This entry represents both L15 and L18e ribosomal proteins, which share a common structure consisting mainly of parallel beta sheets (beta-α-β units) with a core of three turns of irregular (β-β-alpha)n superhelix [
,
]. This family includes higher eukaryotic ribosomal 60S L27A, prokaryotic 50S L15, fungal mitochondrial L10, plant L27A, mitochondrial L15, chloroplast L18-3 proteins, 60S L18 from eukaryotes and 50S L18e from Archaea.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 [
,
].
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 [
,
].S14 is one of the proteins from the small ribosomal subunit.
In Escherichia coli, S14 is known to be required for the assembly of 30S particlesand may also be responsible for determining the conformation of 16S rRNA at the A site.
It belongs to a family of ribosomal proteins [] thatinclude bacterial, algal and plant chloroplast S14, yeast mitochondrial MRP2, cyanelle S14, archaebacteria Methanococcus vannielii S14, as well as yeast mitochondrial MRP2, yeast YS29A/B, and mammalian S29.
This entry represents Sm-like protein Lsm7. It could be found in the nuclear Lsm2-8 complex or in the cytoplasmic Lsm1-7 complex. The Lsm2-8 complex associates with multiple snRNP complexes containing the U6 snRNA (U4/U6 snRNP, U4/U6.U5 snRNP, and free U6 snRNP). It binds and stabilizes the 3'-terminal poly(U) tract of U6 snRNA and facilitates the assembly of U4-U6 di-snRNP and U4-U6-U5 tri-snRNP [
,
,
]. The Lsm1-7 complex associates with deadenylated mRNA and promotes decapping in the 5'-3' mRNA decay pathway [,
]. The Sm and the Lsm proteins, characterised by the Sm-domain, have RNA-related functions. The Sm heptamer ring associates with four (U1, U2, U4, U5) snRNPs, while Lsm2-8 heptamer is part of the U6 snRNP. Another Lsm heptameric complex, Lsm1-7, which differs from Lsm2-8 by one Lsm protein, functions in mRNA decapping, a crucial step in the mRNA degradation pathway [
].
Utp23 share homology with PINc domain protein Fcf1. They are components of the small subunit processome (SSU) that are involved in rRNA-processing and ribosome biogenesis [
,
]. Depletion of yeast Fcf1 and Fcf2 leads to a decrease in synthesis of the 18S rRNA and results in a deficit in 40S ribosomal subunits [
].
Serine/threonine-specific protein phosphatase/bis(5-nucleosyl)-tetraphosphatase
Type:
Domain
Description:
Protein phosphorylation plays a central role in the regulation of cell functions [
], causing the activation or inhibition of many enzymes involved in various biochemical pathways [
]. Kinases and phosphatases are the enzymes responsible for this, and may themselves be subject to control through the action of hormones and growth factors [
]. Serine/threonine(S/T) phosphatases (
) catalyse the dephosphorylation of phosphoserine and phosphothreonine residues. In
mammalian tissues four different types of PP have been identified and are known as PP1, PP2A, PP2B and PP2C. Except for PP2C, these enzymes are evolutionary related. The catalytic regions of the proteins are
well conserved and have a slow mutation rate, suggesting that major changes in these regions are highly detrimental [
].Protein phosphatase-1 (PP1) and protein phosphatase-2A (PP2A) have a broad
specificity and there are two closely related isoforms of each, alpha and beta. PP2A is a trimeric enzyme that consists of a core composed of a catalytic subunit associated with a 65kDa regulatory subunit and a
third variable subunit. Protein phosphatase-2B (PP2B or calcineurin), a calcium-dependent enzyme whose activity is stimulated by calmodulin, is composed of two subunits the catalytic A-subunit and the
calcium-binding B-subunit. The specificity of PP2B is restricted. Other serine/threonine specific protein phosphatases that have been characterised include mammalian phosphatase-X (PP-X), and Drosophila
phosphatase-V (PP-V), which are closely related but yet distinct from PP2A; yeast phosphatase PPH3, which is similar to PP2A, but with different enzymatic properties; and Drosophila phosphatase-Y (PP-Y), and yeast
phosphatases Z1 and Z2 which are closely related but yet distinct from PP1.
This entry represents conserved transmembrane proteins that in humans are expressed from a region upstream of the FragileXF site and appear to be intimately linked with Fragile-X syndrome. The absence of the human TMEM185A protein does not necessarily lead to developmental delay, but might, in combination with other, currently unknown, factors. Alternatively, the TMEM185A protein is either redundant, or its function can be complemented by the highly similar chromosome 2 retro-pseudogene product, TMEM185B [
].
Ribosomal protein S15 is one of the proteins from the small ribosomal subunit. In Escherichia coli, this protein binds
to 16S ribosomal RNA and functions at early steps in ribosome assembly. It belongs to a family of ribosomal proteinswhich, on the basis of sequence similarities [
,], groups bacterial and plant chloroplast S15;archaeal Haloarcula marismortui HmaS15 (HS11); yeast mitochondrial S28; and mammalian, yeast, Brugia pahangi
and Wuchereria bancrofti S13. S15 is a protein of 80 to 250 amino-acid residues.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 [
,
].
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 contains 30S ribosomal protein S15P/S13e and 40S ribosomal protein S13, which belong to the S15P family.
Macroautophagy is a bulk degradation process induced by starvation in eukaryotic cells. In yeast, 15 Atg proteins coordinate the formation of autophagosomes. The pre-autophagosomal structure contains at least five Atg proteins: Atg1p, Atg2p, Atg5p, Aut7p/Atg8p and Atg16p, found in the vacuole [
,
]. The C-terminal glycine of Atg12p is conjugated to a lysine residue of Atg5p via an isopeptide bond. During autophagy, cytoplasmic components are enclosed in autophagosomes and delivered to lysosomes/vacuoles. Autophagy protein 16 (Atg16) has been shown to bind to Atg5 and is required for the function of the Atg12p-Atg5p conjugate []. Autophagy protein 5 (Atg5) is directly required for the import of aminopeptidase I via the cytoplasm-to-vacuole targeting pathway [].This entry represents autophagy protein 5 (Atg5).
