SII-SWORD/CoKE huggingface dataset:
RAC1-specific guanine nucleotide exchange factor (RAC1-GEF)
Type: Family

This family of proteins includes guanine nucleotide exchange factors (GEFs) that specifically activate the GTPase RAC1, influencing various cellular processes. Members are involved in semaphorin signaling, which is critical for axonal guidance and neuronal development. They play significant roles in the assembly and disassembly of dendritic filopodia, spine formation, dendrite length regulation, and synapse formation. Some family members are implicated in the remodeling of the actin cytoskeleton, integrin signaling, cell adhesion, and osteoclast differentiation. Additionally, certain proteins within this family contribute to neurite development and the control of eye movement and gaze stability. A common feature is the presence of an intramolecular interaction between the DH domain and the PH domains, which can stabilize these proteins in an autoinhibited conformation, regulating their activity.
Kremen receptor (Kremen_rcpt)
Type: Family

This family of proteins includes receptors that interact with Dickkopf proteins to regulate Wnt/beta-catenin signaling. They are involved in promoting the endocytosis of Wnt receptors, such as LRP5 and LRP6, thereby inhibiting Wnt signaling. These proteins play a crucial role in limb development by ensuring normal limb patterning and can negatively regulate bone formation. Additionally, they have the ability to modulate cell fate decisions in the developing cochlea and can trigger apoptosis in a Wnt-independent manner, which is inhibited by the binding of their ligands. Some members of this family can also potentiate Wnt-beta-catenin signaling in the absence of Dickkopf proteins by maintaining Wnt receptors at the cell membrane.
Sorting Nexin/PX Domain-Containing Protein Kinase-Like (SortingNexin/PXDomain-PKLike)
Type: Family

The Sorting Nexin/PX Domain-Containing Protein Kinase-Like family is involved in various stages of intracellular trafficking, including protein transport from early to late endosomes and to the lysosome, potentially influencing the degradation of EGFR after EGF signaling. Members of the family may also play a role in the intracellular transport of viral nucleocapsids and modulate brain Na,K-ATPase subunits, impacting electrical excitability and synaptic transmission. Additionally, some members are associated with the regulation of calcium-activated channels, altering voltage sensitivity. The family includes proteins with a PX domain that interacts with phosphatidylinositol 3-phosphate enriched membranes, and some members are predicted to have an inactive protein kinase domain.
Intracellular mono-ADP-ribosyltransferase ARTD/PARP (ARTD_PARP)
Type: Family

The ARTD/PARP family comprises intracellular mono-ADP-ribosyltransferases involved in various cellular processes such as protein translation, stress responses, and unfolded protein response (UPR). Members of the family modify target proteins through mono-ADP-ribosylation, a post-translational modification that can regulate protein function and signaling pathways. Some family members, like PARP16, are known to inhibit protein translation by modifying ribosomal subunits, influence UPR by activating key effectors, and may be involved in cellular responses to amino acid starvation by promoting the formation of stress assemblies. The family is characterized by a conserved domain structure, including a regulatory PARP alpha-helical domain in some members, which can autoinhibit activity in the absence of specific signals.
Retinal determination transcriptional regulator (RD_transcriptional_regulator)
Type: Family

This family of proteins includes probable transcription factors involved in the retinal determination network. They play a role in the regulation of gene expression necessary for the induction and differentiation of specific sensory organ cells, such as the R8 photoreceptor cells in the eye. Members of this family are implicated in the repression and activation of other genes within the network, indicating a complex regulatory mechanism. They also contribute to the differentiation of antenna-specific characteristics in certain species, acting downstream of multiple genes that control the development of distal antennal structures. Additionally, some members are associated with transposition activities, suggesting a potential dual functionality or a distinct subgroup within the family.
NifX/NifY domain-containing protein (NifX/NifY_domain)
Type: Family

