| Type |
Details |
Score |
| Protein Domain |
| Name: |
RNA polymerase sigma factor RpoH, proteobacteria |
| Type: |
Family |
| Description: |
The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme [
]. RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors [
,
]. The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors [
].This entry represents the proteobacterial clade of sigma factors called RpoH. This protein may be called sigma-32, sigma factor H, heat shock sigma factor, and alternative sigma factor RpoH. Note that in some species the single locus rpoH may be replaced by two or more differentially regulated stress response sigma factors. |
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| Protein Domain |
| Name: |
Glutamine-tRNA ligase, bacterial |
| Type: |
Family |
| Description: |
This entry represents bacterial glutamine-tRNA ligases.Glutamine-tRNA ligase (
) is a class Ic aminoacyl-tRNA ligase and shows several similarities with glutamine-tRNA ligase concerning structure and catalytic properties. It is an alpha2 dimer.
Glutamine-tRNA ligase is a relatively rare ligase, found in the cytosolic compartment of eukaryotes, in Escherichia coli and a number of other Gram-negative bacteria, and in Deinococcus radiodurans. In contrast, the pathway to Gln-tRNA in mitochondria, Archaea, Gram-positive bacteria, and a number of other lineages is by misacylation with Glu followed by transamidation to correct the aminoacylation to Gln.The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [
]. |
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| Protein Domain |
| Name: |
HetR, N-terminal DNA-binding domain |
| Type: |
Homologous_superfamily |
| Description: |
HetR is a DNA-binding serine-type protease required for heterocyst differentiation in the nitrogen-fixing cyanobacteria under conditions of nitrogen deprivation. The protein binds to a DNA palindrome upstream of hetP and other genes. The HetR monomer is composed of three distinct domains: the N-terminal domain which is involved in DNA binding, the middle domain designated the "flap", and a slightly smaller C-terminal domain designated the "hood"[
]. HetR forms a dimer upon DNA binding. That structure contains four distinct domains: an extended DNA-binding unit containing helix-turn-helix (HTH) motifs comprised of two canonical α-helices in the DNA-binding domain and an auxiliary α-helix from the flap domain of the neighboring subunit; two histidine-rich flaps protruding on either side of the extended structure; and finally a hood comprised of the two C-terminal sequences [,
]. The whole HetR dimer becomes more symmetric in the presence of DNA. Overall, the flap orientations are adjusted to provide a more extended interaction with the twofold symmetric DNA duplex.This superfamily represents the DNA-binding domain, located at the N terminus, containing HTH motifs that penetrate the major groove of the DNA. This part of the HetR surface is positively charged. The DNA-binding unit should obey twofold symmetry, consistent with the palindromic nature of the HetR recognition sequence identified experimentally. The size of the DNA-binding unit suggests that the DNA target is approximately 16-17 bp long. A cavity between the two HTH motifs is clearly large enough to accommodate the minor groove and phosphate units of DNA. The positively charged patch extends beyond the HTH motifs into the flap domains, so the DNA target interacting with HetR may be longer. The HetR DNA-binding surface shows some curvature, suggesting that the bound DNA target might be bent. Additionally, three nests were found in the DNA-binding domain (S31G32H33, H68H69L70, and L11G12P13). These nests are in close proximity to each other and two of them are on the interface between the DNA-binding unit and the flap domain [
,
]. |
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| Protein Domain |
| Name: |
Alpha 2C adrenoceptor |
| Type: |
Family |
| Description: |
The adrenoceptors (or adrenergic receptors) are rhodopsin-like G protein-coupled receptors that are targets of the catecholamines, especially norepinephrine (noradrenaline) and epinephrine (adrenaline). Many cells possess these receptors, and the binding of a catecholamine to the receptor will generally stimulate the sympathetic nervous system, effect blood pressure, myocardial contractile rate and force, airway reactivity, and a variety of metabolic and central nervous system functions. The clinical uses of adrenergic compounds are vast. Agonists and antagonists interacting with adrenoceptors have proved useful in the treatment of a variety of diseases, including hypertension, angina pectoris, congestive heart failure, asthma, depression, benign prostatic hypertrophy, and glaucoma. These drugs are also useful in several other therapeutic situations including shock, premature labour and opioid withdrawal, and as adjuncts to general anaesthetics.There are three classes of adrenoceptors, based on their sequence similarity, receptor pharmacology and signalling mechanisms [
]. These three classes are alpha 1 (a Gq coupled receptor), alpha 2 (a Gi coupled receptor) and beta (a Gs coupled receptor), and each can be further divided into subtypes []. The different subtypes can coexist in some tissues, but one subtype normally predominates.There are three subtpyes of alpha 2 adrenoceptors (2A-C). The receptors are usually found presynaptically, where they inhibit the release of noradrenaline, and thus serve as an important receptor in the negative feedback control of noradrenaline release [
,
,
,
]. Postsynaptic alpha 2 receptors are located on liver cells, platelets, and the smooth muscle of blood vessels. Activation of the receptors causes platelet aggregation [], blood vessel constriction [,
] and constriction of vascular smooth muscle []. Agonists of alpha 2 adrenergic receptors are frequently used in veterinary anaesthesia, where they affect sedation, muscle relaxation and analgesia through their effects on the CNS []. Alpha 2 adrenoceptors are coupled through the Gi/Go mechanism, inhibiting adenylate cyclase activity and downregulating cAMP formation. This entry represents alpha 2C receptor, it is found mainly in the brain and kidney, and is absent in spleen, aorta, heart, liver, lung, skeletal muscle [
,
]. |
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| Protein Domain |
| Name: |
Alpha 2A adrenoceptor |
| Type: |
Family |
| Description: |
The adrenoceptors (or adrenergic receptors) are rhodopsin-like G protein-coupled receptors that are targets of the catecholamines, especially norepinephrine (noradrenaline) and epinephrine (adrenaline). Many cells possess these receptors, and the binding of a catecholamine to the receptor will generally stimulate the sympathetic nervous system, effect blood pressure, myocardial contractile rate and force, airway reactivity, and a variety of metabolic and central nervous system functions. The clinical uses of adrenergic compounds are vast. Agonists and antagonists interacting with adrenoceptors have proved useful in the treatment of a variety of diseases, including hypertension, angina pectoris, congestive heart failure, asthma, depression, benign prostatic hypertrophy, and glaucoma. These drugs are also useful in several other therapeutic situations including shock, premature labour and opioid withdrawal, and as adjuncts to general anaesthetics.There are three classes of adrenoceptors, based on their sequence similarity, receptor pharmacology and signalling mechanisms [
]. These three classes are alpha 1 (a Gq coupled receptor), alpha 2 (a Gi coupled receptor) and beta (a Gs coupled receptor), and each can be further divided into subtypes []. The different subtypes can coexist in some tissues, but one subtype normally predominates.There are three subtpyes of alpha 2 adrenoceptors (2A-C). The receptors are usually found presynaptically, where they inhibit the release of noradrenaline, and thus serve as an important receptor in the negative feedback control of noradrenaline release [
,
,
,
]. Postsynaptic alpha 2 receptors are located on liver cells, platelets, and the smooth muscle of blood vessels. Activation of the receptors causes platelet aggregation [], blood vessel constriction [,
] and constriction of vascular smooth muscle []. Agonists of alpha 2 adrenergic receptors are frequently used in veterinary anaesthesia, where they affect sedation, muscle relaxation and analgesia through their effects on the CNS []. Alpha 2 adrenoceptors are coupled through the Gi/Go mechanism, inhibiting adenylate cyclase activity and downregulating cAMP formation. This entry represents the alpha 2A adrenoceptor. It is expressed at high levels in the CNS, and in peripheral tissues such as kidney, aorta, skeletal muscle, spleen and lung [
,
,
,
]. |
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| Protein Domain |
| Name: |
RNA polymerase sigma-I type |
| Type: |
Family |
| Description: |
The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme [
]. RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors [
,
]. The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors [
].This entry represents the transcription factor Sigma-I. This protein is found in endospore-forming species in the Firmicutes lineage of bacteria, such as Bacillus subtilis, but is not universally present among such species. Sigma-I was shown to be induced by heat shock [
,
] in B. subtilis and is suggested by its phylogenetic profile to be connected to the program of sporulation []. |
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| Protein Domain |
| Name: |
Cobalt-precorrin-5B C(1)-methyltransferase CbiD |
| Type: |
Family |
| Description: |
CbiD is a SAM-dependent methyltransferase essential for cobalamin biosynthesis in both Salmonella typhimurium and Bacillus megaterium [
]. A deletion mutant of CbiD suggests that this enzyme is involved in C-1 methylation and deacylation reactions required during the ring contraction process in the anaerobic pathway to cobalamin (similar role as CobF) []. The CbiD protein has a putative S-AdoMet binding site []. CbiD has no counterpart in the aerobic pathway.Cobalamin (vitamin B12) is a structurally complex cofactor, consisting of a modified tetrapyrrole with a centrally chelated cobalt. Cobalamin is usually found in one of two biologically active forms: methylcobalamin and adocobalamin. Most prokaryotes, as well as animals, have cobalamin-dependent enzymes, whereas plants and fungi do not appear to use it. In bacteria and archaea, these include methionine synthase, ribonucleotide reductase, glutamate and methylmalonyl-CoA mutases, ethanolamine ammonia lyase, and diol dehydratase [
]. In mammals, cobalamin is obtained through the diet, and is required for methionine synthase and methylmalonyl-CoA mutase []. There are at least two distinct cobalamin biosynthetic pathways in bacteria [
]:Aerobic pathway that requires oxygen and in which cobalt is inserted late in the pathway [
]; found in Pseudomonas denitrificans and Rhodobacter capsulatus.Anaerobic pathway in which cobalt insertion is the first committed step towards cobalamin synthesis [
,
]; found in Salmonella typhimurium, Bacillus megaterium, and Propionibacterium freudenreichii subsp. shermanii. Either pathway can be divided into two parts: (1) corrin ring synthesis (differs in aerobic and anaerobic pathways) and (2) adenosylation of corrin ring, attachment of aminopropanol arm, and assembly of the nucleotide loop (common to both pathways) [
]. There are about 30 enzymes involved in either pathway, where those involved in the aerobic pathway are prefixed Cob and those of the anaerobic pathway Cbi. Several of these enzymes are pathway-specific: CbiD, CbiG, and CbiK are specific to the anaerobic route of S. typhimurium, whereas CobE, CobF, CobG, CobN, CobS, CobT, and CobW are unique to the aerobic pathway of P. denitrificans. |
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| Protein Domain |
| Name: |
PDGF/VEGF domain |
| Type: |
Domain |
| Description: |
Platelet-derived growth factor (PDGF) [
,
,
] is a potent mitogen for cells of mesenchymal origin, including smooth muscle cells and glial cells. In both mouse and human, the PDGF signalling network consists of four ligands, PDGFA-D, and two receptors, PDGFRalpha and PDGFRbeta. All PDGFs function as secreted, disulphide-linkedhomodimers, but only PDGFA and B can form functional heterodimers. PDGFRs also function as homo- and heterodimers. All known PDGFs have characteristic 'PDGF domains', which include eight conserved cysteines that are involved in inter- and intramolecular bonds. Alternate splicing of the A chain transcript can give rise to two different forms that differ only in their C-terminal extremity. The transforming protein of Woolly monkey sarcoma virus (WMSV) (Simian sarcoma virus), encoded by the v-sis oncogene, is derived from the B chain of PDGF.
PDGFs are mitogenic during early developmental stages, driving the proliferation of undifferentiated mesenchyme and some progenitor populations. During later maturation stages, PDGF signalling has been implicated in tissue remodelling and cellular differentiation, and in inductive events involved in patterning and morphogenesis. In addition to driving mesenchymal proliferation, PDGFs have been shown to direct the migration, differentiation and function of a variety of specialised mesenchymal and migratory cell types, both during development and in the adult animal [
].Other growth factors in this family include vascular endothelial growth factors B and C (VEGF-B, VEGF-C) [
,
] which are active in angiogenesis and endothelial cell growth, and placenta growth factor (PlGF) which is also active in angiogenesis [
]. VEGF is a potent mitogen in embryonic and somatic angiogenesis with a unique specificity for vascular endothelial cells. VEGF forms homodimers and exists in 4 different isoforms. Overall, the VEGF monomer resembles that of PDGF, but its N-terminal segment is helical rather than extended.PDGF is structurally related to a number of other growth factors which also form disulphide-linked homo- or heterodimers. A cysteine knot motif is a common feature of this domain [
,
,
]. |
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| Protein Domain |
| Name: |
CbiD superfamily |
| Type: |
Homologous_superfamily |
| Description: |
CbiD is a SAM-dependent methyltransferase essential for cobalamin biosynthesis in both Salmonella typhimurium and Bacillus megaterium [
]. A deletion mutant of CbiD suggests that this enzyme is involved in C-1 methylation and deacylation reactions required during the ring contraction process in the anaerobic pathway to cobalamin (similar role as CobF) []. The CbiD protein has a putative S-AdoMet binding site []. CbiD has no counterpart in the aerobic pathway.Cobalamin (vitamin B12) is a structurally complex cofactor, consisting of a modified tetrapyrrole with a centrally chelated cobalt. Cobalamin is usually found in one of two biologically active forms: methylcobalamin and adocobalamin. Most prokaryotes, as well as animals, have cobalamin-dependent enzymes, whereas plants and fungi do not appear to use it. In bacteria and archaea, these include methionine synthase, ribonucleotide reductase, glutamate and methylmalonyl-CoA mutases, ethanolamine ammonia lyase, and diol dehydratase [
]. In mammals, cobalamin is obtained through the diet, and is required for methionine synthase and methylmalonyl-CoA mutase []. There are at least two distinct cobalamin biosynthetic pathways in bacteria [
]:Aerobic pathway that requires oxygen and in which cobalt is inserted late in the pathway [
]; found in Pseudomonas denitrificans and Rhodobacter capsulatus.Anaerobic pathway in which cobalt insertion is the first committed step towards cobalamin synthesis [
,
]; found in Salmonella typhimurium, Bacillus megaterium, and Propionibacterium freudenreichii subsp. shermanii. Either pathway can be divided into two parts: (1) corrin ring synthesis (differs in aerobic and anaerobic pathways) and (2) adenosylation of corrin ring, attachment of aminopropanol arm, and assembly of the nucleotide loop (common to both pathways) [
]. There are about 30 enzymes involved in either pathway, where those involved in the aerobic pathway are prefixed Cob and those of the anaerobic pathway Cbi. Several of these enzymes are pathway-specific: CbiD, CbiG, and CbiK are specific to the anaerobic route of S. typhimurium, whereas CobE, CobF, CobG, CobN, CobS, CobT, and CobW are unique to the aerobic pathway of P. denitrificans. |
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| Protein Domain |
| Name: |
Copper amine oxidase-like, N-terminal domain superfamily |
| Type: |
Homologous_superfamily |
| Description: |
Amine oxidases (AO) are enzymes that catalyse the oxidation of a wide range of biogenic amines including many neurotransmitters, histamine and xenobiotic amines. There are two classes of amine oxidases: flavin-containing (
) and copper-containing (
). Copper-containing AO act as a disulphide-linked homodimer. They catalyse the oxidation of primary amines to aldehydes, with the subsequent release of ammonia and hydrogen peroxide, which requires one copper ion per subunit and topaquinone as cofactor [
]: RCH
2NH
2+ H
2O + O
2= RCHO + NH
3+ H
2O
2Copper-containing amine oxidases are found in bacteria, fungi, plants and animals. In prokaryotes, the enzyme enables various amine substrates to be used as sources of carbon and nitrogen [
,
]. In eukaryotes they have a broader range of functions, including cell differentiation and growth, wound healing, detoxification and cell signalling [].The copper amine oxidases occur as mushroom-shaped homodimers of 70-95kDa, each monomer containing a copper ion and a covalently bound redox cofactor, topaquinone (TPQ). TPQ is formed by post-translational modification of a conserved tyrosine residue. The copper ion is coordinated with three histidine residues and two water molecules in a distorted square pyramidal geometry, and has a dual function in catalysis and TPQ biogenesis. The catalytic domain is the largest of the 3-4 domains found in copper amine oxidases, and consists of a beta sandwich of 18 strands in two sheets. The active site is buried and requires a conformational change to allow the substrate access. The two N-terminal domains share a common structural fold, its core consisting of a five-stranded antiparallel β-sheet twisted around an α-helix. The D1 domains from the two subunits comprise the stalk, of the mushroom-shaped dimer, and interact with each other but do not pack tightly against each other [,
]. This entry represents a domain superfamily found at the N-terminal of certain copper amine oxidases, as well as in related proteins such as cell wall hydrolase and N-acetylmuramoyl-L-alanine amidase. This domain consists of a five-stranded antiparallel β-sheet twisted around an alpha helix [
,
]. |
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| Protein Domain |
| Name: |
Ryanodine/Inositol 1,4,5-trisphosphate receptor |
| Type: |
Family |
| Description: |
The ryanodine and inositol 1,4,5-triphosphate (IP3) receptors are intracellular Ca2+ release channels characterised by their large size and 4-fold symmetry [
]. In excitation-contraction coupling of skeletal and heart muscle, the ryanodine receptor serves as a Ca2+ release channel of sarcoplasmic reticulum (SR) and is morphologically identical to the foot structure spanning the gap between terminal cisternae of SR and sarcolemma/transverse tubules. The IP3 receptor acts as a Ca2+ release channel of non-mitochondrial intracellular Ca2+ stores in smooth muscle and in non-muscle tissues.The so-called excitation-contraction coupling phenomenon in muscle cells takes place in a highly specialised junctional region that arise from close proximity between plasma membrane (PM) and SR. More precisely, transverse tubular invaginations of the PM touch the terminal cisternae of SR to form a unique anatomical structure known as the triad junction [
,
,
]. In skeletal muscle, dihydropyridine receptors (DHPRs) located in the transverse tubule membrane function mainly as the voltage sensor which sends an orthograde signal to control opening of the ryanodine receptor/Ca2+ release channel [,
]. There appears to a physical interaction between DHPRs and ryanodine receptors in the triad junction without requiring the movement of extracellular Ca2+ through DHPRs in the PM [].IP3 receptors are large (~1200kDa) tetrameric proteins, each subunit of which projects an amino-terminal domain into the cytoplasm, their membrane-spanning carboxy-terminal regions forming an integral Ca2+ channel. IP3 binding by the amino-terminal domains causes a conformational change that promotes channel opening. Between the IP3 binding site and the transmembrane regions is a large stretch of amino acids where a significant proportion of regulatory interactions occur. Although IP3 is necessary to open native IP3 receptors, activation of these channels is complex and their open probability actually depends on the ambient Ca2+ concentration. Up to ~ 500 nM, Ca2+ works synergistically with IP3 to activate IP3 receptors. At higher concentrations, cytosolic Ca2+ inhibits IP3 receptor opening. The inhibition of IP3 receptors by Ca2+ is thought to be a crucial mechanism for terminating channel activity and thus preventing pathological Ca2+ rises. |
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| Protein Domain |
| Name: |
Pepsin-like domain, plant |
| Type: |
Domain |
| Description: |
This entry represents a domain found in aspartic endopeptidases from plants including nepenthesin (MEROPS identifier A01.040), a digestive enzyme from the pitcher of the carnivorous pitcher plant Nepenthes [
]; CDR1 endopeptidase (=Constitutive Disease Resistance 1; MEROPS identifier A01.069) from the Arabidopsis apoplast involved in disease resistance signalling and which is notinhibited by pepstatin [
