SII-SWORD/CoKE huggingface dataset:
Dual Specificity Protein Phosphatases (Dual_spec_Phospatases)
Type: Family

The Dual Specificity Protein Phosphatase family is involved in the regulation of key signaling pathways through the dephosphorylation of MAP kinases such as ERK, JNK, and p38, which are critical for various cellular responses. Members of the family negatively regulate TCR signaling by inactivating the MAP3K7 adapter TAB1. Some exhibit phosphatase activity with synthetic substrates, but show limited or no activity with natural phosphoamino acids due to possible steric hindrance at the active site. Additionally, they play a role in down-regulating the cellular antiviral response by dephosphorylating activated STAT1, thereby blocking interferon-stimulated innate immune responses.
Mitochondrial Release Factor mL62 (Mito_Release_Factor_mL62)
Type: Family

The protein family is characterized by its role as peptidyl-tRNA hydrolases within the mitochondrial large ribosomal subunit. Members act as codon-independent translation release factors that have lost stop codon specificity, which may direct the termination of translation in the mitochondrion, particularly during abortive elongation. They are involved in the hydrolysis of prematurely terminated peptidyl-tRNAs, aiding in the recycling of stalled mitochondrial ribosomes. One member is noted to have a role in meiosis.
Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase (MGAT5_Glycosyltransferase)
Type: Family

This family of proteins includes glycosyltransferases involved in the modification of glycoproteins by catalyzing the addition of N-acetylglucosamine (GlcNAc) to mannose residues in N-linked oligosaccharides. These enzymes play a crucial role in the biosynthesis of branched, complex-type N-glycans, which are essential for proper protein folding, stability, and function. The activity of these proteins is important for cellular processes such as signaling pathway activation, actin cytoskeleton reorganization, cell-cell adhesion, cell migration, and the inflammatory response. They are also involved in modulating the interactions between growth factors and their receptors, affecting processes like angiogenesis and leukocyte evasion. Additionally, they contribute to the regulation of integrin and laminin-mediated neuronal cell adhesion and migration.
PINc/VapC ribonuclease toxin-antitoxin (PINc/VapC_TA)
Type: Family

The PINc/VapC protein family comprises ribonucleases that function as toxic components of type II toxin-antitoxin (TA) systems. Members of the family are RNases that play a role in bacterial stress response and persistence by inhibiting growth through the degradation of RNA. Each VapC toxin is paired with a cognate VapB antitoxin that neutralizes its activity. The interaction between VapC toxins and VapB antitoxins is crucial for the regulation of the TA system, which can be involved in various cellular processes including the response to environmental stressors.
HEAT Repeat-containing Protein 6 (HEAT6)
Type: Family

The HEAT repeat-containing protein 6 family is characterized by the presence of HEAT repeats, which are tandemly repeated units typically involved in intracellular transport processes and protein-protein interactions. Members of this family are found across various species, indicating a conserved functional role. The human variant is noted as an amplification-dependent oncogene, suggesting a potential involvement in cancer progression through mechanisms that may include altered cell signaling or chromosomal stability. The exact functions in other species are not specified, but the conservation of the HEAT repeats implies a fundamental role in cellular machinery.
Multiple EGF-like domains/Integrin beta-like (MEGF/SIB)
Type: Family

The MEGF/SIB family is involved in various cellular functions, including cellular adhesion, phagocytosis, and neuron spacing in the retina. Members of the family act as membrane receptors for the engulfment of apoptotic cells, interacting with signals like C1q and phosphatidylserine. They are implicated in the formation of vacuoles and may uptake amyloid-beta peptides. Essential in myogenesis, they regulate the balance between proliferation and differentiation of muscle satellite cells via the notch signaling pathway. Additionally, they contribute to the even distribution of neuron subtypes across the retina, ensuring uniform visual field processing.
Serine/Arginine Repetitive Matrix Domain-Containing Protein (SRRM_Domain-Containing)
Type: Family

