This domain consists of several eukaryotic suppressor of forked (Suf) like proteins. The Drosophila melanogaster suppressor of forked [Su(f)] protein shares homology with the Saccharomyces cerevisiae RNA14 protein and the 77kDa subunit of Homo sapiens cleavage stimulation factor, which are proteins involved in mRNA 3' end formation. This suggests a role for Su(f) in mRNA 3' end formation in Drosophila. The su(f) gene produces three transcripts; two of them are polyadenylated at the end of the transcription unit, and one is a truncated transcript, polyadenylated in intron 4. It is thought that su(f) plays a role in the regulation of poly(A) site utilisation and the GU-rich sequence is important for this regulation to occur [].
The HAT (Half A TPR) repeat has a repetitive pattern characterised by three aromatic residues with a conserved spacing. They are structurally and sequentially similar to TPRs (tetratricopeptide repeats), though they lack the highly conserved alanine and glycine residues found in TPRs. The number of HAT repeats found in different proteins varies between 9 and 12. HAT-repeat-containing proteins appear to be components of macromolecular complexes that are required for RNA processing [
]. The HAT motif has striking structural similarities to HEAT repeats (), being of a similar length and consisting of two short helices connected by a loop domain, as in HEAT repeats. Some studies have suggested that the HAT repeats may be involved in protein-protein interactions [
,
]. However, the HAT repeats of Arabidopsis HCF107 protein have been shown to bind RNA []. Proteins containing this domain includes:Crooked neck (Crn) from Drosophila. It associates with the RNA-binding protein HOW to control glial cell maturation [
]. Clf1, Prp6 and Prp39 from S. cerevisiae. Clf1 is part of the of the NineTeen Complex (NTC) that stabilises U6 snRNA in catalytic forms of the spliceosome containing U2, U5, and U6 snRNAs [
,
]. Prp6 and Prp39 are involved in pre-mRNA splicing.Cleavage stimulation factor subunit 3 (CSTF3 or CstF-77) and crooked neck-like protein 1 (CRNKL1) from mammals. CSTF3 is required for polyadenylation and 3'-end cleavage of mammalian pre-mRNAs [
]. Protein high chlorophyll fluorescent 107 (HCF107) from Arabidopsis. HCF107 exhibits sequence-specific RNA binding and RNA remodeling activities, probably leading to the activation of translation of the target gene cluster psbB-psbT-psbH-petB-petD [
]. It blocks 5'-3' and 3'-5' exoribonucleases (e.g. polynucleotide phosphorylase (PNPase), RNase R) in vitro []. It is necessary for intercistronic RNA processing of the psbH 5' untranslated region or the stabilization of 5' processed psbH RNAs and is also required for the synthesis of psbB [,
,
].
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 [
,
].Ribosomal protein L26 is one of the proteins from the large ribosomal subunit. In their mature form, these proteins have 103 to 150 amino-acid residues. Eukaryotic L26 is a conserved protein that shares notable sequence and structure identity with archaeal and eubacterial L24. This entry represents the archaeal L24 and eukaryotic branch of these proteins.
The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases. These enzymes catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. A classification of glycosyltransferases using nucleotide diphospho-sugar, nucleotide monophospho-sugar and sugar phosphates ([intenz:2.4.1.-]) and related proteins into distinct sequence based families has been described []. This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. The same three-dimensional fold is expected to occur within each of the families. Because 3-D structures are better conserved than sequences, several of the families defined on the basis of sequence similarities may have similar 3-D structures and therefore form 'clans'.Alpha-1,3-mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase (GNT-I, GLCNAC-T I)
transfers N-acetyl-D-glucosamine from UDP to high-mannose glycoprotein N-oligosaccharide. This is an essential step in the synthesis of complex or hybrid-type N-linked oligosaccharides. The enzyme is an integral membrane protein localized to the Golgi apparatus, and is probably distributed in all tissues [
]. Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1 (POMGNTI, GNT-I.2) participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins [,
,
]. These proteins are members of the glycosyl transferase family 13 ()
This plant-specific family of proteins are defined by an uncharacterised region 57 residues in length. It is found toward the N terminus of most proteins that contain it. Examples include at least several proteins from Arabidopsis thaliana (Mouse-ear cress) and Oryza sativa (Rice). The function of the proteins are unknown.
Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product.PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane [
,
,
]. Within the core of the complex, the chlorophyll and beta-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecularweight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection [
]. In PSII, the oxygen-evolving complex (OEC) is responsible for catalysing the splitting of water to O(2) and 4H+. The OEC is composed of a cluster of manganese, calcium and chloride ions bound to extrinsic proteins. In cyanobacteria there are five extrinsic proteins in OEC (PsbO, PsbP-like, PsbQ-like, PsbU and PsbV), while in plants there are only three (PsbO, PsbP and PsbQ), PsbU and PsbV having been lost during the evolution of green plants [
].This entry represents the C-terminal domain found in PSII OEC protein PsbP. Both PsbP and PsbQ (
) are regulators that are necessary for the biogenesis of optically active PSII. PsbP increases the affinity of the water oxidation site for chloride ions and provides the conditions required for high affinity binding of calcium ions [
,
]. The crystal structure of PsbP from Nicotiana tabacum (Common tobacco) revealed a two-domain structure, where domain 1 may play a role in the ion retention activity in PSII, the N-terminal residues being essential for calcium and chloride ion retention activity []. PsbP is encoded in the nuclear genome in plants.
This entry represents a structural domain consisting of a 3-layer α/β/α fold. The β layer is composed of seven β-sheets, and the overall order is: (β-hairpin)-β(3)-α-β(4)-α. Domains with this structure are found in the following protein families:Ran-binding protein Mog1, which interacts with Ran GTPase to stimulate guanine nucleotide release, suggesting Mog1 regulates the nuclear transport functions of Ran [
,
].The photosystem II (PSII) oxygen-evolving complex protein PsbP, which is a regulator necessary for the biogenesis of optically active PSII. PsbP increases the affinity of the water oxidation site for chloride ions and provides the conditions required for high affinity binding of calcium ions [
].
The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [
].This entry represents the methionyl and leucyl tRNA synthetases, which are class I aminoacyl-tRNA synthetases.
The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [].Methionine-tRNA ligase (
) is an alpha 2 dimer. In some species (archaea, eubacteria and eukaryotes) a coding sequence, similar to the C-terminal end of MetRS, is present as an independent gene which is a tRNA binding domain as a dimer. In eubacteria, MetRS can also be split in two sub-classes corresponding to the presence of one or two CXXC domains specific to zinc binding. The crystal structures of a number of methionine-tRNA ligases are known [
,
,
].
The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases. These enzymes catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. A classification of glycosyltransferases using nucleotide diphospho-sugar, nucleotide monophospho-sugar and sugar phosphates ([intenz:2.4.1.-]) and related proteins into distinct sequence based families has been described []. This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. The same three-dimensional fold is expected to occur within each of the families. Because 3-D structures are better conserved than sequences, several of the families defined on the basis of sequence similarities may have similar 3-D structures and therefore form 'clans'.Glycosyltransferase family 35
comprises enzymes with only one known activity; glycogen and starch phosphorylase ().
The main role of glycogen phosphorylase (GPase) is to provide phosphorylated glucose molecules (G-1-P) [
]. GPase is a highly regulated allosteric enzyme. The net effect of the regulatory site allows the enzyme to operate at a variety of rates; the enzyme is not simply regulated as "on"or "off", but rather it can be thought of being set to operate at an ideal rate based on changing conditions at in the cell. The most important allosteric effector is the phosphate molecule covalently attached to Ser14.
This switches GPase from the b (inactive) state to the a (active) state. Upon phosphorylation, GPase attains about 80% of its Vmax. When the enzyme is not phosphorylated, GPase activity is practically non-existent at low AMP levels.There is some apparent controversy as to the structure of GPase. All sources agree that the enzyme is multimeric, but there is apparent controversy as to the enzyme being a tetramer or a dimer. Apparently, GPase (in the aform) forms tetramers in the crystal form. The consensus seems to be that `regardless of the a or b form, GPase functions as a dimer
in vivo[
]. The GPase monomer is best described as consisting of two domains, an N-terminal domain and a C-terminal domain []. The C-terminal domain is often referred to as the catalytic domain. It consists of a β-sheet core surrounded by layers of helical segments []. The vitamin cofactor pyridoxal phosphate (PLP) is covalently attached to the amino acid backbone. The N-terminal domain also consists of a central β-sheet core and is surrounded by layers of helical segments. The N-terminal domain contains different allosteric effector sites to regulate the enzyme.Bacterial phosphorylases follow the same catalytic mechanisms as their plant and animal counterparts, but differ considerably in terms of their substrate specificity and regulation. The catalytic domains are highly conserved while the regulatory sites are only poorly conserved. For maltodextrin phosphorylase from Escherichia coli the physiological role of the enzyme in the utilisation of maltidextrins is known in detail; that of all the other bacterial phosphorylases is still unclear. Roles in regulatuon of endogenous glycogen metabolism in periods of starvation, and sporulation, stress response or quick adaptation to changing environments are possible [
].
