SII-SWORD/CoKE huggingface dataset:
Major Facilitator Superfamily Sodium/Anion Cotransporter (MFS_Na/Anion_cotransporter)
Type: Family

The Major Facilitator Superfamily Sodium/Anion Cotransporter family is involved in the transport of various substrates across cellular membranes. Members of this family function as uniporters, symporters, and antiporters, often driven by electrochemical gradients. They play critical roles in transporting L-glutamate, phosphate, chloride, protons, potassium, sodium, and other anions. These transport activities are essential for processes such as synaptic transmission, cellular nutrient uptake, and ion homeostasis. Some members are involved in specialized functions like urate transport in the kidney, vesicular storage of neurotransmitters, and regulation of retinal vessel development. The activity of these transporters can be allosterically regulated by ions such as H+ and Cl-, and they are associated with various physiological functions in different tissues, including the nervous system, kidney, and chloroplasts in plants.
Glyoxalase I/Fosfomycin Resistance Protein Families (GlyoxalaseI/FosfomycinResist)
Type: Family

The glyoxalase I and fosfomycin resistance protein families include enzymes with distinct functions. Glyoxalase I family members are involved in the detoxification of methylglyoxal, a byproduct of glycolysis, through the glyoxalase system. This system plays a crucial role in cellular defense against glycation by reactive dicarbonyl compounds. On the other hand, the fosfomycin resistance protein family, particularly the FosB subfamily, includes metallothiol transferases that confer resistance to the antibiotic fosfomycin. These enzymes catalyze the addition of a thiol group, typically from L-cysteine, to fosfomycin, thereby inactivating the antibiotic and providing a defense mechanism for bacteria against this antimicrobial agent. The extradiol ring-cleavage dioxygenase family members are involved in the catabolism of aromatic compounds, catalyzing the meta-cleavage of dihydroxylated aromatic rings in various substrates, which is a critical step in the biodegradation of environmental pollutants such as biphenyls and naphthalenes.
Endophilin/SH3RF (Endophilin_SH3RF)
Type: Family

The Endophilin/SH3RF protein family is involved in various cellular processes including endocytosis, signal transduction, and apoptosis. Members of this family are characterized by the presence of SH3 domains and often BAR domains, which are implicated in membrane curvature and binding. Endophilins play roles in synaptic vesicle endocytosis, receptor internalization, and actin cytoskeleton interaction. SH3RF proteins possess E3 ubiquitin-protein ligase activity, contributing to ubiquitination and protein turnover, and are involved in the JNK signaling pathway. This family is also associated with the regulation of cell morphology, migration, cytokinesis, and neuronal development.
Archaeal FAD synthase (Archaeal_FAD_synthase)
Type: Family

The archaeal FAD synthase family comprises enzymes that catalyze the transfer of the AMP portion of ATP to flavin mononucleotide (FMN) to produce the essential coenzyme flavin adenine dinucleotide (FAD). This reaction is crucial for various biological processes as FAD is a key molecule in redox reactions, playing a pivotal role in metabolism and energy production. Members of this family are characterized by their ability to utilize ATP as a substrate, although some can also use other nucleotides such as CTP and GTP, resulting in the formation of modified coenzymes. The family is inhibited by the product PPi and does not catalyze the reverse reaction. These enzymes are essential for the proper functioning of archaeal organisms, contributing to their adaptability and survival in diverse environments.
Glycosyl Hydrolase 5 (Cellulase A) (Glycosyl_hydrolase_5)
Type: Family

The glycosyl hydrolase 5 (cellulase A) family encompasses enzymes with a variety of functions related to the hydrolysis and metabolism of cellulosic and other glucan-based polysaccharides. Members of this family are involved in the breakdown of cell wall components such as beta-glucan, a key structural element in fungal and plant cell walls. They exhibit activities such as endoglucanase, beta-glucosidase, and transglycosylase, targeting linkages in cellulose, lichenin, cereal beta-D-glucans, and xyloglucans. These enzymes play crucial roles in processes like cell wall remodeling during growth, sporulation, and thermoresistance of spores, as well as in the degradation of biomass for nutrient acquisition. Some members also participate in the biosynthesis of polysaccharides, contributing to the integrity and plasticity of cell walls. The family includes enzymes that can degrade larger cellooligosaccharides and exhibit specificity for different types of glucan substrates.
Hedgehog Signaling (Hedgehog_Signaling)
Type: Family

