SII-SWORD/CoKE huggingface dataset:
NADPH Oxidase Activator (NCF2_NOXA1)
Type: Family

The NCF2/NOXA1 family comprises proteins that play a crucial role in the activation of NADPH oxidases, which are enzymes responsible for the production of superoxide and other reactive oxygen species (ROS). These ROS are involved in various biological processes, including host defense mechanisms, hormone biosynthesis, oxygen sensing, and signal transduction. Members of the NCF2/NOXA1 family typically contain domains such as OPR/PB1, SH3, and TPR repeats, which facilitate interactions with other proteins in the NADPH oxidase complex, such as NCF1, NCF4/p40-PHOX, and RAC1. The coordinated action of these proteins is essential for the activation of the latent NADPH oxidase complex, leading to the generation of superoxide, which is necessary for microbial killing and cellular signaling.
WD repeat-containing CDT2 adapter protein (WD-repeat_CDT2_adapter)
Type: Family

This family of proteins serves as substrate-specific adapters for DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes, which are crucial for cell cycle control, DNA damage response, and translesion DNA synthesis. Members of this family mediate the polyubiquitination and subsequent degradation of various substrates, including CDT1, CDKN1A/p21(CIP1), and others, often in response to DNA damage or during specific cell cycle phases to ensure proper DNA replication regulation. Interaction with PCNA via a PIP-box is typically required for substrate polyubiquitination. Some family members also contribute to the regulation of the circadian clock by targeting specific proteins for degradation.
Intracellular Signaling and Trafficking Protein (Intracell_Sig-Traffick_Protein)
Type: Family

This family of proteins is involved in intracellular signaling and trafficking processes. Members of this family play roles in the localization and trafficking of proteins from the plasma membrane to various intracellular compartments, such as recycling endosomes and the trans-Golgi network. Some proteins within this family contain a PX domain that mediates interaction with phosphatidylinositol 3-phosphate-enriched membranes, essential for their function in endosomal localization. Additionally, certain members are implicated in transmitting sphingosine-1 phosphate-mediated signaling and may participate in the recruitment of specific peroxiredoxins to early endosomes, suggesting a role in redox regulation and signal transduction.
Angiogenesis Inhibitor and Adhesion GPCR (Angio_Inhib/Adhesion_GPCR)
Type: Family

This family of proteins includes members that are involved in cell adhesion, cell-cell interactions, and angiogenesis inhibition. Some proteins in this family act as angiogenesis inhibitors, potentially influencing various angiogenesis processes. They may also function as orphan G-protein coupled receptors that activate transcription factors through specific signaling pathways, contributing to the regulation of angiogenesis. The family contains proteins with a C-terminal AMOP domain, which is important for their anti-angiogenic function. Additionally, receptor activity within this family is regulated by proteolytic processing, which can modulate the signaling activity of these proteins.
Zinc finger protein 346 and matrin-type protein 4 (ZN346_ZMAT4)
Type: Family

The Zinc finger protein 346 family is characterized by the presence of zinc-finger domains essential for binding to double-stranded RNA (dsRNA) and for nuclear localization. Members of this family show a preference for binding to dsRNA, although they can also interact with RNA-DNA hybrids. Some members have been reported to bind with low affinity to double-stranded DNA (dsDNA) and single-stranded RNA (ssRNA), and with high affinity to dsRNA without detectable sequence specificity. Additionally, certain members may have the ability to bind to specific microRNA (miRNA) hairpins. The functions of the Zinc finger matrin-type protein 4 within this family are not described in the provided information.
StAR-related Lipid Transfer (STARD3) (STARD3)
Type: Family

The STARD3 family includes sterol-binding proteins that facilitate cholesterol transport from the endoplasmic reticulum to endosomes. The transport is initiated by phosphorylation of an FFAT motif, which promotes membrane tethering. Family members act as lipid transfer proteins, redistributing sterol to endosomes at the expense of the cell membrane, and support membrane formation within endosomes. The START domain within these proteins is responsible for lipid transfer, featuring a hydrophobic cavity for lipid accommodation. The MENTAL domain anchors proteins to endosome membranes, allowing the START domain to interact with the cytosol. Some family members also bind other lipids, such as lutein. While primarily mediating cholesterol transport to endosomes, potential involvement in transport to other membranes like mitochondria has been suggested, pending further evidence. The family does not engage in transcriptional cholesterol sensing.
Elongin-A domain-containing protein (Elongin-A_domain)
Type: Family

