SII-SWORD/CoKE huggingface dataset:
CMP-NeuNAc synthase (CMP-NeuNAc_synthase)
Type: Family

The CMP-NeuNAc synthase family is involved in the biosynthesis of sialic acid derivatives, which are important for a variety of biological functions such as cell adhesion, signaling, and immune recognition. Members of this family catalyze the activation of N-acetylneuraminic acid (NeuNAc) and its derivatives to their corresponding cytidine 5'-monophosphate (CMP) conjugates, which are substrates required for the addition of sialic acid to various biomolecules. Some family members also participate in the biosynthesis of legionaminic acid and pseudaminic acid, sialic acid-like sugars that modify flagellin and potentially play roles in bacterial virulence. The family includes enzymes with specificity for different sialic acid derivatives, highlighting the diversity of sialic acid biology across different organisms.
Monovalent cation:proton antiporter 2 (CPA2_transporter)
Type: Family

The CPA2 transporter family includes proteins that function as cation/H(+) antiporters, exchanging monovalent cations such as Na(+) or K(+) against protons across cellular membranes. These antiporters play crucial roles in maintaining ion homeostasis, pH regulation, and osmoregulation in various organisms. Some family members are specifically involved in processes such as pollen tube guidance, stomatal opening, and chloroplast development. The antiporters exhibit substrate specificity, with certain members preferring potassium over sodium ions, and are essential for proper cellular function and response to environmental stresses.
Asparagine Synthetase (Asn_Synthetase)
Type: Family

The asparagine synthetase family is involved in the biosynthesis of asparagine, a process that is essential for nitrogen assimilation, distribution, and remobilization within organisms. Members of this family catalyze the ATP-dependent conversion of aspartate to asparagine using glutamine as a nitrogen source. Some family members can also use ammonia as a nitrogen source. This reaction is crucial in various biological contexts, including plant nitrogen transport via the phloem and potentially in the remobilization of nitrogen during senescence in flowers. Additionally, related enzymes within this family are involved in the biosynthesis of beta-lactam antibiotics, such as carbapenem, by catalyzing the formation of specific intermediates.
SCF complex F-box component (SCF_F-box_component)
Type: Family

This family of proteins includes components of SCF (SKP1-cullin-F-box) E3 ubiquitin ligase complexes, which are involved in the ubiquitination and subsequent proteasomal degradation of target proteins. These proteins play a crucial role in various plant developmental processes, including the regulation of meristem identity, floral organ identity, and determinacy. They are also implicated in the control of cell proliferation in meristems, the regulation of the plastochron, and the enhancement of culm development and strength. Some family members are involved in the formation of vascular bundle systems, which facilitate carbohydrate translocation to panicles, and may be involved in the response to environmental stress such as ozone exposure.
Carbohydrate Metabolism and Transport Regulator (Carb_Metab_Trans_Reg)
Type: Family

The MAL13/EDS1/RGT1 family includes transcription factors that regulate the expression of genes involved in carbohydrate metabolism and transport, particularly in response to glucose availability. Members of the family function as activators or repressors depending on glucose concentration. They play roles in maltose fermentation, glucose transport, and stress adaptation during non-fermentative growth. Some members are involved in the regulation of genes for respiratory growth, gluconeogenesis, the glyoxylate shunt, and the tricarboxylic acid cycle. Others are implicated in the biosynthesis of secondary metabolites with bioactivities, and in the catabolism of uracil and sucrose. The family is characterized by a regulatory role in maintaining mitochondrial morphology and function, and in tolerance to pH and osmotic stress.
YhaM family exoribonucleases and phosphodiesterases (YhaM_exoribonuc/phosphodiest)
Type: Family

The YhaM family is characterized by proteins that predominantly exhibit 3'-5' exoribonuclease activity, which is crucial for the degradation of RNA molecules from the 3' end towards the 5' end. A member of the family also displays single-stranded DNA 3'-5' exonuclease activity and is implicated in the secondary pathway of 23S rRNA 3' end maturation. Additionally, a unique protein within the family functions as a dihydroneopterin 2',3'-cyclic phosphate phosphodiesterase, hydrolyzing the cyclic phosphate of dihydroneopterin compounds and other phosphodiesters, but not nucleotide triphosphates or cyclic nucleotides. The YhaM family thus encompasses enzymes with critical roles in nucleic acid metabolism, including RNA processing and degradation, as well as specialized phosphodiester hydrolysis.
Zinc Iron Protein (ZIP) Transporter (ZIP_Transporter)
Type: Family

