SII-SWORD/CoKE huggingface dataset:
Integrator complex subunit 12 (Integrator_subunit_12)
Type: Family

This family of proteins is involved in the transcription and 3'-box-dependent processing of small nuclear RNAs (snRNAs), including U1 and U2, which are essential for pre-mRNA splicing. Members of this family are components of the Integrator complex, which associates with the C-terminal domain (CTD) of RNA polymerase II's largest subunit (POLR2A) and is recruited to snRNA genes. Additionally, these proteins are implicated in the recruitment of cytoplasmic dynein to the nuclear envelope, suggesting a role in intracellular transport processes.
Insulin-like_neuropeptide_ligands (Insulin-like_neuro_ligands)
Type: Family

This family of proteins includes members that are involved in various signaling processes. Some proteins within this family are known to act as ligands for specific G protein-coupled receptors, such as LGR7, RXFP3, and RXFP4. These interactions suggest roles in neuropeptide signaling and potentially influence physiological functions such as gut contractility, thymic development, and regulation. The family is characterized by structural similarity to the insulin family, indicating a possible evolutionary relationship and functional resemblance to insulin in terms of peptide hormone action.
KH Domain-Containing Protein 1 (KHDC1)
Type: Family

The KHDC1 family proteins play a crucial role in DNA replication and repair, particularly in oocytes and early embryonic development. They form the OOEP-KHDC3 scaffold, which is essential for recruiting BLM and TRIM25 to DNA replication forks, promoting BLM ubiquitination and retention, thus aiding in the restart of stalled replication forks. They also regulate the homologous recombination-mediated DNA double-strand break repair pathway by controlling ATM activation and RAD51 recruitment to breaks, contributing to oocyte survival and meiotic progression. As part of the subcortical maternal complex, they are vital for zygotic cell division regulation, actin dynamics, and mitotic spindle formation and positioning. This ensures symmetric division and euploidy during early embryogenesis. Additionally, they influence neural stem cell neurogenesis, neuronal differentiation, and may affect learning, memory, and anxiety development.
Small heat shock protein hspG1-11-like (HspG1-11-like)
Type: Family

This family of proteins is found in amoeboid protists and is characterised by their role in cellular stress response. There proteins are part of the HSP20 proteins superfamily, including hspG1-11 from Dictyostelium discoideum. Members of this family function as molecular chaperones that can prevent the aggregation of misfolded proteins, thereby protecting cells from stress-induced damage. They are typically activated by heat shock and other environmental stress conditions. These proteins are known to bind to partially unfolded proteins, facilitating proper folding or refolding, and can also participate in protein transport and cellular signaling pathways. Their ability to interact with a wide range of substrate proteins makes them crucial for maintaining cellular proteostasis, especially under conditions that can lead to protein denaturation and aggregation.
Calcium Up-regulated Membrane Regulator (Ca_Up-reg_Membrane_Reg)
Type: Family

This family of proteins may be involved in the stabilization and regulation of the cell membrane in response to calcium stress or during certain developmental stages. Members of this family are characterized by their potential role in cellular responses to changes in calcium concentration, which suggests a function related to maintaining cellular integrity and signaling under specific conditions.
Metallo-dependent Hydrolase Enzymes (Metallo-dep_Hydrolase)
Type: Family

This family of proteins includes enzymes that are part of the metallo-dependent hydrolases superfamily. Members of this family exhibit a range of hydrolytic activities, often involving the cleavage of specific chemical bonds in substrates. Some proteins within this family function as carboxypeptidases, releasing C-terminal amino acids with a preference for aromatic residues, such as phenylalanine. These enzymes are capable of degrading ochratoxin A, a harmful mycotoxin found in various agricultural products. The structure of these proteins typically features a two-domain architecture with a TIM-barrel and a beta-sandwich domain. Activity of some family members is known to be inhibited by Zn(2+)-specific chelators. Other proteins in the family are involved in distinct hydrolytic reactions, such as the hydrolysis of alpha-D-ribose 1-methylphosphonate triphosphate.
ABC Transporter Superfamily, Various Functions (ABC_Transporter_VariousFunc)
Type: Family

