Budding yeast Ist1 is involved in a late step in sorting of cargo proteins of the multivesicular body (MVB) for incorporation into intralumenal vesicles [
]. This entry also includes Ist1 homologues from animals and plants. Human Ist1 functions in the ESCRT (endosomal sorting complexes required for transport) pathway and is required for efficient abscission during HeLa cell cytokinesis []. Human Ist1 binds the transport (MIT) domain of VPS4, LIP5, and Spartin via its C-terminal MIT-interacting motif (MIM) [].
Cytochromes b5 are ubiquitous electron transport proteins found in animals, plants and
yeasts []. The microsomal and mitochondrial variants are membrane-bound, while those from erythrocytes and other animal tissues are water-soluble [
,
]. The 3D structure of bovine cyt b5 is known, the
fold belonging to the alpha+beta class, with 5 strands and 5 short helicesforming a framework for supporting a central haem group [
]. The cytochrome b5 domain is similar to that of a numberof oxidoreductases, such as plant and fungal nitrate reductases, sulphite oxidase, yeast
flavocytochrome b2 (L-lactate dehydrogenase) and plant cyt b5/acyl lipid desaturasefusion protein.
This conserved site includes the first of the two histidine heme ligands, which are found in the heme-binding domain of cytochrome b5 family.
Adenylosuccinate synthetase (
) plays an important role in purine biosynthesis, by catalysing the GTP-dependent conversion of IMP and aspartic acid to AMP. Adenylosuccinate synthetase has been characterised from various sources ranging from Escherichia coli (gene purA) to vertebrate tissues. In vertebrates, two isozymes are present: one involved in purine biosynthesis and the other in the purine nucleotide cycle.
The crystal structure of adenylosuccinate synthetase from E. coli reveals that the dominant structural element of each monomer of the homodimer is a central β-sheet of 10 strands. The first nine strands of the sheet are mutually parallel with right-handed crossover connections between the strands. The 10th strand is antiparallel with respect to the first nine strands. In addition, the enzyme has two antiparallel β-sheets, comprised of two strands and three strands each, 11 α-helices and two short 3/10-helices. Further, it has been suggested that the similarities in the GTP-binding domains of the synthetase and the p21ras protein are an example of convergent evolution of two distinct families of GTP-binding proteins [
]. Structures of adenylosuccinate synthetase from Triticum aestivum and Arabidopsis thaliana when compared with the known structures from E. coli reveals that the overall fold is very similar to that of the E. coli protein [].This entry represents the conserved octapeptide located in the N-terminal section that is involved in GTP-binding [
].
Adenylosuccinate synthetase (
) plays an important role in purine biosynthesis, by catalysing the GTP-dependent conversion of IMP and aspartic acid to AMP. IMP and L-aspartate are conjugated in a two-step reaction accompanied by the hydrolysis of GTP to GDP in the presence of Mg2+. In the first step, the r-phosphate group of GTP is transferred to the 6-oxygen atom of IMP. An aspartate then displaces this 6-phosphate group to form the product adenylosuccinate. Adenylosuccinate synthetase has been characterised from various sources ranging from Escherichia coli (gene purA) to vertebrate tissues. In vertebrates, two isozymes are present: one involved in purine biosynthesis and the other in the purine nucleotide cycle.
The crystal structure of adenylosuccinate synthetase from E. coli reveals that the dominant structural element of each monomer of the homodimer is a central β-sheet of 10 strands. The first nine strands of the sheet are mutually parallel with right-handed crossover connections between the strands. The 10th strand is antiparallel with respect to the first nine strands. In addition, the enzyme has two antiparallel β-sheets, comprised of two strands and three strands each, 11 α-helices and two short 3/10-helices. Further, it has been suggested that the similarities in the GTP-binding domains of the synthetase and the p21ras protein are an example of convergent evolution of two distinct families of GTP-binding proteins [
]. Structures of adenylosuccinate synthetase from Triticum aestivum and Arabidopsis thaliana when compared with the known structures from E. coli reveals that the overall fold is very similar to that of the E. coli protein [].
Monoamine oxidases (MAO) A and B are encoded by two genes derived from a common ancestral gene [
]. The enzymes catalyse the oxidative deamination of biogenic and xenobiotic amines and have important roles in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues []. MAO-A preferentially oxidises biogenic amines such as 5-hydroxytryptamine, norepinephrine and epinephrine. MAO-A deficiency has been linked to Brunner's syndrome, a form of X-linked nondysmorphic mild mental retardation [].The protein contains two similarly-sized subunits, one of which contains covalently-bound flavin adenine dinucleotide (FAD). The FAD binding site lies near the C terminus; at the N terminus are features characteristic of the ADP-binding fold, suggesting that this region is also involved in FAD binding [
]. The A and B forms of the enzyme share 70% sequence identity; both contain the pentapeptide Ser-Gly-Gly-Cys-Tyr, the cysteine of which binds FAD [].
This entry consists of various amine oxidases, including maize polyamine oxidase (PAO) [
], L-amino acid oxidases (LAO) and various flavin containing monoamine oxidases (MAO). The aligned region includes the flavin binding site of these enzymes. In vertebrates, MAO plays an important role in regulating the intracellular levels of amines via their oxidation; these include various neurotransmitters, neurotoxins and trace amines []. In lower eukaryotes such as aspergillus and in bacteria the main role of amine oxidases is to provide a source of ammonium []. PAOs in plants, bacteria and protozoa oxidise spermidine and spermine to an aminobutyral, diaminopropane and hydrogen peroxide and are involved in the catabolism of polyamines []. Other members of this family include tryptophan 2-monooxygenase, putrescine oxidase, corticosteroid binding proteins and antibacterial glycoproteins.
A sequence of about thirty to forty amino-acid residues long found in the sequence of epidermal growth factor (EGF)
has been shown [,
,
,
] to be present, in a moreor less conserved form, in a large number of other, mostly animal proteins. The list of proteins currently known to
contain one or more copies of an EGF-like pattern is large and varied. The functional significance of EGF domains inwhat appear to be unrelated proteins is not yet clear. However, a common feature is that these repeats are found in
the extracellular domain of membrane-bound proteins or in proteins known to be secreted (exception: prostaglandinG/H synthase). The EGF domain includes six cysteine residues which have been shown (in EGF) to be involved in disulphide
bonds. The main structure is a two-stranded β-sheet followed by a loop to a C-terminal short two-stranded sheet.Subdomains between the conserved cysteines vary in length.
This entry represents a conserved site in the EGF-like domain.
This entry represents a domain found twice in the protein DUF642 L-galactono-1,4-lactone-responsive gene 2 from Arabidopsis thaliana (DGR2) and similar proteins found in plants and bacteria. DGR2 is involved in the regulation of testa rupture during seed germination [
] and in the development of roots and rosettes []. This domain was previously known as DUF642.
Lipoxygenases ([intenz:1.13.11.-]) are a class of iron-containing dioxygenases which catalyses the hydroperoxidation of lipids, containing a cis,cis-1,4-pentadiene structure. They are common in plants where they may be involved in a number of diverse aspects of plant physiology including growth and development, pest resistance, and senescence or responses to wounding. Lipoxygenases can be classified as 9- and 13-lipoxygenases, according to the position of oxygen incorporation in linoleic acid and linolenic acid, the most important substrates for LOX catalysis in plants. There are six A. thaliana lipoxygenases identified: AtLOX1-6, among which AtLOX-1 and AtLOX-5 are 9S-lipoxygenases, and AtLOX-2, AtLOX-3, AtLOX-4 and AtLOX-6 are 13S-lipoxygenases [
].
This superfamily represents a domain found in lipoxygenases.Lipoxygenases ([intenz:1.13.11.-]) are a class of iron-containing dioxygenases which catalyses the hydroperoxidation of lipids, containing a cis,cis-1,4-pentadiene structure. They are common in plants where they may be involved in a number of diverse aspects of plant physiology including growth and development, pest resistance, and senescence or responses to wounding. Plants express a variety of cytosolic isozymes as well as what seems to be a chloroplast isozyme [].The iron atom in lipoxygenases is bound by four ligands, three of which are
histidine residues []. Six histidines are conserved in all lipoxygenase sequences, five of them are found clustered in a stretch of 40 amino acids. This region contains two of the three iron-ligands; the other histidines have been shown [] to be important for the activity of lipoxygenases.
Lipoxygenases ([intenz:1.13.11.-]) are a class of iron-containing dioxygenases which catalyses the hydroperoxidation of lipids, containing a cis,cis-1,4-pentadiene structure. They are common in plants where they may be involved in a number of diverse aspects of plant physiology including growth and development, pest resistance, and senescence or responses to wounding. In mammals a number of lipoxygenases isozymes are involved in the metabolism of prostaglandins and leukotrienes []. Sequence data is available for the following lipoxygenases: Plant lipoxygenases (
). Plants express a variety of cytosolic isozymes as well as what seems to be a chloroplast isozyme [
].Mammalian arachidonate 5-lipoxygenase ().
Mammalian arachidonate 12-lipoxygenase (
).
Mammalian arachidonate 15-lipoxygenase B (also known as erythroid cell-specific 15-lipoxygenase;
).
The iron atom in lipoxygenases is bound by four ligands, three of which are
histidine residues []. Six histidines are conserved in all lipoxygenase sequences, five of them are found clustered in a stretch of 40 amino acids. This region contains two of the three iron-ligands; the other histidines have been shown [] to be important for the activity of lipoxygenases.This entry represents the C-terminal region of these proteins.
Lipoxygenases ([intenz:1.13.11.-]) are a class of iron-containing dioxygenases which catalyses the hydroperoxidation of lipids, containing a cis,cis-1,4-pentadiene structure. They are common in plants where they may be involved in a number of diverse aspects of plant physiology including growth and development, pest resistance, and senescence or responses to wounding. In mammals a number of lipoxygenases isozymes are involved in the metabolism of prostaglandins and leukotrienes []. Sequence data is available for the following lipoxygenases: Plant lipoxygenases (
). Plants express a variety of cytosolic isozymes as well as what seems to be a chloroplast isozyme [].Mammalian arachidonate 5-lipoxygenase (
).
Mammalian arachidonate 12-lipoxygenase (
).
Mammalian arachidonate 15-lipoxygenase B (also known as erythroid cell-specific 15-lipoxygenase;
).
The iron atom in lipoxygenases is bound by four ligands, three of which are
histidine residues []. Six histidines are conserved in all lipoxygenase sequences, five of them are found clustered in a stretch of 40 amino acids. This region contains two of the three iron-ligands; the other histidines have been shown [] to be important for the activity of lipoxygenases.This entry represents a motif that contains the iron-binding sites.
Lipoxygenases ([intenz:1.13.11.-]) are a class of iron-containing dioxygenases which catalyses the hydroperoxidation of lipids, containing a cis,cis-1,4-pentadiene structure. They are common in plants where they may be involved in a number of diverse aspects of plant physiology including growth and development, pest resistance, and senescence or responses to wounding. In mammals a number of lipoxygenases isozymes are involved in the metabolism of prostaglandins and leukotrienes [
]. Sequence data is available for the following lipoxygenases: Plant lipoxygenases (
). Plants express a variety of cytosolic isozymes as well as what seems to be a chloroplast isozyme [
].Mammalian arachidonate 5-lipoxygenase (
).
Mammalian arachidonate 12-lipoxygenase (
).
Mammalian arachidonate 15-lipoxygenase B (also known as erythroid cell-specific 15-lipoxygenase;
).
