SII-SWORD/CoKE huggingface dataset:
RISC Loading Complex Component (RLC_Component)
Type: Family

This family of proteins is involved in the RNA interference (RNAi) pathway and plays a critical role in the formation of the RNA-induced silencing complex (RISC). Members of this family are part of the RISC loading complex (RLC), which processes precursor microRNAs (pre-miRNAs) into mature miRNAs and loads them onto Argonaute proteins. These proteins also participate in the production of short interfering RNAs (siRNAs) from double-stranded RNA (dsRNA), which are key in post-transcriptional gene silencing. Additionally, they are implicated in the regulation of translation, either by repressing or altering the cleavage site of pre-miRNAs. Some members have a role in the innate immune response, particularly in viral infections, by interacting with and modulating the activity of proteins involved in interferon signaling.
UPF0507/Ankyrin repeat domain-containing protein 27 (UPF0507/Ank_repeat_27)
Type: Family

The UPF0507/Ankyrin repeat domain-containing protein 27 family is involved in various cellular processes including endosome dynamics, vesicle trafficking, and membrane fusion events. Members of the family may act as guanine exchange factors (GEFs) for Rab GTPases such as Rab21, Rab32, and Rab38, regulating their activity. They are implicated in the trafficking of melanogenic enzymes to melanosomes in melanocytes and may play a role in the distribution of peripheral melanosomes. Additionally, they are involved in neurite growth, potentially through GEF activity towards Rab21 and interactions with VAMP7, but not Rab32/38. The family may also participate in Golgi sorting of VAMP7 and its transport to the cell surface, as well as in GLUT1 trafficking from endosomes to the plasma membrane. The functions of the UPF0507/Ankyrin repeat domain-containing protein 27 family are essential for various cellular transport mechanisms and are associated with proteins such as VAMP7, kinesin heavy chain isoform 5, GOLGA4, RAB21, MACF1, and VPS29.
NLRP Inflammasome (NLRP_Inflammasome)
Type: Family

The NLRP inflammasome family plays a crucial role in innate immunity and inflammation. Members of this family act as cytosolic pattern recognition receptors (PRRs) that detect pathogen-associated signals, leading to the assembly of inflammasome complexes. These complexes recruit and activate caspase-1, which processes pro-inflammatory cytokines IL1B and IL18 and induces pyroptosis, a form of cell death. The family includes sensors that recognize specific pathogens or cellular stress signals, such as Bacillus anthracis lethal toxin or Val-boroPro inhibitor. Autoproteolytic processing within the FIIND domain is a common feature, generating N-terminal and C-terminal parts that associate non-covalently. The C-terminal part often oligomerizes to form the core of the inflammasome filament, with CARD domains playing a central role in caspase recruitment and activation. Regulatory mechanisms include ubiquitination and proteasomal degradation, modulated by DPP8 and DPP9 peptidases. The family's activity is also linked to host resistance to infection and regulation of NF-kappa-B signaling pathways.
Ser/Thr-Protein Kinase & FNIP Repeat-Containing Protein (STK_FNIP-Repeat)
Type: Family

This family of proteins includes serine/threonine-protein kinases and proteins containing FNIP repeats. The kinases are part of the protein kinase superfamily and the STE Ser/Thr protein kinase family, suggesting a role in phosphorylation of serine and threonine residues in substrate proteins, which is a common mechanism for regulating protein activity and signaling pathways. Some members are predicted to be catalytically inactive, implying a possible regulatory or scaffolding role rather than enzymatic activity. The FNIP repeat-containing proteins may be involved in protein-protein interactions, although their specific functions are not detailed in the provided annotations.
IS1 element transposase InsA (IS1_transposase_InsA)
Type: Family

This family of proteins is essential for the transposition of IS1 elements. Members of this family are involved in the mobility of these small genetic elements, which can move within a genome. Transposition is a key process by which these elements can cause mutations, rearrangements, or gene disruptions, contributing to genetic diversity, evolution, and in some cases, adaptation to new environments or antibiotic resistance. The proteins in this family share a common structure and function that facilitate the insertion or excision of IS1 elements from genomic DNA, thereby playing a crucial role in the dynamics of bacterial genomes.
11-beta-hydroxysteroid dehydrogenase (11-beta-HSD)
Type: Family

