SII-SWORD/CoKE huggingface dataset:
Peptidase S8/S53 subtilisin kexin sedolisin (Peptidase_S8/S53_subtilisin)
Type: Family

The peptidase S8 family encompasses a group of serine proteases with diverse functions, including broad substrate specificity, involvement in virulence as C5a peptidases that cleave human serum chemotaxin C5a, and roles in various cellular processes such as intracellular proteolysis, fruiting body formation, and swarming motility. Members of this family are characterized by their ability to hydrolyze proteins and peptide amides, with some showing resistance to harsh conditions and inhibitors. The family includes enzymes that are essential for the production of signaling factors and for developmental programs in response to environmental cues.
Dienelactone hydrolase-like enzyme (Dienelactone_hydrolase-like)
Type: Family

This family of proteins is involved in the ring cleavage of cyclic ester dienelactone to produce maleylacetate, a step in the degradation of certain compounds. Some members of this family have been identified as carboxymethylenebutenolidases, which are enzymes that catalyze the hydrolysis of dienelactone, a compound that can be found in various metabolic pathways including the breakdown of environmental pollutants. The family includes enzymes that may participate in the biodegradation of 5-nitroanthranilate by hydrolyzing lactones to produce maleylpyruvate. Members of this family share a similarity in sequence and structural characteristics, indicating a common evolutionary origin and similar catalytic mechanisms.
Lipid II flippase MurJ/MviN (Lipid_II_flippase_MurJ/MviN)
Type: Family

This family of proteins is involved in bacterial cell wall synthesis, specifically in the process of peptidoglycan biosynthesis. Members of this family function as transporters that facilitate the movement of lipid-linked peptidoglycan precursors across the cytoplasmic membrane from the inner to the outer leaflet. This translocation is a critical step in the construction of the peptidoglycan layer, which is essential for bacterial cell shape, rigidity, and protection against osmotic pressure. Some members of this family may also have additional regions with structural similarity to kinase-like domains and may be involved in regulatory interactions, although these domains are catalytically inactive.
E3 ubiquitin-protein ligase TRIM/RNF (E3_ubiq-ligase_TRIM/RNF)
Type: Family

This family of proteins includes E3 ubiquitin-protein ligases with a role in innate immune defense, particularly against viral infections . They mediate ubiquitination of key signalling molecules such as RIG-I and IFIH1/MDA5, which are crucial for the production of interferons in response to viral RNA . Some family members also regulate autophagy, inflammation, and cell survival pathways . They can ubiquitinate various substrates, influencing processes like mRNA stability, stress granule formation, and protein degradation. The family is characterised by the presence of a RING-type zinc finger domain, which is essential for their ligase activity, and some members have a B30.2/SPRY domain for substrate interaction. They are involved in modulating signal transduction pathways by ubiquitinating different proteins, thus affecting their stability and function.
Diverse substrate methyltransferase (Diverse_substrate_MTase)
Type: Family

This family of proteins includes enzymes with methyltransferase activity, which transfer methyl groups from S-adenosylmethionine to various substrates. Members of this family are involved in diverse biological processes, including the biosynthesis of secondary metabolites such as pigments, mycotoxins, and antibiotics, which have roles in microbial pigmentation, defense, and pathogenicity. Some proteins within this family are also implicated in modifying small molecules like trans-aconitate, potentially involved in metabolic regulation and response to nutrient availability. The proteins share a common structural framework typical of the methyltransferase superfamily, indicating a conserved mechanism of action across different biological contexts.
Enoyl-CoA hydratase/isomerase and chromodomain-containing protein (ECH/Chromodomain_protein)
Type: Family

This family of proteins includes enzymes involved in various metabolic processes, such as the isomerization of enoyl-CoA species and the dehalogenation of halobenzoyl-CoA compounds. Members of this family exhibit activities like hydratase, isomerase, and dehalogenase, playing roles in fatty acid metabolism, biosynthesis of host-selective toxins, and chromatin modification. Some proteins within this family are involved in epigenetic regulation by recognizing and binding specific histone modifications, influencing gene expression, DNA repair, and chromatin structure. Others are implicated in the biosynthesis of toxins affecting plant pathogens. The family also contains proteins with unclear or uncharacterized functions.
Bacterial SorC Transcriptional Regulators (SorC_transcr_regulators)
Type: Family

