This family includes various protein that are involved in antirestriction. The ArdB protein efficiently inhibits restriction by
members of the three known families of type I systems of Escherichia coli [].
This entry represents FP protein from Orgyia pseudotsugata multicapsid polyhedrosis virus and other sequences from arthropods and baculovirus. The function of the FP protein is not known. The protein is missing in baculovirus FP (Few Polyhedra) mutants [
].
The function of this protein family is unknown. Mutations in protein C (C12orf57) are implicated in the pathogenesis of colobomatous microphthalmia [
,
].
Members of this protein family average about 130 residues in length and include an almost perfectly conserved motif GxxExxY. Members occur in a wide range of prokaryotes, including Proteobacteria, Perrucomicrobia, Cyanobacteria, Bacteriodetes, Archaea, etc. They belong to the PD-(D/E)XK nuclease superfamily [
].
Members of this family are very short (~60 residue) polypeptides, among which the fifth and third to last residues are an invariant Phe and invariant Ser, respectively. Because members occur in a conserved context with a putative peptide-modifying radical SAM/SPASM domain protein, we suggest that members of this family may be the modification target. The gene symbol fxsA reflects both the FXA motif and the proposed role as a ribosomal natural product.
Members of this uncharacterised protein family are found in various Mycobacterium phage genomes, in Streptomyces coelicolor plasmid SCP1, and in bacterial genomes near various markers that suggest lateral gene transfer. Their function is unknown.
This small, uncommon, poorly conserved protein is found primarily in the Firmicutes. It features are pair of CxxC motifs separated by about 20 amino acids, followed by a highly hydrophobic region of about 45 amino acids. It has no conserved gene neighbourhood, and its function is unknown.
Human and mouse LSP1 proteins consist of two domains: an N-terminal acidic domain and a C-terminal basic domain [
,
]. The C-terminal domains are highly conserved and include several putative Ser/Thr phosphorylation sites []. Immunoprecipitation of LSP1 from 32P-orthophosphate-loaded cells indicates that LSP1 is a phosphoprotein []. The N-terminal domain of mouse LSP1 contains two putative Ca2(+)-binding sites, but these are not conserved in human LSP1; nevertheless, a different Ca2(+)-binding site may exist in the human protein, indicating functional rather than strict sequence conservation of the two proteins [,
].Although the precise function of LSP is unclear, it is an F-actin binding protein thought to be involved in transmembrane signal transduction via its postulated calcium-binding function [
] (although evidence for the existence of the calcium-binding sites is weak). The expression pattern of LSP1 is highly restricted. Non-lymphoid cell lines or normal mouse tissues such as brain, lung, liver, skeletal muscle, kidney or testis do not express the protein, and it appears that its expression in the hematopoietic system is restricted to the lymphocyte, macrophage and neutrophil lineages [].
During mitosis, genomic integrity is maintained by the proper coordination of mitotic events through the spindle checkpoint. The bifurcated spindle checkpoint blocks cell-cycle progression at metaphase by monitoring unattached kinetochores, and inhibits mitotic exit in response to the incorrect orientation of the mitotic spindle. Bfa1p is a budding yeast spindle checkpoint regulator in the Bub2p checkpoint pathway for proper mitotic exit. A Bfa1p interacting protein, termed Ibd2p, has been identified in the budding yeast Saccharomyces cerevisiae [
].IBD2 (Inhibition of Bud Division 2) is not an essential gene. However, over-expression of Ibd2p has been shown to induce mitotic arrest, with increased levels of Clb2p in wild type and mad2Delta, but not in deletion mutants of BUB2 and BFA1. Overall, it is thought likely that IBD2 encodes a novel component of the BUB2-dependent spindle checkpoint pathway that functions upstream of BUB2 and BFA1 [
].
The CDK2-associated cyclin A1 is essential for spermatogenesis, and contributes to leukemogenesis, but its detailed molecular functions are unclear. Several novel cyclin A1/CDK2 interaction partners have been identified by means of a yeast triple-hybrid approach, including INCA1, KARCA1 and PROCA1. These proteins link the cyclin A1-CDK2 complex to diverse cellular processes, such as DNA repair, signalling and splicing [].One of the new genes has been cloned and characterised, and named INCA1 (inhibitor of CDK interacting with cyclin A1). The nuclear INCA1 protein is evolutionarily conserved but shares no similarity with any known gene. This novel protein and two other interacting partners serve as substrates for the cyclin A1-CDK2 kinase complex [
].
Primary ciliary dyskinesia (PCD) is an autosomal recessive disease that results from mutations affecting the normal function of cilia. Expression of the DPCD product of the uncharacterised gene dpcd has been shown to increase during ciliated cell differentiation [
]. Nevertheless, an analysis of DPCD mutations in cases of human PCD was not able to confirm any specific disease-causing mutations, although one variant could not be ruled out. DPCD therefore remains a novel candidate gene for PCD [].
The Notch signalling pathway is a conserved intercellular signalling mechanism that is essential for proper embryonic development in numerous metazoan organisms [
]. Members of the Notch gene family encode transmembrane (TM) receptors that are critical for various cell-fate decisions. Multiple ligands that activate Notch and related receptors have been identified, including the Delta and Serrate proteins in Drosophila, and Jagged, the vertebrate orthologue of Serrate [].Members of the Jagged/Serrate group are single-pass TM proteins. They possess a large extracellular region that contains a highly conserved disulphide-rich Delta/Serrate/LAG-2 (DSL) domain, and a variable number of EGF repeats. The cytoplasmic tail region is relatively short (100-150 amino acids) and, following proteolytic cleavage, may translocate to the nucleus to mediate nuclear signalling events [
].Defects in Jagged have been shown to result in Alagille syndrome, an autosomal dominant disorder that results in a paucity of intrahepatic bile ducts [
].This entry represents the Jagged/Serrate protein family.