The ABC transporter superfamily is a diverse group of proteins that utilize ATP hydrolysis to translocate a wide variety of substrates across cellular membranes. Members of this family are involved in various biological processes, including the export of bacteriocins, such as SKF and subtilosin, which are antibacterial peptides targeting other bacteria. Some family members confer immunity to peptide antibiotics by exporting them, as seen with McbF, which is part of a complex responsible for the immunity to microcin B17. Others, like NosF, are implicated in the assembly of enzyme cofactors, specifically the copper chromophores of nitrous oxide reductase. Additional roles include involvement in exoprotein production, sporulation, and competence, as observed with EcsA. While some members have well-characterized functions, others remain uncharacterized, suggesting a potential for diverse and yet-to-be-discovered functions within the family.
NAD(P)-dependent oxidoreductase-like (NAD(P)-dependent_oxidoreduct)
Type: Family

This family of proteins includes enzymes that are involved in various metabolic processes, including the biosynthesis of sterols, antibiotics, and other bioactive molecules. Members of this family are characterised by their dependence on NAD(P) as a cofactor, performing functions such as oxidative decarboxylation, reduction, and dehydration reactions. These proteins are implicated in the modification of steroid molecules (NSDHL), the conversion of aurachins (AUAH) , and the biosynthesis of complex compounds like UCS1025A (UcsJ), which has antibacterial and antitumor properties . The family also includes enzymes that participate in the conversion of antibiotics, such 2'-dehydrokanamycin reductase which converts 2'-dehydrokanamycin A into kanamycin A, contributing to their bioactivation . The diverse enzymatic activities within this family reflect a broad functional repertoire, with each member playing a specific role in cellular metabolism and the biosynthesis of secondary metabolites.
Nodulation factor ABC transporter (Nod_factor_ABC_transporter)
Type: Family

This family of proteins is involved in the transport of specific bacterial signal molecules known as nodulation factors, which are essential for establishing symbiosis with host plants and triggering nodulation. These factors are lipooligosaccharides, specifically modified beta-1,4-linked N-acetylglucosamine oligosaccharides. Members of this family function as part of an ABC transporter complex, facilitating the export of these nodulation factors across the bacterial membrane.
Methylmalonyl-CoA/ethylmalonyl-CoA epimerase (MMCE/EMCE_epimerase)
Type: Family

This family of proteins includes enzymes that are primarily involved in the metabolism of propionyl-CoA and related compounds. Members of this family function as epimerases, catalyzing the reversible epimerization of methylmalonyl-CoA to its isomer. This reaction is a critical step in the degradation pathway of certain amino acids, odd-chain fatty acids, and cholesterol side chains, which converge into the propionyl-CoA metabolism. Some members exhibit promiscuity, also catalyzing the epimerization of ethylmalonyl-CoA, thereby participating in the ethylmalonyl-CoA pathway for acetyl-CoA assimilation in specific organisms. The family also includes proteins with a broader substrate range, such as those involved in the biosynthesis of secondary metabolites like cetoniacytone A.
Asparagine Synthetase/Amidase (ASN_synthetase/amidase)
Type: Family

This family of proteins includes enzymes that are primarily involved in the synthesis of asparagine from aspartate. Members of this family utilize glutamine as a nitrogen source in a two-step reaction, where glutamine is first hydrolyzed to glutamate and ammonia, and then the ammonia is transferred to aspartate to form asparagine. Some members are also implicated in the biosynthesis of secondary metabolites, such as the yellow pigment chrysogine, by catalyzing amidation reactions that contribute to the production of various compounds. The amidation process involves the transfer of an amino group from glutamine to a substrate molecule, which is a key step in the biosynthesis pathways of several bioactive molecules.
Major Facilitator Superfamily Transporter (MFS_Transporter)
Type: Family

This family of proteins includes members of the major facilitator superfamily (MFS), which are integral membrane transport proteins. They are likely involved in the transport of various substrates across cellular membranes. Some members are probable transporters with specificity for sugars such as glucose and mannose, while others may transport molecules related to rhizopine biosynthesis or other uncharacterized substrates. The functions of some members within this family remain to be fully characterized.
Bacterial Polyamine Transport Permease (Bact_Polyamine_Transport)
Type: Family

