Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].This family consists of archaeal ribosomal L10e proteins.
The active zone is the presynaptic region in the nerve terminals that mediates neurotransmitter release and is composed a dense collection of proteins called the cytomatrix at the active zone (CAZ). The CAZ proteins are thought to mediate synapse formation and regulate neurotransmitter release [
,
].This entry represents the ELKS family, which are thought to be involved in the organisation of CAZ. Vertebrate ELKS proteins are produced by two genes, ERC1 and ERC2. Caenorhabditis elegans expresses a homologue of ELKS that acts downstream of syd2/liprin-alpha during active zone assembly [
]. Drosophila melanogaster expresses a related protein termed bruchpilot (brp) that consists of a conserved N terminus and a C-terminal half with no homologous sequences in vertebrates. Brp is required for structural integrity and function of synaptic active zones []. Vertebrate ELKS proteins are enriched at presynaptic active zones [] and support Ca2+ influx at nerve terminals of inhibitory hippocampal neurons []. They have a C-terminal PDZ-binding motif that binds directly to RIM (a small G protein Rab-3A effector). These proteins also contain four coiled-coil domains [].
This entry represents a group of uncharacterised proteins, such as the 9.3kDa protein YNQ1 from the nqo2 3'region in Paracoccus denitrificans. They have no known function.
This family includes the accessory protein NS6 from deltacoronaviruses such as porcine coronavirus HKU15, and several avian coronaviruses found in sparrow, pigeon, quail and falcon, among others.
Porcine deltacoronavirus (PDCoV) encodes three accessory proteins, NS6, NS7, and NS7a. During PDCoV infection, NS6 antagonizes RIG-I-like receptor (RLR)-mediated IFN-beta production to evade host innate immune defense; it interacts with RIG-I and MDA5 to impede their association with double-stranded RNA. This is an important finding towards novel therapeutic targets and may lead to the development of more effective vaccines against PDCoV infection [
].
GDP-fucose protein O-fucosyltransferase 1 (POFUT1) transfers fucose residues to acceptor sites on serine and threonine residues of epidermal growth factor-like repeats of recipient proteins. It is essential for Notch signal transduction in mammals [
]. Mutations in the POFUT1 gene cause Dowling-Degos disease 2 (DDD2), a type of rare autosomal-dominant genodermatosis characterised by reticular hyperpigmentation and hypopigmentation of the flexures []. The structure of POFUT1 has been determined [].
Protein O-fucosylation is a post-translational modification found on serine/threonine residues of thrombospondin type 1 repeats (TSR). The fucose transfer is catalysed by the protein O-fucosyltransferase 2 (POFUT2) [
]. POFUT2 is required for the proper secretion of ADAMTS (a disintegrin and metalloproteinase with thrombospondin type 1 repeats) family members such as ADAMSL1 and ADAMST13 [,
].
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 is a family of short mitochondrial ribosomal proteins, less than 200 amino acids long. MRP-S35 was proposed as a more appropriate name to this group of proteins [
].
MRP-L51 is a family of small proteins from the intact 55 S mitochondrial ribosome [
]. It has otherwise been referred to as bMRP-64 []. The exact function of this family is not known.
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 is the conserved N terminus and central portion of the mitochondrial small subunit 28S ribosomal protein S22. Mammalian mitochondria carry out the synthesis of 13 polypeptides that are essential for oxidative phosphorylation and, hence, for the synthesis of the majority of the ATP used by eukaryotic organisms. The number of proteins produced by prokaryotes is smaller, reflected in the lower number of ribosomal proteins present in them [
].
This entry represents the non-structural protein ORF5 from Middle East respiratory syndrome-related coronavirus (MERS-CoV) and similar proteins from betacoronaviruses in the merbecovirus subgenera (C lineage). ORF5 is also called non-structural protein 3d (NS3d) or accessory protein 3d in some bat merbecoviruses. MERS-CoV is a highly pathogenic respiratory virus with pathogenic mechanisms that may be driven by innate immune pathways. MERS-CoV ORF5 acts as an interferon antagonist and may play a role in circumventing the innate immunity of host cells [
,
]. ORF5/NS3d from merbecovirus (betacoronavirus, lineage C) may not be related to ORF5 proteins from other lineages.
