SII-SWORD/CoKE huggingface dataset:
WWC/KIBRA Hippo Pathway Regulators (WWC/KIBRA_Hippo_Reg)
Type: Family

The WWC/KIBRA protein family consists of negative regulators of the Hippo signaling pathway, also known as the Salvador-Warts-Hippo (SWH) pathway. This pathway is crucial for organ size control and tumor suppression, as it restricts cell proliferation and promotes apoptosis through a kinase cascade. Family members, such as KIBRA, act synergistically with other proteins to regulate the pathway, leading to the phosphorylation and inactivation of the Yorkie (Yki) oncoprotein. Additionally, some members interact with transcription factors, like HD-ZIP IV, to influence cuticle development. The family also plays roles in cellular processes such as actin cytoskeleton organization, cytokinesis, and transcriptional coactivation. They are involved in cognitive functions, memory performance, and synaptic plasticity by regulating AMPA receptor trafficking.
RNA-binding and splicing regulatory protein (RNA-bind/splicing_reg)
Type: Family

This family of proteins includes factors involved in the regulation of RNA processing events, particularly pre-mRNA splicing. Members are characterized by their ability to bind RNA and sometimes DNA, often with a preference for single-stranded nucleic acids and specific purine-rich sequences. They play crucial roles in the assembly of spliceosomal complexes, interacting with both 5'- and 3'-splice sites and facilitating the ATP-dependent interactions of snRNPs with pre-mRNA. Some family members are also implicated in cellular responses to stress and may participate in RNA transcription or processing under such conditions. Additionally, certain proteins within this family are involved in cellular apoptosis pathways in response to specific treatments, such as cisplatin. The family also includes proteins that may contribute to the regulation of gene expression during development and in response to environmental stimuli, including pathogen attack and abiotic stresses.
Auxin Efflux Carrier (Auxin_Efflux_Carrier)
Type: Family

The Auxin Efflux Carrier family is involved in the transport and homeostasis of the plant hormone auxin, essential for plant growth and development. Members of this family act as components of the auxin efflux carrier system, mediating the formation of auxin gradients crucial for organogenesis, vein patterning, and root development. Some members are specifically involved in the intracellular auxin transport pathway, regulating auxin efflux from the endoplasmic reticulum into the cytoplasm, and are expressed in mutually exclusive domains of leaf vascular cells. They play roles in processes such as nectar production, unfolded protein response activation, gravitropic responses, and the establishment of the apical-basal axis in embryogenesis. The coordinated polar localization and recycling of these proteins are regulated by vesicle trafficking and phosphorylation, indicating a complex control of auxin transport dynamics.
Membrane-associated multiprotein complex regulator (MAM_complex_regulator)
Type: Family

This family of proteins is involved in the establishment and maintenance of the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells. They form membrane-associated multiprotein complexes that may regulate the delivery and recycling of proteins to their correct membrane domains. These proteins are known to interact with components such as CASK and APBA1, and are involved in the transport of vesicles containing specific receptor subunits along microtubules. They play a crucial role in synaptic vesicle exocytosis and cell adhesion in the brain, ensuring the proper localization of various receptors to neuronal postsynaptic densities. Additionally, they are required for the localization of certain channels and transporters to the basolateral membrane of epithelial cells, which may affect the amplitude of specific ion channel currents by stabilizing these channels at the cell surface.
Ly-6/neurotoxin-like and GPI-anchored (Ly-6/neurotoxin-like_GPI-ap)
Type: Family

The Ly-6/neurotoxin-like protein family includes GPI-anchored and secreted proteins that interact with nicotinic and muscarinic acetylcholine receptors (nAChRs and mAChRs), modulating their activity and affecting various physiological processes. Family members are involved in the regulation of T-lymphocyte proliferation, differentiation, and activation, as well as in the formation of the placenta by acting as receptors for syncytin-A. They play roles in lipid metabolism, cell proliferation, and maintaining the integrity of the skin. Some members have antitumor activities and are markers of late differentiation in the skin. The family also includes proteins that modulate nAChR trafficking, cell surface expression, and single channel properties, which can prevent excessive excitation and neurodegeneration. They are implicated in the regulation of plasticity in the primary visual cortex late in life.
Calcium-binding regulatory protein (Ca-binding_regulatory)
Type: Family

