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 [
,
].L27 is a protein from the large (50S) subunit; it is essential for ribosome function, but its exact role is unclear. It belongs to a family of ribosomal proteins, examples of which are found in bacteria, chloroplasts of plants and red algae and the mitochondria of fungi (e.g. MRP7 from yeast mitochondria). The schematic relationship between these groups of proteins is shown below.Bacterial L27 Nxxxxxxxxx
Algal L27 NxxxxxxxxxPlant L27 tttttNxxxxxxxxxxxxx
Yeast MRP7 tttNxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx't': transit peptide.
'N': N-terminal of mature protein.
Aldehydes are produced as intermediates during the metabolism of many different compounds including amino acids, carbohydrates, lipids vitamins and steroids [
]. They are highly reactive compounds whose buildup to excess levels can cause cytotoxic, genotoxic and carcinogenic effects. Aldehyde dehydrogenases oxidise these compounds to their respective carboxylic acids. This is necessary both for the operation of these metabolic pathways, and to prevent the concentration of aldehydes within the cell from reaching toxic levels.Proteins in this entry are NAD(P)-dependent aldehyde dehydrogenases, found in a variety of organisms, including general aldehyde dehydrogensases (
), fatty aldehyde dehydrogenases (
), and coniferyl aldehyde dehydrogenase (
). Structural studies of the Rattus norvegicus protein (
) show that this enzyme is a homodimer where each subunit consists of two α-β-alpha domains [
]. The mode of NAD binding differs substantially from that commonly associated with the Rossman fold.Not all enzymes in this family are dehydrogenases. The family also includes beta-apo-4'-carotenal oxygenase from
Neurospora crassawhich is required for the final step in the synthesis of the carotenoid pigment neurosporaxanthin by oxidising beta-apo-4'-carotenal [
]; and 4,4'-diapolycopene aldehyde oxidase from Methylomonaswhich is required for the biosynthesis of a C30 carotenoid dialdehyde pigment [
].
Plant S-receptor kinase-like genes have diverse functions in cell signalling, development, stress responses and host-pathogen defence responses [
].This entry contains receptor-like kinases, including S-locus receptor kinase (SRK). SRK is the female determinant of the self-incompatibility (SI) response in Brassica [
,
]. Flowering plants apply a self-incompatibility mechanism to prevent inbreeding and thereby increase genetic diversity []. In most flowering plants, SI systems are controlled by a single multi-allelic locus termed the S-locus. Other members of this group do not play a role in SI [], and some members are from self-compatible plants such as Oryza sativa (Rice) and Arabidopsis thaliana (Mouse-ear cress), neither of which possess the SI response. and
from Brassica oleracea (Wild cabbage), as well as
from A. thaliana, are reported to possibly have overlapping roles in both defence and development [
,
].The proteins in this family contain an extracellular D-mannose-binding lectin domain (
), an S-locus glycoprotein family domain (
), a PAN domain, and an intracellular kinase domain (
).
Microtubules are polymers of tubulin, a dimer of two 55kDa subunits,
designated alpha and beta [,
]. Within the microtubule lattice, α-βheterodimers associate in a head-to-tail fashion, giving rise to microtubule
polarity. Fluorescent labelling studies have suggested that tubulin isoriented in microtubules with beta-tubulin toward the plus end [
]. For maximal rate and extent of polymerisation into microtubules, tubulin
requires GTP. Two molecules of GTP are bound at different sites, termed N and E. At the E (Exchangeable) site, GTP is hydrolysed during incorporation
into the microtubule. Close to the E site is an invariant region rich in glycine residues, which is found in both chains and is thought to control
access of the nucleotide to its binding site []. Most species, excepting simple eukaryotes, express a variety of closely
related alpha- and beta-isotypes. A third family member, gamma tubulin, hasalso been identified in a number of species [
].British type familial amyloidosis is an autosomal dominant disease
characterised by progressive dementia, spastic paralysis and ataxia. Amyloid deposits from the brain tissue of an individual who died with this
disease have been characterised. Trypsin digestion and subsequent N-terminalsequence analysis yielded a number of short sequences, all of which are
tryptic fragments of the C-termini of human alpha- and beta-tubulin []. Consistent with the definition of amyloid, synthetic peptides based on the
sequences of these fragments formed fibrils in vitro, suggesting that theC-termini of both alpha- and beta-tubulin are closely associated with theamyloid deposits of this type of amyloidosis [
].This entry represents beta tubulin.
In yeast, Yos1 is a subunit of the Yip1p-Yif1p complex and is required for transport between the endoplasmic reticulum and the Golgi complex [
]. This entry also includes animal IER3IP1 (immediate Early Response 3 Interacting Protein 1), which is localized to the endoplasmic reticulum. Mutations in the IER3IP1 gene cause permanent neonatal diabetes mellitus in human [
].
Type II restriction endonucleases (
) are components of prokaryotic DNA restriction-modification mechanisms that protect the organism against invading foreign DNA. These site-specific deoxyribonucleases catalyse the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. Of the 3000 restriction endonucleases that have been characterised, most are homodimeric or tetrameric enzymes that cleave target DNA at sequence-specific sites close to the recognition site. For homodimeric enzymes, the recognition site is usually a palindromic sequence 4-8 bp in length. Most enzymes require magnesium ions as a cofactor for catalysis. Although they can vary in their mode of recognition, many restriction endonucleases share a similar structural core comprising four β-strands and one α-helix, as well as a similar mechanism of cleavage, suggesting a common ancestral origin [
]. However, there is still considerable diversity amongst restriction endonucleases [,
]. The target site recognition process triggers large conformational changes of the enzyme and the target DNA, leading to the activation of the catalytic centres. Like other DNA binding proteins, restriction enzymes are capable of non-specific DNA binding as well, which is the prerequisite for efficient target site location by facilitated diffusion. Non-specific binding usually does not involve interactions with the bases but only with the DNA backbone []. This superfamily represents the core structure found in most type II restriction endonucleases, consisting of a 3-layer α/β/α topology with mixed β-sheets. This core structure can be found in the restriction endonucleases EcoRI, EcoRV, BamHI, BglI, BglII, BstyI, PvuII, MunI, NseI, NgoIV, BsobI, HincII, MspI, FokI (C-terminal), EcoO109IR, as well as in lamba exonuclease, DNA mismatch repair protein MutH, VSR (very short repair) endonucleases, TnsA endonucleases (N-terminal), endonucleases I (Holliday junction resolvase), Hjc-like enzymes, XPF/Rad1/Mus81 nucleases, RecB and RecC exodeoxyribonuclease V (C-terminal), and RecU-like enzymes.
This entry represents a structural domain found in several DNA repair nucleases, such as Rad1, XPF and crossover junction endonucleases EME1 and Mus81 [
,
]. The XPF/Rad1/Mus81-dependent nuclease family specifically cleaves branched structures generated during DNA repair, replication, and recombination, and is essential for maintaining genome stability. The nuclease domain architecture exhibits remarkable similarity to those of restriction endonucleases.
This entry represents the adenylation domain of the mRNA capping enzyme [
]. The mRNA-capping enzyme is composed of two separate chains alpha and beta, respectively a mRNA guanylyltransferase and an RNA 5'-triphosphatase []. Binding of the enzyme to nucleotides is specific to the GMP moiety of GTP. The viral mRNA capping enzyme is a monomer that transfers a GMP cap onto the end of mRNA that terminates with a 5'-diphosphate tail.It contains a catalytic core composed of an adenylation domain and a C-terminal OB-fold domain containing conserved sequence motifs. The adenylation domain binds ATP and contains many active site residues [,
].
This domain is found at the C terminus of the mRNA capping enzyme. The mRNA capping enzyme in yeasts is composed of two separate chains: alpha a mRNA
guanyltransferase and beta an RNA 5'-triphosphate. X-ray crystallography reveals a large conformational change during guanyl transfer by mRNA capping enzymes [
].Binding of the enzyme to nucleotides is specific to the GMP moiety of GTP. The viral
mRNA capping enzyme is a monomer that transfers a GMP cap onto the end of mRNA that terminates with a 5'-diphosphate tail.
This entry represents bifunctional mRNA-capping enzymes that exhibit RNA 5'-triphosphatase activity (
) in the N-terminal region and mRNA guanylyltransferase activity (
) in the C-terminal region [
]. These enzymes catalyse the first two steps of cap formation via the following steps:Removing the gamma-phosphate from the 5'-triphosphate end of nascent mRNA to yield a diphosphate end.Followed by the transfer of the gmp moiety of GTP to the 5'-diphosphate terminus.
This region contains the extracellular repeat that is found in up to seven copies in alpha integrins and related proteins. It forms a 7-fold repeat that adopts a β-propeller structure [
]. The repeat is called the FG-GAP repeat after two conserved motifs in the repeat []. The FG-GAP repeats are found in the N terminus of integrin alpha chains, a region that has been shown to be important for ligand binding []. A putative Ca2+ binding motif is found in some of the repeats. These repeats are found in multiple proteins from eukaryotes and bacteria and mediate diverse biological processes at both molecular and cellular levels, such as cell-cell interactions, host patogen recognition or innate immune responses.
