SII-SWORD/CoKE huggingface dataset:
Phosphotransferase system EIIB, cysteine phosphorylation site (PTrfase_EIIB_Cys)
Type: Conserved_site

The phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS) is a major carbohydrate transport system in bacteria. The PTS catalyzes the phosphorylation of incoming sugar substrates concomitant with their translocation across the cell membrane. The general mechanism of the PTS is the following: a phosphoryl group from phosphoenolpyruvate (PEP) is transferred to enzyme-I (EI) of PTS which in turn transfers it to a phosphoryl carrier protein (HPr). Phospho-HPr then transfers the phosphoryl group to a sugar-specific permease which consists of at least three structurally distinct domains (IIA, IIB, and IIC) which can either be fused together in a single polypeptide chain or exist as two or three interactive chains, formerly called enzymes II (EII) and III (EIII).

The first domain (IIA) carries the first permease-specific phoshorylation site, a histidine, which is phosphorylated by phospho-HPr. The second domain (IIB) is phosphorylated by phospho-IIA on a cysteinyl or histidyl residue, depending on the permease. Finally, the phosphoryl group is transferred from the IIB domain to the sugar substrate in a process catalyzed by the IIC domain; this process is coupled to the transmembrane transport of the sugar.

This entry covers the phosphorylation site of EIIB domains.
Serine proteases, trypsin family, histidine active site (TRYPSIN_HIS)
Type: Active_site

This entry represents the histidine active site of serine proteases belonging to the MEROPS peptidase family S1 (chymotrypsin family, clan PA(S)). The catalytic activity of the serine proteases from the chymotrypsin family is provided by a charge relay system involving an aspartic acid residue hydrogen-bonded to a histidine, which itself is hydrogen-bonded to a serine. The sequences in the vicinity of the active site histidine residues are well conserved in this family of proteases .

The chymotrypsin family is almost totally confined to animals, although trypsin-like enzymes are found in actinomycetes of the genera Streptomyces and Saccharopolyspora, and in the fungus Fusarium oxysporum . The enzymes are inherently secreted, being synthesised with a signal peptide that targets them to the secretory pathway. Animal enzymes are either secreted directly, packaged into vesicles for regulated secretion, or are retained in leukocyte granules .
Somatotropin hormone, conserved site (Somatotropin_CS)
Type: Conserved_site

Somatotropin is a hormone that plays an important role in growth control. It belongs to a family that includes choriomammotropin (lactogen), its placental analogue; prolactin, which promotes lactation in the mammary gland, and placental prolactin-related proteins; proliferin and proliferin related protein; and somatolactin from various fish .
The 3D structure of bovine somatotropin has been predicted using a combination of heuristics and energy minimisation .
DNA methylase, C-5 cytosine-specific, active site (C5_DNA_meth_AS)
Type: Active_site

C-5 cytosine-specific DNA methylases (C5 Mtase) are enzymes that specifically methylate the C-5 carbon of cytosines in DNA . Such enzymes are found in the proteins described below.

As a component of type II restriction-modification systems in prokaryotes and some bacteriophages. Such enzymes recognise a specific DNA sequence where they methylate a cytosine. In doing so, they protect DNA from cleavage by type II restriction enzymes that recognise the same sequence. The sequences of a large number of type II C-5 Mtases are known.

In vertebrates, there are a number of C-5 Mtases that methylate CpG dinucleotides. The sequence of the mammalian enzyme is known.

C-5 Mtases share a number of short conserved regions. This conserved region contains a conserved Pro-Cys dipeptide in which the cysteine has been shown to be involved in the catalytic mechanism; it appears to form a covalent intermediate with the C6 position of cytosine .
Strictosidine synthase, conserved region (Strictosidine_synth_cons-reg)
Type: Domain

This entry represents a conserved region found in plant strictosidine synthase (

), a key enzyme in alkaloid biosynthesis. It catalyses the Pictet-Spengler stereospecific condensation of tryptamine with secologanin to form strictosidine . The structure of the native enzyme from the Indian medicinal plant Rauvolfia serpentina (Serpentwood) (Devilpepper) represents the first example of a six-bladed four-stranded β-propeller fold from the plant kingdom .

