SII-SWORD/CoKE huggingface dataset:
Heterochromatin-associated chromo domain-containing protein (Heterochromatin_chromo-domain)
Type: Family

This family of proteins is involved in the formation and maintenance of heterochromatin, a tightly packed form of DNA associated with gene repression. Members of this family recognise and bind to specific methylated lysine residues on histone H3 tails, particularly 'Lys-9', which is a hallmark of heterochromatin . Through this interaction, they contribute to the epigenetic repression of gene expression. Some proteins within this family are also implicated in the assembly of the kinetochore , a structure essential for chromosome segregation during cell division, and in the recruitment of other proteins to sites of DNA damage. Additionally, certain family members play roles in RNA interference pathways , piRNA-mediated transposon repression in the case of rhino , and the regulation of gene expression during development and the immune response .
Tail Fiber Assembly Chaperone (TFA_Chaperone)
Type: Family

This family of proteins includes chaperones that are involved in the assembly of tail fibers in bacteriophages. These proteins act catalytically to form tail protein dimers and remain associated with the tail fiber, participating in host receptor binding. The assembly of tail fibers is crucial for the bacteriophages to attach to and infect bacterial cells. Some family members are expressed alternatively, extending the host range of the virus by allowing it to bind to different receptors. The proteins are characterized by their role in the post-translational modification and assembly of bacteriophage structural components.
Low-density lipoprotein receptor-related (LDLR-related)
Type: Family

This family of proteins is involved in receptor-mediated endocytosis and internalization of various ligands, including lipoproteins, vitamins, hormones, and proteins. Members of this family play crucial roles in cellular lipid homeostasis, embryonic development, and the clearance of apoptotic cells. They are also implicated in the regulation of signaling pathways such as Wnt and BMP, and in the maintenance of the neuromuscular junction. Some members function as receptors for bacterial toxins. They are characterized by the presence of certain cytoplasmic motifs that interact with other proteins and domains essential for their sorting to specific cellular membranes.
Pentatricopeptide/CCM1 RNA-binding (PPR/CCM1_RNA-binding)
Type: Family

The PPR family proteins are characterized by their pentatricopeptide repeat motifs, which are involved in various aspects of RNA metabolism within organelles. Members of the PPR family, specifically the P subfamily, are typically localized to mitochondria or chloroplasts and play crucial roles in processes such as RNA editing, splicing, stability, and translation. They are essential for the expression and maintenance of the mitochondrial and chloroplastic genomes. The CCM1 family proteins, on the other hand, are RNA-binding proteins that facilitate the splicing of group I introns in mitochondrial transcripts and contribute to the stability of mitochondrial rRNAs, ensuring proper mitochondrial function and gene expression.
Polycystin (Polycystin)
Type: Family

The Polycystin family is involved in various functions related to calcium signaling and mechanosensation. Members of this family form heteromeric and homomeric ion channels that are permeable to cations, particularly calcium. These channels play roles in processes such as fluid-flow mechanosensation in renal epithelium, sour taste perception, and fertilization. They are also involved in the regulation of cilium length and function, which is crucial for mechanotransductive signaling and left-right axis specification during embryogenesis. Some family members act as sour taste receptors, while others are implicated in the initiation of the acrosome reaction of sperm during fertilization. The activity of these channels is regulated by factors such as phosphorylation, intracellular calcium levels, and acid stimuli.
Nickel/cobalt efflux system RcnA (NiCoT_RcnA)
Type: Family

The RcnA protein family is characterized by its role in the efflux of nickel and cobalt ions from the cell, thereby contributing to metal homeostasis and resistance to metal toxicity. Members of this family are integral membrane proteins that utilize a transport mechanism to selectively remove excess nickel and cobalt ions from the cytoplasm, preventing their accumulation to harmful levels. The RcnA family is part of the broader NiCoT transporter family, which is known for its specificity towards nickel and cobalt ions. The activity of RcnA proteins is essential for the survival of organisms in environments with varying concentrations of these metals, and it plays a crucial role in the cellular response to metal stress.
NAD(P)-dependent epimerase/dehydratase (NAD(P)_epim/dehydratase)
Type: Family