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 [
,
].A number of eukaryotic and archaebacterial ribosomal proteins can be grouped in this family of ribosomal proteins, S17e (RPS17e). They include, vertebrate, Drosophila and Neurospora crassa (crp-3) S17's as well as yeast S17a (RP51A) and S17b (RP51B) and archaebacterial S17e [
,
,
].
This entry represents the palmitoyl protein thioesterase family. Its members include palmitoyl-protein thioesterase 1 and lysosomal thioesterase 2 (PPT1 and PPT2). PPT1 is responsible for the removal of a palmitate group from its substrate proteins, which may include presynaptic proteins like SNAP-25, cysteine string protein (CSP), dynamin, and synaptotagmin [
]. PPT2 removes thioester-linked fatty acyl groups from various substrates including S-palmitoyl-CoA []. PPT1 and -2 perform non-redundant roles in lysosomal thioester catabolism [].Mutations in the PPT1 gene cause infantile-onset neuronal ceroid lipofuscinosis (INCL), which is a severe pediatric neurodegenerative disorder [
].This entry also includes uncharacterised proteins from fungi and plants.
This family includes mitochondrial protein C2orf69 from human, previously known as UPF0565, which is an important regulator of human mitochondrial function and may play a role in the respiratory chain and other metabolic pathways [
].
This entry represents ribosomal protein L19 from eukaryotes, as well as L19e from archaea [
]. L19/L19e is part of the large ribosomal subunit, whose structure has been determined in a number of eukaryotic and archaeal species [].
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 L2 is one of the proteins from the large ribosomal subunit. The best conserved region is located in the C-terminal section of these proteins. In Escherichia coli, L2 is known to bind to the 23S rRNA and to have peptidyltransferase activity. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities [
], groups:Eubacterial L2.Algal and plant chloroplast L2.Cyanelle L2.Archaebacterial L2.Plant L2.Slime mold L2.Marchantia polymorpha mitochondrial L2.Paramecium tetraurelia mitochondrial L2.Fission yeast K5, K37 and KD4.Yeast YL6.Vertebrate L8.
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 [
,
].A number of eukaryotic ribosomal proteins can be grouped on the basis of sequence similarities [
].One of these families consists of Xenopus S8, and mammalian, insect and yeast S7. These proteins have about
200 amino acids.
This is the GASA gibberellin regulated cysteine rich protein (GRPs) family. The expression of these proteins is up-regulated by the plant hormone gibberellin, most of these proteins have a role in plant development and some of its members have antimicrobial activity [
,
]. There are 12 cysteine residues conserved within the alignment giving the potential for these proteins to possess 6 disulphide bonds.Included in this family are some GRPs found in fruits and pollens that have been identified as allergens, including peach Pru p 7, Japanese apricot Pru m 7, orange Cit s 7, pomegranate Pun g 7, and cypress pollen GRP [
,
,
].
Vesicle-associated membrane-protein-associated protein
Type:
Family
Description:
This entry represents a family of vesicle-associated membrane-protein-associated proteins (VAPs) and plant VAP homologs (PVAPs) [
]. VAPs (VAPA and VAPB in humans, VAPA, VAPB and VAPC in other mammals []) are endoplasmic reticulum (ER) proteins that play roles in vesicle trafficking, neurotransmitter release, microtubule organisation, lipid transport and unfolded protein response []. VAP proteins contain an MSP domain in their N-terminal half, which has been shown to interact with proteins containing a FFAT motif, such as members of the oxysterol-binding protein (OSBP) family or the phosphatidylinositol transfer proteins from the PITPNM family []. Yeast VAP homologues are known as Scs2 and Scs22 [].
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 is for the ribosomal protein S30.
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 [
,
].A number of eukaryotic ribosomal proteins can be grouped on the basis of sequence similarities. The small ribosomal subunit protein S12 contains 130-150 amino acid residues, and is thought to be involved in the translation initiation step. This family consists of eukaryotic S12 ribosomal proteins, including those from vertebrates [
], Trypanosoma brucei [], Caenorhabditis elegans, Drosophila and Saccharomyces cerevisiae (Baker's yeast).
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 includes: Ribosomal L7A from metazoa, Ribosomal L8-A and L8-B from fungi, 30S ribosomal protein HS6 from archaebacteria, 40S ribosomal protein S12 from eukaryotes, ribosomal protein L30 from eukaryotes and archaebacteria, Gadd45 and MyD118 [
].
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 L19 is one of the proteins from the large ribosomal subunit [
,
]. In Escherichia coli, L19 is known to be located at the 30S-50S ribosomal subunit interface [] and may play a role in the structure and function of the aminoacyl-tRNA binding site. It belongs to a family of ribosomal proteins, including L19 from bacteria and the chloroplasts of red algae.
This superfamily represents the core domain of ribosomal proteins L37ae and L37e, which share a common rubredoxin-like metal-binding fold containing two CX(n)C motifs (where n is usually two) [
].
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 ribosomal protein is found in archaebacteria and eukaryotes [
]. Ribosomal protein L37 has a single zinc finger-like motif of the C2-C2 type [].
This superfamily represents a rubredoxin-like metal-binding fold found in ribosomal proteins L37ae, L37e, L44e and S27e. This domain contains two CX(n)C motifs (where n is usually two) [
,
].
This entry represents the initiator of plasmid replication proteins, including RepA and related sequences. RepA is a protein from Escherichia coli involved in plasmid replication. The RepA protein binds to DNA repeats that flank the repA gene [
,
]. A similar RepA family of proteins with wider distribution are the bacterial plasmid DNA replication initiator proteins (see ).
Bacteria synthesise a set of small, usually basic proteins of about 90 residues that bind DNA and are known as histone-like proteins [
,
]. Examples include the HU protein in Escherichia coli which is a dimer of closely related alpha and beta chains and in other bacteria can be a dimer of identical chains. HU-type proteins have been found in a variety of eubacteria, cyanobacteria and archaebacteria, and are also encoded in the chloroplast genome of some algae []. The integration host factor (IHF), a dimer of closely related chains which seem to function in genetic recombination as well as in translational and transcriptional control [] is found in enterobacteria and viral proteins include the African Swine fever virus protein Pret-047 (also known as A104R or LMW5-AR) [].The exact function of these proteins is not yet clear but they are capable of wrapping DNA and stabilising it from denaturation under extreme environmental conditions. The structure is known for one of these proteins [
]. The protein exists as a dimer and two "β-arms"function as the non-specific binding site for bacterial DNA.