Elongator complex protein 1 (also known as Iki3) is a component of the RNA polymerase II elongator complex, which is a major histone acetyltransferase component of the RNA polymerase II (RNAPII) holoenzyme. The eukaryotic elongator complex has been associated with many cellular activities, including transcriptional elongation [
,
], but its main function is tRNA modification [,
]. It is required for the formation of 5-methoxy-carbonylmethyl (mcm5) and 5-carbamoylmethyl (ncm5) groups on uridine nucleosides present at the wobble position of many tRNAs [].
Chalcone isomerase (
; also known as chalcone-flavanone isomerase) is a plant enzyme responsible for the isomerisation of chalcone to naringenin, a key step in the biosynthesis of flavonoids. The Petunia hybrida (Petunia) genome contains two genes coding for very similar enzymes, ChiA and ChiB, but only the first seems to encode a functional chalcone isomerase. Chalcone isomerase has a core 2-layer alpha/beta structure consisting of beta(3)-alpha(2)-beta-alpha(2)-beta(3) [
].This entry represents chalcone isomerases and enzymes with a common structure.
Chalcone isomerase (
; also known as chalcone-flavanone isomerase or fatty-acid-binding protein) is a plant enzyme responsible for the isomerisation of chalcone to naringenin, a key step in the biosynthesis of flavonoids. The Petunia hybrida (Petunia) genome contains two genes coding for very similar enzymes, ChiA and ChiB, but only the first seems to encode a functional chalcone isomerase. This entry represents a 3-layer beta/beta/alpha sandwich subdomain found in chalcone isomerases [
].
Small nuclear ribonucleoprotein Prp3, C-terminal domain
Type:
Domain
Description:
This domain is found at the C-terminal end of U4/U6 and U4/U5/U6-small nuclear ribonucleoprotein Prp3, part of the tri-RNA complex
that form the spliceosome. Prp3 plays a key role in the recognition
of the snRNA duplex. This binding domain, highly conserved amongeukaryotes, interacts with the 3' end of U6 snRNA. It adopts a
ferredoxin-like fold, showing a five-stranded mixed β-sheet withthree α-helices, two of them running parallel to the β-strands
on one side of the sheet and one on the other. This fold is extendedwith a long β-hairpin, an extra β-strand, an helix and a final
loop at the C terminus [,
,
,
].
Prp3 (also known as PRP3) participates in pre-mRNA splicing [
]. It may play a role in the assembly of the U4/U5/U6 tri-snRNP complex []. Defects in PRPF3 are the cause of retinitis pigmentosa type 18 (RP18). RP leads to degeneration of retinal photoreceptor cells [,
,
]. In Arabidposis thaliana, protein RDM16 acts as a pre-mRNA splicing factor and functions in RNA-directed DNA methylation by influencing Pol V transcript levels [
].
Cleavage/polyadenylation specificity factor, A subunit, C-terminal
Type:
Domain
Description:
This family includes a region that lies towards the C terminus of the cleavage and polyadenylation specificity factor (CPSF) A (160kDa)
subunit. CPSF is involved in mRNA polyadenylation and binds the AAUAAA conserved sequence in pre-mRNA. CPSF has also beenfound to be necessary for splicing of single-intron pre-mRNAs [
]. The function of the aligned region is unknown but may be involvedin RNA/DNA binding.
Riboflavin is converted into catalytically active cofactors (FAD and FMN) by the actions of riboflavin kinase (
), which converts it into FMN, and FAD synthetase (
), which adenylates FMN to FAD. Eukaryotes usually have two separate enzymes, while most prokaryotes have a single bifunctional protein that can carry out both catalyses, although exceptions occur in both cases. While eukaryotic monofunctional riboflavin kinase is orthologous to the bifunctional prokaryotic enzyme [
], the monofunctional FAD synthetase differs from its prokaryotic counterpart, and is instead related to the PAPS-reductase family []. The bacterial FAD synthetase that is part of the bifunctional enzyme has remote similarity to nucleotidyl transferases and, hence, it may be involved in the adenylylation reaction of FAD synthetases [].This entry represents prokaryotic-type FAD synthetase, which occurs primarily as part of a bifunctional enzyme.
The majority of molybdenum-containing enzymes utilise a molybdenum cofactor (MoCF or Moco) consisting of a Mo atom coordinated via a cis-dithiolene moiety to molybdopterin (MPT). MoCF is ubiquitous in nature, and the pathway for MoCF biosynthesis is conserved in all three domains of life. MoCF-containing enzymes function as oxidoreductases in carbon, nitrogen, and sulphur metabolism [
,
]. In Escherichia coli, biosynthesis of MoCF is a three stage process. It begins with the MoaA and MoaC conversion of GTP to the meta-stable pterin intermediate precursor Z. The second stage involves MPT synthase (MoaD and MoaE), which converts precursor Z to MPT; MoeB is involved in the recycling of MPT synthase. The final step in MoCF synthesis is the attachment of mononuclear Mo to MPT, a process that requires MoeA and which is enhanced by MogA in an Mg2 ATP-dependent manner []. MoCF is the active co-factor in eukaryotic and some prokaryotic molybdo-enzymes, but the majority of bacterial enzymes requiring MoCF, need a modification of MTP for it to be active; MobA is involved in the attachment of a nucleotide monophosphate to MPT resulting in the MGD co-factor, the active co-factor for most prokaryotic molybdo-enzymes. Bacterial two-hybrid studies have revealed the close interactions between MoeA, MogA, and MobA in the synthesis of MoCF []. Moreover the close functional association of MoeA and MogA in the synthesis of MoCF is supported by fact that the known eukaryotic homologues to MoeA and MogA exist as fusion proteins: CNX1 () of Arabidopsis thaliana (Mouse-ear cress), mammalian Gephryin (e.g.
) and Drosophila melanogaster (Fruit fly) Cinnamon (
) [
].This entry contains the molybdenum cofactor biosynthesis protein MoaC, also known as cyclic pyranopterin monophosphate synthase.
Molybdopterin cofactor biosynthesis C (MoaC) domain
Type:
Domain
Description:
The majority of molybdenum-containing enzymes utilise a molybdenum cofactor (MoCF or Moco) consisting of a Mo atom coordinated via a cis-dithiolene moiety to molybdopterin (MPT). MoCF is ubiquitous in nature, and the pathway for MoCF biosynthesis is conserved in all three domains of life. MoCF-containing enzymes function as oxidoreductases in carbon, nitrogen, and sulphur metabolism [
,
]. In Escherichia coli, biosynthesis of MoCF is a three stage process. It begins with the MoaA and MoaC conversion of GTP to the meta-stable pterin intermediate precursor Z. The second stage involves MPT synthase (MoaD and MoaE), which converts precursor Z to MPT; MoeB is involved in the recycling of MPT synthase. The final step in MoCF synthesis is the attachment of mononuclear Mo to MPT, a process that requires MoeA and which is enhanced by MogA in an Mg2 ATP-dependent manner [
]. MoCF is the active co-factor in eukaryotic and some prokaryotic molybdo-enzymes, but the majority of bacterial enzymes requiring MoCF, need a modification of MTP for it to be active; MobA is involved in the attachment of a nucleotide monophosphate to MPT resulting in the MGD co-factor, the active co-factor for most prokaryotic molybdo-enzymes. Bacterial two-hybrid studies have revealed the close interactions between MoeA, MogA, and MobA in the synthesis of MoCF []. Moreover the close functional association of MoeA and MogA in the synthesis of MoCF is supported by fact that the known eukaryotic homologues to MoeA and MogA exist as fusion proteins: CNX1 () of Arabidopsis thaliana (Mouse-ear cress), mammalian Gephryin (e.g.
) and Drosophila melanogaster (Fruit fly) Cinnamon (
) [
].This entry contains the molybdenum cofactor biosynthesis protein MoaC, also known as cyclic pyranopterin monophosphate synthase.
This entry represents the enzyme protein dihydroorotate dehydrogenase (also called quinone) exclusively for class 2. It includes members from bacteria, yeast, plants etc. The subfamilies 1 and 2 share extensive homology, particularly toward the C terminus. This subfamily has a longer N-terminal region.Dihydroorotate dehydrogenase (DHOD), also known as dihydroorotate oxidase, catalyses the fourth step in de novo pyrimidine biosynthesis, the stereospecific oxidation of (S)-dihydroorotate to orotate, which is the only redox reaction in this pathway. DHODs can be divided into two mains classes: class 1 cytosolic enzymes found primarily in Gram-positive bacteria, and class 2 membrane-associated enzymes found primarily in eukaryotic mitochondria and Gram-negative bacteria [
].The class 1 DHODs can be further divided into subclasses 1A and 1B, which differ in their structural organisation and use of electron acceptors. The 1A enzyme is a homodimer of two PyrD subunits where each subunit forms a TIM barrel fold with a bound FMN cofactor located near the top of the barrel [
]. Fumarate is the natural electron acceptor for this enzyme. The 1B enzyme, in contrast is a heterotetramer composed of a central, FMN-containing, PyrD homodimer resembling the 1A homodimer, and two additional PyrK subunits which contain FAD and a 2Fe-2S cluster []. These additional groups allow the enzyme to use NAD(+) as its natural electron acceptor.The class 2 membrane-associated enzymes are monomers which have the FMN-containing TIM barrel domain found in the class 1 PyrD subunit, and an additional N-terminal alpha helical domain [
,
]. These enzymes use respiratory quinones as the physiological electron acceptor.
