SII-SWORD/CoKE huggingface dataset:
Septin-type guanine nucleotide-binding (G) domain (G_SEPTIN_dom)
Type: Domain

The P-loop guanosine triphosphatases (GTPases) control a multitude of biological processes, ranging from cell division, cell cycling, and signal transduction, to ribosome assembly and protein synthesis. GTPases exert their control by interchanging between an inactive GDP-bound state and an active GTP-bound state, thereby acting as molecular switches. The common denominator of GTPases is the highly conserved guanine nucleotide-binding (G) domain that is responsible for binding and hydrolysis of guanine nucleotides.

Septins are a family of eukaryotic cytoskeletal proteins conserved from yeasts to humans. The septin family belongs to the guanosine-triphosphate (GTP)ase superclass of P-loop nucleoside triphosphate (NTP)ases. Septins participate in diverse cellular functions including cytokinesis, vesicle trafficking, vesicle fusion, axonal guidance and migration, diffusion barrier, scaffolds, pathogenesis and others. Septin monomers form homo- and hetero-oligomeric complexes that assemble into filaments. Structurally all septins have a GTP-binding domain flanked by N- and C-terminal regions of variable length. The GTP-binding domain is the most highly conserved and is characterised by the presence of three of the five classical GTP-binding motifs. The G1 motif (or Walker A box, GxxxxGKS/T) forms the P-loop, which interacts directly with the nucleotide, whereas the G3 (DxxG) and G4 (xKxD) motifs are respectively essential for Mg(2+) binding and for conferring GTP binding specificity over other nucleotides. The basic structure of the septin-type G domain closely resembles the canonical G domain exemplified by Ras, with six β-strands and five α-helices. A unique feature of the septin-type G domain is the presence of four additional elements compared to Ras. These are the helix alpha5' between alpha4 and beta6, the two antiparallel strands beta7 and beta8, and the alpha6 C-terminal helix that points away from the G domain at a 90deg angle relative to the axis of interaction between subunits .

This entry represents the septin-type G domain.
SAM-dependent methyltransferase DRM (SAM_MeTfrase_DRM)
Type: Domain

Domains Rearranged Methylases (DRM1 and DRM2) are de novo cytosine methyltransferases from plants involved in the initial methylation of unmethylated DNA sequences . Plant DNA is frequently methylated in three different sequence contexts: CG, CHG, and CHH (H = A, T, or C). In Arabidopsis thaliana, the maintenance of CHH methylation is controlled by DRM2 .

This entry represents the methyltransferase domain of DRM. The overall structure retains a classic class I methyltransferase fold .
Dynamin-type guanine nucleotide-binding (G) domain (G_DYNAMIN_dom)
Type: Domain

This entry represents the dynamin-type guanine nucleotide-binding (G) domain.
SAM-dependent methyltransferase TRM5/TYW2-type (MeTrfase_TRM5/TYW2)
Type: Domain

This entry represents a domain found in the Trm5/Tyw2-type methyltransferase. Trm5 and Tyw2 are S-adenosylmethionine-dependent methyltransferases involved in tRNA methylation .
Very large inducible GTPASE (VLIG)-type guanine nucleotide-binding (G) domain (G_VLIG_dom)
Type: Domain

This is the VLIG-type GTPase domain found in the human Up-regulator of cell proliferation (URGCP), Interferon-induced very large GTPase 1 (GVINP1) and related proteins. URGCP may be involved in cell cycle progression through the regulation of cyclin D1 expression. This protein is thought to play an important role in development of gastric cancer . GVINP1 is a member of the very large inducible GTPases family, which are strongly induced by interferons. GVINP1 contributes to cell-autonomous resistance against pathogens, including bacteria, viruses, and protozoa .

The P-loop guanosine triphosphatases (GTPases) control a multitude of biological processes, ranging from cell division, cell cycling, and signal transduction, to ribosome assembly and protein synthesis. GTPases exert their control by interchanging between an inactive GDP-bound state and an active GTP-bound state, thereby acting as molecular switches. The common denominator of GTPases is the highly conserved guanine nucleotide-binding (G) domain that is responsible for binding and hydrolysis of guanine nucleotides.

