SII-SWORD/CoKE huggingface dataset:
Iron-Sulfur Ferredoxin (Fe-S_Ferredoxin)
Type: Family

The protein family includes iron-sulfur proteins known as ferredoxins, which play a crucial role in electron transfer across various metabolic pathways. Ferredoxins typically contain iron-sulfur clusters that facilitate the transfer of electrons. Members of this family are involved in diverse processes such as methanogenesis, biosynthesis of coenzymes and archaeal membrane lipids, homocysteine biosynthesis, and the reduction of compounds like dihydromethanopterin. Some are also implicated in the maturation of other proteins, such as the periplasmic nitrate reductase subunit NapA. The versatility of the ferredoxin family reflects their fundamental importance in cellular redox reactions and energy metabolism across different organisms.
Succinate Dehydrogenase/Fumarate Reductase Iron-Sulfur (SDH/FRD_Iron-Sulfur)
Type: Family

The succinate dehydrogenase/fumarate reductase iron-sulfur protein family includes iron-sulfur protein (IP) subunits of succinate dehydrogenase (SDH) and fumarate reductase (FRD), which are involved in complex II of the mitochondrial electron transport chain. SDH subunits transfer electrons from succinate to ubiquinone (coenzyme Q) during aerobic metabolism, while FRD subunits catalyze the reduction of fumarate using various electron donors in anaerobic conditions. The family plays a crucial role in the interconversion of succinate and fumarate, contributing to cellular respiration and energy production.
HPF/YfiA ribosome-associated (HPF/YfiA_ribosome-assoc)
Type: Family

The HPF/YfiA ribosome-associated protein family is involved in the regulation of ribosome activity, particularly during stationary phase and under stress conditions. Members of the family promote the dimerization of active 70S ribosomes into inactive 100S ribosomes, which conserves energy when cell growth is not favored. Some members prevent 70S dimer formation, stabilizing ribosomes against dissociation, inhibiting translation initiation, and increasing translation accuracy. This regulation of ribosome activity is crucial for bacterial adaptation to environmental changes, ensuring efficient use of resources and survival during periods of stress or nutrient limitation. Additionally, certain members of the family have been implicated in the modulation of transcription and translation, as well as in immune responses by stimulating cytokine secretion through the TLR2 signaling pathway.
Bacterial microcompartment shell (BMC_shell)
Type: Family

This family of proteins is involved in the formation and function of bacterial microcompartments (BMCs), which are proteinaceous organelles that encapsulate enzymes and metabolic pathways. Members of this family form hexameric units that assemble into the shell of these compartments, controlling the selective diffusion of metabolites. They are essential for the structural integrity of BMCs and play a role in enhancing metabolic fluxes while protecting the cell from toxic intermediates. Some members are involved in the degradation of specific substrates, such as 1,2-propanediol or ethanolamine, by concentrating the required enzymes within the BMC. Others are associated with the carboxysome, a type of BMC that sequesters RuBisCO for carbon fixation in cyanobacteria and some chemoautotrophs.
Ciliary and flagellar integrity-associated protein (Cilia_flagella_integrity)
Type: Family

This family of proteins is involved in the structural and functional integrity of cilia and flagella, which are essential for cell motility and sensory functions. Members of this family participate in the assembly and regulation of dynein arms, which are motor protein complexes that drive the beating of cilia and flagella. They also contribute to the maintenance of the axoneme, the ciliary and flagellar skeleton, ensuring proper alignment and microtubule sliding. Additionally, some proteins in this family are implicated in the organization of the mitotic spindle and centrosome integrity during cell division, as well as in ciliogenesis regulation by preventing the formation of cilia through centriole capping.
MAPR/Neuferricin/Neudesin-like (MAPR/NEUFC/NENF-like)
Type: Family

