SII-SWORD/CoKE huggingface dataset:
VLCFA Elongation and Steroid Dehydrogenase (VLCFA-Steroid_DH)
Type: Family

The protein family includes enzymes that catalyze key reactions in lipid metabolism and steroid hormone biosynthesis. Members are involved in the elongation cycle of long-chain fatty acids, adding two carbons to produce very long-chain fatty acids (VLCFAs), which are precursors for membrane lipids and lipid mediators. Some family members also function in the conversion of 17-oxosteroids to 17beta-hydroxysteroids, playing a crucial role in the biosynthesis of androgens like testosterone. Additionally, certain enzymes within the family contribute to bile acid metabolism in the human gut microbiota by converting 7-oxo-lithocholate to ursodeoxycholate, a secondary bile acid with chemopreventive properties.
Aldehyde dehydrogenase-related metabolic enzymes (ALDH-related_metabolic_enz)
Type: Family

This family of proteins includes various aldehyde dehydrogenases with diverse functions. Members are involved in metabolic pathways such as the degradation of D-sulfoquinovose, generating sulfolactate, and the utilization of taurine as a nitrogen source. Some enzymes in this family are responsible for the NAD(P)-dependent oxidation of glyceraldehyde-3-phosphate to 3-phosphoglycerate, playing a role in generating NADPH for biosynthetic reactions. Others are implicated in F420 biosynthesis by oxidizing lactaldehyde to lactate. Additionally, certain members may participate in phosphonate degradation. The enzymes exhibit substrate specificity and are regulated by various metabolites, indicating their adaptation to specific cellular roles.
Mitochondrial serine/threonine phosphatase (Mito_Ser/Thr_phosphatase)
Type: Family

This family of proteins exhibits serine/threonine phosphatase activity, with members involved in the dephosphorylation and activation of specific kinases such as Pk92B and MAP3K5. Despite being classified within the phosphoglycerate mutase family, these proteins do not display phosphoglycerate mutase activity. They are implicated in the regulation of mitochondrial dynamics and may act as central mediators for programmed necrosis. Some family members are substrates for KEAP1-dependent ubiquitin ligase complexes and contribute to the repression of NFE2L2-dependent gene expression. They are targeted to the cytosolic side of the outer mitochondrial membrane by a non-cleaved mitochondrial targeting sequence located at the N-terminus, which includes a potential transmembrane alpha-helix.
Notch Signaling and Cell Fate Determination (Notch_Cell-Fate_Det)
Type: Family

The protein family is involved in cell fate determination, differentiation, proliferation, and apoptotic programs through Notch signaling. Members function as receptors for ligands such as Jagged and Delta proteins, influencing various developmental processes including cardiovascular development, hematopoiesis, neurogenesis, and angiogenesis. They also play roles in maintaining stem cell populations, regulating immune system development, and contributing to tissue morphogenesis and integrity. Some members regulate adipogenesis, while others are involved in maintaining the structure and function of photoreceptor cells or the extracellular matrix.
Protein Phosphatase 2A Regulatory Subunit A (PP2A_Regulatory_Subunit_A)
Type: Family

This family of proteins functions as scaffolding molecules that coordinate the assembly of a catalytic subunit with a variable regulatory B subunit, forming part of protein phosphatase 2A (PP2A). They are involved in various cellular processes including chromosome segregation, microtubule dynamics, cell cycle progression, and signal transduction pathways. These proteins play roles in dephosphorylating key components such as TAU/MAPT and AKT1, impacting neuronal function and T-cell homeostasis. Additionally, they are implicated in plant development and innate immunity, with some members acting as positive or negative regulators of PP2A catalytic activity.
GlcNAc and Chitin Interaction and Degradation (GlcNAc_Chitin_IntDeg)
Type: Family

The GbpA family includes proteins with diverse functions related to chitin interaction and degradation, as well as viral protection and cellular attachment. Members of the family are involved in binding to GlcNAc residues and promoting attachment to epithelial cell surfaces, chitin, and zooplankton, enhancing bacterial colonization in various environments. Some proteins in the family are key components of virus occlusion bodies, protecting the virus in harsh conditions. Others are involved in the oxidative cleavage of glycosidic bonds in chitin or cellulose via a copper-dependent mechanism, contributing to the degradation of lignocellulosic biomass or chitin as a carbon source. The family also includes proteins that bind chitin without hydrolyzing it, suggesting a role in non-catalytic chitin interaction.
Rho GTPase-activating (RhoGAP)
Type: Family