RseC is thought to be a positive regulator of sigmaE activity [
]. However, an rseC mutant was reported to show wild-type sigmaE activity under inducing conditions or non-inducing conditions []. RseC plays a role in reduction of the SoxR iron-sulphur cluster, along with proteins encoded by the rsxABCDGE operon []. Salmonella typhimurium RseC is involved in thiamine synthesis [].
FRG2, a member of a chromosomally dispersed gene family, has been identified and characterised [
]. Low levels of FRG2 expression were detectable in differentiating myoblasts of autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) patients, partly from chromosome 4, but originating largely from its homologue on chromosome 10 []. In non-FSHD myopathy patients, only distantly-related FRG2 homologues are transcribed, while differentiating myoblasts from healthy controls do not express any member of this gene family []. The localisation of FRG2 genes close to the D4Z4 repeats on chromosomes 4 and 10, their transcriptional up-regulation in FSHD myoblast cultures, potential involvement in myogenesis, and promoter properties, render FRG2 an attractive candidate for FSHD pathogenesis. Nevertheless, sequence- and motif-based searches have shed no light on the function of the predicted protein [].
Little is known about protein Fyv8 (also known as function required for yeast viability protein 8); however, it seems that the Fyv8 gene is needed for survival upon exposure to K1 killer toxin [
]. It also may be involved in the resistance to unfolded protein response (UPR)-inducing agents [].
Keratin-associated proteins (KAPs) are cysteine-rich proteins synthesized during the differentiation of hair matrix cells, and form hair
fibres in association with hair keratin intermediate filaments [,
]. This entry also includes the high-sulfur and high-tyrosine keratins from sheep and goats.In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins, which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins [
]. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.
This entry represents the triphosphoribosyl-dephospho-CoA synthases CitG and MdcB. CitG and MdcB are closely related and produce the same molecule, triphosphoribosyl-dephospho-CoA, which becomes the prosthetic group of acyl carrier protein subunits of citrate lyase and malonate decarboxylase respectively [
,
].
The crystal structure of two of these members shows that this domain has a ferredoxin like fold and is likely to exists as at least homodimers. Sulphate ions are located at the dimer interfaces, which are thought to confer additional stability. Although the function of this domain remains to be identified, its structure suggests a role in protein-protein interactions possibly regulated by the binding of small-molecule ligands [
]. Solution of the structure of the hyperthermophilic anaerobic Thermotoga maritima sequence, (
), shows that this has a beta-α-β-beta-α-β ferredoxin-like fold and assembles as a homotetramer. It was possible to identify a pocket in each monomer that bound an unidentified ligand. It was also found that it bound charged thiamine though not hydroxymethyl pyrimidine. Under oxidative conditions this bacterium is under stress, and the transcriptional unit within which this protein is expressed is up-regulated in these conditions, suggesting that the chelation of cytoplasmic thaimine is part of the response mechanism to such oxidatvie stress, which is mediated by this family [
].
Protein Ocr protects Bacteriophage T7 DNA from degradation and modification by the host restriction-modification complex [
,
]. The structure of Ocr from T7 has shown that this protein mimics the size and shape of a bent DNA molecule, that binds to and completely occupies the DNA-binding sites of all known families of the complex type I DNA restriction enzymes which inhibits the restriction endonuclease activity [,
]. Ocr binds to bacterial RNA polymerase (RNAP) and competes with sigma factors resulting in host transcription inhibition [] and it also inhibits the host exclusion defense system BREX [].
This entry includes Liat1 (ligand of Ate1) from animals. Liat1 interacts with Ate1 and may be involved in Ate1-mediated N-terminal arginylation. Ate1 is a component of the N-end rule pathway, which recognizes and polyubiquitylates proteins containing N-terminal degradation signals, targeting them for degradation by the proteasome.In primates, Liat1 genes are subtelomeric and Liat1 protein contains tandem repeats of a 10-residue sequence, whereas Liat1 proteins of other mammals contain a single copy of this motif [
].
This family consists of the chorion superfamily proteins classes A, B, CA, CB and high-cysteine HCB from silk, gypsy and polyphemus moths. The chorion proteins make up the moths egg shell - a complex extracellular structure [
].
This family contains XisI proteins, also known as FdxN element excision controlling factors, and similar proteins. FdxN element is excised from the chromosome during heterocyst differentiation in cyanobacteria. This is accomplished by the large serine recombinase XisF (fdxN element site-specific recombinase). The xisH as well as the xisF and xisI genes are required. XisI may function as recombination directionality factor (RDF), and needs XisH which may function as an endonuclease [
].
This family contains XisI proteins, also known as FdxN element excision controlling factors, and similar proteins. FdxN element is excised from the chromosome during heterocyst differentiation in cyanobacteria. This is accomplished by the large serine recombinase XisF (fdxN element site-specific recombinase). The xisH as well as the xisF and xisI genes are required. XisI may function as recombination directionality factor (RDF), and needs XisH which may function as an endonuclease [
].
