SII-SWORD/CoKE huggingface dataset:
Endoplasmic reticulum disulfide reductase (ER_disulfide_reductase)
Type: Family

This family of proteins functions as endoplasmic reticulum disulfide reductases, playing a crucial role in protein homeostasis. They are involved in the correct folding of nascent proteins by catalyzing the reduction of non-native disulfide bonds, as well as in the degradation of misfolded proteins through the endoplasmic reticulum-associated degradation pathway. These proteins interact with molecular chaperones to facilitate substrate release and are implicated in the apoptotic signaling pathway in response to endoplasmic reticulum stress. Notably, they contain thioredoxin domains, with some regions lacking the redox-active CXXC motif.
EVA1 A/B (EVA1_A/B)
Type: Family

This entry represents the EVA1 A and B. EVA1A, also known as TMEM166, regulates cell autophagy and apoptosis, which are essential for maintaining cellular homeostasis and responding to cellular stress . EVA1A has also been shown to promote papillary thyroid cancer progression and epithelial-mesenchymal transition via upregulating immune-related signaling pathways . EVA1 play a pivotal role in these pathways, ensuring the proper execution of cell death mechanisms that are vital for organismal development and the prevention of disease.
SRA stem-loop-interacting RNA-binding protein/Glycine-rich RNA-binding-like (SLIRP/GR-RBP-like)
Type: Family

This family comprises RNA-binding proteins with roles in RNA transcription or processing, particularly under stress conditions . Some members of the family are involved in C-to-U editing of mitochondrial RNA, with some controlling a significant proportion of mitochondrial editing sites . They exhibit a strong affinity for single-stranded nucleic acids, especially poly(U) sequences. SLIRP functions as a nuclear receptor corepressors by interacting with specific RNA structures, such as the SRA RNA, to modulate nuclear receptor coactivation . These proteins are implicated in stress tolerance mechanisms and may influence transcriptional regulation through their RNA-binding capabilities.
O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase (O-linked_mannose_GnT)
Type: Family

This family of proteins participates in the post-translational modification process known as O-mannosyl glycosylation. Members of this family are responsible for catalyzing the transfer of N-acetylglucosamine to O-linked mannose residues on target glycoproteins. This enzymatic activity results in the synthesis of a specific glycan moiety, GlcNAc(beta1-2)Man(alpha1-)O-Ser/Thr, which is essential for the maturation of alpha-dystroglycan and other O-mannosylated proteins. The addition of this glycan structure provides a foundation for further carbohydrate modifications. These proteins contain a GG-type lectin domain, also referred to as the stem domain, which facilitates the specific recognition and interaction with beta-linked N-acetylglucosamine on substrates. The family is characterized by its membership in the glycosyltransferase 13 family, indicating a shared enzymatic function in glycan biosynthesis.
Synovial Proliferation Regulator (Synovial_Prolif_Regulator)
Type: Family

This family of proteins is involved in cellular responses to inflammatory stimuli. Members of this family are known to contribute to the proliferation of cells, particularly synovial fibroblasts, under such conditions. The role of these proteins is crucial in the regulation of inflammatory processes and may have implications in various physiological and pathological states where inflammation is a key factor.
Mitochondrial NAD+ Carrier (Mito_NAD+_Carrier)
Type: Family

This family of proteins includes mitochondrial membrane carrier proteins that are involved in the transport of nicotinamide adenine dinucleotide (NAD+) into the mitochondria. These proteins play a role in cellular metabolism by facilitating the import of NAD+, which is necessary for processes such as glycolysis and mitochondrial respiration. While the exact transport mechanism, whether it operates via uniport or antiport, as well as its electrogenicity and substrate selectivity, are yet to be fully characterized, it is known that some members of this family are essential for NAD+ import into mitochondria, whereas others are not.
DNA Methylation Protection Complex (DNA_MethProtect_Complex)
Type: Family