Dihydroorotate dehydrogenase (
) (DHOdehase) catalyses the fourth step in the
de novobiosynthesis of pyrimidine, the conversion of dihydroorotate into orotate. DHOdehase is a ubiquitous FAD flavoprotein. In bacteria (gene pyrD), DHOdease is located on the inner side of the cytosolic membrane. In some yeasts, such as in Saccharomyces cerevisiae (gene URA1), it is a cytosolic protein while in other eukaryotes it is found in the mitochondria [
].
The ribosomal RNA large subunit methyltransferase E (
) methylates the 23S rRNA. It specifically methylates the uridine in position 2552 of 23s rRNA in the 50S particle using S-adenosyl-L-methionine as a substrate [
]. It was previously known as cell division protein FtsJ.This entry represents the ribosomal RNA large subunit methyltransferase E family, which also includes tRNA (uridine-2'-O-)-methyltransferases. This enzyme methylates the 2'-O-ribose of nucleotides at positions 32 and 34 of the tRNA anticodon loop [
].
This entry represents FtsJ domain, which is found in proteins that methylate RNA, including Ribosomal RNA large subunit methyltransferase E (formerly known as RrmJ or FtsJ). RrmJ is a well conserved heat shock protein with close homologs in prokaryotes, archaea, and eukaryotes. RrmJ is responsible for methylating 23 S rRNA at position U2552 in the aminoacyl (A)1-site of the ribosome [
,
,
]. U2552 is one of the five universally conserved A-loop residues and has been shown to be methylated at the ribose 2'-OH group in the majority of organisms investigated so far. This suggests that this modification plays an important role in the A-loop function. RrmJ recognises its methylation target only when the 23 S rRNA is present in 50 S ribosomal subunits. This suggests that the RrmJ-mediated methylation must occur late in the maturation process of the ribosome. This is in contrast to other known 23 S rRNA modifications that occur in earlier maturation steps.The 1.5 A crystal structure of RrmJ in complex with its cofactor S-adenosylmethionine revealed that RrmJ has a methyltransferase fold. The active site of RrmJ appears to be formed by a catalytic triad consisting of two lysine residues and the negatively charged aspartate residue. Another highly conserved glutamate residue that is present in the active site of RrmJ appears to play only a minor role in the methyltransfer reaction in vivo [
]. This domain is also found in enzymes that methylate other positions in the 23S rRNA such as Ribosomal RNA large subunit methyltransferase M, 23S rRNA (cytidine-2'-O)-methyltransferase TlyA [
], and mRNA, like Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase 1 [].
This entry represents E2F binding proteins. E2F transcription factors play an essential role in cell proliferation and apoptosis and their activity is frequently deregulated in human cancers. E2F activity is regulated by a variety of mechanisms, frequently mediated by proteins binding to individual members or a subgroup of the family. E2F-associated phosphoprotein (EAPP)interacts with a subset of E2F factors and influences E2F-dependent promoter activity. EAPP is present throughout the cell cycle but disappears during mitosis [
].
This family contains several plant dormancy-associated and auxin-repressed proteins [
]. The expression of the DRM/ARP family members may be regulated by stress and environmental factors [].
Eukaryotic translation initiation factor 3 subunit D
Type:
Family
Description:
Eukaryotic translation initiation factor 3 subunit D (eIF3d) is a component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome [,
]. The gene coding for the protein has been implicated in cancer in mammals [].
Nuclear speckle splicing regulatory protein 1, N-terminal
Type:
Domain
Description:
This domain is found at the N-terminal of Nuclear speckle splicing regulatory protein 1 (NRP1, also known as Nuclear speckle-related protein 70 and Coiled-coil domain-containing protein 55) and contains a coiled-coil domain that plays a critical role in NRP1 alternative splicing activity and self-oligomerization. NRP1 is a RNA-binding protein that mediates pre-mRNA alternative splicing regulation [
,
].
This entry represents the calcium-binding domain found in SPARC (Secreted Protein Acidic and Rich in Cysteine) and Testican (also known as SPOCK; or SParc/Osteonectin, Cwcv and Kazal-like domains) proteins. SPARC proteins are down-regulated in various tumours and may have a tumour-suppressor function [
,
]. Testican-3 appears to be a novel regulator that reduces the activity of matrix metalloproteinase (MMP) in adult T-cell leukemia (ATL) [].This cysteine-rich domain is responsible for the anti-spreading activity of human urothelial cells. This extracellular calcium-binding domain is rich in α-helices and contains two EF-hands that each coordinates one Ca2+ ion, forming a helix-loop-helix structure that not only drives the conformation of the protein but is also necessary for biological activity. The anti-spreading activity was dependent on the coordination of Ca2+ by a Glu residue at the Z position of EF-hand 2 [
].
This family consists of glycine rich proteins, including Arabidopsis AtGRP3 (At2g05520). AtGRP3 interacts with the receptor-like kinase AtWAK1 and functions in root size determination during development and in Aluminum stress [
].
The PHO-4 family of transporters includes the phosphate-repressible phosphate permease (PHO-4) from Neurospora crassa, which is probably a sodium-phosphate symporter [
] and the Low-affinity inorganic phosphate transporter PitA from Escherichia coli, whose activity impacts bacterial growth in low Mg2+ conditions [,
]. This family also includes the human leukemia virus receptor [,
].
In eukaryotes, glutathione S-transferases (GSTs) participate in the detoxification of reactive electrophilic compounds by catalysing their
conjugation to glutathione. The GST domain is also found in S-crystallins from squid, and proteins with no known GST activity, such as eukaryotic elongation factors 1-gamma and the HSP26 family of stress-related proteins, which include auxin-regulated proteins in plants and stringent starvation proteins in Escherichia coli. The major lens polypeptide of cephalopods is also a GST [,
,
,
].Bacterial GSTs of known function often have a specific, growth-supporting role in biodegradative metabolism: epoxide ring opening and tetrachlorohydroquinone reductive dehalogenation are two examples of the reactions catalysed by these bacterial GSTs. Some regulatory proteins, like the stringent starvation proteins, also belong to the GST family [
,
]. GST seems to be absent from Archaea in which gamma-glutamylcysteine substitute to glutathione as major thiol.Glutathione S-transferases form homodimers, but in eukaryotes can also form heterodimers of the A1 and A2 or YC1 and YC2 subunits. The homodimeric enzymes display a conserved structural fold. Each monomer is composed of a distinct N-terminal sub-domain, which adopts the thioredoxin fold, and a C-terminal all-helical sub-domain. This entry is the C-terminal domain.
Zeste white 10 (ZW10) was initially identified as a mitotic checkpoint protein involved in chromosome segregation, and then implicated in targeting cytoplasmic dynein and dynactin to mitotic kinetochores, but it is also important in non-dividing cells. These include cytoplasmic dynein targeting to Golgi and other membranes, and SNARE-mediated ER-Golgi trafficking [
,
,
]. Dominant-negative ZW10, anti-ZW10 antibody, and ZW10 RNA interference (RNAi) cause Golgi dispersal. ZW10 RNAi also disperse endosomes and lysosomes [].Drosophila kinetochore components Rough deal (Rod) and Zw10 are required for the proper functioning of the metaphase checkpoint in flies and mammals [
,
]. The eukaryotic spindle assembly checkpoint (SAC) monitors microtubule attachment to kinetochores and prevents anaphase onset until all kinetochores are aligned on the metaphase plate. It is an essential surveillance mechanism that ensures high fidelity chromosome segregation during mitosis. In higher eukaryotes, cytoplasmic dynein is involved in silencing the SAC by removing the checkpoint proteins Mad2 and the Rod-Zw10-Zwilch complex (RZZ) from aligned kinetochores [,
,
].
This is a domain of eukaryotic protein disulphide isomerases, generally found
in two copies. The domain is similar to thioredoxin but the redox-active disulphide region motif is APWCGHCK.
The proteasome (or macropain) (
) [
,
,
,
,
] is a multicatalytic proteinase complex in eukaryotes and archaea, and in some bacteria, that seems to be involved in an ATP/ubiquitin-dependent nonlysosomal proteolytic pathway. In eukaryotes the proteasome is composed of 28 distinct subunits which form a highly ordered ring-shaped structure (20S ring) of about 700kDa. Most proteasome subunits can be classified, on the basis on sequence similarities into two groups, alpha (A) and beta (B). These are arranged in four rings of seven proteins, consisting of a ring of alpha subunits, two rings of beta subunits, and a ring of alpha subunits. In eukaryotes, each alpha and each beta ring consists of different proteins. Three of the beta subunits are peptidases in subfamily T1A, and each has a distinctive specificity (trypsin-like, chymotrypsin-like and glutamyl peptidase-like). The peptidases are N-terminal nucleophile hydrolases in which the N-terminal threonine is the nucleophile in the hydrolytic reaction []. In the immunoproteasome, the catalytic components are replaced by three specialist, catalytic beta subunits []. In bacteria and archaea there is only one alpha subunit and one beta subunit, and each ring is a homoseptamer.This entry represents a conserved sequence region found in the N-terminal region of these proteins.