The Rho GTPase-activating protein (RhoGAP) family is involved in the regulation of the Rho-type GTPases, which are critical for actin cytoskeleton dynamics, cell morphology, polarity, and motility. Family members act as GTPase activators by converting active GTP-bound Rho GTPases to their inactive GDP-bound state. Some proteins within the family have domains that can exert an autoinhibitory effect on RhoGAP activity, such as the BAR domain. These proteins play roles in various cellular processes including endothelial cell tubulogenesis, angiogenesis, and the negative regulation of cell spreading. They may also interact with other proteins, such as FLNA, to localize to specific cellular structures and influence cell signaling pathways. The family's activity is essential for maintaining proper cellular function and structure across a range of organisms from yeast to humans.
Phosphatidylinositol/phosphatidylcholine transfer (PI/PC_transfer)
Type: Family

This family of proteins is involved in the intracellular transport of secretory proteins, particularly from the Golgi complex. Members of this family have the ability to catalyze the transfer of phosphatidylinositol and phosphatidylcholine between different membranes in vitro. Some proteins within this family also play a role in the synthesis and organization of phosphatidylinositol 4,5-bisphosphate in cellular membranes, which is crucial for processes such as root hair tip elongation and polarized membrane trafficking in plants. Additionally, certain members are essential for viability and secretion, and are involved in the regulation of specific trans-Golgi export pathways, including the trafficking and localization of lipid raft proteins to the plasma membrane.
Basic leucine zipper (bZIP) transcription factors (bZIP_transcription_factors)
Type: Family

The bZIP family of transcription factors is characterized by the basic leucine zipper domain which facilitates DNA binding and dimerization. Members of this family are involved in a wide range of biological processes, including transcriptional regulation of genes associated with anti-apoptosis, cell growth, DNA damage response, innate immunity, oxidative stress responses, and developmental processes. They bind to specific DNA sequences such as the cAMP response element (CRE) or activator protein 1 (AP-1) consensus sequences to activate or repress transcription. Some family members also interact with histone acetyltransferases or methyltransferases, influencing chromatin structure and gene expression. The activity of these proteins can be modulated by phosphorylation, impacting processes like the DNA damage response and cell death. The bZIP proteins play roles in cellular stress responses, secondary metabolism, and can have oncogenic or tumor suppressor activities depending on the context.
Mitochondrial Solute Carrier (Mito_Solute_Carrier)
Type: Family

This family of proteins includes mitochondrial carriers that facilitate the transport of solutes, metabolites, nucleotides, and cofactors across the mitochondrial inner membrane. They play a crucial role in various metabolic processes, including the malate-aspartate shuttle, which is essential for transferring reducing equivalents across the mitochondrial membrane. Members of this family are involved in the electrogenic antiport of aspartate and glutamate, which is important for amino acid metabolism and energy production. Some family members are also capable of calcium-dependent binding and transport, which influences the carrier's activity and substrate specificity. The regulation of these transporters can involve calcium binding, which modulates the interaction between the N-terminal regulatory domain and the C-terminal carrier domain, affecting substrate translocation.
mRNA Capping Enzyme and RNA Phosphatase (mRNA_Capping_Enz/RNA_Phosphat)
Type: Family

The protein family is involved in mRNA metabolism, particularly in the capping process which is essential for mRNA stability and translation. Members of the family exhibit bifunctional enzymatic activities: RNA 5'-triphosphatase activity, which removes the gamma-phosphate from the 5'-triphosphate end of nascent mRNA, and mRNA guanylyltransferase activity, which transfers the GMP moiety of GTP to the 5'-diphosphate terminus of RNA via a covalent enzyme-GMP intermediate. Some members also display RNA 5'-diphosphatase activity and can bind to RNA. Additionally, certain proteins in the family have been noted to possess phosphatase activity with various substrates such as ATP, ADP, and O-methylfluorescein phosphate in vitro. The family includes proteins that may play roles in nuclear mRNA metabolism and the regulation and processing of viral mRNAs.
Vitamin B12-binding component of ABC transporter (Vitamin_B12-ABC_binding)
Type: Family