The ZIP transporter family mediates the cellular uptake of divalent metal cations such as zinc, manganese, and iron, which are crucial for tissue homeostasis, metabolism, development, and immunity. These transporters function as energy-dependent symporters, often transporting a divalent metal cation alongside bicarbonate anions. Some family members also transport non-essential metals like cadmium, which is cytotoxic and carcinogenic. The ZIP transporters play roles in processes such as epithelial-to-mesenchymal transition, T-cell receptor signaling, meiotic progression, and the adaptation of cells to endoplasmic reticulum stress. They are also involved in dietary zinc uptake, insulin receptor signaling, gluconeogenesis, and innate immunity. The transport activity of these proteins is regulated by metal availability and can be temperature dependent.
ADP-ribosyltransferase diphtheria toxin-like (ARTD/PARP)
Type: Family

The ARTD/PARP family proteins are key players in DNA repair and cellular stress responses. They catalyze the transfer of ADP-ribose units from NAD+ to target proteins, forming poly-ADP-ribose chains. This post-translational modification is crucial for DNA damage detection and repair, including base excision repair and double-strand break repair. The family includes enzymes that mediate both poly-ADP-ribosylation and mono-ADP-ribosylation, with specificity for various amino acids influenced by interacting factors. Beyond DNA repair, these enzymes are involved in transcription regulation, programmed cell death, membrane repair, adipogenesis, and innate immunity. They also play roles in chromatin structure modulation, transcription elongation regulation, and the cGAS-STING pathway. Some family members are implicated in apoptosis following DNA damage, and others are involved in sleep regulation in response to neuronal DNA damage.
Calcium-Dependent Lectins in Immunity and Development (Ca-Dep_Lectins_ImmuneDev)
Type: Family

The protein family includes calcium-dependent lectins involved in innate immune defense, apoptosis, and embryogenesis. Members bind to specific sugar moieties on microorganisms, activating the complement pathway and contributing to pathogen opsonization. Some recognize high mannose oligosaccharides with terminal alpha-1,2-linked mannose epitopes, while others have affinity for fucose, N-acetylglucosamine, or surfactant phospholipids. Functions extend to cell migration regulation, apoptotic cell DNA binding, and surfactant tension reduction in alveoli, essential for respiration. The family also includes members with roles in skeletal growth, hemostasis modulation, and endocytosis.
Elongation Factors and Glutathione S-transferases (EF-GSTs)
Type: Family

The protein family includes elongation factors and glutathione S-transferases (GSTs). Elongation factors are likely involved in anchoring the eukaryotic elongation factor 1 complex to cellular components and may have a role in transcriptional regulation. The GSTs are involved in various biosynthetic pathways for mycotoxins, diterpenes, and other secondary metabolites, acting as detoxification enzymes that conjugate reduced glutathione to electrophiles. They are also implicated in oxidative stress response. Some GSTs are part of gene clusters responsible for the biosynthesis of compounds like fusarin C, ent-pimara-8(14),15-diene, monodictyphenone, pseurotin A, sterigmatocystin, and lucilactaene, with roles ranging from structural to regulatory functions within these clusters.
Abd-B homeobox transcription factor (Abd-B_homeobox_TF)
Type: Family

The Abd-B homeobox protein family comprises sequence-specific transcription factors involved in a developmental regulatory system. These proteins confer specific positional identities to cells along the anterior-posterior axis during development. They play a crucial role in morphogenesis and the patterning of various body structures. Members of this family are characterized by the presence of a homeobox domain, which enables them to bind DNA and regulate the expression of target genes. The family's function extends to the regulation of key processes such as inflammation, where they are involved in the induction of endothelial cell surface molecules like SELE/E-selectin and VCAM1. Additionally, they can influence mRNA nuclear export and translation efficiency, impacting cellular protein synthesis.
MATH and coiled-coil domain-containing protein (MCC)
Type: Family

