SII-SWORD/CoKE huggingface dataset:
Urease, beta subunit-like (Urease_beta-like)
Type: Family

Urease is a nickel-dependent metalloenzyme that catalyses the hydrolysis of urea to form ammonia and carbon dioxide. Nickel-dependent ureases are found in bacteria, archaea, fungi and plants. Their primary role is to allow the use of external and internally-generated urea as a nitrogen source. The enzyme consists of three subunits, alpha, beta and gamma, which can exist as separate proteins or can be fused on a single protein chain. The α-β-γ heterotrimer forms multimers, mainly trimers. The large alpha subunit is the catalytic domain containing an active site with a bi-nickel centre complexed by a carbamylated lysine. The beta and gamma subunits play a role in subunit association to form the higher order trimers .

This entry represents the urease beta subunit and similar sequences mainly found in bacteria and fungi. In Helicobacter pylori, the gamma and beta subunits are fused and known (confusingly) as the alpha subunit.
Citrate synthase (Citrate_synthase)
Type: Family

Citrate synthase

is a member of a small family of enzymes that can directly form a carbon-carbon bond without the presence of metal ion cofactors. It catalyses the first reaction in the Krebs' cycle, namely the conversion of oxaloacetate and acetyl-coenzyme A into citrate and coenzyme A. This reaction is important for energy generation and for carbon assimilation. The reaction proceeds via a non-covalently bound citryl-coenzyme A intermediate in a 2-step process (aldol-Claisen condensation followed by the hydrolysis of citryl-CoA).

This entry represents types I and II citrate synthase enzymes, as well as the related enzymes 2-methylcitrate synthase and ATP citrate synthase. 2-methylcitrate (

) synthase catalyses the conversion of oxaloacetate and propanoyl-CoA into (2R,3S)-2-hydroxybutane-1,2,3-tricarboxylate and coenzyme A. This enzyme is induced during bacterial and fungal growth on propionate , while type II hexameric citrate synthase is constitutive . ATP citrate synthase (

) (also known as ATP citrate lyase) catalyses the MgATP-dependent, CoA-dependent cleavage of citrate into oxaloacetate and acetyl-CoA, a key step in the reductive tricarboxylic acid pathway of CO2 assimilation used by a variety of autotrophic bacteria and archaea to fix carbon dioxide . ATP citrate synthase is composed of two distinct subunits. In eukaryotes, ATP citrate synthase is a homotetramer of a single large polypeptide, and is used to produce cytosolic acetyl-CoA from mitochondrial produced citrate . This entry includes citrate synthase from Thermosulfidibacter takaii, which catalyses both citrate generation and citrate cleavage as it is part of a reversible tricarboxylic acid (TCA) cycle that can fix carbon dioxide autotrophically and may represent an ancestral mode of the conventional reductive TCA (rTCA) cycle .
Paramyxovirus nucleocapsid protein (Paramyx_ncap)
Type: Family

The nucleocapsid protein is referred to as NP. NP is is the major structural component of the nucleocapsid. The protein is approx. 58kDa. 2600 NP molecules go to tightly encapsidate the viral RNA. NP interacts with several other viral encoded proteins, all of which are involved in controlling replication: NP-NP, NP-P, NP-(PL), and NP-V .
Pectate lyase (Pec_lyase)
Type: Domain

Pectate lyase

is an enzyme involved in the maceration and soft rotting of plant tissue. Pectate lyase is responsible for the eliminative cleavage of pectate, yielding oligosaccharides with 4-deoxy-alpha-D-mann-4-enuronosyl groups at their non-reducing ends. The protein is maximally expressed late in pollen development. It has been suggested that the pollen expression of pectate lyase genes might relate to a requirement for pectin degradation during pollen tube growth .

The structure and the folding kinetics of one member of this family, pectate lyase C (pelC)1 from Erwinia chrysanthemi has been investigated in some detail . PelC contains a parallel β-helix folding motif. The majority of the regular secondary structure is composed of parallel β-sheets (about 30%). The individual strands of the sheets are connected by unordered loops of varying length. The backbone is then formed by a large helix composed of β-sheets. There are two disulphide bonds in pelC and 12 proline residues. One of these prolines, Pro220, is involved in a cis peptide bond. he folding mechanism of pelC involves two slow phases that have been attributed to proline isomerization.
NADH-quinone oxidoreductase subunit E-like (NuoE-like)
Type: Family

