SII-SWORD/CoKE huggingface dataset:
GLI C2H2-type zinc-finger (GLI_C2H2-zinc-finger)
Type: Family

The GLI C2H2-type zinc-finger protein family is characterized by its involvement in transcriptional regulation, with members acting as transcriptional activators or repressors. These proteins play crucial roles in various biological processes including neurogenesis, organogenesis of the central nervous system (CNS), left-right asymmetry specification, and neural crest development. They are known to bind DNA, often recognizing specific GLI-consensus sequences, and can influence the expression of genes related to cell fate determination and developmental patterning. Some family members are also implicated in cellular responses to environmental stressors such as zinc availability, contributing to homeostasis and adaptation.
Bacterial Outer Membrane Structural/Functional (Bact_OuterMem_StrucFunc)
Type: Family

The protein family is involved in various functions related to the structural integrity and function of the bacterial outer membrane. Members of the family play roles in maintaining the position of the peptidoglycan cell wall within the periplasm, acting as porins with low permeability for small solutes, and participating in cell division processes. Some proteins within the family are part of the Tol-Pal system, crucial for outer membrane invagination during cell division and outer membrane integrity. Others are involved in bacterial motility, forming part of the flagellar motor complex, or in antiviral defense systems. Additionally, certain members function in cell adhesion, biofilm formation, and resistance to environmental stress, including phage and colicin sensitivity. The family also includes proteins that may have roles in transport, ammonia secretion, and apoptosis induction in host cells.
Zinc finger (Zinc_finger)
Type: Family

The zinc finger protein family is characterized by the presence of zinc finger motifs, which are small protein domains that can coordinate one or more zinc ions to stabilize their folds. Members of this family are predominantly involved in transcriptional regulation, with many acting as transcription factors that bind DNA and regulate the expression of target genes. Functions of these proteins include roles in development, cell differentiation, immune response, and maintenance of cell identity. Some family members possess histone methyltransferase activity, influencing chromatin structure and gene expression. The diversity of zinc finger domains, such as C2H2-type, allows for a wide range of DNA-binding specificities and regulatory functions.
G-protein coupled receptor 2 (GPCR_2)
Type: Family

The G-protein coupled receptor 2 family is characterized by its involvement in diverse physiological processes through the binding of various peptide ligands, such as hormones and neuropeptides. Members of this family play pivotal roles in the regulation of metabolic pathways, stress responses, and developmental processes. They are typically composed of seven transmembrane helices and are coupled to G proteins, which activate adenylyl cyclase, leading to increased intracellular cAMP levels. Some receptors also couple to phospholipase C or inhibit calcium channels. Functions of these receptors include regulation of blood glucose levels, hormone secretion, smooth muscle relaxation, and modulation of neurotransmission and circadian rhythms. The specificity and diversity of ligand binding, along with the downstream signaling mechanisms, underscore the family's importance in maintaining homeostasis and responding to physiological changes.
Small Leucine-Rich Proteoglycans (SLRP)
Type: Family

The small leucine-rich proteoglycan (SLRP) family is involved in various biological processes including collagen fiber assembly, cell adhesion, migration, and axon guidance. Members of this family play roles in maintaining tissue structure, such as anchoring basement membranes to connective tissue, affecting the rate of fibril formation, and regulating biomineralization. Some SLRPs are involved in modulating signaling pathways, such as TGF-beta and BMP signaling, which are critical for cartilage homeostasis and osteoarthritis pathogenesis. They also contribute to the organization of the extracellular matrix, particularly in the cornea, where they help maintain transparency and stromal matrix structure. Additionally, certain SLRPs participate in neuronal development, guiding neuron placement and synapse density regulation.
Molybdenum import ATP-binding protein ModC (Molybdenum_import_ModC)
Type: Family

The ModC family of proteins is involved in the import of molybdenum, a vital trace element required for the activity of various enzymes. These proteins are part of the ABC transporter complex ModABC, which is responsible for the uptake of molybdate ions into the cell. ModC serves as the ATP-binding component of the complex, providing the necessary energy for the transport process. The presence of ModC is crucial for the function of the ModABC complex, as it couples the energy derived from ATP hydrolysis to the translocation of molybdate across the cell membrane, ensuring the availability of molybdenum for essential cellular processes.
ERT1/acuK gluconeogenesis transcription factor (ERT1_acuK_gluconeogen_tf)
Type: Family