This family of proteins includes calcium-binding proteins that are involved in various cellular processes. Members of this family are characterized by their ability to bind calcium, which suggests a role as potential calcium sensors. Some proteins within this family are implicated in the negative regulation of Golgi-to-plasma membrane trafficking through interaction with PI4KB, thereby inhibiting its activity. This regulatory function may be important in neuronal physiology, potentially influencing memory and learning. Additionally, certain members are associated with store-operated Ca(2+) entry (SOCE), a mechanism that facilitates the influx of calcium into cells to replenish calcium stores. The presence of a C-terminal transmembrane domain in some family members indicates a role in membrane targeting.
Pre-mRNA-splicing factor CWC26 (CWC26_splicing_factor)
Type: Family

The CWC26 family comprises proteins involved in the pre-mRNA splicing process. Members of the CWC26 family are components of the spliceosome, a complex molecular machine that removes introns from a transcribed pre-mRNA segment. Specifically, some family members are implicated in the splicing of U12-type introns as part of the minor spliceosome. This function is essential for the accurate maturation of pre-mRNAs into mRNAs, which is a critical step in gene expression. In yeast, CWC26 family proteins are also associated with pre-mRNA nuclear retention and may play a role in bud site selection.
Integrator complex subunit 6 (Integrator_subunit6)
Type: Family

The Integrator subunit 6 family is involved in the transcription and 3'-box-dependent processing of small nuclear RNAs (snRNA), including U1, U2, U4, U5, and U7. Family members are components of the Integrator complex, which associates with the C-terminal domain of RNA polymerase II's largest subunit. They may also play a role in recruiting cytoplasmic dynein to the nuclear envelope. Additionally, some members may have tumor suppressor functions, as their ectopic expression can suppress tumor cell growth.
Mitochondrial RNA Processing CCM1 (Mito_RNA_Proc_CCM1)
Type: Family

The CCM1 family comprises RNA-binding proteins that play a crucial role in mitochondrial gene expression. Members of this family are involved in the specific removal of group I introns from mitochondrial encoded transcripts, which is essential for the correct processing of these RNAs. They also contribute to the stability of the small subunit mitochondrial 15S rRNA, thereby supporting the overall expression of the mitochondrial genome. Other family members, characterized by pentatricopeptide repeat motifs, are implicated in various aspects of RNA metabolism within organelles, suggesting a broad role in the regulation of gene expression at the post-transcriptional level.
Lysosomal-associated transmembrane transporter (LAPTM_transporter)
Type: Family

This family of proteins is involved in intracellular transport processes, particularly associated with lysosomal and endosomal membrane compartments. Members of this family may function in the translocation of nucleosides, nucleoside derivatives, and other essential amino acids across intracellular membranes. Some proteins within this family are implicated in the regulation of lysosomal function, including the sorting and degradation of epidermal growth factor receptor (EGFR), and the activation of mTORC1 signaling via the recruitment of specific solute carriers to the lysosome. Additionally, certain members bind to ceramide, facilitating its movement out of the late endosome, which may influence cell death pathways. Others may have roles in embryogenesis and hematopoietic cells, or act as negative regulators of transforming growth factor beta 1 (TGFB1) in regulatory T cells.
Cell Surface Receptors and Adhesion Molecules (Surface_Rcpt/Adhesion_Mol)
Type: Family

The protein family includes cell surface receptors and adhesion molecules with diverse roles in cell-cell interactions, signaling, and inflammatory responses. Members of the family mediate heterotypic and homotypic cell-cell contacts, often through interactions with specific ligands such as CD6 or laminin. They are involved in various physiological processes including T-cell activation, hematopoiesis, endothelial cell migration, and vascular tissue cohesion. Some members act as pattern recognition receptors, sensing stress signals and mediating pro-inflammatory responses through NF-kappa-B activation. They also play roles in neural development, tumor spread, and endothelial permeability. The family's involvement in pathfinding for axons and retinal ganglion cells highlights its significance in neural network formation.
T cell receptor gamma variable/constant region (TRG_var/const_region)
Type: Family