The Josephin domain is an eukaryotic protein module of about 180 residues,
which occurs in stand-alone form in Josephin-like proteins, and as an amino-terminal domain associated with two or three copies of the ubiquitin-
interacting motif (UIM) in ataxin 3-like proteins. Josephin domain-containing proteins function as de-ubiquitination enzymes []. Although it has originally been proposed that the Josephin domain could be an all-alpha helical domain distantly related to ENTH and VHS domains involved in membrane trafficking and regulatory adaptor function [], it is now believed that it is a mainly alpha helical cysteine-protease domain predicted to be active against ubiquitin chains or related substrates [,
].The Josephin domain contains two conserved histidines and one cysteine that is required for the ubiquitin protease activity [
,
] and two ubiquitin-binding sites [].Some proteins known to contain a Josephin domain are:Animal Machado-Joseph disease protein 1 (Ataxin 3). It interacts with key
regulators (CBP, p300 and PCAF) of transcription and repressestranscription.Plant Machado-Joseph disease-like protein (MJD1a-like) (Ataxin 3 homologue).Mammalian Josephin 1 and 2.Drosophila melanogaster Josephin-like protein.Arabidopsis thaliana Josephin-like protein.
Ribulose bisphosphate carboxylase, large subunit, ferrodoxin-like N-terminal
Type:
Domain
Description:
Ribulose bisphosphate carboxylase (RuBisCO) [
,
] catalyses the initial step in Calvin's reductive pentose phosphate cycle in plants as well as purple and green bacteria. It catalyzes the primary CO2 fixation step. Rubisco is activated by carbamylation of an active site lysine, stabilized by a divalent cation, which then catalyzes the proton abstraction from the substrate ribulose 1,5 bisphosphate (RuBP) and leads to the formation of two molecules of 3-phosphoglycerate [,
].
Some oxygen-dependent oxidoreductases are flavoproteins that contains a
covalently bound FAD group which is attached to a histidine via an 8-alpha-(N3-histidyl)-riboflavin linkage. These proteins include:(R)-6-hydroxynicotine oxidase (EC 1.5.3.6) (6-HDNO) [
], a bacterial enzymethat catalyzes the oxygen-dependent degradation of 6-hydroxynicotine into
6-hydroxypyrid-N-methylosmine.Plant reticuline oxidase (EC 1.21.3.3) [
] (berberine-bridge-formingenzyme), an enzyme that catalyzes the oxidation of (S)-reticuline into (S)-
scoulerine in the pathway leading to benzophenanthridine alkaloids.L-gulonolactone oxidase (EC 1.1.3.8) (l-gulono-gamma-lactone oxidase) [
],a mammalian enzyme which catalyzes the oxidation of L-gulono-1,4-lactone to
L-xylo-hexulonolactone which spontaneously isomerizes to L-ascorbate.D-arabinono-1,4-lactone oxidase (EC 1.1.3.24) (L-galactonolactone oxidase),
a yeast enzyme involved in the biosynthesis of D-erythroascorbic acid [].Mitomycin radical oxidase [
], a bacterial protein involved in mitomycinresistance and that probably oxidizes the reduced form of mitomycins.
Cytokinin oxidase (EC 1.4.3.18), a plant enzyme.Rhodococcus fascians fasciation locus protein fas5.This entry represents the conserved region around the histidine that binds the FAD group is conserved in these enzymes.
In Escherichia coli the TonB protein interacts with outer membrane receptor proteins that carry out high-affinity binding and energy-dependent uptake of specific substrates into the periplasmic space [
]. These substrates are either poorly permeable through the porin channels or are encountered at very low concentrations. In the absence of TonB, these receptors bind their substrates but do not carry out active transport. TonB-dependent regulatory systems consist of six components: a specialised outer membrane-localized TonB-dependent receptor (TonB-dependent transducer) that interacts with its energizing TonB-ExbBD protein complex, a cytoplasmic membrane-localized anti-sigma factor and an extracytoplasmic function (ECF)-subfamily sigma factor [
]. The TonB complex senses signals from outside the bacterial cell and transmits them via two membranes into the cytoplasm, leading to transcriptional activation of target genes. The proteins that are currently known or presumed to interact with TonB include BtuB [], CirA, FatA, FcuT, FecA [], FhuA [], FhuE, FepA [], FptA, HemR, IrgA, IutA, PfeA, PupA and Tbp1. The TonB protein also interacts with some colicins. Most of these proteins contain a short conserved region at their N terminus [].This entry represents the plug domain, which has been shown to be an independently folding subunit of the TonB-dependent receptors [
]. It acts as the channel gate, blocking the pore until the channel is bound by a ligand. At this point it undergoes conformational changes and opens the channel.
This superfamily represents domains with a carbohydrate-binding-like fold, which consists of a seven-stranded β-sandwich with a Greek key topology, although some members may have 1-2 extra strands. These domains are present as carbohydrate-binding modules in a number of glycosyl hydrolases, often at the C-terminal end, as well as in rhamnogalacturonase B (RhgB), where it occurs as a central domain [
,
].
A carbohydrate-binding module (CBM) is defined as a contiguous amino acid sequence within a carbohydrate-active enzyme with a discreet fold having carbohydrate-binding activity. A few exceptions are CBMs in cellulosomal scaffolding proteins and rare instances of independent putative CBMs. The requirement of CBMs existing as modules within larger enzymes sets this class of carbohydrate-binding protein apart from other non-catalytic sugar binding proteins such as lectins and sugar transport proteins.CBMs were previously classified as cellulose-binding domains (CBDs) based on the initial discovery of several modules that bound cellulose [
,
]. However, additional modules in carbohydrate-active enzymes are continually being found that bind carbohydrates other than cellulose yet otherwise meet the CBM criteria, hence the need to reclassify these polypeptides using more inclusive terminology.Previous classification of cellulose-binding domains were based on amino acid similarity. Groupings of CBDs were called "Types"and numbered with roman numerals (e.g. Type I or Type II CBDs). In keeping with the glycoside hydrolase classification, these groupings are now called families and numbered with Arabic numerals. Families 1 to 13 are the same as Types I to XIII. For a detailed review on the structure and binding modes of CBMs see [
].This entry represents
, which binds starch. The crystal structure of CBM20 has been solved [
]. It consists of seven β-strands forming an open-sided distorted β-barrel. Several aromatic residues, especially the well-conserved Trp and Tyr residues, participate in granular starch binding.
Complex II [succinate dehydrogenase (succinate-ubiquinone oxidoreductase); SDH] is the only enzyme shared by both the electron transport chain and the tricarboxylic acid (TCA) cycle in mitochondria. In plants, this complex is considered unusual because it has accessory subunits (SDH5-SDH8), in addition to the catalytic subunits of SDH found in all eukaryotes (SDH1-SDH4) [].This family represents the accessory complex II subunit Succinate dehydrogenase subunit 5, mitochondrial from plants [
,
].
Alcohol dehydrogenase (
) (ADH) catalyzes the reversible oxidation of ethanol to acetaldehyde with the concomitant reduction of NAD:
Ethanol + NAD = Acetaldehyde + NADH
Currently three structurally and catalytically different types of alcohol dehydrogenases are known:Zinc-containing 'long-chain' alcohol dehydrogenases.Insect-type, or 'short-chain' alcohol dehydrogenases.Iron-containing alcohol dehydrogenases.Zinc-containing ADH's [,
] are dimeric or tetrameric enzymes that bind twoatoms of zinc per subunit. One of the zinc atom is essential for catalytic
activity while the other is not. Both zinc atoms are coordinated by eithercysteine or histidine residues; the catalytic zinc is coordinated by two
cysteines and one histidine. Zinc-containing ADH's are found in bacteria,mammals, plants, and in fungi. In most species there are more than one isozyme
(for example, human have at least six isozymes, yeast have three, etc.). A
number of other zinc-dependent dehydrogenases are closely related to zincADH [
] and are included in this family, includingxylitol dehydrogenase (
); sorbitol dehydrogenase (
);
aryl-alcohol dehydrogenase (); threonine 3-dehydrogenase (
); cinnamyl-alcohol dehydrogenase (
) (CAD);
galactitol-1-phosphate dehydrogenase (); and Pseudomonas putida 5-exo-alcohol dehydrogenase (
).
Haem oxygenase (
) (HO) [
] is the microsomal enzyme that, in animals, carries out the oxidation of haem, it cleaves the haem ring at the alpha-methene bridge to form biliverdin and carbon monoxide []. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. In mammals there are three isozymes of haem oxygenase: HO-1 to HO-3. The first two isozymes differ in their tissue expression and their inducibility: HO-1 is highly inducible by its substrate haem and by various non-haem substances, while HO-2 is non-inducible. It has been suggested [] that HO-2 could be implicated in the production of carbon monoxide in the brain where it is said to act as a neurotransmitter. In the genome of the chloroplast of red algae as well as in cyanobacteria, there is a haem oxygenase (gene pbsA) that is the key enzyme in the synthesis of the chromophoric part of the photosynthetic antennae []. A haem oxygenase is also present in the bacteria Corynebacterium diphtheriae (gene hmuO), where it is involved in the acquisition of iron from the host haem []. There is, in the central section of these enzymes, a well-conserved region centred on a histidine residue.
