SII-SWORD/CoKE huggingface dataset:
DNA gyrase, subunit B (GyrB)
Type: Family

Topoisomerase II (called gyrase in bacteria) primarily introduces negative supercoils into DNA. In bacteria, topoisomerase II consists of two polypeptide subunits, gyrA and gyrB, which form a heterotetramer: (BA)2. In most eukaryotes, topoisomerase II consists of a single polypeptide, where the N-and C-terminal regions correspond to gyrB and gyrA, respectively.

This entry represents the B subunit (gyrB) as found predominantly in bacteria, but does not include the topoisomerase II enzymes composed of a single polypeptide, as are found in most eukaryotes. GyrB has two functional domains: an N-terminal ATPase and a C-terminal responsible for subunit interactions, the latter differing between subunit B and single polypeptide topoisomerase II .

DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single-or double-strand breaks, crossing the strands through one another, then resealing the breaks . These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis . DNA topoisomerases are divided into two classes: type I enzymes (

; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (

; topoisomerases II, IV and VI) break double-strand DNA .

Type II topoisomerases are ATP-dependent enzymes, and can be subdivided according to their structure and reaction mechanisms: type IIA (topoisomerase II or gyrase, and topoisomerase IV) and type IIB (topoisomerase VI). These enzymes are responsible for relaxing supercoiled DNA as well as for introducing both negative and positive supercoils .
Initiation factor 2B alpha/beta/delta (Initiation_fac_2B_a/b/d)
Type: Family

This family describes part of the eukaryotic translation initiation factor 2B superfamily. It includes eukaryotic translation initiation factor 2B (eIF-2B) subunits 1 and 2 (alpha and beta) and related proteins. Members of this branch of the family are predominantly uncharacterised with respect to function and are found in the archaea, bacteria, and eukarya.

Recently, one of these proteins from Bacillus subtilis has been functionally characterised as a 5-methylthioribose-1-phosphate isomerase (MTNA,

, ). This enzyme participates in the methionine salvage pathway catalysing the isomerisation of 5-methylthioribose-1-phosphate to 5-methylthio ribulose-1-phosphate . The methionine salvage pathway leads to the synthesis of methionine from methylthioadenosine, the end product of the spermidine and spermine anabolism in many species.
Telomeric single stranded DNA binding POT1/Cdc13 (Telomer_end-bd_POT1/Cdc13)
Type: Domain

This domain binds single stranded telomeric DNA and adopts an OB fold . It includes the proteins POT1 and Cdc13 which have been shown to regulate telomere length, replication and capping . POT1 is one component of the shelterin complex that protects telomere-ends from attack by DNA-repair mechanisms .
Ubiquinone biosynthesis protein Coq7 (Ubq_synth_Coq7)
Type: Family

Coq7 (also known as Clk-1 and CAT5) is a di-iron carboxylate protein occurring in both prokaryotes and eukaryotes that is essential for ubiquinone biosynthesis . It has been implicated in the ageing process as mutations in the Caenorhabditis elegans gene lead to increased lifespan . Coq7 is a membrane-bound protein that functions as a monooxygenase to hydroxylate demethoxyubiquinone (DMQ or 2-methoxy-5-methyl-6-polyprenyl-1,4-benzoquinone) in the penultimate step of ubiquinone biosynthesis . Biochemical studies indicate that NADH can serve directly as a reductant for catalytic activation of dioxygen and substrate oxidation by the enzyme, with no requirement for an additional reductase protein component . This direct reaction with NADH is so far unique amongst members of the di-iron carboxylate protein family.
Pyridoxamine 5'-phosphate oxidase, N-terminal (Pyridox_Oxase_N)
Type: Domain

Pyridoxamine 5'-phosphate oxidase (PNPOx;

) is a FMN flavoprotein that catalyses the oxidation of pyridoxamine-5-P (PMP) and pyridoxine-5-P (PNP) to pyridoxal-5-P (PLP). This reaction serves as the terminal step in the de novo biosynthesis of PLP in Escherichia coli and as a part of the salvage pathway of this coenzyme in both E. coli and mammalian cells . The binding sites for FMN and for substrate have been highly conserved throughout evolution. In some species, coenzyme F420 may perform the cofactor role instead of FMN .

