L10-interacting MYB domain-containing protein (LIMYB) is a transcriptional repressor that associates with ribosomal protein promoters [
]. It interacts with NIK1, a leucine-rich repeat receptor-like kinase (LRR-RLK), the virulence target of the begomovirus nuclear shuttle protein, leading to global translation suppression as an antiviral immunity strategy in plants [].
Lsb5 plays important roles in membrane-trafficking events through association with the actin regulators, the yeast Wiskott-Aldrich syndrome protein (WASP) homologue Las17 and the cortical protein Sla1, the yeast Arf3 (orthologous with mammalian Arf6), and ubiquitin. Lsb5 contains an N-terminal VHS (Vps27p/Hrs/STAM)-domain and a GAT (GGA and TOM1) domain. In contrast to GGA proteins, Lsb5 harbours a C-terminal NPF (Asn-Pro-Phe) motif, but does not have either a GAE (gamma-adaptin ear homology) domain or a clathrin-binding motif [
,
,
].
Developmentally regulated G-proteins (DRGs) are a highly conserved family of GTP-binding proteins found in archaea, plants, fungi and animals, indicating important roles in fundamental pathways. DRG is a member of the Obg family, an evolutionary branch of GTPase superfamily proteins. GTPases act as molecular switches regulating diverse cellular processes. DRG2 and DRG1 comprise the DRG subfamily in eukaryotes. It has been proposed that the DRG subfamily proteins play their physiological roles through RNA binding [
].
This family is secreted by Gram-negative Gammaproteobacteria such as Pseudomonas syringae of tomato and Erwinia amylovora (Fire blight bacteria), amongst others. It is an essential pathogenicity factor of approximately 198kDa. Its injection into the host-plant is dependent upon the bacterial type III or Hrp secretion system [
]. The family is long and carries a number of predicted functional regions, including an ERMS or endoplasmic reticulum membrane retention signal at both the C- and the N termini, a leucine-zipper motif from residues 539-560, and a nuclear localisation signal at 1358-1361. This conserved AvrE-family of effectors is among the few that are required for full virulence of many phytopathogenic pseudomonads, erwinias and pantoeas [].A double β-propeller structure is found towards the N terminus [
]. Furthermore, AvrE1, an AvrE-family T3E from Pseudomonas syringae pv. tomato strain DC3000, associates with specific PP2A B- subunit proteins from its susceptible host Arabidopsis. In a similar fashion, the WtsE (AvrE-family T3E from the maize pathogen Pantoea stewartii subsp. Stewartii) has been shown to target maize protein phosphatase 2A (PP2A) heterotrimeric enzyme complexes via direct interaction with B- regulatory subunits. Taken together, it has been indicated that that sub-component specific PP2A complexes are targeted by bacterial T3Es, including direct targeting by members of the widely conserved AvrE-family. Additionally, DspE, a type-III effector encoded by the broad-host-range bacterial soft-rot pathogen Pectobacterium carotovorum subsp. carotovorum (Pcc), has been indicated to be required and sufficient for disease-associated cell death in host plants [].
This entry represents bacterial proteins that are typically between 173 and 191 amino acids in length. PixA is thought to be specifically produced in Xenorhabdus nematophila. It is an inclusion body protein [
]. This entry also matches AidA.
This entry represents a group of F-box only proteins, including FBXO31/39 from humans and HAWAIIAN SKIRT (At3g61590) from Arabidopsis.
HAWAIIAN SKIRT (HWS; At3G61590) is a F-box dependent factor involved in miRNA function []. Loss of function of HWS exhibits pleiotropic phenotypes including sepal fusion [].F-box only protein 31 is a component of the SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in G1 arrest following DNA damage. It specifically recognises phosphorylated cyclin-D1 (CCND1), promoting its ubiquitination and degradation by the proteasome, resulting in G1 arrest [
,
].
This entry represents a group of PITH domain-containing proteins, including PITHD1 from animals. PITHD1 acts as an activator of an internal ribosome entry site (IRES) element in the RUNX1 gene and enhances RUNX1 expression that subsequently promoted megakaryocyte differentiation
[].
This superfamily represents a domain found in different pollen allergen proteins and in uncharacterised proteins from Oryza sativa (rice) including OsI_031781 and OsI_030282.Allergies are hypersensitivity reactions of the immune system to specific substances called allergens (such as pollen, stings, drugs, or food) that, in most people, result in no symptoms. A nomenclature system has been established for antigens (allergens) that cause IgE-mediated atopic allergies in humans [WHO/IUIS Allergen Nomenclature Subcommittee King T.P., Hoffmann D., Loewenstein H., Marsh D.G., Platts-Mills T.A.E., Thomas W. Bull. World Health Organ. 72:797-806(1994)]. This nomenclature system is defined by a designation that is composed of the first three letters of the genus; a space; the first letter of the species name; a space and an arabic number. In the event that two species names have identical designations, they are discriminated from one another by adding one or more letters (as necessary) to each species designation.Proteins in this family belong to the Poa p (Poa pratensis or Kentucky bluegrass) IX and Phl p (Phleum pratense) VI allergen family, and include allergens with the following designations: Lol p 5, Pha a 5, Phl p 6, and Poa p 9. Phl p 5b has been shown to possess ribonuclease activity [
]. Grass pollen allergens are one of the major causes of type I allergies (including allergic rhinoconjunctivitis, allergic bronchial asthma and hayfever), afflicting 15-20% of a genetically predisposed population []. These allergens exhibit an entirely α-helical structure with a four-helical bundle topology [
].
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 [].This entry contains the PknD family of serine/threonine protein kinases which are found in (for example) C. trachomatis. In conjunction with Pkn1 they may play a role in specific interactions with host proteins during intracellular growth [
].