This region is also found in animal Adipocyte plasma membrane-associated proteins (APMAP). In human, APMAP exhibits strong arylesterase activity with beta-naphthyl acetate and phenyl acetate and may play a role in adipocyte differentiation .

A group of uncharacterised bacterial proteins also belongs to this group of proteins.
Glycoside hydrolase family 1, active site (Glyco_hydro_1_AS)
Type: Active_site

Glycoside hydrolase family 1

comprises enzymes with a number of known activities; beta-glucosidase (

); beta-galactosidase (

); 6-phospho-beta-galactosidase (

); 6-phospho-beta-glucosidase (

); lactase-phlorizin hydrolase (

)/(

); beta-mannosidase (

); myrosinase (

).

This entry represents a conserved region found in these enzymes. It is centred on a conserved glutamic acid residue which has been shown in the beta-glucosidase from Agrobacterium, to be directly involved in glycosidic bond cleavage by acting as a nucleophile.
Seven-in-absentia protein, TRAF-like domain (7-in-absentia-prot_TRAF-dom)
Type: Domain

This entry represents the C-terminal TRAF-like domain found in the seven in absentia (sina).

The seven in absentia (sina) is a RING-type E3 ubiquitin ligase first identified in Drosophila. The Drosophila Sina protein is essential for the determination of the R7 pathway in photoreceptor cell development: the loss of functional Sina results in the transformation of the R7 precursor cell to a non-neuronal cell type. The Sina protein contains an N-terminal RING finger domain C3HC4-type, through which it binds E2 ubiquitin-conjugating enzymes (UbcD1). Sina also interacts with Tramtrack (TTK88) via PHYL. Tramtrack is a transcriptional repressor that blocks photoreceptor determination, while PHYL down-regulates the activity of TTK88. In turn, the activity of PHYL requires the activation of the Sevenless receptor tyrosine kinase, a process essential for R7 determination. It is thought that Sina targets TTK88 for degradation, therefore promoting the R7 pathway. The remainder C-terminal part is involved in interactions with other proteins, and consists of two zinc fingers and a TRAF-like domain.

Murine and human homologues of Sina have also been identified, namely Siah1 and Siah2 . The human homologue Siah-1 also binds E2 enzymes (UbcH5) and through a series of physical interactions, targets beta-catenin for ubiquitin degradation. Siah-1 expression is enhanced by p53, itself promoted by DNA damage. Thus, this pathway links DNA damage to beta-catenin degradation .

In addition to the Drosophila protein and mammalian homologues, whose similarity was noted previously, this family also includes putative homologues from Caenorhabditis elegans, Arabidopsis thaliana .
Fork head domain conserved site1 (TF_fork_head_CS_1)
Type: Conserved_site

The fork head domain is a conserved domain of about 100 amino-acid residues found in some eukaryotic transcription factors. It is involved in DNA-binding . This entry represents a conserved site found in the N-terminal section of the fork head domain.
WWE domain, subgroup (WWE-dom_subgr)
Type: Domain

The WWE domain is named after three of its conserved residues and is predicted to mediate specific protein-protein interactions in ubiquitin and ADP ribose conjugation systems. This domain is found as a tandem repeat at the N-terminal of Deltex, a cytosolic effector of Notch signalling thought to bind the N-terminal of the Notch receptor . It is also found as an interaction module in protein ubiquination and ADP ribosylation proteins .
Small acid-soluble spore protein, alpha/beta-type, conserved site (SASP_alpha/beta-type_CS)
Type: Conserved_site

Small, acid-soluble spore proteins (SASP or ASSP) are proteins bound to the spore DNA of bacteria of the genera Bacillus, Thermoactynomycetes, and Clostridium . They are double-stranded DNA-binding proteins that cause DNA to change to an A-like conformation. They protect the DNA backbone from chemical and enzymatic cleavage and are thus involved in dormant spore's high resistance to UV light. SASP are degraded in the first minutes of spore germination and provide amino acids for both new protein synthesis and metabolism.

