SII-SWORD/CoKE huggingface dataset:
Voltage-dependent calcium channel alpha-1 subunit (VDCC_alpha-1_subunit)
Type: Family

Voltage-dependent L-type calcium channel subunit alpha-1S and related proteins are essential for the mediation of calcium ion entry into excitable cells, triggering a variety of calcium-dependent processes such as muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, division, and cell death. These proteins form high-voltage activated (HVA) channels, which are characterised by their long-lasting calcium currents and sensitivity to specific blockers like dihydropyridines, phenylalkylamines, and benzothiazepines . The family includes subunits that give rise to different types of calcium currents, such as L-type, P/Q-type, N-type, and R-type, each with distinct physiological roles and pharmacological profiles . The domain architecture of these proteins typically features four internal repeats, each containing six transmembrane segments, with the fourth segment acting as the voltage sensor. This family plays a crucial role in excitation-contraction coupling in muscle and is involved in various signaling pathways critical for cellular function and survival.
SETD3/SETD6 methyltransferase (SETD3_SETD6_MTase)
Type: Family

The SETD3/SETD6 protein family encompasses a group of S-adenosyl-L-methionine (SAM)-dependent methyltransferases that share a common function in post-translational modification of proteins through methylation. Members of the family exhibit specificity for different substrates, including actin, histones, and various ribosomal proteins. The SETD3 subfamily members are protein-histidine N-methyltransferases, specifically targeting actin at histidine residues, which is crucial for muscle contraction during labor. The SETD6 subfamily members are protein-lysine N-methyltransferases, with functions ranging from transcriptional regulation, as seen with the methylation of the RELA subunit of NF-kappa-B, to the maintenance of embryonic stem cell self-renewal. Other family members methylate lysine residues on cytochrome c, elongation factors, and ribosomal proteins, indicating a broad role in cellular processes such as proliferation, differentiation, and response to inflammation.
CPA3 antiporter subunit C (CPA3_antiporter_subunitC)
Type: Family

The CPA3 antiporter subunit C family comprises membrane proteins involved in cation/H+ antiport activity, primarily functioning in Na+ and/or Li+ excretion and resistance. These antiporters play a significant role in maintaining pH homeostasis and osmotic balance within the cell. They are electrogenic, utilizing a transmembrane electrical potential to drive the exchange of Na+ or Li+ for H+. The family members are essential for various physiological processes, including sporulation initiation under high external Na+ concentrations and adaptation to alkaline pH during symbiotic nodule development in certain species. While the primary function is Na+/H+ antiport, some members are also implicated in K+/H+ exchange and may be part of larger complexes with additional roles, such as NADH-ubiquinone oxidoreductase activity.
Malonyl-ACP O-Methyltransferase (Malonyl-ACP_OMT)
Type: Family

The Malonyl-ACP O-Methyltransferase family is characterized by enzymes that modify malonyl-thioesters, converting the free carboxyl group to its methyl ester using S-adenosyl-L-methionine (SAM) as the methyl donor. This methylation step is crucial for the synthesis of pimeloyl-ACP, an intermediate in the fatty acid synthetic pathway. Some family members, such as BioHC proteins, have a bifunctional role, also participating in the removal of the methyl group from pimeloyl-ACP esters, thus completing the pimeloyl moiety. Additionally, a subset of proteins within this family, like NDUFAF5, are involved in the assembly of mitochondrial complexes, indicating a potential dual functionality with both methyltransferase and hydroxylase activities.
MYST family histone acetyltransferases (MYST_HAT)
Type: Family

The MYST family of histone acetyltransferases (HATs) plays a crucial role in the regulation of gene expression through the acetylation of histone proteins, which alters chromatin structure and facilitates transcriptional activation. Members of this family are involved in various cellular processes, including DNA repair, cell cycle progression, development, and autophagy. They acetylate multiple lysine residues on histones H3, H4, and H2A, impacting epigenetic transcription initiation and elongation. Some family members also acetylate non-histone proteins, influencing activities beyond chromatin remodeling. The family's acetyltransferase activity is regulated by phosphorylation, autoacetylation, and interaction with other proteins, and can use various acyl-CoA substrates for acetylation, crotonylation, and 2-hydroxyisobutyrylation, indicating a versatile role in epigenetic and metabolic regulation.
PDZ and LIM domain-containing (PDZ-LIM_domain)
Type: Family