This entry represents the N-terminal segment which is involved in FMN binding when they form the dimer . In human PNPO, it has been shown that this region contains some of the residues that constitute the PLP allosteric site which regulates its activity . The C-terminal region of these proteins is involved in dimerisation (

). This entry also includes Dihydrophenazinedicarboxylate synthase (PhzG) which catalyses several oxidations in the terminal steps of core phenazine biosynthesis .
Cytochrome b561, bacterial/Ni-hydrogenase (Cyt_b561_bac/Ni-Hgenase)
Type: Domain

Cytochrome b561 is an integral membrane and electron transport protein, that binds two haem groups non-covalently. This domain is also found in a number of nickel-dependent hydrogenase subunits which are also B-type cytochromes that interact with quinones and anchor the hydrogenase to the membrane. This domain is found in prokaryotes. Members of the 'eukaryotic cytochrome b561' family can be found in

.
ATPase domain (ATPase_dom)
Type: Domain

This domain contains a conserved P-loop motif that is involved in binding ATP .
Chitinase II/V-like, catalytic domain (Chitinase_II/V-like_cat)
Type: Domain

This entry represents the catalytic domain of a group of proteins from the glycoside hydrolase, family 18

. Members of this family belong to the chitinase class II/V and IDGF (Imaginal disk growth factor) groups, which includes chitinase, chitodextrinase and the killer toxin of Kluyveromyces lactis (Yeast) (Candida sphaerica). The chitinases hydrolyse chitin oligosaccharides. However, glycoside hydrolase family 18 also includes chitinase-like proteins, which bind but do not cleave chitin .

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.
Green fluorescent protein-related (GFP-related)
Type: Family

The green fluorescent protein (GFP) is found in the jellyfish (Aequorea victoria), and functions as an energy-transfer acceptor. It fluoresces
in vivo
upon receiving energy from the
Ca
2+
-activated photoprotein aequorin. The protein absorbs light maximally at 395 nm and exhibits a smaller absorbance peak at 470 nm. The fluorescence emission spectrum peaks at 509 nm with a shoulder at 540 nm. The protein is produced in the photocytes and contains a chromophore, which is composed of modified amino acid residues. The chromophore is formed upon cyclisation of the residues ser-dehydrotyr-gly. There are several other members of the GFP family, which are able to fluoresce different colours, several of which are non-fluorescent . These proteins are all essentially encoded by single genes, since both the substrate and the catalytic enzyme for pigment biosynthesis are provided within a single polypeptide chain .
Protein of unknown function UCP004961 (UCP004961)
Type: Family

This family of proteins are related to a large superfamily of metalloenzymes . It shares protein sequence similarity with TatD, which is an DNase that is also part of the twin-arginine translocation (Tat) system that transports large folded proteins containing a characteristic twin-arginine motif in their signal peptide across membranes in Escherichia coli .
Transcription elongation factor Spt5, archaeal (Spt5_arc)
Type: Family

Transcription elongation factor Spt5 is composed of a NusG N-terminal (NGN) domain and a KOW domain, similar to bacterial NusG . It forms heterodimer with Spt4 and stimulates transcription elongation . Its NGN domain closes the RNAP active centre cleft to lock nucleic acids and render the elongation complex stable and processive . Its KOW domain may interact with RNA and/or other factors . The structure of Spt4/5 complex has been solved .
Prefoldin alpha subunit, archaea-type (PFD_alpha_archaea)
Type: Family

Prefoldin (PFD) is a chaperone that interacts exclusively with type II chaperonins, hetero-oligomers lacking an obligate co-chaperonin that are found only in eukaryotes (chaperonin-containing T-complex polypeptide-1 (CCT)) and archaea. Eukaryotic PFD is a multi-subunit complex containing six polypeptides in the molecular mass range of 14-23kDa. In archaea, on the other hand, PFD is composed of two types of subunits, two alpha and four beta. The six subunits associate to form two back-to-back up-and-down eight-stranded barrels, from which hang six coiled coils. Each subunit contributes one (beta subunits) or two (alpha subunits) β hairpin turns to the barrels. The coiled coils are formed by the N and C termini of an individual subunit. Overall, this unique arrangement resembles a jellyfish. The eukaryotic PFD hexamer is composed of six different subunits; however, these can be grouped into two alpha-like (PFD3 and -5) and four beta-like (PFD1, -2, -4, and -6) subunits based on amino acid sequence similarity with their archaeal counterparts. Eukaryotic PFD has a six-legged structure similar to that seen in the archaeal homologue .