Bacterial high affinity transport systems are involved in active transport of solutes across the cytoplasmic membrane. Most of the bacterial ABC (ATP-binding cassette) importers are composed of one or two transmembrane permease proteins, one or two nucleotide-binding proteins and a highly specific periplasmic solute-binding protein. In Gram-negative bacteria the solute-binding proteins are dissolved in the periplasm, while in archaea and Gram-positive bacteria, their solute-binding proteins are membrane-anchored lipoproteins [
,
]. On the basis of sequence similarities, the vast majority of these solute-binding proteins can be grouped into eight family clusters [
], which generally correlate with the nature of the solute bound. This entry represents the family 2 [,
]. Family 2 members include:Autoinducer 2-binding protein LsrB from E. coli and Salmonella typhimurium [
,
]
D-galactose-binding periplasmic proteinAutoinducer 2-binding periplasmic protein LuxPD-ribose-binding periplasmic proteinMultiple sugar-binding periplasmic receptor ChvEThis entry represents a domain found in a variety of bacterial periplasmic binding proteins belonging mainly to family 2 which can recognise fructose [
].
The Escherichia coli acrA and acrB genes encode a multi-drug efflux system that is believed to protect the bacterium against hydrophobic inhibitors [
]. The E. coli AcrB protein is a transporter that is energized by proton-motive force and that shows the widest substrate specificity among all known multidrug pumps, ranging from most of the currently used antibiotics, disinfectants, dyes, and detergents to simple solvents.The structure of ligand-free AcrB shows that it is a homotrimer of 110kDa per subunit. Each subunit contains 12 transmembrane helices and two large
periplasmic domains (each exceeding 300 residues) between helices 1 and 2, and helices 7 and 8. X-ray analysis of the overexpressed AcrB protein demonstrated that the three periplasmic domains form, in the centre, a funnel-like structure and a connected narrow (or closed) pore. The pore is opened to the periplasm through three vestibules located at subunit interfaces. These vestibules were proposed to allow direct access of drugs from the periplasm as well as the outer leaflet of the cytoplasmic membrane. The three transmembrane domains of AcrB protomers form a large, 30A-wide central cavity that spans the cytoplasmic membrane and extends to the cytoplasm X-ray crystallographic structures of the trimeric AcrB pump from E. coli with four structurally diverse ligands demonstrated that three molecules of ligand bind simultaneously to the extremely large central cavity of 5000 cubic angstroms, primarily by hydrophobic, aromatic stacking and van der Waals interactions. Each ligand uses a slightly different subset of AcrB residues for binding. The bound ligand molecules often interact with each other, stabilising the binding.
This family has a novel fold known as a spiral β-roll, consisting of a 15-stranded beta sheet wrapped around a single alpha helix. It forms dimers. It has some structural similarity to the E. coli lipoprotein localisation factors LolA (
) and LolB (
). Its structure suggests that it may have a role in glycolipid binding. Its genomic context supports a role in glycolipid metabolism [].
AriR, also known as YmgB, is part of the three gene cluster ymgABC which has a role in biofilm development and stability. YmgB represses biofilm formation in rich medium containing glucose, decreases cellular motility and also protects the cell from acid, which indicates that YmgB has an important function in acid-resistance [
]. YmgB binds as a dimer to genes which are important for biofilm formation via a ligand. Due to its important function in acid resistance it is also known as AriR (regulator of acid resistance influenced by indole) []. AriR may be a non-specific DNA-binding protein that binds genes and/or intergenic regions via a geometric recognition.
Members of this family are integral membrane proteins [
], and many are implicated in the productionof polysaccharide. The family includes RfbX part of the O antigen biosynthesis
operon [], and SpoVB from Bacillus subtilis (),
which is involved in spore cortex biosynthesis [].
This group belongs to the ferritin domain superfamily and has the ferritin-like structural fold. Ferritins constitute a broad superfamily of iron storage proteins, widespread in all domains of life [
,
]. Ferritins and bacterioferritins have essentially the same architecture, assembling in a 24mer cluster to form a hollow, roughly spherical, construction. This consists of a mineral core of hydrated ferric oxide and a multi-subunit protein shell, which encloses the former and assures its solubility in an aqueous environment. Due to the absence of the C-terminal fifth helix of 24mer ferritins, members of the Dps group assemble only to dodecameric protein shells [].Members of this entry were originally discovered as stress proteins, which protect DNA against oxidative stress during nutrient starvation [
], hence the name Dps (DNA protection during starvation protein). Several members of the group, such as Dps from Escherichia coli or the Dps homologue from Bacillus subtilis, exhibit a DNA-binding activity that is at least partially linked with iron complexation []. DNA binding by these proteins was shown to suffice for protection against oxidative DNA damage and might be mediated by magnesium ions, which bridge the protein surfaces with the polyanionic DNA [,
]. Functionally, this group is much more diverse, with many members promoting iron incorporation, while others act as immunogens, neutrophil activators [], cold-shock proteins, or constituents of fine-tangled pili []. Another mode of protection against reactive oxygen species implies the preferential consumption of hydrogen peroxide instead of oxygen during biomineralization [].For additional information please see [
,
].
This domain contains a helix-turn-helix motif [
].Every member of this family is N-terminal to a SIS domain
. Members of this family are probably regulators of genes
involved in phosphosugar metobolism.
Members of this family are substrate-binding periplasmic proteins of ABC transporters. This subfamily includes SsuA, a member of a transporter operon needed to obtain sulphur from aliphatic sulphonates. Related proteins include taurine (NH2-CH2-CH2-S03H) binding proteins, the probable sulphate ester binding protein AtsR, and the probable aromatic sulphonate binding protein AsfC. All these families make sulphur available when Cys and sulphate levels are low [
].
Baseplate protein Ggp exists as an homotrimer and forms a hub-like structure with an inner diameter of 25 Angstroms through which DNA can presumably pass during infection [
].