There are two distinct families of SASP: the α/β type and the gamma-type. Alpha/beta SASP are small proteins of about sixty to seventy amino acid residues that are generally coded by a multigene family. The N terminus of alpha/beta SASP contains the site which is cleaved by a SASP-specific protease that acts during germination while the C terminus and is probably involved in DNA-binding.
Phosphoenolpyruvate carboxylase, Lys active site (PEP_COase_Lys_AS)
Type: Active_site

Phosphoenolpyruvate carboxylase (PEPcase) catalyzes the irreversible β-carboxylation of phosphoenolpyruvate by bicarbonate to yield oxaloacetate and phosphate. The enzyme is found in all plants and in a variety of microorganisms. A histidine and a lysine have been implicated in the catalytic mechanism of this enzyme; the regions around these active site residues are highly conserved in PEPcase from various plants, bacteria and cyanobacteria.

This entry represents a conserved region containing the lysine active site.
Small ribosomal subunit protein uS2, conserved site (Ribosomal_uS2_CS)
Type: Conserved_site

Ribosomal protein uS2 is is a protein of 235 to 394 amino-acid residues and is one of the proteins from the small ribosomal subunit. uS2 belongs to a family of ribosomal proteins which, on the basis of sequence similarities , groups:

Eubacterial uS2.

Algal and plant chloroplast uS2.

Cyanelle uS2.

Archaebacterial uS2.

Higher eukaryotes P40 (previously thought to be a laminin receptor).

Yeast NAB1.

Plant mitochondrial uS2.

Yeast mitochondrial uS2 (also know as MRP4).
Restriction endonuclease, type II, EcoRI, Proteobacteria (Restrct_endonuc_II_EcoRI_Pbac)
Type: Family

This entry represents restriction endonucleases EcoRI in Proteobacteria, which requires magnesium as a cofactor. EcoRI recognises the DNA sequence GAATTC and cleaves after G-1 .
Lysosome-associated membrane glycoprotein, conserved site (LAMP_CS)
Type: Conserved_site

Lysosome-associated membrane glycoproteins (lamp) are integral membrane proteins, specific to lysosomes, and whose exact biological function is not yet clear. Structurally, the lamp proteins consist of two internally homologous lysosome-luminal domains separated by a proline-rich hinge region; at the C-terminal extremity there is a transmembrane region (TM) followed by a very short cytoplasmic tail (C). In each of the duplicated domains, there are two conserved disulphide bonds. This structure is schematically represented in the figure below.

+-----+ +-----+ +-----+ +-----+
| | | | | | | |
xCxxxxxCxxxxxxxxxxxxCxxxxxCxxxxxxxxxCxxxxxCxxxxxxxxxxxxCxxxxxCxxxxxxxx
+--------------------------++Hinge++--------------------------++TM++C+

In mammals, there are two closely related types of lamp: lamp-1 and lamp-2, which form major components of the lysosome membrane. In chicken lamp-1 is known as LEP100.

Also included in this entry is the macrophage protein CD68 (or macrosialin) is a heavily glycosylated integral membrane protein whose structure consists of a mucin-like domain followed by a proline-rich hinge; a single lamp-like domain; a transmembrane region and a short cytoplasmic tail.

There are two signatures in this entry, one is centred on the first conserved cysteine of the duplicated domains. The second corresponds to a region that includes the extremity of the second domain, the totality of the transmembrane region and the cytoplasmic tail.
Aconitase family, 4Fe-4S cluster binding site (Aconitase_4Fe-4S_BS)
Type: Binding_site

Aconitase (aconitate hydratase) is the enzyme from the tricarboxylic acid cycle that catalyzes the reversible isomerization of citrate and isocitrate. Cis-aconitate is formed as an intermediary product during the course of the reaction. In eukaryotes two isozymes of aconitase are known to exist: one found in the mitochondrial matrix and the other found in the cytoplasm. Aconitase, in its active form, contains a 4Fe-4S iron-sulphur cluster; three cysteine residues have been shown to be ligands of the 4Fe-4S cluster. It has been shown that the aconitase family also contains the following proteins:

Iron-responsive element binding protein (IRE-BP). IRE-BP is a cytosolic protein that binds to iron-responsive elements (IREs). IREs are stem-loop structures found in the 5'UTR of ferritin, and delta aminolevulinic acid synthase mRNAs, and in the 3'UTR of transferrin receptor mRNA.

3-isopropylmalate dehydratase (

) (isopropylmalate isomerase), the enzyme that catalyzes the second step in the biosynthesis of leucine.