This family of proteins is involved in the processing of the iron-molybdenum cofactor, which is a critical component of the nitrogenase enzyme required for nitrogen fixation in certain bacteria. Members of this family are thought to play a role in the maturation or repair of the cofactor, ensuring the proper function of nitrogenase. The family includes proteins that share similarity, suggesting a conserved function related to nitrogenase activity.
Microtubule and Golgi organization protein (MT-Golgi_org_protein)
Type: Family

This family of proteins is involved in the organization and maintenance of cellular structures and processes. Members function in the formation and stabilization of microtubules, which are critical for mitotic spindle formation, chromosome alignment and segregation, and spindle pole establishment during cell division. Some proteins in this family act as golgins, which are thought to tether transport vesicles to the trans-Golgi network and regulate vesicular transport between endosomes and the Golgi apparatus. They may also be involved in the biogenesis of Golgi-associated microtubules. Additionally, certain members play roles in DNA damage response, primary cilia formation, epidermal differentiation, and hair follicle morphogenesis. The proteins typically contain coiled-coil domains and may interact with various phosphoinositides and other proteins to execute their functions.
Ribosomal subunit uS12 prolyl hydroxylase (uS12_prolyl_hydroxylase)
Type: Family

This family of proteins includes prolyl 3-hydroxylases and prolyl 3,4-dihydroxylases that are involved in the post-translational modification of the small ribosomal subunit protein uS12. The hydroxylation of a specific proline residue within uS12 is crucial for regulating the efficiency of protein translation termination. Some members of this family are also implicated in the formation of stress granules, which are involved in mRNA triage and cellular stress responses. The family is characterized by a shared evolutionary origin and is collectively referred to as the TPA1 family, indicating a conserved function across diverse species.
Monovalent cation:proton antiporter 1 (CPA1_transporter)
Type: Family

This family of proteins functions as electroneutral Na(+)/H(+) antiporters that exchange sodium or lithium ions for protons across cellular membranes. They utilize the proton gradient and membrane potential to extrude sodium, contributing to intracellular pH and sodium homeostasis. Members of this family are involved in various physiological processes, including renal tubular function, blood pressure regulation, insulin secretion, clathrin-mediated endocytosis in beta-cells, sperm motility, and fertility. Some members are sperm-specific and play a role in the pH regulation of spermatozoa. The activity of these proteins is allosterically regulated by their N-terminal domain and can be inhibited by compounds such as phloretin. There is some controversy regarding their role in osteoclast differentiation.
Sensory Perception USH2 Complex Protein (USH2_Complex_Protein)
Type: Family

This family of proteins is involved in sensory perception, particularly in hearing and vision. Members of this family play a crucial role in the formation and maintenance of the USH2 complex, which is essential for the proper function of hair cells in the inner ear. They are necessary for the elongation and maintenance of stereocilia, the mechanosensory structures on hair cells responsible for transducing sound vibrations into neural signals. In the retina, these proteins are required for maintaining the periciliary membrane complex, which is believed to be involved in intracellular protein transport. Additionally, some family members are part of the intermicrovillar adhesion complex, contributing to brush border differentiation and microvilli organization in the inner ear.
Zinc finger protein 385 (Znf385)
Type: Family

The Zinc finger protein 385 family is involved in various cellular processes, including apoptosis, mRNA localization and translation, cell cycle arrest, and differentiation. Members of this family may influence p53/TP53-mediated apoptosis and have roles in RNA-binding that affect mRNA translation and localization, such as with CEBPA and ITPR1 mRNAs. They are implicated in adipogenesis, neuron-specific functions, and may interact with ELAVL1 to control nuclear export of p53/TP53 mRNAs. Some family members can bind directly to p53/TP53, enhancing its role in cell-cycle arrest over apoptosis, and may also affect the ubiquitination and stability of CDKN1A. Additionally, they contribute to megakaryocyte differentiation.
SH2 domain-containing adapter proteins (SH2_domain_adapters)
Type: Family

