SII-SWORD/CoKE huggingface dataset:
Glutamate Synthase (Glutamate_Synthase)
Type: Family

The glutamate synthase family is involved in the biosynthesis of glutamate, a critical amino acid for protein synthesis and a key metabolite in nitrogen metabolism. Members of this family are responsible for the conversion of L-glutamine and 2-oxoglutarate to L-glutamate, which is an alternative pathway to the one catalyzed by L-glutamate dehydrogenase. In plants, these enzymes play a significant role in the assimilation of ammonium, particularly in non-photorespiratory conditions and in the assimilation of symbiotically fixed nitrogen into amino acids in root nodules. Some family members are specific for NADH, while others utilize NADPH as an electron donor. The activity of these enzymes can be regulated by various metabolites and conditions, indicating their importance in the cellular nitrogen and carbon balance.
Cytochrome c-dependent Peroxidase and MauG (Cytochrome_c_Peroxidase/MauG)
Type: Family

The protein family encompasses enzymes with peroxidase activity, primarily reducing hydrogen peroxide (H2O2) to water using reduced cytochrome c as an electron donor. Members are involved in various biological processes, including iodate respiration, where they play a role in detoxifying H2O2 produced by iodate reductases. Some family members are essential for the biosynthesis of tryptophan tryptophylquinone (TTQ), a cofactor of methylamine dehydrogenase (MADH), thus participating in methylamine metabolism. Others are involved in the anammox process, reducing nitric oxide to hydroxylamine, contributing significantly to the Earth's nitrogen cycle. The family's structural features include domains reminiscent of class 1 cytochromes c and, in some cases, calcium-binding sites with unique ligand sets.
Bacterial Antiviral Defense Nuclease (Bact_Antivir_Def_Nuclease)
Type: Family

The protein family is involved in antiviral defense mechanisms across various bacterial species. Members of the family function as components of complex systems that confer resistance to bacteriophages. These systems often include an ATPase component, a reverse transcriptase, a non-coding RNA, and a nuclease. The nucleases within the family exhibit diverse activities, including endonuclease and exonuclease functions, targeting double-stranded DNA and sometimes RNA. Some members are regulated by nucleotide levels, becoming active when nucleotide concentrations drop, such as during viral replication. Others are ATP-dependent, with ATP enhancing their nuclease activity. The family includes proteins that are part of the Gabija, Retron, and Septu antiviral defense systems. They play roles in cleaving phage DNA, slowing down or preventing phage replication, and thereby protecting the host bacteria from viral infection.
Zinc-containing alcohol dehydrogenase-like protein (Zn-ADH-like_protein)
Type: Family

This family of proteins includes enzymes that are primarily involved in redox reactions, specifically the reduction of quinones and other related compounds. Members of this family are characterized by the presence of a zinc-binding motif, which is typical of zinc-containing alcohol dehydrogenase enzymes. These proteins are known to catalyze reactions such as the NADPH-dependent reduction of acrylyl-CoA to propanoyl-CoA and the reduction of prostaglandins. Some members are implicated in the biosynthesis of bioactive compounds, such as terrequinone A, an antitumor agent. The family also includes proteins that may play a role in metabolic processes and have been linked to the regulation of transcriptional activity and adipocyte differentiation.
Polysaccharide Deacetylase (Polysacch_Deacetylase)
Type: Family

The polysaccharide deacetylase family includes enzymes that catalyze the N-deacetylation of poly-beta-1,6-N-acetyl-D-glucosamine (PNAG or PIA), a biofilm adhesin polysaccharide. This modification is essential for the attachment of the polysaccharide to the bacterial cell surface, as it introduces positive charges into the neutral PIA polymer, facilitating electrostatic interactions. The deacetylation process is a critical step in biofilm formation, colonization, and contributes to bacterial virulence by enhancing resistance to neutrophil phagocytosis and human antibacterial peptides. Some family members are also specific to the heteropolysaccharide gellan, cleaving its glycosidic bonds to release tetrasaccharide units. The family plays a significant role in bacterial pathogenicity and biofilm-related infections.
RNA-guided DNA endonucleases/Transposases (RNA-guided_DNA_endo/Transpos)
Type: Family