This superfamily represents a multi-helical structural domain consisting of two structural repeats (duplication) of a 3-helical motif. This domain can be found in both eukaryotic and prokaryotic haem oxygenases [
,
], in TENA/THI-4 proteins that lack the haem-binding site [], and in coenzyme PQQ (pyrrolo-quinoline-quinone) biosynthesis protein C (PqqC) [].Haem oxygenase (
) (HO) is the microsomal enzyme that, in animals, carries out the oxidation of haem, cleaving the haem ring at the alpha-methene bridge to form biliverdin and carbon monoxide. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. In mammals there are three isozymes of haem oxygenase: HO-1 to HO-3. The first two isozymes differ in their tissue expression and their inducibility: HO-1 is highly inducible by its substrate haem and by various non-haem substances, while HO-2 is non-inducible. Haem oxygenase is also present in certain bacteria, where it is involved in the acquisition of iron from the host haem.
The THI-4 protein is involved in thiamine biosynthesis, while TENA is one of a number of proteins that enhance the expression of extracellular enzymes, such as alkaline protease, neutral protease and levansucrase.Coenzyme PQQ (pyrrolo-quinoline-quinone) biosynthesis protein C (PqqC;
) is required for the synthesis of PQQ, where PQQ is a prosthetic group found in several bacterial enzymes, including methanol dehydrogenase of methylotrophs and the glucose dehydrogenase of a number of bacteria.
This domain is found at the C-terminal of the fungal protein D-arabinono-1,4-lactone oxidase
, which is involved in the final step of the biosynthesis pathway of D-erythroascorbic acid, an important antioxidant and one of the virulence factors [
,
].L-gulonolactone oxidase transforms L-gulono-1,4-lactone to L-xylo-hexulonolactone, which spontaneously isomerizes to L-ascorbate. This enzyme can be found in a range of organisms from chordates and plants to Mycobacteria [
,
,
].Alditol oxidase from Streptomyces coelicolor also belong to this family. It performs selective oxidation of the terminal primary hydroxyl group of several alditols [
].
This domain is involved in binding sterols, and is found in proteins such as SCP2. This domain has a 3-layer alpha/beta/alpha fold, composed of alpha/beta(3)/(crossover)/beta/(alpha)/beta. The human sterol carrier protein 2 (SCP2), also known as nonspecific lipid transfer protein, is a basic protein that is believed to participate in the intracellular transport of cholesterol and various other lipids [
]. The Unc-24 protein of Caenorhabditis elegans contains a domain similar to part of two ion channel regulators (the erythrocyte integral membrane protein stomatin and the C. elegans neuronal protein MEC-2) juxtaposed to a domain similar to nonspecific lipid transfer protein (nsLTP; also called sterol carrier protein 2) [].
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.Alpha-amylases, which belong to glycoside hydrolase family 13, are 1,4-alpha-D-glucan glucanohydrolases, which degrade both the branched and unbranched forms of starch by cleaving the
internal alpha-1,4 bonds connecting the glucose monomers. The products ofthese reactions are maltose and maltotriose, which are further degraded to
glucose by maltases. One atom of calcium is required to bind to each proteinmolecule to allow it to function, but excess calcium can inhibit activity
by binding to amino acids that are required for the catalytic activityof the enzyme.
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.Alpha-amylase is classified as family 13 of the glycosyl hydrolases and is present in archaea, bacteria, plants and animals. Alpha-amylase is an essential enzyme in alpha-glucan metabolism, acting to catalyse the hydrolysis of alpha-1,4-glucosidic bonds of glycogen, starch and related polysaccharides. Although all alpha-amylases possess the same catalytic function, they can vary with respect to sequence. In general, they are composed of three domains: a TIM barrel containing the active site residues and chloride ion-binding site (domain A), a long loop region inserted between the third beta strand and the α-helix of domain A that contains calcium-binding site(s) (domain B), and a C-terminal β-sheet domain that appears to show some variability in sequence and length between amylases (domain C) [
]. Amylases have at least one conserved calcium-binding site, as calcium is essential for the stability of the enzyme. The chloride-binding functions to activate the enzyme, which acts by a two-step mechanism involving a catalytic nucleophile base (usually an Asp) and a catalytic proton donor (usually a Glu) that are responsible for the formation of the beta-linked glycosyl-enzyme intermediate. This entry represents the β-sheet domain that is found in several alpha-amylases, usually at the C terminus. This domain is organised as a five-stranded anti-parallel β-sheet [
,
].
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.Alpha-amylase is classified as family 13 of the glycosyl hydrolases and is present in archaea, bacteria, plants and animals. Alpha-amylase is an essential enzyme in alpha-glucan metabolism, acting to catalyse the hydrolysis of alpha-1,4-glucosidic bonds of glycogen, starch and related polysaccharides. Although all alpha-amylases possess the same catalytic function, they can vary with respect to sequence. In general, they are composed of three domains: a TIM barrel containing the active site residues and chloride ion-binding site (domain A), a long loop region inserted between the third beta strand and the α-helix of domain A that contains calcium-binding site(s) (domain B), and a C-terminal β-sheet domain that appears to show some variability in sequence and length between amylases (domain C) [
]. Amylases have at least one conserved calcium-binding site, as calcium is essential for the stability of the enzyme. The chloride-binding functions to activate the enzyme, which acts by a two-step mechanism involving a catalytic nucleophile base (usually an Asp) and a catalytic proton donor (usually a Glu) that are responsible for the formation of the beta-linked glycosyl-enzyme intermediate. This entry represents a subfamily of alpha-amylase proteins that are found in plants.
Mutations in the lipin gene lead to fatty liver dystrophy in mice. The protein has been shown to be phosphorylated by the TOR Ser/Thr protein kinases in response to insulin stimulation. This entry represents a conserved domain found at the N terminus of the member proteins [
,
].
This domain is found in lipins and lipin homologues from Saccharomyces cerevisiae (Smp2) and from Schizosaccharomyces pombe (Ned1) [
]. Smp2 (also known as PAH1) is involved in plasmid maintenance and respiration [] and has been identified as a Mg2+-dependent phosphatidate phosphatase () that contains a haloacid dehalogenase (HAD)-like domain [
]. Lipin proteins are phosphatidate phosphatases which catalyse the dephosphorylation of phosphatidic acid to diacylglycerol, the penultimate step in triacylglycerol synthesis []. They are involved in adipose tissue development and insulin resistance [].
DNA-directed DNA polymerase, family A, palm domain
Type:
Domain
Description:
Synonym(s): DNA nucleotidyltransferase (DNA-directed)
DNA-directed DNA polymerases(
) are the key enzymes catalysing the accurate replication of DNA. They require either a small RNA molecule or a protein as a primer for the
de novosynthesis of a DNA chain. A number of polymerases belong to this family [
,
,
].
DNA carries the biological information that instructs cells how to exist in an ordered fashion. Accurate replication is thus one of the most important events in the cell life cycle. This function is mediated by DNA-directed DNA polymerases, which add nucleotide triphosphate (dNTP) residues to the 3'-end of the growing DNA chain, using a complementary DNA as template. Small RNA molecules are generally used as primers for chain elongation, although terminal proteins may also be used. DNA-dependent DNA polymerases have been grouped into families, denoted A, B and X, on the basis of sequence similarities [
,
]. Members of family A, which includes bacterial and bacteriophage polymerases, share significant similarity to Escherichia coli polymerase I; hence family A is also known as the pol I family. The bacterial polymerases also contain an exonuclease activity, which is coded for in the N-terminal portion. Three motifs, A, B and C [], are seen to be conserved across all DNA polymerases, with motifs A and C also seen in RNA polymerases. They are centred on invariant residues, and their structural significance was implied from the Klenow (E. coli) structure. Motif A contains a strictly-conserved aspartate at the junction of a β-strand and an α-helix; motif B contains an α-helix with positive charges; and motif C has a doublet of negative charges, located in a β-turn-beta secondary structure [].This entry represents the DNA-polymerase A family.
This entry represents selenoprotein T (SelT), which is conserved from plants to humans. SelT is localized to the endoplasmic reticulum through a hydrophobic domain. The protein binds to UDP-glucose:glycoprotein glucosyltransferase (UGTR), the endoplasmic reticulum (ER)-resident protein, which is known to be involved in the quality control of protein folding [
,
]. Selenium (Se) plays an essential role in cell survival and most of the effects of Se are probably mediated by selenoproteins, including selenoprotein T. The function of SelT is unknown, although it may have a role in PACAP signaling during PC12 cell differentiation [,
].