The SorC transcriptional regulatory family is comprised of proteins that function as transcriptional regulators with diverse roles in bacterial gene expression. Members of this family typically act as repressors or activators of operons in response to specific inducers or environmental conditions. For instance, LsrR proteins regulate the transcription of the lsr operon and their own transcription in the presence or absence of autoinducer 2 (AI-2), with AI-2 inactivation leading to operon transcription. Other family members, such as DeoR and EryD, control operons related to nucleoside and erythritol catabolism, respectively. The central glycolytic genes regulator (CggR) modulates the expression of glycolytic enzymes and is regulated by glucose availability. This family is characterized by a common DNA-binding domain and, in some cases, effector-binding domains that respond to specific ligands, indicating a versatile mechanism for controlling metabolic pathways and cellular responses to environmental changes.
PIF1 DNA helicase (PIF1_helicase)
Type: Family

The PIF1 helicase family is characterized by DNA-dependent ATPase and 5'-3' DNA helicase activities that are essential for maintaining mitochondrial and nuclear genome stability. Members of the family are adept at unwinding G-quadruplex (G4) DNA structures and forked RNA-DNA hybrids, which is crucial for preventing replication pausing and double-strand breaks at G4 motifs. The family plays a significant role in telomeric DNA maintenance by inhibiting telomere elongation and the action of telomerase, as well as resolving telomerase RNA/telomeric DNA hybrids. Some members are also involved in ribosomal DNA maintenance, Okazaki fragment processing, and may contribute to chromosomal replication. The PIF1 helicase family is found across a range of organisms, indicating a conserved function in genome integrity.
Glycosyl Hydrolase Family 73 (Glycosyl_Hydrolase_73)
Type: Family

The glycosyl hydrolase 73 family encompasses enzymes with diverse functions related to cell wall metabolism. Members of this family are involved in the endohydrolysis of the di-N-acetylchitobiosyl unit in high-mannose glycopeptides and glycoproteins, playing a crucial role in cell division by cleaving peptidoglycan and facilitating the separation of daughter cells. Some act as autolysins, contributing to cell lysis in the presence of penicillin. Others are specific muramidases that hydrolyze peptidoglycan during flagellum assembly or cell wall degradation, aiding in processes such as motility, chemotaxis, and cell division. The family also includes enzymes that hydrolyze 1,4-beta-linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan, influencing peptidoglycan structural determination during vegetative growth.
Phosphoinositide phospholipase C domain-containing protein (PI-PLC_domain)
Type: Family

This family of proteins includes enzymes with phospholipase C activity, specifically involved in the hydrolysis of glycosylphosphatidylinositol (GPI) and phosphatidylinositol (PI) anchors. These proteins do not cleave PI phosphates. Members of this family are implicated in various biological processes, including the release of soluble variant surface glycoproteins from the cell wall of parasites such as Trypanosoma brucei, potentially playing roles in parasite differentiation or antigenic variation. In some bacteria, these enzymes are considered potential virulence factors, possibly participating in the lysis of the phagolysosomal membrane and contributing to pathogenesis. The family encompasses a range of organisms, indicating a conserved function across different species.
GDSL Esterase/Lipase Enzyme (GDSL_Est/Lipase)
Type: Family

The GDSL lipolytic enzyme family is characterized by a broad range of esterase and lipase activities, acting on various substrates. Members of this family are involved in diverse biological processes, including lipid metabolism, cell signaling, and stress response. Some proteins within the family exhibit specific functions, such as hydrolyzing phospholipids, deacetylating xylo-oligomers, and contributing to salt tolerance and cellular homeostasis. The family is named after the conserved GDSL motif present in the active site of these enzymes. The motif contributes to their catalytic activity, which typically involves the hydrolysis of ester bonds in lipids and other molecules. The versatility of the GDSL enzymes is reflected in their wide distribution across different organisms and their involvement in various physiological functions.
Transcription factor verF-like (VerF-like)
Type: Family