The protein family is involved in the protection and maintenance of transcriptional and developmental programs. It has a crucial role in safeguarding bivalent promoters and poised enhancers from hypermethylation, with a distinct preference for these regulatory elements. The family members function by forming a complex with TET1, binding to DNA, and preventing the binding of DNMT3A/3B, thus inhibiting de novo methylation. This activity is essential for the proper regulation of gene expression and the prevention of aberrant methylation patterns that could lead to developmental defects or diseases.
Sorting nexin PX domain-containing protein (Sorting_nexin_PX-domain)
Type: Family

This family of proteins is involved in intracellular trafficking, indicating a role in the transport and sorting of molecules within the cell. Members of this family are characterized by the presence of a PX domain, which is known to bind specifically to phosphatidylinositol 3-phosphate (PtdIns(P3)) enriched membranes. This lipid-binding ability suggests that these proteins may associate with endosomal membranes or other intracellular compartments where PtdIns(P3) is present, thereby influencing the localization and function of these proteins in cellular trafficking pathways.
Dual specificity MAP kinase kinase (Dual_spec_MAPK_kinase)
Type: Family

This family of proteins includes dual specificity mitogen-activated protein kinase kinases (MAP2Ks) that play a crucial role in the MAP kinase signal transduction pathway. They are essential components of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. These kinases are unique in their ability to directly activate the JNKs by phosphorylation, with specific preferences for phosphorylation sites within the Thr-Pro-Tyr motif. They are involved in various cellular processes, including the response to pro-inflammatory cytokines, apoptosis through the mitochondrial death signaling pathway, and transcriptional regulation in response to certain stimuli. Additionally, they are activated by phosphorylation by specific MAP kinase kinase kinases and contain conserved docking sites within their D and DVD domains for substrate and upstream kinase binding, respectively.
Meiosis-specific OB domain-containing (MEIOB)
Type: Family

The MEIOB family comprises single-stranded DNA-binding proteins that play a crucial role in meiosis, particularly in homologous recombination during meiosis I. Members of the MEIOB family are essential for the repair of double strand breaks (DSBs) and the formation of crossovers, which are vital for the accurate segregation of homologous chromosomes. These proteins are not involved in the initial loading of recombinases but are necessary to maintain an adequate number of RAD51 and DMC1 foci beyond the zygotene stage. The MEIOB family proteins may contribute to the stabilization of recombinases, facilitating successful homology search and meiotic recombination. Additionally, they exhibit 3'-5' exonuclease activity in vitro, which may be involved in the resolution of recombination intermediates into crossovers.
Endoplasmic Reticulum Stress-Regulated Transcription Factor (ER_Stress-Reg_TF)
Type: Family

This family of proteins functions as transcription factors during endoplasmic reticulum (ER) stress, regulating the unfolded protein response (UPR). They are involved in various developmental processes including cardiac myogenesis, hepatogenesis, and the development of secretory tissues. These proteins also play roles in B lymphocyte differentiation, immunoglobulin production, and cellular responses to ER stress. They contribute to angiogenesis and vascular development, modulate insulin resistance and glucose homeostasis, and are implicated in lipid metabolism and proteostasis. Additionally, they participate in the unconventional splicing of their own mRNA, which is essential for the production of active isoforms that can respond to ER stress. They are also involved in the regulation of apoptosis, autophagy, and the epithelial-to-mesenchymal transition in cancer cells. These proteins bind to various elements in gene promoter regions and are associated with several signaling pathways, including those mediated by PI(3)K, mTORC2, and Akt.
Protease B Inhibitor I9 (PBI_I9)
Type: Family

This family of proteins includes cytosolic inhibitors of vacuolar proteinase B, which are likely involved in regulating protease B activity during limited proteolysis. Members of this family are also components of the LMA1 complex, which plays a role in facilitating vesicle fusion processes, including homotypic vacuole fusion and the fusion of ER-derived COPII vesicles with the Golgi apparatus.
MORN repeat-containing protein 3 (MORN3)
Type: Family