This entry represents the Rdx family of selenoproteins, which includes mammalian selenoproteins SelW, SelV, SelT and SelH, bacterial SelW-like proteins and cysteine-containing proteins of unknown function in all three domains of life. Mammalian Rdx12 and its fish selenoprotein orthologues are also members of this family [
]. These proteins possess a thioredoxin-like fold and a conserved CXXC or CxxU (U is selenocysteine) motif near the N terminus, suggesting a redox function. Rdx proteins can use catalytic cysteine (or selenocysteine) to form transient mixed disulphides with substrate proteins. Selenium (Se) plays an essential role in cell survival and most of the effects of Se are probably mediated by selenoproteins. Selenoprotein W (SelW) plays an important role in protection of neurons from oxidative stress during neuronal development [
], []. Selenoprotein T (SelT) is conserved from plants to humans. SelT is localized to the endoplasmic reticulum through a hydrophobic domain. The protein binds to UDP-glucose:glycoprotein glucosyltransferase (UGTR), the endoplasmic reticulum (ER)-resident protein, which is known to be involved in the quality control of protein folding [
,
]. The function of SelT is unknown, although it may have a role in PACAP signaling during PC12 cell differentiation [,
]. Selenoprotein H (SelH) protects neurons against UVB-induced damage by inhibiting apoptotic cell death pathways, by preventing mitochondrial depolarization, and by promoting cell survival pathways [
].
Accurate transcription initiation at protein-coding genes by RNA polymerase II requires the assembly of a multiprotein complex around the mRNA start site. Transcription factor TFIID is one of the general factors involved in this process. Yeast TFIID comprises the TATA binding protein and 14 TBP-associated factors (TAFIIs), nine of which contain histone-fold domains. The C-terminal region of the TFIID-specific yeast TAF4 (yTAF4) containing the HFD shares strong sequence similarity with Drosophila (d)TAF4 and human TAF4. A structure/function analysis of yTAF4 demonstrates that the HFD, a short conserved C-terminal domain (CCTD), and the region separating them are all required for yTAF4 function. This region of similarity is found in Transcription initiation factor TFIID component TAF4 [
]. TAF4 domain interacts with TAF12 and makes a novel histone-like heterodimer that binds DNA and has a core promoter function of a subset of genes [
,
,
].
This entry represents a domain found in eukaryotic sialic acid acetylesterases (SIAEs). The catalytic triad of this esterase enzyme comprises residues Ser127, His403 and Asp391 in mouse SIAE [
,
]. Proteins containing this domain also include some uncharacterised bacterial proteins.
Glycoside hydrolase family 20 (
) comprises enzymes with several known activities; beta-hexosaminidase (
); lacto-N-biosidase (
); beta-1,6-N-acetylglucosaminidase); and beta-6-SO3-N-acetylglucosaminidase. Carbonyl oxygen of the C-2 acetamido group of the substrate acts as the catalytic nucleophile/base in this family of enzymes [
].This entry represents the glycoside hydrolase family 20 catalytic domain. This domain has a TIM barrel fold.
Augmin is a protein complex required for centrosome-independent microtubule generation within the spindle [
]. In plants, which lack a centrosome structure, an augmin complex also exists. The plant augmin complex contains eight subunits []. This family consist of AUGMIN subunit 7.
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.
Interferon-related developmental regulator (IFRD1) is the human homologue of the Rattus norvegicus early response protein PC4 and its murine homologue TIS7 [
]. IFRD1 is a transcriptional coactivator/repressor controlling patterns of gene expression by interacting with transcription factors or histone deacetylase (HDAC) complexes []. This entry also contains IFRD2 and its murine equivalent SKMc15, which are highly expressed soon after gastrulation and in the hepatic primordium, suggesting an involvement in early hematopoiesis [].
Small hydrophilic plant seed protein, conserved site
Type:
Conserved_site
Description:
This entry represents a conserved site in hydrophilic plant seed proteins that are structurally related:Arabidopsis thaliana proteins GEA1 and GEA6Cotton late embryogenesis abundant (LEA) protein D-19Carrot EMB-1 proteinBarley LEA proteins B19.1A, B19.1B, B19.3 and B19.4Maize late embryogenesis abundant protein Emb564Radish late seed maturation protein p8B6Rice embryonic abundant protein Emp1Sunflower 10 Kd late embryogenesis abundant protein (DS10)Wheat Em proteinsThese proteins may play a role in equipping the seed for survival, maintaining a minimal level of hydration in the dry organism and preventing the denaturation of cytoplasmic components [
,
]. They may also play a role during imbibition by controlling water uptake.
This entry contains the plant LEA (late embryogenesis abundant) proteins, which are small hydrophilic plant seed proteins that are structurally related.
These proteins contains from 83 to 153 amino acid residues and may play a role[
,
] in equipping the seed for survival, maintaining a minimal level ofhydration in the dry organism and preventing the denaturation of cytoplasmic
components. They may also play a role during imbibition by controlling wateruptake.
AMP-deaminase (AMPD) (
) is a large, well-conserved eukaryotic protein that catalyzes the hydrolytic deamination of adenosine monophosphate (AMP) to inosine monophosphate (IMP), and so plays an important role in purine metabolism. In mammalian liver, the reaction catalysed by AMP-deaminase constitutes a rate-limiting step in adenine nucleotide catabolism [
]. Not all members of the family are active enzymes: YBR284W and YJL070C lack residues for binding the catalytic zinc ion, and YJL070C lacks substrate binding residues.
Spen (split end) proteins regulate the expression of key transcriptional effectors in diverse signalling pathways. They are large proteins characterised by N-terminal RNA-binding motifs and a highly conserved C-terminal SPOC (Spen paralog and ortholog C-terminal) domain. The function of the SPOC domain is unknown, but the SPOC domain of the SHARP Spen protein has been implicated in the interaction of SHARP with the SMRT/NcoR corepressor, where SHARP plays an essential role in the repressor complex [
].The SPOC domain is folded into a single compact domain consisting of a β-barrel with seven strands framed by six alpha helices. A number of deep grooves and clefts in the surface, plus two nonpolar loops, render the SPOC domain well suited to protein-protein interactions; most of the conserved residues occur on the protein surface rather than in the core. Other proteins containing a SPOC domain include Drosophila Split ends, which promotes sclerite development in the head and restricts it in the thorax, and mouse MINT (homologue of SHARP), which is involved in skeletal and neuronal development via its repression of Msx2.
Ran is an evolutionary conserved member of the Ras superfamily that regulates all receptor-mediated transport between the nucleus and the cytoplasm. Ran Binding Protein 1 (RanBP1) has guanine nucleotide dissociation inhibitory activity, specific for the GTP form of Ran and also functions to stimulate Ran GTPase activating protein(GAP)-mediated GTP hydrolysis by Ran. RanBP1 contributes to maintaining the gradient of RanGTP across the nuclear envelope high (GDI activity) or the cytoplasmic levels of RanGTP low (GAP cofactor) [
].All RanBP1 proteins contain an approx 150 amino acid residue Ran binding domain. Ran BP1 binds directly to RanGTP with high affinity.
There are four sites of contact between Ran and the Ran binding domain. One of these involves binding of the C-terminal segment of Ran to a groove on the Ran binding domain that is analogous to the surface utilised in the EVH1-peptide interaction []. Nup358 contains four Ran binding domains. The structure of the first of these is known [].
Proteins of this family have been identified in a number of species as a nuclear protein with a cell cycle dependence. Various names have been given to members of this family which include cell cycle protein p38-2G4, also known as proliferation-associated protein PA2G4 [
,
], curved DNA-binding protein [], proliferation-associated protein A, and ErbB3-binding protein 1 (Ebp1) []. They constitute the proliferation-associated PA2G4 family, which is structurally homologous to the type II methionine aminopeptidases, but without methionine aminopeptidase activity [,
]. ErbB3 binding protein-1 (Ebp1) is a potential regulator of ErbB3 signaling, and is implicated in cell growth, apoptosis and differentiation in many cell types [,
].These proteins are classified as non-peptidase homologues in the MEROPS peptidase family M24 (clan MG).
Transaldolase (
) catalyses the reversible transfer of a three-carbon ketol unit from sedoheptulose 7-phosphate to glyceraldehyde 3-phosphate to form erythrose 4-phosphate and fructose 6-phosphate. This enzyme, together with transketolase, provides a link between the glycolytic and pentose-phosphate pathways. Transaldolase is an enzyme of about 34kDa whose sequence has been well conserved throughout evolution. A lysine has been implicated [
] in the catalytic mechanism of the enzyme; it acts as a nucleophilic group that attacks the carbonyl group of fructose-6-phosphate.This entry represents transaldolases type 2, which is found in bacteria and plants.
