Members of the myosin superfamily of actin-based motors act in a variety of
cellular functions such as muscle contraction, cell and organelle movement,membrane trafficking, and signal transduction. Although myosin motor domains show a high degree of sequence conservation, the individual
myosin classes are clearly defined by differences in the head structure. TheN-terminal region of myosins from different classes varies greatly in length
and amino acid composition among the individual members. Many myosins have anSH3-like domain at the N terminus of the motor domain. This includes myosins
in classes II, V, VI, XI, XXII and XXIV. The myosin N-terminal SH3-like domainmay mediate some aspect of the conformational communication that occurs within
the myosin head during actin and nucleotide binding. Part of this effect maybe mediated through interactions with the neck-associated essential light
chains that are in close proximity to this portion of the head domain and alsotransiently interact with actin [
,
,
].The myosin N-terminal SH3-like domain comprises ~50 amino acids and forms a
protruding, six-stranded, antiparallel, β-barrel domainwith similarities to the SH3 domain [
,
].
Secretion across the inner membrane in some Gram-negative bacteria occurs via the preprotein translocase pathway. Proteins are produced in the cytoplasm as precursors, and require a chaperone subunit to direct them to the translocase component [
]. From there, the mature proteins are either targeted to the outer membrane, or remain as periplasmic proteins. The translocase protein subunits are encoded on the bacterial chromosome.
The translocase itself comprises 7 proteins, including a chaperone protein (SecB), an ATPase (SecA), an integral membrane complex (SecY, SecE and SecG), and two additional membrane proteins that promote the release of the mature peptide into the periplasm (SecD and SecF) [
]. The chaperone protein SecB [] is a highly acidic homotetrameric protein that exists as a "dimer of dimers"in the bacterial cytoplasm. SecB maintains preproteins in an unfolded state after translation, and targets these to the peripheral membrane protein ATPase SecA for secretion [
]. The structure of the Escherichia coli SecYEG assembly revealed a sandwich of two membranes interacting through the extensive cytoplasmic domains []. Each membrane is composed of dimers of SecYEG. The monomeric complex contains 15 transmembrane helices. The eubacterial secY protein [
] interacts with the signal sequences of secretory proteins as well as with two other components of the protein translocation system: secA and secE. SecY is an integral plasma membrane protein of 419 to 492 amino acid residues that apparently contains 10 transmembrane (TM), 6 cytoplasmic and 5 periplasmic regions. Cytoplasmic regions 2 and 3, and TM domains 1, 2, 4, 5, 7 and 10 are well conserved: the conserved cytoplasmic regions are believed to interact with cytoplasmic secretion factors, while the TM domains may participate in protein export [
]. Homologs of secY are found in archaebacteria []. SecY is also encoded in the chloroplast genome of some algae [] where it could be involved in a prokaryotic-like protein export system across the two membranes of the chloroplast endoplasmic reticulum (CER) which is present in chromophyte and cryptophyte algae.This superfamily represents the structural domain of SecY [
].
This family consists of the protein translocase subunit SecY and protein transport protein Sec61 subunit alpha (Sec61a).Sec61a is part of the Sec61 complex, which plays a crucial role in the insertion of secretory and membrane polypeptides into the ER. It is required for assembly of membrane and secretory proteins. Secretion across the inner membrane in some Gram-negative bacteria occurs via the preprotein translocase pathway. Proteins are produced in the cytoplasm as precursors, and require a chaperone subunit to direct them to the translocase component [
]. From there, the mature proteins are either targeted to the outer membrane, or remain as periplasmic proteins. The translocase protein subunits are encoded on the bacterial chromosome.The translocase itself comprises 7 proteins, including a chaperone protein (SecB), an ATPase (SecA), an integral membrane complex (SecY, SecE and SecG), and two additional membrane proteins that promote the release of the mature peptide into the periplasm (SecD and SecF) [
]. The chaperone protein SecB [] is a highly acidic homotetrameric protein that exists as a "dimer of dimers"in the bacterial cytoplasm. SecB maintains preproteins in an unfolded state after translation, and targets these to the peripheral membrane protein ATPase SecA for secretion [
]. The structure of the Escherichia coli SecYEG assembly revealed a sandwich of two membranes interacting through the extensive cytoplasmic domains []. Each membrane is composed of dimers of SecYEG. The monomeric complex contains 15 transmembrane helices. The eubacterial secY protein [
] interacts with the signal sequences of secretory proteins as well as with two other components of the protein translocation system: secA and secE. SecY is an integral plasma membrane protein of 419 to 492 amino acid residues that apparently contains 10 transmembrane (TM), 6 cytoplasmic and 5 periplasmic regions. Cytoplasmic regions 2 and 3, and TM domains 1, 2, 4, 5, 7 and 10 are well conserved: the conserved cytoplasmic regions are believed to interact with cytoplasmic secretion factors, while the TM domains may participate in protein export [
]. Homologs of secY are found in archaebacteria []. SecY is also encoded in the chloroplast genome of some algae [] where it could be involved in a prokaryotic-like protein export system across the two membranes of the chloroplast endoplasmic reticulum (CER) which is present in chromophyte and cryptophyte algae.
The Sec61/SecY translocon mediates translocation of proteins across the membrane and integration of membrane proteins into the lipid bilayer. The structure of the translocon revealed a plug domain blocking the pore on the lumenal side. The plug is unlikely to be important for sealing the translocation pore in yeast but it plays a role in stabilising Sec61p during translocon formation. The domain runs from residues 52-74 [
].
Aromatic ring hydroxylating dioxygenases are multicomponent 1,2-dioxygenase complexes that convert closed-ring structures to non-aromatic cis-diols []. The complex has both hydroxylase and electron transfer components. The hydroxylase component is itself composed of two subunits: an alpha-subunit of about 50kDa, and a beta-subunit of about 20kDa. The electron transfer component is either composed of two subunits: a ferredoxin and a ferredoxin reductase or by a single bifunctional ferredoxin/reductase subunit. Sequence analysis of hydroxylase subunits of ring hydroxylating systems (including toluene, benzene and napthalene 1,2-dioxygenases) suggests they are derived from a common ancestor []. The alpha-subunit binds both a Rieske-like 2Fe-2S cluster and an iron atom: conserved Cys and His residues in the N-terminal region may provide 2Fe-2S ligands, while conserved His and Tyr residues may coordinate the iron. The beta subunit may be responsible for the substrate specificity of the dioxygenase system [].
Aromatic ring hydroxylating dioxygenases are multicomponent 1,2-dioxygenase complexes that convert closed-ring structures to non-aromatic cis-diols [
]. The complex has both hydroxylase and electron transfer components. The hydroxylase component is itself composed of two subunits: an alpha-subunit of about 50kDa, and a beta-subunit of about 20kDa. The electron transfer component is either composed of two subunits: a ferredoxin and a ferredoxin reductase or by a single bifunctional ferredoxin/reductase subunit. Sequence analysis of hydroxylase subunits of ring hydroxylating systems (including toluene, benzene and napthalene 1,2-dioxygenases) suggests they are derived from a common ancestor []. The alpha-subunit binds both a Rieske-like 2Fe-2S cluster and an iron atom: conserved Cys and His residues in the N-terminal region may provide 2Fe-2S ligands, while conserved His and Tyr residues may coordinate the iron. The beta subunit may be responsible for the substrate specificity of the dioxygenase system [].This entry represents the conserved C-terminal domain found in the alpha subunit of aromatic-ring-hydroxylating dioxygenases. It is the catalytic domain of aromatic-ring- hydroxylating dioxygenase systems. The active site contains a non-heme ferrous ion coordinated by three ligands.
This domain is found in squalene epoxidase (SE) and related proteins which are found in taxonomically diverse groups of eukaryotes and also in bacteria. SE was first cloned from Saccharomyces cerevisiae (Baker's yeast) where it was named ERG1. It contains a putative FAD binding site and is a key enzyme in the sterol biosynthetic pathway [
]. Putative transmembrane regions are found to the protein's C terminus.
Transaldolase (
) catalyses the reversible transfer of a three-carbon ketol unit from sedoheptulose 7-phosphate to glyceraldehyde 3-phosphate to form erythrose 4-phosphate and fructose 6-phosphate. This enzyme, together with transketolase, provides a link between the glycolytic and pentose-phosphate pathways. Transaldolase is an enzyme of about 34kDa whose sequence has been well conserved throughout evolution. A lysine has been implicated [
] in the catalytic mechanism of the enzyme; it acts as a nucleophilic group that attacks the carbonyl group of fructose-6-phosphate.
This entry groups metazoan phosphatidylethanolamine-binding proteins, carboxypeptidase Y inhibitor from Saccharomyces cerevisiae (Baker's yeast) (), and homologues from plants which function in flower development. The members of this family belong to MEROPS proteinase inhibitor family I51, clan I-.
In metazoa the phosphatidylethanolamine-binding proteins are an around 200 residue and found in a variety of tissues [
]. They bind hydrophobic ligands, such as phosphatidylethanolamine, but also seems [] to bind nucleotides such as GTP and FMN, it has been suggested that they could act in membrane remodelling during growth and maturation.In plants, the phosphatidylethanolamine-binding protein homologues, include:CENTRORADIALIS (CEN) [
]
SELF PRUNING (SP) [
] TERMINAL FLOWER 1 (TFL1) FLOWERING LOCUS T (FT) MOTHER OF FT AND TFL1 (MTF) [
]
In Arabidopsis thaliana (Mouse-ear cress), FT together with LEAFY (LFY),
, promote flowering and are positively regulated by the transcription factor CONSTANS (CO). Loss of FT causes delay in flowering, whereas over expression of FT results in precocious flowering independent of CO or photoperiod. FT acts in part downstream of CO and mediates signals for flowering in an antagonistic manner with its homologous gene, TERMINAL FLOWER1 (TFL1) [
].
Heparan sulfate acetyl-CoA:alpha-glucosaminide N-acetyltransferase (HGSNAT) catalyzes the transmembrane acetylation of heparan sulfate in lysosomes required for its further catabolism. Mutations of the HGSNAT gene cause the neurodegenerative disease mucopolysaccharidosis IIIC (MPS IIIC) [
].This entry represents the catalytic domain of HGSNAT which contains the conserved histidine in the active site (His269), thought to hold the acetyl group during the transfer across the membrane and required for its enzymatic activity [
].
A conserved domain of 46 amino acids, called WHEP-TRS has been shown [
] to exist in a number of higher eukaryote aminoacyl-transfer RNA synthetases. This domain is present one to six times in the several enzymes. There are three copies in mammalian multifunctional aminoacyl-tRNA synthetase in a region that separates the N-terminal glutamyl-tRNA synthetase domain from the C-terminal prolyl-tRNA synthetase domain, and six copies in the intercatalytic region of the Drosophila enzyme. The domain is found at the N-terminal extremity of the mammalian tryptophanyl-tRNA synthetase and histidyl-tRNA synthetase, and the mammalian, insect, nematode and plant glycyl-tRNA synthetases []. The structure of a human WHEP-TRS domain has been solved and consists of two helices arranged in a helix-turn-helix []. The WHEP-TRS domain may play a role in the association of tRNA-synthetases into multienzyme complexes [].
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 [].In eubacteria, glycine-tRNA ligase (
) is an α2/β2 tetramer composed of 2 different subunits [
,
,
]. In some eubacteria, in archaea and eukaryota, glycine-tRNA ligase is an α2 dimer, this family. It belongs to class IIc and is one of the most complex ligases. What is most interesting is the lack of similarity between the two types: divergence at the sequencelevel is so great that it is impossible to infer descent from common genes. The alpha (see
) and beta subunits (see
) also lack significant sequence similarity. However, they are translated from a single mRNA [
], and a single chain glycine-tRNA ligase from Chlamydia trachomatis has been found to have significant similarity with both domains, suggesting divergence from a single polypeptide chain [
].The sequence and crystal structure of the homodimeric glycine-tRNA ligase from Thermus thermophilus, shows that each monomer consists of an active site strongly resembling that of the aspartyl and seryl enzymes, a C-terminal anticodon recognition domain of 100 residues and a third domain unusually inserted between motifs 1 and 2 almost certainly interacting with the acceptor arm of tRNA(Gly). The C-terminal domain has a novel five-stranded parallel-antiparallel β-sheet structure with three surrounding helices. The active site residues most probably responsible for substrate recognition, in particular in the Gly binding pocket, can be identified by inference from aspartyl-tRNA ligase due to the conserved nature of the class II active site [
,
].
This family includes both Glycyl-tRNA synthetases and mitochondrial DNA polymerase subunit gamma-2 (POLG2). Glycyl-tRNA synthetase catalyses the attachment of glycine to tRNA(Gly). The DNA polymerase gamma-2 subunit acts as a processivity factor to stimulate the catalytic subunit of DNA polymerase gamma. Pol gamma-2 shares conserved sequence blocks with prokaryotic class II aminoacyl-tRNA synthetases, and these are necessary for activity and inter-action with the catalytic subunit [
].
This entry represents the N-terminal domain of glutamyl-tRNA reductase (
), which reduces glutamyl-tRNA to glutamate-1-semialdehyde during the first stage of tetrapyrrole biosynthesis by the C5 pathway [
,
]. The enzyme requires NADPH as a cofactor. This N-terminal domain is the catalytic domain [].
This entry represents a domain found in shikimate and quinate dehydrogenases, as well as glutamyl-tRNA reductases.Shikimate 5-dehydrogenase (
) catalyses the conversion of shikimate to 5-dehydroshikimate [
,
]. This reaction is part of the shikimate pathway which is involved in the biosynthesis of aromatic amino acids []. Quinate 5-dehydrogenase catalyses the conversion of quinate to 5-dehydroquinate. This reaction is part of the quinate pathway where quinic acid is exploited as a source of carbon in prokaryotes and microbial eukaryotes. Both the shikimate and quinate pathways share two common pathway metabolites, 3-dehydroquinate and dehydroshikimate.Glutamyl-tRNA reductase (
) catalyzes the first step of tetrapyrrole biosynthesis in plants, archaea and most bacteria. The dimeric enzyme has an unusual V-shaped architecture where each monomer consists of three domains linked by a long 'spinal' α-helix. The central catalytic domain specifically recognises the glutamate moiety of the substrate [
].
Delta-aminolevulinic acid (ALA) is the obligatory precursor for the synthesis of all tetrapyrroles including porphyrin derivatives such as chlorophyll and heme. ALA can be synthesized via two different pathways: the Shemin (or C4) pathway which involves the single step condensation of succinyl-CoA and glycine and which is catalyzed by ALA synthase and via the C5 pathway from the five-carbon skeleton of glutamate. The C5 pathway operates in the chloroplast of plants and algae, in cyanobacteria, in some eubacteria and in archaebacteria [
].The initial step in the C5 pathway is carried out by glutamyl-tRNA reductase (GluTR) which catalyzes the NADP-dependent conversion of glutamate- tRNA(Glu) to glutamate-1-semialdehyde (GSA) with the concomitant release of tRNA(Glu) which can then be recharged with glutamate by glutamyl-tRNA synthetase [
].This entry represents the conserved site of glutamyl-tRNA reductase. This region seems important for the activity of the enzyme.
Tetrapyrroles are large macrocyclic compounds derived from a common biosynthetic pathway [
]. The end-product, uroporphyrinogen III, is used to synthesise a number of important molecules, including vitamin B12, haem, sirohaem, chlorophyll, coenzyme F430 and phytochromobilin [].The first stage in tetrapyrrole synthesis is the synthesis of 5-aminoaevulinic acid ALA via two possible routes: (1) condensation of succinyl CoA and glycine (C4 pathway) using ALA synthase (
), or (2) decarboxylation of glutamate (C5 pathway) via three different enzymes, glutamyl-tRNA synthetase (
) to charge a tRNA with glutamate, glutamyl-tRNA reductase (
) to reduce glutamyl-tRNA to glutamate-1-semialdehyde (GSA), and GSA aminotransferase (
) to catalyse a transamination reaction to produce ALA.
The second stage is to convert ALA to uroporphyrinogen III, the first macrocyclic tetrapyrrolic structure in the pathway. This is achieved by the action of three enzymes in one common pathway: porphobilinogen (PBG) synthase (or ALA dehydratase,
) to condense two ALA molecules to generate porphobilinogen; hydroxymethylbilane synthase (or PBG deaminase,
) to polymerise four PBG molecules into preuroporphyrinogen (tetrapyrrole structure); and uroporphyrinogen III synthase (
) to link two pyrrole units together (rings A and D) to yield uroporphyrinogen III.
Uroporphyrinogen III is the first branch point of the pathway. To synthesise cobalamin (vitamin B12), sirohaem, and coenzyme F430, uroporphyrinogen III needs to be converted into precorrin-2 by the action of uroporphyrinogen III methyltransferase (
). To synthesise haem and chlorophyll, uroporphyrinogen III needs to be decarboxylated into coproporphyrinogen III by the action of uroporphyrinogen III decarboxylase (
) [
].This entry represents the helical dimerisation domain of glutamyl-tRNA reductase (
) [
]. This enzyme reduces glutamyl-tRNA to glutamate-1-semialdehyde during the first stage of tetrapyrrole biosynthesis by the C5 pathway [,
]. The enzyme requires NADPH as a cofactor.
Delta-aminolevulinic acid (ALA) is the obligatory precursor for the synthesis of all tetrapyrroles including porphyrin derivatives such as chlorophyll and heme. ALA can be synthesized via two different pathways: the Shemin (or C4) pathway which involves the single step condensation of succinyl-CoA and glycine and which is catalyzed by ALA synthase and via the C5 pathway from the five-carbon skeleton of glutamate. The C5 pathway operates in the chloroplast of plants and algae, in cyanobacteria, in some eubacteria and in archaebacteria [
].The initial step in the C5 pathway is carried out by glutamyl-tRNA reductase (GluTR) which catalyzes the NADP-dependent conversion of glutamate- tRNA(Glu) to glutamate-1-semialdehyde (GSA) with the concomitant release of tRNA(Glu) which can then be recharged with glutamate by glutamyl-tRNA synthetase [
].This entry represents glutamyl-tRNA reductase (
), which required NADPH as a coenzyme [
,
]. This entry also includes the multifunctional siroheme biosynthesis protein HemA from Clostridium josuiwhich besides acting as a glutamyl-tRNA reductase also converts precorrin-2 to sirohydrochlorin and sirohydrochlorin to siroheme [
].
This family consists of several eukaryotic Organic-Anion-Transporting Polypeptides (OATPs). Several have been identified mostly in human and rat. Different OATPs vary in tissue distribution and substrate specificity. Since the numbering of different OATPs in particular species was based originally on the order of discovery, similarly numbered OATPs in humans and rats did not necessarily correspond in function, tissue distribution and substrate specificity (in spite of the name, some OATPs also transport organic cations and neutral molecules) so a scheme of using digits for rat OATPs and letters for human ones was introduced [
]. Prostaglandin transporter (PGT) proteins are also considered to be OATP family members. In addition, the methotrexate transporter OATK is closely related to OATPs. This family also includes several predicted proteins from Caenorhabditis elegans and Drosophila melanogaster. This similarity was not previously noted. All characterized OATPs are predicted to have 12 transmembrane domains and are sodium-independent transport systems [].
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 zeta chain (part of a paralogous family) from animals, plants, fungi, and other eukaryotes.
Molecular chaperones are a diverse family of proteins that function to protect proteins in the intracellular milieu from irreversible aggregation during synthesis and in times of cellular stress. The bacterial molecular chaperone DnaK is an enzyme that couples cycles of ATP binding, hydrolysis, and ADP release by an N-terminal ATP-hydrolysing domain to cycles of sequestration and release of unfolded proteins by a C-terminal substrate binding domain. In prokaryotes, the grpE protein is a co-chaperone for DnaK, and acts as a nucleotide exchange factor, stimulating the rate of ADP release 5000-fold [
]. DnaK is itself a weak ATPase; ATP hydrolysis by DnaK is stimulated by its interaction with another co-chaperone, DnaJ. Thus the co-chaperones DnaJ and GrpE are capable of tightly regulating the nucleotide-bound and substrate-bound state of DnaK in ways that are necessary for the normal housekeeping functions and stress-related functions of the DnaK molecular chaperone cycle.Members of this family are the chaperone DnaK, of the DnaK-DnaJ-GrpE chaperone system. All members of the seed alignment were taken from completely sequenced bacterial or archaeal genomes and (except for the Mycoplasma sequence) found clustered with other genes of this systems. This entry excludes DnaK homologues that are not DnaK itself, such as the heat shock cognate protein HscA (
). However, it is not designed to distinguish among DnaK paralogs in eukaryotes. Note that a number of DnaK genes have shadow ORFs in the same reverse (relative to dnaK) reading frame, a few of which have been assigned glutamate dehydrogenase activity. The significance of this observation is unclear; the lengths of such shadow ORFs are highly variable as if the presumptive protein product is not conserved.
