SII-SWORD/CoKE huggingface dataset:
DNA topoisomerase IB, active site (TopoIB_AS)
Type: Active_site

This entry represents the region around the active site tyrosine in eukaryotes and poxvirus topoisomerases IB (Topo IB).

DNA topoisomerase I (

) is one of the two types of enzyme that catalyze the interconversion of topological DNA isomers. Type I topoisomerases act by catalyzing the transient breakage of DNA, one strand at a time, and the subsequent rejoining of the strands. When a eukaryotic type 1 topoisomerase breaks a DNA backbone bond, it simultaneously forms a protein-DNA link where the hydroxyl group of a tyrosine residue is joined to a 3'-phosphate on DNA, at one end of the enzyme-severed DNA strand. In eukaryotes and poxvirus topoisomerases I, there are a number of conserved residues in the region around the active site tyrosine

Type I topoisomerases are ATP-independent enzymes (except for reverse gyrase), and can be subdivided according to their structure and reaction mechanisms: type IA (Topo IA; bacterial and archaeal topoisomerase I, topoisomerase III and reverse gyrase) and type IB (Topo IB; eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA. This function is vital for the processes of replication, transcription, and recombination. Unlike Topo IA enzymes, Topo IB enzymes do not require a single-stranded region of DNA or metal ions for their function. The type IB family of DNA topoisomerases includes eukaryotic nuclear topoisomerase I, topoisomerases of poxviruses, and bacterial versions of Topo IB . They belong to the superfamily of DNA breaking-rejoining enzymes, which share the same fold in their C-terminal catalytic domain and the overall reaction mechanism with tyrosine recombinases . The C-terminal catalytic domain in topoisomerases is linked to a divergent N-terminal domain that shows no sequence or structure similarity to the N-terminal domains of tyrosine recombinases .

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 .
DNA topoisomerase, type IIA, conserved site (TopoIIA_CS)
Type: Conserved_site

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 .

DNA topoisomerase II (

) is one of the two types of enzyme that catalyze the interconversion of topological DNA isomers. Type II topoisomerases are ATP-dependent and act by passing a DNA segment through a transient double-strand break. Topoisomerase II is found in phages, archaebacteria, prokaryotes, eukaryotes, and in African Swine Fever virus (ASF). Bacteriophage T4 topoisomerase II consists of three subunits (the product of genes 39, 52 and 60). In prokaryotes and in archaebacteria the enzyme, known as DNA gyrase, consists of two subunits (genes GyrA and GyrB). In some bacteria, a second type II topoisomerase has been identified; it is known as topoisomerase IV and is required for chromosome segregation, it also consists of two subunits (genes parC and parE). In eukaryotes, type II topoisomerase is a homodimer.
Isocitrate lyase/phosphorylmutase, conserved site (Isocitrate_lyase_ph_CS)
Type: Conserved_site

Isocitrate lyase (

) is an enzyme that catalyzes the conversion of isocitrate to succinate and glyoxylate. This is the first step in the glyoxylate bypass, an alternative to the tricarboxylic acid cycle in bacteria, fungi and plants. A cysteine, a histidine and a glutamate or aspartate have been found to be important for the enzyme's catalytic activity. Only one cysteine residue is conserved between the sequences of the fungal, plant and bacterial enzymes; it is located in the middle of a conserved hexapeptide.

Other enzymes also belong to this family including carboxyvinyl-carboxyphosphonate phosphorylmutase (

) which catalyses the conversion of 1-carboxyvinyl carboxyphosphonate to 3-(hydrohydroxyphosphoryl) pyruvate carbon dioxide, and phosphoenolpyruvate mutase (

), which is involved in the biosynthesis of phosphinothricin tripeptide antiobiotics.
DNA/RNA non-specific endonuclease, active site (DNA/RNA_endonuclease_AS)
Type: Active_site

A family of bacterial and eukaryotic endonucleases

share the following characteristics: they act on both DNA and RNA, cleave double-stranded and single-stranded nucleic acids and require a divalent ion such as magnesium for their activity. A histidine has been shown to be essential for the activity of the Serratia marcescens nuclease. This residue is located in a conserved region which also contains an aspartic acid residue that could be implicated in the binding of the divalent ion.
Mini-chromosome maintenance, conserved site (MCM_CS)
Type: Conserved_site

MCM proteins are DNA-dependent ATPases required for the initiation of eukaryotic DNA replication . In eukaryotes there is a family of six proteins, MCM2 to MCM7. They were first identified in yeast where most of them have a direct role in the initiation of chromosomal DNA replication by interacting directly with autonomously replicating sequences (ARS). They were thus called minichromosome maintenance proteins, MCM proteins .

