SII-SWORD/CoKE huggingface dataset:
Peroxisomal Beta-Oxidation Enzymes (Peroxisomal_Beta-Oxidation)
Type: Family

This family of proteins includes enzymes involved in the peroxisomal beta-oxidation pathway of fatty acids. Members exhibit multifunctional activities, such as hydratase, dehydrogenase, and epimerase, catalyzing the hydration of trans-2-enoyl-CoA to (3R)-3-hydroxyacyl-CoA and the subsequent dehydrogenation to 3-ketoacyl-CoA. These reactions are essential steps in the degradation of fatty acids, allowing for the breakdown of both straight-chain and branched-chain fatty acids, as well as bile acid intermediates. Some family members also participate in the metabolism of xenobiotic fatty acids and cholesterol side-chain degradation, highlighting the diversity of substrates and reactions these enzymes can perform. The presence of short-chain dehydrogenase/reductase (SDR) domains is a characteristic feature of this protein family.
Universal stress protein A (USP_A)
Type: Family

The universal stress protein A family comprises proteins that are implicated in the cellular response to various stress conditions. Members of this family are found across a wide range of organisms and are characterized by their ability to be upregulated during periods of environmental stress, such as exposure to heat, nutrient deprivation, or oxidative stress. These proteins are believed to play a role in protecting cells by maintaining cellular functions and by possibly participating in stress-related signaling pathways. The exact mechanisms by which universal stress proteins exert their protective effects are not fully understood, but they are thought to be involved in processes such as cell cycle regulation, protection of proteins from aggregation, and maintenance of ATP levels.
Sterol desaturase/TMEM195-like (Sterol_desaturase/TMEM195)
Type: Family

This family of proteins includes enzymes involved in lipid metabolism. Members of this family include Alkylglycerol monooxygenase (AGMO, also known as TMEM195) from animals, a glyceryl-ether monooxygenase that plays a role in cleaving the O-alkyl bond of ether lipids . These ether lipids are crucial components of brain membranes, indicating a significant role in the central nervous system . The family also encompasses enzymes such as C-5 sterol desaturases, which are implicated in sterol biosynthesis by introducing double bonds into sterols. Collectively, these proteins share structural similarities and are part of the broader sterol desaturase family.
PseI/Nans/NeuA/B acid synthases (PseI-like)
Type: Family

This entry represents related acid synthases such as PseI, Nans and NeuA/B proteins.

NeuB is the prokaryotic N-acetylneuraminic acid synthase. It catalyses the direct formation of N-acetylneuraminic acid (Neu5Ac), the most common sialic acid, by condensation of phosphoenolpyruvate (PEP) and N-acetylmannosamine (ManNAc). Mammals synthesise the 9-phosphate form, Neu5Ac-9-P, and utilise ManNAc-6-P instead of ManNAc . The bacterial and mammalian enzymes share 30%-40% sequence identity and are composed of two distinct domains. The N-terminal domain (NeuB domain,

) consists of ~250 amino acid residues, and is considered to bind the sugar substrates. The C-terminal domain consists of ~75 amino acid residues, and is called the antifreeze-like (AFL) domain, since it is similar to those observed in a variety of functional type III antifreeze proteins (AFPs) .
Metabolic Enzymes: Cyanogenesis, Opine Oxidation, G-3-P Dehydrogenation (Metab_Enz_Cyan_OpOx_G3PDH)
Type: Family

The protein family includes enzymes involved in distinct metabolic processes. One subgroup catalyzes the formation of hydrogen cyanide, a secondary metabolite, through a membrane-bound flavoenzyme system that transfers electrons to a cyanide-resistant branch of the aerobic respiratory chain. This process is regulated by various substrates and inhibitors and is oxygen-dependent. Another subgroup performs the oxidative cleavage of octopine into L-arginine and pyruvate. A third subgroup is responsible for the anaerobic conversion of glycerol 3-phosphate to dihydroxyacetone, using fumarate or nitrate as electron acceptors. The family encompasses proteins with diverse functions related to metabolism and electron transfer in various bacterial species.
Outer Membrane Porin-like (OMP-like)
Type: Family