Proteins containing this domain include coronavirus (CoV) non-structural protein 5 (NSP5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), from gammacoronaviruses [
,
].CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/NSP5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/NSP5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of α-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/NSP5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs [,
,
,
,
].
Proteins containing this domain include (CoV) non-structural protein 5 (NSP5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in alphacoronaviruses [
,
,
,
,
,
,
,
,
,
,
,
,
].CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/NSP5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/NSP5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of α-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/NSP5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs [
,
,
,
,
].
Proteins containing this domain include the coronavirus (CoV) non-structural protein 5 (NSP5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in deltacoronaviruses [
,
,
].CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/NSP5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/NSP5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of α-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/NSP5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs [
,
,
,
,
].
This entry represents a group of plant zinc finger proteins, including ZAT1/4/9 from Arabidopsis. They may regulate the maturation of the outermost cells of the root cap in Arabidopsis [
]. Overexpression of ZAT1 has been shown to induce the ectopic expression of PUTATIVE ASPARTIC PROTEASE3 involved in the programmed cell death. ZAT1 possesses two conserved EAR motifs, the second EAR motif is essential for the growth inhibition by ZAT1 [].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].This entry represents a family of conserved proteins which were originally described as death-associated-protein-3 (DAP-3). The proteins carry a P-loop DNA-binding motif, and induce apoptosis [
]. DAP3 has been shown to be a pro-apoptotic factor in the mitochondrial matrix [] and to be crucial for mitochondrial biogenesis and so has also been designated as MRP-S29 (mitochondrial ribosomal protein subunit 29).
The functions of NSP2 remain unclear. SARS-CoV NSP2, rather than playing a role in viral replication, may be involved in altering the host cell environment; deletion of NSP2 from the SARS-CoV genome results in only a modest reduction in viral titers, and it has been shown to interact with two host proteins, prohibitin 1 (PHB1) and PHB2 which have been implicated in cellular functions, including cell-cycle progression, cell migration, cellular differentiation, apoptosis, and mitochondrial biogenesis [
,
]. MHV NSP2, also known as p65, different from SARS-CoV NSP2, may play an important role in the viral life cycle [].This entry represents NSP2 from Middle East respiratory syndrome-related coronavirus (MERS-CoV) and betacoronaviruses in the merbecovirus subgenera (C lineage).
The functions of NSP2 remain unclear. SARS-CoV NSP2, rather than playing a role in viral replication, may be involved in altering the host cell environment; deletion of NSP2 from the SARS-CoV genome results in only a modest reduction in viral titers, and it has been shown to interact with two host proteins, prohibitin 1 (PHB1) and PHB2 which have been implicated in cellular functions, including cell-cycle progression, cell migration, cellular differentiation, apoptosis, and mitochondrial biogenesis [
,
]. MHV NSP2, also known as p65, different from SARS-CoV NSP2, may play an important role in the viral life cycle [].This entry represents non-structural protein 2 (NSP2) from Severe acute respiratory syndrome coronavirus (SARS-CoV) and betacoronaviruses in the sarbecovirus subgenera (B lineage). In SARS-CoV-2, this protein coopts the GIGYF2/4EHP complex, which suppresses IFN-beta and, therefore, leads to evasion of a cellular innate immune response [
].
The functions of NSP2 remain unclear. SARS-CoV NSP2, rather than playing a role in viral replication, may be involved in altering the host cell environment; deletion of NSP2 from the SARS-CoV genome results in only a modest reduction in viral titers, and it has been shown to interact with two host proteins, prohibitin 1 (PHB1) and PHB2 which have been implicated in cellular functions, including cell-cycle progression, cell migration, cellular differentiation, apoptosis, and mitochondrial biogenesis [
,
]. MHV NSP2, also known as p65, different from SARS-CoV NSP2, may play an important role in the viral life cycle [].This entry represents NSP2 from Murine hepatitis virus (MHV) and betacoronaviruses in the embecovirus subgenera (A lineage).