Homoaconitase (

) (homoaconitate hydratase), an enzyme that participates in the alpha-aminoadipate pathway of lysine biosynthesis and that converts cis-homoaconitate into homoisocitric acid.

Esherichia coli protein YbhJ.

The signatures in this entry, identify the cysteine residues involved in the binding of the 4Fe-4S iron-sulphur cluster.
Nitrile hydratase, alpha subunit (Nitrile_hydratase_asu)
Type: Family

Nitrile hydratases (

) are bacterial enzymes that catalyse the hydration of nitrile compounds to the corresponding amides. They are used as biocatalysts in acrylamide production, one of the few commercial scale bioprocesses, as well as in environmental remediation for the removal of nitriles from waste streams. Nitrile hydratases are composed of two subunits, alpha and beta, and are normally active as a tetramer, α(2)β(2). Nitrile hydratases contain either a non-haem iron or a non-corrinoid cobalt centre, both types sharing a highly conserved peptide sequence in the alpha subunit (CXLCSC) that provides all the residues involved in coordinating the metal ion. Each type of nitrile hydratase specifically incorporated its metal with the help of activator proteins encoded by flanking regions of the nitrile hydratase genes that are necessary for metal insertion. The Fe-containing enzyme is photo-regulated: in the dark the enzyme is inactivated due to the association of nitric oxide (NO) to the iron, while in the light the enzyme is active by photo-dissociation of NO. The NO is held in place by a claw setting formed through specific oxygen atoms in two modified cysteines and a serine residue in the active site . The cobalt-containing enzyme is unaffected by NO, but was shown to undergo a similar effect with carbon monoxide . Fe-and cobalt-containing enzymes also display different inhibition patterns with nitrophenols.

Thiocyanate hydrolase (SCNase) is a cobalt-containing metalloenzyme with a cysteine-sulphinic acid ligand that hydrolyses thiocyanate to carbonyl sulphide and ammonia .

The two enzymes, nitrile hydratase and SCNase, are homologous over regions corresponding to almost the entire coding regions of the genes: the beta and alpha subunits of thiocyanate hydrolase were homologous to the amino-and carboxyl-terminal halves of the beta subunit of nitrile hydratase, and the gamma subunit of thiocyanate hydrolase was homologous to the alpha subunit of nitrile hydratase .

This entry represents the alpha subunit of both iron-and cobalt-containing nitrile hydratases; the alpha subunit is a duplication of two structural repeats, each consisting of 4 layers, α/β/β/α. It excludes the thiocyanate hydrolase gamma subunit of Thiobacillus thioparus, a sequence that appears to have evolved from within the family of nitrile hydratase alpha subunits but which differs by several indels and a more rapid accumulation of point mutations.
Somatostatin/Cortistatin, C-terminal (Somatostatin/Cortistatin_C)
Type: Domain

This entry represents the C-terminal region of somatostatin and cortistatin.
Folate receptor-like (Folate_rcpt-like)
Type: Domain

This entry represents a domain found in folate receptors and at the N terminus of hedgehog-interacting proteins. Folate receptors bind to folate and reduced folic acid derivatives and mediate delivery of 5-methyltetrahydrofolate to the interior of cells. These proteins are attached to the membrane by a GPI-anchor. A riboflavin-binding protein required for the transport of riboflavin to the developing oocyte in chicken also included in this entry.
CagE, TrbE, VirB component of type IV transporter system, central domain (CagE_TrbE_VirB_cntrl_dom)
Type: Domain

This domain is found in (amongst others): the Helicobacter pylori protein CagE (see examples), which together with other proteins from the cag pathogenicity island (PAI), encodes a type IV transporter secretion system. The precise role of CagE is not known, but studies in animal models have shown that it is essential for pathogenesis in Helicobacter pylori induced gastritis and peptic ulceration . Indeed, the expression of the cag PAI has been shown to be essential for stimulating human gastric epithelial cell apoptosis
in vitro
.
Glyoxalase I, conserved site (Glyoxalase_1_CS)
Type: Conserved_site