Coq7 (also known as Clk-1 and CAT5) is a di-iron carboxylate protein occuring in both prokaryotes and eukaryotes that is essential for ubiquinone biosynthesis [
,
]. It has been implicated in the aging process as mutations in the Caenorhabditis elegans gene lead to increased lifespan []. Coq7 is a membrane-bound protein that functions as a monooxygenase to hydroxylate demethoxyubiquinone (DMQ or 2-methoxy-5-methyl-6-polyprenyl-1,4-benzoquinone) in the penultimate step of ubiquinone biosynthesis []. Biochemical studies indicate that NADH can serve directly as a reductant for catalytic activation of dioxygen and substrate oxidation by the enzyme, with no requirement for an additional reductase protein component []. This direct reaction with NADH is so far unique amongst members of the di-iron carboxylate protein family.
This superfamily represents the C-terminal domain of the ribosomal protein L20. The C-terminal domain of this protein is an α-helical domain. It specifically recognizes RNA [
].The ribosomal protein family L20, from the large (50S) subunit, contains members from eubacteria, as well as their mitochondrial and plastid homologs. L20 is an assembly protein, required for the first in vitro reconstitution step of the 50S ribosomal subunit, but does not seem to be essential for ribosome activity. L20 has been shown to partially unfold in the absence of RNA, in regions corresponding to the RNA-binding sites. L20 represses the translation of its own mRNA via specific binding to two distinct mRNA sites, in a manner similar to the L20 interaction with 23S ribosomal RNA [
,
,
,
,
,
,
].
This entry describes a family of long proteins, over 1250 amino acids in length and present in the Proteobacteria. The degree of sequence similarity is low between sequences from different genera. Apparent membrane-spanning regions at the N terminus and C terminus suggest the protein is inserted into (or exported through) the membrane.
Ribosomal protein L7, which is found in archaea and eukaryotes but not in prokaryotes, binds domain II of the 23S rRNA, as well as the 5S rRNA, and is one of five ribosomal proteins that mediate the interactions 5S rRNA makes with the ribosome. The eukaryotic L7 members have an N-terminal extension not found in the archeal L7 orthologues. L7 is closely related to the ribosomal L30 protein found in eukaryotes and prokaryotes [
,
].This domain is also found in ribosome biogenesis protein RLP7, which is a homologue of L7 [
].
Poly-beta-1,6-N-acetyl-D-glucosamine biosynthesis protein PgaD
Type:
Family
Description:
This entry represents the poly-beta-1,6-N-acetyl-D-glucosamine (PGA) biosynthesis protein PgaD. This cytoplasmic membrane protein appears to be an auxiliary subunit to the PGA synthase PgaC (
) [
,
,
]. PgaD is esential for the process of PGA synthesis and export. PGA serves as an adhesin for the maintenance of biofilm structural stability in bacteria.
This entry describes a small protein of unknown function, about 100 amino acids in length, essentially always found in an operon with CydAB, subunits of the cytochrome d terminal oxidase. It appears to be an integral membrane protein. It is found so far only in the Proteobacteria [
].
This protein family is restricted to the Prochlorococcus and Synechococcus lineages of the Cyanobacteria, and is sporadic in those lineages. Members average 100 amino acids in length, including a 30-residue, highly polar, low complexity region sandwiched between an N-terminal region of about 60 residues and a C-terminal [KR]VVR[KR]RS motif, both well-conserved. Their function is unknown.
Members of this protein family are uncharacterised. The only invariant residue, and one of three other residues better than 90 percent conserved are both Cys. Phylogenetic profiling results and occasional fusion genes suggest a role for members of this family in redox reactions or iron cluster metabolism. Species occasionally have two or three copies.
Members of this rare protein family occur in the presence of
and
, which in turn occur only in the context of radical SAM protein families
and
. Their function is unknown.
Isochorismate pyruvate-lyase (IPL; PchB) catalyses the second reaction in the pyochelin biosynthetic pathway of Pseudomonas aeruginosa, conversion of isochorismate to salicylate plus pyruvate (following the initial PchA-dependent conversion of chorismate to isochorismate) [
]. This enzyme can also carry out the chorismate mutase (CM) reaction, but with a low catalytic efficiency. It is unlikely that PchB plays a significant role in aromatic amino acid biosynthesis. This enzyme is a stand-alone version of a chorismate mutase domain of the AroQ class.The three types of CM are AroQ class, prokaryotic type; AroQ class, eukaryotic type; and AroH class. They fall into two structural folds (AroQ class and AroH class) which are completely unrelated [
]. The two types of the AroQ structural class (the Escherichia coli CM dimer and the yeast CM monomer) can be structurally superimposed, and the topology of the four-helix bundle forming the active site is conserved [].The PchB-type of chorismate mutase domain, while sharing conserved residues and the predicted secondary structure with the other subgroups of the AroQ class (prokaryotic type), has isochorismate pyruvate-lyase (IPL) as a primary catalytic activity. PchB can still use the same active site either for the IPL or for the CM reaction. It has been suggested that PchB was derived from an AroQ-class CM by a gene duplication event followed by selection for efficient IPL function in the course of the evolution of the pyochelin siderophore pathway, with only residual CM activity remaining. It can be further speculated that contemporary CMs may already possess (weak) IPL activity [
].For additional information please see [
,
,
].
The adaptor protein 3BP2/SH3BP2 is a cytoplasmic adaptor that contributes to the regulation of immune responses [
]. The protein-tyrosine kinase Syk phosphorylates 3BP2 which results in the activation of Rac1 through the interaction with the SH2 domain of Vav1 and induces the binding to the SH2 domain of the upstream protein-tyrosine kinase Lyn and enhances its kinase activity []. 3BP2 has a positive regulatory role in IgE-mediated mast cell activation []. In lymphocytes, engagement of T cell or B cell receptors triggers tyrosine phosphorylation of 3BP2 []. 3BP2 is required for the proliferation of B cells and B cell receptor signaling. Mutations in the 3BP2 gene are responsible for cherubism resulting in excessive bone resorption in the jaw [].
This family consists of the 40 members of a paralogous protein family in the rumen anaerobe Fibrobacter succinogenes S85, and a smaller number in Bdellovibrio bacteriovorus HD100. Member proteins are about 270 residues long and appear to lack signal sequences and transmembrane helices. The only perfectly conserved residue is a glycine in an otherwise poorly conserved region, suggesting members are not enzymes. The family is not characterised.
