Proteins in this entry are homologues of YicC (
) from Escherichia coli. Although it is relatively poorly characterised YicC has been shown to be important for cells in the stationary phase, and essential for growth at high temperatures [
].
This entry represents the N-terminal domain of the ModE protein. ModE is a molybdate-activated repressor of the molybdate transport operon in E. coli. It consists of the N-terminal domain represented by this entry and two tandem copies of mop-like domain, where Mop proteins are a family of 68-residue molybdenum-pterin binding proteins of Clostridium pasteurianum. Proteins containing this domain also includes a few archaeal proteins that lack Mop-like domains. PSI-BLAST analysis shows similarity to helix-turn-helix regulatory proteins [
].Molybdenum-dependent repression of transcription of the Escherichia coli modABCD
operon, which encodes the high-affinity molybdate transporter, is mediated by the ModE protein. When molybdate or tungstate bind to ModE there is little change in its α-helical content, but a major change in the environment of tryptophan and tyrosine residues occurs [
]. This is the N-terminal domain of molybdenum-binding proteins ModE, ModA, MopA and MopB. These proteins
are involved in molybdenum transport. ModE acts both as a repressor and activator of the mod and moa operons, respectively, depending on the properties of the binding site [].
This entry represents a famiy of bifunctional serine/threonine kinase/phosphorylases involved in the regulation of the phosphoenolpyruvate synthase (PEPS) by catalysing its phosphorylation/dephosphorylation [
].
The OEP family (Outer membrane efflux protein) form trimeric channels that allow export of a variety of substrates in Gram-negative bacteria. Each member of this family is composed of two repeats. The trimeric channel is composed of a 12
stranded all beta sheet barrel that spans the outer membrane, and a long all helical barrel that spans the periplasm. Examples include the Escherichia coli TolC outer membrane protein, which is required for proper expression of outer membrane protein genes; the Rhizobium nodulation protein; and the Pseudomonas FusA protein, which is involved in resistance to fusaric acid.
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.
HflK is a bacterial membrane protein which is thought, together with the HflC protein, to form a membrane protease complex whose activity is modulated by the GTPase HflX [
]. This entry represents the N-terminal, membrane-spanning, region of of HflK responsible for anchoring the protein in the bacterial membrane. It is often found in association with .
Within the bacterial flagellum, the basal-body rod, the hook, the hook-
associated proteins (HAPs), and the helical filament together constitute an axial substructure whose elements share structural features and a common
export pathway []. This entry represents the hook-associated protein 1 (HAP1, also known as FlgK) []. The structure of FlgK from Burkholderia pseudomallei has been revealed []. The amino acid sequences of the hook protein and of the
three hook-associated proteins of Salmonella typhimurium have been deduced from the DNA sequences of their structural genes (flgE, flgK, flgL and fliD respectively).
These sequences have been compared with each other and with those for the filament protein (flagellin) and four rod proteins. The hook protein
was found to be most similar to the distal rod protein (FlgG) and theproximal hook-associated protein (HAP1), which are thought to be attached to the proximal and
distal ends of the hook, the similarities being most pronounced near the N-and C-termini.
It is thought that the axial proteins may adopt amphipathic α-helicalconformations at their N- and C-termini. These regions of the filament and
hook are believed to be responsible for quaternary interactions betweensubunits. Interaction between N- and C-terminal α-helices may be
important in the formation of the axial structures of the flagellum.Although consensus sequences have been noted, no consensus extends to the
entire set of axial proteins. Thus the basis for recognition of a proteinfor export by the flagellum-specific pathway remains to be identified.
RcnB is a family of Proteobacteria proteins. RcnB is required for maintaining metal ion homeostasis, in conjunction with the efflux pump RcnA, family NicO [
,
,
].
This family of short proteins includes DNA-damage-inducible protein I (DinI) and related proteins. The SOS response, a set of cellular phenomena exhibited by eubacteria, is initiated by various causes that include DNA damage-induced replication arrest, and is positively regulated by the co- protease activity of RecA. Escherichia coli DinI, a LexA-regulated SOS gene product, shuts off the initiation of the SOS response when overexpressed
in vivo. Biochemical and genetic studies indicated that DinI physically interacts with RecA to inhibit its co-protease activity [
]. The structure of DinI is known [].
The protein represented by this entry, YggX, serves to protect Fe-S clusters from oxidative damage []. The effect is two-fold: proteins that rely on Fe-S clusters do not become inactivated, and the release of free iron and hydrogen peroxide--a DNA damaging agent--is prevented. These observations are consistent with the hypothesis that YggX chelates free iron, and recent experiments show that YggX can indeed bind Fe(II) in vitro and in vivo []. Furthermore, YggX has a positive effect on the action of at least one Fe(II)-responsive protein. The combined actions of YggX is reminiscent of iron trafficking proteins [], and YggX is therefore proposed to play a role in Fe(II) trafficking []. In Escherichia coli, YggX was shown to be under the transcriptional control of the redox-sensing SoxRS system [].