The protein family includes RNA-guided DNA endonucleases and transposases. Members of the family are involved in adaptive immune defense mechanisms against mobile genetic elements such as viruses, transposable elements, and plasmids. They function by recognizing specific DNA sequences and cleaving DNA in a staggered manner, producing 5'-overhangs. The cleavage occurs downstream of a transposon-associated motif (TAM) when guided by RNA derived from the right-end element of an insertion sequence. Some members also have a role in inhibiting transposition activity of certain IS elements and may participate in homology-directed repair processes. The family exhibits a bilobed structure with distinct recognition and nuclease lobes, and some members are associated with the CRISPR (clustered regularly interspaced short palindromic repeat) system, utilizing CRISPR RNA (crRNA) for target DNA recognition and cleavage.
HAD-like hydrolase superfamily enzymes (HAD-like_hydrolase)
Type: Family

This family of proteins includes enzymes that are part of the HAD-like hydrolase superfamily. Members of this family are involved in various biochemical processes, such as the dephosphorylation of different substrates including D,L-glyceraldehyde 3-phosphate, 5-amino-6-(5-phospho-D-ribitylamino)uracil, flavin mononucleotide (FMN), and O-phospho-L-serine. These activities suggest roles in glycolysis, riboflavin biosynthesis, and amino acid metabolism. Some family members are also implicated in the regulation of cellular dormancy and persistence. The enzymes are characterized by their ability to catalyze the hydrolysis of phosphate esters, a reaction that is central to various metabolic pathways. The family includes specific subfamilies such as the NANP family, which is involved in the dephosphorylation of N-acylneuraminate-9-phosphate and is regulated by inhibitors like vanadate and calcium.
Bacterial Cell Wall Glycosylation GtrA (GtrA_CellWall_Glycosyl)
Type: Family

The GtrA family proteins are involved in various glycosylation processes essential for bacterial cell wall integrity and function. Members of this family participate in the translocation of bactoprenol-linked glucose across the cytoplasmic membrane, a critical step in O antigen modification. Some proteins within the GtrA family are also implicated in the decoration of cell wall teichoic acid with galactose and glucose, contributing to the structural diversity and functionality of the bacterial cell envelope. Additionally, certain GtrA family members act as anchor proteins that recruit arabinosyl transferases for the arabinosylation of arabinogalactan, a vital component of the mycobacterial cell wall. This recruitment is crucial for the biosynthesis of arabinogalactan, highlighting the family's role in maintaining cell wall architecture and integrity.
Ketopantoate Reductase-Related (KPR-Related)
Type: Family

This family of proteins includes enzymes that are primarily involved in the biosynthesis of pantothenic acid, a precursor for the synthesis of coenzyme A. Members of this family are known to catalyze the NAD(P)H-dependent reduction of ketopantoate to pantoic acid, which is a key step in the production of pantothenate. Some proteins within this family may also participate in the biosynthesis of host-selective toxins in certain plant pathogens, contributing to disease processes. The activity of these enzymes can be regulated by feedback inhibition mechanisms, such as the binding of coenzyme A, which can lead to conformational changes and inhibition of enzymatic activity.
NosZ/Cytochrome c oxidase subunit 2 (NosZ/Cyto_c_oxidase_sub2)
Type: Family

The NosZ/Cytochrome c oxidase subunit 2 family includes enzymes that play a crucial role in bacterial respiratory systems under anaerobic conditions. Nitrous-oxide reductase, a member of this family, is responsible for the reduction of nitrous oxide, a potent greenhouse gas, during the final step of the denitrification process. Additionally, the cytochrome c oxidase subunit 2 is essential for the electron transfer in the enzyme complex, facilitating the conversion of oxygen into water in the presence of cytochrome c. This family is characterized by a functional core formed by the interaction of its subunits, which are involved in the electron transport chain, highlighting their significance in both energy conservation and environmental protection.
Type II Toxin-Antitoxin System Antitoxin (TA_system_antitoxin)
Type: Family

This family of proteins includes antitoxin components of type II toxin-antitoxin (TA) systems. They function as mRNA interferase antitoxins, preventing the cessation of cell growth and inhibition of cell proliferation caused by their cognate toxins. Members of this family are involved in the regulation of cellular processes and stress responses, ensuring survival under adverse conditions by neutralizing the effect of toxins that would otherwise lead to cell stasis or death.
phD/YefM antitoxin (phD/YefM_antitoxin)
Type: Family

