SII-SWORD/CoKE huggingface dataset:
DnaA regulatory inactivator Hda, Enterobacteriaceae (Hda_Enterobact)
Type: Family

This entry represents the Hda (Homologous to DnaA) proteins, which are about half the length of DnaA and homologous over the entire length of Hda. In Escherichia coli, the initiation of DNA replication requires DnaA bound to ATP rather than ADP; Hda helps facilitate the conversion of DnaA-ATP to DnaA-ADP, thus inhibiting the inititation of DNA replication .

This entry represents Hda proteins from Enterobacteriaceae.
DNA ligase, ATP-dependent, bacterial/archaeal (DNA_ligae_ATP-dep_bac/arc)
Type: Family

This entry represents bacterial and archaeal ATP-dependent DNA ligases.

DNA ligase (polydeoxyribonucleotide synthase) is the enzyme that joins two DNA fragments by catalysing the formation of an internucleotide ester bond between phosphate and deoxyribose. It is active during DNA replication, DNA repair and DNA recombination. There are two forms of DNA ligase, one requires ATP (

), the other NAD (

), the latter being restricted to eubacteria. Eukaryotic, archaebacterial, viral and some eubacterial DNA ligases are ATP-dependent. The first step in the ligation reaction is the formation of a covalent enzyme-AMP complex. The co-factor ATP is cleaved to pyrophosphate and AMP, with the AMP being covalently joined to a highly conserved lysine residue in the active site of the ligase. The activated AMP residue is then transferred to the 5'phosphate of the nick, before the nick is sealed by phosphodiester-bond formation and AMP elimination .
Heat shock protein HspQ (HspQ)
Type: Family

This entry represents the bacterial heat shock protein HspQ family. They are involved in the degradation of certain denaturated proteins, including DnaA, during heat shock stress.

The crystal structure of HspQ from Escherichia coli showed a trimeric structure stabilized by a large and hydrophobic interaction surface .
Protein-methionine-sulfoxide reductase subunit MsrP (MsrP)
Type: Family

MsrPQ is an enzymatic system that repairs proteins containing methionine sulfoxide in the bacterial cell envelope. MsrP, a molybdo-enzyme, and MsrQ, a haem-binding membrane protein, are widely conserved throughout Gram-negative bacteria. MsrPQ uses electrons from the respiratory chain, which represents a novel mechanism to import reducing equivalents into the bacterial cell envelope. MsrPQ is essential for the maintenance of envelope integrity under bleach stress, rescuing periplasmic proteins from methionine oxidation, including the primary periplasmic chaperone SurA .

MsrP have been shown to be able to reduce protein-bound methionine sulfoxide and be able to repair a wide range of periplasmic proteins in vitro .
Phycocyanobilin:ferredoxin oxidoreductase (Ferredoxin_bilin_OxRdtase)
Type: Family

This entry represents phycocyanobilin:ferredoxin oxidoreductases. They are involved in the reduction of biliverdin IX-alpha.
Para-hydroxybenzoic acid efflux pump, subunit AaeA (PHBA_efflux_pump_AaeA)
Type: Family

This entry represents the p-hydroxybenzoic acid efflux pump subunit AaeA.
Quinate/Shikimate dehydrogenase (Quinate/Shikimate_DH)
Type: Family

This entry represents a group of bifunctional enzymes

, quinate/shikimate dehydrogenase . This is the second shikimate dehydrogenase enzyme found in Escherichia coli and differs from

(

), in that it can use both quinate and shikimate as substrate and either NAD(+) or NADP(+) as acceptor.
Valine-tRNA ligase, type 2 (Valine-tRNA_ligase_type_2)
Type: Family

This entry represents the type 2 subfamily of the valine-tRNA ligases.

Valine-tRNA ligase (also known as Valyl-tRNA synthetase) (

) is an alpha monomer that belongs to class Ia aminoacyl-tRNA ligase.