This entry includes Membrane-associated progesterone receptor components (MAPR) such as PGRC1/2, Neuferricin, Neudesin and related proteins, which are involved in a variety of cellular functions related to heme-binding, lipid homeostasis, and membrane dynamics . PGRC2 also plays a role in adipocyte function and systemic glucose homeostasis . Members of this entry, despite lacking conserved iron-binding His residues in their heme-binding domains, are capable of binding heme and are implicated in processes such as neuronal differentiation in the case of neuferricin and neudesin , progesterone binding, heme homeostasis, and regulation of cytochrome P450 enzymes . They also act as intracellular heme chaperones and are involved in the maintenance of reproductive lifespan and systemic glucose homeostasis. Cytochrome P450 regulator dap1 from S. pombe, the orthologue of PGRC1/2, is required for sterol biosynthesis. It functions as a positive regulator of cytochrome P450 enzymes erg5 and erg11, a function that requires bound heme .
MARVEL domain-containing and chemokine-like factor proteins (MARVEL-CKLF_proteins)
Type: Family

This family of proteins includes members with a variety of functions related to cellular transport, immune regulation, and cell differentiation. Some proteins in this family are involved in vesicular trafficking, particularly in the cycling between the Golgi complex and the plasma membrane, which may be important for myelin biogenesis and function. Others act as regulators of immune checkpoints, specifically in the recycling and expression of PD-L1 on the cell surface, which is crucial for immune tolerance and antitumor immunity. Additionally, certain members have been implicated in cell differentiation within the intestinal epithelium. The family also contains proteins that may participate in ion transport by forming voltage-dependent, potassium-selective channels when incorporated into lipid bilayers.
Peripheral myelin protein 22/Epithelial membrane protein-like (PMP-22/EMP/MP20-like)
Type: Family

The PMP-22/EMP/MP20 family is involved in a variety of cellular processes including cell proliferation, cell-cell interactions, cell migration, and cell adhesion. Members of the family play crucial roles in the development and function of the nervous system, such as in myelinization and growth regulation. They are also key regulators of cell membrane composition, influencing protein surface expression and the formation of lipid rafts. Some family members are essential for immune responses, mediating cytotoxic degranulation of NK cells and CD8(+) T-cells, and activating CD4(+) T-cells. They contribute to cytolysis of target cells via the perforin/granzyme pathway and control cancer metastasis. Others are involved in lens development and cataractogenesis, acting as calmodulin receptors and contributing to junctional organization in lens fiber cells. The family also includes proteins that regulate angiogenesis and vasculogenesis, as well as embryonic development and cardiogenesis.
2H phosphoesterase superfamily YjcG-like protein (2H_phosphoesterase_YjcG-like)
Type: Family

This family of proteins is characterized by a conserved domain that suggests they have phosphoesterase activity, which is typically involved in the hydrolysis of phosphoester bonds. Members of this family are likely to participate in diverse biological processes, including the metabolism of nucleotides, lipids, and other small molecular compounds. The presence of a 2H motif, which usually contains two histidine residues, indicates a potential catalytic role in the cleavage of phosphate ester linkages. The exact biological functions may vary among different organisms and could be context-dependent, reflecting the diverse roles that phosphoesterases play in cellular metabolism and regulation.
Cysteine-rich repeat secretory protein (CRR_secretory_protein)
Type: Family

This family of proteins is characterized by the presence of cysteine-rich repeats, suggesting a potential role in protein-protein interactions or binding to specific ligands. These secretory proteins may be involved in various cellular processes, including defense mechanisms, signal transduction, or cell adhesion. The exact functions of these proteins can vary widely, but the common feature of cysteine-rich domains indicates a possible involvement in stabilizing protein structure through disulfide bond formation.
HAD-like hydrolase superfamily, SerB (HAD-like_SerB)
Type: Family

The SerB family is part of the HAD-like hydrolase superfamily and includes phosphoserine phosphatases that catalyze the dephosphorylation of O-phospho-L-serine to L-serine, an essential step in the biosynthesis of L-serine from carbohydrates. L-serine is utilized in protein synthesis, the production of other amino acids, nucleotide metabolism, and glutathione synthesis. It can also be racemized to D-serine, a neuromodulator. Some family members may act on O-phospho-D-serine and other substrates like phosphothreonine. The family is characterized by a conserved domain structure and enzymatic activity regulation by various factors, including metal ions and amino acids. Some members are implicated in virulence and may interact with host proteins to modulate the host immune response.
Mycobacterial A85 antigen (Mycobacterial_A85_antigen)
Type: Family

