SII-SWORD/CoKE huggingface dataset:
Cation Diffusion Facilitator/SLC30A (CDF/SLC30A)
Type: Family

The Cation Diffusion Facilitator (CDF) family, also known as the SLC30A subfamily, comprises proteins that function primarily as metal ion transporters. These transporters are involved in the homeostasis of zinc and other divalent cations such as cadmium and cobalt. They mediate the efflux of zinc from the cytoplasm either into intracellular compartments like secretory vesicles, vacuoles, endosomes, and synaptic vesicles, or across the plasma membrane into the extracellular space or periplasm. This regulation of zinc ion concentration is crucial for various physiological processes including insulin secretion in pancreatic beta cells, zinc deposition in milk, and maintaining cellular zinc balance in the brain. Some family members also contribute to metal tolerance in plants and bacteria, providing resistance to high concentrations of metal ions by sequestering excess metals into vacuoles or by active efflux, thus reducing cytotoxicity and aiding in survival under metal stress conditions.
Bacterial molybdate/tungstate-binding (ModA/WtpA)
Type: Family

The ModA/WtpA protein family is involved in the transport of molybdenum and tungstate into bacterial cells. Members of this family are typically part of ABC transporter complexes, such as ModABC and WtpABC, which are binding-protein-dependent systems. These proteins exhibit high-affinity binding to molybdate and tungstate, and some can also bind chromate with lower affinity. The primary role of the ModA/WtpA family is to facilitate the uptake of essential trace elements like molybdenum, which is crucial for the function of various enzymes, including those involved in nitrate reduction. While the majority of the family members are characterized by their function in molybdate and tungstate transport, some proteins within this family remain uncharacterized, suggesting potential diversity in function.
Bacterial Polysaccharide Export ATP-binding (Bact_Polysacc_Export_ATP-bd)
Type: Family

The protein family is involved in the transport of polysaccharides across the cytoplasmic membrane. Members of the family are ATP-binding proteins that form part of ABC transporter complexes, which are responsible for the energy-dependent export of substances such as capsule polysaccharides, teichoic acids, O-antigens, and polysialic acid. These proteins are essential for the proper functioning of bacterial cell walls and capsules, contributing to the structural integrity and potentially to the virulence of various bacterial species by facilitating the export of critical components to the extracellular space.
HTH-type Transcriptional Regulators and Siroheme Decarboxylases (HTH-Siroheme_Decarb)
Type: Family

The protein family includes both transcriptional regulators and enzymes involved in heme biosynthesis. The transcriptional regulators are characterized by helix-turn-helix (HTH) motifs and are involved in various regulatory functions, including activation or repression of transcription and modulation of RNA polymerase recruitment. These regulators often control the expression of genes related to amino acid biosynthesis or their own transcription. The enzymes in the family, identified as part of the Ahb/Nir family, are involved in the decarboxylation of siroheme to didecarboxysiroheme, a key step in heme d1 and heme b biosynthesis. The activity of these enzymes can be modulated by the redox state of bound heme b and is stimulated by reducing agents like sodium dithionite.
Low-density lipoprotein receptor (LDLR)
Type: Family

The LDLR family is characterized by its role in mediating the endocytosis of lipoproteins, such as LDL and VLDL, into cells, which is crucial for cholesterol homeostasis and energy metabolism. Members of this family are multifunctional cell surface receptors that bind to various ligands, including cholesterol-carrying lipoproteins, and transport them into cells by clustering into clathrin-coated pits for internalization. Some members are involved in the oocyte-to-zygote transition and eggshell formation in certain species, while others participate in neuronal layering during embryonic brain development by transmitting extracellular signals to intracellular processes. Additionally, certain receptors within this family may act as tumor suppressors or be implicated in signal transduction and the uptake of lipophilic molecules. The family also includes receptors that play roles in immune responses and cobalamin uptake.
Dynein Intermediate Chain (Dynein_IC)
Type: Family