Transaldolase (TAL) is an enzyme of the pentose phosphate pathway (PPP) found almost ubiquitously in the three domains of life (Archaea, Bacteria, and Eukarya). TAL shares a high degree of structural similarity and sequence identity with fructose-6-phosphate aldolase (FSA) [
]. They both belong to the class I aldolase family []. Their protein structures have been revealed [].Transaldolase (
) catalyses the reversible transfer of a three-carbon ketol unit from sedoheptulose 7-phosphate to glyceraldehyde 3-phosphate to form erythrose 4-phosphate and fructose 6-phosphate. This enzyme, together with transketolase, provides a link between the glycolytic and pentose-phosphate pathways. Transaldolase is an enzyme of about 34kDa whose sequence has been well conserved throughout evolution. A lysine has been implicated [
] in the catalytic mechanism of the enzyme; it acts as a nucleophilic group that attacks the carbonyl group of fructose-6-phosphate.Fructose-6-phosphate aldolase was originally thought to be transaldolases or transaldolase-related proteins. However, they perform a novel reaction, the cleavage or formation of fructose 6-phosphate [
].
The STAT protein (Signal Transducers and Activators of Transcription) family contains transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors, hence they act as signal transducers in the cytoplasm and transcription activators in the nucleus [
]. Binding of these factors to cell-surface receptors leads to receptor autophosphorylation at a tyrosine, the phosphotyrosine being recognised by the STAT SH2 domain, which mediates the recruitment of STAT proteins from the cytosol and their association with the activated receptor. The STAT proteins are then activated by phosphorylation via members of the JAK family of protein kinases, causing them to dimerise and translocated to the nucleus, where they bind to specific promoter sequences in target genes. In mammals, STATs comprise a family of seven structurally and functionally related proteins: Stat1, Stat2, Stat3, Stat4, Stat5a and Stat5b, Stat6. STAT proteins play a critical role in regulating innate and acquired host immune responses. Dysregulation of at least two STAT signalling cascades (i.e. Stat3 and Stat5) is associated with cellular transformation.Signalling through the JAK/STAT pathway is initiated when a cytokine binds to its corresponding receptor. This leads to conformational changes in the cytoplasmic portion of the receptor, initiating activation of receptor associated members of the JAK family of kinases. The JAKs, in turn, mediate phosphorylation at the specific receptor tyrosine residues, which then serve as docking sites for STATs and other signalling molecules. Once recruited to the receptor, STATs also become phosphorylated by JAKs, on a single tyrosine residue. Activated STATs dissociate from the receptor, dimerise, translocate to the nucleus and bind to members of the GAS (gamma activated site) family of enhancers.The seven STAT proteins identified in mammals range in size from 750 and 850 amino acids. The chromosomal distribution of these STATs, as well as the identification of STATs in more primitive eukaryotes, suggest that this family arose from a single primordial gene. STATs share 6 structurally and functionally conserved domains including: an N-terminal domain (ND) that strengthens interactions between STAT dimers on adjacent DNA-binding sites; a coiled-coil STAT domain (CCD) that is implicated in protein-protein interactions; a DNA-binding domain (DBD) with an immunoglobulin-like fold similar to p53 tumour suppressor protein; an EF-hand-like linker domain connecting the DNA-binding and SH2 domains; an SH2 domain (
) that acts as a phosphorylation-dependent switch to control receptor recognition and DNA-binding; and a C-terminal transactivation domain [
,
,
]. The crystal structure of the N terminus of Stat4 reveals a dimer. The interface of this dimer is formed by a ring-shaped element consisting of five short helices. Several studies suggest that this N-terminal dimerisation promotes cooperativity of binding to tandem GAS elements and with the transcriptional coactivator CBP/p300.
Barwin is a basic protein isolated from aqueous extracts of barley seeds. It is
125 amino acids in length, and contains six cysteine residues that combine to formthree disulphide bridges [
,
]. Comparative analysis shows the sequence to be highly similar to a 122 amino acid stretch in the C-terminal of the products of two wound-induced genes (win1 and win2) from potato, the product of the hevein gene of rubber trees, and pathogenesis-related protein 4 from tobacco. The high levels of similarity to these proteins, and their ability to bind saccharides, suggest that the barwin domain may be involved in a common defence mechanism in plants.
Glycosylphosphatidylinositol anchor biosynthesis protein Pig-F is involved in glycosylphosphatidylinositol (GPI) anchor biosynthesis [
,
,
]. This family also includes the Pif-F homologue GPI11 (glycosylphosphatidylinositol anchor biosynthesis protein 11) []. It is involved in the ethanolamine-phosphate transfer-step of GPI biosynthesis [].
This domain, found at the C terminus of tRNA(Met) cytidine acetyltransferase, may be involved in tRNA-binding [
]. tRNA(Met) cytidine acetyltransferase TmcA catalyses the formation of N(4)-acetylcytidine (ac4C) at the wobble position of tRNA(Met), by using acetyl-CoA as an acetyl donor and ATP (or GTP) [].
This entry represents a domain found in the N terminus of the bacterial tRNA(Met) cytidine acetyltransferase TmcA. TmcA catalyses the formation of N(4)-acetylcytidine (ac4C) at the wobble position of tRNA(Met), by using acetyl-CoA as an acetyl donor and either ATP or GTP [
]. This modification is thought to ensure precise recognition of the AUG codon by strengthening C-G base-pair interaction and also prevent misrecognition of the near cognate AUA codon []. This domain can also be found in mammalian N-acetyltransferase 10 (NAT10) and fungal protein Kre33. Kre33 and NAT10 are RNA cytosine acetyltransferases with specificity toward both 18S rRNA and tRNAs [
,
].
This domain contains a P-loop (Walker A) motif, suggesting that it has ATPase activity, and a Walker B motif. In tRNA(Met) cytidine acetyltransferase (TmcA) it may function as an RNA helicase motor (driven by ATP hydrolysis) which delivers the wobble base to the active centre of the GCN5-related N-acetyltransferase (GNAT) domain [
]. It is found in the bacterial exodeoxyribonuclease V alpha chain (RecD), which has 5'-3' helicase activity. It is structurally similar to the motor domain 1A in other SF1 helicases [
].
This entry consists of several plant wound-induced protein sequences related to WI12 from Mesembryanthemum crystallinum (Common ice plant) (
). Wounding, methyl jasmonate, and pathogen infection is known to induce local WI12 expression. WI12 expression is also thought to be developmentally controlled in the placenta and developing seeds. WI12 preferentially accumulates in the cell wall and it has been suggested that it plays a role in the reinforcement of cell wall composition after wounding and during plant development [
].
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 a family of conserved proteins which were originally described as death-associated-protein-3 (DAP-3). The proteins carry a P-loop DNA-binding motif, and induce apoptosis [
]. DAP3 has been shown to be a pro-apoptotic factor in the mitochondrial matrix [] and to be crucial for mitochondrial biogenesis and so has also been designated as MRP-S29 (mitochondrial ribosomal protein subunit 29).
Ribokinases participate in the first step of ribose metabolism, and are members of the superfamily of carbohydrate kinases. Ribokinases phosphorylate ribose to ribose-5-phosphate in the presence of ATP and magnesium [
]:ATP + D-Ribose = ADP + D-Ribose-5-Phosphate
The phosphorylated sugar may then enter the pentose phosphate pathway [
]. There are indications that the phosphorylated sugar may also be used in the synthesis of amino acids (histidine and tryptophan). Further, links to mammalian adenosine kinase have been identified, through sequence similarity, suggesting possible homology [,
].This family also includes fructokinases [
]. Fructokinase may be involved in a sugar-sensing pathway in plants [,
].Other proteins included in this entry are: cytidine kinase from Thermococcus kodakarensis [
], Sulfofructose kinase from Escherichia coli [], Pseudouridine kinase from Arabidopsis thaliana [] and MJ0406 () from Methanocaldococcus jannaschii. MJ0406 was previously annotated as a 6-phosphofructokinases (PFK), but has since been characterised as a functional nucleoside kinase [
].
Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [
,
,
,
,
]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few []. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target. This entry represents the HIT-type zinc finger, which contains 7 conserved cysteines and one histidine that can potentially coordinate two zinc atoms. It has been named after the first protein that originally defined the domain: the yeast HIT1 protein (
) [
]. The HIT-type zinc finger displays some sequence similarities to the MYND-type zinc finger. The function of this domain is unknown but it is mainly found in nuclear proteins involved in gene regulation and chromatin remodeling. This domain is also found in the thyroid receptor interacting protein 3 (TRIP-3) , that specifically interacts with the ligand binding domain of the thyroid receptor.
N-acetyltransferase B complex, non-catalytic subunit
Type:
Family
Description:
This is the non-catalytic subunit of the N-terminal acetyltransferase B complex (NatB). The NatB complex catalyses the acetylation of the amino-terminal methionine residue of all proteins beginning with Met-Asp or Met-Glu and of some proteins beginning with Met-Asn or Met-Met. In Saccharomyces cerevisiae (Baker's yeast) this subunit is called MDM20 and in Schizosaccharomyces pombe (Fission yeast) it is called Arm1. NatB acetylates the Tpm1 protein and regulates and tropomyocin-actin interactions. This subunit is required by the NatB complex for the N-terminal acetylation of Tpm1 [
].