This entry represents a group of WD repeat-containing proteins, including Ipi3 from yeasts, WDR18 from animals and RID3 from Arabidopsis. Ipi3 is part of the Rix1 complex required for the processing of 35S pre-rRNA in pre-60S ribosomal particles and for the initiation of DNA replication [
]. It interacts with pre-RC proteins, binds chromatin predominantly at ARS sequences in a cell cycle-regulated and ORC- and Noc3-dependent manner []. WDR18, the human Ipi3 homologue, is a component of the Five Friends of Methylated CHTOP (5FMC) complex, which is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes []. It is also involved in human DNA replication licensing [,
]. RID3 acts as negative regulator of the CUC-STM pathway in shoot apical meristem (SAM) neo-formation [].
Pentatricopeptide repeat-containing protein At1g15510-like
Type:
Family
Description:
This entry represents a group of plant pentatricopeptide repeat-containing proteins, including At1g15510, At3g16610 and At2g39620. The PPR proteins have been proposed to contact the RNA sequence with selected repeats at specific nucleotides [
]. At1g15510 also known as Protein EARLY CHLOROPLAST BIOGENESIS 2, regulates the RNA editing of the chloroplast transcript accD, and is essential for the early stages of chloroplast biogenesis [,
,
]. It is required for the RNA editing of the chloroplast transcript ndhF [,
].
BMP/retinoic acid-inducible neural-specific protein
Type:
Family
Description:
This entry represents the BMP/retinoic acid-inducible neural-specific protein (BRINP) family, including BRINP1/2/3. They are predominantly and widely expressed in both the central nervous system (CNS) and peripheral nervous system (PNS). They inhibit neuronal cell proliferation by negative regulation of the cell cycle G1/S transition [,
].
Rrp5 is involved in the biogenesis of rRNA. It is required for formation of both 18S and 5.8S rRNA in budding yeasts [
]. In humans it is also known as NFBP, which is essential for the generation of 18S rRNA []. In Arabidopsis it is essential for normal development of female gametophytes [].
This entry represents a group of maestro heat-like repeat-containing proteins, including protein Maestro and SPIF from animals, and SGR6 from Arabidopsis. They contain HEAT repeats motif or regions that are highly similar to HEAT repeats.Maestro (Male-specific Transcription in the developing Reproductive Organs (MRO)) is expressed in human granulosa cumulus cells and in testicular germ cells [
]. SPIF may play a role in the process of sperm capacitation [].SGR6 (SHOOT GRAVITROPISM6) is a membrane-associated protein involved in the formation and/or maintenance of invaginated vacuolar membrane structures in gravity-sensing cells [
].
This entry includes RanGAP1/2 mostly from plants. They are GTPase activators for the nuclear Ras-related regulatory protein Ran, converting it to the putatively inactive GDP-bound state [
]. RanGAP1 may have a role in spatial signaling during plant cell division [].
This entry represents PylC, which is part of a three-gene cassette that directs the biosynthesis of pyrrolysine, the twenty-second amino acid, that is incorporated in some species at a UAG canonical stop codon [
]. The radical S-adenosyl-L-methionine (SAM) protein PylB mediates a lysine mutase reaction that produces 3-methylornithine, which is then ligated to a second molecule of lysine by PylC before oxidation by PylD results in pyrrolysine [].
Members of this protein family are uncharacterised and contain two copies of the cyclic nucleotide-binding domain. Members are restricted to select cyanobacteria but are found regularly in association with a transport operon that, in turn, is associated with the production of putative bacteriocins. This suggests a possible role as a bacteriocin-type transport-associated protein.
This entry represents SdpB, an integral membrane protein associated with production of the cannibalism peptide SdpC in Bacillus subtilis [
], and related proteins. Similar proteins are found in Myxococcus xanthus.
GHITM (also known as MICS1) appears to be ubiquitiously expressed in mammalian cells and expression has also been observed in various cancer cell lines [
]. It is involved in maintenance of mitochondrial morphology and apoptotic release of cytochrome c []. It is closely related to the BAX inhibitor (BI)-1 like family of small transmembrane proteins, which have been shown to have an anti-apoptotic effect [,
,
].
This entry represents a group of RanGTP-binding proteins that contain a conserved RanGTP-binding motif, also called a Ran-binding domain (RBD). They have been implicated in nucleocytoplasmic transport. NUP358 (RanBP2) is localised to the cytoplasmic filaments protruding from the nuclear pore complex (NPC) into the cytoplasm, while RanBP3/Hba1 are localised to the nucleoplasm and Nup2 is localised to the NPC. In general, RanBP1 and other members of this protein family increase, via their conserved RBDs, the rate of RanGAP1-mediated GTP hydrolysis on Ran [
].
This entry includes Rna14 from yeasts, protein suppressor of forked (su(f)) from Drosophila melanogaster, CSTF3 from animals and CstF77 from Arabidopsis. In budding yeasts, Rna14 is part of the cleavage factor I A (CF IA) complex and is required for both the cleavage and polyadenylation activities of CF IA [
]. Protein suppressor of forked may have similar function [,
]. CstF77 is involved in floral repressor gene (FLC) silencing [].
This entry represents a group of zinc finger proteins, including MBS1/2 from Arabidopsis and ZNF706 from animals. MBS1/2 are required for induction of singlet oxygen-dependent gene expression and is involved in ROS signalling [
]. ZNF706 may act as a transcription repressor involved in the exit of embryonic stem cells (ESCs) from self-renewal []. MBS1 is involved in the singlet oxygen signalling downstream of beta-cyclocitral [
].
This entry represents a group of plant cytokinin-induced F-box proteins, including At2g27310, At3g44326 and At2g36090 from Arabidopsis. AT3G44326, also known as CFB, is expressed in all plant tissues, predominantly in root tissue [
].
This entry represents a group of plant zinc finger proteins, including CONSTANS and related proteins. CONSTANS is a transcription factor that acts in the long day flowering pathway and may mediate between the circadian clock and the control of flowering [
,
]. This entry also includes rice Ghd7 and CO3, which also control rice flowering [,
].