This entry represents NSP2 from alphacoronavirus, including human coronavirus 229E (HCoV-229E), Porcine epidemic diarrhea virus and related viruses [
].The functions of NSP2 remain unclear. SARS-CoV NSP2, rather than playing a role in viral replication, may be involved in altering the host cell environment; deletion of NSP2 from the SARS-CoV genome results in only a modest reduction in viral titers, and it has been shown to interact with two host proteins, prohibitin 1 (PHB1) and PHB2 which have been implicated in cellular functions, including cell-cycle progression, cell migration, cellular differentiation, apoptosis, and mitochondrial biogenesis [
,
]. MHV NSP2, also known as p65, different from SARS-CoV NSP2, may play an important role in the viral life cycle [].
Avian infectious bronchitis virus (IBV) is a gammacoronavirus that belongs to Group III of coronaviruses. As all coronaviruses, they have a large genome containing the replicase gene consisting of two large ORFs, ORF1a and 1b that encode two replicase polyproteins ppa1a/1ab, which are then autoproteolytically processed into 15 or 16 matured nonstructural proteins to achieve viral genomic replication, assembly and maturation. This group contains avian viruses and differs from the other groups in that they do not encode the essential pathogenic factor nonstructural protein 1 (NSP1) and instead start with NSP2. IBV NSP2 is one of the first replicase proteins to be translated and processed in the viral life cycle []. NSP2 is a weak protein kinase R (PKR) antagonist, which may suggest that it plays a role in interfering with intracellular immunity [].This entry represents the nonstructural protein 2 (NSP2) from Avian infectious bronchitis virus (IBV) and related viruses which belong to gamma and deltacoronaviruses genera.
Avian infectious bronchitis virus (IBV) is a gammacoronavirus that belongs to Group III of coronaviruses. As all coronaviruses, they have a large genome containing the replicase gene consisting of two large ORFs, ORF1a and 1b that encode two replicase polyproteins ppa1a/1ab, which are then autoproteolytically processed into 15 or 16 matured nonstructural proteins to achieve viral genomic replication, assembly and maturation. This group contains avian viruses and differs from the other groups in that they do not encode the essential pathogenic factor nonstructural protein 1 (NSP1) and instead start with NSP2. IBV NSP2 is one of the first replicase proteins to be translated and processed in the viral life cycle [
]. NSP2 is a weak protein kinase R (PKR) antagonist, which may suggest that it plays a role in interfering with intracellular immunity [].
This entry contains the Escherichia coli gene yajB, now renamed acpH, which encodes an ACP hydrolase. AcpH converts holo-ACP to apo-ACP by hydrolytic cleavage of the phosphopantetheine prosthetic group from ACP [
].A mutant E. coli strain having a total deletion of the acpH grows normally, showing that phosphodiesterase activity is not essential for growth, although it is required for turnover of the ACP prosthetic group in vivo. AcpH is found only in Gram-negative organisms suggesting that it plays a role in some aspect of lipid metabolism that is unique to these organisms. The most obvious of which is biosynthesis of lipid A. Because AcpH is a hydrolase, it could possibly be an editing enzyme that intercepts acyl-ACPs that would give an inappropriate lipid A structure if used as acyl donors [
].
VirB8 is a bacterial virulence protein with cytoplasmic, transmembrane, and periplasmic regions. It is thought that it is a primary constituent of a DNA transporter. The periplasmic region interacts with VirB9, VirB10, and itself []. It is required for stabilisation of VirB3 (an inner membrane protein) []. This family also includes the conjugal transfer protein family TrbF, a family of proteins known to be involved in conjugal transfer. The TrbF protein is thought to compose part of the pilus required for transfer []. This entry represent a protein fold, which is similar to that of the NTF2-like family [
].