This family is also present in the archebacteria in 1 to 4 copies. Methanocaldococcus jannaschii (Methanococcus jannaschii) has four members, MJ0363, MJ0961, MJ1489 and MJECL13.

The "MCM motif" contains Walker-A and Walker-B type nucleotide binding motifs. The diagnostic sequence defining the MCMs is IDEFDKM. Only Mcm2 (aka Cdc19 or Nda1) has been subjected to mutational analysis in this region, and most mutations abolish its activity . The presence of a putative ATP-binding domain implies that these proteins may be involved in an ATP-consuming step in the initiation of DNA replication in eukaryotes.

The MCM proteins bind together in a large complex . Within this complex, individual subunits associate with different affinities, and there is a tightly associated core of Mcm4 (Cdc21), Mcm6 (Mis5) and Mcm7 . This core complex in human MCMs has been associated with helicase activity
in vitro
, leading to the suggestion that the MCM proteins are the eukaryotic replicative helicase.

Schizosaccharomyces pombe (Fission yeast) MCMs, like those in metazoans, are found in the nucleus throughout the cell cycle. This is in contrast to the Saccharomyces cerevisiae (Baker's yeast) in which MCM proteins move in and out of the nucleus during each cell cycle. The assembly of the MCM complex in S. pombe is required for MCM localisation, ensuring that only intact MCM complexes remain in the nucleus .

The signature pattern used in this entry represents a perfectly conserved region that is a special version of the B motif found in ATP-binding proteins.
Glycoside hydrolase, family 29, conserved site (Glyco_hydro_29_CS)
Type: Conserved_site

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.

O-Glycosyl hydrolases family 29 (

) encompasses alpha-L-fucosidases (

) , which is a lysosomal enzyme responsible for hydrolysing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins. Alpha-L-fucosidase is responsible for hydrolysing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins.

Fucosylated glycoconjugates are involved in numerous biological events, making alpha-l-fucosidases, the enzymes responsible for their processing, critically important. Deficiency in alpha-l-fucosidase activity is associated with fucosidosis, a lysosomal storage disorder characterised by rapid neurodegeneration, resulting in severe mental and motor deterioration . The enzyme is a hexamer and displays a two-domain fold, composed of a catalytic (β/α)(8)-like domain and a C-terminal β-sandwich domain .

Drosophila melanogaster spermatozoa contains an alpha-l-fucosidase that might be involved in fertilisation by interacting with alpha-l-fucose residues on the micropyle of the eggshell . In human sperm, membrane-associated alpha-l-fucosidase is stable for extended periods of time, which is made possible by membrane domains and compartmentalisation. These help preserve protein integrity .

This entry represents a short conserved sequence found in alpha-L-fucosidases that includes a cysteine that is suspected, though not proven, to be the active site residue.
Rubredoxin, iron-binding site (Rubredoxin_Fe_BS)
Type: Binding_site

Rubredoxin is a low molecular weight iron-containing protein involved in electron transfer , sometimes replacing ferredoxin as an electron carrier . It is found in bacteria, archaea and plants.

The 3-D structures of a number of rubredoxins have been solved . The fold belongs to the α+β class, with 2 α-helices and 2-3 β-strands. Its active site contains an iron ion which is co-ordinated by the sulphurs of four conserved cysteine residues forming an almost regular tetrahedron . The conserved cysteines reside on two loops, which are the most conserved regions of the protein. In addition, a ring of acidic residues in the proximity of the [Fe(Cys)4] centre is also well-conserved .

