SII-SWORD/CoKE huggingface dataset:
LZTR1/Attractin (LZTR1/Attractin)
Type: Family

The LZTR1/Attractin family includes proteins that are involved in various cellular processes. LZTR1 proteins act as substrate-specific adapters for BCR E3 ubiquitin-protein ligase complexes, targeting Ras proteins for ubiquitination and thereby negatively regulating RAS-MAPK signalling . This function is crucial for controlling Ras levels and membrane association, impacting cell growth and differentiation. Attractin and its homologues, on the other hand, are implicated in immune response, chemotactic activity of chemokines, melanocortin signalling pathways, energy homeostasis, hair color, and myelination in the central nervous system . They may also serve as low-affinity receptors for agouti.
SH3 and multiple ankyrin repeat domains protein (SHANK)
Type: Family

This family of proteins functions as scaffolding components in the postsynaptic density (PSD) of excitatory synapses, playing a crucial role in the organization and maintenance of synaptic structure and function. They interact with various receptors on the postsynaptic membrane, including NMDA-type and metabotropic glutamate receptors, and link them to the actin cytoskeleton. These interactions are mediated through complexes with other synaptic proteins such as GKAP/PSD-95 and Homer. Members of this family are involved in the maturation of dendritic spines, synaptic transmission, and plasticity, and they regulate actin dynamics, which is essential for neuron growth cone motility and synaptic signaling pathways.
TBC1 domain family involved in cilium biogenesis (TBC1_cilium_biogenesis)
Type: Family

The TBC1 domain family is involved in cilium biogenesis and functions as a molecular adapter. It is part of a complex that includes the centriolar protein OFD1, which is essential for cilium assembly. Members of the family may regulate the cAMP-dependent phosphorylation of OFD1, leading to its ubiquitination by PJA2 and subsequent proteasomal degradation. Additionally, some members are implicated in ribosome biogenesis, particularly in the nucleolar processing of pre-18S ribosomal RNA as part of the small subunit processome.
Nuclear receptor corepressor (N-CoR_corepressor)
Type: Family

This family of proteins functions as transcriptional corepressors for nuclear receptors. They are involved in chromatin condensation, which restricts access of basal transcription machinery to DNA, thereby repressing gene expression. Members of this family contain conserved CORNR box motifs that are essential for binding to unligated nuclear hormone receptors. Flanking sequences of the CORNR box determine specificity for different nuclear receptors. These proteins are implicated in various biological processes including the regulation of circadian rhythm, lipid metabolism in the liver, and cellular proliferation. They participate in complexes that promote histone deacetylation, contributing to the formation of repressive chromatin structures. Additionally, they play roles in the regulation of B-cell proliferation and survival within germinal centers, and are involved in androgen receptor signaling.
Vacuolar Transporter Chaperone Complex Subunit (VTC_Complex_Subunit)
Type: Family

This family of proteins functions as subunits of the vacuolar transporter chaperone (VTC) complex, which is involved in the synthesis and translocation of inorganic polyphosphate (polyP). The complex catalyzes the transfer of phosphate from ATP to a growing polyP chain, releasing ADP, and integrates cytoplasmic polymer synthesis with polyP membrane translocation. The complex contains multiple vacuolar transmembrane domains that likely form a channel for polyP transport into the vacuole lumen. This process is dependent on the proton gradient across the membrane. Additionally, these proteins play a role in vacuolar membrane fusion and are involved in various cellular processes such as microautophagy, SNARE priming, and the regulation of cytosolic phosphate concentrations through binding to inositol polyphosphates. The SPX domain present in some subunits has a high affinity for inositol polyphosphates and may integrate signaling to adapt phosphate concentrations.
Ankyrin repeat and SOCS box domain-containing protein (Ankyrin-SOCS_box_domain)
Type: Family

