SII-SWORD/CoKE huggingface dataset:
Transcriptional Regulatory Proteins (Transcr_Regulatory_Proteins)
Type: Family

This family of proteins includes transcriptional regulators involved in various biological processes. Members of this family are responsible for regulating the expression of genes that govern cell state transitions, sexual development, and secondary metabolite biosynthesis. They play roles in maintaining the stability of phenotypic states, such as the white and opaque states in fungi, which are important for mating and virulence. Some members induce sexual development and are involved in calcium homeostasis. Others regulate the production of bioactive compounds with antimalarial, antiviral, antibacterial, antifungal, antitumor, and phytotoxic properties. The functions of some members within this family remain uncharacterized.
F-box domain-containing protein (F-box_domain)
Type: Family

This family of proteins includes members that are part of SCF (SKP1-cullin-F-box) E3 ubiquitin ligase complexes, which are involved in the ubiquitination and subsequent proteasomal degradation of target proteins. These proteins typically contain an F-box domain that is essential for interaction with SKP1 and other proteins within the complex. The family plays a role in various cellular processes by targeting specific proteins for degradation, which can regulate pathways such as defense signaling in plants. Some members may also contain additional domains, such as kelch repeats, which may contribute to substrate recognition.
HTH-type GbsR-related transcriptional regulator (HTH-GbsR_regulator)
Type: Family

This family of proteins includes transcriptional regulators that are involved in the response to environmental conditions such as osmolarity. They regulate the expression of operons related to the transport and metabolism of compounds like choline and glycine betaine, which are important for cellular adjustment to osmotic stress. Some family members act as repressors, binding to promoter regions and controlling gene expression in response to specific stimuli, while others are not responsive to such stimuli but still maintain regulatory roles over gene expression. The family is characterized by a helix-turn-helix (HTH) motif that facilitates DNA binding.
Lipopolysaccharide export system LptC (LPS_export_LptC)
Type: Family

This family of proteins is involved in the bacterial lipopolysaccharide (LPS) assembly pathway. Members of this family are essential for the translocation of LPS from the inner membrane to the outer membrane of Gram-negative bacteria. They act by facilitating the transfer of LPS to the periplasmic protein LptA and may serve as a docking site for LptA, playing a critical role in the integrity and function of the bacterial outer membrane.
Rubrerythrin (Rubrerythrin)
Type: Family

This family of proteins includes rubrerythrin from Porphyromonas gingivalis, Clostridium perfringens and related sequences from bacteria and archaea. Rubrerythrin is involved in cellular defense mechanisms against oxidative stress. Members of this family are known to catalyse the reduction of hydrogen peroxide, thereby protecting the cell from the damaging effects of reactive oxygen species . Some proteins within this family, such as rubrerythrin-1 from Clostridium acetobutylicum, function as part of an NADH peroxidase system, utilizing electron transport intermediaries to facilitate the reduction of hydrogen peroxide using NADH as an electron donor . The activity of certain family members is enhanced by the presence of rubredoxin, which acts as an electron-transfer shuttle in the catalytic process.
THEM4/THEM5 acyl-CoA thioesterase (THEM4/THEM5_acyl-CoA_thioest)
Type: Family

The THEM4/THEM5 thioesterase family is characterized by acyl-CoA thioesterase activity, specifically targeting medium and long-chain fatty acyl-CoA substrates, ranging from C14 to C18 in length. Members of the THEM4/THEM5 family are implicated in mitochondrial fatty acid metabolism, contributing to the regulation of energy production and lipid biosynthesis. Additionally, the family plays a role in the apoptotic process, with some members potentially influencing cell survival through the modulation of AKT1 activity. This regulation may involve either inhibition or enhancement of AKT1 phosphorylation and activity, which can affect its translocation to the plasma membrane and subsequent cellular signaling pathways.
GTP Pyrophosphokinase (GTP_Pyrophosphokinase)
Type: Family

