SII-SWORD/CoKE huggingface dataset:
Glyoxylate reductase GyaR (Glyoxylate_reductase_GyaR)
Type: Family

The GyaR family of glyoxylate reductases catalyses the NADH-linked reduction of glyoxylate to glycolate. This family is found in hyperthermophilic archaea, where it is thought to play an important role in the glyoxylate and 3-hydroxypropionic acid cycles . Structurally, GyaR is similar to other NADH-linked dehydrogenases . The enzyme's thermostability appears to be due to the presence of aromatic clusters and the fact that it has more ion pairs and a relatively lower hydrophobic accessible surface area than mesophilic enzymes.
UV-endonuclease UvdE, bacterial (UvdE_bac)
Type: Family

Proteins in this entry are bacterial UV DNA damage endonucleases. They help the removal of UV-light damaged nucleotides. They can recognise pyrimidine dimers and cleave a phosphodiester bond immediately 5' to the lesion .
Translation release factor pelota, archaea (Pelota_arc)
Type: Family

Proteins in this entry are archaeal homologues of the eukaryotic gene pelota (DOM34 in yeast), which functions in recognising stalled ribosomes .
Chromosome-anchoring protein RacA (Chrosome_anchoring_RacA)
Type: Family

Spore formation in Bacillus subtilis involves a highly asymmetric cell division where the chromosome destined to enter the spore needs to move to the extreme pole of the cell in order to be captured in the prespore cell. This is accomplished by a specialised that moves the oriC region of the chromosome close to the cell pole before septation. RacA, a DNA-binding protein, is part of this system and is required for proper chromosome separation . It binds in a dispersed manner throughout the chromosome but preferentially to sites clustered in the origin portion of the chromosome, causing condensation of the chromosome and its remodelling into an elongated, anchored structure.
Histidine decarboxylase, bacteria (Hist_deCOase_bac)
Type: Family

Pyridoxal phosphate is the active form of vitamin B6 (pyridoxine or pyridoxal). Pyridoxal 5'-phosphate (PLP) is a versatile catalyst, acting as a coenzyme in a multitude of reactions, including decarboxylation, deamination and transamination . PLP-dependent enzymes are primarily involved in the biosynthesis of amino acids and amino acid-derived metabolites, but they are also found in the biosynthetic pathways of amino sugars and in the synthesis or catabolism of neurotransmitters; pyridoxal phosphate can also inhibit DNA polymerases and several steroid receptors . Inadequate levels of pyridoxal phosphate in the brain can cause neurological dysfunction, particularly epilepsy .

PLP enzymes exist in their resting state as a Schiff base, the aldehyde group of PLP forming a linkage with the ε-amino group of an active site lysine residue on the enzyme. The α-amino group of the substrate displaces the lysine ε-amino group, in the process forming a new aldimine with the substrate. This aldimine is the common central intermediate for all PLP-catalysed reactions, enzymatic and non-enzymatic .

A number of pyridoxal-dependent decarboxylases share regions of sequence similarity, particularly in the vicinity of a conserved lysine residue, which provides the attachment site for the pyridoxal-phosphate (PLP) group . Among these enzymes are aromatic-L-amino-acid decarboxylase (L-dopa decarboxylase or tryptophan decarboxylase), which catalyses the decarboxylation of tryptophan to tryptamine ; tyrosine decarboxylase, which converts tyrosine into tyramine; histidine decarboxylase, which catalyses the decarboxylation of histidine to histamine ; L-aspartate decarboxylase, which converts aspartate to beta-alanine ; and phenylacetaldehyde synthase that catalyses the decarboxylation of L-phenylalanine to 2-phenylethylamine . These enzymes belong to the group II decarboxylases .

