SII-SWORD/CoKE huggingface dataset:
Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
Type: Family

The Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) family includes enzymes that play a central role in the purine salvage pathway. Members of this family catalyze the transfer of the ribosyl-5-phosphate group from 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) to the N9 position of the 6-oxopurines hypoxanthine and guanine, resulting in the formation of the ribonucleotides inosine 5'-monophosphate (IMP) and guanosine 5'-monophosphate (GMP), respectively, with the concurrent release of pyrophosphate (PPi). Some family members also act on xanthine to produce xanthine monophosphate (XMP). These reactions are essential for recycling purines and contribute to the nucleotide pool necessary for DNA and RNA synthesis. The activity of these enzymes is critical for organisms that rely on purine salvage due to the absence of de novo purine synthesis pathways.
E3 ubiquitin-protein ligase (E3_ubiq-protein_ligase)
Type: Family

The protein family described is involved in the ubiquitination process, where members act as E3 ubiquitin-protein ligases. These enzymes accept ubiquitin from E2 ubiquitin-conjugating enzymes as thioesters and transfer them directly to target substrates. This post-translational modification can lead to various outcomes, including proteasomal degradation, altered cellular location, or changes in activity of the substrate proteins. The family members regulate diverse biological processes such as signal transduction, cell cycle progression, apoptosis, DNA repair, mRNA export, rRNA maturation, and immune responses. Some proteins within the family also have roles in regulating membrane dynamics, neuronal development, and autophagy. They are characterized by the presence of HECT, WW, or C2 domains, which mediate interactions with substrates and regulatory proteins, and are involved in autoinhibition and activation of the ligase activity.
CCR4/nocturin mRNA turnover and transcription (CCR4/nocturin_mRNA_transcr)
Type: Family

The CCR4/nocturin family is involved in various cellular processes related to mRNA turnover and general transcription regulation. Members of the family act as catalytic components of the CCR4-NOT core complex, which functions both in the nucleus as a general transcription factor and in the cytoplasm as the major mRNA deadenylase. The complex is linked to bulk mRNA degradation, miRNA-mediated repression, and translational repression during initiation. Some family members exhibit 3'-5' RNase activity with a preference for polyadenylated substrates and may also have low exonuclease activity towards single-stranded DNA. Additionally, certain proteins within the family play roles in pre-rRNA processing, circadian rhythm regulation, metabolic gene post-transcriptional control, and antiviral responses. The family's involvement in transcription and mRNA decay reflects its importance in gene expression regulation and cellular response to environmental cues.
Alpha-ketoglutarate-dependent hydroxylases (AlphaKG_dependent_hydroxylases)
Type: Family

The protein family includes alpha-ketoglutarate-dependent dioxygenases that catalyze hydroxylation reactions in various metabolic pathways. Members are involved in the degradation of lysine through a pathway that includes cadaverine and glutarate, converting glutarate to L-2-hydroxyglutarate. Other family members hydroxylate trimethyllysine to hydroxytrimethyllysine, a step in carnitine biosynthesis. Additionally, some enzymes contribute to antibiotic biosynthesis, such as clavaminate synthase, or participate in the synthesis of other specialized metabolites like hapalindole-type alkaloids. The family also includes enzymes that hydroxylate or oxidize unique substrates like tyrosine isonitrile, uridine-5'-phosphate, and enduracididine. These enzymes are characterized by their requirement for iron and alpha-ketoglutarate as co-substrates and are involved in diverse biological processes, including amino acid metabolism, secondary metabolite biosynthesis, and post-translational modifications.
Immunoglobulin-like Receptors in Immune Regulation (Ig-like_Receptors_ImmuneReg)
Type: Family

The protein family includes receptors that are predominantly expressed on the surface of immune cells, such as natural killer (NK) cells, T cells, B cells, and myeloid cells. Members of the family are involved in the regulation of the immune response through recognition of class I MHC antigens and other ligands. They play roles in inhibiting or activating cytolytic functions, modulating cytokine production, and contributing to immune tolerance and homeostasis. Some receptors possess immunoreceptor tyrosine-based inhibitor motifs (ITIMs) that recruit phosphatases to down-regulate cell activation, while others may lack inhibitory signals and instead activate immune responses. The family also includes receptors that participate in platelet adhesion and activation, osteoclast differentiation, and mast cell regulation. Collectively, these receptors are crucial for balancing immune protection against pathogens with the prevention of autoimmunity.
T cell receptor beta variable (TCR_beta_variable)
Type: Family

