SII-SWORD/CoKE huggingface dataset:
Homeobox domain-containing regulator (Homeobox_regulator)
Type: Family

This family of proteins includes transcriptional regulators with homeobox domains that are involved in early embryonic development, axis formation, and myogenesis. Members of this family can act as transcriptional activators or repressors, binding to specific DNA elements to regulate gene expression. Some proteins within this family are implicated in the formation of the Spemann organizer and the Nieuwkoop center, essential for dorsoventral axis formation in embryos. They also play roles in neural induction and the regulation of microRNA expression. Certain family members are associated with muscle regeneration, potentially influencing the expression of myogenic factors and miRNAs. The homeobox domains are key for DNA binding and nuclear localization, while additional regions may contribute to transcriptional activation or repression.
Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 4 (OST4)
Type: Family

The OST4 family consists of subunits within the oligosaccharyl transferase (OST) complex, which is pivotal for protein N-glycosylation. These subunits facilitate the transfer of a specific glycan, Glc(3)Man(9)GlcNAc(2), from dolichol-pyrophosphate to an asparagine residue in nascent polypeptide chains. This transfer occurs within an Asn-X-Ser/Thr motif and is a cotranslational process. The OST complex operates in conjunction with the Sec61 complex at the translocon in the endoplasmic reticulum, enabling protein translocation. All subunits are essential for the complex's full enzymatic activity. Members of the OST4 family are also involved in maintaining the stability of STT3A-containing OST complexes.
Plant Proline-Rich Cell Wall Protein (Proline-rich_CW_protein)
Type: Family

This family of proteins includes developmentally regulated cell wall proteins, primarily from plants, which are rich in proline residues. Members of this family are involved in various stages of plant development and interactions with symbiotic organisms. Some proteins are implicated in the modification of cell-wall structure, which may be crucial during processes such as seed germination and root nodule development. Others are associated with the plant's response to symbiotic bacteria, playing roles in the infection process and the establishment of nitrogen-fixing nodules. The diversity of functions reflects the importance of these proteins in plant growth and adaptation to environmental interactions.
ABC transporter ABCF subfamily ATPase (ABCF_ATPase)
Type: Family

This family of proteins is part of the ATP-binding cassette (ABC) transporter superfamily, specifically within the ABCF subfamily. Members are involved in various cellular processes, including ribosome assembly or function, and may play a role in the resolution of branched DNA intermediates arising from template switching during DNA replication. Some proteins within this family have been implicated in antibiotic resistance by recognizing and binding to ribosomes stalled by certain antibiotics, leading to the dislodgement of these drugs from their binding sites. Additionally, certain members are associated with DNA binding and possess ATPase activity, which is not altered by the presence of DNA. The family includes proteins that may contribute to bacterial virulence through involvement in cell adhesion to surfaces.
Methyl-accepting chemotaxis (MCP_chemotaxis)
Type: Family

The Methyl-accepting chemotaxis (MCP) protein family consists of chemotactic signal transducers that mediate bacterial taxis in response to environmental stimuli. Members of the MCP family detect the presence of attractants and repellents, initiating a signal transduction process that alters the swimming behavior of the cell. Attractants cause an increase in the level of methylation of these proteins, while repellents result in decreased methylation. The reversible methylation, which is regulated by the methyltransferase CheR and the methylesterase CheB, facilitates sensory adaptation, allowing the bacteria to respond to changes in the concentration of environmental cues. The MCP proteins interact with various periplasmic binding proteins to mediate taxis towards or away from specific compounds, such as sugars, amino acids, dipeptides, and gases. Some members are also involved in virulence and pathogenesis, and may contain additional domains for sensing specific stimuli, like oxygen or redox state.
DedA domain-containing protein (DedA_domain)
Type: Family

This family of proteins includes members that are involved in the transport of undecaprenyl phosphate (UndP) across the cytoplasmic membrane. These proteins function as flippases, facilitating the movement of UndP from the external side to the cytoplasmic side of the membrane. This process is crucial for the recycling of UndP during the synthesis of peptidoglycan, which is an essential component of the bacterial cell wall. The family is characterized by the presence of DedA domain-containing proteins, which are implicated in membrane-related processes. While some proteins within this family remain uncharacterized, the common feature among annotated members is their association with membrane transport and potential involvement in cell envelope biogenesis.
Diverse Substrate Oxidoreductases (Diverse_Substr_Oxidored)
Type: Family

