SII-SWORD/CoKE huggingface dataset:
Molybdopterin dehydrogenase, FAD-binding (Mopterin_DH_FAD-bd)
Type: Domain

Oxidoreductases, that also bind molybdopterin, have essentially no similarity outside this common domain.
They include aldehyde oxidase (

), that converts an aldehyde and water to an acid and hydrogen peroxide, and xanthine dehydrogenase (

), that converts xanthine to urate. These enzymes require molybdopterin and FAD as cofactors and have and two 2FE-2S clusters. Another enzyme that contains this domain is the Pseudomonas thermocarboxydovorans carbon monoxide oxygenase and nicotine dehydrogenase involved in the degradation of nicotine.
Short-chain dehydrogenase/reductase SDR (SDR_fam)
Type: Family

The short-chain dehydrogenases/reductases family (SDR) is a very large family of enzymes, most of which are known to be NAD- or NADP-dependent oxidoreductases. As the first member of this family to be characterised was Drosophila alcohol dehydrogenase, this family used to be called 'insect-type', or 'short-chain' alcohol dehydrogenases. Most members of this family are proteins of about 250 to 300 amino acid residues. Most dehydrogenases possess at least 2 domains , the first binding the coenzyme, often NAD, and the second binding the substrate. This latter domain determines the substrate specificity and contains amino acids involved in catalysis. Little sequence similarity has been found in the coenzyme binding domain although there is a large degree of structural similarity, and it has therefore been suggested that the structure of dehydrogenases has arisen through gene fusion of a common ancestral coenzyme nucleotide sequence with various substrate specific domains .
Kazal domain (Kazal_dom)
Type: Domain

This entry represents the Kazal domain.

Canonical serine proteinase inhibitors are distributed in a wide range of organisms from all kingdoms of life and play crucial role in various physiological mechanisms . They interact from the canonical proteinase-inhibitor binding loop, where P1 residue has a predominant role (the residue at the P1 position contributing the carbonyl portion to the reactive-site peptide bond). These so-called canonical inhibitors bind to their cognate enzymes in the same manner as a good substrate, but are cleaved extremely slowly. Kazal-type inhibitors represent the most studied canonical proteinase inhibitors. Kazal inhibitors are extremely variable at their reactive sites. However, some regularity prevails such as the presence of lysine at position P1 indicating strong inhibition of trypsin .

The Kazal inhibitor has six cysteine residues engaged in disulfide bonds arranged as shown in the following schematic representation:

+------------------+
| |
*******************|***
xxxxxxxxCxxxxxxCx#xxxxxCxxxxxxxxxxCxxCxxxxxxxxxxxxxxxxxC
| | | |
| +-------------|-----------------+
+----------------------------+

'C': conserved cysteine involved in a disulfide bond.
'#': active site residue.
'*': position of the pattern.

The structure of classical Kazal domains consists of a central α-helix, which is inserted between two β-strands and a third that is toward the C terminus . The reactive site P1 and the conformation of the reactive site loop is structurally highly conserved, similar to the canonical conformation of small serine proteinase inhibitors.
Nitrophorin domain (Nitrophorin_domain)
Type: Domain

Nitrophorins are haemoproteins found in saliva of blood-feeding insects . Saliva of the blood-sucking bug Rhodnius prolixus (Triatomid bug) contains four homologous nitrophorins, designated NP1 to NP4 in order of their relative abundance in the glands . As isolated, nitrophorins contain nitric oxide (NO) ligated to the ferric (FeIII) haem iron. Histamine, which is released by the host in response to tissue damage, is another nitrophorin ligand. Nitrophorins transport NO to the feeding site. Dilution, binding of histamine and increase in pH (from pH ~5 in salivary gland to pH ~7.4 in the host tissue) facilitate the release of NO into the tissue where it induces vasodilatation.

The salivary nitrophorin from the hemipteran Cimex lectularius (Bed bug) has no sequence similarity to R. prolixus nitrophorins. It is suggested that the two classes of insect nitrophorins have arisen as a product of the convergent evolution .

3-D structures of several nitrophorin complexes are known . The nitrophorin structures reveal lipocalin-like eight-stranded β-barrel, three α-helices and two disulphide bonds, with haem inserted into one end of the barrel. Members of the lipocalin family are known to bind a variety of small hydrophobic ligands, including biliverdin, in a similar fashion (see for review). The haem iron is ligated to His59. The position of His59 is restrained through water-mediated hydrogen bond to the carboxylate of Asp70. The His59-Fe bond is bent ~15 degrees out of the imidazole plane. Asp70 forms an unusual hydrogen bond with one of the haem propionates, suggesting the residue has an altered pKa. In NP1-histamine structure, the planes of His59 and histamine imidazole rings lie in an arrangement almost identical to that found in oxidised cytochrome b5.