The ERT1/acuK family comprises transcription factors that play a crucial role in the regulation of nonfermentable carbon utilization. Members of this family are primarily involved in the activation of gluconeogenetic genes, which are essential for metabolic pathways that generate glucose from non-carbohydrate sources. Some proteins within this family have been identified to specifically bind to DNA sequences in the promoter regions of target genes, indicating a direct mechanism of transcriptional regulation. The activity of these transcription factors is particularly important under conditions where fermentable carbon sources are scarce, necessitating the mobilization of stored or alternative carbon reserves to maintain cellular energy balance.
Chromosome-partitioning and nucleoid occlusion protein (Chromosome_partition/occlusion)
Type: Family

This family of proteins is involved in the process of chromosome partitioning and cell division . Members of this family, such as ParB, are known to bind to DNA at the origin of replication and localize to the cell poles following DNA replication completion . They play a crucial role in ensuring proper chromosome segregation by preventing the formation of the division machinery over the nucleoid, a process known as nucleoid occlusion. This function is particularly important under conditions that disturb the cell cycle, as it helps to coordinate cell division and chromosome segregation, thus preventing chromosome breakage. Some members of this family may also be involved in plasmid DNA partitioning, indicating a broader role in genetic material maintenance and stability.
L-rhamnose isomerase (L-rhamnose_isomerase)
Type: Family

The L-rhamnose isomerase family consists of enzymes that catalyze the reversible isomerization of L-rhamnose to L-rhamnulose. This reaction is a critical step in the catabolism of L-rhamnose, a deoxy sugar commonly found in plant cell walls and bacterial polysaccharides. Members of the L-rhamnose isomerase family are characterized by their ability to facilitate the conversion between these two sugar forms, playing a vital role in the utilization of L-rhamnose as a carbon source for various microorganisms. The enzymatic activity of these proteins is essential for the metabolic pathways that degrade complex carbohydrates, contributing to the versatility of microbial species in adapting to diverse ecological niches where L-rhamnose is present.
DNA integrity scanning protein DisA (DisA)
Type: Family

The DisA family proteins are involved in a DNA-damage checkpoint mechanism active prior to asymmetric division during sporulation. They form globular foci that rapidly scan chromosomes for lesions, pausing at damaged sites to trigger a temporary block in sporulation initiation. Additionally, they possess diadenylate cyclase activity, catalyzing the formation of cyclic di-AMP (c-di-AMP) from ATP. c-di-AMP acts as a signaling molecule linking DNA integrity with sporulation progression. An increase in c-di-AMP levels serves as a positive signal for sporulation to proceed; however, synthesis halts upon DNA damage detection. Some family members are regulated by interactions with RadA or nucleic acid structures, and their activity is essential for various cellular processes including growth, DNA repair, and cell wall homeostasis.
Cell Cycle and Stress Response Kinase (CC_SR_Kinase)
Type: Family

The protein family includes serine/threonine and tyrosine kinases that play crucial roles in cell cycle regulation, stress response, and translation initiation. Members of the family negatively regulate the transition from G2 to M phase in mitosis by phosphorylating CDK1, thus preventing premature mitotic entry. They are also involved in meiotic arrest and exit during oocyte maturation. Additionally, some family members sense metabolic stress and activate the integrated stress response by phosphorylating EIF2S1/eIF-2-alpha, leading to global protein synthesis inhibition and preferential translation of stress response mRNAs. This response is crucial for cellular adaptation to conditions such as amino acid starvation, unfolded protein response, and heme deficiency. The family also includes kinases that regulate the immune response to viral infection by phosphorylating EIF2S1/eIF-2-alpha, contributing to antiviral defense mechanisms.
Cytosolic Fe-S Cluster Assembly Factor (Cytosolic_Fe-S_CAF)
Type: Family

