SII-SWORD/CoKE huggingface dataset:
26S Proteasome Regulatory ATPase (26S_Proteasome_ATPase)
Type: Family

This family of proteins is involved in the ATP-dependent degradation of ubiquitinated proteins. Members function as regulatory subunits within the 26S proteasome complex, which plays a crucial role in maintaining cellular protein homeostasis. They participate in unfolding ubiquitinated target proteins that are then translocated into a proteolytic chamber for degradation into peptides. This process is essential for the removal of misfolded or damaged proteins and for regulating the levels of proteins involved in various cellular processes, including cell cycle progression, apoptosis, and DNA damage repair. Some family members are also implicated in the recognition, binding, and translocation of substrate proteins into the archaeal 20S proteasome core particle, essential for proteolytic gate opening.
Multi Antimicrobial Extrusion (MATE) (MATE_MdtK)
Type: Family

The MATE (Multi Antimicrobial Extrusion) family of proteins are multidrug efflux pumps that confer resistance to a variety of antimicrobial compounds. These proteins function by utilizing ion gradients, primarily sodium or proton motive force, to extrude toxic substances out of the cell, thereby providing a protective mechanism against a range of drugs. Members of the MATE family are characterized by their ability to transport a wide array of substrates, including fluoroquinolones, ethidium bromide, acriflavine, and other cationic compounds. The MdtK subfamily, a subset of the MATE family, is noted for its probable function as a Na(+)/drug antiporter. The efflux activity of MATE proteins is crucial for bacterial survival in environments containing antimicrobial agents, and they play a significant role in the intrinsic and acquired multidrug resistance observed in many pathogenic bacteria.
D-isomer specific 2-hydroxyacid dehydrogenase (D-isomer_2-hydroxyacid_DH)
Type: Family

The D-isomer specific 2-hydroxyacid dehydrogenase family is characterized by enzymes that perform oxidation-reduction reactions on various 2-hydroxyacids. Members of this family catalyze the NADPH-dependent reduction of glyoxylate and hydroxypyruvate to glycolate and glycerate, respectively. They also catalyze the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate, a step in L-serine biosynthesis, and the oxidation of erythronate-4-phosphate to 3-hydroxy-2-oxo-4-phosphonooxybutanoate. Some enzymes within this family display broader substrate specificity, reducing or oxidizing other 2-keto acids. The family includes subfamilies such as GhrB and PdxB, which have distinct substrate specificities. These enzymes play roles in various metabolic pathways, including glyoxylate detoxification, serine biosynthesis, and vitamin B6 metabolism, reflecting their diverse functions in cellular metabolism.
Three Amino acid Loop Extension (TALE) homeobox (TALE_homeobox)
Type: Family

The TALE homeobox family is characterized by a conserved DNA-binding homeodomain, playing pivotal roles in developmental processes across diverse organisms. Members of this family function as transcription factors, regulating gene expression patterns critical for morphogenesis, organ development, and cellular differentiation. They are involved in meristem maintenance, leaf and shoot formation, floral development, and embryogenesis. Some proteins within this family bind specific DNA sequences, such as 5'-TGAC-3', to modulate transcriptional activities. They also form heterodimeric complexes with other homeobox proteins, enhancing DNA-binding specificity and transcriptional regulation. The TALE homeobox proteins are further implicated in hematopoiesis, vascular patterning, and neural development, with some acting as transcriptional activators or repressors in response to retinoid signaling. The family includes several subfamilies like KNOX, MEIS, PBX, and TGIF, each with distinct but overlapping functions contributing to their versatile roles in development and differentiation.
NagZ Beta-hexosaminidase (NagZ_Beta-hexosaminidase)
Type: Family

The NagZ beta-hexosaminidase family is involved in bacterial cell wall peptidoglycan recycling. Members of this family function by cleaving the terminal beta-1,4-linked N-acetylglucosamine (GlcNAc) from peptide-linked peptidoglycan fragments. This enzymatic activity results in the release of free GlcNAc, anhydro-N-acetylmuramic acid, and anhydro-N-acetylmuramic acid-linked peptides. Some family members are also implicated in beta-lactam antibiotic resistance by generating signaling peptides that induce the expression of beta-lactamase enzymes. The family is characterized by its membership in the glycosyl hydrolase 3 family and is found across various bacterial species.
Ras-related protein Rab (Rab)
Type: Family