The mycobacterial A85 antigen family includes proteins that play a crucial role in the interaction of mycobacteria with host cells and the maintenance of cell wall integrity. Members of the family are involved in the high-affinity binding to fibronectin, a glycoprotein that facilitates the attachment of Mycobacterium tuberculosis to alveolar macrophages. They also participate in the synthesis of cell wall components by catalyzing the transfer of mycolic acids to arabinogalactan and the formation of trehalose dimycolate, also known as cord factor. Some family members exhibit diacylglycerol acyltransferase and mycolyltransferase activities, contributing to the biosynthesis of triacylglycerol and the cell wall's mycolic layer, respectively. The family's function is essential for the survival of mycobacteria, particularly under stress conditions, and is implicated in the pathogenesis of tuberculosis.
Cholesterol 7-desaturase (Cholesterol_7-desaturase)
Type: Family

The cholesterol 7-desaturase family is involved in the biosynthesis of steroid hormones by catalyzing the insertion of a double bond into the C7-C8 single bond of cholesterol, producing 7-dehydrocholesterol (7-DHC). This reaction is a crucial step in the synthesis of various steroid hormones, including Delta(7)-dafachronic acid, which is essential for processes such as insect molting, metamorphosis, and body growth. Members of the family are also key regulators of steroid biosynthesis in different organisms, playing significant roles in developmental pathways and physiological processes.
Xaa-Pro dipeptidyl-peptidase/Cocaine esterase (Xaa-Pro_dipeptidyl-ppase/CocE)
Type: Family

The protein family is characterized by enzymes that have a specific proteolytic function. Members of this family are known as Xaa-Pro dipeptidyl-peptidases, which are peptidases responsible for cleaving N-terminal dipeptides from polypeptides, particularly when the penultimate residue is proline. This enzymatic activity is essential for the sequential removal of unsubstituted N-terminal dipeptides from various polypeptides, contributing to protein maturation and degradation processes. Additionally, some family members are associated with the CocE/NonD hydrolase family, indicating a potential role in esterase activity, such as the hydrolysis of cocaine by cocaine esterase, which allows certain bacteria to utilize cocaine as a carbon and energy source. The family's functional diversity underscores its importance in both peptide processing and environmental adaptation.
CPA3 Na+/H+ Antiporter Subunit D (CPA3_Na-H_Antiporter_D)
Type: Family

This family of proteins includes antiporters that are involved in the exchange of sodium (Na+) and hydrogen (H+) ions across cell membranes. These antiporters play a crucial role in maintaining cellular ion homeostasis, particularly in the excretion of Na+ to adapt to high sodium environments or alkaline pH conditions. They function by utilizing a transmembrane electrical potential, which is inferred to be electrogenic, meaning that the transport process generates an electrical gradient. Some members of this family are also involved in the excretion of lithium (Li+) ions and do not transport potassium (K+), calcium (Ca2+), or magnesium (Mg2+). The activity of these proteins is essential for various physiological processes, including pH homeostasis, sodium resistance, and potentially in symbiotic nodule development during certain plant-microbe interactions.
GNT1/Glycosyltransferase 8 (GNT1/Glycosyltrans_8)
Type: Family

The GNT1/glycosyltransferase 8 family encompasses enzymes involved in the modification of glycans and the biosynthesis of oligosaccharides. Members of the GNT1 subfamily are N-acetylglucosaminyltransferases that participate in Golgi-specific N-linked glycan modification. The glycosyltransferase 8 subfamily includes galactinol synthases, which are key in synthesizing raffinose family oligosaccharides (RFOs) that serve as osmoprotectants under stress conditions. Glycogenins, another subfamily, initiate glycogen synthesis by self-glucosylating to form oligosaccharide primers for glycogen synthase. UDP-glucuronate:xylan alpha-glucuronosyltransferases contribute to cell wall biosynthesis by adding glucuronic acid branches to xylan. Inositol phosphorylceramide glucuronosyltransferase is essential for plant growth and defense. Collectively, the GNT1/glycosyltransferase 8 family plays diverse roles in cellular metabolism, stress response, and structural integrity across different organisms.
With No Lysine (K) Ser/Thr Protein Kinase (WNK_Ser-Thr_kinase)
Type: Family