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .
Redox-sensing transcriptional repressor Rex (Tscrpt_rep_Rex)
Type: Family

This entry represents the redox-sensing transcriptional repressor Rex. Rex is thought to be responsible for modulating transcription according to changes in the cellular NADH/NAD(+) redox state.
Protein of unknown funcion UPF0173 (UPF0173)
Type: Family

This entry represents a group of uncharacterised proteins that belong to the UPF0173 family of metal-dependent hydrolases predominantly found in bacteria and archaea.
V-type ATP synthase catalytic alpha chain (V-ATPase_asu)
Type: Family

This entry represents the catalytic subunit alpha of V-type ATP synthase, which is known as subunit A in eukaryotes. In bacteria and archaea it produces ATP from ADP in the presence of a proton gradient across the membrane.

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

A-type ATPases (archaeal-type ATPases) and V-ATPases, all included in this entry, are thought to have evolved from common ancestral genes .
V-type ATP synthase regulatory subunit B/beta (V-ATPase_su_B/beta)
Type: Family

This entry represents the beta regulatory subunit of V-type ATP synthase, known as subunit B in eukaryota.

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

A-type ATPases (archaeal-type ATPases) and V-ATPases, all included in this entry, are thought to have evolved from common ancestral genes .
DNA polymerase IV (DNApol_IV)
Type: Family

DNA polymerase IV is a poorly processive, error-prone DNA polymerase involved in untargeted mutagenesis. It copies undamaged DNA at stalled replication forks, which arise in vivo from mismatched or misaligned primer ends. These misaligned primers can be extended by polIV. It exhibits no 3'-5' exonuclease (proofreading) activity and may be involved in translesional synthesis .
Ribosomal RNA large subunit methyltransferase, Cfr (rRNA_lsu_MeTfrase_Cfr)
Type: Family

This entry represents the Cfr subfamily of RlmN methyltransferases.

Ribosomal RNA large subunit methyltransferase Cfr specifically methylates position 8 of adenine 2503 in 23S rRNA. It can also methylate position 2 of A2503 after the primary methylation is complete, to form 2,8-dimethyladenosine. Cfr confers antibiotic resistance in bacteria. The antibiotic resistance is provided by methylation at the 8 position and is independent of methylation at the 2 position of A2503 .
tRNA1(Val) (adenine(37)-N6)-methyltransferase (tRNA_adenine-N6_MeTrfase)
Type: Family

Proteins in this family specifically methylate the adenine in position 37 of tRNA (Val) .
4-amino-4-deoxy-L-arabinose-phosphoundecaprenol flippase, subunit ArnE (Flippase_ArnE)
Type: Family

This entry represents ArnE, which is an integral membrane component of the ArnE/ArnF (heterodimer) undecaprenyl-phosphate-alpha-L-Ara4N flippase. The ArnE/ArnF undecaprenyl-phosphate-alpha-L-Ara4N flippase is responsible for transporting undecaprenyl-phosphate-alpha-L-Ara4N from the cytoplasmic face of the inner membrane to the periplasmic face of the inner membrane.

ArnE and ArnF are both predicted to be integral membrane proteins with 4 transmembrane helices and belong to the drug/metabolite transporter (DMT) superfamily .

Deletion of arnE or arnF results in restoration of polymyxin sensitivity in a polymyxin-resitant pmrAc strain and are defective for transfer of undecaprenyl-phosphate-alpha-L-Ara4N from the cytoplasmic face of the inner membrane to the periplasmic face and for attachment of L-Ara4N to lipid A. Both ArnE and ArnF are required for polymyxin resistance as expression from a plasmid of one cannot replace a deletion of the other .
NAD(P)H-quinone oxidoreductase subunit D/H (NDH1_su_D/H)
Type: Family

NAD(P)H-quinone oxidoreductase or NAD(P)H dehydrogenase 1 subunit D shuttles electrons from NADH, via FMN and iron-sulphur (Fe-S) centres, to quinones in the respiratory chain. The immediate electron acceptor for the enzyme in this species is believed to be ubiquinone. It couples the redox reaction to proton translocation (for every two electrons transferred, four hydrogen ions are translocated across the cytoplasmic membrane), and thus conserves the redox energy in a proton gradient.

