SII-SWORD/CoKE huggingface dataset:
DNA topoisomerase, type IA, zn finger (Topo_IA_Znf)
Type: Domain

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 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 .

This entry represents the zinc-finger domain found in type IA topoisomerases, including bacterial and archaeal topoisomerase I and III enzymes, and in eukaryotic topoisomerase III enzymes. Escherichia coli topoisomerase I proteins contain five copies of a zinc-ribbon-like domain at their C terminus, two of which have lost their cysteine residues and are therefore probably not able to bind zinc . This domain is still considered to be a member of the zinc-ribbon superfamily despite not being able to bind zinc.
DNA topoisomerase I, eukaryotic-type (TopoI_euk)
Type: Domain

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 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 .

This entry represents the C-terminal region of DNA topoisomerase I enzymes from eukaryotes (type IB enzymes). This region covers both the catalytic core and the DNA-binding domains.

Human topoisomerase I has been shown to be inhibited by camptothecin (CPT), a plant alkaloid with antitumour activity . The crystal structures of human topoisomerase I comprising the core and carboxyl-terminal domains in covalent and noncovalent complexes with 22-base pair DNA duplexes reveal an enzyme that "clamps" around essentially B-form DNA. The core domain and the first eight residues of the carboxyl-terminal domain of the enzyme, including the active-site nucleophile tyrosine-723, share significant structural similarity with the bacteriophage family of DNA integrases. A binding mode for the anticancer drug camptothecin has been proposed on the basis of chemical and biochemical information combined with the three-dimensional structures of topoisomerase I-DNA complexes .
Ethanolamine utilization microcompartment shell protein, Lmo1185-like (Lmo1185-like)
Type: Family

This entry represents a family of proteins from firmicutes, including Lmo1185 from Listeria monocytogenes (

). Members are trimeric shell proteins encoded in ethanolamine utilization microcompartment operons . This family is closely related to the PduT protein encoded in propane-diol operons.
Uncharacterised protein AF0941 (Uncharacterised_AF0941)
Type: Family

This entry represents the hypothetical protein AF_0941 from the hyperthermophilic sulphate-reducing archaeon Archaeoglobus fulgidus. The structure of this protein consists of several α-helices arranged in an orthogonal bundle.
Circadian clock KaiC, bacteria (Circadian_KaiC_bact)
Type: Family

The circadian clock protein KaiC, is encoded in the kaiABC operon that forms the KaiABC oscillator complex which controls circadian rhythms and may be universal in Cyanobacteria . Each member contains two copies of the KaiC domain, which is also found in other proteins. KaiC performs autophosphorylation and acts as its own transcriptional repressor. The complex composition changes during the circadian cycle to control KaiC phosphorylation. KaiA stimulates KaiC autophosphorylation, while KaiB sequesters KaiA, leading to KaiC autodephosphorylation . Clock output pathways impact the RpaA transcriptional regulator. KaiC enhances the autophosphorylation activity of SasA, which then transfers its phosphate group to RpaA to activate it. KaiB and KaiC together enhance the phospho-RpaA dephosphatase activity of CikA.Kai proteins (KaiA and KaiC) appear to positively and negatively regulate kaiBC transcription which is consistent with a transcription/translation oscillatory (TTO) feedback model, believed to be at the core of all self-sustained circadian timers. However, the cyanobacterial circadian clock is able to function without de novo synthesis of clock gene mRNAs and the clock proteins, and the period is accurately determined without TTO feedback and the system is also temperature-compensated. It has been demonstrated that these three purified proteins form a temperature-compensated molecular oscillator in vitro that exhibits rhythmic phosphorylation and dephosphorylation of KaiC .

A negative-stain electron microscopy study of Synechococcus elongatus (Thermosynechococcus elongatus) and Thermosynechococcus elongatus BP-1 KaiA-KaiC complexes in combination with site-directed mutagenesis reveals that KaiA binds exclusively to the CII half of the KaiC hexamer. The EM-based model of the KaiA-KaiC complex reveals protein-protein interactions at two sites: the known interaction of the flexible C-terminal KaiC peptide with KaiA, and a second postulated interaction between the apical region of KaiA and the ATP binding cleft on KaiC. This model brings KaiA mutation sites that alter clock period or abolish rhythmicity into contact with KaiC and suggests how KaiA might regulate KaiC phosphorylation .