The NARF family proteins are essential components of the cytosolic iron-sulfur (Fe/S) protein assembly machinery. They are involved in the maturation of extramitochondrial Fe/S proteins, which are crucial for various cellular processes. Members of this family may also play a role in the transfer of pre-assembled Fe/S clusters to target apoproteins. Some proteins within this family appear to negatively regulate the level of HIF1A expression, although this effect could be indirect. The family is characterized by its involvement in the incorporation of iron-sulfur clusters into Fe/S proteins, which is a fundamental process for cell metabolism and regulation.
Serine/threonine-protein phosphatase PP1 catalytic subunit (PP1_catalytic_subunit)
Type: Family

This family of proteins includes serine/threonine-protein phosphatases that are involved in a wide range of cellular processes. They associate with regulatory proteins to form holoenzymes that dephosphorylate numerous biological targets. These enzymes are essential for cell division and participate in the regulation of glycogen metabolism, muscle contractility, and protein synthesis. They are involved in the control of chromatin structure, cell cycle progression, ionic conductances, and long-term synaptic plasticity. Some family members play roles in the regulation of circadian rhythms, chromosome cohesion during meiosis, and mitosis, as well as in stress responses, such as osmotic stress and endoplasmic reticulum stress. They are regulated by various inhibitors and can be inactivated by binding to specific proteins or inhibited by toxins.
High Mobility Group Box (HMGB) (HMGB)
Type: Family

The HMGB family proteins are multifunctional and redox-sensitive, with roles in various cellular compartments. In the nucleus, they act as DNA chaperones involved in replication, transcription, chromatin remodeling, V(D)J recombination, DNA repair, and genome stability. They preferentially bind to non-canonical DNA structures and can bend DNA to enhance flexibility and promote gene promoter activities. In the cytoplasm, they function as sensors or chaperones for immunogenic nucleic acids, mediating autophagy and activating TLR9-mediated immune responses. As danger-associated molecular pattern (DAMP) molecules, they amplify immune responses during tissue injury. Extracellularly, they bind to DNA, nucleosomes, and other molecules, activating cells through multiple surface receptors. Depending on their redox state, they can act as chemokines, cytokines, or induce immunological tolerance. They are also implicated in angiogenesis, platelet activation, neuronal outgrowth, and may influence the accumulation of polyglutamine proteins.
Ribosomal RNA Pseudouridine Synthase RsuA (RsuA_PseudoU_synthase)
Type: Family

The RsuA family of pseudouridine synthases is responsible for catalyzing the isomerization of specific uracil residues to pseudouridine in ribosomal RNA, a modification that is essential for the proper functioning of ribosomes. Members of the RsuA family exhibit specificity for different rRNA targets, including the synthesis of pseudouridine from uracil-516 in 16S rRNA and uracil-2457, uracil-2604, and uracil-2605 in 23S rRNA. Some members also display dual specificity, modifying both rRNA and tRNA, such as the conversion of uracil-35 in the anticodon of tRNA(Tyr). These enzymes play a crucial role in the structure and function of the ribosome, contributing to the fidelity of protein synthesis.
Peptidase M1 family aminopeptidases (Peptidase_M1_aminopeptidases)
Type: Family

The Peptidase M1 family is characterized by a broad specificity for aminopeptidase activity, playing a role in the digestion of peptides from hydrolyzed proteins by gastric and pancreatic proteases. Members are involved in processing various peptides, including peptide hormones, neuropeptides, and chemokines. They participate in antigen presentation, angiogenesis, cholesterol crystallization, and may regulate amino acid transport. Some act as receptors for coronaviruses, influencing microbial infection. The family includes enzymes that degrade oligopeptides, inactivate peptide hormones, and are implicated in blood pressure regulation, embryonic development, and immune responses.
Aliphatic Amidase/Beta-Ureidopropionase (Aliph_Amidase/BUP)
Type: Family

The Aliphatic Amidase and Beta-Ureidopropionase Family includes enzymes that catalyze the hydrolysis of various aliphatic amides to their corresponding organic acids with the release of ammonia. Members of this family also exhibit acyl transferase activity in vitro, transferring acyl moieties of short-chain amides to hydroxylamine to form hydroxamates. Some enzymes within this family are involved in the degradation of citrulline and polyamine biosynthesis, as well as the industrial production of beta-lactam antibiotics through the hydrolysis of N-carbamoyl-D-amino acids. The family belongs to the carbon-nitrogen hydrolase superfamily and includes formamidases with restricted substrate specificity for formamide, N-carbamoyl-D-amino acid hydrolases, beta-ureidopropionases involved in pyrimidine degradation, and nitrilases. These enzymes play roles in nitrogen metabolism, antibiotic production, and plant and microbial nitrogen utilization.
Flavin-containing monooxygenases-like (FMO-like)
Type: Family

