SII-SWORD/CoKE huggingface dataset:
ParA/MinD ATPase (ParA/MinD_ATPase)
Type: Family

The ParA/MinD family proteins are ATPases involved in various cellular processes, including the correct placement of division sites and the assembly of cellular structures. Members of the family, such as the septum site-determining protein MinD, play a crucial role in inhibiting premature formation of Z ring septums, thereby ensuring proper cell division. Some proteins within the family are also involved in the subcellular localization of biosynthesis apparatus, as seen in cellulose biosynthesis protein BcsQ, which is essential for cellulose production. Other family members, like the antiactivator FleN, regulate flagellar gene expression and maintain flagellar number. The family also includes proteins that regulate the placement and assembly of flagella, and proteins that may be involved in the insertion of nickel into carbon monoxide dehydrogenase. Overall, the ParA/MinD family is characterized by ATP-binding and hydrolysis activities that are central to their regulatory functions in cell division, biosynthesis, and motility.
Peptidase M16 (Peptidase_M16)
Type: Family

The peptidase M16 family comprises endopeptidases that play diverse roles in peptide processing and regulation. Members of this family are involved in the degradation of small peptides, such as glucagon and insulin, which is crucial for blood glucose homeostasis. Some members act as insulin-degrading enzymes, contributing to the cellular breakdown of insulin and other peptides, thereby regulating peptide hormone signaling cascades. The family also includes proteins involved in the biosynthesis of coenzyme pyrroloquinoline quinone (PQQ) by cleaving peptide bonds in a precursor peptide. Additionally, some members are implicated in the maturation of chloroplastic protein precursors by cleaving transit peptides, and others participate in the positive regulation of axonal maturation and myelination by activating ectodomain shedding of pro-neuregulin. The family's proteolytic activity is generally regulated by nucleotide triphosphates, small peptides, and inhibited by specific chelating agents and inhibitors.
Nitroreductase/BluB (Nitroreductase/BluB)
Type: Family

The Nitroreductase/BluB family includes enzymes that perform a variety of reduction and dehalogenation reactions. Members of this family are involved in the reduction of nitroaromatic compounds, often using NADH or NADPH as reducing equivalents, and in some cases, contributing to antibiotic resistance. A subset of the family, iodotyrosine deiodinases, play a crucial role in thyroid hormone biosynthesis by dehalogenating halotyrosines, facilitating iodide salvage. Another distinct subset, BluB enzymes, are involved in the biosynthesis of cobalamin (vitamin B12), catalyzing the oxidative fragmentation of FMNH2 to form 5,6-dimethylbenzimidazole. The family's diverse functions reflect its broad substrate specificity and involvement in various biological processes, including metabolism, detoxification, and hormone production.
SNF2/RAD54 Helicase and Transcription Factor (SNF2_RAD54_helicase_TF)
Type: Family

The SNF2/RAD54 helicase family is involved in various DNA processes, including transcriptional regulation, DNA repair, and chromatin remodeling. Members of the family function as helicases, often with ATPase activity, and are implicated in error-free postreplication DNA repair, particularly within the UBC2/RAD6 epistasis group. They are associated with the maintenance of genomic stability, acting on repetitive sequences and DNA double-strand breaks, favoring error-prone non-homologous joining. Some family members also possess ubiquitin ligase activity for 'Lys-63'-linked polyubiquitination of PCNA, contributing to DNA repair. Others are involved in transcriptional gene silencing and may influence nucleosome positioning. The family includes transcription termination factors that couple ATP hydrolysis with RNA polymerase II removal from DNA.
STE20/SPS1-related Proline-Alanine-rich Kinase (STE20/SPS1-PAK)
Type: Family

The STE20/SPS1-related proline-alanine-rich protein kinase family is involved in a variety of cellular processes including response to environmental stress, ion transport, cell polarity, growth, division, and apoptosis. Members of this family act as effector kinases in the WNK-SPAK/OSR1 kinase cascade, influencing ion cotransporter activity and contributing to the regulation of blood pressure and hypertonic stress response. They are also implicated in the regulation of cell migration, vesicle targeting, and fusion, as well as playing roles in developmental processes such as germ line development, spermatogenesis, and cytokinesis. Additionally, some members are involved in the JUN N-terminal pathway, acting upstream to mediate responses to stress stimuli.
WD repeat Echinoderm Microtubule-associated Protein-like (WD_repeat_EMAP)
Type: Family

