Nucleolar GTP-binding protein 1 is involved in the biogenesis of the 60S ribosomal subunit [
]. It is found as part of the pre-60S complex in nucleolus [].
This group represents the GTP-binding protein EngA that belongs to the GTPase Der subfamily. In Escherichia coli, EngA is involved in ribosome stability and/or biogenesis, as well as cell viability [
]. In Salmonella typhimurium however, EngA binds with higher affinity to GDP than GTP [].
This family represents tRNA-specific 2-thiouridylase (sometimes called tRNA(5-methylaminomethyl-2-thiouridine)-methyltransferase), which is involved in the biosynthesis of the modified nucleoside 5-methylaminomethyl-2-thiouridine (mnm5s2U) present in the wobble position of some tRNAs [
]. This family of enzyme only presents in bacteria and eukaryote. The archaeal counterpart of this enzyme performs same function, but is completely unrelated in sequence [].
Quinohemoprotein amine dehydrogenase (QHNDH) from Paracoccus denitrificans is a heterotrimer consisting of alpha, beta and gamma chains [
]. The alpha chain has a four-domain structure that includes a dihaem cytochrome c, the beta chain forms a 7-bladed β-propeller that is part of the enzyme active site, and the gamma chain contains the redox factor cysteine tryptophylquinone (CTQ).The beta chain of QHNDH structurally resembles the 7-bladed beta propeller of the H chain of the periplasmic quinoprotein methylamine dehydrogenase (MADH), found in methylotrophic bacteria [
]. MADH is a heterotetramer consisting of two heavy (H) chains and two light (L) chains, and contains the redox cofactor tryptophan tryptophylquinone (TTQ). There is no similarity between the quinone-containing chains of MAD and QHNDH.The β-propeller structure found in MAD and QHNDH is similar to the YVTN (Tyr-Val-Thr-Asn) repeat that folds into a β-propeller found in the N-terminal domain of archaeal surface layer proteins, which help protect cells from extreme environments [
].
The proteins listed below share a common architecture with a protein kinase homology domain (see
) followed by an ~135-residue globular kinase-extension nuclease (KEN) domain made of eight helices [
]: Mammalian 2-5A-dependent RNase or RNase L (EC 3.1.26.-), an interferon-induced enzyme implicated in both the molecular mechanisms of interferon action and the fundamental control of RNA stability. 2-5A-dependent RNase is a unique enzyme in that it requires 2-5A, unusual oligoadenylates with 2',5'-phosphodiester linkages. RNase L is catalytically active only after binding to an unusual activator molecule containing a 5'-phosphorylated 2', 5'-linked oligoadenylate (2-5A), in the N-terminal half. RNase L consists of three domains, namely the N-terminal ankyrin repeat domain (see
), the protein kinase homology domain, and the C-terminal KEN domain [
,
,
].Eukaryotic Ire1/Ern1, an ancient transmembrane sensor of endoplasmic reticulum (ER) stress with dual protein kinase and ribonuclease activities. In response to ER stress Ire1/Ern1 catalyzes the splicing of target mRNAs in a spliceosome-independent manner. Ire1/Ern1 is a type 1 transmembrane receptor consisting of an N-terminal ER luminal domain, a transmembrane segment and a cytoplasmic region. The cytoplasmic region encompasses a protein kinase domain followed by a C-terminal KEN domain [
,
]. The dimerisation of the kinase domain activates the ribonuclease function of the KEN domain [
].
This entry represents the CTAG/Pcc1 family. Its members include yeast EKC/KEOPS complex subunit Pcc1, mammalian EKC/KEOPS complex subunit Lage3 and human cancer/testis antigen (CTAG) 1/2. In Saccharomyces cerevisiae, Pcc1 is a component of the EKC/KEOPS protein complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t6A37) in tRNAs that read codons beginning with adenine [
].Similar to its S. cerevisiae homologue, human Lage3 is part of the EKC complex that is essential for a universal tRNA modification. The human EKC complex interacts with tumour antigen PRAME (preferentially expressed antigen in melanoma), and hence involved in oncogenesis [
]. Human CTAG 1 and 2 (also known as NY-ESO-1 and 2) share protein sequence similarity with Pcc1, however, their function is not clear. They are linked to cancer progression [
].
This domain superfamily is found inserted into bacterial SAM-dependent methyltransferases and is thought to be involved in methyl acceptor selectivity. In contrast with recognition domains found in other methyltransferases, it is inserted into the centre of the protein sequence and has an alpha orthogonal structure rather than a simple loop or single α-helix [
].
RsmH (previously known as MraW) is a methyltransferase responsible for one of the two methylations (N4-methylation) of C1402 in Escherichia coli 16S rRNA. The N4, 2'-O-dimethylcytidine (m4Cm) at position 1402 of the 16S rRNA directly interacts with the P-site codon of the mRNA. These conserved methyl-modifications may play a role in fine-tuning the shape and function of the P-site, thus increasing decoding fidelity [
].
This domain is found in MutL and homologues and is characterized by a ribosomal protein S5 domain 2-like fold [
].The dimeric MutL protein has a key function in communicating mismatch recognition by MutS to downstream repair processes. Mismatch repair contributes to the overall fidelity of DNA replication by targeting mispaired bases that arise through replication errors during homologous recombination and as a result of DNA damage. It involves the correction of mismatched base pairs that have been missed by the proofreading element of the DNA polymerase complex [
].
This entry represents the N-terminal domain of DNA mismatch repair proteins, such as MutL. Bacterial MutL proteins are homodimers, while their eukaryotic homologues form heterodimers consisting of the MutL homologue Mlh1 and either Pms1, Pms2 or Mlh3 [
,
]. MutL proteins and their homologues share sequence homology at their N termini over the first 300-400 residues; the C termini are less well conserved, they constitute the main dimerization domain and are required for interaction between MutL and UvrD helicase []. The activity of the protein is modulated by the ATP-dependent dimerization of the N-terminal domain [].The dimeric MutL protein has a key function in communicating mismatch recognition by MutS to downstream repair processes. Mismatch repair contributes to the overall fidelity of DNA replication by targeting mispaired bases that arise through replication errors during homologous recombination and as a result of DNA damage. It involves the correction of mismatched base pairs that have been missed by the proofreading element of the DNA polymerase complex [
].
MutL and MutS are key components of the DNA repair machinery that corrects replication errors [
]. MutS recognises mispaired or unpaired bases in a DNA duplex and in the presence of ATP, recruits MutL to form a DNA signalling complex for repair. The N-terminal region of MutL contains the ATPase domain and the C-terminal is involved in dimerisation [].
The EH (for Eps15 Homology) domain is a protein-protein interaction module of approximately 95 residues which was originally identified as a repeated sequence present in three copies at the N terminus of the tyrosine kinase substrates Eps15 and Eps15R [
,
]. The EH domain was subsequently found in several proteins implicated in endocytosis, vesicle transport and signal transduction in organisms ranging from yeast to mammals. EH domains are present in one to three copies and they may include calcium-binding domains of the EF-hand type [,
]. Eps15 is divided into three domains: domain I contains signatures of a regulatory domain, including a candidate tyrosine phosphorylation site and EF-hand-type calcium-binding domains, domain II presents the characteristic heptad repeats of coiled-coil rod-like proteins, and domain III displays a repeated aspartic acid-proline-phenylalanine motif similar to a consensus sequence of several methylases [].EH domains have been shown to bind specifically but with moderate affinity to peptides containing short, unmodified motifs through predominantly hydrophobic interactions. The target motifs are divided into three classes: class I consists of the concensus Asn-Pro-Phe (NPF) sequence; class II consists of aromatic and hydrophobic di- and tripeptide motifs, including the Phe-Trp (FW), Trp-Trp (WW), and Ser-Trp-Gly (SWG) motifs; and class III contains the His-(Thr/Ser)-Phe motif (HTF/HSF) [
,
]. The structure of several EH domains has been solved by NMR spectroscopy. The fold consists of two helix-loop-helix characteristic of EF-hand domains, connected by a short antiparallel β-sheet. The target peptide is bound in a hydrophobic pocket between two alpha helices. Sequence analysis and structural data indicate that not all the EF-hands are capable of binding calcium because of substitutions of the calcium-liganding residues in the loop [,
,
]. This domain is often implicated in the regulation of protein transport/sorting and membrane trafficking. Messenger RNA translation initiation and cytoplasmic poly(A) tail shortening require the poly(A)-binding protein (PAB) in yeast. The PAB-dependent poly(A) ribonuclease (PAN) is organised into distinct domains containing repeated sequence elements [
].