This entry represents the nitrophorin structural domain.
Eosinophil major basic protein (Eosinophil_major_basic)
Type: Family

Eosinophil granule major basic protein (MBP) is a low molecular weight cationic protein present in the crystalloid core of the eosinophil granule . It is a potent toxin for helminths and mammalian cells, and may have important roles in allergic and inflammatory reactions, it can release histamine from mast cells and damage epithelial cells of bronchial tubes. MBP is also involved in antiparasitic defence mechanisms and immune hypersensitivity reactions. The protein is a single arginine-rich polypeptide , its pro-portion being rich in glutamic and aspartic acids. It has been suggested that the protein is translated as a nontoxic precursor that protects the eosinophil from damage while it is processed through the endoplasmic reticulum to its sequestered site in the granule core toxic MBP . The sequence of MBP has been shown to contain a C-type lectin (CTL) domain . CTL domains are 110-130 residue motifs that appear to function as calcium-dependent carbohydrate-recognition domains .
Type-2 ice-structuring protein (AntifreezeII)
Type: Family

Marine teleosts from polar oceans can be protected from freezing in icy sea-water by serum antifreeze proteins (AFPs) or glycoproteins (AFGPs) . These function by binding to, and preventing the growth of, ice crystals within the fish. Despite functional similarity, the proteins are structurally diverse and include glycosylated and at least 3 non-glycosylated forms: the AFGP of nototheniids and cod are polymers of a tripeptide repeat, Ala-Ala-Thr, with a disaccharide attached to the threonine residue; type I AFPs are Ala-rich, α-helical peptides found in flounder and sculpin; type II AFPs of sea-raven, smelt and herring are Cys-rich proteins; and type III AFPs, found in Eel pouts, are rich in β-structure. Although no direct structural information is available for type II AFPs, their sequences are similar to the carbohydrate recognition domain (CRD) of Ca
2+
-dependent lectins. This domain is present in a superfamily of proteins that bind sugars specifically through contact with a calcium ion. The extent of similarity within the superfamily is confined to short motifs and single amino acids at intervals throughout the protein.
Interleukin-4 (IL-4)
Type: Family

Cytokines are protein messengers that carry information from cell to cell . Interleukin is one such molecule, and participates in several B-cell activation processes: e.g., it enhances production and secretion of IgG1 and IgE ; it induces expression of class II major histocompatability complex (MHC) molecules on resting B-cells; and it regulates expression of the low affinity Fc receptor for IgE on lymphocytes and monocytes. Interleukin-4 (IL4), which this entry represents, has a compact, globular fold (similar to other cytokines), stabilised by 3 disulphide bonds . One half of the structure is dominated by a 4 α-helix bundle with a left-handed twist . The helices are anti-parallel, with 2 overhand connections, which fall into a 2-stranded anti-parallel β-sheet .
Multicopper oxidase, copper-binding site (Cu_oxidase_Cu_BS)
Type: Binding_site

The entry represents a conserved region containing the Cu-binding site found in multicopper oxidases.

Multicopper oxidases oxidise their substrate by accepting electrons at a mononuclear copper centre and transferring them to a trinuclear copper centre; dioxygen binds to the trinuclear centre and, following the transfer of four electrons, is reduced to two molecules of water . There are three spectroscopically different copper centres found in multicopper oxidases: type 1 (or blue), type 2 (or normal) and type 3 (or coupled binuclear) . Multicopper oxidases consist of 2, 3 or 6 of these homologous domains, which also share homology to the cupredoxins azurin and plastocyanin. Structurally, these domains consist of a cupredoxin-like fold, a β-sandwich consisting of 7 strands in 2 β-sheets, arranged in a Greek-key β-barrel . Multicopper oxidases include:

Ceruloplasmin (

) (ferroxidase), a 6-domain enzyme found in the serum of mammals and birds that oxidizes different inorganic and organic substances; exhibits internal sequence homology that appears to have evolved from the triplication of a Cu-binding domain similar to that of laccase and ascorbate oxidase.

Laccase (

) (urishiol oxidase), a 3-domain enzyme found in fungi and plants, which oxidizes different phenols and diamines. CueO is a laccase found in Escherichia coli that is involved in copper-resistance .

Ascorbate oxidase (

), a 3-domain enzyme found in higher plants.

Nitrite reductase (

), a 2-domain enzyme containing type-1 and type-2 copper centres .
Large ribosomal subunit protein uL6, conserved site (Ribosomal_uL6_CS)
Type: Conserved_site

This entry represents a conserved region of the large ribosomal subunit protein uL6 previously known as ribosomal protein L6. In Escherichia coli, L6 is known to bind directly to the 23S rRNA and is located at the aminoacyl-tRNA binding site of the peptidyltransferase centre. It belongs to a family of ribosomal proteins, which on the basis of sequence similarities groups: bacterial, algal chloroplast, cyanelle, archaeal, Marchantia polymorpha mitochondrial L6, yeast mitochondrial YmL6 (gene MRPL6), mammalian, Drosophila melanogaster; plant and yeast L9 . This entry includes uL6 proteins from bacteria and some eukaryotes, while uL6 proteins from other organisms are found in

.

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 .
Large ribosomal subunit protein uL6, conserved site-2 (Ribosomal_uL6_CS2)
Type: Conserved_site

This entry represents a conserved region found in the large ribosomal subunit protein uL6 from archaea (previously known as ribosomal protein L6) and some eukaryotic species (in which this proteins is also called L9) . In Escherichia coli, L6 is known to bind directly to the 23S rRNA and is located at the aminoacyl-tRNA binding site of the peptidyltransferase centre. It belongs to a family of ribosomal proteins, which on the basis of sequence similarities groups: bacterial, algal chloroplast, cyanelle, archaeal, Marchantia polymorpha mitochondrial L6, yeast mitochondrial YmL6 (gene MRPL6), mammalian, Drosophila melanogaster, plant and yeast L9 . uL6 proteins from other organisms are found in

.

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 .
Antenna complex, alpha subunit conserved site (Antenna_alpha_CS)
Type: Conserved_site

This entry represents a conserved site found in the alpha subunit which includes the conserved histidine residue.

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.
Light-harvesting protein B beta chain (LHB-1/5)
Type: Family

This family represents the Light-harvesting protein B (also known as Antenna pigment protein) beta chain.

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.
Large ribosomal subunit protein uL10, conserved site, bacteria (Ribosomal_uL10_CS_bac)
Type: Conserved_site

This entry represents a conserved region located in the N-terminal section of the Large ribosomal subunit protein uL10, previously known as Ribosomal protein L10. This protein of 162 to 185 amino-acid residues is found in bacteria.

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 .
Terpene synthase, conserved site (Terpene_synthase_CS)
Type: Conserved_site

Several enzymes catalyse mechanistically related reactions which involve the highly complex cyclic rearrangement of squalene or its 2,3 oxide. Lanosterol synthase (

) (oxidosqualene--lanosterol cyclase) catalyzes the cyclization 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 catalyzes the cyclization of (S)-2,3-epoxysqualene to cycloartenol, and hopene synthase (

) (squalene--hopene cyclase), is a bacterial enzyme that catalyzes the cyclization of squalene into hopene, a key step in hopanoid (triterpenoid) metabolism. These enzymes are evolutionary related proteins of about 70 to 85 kD. This highly conserved region is rich in aromatic residues and is located in the C-terminal section.
Alpha-defensin, N-terminal (Alpha-defensin_N)
Type: Domain

This entry represents the N-terminal domain of a group of alpha defensins and similar sequences mainly found in mammals.

Defensins are 2-6kDa, cationic, microbicidal peptides active against many Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses containing three pairs of intramolecular disulphide bonds. On the basis of their size and pattern of disulphide bonding, mammalian defensins are classified into alpha, beta and theta categories. Alpha-defensins, which have been identified in humans, monkeys and several rodent species, are particularly abundant in neutrophils, certain macrophage populations and Paneth cells of the small intestine.

Defensins are produced constitutively and/or in response to microbial products or proinflammatory cytokines. Some defensins are also called corticostatins (CS) because they inhibit corticotropin-stimulated corticosteroid production. The mechanism(s) by which microorganisms are killed and/or inactivated by defensins is not understood completely. However, it is generally believed that killing is a consequence of disruption of the microbial membrane. The polar topology of defensins, with spatially separated charged and hydrophobic regions, allows them to insert themselves into the phospholipid membranes so that their hydrophobic regions are buried within the lipid membrane interior and their charged (mostly cationic) regions interact with anionic phospholipid head groups and water. Subsequently, some defensins can aggregate to form `channel-like' pores; others might bind to and cover the microbial membrane in a `carpet-like' manner. The net outcome is the disruption of membrane integrity and function, which ultimately leads to the lysis of microorganisms. Some defensins are synthesised as propeptides which may be relevant to this process.

Human neutrophil-derived alpha-defensins (HNPs) are capable of enhancing phagocytosis by mouse macrophages. HNP1-3 have been reported to increase the production of tumor necrosis factor (TNF) and IL-1, while decreasing the production of IL-10 by monocytes. Increased levels of proinflammatory factors (e.g. IL-1, TNF, histamine and prostaglandin D2) and suppressed levels of IL-10 at the site of microbial infection are likely to amplify local inflammatory responses. This might be further reinforced by the capacity of some human and rabbit alpha-defensins to inhibit the production of immunosuppressive glucocorticoids by competing for the binding of adrenocorticotropic hormone to its receptor. Moreover, human alpha-defensins can enhance or suppress the activation of the classical pathway of complement in vitro by binding to solid-phase or fluid-phase complement C1q, respectively. The capacity of defensins to enhance phagocytosis, promote neutrophil recruitment, enhance the production of proinflammatory cytokines, suppress anti-inflammatory mediators and regulate complement activation argues that defensins upregulate innate host inflammatory defences against microbial invasion.