SII-SWORD/CoKE huggingface dataset:
Transketolase, N-terminal (Transketolase_N)
Type: Domain

This entry represents the N-terminal domain of a group of transketolase proteins widespread among all cellular organisms.

Transketolase

(TK) catalyses the reversible transfer of a two-carbon ketol unit from xylulose 5-phosphate to an aldose receptor, such as ribose 5-phosphate, to form sedoheptulose 7-phosphate and glyceraldehyde 3- phosphate. This enzyme, together with transaldolase, provides a link between the glycolytic and pentose-phosphate pathways. TK requires thiamine pyrophosphate as a cofactor. In most sources where TK has been purified, it is a homodimer of approximately 70 Kd subunits. TK sequences from a variety of eukaryotic and prokaryotic sources show that the enzyme has been evolutionarily conserved. In the peroxisomes of methylotrophic yeast Pichia angusta (Yeast) (Hansenula polymorpha), there is a highly related enzyme, dihydroxy-acetone synthase (DHAS)

(also known as formaldehyde transketolase), which exhibits a very unusual specificity by including formaldehyde amongst its substrates.

1-deoxyxylulose-5-phosphate synthase (DXP synthase) is an enzyme so far found in bacteria (gene dxs) and plants (gene CLA1) which catalyses the thiamine pyrophosphoate-dependent acyloin condensation reaction between carbon atoms 2 and 3 of pyruvate and glyceraldehyde 3-phosphate to yield 1-deoxy-D-xylulose-5-phosphate (dxp), a precursor in the biosynthetic pathway to isoprenoids, thiamine (vitamin B1), and pyridoxol (vitamin B6). DXP synthase is evolutionary related to TK. The N-terminal section, contains a histidine residue which appears to function in proton transfer during catalysis . This entry represents the central section there are conserved acidic residues that are part of the active cleft and may participate in substrate-binding . This group of proteins includes transketolase enzymes

and 2-oxoisovalerate dehydrogenase beta subunit

. Both these enzymes utilise thiamine pyrophosphate as a cofactor, suggesting there may be common aspects in their mechanism of catalysis.
Transketolase-like, pyrimidine-binding domain (Transketolase-like_Pyr-bd)
Type: Domain

This entry represents the pyrimidine-binding domain of a group of transketolase proteins widespread among all cellular organisms.

Transketolase

(TK) catalyses the reversible transfer of a two-carbon ketol unit from xylulose 5-phosphate to an aldose receptor, such as ribose 5-phosphate, to form sedoheptulose 7-phosphate and glyceraldehyde 3- phosphate. This enzyme, together with transaldolase, provides a link between the glycolytic and pentose-phosphate pathways. TK requires thiamine pyrophosphate as a cofactor. In most sources where TK has been purified, it is a homodimer of approximately 70 Kd subunits. TK sequences from a variety of eukaryotic and prokaryotic sources show that the enzyme has been evolutionarily conserved. In the peroxisomes of methylotrophic yeast Pichia angusta (Yeast) (Hansenula polymorpha), there is a highly related enzyme, dihydroxy-acetone synthase (DHAS)

(also known as formaldehyde transketolase), which exhibits a very unusual specificity by including formaldehyde amongst its substrates.

1-deoxyxylulose-5-phosphate synthase (DXP synthase) is an enzyme so far found in bacteria (gene dxs) and plants (gene CLA1) which catalyses the thiamine pyrophosphoate-dependent acyloin condensation reaction between carbon atoms 2 and 3 of pyruvate and glyceraldehyde 3-phosphate to yield 1-deoxy-D-xylulose-5-phosphate (dxp), a precursor in the biosynthetic pathway to isoprenoids, thiamine (vitamin B1), and pyridoxol (vitamin B6). DXP synthase is evolutionary related to TK. The N-terminal section, contains a histidine residue which appears to function in proton transfer during catalysis . This entry represents the central section there are conserved acidic residues that are part of the active cleft and may participate in substrate-binding . This group of proteins includes transketolase enzymes

and 2-oxoisovalerate dehydrogenase beta subunit

. Both these enzymes utilise thiamine pyrophosphate as a cofactor, suggesting there may be common aspects in their mechanism of catalysis.
Deoxyxylulose-5-phosphate synthase (Dxylulose-5-P_synthase)
Type: Family

1-Deoxy-D-xylulose-5-phosphate synthase (DXP synthase) is a regulatory enzyme of the mevalonate-independent pathway involved in terpenoid biosynthesis. Terpenoids are plant natural products with important pharmaceutical activity. DXP synthase is a thiamine diphosphate-dependent enzyme related to transketolase and the pyruvate dehydrogenase E1-beta subunit. DXP synthase is found in bacteria (gene dxs) and plants (gene CLA1) which catalyses the thiamine pyrophosphoate-dependent acyloin condensation reaction between carbon atoms 2 and 3 of pyruvate and glyceraldehyde 3-phosphate to yield 1-deoxy-D-xylulose-5-phosphate (dxp), a precursor in the biosynthetic pathway to isoprenoids, thiamine (vitamin B1), and pyridoxol (vitamin B6). DXP synthase is evolutionary related to TK. The N-terminal section contains a histidine residue which appears to function in proton transfer during catalysis . In the central section there are conserved acidic residues that are part of the active cleft and may participate in substrate-binding . This family includes transketolase enzymes