The protein family encompasses a variety of enzymes that catalyze oxidation-reduction reactions across different biological processes. Members are involved in the metabolism of purines, phenolic compounds, aldehydes, and other substrates such as nicotine and caffeine. They function as key enzymes in pathways like purine salvage, anaerobic degradation of phenolic compounds, detoxification of aldehydes, and degradation of nicotine and caffeine. These enzymes are characterized by their binding to FAD and are found in various organisms, indicating a broad biological significance. The family includes dehydrogenases and oxidoreductases, which may function as dehydrogenases or oxidases, and are involved in both catabolic and detoxification processes. They exhibit diverse substrate specificities and are regulated by different factors, including the presence of other protein subunits and chemical inhibitors.
Bacterial iron-siderophore binding (Bact_iron-sidero_bind)
Type: Family

The bacterial solute-binding protein 8 family is involved in the uptake of iron through various siderophores, which are molecules that bind and transport iron into cells. Members of this family are typically part of ABC transporter complexes and function as periplasmic binding proteins. They bind iron complexes such as ferric citrate, ferric hydroxamate, and other iron-siderophore complexes, and then deliver these complexes to membrane-bound permeases for transport into the cytoplasm. The siderophores recognized by this family include bacillibactin, enterobactin, ferrichrome, aerobactin, petrobactin, and anguibactin, among others. The binding specificity and transport function are crucial for bacterial iron acquisition, especially in iron-limited environments, contributing to the survival and virulence of various bacterial species.
AAA ATPase RarA/MGS1/WRNIP1 (AAA_ATPase_RarA/MGS1/WRNIP1)
Type: Family

This family of proteins includes ATPases associated with various cellular activities, particularly those involved in DNA replication and repair processes. Members of this family are characterized by an AAA ATPase domain that provides energy for their functions through the hydrolysis of ATP. They play crucial roles in responding to stalled DNA replication forks, maintaining DNA topology, and ensuring chromosome integrity. Some members are involved in modulating DNA polymerase delta-mediated DNA synthesis, either by stimulating or decreasing it in the presence of ATP. Additionally, certain proteins within this family contribute to the innate immune defense against viruses by interacting with components of the antiviral signaling pathway, such as RIGI and MAVS, and promoting specific polyubiquitination events that facilitate signal transduction.
Bacterial Chemotaxis Sensor Histidine Kinase CheA (Bact_Chemotaxis_CheA)
Type: Family

The CheA protein family is central to bacterial chemotaxis, a process where bacteria navigate their environment by moving towards favorable chemical stimuli and away from harmful ones. Members of the CheA family function as sensor histidine kinases that autophosphorylate in response to signals from chemoreceptors. Once phosphorylated, CheA proteins can transfer the phosphate group to response regulators such as CheB and CheY, which modulate the activity of flagellar motors, altering the swimming behavior of the cell. Some family members also respond to phototactic signals and may interact with additional proteins like CheV. The domains within these proteins facilitate interaction with response regulators, regulate phosphorylation, and receive sensory input to control activity.
Zinc-regulated GTPase metalloprotein activator (Zinc-reg_GTPase_activator)
Type: Family

This family of proteins functions as zinc chaperones, facilitating the transfer of zinc ions to target metalloproteins, which results in their activation. The proteins possess a GTPase domain with a CXCC motif that binds zinc and, upon GTP hydrolysis, transfers the zinc to specific binding sites on metalloproteins. This process is essential for the proper function of metalloenzymes such as methionine aminopeptidase METAP1, which cleaves initiator methionine from nascent polypeptides. The activity of these GTPases is regulated by metal binding; zinc inhibits while other metals like Co(II) and Ni(II) decrease the GTPase activity. These proteins are part of the SIMIBI class G3E GTPase family within the ZNG1 subfamily.
Gfo/Idh/MocA family oxidoreductases (Gfo/Idh/MocA_oxidoreduct)
Type: Family