CCDC39 is an axonemal protein with coiled-coil domains required for assembly of inner dynein arms and the dynein regulatory complex, a key regulator of motor activity in cilia [
]. Mutations in CCDC39 are a cause of primary ciliary dyskinesia, a disorder caused by cilia and sperm dysmotility [].
Dehydration-responsive element-binding protein 1A-I
Type:
Family
Description:
This entry represents a group of plant DREB1/CBF-type transcription factors, including DREB1A-I from rice. They interact with the DRE/CRT cis-acting element and control the expression of many stress-inducible genes [
,
,
].
This entry represents a group of receptor-like protein kinase mostly from plants, including ANXUR1/2 (ANX1/2), FERONIA (FERON), HERCULES1(HERK1) and THESEUS 1 (THE1) from Arabidopsis. ANX1 and ANX2 are male factors that control pollen tube behaviour by directing rupture at proper timing [
,
,
]. THESEUS 1 is required for cell elongation during vegetative growth, mostly in a brassinosteroid-(BR-) independent manner [].
FtsN is a poorly conserved protein active in cell division in a number of Proteobacteria. The N-terminal 30 residue region tends to by Lys/Arg-rich, and is followed by a membrane-spanning region. This is followed by an acidic low-complexity region of variable length and a well-conserved C-terminal domain of two tandem regions (Sporulation related repeat), found in several cell division and sporulation proteins. The role of FtsN as a suppressor for other cell division mutations is poorly understood; it may involve cell wall hydrolysis [].
This family consists of proteins over 500 amino acids long in Caenorhabditis elegans and several bacteria (Pseudomonas aeruginosa, Anabaena sp. (strain PCC 7120), Leptospira interrogans, etc.). The function is unknown.
Members of this uncharacterised protein family share a histidine/serine-rich cluster, typically H-R-S-H-S-S-H-R-S-H-S-S-H. Members are found always in the context of a pair of radical SAM proteins, HxsB and HxsC, and a fourth protein HxsD. The system is predicted to perform peptide modifications, likely in the His-Xaa-Ser region, to produce some uncharacterised natural product.
Members of this family include SbnA, a protein of the staphyloferrin B biosynthesis operon of Staphylococcus aureus. SbnA and SbnB together appear to synthesize 2,3-diaminopropionate, a precursor of certain siderophores and other secondary metabolites. SbnA uses PLP and substrates O-phospho-L-serine and L-glutamate to produce a metabolite N-(1-amino-1-carboxyl-2-ethyl)-glutamic acid (ACEGA), while SbnB uses NAD(+) to oxidatively hydrolyze ACEGA to yield alpha-ketoglutarate and L-Dap [
].
This entry represents PylD, which is part of a three-gene cassette that directs the biosynthesis of pyrrolysine, the twenty-second amino acid, that is incorporated in some species at a UAG canonical stop codon [
].
Cell division in bacteria is a complex process driven by the septal ring, a membrane-associated cytoskeletal element that directs the formation of the septum [
]. Central to formation of the septal ring, and hence cell division itself, is the tubulin-like GTPase protein FtsZ which is the first cell division component to specifically accumulate at the division site. Here it self-assembles into a ring-like polymer structure associated with the inner surface of the cytoplasmic membrane, providing a scaffold to recruit other members of the septal ring.This entry represents the bacterial cell division protein ZipA. ZipA is one of the first proteins recruited to the division site after FtsZ, which it directly binds, and is essential for cell division and viability in Escherichia coli. ZipA has been shown to The protein contains five distinct regions. The N terminus contains a short hydrophobic regions which anchors the protein to the cytoplasmic membrane. This is followed by short basic and acidic regions, and a longer proline-rich region. The C-terminal domain interacts with FtsZ through hydrophobic interactions involving exposed non-polar residues, and forms a six-stranded beta sheet packed against three alpha helices [
,
]. Since ZipA is anchored to the cytoplasmic membrane while binding FtsZ, it has been speculated that the function of ZipA may be to link the membrane with the FtsZ rings, to stabilise or organise the FtsZ rings, or to link invagination of the membrane to constriction of the FtsZ ring during septation. ZipA has been shown to induce association of FtsZ protofilaments into arrays of long thick bundles in vitro.
This entry represents SdpA and similar proteins that are found in Myxococcus xanthus, Stigmatella aurantiaca DW4/3-1, Streptomyces sp. ACTE, etc. SdpA is associated with production and export of the cannibalism peptide SdpC in Bacillus subtilis [
].
This entry describes a putative DNA packaging protein from bacteriophage 16-3, related proteins in other bacteriophage and prophage regions of bacterial genomes. Homologues are also found in Gene Transfer Agents (GTA) [
], including ORFg6 (RCAP_rcc01688) of the GTA of Rhodobacter capsulatus (Rhodopseudomonas capsulata) [see Fig.1, in ].
This family consists of a large, conserved hypothetical protein in phage tail-like regions of at least six bacterial genomes: Gloeobacter violaceus PCC 7421, Geobacter sulfurreducens PCA, Streptomyces coelicolor (strain A3(2)), Streptomyces avermitilis MA-4680, Rhizobium loti (Mesorhizobium loti), and Myxococcus xanthus. The function is unknown.
This entry represents proteins, which are about 135 amino acids in length and largely restricted to the Proteobacteria. This family and a delta5-3-ketosteroid isomerase from Pseudomonas testosteroni appear homologous, especially toward their respective N-termini. Members, therefore, probably are enzymes.
This conserved hypothetical protein of unknown function is predominantly found in proteobacteria. Its function is unknown and its genome context is not well-conserved. It is found amid urease genes in at least one species.