Mechanosensitive ion channel MscS-like, plants/fungi
Type:
Family
Description:
This entry represents a group of MscS-like (mechanosensitive channels of small conductance-like) proteins found in fungi and plants. Ten MscS-Like (MSL) proteins have been found in the genome of Arabidopsis thaliana [
,
]. In the fission yeast Schizosaccharomyces pombethe mechanosensitive ion channel proteins are known as Msy1 and Msy2 [
].Mechanosensitive (MS) channels provide protection against hypo-osmotic shock, responding both to stretching of the cell membrane and to membrane depolarisation. They are present in the membranes of organisms from the three domains of life: bacteria, archaea, and eukarya [
]. There are two families of MS channels: large-conductance MS channels (MscL) and small-conductance MS channels (MscS or YGGB). The pressure threshold for MscS opening is 50% that of MscL []. The MscS family is much larger and more variable in size and sequence than the MscL family. Much of the diversity in MscS proteins occurs in the size of the transmembrane regions, which ranges from three to eleven transmembrane helices, although the three C-terminal helices are conserved.In the fission yeast
Schizosaccharomyces pombethe mechanosensitive ion channel proteins are known as Msy1 and Msy2 [
].
Mitochondrial functions rely on the correct transport of resident proteins
synthesized in the cytosol to mitochondria. Protein import into mitochondriais mediated by membrane protein complexes, protein translocators, in the outer
and inner mitochondrial membranes, in cooperation with their assistantproteins in the cytosol, intermembrane space and matrix. Proteins destined to
the mitochondrial matrix cross the outer membrane with the aid of the outermembrane translocator, the tOM40 complex, and then the inner membrane with the
aid of the inner membrane translocator, the TIM23 complex, and mitochondrial motor and chaperone (MMC) proteins including mitochondrial heat-shock protein 70 (mtHsp70), and translocase in the inner mitochondrial
membrane (Tim)15. Tim15 is also known as zinc finger motif (Zim)17 or mtHsp70escort protein (Hep)1. Tim15 contains a zinc-finger motif (CXXC
and CXXC) of ~100 residues, which has been named DNL after a short C-terminalmotif of D(N/H)L [
,
,
].
Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [,
,
,
,
]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few []. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target. The DNL-type zinc finger is found in Tim15, a zinc finger protein essential for protein import into mitochondria. Mitochondrial functions rely on the correct transport of resident proteins
synthesized in the cytosol to mitochondria. Protein import into mitochondriais mediated by membrane protein complexes, protein translocators, in the outer
and inner mitochondrial membranes, in cooperation with their assistantproteins in the cytosol, intermembrane space and matrix. Proteins destined to
the mitochondrial matrix cross the outer membrane with the aid of the outermembrane translocator, the tOM40 complex, and then the inner membrane with the
aid of the inner membrane translocator, the TIM23 complex, and mitochondrial motor and chaperone (MMC) proteins including mitochondrial heat-shock protein 70 (mtHsp70), and translocase in the inner mitochondrial
membrane (Tim)15. Tim15 is also known as zinc finger motif (Zim)17 or mtHsp70escort protein (Hep)1. Tim15 contains a zinc-finger motif (CXXC
and CXXC) of ~100 residues, which has been named DNL after a short C-terminalmotif of D(N/H)L [
,
,
].The DNL-type zinc finger is an L-shaped molecule. The two
CXXC motifs are located at the end of the L, and are sandwiched by two-stranded antiparallel β-sheets. Two short α-helices constitute another
leg of the L. The outer (convex) face of the L has a large acidic groove,which is lined with five acidic residues, whereas the inner (concave) face of
the L has two positively charged residues, next to the CXXC motifs [].This entry represents the DNL-type zinc finger.
Phosphatidylinositol 3-kinase (PI3-kinase) (
) [
] is an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring. The three products of PI3-kinase - PI-3-P, PI-3,4-P(2) and PI-3,4,5-P(3) function as secondary messengers in cell signalling. Phosphatidylinositol 4-kinase (PI4-kinase) () [
] is an enzyme that acts on phosphatidylinositol (PI) in the first committed step in the production of the secondary messenger inositol-1'4'5'-trisphosphate. This domain is also present in a wide range of protein kinases, involved in diverse cellular functions, such as control of cell growth, regulation of cell cycle progression, a DNA damage checkpoint, recombination, and maintenance of telomere length. Despite significant homology to lipid kinases, no lipid kinase activity has been demonstrated for any of the PIK-related kinases [].The PI3- and PI4-kinases share a well conserved domain at their C-terminal section; this domain seems to be distantly related to the catalytic domain of protein kinases [
,
]. The catalytic domain of PI3/PI4KK has the typical bilobal structure that is seen in other ATP-dependent kinases, divided into an N-lobe and a C-lobe () [
]. The core of this domain is the most conserved region of the PI3Ks. The N-lobe contains a five-stranded antiparallel β-sheet core flanked by a helical hairpin on one side and a helix on the other. The C-lobe contains helices, which form a helical bundle together with the N--obe helix. The helical bundle is flanked by three β-strands and a helix. Three loops are related to kinase activity, the glycine-rich G-loop, the catalytic loop and the activation loop. The G-loop has been reported to bind to the phosphate group of nucleotides [].
The FAT domain is a domain present in the PIK-related kinases. Members of the family of PIK-related kinases may act as intracellular sensors that govern radial and horizontal pathways [
].
Isochorismate synthase (
) catalyses the conversion of chorismate to isochorismate, the first step in the biosynthesis of both the respiratory chain component menaquinone (MK, vitamin K2) and phylloquinone (vitamin K1). In bacteria, isochorismate is a precursor of siderophores enterobactin (via the 2,3-dihydroxybenzoate (DHB) precursor) [
], amonabactins [] and salicylic acid []. Most aerobic bacteria secrete siderophores to facilitate iron acquisition []. Siderophores are iron-chelating agents which are low molecular weight compounds that specifically bind ferric iron and mediate iron uptake into the cell by recognition of specific membrane receptor proteins and transport systems. In plants, isochorismate synthase is required for defence against pathogens. Salicylic acid synthesised via the pathway using isochorismate synthase is responsible for both local and systemic acquired resistance in plants [].In Escherichia coli and Bacillus subtilis, two distinct isochorismate synthase isoenzymes, MenF [
] and EntC []/DhbC [], are known to be involved in MK and siderophore biosynthesis pathways, respectively []. MenF and EntC are differentially regulated and isochorismate synthesised by EntC is mainly channelled into enterobactin synthesis, whereas isochorismate synthesised by MenF is mainly channelled into menaquinone synthesis [].The catalytic/chorismate binding domain characteristic of members of this group is related to other chorismate binding enzymes [
]: component I of anthranilate synthase, para-aminobenzoate synthase, and aminodeoxychorismate synthase (please see ).
There is a significant heterogeneity in the length and sequence of the N-terminal region of members of this group. Partially on the basis of the N-terminal region, the group can be divided into subfamilies, with the enzymes involved in DHB (enterobactin precursor) biosynthesis (EntC/DhbC/VibC) forming a distinct subfamily, and the enzymes involved in MK biosynthesis (MenF) forming two groups (E. coli and B. subtilis types).
This entry represents the catalytic regions of the chorismate binding enzymes anthranilate synthase, isochorismate synthase, aminodeoxychorismate synthase and para-aminobenzoate synthase [
].Anthranilate synthase catalyses the reaction:
chorismate + l-glutamine = anthranilate + pyruvate + l-glutamate.
The enzyme is a tetramer comprising 2 I and 2 II components: this entry is restricted to component I that catalyses the formation of anthranilate using ammonia rather than glutamine, while component II
provides glutamine amidotransferase activity.
This domain in found exclusively in plant proteins, associated with homeobox domain
which may suggest these proteins are homeodomain transcription factors. Proteins containing this domain include BEL1-like homeodomain protein 1 (BLH1) from Arabidopsis thaliana. BLH1 interacts with KNAT2 and KNAT5 [
] and affects plant development [].
Swp1 is an essential subunit of the N-oligosaccharyl transferase (OST) complex which catalyses the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide donor to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains [
]. N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity [].
This entry consists of several Arabidopsis thaliana hypothetical proteins, none of which have any known function. They contain a conserved region with two cysteine residues. This domain exhibits structural similarities with members of the Bet v1-like superfamily and may play a role in lipid binding [
].
This entry represents an enzyme, naphthoate synthase
, MenB or dihydroxynaphthoic acid synthetase, which is involved in the fifth step of the menaquinone biosynthesis pathway. Menaquinone (vitamin K2), is an essential quinone used in electron-transfer pathways serving as the major electron carrier during anaerobic growth. In the bacterium, the biosynthetic pathway in bacteria typically comprises 6-7 steps [
]. Together with o-succinylbenzoate-CoA ligase (menE ),MenB takes 2-succinylbenzoate and converts it into 1,4-di-hydroxy-2-naphthoic acid (DHNA) [
,
,
,
]. The conversion of o-succinylbenzoate-CoA ligase to DHNA is mediated by the enzyme DHNA synthase, which is encoded by menB [].The protein structure of naphthoate synthase has been expressed in Escherichia coli, purified and crystallized, and found to have fold characteristics of the crotonase family of enzymes, which is notable for the presence of several highly flexible regions around the active site. The C-terminal region of the protein may play a critical role both in completion of the binding pocket and in stabilisation of the hexamer, suggesting a link between oligomerisation and catalytic activity [
].
