SII-SWORD/CoKE huggingface dataset:
Ubiquitin-conjugating enzyme (Ub_conjugating_enzyme)
Type: Family

The ubiquitin-conjugating enzyme family is involved in the post-translational modification process known as ubiquitination, which tags proteins for various cellular processes. Members of this family accept ubiquitin from E1 activating enzymes and transfer it to target proteins, often with the help of E3 ligases. This modification can signal for protein degradation, alter protein function or localization, and affect protein-protein interactions. Ubiquitination plays a critical role in cell cycle regulation, DNA repair, signal transduction, and immune responses. Some family members also work with ubiquitin-like proteins such as NEDD8 and SUMO, expanding the functional repertoire to processes like nuclear architecture, chromosome segregation, and vesicle trafficking.
UPF0173/UPF0282/UlaG metal-dependent hydrolases (UPF0173_UPF0282_UlaG_hydrolase)
Type: Family

The UPF0173/UPF0282/UlaG protein family includes metal-dependent hydrolases and probable L-ascorbate-6-phosphate lactonases. Members of the UPF0173 and UPF0282 families are characterized by their metal-dependent hydrolase activity, although specific substrates and biological roles are not well-defined. Proteins belonging to the UlaG family are implicated in the utilization of L-ascorbate under anaerobic conditions, catalyzing the hydrolysis of L-ascorbate-6-phosphate into 3-keto-L-gulonate-6-phosphate. This activity is essential for L-ascorbate metabolism, highlighting the family's role in bacterial vitamin C utilization pathways. The diverse functions within this family reflect a range of enzymatic activities linked to metal ion coordination and hydrolysis, with implications for various metabolic processes.
Proteasome subunit alpha (Proteasome_alpha)
Type: Family

The proteasome subunit alpha family is involved in the ATP-dependent proteolytic degradation of most intracellular proteins. The proteasome is a multicatalytic proteinase complex essential for the regulated turnover of proteins and the removal of misfolded proteins. It cleaves peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The family includes both catalytic and non-catalytic components of the proteasome, with some members displaying chymotrypsin-like activity. The proteasome plays a key role in protein homeostasis, maintenance of cellular functions, and various pathways including spermatogenesis and generation of MHC class I-presented antigenic peptides. It is also involved in the degradation of ubiquitinated proteins and can mediate ubiquitin-independent protein degradation.
DNA polymerase type-Y (DNA_polymerase-Y)
Type: Family

The DNA polymerase type-Y family is characterized by poorly processive, error-prone DNA polymerases involved in untargeted mutagenesis and translesional synthesis. These enzymes copy undamaged DNA at stalled replication forks, which can occur due to mismatched or misaligned primer ends. They are capable of extending these misaligned primers without 3'-5' exonuclease (proofreading) activity, leading to increased rates of misincorporation and low processivity. The family plays a crucial role in DNA repair, particularly in situations where high-fidelity DNA polymerases are unable to proceed, allowing DNA synthesis to continue past lesions or damaged sites. This activity is essential for the survival and evolutionary fitness of organisms, as it provides flexibility in dealing with environmental stress and contributes to adaptive mutation during stationary-phase. Members of this family are also involved in UV protection and mutation, enhancing the organism's ability to cope with DNA damage caused by ultraviolet light.
Mitogen-activated protein (MAP) kinase (MAPK)
Type: Family

Mitogen-activated protein (MAP) kinases are integral components of kinase cascades, in which at least three protein kinases act sequentially to ultimately activate the MAP kinase itself . Activation occurs via dual phosphorylation on conserved threonine and tyrosine residues within a TXY motif. The MAP kinase family is involved in numerous cellular processes, including proliferation, differentiation, migration, transformation, and programmed cell death. These kinases are typically activated by a variety of extracellular stimuli, such as pro-inflammatory cytokines and physical stress. Once activated, MAP kinases phosphorylate a wide array of substrates, including transcription factors, cytoskeletal components, and regulators of apoptosis, translation, and other signalling pathways. They play a central role in signal transduction mechanisms, notably the MAPK/ERK cascade, influencing key cellular functions such as growth, adhesion, survival, and differentiation. In addition to their roles in transcriptional regulation, MAP kinases also participate in the modulation of endosomal dynamics, including lysosome processing, endosome cycling, and Golgi apparatus fragmentation during mitosis.
Purine/Pyrimidine Phosphoribosyltransferase (Pur/Pyrimidine_PRTase)
Type: Family

