SII-SWORD/CoKE huggingface dataset:
NADPH-dependent 7-cyano-7-deazaguanine reductase (NADPH_dep_7-cyano-7-deazaG_red)
Type: Family

This family of proteins includes enzymes that are involved in the biosynthesis of queuosine, a modified nucleoside found in the anticodon loop of tRNA. They catalyze the NADPH-dependent reduction of 7-cyano-7-deazaguanine (preQ0) to 7-aminomethyl-7-deazaguanine (preQ1), which is a late step in the queuosine pathway. These enzymes exhibit high specificity for their natural substrate preQ0. They are characterized by their membership in the GTP cyclohydrolase I family and are found across various bacterial species. The activity of these enzymes is essential for the proper functioning of tRNA and the accuracy of protein synthesis.
N-acetyl-gamma-glutamyl-phosphate reductase (NAGSA_dehydrogenase)
Type: Family

The NAGSA dehydrogenase family is involved in the biosynthesis of amino acids, specifically arginine and lysine. Members of this family are enzymes that catalyze the NADPH-dependent reduction of N-acetyl-5-glutamyl phosphate to yield N-acetyl-L-glutamate 5-semialdehyde. This reaction is a key step in the metabolic pathway that leads to the production of essential amino acids. The enzymes are characterized by their requirement for NADPH as a cofactor and are found across various organisms, indicating a conserved role in nitrogen metabolism. Some members of the family are also involved in the modification of the amino acid carrier protein LysW, participating in the conversion of [LysW]-aminoadipate 6-phosphate to [LysW]-aminoadipate 6-semialdehyde.
Methionine import ATP-binding protein MetN-like (MetN_ABC_transporter-like)
Type: Family

The Methionine Import ATP-binding Protein Family is involved in the transport of methionine across the cellular membrane . Members of this family are part of the ABC transporter complex MetNIQ, which is responsible for the energy-dependent uptake of methionine, an essential amino acid required for protein synthesis and various metabolic processes. The ATP-binding proteins within this family are crucial for energy coupling to the transport system, utilising ATP hydrolysis to translocate methionine into the cell. Some members also participate in the import of formyl-L-methionine and may be regulated by intracellular methionine levels. Additionally, variations within the family can transport other substrates such as phosphonates, arginine, and possibly other amino acids, indicating a broader role in nutrient acquisition.
8-amino-7-oxononanoate synthase class-II (AON_synthase_class-II)
Type: Family

This family of proteins includes enzymes that catalyze the decarboxylative condensation of pimeloyl-[acyl-carrier protein] and L-alanine to produce 8-amino-7-oxononanoate (AON), a precursor in the biotin biosynthesis pathway. Members of this family are pyridoxal 5'-phosphate (PLP)-dependent and share a common fold typical of class-II aminotransferases. The enzymes are involved in key metabolic processes, including the synthesis of sphingolipids and the formation of aminolevulinic acid, which is the first step in the biosynthesis of heme. Some family members also have broader substrate specificity and may participate in additional biochemical pathways.
IspD/TarI cytidylyltransferase, baterial-type (IspD/TarI_cytidylyltransf_bact)
Type: Family

This family includes cytidylyltransferases IspD/TarI from bacteria and plants.

The IspD/TarI cytidylyltransferase family is involved in the biosynthesis of isoprenoids via the non-mevalonate pathway, which is essential for various cellular processes. Members of this family catalyse the formation of 4-diphosphocytidyl-2-C-methyl-D-erythritol from CTP and 2-C-methyl-D-erythritol 4-phosphate (MEP). This reaction is a key step in the production of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), precursors for the synthesis of isoprenoids. Isoprenoids are vital for numerous biological functions, including electron transport, plant hormone biosynthesis, and the prenylation of proteins. The family includes two subfamilies: the IspD subfamily, which is involved in the synthesis of isoprenoids in bacteria, plants, and apicomplexan parasites, and the TarI subfamily, which participates in the synthesis of wall teichoic acids in Gram-positive bacteria by transferring the cytidylyl group of CTP to D-ribitol 5-phosphate.
SAICAR synthetase (SAICAR_synthetase)
Type: Family