The very large inducible GTPase (VLIG) family contributes to the cellular response to both type I and type II interferons (IFNs). Phylogenetically, the VLIG family is relatively old, since there are representatives in zebrafish and salmon. The potential GTP-binding activity of mouse VLIG-1, the prototype VLIG, possesses a classical GTP-binding sequence motif. The G1 or P-loop (G- x(4)-G-K-S) and G3 (D-x(2)-G) motifs are both present in a canonical form. The G4 motif ([NT]-K-x-D), associated in canonical GTPases with contact to the guanine base, is not immediately apparent .
SAM-dependent methyltransferase SMT-type (MeTrfase_SMT)
Type: Domain

Sterol 24-C-methyltransferase Erg6 from fission yeast catalyses the methyl transfer from S-adenosyl-methionine (SAM) to the C-24 of zymosterol to form fecosterol. It is involved in the biosynthesis of ergosterol, which is important for plasma membrane structure and function . Arabidopsis contains three sterol methyltransferases (SMT1, SMT2, and SMT3) homologous to yeast Erg6 .

This entry represents a domain found in the Erg6/SMT (S-adenosyl-L-methionine (SAM):C-24 sterol methyl transferase) proteins.
IRG-type guanine nucleotide-binding (G) domain (G_IRG_dom)
Type: Domain

The P-loop guanosine triphosphatases (GTPases) control a multitude of biological processes, ranging from cell division, cell cycling, and signal transduction, to ribosome assembly and protein synthesis. GTPases exert their control by interchanging between an inactive GDP-bound state and an active GTP-bound state, thereby acting as molecular switches. The common denominator of GTPases is the highly conserved guanine nucleotide-binding (G) domain that is responsible for binding and hydrolysis of guanine nucleotides.

The p47 or immunity-related GTPases (IRG) are at least as old as the vertebrates. The IRG proteins are an essential resistance system for immunity against pathogens that enter the cell via a vacuole. They act as a dynamin-like proteins that bind to intracellular membranes and promotes remodeling and trafficking of those membranes . These proteins are required for clearance of acute protozoan and bacterial infections by interacting with autophagy and lysosome regulatory proteins, thereby promoting the fusion of phagosomes with lysosomes for efficient degradation of cargo including microbes . The IRG proteins appear to be accompanied phylogenetically by homologous proteins, named 'quasi IRG' (IRGQ) proteins, that probably lack nucleotide binding or hydrolysis function, and that may form regulatory heterodimers with functional IRG proteins. The region of lowest similarity is in the G domain, and conserved GTP-binding motifs are lacking .
GB1/RHD3-type guanine nucleotide-binding (G) domain (G_GB1_RHD3_dom)
Type: Domain

The P-loop guanosine triphosphatases (GTPases) control a multitude of biological processes, ranging from cell division, cell cycling, and signal transduction, to ribosome assembly and protein synthesis. GTPases exert their control by interchanging between an inactive GDP-bound state and an active GTP-bound state, thereby acting as molecular switches. The common denominator of GTPases is the highly conserved guanine nucleotide-binding (G) domain that is responsible for binding and hydrolysis of guanine nucleotides.

The GB1/RHD3 GTPase family contains a large G domain (~230 amino acids). It is widespread in eukaryotes, but not detectable in bacteria or archaea. One conserved subfamily is typified by the Arabidopsis protein root hair defective 3 (RHD3), whose othologs are present in all crown group eukaryotes. The other subfamily is typified by the interferon gamma-induced antiviral GB1 protein that is conserved in animals. The other GTPases of this subfamily are the brain finger proteins (BFPs), in which the GTPase domain is combined with an N-terminal RING finger domain, which implicates these proteins in ubiquitin-mediated signaling. Most members of this family have a large C-terminal, α-helical extension that probably participates in protein-protein interactions. The GB1/RHD3-type G domain has a low intrinsic affinity for nucleotide and often depends on nucleotide-dependent homodimerization to facilitate GTP hydrolysis .