This family of proteins is involved in the regulation of glucocorticoid and mineralocorticoid levels by catalyzing the reversible conversion of inactive glucocorticoids to their active forms. They function predominantly as reductases in vivo, increasing the concentration of active glucocorticoids. These proteins play a crucial role in the corticosteroid receptor-mediated anti-inflammatory response, metabolic processes, and homeostasis. They exhibit broad substrate specificity, accepting various steroid and sterol substrates, and are involved in the metabolism of oxysterols, which are linked to apoptosis, atherosclerosis, and lipid peroxidation. Additionally, they contribute to bile acid metabolism and may influence immune cell migration through the synthesis of specific cholesterols that act as ligands for G-protein-coupled receptors.
Protein Phosphatase 1 Regulatory Subunit 15 (PPP1R15)
Type: Family

The PPP1R15 family proteins are involved in the regulation of protein synthesis and stress responses in cells. They recruit the serine/threonine-protein phosphatase PPP1CA to dephosphorylate EIF2S1/eIF-2A, reversing protein synthesis shutdown by stress kinases and aiding cell recovery from stress. They modulate the TGF-beta signaling pathway, potentially induce TP53 phosphorylation to promote apoptosis, and play a crucial role in autophagy by adjusting translation during starvation for lysosomal biogenesis and autophagic flux. Some family members act as viral restriction factors, attenuating replication of various viruses. Additionally, certain proteins in the family function as neurovirulence factors in viruses, mediating nuclear egress and inhibiting host immune responses, including the interferon response and the DNA sensing pathway.
Retroviral envelope glycoprotein (Retroviral_env_glycoprotein)
Type: Family

This family of proteins includes envelope glycoproteins from various retroviruses, including endogenous retroviruses (ERVs) and exogenous viruses like mouse mammary tumor virus (MMTV) and Jaagsiekte sheep retrovirus (JSRV). The primary functions involve receptor recognition and membrane fusion during viral entry into host cells. The surface unit (SU) of these proteins typically mediates binding to specific cell receptors, triggering conformational changes in the transmembrane unit (TM) that lead to membrane fusion and viral entry. Some members have evolved to lose their fusogenic properties, while others may have gained additional functions such as transformation of host cells or superantigenic properties. The proteins are characterized by a transmembrane domain that anchors the envelope heterodimer to the viral membrane and a fusion peptide domain that facilitates the merging of viral and cellular membranes.
Dictomallein (Dictomallein)
Type: Family

The Dictomallein family comprises proteins with a shared similarity, indicating a potential common functional or structural characteristic. However, the specific function of the Dictomallein family members, aside from the Metalloprotease StcE, is not detailed in the provided information. The Metalloprotease StcE is a virulence factor in enterohemorrhagic E. coli, contributing to intimate adherence to host cells, cleaving mucins and glycoproteins, and acting as an anti-inflammatory agent by localizing SERPING1 to cell membranes. It is inhibited by divalent cation chelators. The commonality in the family name suggests that other members may share related functions or structural properties, but without further information, a comprehensive description of the family's functions cannot be established.
Diverse Function CBS-Domain-Containing Protein (Diverse_CBS-Domain)
Type: Family

This family of proteins includes members with diverse functions, some of which are uncharacterized. A subset of proteins within this family are involved in the cellular response to hypoxia, but do not bind AMP, which is a common function of other CBS-domain containing proteins. Another subset is implicated in the metabolism of carbon sources such as acetoin or butanediol, playing a role in growth and sporulation. Additionally, one member is involved in homocysteine biosynthesis through the condensation of sulfide with aspartate semialdehyde, functioning independently of O-acetylhomoserine sulfhydrylase. The family also contains proteins that are currently uncharacterized, suggesting a potential for undiscovered functions or roles within the cell.
Diverse Substrate Transporter (Diverse_Substrate_Transporter)
Type: Family

