Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process.
Protein kinases fall into three broad classes, characterised with respect to substrate specificity []:Serine/threonine-protein kinasesTyrosine-protein kinasesDual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)Protein kinase function is evolutionarily conserved from Escherichia coli to human [
]. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation []. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [].Eukaryotic protein kinases [
,
,
,
,
] are enzymes that belong to a very extensive family of proteins which share a conserved catalytic core common with both serine/threonine and tyrosine protein kinases. There are a number of conserved regions in the catalytic domain of protein kinases.This entry represents a conserved site, which is located in the N-terminal extremity of the catalytic domain, where there is a glycine-rich stretch of residues in the vicinity of a lysine residue. It is this lysine residue that has been shown to be involved in ATP binding.
This domain is found in proteins that are described as 3-ketoacyl-CoA synthases, type III polyketide synthases, fatty acid elongases and fatty acid condensing enzymes, and are found in both prokaryotic and eukaryotic (mainly plant) species. The region contains the active site residues, as well as motifs involved in substrate binding [
].
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 L24 is one of the proteins from the large ribosomal subunit.
L24 belongs to a family of ribosomal proteins which, on the basis of sequencesimilarities, groups:- Eubacterial L24.- Plant chloroplast L24 (nuclear-encoded).- Red algal L24.- Vertebrate L26.- Yeast L26 (YL33).- Archaebacterial HmaL24 (HL15).- A probable ribosomal protein from Sulfolobus acidocaldarius [
].
This domain superfamily can be found in ribosomal protein L2, where it represents domain 2 and it is also found in other ribosomal proteins and in elongation factor P and translation initiation factor 5A , where it constitutes the N-terminal domain [
].
The fundamental activity of the ribosome is two-fold: to decode the message of the mRNA in the small subunit, and to form a peptide bond between peptidyl-tRNA and aminoacyl-tRNA by a peptidyl transferase activity in the large subunit. Several prokaryotic and eukaryotic proteins that are involved in the translation process contain an SH3-like domain. The structure of the translation protein SH3-like domain is a partly opened beta barrel, where the last strand is interrupted by a 3-10 helical turn. The structure of the RNA-binding C-terminal domain of the Bacillus stearothermophilus (Geobacillus stearothermophilus) ribosomal protein L2 has been shown to adopt the SH3-like barrel topology [
]. The L2 protein is located near the peptidyl transferase centre in the large ribosomal subunit where it may contribute to peptidyl transferase activity, and is involved in the assembly of the 23SrRNA. Likewise, the N-terminal domain of the ubiquitous eukaryotic translation elongation factor 5a (IF5A) protein adopts the SH3-like barrel topology [,
]. IF5A, previously thought to be an initiation factor, is now considered to be involved in translation elongation [] and in cell-cycle regulation. IF5A acts as a cofactor of the Rev protein in HIV-1-infected cells and of the Rex protein in T-cell leukaemia virus 1-infected cells.
This entry contains proteins belonging to the UPF0496 family, found in plants. This family includes AT14A like proteins from Arabidopsis thaliana. At14a contains a small domain that has sequence similarities to integrins from fungi, insects and humans. Transcripts of At14a are found in all Arabidopsis tissues and the protein localises partly to the plasma membrane [
].
Ribosomal protein S2 is is a protein of 235 to 394 amino-acid residues and is one of the proteins from the small ribosomal subunit. S2 belongs to a family of ribosomal proteins which, on the basis of sequence similarities [
,
], groups: Eubacterial S2. Algal and plant chloroplast S2. Cyanelle S2. Archaebacterial S2. Higher eukaryotes P40 (previously thought to be a laminin receptor). Yeast NAB1. Plant mitochondrial S2. Yeast mitochondrial MRP4.
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 L3 is one of the proteins from the large ribosomal subunit. In Escherichia coli, L3 is known to bind to the 23S rRNA and may participate in the formation of the peptidyltransferase centre of the ribosome. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities includes bacterial, red algal, cyanelle, mammalian, yeast and Arabidopsis thaliana L3 proteins; archaeal Haloarcula marismortui
HmaL3 (HL1), and yeast mitochondrial YmL9 [,
,
].This entry represents a short conserved region located in the central section of ribosomal L3 proteins.
Cytoplasmic tRNA 2-thiolation protein 1 (also known as Ncs6/Tuc1 in budding yeasts) is responsible for 2-thiolation of mcm5S2U at tRNA wobble positions of tRNA(Lys), tRNA(Glu) and tRNA(Gln) [
,
]. It directly binds tRNAs and probably acts by catalysing adenylation of tRNAs, an intermediate required for 2-thiolation. Its fission yeast homologue, Ctu1 forms a complex with Ctu2 (Ncs2/Tuc2 homologue) and serves as a putative enzyme for the formation of 2-thiouridine []. This family also includes tRNA-5-methyluridine(54) 2-sulfurtransferase, which catalyses the 2-thiolation of 5-methyluridine residue at position 54 in the T loop of tRNAs, leading to 5-methyl-2-thiouridine [].