This family of proteins includes splicing factors that are involved in pre-mRNA processing and neural cell differentiation. Members of this family are known to regulate alternative splicing events, which are critical for the expression of neural-specific isoforms and the proper functioning of the nervous system. Some proteins within this family may also play a role in cancer progression by modulating cell invasiveness. The family is characterized by the presence of serine/arginine repetitive matrix domains, which are indicative of their involvement in RNA binding and splicing regulation.
Multiple coagulation factor deficiency protein 2-like (MCFD2-like)
Type: Family

The protein family is involved in various cellular processes, including the ER-to-Golgi transport of selected proteins and cell-cell adhesion. Members of the family, mainly from animals, form a specific cargo receptor complex, known as the MCFD2-LMAN1 complex, which is essential for the secretion of coagulation factors . Additionally, some family members mediate cell-cell adhesion in a calcium-dependent manner and can inhibit cell growth in several cell lines . The presence of EF-hand domains suggests that calcium ions are crucial for the structural folding and function of these proteins.

This entry also includes Lymphotoxin beta receptor inhibitor, which Inhibits multimerisation of lymphotoxin-beta receptor (LTBR) and downstream NF-kappa-B signalling activation , and Longistatin, an anticoagulant and fibrinolytic protease that modulates blood feeding of ticks on vertebrate hosts .
Spermatogenesis and Ciliary Microtubule-associated Protein (Spermatogenesis_Ciliary_MAP)
Type: Family

This family of proteins is associated with spermatogenesis and ciliary function. Members are involved in apoptosis regulation and microtubule dynamics. They play a role in microtubule stabilization, bundling, and protection against depolymerization, which is crucial for cell migration, ciliary structure integrity, and function. These proteins also interact with actin, contributing to cytoskeletal organization and cell motility. They are essential for the survival of certain cell types and are implicated in the planar cell polarity signaling pathway, which is important for the asymmetric distribution of microtubules in ciliated epithelia.
EGFR Signaling Regulator Kinase (EGFR_SigReg_Kinase)
Type: Family

The protein family includes non-receptor tyrosine-protein and serine/threonine-protein kinases involved in cell signaling, particularly in relation to EGFR. The family members are implicated in various cellular processes such as cell spreading, migration, survival, growth, and proliferation. They act as downstream effectors of CDC42, mediating cell migration and influencing synaptic function and brain development. The kinases phosphorylate a range of substrates, including AKT1, AR, and WWOX, playing roles in endocytosis, ubiquitination, and tumor growth regulation. Additionally, the family encompasses negative regulators of EGFR signaling, which inhibit EGFR catalytic activity and autophosphorylation, affecting keratinocyte proliferation, differentiation, and responses to steroid hormones.
FYVE-type Zinc Finger Domain-Containing Protein (FYVE-type_Zinc_Finger)
Type: Family

This family of proteins is involved in cellular processes related to adhesion and motility. Members of this family play a role in the dynamic assembly and disassembly of focal adhesions, which are critical for cell movement. They regulate the dephosphorylation of PTK2/FAK1, a key event in focal adhesion turnover, and influence the cell surface expression of integrin beta-1. Additionally, these proteins contain a FYVE-type zinc finger domain that mediates interactions with PTK2/FAK1 and PI(3)P, leading to association with endosomes. The C-terminal region of these proteins is structurally similar to pleckstrin homology (PH) domains but lacks the typical interface for binding phosphatidylinositol phosphate.
ER-associated autophagy and membrane dynamics regulator (ER_autophagy_membrane_reg)
Type: Family

This family of proteins includes autophagy regulators and endoplasmic reticulum (ER) shaping proteins. Members are involved in the regulation of ER-associated degradation pathways, particularly under stress conditions, where they facilitate ER fragmentation and delivery into lysosomes. They interact with ATG8 family proteins to mediate this process. Additionally, some members are implicated in the modulation of glutamate transport by altering the affinity and catalytic efficiency of specific transporters. They also play a role in the formation and stabilization of ER tubules and may negatively regulate apoptosis by affecting caspase activity. Furthermore, these proteins are suggested to be involved in various cellular processes including protein transport, membrane trafficking, and cell signaling during hematopoietic maturation.
Nuclear exosome targeting complex subunit ZCCHC8 (NEXT_complex_subunit_ZCCHC8)
Type: Family