This entry represents histidine decarboxylases from bacteria. These decarboxylases belong to the group II decarboxylase family, and convert L-histidine to histamine and CO
2
.
Uncharacterised protein family SprT-like (Uncharacterised_SprT-like)
Type: Family

The proteins in this entry have no known function.
Ureidoglycolate lyase, bacterial (Ureidogly_lyase_bac)
Type: Family

Ureidoglycolate lyase (

) is involved in the degradation of ureidoglycolate, an intermediate of purine degradation. It breaks down (S)-ureidoglycolate to produce glyoxylate and urea . This family of ureidoglycolate lyases were initially annotated as ureidoglycolate hydrolases, but this has since been corrected .

This entry represents bacterial ureidoglycolate lyase.
Sulphur relay, TusB (Sulphur_relay_TusB)
Type: Family

This entry represents TusB, which is a part of a sulphur-relay system required for 2-thiolation of 5-methylaminomethyl-2-thiouridine (mnm(5)s(2)U) at tRNA wobble positions . TusB is part of a heterohexamer, formed by a dimer of trimers; the hexameric TusBCD complex contains 2 copies each of TusB, TusC and TusD. The TusBCD complex interacts with TusE .
Adaptive-response sensory-kinase SasA (Kinase_SasA)
Type: Family

This entry represents the adaptive-response sensory-kinase SasA family, a member of the two-component regulatory system SasA/RpaA involved in genome-wide circadian gene expression . This family of proteins participate in the kaiABC clock protein complex, which constitutes the main circadian regulator in cyanobacteria, via its interaction with kaiC . It is required for robustness of the circadian rhythm of gene expression and involved in clock output . The kaiABC complex has a core comprising a kaiC homohexamer, a kaiB dimer and two kaiA dimers. KaiC enhances the autophosphorylation activity of SasA, which then transfers its phosphate group to RpaA to activate it. Proteins in this entry contain a histidine kinase domain.
Major facilitator superfamily transporter, TsgA (MFS_TsgA)
Type: Family

The proteins in this entry have no known function but are multi-pass membrane proteins that are putative transporters, which are induced by tellurite and selenite.
RNA chaperone ProQ (ProQ)
Type: Family

ProQ is a RNA chaperone with significant RNA binding, RNA strand exchange and RNA duplexing activities. It may regulate ProP activity through an RNA-based, post-transcriptional mechanism. It contains a FinO-like domain that serves as a high-affinity RNA-binding domain and a Hfq-like domain that is largely responsible for RNA strand exchange and duplexing .
Cytochrome b6, PetB (Cyt_B6_PetB)
Type: Family

In the mitochondrion of eukaryotes and in aerobic prokaryotes, cytochrome b is a component of respiratory chain complex III (

) - also known as the bc1 complex or ubiquinol-cytochrome c reductase. In plant chloroplasts and cyanobacteria, there is a analogous protein, cytochrome b6, a component of the plastoquinone-plastocyanin reductase (

), also known as the b6f complex. Both of these complexes are involved in electron transport and the generation of ATP and are therefore vitally important to the cell.

Cytochrome b/b6 is an integral membrane protein of approximately 400 amino acid residues that probably has 8 transmembrane segments. In plants and cyanobacteria, cytochrome b6 consists of two subunits encoded by the petB and petD genes. The sequence of petB is colinear with the N-terminal part of mitochondrial cytochrome b, while petD corresponds to the C-terminal part. Cytochrome b/b6 non-covalently binds two haem groups, known as b562 and b566. Four conserved histidine residues are postulated to be the ligands of the iron atoms of these two haem groups.

Apart from regions around some of the histidine haem ligands, there are a few conserved regions in the sequence of b/b6. The best conserved of these regions includes an invariant P-E-W triplet which lies in the loop that separates the fifth and sixth transmembrane segments. It seems to be important for electron transfer at the ubiquinone redox site - called Qz or Qo (where o stands for outside) - located on the outer side of the membrane. This entry is the N terminus of these proteins.

Proteins in this entry belong to the PetB family of cytochrome b6.
Preprotein translocase subunit SecG (Preprot_translocase_SecG)
Type: Family

SecG is an homologue of Sec61 subunit beta, a component of the Sec61/SecYEG protein secretory system. It is involved in protein export. The function of this subunit is unknown, but it may be involved in stabilisation of the trimeric complex.
H/ACA ribonucleoprotein complex subunit Nop10 , archaeal-type (Nop10_arc-typ)
Type: Family

Nop10 is a component of the small nucleolar ribonucleoprotein particles containing H/ACA-type snoRNAs (H/ACA snoRNPs). H/ACA snoRNPs are primarily responsible for catalysing the isomerisation of uridine to pseudouridine (Psi) in ribosomal and other cellular RNAs. The protein component of the H/ACA snoRNP consists of Cbf5, Gar1, Nhp2 and Nop10. The complex contains a stable core composed of Cbf5 and Nop10, to which Gar1 and Nhp2 subsequently bind. Nop10 has an essential role in the assembly and activity of these particles and binds directly to the Cbf5 to form the minimal active enzyme in archaea. The complex interacts with snoRNAs, Nop10 acting as a molecular adaptor for guiding snoRNP assembly .
Ribosomal protein bS6-L-glutamate ligase (RimK)
Type: Family

Escherichia coli
RimK (also known as Ribosomal protein bS6-L-glutamate ligase) adds additional Glu residues to the native Glu-Glu C terminus of ribosomal protein bS6. Mutation of the Glu-Glu terminus to Lys-Glu blocked addition. Ribosomal protein bS6 has the C-terminal sequence Glu-Glu in few species, suggesting the homologue of RimK may have a function other than bS6 modification in those species. However, most species having a member of this protein subfamily do not have an bS6 homologue ending in Glu-Glu. .
Rof/RNase P-like (Rof/RNase_P-like)
Type: Homologous_superfamily

This superfamily represents a domain with a core β barrel found in the inhibitor of Rho (Rof) and in ribonuclease P .
Threonylcarbamoyl-AMP synthase (TC-AMP_synthase)
Type: Family

This entry represents the threonylcarbamoyl-AMP synthase, includding RimN or YrdC (also known as TsaC) , which is involved in the biosynthesis of N6-threonyl-carbamoyl-adenosine (t6A) modified tRNA. This is a universal modification, found at position 37 of ANN decoding tRNAs. Analysis shows that YrdC binds ATP and preferentially binds tRNA-Thr lacking the t6A modification . Furthermore YrdC has been shown to have threonine-dependent ATPase activity that generates AMP . YrdC (TsaC) and proteins YgjD (TsaD), YjeE (TsaE), and YeaZ (TsaB), are necessary and sufficient for t6A biosynthesis in vitro, and may constitute a complex.
Coenzyme A disulphide reductase, staphyolococci (CoA_disulphide_reductase_staph)
Type: Family

Coenzyme A disulphide reductase (

) has been characterised in Staphylococcus aureus, Pyrococcus horikoshii, and Borrelia burgdorferi (Lyme disease spirochete), and inferred in several other species on the basis of high levels of CoA and an absence of glutathione as a protective thiol. Coenzyme A disulphide reductase specifically catalyses the NAD(P)H-dependent reduction of coenzyme A disulphide using FAD and NAD(P)H . In some species the enzymes show a distinct preference for NADH or NADPH, while others can use either substrate equally well. The reduction of disulphides occurs by a thiol-disulphide exchange reaction, but involves only a single catalytic cysteine residue that forms a stable mixed disulphide with CoA during catalysis. This enzyme contains 2 FAD binding domains and a single NAD(P)H binding domain .

This entry represents a distinct subgroup of coenzyme A disulphide reductases, so far found only in Staphylococcus species. These enzymes are specific for NADPH .
Deoxyuridine triphosphate nucleotidohydrolase, archaeal (dUTPase_archaeal)
Type: Family

The essential enzyme deoxyuridine triphosphate nucleotidohydrolase (dUTPase) (

) is specific for dUTP and is critical for the fidelity of DNA replication and repair. dUTPase hydrolyzes dUTP to dUMP and pyrophosphate, simultaneously reducing dUTP levels and providing the dUMP for dTTP biosynthesis. dUTPase decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA .

This entry represents archaeal dUTPases.
Ribonuclease P protein subunit RNP1 (RNP1)
Type: Family

Ribonuclease P (Rnp) is a ubiquitous ribozyme that catalyzes a Mg2 -dependent hydrolysis to remove the 5'-leader sequence of precursor tRNA (pre-tRNA) in all three domains of life . In bacteria, the catalytic RNA (typically ~120kDa) is aided by a small protein cofactor (~14kDa) . Archaeal and eukaryote RNase P consist of a single RNA and archaeal RNase P has four or five proteins, while eukaryotic RNase P consists of 9 or 10 proteins. Eukaryotic and archaeal RNase P RNAs cooperatively function with protein subunits in catalysis .

This entry represents RNP1 from archaea and its homologues from eukaryotes .
Ribonuclease P, protein component 3, archaeal (RNase_P_comp-3_arc)
Type: Family

This entry represents the protein component 3 of ribonuclease P. RNase P is a protein complex that functions in the processing of pre-tRNA, generating mature tRNA molecules by cleaving their 5'-ends. It consists of a RNA moiety and at least 4 protein subunits. Unlike most other natural ribozymes, it recognises and cleaves its substrate in trans .
Phosphopantetheine adenylyltransferase, archaea (PPAT_arch)
Type: Family

This entry contains phosphopantetheine adenyltransferases, primarily of the archaeal type. They are responsible for the ATP-dependent conversion of pantetheine 4'-phosphate to 3'-dephospho-CoA .
rRNA small subunit methyltransferase B, enterobacteriaceae (rRNA_ssu_MeTfrase_B_ent)
Type: Family

RNA (C5-cytosine) methyltransferases (RCMTs) catalyse the transfer of a methyl group to the 5th carbon of a cytosine base in RNA sequences to produce C5-methylcytosine. RCMTs use the cofactor S-adenosyl-L-methionine (SAM) as a methyl donor . The catalytic mechanism of RCMTs involves an attack by the thiolate of a Cys residue on position 6 of the target cytosine base to form a covalent link, thereby activating C5 for methyl-group transfer. Following the addition of the methyl group, a second Cys residue acts as a general base in the beta-elimination of the proton from the methylated cytosine ring. The free enzyme is restored and the methylated product is released .

Numerous putative RCMTs have been identified in archaea, bacteria and eukaryota ; most are predicted to be nuclear or nucleolar proteins . The Escherichia coli Ribosomal RNA Small-subunit Methyltransferase Beta (RSMB) FMU (FirMicUtes) represents the first protein identified and characterised as a cytosine-specific RNA methyltransferase. RSMB was reported to catalyse the formation of C5-methylcytosine at position 967 of 16S rRNA .

A classification of RCMTs has been proposed on the basis of sequence similarity . According to this classification, RCMTs are divided into 8 distinct subfamilies . Recently, a new RCMT subfamily, termed RCMT9, was identified . Members of the RCMT contain a core domain, responsible for the cytosine-specific RNA methyltransferase activity. This 'catalytic' domain adopts the Rossman fold for the accommodation of the cofactor SAM . The RCMT subfamilies are also distinguished by N-terminal and C-terminal extensions, variable both in size and sequence .

The rRNA small subunit methyltransferase B (RsmB) protein, often referred to as Fmu, has been demonstrated to methylate only C967 of the 16S ribosomal RNA and to produce only m5C at that position . The structure of the E. coli protein has been determined . It contains three subdomains which share structural homology to DNA m5C methyltransferases and two RNA binding protein families. The N-terminal sequence shares homology to another (noncatalytic) RNA binding protein, e.g. the ribosomal RNA antiterminator protein NusB (

). The catalytic lobe of the N1 domain, comprises the conserved core identified in all of the putative RNA m5C MTase sequences. Although the N1 domain is structurally homologous to known RNA binding proteins, there is no clear sequence motif that defines its role in RNA binding and recognition. At the functional centre of the catalytic lobe is the MTase domain of Fmu (residues 232-429), which adopts a fold typical of known AdoMet-dependent methyltransferases. In spite of the lack of a conserved RNA binding motif in the N1 domain, the close association of the N1 and MTase domains suggest that any RNA bound in the active site of the MTase domain is likely to interact with the N1 domain.