This entry represents a conserved region which includes two of the cysteine residues that bind the iron atom.
Prephenate dehydratase, conserved site (Preph_deHydtase_CS)
Type: Conserved_site

Prephenate dehydratase (

, PDT) catalyses the decarboxylation of prephenate to phenylpyruvate. In microorganisms it is part of the terminal pathway of phenylalanine biosynthesis. In some bacteria such as Escherichia coli PDT is part of a bifunctional enzyme (P-protein) that also catalyses the transformation of chorismate into prephenate (chorismate mutase,

,

) while in other bacteria it is a monofunctional enzyme. In the archaea Archaeoglobus fulgidus is part of a trifunctional enzyme . The sequence of monofunctional PDT aligns well with the C-terminal part of P-proteins .

This entry represents two conserved regions. The first contains a conserved threonine which appears to be essential for the activity of the enzyme in E. coli . The second region is located in the regulatory (Phe binding) region in the part C-terminal to PDT and this includes a conserved glutamate.
SiaC family regulatory phosphoprotein (SiaC)
Type: Domain

This entry represents a domain of the SiaC family regulatory phosphoprotein, which undergoes a regulatory phosphorylation at Thr-68 of founder protein PA0170 from Pseudomonas aeruginosa, but in more distant homologues, T can be S. Also, it is part of motif NTSS, so may contain more than one phosphorylation site. Phosphorylation causes regulatory change to protein-protein interaction, in a pathway that seems broadly distributed, involves a diguanylate cyclase, and in the case of Pseudomonas aeruginosa affects aggregation and biofilm formation responses .
Protein of unknown function DUF1993 (DUF1993)
Type: Family

This family of proteins are functionally uncharacterised.
Forkhead box protein, C-terminal (Forkhead_box_C)
Type: Domain

This presumed domain is found in the C-terminal region of Hepatocyte Nuclear Factor 3 alpha and beta chains. Its specific function is uncertain. The N-terminal region of this presumed domain contains an EH1 (engrailed homology 1) motif, that is characterised by the FxIxxIL sequence .
Tetracycline regulation of excision, RteC (Tet_reg_excision_RteC)
Type: Family

Human colonic Bacteroides species harbour a family of large conjugative transposons, called tetracycline resistance (Tcr) elements. Activities of these elements are enhanced by pregrowth of bacteria in medium containing tetracycline, indicating that at least some Tcr element genes are regulated by tetracycline. An insertional disruption in the rteC gene abolished self-transfer of the Tcr element to Bacteroides recipients, indicating that the gene was essential for self-transfer .
Domain of unknown function DUF1996 (DUF1996)
Type: Domain

This family of proteins are functionally uncharacterised.
Chromophore lyase CpcS/CpeS (CpcS/CpeS)
Type: Family

This entry represents the CpcS/CpeS biliprotein lyase family, which have been shown to covalently attach chromophores to cystiene residue(s) of phycobiliproteins . In the chromatically adapting cyanobacterium Fremyella diplosiphon, the proteins have been shown to be induced by green light, as part of the cpeCDESTR operon .
Peptidoglycan binding domain (Peptidoglycan-bd_3)
Type: Domain

This entry represents a peptidoglycan binding domain frequently found at the C terminus of proteins containing a N-terminal

domain, predominantly in bacteria and virus, including Glycoside hydrolase family 108 protein from Salmonella typhi (TtsA,

). TtsA is a specific muramidase that facilitates toxin transport through the peptidoglycan layer. The C-terminal domain confers substrate specificity and typhoid toxin secretion functions. It shows of 6 antiparallel α-helices that organise into a helix bundle .
Helicase HerA, barrel domain (HerA_barrel_dom)
Type: Domain

The HAS barrel is named after HerA, which is a DNA helicase able to utilise either 3' or 5' single-stranded DNA extensions for loading and subsequent DNA duplex unwinding . It forms a complex with NurA nuclease, this complex has the 5'-3' DNA end resection activity and is essential for cell viability in the crenarchaeon Sulfolobus islandicus . This domain is found in the N-terminal region of HerA and is implicated in the assembly of the catalytic toroid and docking of accessory subunits .
Aspartyl-phosphate phosphatase Spo0E-like (Spo0E-like)
Type: Family

Spo0E is an aspartyl-phosphate phosphatase which specifically dephosphorylates the sporulation transcription factor Spo0A-P and negatively regulates the sporulation initiation pathway in order to control the proper timing of sporulation . The structure of Spo0E has revealed an anti-parallel α-helical structure .