This family of proteins includes SH2 domain-containing adapter proteins involved in various signal transduction pathways. They function as intermediaries that connect activated receptors to downstream signaling molecules. These proteins play crucial roles in processes such as angiogenesis, T-cell antigen receptor signaling, interleukin-2 signaling, apoptosis, and differentiation of neuronal cells. They are also implicated in the regulation of insulin signaling through IRS1 and IRS2. The SH2 domain within these proteins is known to bind phosphopeptides with a specific consensus sequence, facilitating interactions with a range of receptors and signaling proteins. Additionally, some family members may influence apoptosis in response to platelet-derived growth factor (PDGF). One member from Caenorhabditis elegans is involved in neuroblast migration during larval development.
RNA Processing and Spliceosome Component (RNA_proc/Spliceosome_comp)
Type: Family

This family of proteins includes members that are involved in various aspects of RNA processing, particularly pre-mRNA splicing. Some proteins in this family act as components of the spliceosome, a complex responsible for the removal of introns from pre-mRNA transcripts. They may participate in the assembly of the spliceosome or function within the activated spliceosome, contributing to the splicing of U12-type introns. Additionally, certain members are implicated in the retention of nuclear pre-mRNA and may influence the splicing of transcripts through the regulation of mRNA splicing factors. One member is specifically noted for its role in male sexual differentiation by regulating the mRNA splicing of sex determination genes.
Polygalacturonase-Inhibiting Protein (PGIP)
Type: Family

This family of proteins includes inhibitors of fungal polygalacturonase, which are key components in plant defense against phytopathogenic fungi. Members of this family are involved in the inhibition of a range of polygalacturonases from different fungal species, contributing to the plant's resistance mechanisms. Some members have been noted to have a preference for polygalacturonase from specific fungi, while others may not inhibit all polygalacturonases equally. Additionally, a member of this family is implicated in the regulation of floral organ number and another in promoting the flowering transition under long day conditions, indicating a role beyond pathogen resistance.
Glycosaminoglycan-degrading sulfatase (GAG-degrading_sulfatase)
Type: Family

This family of proteins includes enzymes with sulfatase activity, which are involved in the degradation of glycosaminoglycans such as chondroitin sulfate, dermatan sulfate, and heparan sulfate. They catalyze the hydrolysis of sulfate groups, particularly the 2-sulfate groups of the 2-O-sulfo-D-glucuronate residues. These enzymes exhibit a preference for heparan sulfate-derived structures and act selectively on 2-sulfoglucuronate, without activity against 2-sulfoiduronate. Their function is essential in various biological processes, including the persistence of gut symbionts in the gastrointestinal tract and the regulation of cellular signaling pathways mediated by sulfated molecules.
Polysaccharide Lyase Family 4 (Polysacch_Lyase_4)
Type: Family

The polysaccharide lyase 4 family comprises enzymes with pectinolytic activity, specifically targeting the rhamnogalacturonan I (RG-I) backbone of pectin. These enzymes are involved in the degradation of pectin, a complex plant polysaccharide, by cleaving the glycosidic linkages within the RG-I region. Pectin degradation is crucial for processes such as plant tissue maceration and pathogenesis in some plant pathogens, where these enzymes contribute to the rotting of plant tissues. The family includes enzymes that are active against various substrates, including linseed rhamnogalacturonan, and are essential for the full virulence of certain bacterial strains, as they facilitate the breakdown of plant cell walls.
EFR3 Homologs (EFR3_Homologs)
Type: Family

This family of proteins is involved in the regulation of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis. Members of this family are components of a complex that is required for the localization of phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. Within this complex, these proteins likely serve as the membrane-anchoring components. Additionally, they may play a role in cellular responsiveness to G-protein-coupled receptors, although the specifics of this function are not fully understood and may be indirect. Some members are essential for embryogenesis and cell viability.
Alpha-type Protein Kinase (Alpha-type_PK)
Type: Family