The SAICAR synthetase family is responsible for an essential step in the de novo purine biosynthetic pathway. Members of this family catalyze the conversion of 4-carboxy-5-aminoimidazole ribonucleotide (CAIR) to 4-(N-succinylcarboxamide)-5-aminoimidazole ribonucleotide (SAICAR). This reaction is crucial for the biosynthesis of purine nucleotides, which are fundamental components of DNA and RNA and are also involved in energy transfer, metabolic regulation, and signaling processes. The activity of SAICAR synthetase is therefore vital for cellular growth and proliferation, and its function is conserved across a wide range of organisms.
Bacterial tyrosine recombinase XerC/XerD complex (Tyrosine_recombinase_XerCD)
Type: Family

This family of proteins includes tyrosine recombinases, which are enzymes that catalyze the cutting and rejoining of DNA molecules in a site-specific manner. They play a crucial role in various DNA transactions, including chromosome segregation, by resolving dimers of the bacterial chromosome into monomers. This process is essential for proper cell division. Additionally, these proteins contribute to the segregational stability of plasmids, which are extrachromosomal DNA molecules. Some members of this family are involved in the integration and excision of bacteriophage DNA into and out of the host genome, as well as the regulation of gene expression through inversion of DNA segments.
Polyketide and Nonribosomal Peptide Biosynthesis Enzymes (PKS_NRPS_Biosynth_Enz)
Type: Family

Members of this entry are involved in the biosynthesis of various polyketides, nonribosomal peptides, and hybrid compounds with diverse biological activities . These proteins are multifunctional enzymes that catalyse the assembly of complex molecular structures through iterative condensation, reduction, methylation, and cyclization reactions. They are responsible for producing natural products such as antibiotics, mycotoxins, pigments, and other secondary metabolites with applications in medicine, agriculture, and industry. The family includes non-reducing and highly reducing polyketide synthases (PKS), nonribosomal peptide synthetases (NRPS), and hybrid PKS-NRPS enzymes. These enzymes select and incorporate various starter and extender units, including acetyl-CoA, malonyl-CoA, amino acids, and other precursors, to construct the carbon backbones of the target compounds. The resulting products often undergo further tailoring by additional enzymes within their respective biosynthetic gene clusters to achieve the final bioactive structures.
Ribonuclease H (RNase_H)
Type: Family

The RNase H family comprises endonucleases that specifically degrade the RNA moiety of RNA-DNA hybrids. These enzymes play a crucial role in various biological processes, including DNA replication, where they remove RNA primers from Okazaki fragments during lagging strand synthesis. They also participate in maintaining genomic stability by preventing initiation of replication at non-oriC origins and are involved in the production of retron-derived multicopy single-stranded DNA. RNase H enzymes are regulated by the presence of divalent metal ions, with magnesium being required for activity and manganese acting as an inhibitor.
ABC Transporter, Small Molecule Importer (ABC_SmlMolc_Importer)
Type: Family

The protein family described here is involved in the import of various small molecules across the cellular membrane using ATP-binding cassette (ABC) transporters, a mechanism that couples ATP hydrolysis to the translocation of substrates. Members of this family are responsible for the energy-dependent import of compounds such as spermidine, putrescine, thiamine, sulfate, thiosulfate, molybdate, tungstate, and Fe(3+) ions. These proteins are part of larger ABC transporter complexes, which typically consist of multiple subunits that work together to transport substances into the cell. The import of these molecules is crucial for cellular processes such as growth, metabolism, and response to environmental stress. The family includes proteins with regulatory domains that may inhibit transport activity in response to intracellular concentrations of the transported molecules, ensuring homeostasis within the cell.
Energy-coupling factor transporter ATP-binding (ECF_ABC_transporter_ATP-bd)
Type: Family

The Energy-coupling factor (ECF) transporter ATP-binding protein family is involved in the transport of various substrates across the cell membrane. Members of this family are part of the ECF ABC-transporter complex, which is distinct from classic ABC transporters. These proteins utilize the energy from ATP hydrolysis to translocate a diverse range of substrates, including vitamins and other small molecules, into the cell. The ECF transporter complex typically consists of a substrate-specific component and an ATP-binding component, which is responsible for energy coupling. The transport process is highly specific and dependent on the presence of both the ECF transporter complex and the substrate-binding protein. Some family members are also involved in the uptake of essential nutrients like biotin, thiamine, and riboflavin, particularly under low substrate concentrations.
Bacterial ribosomal protein bL28 (Bacterial_rp_bL28)
Type: Family

The bacterial ribosomal protein bL28 family is involved in the assembly and function of the large subunit of the bacterial ribosome. Proteins in this family are typically associated with the ribosomal 50S subunit and play a role in protein synthesis by contributing to the structure and stability of the ribosome. As ribosomal proteins, they are essential for accurate and efficient translation of the genetic code into functional proteins, which is a fundamental process in all living cells.
Ferredoxin--NADP reductase type 2 (Ferredoxin-NADP_redctase_2)
Type: Family

The ferredoxin--NADP reductase type 2 family consists of enzymes that play a crucial role in electron transfer processes within cells. These proteins are involved in the reduction of NADP+ to NADPH, a key reaction in the photosynthetic and respiratory electron transport chains. The NADPH produced is essential for various biosynthetic reactions, including fatty acid and nucleotide synthesis, and for the detoxification of reactive oxygen species, contributing to the cell's redox balance and defense against oxidative stress.
Tissue factor pathway inhibitor/Kunitz-type serine protease inhibitor-like (TFPI/VKTCI-like)
Type: Family

This entry includes Tissue factor pathway inhibitor (TFPI) from animals and Kunitz-type serine protease inhibitors, also known as Venom chymotrypsin inhibitors (VKTCIs) which primarily function as inhibitors of serine proteases , with some members also exhibiting the ability to block voltage-gated potassium channels (Kv) such as Kunitz-type U15-theraphotoxin-Hhn1c from Chinese bird spider. These inhibitors are characterised by their Kunitz/BPTI domain, which is responsible for their protease inhibitory activity. The family includes toxins from various venomous organisms, such as snakes, scorpions, and sea anemones. Members of this family often have dual functions, inhibiting both serine proteases and ion channels, which contributes to their role in the defense mechanisms of the organisms that produce them. The inhibitory activities of these proteins are crucial for modulating processes like blood coagulation, inflammation, and neurotransmission, making them significant in both physiological and pathological contexts.
SIS family GmhA and DiaA subfamilies (SIS_GmhA/DiaA_subfam)
Type: Family

The SIS family GmhA subfamily proteins are primarily involved in the isomerization of sedoheptulose 7-phosphate to D-glycero-D-manno-heptose 7-phosphate, a reaction that is part of the biosynthetic pathway for ADP-L-glycero-D-manno-heptose. This compound is a precursor for the heptose moiety of lipopolysaccharides in Gram-negative bacteria, which are essential components of the outer membrane. The activity of these enzymes is crucial for the proper functioning of bacterial cell walls and for the virulence of pathogenic bacteria. The DiaA subfamily members within the SIS family are involved in the initiation of chromosomal replication by interacting with the DnaA initiator protein, which is essential for the timely and accurate duplication of the bacterial genome. The UPF0309 family proteins, however, are uncharacterized within this context and their function remains to be elucidated.
Translation factor GTPase superfamily members (TRAFAC_GTPase_members)
Type: Family

This family of proteins includes GTPases involved in various cellular processes, such as translation elongation, where they bind aminoacyl-tRNA to ribosomes, and translation termination, where they interact with release factors to mediate the end of protein synthesis. Some members are involved in the recognition and disassembly of stalled ribosomes, triggering mRNA decay pathways. Others participate in sulfur assimilation by catalyzing the adenylation of sulfate to produce adenosine 5'-phosphosulfate. They are part of the TRAFAC class translation factor GTPase superfamily and exhibit diverse functions across different biological contexts.
Competence-damage inducible protein CinA (CinA)
Type: Family

The CinA family proteins are associated with bacterial competence and damage inducible processes. They are implicated in the recycling of the byproducts of NAD consumption back to NAD, a critical function in cellular metabolism. Some members of the CinA family, specifically the PncC subfamily, possess nicotinamidemononucleotide (NMN) amidohydrolase activity, which is essential for the pyridine nucleotide cycle. However, not all CinA-like proteins exhibit this enzymatic function. The family includes proteins that, despite their similarity, do not have NMN amidohydrolase activity, indicating a potential diversity in function within the family.
tRNA sulfurtransferase, ThiI (tRNA_sulfurtransferase_ThiI)
Type: Family

The ThiI family proteins are involved in the biosynthesis of thiamine (vitamin B1) and the modification of tRNAs. They catalyze the ATP-dependent transfer of sulfur to tRNA, resulting in the production of 4-thiouridine at position 8, which serves as a near-UV photosensor. Additionally, they facilitate the transfer of sulfur to the sulfur carrier protein ThiS, forming ThiS-thiocarboxylate, a crucial step in the thiazole synthesis pathway within thiamine biosynthesis. The sulfur source for these reactions is provided as a persulfide by the enzyme IscS.
Class-III Pyridoxal-phosphate-dependent Aminotransferase (Class-III_PLP-dep_AT)
Type: Family

The protein family is involved in amino acid metabolism, specifically in the transamination reactions that are crucial for the synthesis and degradation of various amino acids. Members of the family function as aminotransferases, enzymes that catalyze the transfer of an amino group from a donor molecule to an acceptor. Key reactions include the conversion of putrescine to GABA via 4-aminobutanal, the interconversion of ornithine and glutamate semialdehyde, and the transamination of N(2)-succinylornithine and alpha-ketoglutarate. Some members also participate in the arginine and lysine biosynthetic pathways, acting on substrates such as acetylornithine and succinyldiaminopimelate. The family is characterized by the presence of pyridoxal phosphate as a cofactor, which is typical for class-III pyridoxal-phosphate-dependent aminotransferases.
FMN-dependent NADH:quinone oxidoreductase, azoreductase type 1 (FMN-dep_NADH:Q_OxRdtase_AzoR1)
Type: Family

The azoreductase type 1 family consists of FMN-dependent enzymes that exhibit dual functionality. Members of this family primarily function as quinone reductases, providing resistance to thiol-specific stress caused by electrophilic quinones. They are also capable of azoreductase activity, catalyzing the reductive cleavage of azo bonds in aromatic azo compounds to produce the corresponding amines. This dual activity is essential for cellular defense against toxic electrophilic compounds and for the biodegradation of synthetic dyes. Some members may also act as nitroreductases, reducing nitro compounds to their corresponding amines. The enzymes typically require NADH as an electron donor for their reductase activities, and they may contribute to resistance against various quinone-related compounds.
Molybdenum cofactor biosynthesis MoaA/MoaC (MoCo_biosynth_MoaA/MoaC)
Type: Family

The MoaA/MoaC family is involved in the biosynthesis of the molybdenum cofactor (MoCo), which is essential for the activity of molybdoenzymes. Members of the MoaA family, part of the radical SAM superfamily, catalyze the cyclization of GTP to (8S)-3',8-cyclo-7,8-dihydroguanosine 5'-triphosphate, a crucial step in the early stages of MoCo biosynthesis. MoaC family members convert this cyclized GTP to cyclic pyranopterin monophosphate (cPMP), another key intermediate in MoCo biosynthesis. The MoaA/MoaC family proteins are found across a wide range of organisms, including bacteria, archaea, and eukaryotes, highlighting their fundamental role in cellular biochemistry. The coordinated action of MoaA and MoaC family proteins ensures the proper synthesis of MoCo, which is vital for various cellular processes such as nitrogen fixation, purine degradation, and sulfite detoxification.
Histidinol-phosphate aminotransferase (HistidinolP_aminotransfase)
Type: Family

The Histidinol-phosphate aminotransferase family is involved in the biosynthesis of the amino acid histidine. Members of this family are pyridoxal phosphate (PLP)-dependent enzymes that catalyze the transamination reaction converting histidinol phosphate to histidinol, a precursor of histidine. This reaction is a key step in the histidine biosynthetic pathway. Some family members may also transaminate aromatic amino acids and histidine, in addition to histidinol phosphate. The family belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family, which is characterized by the ability to transfer amino groups from amino acids to alpha-keto acids, playing a critical role in amino acid metabolism.
ABC transporter carbohydrate import ATP-binding proteins (ABC_carbohydrate_import_ATPase)
Type: Family

This family of proteins is involved in the transport of various carbohydrates across cellular membranes. They are part of the ATP-binding cassette (ABC) transporter superfamily, which utilize the energy derived from ATP hydrolysis to translocate substrates. Members of this family are typically part of larger transporter complexes that are responsible for the import of specific sugars such as ribose, arabinose, xylose, and galactose, among others. These proteins play a crucial role in energy coupling to the transport system, ensuring the uptake of essential nutrients for cellular metabolism and function.
Cyclin-dependent kinase (CDK)
Type: Family