This entry describes proteins of unknown function. Structures for two of these proteins, YggU from Escherichia coli and MTH637 from the archaea Methanobacterium thermoautotrophicum, have been determined; they have a core 2-layer alpha/beta structure consisting of beta(2)-loop-α-β(2)-alpha [
,
].
This domain is found mainly in plant proteins known as Casparian strip membrane proteins (CASPs). CASPs are four-membrane-span proteins that mediate the deposition of Casparian strips in the endodermis by recruiting the lignin polymerization machinery. Interestingly, the CASP first extracellular loop was found conserved in euphyllophytes but absent in plants lacking Casparian strips [
,
].
A family containing a number of integral membrane proteins is named after TerC protein. TerC has been implicated in resistance to tellurium, and may be involved in efflux of tellurium ions. The tellurite-resistant Escherichia coli strain KL53 was found during testing of a group of clinical isolates for antibiotic and heavy metal ion resistance [
]. The determinant of the strain's tellurite resistance was located on a large conjugative plasmid, and analyses showed the genes terB, terC, terD and terE were essential for conservation of this resistance. Members of this family contain a number of conserved aspartates which may be involved in metal ion binding.A TerC homologue is known from the chloroplast thylakoid membrane from Arabidopsiswhich is important for thylakoid membrane biogenesis in the developing chloroplast [
]; it is required for insertion of proteins into the thylakoid membrane [].This entry represents a subset of TerC proteins which are mostly encoded on genes preceded by a structured RNA element known as the yybP-ykoY leader. The yybP-ykoY leader (also known as SraF) may function in the regulation of these genes as riboswitch [
]. This entry also includes the putative membrane-bound redox modulator Alx [].
Heat shock proteins, Hsp70 chaperones help to fold many proteins. Hsp70 assisted folding involves repeated cycles of substrate binding and release. Hsp70 activity is ATP dependent. Hsp70 proteins are made up of two regions: the amino terminus is the ATPase domain and the carboxyl terminus is the substrate binding region [
].Hsp70 proteins have an average molecular weight of 70kDa [
,
,
]. In most species, there are many proteins that belong to the Hsp70 family. Some of these are only expressed under stress conditions (strictly inducible), while some are present in cells under normal growth conditions and are not heat-inducible (constitutive or cognate) [,
]. Hsp70 proteins can be found in different cellular compartments (nuclear, cytosolic, mitochondrial, endoplasmic reticulum, for example).This entry represents the Hsp70 family, and includes chaperone protein DnaK and luminal-binding proteins. It also includes heat shock protein 110 (Hsp110) from Caenorhabditis elegans which helps prevent the aggregation of denatured proteins in neurons [
]. Also included is endoplasmic reticulum (ER) chaperone BiP (HSPA5) which is important for protein folding and quality control in the ER [].
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.
This entry represents ankyrin repeat domain-containing protein 13 (ANKRD13). At least 4 subtypes are known to exist, termed A-D. ANKRD13C has been experimentally characterised and acts as a chaperone for biogenesis and folding of the DP receptor for prostaglandin D2 [].
The members of this family are hypothetical eukaryotic proteins of unknown function. The region in question is approximately 100 amino acid residues long.
This entry includes AT-hook motif nuclear-localized proteins 15-29 (AHL15-29) from Arabidopsis [
]. They have two conserved structural units, the AT-hook motif and the Plant and Prokaryote Conserved (PPC) domain, the latter also known as DUF296. Members of the AHL family regulate diverse aspects of growth and development in plants []. AHL20 has been shown to negatively regulate defenses in Arabidopsis [].
This family of proteins is found in eukaryotes. Proteins in this family are typically between 81 and 97 amino acids in length. The proteins in the family are often annotated as wound-induced proteins however there is little accompanying literature to confirm this.
Tyrosine specific protein phosphatases (PTPases) (
) contain two conserved cysteines, the second one has been shown to be absolutely required for activity. This entry represents the PTPase domain that centre on the active site cysteine. A number of conserved residues in its immediate vicinity have also been shown to be important. This domain can be found in dual specificity phosphatases.
Dual specificity phosphatases (DUSPs) are members of the superfamily of protein tyrosine phosphatases [
,
]. They remove the phosphate group from both phospho-tyrosine and phospho-serine/threonine residues. They are structurally similar to tyrosine-specific phosphatases but with a shallower active site cleft and a distinctive active site signature motif, HCxxGxxR [,
,
]. They are characterized as VHR- [,
] or Cdc25-like [,
].In general, DUSPs are classified into the following subgroups [
]:Slingshot phosphatasesPhosphatase of regenerating liver (PRL)Cdc14 phosphatasesPhosphatase and tensin homologue deleted on chromosome 10 (PTEN)-like and myotubularin phosphatasesMitogen-activated protein kinase phosphatases (MKPs)Atypical DUSPs
Nematode sperm are unusual amoeboid cells in which motility is not based on actin, but instead on the major sperm protein (MSP). MSP is a dimeric molecule that polymerises to form non-polar filaments constructed from two helical subfilaments that wind round one another. The filaments then assemble into larger macromolecular assemblies called fibre complexes. MSP is a small (~14kDa) basic protein typically encoded by a multigene family of up to 28 members [
,
,
,
]. An about 120-amino acid domain similar to MSP has been found in other proteins, including:Animal Vesicle-Associated Membrane Protein-associated (VAMP-associated) protein family of 33kDa (VAP33). VAP33 is required for neurotransmitter release. It binds to the v-SNARE synaptobrevin/VAMP which is associated with vesicle fusion. VAP33 has a two-domain structure with its N terminus being highly homologous to MSP, whereas its C terminus is based on a putative α-helical coiled-coil combined with an extremely hydrophobic membrane-attachment region [
].Nicotiana plumbaginifolia VAP27, a VAP33 homologue. It interacts with the resistance protein Cf9 [
].Yeast inositol regulator SCS2, a VAP33 homologue. It is C-terminally anchored to the endoplasmic reticulum [
].The MSP polypeptide chain has an immunoglobulin-like fold based on a seven-stranded beta sandwich measuring approximately 15 A x 20 A x 45 A and having opposing three-stranded and four-stranded beta sheets [].This entry represents the MSP domain.