The WD repeat EMAP family is involved in the regulation and modification of microtubule dynamics. Members of this family play crucial roles in the assembly, stability, and length of microtubules, affecting processes such as mitotic spindle organization, chromosome alignment during metaphase, and cell division orientation. Some proteins within this family are essential for normal brain development and neuronal progenitor cell proliferation. Others are implicated in ciliary and flagellar motility, contributing to spermatozoa motility and proper beating of cilia and flagella. The family includes proteins with a tandem atypical propeller in EMLs (TAPE) domain, which is characterized by a unique beta-propeller structure.
PheA/TfdB FAD monooxygenase (PheA/TfdB_FAD_monoxygenase)
Type: Family

The PheA/TfdB FAD monooxygenase family is involved in diverse hydroxylation reactions, primarily catalyzing the insertion of an oxygen atom into aromatic compounds. Members of this family are key enzymes in various biological pathways, including the degradation of phenolic compounds and the biosynthesis of antibiotics. They typically act on substrates such as 3-(3-hydroxyphenyl)propionate, hydroxycinnamic acid, and other aromatic molecules, facilitating the breakdown of these compounds into less complex forms that can be further metabolized. Some family members also participate in the modification of intermediate compounds in the production of antibiotics, enhancing their efficacy or altering their properties. The enzymes generally require FAD as a cofactor and exhibit higher catalytic efficiency with NADH over NADPH. The family's role in environmental detoxification and pharmaceutical biosynthesis highlights its importance in both ecological and medical contexts.
Neuropilin/Multicopper Oxidase/Coagulation Factor (Neuropilin_MCO_CoagFactor)
Type: Family

The protein family includes receptors involved in cardiovascular development, angiogenesis, neuronal circuit formation, and organogenesis. Members mediate chemorepulsant activity of semaphorins and bind to VEGF, initiating signaling pathways for motor neuron guidance and cell migration. Some family members are copper-binding glycoproteins with ferroxidase activity, playing roles in iron transport and antioxidant defense. Others are coagulation factors acting as critical cofactors in hemostasis. Additionally, the family includes proteins that contribute to phagocytic removal of apoptotic cells, mucosal healing, and VEGF-dependent neovascularization. They bind to phosphatidylserine-containing membranes and integrin receptors, influencing vascular morphogenesis and remodeling.
DNA Topoisomerase II (DNA_Topoisomerase_II)
Type: Family

The DNA topoisomerase II family consists of key decatenating enzymes that alter DNA topology to control its topological states. These enzymes function by transiently breaking and rejoining DNA strands, making double-strand breaks . They are essential for processes such as DNA supercoiling, mitosis, meiosis, and chromosome segregation. Some family members are involved in regulating transcriptional oscillation, B-cell differentiation, circadian rhythm, and chromatin insulator complex activity. They are also implicated in the resolution of centromeres during mitosis and the removal of cohesin from kinetochores. The family includes mitochondrial variants and is inhibited by certain intercalating agents.
Mitochondrial ATP synthase protein 8 (ATPase_protein_8)
Type: Family

The ATPase protein 8 family is involved in the production of ATP from ADP within the mitochondrial membrane. This process is driven by a proton gradient created by the respiratory chain's electron transport complexes. The family is part of the F-type ATPases, which have two domains: F(1), the extramembraneous catalytic core, and F(0), the membrane proton channel. These domains are connected by a central and a peripheral stalk. ATP synthesis at the F(1) domain is mechanically linked to proton translocation through a rotary action of the central stalk subunits. Members of the ATPase protein 8 family are minor subunits located within the F(0) domain, associated with subunit a in the membrane.
C2H2-type zinc finger domain-containing protein (C2H2-ZF_domain-containing)
Type: Family