This family of proteins is involved in the purine salvage pathway, which recycles purines from nucleic acid breakdown back into nucleotide pools, reducing the need for de novo synthesis. Members of this family catalyze the transfer of a phosphoribosyl group to various purine bases, forming nucleoside monophosphates. Some proteins in this family may also act as repressors, regulating the transcription of genes involved in purine biosynthesis. The exact substrate specificity can vary among family members, with some preferring hypoxanthine or guanine, while others may act on xanthine.
C-C chemokine receptor type 1-9-like (CCR1-9-like)
Type: Family

This entry includes a group of G-protein coupled receptors characterized by its involvement in a wide range of physiological processes, including chemotaxis, immune response, inflammation, cell adhesion, and signal transduction. Among its members are C-C chemokine receptors type 1-9 receptors for various chemokines (including CCL3/MIP-1-alpha, CCL4/MIP-1-beta, RANTES, CXCL12/SDF-1), peptides, and other ligands, triggering intracellular signalling cascades that regulate cellular responses such as calcium ion flux, cell migration, proliferation, survival, and angiogenic activity . They play crucial roles in the cardiovascular system, central nervous system development, hematopoiesis, and in the regulation of blood pressure and sodium retention. Some receptors also function as coreceptors for viral entry, including HIV, and may be implicated in the development of AIDS dementia. This family includes both typical signaling receptors and atypical chemokine receptors that modulate immune responses by sequestering, degrading, or transcytosing chemokines.
Adenine phosphoribosyltransferase (Adenine_PRTase)
Type: Family

The adenine phosphoribosyltransferase family is responsible for a salvage reaction that converts adenine to AMP, a process that is energetically more efficient than de novo synthesis. Members of this family play a crucial role in recycling adenine into adenylate nucleotides. Some members also have the ability to inactivate cytokinins, plant hormones, by converting their free base form to corresponding nucleotides, thus regulating their activity.
Cytochrome P450 monooxygenase (Cytochrome_P450_monoxygenase)
Type: Family

Cytochrome P450 monooxygenases are a diverse family of enzymes involved in the oxidation of organic substances. They play a crucial role in the metabolism of drugs, the synthesis of cholesterol, steroids, and other lipids, and the detoxification of xenobiotics. These enzymes are also involved in the biosynthesis of various natural products, including mycotoxins, phytotoxins, antibiotics, and other secondary metabolites with applications in medicine and agriculture. They catalyse a wide range of chemical reactions, such as hydroxylation, epoxidation, dealkylation, and more, often using molecular oxygen and NADPH as substrates. Members of this entry are mainly found in bacteria and fungi.
Receptor Tyrosine Kinase (RTK)
Type: Family

The receptor tyrosine kinase family plays a crucial role in various cellular processes, including cell proliferation, differentiation, migration, and apoptosis. They act as cell-surface receptors for various ligands, such as fibroblast growth factors, insulin, and other growth factors, triggering intracellular signaling cascades that regulate embryonic development, the immune response, and the nervous system. Mutations or aberrant activation can lead to diseases like cancer. They are involved in angiogenesis, skeletal development, and maintaining vascular stability.
Prokaryotic molybdopterin-containing oxidoreductase (Prok_molybdopt-oxidoreductase)
Type: Family

The prokaryotic molybdopterin-containing oxidoreductase family includes enzymes that catalyze various redox reactions, often involving the transfer of electrons to or from quinones in the respiratory chain. Members of this family are involved in important metabolic processes such as nitrate reduction to nitrite, formate oxidation, and arsenic detoxification. They contain molybdopterin as a cofactor and may include additional metal centers like iron-sulfur clusters. These enzymes are typically found in the periplasmic space of bacteria and are integral to the anaerobic respiration pathway, allowing organisms to utilize alternative electron acceptors like nitrate when oxygen is scarce. Some members are also associated with the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) in eukaryotes, playing a critical role in electron transfer and energy conservation.
tRNA CCA-adding enzyme (tRNA_CCA-adding_enzyme)
Type: Family