The iron atom in lipoxygenases is bound by four ligands, three of which are
histidine residues []. Six histidines are conserved in all lipoxygenase sequences, five of them are found clustered in a stretch of 40 amino acids. This region contains two of the three iron-ligands; the other histidines have been shown [] to be important for the activity of lipoxygenases.This entry represents a motif that contains two of the conserved histidines.
This entry represents a domain found in a variety of membrane or lipid associated proteins. It is known as the PLAT (Polycystin-1, Lipoxygenase, Alpha-Toxin) domain or LH2 (Lipoxygenase homology) domain, is found in a variety of membrane or lipid associated proteins. Structurally, this domain forms a β-sandwich composed of two sheets of four strands each [
,
,
]. The most highly conserved regions coincide with the β-strands, with most of the highly conserved residues being buried within the protein. An exception to this is a surface lysine or arginine that occurs on the surface of the fifth β-strand of the eukaryotic domains. In pancreatic lipase, the lysine in this position forms a salt bridge with the procolipase protein. The conservation of a charged surface residue may indicate the location of a conserved ligand-binding site. It is thought that this domain may mediate membrane attachment via other protein binding partners.
Lipoxygenases ([intenz:1.13.11.-]) are a class of iron-containing dioxygenases which catalyses the hydroperoxidation of lipids, containing a cis,cis-1,4-pentadiene structure. They are common in plants where they may be involved in a number of diverse aspects of plant physiology including growth and development, pest resistance, and senescence or responses to wounding. In mammals a number of lipoxygenases isozymes are involved in the metabolism of prostaglandins and leukotrienes []. Sequence data is available for the following lipoxygenases: Plant lipoxygenases (
). Plants express a variety of cytosolic isozymes as well as what seems to be a chloroplast isozyme [
].Mammalian arachidonate 5-lipoxygenase (
).
Mammalian arachidonate 12-lipoxygenase (
).
Mammalian arachidonate 15-lipoxygenase B (also known as erythroid cell-specific 15-lipoxygenase;
).
The iron atom in lipoxygenases is bound by four ligands, three of which are
histidine residues []. Six histidines are conserved in all lipoxygenase sequences, five of them are found clustered in a stretch of 40 amino acids. This region contains two of the three iron-ligands; the other histidines have been shown [] to be important for the activity of lipoxygenases.
Urease (urea amidohydrolase,
) is a nickel-dependent metalloenzyme that catalyses the hydrolysis of urea to form ammonia and carbon dioxide. Nickel-dependent ureases are found in bacteria, archaea, fungi and plants. Their primary role is to allow the use of external and internally-generated urea as a nitrogen source. The enzyme consists of three subunits, alpha, beta and gamma, which can exist as separate proteins or can be fused on a single protein chain. The α-β-γ heterotrimer forms multimers, mainly trimers. The subunit composition of urease from different sources varies [
], but each holoenzyme consists of four domains []: three structural domains and a nickel-binding catalytic domain common to amidohydrolases []. In Klebsiella aerogenes, urease exists as an alpha, beta and gamma subunit, with the alpha subunit possessing the catalytic domain. In Helicobacter pylori, the gamma and beta subunits are fused and called the alpha subunit, while the catalytic subunit is called the beta subunit. In Canavalia ensiformis, urease has a fused gamma-beta-alpha organisation.This entry represents the urease gamma subunit. It also identifies gamma subunits fused with other urease subunits, as found in Helicobacter and other species.
Urease is a nickel-dependent metalloenzyme that catalyses the hydrolysis of urea to form ammonia and carbon dioxide. Nickel-dependent ureases are found in bacteria, archaea, fungi and plants. Their primary role is to allow the use of external and internally-generated urea as a nitrogen source. The enzyme consists of three subunits, alpha, beta and gamma, which can exist as separate proteins or can be fused on a single protein chain. The α-β-γ heterotrimer forms multimers, mainly trimers. The large alpha subunit is the catalytic domain containing an active site with a bi-nickel centre complexed by a carbamylated lysine. The beta and gamma subunits play a role in subunit association to form the higher order trimers [
,
,
,
,
].This entry represents the urease beta subunit and similar sequences mainly found in bacteria and fungi. In Helicobacter pylori, the gamma and beta subunits are fused and known (confusingly) as the alpha subunit.
Proteins containing this domain are enzymes from a large metal dependent hydrolase superfamily [
]. The family includes adenine deaminase () that hydrolyses adenine to form hypoxanthine and ammonia. This reaction is important for adenine utilisation as a purine and also as a nitrogen source [
]. The family also includes dihydroorotase and N-acetylglucosamine-6-phosphate deacetylases (). The domain is also found in the urease alpha subunit, where it is the catalytic domain [
].
Urease (urea amidohydrolase,
) is a nickel-binding enzyme that catalyses the hydrolysis of urea to form ammonia and carbamate [
]. It is mainly found in plant seeds, microorganisms and invertebrates. In plants, urease is a hexamer of identical chains, but the subunit composition of urease from different sources varies [], in bacteria [] it consists of either two or three different subunits (alpha, beta and gamma).Urease binds two nickel ions per subunit; four histidine, an aspartate and a carbamated-lysine serve as ligands to these metals; an additional histidine is involved in the catalytic mechanism [
]. The urease domain forms an (alpha beta)(8) barrel structure with structural similarity to other metal-dependent hydrolases, such as adenosine and AMP deaminase and phosphotriesterase. Urease is unique among nickel metalloenzymes in that it catalyses a hydrolysis rather than a redox reaction.The orthologous protein is known as the alpha subunit (ureC) in most other bacteria.In Helicobacter pylori, the gamma and beta domains are fused and called the alpha subunit (
). The catalytic subunit (called beta or B) has the same organisation as the Klebsiella alpha subunit. Jack bean (Canavalia ensiformis) urease has a fused gamma-beta-alpha organisation (
). This entry describes the urease alpha subunit UreC (designated beta or B chain, UreB in Helicobacter species).
Urease (urea amidohydrolase,
) is a nickel-binding enzyme
that catalyses the hydrolysis of urea to carbon dioxide and ammonia []. Historically, it was the first enzyme to be crystallized (in 1926). It is mainly found in plant seeds,
microorganisms and invertebrates. In plants, urease is a hexamer of identicalchains. In bacteria [
], it consists of either two or three different subunits(alpha, beta and gamma).
Urease binds two nickel ions per subunit; four histidine, an aspartate and acarbamated-lysine serve as ligands to these metals; an additional histidine is
involved in the catalytic mechanism []. The urease domain forms an (alphabeta)(8) barrel structure with structural similarity to other metal-dependent hydrolases, such
as adenosine and AMP deaminase and phosphotriesterase.This entry represents a conserved region that contains the active site histidine.
Urease (urea amidohydrolase,
) catalyses the hydrolysis of urea to form ammonia and carbamate. The subunit composition of urease from different sources varies [
], but each holoenzyme consists of four structural domains []: three structural domains and a nickel-binding catalytic domain common to amidohydrolases []. Urease is unique among nickel metalloenzymes in that it catalyses a hydrolysis rather than a redox reaction. In Helicobacter pylori, the gamma and beta domains are fused and called the alpha subunit (). The catalytic subunit (called beta or B) has the same organisation as the Klebsiella alpha subunit. Jack bean (Canavalia ensiformis) urease has a fused gamma-beta-alpha organisation (
).
The N-terminal domain is a composite domain and plays a major trimer stabilising role by contacting the catalytic domain of the symmetry related alpha-subunit [
].
The composite domain of metal-dependent hydrolases has a pseudo-barrel fold that is interrupted by the catalytic beta/alpha barrel domain. This domain is found in a variety of bacterial and fungal enzymes, including: cytosine deaminase, an enzyme that is important in the pyrimidine salvage pathway [
]; the alpha-subunit of urease, a virulence factor of gastric pathogens such as Helicobacter pylori (Campylobacter pylori) []; D- and L-hydantoinases (dihydropyrimidinase), which catalyse the production of D- and L-amino acids, respectively []; isoaspartyl dipeptidase from Escherichia coli, which functions in protein degradation []; N-acetylglucosamine-6-phosphate deacetylase, which is an enzyme from the biosynthetic pathway to amino-sugar-nucleotides []; and N-acyl-D-amino acid amidohydrolase (D-aminoacylase), involved in the synthesis of D-amino acids [].
Urease (urea amidohydrolase,
) a nickel-binding enzyme that catalyses the hydrolysis of urea to form ammonia and carbamate [
]. It is mainly found in plant seeds, microorganisms and invertebrates. In plants, urease is a hexamer of identical chains, but the subunit composition of urease from different sources varies []; in bacteria [] it consists of either two or three different subunits (alpha, beta and gamma).Urease binds two nickel ions per subunit; four histidine, an aspartate and a carbamated-lysine serve as ligands to these metals; an additional histidine is involved in the catalytic mechanism [
]. The urease domain forms an (alpha beta)(8) barrel structure with structural similarity to other metal-dependent hydrolases, such as adenosine and AMP deaminase (see ) and phosphotriesterase see
). Urease is unique among nickel metalloenzymes in that it catalyses a hydrolysis rather than a redox reaction.
In Helicobacter pylori, the gamma and beta domains are fused and called the alpha subunit (
). The catalytic subunit (called beta or B) has the same organisation as the Klebsiella alpha subunit. Jack bean (Canavalia ensiformis) urease has a fused gamma-beta-alpha organisation (
).
This entry describes the C-terminal domain of urease alpha subunit UreC (designated beta or UreB in Helicobacter species).Urease (
) belongs to MEROPS peptidase family M38 (clan MJ).
This entry represents the subunit D (NuoD) of NADH-quinone oxidoreductase (
) and the subunit H (NdhH) of NAD(P)H-quinone oxidoreductase ([intenz:1.6.5.-]). NADH-quinone (Q) oxidoreductase is a large and complex redox proton pump, which utilises the free energy derived from oxidation of NADH with lipophilic electron/proton carrier Q to translocate protons across the membrane to generate an electrochemical proton gradient []. Subunit D (NuoD) is a 49kDa polypeptide that appears to be evolutionarily important in determining the physiological function of complex I/NDH-1 [].
This is the helicase associated domain (HA2) found as a diverse set of RNA helicases. It has an all α-helical fold that can be divided in two subdomains, an N-terminal degenerated winged helix (WH) and a C-terminal ratchet-like domain [
,
,
,
]. This domain collaborates with the RecA domains at the N-terminal in the formation of a RNA binding channel to allow the helicases to keep a stable grip on the RNA.
Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [
,
,
,
,
]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few []. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target. This entry represents the AN1-type zinc finger domain, which has a dimetal (zinc)-bound alpha/beta fold. This domain was first identified as a zinc finger at the C terminus of AN1
, a ubiquitin-like
protein in Xenopus laevis []. The AN1-type zinc finger contains six conserved cysteines and two histidines that could potentially coordinate 2 zinc atoms.Certain stress-associated proteins (SAP) contain AN1 domain, often in combination with A20 zinc finger domains (SAP8) or C2H2 domains (SAP16) [
]. For example, the human protein Znf216 has an A20 zinc-finger at the N terminus and an AN1 zinc-finger at the C terminus, acting to negatively regulate the NFkappaB activation pathway and to interact with components of the immune response like RIP, IKKgamma and TRAF6. The interact of Znf216 with IKK-gamma and RIP is mediated by the A20 zinc-finger domain, while its interaction with TRAF6 is mediated by the AN1 zinc-finger domain; therefore, both zinc-finger domains are involved in regulating the immune response []. The AN1 zinc finger domain is also found in proteins containing a ubiquitin-like domain, which are involved in the ubiquitination pathway [
]. Proteins containing an AN1-type zinc finger include:Ascidian posterior end mark 6 (pem-6) protein [
].Human AWP1 protein (associated with PRK1), which is expressed during early embryogenesis [
].Human immunoglobulin mu binding protein 2 (SMUBP-2), mutations in which cause muscular atrophy with respiratory distress type 1 [
].
Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [
,
,
,
,
]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few []. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target. This entry represents the zinc finger domain found in A20. A20 is an inhibitor of cell death that inhibits NF-kappaB activation via the tumour necrosis factor receptor associated factor pathway [
]. The zinc finger domains appear to mediate self-association in A20. These fingers also mediate IL-1-induced NF-kappa B activation.
This entry represents the UMP-CMP kinase subfamily of the adenylate kinase family. UMP-CMP kinase catalyses the phosphorylation of pyrimidine nucleoside monophosphates at the expense of ATP and is involved in de novo pyrimidine nucleotide biosynthesis [
,
]. In budding yeast, it is also known as Ura6 [].
The immunoglobulin (Ig) like fold, which consists of a β-sandwich of seven or more strands in two sheets with a greek-key topology, is one of the most common protein modules found in animals. Many different unrelated proteins share an Ig-like fold, which is often involved in interactions, commonly with other Ig-like domains via their β-sheets [
]. Of these, the "early"set (E set) domains are possibly related to the immunoglobulin (
) and/or fibronectin type III (
) Ig-like protein superfamilies. Ig-like E set domains include:
C-terminal domain of certain transcription factors, such as the pro-inflammatory transcription factor NF-kappaB, and the T-cell transcription factors NFAT1 and NFAT5 [
].Ig-like domains of sugar-utilising enzymes, such as galactose oxidase (C-terminal domain), sialidase (linker domain), and maltogenic amylase (N-terminal domain).C-terminal domain of arthropod haemocyanin, where many loops are inserted into the fold. These proteins act as dioxygen-transporting proteins.C-terminal domain of class II viral fusion proteins. These envelope glycoproteins are responsible for membrane fusion with target cells during viral invasion.Cytomegaloviral US (unique short) proteins. These type I membrane proteins help suppress the host immune response by modulating surface expression of MHC class I molecules [
].Molybdenium-containing oxidoreductase-like dimerisation domain found in enzymes such as sulphite reductase.ML domains found in cholesterol-binding epididymal secretory protein E1, and in a major house-dust mite allergen; ML domains are implicated in lipid recognition, particularly the recognition of pathogen-related products.Rho-GDI-like signalling proteins, which regulate the activity of small G proteins [
].Cytoplasmic domain of inward rectifier potassium channels such as Girk1 and Kirbac1.1. These channels act as regulators of excitability in eukaryotic cells.N-terminal domain of transglutaminases, including coagulation factor XIII; many loops are inserted into the fold in these proteins. These proteins act to catalyse the cross-linking of various protein substrates [
].Filamin repeat rod domain found in proteins such as the F-actin cross-linking gelation factor ABP-120. These proteins interact with a variety of cellular proteins, acting as signalling scaffolds [
].Arrestin family of proteins, which contain a tandem repeat of two elaborated Ig-like domains contacting each other head-to-head. These proteins are key to the redirection of GPCR signals to alternative pathways [
].C-terminal domain of arginine-specific cysteine proteases, such as Gingipain-R, which act as major virulence factors of Porphyromonas gingivalis (Bacteroides gingivalis).Copper-resistance proteins, such as CopC, which act as copper-trafficking proteins [
].Cellulosomal scaffoldin proteins, such as CipC module x2.1. These proteins act as scaffolding proteins of cellulosomes, which contain cellulose-degrading enzymes [
].Quinohaemoprotein amine dehydrogenases (A chain), which contain a tandem repeat of two Ig-like domains. These proteins function in electron transfer reactions.Internalin Ig-like domains, which are truncated and fused to a leucine-rich repeat domain. These proteins are required for host cell invasion of Listeria species.
This domain is found in bacterial, mitochondrial and chloroplastic peptide chain release factors. In bacteria, termination of protein synthesis depends on the type I release factors, RF1 and RF2 [
]. Both contain this domain.
In contrast to other RNA-binding domains, the about 65 amino acids long dsRBD domain [
,
,
] has been found in a number of proteins that specifically recognise double-stranded RNAs. The dsRBD domain is also known as DSRM (Double-Stranded RNA-binding Motif). dsRBD proteins are mainly involved in posttranscriptional gene regulation, for example by preventing the expression of proteins or by mediating RNAs localization. This domain is also found in RNA editing proteins. Interaction of the dsRBD with RNA is unlikely to involve the recognition of specific sequences [,
,
]. Nevertheless, multiple dsRBDs may be able to act in combination to recognise the secondary structure of specific RNAs (i.e. Staufen) []. NMR analysis of the third dsRBD of Drosophila Staufen have revealed an α-β-β-β-α structure [].
Peptide chain release factors (RFs) are required for the termination of protein biosynthesis [
]. At present two classes of RFs can be distinguished. Class I RFs bind to ribosomes that have encountered a stop codon at their decoding site and induce release of the nascent polypeptide. Class II RFs are GTP-binding proteins that interact with class I RFs and enhance class I RF activity. In prokaryotes there are two class I RFs that act in a codon specific manner []: RF-1 (gene prfA) mediates UAA and UAG-dependent termination while RF-2 (gene prfB), which is represented by this entry, mediates UAA and UGA-dependent termination. RF-1 and RF-2 are structurally and evolutionary related proteins which have been shown [] to be part of a larger family.This entry represents peptide chain release factor 2 (PrfB, RF-2). It also includes chloroplastic release factor PrfB, which is required for the proper translation and stability of UGA-containing transcripts in chloroplasts [
].
Peptide chain release factors (RFs) are required for the termination of protein biosynthesis [
]. At present two classes of RFs can be distinguished. Class I RFs bind to ribosomes that have encountered a stop codon at their decoding site and induce release of the nascent polypeptide. Class II RFs are GTP-binding proteins that interact with class I RFs and enhance class I RFactivity. In prokaryotes there are two class I RFs that act in a codon specific manner [
]: RF-1(gene prfA) mediates UAA and UAG-dependent termination while RF-2 (gene prfB) mediates UAA and UGA-dependent termination. RF-1 and RF-2 are structurally and evolutionary related proteins which have been shown to be part of a larger family [].
This domain is named after Bet v 1, the major birch pollen allergen. Bet v 1 belongs to family 10 of plant pathogenesis-related proteins (PR-10), cytoplasmic proteins of 15-17 kd that are wide-spread among dicotyledonous plants [
]. In recent years, a number of diverse plant proteins with low sequence similarity to Bet v 1 was identified. A classification by sequence similarity yielded several subfamilies related to PR-10 []:Pathogenesis-related proteins PR-10: These proteins were identified as major tree pollen allergens in birch and related species (hazel, alder), as plant food allergens expressed in high levels in fruits, vegetables and seeds (apple, celery, hazelnut), and as pathogenesis-related proteins whose expression is induced by pathogen infection, wounding, or abiotic stress. Hyp-1 (
), an enzyme involved in the synthesis of the bioactive naphthodianthrone hypericin in St. John's wort (Hypericum perforatum) also belongs to this family. Most of these proteins were found in dicotyledonous plants. In addition, related sequences were identified in monocots and conifers.
Cytokinin-specific binding proteins: These legume proteins bind cytokinin plant hormones [].(S)-Norcoclaurine synthases are enzymes catalysing the condensation of dopamine and 4-hydroxyphenylacetaldehyde to (S)-norcoclaurine, the first committed step in the biosynthesis of benzylisoquinoline alkaloids such as morphine [
]. Major latex proteins and ripening-related proteins are proteins of unknown biological function that were first discovered in the latex of opium poppy (Papaver somniferum) and later found to be upregulated during ripening of fruits such as strawberry and cucumber [
]. The occurrence of Bet v 1-related proteins is confined to seed plants with the exception of a cytokinin-binding protein from the moss Physcomitrella patens (
).
This family consists of a number of plant proteins that are structurally related [
,
,
] and seem to be involved in pathogen defence response. These proteins include:Bet v I, the major pollen allergen from white birch. Bet v I is the main cause of type I allergic reactions observed in early spring.Aln g I, the major pollen allergen from alder.Api G I, the major allergen from celery.Car b I, the major pollen allergen from hornbeam.Cor a I, the major pollen allergen from hazel.Mal d I, the major pollen allergen from apple.Asparagus wound-induced protein AoPR1.Kidney bean pathogenesis-related proteins 1 and 2.Parsley pathogenesis-related proteins PR1-1 and PR1-3.Pea disease resistance response proteins pI49, pI176 and DRRG49-C.Pea abscisic acid-responsive proteins ABR17 and ABR18.Potato pathogenesis-related proteins STH-2 and STH-21.Soybean stress-induced protein SAM22.Major strawberry allergen proteins Fra a 1-2, 1-3 and 1.04 to 1.08
START (StAR-related lipid-transfer) is a lipid-binding domain in StAR, HD-ZIP and signalling proteins [
]. StAR (Steroidogenic Acute Regulatory protein) is a mitochondrial protein that is synthesised in response to luteinising hormone stimulation [].Expression of the protein in the absence of hormone stimulation is sufficient to induce
steroid production, suggesting that this protein is required in the acute regulation ofsteroidogenesis. Representatives of the START domain family have
been shown to bind different ligands such as sterols (StAR protein) andphosphatidylcholine (PC-TP). Ligand binding by the START domain can also
regulate the activities of other domains that co-occur with the START domainin multidomain proteins such as Rho-gap, the homeodomain,
and the thioesterase domain [,
]. The crystal structure of START domain of human MLN64 shows analpha/beta fold built around an U-shaped incomplete β-barrel. Most
importantly, the interior of the protein encompasses a 26 x 12 x 11 Angstromshydrophobic tunnel that is apparently large enough to bind a single
cholesterol molecule []. The START domain structure revealed an unexpectedsimilarity to that of the birch pollen allergen Bet v 1 and to bacterial
polyketide cyclases/aromatases [,
]. This superfamily represents an α/β sandwich structural domain found in a wide variety of protein families, including STAR-related lipid transfer proteins and homeobox-leucine zipper proteins.
Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation which is usually zinc, but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophillic role.
Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site []. The HEXXH motif is relatively common, but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases [].This group of metallopeptidases belong to the MEROPS peptidase family M17 (leucyl aminopeptidase family, clan MF), the type example being leucyl aminopeptidase from Bos taurus (Bovine). Aminopeptidases are exopeptidases involved in the processing and regular
turnover of intracellular proteins, although their precise role in cellularmetabolism is unclear [
,
]. Leucine aminopeptidases cleave leucine residues from the N-terminal of polypeptide chains, but substantial rates are evident for all amino acids [].The enzymes exist as homo-hexamers, comprising 2 trimers stacked on top of
one another []. Each monomer binds 2 zinc ions and folds into 2 alpha/beta-type quasi-spherical globular domains, producing a comma-like shape [
]. The N-terminal 150 residues form a 5-stranded β-sheet with 4 parallel and 1 anti-parallel strand sandwiched between 4 α-helices []. An α-helix extends into the C-terminal domain, which comprises a central 8-stranded saddle-shaped β-sheet sandwiched between groups of helices, forming the monomer hydrophobic core []. A 3-stranded β-sheet resides on the surface of the monomer, where it interacts with other members of the hexamer []. The two zinc ions and the active site are entirely located in the C-terminal catalytic domain [].
