SII-SWORD/CoKE huggingface dataset:
Large ribosomal subunit protein uL2, C-terminal (Ribosomal_uL2_C)
Type: Domain

This entry represents the C-terminal domain of the large ribosomal subunit protein uL2.

Ribosomal protein uL2 is one of the proteins from the large ribosomal subunit. The best conserved region is located in the C-terminal section of these proteins. In Escherichia coli, uL2 is known to bind to the 23S rRNA and to have peptidyltransferase activity. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities , groups:

Eubacterial uL2 (old name L2).

Algal and plant chloroplast uL2 (old name L2).

Cyanelle uL2 (old name L2).

Archaebacterial uL2 (old name L2).

Plant uL2 (old name L2).

Slime mold uL2 (old name L2).

Marchantia polymorpha mitochondrial uL2m (old name L2).

Paramecium tetraurelia mitochondrial uL2m (old name L2).

Fission yeast K5, K37 and KD4.

Yeast YL6.

Vertebrate uL2 (old name L8).

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 uL2, conserved site (Ribosomal_uL2_CS)
Type: Conserved_site

This entry represents the best conserved region located in the C-terminal section of the large ribosomal subunit protein uL2.

Ribosomal protein uL2 is one of the proteins from the large ribosomal subunit. The best conserved region is located in the C-terminal section of these proteins. In Escherichia coli, uL2 is known to bind to the 23S rRNA and to have peptidyltransferase activity. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities , groups:

Eubacterial uL2 (old name L2).

Algal and plant chloroplast uL2 (old name L2).

Cyanelle uL2 (old name L2).

Archaebacterial uL2 (old name L2).

Plant uL2 (old name L2).

Slime mold uL2 (old name L2).

Marchantia polymorpha mitochondrial uL2m (old name L2).

Paramecium tetraurelia mitochondrial uL2m (old name L2).

Fission yeast K5, K37 and KD4.

Yeast YL6.

Vertebrate uL2 (old name L8).

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 .
Hexokinase, N-terminal (Hexokinase_N)
Type: Domain

Hexokinase is an important enzyme that catalyses the ATP-dependent conversion of aldo- and keto-hexose sugars to the hexose-6-phosphate (H6P). The enzyme can catalyse this reaction on glucose, fructose, sorbitol and glucosamine, and as such is the first step in a number of metabolic pathways . The addition of a phosphate group to the sugar acts to trap it in a cell, since the negatively charged phosphate cannot easily traverse the plasma membrane.

The enzyme is widely distributed in eukaryotes. There are three isozymes of hexokinase in yeast Hxk1, Hxk2, and Glk1 (or PI, PII and glucokinase, respectively): isozymes PI and PII phosphorylate both aldo- and keto-sugars; glucokinase is specific for aldohexoses. All three isozymes contain two domains . There have been described two hexokinase-like proteins in yeast, namely Putative glucokinase-2 (Emi2) and N-acetylglucosamine kinase (YLR446W) . Structural studies of yeast hexokinase reveal a well-defined catalytic pocket that binds ATP and hexose, allowing easy transfer of the phosphate from ATP to the sugar . Vertebrates contain four hexokinase isozymes, designated I to IV, where types I to III contain a duplication of the two-domain yeast-type hexokinases. Both the N- and C-terminal halves bind hexose and H6P, though in types I an III only the C-terminal half supports catalysis, while both halves support catalysis in type II. The N-terminal half is the regulatory region. Type IV hexokinase is similar to the yeast enzyme in containing only the two domains, and is sometimes incorrectly referred to as glucokinase.

