SII-SWORD/CoKE huggingface dataset:
Peptidase S1 family, Elastase subfamily (Peptidase_S1_Elastase_sf)
Type: Family

The elastase subfamily within the peptidase S1 family comprises serine proteases with diverse functions, including the degradation of various proteins such as elastin, fibronectin, laminin, vitronectin, and collagen types I, III, and IV. Members of this family play significant roles in physiological processes like insulin signaling, glucose metabolism, and modulation of immune cell functions. They are involved in cellular processes such as neutrophil transendothelial migration and can exhibit antimicrobial activity by degrading bacterial proteins. Some members specifically target zymogen precursors of digestive enzymes, regulating their activation and degradation. The family includes enzymes with specificity for alanine and limited elastolytic activity, as well as those that hydrolyze many proteins beyond elastin.
mRNA Cap 2'-O-Ribose Methyltransferase (mRNA_Cap_2O-Ribose_MeTrfase)
Type: Family

The protein family includes S-adenosyl-L-methionine-dependent methyltransferases that are responsible for the methylation of the ribose moiety at the 5'-cap of mRNAs and small nuclear RNAs. Members of the family catalyze the transfer of a methyl group to the 2'-O position of the ribose of the first or second nucleotide next to the cap structure, producing cap1 (m(7)GpppRm) or cap2 (m(7)GpppRmpNm) modifications, respectively. These modifications are crucial for enhancing translation efficiency and may play a role in the interferon response pathway. Some members show a preference for cap0 (unmethylated) transcripts, while others can methylate both cap0 and cap1 structures. The family also includes viral proteins that methylate the cap structure of late viral transcripts, as well as uncharacterized proteins that are likely to share similar functions.
Queuine tRNA-ribosyltransferase (Queuine_tRNA-ribosyltrfase)
Type: Family

The Queuine tRNA-ribosyltransferase family is involved in the modification of tRNA molecules. Specifically, the QTRT2 subfamily members act as non-catalytic subunits in the queuine tRNA-ribosyltransferase (TGT) complex. This complex is responsible for the base-exchange of a guanine residue with queuine at the anticodon wobble position 34 in tRNAs that recognize codons starting with guanine (GU(N) anticodons). The tRNAs targeted include those for aspartic acid, asparagine, histidine, and tyrosine. The result of this modification is the formation of the hypermodified nucleoside queuosine, which is essential for accurate and efficient protein synthesis. Queuosine is known for its role in the translational regulation and maintenance of the stability and structure of tRNA.
WD repeat-containing DNA damage-binding protein (WD_repeat_DNA-damage-binding)
Type: Family

This family of proteins includes members that are involved in DNA-binding and recognition of specific DNA modifications. They are known to bind to both single- and double-stranded DNA, with a preference for UV-damaged DNA, suggesting a role in DNA repair and maintenance. Some family members have been identified as specific readers of the modified DNA base 5-hydroxymethylcytosine (5hmC), which is important in epigenetic regulation. The presence of WD repeats indicates a potential role in protein-protein interactions, which may be crucial for their function in DNA-metabolic processes.
Lysosomal Cobalamin Transport Escort Protein LMBD1 (LMBD1_LysCbl_Transport)
Type: Family

The LMBRD1 subfamily of the LIMR family is characterized by proteins that function as lysosomal cobalamin transporters. These proteins are essential for the export of cobalamin, also known as vitamin B12, from lysosomes to the cytosol. This export is a critical step in allowing the conversion of cobalamin into its active cofactor forms. Members of the LMBRD1 subfamily are also involved in targeting the ABCD4 transporter to the lysosome and forming a complex with ABCD4 and MMACHC to facilitate cobalamin transport across the lysosomal membrane. Additionally, some family members act as adapter proteins that mediate and regulate the internalization of the insulin receptor, and are involved in clathrin-mediated endocytosis. They play a role in early embryogenesis, particularly in the initiation of gastrulation and formation of mesoderm structures.
Metallo-beta-lactamase type 2-like (NDM-1-like)
Type: Family