The Rab protein family is involved in the regulation of intracellular membrane trafficking, which includes the formation, movement, tethering, and fusion of transport vesicles. Members of this family cycle between an inactive GDP-bound form and an active GTP-bound form, recruiting various downstream effectors to maintain organelle identity and morphology. They play roles in processes such as endocytic and secretory pathways, autophagosome assembly, cell adhesion and migration, and neuron projection development. Some Rab proteins are also implicated in the maturation and exocytosis of cytotoxic granules in lymphocytes, the structural integrity of the Golgi apparatus, and the formation of contacts between endoplasmic reticulum and lipid droplets. Additionally, they contribute to the development and function of various tissues, including eyes and brain, and are involved in cellular defense against pathogens.
Carboxylesterase BioH (Carboxylesterase_BioH)
Type: Family

The Carboxylesterase BioH family is part of the AB hydrolase superfamily and is involved in biotin biosynthesis. Members of this family, such as BioH, play a crucial physiological role by removing the methyl group introduced by BioC during the synthesis of the pimeloyl moiety. This demethylation step is essential for the production of pimeloyl-ACP via the fatty acid synthetic pathway, as it involves the hydrolysis of the ester bonds of pimeloyl-ACP esters. This process is a key step in the fatty acid synthetic pathway that leads to the formation of pimeloyl-CoA, a precursor in biotin biosynthesis. The family exhibits esterase activity, with a preference for short-chain fatty acid esters, and may also be involved in the condensation of CoA and pimelic acid.
Thiosulfate sulfurtransferase GlpE (GlpE_sulfurtransferase)
Type: Family

The GlpE family is characterized by proteins that are involved in sulfur metabolism, with a primary function of catalyzing sulfur transfer reactions. Members of this family, such as Thiosulfate sulfurtransferase GlpE, are known to transfer sulfur from thiosulfate to cyanide, albeit with low efficiency, suggesting that these may not be their physiological substrates. The family includes proteins with potential regulatory roles, such as in the response to antitubercular drugs, and others that may participate in oxidative dissimilatory sulfur metabolism as part of a sulfur relay system. The exact physiological roles and substrates for many members remain to be fully elucidated, with some evidence pointing towards interactions with thioredoxin or related dithiol proteins, and possible links to glycerol-phosphate metabolism.
Calmodulin/Myosin light chain/Troponin C-like (CALM/Myosin/TropC-like)
Type: Family

The protein family is involved in calcium-mediated regulation of muscle contraction and cellular processes. Members of the family serve as regulatory proteins in striated muscle contraction, with troponin components (Tn-I, Tn-T, Tn-C) that respond to calcium binding by modulating actomyosin ATPase activity . Other members, such as calmodulins and calglandulins, mediate the control of various enzymes, ion channels, and proteins through calcium signalling . Some light chains of myosin are essential for ATPase activity, while others are regulatory, influencing myosin's interaction with actin . Additionally, the family includes proteins potentially involved in secretion of toxins from venom glands and in cellular control mechanisms . The family showcases a diversity of calcium-binding proteins with roles in muscle function, enzyme regulation, and cellular responses to calcium.
Iron/ascorbate-dependent oxidoreductase (Iron_ascorbate_oxido_reductase)
Type: Family

The iron/ascorbate-dependent oxidoreductase family is involved in a wide range of biosynthetic processes, including the production of antibiotics, plant hormones, and secondary metabolites with various biological activities. Members of this family function as 2-oxoglutarate-dependent dioxygenases, catalyzing hydroxylation reactions that are essential for the biosynthesis of cyclic peptides, gibberellins, and other compounds. These enzymes play crucial roles in fungal cell wall formation inhibition, plant development regulation through gibberellin catabolism, and the formation of bioactive compounds with antifungal, antibacterial, and antitumor properties.
F-box/LRR-repeat protein 13/AtMIF1-like (FBL13/AtMIF1-like)
Type: Family

This entry includes F-box/LRR-repeat containing proteins from plants, such as F-box/LRR-repeat protein 13 and AtMIF1 (also known as F-box protein AT3G62230) from Arabidopsis. These proteins are involved in the ubiquitin-proteasome pathway. Members of the family function as components of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complexes . These complexes play a crucial role in the selective degradation of proteins by tagging them with ubiquitin, which signals for their degradation by the 26S proteasome . AtMIF1 physically interacts with MYB domain protein 5 (MYB5), which results in MYB5 degradation representing a new regulatory pathway, 26S proteasome-AtMIF1-MYB5 that regulates oil content of seeds, increasing their oil content without affecting plant growth, thus facilitating oil crop breeding .

