SII-SWORD/CoKE huggingface dataset:
Kelch-like protein 15, BACK domain (KLHL15_BACK)
Type: Domain

The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding , while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins . In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins . Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases .

Kelch-like protein 15 (KLHL15) is a substrate-specific adaptor for the Cullin3 E3 ubiquitin-protein ligase complex that targets the serine/threonine-protein phosphatase 2A (PP2A) subunit PPP2R5B for ubiquitination and subsequent proteasomal degradation, thus promoting exchange with other regulatory subunits . It also plays a key role in DNA damage response, favoring DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR), by targeting the DNA-end resection factor RBBP8/CtIP for ubiquitination and subsequent proteasomal degradation. KLHL15 contains a BTB domain and kelch repeats, characteristics of a kelch family protein .

This entry represents the BACK domain of KLHL15.
Glycine receptor subunit beta, extracellular domain (GlyR_beta__ECD)
Type: Domain

Glycine receptors (GlyR) are ligand-gated chloride channels that function as major inhibitory neurotransmitters (NT) in the adult vertebrate central nervous system (CNS). Glycinergic synapses have a well-established role in the processing of motor and sensory information that controls
movement, vision and audition . Strychnine acts as a competitive antagonist of glycine binding, thereby reducing the activity of inhibitory neurons. Whilst glycine is the principal physiological agonist at GlyRs, taurine and beta-alanine also behave as agonists .

This entry represents the extracellular domain (ECD) of the beta subunit of GlyR.
Gamma-aminobutyric acid receptor subunit pi, transmembrane domain (GABAAR_pi_TM)
Type: Domain

Type-A gamma-aminobutyric acid receptor (GABAAR) is an anionic channel, mediating fast inhibitory synaptic transmission. The Pi subunit of GABAAR is expressed mainly in non-neuronal tissues such as the mammary gland, prostate gland, lung, thymus, and uterus. It is also highly expressed in certain types of cancer such as basal-like breast cancer and pancreatic ductal adenocarcinoma . It has been suggested that polymorphisms in its gene may be associated with the susceptibility to systemic lupus erythematosus (SLE) .

This entry represents the transmembrane (TM) domain of the pi subunit of GABAAR, which consists of four transmembrane-spanning α-helical segments that are linked by loops.
Glucagon-like peptide-1 receptor, 7TM (GLP1R_7TM)
Type: Domain

Glucagon-like peptide-1 (GLP-1), which is encoded by the glucagon gene and released from the gut in response to nutrients, is a potent stimulator of glucose-induced insulin secretion and proinsulin gene expression of pancreatic beta-cells . GLP1R is activated by glucagon-like peptide 1 (GLP1), which is derived from the large proglucagon precursor. Activation of GLP1R stimulates glucose-dependent insulin secretion from pancreatic beta cells. In humans, GLP-I exerts its physiological effect as an incretin. Patients with insulinoma tumors show uncontrolled insulin hypersecretion . The GLP-I receptor binds GLP-1 with high affinity and couples to activation of adenylate cyclase . The receptor specifically binds GLP-1 and not peptides of related structure and function, such as glucagon, gastric inhibitory peptide, VIP or secretin . It is thought that GLP-I might have effects beyond the pancreas, including the cardiovascular and central nervous systems, where a receptor with the same ligand-binding specificity is found .

This entry represents the transmembrane domain of GLP1R which contains a binding pocket for negative allosteric modulators. According to molecular modelling and mutagenesis studies, agonist positive allosteric modulators may target the same region , which may be useful for type 2 diabetes therapies development.
Glyoxylate carboligase, TPP-binding domain (Gcl_TPP-bd)
Type: Domain

Glyoxylate carboligase (Gcl), also called tartronate-semialdehyde synthase, releases CO2 while synthesizing a single molecule of tartronate semialdehyde from two molecules of glyoxylate. Its activity depends on the presence of thiamine diphosphate (ThDP), a derivative of vitamin B1 . In the D-glycerate pathway, part of allantoin degradation in the Enterobacteriaceae, tartronate semialdehyde is converted to D-glycerate and then 3-phosphoglycerate, a product of glycolysis and entry point in the general metabolism.

This entry represents the TPP-binding module of Gcl, found at the C-terminal end.
Vasoactive intestinal polypeptide receptor 2, 7TM (VIP-R2_7TM)
Type: Domain

Vasoactive intestinal peptide (VIP) receptor 2 is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include secretin, growth-hormone-releasing hormone (GHRH), and pituitary adenylate cyclase activating polypeptide (PACAP). These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. VIP and PACAP exert their effects through three G protein-coupled receptors, PACAP-R1, VIP-R1 (vasoactive intestinal receptor type 1, also known as VPAC1) and VIP-R2 (or VPAC2). VIP-R1 and -R2 specifically bind and respond to both VIP and PACAP. VIP and PACAP and their receptors are widely expressed in the brain and periphery. They are upregulated in neurons and immune cells in responses to CNS injury and/or inflammation and exert potent anti-inflammatory effects, as well as play important roles in the control of circadian rhythms and stress responses, among many others .

