Brefeldin is a lactone antibiotic produced by fungi such as Eupenicillum brefeldianum. It both inhibits protein transport between the endoplasmic reticulum (ER) and the Golgi apparatus, and induces retrograde transport from the Golgi to the ER, leading to protein accumulation within the ER. Screening of a deletion-strain collection for mutants sensitive or resistant to drugs that affect intracellular transport has revealed a number of mutants sensitive to brefeldin A: e.g., deletion of the BRE4 gene was shown to result in brefeldin A-sensitivity [
]. The BRE4 gene product is predicted to contain 10 transmembrane (TM) domains, suggesting that it is likely to be an integral membrane protein, potentially involved in intracellular vesicle transport [].
This entry includes the transforming protein Qin from Avian sarcoma virus, which is homologue of the chicken orthologue of FOXG1, c-qin [
]. It carries transforming activity of the virus. The FOXG subfamily includes a winged helix transcription factor FOXG1, which is also called brain factor 1 (BF-1), brain factor 2 (BF-2), Forkhead box protein G1A, Forkhead box protein G1B, Forkhead box protein G1C, Forkhead-related protein FKHL1, Forkhead-related protein FKHL2, or Forkhead-related protein FKHL3. FOXG1 acts as a transcription repression factor which plays an important role in the establishment of the regional subdivision of the developing brain and in the development of the telencephalon. It is repetitively used in the sequential events of telencephalic development to control multi-steps of brain circuit formation ranging from cell cycle control to neuronal differentiation in a clade- and species-specific manner [
]. Individuals with mutations in FOXG1 harbour "FOXG1-related encephalopathy", characterised by two clinical phenotypes/syndromes including microcephaly, developmental delay, severe cognitive disabilities, early-onset dyskinesia and hyperkinetic movements, stereotypies, epilepsy, and cerebral malformation for those with deletions or intragenic mutations of FOXG1 [
,
,
]. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].The small subunit ribosomal proteins can be categorised as: primary binding proteins, which bind directly and independently to 16S rRNA; secondary binding proteins, which display no specific affinity for 16S rRNA, but its assembly is contingent upon the presence of one or more primary binding proteins; and tertiary binding proteins, which require the presence of one or more secondary binding proteins and sometimes other tertiary binding proteins. The small ribosomal subunit protein S19 contains 88-144 amino acid residues. In Escherichia coli, S19 is known to form a complex with S13 that binds strongly to 16S ribosomal RNA. Experimental evidence [
] has revealed that S19 is moderately exposed on the ribosomal surface, and is designated a secondary rRNA binding protein. S19 belongs to a family of ribosomal proteins [,
] that includes: eubacterial S19; algal and plant chloroplast S19; cyanelle S19; archaebacterial S19; plant mitochondrial S19; and eukaryotic S15 ('rig' protein).
The signatures in this entry match the structural unit of the ribosomal S19 family.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].Ribosomal protein L11 is one of the proteins from the large ribosomal subunit. In Escherichia coli, L11 is known to bind directly to the 23S rRNA and plays a significant role during initiation, elongation, and termination of protein synthesis. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities [
], groups bacteria, plant chloroplast, red algal chloroplast, cyanelle and archaeabacterial L11; and mammalian, plant and yeast L12 (YL15). L11 is a protein of 140 to 165 amino-acid residues. L11 consists of a 23S rRNA binding C-terminal domain and an N-terminal domain that directly contacts protein synthesis factors. These two domains are joined by a flexible linker that allows inter-domain movement during protein synthesis. While the C-terminal domain of L11 binds RNA tightly, the N-terminal domain makes only limited contacts with RNA and is proposed to function as a switch that reversibly associates with an adjacent region of RNA [,
,
,
]. In E. coli, the C-terminal half of L11 has been shown [] to be in an extended and loosely folded conformation and is likely to be buried within the ribosomal structure.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [,
].Ribosomal protein L11 is one of the proteins from the large ribosomal subunit. In Escherichia coli, L11 is known to bind directly to the 23S rRNA and plays a significant role during initiation, elongation, and termination of protein synthesis. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities [
], groups bacteria, plant chloroplast, red algal chloroplast, cyanelle and archaeabacterial L11; and mammalian, plant and yeast L12 (YL15). L11 is a protein of 140 to 165 amino-acid residues. L11 consists of a 23S rRNA binding C-terminal domain and an N-terminal domain that directly contacts protein synthesis factors. These two domains are joined by a flexible linker that allows inter-domain movement during protein synthesis. While the C-terminal domain of L11 binds RNA tightly, the N-terminal domain makes only limited contacts with RNA and is proposed to function as a switch that reversibly associates with an adjacent region of RNA [,
,
,
]. In E. coli, the C-terminal half of L11 has been shown [] to be in an extended and loosely folded conformation and is likely to be buried within the ribosomal structure.This entry represents the C-terminal domain of L11/L12. The domain consists of a three-helical bundle and a short parallel two-stranded β-ribbon, with an overall α3-β4-α4-α5-β5 topology. All five secondary structure elements contribute to a conserved hydrophobic core. The domain is characterised by two extended loops that are disordered in the absence of the RNA but have defined structures in the complex [].
Members of this family have been called SAND proteins [
] although these proteins do not contain a SAND domain. In Saccharomyces cerevisiae, Mon1 is part of the Mon1-Ccz1 complex that acts as the guanine nucleotide exchange factor (GEF) of the yeast Rab7 GTPase Ypt7 [,
]. The Mon1/Ccz1 complex is conserved in eukaryotic evolution and members of this family (previously known as DUF254) are distant homologues to domains of known structure that assemble into cargo vesicle adapter (AP) complexes [,
].