, and also partially matches to 2-oxoisovalerate dehydrogenase beta subunit P37941

. Both these enzymes utilise thiamine pyrophosphate as a cofactor, suggesting there may be common aspects in their mechanism of catalysis.
Transketolase, bacterial-like (Transketolase_bac-like)
Type: Family

Transketolase (

) (TK) catalyzes the reversible transfer of a two-carbon ketol unit from xylulose 5-phosphate to an aldose receptor, such as ribose 5-phosphate, to form sedoheptulose 7-phosphate and glyceraldehyde 3-phosphate. This enzyme, together with transaldolase, provides a link between the glycolytic and pentose-phosphate pathways. TK requires thiamine pyrophosphate as a cofactor.
Carbamoyl phosphate synthase, ATP-binding domain (CPAse_ATP-bd)
Type: Domain

This entry represents the ATP-binding domain found in the large subunit of carbamoyl phosphate synthase, as well as in other proteins, including acetyl-CoA carboxylases and pyruvate carboxylases.

Carbamoyl phosphate synthase (CPSase) is a heterodimeric enzyme composed of a small and a large subunit (with the exception of CPSase III, see below). CPSase catalyses the synthesis of carbamoyl phosphate from biocarbonate, ATP and glutamine (

) or ammonia (

), and represents the first committed step in pyrimidine and arginine biosynthesis in prokaryotes and eukaryotes, and in the urea cycle in most terrestrial vertebrates . CPSase has three active sites, one in the small subunit and two in the large subunit. The small subunit contains the glutamine binding site and catalyses the hydrolysis of glutamine to glutamate and ammonia. The large subunit has two homologous carboxy phosphate domains, both of which have ATP-binding sites; however, the N-terminal carboxy phosphate domain catalyses the phosphorylation of biocarbonate, while the C-terminal domain catalyses the phosphorylation of the carbamate intermediate . The carboxy phosphate domain found duplicated in the large subunit of CPSase is also present as a single copy in the biotin-dependent enzymes acetyl-CoA carboxylase (

) (ACC), propionyl-CoA carboxylase (

) (PCCase), pyruvate carboxylase (

) (PC) and urea carboxylase (

).

Most prokaryotes carry one form of CPSase that participates in both arginine and pyrimidine biosynthesis, however certain bacteria can have separate forms. The large subunit in bacterial CPSase has four structural domains: the carboxy phosphate domain 1, the oligomerisation domain, the carbamoyl phosphate domain 2 and the allosteric domain . CPSase heterodimers from Escherichia coli contain two molecular tunnels: an ammonia tunnel and a carbamate tunnel. These inter-domain tunnels connect the three distinct active sites, and function as conduits for the transport of unstable reaction intermediates (ammonia and carbamate) between successive active sites . The catalytic mechanism of CPSase involves the diffusion of carbamate through the interior of the enzyme from the site of synthesis within the N-terminal domain of the large subunit to the site of phosphorylation within the C-terminal domain.

Eukaryotes have two distinct forms of CPSase: a mitochondrial enzyme (CPSase I) that participates in both arginine biosynthesis and the urea cycle; and a cytosolic enzyme (CPSase II) involved in pyrimidine biosynthesis. CPSase II occurs as part of a multi-enzyme complex along with aspartate transcarbamoylase and dihydroorotase; this complex is referred to as the CAD protein . The hepatic expression of CPSase is transcriptionally regulated by glucocorticoids and/or cAMP . There is a third form of the enzyme, CPSase III, found in fish, which uses glutamine as a nitrogen source instead of ammonia . CPSase III is closely related to CPSase I, and is composed of a single polypeptide that may have arisen from gene fusion of the glutaminase and synthetase domains .
Carbamoyl-phosphate synthetase, large subunit oligomerisation domain (CPSase_lsu_oligo)
Type: Domain

This entry represents the oligomerisation domain found in the large subunit of carbamoyl phosphate synthases as well as in certain other carboxy phosphate domain-containing enzymes. This domain forms a primarily α-helical fold .
Biotin carboxylase-like, N-terminal domain (BC-like_N)
Type: Domain

This domain is structurally related to the PreATP-grasp domain. It is found at the N terminus of biotin carboxylase enzymes , and propionyl-CoA carboxylase A chain .
Biotin carboxylase, C-terminal (Biotin_COase_C)
Type: Domain

Acetyl-CoA carboxylase is found in all animals, plants, and bacteria and catalyzes the first committed step in fatty acid synthesis. It is a multicomponent enzyme containing a biotin carboxylase activity, a biotin carboxyl carrier protein, and a carboxyltransferase functionality. The "B-domain" extends from the main body of the subunit where it folds into two α-helical regions and three strands of β-sheet. Following the excursion into the B-domain, the polypeptide chain folds back into the body of the protein where it forms an eight-stranded antiparallel β-sheet. In addition to this major secondary structural element, the C-terminal domain also contains a smaller three-stranded antiparallel β-sheet and seven α-helices .
Carbamoyl phosphate synthase, CPSase domain (CPSase_dom)
Type: Domain

This entry represents the CPSase domain of the large subunit of carbamoyl phosphate synthase.

Carbamoyl phosphate synthase (CPSase) is a heterodimeric enzyme composed of a small and a large subunit (with the exception of CPSase III, see below). CPSase catalyses the synthesis of carbamoyl phosphate from biocarbonate, ATP and glutamine (

) or ammonia (

), and represents the first committed step in pyrimidine and arginine biosynthesis in prokaryotes and eukaryotes, and in the urea cycle in most terrestrial vertebrates . CPSase has three active sites, one in the small subunit and two in the large subunit. The small subunit contains the glutamine binding site and catalyses the hydrolysis of glutamine to glutamate and ammonia. The large subunit has two homologous carboxy phosphate domains, both of which have ATP-binding sites; however, the N-terminal carboxy phosphate domain catalyses the phosphorylation of biocarbonate, while the C-terminal domain catalyses the phosphorylation of the carbamate intermediate . The carboxy phosphate domain found duplicated in the large subunit of CPSase is also present as a single copy in the biotin-dependent enzymes acetyl-CoA carboxylase (

) (ACC), propionyl-CoA carboxylase (

) (PCCase), pyruvate carboxylase (

) (PC) and urea carboxylase (

).

Most prokaryotes carry one form of CPSase that participates in both arginine and pyrimidine biosynthesis, however certain bacteria can have separate forms. The large subunit in bacterial CPSase has four structural domains: the carboxy phosphate domain 1, the oligomerisation domain, the carbamoyl phosphate domain 2 and the allosteric domain . CPSase heterodimers from Escherichia coli contain two molecular tunnels: an ammonia tunnel and a carbamate tunnel. These inter-domain tunnels connect the three distinct active sites, and function as conduits for the transport of unstable reaction intermediates (ammonia and carbamate) between successive active sites . The catalytic mechanism of CPSase involves the diffusion of carbamate through the interior of the enzyme from the site of synthesis within the N-terminal domain of the large subunit to the site of phosphorylation within the C-terminal domain.

Eukaryotes have two distinct forms of CPSase: a mitochondrial enzyme (CPSase I) that participates in both arginine biosynthesis and the urea cycle; and a cytosolic enzyme (CPSase II) involved in pyrimidine biosynthesis. CPSase II occurs as part of a multi-enzyme complex along with aspartate transcarbamoylase and dihydroorotase; this complex is referred to as the CAD protein . The hepatic expression of CPSase is transcriptionally regulated by glucocorticoids and/or cAMP . There is a third form of the enzyme, CPSase III, found in fish, which uses glutamine as a nitrogen source instead of ammonia . CPSase III is closely related to CPSase I, and is composed of a single polypeptide that may have arisen from gene fusion of the glutaminase and synthetase domains .
Large ribosomal subunit protein uL18, bacterial/plantae/animalia (Ribosomal_uL18_bac/plant/anim)
Type: Family

This family includes the large subunit ribosomal protein uL18 from bacteria, mitochondria and plastids.

The large ribosomal subunit protein uL18 is an essential component of the large subunit LSU, which is required in its formation and stabilisation. The LSU contains the ribosomal catalytic site termed the peptidyl transferase centre (PTC), which catalyses the formation of peptide bonds, thereby polymerising the amino acids delivered by tRNAs into a polypeptide chain. Additionally, uL18 is essential for binding and coordinating 5S rRNA into the ribosome, a key step in ribosome biogenesis and assembly .

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 .
Large ribosomal subunit protein uL18, eukaryotic/archaeal (Rbsml_uL18_euk_arch)
Type: Family

This entry represents ribosomal protein uL18 from eukaryotes.

The large ribosomal subunit protein uL18 is an essential component of the large subunit LSU, which is required in its formation and stabilisation. The LSU contains the ribosomal catalytic site termed the peptidyl transferase centre (PTC), which catalyses the formation of peptide bonds, thereby polymerising the amino acids delivered by tRNAs into a polypeptide chain. Additionally, uL18 is essential for binding and coordinating 5S rRNA into the ribosome, a key step in ribosome biogenesis and assembly .