This domain is characterised by two well-conserved short regions separated by a variable region in both sequence and length. The first of the two regions is found in a large number of proteins outside this group, a number of which have been characterised as methyltransferases. One member of this group, FkbM, was shown to be required for a specific methylation in the biosynthesis of the immunosuppressant FK506 in Streptomyces strain MA6548 [].This domain is also found in other methyltransferases such as SdnD from the fungus Sordaria araneosa, involved in the biosynthesis of glycoside antibiotics with tetracyclic diterpene aglycone structure [
] and in AMB antimetabolite synthase AmbE from Pseudomonas aeruginosa, which participates in the biosynthesis of the antimetabolite L-2-amino-4-methoxy-trans-3-butenoic acid (AMB), a non-proteinogenic amino acid which is toxic for prokaryotes and eukaryotes [,
].
Enzymes like bacterial malonyl CoA-acly carrier protein transacylase (
) and eukaryotic fatty acid synthase (
) that are involved in fatty acid biosynthesis belong to this group [
]. Also included are the polyketide synthases 6-methylsalicylic acid synthase (), a multifunctional enzyme that involved in the biosynthesis of patulin and conidial green pigment synthase (
) and several non-reducing polyketide synthases.
Enzymes like bacterial malonyl CoA-acly carrier protein transacylase (
) and eukaryotic fatty acid synthase (
) that are involved in fatty acid biosynthesis belong to this group [
]. Also included are the polyketide synthases 6-methylsalicylic acid synthase (), a multifunctional enzyme that involved in the biosynthesis of patulin and conidial green pigment synthase (
) and several non-reducing polyketide synthases.
Phosphatidate cytidylyltransferase (
) [
,
,
] (also known as CDP-diacylglycerol synthase) (CDS) is the enzyme that catalyzes the synthesis of
CDP-diacylglycerol from CTP and phosphatidate (PA):CTP + phosphatidate = diphosphate + CDP-diacylglycerol
CDP-diacylglycerol is animportant branch point intermediate in both prokaryotic and eukaryotic
organisms. CDS is a membrane-bound enzyme.
Slx1 is a catalytic subunit of the SLX1-SLX4 structure-specific endonuclease that resolves DNA secondary structures generated during DNA repair and recombination. It has endonuclease activity towards branched DNA substrates, introducing single-strand cuts in duplex DNA close to junctions with ss-DNA [
,
,
].
Nucleases of the GIY-YIG family are involved in many cellular processes, including DNA repair and recombination, transfer of mobile genetic elements, and restriction of incoming foreign DNA. The GIY-YIG superfamily groups together nucleases characterised by the presence of a domain of typically ~100 amino acids, with two short motifs "GIY"and "YIG"in the N-terminal part, followed by an Arg residue in the centre and a Glu residue in the C-terminal part [
,
,
,
,
]. The GIY-YIG domain forms a compact structural domain, which serves as a scaffold for the coordination of a divalent metal ion required for catalysis of the phosphodiester bond cleavage. The GIY-YIG domain has an α/β-sandwich architecture with a central three-stranded antiparallel β-sheet flanked by three-helices. The three-stranded antiparallel β-sheet contains the GIY-YIG sequence elements. The most conserved and putative catalytic residues are located on a shallow, concave surface and include a metal coordination site [
,
,
,
].The GIY-YIG domain has been implicated in a variety of cellular processes involving DNA cleavage, from self-propagation with or without introns, to restriction of foreign DNA, to DNA repair and maintenance of genome stability [
]. Some proteins known to contain a GIY-YIG domain include:Eukaryotic Slx-1 proteins, involved in the maintenance of the rDNA copy number. They have a C-terminal RING finger Zn-binding domain.Mammalian ankyrin repeat and LEM domain- containing protein 1 (ANKLE1).Bacterial and archaeal UvrC subunits of (A)BC excinucleases, which remove damaged nucleotides by incising the damaged strand on both sides of the lesion.Phage T4 endonucleases SegA to E, probably involved in the movement of the endonuclease-encoding DNA.Phage T4 intron-associated endonuclease 1 (I-TevI), specific to the thymidylate synthase (td) gene splice junction and involved in intron homing.
Transcription initiation factor TFIID is a multimeric protein complex that
plays a central role in mediating promoter responses to various activatorsand repressors. The complex includes TATA binding protein (TBP) and various
TBP-associated factors (TAFS). TFIID is a bona fide RNA polymerase II-specificTATA-binding protein-associated factor (TAF) and is essential for viability [
]. This entry represents one of the TAFs, TAF10.
TFIID acts to nucleate the transcription complex, recruiting the rest of
the factors through a direct interaction with TFIIB. The TBP subunit of TFIID is sufficient for TATA-element binding and TFIIB interaction, and can support basal transcription. The protein belongs to the TAF2H family.TAF10 is part of other transcription regulatory multiprotein complexes (e.g., SAGA, TBP-free TAF-containing complex [TFTC], STAGA, and PCAF/GCN5). Several TAFs interact via histone-fold motifs. The histone fold (HFD) is the interaction motif involved in heterodimerization of the core histones and their assembly into nucleosome octamer. The minimal HFD contains three α-helices linked by two loops. The HFD is found in core histones, TAFs and many other transcription factors. Five HF-containing TAF pairs have been described in TFIID: TAF6-TAF9, TAF4-TAF12, TAF11-TAF13, TAF8-TAF10 and TAF3-TAF10 [,
,
].
Ferritin is one of the major non-heme iron storage proteins in animals, plants and microorganisms [
,
]. It consistsof a mineral core of hydrated ferric oxide, and a multi-subunit protein shell
which encloses the former and assures its solubility in an aqueousenvironment.
In animals, the protein is mainly cytoplasmic and there are generally two or
more genes that encode closely related subunits (in mammals there are twosubunits which are known as H(eavy) and L(ight)). In plants ferritin is found
in the chloroplast [].This entry represents the central region of this protein.
This entry represents ferritin and structurally related proteins. Ferritin is a major non-haem iron storage protein in animal, plants and microorganisms [
]. Iron is required by most organisms, but is potentially toxic due to its reactivity, which is counteracted by sequestering it into ferritin. Ferritin consists of a 4-helical bundle core, and contains a bimetal-ion centre in the middle of the bundle. Other proteins with this structure include: haem-containing bacteriferritins; rubrerythrin, which appears to have a role in anaerobic detoxification pathway for reactive oxygen species []; Dps (DNA-binding proteins from starved cells) used in bacteria for iron storage-detoxification; and CRD1 (AcsF), which is required for the maintenance of photosystem I [].
Ferritin is one of the major non-haem iron storage proteins in animals, plants, and microorganisms [
]. It consists of a mineral core of hydrated ferric oxide, and a multi-subunit protein shell that encloses the former and assures its solubility in an aqueous environment.In animals the protein is mainly cytoplasmic and there are generally two or more genes that encode closely related subunits - in mammals there are two subunits which are known as H(eavy) and L(ight). In plants ferritin is found in the chloroplast [
].This entry represents the main structural domain of ferritin. The domain is also found in other ferritin-like proteins such as members of the DNA protection during starvation (DPS) family [
] and bacterioferritins [].
Ferritin is one of the major non-haem iron storage proteins in animals, plants, and microorganisms [
,
]. It consists of a mineral core of hydrated ferric oxide, and a multi-subunit protein shell which encloses the former and assures its solubility in an aqueous environment.In animals the protein is mainly cytoplasmic and there are generally two or more genes that encode closely related subunits (in mammals there are two subunits which are known as H(eavy) and L(ight)). In plants ferritin is found in the chloroplast [
].
This entry represents a group of proteins, containing ferritin-like domain, which is an about 145-residue domain made of a four-helix
bundle surrounding a non-heme, non-sulphur, oxo-bridged diiron site. The diiron site is contained within a twisted, left-handed four-helix-bundle constituted of two anti-parallel helix pairs connected through a
left-handed crossover connection. Known ligand residues at non-heme, non-sulphur diiron sites in proteins include His, Asp, Glu, and Tyr. Proteins
containing a ferritin-like diiron domain possess the ability to catalyzeoxidation of Fe
2+to Fe
2+by O
2, i.e. ferroxidase activity. The ferritin-
like diiron domain occurs in stand-alone form in ferritin and bacterioferritinor in association with the rubredoxin-like domain in
rubrerythrin [].Proteins known to contain a ferritin-like diiron domain are listed below:
Ferritin (Ftn), an eukaryotic intracellular protein that stores iron in a
soluble, nontoxic, readily available form.Bacterioferritin (Bfr), a prokaryotic protein which may perform functions
in iron detoxification and storage.Rubrerythrin (Rr), a non-heme protein isolated from anaerobic sulphate-
reducing bacteria.Nigerythrin (Nr), a prokaryotic protein of unknown function.