The ZCCHC8 family is involved in the regulation of RNA stability and processing within the nucleus. Members of this family serve as scaffolding subunits of the trimeric nuclear exosome targeting (NEXT) complex, which plays a critical role in the surveillance and degradation of aberrant transcripts and non-coding RNAs. The NEXT complex acts as an RNA exosome cofactor, directing certain non-coding, short-lived RNAs towards exosomal degradation. Additionally, the ZCCHC8 family is implicated in pre-mRNA splicing and is essential for the 3'-end maturation of the telomerase RNA component (TERC). This maturation process is crucial for the proper targeting of TERC to the nuclear RNA exosome and for maintaining telomerase function, which is vital for chromosome integrity and cellular longevity.
Centrosome and Cilium Assembly Protein (Centro_Cilium_Assembly)
Type: Family

This family of proteins is involved in centrosome and cilium assembly and function. Members of this family are known to be components of the centrosome, specifically associated with centrioles. They play a crucial role in centrosome cohesion by forming a fiber-like linker between centrioles. Additionally, some family members are involved in the initiation of primary cilium assembly as part of the distal appendage region of the centriole. They may also cooperate with other proteins, such as IFT20, to facilitate the trafficking of ciliary membrane proteins from the Golgi complex to the cilium, which is essential for ciliary assembly and function.
CRISPR-associated Cas10/Csm1 subtype III-A protein (Cas10/Csm1_subtype-III-A)
Type: Family

This family of proteins is involved in the CRISPR adaptive immune system, which defends against mobile genetic elements like viruses and plasmids. Members possess a single-strand-specific deoxyribonuclease (ssDNase) activity that digests ssDNA with both exo- and endonuclease actions. They are part of the type III-A Csm effector complex, which also includes CRISPR RNA (crRNA) and target ssRNA. The complex binds crRNA and acts as a crRNA-guided RNase, DNase, and cyclic oligoadenylate synthase. Binding of target RNA to the crRNA is essential for these activities. The proteins synthesize cyclic oligoadenylates (cOAs) from ATP, which act as second messengers to stimulate ssRNase activity and induce an antiviral state. The N-terminal HD domain is responsible for ssDNase activity, while the C-terminal GGDEF domain synthesizes cOAs. ssDNase activity is regulated by target RNA binding and is inhibited by EDTA.
Rho GTPase-activating regulator (Rho-GAP_regulator)
Type: Family

This family of proteins includes Rho GTPase-activating proteins (GAPs) that function as regulators of Rho-type GTPases, converting them from an active GTP-bound state to an inactive GDP-bound state. They play a crucial role in cytoskeletal remodeling by controlling the activity of Rho GTPases such as RHOA, CDC42, and RAC1. Members of this family are involved in various cellular processes, including placental development, trophoblast cell migration, presynaptic development, axon polarity acquisition, and synaptic component localization. They act downstream of specific signaling pathways and are essential for the regulation of movement, egg-laying, and maintaining high levels of synaptic proteins in active zones.
Elongin BC-PRC2 Interaction & Viral Restriction (ElonginBC-PRC2_ViralRestrict)
Type: Family

The protein family includes scaffold proteins that bridge the PRC2/EZH2 complex with the elongin BC complex, regulating transcriptional status of PcG target genes in ESCs. They maintain low expression levels at PcG targets by recruiting elongin BC, limiting PRC2/EZH2 activity. They also interact with USP7, leading to H2B deubiquitination at promoters, and play a role in neuronal differentiation. Other members inhibit CAPN3 protease activity and are involved in SMC5-SMC6 complex recruitment for viral restriction and PML nuclear body localization. Additionally, they form a complex with SLF2 for SMC5-SMC6 recruitment to viral replication sites. The family also includes proteins belonging to the DACH/dachshund family, suggesting a diversity of functions.
Fibronectin type III domain-containing protein 4/5 (FNDC_type_III_4/5)
Type: Family

This family of proteins includes fibronectin type III domain-containing protein 4 and 5 (FNDC4/5).

FDNC4 is involved in anti-inflammatory processes, particularly in the gastrointestinal tract. It interacts with macrophages to reduce the expression of pro-inflammatory genes and modulate macrophage functions such as phagocytosis, largely through STAT3 activation and signaling pathways . These proteins play a role in controlling the immune response during inflammatory conditions like colitis.

