SII-SWORD/CoKE huggingface dataset:
Omega-hydroxy-beta-dihydromenaquinone-9 sulfotransferase Stf3 (Stf3_sulfotransferase)
Type: Family

The Stf3 family is involved in the biosynthesis of sulfomenaquinone (SMK), a compound that plays a role in the regulation of virulence in mycobacteria. Members of the Stf3 family are enzymes that catalyze the sulfonation of omega-hydroxy-beta-dihydromenaquinone-9 using 3'-phosphoadenosine-5'-phosphosulfate (PAPS) as the sulfonate donor. The reaction results in the formation of omega-sulfo-beta-dihydromenaquinone-9, also known as sulfomenaquinone. This sulfonated form of menaquinone is localized in the outer envelope of mycobacteria such as Mycobacterium tuberculosis and Mycobacterium bovis, where it contributes to the modulation of the pathogen's virulence, potentially affecting host-pathogen interactions and the bacterial ability to cause disease.
Omega-amidase YafV (Omega-amidase_YafV)
Type: Family

The Omega-amidase YafV family consists of enzymes that play a role in amino acid metabolism and possibly in metabolite repair. Members of this family are characterized by their ability to hydrolyze alpha-ketoglutaramate (a-KGM) to alpha-ketoglutarate (alpha-KG) and ammonia. The enzymes exhibit varying specific activities for this reaction, with some showing weak activity toward L-glutamine. They do not act on glutathione or its derivatives. As part of the carbon-nitrogen hydrolase superfamily, specifically the NIT1/NIT2 family, the Omega-amidase YafV proteins may be involved in the detoxification of harmful metabolic by-products, thereby maintaining cellular homeostasis.
ABC transporter tungstate-binding (ABC-Tungstate_binding)
Type: Family

This family of proteins is involved in the transport of anions, particularly tungstate, across cellular membranes. They are components of ABC transporter complexes, which are known for their role in high-affinity uptake systems. Members of this family exhibit specificity for tungstate and are essential for its uptake, indicating a specialized role in tungstate homeostasis and metabolism.
Fatty-acid amide hydrolase 2 (FAAH2)
Type: Family

This family of proteins is involved in the metabolic regulation of endogenous fatty acid amides. Members of this family function as enzymes that catalyze the hydrolysis of fatty amides, including sleep-inducing and signaling lipids such as oleamide and anandamide, into their respective fatty acids. This hydrolytic activity modulates the signaling functions of these molecules, which play roles in various physiological processes. The enzymes show substrate specificity, with a preference for monounsaturated substrates over polyunsaturated ones. They are subject to inhibition by certain chemical compounds, which can affect their regulatory role in lipid signaling pathways.
Carbohydrate Esterase 4 (CE4)
Type: Family

This family of proteins is involved in the modification of chitin, a long-chain polymer of N-acetylglucosamine, which is a component of the cell wall in fungi, the exoskeletons of arthropods, and the radulae of mollusks. Members of this family function as chitin deacetylases, enzymes that catalyze the removal of acetyl groups from N-acetyl-D-glucosamine residues within chitin. This deacetylation process is crucial for the remodeling of chitin and affects its solubility and structural properties. The activity of these enzymes is essential for the proper function of chitin in various biological contexts, including structural support and protection. Some members require specific protein interactions for their enzymatic activity, indicating a level of regulation and specificity in their function.
Mitochondrial Hydroxyacyl-thioester Dehydratase (Mitochondrial_HTD2)
Type: Family

The HTD2 family comprises mitochondrial enzymes involved in fatty acid biosynthesis and the glyoxylate assimilation cycle. Members of the HTD2 family, such as Hydroxyacyl-thioester dehydratase type 2, play a crucial role in respiratory growth and maintaining normal mitochondrial morphology by catalyzing the dehydration of 3-hydroxyacyl-thioesters. Another member, Mesaconyl-C(4)-CoA hydratase, is essential for converting mesaconyl-C4-CoA to (3S)-citramalyl-CoA, a step in the glyoxylate assimilation cycle that helps regenerate acetyl-CoA and produce pyruvate for biosynthesis. The activity of these enzymes can be regulated by substrate concentration, as seen with mesaconyl-C(4)-CoA hydratase, which is inhibited by high levels of its substrate.
Mitochondrial N-acetyltransferase (Mito_N-acetyltransferase)
Type: Family