This domain is present in aminoacyl-tRNA synthetases (aaRSs), enzymes that couple tRNAs to their cognate amino acids [
]. aaRSs from cyanobacteria containing the CAAD (for cyanobacterial aminoacyl-tRNA synthetases appended domain) protein domains are localised in the thylakoid membrane. The domain bears two putative transmembrane helices and is present in glutamyl-, isoleucyl-, leucyl-, and valyl-tRNA synthetases, the latter of which has probably recruited the domain more than once during evolution.
This small acidic protein is found in 30S ribosomal subunit of cyanobacteria and plant plastids. In plants it has been named plastid-specific ribosomal protein 3 (PSRP-3), and in cyanobacteria it is named Ycf65. Plastid-specific ribosomal proteins may mediate the effects of nuclear factors on plastid translation. The acidic PSRPs are thought to contribute to protein-protein interactions in the 30S subunit, and are not thought to bind RNA [
].
Thiazole synthase (ThiG) is the tetrameric enzyme involved in the formation of the thiazole moiety of thiamin pyrophosphate, an essential ubiquitous cofactor that plays an important role in carbohydrate and amino acid metabolism. ThiG catalyzes the formation of thiazole from 1-deoxy-D-xylulose 5-phosphate (DXP) and dehydroglycine, with the help of the sulfur carrier protein ThiS that carries the sulfur needed for thiazole assembly on its carboxy terminus (ThiS-COSH) [
,
].
This entry includes a group of lipid droplet-associated hydrolases (LDAHs) from eukaryotes. Human LDAH plays a role in cholesterol homeostasis [
]. This entry also includes budding yeast Lipid droplet-associated triacylglycerol lipase YPR147C, which shows both triacylglycerol (TAG) lipase and ester hydrolase activities [].
Proteins containing the ancient conserved domain protein/cyclin M (CNNM) are integral membrane proteins that are conserved from bacteria to humans. CNNM family members influence metal ion homeostasis through mechanisms that may not involve direct membrane transport of the ions. Structurally, CNNMs are complex proteins that contain an extracellular N-terminal domain preceding a transmembrane domain, a "Bateman module", which consists of two cystathionine-beta-synthase (CBS) domains, and a C-terminal cNMP (cyclic nucleotide monophosphate) binding domain [
,
,
,
,
].The CNNM transmembrane domain contains four hydrophobic regions and forms a dimer through hydrophobic contacts between TM2 and TM3, in which each chain is composed of three transmembrane helices (TM1-3), a pair of short helices exposed on the intracellular side, and a juxtamembrane (JM) helix that forms a belt-like structure [
,
]. The homodimer adopts an inward-facing conformation with a negatively charged cavity containing a conserved pi-helical turn in TM3 that coordinates a Mg2 ion [].
Aminotransferases share certain mechanistic features with other pyridoxal-phosphate dependent enzymes, such as the covalent binding of the pyridoxal-phosphate group to a lysine residue. On the basis of sequence similarity, these various enzymes can be grouped [
] into subfamilies.One of these, called class-IV, currently consists of proteins of about 270 to 415 amino-acid residues that share a few regions of sequence similarity. Surprisingly, the best conserved region does not include the lysine residue to which the pyridoxal-phosphate group is known to be attached, in ilvE, but is located some 40 residues at the C terminus side of the pyridoxal-phosphate-lysine. The D-amino acid transferases (D-AAT), which are among the members of this entry, are required by bacteria to catalyse the synthesis of D-glutamic acid and D-alanine, which are essential constituents of bacterial cell wall and are the building block for other D-amino acids. Despite the difference in the structure of the substrates, D-AATs and L-ATTs have strong similarity [
,
]. The proteins in this entry are about 270 to 415 amino-acid residues and all share a few regions of sequence similarity. Surprisingly, the best conserved region does not include the lysine residue to which the pyridoxal-phosphate group is known to be attached, in IlvE. The region used for this signature pattern is located some 40 residues at the C terminus side of the PlP-lysine.
This family of proteins is found in bacteria and plants. It includes abscisic acid (ABA)-deficient 4 protein (ABA4) from Arabidopsis thaliana, which has a role in neoxanthin synthesis [
] and may be important for the de novo ABA synthesis specifically during dehydration [].
This entry represents the N-terminal domain of Serine-tRNA synthetase, which consists of two helices in a long alpha-hairpin and corresponds to the tRNA binding domain. Serine-tRNA synthetase (
) exists as monomer and belongs to class IIa aminoacyl-tRNA synthetase [
].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 a domain found in C terminus of Atg11. Proteins containing this domain include Taf1 and Atg11. In Schizosaccharomyces pombe (fission yeast) Taf1 (taz1 interacting factor) is part of the telomere cap complex. In Saccharomyces cerevisiae (baker's yeast) Atg11 is known to be involved in vacuolar targeting and peroxisome degradation [
,
].
This entry represents the β-propeller domain found at the N-terminal of prolyl oligopeptidase from the MEROPS peptidase family S9A. The prolyl oligopeptidase family consist of a number of evolutionary related peptidases whose catalytic activity seems to be provided by a charge relay system similar to that of the trypsin family of serine proteases, but which evolved by independent convergent evolution. The N-terminal domain of prolyl oligopeptidases form an unusual 7-bladed β-propeller consisting of seven 4-stranded β-sheet motifs.Prolyl oligopeptidase is a large cytosolic enzyme involved in the maturation and degradation of peptide hormones and neuropeptides, which relate to the induction of amnesia. The enzyme contains a peptidase domain, where its catalytic triad (Ser554, His680, Asp641) is covered by the central tunnel of the N-terminal β-propeller domain. In this way, large structured peptides are excluded from the active site, thereby protecting larger peptides and proteins from proteolysis in the cytosol [
].
Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes [
]. They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence []. Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases [
].Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base [
]. The geometric orientations of the catalytic residues are similar between families, despite different protein folds []. The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) [,
].This group of serine peptidases belong to MEROPS peptidase family S9 (clan SC), subfamily S9A (prolyl oligopeptidase). The active site of members of this clan consists of a linear
arrangement of serine, histidine and threonine catalytic residues []. Prolyl oligopeptidases are either located in the cytosol or they are membrane bound, where they cleave peptide bonds with prolyl P1 specificities (but cleavage of alanyl bonds has been detected). The proline must adopt a trans configuration within the chain. Peptides of up to 30 residues are cleaved [].
Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes [
]. They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence []. Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases [].Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base [
]. The geometric orientations of the catalytic residues are similar between families, despite different protein folds []. The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) [,
].This domain covers the active site serine of the serine peptidases belonging to MEROPS peptidase family S9 (prolyl oligopeptidase family, clan SC). The protein fold of the peptidase domain for members of this family resembles that of serine carboxypeptidase D, the type example of clan SC.
Examples of protein families containing this domain are:Prolyl endopeptidase (
) (PE) (also called post-proline cleaving
enzyme). PE is an enzyme that cleaves peptide bonds on the C-terminal sideof prolyl residues. The sequence of PE has been obtained from a mammalian
species (pig) and from bacteria (Flavobacterium meningosepticum andAeromonas hydrophila); there is a high degree of sequence conservation
between these sequences.Escherichia coli protease II (
) (oligopeptidase B) (gene prtB)
which cleaves peptide bonds on the C-terminal side of lysyl and argininylresidues.
Dipeptidyl peptidase IV (
) (DPP IV). DPP IV is an enzyme that
removes N-terminal dipeptides sequentially from polypeptides havingunsubstituted N-termini provided that the penultimate residue is proline.
Saccharomyces cerevisiae (Baker's yeast) vacuolar dipeptidyl aminopeptidases A and B (DPAP A and DPAP B), encoded by the STE13 and DAP2 genes respectively. DPAP A is responsible for the proteolytic maturation of the alpha-factor precursor.Acylamino-acid-releasing enzyme (
) (acyl-peptide hydrolase).
This enzyme catalyses the hydrolysis of the amino-terminal peptide bond ofan N-acetylated protein to generate a N-acetylated amino acid and a protein
with a free amino-terminus.These proteins belong to MEROPS peptidase families S9A, S9B and S9C.
Members of this family are integral membrane proteins. This family includes a protein with hemolytic activity from Bacillus cereus [
]. YOL002c (AdipoR-like receptor IZH2) from Saccharomyces cerevisiae encodes a protein that plays a key role in metabolic pathways that regulate lipid and phosphate metabolism [
,
]. In eukaryotes, members are seven-transmembrane pass molecules found to encode functional receptors with a broad range of apparent ligand specificities, including progestin and adiponectin (AdipoQ) receptors (AdipoR), and hence have been named PAQR proteins []. The mammalian members include progesterone binding proteins []. Unlike the case with GPCR receptor proteins, the evolutionary ancestry of the members of this family can be traced back to the Archaea.
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 [
,
].L35 is a basic protein of 60 to 70 amino-acid residues from the large subunit [
]. Like many basic polypeptides, L35 completely inhibits ornithine decarboxylase when present unbound in the cell, but the inhibitory function is abolished upon its incorporation into ribosomes []. It belongs to a family of ribosomal proteins, including L35 from bacteria, plant chloroplast, red algae chloroplasts and cyanelles. In plants it is a nuclear encoded gene product, which suggests a chloroplast-to-nucleus relocation during the evolution of higher plants [].