GpW is a 68 residue protein known to be present in phage particles. Extracts of phage-infected cells lacking GpW contain DNA-filled heads, and active tails, but no infectious virions. GpW is required for the addition of GpFII to the head, which is, in turn, required for the attachment of tails. Since GpFII and tails are known to be attached at the connector, GpW is also likely to assemble at this site. The addition of GpW to filled heads increases the DNase resistance of the packaged DNA, suggesting that GpW either forms a plug at the connector to prevent ejection of the DNA, or binds directly to the DNA. The large number of positively charged residues in GpW (its calculated pI is 10.8) is consistent with a role in DNA interaction [
].
This family consists of several bacterial phage shock protein B (PspB) sequences. The phage shock protein (psp) operon is induced in response to heat, ethanol, osmotic shock and infection by filamentous bacteriophages [
]. Expression of the operon requires the alternative sigma factor sigma54 and the transcriptional activator PspF. In addition, PspA plays a negative regulatory role, and the integral-membrane proteins PspB and PspC play a positive one [].
Bacteriophage lambda head decoration protein D stabilises the head shell after the rearrangement of GP7 subunits of the head shell lattice that accompanies expansion of the head. There are approximately 420 copies of protein D per mature phage.
This superfamily represents N-terminal domain of histone-like H-NS proteins that is responsible for dimerisation and involved in transcriptional repression [
,
,
,
,
].
This domain is found in the Haemophilus influenzae opacity-associated protein (OapA). It is required for efficient nasopharyngeal mucosal colonisation, and its expression is associated with a distinctive transparent colony phenotype. OapA is thought to be a secreted protein, and its expression exhibits high-frequency phase variation [
,
]. This motif occurs at the N terminus of these proteins. It contains a conserved histidine followed by a run of hydrophobic residues. Many of the proteins in this entry are unassigned peptidases belonging to MEROPS peptidase family M23B.
This family consists of several bacterial proteins and includes the Escherichia coli genes for ElaB, YgaM and YqjD.YqjD is an inner membrane and ribosome binding protein expressed during the stationary growth phase. It is possible that YqjD inactivates ribosomes by localizing a part of the ribosome to the membrane during the stationary phase [
]. Its expression is regulated by stress response sigma factor RpoS. The two paralogues of YqjD, ElaB and YgaM, are expressed and bind to ribosomes in a similar manner to YqjD [,
]. These proteins may have important cellular roles during the stress response. ElaB has been shown to protect cells against oxidative and heat shock stress [].
This domain is found in protein U, a spore coat protein produced at the late stage of development of Myxococcus xanthus. Protein U is produced as a secretory precursor, pro-protein U, which is then secreted across the membrane to assemble on the spore surface [
]. This domain is also found in a number of the genes within a conserved polycistronic operon that encodes a novel chaperone-usher pili assembly system. Examples are CsuA/B of Acinetobacter baumannii, and the CsuA, CsuB and CsuE of Vibrio parahaemolyticus and the related genes of Yersinia pestis.
In A. baumannii, csuC and csuE are required in the early steps of the process that that leads to biofilm formation. The conservation of the genes and gene order among unrelated bacteria, suggests that the csu operon is widespread and is involved in surface pilus formation which allows the bacteria to form biofilms on abiotic surfaces, a property that may aid there survival in their natural environment [
].
The bacteriophage P2 capsid is formed by multiple copies of the capsid protein GpN. The scaffolding protein GpO, which is essential for the assembly of this capsid, consists of an N-terminal serine protease domain and a C-terminal scaffolding domain [
,
]. During capsid assembly, GpO interacts with GpN via the N-terminal domain, while the C-terminal domain plays an essential role as a scaffold. When capsid assembly is complete the C-terminal domain of GpO is cleaved autocatalytically. Cleavage of GpN to its mature form by the remaining N-terminal domain then completes the maturation process.
YjbE is part of a four gene operon which is involved in exopolysaccharide production. The expression of YjbE is higher than the rest of the operon yjbEFGH. It appears to be restricted to Enterobacteriaceae [].
This family consists of several hypothetical bacterial proteins of around 70 residues in length. Members of this family are often referred to as YejL. The function of this family is unknown.