This family of proteins includes major outer membrane components associated with peptidoglycans in various bacterial species. Members are believed to function as porins, which are proteins that form channels to allow the passive diffusion of small molecules across the outer membrane. Some proteins in this family have a C-terminal deletion, which may influence their structure and function compared to other members. The family is characterized by a conserved domain that suggests a shared evolutionary origin and functional similarity across different species.
UPF0046 metallophosphoesterase (UPF0046_metallophosphoest)
Type: Family

This family of proteins includes metallophosphoesterases that may exhibit activity in vitro. Members are suggested to play roles in the development of the nervous system and are known to be inhibited by nmolar levels of AMP and GMP. One outlier, a pectinolytic enzyme, does not belong to this family and is likely included in error.
Immunoregulatory Receptor-like (Immunoregulatory_rcpt-like)
Type: Family

This family of proteins includes both activating and inhibitory receptors that are widely involved in the regulation of the immune system. Members of this family are characterized by their ability to modulate cellular responses through interactions with cytoplasmic phosphatases and adapter molecules. They play roles in cellular signaling, with some acting as inhibitory receptors by recruiting phosphatases that dephosphorylate signaling molecules, thereby blocking signal transduction. Others act as activating receptors that associate with adapter molecules bearing immunoreceptor tyrosine-based activation motifs (ITAMs). These proteins are involved in processes such as immune cell regulation, target cell recognition, and activation of dendritic cells. They may also interact with viral proteins to modulate host immune responses.
Phosphoglycerate Mutase (Phosphoglycerate_Mutase)
Type: Family

The Phosphoglycerate Mutase Family is characterized by its broad range of phosphatase activities, including the hydrolysis of various phosphorylated substrates such as nucleoside tri- and diphosphates, phosphorylated organic acids, and amino acids. Members of this family, such as TIGAR, act as negative regulators of glycolysis by hydrolyzing fructose-2,6-bisphosphate and fructose-1,6-bisphosphate, leading to the activation of the pentose phosphate pathway and NADPH production. This activity is crucial for the regulation of intracellular reactive oxygen species, contributing to cell protection against oxidative or metabolic stress-induced cell death. Additionally, TIGAR plays roles in mitophagy inhibition, neuroprotection, cancer cell survival, and tissue regeneration. The family includes both metal-independent phosphatases and BPG-dependent PGAM subfamily members, indicating a diversity of enzymatic mechanisms and biological functions.
DENN Domain-Containing GEFs (DENN_Domain_GEFs)
Type: Family

The DENN domain-containing protein family functions as guanine nucleotide exchange factors (GEFs) that activate various RAB proteins, including RAB10 and RAB12, by promoting the exchange of GDP for GTP, thus converting them from an inactive to an active form. These proteins play crucial roles in cellular processes such as autophagy, vesicular trafficking, and maintenance of cell polarity. They are involved in the regulation of autophagy in response to starvation, protein transport from recycling endosomes to lysosomes, and insulin-stimulated glucose transporter delivery to the plasma membrane. Additionally, some family members are implicated in the development and maintenance of photoreceptor cells, cytokinesis, polarized cell expansion, and basal resistance against bacteria.
Patched domain-containing protein (Patched_domain-protein)
Type: Family

This family includes patched domain-containing proteins 1, 3, 4 from mammals and patched domain-containing proteins 9 and 18 from C.elegans.

PTCHD3 may play a role in sperm development or sperm function , however, it may not play an essential role in spermatogenesis or male fertility . PTCH1 is required for the development and function of the thalamic reticular nucleus (TRN), a part of the thalamus that is critical for thalamocortical transmission, generation of sleep rhythms, sensorimotor processing and attention . It can bind cholesterol in vitro . PTCHD4 may act as a repressor of canonical hedgehog signalling by antagonising the effects of SMO, as suggested by down-regulation of hedgehog target genes, including GLI1, PTCH1, and PTCH2 in PTCHD4-expressing cells . PTCHD18 is a transporter that promotes the endocytosis-mediated degradation of hedgehog-related proteins such as grl-7 in order to establish the capacity of progenitor cells to maintain quiescence in arrested L1 stage larvae .
Transposase 11-like (Transposase_11-like)
Type: Family

