SII-SWORD/CoKE huggingface dataset:
GPCR with Orphan and Phoenixin-Mediated Functions (GPCR_Orphan/Phoenixin)
Type: Family

This family of proteins includes G-protein coupled receptors (GPCRs) with diverse functions. Some members are orphan receptors, which are GPCRs with unknown endogenous ligands, and are potential candidates for amine-like GPCR activity. Other members are known to function as receptors for the SMIM20-derived peptides Phoenixin-14 and Phoenixin-20. These peptides are involved in the modulation of gonadotropin-releasing hormone (GNRH) signaling in the hypothalamus and pituitary gland, which is crucial for reproductive function. Additionally, in the ovary, certain family members mediate the proliferative effects of Phoenixin-14 and Phoenixin-20 on granulosa cells during follicular growth, indicating a role in ovarian function and fertility.
Superkiller complex protein 8 (SKI8)
Type: Family

The SKI8 family proteins are multifunctional components of both the PAF1 complex (PAF1C) and the SKI complex. In the PAF1C, they play a crucial role in transcriptional regulation by RNA polymerase II, influencing development, stem cell pluripotency, and hematopoiesis. They interact with the polymerase's CTD in both phosphorylated and non-phosphorylated forms, participating in transcriptional elongation, histone modification, and mRNA 3' end formation. SKI8 family proteins are implicated in ubiquitination of histone H2B and methylation of histone H3 on 'Lys-4' and 'Lys-79', affecting gene expression. Within the SKI complex, they assist in mRNA decay by extracting mRNA from ribosomes and directing it to the exosome for degradation. This function is crucial for mRNA quality control and the prevention of viral cytopathology. Additionally, some family members are involved in meiotic recombination and the regulation of flowering time in plants.
Mitochondrial Quality Control and Scaffold Kinases (MitoQC_Scaffold_Kinases)
Type: Family

The protein family includes both catalytically inactive kinases acting as scaffold proteins and active serine/threonine-protein kinases involved in mitochondrial quality control. The inactive kinases function as effectors of small GTPases, regulate cell morphology and motility, and coactivate Notch signaling. The active kinases protect against mitochondrial dysfunction by phosphorylating mitochondrial proteins, coordinating removal and replacement of damaged components, and facilitating mitophagy. They also regulate mitochondrial dynamics, promote mitochondrial fission, and are involved in mitochondrial biogenesis and localized repair.
Inactive Rhomboid (Inactive_Rhomboid)
Type: Family

The Inactive Rhomboid Protein family is characterized by members that regulate the ADAM17 protease, which is responsible for shedding epidermal growth factor (EGF) receptor ligands and TNF. Although members of this family are structurally related to peptidases, they do not exhibit proteolytic activity. Instead, they modulate various physiological processes including sleep, cell survival, proliferation, migration, and inflammation. Some family members indirectly activate the EGF receptor signaling pathway, further influencing these cellular functions.
Tectonin beta-propeller repeat-containing (Tectonin_beta-prop)
Type: Family

The Tectonin beta-propeller repeat-containing protein family is involved in a variety of biological processes including autophagy, bacterial recognition, and defense mechanisms. Members of the family act as tethering factors in autophagy, promoting autophagosome maturation and fusion with lysosomes, and are essential for phagophore and preautophagosomal structure biogenesis. Some proteins within the family bind to bacterial lipopolysaccharides and may participate in phagocytosis signaling. Additionally, the family includes pore-forming glycoproteins that can disrupt lipid bilayers, affecting the nervous and digestive systems of mammals, and may also play a role in meiosis and peroxisome biogenesis. The family is characterized by the presence of a PH domain that mediates binding to phosphatidylinositol-3-phosphate, and its members are known to interact with various cellular components such as the ATG5-ATG12 conjugate.
R-spondin domain-containing protein (R-spondin)
Type: Family