This family of proteins includes members with a MATH domain and coiled-coil domain, suggesting a role in protein-protein interactions. The MATH domain is typically involved in ubiquitination processes, while coiled-coil regions often mediate oligomerization or interactions with other proteins. One characterized member, RTM3, is known to be involved in plant defense by restricting the movement of a viral pathogen. Although the specific functions of other members are not detailed, they may be involved in similar biological processes, such as immune responses or cellular signaling pathways.
ATG15 Lipase (ATG15_Lipase)
Type: Family

The ATG15 lipase family is involved in the autophagic process, playing a crucial role in the degradation of intravacuolar contents. Members of this family are essential for the lysis of subvacuolar cytoplasmic components and autophagic bodies targeted to the vacuole, as well as the disintegration of intravacuolar multivesicular body (MVB) vesicles. This disintegration process is vital for cellular life span extension. The ATG15 lipases are implicated in various cellular functions, including vegetative growth, reproduction, and virulence in some species. Additionally, they contribute to the biosynthesis of certain virulence factors, such as deoxynivalenol in pathogenic fungi. All members belong to the AB hydrolase superfamily, characterized by a common structural fold and catalytic mechanism.
pH-response transcription factor pacC/RIM101 (pacC/RIM101)
Type: Family

The pacC/RIM101 family comprises transcription factors that regulate gene expression in response to ambient pH changes. Members of this family activate transcription of alkaline-expressed genes and repress acid-expressed genes when the ambient pH is alkaline. They are involved in various physiological processes, including virulence, mating, sporulation, and invasive growth in different fungal species. Some members specifically recognize and bind to DNA consensus sequences, contributing to the precise regulation of target genes. The activity of these transcription factors is critical for adapting to environmental pH shifts and is essential for the pathogenicity and lifecycle of the organisms.
Transcriptional regulator/dioxygenase, bacterial-type (TransReg_Diox_bact_type)
Type: Family

The protein family includes transcriptional regulators that control various metabolic and developmental processes in bacteria. Members of the family are involved in the regulation of short-chain fatty acid catabolism, glyoxylate cycle (RamB), propionate degradation, and cholesterol utilisation. They act as transcriptional activators or repressors, depending on the presence of specific carbon sources or stress conditions. Some proteins within the family regulate the expression of genes involved in biofilm formation, sporulation, and the stress response to antibiotics . Additionally, the family encompasses proteins that control the expression of restriction-modification systems and those that respond to environmental stresses such as radiation and desiccation such as DdrOC from Deinococcus deserti . The family also includes non-heme iron-dependent dioxygenases involved in the biosynthesis of antibiotics and other metabolic pathways including HPPE and Methylphosphonate synthase (MPnS) .
Phage Integrase (Phage_Integrase)
Type: Family

The 'phage' integrase family comprises enzymes that are essential for the integration and excision of bacteriophage DNA into and from a host genome, respectively. These integrases catalyze site-specific recombination events, often requiring accessory proteins such as excisionase or integration host factors to form functional complexes known as intasomes. These complexes facilitate the precise insertion or removal of phage DNA at specific attachment sites within the host's genome. Some family members are also implicated in the mobility of conjugative elements, contributing to horizontal gene transfer among bacteria. The integrases share a common mechanism involving the catalytic activity of tyrosine recombinases, which cut and rejoin DNA strands during the recombination process.
Bacterial G3P & Sugar ABC Transporter Permeases (UgpAE/MalFG_permease)
Type: Family

The UgpAE/MalFG permease family is involved in the import of various substrates across bacterial inner membranes as part of ABC transporter complexes. Members of the UgpAE subfamily, such as UgpA, are predominantly responsible for the translocation of sn-glycerol-3-phosphate (G3P) across the membrane, a crucial step in phospholipid metabolism and glycerophosphate utilization. Some proteins in this family can also transport glycerophosphoryl diesters, which are hydrolyzed during transport. The MalFG subfamily members, like YcjO and AraP, are implicated in the uptake of different substrates, including arabinooligosaccharides and possibly other sugars. These permeases play a key role in nutrient acquisition and are essential for the survival and growth of bacteria in various environments.
Bacterial Secretion System Channel Protein (Bact_Secretion_Sys_Channel)
Type: Family