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 [
,
].L35 is a basic protein of 60 to 70 amino-acid residues from the large subunit [
]. Like many basic polypeptides, L35 completely inhibits ornithine decarboxylase when present unbound in the cell, but the inhibitory function is abolished upon its incorporation into ribosomes []. It belongs to a family of ribosomal proteins, including L35 from bacteria, plant chloroplast, red algae chloroplasts and cyanelles. In plants it is a nuclear encoded gene product, which suggests a chloroplast-to-nucleus relocation during the evolution of higher plants [].
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 [
,
].L35 is a basic protein of 60 to 70 amino-acid residues from the large subunit [
]. Like many basic polypeptides, L35 completely inhibits ornithine decarboxylase when present unbound in the cell, but the inhibitory function is abolished upon its incorporation into ribosomes []. It belongs to a family of ribosomal proteins, including L35 from bacteria, plant chloroplast, red algae chloroplasts and cyanelles. In plants it is a nuclear encoded gene product, which suggests a chloroplast-to-nucleus relocation during the evolution of higher plants [
].This entry represents a conserved region in the N-terminal section of L35.
This family includes SRP-independent targeting protein 2 (SND2) from yeast and transmembrane protein 208 (TMEM208) from mammals. Both are localized to the endoplasmic reticulum (ER) [
,
]. SND2 works together with SND1 and SND3 in an alternative targeting route to the ER []. TMEM208 regulates both ER stress and autophagy [].SND2 was previously known as Env10 in Saccharomyces cerevisiae, and its homologue as Mug69 in Schizosaccharomyces pombe. They were identified as proteins involved in vacuolar processing and morphology [
] and meiosis [], respectively.
The HD domain is found in a superfamily of enzymes with a predicted or known phosphohydrolase activity [
]. These enzymes appear to be involved in the nucleic acid metabolism, signal transduction and possibly other functions in bacteria, archaea and eukaryotes.The fact that all the highly conserved residues in the HD superfamily are histidines or aspartates suggests that coordination of divalent cations is essential for the activity of these proteins [
].
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 riboflavin kinase, which occurs as part of a bifunctional enzyme or a stand-alone enzyme.
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 the riboflavin kinase domains from bacteria and eukaryotes.
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 riboflavin kinase, which occurs as part of a bifunctional enzyme or a stand-alone enzyme.
The anaphase-promoting complex (APC) or cyclosome is a multi-subunit E3 protein ubiquitin ligase that regulates important events in mitosis, such as the initiation of anaphase and exit from telophase. The APC, in conjunction with other enzymes, assembles multi-ubiquitin chains on a variety of regulatory proteins, thereby targeting them for proteolysis by the 26S proteasome [
].This family represents the anaphase-promoting complex subunit 4 (APC4). This entry also includes APC4 homologue, EMB-30, from Caenorhabditis elegans [
].
Apc4 is one of the larger of the subunits of the anaphase-promoting complex (APC) or cyclosome. The anaphase-promoting complex is a multiprotein subunit E3 ubiquitin ligase complex that controls segregation of chromosomes and exit from mitosis in eukaryotes [
,
]. Results in Caenorhabditis elegans show that the primary essential role of the spindle assembly checkpoint is not in the chromosome segregation process itself but rather in delaying anaphase onset until all chromosomes are properly attached to the spindle. The APC is likely to be required for all metaphase-to-anaphase transitions in a multicellular organism [].This entry represents the long domain downstream of the WD40 repeat/s that are present on the Apc4 subunits.
Vacuolar protein sorting-associated, VPS28, N-terminal
Type:
Domain
Description:
The Endosomal Sorting Complex Required for Transport (ESCRT) complexes form the machinery driving protein sorting from endosomes to lysosomes. ESCRT complexes are central to receptor down-regulation, lysosome biogenesis, and budding of HIV. Yeast ESCRT-I consists of three protein subunits, Vps23, Vps28, and Vps37. In humans, ESCRT-I comprises TSG101, VPS28, and one of four potential human VPS37 homologues. The main role of ESCRT-I is to recognise ubiquitinated cargo via the UEV domain of the VPS23/TSG101 subunit. The assembly of the ESCRT-I complex is directed by the C-terminal steadiness box (SB) of VPS23, the N-terminal half of VPS28, and the C-terminal half of VPS37. The structure is primarily composed of three long, parallel helical hairpins, each corresponding to a different subunit. The additional domains and motifs extending beyond the core serve as gripping tools for ESCRT-I critical functions [,
].This entry represents the N-terminal domain of VPS28.
The Endosomal Sorting Complex Required for Transport (ESCRT) complexes form the machinery driving protein sorting from endosomes to lysosomes. ESCRT complexes are central to receptor down-regulation, lysosome biogenesis, and budding of HIV. Yeast ESCRT-I consists of three protein subunits, Vps23, Vps28, and Vps37. In humans, ESCRT-I comprises TSG101, VPS28, and one of four potential human VPS37 homologues. The main role of ESCRT-I is to recognise ubiquitinated cargo via the UEV domain of the VPS23/TSG101 subunit. The assembly of the ESCRT-I complex is directed by the C-terminal steadiness box (SB) of VPS23, the N-terminal half of VPS28, and the C-terminal half of VPS37. The structure is primarily composed of three long, parallel helical hairpins, each corresponding to a different subunit. The additional domains and motifs extending beyond the core serve as gripping tools for ESCRT-I critical functions [
,
].
Vacuolar protein sorting-associated, VPS28, C-terminal
Type:
Domain
Description:
The Endosomal Sorting Complex Required for Transport (ESCRT) complexes form the machinery driving protein sorting from endosomes to lysosomes. ESCRT complexes are central to receptor down-regulation, lysosome biogenesis, and budding of HIV. Yeast ESCRT-I consists of three protein subunits, Vps23, Vps28, and Vps37. In humans, ESCRT-I comprises TSG101, VPS28, and one of four potential human VPS37 homologues. The main role of ESCRT-I is to recognise ubiquitinated cargo via the UEV domain of the VPS23/TSG101 subunit. The assembly of the ESCRT-I complex is directed by the C-terminal steadiness box (SB) of VPS23, the N-terminal half of VPS28, and the C-terminal half of VPS37. The structure is primarily composed of three long, parallel helical hairpins, each corresponding to a different subunit. The additional domains and motifs extending beyond the core serve as gripping tools for ESCRT-I critical functions [
,
].This entry represents the C-terminal domain of VPS28.
Prefoldin (PFD) is a chaperone that interacts exclusively with type II chaperonins, hetero-oligomers lacking an obligate co-chaperonin that are found only in eukaryotes (chaperonin-containing T-complex polypeptide-1 (CCT)) and archaea. Eukaryotic PFD is a multi-subunit complex containing six polypeptides in the molecular mass range of 14-23kDa. In archaea, on the other hand, PFD is composed of two types of subunits, two alpha and four beta. The six subunits associate to form two back-to-back up-and-down eight-stranded barrels, from which hang six coiled coils. Each subunit contributes one (beta subunits) or two (alpha subunits) beta hairpin turns to the barrels. The coiled coils are formed by the N and C termini of an individual subunit. Overall, this unique arrangement resembles a jellyfish. The eukaryotic PFD hexamer is composed of six different subunits; however, these can be grouped into two alpha-like (PFD3 and -5) and four beta-like (PFD1, -2, -4, and -6) subunits based on amino acid sequence similarity with their archaeal counterparts. Eukaryotic PFD has a six-legged structure similar to that seen in the archaeal homologue [
,
].This entry represents the archaeal alpha subunit and the closely related eukaryotic subunit 5.
Anthranilate synthase catalyses the first step in the biosynthesis of tryptophan. Component I catalyses the formation of anthranilate using ammonia and chorismate. The catalytic site lies in the adjacent region, described in the chorismate binding enzyme family (
). This region is involved in feedback inhibition by tryptophan [
]. This family also contains a region of Para-aminobenzoate synthase component I.
This enzyme resembles some other chorismate-binding enzymes, including para-aminobenzoate synthase (pabB) and isochorismate synthase. There is a fairly deep split between two sets, seen in the pattern of gaps as well as in amino acid sequence differences. This group includes eukaryotes, archaea, and many bacterial lineages; sequences from the second group may resemble pabB more closely than other trpE from the other group. The other group includes Gram-negative proteobacteria such as Escherichia coli and Helicobacter pylori but also the Gram-positive organism Corynebacterium glutamicum, and is described by
.
A sequence from Bacillus subtilis that scores above the trusted cut-off is annotated as PabB rather than TrpE. However, it is part of an operon that is required for Trp as well as folate biosynthesis, is Trp-repressible, and contains TrpG. It is likely that this sequence annotated as PabB functions both as PabB and as TrpE.
This entry represents the anthranilate synthase component 1 protein
and its homologues, including aminodeoxychorismate synthase component 1
, 2-amino-4-deoxychorismate synthase
and isochorismate synthase/isochorismate-pyruvate lyase MbtI
.
Anthranilate synthase component 1 is a tetramer comprising two copies of component I and two copies of component II. Component I catalyses the formation of anthranilate using ammonia rather than glutamine, while component II provides glutamine amidotransferase activity.
These peptidases have gamma-glutamyl hydrolase activity; that is they catalyse the cleavage of the gamma-glutamyl bond in poly-gamma-glutamyl substrates. They are structurally related to
, but contain extensions in four loops and at the C terminus [
]. They belong to MEROPS peptidase family C26 (gamma-glutamyl hydrolase family), clan PC. The majority of the sequences are classified as unassigned peptidases. A cysteine peptidase is a proteolytic enzyme that hydrolyses a peptide bond using the thiol group of a cysteine residue as a nucleophile. Hydrolysis involves usually a catalytic triad consisting of the thiol group of the cysteine, the imidazolium ring of a histidine, and a third residue, usually asparagine or aspartic acid, to orientate and activate the imidazolium ring. In only one family of cysteine peptidases, is the role of the general base assigned to a residue other than a histidine: in peptidases from family C89 (acid ceramidase) an arginine is the general base. Cysteine peptidases can be grouped into fourteen different clans, with members of each clan possessing a tertiary fold unique to the clan. Four clans of cysteine peptidases share structural similarities with serine and threonine peptidases and asparagine lyases. From sequence similarities, cysteine peptidases can be clustered into over 80 different families []. Clans CF, CM, CN, CO, CP and PD contain only one family.Cysteine peptidases are often active at acidic pH and are therefore confined to acidic environments, such as the animal lysosome or plant vacuole. Cysteine peptidases can be endopeptidases, aminopeptidases, carboxypeptidases, dipeptidyl-peptidases or omega-peptidases. They are inhibited by thiol chelators such as iodoacetate, iodoacetic acid,
N-ethylmaleimide or
p-chloromercuribenzoate.