The Hedgehog protein family is a group of signaling molecules that play a crucial role in a wide range of developmental processes. Members of this family are involved in the patterning of various tissues and organs during embryonic development. They function as morphogens, substances that dictate the fate of cells based on their concentration gradient. Hedgehog proteins are involved in establishing the anterior-posterior axis in embryonic segments, patterning the neural tube, somites, and limb buds, as well as in the differentiation of photoreceptors and the immune response in the gut. They bind to the Patched receptor, which in turn regulates the activity of Smoothened, leading to the activation of target gene transcription. The autoproteolytic cleavage of Hedgehog precursors and subsequent cholesterol modification are critical for their signaling activity. Additionally, Hedgehog proteins are associated with the regulation of bone growth, spermatogenesis, and maintenance of endothelial integrity.
ABC Transporter, Nickel and Peptide Import (ABC_Ni/Peptide_Import)
Type: Family

The ABC Transporter, Nickel and Peptide Import family comprises ATP-binding proteins involved in the transport of various substrates across cellular membranes using ATP hydrolysis for energy. Members of this family are responsible for the import of nickel ions, oligopeptides, dipeptides, and potentially other divalent metal ions, often as part of larger ABC transporter complexes. These proteins play crucial roles in nutrient uptake, resistance to antimicrobial peptides, sporulation, competence, and virulence. The family includes proteins that may also influence the activity of other transport systems, such as potassium uptake proteins.
LysR-type Transcriptional Regulators (LysR-type_TF)
Type: Family

The LysR-type transcriptional regulator family is characterized by its role in gene expression regulation related to various bacterial functions. Members of the family act as transcriptional activators or repressors. They are involved in diverse biological processes including nodulation in symbiotic relationships, degradation of environmental pollutants such as gamma-hexachlorocyclohexane and pentachlorophenol, and regulation of virulence factors. Some regulators respond to specific inducers like flavonoids, which modulate the expression of genes necessary for nodulation. Others control the expression of operons involved in the metabolism of compounds like naphthalene and salicylate. The family also includes global transcription factors that can activate or repress multiple operons, influencing a range of cellular processes. The common feature among these proteins is their helix-turn-helix (HTH) motif, which facilitates DNA binding and the subsequent regulation of gene expression.
DNA Cytosine-5 Methyltransferase (C5-Methyltransferase)
Type: Family

The C5-methyltransferase family is comprised of enzymes that primarily methylate cytosine residues within specific DNA sequences, playing a crucial role in the regulation of gene expression, maintenance of DNA methylation patterns, and protection of DNA from endonuclease cleavage. Members of this family recognize various DNA motifs, often methylating the cytosine at the 5' position. Some members preferentially methylate hemimethylated DNA, contributing to epigenetic inheritance by preserving methylation patterns during DNA replication and cell division. Others are part of restriction-modification systems, protecting bacterial genomes from phage infections by methylating specific sequences and thereby preventing cleavage by corresponding restriction endonucleases. This family also includes enzymes involved in the defense against phages through systems like DISARM. In plants, these methyltransferases are involved in genomic imprinting, embryogenesis, and seed viability, often targeting CHG and CpG sites for methylation, which is essential for gene silencing and suppression of transposable elements.
Mitochondrial Metabolite Transporter (Mito_Metabolite_Transporter)
Type: Family

This family of proteins is involved in the transport of metabolites across the inner mitochondrial membrane. They function as carriers or antiporters, facilitating the exchange of substances such as inorganic anions, dicarboxylates, and tricarboxylates. Some members are implicated in thermogenic respiration, dissipating the proton gradient to generate heat instead of ATP, a process known as uncoupling. Others are involved in maintaining cellular redox balance, oxidative stress protection, and metabolic processes such as gluconeogenesis, fatty acid metabolism, and nitrogen metabolism. The activity of these proteins is regulated by various factors including pH, fatty acids, purine nucleotides, and reactive oxygen species.
Collagen/C1q domain-containing (Collagen/C1q_domain)
Type: Family