This family of proteins includes putative and inactive transposases, which are enzymes that catalyze the movement of DNA segments within the genome. These proteins often contain a characteristic H repeat motif and are typically associated with mobile genetic elements such as transposons. The members of this family are likely involved in the recombination and rearrangement of genetic material, contributing to genetic diversity and evolution. Some proteins in this family are annotated as inactive, suggesting that they may have lost their catalytic activity but could still play a role in binding DNA or in regulatory processes.
Rpn/YhgA-like nuclease (Rpn/YhgA-like_nuclease)
Type: Family

The Rpn/YhgA-like nuclease family comprises enzymes with low activity DNA endonuclease functions, primarily yielding 3'-hydroxyl ends. Members are involved in RecA-independent recombination and may play a significant role in horizontal gene transfer. Some family members enhance DNA recombination, which can lead to gene replacement in recipient DNA, while others are pseudogenes or inactive proteins. The active nucleases within the family can reduce cell viability and induce DNA damage, triggering the SOS repair response. Regulation of activity varies, with some inhibited by metal ions and others stimulated by Ca(2+) in the presence of Mg(2+). The family's involvement in generating crossover events suggests a role in the diversification of genetic material across different organisms.
STE20 Ser/Thr Protein Kinase (STE20_Ser-Thr_kinase)
Type: Family

The STE20 subfamily of serine/threonine kinases is involved in a variety of cellular processes including the response to environmental stress, cytokine signaling, and the regulation of actin cytoskeleton. Members of this family play key roles in developmental processes, such as embryogenesis, neuronal structure, and synaptic function. They act as upstream activators of pathways like the JUN N-terminal pathway and are essential for Wnt signaling, influencing gene expression and cytoskeletal rearrangements. Additionally, they participate in negative selection of thymocytes and may regulate cell migration, spreading, and dendrite arborization. This family includes kinases that phosphorylate targets such as cofilin-1, SMAD1, and TANC1, modulating actin polymerization, AMPA receptor trafficking, and stress-activated MAPK pathways.
Mitochondrial Outer Membrane Translocase MSP1 Subfamily (Mito_OM_Translocase_MSP1)
Type: Family

The MSP1 subfamily of the AAA ATPase family includes outer mitochondrial transmembrane helix translocases that are essential for the removal of mislocalized tail-anchored transmembrane proteins from the mitochondrion outer membrane. These proteins function as ATP-dependent dislocases, recognizing and binding tail-anchored transmembrane proteins to extract them from the membrane. Additionally, they play a crucial role in the regulation of AMPA receptor surface expression, impacting synaptic plasticity, learning, and memory. Some family members are involved in the ATP-dependent internalization of AMPA receptors and the inhibition of their recycling to the plasma membrane. The family also includes proteins that may be involved in intramitochondrial sorting and the regulation of translocase activity through interactions with other proteins such as PEX3.
SH3 domain-containing protein YSC84-like (SH3_domain_YSC84-like)
Type: Family

This family of proteins is involved in the organization of the actin cytoskeleton, fluid phase endocytosis, and vesicle trafficking. Members of this family contain an SH3 domain, which suggests a role in the interaction with proline-rich regions of other proteins, potentially mediating assembly of protein complexes involved in cytoskeletal organization and membrane dynamics.
NF-kappa-B Signaling Regulator (NF-kappa-B_Signaling_Reg)
Type: Family

This family of proteins is involved in the modulation of the host immune response. Members of this family are known to interact with components of the NF-kappa-B signaling pathway, specifically by recruiting the kinases IKKA/CHUK and IKBKB. Through this interaction, they are able to suppress the kinase activity towards NFKBIA, thereby negatively regulating the NF-kappa-B pathway. This function is critical in the context of viral infection, where the proteins are likely to contribute to immune evasion by the virus.
Flavin-dependent aromatic-ring hydroxylase (FAD_aromatic-hydroxylase)
Type: Family

This family of proteins includes flavin-dependent monooxygenases involved in various biological processes, including antibiotic resistance and biosynthesis of complex natural products. Members of this family catalyze the hydroxylation of aromatic rings, a reaction that typically requires FAD and NADPH as cofactors. These enzymes play roles in the inactivation of tetracycline antibiotics, contributing to antibiotic resistance, and are also involved in the biosynthesis of meroterpenoids with potential pharmacological activities, such as antitumor agents and inhibitors of the human GABAA receptor. The proteins contain a conserved N-terminal FAD-binding domain with a Rossman fold and a substrate-binding domain, which are essential for their monooxygenase activity.
Glutathionylspermidine Synthetase/Amidase (Gsp_Synthetase/Amidase)
Type: Family

This family of proteins includes enzymes that are primarily involved in the biosynthesis and hydrolysis of glutathionylspermidine (Gsp). Members of this family exhibit ligase activity, catalyzing the formation of an amide bond between glutathione (GSH) and spermidine with the concomitant hydrolysis of ATP. Some members also possess amidase activity, reversing the reaction by hydrolyzing Gsp back to GSH and spermidine. These activities are crucial for maintaining intracellular thiol redox balance and defending against oxidative stress. The family includes bifunctional enzymes with distinct domains for synthetase and amidase activities, which may be independently folded and functional. Some members are involved in the synthesis of trypanothione, a compound essential for the antioxidant defense in certain parasitic organisms. The family is characterized by a preATP-grasp domain in the C-terminal section, which is indicative of their enzymatic function.
Glycosyltransferase domain-containing protein (Glycosyltransferase_domain)
Type: Family

This family of proteins includes glycosyltransferases involved in various cellular processes such as vesicular trafficking, cell wall biogenesis, and synthesis of complex lipids. Members of this family are characterized by their ability to transfer sugar moieties from activated sugar donors to specific acceptor molecules, which can be proteins or lipids. Some proteins within this family have additional domains that confer specialized functions, such as binding to specific phospholipids or possessing additional enzymatic activities. These proteins play crucial roles in the modification of host cell processes during pathogen infection, the synthesis of cell wall components in fungi, and the regulation of cell morphology and membrane dynamics through the synthesis of mannosylated ceramides.
Phosphoinositide-Interacting Signal Transduction Regulators (PI-Interact_SigTrans_Reg)
Type: Family

This family of proteins includes adapters and regulators involved in signal transduction pathways. Members of this family are known to interact with phosphoinositides, specifically binding to certain phosphatidylinositol phosphates, which is crucial for their role in recruiting other proteins to the plasma membrane. These interactions are mediated by pleckstrin homology (PH) domains, which are common features among the family members. Some proteins in this family function as adapters in B-cell receptor signaling, while others are involved in coupling G proteins to adenylyl cyclase in response to extracellular signals. The precise functions of these proteins are essential for various cellular processes, including immune response and enzyme activation pathways.
Plant Aspartic Proteinase A1 (Plant_Aspart_Prot_A1)
Type: Family

The Aspartic Proteinase A1 family comprises extracellular proteases involved in diverse biological processes across various plant species. Members of this family are known for their role in nitrogen uptake through the digestion of prey in carnivorous plants, such as nepenthesin-1 and nepenthesin-2 found in pitcher fluid. In Arabidopsis thaliana, they participate in the regulation of endogenous sugar levels, influence plant morphology and development, and are implicated in the timing of tapetal programmed cell death critical for pollen development. Additionally, some members are involved in salicylic acid-dependent inducible resistance responses, potentially releasing peptide elicitors for the activation of resistance mechanisms. The family is characterized by a sensitivity to inhibition by pepstatin and related compounds, indicating a conserved mechanism of activity regulation.
Ubiquitin ligases and GTPase regulators (Ub-ligase/GTPase-reg)
Type: Family

This family of proteins includes E3 ubiquitin-protein ligases and GTPase regulators, which are involved in a variety of cellular processes. The E3 ubiquitin-protein ligases in this family are responsible for the transfer of ubiquitin from E2 ubiquitin-conjugating enzymes to specific substrate proteins, which can lead to their degradation, alter their cellular location, affect their activity, or promote protein-protein interactions. This ubiquitination is crucial for many cellular processes, including protein trafficking and sperm maturation. The GTPase regulators are involved in ciliogenesis, the formation and maintenance of cilia, which are essential for cell motility and signaling. They may also play roles in microtubule organization, transport within primary cilia, photoreceptor integrity, and spermatogenesis. Additionally, some members of this family are implicated in innate antiviral responses and regulation of responses to pathogens.
Phosphatase and SH3 domain-containing protein (Phosphatase_SH3-domain)
Type: Family