This family of proteins functions as general transcription elongation factors known as elongin or SIII. They enhance the RNA polymerase II transcription elongation past sites that would otherwise arrest transcription. Members of this family are transcriptionally active, with some showing increased activity upon binding to the elongin BC complex. Additionally, certain members are involved in the ubiquitination process as part of a multisubunit complex, which includes the elongin BC complex and other proteins such as RBX1 and CUL5. This ubiquitination activity targets the monoubiquitinated RNA polymerase II subunit for proteolysis, playing a role in global genomic repair.
GMC Oxidoreductase-Related Enzymes (GMC_Oxidoreductase-Related)
Type: Family

This family of proteins is involved in diverse biological processes including cyanogenesis, which is the release of hydrogen cyanide (HCN) from injured tissues. Members of this family catalyze the stereospecific addition of HCN to various aldehydes. Some proteins within this family are major seed constituents and may serve as a storage form for reduced nitrogen. Others are implicated in the production of pigments or in the regulation of developmental processes such as post-genital organ fusion in flowers. Despite the varied functions, all members share a common feature of belonging to the GMC oxidoreductase family, suggesting a general role in redox reactions involving substrates like aldehydes.
Cytochrome b5/Flavoprotein Reductase (Cytochrome_b5/Flavoprotein_Rdt)
Type: Family

This family of proteins includes various members that are involved in electron transfer processes, particularly associated with the cytochrome b5 and flavoprotein pyridine nucleotide cytochrome reductase systems. They play roles in metabolic pathways such as the endoplasmic reticulum stress response pathway and protection against oxidative stress by reducing reactive oxygen species. Some members are involved in the biosynthesis of complex molecules, like the cyclic tetrapeptide apicidin F, and may also contribute to genomic integrity. Functions include NADH-cytochrome b5 reductase activity, involvement in lateral root formation, and resistance to certain platinum-based compounds.
Cell wall assembly regulator KNR4/SMI1 (KNR4/SMI1_regulator)
Type: Family

This family of proteins is involved in the regulation of cell wall assembly, particularly in the synthesis of 1,3-beta-glucan, which is a key component of the cell wall in various fungi. Members of this family may play a role in the transcriptional regulation of enzymes responsible for glucan and chitin synthesis, which are crucial for maintaining cell wall integrity and structure. Some proteins in this family are also implicated in the cellular response to nitrogen starvation and may influence the transition between different phases of the cell cycle, particularly the transition from quiescence to the G1 phase.
Immunoglobulin-like domain-containing protein LISCH7 (Ig-like_domain-LISCH7)
Type: Family

This family of proteins is involved in maintaining epithelial barrier function through the recruitment of MARVELD2/tricellulin to tricellular tight junctions, which is crucial for normal hearing and the survival of auditory neurosensory hair cells. Members of this family may also be implicated in lipid homeostasis, insulin secretion, and the regulation of alternative pre-mRNA splicing via binding to specific splicing factors. Additionally, they can function as B7-like molecules with T-cell inhibitory activity and may play a role in viral infections by modulating host-virus interactions. They are also associated with the clearance of triglyceride-rich lipoproteins from the blood, binding lipoproteins in the presence of free fatty acids for cellular uptake.
Calcineurin B homologous (Calcineurin_B_homologous)
Type: Family

