SII-SWORD/CoKE huggingface dataset:
Notch signaling pathway (Notch_signaling)
Type: Family

The Notch signaling pathway family is involved in a wide range of developmental processes and cell fate determinations. Members of this family function as receptors for membrane-bound ligands, such as Jagged and Delta proteins, to regulate differentiation, proliferation, and apoptosis. Activation of Notch receptors leads to the release of the Notch intracellular domain, which forms a transcriptional activator complex and initiates gene expression. This family plays a crucial role in neurogenesis, angiogenesis, somitogenesis, and the development of various tissues including the vascular system, immune system, and muscles. It is also implicated in maintaining stem cell populations and in lateral inhibition, a process ensuring that neighboring cells do not adopt the same differentiation pathway.
Serine/Arginine-Rich Splicing Factor (SRSF)
Type: Family

The Serine/Arginine-Rich Splicing Factor (SRSF) family is involved in various aspects of mRNA processing, particularly in pre-mRNA splicing. Members of this family play roles in constitutive and alternative splicing, influencing exon inclusion or skipping. They are also implicated in spliceosome assembly and intron recognition. Some SRSFs have functions in miRNA processing and pri-miRNA biogenesis. Additionally, certain SRSFs act as export adapters in mRNA nuclear export, interacting with NXF1-NXT1 and recognizing m6A-modified RNAs. Their RNA-binding activity is semi-sequence specific, and they may have developmental roles or contribute to the regulation of neuron-specific alternative splicing. The SRSF family is characterized by the presence of one or more RNA recognition motifs (RRMs) and an arginine/serine-rich domain, which is essential for their splicing regulatory functions.
DNA gyrase inhibitor (DNA_gyrase_inhibitor)
Type: Family

The DNA gyrase inhibitor family comprises proteins that protect cells against toxins targeting DNA gyrase by inhibiting the supercoiling activity of the enzyme. These inhibitors act at an early step, either prior to or at the step of DNA binding by gyrase. By inhibiting the activity of toxins and reducing the formation of lethal double-strand breaks in the cell, members of the family play a crucial role in cellular defense mechanisms against DNA damage. Some family members are also implicated in transcriptional regulation, such as repressing the expression of specific genes, and may have a broader role in protecting cells against various forms of DNA damage.
Bacterial Autotransporter Virulence Factors (Bact_Autotransporter_VF)
Type: Family

The protein family includes autotransporter proteins primarily involved in virulence and host interaction. Autotransporters are characterized by their ability to facilitate their own translocation across the bacterial outer membrane. The family members possess a signal peptide that guides them to the periplasmic space, followed by a C-terminal translocator domain forming a pore in the outer membrane for passenger domain translocation to the cell surface. Functions vary but include serine protease activity, mucinolytic activity, hemagglutination, heme binding, and immunoglobulin A1 cleavage. Some members act as adhesins, mediating bacterial attachment and invasion, or contribute to biofilm formation and autoaggregation. The family plays a significant role in bacterial pathogenicity by facilitating colonization, evasion of host immune responses, and nutrient acquisition.
JMJD6 family arginine demethylases/lysyl-hydroxylases (JMJD6_ArgDemeth/LysHydrox)
Type: Family

The JMJD6 family proteins are multifunctional dioxygenases with roles in RNA splicing, gene expression regulation, and embryonic development. They exhibit bifunctional activity, acting as both arginine demethylases and lysyl-hydroxylases. Members of this family are involved in the hydroxylation of specific lysine residues on target proteins, which is crucial for processes such as RNA splicing and nucleolar organization. Additionally, they demethylate arginine residues on histones and other proteins, influencing the histone code and transcriptional regulation. These proteins are implicated in hematopoietic differentiation, angiogenic sprouting, and macrophage cytokine responses. Some family members also interact with transcriptional machinery to modulate polymerase II promoter-proximal pause release and transcriptional activation. The nuclear localization signal motifs within these proteins are key for their nuclear targeting.
DRAM/TMEM150 Autophagy Modulator (DRAM/TMEM150_Autophagy_Mod)
Type: Family