This family of proteins includes components that may act as substrate-recognition modules within SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complexes. These complexes are involved in the ubiquitination and subsequent proteasomal degradation of target proteins, which is a critical process in regulating various cellular functions. Some members of this family are implicated in the initiation of arteriogenesis. The presence of ankyrin repeats suggests a role in protein-protein interactions, while the SOCS box domain is essential for binding to the Elongin BC complex, which is a part of the E3 ubiquitin ligase complex.
Zinc finger E-box-binding homeobox (ZnF_E-box_Homeobox)
Type: Family

The Zinc finger E-box-binding homeobox family comprises transcription factors that play critical roles in gene expression regulation. Members of this family typically function as transcriptional repressors, binding to E-box sequences in gene promoters to modulate transcription. They are involved in various biological processes including epithelial-mesenchymal transition (EMT), neuronal differentiation, and cell migration. Some members also act as transcriptional activators, regulating genes essential for cell cycle progression and DNA damage response. The family is characterized by the presence of C2H2-type zinc-finger domains, which facilitate DNA binding, and a homeobox domain, indicative of their role in development and differentiation.
Myb-like DNA-binding (Myb-like_DNA-bd)
Type: Family

The Myb-like DNA-binding protein family is characterized by its role in transcriptional regulation across various organisms. Members of this family are involved in activating transcription of genes associated with specific biological processes, such as histidine biosynthesis, purine biosynthesis, fruiting body formation, and cell differentiation. Some proteins within this family are part of the SNAPc complex, essential for snRNA gene transcription, and bind to promoter elements to recruit transcriptional machinery. Others act as transcriptional activators that regulate genes critical for multicellular development, cellular differentiation, and cell cycle regulation, particularly in the context of the parasite erythrocytic cycle. The family exhibits a diverse range of functions, including the regulation of azasperpyranone A biosynthesis and the expression of non-coding RNAs and transfer RNA genes.
PX Domain-Containing Rho GAP (PX-Rho_GAP)
Type: Family

The PX domain-containing GAP family is characterized by its involvement in the regulation of small GTPases such as RHOA, CDC42, and RAC1. Members of this family function as GTPase-activating proteins (GAPs), promoting GTP hydrolysis and thus regulating the activity of their target GTPases. These proteins play critical roles in various cellular processes, including intracellular trafficking, glucose transport regulation, neuronal cell differentiation, dendritic spine actin reorganization, and cell migration. The N-terminal PX domain of these proteins specifically interacts with phosphatidylinositides, which is essential for their localization and function within the cell. The family's involvement in cross-talk between Ras- and Rho-regulated signaling pathways highlights its importance in cell growth regulation.
Myelin Regulatory Factor-like (MRF-like)
Type: Family

This family of proteins includes transcription factors that are key regulators in the maturation and maintenance of the nervous system, particularly in the formation of myelin, which is essential for proper nerve conduction. Members of this family are involved in the activation of gene expression related to myelin production during the maturation of oligodendrocytes. They have a characteristic peptidase S74 domain that mediates autocatalytic cleavage, releasing an N-terminal component that acts as the active transcription factor, while the C-terminal part remains membrane-bound with no transcriptional activity. These proteins are also implicated in synaptic rewiring during nervous system development, indicating a broader role in neuronal function.
Glycerophosphodiester Phosphodiesterase (GDPD)
Type: Family

This family of proteins includes enzymes with glycerophosphodiester phosphodiesterase activity, which are involved in the metabolism of glycerophospholipids. They hydrolyze glycerophosphocholine to glycerol-phosphate and choline, a process important for the synthesis of phosphatidylcholine and the utilization of glycerophosphocholine as a phosphate source. Some family members may also hydrolyze other glycerophosphodiesters, such as glycerophosphoinositol and glycerophosphoethanolamine. Additionally, certain proteins within this family are implicated in the regulation of skeletal muscle differentiation, independent of their enzymatic activity.
DNA Damage Response and Transcriptional Regulator (DDR_Transcriptional_Reg)
Type: Family