This entry represents the archaeal alpha subunit and the closely related eukaryotic subunit 5.
Peptidase C14, caspase domain (Pept_C14_caspase)
Type: Domain

This domain can be found in caspases (MEROPS family C12A) and metacaspases (MEROPS family C14B). Metacaspases adopt a caspase fold, with active site loops arranged similarly as other caspases .

Caspases (Cysteine-dependent ASPartyl-specific proteASE) are cysteine peptidases . They are tightly regulated proteins that require zymogen activation to become active, and once active can be regulated by caspase inhibitors. Caspases are mainly involved in mediating cell death (apoptosis) . They have two main roles within the apoptosis cascade: as initiators that trigger the cell death process, and as effectors of the process itself. Caspases can have roles other than in apoptosis, such as caspase-1 (interleukin-1 beta convertase) (

), which is involved in the inflammatory process. The activation of apoptosis can sometimes lead to caspase-1 activation, providing a link between apoptosis and inflammation, such as during the targeting of infected cells. Caspases may also be involved in cell differentiation .

Metacaspases are arginine/lysine-specific, in contrast to caspases, which are aspartate-specific. They are found only in plants , fungi and lower eukaryotes, including the protozoa . While plant metacaspases have been shown to be involved in cell death pathways, in other organisms they have evolved alternative functions .
UDP-N-acetylenolpyruvoylglucosamine reductase, C-terminal (MurB_C)
Type: Domain

This entry represents a C-terminal conserved region of UDP-N-acetylenolpyruvoylglucosamine reductase

, which is also called UDP-N-acetylmuramate dehydrogenase. The C-terminal domain is involved in substrate binding . It is a part of the pathway for the biosynthesis of the UDP-N-acetylmuramoyl-pentapeptide, which is a precursor of bacterial peptidoglycan.
Type II pantothenate kinase, bacterial (Type_II_PanK_bac)
Type: Family

Pantothenate kinase (PanK or CoaA) catalyses the first step of the universal five step coenzyme A (CoA) biosynthesis pathway. Three distinct types of pantothenate kinase enzymes have been identified: type I PanK enzymes are typified by the E. coli CoaA protein; type II enzymes are primarily found in eukaryotic organisms; whilst type III enzymes have a wider phylogenic distribution and are not feedback inhibited by CoA .

This entry represents PanK type II family members from bacteria, which may have originated from the eukaryotic form by lateral transfer.
2-oxoglutarate dehydrogenase E1 component (2oxoglutarate_DH_E1)
Type: Family

2-oxoglutarate dehydrogenase is a key enzyme in the TCA cycle, converting 2-oxoglutarate, coenzyme A and NAD(+) to succinyl-CoA, NADH and carbon dioxide . This activity of this enzyme is tightly regulated and it is a major determinant of the metabolic flux through the TCA cycle. This enzyme is composed of multiple copies of three different subunits: 2-oxoglutarate dehydrogenase (E1), dihydrolipoamide succinyltransferase (E2) and lipoamide dehydrogenase (E3) which is often shared with similar enzymes such as pyruvate dehydrogenase . The E2 component forms a large multimeric core which binds the peripheral E1 and E3 subunits. The substrate is transferred between the active sites of the different subunits by a lipoyl moiety, bound to a lysine residue from the E2 polypeptide.

The E1 subunit of 2-oxoglutarate dehydrogenase catalyses the decarboxylation of this compound in a thiamine pyrophosphate-dependent manner, transferring the resultant succinyl group onto the liposyl moiety bound to the E2 subunit. The E1 ortholog from Corynebacterium glutamicum (Brevibacterium flavum) is unusual in having an N-terminal extension that resembles the E2 component of 2-oxoglutarate dehydrogenase enzyme.
PD-(D/E)XK endonuclease-like domain superfamily (PDDEXK-like_dom_sf)
Type: Homologous_superfamily

This entry represent a PD-(D/E)XK endonuclease-like domain superfamily . PD-(D/E)XK nucleases constitute a large and highly diverse superfamily of enzymes that display little sequence similarity. However, they share a common core fold and a few critical active site residues . This domain can be found at the C terminus of nuclease/helicase AddA, AddB, and RecB.