Spore formation is an extreme response to starvation and can also be a component of disease transmission. Sporulation is controlled by an expanded two-component system where starvation signals result in sensor kinase activation and phosphorylation of the master sporulation response regulator Spo0A. Phosphatases such as Spo0E dephosphorylate Spo0A thereby inhibiting sporulation .
FtsK gamma domain (Ftsk_gamma)
Type: Domain

This domain directs oriented DNA translocation and forms a winged helix structure . Mutated proteins with substitutions in the FtsK gamma DNA-recognition helix are impaired in DNA binding .
Protein 9b, Betacoronavirus (Protein_9b_Betacoronavirus)
Type: Family

This is a family of proteins found in SARS and SARS-like coronaviruses. It includes Protein 9b from SARS coronavirus 2 (SARS-CoV-2), Human SARS coronavirus (SARS-CoV) and Bat coronaviruses.

Protein 9b is one of 8 accessory proteins in SARS-CoV . The gene (ORF 9b, also known as ORF13) that encodes this protein is included within the nucleocapsid (N) gene (alternative ORF) . Data suggest that protein 9b is a structural component of SARS-CoV virions and functions as an unusual lipid binding protein .

SARS-CoV ORF-9b has been shown to localise to the outer mitochondrial membrane and to target mitochondrial antiviral signalling proteins (MAVS), suppressing innate immunity . Antibodies against SARS-CoV ORF-9b have been found in patients, demonstrating that it is produced during infection .

Protein 9b from SARS CoV comprises 98 amino acids. Its structure has a novel fold which forms a dimeric tent-like β structure with an amphipathic surface, and a central hydrophobic cavity that binds lipid molecules . This cavity is likely to be involved in membrane attachment .

Protein 9b is a group-specific protein of SARS coronavirus (CoV). The sequence of ORF-9b is well conserved in different SARS isolates, however, there is little homology between Protein 9b from SARS-CoV and the I protein (Protein 9b homologue) present in other coronaviruses .
Adhesion protein FadA (Adhesion_FadA)
Type: Family

FadA (Fusobacterium adhesin A) is an adhesin which forms two α helices.
KICSTOR subunit 2 (KICS_2)
Type: Family

This entry includes KICSTOR subunit 2 (KICS2, also known as C12orf66-like) proteins. Human KICS2 is part of the KICSTOR complex that functions in the amino acid-sensing branch of the TORC1 signalling pathway .
Btz domain (Btz_dom)
Type: Domain

This domain is found on CASC3 (cancer susceptibility candidate gene 3 protein, also known as MLN51) which is also known as Barentsz (Btz). CASC3 is a component of the EJC (exon junction complex) which is a complex that is involved in post-transcriptional regulation of mRNA in metazoa. The complex is formed by the association of four proteins (eIF4AIII, Barentsz, Mago, and Y14), mRNA, and ATP. This domain wraps around eIF4AIII and stacks against the 5' nucleotide .
Domain of unknown function DUF2004 (DUF2004)
Type: Domain

This is entry represents a domain of unknown function in archaeal proteins. The structure of one of the proteins in this family has revealed a novel α-β fold .
AbiEi antitoxin C-terminal domain (AbiEi_C)
Type: Domain

AbiEi_1 is the cognate antitoxin of the type IV toxin-antitoxin 'innate immunity' bacterial abortive infection (Abi) system that protects bacteria from the spread of a phage infection. The Abi system is activated upon infection with phage to abort the cell thus preventing the spread of phage through viral replication. There are some 20 or more Abis, and they are predominantly plasmid-encoded lactococcal systems. TA, toxin-antitoxin, systems on plasmids function by killing cells that lose the plasmid upon division. AbiE phage resistance systems function as novel Type IV TAs and are widespread in bacteria and archaea .
Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus (Spike_S1_RBD_bCoV)
Type: Domain