Glyoxalase I (lactoylglutathione lyase) catalyzes the first step of the glyoxal pathway in the following reaction:

glutathione + methylglyoxal = (R)-S-lactoylglutathione

S-lactoylglutathione is then converted by glyoxalase II to lactic acid . Glyoxalase I is a ubiquitous enzyme which binds one mole of zinc per subunit. The bacterial and yeast enzymes are monomeric while the mammalian one is homodimeric. The sequence of glyoxalase I is well conserved. In bacteria and mammals the enzyme is a protein of about 130 to 180 residues while in fungi it is about twice as long. In these organisms the enzyme is built out of the tandem repeat of a homologous domain.
Methylglyoxal synthase, active site (Methylglyoxal_synth_AS)
Type: Active_site

Methylglyoxal synthase (MGS) catalyses the conversion of dihydroxyacetone phosphate (DHAP) to methylglyoxal and phosphate:

Glycerone phosphate = methylglyoxal + phosphate

The first part of the catalytic mechanism is believed to be similar to TIM (triosephosphate isomerase) in that both enzymes utilise DHAP to form an ene-diolate phosphate intermediate. In MGS, the second catalytic step is characterised by the elimination of phosphate and collapse of the enediolate to form methylglyoxal instead of reprotonation to form the isomer glyceraldehyde 3-phosphate, as in TIM. This is the first reaction in the methylglyoxal bypass of the Embden-Myerhoff glycolytic pathway and is believed to provide physiological benefits under non-ideal growth conditions in bacteria . MGS is a small protein of about 13 to 17kDa. An aspartate residue is involved in the catalytic mechanism .

This entry represents a short conserved region that contains an aspartate residue involved in catalytic activty.
Lysyl-tRNA synthetase, class II, C-terminal (Lys-tRNA-synth_II_C)
Type: Domain

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .

Lysine-tRNA synthesis is catalysed by two unrelated families of tRNA ligases: class-I or class-II. In eubacteria and eukaryota lysine-tRNA ligases belong to class II, the same family as aspartyl tRNA ligase. The lysine-tRNA ligase class Ic family is present in archaea and some eubacteria . Moreover in some eubacteria there is a gene X, which is similar to a part of lysine-tRNA ligase from class II.

Lysine-tRNA ligase is duplicated in some species with, for example in Escherichia coli, as a constitutive gene (lysS) and an induced one (lysU). No residues are directly involved in catalysis, but a number of highly conserved amino acids and three metal ions coordinate the substrates and stabilise the pentavalent transition state. Lysine is activated by being attached to the alpha-phosphate of AMP before being transferred to the cognate tRNA. The refined crystal structures give "snapshots" of the active site corresponding to key steps in the aminoacylation reaction and provide the structural framework for understanding the mechanism of lysine activation. The active site of LysU is shaped to position the substrates for the nucleophilic attack of the lysine carboxylate on the ATP alpha-phosphate. No residues are directly involved in catalysis, but a number of highly conserved amino acids and three metal ions coordinate the substrates and stabilise the pentavalent transition state. A loop close to the catalytic pocket, disordered in the lysine-bound structure, becomes ordered upon adenine binding .
Transcription elongation factor, GreA/GreB, conserved site (TF_GreA/GreB_CS)
Type: Conserved_site

Bacterial proteins GreA and GreB , are related proteins of about 160 amino-acid residues, and are necessary for efficient RNA polymerase transcription elongation past template-encoded arresting sites. Arresting sites in DNA have the property of trapping a certain fraction of elongating RNA polymerases that pass through, resulting in locked DNA/RNA/ polymerase ternary complexes. Cleavage of the nascent transcript by cleavage factors, such as GreA or GreB, allows the resumption of elongation from the new 3'-terminus. GreA induces cleavage 2 or 3 nucleotides behind the terminus while GreB releases longer sequences up to 9 nucleotides in length.
Superoxide dismutase, copper/zinc, binding site (SOD_Cu/Zn_BS)
Type: Binding_site

Copper/Zinc superoxide dismutase (SODC) is one of the three forms of an enzyme that catalyzes the dismutation of superoxide radicals. SODC binds one atom each of zinc and copper. Various forms of SODC are known: a cytoplasmic form in eukaryotes, an additional chloroplast form in plants, an extracellular form in some eukaryotes, and a periplasmic form in prokaryotes. The metal binding sites are conserved in all the known SODC sequences .