Virulence-related outer membrane proteins are expressed in Gram-negative bacteria and are essential to bacterial survival within macrophages and for eukaryotic cell invasion. Members of this group include: PagC, required by Salmonella typhimurium for survival in macrophages and for virulence in mice [
]
Rck outer membrane protein of the S. typhimurium virulence plasmid [
]
Ail, a product of the Yersinia enterocolitica chromosome capable of mediating bacterial adherence to and invasion of epithelial cell lines [
]
OmpX from Escherichia coli that promotes adhesion to and entry into mammalian cells. It also has a role in the resistance against attack by the human complement system [
]
a Bacteriophage lambda outer membrane protein, Lom []
The crystal structure of OmpX from E. coli reveals that OmpX consists of an eight-stranded antiparallel all-next-neighbour beta barrel [
]. The structure shows two girdles of aromatic amino acid residues and a ribbon of nonpolar residues that attach to the membrane interior. The core of the barrel consists of an extended hydrogen-bonding network of highly conserved residues. OmpX thus resembles an inverse micelle. The OmpX structure shows that the membrane-spanning part of the protein is much better conserved than the extracellular loops. Moreover, these loops form a protruding beta sheet, the edge of which presumably binds to external proteins. It is suggested that this type of binding promotes cell adhesion and invasion and helps defend against the complement system. Although OmpX has the same β-sheet topology as the structurally related outer membrane protein A (OmpA) , their barrels differ with respect to the shear numbers and internal hydrogen-bonding networks.
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 localized 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. In normal (reducing) cytosolic conditions, four conserved Cys residues are coordinated by a Zn ion. Hsp33 is homodimeric in its functional form [
,
,
,
].
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 2 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. It has been shown that the 104 N-terminal amino acids of the Maize streak virus coat protein bind DNA non-specifically [
].
The Trk system is a low to medium affinity potassium uptake system, widely found in both in bacteria and archaea, where the uptake of K(+) is believed to be linked to H(+) symport [
]. The core Trk system consists of two proteins, the integral membrane K(+)-translocating protein TrkH (or TrkG), and the regulatory NAD-binding peripheral membrane protein TrkA [,
,
]. In Escherichia coli the activity of TrkH is dependent on the ATP-binding protein SapD (also known as TrkE) which is part of the SapABCDF ABC transporter, involved in putrescine export []. Not all Trk systems are dependent on SapD however - it is thought that these may utilise ATP-binding proteins from other ABC transporters [].Sequence analysis of TrkA reveals that the protein consists of 2 tandemly arrayed halves that are 22% identical, a situation that might have arisen through gene duplication. TrkA also exhibits similarity to other Escherichia coli proteins [
], in particular KefC, a glutathione- regulated efflux protein [], and to various dehydrogenase proteins that possess NAD+binding sites. TrkA plays a regulatory role on TrkH gating. TrkA, binds ADP in its N2 domain to form a tetrameric ring which closes the channel. When ATP is bound to N1 and N2 domains of TrkA, it induces a tetramer-to-dimer conversion which opens TrkH [
].
This family includes intermembrane transport proteins PqiA and YebS, which are components of transport pathways that contribute to membrane integrity [
]. The promoter for the pqiA gene is inducible by paraquat, a superoxide radical-generating agent, and other known superoxide generators [].
This group of proteins are membrane bound transport proteins essential for ferric ion uptake in bacteria [
]. The family consists of ExbD, and TolR which are involved in TonB-dependent transport of various receptor bound substrates including colicins [].
This entry represents Der GTPase-activating protein YihI from Escherichia coli (strain K12) and similar proteins predominantly found in Gammaproteobacteria. YihI is a GTPase activating protein (GAP) that modifies the activity of Der, a 50S ribosomal subunit stability factor. The stimulation is specific to Der as YihI does not stimulate the GTPase activity of Era or ObgE. The interaction of YihI with Der requires only the C-terminal 78 amino acids of YihI [
]. A yihI deletion mutant is viable and shows a shorter lag period, but the same post-lag growth rate as a wild-type strain. yihI is expressed during the lag period. Overexpression of yihI inhibits cell growth and biogenesis of the 50S ribosomal subunit []. YihI is an unusual, highly hydrophilic protein with an uneven distribution of charged residues, resulting in an N-terminal region with high pI and a C-terminal region with low pI [].
Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP. There are several different types of transmembrane ATPases, which can differ in function (ATP hydrolysis and/or synthesis), structure (e.g., F-, V- and A-ATPases, which contain rotary motors) and in the type of ions they transport [
,
]. The different types include:F-ATPases (ATP synthases, F1F0-ATPases), which are found in mitochondria, chloroplasts and bacterial plasma membranes where they are the prime producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts).V-ATPases (V1V0-ATPases), which are primarily found in eukaryotes and they function as proton pumps that acidify intracellular compartments and, in some cases, transport protons across the plasma membrane [
]. They are also found in bacteria [].A-ATPases (A1A0-ATPases), which are found in Archaea and function like F-ATPases, though with respect to their structure and some inhibitor responses, A-ATPases are more closely related to the V-ATPases [,
].P-ATPases (E1E2-ATPases), which are found in bacteria and in eukaryotic plasma membranes and organelles, and function to transport a variety of different ions across membranes.E-ATPases, which are cell-surface enzymes that hydrolyse a range of NTPs, including extracellular ATP.F-ATPases (also known as ATP synthases, F1F0-ATPase, or H(+)-transporting two-sector ATPase) (
) are composed of two linked complexes: the F1 ATPase complex is the catalytic core and is composed of 5 subunits (alpha, beta, gamma, delta, epsilon), while the F0 ATPase complex is the membrane-embedded proton channel that is composed of at least 3 subunits (A-C), with additional subunits in mitochondria. Both the F1 and F0 complexes are rotary motors that are coupled back-to-back. In the F1 complex, the central gamma subunit forms the rotor inside the cylinder made of the alpha(3)beta(3) subunits, while in the F0 complex, the ring-shaped C subunits forms the rotor. The two rotors rotate in opposite directions, but the F0 rotor is usually stronger, using the force from the proton gradient to push the F1 rotor in reverse in order to drive ATP synthesis [
]. These ATPases can also work in reverse in bacteria, hydrolysing ATP to create a proton gradient.The atp operon of most prokaryotes contains the structural genes for the F-ATPase (ATP synthase), which are preceded by an atpI gene that encodes
a membrane protein of unknown function. AtpI is thought to support optimal ATP synthase assembly and stability [,
]. A role in magnesium uptake has also been suggested [].