The T cell receptor beta variable family is composed of proteins that form part of the antigen-specific receptors on the surface of T lymphocytes. These receptors are crucial for the immune response, recognizing peptide-major histocompatibility complexes presented by antigen presenting cells. This interaction is essential for T cell adaptive immunity against pathogens. The family includes both functional and non-functional members, with the latter resulting from altered recombination or mutations. Upon antigen recognition, these receptors initiate a cascade of intracellular signaling pathways, leading to T cell activation, growth, and differentiation. The repertoire of these receptors is generated in the thymus and shaped by selection events to create a pool of self-restricted, non-autoaggressive T cells.
Fungal secreted metalloproteinases M35 (Fungal_M35_metalloproteases)
Type: Family

The peptidase M35 family comprises secreted metalloproteinases that are involved in the assimilation of proteinaceous substrates. They exhibit high activity on basic nuclear substrates, such as histones and protamines, which suggests a role in processing nuclear proteins. Members of the family are implicated in virulence, indicating a potential contribution to the pathogenicity of the organisms that produce them. The proteolytic activity of these enzymes is typically regulated by metal ions and can be inhibited by chelating agents, highlighting their dependence on metal cofactors for function.
Multicomponent Reductase Electron Transfer (MRET)
Type: Family

The protein family is involved in various electron transfer processes essential for the biodegradation of environmental pollutants and the metabolism of compounds such as cholesterol, aromatic compounds, and alkanes. Members of the family function as reductase components in multicomponent enzyme systems, transferring electrons from NAD(P)H to different oxygenase components. They play roles in the hydroxylation of phenolic compounds, degradation of steroids, and conversion of aliphatic compounds. Some members are also implicated in the luminescent systems of marine bacteria, supplying reduced flavin mononucleotide (FMNH2) for bioluminescence. The family includes proteins with iron-sulfur clusters and FAD-binding domains, indicating a diverse range of redox activities. They are characterized by their ability to interact with various substrates, including methane, toluene, phthalate, and others, highlighting their ecological importance in the breakdown of toxic environmental chemicals.
FAD-linked Oxidoreductases in Biosynthetic Pathways (FAD-linked_Oxidoreductase)
Type: Family

The FAD-linked oxidoreductase family encompasses enzymes that catalyse the oxidation of various substrates, often with the concomitant reduction of molecular oxygen to hydrogen peroxide. These enzymes are involved in a wide range of biosynthetic pathways, mediating the production of diverse bioactive compounds including indole diterpenes, sesquiterpene esters, polyketides, and mycotoxins . Members of the family are characterised by their dependence on flavin adenine dinucleotide (FAD) as a cofactor for their oxidoreductive activities. They play crucial roles in the formation of complex molecular structures, such as epoxides, lactones, and quinones, through mechanisms that may include hydroxylation, epoxidation, dehydrogenation, and cyclization. These enzymes are mainly from bacteria and fungi, and they contribute to the biosynthesis of natural products with potential pharmacological applications, including antitumor agents, immunosuppressants, and insecticides, as well as pigments responsible for fungal conidial coloration.
Sugar Epimerase/Isomerase (Sugar_Epim/Isomerase)
Type: Family

The protein family includes enzymes that catalyze the isomerization of various sugars, primarily involving the epimerization at the C3 position of ketopentoses and ketohexoses. Members of the family are involved in metabolic pathways such as the anaerobic utilization of L-ascorbate, myo-inositol degradation, and the biosynthesis of D-psicose. They exhibit broad substrate specificity, with some members showing activity towards L-ribulose, D-ribulose, D-allulose, D-fructose, L-xylulose, D-xylulose, D-tagatose, L-sorbose, D-sorbose, and hydroxypyruvate. The family also includes enzymes that catalyze the isomerization of 2-oxo-tetronate to 3-oxo-tetronate. Activity of these enzymes can be regulated by metal ions and EDTA. The family is characterized by a conserved structure, with some members having unique C-terminal alpha-helices that may influence oligomerization and stability.
D-isomer specific 2-hydroxyacid dehydrogenase, PdxB subfamily (D-iso_2-hydroxyacid_DH_PdxB)
Type: Family