This family of proteins includes N-acetyltransferases involved in the cellular response to oxidative stress. Members of this family are known to acetylate intermediates in proline metabolism, specifically the (S)-1-pyrroline-5-carboxylate (P5C) or its tautomer glutamate-5-semialdehyde (GSA), which are implicated in arginine biosynthesis within mitochondria. The acetylation process is believed to reduce the levels of reactive oxygen species (ROS) generated by these intermediates, thereby protecting the cell from oxidative damage. Some members also have the ability to acetylate and detoxify azetidine-2-carboxylate (AZC), a proline analog, although this is not considered a natural substrate in yeast.
Fungal Glutaminase GtaA (Glutaminase_GtaA)
Type: Family

This family of proteins includes enzymes that catalyze the hydrolysis of glutamine to glutamic acid, a reaction that is central to nitrogen metabolism. Members of this family are capable of processing both L-glutamine and D-glutamine. The enzymatic activity of these proteins is crucial for the production of glutamic acid, which is a key amino acid in various metabolic pathways. The activity of these enzymes can be modulated by environmental factors, as exemplified by the inhibition of activity in high-salinity conditions such as the presence of sodium chloride.
Glycerol-3-phosphate O-acyltransferase (GPAT/DAPAT)
Type: Family

This family of proteins includes enzymes with acyltransferase activity, specifically functioning as glycerol-3-phosphate O-acyltransferases. They catalyze the initial step in the biosynthesis of glycerophospholipids and triacylglycerols, transferring a fatty acid from fatty acyl-CoA to the sn-1 position of glycerol-3-phosphate, resulting in the formation of lysophosphatidic acid. Members of this family exhibit substrate specificity, with some preferring glycerol-3-phosphate over dihydroxyacetone phosphate and showing selectivity for certain fatty acyl chain lengths. These enzymes play a crucial role in lipid metabolism and are involved in the regulation of fatty acid desaturation and the balance of saturated and unsaturated fatty acids within the cell. They also contribute to the synthesis of diacylglycerols and phosphatidylcholine, which are key components in cell signaling and membrane structure.
Glycerol 3-phosphate Oxidase/Oxidoreductase (G3P_Oxidase/Oxidoreductase)
Type: Family

This family of proteins includes enzymes that are involved in the metabolism of glycerol. They catalyze the oxidation of glycerol 3-phosphate (G3P) to dihydroxyacetone phosphate (DHAP), a key step in glycerol utilization and energy production. Some members of this family are also capable of oxidizing glyceraldehyde 3-phosphate (GAP) to an unknown product, potentially contributing to hydrogen peroxide (H2O2) production during infection. The enzymes are characterized by their ability to reduce oxygen to hydrogen peroxide in the process, which is significant for the cytotoxic effects of certain pathogens on host cells. They do not exhibit dehydrogenase activity with NAD(+) as a cofactor, and while some may show oxidase activity with other electron acceptors, this is not considered their primary physiological function.
MlaB ABC Transporter Complex Protein (MlaB_ABC_Transporter)
Type: Family

This family of proteins is involved in an ABC transporter complex known as MlaFEDB, which plays a crucial role in maintaining lipid asymmetry in the outer membrane of certain bacteria. These proteins are responsible for the retrograde trafficking of phospholipids from the outer membrane back to the inner membrane, a process essential for the proper function and integrity of the bacterial cell envelope. Members of this family, specifically the MlaB proteins, are key to both the assembly and the operational activity of the MlaFEDB complex. They may influence the structure and stability of MlaF, thereby modulating the transporter's function.
Type II TA system RelE toxin (TA_system_RelE_toxin)
Type: Family

This family of proteins includes toxic components of type II toxin-antitoxin (TA) systems. They exhibit ribonuclease activity and are involved in the regulation of cellular processes through their interaction with cognate antitoxins. These proteins are typically encoded by operons that also encode their respective antitoxins, forming a stable complex that neutralizes the toxin's activity. Disruption of this complex can lead to the toxin's activation, which may result in growth arrest or cell death. The antitoxin components also regulate the expression of the toxin gene, ensuring the toxin is only active under certain conditions.
Integrated Stress Response Activator (ISR_Activator)
Type: Family