This family summarizes bacterial proteins related to CpxP, a periplasmic protein that forms part of a two-component system which acts as a global modulator of cell-envelope stress in Gram-negative bacteria. CpxP aids in combating extracytoplasmic protein-mediated toxicity, and may also be involved in the response to alkaline pH [
]. Functioning as a dimer, it inhibits activation of the kinase CpxA, but also plays a vital role in the quality control system of P pili. It has been suggested that CpxP directly interacts with CpxA via its concave polar surface []. Another member of this family, Spy, is also a periplasmic protein that may be involved in the response to stress []. The homology between CpxP and Spy suggests similar functions. A characteristic 5-residue sequence motif LTXXQ is found repeated twice in many members of this family [].
FtsX is an integral membrane protein encoded in the same operon as signal recognition particle docking protein FtsY and FtsE. FtsE is a hydrophilic nucleotide-binding protein that associates with the inner membrane by means of association with FtsX; FtsE mutants are viable only in high salt, supporting possible roles in cell division, as previously indicated, or in transport [
]. FtsX is important for bacterial cell division, however its precise function is not yet known [,
]. FtsX is involved in sporulation in the Gram-positive bacterium Bacillus subtilis [].
This entry represents the thiol:disulphide interchange protein, DsbD (also known as DipZ). These proteins are thought to facilitate the correct formation of disufide bonds in some periplasmic proteins, as well as for the assembly of the periplasmic c-type cytochromes [
,
]. DsbD acts by transferring electrons from cytoplasmic thioredoxin to the periplasm. This transfer involves a cascade of disulfide bond formation and reduction steps [,
].
This family consists of several bacterial HicB related proteins. The function of HicB is unknown although it is thought to be involved in pilus formation. It has been speculated that HicB performs a function antagonistic to that of pili and yet is necessary for invasion of certain niches [
].
Bacterial Disulfide bond forming (Dsb) proteins facilitate proper folding and disulfide bond formation of periplasmic and secreted proteins [
].Thiol:disulphide interchange proteins DsbA and DsbL are involved in disulfide-bond formation [
,
]. They act by transferring its disulfide bond to other proteins and are reduced in the process. DsbA is required for disulfide bond formation in some periplasmic proteins such as PhoA or OmpA and is reoxidised by DsbB [,
]. DsbA is a monomeric thiol disulfide oxidoreductase protein containing a redox active CXXC motif imbedded in a TRX fold. It is involved in the oxidative protein folding pathway in prokaryotes, and is the strongest thiol oxidant known, due to the unusual stability of the thiolate anion form of the first cysteine in the CXXC motif []. The highly unstable oxidized form of DsbA directly donates disulfide bonds to reduced proteins secreted into the bacterial periplasm. This rapid and unidirectional process helps to catalyze the folding of newly-synthesized polypeptides. To regain catalytic activity, reduced DsbA is then reoxidized by the membrane protein DsbB, which generates its disulfides from oxidized quinones, which in turn are reoxidized by the electron transport chain []. DsbL is reoxidised by DsbI; DsbL and DsbI represent a second redox couple in some bacteria for specific substrates [].
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
This entry represents a structural domain found in the cell division protein ZapA, as well as in related proteins. This domain has a core structure consisting of two layers alpha/beta, and has a long C-terminal helix that forms dimeric parallel and tetrameric antiparallel coiled coils [
]. ZapA interacts with FtsZ, where FtsZ is part of a mid-cell cytokinetic structure termed the Z-ring that recruits a hierarchy of fission related proteins early in the bacterial cell cycle. ZapA drives the polymerisation and filament bundling of FtsZ, thereby contributing to the spatio-temporal tuning of the Z-ring.