The T cell receptor gamma (TRG) family includes proteins involved in antigen recognition and the initiation of innate-like immune responses. TRG proteins are expressed on the surface of T cells, particularly gamma-delta T cells, which recognize self and foreign non-peptide antigens at epithelial boundaries. Antigen binding to TRG leads to phosphorylation of CD3 ITAMs, recruitment and activation of ZAP70, and subsequent signal transduction involving LCP2, LAT, and PLCG1. This cascade results in calcium mobilization, ERK activation, T cell proliferation, and differentiation. TRG diversity arises from somatic rearrangement of V, D, and J genes, with additional diversity from exonuclease trimming and random nucleotide additions during rearrangement. Some TRG members are non-functional due to altered recombination, splicing, or conserved amino acid changes.
Lateral signaling target protein 2 (LST-2)
Type: Family

This family of proteins acts as negative regulators of epidermal growth factor receptor (EGFR) signaling. Members of this family are involved in promoting the degradation of EGFR within endosomes. This regulatory activity is crucial for controlling the signaling pathways that influence cell proliferation and differentiation. Some proteins in this family contain a FYVE-type zinc finger domain, which is responsible for the interaction with phosphatidylinositol 3-phosphate (PI3P) and localization to early endosome membranes. This domain's function is contingent on the protein not being monoubiquitinated at a specific lysine residue.
Nematode serpentine receptor-like (Nematode_SR-like)
Type: Family

This family of proteins includes serpentine receptors, which are likely to function as G protein-coupled receptors (GPCRs). These receptors typically have a seven-transmembrane domain structure and are involved in signal transduction processes. They are known to play crucial roles in sensing environmental signals and initiating appropriate cellular responses. The diversity within this family suggests a broad range of ligands and functions, potentially including roles in chemosensation, development, and behavior in nematodes.
ABC Transporter, Amino Acid and LPS Transport (ABC_AA/LPS_Transport)
Type: Family

The protein family is involved in the transport of specific substrates across cellular membranes using ATP hydrolysis for energy. Members of the family function as components of ABC transporter complexes, which are critical for the translocation of substances such as branched-chain amino acids and lipopolysaccharides (LPS). The branched-chain amino acid transporters are high-affinity systems that facilitate the uptake of essential amino acids like leucine, isoleucine, and valine, and are also capable of transporting alanine and threonine. The LPS transporters are involved in moving LPS from the inner membrane to the outer membrane, a process essential for maintaining the integrity and function of the bacterial outer membrane. The family showcases the diversity of ABC transporters in facilitating the import and export of a variety of molecules, underscoring their role in cellular nutrition and defense.
Fumarylacetoacetate hydrolase (FAH)
Type: Family

The FAH family encompasses enzymes with diverse functions, including hydrolase activity and participation in various metabolic pathways. Members of the family are involved in the degradation of specific substrates such as ureidoglycolate, fumarylacetoacetate, and pentoses like D-xylose and D-arabinonate. These enzymes catalyze key reactions, such as the dehydratation of 2-dehydro-3-deoxy-D-xylonate into alpha-ketoglutarate semialdehyde and the conversion of D-arabinonate to 2-oxoglutarate. The family's name reflects its founding member, fumarylacetoacetate hydrolase, which plays a critical role in the tyrosine catabolism pathway. While some proteins within the FAH family are well-characterized, others are predicted to have hydrolase activity or remain uncharacterized, suggesting a potential for broader functional diversity.
SDR DHRS6-like (SDR_DHRS6-like)
Type: Family

This family of proteins includes enzymes that are part of the short-chain dehydrogenases/reductases (SDR) superfamily. Members of this family are involved in various metabolic processes, including the biosynthesis of secondary metabolites, fatty acids, and siderophores, as well as the detoxification of harmful compounds. They typically exhibit NAD(H) or NADP(H) dependent oxidoreductase activity, catalysing reactions such as the reduction of ketones to alcohols or the oxidation of alcohols to ketones. These enzymes play roles in the synthesis of complex natural products with potential pharmacological activities, regulation of iron transport and homeostasis, and conversion of cyclic substrates, which may include detoxification mechanisms.