The FMO family comprises flavin-containing monooxygenases that play a crucial role in the metabolism of a wide array of nitrogen- and sulfur-containing compounds, including xenobiotics, drugs, and dietary components. Members of this family are involved in the detoxification of trimethylamine (TMA), converting it to trimethylamine N-oxide (TMAO), a process influenced by gut microbiota from dietary precursors such as choline and carnitine . This reaction is significant for regulating TMAO concentration, impacting platelet responsiveness and thrombus formation. Additionally, the family includes enzymes that catalyse the conversion of methylthioalkyl glucosinolates into methylsulfinylalkyl glucosinolates, and the oxidation of various other substrates, indicating a broad substrate specificity. Some members are also involved in the biosynthesis of secondary metabolites and pigments, as well as the oxidative metabolism of therapeutic drugs and insecticides. This entry also includes 4-hydroxybenzoate brominase that catalyses the bromination of 4-hydroxybenzoate (4-HBA) to 3-bromo-4-hydroxybenzoate, followed by bromination and decarboxylation of 3-bromo-4-hydroxybenzoate to 2,4-dibromophenol . The family's functions are essential for various physiological processes, including correct protein folding, cholesterol biosynthesis, glucose homeostasis, and systemic acquired resistance in plants.
Bacterial Beta-galactosidase (Bact_Beta-galactosidase)
Type: Family

The Beta-galactosidase family is composed of enzymes that catalyze the hydrolysis of beta-galactosides into monosaccharides. Members of the family are also capable of transglycosylation, which can result in the production of galacto-oligosaccharides (GOS). These enzymes are inhibited by various metal ions and chelating agents, and some are activated by specific cations. The family includes both large and small subunits of the enzyme, which may function together in a complex. Beta-galactosidases are involved in lactose degradation and are found across various bacterial species. They have applications in the dairy industry for lactose removal and GOS production.
Protein-Tyrosine Phosphatase (Protein-Tyr_Phosphatase)
Type: Family

The protein-tyrosine phosphatase family is involved in various cellular processes including cell growth control, T-cell activation, integrin-mediated focal adhesion formation, and negative regulation of insulin receptor signaling. Members of this family play roles in the dephosphorylation of tyrosine residues in proteins, which can modulate enzyme activity, protein-protein interactions, and cellular localization. Some members are involved in the negative regulation of pathways downstream of receptor signaling, contributing to immune responses and signal transduction pathways. Others are implicated in the establishment of contextual memory and differentiation of cells, such as the maturation of oligodendrocytes. Effector proteins within this family can alter host cell physiology to promote bacterial survival. The family includes both receptor-type and non-receptor class subfamilies, with some acting as virulence determinants in pathogenesis by dephosphorylating host proteins.
WD repeat LIS1/nudF dynein regulation (WD_LIS1/nudF_dynein_reg)
Type: Family

The WD repeat LIS1/nudF family is involved in the regulation of the minus-end directed microtubule motor protein dynein. Family members play a crucial role in cellular processes such as mitotic spindle positioning, nuclear migration, and microtubule-dependent transport. They may enhance dynein-mediated microtubule sliding by targeting dynein to microtubule plus ends and are essential for various dynein-dependent processes including Golgi integrity, transport of microtubule fragments, and centrosome coupling. Some members also participate in the inactivation of platelet-activating factor (PAF) by serving as regulatory subunits of the cytosolic type I PAF acetylhydrolase. They are implicated in neuronal development, including the proliferation and migration of neuronal precursors, and may influence cell locomotion and actin polymerization in response to calcium influx.
Complement & Cell Adhesion Regulators (Compl-Cell_Adhes-Reg)
Type: Family