This family of proteins is involved in the formation of multimeric ring-shaped structures that create channels across the outer membrane of bacteria. These channels are essential for various secretion systems that transport proteins across the membrane. Some members are part of the type II secretion system (T2SS), which exports folded proteins, including enzymes and toxins. Others contribute to the type III secretion system (T3SS), also known as the injectisome, which injects effector proteins into eukaryotic host cells, playing a role in pathogenicity and host immune response evasion. Additionally, certain members are involved in the assembly and extrusion of bacteriophages, forming channels that allow phage particles to pass through the bacterial outer membrane. The family also includes proteins that may be involved in type IV piliation and localized adherence, contributing to bacterial colonization and biofilm formation.
Phosphate-binding ABC transporter substrate-binding (Phosphate_ABC_transporter)
Type: Family

This family of proteins is primarily involved in the transport of phosphate across the cytoplasmic membrane. They are components of the ABC transporter complex PstSACB, which is responsible for phosphate import into the cell. These proteins have a high affinity for inorganic phosphate, which they bind to facilitate its transport. Some members of this family have been implicated in host cell adhesion and may play a role in virulence by acquiring phosphate from the host. Additionally, certain members are inhibited by arsenate, pyrophosphate, and polyphosphates, but not by organic phosphates.
Prephenate/Arogenate Dehydrogenase (Preph/Arog_dehydrog)
Type: Family

The prephenate/arogenate dehydrogenase family consists of enzymes involved in the biosynthesis of aromatic amino acids, primarily tyrosine. Members of this family catalyze the NAD(+)-dependent oxidative decarboxylation of prephenate to form 4-hydroxyphenylpyruvate, a key step in the pathway. Some enzymes within this family can also catalyze the conversion of arogenate to tyrosine. These enzymes play a regulatory role in controlling the levels of tyrosine within the cell. Additionally, certain members are involved in the biosynthesis of secondary metabolites, such as antibiotics like novobiocin and chloramphenicol, by catalyzing the formation of specific intermediates. The family is characterized by a lack of chorismate mutase activity in some bacterial members, distinguishing them from bifunctional enzymes that possess both prephenate dehydrogenase and chorismate mutase activities.
Bacterial Sigma-70 Factor (Sigma-70_Factor)
Type: Family

The sigma-70 factor family is a group of bacterial initiation factors that facilitate the binding of RNA polymerase to specific promoter sites to initiate transcription. Members of the family are involved in various regulatory processes, such as heat shock response, sporulation, and cell differentiation. Sigma factors recognize and bind to consensus sequences in the promoters, with each subfamily typically directing the transcription of a distinct set of genes. For example, the RpoH subfamily regulates heat shock genes, while other subfamilies are responsible for sporulation-specific genes or fruiting body formation. The sigma factors are released from the RNA polymerase after initiation, allowing the core enzyme to proceed with transcription elongation.
Myo-inositol Transporter (Myo-inositol_Transporter)
Type: Family

The myo-inositol transporter family is characterized by proteins that facilitate the transport of myo-inositol across cellular membranes. Members of this family are predominantly part of the major facilitator superfamily and are involved in sugar transport, with a specific focus on myo-inositol, a molecule important for cell signaling and osmoregulation. Some family members are also capable of transporting inositol stereoisomers and other related compounds. These transporters are found in various organisms, including humans, yeast, plants, and other eukaryotes. They function as symporters, often coupling the transport of myo-inositol with protons (H+), and are integral to maintaining cellular inositol levels, impacting processes such as osmotic balance and nutrient uptake. Certain transporters within this family also play a role in the traversal of the blood-brain barrier, vacuolar sugar import, and may respond to environmental stressors by altering transport activity.
Transcription factor, fungi (TF_fung)
Type: Family

