SII-SWORD/CoKE huggingface dataset:
Solute-binding protein family 3, conserved site (SBP_3_CS)
Type: Conserved_site

Bacterial high affinity transport systems are involved in active transport of solutes across the cytoplasmic membrane. Most of the bacterial ABC (ATP-binding cassette) importers are composed of one or two transmembrane permease proteins, one or two nucleotide-binding proteins and a highly specific periplasmic solute-binding protein. In Gram-negative bacteria the solute-binding proteins are dissolved in the periplasm, while in archaea and Gram-positive bacteria, their solute-binding proteins are membrane-anchored lipoproteins .

On the basis of sequence similarities, the vast majority of these solute-binding proteins can be grouped into eight families or clusters, which generally correlate with the nature of the solute bound. This entry represents a conserved site found in the extracellular solute-binding protein family 3 members from Gram-positive bacteria, Gram-negative bacteria and archaea.

Familiy 3 members include:

Histidine-binding protein (gene hisJ) of Escherichia coli and related bacteria. An homologous lipoprotein exists in Neisseria gonorrhoeae.

Lysine/arginine/ornithine-binding proteins (LAO) (gene argT) of Escherichia coli and related bacteria are involved in the same transport system than hisJ. Both solute-binding proteins interact with a common membrane-bound receptor hisP of the binding protein dependent transport system HisQMP.

Glutamine-binding proteins (gene glnH) of Escherichia coli and Bacillus stearothermophilus.

Glutamate-binding protein (gene gluB) of Corynebacterium glutamicum.

Arginine-binding proteins artI and artJ of Escherichia coli.

Nopaline-binding protein (gene nocT) from Agrobacterium tumefaciens.

Octopine-binding protein (gene occT) from Agrobacterium tumefaciens.

Major cell-binding factor (CBF1) (gene: peb1A) from Campylobacter jejuni.

Bacteroides nodosus protein aabA.

Cyclohexadienyl/arogenate dehydratase of Pseudomonas aeruginosa, a periplasmic enzyme which forms an alternative pathway for phenylalanine biosynthesis.

Escherichia coli protein fliY.

Vibrio harveyi protein patH.

Escherichia coli hypothetical protein ydhW.

Bacillus subtilis hypothetical protein yckB.

Bacillus subtilis hypothetical protein yckK.
RsmB/NOL1/NOP2-like, conserved site (RsmB/NOL1/NOP2-like_CS)
Type: Conserved_site

This entry represents a highly conserved region found in the conserved central domain of a group of class I-like SAM-binding methyltransferases found in archaea, bacterial and eukaryotes, including Trm4 from Methanocaldococcus jannaschii, RsmB from Escherichia coli (also known as Sun), NOP2 from fission yeast and human NOL1.
Tubulin/FtsZ, 2-layer sandwich domain (Tubulin/FtsZ_2-layer-sand-dom)
Type: Domain

This domain is found in the tubulin alpha, beta and gamma chains, as well as the bacterial FtsZ family of proteins. These proteins are GTPases and are involved in polymer formation. Tubulin is the major component of microtubules, while FtsZ is the polymer-forming protein of bacterial cell division, it is part of a ring in the middle of the dividing cell that is required for constriction of cell membrane and cell envelope to yield two daughter cells. FtsZ can polymerise into tubes, sheets, and rings
in vitro
and is ubiquitous in bacteria and archaea. This is the C-terminal domain.
Queuosine biosynthesis protein QueC (QueC)
Type: Family

This family represents Queuosine biosynthesis protein (QueC), also known as 7-cyano-7-deazaguanine synthas, which catalyses the ATP-dependent conversion of 7-carboxy-7-deazaguanine (CDG) to 7-cyano-7-deazaguanine (preQ0) .
L-seryl-tRNA selenium transferase-like (SelA-like)
Type: Family

In prokaryotes, the incorporation of selenocysteine as the 21st amino acid, encoded by TGA, requires several elements: SelC is the tRNA itself, SelD acts as a donor of reduced selenium, SelA modifies a serine residue on SelC into selenocysteine, and SelB is a selenocysteine-specific translation elongation factor. 3-prime or 5-prime non-coding elements of mRNA have been found as probable structures for directing selenocysteine incorporation.