Respiratory-chain NADH dehydrogenase (

) (also known as complex I or NADH-ubiquinone oxidoreductase) is an oligomeric enzymatic complex located in the inner mitochondrial membrane which also seems to exist in the chloroplast and in cyanobacteria (as a NADH-plastoquinone oxidoreductase). Among the 25 to 30 polypeptide subunits of this bioenergetic enzyme complex there is one with a molecular weight of 24 Kd (in mammals), which is a component of the iron-sulfur (IP) fragment of the enzyme. It seems to bind a 2Fe-2S iron-sulfur cluster. The 24 Kd subunit is nuclear encoded, as a precursor form with a transit peptide in mammals, and in Neurospora crassa.

The 24 Kd subunit is highly similar to : Subunit E of Escherichia coli NADH-ubiquinone oxidoreductase (gene nuoE) and Subunit NQO2 of Paracoccus denitrificans NADH-ubiquinone oxidoreductase.
Bacterioferritin (Bacterioferritin)
Type: Family

Bacterioferritin (BFR; also known as cytochrome b1 or cytochrome b557) of Escherichia coli is an iron-storage protein consisting of 24 identical subunits that pack together to form a highly symmetrical, nearly spherical shell surrounding a central cavity of about 8 nm diameter . X-ray crystallographic studies have revealed a close structural similarity between BFR and the ferritins, a family of iron-storage proteins found in both eukaryotes and bacteria . Common to both ferritins and BFRs is a capacity to store large quantities of iron within their hollow interior, in the form of a hydrated ferric oxide mineral containing variable amounts of phosphate anion. However, a major difference between them is that BFR contains up 12 b-type haem groups, while ferritins, as isolated, do not contain haem.

The building block for the BFR shell is a protein dimer (subunits A and B) binding the single haem group. Each subunit consists of four nearly parallel α-helices. The haem is bound symmetrically to subunits A and B by Met(A)-52 and Met(B)-52 residues . Each subunit includes a binuclear metal-binding site linking together the four major helices of the subunit, which has been identified as the ferroxidase centre of BFR . The ferroxidase centre is where that initial oxidation of ferrous iron by molecular oxygen occurs, facilitating the detoxification of iron, protection against dioxygen and radical products, and storage of ferric-hydroxyphosphate at the core . BFR mutants with Met-52 replaced are haem-free, but appear to be correctly assembled and are capable of accumulating iron . Some bacterioferritins are composed of two subunit types, one conferring heme-binding ability (alpha) and the other (beta) bestowing ferroxidase activity .
Urease, gamma/gamma-beta subunit (Urease_gamma/gamma-beta_su)
Type: Family

Urease (urea amidohydrolase,

) is a nickel-dependent metalloenzyme that catalyses the hydrolysis of urea to form ammonia and carbon dioxide. Nickel-dependent ureases are found in bacteria, archaea, fungi and plants. Their primary role is to allow the use of external and internally-generated urea as a nitrogen source. The enzyme consists of three subunits, alpha, beta and gamma, which can exist as separate proteins or can be fused on a single protein chain. The α-β-γ heterotrimer forms multimers, mainly trimers. The subunit composition of urease from different sources varies , but each holoenzyme consists of four domains : three structural domains and a nickel-binding catalytic domain common to amidohydrolases .

In Klebsiella aerogenes, urease exists as an alpha, beta and gamma subunit, with the alpha subunit possessing the catalytic domain. In Helicobacter pylori, the gamma and beta subunits are fused and called the alpha subunit, while the catalytic subunit is called the beta subunit. In Canavalia ensiformis, urease has a fused gamma-beta-alpha organisation.

This entry represents the urease gamma subunit. It also identifies gamma subunits fused with other urease subunits, as found in Helicobacter and other species.
Tryptophan synthase, alpha chain (Trp_synthase_suA)
Type: Family

Tryptophan synthase (

) catalyses the last step in the biosynthesis of tryptophan :

L-serine + 1-(indol-3-yl)glycerol 3-phosphate = L-tryptophan + glyceraldehyde 3-phosphate + H
2
O