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 .
Glucokinase regulatory protein, conserved site (Glucokinase_regulatory_CS)
Type: Conserved_site

The glucokinase regulatory protein (GCKR) is a vertebrate protein that inhibits glucokinase by forming a complex with the enzyme, which plays a role in the control of blood glucose homeostasis. GCKR is a protein of about 70 Kd which is evolutionary related to bacterial N-acetylmuramic acid 6-phosphate etherases (MurNAc-6-P etherase, murQ), which are about half the size of GCKR and form active homodimers. MurNAc-6-P etherases catalyse the cleavage of the D-lactyl ether substituent of the bacterial cell wall sugar MurNAc and play a role in recycling of the cell wall . The 3D structure of the Haemophilus influenzae HI0754/murQ protein shows structural relationships with other sugar isomerase (SIS) domain proteins. In contrast to mono-SIS bacterial MurNAc-6-P etherase, mammalian GCKR is composed of two SIS domains.
N-acetylmuramic acid 6-phosphate etherase MurQ (Etherase_MurQ)
Type: Family

MurQ is involved in recycling components of the bacterial murein sacculus turned over during cell growth. The cell wall metabolite anhydro-N-acetylmuramic acid (anhMurNAc) is converted by a kinase, AnmK, to MurNAc-phosphate, then converted to N-acetylglucosamine-phosphate by this etherase, called MurQ .
Protein of unknown function DUF257 (DUF257)
Type: Family

This family of proteins is of unknown function.
L,D-transpeptidase catalytic domain (LD_TPept_cat_dom)
Type: Domain

This family of proteins are found in a range of bacteria. The conserved region contains a conserved histidine and cysteine, suggesting that these proteins have an enzymatic activity. Several members of this family contain peptidoglycan binding domains. So these proteins may use peptidoglycan or a precursor as a substrate.
ENT domain (ENT_dom)
Type: Domain

The EMSY N-terminal (ENT) domain is a ~90-residue module, which is unique in the human proteome, although multiple copies are found in Arabidopsis proteins. In the plant proteins, the ENT domains are accompanied by Agenet domains, plant specific homologues of Tudor domains .

The ENT domain consists of a unique arrangement of five α-helices that fold into a helical bundle arrangement. Overall, the three-dimensional structure adopts a club-like shape that consists of an extended N-terminal α-helix that connects to a helical bundle substructure. The ENT domain forms a homodimer via the anti-parallel packing of the long N-terminal α-helix from each subunit .
Leucine-rich glioma-inactivated , EPTP repeat (EPTP)
Type: Repeat

Mutations in the LGI/EPT gene can result in a special form of epilepsy, autosomal dominant lateral temporal epilepsy. The Epitempin protein (also known as Leucine-rich glioma-inactivated protein) was seen to contain a 130 amino acid repeat in its C-terminal section, although a sub-domain of 50 amino acids has now been further defined within this. The architecture and structural features of this repeat make it a likely member 7-bladed β-propeller fold .

This protein has now been found in a number of proteins associated with neurological disorders suggesting that it may play a role in the development of epilepsy and other related conditions .
Ribonuclease E inhibitor RraA/RraA-like protein (RraA/RraA-like)
Type: Family

This entry represents the regulator of ribonuclease E activity A (RraA). These proteins contain a swivelling 3-layer β/β/α domain that appears to be mobile in most multi-domain proteins known to contain it. These proteins are structurally similar, and may have distant homology, to the phosphohistidine domain of pyruvate phosphate dikinase. The RraA fold is an ancient platform that has been adapted for a wide range of functions. RraA had been identified as a putative demethylmenaquinone methyltransferase and was annotated as MenG, but further analysis showed that RraA lacked the structural motifs usually required for methylases .
Glutathionylspermidine synthase, pre-ATP-grasp-like domain (GSPS_pre-ATP-grasp-like_dom)
Type: Domain

Glutathionylspermidine (GSP) synthetases of Trypanosomatidae and Escherichia coli couple hydrolysis of ATP (to ADP and Pi) with formation of an amide bond between spermidine and the glycine carboxylate of glutathione (gamma-Glu-Cys-Gly). In the pathogenic trypanosomatids, this reaction is the penultimate step in the biosynthesis of the antioxidant metabolite, trypanothione (N1,N8-bis-(glutathionyl)spermidine), and is a target for drug design . This domain, which is structurally related to the pre-ATP grasp domain, probably carries the substrate-binding site .
Permease LptG/LptF-related (LptG/LptF_permease)
Type: Family

Members of this family are predicted integral membrane proteins of about 350 amino acids long and containing about 6 transmembrane regions. Characterised members include LptF and LptG, two homologous tandem-encoded permeases of an export ATP transporter for lipopolysaccharide (LPS) assembly in most Gram-negative bacteria .