This entry also includes KaiC3 which represents a nonstandard KaiC homologue that seems to be linked to dark adaption of Synechocystis cells, but is not as essential as the core oscillator KaiAB1C1 for the circadian cycle .
Methylamine/Aralkylamine dehydrogenase light chain, C-terminal domain (MADH/AADH_Ltc_C_dom)
Type: Domain

Aralkylamine dehydrogenase light chain and methylamine dehydrogenase light chain are aromatic amine dehydrogenases that form heterotetramers with their respective heavy chains, and catalyse the oxidative deamination of amines to their corresponding aldehydes.

This entry represents a conserved domain found towards the C terminus of these proteins.
DNA topoisomerase, type IIA, subunit B, domain 2 (Topo_IIA_bsu_dom2)
Type: Domain

Type IIA topoisomerases together manage chromosome integrity and topology in cells. 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 topoisomerase II forms a homodimer that is equivalent to the bacterial heterotetramer. There are four functional domains in topoisomerase II: domain 1 (N-terminal of gyrB) is an ATPase, domain 2 (C-terminal of gyrB) is responsible for subunit interactions, domain 3 (N-terminal of gyrA) is responsible for the breaking-rejoining function through its capacity to form protein-DNA bridges, and domain 4 (C-terminal of gyrA) is able to non-specifically bind DNA .

Topoisomerase IV primarily decatenates DNA and relaxes positive supercoils, which is important in bacteria, where the circular chromosome becomes catenated, or linked, during replication . Topoisomerase IV consists of two polypeptide subunits, parE and parC, where parC is homologous to gyrA and parE is homologous to gyrB.

This entry represents the second domain found in subunit B (gyrB and parE) of bacterial gyrase and topoisomerase IV, and the equivalent N-terminal region in eukaryotic topoisomerase II composed of a single polypeptide.

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 mismatch repair protein, S5 domain 2-like (DNA_mismatch_S5_2-like)
Type: Domain

This domain is found in MutL and homologues and is characterised by a ribosomal protein S5 domain 2-like fold .

The dimeric MutL protein has a key function in communicating mismatch recognition by MutS to downstream repair processes. Mismatch repair contributes to the overall fidelity of DNA replication by targeting mispaired bases that arise through replication errors during homologous recombination and as a result of DNA damage. It involves the correction of mismatched base pairs that have been missed by the proofreading element of the DNA polymerase complex .
Ribonucleotide reductase large subunit, N-terminal (RNR_lsu_N)
Type: Domain

Ribonucleotide reductase (RNR,

) catalyses the reductive synthesis of deoxyribonucleotides from their corresponding ribonucleotides. It provides the precursors necessary for DNA synthesis. RNRs divide into three classes on the basis of their metallocofactor usage. Class I RNRs, found in eukaryotes, bacteria, bacteriophage and viruses, use a diiron-tyrosyl radical, Class II RNRs, found in bacteria, bacteriophage, algae and archaea, use coenzyme B12 (adenosylcobalamin, AdoCbl). Class III RNRs, found in anaerobic bacteria and bacteriophage, use an FeS cluster and S-adenosylmethionine to generate a glycyl radical. Many organisms have more than one class of RNR present in their genomes.

Ribonucleotide reductase is an oligomeric enzyme composed of a large subunit (700 to 1000 residues) and a small subunit (300 to 400 residues) - class II RNRs are less complex, using the small molecule B12 in place of the small chain .

The reduction of ribonucleotides to deoxyribonucleotides involves the transfer of free radicals, the function of each metallocofactor is to generate an active site thiyl radical. This thiyl radical then initiates the nucleotide reduction process by hydrogen atom abstraction from the ribonucleotide . The radical-based reaction involves five cysteines: two of these are located at adjacent anti-parallel strands in a new type of ten-stranded α/β-barrel; two others reside at the carboxyl end in a flexible arm; and the fifth, in a loop in the centre of the barrel, is positioned to initiate the radical reaction . There are several regions of similarity in the sequence of the large chain of prokaryotes, eukaryotes and viruses spread across 3 domains: an N-terminal domain common to the mammalian and bacterial enzymes; a C-terminal domain common to the mammalian and viral ribonucleotide reductases; and a central domain common to all three .
1-deoxy-D-xylulose 5-phosphate reductoisomerase, N-terminal (DXP_reductoisomerase_N)
Type: Domain

This domain is found at the N terminus of bacterial and plant 1-deoxy-D-xylulose 5-phosphate reductoisomerases. It is responsible for the binding to NADPH .