This entry represents the transmembrane domain of VIP-R2.
Elongation factor 3, four helical bundle domain superfamily (EF3_4HB_sf)
Type: Homologous_superfamily

This entry represents a domain found in elongation factor 3A where it packs against the bottom of the concave face of the HEAT domain .
Secretin receptor, 7TM (Secretin_7TM)
Type: Domain

The secretin-like GPCRs include secretin , calcitonin , parathyroid hormone/parathyroid hormone-related peptides and vasoactive intestinal peptide , all of which activate adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. These receptors contain seven transmembrane regions, in a manner reminiscent of the rhodopsins and other receptors believed to interact with G-proteins (however there is no significant sequence identity between these families, the secretin-like receptors thus bear their own unique '7TM' signature). Their N-terminal is probably located on the extracellular side of the membrane and potentially glycosylated. This N-terminal region contains a long conserved region which allows the binding of large peptidic ligand such as glucagon, secretin, VIP and PACAP; this region contains five conserved cysteines residues which could be involved in disulphide bond. The C-terminal region of these receptor is probably cytoplasmic. Every receptor gene in this family is encoded on multiple exons, and several of these genes are alternatively spliced to yield functionally distinct products.

Secretin is a polypeptide secreted by entero-endocrine S cells in the small intestine, is involved in maintaining body fluid balance. This polypeptide regulates the secretion of bile and bicarbonate into the duodenum from the pancreatic and biliary ducts, as well as regulates the duodenal pH by the control of gastric acid secretion . In addition to regulating the pH of the duodenal content, secretin plays a central role in diet induced thermogenesis: acts as a non-sympathetic brown fat (BAT) activator mediating prandial thermogenesis, which consequently induces satiation . Studies with secretin receptor-null mice indicate that secretin plays a role in regulating renal water reabsorption. Secretin mediates its biological actions by elevating intracellular cAMP via G protein-coupled secretin receptor, which is expressed in the brain, pancreas, stomach, kidney, and liver .

This entry represents the transmembrane domain of secretin receptor.
Elongation Factor 3, chromodomain-like insertion superfamily (eEF3_chromodomain-like_sf)
Type: Homologous_superfamily

This entry includes members of the EF3 (Elongation Factor 3) family, which contain the ABC transporter domains and belong to the family of ABC (ATP-binding cassette) proteins. Yef3 (elongation factor 3A) and Hef3 (elongation factor 3B) are included in this entry.

The ribosomal elongation cycle requires two elongation factors: elongation factor 1 alpha (EF-1 alpha), which mediates the binding of an aminoacyl-tRNA to the ribosomal A site, and elongation factor 2 (EF-2), which catalyses the translocation reaction. In yeasts and other higher fungi, a third elongation factor, EF-3 is essential. EF-3 (also known as Yef3 in budding yeast) is required for the binding of the aminoacyl-tRNA-eEF1A-GTP ternary complex to the ribosomal A-site . EF-3 consists of an N-terminal HEAT repeat domain, followed by a four-helix bundle and two ABC-type ATPase domains, with a chromodomain inserted in ABC2 . The binding of EF-3 to ribosome may allow tRNA release . Hef3 is a weakly expressed functional homologue of YEF3.

This entry represents the chromodomain-like insertion in the ABC2 domain of eEF3, which is critical to eEF3 function .
AMP nucleosidase, phosphorylase domain (AMN_phosphorylase)
Type: Domain

AMP nucleosidase (AMN) catalyses the hydrolysis of AMP to form adenine and ribose 5-phosphate. It is only found in prokaryotes, where it plays a role in purine nucleoside salvage and intracellular AMP level regulation . The gene for AMP nucleosidase from Escherichia coli (amn) encodes a protein of 483 amino acids. A comparison of the amino acid sequence for AMP nucleosidase with that for yeast AMP deaminase shows that there is a region where only six out of eight amino acids are identical but there is no other overall homology. AMN also showed little similarity to consensus sequences for adenylate binding sites even though the enzyme is known to have a catalytic site for AMP and regulatory sites for MgATP and phosphate .

This entry represents the phosphorylase domain from AMP nucleosidase.
Flagellar biosynthesis protein FlhF, GTPase domain (FlhF__GTPase_dom)
Type: Domain

This entry represents the GTPase domain found at the C-terminal of flagellar biosynthetic protein FlhF. The assembly of flagella is a multi-step process and relies on a complex type III export machinery located in the cytoplasmic membrane. The FlhF protein is a essential for the placement and assembly of polar flagella and has been classified as a signal-recognition particle (SRP)-type GTPase . It is similar to the 54 kd subunit (SRP54) of the SRP that mediates the transport to or across the plasma membrane in bacteria and the endoplasmic reticulum in eukaryotes . SRP recognises N-terminal signal sequences of newly synthesized polypeptides at the ribosome. The SRP-polypeptide complex is then targeted to the membrane by an interaction between SRP and its cognate receptor (SR). FlhF activities and the net effect of FlhF on flagellation phenotypes appear to be different among polar flagellates .
GTP-binding protein BipA, GTP-binding domain (BipA_GTP-bd_dom)
Type: Domain

This entry includes the GTP-binding protein BipA or TypA (Tyrosine phosphorylated protein A (TypA), also known as 50S ribosomal subunit assembly factor BipA) from bacteria and its homologue from Arabidopsis (putative elongation factor TypA-like SVR3). BipA is a 50S ribosomal subunit assembly protein with GTPase activity, required for 50S subunit assembly at low temperatures. It also functions as a translation factor that is required specifically for the expression of the transcriptional modulator Fis. BipA binds the 70S ribosome at a site that coincides with that of EF-G and has a GTPase activity that is sensitive to high GDP:GTP ratios and is stimulated by 70S ribosomes programmed with mRNA and aminoacylated tRNAs . The growth rate-dependent induction of BipA allows the efficient expression of Fis, thereby modulating a range of downstream processes, including DNA metabolism and type III secretion. This GTPase impacts interactions between enteropathogenic E.coli (EPEC) and epithelial cells and also has an effect on motility . It appears to be involved in the regulation of several processes important for infection, including rearrangements of the cytoskeleton of the host, bacterial resistance to host defense peptides, flagellum-mediated cell motility, and expression of K5 capsular genes .

TypA-like SVR3 is a putative chloroplastic elongation factor involved in response to chilling stress. It is required for proper chloroplast rRNA processing and/or translation at low temperature and it is also involved in plastid protein homeostasis .

This entry represents the GTP-binding domain.
GTP-binding protein BipA, domain 2 (BipA_II)
Type: Domain

BipA (also called TypA) is a highly conserved protein with global regulatory properties in Escherichia coli. Mutants show altered regulation of some pathways. BipA is a 50S ribosomal subunit assembly protein with GTPase activity, required for 50S subunit assembly at low temperatures and it also functions as a translation factor that is required specifically for the expression of the transcriptional modulator Fis. BipA binds to ribosomes at a site that coincides with that of EF-G and has a GTPase activity that is sensitive to high GDP:GTP ratios and is stimulated by 70S ribosomes programmed with mRNA and aminoacylated tRNAs . The growth rate-dependent induction of BipA allows the efficient expression of Fis, thereby modulating a range of downstream processes, including DNA metabolism and type III secretion. This GTPase impacts interactions between enteropathogenic E.coli (EPEC) and epithelial cells and also has an effect on motility . It appears to be involved in the regulation of several processes important for infection, including rearrangements of the cytoskeleton of the host, bacterial resistance to host defence peptides, flagellum-mediated cell motility, and expression of K5 capsular genes .

This entry also includes TypA-like SVR3 from Arabidopsis, a putative chloroplastic elongation factor involved in response to chilling stress. It is required for proper chloroplast rRNA processing and/or translation at low temperature and it is also involved in plastid protein homeostasis .

This entry represents domain II of BipA/TypA, which shows similarity to the domain II of the elongation factors (EFs) EF-G and EF-Tu .
GTP-binding protein BipA, domain 3 (BipA_III)
Type: Domain

BipA (also called TypA) is a highly conserved protein with global regulatory properties in Escherichia coli. Mutants show altered regulation of some pathways. BipA is a 50S ribosomal subunit assembly protein with GTPase activity, required for 50S subunit assembly at low temperatures and it also functions as a translation factor that is required specifically for the expression of the transcriptional modulator Fis. BipA binds to ribosomes at a site that coincides with that of EF-G and has a GTPase activity that is sensitive to high GDP:GTP ratios and is stimulated by 70S ribosomes programmed with mRNA and aminoacylated tRNAs . The growth rate-dependent induction of BipA allows the efficient expression of Fis, thereby modulating a range of downstream processes, including DNA metabolism and type III secretion. This GTPase impacts interactions between enteropathogenic E.coli (EPEC) and epithelial cells and also has an effect on motility . It appears to be involved in the regulation of several processes important for infection, including rearrangements of the cytoskeleton of the host, bacterial resistance to host defence peptides, flagellum-mediated cell motility, and expression of K5 capsular genes .

This entry also includes TypA-like SVR3 from Arabidopsis, a putative chloroplastic elongation factor involved in response to chilling stress. It is required for proper chloroplast rRNA processing and/or translation at low temperature and it is also involved in plastid protein homeostasis .