This subunit is known as subunit H in chloroplasts and cyanobacteria. In chloroplasts NDH shuttles electrons from NAD(P)H:plastoquinone, via FMN and iron-sulphur (Fe-S) centres, to quinones in the photosynthetic chain and possibly in a chloroplast respiratory chain. The immediate electron acceptor for the enzyme in this species is believed to be plastoquinone. In cyanobacteria NDH-1 shuttles electrons from an unknown electron donor, via FMN and iron-sulphur (Fe-S) centres, to quinones in the respiratory and/or the photosynthetic chain.The immediate electron acceptor for the enzyme in this species is believed to be plastoquinone.

This subunit often appears as a fusion of subunits C and D.
Cell division suppressor protein, YneA (Cell_div_suppressor_YneA)
Type: Family

The YneA protein is responsible for cell division suppression during the SOS response in Bacillus subtilis. Localization of the FtsZ protein to the cell division site was reduced in dinR-disrupted or yneA-expressing cells, further suggesting that the YneA protein suppresses cell division through the suppression of FtsZ ring formation. Interestingly, the B. subtilis YneA protein is structurally and phylogenetically unrelated to its functional counterpart in Escherichia coli, SulA (see

).
DNA-binding protein, archaeal (DNA_bind_arc)
Type: Family

This entry represents DNA binding proteins from archaea belonging to the PDCD5 family.
Ferredoxin--NADP reductase, type 2 (Fd--NADP_Rdtase_type_2)
Type: Family

The function of ferredoxin--NADP reductase is to mediate the following reaction: 2 reduced ferredoxin + NADP(+) + H(+) = 2 oxidized ferredoxin + NADPH .

Although all ferredoxin-NADP+ reductases (FNRs) catalyze the same reaction, they belong to two unrelated families of proteins: the plant-type and the glutathione reductase-type of FNRs . This entry represents the second type.
Triosephosphate isomerase, archaeal (Triosephosphate_isomerase_arc)
Type: Family

Triosephosphate isomerase (

) (TIM) is the glycolytic enzyme that catalyses the reversible interconversion of glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. TIM plays an important role in several metabolic pathways and is essential for efficient energy production, highly conserved in prokaryotes and eukaryotes. In pathogenic organisms, this enzyme plays a crucial role obtaining energy for infection and survival. TIM is a dimer of identical subunits, each of which is made up of about 250 amino-acid residues. A glutamic acid residue is involved in the catalytic mechanism .

The tertiary structure of TIM has eight β/α motifs folded into a barrel structure. The TIM barrel fold occurs ubiquitously and is found in numerous other enzymes that can be involved in energy metabolism, macromolecule metabolism, or small molecule metabolism .

The sequence around the active site residue is perfectly conserved in all known TIM's. Deficiencies in TIM are associated with haemolytic anaemia coupled with a progressive, severe neurological disorder .

This entry represents archaeal triosephosphate isomerases.
Ribonuclease HI (RNaseHI)
Type: Family

Ribonuclease H (RNase H)

recognises and cleaves the RNA strand of RNA-DNA heteroduplexes. RNases H are classified into two types. Type 1 RNases H include prokaryotic and eukaryotic RNases H1 and retroviral RNase H. Type 2 RNases H include prokaryotic and eukaryotic RNases H2 and bacterial RNase H3 . In prokaryotes RNase H is involved in removing the RNA of RNA-DNA hybrids, particularly the primers of Okazaki fragments in lagging-strand DNA synthesis .

This family consists of bacterial RNases HI and viral RNases H.
Shikimate dehydrogenase family (Shikimate_DH_fam)
Type: Family

This entry represents shikimate dehydrogenase (

) and quinate/shikimate dehydrogenase (

). The latter is the second shikimate dehydrogenase enzyme found in Escherichia coli and differs from

(

), in that it can use both quinate and shikimate as substrate and either NAD(+) or NADP(+) as acceptor.
Oligoribonuclease (Oligoribonuclease)
Type: Family