This entry includes DHRS6, a cytosolic type 2 R-beta-hydroxybutyrate dehydrogenase belonging to the short chain dehydrogenase/reductase (SDR) family. DHRS6 catalyses the NAD-dependent conversion of (R)-hydroxybutyrate to acetoacetate. Found in humans and other vertebrates, DHRS6 is proposed to function in cytosolic ketone body utilisation during starvation or to generate precursors for lipid and sterol synthesis, complementing the mitochondrial type 1 R-beta-hydroxybutyrate dehydrogenase system. Its crystal structure reveals a tetrameric organisation with a classical SDR Rossmann fold .
Binding-Protein-Dependent Phosphate Transport Permease (Phosphate_Transport_Permease)
Type: Family

The phosphate transport system permease family is characterized by its role in the binding-protein-dependent transport system for phosphate. Members of this family are predominantly involved in the translocation of phosphate across the cellular membrane. They are typically part of larger ABC transporter complexes, which are essential for phosphate import in various bacterial species. The permease proteins facilitate the movement of phosphate ions through the membrane, contributing to the regulation of phosphate uptake and homeostasis within the cell. The family falls under the CysTW subfamily of binding-protein-dependent transport system permeases.
ABC-4 integral membrane protein family, HrtB subfamily (ABC-4/HrtB_transporter)
Type: Family

The ABC-4 integral membrane protein family, specifically the HrtB subfamily, is involved in the transport of hemin across the bacterial cell membrane. Members of the HrtB subfamily are part of the ABC transporter complex hrt, which is responsible for hemin import. These permease proteins facilitate the translocation of hemin, an iron-containing porphyrin, essential for various cellular processes. The family also includes uncharacterized ABC transporter permeases that are likely part of ABC transporter complexes and may be involved in the translocation of substrates across the membrane.
Thiosulfate sulfurtransferase domain-containing protein (Thiosulfate_sulfurtransferase)
Type: Family

This family of proteins is involved in sulfur metabolism, specifically in the transfer of sulfur from thiosulfate to other molecules. Members of this family typically contain two rhodanese domains, although only the C-terminal domain harbors the catalytic cysteine residue essential for activity. These proteins may function as sulfotransferases, facilitating the formation of thiosulfate, or in some cases, converting cyanide to thiocyanate, which is less toxic. This detoxification process is important for the survival of certain bacteria under cyanogenic conditions. Additionally, some members are implicated in the modification of tRNA molecules by contributing to the thiolation of specific uridine residues, which is a crucial post-transcriptional modification.
Fungal Secondary Metabolite Regulators (Fungal_SecMet_Regulators)
Type: Family

The protein family comprises transcription factors involved in the regulation of diverse biosynthetic gene clusters in fungi. Members of this family regulate the synthesis of secondary metabolites, including mycotoxins like patulin and oosporein, pigments such as pulcherrimin, and compounds with antimicrobial properties like sorbicillinoids and terreic acid. They also participate in the detoxification of plant-produced benzoxazolinones. These transcription factors typically bind to specific DNA motifs within the promoters of their target gene clusters, activating or repressing transcription in response to various environmental cues. Some members are also involved in yeast cell adherence, filamentous growth, biofilm formation, and drug resistance, indicating a role in fungal adaptation and virulence.
EgtD Methyltransferase Superfamily (EgtD_Methyltrsf_superfamily)
Type: Family