The NAD(P)-dependent epimerase/dehydratase family is characterized by enzymes that utilize NAD(+) or NADP(+) as cofactors to catalyze the epimerization or dehydration of various substrates. Members of this family are involved in diverse metabolic pathways, including the catabolism of amino acids such as L-threonine. The L-threonine 3-dehydrogenase, for instance, is an enzyme that catalyzes the NAD(+)-dependent oxidation of L-threonine to 2-amino-3-ketobutyrate. This reaction is a key step in the L-threonine degradation pathway. The family includes both characterized enzymes with known functions and uncharacterized proteins that are predicted to have similar enzymatic activities based on sequence similarity. The presence of conserved motifs and domains within this family suggests a common catalytic mechanism involving the transfer of a hydride ion to or from the NAD(+) or NADP(+) cofactor during the reaction process.
Protein Phosphatase 1 Regulatory Subunit (PP1_Regulatory_Subunit)
Type: Family

The protein family is involved in the regulation of protein phosphatase 1 (PP1) activity, which is central to various cellular processes. Members of this family mediate the binding to myosin and regulate myosin phosphatase activity, influencing muscle contraction and cell motility. Some members are involved in the dephosphorylation of key proteins such as PLK1, affecting cell cycle progression, and HIF1A, impacting cellular responses to hypoxia. Others contribute to endothelial cell barrier function, angiogenesis, and the PI3K/AKT signaling pathway. Additionally, the family includes proteins that modulate Notch and Wnt signaling pathways, playing roles in development and cell fate determination. Overall, the family members act as key regulators of various signaling cascades and cellular mechanisms through their interactions with and modulation of PP1 activity.
Chondroitin sulfate glycosyltransferase (CS_glycosyltransferase)
Type: Family

This family of proteins is involved in the biosynthesis of chondroitin sulfate, a key component of the extracellular matrix in cartilage. Members of this family exhibit glycosyltransferase activity, transferring glucuronic acid and N-acetylgalactosamine from their respective UDP-sugar donors to the growing chondroitin polymer. These enzymes play crucial roles in cartilage formation and endochondral ossification, a process where bone tissue is created. Some family members are also implicated in the metabolism of aggrecan, a major proteoglycan in cartilage, and in various developmental processes including cell division, cytokinesis, and neural development. Additionally, certain enzymes within this family are involved in the synthesis of N,N'-diacetyllactosediamine structures on glycoproteins, which are important for cell-cell interactions and signaling.
NADPH Oxidase and PX Domain-Containing (NADPH_Oxidase/PX-Domain)
Type: Family

The protein family is involved in the regulation of reactive oxygen species (ROS) generation and localization, particularly through the activation of NADPH oxidases (NOXs). Members of this family serve as organizer proteins that potentiate the superoxide-generating activity of NOX1 and NOX3, and are essential for the assembly and/or activation of the NADPH-oxidase complex, which is responsible for the oxidative burst in phagocytes. This burst is crucial for superoxide production and the immune response. Additionally, some members are required for the biogenesis of otoconia/otolith, which are important for the perception of gravity in the inner ear. Others are involved in invadopodia and podosome formation, extracellular matrix degradation, and may play a role in cell polarity, morphogenesis, and the neurotoxic effects of amyloid-beta peptide. The family is characterized by the presence of PX domains, which mediate lipid-binding and membrane localization, and SH3 domains, which facilitate interactions with other proteins.
ALYREF mRNA export adapter (ALYREF_mRNA_export)
Type: Family

The ALYREF family proteins function as export adapters involved in the nuclear export of both spliced and unspliced mRNA, playing a crucial role in mRNA processing and cytoplasmic trafficking. They are components of the TREX complex, which links transcription, splicing, and mRNA export. ALYREF family members bind to mRNA, facilitating its transfer to the NXF1-NXT1 heterodimer for export via the TAP/NFX1 pathway. They are involved in transcriptional activation by acting as chaperones that promote the dimerization of transcription factors with bZIP domains. Additionally, they contribute to genome stability and transcription elongation. Some family members are implicated in the export of m5C-containing mRNAs and in defense responses in plants. The TREX complex, including ALYREF proteins, is essential for the export of certain viral mRNAs and may be recruited to mRNA independently of transcription.
Amyloid-beta A4 Precursor Protein-Binding (APP-Binding)
Type: Family