The different vertebrate isozymes differ in their catalysis, localisation and regulation, thereby contributing to the different patterns of glucose metabolism in different tissues . Whereas types I to III can phosphorylate a variety of hexose sugars and are inhibited by glucose-6-phosphate (G6P), type IV is specific for glucose and shows no G6P inhibition. Type I enzyme may have a catabolic function, producing H6P for energy production in glycolysis; it is bound to the mitochondrial membrane, which enables the coordination of glycolysis with the TCA cycle. Types II and III enzyme may have anabolic functions, providing H6P for glycogen or lipid synthesis. Type IV enzyme is found in the liver and pancreatic beta-cells, where it is controlled by insulin (activation) and glucagon (inhibition). In pancreatic beta-cells, type IV enzyme acts as a glucose sensor to modify insulin secretion. Mutations in type IV hexokinase have been associated with diabetes mellitus.

Hexokinase (

), a fructose and glucose phosphorylating enzyme, contains two structurally similar domains represented by this family and

. Some hexokinases have two copies of each of these domains. This entry represents the N-terminal domain.
Hexokinase, C-terminal (Hexokinase_C)
Type: Domain

Hexokinase is an important enzyme that catalyses the ATP-dependent conversion of aldo- and keto-hexose sugars to the hexose-6-phosphate (H6P). The enzyme can catalyse this reaction on glucose, fructose, sorbitol and glucosamine, and as such is the first step in a number of metabolic pathways . The addition of a phosphate group to the sugar acts to trap it in a cell, since the negatively charged phosphate cannot easily traverse the plasma membrane.

The enzyme is widely distributed in eukaryotes. There are three isozymes of hexokinase in yeast Hxk1, Hxk2, and Glk1 (or PI, PII and glucokinase, respectively): isozymes PI and PII phosphorylate both aldo- and keto-sugars; glucokinase is specific for aldohexoses. All three isozymes contain two domains . There have been described two hexokinase-like proteins in yeast, namely Putative glucokinase-2 (Emi2) and N-acetylglucosamine kinase (YLR446W) . Structural studies of yeast hexokinase reveal a well-defined catalytic pocket that binds ATP and hexose, allowing easy transfer of the phosphate from ATP to the sugar . Vertebrates contain four hexokinase isozymes, designated I to IV, where types I to III contain a duplication of the two-domain yeast-type hexokinases. Both the N- and C-terminal halves bind hexose and H6P, though in types I an III only the C-terminal half supports catalysis, while both halves support catalysis in type II. The N-terminal half is the regulatory region. Type IV hexokinase is similar to the yeast enzyme in containing only the two domains, and is sometimes incorrectly referred to as glucokinase.

The different vertebrate isozymes differ in their catalysis, localisation and regulation, thereby contributing to the different patterns of glucose metabolism in different tissues . Whereas types I to III can phosphorylate a variety of hexose sugars and are inhibited by glucose-6-phosphate (G6P), type IV is specific for glucose and shows no G6P inhibition. Type I enzyme may have a catabolic function, producing H6P for energy production in glycolysis; it is bound to the mitochondrial membrane, which enables the coordination of glycolysis with the TCA cycle. Types II and III enzyme may have anabolic functions, providing H6P for glycogen or lipid synthesis. Type IV enzyme is found in the liver and pancreatic beta-cells, where it is controlled by insulin (activation) and glucagon (inhibition). In pancreatic beta-cells, type IV enzyme acts as a glucose sensor to modify insulin secretion. Mutations in type IV hexokinase have been associated with diabetes mellitus.

Hexokinase (

), a fructose and glucose phosphorylating enzyme, contains two structurally similar domains represented by this family and

. Some members of the family have two copies of each of these domains. This entry represents the more C-terminal domain.
Glucose-6-phosphate dehydrogenase, NAD-binding (G6P_DH_NAD-bd)
Type: Domain

Glucose-6-phosphate dehydrogenase (

) (G6PDH) is a ubiquitous protein, present in bacteria and all eukaryotic cell types . The enzyme catalyses the the first step in the pentose pathway, i.e. the conversion of glucose-6-phosphate to gluconolactone 6-phosphate in the presence of NADP, producing NADPH. The ubiquitous expression of the enzyme gives it a major role in the production of NADPH for the many NADPH-mediated reductive processes in all cells, and is critical for NADPH homeostasis and redox regulation . Deficiency of G6PDH is a common genetic abnormality affecting millions of people worldwide. Many sequence variants, most caused by single point mutations, are known, exhibiting a wide variety of phenotypes with the distinctive one being chronic and drug- or food-induced hemolytic anemia, attributed to the inability to produce NADPH and withstand harmful oxidants in erythrocyte cells .