1-deoxy-D-xylulose 5-phosphate reductoisomerase synthesises 2-C-methyl-D-erythritol 4-phosphate from 1-deoxy-D-xylulose 5-phosphate in a single step by intramolecular rearrangement and reduction and is responsible for terpenoid biosynthesis in some organisms . In Arabidopsis thaliana 1-deoxy-D-xylulose 5-phosphate reductoisomerase is the first committed enzyme of the non-mevalonate pathway for isoprenoid biosynthesis. The enzyme requires Mn2+, Co2+ or Mg2+ for activity, with the first being most effective.

The structure of this enzyme has been solved, showing the protein forms a dimeric assembly and contains a metal ion in the active site .
Protein of unknown function DUF3199, YqbG (DUF3199_YqbG)
Type: Family

This entry represents the hypothetical protein YqbG from Bacillus species, as well as related proteins from other bacteria. YqbG exists as a monomer, consisting of four α-helices with a right-handed twist, arranged in a left-handed superhelix .
Phytochrome, central region (Phytochrome_cen-reg)
Type: Domain

Phytochrome belongs to a family of plant photoreceptors that mediate physiological and developmental responses to changes in red and far-red light conditions . Besides plants, they are widely represented in both photosynthetic and non-photosynthetic bacteria and are known in a variety of fungi. The protein undergoes reversible photochemical conversion between a biologically-inactive red light-absorbing form and the active far-red light-absorbing form. Phytochrome is a dimer of identical 124kDa subunits, each of which contains a linear tetrapyrrole chromophore, covalently-attached via a Cys residue.

This domain is found in the central region of phytochrome proteins. It is structurally related to the GAF domain

, which is generally located immediately N-terminal to this domain, but it carries an additional tongue-like hairpin loop between the fifth β-sheet and the sixth α-helix which functions to seal the chromophore pocket and stabilise the photoactivated far-red-absorbing state (Pfr) .
Phytochrome chromophore binding site (Phyto_chromo_BS)
Type: Binding_site

Phytochrome is a plant protein that acts as a regulatory photoreceptor and which mediates red-light effects on a wide variety of physiological and molecular responses. Phytochrome can undergo a reversible photochemical conversion between a biologically inactive red light-absorbing form and the active far-red light-absorbing form. Phytochrome is a dimer of identical 124 Kd subunits, each of which contains a covalently attached linear tetrapyrrole chromophore.

The chromophore is attached to a cysteine which is located in a highly conserved region that can be used as a signature pattern.

Synechocystis strain PCC 6803 hypothetical protein slr0473 contains a domain similar to that of plants phytochrome and seems to also bind a chromophore.
FG-GAP repeat (FG-GAP)
Type: Repeat

This region contains the extracellular repeat that is found in up to seven copies in alpha integrins and related proteins. It forms a 7-fold repeat that adopts a β-propeller structure . The repeat is called the FG-GAP repeat after two conserved motifs in the repeat . The FG-GAP repeats are found in the N terminus of integrin alpha chains, a region that has been shown to be important for ligand binding . A putative Ca2+ binding motif is found in some of the repeats. These repeats are found in multiple proteins from eukaryotes and bacteria and mediate diverse biological processes at both molecular and cellular levels, such as cell-cell interactions, host patogen recognition or innate immune responses.
Integrin alpha beta-propellor (Int_alpha_beta-p)
Type: Repeat

Integrins are cell adhesion molecules that mediate cell-extracellular matrix and cell-cell interactions. They contain both alpha and beta subunits. Alpha integrins are proposed to contain a domain containing a 7-fold repeat that adopts a β-propeller fold. Some of these domains contain an inserted von Willebrand factor type-A domain. Some repeats contain putative calcium-binding sites. The 7-fold repeat domain is homologous to a similar domain in phosphatidylinositol-glycan-specific phospholipase D.
Ribonuclease H-like domain (Ribonucl_H)
Type: Domain

This entry includes a variety of exonuclease proteins, such as Oligoribonuclease, ribonuclease T and the epsilon subunit of DNA polymerase III.

Ribonuclease T (

) is an enzyme found so far only in gamma-subdivision proteobacteria such as Escherichia coli and Xylella fastidiosa. Ribonuclease T is homologous to the DNA polymerase III alpha chain. It can liberate AMP from the common C-C-A terminus of uncharged tRNA. It appears also to be involved in RNA maturation. It also acts as a 3' to 5' single-strand DNA-specific exonuclease; it is distinctive for its ability to remove residues near a double-stranded stem. Ribonuclease T is a high copy suppressor in E. coli of a UV-repair defect caused by deletion of three other single-stranded DNA exonucleases .