The large GB1/RHD3-type G domain consists of a six-stranded β-sheet surrounded by eight helices. It contains the conserved sequence elements of GTP-binding proteins with modifications .
Bms1/Tsr1-type G domain (G_Bms1/Tsr1_dom)
Type: Domain

Bms1p and Tsr1p represent a new family of factors required for ribosome biogenesis. They are each independently required for 40S ribosomal subunit biogenesis. Bms1p, a protein required for pre-rRNA processing, contains an evolutionarily conserved guanine nucleotide-binding (G) domain with five conserved polypeptide loops designated G1 through G5, which form contact sites with the guanine nucleotide or coordinate the Mg(2+) ion. Sequences resembling G1 (consensus [GA]-x(4)-G-K-[ST]; also known as a P-loop), G4 (consensus [NT]-K-x-D), and G5 (consensus S-[AG] are present in all Bms1 proteins, and either fully conform with the consensus or contain, at most, single conservative substitutions. The G2 motif (consensus G-P-[IV]-T) contains a T residue involved in the coordination of the Mg(2+) required for GTP hydrolysis. The G3 motif diverges from the consensus found in G proteins, D-x(2)-G; however, the D residue is replaced with the conserved E residue. In contrast, Tsr1p lacks a P-loop and is not predicted to bind GTP. It functions at a later step of 40S ribosome production, possibly in assembly and/or export of 43S pre-ribosomal subunits to the cytosol .

This entry represents a domain found in Bms1 and Tsr1, and includes cases, such as Tsr1, where it may not function as a guanine nucleotide-binding domain.
Era-type guanine nucleotide-binding (G) domain (G_ERA_dom)
Type: Domain

Era (E. coli Ras-like protein) is a small G-protein widely conserved in eubacteria and eukaryotes. It is essential for bacterial cell viability and is required for the maturation of 16S rRNA and assembly of the 30S ribosomal subunit . Era couples cell growth with cytokinesis and plays a role in cell division and energy metabolism. Era contains an N-terminal GTPase domain and a C-terminal distinct derivative of the type-II RNA-binding KH domain . Both domains are important for Era function. Era is functionally able to compensate for deletion of RbfA, a cold-shock adaptation protein that is required for efficient processing of the 16S rRNA.

The Era-type GTPase domain consists of a central six-stranded β-sheet flanked by five α-helices, in which the GTP-binding site is located. Guanine nucleotide molecules interact with highly conserved G protein regions G1-G5 .
FeoB-type guanine nucleotide-binding (G) domain (G_FEOB_dom)
Type: Domain

The P-loop guanosine triphosphatases (GTPases) control a multitude of biological processes, ranging from cell division, cell cycling, and signal transduction, to ribosome assembly and protein synthesis. GTPases exert their control by interchanging between an inactive GDP-bound state and an active GTP-bound state, thereby acting as molecular switches. The common denominator of GTPases is the highly conserved guanine nucleotide-binding (G) domain that is responsible for binding and hydrolysis of guanine nucleotides.

The FeoB family of GTPases is widespread, although not ubiquitous, in Bacteria and Archaea, but missing from Eukaryota. FeoB is involved in the uptake of ferrous iron (Fe(2+)), an important cofactor in biological electron transfer and catalysis. Most of the FeoB proteins contain an N-terminal G-domain, connected by an entirely α-helical linker peptide to the membrane domain with 8 to 12 predicted membrane-spanning α-helices, while in some organisms the G-domain is expressed separately as a soluble protein. The FeoB- type G domain belongs to the TrmE-Era-EngA-EngB-Septin-like (TEES) superfamily of the TRAFAC class GTPases.