The PDZ and LIM domain protein family is involved in a variety of cellular processes including the organization of the cytoskeleton, cell migration, and maintaining cell polarity. Members act as molecular adapters, linking proteins to the cytoskeleton and coordinating protein-protein interactions at focal adhesions and in the nucleus. They play roles in signaling pathways such as Wnt and TGFB, and in the regulation of receptors and transcriptional activity of nuclear receptors. Some family members are involved in heart development, bone formation, and the regulation of synaptic receptor transport and postsynaptic growth in neurons. They may also function as scaffolds for assembling protein complexes and have roles in muscle cell actin filament organization.
Olfactomedin-like domain-containing protein (Olfactomedin-like_domain)
Type: Family

This family of proteins includes secreted and membrane-associated factors with diverse biological functions, primarily related to cell signaling, development, and maintenance of cellular structures. Members are involved in processes such as cell adhesion, migration, cytoskeleton organization, and differentiation. They play roles in the formation and maintenance of the nodes of Ranvier in neurons, dorsoventral patterning during development, and may influence cell proliferation in cancer. Some family members are implicated in the regulation of smooth muscle cell phenotype, bone formation, myelination, muscle hypertrophy, and neurite outgrowth. They are characterized by the presence of an olfactomedin-like domain, which mediates protein-protein interactions and contributes to their diverse functions.
Calponin-like (Calponin-like)
Type: Family

This family of proteins is associated with the regulation and modulation of smooth muscle contraction. Members are known to bind to actin, calmodulin, and tropomyosin, and their interaction with actin inhibits the actomyosin Mg-ATPase activity. Some family members are implicated in actin filament dynamics, including actin cross-linking, bundling, and stabilization against disassembly. They may also contribute to the maintenance of sarcomeric actin organization in striated muscles and play roles in cellular contractile properties, potentially influencing replicative senescence and cell migration.
Nitric Oxide Synthase (NOS) (NOS)
Type: Family

The Nitric Oxide Synthase (NOS) family is responsible for the production of nitric oxide (NO), a versatile messenger molecule with a wide range of biological functions. Members of the NOS family catalyze the conversion of L-arginine to L-citrulline, releasing NO in the process. NO plays a critical role in various physiological processes including neurotransmission, vascular smooth muscle relaxation, immune response, and regulation of gene expression. The family includes inducible forms that are stimulated by inflammatory signals and constitutive forms that are regulated by calcium/calmodulin. Some NOS proteins also exhibit nitrosylase activity, mediating the S-nitrosylation of cytoplasmic target proteins, which can affect their function and activity.
NmrA-type oxidoreductase, Isoflavone reductase subfamily (NmrA-type/Isoflavone_red_sf)
Type: Family

The NmrA-type oxidoreductase family, specifically the Isoflavone reductase subfamily, encompasses enzymes involved in plant secondary metabolite biosynthesis. Members of this family play crucial roles in the biosynthesis of lignans, isoflavonoids, and alkaloids, which are important for plant defense mechanisms and interactions with the environment. They catalyze the reduction of various substrates such as isoflavones, pinoresinol, lariciresinol, and phenylcoumaran benzylic ethers, using NADPH as a cofactor. These enzymes contribute to the production of phytoalexins, lignans, and alkaloids with properties ranging from antimicrobial, antiparasitic, and pesticide to the formation of carcinogenic compounds. Additionally, some members are involved in the synthesis of phenylpropenes like eugenol and isoeugenol, which serve as floral attractants and defense compounds. The diversity of reactions catalyzed by this family reflects their significant role in plant biochemistry and the potential for biotechnological applications.
Antp homeobox family, Deformed subfamily (Antp_homeobox_Deformed_sf)
Type: Family