This group represents the riboflavin biosynthesis protein RibBA which has both GTP cyclohydrolase II and 3,4-dihydroxy-2-butanone 4-phosphate synthase activities [
].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].Ribosomal protein L13 is one of the proteins from the large ribosomal subunit
[]. In Escherichia coli, L13 is known to be one of the early assembly proteins of the 50S ribosomal subunit. This entry represents ribosomal protein L13 from bacteria, mitochondria and chloroplasts.
This entry represents the DNA double-strand break repair and V(D)J recombination protein XRCC4, which is found in certain Metazoans, fungi and plants. XRCC4 binds to DNA, and to DNA ligase IV (LIG4) to form the LIG4-XRCC4 complex [
]. The LIG4-XRCC4 complex is responsible for the ligation step in the non-homologous end joining (NHEJ) pathway of DNA double-strand break repair. XRCC4 enhances the joining activity of LIG4. It is thought that XRCC4 and LIG4 are essential for alignment-based gap filling, as well as for final ligation of the breaks []. Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends.
This entry includes glioma tumour suppressor candidate region gene 2 protein (GSCR2) from humans and ribosome biogenesis protein Nop53 from budding yeasts. GSCR2 bears similarity to the glioma tumour suppressor candidate region gene 2 protein (p60) [
]. Nop53 is a nucleolar protein that is involved in biogenesis of the 60S subunit of the ribosome []. It interacts with Nop17 and Nip7 and is required for pre-rRNA processing in Saccharomyces cerevisiae [].
S1FA is an unusual small plant peptide of only 70 amino acids with a basic
domain which contains a nuclear localization signal and a putative DNA binding helix. S1FA is highly conservedbetween dicotyledonous and monocotyledonous plants and may be a DNA-binding protein that specifically recognises the negative promoter element S1F [
].
Protein prenylation is the posttranslational attachment of either a farnesyl group or a geranylgeranyl group via a thioether linkage (-C-S-C-) to a cysteine at or near the carboxyl terminus of the protein. Farnesyl and geranylgeranyl groups are polyisoprenes, unsaturated hydrocarbons with a multiple of five carbons; the chain is 15 carbons long in the farnesyl moiety and 20 carbons long in the geranylgeranyl moiety. There are three different protein prenyltransferases in humans: farnesyltransferase (FT) and geranylgeranyltransferase 1 (GGT1) share the same motif (the CaaX box) around the cysteine in their substrates, and are thus called CaaX prenyltransferases, whereas geranylgeranyltransferase 2 (GGT2, also called Rab geranylgeranyltransferase) recognises a different motif and is thus called a non-CaaX prenyltransferase. Protein prenyltransferases are currently known only in eukaryotes, but they are widespread, being found in vertebrates, insects, nematodes, plants, fungi and protozoa, including several parasites. Each protein consists of two subunits, alpha and beta; the alpha subunit of FT and GGT1 is encoded by the same gene, FNTA. The alpha subunit is thought to participate in a stable complex with the isoprenyl substrate; the beta subunit binds the peptide substrate. In the alpha subunits of both types of protein prenyltransferases, seven tetratricopeptide repeats are formed by pairs of helices that are stabilised by conserved intercalating residues. The alpha subunits of GGT2 in mammals and plants also have an immunoglobulin-like domain between the fifth and sixth tetratricopeptide repeat, as well as leucine-rich repeats at the carboxyl terminus. The functions of these additional domains in GGT2 are as yet undefined, but they are apparently not directly involved in the interaction with substrates and Rab escort proteins. The tetratricopeptide repeats of the alpha subunit form a right-handed superhelix, which embraces the (α-α)6 barrel of the beta subunit [
].
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Rxt3 is a component of the Rpd3L histone deacetylase complex that is responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) [
].
This entry rerpesnts the N-terminal domain of the histone-binding protein RBBP4. Proteins containing this domain include members from the WD repeat RBAP46 (RBBP7)/RBAP48(RBBP4)/MSI1 family.RBBP4 is a subunit of the chromatin assembly factor 1 (CAF-1) complex. The CAF-1 complex is a conserved heterotrimeric protein complex that promotes histone H3 and H4 deposition onto newly synthesized DNA during replication or DNA repair; specifically it facilitates replication-dependent nucleosome assembly with the major histone H3 (H3.1). This domain is an alpha helix which sits just upstream of the WD40 seven-bladed β-propeller in the human RBBP7 protein. RBBP7 folds into the β-propeller and binds histone H4 in a groove formed between this N-terminal helix and an extended loop inserted into blade six [
].
Glycolipid transfer protein (GLTP) is a cytosolic protein that catalyses the intermembrane transfer of glycolipids such as glycosphingolipids, glyceroglycolipids, and possibly glucosylceramides, but not of phospholipids. The GLTP protein consists of a single domain with a multi-helical structure consisting of two layers of orthogonally packed helices [
,
]. The GLTP domain is also found in trans-Golgi network proteins involved in Golgi-to-cell-surface membrane traffic [
].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].This entry includes the eukaryotic ribosomal protein L14, which binds to the 60S ribosomal subunit.
This entry represents the C-terminal domain of protein dehydration-induced19 (Di19), a protein that increases the sensitivity of plants to environmental stress, such as salinity, drought, osmotic stress and cold. the protein is also induced by an increased supply of stress-related hormones such as abscisic acid ABA and ethylene [
]. There is a zinc-finger at the N terminus, Znf-Di19.