This family of proteins is involved in the regulation of the tumor suppressor p53/TP53 through the assembly of a suppression complex. The proteins in this family function by tethering the enzymes SIRT1 and MDM2 to p53/TP53, leading to its deacetylation-mediated functional inactivation and ubiquitination-dependent degradation. This dual regulatory mechanism promotes cellular proliferation and survival. Additionally, these proteins may have a role in the regulation of spermatogenesis.
Mitochondrial Large Ribosomal Subunit mL53 (mtLSU_mL53)
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 play a role in the translation of mitochondrial-encoded mRNAs, essential for the production of components of the respiratory chain and ATP synthesis. As mitochondria-specific ribosomal proteins, they are distinct from their cytoplasmic counterparts and are adapted to the unique environment of the mitochondrion, including its genome and the polycistronic nature of its mRNAs.
UDP-N-acetylglucosamine transferase subunit (UDP-GlcNAc_transferase)
Type: Family

This family of proteins includes UDP-N-acetylglucosamine transferase subunits that are essential components in the pathway of protein N-glycosylation. They play a crucial role in the second step of the dolichol-linked oligosaccharide pathway, which is a fundamental process for the proper folding and stability of many proteins. Members of this family are characterized by their enzymatic activity as part of the glycosyltransferase 28 family, catalyzing the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to dolichol-phosphate.
Wnt Signal Transduction Protein (Wnt_Signal_Transd_Protein)
Type: Family

This family of proteins is involved in the Wnt signaling pathway, a critical mechanism for regulating gene expression and cell behavior. Members of this family play a role in transmitting signals received from Wnt proteins to the intracellular environment, influencing various developmental processes and cell fate decisions. The proteins in this family are characterized by their participation in the transduction of Wnt signals, which is essential for proper embryonic development, cell proliferation, and differentiation. Dysregulation of the Wnt pathway can lead to a variety of diseases, including cancer.
Ubiquitin-associated domain-containing protein 1 (UBAC1)
Type: Family

This entry represents UBAC1 and related proteins found in eukaryotes.

Ubiquitin-associated domain-containing protein 1 (UBAC1) proteins include non-catalytic components of the KPC complex, a specific type of E3 ubiquitin-protein ligase complex. Members of this group function as adaptors within the KPC complex, facilitating the transfer of polyubiquitinated target proteins to the 26S proteasome for degradation. These proteins are involved in the polyubiquitination of key regulatory proteins such as CDKN1B, which plays a role in cell cycle control, and NFKB1, a component of the NF-kappa-B signalling pathway. The ubiquitin-associated (UBA) domains present in these proteins are responsible for recognising and binding polyubiquitinated substrates, indicating a role in targeting proteins for proteasomal degradation, which is essential for various cellular processes, including cell cycle progression and signal transduction .
Orphan G-protein coupled receptor 1 (Orphan_GPCR1)
Type: Family

This family of proteins includes G-protein coupled receptors (GPCRs) that are classified as orphan receptors, which means their endogenous ligands have not been identified. Members of this family are thought to signal through a G(q/11)-mediated pathway, although the specific biological processes they regulate remain to be elucidated. As GPCRs, they are likely involved in transducing extracellular signals into intracellular responses, a characteristic function of receptors in this superfamily.
Transcriptional Regulators of Metabolite Synthesis (Metabolite_Synth_Reg)
Type: Family

This family of proteins includes transcription factors and probable transcriptional repressors. Members are involved in the regulation of gene clusters responsible for the biosynthesis of specific secondary metabolites, such as kojic acid, which is a by-product of the fermentation process and acts as a chelation agent. Some proteins within this family are known to bind specific nucleotide sequences to control the expression of genes, including those related to multidrug resistance. The regulatory activities of these proteins are crucial for various cellular processes, including the response to different carbon sources and the control of multidrug resistance gene expression.
GPI-anchored Adhesion Regulator (GPI-anchor_Adhesion_Reg)
Type: Family