The D-isomer specific 2-hydroxyacid dehydrogenase family, PdxB subfamily, consists of enzymes that primarily catalyze the oxidation of erythronate-4-phosphate to 3-hydroxy-2-oxo-4-phosphonooxybutanoate. This reaction is part of the vitamin B6 biosynthesis pathway. Members of this subfamily share a common structure with three discernible domains: the lid domain, the nucleotide-binding domain, and the C-terminal dimerization domain. The unique dimeric structure of these enzymes is attributed to the presence of the dimerization domain at the C-terminus. Some proteins within the broader D-isomer specific 2-hydroxyacid dehydrogenase family are involved in other metabolic processes, such as the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate in L-serine biosynthesis or the interconversion of hydroxypyruvate and glycerate in carbon assimilation.
Pentatricopeptide repeat-containing (PPR)
Type: Family

The PPR family proteins are characterized by their involvement in RNA editing within organelles such as chloroplasts and mitochondria. They act as site-recognition transacting factors essential for the conversion of specific RNA nucleotides, influencing the expression and function of organelle-encoded genes. These proteins play crucial roles in the biogenesis and maintenance of organelles, as well as in the regulation of photosynthetic electron transport chains by editing transcripts of subunits within the NAD(P)H dehydrogenase (NDH) complex and other components. The PPR family is also implicated in leaf vasculature patterning and chloroplast biogenesis.
Xaa-Pro aminopeptidase P (X-Pro_aminopeptidase_P)
Type: Family

The Xaa-Pro aminopeptidase P family comprises metalloaminopeptidases that catalyze the removal of penultimate prolyl residues from the N-termini of peptides. Members of this family are involved in the metabolism of various peptides, including the vasodilator bradykinin. They contribute to peptide degradation and may play roles in regulating physiological processes such as blood pressure. The family includes both soluble and membrane-bound enzymes, with some members being regulated by metal ions and inhibitors like apstatin and EDTA. The activity of these enzymes is essential in various organisms, from humans to plants and fungi, highlighting their fundamental role in peptide processing.
UPF0337 stress response protein (UPF0337_stress_rsp)
Type: Family

This family of proteins is characterized by membership in the UPF0337 (CsbD) family. The specific functions of these proteins are not well-defined, but they are generally thought to be involved in cellular stress responses. Members of this family may play a role in the general protection of the cell under stress conditions, such as extreme temperatures, desiccation, or the presence of toxic compounds. The exact mechanisms by which these proteins contribute to stress resistance, however, remain to be elucidated through further research.
Gfo/Idh/MocA family inositol dehydrogenases (Gfo-Idh-MocA_inositol_DH)
Type: Family

The Gfo/Idh/MocA family proteins are involved in the oxidation of myo-inositol (MI) to 2-keto-myo-inositol (2KMI or 2-inosose). Some members also catalyze the oxidation of D-chiro-inositol (DCI) to 1-keto-D-chiro-inositol (1KDCI). Additionally, certain enzymes within this family have been shown to act on other substrates such as D-glucose, D-xylose, and, to a lesser extent, D-ribose and D-fructose. The primary function of these enzymes is to participate in the inositol catabolic pathway, which is important for the metabolism of inositols, compounds that play a critical role in cellular signaling and membrane phospholipid synthesis.
NAD(P)-dependent dehydratase-like (NAD(P)_dehydrat-like)
Type: Family

This family of proteins includes enzymes that are primarily involved in various biosynthetic pathways, including the production of flavonoids , lignin , meroterpenoids , and other polyketide-derived compounds. Members of this family function as oxidoreductases, often utilising NAD(P)H as a cofactor to catalyse the reduction of ketones and aldehydes to secondary alcohols. They play crucial roles in plant defense mechanisms, the formation of pigments, and the regulation of plant hormone levels. Some family members are also involved in the detoxification of harmful compounds and the biosynthesis of steroidal hormones in animals .
Glycosyltransferase 28 (Glycosyltransferase_28)
Type: Family