The WNK kinase family is involved in the regulation of electrolyte homeostasis, blood pressure, and cellular responses to osmotic stress. They act as molecular sensors and regulators of ion transport in various tissues, including the kidney and nervous system. WNK kinases phosphorylate and modulate the activity of downstream kinases and ion cotransporters, influencing ion influx and efflux. Some family members are implicated in developmental processes, such as embryogenesis and flowering time modulation. They also participate in signaling pathways, like the Wnt and photoperiod pathways, and may have roles in subcellular trafficking. Certain members possess a kinase domain predicted to be catalytically inactive, suggesting additional regulatory or scaffolding functions independent of kinase activity.
Ikaros C2H2-type zinc-finger (Ikaros_C2H2-ZF)
Type: Family

The Ikaros C2H2-type zinc-finger protein family is characterized by its involvement in transcriptional regulation, particularly in the differentiation and maturation of lymphocytes. Members of this family, such as Ikaros, Aiolos, and Helios, play crucial roles in hematopoietic cell differentiation, B- and T-cell development, and apoptosis regulation. They bind to specific DNA consensus sequences, often containing a GGGA core, to modulate gene expression. The family includes transcriptional repressors and activators, with some members also involved in megakaryocyte differentiation. The N-terminal zinc-finger domains are typically responsible for DNA binding and targeting to specific genomic regions, while the C-terminal zinc-fingers mediate dimerization, essential for their function. The family's function is further modulated by isoform-specific interactions and the formation of complexes with other chromatin-remodeling proteins.
Exosome complex component Rrp42 subfamily (Exosome_comp_Rrp42_subfam)
Type: Family

The Rrp42 subfamily of the RNase PH family is comprised of non-catalytic components of the RNA exosome complex, which is essential for 3'->5' exoribonuclease activity. The family plays a significant role in RNA processing and degradation, contributing to the maturation of stable RNA species such as rRNA, snRNA, and snoRNA, as well as the elimination of RNA processing by-products and non-coding transcripts. In the nucleus, it helps limit the export of defective mRNAs to the cytoplasm. In the cytoplasm, it is involved in mRNA turnover, degrading unstable mRNAs with AU-rich elements and participating in RNA surveillance pathways to prevent translation of aberrant mRNAs. Members of the Rrp42 subfamily are also implicated in structuring the active site of other exosome components, such as Rrp41, and may be involved in Ig class switch recombination and somatic hypermutation.
Glycogen Synthase Kinase-3 (GSK-3)
Type: Family

The GSK-3 protein family is a group of constitutively active serine/threonine kinases that play key roles in various cellular processes, including glucose homeostasis, Wnt signaling, transcription factor regulation, and microtubule stability. Members of the family phosphorylate a range of substrates, leading to diverse outcomes such as the inhibition of glycogen synthesis, modulation of circadian rhythms, and regulation of cell differentiation and apoptosis. In Wnt signaling, they form complexes with other proteins to phosphorylate and regulate the stability of beta-catenin. They also contribute to the development of insulin resistance and are implicated in neurodegenerative diseases like Alzheimer's through the phosphorylation of tau protein. Additionally, they are involved in the regulation of autophagy, cell polarity, axon outgrowth, and stress responses. The activity of GSK-3 family members is regulated by phosphorylation and can be inhibited by lithium.
GDSL lipolytic enzyme (GDSL_lipolytic_enzyme)
Type: Family

The GDSL lipolytic enzyme family is characterized by a broad range of esterase and lipase activities, with members capable of hydrolyzing ester bonds in substrates with varying acyl chain lengths. These enzymes are known for their roles in plant development, pollen coat formation, and male fertility, as well as bacterial processes such as biofilm formation, cell motility, and rhamnolipid production. The family includes proteins with a C-terminal autotransporter domain that facilitates the translocation of the catalytic domain to the cell surface in bacteria. In plants, the family is involved in diverse biological functions, including lipid metabolism and plant defense. The GDSL motif, a conserved sequence within the enzymes, is integral to their catalytic function.
Lovastatin nonaketide synthase thioesterase (LovG)
Type: Family