Alanine-tRNA ligase (also known as alanyl-tRNA synthetase) (
) is an alpha4 tetramer that belongs to class IIc.
The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [].
Alanine-tRNA ligase, class IIc, anti-codon-binding domain superfamily
Type:
Homologous_superfamily
Description:
The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [
].
The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [].Alanine-tRNA ligase (also known as alanyl-tRNA synthetase) (
) is an alpha4 tetramer that belongs to class IIc.
The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [
].Alanine-tRNA ligase (also known as alanyl-tRNA synthetase) (
) is an alpha4 tetramer that belongs to class IIc.
A number of plant and fungal proteins that bind N-acetylglucosamine (e.g. solanaceous lectins of tomato and potato, plant endochitinases, the wound-induced proteins: hevein, win1 and win2, and the Kluyveromyces lactis killer toxin alpha subunit) contain this domain [
]. The domain may occur in one or more copies and is thought to be involved in recognition or binding of chitin subunits [,
]. In chitinases, as well as in the potato wound-induced proteins, the 43-residue domain directly follows the signal sequence and is therefore at the N terminus of the mature protein; in the killer toxin alpha subunit it is located in the central section of the protein.
A number of plant and fungal proteins that bind N-acetylglucosamine (e.g. solanaceous lectins of tomato and potato, plant endochitinases, the wound-induced proteins: hevein, win1 and win2, and the Kluyveromyces lactis killer toxin alpha subunit) contain this domain [
]. The domain may occur in one or more copies and is thought to be involved in recognition or binding of chitin subunits [,
]. In chitinases, as well as in the potato wound-induced proteins, the 43-residue domain directly follows the signal sequence and is therefore at the N terminus of the mature protein; in the killer toxin alpha subunit it is located in the central section of the protein.
O-Glycosyl hydrolases (
) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families [
,
]. This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.Glycoside hydrolase family 19
comprises enzymes with only one known activity; chitinase (
).
Chitinases [
] are enzymes that catalyze the hydrolysis of the beta-1,4-N-acetyl-D-glucosamine linkages in chitin polymers. Chitinases belong to glycoside hydrolase families 18 or 19 []. Chitinases of family 19 (also known as classes IA or I and IB or II) are enzymes from plants that function in the defence against fungal and insect pathogens by destroying their chitin-containing cell wall. Class IA/I and IB/II enzymes differ in the presence (IA/I) or absence (IB/II) of a N-terminal chitin-binding domain. The catalytic domain of these enzymes consist of about 220 to 230 amino acid residues. The At2g43600 protein from Arabidopsis thaliana is presumably inactive as a chitinase because it lacks the Glu residue that is essential for catalytic activity.
This group of cysteine peptidases belong to MEROPS peptidase family C15 (pyroglutamyl peptidase I, clan CF). The type example being pyroglutamyl peptidase I of Bacillus amyloliquefaciens. There are similarities in structure between members of clan CF and members of three clans of metallopeptidases (MC, MF and MH) and all four are included in the same superfamily (phosphorylase/hydrolase-like fold) by the SCOP database. Members of clan CF have an alpha/beta/alpha sandwich fold [
].Pyroglutamyl peptidase I (also known as pyrrolidone carboxyl peptidase, Pcp or PYRase) is an exopeptidase that hydrolytically removes the pGlu from pGlu-peptides or pGlu-proteins [
,
]. PYRase has been found in prokaryotes and eukaryotes where at least two different classes have been characterised: the first containing bacterial and animal type I PYRases, and the second containing animal type II and serum PYRases. Type I and bacterial PYRases are soluble enzymes, while type II PYRases are membrane-bound. The primary application of PYRase has been its utilisation for protein or peptide sequencing, and bacterial diagnosis []. The conserved residues Cys-144 and His-168 have been identified by inhibition and mutagenesis studies [,
].
This group of cysteine peptidases belong to MEROPS peptidase family C15 (pyroglutamyl peptidase I, clan CF). The type example being pyroglutamyl peptidase I of Bacillus amyloliquefaciens. There are similarities in structure between members of clan CF and members of three clans of metallopeptidases (MC, MF and MH) and all four are included in the same superfamily (phosphorylase/hydrolase-like fold) by the SCOP database. Members of clan CF have an alpha/beta/alpha sandwich fold [
].Pyroglutamyl peptidase I (also known as pyrrolidone carboxyl peptidase, Pcp or PYRase) is an exopeptidase that hydrolytically removes the pGlu from pGlu-peptides or pGlu-proteins [
,
]. PYRase has been found in prokaryotes and eukaryotes where at least two different classes have been characterised: the first containing bacterial and animal type I PYRases, and the second containing animal type II and serum PYRases. Type I and bacterial PYRases are soluble enzymes, while type II PYRases are membrane-bound. The primary application of PYRase has been its utilisation for protein or peptide sequencing, and bacterial diagnosis []. The conserved residues Cys-144 and His-168 have been identified by inhibition and mutagenesis studies [,
].Pyroglutamyl-peptidase 1-like protein belongs to the petidase C15 family, though its exact function is not known.
The transporter OPT family are transporters of small oligopeptides, demonstrated
experimentally in three different species of yeast. OPT1 is not a member of the ABC or PTR membrane transport families [].
This family consists of several hypothetical glycine rich plant and bacterial proteins of around 300 residues in length. The function of this family is unknown.
One member of this family, from Bidobacterium longicum, UniProtKB:
, has been characterised as an unusual beta-L-arabinofuranosidase enzyme (
). It releases l-arabinose from the l-arabinofuranose (Araf)-beta1,2-Araf disaccharide and also transglycosylates 1-alkanols with retention of the anomeric configuration. Terminal beta-l-arabinofuranosyl residues have been found in arabinogalactan proteins from a number of different plant species. Beta-l-Arabinofuranosyl linkages with 1-4 arabinofuranosides are also found in the sugar chains of extensin and solanaceous lectins, hydroxyproline (Hyp)2-rich glycoproteins that are widely observed in plant cell wall fractions. The critical residue for catalytic activity is Glu-338, in a ET/SCAS sequence context [
].
NAD(P)H-quinone oxidoreductase (NDH-1) shuttles electrons from an unknown electron donor, via FMN and iron-sulphur (Fe-S) centres, to quinones in the respiratory and/or the photosynthetic chain. The immediate electron acceptor for the enzyme in this species is believed to be plastoquinone. It couples the redox reaction to proton translocation, and thus conserves the redox energy in a proton gradient. Cyanobacterial NDH-1 also plays a role in inorganic carbon-concentration. NDH-1 can be composed of about 15 different subunits, although different subcomplexes with different compositions have been identified which probably have different functions.This entry represents subunit N.
Ycf54 is found encoded in the chloroplast genomes of algae, it is also found in plants and in the cyanobacteria. Ycf54 is a component of the MgPME-cyclase complex. Ycf54 plays two roles in the function of the MgPME-cyclase. First, it plays a critical role in t assembly/stability of the Mg-cyclase complex and its constituents and, secondly, is required for normal Pchlide formation. Both functions indicate that this protein is required for optimal MgPME-cyclase activity, although it is not absolutely essential [
].
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 [
,
].Ribosomal protein L17 is one of the proteins from the large ribosomal subunit. Bacterial L17 is a protein of 120 to 130 amino-acid residues while yeast YmL8 is
twice as large (238 residues). The N-terminal half of YmL8 is colinearwith the sequence of L17 from Escherichia coli.
This entry represents the C-terminal domain of MCU, which is a mitochondrial inner membrane calcium uniporter that mediates calcium uptake into mitochondria [
,
,
]. This domain can also be found in MCUb, which negatively regulates the activity of MCU [].
Glutathione peroxidase (GSHPx) (
) is an enzyme that catalyses the reduction of hydroperoxides by glutathione [
]. Its main function is to protect against the damaging effect of endogenously formed hydroperoxides. In higher vertebrates, several forms of GSHPx are known, including a ubiquitous cytosolic form (GSHPx-1), a gastrointestinal cytosolic form (GSHPx-GI), a plasma secreted form (GSHPx-P), and an epididymal secretory form (GSHPx-EP). In mammals there are eight GPx, divided in two clusters, the classical GPx (GPx1, GPx2, GPx3, GPx5 and GPx6) and phospholipid hydroperoxide GPx (GPx4, GPx7 and GPx8). The classical GPx is multimeric (commonly tetrameric) and soluble, while the phospholipid hydroperoxide (PHGPx) is monomeric and often membrane-associated []. In addition to these characterised forms, the sequence of a protein of unknown function [] has been shown to be evolutionary related to those of GSHPx's.In filarial nematode parasites, the major soluble cuticular protein (gp29) is a secreted GSHPx, which may provide a mechanism of resistance to the immune reaction of the mammalian host by neutralising the products of the oxidative burst of leukocytes [
]. The structure of bovine seleno-glutathione peroxidase has been determined []. The protein belongs to the α-β class, with a three layer(aba) sandwich architecture. The catalytic site of GSHPx contains a conserved residue which is either a cysteine or, in many eukaryotic GSHPx, a selenocysteine [].