Toxoplasma gondii is an obligate intracellular apicomplexan protozoan
parasite, with a complex lifestyle involving varied hosts []. It has two phases of growth: an intestinal phase in feline hosts, and an extra-intestinal phase in other mammals. Oocysts from infected cats develop
into tachyzoites, and eventually, bradyzoites and zoitocysts in the extraintestinal host [
]. Transmission of the parasite occurs through contact with infected cats or raw/undercooked meat; in immunocompromised
individuals, it can cause severe and often lethal toxoplasmosis. Acute infection in healthy humans can sometimes also cause tissue damage [
].The protozoan utilises a variety of secretory and antigenic proteins to
invade a host and gain access to the intracellular environment []. These originate from distinct organelles in the T. gondii cell termed micronemes,
rhoptries, and dense granules. They are released at specific times during invasion to ensure the proteins are allocated to their correct target
destinations []. Dense granule antigens (GRAs) are released from the T. gondii tachyzoite
while still encapsulated in a host vacuole.Gra7, one of these moieties, is believed to be secreted by the parasite during the late phase of intra-vacuolar habitation [
]. Studies utilising immunogold labelling have localised Gra7 to the parasitophorous vacuolar membrane, and the network tubules formed by the Gra2/4/6 complex []. It has been suggested that dense granule antigens stimulate humoral immunity in the host []. A homologue of Gra7 is found in Neospora caninum.
The Saccharomyces cerevisiae pheromone response pathway involves a cascade of 3 MAP kinases Ste11, Ste7, and Fus3. Ste5 is an essential element of this cascade, acting as a scaffold for each of the MAP kinases prior to signalling [
]. This entry represents the Fus3-binding domain of Ste5, also known as the minimal scaffold domain. It acts as a co-catalyst, binding Fus3 and promoting its phosphorylation by Ste7 []. In the absence of this domain, Fus3 is an extremely poor substrate for Ste7. The requirement for both Ste7 and this domain in Fus3 activation ensures that Fus3 is selectively activated by the mating pathway and not by other pathways that also utilise Ste7.
The E3B 14.5kDa was first identified in human adenovirus type 5. It is an integral membrane protein oriented with its C terminus in the cytoplasm. It functions to down-regulate the epidermal growth factor receptor and prevent tumour necrosis factor cytolysis. It achieves this through the interaction with E3 10.4kDa protein [
,
].
Spermidine export protein MdtJ catalyzes the excretion of spermidine. It can also confer resistance to deoxycholate and SDS [
,
]. It is induced by spermidine.
Periodontal disease in humans is a major health problem in the developed
world, and is caused by a number of specialised pathogens that inhabit the oral cavity. Amongst the bacterial species culturable from periodontal
lesions are the streptococcal microbes Streptococcus mutans and Streptococcus sobrinus, and the Gram-negative anaerobe Porphyromonas gingivalis (Bacteroides gingivalis) [
]. The latter bacterium has been implicated as the causative agent of peridontitis, pulpal infections and tonsillar abcesses [].Adherence by P. gingivalis to the periodontal surface is mediated by its
major virulence factor fimbriae []. This differs from other pathogenic Gram-negative bacterial polymeric Type I and IV fimbriae/pili in that it is much more simplified, consisting of only a monomeric fimbrillin repeating subunit, Fma1/FimA. Fma1/FimA has a molecular weight of 43kDa, and can exhibit antigenic diversity in different P. gingivalis strains []. Unusually, this form of fimbrillin possesses a far longer leader peptide compared to the fimbrial subunits of other bacteria []. It has been hypothesised that this allows for the maturation of the preprotein during secretion [].Recently, a study into the different antigenic types of P. gingivalis
fimbrillin classified them into five distinct groups, depending on their gene sequences [
]. Investigations into the functional differences of each type revealed that in the majority of peridontitis cases, bacterial strains possessing the type II Fma1/FimA were the most prevalent []; in healthy adults, type I strains were the most common. This has implications for particular strains that are associated with periodontal disease.
Toxoplasma gondii is an obligate intracellular apicomplexan protozoan
parasite, with a complex lifestyle involving varied hosts []. It has two phases of growth: an intestinal phase in feline hosts, and an extra-intestinal phase in other mammals. Oocysts from infected cats develop
into tachyzoites, and eventually, bradyzoites and zoitocysts in the extraintestinal host [
]. Transmission of the parasite occurs through contact with infected cats or raw/undercooked meat; in immunocompromised
individuals, it can cause severe and often lethal toxoplasmosis. Acute infection in healthy humans can sometimes also cause tissue damage [
].The protozoan utilises a variety of secretory and antigenic proteins to
invade a host and gain access to the intracellular environment []. These originate from distinct organelles in the T. gondii cell termed micronemes,
rhoptries, and dense granules. They are released at specific times during invasion to ensure the proteins are allocated to their correct target
destinations []. Dense granule antigens (GRAs) are released from the T. gondii tachyzoite
while still encapsulated in a host vacuole.Gra6, one of these moieties, is associated with the parasitophorous vacuole [
]. It possesses a hydrophobiccentral region flanked by two hydrophilic domains, and is present as a
single copy gene in the Toxoplasma gondii genome []. Gra6shares a similar function with Gra2, in that it is rapidly targeted to a network of membranous tubules that connect with the vacuolar membrane [
]. Indeed, these two proteins, together with Gra4, form a multimeric complex that stabilises the parasite within the vacuole.
Toxoplasma gondii is an obligate intracellular apicomplexan protozoan
parasite, with a complex lifestyle involving varied hosts []. It has two phases of growth: an intestinal phase in feline hosts, and an extra-intestinal phase in other mammals. Oocysts from infected cats develop
into tachyzoites, and eventually, bradyzoites and zoitocysts in the extraintestinal host [
]. Transmission of the parasite occurs through contact with infected cats or raw/undercooked meat; in immunocompromised
individuals, it can cause severe and often lethal toxoplasmosis. Acute infection in healthy humans can sometimes also cause tissue damage [
].The protozoan utilises a variety of secretory and antigenic proteins to
invade a host and gain access to the intracellular environment []. These originate from distinct organelles in the T. gondii cell termed micronemes,
rhoptries, and dense granules. They are released at specific times during invasion to ensure the proteins are allocated to their correct target
destinations []. Dense granule antigens (GRAs) are released from the T. gondii tachyzoite
while still encapsulated in a host vacuole.Gra2, one of these moieties, is
rapidly targeted to a network of membranous tubules that connect with thevacuolar membrane [
]. A recent study into the exact mechanism of Gra2secretion has revealed that the secondary structure of the protein plays a
major role in its targeting and release from the apical pole of the parasitic cell [
]. Two amphipathic α-helical regions ensure not onlythat association of Gra2 with the host vacuole membrane takes place, but
also that it is correctly targeted to the cell posterior, where stabilisingnetworks of tubules form and hold the cell steady in the vacuole.
