SII-SWORD/CoKE huggingface dataset:
Saccharopine dehydrogenase-like oxidoreductase (Saccharopine_DH-like_oxidrdct)
Type: Family

This family of proteins is involved in the biosynthesis of complex lipids, specifically in the reduction of the double bond between C-4 and C-5 during the production of phthiocerol dimycocerosates (DIM A) and glycosylated phenolphthiocerol dimycocerosates (PGL). These compounds are significant components of the cell wall of certain bacteria and play a role in modulating the host immune response during infection. Members of this family exhibit oxidoreductase activity, catalyzing the NAD(P)H-dependent reduction of enoyl substrates within the lipid biosynthesis pathway.
SEZ6/CSMD/C4BPB Neuronal & Immune Regulators (SEZ6_CSMD_C4BPB_Regulators)
Type: Family

The SEZ6/CSMD protein family includes members that are involved in various neuronal functions. SEZ6 family proteins are implicated in cell-cell recognition, neuronal membrane signaling, and the development of dendritic arbors, contributing to the establishment of excitatory synaptic connectivity. They may also play a role in specialized endoplasmic reticulum functions within neurons. The CSMD family members are associated with dendrite development and may act as suppressors in certain types of cancer. The C4BPB proteins within this family regulate the classical pathway of complement activation, interact with anticoagulant protein S, and are involved in immune response regulation.
CoM-S-S-CoB heterodisulfide reductase (HdrB/HdrD_reductase)
Type: Family

The HdrB/HdrD family is involved in the reversible reduction of CoM-S-S-CoB to the thiol-coenzymes H-S-CoM (coenzyme M) and H-S-CoB (coenzyme B), playing a crucial role in methanogenesis. The family includes subunits of heterodisulfide reductase complexes that transfer electrons from various donors such as hydrogen, formate, or reduced ferredoxin to the disulfide bond of CoM-S-S-CoB. Some members are also capable of electron bifurcation, directing electron pairs from reduced coenzyme F420 towards the simultaneous reduction of ferredoxin and CoB-CoM heterodisulfide. This process is essential for energy conservation in methanogenic archaea and may also occur during anaerobic methane oxidation in the presence of Fe(III).
Protein Phosphatase 1 Regulatory and Actin Interaction Protein (PP1-Reg/Actin-Interact_Protein)
Type: Family

This family of proteins includes regulatory subunits that modulate the activity of protein phosphatase 1 (PP1) complexes, acting as inhibitors. They are involved in the control of various cellular processes by regulating the dephosphorylation of target proteins. Additionally, this family encompasses proteins that interact with actin cytoskeleton components, playing a role in actin polymerization and cell motility. These proteins are implicated in the formation of cell protrusions, cell polarity, and migration, as well as in signal transduction pathways related to cell activation and differentiation.
Voltage-gated chloride channel/antiporter (Cl-channel/antiporter)
Type: Family

This family of proteins includes both voltage-gated chloride channels and proton-coupled anion transporters. The channels mediate the transport of chloride ions across the membrane, which is essential for various cellular processes such as regulation of cell volume, membrane potential stabilization, and signal transduction. Some family members function as antiporters, exchanging chloride or other anions for protons, contributing to the acidification of lysosomal or endosomal lumen and playing a role in maintaining pH homeostasis. The presence of conserved gating glutamate residues is a characteristic feature of the antiporter members.
Dual-specificity lipid and protein phosphatase (Dual-spec_lipid-protein_phosph)
Type: Family

This family of proteins includes dual-specificity phosphatases with roles in dephosphorylating proteins phosphorylated on tyrosine, serine, and threonine residues. They also function as lipid phosphatases, targeting the D3 position of the inositol ring in various phosphatidylinositols, with a preference for phosphatidylinositol 3,4,5-trisphosphate. These activities are crucial for regulating signaling pathways such as the PI3K-AKT/PKB pathway, influencing cell cycle progression, cell survival, migration, and apoptosis. Some family members are involved in energy metabolism, synaptic function, and neurogenesis. They may also act as negative regulators of insulin signaling and glucose metabolism. The family's role is significant in various cellular processes, including development, chemotaxis, and cytoskeletal organization.
Arf-GAP with GTPase, ANK repeat and PH domain-containing protein (Arf-GAP_GTPase_ANK_PH)
Type: Family

