SII-SWORD/CoKE huggingface dataset:
Dihydroxy-acid/6-phosphogluconate dehydratase, conserved site (DiOHA_6PGluconate_deHydtase_CS)
Type: Conserved_site

This entry represents two conserved sites: the first is located in the N-terminal half and contains a cysteine that could be involved in the binding of a 2Fe-2S iron-sulphur cluster; the second is located in the C-terminal half.

Two dehydratases, dihydroxy-acid dehydratase (

) (gene ilvD or ILV3) and 6-phosphogluconate dehydratase (

) (gene edd) have been shown to be evolutionary related . Dihydroxy-acid dehydratase catalyses the fourth step in the biosynthesis of isoleucine and valine, the dehydratation of 2,3-dihydroxy-isovaleic acid into alpha-ketoisovaleric acid. 6-Phosphogluconate dehydratase catalyses the first step in the Entner-Doudoroff pathway, the dehydratation of 6-phospho-D-gluconate into 6-phospho-2-dehydro-3-deoxy-D-gluconate. Another protein containing this signature is Escherichia coli YjhG, which has been identified as a D-xylonate dehydratase . The N-terminal part of the proteins contains a cysteine that could be involved in the binding of a 2Fe-2S iron-sulphur cluster .
Phosphoribosylglycinamide synthetase, conserved site (PRibGlycinamide_synth_CS)
Type: Conserved_site

Phosphoribosylglycinamide synthetase (

) (GARS) (phosphoribosylamine glycine ligase) catalyses the second step in the
de novo
biosynthesis of purine. The reaction catalysed by phosphoribosylglycinamide synthetase is the ATP-dependent addition of 5-phosphoribosylamine to glycine to form 5'phosphoribosylglycinamide:

ATP + 5-phosphoribosylamine + glycine = ADP + P
i
+ 5'-phosphoribosylglycinamide

In bacteria, GARS is a monofunctional enzyme (encoded by the purD gene). In yeast, GARS is part of a bifunctional enzyme (encoded by the ADE5,7 gene) in conjunction with phosphoribosylformylglycinamidine cyclo-ligase (AIRS) . In higher eukaryotes, GARS is part of a trifunctional enzyme in conjunction with AIRS and with phosphoribosylglycinamide formyltransferase (GART), forming GARS-AIRS-GART .

This signature pattern identifies a highly conserved octapeptide.
Phosphoribosylglycinamide synthetase, C-domain (PRibGlycinamide_synth_C-dom)
Type: Domain

Phosphoribosylglycinamide synthetase (

) (GARS) (phosphoribosylamine glycine ligase) catalyses the second step in the
de novo
biosynthesis of purine. The reaction catalysed by phosphoribosylglycinamide synthetase is the ATP-dependent addition of 5-phosphoribosylamine to glycine to form 5'phosphoribosylglycinamide:

ATP + 5-phosphoribosylamine + glycine = ADP + P
i
+ 5'-phosphoribosylglycinamide

In bacteria, GARS is a monofunctional enzyme (encoded by the purD gene). In yeast, GARS is part of a bifunctional enzyme (encoded by the ADE5,7 gene) in conjunction with phosphoribosylformylglycinamidine cyclo-ligase (AIRS) . In higher eukaryotes, GARS is part of a trifunctional enzyme in conjunction with AIRS and with phosphoribosylglycinamide formyltransferase (GART), forming GARS-AIRS-GART .

This entry represents the C-domain, which is related to the C-terminal domain of biotin carboxylase/carbamoyl phosphate synthetase (

).
Phosphoribosylglycinamide synthetase, ATP-grasp (A) domain (PRibGlycinamid_synth_ATP-grasp)
Type: Domain

Phosphoribosylglycinamide synthetase (

) (GARS) (phosphoribosylamine glycine ligase) catalyses the second step in the
de novo
biosynthesis of purine. The reaction catalysed by phosphoribosylglycinamide synthetase is the ATP-dependent addition of 5-phosphoribosylamine to glycine to form 5'phosphoribosylglycinamide:

ATP + 5-phosphoribosylamine + glycine = ADP + P
i
+ 5'-phosphoribosylglycinamide

In bacteria, GARS is a monofunctional enzyme (encoded by the purD gene). In yeast, GARS is part of a bifunctional enzyme (encoded by the ADE5,7 gene) in conjunction with phosphoribosylformylglycinamidine cyclo-ligase (AIRS) . In higher eukaryotes, GARS is part of a trifunctional enzyme in conjunction with AIRS and with phosphoribosylglycinamide formyltransferase (GART), forming GARS-AIRS-GART .

This entry represents the A-domain of the enzyme, and is related to the ATP-grasp domain of biotin carboxylase/carbamoyl phosphate synthetase.
Phosphoribosylglycinamide synthetase, N-terminal (PRibGlycinamide_synth_N)
Type: Domain

This entry represents the N-domain, which is related to the N-terminal domain of biotin carboxylase/carbamoyl phosphate synthetase (

).

Phosphoribosylglycinamide synthetase (

) (GARS) (phosphoribosylamine glycine ligase) catalyses the second step in the
de novo
biosynthesis of purine. The reaction catalysed by phosphoribosylglycinamide synthetase is the ATP-dependent addition of 5-phosphoribosylamine to glycine to form 5'phosphoribosylglycinamide:

ATP + 5-phosphoribosylamine + glycine = ADP + P
i
+ 5'-phosphoribosylglycinamide

In bacteria, GARS is a monofunctional enzyme (encoded by the purD gene). In yeast, GARS is part of a bifunctional enzyme (encoded by the ADE5,7 gene) in conjunction with phosphoribosylformylglycinamidine cyclo-ligase (AIRS) . In higher eukaryotes, GARS is part of a trifunctional enzyme in conjunction with AIRS and with phosphoribosylglycinamide formyltransferase (GART), forming GARS-AIRS-GART .
Crossover junction endodeoxyribonuclease RuvC, magnesium-binding site (X-over_junc_endoDNase_Mg_BS)
Type: Binding_site

The Escherichia coli RuvC gene is involved in DNA repair and in the late step of RecE and RecF pathway recombination . RuvC protein (

) cleaves cruciform junctions, which are formed by the extrusion of inverted repeat sequences from a super-coiled plasmid and which are structurally analogous to Holliday junctions, by introducing nicks into strands with the same polarity. The nicks leave a 5'terminal phosphate and a 3'terminal hydroxyl group which are ligated by E. coli or Bacteriophage T4 DNA ligases. Analysis of the cleavage sites suggests that DNA topology rather than a particular sequence determines the cleavage site. RuvC protein also cleaves Holliday junctions that are formed between gapped circular and linear duplex DNA by the function of RecA protein. The active form of RuvC protein is a dimer. This is mechanistically suited for an endonuclease involved in swapping DNA strands at the crossover junctions. It is inferred that RuvC protein is an endonuclease that resolves Holliday structures
in vivo
.

This signature pattern covers a region located in the C-terminal part of RuvC that contains two aspartate residues implicated in the binding of a magnesium ion required for function.
Imidazoleglycerol-phosphate dehydratase, conserved site (ImidazoleglycerP_deHydtase_CS)
Type: Conserved_site

Imidazoleglycerol-phosphate dehydratase (IGPD;

) catalyzes the dehydration of imidazole glycerol phosphate to imidazole acetol phosphate, the sixth step of histidine biosynthesis in plants and microorganisms where the histidine is synthesized de novo. There is an internal repeat in the protein domain that is related by pseudo-dyad symmetry, perhaps as a result of an ancient gene duplication. The apo-form of IGPD exists as a catalytically inactive trimer which, in the presence of specific divalent metal cations such as manganese (Mn2+), cobalt (Co2+), cadmium (Cd2+), nickel (Ni2+), iron (Fe2+) and zinc (Zn2+), assembles to form a biologically active high molecular weight metalloenzyme; a 24-mer with 4-3-2 symmetry. Each 24-mer has 24 active sites, and contains around 1.5 metal ions per monomer, each monomer contributing residues to three separate active sites.

IGPD enzymes are monofunctional in fungi, plants, archaea and some eubacteria while they are encoded as bifunctional enzymes in other eubacteria, such that the enzyme is fused to histidinol-phosphate phosphatase, the penultimate enzyme of the histidine biosynthesis pathway. The histidine biosynthesis pathway is a potential target for development of herbicides, and IGPD is a target for the triazole phosphonate herbicides .