The dynein intermediate chain family is involved in the structure and function of dynein complexes, which are motor proteins that drive the movement of vesicles, organelles, and other cargos along microtubules. Members of the family play roles in linking dynein to these cargos and to adapter proteins, regulating dynein function. They are essential for intracellular retrograde motility, ciliary motility, and are involved in various cellular processes including ciliogenesis, cell migration, and mitosis. Some members act as negative regulators of signaling pathways and are involved in the assembly of the axonemal dynein complex, critical for respiratory cilia function and potentially in the regulation of cilia function more broadly.
Zinc finger and ubiquitin peptidase domain-containing protein (Zinc_finger/UBP_domain)
Type: Family

This family of proteins includes transcriptional regulators, deubiquitinases, and components of ribonucleoprotein complexes. They are involved in various cellular processes such as transcriptional regulation, chromatin remodeling, DNA damage response, and cell cycle progression. Some members function in the maintenance of telomeres, neuronal differentiation, and the regulation of gene expression during development. Others have roles in genome stability by interacting with ubiquitin chains and modulating the ubiquitination status of proteins involved in DNA replication and repair. Additionally, certain proteins in this family contribute to the repression or activation of neuronal genes in non-neuronal cells, influencing neural progenitor cell proliferation and differentiation.
FKBP-type Peptidyl-prolyl cis-trans Isomerase (FKBP-type_PPIase)
Type: Family

The FKBP-type PPIase family is characterised by its peptidyl-prolyl cis-trans isomerase activity, which accelerates the folding of proteins by catalysing the cis-trans isomerization of proline imidic peptide bonds in oligopeptides . Members of this family play a role in various cellular processes, including sexual development, TGF-beta receptor regulation , and modulation of calcium channel activity. They are also known for their interaction with immunosuppressive drugs, being inhibited by FK506 and rapamycin, which highlights their potential contribution to the pharmacological effects of these compounds.
JHDM1 Histone Demethylase (JHDM1_Histone_Demethylase)
Type: Family

The JHDM1 histone demethylase family is involved in the regulation of gene expression through the specific demethylation of histone lysine residues, which is central to the histone code. Members of this family demethylate various lysine positions on histone H3, such as 'Lys-4', 'Lys-9', 'Lys-27', 'Lys-36', and on histone H4 'Lys-20', with preferences for certain methylation states. These demethylases play key roles in processes such as brain development, cell cycle progression, transcriptional regulation, and maintenance of heterochromatin stability. Some family members also have non-histone substrates, influencing other cellular pathways. The family includes proteins with domains such as JmjC, PHD-type zinc fingers, CXXC zinc fingers, and F-box domains, which contribute to their demethylase activity, substrate specificity, and additional cellular functions.
Hyaluronan-binding Proteoglycan (Hyaluronan_bind_Proteoglycan)
Type: Family

The protein family is involved in the structural organization and stabilization of the extracellular matrix in various tissues, including cartilage and the central nervous system. Members of the family bind to hyaluronic acid, contributing to the formation of proteoglycan aggregates that resist compression in cartilage and facilitate neuronal conduction. Some family members modulate cell adhesion, motility, growth, and differentiation, and may also play roles in the formation of perineuronal nets and in the transmission of inhibitory synapses in the brain.
HTH-type transcriptional repressor FabR (HTH_transcr_repressor_FabR)
Type: Family

The HTH-type transcriptional repressor FabR family includes proteins that regulate the biosynthesis of unsaturated fatty acids (UFAs) by repressing the transcription of key genes such as fabB and fabA. These repressors are crucial for controlling UFA production, which in turn affects the physical properties of the cell membrane bilayer. Some family members have been suggested to require unsaturated acyl carrier proteins or unsaturated acyl-CoAs to bind DNA, while others may not need these molecules but use them to enhance DNA-binding affinity. The family plays a significant role in maintaining the fluidity and functionality of bacterial cell membranes by modulating the synthesis of UFAs.
Hsp70 Nucleotide Exchange Factors and Inhibitors (Hsp70_NEF-Inhibitors)
Type: Family

The FES1/SIL1 protein family includes nucleotide exchange factors (NEFs) that are essential for protein folding and translocation processes. Members of the FES1 subfamily function as NEFs for Hsp70 chaperones, accelerating the release of ADP and enhancing the efficiency of Hsp70-mediated protein folding. The SIL1 subfamily members are involved in protein translocation and folding within the endoplasmic reticulum, acting as NEFs for the ER lumenal chaperone HSPA5 or KAR2. Additionally, the family includes Hsp70-binding proteins that inhibit HSPA1A chaperone activity, affecting ATP binding and interfering with ubiquitination and chaperone-assisted degradation of proteins.
LRRC14/PRAME (LRRC14/PRAME)
Type: Family

This entry describes PRAME protein, Leucine-rich repeat-containing protein 14 (LRRC14) and related proteins.