The protein family is comprised of transcription factors that regulate the expression of gene clusters involved in the biosynthesis of various secondary metabolites in fungi. These metabolites include mycotoxins, host-selective toxins, phytohormones, and compounds with potential pharmacological applications such as antitumor agents and cholesterol-lowering drugs. The transcription factors are responsible for the production of a wide range of structurally diverse compounds, including notoamides, agnestins, citrinin, azaphilones, and sorbicillinoids, among others. They play crucial roles in fungal physiology, ecological interactions, and pathogenicity by controlling the synthesis of these bioactive molecules.
Flavin-dependent Halogenases in Natural Product Biosynthesis (Flavin-dep_Halogenase_NPB)
Type: Family

The Flavin-dependent halogenase family is involved in the biosynthesis of various bioactive compounds with diverse functions, including antibiotics, mycotoxins, antifungal agents, and anticancer drugs. Members of this family catalyze the halogenation of organic substrates, typically by incorporating chlorine or bromine atoms into specific positions of the target molecules. This modification often plays a crucial role in the biological activity of the compounds, such as enhancing their antibiotic or cytotoxic properties. The family includes enzymes that modify different substrates, including tryptophan, polyketides, and other aromatic compounds, indicating a broad substrate specificity. The halogenation reaction is dependent on flavin adenine dinucleotide (FAD) as a cofactor, which is reduced to FADH2 and then used to facilitate the halogen transfer. The family's enzymes are characterized by their ability to perform regioselective and sometimes iterative halogenation, contributing to the structural diversity of natural products.
DjlA DnaK co-chaperone (DjlA_DnaK_co-chaperone)
Type: Family

The DjlA protein family includes co-chaperone proteins that interact with DnaK to regulate the expression of operons involved in the synthesis of colanic acid polysaccharide capsules. These capsules may enhance bacterial survival in extracellular environments. The family is characterized by a transmembrane domain that functions as a dimerization domain, facilitating the interaction with DnaK. Some family members are implicated in the RcsB/RcsC phosphotransfer signaling pathway, influencing the bacterial response to environmental stress.
Potassium channel, voltage-dependent, EAG/ELK/ERG-like, animal-type (KCNH_animal-type)
Type: Family

The KCNH potassium channel family consists of voltage-gated potassium channels that play a critical role in regulating the electrical excitability of cells. Members of this entry are mainly found in animals. These channels are characterized by their pore-forming alpha subunits, which mediate various potassium currents. The S4 segment, often serving as the voltage-sensor, contains positively charged amino acids crucial for function. Members of the family are involved in modulating channel properties through mechanisms such as cAMP and subunit assembly. Some are involved in specific physiological processes like heart rate regulation (IKr current) and cell proliferation and differentiation. The activity of these channels can be influenced by factors such as calmodulin binding and intracellular phosphatidylinositol phosphates .
Tripeptidyl-peptidase I and related peptidases (Tripeptidyl-peptidase_I)
Type: Family

This family of proteins includes lysosomal serine proteases with tripeptidyl-peptidase I activity, which may act as non-specific lysosomal peptidases generating tripeptides from the breakdown products produced by lysosomal proteinases. These enzymes require substrates with an unsubstituted N-terminus. Additionally, the family encompasses secreted tripeptidyl-peptidases that degrade proteins at acidic pHs and are implicated in virulence. Some members are known to be inhibited by specific protease inhibitors, indicating a regulatory mechanism for their proteolytic activity. The family plays a role in protein degradation and processing, contributing to various physiological processes, including virulence in certain species.
Major Facilitator Superfamily Sugar Transporter (MFS_Sugar_Transporter)
Type: Family

The Major Facilitator Superfamily Sugar Transporter family encompasses a range of proteins involved in the transport of sugars across cellular membranes. Members of this family function as facilitative glucose transporters, which are essential for the uptake of glucose and its distribution to various tissues, and do not require insulin for their activity. Some members are specifically required for the development of the cardiovascular system. Others operate as symporters, coupling the transport of sugars like D-xylose, galactose, and L-arabinose with protons, thereby utilizing the proton motive force to drive the uptake of these sugars into the cell. The family also includes transporters for myo-inositol and putative metabolite transport proteins, suggesting a broader role in the transport of various metabolites. Regulation of activity is observed in some members by uncoupling agents and glucose transport inhibitors.