SII-SWORD/CoKE huggingface dataset:
Plasmid recombination enzyme (Mob_Pre)
Type: Family

With some plasmids, recombination can occur in a site specific manner that is independent of RecA. In such cases, the recombination event requires another protein called Pre. Pre is a plasmid recombination enzyme. This protein is also known as Mob (conjugative mobilisation) .
Arginine repressor (Arg_repress)
Type: Family

The arginine dihydrolase (AD) pathway is found in many prokaryotes and some primitive eukaryotes, an example of the latter being Giardia lamblia (Giardia intestinalis) . The three-enzyme anaerobic pathway breaks down L-arginine to form 1 mol of ATP, carbon dioxide and ammonia. In simpler bacteria, the first enzyme, arginine deiminase, can account for up to 10% of total cell protein .

Most prokaryotic arginine deiminase pathways are under the control of a repressor gene, termed ArgR . This is a negative regulator, and will only release the arginine deiminase operon for expression in the presence of arginine . The crystal structure of apo-ArgR from Bacillus stearothermophilus has been determined to 2.5A by means of X-ray crystallography . The protein exists as a hexamer of identical subunits, and is shown to have six DNA-binding domains, clustered around a central oligomeric core when bound to arginine. It predominantly interacts with A.T residues in ARG boxes. This hexameric protein binds DNA at its N terminus to repress arginine biosyntheis or activate arginine catabolism. Some species have several ArgR paralogs. In a neighbour-joining tree, some of these paralogous sequences show long branches and differ significantly from the well-conserved C-terminal region.
Alcohol dehydrogenase, iron-type/glycerol dehydrogenase GldA (ADH_Fe/GldA)
Type: Domain

Alcohol dehydrogenase (

) (ADH) catalyses the reversible oxidation of ethanol to acetaldehyde with the concomitant reduction of NAD. Currently three, structurally and catalytically, different types of alcohol dehydrogenases are known:

Zinc-containing 'long-chain' alcohol dehydrogenases.

Insect-type, or 'short-chain' alcohol dehydrogenases.

Iron-containing alcohol dehydrogenases.

Iron-containing ADH's have been found in yeast (gene ADH4) , as well as in Zymomonas mobilis (gene adhB) . These two iron-containing ADH's are closely related to the following enzymes:

Escherichia coli lactaldehyde reductase (also known as propanediol oxidoreductase) (

) (gene fucO) , an enzyme involved in the metabolism of fucose and which also seems to contain ferrous ion(s).

Clostridium acetobutylicum NADPH- and NADH-dependent butanol dehydrogenases (

) (genes adh1, bdhA and bdhB) , an enzyme which has activity using butanol and ethanol as substrates.

E. coli aldehyde-alcohol dehydrogenase (AdhE) , an iron-dependent enzyme which harbor three different activities: alcohol dehydrogenase, acetaldehyde dehydrogenase (acetylating) (

) and pyruvate-formate-lyase deactivase.

Bacterial glycerol dehydrogenase (

) (gene gldA or dhaD) .

Clostridium kluyveri NAD-dependent 4-hydroxybutyrate dehydrogenase (4hbd) (

).

Citrobacter freundii and Klebsiella pneumoniae 1,3-propanediol dehydrogenase (

) (gene dhaT).

Bacillus methanolicus NAD-dependent methanol dehydrogenase (

) .

E. coli and Salmonella typhimurium ethanolamine utilization protein eutG.

E. coli hypothetical protein yiaY.
Melanocortin/ACTH receptor (Melcrt_ACTH_rcpt)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups . The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices .

Adrenocorticotrophin (ACTH), melanocyte-stimulating hormones (MSH) and beta-endorphin are peptide products of pituitary pro-opiomelanocortin. ACTH regulates synthesis and release of glucocorticoids and aldosterone in the adrenal cortex; it also has a trophic action on these cells. ACTH and beta-endorphin are synthesised and released in response to corticotrophin-releasing factor at times of stress (heat, cold, infections, etc.) -their release leads to increased metabolism and analgesia. MSH has a trophic action on melanocytes, and regulates pigment production in fish and amphibia. The ACTH receptor is found in high levels in the adrenal cortex -binding sites are present in lower levels in the CNS. The MSH receptor is expressed in high levels in melanocytes, melanomas and their derived cell lines. Receptors are found in low levels in the CNS. MSH regulates temperature control in the septal region of the brain and releases prolactin from the pituitary.
Phosphoglucose isomerase (PGI) (G6P_Isomerase)
Type: Family

Phosphoglucose isomerase (

) (PGI) is a dimeric enzyme that catalyses the reversible isomerization of glucose-6-phosphate and fructose-6-phosphate. PGI is involved in different pathways: in most higher organisms it is involved in glycolysis; in mammals it is involved in gluconeogenesis; in plants in carbohydrate biosynthesis; in some bacteria it provides a gateway for fructose into the Entner-Doudouroff pathway. The multifunctional protein, PGI, is also known as neuroleukin (a neurotrophic factor that mediates the differentiation of neurons), autocrine motility factor (a tumour-secreted cytokine that regulates cell motility), differentiation and maturation mediator and myofibril-bound serine proteinase inhibitor, and has different roles inside and outside the cell. In the cytoplasm, it catalyses the second step in glycolysis, while outside the cell it serves as a nerve growth factor and cytokine .
Dictyostelium (slime mold) repeat (S_mold_repeat)
Type: Repeat

Several Dictyostelium species have proteins that contain conserved repeats. These proteins have been variously described as 'extracellular matrix protein B', 'cyclic nucleotide phosphodiesterase inhibitor precursor', 'prestalk protein precursor', 'putative calmodulin-binding protein CamBP64', and 'cysteine-rich, acidic integral membrane protein precursor' as well as 'hypothetical protein'.
GMP synthase, C-terminal (GMP_synth_C)
Type: Domain

This entry represents the C-terminal domain of bacterial GMP synthase [glutamine-hydrolyzing] sequences and similar proteins found in all cellular organisms.

The amidotransferase family of enzymes utilises the ammonia derived from the hydrolysis of glutamine for a subsequent chemical reaction catalyzed by the same enzyme. The ammonia intermediate does not dissociate into solution during the chemical transformations . GMP synthetase is a glutamine amidotransferase from the
de novo
purine biosynthetic pathway. The C-terminal domain is specific to the GMP synthases

. In prokaryotes this domain mediates dimerisation. Eukaryotic GMP synthases are monomers. This domain in eukaryotes includes several large insertions that may form globular domains .
Glycosyl transferase family 29 (Glyco_trans_29)
Type: Family

Glycosyltransferase family 29 (

) comprises enzymes with a number of known activities; sialyltransferase (

), beta-galactosamide alpha-2,6-sialyltransferase (

), alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase (

), beta-galactoside alpha-2,3-sialyltransferase (

), N-acetyllactosaminide alpha-2,3-sialyltransferase (

), alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase (

); lactosylceramide alpha-2,3-sialyltransferase (

). These enzymes use a nucleotide monophosphosugar as the donor (CMP-NeuA) instead of a nucleotide diphosphosugar.

The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases. These enzymes catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. A classification of glycosyltransferases using nucleotide diphospho-sugar, nucleotide monophospho-sugar and sugar phosphates ([ec:2.4.1.-]) and related proteins into distinct sequence based families has been described . This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. The same three-dimensional fold is expected to occur within each of the families. Because 3-D structures are better conserved than sequences, several of the families defined on the basis of sequence similarities may have similar 3-D structures and therefore form 'clans'.
Picornavirus capsid (Picornavirus_capsid)
Type: Domain

This domain occurs in the capsid proteins of picornaviruses, which are non-enveloped plus-strand ssRNA animal viruses with icosahedral capsids. They include rhinovirus (common cold) and poliovirus.

The atomic structure of echovirus 1 (a member of the enterovirus genus of the picornavirus family) has been determined using cryo-crystallography and refined to 3.55 A resolution . The common structure is an 8-stranded β sandwich which can have one or two extra strands.
Transferrin-binding protein B, C-lobe/N-lobe beta-barrel domain (TbpB_B_D)
Type: Domain

This domain is found in the N- and C-terminal lobe of Transferrin-binding protein B. It is also found in Neisserial heparin-binding protein (NHBA) that is responsible for capturing host heparin, a natural glycosaminoglycan. These domains have been structurally characterised

,

.