This family of proteins acts as activators of the integrated stress response (ISR), particularly in response to iron deficiency and mitochondrial stress. Members of this family detect impaired protein import into mitochondria, leading to their localization at the mitochondrial surface. There, they bind to and activate EIF2AK1/HRI, a protein kinase. This activation results in the phosphorylation of eIF-2-alpha, reducing global protein synthesis and promoting the expression of specific genes, including ATF4, a key regulator of the ISR. Additionally, these proteins may play a role in death receptor-mediated apoptosis by influencing caspase activation.
Alpha-tectorin (Alpha-tectorin)
Type: Family

Alpha-tectorins are major non-collagenous components of the tectorial membrane, an extracellular matrix in the inner ear. The tectorial membrane overlays the neuroepithelium of the cochlea and makes contact with the stereocilia of sensory hair cells. Alpha-tectorins play a crucial role in hearing by facilitating the movement of hair cells in response to sound, which in turn deflects the stereocilia and converts sound waves into electrical signals within the hair cells. The presence of a zona pellucida domain suggests that alpha-tectorins may also be involved in filament formation, contributing to the structural integrity of the tectorial membrane.
Glycosyl Hydrolase 18 Chitinase (GH18_Chitinase)
Type: Family

This family of proteins includes enzymes with chitinase activity, which are involved in the degradation of chitin. Chitin is a major component of fungal cell walls and the exoskeletons of arthropods and other animals. Members of this family play a role in various biological processes, including the breakdown of chitin for nutrient acquisition and defense mechanisms against chitin-containing pathogens. Some proteins in this family exhibit bifunctional activity, combining chitinase with lysozyme functions, which further contributes to their role in antimicrobial defense by breaking down bacterial cell walls. These proteins are classified within the glycosyl hydrolase 18 family and are further subdivided into different subfamilies based on sequence similarity and functional characteristics.
Plant MAP kinase kinase kinase (Plant_MAPKKK)
Type: Family

This family of proteins includes mitogen-activated protein kinase kinase kinases (MAPKKKs) that are integral components of the abscisic acid (ABA) signaling pathway, particularly in response to abiotic stresses. They are involved in the activation of downstream MAP kinases, such as MPK1, MPK2, MPK6, MPK7, and MPK14, through phosphorylation. These proteins play a role in various plant physiological processes including stomatal development and movement, root growth, leaf senescence, and the regulation of gene expression related to stress responses. Their kinase activity is modulated by ABA, phosphorylation, and interactions with other proteins such as ABI1 and SRK2E.
NACHT and WD repeat domain-containing protein (NACHT-WD_repeat)
Type: Family

This family of proteins includes members that contain NACHT and WD repeat domains. The NACHT domain is typically involved in nucleotide binding and signal transduction, often playing a role in the regulation of inflammatory and immune responses. The WD repeat domain is known for mediating protein-protein interactions, which can be crucial in various cellular processes such as signal transduction, cell cycle control, and apoptosis. One member from Caenorhabditis elegans has been studied for its role in sensory neurons, where it is involved in the avoidance response to noxious chemicals and in promoting dauer formation in response to specific pheromones. This suggests that the family may be involved in sensory perception and stress response mechanisms.
Rubrerythrin-2/Nigerythrin (Rbr2/Nigerythrin)
Type: Family

This protein family is involved in peroxidase activity, specifically utilizing NADH as an electron donor to reduce hydrogen peroxide (H2O2). Members of the family, such as Nigerythrin and Rubrerythrin-2, function in oxidative stress response by catalysing the conversion of H2O2 into water, thereby protecting the cell from oxidative damage . Rubrerythrin-2 acts as the terminal component of an NADH peroxidase system, with NADH:rubredoxin oxidoreductase (NROR) serving as an electron transport intermediary . Rubredoxin enhances the efficiency of this electron transfer process. Although the exact biological role of the uncharacterised protein in the family remains unclear, the known functions of other members suggest a general role in cellular redox homeostasis.