Citrate synthase
is a member of a small family of enzymes that can directly form a carbon-carbon bond without the presence of metal ion cofactors. It catalyses the first reaction in the Krebs' cycle, namely the conversion of oxaloacetate and acetyl-coenzyme A into citrate and coenzyme A. This reaction is important for energy generation and for carbon assimilation. The reaction proceeds via a non-covalently bound citryl-coenzyme A intermediate in a 2-step process (aldol-Claisen condensation followed by the hydrolysis of citryl-CoA).
Citrate synthase enzymes are found in two distinct structural types: type I enzymes (found in eukaryotes, Gram-positive bacteria and archaea) form homodimers and have shorter sequences than type II enzymes, which are found in Gram-negative bacteria and are hexameric in structure. In both types, the monomer is composed of two domains: a large α-helical domain consisting of two structural repeats, where the second repeat is interrupted by a small α-helical domain. The cleft between these domains forms the active site, where both citrate and acetyl-coenzyme A bind. The enzyme undergoes a conformational change upon binding of the oxaloacetate ligand, whereby the active site cleft closes over in order to form the acetyl-CoA binding site [
]. The energy required for domain closure comes from the interaction of the enzyme with the substrate. Type II enzymes possess an extra N-terminal β-sheet domain, and some type II enzymes are allosterically inhibited by NADH [].This entry represents types I and II citrate synthase enzymes, as well as the related enzymes 2-methylcitrate synthase and ATP citrate synthase. 2-methylcitrate (
) synthase catalyses the conversion of oxaloacetate and propanoyl-CoA into (2R,3S)-2-hydroxybutane-1,2,3-tricarboxylate and coenzyme A. This enzyme is induced during bacterial and fungal growth on propionate [
,
], while type II hexameric citrate synthase is constitutive []. ATP citrate synthase () (also known as ATP citrate lyase) catalyses the MgATP-dependent, CoA-dependent cleavage of citrate into oxaloacetate and acetyl-CoA, a key step in the reductive tricarboxylic acid pathway of CO2 assimilation used by a variety of autotrophic bacteria and archaea to fix carbon dioxide [
]. ATP citrate synthase is composed of two distinct subunits. In eukaryotes, ATP citrate synthase is a homotetramer of a single large polypeptide, and is used to produce cytosolic acetyl-CoA from mitochondrial produced citrate []. This entry includes citrate synthase from Thermosulfidibacter takaii, which catalyses both citrate generation and citrate cleavage as it is part of a reversible tricarboxylic acid (TCA) cycle that can fix carbon dioxide autotrophically and may represent an ancestral mode of the conventional reductive TCA (rTCA) cycle [].There are a number of regions of sequence similarity between prokaryotic and eukaryotic citrate synthases. One of the best conserved contains a histidine which is one of three residues shown to be involved in the catalytic mechanism of the vertebrate mitochondrial enzyme [
]. This entry represents this region.
Citrate synthase
is a member of a small family of enzymes that can directly form a carbon-carbon bond without the presence of metal ion cofactors. It catalyses the first reaction in the Krebs' cycle, namely the conversion of oxaloacetate and acetyl-coenzyme A into citrate and coenzyme A. This reaction is important for energy generation and for carbon assimilation. The reaction proceeds via a non-covalently bound citryl-coenzyme A intermediate in a 2-step process (aldol-Claisen condensation followed by the hydrolysis of citryl-CoA). Citrate synthase enzymes are found in two distinct structural types: type I enzymes (found in eukaryotes, Gram-positive bacteria and archaea) form homodimers and have shorter sequences than type II enzymes, which are found in Gram-negative bacteria and are hexameric in structure. In both types, the monomer is composed of two domains: a large α-helical domain consisting of two structural repeats, where the second repeat is interrupted by a small α-helical domain. The cleft between these domains forms the active site, where both citrate and acetyl-coenzyme A bind. The enzyme undergoes a conformational change upon binding of the oxaloacetate ligand, whereby the active site cleft closes over in order to form the acetyl-CoA binding site [
]. The energy required for domain closure comes from the interaction of the enzyme with the substrate. Type II enzymes possess an extra N-terminal β-sheet domain, and some type II enzymes are allosterically inhibited by NADH [].This entry represents types I and II citrate synthase enzymes, as well as the related enzymes 2-methylcitrate synthase and ATP citrate synthase. 2-methylcitrate (
) synthase catalyses the conversion of oxaloacetate and propanoyl-CoA into (2R,3S)-2-hydroxybutane-1,2,3-tricarboxylate and coenzyme A. This enzyme is induced during bacterial and fungal growth on propionate [
,
], while type II hexameric citrate synthase is constitutive []. ATP citrate synthase () (also known as ATP citrate lyase) catalyses the MgATP-dependent, CoA-dependent cleavage of citrate into oxaloacetate and acetyl-CoA, a key step in the reductive tricarboxylic acid pathway of CO2 assimilation used by a variety of autotrophic bacteria and archaea to fix carbon dioxide [
]. ATP citrate synthase is composed of two distinct subunits. In eukaryotes, ATP citrate synthase is a homotetramer of a single large polypeptide, and is used to produce cytosolic acetyl-CoA from mitochondrial produced citrate []. This entry includes citrate synthase from Thermosulfidibacter takaii, which catalyses both citrate generation and citrate cleavage as it is part of a reversible tricarboxylic acid (TCA) cycle that can fix carbon dioxide autotrophically and may represent an ancestral mode of the conventional reductive TCA (rTCA) cycle [].
Citrate synthase
is a member of a small family of enzymes that can directly form a carbon-carbon bond without the presence of metal ion cofactors. It catalyses the first reaction in the Krebs' cycle, namely the conversion of oxaloacetate and acetyl-coenzyme A into citrate and coenzyme A. This reaction is important for energy generation and for carbon assimilation. The reaction proceeds via a non-covalently bound citryl-coenzyme A intermediate in a 2-step process (aldol-Claisen condensation followed by the hydrolysis of citryl-CoA).
Citrate synthase enzymes are found in two distinct structural types: type I enzymes (found in eukaryotes, Gram-positive bacteria and archaea) form homodimers and have shorter sequences than type II enzymes, which are found in Gram-negative bacteria and are hexameric in structure. In both types, the monomer is composed of two domains: a large α-helical domain consisting of two structural repeats, where the second repeat is interrupted by a small α-helical domain. The cleft between these domains forms the active site, where both citrate and acetyl-coenzyme A bind. The enzyme undergoes a conformational change upon binding of the oxaloacetate ligand, whereby the active site cleft closes over in order to form the acetyl-CoA binding site [
]. The energy required for domain closure comes from the interaction of the enzyme with the substrate. Type II enzymes possess an extra N-terminal β-sheet domain, and some type II enzymes are allosterically inhibited by NADH [].This entry represents the large α-helical domain from type I and II citrate synthase enzymes, as well as a homologous domain found in the related enzyme 2-methylcitrate synthase. 2-Methylcitrate (
) synthase catalyses the conversion of oxaloacetate and propanoyl-CoA into (2R,3S)-2-hydroxybutane-1,2,3-tricarboxylate and coenzyme A. This enzyme is induced during bacterial growth on propionate, while type II hexameric citrate synthase is constitutive [
].
Citrate synthase
is a member of a small family of enzymes that can directly form a carbon-carbon bond without the presence of metal ion cofactors. It catalyses the first reaction in the Krebs' cycle, namely the conversion of oxaloacetate and acetyl-coenzyme A into citrate and coenzyme A. This reaction is important for energy generation and for carbon assimilation. The reaction proceeds via a non-covalently bound citryl-coenzyme A intermediate in a 2-step process (aldol-Claisen condensation followed by the hydrolysis of citryl-CoA).
Citrate synthase enzymes are found in two distinct structural types: type I enzymes (found in eukaryotes, Gram-positive bacteria and archaea) form homodimers and have shorter sequences than type II enzymes, which are found in Gram-negative bacteria and are hexameric in structure. In both types, the monomer is composed of two domains: a large α-helical domain consisting of two structural repeats, where the second repeat is interrupted by a small α-helical domain. The cleft between these domains forms the active site, where both citrate and acetyl-coenzyme A bind. The enzyme undergoes a conformational change upon binding of the oxaloacetate ligand, whereby the active site cleft closes over in order to form the acetyl-CoA binding site [
]. The energy required for domain closure comes from the interaction of the enzyme with the substrate. Type II enzymes possess an extra N-terminal β-sheet domain, and some type II enzymes are allosterically inhibited by NADH [
].This entry represents the small α-helical domain from type I and II citrate synthase enzymes, as well as a homolgous domain found in the related enzyme ATP citrate synthase. ATP citrate synthase (
) (also known as ATP citrate lyase) catalyses the MgATP-dependent, CoA-dependent cleavage of citrate into oxaloacetate and acetyl-CoA, a key step in the reductive tricarboxylic acid pathway of CO2 assimilation used by a variety of autotrophic bacteria and archaea to fix carbon dioxide [
]. ATP citrate synthase is composed of two distinct subunits. In eukaryotes, ATP citrate synthase is a homotetramer of a single large polypeptide, and is used to produce cytosolic acetyl-CoA from mitochondrial-produced citrate [].