The PotC/PotI protein family is involved in the bacterial transport of polyamines, specifically putrescine and spermidine. Members of this family are integral components of the ABC transporter complex, which is essential for the uptake of these polyamines across the bacterial membrane. The PotC proteins function as part of the periplasmic transport system, while PotI proteins are responsible for the translocation of putrescine as part of the PotFGHI complex. The activity of these transporters is crucial for maintaining optimal concentrations of polyamines necessary for cell growth, especially in the presence of glucose. Additionally, the transport activity is regulated by the intracellular levels of polyamines, indicating a feedback inhibition mechanism to prevent excessive accumulation.
Cytochrome c-type biogenesis DsbD-related (Cytochrome_c-biogenesis_DsbD)
Type: Family

This family of proteins is involved in the biogenesis of cytochrome c, a component crucial for electron transport and energy production in cells. Members of this family are thought to facilitate the transfer of reducing equivalents, which is essential for the formation of proper disulfide bonds in cytochrome c and other proteins. They may function by shuttling these reducing equivalents across cellular membranes, such as the cytoplasmic membrane in bacteria or the thylakoid membrane in chloroplasts. In some cases, these proteins are also implicated in the assembly of the cytochrome b6f complex, a component of the photosynthetic electron transport chain in plants. Additionally, certain members may play a role in bacterial sporulation processes.
Proline-rich immunoreactive protein (Pra-immunoreactive)
Type: Family

This family of proteins includes members that are homologous to the mycobacterial Pra family, which are characterized by proline-rich regions. These regions are known to be immunoreactive, suggesting a role in immune response or interaction with the host immune system. The exact functions of the uncharacterized proteins within this family remain to be elucidated, but the presence of a domain that is highly immunoreactive in the N-terminus of some members indicates a potential role in pathogen-host interactions, possibly as antigens recognized by the host's immune system.
Gamma-glutamyltransferase, bacteria (GGT_bact)
Type: Family

This family of proteins includes enzymes that play a role in the metabolism of glutathione and related gamma-glutamyl compounds. Members of this family are involved in the cleavage of the gamma-glutamyl bond of glutathione, which leads to the release of free glutamate and the dipeptide cysteinyl-glycine. This process is important for the recycling of glutathione and for the regulation of its levels within the cell. Some family members also exhibit transpeptidase activity, which contributes to the biosynthesis of the peptidoglycan layer in bacteria by incorporating amino acids into the peptidoglycan scaffold. Additionally, certain enzymes within this family have been shown to possess acylase activity, which is involved in antibiotic biosynthesis. The activity of these enzymes is regulated by various compounds, including glucose and specific amino acids, indicating a complex role in cellular metabolism.
NADH:flavin oxidoreductase/NADH oxidase (NADH:flavin_oxidoreductase)
Type: Family

This family of proteins includes various NADH:flavin oxidoreductases and NADH oxidases. Members of this family are involved in a range of redox reactions, often utilizing NADH or NADPH as electron donors to reduce flavin or other substrates. They play roles in metabolic processes such as the beta-oxidation of unsaturated fatty acids, bile acid degradation , heme degradation and the reduction of metal ions. These enzymes typically contain binding domains for FMN, FAD, and NAD(P)H, and may have additional domains that contribute to their specific functions. They are characterised by their ability to catalyse oxidation-reduction reactions, which are essential for various cellular processes, including energy production and detoxification.
Peptidoglycan Endopeptidase C40 (PG_Endopeptidase_C40)
Type: Family

This family of proteins includes endopeptidases that play a role in bacterial cell wall metabolism. Members of this family are involved in the cleavage of peptidoglycan, specifically breaking the bond between D-glutamate and meso-diaminopimelate. This enzymatic activity is crucial for the proper separation of daughter cells following cell division, maintaining cell wall integrity, and is also implicated in host cell invasion. Some family members have been shown to bind high-molecular weight peptidoglycan without degrading it. Regulatory mechanisms for these proteins include modulation by other proteins, which can either enhance or inhibit their peptidoglycan degradation activity.
Glycosyl Hydrolase Family 43 (Glycosyl_Hydrlase_43)
Type: Family