The Amyloid-beta A4 precursor protein-binding family is involved in synaptic vesicle exocytosis and modulation of amyloid-beta precursor protein (APP) processing, potentially affecting APP-beta formation. Members of the family interact with essential components of the synaptic vesicle exocytotic machinery, such as STXBP1 and Munc18-1. They contain a phosphotyrosine-binding domain (PID/PTB) for binding the cytoplasmic domain of APP and PDZ domains for membrane attachment. Some members also participate in vesicular trafficking and may influence the activity of transcription factors and receptors, contributing to processes like cell migration, proliferation, and cell cycle progression in various cell types. The family includes proteins that may enhance HIF1A activity in macrophages and are involved in exosome biogenesis and tumorigenesis.
SOSS complex subunit B (SOSS-B)
Type: Family

The SOSS-B family is involved in the cellular DNA damage response, particularly in promoting DNA repair and the G2/M checkpoint. Members of the family function as components of the SOSS complex, which operates downstream of the MRN complex. They act as sensors of single-stranded DNA, with a preference for polypyrimidines, and are essential for homologous recombination-dependent repair of double-strand breaks and ATM-dependent signaling pathways. The SOSS complex's association with DNA lesions is crucial for cell-cycle checkpoint activation, recombinational repair, and maintaining genomic stability.
AT-rich Interactive Domain/SWI1 Chromatin Remodeling (ARID/SWI1_ChromRemod)
Type: Family

The ARID/SWI1 protein family includes transcriptional regulators with diverse roles in gene expression, chromatin remodeling, and developmental processes. Members of the family bind to AT-rich DNA regions and can act as transcription coactivators or repressors. They are involved in adipogenesis, liver development, spermatogenesis, myeloid homeostasis, and may also regulate smooth muscle cell differentiation and proliferation. Some family members form complexes with other proteins, such as the mSin3A corepressor complex, to modulate transcription factor activity and histone modifications. They also play roles in epigenetic regulation at imprinting centers and in the stabilization of inflammation-related mRNAs. The SWI/SNF subunits within the family are part of an ATP-dependent chromatin remodeling complex that alters nucleosome position to regulate gene expression.
Desulfoferrodoxin superoxide reductase (Desulfoferrodoxin_SOR)
Type: Family

The desulfoferrodoxin family comprises proteins that play a crucial role in the detoxification of reactive oxygen species, particularly the superoxide anion radical. Members of this family are characterized by their ability to catalyze the one-electron reduction of superoxide to hydrogen peroxide. This activity is essential for protecting cells from oxidative stress. The proteins are typically organized into two domains, with each domain containing a distinct mononuclear iron center. The N-terminal domain resembles desulforedoxin and includes a Fe(3+) ion, while the second domain harbors a Fe(2+) ion. Some family members utilize electrons from reduced NADP, transferred via rubredoxin and an oxidoreductase, to perform the reduction. This family is significant in various organisms, including obligate anaerobic bacteria, where it forms part of a pathway for reactive oxygen species detoxification.
TAO Serine/Threonine-Protein Kinase (TAO_STE20_kinase)
Type: Family

The TAO kinase family is involved in various cellular processes, including the regulation of the p38/MAPK14 and MAPK8/JNK stress-activated MAPK cascades, DNA damage response, and cytoskeleton stability. Members of the family function as serine/threonine-protein kinases that activate MAPK cascades by phosphorylating upstream kinases such as MAP2K3 and MAP2K6. They are implicated in the G2/M transition DNA damage checkpoint and regulate cytoskeleton stability by phosphorylating proteins like MARK2, affecting microtubule dynamics. Additionally, they play roles in apoptosis, neuronal development and migration, and cell cycle progression. Some members also participate in G-protein coupled receptor signaling, osmotic stress response, and meiotic recombination. The family includes isoforms with distinct functions, such as regulation of endocytosis and organ size control via the Hippo/SWH signaling pathway.
Centrosomal Protein 152/SHC-Transforming Protein (CEP152/SHC-Transforming)
Type: Family

