SII-SWORD/CoKE huggingface dataset:
Bacterial Cell Wall Synthesis and Modification (Bact_CellWall_Synth/Modif)
Type: Family

The protein family includes enzymes with diverse functions related to bacterial cell wall synthesis and modification, as well as antibiotic resistance. Members of the family are involved in the hydrolysis of D-amino acid-containing peptides, cleavage of Gly-Gly bonds in polyglycine linkers, and the liberation of D-alanyl moieties from teichoic acids. Some proteins within the family act as serine beta-lactamases, conferring resistance to cephalosporins by deactivating beta-lactam antibiotics. The family also includes proteins implicated in the biosynthesis of cyclic heptapeptides known as unguisins. These enzymes exhibit a range of regulatory mechanisms, including inhibition by beta-lactam compounds and other agents. Overall, the family plays crucial roles in bacterial cell wall maintenance, antibiotic resistance, and secondary metabolite production.
Bacterial metal-binding protein 9 (Bact_metal-bind_prot9)
Type: Family

The bacterial solute-binding protein 9 family is involved in the import of various metals, including zinc, manganese, iron, and potentially others, via ATP-binding cassette (ABC) transport systems. Members of this family bind their respective metals with high affinity and specificity, and deliver them to membrane permeases for translocation into the cytoplasm. Some proteins within the family also function as adhesins, contributing to adherence to the extracellular matrix and playing a role in pathogenesis and infection. The family includes proteins with additional domains that facilitate metal binding and acquisition, as well as proteins that may participate in protein-protein interactions with other metal-binding proteins.
FAD-dependent Monooxygenases in Biosynthesis and Metabolism (FAD-dep_Monooxygenase_BioMet)
Type: Family

The FAD-dependent monooxygenase family is involved in a wide range of biosynthetic pathways, catalyzing hydroxylation, epoxidation, and oxidative decarboxylation reactions. These enzymes play key roles in the production of mycotoxins, pigments, quorum sensing molecules, and various secondary metabolites with antimicrobial, antiproliferative, and insecticidal activities. They are also implicated in the degradation of environmental toxins and in the metabolism of compounds like urate. The family includes enzymes that modify the structure of polyketides, indole alkaloids, and flavonoids, contributing to the structural diversity and biological activity of natural products.
Serine/threonine and dual-specificity kinase (Ser_Thr_dual-spec_kinase)
Type: Family

This family of proteins includes serine/threonine and dual-specificity kinases that play roles in various cellular processes, including cell cycle regulation, DNA damage repair, transcription regulation, apoptosis, and cytoskeletal organization. Some members are involved in pre-mRNA splicing and stress responses, while others function in developmental processes such as neuronal growth, eye size regulation, and erythroid differentiation. These kinases can phosphorylate a range of substrates, including transcription factors, histones, and other kinases, influencing their activity, stability, and localization. They are also implicated in signaling pathways related to stress granule dynamics, mTORC1 signaling, and proteasomal degradation of key regulatory proteins.
Autophagy-related 22 and Lipoteichoic acid anchor flippase (ATG22/LtaA_families)
Type: Family

The ATG22 and LtaA protein families are involved in distinct cellular processes. The ATG22 family proteins function as vacuolar effluxers, mediating the efflux of amino acids from autophagic degradation, which is crucial for maintaining protein synthesis and cell viability during nitrogen starvation. They play a key role in autophagy, a cellular degradation pathway. On the other hand, the LtaA family proteins are proton-coupled antiporter flippases that catalyze the translocation of lipid-linked disaccharides, which anchor lipoteichoic acids to the cell membrane. This process is selective and essential for bacterial cell wall integrity and survival under acidic conditions during infection.
SNF2/RAD54 Helicase and DNA Repair (SNF2_RAD54_helicase_repair)
Type: Family

The SNF2/RAD54 helicase family is involved in various DNA repair processes, particularly homologous recombination (HR), a major pathway for repairing DNA double-strand breaks (DSBs), single-stranded DNA (ssDNA) gaps, and stalled or collapsed replication forks. Family members act as molecular motors during the homology search, guiding RAD51 ssDNA along a donor dsDNA and facilitating synaptic complex formation. They also play roles in transcription-coupled nucleotide excision repair, meiotic recombination, and the regulation of antigenic variation in kinetoplastid parasites. Additionally, some members function as DNA helicases, tension sensors, and chromatin remodelers, influencing the choice of DSB repair pathways and participating in the DNA damage response.
Major Facilitator Superfamily MdtG Subfamily (MFS_MdtG_subfamily)
Type: Family

