SII-SWORD/CoKE huggingface dataset:
Nitrite/sulphite reductase iron-sulphur/sirohaem-binding site (NO2/SO3_Rdtase_FeS/sirohaem_BS)
Type: Binding_site

Nitrite reductases and bacterial sulphite reductases catalyse the 6-electron reduction of nitrite (sulphite) to ammonia (sulphide) . On the basis of physiological function, 2 types of nitrite reductase can be defined: the assimilatory type, which is involved in nitrate assimilation (denitrification); and the dissimilatory type, which is responsible for nitrate respiration function. Assimilatory nitrite reductases contain a prosthetic group termed sirohaem (an iron tetra-hydroporphyrin of the isobacteriochlorin type, with 8 carboxylic acid-containing peripheral sidechains), and an iron-sulphur cluster. Similarly, there are 2 types of sulphite reductase: the assimilatory type, which participate in the synthesis of sulphur-containing compounds; and the dissimilatory type, which are terminal reductases in the reduction of sulphate. Assimilatory sulphite reductases can catalyse 6-electron reduction without the formation of free intermediates, while dissimilatory reductases can produce trithionate and thiosulphate in addition to sulphide. Both types of reductase contain sirohaem and iron-sulphur clusters. A region of sequence similarity, about 80 amino acids long, is shared by assimilatory nitrite and sulphite reductases . Four conserved Cys residues are suggested to be involved in binding the sirohaem group and/or the iron-sulphur centre .
Nitrite/sulphite reductase 4Fe-4S domain (NO2/SO3_Rdtase_4Fe4S_dom)
Type: Domain

Sulphite reductases (SiRs) and related nitrite reductases (NiRs) catalyse the six-electron reduction reactions of sulphite to sulphide, and nitrite to ammonia, respectively. The Escherichia coli SiR enzyme is a complex composed of two proteins, a flavoprotein alpha-component (SiR-FP) and a hemoprotein beta-component (SiR-HP) (

), and has an α(8)β(4) quaternary structure . SiR-FP contains both FAD and FMN, while SiR-HP contains a Fe(4)S(4) cluster coupled to a siroheme through a cysteine bridge. Electrons are transferred from NADPH to FAD, and on to FMN in SiR-FP, from which they are transferred to the metal centre of SiR-HP, where they reduce the siroheme-bound sulphite.

SiR-HP has a two-fold symmetry, which generates a distinctive three-domain α/β fold that controls assembly and reactivity . In the E. coli SiR-HP enzyme (

), the iron is bound to cysteine residues at positions 433, 439, 478 and 482, the latter also forming the siroheme ligand.
Cation-transporting P-type ATPase, C-terminal (ATPase_P-typ_cation-transptr_C)
Type: Domain

This entry represents the conserved C-terminal region found in several classes of cation-transporting P-type ATPases, including those that transport H
+
(

), Na
+
(

), Ca
2+
(

), Na
+
/K
+
(

), and H
+
/K
+
(

). In the H
+
/K
+
-and Na
+
/K
+
-exchange P-ATPases, this domain is found in the catalytic alpha chain.

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

P-ATPases (also known as E1-E2 ATPases) (

) are found in bacteria and in a number of eukaryotic plasma membranes and organelles . P-ATPases function to transport a variety of different compounds, including ions and phospholipids, across a membrane using ATP hydrolysis for energy. There are many different classes of P-ATPases, which transport specific types of ion: H
+
, Na
+
, K
+
, Mg
2+
, Ca
2+
, Ag
+
and Ag
2+
, Zn
2+
, Co
2+
, Pb
2+
, Ni
2+
, Cd
2+
, Cu
+
and Cu
2+
. P-ATPases can be composed of one or two polypeptides, and can usually assume two main conformations called E1 and E2.
Threonylcarbamoyl-AMP synthase-like domain (Sua5-like_dom)
Type: Domain

This domain has been shown to bind preferentially to dsRNA . This domain is found in Sua5 (