TrbF is known to be involved in conjugal transfer. It is thought to compose part of the pilus required for transfer [
]. This domain is similar to the type IV secretion system (T4ASS) component VirB8 and possibly has a similar fold to the nuclear transport factor-2 (NTF-2)-like superfamily [].
This entry represent penicillin-binding protein activators LpoA. It has been suggested that penicillin-binding protein activator acts as a regulator of peptidoglycan synthesis that is essential for the function of penicillin-binding protein 1A (PBP1a).
Protonated ethanolamine does not enter cells, while uncharged ethanolamine diffuses freely across the membrane. External concentrations of the two forms vary with the pH. It has been shown in Salmonella enterica that EutH is a membrane protein that facilitates diffusion of protonated ethanolamine [
]. It is involved in bacterial survival and replication in acidified macrophage vacuoles [].
The LanC-like protein superfamily encompasses a highly divergent group of peptide-modifying enzymes, including the eukaryotic and bacterial lanthionine synthetase C-like proteins (LanC) [
,
,
]; subtilin biosynthesis protein SpaC from Bacillus subtilis [,
]; epidermin biosynthesis protein EpiC from Staphylococcus epidermidis []; nisin biosynthesis protein NisC from Lactococcus lactis [,
,
]; GCR2 from Arabidopsis thaliana []; and many others. The 3D structure of the lantibiotic cyclase from L. lactis has been determined by X-ray crystallography to 2.5A resolution [
]. The globular structure is characterised by an all-α fold, in which an outer ring of helices envelops an inner toroid composed of 7 shorter, hydrophobic helices. This 7-fold hydrophobic periodicity has led several authors to claim various members of the family, including eukaryotic LanC-1 and GCR2, to be novel G protein-coupled receptors [
,
]; some of these claims have since been corrected [,
,
]. The EpiC protein from S. epidermidis, a hydrophobic but nevertheless soluble protein, is involved in the biosynthesis of the lantibiotic epidermin [
,
]. Its molecular structure is stabilised by a number of intramolecular disulphide bridges; the cysteine residues within its WCYG and CHG motifs, highly conserved in LanC-like proteins [], lie on 2 of the inner helices.
YggL from E.coli was recently characterised and it interacts with ribosome subunits 50S and 70S. It is a 50S-binding protein likely to be involved in particle assembly. It is a small protein extremely conserved in Gammaproteobacteria but also present in orders Burkholderiales and Neisseriales from Betaproteobacteria [
].
This entry represents archaeal 30S subunit ribosomal protein S12. With S4 and S5, S12 plays an important role in translational accuracy. It is located at the interface of the 30S and 50S subunits.
This entry represents the bacterial heat shock protein HspQ family. They are involved in the degradation of certain denaturated proteins, including DnaA, during heat shock stress.The crystal structure of HspQ from Escherichia coli showed a trimeric structure stabilized by a large and hydrophobic interaction surface [
].
Members of this family seem to be found mainly in Halobacteria. The function of this family is unknown. This protein is probably a replication protein due to conservation of functional motifs.
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 L21E family contains proteins from a number of eukaryotic
and archaebacterial organisms which include mammalian L2, Entamoeba histolytica L21, Caenorhabditis elegans L21 (C14B9.7), Saccharomyces cerevisiae (Baker's yeast) L21E (URP1) and Haloarcula marismortui HL31.This entry represents the archaeal 50S ribosomal L21e family of proteins.
MreC (murein formation C) is involved in the rod shape determination in Escherichia coli, and more generally in cell shape determination of bacteria whether or not they are rod-shaped [
].
Telomeres are specialised protein-DNA complexes that compose the ends of eukaryotic chromosomes. Telomeres protect chromosome termini from degradation and recombination and act together with telomerase to ensure complete genome replication. TEBP beta forms a complex with TEBP alpha and this complex is able to recognise and bind ssDNA to form a sequence-specific, telomeric nucleoprotein complex that caps the very 3' ends of chromosomes [].This entry represents Telomere-binding protein subunit beta (TEBB, also known as TEBP beta), mainly found in the eukaryotic taxon Oxytrichidae.