]; PCS1 peptidase (MEROPS identifier A01.074) which is important for protecting cells from apoptosis during embryo development []; and S5 peptidases (MEROPS identifier A01.086), which exist as homo- and hetero- dimers and formation of heterodimers leads to embryo-sac abortion resulting in sterility []. Proteins containing this domain belong to the aspartic peptidase A1 family (peptidase family A1, subfamily A1B).Aspartyl proteases (APs), also known as acid proteases, ([intenz:3.4.23.-]) are a widely distributed family of proteolytic enzymes [,
,
,
,
,
] known to exist in vertebrates, fungi, plants, retroviruses and some plant viruses. APs use an Asp dyad to hydrolyze peptide bonds.APs found in eukaryotic cells are α/β monomers composed of two asymmetric lobes ("bilobed"). Each of the lobes provides a catalytic Asp residue, positioned within the hallmark motif Asp-Thr/Ser-Gly, to the active site. The N- and C-terminal domains, although structurally related by a 2-fold axis, have only limited sequence homology except the vicinity of the active site. This suggests that the enzymes evolved by an ancient duplication event. The enzymes specifically cleave bonds in peptides which have at least six residues in length with hydrophobic residues in both the P1 and P1' positions. The active site is located at the groove formed by the two lobes, with an extended loop projecting over the cleft to form an 11-residue flap, which encloses substrates and inhibitors in the active site. Specificity is determined by nearest-neighbour hydrophobic residues surrounding the catalytic aspartates, and by three residues in the flap. The enzymes are mostly secreted from cells as inactive proenzymes that activate autocatalytically at acidic pH. Eukaryotic APs form peptidase family A1 of clan AA. |
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| Protein Domain |
| Name: |
Aspergillopepsin-like catalytic domain |
| Type: |
Domain |
| Description: |
This entry represents the peptidase domain found in a group of aspartic endopeptidases of fungal origin, including aspergillopepsin (MEROPS ientifier A01.016) [
], rhizopuspepsin (A01.012), endothiapepsin (A01.017) and penicillopepsin (A01.011) []. Aspergillopepsin from A. fumigatus is involved in invasive aspergillosis owing to its elastolytic activity [] and aspergillopepsins from the mold A. saitoi are used in the fermentation industry []. The members in this entry have an optimal acidic pH (5.5) and cleave protein substrates with similar specificity to that of porcine pepsin A, preferring hydrophobic residues at P1 and P1' in the cleavage site. This group of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA) [].Aspartyl proteases (APs), also known as acid proteases, ([intenz:3.4.23.-]) are a widely distributed family of proteolytic enzymes [,
,
,
,
,
] known to exist in vertebrates, fungi, plants, retroviruses and some plant viruses. APs use an Asp dyad to hydrolyze peptide bonds.APs found in eukaryotic cells are α/β monomers composed of two asymmetric lobes ("bilobed"). Each of the lobes provides a catalytic Asp residue, positioned within the hallmark motif Asp-Thr/Ser-Gly, to the active site. The N- and C-terminal domains, although structurally related by a 2-fold axis, have only limited sequence homology except the vicinity of the active site. This suggests that the enzymes evolved by an ancient duplication event. The enzymes specifically cleave bonds in peptides which have at least six residues in length with hydrophobic residues in both the P1 and P1' positions. The active site is located at the groove formed by the two lobes, with an extended loop projecting over the cleft to form an 11-residue flap, which encloses substrates and inhibitors in the active site. Specificity is determined by nearest-neighbour hydrophobic residues surrounding the catalytic aspartates, and by three residues in the flap. The enzymes are mostly secreted from cells as inactive proenzymes that activate autocatalytically at acidic pH. Eukaryotic APs form peptidase family A1 of clan AA. |
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| Protein Domain |
| Name: |
Carboxypeptidase E, carboxypeptidase domain |
| Type: |
Domain |
| Description: |
This entry represents the carboxypeptidase domain found in carboxypeptidase (CP) E (CPE, also known as carboxypeptidase H, and enkephalin convertase;(
); MEROPS identifier M14.005). CPE belongs to subfamily M14B (N/E subfamily) of the M14 family of metallocarboxypeptidases (MCPs) [
]. It is an important enzyme responsible for the proteolytic processing of prohormone intermediates (such as pro-insulin, pro-opiomelanocortin, or pro-gonadotropin-releasing hormone) by specifically removing C-terminal basic residues []. In addition, it has been proposed that the regulated secretory pathway (RSP) of the nervous and endocrine systems utilizes membrane-bound CPE as a sorting receptor. A naturally occurring point mutation in CPE reduces the stability of the enzyme and causes its degradation, leading to an accumulation of numerous neuroendocrine peptides that result in obesity and hyperglycemia [,
]. Reduced CPE enzyme and receptor activity could underlie abnormal placental phenotypes from the observation that CPE is down-regulated in enlarged placentas of interspecific hybrid (interspecies hybrid placental dysplasia, IHPD) and cloned mice [].The carboxypeptidase A family can be divided into four subfamilies: M14A
(carboxypeptidase A or digestive), M14B (carboxypeptidase H or regulatory), M14C (gamma-D-glutamyl-L-diamino acid peptidase I) and M14D (AGTPBP-1/Nna1-like proteins) [,
]. Members of subfamily M14B have longer C-termini than those of subfamily M14A [], and carboxypeptidase M (a member of the H family) is bound to the membrane by a glycosylphosphatidylinositol anchor, unlike the majority of the M14 family, which are soluble [
]. The zinc ligands have been determined as two histidines and a glutamate,and the catalytic residue has been identified as a C-terminal glutamate,
but these do not form the characteristic metalloprotease HEXXH motif [,
]. Members of the carboxypeptidase A family are synthesised as inactive molecules with propeptides that must be cleaved to activate the enzyme. Structural studies of carboxypeptidases A and B reveal the propeptide to exist as a globular domain, followed by an extended α-helix; this shields the catalytic site, without specifically binding to it, while the substrate-binding site is blocked by making specific contacts [,
]. |
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| Protein Domain |
| Name: |
RNA polymerase sigma factor 70, ECF, conserved site |
| Type: |
Conserved_site |
| Description: |
The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme [
]. RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors [
,
]. The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors [
].The proteins in this entry are currently known to belong to this sigma factor subfamily, known as ECF; these include Pseudomonas aeruginosa algU; Myxococcus xanthus carQ; Ralstonia eutropha (Alcaligenes eutrophus) plasmid pMOL28-encoded cnrH; Escherichia coli fecI; Pseudomonas syringae hrpL; rpoE from E. coli, Salmonella typhimurium and Haemophilus influenzae; Streptomyces coelicolor sigE; and Bacillus subtilis sigma factors sigV, sigX, sigY and sigZ. |
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| Protein Domain |
| Name: |
Copper amine oxidase-like, N-terminal |
| Type: |
Domain |
| Description: |
Amine oxidases (AO) are enzymes that catalyse the oxidation of a wide range of biogenic amines including many neurotransmitters, histamine and xenobiotic amines. There are two classes of amine oxidases: flavin-containing (
) and copper-containing (
). Copper-containing AO act as a disulphide-linked homodimer. They catalyse the oxidation of primary amines to aldehydes, with the subsequent release of ammonia and hydrogen peroxide, which requires one copper ion per subunit and topaquinone as cofactor [
]: RCH
2NH
2+ H
2O + O
2= RCHO + NH
3+ H
2O
2Copper-containing amine oxidases are found in bacteria, fungi, plants and animals. In prokaryotes, the enzyme enables various amine substrates to be used as sources of carbon and nitrogen [
,
]. In eukaryotes they have a broader range of functions, including cell differentiation and growth, wound healing, detoxification and cell signalling [].The copper amine oxidases occur as mushroom-shaped homodimers of 70-95kDa, each monomer containing a copper ion and a covalently bound redox cofactor, topaquinone (TPQ). TPQ is formed by post-translational modification of a conserved tyrosine residue. The copper ion is coordinated with three histidine residues and two water molecules in a distorted square pyramidal geometry, and has a dual function in catalysis and TPQ biogenesis. The catalytic domain is the largest of the 3-4 domains found in copper amine oxidases, and consists of a beta sandwich of 18 strands in two sheets. The active site is buried and requires a conformational change to allow the substrate access. The two N-terminal domains share a common structural fold, its core consisting of a five-stranded antiparallel β-sheet twisted around an α-helix. The D1 domains from the two subunits comprise the stalk, of the mushroom-shaped dimer, and interact with each other but do not pack tightly against each other [
,
]. This entry represents a domain found at the N-terminal of certain copper amine oxidases, as well as in related proteins such as cell wall hydrolase and N-acetylmuramoyl-L-alanine amidase. This domain consists of a five-stranded antiparallel β-sheet twisted around an alpha helix [
,
]. |
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| Protein Domain |
| Name: |
Pancreatic hormone-like, conserved site |
| Type: |
Conserved_site |
| Description: |
Pancreatic hormone (PP) [
] is a peptide synthesized in pancreatic islets of Langherhans, which acts as a regulator of pancreatic and gastrointestinal functions.The hormone is produced as a larger propeptide, which is enzymatically cleaved to yield the mature active peptide: this is 36 amino acids in length [
] and has an amidated C terminus []. The hormone has a globular structure, residues 2-8 forming a left-handed poly-proline-II-like helix, residues 9-13 a beta turn, and 14-32 an α-helix, held close to the first helix by hydrophobic interactions []. Unlike glucagon, another peptide hormone, the structure of pancreatic peptide is preserved in aqueous solution []. Both N and C termini are required for activity: receptor binding and activation functions may reside in the N and C termini respectively [].Pancreatic hormone is part of a wider family of active peptides that includes:Neuropeptide Y (NPY or melanostatin) [
], one of the most abundant peptides in the mammalian nervous system. NPY is implicated in the control of feeding and the secretion of the gonadotropin-releasing hormone.Peptide YY (PYY) [
]. PPY is a gut peptide that inhibits exocrine pancreatic secretion, has a vasoconstrictor action and inhibits jejunal and colonic mobility. Known as goannatyrotoxin-Vere1 in the venom of the pygmy desert monitor lizard (Varanus eremius) where it has a triphasic action: rapid biphasic hypertension followed by prolonged hypotension in prey animals [
].Various NPY and PYY-like polypeptides from fish and amphibians [
,
].Neuropeptide F (NPF) from invertebrates such as worms and snail.Skin peptide Tyr-Tyr (SPYY) from the frog Phyllomedusa bicolor. SPYY shows a large spectra of antibacterial and antifungal activity.Polypeptide MY (peptide methionine-tyrosine). A regulatory peptide from the intestine of the sea lamprey (Petromyzon marinus) [
].All these peptides are 36 to 39 amino acids long. Like most active peptides, their C-terminal is amidated and they are synthesized as larger protein precursors.This entry represents a conserved region corresponding to the C-terminal end of the active peptide. |
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| Protein Domain |
| Name: |
P2X2 purinoceptor |
| Type: |
Family |
| Description: |
P2X purinoceptors are cell membrane ion channels, gated by adenosine 5'-triphosphate (ATP) and other nucleotides; they have been found to be widely expressed on mammalian cells, and, by means of their functional properties, can be differentiated into three sub-groups. The first group is almost equally well activated by ATP and its analogue alpha,betamethylene-ATP, whereas, the second group is not activated by the latter compound. A third type of receptor (also called P2Z) is distinguished by the fact that repeated or prolonged agonist application leads to the opening of much larger pores, allowing large molecules to traverse the cell membrane. This increased permeability rapidly leads to cell death, and lysis.Molecular cloning studies have identified seven P2X receptor subtypes, designated P2XR1-P2XR7, however, P2X1R, P2X2R, P2X3R, P2X4R, and P2X7R are functional [
]. These receptors are proteins that share 35-48% amino acid identity, and possess two putative transmembrane (TM) domains, separated by a long (~270 residues) intervening sequence, which is thought to form an extracellular loop. Around 1/4 of the residues within the loop are invariant between the cloned subtypes, including 10 characteristic cysteines.Studies of the functional properties of heterologously expressed P2X receptors, together with the examination of their distribution in native tissues, suggests they likely occur as both homo- and hetero multimers in vivo [
,
]. Stimulation of these receptors induces changes in intracellular ion homeostasis leading to multiple key responses crucial for initiation, propagation, and resolution of inflammation []. The P2X7 subtype has an important role in the activation of lymphocyte, granulocyte, macrophage and dendritic cell responses and, therefor, it may be a promising target for anti-inflammatory therapies.P2X2 receptors (which have been found to be alternatively spliced), are
half-maximally activated by a concentration of ATP of ~10 micromolar. In contrast, alphabetamethyleneATP is found to be largely ineffective. This
agonist profile has been found to be shared by the P2X4, P2X5 and P2X6receptors. The single-channel properties of the P2X2 receptor are quite
similar to those noted for the native receptor present on PC12 cells []. |
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| Protein Domain |
| Name: |
P2X4 purinoceptor |
| Type: |
Family |
| Description: |
P2X purinoceptors are cell membrane ion channels, gated by adenosine 5'-triphosphate (ATP) and other nucleotides; they have been found to be widely expressed on mammalian cells, and, by means of their functional properties, can be differentiated into three sub-groups. The first group is almost equally well activated by ATP and its analogue alpha,betamethylene-ATP, whereas, the second group is not activated by the latter compound. A third type of receptor (also called P2Z) is distinguished by the fact that repeated or prolonged agonist application leads to the opening of much larger pores, allowing large molecules to traverse the cell membrane. This increased permeability rapidly leads to cell death, and lysis.Molecular cloning studies have identified seven P2X receptor subtypes, designated P2XR1-P2XR7, however, P2X1R, P2X2R, P2X3R, P2X4R, and P2X7R are functional [
]. These receptors are proteins that share 35-48% amino acid identity, and possess two putative transmembrane (TM) domains, separated by a long (~270 residues) intervening sequence, which is thought to form an extracellular loop. Around 1/4 of the residues within the loop are invariant between the cloned subtypes, including 10 characteristic cysteines.Studies of the functional properties of heterologously expressed P2X receptors, together with the examination of their distribution in native tissues, suggests they likely occur as both homo- and hetero multimers in vivo [
,
]. Stimulation of these receptors induces changes in intracellular ion homeostasis leading to multiple key responses crucial for initiation, propagation, and resolution of inflammation []. The P2X7 subtype has an important role in the activation of lymphocyte, granulocyte, macrophage and dendritic cell responses and, therefor, it may be a promising target for anti-inflammatory therapies.The P2X4 receptor (along with P2X2, P2X5 and P2X6) falls into a group of receptors that are sensitive to ATP, but not alphabetamethyleneATP. There is some evidence that P2X4 may heteropolymerise with P2X6, since they are often found together in native tissues, and can be co-immunoprecipitated. Splice variants of the P2X4 receptor have been detected [
]. |
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| Protein Domain |
| Name: |
Peroxisome proliferator-activated receptor alpha |
| Type: |
Family |
| Description: |
Peroxisome proliferator-activated receptors (PPAR) are ligand-activated
transcription factors that belong to the nuclear hormone receptor superfamily. Three subtypes of this receptor have been discovered: PPAR alpha, beta and gamma [
]. They control a variety of target genes involved in lipid homeostasis, diabetes and cancer []. PPAR-alpha is a regulator of lipid metabolism [
]. It modulates the activities of all three fatty acid oxidation systems, namely mitochondrial and peroxisomal beta-oxidation and microsomal omega-oxidation []. Oleoylethanolamide (OEA), a naturally occurring lipid that regulates feeding and body weight, has been shown to bind with high affinity to PPAR-alpha []. Steroid or nuclear hormone receptors (NRs) constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis. Members of the superfamily include the steroid hormone receptors and receptors for thyroid hormone, retinoids, 1,25-dihydroxy-vitamin D3 and a variety of other ligands [
]. The proteins function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner [,
]. In addition to C-terminal ligand-binding domains, these nuclear receptors contain a highly-conserved, N-terminal zinc-finger that mediates specific binding to target DNA sequences, termed ligand-responsive elements. In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity.NRs are extremely important in medical research, a large number of them being implicated in diseases such as cancer, diabetes, hormone resistance syndromes, etc. While several NRs act as ligand-inducible transcription factors, many do not yet have a defined ligand and are accordingly termed 'orphan' receptors. During the last decade, more than 300 NRs have been described, many of which are orphans, which cannot easily be named due to current nomenclature confusions in the literature. However, a new system has recently been introduced in an attempt to rationalise the increasingly complex set of names used to describe superfamily members. |
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| Protein Domain |
| Name: |
P2X7 purinoceptor |
| Type: |
Family |
| Description: |
P2X purinoceptors are cell membrane ion channels, gated by adenosine 5'-triphosphate (ATP) and other nucleotides; they have been found to be widely expressed on mammalian cells, and, by means of their functional properties, can be differentiated into three sub-groups. The first group is almost equally well activated by ATP and its analogue alpha,betamethylene-ATP, whereas, the second group is not activated by the latter compound. A third type of receptor (also called P2Z) is distinguished by the fact that repeated or prolonged agonist application leads to the opening of much larger pores, allowing large molecules to traverse the cell membrane. This increased permeability rapidly leads to cell death, and lysis.Molecular cloning studies have identified seven P2X receptor subtypes, designated P2XR1-P2XR7, however, P2X1R, P2X2R, P2X3R, P2X4R, and P2X7R are functional [
]. These receptors are proteins that share 35-48% amino acid identity, and possess two putative transmembrane (TM) domains, separated by a long (~270 residues) intervening sequence, which is thought to form an extracellular loop. Around 1/4 of the residues within the loop are invariant between the cloned subtypes, including 10 characteristic cysteines.Studies of the functional properties of heterologously expressed P2X receptors, together with the examination of their distribution in native tissues, suggests they likely occur as both homo- and hetero multimers in vivo [,
]. Stimulation of these receptors induces changes in intracellular ion homeostasis leading to multiple key responses crucial for initiation, propagation, and resolution of inflammation []. The P2X7 subtype has an important role in the activation of lymphocyte, granulocyte, macrophage and dendritic cell responses and, therefor, it may be a promising target for anti-inflammatory therapies.This entry represents P2X7 (also known as P2Z receptor), which, when P2X7 receptor is expressed, it is found to have different functional properties from those of P2X1-P2X6. Key properties of the current produced are little rectification or desensitisation, and strong potentiation of responses when the concentration of extracellular Ca2+ and/or Mg2+ are reduced. It is also found to be relatively insensitive to ATP. In certain studies, prolonged activation of expressed P2X7 receptors causes cell permeabilization, and lysis. |
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| Protein Domain |
| Name: |
Glutaminyl-tRNA synthetase, class Ib, non-specific RNA-binding domain, N-terminal, subdomain 1 |
| Type: |
Homologous_superfamily |
| Description: |
The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [].The N-terminal appended domain (NTD) of glutaminyl-tRNA synthetase consists consists of two alpha helical domains, the first from containing a seven-helix bundle, and the second containing a four-helix bundle, which are connected by a seven residue linker [
]. It is thought to bind RNA in a non-specific manner, enhancing interactions between the tRNA and enzyme, but is not essential for enzyme function [].This superfamily represents the subdomain 1 found at the N-terminal of glutaminyl-tRNA synthetase (
) in eukaryotes but not in Escherichia coli.