This family of proteins includes transporters involved in the uptake and export of various substances across cellular membranes. Members of this family are characterized by their ability to transport a range of compounds, such as biotin and aromatic amino acids, including phenylalanine, tyrosine, and tryptophan. Some proteins in this family are implicated in conferring resistance to toxic compounds by facilitating their export out of the cell. The transport mechanism of these proteins may involve facilitated diffusion or active transport, and the structure of some family members includes a central substrate-binding cavity that accommodates a wide range of substrates.
Ribosomal RNA Methyltransferase (rRNA_Methyltransferase)
Type: Family

The RNA methyltransferase family is characterized by its members' ability to catalyze the methylation of ribose in various ribosomal RNA (rRNA) molecules, utilizing S-adenosyl-L-methionine (SAM) as the methyl donor. These enzymes are responsible for the post-transcriptional modification of rRNA, which is a conserved process essential for the proper function of the ribosome. The modifications typically occur at specific positions within the rRNA, contributing to the fine-tuning of ribosome structure and function, and in some cases, conferring resistance to certain antibiotics. Members of the family are part of the class IV-like SAM-binding methyltransferase superfamily and include both mitochondrial rRNA methyltransferases, which modify mitochondrial large subunit rRNA, and bacterial 23S rRNA methyltransferases, which target the bacterial large subunit rRNA and are associated with antibiotic resistance.
Diverse substrate monooxygenases (Diverse_substr_monoxygenases)
Type: Family

This family of proteins includes monooxygenases that catalyze diverse oxidative reactions, often involving the cleavage of carbon-sulfur bonds without breaking carbon-carbon bonds. Members are involved in various biological processes, such as the degradation of sulfur-containing compounds like dibenzothiophene-sulfone, the metabolism of nitrilotriacetate, and the conversion of long-chain alkanes into primary alcohols. Some enzymes in this family are also implicated in the biosynthesis of antibiotics, such as the oxidation of pristinamycin IIB to pristinamycin IIA. The family is characterized by a broad substrate specificity, with some members capable of acting on sulfides, sulfoxides, and sulfones, contributing to sulfur assimilation, detoxification, and environmental sulfur cycling.
NOD-like receptor (NLR)
Type: Family

The NOD-like receptor (NLR) family is involved in the innate immune response, acting as pattern recognition receptors (PRRs) that detect pathogen-associated molecular patterns (PAMPs) and danger danger associated molecular patterns (DAMPs) . Members of the family participate in various signalling pathways, including NF-kappa-B, MAP kinases, and type I/II interferon pathways, contributing to the transcriptional activation of genes involved in immune response, and play roles in gastrointestinal immunity, antiviral defence, autophagy, and inflammation regulation. Some NLRs detect specific bacterial peptidoglycan fragments, while others negatively regulate immune responses to prevent excessive inflammation. Proteins in this entry are implicated in metabolic regulation, appetite control, and cellular stress responses.
SMP-30/CGR1 Lactonase (SMP-30/CGR1_Lactonase)
Type: Family

The SMP-30/CGR1 family proteins are characterized by their lactonase activity, which plays a role in maintaining membrane homeostasis, particularly in cells with compromised membrane integrity. Some family members are known to contribute to bacitracin resistance and may act on various lactones, although their natural substrates remain unidentified. Additionally, certain proteins within this family can degrade organophosphorus compounds, including nerve agents, suggesting a broader substrate specificity. The activity of these enzymes is sensitive to chelating agents, indicating a possible dependence on metal ions for their lactonase function.
Cytochrome c-type biogenesis (C-type_cytochrome_biogenesis)
Type: Family

This family of proteins is involved in the biogenesis of c-type cytochromes, which are heme-containing proteins essential for electron transport and energy generation in the respiratory chain. Members of this family may function as subunits of a heme lyase complex, which is responsible for the attachment of heme to apocytochromes c. Additionally, some members are implicated in formate-dependent nitrite reduction, although they are not required for the biosynthesis or secretion of c-type cytochromes. The family includes proteins with varying degrees of involvement in these processes, reflecting a diversity of roles in bacterial respiratory and electron transfer systems.
FAD-binding Oxidoreductase/Transferase Type 4 (FAD-oxidored/transferase_4)
Type: Family

