SII-SWORD/CoKE huggingface dataset:
Bifunctional protease inhibitor (Bifunctional_prot_inhibitor)
Type: Family

This family of proteins includes inhibitors with bifunctional properties, each possessing two homologous halves with active inhibitory roles. One half is responsible for inhibiting trypsin, a serine protease involved in the digestion of proteins, while the other half targets elastase, another serine protease that breaks down elastin and other proteins. Additionally, some members of this family are characterized by having multiple Kazal family inhibitory domains, which are known to participate in protease inhibition. These domains are typically arranged in tandem and are evolutionarily related, suggesting a conserved mechanism of action across different species within this protein family.
4-Toluene sulfonate uptake permease/Inactive protease-like domain-containing protein (TSUP/Inactive_protease-like)
Type: Family

This family of proteins is involved in membrane transport, specifically in the uptake of solutes such as 4-toluene sulfonate. Members of this family are characterized by a conserved domain that suggests a role in the transport of specific substrates across the cell membrane, potentially functioning as permeases. Additionally, some proteins within this family contain an N-terminal region resembling a protease domain, although it is likely inactive as a protease. Instead, this domain may have a regulatory role in activating other proteases, such as MamE, and may be involved in complex biological processes like magnetite nucleation and formation. The dual functionality of these proteins, combining potential transporter activity with a regulatory role in proteolysis, underscores their multifaceted importance in cellular physiology.
Cell Envelope Integrity and Synthesis Associated Protein (Cell_Envelope_Assoc)
Type: Family

This family of proteins is involved in various cellular processes related to the integrity and function of the cell envelope. Some members are implicated in the barrier function of the cell envelope, which is crucial for maintaining the selective permeability required for cellular homeostasis and protection against environmental stress. Other members are associated with the metabolism of essential lipid carriers, playing a critical role in cell wall synthesis. Additionally, there are proteins within this family that may act as transcriptional activators and are involved in the inhibition of extrachromosomal maintenance of certain plasmids. The family also includes proteins that bind S-adenosyl-L-methionine, suggesting a potential role in methylation processes.
Beta-phosphoglucomutase-like (Beta-PGM-like)
Type: Family

This family of proteins includes enzymes that are primarily involved in the metabolism of various phosphorylated carbohydrates. The founding member of this family is Beta-phosphoglucomutase that catalyses the interconversion of D-glucose 1-phosphate and D-glucose 6-phosphate, forming beta-D-glucose 1,6-(bis)phosphate as an intermediate . Members of this family exhibit phosphatase activity, catalysing the dephosphorylation of sugar phosphates to their corresponding sugars. They are implicated in key metabolic pathways such as glycolysis and the pentose phosphate pathway, contributing to the regulation of carbohydrate intermediates and the synthesis of sugar nucleotides like UDP-glucose. Some family members have broader substrate specificity, acting on a range of sugar phosphate substrates, while others display more specialized activities towards specific substrates like 6-phosphogluconate, mannitol 1-phosphate, or sorbitol 6-phosphate . The enzymes in this family are structurally related, belonging to the HAD-like hydrolase superfamily, and are characterised by their ability to hydrolyse phosphomonoesters.
Serine protease/Carboxylesterase S33 (Serine_prot/Carboxylest_S33)
Type: Family

This family of proteins includes serine proteases and carboxylesterases that exhibit a range of activities, including cleaving tripeptides from the N-termini of proteins, modulating host immune responses, and promoting pathogenesis in certain bacterial infections. Some members have been identified as key virulence factors in mycobacterial species, affecting macrophage activation and immune response regulation. Others are involved in the biosynthesis of complex organic compounds, such as norsesquiterpenes, by participating in multi-step enzymatic pathways. The family is characterized by a conserved active site suggesting endopeptidase activity, and the protease activity is typically inhibited by serine protease inhibitors.
Acetyl-CoA Carboxylase Biotin Carboxylase Component (ACC_Biotin_Carboxylase)
Type: Family