The CCA-adding enzyme family is responsible for the synthesis and repair of the essential 3'-terminal CCA sequence in tRNAs. These enzymes operate without a nucleic acid template and sequentially add the nucleotides C, C, and A to the tRNA nucleotide-73, utilizing CTP and ATP as substrates and generating inorganic pyrophosphate. The 3'-terminal CCA addition is crucial for both tRNA processing and repair. Members of this family also play a role in tRNA surveillance, marking unstable tRNAs with a CCACCA sequence at the 3' terminus, which signals them for rapid degradation. Stable tRNAs, on the other hand, receive only the standard CCA sequence. The family includes multifunctional proteins that possess both nucleotidyltransferase activity in their N-terminal domain and phosphodiesterase and phosphatase activities in their C-terminal HD domain. These additional activities are involved in the hydrolysis of various nucleotide substrates and may contribute to the maintenance of tRNA integrity.
G-protein coupled receptor opsins (GPCR_opsins)
Type: Family

The opsins are a group of light-sensitive G-protein coupled receptors found in photoreceptor cells of the retina. Opsins bind to chromophores, such as retinal, and undergo a conformational change upon absorption of light, initiating a cascade of signaling events that ultimately contribute to visual perception. They are involved in various light-dependent physiological processes, including image-forming vision, pupillary reflex, and circadian photoentrainment. Opsins also play roles in non-image forming responses to light, such as the regulation of melanogenesis in melanocytes, and may influence metabolic processes in response to light exposure. The family includes opsins sensitive to different wavelengths, contributing to color vision and light intensity detection.
Diadenosine polyphosphate hydrolase (Ap4A_hydrolase)
Type: Family

This family of proteins is involved in the hydrolysis of diadenosine polyphosphates, specifically diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A), into adenosine diphosphate (ADP) or a combination of adenosine monophosphate (AMP) and adenosine triphosphate (ATP), depending on the enzyme's symmetry. Members of this family exhibit either symmetrical or asymmetrical hydrolysis activity. The symmetrical hydrolysis results in two ADP molecules, while the asymmetrical hydrolysis produces one AMP and one ATP molecule. These enzymes play a role in nucleotide metabolism and may be involved in the regulation of cellular processes that are sensitive to the levels of specific nucleotides.
Serine Proteases (Peptidase S1 Family) (Serine_Proteases_S1)
Type: Family

The peptidase S1 family, also known as the serine protease family, encompasses a diverse group of enzymes that share a common mechanism of proteolysis involving a serine residue in their active site. Members of this family are involved in a wide range of biological processes, including digestion, blood coagulation, fibrinolysis, immune response regulation, and cell migration. Notably, a subfamily within this group includes snake venom serine proteases, which often act in the hemostasis system of their prey, affecting blood coagulation and fibrinolysis. These enzymes typically cleave peptide bonds following arginine or lysine residues and are regulated by various inhibitors. Some members are also involved in the activation of other proteins, such as zymogens or factors in the coagulation cascade, and may have roles in tumor suppression, cell proliferation, and development.
Sulfate adenylyltransferase subunit 2 (Sulfate_adenylyltrnsfr_sub2)
Type: Family

The sulfate adenylyltransferase subunit 2 family is involved in the first enzymatic step of the sulfur assimilation pathway. Members of this family form a complex with CysN, known as ATP sulfurylase (ATPS), which catalyzes the adenylation of sulfate to produce adenosine 5'-phosphosulfate (APS) and diphosphate. The reaction is characterized by the formation of a high-energy phosphoric-sulfuric acid anhydride bond, which is driven by GTP hydrolysis by CysN and ATP hydrolysis by the CysD subunit. This process is crucial for the biosynthesis of sulfur-containing compounds, which are vital for various cellular functions.
Zinc-containing alcohol dehydrogenase (Zn_alcohol_dh)
Type: Family

The zinc-containing alcohol dehydrogenase family is characterized by its ability to catalyze the NAD(+)-dependent oxidation of various substrates. Members of this family are involved in diverse metabolic pathways, including the catabolism of sugars and amino acids. Key enzymes in this family include L-threonine 3-dehydrogenases, which oxidize L-threonine to 2-amino-3-ketobutyrate, and glucose 1-dehydrogenases, which oxidize D-glucose to D-gluconate. Other members have specific roles in the metabolism of compounds like D-arabitol, L-sorbose, and D-altritol. The family also contains enzymes like 2-deoxy-scyllo-inosamine dehydrogenase, involved in antibiotic biosynthesis. The broad substrate specificity and involvement in various metabolic processes make this family essential for cellular metabolism and adaptation to different nutritional environments.
ATP-dependent Clp protease/Chaperone ClpA/ClpB (ClpA_ClpB)
Type: Family