CG-1 domains are highly conserved domains of about 130 amino-acid residues containing a predicted bipartite nuclear localisation signal. They are named after a partial cDNA clone isolated from parsley encoding a sequence-specific DNA-binding protein [
]. CG-1 domains are found in CAMTA proteins (for CAlModulin -binding Transcription Activator), which are transcription factors containing a calmodulin-binding domain and ankyrin repeats [].
This family of proteins are functionally uncharacterised. This family is found in eukaryotes. Proteins in this family are about 70 amino acids in length.
Acyl-CoA dehydrogenases (
) are a family of flavoproteins that catalyse the alpha,beta-dehydrogenation of acyl-CoA thioesters to the corresponding trans 2,3-enoyl CoA-products with the concomitant reduction of enzyme-bound FAD. Different family members share a high sequence identity, catalytic mechanisms, and structural properties, but differ in the position of their catalytic bases and in their substrate binding specificity. Butyryl-CoA dehydrogenase [
] prefers short chain substrates, medium chain- and long-chain acyl-CoA dehydrogenases prefer medium and long chain substrates, respectively, and Isovaleryl-CoA dehydrogenase [] prefers branched-chain substrates.The monomeric enzyme is folded into three domains of approximately equal size, where the N-terminal domain is all-α, the middle domain is an open (5,8) barrel, and the C-terminal domain is a four-helical bundle. The constituent families differ in the numbers of C-terminal domains. This entry represents the N-terminal α-helical domain found in medium chain acyl-CoA dehydrogenases, as well as in the related peroxisomal acyl-CoA oxidase-II enzymes. Acyl-CoA oxidase (ACO;
) catalyses the first and rate-determining step of the peroxisomal beta-oxidation of fatty acids [
].
Acyl-CoA dehydrogenase/oxidase, N-terminal and middle domain superfamily
Type:
Homologous_superfamily
Description:
Acyl-CoA dehydrogenases (
) are a family of flavoproteins that catalyse the alpha,beta-dehydrogenation of acyl-CoA thioesters to the corresponding trans 2,3-enoyl CoA-products with the concomitant reduction of enzyme-bound FAD. Different family members share a high sequence identity, catalytic mechanisms, and structural properties, but differ in the position of their catalytic bases and in their substrate binding specificity. Butyryl-CoA dehydrogenase [
] prefers short chain substrates, medium chain- and long-chain acyl-CoA dehydrogenases prefer medium and long chain substrates, respectively, and Isovaleryl-CoA dehydrogenase [] prefers branched-chain substrates.The monomeric enzyme is folded into three domains of approximately equal size, where the N-terminal domain is all-α, the middle domain is an open (5,8) barrel, and the C-terminal domain is a four-helical bundle. The constituent families differ in the numbers of C-terminal domains. This superfamily represents both the N-terminal and middle domains found in medium chain acyl-CoA dehydrogenases, as well as in the related peroxisomal acyl-CoA oxidase-II enzymes. Acyl-CoA oxidase (ACO;
) catalyses the first and rate-determining step of the peroxisomal beta-oxidation of fatty acids [
].
Acyl-CoA dehydrogenases (
) are a family of flavoproteins that catalyse the alpha,beta-dehydrogenation of acyl-CoA thioesters to the corresponding trans 2,3-enoyl CoA-products with the concomitant reduction of enzyme-bound FAD. Different family members share a high sequence identity, catalytic mechanisms, and structural properties, but differ in the position of their catalytic bases and in their substrate binding specificity. Butyryl-CoA dehydrogenase [
] prefers short chain substrates, medium chain- and long-chain acyl-CoA dehydrogenases prefer medium and long chain substrates, respectively, and Isovaleryl-CoA dehydrogenase [] prefers branched-chain substrates.The monomeric enzyme is folded into three domains of approximately equal size, where the N-terminal domain is all-α, the middle domain is an open (5,8) barrel, and the C-terminal domain is a four-helical bundle. The constituent families differ in the numbers of C-terminal domains. This entry represents the middle β-barrel domain found in medium chain acyl-CoA dehydrogenases, as well as in the related peroxisomal acyl-CoA oxidase-II enzymes. Acyl-CoA oxidase (ACO;
) catalyses the first and rate-determining step of the peroxisomal beta-oxidation of fatty acids [
].
The Sac domain is a region of homology between the N terminus of synaptojanin and the otherwise unrelated yeast protein Sac1p. The Sac domain is approximately 400 residues in length, and proteins containing this domain show approximately 35% identity with other Sac domains throughout this region. The Sac domain exhibits phosphatidylinositol polyphosphate phosphatase activity and can hydrolyse phosphate from any of the three positions of inositol that may be phosphorylated (3-, 4- and 5). However, adjacent phosphates are resistant to hydrolysis. Sac domains cannot hydrolyse phosphate from phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2), or PtdIns(3,4)P2, or PtdIns(3,4,5)P3, but can hydrolyse PtdIns(3,5)P2 [
].The Sac domain consists of seven highly conserved motifs which appear to define the catalytic and regulatory regions of the phosphatase. The sixth conserved region contains a highly conserved C-x(5)-R-[TS] motif, thought to be the catalytic motif of many metal-independent protein and inositide polyphosphate phosphatases. Interestingly, the Inp51p Sac domain in which the cysteine, arginine and threonine/serine residues within the C-x(5)-R-[TS]motif are absent, does not exhibit any phosphatase activity [
].Two classes of Sac domain proteins have been identified in mammals as well as lower eukaryotes [
]. The first comprises proteins, which, in addition to an N-terminal phosphatase Sac domain, have all the domains associated with type II phosphatidylinositol phosphate 5-phosphatases:Mammalian synaptojanins, type II phosphatidylinositol phosphate 5- phosphatases.Yeast INP51, a 108kDa membrane protein. It is involved in endocytosis and regulation of the actin cytoskeleton under conditions of normal vegetative growth. Although the Sac phosphatase domain of INP51 may be catalytically inactive, the domain may retain other functions.Yeast INP52, a 133kDa membrane protein. It is involved in endocytosis and regulation of the actin cytoskeleton under conditions of normal vegetative growth.Yeast INP53, a 124kDa membrane protein. It appears to have a role in intra-Golgi and Golgi-to-endosomal trafficking.The other class of Sac-containing phosphatases consists of proteins with an N-terminal Sac phosphatase domain and no other recognizable domains:Yeast Sac1p, a 67kDa membrane protein found in the endoplasmic reticulum (ER) and Golgi. It regulates the actin cytoskeleton and phospholipid metabolism.Yeast FIG4, a 101kDa protein encoded by a pheromone regulated or induced gene. FIG4 might function to regulate effector molecules of the actin cytoskeleton during mating.
The CHASE domain is an extracellular domain of 200-230 amino acids, which is found in transmembrane receptors from bacteria, lower eukaryotes and plants. It has been named CHASE (Cyclases/Histidine kinases Associated Sensory Extracellular) because of its presence in diverse receptor-like proteins with histidine kinase and nucleotide cyclase domains. The CHASE domain always occurs N-terminally in extracellular or periplasmic locations, followed by an intracellular tail housing diverse enzymatic signalling domains such as histidine kinase (
), adenyl cyclase, GGDEF-type nucleotide cyclase and EAL-type phosphodiesterase domains, as well as non-enzymatic domains such PAS (
), GAF (
), phosphohistidine and response regulatory domains. The CHASE domain is predicted to bind diverse low molecular weight ligands, such as the cytokinin-like adenine derivatives or peptides, and mediate signal transduction through the respective receptors [
,
].The CHASE domain has a predicted alpha+beta fold, with two extended alpha helices on both boundaries and two central alpha helices separated by beta sheets. The termini are less conserved compared with the central part of the domain, which shows strongly conserved motifs.
Signal transduction histidine kinase, dimerisation/phosphoacceptor domain
Type:
Domain
Description:
This entry represents the dimerisation and phosphoacceptor domain found in some histidine kinases. Signal transducing histidine kinases are the key elements in two-component signal transduction systems, which control complex processes such as the initiation of development in microorganisms [
]. Examples of histidine kinases are EnvZ, which plays a central role in osmoregulation []. Histidine kinases usually have an N-terminal ligand-binding domain and a C-terminal kinase domain, but other domains may also be present. The kinase domain is responsible for the autophosphorylation of the histidine with ATP, the phosphotransfer from the kinase to an aspartate of the response regulator, and the phosphotransfer from aspartyl phosphate back to ADP or to water []. The homodimeric domain includes the site of histidine autophosphorylation and phosphate transfer reactions. The structure of the homodimeric domain comprises a closed, four-helical bundle with a left-handed twist, formed by two identical α-hairpin subunits [].
Signal transduction histidine kinase-related protein, C-terminal
Type:
Domain
Description:
Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions [
]. Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk []. These pathways have been adapted to response to a wide variety of stimuli, including nutrients, cellular redox state, changes in osmolarity, quorum signals, antibiotics, and more []. Two-component systems are comprised of a sensor histidine kinase (HK) and its cognate response regulator (RR) []. The HK catalyses its own auto-phosphorylation followed by the transfer of the phosphoryl group to the receiver domain on RR; phosphorylation of the RR usually activates an attached output domain, which can then effect changes in cellular physiology, often by regulating gene expression. Some HK are bifunctional, catalysing both the phosphorylation and dephosphorylation of their cognate RR. The input stimuli can regulate either the kinase or phosphatase activity of the bifunctional HK.A variant of the two-component system is the phospho-relay system. Here a hybrid HK auto-phosphorylates and then transfers the phosphoryl group to an internal receiver domain, rather than to a separate RR protein. The phosphoryl group is then shuttled to histidine phosphotransferase (HPT) and subsequently to a terminal RR, which can evoke the desired response [
,
].Signal transducing histidine kinases are the key elements in two-component signal transduction systems, which control complex processes such as the initiation of development in microorganisms [
,
]. Examples of histidine kinases are EnvZ, which plays a central role in osmoregulation [], and CheA, which plays a central role in the chemotaxis system []. Histidine kinases usually have an N-terminal ligand-binding domain and a C-terminal kinase domain, but other domains may also be present. The kinase domain is responsible for the autophosphorylation of the histidine with ATP, the phosphotransfer from the kinase to an aspartate of the response regulator, and (with bifunctional enzymes) the phosphotransfer from aspartyl phosphate back to ADP or to water []. The kinase core has a unique fold, distinct from that of the Ser/Thr/Tyr kinase superfamily. HKs can be roughly divided into two classes: orthodox and hybrid kinases [
,
]. Most orthodox HKs, typified by the Escherichia coli EnvZ protein, function as periplasmic membrane receptors and have a signal peptide and transmembrane segment(s) that separate the protein into a periplasmic N-terminal sensing domain and a highly conserved cytoplasmic C-terminal kinase core. Members of this family, however, have an integral membrane sensor domain. Not all orthodox kinases are membrane bound, e.g., the nitrogen regulatory kinase NtrB (GlnL) is a soluble cytoplasmic HK []. Hybrid kinases contain multiple phosphodonor and phosphoacceptor sites and use multi-step phospho-relay schemes instead of promoting a single phosphoryl transfer. In addition to the sensor domain and kinase core, they contain a CheY-like receiver domain and a His-containing phosphotransfer (HPt) domain.