This family of proteins functions as (p)ppGpp synthases, enzymes that are integral to the stringent response in eubacteria. Members of this family catalyze the synthesis of ppGpp (guanosine 3'-diphosphate 5'-diphosphate), a molecule that coordinates cellular activities in response to nutritional changes. These proteins can utilize GDP in place of GTP, enhancing (p)ppGpp production. The activity of these enzymes is highly cooperative and allosterically regulated by their products, with pppGpp being a particularly potent activator. The binding of pppGpp occurs in a regulatory cleft of the enzyme, influencing its activity. Although these proteins are structurally related to the RelA/SpoT family, they appear to play a secondary role in the stringent response mechanism.
Thiosulfate Sulfurtransferase/Rhodanese-like Domain-Containing Protein (Thiosulfate_ST/Rhodanese-like)
Type: Family

This family of proteins is involved in sulfur metabolism, specifically in the transfer of sulfur from donor molecules. Members of this family are known to catalyze the transfer of sulfur to various acceptor compounds, including cyanide and thiol compounds, forming products such as sulfite and thiocyanate. Some proteins within this family are thought to play a role in plant senescence processes. The activity of these proteins can be regulated by various factors, including the concentration of substrates and inhibitors such as thiosulfate, sulfite, and salts. The family includes proteins with rhodanese-like domains and thiosulfate sulfurtransferase activity, and some members are localized to the chloroplast.
2-oxoacid oxidoreductase subunit (2-oxoacid_oxidoreductase)
Type: Family

This family of proteins includes subunits of enzymes involved in the oxidative decarboxylation of 2-oxo acids to form corresponding acyl-CoA derivatives, a key step in various metabolic pathways. The enzymes are multisubunit complexes, and the family members act as catalytic subunits that bind substrates and cofactors, facilitating the redox reaction. These proteins are found in archaea and are involved in processes such as the citric acid cycle and branched-chain amino acid metabolism.
Unsaturated Glycosaminoglycan Hydrolases (UG_Glycosaminoglycan_Hydrolase)
Type: Family

This family of proteins includes enzymes that catalyze the hydrolysis of unsaturated glycosaminoglycans, such as hyaluronate, chondroitin, and heparin disaccharides. They are involved in the degradation of extracellular matrix components, which is a crucial process in various biological contexts, including cell invasion and tissue remodeling. Members of this family preferentially act on sulfated glycosaminoglycans and release specific unsaturated monosaccharides as products. Some family members are also involved in the degradation of ulvan, a major polysaccharide in green seaweed, by cleaving specific unsaturated sugar residues. The activity of these enzymes is known to be partially inhibited by divalent metal ions.
Meta-cleavage pathway hydrolase (Meta-cleavage_hydrolase)
Type: Family

This family of proteins includes enzymes that are involved in the bacterial meta-cleavage pathway, which is a part of the degradation process for phenylpropionic acid. Members of this family are responsible for catalyzing the cleavage of the C5-C6 bond in specific dienol ring fission products. They belong to the AB hydrolase superfamily and share a common enzymatic function related to the breakdown of complex organic molecules, playing a role in bacterial metabolism and the recycling of organic compounds.
Bacterioferritin-associated ferredoxin (BFD-associated_ferredoxin)
Type: Family

This family of proteins is involved in iron storage and mobilization, potentially acting as a redox and/or regulatory component. Members of this family are thought to interact with bacterioferritin (BFR) and may play a role in the transfer of iron to and from BFR or other iron-containing complexes, thus participating in iron homeostasis.
Inner Membrane Protein YpjD/HemX (YpjD/HemX)
Type: Family

The protein family includes inner membrane proteins named YpjD and a protein involved in HemL synthesis, HemX. The YpjD proteins are found in various strains of E. coli, suggesting a conserved role within these bacteria. HemX is required for the synthesis of HemL, indicating a function in heme biosynthesis. The uncharacterized protein YNR3_AZOBR, found in the nitrogen-fixing bacterium Azospirillum brasilense, may also share functional characteristics with the family. The exact functions of YpjD proteins are not specified, but their conservation implies a significant role in bacterial inner membrane processes. The family appears to be involved in essential cellular functions, possibly related to membrane integrity or transport and heme biosynthesis.
Gamma-glutamyl amide hydrolase (Gamma-glu_amide_hydrolase)
Type: Family