This family of proteins includes GTPase-activating proteins (GAPs) for the ADP ribosylation factor family, which are involved in various cellular processes such as the regulation of the adapter protein-dependent trafficking in the endosomal-lysosomal system and the prevention of neuronal apoptosis. Some members may enhance PI3 kinase activity, mediate anti-apoptotic effects, or be involved in neurogenesis by controlling endocytosis. The GAP activity of these proteins is often regulated by phosphoinositides and can be stimulated by oxidative stress or other factors.
Secondary metabolite acyltransferase (Sec_Metabolite_Acyltrans)
Type: Family

The acyltransferase family described here is involved in the biosynthesis of various secondary metabolites, including indole alkaloids, dimeric xanthones, meroterpenoids, cyclopeptides, and ergot alkaloids . These enzymes catalyse the transfer of acyl groups, such as acetyl or other acyl-CoA derivatives, to specific substrates, leading to the modification and maturation of bioactive compounds. The family members display substrate specificity and participate in complex biosynthetic pathways, contributing to the structural diversity of natural products with pharmaceutical potential, pathogen resistance, and mycotoxin production. The enzymes are characterised by their ability to tolerate a range of acyl groups and are involved in tailoring reactions that are crucial for the biological activity and final structure of the metabolites.

This entry also includes EPS1 that harbours a non-canonical active site and an unprecedented isochorismoyl-glutamate A pyruvoyl-glutamate lyase activity that produces salicylic acid from the isochorismoyl-glutamate A substrate .
Zinc finger MYM-type/QRICH1 (ZnF_MYMT-QRICH1)
Type: Family

The Zinc finger MYM-type/QRICH1 protein family is involved in various cellular processes, including transcriptional regulation, cell morphology, cytoskeletal organization, and the integrated stress response (ISR). Members of the family function as transcriptional regulators, with some acting as mediators of the ISR by controlling protein homeostasis under ER stress conditions. They play roles in the unfolded protein response (UPR), influencing cell survival or death based on ER stress severity. Certain family members are implicated in the negative regulation of transcription, while others are associated with chondrocyte hypertrophy essential for bone growth. The CARD domain present in some members may regulate caspase activity during programmed cell death.
NADH-dependent Oxidoreductase Modular Protein (NADH_oxidoreductase_modular)
Type: Family

This family of proteins is involved in electron transfer processes, functioning as oxidoreductases. They are capable of reducing molecular oxygen to water, utilizing NADH as an electron donor. These proteins are modular, containing multiple redox cofactors, which allows them to perform activities that typically require several distinct proteins in other organisms. They may also participate in oxidative stress defense by scavenging intracellular dioxygen in anaerobic bacteria and could potentially play a role in nitric oxide detoxification. The family includes proteins with a zinc metallo-hydrolase group 3 domain at the N-terminal and a flavodoxin reductase domain at the C-terminal, indicating a bifunctional nature with both metallo-hydrolase and flavodoxin reductase activities.
Janus Kinase (JAK) (JAK)
Type: Family

The JAK family of non-receptor tyrosine kinases is pivotal in signal transduction for various cellular processes including growth, development, differentiation, and immune response. Members of the family associate with cytokine receptors, phosphorylating them upon ligand binding, which creates docking sites for STAT proteins. These STAT proteins are then phosphorylated, dimerize, and translocate to the nucleus to regulate gene transcription. The family plays roles in both innate and adaptive immunity, hematopoiesis, and cell cycle regulation. They are involved in signaling pathways for type I and type II receptors, mediating responses to growth factors, cytokines, and interferons. The JAK kinases also have regulatory domains that modulate their activity, with some acting as pseudokinases.
T cell receptor variable region (TCR_variable_region)
Type: Family

The T cell receptor (TCR) variable region family is involved in antigen recognition and is essential for the immune response. TCRs are present on the surface of T lymphocytes and recognize peptide-major histocompatibility (MH) complexes displayed by antigen presenting cells (APCs). The interaction between TCRs and pMH complexes initiates a cascade of intracellular signaling events that lead to T cell activation, growth, and differentiation. The signaling pathways include calcium, mitogen-activated protein kinase (MAPK) kinase, and nuclear factor NF-kappa-B (NF-kB) pathways. TCR diversity is generated in the thymus through V-(D)-J rearrangement and is further shaped by selection events to produce a repertoire of self-MH restricted, non-autoaggressive T cells. The family includes both alpha-beta and gamma-delta TCRs, with alpha-beta TCRs recognizing peptides and gamma-delta TCRs recognizing a variety of self and foreign non-peptide antigens.
Serum paraoxonase/arylesterase (Serum_paraoxonase/arylesterase)
Type: Family