It is thought that NAPs act as histone chaperones, shuttling both core and linker histones from their site of synthesis in the cytoplasm to the nucleus. The proteins may be involved in regulating gene expression and therefore cellular differentiation [
,
].The centrosomal protein c-Nap1, also known as Cep250, has been implicated in the cell-cycle-regulated cohesion of microtubule-organizing centres. This 281kDa protein consists mainly of domains predicted to form coiled coil structures. The C-terminal region defines a novel histone-binding domain that is responsible for targeting CNAP1, and possibly condensin, to mitotic chromosomes [
]. During interphase, C-Nap1 localizes to the proximal ends of both parental centrioles, but it dissociates from these structures at the onset of mitosis. Re-association with centrioles then occurs in late telophase or at the very beginning of G1 phase, when daughter cells are still connected by post-mitotic bridges. Electron microscopic studies performed on isolated centrosomes suggest that a proteinaceous linker connects parental centrioles and C-Nap1 may be part of a linker structure that assures the cohesion of duplicated centrosomes during interphase, but that is dismantled upon centrosome separation at the onset of mitosis [].
Eaf6 is a component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of selected genes principally by acetylation of nucleosomal histone H4 and H2A. The NuA4 histone acetyltransferase complex is conserved from yeast to humans [
]. Budding yeast Eaf6 is also a component of the NuA3 histone acetyltransferase complex that acetylates Lys-14 of histone H3 [], while human Eaf6 is a component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity [].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].Ribosomal protein S7 is one of the proteins from the small ribosomal subunit.
In Escherichia coli, S7 is known to bind directly to part of the 3'end of 16Sribosomal RNA. It belongs to a family of ribosomal proteins which have been grouped on the
basis of sequence similarities [,
].This entry represents the S7 structural domain, which consists of a bundle of six helices and an extended beta hairpin between helices 3 and 4, with two or more RNA-binding sites on its surface [
].
Mammalian translationally controlled tumour protein (TCTP) (or P23) is a protein which has been found to be preferentially synthesised in cells during the early growth phase of some types of tumour [
,
], but which is also expressed in normal cells. The physiological function of TCTP is still not known. It was first identified as a histamine-releasing factor, acting in IgE +-dependent allergic reactions. In addition, TCTP has been shown to bind to tubulin in the cytoskeleton, has a high affinity for calcium, is the binding target for the antimalarial compound artemisinin, and is induced in vitamin D-dependent apoptosis. TCTP production is thought to be controlled at the translational as well as the transcriptional level []. TCTP is a hydrophilic protein of 18 to 20 kD. TCTPs do not share significant sequence similarity with any other class of proteins. Recently, the structure of TCTP was determined and exhibited significant structural similarity to the human protein Mss4, which is a guanine nucleotide-free chaperone of the Rab protein [
]. Close homologues have been found in plants [], earthworm [], Caenorhabditis elegans (F52H2.11), Hydra, Saccharomyces cerevisiae (YKL056c) [] and Schizosaccharomyces pombe (SpAC1F12.02c).
Rho GTPase activating protein 6 (ArhGAP6/RHOGAP6) shows GAP activity towards RhoA, but not towards Cdc42 and Rac1 [
]. ArhGAP6 is often deleted in microphthalmia with linear skin defects syndrome (MLS); MLS is a severe X-linked developmental disorder [].This family also includes ARHGAP36, which is a potent antagonist of PKA signalling [
].
This entry represents COMM domain-containing protein 8 (COMMD8) and similar animal proteins. COMMD8 is a member of the COMMD family defined by the presence of a conserved and unique motif termed the COMM (copper metabolism gene MURR1) domain, which functions as an interface for protein-protein interactions [
].
This family is found in SH (small hydrophobic) proteins present in Metapneumovirus such as the Avian metapneumovirus (AMPV), a paramyxovirus that has three membrane proteins (G, F, and SH). Among them, the SH protein is a small type II integral membrane protein. It is located in both the plasma membrane as well as within intracellular compartments. AMPV type C- SH protein localizes in the endoplasmic reticulum (ER), Golgi, and cell surface, and is transported through ER-Golgi secretory pathway. AMPV SH protein is modified by N-linked glycans and can be released into the extracellular environment. Furthermore, it has been shown that glycosylated AMPV SH proteins form homodimers through cysteine-mediated disulfide bonds [
].
Members of the cysteine/serine-rich nuclear protein family (CSRNP) contain cysteine- and serine-rich regions and a basic domain. They are nuclear proteins that possess a transcriptional activation domain and bind the sequence AGAGTG [
,
]. The proteins actively influence transcriptional activity, but it has not been established which of their domains are involved in DNA binding. It is thought that this may potentially be mediated by the conserved cysteine-rich or the basic domain.It has been shown that CSRNP genes are down-regulated in various different cancers, suggesting that they act as tumour suppressors [
]. This would usually imply a relation to reduced apoptosis, but this has yet to be proven; in some studies, a reduction in apoptosis was not detected as a result of deficiencies of CSRNP genes.
Cyclin-dependent kinase 2-interacting protein (CINP) is a component of the active cyclin E/Cdk2 and cyclin A/Cdk2 complexes [
]. It is phopshorylated by Cdc7, but not by Cdk2 []. CINP has also been shown to bind to chromatin in a replication-dependent manner, and to associate with Origin Recognition Complex-2 (ORC2)-containing complexes and minichromosome maintenance/DNA replication licensing complex, MCM []. It has been proposed that CINP is part of the Cdc7-dependent mechanism of origin firing, and constitutes a physical link between Cdk2 and Cdc7 complexes at the origins [].
Contact-dependent growth inhibition (CDI) toxins are expressed by Gram-negative bacteria as part of a mechanism to inhibit the growth of neighbouring bacteria. This entry includes the inhibitor (CdiI) of the CdiA effector protein from Escherichia coli EC869 (which is a DNAse). CdiA secretion is dependent on the outer membrane protein CdiB. Upon binding to a receptor on the surface of target bacteria, the CDI toxin is delivered. The inhibitors are intracellular proteins that inactivate the toxin/effector protein [
,
].The structure of Cdil is composed of two beta(3)-alpha motifs related by pseudo twofold symmetry, a single antiparrallel β-sheet, shaped into a half-barrel with a helical linker region.