This family includes the Bacillus subtilis YfhJ protein
, which is functionally uncharacterised. This is not a homologue of Escherichia coli YfhJ, a synonym for IscX, which belongs to
. This family of proteins is found in bacteria. Proteins in this family are approximately 90 amino acids in length and contain a highly conserved WVELL motif.
These proteins are functionally uncharacterised. However it has been predicted that these proteins are functionally equivalent to the UmuD subunit of polymerase V from Gram-negative bacteria [
].
The LAZY1 family contains plant-specific proteins involved in gravitropism by regulation of auxin flow [
,
,
,
,
]. The direction of gravity is perceived by plants mainly by gravity-sensing cells (statocytes), which detect the sedimentation of starch-accumulating high-density amyloplasts. This results in a chemical signal that is transmitted to responding tissues (auxin transport), where the signal induces the differential growth of the lower and upper surfaces of gravity-responsive organs.
This entry represents FAM118, including FAM118A and FAM118B.FAM118A has been identified as a gene expressed in glioblastoma stem cells, but not expressed in neural stem cells [
]. Its function is unkown.Cajal bodies are specialized compartments in the nucleus that are involved in the biogenesis of small nuclear ribonucleoproteins (snRNPs). FAM118B is a component of Cajal bodies that plays an important role in Cajal body formation, snRNP biogenesis and cell viability [
].
Protein AMBP is a precursor that gives rise to two different secreted proteins upon endopeptidase cleavage in hepatocytes [
]. One of the two proteins after cleavage, alpha1-microglobulin is a glycoprotein that belongs to the lipocalin family. It has immunoregulatory properties and is involved in heme-catabolism [,
]. The second protein, bikunin, is a Kunitz-type proteinase inhibitor of the inter-alpha-inhibitor family [].
This entry represents uncharacterized proteins from archaea, including protein MJ0935 from
Methanocaldococcus jannaschii . These proteins are related to the eukaryote integral membrane proteins EMC3 and TMCO1-like. The structure has been solved for protein MJ0480 also from
M. jannaschii, which has four transmembrane helices. It has been suggested that archaeal proteins may function as insertases of the archaeal plasma membrane [
].
This entry represents a group of insect proteins, including protein snakeskin (Ssk) from Drosophila melanogaster. It is required for assembly of smooth septate junctions (sSJs), together with mesh and Tsp2A [
,
].
This entry represents a group of plant proteins, including TAP1 from Antirrhinum majus and THNL1/2 from Arabidopsis. THNL1/2 belongs to the plant thionin (PR-13) family and may be involved in plant defense [
].
The YaaC-like protein family includes the Bacillus subtilis YaaC protein
, which is functionally uncharacterised. This family of proteins is found in bacteria.
This family represents a group of fungal proteins, including PriA from Lentinula edodes and CPL1 from Cryptococcus neoformans. PriA was identified as a gene that may play a role during the beginning of fruiting [
,
]. CPL1 is a virulence factor which promotes fungal virulence by enhancing type 2 inflammation in the mouse host[[cite35896747]].
TOPAZ1 is a germ cell specific protein highly conserved in vertebrates [
]. It is essential for male meiotic progression []. TOPAZ1 is an abbreviation for testis and ovary-specific PAZ domain-containing protein 1, although TOPAZ1 does not contain a PAZ domain.
This entry includes IgA-inducing proteins (IGIPs) from animals [
]. Monocyte-derived dendritic cells are the primary producers of human IGIP. IGIP induces expression of IgA in the presence of IL-10 [].
The function of these proteins is not clear. A member of this family from T. thermophilus, TTHA1554, has been shown to bind to glutamine synthetase and cystathionine beta-lyase [
].
Him1 (high induction of mutagenesis protein 1) plays a role in the control of spontaneous and induced mutagenesis [
]. It is thought to participate in the control of processing of mutational intermediates appearing during error-prone bypass of DNA damage. This entry also includes mitochondrial protein Fmp52, whose function is not clear.
Protein CDV3 (carnitine deficiency-associated protein 3) is up-regulated in ventricles of juvenile visceral steatosis mice [
]. Another study showed that CDV3 is phosphorylated by Abl, a tyrosine kinase involved in normal B cell development [].
Budding yeast Red1 is involved in meiotic recombination and chromosome segregation during homologous chromosome formation. Red1 is a component of the axial element protein cores in synaptonemal complexes (SC). Synaptonemal complexes are found at synapses between homologous chromosomes during meiosis, and form when sister chromatids condense upon axial elements [
]. Besides its structural role in SC, Red1 also couples checkpoint signalling to SC formation []. This entry also includes fission yeast Rec10, which is involved primarily in the early steps of meiotic recombination localised to chromosome III [
].Members of this family are homologues of SCYP2-3 from vertebrates and ASY3-4 from plants [
].
PrpF is a protein found in the 2-methylcitrate pathway. It is structurally similar to DAP epimerase and proline racemase. This protein is an aconitate- isomerise converting trans-aconitate to cis-aconitate [
,
].
Wnt proteins constitute a large family of secreted molecules that are involved in intercellular signalling during development. The name derives from the first 2 members of the family to be discovered: int-1 (mouse) and wingless (Drosophila) [
]. It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals []. Wnt signalling has been implicated in tumourigenesis, early mesodermal patterning of the embryo, morphogenesis of the brain and kidneys, regulation of mammary gland proliferation and Alzheimer's disease [,
].Wnt-mediated signalling is believed to proceed initially through binding to cell surface receptors of the frizzled family; the signal is subsequently transduced through several cytoplasmic components to B-catenin, which enters the nucleus and activates the transcription of several genes important in
development []. Several non-canonical Wnt signalling pathways have also been elucidated that act independently of B-catenin. Canonical and noncanonical Wnt signaling branches are highly interconnected, and cross-regulate each other [].Members of the Wnt gene family are defined by their sequence similarity to mouse Wnt-1 and Wingless in Drosophila. They encode proteins of ~350-400 residues in length, with orthologues identified in several, mostly vertebrate, species. Very little is known about the structure of
Wnts as they are notoriously insoluble, but they share the following features characteristics of secretory proteins: a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines [] that are probably involved in disulphide bonds. The Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters. Fifteen major Wnt gene families have been identified in vertebrates, with multiple subtypes within some classes.The Wnt-1 gene was first identified in 1982 as a proto-oncogene activated by
the integration of mouse mammary tumour virus (MMTV) in mammary tumours.With the identification of Drosophila wingless, however, it became clear
that Wnt genes are important regulators of many developmental decisions.Mutation of the embryonic mouse Wnt-1 gene leads to loss of the midbrain and
cerebellum; and a number of processes including segment polarity and limbdevelopment are interrupted in Drosophila wingless mutants [
].
Wnt proteins constitute a large family of secreted molecules that are involved in intercellular signalling during development. The name derives from the first 2 members of the family to be discovered: int-1 (mouse) and wingless (Drosophila) [
]. It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals []. Wnt signalling has been implicated in tumourigenesis, early mesodermal patterning of the embryo, morphogenesis of the brain and kidneys, regulation of mammary gland proliferation and Alzheimer's disease [,
].Wnt-mediated signalling is believed to proceed initially through binding to cell surface receptors of the frizzled family; the signal is subsequently transduced through several cytoplasmic components to B-catenin, which enters the nucleus and activates the transcription of several genes important in
development []. Several non-canonical Wnt signalling pathways have also been elucidated that act independently of B-catenin. Canonical and noncanonical Wnt signaling branches are highly interconnected, and cross-regulate each other [].Members of the Wnt gene family are defined by their sequence similarity to mouse Wnt-1 and Wingless in Drosophila. They encode proteins of ~350-400 residues in length, with orthologues identified in several, mostly vertebrate, species. Very little is known about the structure of
Wnts as they are notoriously insoluble, but they share the following features characteristics of secretory proteins: a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines [] that are probably involved in disulphide bonds. The Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters. Fifteen major Wnt gene families have been identified in vertebrates, with multiple subtypes within some classes.The Wnt-2 gene was isolated from a human lung cDNA library in 1988 [
]. The protein was initially named IRP for Int-1 Related Protein and later termed
Wnt-2. Northern blot analysis from a range of embryonic and adult tissues revealed that the gene was expressed almost exclusively in placenta and lung.
Mutation of the mouse Wnt-2 gene leads to placental defects.
Wnt proteins constitute a large family of secreted molecules that are involved in intercellular signalling during development. The name derives from the first 2 members of the family to be discovered: int-1 (mouse) and wingless (Drosophila) []. It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals []. Wnt signalling has been implicated in tumourigenesis, early mesodermal patterning of the embryo, morphogenesis of the brain and kidneys, regulation of mammary gland proliferation and Alzheimer's disease [,
].Wnt-mediated signalling is believed to proceed initially through binding to cell surface receptors of the frizzled family; the signal is subsequently transduced through several cytoplasmic components to B-catenin, which enters the nucleus and activates the transcription of several genes important in
development []. Several non-canonical Wnt signalling pathways have also been elucidated that act independently of B-catenin. Canonical and noncanonical Wnt signaling branches are highly interconnected, and cross-regulate each other [].Members of the Wnt gene family are defined by their sequence similarity to mouse Wnt-1 and Wingless in Drosophila. They encode proteins of ~350-400 residues in length, with orthologues identified in several, mostly vertebrate, species. Very little is known about the structure of
Wnts as they are notoriously insoluble, but they share the following features characteristics of secretory proteins: a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines [] that are probably involved in disulphide bonds. The Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters. Fifteen major Wnt gene families have been identified in vertebrates, with multiple subtypes within some classes.The Wnt-3 gene was first identified in mouse in 1987, where it was found to
be expressed during embryogenesis and in adult brain. Insertion of proviralDNA from mouse mammary tumour virus (MMTV) occurs at the mouse Wnt-3 locus,
leading to activation of the gene []. However, the human Wnt-3 gene was notfound to be amplified or rearranged in breast cancer tissues [
].
Wnt proteins constitute a large family of secreted molecules that are involved in intercellular signalling during development. The name derives from the first 2 members of the family to be discovered: int-1 (mouse) and wingless (Drosophila) []. It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals []. Wnt signalling has been implicated in tumourigenesis, early mesodermal patterning of the embryo, morphogenesis of the brain and kidneys, regulation of mammary gland proliferation and Alzheimer's disease [,
].Wnt-mediated signalling is believed to proceed initially through binding to cell surface receptors of the frizzled family; the signal is subsequently transduced through several cytoplasmic components to B-catenin, which enters the nucleus and activates the transcription of several genes important in
development []. Several non-canonical Wnt signalling pathways have also been elucidated that act independently of B-catenin. Canonical and noncanonical Wnt signaling branches are highly interconnected, and cross-regulate each other [].Members of the Wnt gene family are defined by their sequence similarity to mouse Wnt-1 and Wingless in Drosophila. They encode proteins of ~350-400 residues in length, with orthologues identified in several, mostly vertebrate, species. Very little is known about the structure of
Wnts as they are notoriously insoluble, but they share the following features characteristics of secretory proteins: a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines [] that are probably involved in disulphide bonds. The Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters. Fifteen major Wnt gene families have been identified in vertebrates, with multiple subtypes within some classes.Wnt-4 cDNA was isolated from mouse using a PCR-based strategy, where it was
found to be expressed in adult tissues, particularly in brain and lung [].Wnt-4 is believed to act downstream of progesterone signalling to play
an important role in mammary gland development. Furthermore, mutationsin the Wnt-4 gene have been linked to kidney defects [
].
Wnt proteins constitute a large family of secreted molecules that are involved in intercellular signalling during development. The name derives from the first 2 members of the family to be discovered: int-1 (mouse) and wingless (Drosophila) [
]. It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals []. Wnt signalling has been implicated in tumourigenesis, early mesodermal patterning of the embryo, morphogenesis of the brain and kidneys, regulation of mammary gland proliferation and Alzheimer's disease [
,
].Wnt-mediated signalling is believed to proceed initially through binding to cell surface receptors of the frizzled family; the signal is subsequently transduced through several cytoplasmic components to B-catenin, which enters the nucleus and activates the transcription of several genes important in
development []. Several non-canonical Wnt signalling pathways have also been elucidated that act independently of B-catenin. Canonical and noncanonical Wnt signaling branches are highly interconnected, and cross-regulate each other [].Members of the Wnt gene family are defined by their sequence similarity to mouse Wnt-1 and Wingless in Drosophila. They encode proteins of ~350-400 residues in length, with orthologues identified in several, mostly vertebrate, species. Very little is known about the structure of
Wnts as they are notoriously insoluble, but they share the following features characteristics of secretory proteins: a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines [] that are probably involved in disulphide bonds. The Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters. Fifteen major Wnt gene families have been identified in vertebrates, with multiple subtypes within some classes.Wnt-6 cDNA was isolated from mouse using a PCR-based strategy, where it
was found to be expressed in adult tissues, particularly in brain and lung[
]. Furthermore, Wnt-6 is expressed in the ureter bud, where it is believedto activate kidney tubule development [
].
RNA-binding protein E3 from Vaccinia virus (E3L) is a dsRNA-binding protein capable of inhibiting protein kinase R and is an effective IRF3 and -7 phosphorylation inhibitor [
]. The C terminus of E3L binds to double-stranded RNA (dsRNA), while the N terminus of E3L is required for the additional regulation of eIF2alpha phosphorylation [].Protein E3 from Variola virus is also included in this family. It plays a role in the inhibition of multiple cellular antiviral responses activated by dsRNA, such as inhibition of PKR activation, apoptosis, and IFN-mediated antiviral activities [
].
S100A6 is a member of the S100 domain family within the EF-hand Ca
2+-binding proteins superfamily. Note that the S-100 hierarchy, to which this S-100A6 group belongs, contains only S-100 EF-hand domains, other EF-hands have been modeled separately [
]. S100 proteins exhibit unique patterns of tissue- and cell type-specific expression and have been implicated in the Ca2+-dependent regulation of diverse physiological processes, including cell cycle regulation, differentiation, growth, and metabolic control [
,
,
,
]. S100A6 is normally expressed in the G1 phase of the cell cycle in neuronal cells. The function of S100A6 remains unclear, but evidence suggests that it is involved in cell cycle regulation and exocytosis. S100A6 may also be involved in tumorigenesis; the protein is overexpressed in several tumours. Ca
2+binding to S100A6 leads to a conformational change in the protein, which exposes a hydrophobic surface for interaction with target proteins. Several such proteins have been identified: glyceraldehyde-3-phosphate dehydrogenase, annexins 2, 6 and 11 and Calcyclin-Binding Protein (CacyBP) [
,
].
This domain family is found in eukaryotes, and is approximately 30 amino acids in length. The family is found in association with
. This family is a homeobox protein involved in differentiation of embryonic cells to form the abdominal region.
Proteins in this family are related to EcsC from Bacillus subtilis. This protein is found in an operon with EcsA and EcsB which are components of an ABC transport system [
]. The function of this protein is unknown.
Prion protein (PrP-c) [
,
,
] is a small glycoprotein found in high quantity in the brain of animals infected with certain degenerative neurological diseases, such as sheep scrapie and bovine spongiform encephalopathy (BSE), and the human dementias Creutzfeldt-Jacob disease (CJD) and Gerstmann-Straussler syndrome (GSS). PrP-c is encoded in the host genome and is expressed both in normal and infected cells. During infection, however, the PrP-c molecule become altered (conformationally rather than at the amino acid level) to an abnormal isoform, PrP-sc. In detergent-treated brain extracts from infected individuals, fibrils composed of polymers of PrP-sc, namely scrapie-associated fibrils or prion rods, can be evidenced by electron microscopy. The precise function of the normal PrP isoform in healthy individuals remains unknown. Several results, mainly obtained in transgenic animals, indicate that PrP-c might play a role in long-term potentiation, in sleep physiology, in oxidative burst compensation (PrP can fix four Cu2+ through its octarepeat domain), in interactions with the extracellular matrix (PrP-c can bind to the precursor of the laminin receptor, LRP), in apoptosis and in signal transduction (costimulation of PrP-c induces a modulation of Fyn kinase phosphorylation) [].The normal isoform, PrP-c, is anchored at the cell membrane, in rafts, through a glycosyl phosphatidyl inositol (GPI); its half-life at the cell surface is 5 h, after which the protein is internalised through a caveolae-dependent mechanism and degraded in the endolysosome compartment. Conversion between PrP-c and PrP-sc occurs likely during the internalisation process. In humans, PrP is a 253 amino acid protein, which has a molecular weight of 35-36kDa. It has two hexapeptides and repeated octapeptides at the N terminus, a disulphide bond and is associated at the C terminus with a GPI, which enables it to anchor to the external part of the cell membrane. The secondary structure of PrP-c is mainly composed of α-helices, whereas PrP-sc is mainly β-sheets: transconformation of α-helices into β-sheets has been proposed as the structural basis by which PrP acquires pathogenicity in TSEs. The three-dimensional structures shows the protein to be made of a globular domain which includes three α-helices and two small antiparallel β-sheet structures, and a long flexible tail whose conformation depends on the biophysical parameters of the environment. Crystals of the globular domain of PrP have recently been obtained; their analysis suggests a possible dimerisation of the protein through the three-dimensional swapping of the C-terminal helix 3 and rearrangement of the disulphide bond.
Replication proteins (rep) are involved in plasmid replication. The Rep protein binds to the plasmid
DNA and nicks it at the double strand origin (dso) of replication. The 3'-hydroxyl end created is extended by the host DNA replicase, and the 5' end is displaced during synthesis. At the end of one
replication round, Rep introduces a second single stranded break at the dso and ligates the ssDNAextremities generating one double-stranded plasmid and one circular ssDNA form. Complementary strand
synthesis of the circular ssDNA is usually initiated at the single-stranded origin by the host RNApolymerase [
].
During F plasmid conjugation, the SOS response is suppressed by PsiB, an F-plasmid-encoded protein that binds and sequesters free RecA to prevent filament formation. PsiB contains a central five-stranded anti-parallel beta sheet that is buttressed by alpha helices from the N and C termini. Its structure is similar to CapZ, a eukaryotic actin filament capping protein [
].
Wnt proteins constitute a large family of secreted molecules that are involved in intercellular signalling during development. The name derives from the first 2 members of the family to be discovered: int-1 (mouse) and wingless (Drosophila) [
]. It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals []. Wnt signalling has been implicated in tumourigenesis, early mesodermal patterning of the embryo, morphogenesis of the brain and kidneys, regulation of mammary gland proliferation and Alzheimer's disease [,
].Wnt-mediated signalling is believed to proceed initially through binding to cell surface receptors of the frizzled family; the signal is subsequently transduced through several cytoplasmic components to B-catenin, which enters the nucleus and activates the transcription of several genes important in
development []. Several non-canonical Wnt signalling pathways have also been elucidated that act independently of B-catenin. Canonical and noncanonical Wnt signaling branches are highly interconnected, and cross-regulate each other [].Members of the Wnt gene family are defined by their sequence similarity to mouse Wnt-1 and Wingless in Drosophila. They encode proteins of ~350-400 residues in length, with orthologues identified in several, mostly vertebrate, species. Very little is known about the structure of
Wnts as they are notoriously insoluble, but they share the following features characteristics of secretory proteins: a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines [] that are probably involved in disulphide bonds. The Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters. Fifteen major Wnt gene families have been identified in vertebrates, with multiple subtypes within some classes.This entry represents proteins Wnt-8A, Wnt-8C and similar sequences from vertebrates.
VEG protein is highly conserved among Gram-positive bacteria. It stimulates biofilm formation through inducing transcription of the tapA-sipW-tasA operon. The products of this operon are responsible for production of the amyloid fibre (TasA) component of the biofilm. Veg or a Veg-induced protein acts as an antirepressor of SinR - part of the major overall biofilm transcriptional control system - to regulate and stimulate biofilm formation. Veg is transcribed at high levels during both exponential growth and sporulation [
,
].
This family represents protein spackle from Bacteriophage T4, which inhibits viral DNA ejection into the host cytoplasm, thereby conferring the infected host bacteria with immunity against secondary phage infection [
]. It localizes to the periplasm and inhibits the activity of tail-associated lysozyme, thereby preventing penetration by the tail tube of incoming phages [,
]. It interacts with the baseplate central spike protein gp5, therefore, spackle selectively inhibits the lysozyme activity of gp5, but not that of T4 lysozyme.
This family includes poorly characterised bacterial proteins, such as YciF from Escherichia coli. This protein is produced by bacteria in response to stress conditions. It adopts a dimeric configuration in which each monomer shows five α-helices. Its function is still unknown [
].
VANGL proteins play important roles in the establishment of planar cell polarity (PCP) [
]. Vangl2 is required for retinal axon guidance [], kidney-branching morphogenesis and glomerular maturation []. It also plays a role in the orientation of stereociliary bundles in the cochlea and is required for polarization and movement of myocardializing cells in the outflow tract and seems to act via RHOA signaling to regulate this process []. It is required for cell surface localization of FZD3 and FZD6 in the inner ear [].
Protein wntless (Wls) regulates Wnt proteins sorting and secretion in a feedback regulatory mechanism [
,
,
]. This reciprocal interaction plays a key role in the regulation of expression, subcellular location, binding and organelle-specific association of Wnt proteins. It also plays also an important role in establishment of the anterior-posterior body axis formation during development [].
Several peroxisome biogenesis factors, termed peroxins (PEXs), are involved in the transport of peroxisomal proteins from the cytosol to peroxisomes. ABERRANT PEROXISOME MORPHOLOGY9 (APEM9) is involved in peroxisomal protein transport through its recruitment of the AAA ATPase complex PEX1-PEX6 to peroxisomal membranes via protein-protein interactions with PEX6 [
]. APEM9 has a similar function in plants to mammalian Pex26 and yeast Pex15p, although the amino acid conservation among them is very low. APEM9 plays critical roles in peroxisome biogenesis and function, which is essential for jasmonic acid production and pollen maturation and germination [].
This entry represents Protein YfgG from Escherichia coli (strain K12) and similar proteins from Gammaproteobacteria. YfgG may be related to the resistance to the iron analogue gallium nitrate (Ga(NO3)3), and to the tolerance to nickel and cobalt stress [
,
]. However, the exact function is still unknown.
The representative of this plant family is PAIR1 (HOMOLOGOUS PAIRING ABERRATION IN RICE MEIOSIS1), a protein that plays an essential role in establishment of homologous chromosome pairing in meiosis. Mutations in the gene encoding this protein also affect spindle formation and sporulation [
]. This family also contains the Putative recombination initiation defects 3 (AtPRD3) involved in the meiotic recombination initiation [].In flowering plants, gametophyte formation relies on meiosis. In meiosis I, the homologous chromosomes are separated into two daughter cells. In meiosis II, the sister chromosomes are then separated into newly formed daughter cells. During prophase I, several events occurs: sister chromatid cohesion, homologous chromosome synapsis, recombination, crossover formation and chromosome segregation. Homologous recombination is initiated from the formation of DNA double-strand breaks (DSBs). The formation of DSBs is catalyzed by Spo11 and its homologues. So far, six Arabidopsis proteins, AtSPO11-1, AtSPO11-2, AtPRD1, AtPRD2, AtPRD3 and AtDFO, have been shown to be involved in DSB formation [].
This entry represents bacterial Erp proteins that seem to be specific to Borrelia burgdorferi (a causative agent of Lyme disease). Borrelia Erp proteins are particularly heterogeneous, which might enable them to interact with a wide variety of host components [
].
This entry represents Frg1 (FSHD region gene 1), a protein that is considered to be a candidate for facioscapulohumeral muscular dystrophy (FSHD). FSHD is a dominant neuromuscular disorder caused by deletions in a number of tandem repeat units (called D4Z4) located on chromosome 4q35. D4Z4 contains a transcriptional silencer whose deletion causes the over-expression in skeletal muscle of 4q35 genes, including Frg1 [
,
]. Frg1 is localised to nucleoli and appears to be a component of the human spliceosome []. When overexpressed, it binds and interferes with the activity of the histone methyltransferase Suv4-20h1 both in mammals and Drosophila, inhibiting myogenesis as a result [].
PSY1 is a tyrosine-sulfated peptide isolated from Arabidopsis which promotes cellular proliferation and expansion [
]. Another two tyrosine-sulfated proteins compose this family: PSY2 and PSY3. Their function is not known.
This entry represents eIF4E-associated protein (Eap1) from yeast, which plays a role in cell growth and is implicated in the TOR signaling cascade. Eap1 binds to eIF4E and regulates translation. It competes with eIF4G (the large subunit of the cap-binding complex, eukaryotic initiation factor 4F (eIF4F)) for binding to eIF4E and accelerates mRNA degradation by promoting decapping [
,
,
,
]. It associates with Puf5p and Dhh1p, being essential for Puf5p mediated repression []. This family also includes the uncharacterised protein from S. pombe SPCC14G10.04 () which has been shown to interact with eIF4E, 4F complex subunits [
].
Protein DEK is an abundant and ubiquitous chromatin protein in multicellular organisms (not in yeast) [
,
]. It preferentially binds to superhelical and cruciform DNA, and induces positive supercoils into closed circular DNA []. This protein has two DNA binding domains, the SAP/SAF box located at the centre of the protein, and the second one at the C-terminal, which contains several phosphorylation sites important for its activity. It is involved in cell proliferation, differentiation, senescence and apoptosis, being associated with cancers and autoimmune diseases and a possible therapeutic drug target []. In humans DEK can be secreted by macrophages, and the secreted DEK regulates the proliferation of hematopoietic stem cells and hematopoietic progenitor cells through CXCR2 signaling [].
This entry represents a group of plant proteins, including protein BLISTER (BLI) from Arabidopsis thaliana. BLI interacts with the Pc-G histone methyltransferase CURLY LEAF (CLF) and may also act independently in Arabidopsis development [
]. It negatively controls the activity of IRE1A/IRE1B under normal growth condition [].
Protein Ac34 from Autographa californica nuclear polyhedrosis virus (AcMNPV) induces translocation subunits of the actin nucleator actin-related protein complex Arp2/3 to the nucleus during AcMNPV infection. The Arp2/3 complex regulates actin polymerization and plays a variety of roles during infection, including nuclear actin polymerization to assist in virus replication [
].