This family of proteins includes enzymes that are integral components of the acetyl coenzyme A carboxylase complex. Members of this family are responsible for catalyzing the carboxylation of a carrier protein biotin, which is a crucial initial step in the biosynthesis of fatty acids. Following this, they facilitate the transfer of the carboxyl group to acetyl-CoA to produce malonyl-CoA, an essential building block for the elongation of fatty acid chains. The activity of these enzymes is fundamental to lipid metabolism and is conserved across various species, including plants, bacteria, and other organisms.
Zinc-Containing ADH Family: Quinone Oxidoreductase/CCCR (Zinc-ADH_QOR/CCCR)
Type: Family

The zinc-containing alcohol dehydrogenase family, specifically the quinone oxidoreductase and crotonyl-CoA carboxylase/reductase subfamilies, includes enzymes that play roles in various metabolic processes. Quinone oxidoreductase members do not exhibit alcohol dehydrogenase activity but bind NADP and transfer electrons to orthoquinones, aiding in xenobiotic detoxification. They also interact with AU-rich elements in the 3'-UTR of mRNAs to enhance stability, with NADPH binding modulating this interaction. Crotonyl-CoA carboxylase/reductase members catalyze the reductive carboxylation of crotonyl-CoA to ethylmalonyl-CoA, a key reaction in acetyl-CoA assimilation pathways. They also convert crotonyl-CoA to butyryl-CoA, contributing to straight-chain fatty acid biosynthesis. These enzymes exhibit substrate specificity and are regulated by various inhibitors, including NADPH and thiol group inhibitors.
Ergot Alkaloid Biosynthesis Oxidoreductase (Ergot_Alk_Oxidoreductase)
Type: Family

The fgaFS/easG family includes enzymes involved in the biosynthesis of ergot alkaloids, a group of secondary metabolites with diverse biological activities. Members of this family catalyze key reduction steps in the ergot alkaloid pathway, converting intermediates such as chanoclavine-I aldehyde to agroclavine and 6,8-dimethyl-6,7-didehydroergoline to festuclavine. These reactions are crucial for the formation of various ergot compounds, including ergopeptines like ergotamine and ergovaline. The family also encompasses enzymes involved in the biosynthesis of isofumigaclavines and the reduction of azo compounds in xenobiotics. The enzymes typically exhibit oxidoreductase activity, utilizing NAD(P)H as an electron donor to facilitate the reduction of their substrates.
Peptide Transporter Carbon Starvation (CstA)
Type: Family

The peptide transporter carbon starvation (CstA) family is involved in the uptake and utilization of peptides, particularly under conditions of carbon starvation. Members of this family transport dipeptides and tripeptides, which can be used as carbon sources for growth and survival. The transport process is typically driven by the proton motive force. Some members are known to be involved in additional biological processes such as host-pathogen interactions, bacterial motility, agglutination, and stimulation of dendritic cells. The family is part of a nutrient-sensing regulatory network in some bacteria, which includes two-component regulatory systems that control the expression and activity of these transporters.
Polyketide Oxidoreductase-like (Polyketide_Oxido-like)
Type: Family

This family of proteins includes oxidoreductases that play a crucial role in the biosynthesis of various secondary metabolites, including mycotoxins such as aflatoxins and sterigmatocystin, as well as other polyketide-derived compounds. Members of this family are involved in specific oxidation steps within the biosynthetic pathways. These enzymes typically catalyze the conversion of intermediate compounds to more complex structures, contributing to the formation of key functional groups and rings essential for the biological activity of the final products. The family also includes proteins that are involved in the reduction of various flavins and other substrates, indicating a broad specificity and a role in diverse metabolic processes.
Metallo-dependent Hydrolases (Metallo-dep_hydrolases)
Type: Family

This family of proteins includes enzymes that catalyze the hydrolysis of specific substrates to produce ammonia. One member is known to hydrolyze N-formimino-L-glutamate to N-formyl-L-glutamate and ammonia. The majority of the family members are involved in the hydrolytic deamination of guanine to xanthine and ammonia. Some proteins within this family may also have additional enzymatic activities, such as the deamination of 7,8-dihydropterin, which contributes to the synthesis of certain pigments. Members of this family are inhibited by various compounds, which can include metal chelators, specific substrate analogs, and other inhibitors that affect enzymatic activity towards particular substrates. All members belong to the metallo-dependent hydrolases superfamily, with several being part of the ATZ/TRZ family, indicating a dependency on metal ions for their catalytic activity.
Ribosome Quality Control Complex Subunit NEMF (RQC_Subunit_NEMF)
Type: Family