Transcriptional induction of the uspA gene of Escherichia coli occurs
when conditions cause growth arrest; cells deficient in UspA survivepoorly in stationary phase [
]. The product of uspA has been shown to bea cytoplasmic serine and threonine phosphoprotein. Members of the Usp
family are predicted to be related to the MADS-box proteins and bind to DNA[
]. Some members of the family contain 2 copies of the domain. The structure of a UspA homologue from Methanocaldococcus jannaschii (Methanococcus jannaschii) from has
been determined to 1.8 angstroms resolution by using its selenomethionyl derivativeand multiwavelength anomalous diffraction. The protein homodimerises in
the crystal; each monomer adopts an open-twisted 5-stranded parallel β-sheet with 2 helices on each side of the sheet []. Although the structureco-crystallised with ATP, the function of the protein is unknown.
This entry includes five E. coli Usp paralogues: uspA, uspC, uspD, uspF and uspG [
].
Thioredoxin domain-containing protein 17-like domain
Type:
Domain
Description:
This domain can be found in thioredoxin domain-containing protein 17 (also known as TRP14), which is a highly conserved and ubiquitously expressed oxidoreductase involved in controlling of cellular redox signalling pathways. TXNDC17 has been shown to efficiently reduce l-cystine and can directly reactivate oxidized protein-tyrosine phosphatase PTP1B [
].
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 family consists of ribosomal protein L5 from eukaryotes. The ribosomal 5S RNA is the only known rRNA species to bind a ribosomal protein before its assembly into the ribosomal subunits [
]. In eukaryotes, the 5S rRNA molecule binds one protein species, a 34kDa protein which has been implicated in the intracellular transport of 5 S rRNA [
]. This family also includes ribosomal proteins L18 from archaea.
The members of this family include sequences that are parts of hypothetical proteins expressed by plant species. The region in question is about 170 amino acids long.
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 L23 is one of the proteins from the large ribosomal subunit that binds to a specific region on either the 23S or 26S rRNA. This entry includes eukaryotic L25 and bacterial and eukaryotic L23.
Proteins containing this domain include an accessory subunit of the higher eukaryotic NADH dehydrogenase complex. In Saccharomyces cerevisiae, the Isd11 protein (
) has been shown to play a role in Fe/S cluster biogenesis in mitochondria [
,
]. We have named this family LYR after a highly conserved tripeptide motif close to the N terminus of these proteins.
Translocon-associated protein (TRAP), alpha subunit
Type:
Family
Description:
The alpha-subunit of the TRAP (translocon-associated protein, also known as signal sequence receptor 1/alpha subunit, SSRA) complex is a single-spanning membrane protein of the endoplasmic reticulum (ER) [
,
]. The four-subunit (alpha, beta, gamma and delta) TRAP complex localises in the ER membrane and associates with the Sec61 translocon as a heterotetramer []. It also interacts with palmitoylated calnexin (CALX), the interaction is required for efficient folding of glycosylated proteins []. TRAP complex may also be involved in endoplasmic reticulum-associated degradation []. TRAP-alpha plays a critical role in the biosynthesis of insulin, being involved in preproinsulin translocation and proinsulin trafficking which may contribute to the pathogenesis of type 2 diabetes [].
The FtsZ family of proteins are involved in polymer formation. FtsZ is the polymer-forming protein of bacterial cell division. It is part of a ring in the middle of the dividing cell that is required for constriction of cell membrane and cell envelope to yield two daughter cells. FtsZ is a GTPase, like tubulin [
]. FtsZ can polymerise into tubes, sheets, and rings in vitro and is ubiquitous in eubacteria and archaea [].This entry represents a domain of FtsZ. In most FtsZ proteins is found in the C terminus, except in some alphaproteobacteria proteins where there is an extension C-terminal domain
.
CDK5RAP3 (also known as C53 or LZAP) serves as a probable tumour suppressor initially identified as a CDK5R1 interactor controlling cell proliferation [
,
]. It negatively regulates NF-kappa-B-mediated gene transcription through the control of RELA phosphorylation [,
]. It also regulates mitotic G2/M transition checkpoint and mitotic G2 DNA damage checkpoint [,
]. It has been shown to bind Wip1 and stimulates its phosphatase activity [].