The FAD-binding oxidoreductase/transferase type 4 family is involved in the oxidation of various D-2-hydroxyacids, primarily catalyzing the conversion of D-2-hydroxyglutarate (D-2-HG) to alpha-ketoglutarate. Members of the family also oxidize other substrates such as D-malate and D-lactate, albeit with varying degrees of activity. The family plays a crucial role in cellular metabolism and energy production, as the reactions they catalyze are tied to the electron transport chain and are essential for the utilization of specific carbon sources. Some members are also implicated in the catabolism of amino acids like lysine, contributing to metabolic flexibility. The family includes enzymes that are activated by metal ions such as zinc and cobalt, and some are regulated by the concentration of these ions. The family is characterized by the presence of a flavin adenine dinucleotide (FAD)-binding domain and exhibits a broad taxonomic distribution, including members from bacteria to humans.
HIBADH-related NP60 subfamily (HIBADH-related_NP60_sf)
Type: Family

The HIBADH-related NP60 subfamily is involved in various biological processes, including chromatin modification, gene expression regulation, and oxidative stress tolerance. Members of this family act as nucleosome-destabilizing factors during transcriptional activation, recognizing and binding histone H3 and DNA without a preference for specific epigenetic markers. They interact with other proteins to form multifunctional enzyme complexes that facilitate Pol II transcription through nucleosomes. Some members may have oxidoreductase activity, although the active site is not conserved, suggesting a role as an oligomerization module. Additionally, certain members catalyze the NADPH-dependent reduction of glyoxylate and succinic semialdehyde, potentially playing a role in redox homeostasis and oxidative stress response.
Calcium-activated chloride channel regulator (CLCR)
Type: Family

The CLCR family includes proteins that are involved in mediating calcium-activated chloride conductance. Members of this family may play a role in various physiological processes such as goblet cell metaplasia, mucus hypersecretion, cystic fibrosis, airway hyperresponsiveness (AHR), and the regulation of tissue inflammation in the innate immune response. Some members are implicated in the regulation of mucus production and/or secretion by goblet cells and may act as tumor suppressors. The metalloprotease region of these proteins is responsible for autoproteolytic processing and may cross-cleave other CLCA substrates. Additionally, some members are involved in cell adhesion, potentially playing a role in the early stages of lung metastasis through interaction with integrins.
STEAP family metalloreductases (STEAP_metalloreductase)
Type: Family

The STEAP family proteins are integral membrane metalloreductases that function as NADPH-dependent ferric-chelate reductases. They facilitate the reduction of Fe(3+) to Fe(2+) across cellular membranes, using NADPH to transfer electrons through FAD and heme groups to the iron chelate. Some family members also reduce Cu(2+) to Cu(1+). These proteins play roles in iron uptake, particularly in erythroid cells, and are involved in systemic metabolic homeostasis, linking inflammatory responses with metabolic processes. They may influence cell cycle progression and apoptosis, and are implicated in conditions such as obesity, insulin resistance, and inflammatory arthritis. Certain STEAP proteins, despite belonging to the family, lack the necessary binding sites for NADPH and do not function as metalloreductases on their own.
Type I restriction enzyme R subunit (Type-I_R_enzyme_R_subunit)
Type: Family

This family of proteins includes the restriction (R) subunits of type I restriction enzymes. These enzymes are complex molecular machines that recognize specific DNA sequences, which are often asymmetric and contain non-methylated sites. Upon DNA binding, they translocate along the DNA in an ATP-dependent manner until a steric collision triggers cleavage at a distant, random site from the recognition sequence. The R subunit is essential for both the endonuclease and ATPase activities of the enzyme but is not involved in the modification of DNA. These proteins play a crucial role in bacterial defense mechanisms by cleaving foreign DNA, such as that from invading phages. The family members are characterized by their ability to induce conformational changes within the enzyme complex, regulating the balance between DNA methylation, cleavage, and translocation.
Iron-sulfur cluster electron transport (Fe-S_cluster_ET)
Type: Family