This family of proteins includes enzymes with phosphatase activity, particularly towards phosphorylated steroid compounds and protein tyrosine residues. Members are involved in the regulation of receptor-type tyrosine kinases, influencing cell surface receptor accumulation and down-regulation. Some proteins in this family exhibit tyrosine phosphatase activity towards a variety of substrates, including EGFR and ZAP70, and may also regulate proteins modified by ubiquitination. Additionally, certain family members have been shown to possess steroid phosphatase activity, catalyzing the conversion of inactive phosphorylated ecdysteroids into their active forms, which is essential for certain developmental processes. The family also includes proteins with SH3 domains that may interact with dynamin and potentially inhibit endocytic pathways.
Stress Response Regulator (Stress_Response_Reg)
Type: Family

This family of proteins includes transcription factors that are involved in various stress responses and metabolic processes. Members of this family are known to regulate gene expression in response to environmental stresses, such as oxidative stress, and are essential for the production of secondary metabolites like gliotoxin. They also play roles in the regulation of thiamine-repressible genes and are involved in the regulation of conjugation during meiosis. Some family members are necessary for growth on non-fermentative carbon sources and are implicated in hyphal formation in certain species. The proteins typically contain a C6 finger domain, which suggests a DNA-binding function, and they may recognize specific consensus motifs in the promoters of target genes.
Mono-ADP-ribosyltransferase and antiviral protein (ARTD-AVP)
Type: Family

This family of proteins includes enzymes with mono-ADP-ribosyltransferase activity, which modify target proteins by adding ADP-ribose, a process involved in various cellular functions including DNA repair, signal transduction, and stress responses. Some members act as negative regulators of transcription factors, such as the aryl hydrocarbon receptor (AHR), by mono-ADP-ribosylating these proteins, thereby inhibiting their transcriptional activity. Others are involved in nuclear envelope stability and nuclear remodeling during spermiogenesis. Additionally, certain members contain zinc finger domains and are implicated in antiviral responses by binding to viral RNAs and promoting their degradation, although these proteins possess a divergent PARP domain that is inactive due to the lack of structural requirements for NAD[+] binding.
T-cell Activation and Immune Regulation Protein (T-cell_Activation_Regulation)
Type: Family

This family of proteins is involved in the modulation of immune responses, particularly in T-cell activation and immune tolerance. Members of this family function as costimulatory molecules that are essential for T-cell proliferation, cytokine production, and the determination of T-cell fate regarding immunity or anergy. They interact with receptors such as CD28 and CTLA-4 on T-cells, influencing the activation threshold and effector responses. Some family members are ligands for the inhibitory receptor PDCD1/PD-1, playing a role in the maintenance of self-tolerance and limiting autoimmunity. They are also implicated in the immune escape of tumors by inhibiting cytotoxic T lymphocyte function. Additionally, certain members can act as transcription coactivators and are involved in signaling pathways such as NF-kappa-B activation. The family belongs to the immunoglobulin superfamily and includes proteins that may also interact with microbial agents, suggesting a role in infectious disease responses.
CCHC-type Zinc Finger Nucleic Acid Binding (Znf_CCHC_NABP)
Type: Family

The CNBP family proteins are characterized by their ability to bind nucleic acids through CCHC-type zinc finger domains. They predominantly bind single-stranded DNA and RNA, often with sequence specificity, such as the sterol regulatory element (SRE) sequence. Members of this family are involved in various cellular processes, including transcriptional repression, translation support by resolving G-quadruplex structures in mRNAs, and acting as transactivators for certain promoters like Myc. Some members may also play a role in sexual differentiation pathways. The family's functions are critical for maintaining proper gene expression and ensuring the stability and translation of mRNA by preventing the formation of secondary structures that could impede these processes.