The structure of the FeoB-type G domain follows the typical fold of small GTP- binding proteins, consisting of a seven-stranded β-sheet surrounded by five α-helices. The ~170-residue FeoB-type G domain harbours five short amino-acid motifs (G1-G5) that are critical in the binding of both a magnesium (Mg(2+)) ion and the guanine nucleotide. The G1 motif (GxxxxGKS/T) (P-loop) is in position to stabilise the beta- and gamma-phosphates of GTP by hydrogen bonds donated by main-chain amides. The threonine of the G2 motif (P/AGxT) coordinates the Mg(2+). The G3 motif (DxxG) interacts with the Mg(2+) and an oxygen of the gamma-phosphate. The G4 motif (NxxD) is involved in recognition of the guanine nucleotide by forming hydrogen bonds to the guanine base. The G5 motif (S/VSTV]) is, despite low sequence conservation, attributed to critical guanine base coordination .
RNA methyltransferase TrmA, active site (MeTrfase_TrmA_AS)
Type: Active_site

In Escherichia coli, the trmA protein is a tRNA (uracil-5-)-methyltransferase (

) that catalyses the S-adenosylmethionine dependent methylation of U54 in all tRNAs. Orthologues of trmA are found in many eubacterial species. A number of uncharacterised homologues of trmA have been found :

Escherichia coli hypothetical protein ygcA and HI0333, the corresponding Haemophilus influenzae protein.

Haemophilus influenzae hypothetical protein HI0958.

Chlamydia trachomatis protein HOM1.

Fission yeast hypothetical protein SpAC4G8.07c.

It is probable that ygcA/HI0333 and HI0958 are responsible for the methylation of U747 and U1939 in 23S rRNA. In trmA, a cysteine is known to participate in the catalytic mechanism by forming a covalent adduct to C6 of uracil.

This entry represents a conserved region that includes the active site cysteine.
RNA methyltransferase TrmA, conserved site (MeTrfase_TrmA_CS)
Type: Conserved_site

In Escherichia coli, the trmA protein is a tRNA (uracil-5-)-methyltransferase (

) that catalyses the S-adenosylmethionine dependent methylation of U54 in all tRNAs. Orthologues of trmA are found in many eubacterial species. A number of uncharacterised homologues of trmA have been found :

Escherichia coli hypothetical protein ygcA and HI0333, the corresponding Haemophilus influenzae protein.

Haemophilus influenzae hypothetical protein HI0958.

Chlamydia trachomatis protein HOM1.

Fission yeast hypothetical protein SpAC4G8.07c.

It is probable that ygcA/HI0333 and HI0958 are responsible for the methylation of U747 and U1939 in 23S rRNA. In trmA, a cysteine is known to participate in the catalytic mechanism by forming a covalent adduct to C6 of uracil.

This entry represents a conserved site located at the C-terminal end. It contains a conserved histidine.
Intramolecular chaperone auto-processing domain (S74_ICA)
Type: Domain

The Intramolecular Chaperone Auto-processing (ICA) domain, also called Intramolecuar Chaperone Domain (ICD) or C-terminal Intramolecular Chaperone Domain (CIMCD) , is capable of catalysing trimerisation-dependent auto-proteolysis. The ICA domain contains two absolutely conserved serine and lysine residues. They form a catalytic dyad that mediates cleavage at the serine residue. The correct positioning of these catalytic residues, along with an arginine residue that stabilises the oxyanion during the peptide bond breakage, is thought to be achieved only upon folding and trimerisation, enabling the ICA domain to function as a folding sensor. The ICA domain belongs to peptidase family S74.

The ICA domain displays an α1-β1-α2-β2-α3-β3-β4-α4 fold. The ICA domain homotrimer has a jellyfish-like outline with a central threefold symmetry axis and mainly consists of α-helices. It comprises a quite globular core and an extended loop region, reminiscent of
tentacles, protruding from the centre. The central part of the core is a slightly twisted three helix bundle, forming the trimerisation interface .