This entry represents death-on-curing (Doc) proteins mostly from bacteria and archaea. Bacterial toxin-antitoxin (TA) system (or "addiction module") composed of closely linked genes encoding a stable toxin that can harm the host cell and its cognate labile antitoxin, which protects the host from the toxin's deleterious effect [
]. TA system plays a role in the adaptation of prokaryotes to stress conditions, the persistence phenomenon, programmed cell death and addiction to phages and mobile elements []. This entry includes Doc from bacteriophage P1, which forms a TA system with the prevents-host-death (Phd) protein [
,
]. It is a potent inhibitor of bacterial translation. It contains the Fido domain, also known as Fic domain, which contains a central motif conserved in most sequences (HPFx(D/E)GN(G/K)R), with the motif His contributing to Fic AMPylation (also known as adenylylation). However, Doc has been shown to be a protein kinase that inhibits bacterial translation by phosphorylating the conserved threonine (Thr-382) of the translation elongation factor EF-Tu rendering it unable to bind aminoacylated tRNAs [,
].
Within mitochondria and bacteria, a family of related proteins is involved in the assembly of periplasmic c-type cytochromes: these include CycK [
], CcmF [,
], NrfE [] and CcbS []. These proteins may play a role in guidance of apocytochromes and haem groups for their covalent linkage by the cytochrome-c-haem lyase. Members of the family are probably integral membrane proteins, with up to 16 predicted transmembrane (TM) helices.
This entry represents protein arginine N-methyltransferase PRMT7 [
].PRMT7 can catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA. It mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm D3 (SNRPD3); such methylation being required for the assembly and biogenesis of snRNP core particles. It also mediates the symmetric dimethylation of histone H4 'Arg-3' to form H4R3me2s. It plays a role in gene imprinting by being recruited by CTCFL at the H19 imprinted control region (ICR) and methylating histone H4 to form H4R3me2s, possibly leading to recruit DNA methyltransferases at these sites. It may also play a role in embryonic stem cell (ESC) pluripotency [
,
,
,
].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].The small ribosomal subunit protein S19 contains 88-144 amino acid residues.In Escherichia coli, S19 is known to form a complex with S13 that binds strongly to 16S ribosomal RNA. Experimental evidence [
] has revealed that S19 is moderately exposed on the ribosomal surface.
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 [
,
].Mitochondrial ribosomal protein L53 (also known as L44) is part of the 39S ribosome [
].
CRISPRs (clustered regularly interspaced short palindromic repeat) and CRISPR-associated (CAS) genes comprise an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements and conjugative plasmids). Although many different Cas protein families have been identified, the exact functions of most of their constituents are still unknown.This superfamily represents a C-terminal domain found in CAS proteins of the Csx1 family. The C-terminal domain of Csx1 proteins is greatly diversified, in contrast to the conserved N-terminal domain, which appears to play a common role in the homodimerisation of the protein [
].
This entry includes a group of WD repeat proteins, including DDB1- and CUL4-associated factor 11 (DCAF11) from animals and LEC14B from plants. DCAF11 may function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex [
]. The function of LEC14B from plants is not clear.
This entry models the short-form of the ribosomal L25 protein. The long-form has homology to the general stress protein Ctc of Bacillus subtilis, a mesophile, and ribosomal protein TL5 of Thermus thermophilus, a thermophile. Ribosomal protein L25 of Escherichia coli and Haemophilus influenzae appear to be orthologous but consist only of the N-terminal half of Ctc and TL5. Both short (L25-like) and full-length (CTC-like) members of this family bind the E-loop of bacterial 5S rRNA [
].
Lysosome membrane protein II (LIMP II) is a 478-residue glycoprotein
expressed in the membrane of lysosomes and secretory granules with lysosomalproperties [
]. The N-terminal segment (residues ~4-26) constitutes an uncleavable signal peptide [
]. LIMP II possesses an additional C-terminalhydrophobic region that, together with the signal peptide, may anchor the
protein to the membrane []. The major portion of the protein resides on theluminal side and contains 11 potential N-glycosylation sites and 5 cysteine
residues. The N- and C-terminal ends of the protein constitute short cytoplasmic tails. LIMP II is a subgroup of a larger family of the cell surface
protein CD36 involved in cell adhesion.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
GKAP1 is also called GKAP42. cGMP-dependent protein kinase (cGK) is a major cellular receptor of cGMP, playing important roles in cGMP-dependent signal transduction pathways [
]. Using the yeast two-hybrid system with cGK-Ialpha as a bait, a male germ- cell-specific 42kDa protein, GKAP42 (42kDa cGMP-dependent protein kinase anchoring protein) has been identified [].The N-terminal 66 amino acids of cGK-Ialpha were shown to be sufficient for association with GKAP42, but GKAP42 did not interact with cGK-Ibeta, cGK-II or cAMP-dependent protein kinase [
]. GKAP42 mRNA is specifically expressed in testis, where it is restricted to spermatocytes and early-round spermatids []. GKAP42 is believed to function as an anchoring protein for cGK-Ialpha, and it is thought that cGK-Ialpha may participate in germ-cell development through phosphorylation of Golgi-associated proteins such as GKAP42 [].A recurring chromosomal aberration in acute myeloid leukemia (AML) is deletion of the long arm of chromosome 9, del(9q) [
]. The Commonly Deleted Region (CDR) has been defined to less than 2.4 Mb, and found to contain 7 known genes, including GKAP42. The results of mutation and expression analyses of these genes are consistent with a model of tumour suppression mediated by haploinsufficiency of critical genes in del(9q) AML.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
This entry contains the Agrobacterium tumefaciens Ti-plasmid TraG, it is responsible for conjugative transfer of the entire plasmid among Agrobacterium strains [
]. The protein is distantly related to the F-type conjugation system TraG protein. Both of these systems are examples of type IV secretion systems.Also in this entry is the type IV secretion system-coupling protein VirD4 from Bartonella henselae. Substrates for VirD4 include the effector proteins BepA-G, which when injected into the human host epithelial cells (HEC) brings about rearrangement of the HEC cytoskeleton, inhibition of apoptosis, and proinflammatory activation by nuclear factor NF-kappa-B [
].