The Cyclin-dependent kinase (CDK) family is crucial for cell cycle regulation, transcription, and other cellular processes. CDKs are serine/threonine protein kinases that, when activated by binding to cyclins, phosphorylate a variety of substrates to mediate cell cycle progression. Different CDK-cyclin complexes control specific transitions between cell cycle phases. Some family members also play roles in transcription regulation by phosphorylating the RNA polymerase II C-terminal domain, affecting elongation. Others are involved in developmental processes, DNA repair, apoptosis, and neuronal functions. Dysregulation of CDK activity is linked to cancer and other diseases.
HTH-type, TetR-like transcriptional regulator (HTH-type_TetR-like_transc_reg)
Type: Family

This entry represents proteins containing a homeobox-like domain and a C-terminal domain found in a number of different TetR transcription regulator proteins. The homeobox-like domain binds DNA through a helix-turn-helix (HTH) structure and is very similar in sequence and structure to domains in a wide range of DNA-binding proteins. These proteins are involved in various cellular processes such as osmoprotectant biosynthesis, lipid utilization, antibiotic resistance, and cell division. Members of the family are predominantly from bacteria, but also some homologues from archaea and eukaryotes, and includes, but not limited to, the following:

Nucleoid occlusion factor SlmA, a DNA-associated cell division inhibitor that is directly involved in preventing Z ring assembly on portions of the membrane surrounding the nucleoid

HTH-type transcriptional regulator BetI, a repressor involved in the biosynthesis of the osmoprotectant glycine betaine from choline

HTH-type transcriptional regulator EthR, a repressor from Mycobacterium tuberculosis implicated in ethionamide drug resistance

HTH-type transcriptional regulator RutR, a master transcriptional regulator that represses the degradation of pyrimidines and purines from Escherichia coli

HTH-type transcriptional regulator UidR, a repressor for the uidRABC operon

HTH-type transcriptional regulator AcnR, a repressor of the aconitase gene

HTH-type transcriptional regulator KstR2, a repressor of a small regulon that may play a role in the utilization of cholesterol
Glyoxalase II family hydroxyacylglutathione hydrolases (Glyoxalase_II_hydrolase)
Type: Family

The Glyoxalase II family proteins are thiolesterases that catalyze the hydrolysis of S-D-lactoyl-glutathione to produce glutathione and D-lactic acid. This reaction is part of the detoxification pathway for methylglyoxal, a byproduct of glycolysis that is toxic to cells. Efficient removal of methylglyoxal is crucial for cell health, as it can react with DNA, proteins, and other macromolecules, leading to advanced glycation end-products associated with aging and chronic diseases. Members of this family are characterized by their membership in the metallo-beta-lactamase superfamily, indicating a shared structural domain that coordinates metal ions essential for catalytic activity. The family is ubiquitous in bacteria, with members playing a significant role in the detoxification process, contributing to cellular defense mechanisms against glycolytic byproducts.
C-type lectin and snaclec domain-containing protein (C-type_lectin/snaclec_domain)
Type: Family

This family of proteins includes C-type lectins and snaclecs, which are known for their carbohydrate recognition domains. They are involved in a variety of biological processes, including cell-cell adhesion, immune response, and pathogen recognition. Members of this family can bind to specific carbohydrate structures on cell surfaces, leading to cell agglutination or modulation of signaling pathways. Some proteins in this family are involved in hemostasis, interfering with platelet aggregation or the coagulation cascade. They may act as anticoagulants by binding to coagulation factors or platelet receptors, or as procoagulants by inducing platelet aggregation. The functions of these proteins are often calcium-dependent and can be influenced by the presence of specific sugars or metal ions.
Urease Alpha Subunit (Urease_alpha_subunit)
Type: Family

The Urease Alpha Subunit family consists of enzymes that catalyze the hydrolysis of urea into ammonia and carbon dioxide, a reaction that plays a crucial role in nitrogen metabolism. This enzymatic activity is essential for organisms that utilize urea as a nitrogen source. Additionally, the production of ammonia can contribute to the survival of pathogenic bacteria by neutralizing acidic environments, such as the stomach, facilitating colonization and persistence within the host. Members of this family are characterized by their metallo-dependent hydrolase activity, requiring nickel ions for their catalytic function. The urease alpha subunit is part of the larger urease complex, which is typically composed of multiple subunits that work together for effective enzymatic activity.