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 ofthe 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 L11 is one of the proteins from the large ribosomal subunit. In Escherichia coli, L11
is known to bind directly to the 23S rRNA. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities [], groups bacterial, chloroplast, cyanelle, and most mitochondrial forms of ribosomal protein L11. L11 is a protein of 140 to 165 amino-acid residues. In E. coli, the C-terminal half of L11 has been shown [] to be in an extended and loosely folded conformation and is likely to be buried within the ribosomal structure. This entry represents the bacterial, chloroplast and mitochondrial forms.
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 L11 is one of the proteins from the large ribosomal subunit. In Escherichia coli, L11 is known to bind directly to the 23S rRNA and plays a significant role during initiation, elongation, and termination of protein synthesis. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities [
], groups bacteria, plant chloroplast, red algal chloroplast, cyanelle and archaeabacterial L11; and mammalian, plant and yeast L12 (YL15). L11 is a protein of 140 to 165 amino-acid residues. L11 consists of a 23S rRNA binding C-terminal domain and an N-terminal domain that directly contacts protein synthesis factors. These two domains are joined by a flexible linker that allows inter-domain movement during protein synthesis. While the C-terminal domain of L11 binds RNA tightly, the N-terminal domain makes only limited contacts with RNA and is proposed to function as a switch that reversibly associates with an adjacent region of RNA [,
,
,
]. In E. coli, the C-terminal half of L11 has been shown [] to be in an extended and loosely folded conformation and is likely to be buried within the ribosomal structure.
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 L11 is one of the proteins from the large ribosomal subunit. In Escherichia coli, L11 is known to bind directly to the 23S rRNA and plays a significant role during initiation, elongation, and termination of protein synthesis. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities [
], groups bacteria, plant chloroplast, red algal chloroplast, cyanelle and archaeabacterial L11; and mammalian, plant and yeast L12 (YL15). L11 is a protein of 140 to 165 amino-acid residues. L11 consists of a 23S rRNA binding C-terminal domain and an N-terminal domain that directly contacts protein synthesis factors. These two domains are joined by a flexible linker that allows inter-domain movement during protein synthesis. While the C-terminal domain of L11 binds RNA tightly, the N-terminal domain makes only limited contacts with RNA and is proposed to function as a switch that reversibly associates with an adjacent region of RNA [,
,
,
]. In E. coli, the C-terminal half of L11 has been shown [] to be in an extended and loosely folded conformation and is likely to be buried within the ribosomal structure.This entry identifies a conserved region located in the C-terminal section of these proteins.
This family contains Escherichia coli YbhB and YbcL that are possibly RKIP homologues, found in the cytoplasm and periplasm.The crystal structures of YbhB and YbcL demonstrates that they belong to
the same structural family as the mammalian RKIP/PEBP proteins. In rat and human cells, RKIP (previously known as PEBP) has been characterised as an inhibitor of the MEK phosphorylation by Raf-1. The general structural fold and the anion binding site of these proteins are extremely well conserved between mammals and bacteria and suggest functional similarities. However, the bacterial proteins also exhibit some specific structural features, like a substrate binding pocket formed by the dimerisation interface and the absence of cis peptide bonds. The parallel between the cellular signalling mechanisms in eukaryotes and prokaryotes suggests that the proteins in this family could be involved in the regulation of protein phosphorylation by kinases. The structural variety observed for YbhB and YbcL indicates the possible recognition of multiple cellular partners [
].
The PEBP (PhosphatidylEthanolamine-Binding Protein) family is a highly conserved group of proteins that have been identified in numerous tissues in a wide variety of organisms, including bacteria, yeast, nematodes, plants, drosophila and mammals. The various functions described for members of this family include lipid binding, neuronal development [
], serine protease inhibition [], the control of the morphological switch between shoot growth and flower structures [], and the regulation of several signalling pathways such as the MAP kinase pathway [], and the NF-kappaB pathway []. The control of the latter two pathways involves the PEBP protein RKIP, which interacts with MEK and Raf-1 to inhibit the MAP kinase pathway, and with TAK1, NIK, IKKalpha and IKKbeta to inhibit the NF-kappaB pathway. Other PEBP-like proteins that show strong structural homology to PEBP include Escherichia coli YBHB and YBCL, the Rattus norvegicus (Rat) neuropeptide HCNP, and Antirrhinum majus (Garden snapdragon) protein centroradialis (CEN). Structures have been determined for several members of the PEBP-like family, all of which show extensive fold conservation. The structure consists of a large central β-sheet flanked by a smaller β-sheet on one side, and an alpha helix on the other. Sequence alignments show two conserved central regions, CR1 and CR2, that form a consensus signature for the PEBP family. These two regions form part of the ligand-binding site, which can accommodate various anionic groups. The N- and C-terminal regions are the least conserved, and may be involved in interactions with different protein partners. The N-terminal residues 2-12 form the natural cleavage peptide HCNP involved in neuronal development. The C-terminal region is deleted in plant and bacterial PEBP homologues, and may help control accessibility to the active site.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].A number of eukaryotic and archaeal ribosomal proteins can be grouped on the basis of
sequence similarities. One of these families includes yeast S7 (YS6); archaeal S4e; and mammalian and plant cytoplasmic S4 [
]. Two highly similar isoforms of mammalian S4 exist, one coded by a gene on chromosome Y, and the other on chromosome X. These proteins have
233 to 264 amino acids.This entry represents the N-terminal region of these proteins.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].A number of eukaryotic and archaeal ribosomal proteins can be grouped on the basis of
sequence similarities. One of these families includes yeast S7 (YS6); archaeal S4e; and mammalian and plant cytoplasmic S4 [
]. Two highly similar isoforms of mammalian S4 exist, one coded by a gene on chromosome Y, and the other on chromosome X. These proteins have
233 to 264 amino acids.
A number of eukaryotic and archaeal ribosomal proteins can be grouped on the basis of
sequence similarities. One of these families includes yeast S7 (YS6); archaeal S4e; and
mammalian and plant cytoplasmic S4 []. Two highly similar isoforms of mammalian S4 exist, one coded by a gene on chromosome Y, and the other on chromosome X. These proteins have
233 to 264 amino acids.This entry represents the conserved site of the ribosomal protein S4e that is found at the N-terminal region.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].A number of eukaryotic and archaeal ribosomal proteins can be grouped on the basis of
sequence similarities. One of these families includes yeast S7 (YS6); archaeal S4e; and mammalian and plant cytoplasmic S4 [
]. Two highly similar isoforms of mammalian S4 exist, one coded by a gene on chromosome Y, and the other on chromosome X. These proteins have
233 to 264 amino acids.This entry represents the central region of these proteins.
6-Phosphofructo-2-kinase (
,
) is a bifunctional enzyme that catalyses both the synthesis and the degradation of fructose-2, 6-bisphosphate. The fructose-2,6-bisphosphatase reaction involves a phosphohistidine intermediate. The catalytic pathway is:
ATP + D-fructose 6-phosphate = ADP + D-fructose 2,6-bisphosphate
D-fructose 2,6-bisphosphate + H2O = 6-fructose 6-phosphate + P
iThe enzyme is important in the regulation of hepatic carbohydrate metabolism and is found in greatest quantities in the liver, kidney and heart. In mammals, several genes often encode different isoforms, each of which differs in its tissue distribution and enzymatic activity []. The family described here bears a resemblance to the ATP-driven phospho-fructokinases, however, they share little sequence similarity, although a few residues seem key to their interaction with fructose 6-phosphate [].This domain forms the N-terminal region of this enzyme, while
forms the C-terminal domain.
6-Phosphofructo-2-kinase (
,
) is a bifunctional enzyme that catalyses both the synthesis and the degradation of fructose-2, 6-bisphosphate. The fructose-2,6-bisphosphatase reaction involves a phosphohistidine intermediate. The catalytic pathway is:
ATP + D-fructose 6-phosphate = ADP + D-fructose 2,6-bisphosphate
D-fructose 2,6-bisphosphate + H2O = 6-fructose 6-phosphate + P
iThe enzyme is important in the regulation of hepatic carbohydrate metabolism and is found in greatest quantities in the liver, kidney and heart. In mammals, several genes often encode different isoforms, each of which differs in its tissue distribution and enzymatic activity []. The family described here bears a resemblance to the ATP-driven phospho-fructokinases, however, they share little sequence similarity, although a few residues seem key to their interaction with fructose 6-phosphate [].
Gamma interferon inducible lysosomal thiol reductase GILT
Type:
Family
Description:
In humans, GILT (gamma-interferon-inducible lysosomal thiol reductase) functions in MHC class II-restricted antigen processing and MHC class I-restricted cross-presentation by reducing disulfide bonds of endocytosed proteins and facilitating their unfolding and optimal degradation [
,
]. Several other functions of GILT have also been found, for instance, GILT can act as a host factor for Listeria monocytogenes infection and is involved in the maintenance of cellular glutathione (GSH) levels []. GILT is characterised by a CXXC motif in the active site and an enzymatic mechanism in which the pair of active site cysteine residues cooperate to reduce substrate disulfide bonds [
]. The GIL homologues from Drosophila melanogaster may play a role in the innate immune response upon bacterial challenge [].