This entry includes a lactate binding TRAP transporter TTHA0766 and related proteins []. TRAP transporters are a large family of solute transporters ubiquitously found in bacteria and archaea. They are comprised of a periplasmic substrate-binding protein (SBP; often called the P subunit) and two unequally sized integral membrane components: a large transmembrane subunit involved in the translocation process (the M subunit) and a smaller membrane of unknown function (the Q subunit). The driving force of TRAP transporters is provided by electrochemical ion gradients (either protons or sodium ions) across the cytoplasmic membrane, rather than ATP hydrolysis. This substrate-binding domain belongs to the type 2 periplasmic binding fold protein superfamily (PBP2). The PBP2 proteins are typically comprised of two globular subdomains connected by a flexible hinge and bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap [].
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
A-kinase anchor protein 9 (AKAP9, also known as AKAP 350) and pericentrin (pericentrin-B, kendrin) are large coiled-coil proteins found in mammalian centrosomes that serve to recruit structural and regulatory components including dynein and protein kinase [
,
]. These scaffold proteins contain a pericentrin-AKAP-450 centrosomal targeting (PACT) domain [].Mutations of AKAP9 cause long QT syndrome 11 (LQT11), which is a heart disorder characterised by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias [
]. AKAP9 has also been implicated in breast cancer [] and sporadic papillary thyroid carcinomas []. In mice, AKAP9 is essential for Spermatogenesis and sertoli cell maturation [].
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 L5, ~180 amino acids in length, is one of the proteins from the large ribosomal subunit. In Escherichia coli, L5 is known to be involved in binding 5S RNA to the large ribosomal subunit. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities [
,
,
], groups:Eubacterial L5.Algal chloroplast L5.Cyanelle L5.Archaebacterial L5.Mammalian L11.Tetrahymena thermophila L21.Dictyostelium discoideum (Slime mold) L5Saccharomyces cerevisiae (Baker's yeast) L16 (39A).Plant mitochondrial L5.This entry represents the archaeal L5 proteins.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Members of this protein family are the TolB periplasmic protein of Gram-negative bacteria. TolB is part of the Tol-Pal (peptidoglycan-associated lipoprotein) multiprotein complex, comprising five envelope proteins, TolQ, TolR, TolA, TolB and Pal, which form two complexes. The TolQ, TolR and TolA inner-membrane proteins interact via their transmembrane domains. The β-propeller domain of the periplasmic protein TolB is responsible for its interaction with Pal. TolB also interacts with the outer-membrane peptidoglycan-associated proteins Lpp and OmpA. TolA undergoes a conformational change in response to changes in the proton-motive force, and interacts with Pal in an energy-dependent manner. The C-terminal periplasmic domain of TolA also interacts with the N-terminal domain of TolB. The Tol-PAL system is required for bacterial outer membrane integrity. Escherichia coli TolB is involved in the tonB-independent uptake of group A colicins (colicins A, E1, E2, E3 and K), and is necessary for the colicins to reach their respective targets after initial binding to the bacteria. It is also involved in uptake of filamentous DNA. Study of its structure suggests that the TolB protein might be involved in the recycling of peptidoglycan or in its covalent linking with lipoproteins. The Tol-Pal system is also implicated in pathogenesis of E. coli, Haemophilus ducreyi, Salmonella enterica and Vibrio cholerae, but the mechanism(s) is unclear.
This entry describes the inner membrane protein TolR, part of the TolR/TolQ complex that transduces energy from the proton-motive force, through TolA, to an outer membrane complex made up of TolB and Pal (peptidoglycan-associated lipoprotein). The complex is recruited to cell division sites and is required to maintain outer membrane integrity; defects may cause a defect in the import of some organic compounds. TolR is related to MotB, the peptidoglycan (PG)-binding stator protein from the flagellum, suggesting it might serve a similar role in Tol-Pal [
].