The cation diffusion facilitator family (CDF) have members in both prokaryotes and eukaryotes, several of which have been shown to transport cobalt, cadmium and/or zinc. CDF transporters share a common two-modular architecture, consisting of a transmembrane domain (TMD) followed by a C-terminal domain (CTD) protruding into the cytoplasm [
].This superfamily represents the CDF N-terminal transmembrane domain.
Members of this family are integral membrane proteins, that
are found to increase tolerance to divalent metal ions suchas cadmium, zinc, and cobalt. These proteins are considered to
be efflux pumps that remove these ions from cells [,
], however others are implicated in ion uptake []. Thefamily has six predicted transmembrane domains. Members of the family are variable
in length because of variably sized inserts, often containing low-complexity sequence.
This entry represents the G protein gamma subunit and the GGL (G protein gamma-like) domain, which are related in sequence and are comprised of an extended α-helical polypeptide. The G protein gamma subunit forms a stable dimer with the beta subunit, but it does not make any contact with the alpha subunit, which contacts the opposite face of the beta subunit. The GGL domain is found in several RGS (regulators of G protein signaling) proteins. GGL domains can interact with beta subunits to form novel dimers that prevent gamma subunit binding, and may prevent heterotrimer formation by inhibiting alpha subunit binding. The interaction between G protein beta-5 neuro-specific isoforms and RGS GGL domains may represent a general mode of binding between β-propeller proteins and their partners [
].
This domain, found mainly in the eukaryotic lunapark proteins, has no known function [
]. C. elegans lunapark-1 plays a role in synaptogenesis by regulating vesicular transport or localization [].
Rab proteins constitute a family of small GTPases that serve a regulatory
role in vesicular membrane traffic [,
]; C-terminal geranylgeranylation iscrucial for their membrane association and function. This post-translational
modification is catalysed by Rab geranylgeranyl transferase (Rab-GGTase), a multi-subunit enzyme that contains a catalytic heterodimer and an accessory
component, termed Rab escort protein (REP)-1 []. REP-1 presents newly-synthesised Rab proteins to the catalytic component, and forms a stable
complex with the prenylated proteins following the transfer reaction. The mechanism of REP-1-mediated membrane association of Rab5 is similar
to that mediated by Rab GDP dissociation inhibitor (GDI). REP-1 and Rab GDI also share other functional properties, including the ability to inhibit the
release of GDP and to remove Rab proteins from membranes.The crystal structure of the bovine alpha-isoform of Rab GDI has been
determined to a resolution of 1.81A []. The protein is composed of twomain structural units: a large complex multi-sheet domain I, and a smaller
α-helical domain II.The structural organisation of domain I is closely related to FAD-containing
monooxygenases and oxidases []. Conserved regions common to GDI and thechoroideraemia gene product, which delivers Rab to catalytic subunits of
Rab geranylgeranyltransferase II, are clustered on one face of the domain[
]. The two most conserved regions form a compact structure at the apex ofthe molecule; site-directed mutagenesis has shown these regions to play a
critical role in the binding of Rab proteins [].
Methyltransferases (Mtases) are responsible for the transfer of methyl groups between two molecules. The transfer of the methyl group from the ubiquitous S-adenosyl-L-methionine (AdoMet) to nitrogen, oxygen or carbon atoms is frequently employed in diverse organisms. The reactions are catalysed by Mtases and modify DNA, RNA, proteins or small molecules, such as catechol, for regulatory purposes. Members of this family are predicted to be Mtases based on the crystal structure (1TO0) and its close structural homology to other structures (1VHK,1MXI,1IPA,1K3R) that have methyltransferase activity [
].
This entry represents a family of nucleoside-triphosphatases which have activity towards ATP, GTP, CTP, TTP and UTP and may hydrolyse nucleoside diphosphates with lower efficiency [
]. It includes proteins from bacteria to human, and the function was determined first in a hyperthermophilic bacterium to be an NTPase []. The structure of one member-sequence represents a variation of the RecA fold, and implies that the function might be that of a DNA/RNA modifying enzyme []. The sequence carries both a Walker A and Walker B motif which together are characteristic of ATPases or GTPases. The protein exhibits an increased expression profile in human liver cholangiocarcinoma when compared to normal tissue [].
This entry represents the mitochondrial pyruvate carrier proteins, including Mpc 1/2 and their homologues. They mediate the uptake of pyruvate into mitochondria [
]. In humans, Mpc1 and Mpc2 associate to form an ~150-kilodalton complex in the inner mitochondrial membrane [].
Members of this family have been called SAND proteins [
] although these proteins do not contain a SAND domain. In Saccharomyces cerevisiae, Mon1 is part of the Mon1-Ccz1 complex that acts as the guanine nucleotide exchange factor (GEF) of the yeast Rab7 GTPase Ypt7 [,
]. The Mon1/Ccz1 complex is conserved in eukaryotic evolution and members of this family (previously known as DUF254) are distant homologues to domains of known structure that assemble into cargo vesicle adapter (AP) complexes [,
].
Phosphatidylinositol-glycan biosynthesis class S protein
Type:
Family
Description:
Phosphatidylinositol-glycan biosynthesis class S protein (PIG-S, also known as Gpi17 in budding yeasts) is one of several key, core components of the glycosylphosphatidylinositol (GPI) trans-amidase complex that adds GPIs to newly synthesized proteins [
]. Mammalian GPI transamidase consists of at least five components: Gaa1, Gpi8, PIG-S, PIG-T, and PIG-U, all five of which are required for its function. It is possible that Gaa1, Gpi8, PIG-S, and PIG-T form a tightly associated core that is only weakly associated with PIG-U [].
This family represents eukaryotic protein disulphide isomerases retained in the endoplasmic reticulum (ER) and other closely related forms [
]. Some members have been assigned alternative or additional functions such as prolyl 4-hydroxylase [,
]. Members of this family have at least two protein-disulphide domains, each similar to thioredoxin but with the redox-active disulphide in the motif PWCGHCK, and an ER retention signal at the extreme C terminus (KDEL, HDEL, and similar motifs).
This entry includes budding yeast Sit4-associated proteins, such as Sap155, Sap185, and Sap190. Sit4 is a phosphatase involved in a variety of processes including transcription, translation, bud formation, glycogen metabolism, monovalent ion homeostasis, H+ transport, and telomere function [
]. This entry also includes mammalian PP6 (Sit4 homologue)-associated proteins, such as PP6R1, PP6R2, and PP6R3 [
]. They are regulatory subunits of PP6 involved in the PP6-mediated dephosphorylation of NFKBIE opposing its degradation in response to TNF-alpha [].
This family consists of several heparan sulphate 6-sulphotransferase (HS6ST) proteins. Heparan sulphate 6-O-sulphotransferase (HS6ST) catalyses the transfer of sulphate from adenosine 3'-phosphate, 5'-phosphosulphate to the 6th position of the N-sulphoglucosamine residue in heparan sulphate [
]. This entry also includes protein-tyrosine sulfotransferase, which catalyses the O-sulfation of tyrosine residues within acidic motifs of polypeptides [].
The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases. These enzymes catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. A classification of glycosyltransferases using nucleotide diphospho-sugar, nucleotide monophospho-sugar and sugar phosphates ([intenz:2.4.1.-]) and related proteins into distinct sequence based families has been described []. This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. The same three-dimensional fold is expected to occur within each of the families. Because 3-D structures are better conserved than sequences, several of the families defined on the basis of sequence similarities may have similar 3-D structures and therefore form 'clans'.This domain is found in a diverse family of glycosyl transferases that transfer the sugar from UDP-glucose, UDP-N-acetyl-galactosamine, GDP-mannose or CDP-abequose, to a range of substrates including cellulose, dolichol phosphate and teichoic acids [
].
Leucine-rich repeats (LRR) consist of 2-45 motifs of 20-30 amino acids in length that generally folds into an arc or horseshoe shape [
]. LRRs occur in proteins ranging from viruses to eukaryotes, and appear to provide a structural framework for the formation of protein-protein interactions [,
].Proteins containing LRRs include tyrosine kinase receptors, cell-adhesion molecules, virulence factors, and extracellular matrix-binding glycoproteins, and are involved in a variety of biological processes, including signal transduction, cell adhesion, DNA repair, recombination, transcription, RNA processing, disease resistance, apoptosis, and the immune response [,
].Sequence analyses of LRR proteins suggested the existence of several different subfamilies of LRRs. The significance of this classification is that repeats from different subfamilies never occur simultaneously and have most probably evolved independently. It is, however, now clear that all major classes of LRR have curved horseshoe structures with a parallel beta sheet on the concave side and mostly helical elements on the convex side. At least six families of LRR proteins, characterised by different lengths and consensus sequences of the repeats, have been identified. Eleven-residue segments of the LRRs (LxxLxLxxN/CxL), corresponding to the β-strand and adjacent loop regions, are conserved in LRR proteins, whereas the remaining parts of the repeats (herein termed variable) may be very different. Despite the differences, each of the variable parts contains two half-turns at both ends and a "linear"segment (as the chain follows a linear path overall), usually formed by a helix, in the middle. The concave face and the adjacent loops are the most common protein interaction surfaces on LRR proteins.
