SII-SWORD/CoKE huggingface dataset:
eIF2B Complex Subunit Epsilon (eIF2B_epsilon)
Type: Family

This family of proteins functions as components of the translation initiation factor 2B (eIF2B) complex. They possess guanine nucleotide exchange factor activity, catalyzing the exchange of GDP for GTP on the eIF2 gamma subunit. This activity is crucial for the initiation of protein synthesis by facilitating the binding of methionyl-initiator methionine tRNA to the ribosome. The activity of these proteins is regulated by the phosphorylation state of the eIF2 alpha subunit; when eIF2 is phosphorylated, the exchange factor activity is repressed, leading to a reduction in global protein translation. Additionally, some members of this family are known to be activated by specific chemicals that can modulate their activity under stress conditions.
Cysteine-rich secretory LCCL domain-containing protein (CRISP-LCCL_domain)
Type: Family

This family of proteins includes members that are known to promote matrix assembly. They are characterized by the presence of a cysteine-rich secretory LCCL domain. The LCCL domain is implicated in various biological processes, including cell adhesion, migration, and the organization of extracellular components. Members of this family share a similarity with the CRISP family, suggesting a potential role in immune defense, fertility, or pathogen interaction, as CRISP proteins are known to function in these areas. However, the full range of functions and physiological roles for this protein family remains to be fully elucidated.
Alba-like nucleic acid-binding (Alba-like_NAB)
Type: Family

This family of proteins includes members that are involved in nucleic acid binding and processing. Some members have been characterized to bind DNA and RNA with relaxed sequence specificity, and are associated with subtelomeric repeats. Others are known to be components of ribonucleoprotein complexes such as ribonuclease P and MRP ribonuclease complex, which are involved in the generation of mature tRNA molecules by cleaving their 5'-ends and in the cleavage of pre-rRNA sequences, respectively. The functions of these proteins suggest a role in the regulation of gene expression at both transcriptional and post-transcriptional levels.
PAK1 Kinase Regulator (PAK1-Kinase_Regulator)
Type: Family

This family of proteins is involved in the negative regulation of PAK1 kinase, a key player in various signaling pathways, including those that involve MAPK8 and RELA. PAK1, which is part of the PAK kinase family, is typically found as an inactive homodimer that becomes activated upon binding with small GTPases such as CDC42 at its N-terminal regulatory domain. Members of this protein family can bind to the N-terminus of PAK1, thereby inhibiting its activation by CDC42. Additionally, these proteins may have a role in the assembly of the ribosomal large subunit, which is crucial for protein synthesis. One member is also implicated in the assembly of 60S pre-ribosomal particles and may influence the translation of viral mRNAs. Another member is associated with cytoskeletal remodeling and cytokinetic functions through its interaction with and regulation of pak1/shk1 kinase activity.
Eukaryotic Initiation Factor 2B Subunit Gamma (eIF2B_gamma)
Type: Family

This family of proteins functions as components of the eukaryotic translation initiation factor 2B (eIF2B) complex. They play a crucial role in the initiation of protein synthesis by catalyzing the exchange of GDP for GTP on the eIF2 complex gamma subunit. This exchange is essential for the recruitment of methionyl-initiator methionine tRNA to the ribosome. The activity of these proteins is regulated by the phosphorylation status of the eIF2 alpha subunit, with phosphorylation repressing their guanine nucleotide exchange factor activity, leading to a reduction in global protein synthesis. Additionally, some members are known to be activated by specific chemical inhibitors of the integrated stress response, which enhance their activity regardless of the phosphorylation state of eIF2.
Fungal Secondary Metabolite Dioxygenase (Fungal_Metabolite_Diox)
Type: Family

This family of proteins includes dioxygenases involved in the biosynthesis of various fungal secondary metabolites, such as ergot alkaloids, swainsonine, communesins, fumitremorgins, and kanamycin. These enzymes catalyze oxidative reactions that are essential for the formation of bioactive compounds with potential pharmaceutical applications. The reactions mediated by these proteins are often part of complex biosynthetic pathways that transform simple precursor molecules into structurally diverse and biologically active alkaloids. The family members share a common function in introducing oxygen into substrates, which can lead to the formation of new bonds, ring structures, or the activation of molecules for further modification.
Cuticlin domain-containing protein (Cuticlin)
Type: Family