The glycosyl hydrolase 43 family encompasses enzymes with diverse functions primarily involved in the degradation of complex carbohydrates. Members of this family include alpha-L-arabinofuranosidases and beta-xylosidases, which act on non-reducing ends of their respective substrates. Alpha-L-arabinofuranosidases cleave terminal alpha-L-arabinofuranoside residues in xyloglucan branches, facilitating the conversion of 'S' units to 'X' units and thus participating in xyloglucan degradation. Beta-xylosidases contribute to xylan degradation by breaking down beta-xylooligosaccharides into D-xylose units. Some family members also exhibit activity towards ulvan, a polysaccharide found in green seaweed, aiding in the degradation of its xylose-containing disaccharide building blocks. The family's enzymes are subject to inhibition by various metal ions and compounds, indicating a regulatory aspect to their activity in vivo.
Iron-sulfur flavoprotein SsuE-like (ISF_SsuE-like)
Type: Family

This family of proteins includes redox-active components likely involved in electron transport processes. Members are characterized by the presence of iron-sulfur clusters and flavin mononucleotide (FMN) as cofactors, which are indicative of their roles in various electron transfer reactions. These proteins are implicated in essential metabolic pathways, such as the fermentation of acetate to methane in certain archaea and potentially in the biosynthesis of complex molecules like antibiotics in bacteria. The family is unified by a shared structural motif that is typical of the SsuE-like proteins, suggesting a conserved mechanism of action across diverse biological contexts.
Transcription regulator TrmB-like (TrmB-like)
Type: Family

This family of proteins includes prokaryotic transcriptional regulators that interact with DNA to modulate gene expression in response to sugar availability, such as HTH-type sugar sensing transcriptional regulator TrmB from the hyperthermophilic archaea Pyrococcus furiosus, which contains an N-terminal DNA-binding domain with a winged-helix-turn-helix (wHTH) (

) and a C-terminal sugar-binding domain . Members of this entry bind to specific DNA sequences in gene promoters or operons, thus influencing the recruitment of RNA polymerase and the transcription of target genes. Regulatory activity is modulated by the binding of different sugars, which can induce or repress transcription of genes involved in carbohydrate transport and metabolism. Some family members form higher-order structures upon sugar binding that affect their DNA-binding affinity. This family also includes uncharacterised proteins like YrhO from Bacillus subtilis and MJ1082 from Methanocaldococcus jannaschii.
Class-II Pyridoxal-Phosphate-Dependent Aminotransferase (Class-II_PLP-Dep_Aminotrans)
Type: Family

This family of proteins includes enzymes that are primarily involved in the metabolism of sulfur-containing amino acids. Members of this family catalyze the transformation of cystathionine to homocysteine, a key step in the methionine biosynthesis pathway. Some proteins within this family also exhibit beta-cystathionase activity, breaking down cystathionine into pyruvate, ammonia, and thiocysteine. Additionally, certain members can act on cysteine-S-conjugates, cleaving the cysteine-S bond to release various compounds, including those contributing to human body odor. These enzymes are dependent on pyridoxal phosphate as a cofactor for their activity. Regulatory mechanisms for these proteins may include enhancement of activity by specific binding proteins, as indicated for at least one family member.
NADH-dependent flavin oxidoreductase (NADH_flavin_oxidoreductase)
Type: Family

The NADH-dependent flavin oxidoreductase family is involved in various biosynthetic and metabolic pathways. Members of this family participate in the biosynthesis of ilicicolin H, an antifungal compound, by contributing to the formation of the tetramic acid precursor and its subsequent conversion to acyclic 2-pyridone and 8-epi-ilicicolin H, with some acting as epimerases to produce the final ilicicolin H product. Another member is implicated in the aflatoxin biosynthesis pathway, specifically in the conversion of OMST to aflatoxin G1. Additionally, family members are involved in the degradation of organic compounds, such as the demethylation of N,N-dimethylglycine and sarcosine in glycine betaine degradation, and the cleavage of 4,4'-dithiodibutyric acid in disulfide degradation. The exact functions of some proteins within this family remain to be determined, highlighting the diversity of roles that these enzymes can play in various biological processes.
Intermembrane Transport Protein PqiA/PqiB (PqiA-PqiB_transport)
Type: Family