3D structure of some LRR proteins-ligand complexes show that the concave surface of LRR domain is ideal for interaction with α-helix, thus supporting earlier conclusions that the elongated and curved LRR structure provides an outstanding framework for achieving diverse protein-protein interactions []. Molecular modeling suggests that the conserved pattern LxxLxL, which is shorter than the previously proposed LxxLxLxxN/CxL is sufficient to impart the characteristic horseshoe curvature to proteins with 20- to 30-residue repeats []. This entry includes some LRRs that fail to be detected by
[
,
].
This entry includes a group of meiosis specific proteins, including Spo22 from budding yeasts, ZIP4 from plants and TEX11 from mammals. They play an important role in normal crossover formation and meiotic chromosome segregation [
,
,
]. Impairment of these functions results in meiosis I (MI) segregation defect [].
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 [].Glycyl-tRNA synthetase exhibits different oligomeric structures in different organisms (alpha2 beta2 and alpha2) [
]. This entry represents the alpha and beta subunits of heterodimeric glycine-tRNA synthetases.
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.
This entry represents the alpha subunit of glycine-tRNA ligase (also known as glycyl-tRNA synthetase alpha subunit). It is responsible for the attachment of glycine to the 3' OH group of ribose of the appropriate tRNA. This domain is primarily responsible for the ATP-dependent formation of the enzyme bound aminoacyl-adenylate.In eubacteria, glycine-tRNA ligase (
) is an alpha2/beta2 tetramer composed of 2 different subunits [
,
,
]. In some eubacteria, in archaea and eukaryota, glycine-tRNA ligase is an alpha2 dimer (see ). It belongs to class IIc and is one of the most complex ligases. What is most interesting is the lack of similarity between the two types: divergence at the sequence level is so great that it is impossible to infer descent from common genes. The alpha 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 (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 RWD domain is a conserved region of about 110 amino acid residues, which
has been identified in the mouse GCN2 eIF2alpha kinase and histidyl-tRNAsynthetase and in presumed orthologues in other eukaryotic species from yeast to
vertebrates. Additionally, it is also found in WD repeat containing proteins,yeast DEAD (DEXD)-like helicases, many RING-finger containing proteins, the
UPF0029 uncharacterised protein family and a range of hypothetical proteins. The RWD domain has been named after the better characterised RING finger and WD repeat containing proteins and DEAD-like helicases. It has been proposed that the RWD domain might have a function in protein interaction []. The RWD domain is predicted to have an alpha/beta secondary structure and is
thought to be related to ubiquitin-conjugating enzymes (UBCc) domain, althoughthe catalytic cysteine critical for ubiquitin-conjugating activity is not
conserved in most members of the novel subfamily [].
The signal recognition particle (SRP) is a multimeric protein, which along with its conjugate receptor (SR), is involved in targeting secretory proteins to the rough endoplasmic reticulum (RER) membrane in eukaryotes, or to the plasma membrane in prokaryotes [
,
]. SRP recognises the signal sequence of the nascent polypeptide on the ribosome. In eukaryotes this retards its elongation until SRP docks the ribosome-polypeptide complex to the RER membrane via the SR receptor []. Eukaryotic SRP consists of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72) and a single 300 nucleotide 7S RNA molecule. The RNA component catalyses the interaction of SRP with its SR receptor []. In higher eukaryotes, the SRP complex consists of the Alu domain and the S domain linked by the SRP RNA. The Alu domain consists of a heterodimer of SRP9 and SRP14 bound to the 5' and 3' terminal sequences of SRP RNA. This domain is necessary for retarding the elongation of the nascent polypeptide chain, which gives SRP time to dock the ribosome-polypeptide complex to the RER membrane. In archaea, the SRP complex contains 7S RNA like its eukaryotic counterpart, yet only includes two of the six protein subunits found in the eukarytic complex: SRP19 and SRP54 [].This entry represents the 9kDa SRP9 component. Both SRP9 and SRP14 have the same (beta)-α-β(3)-alpha fold. The heterodimer has pseudo two-fold symmetry and is saddle-like, consisting of a curved six-stranded β-sheet that has four helices packed on the convex side and an exposed concave surface lined with positively charged residues. The SRP9/SRP14 heterodimer is essential for SRP RNA binding, mediating the pausing of synthesis of ribosome associated nascent polypeptides that have been engaged by the targeting domain of SRP [
].
The VHS domain is an about 150 residues long domain, whose name is derived
from its occurrence in VPS-27, Hrs and STAM. The VHS domain is found at the N-termini of proteins associated with endocytocis and/or vesicular trafficking,
often in association with other domains like FYVE, SH3 or TAM [,
]. The VHS domain of Hrs makes both intra- andintermolecular interactions with FYVE domains and it has been proposed that it
might as well interact with other domains. The VHS domain might function as amultipurpose docking adapter that localizes proteins to the membrane through
interactions with the membrane and/or the endocytic machinery [,
].Resolution of the crystal structure of the VHS domain of Drosophila Hrs and
human Tom1 revealed that it consists of eight helices arranged in a superhelix[
,
].
The GAT domain is a region of homology of ~130 residues, which is found in eukaryotic GGAs (for Golgi-localized, gamma ear-containing ADP ribosylation factor (ARF)-binding proteins) and vertebrate TOMs (for target of myb). The GAT domain is found in its entirety only in GGAs, although, at the C terminus it shares partial sequence similarity with a short region of TOMs. The GAT domain is found in association with other domains, such as VHS and GAE. The GAT domain of GGAs serves as a molecular anchor of GGA to trans-Golgi network (TGN) membranes via its interaction with the GTP-bound form of a member of the ARF family of small GTPases and can bind specifically to the Rab GTPase effector rabaptin5 and to ubiquitin [
,
,
,
].The GGA-GAT domain possesses an all α-helical structure, composed of four helices arranged in a somewhat unusual topology, which has been called the helical paper clip. The overall structure shows that the GAT domain has an elongated shape, in which the longest helix participates in two small independent subdomains: an N-terminal helix-loop-helix hook and a C-terminal three-helix bundle. The hook subdomain has been shown to be both necessary and sufficient for ARF-GTP binding and Golgi targeting of GGAs. The N-terminal hook subdomain contains a hydrophobic patch, which is found to interact directly with ARF [
]. It has been proposed that this interaction might stabilise the hook subdomain []. The C-terminal three-helix bundle is involved in the binding with Rabaptin5 and ubiquitin [].
Metallothioneins (MT) are small proteins that bind heavy metals, such as zinc, copper, cadmium, nickel, etc. They have a high content of cysteine residues that bind the metal ions through clusters of thiolate bonds [
,
,
,
]. An empirical classification into three classes has been proposed by Fowler and coworkers [] and Kojima []. Members of class I are defined to include polypeptides related in the positions of their cysteines to equine MT-1B, and include mammalian MTs as well as MTs from crustaceans and molluscs. Class II groups MTs from a variety of species, including sea urchins, fungi, insects and cyanobacteria. Class III MTs are atypical polypeptides composed of gamma-glutamylcysteinyl units []. This original classification system has been found to be limited, in the sense that it does not allow clear differentiation of patterns of structural similarities, either between or within classes. Consequently, all class I and class II MTs (the proteinaceous sequences) have now been grouped into families of phylogenetically-related and thus alignable sequences. This system subdivides the MT superfamily into families, subfamilies, subgroups, and isolated isoforms and alleles.
The metallothionein superfamily comprises all polypeptides that resemble equine renal metallothionein in several respects []: e.g., low molecular weight; high metal content; amino acid composition with high Cys and low aromatic residue content; unique sequence with characteristic distribution of cysteines, and spectroscopic manifestations indicative of metal thiolate clusters. A MT family subsumes MTs that share particular sequence-specific features and are thought to be evolutionarily related. The inclusion of a MT within a family presupposes that its amino acid sequence is alignable with that of all members. Fifteen MT families have been characterised, each family being identified by its number and its taxonomic range: e.g., Family 1: vertebrate MTs.Family 15 consists of planta MTs. Its members are recognised by the sequence pattern [YFH]-x(5,25)-C-[SKD]-C-[GA]-[SDPAT]-x(0,1)-C-x-[CYF] which yields all plant sequences, but also MTCU_HELPO and the non-MT ITB3_HUMAN. The taxonomic range of the members extends to planta. Planta MTs are 45-84 residue proteins, containing 17 conserved cysteines that bind 5 zinc ions. Generally, there are two Cys-rich regions (domain 1 and domain 3) separated by a Cys-poor region (domain 2) and only the domain 2 contains unusual residues. It is believed that the proteins may have a role in Zn2+homeostasis during embryogenesis. Family 15 includes the following subfamilies: p1, p2, p2v, p3, pec, p21.
Protein prenylation is the posttranslational attachment of either a farnesyl group or a geranylgeranyl group via a thioether linkage (-C-S-C-) to a cysteine at or near the carboxyl terminus of the protein. Farnesyl and geranylgeranyl groups are polyisoprenes, unsaturated hydrocarbons with a multiple of five carbons; the chain is 15 carbons long in the farnesyl moiety and 20 carbons long in the geranylgeranyl moiety. There are three different protein prenyltransferases in humans: farnesyltransferase (FT) and geranylgeranyltransferase 1 (GGT1) share the same motif (the CaaX box) around the cysteine in their substrates, and are thus called CaaX prenyltransferases, whereas geranylgeranyltransferase 2 (GGT2, also called Rab geranylgeranyltransferase) recognises a different motif and is thus called a non-CaaX prenyltransferase. Protein prenyltransferases are currently known only in eukaryotes, but they are widespread, being found in vertebrates, insects, nematodes, plants, fungi and protozoa, including several parasites. Each protein consists of two subunits, alpha and beta; the alpha subunit of FT and GGT1 is encoded by the same gene, FNTA. The alpha subunit is thought to participate in a stable complex with the isoprenyl substrate; the beta subunit binds the peptide substrate. In the alpha subunits of both types of protein prenyltransferases, seven tetratricopeptide repeats are formed by pairs of helices that are stabilised by conserved intercalating residues. The alpha subunits of GGT2 in mammals and plants also have an immunoglobulin-like domain between the fifth and sixth tetratricopeptide repeat, as well as leucine-rich repeats at the carboxyl terminus. The functions of these additional domains in GGT2 are as yet undefined, but they are apparently not directly involved in the interaction with substrates and Rab escort proteins. The tetratricopeptide repeats of the alpha subunit form a right-handed superhelix, which embraces the (α-α)6 barrel of the beta subunit [
].
O-Glycosyl hydrolases (
) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families [
,
]. This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.Glycoside hydrolase family 35
comprises enzymes with only one known activity; beta-galactosidase (
).
Mammalian beta-galactosidase is a lysosomal enzyme (gene GLB1) which cleaves the terminal galactose from gangliosides, glycoproteins, and glycosaminoglycans and whose deficiency is the cause of the genetic disease Gm(1) gangliosidosis (Morquio disease type B).One of the best conserved regions in these enzymes contains a glutamic acid residue which, on the basis of similarities with other families of glycosyl hydrolases, probably acts as the proton donor in the catalytic mechanism. This signature spans the region contain the putative active site glutamic acid residue, it is the second glutamic acid residue of the two in the pattern [
].
D-galactoside/L-rhamnose binding SUEL lectin domain
Type:
Domain
Description:
The D-galactoside binding lectin purified from sea urchin (Anthocidaris crassispina) eggs exists as a disulphide-linked homodimer of two subunits; the dimeric form is essential for hemagglutination activity [
]. The sea urchin egg lectin (SUEL) forms a new class of lectins. Although SUEL was first isolated as a D-galactoside binding lectin, it was latter shown that it bind to L-rhamnose preferentially [,
]. L-rhamnose and D-galactose share the same hydroxyl group orientation at C2 and C4 of the pyranose ring structure.A cysteine-rich domain homologous to the SUEL protein has been identified in the following proteins [
,
,
]:Plant beta-galactosidases (
) (lactases).
Mammalian latrophilin, the calcium independent receptor of alpha-latrotoxin (CIRL). The galactose-binding lectin domain is not required for alpha-latratoxin binding [
].Human lectomedin-1.Rhamnose-binding lectin (SAL) from catfish (Silurus asotus, Namazu) eggs. This protein is composed of three tandem repeat domains homologous to the SUEL lectin domain. All cysteine positions of each domain are completely conserved [
].The hypothetical B0457.1, F32A7.3A and F32A7.3B proteins from Caenorhabditis elegans.The human KIAA0821 protein.
The cells at the periphery of the root cap are continuously sloughed off from the root into the mucilage, and are thought to be programmed to die [
].This family represents a conserved region approximately 60 residues in length within plant root cap proteins, which may be involved in the process.
CDC45 is an essential gene required for initiation of DNA replication in Saccharomyces cerevisiae (cell division control protein 45), forming a complex with MCM5/CDC46. Homologs of CDC45 have been identified in human [
], mouse and the smut fungus, Melampsora spp., (tsd2 protein) among others.
This domain has been shown to bind preferentially to dsRNA [
]. This domain is found in Sua5 () and carbamoyltransferase HypF. The Sua5 family is required for the formation of threonylcarbamoyladenosine in tRNA [
]. Sua5 has been shown to be required for translational regulation [] and telomere recombination in yeast [].
This family consists of (uracil-5-)-methyltransferases
from bacteria, archaea and eukaryotes. They are class I-like SAM-binding methyltransferases.
Methyltransferases (MTs) (EC 2.1.1.-) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as nitrogen, oxygen, sulfur or carbon leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule. The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids. MTs are therefore involved in many essential cellular processes including biosynthesis, signal
transduction, protein repair, chromatin regulation and gene silencing [,
,
].More than 230 different enzymatic reactions of MTs have been described so far, of which more than 220 use SAM as the methyl donor. A review published in 2003 [
] divides all MTs into 5 classes based on the structure of their catalytic domain (fold):class I: Rossmann-like α/βclass II: TIM beta/α-barrel α/βclass III: tetrapyrrole methylase α/βclass IV: SPOUT α/β class V: SET domain all β A more recent paper [
] based on a study of the Saccharomyces cerevisiae methyltransferome argues for four more folds:class VI: transmembrane all αclass VII: DNA/RNA-binding 3-helical bundle all αclass VIII: SSo0622-like α+βclass IX: thymidylate synthetase α+βThe vast majority of MTs belong to the Rossmann-like fold (Class I) which
consists in a seven-stranded β-sheet adjoined by α-helices. The β-sheet contains a central topological switch-point resulting in a deep cleft inwhich SAM binds. Class I MTs display two conserved positions, the first one is
a GxGxG motif (or at least a GxG motif) at the end of the first β-strandwhich is characteristic of a nucleotide-binding site and is hence used to bind
the adenosyl part of SAM, the second conserved position is an acidic residueat the end of the second β-strand that forms one hydrogen bond to each
hydroxyl of the SAM ribose part. The core of these enzymes is composed byabout 150 amino acids that show very strong spatial conservation. Catechol O-
MT (EC 2.1.1.6) is the canonical Class I MT considering that it consists inthe exact consensus structural core with no extra domain [
].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].This entry represents the S27a ribosomal domain from both archaea and eukaryotes. In eukaryotes, the 40S ribosomal protein S27a is synthesized as a C-terminal extension of ubiquitin (
), and this fusion protein is known as UBS27 [
]. The S27a domain compromises the C-terminal half of the protein. The synthesis of ribosomal proteins as extensions of ubiquitin promotes their incorporation into nascent ribosomes by a transient metabolic stabilisation and is required for efficient ribosome biogenesis []. The ribosomal extension protein S27a contains a basic region that is proposed to form a zinc finger; its fusion gene is proposed as a mechanism to maintain a fixed ratio between ubiquitin necessary for degrading proteins and ribosomes a source of proteins [].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [,
].Ribosomal protein L13 is one of the proteins from the large ribosomal subunit
[]. In Escherichia coli, L13 is known to be one of the early assembly proteins of the 50S ribosomal subunit. This model represents ribosomal protein of L13 from the Archaea and from the eukaryotic cytosol.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].Ribosomal protein L13 is one of the proteins from the large ribosomal subunit [
]. In Escherichia coli, L13 is known to be one of the early assembly proteins of the 50S ribosomal subunit.The signature pattern of this entry is a conserved region located in the C-terminal section of these proteins.
Ribosomal protein L13 is one of the proteins from the large ribosomal subunit [
]. In Escherichia coli, L13 is known to be one of the early assembly proteins of the 50S ribosomal subunit.Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [,
].
Group II introns are widespread in plant cell organelles [
]. In vivo, most plant group II introns do not self-splice, but require the assistance of proteinaceous splicing factors, known as maturases. In higher plants, maturases are encoded for in the nuclear genes [], but are otherwise encoded by organellar introns. This entry represents a sequence region known as domain X, which is conserved in group II introns [
] and is required for maturase function [].