Proteins resident in the lumen of the endoplasmic reticulum (ER) contain a C-terminal
tetrapeptide, commonly known as Lys-Asp-Glu-Leu (KDEL) in mammals and His-Asp-Glu-Leu(HDEL) in yeast (Saccharomyces cerevisiae) that acts as a signal for their retrieval from subsequent
compartments of the secretory pathway. The receptor for this signal is a ~26kDa Golgimembrane protein, initially identified as the ERD2 gene product in S. cerevisiae. The
receptor molecule, known variously as the ER lumen protein retaining receptor or the'KDEL receptor', is believed to cycle between the cis side of the Golgi apparatus andthe ER. It has also been characterised in a number of other species, including plants,
Plasmodium, Drosophila and mammals. In mammals, 2 highly related forms of thereceptor are known. The KDEL receptor is a highly hydrophobic protein of 220 residues; its sequence
exhibits 7 hydrophobic regions, all of which have been suggested to traverse themembrane [
]. More recently, however, it has been suggested that only 6 of theseregions are transmembrane (TM), resulting in both N- and C-termini on the cytoplasmic
side of the membrane.
This domain is found at the C terminus of the ribosome biogenesis protein BMS1 and TSR1 families, which may act as a molecular switch during maturation of the 40S ribosomal subunit in the nucleolus.
Ctf8 is a component of the RFC-like complex CTF18-RFC which is required for efficient establishment of chromosome cohesion during S-phase and may load or unload POL30/PCNA. During a clamp loading circle, the RFC:clamp complex binds to DNA and the recognition of the double-stranded/single-stranded junction stimulates ATP hydrolysis by RFC [,
].
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 archaebacterial ribosomal proteins can be grouped in this family of ribosomal proteins, S17e (RPS17e). They include, vertebrate, Drosophila and Neurospora crassa (crp-3) S17's as well as yeast S17a (RP51A) and S17b (RP51B) and archaebacterial S17e [
,
,
].
Membrane-associated, eicosanoid/glutathione metabolism (MAPEG) protein
Type:
Family
Description:
This entry represents a widespread protein family known as MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism) [
]. This group of membrane associated proteins with highly divergent functions, such as the metabolism of eicosanoids [,
]. Included are:5-lipoxygenase activating protein (gene FLAP), which seems to be required for the activation of 5-lipoxygenase.Leukotriene C4 synthase (
), which catalyses the production of LTC4 from LTA4. The structure of human LTC4S was solved by X-ray crystallography [
]. Microsomal glutathione S-transferase II (
) (GST-II), which also produces LTC4 from LTA4. These enzymes play an important role in the resistance to temperature stresses and lipid peroxidation [
,
]. Prostaglandin E synthase, which catalyses the synthesis of PGE2 from PGH2 (produced by cyclooxygenase from arachidonic acid). Because of structural similarities in the active sites of FLAP, LTC4 synthase and PGE synthase, substrates for each enzyme can compete with one another and modulate synthetic activity.
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 conserved site in the ribosomal protein L19 from eukaryotes, as well as in L19e from archaea [
]. L19/L19e is absent in bacteria. L19/L19e is part of the large ribosomal subunit.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].Ribosomal protein L19 from eukaryotes and L19e from archaea [
] form part of the large ribosomal subunit, whose structure has been determined in a number of eukaryotic and archaeal species []. L19/L19e is a multi-helical protein consisting of two different 3-helical domains connected by a long, partly helical linker. This superfamily represents an α-helical domain that assumes an orthogonal bundle topology from ribosomal protein L19e from archaea.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].This entry represents the ribosomal protein L19 from eukaryotes, as well as L19e from archaea [
]. L19/L19e is absent in bacteria. L19/L19e is part of the large ribosomal subunit, whose structure has been determined in a number of eukaryotic and archaeal species []. L19/L19e is a multi-helical protein consisting of two different 3-helical domains connected by a long, partly helical linker. This superfamily represents an α-helical domain that assumes an orthogonal bundle topology.
All proteins in this family for which functions are known are components of a multiprotein complex used for targeting nucleotide excision repair to specific parts of the genome. Rad23 contains a ubiquitin-like domain that interacts with catalytically active proteasomes and two ubiquitin
(Ub)-associated (UBA) sequences that bind Ub. Rad23 interacts with ubiquitinated cellular proteins through thesynergistic action of its UBA domains. In
humans, Rad23 complexes with the XPC protein.
Members of this eukaryotic family are part of the group II chaperonin complex called CCT (chaperonin containing TCP-1 or Tailless Complex Polypeptide 1) or TRiC [
,
]. Chaperonins are involved in productive folding of proteins []. They share a common general morphology, a double toroid of 2 stacked rings. The archaeal equivalent group II chaperonin is often called the thermosome []. Both the thermosome and the TCP-1 family of proteins are weakly, but significantly [], related to the cpn60/groEL chaperonin family (see ).