The F-box domain present in these proteins is essential for the interaction with SKP1 (ASK in Arabidopsis), which is a part of the SCF complex. The LRR (leucine-rich repeat) domain suggests that these proteins may be involved in protein-protein interactions, potentially recognizing specific substrate proteins for ubiquitination. This family plays a significant role in various cellular processes by regulating the abundance of key proteins.
Arabidopsis thaliana F-box (A_thaliana_F-box)
Type: Family

The Arabidopsis thaliana F-box protein family is involved in various regulatory processes through the ubiquitin-proteasome pathway. Members of the family function as part of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complexes, which target proteins for ubiquitination and subsequent degradation. This post-translational modification is crucial for plant growth, development, and stress responses. Specific members within the family, such as ETP1 and ETP2, act as negative regulators of EIN2 protein stability, affecting ethylene signaling. Others, like SUPPRESSOR OF NIM1 1, negatively regulate plant defense pathways independent of salicylic acid. The diversity of the F-box domain and associated motifs, such as kelch repeats or leucine-rich repeats, suggests a wide range of substrates and functions.
Nuclear hormone receptor family NR1 subfamily (Nuclear_hormone_rcpt_NR1)
Type: Family

The nuclear hormone receptor family NR1 subfamily consists of ligand-activated transcription factors that play pivotal roles in the regulation of development, metabolism, and immune functions. Members of this family are characterized by a modulating N-terminal domain, a central DNA-binding domain, and a C-terminal ligand-binding domain. They function as receptors for various endogenous hormones, including thyroid hormones, oxysterols, bile acids, and vitamin D3, as well as for xenobiotic compounds. These receptors can act as repressors or activators of transcription, depending on the presence of their respective ligands. They are involved in diverse biological processes such as cholesterol homeostasis, lipid metabolism, circadian rhythm regulation, and glucose homeostasis. The NR1 subfamily includes thyroid hormone receptors, oxysterols receptors, bile acid receptor, and vitamin D3 receptor, among others, highlighting their broad impact on physiological functions.
Casein Kinase 1 Ser/Thr Protein Kinase (CK1_Ser-Thr_kinase)
Type: Family

The Casein Kinase 1 (CK1) family is a group of serine/threonine-protein kinases that share a preference for acidic proteins such as caseins as substrates. Members of this family are involved in a wide range of cellular processes, including Wnt signaling, circadian rhythms, DNA repair, cell cycle regulation, and vesicular trafficking. They are known to phosphorylate a large number of proteins, influencing various signaling pathways and cellular functions. Some isoforms play key roles in the regulation of the circadian clock by determining the period length through phosphorylation of PER1 and PER2, controlling their nuclear transport and degradation. Others are involved in ciliogenesis, spermatogenesis, and responses to DNA damage. The family also includes pseudokinases that participate in viral DNA replication repression and regulation of host defense mechanisms.
Serine/threonine-protein kinases, AGC (Ser_Thr_kinase_AGC)
Type: Family

The protein family includes serine/threonine kinases that play key roles in various cellular processes such as cell cycle progression, cell structure, proliferation, apoptosis, migration, adhesion, and transcription regulation. They are involved in signaling pathways that control organ size, tumor suppression, and cellular responses to stress and external stimuli. Members of this family phosphorylate a range of substrates, modulating their activity and localization, which is crucial for maintaining cellular integrity and responding to environmental changes. They are also implicated in the regulation of metabolic pathways, immune responses, and developmental processes.
ATP-dependent AMP-binding enzyme (ATP-dep_AMP-bd_enzyme)
Type: Family