The PqiA/PqiB family includes intermembrane transport proteins that play a crucial role in maintaining membrane integrity. Members of the family are involved in a transport pathway that likely spans the intermembrane space, facilitating the movement of substrates across the periplasm. The proteins are probable components of a larger transport system, contributing to the stability and function of the cellular membrane structure.
Glycosyl_Hydrolase_28_Enzymes (GH28_Enzymes)
Type: Family

This family of proteins includes enzymes that are part of the glycosyl hydrolase 28 family. They are involved in the degradation of pectin, a plant cell wall polysaccharide, by catalyzing the hydrolysis of polygalacturonic acid. Members of this family contribute to various biological processes, including plant tissue maceration and soft-rotting, which is a mechanism in certain plant diseases. Some proteins in this family are implicated in the production of wilt disease in tomato plants by degrading the plant cell wall, facilitating bacterial invasion and colonization. Others are involved in bacterial utilization of polygalacturonate and may influence bacterial surface properties in the presence of plant cells or extracts.
Alpha-2-macroglobulin-like (YfhM-like)
Type: Family

This family of proteins includes Alpha-2-macroglobulin from Escherichia coli (YfhM) and similar proteins mainly found in bacteria. These proteins serve a protective role for the cell. They act as protease inhibitors, safeguarding the bacterial cell from host-derived peptidases . These proteins employ a 'trapping' mechanism, where cleavage of a specific bait-region domain by host peptidases triggers a conformational change. This change results in the entrapment of the peptidase and activation of a thioester bond, which covalently binds to the peptidase. Although trapped, the peptidases remain active but are inhibited from attacking large substrates. This defense mechanism may protect the periplasm and associated lipoproteins from external endopeptidases . The structural rearrangement upon cleavage is significant, altering over half of the protein's domain structure from its native to an induced form.

This entry also includes Circularly permutated Ras protein 2 from Dictyostelium discoideum (Cpras2), which shows regions of homology with the alpha-2 macroglobulins .
Type II TA system RelE-like toxin (TA_system_RelE-like_toxin)
Type: Family

This family of proteins includes toxic components of type II toxin-antitoxin (TA) systems. These toxins can inhibit cell growth and colony formation when expressed in bacteria such as E. coli. Their toxic effects are specifically neutralized by coexpression with their cognate antitoxins. In some cases, low levels of the toxin without its antitoxin can lead to decreased growth rates, cell death, or loss of colony formation abilities, and can result in greatly elongated cells. Mutations in these toxins can alter their effects on cell division and elongation.
Carbohydrate Metabolism Regulated Kinase/Isomerase (Carb_Metab_Reg_Kinase/Isom)
Type: Family

This family of proteins includes enzymes that are involved in carbohydrate metabolism. Members of this family are known to participate in the degradation of glucomannan, a polysaccharide composed of glucose and mannose. Some proteins in this family function as fructokinases, which are enzymes that phosphorylate fructose to fructose-6-phosphate, an important intermediate in the metabolism of sugars. Other members are mannose-6-phosphate isomerases, which catalyze the isomerization of mannose-6-phosphate to fructose-6-phosphate. The activity of these enzymes is regulated by metal ions, with zinc ions reported to inhibit several family members. Additionally, one protein is noted to be inactivated by EDTA, suggesting a requirement for divalent metal ions for its activity.
Dehydratase Activator and Reductase Protein (Dehydratase_Activator_Redct)
Type: Family

This family of proteins includes activators of various dehydratase enzymes and reductases involved in anaerobic fermentation pathways. Members of this family are responsible for activating dehydratase complexes through ATP-dependent electron transfer, which is crucial for maintaining an appropriate redox state of the dehydratases. These activators exhibit ATPase activity, which is essential for their function, and are highly sensitive to oxygen, indicating a role in anaerobic metabolic processes. Additionally, some members catalyze the reduction of benzoyl-CoA and its analogs, playing a role in the degradation of aromatic compounds. The proteins in this family share a common function in electron transfer and activation of dehydratases, despite being involved in different metabolic pathways.