Preferentially expressed antigen of melanoma (PRAME) was first isolated as a human melanoma antigen by cDNA expression cloning using melanoma-reactive cytotoxic Tcells (CTL). PRAME is a tumor associated antigen (TAA) of particular interest since it is widely expressed by lymphoid and myeloid malignancies and solid tumours, including melanomas, sarcomas, head and neck cancers, small-cell lung carcinomas and renal cell cancers. In normal tissues, PRAME expression has been reported in testis and low levels are found in endometrium, ovaries and adrenals . However, the PRAME gene is also expressed, although at a lower intensity, in CD34+ stem cells from healthy donors, which might constitute a problem for its application as a target in tumour immunotherapy . Epigenetic events represent the main mechanism regulating the expression of PRAME including DNA methylation of several promoter regions .
N-acetylmuramoyl-L-alanine amidase 3 (N-acetylmuramoyl_amidase_3)
Type: Family

The N-acetylmuramoyl-L-alanine amidase 3 family consists of cell-wall hydrolases involved in critical bacterial cellular processes. Members of this family play a role in septum cleavage during cell division, which is essential for bacterial proliferation and survival. Some proteins within the family also exhibit autolysin activity, contributing to cell-wall turnover and potentially participating in processes such as genetic transformation, flagella formation, and sporulation. The amidases hydrolyze the amide bond between N-acetylmuramic acid and L-alanine in peptidoglycan, a key component of the bacterial cell wall. This activity is crucial for cell-wall remodeling, maintenance, and during specific stages like germination and sporulation. The family includes proteins with broad-spectrum activity against various bacterial species, indicating a role in peptidoglycan fragment recycling. Regulatory mechanisms, such as autoregulation of the active site, are also observed in some family members.
Bacterial cell division protein FtsA/MreB (FtsA/MreB)
Type: Family

The FtsA/MreB family includes proteins that play a crucial role in bacterial cell division. Members of this family are involved in the assembly of the Z ring, which is essential for the cytokinesis process. These proteins may act as membrane anchors for the Z ring, facilitating the recruitment of other cell division proteins to the septal ring. They are also associated with ATP binding and hydrolysis, which suggests an active role in the conformational changes required during the cell division process. The extreme C-terminus of these proteins is particularly important for their localization, self-interaction, and activity.
Adenylyl/Guanylyl Cyclase Class-3/4 (Adenylyl/Guanylyl_Cyclase_3/4)
Type: Family

The adenylyl cyclase class-3/4/guanylyl cyclase family is involved in the synthesis of second messengers, cAMP or cGMP, from ATP or GTP respectively. These enzymes play essential roles in regulating cellular metabolism and responses to external signals. Some family members act as photoreceptors or potential receptors for unknown ligands, indicating a sensory function. The family includes pH-sensitive and photoactivated subtypes, and their activity can be modulated by various factors such as light, adenosine, GTP, and membrane potential changes.
RNA Processing Metallo-Beta-Lactamase (MBL)
Type: Family

This entry represents Metallo-Beta-Lactamase Domain (MLB) family. MLB proteins are involved RNA processing, particularly in the cleavage and polyadenylation of pre-mRNA, which is a critical step in mRNA maturation and stability. Members of this family are characterised by the presence of a MLB domain which is indicative of their role in RNA metabolism. Members of this family include endoribonuclease YSH1 found in bacteria, transcription termination factor FttA found in archaea and members of the cleavage factor I (CPSF3) and integrator complex suunit 11 (INT11) found in eukaryotes. They are involved in ranscription and processing of small nuclear RNAs (snRNAs), histone pre-mRNA processing, as well as in the biogenesis of microRNAs (miRNAs). They are essential for proper gene expression regulation and are linked to various cellular processes, including cell cycle progression .
RNA/DNA Helicase (RNA-DNA_Helicase)
Type: Family