The Antp homeobox family, specifically the Deformed subfamily, consists of sequence-specific transcription factors that are integral to a developmental regulatory system. These proteins confer specific positional identities to cells along the anterior-posterior axis during development. Members of the family are characterized by their ability to bind DNA at specific sites, influencing the transcription of genes involved in establishing body plans and segmental identities. The family plays a crucial role in the development of various species, from invertebrates to vertebrates, indicating a highly conserved function across different phyla. The proteins typically contain a homeobox domain that facilitates DNA binding, and some members have been shown to activate transcription of apoptotic activators or regulate gene expression related to cell fate specification and organ development.
APOBEC Cytidine Deaminase (APOBEC_Cyt_Deaminase)
Type: Family

The APOBEC family of cytidine deaminases plays a crucial role in the immune response against viruses and in genome maintenance. Members of this family can induce the conversion of cytosine to uracil in single-stranded DNA, leading to hypermutations that can inhibit retrovirus replication and retrotransposon mobility. Some family members are also involved in RNA editing, such as the conversion of cytidine to uridine in mRNA, and may participate in DNA demethylation, contributing to the epigenetic regulation of gene expression. The family includes enzymes with antiviral activity against HIV, SIV, HBV, HTLV-1, and other viruses. They are regulated by factors such as the HIV-1 virion infectivity factor (Vif), which can neutralize their activity. The family is characterized by the presence of one or two CMP/dCMP deaminase domains that confer substrate specificity and mediate various functions, including RNA binding, oligomerization, and virion incorporation.
ATP-binding cassette sub-family F member, EF3 subfamily (ABCF_EF3_subfamily)
Type: Family

The ABCF family, EF3 subfamily, consists of ribosome-dependent ATPases involved in various aspects of protein synthesis and cellular processes. Members of this family are required for the ATP-dependent release of deacylated tRNA from the ribosomal E-site during protein biosynthesis and stimulate the binding of aminoacyl-tRNA to the ribosomal A-site. Some members display antiviral effects against flaviviruses in the presence of OAS1B, while others may be involved in ribosome assembly or function, mRNA export, and regulation of GCN2 kinase activity in response to amino acid availability. Additionally, certain proteins within this family are implicated in ribosome biogenesis and the ribosome-associated quality control pathway.
Prokaryotic Molybdopterin Oxidoreductases (Prok_Mopterin_Oxidored)
Type: Family

The Prokaryotic Molybdopterin-containing Oxidoreductase family comprises enzymes that catalyze various anaerobic redox reactions, often linked to energy conservation. Members of this family are involved in the reduction of compounds such as trimethylamine-N-oxide (TMAO), dimethyl sulfoxide (DMSO), tetrathionate, thiosulfate, selenate, chlorate, and arsenate, using them as terminal electron acceptors. These enzymes are characterized by the presence of a molybdopterin guanine dinucleotide cofactor in their active sites. They play crucial roles in the anaerobic metabolism of bacteria, allowing them to thrive in environments where oxygen is scarce or absent. The family includes enzymes like TMAO reductase, which converts TMAO to trimethylamine, and DMSO reductase, which reduces DMSO to dimethyl sulfide. Other members are involved in the detoxification of toxic compounds, such as arsenate reductase, which reduces arsenate to arsenite. The diversity of substrates reflects the versatility of this family in utilizing different electron acceptors for anaerobic respiration.
Secondary Metabolite Biosynthesis Regulators (Sec_Metabolite_Reg)
Type: Family

The protein family is composed of transcription factors that regulate the expression of gene clusters involved in the biosynthesis of various secondary metabolites, including antibiotics, mycotoxins, and other bioactive compounds. These transcription factors typically contain a C6 finger domain and are involved in the specific regulation of biosynthetic pathways for compounds such as neosartoricin, viridicatumtoxin, fusarisetin A, and others. They play crucial roles in the production of metabolites with functions ranging from antimicrobial activity to the regulation of azole responses. Members of the family are also involved in the regulation of efflux pumps and may participate in the detoxification of toxic compounds within the producing organisms.
Synaptic Scaffolding LAP/MAGUK Families (Synaptic_Scaffolding_LAP-MAGUK)
Type: Family