This domain is present in many sensor proteins that respond to extra-cytoplasmic stimuli in bacteria, but is also found in many proteins of metazoan origin. Sensors are usually linked to a 2-component regulatory system consisting of the sensor and a cytoplasmic regulator protein [
].The cytoplasmic C-terminal portions of the sensor proteins show marked sequence similarity and are responsible for kinase activity [
]. Some sensor proteins are cytoplasmic and may respond to several external stimuli. Sensors also show similarity to some regulatory proteins []. The structure of CheA, a signal-transducing histidine kinase is known []. The catalytic domain consists of several α-helices packed over one face of a large anti-parallel beta sheet forming a loop which closes over the bound ATP. Hydrolysis of ATP is coupled to Mg2 release and conformational changes in the ATP-binding cavity.
This domain is found in several ATP-binding proteins, including: histidine kinase [
], DNA gyrase B, topoisomerases [], heat shock protein HSP90 [,
,
], phytochrome-like ATPases and DNA mismatch repair proteins. The fold of this domain consists of two layers, alpha/beta, which contains an 8-stranded mixed β-sheet.
Most prokaryotic signal-transduction systems and a few eukaryotic pathways use phosphotransfer schemes involving two conserved components, a histidine protein kinase (HK) and a response regulator protein (RR). The HK, which is regulated by environmental stimuli, autophosphorylates at a histidine residue, creating a high-energy phosphoryl group that is subsequently transferred to an aspartate residue in the RR domain. Phosphorylation induces a conformational change in RR that results in activation of an associated domain that effects the response.Both prokaryotic and eukaryotic HKs contain the same basic signaling components, namely a diverse sensing domain and a highly conserved kinase core that has a unique fold, distinct from that of the Ser/Thr/Tyr kinase superfamily. The overall activity of the kinase is modulated by input signals to the sensing domain. HKs undergo an ATP-dependent autophosphorylation at a conserved His residue in the kinase core. Autophosphorylation is a bimolecular reaction between homodimers, in which one HK monomer catalyzes the phosphorylation of the conserved His residue in the second monomer.The sensing domains are variable in sequence, reflective of the many different environmental signals to which HKs are responsive, whereas the about 250-residue kinase core is more conserved. The kinase core is composed of a dimerization domain and an ATP/ADP-binding phosphotransfer or catalytic domain and can be identified by five conserved primary sequence motifs present in both eukaryotic and prokaryotic HKs. These motifs have been termed the H, N, G1, F and G2 boxes. The conserved His substrate is the central feature in the H box, whereas the N, G1, F and G2 boxes define the nucleotide binding cleft. In most HKs, the H box is part of the dimerization domain. However, for some proteins, like CheA, the conserved His is located at the far N terminus of the protein in a separate HPt domain. The N, G1, F and G2 boxes are usually contiguous, but the spacing between these motifs is somewhat varied. The catalytic core forms an α-β sandwich consisting of five antiparallel beta strands and three alpha helices [,
,
].The entry represents the histidine kinase core.
This entry represent the main structural domain of NTF2 and related domains.Nuclear transport factor 2 (NTF2) is a homodimer which stimulates efficient nuclear import of a cargo protein. NTF2 binds to both RanGDP and FxFG repeat-containing nucleoporins. NTF2 folds into a cone with a deep hydrophobic cavity, the opening of which is surrounded by several negatively charged residues. RanGDP binds to NTF2 by inserting a conserved phenylalanine residue into the hydrophobic pocket of NTF2 and making electrostatic interactions with the conserved negatively charged residues that surround the cavity [
].
Ran (
) is an evolutionary conserved member of the Ras superfamily of small GTPases that regulates all receptor-mediated transport between the nucleus and the cytoplasm. Import receptors bind their cargos in the cytoplasm where the concentration of RanGTP is low and release their cargos in the nucleus where the concentration of RanGTP is high [
]. Export receptors respond to Ran GTP in the oppositemanner.
Nuclear transport factor 2 (NTF2) is a homodimer of approximately 14kDa subunits which stimulates efficient nuclear import of a cargo protein. NTF2 binds to both RanGDP and FxFG repeat-containing nucleoporins. NTF2 binds to RanGDP sufficiently strongly for the complex to remain intact during transport through NPCs, but the interaction between NTF2 and FxFG nucleoporins is much more transient, which would enable NTF2 to move through the NPC by hopping from one repeat to another [
,
].NTF2 folds into a cone with a deep hydrophobic cavity, the opening of which is surrounded by several negatively charged residues. RanGDP binds to NTF2 by inserting a conserved phenylalanine residue into the hydrophobic pocket of NTF2 and making electrostatic interactions with the conserved negatively charged residues that surround the cavity.This entry contains predominantly eukaryotic proteins. The following proteins contain a region similar to NTF2:
Eukaryotic NXF proteins []. These are nuclear mRNA export factors. These proteins contain, in addition to a NTF2 domain, a number of leucine-rich repeats and a UBA domain.Eukaryotic NXT1/NXT2 proteins [
]. These proteins are stimulators of protein export for NES-containing proteins. The also play a role in mRNA nuclear export. They heterodimerize with NFX proteins. In contrast to NTF2, NXT1 and NXT2 preferentially bind RanGTP.Eukaryotic Ras-GTPase-activating protein (GAP)-binding proteins (G3BP's). These proteins contain one NTF2 domain and one RRM (see
).
Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [
,
,
,
,
]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few []. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target. This entry represents MYND-type zinc finger domains. The MYND domain (myeloid, Nervy, and DEAF-1) is present in a large group of proteins that includes RP-8 (PDCD2), Nervy, and predicted proteins from Drosophila, mammals, Caenorhabditis elegans, yeast, and plants [
,
,
]. The MYND domain consists of a cluster of cysteine and histidine residues, arranged with an invariant spacing to form a potential zinc-binding motif []. Mutating conserved cysteine residues in the DEAF-1 MYND domain does not abolish DNA binding, which suggests that the MYND domain might be involved in protein-protein interactions []. Indeed, the MYND domain of ETO/MTG8 interacts directly with the N-CoR and SMRT co-repressors [,
]. Aberrant recruitment of co-repressor complexes and inappropriate transcriptionalrepression is believed to be a general mechanism of leukemogenesis caused by the t(8;21) translocations that fuse ETO with the acute myelogenous leukemia 1 (AML1) protein. ETO has been shown to be a co-repressor recruited by the promyelocytic leukemia zinc finger (PLZF) protein [
]. Adivergent MYND domain present in the adenovirus E1A binding protein BS69 was also shown to interact with N-CoR and mediate transcriptional repression [
]. The current evidence suggests that the MYND motif in mammalian proteins constitutes a protein-protein interaction domain that functions as a co-repressor-recruiting interface.
This entry contains Serp1/Serp2 and yeast Ysy6 stress-associated endoplasmic reticulum proteins. In humans, Serp1 (also known as RAMP4) interacts with target proteins during their translocation into the lumen of the endoplasmic reticulum. It has also been shown to protect unfolded target proteins against degradation during ER stress. It may facilitate glycosylation of target proteins after termination of ER stress and may modulate the use of N-glycosylation sites on target proteins [
,
].
Chloroplast function requires the import of nuclear encoded proteins from the cytoplasm across the chloroplast double membrane. This is accompished by two protein complexes, the Toc complex located at the outer membrane and the Tic complex loacted at the inner membrane [
]. The Toc complex recognises specific proteins by a cleavable N-terminal sequence and is primarily responsible for translocation through the outer membrane, while the Tic complex translocates the protein through the inner membrane.This entry represents Tic22, a core member of the Tic complex. Tic22 is a soluble protein and the only Tic complex component of the intermembrane space that has been shown to interact with preproteins during import. It may also act as a chaperone that prevent misfolding or missorting of the preprotein to the intermembrane space and potentially serve as a component that links the Toc and Tic complexes [
].
O-Glycosyl hydrolases (
) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families [
,
]. This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.Glycoside hydrolase family 16
comprises enzymes with a number of known activities; lichenase (
); xyloglucan xyloglucosyltransferase (
); agarase (
); kappa-carrageenase (
); endo-beta-1,3-glucanase (
); endo-beta-1,3-1,4-glucanase (
); endo-beta-galactosidase (
).
This entry represents a group of ubiquitin-like-conjugating enzymes, including Atg3 and Atg10.Atg3 is the E2 enzyme for the LC3 lipidation process [
]. It is essential for autophagocytosis. The super protein complex, the Atg16L complex, consists of multiple Atg12-Atg5 conjugates. Atg16L has an E3-like role in the LC3 lipidation reaction. The activated intermediate, LC3-Atg3 (E2), is recruited to the site where the lipidation takes place []. Atg3 catalyses the conjugation of Atg8 and phosphatidylethanolamine (PE). Atg3 has an α/β-fold, and its core region is topologically similar to canonical E2 enzymes. Atg3 has two regions inserted in the core region and another with a long α-helical structure that protrudes from the core region as far as 30 A [
]. It interacts with Atg8 through an intermediate thioester bond between Cys-288 and the C-terminal Gly of Atg8. It also interacts with the C-terminal region of the E1-like Atg7 enzyme.Atg10 acts as an E2-like enzyme that catalyzes the conjugation of ATG12 to ATG5 [].
This entry represents a group of conserved proteins from fungi, plants to animals. They are transmembrane proteins. Proteins in this entry include budding yeast Erv14/15, Drosophila Cornichon and human CNIH1/2/3/4. The drosophila cornichon protein (gene: cni), the founding member of this family, is an integral component of the COPII-coated vesicles that mediate cargo export from the yeast endoplasmic reticulum (ER) [
]. It is required in the germline for dorsal-ventral signalling. The dorsal-ventral pattern formation involves a reorganisation of the microtubule network correlated with the movement of the oocyte nucleus, and depending on the initial correct establishment of the anterior-posterior axis via a signal from the oocyte produced by cornichon and gurken and received by torpedo protein in the follicle cells []. Erv14 is a COPII-coated vesicle protein involved in vesicle formation and incorporation of specific secretory cargo. It is required for axial budding [
,
].CNIH1 is involved in the selective transport and maturation of TGF-alpha family proteins [
].
Asymmetric lipid distribution is a fundamental characteristic of biological lipid bilayers, one such axample is the translocation of the Man
5GlcNAc
2-PP-Dol intermediate from the cytosolic side of the ER membrane to the lumen before the completion of the biosynthesis of Glc
3Man
9GlcNAc
2-PP-Dol [
]. RFT1 encodes an evolutionarily conserved protein required for this translocation.
This entry represents a three-layer alpha/beta/alpha domain found as the catalytic domain at the C-terminal in homotetrameric tRNA-intron endonucleases [
], and as domains 2 and 4 (C-terminal) in the homodimeric enzymes []. tRNA-intron endonucleases () remove tRNA introns by cleaving pre-tRNA at the 5'- and 3'-splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3' cyclic phosphate and 5'-hydroxyl termini [
]. These enzymes recognise a pseudosymmetric substrate in which two bulged loops of three bases are separated by a stem of four bp []. Although homotetrameric enzymes contain four active sites, only two participate in the cleavage, and should therefore, be considered as a dimer of dimers.
This superfamily represents a structural domain found in three types of endonucleases: TsnA endonuclease (N-terminal) [
], Hjc-type resolvase [], and tRNA-intron endonuclease (C-terminal) () [
]. These domains have a 3-layer α/β/α topology, which is similar in structure to a motif found in several restriction endonucleases.TsnA endonuclease is a catalytic component of the Tn7 transposition system. Tn7 transposase is composed of four proteins: TnsA, TnsB, TnsC and TsnD. DNA breakage at the 5' end of the transposon is carried out by TnsA, and breakage and joining at the 3' end is carried out by TnsB. TnsC is the molecular switch that regulates transposition. The N-terminal domain of TnsA is catalytic.Hjc is a type of Holliday junction resolvase. The Holliday junction is an essential intermediate of homologous recombination, comprising four-stranded DNA complexes that are formed during recombination and related DNA repair events. During homologous recombination, genetic information is physically exchanged between parental DNAs via crossing single strands of the same polarity within the four-way Holliday structure. Hjc is an archaeal endonuclease, which specifically resolves the junction DNA to produce two separate recombinant DNA duplexes. This process is terminated by the endonucleolytic activity of resolvases, which convert the four-way DNA back to two double strands. tRNA-intron endonucleases cleave pre-tRNA producing 5'-hydroxyl and 2',3'-cyclic phosphate termini, and specifically removing the intron. The splicing of transfer RNA precursors is similar in Eukarya and Archaea. In both kingdoms an endonuclease recognises the splice sites and releases the intron, but the mechanism of splice site recognition is different in each kingdom.
The photolyase/cryptochrome family consists of flavoproteins that perform
various functions using blue-light photons as an energie source. It is presentin all three domains of life, that is, archaea, eubacteria, and eukaryotes,
and hence has arisen very early during evolution to protect genomes againstthe genotoxic effects of ultraviolet light originating from the sun. The
photolyase/cryptochrome family is divided into two major groups: photolyasesand cryptochromes. Photolyases repair
cytotoxic and mutagenic UV-induced photolesions in DNA in many species frombacteria to plants and animals by using a light-dependent repair mechanism. It
involves light absorption, electron transfer from an excited reduced anddeprotanated FADH(-) to the flipped-out photolesion, followed by the
fragmentation of the photolesions. Cryptochromes are highly related proteinsthat generally no longer repair damaged DNA, but function as photoreceptors.
Cryptochromes regulate growth and development in plants and the circadianclock in animals [
,
,
,
,
,
,
].Both photolyases and cryptochromes have a bilobal architecture consisting of
two domains: an N-terminal alpha/beta domain that may contain a light-harvesting chromophore to additionally broaden their activity spectra and a C-
terminal α-helical catalytic domain comprising the light-sensitive FADcofactor. Diverse classes of antenna chromophores likes 5,10-
methenyltetrahydrofolate (MTHF), 8-hydroxydeazaflavin, FMN or FAD have beenidentified in some photolyase/cryptochrome to broaden their activity spectra,
whereas many others apparently lack any bound antenna chromophores.This entry represents the photolyase/cryptochrome alpha/beta domain. It adopts a dinucleotide binding fold with a five-stranded parallel beta sheet flanked on both sides by alpha helices [
,
].
Proteinase propeptide inhibitors (sometimes refered to as activation peptides) are responsible for the modulation of folding and activity of the pro-enzyme or zymogen. The pro-segment docks into the enzyme moiety shielding the substrate binding site, thereby promoting inhibition of the enzyme. Several such propeptides share a similar topology [
], despite often low sequence identities []. The propeptide region has an open-sandwich antiparallel-α/antiparallel-β fold, with two α-helices and four β-strands with a (β/α/β)x2 topology.This entry represents the propeptide domain at the N terminus of peptidases belonging to MEROPS family S8A, subtilisins. The subtilisin propeptides are known to function as molecular chaperones, assisting in the folding of the mature peptidase [
]. The propeptide is removed by proteolytic cleavage; removal activating the enzyme. This domain is also found in members of MEROPS proteinase inhibitor family I9.
The PA (Protease associated) domain is found as an insert domain in diverse proteases, which include the MEROPS peptidase families A22B, M28, and S8A [
]. The PA domain is also found in a plant vacuolar sorting receptor and members of the RZF family, e.g.
. It has been suggested that this domain forms a lid-like structure that covers the active site in active proteases, and is involved in protein recognition in vacuolar sorting receptors [
].
This entry represents a domain found in plant transcription factors, including TGA proteins and protein PERIANTHIA. In Arabidopsis thaliana, there are seven TGA paralogues (TGA 1-7), which are transcriptional activators that binds specifically to the DNA sequence 5'-TGACG-3' [
,
]. Another Arabidopsis thaliana protein in this entry, PERIANTHIA, binds to the 5'-AAGAAT-3' cis-acting element found in AG promoter and is involved in the determination of floral organ number [].
This domain is found at the C terminus of phosphoribosyltransferases and phosphoribosyltransferase-like proteins. It contains putative transmembrane regions. It often appears together with calcium-ion dependent C2 domains (
).
The GDP dissociation inhibitor for rho proteins, rho GDI, regulates GDP/GTP exchange by inhibiting the dissociation of GDP from them. The protein contains 204 amino acids, with a calculated Mr value of 23,421. Hydropathy analysis shows it to be largely hydrophilic, with a single hydrophobic region. The protein plays an important role in the activation of the superoxide (O2-)-generating NADPH oxidase of phagocytes. This process requires the interaction of membrane-associated cytochrome b559 with 3 cytosolic components: p47-phox, p67-phox and a heterodimer of the small G-protein p21rac1 and rho GDI [
]. The association of p21rac and GDI inhibits dissociation of GDP from p21rac, thereby maintaining it in an inactive form. The proteins are attached via a lipid tail on p21rac that binds to the hydrophobic region of GDI []. Dissociation of these proteins might be mediated by the release of lipids (e.g., arachidonate and phosphatidate) from membranes through the action of phospholipases []. The lipids may then compete with the lipid tail on p21rac for the hydrophobic pocket on GDI.Two homologues of rho GDP-dissociation inhibitors have been identified in Dicytostelium: GDI1 and GDI2. They are cytosolic proteins. GDI1 has been found to play a central role in cytokinesis through the regulation of Rho family GTPases Rac1s and/or RacE [
,
].Rho GDI in yeast has been shown to have similar properties as mammalian rho GDI [
].
The GDP dissociation inhibitor for rho proteins, rho GDI, regulates GDP/GTP exchange by inhibiting the dissociation of GDP from them. The protein contains 204 amino acids, with a calculated Mr value of 23,421. Hydropathy analysis shows it to be largely hydrophilic, with a single hydrophobic region. The protein plays an important role in the activation of the superoxide (O2-)-generating NADPH oxidase of phagocytes. This process requires the interaction of membrane-associated cytochrome b559 with 3 cytosolic components: p47-phox, p67-phox and a heterodimer of the small G-protein p21rac1 and rho GDI [
]. The association of p21rac and GDI inhibits dissociation of GDP from p21rac, thereby maintaining it in an inactive form. The proteins are attached via a lipid tail on p21rac that binds to the hydrophobic region of GDI []. Dissociation of these proteins might be mediated by the release of lipids (e.g., arachidonate and phosphatidate) from membranes through the action of phospholipases []. The lipids may then compete with the lipid tail on p21rac for the hydrophobic pocket on GDI.Two homologues of rho GDP-dissociation inhibitors have been identified in Dicytostelium: GDI1 and GDI2. They are cytosolic proteins. GDI1 has been found to play a central role in cytokinesis through the regulation of Rho family GTPases Rac1s and/or RacE [
,
].Rho GDI in yeast has been shown to have similar properties as mammalian rho GDI [
].The rhoGDI structural domain contains both a structured, immunoglobulin-like fold, and a highly flexible N terminus of 50-60 residues [
]. The N-terminal region becomes ordered upon complex formation and contributes more than 60% to the interface area [].
Leucine-rich repeats (LRR) consist of 2-45 motifs of 20-30 amino acids in length that generally folds into an arc or horseshoe shape [
]. LRRs occur in proteins ranging from viruses to eukaryotes, and appear to provide a structural framework for the formation of protein-protein interactions [,
].Proteins containing LRRs include tyrosine kinase receptors, cell-adhesion molecules, virulence factors, and extracellular matrix-binding glycoproteins, and are involved in a variety of biological processes, including signal transduction, cell adhesion, DNA repair, recombination, transcription, RNA processing, disease resistance, apoptosis, and the immune response [,
].Sequence analyses of LRR proteins suggested the existence of several different subfamilies of LRRs. The significance of this classification is that repeats from different subfamilies never occur simultaneously and have most probably evolved independently. It is, however, now clear that all major classes of LRR have curved horseshoe structures with a parallel beta sheet on the concave side and mostly helical elements on the convex side. At least six families of LRR proteins, characterised by different lengths and consensus sequences of the repeats, have been identified. Eleven-residue segments of the LRRs (LxxLxLxxN/CxL), corresponding to the β-strand and adjacent loop regions, are conserved in LRR proteins, whereas the remaining parts of the repeats (herein termed variable) may be very different. Despite the differences, each of the variable parts contains two half-turns at both ends and a "linear"segment (as the chain follows a linear path overall), usually formed by a helix, in the middle. The concave face and the adjacent loops are the most common protein interaction surfaces on LRR proteins.
3D structure of some LRR proteins-ligand complexes show that the concave surface of LRR domain is ideal for interaction with α-helix, thus supporting earlier conclusions that the elongated and curved LRR structure provides an outstanding framework for achieving diverse protein-protein interactions []. Molecular modeling suggests that the conserved pattern LxxLxL, which is shorter than the previously proposed LxxLxLxxN/CxL is sufficient to impart the characteristic horseshoe curvature to proteins with 20- to 30-residue repeats []. This is a cysteine-containing, leucine-rich repeat which is wide spread amongst
eukaryotes proteins but does not appear to be found in archae, bacteria or viruses.
This domain is found at the N terminus of structural maintenance of chromosomes (SMC) proteins, which function together with other proteins in a range of chromosomal transactions, including chromosome condensation, sister-chromatid cohesion, recombination, DNA repair and epigenetic silencing of gene expression [
]. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics []. This domain is also found in RecF and RecN proteins, which are involved in DNA metabolism and recombination.
This entry represents the hinge region of the SMC (Structural Maintenance of Chromosomes) family of proteins. The hinge region is responsible for formation of the DNA interacting dimer. It is also possible that its precise structure is an essential determinant of the specificity of the DNA-protein interaction [
].
Molecular chaperones, or heat shock proteins (Hsps) are ubiquitous proteins that act to maintain proper protein folding within the cell [
]. They assist in the folding of nascent polypeptide chains, and are also involved in the re-folding of denatured proteins following proteotoxic stress. As their name implies, the heat shock proteins were first identified as proteins that were up-regulated under conditions of elevated temperature. However, subsequent studies have shown that increased Hsp expression is induced by a variety of cellular stresses, including oxidative stress and inflammation. Five major Hsp families have been determined, and are categorized according to their molecular size (Hsp100, Hsp90, Hsp70, Hsp60, and the small Hsps). Hsps are involved in a variety of cellular processes that are ATP-dependent. These include: prevention of protein aggregation, protein degradation, protein trafficking, and maintenance of signalling proteins in a conformation that permits activation.
Hsp90 chaperones are unique in their ability to regulate a specific subset of cellular signalling proteins that have been implicated in disease processes, including intracellular protein kinases, steroid hormone receptors, and growth factor receptors [
].
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 [
,
].Evidence suggests that, in prokaryotes, the peptidyl transferase reaction is performed by the large subunit 23S rRNA, whereas proteins probably have a greater role in eukaryotic ribosomes. Most of the proteins lie close to, or on the surface of, the 30S subunit, arranged peripherally around the rRNA [
]. The small subunit ribosomal proteins can be categorised as primary binding proteins, which bind directly and independently to 16S rRNA; secondary binding proteins, which display no specific affinity for 16S rRNA, but its assembly is contingent upon the presence of one or more primary binding proteins; and tertiary binding proteins, which require the presence of one or more secondary binding proteins and sometimes other tertiary binding proteins.The small ribosomal subunit protein S10 consists of about 100 amino acid residues. In Escherichia coli, S10 is involved in binding tRNA to the ribosome, and also operates as a transcriptional elongation factor [
]. Experimental evidence [] has revealed that S10 has virtually no groups exposed on the ribosomal surface, and is one of the "split proteins": these are a discrete group that are selectively removed from 30S subunits under low salt conditions and are required for the formation of activated 30S reconstitution intermediate (RI*) particles. S10 belongs to a family of proteins [
] that includes: bacteria S10; algal chloroplast S10; cyanelle S10; archaebacterial S10; Marchantia polymorpha and Prototheca wickerhamii mitochondrial S10; Arabidopsis thaliana mitochondrial S10 (nuclear encoded); vertebrate S20; plant S20; and yeast URP2.
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 [
,
].Evidence suggests that, in prokaryotes, the peptidyl transferase reaction is performed by the large subunit 23S rRNA, whereas proteins probably have a greater role in eukaryotic ribosomes. Most of the proteins lie close to, or on the surface of, the 30S subunit, arranged peripherally around the rRNA [
]. The small subunit ribosomal proteins can be categorised as primary binding proteins, which bind directly and independently to 16S rRNA; secondary binding proteins, which display no specific affinity for 16S rRNA, but its assembly is contingent upon the presence of one or more primary binding proteins; and tertiary binding proteins, which require the presence of one or more secondary binding proteins and sometimes other tertiary binding proteins.The small ribosomal subunit protein S10 consists of about 100 amino acid residues. In Escherichia coli, S10 is involved in binding tRNA to the ribosome, and also operates as a transcriptional elongation factor [
]. Experimental evidence [] has revealed that S10 has virtually no groups exposed on the ribosomal surface, and is one of the "split proteins": these are a discrete group that are selectively removed from 30S subunits under low salt conditions and are required for the formation of activated 30S reconstitution intermediate (RI*) particles. S10 belongs to a family of proteins [
] that includes: bacteria S10; algal chloroplast S10; cyanelle S10; archaebacterial S10; Marchantia polymorpha and Prototheca wickerhamii mitochondrial S10; Arabidopsis thaliana mitochondrial S10 (nuclear encoded); vertebrate S20; plant S20; and yeast URP2.
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 model describes the archaeal ribosomal protein and its equivalents in eukaryotes.
Evidence suggests that, in prokaryotes, the peptidyl transferase reaction is performed by the large subunit 23S rRNA, whereas proteins probably have a greater role in eukaryotic ribosomes. Most of the proteins lie close to, or on the surface of, the 30S subunit, arranged peripherally around the rRNA [
]. The small subunit ribosomal proteins can be categorised as primary binding proteins, which bind directly and independently to 16S rRNA; secondary binding proteins, which display no specific affinity for 16S rRNA, but its assembly is contingent upon the presence of one or more primary binding proteins; and tertiary binding proteins, which require the presence of one or more secondary binding proteins and sometimes other tertiary binding proteins.The small ribosomal subunit protein S10 consists of about 100 amino acid residues. In Escherichia coli, S10 is involved in binding tRNA to the ribosome, and also operates as a transcriptional elongation factor [
]. Experimental evidence [] has revealed that S10 has virtually no groups exposed on the ribosomal surface, and is one of the "split proteins": these are a discrete group that are selectively removed from 30S subunits under low salt conditions and are required for the formation of activated 30S reconstitution intermediate (RI*) particles. S10 belongs to a family of proteins [
] that includes: bacteria S10; algal chloroplast S10; cyanelle S10; archaebacterial S10; Marchantia polymorpha and Prototheca wickerhamii mitochondrial S10; Arabidopsis thaliana mitochondrial S10 (nuclear encoded); vertebrate S20; plant S20; and yeast URP2.
Prokaryotes and eukaryotes respond to heat shock and other forms of
environmental stress by inducing synthesis of heat-shock proteins (hsp) []. The 90kDa heat shock protein, Hsp90, is one of the most abundant proteins in eukaryotic cells, comprising 1-2% of cellular proteins under non-stress conditions []. Its contribution to various cellular processes including signal transduction, protein folding, protein degradation and morphological evolution has been extensively studied [,
]. The full functional activity of Hsp90 is gained in concert with other co-chaperones, playing an important role in the folding of newly synthesised proteins and stabilisation and refolding of denatured proteins after stress. Apart from its co-chaperones, Hsp90 binds to an array of client proteins, where the co-chaperone requirement varies and depends on the actual client. The
sequences of hsp90s show a distinctive domain structure, with a highly-conserved N-terminal domain separated from a conserved, acidic C-terminaldomain by a highly-acidic, flexible linker region.
Prokaryotes and eukaryotes respond to heat shock and other forms of environmental stress by inducing synthesis of heat-shock proteins (hsp) [
]. The 90kDa heat shock protein, Hsp90, is one of the most abundant proteins in eukaryotic cells, comprising 1-2% of cellular proteins under non-stress conditions []. Its contribution to various cellular processes including signal transduction, protein folding, protein degradation and morphological evolution has been extensively studied [,
]. The full functional activity of Hsp90 is gained in concert with other co-chaperones, playing an important role in the folding of newly synthesised proteins and stabilisation and refolding of denatured proteins after stress. Apart from its co-chaperones, Hsp90 binds to an array of client proteins, where the co-chaperone requirement varies and depends on the actual client. The
sequences of hsp90s show a distinctive domain structure, with a highly-conserved N-terminal domain separated from a conserved, acidic C-terminaldomain by a highly-acidic, flexible linker region.The signature pattern for the hsp90 family of proteins is located in a highly conserved region found in the N-terminal part of these proteins.
The membrane attack complex/perforin (MACPF) domain is conserved in bacteria, fungi, mammals and plants. It was originally identified and named as being common to five complement components (C6, C7, C8-alpha, C8-beta, and C9) and perforin. These molecules perform critical functions in innate and adaptive immunity. The MAC family proteins and perforin are known to participate in lytic pore formation. In response to pathogen infection, a sequential and highly specific interaction between the constituent elements occurs to form transmembrane channels which are known as the membrane-attack complex (MAC).Only a few other MACPF proteins have been characterised and several are thought to form pores for invasion or protection [
,
,
]. Examples are proteins from malarial parasites [], the cytolytic toxins from sea anemones [], and proteins that provide plant immunity [,
]. Functionally uncharacterised MACPF proteins are also evident in pathogenic bacteria such as Chlamydia spp [] and Photorhabdus luminescens (Xenorhabdus luminescens) [].The MACPF domain is commonly found to be associated with other N- and C-terminal domains, such as TSP1 (see
), LDLRA (see
), EGF-like (see
),Sushi/CCP/SCR (see
), FIMAC or C2 (see
). They probably control or target MACPF function [
,
]. The MACPF domain oligomerizes, undergoes conformational change, and is required for lytic activity.The MACPF domain consists of a central kinked four-stranded antiparallel beta sheet surrounded by alpha helices and beta strands, forming two structural segments. Overall, the MACPF domain has a thin L-shaped appearance. MACPF domains exhibit limited sequence similarity but contain a signature [YW]-G-[TS]-H-[FY]-x(6)-G-G motif [,
,
].Some proteins known to contain a MACPF domain are listed below:Vertebrate complement proteins C6 to C9. Complement factors C6 to C9 assemble to form a scaffold, the membrane attack complex (MAC), that permits C9 polymerisation into pores that lyse Gram-negative pathogens [
,
].Vertebrate perforin. It is delivered by natural killer cells and cytotoxic T lymphocytes and forms oligomeric pores (12 to 18 monomers) in the plasma membrane of either virus-infected or transformed cells.Arabidopsis thaliana (Mouse-ear cress) constitutively activated cell death 1 (CAD1) protein. It is likely to act as a mediator that recognises plant signals for pathogen infection [
].Arabidopsis thaliana (Mouse-ear cress) necrotic spotted lesions 1 (NSL1) protein [
].Venomous sea anemone Phyllodiscus semoni (Night anemone) toxins PsTX-60A and PsTX-60B [
].Venomous sea anemone Actineria villosa (Okinawan sea anemone) toxin AvTX-60A [
].Plasmodium sporozoite microneme protein essential for cell traversal 2 (SPECT2). It is essential for the membrane-wounding activity of the sporozoite and is involved in its traversal of the sinusoidal cell layer prior to hepatocyte-infection [
].P. luminescens Plu-MACPF. Although nonlytic, it was shown to bind to cell membranes [
].Chlamydial putative uncharacterised protein CT153 [
].
This domain is found in Lsm (like-Sm) proteins, which have a core structure consisting of an open β-barrel with an SH3-like topology.Lsm (like-Sm) proteins have diverse functions, and are thought to be important modulators of RNA biogenesis and function [
,
]. The Sm proteins form part of specific small nuclear ribonucleoproteins (snRNPs) that are involved in the processing of pre-mRNAs to mature mRNAs, and are a major component of the eukaryotic spliceosome. Most snRNPs consist of seven Sm proteins (B/B', D1, D2, D3, E, F and G) arranged in a ring on a uridine-rich sequence (Sm site), plus a small nuclear RNA (snRNA) (either U1, U2, U5 or U4/6) []. All Sm proteins contain a common sequence motif in two segments, Sm1 and Sm2, separated by a short variable linker []. Other snRNPs, such as U7 snRNP, can contain different Lsm proteins.Lsm proteins are also found in archaebacteria, which do not have any splicing apparatus, suggesting a more general role for Lsm proteins. Archaeal Lsm proteins have been shown to bind to small RNAs and are probably involved in many cellular processes [
]. Archaeal Lsm proteins are likely to represent the ancestral Lsm domain [].
This entry represents Sm-like protein Lsm7. It could be found in the nuclear Lsm2-8 complex or in the cytoplasmic Lsm1-7 complex. The Lsm2-8 complex associates with multiple snRNP complexes containing the U6 snRNA (U4/U6 snRNP, U4/U6.U5 snRNP, and free U6 snRNP). It binds and stabilizes the 3'-terminal poly(U) tract of U6 snRNA and facilitates the assembly of U4-U6 di-snRNP and U4-U6-U5 tri-snRNP [
,
,
]. The Lsm1-7 complex associates with deadenylated mRNA and promotes decapping in the 5'-3' mRNA decay pathway [,
]. The Sm and the Lsm proteins, characterised by the Sm-domain, have RNA-related functions. The Sm heptamer ring associates with four (U1, U2, U4, U5) snRNPs, while Lsm2-8 heptamer is part of the U6 snRNP. Another Lsm heptameric complex, Lsm1-7, which differs from Lsm2-8 by one Lsm protein, functions in mRNA decapping, a crucial step in the mRNA degradation pathway [
].