The DRAM/TMEM150 family includes proteins that play diverse roles in cellular processes. Members of this family are involved in the modulation of macroautophagy, contributing to the accumulation of autophagosomes and enhancing autophagic flux, which can affect cell survival under stress conditions such as nutrient deprivation. Some proteins within the family act as lysosomal modulators of autophagy and are implicated in p53/TP53-mediated apoptosis. Others are components of mechanosensitive cation channels, potentially contributing to proprioception. Additionally, certain members regulate the localization of phosphatidylinositol 4-kinase to the plasma membrane, influencing phosphatidylinositol 4-phosphate synthesis. The family also includes proteins that may play roles in extracellular matrix engulfment, growth factor receptor recycling, and photoreceptor cell renewal in the retina.
Lysyl oxidase-like protein (LOX-like_protein)
Type: Family

This family of proteins is involved in the post-translational modification of extracellular matrix components, particularly in the oxidative deamination of lysine residues in collagen and elastin precursors, which is essential for the formation of cross-links that stabilize these structures. Members of this family also function as transcription corepressors, regulating gene expression by modifying histone lysine residues and other transcription factors. They are implicated in various biological processes including tissue remodeling, inflammatory response regulation, cell differentiation, and embryonic development. Some members have been associated with the epithelial to mesenchymal transition, influencing cell adhesion and migration, and may play roles in angiogenesis and tumor suppression.
AP2/ERF Ethylene-responsive transcription factor (AP2/ERF_ERF_subfamily)
Type: Family

The AP2/ERF transcription factor family, specifically the ERF subfamily, is involved in a wide range of plant developmental processes and stress responses. Members of this family typically function as transcriptional activators, binding to the GCC-box pathogenesis-related promoter element to regulate gene expression. They play key roles in the cytokinin signaling pathway, affecting the development of cotyledons, leaves, and embryos. Some members are also implicated in cuticle formation by inducing wax biosynthesis, conferring drought resistance. Additionally, certain proteins within this family are involved in symbiotic nodule signaling, root infection by symbiotic rhizobia, and nodule development in response to rhizobial Nod factors.
Small nuclear ribonucleoprotein-associated SmB/NAA38-like (snRNP_SmB/NAA38-like)
Type: Family

The snRNP SmB is involved in the fundamental process of pre-mRNA splicing, serving as core components of the spliceosomal U1, U2, U4, and U5 small nuclear ribonucleoproteins (snRNPs). These snRNPs are essential building blocks of the spliceosome, the complex responsible for the removal of introns from pre-mRNA . Members of the family participate in the formation of both the pre-catalytic spliceosome B complex and the activated spliceosome C complexes. They also play roles in the splicing of U12-type introns and in histone pre-mRNA 3'-end processing as part of the U7 snRNP. Some members may be involved in tissue-specific alternative RNA processing events. This entry also includes N-alpha-acetyltransferase 38, NatC auxiliary subunit (NAA38) which functions as an auxiliary component of the N-terminal acetyltransferase C (NatC) complex, which catalyses the acetylation of N-terminal methionine residues on nascent polypeptides .
MAP kinase kinase (MAP_kinase_kinase)
Type: Family

The MAP kinase kinase family comprises dual specificity protein kinases that play a central role in the MAP kinase signal transduction pathway. These kinases are activated by a variety of extracellular signals including growth factors, cytokines, and hormones. Upon activation, they phosphorylate and activate MAP kinases, particularly ERK1 and ERK2, through the phosphorylation of threonine and tyrosine residues within a Thr-Glu-Tyr motif. The MAP kinase cascade mediates cellular responses such as growth, adhesion, survival, and differentiation, influencing transcription, metabolism, and cytoskeletal arrangements. The family also includes kinases involved in cell wall integrity, oxidative stress response, and pathogenic processes such as appressorium formation and invasive growth. Regulatory mechanisms include phosphorylation by upstream kinases, binding to scaffold proteins like KSR1 or KSR2, and negative feedback through phosphorylation by substrate kinases.
SCAN domain and C2H2-type zinc finger (SCAN-C2H2_zinc_finger)
Type: Family