Clan CA includes proteins with a papain-like fold. There is a catalytic triad which occurs in the order: Cys/His/Asn (or Asp). A fourth residue, usually Gln, is important for stabilising the acyl intermediate that forms during catalysis, and this precedes the active site Cys. The fold consists of two subdomains with the active site between them. One subdomain consists of a bundle of helices, with the catalytic Cys at the end of one of them, and the other subdomain is a β-barrel with the active site His and Asn (or Asp). There are over thirty families in the clan, and tertiary structures have been solved for members of most of these. Peptidases in clan CA are usually sensitive to the small molecule inhibitor E64, which is ineffective against peptidases from other clans of cysteine peptidases [
].Clan CD includes proteins with a caspase-like fold. Proteins in the clan have an α/β/α sandwich structure. There is a catalytic dyad which occurs in the order His/Cys. The active site His occurs in a His-Gly motif and the active site Cys occurs in an Ala-Cys motif; both motifs are preceded by a block of hydrophobic residues [
]. Specificity is predominantly directed towards residues that occupy the S1 binding pocket, so that caspases cleave aspartyl bonds, legumains cleave asparaginyl bonds, and gingipains cleave lysyl or arginyl bonds.Clan CE includes proteins with an adenain-like fold. The fold consists of two subdomains with the active site between them. One domain is a bundle of helices, and the other a β-barrel. The subdomains are in the opposite order to those found in peptidases from clan CA, and this is reflected in the order of active site residues: His/Asn/Gln/Cys. This has prompted speculation that proteins in clans CA and CE are related, and that members of one clan are derived from a circular permutation of the structure of the other.Clan CL includes proteins with a sortase B-like fold. Peptidases in the clan hydrolyse and transfer bacterial cell wall peptides. The fold shows a closed β-barrel decorated with helices with the active site at one end of the barrel [
]. The active site consists of a His/Cys catalytic dyad.Cysteine peptidases with a chymotrypsin-like fold are included in clan PA, which also includes serine peptidases. Cysteine peptidases that are N-terminal nucleophile hydrolases are included in clan PB. Cysteine peptidases with a tertiary structure similar to that of the serine-type aspartyl dipeptidase are included in clan PC. Cysteine peptidases with an intein-like fold are included in clan PD, which also includes asparagine lyases.
NADH-plastoquinone oxidoreductase subunit I (
) catalyses the conversion of plastoquinone and NADH to plastoquinol and NAD(+). The enzyme binds two 4FE-4S clusters at iron-sulphur centres which are similar to those of the bacterial-type 4FE-4S ferredoxins.
NADH:ubiquinone oxidoreductase, subunit 1/F420H2 oxidoreductase subunit H
Type:
Family
Description:
NADH:ubiquinone oxidoreductase (complex I) (
) is a respiratory-chain enzyme that catalyses the transfer of two electrons from NADH to ubiquinone in a reaction that is associated with proton translocation across the membrane (NADH + ubiquinone = NAD+ + ubiquinol) [
]. Complex I is a major source of reactive oxygen species (ROS) that are predominantly formed by electron transfer from FMNH(2). Complex I is found in bacteria, cyanobacteria (as a NADH-plastoquinone oxidoreductase), archaea [], mitochondria, and in the hydrogenosome, a mitochondria-derived organelle. In general, the bacterial complex consists of 14 different subunits, while the mitochondrial complex contains homologues to these subunits in addition to approximately 31 additional proteins [].This entry represents subunit 1 NADH:ubiquinone oxidoreductase [
]. Among the many polypeptide subunits that make up complex I, there are fifteen which are located in the membrane part, seven of which are encoded by the mitochondrial and chloroplast genomes of most species. The most conserved of these organelle-encoded subunits is known as subunit 1 (gene ND1 in mitochondrion, and NDH1 in chloroplast) and seems to contain the ubiquinone binding site.The ND1 subunit is highly similar to subunit 4 of Escherichia coli formate hydrogenlyase (gene hycD), subunit C of hydrogenase-4 (gene hyfC). Paracoccus denitrificans NQO8 and Escherichia coli nuoH NADH-ubiquinone oxidoreductase subunits also belong to this family [
].This entry also includes the archaeal F420H2 oxidoreductase subunit H (FPO). FPO shuttles electrons from F420H2, via FAD and iron-sulphur (Fe-S) centres, to quinones in the F420H2:heterodisulphide oxidoreduction chain. The immediate electron acceptor for the enzyme in this species is believed to be methanophenazine. Couples the redox reaction to proton translocation (for every two electrons transferred, 0.9 hydrogen ions are translocated across the cytoplasmic membrane), and thus conserves the redox energy in a proton gradient.
NADH:ubiquinone oxidoreductase, subunit 1, conserved site
Type:
Conserved_site
Description:
NADH:ubiquinone oxidoreductase (complex I) (
) is a respiratory-chain enzyme that catalyses the transfer of two electrons from NADH to ubiquinone in a reaction that is associated with proton translocation across the membrane (NADH + ubiquinone = NAD+ + ubiquinol) [
]. Complex I is a major source of reactive oxygen species (ROS) that are predominantly formed by electron transfer from FMNH(2). Complex I is found in bacteria, cyanobacteria (as a NADH-plastoquinone oxidoreductase), archaea [], mitochondria, and in the hydrogenosome, a mitochondria-derived organelle. In general, the bacterial complex consists of 14 different subunits, while the mitochondrial complex contains homologues to these subunits in addition to approximately 31 additional proteins [].This entry represents subunit 1 NADH:ubiquinone oxidoreductase [
]. Among the many polypeptide subunits that make up complex I, there are fifteen which are located in the membrane part, seven of which are encoded by the mitochondrial and chloroplast genomes of most species. The most conserved of these organelle-encoded subunits is known as subunit 1 (gene ND1 in mitochondrion, and NDH1 in chloroplast) and seems to contain the ubiquinone binding site.The ND1 subunit is highly similar to subunit 4 of Escherichia coli formate hydrogenlyase (gene hycD), subunit C of hydrogenase-4 (gene hyfC). Paracoccus denitrificans NQO8 and Escherichia coli nuoH NADH-ubiquinone oxidoreductase subunits also belong to this family [
].
The CcsA protein family represents one of two essential proteins in system II c-type cytochrome biogenesis [
]. Additional proteins tend to be part of the system but can often be replaced by chemical reductants such as dithiothreitol. These proteins are often named CcsB in Bordetella and some other bacteria, ResC in Bacillus (where there is additional N-terminal sequence), while chloroplast proteins are consistently named CcsA.
This domain is found in various proteins involved in cytochrome c
assembly from mitochondria, chloroplast and bacteria; including among others CycK from Rhizobium leguminosarum [], CcmC and CcmF from Escherichia coli [], CcsA from Chlamydomonas [], and orf240 from Triticum aestivum (wheat) mitochondria [].CcmC interacts directly with heme, and it is the only protein of the ccm operon that is strictly required for heme transfer [
]. CcmF contains a b-type heme and is thought to be a cytochrome c synthetase []. CcsA is required during biogenesis of c-type cytochromes at the step of heme attachment []. R. leguminosarum CycK and wheat orf240 also contain a putative heme-binding motif [,
].
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 S3 is one of the proteins from the small ribosomal subunit. In
Escherichia coli, S3 is known to be involved in the binding of initiator Met-tRNA. This family of ribosomal proteins includes S3 from bacteria, algae and plant chloroplast, cyanelle, archaebacteria, plant mitochondria, vertebrates, insects,
Caenorhabditis elegans and yeast []. This entry is the C-terminal domain.
The K homology domain is a common RNA-binding motif present in one or multiple copies in both prokaryotic and eukaryotic regulatory proteins. The KH motifs may act cooperatively to bind RNA in the case of multiple motifs, or independently in the case of single KH motif proteins. Prokaryotic (pKH) and eukaryotic (eKH) KH domains share a KH-motif, but have different topologies. The pKH domain has been found in a number of proteins, including the N-terminal domain of the S3 ribosomal protein [
], the C-terminal domain of Era GTPase [] and the two C-terminal domains of the NusA transcription factor []. The structure of the pKH domain consists of a two-layer α/β fold in the arrangement α/β(2)/α/β.
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 S3 is one of the proteins from the small ribosomal subunit.
This family describes the bacterial type of ribosomal protein S3 and also and many chloroplast forms. Chloroplast and mitochondrial forms have large, variable inserts between conserved N-terminal and C-terminal domains.
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 S3 is one of the proteins from the small ribosomal subunit. In
Escherichia coli, S3 is known to be involved in the binding of initiator Met-tRNA. This family of ribosomal proteins includes S3 from bacteria, algae and plant chloroplast, cyanelle, archaebacteria, plant mitochondria, vertebrates, insects,
Caenorhabditis elegans and yeast []. This entry is the C-terminal domain.
In the mitochondrion of eukaryotes and in aerobic prokaryotes, cytochrome b is a component of respiratory chain complex III (
) - also known as the bc1 complex or ubiquinol-cytochrome c reductase. In plant chloroplasts and cyanobacteria, there is a analogous protein, cytochrome b6, a component of the plastoquinone-plastocyanin reductase (
), also known as the b6f complex.
Cytochrome b/b6 [
,
] is an integral membrane protein of approximately 400 amino acid residues that probably has 8 transmembrane segments. In plants and cyanobacteria, cytochrome b6 consists of two subunits encoded by the petB and petD genes. The sequence of petB is colinear with the N-terminal part of mitochondrial cytochrome b, while petD corresponds to the C-terminal part.Cytochrome b/b6 non-covalently binds two haem groups, known as b562 and b566. Four conserved histidine residues are postulated to be the ligands of the iron atoms of these two haem groups.
Apart from regions around some of the histidine haem ligands, there are a few conserved regions in the sequence of b/b6. The best conserved of these regions includes an invariant P-E-W triplet which lies in the loop that separates the fifth and sixth transmembrane segments. It seems to be important for electron transfer at the ubiquinone redox site - called Qz or Qo (where o stands for outside) - located on the outer side of the membrane. This entry is the C terminus of these proteins.