This family of proteins is involved in the transport of vitamin B12 across cellular membranes. They are components of the ATP-binding cassette (ABC) transporter complex BtuCDF, which is responsible for the import of vitamin B12. Members of this family specifically bind vitamin B12 and are responsible for delivering it to the periplasmic surface of the BtuC component of the transporter complex.
RING-box E3 Ubiquitin Ligase (RING-box_E3_Ubiquitin_Ligase)
Type: Family

The RING-box family is involved in the regulation of protein degradation via the ubiquitin-proteasome system. Members of this family are components of E3 ubiquitin ligase complexes, such as SCF (SKP1-CUL1-F-box protein) and APC/C (Anaphase-promoting complex/cyclosome), which mediate the ubiquitination of target proteins, marking them for proteasomal degradation. This process is crucial for various cellular functions including cell cycle progression, signal transduction, transcription, and DNA repair. The RING-type zinc finger domain within these proteins is essential for their ubiquitin ligase activity, coordinating an additional zinc ion and recruiting E2 ubiquitination enzymes to facilitate the transfer of ubiquitin to substrates. The family's activity is also involved in neddylation of cullins and may play a role in protecting cells from apoptosis.
AP2/ERF transcription factor, ERF subfamily (AP2/ERF_TF_ERF_subfamily)
Type: Family

The AP2/ERF transcription factor family, specifically the ERF subfamily, is involved in the regulation of gene expression in response to various stress factors and components of stress signal transduction pathways. Members of this family typically act as transcriptional activators and are characterized by their ability to bind to the GCC-box pathogenesis-related promoter element. Their role is crucial in plant development and stress tolerance, including responses to abiotic stresses such as dehydration, salt, and osmotic stress. The ERF subfamily contributes to the complex network of gene regulation under stress conditions, potentially influencing the expression of stress-related genes and facilitating adaptive responses.
SH3 domain-binding glutamic acid-rich protein (SH3BGR)
Type: Family

This family of proteins appears to be involved in various cellular processes, including acting as adapter proteins that may bridge other proteins or proteins with mRNAs, potentially influencing the expression of specific mRNAs. Some members are suggested to function as ubiquitin ligase-substrate adapters, which could tag proteins for degradation. There is also an association with translating cytoplasmic ribosomes, indicating a possible role in protein synthesis. Additionally, certain members might modulate glutaredoxin activity, which is important for redox homeostasis, and may be involved in cytoskeleton organization, impacting cell structure and dynamics. The presence of an SH3-binding motif, although buried within the tertiary structure, suggests a potential for protein interaction, although its direct role in binding is unclear.
Mitochondrial Enoyl-ACP Reductase (Mito_Enoyl-ACP_Reductase)
Type: Family

The mitochondrial enoyl-[acyl-carrier-protein] reductase family is involved in the NADPH-dependent reduction of trans-2-enoyl thioesters as part of mitochondrial fatty acid synthesis type II. Members of this family utilize acyl carrier protein (ACP) as an acyl group carrier, although they can also accept CoA thioesters as substrates in vitro. The family plays a crucial role in fatty acid chain elongation within mitochondria, which is essential for respiration and the maintenance of the mitochondrial compartment. Some members display substrate specificity, showing a preference for medium-chain substrates and may contribute to lipoic acid biosynthesis, which is important for protein lipoylation and mitochondrial respiratory activity, particularly in certain cell types like Purkinje cells.
Mitochondrial inheritance protein 9 (Mito_inheritance_9)
Type: Family

This family of proteins is involved in the inheritance and distribution of mitochondria, which are essential organelles responsible for energy production in eukaryotic cells. Members of this family may play a role in ensuring proper mitochondrial segregation during cell division, thereby influencing mitochondrial biogenesis and dynamics. The precise molecular mechanisms by which these proteins function, as well as their interactions with other mitochondrial or cellular components, remain to be fully elucidated. However, their conservation across various yeast species suggests a fundamental role in mitochondrial inheritance.
Sialic acid-binding Ig-like lectin (SIGLEC)
Type: Family