Also included in this family is symerythrin (

), a rubrerythrin variant from the oxygenic phototroph Cyanophora paradoxa . A particularity of this protein is its high internal symmetry, which supports the notion that its core four-helix bundle was formed by the gene duplication and fusion of a two-helix peptide .
NTPase KAP P-loop domain-containing protein (NTPase_KAP_P-loop)
Type: Family

This family of proteins includes members that are involved in nucleotide triphosphate (NTP) hydrolysis, which is a common molecular function that provides energy for various cellular processes. Additionally, some members of this family are associated with bacterial immunity, specifically the inhibition of bacteriophage infection. This suggests a functional diversity within the family, with some members potentially participating in cellular energy metabolism or signaling, while others may play a role in defense mechanisms against viral infection.
Lysozyme Inhibitor LprI (Lysozyme_Inhibitor_LprI)
Type: Family

This family of proteins is characterized by a strong affinity for lysozyme, which they bind and inhibit. This interaction is thought to be a defensive mechanism, allowing bacteria to evade the antimicrobial effects of lysozyme, an enzyme commonly found in host cells. The proteins are implicated in enhancing bacterial survival within lysozyme-producing cells, such as macrophages. The presence of these proteins in bacteria like Mycobacterium tuberculosis and Mycobacterium smegmatis is associated with increased resistance to lysozyme and improved survival during intracellular infections. The proteins are part of an operon that includes another protein, which may also contribute to the survival of the bacteria in human cell lines.
Terminal-alkyne amino-acid exporter (Alkyne_AA_exporter)
Type: Family

This family of proteins includes transporters that are part of the EamA transporter family. Members of this family are likely to be involved in the export of specific amino acids that have terminal alkyne groups, which may have antibiotic properties. These amino acids include L-propargylglycine and L-beta-ethynylserine. The proteins may play a role in the resistance mechanism of the producing organisms by exporting these antibiotic compounds, thus preventing self-toxicity. The function of some members within this family remains uncharacterized, suggesting potential diversity in substrate specificity or transport mechanisms.
Bacterial ribosomal protein S1 (Ribosomal_protein_S1)
Type: Family

This family of proteins is involved in the initial stages of protein synthesis by binding to messenger RNA (mRNA) and playing a role in the assembly of the small ribosomal subunit. These proteins are essential for the translation process, ensuring the proper alignment of mRNA and ribosomes for efficient decoding of genetic information into proteins.
Steroid receptor co-chaperone (SRC_co-chaperone)
Type: Family

This family of proteins functions as co-chaperones that regulate the activity of the molecular chaperones HSP70 and HSP90. They are involved in the folding process of steroid receptors, including glucocorticoid and progesterone receptors. These proteins are suggested to have a role in recycling chaperone substrates back to the initial stages of the folding pathway if additional folding is necessary. They have the ability to induce the dissociation of HSP90 from chaperone-substrate complexes in an ATP-independent manner, while not affecting HSP70-bound complexes. Additionally, they are involved in the cytoplasmic recruitment of nuclear receptors such as NR1I3.
Extracellular Metalloprotease M4 (Metalloprotease_M4)
Type: Family

This family of proteins includes extracellular metalloproteases that are characterized by their ability to interact with and degrade peptide substrates. Members of this family are involved in various biological processes, including the modulation of antibacterial peptide activity. One known function is the inhibition of insect antibacterial peptides, which can lead to a reduction in the antibacterial activity of certain hemolymph components and cecropins. These metalloproteases are sensitive to specific inhibitors, indicating a regulatory mechanism for their proteolytic activity. The family is part of the broader peptidase M4 family, which is known for its metalloprotease activity.
Mitochondrial malonyltransferase (Mitochondrial_malonyltrans)
Type: Family

This family of proteins catalyzes the transfer of malonyl groups from malonyl-CoA to the phosphopantetheine arm of acyl carrier proteins within mitochondria, indicating a role in mitochondrial fatty acid biosynthesis. Members of this family share a common function in the elongation step of fatty acid synthesis, which is essential for producing the fatty acid components of lipids in eukaryotic cells.
Fungal Detoxification and Toxin Biosynthesis TFs (Fungal_Detox/Toxin_TFs)
Type: Family