This family of proteins includes transcriptional regulators with diverse roles in cellular processes such as transcriptional activation, repression, cell cycle progression, differentiation, apoptosis inhibition, and histone 3'-end pre-mRNA processing. Members of this family are characterized by the presence of C2H2-type zinc finger domains, which facilitate DNA binding and are often involved in interactions with other proteins and RNA complexes. These proteins are implicated in the regulation of gene expression by binding to specific DNA sequences and influencing the chromatin structure. Some members are involved in the epigenetic regulation and play critical roles in development, including oocyte and preimplantation embryo development, as well as X chromosome inactivation. The family also includes proteins that may act as tumor suppressors and participate in chromatin remodeling and sister chromatid cohesion.
NLRP family, innate immunity and inflammation regulators (NLRP_innate_immun_reg)
Type: Family

The NLRP family proteins are involved in innate immunity and inflammation. They act as sensors for pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), initiating the assembly of inflammasome complexes. These complexes activate pro-inflammatory caspases, leading to the maturation and secretion of cytokines IL1B and IL18, and inducing pyroptosis, an inflammatory form of cell death. Some family members regulate NF-kappaB signaling pathways, modulate actin dynamics in oocytes, and contribute to zygote division. Others have roles in redox homeostasis, Th2 cell differentiation, and tumor growth. The family includes proteins with diverse regulatory mechanisms, such as autoinhibition by ADP-binding, activation by various stimuli like ATP or pathogens, and interaction with other proteins through domains like LRR, PYD, and NACHT.
Amino Acid and Vitamin Transporters (AA-Vitamin_Transporters)
Type: Family

This family of proteins includes transporters that are primarily involved in the cellular uptake and efflux of various substrates, including amino acids, their metabolites, and vitamins such as riboflavin. Some members are known to transport S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), playing a role in the acquisition of SAM from host cells and the removal of the toxic by-product SAH. Others are implicated in the efflux of specific amino acids like threonine, homoserine, and cysteine, as well as in the response to cystine. The family also contains proteins that may function as export pumps for amino acid metabolites. These transporters are part of larger superfamily groups, including the EamA transporter family and the drug/metabolite transporter (DMT) superfamily.
Site-specific recombinase resolvase (SSR_resolvase)
Type: Family

The protein family includes site-specific recombinases known as resolvases, which perform crucial roles in DNA manipulation processes such as inversion and resolution of cointegrated replicons. These proteins are involved in the inversion of specific DNA segments, regulating gene expression and host specificity of viruses by altering the orientation of DNA fragments. They also catalyze the resolution of cointegrated replicons during transposition events, ensuring the proper segregation of genetic elements. The family's members share a common mechanism of action, introducing nicks into DNA, forming covalent intermediates, and executing strand exchange through a series of coordinated cleavage and religation steps. Their functions are vital for viral lifecycle, plasmid stability, and bacterial adaptability through phase variation and horizontal gene transfer.
Bacterial two-component sensor kinase systems (Bact_2-comp_sensor_kinase)
Type: Family

The LytS/LytT and HptS/HptR two-component regulatory systems, along with the nutrient-sensing BtsS/BtsR and YpdA/YpdB systems, form a network of sensor histidine kinases and response regulators that control various bacterial processes. These systems respond to environmental stimuli such as extracellular pyruvate, phosphate sources, and host defense peptides, regulating genes involved in cell wall metabolism, autolysis, programmed cell death, biofilm formation, hexose phosphate transport, and antibiotic susceptibility. The sensor kinases typically autophosphorylate a histidine residue and transfer the phosphate to a conserved aspartic acid in their corresponding response regulator, modulating its activity. Some also exhibit phosphatase activity, providing a mechanism for deactivation.
Rifampicin monooxygenase-like (RIFMO-like)
Type: Family

This entry represents a family of monooxygenases and aromatic-ring hydroxylases from eukaryotes and bacteria, including Rifampicin monooxygenase from Streptomyces venezuelae (RIFMO), which can modify rifampicin, thereby inactivating its antibiotic activity .

