradation by cytoplasmic proteases, ultimately releasing the sigma factor to activate gene expression. Some members of the family may be dysfunctional due to genetic polymorphisms, leading to altered regulation of sigma factor-dependent genes. The family also includes proteins like RsiW, which belong to the zinc-associated anti-sigma factor (ZAS) superfamily and regulate sigma factors such as SigW.
Diverse Ion Transporter (Diverse_Ion_Transporter)
Type: Family

This family of proteins includes transporters involved in diverse biological processes such as biomineralization, melanogenesis, and possibly ion transport and pH regulation in various cellular compartments. Some members are implicated in the formation of magnetosomes, which are intracellular organelles in magnetotactic bacteria, playing a role in pH regulation within these structures. Other members contribute to melanosome function in mammals, specifically influencing melanosomal pH to optimize the activity of enzymes involved in melanin synthesis. This activity is crucial for the maturation of melanosomes and affects pigmentation, including skin color variation and eye color determination. The family appears to be functionally diverse, with some members uncharacterized, suggesting a broad range of physiological roles.
Bacterial Response Regulator Aspartate Phosphatase (Bac_ResReg_Asp_Phosphatase)
Type: Family

The Rap family proteins are bacterial response regulators with diverse roles in cellular processes such as sporulation and competence development. Members of the family act as aspartate phosphatases, targeting specific response regulators like Spo0F, thereby modulating sporulation initiation. Some Rap proteins also bind to the transcriptional factor ComA, inhibiting its DNA-binding activity and affecting the development of genetic competence. The family is characterized by a conserved domain architecture, including an N-terminal 3-helix bundle domain and a C-terminal TPR domain, which is involved in substrate and inhibitor interactions. Regulatory activity of Rap proteins is often modulated by specific peptide inhibitors, such as Phr peptides, which induce conformational changes that affect their binding and phosphatase activities.
Plant Cell Wall Expansin (Expansin_CellWall)
Type: Family

The Expansin family proteins are implicated in the modification of plant cell walls. They are thought to facilitate cell growth and wall extension by lubricating the movement of cellulose microfibrils. Additionally, they may help maintain the fluidity of the cell wall, which is crucial during processes like slug cell wall formation. Some family members have been associated with aberrant stalk formation when overexpressed. While most members exhibit these functions, one is noted to unlikely encode a protein with expansin activity. Another member, with low expansin activity, may promote plant root colonization and bind to peptidoglycan and plant cell walls without enzymatic action. A distinct protein within the family serves as a stress protein under hyperthermal conditions, donating substrates for transglutaminase and inhibiting various proteases.
Beta-lactamase-like Antibiotic Biosynthesis/Resistance (Beta-lactamase-like_AB/R)
Type: Family

The Beta-lactamase-like family comprises enzymes with diverse hydrolytic activities, often associated with antibiotic biosynthesis or resistance. Members of the family are involved in the hydrolysis of beta-lactam antibiotics, peptidoglycan remodeling, and the biosynthesis of complex natural products such as squalestatin S1 and strobilurin A. These proteins may participate in the release of polyketide products, contribute to self-resistance mechanisms, and perform key steps in the construction of bioactive compounds with cholesterol-lowering and antifungal properties. The family includes proteins that may function as hydrolases within biosynthetic gene clusters, catalyzing reactions that transform precursors into bioactive molecules with diverse pharmacological activities.
Pyruvate synthase subunit PorB-like (PorB-like)
Type: Family

This family of prokaryotic proteins includes various subunits involved in oxidative decarboxylation reactions that are essential for anaerobic metabolism, including Pyruvate synthase subunit PorB from Pyrococcus furiosus. Members of this group catalyse the conversion of different substrates such as pyruvate, ketoisovalerate, and oxalate into their respective products, often with the concomitant reduction of electron acceptors. These enzymes play a role in energy production and carbon flow in anaerobic conditions, enabling organisms to utilize a range of compounds as energy sources. Some members are also involved in the metabolism of aromatic compounds, contributing to the versatility of microbial metabolic pathways. The activities of these proteins are often dependent on cofactors such as thiamine diphosphate and magnesium ions.
Endocytic & GEF Adapter (Endocytic_GEF_Adapter)
Type: Family

The protein family acts as adapter proteins linking endocytic membrane traffic to the actin assembly machinery and as guanine nucleotide exchange factors (GEFs) for various Rho GTPases, including CDC42, RhoA, and RhoB. They are involved in the formation and maturation of clathrin-coated vesicles and endocytosis of receptors such as EGFR and ITGB1. Some family members regulate synaptic vesicle endocytosis and dendrite formation. They may also participate in signaling pathways like the SAPK/JNK pathway and contribute to the ubiquitination and degradation of EGFR, modulating signaling pathways. Additionally, they interact with multiple proteins through domains like SH3 and DH, influencing cellular processes such as actin nucleation and vesicle trafficking.