SII-SWORD/CoKE huggingface dataset:
DNA-directed RNA polymerase, alpha subunit (DNA-dir_RpoA)
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. In eukaryotes, there are three different forms of DNA-directed RNA polymerases transcribing different sets of genes. Most RNA polymerases are multimeric enzymes and are composed of a variable number of subunits. The core RNA polymerase complex consists of five subunits (two alpha, one beta, one beta-prime and one omega) and is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme . The core RNA polymerase complex forms a "crab claw"-like structure with an internal channel running along the full length . The key functional sites of the enzyme, as defined by mutational and cross-linking analysis, are located on the inner wall of this channel.

RNA synthesis follows after the attachment of RNA polymerase to a specific site, the promoter, on the template DNA strand. The RNA synthesis process continues until a termination sequence is reached. The RNA product, which is synthesised in the 5' to 3' direction, is known as the primary transcript.

Eukaryotic nuclei contain three distinct types of RNA polymerases that differ in the RNA they synthesise:

RNA polymerase I: located in the nucleoli, synthesises precursors of most ribosomal RNAs.

RNA polymerase II: occurs in the nucleoplasm, synthesises mRNA precursors.

RNA polymerase III: also occurs in the nucleoplasm, synthesises the precursors of 5S ribosomal RNA, the tRNAs, and a variety of other small nuclear and cytosolic RNAs.

Eukaryotic cells are also known to contain separate mitochondrial and chloroplast RNA polymerases. Eukaryotic RNA polymerases, whose molecular masses vary in size from 500 to 700kDa, contain two non-identical large (>100kDa) subunits and an array of up to 12 different small (less than 50kDa) subunits.

This family consists of the bacterial (and chloroplast) DNA-directed RNA polymerase alpha subunit, encoded by the rpoA gene. The RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. The amino terminal domain is involved in dimerizing and assembling the other RNA polymerase subunits into a transcriptionally active enzyme. The carboxy-terminal domain contains determinants for interaction with DNA and with transcriptional activator proteins .
Geranylgeranyl reductase, plant/cyanobacteria (Geranylgeranyl_Rdtase_pln/cyn)
Type: Family

This entry represents the reductase which acts reduces the geranylgeranyl group to the phytyl group in the side chain of chlorophyll. It is unclear whether the enzyme has a preference for acting before or after the attachment of the side chain to chlorophyllide a by chlorophyll synthase. This clade is restricted to plants and cyanobacteria to separate it from the homologues which act in the biosynthesis of bacteriochlorophyll.
Magnesium chelatase, ATPase subunit I (Mg_chelatase_ATPase-isu)
Type: Family

This entry represents one of two ATPase subunits of the trimeric magnesium chelatase responsible for insertion of magnesium ion into protoporphyrin IX. This is an essential step in the biosynthesis of both chlorophyll and bacteriochlorophyll . This subunit is found in green plants, photosynthetic algae, cyanobacteria and other photosynthetic bacteria. It is also found in certain archaea not known to make chlorins.
Magnesium chelatase, ATPase subunit D (Mg_chelatase_ATPase-dsu)
Type: Family

This entry represents one of two ATPase subunits of the trimeric magnesium chelatase responsible for insertion of magnesium ion into protoporphyrin IX. This is an essential step in the biosynthesis of both chlorophyll and bacteriochlorophyll. This subunit is found in green plants, photosynthetic algae, cyanobacteria and other photosynthetic bacteria. Unlike subunit I (

), this subunit is not found in archaea.
Geranylgeranyl reductase family (Geranylgeranyl_Rdtase_fam)
Type: Family

This entry includes geranylgeranyl reductases involved in chlorophyll and bacteriochlorophyll biosynthesis as well as other related enzymes which may also act on geranylgeranyl groups or related substrates.
Hydantoinase/dihydropyrimidinase (Hydantoinase/dihydroPyrase)
Type: Family

Dihydropyrimidinase (DHPase) catalyses the second step of the reductive pyrimidine degradation, the reversible hydrolytic ring opening of dihydropyrimidines . Primarily converts 5,6-dihydrouracil to N-carbamyl-beta-alanine (also called 3-ureidopropanoate) but also acts on dihydrothymine and hydantoin. The enzyme is a metalloenzyme .

This entry represents the hydantoinase/dihydropyrimidinase family, which also includes D-phenylhydantoinases. This enzyme catalyses the stereospecific hydrolysis of the cyclic amide bond of D-hydantoin derivatives with an aromatic side chains at the 5'-position, and has no activity on dihydropyrimidines .

Dihydropyrimidinase-related proteins (collapsin response mediator proteins, CRMPs) share sequence similarity with liver DHPase. Although purified CRMP does not hydrolyse DHPase substrates, it is likely that a related activity accounts for its participation in neuronal growth cone signaling . CRMP3 has histone H4 deacetylase activity .
Sulphate adenylyltransferase, large subunit (SO4_adenylTrfase_lsu)
Type: Family

Metabolic assimilation of sulphur from inorganic sulphate, requires sulphate activation by coupling to a nucleoside, for the production of high-energy nucleoside phosphosulphates. This pathway appears to be similar in all prokaryotic organisms. Activation is first achieved through sulphation of sulphate with ATP by sulphate adenylyltransferase (ATP sulphurylase) to produce 5'-phosphosulphate (APS), coupled by GTP hydrolysis. Subsequently, APS is phosphorylated by an APS kinase to produce 3'-phosphoadenosine-5'-phosphosulphate (PAPS) . In Escherichia coli, ATP sulphurylase is a heterodimer composed of two subunits encoded by cysD and cysN, with APS kinase encoded by cysC. These genes are located in a unidirectionally transcribed gene cluster, and have been shown to be required for the synthesis of sulphur-containing amino acids . Homologous to this E. coli activation pathway are nodPQH gene products found among members of the Rhizobiaceae family. These gene products have been shown to exhibit ATP sulphurase and APS kinase activity, yet are involved in Nod factor sulphation, and sulphation of other macromolecules . With members of the Rhizobiaceae family, nodQ often appears as a fusion of cysN (large subunit of ATP sulphurase) and cysC (APS kinase) .
D-serine ammonia-lyase (D_Ser_am_lyase)
Type: Family

This family consists of D-serine ammonia-lyases, pyridoxal-phosphate enzymes that convert D-serine to pyruvate and NH3. These enzyme are also called D-serine dehydratase and D-serine deaminase and was previously designated

. It is homologous to an enzyme that acts on threonine and may itself act weakly on threonine.
D-serine deaminase transcriptional activator (DsdC)
Type: Family

This family, part of the LysR family of transcriptional regulators, activates transcription of the gene for D-serine deaminase, dsdA. Trusted members of this family so far are found adjacent to dsdA and only in Gammaproteobacteria, including Escherichia coli, Vibrio cholerae, and Colwellia psychrerythraea (Vibrio psychroerythus).
Peptidase S1C, Do (Pept_S1C_Do)
Type: Family

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes . They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence . Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases .

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base . The geometric orientations of the catalytic residues are similar between families, despite different protein folds . The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) .

This family consists serine peptidases belonging to MEROPS peptidase family S1, subfamily S1C (protease Do, clan PA(S)). They are variously designated DegP, DegQ, heat shock protein HtrA, MucD and protease DO. The ortholog in Pseudomonas aeruginosa is designated MucD and is found in an operon that controls mucoid phenotype. This family also includes the DegQ (HhoA) paralog in Escherichia coli which can rescue a DegP mutant, but not the smaller DegS paralog, which cannot. Members of this family are located in the periplasm and have separable functions as both protease and chaperone. Members have a trypsin domain and two copies of a PDZ domain. This protein protects bacteria from thermal and other stresses and may be important for the survival of bacterial pathogens . The chaperone function is dominant at low temperatures, whereas the proteolytic activity is turned on at elevated temperatures .
Peptidase S1C, DegS (Pept_S1C_DegS)
Type: Family

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes . They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence . Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases .

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base . The geometric orientations of the catalytic residues are similar between families, despite different protein folds . The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) .

This family consists of the periplasmic serine protease DegS (HhoB). They belong to MEROPS peptidase family S1, subfamily S1C (protease Do, clan PA(S)). They are a shorter paralogs of protease Do (HtrA, DegP) and DegQ (HhoA). They are found in Escherichia coli and several of the gammaproteobacteria. DegS contains a trypsin domain and a single copy of PDZ domain (in contrast to DegP with two copies). A critical role of this DegS is to sense stress by detecting misfolded proteins in the periplasm. DegS then cleaves the periplasmic domain of RseA, a transmembrane protein and inhibitor of sigmaE, activating the sigmaE-driven expression of periplasmic proteases/chaperones .
Sulphate adenylyltransferase, small subunit (SO4_adenylTrfase_ssu)
Type: Family

Metabolic assimilation of sulphur from inorganic sulphate, requires sulphate activation by coupling to a nucleoside, for the production of high-energy nucleoside phosphosulphates. This pathway appears to be similar in all prokaryotic organisms. Activation is first achieved through reaction of sulphate with ATP by sulphate adenylyltransferase (ATP sulfurylase) to produce 5'-phosphosulphate (APS), coupled by GTP hydrolysis. Subsequently, APS is phosphorylated by an APS kinase to produce 3'-phosphoadenosine-5'-phosphosulphate (PAPS). In Escherichia coli, ATP sulfurylase is a heterodimer composed of two subunits encoded by cysD and cysN, with APS kinase encoded by cysC. These genes are located in a unidirectionally transcribed gene cluster, and have been shown to be required for the synthesis of sulphur-containing amino acids. Homologous to this E. coli activation pathway are nodPQH gene products found among members of the Rhizobiaceae family. These gene products have been shown to exhibit ATP sulfurase and APS kinase activity, yet are involved in Nod factor sulphation, and sulphation of other macromolecules.
Transcription regulator PpsR (Tscrpt_reg_PpsR-CrtJ)
Type: Family

This entry represents the transcriptional regulator PpsR which is strictly associated with photosynthetic proteobacteria and found in photosynthetic operons. PpsR has been reported to be a repressor . These proteins contain a Helix-Turn-Helix motif of the "fis" type.
Sulphite reductase (NADPH) hemoprotein, beta subunit (CysI)
Type: Family

Sulphite reductase (NADPH) (

) catalyses a six electron reduction of sulfite to sulfide in prokaryotic organisms and is required for the biosynthesis of L-cysteine from sulfate. It is a complex oligomeric enzyme composed of two different peptides with a subunit composition of α(8)-β(4). The alpha component, encoded by cysJ, is a flavoprotein containing both FMN and FAD, while the beta component, encoded by cysI, is a siroheme, iron-sulphur protein .
Sulphite reductase, ferredoxin dependent (SiR_ferredoxin-dep)
Type: Family

Sulphite reductase (ferredoxin) is a cyanobacterial and plant monomeric enzyme distantly related to the iron-sulphur hemoprotein of sulphite reductase (NADPH) found in Proteobacteria and Eubacteria that also catalyses the reduction of sulphite to sulphide . Optimal activity of sulfite reductase (SiR) is essential for normal growth in Arabidopsisis .
Zn(II)-responsive transcriptional regulator (ZntR)
Type: Family

This entry represents the zinc and cadmium (II) responsive transcriptional activator of the gammaproteobacterial zinc efflux system . This protein is a member of the MerR family of transcriptional activators and contains a distinctive pattern of cysteine residues in its metal binding loop, Cys-Cys-X(8-9)-Cys, as well as a conserved and critical cysteine at the N-terminal end of the dimerization helix .
Cu(I)-responsive transcriptional regulator (CueR)
Type: Family

This entry represents the copper-, silver-and gold-(I) responsive transcriptional activator of the gammaproteobacterial copper efflux system . This protein is a member of the MerR family of transcriptional activators and contains a distinctive pattern of cysteine residues in its metal binding loop, Cys-X7-Cys. This family also lacks a conserved cysteine at the N-terminal end of the dimerization helix which is required for the binding of divalent metals such as zinc; here it is replaced by a serine residue .
ADP-specific phosphofructokinase, archaeal (ADP_PFK_arc)
Type: Family

Phosphofructokinase is a key enzyme of glycolysis. The phosphate group donor for different subtypes of phosphofructokinase can be ATP, ADP, or pyrophosphate. This family consists of ADP-dependent phosphofructokinases found in archaea. Members are more similar to ADP-dependent glucokinases (excluded from this family) than to other phosphofructokinases .
Cd(II)/Pb(II)-responsive transcriptional regulator (CadR-PbrR)
Type: Family

This entry represents the cadmium(II) and/or lead(II) responsive transcriptional activator of the proteobacterial metal efflux system . This protein contains a distinctive pattern of cysteine residues in its metal binding loop, Cys-X(6-9)-Cys, as well as a conserved and critical cysteine at the N-terminal end of the dimerization helix .

Pseudomonas aeruginosa CadR and Ralstonia metallidurans PbrR that regulate expression of the cadmium and lead resistance operons, are comprised of distinct domains that harbour the regulatory (effector-binding) site and the active (DNA-binding) site . Their conserved N-terminal domains contain predicted winged helix-turn-helix motifs that mediate DNA binding, while the C-terminal domains have the three conserved cysteines which form a putative metal binding site. Some members in this group have a histidine-rich C-terminal extension. These proteins share the N-terminal DNA binding domain with other transcription regulators of the MerR superfamily that promote transcription by reconfiguring the spacer between the -35 and -10 promoter elements .
Glutamate--cysteine ligase, putative (GshA_cyano)
Type: Family

This family consists of proteins believed to be the glutamate--cysteine ligases of several cyanobacteria, which are known to make glutathione .
Putative glutamate--cysteine ligase YbdK (YbdK)
Type: Family

This entry represents a family of proteins that are thought to function as carboxylate-amine ligases. One protein (

) shows weak glutamate--cysteine ligase activity, but the low catalytic rate casts doubt on whether L-cysteine is the actual biological substrate . Glutamate--cysteine ligase is the first of two enzymes in glutathione biosynthesis. Species in this entry, however, are generally not believed to make glutathione, so their function is unknown.
Hg(II)-responsive transcriptional regulator (MerR)
Type: Family

This entry represents the mercury (II) responsive transcriptional activator of the mer organomercurial resistance operon . This protein is a member of the MerR family of transcriptional activators and contains a distinctive pattern of cysteine residues in its metal binding loop, Cys-X(8)-Cys-Pro, as well as a conserved and critical cysteine at the N-terminal end of the dimerization helix .

MerR1 transcription regulators, such as Tn21 MerR and Tn501 MerR, mediate response to mercury exposure in eubacteria . These proteins are comprised of distinct domains that harbour the regulatory (effector-binding) site and the active (DNA-binding) site. Their conserved N-terminal domains contain winged HTH motifs that mediate DNA binding, while the C-terminal domains have three conserved cysteines that define a mercury binding site . These proteins share the N-terminal DNA binding domain with other transcription regulators of the MerR superfamily that promote transcription by reconfiguring the spacer between the -35 and -10 promoter elements .
Mercuric transport protein periplasmic component (MerP)
Type: Family

This entry represents the periplasmic mercury (II) binding protein of the bacterial mercury detoxification system which passes mercuric ion to the MerT transporter for subsequent reduction to Hg(0) by the mercuric reductase MerA . MerP contains a distinctive GMTCXXC motif associated with metal binding . MerP is related to a larger family of metal binding proteins.
Mercuric resistence transcriptional repressor protein MerD (MerD)
Type: Family

This entry represents a transcriptional repressor protein of the MerR family whose expression is regulated by the mercury-sensitive transcriptional activator, MerR. MerD has been shown to repress the transcription of the mer operon .
Adenosine 5'-phosphosulphate reductase (APS_reductase)
Type: Family

This entry describes recently identified adenosine 5'-phosphosulphate (APS) reductases found in sulphate-assimilatory prokaryotes . They are homologous to phosphoadenosine phosphosulphate (PAPS) reductase in enterobacteria, cyanobacteria, and yeast, and perform the same overall function in activating inorganic sulphate. They also show detectable homology with plant APS reductase. The presence of two conserved C-terminal motifs (CCXXRKXXPL and SXGCXXCT), thought to form an iron-sulphur cluster distinguishes APS reductases from PAPS reductases.
Chlorophyll synthase, ChlG (ChlG)
Type: Family

This entry represents the strictly cyanobacterial and plant-specific chlorophyll synthase ChlG. ChlG is the enzyme (esterase) which attaches the side chain moiety onto chlorophyllide a. Both geranylgeranyl and phytyl pyrophosphates are substrates to varying degrees in enzymes from different sources . Thus, ChlG may act as the final or penultimate step in chlorophyll biosynthesis (along with the geranylgeranyl reductase, ChlP).
Phosphoadenosine phosphosulphate reductase CysH (PAPS_reductase_CysH)
Type: Family

Requiring thioredoxin as an electron donor, phosphoadenosine phosphosulphate reductase catalyzes the reduction of phosphoadenosine phosphosulphate (PAPS) to sulphite and phosphoadenosine phosphate (PAP) . Found in enterobacteria, cyanobacteria, and yeast, PAPS reductase is related to a group of plant (

) and bacterial (

) enzymes preferring 5'-adenylylsulphate (APS) over PAPS as a substrate for reduction to sulphite .
Cyanobacterial long protein repeat (Swm_rep_I_cyn)
Type: Repeat

This motif appears in 29 copies in a large (greater than 10000 amino protein in Synechococcus sp. (strain WH8102) associated with a novel flagellar system, as one of three different repeats. Similar domains are found in two different large (less than 3500 amino acid) proteins of Synechocystis sp. (strain PCC 6803).
Adenylylsulphate reductase, beta subunit (AprB)
Type: Family

During dissimilatory sulphate reduction and sulphur oxidation, adenylylsulphate (APS) reductase catalyzes reversibly the two-electron reduction of APS to sulphite and AMP. Found in several bacterial lineages and in Archaeoglobales, APS reductase is a heterodimer composed of an alpha subunit containing a noncovalently bound FAD, and a beta subunit containing two [4Fe-4S] clusters. This entry describes the beta subunit of APS reductase, which shares a common evolutionary origin with other iron-sulphur cluster-binding proteins.
Adenylylsulphate reductase, alpha subunit (AprA)
Type: Family

Adenylylsulphate (APS) reductase catalyses reversibly the two-electron reduction of APS to sulphite and AMP during dissimilatory sulphate reduction or sulphur oxidation. Found in several bacterial lineages and in Archaeoglobales, APS reductase is a heterodimer composed of an alpha subunit containing a noncovalently bound FAD, and a beta subunit containing two [4Fe-4S] clusters. The alpha subunit of APS reductase shares a common evolutionary origin with fumarate reductase/succinate dehydrogenase flavoproteins .
Ribonuclease II (RNase_II)
Type: Family

This family consists of exoribonuclease II (RNase II), the product of the rnb gene, as found in a number of gamma proteobacteria. In Escherichia coli, it is one of eight different exoribonucleases. It is involved in mRNA degradation and tRNA precursor end processing .
Ribonuclease R (RNase_R)
Type: Family

Ribonuclease R (RNaseR) is a 3'-5' exoribonuclease that releases 5'-nucleoside monophosphates and is involved in maturation of structured RNAs . It is one of the eight exoribonucleases reported in Escherichia coli and is broadly distributed throughout the bacteria. In E. coli, double mutants of this protein and polynucleotide phosphorylase are not viable. RNaseR also exhibits helicase activity that appears to be independent of its RNase activity .
Sulphite reductase, dissimilatory-type alpha subunit (DsrA)
Type: Family

Dissimilatory sulphite reductase catalyzes the six-electron reduction of sulphite to sulphide, as the terminal reaction in dissimilatory sulphate reduction. It remains unclear however, whether trithionate and thiosulphate serve as intermediate compounds to sulphide, or as end products of sulphite reduction . Sulphite reductase is a multisubunit enzyme composed of dimers of either alpha/beta or alpha/beta/gamma subunits, each containing a siroheme and iron sulphur cluster prosthetic centre . Found in sulphate-reducing bacteria, these genes are commonly located in a unidirectional gene cluster .