NudCD1, also known as CML66 or OVA66, belongs to the NudC family, whose members share a conserved p23 domain. It is the more distant and less characterised family member. NudCD1 is a tumour associated antigen highly expressed in human leukaemia, some solid tumours and tumour cell lines [
]. Its expression in normal tissues is restricted to testis [,
]. Different NudCD1 isoforms have unique interacting partners, with the first isoform binding to a putative RNA helicase named DHX15 involved in mRNA splicing [].
This entry includes DENN domain-containing proteins 5A/B (DEN5A/B) from humans and similar animal proteins that belong to the RAB6 interacting protein 1 (Rab6IP1) family. DEN5A/B are guanine nucleotide exchange factors (GEFs) which may activate RAB6A and RAB39A and/or RAB39B. They promote the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form [
]. DEN5A is involved in the negative regulation of neurite outgrowth [].
Gram-negative bacteria such as Vibrio cholera require the production of a number of virulence factors during infection. The ToxR and ToxS regulatory proteins control the expression of the master virulence regulator ToxT. ToxS serves as a mediator of ToxR function, perhaps by influencing its stability and/or capacity to dimerize [
].
This entry represents heat shock protein 15 (Hsp15), an abundant nucleic acid-binding protein whose RNA synthesis is induced upon temperature upshift [
,
]. The protein contains an RNA-binding motif []. The in vivo target of Hsp15 appears to be the free 50S ribosomal subunit - it does not bind it when it is part of the 70S ribosome []. Hsp15 may be involved in the recycling of free 50S subunits that still carry a nascent chain [].
These sequences describe the flagellar biosynthesis protein FlhA, one of a large number of genes associated with the biosynthesis of functional bacterial flagella. FlhA is an integral membrane protein of the export apparatus and is involved in an early stage of the export process along with three soluble proteins, FliH, FliI, and FliJ [
]. FlhA functions in type III protein secretion systems.
Pulmonary surfactant associated proteins promote alveolar stability by lowering the surface tension at the air-liquid interface in the peripheral air spaces. SP-C, a component of surfactant, is a highly hydrophobic peptide of 35 amino acid residues which is processed from a larger precursor protein. SP-C is post-translationally modified by the covalent attachment of two palmitoyl groups on two adjacent cysteines [
,
].
Orthobunyavirus are enveloped viruses with a genome consisting of 3 ssRNA segments (called L, M and S). The nucleocapsid protein (also known as nucleoprotein) is encoded on the small (S) genomic RNA. The N protein is the major component of the nucleocapsids. This protein is thought to interact with the L protein, virus RNA and/or other N proteins [
].
This family includes members encoded by ASP-related genes which are distant homologues to ASPs (Ancylostoma-associated secreted proteins). ASPRs are predicted to be secreted, with one ASPR in Heligmosomoides bakeri shown to be secreted by parasitic adults. Thus, like ASPs, ASPRs are suggested to comprise an important element of hookworm infection in vivo [
].
Antifungal protein consists of five antiparallel beta strands which are highly twisted creating a beta 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 []. This superfamily represents an antifungal protein lysine rich domain, that contributes to the correct folding of the protein, which is necessary for its specific antifungal activity. It has been suggested that this domain might contribute to the cell wall and/or nucleic acids binding activity [
].
This is a family of closely related high pH (HPH) proteins that are integral endoplasmic reticulum (ER) membrane proteins required for yeast survival under environmental stress conditions [
]. They interact with several subunits of the Sec63/Sec62 complex that mediates post-translational translocation of proteins into the ER []. Cells with mutant Hph1 and Hph2 proteins reveal phenotypes resembling those of mutants defective for vacuolar proton ATPase (V-ATPase) activity. The yeast V-ATPase is a multisubunit complex whose function, structure, and assembly have been well characterised. Cells with impaired V-ATPase activity fail to acidify the vacuole, cannot grow at alkaline pH, and are sensitive to high concentrations of extracellular calcium.
This entry represents PP2A-like family of phosphoprotein phosphatases (PPPs) which includes PP2A, PP4 and PP6, which are more closely related in sequence to one another than they are to the other PPPs [
]. PP2A (Protein phosphatase 2A) is a critical regulator of many cellular activities, and together with protein phosphatase 1 (PP1), accounts for more than 90% of all serine/threonine phosphatase activities in most cells and tissues. The PP2A subunit has a catalytic domain homologous to PP1 and a unique C-terminal tail, containing a motif that is conserved in the catalytic subunits of all PP2A-like phosphatases including PP4 and PP6, and has an important role in PP2A regulation. The PP2A-like family of phosphatases all share a similar heterotrimeric architecture, that includes: a 65kDa scaffolding subunit (A), a 36kDa catalytic subunit (C), and one of 18 regulatory subunits (B). The PPP (phosphoprotein phosphatase) family, to which PP2A belongs, is one of two known protein phosphatase families specific for serine and threonine. PP2A is the major phosphatase for microtubule-associated proteins (MAPs) [].PP4 (also known as protein phosphatase X) is a phosphatase involved in many processes such as microtubule organization at centrosomes, maturation of spliceosomal snRNPs, apoptosis, DNA repair, tumour necrosis factor (TNF)-alpha signalling, activation of c-Jun N-terminal kinase MAPK8, regulation of histone acetylation, DNA damage checkpoint signalling, NF-kappa-B activation and cell migration. The PPP4C-PPP4R1 PP4 complex may play a role in dephosphorylation and regulation of HDAC3. The PPP4C-PPP4R2-PPP4R3A PP4 complex specifically dephosphorylates H2AX phosphorylated on Ser-140 (gamma-H2AX) generated during DNA replication and required for DNA double strand break repair [
,
,
].PP6 is a component of a signaling pathway regulating cell cycle progression in response to IL2 receptor stimulation [
]. It also regulates innate immunity by acting as a negative regulator of the cGAS-STING pathway as it mediates dephosphorylation and inactivation of CGAS and STING1 [,
].