The SIGLEC family proteins are sialic acid-binding Ig-like lectins involved in cell-cell adhesion, immune regulation, and maintenance of immune cells in a resting state. They recognize and bind to sialic acid-bearing glycans, mediating interactions with a preference for alpha-2,3- or alpha-2,6-linked sialic acid. SIGLEC family members contain immunoreceptor tyrosine-based inhibitor motifs (ITIMs) in their cytoplasmic domains, which upon phosphorylation, recruit SH2-containing phosphatases to modulate cellular responses. They play roles in inhibiting signal transduction, regulating B-cell antigen receptor signaling, controlling autoimmunity, and protecting neurons against apoptosis. Some SIGLEC proteins are involved in the negative regulation of neurite outgrowth and may act as inhibitory receptors in the immune response.
RNA Polymerase II Transcription Factor IWS1 (RNAPII_TF_IWS1)
Type: Family

The IWS1 family comprises transcription factors that play crucial roles in RNA polymerase II (RNAPII) transcription regulation. Members of the IWS1 family are involved in various stages of the transcription process, including post-recruitment and recruitment of SPT15/TBP. They are key in defining the composition of the RNAPII elongation complex and modulating the production of mature mRNA transcripts. The IWS1 family proteins act as assembly factors, recruiting multiple components to the RNAPII elongation complex. They bind to the transcription elongation factor SUPT6H associated with the C-terminal domain (CTD) of POLR2A, facilitating the recruitment of mRNA export factors and histone modifying enzymes. This ensures proper mRNA splicing, efficient mRNA export, and elongation-coupled H3K36 methylation, a hallmark of active transcription.
RMT2/GAMT Methyltransferase (RMT2/GAMT_Mtase)
Type: Family

The RMT2 methyltransferase family comprises enzymes that utilize S-adenosyl-L-methionine (SAM) to methylate arginine residues in target proteins, forming N5-methylarginine. This modification plays a critical role in the regulation of protein function and RNA processing. Members of this family are also involved in the conversion of guanidinoacetate to creatine, a process essential for energy storage in muscle and nerve tissues. The family is part of the class I-like SAM-binding methyltransferase superfamily, indicating a shared mechanism for SAM-dependent methylation across diverse biological contexts.
Cytochrome c oxidase-assembly factor COX23 (COX23)
Type: Family

The COX23 family consists of mitochondrial proteins that are essential for the assembly of cytochrome c oxidase, a key component of the mitochondrial respiratory chain responsible for the final step of the electron transport process. Members of the COX23 family play a crucial role in the proper functioning of the respiratory chain by ensuring the correct assembly of cytochrome c oxidase, thereby facilitating efficient energy production within the cell.
FMRFamide-related neuropeptide (FMRFamide-related_np)
Type: Family

This family of proteins includes neuropeptides that modulate various physiological processes. Members are involved in the modulation of muscle contraction in both somatic and visceral muscles, including the heart. They act as excitatory neurotransmitters at neuromuscular junctions and have roles in the regulation of cardiovascular function. In some species, they influence chromatophore expansion, affecting color changes. These peptides also participate in the regulation of behaviors such as locomotion, feeding, and stress responses. They bind to G-protein coupled receptors, including npr-1 and npr-22, to exert their effects. Some peptides in this family are implicated in the modulation of neural activity, either exciting or inhibiting neurons. They are also involved in the regulation of fat metabolism and energy homeostasis, as well as reproductive functions such as sperm navigation.
Mammalian Reproductive Hormone Insulin-like (Repro_Hormone_Insulin-like)
Type: Family

The protein family in question is involved in various reproductive and developmental processes in mammals. Members of the family function as hormones, such as relaxin, which works with estrogen to dilate the birth canal during childbirth, and may also play a role in the remodeling of connective tissues during pregnancy. This includes promoting the growth of pubic ligaments and the ripening of the cervix. Other members, like insulin-like peptide INSL6, are implicated in sperm development and fertilization. Additionally, some proteins within the family may be important in trophoblast development and bone formation regulation. All members share a structural similarity, belonging to the insulin family, which suggests a common evolutionary origin and potentially similar biochemical mechanisms.
Sulfatase Modifying Factor and Kinase (Sulfatase_Mod_Factor_Kinase)
Type: Family