Sequence-specific single-strand DNA-binding protein
Type:
Family
Description:
The sequence-specific single-strand DNA-binding protein (SSDP) family is
thought to be involved in transciption regulation. SSDP specifically bindssingle-stranded pyrimidine-rich mirror repeat elements commonly found in
promoter regions, and is believed to regulate alpha-2(I) collagen [
]. Ithas been identified as a target for unbalanced translocations and deletions
in acute myelogenous leukemia cells, implying a role as a tumour suppressorgene. It is expressed in spleen, lymph node, peripheral blood, bone
marrow, thymus and foetal liver. Family members have been identified inchicken, human, rat, mouse and Drosophila. The highest sequence identity is
observed in the first 100 N-terminal residues, which contains a tryptophan-rich region in its centre. The C terminus is more viariable, with glycine/proline-rich low complexity regions.
Spermidine export protein MdtI catalyzes the excretion of spermidine. It can also confer resistance to deoxycholate and SDS [
,
]. It is integral to membrane [].
This family consists of several hypothetical proteins of unknown function from bacteria and L-cysteine desulfidases from the archaea Methanocaldococcus [
].
This entry represents a group of thioredoxin domain-containing proteins, including TXNDC17 from animals, SPBC21C3.12c from fission yeasts and AtClot from Arabidopsis. TXNDC17, also known as TRP14, 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 [
].
This family contains SPRY domain-containing protein 7 (also known as SPRY domain-containing protein 7, CLL deletion region gene 6 protein homologue, CLLD6 or chronic lymphocytic leukemia deletion region gene 6 protein homologue). In humans, CLLD6 is highly expressed in heart, skeletal muscle, and testis as well as cancer cell lines. It also has cross-species conservation, suggesting that it is likely to carry out important cellular processes [
,
].
This entry includes protein suppressor of sable (also known as Su(s)) from flies and related proteins from eukaryotes. They contain closely related CCCH zinc finger (ZF) motifs. Su(s) is a nuclear RNA-binding protein that inhibits the accumulation of certain aberrant mRNAs [
]. It has been shown to interact with Wdr82, and together they inhibit Pol II elongation through Hsp70-alphabeta elements [].
This entry represents a group of F-box only proteins, including FBXO9/48 from animals, Pof7/Hrt3 from yeasts and SKIP32 from plants.
Hrt3 is a substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins [
]. FBXO9 is a substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of TTI1 and TELO2 in a CK2-dependent manner, thereby directly regulating mTOR signalling []. GID2 (also known as SLEEPY 1) is an essential component of the SCF-type E3 ligase complex, SCF(GID2), a complex that positively regulates the gibberellin signalling pathway [].
Sad1/UNC-84 (SUN)-domain proteins are inner nuclear membrane (INM) proteins that are part of bridging complexes linking cytoskeletal elements with the nucleoskeleton. Originally identified based on an ~150-amino acid region of homology between the C terminus of the Schizosaccharomyces pombe Sad1 protein and the Caenorhabditis elegans UNC-84 protein, SUN proteins are present in the proteomes of most eucaryotes. In addition to the SUN domain, these proteins contain a transmembrane sequence and at least one coiled-coil domain and localise to the inner nuclear envelope. SUN proteins are anchored in the inner nuclear envelope by their transmembrane segment and oriented in the membrane such that the C-terminal SUN domain is located in the space between the inner and outer nuclear membrane. Here, the SUN domain can interact with the C-terminal tail of an outer nuclear envelope protein that binds to the cytoskeleton, including the centrosome [,
,
].
This entry includes a group of F-box-like/WD repeat-containing proteins, including Hif2/Sif2 from yeasts, Ebi from Drosophila melanogaster, TBL1X /TBL1XR1 from humans and HOS15 from Arabidopsis. Hif2/Sif2 is part of the set3 histone deacetylase complex involved in chromatin remodeling and transcription regulation [
]. Ebi promotes the degradation of a repressor of neuronal differentiation (Ttk88) and also limits S phase entry []. TBL1X /TBL1XR1 act as a bridge between the corepressor protein and histones by interacting with both of them within the complex. The N terminus of TBL1X interacts with the N termini of both H2B and H4 histones, and the first three C-terminal WD40-repeats of TBL1X interact with the corepressor complex [
]. TBL1X /TBL1XR1 serve as specific adaptors for the recruitment of the ubiquitin conjugating/19S proteasome complex [] and are important for both formation and dismantling of the NCOR complex, which is a corepressor complex. Mutations of the TBL1XR1 gene have been linked to several neurodevelopmental disorders, such as spanning from autism spectrum disorders (ASD), West syndrome, schizophrenia (SCZ), intellectual disability [
].HOS15 represses genes associated with abiotic stress tolerance through histone deacetylation in Arabidopsis
[].
SMU1 is a component of the spliceosome involved in pre-mRNA splicing [
]. In Arabidopsis SMU1 and SMU2 are required for low-Mg tolerance through regulating the pre-mRNA splicing of the Mg2+ transporter gene MRS2-7 []. In Caenorhabditis elegans SMU1 and SMU2 function together to regulate splice site choice in the pre-mRNAs of unc-52 and other genes [].
Dof domain is a zinc finger DNA-binding domain that shows resemblance to the Cys2 zinc finger, although it has a longer putative loop where an extra Cys residue is conserved [
]. Dof domain containing proteins are transcription factors that play various roles in plants [,
,
,
].