This entry represents a group of fungal transcription factors that contain zinc finger domains, including Transcription factor verF from Penicillium polonicum . Members of this family are characterised by their ability to bind DNA and regulate the expression of target genes, which include those involved in metabolism, stress responses, developmental processes, and cell wall integrity. Some family members are involved in the regulation of specific metabolic pathways, such as nicotinate catabolism, while others play roles in the response to environmental stresses like oxidative stress or cell wall damage. Additionally, certain proteins within the family are key regulators of developmental transitions, such as hyphal growth in fungi, and are implicated in pathogenicity and virulence.
Carbamoyltransferase HypF-like (Carbamoyltrans_HypF-like)
Type: Family

This family of proteins includes enzymes involved in the maturation of [NiFe] hydrogenases, a class of enzymes that catalyze the reversible oxidation of hydrogen gas. Members of this family function as carbamoyl transferases, utilizing carbamoylphosphate as a substrate. They transfer the carboxamido moiety in an ATP-dependent reaction to specific cysteine residues of precursor proteins, facilitating the synthesis of CN ligands for the active site iron of [NiFe]-hydrogenases. Some members also exhibit carbamoyl-phosphate phosphatase activity in the absence of other substrates.
Zinc finger transcriptional regulators (Zinc_finger_trans_reg)
Type: Family

The Zinc finger protein family is characterized by its involvement in transcriptional regulation and ribosomal large subunit biogenesis. Members of the family interact with specific DNA or RNA regions to modulate gene expression. Some proteins within the family, such as Transcription factor IIIA, are essential for the transcription of 5S rRNA genes by RNA polymerase III and may also play a role in maintaining the transcription of other genes. They bind to internal control regions within these genes and the transcribed 5S RNAs. Other family members, like Zinc finger protein ZXDC and its homologs, cooperate with CIITA to promote transcription of MHC class I and II genes. Additionally, certain proteins act as transcriptional activators or repressors, influencing the expression of genes involved in pathways like trichothecene biosynthesis, mevalonate pathway, and various hormonal and metabolic processes. The family also includes proteins with E3 ubiquitin-protein ligase activity, contributing to cell proliferation and anti-apoptosis mechanisms.
DNA topoisomerase IB (Topoisomerase_IB)
Type: Family

The DNA topoisomerase IB family consists of enzymes that modulate the topological states of DNA by transiently breaking and rejoining one strand of the DNA duplex. They play a crucial role in releasing the supercoiling and torsional tension of DNA that arises during replication and transcription. These enzymes introduce a single-strand break via transesterification at specific target sites in duplex DNA. The catalytic tyrosine of the enzyme attacks the scissile phosphodiester, forming a DNA-(3'-phosphotyrosyl)-enzyme intermediate and releasing a 5'-OH DNA strand. The free DNA strand can then rotate around the unbroken strand, removing supercoils. Religation occurs when the DNA 5'-OH attacks the covalent intermediate, expelling the active-site tyrosine and restoring the DNA backbone. Some family members are involved in the regulation of alternative splicing, circadian transcription, and are essential for plant survival. They are also targets for specific inhibitors like camptothecin, which has antitumor properties.
Protein Disulfide Isomerase (PDI)
Type: Family

The protein disulfide isomerase family is involved in the formation, isomerization, and reduction or oxidation of disulfide bonds in proteins within the endoplasmic reticulum lumen. Members of this family act as protein-folding catalysts, interacting with nascent polypeptides to facilitate proper folding and stabilization through disulfide bond formation. Some family members have additional roles, such as involvement in glycosylation, prolyl hydroxylation, triglyceride transfer, and endoplasmic reticulum quality control. They may also be essential for various developmental processes, including pollen development, ovule fertilization, and embryo development. Certain proteins within this family possess thioredoxin activity and may engage in interactions with receptors to mediate cellular processes such as the phagocytosis of apoptotic cells.
SEC14-like and CRAL-TRIO domain-containing protein (SEC14/CRAL-TRIO_domain)
Type: Family