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 [
,
].This entry represents the bacterial and organellar branch of the ribosomal protein S7 family.
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 [
,
].This entry represents 30S ribosomal proteins S7 (bacterial, archaeal, plastid, mitochondrial), and eukaryotic 40S ribosomal proteins S5 (cytoplasmic). 30S ribosomal protein S7 contacts ribosomal proteins S9 and S11. It is also one of the primary rRNA binding proteins - it binds directly to 16S rRNA - where it nucleates assembly of the head domain of the 30S subunit [
]. S7 is located at the subunit interface close to the decoding centre, where it has been shown to contact mRNA. It has also been shown to contact tRNA in both the P and E sites; it probably blocks exit of the E site tRNA.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].Ribosomal protein S7 is one of the proteins from the small ribosomal subunit.
In Escherichia coli, S7 is known to bind directly to part of the 3'end of 16Sribosomal RNA. It belongs to a family of ribosomal proteins which have been grouped on the
basis of sequence similarities [,
].This entry represents the S7 structural domain, which consists of a bundle of six helices and an extended beta hairpin between helices 3 and 4, with two or more RNA-binding sites on its surface [
].
NADH:ubiquinone oxidoreductase, 49kDa subunit, conserved site
Type:
Conserved_site
Description:
NADH:ubiquinone oxidoreductase (complex I) (
) is a respiratory-chain enzyme that catalyses the transfer of two electrons from NADH to ubiquinone in a reaction that is associated with proton translocation across the membrane (NADH + ubiquinone = NAD+ + ubiquinol) [
]. Complex I is a major source of reactive oxygen species (ROS) that are predominantly formed by electron transfer from FMNH(2). Complex I is found in bacteria, cyanobacteria (as a NADH-plastoquinone oxidoreductase), archaea [], mitochondria, and in the hydrogenosome, a mitochondria-derived organelle. In general, the bacterial complex consists of 14 different subunits, while the mitochondrial complex contains homologues to these subunits in addition to approximately 31 additional proteins [].This entry represents a highly conserved region found towards the N terminus of the 49kDa subunit of NADH:ubiquinone oxidoreductase.
Saccharomyces cerevisiaeEfm4 (also known as See1) is a lysine methyltransferase that dimethylates eukaryotic elongation factor 1A (eEF1A1) at lysine residues [
]. It may also play a role in intracellular transport []. This entry also includes methyltransferase-like protein 10 (METTL10; EEF1A lysine methyltransferase 2) from fish and mammals, which catalyzes the trimethylation of EEF1A at 'Lys-318' [].
Rho guanosine triphosphatases (GTPases) are critical regulators of cell motility, polarity, adhesion, cytoskeletal organisation, proliferation, gene
expression, and apoptosis. Conversion of these biomolecular switches to the activated GTP-bound state is controlled by two families of guanine nucleotide exchanges factors (GEFs). DH-PH proteins are a large group of Rho GEFs comprising a catalytic Dbl homology (DH) domain with anadjacent pleckstrin homology (PH) domain within the context of functionally diverse signalling modules. The evolutionarily distinct and smaller family of DOCK (dedicator of cytokinesis) or CDM (CED-5, DOCK1180, Myoblast city) proteins activate either Rac or Cdc42 to control cell migration, morphogenesis, and phagocytosis. DOCK proteins share the DOCK-type C2 domain (also termed the DOCK-homology region (DHR)-1 or CDM-zizimin homology 1 (CZH1) domain and the DOCKER domain (also termed the DHR-2 or CZH2 domain) [
,
,
,
,
,
,
].The DOCK-type C2 domain is located toward the N terminus [
]. The DOCKER domain is a GEF catalytic domain of ~400 residues situated within the C terminus. The structure of the DOCKER domain differs from that of other GEF catalytic domains. It is organised into three lobes of roughly equal size (lobes A, B, and C), with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. Lobe A is formed from an antiparallel array of alpha helices. Through extensive contacts with lobe B, lobe A stabilises the DHR2 domain. Lobe B adopts an unusual architecture of two antiparallel beta sheets disposed in a loosely packed orthogonal arrangement, whereas lobe C comprises a four-helix bundle [,
].This entry represents the DOCKER domain.
Aminoacyl-tRNA synthetases (aaRSs) play a crucial role in the translation of the genetic code by means of covalent attachment of amino acids to their
cognate tRNAs. Phenylalanine-tRNA synthetase (PheRS, also known as Phenylalanine-tRNA ligase) is known to be among themost complex enzymes of the aaRS family. Bacterial and mitochondrial PheRSs
share a ferredoxin-fold anticodon binding (FDX-ACB) domain, which represents acanonical double split alpha+beta motif having no insertions. The FDX-ACB
domain displays a typical RNA recognition fold (RRM) (see ) formed by the four-stranded antiparallel beta sheet, with two helices packed against it [
,
,
,
,
].
Phenylalanyl-tRNA synthetase, class IIc, mitochondrial
Type:
Family
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 [].Phenylalanyl-tRNA synthetase (
) is an alpha2/beta2 tetramer composed of 2 subunits that belongs to class IIc. In eubacteria, a small subunit (pheS gene) can be designated as beta (E. coli) or alpha subunit (nomenclature adopted in InterPro). Reciprocally the large subunit
(pheT gene) can be designated as alpha (E. coli) or beta (see and
). In all other kingdoms the two subunits have equivalent length in eukaryota, and can be identified by specific signatures. The enzyme from Thermus thermophilus has an alpha 2 beta 2 type quaternary structure and is one of the most complicated members of the synthetase family. Identification of phenylalanyl-tRNA synthetase as a member of class II aaRSs was based only on sequence alignment of the small alpha-subunit with other synthetases [
].This family describes the mitochondrial phenylalanyl-tRNA synthetases. Unlike all other known phenylalanyl-tRNA synthetases, the mitochondrial form demonstrated from yeast is monomeric. It is similar to but longer than the alpha subunit (PheS) of the alpha 2 beta 2 form found in bacteria, Archaea, and eukaryotes, and shares the characteristic motifs of class II aminoacyl-tRNA ligases.
Crustacean and cheliceratan hemocyanins (oxygen-transport proteins) and insect hexamerins (storage proteins) are homologous gene products, although the latter do not bind oxygen [
].Haemocyanins are found in the haemolymph of many invertebrates. They are divided into 2 main groups, arthropodan and molluscan. These have structurally similar oxygen-binding centres, which are similar to the oxygen-binding centre of tyrosinases, but their quaternary structures are arranged differently. The arthropodan proteins exist as hexamers comprising 3 heterogeneous subunits (a, b and c) and possess 1 oxygen-binding centre per subunit; and the molluscan proteins exist as cylindrical oligomers of 10 to 20 subunits and possess 7 or 8 oxygen-binding centres per subunit [
]. Although the proteins have similar amino acid compositions, the only real similarity in their primary sequences is in the region corresponding to the second copper-binding domain, which also shows similarity to the copper-binding domain of tyrosinases. Hexamerins are proteins from the hemolymph of insects, which may serve as a store of amino acids for synthesis of adult proteins. They do not possess the copper-binding histidines present in hemocyanins [
]. Homologues are also present in other kinds of organism, for example, Cyclopenase asqI from the yeast Emericella nidulans and Cyclopenase penL from Penicillium thymicola. AsqL is a tyrosinase involved in biosynthesis of the aspoquinolone mycotoxins, though its exact function is unknown [
]. PenL is part of the gene cluster that mediates the biosynthesis of penigequinolones, potent insecticidal alkaloids that contain a highly modified 10-carbon prenyl group [].
This entry represents RBM39 (also known as CAPER) proteins from mammals and a group of putative RNA splicing factors including the Pad1 protein from fungi. All are characterised by an N-terminal arginine-rich, low complexity domain followed by three (or in the case of 4 human paralogs, two) RNA recognition domains. These proteins are closely related to the U2AF splicing factor family (
).
In mice, CAPER is a transcriptional coactivator of activating protein-1 (AP-1) and estrogen receptors (ERs) [
]. It may be involved in pre-mRNA splicing process.
NADH:ubiquinone oxidoreductase (complex I) (
) is a respiratory-chain enzyme that catalyses the transfer of two electrons from NADH to ubiquinone in a reaction that is associated with proton translocation across the membrane (NADH + ubiquinone = NAD+ + ubiquinol) [
]. Complex I is a major source of reactive oxygen species (ROS) that are predominantly formed by electron transfer from FMNH(2). Complex I is found in bacteria, cyanobacteria (as a NADH-plastoquinone oxidoreductase), archaea [
], mitochondria, and in the hydrogenosome, a mitochondria-derived organelle. In general, the bacterial complex consists of 14 different subunits, while the mitochondrial complex contains homologues to these subunits in addition to approximately 31 additional proteins [].This family consists of the accessory subunit of complex I NADH-ubiquinone oxidoreductase NDUB7 (or NDUFB7, also known as B18), which is not involved in catalysis [
,
].
This domain is found in various cobyrinic acid a,c-diamide synthases. These include CbiA
() and CbiP (
) from S. typhimurium [
], and CobQ () from R. capsulatus [
]. These amidases catalyse amidations to various side chains of hydrogenobyrinic acid or cobyrinic acid a,c-diamide in the biosynthesis of cobalamin (vitamin B12) from uroporphyrinogen III. Vitamin B12 is an important cofactor and an essential nutrient for many plants and animals and is primarily produced by bacteria []. The domain is also found in dethiobiotin synthetases as well as the plasmid partitioning proteins of the MinD/ParA family [
].
Rtf2 is a replication termination factor which mediates replication termination at the site-specific replication barrier Rts1. It stabilizes the replication fork stalled at Rts1 until completion of DNA synthesis by a converging replication fork initiated at a flanking origin [
].
It is vital for effective cell-replication that replication is not stalled at any point by, for instance, damaged bases. Replication termination factor 2 (Rtf2) stabilises the replication fork stalled at the site-specific replication barrier RTS1 by preventing replication restart until completion of DNA synthesis by a converging replication fork initiated at a flanking origin. The RTS1 element terminates replication forks that are moving in the cen2-distal direction while allowing forks moving in the cen2-proximal direction to pass through the region. Rtf2 contains a C2HC2 motif related to the C3HC4 RING-finger motif, and would appear to fold up, creating a RING finger-like structure but forming only one functional Zn2+ ion-binding site [
].