This family of proteins includes enzymes that are involved in the hydrolysis of gamma-glutamyl amide bonds in specific substrates. Members of this family play a role in the biosynthesis of ergothioneine, an important antioxidant that protects certain bacteria from oxidative stress. Ergothioneine acts as a redox buffer, safeguarding bacterial cells against redox stressors and antibiotics, which can lead to respiratory alterations and bioenergetic deficiencies impacting virulence. Additionally, some family members are implicated in the degradation of glutathione and other peptides containing a gamma-glu-X bond, suggesting a broader role in amino acid and peptide metabolism.
SERAC1 (SERAC1)
Type: Family

The SERAC1 family is implicated in essential biological processes involving lipid metabolism and intracellular trafficking. Members of this family are believed to play a crucial role in the remodeling of phosphatidylglycerol, a lipid component vital for mitochondrial functionality and cholesterol transport within cells. The proteins may execute a transacylation-acylation reaction to yield a specific phosphatidylglycerol species with a 36:1 fatty acyl composition. Additionally, they are potentially involved in the synthesis of bis(monoacylglycerol)phosphate, a lipid implicated in various cellular pathways.
Complex I 20 kDa subunit-like (Complex_I_20kDa-like)
Type: Family

This family of proteins includes subunits that are likely involved in redox reactions related to hydrogen metabolism. Members are thought to function in the coupling of redox reactions, involving ferredoxin and iron-sulfur (Fe-S) clusters, to proton translocation across membranes. This process is essential for conserving redox energy in the form of a proton gradient, which can be utilized for hydrogen production and various cellular energy-dependent processes. Some family members may act as components of hydrogenase complexes, which are enzymes that catalyze the reversible activation of hydrogen and can be involved in the formation of formate from hydrogen and CO2. The activity of these proteins can be modulated by metal ions such as copper.
Oxidative Scavengers and Glycosyltransferases (Oxidative_Scav/Glycosyltrans)
Type: Family

This family of proteins includes members with diverse functions, ranging from scavenging oxidative molecules to glycosyltransferase activity involved in the biosynthesis of heparan-sulfate. Some members are responsible for protecting cells by neutralizing harmful oxidative products, while others play a crucial role in the synthesis of heparan sulfate proteoglycans, which are essential for the movement of certain morphogens. These activities are critical for maintaining cellular homeostasis and proper developmental signaling pathways.
Mitochondrial enoyl-CoA hydratase domain-containing protein (Mitochondrial_ECH-domain)
Type: Family

This family of proteins is involved in the metabolic process of fatty acid biosynthesis, where they may contribute to the hydration of enoyl-CoA intermediates in the mitochondrial matrix. Additionally, these proteins are implicated in regulating insulin sensitivity, which is a critical aspect of glucose homeostasis in the body. The family is characterized by the presence of an enoyl-CoA hydratase domain, which is indicative of their role in the catalysis of the reversible hydration of 2-trans-enoyl-CoA to L-3-hydroxyacyl-CoA, a step in the beta-oxidation of fatty acids.
Nitrous-oxide reductase regulator (NosR_regulator)
Type: Family

This family of proteins includes transcriptional activators that are involved in the regulation of nitrous-oxide reductase genes, such as NosZ. Members of this family are responsible for initiating the transcription of genes that encode for enzymes involved in the reduction of nitrous oxide, a significant step in the denitrification process. Some proteins within this family are also similar to electron transport proteins, suggesting a role in electron transfer processes which may be related to their regulatory functions.
Type VII TA system RNase (Type_VII_TA_RNase)
Type: Family

This family of proteins includes RNases that are typically components of type VII toxin-antitoxin (TA) systems. These RNases are usually toxic when expressed alone, inhibiting cell growth by cleaving RNA molecules such as tRNA or mRNA, depending on the member. The toxicity is counteracted by cognate antitoxins, which neutralize the RNase activity through various modifications such as AMPylation. These systems are thought to play a role in maintaining plasmid stability and may be involved in bacterial stress responses or competition.
Viral DNA packaging terminase large subunit (Viral_DNA_packaging_terminase)
Type: Family

This family of proteins includes large terminase subunits that play a crucial role in the life cycle of certain viruses. These proteins function as ATP-driven molecular motors that facilitate the translocation of viral DNA into empty capsids. They also possess endonucleolytic activity, which is essential for initiating and terminating the packaging of viral DNA. The large terminase subunit works in conjunction with a smaller subunit that recognizes specific viral DNA sequences. Together, they form a complex with the portal protein, creating a packaging machine that cleaves the viral genome concatemer during the packaging process. After the DNA is encapsulated, the terminase complex is replaced by other proteins to complete the assembly of the viral particle.
AAA domain-containing protein (AAA_domain_protein)
Type: Family