There are two classes of helicase-nuclease complex involved in the initiation step for recombinational repair. AddAB-type enzymes (also called RexAB) are found mainly in Gram-positive bacteria, whereas heterotrimeric RecBCD-type enzymes are found mainly in Gram-negative bacteria . The RecBCD holoenzyme has a single nuclease domain found in RecB . Exodeoxyribonuclease V, or RecBCD holoenzyme, is a multifunctional nuclease with potent ATP-dependent exodeoxyribonuclease activity. Ejection of RecD, as occurs at chi recombinational hotspots, cripples exonuclease activity in favor of recombinagenic helicase activity. All proteins in this family for which functions are known are DNA-DNA helicases that are used as part of an exonuclease-helicase complex (made up of RecBCD homologues) that function to generate substrates for the initiation of recombination and recombinational repair. The complex catalyses exonucleolytic cleavage in either the 5' to 3' or 3' to 5' direction to yield 5-phosphooligonucleotides in the presence of ATP .

This superfamily includes phage-type exonucleases (

), the C-terminal domain of Exonuclease/helicase subunit RexA and RexB and RecB exodeoxyribonuclease V exonuclease (

), which are closely related in sequence and structure, containing a restriction enzyme-like core fold.

Exonuclease from Bacteriophage lambda facilitates phage DNA recombination through the double-strand break repair (DSBR) and single-strand annealing pathways; it is also important for the late, rolling-circle mode of lambda DNA replication. This magnesium-dependent enzyme catalyses the exonucleolytic cleavage of DNA in the 5'- to 3'-direction to yield nucleoside 5'-phosphates. Lambda exonuclease is a trimer of three subunits that form a toroid structure with a tapered channel passing through the middle .
NusB antitermination factor (NusB_fam)
Type: Family

The NusB protein is involved in the regulation of rRNA biosynthesis by transcriptional antitermination. The antitermination proteins of Escherichia coli are recruited in the replication cycle of Bacteriophage lambda, where they play an important role in switching from the lysogenic to the lytic cycle. The solution structure indicates that the protein folds into an α/α-helical topology consisting of six helices; the arginine-rich N terminus appears to be disordered .
Branched-chain amino acid transport, permease (Brnchd-chn_aa_trnsp_permease)
Type: Family

This entry includes some uncharacterised bacterial proteins and the branched-chain amino acid transport protein AzlC encoded by azlC gene, which is part of the azl operon, involved in branched-chain amino acid transport . AzlCD is a bipartite histidine exporter consisting of AzlC and AzlD subunits . Overexpression of this gene results in resistance to a leucine analogue, 4-azaleucine.
Methylglyoxal synthase-like domain (MGS-like_dom)
Type: Domain

Methylglyoxal synthase (MGS,

), which catalyses the conversion of dihydroxyacetone phosphate (DHAP) to methylglyoxal (MG) and inorganic phosphate, has been found in many organisms, including enteric bacteria, some gram-positive bacteria, a number of archaebacteria, several yeast species and goat liver .

The main core of the MGS-like domain, a modified 'Rossmann' fold, is characterised by a five stranded parallel β-sheet flanked on either side by three and five α-helices, respectively . MGS-like domains share a conserved phosphate binding site .
PRD domain (PRD)
Type: Domain

Transcriptional antiterminators and activators containing phosphoenolpyruvate: sugar phosphotransferase system (PTS) regulation domains (PRDs) form a class of bacterial regulatory proteins whose activity is modulated by phosphorylation. These regulators stimulate the expression of genes and operons involved in carbohydrate metabolism.

PRD-containing proteins are involved in the regulation of catabolic operons in Gram-positive and Gram-negative bacteria and are often characterised by a short N-terminal effector domain that binds to either RNA (CAT-RBD for antiterminators,

) or DNA (for activators), and a duplicated PRD module which is phosphorylated on conserved histidines by the sugar phosphotransferase system (PTS) in response to the availability of carbon source. The phosphorylations are thought to modify the stability of the dimeric proteins and thereby the RNA- or DNA-binding activity of the effector domain .
S-adenosyl-L-methionine-dependent methyltransferase ML2640-like (SAM_mthyl_Trfase_ML2640-like)
Type: Family

This family represents a set of probable methyltransferases, including ML2640 from Mycobacterium leprae, which has SAM-methyltransferase activity .
Carbohydrate kinase PfkB (PfkB_dom)
Type: Domain

This domain is found in a variety of carbohydrate and pyrimidine kinases. It is found in phosphomethylpyrimidine kinase (

), which is part of the thiamine pyrophosphate (TPP) synthesis pathway -TPP being an essential cofactor for many enzymes . It is also found in 2-keto-3-deoxygluconate kinase, which is a component of the Entner-Doudoroff pathway in hyperthermophilic archaea .
Urease alpha-subunit, N-terminal domain (Urease_alpha_N_dom)
Type: Domain