The CoV Spike (S) protein is an envelope glycoprotein that plays the most important role in viral attachment, fusion, and entry into host cells, and serves as a major target for the development of neutralizing antibodies, inhibitors of viral entry, and vaccines. It is synthesised as a precursor protein that is cleaved into an N-terminal S1 subunit (~700 amino acids) and a C-terminal S2 subunit (~600 amino acids) that mediates attachment and membrane fusion, respectively. Three S1/S2 heterodimers assemble to form a trimer spike protruding from the viral envelope. The S1 subunit contains a receptor-binding domain (RBD), while the S2 subunit contains a hydrophobic fusion peptide and two heptad repeat regions. S1 contains two structurally independent domains, the N-terminal domain (NTD) and the C-terminal domain (C-domain). Depending on the virus, either the NTD or the C-domain can serve as the receptor-binding domain (RBD). Most CoVs, including SARS-CoV-2, SARS-CoV, and MERS-CoV use the C-domain to bind their receptors. However, CoV such as mouse hepatitis virus (MHV) uses the NTD to bind its receptor, mouse carcinoembryonic antigen related cell adhesion molecule 1a (mCEACAM1a). The S1 NTD contributes to the Spike trimer interface .

This domain corresponds to the receptor-binding domain (RBD) of the Spike S1 subunit which binds to angiotensin-converting enzyme 2 (ACE2) in respiratory syndrome coronavirus (SARS-CoV) , but not in some bat-derived coronaviruses (BatCoV) .

This domain is composed of a core and an external subdomain. During evolution, the core subdomain is structurally preserved, whereas the external subdomain folds into variant structures to engage different receptors. The most conserved part lies in the core-centre sheet that is composed of five antiparallel strands and functions as the scaffold of the core subdomain. Additional conserved elements include the core-centre helices and core-peripheral structures. Characteristic cysteine residues form three disulfide bonds in the core subdomain, further stabilizing the core structure from the interior .
Lipid A 3-O-deacylase-related (Lipid-A_deacylase-rel)
Type: Family

PagL is an outer membrane protein with lipid A 3-O-deacylase activity. It forms an 8 stranded β barrel structure .
Domain of unknown function DUF2007 (DUF2007)
Type: Domain

This domain of unknown function is found in a variety of bacterial sequences.
Centromere protein X (CENP-X)
Type: Family

Centromere protein X (CENP-X) is a component of several different complexes, including the multisubunit FA complex, the heterotetrameric CENP-T-W-S-X complex and the APITD1/CENPS complex.
Non-canonical E2 ubiquitin-conjugating enzyme (E2_Ub-conjug_enz)
Type: Family

This entry describes a family of non-canonical E2 ubiquitin-conjugating proteins that lack the typical HPN motif characteristic of conventional E2 enzymes, including

from Plasmodium falciparum and similar proteins mainly from in Apicomplexan parasites, fungi and some amoeba species. These proteins show a C-terminal domain (

) that possess a highly conserved catalytic cysteine residue, which forms a thioester bond with ubiquitin.The N-terminal region contains coiled helices involved in protein-protein interactions with other ubiquitin pathway components like Rbx1 .
Frequency clock protein (FRQ)
Type: Family

Frequency (FRQ) is a key circadian clock component that is involved in the generation of biological rhythms in Neurospora crassa . It plays a role in rhythm stability, period length, and temperature compensation. FRQ behaves as a negative element in the circadian transcriptional loop . The protein has been shown to interact with itself via a coiled-coil .
C630.06c-like (C630.06c-like)
Type: Family

This protein family includes the uncharacterised nucleolar protein C630.06c from Schizosaccharomyces pombe and similar fungal proteins. C630.06c is an orthologue of the conserved eukaryotic protein Custos, implicated in cell growth or cell division .
SPIN90/Ldb17, leucine-rich domain (SPIN90/Ldb17_LRD)
Type: Domain

This is the conserved leucine-rich domain (LRD) within the C-terminal domain of SPIN90 (also known as NCK interacting protein with SH3 domain (NCKIPSD)) from animals, Ldb17 from budding yeasts and Dip1 from fission yeasts . Ldb17 is involved in the regulation of endocytosis in yeast . SPIN90 is an F-actin binding protein that regulates actin polymerization and endocytosis . It associates with and activates the Arp2/3 complex, without requiring a preformed actin filament . This LRD, within the C-terminal armadillo repeat (ARM) domain of SPIN90, is important for activation of Arp2/3 complex .