The collagen/C1q domain-containing protein family includes a variety of proteins with roles in structural support, immune response, and regulation of various biological processes. Members of the family are characterized by the presence of a C1q domain, which often mediates calcium-binding and is involved in the formation of organic scaffolds, such as in the inner ear for otoliths or in cartilage for mineralization zones. Some family members are involved in the serum complement system, associating with proenzymes to form the C1 complex, which is activated upon interaction with immune complexes. Others are adipokines, influencing fat metabolism and insulin sensitivity, or serve as carrier proteins for factors involved in coagulation. The family also includes proteins that may regulate vessel assembly, angiogenesis, and tissue remodeling, highlighting a diverse range of functions from structural support to metabolic regulation and immune defense.
Membrane Fusion Protein (MFP) (MFP_Efflux_Pump)
Type: Family

The membrane fusion protein (MFP) family is involved in the transport of various substances across the cell membrane. Members of this family typically form efflux pumps with other protein subunits, such as AaeB, to export compounds out of the cell. This is a mechanism used by bacteria to resist toxic substances, including antibiotics and other antimicrobial agents. Some members are specifically known to contribute to the efflux of p-hydroxybenzoic acid, while others are implicated in resistance to a range of drugs, such as puromycin, acriflavine, and tetraphenylarsonium chloride. Additionally, one member is involved in resistance to the fungal toxin fusaric acid. The activity of these efflux pumps is crucial for bacterial survival in hostile environments, as it helps to prevent the accumulation of toxic compounds inside the cell.
Homeobox NK-like transcription regulators (Homeobox_NK-like)
Type: Family

This family of proteins includes transcription factors that play critical roles in embryonic development and organogenesis. Members are involved in the specification and differentiation of various cell types, particularly within the central nervous system, heart, thyroid, lungs, and pancreas. They are characterized by their ability to bind DNA and regulate the expression of target genes, which influences processes such as neuron development, heart formation, and insulin production. Some proteins within this family act as transcriptional activators, while others function as repressors. They are also implicated in the maintenance of energy homeostasis and may have tumor suppressor functions.
Bacterial 4Fe4S Ferredoxin RnfB Subfamily (4Fe4S_Ferredoxin_RnfB)
Type: Family

The RnfB subfamily is part of a membrane-bound ion-translocating oxidoreductase complex that plays a crucial role in energy conservation and metabolic processes across various bacteria. Members of this family are involved in coupling electron transfer to the translocation of ions across the cell membrane. This action is essential for processes such as maintaining the reduced state of SoxR, a regulator of the oxidative stress response, and facilitating nitrogen fixation in certain species. Some family members also contribute to ATP synthesis during heterotrophic growth and are involved in electron transfer to nitrogenase and other components like methanophenazine and heterodisulfide reductase. The RnfB subfamily is characterized by the presence of a 4Fe4S bacterial-type ferredoxin domain, indicating its role in electron transfer reactions.
Glycosyltransferase 51/Transpeptidase (Glycosyltr_51/Transpeptidase)
Type: Family

The glycosyltransferase 51/transpeptidase family is involved in bacterial cell wall formation. Members of the family catalyze the synthesis of cross-linked peptidoglycan from lipid intermediates. The enzymes typically have a bifunctional structure with a penicillin-insensitive transglycosylase N-terminal domain that forms linear glycan strands and a penicillin-sensitive transpeptidase C-terminal domain responsible for cross-linking peptide subunits. This process is essential for maintaining cell wall integrity and shape. Some family members are monofunctional glycosyltransferases that specialize in glycan chain elongation. The activity of these enzymes can be regulated by environmental pH and inhibited by antibiotics such as moenomycin. The family plays a crucial role in various stages of bacterial growth, including vegetative growth and spore outgrowth.
Global Transcriptional Regulators in Environmental Response (Env_Response_Regulators)
Type: Family