This entry represents RING finger protein 141 from human (RNF141, also known as ZNF230) and similar RING-type zinc finger containing proteins predominantly found in eukaryotes. RNF141 may be involved in spermatogenesis [].
This group represents complement control proteins, vaccinia virus C3-type. The vaccinia virus complement control protein C3 is involved in modulating the host inflammatory response by blocking both classical and alternative pathways of complement activity through its ability to bind host complement components C3b and C4b (complement 3b and 4b, respectively) [
]. Protein B5, another member of this group, binds complement components C3 and C1q []. By blocking complement activation at multiple sites, the complement control proteins can down-regulate pro-inflammatory chemotactic factors (C3a, C4a, and C5a), resulting in reduced cellular influx and inflammation..
ComS is crucial for competence development as it prevents proteolytic degradation of ComK, the key transcriptional activator of all genes required for the uptake and integration of DNA. This family includes members of the Bacillus ComS proteins such as
[
].
This entry represents a protein family that includes the transcription factors Forkhead box protein N2-4 from humans (FOXN2-4) and related proteins from animals [
,
]. Putative forkhead-related transcription factor fkh-5 from Caenorhabditis elegans, an orthologue of human FOXN4, is also included in this entry. FOXN4 is a transcription factor essential for neural and some non-neural tissues development, such as retina and lung respectively. It binds to a consensus sequence containing the invariant tetranucleotide 5'-ACGC-3'. During development of the central nervous system, is required to specify the amacrine and horizontal cell fates from multipotent retinal progenitors while suppressing the alternative photoreceptor cell fates through activating DLL4-NOTCH signaling [,
].
This family includes F-box only protein 7 from humans (Fbxo7) and similar animal proteins. Fbxo7 is 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. It plays a role in the clearance of damaged mitochondria via selective autophagy (mitophagy). Mutations in this protein lead to Parkinson's disease [
,
,
,
].
Family members are found in strongylid parasites (A. ceylanicum, N. americanus, H. contortus and Heterorhabditis bacteriophora) and in related non-parasitic clade V species (C. elegans, Caenorhabditis briggsae and P. pacificus), hence the name secreted clade V proteins (SCVPs). In Ancylostoma ceylanicum, the encoded 150 residue proteins are predicted to be classically secreted [
].
Family members are predicted non-classically secreted proteins found in Ancylostoma ceylaniucum. Homologs are found in strongylids A. ceylanicum, N. americanus, H. contortus and Angiostrongylus cantonensis, where the corresponding genes in A. cantonensis are expressed in L4 larvae. Thus this family members found in A. ceylaniucum have been named strongylid L4 proteins (SL4Ps). Although SL4Ps do not resemble any domains of known function, they do have a conspicuous number of charged residues (both acidic and basic) in their N-terminal, most highly conserved regions [
].
The chlamydial inclusion membrane is extensively modified by the insertion of type III secreted effector proteins [
]. These inclusion membrane proteins (Incs) have two major characteristics: an N-terminal type III secretion signal that is necessary for their secretion out of the bacterium and a hydrophobic region consisting of at least two trans-membrane helices that allows insertion into the inclusion membrane. Generally, both the N- and C-terminal regions of the Inc are exposed to the host cell cytosol [].This family has members such as the IncD proteins found in Chlamydia trachomatis. This C. trachomatis effector protein IncD has been shown to recruit the lipid transfer protein CERT to the inclusion membrane by directly interacting with CERT PH domain, which mediates the FFAT motif-dependent recruitment of the ER-resident protein VAPB (vesicle-associated membrane protein-associated protein) to the inclusion [
].
The chlamydial inclusion membrane is extensively modified by the insertion of type III secreted effector proteins [
]. These inclusion membrane proteins (Incs) have two major characteristics: an N-terminal type III secretion signal that is necessary for their secretion out of the bacterium and a hydrophobic region consisting of at least two trans-membrane helices that allows insertion into the inclusion membrane. Generally, both the N- and C-terminal regions of the Inc are exposed to the host cell cytosol [].This family has members such as the IncE (also known as CT116) proteins found in Chlamydia trachomatis. IncE Interacts with Retromer-Associated Sorting Nexins (SNXs) directly binding the PX-domains of SNX5/6. It is expressed within the first 2 hours of C. trachomatis infection. IncE region 101-132 is the binding site for SNX5/6 causing re-localization of SNX5/6 from endosomes to the inclusion membrane. IncE101-132 expression was shown to be sufficient to maintain CI-MPR (Cation-Independent Mannose-6-Phosphate Receptor) in retromer-containing compartments, thereby disrupting efficient CI-MPR trafficking to the trans-Golgi. It has been suggested that SNX5/6 bind directly to IncE independently of phosphoinositides and that the predicted IncE C-terminal β-hairpin is required. IncE-mediated sequestration of retromer SNX-BAR proteins may promote Golgi fragmentation, a process that facilitates lipid acquisition by C. trachomatis and enhances progeny production [].
The chlamydial inclusion membrane is extensively modified by the insertion of type III secreted effector proteins. These inclusion membrane proteins (Incs) are exposed to the cytosol and share a common structural feature of a long, bi-lobed hydrophobic domain but little or no primary amino acid sequence similarity [
].This family has members such as the IncF proteins found in Chlamydia trachomatis. IncF is enriched at the point of contact of RBs (reticulate bodies) with the inclusion membrane [
]. It is expressed early in the developmental cycle and interacts with many other Inc proteins, like Ct058 or Ct850, which are expressed later during the cycle. Thus, IncF could act as an interaction node for Inc proteins. IncF consists of 104 amino acids of which 38 N-terminal amino acids encoding the signal sequence for the type III system and 12 C-terminal amino acids may be localized in the host cell cytoplasm. Suggesting that IncF or other small Incs interact with other Inc proteins by their trans-membrane domain. It has been identified to be capable of homo-oligomerization and also displayed self-interacting properties [].
This is a family of conserved fungal proteins which contain DUF3818 and PXA domains, including YPR097W from budding yeast and C663.15c/C1450.12 from fission yeast. According to SGD database, YPR097W may play a role in regulating the distribution of ergosterol in yeast cells, and it has been suggested to name it Lec1 for Lipid-droplet Ergosterol Cortex 1.
Protein 17 (gene product 17/gp17), found in Bacillus phage phi29, is involved in DNA replication and in pulling the phage DNA into the cell during the injection process [
].
This entry represents a group of GTPase-activating proteins (GAPs) that stimulate the GTPase activity of Rho-type GTPases, including Rho GTPase-activating protein 17 (RHG17, also known as RICH-1), RHG44 (also known as RICH-2), SH3 domain-binding protein 1 (SH3BP1) and bargin from human which are referred to as BAR-domain RhoGAP subfamily [
]. Bargin is an alternative splice product consisting of a modified N-terminal BAR domain, an intermediary RhoGAP domain, and a C-terminal partial CIN module and this is the only BAR-RhoGAP subfamily member that lacks a C-terminal polyproline-rich repeat region, which is replaced by the partial CIN phosphatase module [].These proteins convert GTP-bound Rho-type GTPases including RAC1 and CDC42 in their inactive GDP-bound form. SH3BP1 specifically inactivates RAC1 at the leading edge of migrating cells, it regulates the spatiotemporal organization of cell protrusions which is important for proper cell migration [
]. It is involved in actin remodelling and the formation of epithelial cell junctions, through negative regulation of CDC42 [,
]]. This protein plays a specific role in phagocytosis of large particles as it is specifically recruited by a PI3 kinase/PI3K-dependent mechanism to sites of large particles engagement, where it inactivates RAC1 and/or CDC42 allowing the reorganization of the actin cytoskeleton required for engulfment [].
This entry represents ARF GTPase-activating protein Git from Drosophila melanogaster, ARF GTPase-activating protein GIT1/2 from humans, and similar proteins from animals. Git is a GTPase-activating protein for ADP ribosylation factor family members, including ARF1. It promotes proper muscle morphogenesis and proper guidance and targeting of subsets of myotubes [
]. Git may be important for brain development []. GIT1 plays an important role in dendritic spine morphogenesis and synapse formation [,
]. It plays a crucial role in regulating GABA(A) receptor synaptic stability, leading to F-actin stabilization []. It may also may regulate activation of the canonical NF-kappa-B signal in bone mesenchymal stem cells, eventually leading to enhanced production of VEGFA and other angiogenic factors [].
This entry represents F-box only protein 5 and 43 (FBX5/43, also known as Emi1/Emi2, respectively [
]) from human and similar proteins from animals. FBX5 is a regulator of the anaphase-promoting complex (APC) activity during mitotic and meiotic cell cycle [,
,
,
,
,
]. It promotes migration and osteogenic differentiation of mesenchymal stem cells []. FBX43 is required to establish and maintain the arrest of oocytes at the second meiotic metaphase until fertilization. This protein acts by inhibiting the APC/cyclosome ubiquitin ligase. It probably recognises and binds to some phosphorylated proteins and promotes their ubiquitination and degradation [,
].
There are currently no experimental data for members of this group or their homologues, nor do they exhibit
features indicative of any function. Members of this group are restricted to the Proteobacteria.
This family includes FERM domain-containing protein 6 (FRMD6, also known as willin and hEx/human expanded), its homologue from Drosophila, Expanded (Ex) and FERM domain-containing protein 1 (FRMD1). Ex, is a regulator of the Hippo/SWH (Sav/Wts/Hpo) signalling pathway, which plays a pivotal role in organ size control and is tumour suppression by restricting proliferation and promoting apoptosis [,
]. Human FRMD6 was first thought to function independently of the Hippo pathway as it lacks the C-terminal domain of Ex that allows it to directly interact with various downstream Hippo signalling components [,
]. However, it has been shown to act as an upstream regulator of Hippo signalling that modulates actin cytoskeleton dynamics and mechanical phenotype of neuronal cells through ERK signalling []. FRMD6 is widely distributed in various tissues and cell types; in the nervous system is involved in neuronal differentiation, myelination, nerve injury repair, and vesicle exocytosis. It has been implicated in the progression of Alzheimer's disease (AD) [] and positioned as a novel AD risk gene [].There is not much information about FRMD1 to date. Both FRMD1 and FRMD6 contain a single FERM domain, which is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin.
This group of proteins contains a VWA type domain and the function of this family is unknown. It is found as part of a CO oxidising (Cox) system operon in several bacteria [
].
This entry includes FRMD4A/B from humans and mice, and similar animal proteins. FERM domain-containing protein 4A (FRMD4A) is part of the Par-3/FRMD4A/cytohesin-1 complex that activates Arf6, a central player in actin cytoskeleton dynamics and membrane trafficking, during junctional remodelling and epithelial polarization. The Par-3/Par-6/aPKC/Cdc42 complex regulates the conversion of primordial adherens junctions (AJs) into belt-like AJs and the formation of linear actin cables. When primordial AJs are formed, Par-3 recruits scaffolding protein FRMD4A which connects Par-3 and the Arf6 guanine-nucleotide exchange factor (GEF), cytohesin-1 [
].FERM domain-containing protein 4B (FRMD4B, also called GRP1-binding protein, GRSP1) is a novel member of GRP1 signalling complexes that are recruited to plasma membrane ruffles in response to insulin receptor signalling. The GRSP1/FRMD4B protein contains a FERM protein domain as well as two coiled coil domains and may function as a scaffolding protein. GRP1 and GRSP1 interact through the coiled coil domains in the two proteins [
].