Theis entry is specific for the enterobacterial RsmB proteins.
Ribosomal RNA large subunit methyltransferase I (RLMI)
Type: Family

Members of this entry specifically methylate the cytosine at position 1962(m5C1962) of 23S rRNA .
rRNA small subunit methyltransferase C (rRNA_ssu_MeTfrase_C)
Type: Family

Members of this entry specifically methylate the guanosine at position 1207 of 16S rRNA .
ABC transporter, vitamin B12-binding protein (ABC_transptr_vit_B12-bd)
Type: Family

This entry represents Vitamin B12-binding protein Escherichia coli (BtuF) and similar found in gammaproteobacteria.

The vitamin B12-binding protein BtuF is part of the ABC transporter complex BtuCDF involved in vitamin B12 import. This protein binds vitamin B12 and delivers it to the periplasmic surface of BtuC .

The ATP-Binding Cassette (ABC) superfamily forms one of the largest of all protein families with a diversity of physiological functions . Several studies have shown that there is a correlation between the functional characterisation and the phylogenetic classification of the ABC cassette . More than 50 subfamilies have been described based on a phylogenetic and functional classification ; (for further information see http://www.tcdb.org/tcdb/index.php?tc=3.A.1).
rRNA small subunit methyltransferase F (rRNA_ssu_MeTfrase_F)
Type: Family

Members of this entry specifically methylate the cytosine at position 1407(m5C1407) of 16S rRNA .
Methylated-DNA--protein-cysteine methyltransferase (MGMT)
Type: Family

The repair of DNA containing O6-alkylated guanine is carried out by DNA-[protein]-cysteine S-methyltransferase (

), also known as 6-O-methylguanine-DNA methyltransferase. The major mutagenic and carcinogenic effect of methylating agents in DNA is the formation of O6-alkylguanine. The alkyl group at the O-6 position is transferred to a cysteine residue in the enzyme . This is a suicide reaction since the enzyme is irreversibly inactivated and the methylated protein accumulates as a dead-end product .
Digeranylgeranylglyceryl phosphate synthase (DGGGP_synth)
Type: Family

Digeranylgeranylglyceryl phosphate (DGGGP) synthase is a prenyltransferase involved in the synthesis of archaeal membrane ether-linked lipids . This enzyme catalyses the transfer of a geranylgeranyl group from geranylgeranyl diphosphate to (geranylgeranylglyceryl phosphate. DGGGP synthase has been found in almost all sequenced archaeal genomes, indicating its importance in membrane biosynthesis.
Probable Brix domain-containing ribosomal biogenesis protein (Brix_dom_Rbsml_bgen_prot)
Type: Family

This entry represents archaeal sequences containing a single Brix domain. The sequences have two unique characteristics: (1) the Brix domain charged regions are totally absent at the N terminus and are reduced in number to about 10 residues at the C terminus; and (2) the C-terminal part of the Brix domain itself is minimal. Biological data for some proteins in this family suggest a role in ribosome biogenesis and rRNA binding .
Subtilisin inhibitor (Subtilisin_inhibitor)
Type: Domain

The Streptomyces family of bacteria produce a number of proteinase inhibitors, which belong to MEROPS inhibitor family I16, clan IY. They are characterised by their strong activity towards subtilisin (MEROPS peptidase family S8,

) and are collectively known as Streptomyces subtilisin inhibitors (SSI). Some SSI also inhibit trypsin, chymotrypsin (MEROPS peptidase family S1,

) and griselysin (MEROPS peptidase family M4,

) . Mutation of the active site residue can influence inhibition specificity .