Oligoribonuclease (Orn) is an essential 3'->5' exoribonuclease in Escherichia coli and other bacteria, specialising in the degradation of small oligoribonucleotides (2-5 nucleotides) to mononucleotides during mRNA decay. It ensures complete RNA turnover by hydrolysing these short RNA fragments, which accumulate lethally in its absence, disrupting cellular viability. Beyond mRNA processing, Orn plays a critical role in cyclic diguanylate (c-di-GMP) signalling by degrading the intermediate 5'-phosphoguanylyl-(3',5')-guanosine (pGpG), preventing its accumulation and subsequent inhibition of c-di-GMP phosphodiesterases. This activity regulates biofilm formation and virulence in pathogens like Pseudomonas aeruginosa. Structurally conserved across domains of life, Orn operates processively via a manganese-dependent mechanism, preferring substrates with free 3'-hydroxyl groups and exhibiting inverse activity dependence on oligomer length. Its dual role in RNA metabolism and signalling underscores its importance in maintaining cellular homeostasis .
Histone acetyltransferase HAT1, C-terminal (Hist_AcTrfase_HAT1_C)
Type: Homologous_superfamily

Histone acetylation is carried out by a class of enzymes known as histone acetyltransferases (HATs), which catalyse the transfer of an acetyl group from acetyl-CoA to the lysine
E
-amino groups on the N-terminal tails of histones . Early indication that HATs were involved in transcription came from the observation that in actively transcribed regions of chromatin, histones tend to be hyperacetylated, whereas in transcriptionally silent regions histones are hypoacetylated. The histone acetyltransferases are divided into five families. These include the Gcn5-related acetyltransferases (GNATs); the MYST (for `MOZ, Ybf2/Sas3, Sas2 and Tip60)-related HATs; p300/CBP HATs; the general transcription factor HATs, which include the TFIID subunit TAF250; and the nuclear hormone-related HATs SRC1 and ACTR (SRC3). The GCN5-related N-acetyltransferase superfamily includes such enzymes as the histone acetyltransferases GCN5 and Hat1, the elongator complex subunit Elp3, the mediator-complex subunit Nut1, and Hpa2 .

Many GNATs share several functional domains, including an N-terminal region of variable length, an acetyltransferase domain that encompasses the conserved sequence motifs described above, a region that interacts with the coactivator Ada2, and a C-terminal bromodomain that is believed to interact with acetyl-lysine residues. Members of the GNAT family are important for the regulation of cell growth and development. In mice, knockouts of Gcn5L are embryonic lethal. Yeast Gcn5 is needed for normal progression through the G2-M boundary and mitotic gene expression. The importance of GNATs is probably related to their role in transcription and DNA repair.

The yeast GCN5 (yGCN5) transcriptional coactivator functions as a histone acetyltransferase (HAT) to promote transcriptional activation. The crystal structure of the yeast histone acetyltransferase Hat1-acetyl coenzyme A (AcCoA) shows that Hat1 has an elongated, curved structure, and the AcCoA molecule is bound in a cleft on the concave surface of the protein, marking the active site of the enzyme. A channel of variable width and depth that runs across the protein is probably the binding site for the histone substrate . The central protein core associated with AcCoA binding that appears to be structurally conserved among a superfamily of N-acetyltransferases, including yeast histone acetyltransferase 1 and Serratia marcescens aminoglycoside 3-N-acetyltransferase .

This entry represents the C-terminal region of histone acetyltransferase type B (

) (also known as HAT1) from fungi and metazoa, which is required for telomeric silencing and has intrinsic substrate specificity that modifies lysine in recognition sequence GXGKXG. It is also involved in DNA double-strand break repair. The structure from human HAT1 revealed that this domain consists of a bundle of helices with one short β-strand .
Endoribonuclease YicC-like, N-terminal (YicC-like_N)
Type: Domain

This entry represents the N-terminal region of Endoribonuclease YicC from Escherichia coli and similar bacterial sequences. YicC has been shown to be important for cells in the stationary phase, and essential for growth at high temperatures . This protein contributes to degradation of the small RNA (sRNA) RhyB by 3' to 5' exoribonuclease PNPase . It seems to generate a 3'-OH and a 5'-phosphate group.

This entry also includes the Endoribonuclease YloC from Bacillus subtilis that cleaves ssRNA, preferentially at U residues, generating a 3'-OH and a 5'-phosphate group, with no activity on dsRNA or dsDNA . YloC was found to act similarly to YicC in an Escherichia coli in vivo assay that assesses decay of the small RNA, RyhB .