It has two functional domains, each found in bacteria and plants on a separate subunit. In Escherichia coli, the two subunits, A and B, are encoded by the trpA and trpB genes respectively. The alpha chain is for the aldol cleavage of indoleglycerol phosphate to indole and glyceraldehyde 3-phosphate and the beta chain

is for the synthesis of tryptophan from indole and serine. In fungi the two domains are fused together in a single multifunctional protein, in the order: (NH2-A-B-COOH) . The two domains of the Neurospora crassa polypeptide are linked by a connector of 54-amino acid residues that has less than 25% identity to the 45-residue connector of the Saccharomyces cerevisiae (Baker's yeast) polypeptide. Two acidic residues are believed to serve as proton donors/acceptors in the enzyme's catalytic mechanism.
Peptidase A22A, presenilin 1 (Pept_A22A_PS1)
Type: Family

This group of aspartic peptidases belong to MEROPS peptidase family A22 (presenilin family, clan AD): subfamily A22A, the type example being presenilin 1 from Homo sapiens (Human).

Presenilins are polytopic transmembrane (TM) proteins, mutations in which are associated with the occurrence of early-onset familial Alzheimer's disease, a rare form of the disease that results from a single-gene mutation . The physiological functions of presenilins are unknown, but they may be related to developmental signalling, apoptotic signal transduction, or processing of selected proteins, such as the beta-amyloid precursor protein(beta-APP). There are a number of subtypes which belong to this presenilin family. That presenilin homologues have been identified in species that do not have an Alzhemier's disease correlate suggests that they may have functions unrelated to the disease, homologues having been identified in Mus musculus (Mouse), Drosophila melanogaster, Caenorhabditis elegans and other members of the eukarya including plants.

Presenilin-1 (MEROPS identifer A22.001) has been identified as the gamma-secretase that performs one of the cleavages that leads to the release of the amyloid-beta peptide from its precursor protein. Processing of the amyloid beta precursor requires an initial cleavage by beta-secretase (now identified as BACE-1), which releases the extracellular domain, followed by cleavages by presenilin-1 to release the amyloid-beta peptide and an intracellular domain . Released amyloid-beta peptide can form the plaques that are depoited in the brains of patients suffering Alzheimer's disease . Presenilin-1 is a transmembrane peptidase in which the active site is buried in the membrane . Native presenilin-1 is processed in the large loop between the sixth and seventh transmembrane regions to form a two-chain protein, with a larger N-terminal domain . The heterodimer forms a complex with three other membrane proteins, nicastrin, Aph-1 and Pen-2 . In addition to the amyloid beta protein, presenilin-1 also cleaves Notch, various cadherins, Notch ligands Delta and Jagged, and other proteins .
Sec-independent periplasmic protein translocase TatC (TatC)
Type: Family

Proteins encoded by the mttABC operon (formerly yigTUW), mediate a novel Sec-independent membrane targeting and translocation system in Escherichia coli that interacts with cofactor-containing redox proteins having a S/TRRXFLK "twin arginine" leader motif. This family contains the E. coli mttB gene (TATC) .

A functional Tat system or Delta pH-dependent pathway requires three integral membrane proteins: TatA/Tha4, TatB/Hcf106 and TatC/cpTatC. The TatC protein is essential for the function of both pathways. It might be involved in twin-arginine signal peptide recognition, protein translocation and proton translocation. Sequence analysis predicts that TatC contains six transmembrane helices (TMHs), and experimental data confirmed that N and C termini of TatC or cpTatC are exposed to the cytoplasmic or stromal face of the membrane. The cytoplasmic N terminus and the first cytoplasmic loop region of the E. coli TatC protein are essential for protein export. At least two TatC molecules co-exist within each Tat translocon .
Alpha-isopropylmalate/homocitrate synthase, conserved site (AIPM/Hcit_synth_CS)
Type: Conserved_site

A number of enzymes have been shown to be functionally as well as evolutionary related . The nifV and leuA genes encode homocitrate synthase and alpha-isopropylmalate synthase, respectively The N-terminal parts of NifV and LeuA from bacteria are highly similar to each other . Homocitrate synthase (

) (gene nifV) is involved in the biosynthesis of the iron-molybdenum cofactor of nitrogenase and catalyzes the condensation of acetyl-CoA and alpha-ketoglutarate into homocitrate. Alpha-isopropylmalate synthase (

) catalyses the first step in the biosynthesis of leucine, the condensation ofacetyl-CoA and alpha-ketoisovalerate to form 2-isopropylmalate synthase.
von Willebrand factor, type A (VWF_A)
Type: Domain

The von Willebrand factor is a large multimeric glycoprotein found in blood plasma. Mutant forms are involved in the aetiology of bleeding disorders
. In von Willebrand factor, the type A domain (vWF) is the prototype for a protein superfamily. The vWF domain is found in various plasma proteins: complement factors B, C2, CR3 and CR4; the integrins (I-domains); collagen types VI, VII, XII and XIV; and other extracellular proteins . Although the majority of VWA-containing proteins are extracellular, the most ancient ones present in all eukaryotes are all intracellular proteins involved in functions such as transcription, DNA repair, ribosomal and membrane transport and the proteasome. A common feature appears to be involvement in multiprotein complexes. Proteins that incorporate vWF domains participate in numerous biological events (e.g. cell adhesion, migration, homing, pattern formation, and signal transduction), involving interaction with a large array of ligands . A number of human diseases arise from mutations in VWA domains.
Endoribonuclease YbeY (YbeY)
Type: Family

YbeY is a single strand-specific metallo-endoribonuclease involved in late-stage 70S ribosome quality control and in maturation of the 3' terminus of the 16S rRNA. It acts together with the RNase R to eliminate defective 70S ribosomes, but not properly matured 70S ribosomes or individual subunits, by a process mediated specifically by the 30S ribosomal subunit. It is involved in the processing of 16S, 23S and 5S rRNAs, with a particularly strong effect on maturation at both the 5'-and 3'-ends of 16S rRNA as well as maturation of the 5'-end of 23S and 5S rRNAs .

The crystal structure of the protein from the hyperthermophilic bacteria Aquifex aeolicus has been determined. The overall fold consists of one central α-helix surrounded by a four-stranded β-sheet and four other α-helices. Structure-based homology analysis reveals a good resemblance to the metal-dependent proteinases such as collagenases and gelatinases. However, experimental tests for collagenase and gelatinase-type function show no detectable activity under standard assay conditions .
Glycoside hydrolase, family 8 (Glyco_hydro_8)
Type: Family

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

Glycoside hydrolase family 8

comprises enzymes with several known activities; endoglucanase (

); lichenase (

); chitosanase (

). These enzymes were formerly known as cellulase family D .
Osteopontin (Osteopontin)
Type: Family

The major event of endochondrial ossification is the proteolytic degradation of calcified cartilage and the extracellular matrix, and their
substitution with bone-specific extracellular matrix produced and organised by osteoblasts . One of the most abundant products of osteoblasts is osteopontin, a glycosylated phosphoprotein with a high acidic amino acid content and one copy of the cell attachment sequence RGD . It is thought that osteopontin may act as a bridge between osteoblasts and the apatite mineral of the bone . Osteopontin-K is a kidney protein, similar to osteopontin and probably also involved in cell adhesion .
Uricase (Uricase)
Type: Family

Uricase (

) (urate oxidase) is the peroxisomal enzyme responsible for the degradation of urate into allantoin:

Urate + O
2
+ H
2
O = 5-hydroxyisourate + H
2
O
2

Some species, like primates and birds, have lost the gene for uricase and are therefore unable to degrade urate . Uricase is a protein of 300 to 400 amino acids, its sequence is well conserved. It is mainly localised in the liver, where it forms a large electron-dense paracrystalline core in many peroxisomes . The enzyme exists as a tetramer of identical subunits, each containing a possible type 2 copper-binding site . In legumes, 2 forms of uricase are found: in the roots, the tetrameric form; and, in the uninfected cells of root nodules, a monomeric form, which plays an important role in nitrogen-fixation .
Uracil-DNA glycosylase family 1 (UDG_fam1)
Type: Family

Uracil-DNA glycosylase

(UDG, UNG) is a DNA repair enzyme that excises uracil residues from DNA by cleaving the N-glycosylic bond. Uracil in DNA can arise as a result of mis-incorporation of dUMP residues by DNA polymerase or deamination of cytosine. UDGs were classified into 4 families .

Family 1 enzymes are active against uracil in both ssDNA and dsDNA, and recognise uracil explicitly in an extrahelical conformation via a combination of protein and bound-water interactions . Family 1 enzymes are present in Eubacteria, Eukarya and in some eukaryotic viruses. The sequence of uracil-DNA glycosylases is extremely well conserved in bacteria and eukaryotes as well as in herpes viruses . More distantly related uracil-DNA glycosylases are also found in poxviruses . In eukaryotic cells, UNG activity is found in both the nucleus and the mitochondria. Human nuclear UNG2 and mitochondrial UNG1are both encoded by the UNG gene . The N-terminal 77 amino acids of UNG1 seem to be required for mitochondrial localisation . The catalytic C-terminal domains of UNGs are highly conserved at both the sequence and structure level while the N-terminal domains are diverse and are thought to be involved in subcellular localisation and protein-protein interactions .
Carbohydrate binding module family 20 (CBM20)
Type: Domain

This entry represents

, which binds starch. The crystal structure of CBM20 has been solved . It consists of seven β-strands forming an open-sided distorted β-barrel. Several aromatic residues, especially the well-conserved Trp and Tyr residues, participate in granular starch binding.