This very small protein (about 46 amino acids) consists largely of a single predicted membrane-spanning region. It is found in Photobacterium profundum SS9 and in three species of Vibrio, always near periplasmic nitrate reductase genes, but far from the periplasmic nitrate reductase genes in Aeromonas hydrophila ATCC 7966.
MAMLD1 (also called CXorf6) transactivates the promoter of Hes3 (a noncanonical Notch target gene hairy/enhancer of split 3), augments testosterone production, and contains the SF1(steroidogenic factor 1) target sequence [
].
Tetratricopeptide repeat protein 8 (TTC8, also known as BBS8) is part of the BBSome complex (BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10), which is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia [
]. The ciliary trafficking function of the BBSome is regulated by LZTFL1 (Leucine-zipper transcription factor-like 1) [].Primary cilia are ubiquitous cellular appendages that provide important sensory and signalling functions and their dysfunction underlies numerous human genetic disorders. The proteins disrupted in the human ciliary disorder Bardet-Biedl syndrome (BBS) are required for the localisation of G protein-coupled receptors to primary cilia on central neurons. The alteration of signalling caused by mislocalisation of ciliary signalling proteins underlies the BBS phenotype [
]. BBS8 is one of the genes involved in BBS. A splice-site mutation in TTC8/BBS8 is also known to cause nonsyndromic retinitis pigmentosa (RP) [].
This protein family consist of CLN5 and CLN5-like proteins. Defects in CLN5 are the cause of neuronal ceroid lipofuscinosis type 5 (CLN5), also known as Finnish variant late-infantile neuronal ceroid lipofuscinosis (vLINCL). Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterised by intracellular accumulation of autofluorescent liposomal material [
,
,
,
,
,
,
,
].
Bardet-Biedl syndrome is characterised by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation [
]. Bardet-Biedl syndrome proteins (BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10) form the BBSome complex, which may function as a coat complex required for sorting of specific membrane proteins to the primary cilia []. The ciliary trafficking function of BBSome is regulated by LZTFL1 (Leucine-zipper transcription factor-like 1) [].Primary cilia are ubiquitous cellular appendages that provide important sensory and signalling functions and their dysfunction underlies numerous human genetic disorders. The proteins disrupted in the human ciliary disorder Bardet-Biedl syndrome (BBS) are required for the localisation of G protein-coupled receptors to primary cilia on central neurons. The alteration of signalling caused by mislocalisation of ciliary signalling proteins underlies the BBS phenotype [
]. Of the 12 known BBS genes, BBS1 is the most commonly mutated [].This entry represents BBS1.
EPSTI1 is highly expressed in breast cancer upon interaction between tumor cells and stromal cells in vitro. It is expressed in blood mononuclear cells from patients with systemic lupus erythematosus (SLE) [
,
].
Hypoxia-inducible lipid droplet-associated protein
Type:
Family
Description:
Hypoxia-inducible lipid droplet-associated protein (HILPDA), also known as hypoxia-inducible protein 2 (HIG2), increases intracellular lipid accumulation. It stimulates expression of cytokines including IL6, MIF and VEGFA. It also enhances cell growth and proliferation [
,
]. Human HILPDA is highly expressed in renal cell carcinoma cells but barely detectable in adjacent normal kidney tissue. It is detected in some cervical and endometrial cancers [,
,
].
Mouse CKAP2 has been shown to possess microtubule stabilising properties [
] and is involved in regulating aneuploidy, cell cycle, and cell death in a p53-dependent manner []. In human, CKAMP2 is up-regulated in primary gastric cancers []. It has been shown that human CKAP2 is degraded by APC/C-Cdh1 during mitotic exit and that a tight regulation of CKAP2 protein level is important for mitotic progression [].
This is a superfamily of proteins from single-stranded DNA bacteriophages. Scaffold proteins B and D are required for procapsid formation. Sixty copies of the internal scaffold protein B are found in the procapsid [
].
DNA repair protein RecN is thought to be
DNA damage inducible and involved in recombinational processes. The N-terminal region of most of the bacterial RecN proteins sequenced to date contains an ATP/GTP binding domain within an SMC-like motif.SMC-like domains are involved in chromosomal scaffolding and segregation. It is possible that the function of RecN in homologous recombination is either
structural or enzymatic or both. RecN may be involved in the proper positioning of the recombining segments of DNA, ensuring normal recombination. Theobservation that inactivation of this gene leads to a decreased transformation efficiency, as well as increased sensitivity to DNA-damaging agents, may be due to
some defect in chromosomal partitioning or positioning during these recombination-dependent processes []. The protein may function presynapticallyto process double-stranded breaks to produce 3 single-stranded DNA
intermediates during recombination.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Bardet-Biedl syndrome is a member of genetic ciliopathies, but the link between cilia/centrosome deficits and metabolic abnormalities is not completely clear [
]. Bardet-Biedl syndrome (BBS) is a heterogeneous genetic disorder characterised by many features, including retinal degeneration, obesity, cognitive impairment, polydactyly, renal abnormalities, and hypogenitalism. BBS genes play an important role in maintaining leptin sensitivity in proopiomelanocortin neurons []. A relatively high incidence of BBS is found in the mixed Arab populations of Kuwait and in Bedouin tribes throughout the Middle East, most likely due to the high rate of consaguinity in these populations and a founder effect.Primary cilia are ubiquitous cellular appendages that provide important sensory and signalling functions and their dysfunction underlies numerous human genetic disorders. The proteins disrupted in the human ciliary disorder Bardet-Biedl syndrome (BBS) are required for the localisation of G protein-coupled receptors to primary cilia on central neurons. The alteration of signalling caused by mislocalisation of ciliary signalling proteins underlies the BBS phenotype [
]. Of the 12 known BBS genes, BBS1 is the most commonly mutated [].This entry represents BBS2, which is required for leptin receptor signalling in the hypothalamus [
]. BBS2 and 4 are also required for the localisation of somatostatin receptor 3 and melanin-concentrating hormone receptor 1 into neuronal cilia [].