This family describes SelA and pyridoxal phosphate enzymes of unknown function. A close homologue of SelA is found in Helicobacter pylori, but all other required elements are missing and the protein is shorter at the N terminus than SelA from other species.
DNA polymerase 1 (DNA_polymerase_1)
Type: Family

DNA carries the biological information that instructs cells how to exist in an ordered fashion. Accurate replication is thus one of the most important events in the cell life cycle. This function is mediated by DNA-directed DNA polymerases, which add nucleotide triphosphate (dNTP) residues to the 3'-end of the growing DNA chain, using a complementary DNA as template. Small RNA molecules are generally used as primers for chain elongation, although terminal proteins may also be used. DNA-dependent DNA polymerases have been grouped into families, denoted A, B and X, on the basis of sequence similarities . Members of family A, which includes bacterial and bacteriophage polymerases, share significant similarity to Escherichia coli polymerase I; hence family A is also known as the pol I family. The bacterial polymerases also contain an exonuclease activity, which is coded for in the N-terminal portion. Three motifs, A, B and C , are seen to be conserved across all DNA polymerases, with motifs A and C also seen in RNA polymerases. They are centred on invariant residues, and their structural significance was implied from the Klenow (E. coli) structure. Motif A contains a strictly-conserved aspartate at the junction of a β-strand and an α-helix; motif B contains an α-helix with positive charges; and motif C has a doublet of negative charges, located in a β-turn-beta secondary structure .
Glucosamine-6-phosphate isomerase, conserved site (Glucosamine6P_isomerase_CS)
Type: Conserved_site

Glucosamine-6-phosphate isomerase (

) catalyses the conversion of D-glucosamine 6-phosphate (GlcN6P) to D-fructose 6-phosphate and ammonia. This is the last step in the pathway for N-acetylglucosamine (GlcNAC) utilization in bacteria such as Escherichia coli (gene nagB) or in fungi such as Candida albicans (Yeast) (gene NAG1). The structure of this enzyme from E. coli (NagB) is described as a modified NAD-binding domain, and undergoes allosteric conformational changes that regulate its function . The reaction steps involve opening of the pyranose ring of the substrate and a sequence of general base-catalysed reactions to bring about isomerisation and deamination .

This entry represents a conserved region located in the central part of these enzymes. This region contains a conserved histidine which has been shown , in NagB, to be important for the pyranose ring-opening step of the catalytic mechanism.
Outer membrane lipoprotein carrier protein LolA, Proteobacteria (OM_lipoprot_carrier_LolA_Pbac)
Type: Family

In Escherichia coli, lipoproteins are anchored to the periplasmic side of either the inner or outer membrane through N-terminal lipids, depending on the lipoprotein-sorting signal present at position 2 . Five Lol proteins are involved in the sorting and outer membrane localization of lipoproteins. LolCDE, an ATP binding cassette (ABC) transporter, in the inner membrane releases outer membrane-directed lipoproteins from the inner membrane in an ATP-dependent manner, leading to the formation of a water-soluble complex between the lipoprotein and the molecular chaperone, LolA. The LolA-lipoprotein complex crosses the periplasm and then interacts with outer membrane receptor LolB, which is essential for the anchoring of lipoproteins to the outer membrane .

E. coli lipoproteins are anchored to the inner or outer membrane depending on the residue at position 2. Aspartate at this position makes lipoproteins specific to the inner membrane, whereas other residues cause the release of lipoproteins from the inner membrane .
Checkpoint protein Rad17/Rad24, fungi/metazoa (Rad17/Rad24_fun/met)
Type: Family

This entry consists of the checkpoint protein Rad24 from budding yeast and its homologue, Rad17, from other organisms. This entry does not include Rad17 from plants.

In Saccharomyces cerevisiae, Rad24 forms a complex with replication factor C (RFC) proteins, including Rfc2, Rfc3, Rfc4, and Rfc5. When DNA damage is detected, the Rad24-RFC complex loads Rad17-Mec3-Ddc1 complex onto chromatin and activates DNA damage checkpoint, which then leads to cell cycle arrest and DNA repair . The Rad24-RFC complex is involved in both the mitotic and meiotic checkpoints . Besides checkpoint activation, Rad24 is also involved in double-strand break ends processing, DNA repair and telomere maintenance .
Rad4/PNGase transglutaminase-like fold (Rad4/PNGase_transGLS-fold)
Type: Domain

RAD4/Xp-C proteins contain an ancient transglutaminase fold that is also found in peptide-N-glycanases (PNGases), which remove glycans from glycoproteins during their degradation. The PNGases retain the catalytic triad that is typical of this fold and are predicted to have a reaction mechanism similar to that involved in transglutamination. In contrast, the RAD4/Xp-C proteins are predicted to be inactive and are likely to only possess the interaction function in DNA repair .
Rad4 beta-hairpin domain 1 (Rad4_beta-hairpin_dom1)
Type: Domain