This entry represents Metallo-beta-lactamase type 2 from Klebsiella pneumoniae (NDM-1) and similar enzymes that share a common fold and metal-binding motif but can have different functions. NDM-1 confers resistance to the different beta-lactams antibiotics (penicillin, cephalosporin and carbapenem) via the hydrolysis of the beta-lactam ring , thereby conferring resistance. Some family members exhibit acyl-CoA thioesterase activity, catalysing the hydrolysis of acyl-CoAs to free fatty acids and CoASH, which may regulate intracellular levels of these molecules . Others are involved in the degradation of specific compounds, such as 2,4-dinitroanisole , or play roles in the biosynthesis of signalling molecules important for biofilm formation and virulence. The family also includes uncharacterised proteins that may have metallo-hydrolase activity.
Biotin-dependent Carboxylase Complex (Biotin_carboxylase_complex)
Type: Family

The protein family is involved in various biotin-dependent carboxylation reactions essential for metabolizing fatty acids, amino acids, and other compounds. Members possess a biotin carboxylation/carboxylase (BC) domain that transiently carboxylates biotin, and a biotinyl-binding/biotin carboxyl carrier (BCC) domain for biotin attachment. Key reactions include the conversion of propionyl-CoA to D-methylmalonyl-CoA, crucial in the catabolism of odd chain fatty acids and branched-chain amino acids, and the transformation of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA, vital for leucine catabolism. Some members also participate in the carboxylation of acetyl-CoA to form malonyl-CoA, pyruvate carboxylation to oxaloacetate, and urea hydrolysis. The family's enzymes are involved in mitochondrial and cytoplasmic processes, playing a significant role in cellular energy metabolism and biosynthetic pathways.
D-isomer specific 2-hydroxyacid dehydrogenases (D-2-hydroxyacid_DH)
Type: Family

This family of proteins includes enzymes that catalyze the reversible oxidation of various 2-hydroxyacids. Members of this family are involved in metabolic pathways such as the phosphorylated L-serine biosynthesis pathway, where they convert 3-phospho-D-glycerate to 3-phosphonooxypyruvate. Some enzymes also act on 2-hydroxyglutarate, converting it to 2-oxoglutarate. Additionally, certain members are involved in the degradation of L-serine via 3-hydroxypyruvate, reducing it to D-glycerate. Others participate in the (R,S)-sulfolactate degradation pathway, specifically acting on the (S)-enantiomer of 3-sulfolactate and converting sulfopyruvate to sulfolactate. These enzymes are characterized by their specificity for the D-isomer of the substrate and typically require NAD as a cofactor for their dehydrogenase activity.
Malonyl CoA-ACP Transacylase/Polyketide Synthase FabD (Mal-CoA-ACP_Trans/PKS_FabD)
Type: Family

The FabD family is involved in various biosynthetic processes related to fatty acid and polyketide synthesis. Members of this family function as malonyl CoA-acyl carrier protein transacylases, catalyzing the transfer of malonyl groups to acyl-carrier-proteins, which is a critical step in the elongation of fatty acid chains. Some members are specifically involved in the mitochondrial biosynthesis of fatty acids, while others participate in the assembly of complex polyketide structures, such as antibiotics like thailandamide and bacillaene. The family includes proteins with potential acyl transferase and flavin mononucleotide-dependent oxidoreductase activities, indicating a role in secondary metabolism and the synthesis of diverse bioactive compounds.
Class-I pyridoxal-phosphate-dependent aminotransferase-like (Class-I_PLP-dep_aminotransf)
Type: Family

The Class-I Pyridoxal-phosphate-dependent aminotransferase family is involved in a variety of metabolic pathways, catalysing the transfer of amino groups between amino acids and alpha-keto acids. Members of this family exhibit broad substrate specificity, participating in the biosynthesis and degradation of amino acids such as alanine, methionine, and aromatic amino acids like phenylalanine, tyrosine, and tryptophan. They are also implicated in the production of secondary metabolites and can function in the salvage pathways of certain amino acids. Some members regulate the expression of efflux pumps in bacteria and may possess aminotransferase activity. The enzymes typically utilize pyridoxal phosphate as a cofactor and are essential for various cellular processes, including the synthesis of neurotransmitters and the interconversion of amino acids for energy metabolism.
Fe(2+) Transporter FeoB GTPase (FeoB_GTPase)
Type: Family