The YTH (YT521-B homology) domain has been suggested to be an evolutionarily conserved m6A-dependent RNA binding domain [
]. Proteins containing this domain includes mammalian YTHD and YTDC proteins, Arabidopsis CPSF30 (At1g30460), budding yeast Pho92 and fission yeast Mmi1. In Saccharomyces cerevisiae, Pho92 is a post-transcriptional regulator that regulates Pho4 mRNA stability by binding to the 3'-UTR in a phosphate-dependent manner. Its YTH domain exhibits RNA-binding activity [
]. In Schizosaccharomyces pombe, Mmi1 has been identified as eliminating meiosis-specific mRNAs []. Rat YTHDC1 (also known as YT521-B) is an alternative splicing regulator that recognises and binds N6-methyladenosine (m6A)-containing RNAs. The YTH domain of YT521-B is a RNA-binding domain with a very degenerate sequence-specificity [
].
RNPC3 serves as a bridging factor between the U11 and U12 snRNPs. It contains two RNA recognition motifs (RRMs), connected by a linker that includes a proline-rich region. It binds to the U11-associated 59K protein via its RRM1 and employs the RRM2 to bind hairpin III of the U12 small nuclear RNA (snRNA). The proline-rich region might be involved in protein-protein interactions [
,
]. RBM41 contains only one RRM. Its biological function remains unclear.
This entry represents a group of WD repeat-containing proteins, including DCAF7 from animals, LWD1/2/TTG1 from Arabidopsis and YPL247C from budding yeasts. In general, WD40 repeat domain-containing proteins are scaffolding elements for the assembly of multi-subunit protein complexes. DCAF7, also known as WDR68, interacts with Dual-specificity Tyrosine Phosphorylation-Regulated Kinase 1A (DYRK1A, a Down's syndrome-associated protein kinase) [
] and is required for Endothelin-1 (EDN1) signalling []. It also acts as a DDB1- and CUL4-associated factor []. Mutations in the DCAF7 gene have been linked to cleft lip with or without cleft palate (CL/P) []. In Arabidopsis, LWD1 and LWD2 serve as clock proteins involved in photoperiod flowering control []. TRANSPARENT TESTA GLABRA 1 (TTG1) is a regulator of early developmental traits and is also involved in flowering time regulation [].
This entry describes a family of conserved hypothetical proteins of small size with four invariant Cys residues. This small protein is distantly homologous to a C-terminal domain found in proteins identified by N-terminal homology as ribonucleotide reductases.
This motif appears in 29 copies in a large (greater than 10000 amino protein in Synechococcus sp. (strain WH8102) associated with a novel flagellar system, as one of three different repeats. Similar domains are found in two different large (less than 3500 amino acid) proteins of Synechocystis sp. (strain PCC 6803).
Copper sequestering activity displayed by some bacteria is determined by copper-binding protein products of the copper resistance operon (cop). CopD, together with CopC, perform copper uptake into the cytoplasm [
].
Chromosome segregation in eukaryotes requires the kinetochore, a multi-protein structure that assembles on centromeric DNA, and which acts to link chromosomes to spindle microtubules. Kinetochore structure and composition is highly conserved among vertebrates. The inner kinetochore is essential for kinetochore assembly, and is involved in chromosome segregation via regulation of the spindle. Inner kinetochore components include the multi-subunit CENP-H/I complex, which may function, in part, in directing centromere protein A (CENP-A) deposition to centromeres, where CENP-A is a centromere-specific histone H3 variant required for the organisation of centromeric chromatin during interphase. The CENP-H/I complex contains three functional classes of proteins [
,
]: CENP-H class (includes CENP-H, -I, -K, -L)CENP-M class (includes CENP-M)CENP-O class (includes CENP-O, -P, -Q, -R, -50)CENP-H is required for the localisation of CENP-C, but not CENP-A, to the centromere. However, it may be involved in the incorporation of newly synthesised CENP-A into centromeres via its interaction with the CENP-A/CENP-HI complex. CENP-H contains a coiled-coil structure and a nuclear localisation signal. CENP-H is specifically and constitutively localised in kinetochores throughout the cell cycle, and may play a role in kinetochore organisation and function throughout the cell cycle [
].Studies show that CENP-H may be associated with certain human cancers [
,
].This entry represents the C-terminal domain of CENP-H. Proteins containing this domain also include Schizosaccharomyces pombe Kinetochore protein Fta3, which is a subunit of the Sim4 complex. This complex is required for loading the DASH complex onto the kinetochore via interaction with dad1. Fta2, Fta3 and Fta4 associate with the central core and inner repeat region of the centromere [
].
This entry represents the protein phosphatase inhibitor 1 (IPP-1) family, which consists of PPP1R1A/B/C. They are involved in signal transduction and are endogenous inhibitors of protein phosphatase-1 [
]. PPP1R1B, also known as DARPP-32, has a key role in many neurotransmitter pathways throughout the brain and has been shown to be involved in controlling receptors, ion channels and other physiological factors including the brain's response to drugs of abuse, such as cocaine, opiates and nicotine. If phosphorylated, DARPP-32 can inhibit protein-phosphatase-1 []. DARPP-32 is reciprocally regulated by the two neurotransmitters that are most often implicated in schizophrenia - dopamine and glutamate. Dopamine activates DARPP-32 through the D1 receptor pathway and disables DARPP-32 through the D2 receptor. Glutamate, acting through the N-methyl-d-aspartate receptor, renders DARPP-32 inactive. A mutant form of DARPP-32 has been linked with gastric cancers [].
This entry represents a group of phage capsid/coat-related proteins, including Gp13 from Bacillus phage SPP1. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches. Gp13 is part of the icosahedral capsid together with the auxiliary protein gp12, which are organized in a T=7 lattice [
]. This family contains some conserved motifs: GD, GxxxxV/IxxD and NW.
This entry represents a domain in the C-terminal region of several F-box proteins in eukaryotes. These proteins are the substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Proteins containing this domain include the yeast Hrt3 protein [
,
] and human F-box only 9 protein (FBXO9) [].
LRP130 is a pentatricopeptide motif protein that binds to mitochondrial and nuclear RNAs [
]. It associates with mRNA/mRNP complexes at the outside of NE and ER, and plays a role in control of mRNA metabolism []. It may be involved in mitochondrial RNA transcript stability, transcription termination, and RNA processing []. Mutations in the LRP130 gene cause Leigh syndrome French-Canadian type (LSFC), which is a severe neurological disorder characterised by bilaterally symmetrical necrotic lesions in subcortical brain regions that is commonly associated with systemic cytochrome c oxidase (COX) deficiency [
].