The majority of members of this family are zinc-dependent exopeptidases belonging to MEROPS peptidase family M17 (leucyl aminopeptidase, clan MF).This family excludes pepB aminopeptidases, which are also members of MEROPS family M17 (see
).
Leucyl aminopeptidase (LAP;
) selectively release N-terminal amino acid residues from polypeptides and proteins; in general they are involved in the processing, catabolism and degradation of intracellular proteins [
,
,
]. Leucyl aminopeptidase forms a homohexamer containing two trimers stacked on top of one another []. Each monomer binds two zinc ions. The zinc-binding and catalytic sites are located within the C-terminal catalytic domain []. Leucine aminopeptidase has been shown to be identical with prolyl aminopeptidase () in mammals [
]. Interestingly, members of this group are also implicated in transcriptional regulation and are thought to combine catalytic and regulatory properties [
]. The N-terminal domain of these proteins has been shown in Escherichia coli PepA to function as a DNA-binding protein in Xer site-specific recombination and in transcriptional control of the carAB operon [,
]. It is not well conserved and in some members can be found only by PSI-BLAST (after 4-6 iterations). It is not clear if the DNA binding function is preserved in all or even in most of the members.For additional information please see [
,
,
,
].
Signal recognition particle, SRP54 subunit, GTPase domain
Type:
Domain
Description:
The signal recognition particle (SRP) is a multimeric protein, which along with its conjugate receptor (SR), is involved in targeting secretory proteins to the rough endoplasmic reticulum (RER) membrane in eukaryotes, or to the plasma membrane in prokaryotes [
,
]. SRP recognises the signal sequence of the nascent polypeptide on the ribosome. In eukaryotes this retards its elongation until SRP docks the ribosome-polypeptide complex to the RER membrane via the SR receptor []. Eukaryotic SRP consists of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72) and a single 300 nucleotide 7S RNA molecule. The RNA component catalyses the interaction of SRP with its SR receptor []. In higher eukaryotes, the SRP complex consists of the Alu domain and the S domain linked by the SRP RNA. The Alu domain consists of a heterodimer of SRP9 and SRP14 bound to the 5' and 3' terminal sequences of SRP RNA. This domain is necessary for retarding the elongation of the nascent polypeptide chain, which gives SRP time to dock the ribosome-polypeptide complex to the RER membrane. In archaea, the SRP complex contains 7S RNA like its eukaryotic counterpart, yet only includes two of the six protein subunits found in the eukarytic complex: SRP19 and SRP54 [].This entry represents the GTPase domain of the 54kDa SRP54 component, a GTP-binding protein that interacts with the signal sequence when it emerges from the ribosome. SRP54 of the signal recognition particle has a three-domain structure: an N-terminal helical bundle domain, a GTPase domain, and the M-domain that binds the 7s RNA and also binds the signal sequence. The extreme C-terminal region is glycine-rich and lower in complexity and poorly conserved between species. The GTPase domain is evolutionary related to P-loop NTPase domains found in a variety of other proteins [
].These proteins include Escherichia coli and Bacillus subtilis ffh protein (P48), which seems to be the prokaryotic counterpart of SRP54; signal recognition particle receptor alpha subunit (docking protein), an integral membrane GTP-binding protein which ensures, in conjunction with SRP, the correct targeting of nascent secretory proteins to the endoplasmic reticulum membrane; bacterial FtsY protein, which is believed to play a similar role to that of the docking protein in eukaryotes; the pilA protein from Neisseria gonorrhoeae, the homologue of ftsY; and bacterial flagellar biosynthesis protein flhF.
Signal recognition particle receptor, alpha subunit, N-terminal
Type:
Domain
Description:
The signal recognition particle (SRP) is a multimeric protein, which along with its conjugate receptor (SR), is involved in targeting secretory proteins to the rough endoplasmic reticulum (RER) membrane in eukaryotes, or to the plasma membrane in prokaryotes [
,
]. SRP recognises the signal sequence of the nascent polypeptide on the ribosome. In eukaryotes this retards its elongation until SRP docks the ribosome-polypeptide complex to the RER membrane via the SR receptor []. Eukaryotic SRP consists of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72) and a single 300 nucleotide 7S RNA molecule. The RNA component catalyses the interaction of SRP with its SR receptor []. In higher eukaryotes, the SRP complex consists of the Alu domain and the S domain linked by the SRP RNA. The Alu domain consists of a heterodimer of SRP9 and SRP14 bound to the 5' and 3' terminal sequences of SRP RNA. This domain is necessary for retarding the elongation of the nascent polypeptide chain, which gives SRPtime to dock the ribosome-polypeptide complex to the RER membrane. In archaea, the SRP complex contains 7S RNA like its eukaryotic counterpart, yet only includes two of the six protein subunits found in the eukarytic complex: SRP19 and SRP54 [
].The SR receptor is a monomer consisting of the loosely membrane-associated SR-alpha homologue FtsY, while the eukaryotic SR receptor is a heterodimer of SR-alpha (70kDa) and SR-beta (25kDa), both of which contain a GTP-binding domain [
]. SR-alpha regulates the targeting of SRP-ribosome-nascent polypeptide complexes to the translocon []. SR-alpha binds to the SRP54 subunit of the SRP complex. The SR-beta subunit is a transmembrane GTPase that anchors the SR-alpha subunit (a peripheral membrane GTPase) to the ER membrane []. SR-beta interacts with the N-terminal SRX-domain of SR-alpha, which is not present in the bacterial FtsY homologue. SR-beta also functions in recruiting the SRP-nascent polypeptide to the protein-conducting channel. This entry represents the alpha subunit of the SR receptor.
This entry represents the N-terminal helical bundle domain of the 54kDa SRP54 component, a GTP-binding protein that interacts with the signal sequence when it emerges from the ribosome. SRP54 of the signal recognition particle has a three-domain structure: an N-terminal helical bundle domain, a GTPase domain, and the M-domain that binds the 7s RNA and also binds the signal sequence. The extreme C-terminal region is glycine-rich and lower in complexity and poorly conserved between species.Other proteins with this domain include signal recognition particle receptor alpha subunit (docking protein), an integral membrane GTP-binding protein which ensures (in conjunction with SRP) the correct targeting of nascent secretory proteins to the endoplasmic reticulum membrane; and bacterial FtsY protein, which is believed to play a similar role to that played by the eukaryotic docking protein.
Methanogenic archaea produce methane via the anaerobic reduction of acetate or single carbon compounds [
]. Coenzyme M (CoM; 2-mercaptoethanesulphonic acid) serves as the terminal methyl carrier for this process. Previously thought to be unique to methanogenic archaea, CoM has also been found in methylotrophic bacteria.
Biosynthesis of CoM begins with the Michael addition of sulphite to phosphoenolpyruvate, forming 2-phospho-3-sulpholactate (PSL). This reaction is catalyzed by members of this family, PSL synthase (ComA) [
]. Subsequently, PSL is dephosphorylated by phosphosulpholactate phosphatase (ComB) to form 3-sulpholactate [], which is then converted to 3-sulphopyruvate by L-sulpholactate dehydrogenase (ComC;
) [
]. Sulphopyruvate decarboxylase (ComDE; ) converts 3-sulphopyruvate to sulphoacetaldehyde [
]. Reductive thiolation of sulphoacetaldehyde is the final step.This entry also includes some proteins from plants and fungi, such as HEAT-STRESS-ASSOCIATED 32 from Arabidopsis [
].
This is a group of eukaryotic proteins with no known function. Proteins in this entry include budding yeast Emi1, which is required for transcriptional induction of the early meiotic-specific transcription factor Ime1 [
]. Deletion of Emi1 affects mitochondrial morphology [].
Proteolipid membrane potential modulator is an evolutionarily conserved proteolipid in the plasma membrane which, in S. pombe, is transcriptionally regulated by the Spc1 stress MAPK (mitogen-activated protein kinases) pathway. It functions to modulate the membrane potential, particularly to resist high cellular cation concentration. In eukaryotic organisms, stress-activated mitogen-activated protein kinases play crucial roles in transmitting environmental signals that will regulate gene expression for allowing the cell to adapt to cellular stress. Pmp3-like proteins are highly conserved in bacteria, yeast, nematode and plants [
].Proteins in this entry include the PMP3 as well as several other proteins that have been shown [
] to be evolutionary related. Theseare small proteins of from 52 to 140 amino-acid resiudes that contain two transmembrane domains and belong to the UPF0057 (PMP3) protein family.
Initiation factor 3 (IF-3) (gene infC) is one of the three factors required for the
initiation of protein biosynthesis in bacteria. IF-3 is thought to function as a fidelity factor during the assembly of the ternary initiation complex which consist of
the 30S ribosomal subunit, the initiator tRNA and the messenger RNA. IF-3 is a basicprotein that binds to the 30S ribosomal subunit [
]. The chloroplast initiation factor IF-3(chl) is a protein that enhances the poly(A,U,G)-dependent binding of the initiator tRNA to chloroplast ribosomal
30s subunits in which the central section is evolutionary related to the sequence of bacterial IF-3 [
]. The signature pattern for this entry was made from a highly conserved region located in the central section of bacterial and plant chloroplast IF-3.