This family of proteins acts as activators of the canonical Wnt signaling pathway by serving as ligands for LGR4-6 receptors. They play a crucial role in various biological processes, including angiogenesis, embryonic development, and limb specification. By binding to their receptors, these proteins trigger the association of LGR4-6 with phosphorylated LRP6 and frizzled receptors, which are activated by extracellular Wnt receptors, leading to the activation of the Wnt signaling pathway and increased expression of target genes. Additionally, they regulate both the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling pathways. They can function independently of LGR4-6 receptors, potentially acting as antagonistic ligands to RNF43 and ZNRF3, which are important regulators of the Wnt signaling pathway. Furthermore, they may have roles in negatively regulating the TGF-beta pathway.
Immunity-related GTPase (IRG)
Type: Family

The IRG protein family is involved in innate immunity and inflammatory response, acting as dynamin-like GTPases that bind to intracellular membranes to promote their remodeling and trafficking. They play crucial roles in the clearance of acute protozoan and bacterial infections by interacting with autophagy and lysosomal proteins, facilitating the fusion of phagosomes with lysosomes for efficient degradation of pathogens. Additionally, they regulate selective autophagy, including xenophagy and mitophagy, and act as negative regulators of inflammatory and interferon responses by mediating autophagy-dependent degradation of inflammatory effectors and preventing the assembly of inflammasomes. They also participate in antiviral defense, mitochondrial quality control, and the preservation of hematopoietic stem cell function.
Histone-lysine N-methyltransferase SETDB (SETDB_methyltransferase)
Type: Family

This family of proteins includes histone-lysine N-methyltransferases that are primarily involved in the methylation of 'Lys-9' of histone H3, which is a key epigenetic mark for transcriptional repression. They recruit heterochromatin protein 1 (HP1) to methylated histones, thereby playing a central role in the regulation of gene expression during various biological processes such as oogenesis, embryonic development, and mitosis. These proteins are also implicated in the silencing of euchromatic genes, tumor suppressor genes, and in maintaining a repressive state of genes in embryonic stem cells. The methylation activity of these proteins is crucial for chromosome condensation and segregation, and they are involved in protecting genomic stability by suppressing transcription-induced replication stress.
Interferon-induced transmembrane antiviral protein (IFITM_antiviral_protein)
Type: Family

This family of proteins is involved in antiviral defense mechanisms, particularly by inhibiting the entry and fusion of various enveloped viruses with host cell membranes. They act by altering intracellular cholesterol homeostasis and preventing viral fusion with cholesterol-depleted endosomes. These proteins are also implicated in cell adhesion, growth, migration, and the antiproliferative action of interferon-gamma. Additionally, they play roles in bone mineralization and the structural stability and function of vacuolar ATPase, which is critical for acidifying phagocytic endosomes and establishing an antiviral state. They exhibit coordinated activity in hepatocytes to restrict certain viral infections by targeting virions for lysosomal degradation.
Plant Sucrose Phosphatase (Sucrose_Phosphatase)
Type: Family

The sucrose phosphatase family encompasses enzymes that catalyze the hydrolysis of sucrose-6-phosphate to produce sucrose and inorganic phosphate, representing the final step in the biosynthesis of sucrose. Members of this family are critical for sucrose metabolism in plants, playing a pivotal role in energy storage and transport. The activity of these enzymes is regulated by various factors, including metal ions such as zinc and chelating agents like EDTA. Some family members are specific for sucrose-6-phosphate and are inactive with other potential substrates such as fructose 6-phosphate.
PDE6D/unc-119 myristoyl-binding (PDE6D_unc-119_myristoyl-bd)
Type: Family

The PDE6D/unc-119 family consists of myristoyl-binding proteins that function as cargo adapters, specifically interacting with the myristoyl moiety of a subset of N-terminally myristoylated proteins to facilitate their correct localization. Members of the family adopt an immunoglobulin-like beta-sandwich fold with a hydrophobic cavity essential for myristate binding. The family plays a crucial role in various cellular processes, including synaptic functions in photoreceptor cells, signal transduction in immune cells, endosome recycling, bacterial uptake, endocytosis, protein trafficking in sensory neurons, and lipid-binding chaperone activity. They are also involved in G-protein localization and trafficking in sensory neurons, mediating Src family kinase signals for cytokinesis, and the localization of proteins to the primary cilium membrane.
Elbow/Noc Zinc Finger (Elbow/Noc_ZnFinger)
Type: Family