The protein family functions as global transcriptional regulators involved in the response to environmental changes, such as oxygen levels and the presence of alternative electron acceptors. They regulate the expression of genes associated with anaerobic respiration, nitrogen fixation, virulence factors, and carbon catabolite repression. Members of the family can act as activators or repressors and may be regulated by allosteric effectors like cAMP or c-di-GMP. They play a role in adapting to anaerobic growth conditions, controlling virulence in pathogenic bacteria, and managing the utilization of carbon sources. The family includes proteins that respond to signals indicating low oxygen conditions or the presence of specific nutrients, and they can influence a wide range of cellular processes, including energy metabolism, gene expression related to stress responses, and the synthesis of enzymes for various metabolic pathways.
Heme sensor protein HssS/ArlS-like (HssS/ArlS-like)
Type: Family

This protein family is comprised of sensor histidine kinases that are part of two-component regulatory systems, which are prevalent in bacterial signal transduction. This entry includes Heme sensor protein HssS from Staphylococcus haemolyticus, a member of the two-component regulatory system HssS/HssR, which is involved in heme homeostasis and virulence modulation, and Signal transduction histidine-protein kinase ArlS from Staphylococcus aureus, a member of the two-component regulatory system ArlS/ArlR involved in the regulation of adhesion, autolysis, multidrug resistance and virulence . These kinases typically function as membrane-associated sensors that autophosphorylate a histidine residue in response to environmental stimuli. The phosphoryl group is then transferred to a response regulator, which modulates the expression of target genes. The family plays a crucial role in various cellular processes including virulence, stress response, biofilm formation, and intracellular homeostasis.
Phosphocarrier protein HPr (HPr)
Type: Family

The HPr family proteins are general components of the phosphoenolpyruvate-dependent sugar phosphotransferase system (sugar PTS), a major carbohydrate active-transport system. They catalyze the phosphorylation of incoming sugar substrates concomitantly with their translocation across the cell membrane. The phosphoryl group from phosphoenolpyruvate (PEP) is transferred to HPr by enzyme I. Phospho-HPr then transfers it to the PTS EIIA domain. Some family members, when phosphorylated on a specific serine residue, interact with the catabolite control protein A (CcpA), forming a complex that binds to DNA at catabolite response elements, acting as a corepressor in carbon catabolite repression (CCR). This mechanism allows bacteria to coordinate and optimize the utilization of available carbon sources. Phosphorylated HPr also plays a role in inducer exclusion, potentially interacting with non-PTS permeases to inhibit their transport activity.
Bacterial Cytoskeleton RodZ (Bact_Cytoskel_RodZ)
Type: Family

The RodZ family proteins are cytoskeletal elements that play a crucial role in bacterial cell shape determination. They are involved in regulating the length of the cell's long axis, which is essential for maintaining the rod shape characteristic of many bacteria. The RodZ proteins contain a helix-turn-helix motif in their cytoplasmic domain, which is implicated in the formation of spiral structures beneath the cytoplasmic membrane. These spirals are thought to be involved in protein-protein interactions that contribute to the overall structure of the RodZ helix. The C-terminal domain of RodZ proteins is believed to interact with enzymes involved in peptidoglycan synthesis, such as penicillin-binding proteins, which are located in the periplasm. This interaction is likely critical for the proper formation of the cell wall and the determination of cell shape. Some members of the family may also be part of the elongasome, a complex involved in synthesizing the peripheral peptidoglycan layer.
Cyclic nucleotide synthase (Cyclic_nucleotide_synthase)
Type: Family

This family of proteins includes receptor-type guanylate cyclases and adenylate cyclases, which are key enzymes in the production of cyclic nucleotide second messengers. These enzymes catalyze the conversion of GTP to cGMP or ATP to cAMP, respectively. The cGMP synthesized by guanylate cyclases is involved in various physiological processes such as phototransduction, chemotaxis, thermotaxis, and regulation of ion channels and sensory neurons. Some family members possess an inactive protein kinase domain and are involved in the regulation of cellular responses to external stimuli, including light, odorants, and peptide hormones. The adenylate cyclases contribute to the regulation of developmental processes and response to extracellular signals.
Olfactory receptor 51/52/56-like (OR51/52/56-like)
Type: Family