The ATP-dependent AMP-binding enzyme family is characterized by its role in the activation and transfer of carboxylate groups in various biochemical pathways. Members of this family catalyze the formation of acyl-adenylate intermediates using ATP, which are then typically transferred to specific carrier proteins or converted into CoA thioesters. This process is crucial for the biosynthesis of siderophores, secondary metabolites, and the metabolism of fatty acids, sterols, and aromatic compounds. The family includes enzymes involved in the regeneration of phosphatidylethanolamine from lysophospholipids, the biosynthesis of menaquinone, and the degradation of lignin-derived compounds. Enzymes in this family are also implicated in the biosynthesis of antibiotics, pigments, and the assimilation of sulfur compounds in marine ecosystems.
DNA Replication and Repair Clamp Loader Complex (DNA_Rep/Repair_Clamp_Loader)
Type: Family

This family of proteins is involved in DNA replication and repair processes. Members function as part of larger protein complexes that are essential for the elongation of primed DNA templates by DNA polymerases, particularly polymerase delta and epsilon. They play a role in loading sliding clamps, such as PCNA, onto DNA, which is a critical step in DNA replication to ensure processivity of the polymerase enzymes. Some family members also possess ATPase activity and are involved in cellular processes like chromatin assembly and remodeling, as well as in the regulation of cell proliferation and the establishment of sister chromatid cohesion during DNA replication. Additionally, certain proteins within this family act as key regulators of cellular structures, such as trichome branching in plants, through pathways independent of DNA replication.
Sigma-70 factor family, RNA polymerase initiation factors (Sigma-70_RNA_pol_init_factors)
Type: Family

The Sigma-70 factor family consists of initiation factors that promote the attachment of RNA polymerase to specific initiation sites in the DNA during transcription and are subsequently released. Members of this family are involved in various cellular processes, including exponential growth, stationary phase, stress responses, sporulation, and photosynthetic efficiency in plastids. They contain conserved domains that mediate interaction with promoter DNA elements and RNA polymerase subunits, facilitating the melting of double-stranded DNA and the formation of the transcription bubble. Some sigma factors are also regulated by anti-sigma factors and proteases, indicating a complex regulatory network that controls their activity. The family includes primary sigma factors responsible for the majority of gene transcription during exponential growth, as well as specialized sigma factors that regulate gene expression in response to environmental changes and cellular differentiation.
DNA polymerase type-B (DNA_pol_type-B)
Type: Family

The DNA polymerase type-B family is characterized by its essential role in DNA replication and repair. Members of this family exhibit DNA-directed DNA polymerase activity, often coupled with a 3' to 5' exonuclease proofreading function, which enhances the fidelity of DNA synthesis. The family includes both cellular and viral polymerases. Viral DNA polymerases are typically involved in the replication of viral genomic DNA and are part of a replication complex that may include additional viral proteins such as processivity factors, primase, helicase, and ssDNA-binding proteins. Some viral polymerases also possess an intrinsic ribonuclease H (RNase H) activity for the degradation of RNA/DNA heteroduplexes. Cellular DNA polymerases within this family, such as DNA polymerase delta, play a crucial role in high-fidelity genome replication, including lagging strand synthesis, and are involved in DNA repair processes. They often require accessory proteins like PCNA for full activity and can be regulated by various factors, including quaternary structure alterations and interaction with other proteins.
NAD-capped RNA hydrolase NudC subfamily (NAD-cap_RNA_hydrolase_NudC)
Type: Family

The NudC subfamily of Nudix hydrolases is characterized by its ability to catalyze the hydrolysis of NAD-capped RNA, specifically removing the nicotinamide adenine dinucleotide (NAD) cap from a subset of mRNAs. This decapping activity results in the production of nicotinamide mononucleotide (NMN) and 5' monophosphate mRNA. The presence of the NAD cap at the 5'-end of mRNAs generally serves to stabilize the RNA against 5'-processing. Members of the NudC subfamily exhibit a preference for mRNAs that begin with a purine at the 5'-end and are capable of hydrolyzing a broad range of dinucleotide pyrophosphates. This decapping mechanism is distinct from the canonical removal of the N7 methylguanosine (m7G) cap, and in some cases, the NAD cap promotes mRNA decay. The NudC subfamily plays a role in regulating mRNA stability and turnover, impacting gene expression and cellular metabolism.
JAMM/MPN+ metalloenzymes, peptidase M67A (JAMM_MPN+_peptidase_M67A)
Type: Family