The protein family is characterized by the presence of a SCAN domain and often includes C2H2-type zinc finger domains, indicating a role in DNA binding and transcriptional regulation. Members of the family are involved in various regulatory functions, such as transcriptional repression and activation, and are essential for processes like myelination in oligodendrocytes and maintenance of progenitor cells in the CNS. They can bind specific DNA sequences and may act as transcription factors, influencing the transition from premyelinating to myelinating states in oligodendrocytes and promoting cell cycle progression in CNS development.
SOX Transcription Factors (SOX_TF)
Type: Family

The SOX family of transcription factors is characterized by the presence of a high-mobility group (HMG) DNA-binding domain and plays a pivotal role in the regulation of embryonic development and in the determination of cell fate. Members of the family are involved in a variety of biological processes, including neural crest formation, chondrogenesis, and the development of the central nervous system and glia. They are known to bind specific DNA motifs to activate gene expression related to myelination, cartilage formation, and the development of various cell lineages, such as chondrocytes and neural crest-derived cells. The family's activity is modulated by transactivation domains, such as TAM, TAC, and the 9aaTAD motif, which interact with transcriptional coactivators and the basal transcriptional machinery to induce gene transactivation.
CNF-like Phospholipase A2 Inhibitor (CNF-like_PLA2_Inhibitor)
Type: Family

The CNF-like-inhibitor family comprises proteins that function primarily as inhibitors of phospholipase A2 (PLA2), an enzyme involved in the release of arachidonic acid from phospholipids and subsequent production of eicosanoids. Members of the family bind to PLA2 with varying affinities, neutralizing the enzyme's activity and preventing the formation of inflammatory mediators. Some family members exhibit broad-spectrum neutralization of snake venom toxicity and display anti-hemorrhagic activities. Additionally, certain proteins within this family, such as Ly6/PLAUR domain-containing proteins, play a role in maintaining intestinal homeostasis by preventing bacterial invasion and motility within the colon epithelium. The family's involvement extends to modulating immune responses and contributing to bone growth or remodeling.
NKG2/CD94 Natural Killer Receptors (NKG2/CD94_NK_receptors)
Type: Family

The NKG2/CD94 receptor family includes activating and inhibitory receptors expressed on natural killer (NK) cells and some T-cell subsets. These receptors play crucial roles in immune surveillance by recognizing MHC class I molecules, particularly HLA-E in humans, which present self or virally derived peptides. The family members regulate NK cell activation, effector functions, and contribute to the immune response against viral infections and tumor cells. They are involved in maternal-fetal tolerance and may be implicated in autoimmunity prevention. Some family members can induce cell exhaustion in the tumor microenvironment, acting as immune checkpoints. Viral evasion strategies include the manipulation of these receptors to avoid immune detection. The receptors typically signal through associations with adapter proteins like TYROBP/DAP12, leading to cell activation or inhibition via phosphorylation or dephosphorylation of signaling molecules.
Nematode receptor-like class delta (Nematode_rcpt-like_delta)
Type: Family

This family of proteins includes members that are thought to function as chemosensory receptors. These receptors are likely involved in the detection of environmental cues and play a role in sensory perception. The proteins share a common structural framework that suggests a role in signal transduction processes, which are critical for the organism's interaction with its environment. Given the similarity annotations, these proteins may share conserved features that are characteristic of the nematode receptor-like protein class, indicating a specialized function in nematode species.
Type IV secretion system, general secretion pathway E ATPase (T4SS_GSP_E_ATPase)
Type: Family

The general secretion pathway (GSP) E family proteins are involved in various types of bacterial secretion systems and pilus functions. They act as ATPases, providing energy through ATP hydrolysis for processes such as protein export, DNA transfer to plants, and pilus retraction. These proteins are key components of type IV secretion systems, which are major virulence determinants in pathogenic bacteria, affecting host cell functions and contributing to bacterial survival, colonization, and pathogenesis. They also play roles in biofilm maturation and twitching motility, which are forms of surface-associated movements facilitated by type IV pili. The family includes proteins like VirB11, which are essential for pathogenesis and intracellular survival, and PilT, which is involved in pilus retraction and host cell adhesion.

This entry also includes archaeal ATPases such as Archaeal flagellar ATPase motor FlaI from Sulfolobus acidocaldarius, a component of the archaellum that provides the energy for both archaellum assembly and rotation .
LytR/CpsA/Psr cell wall biosynthesis (LytR/CpsA/Psr_CW_biosynth)
Type: Family

The LytR/CpsA/Psr (LCP) family proteins are involved in cell wall biosynthesis and maintenance. Members of this family are responsible for the transfer of anionic cell wall polymers (APs) from their lipid-linked precursors to peptidoglycan, which is a critical step in cell wall teichoic acid biosynthesis. This function is essential for maintaining cell wall integrity and is implicated in the regulation of resistance to certain antibiotics, such as oxacillin and teicoplanin. Additionally, some family members are associated with the regulation of virulence factors, biofilm formation, and stress response mechanisms. The LCP family includes proteins with regulatory roles, such as MsrR, which is involved in SarA attenuation, affecting both antibiotic resistance and virulence factor synthesis. Other members, like TagU, TagT, and TagV, are polyisoprenyl-teichoic acid--peptidoglycan teichoic acid transferases, directly participating in teichoic acid attachment to the cell wall. The family also encompasses proteins with broader roles in cell wall biosynthesis, such as LcpA, which may transfer arabinogalactan onto peptidoglycan.
Cellular Process Regulator and RNA Processing Protein (Cell_Proc_Reg/RNA_Proc)
Type: Family

This family of proteins includes regulators of various cellular processes such as metabolism, cell growth, and RNA processing. Members of this family are involved in the regulation of glutamate metabolism and the inhibition of 2-oxoglutarate dehydrogenase, a key enzyme in the Krebs cycle, through phosphorylation-dependent mechanisms. Some proteins in this family function as inhibitors of protein phosphatase 1, thereby influencing cell proliferation and pre-mRNA splicing. Others are implicated in the biogenesis of microRNAs and the stability of specific mRNAs. Additionally, certain members are associated with the spliceosome and are required for the splicing of pre-mRNAs. The family also includes proteins that may act as transcriptional repressors and participate in signaling pathways.
Thiol-specific peroxidase BCP/PrxQ (Peroxiredoxin_BCP/PrxQ)
Type: Family

This family of proteins functions as thiol-specific peroxidases, catalyzing the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. They play a crucial role in cellular protection against oxidative stress by detoxifying peroxides. Additionally, they act as sensors of hydrogen peroxide-mediated signaling events. Some members are involved in various cellular processes, including telomere silencing, telomere length regulation, and post-diauxic growth. In plants, they are involved in defense against pathogens and protection of the photosystem II against oxidative damage.
Rhomboid protease S54 (Rhomboid_protease_S54)
Type: Family

The Rhomboid protease S54 family comprises mitochondrial and chloroplastic serine proteases involved in intramembrane proteolysis. Members of this family play crucial roles in various cellular processes, including the regulation of mitochondrial function, apoptosis, cell division, and sporulation. They are responsible for the proteolytic processing of several key proteins such as OPA1, PINK1, PGAM5, DIABLO/SMAC, and others, which are essential for maintaining mitochondrial integrity, morphology, and the apoptotic response. Some family members are also implicated in plant-specific functions such as root growth, floral development, and photoprotection. The family is characterized by its ability to cleave substrates within the membrane, a feature that distinguishes it from many other proteases.
Aconitase/IPM Isomerase (Aconitase/IPM_isomerase)
Type: Family

The Aconitase/IPM Isomerase family is involved in several metabolic pathways, including the tricarboxylic acid (TCA) cycle and the alpha-aminoadipate pathway for lysine biosynthesis. Family members catalyze the isomerization of citrate to isocitrate via cis-aconitate, a key step in the TCA cycle. Some members also catalyze the reversible dehydration of (R)-homocitrate to cis-homoaconitate, which is part of lysine biosynthesis. Additionally, certain proteins within the family are implicated in the catabolism of short chain fatty acids through the TCA and 2-methylcitrate cycles. The family includes proteins with RNA-binding regulatory functions, influencing the synthesis of other proteins and contributing to post-transcriptional regulation. Some members are essential for mitochondrial DNA maintenance, protecting against mutations and breaks. The family is characterized by a diverse range of functions, including metabolic enzyme activity, regulatory roles, and contributions to genetic stability.
Transient receptor potential cation channel M (TRPM)
Type: Family