The plant GROWTH-REGULATING FACTOR (GRF) proteins are putative transcription factors. They contain one or two WRC (Trp, Arg, Cys) domain(s). The WRC domain has two distinctive structural features, namely many basic amino acids (Arg and Lys) and the conserved spacing of three Cys and one His residues, the C3H motif. The basic amino acids are highly conserved, indicating that they are essential for the function of the WRC domain, probably as nuclear localization signal. The C3H motif is also absolutely conserved and may mediate binding to DNA [
].
The MCM2-7 complex consists of six closely related proteins that are highly conserved throughout the eukaryotic kingdom. In eukaryotes, Mcm7 is a component of the MCM2-7 complex (MCM complex), which consists of six sequence-related AAA + type ATPases/helicases that form a hetero-hexameric ring [
]. MCM2-7 complex is part of the pre-replication complex (pre-RC). In G1 phase, inactive MCM2-7 complex is loaded onto origins of DNA replication [,
,
]. During G1-S phase, MCM2-7 complex is activated to unwind the double stranded DNA and plays an important role in DNA replication forks elongation [].The components of the MCM2-7 complex are:
DNA replication licensing factor MCM2, DNA replication licensing factor MCM3, DNA replication licensing factor MCM4, DNA replication licensing factor MCM5, DNA replication licensing factor MCM6, DNA replication licensing factor MCM7, The human MCM7 gene has been localised to chromosome 7q21.3-q22.1. Increased expression of Mcm7
RNA and protein in MYCN-amplified neuroblastoma tumour and cell lines hasbeen reported [
]. Furthermore, The Mcm7 protein has been shown to formcomplexes with the retinoblastoma protein [
]. These findings suggest Mcm7-directed DNA replication contributes to neoplastic transformation.
Fatty acyl-coenzyme A reductase, NAD-binding domain
Type:
Domain
Description:
This family represents the C-terminal NAD-binding region of the fatty acyl-coenzyme A reductases (FARs) from plants and animals. FARs catalyse the reduction of fatty acyl-CoA to fatty alcohols [
,
]. Proteins containing this domain also include non-ribosomal peptide synthetases and non-reducing polyketide synthases from Aspergillaceae. Non-ribosomal peptide synthetases are part of the gene cluster that mediates the biosynthesis of the lipopeptide antibiotics leucinostatins [
]. Non-reducing polyketide synthases are involved in the secondary metabolite biosynthesis [].Proteins containing this domain also include L-2-aminoadipate reductase from yeast [
] and carboxylic acid reductase (Car) from bacteria [].
The MIT domain forms an asymmetric three-helix bundle. It is found in vacuolar sorting proteins, spastin (probable ATPase involved in the assembly or function of nuclear protein complexes), and a sorting nexin, which may play a role in intracellular trafficking.A 'variant' MIT domain has been described at the N-terminal region of a related AAA-ATPase, mammalian katanin p60 [
].
Poly(ADP-ribose) polymerase catalyses the covalent attachment of ADP-ribose units from NAD+ to itself and to a limited number of other DNA binding proteins, which decreases their affinity for DNA. Poly(ADP-ribose) polymerase is a regulatory component induced by DNA damage. The regulatory domain of the polymerase is almost always associated with the C-terminal catalytic domain (see
).
This domain consists of a duplication of two helix-loop-helix structural repeats [
].
This domain is named after the most conserved central motif of the domain. It is found in a variety of polyA polymerases as well as the Escherichia coli molybdate metabolism regulator
and other proteins of unknown function. The domain is found in isolation in proteins such as
and is between 70 and 90 residues in length. This domain participates in binding DNA near the 5' terminus and mediates domain-domain contacts essential for DNA-dependent activity [,
,
].
Phosphotyrosyl phosphatase activator (PTPA, also known as protein phosphatase 2A activator) proteins stimulate the phosphotyrosyl phosphatase (PTPase) activity of the dimeric form of protein phosphatase 2A (PP2A). PTPase activity in PP2A (in vitro) is relatively low when compared to the better recognised phosphoserine/ threonine protein phosphorylase activity. It also reactivates the serine/threonine phosphatase activity of an inactive form of PP2A. The specific biological role of PTPA is unknown. PTPA has been suggested to play a role in the insertion of metals to the PP2A catalytic subunit (PP2Ac) active site, to act as a chaperone, and more recently, to have peptidyl prolyl cis/trans isomerase activity that specifically targets human PP2Ac [
,
,
,
,
,
]. Together, PTPA and PP2A constitute an ATPase and it has been suggested that PTPA alters the relative specificity of PP2A from phosphoserine/phosphothreonine substrates to phosphotyrosine substrates in an ATP-hydrolysis-dependent manner. Basal expression of PTPA depends on the activity of a ubiquitous transcription factor, Yin Yang 1 (YY1). The tumour suppressor protein p53 can inhibit PTPA expression through an unknown mechanism that negatively controls YY1 [].
Members of the Rho family of small G proteins transduce signals from plasma-membrane
receptors and control cell adhesion, motility and shape by actin cytoskeleton formation.Like all other GTPases, Rho proteins act as molecular switches, with an active
GTP-bound form and an inactive GDP-bound form. The active conformation is promoted byguanine-nucleotide exchange factors, and the inactive state by GTPase-activating proteins
(GAPs) which stimulate the intrinsic GTPase activity of small G proteins.This entry is a Rho/Rac/Cdc42-like GAP domain, that is found in a wide variety of large,
multi-functional proteins [].A number of structure are known for this family
[,
,
].The domain is composed of seven α-helices.
This domain is also known as the breakpoint cluster region-homology (BH) domain.
Proteins containing a RhoGAP (Rho GTPase Activating Protein) domain usually function to catalyse the hydrolysis of GTP that is bound to Rho, Rac and/or Cdc42, inactivating these regulators of the actin cytoskeleton. The 53 known human RhoGAP domain-containing proteins are the largest known group of Rho GTPase regulators and significantly outnumber the 21 Rho GTPases they presumably regulate. This excess of GAP proteins probably indicates complex regulation of the Rho GTPases and is consistent with the existence of almost as many (48) human Dbl domain-containing Rho GEFs that act antagonistically to the RhoGAP proteins by activating the Rho GTPases. Phylogenetic analysis offers evidence for frequent domain duplication and for duplication of the entire genes containing these GAP domains [
].
Catalases (
) are antioxidant enzymes that catalyse the conversion of hydrogen peroxide to water and molecular oxygen, serving to protect cells from its toxic effects [
]. Hydrogen peroxide is produced as a consequence of oxidative cellular metabolism and can be converted to the highly reactive hydroxyl radical via transition metals, this radical being able to damage a wide variety of molecules within a cell, leading to oxidative stress and cell death. Catalases act to neutralise hydrogen peroxide toxicity, and are produced by all aerobic organisms ranging from bacteria to man. Most catalases are mono-functional, haem-containing enzymes, although there are also bifunctional haem-containing peroxidase/catalases () that are closely related to plant peroxidases, and non-haem, manganese-containing catalases (
) that are found in bacteria [
]. Based on a phylogenetic analysis, catalases can be classified into clade 1, 2 and 3. Clade 1 contains small subunit catalases from plants and a subset of bacteria; clade 2 contains large subunit catalases from fungi and a second subset of bacteria; and clade 3 contains small subunit catalases from bacteria, fungi, protists, animals, and plants [,
].This entry represent the core-forming domain of mono-functional, haem-containing catalases. It does not cover the region that carries an immune-responsive amphipathic octa-peptide that is found in the C-terminal of some catalases (
).
This entry represents a fold found in the mono-functional, haem-containing catalases and also in haem peroxidases such as allene oxide synthase [,
,
]. In catalases, this entry covers the core forming domain and, if present, the immune-responsive C-terminal domain.
Catalases (
) are antioxidant enzymes that catalyse the conversion of hydrogen peroxide to water and molecular oxygen, serving to protect cells from its toxic effects [
]. Hydrogen peroxide is produced as a consequence of oxidative cellular metabolism and can be converted to the highly reactive hydroxyl radical via transition metals, this radical being able to damage a wide variety of molecules within a cell, leading to oxidative stress and cell death. Catalases act to neutralise hydrogen peroxide toxicity, and are produced by all aerobic organisms ranging from bacteria to man. Most catalases are mono-functional, haem-containing enzymes, although there are also bifunctional haem-containing peroxidase/catalases () that are closely related to plant peroxidases, and non-haem, manganese-containing catalases (
) that are found in bacteria [
]. Based on a phylogenetic analysis, catalases can be classified into clade 1, 2 and 3. Clade 1 contains small subunit catalases from plants and a subset of bacteria; clade 2 contains large subunit catalases from fungi and a second subset of bacteria; and clade 3 contains small subunit catalases from bacteria, fungi, protists, animals, and plants [,
].This entry represents the mono-functional, haem-containing catalases.