This family of proteins is characterized by the presence of an AAA domain, which suggests a role in ATP-dependent processes. AAA domains are known to be involved in various cellular activities, including but not limited to, DNA replication, protein degradation, membrane fusion, and the regulation of other proteins' functions. Given the AAA domain's ability to bind and hydrolyze ATP, these proteins likely function as molecular motors or chaperones, facilitating conformational changes in proteins or the assembly/disassembly of protein complexes. The 'highly divergent' note indicates that while these proteins share a common domain, their specific functions may vary significantly from the canonical members of the AAA ATPase family.
Mitochondrial ABHD10 acyl-protein thioesterase (ABHD10_acyl-thioesterase)
Type: Family

This family of proteins functions as acyl-protein thioesterases, hydrolyzing fatty acids from acylated protein residues. They play a role in regulating mitochondrial antioxidant capacity by modulating the S-depalmitoylation of peroxiredoxin-5, a key antioxidant enzyme. Additionally, they are involved in the metabolic processing of mycophenolic acid acyl-glucuronide, an immunosuppressant drug metabolite, through deglucuronidation. These proteins are subject to inhibition by the compound palmostatin-B.
Anti-sigma-E factor RseA-like (Anti-sigma-E_RseA-like)
Type: Family

This family of proteins functions as anti-sigma factors for extracytoplasmic function (ECF) sigma factors, specifically sigma-E (RpoE). Members of this family regulate the activity of sigma-E by maintaining it in an inactive state until an extracytoplasmic signal induces a proteolytic cascade known as regulated intramembrane proteolysis (RIP). This cascade involves sequential cleavage by periplasmic and membrane-bound proteases, followed by cytoplasmic proteases, which ultimately degrade the anti-sigma factor and release sigma-E to initiate transcriptional responses to environmental stresses such as heat shock or acid stress. Some family members also interact with other proteins, such as RseB and SspB, which modulate their stability and degradation.
O-mannosyl-transferase TMTC (TMTC_O-mannosyltransferase)
Type: Family

This family of proteins includes O-mannosyl-transferases that are primarily involved in the post-translational modification of proteins by transferring mannosyl residues to the hydroxyl groups of serine or threonine residues. Members of this family have distinct roles, particularly in the modification of the cadherin superfamily, by adding O-linked mannose glycans at specific regions. Some members are also known to modify other proteins, such as PDIA3, indicating a broader substrate specificity within this family.
Obscurin and Obscurin-like Regulators (Obscurin/Obscurin-like_Reg)
Type: Family

This family of proteins includes structural components involved in myofibrillogenesis and the assembly of myosin into sarcomeric A bands in striated muscle. Members exhibit serine/threonine protein kinase activity, phosphorylating various substrates including N-cadherin and sodium/potassium-transporting ATPase subunits. They also bind to multiple forms of phosphatidylinositol phosphates, influencing the PI3K/AKT/mTOR signaling pathway and thereby contributing to the regulation of cardiomyocyte size and adhesion. Additionally, some members are core components of the 3M complex, which is essential for microtubule dynamics and genome integrity. They play a role in the ubiquitin ligase pathway, affecting Golgi morphogenesis and dendrite patterning in the brain, and are required for the localization of certain ubiquitin ligases to the Golgi apparatus in neurons.
G-protein-signaling modulator (GPSM)
Type: Family

The GPSM family includes guanine nucleotide dissociation inhibitors (GDIs) that regulate G-protein signaling independently of G protein-coupled receptors. Members of the GPSM family are involved in maintaining G(i/o) alpha subunits in their GDP-bound state, thus controlling heterotrimeric G-protein signaling. These proteins play crucial roles in mitotic spindle pole organization, cortical dynein-dynactin complex recruitment, and metaphase spindle orientation. They are also essential for asymmetric cell divisions in cerebral cortical progenitors and may influence macroautophagy in intestinal cells. Additionally, GPSM family members are implicated in drug addiction pathways.
Fibrocystin (Fibrocystin)
Type: Family