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| Protein Domain |
| Name: |
Glutaminyl-tRNA synthetase, class Ib, non-specific RNA-binding domain, N-terminal, subdomain 2 |
| Type: |
Homologous_superfamily |
| Description: |
The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classesof tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [
].The N-terminal appended domain (NTD) of glutaminyl-tRNA synthetase consists consists of two alpha helical domains, the first from containing a seven-helix bundle, and the second containing a four-helix bundle, which are connected by a seven residue linker [
]. It is thought to bind RNA in a non-specific manner, enhancing interactions between the tRNA and enzyme, but is not essential for enzyme function [].This superfamily represents the subdomain 2 found at the N-terminal of glutaminyl-tRNA synthetase (
) in eukaryotes but not in Escherichia coli.
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| Protein Domain |
| Name: |
Nitrile hydratase, beta subunit |
| Type: |
Family |
| Description: |
Nitrile hydratases (
) are bacterial enzymes that catalyse the hydration of nitrile compounds to the corresponding amides. They are used as biocatalysts in acrylamide production, one of the few commercial scale bioprocesses, as well as in environmental remediation for the removal of nitriles from waste streams. Nitrile hydratases are composed of two subunits, alpha and beta, and are normally active as a tetramer, alpha(2)beta(2). Nitrile hydratases contain either a non-haem iron or a non-corrinoid cobalt centre, both types sharing a highly conserved peptide sequence in the alpha subunit (CXLCSC) that provides all the residues involved in coordinating the metal ion. Each type of nitrile hydratase specifically incorporated its metal with the help of activator proteins encoded by flanking regions of the nitrile hydratase genes that are necessary for metal insertion. The Fe-containing enzyme is photo-regulated: in the dark the enzyme is inactivated due to the association of nitric oxide (NO) to the iron, while in the light the enzyme is active by photo-dissociation of NO. The NO is held in place by a claw setting formed through specific oxygen atoms in two modified cysteines and a serine residue in the active site [
,
]. The cobalt-containing enzyme is unaffected by NO, but was shown to undergo a similar effect with carbon monoxide [,
]. Fe- and cobalt-containing enzymes also display different inhibition patterns with nitrophenols.Thiocyanate hydrolase (SCNase) is a cobalt-containing metalloenzyme with a cysteine-sulphinic acid ligand that hydrolyses thiocyanate to carbonyl sulphide and ammonia [
].The two enzymes, nitrile hydratase and SCNase, are homologous over regions corresponding to almost the entire coding regions of the genes: the beta and alpha subunits of thiocyanate hydrolase were homologous to the amino- and carboxyl-terminal halves of the beta subunit of nitrile hydratase, and the gamma subunit of thiocyanate hydrolase was homologous to the alpha subunit of nitrile hydratase [
].This entry represents the beta subunit. |
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| Protein Domain |
| Name: |
Moybdenum cofactor oxidoreductase, dimerisation |
| Type: |
Domain |
| Description: |
The majority of molybdenum-containing enzymes utilise a molybdenum cofactor (MoCF or Moco) consisting of a Mo atom coordinated via a cis-dithiolene moiety to molybdopterin (MPT). MoCF is ubiquitous in nature, and the pathway for MoCF biosynthesis is conserved in all three domains of life. MoCF-containing enzymes function as oxidoreductases in carbon, nitrogen, and sulphur metabolism [
,
]. In Escherichia coli, biosynthesis of MoCF is a three stage process. It begins with the MoaA and MoaC conversion of GTP to the meta-stable pterin intermediate precursor Z. The second stage involves MPT synthase (MoaD and MoaE), which converts precursor Z to MPT; MoeB is involved in the recycling of MPT synthase. The final step in MoCF synthesis is the attachment of mononuclear Mo to MPT, a process that requires MoeA and which is enhanced by MogA in an Mg2 ATP-dependent manner [
]. MoCF is the active co-factor in eukaryotic and some prokaryotic molybdo-enzymes, but the majority of bacterial enzymes requiring MoCF, need a modification of MTP for it to be active; MobA is involved in the attachment of a nucleotide monophosphate to MPT resulting in the MGD co-factor, the active co-factor for most prokaryotic molybdo-enzymes. Bacterial two-hybrid studies have revealed the close interactions between MoeA, MogA, and MobA in the synthesis of MoCF []. Moreover the close functional association of MoeA and MogA in the synthesis of MoCF is supported by fact that the known eukaryotic homologues to MoeA and MogA exist as fusion proteins: CNX1 () of Arabidopsis thaliana (Mouse-ear cress), mammalian Gephryin (e.g.
) and Drosophila melanogaster (Fruit fly) Cinnamon (
) [
].This domain is found in molybdopterin cofactor oxidoreductases, such as in the C-terminal of Mo-containing sulphite oxidase, which catalyses the conversion of sulphite to sulphate, the terminal step in the oxidative degradation of cysteine and methionine [
]. This domain is involved in dimer formation, and has an Ig-fold structure []. |
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| Protein Domain |
| Name: |
DNA ligase, ATP-dependent, central |
| Type: |
Domain |
| Description: |
DNA ligase (polydeoxyribonucleotide synthase) is the enzyme that joins two DNA fragments by catalysing the formation of an internucleotide ester bond between phosphate and deoxyribose. It is active during DNA replication, DNA repair and DNA recombination. There are two forms of DNA ligase, one requires ATP (
), the other NAD (
), the latter being restricted to eubacteria. Eukaryotic, archaebacterial, viral and some eubacterial DNA ligases are ATP-dependent. The first step in the ligation reaction is the formation of a covalent enzyme-AMP complex. The co-factor ATP is cleaved to pyrophosphate and AMP, with the AMP being covalently joined to a highly conserved lysine residue in the active site of the ligase. The activated AMP residue is then transferred to the 5'phosphate of the nick, before the nick is sealed by phosphodiester-bond formation and AMP elimination [
,
].Vertebrate cells encode three well-characterised DNA ligases (DNA ligases I, III and IV), all of which are related in structure and sequence. With the exception of the atypically small PBCV-1 viral enzyme, two regions of primary sequence are common to all members of the family. The catalytic region comprises six conserved sequence motifs (I, III, IIIa, IV, V-VI), motif I includes the lysine residue that is adenylated in the first step of the ligation reaction. The function of the second, less well-conserved region is unknown. When folded, each protein comprises of two distinct sub-domains: a large amino-terminal sub-domain ('domain 1') and a smaller carboxy-terminal sub-domain ('domain 2'). The ATP-binding site of the enzyme lies in the cleft between the two sub-domains. Domain 1 consists of two antiparallel beta sheets flanked by alpha helices, whereas domain 2 consists of a five-stranded beta barrel and a single alpha helix, which form the oligonucleotide-binding fold [
,
]. This domain belongs to a more diverse superfamily, including catalytic domain of the mRNA capping enzyme (
) and NAD-dependent DNA ligase (
) [
]. |
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| Protein Domain |
| Name: |
DNA ligase, ATP-dependent, C-terminal |
| Type: |
Domain |
| Description: |
DNA ligase (polydeoxyribonucleotide synthase) is the enzyme that joins two DNA fragments by catalysing the formation of an internucleotide ester bond between phosphate and deoxyribose. It is active during DNA replication, DNA repair and DNA recombination. There are two forms of DNA ligase, one requires ATP (
), the other NAD (
), the latter being restricted to eubacteria. Eukaryotic, archaebacterial, viral and some eubacterial DNA ligases are ATP-dependent. The first step in the ligation reaction is the formation of a covalent enzyme-AMP complex. The co-factor ATP is cleaved to pyrophosphate and AMP, with the AMP being covalently joined to a highly conserved lysine residue in the active site of the ligase. The activated AMP residue is then transferred to the 5'phosphate of the nick, before the nick is sealed by phosphodiester-bond formation and AMP elimination [
,
].Vertebrate cells encode three well-characterised DNA ligases (DNA ligases I, III and IV), all of which are related in structure and sequence. With the exception of the atypically small PBCV-1 viral enzyme, two regions of primary sequence are common to all members of the family. The catalytic region comprises six conserved sequence motifs (I, III, IIIa, IV, V-VI), motif I includes the lysine residue that is adenylated in the first step of the ligation reaction. The function of the second, less well-conserved region is unknown. When folded, each protein comprises of two distinct sub-domains: a large amino-terminal sub-domain ('domain 1') and a smaller carboxy-terminal sub-domain ('domain 2'). The ATP-binding site of the enzyme lies in the cleft between the two sub-domains. Domain 1 consists of two antiparallel beta sheets flanked by alpha helices, whereas domain 2 consists of a five-stranded beta barrel and a single alpha helix, which form the oligonucleotide-binding fold [
,
]. This region is found in many but not all ATP-dependent DNA ligase enzymes (
). It is thought to constitute part of the catalytic core of ATP dependent DNA ligase [
]. |
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| Protein Domain |
| Name: |
Isoleucine-tRNA ligase, type 1 |
| Type: |
Family |
| Description: |
Isoleucine-tRNA ligase (also known as Isoleucyl-tRNA synthetase)(
) is an alpha monomer that belongs to class Ia. The enzyme, isoleucine-tRNA ligase, activates not only the cognate substrate L-isoleucine but also the minimally distinct L-valine in the first, aminoacylation step. Then, in a second, "editing"step, the ligase itself rapidly hydrolyses only the valylated products [
,
] as shown from the crystal structures. The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [].In eukaryotes, two forms of isoleucine-tRNA synthetase exist, a cytoplasmic form and a mitochondrial form [
]. Type 1 includes bacterial and mitochondrial (gene iars2) isoleucine-tRNA ligases. |
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| Protein Domain |
| Name: |
Galanin precursor |
| Type: |
Family |
| Description: |
Galanin is a peptide hormone that controls various biological activities [
]. Galanin-like immuno-reactivity has been found in the central and peripheral nervous systems of mammals, with high concentrations demonstrated in discrete regions of the central nervous system, including the median eminence, hypothalamus, arcuate nucleus, septum, neuro-intermediate lobe of the pituitary, and the spinal cord. Its localisation within neurosecretory granules suggests that galanin may function as a neurotransmitter, and it has been shown to coexist with a variety of other peptide and amine neurotransmitters within individual neurons [].Although the precise physiological role of galanin is uncertain, it has a number of pharmacological properties: it stimulates food intake, when injected into the third ventricle of rats; it increases levels of plasma growth hormone and prolactin, and decreases dopamine levels in the median eminence [
]; and infusion into humans results in hyperglycemia and glucose intolerance, and inhibits pancreatic release of insulin, somatostatin and pancreatic peptide. Galanin also modulates smooth muscle contractility within the gastro-intestinal and genito-urinary tracts, all such activities suggesting that the hormone may play an important role in the nervous modulation of endocrine and smooth muscle function [
].This family represents the 124 amino acid precursor protein to galanin. The precursor includes a signal peptide, galanin (29 amino acids), and a 60-amino acid galanin mRNA-associated peptide. In the precursor, galanin includes a C-terminal glycine and is flanked on each side by dibasic tryptic cleavage sites. The deduced amino acid sequence of rat galanin is 90% similar to porcine galanin, with all three amino acid differences in the C-terminal heptapeptide. The predicted galanin mRNA-associated peptide includes a 35-amino acid sequence that is 78% similar to the previously reported porcine analogue. This sequence is set off by a single basic tryptic cleavage site and includes a 17-amino acid region that is nearly identical to the porcine counterpart. The high interspecies conservation suggests a biological role for this putative peptide. |
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| Protein Domain |
| Name: |
Restriction endonuclease, type II, AvaI/BsoBI, helical domain |
| Type: |
Homologous_superfamily |
| Description: |
Type II restriction endonucleases (
) are components of prokaryotic DNA restriction-modification mechanisms that protect the organism against invading foreign DNA. These site-specific deoxyribonucleases catalyse the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. Of the 3000 restriction endonucleases that have been characterised, most are homodimeric or tetrameric enzymes that cleave target DNA at sequence-specific sites close to the recognition site. For homodimeric enzymes, the recognition site is usually a palindromic sequence 4-8 bp in length. Most enzymes require magnesium ions as a cofactor for catalysis. Although they can vary in their mode of recognition, many restriction endonucleases share a similar structural core comprising four β-strands and one α-helix, as well as a similar mechanism of cleavage, suggesting a common ancestral origin [
]. However, there is still considerable diversity amongst restriction endonucleases [,
]. The target site recognition process triggers large conformational changes of the enzyme and the target DNA, leading to the activation of the catalytic centres. Like other DNA binding proteins, restriction enzymes are capable of non-specific DNA binding as well, which is the prerequisite for efficient target site location by facilitated diffusion. Non-specific binding usually does not involve interactions with the bases but only with the DNA backbone []. This superfamily represents the helical domain of AvaI and BsoBI restriction endonucleases, both of which recognise the double-stranded sequence CYCGRG (where Y = T/C, and R = A/G) and cleave after C-1 [
]. Structurally, this domain consists of two long alpha helices joined by some shorter ones. One of the longer helices curves inwards towards DNA, while the other is kinked outwards. BsobI is made up of this helical domain, and another more compact globular domain (consisting of smaller helices and some beta strand elements). Within the endonuclease, this domain plays a role in DNA binding, so that the globular (catalytic domain) has a higher concentration of localised substrate []. |
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| Protein Domain |
| Name: |
Condensin II complex subunit H2, middle domain |
| Type: |
Domain |
| Description: |
This is the middle domain of the H2 subunit of the condensin II complex, found in eukaryotes but not fungi. This region represents the disordered section of CNDH2 between the N- and the C-terminal domains.Eukaryotes carry at least two condensin complexes, I and II, each made up of five subunits. The functions of the two complexes are collaborative but non-overlapping. CI appears to be functional in G2 phase in the cytoplasm beginning the process of chromosomal lateral compaction while the CII are concentrated in the nucleus, possibly to counteract the activity of cohesion at this stage. In prophase, CII contributes to axial shortening of chromatids while CI continues to bring about lateral chromatid compaction, during which time the sister chromatids are joined centrally by cohesins. There appears to be just one condensin complex in fungi. CI and CII each contain SMC2 and SMC4 (structural maintenance of chromosomes) subunits, then CI has non-SMC CAP-D2 (CND1), CAP-G (CND3), and CAP-H (CND2). CII has, in addition to the two SMCs, CAP-D3, CAPG2 and CAP-H2. All four of the CAP-D and CAP-G subunits have degenerate HEAT repeats, whereas the CAP-H are kleisins or SMC-interacting proteins (ie they bind directly to the SMC subunits in the complex). The SMC molecules are each long with a small hinge-like knob at the free end of a longish strand, articulating with each other at the hinge. Each strand ends in a knob-like head that binds to one or other end of the CAP-H subunit. The HEAT-repeat containing D and G subunits bind side-by-side between the ends of the H subunit. Activity of the various parts of the complex seem to be triggered by extensive phosphorylations, eg, entry of the complex, in Sch.pombe, into the nucleus during mitosis is promoted by Cdk1 phosphorylation of SMC4/Cut3; and it has been shown that Cdk1 phosphorylates CAP-D3 at Thr1415 in He-La cells thus promoting early stage chromosomal condensation by CII [
,
]. |
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| Protein Domain |
| Name: |
Proline--tRNA ligase, anticodon binding domain |
| Type: |
Domain |
| Description: |
This entry represents the short version of anticodon binding domain found predominantly in bacteria. This domain can be found in proline--tRNA ligase ProRS, which belongs to class II aminoacyl-tRNA synthetase. This domain is responsible for specificity in tRNA-binding, so that the activated amino acid is transferred to a ribose 3' OH group of the appropriate tRNA only [
,
].Prolyl-tRNA synthetase belongs to class IIa. Prolyl-tRNA synthetase (
) exists in two forms, which are loosely related. The first form is present in the majority of eubacteria species. The second one, present in some eubacteria, is essentially present in archaea and eukaryota. This entry contains the first form of prolyl-tRNA synthetase.
The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [
,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c []. |
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| Protein Domain |
| Name: |
Molybdopterin oxidoreductase, prokaryotic, conserved site |
| Type: |
Conserved_site |
| Description: |
A number of different prokaryotic oxidoreductases that require and bind a
molybdopterin cofactor have been shown [,
,
] to share a number of regions of sequence similarity. These enzymes are:Escherichia coli respiratory nitrate reductase (EC 1.7.99.4). This enzyme
complex allows the bacteria to use nitrate as an electron acceptor duringanaerobic growth. The enzyme is composed of three different chains: alpha,
beta and gamma. The alpha chain (gene narG) is the molybdopterin-bindingsubunit. Escherichia coli encodes for a second, closely related, nitrate
reductase complex which also contains a molybdopterin-binding alpha chain(gene narZ).Escherichia coli anaerobic dimethyl sulfoxide reductase (DMSO reductase).
DMSO reductase is the terminal reductase during anaerobic growth on varioussulfoxide and N-oxide compounds. DMSO reductase is composed of three
chains: A, B and C. The A chain (gene dmsA) binds molybdopterin.Escherichia coli biotin sulfoxide reductases (genes bisC and bisZ). This
enzyme reduces a spontaneous oxidation product of biotin, BDS, back tobiotin. It may serve as a scavenger, allowing the cell to use biotin
sulfoxide as a biotin source.Methanobacterium formicicum formate dehydrogenase (EC 1.2.1.2). The alpha
chain (gene fdhA) of this dimeric enzyme binds a molybdopterin cofactor.Escherichia coli formate dehydrogenases -H (gene fdhF), -N (gene fdnG) and
-O (gene fdoG). These enzymes are responsible for the oxidation of formateto carbon dioxide. In addition to molybdopterin, the alpha (catalytic)
subunit also contains an active site, selenocysteine.Wolinella succinogenes polysulfide reductase chain. This enzyme is a
component of the phosphorylative electron transport system with polysulfideas the terminal acceptor. It is composed of three chains: A, B and C. The
A chain (gene psrA) binds molybdopterin.Salmonella typhimurium thiosulfate reductase (gene phsA).
- Escherichia coli trimethylamine-N-oxide reductase (EC 1.6.6.9) (gene torA)[
].Nitrate reductase (EC 1.7.99.4) from Klebsiella pneumoniae (gene nasA),
Alcaligenes eutrophus, Escherichia coli, Rhodobacter sphaeroides,Thiosphaera pantotropha (gene napA), and Synechococcus PCC 7942 (gene
narB).These proteins range from 715 amino acids (fdhF) to 1246 amino acids (narZ) in
size.This entry represents a conserved region located in these enzymes. |
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| Protein Domain |
| Name: |
Serine-tRNA ligase type 2, archaea |
| Type: |
Family |
| Description: |
Serine-tRNA ligase (
) exists as monomer and belongs to class IIa [
].The serine-tRNA ligases from a few of the archaea that belong to this group are different from the set of mutually more closely related serine-tRNA ligases from eubacteria, eukaryotes, and other archaea (
).
There are two distinct types of seryl-tRNA synthetase, as differentiated by primary sequence analysis, three-dimensional structure and substrate recognition mechanism: type 1 (
) is found in the majority of organisms (prokaryotes, eukaryotes and archaea), whereas type 2 (this entry) is confined to some methanogenic archaea [
]. Methanosarcina barkeri possesses two seryl-tRNA synthetases, one of each type [].The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c []. |
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| Protein Domain |
| Name: |
Proline-tRNA ligase, class IIa, type 2 |
| Type: |
Family |
| Description: |
Proline-tRNA ligase (also known as Prolyl-tRNA synthetase) belongs to class IIa. Proline-tRNA ligase(
) exists in two forms, which are loosely related. The first form is present in the majority of eubacteria species. The second one, present in some eubacteria, is essentially present in archaea and eukaryota.