The gene encoding Arabidopsis HAP2 is allelic with GCS1 (Generative cell-specific protein 1). HAP2 is expressed only in the haploid sperm and is required for efficient guidance of the pollen tube to the ovules. In Arabidopsis the protein is a predicted membrane protein with an N-terminal secretion signal, a single transmembrane domain and a C-terminal histidine-rich domain [
]. HAP2-GCS1 is found from plants to lower eukaryotes and is necessary for the fusion of the gametes in fertilisation. It is involved in a novel mechanism for gamete fusion where a first species-specific protein binds male and female gamete membranes together after which a second, broadly conserved protein, either directly or indirectly, causes fusion of the two membranes together. The broadly conserved protein is represented by this HAP2-GCS1 domain, conserved from plants to lower eukaryotes []. In Plasmodium berghei the protein is expressed only in male gametocytes and gametes, having a male-specific function during the interaction with female gametes, and being indispensable for parasite fertilisation. The gene in plants and eukaryotes might well have originated from acquisition of plastids from red algae [].
TRASH domain contains a well-conserved cysteine motif that may be involved in metal coordination. TRASH is encoded by multiple prokaryotic genomes and is present in transcriptional regulators, cation-transporting ATPases and hydrogenases, and is also present as a stand-alone module. The observed domain associations and conserved genome context of TRASH-encoding genes in prokaryotic genomes suggest that TRASH constitutes a novel component in metal trafficking and heavy-metal resistance. The precise role of the multiple copies of TRASH that are present in vertebrate proteins remains to be elucidated [].
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 [
,
].A number of eukaryotic and archaeabacterial ribosomal proteins can be grouped on the basis of sequence
similarities. One of these families [] consists of mammalian ribosomal protein L24; yeastribosomal protein L30A/B (Rp29) (YL21); Kluyveromyces lactis ribosomal protein L30; Arabidopsis thaliana
ribosomal protein L24 homolog; Haloarcula marismortui ribosomal protein HL21/HL22; and Methanocaldococcus jannaschii (Methanococcus jannaschii) MJ1201. These proteins have 60 to 160 amino-acid residues.This entry represents a conserved sequence region found towards the N terminus of
ribosomal protein L24e. It is also found in ribosomal protein L24-like, an essential protein with similarity to Rpl24Ap and Rpl24Bp, which is associated with pre-60S ribosomal subunits and required for ribosomal large subunit biogenesis [,
].
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 [,
].A number of eukaryotic and archaeabacterial ribosomal proteins can be grouped on the basis of sequence
similarities. One of these families [] consists of mammalian ribosomal protein L24; yeastribosomal protein L30A/B (Rp29) (YL21); Kluyveromyces lactis ribosomal protein L30; Arabidopsis thaliana
ribosomal protein L24 homolog; Haloarcula marismortui ribosomal protein HL21/HL22; and Methanocaldococcus jannaschii (Methanococcus jannaschii) MJ1201. These proteins have 60 to 160 amino-acid residues.Ribosomal protein L24e/L24 is a ribosomal protein found in eukaryotes (L24) and in archaea (L24e, distinct from archaeal L24). L24e/L24 is located on the surface of the large subunit, adjacent to proteins L14 and L3, and near the translation factor binding site. L24e/L24 appears to play a role in the kinetics of peptide synthesis, and may be involved in interactions between the large and small subunits, either directly or through other factors. In mouse, a deletion mutation in L24 has been identified as the cause for the belly spot and tail (Bst) mutation that results in disrupted pigmentation, somitogenesis and retinal cell fate determination [
]. L24 may be an important protein in eukaryotic reproduction: in shrimp, L24 expression is elevated in the ovary, suggesting a role in oogenesis [], and in Arabidopsis, L24 has been proposed to have a specific function in gynoecium development [].The crystal structure of the L24e protein from Halobacterium marismortui (Haloarcula marismortui) has been determined [
,
]. The protein is composed of a single structural domain which forms an alpha/beta zinc-binding fold.
tRNA dimethylallyltransferase alternative names include delta(2)-isopentenylpyrophosphate transferase, IPP transferral and 2-methylthio-N6-isopentyladenosine tRNA modification enzyme. This enzyme catalyses the first step in the modification of an adenosine near the anticodon to 2-methylthio-N6-isopentyladenosine [
].Plants have two classes of isopentenyltransferases (IPTs): ATP/ADP isopentenyltransferases (IPT1, 3, 4-8) and tRNA IPTs (IPT2 and 9) [
]. Both types are included in this family.
Transposase proteins are necessary for efficient DNA transposition. This family includes various probable plant transposases from the Ptta and En/Spm families [
,
].
Cytochrome c oxidase (
) is an oligomeric enzymatic complex which is a component of the respiratory chain complex and is involved in the transfer of electrons from cytochrome c to oxygen [
]. In eukaryotes this enzyme complex is located in the mitochondrial inner membrane; in aerobic prokaryotes it is found in the plasma membrane.In eukaryotes, in addition to the three large subunits, I, II and III, that form the catalytic centre of the enzyme complex, there are a variable number of small polypeptidic subunits. This family is composed of the heart and liver isoforms of cytochrome c oxidase subunit VIIa. Subunit VIIa has two tissue-specific isoforms that are expressed in a developmental manner. VIIa-H is expressed in heart and skeletal muscle but not smooth muscle. VIIa-L is expressed in liver and non-muscle tissues [
].
This entry represents RAB6-interacting golgin, including SCYL1BP1 (also known as GORAB) from humans. SCYL1BP1 localises to the Golgi apparatus and interacts with Rab6 [
,
]. Therefore, SCYL1BP1 is identified as a golgin, a protein that tether vesicles to the Golgi apparatus. This entry also includes plant proteins, such as TaSRG (
) from wheat. TaSRG plays a role in stress response in plants [
].
Catabolism and synthesis of leucine, isoleucine and valine are finely balanced, allowing the body to make the most of dietary input but removing excesses to prevent toxic build-up of their corresponding keto-acids. Regulating the activity of the branched-chain alpha-ketoacid dehydrogenase (BCDH) complex is the primary means by which these processes are coordinated. BCDH kinase regulates BCDH by phosphorylation, thereby inactivating it when synthesis is required. Pyruvate dehydrogenase kinase inhibits the pyruvate dehydrogenase complex by phosphorylation of the E1 alpha subunit, thus contributing to the regulation of glucose metabolism. It is also involved in telomere maintenance.This entry is associated with
which is found towards the C terminus.
The TCP-1 protein [
,
] (Tailless Complex Polypeptide 1) was first identified in mice where it is especially abundant in testis but present in all cell types. It has since been found and characterised in many other animal species, as well as in yeast, plants and protists. TCP-1 is a highly conserved protein of about 60kDa (556 to 560 residues) which participates in a hetero-oligomeric 900kDa double-torus shaped particle [] with 6 to 8 other different subunits. These subunits, the chaperonin containing TCP-1 (CCT) subunit beta, gamma, delta, epsilon, zeta and eta are evolutionary related to TCP-1 itself [,
]. The CCT is known to act as a molecular chaperone for tubulin, actin and probably some other proteins.
The CCT subunits are highly related to archaebacterial counterparts:TF55 and TF56 [
], a molecular chaperone from Sulfolobus shibatae. TF55 has ATPase activity, is known to bind unfolded polypeptides and forms a oligomeric complex of two stacked nine-membered rings.Thermosome [
], from Thermoplasma acidophilum. The thermosome is composed of two subunits (alpha and beta) and also seems to be a chaperone with ATPase activity. It forms an oligomeric complex of eight-membered rings.The TCP-1 family of proteins are weakly, but significantly [
], related to the cpn60/groEL chaperonin family (see ).
Members of this eukaryotic family are part of the group II chaperonin complex called CCT (chaperonin containing TCP-1 or Tailless Complex Polypeptide 1) or TRiC [
,
]. Chaperonins are involved in productive folding of proteins []. They share a common general morphology, a double toroid of 2 stacked rings. The archaeal equivalent group II chaperonin is often called the thermosome []. Both the thermosome and the TCP-1 family of proteins are weakly, but significantly [], related to the cpn60/groEL chaperonin family (see ).
The TCP-1 protein was first identified in mice where it is especially abundant in testis but present in all cell types. It has since been found and characterised in many other animal species, as well as in yeast, plants and protists. The TCP1 complex has a double-ring structure with central cavities where protein folding takes place [
]. TCP-1 is a highly conserved protein of about 60kDa (556 to 560 residues) which participates in a hetero-oligomeric 900kDa double-torus shaped particle [] with 6 to 8 other different, but homologous, subunits []. These subunits, the chaperonin containing TCP-1 (CCT) subunit beta, gamma, delta, epsilon, zeta and eta are evolutionary related to TCP-1 itself [,
]. Non-native proteins are sequestered inside the central cavity and folding is promoted by using energy derived from ATP hydrolysis [,
,
]. The CCT is known to act as a molecular chaperone for tubulin, actin and probably some other proteins [,
].This family consists exclusively of the CCT beta chain (part of a paralogous family) from animals, plants, fungi, and other eukaryotes.