Urease (urea amidohydrolase,

) catalyses the hydrolysis of urea to form ammonia and carbamate. The subunit composition of urease from different sources varies , but each holoenzyme consists of four structural domains : three structural domains and a nickel-binding catalytic domain common to amidohydrolases . Urease is unique among nickel metalloenzymes in that it catalyses a hydrolysis rather than a redox reaction. In Helicobacter pylori, the gamma and beta domains are fused and called the alpha subunit (

). The catalytic subunit (called beta or B) has the same organisation as the Klebsiella alpha subunit. Jack bean (Canavalia ensiformis) urease has a fused gamma-beta-alpha organisation (

).

The N-terminal domain is a composite domain and plays a major trimer stabilising role by contacting the catalytic domain of the symmetry related alpha-subunit .
GH15-like domain (GH15-like)
Type: Domain

This entry represents a domain found in glycoside hydrolase family 15 members and in phosphorylase b kinase regulatory chains alpha and beta .

Glycoside hydrolase family 15

comprises enzymes with several known activities; glucoamylase (

); alpha-glucosidase (

); glucodextranase (

).
Catalase core domain (Catalase_core)
Type: Domain

Catalases (

) are antioxidant enzymes that catalyse the conversion of hydrogen peroxide to water and molecular oxygen, serving to protect cells from its toxic effects . Hydrogen peroxide is produced as a consequence of oxidative cellular metabolism and can be converted to the highly reactive hydroxyl radical via transition metals, this radical being able to damage a wide variety of molecules within a cell, leading to oxidative stress and cell death. Catalases act to neutralise hydrogen peroxide toxicity, and are produced by all aerobic organisms ranging from bacteria to man. Most catalases are mono-functional, haem-containing enzymes, although there are also bifunctional haem-containing peroxidase/catalases (

) that are closely related to plant peroxidases, and non-haem, manganese-containing catalases (

) that are found in bacteria . Based on a phylogenetic analysis, catalases can be classified into clade 1, 2 and 3. Clade 1 contains small subunit catalases from plants and a subset of bacteria; clade 2 contains large subunit catalases from fungi and a second subset of bacteria; and clade 3 contains small subunit catalases from bacteria, fungi, protists, animals, and plants .

This entry represent the core-forming domain of mono-functional, haem-containing catalases. It does not cover the region that carries an immune-responsive amphipathic octa-peptide that is found in the C-terminal of some catalases (

).
p53, DNA-binding domain (p53_DNA-bd)
Type: Domain

This domain is found in p53 transcription factors, where it is responsible for DNA-binding. The DNA-binding domain acts to clamp, or in the case of TonEBP, encircle the DNA target in order to stabilise the protein-DNA complex . Protein interactions may also serve to stabilise the protein-DNA complex, for example in the STAT-1 dimer the SH2 (Src homology 2) domain in each monomer is coupled to the DNA-binding domain to increase stability . The DNA-binding domain consists of a β-sandwich formed of 9 strands in 2 sheets with a Greek-key topology. This structure is found in many transcription factors, often within the DNA-binding domain.

The p53 tumour suppressor is a protein found in increased amounts in a wide variety of transformed cells. It is also detectable in many proliferating non-transformed cells, but it is undetectable or present at low levels in resting cells. It is frequently mutated or inactivated in many types of cancer. p53 seems to act as a tumour suppressor in some, but probably not all, tumour types. p53 has been implicated in cell cycle regulation, particularly in the monitoring of genomic DNA integrity prior to replication; for this reason it has been dubbed 'guardian of the genome'. p53 can be divided into different functional domains: an N-terminal transactivation domain (

), a proline-rich domain, a DNA-binding domain (

) which contains a conserved site (

), a tetramerisation domain (

) and a C-terminal regulatory region.
Sorbitol phosphotransferase enzyme II, N-terminal (PTS_EIIBC_GUT_N)
Type: Domain

Bacterial PTS transporters transport and concomitantly phosphorylate their sugar substrates, and typically consist of multiple subunits or protein domains. The Man family is unique in several respects among PTS permease families.

It is the only PTS family in which members possess a IID protein.

It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue.

Its permease members exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars.

The Gut family consists only of glucitol-specific permeases, but these occur both in Gram-negative and Gram-positive bacteria. Escherichia coli consists of IIA protein, a IIC protein and a IIBC protein.

This entry represents the N-terminal conserved region of the IIBC component.