SII-SWORD/CoKE huggingface dataset:
Phosphotyrosine protein phosphatase I (Ptyr_pPase)
Type: Domain

Protein tyrosine (pTyr) phosphorylation is a common post-translational modification which can create novel recognition motifs for protein interactions and cellular localisation, affect protein stability, and regulate enzyme activity. Consequently, maintaining an appropriate level of protein tyrosine phosphorylation is essential for many cellular functions. Tyrosine-specific protein phosphatases (PTPase;

) catalyse the removal of a phosphate group attached to a tyrosine residue, using a cysteinyl-phosphate enzyme intermediate. These enzymes are key regulatory components in signal transduction pathways (such as the MAP kinase pathway) and cell cycle control, and are important in the control of cell growth, proliferation, differentiation and transformation . The PTP superfamily can be divided into four subfamilies :

(1) pTyr-specific phosphatases

(2) dual specificity phosphatases (dTyr and dSer/dThr)

(3) Cdc25 phosphatases (dTyr and/or dThr)

(4) LMW (low molecular weight) phosphatases

Based on their cellular localisation, PTPases are also classified as:

Receptor-like, which are transmembrane receptors that contain PTPase domains

Non-receptor (intracellular) PTPases

All PTPases carry the highly conserved active site motif C(X)5R (PTP signature motif), employ a common catalytic mechanism, and share a similar core structure made of a central parallel β-sheet with flanking α-helices containing a β-loop-α-loop that encompasses the PTP signature motif . Functional diversity between PTPases is endowed by regulatory domains and subunits.

This entry represents the low molecular weight (LMW) protein-tyrosine phosphatases (or acid phosphatase), which act on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates . The structure of a LMW PTPase has been solved by X-ray crystallography and is found to form a single structural domain. It belongs to the α/β class, with 6 α-helices and 4 β-strands forming a 3-layer α-β-α sandwich architecture.
Transcription factor TFIIB, conserved site (TFIIB_CS)
Type: Conserved_site

In eukaryotes, transcription initiation by polymerase II is modulated by both general and specific transcription factors. The general factors (which include TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIG and TFIIH) operate through common promoter elements, such as the TATA box. Transcription factor IIB (TFIIB) is of central importance in transcription of class II genes. It associates with TFIID-TFIIA bound to DNA (the DA complex) to form a ternary TFIID-IIA-IBB (DAB) complex, which is recognised by RNA polymerase II . TFIIB comprises ~315-340 residues and contains an imperfect C-terminal repeat of a 75-residue domain that may contribute to the symmetry of the folded protein.
HTH-type transcriptional regulator Hpr (HTH_tscrpt_reg_Hpr)
Type: Family

The MarR-type HTH domain is a DNA-binding, winged helix-turn-helix (wHTH) domain of about 135 amino acids present in transcription regulators of the MarR/SlyA family, involved in the development of antibiotic resistance. The MarR family of transcription regulators is named after Escherichia coli MarR, a repressor of genes which activate the multiple antibiotic resistance and oxidative stress regulons, and after slyA from Salmonella typhimurium and E. coli, a transcription regulator that is required for virulence and survival in the macrophage environment. Regulators with the MarR-type HTH domain are present in bacteria and archaea and control a variety of biological functions, including resistance to multiple antibiotics, household disinfectants, organic solvents, oxidative stress agents and regulation of the virulence factor synthesis in pathogens of humans and plants. Many of the MarR-like regulators respond to aromatic compounds .

The crystal structures of MarR, MexR and SlyA have been determined and show a winged HTH DNA-binding core flanked by helices involved in dimerisation. The DNA-binding domains are ascribed to the superfamily of winged helix proteins, containing a three (four)-helix (H) bundle and a three-stranded antiparallel β-sheet (B) in the topology: H1-(H1')-H2-B1-H3-H4-B2-B3-H5-H6. Helices 3 and 4 comprise the helix-turn-helix motif and the β-sheet is called the wing. Helix 4 is termed the recognition helix, like in other HTHs where it binds the DNA major groove. The helices 1, 5 and 6 are involved in dimerisation, as most MarR-like transcription regulators form dimers .

The proteins in this entry are all of the hpr type found in bacteria and function as negative regulators of protease production and sporulation.
Haloalkane dehalogenase, subfamily 1 (Haloalkane_dehalogenase_1)
Type: Family

Haloalkane dehalogenases catalyse the hydrolytic cleavage of carbon-halogen bonds in halogenated aliphatic compounds, leading to the formation of the corresponding primary alcohols, halide ions and protons . These enzymes can be divided into two subfamilies which differ in the amino acids and the topology of their catalytic triads. Subfamily 1 seems to have a preference for short-chain haloalkanes as substrates, whereas subfamily 2 seems to prefer long-chains.

This entry represents the subfamily 1 haloalkane dehalogenases.
HTH-type transcriptional regulator ArgP, gammaproteobacteria (ArgP_gammaproteobact)
Type: Family

This entry represents HTH-type transcriptional regulator ArgP from Gammaproteobacteria.

ArgP (formally known as IciA) is a positive regulator of argK. It is a negative autoregulator in presence of arginine. It competes with DnaA for oriC iteron (13-mer) binding. It activates dnaA and nrd transcription. It has been demonstrated to be part of the pho regulon . ArgP mutants convey canavanine (an L-arginine structural homologue) sensitivity . ArgP also affects lysine biosynthesis in E. coli through regulating dapB Gene .
Acyl carrier protein phosphodiesterase, gammaproteobacteria (ACP_phosphodiesterase_gpbac)
Type: Family

This entry contains the Acyl carrier protein phosphodiesterase (AcpH, also called ACP hydrolyase) from Escherichia coli. Proteins in this entry are restricted to the gammaproteobacteria. AcpH converts holo-ACP to apo-ACP by hydrolytic cleavage of the phosphopantetheine prosthetic group from ACP .

A mutant E. coli strain having a total deletion of the acpH grows normally, showing that phosphodiesterase activity is not essential for growth, although it is required for turnover of the ACP prosthetic group in vivo. AcpH is found only in Gram-negative organisms suggesting that it plays a role in some aspect of lipid metabolism that is unique to these organisms. The most obvious of which is biosynthesis of lipid A. Because AcpH is a hydrolase, it could possibly be an editing enzyme that intercepts acyl-ACPs that would give an inappropriate lipid A structure if used as acyl donors .
L-ribulose-5-phosphate 3-epimerase, Enterobacteriaceae (L-Ru-5P_3-Epase_Enterobacteria)
Type: Family

Proteins in this entry are L-ribulose-5-phosphate 3-epimerases (UlaE) from Enterobacteriaceae. They are supsected to be involved in isomerisation of L-xylulose-5-phosphate to L-ribulose-5-phosphate. UlaE in E. coli contains a TIM barrel and forms dimers .

The ulaABCDEF operon encodes an L-ascorbate phosphotransferase transport system (UlaABC, formerly designated SgaTBA)responsible for the uptake and phosphorylation of L-ascorbate. The ulaDEF genes encode three enzymes that catalyze the anaerobic conversion of the phosphorylated, hydrolytic product of L-ascorbate, 3-keto-L-gulonate-6-phosphate, to D-xylulose-5-phosphate, which is subsequently metabolized by the pentose phosphate pathway. UlaD catalyzes a β-keto acid decarboxylation reaction to produce L-xylulose-5-phosphate, which undergoes successive epimerization reactions with UlaE (L-xylulose-5-phosphate 3-epimerase) and UlaF (L-ribulose-5-phosphate 4-epimerase), yielding D-xylulose-5-phosphate, an intermediate in the pentose phosphate pathway.
N-methyl-L-tryptophan oxidase MTOX (Me_Trp_Oxase_MTOX)
Type: Family

N-methyl-L-tryptophan oxidase catalyzes the oxidative demethylation of N-methyl-L-tryptophan .
Cytochrome c biogenesis protein Ccs1/CcsB/ResB (Cyt_c_bgen_Ccs1/CcsB/ResB)
Type: Family

The Css1/CcsB/ResB family of proteins are found in bacteria and chloroplasts. They are essential for the biogenesis of c-type cytochromes, apparently being required at the step of heme attachment .
Sugar efflux transporter, putative (Sugar_effux_transptr_put)
Type: Family

This family is involved in the efflux of sugars. The physiological role may be the reduction of the intracellular concentration of toxic sugars or sugar metabolites.
Deoxyhypusine synthase-like (Deoxyhypusine_synthase-like)
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.

The entry represents a number of deoxyhypusine synthase-like proteins found in bacteria. The function of these proteins is not known.
Acid shock protein (Acid_shock)
Type: Family

Acid shock protein is required for growth and/or survival in acidic conditions. It is needed for the adaptation process at pH 4.5 that enables cells to survive at extremely low pH (pH 2.0) . The proteins generally consist of a conserved N terminus followed by three disordered repeats.
Zinc transporter ZupT (Zn_transptr_ZupT)
Type: Family

This entry is represented by ZupT, which mediates zinc uptake and which may also transport other divalent cations .
L-ribulose-5-phosphate 4-epimerase UlaF (UlaF)
Type: Family

The ulaABCDEF operon encodes an L-ascorbate phosphotransferase transport system (UlaABC, formerly designated SgaTBA)responsible for the uptake and phosphorylation of L-ascorbate. The ulaDEF genes encode three enzymes that catalyze the anaerobic conversion of the phosphorylated, hydrolytic product of L-ascorbate, 3-keto-L-gulonate-6-phosphate, to D-xylulose-5-phosphate, which is subsequently metabolized by the pentose phosphate pathway. UlaD catalyzes a β-keto acid decarboxylation reaction to produce L-xylulose-5-phosphate, which undergoes successive epimerization reactions with UlaE (L-xylulose-5-phosphate 3-epimerase) and UlaF (L-ribulose-5-phosphate 4-epimerase), yielding D-xylulose-5-phosphate, an intermediate in the pentose phosphate pathway.

This entry represents the UlaF proteins.
Zinc transporter ZitB (Zn_transptr_ZitB)
Type: Family

This entry is represented by ZitB, which is involved in zinc efflux across the cytoplasmic membrane, thus reducing zinc accumulation in the cytoplasm and rendering bacteria more resistant to zinc. It may contribute to zinc homeostasis at low concentrations of zinc, whereas ZntA is required for growth at more toxic concentrations . ZitB is potentially capable of transporting not only zinc but also cadmium, nickel and copper .
Proteasome-activating nucleotidase PAN (Nucleotidase_PAN)
Type: Family

Archaea mediate a form of post-translational modification of proteins termed sampylation that resembles ubiquitinylation. Proteasome-activating nucleotidase PAN1 from Haloferax volcanii has been shown to associate to sampylated proteins in proteasome-mediated proteolysis .

AAA-ATPase PAN is responsible for recognizing, binding, unfolding and translocation of substrate proteins into the archaeal 20S proteasome core particle. It is essential for opening the gate of the 20S proteasome via an interaction with its C terminus, thereby allowing substrate entry and access to the site of proteolysis. Thus, the C termini of the proteasomal ATPase function like a 'key in a lock' to induce gate opening and therefore regulate proteolysis. The unfolding activity requires energy from ATP hydrolysis, whereas ATP binding alone promotes ATPase-20S proteasome association which triggers gate opening, and supports translocation of unfolded substrates. In addition to ATP, it is able to cleave other nucleotide triphosphates such as CTP, GTP and UTP, but hydrolysis of these other nucleotides is less effective in promoting proteolysis than ATP. Moreover, PAN by itself can function as a chaperone in vitro .
G/U mismatch-specific DNA glycosylase MUG, bacterial (MUG_bact)
Type: Family

This family represents the bacterial G/U mismatch-specific DNA glycosylase MUG.

G:U mismatches resulting from deamination of cytosine are the most common pro-mutagenic lesions occurring in DNA. Uracil is removed in a base-excision repair pathway by uracil DNA-glycosylase (UDG), which excises uracil from both single- and double-stranded DNA. The uracil DNA glycosylase family 2 consists of thymine DNA glycosylase (TDG) from eukaryotes and mismatch-specific uracil DNA glycosylase (MUG) from prokaryotes.

Thymine DNA glycosylases (TDG) in eukaryotic organisms are known for their double-stranded glycosylase activity on guanine/uracil (G/U) base pairs . In human TDG removes uracil and thymine from G:U and G:T mismatches in double-stranded DNA . In E. coli MUG is highly specific to G:U mismatches but also repairs G:T mismatches at high enzyme concentration. Structural studies of E. coli MUG reveal its structural homology to UDG despite low sequence identity. It has a specific uracil-binding pocket located in a DNA-binding groove and this specificity is likely the result of a multistep lesion recognition process .
Ribosome biogenesis methyltransferase NEP1, archaea (Ribosome_NEP1_arc)
Type: Family

NEP1 (nucleolar essential protein 1), also named EMG1 (essential for mitotic growth 1), is involved in ribosomal biogenesis. It seems to play a role in a methylation reaction in pre-rRNA processing .
Bacteriohemerythrin-like protein (Bacteriohemerythrin-like)
Type: Family

Hemerythrin is an oxygen-binding protein. It may be involved in a storage mechanism or delivery to oxygen-requiring enzymes. The oxygen-binding site contains two iron atoms . This entry represents hemerythrin-like proteins from bacteria and archaea .
N-acetyl-D-glucosamine kinase (N-acetyl-D-glucosamine_kinase)
Type: Family

This entry represents N-acetyl-D-glucosamine kinases which catalyse the phosphorylation of N-acetyl-D-glucosamine (GlcNAc) derived from cell-wall degradation, yielding GlcNAc-6-P . This group of proteins belong to the NagK subfamily of the ROK (nagC/xylR) family.
Trans-aconitate 2-methyltransferase (Trans-aconitate_MeTrfase)
Type: Family

Trans-aconitate methyltransferases in bacteria catalyse the monomethyl esterification of trans-aconitate. Trans-aconitate is an effective inhibitor of aconitase, with potentially toxic results, as aconitase plays an essential role in the conversion of citrate to isocitrate in the tricarboxylic acid cycle .
Serine/threonine protein kinase PknD (Ser/Thr_kinase_PknD)
Type: Family

Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process.
Protein kinases fall into three broad classes, characterised with respect to substrate specificity :

Serine/threonine-protein kinases

Tyrosine-protein kinases

Dual specificity protein kinases (e.g. MEK -phosphorylates both Thr and Tyr on target proteins)

Protein kinase function is evolutionarily conserved from Escherichia coli to human . Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved , leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases .

This entry contains the PknD family of serine/threonine protein kinases which are found in (for example) C. trachomatis. In conjunction with Pkn1 they may play a role in specific interactions with host proteins during intracellular growth .
Acetyl esterase (Acetyl_esterase)
Type: Family

Proteins in this entry belong to the 'GDXG' family of lypolytic enzymes and are also known as Aes proteins. They have esterase activity against short chain (up to 8 carbon atoms) fatty esters and are able to hydrolyse triacetin and tributyrin but not triolein or cholesterol oleate. These proteins are involved in the downregulation of the transcriptional activator of the maltose regulon, MalT, in E. coli .
D-aminoacyl-tRNA deacylase-like superfamily (DTD-like_sf)
Type: Homologous_superfamily

D-tyrosyl-tRNA(Tyr) deacylase (DTD), also known as D-aminoacyl-tRNA deacylase, is an editing enzyme that removes D-amino acids from mischarged tRNAs. Structural studies have shown various different modes of D-amino acid recognition by DTDs, suggesting an inherent plasticity that can accommodate all d-amino acids. DTDs are essentially inactive toward L-aa-tRNAs .

This superfamily represents a DTD fold, consisting of a β-barrel closed on one side by a β-sheet lid . The DTD fold is present across the domains of life in two
different functional contexts: as an N-terminal editing domain of archaeal ThrRS (Threonyl-tRNA synthetase), which specifically removes noncognate
L-serine mischarged on tRNAThr, and as a freestanding
'chiral proofreading' enzyme, which removes D-amino acids from
tRNAs in bacteria and eukaryotes .
Methylmalonate-semialdehyde dehydrogenase, Gram-positive bacteria (MSDH_GmP_bac)
Type: Family

Methylmalonate-semialdehyde dehydrogenase (MMSDH,

) catalyses the irreversible NAD+- and CoA-dependent oxidative decarboxylation of methylmalonate semialdehyde to propionyl-CoA. Methylmalonate-semialdehyde dehydrogenase has been characterised in both prokaryotes and eukaryotes , functioning as a mammalian tetramer and a bacterial homodimer. Although similar in monomeric molecular mass and enzymatic activity, the N-terminal sequence in Pseudomonas aeruginosa does not correspond with the N-terminal sequence predicted for rat liver. Sequence homology to a variety of prokaryotic and eukaryotic aldehyde dehydrogenases places MMSDH in the aldehyde dehydrogenase (NAD+) superfamily making MMSDH's CoA requirement unique among known ALDHs. Methylmalonate semialdehyde dehydrogenase is closely related to betaine aldehyde dehydrogenase, 2-hydroxymuconic semialdehyde dehydrogenase, and class 1 and 2 aldehyde dehydrogenase .

This entry represents the Gram-positive proteins involved in inositol metabolism .
Plastocyanin, cyanobacteria (Plastocyanin_cyanobac)
Type: Family

Blue or 'type-1' copper proteins are small proteins which bind a single copper atom and which are characterised by an intense electronic absorption band near 600 nm . The most well known members of this class of proteins are the plant chloroplastic plastocyanins, and the distantly related bacterial azurins, which exchange electrons with cytochrome c551. Plastocyanin participates in electron transfer between the cytochrome b6f complex and photosystem I. Many cyanobacteria and eukaryotic algae can synthesise both plastocyanin and its functional analog cytochrome c6, depending on bioavailabilities of copper and iron, respectively .

Plastocyanin participates in electron transfer between P700 and the cytochrome b/f complex in photosystem I .
Deaminase MtaD/DadD (Deaminase_MtaD/DadD)
Type: Family

This protein family includes MtaD from Thermotoga maritima and a 5'-deoxyadenosine deaminase DadD from Methanocaldococcus jannaschii. MtaD protein has been shown to catalyse the deamination of 5-methylthioadenosine (MTA), S-adenosyl-L-homocysteine (SAH) and adenosine in vitro . DadD protein catalyses the deamination of 5'-deoxyadenosine into 5'-deoxyinosine and may play a role in recycling the radical S-adenosylmethionine enzyme reaction product 5'-deoxyadenosine . Conserved residues present in other members of this family strongly suggest that they have a similar function.
Quinolinate synthase A, type 1 (Quinolinate_synth_A_type1)
Type: Family

This entry represents a group of bacterial type 1 quinolinate synthetases (NadA).

Quinolinate synthetase catalyses the second step of the
de novo
biosynthetic pathway of pyridine nucleotide formation. In particular, quinolinate synthetase is involved in the condensation of dihydroxyacetone phosphate and iminoaspartate to form quinolinic acid . This synthesis requires two enzymes, an FAD-containing "B protein" and an "A protein".
Glyoxylate/hydroxypyruvate reductase A, Enterobacterales (GhrA_Enterobacterales)
Type: Family

This entry represents glyoxylate/hydroxypyruvate reductase A (GrhA) from Enterobacterales. They are implicated in NADPH-dependent reduction of glyoxylate and hydroxypyruvate into glycolate and glycerate, respectively.
Quinolinate synthase A, type 3 (Quinolinate_synth_A_type3)
Type: Family

This entry represents a group of bacterial type 3 quinolinate synthetases (NadA).

Quinolinate synthetase catalyses the second step of the
de novo
biosynthetic pathway of pyridine nucleotide formation. In particular, quinolinate synthetase is involved in the condensation of dihydroxyacetone phosphate and iminoaspartate to form quinolinic acid . This synthesis requires two enzymes, an FAD-containing "B protein" and an "A protein".
tRNA-splicing endonuclease, archaeal long subfamily (tRNA_splic_arch_long)
Type: Family

tRNA-splicing endonucleases (

) catalyse the endonucleolytic cleavage of pre tRNA at the 5' and 3' splice sites to release the intron and produces two half tRNA molecules bearing 5' hydroxyl and 2', 3'-cyclic phosphate termini . The genes encoding these proteins are homologous in eukaryotes and archea. The eukaryotic tRNA-splicing endonucleases are heterotetrameric while the archaeal endonucleases can be split into homodimeric and homotetrameric subgroups.

This group represents the archaeal long tRNA-splicing endonucleases subfamily.
Amino acid/peptide transporter family, dipeptide and tripeptide permease A (AA/pep_transptr_DtpA)
Type: Family

The transport of peptides into cells is a well-documented biological phenomenon which is accomplished by specific, energy-dependent transporters found in a number of organisms as diverse as bacteria and humans. The amino acid/peptide transporter family of proteins is distinct from the ABC-type peptide transporters and was uncovered by sequence analysis of a number of recently discovered peptide transport proteins . This family consists of bacterial proton-dependent oligopeptide transporters, although they are found in yeast, plants and animals. They function by proton symport in a 1:1 stoichiometry, which is variable in different species. Structurally, these transporters present a conserved architecture consisting of 14 transmembrane α-helices with N-terminal and C-terminal six-helix bundles connected by two transmembrane α-helices (HA and HB) .

Dipeptide and tripeptide permease A (DtpA) is a proton-dependent permease that transports di- and tripeptides, and structurally related peptidomimetics such as aminocephalosporins into the cell . The protein shows a distinct preference for dipeptides and tripeptides composed of L-amino acids, and discriminates dipeptides on the basis of the position of charges within the substrate.