The TCP-1 protein was first identified in mice where it is especially abundant in testis but present in all cell types. It has since been found and characterised in many other animal species, as well as in yeast, plants and protists. The TCP1 complex has a double-ring structure with central cavities where protein folding takes place [
]. TCP-1 is a highly conserved protein of about 60kDa (556 to 560 residues) which participates in a hetero-oligomeric 900kDa double-torus shaped particle [] with 6 to 8 other different, but homologous, subunits []. These subunits, the chaperonin containing TCP-1 (CCT) subunit beta, gamma, delta, epsilon, zeta and eta are evolutionary related to TCP-1 itself [,
]. Non-native proteins are sequestered inside the central cavity and folding is promoted by using energy derived from ATP hydrolysis [
,
,
]. The CCT is known to act as a molecular chaperone for tubulin, actin and probably some other proteins [,
].This family consists exclusively of the CCT zeta chain (part of a paralogous family) from animals, plants, fungi, and other eukaryotes.
This entry represents the HMGA family, whose members contain DNA-binding domains, also known as AT hooks due to their ability to interact with the narrow minor groove of AT-rich DNA sequences. They play an important role in chromatin organisation [
].The high mobility group (HMG) proteins are the most abundant and ubiquitous nonhistone chromosomal proteins. They bind to DNA and to nucleosomes and are involved in the regulation of DNA-dependent processes such as transcription, replication, recombination, and DNA repair. They can be grouped into three families: HMGB (HMG 1/2), HMGN (HMG 14/17) and HMGA (HMG I/Y). The characteristic domains are: AT-hook for the HMGA family, the HMG Box for the HMGB family, and the nucleosome-binding domain (NBD) for the members of the HMGN family [
].
This family consists of several small bacterial proteins several of which are classified as putative lipoproteins. The function of this family is unknown.
The ATP-Binding Cassette (ABC) superfamily forms one of the largest of all protein families with a diversity of physiological functions [
]. Several studies have shown that there is a correlation between the functional characterisation and the phylogenetic classification of the ABC cassette [,
]. More than 50 subfamilies have been described based on a phylogenetic and functional classification [,
,
]; (for further information see http://www.tcdb.org/tcdb/index.php?tc=3.A.1).The vitamin B12-binding protein BtuF is part of the ABC transporter complex BtuCDF involved in vitamin B12 import. This protein binds vitamin B12 and delivers it to the periplasmic surface of BtuC [
].
Secretion across the inner membrane in some Gram-negative bacteria occurs via the preprotein translocase pathway. Proteins are produced in the cytoplasm as precursors, and require a chaperone subunit to direct them to the translocase component [
]. From there, the mature proteins are either targeted to the outer membrane, or remain as periplasmic proteins. The translocase protein subunits are encoded on the bacterial chromosome.The translocase itself comprises 7 proteins, including a chaperone protein (SecB), an ATPase (SecA), an integral membrane complex (SecCY, SecE and SecG), and two additional membrane proteins that promote the release of the mature peptide into the periplasm (SecD and SecF) [
]. The chaperone protein SecB [] is a highly acidic homotetrameric protein that exists as a "dimer of dimers"in the bacterial cytoplasm. SecB maintains preproteins in an unfolded state after translation, and targets these to the peripheral membrane protein ATPase SecA for secretion [
].The tertiary structure of Haemophilus influenzae SecB (
) was resolved by means of X-ray crystallography to 2.5A [
]. The chaperone comprises four chains, forming a tetramer, each chain of which has a simple alpha+beta fold arrangement. While one binding site on the homotetramer recognises unfolded polypeptides by hydrophobic interactions, the second binds to SecA through the latter's C-terminal 22 residues.
The BcsQ (also known as YhjQ) protein is encoded immediately upstream of bacterial cellulose synthase (bcs) genes in a broad range of bacteria, including both copies of the bcs locus in Klebsiella pneumoniae, and in several species is clearly part of the bcs operon. It is identified as a probable component of the bacterial cellulose metabolic process not only by gene location, but also by partial phylogenetic profiling, or Haft-Selengut algorithm [
], based on a bacterial cellulose biosynthesis genome property profile.Cellulose plays an important role in biofilm formation and structural integrity in some bacteria. E. coli csQ may play a role in subcellular localization of an active cellulose biosynthesis apparatus at the bacterial cell pole [
].
Ribosomal protein L33 is one of the proteins from the large ribosomal subunit. In Escherichia coli, L33 has been shown to be on the surface of 50S subunit. L33 belongs to a family of ribosomal proteins which, on the basis of sequence similarities [
,
], groups:Eubacterial L33.Algal and plant chloroplast L33.Cyanelle L33.L33 is a small protein of 49 to 66 amino-acid residues.
D-xylose ABC transporter, substrate-binding protein
Type:
Family
Description:
This entry represents the D-xylose ABC transporter substrate-binding protein which is a periplasmic (when in Gram-negative bacteria) binding protein for D-xylose import by a high-affinity ATP-binding cassette (ABC) transporter [
,
,
].Bacterial high affinity transport systems are involved in active transport of solutes across the cytoplasmic membrane. Most of the bacterial ABC (ATP-binding cassette) importers are composed of one or two transmembrane permease proteins, one or two nucleotide-binding proteins and a highly specific periplasmic solute-binding protein. In Gram-negative bacteria the solute-binding proteins are dissolved in the periplasm, while in archaea and Gram-positive bacteria, their solute-binding proteins are membrane-anchored lipoproteins [
,
].