This family of proteins includes carriers and hydrophobic ligand-binding proteins that may be involved in various cellular processes, including innate immunity, vesicle trafficking, and cholesterol biosynthesis. Some members are known to negatively regulate the RIG-I signaling pathway, which is crucial for antiviral responses. They may also influence the transport and metabolism of hydrophobic molecules such as alpha-tocopherol, squalene, and phospholipids. Additionally, certain proteins within this family are implicated in tissue remodeling by promoting basement membrane mobility and gap formation.
Ras-related small GTPase (Ras-related_GTPase)
Type: Family

This family of proteins includes members that are part of the small GTPase superfamily, specifically within the Ras subfamily. These proteins are involved in various cellular processes through their ability to bind and hydrolyze GTP. They act as molecular switches that cycle between active GTP-bound and inactive GDP-bound states. Some family members are known to regulate rDNA transcription in cooperation with UBF/UBTF, positively influencing RNA polymerase I transcription. Others are implicated in growth regulation, with certain proteins showing a higher affinity for GDP over GTP, and possessing intrinsic GTPase activity. The family's role in growth regulation is highlighted by the influence of some members on cell proliferation, colony formation, and tumorigenic potential when overexpressed.
Transcriptional Regulator and Corepressor (Trans_reg/Corepressor)
Type: Family

This family of proteins includes transcriptional regulators and corepressors that are involved in the modulation of gene expression through chromatin remodeling. Members of this family are known to bind DNA and activate or repress transcription of specific target genes. They are involved in various biological processes, such as steroid biosynthesis, neuron-specific gene repression in non-neuronal cells, and the progression of meiosis in spermatocytes. Some proteins in this family function by interacting with other proteins to form complexes that modify histones through deacetylation and demethylation, thereby influencing chromatin structure and gene expression. They play roles in developmental processes, fertility, and hematopoietic differentiation.
Na+/H+ exchange regulatory cofactor (NHER)
Type: Family

The NHER family comprises scaffold proteins that regulate the surface expression and function of various membrane proteins, linking them to the actin cytoskeleton. They are involved in ion transport, second messenger cascades, and may enhance Wnt signaling. Some family members interact with regulatory components like NHERF1 to modulate membrane protein trafficking and activity. They play roles in multidrug resistance, chloride channel activity, cholesterol homeostasis, and renal tubule function. They are also involved in the regulation of phosphate reabsorption, sperm capacitation, and chloride and bicarbonate homeostasis in spermatozoa.
Major Facilitator Superfamily Domain-Containing Protein (MFS_Domain-Containing_Protein)
Type: Family

This family of proteins is part of the major facilitator superfamily (MFS), which is one of the largest groups of secondary transporters. Members of this family are involved in a variety of cellular processes, including the transport of small solutes across cell membranes. They function by utilizing chemiosmotic ion gradients. Some proteins within this family are known to act as outward-rectifying chloride channels that play a role in endolysosomal chloride homeostasis, membrane fusion, and function. They are involved in regulating lysosomal calcium content, pH in endolysosomal compartments, and may contribute to the progressive acidification from endosome to lysosome. The family includes proteins with SPX domains, which are indicative of their involvement in phosphate homeostasis.
Acetyl-CoA decarbonylase/synthase complex subunit (ACDS_complex_subunit)
Type: Family

The CdhD family is involved in the reversible cleavage of acetyl-CoA, which is a critical step in autotrophic growth from CO2 and growth on acetate as the sole source of carbon and energy. Members of the family are part of a larger acetyl-CoA decarbonylase/synthase (ACDS) complex, contributing to the complex's quaternary structure and function. Additionally, some family members act as methyl group carriers in the Wood-Ljungdahl pathway, which is an anaerobic process for carbon monoxide and carbon dioxide fixation. The family's role is pivotal in the metabolism of autotrophic organisms, facilitating the utilization of inorganic carbon sources and enabling energy production under anaerobic conditions.
NF-kappa-B Inhibitor (NF-kappa-B_inhibitor)
Type: Family