This family of proteins includes GPI-anchored membrane proteins that are implicated in cell adhesion processes. Members of this family are involved in the formation of biofilms and may play roles in virulence by mediating cell-cell and cell-substrate interactions. The presence of serine/threonine-rich regions suggests potential post-translational modification sites that could be important for their function.
Receptor-associated synaptic protein (RAPsyn)
Type: Family

This family of proteins is involved in the postsynaptic clustering of nicotinic acetylcholine receptors at the neuromuscular junction. Members of this family may interact with the postsynaptic cytoskeleton, potentially through direct association with actin or spectrin. They contain a cysteine-rich region that is homologous to part of the regulatory domain of protein kinase C, which may play a role in lipid bilayer interactions.
Double zinc ribbon and ankyrin repeat-containing protein (DZAN1)
Type: Family

This family of proteins is involved in the intracellular transport of organelles and vesicles, particularly within photoreceptor cells. Members of this family play a crucial role in the formation, maintenance, and function of the photoreceptor's outer segments, which are essential for the conversion of light into electrical signals in the visual pathway.
Mitochondrial large ribosomal subunit mL37 (mtLSU_mL37)
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 the mitochondria, reflecting their specialized roles in mitochondrial gene expression. The mitochondrial ribosome is adapted to synthesize a distinct set of proteins encoded by the mitochondrial genome, which are essential for the organelle's energy-producing processes. As such, members of this protein family are integral to the maintenance of mitochondrial function and cellular energy metabolism.
Basic leucine zipper transcription regulators (bZIP_transcription_regulators)
Type: Family

This family of proteins includes transcriptional activators and regulators. Members of this family are involved in various cellular processes, including the control of cell wall patterning, pollen development, metabolic pathways, cellular transport, and lipid metabolism. They share a basic leucine zipper domain, which is typically involved in DNA binding and dimerization, essential for their function as transcription factors.
Centromere Protein W/WIP1 (CENP-W/WIP1)
Type: Family

The CENP-W/WIP1 family is involved in the essential processes of kinetochore assembly, mitotic progression, and chromosome segregation. Family members are components of the CENPA-NAC complex, which is crucial for assembling kinetochore proteins and may assist in the integration of newly synthesized CENPA into centromeres. They also form part of a nucleosome-associated complex that preferentially binds to histone H3-containing nucleosomes at the centromere. Additionally, they are constituents of the heterotetrameric CENP-T-W-S-X complex that binds and supercoils DNA, significantly contributing to kinetochore structure. These proteins are inner kinetochore proteins, foundational for kinetochore function and necessary for proper chromosome organization and progression through mitosis.
MEGF-related differentiation regulators (MEGF_diff_regulators)
Type: Family

This family of proteins includes members that are involved in various cellular differentiation processes. Some proteins in this family are implicated in the regulation of platelet activation and hematopoiesis through interactions with specific ligands and activation of downstream signaling pathways such as AKT/mTOR. Other members are associated with neuroendocrine differentiation and have been shown to play a role in inhibiting adipocyte differentiation. The diverse functions of these proteins suggest their importance in developmental and physiological processes.
Phosphate transporter PHO1 (PHO1)
Type: Family

PHO1 is characterised by its role in inorganic phosphate (Pi) transport and homeostasis in plants. It is involved in various aspects of Pi handling, including sensing Pi starvation , exporting Pi out of cells , and transferring Pi between different plant tissues such as roots and shoots . It contains an SPX domain that binds inositol polyphosphate signaling molecules, which may be involved in sensing Pi levels, and an EXS domain essential for Pi efflux and proper cellular localisation. PHO1 contributes to the regulation of Pi starvation responses and may interact with transcription factors through its SPX domain . Overall, PHO1 plays a crucial role in maintaining phosphate balance within the plant, which is vital for various physiological processes including growth and stress responses.
Galactose-binding lectin (Galactose-binding_lectin)
Type: Family

This family of proteins includes galactose- and N-acetylgalactosamine-binding lectins that are implicated in cell-substratum adhesion processes. Members of this family are thought to contribute to the maintenance of cell morphology during certain stages of cell aggregation. Additionally, some proteins within this family may play a role in spore formation and could be involved in the assembly of the spore coat. The functional diversity within this family reflects a range of biological processes related to cell adhesion and development.
Diencephalon/mesencephalon homeobox (DMBX_homeobox)
Type: Family

The Diencephalon/mesencephalon homeobox protein family is characterized by its role in transcriptional repression and developmental processes in vertebrates. Members of the family are known to function as transcriptional repressors, with some forming heterodimers with OTX2 to repress OTX2-mediated transactivation on specific DNA sequences. The family is essential for brain development, with additional roles in neonatal survival, postnatal growth, and nursing ability in mammals. In zebrafish, family members are also implicated in eye and tectum development. The family belongs to the larger paired homeobox family, which is distinguished by the presence of the homeobox DNA-binding domain, a hallmark of genes that regulate developmental processes.
Leucine-rich repeat and WD repeat-containing protein 1 (LRWD1)
Type: Family

The LRWD1 family proteins are essential for the G1/S transition of the cell cycle. They recruit and stabilize the origin recognition complex (ORC) onto chromatin during G1 to establish the pre-replication complex (preRC) and to heterochromatic sites in post-replicated cells. Members of the LRWD1 family bind a combination of DNA and histone methylation repressive marks on heterochromatin, including histone H3 and H4 trimethylation marks H3K9me3, H3K27me3, and H4K20me3. This cooperative binding with DNA methylation is crucial for the silencing of major satellite repeats. The entire WD repeat region of LRWD1 proteins is necessary for these interactions, as well as for chromatin association. The family plays a significant role in maintaining the stability of ORC components ORC2, ORC3, and ORC4, which are vital for DNA replication initiation and chromatin organization.
Calcineurin B Homologous Protein 3 (CHP3)
Type: Family

The Calcineurin B Homologous Protein 3 family plays a crucial role in cellular pH regulation by modulating plasma membrane-type Na(+)/H(+) exchange activity. It is involved in hematopoietic stem cell differentiation, particularly towards the megakaryocytic lineage, and is essential for linking ERK cascade activation to the expression of ETS family genes during this process. Additionally, it participates in granulocytic differentiation in an ERK-dependent manner. Members of the family also inhibit the phosphatase activity of calcineurin and are known to bind calcium and magnesium through EF-hand domains, which induces a conformational change in the protein.
Tumor necrosis factor receptor superfamily member 10 (TNFRSF10)
Type: Family

This family of proteins includes receptors that interact with the cytotoxic ligand TNFSF10/TRAIL. Members of this family can initiate apoptosis through the formation of a death-inducing signaling complex (DISC) that activates caspase-8 and subsequent caspases. Some members contain a truncated death domain and do not induce apoptosis but may protect against it by competing for ligand binding. There is variability in the ability of these proteins to activate the NF-kappa-B pathway, with some members promoting its activation, which can be essential for certain stress-induced apoptosis pathways.
Tubulin--tyrosine ligase (Tubulin-tyrosine_ligase)
Type: Family

This family of proteins is responsible for the enzymatic activity that attaches a tyrosine residue to the C-terminal end of detyrosinated alpha-tubulin. This post-translational modification is crucial for the restoration of alpha-tubulin's tyrosine residue, which is important for the polymerization and function of microtubules. The reaction catalyzed by these enzymes plays a key role in the tubulin tyrosination/detyrosination cycle, which is implicated in various cellular processes including cell division, intracellular transport, and the maintenance of cell shape and motility.
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)
Type: Family

This family of proteins includes receptors that bind to tumor necrosis factors such as TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. Upon ligand binding, these receptors recruit the adapter molecule FADD, which in turn recruits caspase-8 to form the death-inducing signaling complex (DISC). Activation of caspase-8 initiates a cascade of caspases that leads to apoptosis. Additionally, these receptors are involved in non-apoptotic signaling pathways, including the induction of an anti-viral state and the activation of acid sphingomyelinase, contributing to various TNF-mediated effects.