This entry contains a family of small hydrophobic holin proteins with one or more transmembrane domains. Members of this family fall into the holin superfamily II, and Phage 21 S holin is the prototype for this superfamily. It has two transmembrane segments with both the N- and C-termini on the cytoplasmic side of the inner membrane in E. coli. Holins are a diverse family of proteins that cause bacterial membrane lysis during late-protein synthesis. It is thought that the temporal precision of holin-mediated lysis may occur through the build up of a holin oligomer which causes the lysis [
,
].
The histone-like nucleoid-structuring (H-NS) protein is a DNA-binding protein implicated in transcriptional repression (silencing) as well as in bacterial chromosome organisation [
]. H-NS binds tightly to AT-rich dsDNA, increases its thermal stability and inhibits transcription. It also binds to ssDNA and RNA but with a much lower affinity [].
The OapA domain gets its name from the Haemophilus influenzae protein OapA, which is required for the expression of colony opacity, thus opacity- associated protein A [
]. The OapA protein is required for efficient nasopharyngeal mucosal colonization, and its expression is associated with a distinctive transparent colony phenotype. OapA is thought to be a secreted protein, and its expression exhibits high-frequency phase variation []. The OapA protein contains a C-terminal OapA domain, which in the E. coli protein YtfB has been shown to bind to peptidoglycan []. A screen to identify factors that affect cell division in E. coli discovered that overproducing a fragment of YtfB, including its OapA domain, caused cells to grow as long filaments []. OapA domains are commonly associated with other domains that are involved in breaking peptidoglycan cross-links such as [
]. The OapA domain is distantly related to another peptidoglycan binding domain.
This entry represents a structural domain found in both the histidine-containing phosphocarrier protein HPr, as well as its structural homologues, which includes the catabolite repression protein Crh found in Bacillus subtilis [
,
]. This domain has a alpha+beta structure found in two layers with an overall architecture of an open faced β-sandwich in which a β-sheet is packed against three α-helices. The histidine-containing phosphocarrier protein (HPr) is a central component of the phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS), which transfers metabolic carbohydrates across the cell membrane in many bacterial species [
,
]. PTS catalyses the phosphorylation of incoming sugar substrates concomitant with their translocation across the cell membrane. The general mechanism of the PTS is as follows: a phosphoryl group from phosphoenolpyruvate (PEP) is transferred to Enzyme I (EI) of the PTS, which in turn transfers it to the phosphoryl carrier protein (HPr) [,
]. Phospho-HPr then transfers the phosphoryl group to a sugar-specific permease complex (enzymes EII/EIII). HPr [
,
] is a small cytoplasmic protein of 70 to 90 amino acid residues. In some bacteria, HPr is a domain in a larger protein that includes a EIII(Fru) (IIA) domain and in some cases also the EI domain. A conserved histidine in the N-terminal section of HPr serves as an acceptor for the phosphoryl group of EI. In the central part of HPr, there is a conserved serine which (in Gram-positive bacteria only) is phosphorylated by an ATP-dependent protein kinase; a process which probably play a regulatory role in sugar transport. Regulatory phosphorylation at the conserved Ser residue does not appear to induce large structural changes to the HPr domain, in particular in the region of the active site [
,
].
This entry represents SsrA-binding protein (aka small protein B or SmpB), which is a unique RNA-binding protein that is conserved throughout the bacterial kingdom and is an essential component of the SsrA quality-control system. Tight recognition of codon-anticodon pairings by the ribosome ensures the accuracy and fidelity of protein synthesis. In eubacteria, translational surveillance and ribosome rescue are performed by the 'tmRNA-SmpB' system (transfer messenger RNA-small protein B). SmpB binds specifically to the ssrA RNA (tmRNA) and is required for stable association of ssrA with ribosomes. SsrA RNA recognises ribosomes stalled on defective messages and acts to mediate the addition of a short peptide tag to the C terminus of the partially synthesised nascent polypeptide chain. Within a stalled ribosome, SmpB interacts with the three universally conserved bases G530, A1492 and A1493 that form the 30S subunit decoding centre, in which canonical codon-anticodon pairing occurs [
]. The SsrA-tagged protein is then degraded by C-terminal-specific proteases. Formation of an SmpB-SsrA complex appears to be critical in mediating SsrA activity after aminoacylation with alanine but prior to the transpeptidation reaction that couples this alanine to the nascent chain []. The SmpB protein has functional and structural similarities with initiation factor 1, and is proposed to be a functional mimic of the pairing between a codon and an anticodon. The core of SmpB consists of an antiparallel β-barrel containing eight β-strands and three helices [
].
The Factor for Inversion Stimulation (FIS) protein is a regulator of
bacterial functions, and binds specifically to weakly related DNA sequences [
]. It activates ribosomal RNA transcription, and is involved in upstreamactivation of rRNA promoters. Found in gamma proteobacterial microbes, the
protein has been shown to play a part in the regulation of virulence factorsin both Salmonella typhimurium and Escherichia coli [
]. Some of itsfunctions include inhibition of the initiation of DNA replication from the
OriC site, and promotion of Hin-mediated DNA inversion [].In its C-terminal extremity, FIS encodes a helix-turn-helix (HTH) DNA-binding motif, which shares a high degree of similarity with other HTH
motifs of more primitive bacterial transcriptional regulators, such as thenitrogen assimilation regulatory proteins (NtrC) from species like Azobacter,
Rhodobacter and Rhizobium. This has led to speculation that both evolvedfrom a single common ancestor [
]. Recently, the crystal structure of wild-type E. coli FIS was
resolved, together with six mutants [] - the first crystal structure wassolved in 1991. From the most recent 2.0A structure [
] of wild-typeFIS, the protein was observed to exist as a homodimer in the bacterial
cytoplasm. By comparison with the structures of FIS mutants, it was deducedthat arginine-71 is critical for the binding of FIS to RNA polymerase, while
glycine-72 stabilises the tertiary structure.
MzrA modulates the activity of the EnvZ/OmpR two-component regulatory system, probably by directly modulating EnvZ enzymatic activity and increasing stability of phosphorylated OmpR [
,
]. EnvZ/OmpR mediates regulation of OmpF and OmpC, the two major pore-forming outer membrane proteins (OMPs).