The rifampicin monooxygenases are characterised by its ability to modify and inactivate antibiotic compounds through monooxygenase activity. These enzymes are involved in the biosynthesis of various antibiotics, including polyketide antibiotics, and play a role in antibiotic resistance by modifying drugs such as rifampicin, thereby neutralizing their antimicrobial activity. This entry includes enzymes that catalyse hydroxylation reactions, often using FAD as a cofactor and NAD(P)H as an electron donor. These reactions are crucial in the biosynthetic pathways of anthracyclines, tetracyclines, and other aromatic polyketide antibiotics, contributing to their structural diversity and biological activity. Some family members are also involved in the degradation of environmental pollutants, such as pentachlorophenol, indicating a broader role in xenobiotic metabolism.
Pyruvate Dehydrogenase E1 Alpha Subunit (PDH_E1_Alpha_Subunit)
Type: Family

The Pyruvate Dehydrogenase E1 Alpha Subunit family includes enzymes that play a crucial role in cellular energy metabolism by catalyzing the conversion of pyruvate to acetyl-CoA and CO2. This reaction is a key step linking the glycolytic pathway to the tricarboxylic acid cycle. The family consists of multiple copies of three core enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2), and lipoamide dehydrogenase (E3). The E1 component is subject to regulation through phosphorylation, which inactivates the enzyme, and dephosphorylation, which reactivates it. This regulatory mechanism ensures precise control of the pyruvate dehydrogenase complex activity in response to cellular energy requirements.
Periplasmic Pilus Chaperone (Periplasmic_pilus_chap)
Type: Family

The Periplasmic Pilus Chaperone family consists of proteins involved in the biogenesis and assembly of various types of fimbriae and pili, which are filamentous structures on the surface of bacteria. These chaperones mediate the assembly of pili by forming soluble multimeric complexes with pilus subunits, protecting them from proteolytic degradation and preventing premature polymerization. The family members play a crucial role in bacterial adhesion to host cells and surfaces, contributing to colonization and virulence. They are part of different fimbrial operons and are essential for the proper assembly of fimbriae such as type 1, F1C, CS6, and others, which are involved in adherence to eukaryotic cells and may assist in microcolony formation.
Peptidoglycan Glycine Bridge Synthesis (PG_Glycine_Bridge_Synth)
Type: Family

This family of proteins is involved in the synthesis of bacterial cell wall peptidoglycan. Members of this family function as aminoacyltransferases that catalyze the addition of amino acids to the interpeptide bridge of peptidoglycan precursors. They utilize aminoacyl-tRNA as the amino acid donor in a ribosome-independent mechanism. Specifically, they are responsible for the formation of the pentaglycine bridge in Staphylococcus aureus, which is a key structural component of the cell wall. Different members add distinct glycine residues to the growing peptide chain, with some adding the first glycine to the lipid II intermediate, and others adding subsequent glycines. Their activity is crucial for cell wall integrity and is associated with resistance to antibiotics such as methicillin.
Histidine Acid Phosphatase (Histidine_acid_phosphatase)
Type: Family

The Histidine Acid Phosphatase family comprises enzymes with diverse functions including hydrolysis of phosphomonoesters, dephosphorylation of proteins, and regulation of glycosaminoglycan chain maturation. Members are involved in normal growth, development, and differentiation processes such as gut differentiation and odontogenesis. Some are implicated in the hydrolysis of lysophosphatidic acid, contributing to lipid metabolism, while others participate in the dephosphorylation of xylose in proteoglycan linkage regions, influencing glycosaminoglycan synthesis. Certain family members have roles in pain suppression, tumor suppression in prostate cancer, and even in the enhancement of viral infection. The family's enzymes are characterized by their activity under acidic conditions and are regulated by various factors including tartrate and cAMP.
CRISPR-associated endonuclease Cas1 (Cas1)
Type: Family

The CRISPR-associated endonuclease Cas1 family proteins are key components of the CRISPR adaptive immune system in bacteria and archaea, providing protection against mobile genetic elements such as viruses, transposable elements, and conjugative plasmids. Members of the Cas1 family are involved in the integration of spacer DNA into the CRISPR cassette. They act as dsDNA endonucleases and are essential for the transcription and processing of CRISPR clusters into CRISPR RNA (crRNA). Some family members also exhibit ssDNA exonuclease activity and are capable of binding to both ssDNA and dsDNA.
Plant LRR receptor-like serine/threonine-protein kinases (Plant_LRR-RLKs)
Type: Family