The NF-kappa-B inhibitor family consists of proteins that regulate the NF-kappa-B signaling pathway, which is crucial for immune and inflammatory responses. Family members inhibit NF-kappa-B activity by sequestering NF-kappa-B dimers in the cytoplasm, thus masking their nuclear localization signals. Upon cellular stimulation, these inhibitors are phosphorylated, leading to their ubiquitination and degradation, which allows NF-kappa-B to translocate to the nucleus and activate gene transcription. Some viral members of the family, derived from Polydnaviridae, have evolved to suppress the host immune response by binding NF-kappa-B without the regulatory regions necessary for dissociation and degradation, thereby preventing NF-kappa-B activation.
Leucine-rich repeat-containing bacterial E3 ubiquitin ligases (LRR-bact_E3_ubiq_ligases)
Type: Family

The LRR-containing bacterial E3 ligase family comprises effector E3 ubiquitin ligases that manipulate the host's ubiquitination pathway to promote bacterial survival within host tissues. These proteins typically exist in an autoinhibited state and are activated upon substrate binding. They are known to ubiquitinate various host proteins, leading to their proteasomal degradation, which interferes with host cell defense mechanisms such as the NF-kappa-B signaling pathway. Some family members specifically target host proteins like IKBKG, U2AF1, and guanylate-binding proteins, modulating inflammatory responses and suppressing host cell defenses. Others can ubiquitinate gasdermins or components of the LUBAC complex, impacting cell death pathways and innate immunity.
Voltage-dependent calcium channel gamma subunit (CACNG_subunit)
Type: Family

This family of proteins is involved in the regulation of ion channel trafficking and gating properties, particularly for AMPA-selective glutamate receptors (AMPARs) and L-type calcium channels. They play a role in promoting the targeting of AMPARs to the cell membrane and synapses, as well as modulating their activation, deactivation, and desensitization rates. Some members exhibit specificity for certain AMPAR subunits, while others regulate all subunits. Additionally, they are thought to stabilize calcium channels in a closed state, influencing neuronal excitability and synaptic plasticity.
ZNRF3/Arkadia E3 ubiquitin-protein ligases (ZNRF3_Arkadia_E3_ligases)
Type: Family

The ZNRF3/Arkadia protein family comprises E3 ubiquitin-protein ligases that play crucial roles in regulating the Wnt signaling pathway and the BMP-SMAD signaling axis. Members of the family mediate the ubiquitination and subsequent degradation of key components in these pathways, such as Wnt receptor complex components and SMAD inhibitors. This regulation is essential for processes like limb specification, mesoderm patterning during embryonic development, and maintaining the size of the intestinal stem cell zone. Some family members also bind polysumoylated substrates, enhancing transcriptional responses or promoting nucleotide excision repair. The activity of these ligases is modulated by their ability to bind ubiquitin non-covalently, which stabilizes the E2 enzyme in a closed conformation, facilitating ubiquitin transfer.
Sorting Nexin (Sorting_Nexin)
Type: Family

The Sorting Nexin family is involved in intracellular trafficking, endosomal sorting, and membrane protein retention. Members of this family play a role in the retention of late Golgi membrane proteins and are part of the retrieval machinery interacting with TGN membrane proteins. They bind phosphatidylinositol 3-phosphate (PtdIns(P3)) for localization and function. Some members are required for multivesicular body formation and endosome-to-TGN retrograde transport, facilitated by the retromer complex. They contribute to the stability and expression of various membrane proteins, including the epithelial sodium channel (ENAC). Additionally, they are involved in phagocytosis regulation, iron homeostasis through transferrin receptor recycling, and may influence neurite outgrowth. Certain members also play a role in the maturation of pathogen-containing vacuoles during infection.
SCF complex subunit WD repeat-containing protein (SCF_subunit_WD-repeat)
Type: Family

This family of proteins includes components of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complexes, which are involved in the ubiquitination and subsequent proteasomal degradation of target proteins. Members of this family are implicated in various cellular processes, including the regulation of sulfur metabolite repression by mediating the inactivation or degradation of specific transcription factors such as metR. They also play roles in cell cycle progression, sulfur metabolism, methionine biosynthesis, and the cellular response to cadmium. Some family members are involved in the regulation of autophagy by targeting ATG9 for degradation under normal conditions.