This family of proteins is involved in promoting ciliogenesis within renal epithelial cells, contributing to the formation of kidney tubules and maintaining the lumen architecture . They play a role in cellular symmetry, ensuring proper bipolar cell division by regulating centrosome duplication and mitotic spindle assembly . These proteins also maintain oriented cell division during tubular elongation via the planar cell polarity pathway. They are involved in epithelial cell morphogenesis, regulating cell-cell and cell-matrix adhesion, and participating in cell motility. They enhance cell-cell contact by positively regulating PTK2 kinase activity, which can lead to increased epithelial cell proliferation through HRAS/RAF1 pathways or decreased apoptosis via the PDK1/AKT1 pathway . Additionally, they may have roles in collecting-duct and biliary differentiation, as well as in the proliferation of cholangiocytes and the production of CCN2 in a CXCL8-dependent manner .
Peroxisomal trans-2-enoyl-CoA reductase (Peroxisomal_t2-enoyl-CoA_red)
Type: Family

This family of proteins is involved in the metabolic process of fatty acid chain elongation within peroxisomes. Members of this family are enzymes that specifically catalyze the reduction of trans-2-enoyl-CoA substrates with chain lengths ranging from C6 to C16, with the highest activity observed for the C10 substrate. These proteins do not exhibit 2,4-dienoyl-CoA reductase activity, indicating a specialized function in fatty acid metabolism. The enzymatic activity contributes to the biosynthesis of fatty acids by reducing the double bond of enoyl-CoA intermediates in a stereo-specific manner.
Secondary Metabolite Biosynthesis-Associated (Sec_Metab_Biosynth-Assoc)
Type: Family

This family of proteins includes enzymes involved in the biosynthesis of secondary metabolites such as glycolipid biosurfactants and reduced long-chain polyketides. Members of this family participate in complex gene clusters that mediate the production of specific bioactive compounds. These proteins are associated with the synthesis and modification of fatty acid-derived moieties that are subsequently linked to sugar residues or amino acids. Functions attributed to these proteins include hydroxylation of fatty acids, glycosylation, acetylation, and acylation processes, as well as the formation of amide bonds between fatty acyl substrates and amino acids. The biosynthetic pathways in which these proteins are involved lead to the production of molecules with potential antimicrobial properties and other bioactivities.
tRNA Nucleotidyltransferase/Poly(A) Polymerase (tRNA_nt/polyA_polymerase)
Type: Family

The tRNA nucleotidyltransferase/poly(A) polymerase family is involved in the synthesis of the tRNA CCA terminus, which is crucial for proper tRNA function and protein synthesis. Members of this family add the terminal adenosine residue to tRNA, and in some cases, can also add cytidine residues. The enzymes adopt a seahorse-like shape with distinct head, neck, body, and tail domains. While primarily functioning as tRNA nucleotidyltransferases, they do not act as poly(A) polymerases. The activity of these enzymes ensures the maturation and functionality of tRNA molecules by completing the CCA end, which is essential for amino acid attachment and subsequent translation.
E3 Ligase Complex Components and Neurotoxins (E3_Ligase-Neurotoxin)
Type: Family

This family of proteins includes components of E3 ubiquitin-protein ligase complexes and neurotoxins. Members involved in ubiquitination act as substrate recognition subunits in cullin-RING E3 ligase complexes, targeting specific proteins for proteasomal degradation, which is crucial for various cellular processes including cell cycle regulation and signal transduction. Other members are neurotoxins that modulate neurotransmitter release by binding to specific receptors and forming pores in the plasma membrane, affecting synaptic transmission. These toxins exhibit specificity for either vertebrate or insect cells and can induce neurotransmitter exocytosis through both pore formation and receptor-mediated signaling pathways.
Kelch repeat and BTB domain-containing protein (Kelch-BTB_domain-containing)
Type: Family

This family of proteins serves as substrate-specific adapters for BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complexes, which are involved in the ubiquitination and degradation of target proteins. Members of this family are characterized by the presence of kelch repeats and a BTB domain, which is responsible for mediating interactions with CUL3, a core component of the ligase complex. These proteins play a crucial role in various cellular processes, including mitotic progression and cytokinesis, by regulating the stability of specific proteins through ubiquitination. The kelch repeats may also be involved in protein-protein interactions, contributing to the specificity of substrate recognition.