The ClpA/ClpB family proteins are molecular chaperones and ATP-dependent proteases that play crucial roles in stress responses, particularly in the recovery of cells from heat-induced damage. They are involved in the disaggregation, solubilization, and refolding of denatured protein aggregates, acting in cooperation with other chaperones such as DnaK, DnaJ, and GrpE. The ClpB chaperones have ATPase activity, which is stimulated by protein binding; the subsequent ATP hydrolysis unfolds the denatured protein aggregates. This unfolding exposes new hydrophobic binding sites on the surface of ClpB-bound aggregates, aiding in their solubilization and refolding by DnaK. The ClpA/ClpB family proteins contain nucleotide-binding domains responsible for ATP hydrolysis and oligomerization, and a coiled-coil domain essential for the rescue of proteins from an aggregated state. Some family members are also involved in the degradation of proteins by proteases like ClpP, regulation of genetic competence, and mitochondrial-mediated antiviral innate immunity.
Subtilisin-like serine protease (Peptidase_S8_subtilisin-like)
Type: Family

The peptidase S8 family, also known as the subtilisin-like protease family, consists of serine proteases that exhibit a broad range of functions, primarily associated with the proteolytic cleavage of various substrates. Members of this family are involved in diverse biological processes, including cholesterol homeostasis, protein degradation, nutrient acquisition, pathogenicity, and regulation of developmental processes. They are characterized by their ability to cleave after hydrophobic or small residues, often requiring Arg or Lys at the P4 position. The family includes enzymes that activate transcription factors through regulated intramembrane proteolysis, mediate lysosome biogenesis, contribute to virulence in pathogenic organisms, and regulate plasma cholesterol levels. The proteolytic activity of these enzymes is typically regulated by propeptides, metal ions, or specific inhibitors.
Glutamine/Glutamate--tRNA Ligase (Gln/Glu-tRNA_Ligase)
Type: Family

The Glutamine--tRNA and Glutamate--tRNA ligase family includes enzymes that play a crucial role in protein synthesis by catalyzing the attachment of amino acids to their corresponding tRNAs. Glutamine--tRNA ligases activate glutamine by ATP to form Glu-AMP and then transfer it to the acceptor end of tRNA(Gln), a process essential for translating the genetic code into proteins. Similarly, Glutamate--tRNA ligases perform the same function for glutamate and tRNA(Glu). These enzymes belong to the class-I aminoacyl-tRNA synthetase family and are vital for proper brain development in higher organisms. Some members of the family also participate in the biosynthesis of natural products in fungi.
Ion-translocating oxidoreductase complex subunit A/E (NqrDE/RnfAE_oxidrdctase)
Type: Family

The NqrDE/RnfAE family comprises membrane-bound complexes that couple electron transfer with ion translocation across the membrane. These complexes are involved in various cellular processes, including maintaining the reduced state of SoxR, nitrogen fixation, and energy conservation during autotrophic and heterotrophic growth. They catalyze the reduction of ubiquinone to ubiquinol, coupled with Na+ or H+ transport from the cytoplasm to the periplasm or out of the cell. This reaction is essential for various metabolic pathways, including methanogenesis from acetate. Some family members are specifically required for electron transfer to nitrogenase, which is crucial for nitrogen fixation. The activity of these complexes is tightly coupled to their ion pumping function and is essential for cellular energy metabolism and redox balance.
NAD-dependent sirtuin protein deacylases (NAD-dep_sirtuin_deacylases)
Type: Family

The sirtuin family of proteins are NAD-dependent deacylases that play crucial roles in various cellular processes, including DNA damage repair, telomere maintenance, metabolic homeostasis, inflammation, tumorigenesis, aging, and the regulation of circadian rhythms. They act by removing acetyl, malonyl, succinyl, and glutaryl groups from lysine residues on histones and other proteins, which modulates the activities of these proteins. Sirtuins contribute to chromatin silencing, cell cycle progression, genomic stability, and energy metabolism by deacetylating key transcription factors and coregulators. They serve as sensors of the cellular energy state and are involved in the response to metabolic and oxidative stress. Additionally, sirtuins regulate the expression of genes involved in apoptosis, autophagy, and lipid metabolism.
Deoxyguanosinetriphosphate triphosphohydrolase-like (dGTPase-like)
Type: Family