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 L31 is one of the proteins from the large ribosomal subunit. L31 is a protein of 66 to 97 amino-acid residues which has only been found so far in bacteria and in some plant and algal chloroplasts.This entry represents 50S ribosomal protein L31 from the type B subfamily.
This entry represents several hypothetical bacterial proteins of around 50 residues in length. The function of this family is unknown but is thought to be a membrane protein.
Bacterial high affinity transport systems are involved in active transport of solutes across the cytoplasmic membrane. Most of the bacterial ABC (ATP-binding cassette) importers are composed of one or two transmembrane permease proteins, one or two nucleotide-binding proteins and a highly specific periplasmic solute-binding protein. In Gram-negative bacteria the solute-binding proteins are dissolved in the periplasm, while in archaea and Gram-positive bacteria, their solute-binding proteins are membrane-anchored lipoproteins [,
,
].On the basis of sequence similarities, the vast majority of these solute-binding proteins can be grouped [
] into eight families or clusters, which generally correlate with the nature of the solute bound. This entry represents a domain found in the solute-binding protein family 5. Family 5 members include:Periplasmic oligopeptide-binding proteins (oppA) of Gram-negative bacteria and homologous lipoproteins in Gram-positive bacteria (oppA, amiA or appA)Periplasmic dipeptide-binding proteins of Escherichia coli (dppA) and Bacillus subtilis (dppE)Periplasmic murein peptide-binding protein of E. coli (mppA) Periplasmic peptide-binding proteins sapA of E. coli, Salmonella typhimurium and Haemophilus influenzaePeriplasmic nickel-binding protein (nikA) of E. coliHaem-binding lipoprotein (hbpA or dppA) from H. influenzaeLipoprotein xP55 from Streptomyces lividansHypothetical proteins from H. influenzae (HI0213) and Rhizobium sp. (strain NGR234) symbiotic plasmid (y4tO and y4wM)HTH-type transcriptional regulator SgrR from E. coli. The solute-binding domain is localised in its C-terminal [
].
This family consists of several hypothetical bacterial proteins of around 155 residues in length. Family members are present in Rhizobium, Agrobacterium and Streptomyces species.
This family of proteins is functionally uncharacterised. This protein is found in bacteria and viruses. Proteins in this family are typically between 144 to 163 amino acids in length. This protein has a conserved TPRF sequence motif.
This conserved hypothetical protein family with four predicted transmembrane regions is found in
Escherichia coli, Haemophilus influenzae, and Helicobacter pylori 26695, among completed genomes.This entry represents a group of uncharacterised proteins.
The OsmC-like proteins (
) contain several deeply split clades of homologous proteins. This clade includes the protein Ohr, or organic hydroperoxide resistance protein.
The HisI and HisE functions, phosphoribosyl-AMP cyclohydrolase
and phosphoribosyl-ATP pyrophosphatase
, are coded by a a single gene in E. coli and other bacteria [
]. This entry represents bifunctional HisIE proteins. This entry also includes its plant homologues, such as HISN2 (At1g31860) from Arabidopsis [].
Family member Shigella flexneri VirK (
) is a virulence protein required for the expression, or correct membrane localisation of IcsA (VirG) on the bacterial cell surface [
,
]. This family also includes Pasteurella haemolytica lapB (), which is thought to be membrane-associated.
Escherichia coli protein Dps [
] is a DNA-binding protein, synthesized during prolonged starvation, that seems to protect DNA from oxidative damage. Dps binds DNA without any apparent sequence specificity. It is a protein of about 19 Kd that associates into a complex of 12 subunits forming two stacked hexameric rings.Proteins similar to Dps have been found in other bacteria:Bacillus subtilis protein MrgA.Antigen TpF1/TyF1 from Treponema pallidum.Haemophilus ducreyi fine tangled pili major subunit (gene ftpA).Helicobacter pylori neutrophil-activating protein A (gene napA).Listeria innocua non-heme iron-containing ferritin.Synechococcus elongatus (strain PCC 7942) (Anacystis nidulans R2) nutrient-stress induced DNA binding protein (gene dpsA).A low-temperature induced protein from Anabaena variabilis.Haemophilus influenzae hypothetical protein HI1349.Synechocystis sp. (strain PCC 6803) hypothetical protein Slr1894.A hypothetical protein encoded in the 5' region of a gene coding for a bromoperoxidase, in plasmid pOP2621 of Streptomyces aureofaciens.All these proteins share a conserved region of about 50 residues in their central region. This entry corresponds to two conserved sites derived from both extremities of that region.
This is entry represents the probable transcriptional regulatory protein YeeN family. In Pseudomonas aeruginosa, a member of this family, PmpR, is involved in regulation of the quinolone signal (PQS) system and of pyocyanine production. It negatively regulates the quorum-sensing response regulator pqsR of the PQS system by binding to its promoter region [
].