The Gfo/Idh/MocA family includes a diverse set of oxidoreductases involved in various metabolic processes. Members of this family are characterized by their ability to catalyze oxidation-reduction reactions pivotal to the metabolism of sugars and other compounds. Functions of characterized members include the catabolism of D-apiose, the reversible reduction of scyllo-inosose to scyllo-inositol, the biosynthesis of kanosamine and aspirochlorine, and the regulation of lactose/galactose metabolic genes. The family exhibits a broad substrate specificity, with some members preferring NADPH as a cofactor, while others utilize NAD. The family's involvement in antibiotic and antifungal compound biosynthesis highlights its potential importance in microbial defense mechanisms. The regulatory roles in sugar metabolism suggest additional layers of complexity in gene expression control within this family.
Iron-sulphur-dependent L-serine dehydratase (Fe-S_L-Ser)
Type: Family

The iron-sulfur dependent L-serine dehydratase family is characterised by enzymes that catalyse the deamination of L-serine to pyruvate and ammonia, a reaction that plays a crucial role in the metabolism of serine and in the overall carbon and nitrogen balance within the cell. Some members of the family are also known to deaminate threonine, like L-serine dehydratase 1/2 from Escherichia coli, especially under conditions of high substrate concentration. Proteins in this group are mainly found in bacteria.
Bifunctional oligoribonuclease/pAp-phosphatase and c-di-AMP PDE (Oligoribo/pAp-PDE_c-di-AMP_PDE)
Type: Family

The protein family includes bifunctional enzymes with oligoribonuclease and pAp-phosphatase activities, degrading RNA and DNA oligonucleotides up to 33 nucleotides in length, with a preference for shorter substrates. They convert 3'(2')-phosphoadenosine 5'-phosphate (PAP) to AMP, playing a role in RNA metabolism and regulation. Some family members also exhibit cyclic-di-AMP phosphodiesterase activity, impacting cellular processes like growth, DNA repair, and cell wall homeostasis. They may also respond to cellular heme or nitric oxide levels. The family includes uncharacterized proteins, suggesting potential undiscovered functions.
Viral Replication and Maturation Polyprotein (Viral_Replic_Matur_Polypro)
Type: Family

The protein family is involved in the replication and maturation of viral genomes. Members encode polyproteins that are processed to yield proteases and reverse transcriptases. The protease activity cleaves the polyprotein in cis, while the reverse transcriptase exhibits DNA polymerase activity, copying DNA or RNA templates, and ribonuclease H activity, cleaving RNA-DNA heteroduplexes. The reverse transcription process encapsulates pregenomic RNA, synthesizing a relaxed circular DNA genome that migrates to the nucleus post-infection, converting into covalently closed circular DNA. Some members also integrate viral DNA into the host genome and are involved in virion maturation and capsid assembly.
Polyhydroxyalkanoate Synthase (PHA/PHB_synthase)
Type: Family

The PHA/PHB synthase family is involved in the biosynthesis of polyhydroxyalkanoates (PHAs), which are biopolymers synthesized by various microorganisms as intracellular energy reserves under nutrient-limiting conditions. The primary function of the family members is to polymerize 3-hydroxybutyryl-CoA into poly(3-hydroxybutyrate) (PHB) or copolymers such as poly(beta-hydroxybutyrate-co-beta-hydroxyvalerate) (PHBV). These polymers consist of thousands of hydroxybutyrate molecules linked end to end. PHB and PHBV are water-insoluble and serve as energy storage materials. The catalytic activity of some subunits is enhanced by non-catalytic subunits, indicating a complex interaction within the family for efficient polymer production. The family includes several subfamilies, each with specific features and potentially different substrate specificities or product profiles.
Amino Acid ABC Transporter Permease (AA_ABC_Transporter_Permease)
Type: Family

The protein family is involved in the transport of various amino acids across the cell membrane. Members of the family function as part of different ABC transporter complexes, facilitating the translocation of substrates such as histidine, lysine, arginine, ornithine, and D-methionine. Some proteins within the family are also implicated in the transport of toxic analogs like alpha-methyl-methionine and may participate in microbial infection processes by transporting toxin components. The family includes subfamilies that are responsible for signaling between the solute-binding proteins and the ATPase components of the transport system, indicating a role in the regulation of transport activity.
Alpha-ketoglutarate-dependent sulfate ester dioxygenase-like (AtsK-like)
Type: Family