The Calcineurin B homologous protein family is involved in a variety of cellular processes including cell pH regulation, vesicular trafficking, gene transcription, and signaling pathways. Members of this family function as cofactors that control plasma membrane-type Na(+)/H(+) exchange activity, thus influencing pH levels and cell survival under serum deprivation. They are involved in the stabilization and localization of the Na(+)/H(+) exchanger SLC9A1/NHE1 at the plasma membrane and can affect its pH sensitivity. Additionally, they play roles in the regulation of cell proliferation and tumor growth, and in the modulation of the calcineurin/NFAT signaling pathway, influencing transcription factor NFATC3 nuclear translocation and transcriptional activity. They also interact with microtubules and organelles of the endoplasmic reticulum and Golgi apparatus, and are implicated in the inhibition of ribosomal RNA transcription and kinase activity regulation.
Outer dynein arm-docking/Coiled-coil domain-containing protein (ODA-DC/CCD)
Type: Family

This family of proteins includes components of the outer dynein arm-docking complex (ODA-DC), which are crucial for the binding of outer dynein arms (ODA) onto doublet microtubules. Members are involved in the assembly of ODAs and their axonemal docking complex, facilitating the proper function of ciliary microtubules. Additionally, some family members play a role in spermiogenesis, contributing to the elongation of flagella and the formation of sperm heads, indicating a broader involvement in the development and function of motile cilia and flagella.
Centriole and Basal Body Structural Protein (Centriole_BasalBody_StrucProt)
Type: Family

This family of proteins is involved in the structural organization and biogenesis of microtubule-associated complexes. Members of this family play a crucial role in cytoskeletal organization, particularly in the formation and cohesion of centrioles and basal bodies, which are key components of the centrosome and cilia. They act as scaffolding proteins during early centriole biogenesis and are essential for the recruitment of various centriole satellite proteins and centriole-centriole cohesion during interphase. Some members are also implicated in meiosis and spermatogenesis, with additional functions such as regulating the nuclear localization of certain transcription factors. The presence of coiled-coil domains suggests that these proteins can form homodimers, which are important for their interaction with microtubules.
ZNRF ubiquitin-protein ligase (ZNRF_ubiq-protein_ligase)
Type: Family

The ZNRF ubiquitin-protein ligase family is characterized by its members' E3 ubiquitin ligase activity, which is crucial for various biological processes including neuronal transmission, plasticity, cell differentiation, and inflammation regulation. Members of this family ubiquitinate specific substrates such as the Na(+)/K(+) ATPase alpha-1 subunit and AKT1, influencing their endocytosis and degradation. This activity is essential for maintaining cellular functions and signaling pathways. The family's involvement in the regulation of mTORC1 activation and modulation of immune responses through TLR trafficking highlights its role in cellular homeostasis and response to external stimuli. The RING-type zinc finger domain present in these proteins is essential for their E3 ligase function.
C2H2-type Zinc Finger Maturation Protein (C2H2-ZF_Maturation_Protein)
Type: Family

This family of proteins is involved in the maturation of pre-60S ribosomal particles, specifically by promoting the nuclear export of the 60S ribosome. Members of this family are characterized by the presence of a C2H2-type zinc-finger domain, which is typically associated with DNA-binding activity. However, some family members are known to negatively modulate the DNA binding activity of other transcription factors, such as Oct-2, thereby influencing transcriptional regulatory processes. The proteins within this family are largely disordered except for the zinc finger domain, indicating a structured region that mediates their functional interactions.
G-protein Coupled Orphan Receptors (GPC_Orphan_Receptors)
Type: Family

This family of proteins includes G-protein coupled receptors (GPCRs) that are predominantly categorized as orphan receptors, which means their endogenous ligands are unknown. Members of this family are characterized by a significant level of constitutive activity, which is the ability to activate intracellular signaling pathways in the absence of a ligand. The signaling is primarily mediated through the G(s)-alpha protein, stimulating adenylate cyclase to increase intracellular cAMP levels. One member is identified as a high-affinity receptor for lysophosphatidic acid (LPA), indicating a role in mediating cellular responses to this lipid mediator. The family members are implicated in various functions, including potential roles in brain function and cellular signaling.
Copper transport ATOX1-like (Copper_transport_ATOX1-like)
Type: Family

This family of proteins is involved in the cellular transport of copper ions. Members of this family bind copper ions in the cytosol and deliver them to copper ATPase transport proteins, which are responsible for the distribution of copper to various cellular compartments and copper-dependent enzymes. The proteins contain a heavy-metal-associated domain that coordinates the copper ion through a conserved CXXC motif. The transfer of copper involves the formation of a heterodimer with the ATPase, where the copper ion is shared between the two proteins. This process is critical for maintaining copper homeostasis and protecting the cell against oxidative stress. Additionally, these proteins can interact with cisplatin, a chemotherapeutic drug, which can inhibit their copper-binding function.
ATF bZIP Transcription Factors (ATF_bZIP_TF)
Type: Family

The ATF bZIP family is involved in the unfolded protein response (UPR), a cellular stress response related to the endoplasmic reticulum (ER). Family members act as transcription factors that bind to ER stress response elements (ERSE) to activate UPR target genes during ER stress. They are synthesized as precursors embedded in the ER membrane and are processed upon ER stress, releasing their transcription factor form to translocate into the nucleus. The basic leucine-zipper domain is crucial for DNA binding and nuclear localization. Members of the family may also play roles in development, cone function in the retina, lifespan modulation, ER calcium homeostasis, and protection against proteotoxicity.
Aquaporin-11/12 water channel (AQP11/12_channel)
Type: Family

This family of proteins facilitates the transport of water and small neutral solutes across cell membranes, ensuring intracellular homeostasis in various organs such as the liver, kidney, and brain. Members of this family are involved in maintaining endoplasmic reticulum homeostasis, particularly under stress conditions, by regulating redox balance through the transport of hydrogen peroxide. This function is crucial for managing oxidative stress and maintaining an environment conducive to protein folding and translation within the endoplasmic reticulum. Additionally, these proteins play a role in kidney development and function, including the regulation of endosomal acidification in the proximal tubule. Some members may also be involved in the glycosylation processing of PKD1, which affects its membrane trafficking and prevents the accumulation of unfolded proteins in the endoplasmic reticulum.
Bis(5'-adenosyl)-triphosphatase activity regulators (Bis(5'-adenosyl)-TPase_reg)
Type: Family

This family of proteins is involved in the hydrolysis of dinucleoside polyphosphates, particularly those containing a purine base and at least three phosphate groups. The primary activity observed in these proteins is the cleavage of bis(5'-adenosyl)-triphosphates to produce AMP and ADP. This enzymatic function plays a role in regulating intracellular levels of dinucleoside polyphosphates, which can increase under stress conditions such as heat shock. Some members of the family also exhibit additional enzymatic activities, including hydrolysis of other nucleotide derivatives and modulation of various cellular processes such as apoptosis, cell proliferation, and survival signaling pathways.
Coiled-coil domain-containing protein involved in ciliogenesis (CC_CF)
Type: Family

This family of proteins includes components associated with centriolar satellites, which are crucial for primary cilium formation. The primary cilium is a microtubule-based organelle that extends from the surface of many vertebrate cells and is involved in signal transduction. The proteins in this family contain coiled-coil domains, which are known to facilitate protein-protein interactions. These interactions are essential for the assembly and stability of the centriolar satellites and thus play a significant role in the biogenesis of the primary cilium. The presence of these proteins in multiple species suggests a conserved function in ciliogenesis across different organisms.
Seed Development and Stress Response Regulator (Seed_Dev/Stress_Resp_Reg)
Type: Family

This family of proteins is involved in various aspects of plant development and stress responses. Members are known to regulate seed dormancy, germination, and maturation processes, often through interactions with abscisic acid signaling pathways. Some proteins in this family determine the temperature window for seed germination and influence the timing of flowering by modulating microRNA levels. Others are implicated in the formation of pollen surface apertures, which are crucial for pollen function and fertility. Additionally, certain family members act as regulators of abscisic acid sensitivity, affecting plant responses to environmental stresses such as salinity.
Glycosyl Hydrolase 18 Domain-Containing Protein (GH18_Domain-Containing)
Type: Family

This family of proteins includes enzymes that are primarily involved in the degradation of asparagine-linked glycoproteins. Members of this family exhibit glycosyl hydrolase activity, specifically targeting the hydrolysis of N-acetyl-beta-D-glucosamine (1-4)N-acetylglucosamine chitobiose core. This enzymatic action typically occurs at the reducing end of the bond and is contingent upon prior cleavage by another enzyme, glycosylasparaginase. Additionally, some members are implicated in the degradation of peptidoglycans during bacterial spore germination, recognizing specific muramic acid delta-lactam residues. The family is characterized by the presence of glycosyl hydrolase 18 domains, and some members also contain LysM domains, which are associated with peptidoglycan binding and substrate recognition.
UPF0148 domain-containing protein (UPF0148_domain)
Type: Family

This family of proteins is associated with a variety of cellular functions, including potential roles in mitosis and centromere association. Members of this family may have antigenic properties and could induce the production of anti-centromere antibodies. The precise functions of these proteins may vary among different organisms, and some members remain uncharacterized. The family is unified by a shared domain, indicating a potential common evolutionary origin and possibly conserved functional aspects.
Centrosomal protein 41 (CEP41)
Type: Family

This family of proteins is involved in the process of ciliogenesis, specifically in the post-translational modification of tubulin through glutamylation. Members of this family are implicated in the intracellular transport of tubulin polyglutamylases, such as TTLL6, from the basal body to the cilium. This modification is crucial for the proper function and structure of cilia. Although some members contain a rhodanese domain, they do not exhibit phosphatase activity, indicating that they are enzymatically inactive in this respect.
TBK1 and IKBKE adapter proteins (TBK1-IKBKE_adapters)
Type: Family

This family of proteins includes adapter molecules that play a crucial role in antiviral innate immunity. They are involved in the activation of serine/threonine-protein kinases TBK1 and IKBKE, which are key regulators of the immune response to viral infection. These proteins facilitate the oligomerization of TBK1 and enhance the phosphorylation of the NF-kappa-B p65 subunit RELA, leading to the activation of NF-kappa-B, a transcription factor important for the expression of immune response genes. Additionally, they are involved in the induction of interferon-beta (IFNB) promoter activation through the TICAM1 pathway and are essential for the induction of IRF-dependent transcription in response to viral infection.
LBX Family Transcription Factors (LBX_TF)
Type: Family

The LBX family of transcription factors is involved in various developmental processes. Members of the family are essential for the development of GABAergic interneurons in the spinal cord, migration and development of hypaxial muscle precursor cells for limb muscles, diaphragm, and hypoglossal cord. They regulate hypaxial muscle development by modulating the proliferation and differentiation of myoblasts. LBX factors are also implicated in embryonic axis formation, convergent extension movements, myofibril formation, and neuromast deposition during development. They achieve these roles by interacting with canonical and non-canonical Wnt signaling pathways, and by transcriptional regulation of genes specific to muscle development and cell migration.
Hydroxycarboxylic Acid Receptors (HCARs)
Type: Family

The Hydroxycarboxylic Acid Receptor family includes G-protein coupled receptors that mediate various physiological responses to hydroxycarboxylic acids, eicosanoids, and other ligands. Members of this family act as receptors for compounds such as L-lactate, nicotinic acid, (D)-beta-hydroxybutyrate, and 12-(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12-S-HETE). They are involved in processes such as anti-lipolysis, cell growth, inflammation, cancer promotion, and immune responses. Activation of these receptors can lead to signaling pathways involving inhibition of adenylyl cyclase, reduced cAMP levels, and activation of ERK1/2, MEK, and NF-kappa-B. Some receptors also play roles in apoptosis of mature neutrophils and in the regulation of adipocyte lipolysis. The family is characterized by its structural similarity to the G-protein coupled receptor 1 family and its ability to bind specific ligands with high affinity, mediating diverse biological effects.
Orthopedia Homeobox (OTP_Homeobox)
Type: Family

This family of proteins is primarily involved in the development and differentiation of neuroendocrine cells within the hypothalamus, as well as in the patterning of larval skeletal structures. Members of this family play crucial roles in the specification of various neuron types, including dopaminergic neurons in specific regions of the brain. Some proteins within this family are also implicated in the development of the central nervous system more broadly. They are characterized by belonging to the paired homeobox family, specifically the Bicoid subfamily, which suggests a function in transcriptional regulation during embryonic development.