This entry represents domain III of BipA/TypA, which adopts an α/β structure.
RNA-binding protein 47, RNA recognition motif 1 (RBM47_RRM1)
Type: Domain

RBM47 is a putative RNA-binding protein that shows high sequence homology with heterogeneous nuclear ribonucleoprotein R (hnRNP R) and heterogeneous nuclear ribonucleoprotein Q (hnRNP Q). Like hnRNP R and hnRNP Q, RBM47 contains two well-defined and one degenerated RNA recognition motifs (RRMs). RBM47 is necessary for Cytidine to Uridine RNA editing .

This entry represents the RNA recognition motif 1 (RRM1) of RBM47.
Cobyric acid synthase, N-terminal domain (CobQ_N)
Type: Domain

Cobyric acid synthase (CobQ) plays a role in the cobalamin (vitamin B12) biosynthesis pathway. This enzyme catalyses amidations at positions B, D, E, and G on adenosylcobyrinic A,C-diamide in the biosynthesis of cobalamin. NH(2) groups are provided by glutamine, and one molecule of ATP is hydrogenolysed for each amidation .

This entry represents the N-terminal domain of CobQ.
NTP pyrophosphohydrolase MazG-related, YpjD/YvdC (YpjD/YvdC)
Type: Family

This family represents a group of distantly related to MazG-type NTP pyrophosphohydrolase (NTP-PPase) which contain the conserved residues of the MazG domain (at least three of the Glu residues, Asp, Lys and Arg), including those shown to be functionally important . This entry includes the putative pyrophosphatases YpjD and YvdC from Bacillus subtilis. Although its biological role has not been described in detail, YpjD shows significant sequence similarity to the dimeric 2-deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTP pyrophosphatase or dUTPase) and NTP-PPase MazG proteins. However, unlike typical tandem-domain MazG proteins, BsYpjD contains a single MazG-like domain .
Glutathione S-transferases Omega-like, C-terminal (GST_Omega-like_C)
Type: Domain

This entry represents the C-terminal domain of Saccharomyces cerevisiae glutathione S-transferase (GST) Omega-like subfamily, which is composed of three Saccharomyces cerevisiae GST omega-like (Gto) proteins, Gto1p, Gto2p (also known as Extracellular mutant protein 4 or ECM4p), and Gto3p. This domain is also found in glutathionyl-hydroquinone reductases YqjG and PcpF from bacteria which are closely related to the Omega-class of GSTs . The three Saccharomyces cerevisiae Gto proteins are omega-class GSTs with low or no GST activity against standard substrates, but have glutaredoxin/thiol oxidoreductase and dehydroascorbate reductase activity through a single cysteine residue in the active site . Gto1p is located in the peroxisomes while Gto2p and Gto3p are cytosolic . The gene encoding Gto2p, called ECM4, is involved in cell surface biosynthesis and architecture. S. cerevisiae ECM4 mutants show increased amounts of the cell wall hexose, N-acetylglucosamine. More recently, global gene expression analysis shows that ECM4 is upregulated during genotoxic conditions and together with the expression profiles of 18 other genes could potentially differentiate between genotoxic and cytotoxic insults in yeast .
16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA (TlyA)
Type: Family

This family represents the TlyA family of proteins which includes 16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA, Hemolysin A and related proteins.

Haemolysins are exotoxins that attack blood cell membranes and cause cell rupture. The mechanism of action is not well defined. Hemolysin A is induced by sodium ribonucleate, and is produced by pathogenic bacterial strains. Hemolysin A from Treponema hyodysenteriae causes swine dysentery .

16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA catalyses the 2'-O-methylation at nucleotides C1409 in 16S rRNA and C1920 in 23S rRNA . It is involved in virulence by promoting adherence and invasion to host cells . In M. tuberculosis, it acts as a host evasion factor, that significantly contributes to the pathogenesis of M.tuberculosis by modulating adaptive immune responses by inhibiting host-protective Th1 and Th17 cytokine responses as well as autophagy . In Campylobacter jejuni, has been shown to be involved in susceptibility to antibiotic capreomycin . Additionally, TlyA may be involved in ribosomal biogenesis and assembly . TlyA also exhibits haemolytic activity in vitro, by binding with and forming oligomers into host cell membranes .
NusG, N-terminal (NGN)
Type: Domain

The N-Utilization Substance G (NusG) protein is involved in transcription elongation and termination in bacteria. NusG is essential in Escherichia coli and associates with RNA polymerase elongation and Rho-termination. Homologs of the NusG gene exist in all bacteria. The NusG N-terminal domain (NGN) is similar in all NusG homologs, but its C-terminal domain and the linker that separates these two domains are different. The domain organization of NusG suggests that the common properties of NusG and its homologs are due to their similar NGN domains .