This entry represents the NAD-binding domain of glucose-6-phosphate dehydrogenase.
Glucose-6-phosphate dehydrogenase, C-terminal (G6P_DH_C)
Type: Domain

Glucose-6-phosphate dehydrogenase (

) (G6PDH) is a ubiquitous protein, present in bacteria and all eukaryotic cell types . The enzyme catalyses the the first step in the pentose pathway, i.e. the conversion of glucose-6-phosphate to gluconolactone 6-phosphate in the presence of NADP, producing NADPH. The ubiquitous expression of the enzyme gives it a major role in the production of NADPH for the many NADPH-mediated reductive processes in all cells, and is critical for NADPH homeostasis and redox regulation . Deficiency of G6PDH is a common genetic abnormality affecting millions of people worldwide. Many sequence variants, most caused by single point mutations, are known, exhibiting a wide variety of phenotypes with the distinctive one being chronic and drug- or food-induced hemolytic anemia, attributed to the inability to produce NADPH and withstand harmful oxidants in erythrocyte cells .

This entry represents the C-terminal domain of glucose-6-phosphate dehydrogenase.
Glycylpeptide N-tetradecanoyltransferase, N-terminal (NMT_N)
Type: Domain

Glycylpeptide N-tetradecanoyltransferase, also known as Myristoyl-CoA:protein N-myristoyltransferase (

) (Nmt), is the enzyme responsible for transferring a myristate group on the N-terminal glycine of a number of cellular eukaryotics and viral proteins . Nmt is a monomeric protein of about 50 to 60kDa whose sequence appears to be well conserved. In Drosophila, this protein is critical for the developmental processes that involve cell shape changes and movement .

The N and C-terminal domains of NMT are structurally similar, each adopting an acyl-CoA N-acyltransferase-like fold. This entry represents the N-terminal region .
Glycylpeptide N-tetradecanoyltransferase, C-terminal (NMT_C)
Type: Domain

Glycylpeptide N-tetradecanoyltransferase, also known as Myristoyl-CoA:protein N-myristoyltransferase (

) (Nmt), is the enzyme responsible for transferring a myristate group on the N-terminal glycine of a number of cellular eukaryotics and viral proteins . Nmt is a monomeric protein of about 50 to 60kDa whose sequence appears to be well conserved. In Drosophila, this protein is critical for the developmental processes that involve cell shape changes and movement .

The N and C-terminal domains of NMT are structurally similar, each adopting an acyl-CoA N-acyltransferase-like fold. This entry represents the C-terminal region .
Glycylpeptide N-tetradecanoyltransferase, conserved site (NMT_CS)
Type: Conserved_site

Glycylpeptide N-tetradecanoyltransferase, also known as Myristoyl-CoA:protein N-myristoyltransferase (

) (Nmt), is the enzyme responsible for transferring a myristate group on the N-terminal glycine of a number of cellular eukaryotics and viral proteins . Nmt is a monomeric protein of about 50 to 60kDa whose sequence appears to be well conserved. In Drosophila, this protein is critical for the developmental processes that involve cell shape changes and movement .