The NEMF family is involved in the ribosome quality control complex (RQC), which addresses stalled ribosome issues by mediating the extraction and degradation of incomplete nascent polypeptide chains. NEMF proteins bind to stalled ribosomal subunits, recognizing nascent chain-conjugated tRNA moieties. They facilitate CAT tailing by recruiting alanine-charged tRNA to the ribosomal A-site, leading to non-templated C-terminal alanine extensions. This process is crucial for exposing lysine residues for ubiquitination and subsequent proteasomal degradation, preventing the accumulation of potentially toxic nascent chains. Additionally, NEMF proteins may play roles in nuclear export, cell cycle regulation, DNA damage-induced apoptosis, mitochondrial stress responses, and binding to extracellular matrix proteins, contributing to bacterial virulence.
NmrA-type/Isoflavone reductase-like domain-containing protein (NmrA/Isoflavone_reductase-like)
Type: Family

This family of proteins includes oxidoreductases involved in various biosynthetic pathways. Members of this family participate in the synthesis of diverse bioactive compounds, including cytotoxic compounds, antifungal agents, meroterpenoids, and fungal alkaloids. They function in the reduction of intermediates, catalyzing reactions that contribute to the formation of complex molecules with potential pharmacological applications. These proteins are characterized by their similarity to the NmrA-type oxidoreductase family and often belong to the isoflavone reductase subfamily, indicating a role in the reduction of isoflavone-like molecules.
Glucose-6-phosphate isomerase/Oxalate decarboxylase (GPI/OXD)
Type: Family

This family of proteins includes enzymes that are involved in the isomerization of glucose-6-phosphate and the decarboxylation of oxalate. Some members catalyze the conversion of glucose-6-phosphate into fructose-6-phosphate, a key step in glycolysis and gluconeogenesis. Other members convert oxalate into formate and carbon dioxide, which may occur in an oxygen-dependent manner. These enzymes can also catalyze side reactions such as oxalate oxidation and dye oxidations. The activity of some isomerases in this family is regulated by various metabolites and metal ions, indicating a role in metabolic regulation.
Energy-coupling factor transporter component (ECF_transporter_component)
Type: Family

This family of proteins includes transmembrane components of energy-coupling factor (ECF) transporter complexes, which are a type of ATP-binding cassette (ABC) transporter. Unlike classic ABC transporters, ECF transporters do not require external ATP hydrolysis for function, as they harness energy from the transmembrane electrochemical gradient. These proteins are involved in the import of various substrates, such as nickel, cobalt, 5-formyltetrahydrofolate, and thiamine. Some family members are specifically implicated in nickel transport as part of the ECF transporter complex, contributing to metal ion homeostasis.
Teichoic Acid Biosynthesis Enzymes (Teichoic_Acid_Biosynth)
Type: Family

This family of proteins is involved in the biosynthesis of teichoic acids, which are components of the cell wall in certain bacteria. Members of this family function as enzymes that catalyze the transfer of glycerol phosphate or ribitol phosphate units from cytidine diphosphate-activated donors to a growing polymer chain attached to a disaccharide linkage unit. These enzymes are responsible for the polymerization of the main chain of major teichoic acids, synthesizing polymers of glycerol phosphate or ribitol phosphate of varying lengths. Some members act as primases, initiating the polymerization process by adding the first phosphate unit, while others extend the polymer by adding multiple units.
ABC transporter permease HisMQ subfamily (ABC_transp_permease_HisMQ)
Type: Family

This family of proteins is involved in the transport of various amino acids and related compounds across cellular membranes. They are part of the ABC transporter complex, which typically includes multiple subunits that work together to translocate substrates. These proteins are likely responsible for the movement of substances such as arginine, histidine, lysine, ornithine, octopine, and nopaline. They function by coupling the energy derived from ATP hydrolysis to the active transport of these molecules, facilitating their uptake into the cell. The proteins in this family are characterized by their role in signaling and substrate translocation, which is essential for nutrient acquisition and various metabolic processes.
UPF0045 domain-containing protein (UPF0045_domain)
Type: Family