Bacterial lipoproteins represent a large group of specialised membrane proteins that perform a variety of functions including maintenance and stabilization of the cell envelope, protein targeting and transit to the outer membrane, membrane biogenesis, and cell adherence . Pathogenic Gram-negative bacteria within the Neisseriaceae and Pasteurellaceae families rely on a specialised uptake system, characterised by an essential surface receptor complex that acquires iron from host transferrin (Tf) and transports the iron across the outer membrane. They have an iron uptake system composed of surface exposed lipoprotein, Tf-binding protein B (TbpB), and an integral outer-membrane protein, Tf-binding protein A (TbpA), that together function to extract iron from the host iron binding glycoprotein (Tf).

TbpB is a bilobed (N and C lobe) lipid-anchored protein with each lobe consisting of an eight-stranded β-barrel flanked by a 'handle' domain made up of four (N lobe) or eight (C lobe) β-strands . TbpB extends from the outer membrane surface by virtue of an N-terminal peptide region that is anchored to the outer membrane by fatty acyl chains on the N-terminal cysteine and is involved in the initial capture of iron-loaded Tf . This domain family is found in C and N lobe eight stranded β-barrel region of TbpB proteins. The eight-stranded barrel domains in N and C lobe draw comparisons to eight-stranded β-barrel outer-membrane protein W (OmpW). However, the barrel domains of TbpB have the hydrophobic residues line the inner surface of the β-barrels to create a stable hydrophobic core .
SAM-dependent methyltransferase RsmB-F/NOP2-type domain (MeTrfase_RsmB-F_NOP2_dom)
Type: Domain

This domain is found in a group of class I-like SAM-binding methyltransferases from all cellular organisms. It includes the catalytic core of this enzimes (

).

The catalytic domain of ribosomal RNA cysteine methyltransferases is highly conserved in archaeal, bacterial and eukaryotic proteins . It is located at the C-terminal end in ribosomal RNA methyltransferase B (RsmB, Sun, Fmu) and Nop2 and towards the N-terminal in RsmF. Escherichia coli RsmB methylates cytosine C967 in 16S rRNA . RsmF is a multi-site-specific methyltransferase . Nop2 methylates cytosine C2870 in the 25S rRNA of S. cerevisiae and is critical for 60S biogenesis .
NAD-dependent DNA ligase (DNA_ligase)
Type: Family

DNA ligase (polydeoxyribonucleotide synthase) is the enzyme that joins two DNA fragments by catalyzing the formation of an internucleotide ester bond between phosphate and deoxyribose. It is active during DNA replication, DNA repair and DNA recombination. There are two forms of DNA ligase: one requires ATP (

), the other NAD (

).

This family is predominantly composed of NAD-dependent bacterial DNA ligases. They are proteins of about 75 to 85 kDa whose sequence is well conserved . They also show similarity to yicF, an Escherichia coli hypothetical protein of 63 kDa.
WD40 repeat (WD40_rpt)
Type: Repeat

WD-40 repeats (also known as WD or beta-transducin repeats) are short ~40 amino acid motifs, often terminating in a Trp-Asp (W-D) dipeptide. WD40 repeats usually assume a 7-8 bladed β-propeller fold, but proteins have been found with 4 to 16 repeated units, which also form a circularised β-propeller structure. WD-repeat proteins are a large family found in all eukaryotes and are implicated in a variety of functions ranging from signal transduction and transcription regulation to cell cycle control and apoptosis. Repeated WD40 motifs act as a site for protein-protein or protein-DNA interaction, and proteins containing WD40 repeats are known to serve as platforms for the assembly of protein complexes or mediators of transient interplay among other proteins . The specificity of the proteins is determined by the sequences outside the repeats themselves. Examples of such complexes are G proteins (beta subunit is a β-propeller), TAFII transcription factor, and E3 ubiquitin ligase . In Arabidopsis spp., several WD40-containing proteins act as key regulators of plant-specific developmental events.
Neurokinin receptor (Neurokn_rcpt)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups . The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices .

Neuropeptide receptors are present in very small quantities in the cell and are embedded tightly in the plasma membrane. The neuropeptides exhibit a high degree of functional diversity through both regulation of peptide production and through peptide-receptor interaction . The mammalian tachykinin system consists of 3 distinct peptides: substance P, substance K and neuromedin K. All possess a common spectrum of biological activities, including sensory transmission in the nervous system and contraction/ relaxation of peripheral smooth muscles, and each interacts with a specific receptor type.
Phox homology (PX_dom)
Type: Domain

The PX (phox) domain occurs in a variety of eukaryotic proteins and have been implicated in highly diverse functions such as cell signalling, vesicular trafficking, protein sorting and lipid modification . PX domains are important phosphoinositide-binding modules that have varying lipid-binding specificities . The PX domain is approximately 120 residues long , and folds into a three-stranded β-sheet followed by three -helices and a proline-rich region that immediately preceeds a membrane-interaction loop and spans approximately eight hydrophobic and polar residues. The PX domain of neutrophil cytosol factor 1 (p47phox) binds to the SH3 domain in the same protein . Phosphorylation of p47(phox), a cytoplasmic activator of the microbicidal phagocyte oxidase (phox), elicits interaction of p47(phox) with phoinositides. The protein phosphorylation-driven conformational change of p47(phox) enables its PX domain to bind to phosphoinositides, the interaction of which plays a crucial role in recruitment of p47(phox) from the cytoplasm to membranes and subsequent activation of the phagocyte oxidase. The lipid-binding activity of this protein is normally suppressed by intramolecular interaction of the PX domain with the C-terminal Src homology 3 (SH3) domain .

The PX domain is conserved from yeast to human. A multiple alignment of representative PX domain sequences from eukaryotic proteins , shows relatively little sequence conservation, although their structure appears to be highly conserved. Although phosphatidylinositol-3-phosphate (PtdIns(3)P) is the primary target of PX domains, binding to phosphatidic acid, phosphatidylinositol-3,4-bisphosphate (PtdIns(3,4)P2), phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P2), phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2), and phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) has been reported as well. The PX-domain is also a protein-protein interaction domain .
Large ribosomal subunit protein bL27 (Ribosomal_bL27)
Type: Family

Large ribosomal subunit protein bL27 (known as L27) is a protein from the large (50S) subunit; it is essential for ribosome function, but its exact role is unclear. It belongs to a family of ribosomal proteins, examples of which are found in bacteria, chloroplasts of plants and red algae and the mitochondria of fungi (e.g. MRP7 from yeast mitochondria). The schematic relationship between these groups of proteins is shown below.

Bacterial L27 Nxxxxxxxxx
Algal L27 Nxxxxxxxxx
Plant L27 tttttNxxxxxxxxxxxxx
Yeast MRP7 tttNxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx

't': transit peptide.
'N': N-terminal of mature protein.

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Flagellar motor switch protein FliM (Flag_FliM)
Type: Family

The flagellar motor switch in Escherichia coli and Salmonella typhimurium regulates the direction of flagellar rotation and hence controls swimming behaviour . The switch is a complex apparatus that responds to signals transduced by the chemotaxis sensory signalling system during chemotactic behaviour . CheY, the chemotaxis response regulator, is believed to act directly on the switch to induce tumbles in the swimming pattern, but no physical interactions of CheY and switch proteins have yet been demonstrated.

The switch complex comprises at least three proteins - FliG, FliM and FliN. It has been shown that FliG interacts with FliM, FliM interacts with itself, and FliM interacts with FliN . Several residues within the middle third of FliG appear to be strongly involved in the FliG-FliM interaction, with residues near the N or C termini being less important . Such clustering suggests that FliG-FliM interaction plays a central role in switching.

Analysis of the FliG, FliM and FliN sequences shows that none are especially hydrophobic or appear to be integral membrane proteins . This result is consistent with other evidence suggesting that the proteins may be peripheral to the membrane, possibly mounted on the basal body M ring .