Two highly conserved regions are found. The first one is located in the central section, the second in the C-terminal part.
Methyl-coenzyme M reductase, beta subunit, C-terminal (Me_CoM_Rdtase_bsu_C)
Type: Domain

Methyl-coenzyme M reductase (MCR) catalyses the reduction of methyl-coenzyme M (CH3-SCoM) and coenzyme B (HS-CoB) to methane and the corresponding heterosulphide CoM-S-S-CoB (

), the final step in methane biosynthesis. This reaction proceeds under anaerobic conditions by methanogenic Archaea , and requires a nickel-porphinoid prosthetic group, coenzyme F430, which is in the EPR-detectable Ni(I) oxidation state in the active enzyme. Studies on a catalytically inactive enzyme aerobically co-crystallized with coenzyme M displayed a fully occupied coenzyme M-binding site with no alternate conformations. The binding of coenzyme M appears to induce specific conformational changes that suggests a molecular mechanism by which the enzyme ensures that methyl-coenzyme M enters the substrate channel prior to coenzyme B, as required by the active-site geometry .

MCR is a hexamer composed of 2 alpha, 2 beta, and 2 gamma subunits with two identical nickel porphinoid active sites, which form two long active site channels with F430 embedded at the bottom .

This entry represents the C-terminal domain from the beta subunit of methyl-conenzyme M reductase (MCR). The C-terminal domain of MCR beta has an all-α fold with buried central helix. This entry is found in assocation with

.
Methyl-coenzyme M reductase, beta subunit, N-terminal (Me_CoM_Rdtase_bsu_N)
Type: Domain

This entry represents the N-terminal domain from the beta subunit of methyl-conenzyme M reductase (MCR). The N-terminal domain has an α/β ferredoxin-like fold. This entry is found in assocation with

.

Methyl-coenzyme M reductase (MCR) catalyses the reduction of methyl-coenzyme M (CH3-SCoM) and coenzyme B (HS-CoB) to methane and the corresponding heterosulphide CoM-S-S-CoB (

), the final step in methane biosynthesis. This reaction proceeds under anaerobic conditions by methanogenic Archaea , and requires a nickel-porphinoid prosthetic group, coenzyme F430, which is in the EPR-detectable Ni(I) oxidation state in the active enzyme. Studies on a catalytically inactive enzyme aerobically co-crystallized with coenzyme M displayed a fully occupied coenzyme M-binding site with no alternate conformations. The binding of coenzyme M appears to induce specific conformational changes that suggests a molecular mechanism by which the enzyme ensures that methyl-coenzyme M enters the substrate channel prior to coenzyme B, as required by the active-site geometry .

MCR is a hexamer composed of 2 alpha, 2 beta, and 2 gamma subunits with two identical nickel porphinoid active sites, which form two long active site channels with F430 embedded at the bottom .
Peptidase C2, calpain family (Calpain_cysteine_protease)
Type: Family

This group of cysteine peptidases belong to the MEROPS peptidase family C2 (calpain family, clan CA). A type example is calpain, which is an intracellular protease involved in many important cellular functions that are regulated by calcium . The protein is a complex of 2 polypeptide chains (light and heavy), with eleven known active peptidases in humans and two non-peptidase homologues known as calpamodulin and androglobin . These include a highly calcium-sensitive (i.e., micro-molar range) form known as mu-calpain, mu-CANP or calpain I; a form sensitive to calcium in the milli-molar range, known as m-calpain, m-CANP or calpain II; and a third form, known as p94, which is found in skeletal muscle only .

All forms have identical light but different heavy chains. Both mu- and m-calpain are heterodimers containing an identical 28kDa subunit and an 80kDa subunit that shares 55-65% sequence homology between the two proteases . The crystallographic structure of m-calpain reveals six "domains" in the 80kDa subunit :

A 19-amino acid NH2-terminal sequence;

Active site domain IIa;

Active site domain IIb. Domain 2 shows
low levels of sequence similarity to papain; although the catalytic His has
not been located by biochemical means, it is likely that calpain and papain
are related .