The protein family is involved in the DNA damage response (DDR) and transcriptional regulation. Members of the family function as mediators and scaffolds at sites of DNA damage, recognizing and binding to specific phosphorylated histone markers, such as H2AX phosphorylated at 'Ser-139'. They facilitate the recruitment of DNA repair and signal transduction proteins, contributing to cell cycle arrest, kinase activation, and chromosomal stability during mitosis. Some family members also interact with histone methyltransferase (HMT) complexes, influencing transcriptional regulation and playing roles in early development. The family is associated with the repair of double-strand breaks (DSBs) through homologous recombination and may regulate the recruitment of polymerase eta and RAD51 post-DNA damage. Additionally, they are implicated in transcriptional regulation during immunoglobulin class switching in B-cells and may act as transcriptional cofactors in TGF beta signaling.
Zinc finger and chromatin remodeling-associated protein (ZnF-Chromatin_assoc)
Type: Family

This family of proteins includes transcription factors and components of multiprotein complexes involved in chromatin remodeling and transcriptional regulation. They play roles in various biological processes including ribosome biogenesis, cell cycle progression, myeloid and lymphoid cell development, and neural development. Some family members are involved in metabolic regulation, influencing lipid metabolism, glucose homeostasis, and insulin sensitivity. They interact with modified histones, indicating a role in epigenetic regulation. The presence of zinc finger domains suggests DNA-binding capabilities, and some members are implicated in the regulation of gene expression in response to environmental cues and stress.
Calcium-Binding Signalling family (Ca-bind)
Type: Family

Calcium binding signalling proteins are characterised by their ability to bind calcium, which suggests a role in cellular signalling events. While some members are hypothesised to function as regulatory proteins rather than as calcium buffers or transport proteins, the exact mechanisms by which they influence signalling pathways remain to be fully elucidated. The potential regulatory function implies that these proteins may interact with other cellular components to modulate processes that are sensitive to calcium levels, which is a common second messenger in many signalling cascades. These proteins usually contain EF-hand domains .
Leucine-rich repeat extensin-like regulator (LRR_extensin-like_regulator)
Type: Family

This family of proteins is involved in the modulation of cell morphogenesis. They play a crucial role in the regulation of cell wall formation, assembly, and growth polarization. Some members of this family are specifically expressed in pollen, while others are implicated in root hair morphogenesis and elongation. These proteins are characterized by the presence of leucine-rich repeat (LRR) domains, which are typically involved in protein-protein interactions, and extensin-like regions that may be associated with the cell wall structure and function.
Yes-associated protein 1 (YAP1)
Type: Family

The YAP1 family comprises transcriptional regulators that function as coactivators or corepressors. They are essential components of the Hippo signaling pathway, which is crucial for controlling organ size, suppressing tumors, and regulating apoptosis and proliferation. Family members mediate tissue tension and 3D tissue shape by influencing the cortical actomyosin network. They interact with TEAD transcription factors and are involved in various cellular processes, including cell contact-mediated growth control, epithelial-mesenchymal transition, and ciliogenesis suppression. Some members also play roles in neural plate development, stress response, and aging.
GPCR-associated LMBR1 domain-containing protein (GPCR-associated_LMBR1)
Type: Family

This family of proteins is associated with G-protein coupled receptors (GPCRs) and is implicated in the regulation of downstream signaling pathways. Members of this family are known to interact with specific GPCRs, such as the beta-2 adrenergic receptor and the type-1 angiotensin II receptor, and can negatively regulate signaling pathways initiated by these receptors. The regulatory function of these proteins suggests a role in modulating receptor-mediated cellular responses.
STE20 Subfamily Serine/Threonine Kinases (STE20_Ser/Thr_Kinases)
Type: Family

This family of proteins includes serine/threonine kinases that are part of the STE20 subfamily within the protein kinase superfamily. Members are involved in various cellular processes, including the regulation of lymphocyte migration through phosphorylation of cytoskeletal proteins such as MSN and ERM proteins. Some act as polo kinase kinases, potentially mediating the phosphorylation and activation of PLK1, which plays a role in cell cycle regulation. Additionally, certain members are implicated in apoptosis and the dissolution of actin stress fibers. The activity of these kinases can be modulated by specific inhibitors, indicating their potential as therapeutic targets.
Protein kinase C-binding NELL (PKC-binding_NELL)
Type: Family