This entry represents Alpha-ketoglutarate-dependent sulfate ester dioxygenase	Pseudomonas putida (AtsK) and similar proteins
involved in diverse biological processes, including the degradation of sulfonates and sulfate esters, as well as the biosynthesis of natural products such as indole alkaloids and sesterterpenes. Members of this family catalyse oxidative reactions that typically result in the cleavage of C-S bonds in sulfonates or the hydroxylation of substrates, often yielding products like sulfite, succinate, or specific intermediates in complex biosynthetic pathways. Some proteins within this family are also implicated in the degradation of herbicides and resistance to antitubercular compounds. The enzymes are characterised by their requirement for alpha-ketoglutarate as a co-substrate and are regulated by various factors, including metal ions and ascorbate.
Stress and Tellurium Resistance Protein (Stress/Tellurium_Resist)
Type: Family

This family of proteins is associated with resistance to various stress factors, including tellurium, phage infection, and colicin. Members of this family appear to play a role in the tellurium resistance mechanism, although the exact functions are not fully characterized. Some proteins in this family are also implicated in resistance to chemical-damaging agents such as methyl methane sulfonate and mitomycin C, as well as to UV radiation. The involvement in multiple resistance pathways suggests a general role in stress response and cellular defense mechanisms.
Nudix hydrolase domain-containing protein (Nudix_hydrolase_domain)
Type: Family

This family of proteins includes enzymes with decapping and hydrolytic activities, primarily involved in the metabolism of nucleotide-like molecules. Members of this family are capable of removing the 5'-end m7GpppN cap from viral and host mRNAs, a process essential for mRNA decay. This decapping activity is crucial for regulating mRNA turnover and may influence host protein synthesis by promoting the degradation of host mRNAs and facilitating stage-specific viral protein synthesis. Some family members also exhibit hydrolytic activity towards diphosphoinositol polyphosphates and other nucleotide polyphosphates, such as diadenosine tetraphosphate (Ap4A), which they asymmetrically hydrolyze to yield AMP and ATP. These activities suggest a role in modulating cellular processes, including the secretory pathway, potentially impacting virion formation and other cellular functions.
Kynurenine--oxoglutarate transaminase (Kynurenine-oxoglutarate_AT)
Type: Family

The Kynurenine--oxoglutarate transaminase family includes enzymes that catalyze the irreversible transamination of L-kynurenine to form kynurenic acid, an intermediate in the tryptophan catabolic pathway and a broad-spectrum antagonist of ionotropic excitatory amino acid receptors. Members of the family also metabolize cysteine conjugates of halogenated alkenes and alkanes to form reactive metabolites and catalyze the beta-elimination of S-conjugates and Se-conjugates of L-(seleno)cysteine, resulting in the cleavage of the C-S or C-Se bond. Some members show activity with various amino acids and keto-acids as amino group acceptors. The family belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family, indicating a dependence on pyridoxal phosphate as a cofactor for their enzymatic activity.
Multi Antimicrobial Extrusion Protein MepA (MATE_MepA_subfamily)
Type: Family

The MepA subfamily of the multi antimicrobial extrusion (MATE) family is comprised of multidrug resistance efflux proteins. Members of the MepA subfamily are involved in the active transport of a variety of clinically relevant antimicrobial agents, including monovalent and divalent biocides, as well as fluoroquinolone antibiotics like norfloxacin and ciprofloxacin. These proteins play a crucial role in bacterial resistance by expelling toxic compounds out of the cell, thereby reducing their intracellular concentration and effectiveness. The MepA subfamily is also implicated in the regulation of virulence factors, as it is required for the transcription of agr and RNAIII, and influences the production of protein A and several toxins in Staphylococcus species.
Type VII Secretion & ABC Transporter Permease (T7SS_ABC-Transporter)
Type: Family