The FeoB GTPase family is comprised of proteins that function primarily as transporters for the uptake of ferrous iron (Fe(2+)) across the cell inner membrane into the cytoplasm. These transporters are GTP-driven, coupling GTP-binding and hydrolysis to channel opening and Fe(2+) uptake. The GTPase activity involves a guanine nucleotide-binding site that undergoes conformational changes between active GTP-bound and inactive GDP-bound states. This conformational shift is thought to be essential for the function of the transporter, potentially regulating the opening and closing of the channel for iron transport. Some family members may also be involved in manganese uptake rather than iron. The family belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily and plays a crucial role in bacterial iron homeostasis, which is vital for various cellular processes, including growth and survival in iron-restricted environments.
Dihydroxyacetone Kinase (DAK) (Dihydroxyacetone_Kinase)
Type: Family

The Dihydroxyacetone Kinase (DAK) family includes enzymes that catalyze the phosphorylation of dihydroxyacetone and glyceraldehyde. Members of this family are involved in various metabolic pathways, including the degradation of sugars such as L-threitol and erythritol, allowing organisms to utilize these compounds as carbon sources. Some DAK family proteins also have additional functions, such as the triokinase/FMN cyclase, which can split ribonucleoside diphosphate-X compounds, with FAD being the preferred substrate. This activity is known to repress IFIH1-mediated cellular antiviral responses. The family is characterized by the presence of DhaK and DhaL domains, which have distinct roles in enzyme activity. The DhaK domain typically binds dihydroxyacetone, while the DhaL domain is associated with ADP-binding and can display cyclase activity. Regulatory mechanisms within the family include inhibition by substrates of alternate activities and involvement in transcriptional regulation through interactions with transcription factors.
Ribonucleoside diphosphate reductase class-2 (RdRp_reductase_class-2)
Type: Family

The ribonucleoside diphosphate reductase class-2 family is involved in the biosynthesis of deoxyribonucleotides from ribonucleotides, providing the necessary precursors for DNA synthesis. Members of this family are vitamin B12-dependent enzymes that play a crucial role in DNA repair and replication, especially during conditions of oxygen limitation. Some family members are adenosylcobalamin-dependent ribonucleoside-triphosphate reductases, which are allosterically regulated by ATP and dNTP, indicating a sophisticated control mechanism for maintaining deoxyribonucleotide levels in the cell.
Centromere and Transposable Element-Derived Protein (CenT-Element_Derived)
Type: Family

This family of proteins includes members that are involved in centromere and heterochromatin binding, DNA binding, and may play roles in centromere formation, kinetochore assembly, and DNA transposition. Some proteins within this family are known to bind specific DNA sequences, such as the CENP-B box in alphoid satellite DNA, and may organize these sequences into higher-order structures. Others are derived from tigger transposable elements and may retain functions related to transposition. Additionally, certain family members are implicated in biosynthetic pathways, such as the production of chaetoglobosin A, and may perform enzymatic functions like epoxidation, dehydrogenation, and Diels-Alder cyclization. The family also includes proteins that may regulate gene expression, as seen in the control of pyruvate decarboxylase synthesis.
Bacterial PTS System Sugar Transport Components (Bacterial_PTS_Sugar_Transport)
Type: Family

The protein family is involved in the phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS), which is a key carbohydrate active transport system in bacteria. The family includes components that catalyze the phosphorylation of sugar substrates during their translocation across the cell membrane. Specific members of the family are responsible for the transport and phosphorylation of fructose, mannose, and 2-O-alpha-mannosyl-D-glycerate. The system comprises several domains: EIIC forms the translocation channel and binds the substrate; EIIB is phosphorylated on a cysteinyl residue and transfers the phosphoryl group to the sugar; EIIA is phosphorylated on a histidyl residue and transfers the phosphoryl group to EIIB. Some members have a duplicated EIIB domain (EIIB') that facilitates phosphoryl transfer and high-affinity recognition of the diphosphoryl transfer protein (DTP).
BEACH Domain-Containing (BEACH_Domain)
Type: Family