A carbohydrate-binding module (CBM) is defined as a contiguous amino acid sequence within a carbohydrate-active enzyme with a discreet fold having carbohydrate-binding activity. A few exceptions are CBMs in cellulosomal scaffolding proteins and rare instances of independent putative CBMs. The requirement of CBMs existing as modules within larger enzymes sets this class of carbohydrate-binding protein apart from other non-catalytic sugar binding proteins such as lectins and sugar transport proteins.

CBMs were previously classified as cellulose-binding domains (CBDs) based on the initial discovery of several modules that bound cellulose . However, additional modules in carbohydrate-active enzymes are continually being found that bind carbohydrates other than cellulose yet otherwise meet the CBM criteria, hence the need to reclassify these polypeptides using more inclusive terminology.

Previous classification of cellulose-binding domains were based on amino acid similarity. Groupings of CBDs were called "Types" and numbered with roman numerals (e.g. Type I or Type II CBDs). In keeping with the glycoside hydrolase classification, these groupings are now called families and numbered with Arabic numerals. Families 1 to 13 are the same as Types I to XIII. For a detailed review on the structure and binding modes of CBMs see .
Metallothionein, crustacean (Metalthion_crustacean)
Type: Family

Metallothioneins (MT) are small proteins that bind heavy metals, such as zinc, copper, cadmium, nickel, etc. They have a high content of cysteine residues that bind the metal ions through clusters of thiolate bonds . An empirical classification into three classes has been proposed by Fowler and coworkers and Kojima . Members of class I are defined to include polypeptides related in the positions of their cysteines to equine MT-1B, and include mammalian MTs as well as from crustaceans and molluscs. Class II groups MTs from a variety of species, including sea urchins,
fungi, insects and cyanobacteria. Class III MTs are atypical polypeptides composed of gamma-glutamylcysteinyl units .

This original classification system has been found to be limited, in the sense that it does not allow clear differentiation of patterns of structural similarities, either between or within classes. Subsequently, a new classification was proposed on the basis of sequence similarity derived from phylogenetic relationships, which basically proposes an MT family for each main taxonomic group of organisms .

Crustacean MTs belong to family 3. They are small proteins, with 18 totally conserved cysteines. The members of this family are recognised by the sequence pattern P-[GD]-P-C-C-x(3,4)-C-x-C located at the Nterm. The taxonomic range of the members extends to crustaceans. Known characteristics of this family are: 58 to 60 AAs; variants exist with and without the N-terminal Met. Protein sequence is divided into two structural domains, containing each 9 Cys binding 3 bivalent metal ions. Family 3 includes subfamilies: c1, c2, c. All sequences are very similar. c1 and c2 are forming two distinct monophyletic groups in the AA phylogenetic tree. c are crustacean MTs different from c1 and c2 based on phylogenetic analyses.
Adipokinetic hormone, conserved site (Adipokinetic_hormone_CS)
Type: Conserved_site

Adipokinetic hormones (AKH) are small active peptides produced by some insect species. They bring on the release of diglycerides from the fat body and then stimulate the flight muscles to use them as an energy source. There are other types of active peptides structurally related to AKH. These peptides are eight to ten amino acid residues long.
EF-hand domain (EF_hand_dom)
Type: Domain

Many calcium-binding proteins belong to the same evolutionary family and share a type of calcium-binding domain known as the EF-hand. This type of domain consists of a twelve residue loop flanked on both sides by a twelve residue α-helical domain. In an EF-hand loop the calcium ion is coordinated in a pentagonal bipyramidal configuration. The six residues involved in the binding are in positions 1, 3, 5, 7, 9 and 12; these residues are denoted by X, Y, Z, -Y, -X and -Z. The invariant Glu or Asp at position 12 provides two oxygens for liganding Ca (bidentate ligand). Ca2 binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers .