SII-SWORD/CoKE huggingface dataset:
AP2-associated Ser/Thr protein kinase (AP2_assoc_SerThr_kinase)
Type: Family

The AP2-associated protein kinase family is involved in the regulation of clathrin-mediated endocytosis. Members of this family phosphorylate the AP2M1/mu2 subunit of the adaptor protein complex 2 (AP-2), enhancing AP-2's affinity for cargo membrane proteins during endocytosis initiation. They may preferentially phosphorylate threonine residues and also regulate the phosphorylation of other AP-2 subunits, AP-2 localization, and AP-2-mediated internalization of ligand complexes. Additionally, they phosphorylate NUMB, influencing its endosomal localization, and bind to NOTCH1, stabilizing its activated form and modulating its transcriptional activity. Some members are implicated in osteoblast differentiation, and others play a role in viral entry and lifecycle, including hepatitis C, Ebola, and Dengue viruses.
Intracellular Transport Effector (Intracell_Transport_Effector)
Type: Family

This family of proteins includes effectors involved in intracellular transport processes, particularly in the trafficking and stabilization of cellular components. Members of this family function as linkers that connect vesicles or organelles to motor proteins, facilitating their movement along cytoskeletal elements. Some proteins in this family are known to interact with Rab GTPases, which are critical regulators of vesicle trafficking. They may also participate in the anchoring of protein kinase A, serving as scaffolding proteins that bring together enzymes and substrates for efficient signal transduction. Additionally, certain members are implicated in the compaction and stabilization of the myelin sheath in oligodendrocytes by interacting with phospholipids in the cytoplasmic membrane.
Kelch domain-containing protein 8 (Kelch_domain_containing_8)
Type: Family

This family of proteins is involved in the final stages of cell division, specifically cytokinesis. Members of this family play a crucial role in ensuring the proper separation and distribution of chromosomes into daughter cells. They are essential for maintaining mitotic integrity, chromosomal stability, and preventing aneuploidy by protecting cells from mitotic errors and centrosomal amplification. These proteins are also implicated in the formation of the midbody structure, which is critical for the abscission process that physically separates the daughter cells at the end of cytokinesis.
Angiomotin-like (Angiomotin-like)
Type: Family

This family of proteins includes Angiomotin and related proteins. These proteins are involved in the regulation of cell polarity, proliferation, and migration, particularly in endothelial cells. They play a key role in angiogenesis and the maintenance of actin filament architecture . Angiomotin-like protein 2 inhibits the Wnt/beta-catenin signaling pathway by sequestering CTNNB1 to recycling endosomes, preventing its nuclear translocation . Additionally, they regulate the translocation of phosphorylated SRC to cell-matrix adhesion sites and selectively promote FGF-induced MAPK activation through SRC. These proteins are also implicated in tight junction maintenance and may interact with ARHGAP17 and angiostatin .
Tumor Necrosis Factor Ligand Superfamily (TNF_Ligand_Superfamily)
Type: Family

The protein family is part of the tumor necrosis factor superfamily, which includes cytokines involved in a wide range of biological processes such as cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. Members of this family are key players in the immune system and inflammatory response. They function as ligands that activate various receptors, including EDAR, EDA2R, TNFRSF13B/TACI, and TNFRSF17/BCMA, influencing cell signaling pathways like NF-kappa-B activation. They are involved in epithelial-mesenchymal signaling during the morphogenesis of ectodermal organs, regulation of tumor cell growth, angiogenesis, endothelial cell proliferation, and the regulation of humoral immunity. Some isoforms may also play roles in cell adhesion and have tumor suppressor activity. The family's involvement extends to the innate immune response and the melanization immune response, as well as the development of thermal allodynia following tissue damage.
PINc/VapC Toxin-Antitoxin RNase (PINc/VapC_TA_RNase)
Type: Family

The PINc/VapC protein family consists of toxic components of type II toxin-antitoxin (TA) systems. Members of this family function as ribonucleases (RNases) that can degrade RNA and inhibit translation, cell growth, and colony formation. These toxic effects are typically neutralized by coexpression with their cognate antitoxins, known as VapB proteins. The RNase activity of these proteins contributes to the regulation of cellular processes and stress responses, potentially by mediating the selective degradation of mRNA or other RNA species under certain conditions. The activity of some family members is known to be inhibited by EDTA, suggesting a dependence on divalent metal ions for their RNase function.
Trans-sulfuration enzymes (Trans-sulfuration_enzymes)
Type: Family

The trans-sulfuration enzymes family encompasses a group of enzymes involved in various biosynthetic pathways, including the production of amino acids and cyclic peptides. Some members of this family catalyze gamma-replacement reactions to form L-cystathionine from O-succinyl-L-homoserine and L-cysteine, or gamma-elimination reactions to produce 2-oxobutanoate, succinate, and ammonia . Some enzymes within this family participate in the biosynthesis of antibiotics and psychoactive metabolites, such as terminal alkyne-containing amino acids and the psychoactive compounds ibotenic acid and muscimol. Others are involved in the biosynthesis of unguisins, which are gamma-aminobutyric acid-containing fungal cyclic heptapeptides . The family also includes alanine racemases that contribute to the production of D-alanine, a component of nonribosomal peptide synthetase pathways.
Immunoreceptor signaling adapters (Immunoreceptor_sig_adapters)
Type: Family

This family of proteins includes adapters and linkers that play critical roles in immunoreceptor signaling pathways. They are involved in the regulation of signaling cascades downstream of various receptors such as T-cell antigen receptors, B-cell antigen receptors, and mast cell degranulation receptors. These proteins mediate interactions through SH2 domains and proline-rich regions, facilitating the activation of kinases, the mobilization of calcium, and the activation of transcription factors like NF-kappa-B and NFAT. They are essential for various cellular processes including cell development, activation, and apoptosis. Some members are also implicated in the negative regulation of natural killer cell-activating receptors and the production of interferon-gamma, as well as in promoting reactive oxidative species generation and necrosis.
Mitochondrial 2-oxodicarboxylate carrier (Mito_2-oxodicarb_carrier)
Type: Family

This family of proteins is involved in the transport of dicarboxylates and oxodicarboxylates across the inner mitochondrial membrane. Members of this family function through a counter-exchange mechanism, facilitating the import of key metabolic intermediates into the mitochondria. These substrates include 2-oxoadipate, 2-oxoglutarate, adipate, glutarate, and to a lesser extent, pimelate, 2-oxopimelate, 2-aminoadipate, oxaloacetate, and citrate. These transported molecules are central to the catabolism of amino acids such as lysine, hydroxylysine, and tryptophan. Once inside the mitochondria, these intermediates can be converted into acetyl-CoA, which then enters the citric acid cycle. This process is crucial for energy production and various biosynthetic pathways. The proteins in this family are characterized by their membership in the mitochondrial carrier family, indicating a shared structure and transport mechanism.
Retinoic acid-inducible GPCR family 3 (RA-inducible_GPCR3)
Type: Family

The G-protein coupled receptor 3 family is characterized by its members being retinoic acid-inducible G-protein coupled receptors, which suggests a potential interaction between retinoid and G-protein signaling pathways. Members of the family, such as Retinoic acid-induced protein 3, are implicated in modulating differentiation and maintaining epithelial cell homeostasis. They may also function as negative modulators of EGFR signaling and act as tumor suppressors in the lung. However, the exact functions of some members remain unknown, highlighting the family's role in diverse cellular processes and signaling mechanisms.
Immunoglobulin-like Cell Surface Receptor (Ig-like_CS_Receptor)
Type: Family

This family of proteins includes immunoglobulin-like cell surface receptors that are involved in various cellular processes such as negative regulation of receptor tyrosine kinase-coupled signaling, cell adhesion, neurite outgrowth, and immune responses. Members act as docking proteins, mediating translocation of phosphatases to the plasma membrane and participating in the formation of signaling complexes. They play roles in synaptogenesis, synaptic function, and the negative regulation of phagocytosis, mast cell activation, and dendritic cell activation. Some family members are involved in antiviral immunity by limiting virus internalization. They also interact with thrombospondins, which can stimulate phosphorylation and ROS production in response to external stimuli.
Centrosomal microtubule-associated protein (Centrosomal_MT-associated)
Type: Family

This family of proteins is involved in the organization and function of centrosomes, which are key structures for microtubule organization and spindle assembly during cell division. Members of this family are characterized by their ability to localize to centrosomes and to interact with microtubules, potentially forming ring-like structures around them. These proteins may play a role in tethering microtubules to centrosomes and kinetochores, and could be involved in the nucleation and bundling of microtubules. Additionally, some family members are implicated in the nuclear translocation and mitogenic activity of internalized growth factors, such as FGF2. The family is part of the broader translokin family, indicating a shared structural or functional domain that mediates their interactions with other proteins and cellular components.
Beta-galactoside alpha2-3 sialyltransferases (Beta-gal_alpha2-3_sialyltrans)
Type: Family

This family of proteins includes enzymes known as beta-galactoside alpha2-3 sialyltransferases, which are involved in the terminal sialylation of glycoproteins and glycolipids. These enzymes catalyze the transfer of sialic acid from the nucleotide sugar donor CMP-Neu5Ac onto acceptor substrates that terminate with Galbeta-(1->3)-GalNAc through an alpha2-3 linkage. The sialylation process is crucial for the biosynthesis of brain gangliosides, which are essential for myelin-associated glycoprotein (MAG) function, axonal myelin stability, and regeneration. Additionally, these enzymes participate in the regulation of CD8-positive T cell survival by sialylating core 1 O-glycans on T cell glycoproteins, thus preventing premature apoptosis and controlling memory T cell survival. They also contribute to the formation of specific gangliosides such as GD1a, GM1b, and GT1b, and sialylate pluripotent stem cell-associated antigens, forming structures like SSEA4.
Ethylene-responsive transcription factor ERF/AP2-like (ERF/AP2-like)
Type: Family

This family of proteins includes transcriptional activators that are involved in the regulation of gene expression in response to various stress factors. Members of this family are characterized by their ability to bind to specific DNA elements, such as the GCC-box pathogenesis-related promoter element and the DRE element, which are important for the activation of stress-related genes. These proteins play a significant role in plant responses to abiotic stress, such as drought, and are implicated in the regulation of stomatal closure movement under such conditions. The family belongs to the larger AP2/ERF superfamily, which is known for its involvement in a wide range of plant developmental processes and stress responses.
LIM and SH3 domain-containing protein (LIM-SH3_domain_protein)
Type: Family

This family of proteins is involved in the regulation of actin cytoskeleton dynamics. Members contain LIM and SH3 domains, which suggest roles in protein-protein interactions. These proteins are implicated in the assembly and maintenance of structures such as the Z-disk in muscle cells, as well as in focal adhesions. They are known to bind to actin, indicating a direct interaction with the cytoskeleton. Phosphorylation of these proteins can regulate their activity, which in turn affects actin-associated processes, including ion transport in various secretory epithelial cell types. The family's involvement in cytoskeletal activities is crucial for cellular structure and function.
Histone-lysine N-methyltransferase KMT5A (KMT5A)
Type: Family

This family of proteins includes N-lysine methyltransferases that specifically target 'Lys-20' of histone H4, marking it with a monomethyl group (H4K20me1). This modification is associated with epigenetic transcriptional repression and is particularly enriched during mitosis. These proteins are crucial for cell proliferation, as they contribute to the maintenance of DNA's higher-order structure and are involved in chromosome condensation and cytokinesis. Some family members also methylate non-histone proteins, such as p53, which influences gene expression regulation. Their activity is dependent on the SET domain, which is the site of enzymatic activity and requires flanking sequences for full functionality. They belong to a superfamily characterized by SAM-binding and are part of a histone-lysine methyltransferase subfamily.
MLP-like hydrophobic ligand-binding (MLP-like_ligand-binding)
Type: Family

This family of proteins includes members that are known to bind hydrophobic ligands, such as steroids, in vitro. The binding activity suggests a potential role in the interaction with or regulation of lipid-based molecules within the cell. The similarity annotations indicate that these proteins share common structural features, which may underlie their ligand-binding capabilities. However, the specific biological functions of most members within this family remain to be characterized in detail.
Upstream Binding Factor 1 (UBF1)
Type: Family

The UBF1 family proteins are primarily involved in the regulation of ribosomal RNA (rRNA) gene transcription. They recognize the rRNA gene promoter and activate transcription mediated by RNA polymerase I. This is achieved through cooperative interactions with the SL1/TIF-IB complex, to which they bind specifically at the upstream control element. Members of the UBF1 family are essential for the transcriptional regulation of ribosomal biogenesis, a critical process for cellular growth and proliferation. Some members of the family, such as those in mice, are also essential for the proliferation of certain cell types during early development. Additionally, a related protein in Caenorhabditis elegans is involved in mitochondrial DNA maintenance and may associate with telomeric DNA.
Copper Homeostasis Regulator (Copper_Homeo_Regul)
Type: Family

The Copper Homeostasis Regulator family comprises transcription factors that play crucial roles in copper ion sensing and homeostasis. Members of this family regulate the expression of genes involved in copper uptake, transport, and detoxification, particularly under varying copper concentration conditions. They activate transcription of copper transporters and metallothionein genes in response to copper scarcity, and some also regulate genes in response to oxidative stress or other metal ions. These proteins typically contain copper-binding domains that enable them to function as sensors of intracellular copper levels, binding to specific DNA sequences known as copper-responsive elements (CuREs) to modulate gene expression. The family's regulatory activities are essential for maintaining cellular copper levels, which is critical for various biological processes and for mitigating copper-induced toxicity.
Avidin/Streptavidin-related (Avidin/Streptavidin-rel)
Type: Family

This family of proteins is characterized by their ability to form strong non-covalent specific complexes with biotin, with one molecule of biotin binding per subunit. The exact biological function of these proteins is not fully understood, but their high affinity for biotin is a defining feature. The family includes both avidin and streptavidin types, which are known for their use in various biochemical applications due to this biotin-binding property.
Pleckstrin homology domain-containing family F (PH_domain-containing_F)
Type: Family

The Pleckstrin homology domain-containing family F is involved in various cellular processes including endosome fusion, receptor trafficking, fluid-phase transport, and apoptosis. Members of the family may enhance cellular sensitivity to TNF-induced apoptosis and play a role upstream of RAB5. The family's PH and FYVE domains are critical for localization to endosomes and the endoplasmic reticulum, and for initiating apoptosis through the lysosomal-mitochondrial pathway. This includes translocation to lysosomes, permeabilization of the lysosomal membrane, release of lysosomal enzymes, and alteration of mitochondrial membrane permeability, leading to caspase-independent cell death.
Thioredoxin domain-containing protein (TXND_domain-containing)
Type: Family

This family of proteins includes members that are suggested to play roles in the regulation of microtubule physiology and redox state regulation within cellular components such as dynein. Some proteins within this family are implicated in sperm tail maturation, potentially acting by modulating disulfide bonds during the final stages of development in the testis or epididymis. Despite containing domains related to the NDK family, certain members lack key residues for NDP kinase activity, indicating a divergence from the canonical enzymatic functions of NDK proteins.
Nucleoporin NUP42 domain-containing protein (Nucleoporin_NUP42)
Type: Family

This family of proteins is involved in nucleocytoplasmic transport, specifically in the export of mRNA from the nucleus to the cytoplasm. Members contain FG repeats, which serve as interaction sites for karyopherins, including importins and exportins. These repeats likely form an affinity gradient that guides transport proteins and their cargo through the nuclear pore complex (NPC) in a unidirectional manner. Some family members are also implicated in cellular processes such as cell polarity and may interact with viral proteins during infection.
Bacterial secretion system and toxin (Bact_secretion_toxin)
Type: Family

This family of proteins includes components of bacterial secretion systems and toxins involved in intercellular competition and biofilm formation. Members are implicated in the secretion of specific effector molecules, such as EsxA, and play roles in bacterial virulence, including abscess formation and persistence within host tissues. Some family members exhibit toxic activities, such as DNase or RNase functions, which target competitor bacteria. These toxic effects are often regulated by cognate immunity proteins, forming toxin-antitoxin pairs that protect the producing bacteria from self-intoxication. The toxins contribute to kin selection and spatial segregation in biofilms, potentially preventing conflict between bacterial strains cohabiting the same environment.
Forkhead box transcription regulator (Forkhead_box_regulator)
Type: Family

This family of proteins includes transcription factors characterized by a conserved forkhead domain. Members of this family are involved in the regulation of gene expression, particularly in the development and differentiation of various tissues. They act as transcription activators for lung-specific genes and play roles in smooth muscle differentiation during gut development. These proteins are also implicated in the proliferation of lateral plate mesoderm and are part of regulatory networks controlling visceral mesoderm development and midgut morphogenesis. They bind to specific DNA sequences to regulate the expression of target genes, which may include those involved in cell fate determination and tissue-specific functions.
FAM167 domain-containing protein (FAM167_domain)
Type: Family

This family of proteins is characterized by a shared domain indicative of a common evolutionary origin. Members of this family are involved in various cellular processes, although specific functions may vary among individual proteins. The presence of alanine and arginine-rich regions suggests potential roles in protein-protein interactions, nucleic acid binding, or regulation of gene expression. Some members are named FAM167, indicating a possible involvement in yet-to-be-determined familial or genetic functions. The uncharacterized proteins within this family suggest that there are aspects of their biological roles that remain to be elucidated through further research.
Gastrokine (Gastrokine)
Type: Family

The gastrokine family comprises proteins involved in the maintenance and integrity of the gastric mucosal epithelium. Members of this family exhibit mitogenic activity, suggesting a role in cell proliferation and tissue regeneration. Some gastrokines are also implicated in inhibiting gastric epithelial cell proliferation, indicating a potential regulatory function in gastric tissue homeostasis. The dual functions of gastrokines reflect their importance in balancing cell growth and maintaining the structure of the stomach lining, which is essential for proper digestive function.
XK-related membrane adapter (XK-related_adapter)
Type: Family

This family of proteins is involved in the intracellular transport of lipids. Members of this family function as membrane adapter proteins that facilitate the recruitment of the lipid transfer protein VPS13A from lipid droplets to the endoplasmic reticulum (ER) membrane. This recruitment is essential for the maintenance of lipid homeostasis within the cell and may play a role in various cellular processes that depend on lipid transfer and membrane dynamics.
Sperm-specific class P (Sperm-specific_class_P)
Type: Family

This family of proteins includes sperm-specific proteins that are likely involved in the process of spermatogenesis or the structural and functional properties of sperm cells. The proteins are designated as 'class P', which may suggest a particular class within a broader category of sperm-specific proteins. The exact functions of these proteins are not detailed in the provided information, but based on their names, they are presumed to be important for the reproductive biology of the organism from which they are derived, potentially playing roles in sperm motility, fertilization, or sperm-egg recognition.
Homeobox domain-containing protein (Homeobox_domain)
Type: Family

This family of proteins includes transcription factors characterized by a homeobox domain, which is a DNA-binding motif. They are involved in the regulation of gene expression, crucial for various developmental processes. Members of this family are known to bind specific DNA sequences to control the activity of target genes. Functions attributed to these proteins include the regulation of visual pigment gene clusters, zygotic genome activation, retinal neuron differentiation, and enteric muscle contraction. Some are essential for maintaining the differentiated state of retinal cells and may play roles in cellular differentiation in both sensory and nonsensory systems. The diversity of functions reflects the importance of these proteins in developmental biology and gene expression regulation.