The LRR receptor-like serine/threonine-protein kinase family is involved in a wide range of plant physiological processes including growth, development, and immune responses. Members of this family function as receptors that perceive various extracellular signals, such as peptide hormones, brassinosteroids, and pathogen-associated molecular patterns, to regulate cellular processes. These kinases play key roles in meristem maintenance, vascular tissue development, thermotolerance, cell proliferation, and innate immunity. They are characterized by extracellular leucine-rich repeat domains that are essential for ligand binding and a serine/threonine kinase domain that transduces the signal through phosphorylation events. The family is also involved in the autoregulation of nodulation in legumes, controlling the number of root nodules formed based on nitrogen availability and previous rhizobial colonization.
F-box/Leucine-rich repeat (F-box_LRR-repeat)
Type: Family

The F-box/LRR-repeat protein family is involved in a variety of cellular processes, including cell cycle regulation, signal transduction, and protein degradation. Members of this family function as substrate-recognition components of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complexes, targeting specific proteins for ubiquitination and subsequent proteasomal degradation. This action is critical for maintaining cellular homeostasis and regulating biological processes such as cell division, development, and response to stress. The family also includes proteins that regulate ciliary/flagellar motility, iron homeostasis, and inflammation. Some members are involved in meiosis and ascospore formation, while others play roles in neural transmission and male fertility. The diversity of functions reflects the versatility of the F-box/LRR-repeat proteins in modulating various molecular pathways.
Paired Homeobox Transcription Factors (Paired_Homeobox_TFs)
Type: Family

The paired homeobox family of transcription factors is characterized by their involvement in a wide range of developmental processes across various tissues and organs. Members of this family play crucial roles in brain and spinal cord development, including neuronal proliferation, migration, differentiation, and axonal guidance. They are essential for the formation of sensory neuron projections, perception of pain, and the development of craniofacial structures, limbs, and skull. Some proteins within this family are involved in reproductive processes, spermatogenesis, and may regulate gene expression related to neurotransmitter pathways. Others contribute to the maintenance of specific cell phenotypes, such as noradrenergic neurons, and are implicated in processes like epithelial to mesenchymal transition (EMT) and cell cycle regulation during spermatogenesis. The family also includes proteins that regulate gene expression in the intestine and participate in vitamin A metabolism.
Type II Cytokine and Tissue Factor Receptors (Type-II_Cytokine-TF_Rcpt)
Type: Family

This family of proteins includes receptors that are part of the type II cytokine receptor family. They are involved in immune system processes, such as antiviral, antimicrobial, and antitumor responses, as well as blood coagulation. These receptors typically form heterodimeric complexes that bind various cytokines, including interferons and interleukins, which then activate signaling pathways like the JAK-STAT cascade. This leads to the phosphorylation and activation of transcription factors that regulate the expression of genes involved in the immune response and hemostasis. Some family members also play roles in anti-inflammatory functions, limiting tissue damage during inflammation, and may be involved in maintaining successful pregnancy.
Plant Cytochrome P450 Monooxygenase (Plant_Cytochrome_P450_Monoox)
Type: Family

The cytochrome P450 family is involved in diverse biosynthetic processes, including the metabolism of xenobiotics, fatty acids, and hormones, as well as the synthesis of defense compounds like glucosinolates, alkaloids, and phytoalexins. Members of this family function as monooxygenases, catalyzing the oxidation of organic substances using a heme iron-bound oxygen molecule. They play roles in the biosynthesis of natural products such as nicotine, sanguinarine, and noscapine, which serve as deterrents against herbivores and have pharmacological properties. Some members are involved in the hydroxylation of isoflavones and the conversion of indole glucosinolates, contributing to plant defense mechanisms against pests and pathogens. Others participate in the production of homoterpenes, attractants for herbivore predators, and in the formation of compounds like etoposide, used in chemotherapy.