Energy-dependent translational throttle protein EttA
Type:
Family
Description:
ABC-F proteins compose one of the most widely distributed branches of the ATP-binding cassette (ABC) superfamily. EttA/YjjK is the most prevalent eubacterial ABC-F protein. Its role consists in gating ribosome entry into the translation elongation cycle through a nucleotide-dependent interaction sensitive to ATP/ADP ratio [
]. The ATP-bound form of EttA binds to the ribosomal tRNA-exit site, and forms a bridge between the ribosomal L1 stalk and the tRNA bound in the peptidyl-tRNA-binding site []. EttA may regulate protein synthesis in energy-depleted cells, which have a low ATP/ADP ratio.
This entry includes the Inner membrane protein YbjO which appears to be restricted to Enterobacteriaceae. From AlphaFold structure predictions, it has been suggested that these proteins may function as dehydrogenases, accounting in its structural similarity with the C-terminal region of Acyl-CoA dehydrogenases.
This family consists of several hypothetical bacterial proteins but contains one sequence Ree1 (
) from Saccharomyces cerevisiae [
]. Members of this family are typically around 200 residues in length. The function of this family is unknown.
This entry represents the C-terminal domain of the H-NS DNA binding protein. It is composed of an antiparallel β-sheet, an α-helix and a 3 (10)-helix which form a hydrophobic core, stabilising the whole structure. This domain has been found to bind to DNA [
].
This family consists of a number of sequences which are highly similar to the Tir chaperone protein in Escherichia coli. In many Gram-negative bacteria, a key indicator of pathogenic potential is the possession of a specialised type III secretion system, which is utilised to deliver virulence effector proteins directly into the host cell cytosol. Many of the proteins secreted from such systems require small cytosolic chaperones to maintain the secreted substrates in a secretion-competent state. CesT serves a chaperone function for the enteropathogenic Escherichia coli (EPEC) translocated intimin receptor (Tir) protein, which confers upon EPEC the ability to alter host cell morphology following intimate bacterial attachment [
]. This family also contains the chaperone protein sicP [
] and several DspF and related sequences from several plant pathogenic bacteria. The "disease-specific"(dsp) region next to the hrp gene cluster of Erwinia amylovora is required for pathogenicity but not for elicitation of the hypersensitive reaction. DspF and AvrF are small (16kDa and 14kDa) and acidic with predicted amphipathic alpha helices in their C termini; they resemble chaperones for virulence factors secreted by type III secretion systems of animal pathogens [
].This entry also includes Pseudomonas aeruginosa ExsC, which functions as a chaperone for ExsE. It is also part of the regulatory cascade that plays a role in the transcriptional regulation of the type III secretion system (T3SS) [
]. The family also contains a number of proteins from eukaryotic parasites.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].Evidence suggests that, in prokaryotes, the peptidyl transferase reaction is performed by the large subunit 23S rRNA, whereas proteins probably have a greater role in eukaryotic ribosomes. Most of the proteins lie close to, or on the surface of, the 30S subunit, arranged peripherally around the rRNA [
]. The small subunit ribosomal proteins can be categorised as primary binding proteins, which bind directly and independently to 16S rRNA; secondary binding proteins, which display no specific affinity for 16S rRNA, but its assembly is contingent upon the presence of one or more primary binding proteins; and tertiary binding proteins, which require the presence of one or more secondary binding proteins and sometimes other tertiary binding proteins.The small ribosomal subunit protein S18 is known to be involved in binding the aminoacyl-tRNA complex in Escherichia coli [
], and appears to be situated at the tRNA A-site. Experimental evidence has revealed that S18 is well exposed on the surface of the E. coli ribosome, and is a secondary rRNA binding protein []. S18 belongs to a family of ribosomal proteins [] that includes: eubacterial S18; metazoan mitochondrial S18, algal and plant chloroplast S18; and cyanelle S18.
This entry represents the central domain of bacterial DnaA proteins [
,
,
] which play an important role in initiating and regulating chromosomal replication. DnaA is an ATP- and DNA-binding protein. It binds specifically to 9 bp nucleotide repeats known as dnaA boxes which are found in the chromosome origin of replication (oriC).DnaA is a protein of about 50kDa that contains two conserved regions: the first is located in the N-terminal half and corresponds to the ATP-binding domain, the second is located in the C-terminal half and could be involved in DNA-binding. The protein may also bind the RNA polymerase beta subunit, the dnaB and dnaZ proteins, and the groE gene products (chaperonins) [].
This entry represents bacterial members of the uncharacterised protein family UPF0761. It includes the E. coli gene product of yihY, and was previously thought to be a family of tRNA-processing ribonuclease BN proteins [
]. This has been shown to be incorrect [].
Periplasmic protein thiol:disulphide oxidoreductase DsbE
Type:
Family
Description:
Periplasmic protein thiol:disulphide oxidoreductase is involved in the biogenesis of c-type cytochromes [
] as well as in disulphide bond formation in some periplasmic proteins. This group defines the DsbE (also known as CcmG and CycY) subfamily. DsbE is a membrane-anchored, periplasmic TRX-like reductase containing a CXXC motif [] that specifically donates reducing equivalents to apocytochrome c via CcmH, another cytochrome c maturation (Ccm) factor with a redox active CXXC motif []. Assembly of cytochrome c requires the ligation of heme to reduced thiols of the apocytochrome. In bacteria, this assembly occurs in the periplasm. The reductase activity of DsbE in the oxidizing environment of the periplasm is crucial in the maturation of cytochrome c [,
].