The protein family is involved in various immune and developmental processes. Members act as cofactors for complement factor I, protecting cells from complement-mediated injury by cleaving C3b and C4b. They play roles in cell adhesion, mediating interactions between cells and the endothelium, and are implicated in lymphatic vascular development. Some members serve as receptors for pathogens, facilitating immune evasion or cell entry. Others are involved in reproductive processes, such as sperm-egg fusion, and in immune regulation by inducing T-regulatory cell differentiation. Additionally, they bind negatively charged substances, potentially regulating coagulation or complement cascades, and participate in the clearance of complement-opsonized pathogens.
Sensor protein kinase GraS-like (GraS-like)
Type: Family

The protein family is comprised of sensor protein kinases that are part of two-component regulatory systems, which are typically involved in detecting environmental signals and initiating appropriate cellular responses. These sensor kinases autophosphorylate on a histidine residue and transfer the phosphate to a response regulator, which then modulates the expression of various genes. The family regulates processes such as cell wall metabolism, virulence, biofilm production, oxidative stress resistance, and antibiotic resistance. This entry includes Sensor protein kinase GraS from Staphylococcus aureus, which is involved in resistance against cationic antimicrobial peptides (CAMPs) ; Sensor protein BceS from Bacillus subtilis, involved in the regulation of bacitracin resistance and Sensor-like histidine kinase SenX3 from Mycobacterium tuberculosis, which plays a role in the phosphate starvation response . Activity of these kinases can be regulated by factors such as zinc-binding, which negatively affects autophosphorylation, or environmental conditions like phosphate availability.
ATP-binding cassette subfamily G transporters (ABCG_transporters)
Type: Family

The ABCG family of ATP-binding cassette (ABC) transporters is characterized by its broad substrate specificity and involvement in various biological processes across different organisms. Members of this family actively extrude a wide range of compounds, including physiological metabolites, dietary toxins, and xenobiotics, often in an ATP-dependent manner. They play crucial roles in lipid transport, sterol homeostasis, porphyrin homeostasis, and the cellular efflux of heme. Some members are involved in the transport of pigment precursors in eye color determination, while others participate in plant defense responses, arbuscular mycorrhizal symbiosis, and abiotic stress responses in plants. Additionally, certain ABCG transporters are implicated in the exclusion of xenobiotics from the brain and contribute to multidrug resistance in cells. The family also includes transporters that mediate the export of signaling molecules like abscisic acid in plants and are essential for processes such as pollen fitness and vascular development.
Dihydroorotate dehydrogenase B electron transfer subunit (PyrK_electron_transfer)
Type: Family

The PyrK family proteins are primarily involved in the electron transfer process associated with the oxidation of dihydroorotate. They act as electron transfer subunits, channeling electrons from the FMN redox center in the PyrD type B subunit to the ultimate electron acceptor NAD(+). This function is crucial for the synthesis of pyrimidine nucleotides through the de novo pyrimidine biosynthesis pathway. Some family members also participate in metal reductase complexes, reducing various metal ions using NADH or NADPH as electron donors, which may play a role in microbial metal reduction and detoxification processes.
Arabidopsis F-box/kelch-repeat (F-box/kelch-repeat_ARATH)
Type: Family

The F-box/kelch-repeat proteins are involved in various cellular processes through the formation of SCF (SKP1-cullin-F-box) E3 ubiquitin ligase complexes. These complexes play a crucial role in the ubiquitination and subsequent proteasomal degradation of target proteins, thereby regulating protein turnover. Some proteins are also known to be involved in seed germination. The F-box domain is essential for the interaction with SKP1 (ASK in Arabidopsis), while the kelch repeats may be involved in substrate recognition .
Mitochondrial Respiratory Supercomplex Factor 1 (RCF1)
Type: Family

The RCF1 family comprises mitochondrial proteins that function as cytochrome c oxidase subunits, which are essential for the assembly of respiratory supercomplexes. These supercomplexes are involved in the mitochondrial respiratory chain, crucial for the reduction of oxygen to water. Members of the RCF1 family may also play roles in the recruitment of additional cytochrome c oxidase subunits and in maintaining a proper proton motive force across the inner mitochondrial membrane. This is vital for efficient ATP production and overall cellular respiration.