This family of proteins includes electron transporters that play a crucial role in various metabolic processes. Members of this family are primarily involved in transferring electrons through iron-sulfur clusters, acting as redox partners for different cytochrome P450 systems. They are essential components in the biosynthesis of diverse compounds, including antibiotics and sterols, by facilitating electron transfer to cytochrome enzymes involved in these pathways. The versatility of these proteins is evident in their ability to support a wide range of metabolic reactions across different organisms.
Tyrosine-tRNA ligase and regulatory protein (Tyrosine-tRNA_ligase_regulator)
Type: Family

This family of proteins includes enzymes that catalyze the ligation of tyrosine to tRNA(Tyr) in a two-step reaction involving the activation of tyrosine by ATP to form Tyr-AMP, followed by the transfer to the acceptor end of tRNA(Tyr). Members of this family also play a role in the regulation of poly-ADP-ribosylation in the nucleus, independent of their ligase activity. Binding of resveratrol modulates their activity, inhibiting the ligase function and promoting nuclear localization, where they enhance the poly-ADP-ribosyltransferase activity of PARP1. Additionally, some proteins in this family interact with tRNA as part of a multisynthase complex, influencing various cellular processes including inflammatory response, TGF-beta signaling, glucose homeostasis, wound repair, angiogenesis, and immune cell function.
Two-component system transcriptional regulators (2C-system_Tx_regulators)
Type: Family

The protein family is composed of transcriptional regulatory proteins that are part of two-component regulatory systems, which are typically involved in sensing environmental stimuli and regulating gene expression in response. Members of the family function as response regulators that, upon phosphorylation, bind to DNA and modulate the transcription of target genes. These proteins are essential for the expression of genes related to various cellular processes, including citrate-specific fermentation, plasmid inheritance, sporulation, and the anaerobic fumarate respiratory system. They may also be involved in the regulation of transporters and metabolic pathways in response to the presence of specific substrates such as C4-dicarboxylates and malate. The family includes proteins that can act as activators or repressors, and they often recognize specific DNA sequences to exert their regulatory functions.
RIO-type Ser/Thr kinase (RIO-type_Ser/Thr_kinase)
Type: Family

This family of proteins includes serine/threonine kinases predominantly involved in ribosomal biogenesis, particularly in the maturation of the 40S ribosomal subunit. They are implicated in the processing of pre-rRNA into mature 18S rRNA, and their catalytic activity is suggested to regulate their dynamic association with ribosomal subunits. Some members also play roles in cell cycle progression, chromosome stability, and mitotic segregation. Additionally, certain family members are involved in the immune response against viruses, acting as adapter proteins and modulating signaling pathways related to interferon response and apoptosis.
3'-5' Exoribonuclease (3-5_Exoribonuclease)
Type: Family

This family of proteins includes 3'-5' exoribonucleases involved in various RNA processing and degradation pathways. Members of this family play roles in the decay of histone mRNAs post-replication, suggesting a regulatory function in histone protein expression. They are capable of degrading RNA substrates with different structures, including stem-loop RNAs and short interfering RNAs (siRNAs), indicating a potential involvement in RNA interference (RNAi) mechanisms. Some family members are also implicated in rRNA biogenesis, specifically in the trimming of pre-5.8S rRNA. The activity of these proteins is regulated by interactions with other proteins and nucleic acids, and they exhibit a preference for RNA over DNA substrates. Their functions are essential for proper development, tissue formation, and cellular processes such as apoptosis and chromatin assembly.
Cellular adhesion and signaling domain-containing protein (Cell_adhesion_signaling)
Type: Family

This family of proteins is involved in various cellular adhesion processes, including synaptic adhesion and the formation of specialized cell-cell junctions. Members of this family play crucial roles in the development and function of the kidney glomerular filtration barrier, as well as in the maintenance of podocyte architecture. They are also implicated in the regulation of vascular permeability and the anchoring of the podocyte slit diaphragm to the cytoskeleton. Some family members are necessary for synapse formation in the nervous system, acting as homophilic adhesion molecules that promote trans-cellular interactions and stabilize synaptic structures. Additionally, certain proteins within this family may have a role in supporting hematopoietic stem cells and regulating insulin secretion.