The glycosyltransferase 28 family is involved in the transfer of sugar moieties from activated sugar donors to specific acceptor molecules, forming glycosidic bonds. Members of this family play key roles in various biological processes, including the biosynthesis of antibiotics such as anthracyclines, macrolides, and glycopeptide antibiotics, which are critical in cancer chemotherapy and as antimicrobial agents. They are also responsible for the glycosylation of sterols, forming sterol glucosides, which are important for cellular processes like autophagy and membrane stability. Some members exhibit broad substrate specificity, contributing to the detoxification of xenobiotics and the biosynthesis of complex natural products with potential pharmacological activities.
Human Olfactory Receptors (Olfactory_Receptors)
Type: Family

The olfactory receptor family is comprised of G-protein coupled receptors with the primary function of detecting odorants. These receptors are activated by a diverse array of chemical compounds, including organosulfur odorants with thioether groups, and in some cases, their activity is enhanced by copper binding. One member of the family also acts as a receptor for the hormone Asprosin, influencing glucose release from hepatocytes and regulating appetite and fertility. The activity of these receptors is typically mediated by G proteins that activate adenylyl cyclase, leading to an increase in intracellular cAMP levels.
Two-component system sensor histidine kinase (TCS_sensor_his_kinase)
Type: Family

The Two-component system sensor histidine kinase family is involved in a wide range of bacterial regulatory systems that respond to environmental stimuli. These proteins typically function as part of a two-component regulatory system, where they act as membrane-associated protein kinases. Upon sensing specific environmental signals, they undergo autophosphorylation on a histidine residue and subsequently transfer the phosphate to a response regulator protein, which then modulates the expression of target genes. These systems are involved in crucial bacterial processes including virulence, stress resistance, metal ion homeostasis, and adaptation to various environmental conditions such as low magnesium levels, acidic environments, and presence of antimicrobial peptides. Some family members also exhibit phosphatase activity, dephosphorylating the response regulator to modulate the signaling pathway. This dynamic regulation allows bacteria to rapidly adapt to changing conditions, contributing to their survival and pathogenicity.
Phosphotransferase System Glucose-Specific EIICBA (PTS_Glucose_EIICBA)
Type: Family

The Phosphotransferase System (PTS) Glucose-Specific EIICBA Family is involved in the active transport and phosphorylation of sugars across the cell membrane, primarily glucose, but also glucosamine, N-acetylglucosamine, and various alpha- and beta-glucosides. The system operates via a phosphoenolpyruvate-dependent mechanism, where the EIIA domain receives a phosphoryl group from phospho-HPr and transfers it to the EIIB domain. The EIIB domain, in turn, phosphorylates the sugar substrate during its translocation by the EIIC domain, which forms the translocation channel and contains the substrate-binding site. The phosphorylation of sugars is a critical step in their metabolism, and the PTS plays a significant role in regulating sugar uptake based on cellular needs and environmental availability.
Peptidase S1 family serine proteases (Peptidase_S1)
Type: Family

The peptidase S1 family is a diverse group of serine proteases with a variety of biological functions. Members of this family are involved in digestion, blood meal processing, and immune evasion. Some exhibit fibrinolytic activity, cleaving specific peptide bonds in fibrinogen, which can lead to anticoagulant effects. Others are involved in the establishment of parasitic infections by binding to host cells or transforming parasites into forms suitable for infection. Additionally, certain members act as secreted effectors in plant-pathogen interactions, targeting host endoglucanases to suppress plant defense responses. The family also includes enzymes that regulate insect development and reproduction, as well as allergens with protease activity.
Adaptor complexes medium subunit (Adaptor_comp_med_subunit)
Type: Family