FDNC5 is a type I membrane protein that is cleaved to produce irisin, a hormone-like molecule that is secreted from skeletal muscle into the extracellular milieu and circulation. Physical activity induces irisin production, and irisin mediates the beneficial effects of physical activity in adipose tissue, brain, and bone . In mouse, it is implicated in the physiological changes associated with muscular exercise, including the induction of browning in white adipose tissue through the upregulation of UCP1 expression, potentially involving the nuclear receptor PPARA. However, the role of these proteins in exercise-induced benefits and adipose tissue browning may vary between species, as in humans may not be involved in the beneficial effects of muscular exercise, nor in the induction of browning of human white adipose tissue .
F-box Protein Family Substrate Recognition Components (F-box_SCF_Substrate_Recog)
Type: Family

The F-box protein family is involved in the regulation of protein degradation via the ubiquitin-proteasome system. Members of this family function as substrate-recognition components of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complexes. They are responsible for the ubiquitination of specific target proteins, marking them for proteasomal degradation. This process is crucial for various cellular functions, including cell cycle progression, signal transduction, and inflammatory responses. Some family members also interact with kinases and other proteins to modulate processes like p53/TP53-dependent transactivation and histone modification, impacting cell proliferation and gene expression regulation.
Intracellular Trafficking and Signaling Regulator (Intracell_Traff_Signaling_Reg)
Type: Family

This family of proteins is involved in intracellular trafficking and the organization of membrane receptors. Members are known to interact with cytohesins, influencing ARF protein activation and potentially sequestering cytohesins in the cytoplasm to regulate their function. Some family members are implicated in synaptic processes, specifically in the organization of metabotropic glutamate receptors, which are critical for synaptic signaling. Others play a role in meiotic events, such as chromosome pairing and DNA repair during prophase I, and may also limit chromosome movement in a dynein-dependent manner. The diverse functions suggest a broad role in cellular organization and signaling.
Non-receptor Tyrosine Phosphatase (Non-rcpt_Tyr_Phosphatase)
Type: Family

This family of proteins includes non-receptor tyrosine phosphatases that play a role in modulating signaling pathways initiated by tyrosine phosphorylated cell surface receptors. They are involved in various cellular processes such as hematopoiesis, development, and cell fate determination. Members of this family contain SH2 domains that can function as auto-inhibitory domains or mediate interactions with other proteins, influencing the phosphatase activity. They are implicated in the regulation of oocyte maturation, neuromuscular junction formation, fluid homeostasis, vulva induction, and the inhibition of dauer formation. Some members are also involved in the negative regulation of mast cell activation and the induction of gene expression in response to specific stimuli.
Rab9 effector with kelch motifs (Rab9_kelch_effector)
Type: Family

This family of proteins serves as effectors for the Rab9 GTPase, playing a crucial role in the transport process from endosomes to the trans-Golgi network (TGN). The members of this family are characterized by the presence of kelch motifs, which are typically involved in protein-protein interactions. Through these interactions, the proteins facilitate the tethering and fusion of transport vesicles with their target membranes, thereby ensuring the proper delivery of cargo proteins and lipids to the TGN. This function is essential for maintaining the integrity of the intracellular trafficking pathway and the overall cellular homeostasis.
Kelch domain-containing protein 10 (KLHDC10)
Type: Family

This family of proteins functions as substrate-recognition components of a Cul2-RING E3 ubiquitin-protein ligase complex, which is involved in the DesCEND pathway. They recognize specific C-terminal degrons in target proteins, leading to ubiquitination and subsequent degradation. These proteins are known to specifically bind to C-terminal proline-glycine or alanine motifs. They play a role in the ribosome-associated quality control pathway by mediating the extraction of nascent chains from stalled ribosomes and targeting them for degradation. Additionally, they are implicated in oxidative stress-induced cell death by activating specific kinases and inhibiting phosphatase activity on these kinases. They also regulate necroptosis, a form of programmed cell death.
Spindle_Organization_and_Thrombomodulin (Spindle_Org/Thrombomodulin)
Type: Family