The BEACH domain-containing protein family is involved in a variety of cellular processes, including signal transduction, vesicle trafficking, membrane trafficking, and organelle organization. Members of this family play roles in polarized secretion, phagophore growth during mitophagy, coupling of TNF receptors to sphingomyelinase for ceramide production, and regulation of protein kinase A anchoring. They are also implicated in thrombopoiesis, development of immune effector molecules, and regulation of endosomal and lysosomal trafficking. This includes sorting of endosomal proteins, regulation of lysosome-related organelles, autophagosome maturation, and phagosome maturation in immune cells. Additionally, they may participate in plant effector triggered immunity, negative regulation of lysosome biogenesis, and cell fate determination in various organisms.
Cyclic nucleotide-gated cation channel (CNG_cation_channel)
Type: Family

The Cyclic Nucleotide-Gated Cation Channel family is involved in various signal transduction pathways, primarily in sensory neurons. Members of the family are activated by cyclic nucleotides (cAMP or cGMP), leading to the opening of nonselective cation channels. In visual systems, they play a crucial role in phototransduction by mediating the depolarization of photoreceptors in response to changes in cGMP levels due to light exposure. In olfactory systems, they are essential for odorant signal transduction, where cAMP serves as a second messenger. The channels are also involved in adaptation processes, allowing rapid response to stimuli and extending the range of detection. Some family members are implicated in other cellular functions, such as sperm chemotaxis and maintaining normal axon morphology.
[NiFe]/[NiFeSe] hydrogenase large subunit (NiFe/NiFeSe_hydrgnase_LSU)
Type: Family

The [NiFe]/[NiFeSe] hydrogenase large subunit family includes enzymes that play a crucial role in energy metabolism by catalyzing the reversible oxidoreduction of molecular hydrogen. Members of this family are involved in various physiological processes, such as hydrogen uptake, hydrogen cycling during fermentative growth, and the recycling of hydrogen produced by nitrogenase. This recycling is significant for ATP production and for protecting nitrogenase from oxygen damage under certain conditions. Additionally, some members are part of complexes that reduce methanophenazine to dihydromethanophenazine. The HupK family proteins are associated with hydrogenase expression and formation, suggesting a regulatory role in hydrogenase enzyme systems.
Engulfment and cell motility domain-containing protein (ELMO_domain-containing)
Type: Family

This family of proteins is involved in cellular processes related to the cytoskeleton, including phagocytosis of apoptotic cells and cell motility. Members of this family act in concert with other proteins such as DOCK1 and CRK to facilitate these processes. Some proteins within this family are proposed to activate Rac Rho small GTPases, potentially enhancing the guanine nucleotide exchange factor (GEF) activity of their partners. Additionally, certain members function as GTPase-activating proteins (GAPs) for the ARL2 GTPase and other related factors, but not for GTPases outside the Arf family. This indicates a role in modulating the activity of GTPases involved in various signaling pathways. Furthermore, some proteins in this family are implicated in regulating antiviral responses and maintaining proper cell shape during phagocytosis and chemotaxis by modulating actin polymerization.
Histone-lysine N-methyltransferase (H3K4_H4K5_MeTrfase)
Type: Family

The protein family is characterized by histone-lysine N-methyltransferase activity, with members specifically methylating lysine residues on histones, such as 'Lys-4' of histone H3 and 'Lys-5' of histone H4. These modifications play crucial roles in transcriptional regulation, chromatin organization, and epigenetic signaling. Some family members also methylate non-histone proteins, including p53/TP53 and RB1, influencing their DNA-binding and transcriptional regulation activities. The family is involved in various biological processes, including transcriptional activation, cardiomyocyte differentiation, cardiac morphogenesis, lifespan modulation, and oxidative stress resistance. Members of the family typically interact with HSP90alpha for enhanced activity and are part of the class V-like SAM-binding methyltransferase superfamily.
FAST kinase domain-containing (FAST_kinase)
Type: Family

The FAST kinase family is involved in various aspects of mitochondrial RNA processing and stability, as well as mitochondrial respiration and translation. Members of this family play crucial roles in the biogenesis of mitochondrial-encoded mRNAs, regulating their abundance and half-lives. They are essential for the assembly and activity of mitochondrial respiratory complexes, such as complex I and IV, by stabilizing specific mRNAs like MT-ND3 and MT-CO1. Some members are also implicated in cell cycle progression and may influence mitochondrial apoptosis. Additionally, the RAP domain within these proteins is vital for RNA-binding and is necessary for their function in mRNA stability and translation. The family also includes proteins that regulate chloroplast RNA homeostasis and are involved in chloroplast development and defense responses.
26S Proteasome and COP9 Signalosome Components (26S_Proteasome/COP9_Components)
Type: Family