The CEP152 family is involved in centrosome duplication and centriole formation. Members act as molecular scaffolds, facilitating interactions between key molecules such as PLK4 and CENPJ. They are essential for recruiting CDK2, which is required for centriole duplication. The family also plays a significant role in deuterosome-mediated centriole amplification in multiciliated cells, enabling the generation of over 100 centrioles. Overexpression of CEP152 family members can induce centriole amplification. In contrast, the SHC family members function as signaling adapters, coupling activated growth factor receptors to various signaling pathways. They are involved in pathways initiated by receptors like KIT and TEK/TIE2, influencing processes such as endothelial cell migration, sprouting angiogenesis, and neuron signaling. Specific members also activate Ras-dependent and independent pathways and contribute to stress response signaling.
Histone acetyltransferase RTT109-like (HAT_RTT109-like)
Type: Family

This family of proteins includes histone acetyltransferases, such as RTT109, which are known to acetylate lysine residues on histone H3. This modification plays a crucial role in nucleosome assembly, genomic stability, DNA repair, and transcriptional regulation during the S-phase of the cell cycle. The acetylation of specific lysine residues, such as 'Lys-56', weakens the interaction between the histone core and DNA, facilitating chromatin disassembly. Some family members are also capable of autoacetylation and may interact with histone chaperones to influence their substrate specificity.
Ferric-chelate Reductase and Defense (Ferric-chelate_Red/DefProt)
Type: Family

The protein family includes ferric-chelate reductases and putative defense proteins. Ferric-chelate reductases are involved in the reduction of Fe(3+) to Fe(2+), facilitating iron transport from the endosome to the cytoplasm. Members of the family that are putative defense proteins are suggested to have antimicrobial activity, possibly expressed in response to bacterial infection. The family encompasses proteins with a shared similarity, indicating a conserved function or structural domain across the family members.
GDSL esterase/lipase (GDSL_esterase/lipase)
Type: Family

This family of proteins includes enzymes with esterase and lipase activities, characterized by the presence of a GDSL motif. These enzymes are involved in a variety of biological processes, including lipid metabolism and plant defense mechanisms. One member is specifically implicated in systemic acquired resistance and may participate in long-distance signaling within the plant. The GDSL motif is a conserved sequence that is integral to the catalytic function of these enzymes, which hydrolyze ester bonds in lipids.
2'-Deoxynucleoside 5'-phosphate N-hydrolase (2'-dNMP_N-hydrolase)
Type: Family

This family of proteins is involved in a nucleotide salvage pathway that processes epigenetically modified nucleotides to prevent their incorporation into DNA. Specifically, these enzymes catalyze the hydrolysis of the N-glycosidic bond in 5-hydroxymethyl-dUMP (hmdUMP), a cytotoxic nucleotide, converting it into non-toxic components. This reaction results in the formation of 5-hydroxymethyluracil and 2-deoxy-D-ribose 5-phosphate. By degrading hmdUMP, these proteins play a crucial role in maintaining genomic stability and preventing the integration of potentially harmful nucleotides into the genome.
Mitochondrial RNA Processing and Respiration (Mito_RNA-Proc/Resp)
Type: Family

The protein family is involved in various mitochondrial functions, including the maintenance of mitochondrial genome expression, RNA processing, and respiration. Members of the family are RNA-binding proteins that participate in the specific removal of group I introns from mitochondrial encoded transcripts, which is crucial for the stability of the mitochondrial 15S rRNA. Additionally, some family members are involved in the editing of mitochondrial mRNAs and may play a role in restoring male fertility in plants by blocking the production of cytotoxic peptides. The family also includes proteins required for respiration, highlighting their essential role in cellular energy metabolism.
DZIP and RILPL (DZIP_RILPL)
Type: Family

The DZIP/RILPL protein family is involved in the assembly and function of cilia, as well as in cellular transport and cell shape and polarity regulation. Members of the family, such as DZIP1 and DZIP1L, act as molecular adapters recruiting protein complexes to the cilium basal body, facilitating vesicle-mediated transport of proteins, and playing roles in Hedgehog signaling and spermatogenesis. They are also involved in the organization of the basal body and assembly of the sperm flagellum. RILPL proteins, on the other hand, are involved in the regulation of cell shape and polarity, cellular protein transport, and neuroprotection by sequestering GAPDH in the cytosol. They also interact with RAB10, influencing ciliogenesis. Overall, the family contributes to the structural and functional integrity of cilia, cellular organization, and signaling pathways.
WD repeat and EF-hand domain-containing protein (WD-EF-hand_domain)
Type: Family

This family of proteins contains WD repeat motifs, which are minimally conserved regions of approximately 40 amino acids typically bracketed by glycine-histidine (GH) and tryptophan-aspartic acid (WD) dipeptides. These repeats are involved in the formation of beta-propeller structures that facilitate protein-protein interactions. Members of this family are implicated in a variety of cellular processes, including signal transduction, RNA processing, gene regulation, vesicular trafficking, cytoskeletal assembly, and cell cycle control. Additionally, some members possess EF-hand calcium-binding domains, suggesting a role in calcium-mediated signaling pathways.
Polycomb group WD repeat-containing protein (PcG_WD-repeat)
Type: Family

This family of proteins is involved in epigenetic regulation of gene expression through the modification of histones. Members of this family are part of the Polycomb group (PcG) proteins, which form multiprotein complexes that methylate specific lysine residues on histone H3, leading to transcriptional repression of target genes. These modifications can heritably alter chromatin structure and maintain the repressed state of genes across cell divisions. Functions of these proteins include roles in development, such as the maintenance of homeotic gene repression, regulation of seed endosperm development, and X chromosome inactivation. They are also implicated in the regulation of various metabolic processes and cellular differentiation. The WD repeat domain within these proteins is responsible for recognizing specific trimethylated histone peptides, contributing to the targeting of the PcG complexes to chromatin.
TRPM8 Channel-Associated Factors (TCAF)
Type: Family

The TCAF family is involved in the regulation of the TRPM8 cation channel, with members either positively or negatively affecting the channel's activity. Positive regulators enhance TRPM8 activity, facilitate its recruitment to the cell surface, and inhibit prostate cancer cell migration in a TRPM8-dependent manner. Negative regulators, conversely, decrease TRPM8 activity and promote prostate cancer cell migration stimulation, also in a TRPM8-dependent fashion. The C-terminal region of these proteins is crucial for their role in channel activity stimulation. Additionally, some members of the family may play a role in the type II secretion system for the export of folded proteins across the outer membrane.
eIF5-mimic translation initiation regulator (eIF5-mimic_regulator)
Type: Family

The elf5-mimic protein family functions as translation initiation regulators. They are known to repress non-AUG-initiated translation and repeat-associated non-AUG (RAN)-initiated translation, acting as competitive inhibitors of eukaryotic translation initiation factor 5 (EIF5). These proteins increase the accuracy of translation initiation by competing with EIF5 for interaction with EIF2S2 within the 43S pre-initiation complex, in a manner dependent on binding to EIF3C. Additionally, some members of this family are involved in enhancing histone H4 gene transcription, although they do not directly bind to DNA .
WD repeat-containing protein 48 (WDR48)
Type: Family

The WDR48 family proteins are regulators of deubiquitinating complexes, enhancing the activity of USP1, USP12, and USP46 by increasing catalytic turnover without affecting substrate affinity. They play a crucial role in DNA repair processes, particularly by stimulating RAD51-mediated homologous recombination and participating in PCNA-mediated translesion synthesis. These proteins are also involved in the recruitment of RAD51 to replication forks under stress and bind both single-stranded and double-stranded DNA. In addition, they are implicated in cellular responses to viral infections, potentially affecting vesicular transport and membrane fusion events, as well as maintaining viral genomes. Some family members interact with ubiquitin and are involved in resistance to various compounds.