This family of proteins includes structural components that stabilize and organize microtubule spindles during cell division, such as mitosis in embryonic somatic cells and meiosis in spermatocytes. Their function is influenced by the Ran pathway. Additionally, members of this family serve as specific endothelial cell receptors that form complexes with thrombin, playing a crucial role in the coagulation cascade by converting protein C to its activated form, which in turn regulates the activity of coagulation factors Va and VIIIa, ultimately reducing thrombin generation.
STE12 transcription factor (STE12_transcription_factor)
Type: Family

The STE12 transcription factor family comprises proteins involved in various aspects of fungal development and stress response. Members of this family typically function as transcription factors that bind to specific DNA sequences to regulate gene expression. They play crucial roles in sexual reproduction, mating processes, and the formation of specialized structures like pseudohyphae and hyphae. Some family members are involved in the response to environmental stresses such as weak acid stress, and may also regulate genes involved in infectious hyphae growth. The family is characterized by a DNA-binding domain that can influence cellular differentiation and developmental pathways, including the potential regulation of a sexual phase in certain species.
Oxidoreductase NAD-binding domain-containing protein (Oxidoreductase_NAD-binding)
Type: Family

This family of proteins includes oxidoreductases that contain a domain for binding NAD, a coenzyme involved in redox reactions. These proteins are likely involved in various metabolic processes, where they catalyze the oxidation-reduction reactions of different substrates, transferring electrons from one molecule to another. The NAD-binding domain is critical for the enzyme's activity, providing a site for the coenzyme to interact with the protein and participate in the catalytic cycle. The specific functions and substrates of these oxidoreductases may vary across different organisms and tissues, reflecting their diverse roles in cellular metabolism.
Spermadhesin-Link domain-containing protein (Spermadhesin-Link_domain)
Type: Family

This family of proteins includes members that are involved in various biological processes related to reproduction, cell division, and extracellular matrix organization. Some proteins in this family function as growth factors, stimulating cell division and hormone secretion in reproductive tissues. Others mediate the binding of sperm to the egg's zona pellucida, which is crucial for fertilization. Additionally, certain members are key regulators of extracellular matrix remodeling, with activities such as catalyzing the transfer of heavy chains to hyaluronan, modulating chemokine interactions, and influencing leukocyte migration. These proteins also play roles in tissue remodeling, osteogenesis, and bone protection during inflammation.
AEBP2/jing C2H2-type zinc-finger (AEBP2/jing_C2H2-ZnF)
Type: Family

The AEBP2/jing C2H2-type zinc-finger family includes proteins that play roles in transcriptional regulation, often through interaction with chromatin-modifying complexes. Members of the family are known to function as accessory subunits for the Polycomb repressive complex 2 (PRC2), contributing to the trimethylation of histone H3K27 (H3K27me3) and subsequent transcriptional repression. They are involved in nucleosome localization of PRC2, affecting gene expression patterns during development and cellular differentiation. Some family members are also implicated in DNA-binding and transcriptional repression, potentially interacting with and stimulating histone methyltransferase complexes. In Drosophila, the jing homolog is involved in various developmental processes, including CNS axon development, tracheal tubule development, and regenerative growth, by interacting with Polycomb and trithorax group proteins.
ATRX domain-containing protein (ATRX_domain-containing)
Type: Family

This family of proteins is involved in transcriptional regulation and chromatin remodeling. They are key players in DNA replication across various cellular contexts, with a specific role in the replication of certain genomic regions. These proteins bind to DNA tandem repeats found in telomeres and euchromatin, as well as to DNA quadruplex structures. They are implicated in the stabilization of G-rich regions by remodeling G4 DNA and incorporating histone variant H3.3 into nucleosomes. As catalytic components of the ATRX:DAXX chromatin remodeling complex, they exhibit ATP-dependent DNA translocase activity, facilitating the replication-independent deposition of histone H3.3 at specific chromosomal locations. Their function in heterochromatin targeting likely involves reading the methylation states of histone H3 and interacting with other chromatin-associated proteins. They also participate in the regulation of allele-specific gene expression and may play roles in brain development and facial morphogenesis. Additionally, they form complexes with other proteins to regulate histone modification levels at specific gene loci, particularly those coding for zinc-finger proteins.