Domain III;

An 18-amino acid extended sequence linking domain III to domain IV;

Domain IV, which resembles the penta EF-hand family of polypeptides, binds calcium and regulates activity . Ca
2+
-binding causes a rearrangement of the protein backbone, the net effect of which is that a Trp side chain, which acts as a wedge between catalytic domains IIa and IIb in the apo state, moves away from the active site cleft allowing for the proper formation of the catalytic triad .

Calpain-like mRNAs have been identified in other organisms including bacteria, but the molecules encoded by these mRNAs have not been isolated, so little is known about their properties. How calpain activity is regulated in these organisms cells is still unclear In metazoans, the activity of calpain is controlled by a single proteinase inhibitor, calpastatin (

). The calpastatin gene can produce eight or more calpastatin polypeptides ranging from 17 to 85kDa by use of different promoters and alternative splicing events. The physiological significance of these different calpastatins is unclear, although all bind to three different places on the calpain molecule; binding to at least two of the sites is Ca2+ dependent. The calpains ostensibly participate in a variety of cellular processes including remodelling of cytoskeletal/membrane attachments, different signal transduction pathways, and apoptosis. Deregulated calpain activity following loss of Ca2+ homeostasis results in tissue damage in response to events such as myocardial infarcts, stroke, and brain trauma .
Replication-associated protein G2P, N-terminal (G2P_N)
Type: Domain

The entry represents the N-terminal domain found in gene II protein (G2P) from Enterobacteria phage M13 and similar proteins from bacteriophages and bacterial prophages. A much shorter protein of unknown function, translated from a conserved in-frame alternative initiator, is designated gene X protein (G10P). Proteins containing this domain are involved in viral DNA replication.
DTXR-type HTH domain (HTH_DTXR)
Type: Domain

The DtxR-type HTH domain is a DNA-binding, winged helix-turn-helix (wHTH) domain of about 65 residues present in metalloregulators of the DtxR/MntR family. The family is named after Corynebacterium diphtheriae DtxR, an iron-specific diphtheria toxin repressor, and Bacillus subtilis MntR, a manganese transport regulator. Iron-responsive metalloregulators such as DtxR and IdeR occur in Gram-positive bacteria of the high GC branch, while manganese-responsive metalloregulators like MntR are described in diverse genera of Gram-positive and Gram-negative bacteria and also in Archaea .The metalloregulators like DtxR/MntR contain the DNA-binding DtxR-type HTH domain usually in the N-terminal part. The C-terminal part contains a dimerisation domain with two metal-binding sites, although the primary metal-binding site is less conserved in the Mn(II)-regulators. Fe(II)-regulated proteins contain an SH3-like domain as a C-terminal extension, which is absent in Mn(II)-regulated MntR .

Metal-ion dependent regulators orchestrate the virulence of several important human pathogens. The DtxR protein regulates the expression of diphtheria toxinin response to environmental iron concentrations. Furthermore, DtxR and IdeR control iron uptake . Homeostasis of manganese, which is an essential nutrient, is regulated by MntR. A typical DtxR-type metalloregulator binds two divalent metal effectors per monomer, upon which allosteric changes occur that moderate binding to the cognate DNA operators. Iron-bound DtxR homodimers bind to an interrupted palindrome of 19 bp, protecting a sequence of ~30 bp. The crystal structures of iron-regulated and manganese-regulated repressors show that the DNA binding domain contains three α-helices and a pair of antiparallel β-strands. Helices 2 and 3 comprise the helix-turn-helix motif and the β-strands are called the wing . This wHTH topology is similar to the lysR-type HTH (see

). Most DtxR-type metalloregulators bind as dimers to the DNA major groove.
Replication-associated protein G2P, C-terminal (G2P_C)
Type: Domain

The entry represents the C-terminal domain found in gene II protein (G2P) from bacteriophage. A much shorter protein of unknown function, translated from a conserved in-frame alternative initiator, is designated gene X protein (G10P). Proteins containing this domain are involved in viral DNA replication. This domain roughly covers the G10P region.