The Elbow/Noc family comprises zinc finger proteins that function predominantly as transcriptional corepressors, which do not directly bind DNA but may regulate transcription through recruitment of histone deacetylases to gene promoters. Members of the family are involved in various developmental processes, including the regulation of cell fate, cell adhesion, migration, proliferation, and differentiation. Specific roles have been identified in the development of sensory organs, neural plate border specification, hindbrain segmentation, and appendage formation. Some members may also function as transcriptional repressors and play roles in Notch signaling pathways, affecting cell proliferation and development of the supraesophageal ganglion, ocelli, and tracheal systems.
tRNA Modification and Golgi Maintenance Protein (tRNA_Mod/Golgi_Maint)
Type: Family

This family of proteins is involved in two distinct cellular functions. Some members are responsible for the post-transcriptional modification of tRNA molecules, specifically catalyzing the formation of 3-(3-amino-3-carboxypropyl)uridine at a specific position in the D-loop of cytoplasmic tRNAs. This modification is crucial for the proper functioning of tRNA during protein synthesis. Other members of the family are implicated in the structural maintenance of the Golgi apparatus, which is essential for protein sorting and trafficking within the cell. Additionally, these proteins may have a role in the process of hematopoiesis, the formation of blood cellular components.
Iron-sulfur cluster assembly LYR protein (ISC_assembly_LYR)
Type: Family

This family of proteins is involved in the biosynthesis of iron-sulfur (Fe-S) clusters, which are essential cofactors for a variety of cellular enzymes. Members of this family act as stabilizing factors in the core iron-sulfur cluster (ISC) assembly complex. They regulate the activity of the cysteine desulfurase NFS1, in association with NDUFAB1, and participate in the assembly of [2Fe-2S] clusters on the scaffold protein ISCU. This process involves the initial production of persulfide by the NFS1:LYRM4:NDUFAB1 complex, which is then delivered to ISCU. The assembly of the [2Fe-2S] cluster is further facilitated by FDX2, which provides reducing equivalents. Subsequently, the assembled [2Fe-2S] cluster is transferred to various chaperone proteins. These proteins may also play a role in iron-sulfur protein biogenesis in the cytoplasm.
KISH domain-containing protein (KISH_domain)
Type: Family

This family of proteins is involved in the early part of the secretory pathway. Members of this family are characterized by their role in the transport of proteins from the endoplasmic reticulum towards the Golgi apparatus, which is a critical step in the secretion of proteins and their delivery to their proper cellular destinations. The proteins within this family share a commonality in function across various species, indicating a conserved role in cellular physiology and the maintenance of proper protein distribution within the cell.
Betaine-homocysteine S-methyltransferase (BHMT)
Type: Family

This family of proteins is involved in the metabolic process of homocysteine regulation. Members of this family catalyze the transfer of a methyl group from betaine to homocysteine, resulting in the formation of dimethylglycine and methionine. This enzymatic activity is crucial for maintaining homocysteine levels within a narrow range, which is important for cardiovascular and neurological health. Additionally, the reaction mediated by these proteins is necessary for the irreversible oxidation of choline, a key step in the metabolism of this essential nutrient. Some family members utilize S-methylmethionine as a methyl donor instead of betaine, converting homocysteine directly to methionine. The activity of these enzymes can be modulated by various compounds, including dimethylglycine and methylthioacetate, which act as inhibitors.
DVL/RTFL regulatory polypeptides (DVL_RTFL_regulatory)
Type: Family

This family of proteins acts as regulatory molecules coordinating cellular responses essential for differentiation, growth, and development. They are involved in restricting polar cell proliferation in lateral organs such as leaves and petioles. Additionally, they play a role in coordinating the recruitment and differentiation of socket cells at trichome sites, which are hair-like projections on plant surfaces. These proteins are implicated in regulating positional cues and cell proliferation along the body axis.
Secreted Beta-Glucosidase SUN (Beta-Glucosidase_SUN)
Type: Family

The SUN family proteins are secreted beta-glucosidases involved in various cellular processes including aging, oxidative stress response, mitochondrial biogenesis, cytokinesis, cell wall biogenesis, and septation. They play roles in the host-pathogen interaction, adhesion to host tissue, and biofilm formation. Some family members are involved in mitophagy under nitrogen starvation, cell wall remodeling under different environmental conditions, and cell sensitivity to boric acid. They exhibit hydrolytic activity on linear (1->3)-beta-D-glucans and are implicated in the maintenance of kinase activity and mitochondrial expression of ATP synthase subunits.
Killer cell lectin-like receptor subfamily B (KLR_subfamily_B)
Type: Family