This short domain is found in the Rad4 protein. This domain binds to DNA .
Rad4 beta-hairpin domain 2 (BHD_2)
Type: Domain

This short domain is found in the Rad4 protein. This domain binds to DNA .
Rad4 beta-hairpin domain 3 (Rad4_beta-hairpin_dom3)
Type: Domain

This short domain is found in the Rad4 protein. This domain binds to DNA .
RecT family (RecT_fam)
Type: Family

The DNA single-strand annealing proteins (SSAPs), such as RecT, Red-beta, ERF and Rad52, function in RecA-dependent and RecA-independent DNA recombination pathways . This family includes RecT and related proteins.
Antenna complex, alpha subunit (Antenna_alpha)
Type: Family

The antenna complexes of photosynthetic bacteria function as light-harvesting systems that absorb light and transfer the excitation energy to the reaction centres. The antenna complexes usually comprise 2 polypeptides (alpha- and beta-chains), 2-3 bacteriochlorophyll molecules and some carotenoids .
The alpha- and beta-chains are small proteins of 40-70 residues. Each has an N-terminal hydrophilic cytoplasmic domain, a single transmembrane (TM) region, and a small C-terminal hydrophilic periplasmic domain. In both chains, the TM domain houses a conserved His residue, presumed to be involved in binding the magnesium atom of a bacteriochlorophyll group. The beta-chains are characterised by a further histidine at the C-terminal extremity of the cytoplasmic domain, which is also thought to be involved in bacteriochlorophyll binding.

This family represents the antenna pigment protein (also known as light harvesting protein B) alpha chain.
Squalene cyclase (Squalene_cyclase)
Type: Family

Several enzymes catalyse mechanistically related reactions which involve the highly complex cyclic rearrangement of squalene or its 2,3 oxide. Squalene cyclase (SQCY) and 2,3-oxidosqualene cyclase (OSQCY) are integral membrane proteins that catalyse a cationic cyclisation cascade converting linear triterpenes to fused ring compounds . Lanosterol synthase (

) (oxidosqualene-lanosterol cyclase) catalyses the cyclisation of (S)-2,3-epoxysqualene to lanosterol, the initial precursor of cholesterol, steroid hormones and vitamin D in vertebrates and of ergosterol in fungi (gene ERG7). Cycloartenol synthase (

) (2,3-epoxysqualene-cycloartenol cyclase), is a plant enzyme that catalyses the cyclization of (S)-2,3-epoxysqualene to cycloartenol , and hopene synthase (

) (squalene-hopene cyclase), is a bacterial enzyme that catalyses the cyclisation of squalene into hopene or diplopterol, a key step in hopanoid (triterpenoid) metabolism also found in Aspergillus fumigatus as part of the gene cluster that mediates the biosynthesis fumihopaside A . These enzymes are evolutionary related proteins of about 70 to 85kDa and have an alpha 6 - alpha 6 barrel fold. Deletion of a single glycine residue of Alicyclobacillus acidocaldarius SQCY alters its substrate specificity into that of eukaryotic OSQCY . Both enzymes have a second minor domain, which forms an α-α barrel that is inserted into the major domain.
ArsR-type transcription regulator, HTH motif (ArsR_HTH)
Type: Conserved_site

Bacterial transcription regulatory proteins that bind DNA via a helix-turn-helix (HTH) motif can be grouped into families on the basis of sequence similarities. One such group, termed arsR, includes several proteins that appear to dissociate from DNA in the presence of metal ions: arsR, which functions as a transcriptional repressor of an arsenic resistance operon; smtB from Synechococcus sp. (strain PCC 7942), which acts as a transcriptional repressor of the smtA gene that codes for a metallothionein; cadC, a transcription regulator of the cadmium resistance (cad) operon which encodes a Cd/Pb-specific efflux ATPase .

The HTH motif is thought to be located in the central part of these proteins . The motif is characterised by a number of well-conserved residues: at its N-terminal extremity is a cysteine residue; a second Cys is found in arsR and cadC, but not in smtA; and at the C terminus lie one or two histidines. These residues may be involved in metal-binding (Zn in smtB; metal-oxyanions such as arsenite, antimonite and arsenate for arsR; and cadmium for cadC) . It is believed that binding of a metal ion could induce a conformational change that would prevent the protein from binding DNA .
Transcription regulator HTH, Crp-type, conserved site (Tscrpt_reg_HTH_Crp-type_CS)
Type: Conserved_site

The crp-type HTH domain is a DNA-binding, winged helix-turn-helix (wHTH) domain of about 70-75 amino acids present in transcription regulators of the crp-fnr family, involved in the control of virulence factors, enzymes of aromatic ring degradation, nitrogen fixation, photosynthesis, and various types of respiration. The crp-fnr family is named after the first members identified in Escherichia coli: the well characterised cyclic AMP receptor protein CRP or CAP (catabolite activator protein) and the fumarate and nitrate reductase regulator Fnr. crp-type HTH domain proteins occur in most bacteria and in chloroplasts of red algae. The DNA-binding HTH domain is located in the C-terminal part; the N-terminal part of the proteins of the crp-fnr family contains a nucleotide-binding domain and a dimerisation/linker helix occurs in between. The crp-fnr regulators predominantly act as transcription activators, but can also be important repressors, and respond to diverse intracellular and exogenous signals, such as cAMP, anoxia, redox state, oxidative and nitrosative stress, carbon monoxide, nitric oxide or temperature .
Ribonuclease PH, conserved site (RNase_PH_CS)
Type: Conserved_site

Prokaryotic ribonuclease PH (

) (RNase PH) is a phosphorolytic exoribonuclease that removes nucleotide residues following the -CCA terminus of tRNA and adds nucleotides to the ends of RNA molecules by using nucleoside diphosphates as substrates . There is a similar protein in Caenorhabditis elegans that belongs to this group.
Cell wall/choline-binding repeat (Cell_wall/Cho-bd_repeat)
Type: Repeat

The cell wall-binding repeat (CW) is an about 20 amino acid residue module, essentially found in two bacterial Gram-positive protein families; the choline binding proteins and glucosyltransferases (

). In choline-binding proteins cell wall binding repeats bind to choline moieties of both teichoic and lipoteichoic acids, two components peculiar to the cell surface of Gram-positive bacteria . In glucosyltransferases the region spanning the CW repeats is a glucan binding domain .

Several crystal structures of CW have been solved . In the choline binding protein LytA, the repeats adopt a solenoid fold consisting exclusively of β-hairpins that stack to form a left-handed superhelix with a boomerang-like shape. The choline groups bind between β-hairpin 'steps' of the superhelix . In Cpl-1 CW repeats assemble in two sub-domains: an N-terminal superhelical moiety similar to the LytA one and a C-terminal β-sheet involved in interactions with the lysozyme domain. Choline is bound between repeats 1 and 2, and, 2 and 3 of the superhelical sub-domain .

Some proteins known to contain cell-wall binding repeats include:

Pneumococcal N-acetylmuramoyl-L-alanine amidase (autolysin, lytA) (

). It is a surface-exposed enzyme that rules the self-destruction of pneumococcal cells through degradation of their peptidoglycan backbone. It mediates the release of toxic substances that damage the host tissues.

Pneumococcal endo-beta-N-acetylglucosaminidase (lytB) (

). It plays an important role in cell wall degradation and cell separation.

Pneumococcal teichoic acid phosphorylcholine esterase (pce or cbpE), a cell wall hydrolase important for cellular adhesion and colonisation.

Lactobacillales glucosyltransferase. It catalyses the transfer of glucosyl units from the cleavage of sucrose to a growing chain of glucan.

Clostridium difficile toxin A (tcdA) and toxin B (tcdb). They are the causative agents of the antibiotic-associated pseudomembranous colitis. They are intracellular acting toxins that reach their targets after receptor-mediated endocytosis.

Clostridium acetobutylicum cspA protein.

Siphoviridae bacteriophages N-acetylmuramoyl-L-alanine amidase. It lyses the bacterial host cell wall.

Podoviridae lysozyme protein (cpl-1). It is capable of digesting the pneumococcal cell wall.