SSI is a homodimer, each monomer containing 2 anti-parallel β-sheets and 2 short α-helices. Protease binding induces the widening of a channel-like structure, in which hydrophobic side-chains are sandwiched between 2 lobes . Loss of the C-terminal tetrapeptide VFAF drastically reduces the inhibitory effect of the proteins when there is less than one molecule of inhibitor present per molecule of enzyme. This implies that the tetrapeptide is neccessary to maintain the correct 3D fold . Structural similarities between the primary and secondary contact loops of SSI, and the ovomucoid and pancreatic secretory trypsin inhibitor family suggest evolution of the 2 families from a common ancestor .
PKHD-type hydroxylase (PKHD_hydroxylase)
Type: Family

This entry contains bacterial PKHD-type hydroxylases.
Iron-sulfur cluster repair protein ScdA (ScdA)
Type: Family

The ScdA protein was originally identified as a cell wall biosynthesis protein since mutations in the scdA gene produce cell walls with highly aberrant morphology . Subsequent studies have shown that ScdA belongs to the wider Repairs of iron centres (RIC) family and is a di-iron protein that, amongst other functions, protects the cell from damage caused by exposure to nitric oxide and to hydrogen peroxide .
Hut operon regulatory protein HutP, bacillales (Regulatory_HutP_bacillales)
Type: Family

The HutP protein regulates the expression of Bacillus 'hut' structural genes by an anti-termination complex, which recognises three UAG triplet units, separated by four non-conserved nucleotides on the RNA terminator region. L-Histidine and Mg2+ ions are also required. These proteins exhibit the structural elements of alpha/beta proteins, arranged in the order: α-α-β-α-α-β-β-β in the primary structure, and the four antiparallel β-strands form a β-sheet in the order beta1-beta2-beta3-beta4, with two α-helices each on the front (alpha1 and alpha2) and at the back (alpha3 and alpha4) of the β-sheet .
Uncharacterised methyltransferase, YrrT (Uncharacterised_MeTfrase_YrrT)
Type: Family

This entry represent uncharacterised methyltransferases that belong to the YrrT family. It has been suggested that they are S-adenosyl-L-methionine-dependent.
ATP-dependent RNA helicase RhlB type (RNA_helicase_ATP-dep_RhlB)
Type: Family

This entry represents the RhiB type of ATP-dependent RNA helicases. They contain a DEAD box domain. They are responsible for ATP-dependent unwinding of double-stranded RNA as part of the RNA degradosome .
Thiol-disulphide oxidoreductase ResA (Thiol-dS_OxRdtase_ResA)
Type: Family

The thiol-disulphide oxidoreductase protein ResA acts in cytochrome c maturation by reducing the disulphide bond present in apocytochromes prior to covalent attachment of heme .
4-deoxy-4-formamido-L-arabinose-phosphoundecaprenol deformylase ArnD, probable (ArnD)
Type: Family

This entry represents probable 4-deoxy-4-formamido-L-arabinose-phosphoundecaprenol deformylases ArnD .
Tryptophan RNA-binding attenuator protein domain (Trp_RNA-bd_attenuator_dom)
Type: Domain

The tryptophan RNA-binding attenuation protein (TRAP) regulates expression of the tryptophan biosynthetic genes in Bacillus sp. by binding to the leader region of the nascent trp operon mRNA . The crystal structure of the Trp RNA-binding attenuation protein of Bacillus subtilis (mtrB,

) has been solved . TRAP forms an oligomeric ring consisting of 11 single-domain subunits, where each subunit adopts a double-stranded β-helix structure with the appearance of a β-sandwich of distinct architecture and jelly-roll fold. The 11 subunits are stabilised by 11 inter-subunit strands, forming a β-wheel with a large central hole. TRAP is activated by binding to tryptophan in clefts between adjacent β-strands, which induces conformational changes in the protein. Activated TRAP binds an mRNA target sequence consisting of 11 (G/U)AG repeats, separated by 2-3 spacer nucleotides. The spacer nucleotides do not make direct contact with the TRAP protein, but they do influence the conformation of the RNA, which might influence the specificity of TRAP .

This entry represents the structural domain in the TRAP family of proteins.