This family of proteins includes components of the 26S proteasome and the COP9 signalosome. Members involved in the 26S proteasome play a role in the ATP-dependent degradation of ubiquitinated proteins, maintaining protein homeostasis by removing misfolded or damaged proteins and those no longer needed, thus participating in cell cycle progression, apoptosis, and DNA damage repair. They are essential for proteasome assembly and are linked to increased proteasome activity in embryonic stem cells. Other family members are part of the COP9 signalosome complex, which regulates the ubiquitin conjugation pathway by deneddylation of cullin subunits of E3 ligase complexes, altering their activity. This process is involved in various cellular and developmental processes, including photomorphogenesis, neuronal differentiation, and circadian rhythm regulation.
Pentatricopeptide Repeat-containing Protein P Subfamily (PPR_P_subfamily)
Type: Family

The PPR family, specifically the P subfamily, consists of proteins characterized by the presence of pentatricopeptide repeat motifs. These proteins are predominantly involved in post-transcriptional processes within organelles such as mitochondria and chloroplasts. They play crucial roles in the expression and stability of organelle-specific RNAs, including the initiation of translation, RNA editing, splicing, and the stabilization of RNA transcripts. Members of the PPR family are essential for the proper functioning of the mitochondrial electron transport chain and the assembly of thylakoid protein complexes in chloroplasts. They achieve these functions by binding to specific RNA sequences or structures, thereby influencing RNA metabolism and the expression of organelle-encoded genes.
V-ATPase V0D/AC39 subunit (V-ATPase_V0D/AC39_subunit)
Type: Family

The V-ATPase V0D/AC39 subunit family is involved in the synthesis of ATP from ADP utilizing a proton gradient across the membrane. The family includes proteins that are integral components of the V-type ATP synthase complex, which is responsible for ATP production in various cellular membranes. Some members of the family are also involved in ATP-driven sodium extrusion, highlighting a role in ion transport and homeostasis. The family's function is essential for energy conversion and is critical for the survival and function of organisms across different domains of life.

A-type ATPases (archaeal-type ATPases) and V-ATPases, all included in this entry, are thought to have evolved from common ancestral genes .
Diverse function phospholipase D-related protein (Diverse_PLD-related)
Type: Family

This family of proteins includes enzymes with diverse functions, such as hydrolyzing membrane phospholipids to generate signaling molecules, acting as 5'-3' exonucleases involved in nucleic acid degradation and inflammatory response regulation, and participating in viral processes like envelope formation and cell-to-cell spread. Some members exhibit broad lipase activity, including phospholipase C, A, and triacylglycerol lipase activities. Others are involved in lysosomal homeostasis, endosomal protein sorting, and myotube formation. Additionally, certain viral proteins in this family contain late-budding domains that interact with the host's ESCRT machinery for viral particle budding.
Troponin I (Troponin_I)
Type: Family

The Troponin I family consists of inhibitory subunits of the troponin complex, which is a critical component of the thin filament regulatory system in striated muscles. These proteins confer calcium-sensitivity to the actomyosin ATPase activity, which is essential for muscle contraction and relaxation. Members of this family are involved in the development and maintenance of muscle and the nervous system, and may also play a role in the cytoskeletal apparatus. The family includes isoforms specific to cardiac, fast skeletal, and slow skeletal muscles, reflecting their specialized roles in different muscle tissue types.
IgLON domain-containing protein (IgLON_domain)
Type: Family

This family of proteins is involved in neural development and function, including neuronal growth, axon targeting, and cell adhesion. Members of this family are thought to mediate selective growth of neuronal connections and contribute to the guidance of developing axons as well as the remodeling of mature circuits, particularly within the limbic system. Some proteins in this family are implicated in inhibiting neurite outgrowth, while others may function as neural cell adhesion molecules or be involved in opioid binding in the presence of acidic lipids. Additionally, certain members may play roles in cortical neuron migration, learning, memory performance, and cell-cell interactions.