Proline-tRNA ligase catalyzes the attachment of proline to tRNA(Pro) in a two-step reaction: proline is first activated by ATP to form Pro-AMP and then transferred to the acceptor end of tRNA(Pro). It can inadvertently accommodate and process cysteine [
].The proline-tRNA ligaseform presents in most eubacteria can be divided in 2 types. This entry represents proline-tRNA ligase type 2 from eubacteria. The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c []. |
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| Protein Domain |
| Name: |
Prolyl-tRNA synthetase, class IIa, type 1 |
| Type: |
Family |
| Description: |
The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [].Proline-tRNA ligase (also known as Prolyl-tRNA synthetase) belongs to class IIa. Proline-tRNA ligase(
) exists in two forms, which are loosely related. The first form is present in the majority of eubacteria species. The second one, present in some eubacteria, is essentially present in archaea and eukaryota.
The prolyl-tRNA synthetase form presents in most eubacteria can be divided in 2 types. This entry represents type 1. This family includes the enzyme from Escherichia coli that contains all three of the conserved consensus motifs characteristic of class II aminoacyl-tRNA synthetases [
]. |
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| Protein Domain |
| Name: |
Phosphotransferase system, EIIC component, type 3 |
| Type: |
Domain |
| Description: |
The phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS) [
,
]
is a major carbohydrate transport system in bacteria. The PTS catalyzes thephosphorylation of incoming sugar substrates concomitant with their
translocation across the cell membrane. The general mechanism of the PTS isthe following: a phosphoryl group from phosphoenolpyruvate (PEP) is
transferred to enzyme I (EI) of PTS which in turn transfers it to a phosphorylcarrier protein (HPr). Phospho-HPr then transfers the
phosphoryl group to a sugar-specific permease which consists of at least threestructurally distinct domains (IIA, IIB, and IIC), [
] which can either be fused together in a single polypeptide chain or exist as two or threeinteractive chains, formerly called enzymes II (EII) and III (EIII).
The first domain (IIA), carries the first permease-specific
phosphorylation site, an histidine which is phosphorylated by phospho-HPr. Thesecond domain (IIB) is phosphorylated by phospho-IIA on a
cysteinyl or histidyl residue, depending on the sugar transported. Finally,the phosphoryl group is transferred from the IIB domain to the sugar substrate
concomitantly with the sugar uptake processed by the IIC domain. The IICdomain forms the translocation channel and the specific substrate-binding
site. An additional transmembrane domain IID, homologous toIIC, can be found in some PTSs, e.g. for mannose [
,
,
,
,
].According to sequence analyses [
,
,
,
], the PTS EIIC domain can be dividedin five groups.
The PTS EIIC type 1 domain is found in the Glucose class of PTS and has an
average length of about 80 amino acids.The PTS EIIC type 2 domain is found in the Mannitol class of PTS and has an
average length of about 90 amino acids.The PTS EIIC type 3 domain is found in the Lactose class of PTS and has an
average length of about 100 amino acids.The PTS EIIC type 4 domain is found in the Mannose class of PTS and has an
average length of about 160 amino acids.The PTS EIIC type 5 domain is found in the Sorbitol class of PTS and has an
average length of about 190 amino acids. |
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| Protein Domain |
| Name: |
N-glycosylase/DNA lyase |
| Type: |
Family |
| Description: |
Oxidative damage represents a major threat to genomic stability, as the major product of DNA oxidation, 8-oxoguanine (GO), frequently mispairs with adenine during replication. In order to prevent these mutagenic events, organisms have evolved GO-DNA glycosylases (or N-glycosylase/DNA lyases) that remove this oxidized base from DNA [
]. GO is removed from DNA predominantly by the base excision repair (BER) pathway. This process is initiated by 8-oxoguanine-DNA glycosylases, which cleave the N-glycosidic bond between the aberrant base and the sugar-phosphate backbone to generate an apurinic (AP) site. Some DNA glycosylases possess also an intrinsic AP lyase activity, which cleaves the phosphodiester bond 3' from the AP site by beta- or beta, delta-elimination, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate [].This group represents archaeal GO-DNA glycosylases (AGOG). Pyrobaculum aerophilum PAE2237 has been shown to remove GO from single- and double-stranded substrates with great efficiency [
]. It has both GO-DNA glycosylase and AP-lyase () activities [
].Archaeal GO-DNA glycosylases are not closely related to other DNA glycosylases. However, they share with the other HhH-GPD DNA glycosylase families the overall fold and the general active site architecture. AGOG possesses the principal hallmark of GO-DNA glycosylases: a helix-hairpin-helix motif and a glycine/proline-rich sequence followed by an absolutely conserved aspartate (HhH-GPD motif) [
]. It contains two α-helical subdomains, with the 8-oxoguanine binding site located in a cleft at their interface [
]. AGOG belongs to a new class within the helix-hairpin-helix (HhH) superfamily of DNA repair enzymes. Its hairpin structure differs substantially from that of other proteins containing an HhH motif, and is predicted that to interact with the DNA backbone in a distinct manner. Furthermore, the mode of 8-oxoguanine recognition, which involves several hydrogen-bonding and pi-stacking interactions, is unlike that observed in human OGG1, the prototypic 8-oxoguanine HhH-type DNA glycosylase. Despite these differences, the predicted kinked conformation of bound DNA and the catalytic mechanism are likely to resemble those of human OGG1 []. |
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| Protein Domain |
| Name: |
Hydroxymethylglutaryl-CoA reductase, bacterial-type |
| Type: |
Family |
| Description: |
There are two distinct classes of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase enzymes: class I consists of eukaryotic and most archaeal enzymes (
), while class II consists of prokaryotic enzymes (
) [
,
].Class I HMG-CoA reductases catalyse the NADP-dependent synthesis of mevalonate from 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). In vertebrates, membrane-bound HMG-CoA reductase is the rate-limiting enzyme in the biosynthesis of cholesterol and other isoprenoids. In plants, mevalonate is the precursor of all isoprenoid compounds [
]. The reduction of HMG-CoA to mevalonate is regulated by feedback inhibition by sterols and non-sterol metabolites derived from mevalonate, including cholesterol. In archaea, HMG-CoA reductase is a cytoplasmic enzyme involved in the biosynthesis of the isoprenoids side chains of lipids []. Class I HMG-CoA reductases consist of an N-terminal membrane domain (lacking in archaeal enzymes), and a C-terminal catalytic region. The catalytic region can be subdivided into three domains: an N-domain (N-terminal), a large L-domain, and a small S-domain (inserted within the L-domain). The L-domain binds the substrate, while the S-domain binds NADP.Class II HMG-CoA reductases catalyse the reverse reaction of class I enzymes, namely the NAD-dependent synthesis of HMG-CoA from mevalonate and CoA [
]. Some bacteria, such as Pseudomonas mevalonii, can use mevalonate as the sole carbon source. Class II enzymes lack a membrane domain. Their catalytic region is structurally related to that of class I enzymes, but it consists of only two domains: a large L-domain and a small S-domain (inserted within the L-domain). As with class I enzymes, the L-domain binds substrate, but the S-domain binds NAD (instead of NADP in class I).This entry represents class II HMG-CoA reductases, as well as some class I enzymes from archaea. This family was built from two class II NAD-dependent enzymes from organisms closely related to Pseudomonas mevalonii, a bacterium that can use mevalonate as its sole carbon source. Some archaeal HMG-CoA reductases were found to be of bacterial origin [
]. This family is occasionally found together with a thiolase (
) to form a putative bifunctional acetyl-CoA acetyltransferase/HMG-CoA reductase protein [
]. |
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| Protein Domain |
| Name: |
Fungal ligninase |
| Type: |
Family |
| Description: |
Peroxidases are haem-containing enzymes that use hydrogen peroxide as the electron acceptor to catalyse a number of oxidative reactions. Peroxidases are found in bacteria, fungi, plants and animals. Fungal ligninases are extracellular haem enzymes involved in the degradation of lignin. They include lignin peroxidases (LiPs), manganese-dependent peroxidases (MnPs) and versatile peroxidases, which combine the substrate-specificity characteristics of the other two [
]. In MnP, Mn2+serves as the reducing substrate [
].It is commonly thought that the plant polymer lignin is the second most abundant organic compound on Earth, exceeded only by cellulose. Higher plants synthesise vast quantities of insoluble macromolecules, including lignins. Lignin is an amorphous three-dimensional aromatic biopolymer composed of oxyphenylpropane units. Biodegradation of lignins is slow - it is probable that their decomposition is the rate-limiting step in the biospheric carbon-oxygen cycle, which is mediated almost entirely by the catabolic activities of microorganisms. The white-rot fungi are able extensively to decompose all the important structural components of wood, including both cellulose and lignin. Under the proper environmental conditions, white-rot fungi completely degrade all structural components of lignin, with ultimate formation of CO
2and H
2O. The first step in lignin degradation is depolymerisation, catalysed by the LiPs (ligninases). LiPs are secreted, along with hydrogen peroxide (H
2O
2), by white-rot fungi under conditions of nutrient limitation. The enzymes are not only important in lignin biodegradation, but are also potentially valuable in chemical waste disposal because of their ability to degrade environmental pollutants [].To date, 3D structures have been determined for LiP [
] and MnP [] from Phanerochaete chrysosporium (White-rot fungus), and for the fungal peroxidase from Arthromyces ramosus []. All these proteins share the same architecture and consist of 2 all-alpha domains, between which is embedded the haem group. The helical topography of LiPs is nearly identical to that of yeast cytochrome c peroxidase (CCP) [], despite the former having four disulphide bonds, which are absent in CCP (MnP has an additional disulphide bond at the C terminus). |
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| Protein Domain |
| Name: |
4-dedimethylamino-4-oxo-anhydrotetracycline transaminase OxyQ |
| Type: |
Family |
| Description: |
Two lysine biosynthesis pathways evolved separately in organisms, the diaminopimelic acid (DAP) and aminoadipic acid (AAA) pathways. The DAP pathway synthesizes L-lysine from aspartate and pyruvate, and diaminopimelic acid is an intermediate. This pathway is utilised by most bacteria, some archaea, some fungi, some algae, and plants. The AAA pathway synthesizes L-lysine from alpha-ketoglutarate and acetyl coenzyme A (acetyl-CoA), and alpha-aminoadipic acid is an intermediate. This pathway is utilised by most fungi, some algae, the bacterium Thermus thermophilus, and probably some archaea, such as Sulfolobus, Thermoproteus, and Pyrococcus. No organism is known to possess both pathways [
].There four known variations of the DAP pathway in bacteria: the succinylase, acetylase, aminotransferase, and dehydrogenase pathways. These pathways share the steps converting L-aspartate to L-2,3,4,5- tetrahydrodipicolinate (THDPA), but the subsequent steps leading to the production of meso-diaminopimelate, the immediate precursor of L-lysine, are different [
].The succinylase pathway acylates THDPA with succinyl-CoA to generate N-succinyl-LL-2-amino-6-ketopimelate and forms meso-DAP by subsequent transamination, desuccinylation, and epimerization. This pathway is utilised by proteobacteria and many firmicutes and actinobacteria. The acetylase pathway is analogous to the succinylase pathway but uses N-acetyl intermediates. This pathway is limited to certain Bacillus species, in which the corresponding genes have not been identified. The aminotransferase pathway converts THDPA directly to LL-DAP by diaminopimelate aminotransferase (DapL) without acylation. This pathway is shared by cyanobacteria, Chlamydia, the archaeon Methanothermobacter thermautotrophicus, and the plant Arabidopsis thaliana. The dehydrogenase pathway forms meso-DAP directly from THDPA, NADPH, and NH4 _ by using diaminopimelate dehydrogenase (Ddh). This pathway is utilised by some Bacillus and Brevibacterium species and Corynebacterium glutamicum. Most bacteria use only one of the four variants, although certain bacteria, such as C. glutamicum and Bacillus macerans, possess both the succinylase and dehydrogenase pathways.This family of actinobacterial proteins are involved in the biosynthesis of the tetracycline antibiotic, oxytetracycline. The minimum set of enzymes required for the biosynthesis of anhydrotetracycline, the first intermediate in the synthesis of oxytetracycline, are OxyL, OxyQ, and OxyT. OxyQ catalyzes the conversion of 4-dedimethylamino-4-oxoanhydrotetracycline to yield 4-amino-4-de(dimethylamino)anhydrotetracycline (4-amino-ATC) [
]. |
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| Protein Domain |
| Name: |
Glutamate-tRNA synthetase, class I, anticodon-binding domain, subdomain 1 |
| Type: |
Homologous_superfamily |
| Description: |
The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [].Structurally, an α-helix-bundle anticodon-binding domain characterises the class Ia synthetases, whereas the class Ib synthetases, GlnRS and GluRS have distinct anticodon-binding domains. The anticodon-binding domain has a multi-helical structure, consisting of two all-alpha subdomains. The Rossmann-fold, made up of alternate α-helices and β-sheets involved in ATP binding in the extended conformation, and the anticodon-binding domains are connected by a beta-α-α-beta-alpha topology ('SC fold') domain that contains the class I specific KMSKS motif [
,
]. This superfamily represents the anticodon-binding domain 1 from Glutamate-tRNA synthetase. |
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| Protein Domain |
| Name: |
DNA-directed DNA polymerase, family A, conserved site |
| Type: |
Conserved_site |
| Description: |
DNA carries the biological information that instructs cells how to exist
in an ordered fashion: accurate replication is thus one of the mostimportant events in the cell life cycle. This function is mediated by
DNA-directed DNA-polymerases, which add nucleotide triphosphate (dNTP)residues to the 3'-end of the growing DNA chain, using a complementary DNA as template. Small RNA molecules are generally used as primers for
chain elongation, although terminal proteins may also be used. Three motifs, A, B and C [], are seen to be conserved across all DNA-polymerases, with motifs A and C also seen in RNA- polymerases. They are centred on invariant residues, and their structural significance was implied from the Klenow (Escherichia coli) structure: motif A contains a strictly-conserved aspartate at the junction of a β-strand and an α-helix; motif B contains an α-helix with positive charges; and motif C has a doublet of negative charges, located in a β-turn-beta secondary structure [].DNA polymerases (
) can be classified, on the basis of sequence
similarity [,
], into at least four different groups: A, B, C and X. Members of family X are small (about 40kDa) compared with other polymerases and encompass two distinct polymerase enzymes that have similar functionality: vertebrate polymerase beta (same as yeast pol 4), and terminal deoxynucleotidyl-transferase (TdT) (). The former functions in DNA repair, while
the latter terminally adds single nucleotides to polydeoxynucleotide chains.Both enzymes catalyse addition of nucleotides in a distributive manner, i.e. they
dissociate from the template-primer after addition of each nucleotide.DNA-polymerases show a degree of structural similarity with RNA-polymerases.
Five regions of similarity are found in all the polymerases of this entry. The signature of this entry is to the conserved region, known as 'motif B' [
]; motif B is located in a domain which, in E. coli polA, has been shown to bind deoxynucleotide triphosphate substrates; it contains a conserved tyrosine which has been shown, by photo-affinity labelling, to be in the active site; a conserved lysine, also part of this motif, can be chemically labelled, using pyridoxal phosphate. |
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| Protein Domain |
| Name: |
Neuropeptide FF receptor, type 2 |
| Type: |
Family |
| Description: |
Neuropeptide FF receptors [
] belong to a family of neuropeptides containing an RF-amide motif at their C terminus which have a high affinity for the pain modulatory peptide neuropeptide NPFF (NPFF) [
]. Neuropeptide FF (NPFF) receptors have two subtypes, neuropeptide FF receptor type 1 (NPFF1) and neuropeptide FF receptor type 2 (NPFF2), they are members of rhodopsin G protein-coupled receptor family. The neuropeptide FF is found at high concentrations in the posterior pituitary, spinal cord, hypothalamus and medulla and is believed to be involved in pain modulation, opioid tolerance, cardiovascular regulation, memory and neuroendocrine regulation [,
,
,
].Comparing the distribution of NPFF1 and NPFF2 receptors in different species reveals important species differences [
]. The NPFF1 receptor is broadly distributed in the central nervous system with the highest levels found in the limbic system and the hypothalamus, is thought to participate in neuroendocrine functions. Whereas as the NPFF2 receptor is present in high density, particularly in mammals in the superficial layers of the spinal cord [] where it is involved in nociception and modulation of opioid functions [], consistent with a potential role of NPFF in the modulation of sensory inputs, like pain responses [,
,
].This entry represents NPFF2, which is expressed at high levels in the thymus and placenta, with moderate levels in the pituitary, spleen, testis and brain. Low levels were detected in the spinal cord, pancreas, small intestine, uterus, stomach, lung, heart and skeletal muscle. No expression was detected in liver or kidney [
]. The NPFF2 receptor has been found to regulate adenylyl cyclase in some recombinant cell lines [,
]. In acutely dissociated neurons, the NPFF2 receptors specifically counteract N-type Ca2+ channel inhibition by opioids [,
]. In SH-SY5Y neuroblastoma cells stably expressing human NPFF receptors, NPFF agonists also reduce the inhibitory effect of mu-opioid and delta-opioid receptor activation on an N-type Ca2+ channel [,
]. These regulations could be due in part to receptor heteromerisation since NPFF2 receptors have been shown to physically interact with mu-opiod receptors []] and induce their trans-phosphorylations []. |
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| Protein Domain |
| Name: |
Two pore domain potassium channel, TASK family |
| Type: |
Family |
| Description: |
2P-domain channels influence the resting membrane potential and as a result can control cell excitability. In addition, they pass K+
in response to changes in membrane potential, and are also tightly regulated by molecular oxygen, GABA (gamma-aminobutyric acid), noradrenaline and serotonin.The first member of this family (TOK1), cloned from Saccharomyces cerevisiae [
], ispredicted to have eight potential transmembrane (TM) helices. However,
subsequently-cloned two P-domain family members from Drosophila andmammalian species are predicted to have only four TM segments. They are
usually referred to as TWIK-related channels (Tandem of P-domains in a Weakly Inward rectifying K+ channel) [
,
,
,
]. Functional characterisation of these channels has revealed a diversity of properties in that they may show inward or outward rectification, their activity may be modulated in different directions by protein phosphorylation, and their sensitivity to changes in intracellular or extracellular pH varies. Despite these disparate properties, they are all thought to share the same topology offour TM segments, including two P-domains. That TWIK-related K+ channels
all produce instantaneous and non-inactivating K+ currents, which do notdisplay a voltage-dependent activation threshold, suggests that they are
background (leak) K+ channels involved in the generation and modulation of the resting membrane potential in various cell types. Further studies have revealed that they may be found in many species, including: plants, invertebrates and mammals.TASK is a member of the TWIK-related (two P-domain) K
+channel family
identified in human tissues []. It is widely distributed, being particularly abundant in the pancreas and placenta, but it is also found inthe brain, heart, lung and kidney. Its amino acid identity to TWIK-1 and TREK-1 is rather low, being about 25-28%. However, it is thought to share the same topology of four TM segments, with two P-domains. TASK is very sensitive to variations in extracellular pH in the physiological range, changing from fully-open to closed in approximately 0.5 pH units around pH 7.4. Thus, it may well be a biological sensor of external pH variations.
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| Protein Domain |
| Name: |
Peptidase S48, DNA-binding transcriptional activator HetR |
| Type: |
Family |
| Description: |
Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes [
]. They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence []. Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases [].Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base [
]. The geometric orientations of the catalytic residues are similar between families, despite different protein folds []. The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) [,
].This group of serine peptidases, which includes HetR, are associated with heterocystous cyanobacteria and belong to MEROPS peptidase family S48 (clan S-). HetR is a DNA-binding serine-type protease required for heterocyst differentiation in heterocystous cyanobacteria under conditions of nitrogen deprivation. Mutation of HetR from of Anabaena sp. (strain PCC 7120) by site-specific mutagenesis of Ser-152 showed that this residue was one of the peptidase active site residues. It was suggested that peptidase activity might be needed for repression of HetR overproduction under conditions of nitrogen deprivation [
]. Modification of Cys-48 prevented disulphide-bond formation and homodimerisation of HetR and DNA-binding. The homodimer of HetR binds the promoter regions of hetR, hepA, and patS, suggesting a direct control of the expression of these genes by HetR. The pentapeptide RGSGR, which is present at the C terminus of PatS, blocks heterocyst formation, inhibits the DNA binding of HetR and prevents hetR up-regulation [
]. |
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| Protein Domain |
| Name: |
Phenylalanyl-tRNA synthetase |
| Type: |
Domain |
| Description: |
The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [].Phenylalanyl-tRNA synthetase (
) is an alpha2/beta2 tetramer composed of 2 subunits that belongs to class IIc. In eubacteria, a small subunit (pheS gene) can be designated as beta (E. coli) or alpha subunit (nomenclature adopted in InterPro). Reciprocally the large subunit
(pheT gene) can be designated as alpha (E. coli) or beta (see and
). In all other kingdoms the two subunits have equivalent length in eukaryota, and can be identified by specific signatures. The enzyme from Thermus thermophilus has an alpha 2 beta 2 type quaternary structure and is one of the most complicated members of the synthetase family. Identification of phenylalanyl-tRNA synthetase as a member of class II aaRSs was based only on sequence alignment of the small alpha-subunit with other synthetases [
]. |
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| Protein Domain |
| Name: |
Peptidase M1, membrane alanine aminopeptidase |
| Type: |
Domain |
| Description: |
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 M1 (clan MA(E)), the type example being aminopeptidase N from Homo sapiens (Human). The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA.Membrane alanine aminopeptidase ()
is part of the HEXXH+E
group; it consists entirely of aminopeptidases, spread across a widevariety of species [
]. Functional studies show that CD13/APN catalyzes the removal of single amino acids from the amino terminus of small peptides and probably plays a role in their final digestion; one family member (leukotriene-A4 hydrolase) is known to hydrolyse the epoxide leukotriene-A4to form an inflammatory mediator [
]. This hydrolase has been shown tohave aminopeptidase activity [
], and the zinc ligands of the M1 familywere identified by site-directed mutagenesis on this enzyme [
] CD13 participates in trimming peptides bound to MHC class II molecules [] and cleaves MIP-1 chemokine, which alters target cell specificity from basophils to eosinophils []. CD13 acts as a receptor for specific strains of RNA viruses (coronaviruses) which cause a relatively large percentage of upper respiratorytract infections.
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| Protein Domain |
| Name: |
DNA topoisomerase, type IIA |
| Type: |
Family |
| Description: |
DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single- or double-strand breaks, crossing the strands through one another, then resealing the breaks [
]. These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis [,
]. DNA topoisomerases are divided into two classes: type I enzymes (; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (
; topoisomerases II, IV and VI) break double-strand DNA [
].Type II topoisomerases are ATP-dependent enzymes, and can be subdivided according to their structure and reaction mechanisms: type IIA (topoisomerase II or gyrase, and topoisomerase IV) and type IIB (topoisomerase VI). These enzymes are responsible for relaxing supercoiled DNA as well as for introducing both negative and positive supercoils [
].Type IIA topoisomerases together manage chromosome integrity and topology in cells. Topoisomerase II (called gyrase in bacteria) primarily introduces negative supercoils into DNA. In bacteria, topoisomerase II consists of two polypeptide subunits, gyrA and gyrB, which form a heterotetramer: (BA)2. In most eukaryotes, topoisomerase II consists of a single polypeptide, where the N- and C-terminal regions correspond to gyrB and gyrA, respectively; this topoisomerase II forms a homodimer that is equivalent to the bacterial heterotetramer. There are four functional domains in topoisomerase II: domain 1 (N-terminal of gyrB) is an ATPase, domain 2 (C-terminal of gyrB) is responsible for subunit interactions (differs between eukaryotic and bacterial enzymes), domain 3 (N-terminal of gyrA) is responsible for the breaking-rejoining function through its capacity to form protein-DNA bridges, and domain 4 (C-terminal of gyrA) is able to non-specifically bind DNA [
].Topoisomerase IV primarily decatenates DNA and relaxes positive supercoils, which is important in bacteria, where the circular chromosome becomes catenated, or linked, during replication [
]. Topoisomerase IV consists of two polypeptide subunits, parE and parC, where parC is homologous to gyrA and parE is homologous to gyrB.This entry represents DNA topoisomerase, type IIA. |
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| Protein Domain |
| Name: |
DNA topoisomerase, type IIA, subunit B, domain 2 |
| Type: |
Domain |
| Description: |
DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single- or double-strand breaks, crossing the strands through one another, then resealing the breaks [
]. These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis [,
]. DNA topoisomerases are divided into two classes: type I enzymes (; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (
; topoisomerases II, IV and VI) break double-strand DNA [
].Type II topoisomerases are ATP-dependent enzymes, and can be subdivided according to their structure and reaction mechanisms: type IIA (topoisomerase II or gyrase, and topoisomerase IV) and type IIB (topoisomerase VI). These enzymes are responsible for relaxing supercoiled DNA as well as for introducing both negative and positive supercoils [
].Type IIA topoisomerases together manage chromosome integrity and topology in cells. Topoisomerase II (called gyrase in bacteria) primarily introduces negative supercoils into DNA. In bacteria, topoisomerase II consists of two polypeptide subunits, gyrA and gyrB, which form a heterotetramer: (BA)2. In most eukaryotes, topoisomerase II consists of a single polypeptide, where the N- and C-terminal regions correspond to gyrB and gyrA, respectively; this topoisomerase II forms a homodimer that is equivalent to the bacterial heterotetramer. There are four functional domains in topoisomerase II: domain 1 (N-terminal of gyrB) is an ATPase, domain 2 (C-terminal of gyrB) is responsible for subunit interactions, domain 3 (N-terminal of gyrA) is responsible for the breaking-rejoining function through its capacity to form protein-DNA bridges, and domain 4 (C-terminal of gyrA) is able to non-specifically bind DNA [
].Topoisomerase IV primarily decatenates DNA and relaxes positive supercoils, which is important in bacteria, where the circular chromosome becomes catenated, or linked, during replication [
]. Topoisomerase IV consists of two polypeptide subunits, parE and parC, where parC is homologous to gyrA and parE is homologous to gyrB.This entry represents the second domain found in subunit B (gyrB and parE) of bacterial gyrase and topoisomerase IV, and the equivalent N-terminal region in eukaryotic topoisomerase II composed of a single polypeptide. |
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| Protein Domain |
| Name: |
DNA topoisomerase, type IIA, subunit B, C-terminal |
| Type: |
Homologous_superfamily |
| Description: |
DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single- or double-strand breaks, crossing the strands through one another, then resealing the breaks [
]. These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis [,
]. DNA topoisomerases are divided into two classes: type I enzymes (; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (
; topoisomerases II, IV and VI) break double-strand DNA [
].Type II topoisomerases are ATP-dependent enzymes, and can be subdivided according to their structure and reaction mechanisms: type IIA (topoisomerase II or gyrase, and topoisomerase IV) and type IIB (topoisomerase VI). These enzymes are responsible for relaxing supercoiled DNA as well as for introducing both negative and positive supercoils [
].Type IIA topoisomerases together manage chromosome integrity and topology in cells. Topoisomerase II (called gyrase in bacteria) primarily introduces negative supercoils into DNA. In bacteria, topoisomerase II consists of two polypeptide subunits, gyrA and gyrB, which form a heterotetramer: (BA)2. In most eukaryotes, topoisomerase II consists of a single polypeptide, where the N- and C-terminal regions correspond to gyrB and gyrA, respectively; this topoisomerase II forms a homodimer that is equivalent to the bacterial heterotetramer. There are four functional domains in topoisomerase II: domain 1 (N-terminal of gyrB) is an ATPase, domain 2 (C-terminal of gyrB) is responsible for subunit interactions (differs between eukaryotic and bacterial enzymes), domain 3 (N-terminal of gyrA) is responsible for the breaking-rejoining function through its capacity to form protein-DNA bridges, and domain 4 (C-terminal of gyrA) is able to non-specifically bind DNA [].Topoisomerase IV primarily decatenates DNA and relaxes positive supercoils, which is important in bacteria, where the circular chromosome becomes catenated, or linked, during replication [
]. Topoisomerase IV consists of two polypeptide subunits, parE and parC, where parC is homologous to gyrA and parE is homologous to gyrB.This superfamily represents the C-terminal domain of subunit B (gyrB and parE) of bacterial gyrase and topoisomerase IV, and the equivalent region in eukaryotic topoisomerase II composed of a single polypeptide. |
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| Protein Domain |
| Name: |
DNA topoisomerase, type IIA, domain A, alpha-beta |
| Type: |
Homologous_superfamily |
| Description: |
DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single- or double-strand breaks, crossing the strands through one another, then resealing the breaks [
]. These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis [,
]. DNA topoisomerases are divided into two classes: type I enzymes (; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (
; topoisomerases II, IV and VI) break double-strand DNA [
].Type II topoisomerases are ATP-dependent enzymes, and can be subdivided according to their structure and reaction mechanisms: type IIA (topoisomerase II or gyrase, and topoisomerase IV) and type IIB (topoisomerase VI). These enzymes are responsible for relaxing supercoiled DNA as well as for introducing both negative and positive supercoils [
].Type IIA topoisomerases together manage chromosome integrity and topology in cells. Topoisomerase II (called gyrase in bacteria) primarily introduces negative supercoils into DNA. In bacteria, topoisomerase II consists of two polypeptide subunits, gyrA and gyrB, which form a heterotetramer: (BA)2. In most eukaryotes, topoisomerase II consists of a single polypeptide, where the N- and C-terminal regions correspond to gyrB and gyrA, respectively; this topoisomerase II forms a homodimer that is equivalent to the bacterial heterotetramer. There are four functional domains in topoisomerase II: domain 1 (N-terminal of gyrB) is an ATPase, domain 2 (C-terminal of gyrB) is responsible for subunit interactions (differs between eukaryotic and bacterial enzymes), domain 3 (N-terminal of gyrA) is responsible for the breaking-rejoining function through its capacity to form protein-DNA bridges, and domain 4 (C-terminal of gyrA) is able to non-specifically bind DNA [
].Topoisomerase IV primarily decatenates DNA and relaxes positive supercoils, which is important in bacteria, where the circular chromosome becomes catenated, or linked, during replication [
]. Topoisomerase IV consists of two polypeptide subunits, parE and parC, where parC is homologous to gyrA and parE is homologous to gyrB.This superfamily represents the α-β domain of subunit A (gyrA and parC) of bacterial gyrase and topoisomerase IV, and the equivalent C-terminal region in eukaryotic topoisomerase II composed of a single polypeptide. |
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| Protein Domain |
| Name: |
DNA topoisomerase, type IA, zn finger |
| Type: |
Domain |
| Description: |
DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single- or double-strand breaks, crossing the strands through one another, then resealing the breaks [
]. These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis [,
]. DNA topoisomerases are divided into two classes: type I enzymes (; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (
; topoisomerases II, IV and VI) break double-strand DNA [
].Type I topoisomerases are ATP-independent enzymes (except for reverse gyrase), and can be subdivided according to their structure and reaction mechanisms: type IA (Topo IA; bacterial and archaeal topoisomerase I, topoisomerase III and reverse gyrase) and type IB (Topo IB; eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA. This function is vital for the processes of replication, transcription, and recombination. Unlike Topo IA enzymes, Topo IB enzymes do not require a single-stranded region of DNA or metal ions for their function. The type IB family of DNA topoisomerases includes eukaryotic nuclear topoisomerase I, topoisomerases of poxviruses, and bacterial versions of Topo IB []. They belong to the superfamily of DNA breaking-rejoining enzymes, which share the same fold in their C-terminal catalytic domain and the overall reaction mechanism with tyrosine recombinases [,
]. The C-terminal catalytic domain in topoisomerases is linked to a divergent N-terminal domain that shows no sequence or structure similarity to the N-terminal domains of tyrosine recombinases [,
].This entry represents the zinc-finger domain found in type IA topoisomerases, including bacterial and archaeal topoisomerase I and III enzymes, and in eukaryotic topoisomerase III enzymes. Escherichia coli topoisomerase I proteins contain five copies of a zinc-ribbon-like domain at their C terminus, two of which have lost their cysteine residues and are therefore probably not able to bind zinc [
]. This domain is still considered to be a member of the zinc-ribbon superfamily despite not being able to bind zinc. |
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| Protein Domain |
| Name: |
Tryptophan-tRNA ligase |
| Type: |
Family |
| Description: |
This entry represents tryptophan-tRNA ligase (TrpRS; also known as tryptophanyl-tRNA synthetase) (
). The enzyme is widely distributed, being found in archaea, bacteria and eukaryotes. TrpRS is a homodimer which attaches Tyr to the appropriate tRNA. TrpRS is a class I tRNA synthetase, so it aminoacylates the 2'-OH of the nucleotide at the 3' end of the tRNA. The core domain is based on the Rossman fold and is responsible for the ATP-dependent formation of the enzyme bound aminoacyl-adenylate. It contains class I characteristic 'HIGH' and 'KMSKS' motifs, which are involved in ATP binding [
].The class Ia aminoacyl-tRNA synthetases consist of the isoleucyl, methionyl, valyl, leucyl, cysteinyl, and arginyl-tRNA synthetases; the class Ib include the glutamyl and glutaminyl-tRNA synthetases, and the class Ic are the tyrosyl and tryptophanyl-tRNA synthetases [
].The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c []. |
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| Protein Domain |
| Name: |
Tyrosine-tRNA ligase, archaeal/eukaryotic-type |
| Type: |
Family |
| Description: |
Tyrosine-tRNA ligases (TyrRS; also known as Tyrosyl-tRNA synthetases) (
) are widely distributed, being found in archaea, bacteria and eukaryotes. TyrRS is a homodimer which attaches Tyr to the appropriate tRNA. TyrRS is a class I tRNA synthetases, so it aminoacylates the 2'-OH of the nucleotide at the 3' end of the tRNA. The core domain is based on the Rossman fold and is responsible for the ATP-dependent formation of the enzyme bound aminoacyl-adenylate. It contains the class I characteristic 'HIGH' and 'KMSKS' motifs, which are involved in ATP binding. Studies have shown that the 'KMSKS' motif plays a role in the initial binding of tRNA(Tyr) to tyrosine-tRNA ligase [
].The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [].Two groups can be distinguished among tyrosyl-tRNA synthetases. One group contains bacterial and organellar eukaryotic examples. The other contains archaeal and cytosolic eukaryotic examples. This entry represents the archaeal and cytosolic eukaryotic tyrosyl-tRNA synthetases. |
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| Protein Domain |
| Name: |
Glycine-tRNA ligase, beta subunit |
| Type: |
Family |
| Description: |
This entry represents the beta subunit of glycine-tRNA ligase. In most eubacteria, glycine-tRNA ligase (
) is an alpha2/beta2 tetramer composed of 2 different subunits [
,
,
] while in archaea, eukaryota and some eubacteria, glycine-tRNA ligase is an alpha2 dimer (see ). This entry represents the beta subunit of the tetrameric enzyme. What is most interesting
is the lack of similarity between the two types: divergence at the sequencelevel is so great that it is impossible to infer descent from common genes.
The alpha (see ) and beta subunits also lack significant sequence similarity.
However, they are translated from a single mRNA [], and a single chain glycine-tRNA ligase from Chlamydia trachomatis has been found to have
significant similarity with both domains, suggesting divergence from a single polypeptide chain [
].The aminoacyl-tRNA synthetases (
) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction. These proteins differ widely in size and oligomeric state, and have limited sequence homology [
]. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold and are mostly monomeric, while class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet formation, flanked by α-helices [], and are mostly dimeric or multimeric. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic aci, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan and valine belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, lysine, phenylalanine, proline, serine, and threonine belong to class-II synthetases.The 10 class I synthetases are considered to have in common the catalytic domain structure based on the Rossmann fold, which is totally different from the class II catalytic domain structure. The class I synthetases are further divided into three subclasses, a, b and c, according to sequence homology. No conserved structural features for tRNA recognition by class I synthetases have been established. |
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| Protein Domain |
| Name: |
Peptidase M17, leucyl aminopeptidase, N-terminal |
| Type: |
Domain |
| Description: |
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 []. |
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| Protein Domain |
| Name: |
Peptidase M17, leucyl aminopeptidase, C-terminal |
| Type: |
Domain |
| Description: |
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 residuesfrom 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 2 zinc ions and the active site are entirely located in the C-terminal catalytic domain []. |
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| Protein Domain |
| Name: |
RNA polymerase III subunit RPC82-related, helix-turn-helix |
| Type: |
Domain |
| Description: |
DNA-directed RNA polymerases
(also known as DNA-dependent RNA polymerases) are responsible for the polymerisation of ribonucleotides into a sequence complementary to the template DNA. In eukaryotes, there are three different forms of DNA-directed RNA polymerases transcribing different sets of genes. Most RNA polymerases are multimeric
enzymes and are composed of a variable number of subunits. The core RNA polymerase complex consists of five subunits (two alpha, one beta, one beta-prime and one omega) and is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme []. The core RNA polymerase complex forms a "crab claw"-like structure with an internal channel running along the full length [
]. The key functional sites of the enzyme, as defined by mutational and cross-linking analysis, are located on the inner wall of this channel.RNA synthesis follows after the attachment of RNA polymerase to a specific site, the promoter, on the template DNA strand. The RNA synthesis process continues until a termination sequence is reached. The RNA product, which is synthesised in the 5' to 3' direction, is known as the primary transcript.
Eukaryotic nuclei contain three distinct types of RNA polymerases that differ in the RNA they synthesise:RNA polymerase I: located in the nucleoli, synthesises precursors of most ribosomal RNAs.RNA polymerase II: occurs in the nucleoplasm, synthesises mRNA precursors. RNA polymerase III: also occurs in the nucleoplasm, synthesises the precursors of 5S ribosomal RNA, the tRNAs, and a variety of other small nuclear and cytosolic RNAs. Eukaryotic cells are also known to contain separate mitochondrial and chloroplast RNA polymerases. Eukaryotic RNA polymerases, whose molecular masses vary in size from 500 to 700kDa, contain two non-identical large (>100kDa) subunits and an array of up to 12 different small (less than 50kDa) subunits.This family consists of several DNA-directed RNA polymerase III polypeptides which are related to the Saccharomyces cerevisiae (Baker's yeast) RPC82 protein. RNA polymerase C (III) promotes the transcription of tRNA and 5S RNA genes. In S. cerevisiae, the enzyme is composed of 15 subunits, ranging from 10kDa to about 160kDa [
]. This region is probably a DNA-binding helix-turn-helix. |
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| Protein Domain |
| Name: |
RNA polymerase III Rpc82, C -terminal |
| Type: |
Domain |
| Description: |
DNA-directed RNA polymerases
(also known as DNA-dependent RNA polymerases) are responsible for the polymerisation of ribonucleotides into a sequence complementary to the template DNA. In eukaryotes, there are three different forms of DNA-directed RNA polymerases transcribing different sets of genes. Most RNA polymerases are multimeric
enzymes and are composed of a variable number of subunits. The core RNA polymerase complex consists of five subunits (two alpha, one beta, one beta-prime and one omega) and is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme []. The core RNA polymerase complex forms a "crab claw"-like structure with an internal channel running along the full length [
]. The key functional sites of the enzyme, as defined by mutational and cross-linking analysis, are located on the inner wall of this channel.RNA synthesis follows after the attachment of RNA polymerase to a specific site, the promoter, on the template DNA strand. The RNA synthesis process continues until a termination sequence is reached. The RNA product, which is synthesised in the 5' to 3' direction, is known as the primary transcript.