Both signature patterns in this entry cover two consecutive, conserved histidine residues.
Histidine biosynthesis bifunctional protein HisB (His_synth_bifunc_HisB)
Type: Family

This entry represents the histidine biosynthesis bifunctional protein HisB , which contains an N-terminal histidinol phosphate phosphatase (

) and a C-terminal imidazoleglycerol-phosphate dehydratase (

) . HisB catalyses steps 6 and 8 of L-histidine biosynthesis. The N-terminal histidinol phosphate phosphatase domain folds into a single domain that has similarity to the haloacid dehalogenase (HAD) enzyme family, with a zinc ion stabilising the conformation of an extended loop .
Nodulation protein A, NodA, conserved site (Nodulation_prot_NodA_CS)
Type: Conserved_site

Rhizobial nodulation (Nod) factors are signalling molecules secreted by root-nodulating rhizobia in response to flavanoids excreted by the host plant. They induce various symbiotic responses on the roots of the leguminous host plant at low concentrations, and are required for successful infection . Nodulation factors are lipo-chitooligosaccharides made by bacterial nitrogen-fixing bacteria as a signal to plant hosts. Nod factors differ slightly from system to system and serve as host range determinants.

This signature pattern identifies a conserved region in the first third of the protein.
Ribosomal protein uS5 domain 2-type superfamily (Ribosomal_Su5_D2-typ_SF)
Type: Homologous_superfamily

The founding member of this superfamily is the second domain of the small ribosomal subunit protein uS5. This domain adopts α/β fold consisting of four-stranded mixed β-sheet and two helices packed on one side of it. Typical features for this superfamily are the psi-loop between strands 2 and 3; and the left-handed crossover between strands 3 and 4.

Domain 2 of the ribosomal protein uS5 has a left-handed, 2-layer α/β fold with a core structure consisting of β(3)-α-β-α. Domains with this fold are found in numerous RNA/DNA-binding proteins, as well as in kinases from the GHMP kinase family. Proteins containing this α/β fold domain include:

Translational machinery components (ribosomal proteins S5 and S9, and domain IV of elongation factors EF-G and eEF-2) .

Ribonuclease P protein (RNase P) .

Ribonuclease PH (domain 1) , as well as various exosome complex exonucleases (RRP41, RRP42, RRP43, RRP45, RRP46, MTR3, ECX1, ECX2) .

DNA modification proteins (DNA mismatch repair proteins MutL and PMS2, DNA gyrase B, DNA topoisomerase II, IV-B and VI-B) .

GHMP kinases that transfer a phosphoryl group from ATP to an acceptor (galactokinase (

), homoserine kinase (

), and mevalonate kinase (

)) .

Caenorhabditis elegans early switch protein Xol-1 (a divergent member of the GHMP kinase family that has lost the ATP-binding site) .

Hsp90 chaperone (middle domain), which is related to the DNA gyrase/MutL family ; this domain contains an extra C-terminal α/β subdomain.

Imidazole glycerol phosphate dehydratase, which contains a duplication consisting of two structural repeats of this fold .

The catalytic domain of ATP-dependent protease Lon (La), which contains an extra C-terminal α/β subdomain .

Formaldehyde-activating enzyme FAE, which contains a modification of this fold consisting of an extra α/β unit after strand 2 .
Uncharacterised protein family UPF0029, Impact, conserved site (UPF0029_Impact_CS)
Type: Conserved_site

This entry contains the protein Impact, which is a translational regulator that ensures constant high levels of translation under amino acid starvation. It acts by interacting with Gcn1/Gcn1L1, thereby preventing activation of Gcn2 protein kinases (EIF2AK1 to 4) and subsequent down-regulation of protein synthesis. It is evolutionary conserved from eukaryotes to archaea .
UDP-3-O-[3-hydroxymyristoyl] glucosamine N-acyltransferase, non-repeat region (UDP_GlcNAc_AcTrfase_non-rep)
Type: Domain

This entry represents the non-repeating region of the enzyme.

UDP-3-O-[3-hydroxymyristoyl] glucosamine N-acyltransferase (

) catalyses an early step in lipid A biosynthesis :
UDP-3-O-(3-hydroxytetradecanoyl)glucosamine + (R)-3-hydroxytetradecanoyl- [acyl carrier protein] = UDP-2,3-bis(3-hydroxytetradecanoyl)glucosamine + [acyl carrier protein]

This enzyme contains several hexapeptide repeats and forms part of the wider bacterial transferase hexapeptide repeat family.
Small ribosomal subunit protein uS9, conserved site (Ribosomal_uS9_CS)
Type: Conserved_site

This entry represents a conserved region, found in small ribosomal subunit protein uS9, containing many charged residues and located in the central section of these proteins.

uS9 proteins adopt a β/α/β fold similar to that found in numerous RNA/DNA-binding proteins, as well as in kinases from the GHMP kinase family .

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 .
Heat shock protein Hsp90, N-terminal (Hsp90_N)
Type: Domain

Prokaryotes and eukaryotes respond to heat shock and other forms of environmental stress by inducing synthesis of heat-shock proteins (hsp) . The 90kDa heat shock protein, Hsp90, is one of the most abundant proteins in eukaryotic cells, comprising 1-2% of cellular proteins under non-stress conditions . Its contribution to various cellular processes including signal transduction, protein folding, protein degradation and morphological evolution has been extensively studied . The full functional activity of Hsp90 is gained in concert with other co-chaperones, playing an important role in the folding of newly synthesised proteins and stabilisation and refolding of denatured proteins after stress. Apart from its co-chaperones, Hsp90 binds to an array of client proteins, where the co-chaperone requirement varies and depends on the actual client .

This entry represents the histidine kinase-like ATPase (HATPase) domain Hsp90 from eukaryotes and its bacterial homologues, known as HtpG (High temperature protein G).
Aminotransferase class-V, pyridoxal-phosphate binding site (Aminotrans_V_PyrdxlP_BS)
Type: Binding_site

Aminotransferases share certain mechanistic features with other pyridoxal- phosphate dependent enzymes, such as the covalent binding of the pyridoxal- phosphate group to a lysine residue. On the basis of sequence similarity, these various enzymes can be grouped into subfamilies. This entry represents the class V aminotransferases and the related, though functionally distinct, cysteine desulfurases.

This signature represents a conserved region surrounding the lysine residue that binds the pyridoxal-phosphate .
Exonuclease VII, large subunit, C-terminal (Exonuc_VII_lsu_C)
Type: Domain

Exonuclease VII (

) is composed of two nonidentical subunits; one large subunit and 4 small ones . Exonuclease VII catalyses exonucleolytic cleavage in either 5'-3' or 3'-5' direction to yield 5'-phosphomononucleotides. The large subunit also contains the OB-fold domains that bind to nucleic acids at the N terminus.

This entry represents Exonuclease VII, large subunit, C-terminal.
Glycine cleavage system P protein (GDC_P)
Type: Family

The P protein, also known as Glycine dehydrogenase (decarboxylating), is part of the glycine decarboxylase multienzyme complex (GDC), also annotated as glycine cleavage system or glycine synthase. GDC consists of four proteins P, H, L and T . The P protein (

) binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor, carbon dioxide is released and the remaining methylamin moiety is then transferred to the lipoamide cofactor of the H protein. The reaction catalysed by this protein is:

Glycine + lipoylprotein = S-aminomethyldihydrolipoylprotein + CO2

The subunit composition of glycine cleavage system P proteins have been classified into two types. Those from eukaryotes and some of the P proteins from prokaryotes (e.g. Escherichia coli) are in the homodimeric form. The rest of those from prokaryotes are heterotetrameric, with two different subunits which, based on sequence similarities, correspond respectively to the N and C-terminal halves of the eukaryotic subunit .
Inositol monophosphatase, metal-binding site (Inositol_monoP_metal-BS)
Type: Binding_site

This entry represents the metal-binding site found within the inositol monophosphatase family of proteins. It is suggested that these proteins may act by enhancing the synthesis or degradation of phosphorylated messenger molecules. The signature pattern of this entry contains the aspartic and threonine residues involved in binding a metal ion .

It has been shown that several proteins share two sequence motifs . Two of these proteins, vertebrate and plant inositol monophosphatase (

), and vertebrate inositol polyphosphate 1-phosphatase (

), are enzymes of the inositol phosphate second messenger signalling pathway, and share similar enzyme activity. Both enzymes exhibit an absolute requirement for metal ions (Mg2 is preferred), and their amino acid sequences contain a number of conserved motifs, which are also shared by several other proteins related to MPTASE (including products of fungal QaX and qutG, bacterial suhB and cysQ, and yeast hal2) . The function of the other proteins is not yet clear, but it is suggested that they may act by enhancing the synthesis or degradation of phosphorylated messenger molecules .

Structural analysis of these proteins has revealed a common core of 155 residues, which includes residues essential for metal binding and catalysis. An interesting property of the enzymes of this family is their sensitivity to Li+. The targets and mechanism of action of Li+ are unknown, but overactive inositol phosphate signalling may account for symptoms of manic depression .
DNA recombination/repair protein RecA, conserved site (DNA_recomb/repair_RecA_CS)
Type: Conserved_site

The recA gene product is a multifunctional enzyme that plays a role in homologous recombination, DNA repair and induction of the SOS response . In homologous recombination, the protein functions as a DNA-dependent ATPase, promoting synapsis, heteroduplex formation and strand exchange between homologous DNAs . RecA also acts as a protease cofactor that promotes autodigestion of the lexA product and phage repressors. The proteolytic inactivation of the lexA repressor by an activated form of recA may cause a derepression of the 20 or so genes involved in the SOS response, which regulates DNA repair, induced mutagenesis, delayed cell division and prophage induction in response to DNA damage .

RecA is a protein of about 350 amino acid residues. Its sequence is very well conserved among eubacterial species. It is also found in the chloroplast of plants . RecA-like proteins are found in archaea and diverse eukaryotic organisms, like fission yeast, mouse or human. In the filament visualised by X-ray crystallography, β-strand 3, the loop C-terminal to β-strand 2, and α-helix D of the core domain form one surface that packs against αa-helix A and β-strand 0 (the N-terminal domain) of an adjacent monomer during polymerisation . The core ATP-binding site domain is well conserved, with 14 invariant residues. It contains the nucleotide binding loop between β-strand 1 and α-helix C. The Escherichia coli sequence GPESSGKT matches the consensus sequence of amino acids (G/A)XXXXGK(T/S) for the Walker A box (also referred to as the P-loop) found in a number of nucleoside triphosphate (NTP)-binding proteins. Another nucleotide binding motif, the Walker B box is found at β-strand 4 in the RecA structure. The Walker B box is characterised by four hydrophobic amino acids followed by an acidic residue (usually aspartate). Nucleotide specificity and additional ATP-binding interactions are contributed by the amino acid residues at β-strand 2 and the loop C-terminal to that strand, all of which are greater than 90% conserved among bacterial RecA proteins.

This signature pattern is specific for the bacterial and chloroplastic RecA protein, and covers the most conserved region within these proteins, namely a nonapeptide located in the middle of the sequence and which is part of the monomer-monomer interface in a recA filament.
Photosystem I PsaA/PsaB, conserved site (PSI_PsaA/B_CS)
Type: Conserved_site

Photosystem I (PSI) is an integral membrane protein complex that uses light energy to mediate electron transfer from plastocyanin to ferredoxin. PSI is found in the chloroplast of plants and cyanobacteria. The electron transfer components of the reaction centre of PSI are a primary electron donor P-700 (chlorophyll dimer) and five electron acceptors: A0 (chlorophyll), A1 (a phylloquinone) and three 4Fe-4S iron-sulphur centres: Fx, Fa, and Fb.

PsaA and psaB, two closely related proteins, are involved in the binding of P700, A0, A1, and Fx. psaA and psaB are both integral membrane proteins of 730 to 750 amino acids that seem to contain 11 transmembrane segments. The Fx 4Fe-4S iron-sulphur centre is bound by four cysteines; two of these cysteines are provided by the psaA protein and the two others by psaB. The two cysteines in both proteins are proximal and located in a loop between the ninth and tenth transmembrane segments. A leucine zipper motif seems to be present downstream of the cysteines and could contribute to dimerisation of psaA/psaB.

This entry represents a conserved region that includes the two iron-sulphur binding cysteines.