SII-SWORD/CoKE huggingface dataset:
Quinolinate synthase A, type 2 (Quinolinate_synth_type2)
Type: Family

This entry represents a group of bacterial type 2 quinolinate synthetases (NadA).

Quinolinate synthetase catalyses the second step of the
de novo
biosynthetic pathway of pyridine nucleotide formation. In particular, quinolinate synthetase is involved in the condensation of dihydroxyacetone phosphate and iminoaspartate to form quinolinic acid . This synthesis requires two enzymes, an FAD-containing "B protein" and an "A protein".
DNA protection during starvation protein, gammaproteobacteria (Dps_gammaproteobac)
Type: Family

This group belongs to the ferritin domain superfamily and has the ferritin-like structural fold. Ferritins constitute a broad superfamily of iron storage proteins, widespread in all domains of life . Ferritins and bacterioferritins have essentially the same architecture, assembling in a 24mer cluster to form a hollow, roughly spherical, construction. This consists of a mineral core of hydrated ferric oxide and a multi-subunit protein shell, which encloses the former and assures its solubility in an aqueous environment. Due to the absence of the C-terminal fifth helix of 24mer ferritins, members of the Dps group assemble only to dodecameric protein shells .

Members of this entry were originally discovered as stress proteins, which protect DNA against oxidative stress during nutrient starvation , hence the name Dps (DNA protection during starvation protein). Several members of the group, such as Dps from Escherichia coli, exhibit a DNA-binding activity that is at least partially linked with iron complexation . DNA binding by these proteins was shown to suffice for protection against oxidative DNA damage and might be mediated by magnesium ions, which bridge the protein surfaces with the polyanionic DNA . Dps also contributes to defense against copper stress in growing cells of E. coli .
CCA-adding enzyme, firmicutes (CCA-adding_enz_firmicutes)
Type: Family

This family consists of CCA tRNA adenylyltransferases from the firmicutes . CCA tRNA nucleotidyltransferase, also known as CCA-adding enzyme, are responsible for the synthesis and repair of the 3' terminal CCA sequence of tRNA molecules. They are encoded by essential genes in almost all organisms and add the three ribonucleotides C, C, and A to the 3' end of tRNAs in sequential order.
Chaperone TorD (Chaperone_TorD)
Type: Family

The TorD protein, after which this family is named, is involved in the maturation of the the trimethylamine N-oxide reductase TorA in Escherichia coli . TorA is a molybdenum-containing enzyme which requires the the insertion of a bis(molybdopterin guanine dinucleotide) molybdenum (bis(MGD)Mo) cofactor in its catalytic site to be active and translocated to the periplasm. TorD acts as a chaperone, binding to apoTorA and promoting efficient incorporation of the cofactor into the protein.
DnaA initiator-associating protein (DiaA)
Type: Family

This entry represents DnaA initiator-associating proteins which are required for the timely initiation of chromosomal replication .
Transcriptional regulator, SlyA (Tscrpt_reg_SlyA)
Type: Family

This entry represents transcriptional regulators SlyA.

In Escherichia coli, SlyA activates expression of genes such as molecular chaperones (groL, groS, dnaK, grpE, and cbpA), proteins involved in acid resistance (hdeA, hdeB, and gadA), the starvation lipoprotein slp, virulence protein hlyE/clyA. Represses expression of genes involved in the histidine biosynthetic pathway such as hisA, hisB, hisD, hisF and hisG. Required for the activation of virulence genes .
Acetyltransferase, YpeA (Acetyltransferase_YpeA)
Type: Family

This entry represents acetyltransferases, YpeA.
DNA polymerase, error-prone (DnaE2)
Type: Family

The error-prone DNA polymerase is involved in damage-induced mutagenesis and translesion synthesis (TLS). It is not the major replicative DNA polymerase.
Hydroxymethylglutaryl-CoA reductase, class I/II, catalytic domain superfamily (HMG_CoA_Rdtase_cat_sf)
Type: Homologous_superfamily

There are two distinct classes of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase enzymes: class I consists of eukaryotic and most archaeal enzymes (

), while class II consists of prokaryotic enzymes (

) .

Class I HMG-CoA reductases catalyse the NADP-dependent synthesis of mevalonate from 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). In vertebrates, membrane-bound HMG-CoA reductase is the rate-limiting enzyme in the biosynthesis of cholesterol and other isoprenoids. In plants, mevalonate is the precursor of all isoprenoid compounds . The reduction of HMG-CoA to mevalonate is regulated by feedback inhibition by sterols and non-sterol metabolites derived from mevalonate, including cholesterol. In archaea, HMG-CoA reductase is a cytoplasmic enzyme involved in the biosynthesis of the isoprenoids side chains of lipids . Class I HMG-CoA reductases consist of an N-terminal membrane domain (lacking in archaeal enzymes), and a C-terminal catalytic region. The catalytic region can be subdivided into three domains: an N-domain (N-terminal), a large L-domain, and a small S-domain (inserted within the L-domain). The L-domain binds the substrate, while the S-domain binds NADP.

Class II HMG-CoA reductases catalyse the reverse reaction of class I enzymes, namely the NAD-dependent synthesis of HMG-CoA from mevalonate and CoA . Some bacteria, such as Pseudomonas mevalonii, can use mevalonate as the sole carbon source. Class II enzymes lack a membrane domain. Their catalytic region is structurally related to that of class I enzymes, but it consists of only two domains: a large L-domain and a small S-domain (inserted within the L-domain). As with class I enzymes, the L-domain binds substrate, but the S-domain binds NAD (instead of NADP in class I).

This superfamily represents the catalytic domain found in both class I and II HMG-CoA reductases. The catalytic domain from both classes share a common overall structural fold, despite low sequence identities of 14-20%.
Hydroxymethylglutaryl-CoA reductase, class I/II, conserved site (HMG_CoA_Rdtase_CS)
Type: Conserved_site

There are two distinct classes of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase enzymes: class I consists of eukaryotic and most archaeal enzymes (

), while class II consists of prokaryotic enzymes (

) .

Class I HMG-CoA reductases catalyse the NADP-dependent synthesis of mevalonate from 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). In vertebrates, membrane-bound HMG-CoA reductase is the rate-limiting enzyme in the biosynthesis of cholesterol and other isoprenoids. In plants, mevalonate is the precursor of all isoprenoid compounds . The reduction of HMG-CoA to mevalonate is regulated by feedback inhibition by sterols and non-sterol metabolites derived from mevalonate, including cholesterol. In archaea, HMG-CoA reductase is a cytoplasmic enzyme involved in the biosynthesis of the isoprenoids side chains of lipids . Class I HMG-CoA reductases consist of an N-terminal membrane domain (lacking in archaeal enzymes), and a C-terminal catalytic region. The catalytic region can be subdivided into three domains: an N-domain (N-terminal), a large L-domain, and a small S-domain (inserted within the L-domain). The L-domain binds the substrate, while the S-domain binds NADP.

Class II HMG-CoA reductases catalyse the reverse reaction of class I enzymes, namely the NAD-dependent synthesis of HMG-CoA from mevalonate and CoA . Some bacteria, such as Pseudomonas mevalonii, can use mevalonate as the sole carbon source. Class II enzymes lack a membrane domain. Their catalytic region is structurally related to that of class I enzymes, but it consists of only two domains: a large L-domain and a small S-domain (inserted within the L-domain). As with class I enzymes, the L-domain binds substrate, but the S-domain binds NAD (instead of NADP in class I).

This entry represents three conserved sites found in HMG-CoA reductases. The first is located in the centre of the catalytic domain, the second is a glycine-rich region located in the C-terminal section of the same catalytic domain and the third is also located in the C-terminal section and contains an histidine residue that appears to be implicated in the catalytic mechanism as a general base .
Sedoheptulose-1,7-bisphosphatase (SBPase)
Type: Family

This entry represents sedoheptulose-1,7-bisphosphatase. Sedoheptulose- 1,7-bisphosphate is involved in carbohydrate biosynthesis, catalysing the production of sedoheptulose 7-phosphate and phosphate from sedoheptulose- 1,7-bisphosphate and water. The enzyme shares a high degree of similarity with fructose-1,6-bisphosphatases, but it does not contain the regulatory motif present in the latter . This entry also includes a group of fructose-1,6-bisphosphatases with a higher degree of similarity to sedoheptulose-1,7-bisphosphatase than to other fructose-1,6-bisphosphatases.
D-amino acid dehydrogenase DadA (DadA)
Type: Family

DadA is a dehydrogenase catalysing the deamination of D-amino acids yielding corresponding 2-oxo acids and hydrogen . D-Amino acids control growth phase-dependent cell wall remodelling and rigger biofilm disassembly .
Cell division protein FtsB (Cell_div_FtsB)
Type: Family

The proteins in this entry are represented by the Escherichia coli (strain K12) protein FtsB. FtsB is one of the three membrane proteins required for cell division in E. coli: FtsQ, FtsL and FtsB, all of these localize to the cell septum. FtsL and FtsB contain a leucine zipper-like sequence and are dependent on each other for their localization to the septum and each of them is dependent on FtsQ. FtsQ is found at the cell division site in the absence of FtsL and FtsB and requires FtsK for its localization .
Homeo-prospero domain (Homeo_prospero_dom)
Type: Domain

This entry represents the homeo-prospero domain. This domain consists of a homeodomain-homology N-terminal region and the prospero-specific C-terminal region. The structure of these two regions consists of a single structural unit (a homeo-prospero domain), in which the prospero domain region is in position to contribute to DNA binding and also to mask a defined nuclear export signal that is within the putative homeodomain region. It is proposed that the homeo-prospero domain coordinately regulates prospero nuclear localisation and DNA binding specificity .

Prospero is a large Drosophila transcription factor protein that is expressed in all neural lineages of Drosophila embryos. It is needed for correct expression of several neural proteins and in determining the cell fates of neural stem cells. Homologues of prospero are found in a wide range of animals including humans with the highest level of similarity being found in the C-terminal 160 amino acids. This region was identified as containing an atypical homeobox domain followed by a prospero domain. However, the structure shows that these two regions form a single stable structural domain as defined here . This homeo-prospero domain binds to DNA.
Glycerol-3-phosphate O-acyltransferase, alpha-helical bundle, N-terminal (G3P_O-acylTrfase_N)
Type: Domain

Stromal glycerol-3-phosphate acyltransferases (GPAT) are responsible for the selective incorporation of saturated and unsaturated fatty-acyl chains into chloroplast membranes, which is an important determinant of a plant's ability to tolerate chilling temperatures . This entry represents the N-terminal four α helical bundle found in these proteins.
Proteinase inhibitor I11, ecotin, gammaproteobacteria (Prot_inh_ecotin_gammaproteobac)
Type: Family

This entry represents bacterial proteinase inhibitors that belong to MEROPS inhibitor family I11, clan IN. Ecotins are dimeric periplasmic proteins from Escherichia coli and related Gram-negative bacteria that have been shown to be potent inhibitors of many trypsin-fold serine proteases of widely varying substrate specificity, which belong to MEROPS peptidase family S1 (

) . Phylogenetic analysis suggested that ecotin has an exogenous target, possibly neutrophil elastase. Ecotin from E. coli, Yersinia pestis, and Pseudomonas aeruginosa, all species that encounter the mammalian immune system inhibit neutrophil elastase strongly while ecotin from the plant pathogen Pantoea citrea inhibits neutrophil elastase 1000-fold less than the others .

Ecotin inhibits chymotrypsin, trypsin, elastases, factor X, kallikrein as well as a variety of other proteases. The inhibition mechanism involves binding at two different protease contact sites: the primary and secondary binding sites. Primary site loops of ecotin bind to the active site of target proteases in a substrate-like manner with the P1 residue in ecotin mimicking the interactions of a canonical P1 substrate residue .
UDP-N-acetyl-D-mannosaminuronic acid transferase (UDP-ManNAcA_Trfase_WecG)
Type: Family

This entry represents UDP-N-acetyl-D-mannosaminuronic acid transferases that belong to the glycosyltransferase 26 family. It has been proposed that these proteins catalyze the synthesis of Und-PP-GlcNAc-ManNAcA (Lipid II), the second lipid-linked intermediate involved in enterobacterial common antigen synthesis.
Phosphoglycerate mutase, GpmB, probable (Phosphoglycerate_mutase_GpmB)
Type: Family

This entry represents probable phosphoglycerate mutases (PGAM) that belong to the GpmB subfamily.
Flagellar motor switch protein FliG, C-terminal (Flg_Motor_Flig_C)
Type: Domain

The flagellar motor switch in Escherichia coli and Salmonella typhimurium regulates the direction of flagellar rotation and hence controls swimming behaviour . The switch is a complex apparatus that responds to signals transduced by the chemotaxis sensory signalling system during chemotactic behaviour . CheY, the chemotaxis response regulator, is believed to act directly on the switch to induce tumbles in the swimming pattern, but no physical interactions of CheY and switch proteins have yet been demonstrated.

This entry represents the C-terminal domain of FliG, the structure of which is known. This domain functions specifically in motor rotation .
3'5'-cyclic nucleotide phosphodiesterase (PDEase)
Type: Family

The cyclic nucleotide phosphodiesterases (PDE) comprise a group of enzymes that degrade the phosphodiester bond in the second messenger molecules cAMP and cGMP. They are divided into 11 families. They regulate the localisation, duration and amplitude of cyclic nucleotide signalling within subcellular domains. PDEs are therefore important for signal transduction.

PDE enzymes are often targets for pharmacological inhibition due to their unique tissue distribution, structural properties, and functional properties. Inhibitors include: Roflumilast for chronic obstructive pulmonary disease and asthma , Sildenafil for erectile dysfunction and Cilostazol for peripheral arterial occlusive disease , amongst others.

Retinal 3',5'-cGMP phosphodiesterase is located in photoreceptor outer segments: it is light activated, playing a pivotal role in signal transduction . In rod cells, PDE is oligomeric, comprising an alpha-, a beta-and 2 gamma-subunits, while in cones, PDE is a homodimer of alpha chains, which are associated with several smaller subunits. Both rod and cone PDEs catalyse the hydrolysis of cAMP or cGMP to the corresponding nucleoside 5' monophosphates, both enzymes also binding cGMP with high affinity. The cGMP-binding sites are located in the N-terminal half of the protein sequence, while the catalytic core resides in the C-terminal portion.
YozE SAM-like domain (YozE_SAM-like)
Type: Domain

YozE-like is a family of Firmicute proteins that carries a four-helix motif similar to sterile alpha motif (SAM) domains. The family is suggested to fall into two subfamilies, possibly with differing functions based on the different surface charges on the three structural representatives, YozE, MW0776 and MW1311. This function is not yet known, although it is likely to involve binding to DNA .
UPF0702, alpha/beta domain superfamily (UPF0702_alpha/beta_dom_sf)
Type: Homologous_superfamily

This superfamily represents a 2 layer α/β sandwich domain that is found in an uncharacterised protein family. This domain is often tandemly repeated.
Metalloprotease catalytic domain superfamily, predicted (MetalPrtase_cat_dom_sf_prd)
Type: Homologous_superfamily

This superfamily represents a domain found in a number of predicted metalloproteases. 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 metalloproteases such as collagenases and gelatinases. However, experimental tests for collagenase and gelatinase-type function show no detectable activity under standard assay conditions .
ScpA-like, C-terminal (ScpA-like_C)
Type: Homologous_superfamily

This superfamily represents a conserved C-terminal region found in bacterial segregation and condensation protein A (ScpA) as well as in eukaryotic cohesins of the Rad21 and Scc1 families. ScpA participates in chromosomal partition during cell division. It may act via the formation of a condensin-like complex containing Smc and ScpB that pull DNA away from mid-cell into both cell halves.
Adenine-specific methyltransferase, domain 2 (Ade_MeTrfase_dom_2)
Type: Homologous_superfamily

This superfamily represents the α-helical domain (also refered as domain 2) found in the adenine-specific N(4)/N(6)-methyltransferase family. It is around 100 amino acids in length.
Phosphoglucose isomerase, C-terminal (G6P_Isomerase_C)
Type: Homologous_superfamily

Phosphoglucose isomerase (

) (PGI) is a dimeric enzyme that catalyses the reversible isomerization of glucose-6-phosphate and fructose-6-phosphate. PGI is involved in different pathways: in most higher organisms it is involved in glycolysis; in mammals it is involved in gluconeogenesis; in plants in carbohydrate biosynthesis; in some bacteria it provides a gateway for fructose into the Entner-Doudouroff pathway. The multifunctional protein, PGI, is also known as neuroleukin (a neurotrophic factor that mediates the differentiation of neurons), autocrine motility factor (a tumour-secreted cytokine that regulates cell motility), differentiation and maturation mediator and myofibril-bound serine proteinase inhibitor, and has different roles inside and outside the cell. In the cytoplasm, it catalyses the second step in glycolysis, while outside the cell it serves as a nerve growth factor and cytokine .

This superfamily represents the C-terminal domain of phosphoglucose isomerase. It is α helical and not found in archaeal proteins.
L-serine kinase SerK/SbnI, C-terminal (SerK/SbnI_C)
Type: Homologous_superfamily

This superfamily represents a structural α-β domain found in the C-terminal region of free serine kinase (SerK) from Thermococcus kodakarensis and SbnI from Staphylococcus aureus . SerK converts ADP and l-serine (Ser) into AMP and O-phospho-l-serine (Sep), which is a precursor of l-cysteine .
Glycoside hydrolase, family 46, N-terminal (Glyco_hydro_46_N)
Type: Homologous_superfamily

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 46

comprises enzymes with only one known activity; chitosanase (

).

Chitosanase enzymes catalyse the endohydrolysis of beta-1,4-linkages between N-acetyl-D-glucosamine and D-glucosamine residues in a partly acetylated chitosan. Chitosan is a biopolymer of beta (1,4)-linked -D-glucosamine (GlcN) residues produced by partial or full deacetylation of chitin. Chitosanases play a role in defense against pathogens such as fungi and are found in microorganisms, fungi, viruses, and plants. Microbial chitosanases whose members are the most prevalent can be divided into 3 subclasses based on the specificity of the cleavage positions for partial acetylated chitosan. Subclass I chitosanases such as N174 can split GlcN-GlcN and GlcNAc-GlcN linkages, whereas subclass II chitosanases such as Bacillus sp. no. 7-M can cleave only GlcN-GlcN linkages. Subclass III chitosanases such as MH-K1 chitosanase are the most versatile and can split both GlcN-GlcN and GlcN-GlcNAc linkages .

This entry represents the predominantly α-helical N-terminal domain found in chitosanases .
D-aminoacylase, insert domain superfamily (D-aminoacylase_insert_dom_sf)
Type: Homologous_superfamily

This superfamily represents the insert found in the catalytic domain. This insert, composed of two α-helices and four β-strands, goes across the active site and is involved in substrate-mediated conformational change.

D-aminoacylase hydrolyses a wide variety of N-acyl derivatives of neutral D-amino acids, in a zinc-dependent manner. The enzyme is composed of a small β-barrel domain and a larger catalytic α/β-barrel that contains a short α/β insert. The overall structure shares significant similarity to the α/β-barrel amidohydrolase superfamily, in which the β-strands in both barrels superimpose well .
AF1862-like domain superfamily (AF1862-like_dom_sf)
Type: Homologous_superfamily

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.

This superfamily represents the structural domain found in a family of Cas proteins as represented by TM1791.1 from Thermotoga maritima and AF1862 from Archaeoglobus fulgidus. This family of Cas proteins are found in both archaeal and bacterial species.
ITPase-like domain superfamily (ITPase-like_dom_sf)
Type: Homologous_superfamily

This superfamily represents a structural domain found in a family of proteins with unknown function.
YkvR-like superfamily (YkvR-like_sf)
Type: Homologous_superfamily

This domain superfamily is found in proteins with unknown function that appears to be restricted to Bacillaceae. Some members in this family of proteins are annotated as YkvR however this cannot be confirmed.
Atu2299-like domain superfamily (Atu2299-like_dom_sf)
Type: Homologous_superfamily

This superfamily represents a domain found in a family of protein of approx. 100 residues. The proteins contain up to five α helices and up to seven β strands and are probably monomeric. Their function is unknown.
Domain of unknown function, DUF3216 (DUF3216)
Type: Domain

This domain is found in a family of proteins with unknown function and appears to be restricted to the Thermococcaceae.
PH1570-like domain (PH1570-like_domain)
Type: Domain

This domain is found in a family of proteins that include a hypothetical protein from Pyrococcus horikoshii, which has no known function. It contains six α helices and eight β strands and is thought to be monomeric.
Titin-like domain superfamily (Titin-like_dom_sf)
Type: Homologous_superfamily

The domain found in this superfamily is associated with telethonin, which is found at the Z-disc of sarcomeres. It is the phosphorylation target of the kinase domain of titin, and is thought to play a role in muscle development . Deletion of the C terminus of titin, including the kinase domain, has been found to impair myofibrillogenesis . Mutations of telethonin cause limb-girdle muscular dystrophy type 2G .

Telethonin is a 167-residue protein which complexes with the large muscle protein, titin. The very N terminus of titin, composed of two immunoglobulin-like (Ig) domains, referred to as Z1 and Z2, interacts with the N-terminal region (residues 1-53) of telethonin, mediating the antiparallel assembly of two Z1Z2 domains. The C terminus of telethonin appears to induce dimerisation of this 2:1 titin/telethonin structure which thus forms a complex necessary for myofibril assembly and maintenance of the intact Z-disk of skeletal and cardiac muscles .

This entry represents the N-terminal domain.