This family of proteins is involved in the formation and structural integrity of cuticles, which serve as protective envelopes for organisms. Members of this family play crucial roles in the development of alae, which are specialized structures formed during certain larval stages in nematodes. These proteins are implicated in cuticle assembly and attachment, ensuring the proper formation of the extracellular matrix that shields the organism from environmental challenges. Some family members contain small repeat motifs that are also found in proteins contributing to protective envelopes in various species.
Adhesion G protein-coupled receptor A (Adhesion_GPCR_A)
Type: Family

The Adhesion G protein-coupled receptor A family is involved in various signaling pathways and cellular processes. Members of the family function as receptors that play key roles in the planar cell polarity pathway, central nervous system vascularization, and the establishment of the blood-brain barrier. They act as coactivators of canonical Wnt signaling, assembling complexes essential for Wnt7-specific responses. Some members interact with extracellular matrix components and are implicated in cell adhesion and migration. The family includes orphan receptors whose precise functions are yet to be fully elucidated.
Multifunctional chaperone and stress response protein (Chaperone_stress_response)
Type: Family

This family of proteins includes co-chaperones that may interact with HSP70 and are implicated in ribosomal RNA biogenesis, particularly in the maturation of the 60S ribosomal subunit. Some members are involved in chromatin-related processes, such as position-effect variegation and chromosome condensation. Others function in cellular stress responses, including ER-phagy during ER stress, and in regulatory pathways affecting drug resistance. Common motifs such as the atg8-interaction motif and the FFAT motif suggest roles in protein-protein interactions, essential for their diverse functions.
Chromatin Regulation and Neuronal Gene Expression (ChromReg_NeuronalGeneExpr)
Type: Family

The protein family is involved in various aspects of chromatin regulation and neuronal gene expression. Members of the family are required for the correct progression through the G2 phase of the cell cycle and entry into mitosis, as well as for the repression of neuronal specific gene promoters mediated by RCOR1/CoREST. Other members play a role in neuronal differentiation, acting as chromatin-associated proteins. They can inhibit the effects of HMG20B, counteract the neuronal silencer REST, and activate neuronal-specific genes. Additionally, they are involved in the recruitment of the histone methyltransferase KMT2A/MLL1, leading to increased methylation of histone H3 lysine 4, which is a mark associated with active transcription.
RNA polymerase II-associated protein 3 (RPAP3)
Type: Family

The RPAP3 family proteins are implicated in forming an interface between the RNA polymerase II enzyme and chaperone/scaffolding proteins. They appear to play a crucial role in connecting RNA polymerase II to regulators of protein complex formation, which is essential for transcriptional regulation. Additionally, a member of the family in Schizosaccharomyces pombe is involved in meiosis, suggesting a possible role in cell division and differentiation. Another human family member is associated with cellular response to X-ray and regulates protein stability, indicating a broader functional spectrum that may include stress response and cell cycle control.
Krueppel C2H2-type Zinc-Finger Domain-Containing Protein (Krueppel_C2H2-ZF)
Type: Family

This family of proteins includes transcriptional regulators that bind to specific DNA motifs to activate or repress gene transcription. They play roles in various biological processes such as brown adipose tissue differentiation, thermogenesis, chondrocyte differentiation, neuron differentiation, cellular response to replication stress, and regulation of gene expression in response to retinoic acid. Members of this family are characterized by the presence of C2H2-type zinc-finger domains, which are crucial for DNA binding and interaction with other proteins such as SOX9. They are involved in the regulation of genes like UCP1, col2a1a, HMGN1, and SNCA, and can influence cell proliferation and survival.
Zinc finger homeobox transcription regulators (ZnFinger_Homeobox_TR)
Type: Family

The Zinc finger homeobox protein family is characterized by its role in transcriptional regulation, with diverse functions across its members. The family includes proteins that may influence neural and muscle differentiation, pain perception, and the processing of noxious stimuli. Some members act as transcriptional regulators with the ability to function as either activators or repressors. They are involved in various biological processes such as the inhibition of alpha-fetoprotein gene enhancers, regulation of circadian locomotor rhythms, myoblasts differentiation, repression of gastric cancer-associated genes, and modulation of cell cycle arrest genes in response to TGF-beta signaling. The family's involvement in embryonic central nervous system development is also noted, highlighting its significance in both developmental and physiological contexts.
Zinc-finger DNA-binding transcription regulators (Zinc-finger_DNA-bd_regulators)
Type: Family

This family of proteins includes transcription factors that bind to specific DNA sequences, often within enhancer elements of viral and cellular promoters. They are involved in various cellular processes including T-cell activation, transcriptional regulation, inflammation, and immune response. Members of this family can act as transcriptional activators or repressors and are known to interact with other proteins, such as TRAF2, to modulate signaling pathways. Some proteins within this family are also implicated in the regulation of cell growth, apoptosis, and bone formation. They typically contain zinc-finger motifs that facilitate DNA binding and may form dimers, tetramers, or higher-order structures to exert their regulatory functions.
Telomere Length Regulation TEL2 (TEL2_Regulation)
Type: Family

This family of proteins is involved in the regulation of the DNA damage response (DDR) and telomere length maintenance. Members of this family are components of the TTT complex, which is essential for stabilizing the levels of phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins. They contribute to the assembly, stabilization, and maintenance of TORC complexes that are critical for cell growth and survival in response to various signals. These proteins also play roles in genome stability, cell cycle arrest, apoptosis, and gene silencing at subtelomeric regions. They may interact with HSP90 to assist in the proper folding of newly synthesized PIKKs and are implicated in cellular resistance to DNA damage stresses such as ionizing radiation, ultraviolet light, and certain chemicals.
E3 ubiquitin-protein ligase PDZ domain-containing protein (E3_ubiquitin-PDZ_ligase)
Type: Family

This family of proteins includes E3 ubiquitin-protein ligases that play a role in protein ubiquitination, a post-translational modification essential for various cellular processes. Members of this family are involved in regulating the surface level of specific membrane proteins, such as MUSK, by mediating their ubiquitination and subsequent endocytosis and lysosomal degradation. This action is crucial for processes like myogenic differentiation. The family features a conserved RING-type zinc finger domain, which is necessary for their E3 ligase activity. Some members are also implicated in modulating ion channel currents by affecting the channel's plasma membrane presence.
Glutamate-rich WD repeat-containing (Glutamate-rich_WD_repeat)
Type: Family

The Glutamate-rich WD repeat-containing protein family is involved in various cellular processes related to chromatin dynamics and ribosome assembly. Members of the family function as histone-binding proteins that regulate chromatin structure and facilitate the loading of minichromosome maintenance (MCM) complexes at replication origins, potentially enhancing chromatin openness. Some family members are implicated in ribosome biogenesis, specifically in the early assembly of the 60S ribosomal subunit, by targeting ribosomal protein L3 onto precursor rRNA. Additionally, certain proteins within this family act as substrate receptors for CRL4 E3 ligase complexes, negatively regulating thermotolerance by affecting HSP90-1 function and the expression of heat-inducible genes.
tRNA Anticodon Loop Methyltransferase Regulator (tRNA_Anticodon_Mtase-Reg)
Type: Family

This family of proteins is involved in the post-transcriptional modification of tRNA molecules. Members of this family function in partnership with specific methyltransferases to methylate the 2'-O-ribose of nucleotides at the 34th position of the tRNA anticodon loop. This methylation is crucial for the correct positioning of the substrate tRNA during the modification process. Additionally, these proteins have roles in cellular processes such as the suppression of autophagy induced by amino acid starvation and the enhancement of cell growth suppression activities mediated by certain kinases. Some members also participate in the regulation of the retromer complex, which is important for the recycling of plasma membrane proteins from endosomes, and may be involved in the regulation of transposable elements.
Poly(U)-binding-splicing regulator (PUF60_regulator)
Type: Family

This family of proteins is involved in nuclear processes such as pre-mRNA splicing, transcription regulation, and apoptosis. They act as DNA- and RNA-binding proteins, regulating MYC transcription in association with FUBP1 through the core-TFIIH basal transcription factor. They can function as transcriptional repressors and modulate alternative splicing of mRNAs. These proteins are known to bind to relaxed DNA of active promoter regions, the pyrimidine tract, and 3'-splice site regions of pre-mRNA, with enhanced binding in the presence of U2AF2. They also interact with Y5 RNA in association with RO60 and bind to poly(U) RNA. Additionally, they may be involved in homodimerization and protein-protein interactions through their atypical third RNA recognition motif, known as the PUMP domain.
Mitochondrial Large Ribosomal Subunit mL45 (mtLSU_mL45)
Type: Family

This family of proteins is involved in the assembly and function of the mitochondrial ribosome, which is responsible for protein synthesis within mitochondria. These proteins are part of the large ribosomal subunit and are specific to mitochondria, indicating a specialized role in the translation of mitochondrial-encoded mRNAs. The mitochondrial ribosome is distinct from cytoplasmic ribosomes in its protein composition and is adapted to the unique environment of the mitochondrion. Proteins in this family are essential for the proper functioning of the mitochondrial ribosome and, by extension, for mitochondrial protein synthesis, which is critical for the organelle's role in energy production and other specialized functions.
Synaptopodin domain-containing protein (Synaptopodin_domain)
Type: Family

This family of proteins is involved in the regulation of cell migration and actin cytoskeleton dynamics. Members of this family have actin-binding and actin-bundling activities, which contribute to the formation of various actin structures such as stress fibers, lamellipodia, and actin networks. These proteins are implicated in the assembly and stabilization of sarcomeric Z lines in muscle cells and may interact with components of the autophagy machinery, suggesting a role in autophagosome formation. Some family members are associated with synaptic plasticity, indicating a potential role in modulating the shape and motility of dendritic spines and podocyte foot processes. Additionally, there is evidence suggesting a tumor suppressor function for certain members of this family.
Rab11-interacting regulator of endocytosis and ciliogenesis (Rab11-interacting_regulator)
Type: Family

This family of proteins acts as downstream effectors for Rab11 GTPase, playing a crucial role in endocytic trafficking and ciliogenesis. They are involved in membrane delivery and the movement of sorting endosomes along microtubules to generate the endocytic recycling compartment. These proteins facilitate dynein motor complex interactions and processivity, and are implicated in cytokinesis, particularly in abscission. They participate in the assembly of ciliary targeting complexes, contributing to ciliogenesis initiation and the transport of sensory receptors. Some members may influence actin cytoskeleton regulation, impacting cell motility, and may be involved in retinal development. The presence of an RBD-FIP domain is characteristic, mediating interactions with Rab11.
Rho GTPase-activating domain-containing protein (Rho-GAP_domain)
Type: Family

This family of proteins includes Rho GTPase-activating proteins (GAPs) that regulate the Rho family of GTPases. Members of this family are involved in various cellular processes such as cell differentiation, adhesion, migration, and morphogenesis of tissues like the retina and cerebral hemispheres. They play roles in axon outgrowth, guidance, and fasciculation, as well as in the regulation of F-actin polymerization and assembly. These proteins are also implicated in polarized cell migration, ciliogenesis, and mammary gland development. Some family members have a pseudoGTPase domain that does not bind GTP, while others have a functional N-terminal GTPase domain essential for proper cellular localization. The activity of these proteins can be modulated by binding to acidic phospholipids and phosphorylation by specific kinases. Additionally, certain members may repress transcription of specific genes, although this function requires further validation.
B-box zinc finger domain-containing protein (B-box_zinc_finger)
Type: Family