The MdtG subfamily of the major facilitator superfamily (MFS) is involved in conferring resistance to a variety of substances, including fosfomycin and deoxycholate. Members of the MdtG subfamily function as multidrug resistance proteins, which are integral membrane transporters that facilitate the efflux of toxic compounds out of the cell, thereby contributing to the survival of the organism in the presence of antibiotics and other harmful agents. The activity of these proteins is essential for bacterial defense mechanisms against a range of antimicrobial substances.
Photosystem I assembly protein Ycf3 (Ycf3)
Type: Family

The Ycf3 family proteins are essential for the assembly of the photosystem I (PSI) complex in various photosynthetic organisms. Members of this family may function as chaperone-like factors, guiding the correct assembly of PSI subunits. The PSI complex is a critical component of the photosynthetic system, playing a pivotal role in the light-dependent reactions of photosynthesis by converting light energy into chemical energy. The Ycf3 family proteins are thus key to the proper functioning and maintenance of the photosynthetic machinery.
Phosphoenolpyruvate-dependent sugar PTS enzyme (PEP-utilizing_PTS_enzyme)
Type: Family

The PEP-utilizing enzyme family encompasses proteins that are key components of the phosphoenolpyruvate-dependent sugar phosphotransferase system (sugar PTS), a major carbohydrate active-transport system. Members of this family are involved in the phosphorylation and translocation of sugar substrates across the cell membrane. The general (non sugar-specific) component, known as Enzyme I, transfers the phosphoryl group from phosphoenolpyruvate (PEP) to the phosphoryl carrier protein (HPr). The proteins in this family are characterized by a domain architecture that includes an N-terminal domain with the HPr binding site, a central domain harboring the pyrophosphate/phosphate carrier histidine, and a C-terminal domain that binds pyruvate. Some members also participate in the transport of specific sugars like fructose, and may have additional domains for signal perception or multifunctional roles.
Phosphate Acetyltransferase/Butyryltransferase (Phos_Acetyltrans/Butyryltrans)
Type: Family

The Phosphate Acetyltransferase and Butyryltransferase family comprises enzymes involved in acetate metabolism, catalyzing the reversible interconversion of acetyl-CoA and acetyl phosphate, as well as the conversion of butyryl-CoA to butyrate via butyryl phosphate. These enzymes play a key role in the energy metabolism and regulation of acetylation potential in various bacteria. Members of the family are characterized by a conserved C-terminal substrate-binding site and an N-terminal region important for quaternary structure. Some family members are also involved in the metabolism of ethanolamine, propionate, and 1,2-propanediol, contributing to bacterial survival and pathogenicity.
Isocitrate and isopropylmalate dehydrogenases (ICDH/IPMDH)
Type: Family

This family of proteins includes enzymes that catalyze the oxidative decarboxylation of various substrates. Members of this family are involved in key metabolic pathways, such as the tricarboxylic acid cycle and the leucine biosynthesis pathway. They function by oxidizing specific substrates, which typically results in the formation of a keto acid and the release of carbon dioxide. Some family members have dual roles, participating in both glutamate and lysine biosynthesis, and can utilize NAD(+) as a cofactor. Other members exhibit broader substrate specificity, capable of catalyzing reactions involving tartrate, malate, and isocitrate. The enzymatic activities of this family are essential for various cellular processes, including energy production and amino acid synthesis.
Eukaryotic RNA-binding (Euk_RNA-bind_prot)
Type: Family

The RNA-binding protein family is involved in various cellular processes, including pre-mRNA splicing, ribosome assembly, DNA replication, and stress response. Members of the family bind to specific RNA or DNA motifs, influencing gene expression and protein synthesis. Some proteins within the family are implicated in circadian rhythm regulation, apoptosis, and cellular differentiation. Others play roles in chloroplast RNA processing and stabilization, contributing to photosynthesis and plant development. Additionally, certain family members are involved in innate immune response regulation and centriole biogenesis, ensuring proper cell division and response to pathogens.
cAMP-dependent protein kinase regulatory subunit-like (cAMP-dep_PK_reg_su-like)
Type: Family

cAMP-dependent kinase regulatory subunits play a crucial role in cAMP signaling within cells. They are involved in the regulation of protein kinases (PKA) activity by inhibiting the kinase in the absence of cAMP . Upon binding of cAMP, these regulatory subunits undergo a conformational change that leads to the dissociation of the regulatory subunit dimer from the catalytic subunits, thus activating the kinase . This family is involved in various cellular processes including the regulation of metabolic pathways, cell growth, and proliferation, as well as the rhythmic contraction of muscles and neuronal activity regulation in the brain .

This entry also contains cAMP/cGMP-dependent 3',5'-cAMP/cGMP phosphodiesterase B, thought to function as a cAMP-stimulated cAMP-phosphodiesterase which may play a role in regulating the cAMP relay response .

Acetyltransferase Pat catalyses the acetylation of the epsilon-amino group of a highly conserved lysine residue in acetyl-CoA synthetase (ACS) and of the universal stress protein (USP) MSMEG_4207. Acetylation results in the inactivation of ACS activity and could be important for mycobacteria to adjust to environmental changes .
Immunoglobulin superfamily BTN/MOG domain-containing protein (IgSF_BTN/MOG)
Type: Family

This family of proteins is involved in various immune functions, including the modulation of T-cell-mediated responses, such as activation, proliferation, cytokine production, and development of cytotoxicity. Members of this family may act as costimulatory signals for T-cell and B-cell responses, influencing both adaptive and innate immune mechanisms. Some proteins within this family are implicated in cell-cell adhesion processes, particularly in the context of myelin sheath maintenance and cell communication. Additionally, they may play roles in the negative regulation of T-cell proliferation, and in the case of tumor macrophages, contribute to the suppression of tumor-associated antigen-specific T-cell immunity. Certain members are also involved in the secretion of milk-fat droplets and may act as receptors for the association of cytoplasmic droplets with the apical plasma membrane.
WD repeat-containing protein 55/POC1 (WDR55/POC1)
Type: Family

The WDR55/POC1 family is characterised by the presence of WD repeat domains and is involved in various cellular processes. Members of the WDR55 subfamily are nucleolar proteins that modulate rRNA synthesis and play a central role in organogenesis. They are implicated in the development of the thymus and other organs . The POC1 subfamily members are centriolar proteins that play a crucial role in centriole assembly, stability, and ciliogenesis. They are involved in the early steps of centriole duplication and the later steps of centriole length control, ensuring centriole integrity and proper mitotic spindle formation. Additionally, they are required for primary cilia formation, ciliary length, cell proliferation, and retinal integrity. The family is essential for various developmental processes across a range of organisms.
Platelet-derived/Vascular endothelial growth factor (PDGF/VEGF_growth_factor)
Type: Family

The PDGF/VEGF growth factor family is involved in various processes such as angiogenesis, vasculogenesis, and endothelial cell growth. Members of the family function as growth factors that stimulate endothelial cell proliferation, migration, and survival while inhibiting apoptosis. They are key regulators of blood vessel permeabilization and play roles in axon guidance and cell body migration during embryonic development. Some family members are also implicated in increasing vascular permeability during specific physiological processes like lactation. Additionally, certain snake venom VEGF subfamily proteins contribute to venom dispersion and prey subjugation by inducing vascular permeability and hypotension, mediated by nitric oxide production from VEGF-activated endothelium NO synthase. These proteins also promote angiogenesis and interact with specific VEGF receptors, with varying affinities for VEGFR1 and VEGFR2.
Methyltransferase Superfamily (Methyltransf_Superfamily)
Type: Family

The methyltransferase superfamily protein family is involved in a variety of biochemical processes, including the biosynthesis of antibiotics, secondary metabolites, and components of cell membranes. Members of the family catalyze the transfer of methyl groups from S-adenosyl-L-methionine to various substrates, such as aklanonic acid, malonyl-thioesters, and demethylmenaquinol. These methylation reactions are crucial for the production of clinically significant anthracyclines, the modification of phospholipids, and the biosynthesis of menaquinol, which is essential for electron transport in bacteria. Some family members are also implicated in the biosynthesis of specialized metabolites like gliotoxin, forosamine, and nocamycin, as well as in the regulation of toxin production in fungi. The family includes both characterized and uncharacterized proteins, with some members potentially acting as S-adenosyl-L-methionine-dependent methyltransferases without a clearly defined substrate.
Coenzyme A-transferase family III (CoA-transferase_III)
Type: Family

The CoA-transferase III family is characterised by its ability to catalyse the reversible transfer of coenzyme A (CoA) from acyl-CoA thioesters to various acceptor molecules, playing a crucial role in diverse metabolic pathways . Members of this family are involved in the metabolism of L-carnitine, bile acids, and branched-chain fatty acids, as well as in autotrophic carbon dioxide fixation and the glyoxylate assimilation cycle. They facilitate the interconversion of stereoisomers of alpha-methyl-branched-chain fatty acyl-CoA esters and participate in the fermentation of amino acids via Stickland reactions. Additionally, they contribute to the ocean sulfur cycle by producing dimethyl sulfide from dimethylsulfonioproprionate. The family includes enzymes such as L-carnitine CoA-transferase, bile acid CoA-transferase, alpha-methylacyl-CoA racemase, and succinyl-CoA--L-malate CoA-transferase, each with specific substrate preferences and roles in cellular metabolism.
Cation transport ATPase (P-type) (Cation_transp_ATPase_P-type)
Type: Family

The cation transport ATPase (P-type) family is responsible for the active transport of cations across cellular membranes, utilizing ATP hydrolysis to drive the exchange of ions such as sodium, potassium, and hydrogen. Members of the family create electrochemical gradients essential for nutrient transport, cellular homeostasis, and various physiological processes including gastric acidification and sperm motility. Some subunits are regulated by cardiac glycosides like ouabain and are involved in maintaining electrolyte balance in epithelial cells of the kidney, colon, and airway epithelium.
AMP-activated protein kinase gamma/SDS23 families (AMPK_gamma/SDS23_families)
Type: Family

The AMP-activated protein kinase (AMPK) gamma subunit family and the SDS23 family are involved in distinct cellular processes. The AMPK gamma subunit family plays a crucial role in cellular energy homeostasis. It regulates energy metabolism by activating energy-producing pathways and inhibiting energy-consuming processes in response to ATP depletion. This family's members bind AMP, ADP, and ATP, leading to the activation or inhibition of AMPK. They are involved in phosphorylating metabolic enzymes and transcription regulators, affecting processes like protein, carbohydrate, and lipid biosynthesis, as well as cell growth and proliferation. Additionally, they contribute to cellular polarity by remodeling the actin cytoskeleton. The SDS23 family members are implicated in DNA replication and cell separation, with some involved in sexual development and mitosis. Despite the different functions, both families share a common feature of having CBS domains that mediate nucleotide binding.
Sulfate Adenylyltransferase/APS Kinase (Sulf_AdTrans/APS_kinase)
Type: Family

The sulfate adenylyltransferase and APS kinase family is involved in the intracellular assimilation of sulfate. Members of this family catalyze the formation of adenosine-5'-phosphosulfate (APS) from inorganic sulfate and ATP, a key step in the biosynthesis of sulfur-containing amino acids. Some proteins within the family have a non-functional APS kinase domain that is implicated in allosteric regulation by 3'-phosphoadenosine 5'-phosphosulfate (PAPS). Binding of PAPS to this domain induces a conformational change that decreases the substrate affinity of the enzyme. This regulatory mechanism ensures the proper balance of activated sulfate within the cell.
RavA family ATPases (RavA_ATPases)
Type: Family

The RavA family proteins function primarily as ATPases and are implicated in various cellular processes. They are suggested to have a role in metal ion insertion, potentially acting as metal-chelatases, or may serve as chaperones. The ATPase activity of RavA family members is crucial for their function, and in some cases, this activity can be regulated by interaction with other proteins, such as CadA, which may enhance ATPase activity under specific stress conditions. The family is characterized by a conserved domain that defines its membership and is found across various bacterial species.
WAP four-disulfide core domain (WAP_four-disulfide_core)
Type: Family

The WAP four-disulfide core domain family encompasses a group of proteins characterized by a conserved WAP-type four-disulfide core domain. Members of this family are involved in a variety of biological functions, primarily acting as protease inhibitors. They exhibit a broad range of inhibitory activities against proteases such as trypsin, chymotrypsin, elastase, and cathepsin G. Some family members are implicated in modulating inflammatory and immune responses, particularly following bacterial infections or in response to intracellular parasites like L.major. They may also play roles in tissue remodeling, wound healing, and possibly in sperm maturation. Additionally, certain proteins within this family, particularly those classified as venom waprins, have been shown to damage bacterial membranes and exhibit antibacterial activity, although they do not display hemolytic or toxic effects in mammals. The diversity of functions within this family reflects the versatility of the WAP-type domain in providing protective roles in various biological contexts.
Bacterial Transpeptidases and Beta-Lactamases (Bact_Transpept/Beta-Lactamase)
Type: Family

The protein family includes transpeptidases that play a crucial role in bacterial cell wall biosynthesis. Members of the family are involved in the catalysis of cross-linking peptidoglycan layers, which is essential for maintaining cell shape, integrity, and division. Some proteins within the family are specific to the division septum, while others are involved in lateral cell wall synthesis. The family also includes beta-lactamases, which confer resistance to beta-lactam antibiotics by hydrolyzing them. The transpeptidases are commonly known as penicillin-binding proteins (PBPs) and are targets for beta-lactam antibiotics, which inhibit their activity by acylating a serine residue in the active site. The beta-lactamases are divided into different classes, with class-D beta-lactamases being represented in this family. These enzymes vary in their substrate specificity and inhibition by various compounds. Overall, the family is characterized by its involvement in peptidoglycan synthesis and antibiotic resistance mechanisms.
Olfactory G-protein coupled receptor (Olfactory_GPCR)
Type: Family

This family of proteins includes G-protein coupled receptors with a primary role in the detection of odorants. These receptors are involved in the sense of smell and are responsible for the recognition and discrimination of a wide variety of airborne molecules. The function of these receptors is typically mediated by G proteins that activate downstream signaling pathways, such as adenylyl cyclase, leading to a cellular response. Some members of this family may also play a role in sperm cell recognition and potentially in taste perception.
DNA Damage Response and Repair Kinase (DDR_Repair_Kinase)
Type: Family

This family of proteins includes serine/threonine kinases that play crucial roles in cellular responses to DNA damage and stress. They are involved in checkpoint signaling, DNA repair, cell cycle regulation, and maintenance of genomic stability. Members of this family are known to activate various substrates, including those involved in DNA replication, mitosis, and apoptosis. They often recognize a consensus sequence for substrate phosphorylation and can phosphorylate histone variants at sites of DNA damage, contributing to the DNA damage response mechanism. Some family members also participate in mRNA surveillance pathways, regulating nonsense-mediated mRNA decay. Additionally, they are implicated in processes such as ribosome assembly, transcription modulation, and innate immune responses.
Archaeal Rpo3/Eukaryotic RPB3 RNA Polymerase Subunit (Rpo3/RPB3_RNA_Pol_subunit)
Type: Family

The archaeal Rpo3/eukaryotic RPB3 RNA polymerase subunit family includes proteins that are essential components of DNA-dependent RNA polymerases, which are responsible for the transcription of DNA into RNA using ribonucleoside triphosphates. Members of this family are involved in the synthesis of mRNA precursors, functional non-coding RNAs, ribosomal RNA precursors, and small RNAs such as 5S rRNA, snRNAs, tRNAs, and miRNAs. They play a role in the assembly of the RNA polymerase complex, with some members containing an iron-sulfur cluster essential for this process. Additionally, certain subunits are implicated in transcription termination and RNA-directed DNA methylation-dependent transcriptional gene silencing of repeated sequences, including transposable elements. This family is characterized by a core element with a large central cleft and a clamp element that moves to open and close the cleft, indicating a role in the structural dynamics of the RNA polymerase during transcription.