The cell wall binding repeats are also known as the choline-binding repeats (ChBr) or the choline-binding domain (ChBD).
Carbonic anhydrase, alpha-class, conserved site (Carbonic_anhydrase_a-class_CS)
Type: Conserved_site

Carbonic anhydrases (CA:

) are zinc metalloenzymes which catalyse the reversible hydration of carbon dioxide to bicarbonate . CAs have essential roles in facilitating the transport of carbon dioxide and protons in the intracellular space, across biological membranes and in the layers of the extracellular space; they are also involved in many other processes, from respiration and photosynthesis in eukaryotes to cyanate degradation in prokaryotes. There are five known evolutionarily distinct CA families (alpha, beta, gamma, delta and epsilon) that have no significant sequence identity and have structurally distinct overall folds. Some CAs are membrane-bound, while others act in the cytosol; there are several related proteins that lack enzymatic activity. The active site of alpha-CAs is well described, consisting of a zinc ion coordinated through 3 histidine residues and a water molecule/hydroxide ion that acts as a potent nucleophile. The enzyme employs a two-step mechanism: in the first step, there is a nucleophilic attack of a zinc-bound hydroxide ion on carbon dioxide; in the second step, the active site is regenerated by the ionisation of the zinc-bound water molecule and the removal of a proton from the active site . Beta-and gamma-CAs also employ a zinc hydroxide mechanism, although at least some beta-class enzymes do not have water directly coordinated to the metal ion.

This entry represents a conserved site based around one of the zinc-binding histidines in the alpha class of carbonic anhydrases.
Peptidase M24A, methionine aminopeptidase, subfamily 2, binding site (Pept_M24A_MAP2_BS)
Type: Binding_site

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .

This group of metallopeptidases belong to MEROPS peptidase family M24 (clan MG), subfamily M24A.

Methionine aminopeptidase (

) (MAP) is responsible for the removal of the amino-terminal (initiator) methionine from nascent eukaryotic cytosolic and cytoplasmic prokaryotic proteins if the penultimate amino acid is small and uncharged. All MAP studied to date are monomeric proteins that require cobalt ions for activity. Two subfamilies of MAP enzymes are known to exist . While being evolutionary related, they only share a limited amount of sequence similarity mostly clustered around the residues shown, in the Escherichia coli MAP , to be involved in cobalt-binding. The first family consists of enzymes from prokaryotes as well as eukaryotic MAP-1, while the second group (

) is made up of archaeal MAP and eukaryotic MAP-2 and includes proteins which do not seem to be MAP, but that are clearly evolutionary related such as mouse proliferation-associated protein 1 and fission yeast curved DNA-binding protein. This entry represents a cobalt binding site.
Transcription factor COE, conserved site (Transcription_factor_COE_CS)
Type: Conserved_site

The independent cloning of rodent EBF/Olf-1 and Drosophila melanogaster Collier has defined a family of transcription factors, the Collier or COE family . COE proteins have various functions in different organisms.
Snake toxin, conserved site (Snake_toxin_con_site)
Type: Conserved_site

Snake toxins belong to a family of proteins which groups short and long neurotoxins, cytotoxins and short toxins, as well as a other miscellaneous venom peptides. Most of these toxins act by binding to the nicotinic acetylcholine receptors in the postsynaptic membrane of skeletal muscles and prevent the binding of acetylcholine, thereby blocking the excitation of muscles.

Snake toxins are proteins that consist of sixty to seventy five amino acids. Among the invariant residues are eight cysteines all involved in disulphide bonds. The structure is small, disulphide-rich, nearly all β sheet. This entry represents a conserved site found in some snake toxins.
Transcription regulator, HTH DeoR-type, conserved site (Tscrpt_reg_HTH_DeoR_CS)
Type: Conserved_site

The deoR-type HTH domain is a DNA-binding, helix-turn-helix (HTH) domain of about 50-60 amino acids present in transcription regulators of the deoR family, involved in sugar catabolism. This family of prokaryotic regulators is named after the Escherichia coli protein DeoR, a repressor of the deo operon, which encodes nucleotide and deoxyribonucleotide catabolic enzymes. DeoR also negatively regulates the expression of nupG and tsx, a nucleoside-specific transport protein and a channel-forming protein, respectively.

DeoR-like transcription repressors occur in diverse bacteria as regulators of sugar and nucleoside metabolic systems. The effector molecules for deoR-like regulators are generally phosphorylated intermediates of the relevant metabolic pathway. The DNA-binding deoR-type HTH domain occurs usually in the N-terminal part. The C-terminal part can contain an effector-binding domain and/or an oligomerisation domain. DeoR occurs as an octamer, whilst glpR and agaR are tetramers. Several operators may be bound simultaneously, which could facilitate DNA looping .

It is worth noting that the DeoR in this entry is represented by the protein, UniProt P0ACK5, from E. coli. Not the DeoR, UniProt P39140, from Bacillus subtilis. Despite sharing the same name, these two proteins do not share protein sequence similarity .