The peptidase M67A family, also known as the JAMM/MPN+ metalloenzymes, encompasses proteins with diverse functions related to ubiquitin signaling and protein homeostasis. Members of this family are involved in the cleavage of 'Lys-63'-linked polyubiquitin chains, regulating processes such as DNA damage response, cell cycle progression, and immune signaling. They are components of various multiprotein complexes, including the BRCA1-A complex, which targets DNA damage sites, and the BRISC complex, which is essential for mitotic spindle assembly. The family also includes subunits of the COP9 signalosome, which regulates ubiquitin conjugation pathways, and the 26S proteasome, which degrades ubiquitinated proteins. Additionally, they play roles in translation initiation as part of the eIF-3 complex, targeting specific mRNAs for protein synthesis. This family is characterized by the presence of a JAMM motif, which is crucial for their protease activity, and some members also contain SANT and SWIRM domains for DNA binding and chromatin association.
Probable phosphatase PHP (PHP_phosphatase)
Type: Family

The PHP family proteins are characterized by their probable phosphatase activity, which suggests a role in hydrolyzing phosphate groups from various substrates. A specific member, YcdX from E. coli, has been noted to hydrolyze p-nitrophenyl phosphate (pNPP) in vitro and is implicated in swarming motility, with its activity being stimulated by YcdY. The broader function of the PHP family may involve diverse roles in cellular processes that require phosphatase activity, although the specific substrates and biological functions may vary among different family members.
Autonomous Glycyl Radical Cofactor (Auton_GlycylRad_Cofactor)
Type: Family

The Autonomous Glycyl Radical Cofactor family comprises proteins that serve as radical domains for damaged pyruvate formate-lyase (PFL) and potentially other radical proteins. Members of this family are involved in the recovery of radical enzymes by acting as a scaffold that stabilizes the radical species, which is essential for the catalytic activity of these enzymes. The proteins within this family are characterized by their ability to harbor and stabilize a glycyl radical, which is crucial for the function of radical-dependent enzymes, particularly under anaerobic conditions where such enzymes play a vital role in energy metabolism and various biosynthetic processes.
Bacterial extracellular foldase PrsA (PrsA_foldase)
Type: Family

The PrsA family proteins are essential foldases that play a pivotal role in protein secretion processes. They assist in the post-translocational extracellular folding of various secreted proteins. Members of the PrsA family are involved in the production of active forms of enzymes and toxins, contributing to the stability and function of these extracellular proteins. Some members have peptidyl-prolyl cis-trans isomerase (PPIase) activity, although this is not always essential for their function in vivo. The PrsA proteins may exhibit different substrate specificities, indicating a degree of functional specialization within the family.
Class II Fructose-bisphosphate Aldolase (Class_II_FBP_aldolase)
Type: Family

The class II fructose-bisphosphate aldolase family is involved in key metabolic processes, such as glycolysis and gluconeogenesis, by catalyzing the reversible aldol condensation of dihydroxyacetone phosphate with glyceraldehyde 3-phosphate to form fructose 1,6-bisphosphate. Some members also participate in the catabolism of galactitol and the metabolism of tagatose 1,6-bisphosphate, as part of the tagatose-1,6-bisphosphate aldolase complex, which requires a GatZ subunit for full activity and stability. Additionally, a subfamily within this group is responsible for producing dihydroxyacetone phosphate and malonic semialdehyde from 6-phospho-5-dehydro-2-deoxy-D-gluconate. The family includes various subunits like GatY and KbaY, indicating a diversity of functions and substrate specificities within the broader context of carbohydrate metabolism.
Methionine Aminopeptidase Type 2 (Met_Aminopeptidase_Type2)
Type: Family

The Methionine Aminopeptidase Type 2 family is characterized by its role in the cotranslational processing of nascent proteins. Members of this family are responsible for the cleavage of the N-terminal methionine from newly synthesized proteins when the second residue is small and uncharged, which includes amino acids such as alanine, cysteine, glycine, proline, serine, threonine, or valine. This enzymatic activity is crucial for proper protein maturation and function. Additionally, in humans and some other species, these enzymes protect the eukaryotic initiation factor EIF2S1 from inhibitory phosphorylation, thereby playing a critical role in the regulation of protein synthesis. The family includes both eukaryotic and archaeal subtypes, with some members being subject to inhibition by compounds such as fumagillin and its analogs, which have antiangiogenic properties.