The olfactory receptor family is comprised of G-protein coupled receptors with a primary function as odorant receptors. These receptors detect and bind specific molecules from the environment, initiating a signal transduction pathway that results in the perception of smell. Activation of these receptors typically leads to the elevation of intracellular Ca2, cAMP, and the activation of protein kinases such as PKA and MAPK3/MAPK1. Some members of the family, such as Olfactory receptor 51E2, respond to short-chain fatty acids and L-lactate , influencing physiological processes such as melanocyte function, blood pressure regulation, and cell proliferation and migration, particularly in retinal pigment epithelial cells.
Myosin regulatory light chain (Myosin_RLC)
Type: Family

The Myosin regulatory light chain family plays a crucial role in muscle contraction and cellular motility . Members of this family are involved in the regulation of actomyosin ATPase activity, which is essential for muscle contraction and cell movement. These proteins are known to undergo phosphorylation, which affects their interaction with actin and myosin, thereby modulating contractile activity. In striated muscle, including cardiac and skeletal muscle, they contribute to the regulation of heart development and function, as well as muscle integrity during early development. In non-muscle cells, they are implicated in processes such as cytokinesis, receptor capping, and cell locomotion. Some members are also involved in calcium-dependent binding, which is essential for the calcium sensitivity of muscle contraction. Overall, the myosin regulatory light chain family is integral to the fine-tuning of muscle cell contractile activity and plays a role in various cellular functions that require controlled movement.
Heme-degrading monooxygenase (Heme-degrading_MO)
Type: Family

This family of proteins is involved in the utilization of heme from host organisms by bacterial pathogens. Members of this family catalyze the oxidative degradation of the heme macrocyclic porphyrin ring to different products, including biliverdin and staphylobilin, depending on the species. This process also results in the release of free iron, which is a critical nutrient for the bacteria. The activity of these proteins supports bacterial survival and pathogenesis by providing access to iron, which is often limited within the host environment. Some members of this family are also implicated in the regulation of virulence factors and biofilm formation, contributing to the pathogenicity of the bacteria.
Intermediate filament structural protein (Intermediate_filament)
Type: Family

This family of proteins includes various types of intermediate filaments that play critical roles in cell structure and integrity. They are involved in maintaining the shape and mechanical resilience of cells, especially in muscle and neuronal tissues. In muscle cells, they are essential for the proper structure and function of sarcomeres, contributing to the strength and stability of muscle fibers during contraction. In neurons, they are involved in maintaining neuronal caliber and may cooperate with other proteins to form networks that support the nervous system's architecture. Some family members are also implicated in the stabilization of specific mRNAs and may participate in transcriptional regulation.
FGGY Carbohydrate Kinase (FGGY_Carb_Kinase)
Type: Family

The FGGY kinase family is involved in the phosphorylation of various sugars, which is a critical step in their metabolism. Members of this family catalyze the transfer of a phosphate group from ATP to specific hydroxyl groups on sugar substrates. This modification is essential for the subsequent utilization of these sugars in various metabolic pathways. For instance, some members phosphorylate autoinducer-2 (AI-2) affecting quorum sensing and the regulation of gene expression in bacteria. Others are involved in the metabolism of sugars like D-xylulose, L-rhamnose, and L-fuculose, contributing to the catabolism and utilization of these sugars for energy production and biosynthetic processes. The family includes autoinducer-2 kinases, xylulose kinases, rhamnulokinases, and other uncharacterized sugar kinases, highlighting the diversity of substrates and biological functions within this family.
Geranylgeranyl Reductase (Geranylgeranyl_reductase)
Type: Family

The geranylgeranyl reductase family is involved in the biosynthesis of archaeal membrane lipids and chlorophyll synthesis. Members of this family catalyze the reduction of unsaturated archaeols into saturated archaeols, forming archaetidic acid from digeranylgeranylglycerophospholipids via hydrogenation of isoprenoid chains. Some members reduce geranylgeranyl diphosphate to phytyl diphosphate, providing phytol for tocopherol and chlorophyll synthesis. Others are involved in the reduction of menaquinone in mycobacteria or the hydrogenation of geranylgeraniol during bacteriochlorophyll biosynthesis.