The paraoxonase family proteins are involved in the hydrolysis of a variety of substrates, including organophosphate insecticide metabolites, lactones, and aromatic carboxylic acid esters. Members of the family exhibit a broad spectrum of enzymatic activities, such as protecting low density lipoproteins (LDL) from oxidative modification, which is implicated in atheroma formation. Some family members are associated with high density lipoprotein and exhibit antioxidant activity, potentially preventing LDL lipid peroxidation. Additionally, certain paraoxonase family proteins are involved in mechanosensory transduction, contributing to touch sensitivity by forming part of a sodium and potassium permeable channel complex. The family's diverse functions reflect its role in enzymatic detoxification, cardiovascular protection, and sensory processes.
LAGLIDADG Homing Endonuclease (LAGLIDADG_Endonuclease)
Type: Family

This family of proteins includes mitochondrial and nuclear DNA endonucleases that are primarily involved in intron homing, a process where introns or inteins are inserted into specific sites within genes. These enzymes recognize specific DNA sequences and introduce double-stranded breaks, facilitating the spread of the intron or intein that encodes them. Members of this family typically contain one or more LAGLIDADG motifs, which are characteristic of this type of homing endonuclease and contribute to their catalytic activity. Some members are also associated with complex I subunits, indicating a potential role in mitochondrial function or structure.
Ciliary Microtubule Associated (CIMAP)
Type: Family

The CIMAP family proteins are associated with the structure and function of the sperm tail, specifically the outer dense fibers. These fibers are filamentous structures located on the outside of the axoneme in the midpiece and principal piece of the mammalian sperm tail. The CIMAP family proteins are thought to play a role in maintaining the passive elastic structures and the elastic recoil of the sperm tail, which are crucial for sperm motility and fertility. The family is characterized by a similarity in sequence and structure across different species, suggesting a conserved function in sperm tail integrity and function.
Alpha-1,3-xylosyltransferase/Beta-1,3-glucuronyltransferase (Xyl/GlcA_transferase)
Type: Family

The protein family is characterized by bifunctional glycosyltransferase activities, specifically alpha-1,3-xylosyltransferase and beta-1,3-glucuronyltransferase. These enzymes are involved in the post-translational modification of alpha-dystroglycan (DAG1), a process crucial for its ability to bind laminin G-like domain-containing extracellular proteins with high affinity. The glycosylation is dependent on the phosphorylation of a core O-mannosyl trisaccharide. The family plays a significant role in the maturation of DAG1, enhancing its function in skeletal muscle and potentially in cell adhesion. Members of the family can also modify proteoglycans with glycosaminoglycan-like polysaccharides, composed of xylose and glucuronic acid, which is important for laminin binding and may impact cell adhesion and development.
Microtubule-associated tumor suppressor/Coiled-coil domain-containing protein 69 (MTUS1/CCDC69)
Type: Family

The MTUS1/CCDC69 family includes proteins that are involved in various cellular processes related to microtubule dynamics and spindle midzone assembly during mitosis. Members of the MTUS1 subfamily often cooperate with AGTR2 to inhibit ERK2 activation and cell proliferation, and may be involved in AGTR2 cell surface expression. They can also induce UBE2V2 expression upon angiotensin-II stimulation and regulate microtubule dynamics by interacting with other proteins such as MAPRE1 and KIF2C. The CCDC69 subfamily members are thought to act as scaffolds for the recruitment and assembly of spindle midzone components, and are essential for the localization of key proteins like AURKB and PLK1 to the spindle midzone. These functions suggest a role in the regulation of mitosis and cell division.
HORMA Domain-Containing Meiotic Progression (HORMA_MeioticProgression)
Type: Family