This conserved region identifies a set of hypothetical protein sequences from the Metazoa and Ascomycota which include SHQ1 from Saccharomyces cerevisiae.
This entry represents the TMEM70/TMEM186/TMEM223 protein family. TMEM70 is a family of proteins essential for assembly of the mitochondrial proton-transporting ATP synthase complex within the inner mitochondrial membrane. TMEM70 functions in the assembly of complexes I and V [
].
Human MAP9 is involved in organisation of the mitotic spindle [
]. Besides being required for mitosis progression and cytokinesis, it may stabilise interphase microtubules []. Upon DNA damage, it is phosphorylated probably by ATM or ATR [].
Competence is the ability of a cell to take up exogenous DNA from its environment, resulting in transformation. It is widespread among bacteria and is probably an important mechanism for the horizontal transfer of genes. DNA usually becomes available by the death and lysis of other cells. Competent bacteria use components of extracellular filaments called type 4 pili to create pores in their membranes and pull DNA through the pores into the cytoplasm. This process, including the development of competence and the expression of the uptake machinery, is regulated in response to cell-cell signalling and/or nutritional conditions [
].The development of genetic competence in Bacillus subtilis is a highly regulated adaptive response to stationary-phase stress. For competence to develop, the transcriptional regulator, ComK, must be activated. ComK is required for the expression of genes encoding proteins that function in DNA uptake. In log-phase cultures, ComK is inactive in a complex with MecA and ClpC. The comS gene is induced in response to high culture cell density and nutritional stress and its product functions to release active ComK from the complex. ComK then stimulates the transcription initiation of its own gene as well as that of the late competence operons [
].The comE locus is obligatory for bacterial cell competence. comEA and comEC are required for transformability, whereas the products of comEB and of the overlapping comER, which is transcribed in the reverse direction, are dispensable [
].ComEA has been shown to be an integral membrane protein, as predicted from hydropathy analysis, with its C-terminal domain outside the cytoplasmic membrane. This C-terminal domain possesses a sequence with similarity to those of several proteins known to be involved in nucleic acid transactions including UvrC and a human protein that binds to the replication origin of the Epstein-Barr virus (strain GD1) (HHV-4) (Human herpesvirus 4) [
].
Competence is the ability of a cell to take up exogenous DNA from its environment, resulting in transformation. It is widespread among bacteria and is probably an important mechanism for the horizontal transfer of genes. DNA usually becomes available by the death and lysis of other cells. Competent bacteria use components of extracellular filaments called type 4 pili to create pores in their membranes and pull DNA through the pores into the cytoplasm. This process, including the development of competence and the expression of the uptake machinery, is regulated in response to cell-cell signalling and/or nutritional conditions [
].The development of genetic competence in Bacillus subtilis is a highly regulated adaptive response to stationary-phase stress. For competence to develop, the transcriptional regulator, ComK, must be activated. ComK is required for the expression of genes encoding proteins that function in DNA uptake. In log-phase cultures, ComK is inactive in a complex with MecA and ClpC. The comS gene is induced in response to high culture cell density and nutritional stress and its product functions to release active ComK from the complex. ComK then stimulates the transcription initiation of its own gene as well as that of the late competence operons [
].This is the DNA internalisation-related competence protein ComEC/Rec2 family. Apparent orthologs are found in 5 species so far (Haemophilus influenzae, Escherichia coli, Bacillus subtilis, Neisseria gonorrhoeae, Streptococcus pneumoniae), of which all but E. coli are model systems for the study of competence for natural transformation. This protein is a predicted multiple membrane-spanning protein likely to be involved in DNA internalisation.
Competence is the ability of a cell to take up exogenous DNA from its environment, resulting in transformation. It is widespread among bacteria and is probably an important mechanism for the horizontal transfer of genes. DNA usually becomes available by the death and lysis of other cells. Competent bacteria use components of extracellular filaments called type 4 pili to create pores in their membranes and pull DNA through the pores into the cytoplasm. This process, including the development of competence and the expression of the uptake machinery, is regulated in response to cell-cell signalling and/or nutritional conditions [
].This group represents a competence protein ComB.
Birt-Hogg-Dube' syndrome, a disorder characterised by benign tumours of the hair follicle, lung cysts and renal neoplasia, is caused by germline mutations in the BHD(FLCN) gene; this encodes a tumour suppressor protein, folliculin (FLCN), of unknown function [
]. The folliculin- interacting protein, FNIP1, has also been identified and shown to interact with 5' AMP-activated protein kinase (AMPK), which plays a vital role in energy sensing []. Together, then, it is thought that folliculin (mutated in Birt-Hogg-Dube' syndrome) and its interaction partner, FNIP1, may be involved in energy and/or nutrient sensing via the AMPK and mTOR signalling pathways.FNIP1 has a homologue, FNIP2, which also interacts with FLCN and AMPK. C-terminally-deleted FLCN mutants, like those produced by germline mutations in BHD patients, do not bind FNIP2, suggesting that FLCN tumour-suppressor function may be facilitated by interactions with both FNIP1 and FNIP2 via its C terminus [
]. FNIP1 and FNIP2 are able to form homo- or heteromeric multimers, and may hence function either independently or cooperatively with FLCN [].This entry represents the FNIP family, including FNIP1 and FNIP2.
During F plasmid conjugation, the SOS response is suppressed by PsiB, an F-plasmid-encoded protein that binds and sequesters free RecA to prevent filament formation. PsiB contains a central five-stranded anti-parallel beta sheet that is buttressed by alpha helices from the N and C termini. Its structure is similar to CapZ, a eukaryotic actin filament capping protein [
].
Uncharacterised protein C6orf15 (also known as STG) was initially isolated in rhesus monkey taste buds [
]. The human homologue is also expressed in skin and tonsils []. In mice, C6orf15 has been shown to be secreted into the extracellular matrix where it binds to a number of different extracellular matrix proteins [].
TMEM11 (also called PMI in Drosophila) regulates mitochondrial morphogenesis via a mechanism which is independent of mitofusins and dynamin-related protein 1 [
].
SIL (also called STIL/TAL1 interrupting locus) is an immediate-early gene that is essential for embryonic development and is implicated in T-cell leukemia-associated translocations [
,
]. Sil protein is necessary for proper mitotic spindle organisation in zebrafish and human cells and localizes to the mitotic spindle poles only during metaphase []. Mouse Sil was suggested to play a role as a positive regulator of the sonic hedgehog pathway, acting downstream of PTCH1 []. In human, cell cycle-dependent phosphorylation of Sil is required for its interaction with Pin1, a regulator of mitosis [].Primary microcephaly (MCPH) is an autosomal-recessive congenital disorder characterised by smaller-than-normal brain size and mental retardation. Three different homozygous mutations in SIL were identified in patients from three of the five families linked to the MCPH7 locus; all are predicted to truncate the Sil protein [
].
VGF protein is a neurosecretory protein originally
identified as a product of the nerve growth factor responsivegene Vgf in rat pheochromocytoma PC12 cells [
,
]. VGF may be involved in the regulation of cell-cell interactions or in synatogenesis during the maturation of the nervous system []. Neuroendocrine regulatory peptides (NERP)-1 and NERP-2 are bioactive peptides processed from VGF and involved in the control of body fluid homeostasis by regulating vasopressin release. Administration of NERPs suppresses hypertonic saline- or angiotensin II-induced vasopressin release from the hypothalamus and pituitary [
].
This entry represents the gamma-secretase-activating protein (GSAP) family, whose members include the mammalian GSAPs and the insect pigeon proteins (also known as linotte proteins). GSAP is a gamma-secretase regulator. It specifically activates the production of beta-amyloid protein through interactions with both gamma-secretase and its substrate, the amyloid precursor protein carboxy-terminal fragment (APP-CTF) [
]. This has led to interest in the protein as potential therapeutic target for the treatment of Alzheimer's disease []. Pigeon/linotte was initially identified as a gene that functions in adult Drosophila during associative learning [].
This family consists of SLAIN motif-containing proteins, including SLAIN1 and SLAIN2. SLAIN1 was named after the SLAIN amino acid stretch in its C terminus. It is expressed at the stem cell and epiblast stages of ESC differentiation and in the epiblast, nervous system, tailbud and somites of the developing embryo in mice [
]. SLAIN2 has been shown to bind to the plus end of microtubules and to regulate microtubule dynamics and organisation. It promotes cytoplasmic microtubule nucleation and elongation. It is required for normal structure of the microtubule cytoskeleton during interphase [].
This entry represents the sporulation protein YunB. In Bacillus subtilis its expression is controlled by sigmaE. The gene yunB seems to code for a protein involved, at least indirectly, in the pathway leading to the activation of sigmaK. Inactivation of yunB delays sigmaK activation and results in reduced sporulation efficiency [
].
This uncharacterised protein is one of a number of proteins conserved in all known endospore-forming Firmicutes (low-GC Gram-positive bacteria), including Carboxydothermus hydrogenoformans, and it is not found in non-endospore forming species. It is uniformly distributed in the mother
cell cytoplasm in Bacillus subtilis [].
The DNA primase DnaG of Escherichia coli and its apparent orthologs in other bacterial species are approximately 600 residues in length. Within this set, a conspicuous outlier in percent identity, as seen in a UPGMA difference tree, is the branch containing the Mycoplasmas. This lineage is also unique in containing the small, DNA primase-related protein found in this family, which is homologous to the central third of DNA primase. Several small regions of sequence similarity specifically to Mycoplasma sequences rather than to all DnaG homologues suggests that the divergence of this protein from DnaG post-dated the separation of bacterial lineages. The function of this DNA primase-related protein is unknown.
This entry includes budding yeast overproduction-induced pheromone-resistant yeast protein 1 (Opy1), which blocks the G1 arrest in the presence of mating pheromone [
].
This entry represents protein SCAI from metazoans and plants. SCAI is a transcriptional cofactor and tumour suppressor that suppresses MKL1-induced SRF transcriptional activity. It may function in the RHOA-DIAPH1 signal transduction pathway and regulate cell migration through transcriptional regulation of ITGB1 [].
This family describes essentially the full length of an uncharacterised protein from Bacillus subtilis (YqeW) and corresponding lengths of longer proteins from Escherichia coli and Treponema pallidum. There is homology to one other group of proteins, type II sodium/phosphate (Na/Pi) cotransporters. A well-conserved repeated domain in this family, approximately 60 residues in length, is also repeated in the Na/Pi cotransporters, although with greater spacing between the repeats. The two families share additional homology in the region after the first repeat, share the property of having extensive hydrophobic regions, and may be similar in function.
Members of this family of class III pyridoxal-phosphate-dependent aminotransferases are diaminobutyrate--2-oxoglutarate aminotransferase (
) that catalyze the first step in ectoine biosynthesis from L-aspartate beta-semialdehyde. This family is readily separated phylogenetically from enzymes with the same substrate and product but involved in other process such as siderophore (
) or 1,3-diaminopropane (
) biosynthesis. Ectoine is a compatible solute particularly effective in conferring salt tolerance.
The nucleocapsid protein is referred to as NP. NP is is the major
structural component of the nucleocapsid. The protein is approx.58kDa. 2600 NP molecules go to tightly encapsidate the viral RNA.
NP interacts with several other viral encoded proteins, all of which are involved in controlling replication: NP-NP, NP-P, NP-(PL),
and NP-V [,
,
].
This entry represents the fluorescence recovery protein (FRP), the structure of which has been solved for the cyanobacteria Synechocystis (PDBe:4JDQ).Cyanobacteria contain antenna complexes called phycobilisomes, which are quenched by orange carotenoid protein (OCP) under high light conditions. FRP causes the dissociation of OCP from the phycobilisomes by interacting with the C-terminal domain of OCP, accelerating the conversion of the active red OCP (OCPr) to the inactive orange form (OCPo). A patch of residues (W50, D54, H53, and R60) contributed by both chains of the FRP dimer cause the acceleration of the OCPr to OCPo conversion. Mutation of the absolutely conserved amino acid (R60) affects the activity of FRP [
].
Adrenocortical dysplasia protein (acd, also known as TPP1) is a component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways [
]. It also forms a heterodimer with POT1 that increases the activity and processivity of the telomerase core enzyme [].This entry also includes fission yeast TPP1 homologue, Tpz1. Together with Pot1 it forms a complex that protects telomeres and regulates telomere length [
].
This family consists of Bromovirus coat proteins. RNA-protein interactions stabilise many viruses and also the nucleoprotein cores of enveloped animal viruses (e.g. retroviruses). The nucleoprotein particles are frequently pleomorphic and generally unstable due to the lack of strong protein-protein interactions in their capsids.
The structure is known for Cowpea chlorotic mottle virus (CCMV) [
]. It shows novel quaternary structure interactions based on interwoven carboxyterminal polypeptides that extend from canonical capsid β-barrel subunits. Additional particle stability is provided by intercapsomere contacts between metal ion mediated carboxyl cages and by protein interactions with regions of ordered RNA.
This entry represents a small group of highly conserved proteins from bacteria, in particular Helicobacter species. The structure is a bundle of alpha helices. The function is not known.
The alpha-2-macroglobulin receptor-associated protein (RAP) is a intracellular glycoprotein that binds to the alpha-2-macroglobulin receptor (a2MR), also known as low-density lipoprotein receptor-related protein (LRP), and other members of the low density lipoprotein receptor family. The protein inhibits binding of all currently known ligands of these receptors [
,
,
].
Members of this bacterial protein family are small, at roughly 100 amino acids. The gene is almost invariably the downstream member of a gene pair. It is a predicted DNA-binding protein from a clade within the helix-turn-helix family
. These gene pairs, when found on the bacterial chromosome, are located often with prophage regions, but also both in integrated plasmid regions and in housekeeping gene regions. Analysis suggests that the gene pair may serve as an addiction module.
Mouse gametogenetin binding protein 2 (GGNBP2) was found to interact with gametogenetin protein 1 (GGN1), which is the product of a testicular germ cell-specific gene specifically expressed from late pachytene spermatocytes through round spermatids. Therefore, GGNBP2 was suggested to be involved in spermatogenesis [
].
Transcription factors containing basic-helix-loop-helix (bHLH) domains interact to regulate differentiation in a number of cellular systems, including myogenesis, neurogenesis and haematopoiesis [
]. The DNA-binding activity of these proteins is mediated via the basic region of the bHLH domain, and is dependent upon formation of homo- and/or heterodimers by these transcription factors.The Id family of proteins (whose members include Id1, Id2, Id3 and the Drosophila homologue emc) contain a HLH-dimerization domain but lack the DNA-binding basic region. Formation of heterodimers between these proteins and bHLH domain-containing transcription factors abolishes the DNA-binding ability of the latter, thus inhibiting their activity [
]. Id proteins can inhibit the differentiation of progenitors of different cell types, promoting cell-cycle progression, delaying cellular senescence, and facilitating cell migration. These properties enable them to play important roles in stem cell maintenance, vasculogenesis, tumorigenesis and metastasis, the development of the immune system, and energy metabolism [
].
This entry represents a group of ferric binding and related proteins. They are probably part of a periplasmic ABC transporter complex involved in Fe3+ (ferric) ion import, and include FbpA [
], FutA1 [] and FutA2 [].
This family is the Pneumovirus nucleocapsid protein. It is the most abundant protein in the virion and an important element in conferring helical symmetry on the nucleoprotein core as well as interacting with the M protein during virion formation.
Tymoviruses are single stranded RNA viruses. This family includes a protein of unknown function that has been named based on its
molecular weight. Tymoviruses such as the ononis yellow mosaic tymovirus encode only three proteins. Of these two are overlappingthis protein overalps a larger ORF that is thought to be the polymerase [
].
This protein is found in various caulimoviruses. It codes for an 18kDa protein (PII), which is dispensable for infection but which is
required for aphid transmission of the virus []. This protein interacts with the PIII protein [].
This family includes a variety of movement proteins (MP)s. The MP is necessary for the initial cell-to-cell movement during the early stages of a viral infection. This movement is active, and it is known that the MP interacts with the plasmodesmata and possesses the ability to bind to RNA to achieve its role [
]. It has been suggested in cauliflower mosaic virus that these proteins mediated viral movement by modifying plasmodesmata and forming tubules in the channel that can accommodate the virus particles []. The family contains a conserved DXR motif that is probably functionally important.
The movement protein of tobamoviruses is necessary for the initial cell-to-cell
movement during the early stages of a viral infection. This movement is active,and involves the interaction of the movement protein with the plasmodesmata.
The movement protein possesses the ability to bind to RNA to achieve itsrole [
].The N terminus contains two particularly well-conserved regions, substitutions
in one of these results in temperature-sensitive cell-to-cell movement. The C terminus contains three sub-regions characterised by the distributions of chargedamino acid residues [
].
ORF2 of the capilloviruses (trichoviruses) contain a serine peptidase signature which belongs to the MEROPS peptidase family S35 (clan PA(S)). In a number of capilloviruses that have been sequenced to date ORF2 has been identified as the putative movement protein, though it also contains the consensus sequence Gly-Asp-Ser-Gly common to the active site of a number of serine proteases [
]. This family also contains proteins classified as non-peptidase homologues which have either been found experimentally to be without peptidase activity, or lack amino acid residues that are believed to be essential for the catalytic activity of peptidases in the family. Capilloviruses infect a number of different plant species, and can be detected by the presence of virions in leaf sap.
This entry represents large ribosomal subunit protein L21 and mitochondrial ribosomal subunit from yeast L49 (Mrpl49). In S. pombe, the putative mitochondrial ribosomal protein bL21 (Mrpl49) is fused to aconitase [
]. L21 has a small β-barrel-like domain that is connected to an extended loop [].In Escherichia coli, L21 is known to bind to the 23S rRNA in the presence of L20. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities, groups:
Bacterial L21.Marchantia polymorpha chloroplast L21.Cyanelle L21.Plant chloroplast L21 (nuclear-encoded).Bacterial L21 is a protein of about 100 amino-acid residues, the mature form of the spinach chloroplast L21 has 200 residues.
Rodent urinary proteins (mouse major urinary proteins or MUPs and rat alpha-2u globulins) are the
major protein components of rodent urine and transport pheromones [].Rodent urine contains an unusually large amount of protein. The major site of MUP synthesis is the liver; the protein is secreted by the liver into serum,
where it circulates at relatively low levels before being rapidly filteredby the kidney and excreted.
The sex-dependent expression of MUP (adult male mice secrete 5-20 times as much MUP as do females) and its ability to bind a number of odorant
molecules is consistent with the suggestion that MUP acts as a pheromonetransporter; the protein may be excreted into the urine carrying a bound
pheromone, which is released as the urine dries and the protein denatures.The crystal structure of MUP has been solved [
] and is known to be a member of the lipocalin family.
Alpha-2u-globulin, a close homologue of MUP, accounts for 30-50% of totalexcreted protein in adult male rat urine. As its electrophoretic mobility
is similar to that of serum a2 globulin, it was named 'alpha-2u-globulin',the subscript 'u' denoting its origin in urine. Alpha-2u-globulin is
secreted into the plasma by a number of tissues, where it circulates beforefiltration through the kidney; between 20 and 50% is reabsorbed by the
proximal tubule of the nephron, the rest being excreted. Although the exactphysiological role of alpha-2u-globulin is unclear, there is circumstantial
evidence that it functions in pheromone transport. This is consistent withits observed binding properties, its close similarity with MUP and the known
properties of male rat urine.Some of the proteins in this family are allergens. Allergies are hypersensitivity reactions of the immune system to specific substances called allergens (such as pollen, stings, drugs, or food) that, in most people, result in no symptoms. A nomenclature system has been established for antigens (allergens) that cause IgE-mediated atopic allergies in humans [WHO/IUIS Allergen Nomenclature Subcommittee
King T.P., Hoffmann D., Loewenstein H., Marsh D.G., Platts-Mills T.A.E.,Thomas W. Bull. World Health Organ. 72:797-806(1994)]. This nomenclature system is defined by a designation that is composed ofthe first three letters of the genus; a space; the first letter of the
species name; a space and an arabic number. In the event that two speciesnames have identical designations, they are discriminated from one another
by adding one or more letters (as necessary) to each species designation.The allergens in this family include allergens with the following designations: Mus m 1 and Rat m 1.
This entry represents a predicted immunity protein with an alpha+beta fold and a conserved Wea (a: aromatic) motif. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Ntox7 family [
].
This entry represents a predicted immunity protein with an alpha+beta fold and a conserved GxaG motif. They are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a Tox-REase-3 domain [
].
This entry represents a predicted immunity protein with a mostly all-beta fold and GxxE, WxDxRY motifs and a glutamate residue. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, which usually contains toxin domains of the Ntox48 family. This domain is often fused to the Imm71 immunity domain [
].
This entry represents a predicted immunity protein with an alpha+beta fold and a conserved YxC motif. They are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, which usually contains toxin domains of the Tox-JAB1 family []. The immunity protein typically contains a signal peptide and a lipobox.
This entry represents a predicted immunity protein with an alpha+beta fold and a conserved aspartate and GGxP motif. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Ntox10 or Tox-ParB families [
].
This entry represents a predicted immunity protein with an alpha+beta fold and conserved WxG and YxxxC motif. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the NGO1392-family of HNH/Endonuclease VII fold nucleases [
].
This entry represents a predicted immunity protein with a mostly all-beta fold and a conserved arginine residue. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a Pput_2613 deaminase domain [
]. The protein is also found in heterogeneous polyimmunity loci.
Marine teleosts from polar oceans can be protected from freezing in icy
sea-water by serum antifreeze proteins (AFPs) or glycoproteins (AFGPs) [].These function by binding to, and preventing the growth of, ice crystals
within the fish. Despite functional similarity, the proteins arestructurally diverse and include glycosylated and at least 3 non-glycosylated forms: the AFGP of nototheniids and cod are polymers of a
tripeptide repeat, Ala-Ala-Thr, with a disaccharide attached to thethreonine residue; type I AFPs are Ala-rich, α-helical peptides
found in flounder and sculpin; type II AFPs of sea-raven, smelt andherring are Cys-rich proteins; and type III AFPs, found in Eel pouts,
are rich in β-structure. Although no direct structural information is available for type II AFPs,their sequences are similar to the carbohydrate recognition domain (CRD)
of Ca2+-dependent lectins. This domain is present in a superfamily of
proteins that bind sugars specifically through contact with a calciumion. The extent of similarity within the superfamily is confined to
short motifs and single amino acids at intervals throughout the protein.
This entry represents a predicted immunity protein with an alpha+beta fold and a conserved lysine residue. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Tox-URI2 family [
]. The protein is also found in heterogeneous polyimmunity loci.
This family consists of TMEM132A, TMEM132B, TMEM132C, TMEM132D, TMEM132E. They all have transmembrane domains. TMEM132A may play a role in embryonic and postnatal development of the brain. It increased resistance to cell death induced by serum starvation in cultured cells. It regulates cAMP-induced GFAP gene expression via STAT3 phosphorylation [
,
]. TMEM132D is a single-pass transmembrane protein that is highly expressed in the cortical regions of the human and mouse brain. The function is still unknown. It may act as a cell-surface marker for oligodendrocyte differentiation [
,
]. Additionally, as it may be most strongly expressed in neurons and it colocalises with actin filaments, TMEM132D may be implicated in neuronal sprouting and connectivity in brain regions important for anxiety-related behaviour [].
Polymorphic toxins systems consist of secreted toxins, primarily involved in
intra-specific conflict between related strains of prokaryotes. These toxins are as a rule multi-domain and tend to vary their toxin domains through a process of recombination that might replace an existing toxin domain by a distinct one encoded by standalone cassettes, therefore their name as polymorphic toxins. A key feature that distinguishes the polymorphic toxins from conventional toxins (whose primary targets are in distantly related organisms) is the presence of immunity proteins.This entry represents a predicted immunity protein with an alpha+beta fold and YxxxD, WxG, KxxxE motifs. They are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene [
].