The NELL protein family is involved in a range of biological processes primarily related to neural and bone tissue functions. Members of the family play crucial roles in cell growth, differentiation, and survival, with specific emphasis on promoting osteoblast differentiation and mineralization, as well as regulating neuronal proliferation and axon guidance. In neural tissues, they are essential for neuronal polarization, synaptic functions, and the development of axons through the MAPK signaling pathway. They interact with receptors like ROBO3 to guide axons and contribute to neuron survival. Additionally, they are involved in the regulation of hypothalamic GNRH secretion, influencing puberty control. Some members also have roles in the male reproductive system, regulating sperm maturation and fertility through signaling pathways such as the ROS1-pathway. Furthermore, certain proteins within this family can act as inhibitors of PRKCB in glial cells.
Adhesion G-protein coupled receptor (Adhesion_GPCR)
Type: Family

This family of proteins includes receptors that are known to play a critical role in lung surfactant homeostasis and may also influence adipocyte function. Several members of this family are described as orphan receptors, indicating that their endogenous ligands or functions have not yet been identified. All proteins in this family belong to the G-protein coupled receptor 2 family and are part of the Adhesion G-protein coupled receptor (ADGR) subfamily, which is characterized by a long N-terminus with various adhesion domains that facilitate cell-cell and cell-matrix interactions.
Eukaryotic Cobalamin Transport (Cobalamin_Transport)
Type: Family

This family of proteins is involved in the binding and transport of cobalamin, also known as vitamin B12. Members of this family are responsible for the protection of cobalamin from the acidic environment of the stomach and its delivery to cells. They exhibit high-affinity binding to cobalamin and are essential for its absorption in the ileum. The transport process involves receptor-mediated endocytosis, often after interaction with specific receptors such as CUBN. These proteins play a crucial role in the cellular uptake of vitamin B12, which is vital for various metabolic processes including DNA synthesis and red blood cell formation.
Sialate:O-sulfotransferase (Sialate-O-sulfotransferase)
Type: Family

This family of proteins includes enzymes that function as sialate:O-sulfotransferases. These enzymes are responsible for catalyzing the 8-O-sulfation of Sia-glycans using 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as a sulfate donor. The resulting 8-O-sulfated Sia (Sia8S)-glycans have implications in various biological processes, including cell-cell communication and pathogen interaction. Members of this family share a common enzymatic activity despite being found across different species, indicating a conserved function in glycan modification.
DNA Replication Regulatory Kinase Subunit (Replication_Regulatory_Kinase)
Type: Family

This family of proteins includes regulatory subunits for kinases involved in DNA replication and cell cycle progression. Members of this family activate kinase activity essential for the initiation and regulation of DNA replication. They are involved in phosphorylating components of the pre-replication complex, particularly the MCM2 subunit, which is crucial for the unwinding of DNA and the beginning of replication. These proteins are required for the transition from G1 to S phase and play roles in cell proliferation. Some members also have functions in meiosis, sporulation, and checkpoint control in response to DNA damage or replication stress. Additionally, variations in these proteins are implicated in different developmental stages and cellular responses to replication challenges.
UPF0224 (FAM112) RNA Processing (UPF0224_FAM112_RNA_Proc)
Type: Family

The UPF0224 (FAM112) family includes proteins involved in various aspects of RNA processing and regulation of gene expression. Members of this family are implicated in the recognition of U12-type 5' splice sites, suggesting a role in the splicing of minor class introns. Some proteins within the family, such as Gametocyte-specific factor 1 (GTSF1) and its homologs, are essential for spermatogenesis and act in the suppression of retrotransposon transcription in male germ cells. They are thought to function through the piRNA pathway, contributing to the repression of transposable elements during meiosis and the methylation of transposons. This indicates a broader involvement in the maintenance of genomic integrity in reproductive cells. Other members are required for oocyte maturation, indicating a role in female reproductive processes as well. The presence of zinc finger domains in some family members suggests a potential for DNA or RNA binding, which is consistent with their roles in transcriptional regulation and RNA processing.
HERV-K(HML-2) Pro peptidase A2 (HERV-K_Pro_peptidase_A2)
Type: Family

The HERV-K(HML-2) Pro peptidase A2 family consists of endogenous retroviral proteases that are derived from the human endogenous retrovirus group K. These proteins are implicated in the processing of primary translation products and the maturation of viral particles. During evolution, the endogenous Pro proteins may have retained, lost, or modified their original retroviral functions. Some members of this family have preserved most of the characteristics typical of retroviral proteases, while others may exhibit variations in activity, including resistance or susceptibility to certain inhibitors. The family's role reflects the complex interplay between endogenous retroviral elements and their host genomes, contributing to the understanding of viral evolution and the molecular history of retroviral integration into human DNA.
Ergosterol Biosynthesis ERG27 Subfamily (Ergosterol_Biosynth_ERG27)
Type: Family

The ERG27 subfamily of the short-chain dehydrogenases/reductases (SDR) family is involved in the ergosterol biosynthesis pathway, particularly in the reduction of the keto group on the C-3 of sterols. Members of this family function as 3-keto-steroid reductases and are catalytic components of the C-4 demethylation complex. This complex is part of the late steps of ergosterol synthesis, which mainly occurs in the endoplasmic reticulum membrane. The ergosterol biosynthesis pathway is crucial for the production of ergosterol, an essential component of fungal cell membranes. The ERG27 subfamily proteins facilitate the conversion of sterol intermediates, such as 4,4-dimethylfecosterol, into fecosterol via 4-methylfecosterol, ultimately leading to the production of ergosterol. This process involves a series of demethylation, reduction, and desaturation reactions that are vital for maintaining cell membrane integrity and function in fungi.
KRIT1/FRMD8 (KRIT1/FRMD8)
Type: Family

This family of proteins includes Krev interaction trapped protein 1 (KRIT1), its paralogue FERM domain-containing protein 8 (FRMD8) and closely related proteins. Members of this entry are involved in various cellular processes, including the stabilisation of cell surface proteins, regulation of signaling pathways, and maintenance of cellular homeostasis.

FRMD8 promotes the stability of iRhom1/RHBDF1 and iRhom2/RHBDF2, preventing their degradation and facilitating ADAM17-mediated shedding of ligands such as TNF and growth factors . They also play a role in negatively regulating Wnt signaling .

KRIT1 is part of the CCM signaling pathway, crucial for cardiovascular development, acting as negative regulators of angiogenesis and influencing endothelial cell functions . They interact with integrins and participate in maintaining intracellular reactive oxygen species homeostasis, which is essential for preventing oxidative damage and modulating cell proliferation [

, . Additionally, they are involved in the regulation of macroautophagy and cellular polarity through interactions with various proteins and signaling cascades . Mutations in this proteins are related to cerebral cavernous malformations.
Glycosyl Hydrolase 25 Enzymes (GH25_Enzymes)
Type: Family

This family of proteins is characterized by glycosyl hydrolase activity, specifically within the glycosyl hydrolase 25 family. Members of this family are involved in various biological processes, including the stress response to heavy metals, limiting the size of multicellular structures during aggregation, and providing resistance to bacterial infections. Some proteins in this family have been noted to have antibacterial activity against Gram-positive bacteria and are implicated in the immune response to both Gram-positive and Gram-negative bacterial infections. Additionally, a role in fungal defense has been suggested for some members. The functions of these proteins seem to be diverse, ranging from enzymatic activity to involvement in cellular and organismal defense mechanisms.
Caulimoviridae Movement (Caulimoviridae_Movement)
Type: Family

The Caulimoviridae movement protein family is responsible for the intercellular transport of viral genomes in plant cells. These proteins facilitate the cell-to-cell propagation of viral particles by modifying plasmodesmata to allow the passage of viral ribonucleocapsids. They achieve this by forming tubule structures that increase the size exclusion limit of plasmodesmata, effectively bypassing the host cell wall barrier. This mechanism is crucial for the efficient spread of the virus without the need for viral budding, ensuring the movement of the viral genome directly to adjacent cells.