This entry represents Prokaryotic ubiquitin-like protein Pup from Mycobacterium tuberculosis and similar short proteins, of 50-90 residues in length, predominantly found in Actinobacteria. Pup is covalently conjugated to the e-NH2 groups of lysines on several target proteins (pupylation) such as the malonyl CoA acyl carrier protein (FabD) [
]. Pupylation of FabD was shown to result in its recruitment to the mycobacterial proteasome and subsequent degradation analogous to eukaryotic ubiquitin-conjugated proteins. Searches recovered Pup orthologous in all major actinobacteria lineages including the basal bifidobacteria and also sporadically in certain other bacterial lineages [].Members of this protein family, formerly known as DUF797, have a conserved motif with a G [EQ] signature at the C terminus and are suitable for conjugation via the terminal glutamate or the deamidated glutamine (as shown in the case of the Mycobacterium Pup []). Pup is structurally unrelated to the ubiquitin fold and has convergently evolved the function of protein modifier. It has a binding-induced folding recognition mechanism that is different from substrate recognition in the ubiquitin-proteasome system []. This protein, intrinsically disordered, links to target proteins via the ligase PafA, acquiring an ordered assembly to form two helices connected by a linker, positioning the C-terminal glutamate in the active site of this ligase [].
This family consists of several hypothetical bacterial proteins of around 150 residues in length. Members of this family seem to be founds exclusively in the Class Alphaproteobacteria. The function of this family is unknown.
Members of this family are found in several Proteobacteria, including Pseudomonas putida (strain KT2440), Bdellovibrio bacteriovorus HD100 (three members), Aeromonas hydrophila, and Chromobacterium violaceum ATCC 12472. The function is unknown.
Bacillus spp. are Gram-positive aerobic rods that are able to form endo-spores that allow them to survive in almost any environment. The many different species exhibit a wide variation of physiological abilities, their spores being resistant, for example, to heat, cold, disinfection and radiation. However, the spores require oxygen to sporulate, which has important consequences. Of particular interest to researchers are Bacillus anthracis, Bacillus cereus and Bacillus subtilis, all extremely pathogenic microbes that owe their virulence to the exotoxins they secrete and to the extracellular polypeptide and polysaccharide capsules that protect them from the host immune system [].The capsule of B. anthracis is composed of poly-D-glutamic acid, which is the
principal non-toxin virulence factor of the bacterium. It is believed toinhibit host defence via evasion of macrophages, and, in conjunction with
the lethal anthrax and oedema toxin, spreads rapidly through the host []. Three virulence plasmid-associated enzymes are responsible for the synthesis of the capsule, termed CapA, CapB and CapC. The "cap"region is found on the B. anthracis pX02 plasmid, and is transcriptionally regulated by cytoplasmic levels of bicarbonate.
Further analysis of the two major B. anthracis virulence plasmids (pX02 and
pX01) has revealed that transcription and translation of the cap synthesisenzymes in pX02 is essential for activation of pX01, which carries the pag, lef and cya exotoxin genes [
]. It is believed that, together with CapB and CapC, CapA forms a polyglutamyl sythetase complex to produce the mature polyglutamate capsule. In addition, it has been suggested that CapC is the complex's endogenous acceptor of glutamyl residues.
Bacillus spp. are Gram-positive aerobic rods that are able to form endo-
spores that allow them to survive in almost any environment. The manydifferent species exhibit a wide variation of physiological abilities, their
spores being resistant, for example, to heat, cold, disinfection andradiation. However, the spores require oxygen to sporulate, which has
important consequences. Of particular interest to researchers areBacillus anthracis, Bacillus cereus and Bacillus subtilis, all extremely pathogenic microbes that owe their virulence to the exotoxins they secrete and to the extracellular polypeptide and polysaccharide capsules that protect them from the host immune system [
].The capsule of B. anthracis is composed of poly-D-glutamic acid, which is the
principal non-toxin virulence factor of the bacterium []. It is believed to inhibit host defence via evasion of macrophages, and, in conjunction with the lethal anthrax and oedema toxin, spreads rapidly through the host. Three virulence plasmid-associated enzymes are responsible for the synthesis of the capsule, termed CapA, CapB and CapC. The "cap"region is found on the B. anthracis pX02 plasmid, and is transcriptionally regulated by cytoplasmic levels of bicarbonate [
].Further analysis of the two major B. anthracis virulence plasmids (pX02 and
pX01) has revealed that transcription and translation of the cap synthesisenzymes in pX02 is essential for activation of pX01, which carries the pag, gd; lef and cya exotoxin genes [
]. It is believed that, together with CapB and gd; CapC, CapA forms a polyglutamyl sythetase complex to produce the mature polyglutamate capsule. Moreover, the capB gene is the first cistron in the cap region, and regulates the expression of all three capsule synthesis genes.
Members are found in Myxococcus xanthus (six members), Geobacter sulfurreducens, and Pseudomonas aeruginosa; a short protein homologous to the N-terminal region is found in Rhizobium loti (Mesorhizobium loti). All sequence are from Proteobacteria. The function is unknown.
This family consists of several hypothetical archaeal and bacterial proteins of unknown function, including
from Aquifex aeolicus. The structure of this protein has been solved [
] but its function remains unknown. Members of this family seem to have an acyl-CoA N-acyltransferase topology.
RNA polymerase-associated protein RapA is a transcription regulator that activates transcription by stimulating RNA polymerase (RNAP) recycling [
]. This stimulation occurs in cases of stress conditions such as supercoiled DNA or high salt concentrations. The protein probably acts by releasing the RNAP, when it is trapped or immobilized on tightly supercoiled DNA however, it does not activate transcription on linear DNA. RapA is probably not involved in DNA repair. The protein has a higher affinity for the core RNAP than for the holoenzyme and its ATPase activity is stimulated by binding to RNAP. RapA belongs to the SNF2/RAD54 helicase family and contains 1 helicase ATP-binding domain.