This family of proteins includes threonine kinases that play a role in regulating protein synthesis and myosin II filament assembly. Members are involved in phosphorylating specific threonine residues, which is crucial for controlling the rate of peptide chain elongation during protein synthesis or for the assembly and disassembly of myosin II filaments in various cellular processes. Some family members are capable of autophosphorylation, which is necessary for their enzymatic activity. The phosphorylation of target proteins by these kinases can render them inactive or alter their function, affecting processes such as cytokinesis, cell motility, and the localization of myosin during cellular events. The activity of some kinases in this family is regulated by calcium/calmodulin-dependent autophosphorylation, which can modulate their dependence on calcium/calmodulin.
Adapter protein with SH2 and Ras-GEF domains (SH2-Ras-GEF_adapter)
Type: Family

This family of proteins functions as adapter molecules in various signaling pathways, particularly those involving growth factor receptors. They are involved in promoting cellular processes such as proliferation, migration, and actin cytoskeleton reorganization. These proteins mediate the activation of MAPK signaling and DNA synthesis in response to insulin and other stimuli. They also play roles in cell adhesion by interacting with phosphorylated proteins and influencing integrin-mediated signaling. Additionally, they are implicated in the regulation of the cell cycle and may have a role in maintaining the structural integrity of the ocular lens. Some family members possess a guanine nucleotide exchange factor (GEF) activity for small GTPases, although this function is disputed in some studies. They also appear to be involved in the regulation of the immune response and the development of specific cell types.
Rho-type GTPase-activating protein (Rho-type_GAP)
Type: Family

This family of proteins includes GTPase-activating proteins (GAPs) primarily for the p21-rac subfamily of Rho GTPases. Members of this family are involved in the negative regulation of Rac by accelerating the hydrolysis of GTP to GDP, thereby inactivating the GTPase. This action is crucial for controlling various cellular processes such as cytoskeletal dynamics, cell migration, and axon guidance. Some members also function as phorbol ester receptors, linking extracellular signals to intracellular responses. The regulation of their activity is often mediated by phospholipid binding, which induces conformational changes that relieve steric inhibition of the active site, allowing for Rac binding and subsequent GAP activity. In neuronal systems, certain family members interact with EPHA4, playing a role in the assembly of locomotor circuits. Dysregulation of these proteins may contribute to the progression of certain tumors.
Eukaryotic initiation factor 2B subunit beta (eIF2B_beta_subunit)
Type: Family

This family of proteins functions as components of the translation initiation factor 2B (eIF2B) complex, which is responsible for the exchange of GDP for GTP on the eIF2 gamma subunit. This activity is crucial for the initiation of protein synthesis as it allows the formation of the eIF2-GTP-methionyl-initiator methionine tRNA complex necessary for the start of translation. The activity of these proteins is regulated by the phosphorylation status of the eIF2 alpha subunit; when eIF2 is phosphorylated, the exchange factor activity of the eIF2B complex is repressed, leading to a reduction in global protein synthesis. This serves as a regulatory mechanism during cellular stress responses. Some members of this family are also known to be activated by specific chemicals that can stimulate their activity regardless of the phosphorylation state of eIF2, thus influencing the integrated stress response.
Cell Surface Receptor and E3 Ligase Protein (CSR-E3_Ligase_Protein)
Type: Family

This family of proteins includes cell surface receptors and enzymes with roles in cellular fusion, differentiation, and immune system homeostasis. Members are involved in processes such as osteoclast bone resorption, osteoclastogenesis, and sperm-egg fusion during fertilization. Some proteins in this family function as E3 ubiquitin-protein ligases, mediating ubiquitination and subsequent proteasomal degradation of specific substrates, thereby regulating signaling pathways. Additionally, these proteins participate in the maintenance of immune self-tolerance and the regulation of antigen presentation by dendritic cells. Domains within these proteins are critical for their function, including interactions with other proteins and intracellular transport.
Asparagine synthetase domain-containing protein (Asn_synthetase_domain)
Type: Family