This family of proteins includes receptors that are primarily involved in the regulation of natural killer (NK) cell cytotoxicity. Members of this family can either stimulate or inhibit NK cell activity. Some proteins in this family contain an immunoreceptor tyrosine-based inhibitor motif (ITIM), which, upon phosphorylation, can bind SH2 domain-containing phosphatases, leading to the down-regulation of cell activation. Other family members are involved in the activation of NK cells or in the costimulation of T-cell proliferation and IL-2 production in response to antigen stimulation. These proteins may also play a role in 'missing-self' recognition, a process by which cells that do not express normal levels of major histocompatibility complex (MHC) molecules are targeted for attack by NK cells. Ligand binding to these receptors can also contribute to the formation of the immunological synapse between T-cells and antigen-presenting cells.
Keratin-associated protein type 19 (KRTAP_type_19)
Type: Family

The KRTAP type 19 family is involved in the structural integrity of hair. Members of this family are hair keratin-associated proteins (KRTAPs) that play a crucial role in the hair cortex. They are part of an interfilamentous matrix that embeds hair keratin intermediate filaments. These proteins contribute to the formation of a rigid and resistant hair shaft by facilitating extensive disulfide bond cross-linking with the cysteine residues of hair keratins. The matrix proteins are characterized by their high-sulfur and high-glycine-tyrosine content, which is essential for the mechanical strength and durability of hair.
Seed Storage Prolamin (Seed_Storage_Prolamin)
Type: Family

This family of proteins includes major seed storage prolamins, which are plant storage proteins primarily found in seeds. They are rich in proline and glutamine and are typically found in the endosperm of cereals. These proteins play a crucial role in the storage of nitrogen, carbon, and sulfur for the developing seedling. They are also involved in the formation of protein bodies during seed development and are important for the nutritional quality of the seed, as they are a source of amino acids for humans and animals. Members of this family are characterized by their solubility in alcohol-based solutions and their insolubility in water, which is a distinctive feature of prolamins.
Metabotropic Glutamate/GABA-B Receptor-like (mGluR/GABA-B-like)
Type: Family

This family of proteins includes metabotropic glutamate receptor-like proteins that are characterized by a dual domain architecture. The N-terminal section is similar to the BMP lipoprotein family, which may suggest a role in signaling or cellular communication. The C-terminal section is akin to the G-protein coupled receptor 3 family, specifically the GABA-B receptor subfamily, indicating a potential involvement in G-protein coupled receptor signaling pathways. These proteins may have functions related to development and differentiation, as suggested by annotations indicating a role in terminal differentiation and as a negative regulator during development.
N-acetyltransferase (N-acetyltransferase)
Type: Family

The acetyltransferase family is characterized by its ability to transfer acetyl groups from acetyl coenzyme A to various acceptor substrates. Members of this family, such as the RimJ subfamily, are involved in the post-translational modification of ribosomal proteins, specifically acetylating the N-terminal alanine of ribosomal protein uS5, which may play a role in ribosomal subunit maturation and function. Other members exhibit broader substrate specificity, catalyzing acetylation of peptide antibiotics, neurotransmitters, and components involved in siderophore biosynthesis, crucial for iron uptake and storage in certain fungi. The diverse functions of these enzymes reflect their importance in cellular processes ranging from protein synthesis to metabolic regulation and pathogenicity.
Diverse Ester Hydrolysis Enzymes (Ester_Hydrolysis_Enzymes)
Type: Family

This family of proteins includes enzymes with diverse ester hydrolysis capabilities. Members of this family are involved in the degradation of various substrates, including plant biomass components such as cellulose and xylan, as well as synthetic esters and triglycerides. Some proteins exhibit multifunctional esterase activities, acting as thioesterases, arylesterases, lysophospholipases, and proteases. They are characterized by their ability to cleave ester bonds, with some showing specificity for short-chain fatty acyl esters, and others for aromatic esters or acetyl groups on polysaccharides. The family includes enzymes that play roles in processes such as spore germination and intracellular survival. The presence of a dockerin-like region in one member suggests a potential role in multienzyme complexes for efficient substrate degradation.
O-antigen ligase-like (WaaL-like)
Type: Family