This family of proteins includes components of the type VII secretion system (Ess) and ABC transporter permeases. The Ess components, such as EsaA, are involved in forming a secretion platform across the cytoplasmic membrane, working in conjunction with other proteins like EssB, EssC, and EssE to facilitate the secretion process. The ABC transporter permeases, such as DrrB, are part of the ABC transporter complex and are likely responsible for the translocation of substrates, including antibiotics like doxorubicin, across the membrane, contributing to antibiotic resistance.
Nitrite and Sulfite Reductase 4Fe-4S Domain-Containing Protein (NIR_SIR_4Fe-4S)
Type: Family

This family of proteins includes enzymes that are involved in the reduction of nitrite to ammonium and sulfite to sulfide. These reactions are crucial steps in the nitrogen and sulfur assimilation pathways, respectively. The proteins utilize a 4Fe-4S domain to transfer electrons, typically from ferredoxin, to facilitate these reductions. Some members of the family are localized to the chloroplast and are involved in the assimilation of nitrite during photosynthesis. Others participate in the biosynthesis of sulfur-containing amino acids and cofactors. The family is characterized by the presence of a 4Fe-4S domain, which is indicative of their role in electron transfer processes.
Phosphatase regulators and Met sulfoxide reductases (Phosphatase_reg/MetRdx)
Type: Family

This family of proteins includes regulators of serine/threonine-protein phosphatases, particularly PP2A and PP4, and free methionine-R-sulfoxide reductases. Members involved in phosphatase regulation may act as allosteric regulators or inhibitors, affecting the catalytic activity and complex formation of these phosphatases. They are implicated in various cellular processes, including the DNA damage response and the regulation of the TOR signaling pathway. Other members of the family are involved in the reversible reduction of methionine sulfoxide to methionine, playing a role in cellular protection against oxidative stress.
Chorismate mutase-related enzymes (Chorismate_mutase-related)
Type: Family

This family of proteins is involved in the biosynthesis of aromatic amino acids and other aromatic compounds through the Claisen rearrangement of chorismate to prephenate. Members of this family may also participate in the biosynthesis of various secondary metabolites, such as siderophores and antibiotics, by catalyzing related rearrangement and elimination reactions. Some proteins within this family are secreted and may contribute to pathogenicity, while others are intracellular and are regulated by complex formation or feedback inhibition by aromatic amino acids.
Fosfomycin Resistance Enzymes (Fosfomycin_Res_Enzymes)
Type: Family

This family of proteins includes enzymes that confer resistance to the antibiotic fosfomycin. Members of this family are involved in the modification of fosfomycin, thereby inactivating its antibacterial properties. The primary mechanism involves the catalysis of the addition of a thiol or glutathione group to fosfomycin. Some members require potassium ions for optimal activity. Additionally, certain proteins within this family are capable of catalyzing the hydration of fosfomycin. These activities are crucial for bacterial survival in the presence of fosfomycin and are a part of the broader antibiotic resistance mechanisms found in various bacteria.
CLIP domain-containing serine protease (CLIP_Serine_Protease)
Type: Family

The CLIP domain-containing serine protease family is involved in innate immune responses across various organisms. Members of this family play key roles in pathogen recognition and activation of immune cascades, particularly in response to infections by parasites, bacteria, and fungi. They are characterized by a clip domain that forms a compact structure through conserved disulfide bonds. These proteases are involved in processes such as the melanization cascade, which results in the clearance of pathogens, and the activation of the Toll pathway, crucial for defining cell identities during embryonic development. They also contribute to the activation of prophenoloxidase, leading to melanin formation, and are implicated in the digestion process and sperm activation during mating.
Serine/Arginine-Rich Protein Kinases (SRPK)
Type: Family

The SRPK family comprises serine/threonine-protein kinases that specifically phosphorylate serine residues within arginine/serine-rich (RS) domains of splicing factors and other substrates. These kinases play a central role in the regulation of splicing, influencing the intranuclear distribution of splicing factors and the reorganization of nuclear speckles. Their activity is essential for various cellular processes, including mRNA maturation, chromatin reorganization, cell cycle progression, and muscle development. Some family members are implicated in neuronal apoptosis through the up-regulation of cyclin-D1 and the suppression of p53 phosphorylation. Additionally, they may participate in spliceosomal B complex formation and the suppression of transcription-associated R-loops. The SRPK family also has a role in viral replication regulation, such as reducing hepatitis B virus replication efficiency.