This family of proteins is known as FAM76 and it is functionally uncharacterised. It is found in eukaryotes. Proteins in this family are typically between 233 and 341 amino acids in length.
YopX is a protein of plasmid origin found in bacteria. It is of approx. 135 residues and is largely helical, with three identical chains probably complexing into a twelve-chain structure. Yop proteins are a subset of pathogenicity factors known as (Yersinia) outer proteins - Yops - which act as chaperones for other proteins such as X. They are exported by the type III secretion system (TTSS) upon bacterial infection of host cells. The TTSS is encoded on a virulence plasmid and is necessary for the survival and replication of the bacterium within host lymphoid tissues [
].
This protein of 129 residues is expressed in bacteria. It consists of three identical chains of five alpha helices. Two copies of each chain associate into a complex of six units of possible biological significance but of unknown function.
This family consists of several animal EURL proteins. EURL is preferentially expressed in chick retinal precursor cells as well as in the anterior epithelial cells of the lens at early stages of development. EURL transcripts are found primarily in the peripheral dorsal retina, i.e., the most undifferentiated part of the dorsal retina. EURL transcripts are also detected in the lens at stage 18 and remain abundant in the proliferating epithelial cells of the lens until at least day 11. The distribution pattern of EURL in the developing retina and lens suggest a role before the events leading to cell determination and differentiation [
].
Antifungal proteinσ consists of five antiparallel β-strands which are highly twisted creating a β-barrel stabilised by four internal disulphide bridges [
]. A cationic site adjacent to a hydrophobic stretch on the protein surface may constitute a phospholipid binding site []. Members of this entry act as inhibitors of growth of human pathogenic molds and yeasts such as PafB [,
] and opdH [].
NDNF (neuron-derived neurotrophic factor) is a glycosylated, disulfide-bonded secretory protein that contains fibronectin type III domains and two predicted N-linked glycosylation sites [
,
]. It is expressed in brain and spinal cord that promotes migration and neurite growth. It acts as a modulator that promotes endothelial cell survival, vessel formation and plays an important role in the process of revascularization through NOS3-dependent mechanisms [].
This entry represents a group of plant proteins, including protein SWEETIE from Arabidopsis. SWEETIE may be involved in the general control of sugar flux and modulates many important processes such as morphogenesis, flowering, stress responses and senescence [
,
].
This family of proteins is related to the Rhomboid proteins and, thus, is likely to be an intramembrane protein. Proteins in this family are found primarily in actinobacteria.
Capsid protein (CA1, also known as VP1) self-assembles to form the virion icosahedral capsid with a T=1 symmetry. This very small capsid (25 nm in diameter) allows the virus to be very stable in the environment and resistant to some disinfectants, including detergents. It is essential for the initial attachment to host receptors. After attachment, the virus is endocytosed and traffics to the nucleus. The capsid protein binds and transports the viral genome and Rep across the nuclear envelope [
].
This entry represents a group of plant proteins, including TRM32 from Arabidopsis. TRM32 (TON1-RECRUITING MOTIF protein 32) shares the conserved sequence motifs with other TRM proteins. Its function is not clear [].
TONSOKU (also known as MGOUN3 or BRUSHY1 (BRU1)) is a nuclear leucine-glycine-asparagine (LGN) domain protein that links responses to DNA damage and epigenetic gene silencing in Arabidopsis. Mutants with defects in TONSOKU display a fasciated stem and disorganized meristem structures [
]. TONSOKU is specifically expressed during S phase and acts with GIP1 synergistically for the maintenance of centromeric cohesion [].
The precise function of these proteins is unclear, but some of them are involved in flagella motor switch [
]. The region represented in this entry is found in the CheC, CheX, CheA and FliY proteins. In some cases, this region is repeated in multiple copies.
This entry represents a group of plant tetratricopeptide repeat proteins, including PHOX1-4 from Arabidopsis and HIP from Zea mays. They are putative co-chaperones of Hsp90/Hsp70 [
]. PHOX2, also known as CLMP1, is required for plastid separation [].
This entry includes protein Sgt1 (Suppressor of G2 allele of SKP1) and its homologues. In budding yeasts, Sgt1 is required for both SCF (Skp1p/Cdc53p-Cullin-F-box)-mediated ubiquitination, cyclic AMP pathway activity and kinetochore function [
]. Its Schizosaccharomyces pombe homologue, Git7, is required for glucose and cyclic AMP signaling, cell wall integrity, and septation []. Its two homologues in Arabidopsis, SGT1a and SGT1b, can complement two yeast temperature-sensitive sgt1 mutant alleles, suggesting that fundamental cellular function(s) of yeast SGT1in SCF-mediated protein ubiquitylation. Moreover, SGT1a and SGT1b can act as cochaperones with HSP90 and HSC70 and function in regulating multiple resistance (R) genes and environmental responses [,
,
,
].
This entry includes WUSCHEL and homeodomain WUSCHEL-RELATED (WOX) proteins from plants. Proteins in this entry have been classified as a WOX clade that contains the WUS, WOX1, WOX2, WOX3, WOX5, WOX6 and WOX7. WUSCHEL is a transcription factor that plays a central role during early embryogenesis, oogenesis and flowering [
,
]. WOXs are transcription factors that regulate meristem development in embryos, as well as vegetative and reproductive organs [].