Members of this family belong to a large group that also contains thiamine monophosphate kinase, hydrogenase maturation factor HypE (
), AIR synthase, FGAM synthase (
), selenophosphate synthetase (
), and other groups. In AIR synthase, the N-terminal domain forms the dimer interface of the protein and, upon dimerisation, forms the putative ATP binding domain, while the cleft formed between the N- and C-terminal domains is postulated to be a sulphate binding site [
]. It could be speculated that similar structure-function relationship exists in members of this family; however, there is no experimental data that proves the biochemical activity.
This domain is found in the Bacilli coat protein X as a tandem repeat and as a single domain in coat protein V. The proteins are found in the insoluble fraction [
].
Many enterobacteria are able to convert carnitine, via crotonobetaine, to gamma-butyrobetaine in the presence of carbon and nitrogen sources under anaerobic conditions [
]. In Escherichia coli the enzymes involved in this pathway are encoded by the caiTABCDE operon []. The adjacent but divergent fixABCD operon also appears to be necessary for carnintine meatbolism []. The Fix proteins are homologous to proteins found in known electron transport pathways.The function of the CaiE protein is not known, but overexpression has been shown to stimulate the activity of CaiB and CaiD proteins [
,
,
].
This family consists of Gammaproteobacterial proteins. Members of the family are predicted to be G5P DNA binding proteins. Homologous proteins are found in
.
DNA replication of phi29 and related phages takes place via a strand displacement mechanism, a process that generates large amounts of single-stranded DNA (ssDNA). Consequently, phage-encoded ssDNA-binding proteins (SSBs) are essential proteins during phage phi29-like DNA replication. Single-stranded DNA-binding proteins (SSBs) destabilize double-stranded DNA (dsDNA) and bind without sequence specificity, but selectively and cooperatively, to single-stranded DNA (ssDNA) conferring a regular structure to it, which is recognized and exploited by a variety of enzymes involved in DNA replication, repair and recombination.Phage phi29 protein p5 is the SSB protein active during phi29 DNA replication. It protects ssDNA against nuclease degradation and greatly stimulates dNTP incorporation during phi29 DNA replication process. Binding of the SSB to ssDNA prevents non-productive binding of the viral DNA polymerase to ssDNA, and allows the release DNA polymerase molecules that are already titrated by the ssDNA. This effect would be of particular importance in phi29-like DNA replication systems, where large amounts of ssDNA are generated and SSB binding to ssDNA could favor efficient re-usage of templates [
].This domain is found in phi29-like SSB proteins, homologues are found in
.
This domain is found in several bacterial FlgE flagellar hook proteins [
]. The flagellar hook is a short, curved, extracellular structure located between the basal body and the filament [].
This entry contains a group of prokaryotic proteins that share protein sequence similarity to eukaryotic Nuclear protein AMMECR1, including Protein PH0010 from Pyrococcus horikoshii. PH0010 consists of two distinct domains of different
sizes: the large domain, which contains both the N- and C-terminal regions, consists of five α-helices and five β-strands that form an antiparallel β-sheet; the small domain consists of four α-helices and three β-strands that also form an antiparallel β-sheet [,
].
This entry represents the putative ribosomal L7e family found in selected Gram-positive bacteria.Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].
This family of proteins appear to be specific to Schizosaccharomyces (Fission yeast). Their exact function is unknown, but they are up-regulated in meiosis and some of them have been shown to be required for critical meiotic events [
].
This family of bacterial proteins is functionally uncharacterised. Proteins in this family are approximately 100 amino acids in length. There is a conserved FGIGF sequence motif, and many members are putative membrane proteins.
This family includes superinfection exclusion proteins. These proteins prevent the growth of superinfecting phage which are insensitive to repression. It aborts lytic development of superinfecting phage [
,
,
].
The PhnA protein family includes the uncharacterised Escherichia coli protein PhnA and its homologues. The E. coli phnA gene is part of a large operon associated with alkylphosphonate uptake and carbon-phosphorus bond cleavage [
]. The protein is not related to the characterised phosphonoacetate hydrolase designated PhnA [].This entry represents the N-terminal domain of PhnA proteins, which is predicted to form a zinc-ribbon, found in some proteobacteria. It does not include the E. coli sequence.
Proteins containing this domain include the SusE outer membrane protein from Bacteroides thetaiotaomicron,
. This protein has a role in starch utilisation, but is not essential for growth on starch [
].
CRADD (Caspase and RIP adaptor, also known as RAIDD) is an adaptor protein that together with the p53-inducible protein PIDD and caspase-2, forms the PIDDosome complex, which is required for caspase-2 activation and plays a role in mediating stress-induced apoptosis [
]. It contains an N-terminal CARD, which interacts with the caspase-2 CARD, and a C-terminal Death domain (DD), which interacts with the DD of PIDD [].
Rec104 is one of several meiosis specific genes required for generating meiotic DSBs (double strand breaks) [
]. It is suggested that Rec102 and Rec104 directly promote DSB formation as part of a multiprotein complex with Spo11. Rec102 and Rec104 are mutually dependent for proper sub-cellular localization, and share a requirement for Spo11 and Ski8 for their recruitment to meiotic chromosomes. Moreover, Rec102 is required for Rec104 to accumulate to normal steady-state levels and to be properly phosphorylated. It is likely that Rec102 and Rec104 move freely in and out of the nucleus but are most stably sequestered there only when they can form a complex on chromosomes [].