The dGTPase family is characterized by proteins that exhibit deoxyguanosinetriphosphate triphosphohydrolase activity, preferentially hydrolyzing dGTP over other canonical NTPs. This activity is crucial for maintaining the balance of deoxyribonucleotide triphosphates within the cell, which is essential for DNA replication and repair processes. The family includes several subfamilies, with proteins that may share similar structural domains but differ in regulatory mechanisms and specific functions. Some members act as host restriction factors, defending against viral infections by reducing cellular dNTP levels, thus inhibiting viral replication . Others are involved in DNA repair, promoting the resection of stalled replication forks independently of their dNTPase activity. The family also encompasses proteins that are allosterically regulated by GTP and dNTPs, forming active homotetramers upon binding these molecules.
Fatty acid oxidation complex subunit alpha (FA_oxidation_alpha_subunit)
Type: Family

The fatty acid oxidation complex subunit alpha family is involved in the aerobic and anaerobic degradation of long-chain fatty acids through the beta-oxidation cycle. Members of this family catalyze the formation of 3-oxoacyl-CoA from enoyl-CoA via L-3-hydroxyacyl-CoA, and can also use D-3-hydroxyacyl-CoA and cis-3-enoyl-CoA as substrates. Additionally, some members exhibit 3-hydroxyacyl-CoA epimerase and 3-hydroxyacyl-CoA dehydrogenase activities. The family includes mitochondrial trifunctional enzyme subunits that catalyze the last three reactions of the mitochondrial beta-oxidation pathway, which is a major energy-producing process breaking down fatty acids into acetyl-CoA. These subunits also have a monolysocardiolipin acyltransferase activity, acylating monolysocardiolipin into cardiolipin, a key mitochondrial membrane phospholipid.
PyrR bifunctional (PyrR_bifunctional)
Type: Family

The PyrR bifunctional protein family is involved in the regulation of the pyrimidine nucleotide (pyr) operon. Members of this family bind to specific sites on pyr mRNA in a uridine-dependent manner, which influences the formation of RNA secondary structures. This binding disrupts an antiterminator hairpin and promotes the formation of a downstream transcription terminator, leading to decreased expression of downstream genes. Additionally, these proteins exhibit a weak uracil phosphoribosyltransferase activity, although this function is not considered physiologically significant. The primary role of the PyrR family is to modulate the transcription of the pyr operon in response to the presence of exogenous pyrimidines, ensuring proper regulation of pyrimidine nucleotide synthesis.
Dihydroorotase/Allantoinase Hydrolase (DHOase/Allantoinase_Hydrolase)
Type: Family

The Dihydroorotase and Allantoinase protein family includes enzymes that catalyze distinct hydrolytic reactions in nucleotide and nitrogen metabolism. Dihydroorotases perform the reversible cyclization of carbamoyl aspartate to dihydroorotate, a key step in the de novo pyrimidine biosynthesis pathway. Allantoinases catalyze the hydrolytic cleavage of the five-member hydantoin ring of allantoin to allantoic acid, which is part of the purine catabolism pathway. Some members of the family are non-functional DHOases, while others are involved in the degradation of ureides without generating urea. The family belongs to the metallo-dependent hydrolases superfamily, with members distributed across various subfamilies based on their specific enzymatic functions.
Guanosine monophosphate reductase (GMP_reductase)
Type: Family

The GMP reductase family is involved in the purine-salvage pathway and plays a crucial role in nucleotide metabolism. Members of this family catalyze the irreversible NADPH-dependent deamination of GMP to IMP, thereby converting nucleotide derivatives of guanine to those of adenine. This enzymatic activity is essential for maintaining the intracellular balance of adenine and guanine nucleotides. The family includes proteins that may also contribute to the regulation of the purine nucleotide pool by recycling GMP to IMP. Some members are allosterically regulated by the ATP/GTP ratio and are inhibited by IMP and XMP, indicating a role in cellular nucleotide homeostasis. The family is also implicated in modulating cellular differentiation in higher organisms.