ATPase family AAA domain-containing protein 3, N-terminal
Type:
Domain
Description:
This is the conserved N-terminal domain of ATPase family AAA domain-containing protein 3 (ATAD3) which is involved in dimerisation [
] and interacts with the inner surface of the outer mitochondrial membrane []. This domain is found associated with the AAA ATPase domain . ATAD3 is essential for mitochondrial network organisation, mitochondrial metabolism and cell growth at organism and cellular level. It may also play an important role in mitochondrial protein synthesis.
Thaumatin [
] is an intensely sweet-tasting protein, 100 000 times sweeter than sucrose on a molar basis [], found in berries from Thaumatococcus daniellii, a tropical flowering plant known as Katemfe. It is induced by attack by viroids, which are single-stranded unencapsulated RNA molecules that do not code for protein.Thaumatin consists of about 200 residues and contains 8 disulphide bonds. Like other PR proteins, thaumatin is predicted to have a mainly beta structure, with a high content of β-turns and little helix []. Several stress-induced proteins of plants have been found to be related to thaumatins:A maize alpha-amylase/trypsin inhibitorTwo tobacco pathogenesis-related proteins: PR-R major and minor forms, which are induced after infection with virusesSalt-induced protein NP24 from tomatoOsmotin, a salt-induced protein from tobacco [
]
Osmotin-like proteins OSML13, OSML15 and OSML81 from potato [
]
P21, a leaf protein from soybeanPWIR2, a leaf protein from wheat [
]
Zeamatin, a maize antifungal protein [
]
This family is also referred to as pathogenesis-related group 5 (PR5), as many thaumatin-like proteins accumulate in plants in response to infection by a pathogen and possess antifungal activity [
]. The proteins are involved in systemically acquired resistance and stress response in plants, although their precise role is unknown []. The PR5K receptor protein kinase from Arabidopsis comprises an extracellular domain related to the PR5 proteins, and an intracellular protein-serine/threonine kinase domain [].
Ferredoxin reductase is a member of the flavoprotein pyridine nucleotide cytochrome reductases [
] (FPNCRs) that catalyse the interchange of reducing equivalents between one-electron carriers and the two-electron-carrying nicotinamide dinucleotides. Ferredoxin reductase catalyzes the final step of electron transfer to make NADPH and ATP in plant chloroplasts during photosynthesis. Other family members include plant and fungal:NAD(P)H:nitrate reductases [
,
]
NADH:cytochrome b5 reductases [
]
NADPH:P450 reductases [
]
NADPH:sulphite reductases [
]
nitric oxide synthases [
]
phthalate dioxygenase reductase [
]
various other flavoproteinsDespite functional similarities, FPNCRs show no sequence similarity to NADPH:adrenodoxin reductases [
], nor to bacterial ferredoxin:NAD reductases and their homologues []. To date, structures for a number of family members have been solved: Spinacia oleracea (Spinach) ferredoxin:NADP reductase [
]
Burkholderia cepacia (Pseudomonas cepacia) phthalate dioxygenase reductase [
]
Zea mays (Maize) nitrate reductase flavoprotein domain [
]
Sus scrofa (Pig) NADH:cytochrome b5 reductase [
]. In all of them, the FAD-binding domain (N-terminal) has the topology of an anti-parallel β-barrel, while the NAD(P)-binding domain (C-terminal) has the topology of a classical pyridine dinucleotide-binding fold (i.e. a central parallel β-sheet with 2 helices on each side) [].Proteins in this family also include benzoyl-CoA oxygenase component A (BoxA), which forms a complex with BoxB that catalyses the aerobic reduction/oxygenation of the aromatic ring of benzoyl-CoA to form 2,3-dihydro-2,3-dihydroxybenzoyl-CoA. BoxA also acts as a reductase that uses NADPH to reduce the oxygenase component BoxB. BoxAB does not act on NADH or benzoate [
].
Pyridoxal phosphate is the active form of vitamin B6 (pyridoxine or pyridoxal). Pyridoxal 5'-phosphate (PLP) is a versatile catalyst, acting as a coenzyme in a multitude of reactions, including decarboxylation, deamination and transamination [
,
,
]. PLP-dependent enzymes are primarily involved in the biosynthesis of amino acids and amino acid-derived metabolites, but they are also found in the biosynthetic pathways of amino sugars and in the synthesis or catabolism of neurotransmitters; pyridoxal phosphate can also inhibit DNA polymerases and several steroid receptors []. Inadequate levels of pyridoxal phosphate in the brain can cause neurological dysfunction, particularly epilepsy [].PLP enzymes exist in their resting state as a Schiff base, the aldehyde group of PLP forming a linkage with the ε-amino group of an active site lysine residue on the enzyme. The α-amino group of the substrate displaces the lysine ε-amino group, in the process forming a new aldimine with the substrate. This aldimine is the common central intermediate for all PLP-catalysed reactions, enzymatic and non-enzymatic [
].A number of pyridoxal-dependent decarboxylases share regions of sequence similarity, particularly in the vicinity of a conserved lysine residue, which provides the attachment site for the pyridoxal-phosphate (PLP) group [
,
]. Among these enzymes are aromatic-L-amino-acid decarboxylase (L-dopa decarboxylase or tryptophan decarboxylase), which catalyses the decarboxylation of tryptophan to tryptamine []; tyrosine decarboxylase, which converts tyrosine into tyramine; histidine decarboxylase, which catalyses the decarboxylation of histidine to histamine []; L-aspartate decarboxylase, which converts aspartate to beta-alanine []; and phenylacetaldehyde synthase that catalyses the decarboxylation of L-phenylalanine to 2-phenylethylamine []. These enzymes belong to the group II decarboxylases [,
].This signature contains the pyridoxal-phosphate-binding lysine residue. Certain pyridoxal-dependent decarboxylases seem to share regions of sequence similarity [
,
,
,
], especially in the vicinity of the lysine residue which serves as the attachment site for the pyridoxal-phosphate (PLP) group. These enzymes, known collectively as group II decarboxylases, are:Glutamate decarboxylase (
) (GAD), which catalyses the decarboxylation of glutamate into the neurotransmitter GABA (4-aminobutanoate).
Histidine decarboxylase (
) (HDC), which catalyses the decarboxylation of histidine to histamine. There are two completely unrelated types of HDC: those that use PLP as a cofactor (found in Gram-negative bacteria and mammals), and those that contain a covalently bound pyruvoyl residue (found in Gram-positive bacteria).
Aromatic-L-amino-acid decarboxylase (
) (DDC), also known as L-dopa decarboxylase or tryptophan decarboxylase, which catalyses the decarboxylation of tryptophan to tryptamine. It also acts on 5-hydroxy-tryptophan and dihydroxyphenylalanine (L-dopa).
Tyrosine decarboxylase (
) (TyrDC), which converts tyrosine into tyramine, a precursor of isoquinoline alkaloids and various amides.
Cysteine sulphinic acid decarboxylase (
).
L-2,4-diaminobutyrate decarboxylase (
) (DABA decarboxylase).
This entry also includes phenylacetaldehyde synthase and 4-hydroxyphenylacetaldehyde synthase from plants and 3,4-dihydroxyphenylacetaldehyde synthase from insects. Plant aromatic acetaldehyde syntheses (AASs) are effectively indistinguishable from plant aromatic amino acid decarboxylases (AAADs) through primary sequence comparison [
]. Proteins of the AAAD family are grouped together as a result of their high homology, pyridoxal-5'-phosphate (PLP) dependence, and aromatic substrate requirements []. Similarly 3,4-dihydroxylphenylacetaldehyde (DHPAA) from Aedes aegypti (Yellowfever mosquito) is classified into the aromatic amino acid decarboxylase (AAAD) family based on extremely high sequence homology (about 70%) with dopa decarboxylase (Ddc) but has been shown to catalyse the production of 3,4-dihydroxylphenylacetaldehyde (DHPAA) directly from L-dopa [].
A number of pyridoxal-dependent decarboxylases share regions of sequence similarity, particularly in the vicinity of a conserved lysine residue, which provides the attachment site for the pyridoxal-phosphate (PLP) group [
,
]. Among these enzymes are aromatic-L-amino-acid decarboxylase (L-dopa decarboxylase or tryptophan decarboxylase), which catalyses the decarboxylation of tryptophan to tryptamine []; tyrosine decarboxylase, whichconverts tyrosine into tyramine; and histidine decarboxylase, which catalyses the decarboxylation of histidine to histamine [
]. These enzymes belong to the group II decarboxylases [,
].
Histidinol dehydrogenase (HDH) catalyses the terminal step in the biosynthesis of histidine in bacteria, fungi, and plants, the four-electron oxidation of L-histidinol to histidine.In 4-electron dehydrogenases, a single active site catalyses 2 separate oxidation steps: oxidation of the substrate alcohol to an intermediate aldehyde; and oxidation of the aldehyde to the product acid, in this case His [
]. The reaction proceeds via a tightly- or covalently-bound inter-mediate, and requires the presence of 2 NAD molecules []. By contrast with most dehydrogenases, the substrate is bound before the NAD coenzyme []. A Cys residue has been implicated in the catalytic mechanism of the second oxidative step [].In bacteria HDH is a single chain polypeptide; in fungi it is the C-terminal domain of a multifunctional enzyme which catalyses three different steps of histidine biosynthesis; and in plants it is expressed as nuclear encoded protein precursor which is exported to the chloroplast [
].
Histidinol dehydrogenase (
) (HDH) catalyses the terminal step in the biosynthesis of histidine in bacteria, fungi, and plants, the four-electron oxidation of L-histidinol to histidine.
In 4-electron dehydrogenases, a single active site catalyses 2 separate oxidation steps: oxidation of the substrate alcohol to an intermediate aldehyde; and oxidation of the aldehyde to the product acid, in this case His [
]. The reaction proceeds via a tightly- or covalently-bound inter-mediate, and requires the presence of 2 NAD molecules []. By contrast with most dehydrogenases, the substrate is bound before the NAD coenzyme []. A Cys residue has been implicated in the catalytic mechanism of the second oxidative step [].In bacteria HDH is a single chain polypeptide; in fungi it is the C-terminal domain of a multifunctional enzyme which catalyzes three different steps of histidine biosynthesis; and in plants it is expressed as nuclear encoded protein precursor which is exported to the chloroplast [
].
3-hydroxyisobutyrate dehydrogenase is an enzyme that catalyzes the NAD+-dependent oxidation of 3-hydroxyisobutyrate to methylmalonate semialdehyde of the valine catabolism pathway. In Pseudomonas aeruginosa, 3-hydroxyisobutyrate dehydrogenase (mmsB) is co-induced with methylmalonate-semialdehyde dehydrogenase (mmsA) when grown on medium containing valine as the sole carbon source. The positive transcriptional regulator of this operon (mmsR) is located upstream of these genes and has been identified as a member of the XylS/AraC family of transcriptional regulators [
]. 3-hydroxyisobutyrate dehydrogenase shares high sequence homology to the characterised 3-hydroxyisobutyrate dehydrogenase from rat liver [
] with conservation of proposed NAD+ binding residues at the N terminus (G-8,10,13,24 and D-31). This enzyme belongs to the 3-hydroxyacid dehydrogenase family, sharing a common evolutionary origin and enzymatic mechanism with 6-phosphogluconate [
]. HIBADH exhibits sequence similarity to the NAD binding domain of 6-phosphogluconate dehydrogenase.
The yeast member of the Kri1-like family (Kri1p) is found to be required for 40S ribosome biogenesis in the nucleolus [
]. This entry represents the C-terminal domain of this protein family.
The budding yeast KRR1-interacting protein 1 (Kri1) is an essential nucleolar protein required for 40S ribosome biogenesis [
]. This entry also includes Kri1 homologues from animals and plants. Their function is not clear.
The TGS domain is present in a number of enzymes, for example, in threonyl-tRNA synthetase (ThrRS), GTPase, and guanosine 3',5'-bis(diphosphate) 3'-pyrophosphohydrolase (SpoT) [
]. The TGS domain is also present at the amino terminus of the uridine kinase from the spirochaete Treponema pallidum (but not any other organism, including the related spirochaete Borrelia burgdorferi). TGS is a small domain that consists of ~50 amino acid residues and is predicted to possess a predominantly β-sheet structure. There is no direct information on the functions of the TGS domain, but its presence in two types of regulatory proteins (the GTPases and guanosine polyphosphate phosphohydrolases/synthetases) suggests a ligand (most likely nucleotide)-binding, regulatory role [
]. The TGS domain is possibly related to the ubiquitin-like and MoaD/ThiS superfamilies, and has some similarity to the alpha-L RNA-binding motif.This superfamily represents TGS domain-containing proteins, as well as The C-terminal domain of bacterial and fungal YchF, a universally conserved GTPase whose function is unknown [
].
E. coli ribosome-binding ATPase YchF is an ATPase that binds to both the 70S ribosome and the 50S ribosomal subunit in a nucleotide-independent manner [
]. The mammalian homologue of YchF has been termed OLA1, for Obg-like ATPase 1 []. These proteins bind and hydrolyse ATP more efficiently than GTP, therefore their name. ATPase activity is a general feature of the YchF subfamily of Obg-like GTPases [].
This domain is found at the C terminus of YchF. The crystal structure of YchF
from Haemophilus influenzae has been determined [
]. This protein consists of three domains: an N-terminal domain which has a mononucleotide binding fold typical for the P-loop NTPases, a central domain which forms an α-helical coiled coil, and this C-terminal domain which is composed of a six-stranded half-barrel curved around an α-helix. The central domain and this domain are topologically similar to RNA-binding proteins, while the N-terminal region containsthe features typical of GTP-dependent molecular switches. The purified protein was capable of binding both double-stranded nucleic acid and GTP. It was suggested, therefore, that this protein might be part of a nucleoprotein complex and could function as a GTP-dependent translation factor.
Mammalian Co-A dehydrogenases (
) are enzymes that catalyse the first step in each cycle of beta-oxidation in mitochondion. Acyl-CoA dehydrogenases [
,
,
] catalyze the alpha,beta-dehydrogenation of acyl-CoA thioesters to the corresponding trans 2,3-enoyl CoA-products with concommitant reduction of enzyme-bound FAD. Reoxidation of the flavin involves transfer of electrons to ETF (electron transfering flavoprotein) []. These enzymes are homodimers containing one molecule of FAD.
Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [
,
,
,
,
]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few []. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target. This entry represents MIZ-type zinc finger domains. Miz1 (Msx-interacting-zinc finger) is a zinc finger-containing protein with homology to the yeast protein, Nfi-1. Miz1 is a sequence specific DNA binding protein that can function as a positive-acting transcription factor. Miz1 binds to the homeobox protein Msx2, enhancing the specific DNA-binding ability of Msx2 [
]. Other proteins containing this domain include the human pias family (protein inhibitor of activated STAT protein).
Members of this family are NAD kinases
. The enzymes catalyse the phosphorylation of NAD to NADP utilizing ATP and other nucleoside triphosphates, as well as inorganic polyphosphate, as a source of phosphorus. Such enzymes are thus designated poly(P)/ATP-NAD kinases [
]. NAD kinase is one of the key enzymes regulating the cellular NADP(H) level, and therefore NADPH-dependent reductive biosynthetic pathways [].
ATP-NAD kinases (
) catalyse the phosphorylation of NAD to NADP utilizing ATP and other nucleoside triphosphates as well as inorganic polyphosphate as a source of phosphorus. ATP-NAD kinase contains two domains, where the N-terminal domain has an alpha/beta topology that is related in structure to the N-terminal of phosphofructokinase, and the C-terminal domain has an atypical β-sandwich topology made of four structural repeats of beta(3) units [
,
]. This entry represents the all-beta C-terminal domain.
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 M10 (clan MA(M)).
The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA.Sequences having this domain are extracellular metalloproteases, such as collagenase and stromelysin, which
degrade the extracellular matrix, are known as matrixins. They are zinc-dependent,calcium-activated proteases synthesised as inactive precursors
(zymogens), which are proteolytically cleaved to yield the active enzyme[
,
]. All matrixins and related proteins possess 2 domains: an N-terminaldomain, and a zinc-binding active site domain. The N-terminal domain
peptide, cleaved during the activation step, includes a conserved PRCGVPDVoctapeptide, known as the cysteine switch, whose Cys residue chelates the
active site zinc atom, rendering the enzyme inactive [
,
]. The active enzymedegrades components of the extracellular matrix, playing a role in the
initial steps of tissue remodelling during morphogenesis, wound healing,angiogenesis and tumour invasion [
,
].
The MEROPS peptidase family M10, subfamily M10A, consists of extracellular metalloproteases, such as collagenase and stromelysin, that degrade the extracellular matrix and are known as matrixins or matrix metalloproteinases (MMPs). They are zinc-dependent, calcium-activated proteases synthesised as inactive precursors(zymogens), which are proteolytically cleaved to yield the active enzyme [,
].All matrixins and related proteins possess two domains: an N-terminal
domain, and a zinc-binding active site domain. The N-terminal domainpeptide, cleaved during the activation step, includes a conserved PRCGVPDV
octapeptide, known as the cysteine switch, whose Cys residue chelates theactive site zinc atom, rendering the enzyme inactive [
,
]. The active enzyme degrades components of the extracellular matrix, playing a role in the initial steps of tissue remodelling during morphogenesis, wound healing, angiogenesis and tumour invasion [,
]. Although it was initially thought that the primary function of these enzymes is to degrade proteins of the extracellular matrix, MMPs have a much broader spectrum of activity that includes the proteolytic processing of cytokines, growth factors, growth factor receptors, and cell adhesion molecules [,
].
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 [].The majority of zinc-dependent metallopeptidases (with the notable exception
of the carboxypeptidases) share a common pattern ofprimary structure [
,
]
in the part of their sequence involved in the binding of zinc, and can begrouped together as a superfamily,known as the metzincins, on the basis of
this sequence similarity. They can be classified into around 40 distinct families []. This signature defines the metallopeptidases associated with MEROPS peptidase families: M7, M8, M10 (subfamilies A, B and C) and M12 (subfamily A) all of which are members of clan MA(M).
HPC2 (Histone promoter control 2) is required for cell-cycle regulation of histone transcription [
]. It regulates transcription of the histone genes during the S-phase of the cell cycle by repressing transcription at other cell cycle stages. HPC2 mutants display synthetic interactions with FACT complex which allows RNA Pol II to elongate through nucleosomes []. This short domain is referred to as the HRD or Hpc2-related domain and is found in both human, yeast and Sch. pombe sequences. Hpc2 is one of the proteins of one of the multi-subunit complexes that mediate replication-independent nucleosome assembly, along with histone chaperone proteins. The Hip4 sequence from Sch. pombe is an integral component of this complex that is required for transcriptional silencing at multiple loci [
].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].Ribosomal protein L2 is one of the proteins from the large ribosomal subunit. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities [
], groups:Eubacterial L2.Algal and plant chloroplast L2.Cyanelle L2.Archaebacterial L2.Plant L2.Slime mold L2.Marchantia polymorpha mitochondrial L2.Paramecium tetraurelia mitochondrial L2.Fission yeast K5, K37 and KD4.Yeast YL6.Vertebrate L8.This entry represents the ribosomal protein L2 from archaea. All members belong to the L2P family.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [,
].Ribosomal protein L2 is one of the proteins from the large ribosomal subunit. The best conserved region is located in the C-terminal section of these proteins. In Escherichia coli, L2 is known to bind to the 23S rRNA and to have peptidyltransferase activity. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities [
], groups:Eubacterial L2.Algal and plant chloroplast L2.Cyanelle L2.Archaebacterial L2.Plant L2.Slime mold L2.Marchantia polymorpha mitochondrial L2.Paramecium tetraurelia mitochondrial L2.Fission yeast K5, K37 and KD4.Yeast YL6.Vertebrate L8.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].This superfamily represents domain 3 of the ribosomal protein L2 from the large 50S subunit. The 50S subunit proteins function primarily to stabilise inter-domain interactions that are necessary to maintain the subunit's structural integrity, displaying a wide variety of protein-RNA interactions. This domain has an irregular structure [
].
This is the N-terminal domain found in proteins from plants, yeast and humans, including 25S rRNA (uridine-N(3))-methyltransferase BMT5 from S. cerevisiae and the poorly characterised Ferredoxin-fold anticodon-binding domain-containing protein 1 from human and Heavy metal-associated isoprenylated plant protein 41 from Arabidopsis. This domain has a characteristic Rossmann-like fold of S-adenosyl-L-methionine (SAM) binding domains [
]. BTM5 is a SAM-dependent methyltransferase that specifically methylates the N3 position of uridine in 25S rRNA.
Thaumatin [
] is an intensely sweet-tasting protein, 100,000 times sweeter than sucrose on a molar basis [] found in berries from Thaumatococcus daniellii, a tropical flowering plant known as Katemfe, it is induced by attack by viroids, which are single-stranded unencapsulated RNA molecules that do not code for protein.Thaumatin consists of about 200 residues and contains 8 disulphide bonds. Like other PR proteins, thaumatin is predicted to have a mainly beta structure, with a high content of β-turns and little helix [
]. Several stress-induced proteins of plants have been found to be related to thaumatins: A maize alpha-amylase/trypsin inhibitorTwo tobacco pathogenesis-related proteins: PR-R major and minor forms,which are induced after infection with viruses Salt-induced protein NP24 from tomatoOsmotin, a salt-induced protein from tobacco [
]
Osmotin-like proteins OSML13, OSML15 and OSML81 from potato [
]
P21, a leaf protein from soybeanPWIR2, a leaf protein from wheat [
]
Zeamatin, a maize antifungal protein [
]
This protein is also referred to as pathogenesis-related group 5 (PR5), as many thaumatin-like proteins accumulate in plants in response to infection by a pathogen and possess antifungal activity [
]. The proteins are involved in systematically acquired resistance and stress responses in plants, although their precise role is unknown [].This entry represents a conserved site that includes three cysteine residues known to be involved in disulphide bonds.
This entry represents a short (30 residues) domain of unknown function found in a family of fungal proteins. It contains a characteristic DLL sequence motif.
Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP. There are several different types of transmembrane ATPases, which can differ in function (ATP hydrolysis and/or synthesis), structure (e.g., F-, V- and A-ATPases, which contain rotary motors) and in the type of ions they transport [
,
]. The different types include:F-ATPases (ATP synthases, F1F0-ATPases), which are found in mitochondria, chloroplasts and bacterial plasma membranes where they are the prime producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts).V-ATPases (V1V0-ATPases), which are primarily found in eukaryotes and they function as proton pumps that acidify intracellular compartments and, in some cases, transport protons across the plasma membrane []. They are also found in bacteria [].A-ATPases (A1A0-ATPases), which are found in Archaea and function like F-ATPases, though with respect to their structure and some inhibitor responses, A-ATPases are more closely related to the V-ATPases [
,
].P-ATPases (E1E2-ATPases), which are found in bacteria and in eukaryotic plasma membranes and organelles, and function to transport a variety of different ions across membranes.E-ATPases, which are cell-surface enzymes that hydrolyse a range of NTPs, including extracellular ATP.This entry represent eukaryotic V-ATPase 116kDa subunit (also known as subunit a). V-ATPase is a heteromultimeric enzyme composed of a peripheral catalytic V1 complex (components A to H) attached to an integral membrane V0 proton pore complex [
]. V-ATPase 116kDa subunit is part of the integral membrane V0 complex of vacuolar ATPase and is essential for assembly and catalytic activity [,
]. V-ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells.
Prephenate dehydratase (
, PDT) catalyses the decarboxylation of prephenate to phenylpyruvate. In microorganisms it is part of the terminal pathway of phenylalanine biosynthesis. In some bacteria such as Escherichia coli PDT is part of a bifunctional enzyme (P-protein) that also catalyses the transformation of chorismate into prephenate (chorismate mutase,
,
) while in other bacteria it is a monofunctional enzyme. In the archaea Archaeoglobus fulgidus is part of a trifunctional enzyme [
]. The sequence of monofunctional PDT aligns well with the C-terminal part of P-proteins [].This entry represents two conserved regions. The first contains a conserved threonine which appears to be essential for the activity of the enzyme in E. coli [
]. The second region is located in the regulatory (Phe binding) region in the part C-terminal to PDT and this includes a conserved glutamate.
Prephenate dehydratase (
, PDT) catalyses the decarboxylation of prephenate to phenylpyruvate. In microorganisms it is part of the terminal pathway of phenylalanine biosynthesis. In some bacteria such as Escherichia coli PDT is part of a bifunctional enzyme (P-protein) that also catalyses the transformation of chorismate into prephenate (chorismate mutase,
,
) while in other bacteria it is a monofunctional enzyme. In the archaea Archaeoglobus fulgidus is part of a trifunctional enzyme [
]. The sequence of monofunctional PDT aligns well with the C-terminal part of P-proteins [].The prephenate dehydratase domain is also found in the six PDT-like homologues of Arabidopsis. They use arogenate more efficiently than prephenate, and consequently they have been classified as arogenate dehydratases [
].
Vps53 complexes with Vps52 and Vps54 to form a multi-subunit complex called Golgi-Associated Retrograde Protein complex (GARP) involved in retrograde transport from early and late endosomes to late Golgi [
,
,
]. They are members of the CATCHR (complexes associated with tethering containing helical rods) which includes the exocyst, COG, GARP, and DSL1 complexes which have structural and functional similarities. This is the N-terminal coiled-coil domain [].
Tetraspanins are a distinct family of cell surface proteins, containing four conserved transmembrane domains: a small outer loop (EC1), a larger outer loop (EC2), a small inner loop (IL) and short cytoplasmic tails. They contain characteristic structural features, including 4-6 conserved extracellular cysteine residues, and polar residues within transmembrane domains. A fundamental role of tetraspanins appears to be organising other proteins into a network of multimolecular membrane microdomains, sometimes called the 'tetraspanin web'. Within this web there are primary complexes in which tetraspanins show robust, specific, and direct lateral associations with other proteins. The strong tendency of tetraspanins to associate with each other probably contributes to the assembly of a network of secondary interactions in which non-tetraspanin proteins are associated with each other via palmitoylated tetraspanins acting as linker proteins. In addition, the association of lipids, such as gangliosides and cholesterol, probably contributes to the assembly of even larger tetraspanin complexes, which have some lipid raft-like properties (e.g. resistance to solubilization in non-ionic detergents). Within the tetraspanin web, tetraspanin proteins can associate not only with integrins and other transmembrane proteins, but also with signalling enzymes such as protein kinase C and phosphatidylinositol-4 kinase. Thus, the tetraspanin web provides a mechanistic framework by which membrane protein signalling can be expanded into a lateral dimension [].
Cytoskeleton-associated proteins (CAPs) are involved in the organisation of microtubules and transportation of vesicles and organelles along the cytoskeletal network. A conserved glycine-rich domain, CAP-Gly, has been identified in a number of CAPs, including CLIP-170 and dynactins. The crystal structure of the Caenorhabditis elegans F53F4.3 protein CAP-Gly domain has been solved. The domain contains three β-strands. The most conserved sequence, GKNDG, is located in two consecutive sharp turns on the surface, forming the entrance to a groove [
].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].Ribosomal protein S12 is one of the proteins from the small ribosomal subunit.
In Escherichia coli, S12 is known to be involved in the translation initiationstep. It is a very basic protein of 120 to 150 amino-acid residues. S12
belongs to a family of ribosomal proteins which are grouped on the basis of sequencesimilarities. This protein is known typically as S12 in bacteria, S23 in eukaryotes and as either S12 or S23 in the Archaea.Bacterial S12 molecules contain a conserved aspartic acid residue which undergoes a novel post-translational modification, beta-methylthiolation, to form the corresponding 3-methylthioaspartic acid.
This family consists of plant root hair defective 3 (RHD3) protein and its homologues from other eukaryotes. RHD3 is a conserved protein with GTP-binding motifs that is implicated in the control of vesicle trafficking between the endoplasmic reticulum and the Golgi compartments [
] and is also involved in homotypic ER membrane fusion, being classified as a dynamin-like GTPase together with its homologues Sey1 and atlastin []. It is required for appropriate root and root hair cells enlargement []. It may play a role in cell wall biosynthesis and actin organisation [,
]. Its homologue from Saccharomyces cerevisiae, Sey1, mediates homotypic ER fusion [,
].
The glycine-tyrosine-phenylalanine (GYF) domain is an around 60-amino acid domain which contains a conserved GP[YF]xxxx[MV]xxWxxx[GN]YF motif. It was identified in the human intracellular protein termed CD2 binding protein 2 (CD2BP2), which binds to a site containing two tandem PPPGHR segments within the cytoplasmic region of CD2. Binding experiments and mutational analyses have demonstrated the critical importance of the GYF tripeptide in ligand binding. A GYF domain is also found in several other eukaryotic proteins of unknown function []. It has been proposed that the GYF domain found in these proteins could also be involved in proline-rich sequence recognition [].Resolution of the structure of the CD2BP2 GYF domain by NMR spectroscopy revealed a compact domain with a β-β-α-β-beta topology, where the single α-helix is tilted away from the twisted, anti-parallel β-sheet. The conserved residues of the GYF domain create a contiguous patch of predominantly hydrophobic nature which forms an integral part of the ligand-binding site [
]. There is limited homology within the C-terminal 20-30 amino acids of various GYF domains, supporting the idea that this part of the domain is structurally but not functionally important [].
This entry represents the N-terminal domain of GBF1-interacting protein 1 (GIP1, AT3G13222) from Arabidopsis. GIP1 may act as a coactivator that regulates transcription factors involved in lateral organ development of plants, such as bZIP transcription factors and LBD18 [
,
].
Mg2+ transporter protein, CorA-like/Zinc transport protein ZntB
Type:
Family
Description:
This entry includes prokaryotic magnesium transport protein CorA and its related protein, zinc transport protein ZntB [
]. This entry also includes eukaryotic magnesium transporters, such as mitochondrial inner membrane magnesium transporter Mrs2 and magnesium transporter Alr1 and Alr2. These proteins are characterised by the conserved GMN motif at the end of the first of twoconserved transmembrane (TM) domains near the C terminus [
]. Thermotoga maritima CorA (TmCorA) has been reported to be an efflux system. It only has 2 TM domains,TM1 and TM2 [
,
,
]. The loop connecting TM1 and TM2 contains the conserved CorA signature motifs YGMNF and MPEL. With its N- and C-terminal ends face the cytosol and its similarity to the class II CorA (a CorA group lacking the MPEL motif and may transport divalent cations out of the cell), TmCorA is predicted to be primarily involved in ion efflux []. It forms a pentameric membrane protein channel featuring a possible ion discriminating aspartate ring at the cytoplasmic entrance of the pore and two distinct cytoplasmic metal binding sites per monomer, which could have regulatory roles [,
]. It has been suggested that eukaryotic CorA homologues have the same topology and overall structure as T. maritima CorA [
]. In budding yeasts, Mrs2 is an essential component of the major electrophoretic Mg2+ influx system in mitochondria []. Overexpression of Alr1 or Alr2 increases tolerance to Al3+ and Ga3+ ions []. Despite generally low sequence similarity, both human Mrs2 (also known as LPE10) and S. typhimurium CorA can restore Mg2+ uptake activity in Saccharomyces cerevisiae with inactive Mrs2 [].
This entry consists of the mitochondrial 39S ribosomal protein L28, mitochondrial 54S ribosomal protein L24 and 50S ribosomal protein L28. They belong to the ribosomal protein L28 family. They are components of the mitochondrial or non-mitochondrial large ribosomal subunits.Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].The ribosomal L28 protein family include proteins from bacteria
and chloroplasts. The L24 protein from yeast, found in the large subunit of the mitochodrial ribosome, contains a region similar to the bacterial L28 protein.
The Macro or A1pp domain is a module of about 180 amino acids which can bind ADP-ribose (an NAD metabolite) or related ligands. Binding to ADP-ribose could be either covalent or non-covalent [
]: in certain cases it is believed to bind non-covalently []; while in other cases (such as Aprataxin) it appears to bind both non-covalently through a zinc finger motif, and covalently through a separate region of the protein []. The domain was described originally in association with ADP-ribose 1''-phosphate (Appr-1''-P) processing activity (A1pp) of the yeast YBR022W protein []. The domain is also called Macro domain as it is the C-terminal domain of mammalian core histone macro-H2A [,
]. Macro domain proteins can be found in eukaryotes, in (mostly pathogenic) bacteria, in archaea and in ssRNA viruses, such as coronaviruses [,
], Rubella and Hepatitis E viruses. In vertebrates the domain occurs e.g. in histone macroH2A, in predicted poly-ADP-ribose polymerases (PARPs) and in B aggressive lymphoma (BAL) protein. The macro domain can be associated with catalytic domains, such as PARP, or sirtuin. The Macro domain can recognise ADP-ribose or in some cases poly-ADP-ribose, which can be involved in ADP-ribosylation reactions that occur in important processes, such as chromatin biology, DNA repair and transcription regulation []. The human macroH2A1.1 Macro domain binds an NAD metabolite O-acetyl-ADP-ribose []. The Macro domain has been suggested to play a regulatory role in ADP-ribosylation, which is involved in inter- and intracellular signaling, transcriptional regulation, DNA repair pathways and maintenance of genomic stability, telomere dynamics, cell differentiation and proliferation, and necrosis and apoptosis. The 3D structure of the SARS-CoV Macro domain has a mixed α/β fold consisting of a central seven-stranded twisted mixed β-sheet sandwiched between two α-helices on one face, and three on the other. The final α-helix, located on the edge of the central β-sheet, forms the C terminus of the protein [
]. The crystal structure of AF1521 (a Macro domain-only protein from Archaeoglobus fulgidus) has also been reported and compared with other Macro domain containing proteins. Several Macro domain only proteins are shorter than AF1521, and appear to lack either the first strand of the β-sheet or the C-terminal helix 5. Well conserved residues form a hydrophobic cleft and cluster around the AF1521-ADP-ribose binding site [,
,
,
].