This entry represents O-antigen ligase from Escherichia coli (WaaL, ) and similar enzymes involved in the biosynthesis and modification of polysaccharides, such as O-antigens, which are components of lipopolysaccharides (LPS) on the outer membrane of Gram-negative bacteria.
CBASS antivirus and pafABC operon-associated protein (CBASS_pafABC_assoc_protein)
Type: Family

This family of proteins includes transcriptional regulators and proteins that are part of operons but are not directly involved in pupylation or substrate degradation. Some members function as DNA-binding transcriptional repressors in CBASS antivirus systems, which provide immunity against bacteriophage infections by synthesizing cyclic nucleotides that activate effectors leading to bacterial cell death. These proteins typically have an N-terminal winged HTH domain, a central WYL domain, and a C-terminal WCX domain, with the WYL domain forming swapped domains between subunits. Other members are part of the pafABC operon and are implicated in resistance to reactive nitrogen intermediates, although their exact roles in this process are not clear.
Bacterial siderophore ABC transporter ATP-binding (Siderophore_ABC-ATPase)
Type: Family

This family of proteins is involved in the transport of siderophores and iron complexes across cellular membranes. Members function as ATP-binding components of ABC transporter complexes, which are responsible for the energy-dependent uptake of various iron chelates, including hydroxamate and catecholate siderophores, as well as ferric citrate. These proteins are key for iron acquisition, a critical process for bacterial survival and pathogenicity, especially in iron-limited environments. They bind and hydrolyze ATP to provide the necessary energy for the translocation of their respective substrates through the transporter system.
Uracil-DNA glycosylase family, Type-4/5 (UDG_Type-4/5)
Type: Family

The Type-4 and Type-5 uracil-DNA glycosylase family consists of enzymes that play a crucial role in DNA repair by excising uracil from DNA. This occurs as a result of cytosine deamination or misincorporation of dUMP instead of dTMP. Members of the family can process uracil in various contexts, including double-stranded DNA with U/G, U/A, U/C, or U/T base pairs, and single-stranded DNA. Type-5 enzymes exhibit broader substrate specificity, capable of removing additional bases like hypoxanthine, xanthine, and 5'-modified uracils. Some members are regulated by product inhibition, with activity affected by the presence of AP-sites. Domain-specific features, such as the N-terminal region and pseudo-FCL region, contribute to protein stability, DNA binding, and catalysis.
DNA Adenine N(4)/N(6)-Methyltransferase (DNA_Adenine_Mtase)
Type: Family

The N(4)/N(6)-methyltransferase family is involved in the methylation of adenine residues within specific DNA sequences, which is crucial for the protection of genomic DNA from cleavage by restriction enzymes. Members of this family function as part of type I restriction-modification systems, which are composed of methyltransferase (MTase) and restriction endonuclease (R) subunits. These systems recognize specific DNA sequences and can act as molecular motors that translocate DNA in an ATP-dependent manner. The methylation activity of the MTase subunits modifies adenine residues to prevent DNA cleavage by the associated R subunit. The methylation pattern determines whether DNA is cleaved or further modified, with unmodified DNA being cut and hemimethylated DNA being fully methylated for protection. The family also includes type II methyltransferases that recognize and methylate specific DNA sequences to protect against endonuclease activity.
Acyl-CoA Synthetase/Transferase (Acyl-CoA_Synth/Transferase)
Type: Family

This family of proteins includes enzymes that catalyze the formation of acyl-CoA esters from various substrates, utilizing ATP and releasing ADP and phosphate. Members of this family are involved in central metabolic processes, such as the degradation of branched-chain amino acids and the conversion of acetyl-CoA to acetate. Some proteins within this family also exhibit acetyltransferase activity, modifying other proteins by acetylation, which can regulate their function. These enzymes play a role in responding to environmental changes by acetylating central metabolic enzymes. They are characterized by the presence of distinct domains that are evolutionarily related to the alpha and beta subunits of acetate CoA ligase, indicating a shared catalytic mechanism and structural features.