This family of proteins includes enzymes that are involved in the biosynthesis of the amino acid asparagine. Members of this family contain a domain that is responsible for the catalysis of the ATP-dependent conversion of aspartic acid to asparagine, a reaction that is critical for nitrogen metabolism and amino acid homeostasis in cells. These proteins are found across various species, indicating a conserved role in nitrogen assimilation and protein synthesis. The activity of these enzymes is essential for proper cellular function and development, as asparagine is a key amino acid in the synthesis of proteins and metabolic regulation.
WD repeat-containing GAD-1 (WD_repeat_GAD-1)
Type: Family

The WD repeat GAD-1 family is characterized by proteins that contain WD repeats, which are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his (GH) and tryptophan-aspartic acid (WD) dipeptides. Members of the family are involved in a variety of cellular processes through their role in the assembly of multi-protein complexes. The known function of one member is related to the initiation of gastrulation, a critical phase in embryonic development. However, the specific functions of other members within the family remain uncharacterized.
DDB1- and CUL4-associated factor (DCAF)
Type: Family

This family of proteins appears to be involved in ubiquitin-mediated proteolysis, acting as potential substrate receptors for the CUL4-DDB1 E3 ubiquitin-protein ligase complex. Some members are implicated in the regulation of lifespan and neuronal degeneration in response to metal stress. They may also interact with the transcription factor SKN-1 to modulate gene expression.
Plasmodium Circumsporozoite Invasion Protein (Plasmodium_CSP_Invasion)
Type: Family

This family of proteins is involved in the life cycle of the malaria parasite, Plasmodium. Members of this family play a crucial role in the parasite's ability to infect both mosquito vectors and vertebrate hosts. In the mosquito, these proteins are necessary for the development of sporozoites within the oocyst, their migration through the hemolymph, and their entry into the salivary glands. In the vertebrate host, they are essential for the sporozoites' migration through the dermis and subsequent invasion of hepatocytes. This is facilitated by the binding to highly sulfated heparan sulfate proteoglycans on the surface of host hepatocytes. The proteins exhibit two conformational states that are critical for their function: an adhesive state that allows for host cell invasion and a nonadhesive state that facilitates migration. Additionally, they possess a GPI-anchor for cell membrane localization and a domain that protects sporozoites from host antibodies.
NET actin-binding domain-containing protein (NET_actin-binding_domain)
Type: Family

This family of proteins is characterized by a plant-specific role in actin binding and association with various cellular structures. Members of this family are involved in forming membrane-cytoskeletal adapter complexes that may bridge the endoplasmic reticulum and the plasma membrane or associate with F-actin at the tonoplast, plasma membrane, and plasmodesmata. The presence of a NAB (NET actin-binding) domain suggests a common mechanism for F-actin binding across the family, which is essential for their function in cellular architecture and signaling.
Glycosyltransferase-like domain-containing protein 1 (GT-like_domain_containing_1)
Type: Family

This family of proteins is characterized by a glycosyltransferase-like domain. Members of this family are involved in the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. The activity of these enzymes is critical for the biosynthesis of complex carbohydrates and glycoconjugates. The glycosyltransferase group 1 to which these proteins belong suggests that they may have a common evolutionary origin and share structural features that are typical for this group. The Glycosyltransferase 4 subfamily indicates a more specific functional and structural categorization within the broader group, which may imply specialized roles in glycosylation processes.
Heavy metal-associated isoprenylated plant (HIPP)
Type: Family

The HIPP family comprises proteins that are likely involved in binding heavy metals. Members of this family are characterized by the presence of a heavy metal-associated domain, which suggests a role in the homeostasis or detoxification of heavy metals within the plant. These proteins are isoprenylated, which may influence their localization and interaction with other cellular components. The function of HIPP proteins in metal binding is indicated by the consistent annotation across multiple members, although the exact biological processes and metal specificity may vary among the family members.