Some proteins known to contain an ICA domain are listed below:

Animal myelin regulatory factor (MYRF), a key transcriptional regulator for of oligodendrocyte differentiation and central nervous system (CNS) myelination. The MYRF protein undergoes an activating cleavage event to release the functional transcription factor from the transmembrane domain that otherwise anchors it to the endoplasmic reticulum .

Tailed bacteriophage (Caudovirus) endosialidases, the tailspike proteins essential for bacteriophages to infect bacteria encapsulated with polysaccharides .
EngB-type guanine nucleotide-binding (G) domain (G_ENGB_dom)
Type: Domain

This entry represents the EngB-type G domain.

The P-loop guanosine triphosphatases (GTPases) control a multitude of biological processes, ranging from cell division, cell cycling, and signal transduction, to ribosome assembly and protein synthesis. GTPases exert their control by interchanging between an inactive GDP-bound state and an active GTP-bound state, thereby acting as molecular switches. The common denominator of GTPases is the highly conserved guanine nucleotide-binding (G) domain that is responsible for binding and hydrolysis of guanine nucleotides.

Within the translation factor-related (TRAFAC) class of P-loop GTPases, the EngB-type is widespread, but not ubiquitous in all three superkingdoms (missing, for example, from the Crenarchaeota, Caenorhabditis, and Drosophila). Proteins of the EngB-type GTPase family are involved in the biogenesis of ribosomes and are essential for the survival of a wide range of bacteria .

The EngB-type GTPase is comprised of a central β-sheet flanked by alpha- helices, in which semi-conserved residues involved in nucleotide binding are located in five motifs, called G1-G5. The G1 region (GxxxxGKS) forms the P-loop that is responsible for binding the phosphate groups of the guanine nucleotide. The G2 region corresponds to the switch I loop, which contains the consensus motif PGxT. The invariant threonine residue is responsible for binding a magnesium ion required for catalysis. The G3 region corresponds to the Walker B motif (DxxG), which forms part of switch II. The G4 (TKxD) and G5 motifs are involved in interactions with the guanine moiety of the substrate .
HflX-type guanine nucleotide-binding (G) domain (G_HFLX_dom)
Type: Domain

This entry represents the HflX-type G domain.

The P-loop guanosine triphosphatases (GTPases) control a multitude of biological processes, ranging from cell division, cell cycling, and signal transduction, to ribosome assembly and protein synthesis. GTPases exert their control by interchanging between an inactive GDP-bound state and an active GTP-bound state, thereby acting as molecular switches. The common denominator of GTPases is the highly conserved guanine nucleotide-binding (G) domain that is responsible for binding and hydrolysis of guanine nucleotides .

Within the translation factor-related (TRAFAC) class of P-loop GTPases, the HflX-type is a widely distributed family of GTPases that interact with the large ribosomal subunit. The broad phylogenetic distribution pattern of HflX GTPases in Bacteria, Archaea, and Eukaryotes (including human) suggests a basic cellular function for this protein family.

The HflX-type G domain is composed of six β-strands and five α-helices . It consists of the following conserved sequence motifs: the G1 motif (or P-loop), consensus GX4GK(S/T), which is responsible for interacting with the alpha and beta-phosphates of nucleotide di- and triphosphates; the G2 variable effector loop (DXnT); the G3 motif (DX2G), which interacts with the gamma-phosphate of nucleotide triphosphates; and the G4 motif (NKXD), which conveys specificity for guanine nucleotides through hydrogen bonding to the base .
Glycerophosphodiester phosphodiesterase domain (GP_PDE_dom)
Type: Domain

This entry represents the GP-PDE domain.

The glycerophosphodiester phosphodiesterases (GD-PDEs) were initially characterised in bacteria, where they have functional roles for production of metabolic carbon and phosphate sources from glycerophosphodiesters and in adherence to and degradation of mammalian host-cell membranes. Mammalian GP- GDEs have been identified more recently and shown to be implicated in several physiological functions. GD-PDEs are involved in glycerol metabolism and catalyze the reaction of glycerophosphodiester and water to alcohol and sn-glycerol-3-phosphate. They display broad specificity for glycerophosphodiesters, such as glycerophosphocholine, glycerophosphoethanolamine, glycerophosphoglycerol and bis(glycerophosphoglycerol).

The GP-PDE domain adopts the ubiquitous triosephosphate isomerase (TIM) barrel α/β fold. The TIM barrel is comprised of an eight-stranded parallel β-sheet barrel surrounded by eight α-helices. There is a small insertion to the conventional TIM barrel structure referred to as the GDPD-insertion (GDPD-I). The GDPD-I is comprised of β strands, α-helices (H3 and H4), and 3/10 helices. Although the TIM barrel and a small insertion are unique for GP-PDE family, there are subtle differences in size and topology of each domain .

Some proteins known to contain a GP-PDE domain are listed below:

Bacterial glycerophosphoryl diester phosphodiesterase GlpQ (EC 3.1.4.46).

Bacterial gylcerophosphoryl diester phosphodiesterase UgpQ (EC 3.1.4.46).

Mammalian glycerophosphodiester phosphodiesterase 1 (GDE1) (EC 3.1.4.44) (or MMIR16) , an integral membrane glycoprotein that interacts with regulator of G protein signaling proteins. It hydrolyzes glycerophosphoinositols (GPIs) producing inositol and glycerol 3-phosphate.

Mammalian glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5) (EC 3.1.-.-) (or GDE2) .

Mammalian glycerophosphoinositol inositolphosphodiesterase GDPD2 (or GDE3) (EC 3.1.4.43) , up-regulated during osteoblast differentiation and can affect cell morpholgy. It hydrolyzes glycerophosphoinositol (GroPIns), producing inositol 1-phosphate and glycerol.

Mammalian glycerophosphodiester phosphodiesterase domain-containing protein 1 (GDPD1) (EC 3.1.-.-) (or GDE4) .

Mammalian glycerophosphocholine phosphodiesterase GPCPD1 (EC 3.1.4.2) (or GDE5), selectively hydrolyzes glycerophosphocholine (GroPCho) and controls skeletal muscle development .

Mammalian glycerophosphodiester phosphodiesterase domain-containing protein 4 (GDPD4) (EC 3.1.-.-) (or GDE6) .
Peptidase family S6 domain (Peptidase_S6_dom)
Type: Domain

Autotransporters (ATs) represent a large superfamily of virulence factors produced by Gram-negative bacteria. ATs have evolved a unique export mechanism. Initially the protein is synthetised with an N-terminal leader peptide directing the protein to the periplasm via the signal recognition particle. Once across the inner membrane, the C-terminal domain form a β-barrel structure allowing the passenger domain to escape to the external medium, where it is released proteolytically from the cell. The 300-residue peptidase family S6 domain is found in a subfamily of autotransporters including:

Neisseria gonorrhoeae IgA-specific serine endopeptidase autotransporter.

Haemophilus influenzae immunoglobulin A1 protease autotransporter.

Enteropathogenic Escherichia coli serine protease EspC.

Enterohemorrhagic Escherichia coli serine protease EspP.

Enteroaggregative Escherichia coli plasmid-encoded toxin (Pet).

Uropathogenic Escherichia coli serine protease Sat autotransporter.

Pathogenic Escherichia coli hemoglobin-binding protease Hbp autotransporter.

Avian pathogenic Escherichia coli temperature-sensitive hemagglutinin Tsh autotransporter.

Avian pathogenic Escherichia coli Vat.

Shigella flexneri serine protease Pic autotransporter.

Shigella flexneri serine protease SepA autotransporter.

The peptidase family S6 domain mediates intermolecular autoproteolysis, resulting in release of the passenger domain from the bacterial surface. It has a globular shape including six β strands rolled into a barrel-like structure with several long β hairpins over its surface. The catalytic triad is composed of Ser, Asp, and His .

The peptidase family S6 is a member of the SA (chymotrypsin) clan .