The protein family is involved in various biological processes, including the post-translational modification of sulfatases and the biosynthesis of ergothioneine, an antioxidant that protects bacteria from oxidative stress. Some family members are inactive enzymes that inhibit sulfatase activation, while others are active oxidases catalyzing the formation of formylglycine, a key step in activating sulfatases. Additionally, the family includes serine/threonine-protein kinases that may interact with host proteins during intracellular growth and a chaperone protein necessary for the proper folding of secreted enzymes. Hercynine oxygenases within the family catalyze the oxidative sulfurization of hercynine in ergothioneine biosynthesis, contributing to bacterial virulence and protection against redox stress.
Monoacylglycerol and Diacylglycerol Lipase (MAG_DAG_Lipase)
Type: Family

The protein family is involved in the hydrolysis of various lipid substrates, including monoacylglycerides and diacylglycerides, to free fatty acids and glycerol. Members of the family contribute to diverse biological processes such as endocannabinoid signaling, nociperception, pain perception, cancer cell migration, invasion, tumor growth, and the detoxification of xenobiotics. Some proteins within the family are implicated in the biosynthesis of antibiotics and lignin, as well as the regulation of inflammatory responses and apoptosis in host cells. The family includes enzymes with esterase and lipase activities, showing preferences for substrates with specific chain lengths and types of fatty acids. Inhibition profiles vary among family members, with some being inhibited by serine esterase inhibitors and others not affected by certain detergents.
TonB-dependent transporter energy transducer (TonB-dependent_transducer)
Type: Family

This family of proteins interacts with outer membrane receptor proteins to facilitate the high-affinity binding and energy-dependent uptake of specific substrates into the periplasmic space. Members of this family are involved in the transduction of energy from the cytoplasmic membrane to outer membrane processes that require energy, such as the active transport of ligands. These proteins are essential for the utilization of various nutrients and are also implicated in the infection processes of certain bacteriophages and in bacterial virulence.
MurCDEF Family: Cell Wall and Coenzyme F430 Synthesis (MurCDEF_CellWall_CoF430Synth)
Type: Family

The MurCDEF family is involved in essential biological processes, including cell wall formation and methanogenesis. Members of the MurF subfamily, such as UDP-N-acetylmuramoyl-tripeptide--D-alanyl-D-alanine ligases, catalyze the final step in the synthesis of UDP-N-acetylmuramoyl-pentapeptide, a precursor of murein, which is crucial for bacterial cell wall integrity. These enzymes add D-alanyl-D-alanine to UDP-MurNAc-L-alanyl-gamma-D-glutamyl-L-lysine, and some can also utilize UDP-MurNAc-tripeptide containing mesodiaminopimelic acid. Additionally, MurF enzymes can influence the expression of antibiotic resistance and may play a role in cell division control. Another member, Coenzyme F(430) synthetase, is involved in the biosynthesis of coenzyme F430, a nickel-containing tetrapyrrole that is the prosthetic group of methyl-coenzyme M reductase, central to methanogenesis and anaerobic methane oxidation. This enzyme activates the g-propionate side chain of seco-F430 for intramolecular C-C bond formation, creating the carbocyclic F ring of coenzyme F430.
Acyl-CoA Carboxylase Beta Subunit (AccD/PCCB)
Type: Family

The AccD/PCCB family comprises enzymes involved in fatty acid and amino acid metabolism. Members of this family function as carboxyltransferases, which are part of larger enzyme complexes that catalyze the carboxylation of various CoA ester substrates. These enzymes are biotin-dependent and play a role in the catabolism of odd chain fatty acids and branched-chain amino acids such as isoleucine, threonine, methionine, and valine. The carboxylation reaction is crucial for the conversion of propionyl-CoA to methylmalonyl-CoA, a step in the metabolic pathway that leads to the generation of energy and synthesis of important biomolecules. Some family members are also involved in the formation of electrochemical gradients across membranes, which are used for ATP synthesis. The beta subunits typically contain a carboxyl transferase domain that transfers the carboxyl group from carboxylated biotin to the substrate. The family includes enzymes from a variety of organisms, indicating a conserved role in central metabolic processes.