The helicase family is involved in various aspects of RNA and DNA metabolism, including unwinding of duplexes, RNA surveillance, and processing of mitochondrial RNA. Members of this family play a crucial role in the degradation of RNA with a 3'-to-5' directionality in an ATP-dependent manner, often as part of larger complexes such as the mitochondrial degradosome (mtEXO), the nuclear exosome, and the SKI complex. They regulate the stability and removal of aberrant mRNAs, contribute to rRNA biogenesis, and are implicated in stress responses, DNA damage response, and recombination. Some members also have a role in antiviral defense and cellular stress tolerances, and are essential for embryogenesis, cell fate determination, and plasmodesmata development.
YIM1 and Zinc-containing Alcohol Dehydrogenase Families (YIM1/Zinc_Alcohol_DH_Fams)
Type: Family

The YIM1 family proteins are characterized by their similarity and shared nomenclature, indicating a potential common evolutionary origin or functional characteristics. The zinc-containing alcohol dehydrogenase family proteins, including the quinone oxidoreductase subfamily, are involved in various metabolic processes. These enzymes typically contain zinc and catalyze the reversible oxidation and reduction of alcohols and aldehydes. Some members of this family are implicated in the biosynthesis of pigments and antibiotics, playing roles in the formation of complex natural products with potential pharmacological applications. They may also be involved in cellular processes such as the regulation of neurite outgrowth and response to oxidative stress. The specific functions of individual proteins within these families can vary widely, reflecting the diverse roles that these enzymes play in different biological contexts.
Histone Modification Regulator (Histone_Mod_Regulator)
Type: Family

This family of proteins serves as scaffold subunits within various histone acetyltransferase (HAT) complexes, playing a crucial role in the regulation of gene expression through histone modification. Members of this family are involved in directing the specificity of HAT complexes towards particular lysine residues on histones H3 and H4, facilitating acetylation at these sites. This modification is key to the activation of replication origins and the transcriptional activation of genes throughout development. Some family members also possess histone methyltransferase activity, contributing to the epigenetic transcriptional activation by methylation of histone H3 lysine residues. Additionally, these proteins are implicated in several cellular processes including DNA replication initiation, apoptosis, tumor suppression, and the regulation of signaling pathways. The ubiquitin ligase activity of certain members further extends the family's role in protein post-translational modification and turnover.
Flavin Monoamine Oxidase (Flavin_MAO)
Type: Family

The flavin monoamine oxidase family is involved in the oxidative deamination of primary and secondary amines, including neurotransmitters and various xenobiotic substances. Members of this family play crucial roles in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. They catalyze reactions that typically result in the reduction of oxygen to hydrogen peroxide. Some family members have substrate specificity, such as preferentially oxidizing serotonin or degrading benzylamine and phenylethylamine. Others are involved in the degradation of nicotine or the biosynthesis of antibiotic compounds. The activity of these enzymes is regulated by various inhibitors and may involve metal cofactors alongside FAD. The family includes both well-characterized enzymes such as human MAO-A and MAO-B, as well as putative and uncharacterized proteins with predicted deaminase activity.
Peptidase C85-like (Peptidase_C85-like)
Type: Family

This entry represents human Deubiquitinase OTUD6B, OTU domain-containing protein 5 (OTUD5) and other C85 peptidases that contain the OTU domain (

). OTUD6B may play a role in the ubiquitin-dependent regulation of protein synthesis, downstream of mTORC1 . functions as a negative regulator of the innate immune system . This family also includes some viral sequences such as Putative ubiquitin thioesterase 232R from Invertebrate iridescent virus 3.
Cytochrome P450 3A (Cytochrome_P450_3A)
Type: Family