Eukaryotic nuclei contain three distinct types of RNA polymerases that differ in the RNA they synthesise:RNA polymerase I: located in the nucleoli, synthesises precursors of most ribosomal RNAs.RNA polymerase II: occurs in the nucleoplasm, synthesises mRNA precursors. RNA polymerase III: also occurs in the nucleoplasm, synthesises the precursors of 5S ribosomal RNA, the tRNAs, and a variety of other small nuclear and cytosolic RNAs. Eukaryotic cells are also known to contain separate mitochondrial and chloroplast RNA polymerases. Eukaryotic RNA polymerases, whose molecular masses vary in size from 500 to 700kDa, contain two non-identical large (>100kDa) subunits and an array of up to 12 different small (less than 50kDa) subunits.This entry describes the C-terminal region of several DNA-directed RNA polymerase III polypeptides which are related to the Saccharomyces cerevisiae RPC82 protein. RNA polymerase C (III) promotes the transcription of tRNA and 5S RNA genes. In Saccharomyces cerevisiae, the enzyme is composed of 15 subunits, ranging from 160 to about 10kDa []. |
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| Protein Domain |
| Name: |
Pseudouridine synthase, RsuA/RluB/E/F, conserved site |
| Type: |
Conserved_site |
| Description: |
Pseudouridine synthases catalyse the isomerisation of uridine to pseudouridine (Psi) in a variety of RNA molecules, and may function as RNA chaperones. Pseudouridine is the most abundant modified nucleotide found in all cellular RNAs. There are four distinct families of pseudouridine synthases that share no global sequence similarity, but which do share the same fold of their catalytic domain(s) and uracil-binding site and are descended from a common molecular ancestor. The catalytic domain consists of two subdomains, each of which has an α+β structure that has some similarity to the ferredoxin-like fold (note: some pseudouridine synthases contain additional domains). The active site is the most conserved structural region of the superfamily and is located between the two homologous domains. These families are [
,
]:Pseudouridine synthase I, TruA.Pseudouridine synthase II, TruB, which contains and additional C-terminal PUA domain.Pseudouridine synthase RsuA. RluB, RluE and RluF are also part of this family.Pseudouridine synthase RluA. TruC, RluC and RluD belong to this family.Pseudouridine synthase TruD, which has a natural circular permutation in the catalytic domain, as well as an insertion of a family-specific α+β subdomain.This entry represents several different pseudouridine synthases from family 3, including: RsuA (acts on small ribosomal subunit), RluB, RluE and RluF (act on large ribosomal subunit). RsuA from Escherichia coli catalyses formation of pseudouridine at position 516 in 16S rRNA during assembly of the 30S ribosomal subunit [
,
]. RsuA consists of an N-terminal domain connected by an extended linker to the central and C-terminal domains. Uracil and UMP bind in a cleft between the central and C-terminal domains near the catalytic residue Asp 102. The N-terminal domain shows structural similarity to the ribosomal protein S4. Despite only 15% amino acid identity, the other two domains are structurally similar to those of the tRNA-specific psi-synthase TruA, including the position of the catalytic Asp. Our results suggest that all four families of pseudouridine synthases share the same fold of their catalytic domain(s) and uracil-binding site.RluB, RluE and RluF are homologous enzymes which each convert specific uridine bases in E. coli ribosomal 23S RNA to pseudouridine:RluB modifies uracil-2605.RluE modifies uracil-3457.RluF modifies uracil-2604 and to a lesser extent U-2605. |
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| Protein Domain |
| Name: |
Tyrosine-tRNA ligase |
| Type: |
Family |
| Description: |
Tyrosine-tRNA ligases (TyrRS; also known as Tyrosyl-tRNA synthetases) (
) are widely distributed, being found in archaea, bacteria and eukaryotes. TyrRS is a homodimer which attaches Tyr to the appropriate tRNA. TyrRS is a class I tRNA synthetases, so it aminoacylates the 2'-OH of the nucleotide at the 3' end of the tRNA. The core domain is based on the Rossman fold and is responsible for the ATP-dependent formation of the enzyme bound aminoacyl-adenylate. It contains the class I characteristic 'HIGH' and 'KMSKS' motifs, which are involved in ATP binding. Studies have shown that the 'KMSKS' motif plays a role in the initial binding of tRNA(Tyr) to tyrosine-tRNA ligase [].The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [].The class Ia aminoacyl-tRNA synthetases consist of the isoleucyl, methionyl, valyl, leucyl, cysteinyl, and arginyl-tRNA synthetases; the class Ib include the glutamyl and glutaminyl-tRNA synthetases, and the class Ic are the tyrosyl and tryptophanyl-tRNA synthetases [
]. |
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| Protein Domain |
| Name: |
RNA polymerase sigma-70 region 2 |
| Type: |
Domain |
| Description: |
The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme [
]. RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors [
,
]. The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors [
].Region 2 of sigma-70 is the most conserved region of the entire protein. All members of this class of sigma-factor contain region 2. The high conservation is due to region 2 containing both the -10 promoter recognition helix and the primary core RNA polymerase binding determinant. The core-binding helix, interacts with the clamp domain of the largest polymerase subunit, beta prime [
,
]. The aromatic residues of the recognition helix, found at the C terminus of this domain are thought to mediate strand separation, thereby allowing transcription initiation [,
]. |
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| Protein Domain |
| Name: |
RNA polymerase sigma factor, region 3/4-like |
| Type: |
Homologous_superfamily |
| Description: |
The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme [
]. RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors [
,
]. The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors [
].This entry represents regions 3 and 4 (or sigma3 and sigma4 domains) found in several sigma factors, often in conjunction with the sigma2 domain (
). Both regions 3 and 4 are present in Sigma70 [
], Sigma28 (FliA), and SigA [], while region4 is also found in SigmaF [] and RpoE. Regions 3 and 4 have a nucleotide-binding 3-helical core structure, consisting of a closed or partly open bundle with a right-handed twist. Some other nucleotide-binding proteins are thought to contain domains with a similar topology. |
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| Protein Domain |
| Name: |
Dynamin, GTPase region, conserved site |
| Type: |
Conserved_site |
| Description: |
The P-loop guanosine triphosphatases (GTPases) control a
multitude of biological processes, ranging from cell division, cell cycling,and signal transduction, to ribosome assembly and protein synthesis. GTPases
exert their control by interchanging between an inactive GDP-bound state andan active GTP-bound state, thereby acting as molecular switches. The common
denominator of GTPases is the highly conserved guanine nucleotide-binding (G)domain that is responsible for binding and hydrolysis of guanine nucleotides.Members of the dynamin GTPase family appear to be ubiquitous. They catalyse
diverse membrane remodelling events in endocytosis, cell division, and plastidmaintenance. Their functional versatility also extends to other core cellular
processes, such as maintenance of cell shape or centrosome cohesion. Membersof the dynamin family are characterised by their common structure and by
conserved sequences in the GTP-binding domain. The minimal distinguishingarchitectural features that are common to all dynamins and are distinct from
other GTPases are the structure of the large GTPase domain (~280 amino acids)and the presence of two additional domains: the middle domain and the GTPase
effector domain (GED), which are involved in oligomerisationand regulation of the GTPase activity. In many dynamin family members, the
basic set of domains is supplemented by targeting domains, such as:pleckstrin-homology (PH) domain, proline-rich domains
(PRDs), or by sequences that target dynamins to specific organelles, such asmitochondria and chloroplasts [
,
,
].The dynamin-type G domain consists of a central eight-stranded β-sheet
surrounded by seven alpha helices and two one-turn helices.It contains the five canonical guanine nucleotide binding motifs (G1-5). The
P-loop (G1) motif (GxxxxGKS/T) is also present in ATPases (Walker A motif) andfunctions as a coordinator of the phosphate groups of the bound nucleotide. A
conserved threonine in switch-I (G2) and the conserved residues DxxG ofswitch-II (G3) are involved in Mg(2+) binding and GTP hydrolysis. The
nucleotide binding affinity of dynamins is typically low, with specificity forGTP provided by the mostly conserved N/TKxD motif (G4). The G5 or G-cap motif
is involved in binding the ribose moiety [,
,
].This entry represents a conserved site in the dynamin-type G domain and is based on a highly conserved region downstream of the ATP/GTP-binding motif 'A' (P-loop). |
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| Protein Domain |
| Name: |
3-ketodihydrosphingosine reductase KDSR-like |
| Type: |
Family |
| Description: |
This entry represents a group of 3-ketodihydrosphingosine reductases, including KDSR from animals and Tsc10 from yeasts and plants. They catalyse the reduction of 3-ketodihydrosphingosine (KDS) to dihydrosphingosine (DHS) and are required for sphingolipid biosynthesis [,
,
].Proteins in this entry show strong conservation of the active site tetrad and glycine rich NAD-binding motif of the classical SDRs. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (α/β folding pattern with a central β-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyse a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing [
,
,
].Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction [,
,
]. |
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| Protein Domain |
| Name: |
GPCR family 3, gamma-aminobutyric acid receptor, type B1 |
| Type: |
Family |
| Description: |
GPCR family 3 receptors (also known as family C) are structurally similar to other GPCRs, but do not show any significant sequence similarity and thus represent a distinct group. Structurally they are composed of four elements; an N-terminal signal sequence; a large hydrophilic extracellular agonist-binding region containing several conserved cysteine residues which could be involved in disulphide bonds; a shorter region containing seven transmembrane domains; and a C-terminal cytoplasmic domain of variable length [
]. Family 3 members include the metabotropic glutamate receptors, the extracellular calcium-sensing receptors, the gamma-amino-butyric acid (GABA) type B receptors, and the vomeronasal type-2 receptors [,
,
,
]. As these receptors regulate many important physiological processes they are potentially promising targets for drug development.GABA is the principal inhibitory neurotransmitter in the brain, and signals through ionotropic (type A and type C) and metabotropic (type B) receptor systems. The type B receptors have been cloned, and photoaffinity labelling experiments suggest that they correspond to two highly conserved receptor forms in the vertebrate nervous system [
]. These receptors are involved in the fine tuning of inhibitory synaptic transmission []. Presynaptic receptors inhibit neurotransmitter release by down-regulating high-voltage activated calcium channels, while postsynaptic receptors decrease neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials []. The type B receptors negatively couple to adenylyl cyclase and show sequence similarity to the metabotropic receptors for the excitatory neurotransmitter L-glutamate. The physiological form of the B receptor may be a heterodimer of the B1 and B2 subtypes []. Neurophysiological and pharmacological studies point to a major role of the
GABA type B receptor in the epileptogenesis of absence seizures []. Using in situ hybridisation, the gene encoding the human GABA type B1 receptor has been mapped to chromosome 6p21.3, in the vicinity of a susceptibility locus (EJM1) for idiopathic generalised epilepsies, identifying a candidate gene for inherited forms of epilepsy [,
].The metabotropic glutamate receptor-like protein E from Dictyostelium discoideum, which is probably a receptor for GABA and glutamate, is also included in this entry [
]. |
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| Protein Domain |
| Name: |
Signal transduction response regulator, predicted, VieB |
| Type: |
Family |
| 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 [
,
].This entry represents VieB-type response regulators. In Vibrio, it is part of a signal transduction pathway involved in cholera toxin production [
,
].Response regulators of the microbial two-component signal transduction systems typically consist of an N-terminal CheY-like receiver (phosphoacceptor) domain and a C-terminal output (usually DNA-binding) domain. In response to an environmental stimulus, a phosphoryl group is transferred from the His residue of sensor histidine kinase to an Asp residue in the CheY-like receiver domain of the cognate response regulator [
,
,
]. Phosphorylation of the receiver domain induces conformational changes that activate an associated output domain, which in turn triggers the response. Phosphorylation-induced conformational changes in response regulator molecules have been demonstrated in direct structural studies [].The output domain found in this group is so far unique. In part, it contains a divergent version of TPR repeats. |
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| Protein Domain |
| Name: |
Signal transduction response regulator with modified HD-GYP domain, putative |
| Type: |
Family |
| Description: |
This entry represents a group of signal transduction response regulators which contain a modified version of the HD-GYP domain as an output domain.Response regulators of the microbial two-component signal transduction systems typically consist of an N-terminal CheY-like receiver (phosphoacceptor) domain and a C-terminal output (usually DNA-binding) domain. In response to an environmental stimulus, a phosphoryl group is transferred from the His residue of sensor histidine kinase to an Asp residue in the CheY-like receiver domain of the cognate response regulator [
,
,
]. Phosphorylation of the receiver domain induces conformational changes that activate an associated output domain, which in turn triggers the response. Phosphorylation-induced conformational changes in response regulator molecule have been demonstrated in direct structural studies [].HD-GYP is a conserved domain found in response regulator modules of various signal transduction systems. The involvement of the HD-GYP domain in signal transduction was originally proposed on the basis of its association with CheY-like and other signal transduction domains [
] and was later directly demonstrated experimentally by showing that RpfG is involved in regulation of the biosynthesis of extracellular endoglucanase and polysaccharide [].A modification of the HD-GYP domain, which is found in this group,
, and several smaller groups, lacks the conserved distal portion of the domain and has certain substitutions in the characteristic metal-binding residues [
] of the HD superfamily phosphohydrolases, which likely render it catalytically inactive. Note that the prototypical HD domain () is not recognised in many members of this group.
The exact mode of action and targets of the HD-GYP output domain are not known [
]. HD-GYP proteins are associated to the HD domain superfamily of metal-dependent phosphohydrolases; HD designates the principal conserved residues implicated in metal binding and catalysis []. The HD-GYP version of the HD-type domain has many additional highly conserved residues, including a conserved GYP motif, hence its name [,
].It has been noted that the highly conserved sequence of the HD-GYP domain suggests high substrate specificity [
]. On the basis of its association with the GGDEF diguanylate cyclase domain, it has been also predicted that the HD-GYP domain may be involved in the metabolism of cyclic diguanylate or in dephosphorylation of some phosphotransfer domain []. |
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| Protein Domain |
| Name: |
Lysine-tRNA ligase |
| Type: |
Family |
| Description: |
Lysine-tRNA ligase (also known as Lysyl-tRNA synthetase) (
) is an alpha 2 homodimer that belong to both class I and class II. In eubacteria and eukaryota lysine-tRNA ligases belong to class II in the same family as aspartyl tRNA ligase. The class Ic lysine-tRNA ligase family is present in archaea and in a number of bacterial groups that include the alphaproteobacteria and spirochaetes[
]. A refined crystal structures shows that the active site of LysU is shaped to position the substrates for the nucleophilic attack of the lysine carboxylate on the ATP alpha-phosphate. No residues are directly involved in catalysis, but a number of highly conserved amino acids and three metal ions coordinate the substrates and stabilise the pentavalent transition state. A loop close to the catalytic pocket, disordered in the lysine-bound structure, becomes ordered upon adenine binding [].The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c []. |
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| Protein Domain |
| Name: |
Fungal ligninase, C-terminal |
| Type: |
Domain |
| Description: |
Peroxidases are haem-containing enzymes that use hydrogen peroxide as the electron acceptor to catalyse a number of oxidative reactions. Peroxidases are found in bacteria, fungi, plants and animals. Fungal ligninases are extracellular haem enzymes involved in the degradation of lignin. They include lignin peroxidases (LiPs), manganese-dependent peroxidases (MnPs) and versatile peroxidases, which combine the substrate-specificity characteristics of the other two [
]. In MnP, Mn2+serves as the reducing substrate [
].It is commonly thought that the plant polymer lignin is the second most abundant organic compound on Earth, exceeded only by cellulose. Higher plants synthesise vast quantities of insoluble macromolecules, including lignins. Lignin is an amorphous three-dimensional aromatic biopolymer composed of oxyphenylpropane units. Biodegradation of lignins is slow - it is probable that their decomposition is the rate-limiting step in the biospheric carbon-oxygen cycle, which is mediated almost entirely by the catabolic activities of microorganisms. The white-rot fungi are able extensively to decompose all the important structural components of wood, including both cellulose and lignin. Under the proper environmental conditions, white-rot fungi completely degrade all structural components of lignin, with ultimate formation of CO
2and H
2O. The first step in lignin degradation is depolymerisation, catalysed by the LiPs (ligninases). LiPs are secreted, along with hydrogen peroxide (H
2O
2), by white-rot fungi under conditions of nutrient limitation. The enzymes are not only important in lignin biodegradation, but are also potentially valuable in chemical waste disposal because of their ability to degrade environmental pollutants [
].To date, 3D structures have been determined for LiP [
] and MnP [] from Phanerochaete chrysosporium (White-rot fungus), and for the fungal peroxidase from Arthromyces ramosus [
]. All these proteins share the same architecture and consist of 2 all-alpha domains, between which is embedded the haem group. The helical topography of LiPs is nearly identical to that of yeast cytochrome c peroxidase (CCP) [], despite the former having four disulphide bonds, which are absent in CCP (MnP has an additional disulphide bond at the C terminus).This C-terminal domain is found in fungal ligninases. It is about 80 amino acids in length and forms an extended structure on the surface of the peroxidase domain
.
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| Protein Domain |
| Name: |
Pseudouridine synthase, RsuA/RluB/E/F |
| Type: |
Family |
| Description: |
Pseudouridine synthases catalyse the isomerisation of uridine to pseudouridine (Psi) in a variety of RNA molecules, and may function as RNA chaperones. Pseudouridine is the most abundant modified nucleotide found in all cellular RNAs. There are four distinct families of pseudouridine synthases that share no global sequence similarity, but which do share the same fold of their catalytic domain(s) and uracil-binding site and are descended from a common molecular ancestor. The catalytic domain consists of two subdomains, each of which has an α+β structure that has some similarity to the ferredoxin-like fold (note: some pseudouridine synthases contain additional domains). The active site is the most conserved structural region of the superfamily and is located between the two homologous domains. These families are [
,
]:Pseudouridine synthase I, TruA.Pseudouridine synthase II, TruB, which contains and additional C-terminal PUA domain.Pseudouridine synthase RsuA. RluB, RluE and RluF are also part of this family.Pseudouridine synthase RluA. TruC, RluC and RluD belong to this family.Pseudouridine synthase TruD, which has a natural circular permutation in the catalytic domain, as well as an insertion of a family-specific α+β subdomain.This entry represents several different pseudouridine synthases from family 3, including: RsuA (acts on small ribosomal subunit), RluB, RluE and RluF (act on large ribosomal subunit). RsuA from Escherichia coli catalyses formation of pseudouridine at position 516 in 16S rRNA during assembly of the 30S ribosomal subunit [
,
]. RsuA consists of an N-terminal domain connected by an extended linker to the central and C-terminal domains. Uracil and UMP bind in a cleft between the central and C-terminal domains near the catalytic residue Asp 102. The N-terminal domain shows structural similarity to the ribosomal protein S4. Despite only 15% amino acid identity, the other two domains are structurally similar to those of the tRNA-specific psi-synthase TruA, including the position of the catalytic Asp. Our results suggest that all four families of pseudouridine synthases share the same fold of their catalytic domain(s) and uracil-binding site.RluB, RluE and RluF are homologous enzymes which each convert specific uridine bases in E. coli ribosomal 23S RNA to pseudouridine:RluB modifies uracil-2605.RluE modifies uracil-3457.RluF modifies uracil-2604 and to a lesser extent U-2605. |
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| Protein Domain |
| Name: |
N-acetyl-gamma-glutamyl-phosphate reductase, type 2 |
| Type: |
Family |
| Description: |
N -Acetylglutamate (NAG) fulfils distinct biological roles in lower and higher organisms. In prokaryotes, lower eukaryotes and plants it is the first intermediate in the biosynthesis of arginine, whereas in ureotelic (excreting nitrogen mostly in the form of urea) vertebrates, it is an essential allosteric cofactor for carbamyl phosphate synthetase I (CPSI), the first enzyme of the urea cycle. The pathway that leads from glutamate to arginine in lower organisms employs eight steps, starting with the acetylation of glutamate to form NAG. In these species, NAG can be produced by two enzymatic reactions: one catalysed by NAG synthase (NAGS) and the other by ornithine acetyltransferase (OAT). In ureotelic species, NAG is produced exclusively by NAGS. In lower organisms, NAGS is feedback-inhibited by L-arginine, whereas mammalian NAGS activity is significantly enhanced by this amino acid. The NAGS genes of bacteria, fungi and mammals are more diverse than other arginine-biosynthesis and urea-cycle genes. The evolutionary relationship between the distinctly different roles of NAG and its metabolism in lower and higher organisms remains to be determined [
].The pathway from glutamate to arginine is: NAGS; N-acetylglutamate synthase (
) (glutamate to N-acetylglutamate)
NAGK; N-acetylglutamate kinase (
) (N-acetylglutamate to N-acetylglutamate-5P)
N-acetyl-gamma-glutamyl-phosphate reductase (
) (N-acetylglutamate-5P to N-acetylglumate semialdehyde)
Acetylornithine aminotransferase (
) (N-acetylglumate semialdehyde to N-acetylornithine)
Acetylornithine deacetylase (
) (N-acetylornithine to ornithine)
Arginase (
) (ornithine to arginine)
N-acetyl-gamma-glutamyl-phosphate reductase (
) (AGPR, NAGSA dehydrogenase) [
,
] is the enzyme that catalyses the third step in the biosynthesis of arginine from glutamate, the NADP-dependent reduction of N-acetyl-5-glutamyl phosphate into N-acetylglutamate 5-semialdehyde. In bacteria it is a monofunctional protein of 35 to 38kDa (gene argC), while in fungi it is part of a bifunctional mitochondrial enzyme (gene ARG5,6, arg11 or arg-6) which contains a N-terminal acetylglutamate kinase () domain and a C-terminal AGPR domain. In the Escherichia coli enzyme, a cysteine has been shown to be implicated in the catalytic activity, and the region around this residue is well conserved.
This entry represents the less common of two related families of N-acetyl-gamma-glutamyl-phosphate reductase, an enzyme catalyzing the third step or Arg biosynthesis from Glu. The two families differ by phylogeny, similarity clustering, and gap architecture in a multiple sequence alignment. |
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| Protein Domain |
| Name: |
ATP phosphoribosyltransferase HisG, short form |
| Type: |
Family |
| Description: |
ATP phosphoribosyltransferase (
) is the enzyme that catalyzes the first step in the biosynthesis of histidine in bacteria, fungi and plants as shown below. It is a member of the larger phosphoribosyltransferase superfamily of enzymes which catalyse the condensation of 5-phospho-alpha-D-ribose 1-diphosphate with nitrogenous bases in the presence of divalent metal ions [
].ATP + 5-phospho-alpha-D-ribose 1-diphosphate = 1-(5-phospho-D-ribosyl)-ATP + diphosphate Histidine biosynthesis is an energetically expensive process and ATP phosphoribosyltransferase activity is subject to control at several levels. Transcriptional regulation is based primarily on nutrient conditions and determines the amount of enzyme present in the cell, while feedback inihibition rapidly modulates activity in response to cellular conditions. The enzyme has been shown to be inhibited by 1-(5-phospho-D-ribosyl)-ATP, histidine, ppGpp (a signal associated with adverse environmental conditions) and ADP and AMP (which reflect the overall energy status of the cell). As this pathway of histidine biosynthesis is present only in prokayrotes, plants and fungi, this enzyme is a promising target for the development of novel antimicrobial compounds and herbicides.The ATP phosphoribosyltransferase come in two forms: a long form containing two catalytic domains and a C-terminal regulatory domain, and a short form in which the regulatory domain is missing. The long form is catalytically competent, but in organisms with the short form, a histidyl-tRNA synthetase paralogue, HisZ, is required for enzyme activity [
].The structures of the long form enzymes from Escherichia coli (
) and Mycobacterium tuberculosis (
) have been determined [
,
]. The enzyme itself exists in equilibrium between an active dimeric form, an inactive hexameric form and higher aggregates. Interconversion between the various forms is largely reversible and is influenced by the binding of the natural substrates and inhibitors of the enzyme. The two catalytic domains are linked by a two-stranded β-sheet and togther form a "periplamsic binding protein fold". A crevice between these domains contains the active site. The C-terminal domain is not directly involved in catalysis but appears to be involved the formation of hexamers, induced by the binding of inhibitors such as histidine to the enzyme, thus regulating activity.
This entry represents the short form ATP phosphoribosyltransferases. |
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| Protein Domain |
| Name: |
P2X6 purinoceptor |
| Type: |
Family |
| Description: |
P2X purinoceptors are cell membrane ion channels, gated by adenosine 5'-triphosphate (ATP) and other nucleotides; they have been found to be widely expressed on mammalian cells, and, by means of their functional properties, can be differentiated into three sub-groups. The first group is almost equally well activated by ATP and its analogue alpha,betamethylene-ATP, whereas, the second group is not activated by the latter compound. A third type of receptor (also called P2Z) is distinguished by the fact that repeated or prolonged agonist application leads to the opening of much larger pores, allowing large molecules to traverse the cell membrane. This increased permeability rapidly leads to cell death, and lysis.Molecular cloning studies have identified seven P2X receptor subtypes, designated P2XR1-P2XR7, however, P2X1R, P2X2R, P2X3R, P2X4R, and P2X7R are functional [
]. These receptors are proteins that share 35-48% amino acid identity, and possess two putative transmembrane (TM) domains, separated by a long (~270 residues) intervening sequence, which is thought to form an extracellular loop. Around 1/4 of the residues within the loop are invariant between the cloned subtypes, including 10 characteristic cysteines.Studies of the functional properties of heterologously expressed P2X receptors, together with the examination of their distribution in native tissues, suggests they likely occur as both homo- and hetero multimers in vivo [
,
]. Stimulation of these receptors induces changes in intracellular ion homeostasis leading to multiple key responses crucial for initiation, propagation, and resolution of inflammation []. The P2X7 subtype has an important role in the activation of lymphocyte, granulocyte, macrophage and dendritic cell responses and, therefor, it may be a promising target for anti-inflammatory therapies.The P2X6 receptor (along with P2X2, P2X4 and P2X5) falls into a group of receptors that are sensitive to ATP, but not alphabetamethyleneATP. There is some evidence that P2X6 may heteropolymerise with P2X4, since they are often found together in native tissues, and can be co-immunoprecipitated. P2X6 and P2X4 receptors are present in the gastrointestinal tract, being involved in synaptic transmission, taste sensation, and pain, among other functions. P2XR6 is present in capillary vessels in the proximal region of the gut and to a lesser extent in the distal region [
]. |
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| Protein Domain |
| Name: |
Ecdysteroid receptor |
| Type: |
Family |
| Description: |
Steroid or nuclear hormone receptors (NRs) constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis. Members of the superfamily include the steroid hormone receptors and receptors for thyroid hormone, retinoids, 1,25-dihydroxy-vitamin D3 and a variety of other ligands [
]. The proteins function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner [,
]. In addition to C-terminal ligand-binding domains, these nuclear receptors contain a highly-conserved, N-terminal zinc-finger that mediates specific binding to target DNA sequences, termed ligand-responsive elements. In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity.NRs are extremely important in medical research, a large number of them being implicated in diseases such as cancer, diabetes, hormone resistance syndromes, etc. While several NRs act as ligand-inducible transcription factors, many do not yet have a defined ligand and are accordingly termed 'orphan' receptors. During the last decade, more than 300 NRs have been described, many of which are orphans, which cannot easily be named due to current nomenclature confusions in the literature. However, a new system has recently been introduced in an attempt to rationalise the increasingly complex set of names used to describe superfamily members.In Drosophila melanogaster, the steroid hormone ecdysone triggers larval-to-
adult metamorphosis, a process in which the hormone induces imaginal tissuesto generate adult structures, and larval tissues to degenerate [
]. Theecdysone receptor (EcR) binds DNA with high specificity at ecdysone response
elements. EcR is nuclear and is found in larval wing discs, pupal wings andin prothoracic glands.
In the mosquito Aedes aegypti, 20-hydroxyecdysone plays an important role
in the regulation of egg maturation []. There are three EcR transcripts(of 4.2kb, 6kb and 11kb) in adult mosquitoes; 4.2kb mRNA is predominantly expressed in female mosquitoes during vitellogenesis. In both the fat body and ovaries of the female mosquito, the level of EcR mRNA is high at the previtellogenic period and after the onset of vitellogenesis []. Synonym(s): 1H nuclear receptor |
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| Protein Domain |
| Name: |
Methioninyl-tRNA synthetase core domain |
| Type: |
Domain |
| Description: |
The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [].Methionine tRNA synthetase (MetRS, also known as methionine tRNA ligase), a class I aminoacyl-tRNA synthetases, aminoacylates the 2'-OH of the nucleotide at the 3' of the appropriate tRNA. MetRS, which consists of the core domain and an anti-codon binding domain, functions as a monomer. However, in some species the anti-codon binding domain is followed by an EMAP domain. In this case, MetRS functions as a homodimer. The core domain is based on the Rossman fold and is responsible for the ATP-dependent formation of the enzyme bound aminoacyl-adenylate. It contains the characteristic class I 'HIGH' and 'KMSKS' motifs, which are involved in ATP binding. As a result of a deletion event, MetRS has a significantly shorter core domain insertion than IleRS, ValRS, and LeuR. Consequently, the MetRS insertion lacks the editing function [
].This entry represents the catalytic core domain of MetRS. |
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| Protein Domain |
| Name: |
Integrin beta-2 superfamily |
| Type: |
Homologous_superfamily |
| Description: |
Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton and activate many intracellular signalling pathways [
,
]. An integrin receptor is a heterodimer composed of alpha and beta subunits. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a vWA domain inserted within the integrin domain at the N terminus.Most integrins recognise relatively short peptide motifs, and in general require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits [
]. There are at least 18 types of alpha and 8 types of beta subunits recognised in humans []. Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule []. Each association of alpha and beta subunits has its own binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activate or inhibit another.Integrin Beta-2 is also referred to as ITGB2 and is known to interact with three different alpha integrin chains: ITGAL, ITGAM and ITGAX. These three integrin heterodimers are associated with leukocyte adhesion deficiency (LAD), which is characterised by recurrent bacterial infections. LFA-1 (ITGB2/ITGAL) is one of the most well studied of these integrins. Engagement of LFA-1 results in increased AP-1 dependent gene expression, which is mediated by the nuclear translocation of JAB1 []. The ligand for LFA-1 is JAM-1, a member of the endothelial immunoglobulin superfamily. JAM-1 contributes to LFA-1 dependent transendothelial migration of leukocytes and LFA-1 mediated arrest of T cells []. Studies of marginal zone (MZ) B cells also showed that LFA-1, together with alpha4beta1, is required for localisation of those cells in the splenic MZ and that these integrins are necessary for lymphoid tissue compartmentalization []. |
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| Protein Domain |
| Name: |
DNA topoisomerase I, zinc ribbon-like, bacterial-type |
| Type: |
Domain |
| Description: |
DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single- or double-strand breaks, crossing the strands through one another, then resealing the breaks [
]. These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis [,
]. DNA topoisomerases are divided into two classes: type I enzymes (; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (
; topoisomerases II, IV and VI) break double-strand DNA [
].Type I topoisomerases are ATP-independent enzymes (except for reverse gyrase), and can be subdivided according to their structure and reaction mechanisms: type IA (Topo IA; bacterial and archaeal topoisomerase I, topoisomerase III and reverse gyrase) and type IB (Topo IB; eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA. This function is vital for the processes of replication, transcription, and recombination. Unlike Topo IA enzymes, Topo IB enzymes do not require a single-stranded region of DNA or metal ions for their function. The type IB family of DNA topoisomerases includes eukaryotic nuclear topoisomerase I, topoisomerases of poxviruses, and bacterial versions of Topo IB [
]. They belong to the superfamily of DNA breaking-rejoining enzymes, which share the same fold in their C-terminal catalytic domain and the overall reaction mechanism with tyrosine recombinases [,
]. The C-terminal catalytic domain in topoisomerases is linked to a divergent N-terminal domain that shows no sequence or structure similarity to the N-terminal domains of tyrosine recombinases [,
].This entry represents the C-terminal zinc-ribbon-like domain found in bacterial topoisomerase I (type IA) enzymes. Escherichia coli topoisomerase I proteins contain five copies of a zinc-ribbon-like domain at their C terminus, two of which have lost their cysteine residues and are therefore probably not able to bind zinc [
]. This domain is still considered to be a member of the zinc-ribbon superfamily despite not being able to bind zinc. |
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| Protein Domain |
| Name: |
ATP phosphoribosyltransferase, catalytic domain |
| Type: |
Domain |
| Description: |
ATP phosphoribosyltransferase (
) is the enzyme that catalyzes the first step in the biosynthesis of histidine in bacteria, fungi and plants as shown below. It is a member of the larger phosphoribosyltransferase superfamily of enzymes which catalyse the condensation of 5-phospho-alpha-D-ribose 1-diphosphate with nitrogenous bases in the presence of divalent metal ions [
].ATP + 5-phospho-alpha-D-ribose 1-diphosphate = 1-(5-phospho-D-ribosyl)-ATP + diphosphate Histidine biosynthesis is an energetically expensive process and ATP phosphoribosyltransferase activity is subject to control at several levels. Transcriptional regulation is based primarily on nutrient conditions and determines the amount of enzyme present in the cell, while feedback inihibition rapidly modulates activity in response to cellular conditions. The enzyme has been shown to be inhibited by 1-(5-phospho-D-ribosyl)-ATP, histidine, ppGpp (a signal associated with adverse environmental conditions) and ADP and AMP (which reflect the overall energy status of the cell). As this pathway of histidine biosynthesis is present only in prokayrotes, plants and fungi, this enzyme is a promising target for the development of novel antimicrobial compounds and herbicides.ATP phosphoribosyltransferase is found in two distinct forms: a long form containing two catalytic domains and a C-terminal regulatory domain, and a short form in which the regulatory domain is missing. The long form is catalytically competent, but in organisms with the short form, a histidyl-tRNA synthetase paralogue, HisZ, is required for enzyme activity [
].This entry represents the catalytic region of this enzyme.
The structures of the long form enzymes from Escherichia coli (
) and Mycobacterium tuberculosis (
) have been determined [
,
]. The enzyme itself exists in equilibrium between an active dimeric form, an inactive hexameric form and higher aggregates. Interconversion between the various forms is largely reversible and is influenced by the binding of the natural substrates and inhibitors of the enzyme. The two catalytic domains are linked by a two-stranded β-sheet and togther form a "periplasmic binding protein fold". A crevice between these domains contains the active site. The C-terminal domain is not directly involved in catalysis but appears to be involved the formation of hexamers, induced by the binding of inhibitors such as histidine to the enzyme, thus regulating activity.
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| Protein Domain |
| Name: |
ATP phosphoribosyltransferase HisG |
| Type: |
Family |
| Description: |
ATP phosphoribosyltransferase (
) is the enzyme that catalyzes the first step in the biosynthesis of histidine in bacteria, fungi and plants as shown below. It is a member of the larger phosphoribosyltransferase superfamily of enzymes which catalyse the condensation of 5-phospho-alpha-D-ribose 1-diphosphate with nitrogenous bases in the presence of divalent metal ions [
].ATP + 5-phospho-alpha-D-ribose 1-diphosphate = 1-(5-phospho-D-ribosyl)-ATP + diphosphate Histidine biosynthesis is an energetically expensive process and ATP phosphoribosyltransferase activity is subject to control at several levels. Transcriptional regulation is based primarily on nutrient conditions and determines the amount of enzyme present in the cell, while feedback inihibition rapidly modulates activity in response to cellular conditions. The enzyme has been shown to be inhibited by 1-(5-phospho-D-ribosyl)-ATP, histidine, ppGpp (a signal associated with adverse environmental conditions) and ADP and AMP (which reflect the overall energy status of the cell). As this pathway of histidine biosynthesis is present only in prokayrotes, plants and fungi, this enzyme is a promising target for the development of novel antimicrobial compounds and herbicides.The ATP phosphoribosyltransferase come in two forms: a long form containing two catalytic domains and a C-terminal regulatory domain, and a short form in which the regulatory domain is missing. The long form is catalytically competent, but in organisms with the short form, a histidyl-tRNA synthetase paralogue, HisZ, is required for enzyme activity [
].The structures of the long form enzymes from Escherichia coli (
) and Mycobacterium tuberculosis (
) have been determined [
,
]. The enzyme itself exists in equilibrium between an active dimeric form, an inactive hexameric form and higher aggregates. Interconversion between the various forms is largely reversible and is influenced by the binding of the natural substrates and inhibitors of the enzyme. The two catalytic domains are linked by a two-stranded β-sheet and togther form a "periplamsic binding protein fold". A crevice between these domains contains the active site. The C-terminal domain is not directly involved in catalysis but appears to be involved the formation of hexamers, induced by the binding of inhibitors such as histidine to the enzyme, thus regulating activity.
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| Protein Domain |
| Name: |
ATP phosphoribosyltransferase HisG, long form |
| Type: |
Family |
| Description: |
ATP phosphoribosyltransferase (
) is the enzyme that catalyzes the first step in the biosynthesis of histidine in bacteria, fungi and plants as shown below. It is a member of the larger phosphoribosyltransferase superfamily of enzymes which catalyse the condensation of 5-phospho-alpha-D-ribose 1-diphosphate with nitrogenous bases in the presence of divalent metal ions [
].ATP + 5-phospho-alpha-D-ribose 1-diphosphate = 1-(5-phospho-D-ribosyl)-ATP + diphosphate Histidine biosynthesis is an energetically expensive process and ATP phosphoribosyltransferase activity is subject to control at several levels. Transcriptional regulation is based primarily on nutrient conditions and determines the amount of enzyme present in the cell, while feedback inihibition rapidly modulates activity in response to cellular conditions. The enzyme has been shown to be inhibited by 1-(5-phospho-D-ribosyl)-ATP, histidine, ppGpp (a signal associated with adverse environmental conditions) and ADP and AMP (which reflect the overall energy status of the cell). As this pathway of histidine biosynthesis is present only in prokayrotes, plants and fungi, this enzyme is a promising target for the development of novel antimicrobial compounds and herbicides.The ATP phosphoribosyltransferase come in two forms: a long form containing two catalytic domains and a C-terminal regulatory domain, and a short form in which the regulatory domain is missing. The long form is catalytically competent, but in organisms with the short form, a histidyl-tRNA synthetase paralogue, HisZ, is required for enzyme activity [
].The structures of the long form enzymes from Escherichia coli (
) and Mycobacterium tuberculosis (
) have been determined [
,
]. The enzyme itself exists in equilibrium between an active dimeric form, an inactive hexameric form and higher aggregates. Interconversion between the various forms is largely reversible and is influenced by the binding of the natural substrates and inhibitors of the enzyme. The two catalytic domains are linked by a two-stranded β-sheet and togther form a "periplamsic binding protein fold". A crevice between these domains contains the active site. The C-terminal domain is not directly involved in catalysis but appears to be involved the formation of hexamers, induced by the binding of inhibitors such as histidine to the enzyme, thus regulating activity.
This entry represents the long form ATP phosphoribosyltransferase. |
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| Protein Domain |
| Name: |
ATP phosphoribosyltransferase, conserved site |
| Type: |
Conserved_site |
| Description: |
ATP phosphoribosyltransferase (
) is the enzyme that catalyzes the first step in the biosynthesis of histidine in bacteria, fungi and plants as shown below. It is a member of the larger phosphoribosyltransferase superfamily of enzymes which catalyse the condensation of 5-phospho-alpha-D-ribose 1-diphosphate with nitrogenous bases in the presence of divalent metal ions [
].ATP + 5-phospho-alpha-D-ribose 1-diphosphate = 1-(5-phospho-D-ribosyl)-ATP + diphosphate Histidine biosynthesis is an energetically expensive process and ATP phosphoribosyltransferase activity is subject to control at several levels. Transcriptional regulation is based primarily on nutrient conditions and determines the amount of enzyme present in the cell, while feedback inihibition rapidly modulates activity in response to cellular conditions. The enzyme has been shown to be inhibited by 1-(5-phospho-D-ribosyl)-ATP, histidine, ppGpp (a signal associated with adverse environmental conditions) and ADP and AMP (which reflect the overall energy status of the cell). As this pathway of histidine biosynthesis is present only in prokayrotes, plants and fungi, this enzyme is a promising target for the development of novel antimicrobial compounds and herbicides.ATP phosphoribosyltransferase is found in two distinct forms: a long form containing two catalytic domains and a C-terminal regulatory domain, and a short form in which the regulatory domain is missing. The long form is catalytically competent, but in organisms with the short form, a histidyl-tRNA synthetase paralogue, HisZ, is required for enzyme activity [
].This entry represents the catalytic region of this enzyme.
The structures of the long form enzymes from Escherichia coli (
) and Mycobacterium tuberculosis (
) have been determined [
,
]. The enzyme itself exists in equilibrium between an active dimeric form, an inactive hexameric form and higher aggregates. Interconversion between the various forms is largely reversible and is influenced by the binding of the natural substrates and inhibitors of the enzyme. The two catalytic domains are linked by a two-stranded β-sheet and togther form a "periplasmic binding protein fold". A crevice between these domains contains the active site. The C-terminal domain is not directly involved in catalysis but appears to be involved the formation of hexamers, induced by the binding of inhibitors such as histidine to the enzyme, thus regulating activity.
This entry represents the conserved site of ATP phosphoribosyltransferase enzymes. |
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| Protein Domain |
| Name: |
Response regulator B-type, plant |
| Type: |
Family |
| Description: |
Members of this group are plant response regulators of the B type. B-type plant response regulators most closely resemble the classical microbial response regulators.Classical two-component signal transduction systems--consisting of a histidine protein kinase (HK) to sense signal input and a response regulator (RR) to mediate output--are widespread in prokaryotes. Their counterparts are also found in eukaryotes, indicating that they represent an ancient and evolutionarily conserved signalling mechanism. In plants, two-component systems are involved in phytohormone, stress, and light signalling [
,
]. Plant response regulators (called ARRs in Arabidopsis thaliana (Mouse-ear cress)) fall into three distinct families based on domain architecture: A-type RRs are stand-alone receiver domains; B-type RRs contain an N-terminal receiver domain fused to a Myb-like DNA-binding domain and a variable C-terminal domain; pseudo-response regulators contain an atypical receiver domain.
The classical microbial RRs consist of an N-terminal CheY-like receiver (phosphoacceptor) domain and a C-terminal output (usually DNA-binding) domain. In a typical microbial signal transduction system, in response to an environmental stimulus, a phosphoryl group is transferred from the His residue of sensor histidine kinase to an Asp residue in the CheY-like receiver domain of the cognate response regulator [
,
,
]. Phosphorylation of the receiver domain induces conformational changes that activate an associated output domain, which in turn triggers the response. Phosphorylation-induced conformational changes in response regulator molecules have been demonstrated in direct structural studies [].The output domain of B-type plant RRs is a central Myb-like DNA-binding domain (with the B, or GARP, motif) [
,
,
] which is not found in two-component prokaryotic systems. This domain is believed to be responsible for the promoter-binding and transcription factor activity of the B-type plant RRs [,
]. The B motif contains a helix-turn-helix structure and a potential nuclear localization signal, and is considered to be a multifunctional domain responsible for both nuclear localization and DNA binding [].A variable C-terminal domain may also play a role as part of the output module and provides the basis for defining several small subgroups. The functions of these unique C-terminal domains and biological significance of the subgroups are unclear. |
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| Protein Domain |
| Name: |
Zinc finger, FPG/IleRS-type |
| Type: |
Domain |
| Description: |
This entry represents a zinc finger domain found at the C-terminal in both DNA glycosylase/AP lyase enzymes and in isoleucyl tRNA synthetase. In these two types of enzymes, the C-terminal domain forms a zinc finger. Some related proteins may not bind zinc.DNA glycosylase/AP lyase enzymes are involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. These enzymes have both DNA glycosylase activity (
) and AP lyase activity (
) [
]. Examples include formamidopyrimidine-DNA glycosylases (Fpg; MutM) and endonuclease VIII (Nei). Formamidopyrimidine-DNA glycosylases (Fpg, MutM) is a trifunctional DNA base excision repair enzyme that removes a wide range of oxidation-damaged bases (N-glycosylase activity; ) and cleaves both the 3'- and 5'-phosphodiester bonds of the resulting apurinic/apyrimidinic site (AP lyase activity;
). Fpg has a preference for oxidised purines, excising oxidized purine bases such as 7,8-dihydro-8-oxoguanine (8-oxoG). ITs AP (apurinic/apyrimidinic) lyase activity introduces nicks in the DNA strand, cleaving the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates. Fpg is a monomer composed of 2 domains connected by a flexible hinge [
]. The two DNA-binding motifs (a zinc finger and the helix-two-turns-helix motifs) suggest that the oxidized base is flipped out from double-stranded DNA in the binding mode and excised by a catalytic mechanism similar to that of bifunctional base excision repair enzymes []. Fpg binds one ion of zinc at the C terminus, which contains four conserved and essential cysteines []. Endonuclease VIII (Nei) has the same enzyme activities as Fpg above, but with a preference for oxidized pyrimidines, such as thymine glycol, 5,6-dihydrouracil and 5,6-dihydrothymine [,
]. An Fpg-type zinc finger is also found at the C terminus of isoleucyl tRNA synthetase (
) [
,
]. This enzyme catalyses the attachment of isoleucine to tRNA(Ile). As IleRS can inadvertently accommodate and process structurally similar amino acids such as valine, to avoid such errors it has two additional distinct tRNA(Ile)-dependent editing activities. One activity is designated as 'pre-transfer' editing and involves the hydrolysis of activated Val-AMP. The other activity is designated 'post-transfer' editing and involves deacylation of mischarged Val-tRNA(Ile) []. |
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| Protein Domain |
| Name: |
Memapsin-like |
| Type: |
Domain |
| Description: |
This entry includes the peptidase domain of aspartic endopeptidases known as memapsins. In humans there are two enzymes, memapsin-1 (also known as BACE2 or beta-site of APP cleaving enzyme 1; MEROPS identifier A01.041) and memapsin-2 (BACE1; MEROPS identifier A01.004).Beta-secretase is an aspartic-acid protease important in the pathogenesis of Alzheimer's disease, and in the formation of myelin sheaths in peripheral nerve cells. It cleaves amyloid precursor protein (APP) to reveal the N terminus of the beta-amyloid peptides. The beta-amyloid peptides are the major components of the amyloid plaques formed in the brain of patients with Alzheimer's disease (AD). Since BACE mediates one of the cleavages responsible for generation of AD, it is regarded as a potential target for pharmacological intervention in AD. Beta-secretase is a member of pepsin family of aspartic proteases (peptidase family A1) [
,
].Aspartyl proteases (APs), also known as acid proteases, ([intenz:3.4.23.-]) are a widely distributed family of proteolytic enzymes [,
,
,
,
,
] known to exist in vertebrates, fungi, plants, retroviruses and some plant viruses. APs use an Asp dyad to hydrolyze peptide bonds.APs found in eukaryotic cells are α/β monomers composed of two asymmetric lobes ("bilobed"). Each of the lobes provides a catalytic Asp residue, positioned within the hallmark motif Asp-Thr/Ser-Gly, to the active site. The N- and C-terminal domains, although structurally related by a 2-fold axis, have only limited sequence homology except the vicinity of the active site. This suggests that the enzymes evolved by an ancient duplication event. The enzymes specifically cleave bonds in peptides which have at least six residues in length with hydrophobic residues in both the P1 and P1' positions. The active site is located at the groove formed by the two lobes, with an extended loop projecting over the cleft to form an 11-residue flap, which encloses substrates and inhibitors in the active site. Specificity is determined by nearest-neighbour hydrophobic residues surrounding the catalytic aspartates, and by three residues in the flap. The enzymes are mostly secreted from cells as inactive proenzymes that activate autocatalytically at acidic pH. Eukaryotic APs form peptidase family A1 of clan AA. |
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| Protein Domain |
| Name: |
Aminoacyl-tRNA synthetase, class I, anticodon-binding |
| Type: |
Domain |
| Description: |
This entry represents the anticodon binding domain found at the C terminus of class I aminoacyl-tRNA synthetases (such as Glutamate-tRNA ligase) predominately in bacteria [
,
]. Glutamate-tRNA ligase catalyzes the attachment of glutamate to tRNA(Glu) in a two-step reaction: glutamate is first activated by ATP to form Glu-AMP and then transferred to the acceptor end of tRNA(Glu) [].The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [].Structurally, an α-helix-bundle anticodon-binding domain characterises the class Ia synthetases, whereas the class Ib synthetases, GlnRS and GluRS have distinct anticodon-binding domains. The anticodon-binding domain has a multi-helical structure, consisting of two all-alpha subdomains. The Rossmann-fold, made up of alternate α-helices and β-sheets involved in ATP binding in the extended conformation, and the anticodon-binding domains are connected by a beta-α-α-beta-alpha topology ('SC fold') domain that contains the class I specific KMSKS motif [
,
]. |
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| Protein Domain |
| Name: |
Transient receptor potential cation channel subfamily V member 4 |
| Type: |
Family |
| Description: |
Transient receptor potential (TRP) channels can be described as tetramers formed by subunits with six transmembrane domains and containing cation-selective pores, which in several cases show high calcium permeability. The molecular architecture of TRP channels is reminiscent of voltage-gated channels and comprises six putative transmembrane segments (S1-S6), intracellular N- and C-termini, and a pore-forming reentrant loop between S5 and S6 [
].TRP channels represent a superfamily conserved from worms to humans that comprise seven subfamilies [
]: TRPC (canonical), TRPV (vanilloid), TRPM (melastatin or long TRPs), TRPA (ankyrin, whose only member is Transient receptor potential cation channel subfamily A member 1, TrpA1), TRPP (polycystin), TRPML (mucolipin) and TRPN (Nomp-C homologues), which has a single member that can be found in worms, flies, and zebrafish. TRPs are classified essentially according to their primary amino acid sequence rather than selectivity or ligand affinity, due to their heterogeneous properties and complex regulation.TRP channels are involved in many physiological functions, ranging from pure sensory functions, such as pheromone signalling, taste transduction, nociception, and temperature sensation, over homeostatic functions, such as Ca2+ and Mg2+ reabsorption and osmoregulation, to many other motile functions, such as muscle contraction and vaso-motor control [].The TRPV (vanilloid) subfamily can be divided into two distinct groups. The first, which comprises TrpV1, TrpV2, TrpV3, and TrpV4, with nonselective cation conducting pores, has members which can be activated by temperature as well as chemical stimuli. They are involved in a range of functions including nociception, thermosensing and osmolarity sensing. The second group, which consists of TrpV5 and TrpV6, (also known as epithelial calcium channels 1 and 2), highly calcium selective, are involved in renal Ca2+ absorption/reabsorption [
,
].TrpV4 is a non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity. It is expressed at high levels in the kidney, liver, heart and central nervous system, and activated by extracellular hypo-osmoticity, leading to increased transcellular ion flux and paracellular permeability, which may allow the cells to adjust to changes in extracellular osmolarity [
,
,
]. TRPV4 is can also be activated chemically by metabolites of arachidonic acid and alpha-isomers of phorbol esters [], by heat [] and other factors []. This protein has been related to infectious diseases [] and other pathologies [,
]. |
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| Protein Domain |
| Name: |
Estrogen receptor/oestrogen-related receptor |
| Type: |
Family |
| Description: |
Steroid or nuclear hormone receptors (NRs) constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis. Members of the superfamily include the steroid hormone receptors and receptors for thyroid hormone, retinoids, 1,25-dihydroxy-vitamin D3 and a variety of other ligands [
]. The proteins function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner [,
]. In addition to C-terminal ligand-binding domains, these nuclear receptors contain a highly-conserved, N-terminal zinc-finger that mediates specific binding to target DNA sequences, termed ligand-responsive elements. In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity.NRs are extremely important in medical research, a large number of them being implicated in diseases such as cancer, diabetes, hormone resistance syndromes, etc. While several NRs act as ligand-inducible transcription factors, many do not yet have a defined ligand and are accordingly termed 'orphan' receptors. During the last decade, more than 300 NRs have been described, many of which are orphans, which cannot easily be named due to current nomenclature confusions in the literature. However, a new system has recently been introduced in an attempt to rationalise the increasingly complex set of names used to describe superfamily members.The oestrogen receptors (ERs) are steroid or nuclear hormone receptors that act as transcription regulators involved in diverse physiological functions. Oestrogen receptors function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner. The ER consists of three functional and structural domains: an N-terminal modulatory domain, a highly conserved DNA-binding domain that recognises specific sequences (
), and a C-terminal ligand-binding domain (
).
This entry represents oestrogen receptors and oestrogen-related receptors, which are members of the subfamily 3 of nuclear receptors [
]. Oestrogen-related receptors (ERR-alpha, ERR-beta, and ERR-gamma) are orphan nuclear receptors whose physiological ligands have not yet been identified. Although ERRs are closely related to oestrogen receptors(ERs) they do not respond to oestrogens [
]. |
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| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
1895
|
| Description: |
threonyl-tRNA synthetase, putative / threonine--tRNA ligase, putative; IPR002320 (Threonine-tRNA ligase, class IIa); GO:0000166 (nucleotide binding), GO:0004812 (aminoacyl-tRNA ligase activity), GO:0004829 (threonine-tRNA ligase activity), GO:0005524 (ATP binding), GO:0005737 (cytoplasm), GO:0006418 (tRNA aminoacylation for protein translation), GO:0006435 (threonyl-tRNA aminoacylation) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
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•
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•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
4135
|
| Description: |
disease resistance protein (TIR-NBS-LRR class), putative; IPR000157 (Toll/interleukin-1 receptor homology (TIR) domain), IPR000767 (Disease resistance protein), IPR001611 (Leucine-rich repeat), IPR027417 (P-loop containing nucleoside triphosphate hydrolase); GO:0005515 (protein binding), GO:0006952 (defense response), GO:0007165 (signal transduction), GO:0043531 (ADP binding) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
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•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
2085
|
| Description: |
Protein kinase family protein; IPR011009 (Protein kinase-like domain), IPR013320 (Concanavalin A-like lectin/glucanase, subgroup), IPR025287 (Wall-associated receptor kinase galacturonan-binding domain); GO:0004672 (protein kinase activity), GO:0004674 (protein serine/threonine kinase activity), GO:0005524 (ATP binding), GO:0006468 (protein phosphorylation), GO:0030247 (polysaccharide binding) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
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•
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•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
2397
|
| Description: |
ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrial-like [Glycine max]; IPR004487 (Clp protease, ATP-binding subunit ClpX), IPR027417 (P-loop containing nucleoside triphosphate hydrolase); GO:0000166 (nucleotide binding), GO:0005524 (ATP binding), GO:0006457 (protein folding), GO:0017111 (nucleoside-triphosphatase activity), GO:0051082 (unfolded protein binding) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
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•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
1002
|
| Description: |
sugar transport protein 13 [Glycine max]; IPR005828 (General substrate transporter), IPR016196 (Major facilitator superfamily domain, general substrate transporter); GO:0005215 (transporter activity), GO:0006810 (transport), GO:0016020 (membrane), GO:0016021 (integral component of membrane), GO:0022857 (transmembrane transporter activity), GO:0055085 (transmembrane transport) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
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•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
2193
|
| Description: |
receptor-like protein kinase 4; IPR011009 (Protein kinase-like domain), IPR013320 (Concanavalin A-like lectin/glucanase, subgroup), IPR025287 (Wall-associated receptor kinase galacturonan-binding domain); GO:0004672 (protein kinase activity), GO:0004674 (protein serine/threonine kinase activity), GO:0005524 (ATP binding), GO:0006468 (protein phosphorylation), GO:0030247 (polysaccharide binding) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
2322
|
| Description: |
Protein kinase family protein; IPR011009 (Protein kinase-like domain), IPR013320 (Concanavalin A-like lectin/glucanase, subgroup), IPR018392 (LysM domain); GO:0004672 (protein kinase activity), GO:0004674 (protein serine/threonine kinase activity), GO:0005524 (ATP binding), GO:0006468 (protein phosphorylation), GO:0016998 (cell wall macromolecule catabolic process) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
276
|
| Description: |
sugar transport protein 13 [Glycine max]; IPR005828 (General substrate transporter), IPR016196 (Major facilitator superfamily domain, general substrate transporter); GO:0005215 (transporter activity), GO:0006810 (transport), GO:0016020 (membrane), GO:0016021 (integral component of membrane), GO:0022857 (transmembrane transporter activity), GO:0055085 (transmembrane transport) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
1971
|
| Description: |
receptor-like protein kinase 1; IPR011009 (Protein kinase-like domain), IPR013320 (Concanavalin A-like lectin/glucanase, subgroup), IPR025287 (Wall-associated receptor kinase galacturonan-binding domain); GO:0004672 (protein kinase activity), GO:0004674 (protein serine/threonine kinase activity), GO:0005524 (ATP binding), GO:0006468 (protein phosphorylation), GO:0030247 (polysaccharide binding) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
2158
|
| Description: |
receptor-like protein kinase 4; IPR011009 (Protein kinase-like domain), IPR013320 (Concanavalin A-like lectin/glucanase, subgroup), IPR025287 (Wall-associated receptor kinase galacturonan-binding domain); GO:0004672 (protein kinase activity), GO:0004674 (protein serine/threonine kinase activity), GO:0005524 (ATP binding), GO:0006468 (protein phosphorylation), GO:0030247 (polysaccharide binding) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
3103
|
| Description: |
protein kinase family protein; IPR011009 (Protein kinase-like domain), IPR013320 (Concanavalin A-like lectin/glucanase, subgroup), IPR014729 (Rossmann-like alpha/beta/alpha sandwich fold); GO:0004672 (protein kinase activity), GO:0004674 (protein serine/threonine kinase activity), GO:0005524 (ATP binding), GO:0006468 (protein phosphorylation), GO:0006950 (response to stress) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