The HORMA domain-containing protein family is essential for proper meiotic progression in eukaryotes. Members of this family play multiple roles during meiosis, including the regulation of DNA double-strand break (DSB) processing, synaptonemal complex formation, and activation of the ATR kinase in response to unsynapsed chromatin. These proteins are crucial for homologous chromosome pairing and recombination, ensuring genomic stability and successful gametogenesis. They are involved in various checkpoints, particularly the male mid-pachytene and female meiotic prophase checkpoints, to monitor and maintain meiotic integrity. The family also includes proteins that coordinate the activity of recombination machinery and are implicated in meiotic silencing of unsynapsed chromatin (MSUC).
Leucine-rich glioma-inactivated/LGI-related (LGI_related)
Type: Family

This family of proteins includes regulators of voltage-gated potassium channels, influencing inactivation kinetics by interacting with specific channel subunits. They serve as ligands for certain ADAM metallopeptidase domain proteins, modulating synaptic transmission through AMPA-type glutamate receptors. Members of this family are involved in the suppression of matrix metalloproteinase production via signaling pathways. Some proteins are implicated in the development of inhibitory GABAergic synapses and the regulation of neuronal exocytosis. Additionally, they play roles in axon segregation and myelin formation within the peripheral nervous system. Overall, these proteins are key modulators of synaptic function and neural development.
Cdc42 Effector Protein BORG/CEP (Cdc42_Effector_BORG/CEP)
Type: Family

The BORG/CEP family is involved in the organization of the actin cytoskeleton and may function downstream of CDC42, a small GTPase of the Rho-subfamily, which regulates signaling pathways that control diverse cellular functions including cell morphology, migration, endocytosis, and cell cycle progression. Members of the BORG/CEP family are known to induce actin filament assembly, leading to cell shape changes and the formation of pseudopodia in fibroblasts. Some members also control septin organization, which is negatively regulated by CDC42, and can inhibit MAPK8 independently of CDC42 binding. The presence of a CRIB domain in several family members mediates their interaction with CDC42, suggesting a role in signaling pathways that orchestrate cytoskeletal dynamics and cellular morphogenesis.
PalB/RIM13 Calpain-like (PalB/RIM13)
Type: Family

This entry represents the PalB/RIM13 subfamily of the peptidase C2 family and calpain proteins found in eukaryotes.

The Calpain-like protease palB/RIM13 proteins are involved in the proteolytic cleavage of transcription factors in response to alkaline ambient pH. These proteins are crucial for the initial proteolytic cleavage within the signalling protease box of transcription factors such as pacC and pacc-1. In Aspergillus species, this cleavage results in an intermediate protein that undergoes further processing. Additionally, members of this group are implicated in virulence, particularly in invasive pulmonary aspergillosis. These proteins belong to the peptidase C2 group, specifically the PalB/RIM13 subfamily .
Heme transport and cell adhesion protein (Heme_transport/Cell_adhesion)
Type: Family

This family of proteins includes members that are involved in various biological processes, including the transport and breakdown of heme, cell adhesion, spreading, and inhibition of the membrane-damaging effect of the terminal cytolytic complement pathway. Some family members bind heme and transport it to the liver for iron recovery, while others are involved in cell-to-substrate adhesion and interact with glycosaminoglycans, proteoglycans, and certain integrins. Additionally, some proteins in this family have been identified as inhibitors of proteases and play roles in boundary lubrication within articulating joints, preventing protein deposition onto cartilage from synovial fluid.
Alpha/beta hydrolase lipase/esterase (AB_hydrolase_lip/est)
Type: Family

This entry represents a group of fungal proteins with an α/β hydrolase fold. Members of this family are involved in the hydrolysis of various ester bonds, playing roles in plant virulence, degradation of plant cell walls, and lipid metabolism. Members of the family exhibit lipase activity, targeting mono-, di-, and triacylglycerols, as well as esterase activity, hydrolysing ester bonds in arabinoxylans and pectin . Some proteins prefer specific substrates, such as p-nitrophenyl esters or acetylated compounds, and may be involved in pathogenicity by affecting plant defence mechanisms. Activity regulation is observed with inhibitors like ebelactone B or metal ions, and substrate specificity can be influenced by residues near the active site.
HMX Homeobox Transcription Factors (HMX_Homeobox_TF)
Type: Family