The LovG family proteins are primarily involved in the biosynthesis of various secondary metabolites with diverse biological activities, including antihypercholesterolemic agents, mycotoxins, antifungal agents, and other bioactive compounds. Members of the LovG family typically function as esterases or hydrolases, catalyzing the release of covalently bound intermediates from polyketide synthases or non-ribosomal peptide synthetases during the biosynthetic pathways. These enzymes play crucial roles in the processing and maturation of complex natural products, often contributing to the structural diversity and bioactivity of the compounds. The family is named after the LovG enzyme involved in the biosynthesis of lovastatin, a well-known cholesterol-lowering drug.
Bacterial response regulator (Bact_response_regulator)
Type: Family

This family of proteins includes response regulators that are part of two-component signal transduction systems, which are typically involved in sensing environmental stimuli and regulating adaptive responses. Members of this family often contain a receiver domain that can be phosphorylated in response to signals detected by a sensor kinase. Once phosphorylated, these proteins can modulate various cellular processes, such as gene expression, chemotaxis, sporulation, and stress responses. Some proteins in this family act as transcriptional regulators, directly influencing the expression of genes related to specific adaptive responses. Others may interact with additional proteins, such as flagellar motor components, to affect cell motility. The functions of these proteins are critical for the survival and adaptation of bacteria to changing environmental conditions.
Aspartate/prephenate aminotransferase-like (AspAT/PAT-like)
Type: Family

The Class-I Pyridoxal-Phosphate-Dependent Aminotransferase family is characterised by its members' ability to catalyse the reversible transamination reactions involving various amino acids and keto acids. These enzymes typically utilize pyridoxal phosphate as a cofactor. This protein family includes bacterial Aspartate/prephenate aminotransferases that convert aspartate and 2-oxoglutarate to glutamate and oxaloacetate, with some members also able to transaminate prephenate . Other substrates like phenylalanine, tyrosine, tryptophan, and L-asparagine are also used by certain enzymes within the family. Some members exhibit specificity towards aromatic amino acids , while others participate in lysine catabolism or the biosynthesis of compounds such as methanofuran . This diversity reflects the family's involvement in various metabolic pathways, including amino acid biosynthesis, catabolism, and homeostasis.
Cytochrome c Oxidase Subunit (Cytochrome_c_Oxidase_Subunit)
Type: Family

The cytochrome c oxidase subunit family is involved in electron transport and energy conversion within the respiratory chain. Members of this family function as part of larger enzyme complexes, such as the cytochrome bc1 complex and the cbb3-type cytochrome c oxidase complex, which are essential for ATP synthesis. These proteins transfer electrons from donor cytochrome c via heme groups to other subunits within their respective complexes. This electron transfer is coupled with the generation of a proton gradient across the membrane, which is utilized for ATP production. Additionally, some family members act as electron acceptors for other enzymes, such as thiosulfate dehydrogenase and formate dehydrogenase, indicating a broader role in various electron transport chains.
Cellular Amino Acid Transporter (AminoAcid_Transporter)
Type: Family

The protein family is involved in the transport of amino acids across cellular membranes. Members of the family function as transporters or antiporters, often forming heterodimers with SLC3A2 or other proteins to mediate the exchange of amino acids. They can transport a variety of amino acids, including large neutral amino acids, cationic amino acids, and small neutral L- and D-amino acids. Some members are involved in the uptake of essential amino acids, thyroid hormones, and compounds like L-DOPA and methylmercury complexes, playing roles in nutrient absorption, neurotransmission, cellular signaling, and detoxification. The family includes transporters that participate in the regulation of mTORC1 signaling, glycinergic inhibitory neurotransmission, and nitric oxide synthesis. They are part of the amino acid-polyamine-organocation (APC) superfamily and the L-type amino acid transporter (LAT) family.