The LAP (LRR and PDZ) and MAGUK protein families are involved in synaptic function and cellular signaling. Members of these families are essential for synaptic plasticity, synaptogenesis, and maintaining synaptic architecture. They serve as scaffolding proteins, clustering crucial synaptic proteins at postsynaptic densities and regulating the surface expression of receptors like NMDA and AMPA. Some family members are involved in cell polarity, proliferation, migration, and apoptosis, playing roles in epithelial and neuronal morphogenesis, T-cell polarization, and pain perception. They may also influence signal transduction pathways, including Wnt and Rho, and modulate the trafficking of channels and receptors within cells.
ATP-dependent DNA Helicase (ATP-dep_DNA_Helicase)
Type: Family

This family of proteins includes ATP-dependent DNA helicases that are involved in various cellular processes such as transcription, nucleotide excision repair (NER), and postreplicative transcription termination. Members of this family are capable of unwinding DNA in a 3'-5' direction and are essential for DNA repair by opening DNA around lesions. They also play a crucial role in transcription initiation by RNA polymerase II, facilitating promoter opening and escape. Some proteins within this family form stable complexes with single-stranded DNA and, to a lesser extent, RNA, and are implicated in the ATP-dependent release of nascent RNA transcripts.
CPA3 Na+/H+ Antiporter Subunit A (CPA3_Na-H_Antiporter_A)
Type: Family

This family of proteins includes antiporters that are primarily involved in the exchange of sodium (Na+) and hydrogen (H+) ions across the cell membrane. These antiporters contribute to the maintenance of cellular ion homeostasis, pH regulation, and adaptation to high sodium environments. They utilize the electrochemical gradient to drive the transport of Na+ out of the cell in exchange for H+ ions, which is inferred to be an electrogenic process. The family members are characterized by their inability to transport other cations such as potassium (K+), calcium (Ca2+), or magnesium (Mg2+). Some proteins in this family are also implicated in the excretion of lithium (Li+) ions and may have a role in the resistance to high sodium conditions. Additionally, certain members are sensitive to inhibitors like carbonyl cyanide m-chlorophenylhydrazone (CCCP), which can completely inhibit Na+ extrusion.
E3 ubiquitin-protein ligases and FN3/SPRY domain-containing proteins (E3_ligase_FN3/SPRY)
Type: Family

This family of proteins includes E3 ubiquitin-protein ligases and proteins with fibronectin type III and SPRY domains. Members of this family are involved in various cellular processes, including ubiquitination and proteasomal degradation of target proteins, which can influence cell cycle regulation and chromosome segregation. Some proteins within this family mediate spermatid-Sertoli adhesion during spermatogenesis, potentially affecting fertility. Others may act as regulators of adipogenesis, microtubule organization, and stabilization, or serve as anchoring proteins for protein kinase A, influencing muscle function and regeneration. Additionally, certain family members are implicated in neuronal functions, such as synaptic vesicle exocytosis, axonal projections, and neuronal migration, by interacting with components like SNAP25 or through ubiquitin ligase activity.
Ubiquitination and Signaling Pathway Regulator (Ubq-SigPath_Reg)
Type: Family

The protein family is involved in various cellular processes including ubiquitination, signaling pathways, and intracellular trafficking. Members act as core components of the CTLH E3 ubiquitin-protein ligase complex, mediating ubiquitination and proteasomal degradation of specific target proteins such as HBP1. Some family members function as guanine nucleotide exchange factors for RAN GTPase, influencing microtubule dynamics and hemostasis. They also play roles in the Wnt signaling pathway by promoting beta-catenin nuclear accumulation. Additionally, they are implicated in the endosome-vacuole trafficking pathway, regulating nutrient transport and determining the fate of plasma membrane proteins. The family includes proteins with a SPRY domain that mediates interactions with various receptors and signaling molecules.
Flavodoxin (Flavodoxin)
Type: Family