This family of proteins is characterized by the UPF0045 domain. The specific functions of proteins within this family are diverse and not fully characterized. However, they are generally believed to be involved in various cellular processes, including but not limited to, metal ion binding and potential roles in enzymatic activity or regulation. The UPF0045 domain is found across a wide range of organisms, indicating a conserved function that is essential for basic cellular functions. Further research is necessary to elucidate the precise roles of these proteins in different species.
Transcriptional Regulatory Elements (Transcr_Regulatory_Elem)
Type: Family

This family of proteins includes transcriptional regulatory elements that are involved in various biological processes. Members of this family are known to bind specific DNA sequences and activate the transcription of genes related to nitrogen assimilation, such as nitrate and nitrite reductases. Some proteins within this family are also involved in the regulation of morphogenesis, such as conidiophore development, and in the modulation of biofilm formation and host infection. Additionally, certain family members contain domains that suggest a role in gene expression activation, including a glutamine-rich domain and a transactivation domain. The diversity of functions reflects the versatile roles of these proteins in cellular regulation and organismal development.
Cul2-RING E3 ligase substrate-recognition (Cul2-RING_E3_ligase_SR)
Type: Family

The protein family includes members that function as substrate-recognition components of a Cul2-RING E3 ubiquitin-protein ligase complex within the DesCEND pathway. They are responsible for recognizing and binding to C-degrons located at the extreme C terminus of target proteins. This recognition leads to the ubiquitination and subsequent degradation of these proteins. The C-degron is typically a motif of less than ten residues and may be present in proteins whether they are full-length, truncated, or proteolytically cleaved forms. The family is characterized by the presence of ankyrin repeats, which are known to mediate protein-protein interactions.
UNC-93-like transmembrane regulator (UNC-93-like_regulator)
Type: Family

This family of proteins includes members that are similar to the UNC-93 protein, which is known to be involved in various biological processes. The UNC-93 family is characterized by its role in the regulation of ion channel activity and intracellular signaling pathways. Members of this family are typically transmembrane proteins that may function in the transport of molecules across membranes or in the modulation of signaling cascades. The family includes proteins that are structurally related and share functional motifs, suggesting a conserved mechanism of action across different species. While the specific functions of individual family members may vary, they are generally associated with cellular homeostasis and communication.
Actin-binding LIM (Actin-binding_LIM)
Type: Family

The Actin-binding LIM protein family is involved in various cellular processes related to actin dynamics and cytoskeleton organization. Members of this family function as scaffold proteins, potentially interacting with other proteins to modulate actin filament assembly and organization. They play roles in cell shape maintenance, motility, and migration by regulating actin bundling and the formation of cell protrusions such as filopodia and lamellipodia. Some family members are implicated in intracellular signaling pathways, including the regulation of protein kinase A (PKA) activity and RhoA activation. They may also participate in transcriptional regulation through ABRA-dependent SRF activity. In specialized cells, they contribute to functions like erythrocyte shape integrity, platelet aggregation, and retinal development. The family includes tumor suppressors that inhibit malignant transformation.
Type II TA system ribonuclease PINc/VapC (TypeII_TA_RNase_PINc/VapC)
Type: Family

The PINc/VapC protein family consists of toxic components of type II toxin-antitoxin (TA) systems, characterized by their ribonuclease (RNase) activity. Members of this family are involved in bacterial stress response and can inhibit cell growth or lead to dormancy when expressed. The toxicity of these proteins is counteracted by their cognate antitoxins, VapB proteins, with which they form stable complexes. Some family members have additional activities, such as slow ssDNA exonuclease activity, and their functions can be inhibited by chelating agents like EDTA. The PINc/VapC family plays a crucial role in the regulation of bacterial cell fate under various stress conditions, and their study is important for understanding bacterial persistence and pathogenicity.
ORF904-like, C-terminal domain (ORF904-like_C)
Type: Domain