MreB proteins are essential for cell-shape maintenance and cell morphogenesis in most non-spherical bacteria [
,
]. Most rod-shaped or non-spherical bacteria possess at least one mreB homologue. In Bacillus subtilis, sidewall elongation during vegetative growth is controlled by three MreB isoforms: MreB, Mbl and MreBH []. MreB proteins are found in rod-shaped bacteria, such as E. coli and B. subtilis, that grow by dispersed intercalation of new wall material along the long axis of the cell, as opposed to those that grow from the cell pole [].The crystal structure of MreB from Thermotoga maritima was resolved using X-ray crystallography, and the results suggested that MreB proteins form long filaments that wrap around the long axis of the cell close to the cell membrane, forming helix-like structures. These observations led to the idea that MreB proteins might have an actin-like cytoskeletal role in bacteria [
,
]. However, this remains controversial [,
]. MreB and MreB-like proteins are thought to act as scaffolds, guiding the localization and activity of key peptidoglycan synthesizing proteins during cell elongation [
, ]. MreB has also been implicated in chromosome segregation [].
Toluene tolerance Ttg2/phospholipid-binding protein MlaC
Type:
Family
Description:
This family includes toluene tolerance protein Ttg2 and intermembrane phospholipid transport system binding protein MlaC. Proteins in this family show similarity to ABC transporters [
,
].Toluene tolerance is mediated by increased cell membrane rigidity resulting from changes in fatty acid and phospholipid compositions, exclusion of toluene from the cell membrane, and removal of intracellular toluene by degradation [
]. Ttg2 is one of the many proteins involved in these processes [].MlaC actively prevents phospholipid accumulation at the cell surface. It probably maintains lipid asymmetry in the outer membrane by retrograde trafficking of phospholipids from the outer membrane to the inner membrane. It may transfer phospholipid across the periplasmic space and deliver it to the mlaFEDB complex at the inner membrane [
].
The function of this family is unknown. Aquifex aeolicus has two copies of this protein. A probable aspartyl-tRNA synthetase from Escherichia coli [
] belongs to this group.
This superfamily represents the C-terminal alpha/beta domain from the heat shock protein Hsp33. Hsp33 is a molecular chaperone, distinguished from all other known chaperones by its mode of functional regulation. Its activity is redox regulated. Hsp33 is a cytoplasmically localised protein with highly reactive cysteines that respond quickly to changes in the redox environment. Oxidizing conditions like H
2O
2cause disulphide bonds to form in Hsp33, a process that leads to the activation of its chaperone function [
].
This superfamily represents the N-terminal, 3-layer beta/alpha/beta domain from the heat shock protein Hsp33. Hsp33 is a molecular chaperone, distinguished from all other known chaperones by its mode of functional regulation. Its activity is redox regulated. Hsp33 is a cytoplasmically localised protein with highly reactive cysteines that respond quickly to changes in the redox environment. Oxidizing conditions like H
2O
2cause disulphide bonds to form in Hsp33, a process that leads to the activation of its chaperone function [
].
Geminiviruses are characterised by a genome of circular single-stranded DNA encapsidated in twinned (geminate) quasi-isometric particles, from which the group derives its name [
]. Most geminiviruses can be divided into two subgroups on the basis of host range and/or insect vector: i.e. those that infect dicotyledenous plants and are transmitted by the same whitefly species, and those that infect monocotyledenous plants and are transmitted by different leafhopper vectors. The genomes of the whitefly-transmitted African cassava mosaic virus, Tomato golden mosaic virus (TGMV) and Bean golden mosaic virus (BGMV) possess a bipartite genome. By contrast, only a single DNA component has been identified for the leafhopper-transmitted Maize streak virus (MSV) and Wheat dwarf virus (WDV) [,
]. Beet curly top virus (BCTV), and Tobacco yellow dwarf virus belong to a third possible subgroup. Like MSV and WDV, BCTV is transmitted by a specific leafhopper species, yet like the whitefly-transmitted geminiviruses it has a host range confined to dicotyledenous plants.Sequence comparison of the whitefly-transmitted Squash leaf curl virus (SqLCV) and Tomato yellow leaf curl virus (TYLCV) with the genomic components of TGMV and BGMV reveals a close evolutionary relationship [
,
,
]. Amino acid sequence alignments of Potato yellow mosaic virus (PYMV) proteins with those encoded by other geminiviruses show that PYMV is closely related to geminiviruses isolated from the New World, especially in the putative coat protein gene regions []. Comparison of MSV DNA-encoded proteins with those of other geminiviruses infecting monocotyledonous plants, including Panicum streak virus [] and Miscanthus streak virus (MiSV) [], reveal high levels of similarity.
This family consists of several hypothetical bacterial proteins of around 340 residues in length. Members of this family contain six highly conserved cysteine residues. The function of this family is unknown.