This family of proteins includes transcription factors that are primarily involved in the regulation of seedling photomorphogenesis. Members of this family act as either positive or negative regulators of this process, influencing various aspects such as hypocotyl elongation, chloroplast biogenesis, and responses to light and hormonal signals. Some proteins interact with key components like COP1 and HY5 to modulate gene expression related to light perception and signaling pathways. Additionally, certain members are implicated in the shade avoidance syndrome, brassinosteroid responses, UV-B responses, salt-stress response, and thermotolerance. Collectively, these proteins play crucial roles in plant development and adaptability to environmental cues.
WD repeat domain-containing protein MORG1 (WD_repeat_MORG1)
Type: Family

This family of proteins functions as molecular scaffolds for various multimeric protein complexes. They play a role in the assembly of scaffolds for the ERK signaling pathway, modulating ERK activation in response to specific stimuli. These proteins can either enhance or inhibit ERK activation depending on their concentration. Additionally, they are involved in cellular response to hypoxia, often acting as negative regulators of the HIF1A transcription factor, potentially promoting its degradation. Some family members are implicated in the recruitment of signaling complexes to upstream activators and may participate in pre-mRNA splicing processes.
Glycosyltransferase 32 (Glycosyltransf_32)
Type: Family

The glycosyltransferase 32 family is involved in the biosynthesis of glycosphingolipids, which are essential components of mammalian cell membranes. Members of this family catalyze the transfer of sugar moieties from nucleotide sugars to acceptor molecules, forming various glycosidic linkages. Specifically, lactosylceramide 4-alpha-galactosyltransferases from this family add galactose to lactosylceramide to produce globotriaosylceramide (Gb3Cer), a key glycosphingolipid in the globo series. Gb3Cer serves as the Pk antigen in blood histogroup P and is a receptor for bacterial verotoxins. Another enzyme, alpha-1,4-N-acetylglucosaminyltransferase, transfers N-acetylglucosamine to O-glycans, contributing to the synthesis of type III mucin in the gastrointestinal tract, which may offer protection against gastric adenocarcinoma. The conserved DXD motif within these enzymes is crucial for their catalytic activity.
Ciliary Assembly and Mitochondrial Import (CiliaryAsmbly_MitoImport)
Type: Family

The protein family is involved in distinct cellular processes. Some members play a role in the cytoplasmic assembly and/or trafficking of ciliary or axonemal dynein arms, which are essential for ciliary and flagellar movement, and may be implicated in fertilization. These members also exhibit GTPase activity. Other members of the family are involved in mitochondrial protein import, acting as receptors in the mitochondrial membrane for cytosolically synthesized preproteins. They bind mature portions of precursor proteins, may interact with cellular components, and display weak ATPase activity, potentially functioning as chaperone-like proteins to maintain precursors in an unfolded state suitable for import.
WD repeat and SOCS box domain-containing protein (WSB_SOCS-box_domain)
Type: Family

This family of proteins includes components that are likely involved in ubiquitination and proteasomal degradation pathways. They are thought to act as substrate-recognition parts of SCF-like ECS E3 ubiquitin ligase complexes. These complexes play a crucial role in targeting specific proteins for ubiquitination, marking them for degradation by the proteasome. The presence of a SOCS box domain suggests these proteins interact with the Elongin BC complex, which is an adapter for various E3 ubiquitin ligase complexes. Some family members are known to recognize specific substrates such as type II iodothyronine deiodinase/DIO2 and may regulate the stability of other proteins like HIPK2 through proteasomal degradation.
Alsin GEFs and Motor Neuron Regulators (Alsin_GEFs/MotNeuronReg)
Type: Family

The Alsin family proteins function primarily as guanine nucleotide exchange factors (GEFs) for Rab5 GTPase, a key regulator in endosomal trafficking. By catalyzing the exchange of GDP for GTP on Rab5, members of the Alsin family convert it from an inactive to an active state, thus regulating endosome dynamics. Additionally, Alsin proteins are implicated in the control of survival and growth of spinal motoneurons. These functions are crucial for maintaining proper neuronal function and may have implications in neurodegenerative diseases where motor neuron survival is compromised.