The HMX homeobox family comprises transcription factors involved in the development and specification of neuronal cell types, particularly within the inner ear and hypothalamus. Members of this family are known to bind specific DNA core sequences, such as 5'-CAAG-3' and 5'-CAAGTG-3', to regulate gene expression. These proteins play crucial roles in craniofacial development, including eye and ear formation, and in the CNS, where they control aspects like semicircular canal formation and hypothalamic/pituitary axis development. Some family members may function as transcriptional repressors or antagonists, influencing cell fate specification and differentiation in various tissues, including pigment cells, mesodermal lineage, and cephalic sheath glia.
Optineurin/NF-kappa-B Essential Modulator (Optineurin/NFkB_EssMod)
Type: Family

The Optineurin/NF-kappa-B essential modulator family is involved in various cellular processes including the maintenance of the Golgi complex, membrane trafficking, exocytosis, and the activation of innate immune responses. Family members interact with myosin VI and Rab8 to facilitate Golgi ribbon formation and regulate endocytic trafficking. They play a role in neuroprotection, particularly within the eye and optic nerve. Additionally, they function in the TNF-alpha signaling pathway, potentially influencing cell death induction. Members of this family serve as autophagy receptors, targeting ubiquitin-coated bacteria for degradation. They are also implicated in antiviral responses by recruiting TBK1 to phosphorylate IRF3, leading to IFN-beta production. The family's ability to bind polyubiquitin chains is crucial for the activation of NF-kappa-B, a key factor in cell survival and immune response signaling. The family's involvement in these pathways suggests a broad role in cellular homeostasis and defense mechanisms.
Dual Ser/Thr and Tyr Protein Kinase (Dual_SerThr-Tyr_Kinase)
Type: Family

The Dual serine/threonine and tyrosine protein kinase family is characterized by its role in regulating ERK phosphorylation downstream of fibroblast growth factor-receptor activation. Members of this family are involved in the regulation of both caspase-dependent apoptosis and caspase-independent cell death pathways. In particular, within the skin, these kinases are predominant in suppressing caspase-dependent apoptosis in response to UV stress across various dermal cell types. Additionally, they are implicated in embryonic development, suggesting a broader biological significance. The family's dual kinase activity reflects its capacity to phosphorylate substrates on serine/threonine as well as tyrosine residues, which is indicative of its versatile role in cell signaling and regulatory mechanisms.
Armadillo repeat-containing X-linked regulator (Armcx_regulator)
Type: Family

This family of proteins is involved in the regulation of mitochondrial dynamics, particularly affecting the distribution and transport of mitochondria within neural cells. Members of this family may interact with components of the Trak-kinesin motor complex, linking mitochondria to motor proteins and influencing their movement along axons. The proteins are implicated in processes such as axon regeneration, neuronal survival, and neurite growth. Some family members may also play a role in transcriptional regulation, influencing the expression of genes related to neuronal function. Additionally, certain proteins within this family may have a role in modulating cell survival and growth, and could interact with cellular pathways that involve tumor suppressor proteins.
SCF Complex F-box Domain-containing Protein (SCF_F-box_domain)
Type: Family

This family of proteins includes members that are typically involved in the ubiquitin-proteasome pathway. They function as components of SCF (SKP1-cullin-F-box) E3 ubiquitin ligase complexes, which play a crucial role in targeting specific proteins for ubiquitination and subsequent degradation by the proteasome. This regulatory mechanism is essential for various cellular processes, including cell cycle progression, signal transduction, and stress responses. Some family members contain an F-box domain that is critical for protein-protein interactions, particularly with SKP1 and cullin proteins, forming the core of the SCF complex. The diversity of F-box proteins allows for the recognition and ubiquitination of a wide range of substrates, thereby controlling numerous biological functions.
tRNA-specific 2-thiouridylase MnmA (tRNA_2-thiouridylase_MnmA)
Type: Family

This family of proteins is involved in the post-transcriptional modification of tRNA molecules. Specifically, they catalyze the 2-thiolation of uridine at the wobble position of tRNA, which is the 34th nucleotide from the 5' end of the tRNA sequence. The enzymatic activity results in the formation of 2-thiouridine (s(2)U34), which plays a crucial role in the proper decoding of the genetic code during protein synthesis. This modification is essential for the structural stability of tRNA and for accurate and efficient translation by the ribosome. Members of this family are found across various bacterial species and are essential for cellular function and viability.