Oligoribonuclease (Orn) is a DEDDh-type DnaQ-like 3'-5' exoribonuclease that is responsible for degrading small oligoribonucleotides to mononucleotides. It contains three conserved sequence motifs termed ExoI, ExoII and ExoIII, with a specific Hx(4)D conserved pattern at ExoIII. These motifs are clustered around the active site and contain four conserved acidic residues that serve as ligands for the two metal ions required for catalysis. Orn is essential for Escherichia coli survival . The human homologue, also called Sfn (small fragment nuclease), is able to hydrolyse short single-stranded RNA and DNA oligomers. It plays a role in cellular nucleotide recycling .
Flap endonuclease Xni (Xni)
Type: Family

This entry contains the bacterial flap endonuclease Xni (also known as YgdG), which was previously identified as a 3'-5' exonuclease and named exonuclease IX (ExoIX) . Xni was subsequently found to possess flap endonuclease activity, but not exonuclease activity .
Triosephosphate isomerase, bacterial/eukaryotic (TrioseP_Isoase_bac/euk)
Type: Family

Triosephosphate isomerase (

) (TIM) is the glycolytic enzyme that catalyses the reversible interconversion of glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. TIM plays an important role in several metabolic pathways and is essential for efficient energy production, highly conserved in prokaryotes and eukaryotes. In pathogenic organisms, this enzyme plays a crucial role obtaining energy for infection and survival. TIM is a dimer of identical subunits, each of which is made up of about 250 amino-acid residues. A glutamic acid residue is involved in the catalytic mechanism .

The tertiary structure of TIM has eight β/α motifs folded into a barrel structure. The TIM barrel fold occurs ubiquitously and is found in numerous other enzymes that can be involved in energy metabolism, macromolecule metabolism, or small molecule metabolism .

The sequence around the active site residue is perfectly conserved in all known TIM's. Deficiencies in TIM are associated with haemolytic anaemia coupled with a progressive, severe neurological disorder .

This entry represents bacterial and eukaryotic triosephosphate isomerases.
HTH-type transcription regulator MntR (HTH_tscrpt_reg_MntR)
Type: Family

This entry contains the Bacillus subtilis YqhN (MntR), which encodes a metalloregulatory protein distantly related to the Corynebacterium diphtheriae diphtheria toxin repressor (DtxR). While DtxR mediates the iron-dependent repression of iron uptake, MntR encodes a manganese modulated regulator of manganese transport. MntR is the central regulator of manganese homeostasis. In the presence of manganese, it mediates repression of the manganese transporter MntH and under low manganese conditions, it activates the transcription of the mntABCD operon .
Ribonuclease HII (RNase_HII)
Type: Family

Ribonuclease HII is involved in the degradation of the ribonucleotide moiety on RNA-DNA hybrid molecules carrying out endonucleolytic cleavage to 5'-phospo-monoester . This entry is specific for ribonuclease HII. Several bacteria, such as Bacillus subtilis, have two different type II RNases H, RNases HII and HIII ; double deletion of these leads to cellular lethality. It appears that type I and type II RNases H also have overlapping functions in cells, as over-expression of Escherichia coli RNase HII can complement an RNase HI deletion phenotype . In Leishmania mitochondria, of the four distinct RNase H genes (H1, HIIA, HIIB, HIIC), HIIC is essential for the survival of the parasite and thus can be a potential target for anti-leishmanial chemotherapy . Ribonuclease H (RNase H) is classified into two families, type I (prokaryotic RNase HI, eukaryotic RNase H1 and viral RNase H) and type II (prokaryotic RNase HII and HIII, and eukaryotic RNase H2). RNase H endonucleolytically hydrolyzes an RNA strand when it is annealed to a complementary DNA strand in the presence of divalent cations, in DNA replication and repair .
Deoxyhypusine synthase, putative, archaeal (Deoxyhypus_synthase_arc)
Type: Family

Eukaryotic initiation factor 5A (eIF-5A), now considered to be an elongation factor (see

), contains an unusual amino acid, hypusine [N epsilon-(4-aminobutyl-2-hydroxy)lysine]. The first step in the post-translational formation of hypusine is catalysed by the enzyme deoxyhypusine synthase (DS,

). The enzyme catalyses the following reaction:

Spermidine + [eIF-5A]-lysine = 1,3-diaminopropane + [eIF-5A]-deoxyhypusine

The modified version of eIF-5A, and DS, are required for eukaryotic cell proliferation . The structure is known for this enzyme in complex with its NAD
+
cofactor.