The flavodoxin family comprises proteins that function as low-potential electron donors to various redox enzymes. Members of this family are involved in a range of electron transport systems in microorganisms and are known to contribute to processes such as nitrogen fixation by donating electrons to nitrogenase. Some flavodoxins are also implicated in the reactivation of inactive cob(II)alamin in methionine synthase, an essential step in the biosynthesis of methionine. The family is characterized by the ability to stabilize their structure upon cofactor binding and is functionally interchangeable with ferredoxins in some biological systems.
Thioredoxin H-type-like (Thioredoxin_H-type-like)
Type: Family

This family of proteins is involved in redox regulation, acting as thiol-disulfide oxidoreductases. They participate in various redox reactions by reversibly oxidizing their active center dithiol to a disulfide, which can activate or regulate a number of cytosolic enzymes . Some members are known to play roles in response to pathogens, oxidative stresses, and in the regulation of MAP kinases. Thioredoxin domain-containing protein 2 from mouse, may be involved in processes such as sperm development and fibrous sheath assembly in sperm tail morphogenesis. Additionally, they are implicated in the biosynthesis of host-selective toxins in certain plant pathogens.
Tudor domain-containing (Tudor_domain_containing)
Type: Family

The Tudor domain-containing protein family is involved in various aspects of germ cell development and maintenance of germline integrity. Members of the family participate in the piRNA metabolic process, which is crucial for the repression of transposable elements during meiosis, thereby preventing their mobilization. This process involves the formation of complexes composed of piRNAs and Piwi proteins, which are essential for the methylation and subsequent repression of transposons. The family also plays a role in post-transcriptional regulation of gene expression by binding to specific mRNAs and regulating their translation in cytoplasmic RNA granules. This regulation is necessary for processes such as lens transparency during lens development and spermatogenesis. Additionally, some family members are involved in the assembly of the chromatoid body, the formation of the Balbiani body during oogenesis, and the maturation of the spliceosome and miRNA expression.
CPA3 Na(+)/H(+) Antiporter Subunit B (CPA3_antiporter_subunitB)
Type: Family

The CPA3 antiporter subunit B family comprises proteins that function as Na(+)/H(+) antiporters involved in the excretion of sodium ions. These antiporters are part of larger complexes, such as the Mnh complex in various Staphylococcus species and the Mrp complex in Bacillus subtilis, which play significant roles in Na(+) resistance and pH homeostasis. The antiport activity is electrogenic, consuming a transmembrane electrical potential to transport Na(+) in exchange for H(+), and is inhibited by CCCP. While primarily transporting Na(+), some family members also transport Li(+) but not K(+), Ca(2+), or Mg(2+). The antiporters are essential for maintaining intracellular pH and sodium ion concentration, especially under alkaline conditions or high external Na(+) concentrations.
Periplasmic Glucan Succinylation Acyltransferase (Glucan_succinyl_AcylTrfase)
Type: Family

The OpgC protein family is involved in the biosynthesis of periplasmic glucans, specifically in the succinyl substitution process. Members of this family are believed to function as acyltransferases, catalyzing the transfer of succinyl residues from the cytoplasmic side of the bacterial inner membrane to the growing glucan chains located in the periplasm. This modification of glucans is crucial for the proper function and structural integrity of the bacterial cell envelope, potentially affecting cell shape, protection against environmental stresses, and interaction with host immune systems during pathogenesis.
HTH-type Transcriptional Regulator (HTH-type_Tx_Regulator)
Type: Family

This family of proteins includes helix-turn-helix (HTH) type transcriptional regulators that are involved in various cellular processes. Members of this family can act as repressors or activators of gene transcription, often in response to specific environmental or intracellular signals. Some proteins in this family are known to regulate the transcription of operons responsible for biofilm production, fatty acid metabolism, and antibiotic resistance. They typically function by binding to specific DNA sequences, thereby influencing the transcription of downstream genes. The regulatory mechanisms may involve repression of operon transcription necessary for biofilm formation, negative regulation of fatty acid degradation gene transcription, or control of cell envelope permeability to hydrophobic compounds. The activity of these proteins can be modulated by factors such as the presence of fatty acids or cationic lipophilic compounds.