The protein family includes transcription factors involved in the regulation of gene clusters responsible for the detoxification and degradation of specific compounds, as well as the biosynthesis of fungal toxins. One member regulates the Fusarium detoxification of benzoxazolinone cluster, contributing to the tolerance against benzoxazolinones like MBOA and BOA, which are degradation products of plant-derived benzoxazinones such as DIMBOA and DIBOA. Another member is implicated in the biosynthesis of cyclopiazonic acid, a potent inhibitor of Ca(2+)-ATPase with a pentacyclic indole tetramic acid structure. These transcription factors are key to the adaptation and survival of fungi in various ecological niches, by enabling them to counteract plant defenses and produce secondary metabolites.
Plant cell wall deacetylase/carbohydrate esterase (PCW_deacetylase/CE)
Type: Family

This family of proteins is involved in the degradation of plant cell wall polysaccharides. Members exhibit esterase activity, catalyzing the deacetylation of acetylated plant polysaccharides such as birchwood xylan and glucomannan. Some family members also display endoglucanase activity against substrates like carboxymethyl cellulose and barley beta-glucan. Additionally, certain proteins within this family can potentiate cellulase activity through non-catalytic cellulose binding. The family includes multifunctional enzymes that may contain distinct modules for cellulase and esterase activities, as well as dockerin modules for integration into cellulosomes, which are multi-enzyme complexes for cellulose degradation.
DnaJ Homolog Subfamily C Member 4 (DnaJ_C4)
Type: Family

The DnaJ homolog subfamily C member 4 family is implicated in cellular processes that may be crucial during spermatogenesis and/or within the male genital tract. Members of this family are likely to assist in the folding of nascent polypeptide chains and the refolding of denatured proteins, acting as molecular chaperones. They may also play a role in the assembly of multiprotein complexes.
Glycosyl Hydrolase 20 Enzymes (GH20_Enzymes)
Type: Family

This family of proteins is involved in the hydrolysis of glycosidic bonds, specifically those in mucopolysaccharides and oligosaccharides. Members of this family exhibit enzymatic activity that cleaves specific linkages in substrates such as mucin, a component of the human intestinal tract, and human milk oligosaccharides (HMOs), which are crucial for the growth of certain gut bacteria in breast-fed infants. The enzymes function by breaking down complex carbohydrates into simpler sugars, playing a significant role in the digestive process and the utilization of nutrients. They display varying substrate specificities and are subject to regulation by different metal ions, with some members being inhibited by ions such as Mn(2+) and Ca(2+), while others are unaffected by Na(+), K(+), and Mg(2+) ions.
Phosphoglycerate Mutase-Related (PGM-Related)
Type: Family

This family of proteins includes enzymes that are related to the phosphoglycerate mutase (PGM) family, which are traditionally known to be involved in glycolysis and gluconeogenesis by catalyzing the interconversion of 3-phosphoglycerate and 2-phosphoglycerate. Members of this family may not all exhibit PGM enzymatic activity but are suggested to play roles in carbohydrate metabolism. Additionally, some proteins in this family may have functions unrelated to PGM activity, such as involvement in the transport of sterols between cellular membranes.
Secondary metabolite-associated S41A peptidase (S41A_metabolite_peptidase)
Type: Family

This family of proteins includes serine peptidases belonging to the S41A subfamily. They play a crucial role in the biosynthesis of various secondary metabolites, such as hexapeptide mycotoxins and antimitotic tetrapeptides. These enzymes are involved in the proteolytic processing of precursor peptides, which is a key step in the production of bioactive compounds. The processed peptides undergo cyclization and a series of post-translational modifications (PTMs) catalyzed by other enzymes within the gene cluster. These modifications include hydroxylations, chlorinations, and methylations, leading to the formation of complex structures with specific biological activities. The precise sequence and timing of these PTMs are not fully understood, but they are essential for the bioactivity of the final products, which have significant implications for plant pathology and agriculture.
Bacterial community development regulator (Bact_com_dev_regulator)
Type: Family

This family of proteins includes members that are implicated in bacterial community development and regulatory processes. Some proteins in this family are thought to interact with other proteins to modulate community dynamics, possibly by influencing cellular differentiation or communication. Specifically, certain members are associated with the regulation of sporulation and competence in bacteria, suggesting a role in the transition between different stages of the bacterial life cycle. These proteins may exert their effects by affecting the translation, stability, or activity of key regulatory molecules, thereby influencing the bacterial response to environmental cues and the coordination of developmental processes.