The Cytochrome P450 3A family comprises heme-thiolate monooxygenases involved in diverse oxidative metabolic processes. Members of the family are found in various organisms and are primarily located in liver microsomes. They play a crucial role in the metabolism of endogenous substrates such as steroids, fatty acids, and vitamins, as well as the biotransformation of xenobiotics, including drugs and environmental chemicals. The enzymes use an NADPH-dependent electron transport pathway to insert one oxygen atom from molecular oxygen into a substrate, while the other oxygen atom is reduced to water. Some family members are also implicated in olfaction, steroid hormone biosynthesis, and the metabolism of steroid hormones and retinoids during embryogenesis. The family's activities include hydroxylation of carbon-hydrogen bonds, oxidation of xenobiotics, and metabolism of steroid hormones and vitamins, contributing to homeostasis and detoxification processes.
Cyclic di-GMP phosphodiesterase-like (Cyclic-di-GMP_PDE-like)
Type: Family

This entry represents a group of bacterial Cyclic di-GMP phosphodiesterases, including PdeL from Escherichia coli . Members of this family are involved in the regulation of bacterial cellular processes through the hydrolysis of cyclic di-GMP (c-di-GMP), a second messenger that controls cell surface-associated traits such as motility, adhesion, and biofilm formation. These proteins possess phosphodiesterase (PDE) activity, catalysing the conversion of c-di-GMP to 5'-pGpG . Some members also serve as c-di-GMP sensors, coupling transcriptional activity to cellular c-di-GMP levels , or participate in signalling cascades affecting transcription factors and biofilm regulators . Others may have additional regulatory functions, such as modulating RNA stability or responding to environmental cues like oxygen availability and light.
HTH-type Transcriptional Regulators in Metabolic Pathways (HTH_MetabolicPath_Reg)
Type: Family

The protein family is composed of HTH-type transcriptional regulators involved in various metabolic and regulatory pathways across different bacterial species. Members of the family function as either activators or repressors of gene expression, often in response to specific metabolic cues. They regulate operons related to the utilization of compounds such as allantoin, glyoxylate, p-hydroxybenzoate, glycerol, 3-hydroxyphenylpropionate, and aromatic compounds. Some members control the expression of genes involved in catabolic pathways, such as the degradation of pectin, xylonate, and 2-keto-3-deoxygluconate, or the glyoxylate bypass operon. They typically act by binding to promoter regions of target genes or operons, modulating the transcriptional response to adapt to environmental changes or internal metabolic states. The binding and regulatory activity of these proteins can be influenced by specific inducers or co-repressors, such as glyoxylate, xylonate, or 1-hexanol, reflecting the dynamic nature of their regulatory roles in bacterial metabolism.
Type VI secretion system VgrG/RHS (T6SS_VgrG/RHS)
Type: Family

The VgrG/RHS protein family includes components of the type VI secretion system (T6SS) and cellular contact-dependent growth inhibition (CDI) systems. Members of this family are involved in interbacterial competition and virulence, delivering toxins into both prokaryotic and eukaryotic cells. Some act as structural spikes at the tip of T6SS, mediating the delivery of various effector proteins. Others possess enzymatic activities, such as actin cross-linking, ADP-ribosyltransferase, nuclease, and deaminase functions, disrupting cellular processes like the cytoskeleton, DNA integrity, and tRNA function. The family also includes RHS elements, which may have ecological roles in bacterial communities. These proteins often have a conserved N-terminal region and a divergent C-terminal domain, the latter often harboring the toxic activity neutralized by cognate immunity proteins. The VgrG/RHS family plays a crucial role in bacterial competition, mobility, biofilm formation, and insecticidal activity, with some members being secreted in response to environmental conditions.
Biotin Carboxyl Carrier/Decarboxylase Components (Biotin_Carboxyl_Carrier/Decarb)
Type: Family

This family of proteins includes biotin carboxyl carrier components and subunits of various carboxylase and decarboxylase enzyme complexes. They play a crucial role in carboxylation and decarboxylation reactions, which are essential for fatty acid synthesis and energy metabolism. These proteins typically undergo a two-step process where they are first carboxylated by a biotin carboxylase enzyme and then act as carriers to transfer the carboxyl group to specific substrates, forming products such as malonyl-CoA, oxaloacetate, or acetyl-CoA. Some members are also involved in the conversion of chemical energy from decarboxylation reactions into electrochemical gradients, such as sodium ion motive force for ATP synthesis.