The EgtD family of methyltransferases is involved in the biosynthesis of various bioactive compounds, including ergothioneine, ergot alkaloids, and other peptide-derived alkaloids. Members of this family catalyze the S-adenosyl-L-methionine (SAM)-dependent methylation of specific amino acids, such as the triple methylation of the alpha-amino group of histidine to form hercynine, which is a precursor in the ergothioneine biosynthesis pathway. Additionally, they participate in the methylation of 4-dimethylallyl-L-tryptophan during the biosynthesis of ergot alkaloids, which are important for plant host fitness and have pharmaceutical applications. The family also includes enzymes involved in the biosynthesis of benzomalvin A and D, as well as imizoquins and other isoquinoline alkaloids that contribute to fungal defense and development.
Mitochondrial structure and function regulator (Mito_struct-func_regulator)
Type: Family

This family of proteins includes members that are involved in various cellular processes, primarily associated with mitochondrial function and structure. Some proteins within this family appear to play a crucial role in maintaining mitochondrial cristae formation and overall mitochondrial health. They may act in a kinase-independent manner to regulate key mitochondrial structural proteins, although their exact enzymatic activity remains unclear. Additionally, certain members are implicated in the degradation of cell wall material during cell separation, and others are involved in lipid homeostasis within mitochondria. There are also proteins in this family with potential roles in the biosynthesis of antibiotics and in plant immunity as effectors that suppress cell death.
NEK Ser/Thr protein kinase family, NIMA subfamily (NEK_Ser/Thr_kinase_NIMA)
Type: Family

The NEK Ser/Thr protein kinase family, part of the NIMA subfamily, is involved in various cellular processes including cell cycle regulation, DNA damage response, and cellular structure organization. Members of this family play crucial roles in centrosome separation, spindle formation, and chromosome condensation during mitosis and meiosis. They are also implicated in the G2/M checkpoint response to DNA damage by controlling the degradation of key cell cycle regulators. Some family members are essential for cilium assembly and may be involved in replicative senescence and DNA repair. The kinases typically phosphorylate threonine residues, although some also exhibit tyrosine kinase activity.
3'-5' Exonuclease domain-containing protein (3-5_Exonuclease_domain)
Type: Family

This family of proteins includes exonucleases with 3'-5' activity, acting on single-stranded and duplex DNA or RNA substrates. They play crucial roles in DNA replication, repair, and stability, as well as in mitochondrial metabolism and translation. Some members are involved in the RNA-induced silencing complex (RISC), influencing miRNA accumulation and plant development. The family is characterized by its ability to process overhang-containing duplexes, but not blunt-ended DNA. They are also implicated in the response to DNA damage and replicative stress, participating in double-strand break resection and homologous recombination, as well as in the stabilization and restart of stalled replication forks.
Adapter and Engulfment Domain-Containing Protein (Adapter_Engulfment-Domain)
Type: Family

This family of proteins includes various adapter proteins that play roles in cellular processes such as endocytosis, nitric oxide synthesis regulation, and phagocytosis of apoptotic cells. Members of this family are involved in the formation of protein complexes that are essential for specific functions at the cellular level, including synaptic functions and cellular transport. Some proteins in this family mediate interactions between enzymes and regulatory proteins, enhancing their activities. Others are involved in the internalization and trafficking of receptors and their ligands, contributing to cellular signaling and uptake of nutrients. The family also includes proteins that are necessary for the clearance of cellular debris and the restructuring of the cytoskeleton during developmental processes.
Protein Phosphatase PPP (PPP_phosphatase)
Type: Family

The PPP phosphatase family is involved in a variety of cellular processes including apoptosis, differentiation, DNA damage response, cell survival, regulation of ion channels, circadian rhythms, and phototransduction. Members of the family dephosphorylate a wide range of proteins such as kinases, nuclear receptors, SMAD proteins, and TAU/MAPT, influencing signaling pathways related to steroid and thyroid hormones, calcium, fatty acids, TGF-beta, oxidative and genotoxic stresses. They participate in DNA damage response mechanisms, checkpoint activation, and DNA damage repair. Some members regulate adipogenesis and circadian rhythms, while others are implicated in the regulation of the Hsp90 chaperone machinery and photoreceptor function. The family includes subfamilies such as PP-5 (PP-T) and PP-7, with some members possessing TPR repeats for protein-protein interactions and autoinhibition, or EF-hands for calcium activation.