This family represents a novel class of multifunctional replicative enzymes that combine ATPase, primase and DNA polymerase activities within a single polypeptide chain. ORF904 from Sulfolobus islandicus plasmid pRN1 demonstrates all three enzymatic activities and is essential for autonomous plasmid replication. Proteins in this family are characterised by the presence of three distinct functional domains: an N-terminal region containing primase and DNA polymerase activities with sequence similarity to family X DNA polymerases and archaeal primases, and a C-terminal region harbouring ATPase activity with a conserved Walker A motif (A/G X4GK S/T) essential for nucleotide binding and ATP hydrolysis. The DNA polymerase domain shows preference for double-stranded DNA templates and demonstrates processive synthesis, while the primase domain synthesises short RNA primers on single-stranded DNA templates. The ATPase domain exhibits DNA-dependent ATP hydrolysis activity. This unique domain architecture allows a single protein to perform multiple essential replication functions typically distributed among separate enzymes in larger replicons, representing an evolutionary adaptation to the constraints of small genetic elements .
Type II secretion system protein J (T2SS_protein_J)
Type: Family

This family of proteins is involved in the type II secretion system, which is an energy-dependent process that transports extracellular factors such as proteases and toxins from the periplasm. Members of this family are part of the pseudopilus tip complex, playing a crucial role in the recognition and binding of secretion substrates. Some members may also contribute to increased bacterial adhesive capabilities.
Receptor-type Tyrosine-protein Phosphatases (R-tyr_protein_phosphatases)
Type: Family

The Receptor-type tyrosine-protein phosphatase family is involved in various cellular processes, including cell-cell interactions, signal transduction, cellular adhesion, and cell proliferation and migration. Members of this family play roles in the modulation of key signaling pathways by dephosphorylating substrates such as p120 catenin, CTNND1, and CTNNB1, which influence cell adhesion, glucose transporter function, and Wnt signaling. Some members are implicated in CNS function, adipogenic differentiation, epithelial integrity, and may have roles in tumor suppression by negatively regulating growth factor signaling pathways. The family contributes to the maintenance of cellular integrity and is involved in developmental processes such as somitogenesis.
Formiminotransferase-cyclodeaminase (FTCD)
Type: Family

This family of proteins includes enzymes that are involved in folate metabolism, specifically in the transfer of one-carbon units. Members of this family exhibit formiminotransferase activity, catalyzing the transfer of formyl and formimino groups to tetrahydrofolate (THF), producing different forms of folate such as 5-formyltetrahydrofolate and 5-formiminotetrahydrofolate. Some proteins within this family also display cyclodeaminase activity, contributing to the conversion of these folate derivatives further within the folate cycle. Additionally, certain members are implicated in cytoskeletal interactions, particularly in the bundling of vimentin filaments. This dual functionality suggests a role in both metabolic processes and cellular structure maintenance.
RMD1/Sad1-interacting (RMD1/Sad1-interacting)
Type: Family

This family of proteins is involved in various cellular processes including sporulation, mitochondrial translation, and maintenance of mitochondrial structure. Members are believed to play roles in meiotic nuclear division during sporulation. In mitochondria, they are thought to coordinate the assembly or maintenance of the mitochondrial ribosome, which is essential for protein synthesis within the organelle. Some family members are also implicated in plant growth regulation by affecting cell division and expansion in root meristems, as well as mediating abscisic acid signal transduction during seed germination and seedling growth.
Diverse Signaling and Regulatory Domain-Containing Protein (Signaling_Regulatory_Domain)
Type: Family

This family of proteins includes members with diverse functions related to cellular signaling and regulation. Some act as inhibitors of tyrosine kinase activity, playing a role in B-cell development and modulating signaling pathways such as NF-kappa-B transcription. Others are involved in cell cycle regulation through chromatin remodeling. Additionally, members of this family may function in membrane trafficking and protein ubiquitination, serving as guanine nucleotide exchange factors (GEFs) for Arf and Rab GTPases, or acting as E3 ubiquitin-protein ligases, mediating ubiquitination and proteasomal degradation of target proteins. The presence of BTB domains suggests a role in protein-protein interactions, possibly in targeting to specific cellular compartments such as acrosomal vesicles.