) and carbamoyltransferase HypF. The Sua5 family is required for the formation of threonylcarbamoyladenosine in tRNA . Sua5 has been shown to be required for translational regulation and telomere recombination in yeast .
Odorant/pheromone binding protein, Lepidoptera (Odorant/phero-bd_Lep)
Type: Family

Pheromone binding proteins (PBPs) are abundant, secreted antennal proteins present in olfactory sensilla. They lie in the lymph that surrounds the dendrites of olfactory receptor neurons . The olfactory receptors of terrestrial animals exist in an aqueous environment, yet detect odorants that are primarily hydrophobic. The aqueous solubility of hydrophobic odorants is thought to be greatly enhanced via odorant binding proteins which exist in the extracellular fluid surrounding the odorant receptors . This family is composed of pheromone binding proteins (PBP), which are male-specific and associate with pheromone-sensitive neurons and general-odorant binding proteins (GOBP). GOBPs have been found in moth antennae, and share a high level of sequence similarity with the PBPs. They are believed to carry odorants rather than pheromones. This family is distinct from the vertebrate odorant-binding proteins (OBPs).
GTP binding domain (GTP-bd)
Type: Domain

Several proteins have recently been shown to contain the 5 structural motifs characteristic of GTP-binding proteins . These include murine DRG protein; GTP1 protein from Schizosaccharomyces pombe; OBG protein from Bacillus subtilis ; ferrous iron transport protein B and several others.
GTP1/OBG, conserved site (GTP1-OBG_CS)
Type: Conserved_site

A widespread family of GTP-binding proteins has been recently characterised . The function of the proteins that belong to this family is not yet known. They are polypeptides of about 40 to 48kDa which contain the five small sequence elements characteristic of GTP-binding proteins . As a signature pattern was selected the region that correspond to the ATP/GTP B motif (also called G-3 in GTP-binding proteins).
Aspartyl/Glutamyl-tRNA(Gln) amidotransferase, subunit B/E, catalytic (Asn/Gln-tRNA_Trfase_suB/E_cat)
Type: Domain

Glutamyl-tRNA(Gln) amidotransferase subunit B (

) is a microbial enzyme that furnishes a means for formation of correctly charged Gln-tRNA(Gln) through the transamidation of misacylated Glu-tRNA(Gln) in organisms which lack glutaminyl-tRNA synthetase. The reaction takes place in the presence of glutamine and ATP through an activated gamma-phospho-Glu-tRNA(Gln). The enzyme is composed of three subunits: A (an amidase), B and C. It also exists in eukaryotes as a protein targeted to the mitochondria.
Vinculin/alpha-catenin (Vinculin/catenin)
Type: Family

Vinculin is a eukaryotic protein that seems to be involved in the attachment of the actin-based microfilaments to the plasma membrane. Vinculin is located at the cytoplasmic side of focal contacts or adhesion plaques . In addition to actin, vinculin interacts with other structural proteins such as talin and alpha-actinins.

Vinculin is a large protein of 116kDa (about a 1000 residues). Structurally the protein consists of an acidic N-terminal domain of about 90kDa separated from a basic C-terminal domain of about 25kDa by a proline-rich region of about 50 residues. The central part of the N-terminal domain consists of a variable number (3 in vertebrates, 2 in Caenorhabditis elegans) of repeats of a 110 amino acids domain.

Alpha-catenins are proteins of about 100kDa which are evolutionary related to vinculin . Catenins are proteins that associate with the cytoplasmic domain of a variety of cadherins. The association of catenins to cadherins produces a complex which is linked to the actin filament network, and which seems to be of primary importance for cadherins cell-adhesion properties. Three different types of catenins seem to exist: alpha, beta, and gamma. In terms of their structure the most significant differences are the absence, in alpha-catenin, of the repeated domain and of the proline-rich segment.
Lantibiotic, Type A, Bacillales-type (Lantibiotic_typ-A_Bacillales)
Type: Family

Lantibiotics are heavily-modified bacteriocin-like peptides from Gram-positive bacteria. They contain alpha,beta-unsaturated amino acids (dehydroalanine and dehydrobutyrine) and lanthionine or 3-methyllanthionine rings (collectively known as thioether rings). There are 2 types of lantibiotic:

Type A (which include nisin, subtilin, epidermin, gallidermin and Pep5) are strongly cationic and bactericidal - nisin, subtilin and Pep5 inhibit the growth of Gram-positive bacteria, probably by voltage-dependent pore formation in the cytoplasmic membrane, resulting in cellular efflux of electrolytes, amino acids and ATP;

Type B lantibiotics possess at most one positive charge and are not bactericidal.

This entry represents type A Lantibiotics that are mostly from Bacillales.
Beta/alpha-defensin, C-terminal (Beta/alpha-defensin_C)
Type: Domain

This is a cysteine-rich domain found at the C-terminal end of alpha and beta defensins mainly from mammals that lyse bacteria, fungi and enveloped viruses by forming multimeric membrane-spanning channels.

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. Every mammalian species explored thus far has beta-defensins. In cows, as many as 13 beta-defensins exist in neutrophils. However, in other species, beta-defensins are more often produced by epithelial cells lining various organs (e.g. the epidermis, bronchial tree and genitourinary tract). Theta-defensins are cyclic and have so far only been identified in primate phagocytes.

Neutrophil alpha-defensin has antimicrobial activity against Gram-negative bacteria, and to a lesser extent also against Gram-positive bacteria and fungi. It also protects blood cells against infection with HIV-1 (in vitro) and inhibits corticotropin (ACTH)-stimulated corticosterone production .
Alpha-defensin, C-terminal (Alpha-defensin_C)
Type: Domain

This entry represents the C-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.
Phosphoribulokinase (PRK)
Type: Family

Phosphoribulokinase (PRK)

catalyses the ATP-dependent phosphorylation of ribulose-5-phosphate to ribulose-1,5-phosphate, a key step in the pentose phosphate pathway where carbon dioxide is assimilated by autotrophic organisms . In general, plant enzymes are light-activated by the thioredoxin/ferredoxin system, while those from photosynthetic bacteria are regulated by a system that has an absolute requirement for NADH. Thioredoxin/ferredoxin regulation is mediated by the reversible oxidation/reduction of sulphydryl and disulphide groups. In the spinach enzyme (

) the participating residues are Cys-16 and Cys-55. Sequence analysis shows the first of these cysteines to be present in the ATP-binding site ; neither is found in the bacterial sequences.
Phosphoribulokinase/uridine kinase (PRK/URK)
Type: Domain

Phosphoribulokinase (PRK)

catalyses the ATP-dependent phosphorylation of ribulose-5-phosphate to ribulose-1,5-phosphate, a key step in the pentose phosphate pathway where carbon dioxide is assimilated by autotrophic organisms . In general, plant enzymes are light-activated by the thioredoxin/ferredoxin system, while those from photosynthetic bacteria are regulated by a system that has an absolute requirement for NADH. Thioredoxin/ferredoxin regulation is mediated by the reversible oxidation/reduction of sulphydryl and disulphide groups.
XPG/Rad2 endonuclease (XPG/Rad2)
Type: Family

Xeroderma pigmentosum (XP) is a human autosomal recessive disease, characterised by a high incidence of sunlight-induced skin cancer. People's skin cells with this condition are hypersensitive to ultraviolet light, due to defects in the incision step of DNA excision repair. There are a minimum of seven genetic complementation groups involved in this pathway: XP-A to XP-G. XP-G is one of the most rare and phenotypically heterogeneous of XP, showing anything from slight to extreme dysfunction in DNA excision repair . XP-G can be corrected by a 133 Kd nuclear protein, XPGC . XPGC is an acidic protein that confers normal UV resistance in expressing cells . It is a magnesium-dependent, single-strand DNA endonuclease that makes structure-specific endonucleolytic incisions in a DNA substrate containing a duplex region and single-stranded arms . XPGC cleaves one strand of the duplex at the border with the single-stranded region .

XPG (ERCC-5) belongs to a family of proteins that includes RAD2 from Saccharomyces cerevisiae (Baker's yeast) and rad13 from Schizosaccharomyces pombe (Fission yeast), which are single-stranded DNA endonucleases ; mouse and human FEN-1, a structure-specific endonuclease; RAD2 from fission yeast and RAD27 from budding yeast; fission yeast exo1, a 5'-3' double-stranded DNA exonuclease that may act in a pathway that corrects mismatched base pairs; yeast DHS1, and yeast DIN7. Sequence alignment of this family of proteins reveals that similarities are largely confined to two regions. The first is located at the N-terminal extremity (N-region) and corresponds to the first 95 to 105 amino acids. The second region is internal (I-region) and found towards the C terminus; it spans about 140 residues and contains a highly conserved core of 27 amino acids that includes a conserved pentapeptide (E-A-[DE]-A-[QS]). It is possible that the conserved acidic residues are involved in the catalytic mechanism of DNA excision repair in XPG. The amino acids linking the N-and I-regions are not conserved.

Proteins in this family also includes yeast Mkt1, which is a post-transcriptional regulator. It contains two domains, XPG-N and XPG-I, which are conserved among a family of nucleases. However, it contains only two of the seven Asp residues involved in Mg2 binding suggesting that it has no nuclease activity .
XPG, N-terminal (XPG_DNA_repair_N)
Type: Domain

Xeroderma pigmentosum (XP) is a human autosomal recessive disease, characterised by a high incidence of sunlight-induced skin cancer. People's skin cells with this condition are hypersensitive to ultraviolet light, due to defects in the incision step of DNA excision repair. There are a minimum of seven genetic complementation groups involved in this pathway: XP-A to XP-G. XP-G is one of the most rare and phenotypically heterogeneous of XP, showing anything from slight to extreme dysfunction in DNA excision repair . XP-G can be corrected by a 133 Kd nuclear protein, XPGC . XPGC is an acidic protein that confers normal UV resistance in expressing cells . It is a magnesium-dependent, single-strand DNA endonuclease that makes structure-specific endonucleolytic incisions in a DNA substrate containing a duplex region and single-stranded arms . XPGC cleaves one strand of the duplex at the border with the single-stranded region .

XPG (ERCC-5) belongs to a family of proteins that includes RAD2 from Saccharomyces cerevisiae (Baker's yeast) and rad13 from Schizosaccharomyces pombe (Fission yeast), which are single-stranded DNA endonucleases ; mouse and human FEN-1, a structure-specific endonuclease; RAD2 from fission yeast and RAD27 from budding yeast; fission yeast exo1, a 5'-3' double-stranded DNA exonuclease that may act in a pathway that corrects mismatched base pairs; yeast DHS1, and yeast DIN7. Sequence alignment of this family of proteins reveals that similarities are largely confined to two regions. The first is located at the N-terminal extremity (N-region) and corresponds to the first 95 to 105 amino acids. The second region is internal (I-region) and found towards the C terminus; it spans about 140 residues and contains a highly conserved core of 27 amino acids that includes a conserved pentapeptide (E-A-[DE]-A-[QS]). It is possible that the conserved acidic residues are involved in the catalytic mechanism of DNA excision repair in XPG. The amino acids linking the N-and I-regions are not conserved.

This entry represents the N-terminal of XPG.
XPG-I domain (XPG-I_dom)
Type: Domain

This entry represents a domain found on Xeroderma Pigmentosum Complementation Group G (XPG) protein . XPG is a DNA endonuclease involved in DNA excision repair . The internal XPG (XPG-I) domain contains many cysteine and glutamate amino acid residues that are frequently found in various enzyme active sites of DNA nucleases. The I domain, together with the N-terminal, forms the catalytic domain that contains the active site .
Acyl-CoA dehydrogenase, conserved site (Acyl-CoA_DH_CS)
Type: Conserved_site

Mammalian Co-A dehydrogenases (

) are enzymes that catalyse the first step in each cycle of beta-oxidation in mitochondion. Acyl-CoA dehydrogenases catalyze the alpha,beta-dehydrogenation of acyl-CoA thioesters to the corresponding trans 2,3-enoyl CoA-products with concommitant reduction of enzyme-bound FAD. Reoxidation of the flavin involves transfer of electrons to ETF (electron transfering flavoprotein) . These enzymes are homodimers containing one molecule of FAD.
Acyl-CoA oxidase/dehydrogenase, middle domain (Acyl-CoA_Oxase/DH_mid-dom)
Type: Domain

Acyl-CoA dehydrogenases (

) are a family of flavoproteins that catalyse the alpha,beta-dehydrogenation of acyl-CoA thioesters to the corresponding trans 2,3-enoyl CoA-products with the concomitant reduction of enzyme-bound FAD. Different family members share a high sequence identity, catalytic mechanisms, and structural properties, but differ in the position of their catalytic bases and in their substrate binding specificity. Butyryl-CoA dehydrogenase prefers short chain substrates, medium chain-and long-chain acyl-CoA dehydrogenases prefer medium and long chain substrates, respectively, and Isovaleryl-CoA dehydrogenase prefers branched-chain substrates.

The monomeric enzyme is folded into three domains of approximately equal size, where the N-terminal domain is all-α, the middle domain is an open (5,8) barrel, and the C-terminal domain is a four-helical bundle. The constituent families differ in the numbers of C-terminal domains. This entry represents the middle β-barrel domain found in medium chain acyl-CoA dehydrogenases, as well as in the related peroxisomal acyl-CoA oxidase-II enzymes. Acyl-CoA oxidase (ACO;

) catalyses the first and rate-determining step of the peroxisomal beta-oxidation of fatty acids .
Oxygen oxidoreductase covalent FAD-binding site (Oxy_OxRdtase_FAD_BS)
Type: Binding_site

This entry represents the conserved region around the histidine that binds the FAD group, which is conserved in these enzymes.

Some oxygen-dependent oxidoreductases are flavoproteins that contain a covalently bound FAD group which is attached to a histidine via an 8-alpha- (N3-histidyl)-riboflavin linkage. These proteins include:

(R)-6-hydroxynicotine oxidase (EC 1.5.3.6) (6-HDNO) , a bacterial enzyme that catalyzes the oxygen-dependent degradation of 6-hydroxynicotine into 6-hydroxypyrid-N-methylosmine.

Plant reticuline oxidase (EC 1.21.3.3) (berberine-bridge-forming enzyme), an enzyme that catalyzes the oxidation of (S)-reticuline into (S)- scoulerine in the pathway leading to benzophenanthridine alkaloids.

L-gulonolactone oxidase (EC 1.1.3.8) (l-gulono-gamma-lactone oxidase) , a mammalian enzyme which catalyzes the oxidation of L-gulono-1,4-lactone to L-xylo-hexulonolactone which spontaneously isomerizes to L-ascorbate.

D-arabinono-1,4-lactone oxidase (EC 1.1.3.24) (L-galactonolactone oxidase), a yeast enzyme involved in the biosynthesis of D-erythroascorbic acid .

Mitomycin radical oxidase , a bacterial protein involved in mitomycin resistance and that probably oxidizes the reduced form of mitomycins.

Cytokinin oxidase (EC 1.4.3.18), a plant enzyme.

Rhodococcus fascians fasciation locus protein fas5.
FAD linked oxidase, N-terminal (Oxid_FAD_bind_N)
Type: Domain

Various enzymes use FAD as a co-factor, most of these enzymes are oxygen-dependent oxidoreductases, containing a covalently bound FAD group which is attached to a histidine via an 8-alpha-(N3-histidyl)-riboflavin linkage. One of the enzymes Vanillyl-alcohol oxidase (VAO,

) has a solved structure, the alignment includes the FAD binding site, called the PP-loop, between residues 99-110 . The FAD molecule is covalently bound in the known structure, however the residue that links to the FAD is not in the alignment. VAO catalyses the oxidation of a wide variety of substrates, ranging from aromatic amines to 4-alkylphenols. Other enzymes included in this family are MurB family members UDP-N-acetylenolpyruvoylglucosamine reductases involved in the biosynthesis of peptidoglycan , D-lactate dehydrogenases among many others oxidoreductases.