This family includes bacterial proteins including the probable inner membrane protein YgfX from Escherichia coli (formerly known as CptA). This had been thought to be a toxin, but it has no effect on cell growth [
]. It has been shown to interact with the cytoskeletal proteins FtsZ and MreB and to inhibit FtsZ GTP-dependent and MreB ATP-dependent polymerization []. In Serratia strains deficient in sdhE-ygfX, YgfX restores production of the antibiotic prodigiosin [].
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.
cotJA is part of the cotJ operon, which encodes spore coat proteins. Interaction of CotJA with CotJC is required for the assembly of both CotJA and CotJC into the spore coat [].
This entry represents a group of IWS1 plant homologues, including AtIWS1/2 from Arabidopsis. AtIWS1, also known as HNI9, is an evolutionary conserved component of the RNA polymerase II complex. It plays a role in N signaling by regulating several hundred N-responsive genes in roots [
]. It interacts with transcription factor BES1 and is involved in plant steroid hormone brassinosteroid regulated gene expression [].
The CRISPR-Cas system is a prokaryotic defense mechanism against foreign genetic elements. The key elements of this defense system are the Cas proteins and the CRISPR RNA. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are a family of DNA direct repeats separated by regularly sized non-repetitive spacer sequences that are found in most bacterial and archaeal genomes [
]. CRISPRs appear to provide acquired resistance against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA).The defense reaction is divided into three stages. In the adaptation stage, the invader DNA is cleaved, and a piece of it is selected to be integrated as a new spacer into the CRISPR locus, where it is stored as an identity tag for future attacks by this invader. During the second stage (the expression stage), the CRISPR RNA (pre-crRNA) is transcribed and subsequently processed into the mature crRNAs. In the third stage (the interference stage), Cas proteins, together with crRNAs, identify and degrade the invader [
,
,
].The CRISPR-Cas systems have been sorted into three major classes. In CRISPR-Cas types I and III, the mature crRNA is generally generated by a member of the Cas6 protein family. Whereas in system III the Cas6 protein acts alone, in some class I systems it is part of a complex of Cas proteins known as Cascade (CRISPR-associated complex for antiviral defense). The Cas6 protein is an endoribonuclease necessary for crRNA production whereas the additional Cas proteins that form the Cascade complex are needed for crRNA stability []. Cas6 is a member of the RAMP (repeat-associated mysterious protein) superfamily [
]. It is among the most widely distributed Cas proteins and is found in both bacteria and archaea []. Cas6 functions in the generation of CRISPR-derived guide RNAs for invader defense in prokaryotes []. The structure of this protein showed it adopts a tandem ferredoxin/RRM fold [].This entry represents a domain found in some CRISPR-associated proteins Cas6 and in uncharacterised proteins.
Members of this rare protein family regularly occur next to a member of the MXAN_0977 subfamily (
) of the di-heme cytochrome c peroxidase/MauG family (
). MauG itself (
) is a protein modification enzyme responsible for the tryptophan tryptophylquinone (TTQ) modification involved in methylamine dehydrogenase activation. All members of this family have a motif of four spaced invariant Cys residues.
These heat shock proteins (Hsp9 and Hsp12) are strongly expressed and undergo an increase of 100 fold, upon entry into stationary phase in yeast [
,
].
This entry represents a group of uncharacterised proteins. Though their function is not known, proteins in this family have been show to be secreted [
].
This entry represents coiled-coil domain of ASY3 and PAIR3.This entry represents a group of plant meiosis-specific proteins, such as AtASY3 from Arabidopsis and PAIR3 from rice. They are coiled-coil domain proteins required for normal meiosis [
]. PAIR3 is an axial element and part of the synaptonemal complex (SC) that forms between homologous chromosomes during meiosis []. Members of this family are homologues of SYCP2 from vertebrates and fungal Red1/Red10 [].
This entry represents a group of plant BRCA1 C terminus (BRCT) domain-containing proteins, including At4g02110 from Arabidopsis. Their function is not clear.
LIKE HETEROCHROMATIN PROTEIN1 (LHP1) is a polycomb repressive complex1 subunit required for epigenetic silencing of FLOWERING LOCUS C (FLC), which encodes a repressor of flowering [
]. It also interacts with LIF2, which is a heterogeneous nuclear ribonucleoprotein involved in Arabidopsis thaliana cell fate and stress responses [].
Diphthamide is a unique post-translationally modified histidine residue found only in translation elongation factor 2 (eEF-2). It is conserved from archaea to humans and serves as the target for diphteria toxin and Pseudomonas exotoxin A. These two toxins catalyse the transfer of ADP-ribose to diphtamide on eEF-2, thus inactivating eEF-2, halting cellular protein synthesis, and causing cell death [
]. The biosynthesis of diphtamide is dependent on at least five proteins, DPH1 to -5, and a still unidentified amidating enzyme. DPH3 and DPH4 share a conserved region, which encode a putative zinc finger, the DPH-type or CSL-type (after the the final conserved cysteine of the zinc finger and the next two residues) MB domain contains a Cys-X-Cys...Cys-X2-Cys motif which tetrahedrically coordinates both Fe and Zn. The Fe containing DPH-type MBD has an electron transfer activity [,
,
,
,
,
].This entry includes DPH3, DPH4 and their homologues.
Covalent DNA-protein crosslinks (DPCs) are toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription. Spartan (SPRTN) is a DNA-dependent metalloprotease which cleaves DPCs and plays a key role in maintaining genomic integrity [
]. SPRTN consists of an N-terminal SprT domain (responsible for the proteolytic cleavage of DPCs) followed by a basic region (BR, a DNA-binding element), both contributing to DNA binding. The C-terminal motifs and domains interact with proliferating cell nuclear antigen (PCNA) and ubiquitin, which collectively recruit SPRTN and the associated ATPase p97 or valosin-containing protein (p97 or VCP) to sites of DNA damage. The structure of the human SPRTN revealed a Zn2-binding sub-domain (ZBD) in SprT domain that shields its active site located in the metalloprotease sub-domain (MPD). The ZBD contains an ssDNA-binding site, with a DNA-base-binding pocket formed by aromatic residues and is thought to contribute to the ssDNA specificity of SPRTN, restricts the access of globular substrates, and positions DPCs, which may need to be partially unfolded, for optimal cleavage []. The proteolytic activity of SPRTN is regulated by various mechanisms. To prevent the recruitment of SPRTN to chromatin, SPRTN undergoes monoubiquitylation, which can then be deubiquitylated by an unknown ubiquitin protease triggered by DPC induction. Once SPRTN is recruited to chromatin, DNA binding stimulates its protease activity. It has been shown that SPRTN is uniquely activated by single-stranded DNA (ssDNA). Moreover, SPRTN can degrade itself, which may switch off its proteolytic function when repair is complete [
].SPRTN is also an activator of CHK1 (checkpoint kinase 1) during normal DNA replication by mediating proteolytic cleavage of CHK1, thereby promoting CHK1 removal from chromatin and subsequent activation. CHK1 phosphorylate SPRTN at the C-terminal regulatory domain and induces SPRTN recruitment to chromatin promoting DNA replication fork progression and DPC repair [
].In humans mutations of SPRTN are linked to human Ruijs-Aalfs syndrome (RJALS), a syndrome characterised by is characterised by genomic instability, premature aging, and hepatocellular carcinoma [
]. In mice, loss of SPRTN is embryonically lethal, and conditional inactivation of SPRTN in murine embryonic fibroblasts (MEFs) blocks cell proliferation [].
This entry includes TTC27 (Tetratricopeptide repeat protein 27) from animals, C19B12.01 from S. pombe and Emw1 (essential for maintenance of the cell wall protein 1) from Saccharomyces cerevisiae. Emw1 is required for the maintenance of the cell wall integrity [
].
This entry represents a group of thiol:disulfide interchange proteins, including TxlA from Cyanobacteria and HCF164 from Arabidopsis. HCF164 is a membrane-anchored thioredoxin-like protein that acts as a transducer of reducing equivalents in the thylakoid lumen. It contains a membrane-spanning sequence and a thioredoxin-like CXXC motif in the N- and C-terminal regions, respectively. The hcf164 mutant was found to be impaired in the stable assembly of the cytochrome b6 f complex within thylakoid membrane [
].
Protein LHCP TRANSLOCATION DEFECT (LTD, also known as GDC1) is a chloroplast protein that interacts with both proteins from the signal recognition particle (SRP) pathway and the inner chloroplast envelope [
]. It is required for chloroplast grana formation in Arabidopsis [].
Rhodanese-like domain-containing protein STR4-like
Type:
Family
Description:
This entry represents a group of rhodanese-like domain-containing proteins from plants and bacteria, including AtStr4 from Arabidopsis.
AtStr4 (also known as TROL, thylakoid rhodanese-like protein) is a nuclear-encoded component of thylakoid membranes that is required for tethering of FNR (ferredoxin-NADP(+) oxidoreductase) and sustaining efficient linear electron flow (LEF) in vascular plants [].
This protein is predicted to have 10 transmembrane regions. Members of this family are found so far in the Archaea (Archaeoglobus fulgidus and Pyrococcus horikoshii) and in a bacterial thermophile, Thermotoga maritima. In Pyrococcus, the gene is located between nadA and nadB, two components of an enzyme involved in de novo synthesis of NAD. By PSI-BLAST, this family shows similarity (but not necessarily homology) to gluconate permease and other transport proteins.
This entry includes the putative antitoxin RelB4 from Methanocaldococcus jannaschii (UniProt: Q58572). Most of the members in this entry are uncharacterised.
This entry represents a group of C2H2 transcription factors, including GIS, ZFP8 and GIS2 from Arabidopsis. They play partially redundant and essential roles in inflorescence trichome initiation and in its regulation by GA and cytokinins [,
].
This entry represents a group of plant RING zinc-finger domain proteins, including ATL67/ATL68/ATL69/ATL7070 from Arabidopsis. They belong to the ATL family of ubiquitin ligases [
]. Arabidopsis ATL consists of 91 members that contain the RING-H2 variation and a hydrophobic domain located at the N-terminal end [].
This family represents the periodic tryptophan protein 1 (PWP1), a chromatin-associated factor that regulates transcription during developmental growth as part of the TORC1 and Myc signaling pathway in response to nutrients. It regulates Pol I-mediated rRNA biogenesis and the epigenetic status of rDNA [
]. Drosophila melanogaster PWP1, also known as Protein no child left behind (nclb), is required in males for both germline stem cell (GSC) maintenance and early stages of germ cell differentiation of germ cell cysts []. In females it is necessary to regulate germ cell differentiation and egg chamber development [].
This entry represents a group of plant Armadillo (Arm) repeat proteins, including ABAP1/ARIA from Arabidopsis. ARIA interacts with a transcriptional regulator of abscisic acid-responsive gene expression [
]. ABAP1 is involved in a negative feedback loop regulating mitotic DNA replication during leaf development [].
This entry represents Vp10 protein from Seadornavirus. It is around 240 residues in length. Vp10 forms the virion spike "foot"and helps anchor the Vp9 spike "head"protein in the virion [
].
This is a bacterial family of cytoplasmic membrane proteins. It includes two transmembrane regions. The molecular function of FxsA is unknown, but in Escherichia coli its overexpression has been shown to alleviate the exclusion of phage T7 in those cells with an F plasmid.
The proteins in this entry are functionally uncharacterised, but the majority contain a sugar isomerase (SIS) domain, which is a phosphosugar-binding module found in proteins that have a role in phosphosugar isomerisation or regulation.
The proteins in this entry are functionally uncharacterised, but contain a single endonuclease/exonuclease/phosphatase domain. The family is represented by YafD, which has been reported to be similar to YadD, YjiP, YjiQ and YhgA, [
], though these are not found in this entry.