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
This entry includes Armadillo repeat-containing protein 1 (ARMC1) may play a role in determining mitochondrial length, distribution and motility and, therefore, may regulate mitochondrial dynamics. It may act in association with mitochondrial contact site and cristae organizing system (MICOS) complex components and mitochondrial outer membrane sorting assembly machinery (SAM) complex components [
].
This family consists of sodium-dependent phosphate transport proteins of the solute carrier family SLC34A [
]. It includes mammalian type II renal Na+/Pi-cotransporters and other proteins from lower eukaryotes and bacteria, some of which are also Na+/Pi-cotransporters. In kidneys these proteins may be involved in actively transporting phosphate into cells via Na+ cotransport in the renal brush border membrane [].
This entry represents a group of kinase associated protein phosphatases from plants, including KAPP (also known as protein phosphatase 2C 70) from Arabidopsis. KAPP dephosphorylates the Ser/Thr receptor-like kinase RLK5 [
].
AbgT catalyzes the concentration-dependent uptake of p-aminobenzoyl-glutamate (PABA-GLU) into cells. This allows accumulation of PABA-GLU to a concentration enabling AbgAB to catalyze cleavage into p-aminobenzoate and glutamate [
].
This entry represents a group of malic acid transport proteins from fungi. In fission yeast it serves as a permease for malate and other C4 dicarboxylic acids [
].
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Gas vesicles are small, hollow, gas filled protein structures found in several cyanobacterial and archaebacterial microorganisms [
]. They allow thepositioning of the bacteria at the favorable depth for growth. Gas vesicles
are hollow cylindrical tubes, closed by a hollow, conical cap at each end.Both the conical end caps and central cylinder are made up of 4-5 nm wide
ribs that run at right angles to the long axis of the structure. Gas vesiclesseem to be constituted of two different protein components: GVPa and GVPc.
GVPc is a minor constituent of gas vesicles and seems to be located on theouter surface. Structurally, cyanobacterial GVPc consists of four or five
tandem repeats of a 33 residue sequence flanked by sequences of 18 and 10residues at the N- and C-termini, respectively.
Tgi2PP from Pseudomonas protegens is part of the Tge2PP- Tgi2PP Effector-immunity pair secreted by the type VI secretion system (T6SS). Tgi2PP interacts predominantly by hydrogen bonding and hydrophobic interactions with Tge2PP via the insertion of the β-sheet core of Tgi2PP into the substrate-binding groove of Tge2PP. Tgi2PP contains a similar topology to the periplasmic E. coli colicin M immunity protein [
].
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any functionA related protein (
) from Methanopyrus kandleri has this domain fused to the ProFAR isomerase (
) domain.
The MreD (murein formation D) protein is involved in bacterial cell shape determination [
,
]. Most rod-shaped bacteria depend on MreB and RodA to achieve either a rod shape or some other non-spherical morphology such as coil or stalk formation. MreD is encoded in an operon with MreB, and often with RodA and PBP-2 as well. It is highly hydrophobic (therefore somewhat low-complexity) and highly divergent, and therefore cannot always be identified on the basis of sequence similarity.
This entry represents the alpha crystallin domain (ACD) found in heat shock protein beta-3 (HspB3) from vertebrates, also known as heat-shock protein 27-like protein (HSPL27, 17kDa) [
,
]. Small heat shock proteins (sHSP) are molecular chaperones that suppress protein aggregation and protect against cell stress, and are generally active as large oligomers consisting of multiple subunits []. HspB3 is expressed in adult skeletal muscle, smooth muscle, and heart, and in several other fetal tissues. In muscle cells HspB3 forms an oligomeric 150kDa complex with myotonic dystrophy protein kinase-binding protein (MKBP/ HspB2), this complex may comprise one of two independent muscle-cell specific chaperone systems. The expression of HspB3 is induced during muscle differentiation controlled by the myogenic factor MyoD [
]. HspB3 may also interact with Hsp22 (HspB8).