This entry represents probable deoxyhypusine synthases from archaea.
snRNP Sm-like, putative, archaea (snRNP_Sm-like_arc)
Type: Family

This entry represents a family of Sm-like ribonucleoproteins from archaea.
N-acetyltransferase Eis (NAcTrfase_Eis)
Type: Family

Eis (enhanced intracellular survival) from Mycobacterium has been identified as a secretory protein that is released into the host cell to modulate inflammatory responses . It is an acetyltransferase of the GCN5-related family of N-acetyltransferases that initiates suppression of host immune responses by acetylation of DUSP16/MKP-7 .

This family also includes other putative N-acetyltransferases from Actinobacteria as yet uncharacterised.
Glycine cleavage system T protein, bacteria (GcvT_bac)
Type: Family

This entry represents GcvT from bacteria .

The glycine cleavage multienzyme complex (GCV) catalyses the catabolism of glycine in eukaryotes. GcvT (aminomethyltransferase,

) is a folate-dependent enzyme that catalyses the release of ammonia and the transfer of the methylene carbon unit (C1 unit) to tetrahydrofolate (H4folate) from the aminomethyl intermediate attached to the lipoate cofactor of H-protein . GCV is found in bacteria and the mitochondria of eukaryotes. Mutations in the human GcvT gene are known to cause nonketotic hyperglycinemia .
DNA-directed RNA polymerase subunit Rpo11-like (Rpo11-like)
Type: Family

DNA-directed RNA polymerases, also known as DNA-dependent RNA polymerases, are responsible for the polymerisation of ribonucleotides into a sequence complementary to the template DNA. Eukaryotes have three different DNA-directed RNA polymerases (RNAPs), Pol I, II, and III, whereas Archaea and Bacteria have single enzymes.

RNAPs are multisubunit enzymes. Archaeal RNAP is closely related to eukaryotic RNAP II , which consists of 12 subunits. Archaeal RNAP has an additional subunit, Rpo13, with no orthologue in the eukaryotic enzyme .

This entry represents a family of small subunits of RNAP of about 13 to 16kDa that are found in all three types of eukaryotic polymerases and in archaeal polymerase which are highly conserved and includes the archaeal DNA-dependent RNA polymerase subunit Rpo11 (also known as subunit L) and the eukaryotic RPB11/RPC19 RNA polymerase subunits. The name Rpo11 is based on eukaryotic terminology . The structure has been solved in conjunction with the D subunit .
Uncharacterised protein family UPF0127 (UPF0127)
Type: Family

This family represents a group of archaeal proteins that are functionally uncharacterised.
VapC family (VapC_family)
Type: Family

This entry represents VapC family of proteins, which are toxic components of a toxin-antitoxin (TA) module. VapC family members are ribonucleases but are unable to degrade ds- or ss-DNA . Several bacterial VapC proteins have been shown to be tRNA (fMet)-specific endonucleases .
tRNA(Phe) 7-((3-amino-3-carboxypropyl)-4-demethylwyosine(37)-N(4))-methyltransferase (Taw3)
Type: Family

The presence of Wyosine derivatives, such as wybutosine (yW), at position 37 of tRNA(Phe) is characteristic of Eukaryotes and Archaea. Four of the five wybutosine biosynthetic enzymes from Eukaryotes have homologues in Archaea. Taw3 is the archaeal homologue of eukaryotic Tyw3, responsible for the methylation at N4 of 4-demethylwyosine (imG-14) .
Large ribosomal subunit protein uL10, archaea (Ribosomal_uL10_arc)
Type: Family

This entry represents the large ribosomal subunit protein uL10 found in archaea. 50S ribosomal protein uL10 forms the large subunit's ribosomal stalk, playing a central role in the interaction of the ribosome with elongation factors .

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .