SII-SWORD/CoKE huggingface dataset:
Small ribosomal subunit protein uS7, conserved site (Ribosomal_uS7_CS)
Type: Conserved_site

This entry represents a conserved site located in the N-terminal section of the proteins.

This entry includes the small ribosomal subunit protein uS7, formerly referred to as 30S ribosomal proteins S7 (bacterial, archaeal, plastid, mitochondrial), and eukaryotic 40S ribosomal proteins S5 (cytoplasmic) . 30S ribosomal protein S7 contacts ribosomal proteins S9 and S11. It is also one of the primary rRNA binding proteins - it binds directly to 16S rRNA - where it nucleates assembly of the head domain of the 30S subunit . S7 is located at the subunit interface close to the decoding centre, where it has been shown to contact mRNA. It has also been shown to contact tRNA in both the P and E sites; it probably blocks exit of the E site tRNA.

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 .
DNA primase DnaG, archaea (Primase_DnaG_arc)
Type: Family

Archaeal DnaG proteins contain a central TOPRIM domain, which is characteristic for topoisomerases and primases. DnaG from Sulfolobus solfataricus has been shown to exhibit primase activity ,
catalysing the synthesis of short RNA molecules used as primers for DNA polymerase during DNA replication. The protein has been linked to the RNA exosome complex, having been shown to be a poly(A)-binding protein in S. solfataricus that forms part of the heteromeric, RNA-binding cap of the exosome .
RNA polymerase, subunit H/Rpb5, conserved site (RNA_pol_subH/Rpb5_CS)
Type: Conserved_site

Prokaryotes contain a single DNA-dependent RNA polymerase (RNAP;

) that is responsible for the transcription of all genes, while eukaryotes have three classes of RNAPs (I-III) that transcribe different sets of genes. Each class of RNA polymerase is an assemblage of ten to twelve different polypeptides. Certain subunits of RNAPs, including RPB5 (POLR2E in mammals), are common to all three eukaryotic polymerases. RPB5 plays a role in the transcription activation process. Eukaryotic RPB5 has a bipartite structure consisting of a unique N-terminal region (

), plus a C-terminal region that is structurally homologous to the prokaryotic RPB5 homologue, subunit H (gene rpoH) .

This entry represents a conserved site of RNA polymerase, subunit H/Rpb5.
Thiolase, active site (Thiolase_AS)
Type: Active_site

Two different types of thiolase are found both in eukaryotes and in prokaryotes: acetoacetyl-CoA thiolase (

) and 3-ketoacyl-CoA thiolase (

). 3-ketoacyl-CoA thiolase (also called thiolase I) has a broad chain-length specificity for its substrates and is involved in degradative pathways such as fatty acid beta-oxidation. Acetoacetyl-CoA thiolase (also called thiolase II) is specific for the thiolysis of acetoacetyl-CoA and involved in biosynthetic pathways such as poly beta-hydroxybutyrate synthesis or steroid biogenesis.

In eukaryotes, there are two forms of 3-ketoacyl-CoA thiolase: one located in the mitochondrion and the other in peroxisomes.

Mammalian nonspecific lipid-transfer protein (nsL-TP) (also known as sterol carrier protein 2) is a protein which seems to exist in two different forms: a 14 Kd protein (SCP-2) and a larger 58 Kd protein (SCP-x). The former is found in the cytoplasm or the mitochondria and is involved in lipid transport; the latter is found in peroxisomes. The C-terminal part of SCP-x is identical to SCP-2 while the N-terminal portion is evolutionary related to thiolases .

There are two conserved cysteine residues important for thiolase activity. The first located in the N-terminal section of the enzymes is involved in the formation of an acyl-enzyme intermediate; the second, which is found in the signature pattern in this entry, is located at the C-terminal extremity and is the active site base involved in deprotonation in the condensation reaction .
Copper type II, ascorbate-dependent monooxygenase, histidine-cluster-1 conserved site (Cu2_ascorb_mOase_CS-1)
Type: Conserved_site

Copper type II, ascorbate-dependent monooxygenases are a class of enzymes that requires copper as a cofactor and which uses ascorbate as an electron donor. This family contains two related enzymes, dopamine-beta-monooxygenase (

) and peptidyl-glycine alpha-amidating monooxygenase (

). There are a few regions of sequence similarities between these two enzymes, two of these regions contain clusters of conserved histidine residues which are most probably involved in binding copper.

This entry represents a conserved site that covers the first cluster of conserved histidine residues.
Methylthiotransferase, conserved site (Methylthiotransferase_CS)
Type: Conserved_site

The methylthiotransferase (MTTase) or miaB-like family is named after the (dimethylallyl)adenosine tRNA MTTase miaB protein, which catalyses a C-H to C-S bond conversion in the methylthiolation of tRNA. A related bacterial enzyme rimO performs a similar methylthiolation, but on a protein substrate. RimO acts on the ribosomal protein S12 and forms a separate MTTase subfamily. The miaB-subfamily includes mammalian CDK5 regulatory subunit-associated proteins and similar proteins in other eukaryotes. Two other subfamilies, yqeV and CDKAL1, are named after a Bacillus subtilis and a human protein, respectively. While yqeV-like proteins are found in bacteria, CDKAL1 subfamily members occur in eukaryotes and in archaebacteria. The likely MTTases from these 4 subfamilies contain an N-terminal MTTase domain, a central radical generating fold and a C-terminal TRAM domain (see

). The core forms a radical SAM fold (or AdoMet radical), containing a cysteine motif CxxxCxxC that binds a [4Fe-4S] cluster . A reducing equivalent from the [4Fe-4S]+ cluster is used to cleave S-adenosylmethionine (SAM) to generate methionine and a 5'-deoxyadenosyl radical. The latter is thought to produce a reactive substrate radical that is amenable to sulphur insertion . The N-terminal MTTase domain contains 3 cysteines that bind a second [4Fe-4S] cluster, in addition to the radical-generating [4Fe-4S] cluster, which could be involved in the thiolation reaction. The C-terminal TRAM domain is not shared with other radical SAM proteins outside the MTTase family. The TRAM domain can bind to RNA substrate and seems to be important for substrate recognition. The tertiary structure of the central radical SAM fold has six β/α motifs resembling a three-quarter TIM barrel core (see

) . The N-terminal MTTase domain might form an additional [β/α]2 TIM barrel unit .

This entry represents a conserved site containing three of the conserved cysteines that form the motif in the central radical SAM fold.
Thiolase, conserved site (Thiolase_CS)
Type: Conserved_site

Two different types of thiolase are found both in eukaryotes and in prokaryotes: acetoacetyl-CoA thiolase (

) and 3-ketoacyl-CoA thiolase (

). 3-ketoacyl-CoA thiolase (also called thiolase I) has a broad chain-length specificity for its substrates and is involved in degradative pathways such as fatty acid beta-oxidation. Acetoacetyl-CoA thiolase (also called thiolase II) is specific for the thiolysis of acetoacetyl-CoA and involved in biosynthetic pathways such as poly beta-hydroxybutyrate synthesis or steroid biogenesis.

In eukaryotes, there are two forms of 3-ketoacyl-CoA thiolase: one located in the mitochondrion and the other in peroxisomes.

There are two conserved cysteine residues important for thiolase activity. The first located in the N-terminal section of the enzymes is involved in the formation of an acyl-enzyme intermediate; the second located at the C-terminal extremity is the active site base involved in deprotonation in the condensation reaction .

Mammalian nonspecific lipid-transfer protein (nsL-TP) (also known as sterol carrier protein 2) is a protein which seems to exist in two different forms: a 14 Kd protein (SCP-2) and a larger 58 Kd protein (SCP-x). The former is found in the cytoplasm or the mitochondria and is involved in lipid transport; the latter is found in peroxisomes. The C-terminal part of SCP-x is identical to SCP-2 while the N-terminal portion is evolutionary related to thiolases .

The signature pattern for this entry is a conserved sequence located towards the C-terminal end.
Thiolase, acyl-enzyme intermediate active site (Thiolase_acyl_enz_int_AS)
Type: Active_site

Two different types of thiolase are found both in eukaryotes and in prokaryotes: acetoacetyl-CoA thiolase (

) and 3-ketoacyl-CoA thiolase (

). 3-ketoacyl-CoA thiolase (also called thiolase I) has a broad chain-length specificity for its substrates and is involved in degradative pathways such as fatty acid beta-oxidation. Acetoacetyl-CoA thiolase (also called thiolase II) is specific for the thiolysis of acetoacetyl-CoA and involved in biosynthetic pathways such as poly beta-hydroxybutyrate synthesis or steroid biogenesis.

In eukaryotes, there are two forms of 3-ketoacyl-CoA thiolase: one located in the mitochondrion and the other in peroxisomes.

Mammalian nonspecific lipid-transfer protein (nsL-TP) (also known as sterol carrier protein 2) is a protein which seems to exist in two different forms: a 14 Kd protein (SCP-2) and a larger 58 Kd protein (SCP-x). The former is found in the cytoplasm or the mitochondria and is involved in lipid transport; the latter is found in peroxisomes. The C-terminal part of SCP-x is identical to SCP-2 while the N-terminal portion is evolutionary related to thiolases .

There are two conserved cysteine residues important for thiolase activity. The signature pattern for this entry contains the first conserved cysteine located in the N-terminal section of the enzymes, which is involved in the formation of an acyl-enzyme intermediate; the second located at the C-terminal extremity is the active site base involved in deprotonation in the condensation reaction .
Thiolase, N-terminal (Thiolase_N)
Type: Domain

This entry represents the N-terminal domain of thiolases and related proteins.

Two different types of thiolase are found both in eukaryotes and in prokaryotes: acetoacetyl-CoA thiolase (

) and 3-ketoacyl-CoA thiolase (

). 3-ketoacyl-CoA thiolase (also called thiolase I) has a broad chain-length specificity for its substrates and is involved in degradative pathways such as fatty acid beta-oxidation. Acetoacetyl-CoA thiolase (also called thiolase II) is specific for the thiolysis of acetoacetyl-CoA and involved in biosynthetic pathways such as poly beta-hydroxybutyrate synthesis or steroid biogenesis.

In eukaryotes, there are two forms of 3-ketoacyl-CoA thiolase: one located in the mitochondrion and the other in peroxisomes.

There are two conserved cysteine residues important for thiolase activity. The first located in the N-terminal section of the enzymes is involved in the formation of an acyl-enzyme intermediate; the second located at the C-terminal extremity is the active site base involved in deprotonation in the condensation reaction.

Mammalian nonspecific lipid-transfer protein (nsL-TP) (also known as sterol carrier protein 2) is a protein which seems to exist in two different forms: a 14 Kd protein (SCP-2) and a larger 58 Kd protein (SCP-x). The former is found in the cytoplasm or the mitochondria and is involved in lipid transport; the latter is found in peroxisomes. The C-terminal part of SCP-x is identical to SCP-2 while the N-terminal portion is evolutionary related to thiolases .
Thiolase, C-terminal (Thiolase_C)
Type: Domain

This entry represents the C-terminal domain of thiolases and related proteins.

Two different types of thiolase are found both in eukaryotes and in prokaryotes: acetoacetyl-CoA thiolase (

) and 3-ketoacyl-CoA thiolase (

). 3-ketoacyl-CoA thiolase (also called thiolase I) has a broad chain-length specificity for its substrates and is involved in degradative pathways such as fatty acid beta-oxidation. Acetoacetyl-CoA thiolase (also called thiolase II) is specific for the thiolysis of acetoacetyl-CoA and involved in biosynthetic pathways such as poly beta-hydroxybutyrate synthesis or steroid biogenesis.

In eukaryotes, there are two forms of 3-ketoacyl-CoA thiolase: one located in the mitochondrion and the other in peroxisomes.

There are two conserved cysteine residues important for thiolase activity. The first located in the N-terminal section of the enzymes is involved in the formation of an acyl-enzyme intermediate; the second located at the C-terminal extremity is the active site base involved in deprotonation in the condensation reaction.

Mammalian nonspecific lipid-transfer protein (nsL-TP) (also known as sterol carrier protein 2) is a protein which seems to exist in two different forms: a 14 Kd protein (SCP-2) and a larger 58 Kd protein (SCP-x). The former is found in the cytoplasm or the mitochondria and is involved in lipid transport; the latter is found in peroxisomes. The C-terminal part of SCP-x is identical to SCP-2 while the N-terminal portion is evolutionary related to thiolases .
Adenylate kinase isoenzyme 6 (Adenyl_kinase_AK6)
Type: Family

Adenylate kinase isoenzyme 6 (AK6) is a broad-specificity nucleoside monophosphate (NMP) kinase that catalyses the reversible transfer of the terminal phosphate group between nucleoside triphosphates and monophosphates . AMP and dAMP are the preferred substrates, but CMP and dCMP are also good substrates. All nucleoside triphosphates ATP, GTP, UTP, CTP, dATP, dCTP, dGTP, and TTP are accepted as phosphate donors. It has also ATPase activity and may have a role in nuclear energy homeostasis. AK6 is involved in regulation of Cajal body (CB) formation .

This entry also includes related putative adenylate kinases from archaea.
ATP phosphoribosyltransferase HisG, long form (ATP-PRT_HisG_long)
Type: Family

ATP phosphoribosyltransferase (ATP-PRT,

) is the enzyme that catalyses the first step in the biosynthesis of histidine in bacteria, fungi and plants as shown below. It is a member of the larger phosphoribosyltransferase superfamily of enzymes which catalyse the condensation of 5-phospho-alpha-D-ribose 1-diphosphate with nitrogenous bases in the presence of divalent metal ions .

ATP + 5-phospho-alpha-D-ribose 1-diphosphate = 1-(5-phospho-D-ribosyl)-ATP + diphosphate

Histidine biosynthesis is an energetically expensive process and ATP-PRT activity is subject to control at several levels. Transcriptional regulation is based primarily on nutrient conditions and determines the amount of enzyme present in the cell, while feedback inhibition rapidly modulates activity in response to cellular conditions. The enzyme has been shown to be inhibited by 1-(5-phospho-D-ribosyl)-ATP, histidine, ppGpp (a signal associated with adverse environmental conditions) and ADP and AMP (which reflect the overall energy status of the cell). As this pathway of histidine biosynthesis is present only in prokaryotes, plants and fungi, this enzyme is a promising target for the development of novel antimicrobial compounds and herbicides.

ATP-PRT come in two forms: a long form containing two catalytic domains and a C-terminal regulatory domain, and a short form in which the regulatory domain is missing. The long form is catalytically competent, but in organisms with the short form, a histidyl-tRNA synthetase paralogue, HisZ, is required for enzyme activity .

The enzyme was initially thought to exist in equilibrium between an active dimeric form, an inactive hexameric form and higher aggregates . However, it has been shown later that this protein is a hexamer in equilibrium between an open and probably active state and a more compact closed and presumably inhibited form. These conformational changes are related to the allosteric inhibition by histidine. The ATP-PRT from Campylobacter jejuni is organised into three domains. The first two domains form a bilobal core unit that harbours the catalytic site in the cleft between them, where the binding of ATP and AMP is observed, and the C-terminal is a regulatory ACT domain, which binds histidine .

This entry represents the long form ATP phosphoribosyltransferase.
Alanine racemase, pyridoxal-phosphate attachment site (Ala_racemase_pyridoxalP-BS)
Type: Binding_site

Alanine racemase catalyses the pyridoxal-dependent conversion of L-alanine into D-alanine, a key component of bacterial peptidoglycan . In Escherichia coli and Salmonella typhimurium, there are two alanine racemase isoforms, alr is a biosynthetic form required for cell wall formation; and dadB functions in L-alanine catabolism. By contrast with dadB and alr, both of which are monomeric enzymes, the alanine racemase of Bacillaceae are homodimers. In Pseudomonas putida, a broad-specificity amino acid racemase is structurally and functionally related to alanine racemase. The 3D-structure of the dimeric alanine racemase from Bacillus stearothermophilus has been determined to a resolution of 1.9 A . Each monomer comprises two domains, with an eight-stranded α/β barrel at the N terminus, and a C-terminal β-strand domain. In the dimer, the mouth of the α/β barrel of one monomer faces the second domain of the other monomer. The pyridoxal 5'-phosphate (PLP) cofactor lies in and above the barrel mouth and is covalently linked via an aldimine linkage to Lys39. Several other residues are involved in anchoring the PLP, for example, Arg219 forms a hydrogen bond with the pyridine nitrogen of the cofactor, which is assumed to influence electron delocalisation in PLP-alanine intermediates; Arg136 donates a hydrogen bond to the phenolic oxygen of PLP, and may be involved in substrate binding and stabilisation of intermediates; and Tyr265' is postulated to be a 2 proton donor to the carbanion intermediate .

This pattern signature contains the lysine residue of alanine racemase that acts as the attachment site for the pyridoxal-phosphate group. The sequence around this residue is highly conserved in all forms of the enzyme.
Schiff base-forming aldolase, conserved site (Schiff_base-form_aldolases_CS)
Type: Conserved_site

This entry represents an conserved site found in members of a structural superfamily of Schiff base-forming aldolases that catalyse reactions in different biological pathways. This superfamily includes members such as dihydrodipicolinate synthase (DHDPS), N-acetylneuraminate lyase (NAL) and 2-keto-3-deoxygluconate aldolase (KDG aldolase) . One of the Escherichia coli proteins containing this site, dapA (

), was first identified as dihydrodipicolinate synthase (DHDPS) . Later, it has been identified as 4-hydroxy-tetrahydrodipicolinate synthases (

) .
Schiff base-forming aldolase, active site (Schiff_base-form_aldolases_AS)
Type: Active_site

This entry represents an active site found in members of a structural superfamily of Schiff base-forming aldolases that catalyse reactions in different biological pathways. This superfamily includes members such as dihydrodipicolinate synthase (DHDPS), N-acetylneuraminate lyase (NAL) and 2-keto-3-deoxygluconate aldolase (KDG aldolase) . One of the Escherichia coli proteins containing this site, dapA (

), was first identified as dihydrodipicolinate synthase (DHDPS) . Later, it has been identified as 4-hydroxy-tetrahydrodipicolinate synthases (

) .
L-aspartate dehydrogenase, prokaryotic (Asp_DH_prok)
Type: Family

This group contains aspartate dehydrogenases that belong to a unique class of amino acid dehydrogenases.

The structure of Thermotoga maritima TM1643 has been found to contain an N-terminal Rossmann fold domain (which binds the NAD(P)
+
cofactor) and a C-terminal α/β domain . This suggested that TM1643 may be a dehydrogenase with the active
site located at the interface between the two domains. Enzymatic characterisation of TM1643 revealed that it possesses NAD or NADP-dependent dehydrogenase activity toward L-aspartate but no aspartate oxidase activity . The product of the aspartate dehydrogenase activity is also iminoaspartate. It has been suggested that two different enzymes, an oxidase and a dehydrogenase, may have evolved to catalyse the
first step of NAD biosynthesis . Members of this group share some structural similarity to several other NAD(P)
+
-dependent oxidoreductases, including inositol 1-phosphate synthase, dihydrodipicolinate reductase, and ASA-DH .

It has been proposed that in Thermotoga maritima, TM1643 catalyses the first reaction of de novo biosynthesis of NAD from aspartate, and it produces iminoaspartate required for this pathway. The formation of an enzyme complex between TM1643 and NadA, the next enzyme of the pathway, may allow the channeling of this unstable product directly to the NadA active site .

This entry is restricted to bacterial and archaeal enzymes.
RNA-binding protein KhpA (KhpA)
Type: Family

This family represents the RNA-binding protein KhpA, a probable RNA chaperone. It forms a complex with KhpB (also known as Jag or EloR) which binds to cellular RNA and controls its expression. KhpA plays a role in peptidoglycan (PG) homeostasis and cell length regulation . The KhpA-KhpB complex stimulates or controls elongasome-mediated lateral cell wall biosynthesis. It is not clear what is the function of the KhpA homooligomer in vivo . KhpA forms homodimers, additionally, it interacts with the KH-II domain of EloR, a key regulator of cell elongation in S. pneumoniae, forming an EloR/KhpA heterodimer .