The phD/YefM antitoxin family comprises proteins that function as antitoxin components within type II toxin-antitoxin (TA) systems. Members of the family are involved in neutralizing the effects of various toxins, such as mRNA interferases, by binding to their respective promoters to repress transcription or by directly counteracting the toxins' activities. Some proteins within the family can form complexes with their cognate toxins, influencing the regulation of their own promoters. The family includes both characterized antitoxins with known toxin partners and orphan antitoxins where the cognate toxin is unknown. The antitoxins are implicated in maintaining cellular stability under stress conditions by preventing toxin-mediated inhibition of cell growth and proliferation. Although the specific roles and mechanisms may vary among family members, they all share a common function in providing a regulatory counterbalance to their associated toxins.
Phospholipase D domain-containing protein (PLD_domain)
Type: Family

This family of proteins includes enzymes with phospholipase and nuclease activities, which vary according to physiological conditions. They play a key role in mitochondrial dynamics, influencing both fusion and fission processes. The phospholipase activity involves the hydrolysis of cardiolipin to generate phosphatidic acid, a lipid signaling molecule that facilitates mitochondrial fusion. Conversely, its cleavage into diacylglycerol promotes mitochondrial fission. These proteins are also critical for the biogenesis of PIWI-interacting RNAs (piRNAs), which are essential for genome stability by silencing transposable elements, especially during spermatogenesis. The nuclease activity of these proteins produces intermediates for piRNA processing. Some members are implicated in virulence, and others are involved in cellular processes like growth, proliferation, and differentiation.
Bacterial outer membrane lipoprotein and surface antigen (Bact_OM_lipoprot/Surf_antigen)
Type: Family

This family of proteins includes outer membrane lipoproteins and surface antigens. The lipoproteins, such as SlyB and Pcp, are involved in various bacterial outer membrane processes, including potentially facilitating the uptake of nutrients like iron complexes. The surface antigens, identified in Rickettsia species, are likely involved in interactions with the host immune system and may play roles in pathogenicity and immune evasion. The exact functions of the uncharacterized proteins YcfJ and YfgH are not detailed, but they are noted to have similarity to Rickettsia surface antigens, suggesting a possible role in bacterial surface structure or host-pathogen interactions.
Binding-protein-dependent phosphate transport system permease (Phosphate_transprt_permease)
Type: Family

The phosphate transport system permease family is involved in the binding-protein-dependent transport system specific for phosphate. Members of this family are likely responsible for the translocation of phosphate across the cellular membrane. They are part of a larger complex that facilitates the uptake of phosphate, which is vital for various cellular processes including energy metabolism and nucleic acid synthesis. The permease proteins interact with the substrate-binding proteins and ATP-binding cassette transporters to import phosphate into the cell, playing a critical role in phosphate homeostasis and allowing cells to adapt to phosphate-limited environments.
Atypical kinase ADCK (Atypical_kinase_ADCK)
Type: Family

The ADCK protein kinase family is involved in the biosynthesis of coenzyme Q (ubiquinone), a vital lipid-soluble electron transporter for aerobic cellular respiration. Members of the family are atypical kinases with unclear substrate specificity, lacking traditional protein kinase activity. They are hypothesized to function as small molecule kinases, possibly lipid kinases phosphorylating a prenyl lipid in the ubiquinone biosynthesis pathway. These proteins are characterized by an atypical protein kinase-like fold with a KxGQ motif that occludes the substrate binding pocket, which becomes catalytically competent upon nucleotide-binding. Some members show unusual selectivity for ADP over ATP and are autoinhibited by their N-terminal domain.
Ferric/Cupric Reductase Transmembrane Component (Ferric/Cupric_Reductase)
Type: Family

The ferric reductase (FRE) family comprises enzymes that function as metalloreductases, facilitating the reduction of extracellular Fe(3+) to Fe(2+) and Cu(2+) to Cu(+). Members of the FRE family are involved in the reductive uptake of iron and copper from various sources, including Fe(3+)-salts and Fe(3+) bound to catecholate or hydroxamate siderophores. The reduced Fe(2+) and Cu(+) ions dissociate from their carriers and are subsequently imported into the cell via high-affinity transport systems. These proteins play a crucial role in iron and copper homeostasis and are essential for processes such as siderophore-mediated iron acquisition, vacuolar iron and copper reduction, and maintenance of cell wall integrity and mitochondrial function. Some family members are also implicated in the regulation of growth, development, and pathogen-host interactions.
Polyketide transferase af380 (Polyketide_trans_af380)
Type: Family

The polyketide transferase af380 family is involved in the biosynthesis of various secondary metabolites with diverse biological activities. Members of this family function as transferases, typically catalyzing the transfer of polyketide chains onto different molecular scaffolds, which are often part of larger biosynthetic gene clusters. These enzymes play crucial roles in the formation of complex natural products such as fujikurins, brefeldin A, fumagillin, phaeospelide A, aculenes, gregatins, and atranones. The biosynthetic pathways often involve multiple enzymatic steps, including cyclization, oxidation, and lactonization, to produce the final bioactive compounds. The family also includes thiohydrolases that may be involved in the release and macrolactonization of polyketide chains. The diverse functions of these enzymes underscore their importance in the production of compounds with potential pharmaceutical applications.
Formin Homology Diaphanous subfamily (Formin_Homology_Diaphanous_sf)
Type: Family

The Formin Homology family, specifically the Diaphanous subfamily, encompasses proteins that play a crucial role in the regulation of the actin and microtubule cytoskeletons. Members of this family are involved in actin nucleation and elongation, contributing to the assembly of F-actin structures like actin cables and stress fibers. They are essential for processes such as cytokinesis, cell migration, and maintaining cell shape. Some family members also participate in signaling pathways that link Rho GTPases and tyrosine kinases to actin dynamics. Additionally, these proteins can influence microtubule stability and are involved in various cellular functions, including Golgi organization, cilia assembly, and endosome dynamics. The family is characterized by conserved domains such as the FH2 domain, which is critical for actin filament nucleation and elongation, and the DAD domain, which regulates protein activation through autoinhibitory interactions.
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel (K/Na_HCN_channel)
Type: Family

The HCN channel family comprises hyperpolarization-activated ion channels that are weakly selective for potassium over sodium ions. These channels are integral for generating pacemaker currents in the heart and neurons, influencing the rhythm of the heartbeat and neuronal excitability. They are also implicated in sensory processes, such as responses to sour stimuli. HCN channels are regulated by cyclic nucleotides; cAMP and cGMP can activate the channels, leading to tetramer assembly and channel opening. The S4 segment likely serves as a voltage-sensor, with a pattern of positively charged amino acids. Activity can also be modulated by intracellular factors like chloride ions and pH levels. Some family members are sensitive to inhibition by compounds such as Cs(1+), ZD7288, and ivabradine.
Adenylate-forming Reductase (Adenylate-forming_Reductase)
Type: Family

The adenylate-forming reductase family is involved in natural product biosynthesis, resembling non-ribosomal peptide synthetases but typically modifying a single substrate rather than condensing multiple building blocks. Members activate substrate amino acids or carboxylic acids through an adenylation domain, link them as thioesters to a peptidyl carrier protein domain, and often feature a reductase domain for further processing. This family contributes to the biosynthesis of diverse compounds, including mycotoxins like fusaric acid, phytotoxins such as cichorine, and potential pharmaceuticals like ascochlorin and ascofuranone. Some members also participate in primary metabolism, such as phenylacetate-CoA ligases involved in phenylalanine metabolism. The family showcases versatility in substrate specificity, ranging from amino acids to aromatic and aliphatic acids, highlighting their role in the production of a wide array of bioactive secondary metabolites.
Lysosomal/Vacuolar Amino Acid Transporter 1 (LAAT-1)
Type: Family

The LAAT-1 family comprises lysosomal and vacuolar amino acid transporters that are specialized in the pH-dependent export of cationic amino acids such as arginine, histidine, and lysine. These transporters play a crucial role in maintaining amino acid homeostasis within the cell by mediating the efflux of these amino acids from lysosomal or vacuolar compartments. The function of the LAAT-1 family is essential for optimal growth in various organisms and may be involved in the degradation of autophagic substrates within autolysosomes, thus regulating lysosome function. Members of the LAAT-1 family are characterized by a di-leucine motif, which is critical for their lysosomal localization.
phD/YefM Type II Toxin-Antitoxin Antitoxins (phD-YefM_TA_antitoxins)
Type: Family

The phD/YefM antitoxin family consists of proteins that function as antitoxin components within type II toxin-antitoxin (TA) systems. These antitoxins neutralize the effects of their cognate toxins, thereby preventing harmful activity within the cell. The family is characterized by the ability of the antitoxins to interact with specific toxins (VapC proteins) and inhibit their toxic effects, which is crucial for maintaining cellular stability and preventing cell death under stress conditions. The antitoxins typically have a C-terminal domain that is essential for interaction with their cognate toxins, and this interaction specificity can be altered by exchanging the N-terminal domain with other antitoxins in the family. The family plays a significant role in the regulation of bacterial growth and survival.
Serine-Aspartate Repeat-Containing (SDr/BOS_complex)
Type: Family

The Serine-Aspartate Repeat-Containing Protein (SDr) family includes cell surface-associated calcium-binding proteins that play a crucial role in bacterial adhesion and pathogenesis. Members of the SDr family mediate interactions with extracellular matrix components, such as host NRXN1, to promote bacterial adhesion. Some family members specifically interact with bone sialoprotein, contributing to staphylococcal osteomyelitis and arthritis. Others bind to human fibrinogen, interfering with fibrin clot formation or promoting bacterial attachment, which may initiate foreign-body infections. The BOS complex subunits, also part of this family, are components of the multi-pass translocon (MPT) complex, facilitating the insertion of multi-pass membrane proteins into lipid bilayers. They take over after the SEC61 complex, occluding its lateral gate to promote the insertion of subsequent transmembrane regions.
Spondin/Thrombospondin type-1 domain-containing (Spondin/Thrombospondin_T1)
Type: Family

The Spondin/Thrombospondin type-1 domain-containing family is involved in cell adhesion, axon guidance, and the innate immune response. Members of the family promote attachment and neurite outgrowth in spinal cord and sensory neurons, contributing to axonal growth and guidance in the central and peripheral nervous systems. Some members also function as opsonins for macrophage phagocytosis of bacteria, binding to microbial components such as lipopolysaccharide, thus playing a role in the immune response. Additionally, they are involved in angiogenesis, actin cytoskeleton rearrangement, and may influence the expression of genes like notch1b, which is important for embryonic development and the function of the glomerular filtration barrier.
Lysine/N-terminal Methyltransferase Superfamily (Lys/N-term_MeTrsfase_sf)
Type: Family

The protein family includes methyltransferases that are part of the methyltransferase superfamily. Members are involved in post-translational modifications, specifically lysine and N-terminal methylation of various substrates, including citrate synthase and elongation factor 1-alpha (EEF1A1 and EEF1A2), playing roles in mitochondrial function and mRNA translation regulation. Some family members exhibit dual methyltransferase activity, catalyzing methylation at multiple sites of their targets. The activity of these enzymes is regulated by various metabolites and nucleotides, such as S-adenosylhomocysteine, oxaloacetate, GTP, and GDP. Additionally, one member is involved in the biosynthesis of sordarial, a salicylic aldehyde, by participating in a polyketide synthase pathway and contributing to the formation of an aromatic product from a reduced polyketide chain.
Ser/Thr Protein Kinases with Diverse Regulatory Roles (Ser_Thr_Kinases_DiverseReg)
Type: Family

The protein family includes serine/threonine-protein kinases with diverse functions in plants and animals. In plants, members are involved in hormone perception, such as brassinosteroids and phytosulfokines, regulating development and defense responses. Some act as receptors for peptide hormones, maintaining root stem cell niches or mediating systemic nitrogen-demand signaling. In animals, one member is a multifunctional kinase implicated in neuronal plasticity, innate immunity, autophagy, and vesicle trafficking. It regulates RAB GTPases, affecting processes like synaptic vesicle trafficking, ciliogenesis, and Golgi apparatus function. It also plays roles in apoptosis and innate immunity, independent of its kinase activity. Some members have predicted inactive kinase domains, suggesting possible regulatory or scaffolding roles rather than catalytic functions.