SII-SWORD/CoKE huggingface dataset:
Elongation factor Tu GTPase (EF-Tu_GTPase)
Type: Family

Elongation factor Tu (EF-Tu) proteins are essential GTPases responsible for catalyzing the delivery of aminoacyl-tRNA to the ribosome during protein synthesis. They bind to aminoacyl-tRNA in a GTP-dependent manner and escort it to the A-site of the ribosome, ensuring the correct match between the tRNA anticodon and mRNA codon. Upon codon recognition, GTP is hydrolyzed, leading to a conformational change in EF-Tu that releases the tRNA into the ribosome. EF-Tu also plays a role in the regulation of autophagy and innate immunity, particularly in its mitochondrial form. It can recruit ATG5-ATG12 and NLRX1 at mitochondria, serving as a checkpoint of the RIGI-MAVS pathway, thereby inhibiting RLR-mediated type I interferon while promoting autophagy.
Hemoglobin and related oxygen transporters (Hemoglobin_oxygen_transport)
Type: Family

This family of proteins is involved in the transport of oxygen from respiratory organs to the rest of the body. They contain heme groups that reversibly bind oxygen molecules, facilitating their delivery to tissues that require oxygen for metabolism. Some members of this family also have roles in embryonic development, acting as embryonic hemoglobins. Additionally, certain variants within this family can bind to receptors such as the cannabinoid receptor CNR1, acting as antagonists and influencing signaling pathways related to pain and inflammation.
Prokaryotic/Mitochondrial Release Factor (Prokaryotic/Mito_RF)
Type: Family

The prokaryotic/mitochondrial release factor family is responsible for directing the termination of translation in response to peptide chain termination codons UAG and UAA. Members of this family play a crucial role in recognizing these stop codons during protein synthesis, ensuring that the translation process concludes accurately at the end of a gene's coding sequence. This function is vital for maintaining the fidelity of protein expression and preventing the synthesis of aberrant and potentially harmful proteins. The family includes both prokaryotic release factors and their mitochondrial counterparts, which are essential for normal cellular function and development.
Alanine--tRNA ligase (Ala-tRNA_ligase)
Type: Family

The Alanine--tRNA ligase family is responsible for the aminoacylation of tRNA(Ala) with alanine, a crucial step in translating genetic information into functional proteins. Members of this family activate alanine using ATP, forming Ala-AMP, which is then transferred to tRNA(Ala). The family also possesses an editing domain that ensures fidelity by removing incorrectly charged amino acids, such as serine or glycine, from tRNA(Ala). This proofreading function prevents the incorporation of incorrect amino acids into proteins, which is vital for maintaining the accuracy of protein synthesis. Some members of the family can also attach alanine to transfer-messenger RNA (tmRNA), aiding in the rescue of stalled ribosomes. The family is characterized by a modular domain architecture, typically including an N-terminal catalytic domain and an editing domain, with some variants also featuring a C-terminal C-Ala domain that can bind DNA and facilitate the cooperative interaction between the editing and aminoacylation centers.
ATP synthase B chain (ATP_synthase_B_chain)
Type: Family

The ATP synthase B chain family is involved in cellular energy production. Members of this family are components of the F(0) channel of ATP synthase, which is essential for ATP production from ADP using a proton or sodium gradient. The family includes various subunits that form the peripheral stalk, connecting the F(1) catalytic core to the F(0) membrane channel. Some variants, such as the b' subunit, are specific to plants and photosynthetic bacteria. These proteins are known for their stability, with some remaining functional after extended periods at high temperatures. In certain organisms, the enzyme may also act as an ATP-driven Na(+) pump, contributing to the generation of a sodium electrochemical gradient.
Phosphoglucosamine mutase (Phosphoglucosamine_mutase)
Type: Family

The phosphoglucosamine mutase family is involved in the biosynthesis of cell wall polysaccharides and peptidoglycan, crucial components for bacterial cell wall structure and integrity. Members of this family catalyze the interconversion of glucosamine-6-phosphate to glucosamine-1-phosphate, a precursor for UDP-N-acetylglucosamine (UDP-GlcNAc). UDP-GlcNAc serves as a substrate for various glycosyltransferases that synthesize cell wall components. The enzymatic activity of these proteins is essential for the proper formation of bacterial cell walls, which is vital for cell shape maintenance, protection against environmental stress, and regulation of cell growth and division.
Peptidoglycan biosynthesis MurCDEF (MurCDEF_pg_biosynth)
Type: Family

The MurCDEF family is involved in the synthesis of peptidoglycan, a critical component of bacterial cell walls that provides structural integrity and shape. Members of this family are enzymes that catalyze the addition of amino acids to UDP-N-acetylmuramate, a key step in the biosynthesis of peptidoglycan precursors. This process is essential for cell wall formation, which is vital for bacterial growth and survival. Some members of the family have bifunctional roles, also participating in the linkage of D-alanine residues in the peptidoglycan structure. The MurCDEF family includes enzymes such as UDP-N-acetylmuramate--L-alanine ligase, which specifically attaches L-alanine to UDP-N-acetylmuramate, and other related ligases that add further amino acids to the growing peptide chain. The activity of these enzymes is a target for antibiotic development, as inhibition can lead to weakened cell walls and lysis of the bacterial cell.
Proline-tRNA synthetase (Pro-tRNA_synthetase)
Type: Family

The protein family includes enzymes that catalyze the attachment of proline to tRNA(Pro) through a two-step reaction involving the activation of proline by ATP to form Pro-AMP, followed by its transfer to tRNA(Pro). Members of the family possess an editing function to ensure fidelity, hydrolyzing activated Ala-AMP and deacylating mischarged Ala-tRNA(Pro) to prevent errors. Some members can process cysteine but lack the ability to edit misacylated Cys-tRNA(Pro), which may be corrected by YbaK in trans. The family is characterized by a three-domain structure: a catalytic domain, an editing domain, and an anticodon-binding domain. These enzymes are essential for protein synthesis and are found in both cytoplasmic and mitochondrial locations, reflecting their importance in cellular function.
Universal ribosomal protein uL29 (Ribosomal_protein_uL29)
Type: Family

The universal ribosomal protein uL29 family consists of proteins that are components of the large ribosomal subunit. Members of this family are involved in the stabilization of the tertiary rRNA structure and are located at the polypeptide exit tunnel on the outside of the subunit. They play a role in the proper assembly and function of the ribosome, which is essential for protein synthesis. Some members of this family have been noted to interact with the 23S rRNA and may have additional regulatory functions related to ribosomal activity and protein translation.
Imidazole glycerol phosphate synthase HisA/HisF (IGPS_HisA/HisF)
Type: Family

The HisA/HisF family proteins are involved in the biosynthesis of histidine, an essential amino acid. The family includes imidazole glycerol phosphate synthase subunits HisF and HisH, which work together in a multi-enzyme complex. The HisF subunit is responsible for the cyclization activity, converting PRFAR (5'-phosphoribosylformimino-5-aminoimidazole-4-carboxamide ribonucleotide) into IGP (imidazole glycerol phosphate) and AICAR (5-aminoimidazole-4-carboxamide ribonucleotide), using ammonia provided by the HisH subunit. This reaction is a key step in the biosynthesis of histidine. The HisF subunit's activity is crucial for the production of histidine, which plays a significant role in the growth and development of organisms.
Bifunctional protein GlmU-like (GlmU-like)
Type: Family

This entry represents a family of prokaryotic proteins involved in the biosynthesis and recycling of bacterial cell wall components, such as Bifunctional protein GlmU, responsible for the formation of UDP-N-acetylglucosamine and N-acetylmuramate alpha-1-phosphate uridylyltransferase (MutU), which catalyses the formation of UDP-N-acetylmuramate , which are key precursors in peptidoglycan synthesis. Some family members play roles in peptidoglycan recycling, bypassing de novo synthesis pathways, contribute to intrinsic resistance to antibiotics like fosfomycin, and are involved in the synthesis of organic solutes in thermophilic microorganisms and the assembly of complex polysaccharides in bacterial surface structures.
UvrABC system protein C (UvrABC_protein_C)
Type: Family

The UvrC family proteins are involved in the nucleotide excision repair (NER) system, which identifies and processes DNA lesions. Members of this family, known as UvrABC system proteins, play a critical role in incising damaged DNA at both the 5' and 3' sides of the lesion. The N-terminal half of these proteins is responsible for the 3' incision, while the C-terminal half carries out the 5' incision. This dual incision mechanism is essential for the removal of the damaged DNA segment, allowing for subsequent repair synthesis. The UvrC family proteins, therefore, maintain genomic integrity by correcting DNA damage caused by various factors, including UV radiation and chemical mutagens. Their action is crucial for preventing mutations that could lead to cell malfunction or disease.
Isopropylmalate dehydratase and related enzymes (IPM_dehydratase_rel_enz)
Type: Family

The protein family is involved in the isomerization of specific tricarboxylic acids, playing a crucial role in various biosynthetic pathways. Members of this family catalyze the reversible isomerization between 2-isopropylmalate and 3-isopropylmalate through the intermediate formation of 2-isopropylmaleate. This reaction is a key step in the biosynthesis of leucine, an essential amino acid. Some family members also exhibit broad substrate specificity, catalyzing reactions involving cis-unsaturated tricarboxylic acids, including the dehydration of (R)-homocitrate to cis-homoaconitate and its hydration to homoisocitrate, which are part of the biosynthesis pathway of coenzyme B. The family includes enzymes like homoaconitase, which are involved in the alpha-aminoadipate pathway for lysine biosynthesis. The enzymes are characterized by their membership in the aconitase/IPM isomerase family and are found across a wide range of organisms, including bacteria, archaea, and eukaryotes.
UDP-N-acetylglucosamine 1-carboxyvinyltransferase MurA subfamily (MurA_subfamily)
Type: Family

The MurA subfamily of the EPSP synthase family is involved in bacterial cell wall biosynthesis. Members of this family are responsible for the addition of enolpyruvyl to UDP-N-acetylglucosamine, a critical step in the synthesis of peptidoglycan, which is a major component of the bacterial cell wall. This enzymatic activity is essential for cell growth and division, making it a target for antibiotics such as fosfomycin. The inhibition of MurA leads to the disruption of cell wall synthesis, which can result in bacterial cell death. The MurA subfamily is characterized by its conserved function across various bacterial species, reflecting its fundamental role in maintaining cell structure and integrity.
Urease subunit (Urease_subunit)
Type: Family

The urease subunit family is involved in the hydrolysis of urea into ammonia and carbon dioxide, a reaction that plays a crucial role in nitrogen metabolism. Ureases are nickel-dependent enzymes found in bacteria, fungi, and plants, and are important for survival in acidic environments, such as the stomach, by increasing local pH. In some pathogens, urease activity contributes to virulence by helping the organism colonize host tissues. The family includes alpha, beta, and gamma subunits, which assemble into a functional multimeric enzyme. Some members of this family may also be involved in defense mechanisms against phytopathogenic fungi and have entomotoxic activity.
Dehydroquinate Synthase (Dehydroquinate_synthase)
Type: Family

The Dehydroquinate Synthase family is involved in the shikimate pathway, which is essential for the biosynthesis of aromatic amino acids in bacteria, fungi, and plants. Members of this family catalyze the conversion of 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) to dehydroquinate (DHQ), a key step in the pathway. This reaction involves the cyclization of DAHP to form DHQ, which is then further processed to eventually lead to the production of aromatic compounds. The family is part of the larger sugar phosphate cyclases superfamily and does not include proteins with shikimate kinase activity, which may be present as a bifunctional enzyme in some species.
Peptidase M20A family, bacterial cell wall biosynthesis (Peptidase_M20A)
Type: Family

The peptidase M20A family includes enzymes that catalyze the hydrolysis of N-succinyl-L,L-diaminopimelic acid (SDAP) to form succinate and LL-2,6-diaminoheptanedioate (DAP), intermediates in bacterial biosynthesis of lysine and meso-diaminopimelic acid, essential components of bacterial cell walls. Some family members also hydrolyze the amide bond of N(2)-acetylated L-amino acids, releasing L-ornithine, an intermediate in L-arginine biosynthesis and polyamine synthesis. The family exhibits broad specificity, with some members able to deacetylate N-acetyl-L-citrulline, producing L-citrulline, or release L-lysine from [LysW]-gamma-L-lysine. The family's activity is regulated by metal ions and is inhibited by various compounds, including L,L-DAP and succinate.
2-IPM synthase/homocitrate synthase-like (2-IPM_HCS-like)
Type: Family

Members of the 2-IPM synthase/homocitrate synthase family are involved in the biosynthesis of essential amino acids, specifically leucine and lysine. They catalyse key condensation reactions in the respective biosynthetic pathways. The 2-isopropylmalate synthases catalyse the formation of 2-isopropylmalate from acetyl-CoA and 3-methyl-2-oxobutanoate, a crucial step in leucine biosynthesis. Homocitrate synthases, on the other hand, catalyse the condensation of 2-oxoglutarate with acetyl-CoA to yield homocitrate, initiating the alpha-aminoadipate pathway for lysine biosynthesis. Some family members also exhibit activity towards the formation of citramalate from pyruvate and acetyl-CoA. This entry also includes members of the 4-hydroxy 2-ketovalerate aldolase family (also known as 4-hydroxy-2-ketovalerate aldolase and 4-hydroxy-2-oxopentanoate aldolase (HOA)) that converts 4-hydroxy-2-oxopentanoate to acetaldehyde and pyruvate, the penultimate step in the meta-cleavage pathway for the degradation of phenols, cresols and catechol. The entry also includes enzymes with regulatory domains that are subject to feedback inhibition by the end products of the pathways, such as leucine and lysine, ensuring the balance of amino acid synthesis in the cell.
Dihydroorotate dehydrogenase (DHO_dehydrogenase)
Type: Family

The dihydroorotate dehydrogenase family is involved in the de novo pyrimidine biosynthesis pathway. Members of this family catalyze the stereospecific oxidation of (S)-dihydroorotate to orotate, a critical step in the production of UMP, which is a precursor for all other pyrimidine nucleotides. The enzymes within this family are classified into two subfamilies based on their electron acceptors: Type 1 subfamily members use NAD(+) as the electron acceptor, while Type 2 subfamily members utilize quinone. Some members can also use fumarate as an alternative electron acceptor. The activity of these enzymes is essential for the synthesis of pyrimidine nucleotides required for DNA and RNA production in organisms.
3-isopropylmalate dehydratase small subunit (LeuD)
Type: Family

The LeuD family proteins are involved in the isomerization of hydroxyacids as part of amino acid biosynthesis pathways. They catalyze the reversible isomerization between 2-isopropylmalate and 3-isopropylmalate via the intermediate 2-isopropylmaleate, a crucial step in leucine biosynthesis. Some members also display broader substrate specificity, functioning in the biosynthesis of coenzyme B by catalyzing the dehydration of (R)-homocitrate to cis-homoaconitate and its hydration to homoisocitrate. Additionally, they can hydrate maleate to (R)-malate and are involved in isoleucine biosynthesis by isomerizing 2-methylmalate and 3-methylmalate. This family plays a key role in central metabolic pathways and is essential for the production of important biomolecules.
Archaeosine Synthase Type 1/Queuine TRNA-Ribosyltransferase (ArchSynthase1/Queuine_TRR)
Type: Family

The Archaeosine Synthase Type 1 family is involved in the biosynthesis of archaeosine, a modified nucleoside found in the dihydrouridine loop of archaeal tRNA. Members catalyze the transformation of 7-cyano-7-deazaguanine (preQ0) in tRNA to archaeosine-tRNA, using glutamine, asparagine, or ammonium as amino donors. Additionally, they function in the base-exchange of guanine with the queuine precursor at the anticodon wobble position in tRNAs, facilitating the conversion to queuosine. This family also includes enzymes that add L-lysine to preQ0-modified tRNAs, forming a q0N lysine adduct. The enzymes can utilize guanine as a substrate and are implicated in virulence.
LexA repressor (LexA_repressor)
Type: Family

The LexA repressor family includes proteins that play a crucial role in bacterial DNA damage response, specifically the SOS response. Members of this family are responsible for repressing the transcription of genes involved in DNA repair and cell cycle regulation. Upon encountering single-stranded DNA, indicative of DNA damage, RecA protein interacts with LexA, triggering an autocatalytic cleavage. This cleavage disrupts LexA's DNA-binding ability, leading to the derepression of the SOS regulon and initiation of DNA repair processes. Some LexA proteins also bind to specific palindromic sequences in the DNA, further regulating the expression of SOS genes. This family is characterized by its involvement in maintaining cellular integrity and survival following DNA damage.
Ribosomal protein L11 methyltransferase PrmA (Ribosomal_L11_MeTrfase_PrmA)
Type: Family

The PrmA family of proteins functions as methyltransferases, specifically targeting the ribosomal protein L11. Members of this family are responsible for the post-translational methylation of L11, which is a critical modification for the proper function of the ribosome. The methylation process is believed to play a role in the accuracy of protein synthesis by the ribosome. The PrmA family is part of the larger methyltransferase superfamily, sharing common structural features that are characteristic of enzymes capable of transferring methyl groups to their substrates. One member, THET8 from Thermus thermophilus, is known to preferentially recognize and methylate free L11 before its incorporation into the 50S ribosomal subunit, a function that is dispensable for growth and thermostability.
DEAD box RNA helicase (DEAD_box_RNA_helicase)
Type: Family

The DEAD box helicase family is involved in various RNA metabolic processes including ribosome biogenesis, RNA degradation, mRNA splicing, and RNAi-mediated gene silencing. Members of this family are characterized by the presence of conserved motifs, including the Q motif, which controls ATP binding and hydrolysis. These proteins exhibit RNA-dependent ATPase activity and RNA unwinding activity, facilitating the remodeling of RNA structures and RNA-protein interactions. They are essential for the normal formation of ribosomal subunits and pre-rRNA processing, contributing to the assembly and stability of ribonucleoprotein complexes. Some subfamilies within this group are also implicated in cellular processes such as apoptosis, cell cycle progression, and response to stress, highlighting their diverse roles in RNA metabolism.
Ribonuclease PH (RNase_PH)
Type: Family

The RNase PH family comprises phosphorolytic 3'-5' exoribonucleases that are crucial for tRNA 3'-end maturation. They remove nucleotide residues following the 3'-CCA terminus of tRNAs and are capable of adding nucleotides to the ends of RNA molecules using nucleoside diphosphates as substrates. Although this addition activity may not be significant physiologically, it suggests a potential for reversible reaction. Members of this family are also implicated in the initiation of 16S rRNA degradation, which leads to ribosome degradation during starvation. This function is essential for maintaining proper cellular RNA levels and ensuring the fidelity of protein synthesis. The family includes both catalytic and non-catalytic components of the RNA exosome complex, which is involved in various cellular RNA processing and degradation events, including the maturation of stable RNA species, the elimination of RNA processing by-products, and the degradation of aberrant mRNAs.
Isoleucine--tRNA ligase (Ile-tRNA_ligase)
Type: Family

Isoleucine--tRNA ligase enzymes are responsible for the attachment of isoleucine to its corresponding tRNA molecule during protein synthesis. This process is crucial for the accurate translation of the genetic code into functional proteins. Isoleucine--tRNA ligases have two distinct active sites: one for aminoacylation and one for editing. The editing function is particularly important as it ensures the correct amino acid is attached to the tRNA, preventing errors that could result in dysfunctional proteins. The enzymes can inadvertently accommodate and process amino acids similar to isoleucine, such as valine. To avoid such errors, they possess two distinct tRNA(Ile)-dependent editing activities: 'pretransfer' editing, which involves the hydrolysis of activated Val-AMP, and 'posttransfer' editing, which involves the deacylation of mischarged Val-tRNA(Ile). These editing activities are essential for maintaining the fidelity of protein synthesis.
Ribosomal RNA large subunit methyltransferase RlmE (RNA_methyltr_RlmE)
Type: Family

The RNA methyltransferase RlmE family consists of enzymes that catalyze the methylation of the 2'-O position of the ribose in specific uridine residues within ribosomal RNA (rRNA). This methylation occurs at position 2552 of 23S rRNA in the fully assembled 50S ribosomal subunit, which is a universally conserved modification in the peptidyl transferase domain of the large subunit rRNA. The modification is critical for the proper assembly and function of the ribosome, which is essential for protein synthesis. Members of this family are S-adenosyl-L-methionine (SAM)-dependent methyltransferases and share a common SAM-binding motif. They are found across a wide range of organisms, including bacteria, archaea, and eukaryotes. The methylation reaction they catalyze plays a role in the accuracy and efficiency of protein synthesis, and thus, these enzymes are vital for maintaining the fidelity of genetic translation.
Membrane-localized HtpX protease (HtpX_protease)
Type: Family

The HtpX protease family is comprised of membrane-localized metalloproteases that play a role in the quality control of integral membrane proteins. Members of this family are capable of endoproteolytically degrading misfolded or overproduced membrane proteins, such as SecY, at specific cytoplasmic sites. These proteases do not require ATP for their activity, and their natural substrates are yet to be fully identified. The HtpX family is involved in the cellular process of protein turnover, particularly for the removal of damaged or non-functional membrane proteins, thereby maintaining cellular homeostasis.