Satellite RNAs (satRNAs) are short RNA molecules, usually larger than 1,500 nt, that depend on cognate helper viruses for replication, encapsidation, movement, and transmission, but most share little or no sequence homology to the helper viruses. In contrast, satellite viruses are satRNAs that encode and are encapsidated in their own capsid proteins (CPs) [
]. Members of this family are nonstructural proteins of 48kDa in size which have been shown to be involved in the replication of the sat-RNA. They are found in tomato black ring virus (TBRV) [].
The exact function of the MauJ proteins is unknown but thought to be involved in methylamine utilization. MauJ is predicted to be a cytoplasmic protein.
SwrA is a transcription factor involved in swarming motility (a multicellular movement of hyper-flagellated cells on a surface). It acts synergistically with DegU to drive the fla/che operon encoding flagella components, chemotaxis constituents and the alternative sigma factor sigmaD, which is regarded as the primary event in the development of motility [
]. LonA protease of Bacillus subtilis inhibits SwrA by proteolytically restricting its accumulation []. SwrA does not contain any known DNA binding domain, and it has been shown to interact with the N-terminal domain of DegU. Anecdotally, in most laboratory strains, e.g. 168, the swrA coding sequence contains a nucleotide insertion that prematurely interrupts its reading frame, causing a non-swarming phenotype strain [].
This region is found in a number of hypothetical proteins thought to be expressed by the eukaryote Encephalitozoon cuniculi, an obligate intracellular microsporidial parasite. The proteins are approximately 200 residues long.
This family of hypothetical bacterial and archaeal proteins have no known function. One family member,
, is annotated as being one subunit of an H+-transporting two-sector ATPase, but it is not clear where this information comes from and no evidence has been found to support this claim.
In Chlamydomonas reinhardtii, the gene encoding
is induced by iron deficiency [
]. In green algae, this protein is periplasmic. The two paralogues FEA1 and FEA2 are the major proteins secreted by iron-deficient Chlamydomonas reinhardtii, and both are up-regulated in response to iron deficiency. FEA1 but not FEA2 is up-regulated by high CO2 concentration. Both FEA1 and FEA2 are secreted into the periplasmic space and genetic evidence confirms that their association with the cell is required for growth in low iron [].
KaiA is a component of the kaiABC clock protein complex, which constitutes the main circadian regulator in cyanobacteria. The kaiABC complex may act as a promoter-nonspecific transcription regulator that represses transcription, possibly by acting on the state of chromosome compaction. In the complex, KaiA enhances the phosphorylation status of kaiC. In contrast, the presence of kaiB in the complex decreases the phosphorylation status of kaiC, suggesting that kaiB acts by antagonising the interaction between kaiA and kaiC. The activity of KaiA activates kaiBC expression, while KaiC represses it. The overall fold of the KaiA monomer is that of a four-helix bundle, which forms a dimer in the known structure [
]. KaiA functions as a homodimer. Each monomer is composed of three functional domains: the N-terminal amplitude-amplifier domain, the central period-adjuster domain and the C-termianl clock-oscillator domain. The N-terminal domain of KaiA, from cyanobacteria, acts as a psuedo-receiver domain, but lacks the conserved aspartyl residue required for phosphotransfer in response regulators []. The C-terminal domain is responsible for dimer formation, binding to KaiC, enhancing KaiC phosphorylation and generating the circadian oscillations []. The KaiA protein from Anabaena sp. (strain PCC 7120) lacks the N-terminal CheY-like domain.
The G3P protein (also known as attachment protein or coat protein A) of filamentous phage such as M13, phage fd and phage f1, is an essential coat protein for the infection of Escherichia coli. The G3P protein consists of three domains: two N-terminal domains (N1 and N2) with a similar β-barrel fold, and a C-terminal domain [
]. The N-terminal domains protrude from the phage surface, while the C-terminal domain acts as an anchor embedded in the phage coat, together forming a horseshoe-like structure []. The G3P protein exists as 3-5 copies at the tip of the phage particle. Infection by filamentous phage involves two distinct cellular receptors, the F' pilus and the periplasmic protein TolA, which are bound sequentially [
]. The N2 domain binds the F' pilus, causing a conformational change which allows the N1 domain to bind the C-terminal domain of TolA as a co-receptor.This entry represents the two N-terminal domains, N1 and N2, of G3P.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].This family represents the archaeal L40e ribosomal protein [
].
This entry represents mitochondrial division protein 1 (Mdv1), which is a component of the mitochondrial fission machinery in Saccharomyces cerevisiae. The protein is also involved in peroxisome proliferation []. Mdv1 along with Fis1 is also involved in controlling Dnm-1 dependent devision, a GTPase involved in the mediation of mitochondrial division. In this role, Mdv1 is the linker between Fis1 and Dnm1. Mdv1 plays a key role in the regulation of Dnm1 self-assembly [].Mdv1 has a partially redundant function to CAF4 in acting as an adapter protein, binding to FIS1 on the mitochondrial outer membrane and recruiting the dynamin-like GTPase DNM1 to form mitochondrial fission complexes. Formation of these complexes is required to promote constriction and fission of the mitochondrial compartment at a late step in mitochondrial division [
,
]. Mdv1 interacts with CAF4, DNM1 and FIS1, components of the mitochondrial fission machinery. It interacts via its N-terminal, coiled-coil extension (NTE) with FIS1, and via its WD repeats with DNM1. Mdv1 is uniformly distributed on the cytoplasmic face of the mitochondrial outer membrane. This localisation is dependent on FIS1. It reorganises to punctate structures on mitochondria, corresponding to mitochondrial constriction sites, at a late step in mitochondrial division. This relocalisation is dependent on DNM1.