Proteins synthesized on the ribosome and processed in the endoplasmic reticulum are transported from the Golgi apparatus to the trans-Golgi network (TGN), and from there via small carrier vesicles to their final destination compartment. These vesicles have specific coat proteins (such as clathrin or coatomer) that are important for cargo selection and direction of transport [
]. Clathrin coats contain both clathrin (acts as a scaffold) and adaptor complexes that link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. The two major types of clathrin adaptor complexes are the heterotetrameric adaptor protein (AP) complexes, and the monomeric GGA (Golgi-localising, Gamma-adaptin ear domain homology, ARF-binding proteins) adaptors [,
].AP (adaptor protein) complexes are found in coated vesicles and clathrin-coated pits. AP complexes connect cargo proteins and lipids to clathrin at vesicle budding sites, as well as binding accessory proteins that regulate coat assembly and disassembly (such as AP180, epsins and auxilin). There are different AP complexes in mammals. AP1 is responsible for the transport of lysosomal hydrolases between the TGN and endosomes [
]. AP2 associates with the plasma membrane and is responsible for endocytosis []. AP3 is responsible for protein trafficking to lysosomes and other related organelles []. AP4 is less well characterised. AP complexes are heterotetramers composed of two large subunits (adaptins), a medium subunit (mu) and a small subunit (sigma). For example, in AP1 these subunits are gamma-1-adaptin, beta-1-adaptin, mu-1 and sigma-1, while in AP2 they are alpha-adaptin, beta-2-adaptin, mu-2 and sigma-2. Each subunit has a specific function. Adaptins recognise and bind to clathrin through their hinge region (clathrin box), and recruit accessory proteins that modulate AP function through their C-terminal ear (appendage) domains. Mu recognises tyrosine-based sorting signals within the cytoplasmic domains of transmembrane cargo proteins []. One function of clathrin and AP2 complex-mediated endocytosis is to regulate the number of GABA(A) receptors available at the cell surface []. AP adaptor alpha-adaptin can be divided into a trunk domain and the C-terminal appendage domain (or ear domain), separated by a linker region. The C-terminal appendage domain regulates translocation of endocytic accessory proteins to the bud site [
].This entry represents a subdomain of the appendage (ear) domain of alpha-adaptin from AP clathrin adaptor complexes. This domain has a three-layer arrangement, α-β-alpha, with a bifurcated antiparallel β-sheet [
].
Adaptor protein complex AP-2 has a role in clathrin-mediated endocytosis and intracellular transport [
]. AP-2 links clathrin to membrane lipids and transmembrane cargoes at the vesicle budding site []. It consists of two large subunits termed adaptins (alpha and beta subunits), a medium-sized one (mu), and a small one (sigma). It is thought to act in cargo selection by interaction with selection motifs encoded in the cytoplasmic tails of cargo molecules. The N-terminal domains of the adaptins, together with the mu and sigma subunits, constitute the 'head' of the adaptor, which interacts with plasma membrane lipids and cargoes. AP-2 plays a role in the recycling of synaptic vesicle membranes from the presynaptic surface [].This family represents the alpha subunit of adaptor protein complex AP-2.
The serum amyloid A (SAA) proteins comprise a family of vertebrate amphipathic α-helical apolipoproteins that associate predominantly with high density lipoproteins (HDL) [
,
]. They play a role in the mobilisation of cholesterol for tissue repair and regeneration []. The synthesis of these proteins is greatly increased (as much as a 1000 fold) in inflammation, being a major acute phase reactant together with C-reactive protein. They act as cytokine-like proteins that are involved in cell-cell communication and in inflammatory, immunologic, neoplastic and protective pathways []. Prolonged elevation of plasma SAA levels, as in chronic inflammation, results in a pathological condition, called amyloidosis, which affects the liver, kidney and spleen and which is characterised by the highly insoluble accumulation of SAA in these tissues. During chronic inflammation, SAA association with HDL can change its protein and lipid composition which abrogates the HDL anti-atherogenic properties, contributing to a pro-atherogenic state [,
].
The CDC48 N-terminal domain is a protein domain found in AAA ATPases including cell division protein 48 (CDC48), VCP-like ATPase (VAT) and N-ethylmaleimide sensitive fusion protein. It is a substrate recognition domain which binds polypeptides, prevents protein aggregation, and catalyses refolding of permissive substrates. It is composed of two equally sized subdomains. The amino-terminal subdomain forms a double-psi β-barrel whose pseudo-twofold symmetry is mirrored by an internal sequence repeat of 42 residues. The carboxy-terminal subdomain forms a novel six-stranded β-clamp fold []. Together these subdomains form a kidney-shaped structure. This entry represents the amino-terminal subdomain.
This family includes yeast CDC48 (cell division control protein 48) and the human orthologue, transitional endoplasmic reticulum ATPase (valosin-containing protein) [
]. It also includes CDC48 homologues from Archaea []. These proteins in eukaryotes are involved in the budding and transfer of membrane from the transitional endoplasmic reticulum to the Golgi apparatus. The archeal homologue of eukaryotic CDC48/p97 functions with the 20S proteasome by unfolding substrates and passing them on for degradation []. CDC48 consists of an N-terminal domain that binds two hexameric ATPase rings (D1 and D2) surrounding a central pore [].
This entry represents a group of LSM domain containing proteins functioning in RNA processing, including U6 snRNA-associated Sm-like protein LSm4 and small nuclear ribonucleoproteins Sm D1 and D3.LSm4 is a component of LSm protein complexes, which are involved in RNA processing and may function in a chaperone-like manner. It binds specifically to the 3'-terminal U-tract of U6 snRNA [
,
]. SmD1 is involved in pre-mRNA splicing. It binds snRNA U1, U2, U4 and U5, which contain a highly conserved structural motif called the Sm binding site. It also binds telomerase RNA and is required for its accumulation [
,
].SmD3 is a core protein of small nuclear ribonucleoprotein (snRNP) essential for splicing of primary transcripts [
]. It appears to function in the U7 snRNP complex that is involved in histone 3'-end processing. It binds to the downstream cleavage product (DCP) of histone pre-mRNA in a U7 snRNP dependent manner [].
The MutS family of proteins is named after the Salmonella typhimurium MutS protein involved in mismatch repair. Homologues of MutS have been found in many species including eukaryotes (MSH 1, 2, 3, 4, 5, and 6 proteins), archaea and bacteria, and together these proteins have been grouped into the MutS family. Although many of these proteins have similar activities to the E. coli MutS, there is significant diversity of function among the MutS family members. Inter-species homologues may have arisen through frequent ancient horizontal gene transfer of MutS (and MutL) from bacteria to archaea and eukaryotes via endosymbiotic ancestors of mitochondria and chloroplasts [
]. This entry represents endonuclease MutS2. MutS2 is a paralogue of MutS and is not involved in DNA mismatch repair but in the suppression of homologous recombination [
,
,
,
]. It may therefore have a key role in the control of bacterial genetic diversity.
Glucose-6-phosphate dehydrogenase (
) (G6PDH) is a ubiquitous protein, present in bacteria and all eukaryotic cell types [
]. The enzyme catalyses the the first step in the pentose pathway, i.e. the conversion of glucose-6-phosphate to gluconolactone 6-phosphate in the presence of NADP, producing NADPH. The ubiquitous expression of the enzyme gives it a major role in the production of NADPH for the many NADPH-mediated reductive processes in all cells, and is critical for NADPH homeostasis and redox regulation []. Deficiency of G6PDH is a common genetic abnormality affecting millions of people worldwide. Many sequence variants, most caused by single point mutations, are known, exhibiting a wide variety of phenotypes with the distinctive one being chronic and drug- or food-induced hemolytic anemia, attributed to the inability to produce NADPH and withstand harmful oxidants in erythrocyte cells [,
].This entry represents the NAD-binding domain of glucose-6-phosphate dehydrogenase.
Glucose-6-phosphate dehydrogenase (
) (G6PDH) is a ubiquitous protein, present in bacteria and all eukaryotic cell types [
]. The enzyme catalyses the the first step in the pentose pathway, i.e. the conversion of glucose-6-phosphate to gluconolactone 6-phosphate in the presence of NADP, producing NADPH. The ubiquitous expression of the enzyme gives it a major role in the production of NADPH for the many NADPH-mediated reductive processes in all cells, and is critical for NADPH homeostasis and redox regulation []. Deficiency of G6PDH is a common genetic abnormality affecting millions of people worldwide. Many sequence variants, most caused by single point mutations, are known, exhibiting a wide variety of phenotypes with the distinctive one being chronic and drug- or food-induced hemolytic anemia, attributed to the inability to produce NADPH and withstand harmful oxidants in erythrocyte cells [,
].
Glucose-6-phosphate dehydrogenase (G6PD) [
] catalyses the first step in the pentose pathway, the reduction of glucose-6-phosphate to gluconolactone 6-phosphate. A lysine residue has been identified as a reactive nucleophile associated with the activity of the enzyme []. The sequence around this lysine is totally conserved from bacterial to mammalian G6PD's and is used as the pattern to identify the proteins associated with this entry.
Glucose-6-phosphate dehydrogenase (
) (G6PDH) is a ubiquitous protein, present in bacteria and all eukaryotic cell types [
]. The enzyme catalyses the the first step in the pentose pathway, i.e. the conversion of glucose-6-phosphate to gluconolactone 6-phosphate in the presence of NADP, producing NADPH. The ubiquitous expression of the enzyme gives it a major role in the production of NADPH for the many NADPH-mediated reductive processes in all cells, and is critical for NADPH homeostasis and redox regulation []. Deficiency of G6PDH is a common genetic abnormality affecting millions of people worldwide. Many sequence variants, most caused by single point mutations, are known, exhibiting a wide variety of phenotypes with the distinctive one being chronic and drug- or food-induced hemolytic anemia, attributed to the inability to produce NADPH and withstand harmful oxidants in erythrocyte cells [,
].This entry represents the C-terminal domain of glucose-6-phosphate dehydrogenase.
Eukaryotic translation initiation factor 3 subunit H
Type:
Family
Description:
Eukaryotic translation initiation factor 3 subunit H (eIF3h) 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 [
,
]. It is a non-peptidase homologue in peptidase family M67 (MEROPS identifier M67.971).Results suggest that eIF3h regulates cell growth and viability, and that over-expression of the gene may provide growth advantage to prostate, breast, and liver cancer cells [
,
,
].
Aminoacyl-tRNA synthetase, class I, anticodon-binding 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 [].Structurally, an α-helix-bundle anticodon-binding domain characterises the class Ia synthetases, whereas the class Ib synthetases, GlnRS and GluRS have distinct anticodon-binding domains. The anticodon-binding domain has a multi-helical structure, consisting of two all-alpha subdomains. The Rossmann-fold, made up of alternate α-helices and β-sheets involved in ATP binding in the extended conformation, and the anticodon-binding domains are connected by a beta-α-α-beta-alpha topology ('SC fold') domain that contains the class I specific KMSKS motif [
,
].