The adaptor complexes medium subunit family is involved in the selection and concentration of membrane proteins into vesicles for intracellular trafficking. Members of this family are components of various adaptor protein (AP) complexes, such as AP-1, AP-2, AP-3, and AP-4, which are not always clathrin-associated. These complexes play roles in sorting proteins at the trans-Golgi network, endosomes, and plasma membrane, contributing to processes like endocytosis, vesicle formation, and cargo selection. Some family members are directly involved in recognizing tyrosine-based sorting signals on cargo proteins. The family also includes proteins like Stonin-1 and Stonin-2, which are implicated in the endocytic recycling of synaptic vesicles and may facilitate clathrin-coated vesicle uncoating.
FAD-linked Oxidoreductases in Biosynthesis Pathways (FAD-linked_Oxidoreductases_BP)
Type: Family

The FAD-linked oxidoreductase family is involved in various biosynthetic pathways across different organisms, catalyzing oxidation-reduction reactions. Members of this family play key roles in the biosynthesis of ergot alkaloids, cytokinins, mycotoxins, and other secondary metabolites. They are responsible for the transformation of specific substrates through redox reactions, often utilizing FAD as a cofactor. These enzymes are crucial for the production of compounds with pharmaceutical and agricultural significance, such as antimicrobial agents, plant hormones, and toxins. The family also includes enzymes involved in the biosynthesis of ascorbic acid and the epimerization of decaprenyl-phospho-ribose to decaprenyl-phospho-arabinose, a precursor for cell-wall arabinans in mycobacteria.
Myc family transcription factors (Myc_transcription_factors)
Type: Family

The Myc family of transcription factors plays a crucial role in cellular growth, proliferation, and apoptosis. Members of the Myc family bind DNA both non-specifically and specifically, recognizing the core sequence 5'-CAC[GA]TG-3'. They are involved in activating the transcription of growth-related genes and have roles in various cellular processes, including angiogenesis, stem cell self-renewal, and somatic reprogramming. Some family members, such as N-myc, are implicated in the positive regulation of transcription in neuroblastoma cells, while others like S-myc have apoptosis-inducing activity. The 9aaTAD motif, a common transactivation domain, is present in many Myc proteins, contributing to their function as transcription factors. Additionally, Myc proteins are involved in the regulation of alternative splicing of certain genes, influencing cellular metabolism and differentiation.
Glycosyl hydrolase family 28 (Glycosyl_hydrlase_28)
Type: Family

The glycosyl hydrolase 28 family is involved in the maceration and soft-rotting of plant tissue. Members of this family are enzymes that hydrolyze the 1,4-alpha glycosidic bonds of de-esterified pectate in the smooth region of the plant cell wall. These enzymes play a crucial role in the degradation of pectin, a major component of the plant cell wall. By breaking down pectin, they facilitate the penetration and spread of plant pathogens, contributing to disease progression in various plant hosts. The activity of glycosyl hydrolase 28 family members is essential for organisms that rely on the consumption or decay of plant material, making them important targets for the study of plant diseases and the development of agricultural biotechnology applications.
Mitochondrial Zinc Maintenance Protein 1 / LYRM7 (MZM1/LYRM7)
Type: Family

The MZM1/LYRM7 family includes mitochondrial proteins that function as assembly factors for the cytochrome b-c1 (CIII) complex, a component of the mitochondrial respiratory chain. Members of this family act as chaperones, binding to the Rieske Fe-S protein within the mitochondrial matrix. They stabilize the Rieske Fe-S protein, known as RIP1 in fungi or UQCRFS1 in animals, prior to its translocation and insertion into the late CIII dimeric intermediate within the mitochondrial inner membrane. Additionally, these proteins play a role in modulating the mitochondrial matrix zinc pool, which is crucial for various mitochondrial functions.
Iron-regulated surface determinant protein A (IsdA)
Type: Family

The IsdA family proteins are cell wall-anchored surface receptors involved in iron acquisition from host heme sources, crucial for the growth of bacteria like Staphylococcus aureus. They extract heme from oxidized methemoglobin and facilitate its transfer to other proteins in the heme uptake system. Additionally, IsdA family proteins play roles in immune evasion by protecting against host defense mechanisms such as bactericidal proteases, skin fatty acids, beta-defensins, and cathelicidin. They also bind fibronectin and fibrinogen, promoting bacterial clumping and colonization. The NEAT domain within these proteins is key for heme and fibrinogen binding, while also inhibiting apolactoferrin activity and conferring resistance to lactoferricin.