Amidase signature (AS) enzymes are a large group of hydrolytic enzymes that contain a conserved stretch of approximately 130 amino acids known as the AS sequence. They are widespread, being found in both prokaryotes and eukaryotes. AS enzymes catalyse the hydrolysis of amide bonds (CO-NH2), although the family has diverged widely with regard to substrate specificity and function. Nonetheless, these enzymes maintain a core alpha/beta/alpha structure, where the topologies of the N- and C-terminal halves are similar. AS enzymes characteristically have a highly conserved C-terminal region rich in serine and glycine residues, but devoid of aspartic acid and histidine residues, therefore they differ from classical serine hydrolases. These enzymes posses a unique, highly conserved Ser-Ser-Lys catalytic triad used for amide hydrolysis, although the catalytic mechanism for acyl-enzyme intermediate formation can differ between enzymes [
].Examples of AS enzymes include:Peptide amidase (Pam) [
], which catalyses the hydrolysis of the C-terminal amide bond of peptides.Fatty acid amide hydrolases [
], which hydrolyse fatty acid amid substrates (e.g. cannabinoid anandamide and sleep-inducing oleamide), thereby controlling the level and duration of signalling induced by this diverse class of lipid transmitters.Malonamidase E2 [
], which catalyses the hydrolysis of malonamate into malonate and ammonia, and which is involved in the transport of fixed nitrogen from bacteroids to plant cells in symbiotic nitrogen metabolism.Subunit A of Glu-tRNA(Gln) amidotransferase [
],a heterotrimeric enzyme that catalyses the formation of Gln-tRNA(Gln) by the transamidation of misacylated Glu-tRNA(Gln) via amidolysis of glutamine.The amidase signature enzymes consist structurally of a core domain that is covered by α-helices [
].
Amidase signature (AS) enzymes are a large group of hydrolytic enzymes that contain a conserved stretch of approximately 130 amino acids known as the AS sequence. They are widespread, being found in both prokaryotes and eukaryotes. AS enzymes catalyse the hydrolysis of amide bonds (CO-NH2), although the family has diverged widely with regard to substrate specificity and function. Nonetheless, these enzymes maintain a core alpha/beta/alpha structure, where the topologies of the N- and C-terminal halves are similar. AS enzymes characteristically have a highly conserved C-terminal region rich in serine and glycine residues, but devoid of aspartic acid and histidine residues, therefore they differ from classical serine hydrolases. These enzymes posses a unique, highly conserved Ser-Ser-Lys catalytic triad used for amide hydrolysis, although the catalytic mechanism for acyl-enzyme intermediate formation can differ between enzymes [
].Examples of AS enzymes include:Peptide amidase (Pam) [
], which catalyses the hydrolysis of the C-terminal amide bond of peptides.Fatty acid amide hydrolases [
], which hydrolyse fatty acid amid substrates (e.g. cannabinoid anandamide and sleep-inducing oleamide), thereby controlling the level and duration of signalling induced by this diverse class of lipid transmitters.Malonamidase E2 [
], which catalyses the hydrolysis of malonamate into malonate and ammonia, and which is involved in the transport of fixed nitrogen from bacteroids to plant cells in symbiotic nitrogen metabolism.Subunit A of Glu-tRNA(Gln) amidotransferase [
],a heterotrimeric enzyme that catalyses the formation of Gln-tRNA(Gln) by the transamidation of misacylated Glu-tRNA(Gln) via amidolysis of glutamine.
Kinesin [
,
,
] is a microtubule-associated force-producing protein that may play a role in organelle transport. The kinesin motor activity is directed toward the microtubule's plus end. Kinesin is an oligomeric complex composed of two heavy chains and two light chains. The maintenance of the quaternary structure does not require interchain disulphide bonds.The heavy chain is composed of three structural domains: a large globular N-terminal domain which is responsible for the motor activity of kinesin (it is known to hydrolyse ATP, to bind and move on microtubules), a central α-helical coiled coil domain that mediates the heavy chain dimerisation; and a small globular C-terminal domain which interacts with other proteins (such as the kinesin light chains), vesicles and membranous organelles.The kinesin motor domain comprises five motifs, namely N1 (P-loop), N2 (Switch I), N3 (Switch II), N4 and L2 (KVD finger) [
]. It has a mixed eight stranded β-sheet core with flanking solvent exposed α-helices and a small three-stranded antiparallel β-sheet in the N-terminal region [].A number of proteins have been recently found that contain a domain similar to that of the kinesin 'motor' domain [
,
]:Drosophila melanogaster claret segregational protein (ncd). Ncd is required for normal chromosomal segregation in meiosis, in females, and in early mitotic divisions of the embryo. The ncd motor activity is directed toward the microtubule's minus end.Homo sapiens CENP-E [
]. CENP-E is a protein that associates with kinetochores during chromosome congression, relocates to the spindle midzone at anaphase, and is quantitatively discarded at the end of the cell division. CENP-E is probably an important motor molecule in chromosome movement and/or spindle elongation.H. sapiens mitotic kinesin-like protein-1 (MKLP-1), a motor protein whose activity is directed toward the microtubule's plus end.Saccharomyces cerevisiae KAR3 protein, which is essential for nuclear fusion during mating. KAR3 may mediate microtubule sliding during nuclear fusion and possibly mitosis.S. cerevisiae CIN8 and KIP1 proteins which are required for the assembly of the mitotic spindle. Both proteins seem to interact with spindle microtubules to produce an outwardly directed force acting upon the poles.Emericella nidulans (Aspergillus nidulans) bimC, which plays an important role in nuclear division.A. nidulans klpA.Caenorhabditis elegans unc-104, which may be required for the transport of substances needed for neuronal cell differentiation.C. elegans osm-3.Xenopus laevis Eg5, which may be involved in mitosis.Arabidopsis thaliana KatA, KatB and katC.Chlamydomonas reinhardtii FLA10/KHP1 and KLP1. Both proteins seem to play a role in the rotation or twisting of the microtubules of the flagella.C. elegans hypothetical protein T09A5.2.The kinesin motor domain is located in the N-terminal part of most of the above proteins, with the exception of KAR3, klpA, and ncd where it is located in the C-terminal section.The kinesin motor domain contains about 330 amino acids. An ATP-binding motif of type A is found near position 80 to 90, the C-terminal half of the domain is involved in microtubule-binding.The signature pattern for this entry is derived from a conserved decapeptide inside the microtubule-binding region.
This domain is very short and is found at the N-terminal of many Gag-pol polyproteins from retrotransposons and related sequences. There is a highly conserved YxxWxxxM sequence motif.
This entry represents the glycosyltransferase family 92 [
,
,
]. The aligned region contains several conserved cysteine residues and several charged residues that may be catalytic residues. This is supported by the inclusion of this family in the GT-A glycosyl transferase superfamily.
This entry represents the C terminus of the sieve element occlusion (SEO) proteins (also known as forisomes), which are phloem proteins accumulated during sieve element differentiation [
,
]. This domain seems to be non-essential for dimerisation during forisome assembly [].
This entry represents the N terminus of the sieve element occlusion (SEO) proteins (also known as forisomes), which are phloem proteins accumulated during sieve element differentiation [
,
]. This domain mediates homologous dimerisation of the forisome protein MtSEO-F, probably via hydrophobic interplay [].
A number of nucleoside diphosphate and triphosphate hydrolases as well as some
yet uncharacterised proteins have been found to belong to the same family [,
]. The uncharacterised proteins all seem to be membrane-bound.
Mitochondrial phosphatidylglycerophosphatase (PGP phosphatase) (
) dephosphorylates phosphatidylglycerolphosphate to generate phosphatidylglycerol in cardiolipin biosynthesis. Cardiolipin is a unique dimeric phosphoglycerolipid predominantly present in mitochondrial membranes. The inverted phosphatase motif includes the highly conserved DKD triad [
,
]. In Saccharomyces cerevisiae, Gep4 is required for the stability of respiratory chain supercomplexes and for growth at elevated temperature, in presence of ethidium bromide or in absence of prohibitins []. Chloroplastic phosphatidylglycerophosphate phosphatase is involved in the biosynthesis of phosphatidylglycerol (PG), a phosphoglycerolipid present in chloroplastic thylakoid membranes and has a photosynthetic function [
].
This group of proteins is a part of the IIIA subfamily of the haloacid dehalogenase (HAD) superfamily of hydrolases. All characterised members of this subfamily and most characterised members of the HAD superfamily are phosphatases. HAD superfamily phosphatases contain active site residues in several conserved catalytic motifs [
], all of which are found conserved here.This family consists of sequences from fungi, plants, cyanobacteria, Gram-positive bacteria and Deinococcus. Proteins in this entry Includes phosphatidylglycerophosphatase Gep4 from budding yeasts and phosphatidylglycerophosphate phosphatase 1 (PGPP1) from plants. Gep4 is involved in the biosynthesis of cardiolipin and phosphatidylethanolamine for survival of prohibitin-deficient cells [
,
]. Chloroplastic PGPP1 is involved in the biosynthesis of phosphatidylglycerol (PG), a phosphoglycerolipid present in chloroplastic thylakoid membranes and has a photosynthetic function [].
This group of proteins is a part of the haloacid dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The Class III subfamilies are characterised by the lack of any domains located either between the first and second conserved catalytic motifs (as in the Class I subfamilies) or between the second and third conserved catalytic motifs (as in the Class II subfamilies) of the superfamily domain [
,
]. The IIIA subfamily contains five major clades: histidinol-phosphatase [], histidinol-phosphatase-related protein, DNA 3-phosphatase and sequences related to YqeG and YrbI.In the case of histidinol phosphatase and PNK-3'-phosphatase, this entry represents a domain of a bifunctional system. In the histidinol phosphatase HisB, a C-terminal domain is an imidazoleglycerol-phosphate dehydratase which catalyses a related step in histidine biosynthesis [
]. In PNK-3'-phosphatase, N- and C-terminal domains constitute the polynucleotide kinase and DNA-binding components of the enzyme.
CTP synthase is involved in pyrimidine ribonucleotide/ribonucleoside metabolism, catalysing the synthesis of CTP from UTP by amination of the pyrimidine ring at the 4-position [
]. The enzyme exists as a dimer which consists of an N-terminal synthetase domain and C-terminal glutaminase domain that aggregates as a tetramer. This gene has been found roughly 500 bp upstream of enolase in both beta (Nitrosomonas europaea) and gamma (Escherichia coli) subdivisions of Proteobacterium [].This entry represents the N-terminal synthetase domain of CTP synthase.
CTP synthase is involved in pyrimidine ribonucleotide/ribonucleoside metabolism, catalysing the synthesis of CTP from UTP by amination of the pyrimidine ring at the 4-position [
]. The enzyme exists as a dimer which consists of an N-terminal synthetase domain and C-terminal glutaminase domain that aggregates as a tetramer. This gene has been found roughly 500 bp upstream of enolase in both beta (Nitrosomonas europaea) and gamma (Escherichia coli) subdivisions of Proteobacterium [].
This entry represents the membrane-bound transcription factor site-2 protease (MBTPS2, also known as S2P) [
]. MBTPS2 is a membrane-embedded zinc metalloprotease that activates signaling proteins involved in sterol control of transcription and ER stress response [
]. It cleaves several transcription factors that are type-2 transmembrane proteins within membrane-spanning domains. Its known substrates include sterol regulatory element-binding protein (SREBP) -1, SREBP-2 and forms of the transcriptional activator ATF6 [,
]. Mutations in the MBTPS2 gene cause IFAP syndrome with or without BRESHECK syndrome (IFAPS) and Keratosis follicularis spinulosa decalvans X-linked (KFSDX) [
,
]. S2Ps are widely distributed in bacteria and participate in diverse pathways that control functions such as membrane integrity, sporulation, lipid biosynthesis, pheromone production, virulence, and others [
].