Members of protein family FAM175 include the BRCA1-A complex subunit Abraxas 1 [
,
], BRISC complex subunit Abraxas 2 or Abro1 (Abraxas brother protein 1) [,
], and uncharacterised plant proteins.It is thought that BRCA1-A complex subunit Abraxas acts as a central scaffold protein responsible for assembling the various components of the BRCA1-A complex, and mediates recruitment of BRCA1 [
,
]. Similarly, Abro1 probably acts as a scaffold facilitating assembly of the various components of BRISC [] - the protein does not interact with BRCA1, but binds polyubiquitin []. The primary sequences of these proteins contain an MPN-like domain [].This entry represents the plant members of FAM175.
Members of protein family FAM175 include the BRCA1-A complex subunit Abraxas 1 [
,
], BRISC complex subunit Abraxas 2 or Abro1 (Abraxas brother protein 1) [,
], and uncharacterised plant proteins.It is thought that BRCA1-A complex subunit Abraxas acts as a central scaffold protein responsible for assembling the various components of the BRCA1-A complex, and mediates recruitment of BRCA1 [
,
]. Similarly, Abro1 probably acts as a scaffold facilitating assembly of the various components of BRISC [] - the protein does not interact with BRCA1, but binds polyubiquitin []. The primary sequences of these proteins contain an MPN-like domain [].
S1FA is an unusual small plant peptide of only 70 amino acids with a basic
domain which contains a nuclear localization signal and a putative DNA binding helix. S1FA is highly conservedbetween dicotyledonous and monocotyledonous plants and may be a DNA-binding protein that specifically recognises the negative promoter element S1F [
].
The Sgf11 (SAGA-associated factor 11) family is a SAGA complex subunit in Saccharomyces cerevisiae (Baker's yeast). The SAGA complex is a multisubunit protein complex involved in transcriptional regulation. SAGA combines proteins involved in interactions with DNA-bound activators and TATA-binding protein (TBP), as well as enzymes for histone acetylation and deubiquitylation [
].
This entry represents a domain found in hydrolase enzymes that belong to the isochorismatase family, including Ureidoacrylate amidohydrolase RutB from Escherichia coli and Nicotinamidase from Saccharomyces cerevisiae. Isochorismatase (also known as 2,3 dihydro-2,3 dihydroxybenzoate synthase) catalyses the conversion of isochorismate, in the presence of water, to 2,3-dihydroxybenzoate and pyruvate [
]. This domain shows a typical helix-sheet-helix sandwich structural architecture, with a central β-sheet made of six parallel strands, three α-helices on one side and two α-helices on the other [].
The post-translational attachment of ubiquitin (
) to proteins (ubiquitinylation) alters the function, location or trafficking of a protein, or targets it to the 26S proteasome for degradation [
,
,
]. Ubiquitinylation is an ATP-dependent process that involves the action of at least three enzymes: a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2, ), and a ubiquitin ligase (E3,
,
), which work sequentially in a cascade [
]. The E1 enzyme is responsible for activating ubiquitin, the first step in ubiquitinylation. The E1 enzyme hydrolyses ATP and adenylates the C-terminal glycine residue of ubiquitin, and then links this residue to the active site cysteine of E1, yielding a ubiquitin-thioester and free AMP. To be fully active, E1 must non-covalently bind to and adenylate a second ubiquitin molecule. The E1 enzyme can then transfer the thioester-linked ubiquitin molecule to a cysteine residue on the ubiquitin-conjugating enzyme, E2, in an ATP-dependent reaction.
Ubiquitin-activating enzyme (E1 enzyme) [
,
] activates ubiquitin by firstadenylating with ATP its C-terminal glycine residue and thereafter linking
this residue to the side chain of a cysteine residue in E1, yielding anubiquitin-E1 thiolester and free AMP. Later the ubiquitin moiety is
transferred to a cysteine residue on one of the many forms of ubiquitin-conjugating enzymes (E2).
E1 is a large monomeric protein of about 110 to 115 Kd (about 1000 residues).
In yeast there are two forms (UBA1 and UBA2) [], while in plants and mammalsmultiple forms exist including a form which is Y-linked in mouse and some
other mammals and which may be involved in spermatogenesis.It has been shown that the last of the five cysteines that are conserved in the sequence of E1 from various species is the one that binds ubiquitin [
]. This entry represents a conserved region containing the second of the five conserved cysteines.
The post-translational attachment of ubiquitin (
) to proteins (ubiquitinylation) alters the function, location or trafficking of a protein, or targets it to the 26S proteasome for degradation [
,
,
]. Ubiquitinylation is an ATP-dependent process that involves the action of at least three enzymes: a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2, ), and a ubiquitin ligase (E3,
,
), which work sequentially in a cascade [
]. The E1 enzyme is responsible for activating ubiquitin, the first step in ubiquitinylation. The E1 enzyme hydrolyses ATP and adenylates the C-terminal glycine residue of ubiquitin, and then links this residue to the active site cysteine of E1, yielding a ubiquitin-thioester and free AMP. To be fully active, E1 must non-covalently bind to and adenylate a second ubiquitin molecule. The E1 enzyme can then transfer the thioester-linked ubiquitin molecule to a cysteine residue on the ubiquitin-conjugating enzyme, E2, in an ATP-dependent reaction.This entry includes Ubiquitin-activating enzyme E1 (Uba1), SUMO-activating enzyme subunit 1 (Sae1) and similar proteins from eukaryotes. Sae1 is an heterodimer that acts as an E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4 and mediates ATP-dependent activation of SUMO proteins [
,
,
].
Proteins of the Ca2+:Cation Antiporter (CaCA) family are found ubiquitously, having been identified in animals, plants, yeast, archaea and widely divergent bacteria. All of the characterised animal proteins catalyze Ca2+:Na+ exchange although some also transport K+. The NCX1 plasma membrane protein exchanges 3 Na+ for 1 Ca2+. The Escherichia coli ChaA protein catalyses Ca2+:H+ antiport but may also catalyze Na+:H+ antiport. All remaining well-characterised members of the family catalyze Ca2+:H+ exchange.
The sodium/calcium exchangers are a family of integral membrane proteins. This domain covers the integral membrane regions of these proteins. Sodium/calcium exchangers regulate intracellular Ca2+ concentrations in many cells; cardiac myocytes, epithelial cells, neurons retinal rod photoreceptors and smooth muscle cells [
]. Ca2+ is moved into or out of the cytosol depending on Na+ concentration []. In humans and rats there are 3 isoforms; NCX1 NCX2 and NCX3 [].
This is a group of calcium/proton exchanger proteins. In Arabidopsis thaliana CAX1 is responsible for maintaining low cytosolic-free Ca2+ concentrations in the plant cells by catalysing pH gradient-energized vacuolar Ca2+ accumulation [
].
This group of proteins have a conserved C-terminal region which is found in LMBR1 and in the lipocalin-1 receptor. LMBR1 was thought to play a role in preaxial polydactyly, but recent evidence now suggests this not to be the case [
]. Vertebrate members of this family may play a role in limb development []. Lysosomal cobalamin transport escort protein LMBD1 is a lysosomal membrane chaperone required to export cobalamin from lysosome to the cytosol, allowing its conversion to cofactors [,
]. This protein showed homology to the lipocalin membrane receptor (LIMR) [].
Tautomerase superfamily members have a (beta-α-β)2 structure in two layers, and use a similar mechanism of action involving an amino-terminal proline as a general base in a ket-enol tautomerisation reaction [
]. Members of this superfamily include macrophage migration inhibitory factor (MIF) and related proteins such as D-dopachrome tautomerase; 4-oxalocrotonoate tautomerase and related enzymes such as trans-3-chloroacrylic acid dehalogenase; and 5-carboxymethyl-2-hydroxymuconate Delta-isomerase (CHMI).Macrophage migration inhibitory factor (MIF) is a key regulatory cytokine within innate and adaptive immune responses, capable of promoting and modulating the magnitude of the response [
]. MIF is released from T-cells and macrophages, and it can regulate cytokine secretion and the expression of receptors involved in the immune response. MIF has been linked to various inflammatory diseases, such as rheumatoid arthritis and atherosclerosis [].4-Oxalocrotonate tautomerase (4-OT) is a plasmid-encoded enzyme that catalyzes the isomerisation of beta,gamma-unsaturated enones to their alpha,beta-isomers. This enzyme is part of the plasmid-encoded catechol meta-fission pathway, which enables the bacteria to use various aromatic hydrocarbons as their sole sources of carbon and energy [
].5-carboxymethyl-2-hydroxymuconate isomerase (CHMI) is a trimeric enzyme involved in the homoprotocatechuate pathway in Escherichia coli [
]. This enzyme catalyses the isomerisation of 5-carboxymethyl-2-hydroxymuconate (CHM) to 5-carboxymethyl-2-oxo-3-hexene-1,6-dioate (COHED).