The TRPM family comprises ion channels with diverse regulatory mechanisms and functions, including cellular divalent cation homeostasis, sensory perception, and response to environmental changes. Members are involved in mediating calcium and magnesium influx, contributing to membrane depolarization, and are activated by various stimuli such as temperature changes, ligand binding, and intracellular Ca(2+) levels. Some members possess kinase activity, playing roles in phosphorylation processes. The family is implicated in physiological processes like taste transduction, insulin secretion, cell migration, and response to oxidative stress. TRPM channels are also essential in neuronal cell death regulation and immune responses.
ATP-dependent Zinc Metalloprotease (ATP-dep_Zn_Metalloprotease)
Type: Family

The ATP-dependent zinc metalloprotease family, characterized by the presence of peptidase M41 and AAA ATPase domains, is involved in the quality control, assembly, and regulation of mitochondrial and membrane proteins. Members of this family exhibit processive, ATP-dependent metallopeptidase activity, targeting both cytoplasmic and membrane proteins for degradation. They play crucial roles in the maintenance of mitochondrial function, including the formation and regulation of the mitochondrial permeability transition pore, the turnover of misfolded or mistranslated polypeptides, and the assembly of mitochondrial respiratory chain complexes. Some family members are essential for neuron development, mediating the degradation of specific mitochondrial proteins to promote efficient assembly of protein complexes. This family also contributes to the proteolytic maturation of other mitochondrial proteases and is involved in the regulation of mitochondrial dynamics through the processing of key proteins like OPA1.
Phosphofructokinase type A (PFKA)
Type: Family

This family of proteins includes enzymes that catalyze the phosphorylation of D-fructose 6-phosphate. Members of this family are involved in the first committing step of glycolysis, using either ATP or inorganic phosphate (PPi) as a phosphoryl donor. The ATP-dependent enzymes convert D-fructose 6-phosphate to fructose 1,6-bisphosphate, a key regulatory step in glycolysis. In contrast, the PPi-dependent enzymes can function in both glycolysis and gluconeogenesis due to the reversible nature of the reaction they catalyze. This reversible reaction allows these enzymes to replace both the forward ATP-dependent phosphofructokinases and the reverse fructose-bisphosphatase enzymes. Some family members are regulated allosterically, while others are non-allosteric, indicating a diversity in regulatory mechanisms within the family.
Major Facilitator Superfamily Vesicular Transporter (MFS_Vesicular_Transporter)
Type: Family

The Major Facilitator Superfamily (MFS) Vesicular Transporter family is involved in the electrogenic antiport of various substrates across cellular membranes. Members of this family exchange cationic neurotransmitters or polyamines with protons, utilizing the electrochemical proton gradient generated by V-type proton-pump ATPases. This process is essential for the accumulation of neurotransmitters such as acetylcholine, dopamine, adrenaline, noradrenaline, histamine, serotonin, and polyamines like spermine and spermidine inside secretory vesicles. These vesicles release their contents via exocytosis, playing a critical role in neurotransmission, memory formation, and response to environmental stimuli. Some family members are also implicated in the transport of secondary metabolites with insecticidal activity and alpha-ketoglutarate permeation.
Mitochondrial Protein Transport Metaxin (Mito_Protein_Transport_Metaxin)
Type: Family

This family of proteins is primarily involved in the transport of proteins into the mitochondrion, a critical process for mitochondrial function and biogenesis. Members of this family are essential for embryonic development, indicating a vital role in early stages of life. Some proteins within this family may also have a role in axonal development, suggesting a broader functional spectrum beyond mitochondrial import.
TM2 domain-containing protein 1-3-like (TM2D1-3-like)
Type: Family

This entry represents a group of proteins that contain

, including human TM2 domain-containing protein 1-3 (TM2D1-3). TM2D1, also known as Amyloid-beta-binding protein, may participate in amyloid-beta-induced apoptosis through interactions with beta-APP42 . Drosophila member Almondex is involved in the control of cell fates in the neurectoderm and act as positive regulators of the Notch signalling pathway .