SEBOX is a probable transcription factor involved in preparing oocytes for embryonic development in mice [
]. It is required for early embryonic development in pigs and appears to regulate the degradation of maternal transcripts and the expression of pluripotency genes [].
Apoptosis, or programmed cell death (PCD), is a common and evolutionarily conserved property of all metazoans [
]. In many biological processes, apoptosis is required to eliminate supernumerary or dangerous (such as pre-cancerous) cells and to promote normal development. Dysregulation of apoptosis can, therefore, contribute to the development of many major diseases including cancer, autoimmunity and neurodegenerative disorders. In most cases, proteins of the caspase family execute the genetic programme that leads to cell death.Bcl-2 proteins are central regulators of caspase activation, and play a key role in cell death by regulating the integrity of the mitochondrial and endoplasmic reticulum (ER) membranes [
]. At least 20 Bcl-2 proteins have been reported in mammals, and several others have been identified in viruses. Bcl-2 family proteins fall roughly into three subtypes, which either promote cell survival (anti-apoptotic) or trigger cell death (pro-apoptotic). All members contain at least one of four conserved motifs, termed Bcl-2 Homology (BH) domains. Bcl-2 subfamily proteins, which contain at least BH1 and BH2, promote cell survival by inhibiting the adapters needed for the activation of caspases.Pro-apoptotic members potentially exert their effects by displacing the adapters from the pro-survival proteins; these proteins belong either to the Bax subfamily, which contain BH1-BH3, or to the BH3 subfamily, which mostly only feature BH3 [
]. Thus, the balance between antagonistic family members is believed to play a role in determining cell fate. Members of the wider Bcl-2 family, which also includes Bcl-x, Bcl-w and Mcl-1, are described by their similarity to Bcl-2 protein, a member of the pro-survival Bcl-2 subfamily [
]. Full-length Bcl-2 proteins feature all four BH domains, seven α-helices, and a C-terminal hydrophobic motif that targets the protein to the outer mitochondrial membrane, ER and nuclear envelope. This group represents the Bcl-2-like protein 11 which can induce apoptosis.
SH2 domain-containing protein 1A (SH2D1A) is an adaptor protein that appears to regulate B-cell differentiation via switching of SLAM (CD150)-mediated signalling pathways [
]. The SLAM receptor is expressed on activated T and B lymphocytes. SH2D1A inhibits SLAM self-association. SH2D1A acts by blocking the recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to a docking site in the SLAM cytoplasmic region []. Defects in SH2D1A are a cause of lymphoproliferative syndrome X-linked type 1 (XLP1) (OMIM:308240), which is also known as X-linked lymphoproliferative disease (XLPD) or Duncan disease [
]. XLP is a rare immunodeficiency characterised by extreme susceptibility to infection with Epstein-Barr virus (EBV) (HHV-4) (Human herpesvirus 4). Symptoms include severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma.
This entry represents a group of eukaryotic proteins that are typically between 138 and 164 amino acids in length. They have two completely conserved residues (H and E) that may be functionally important and four transmembrane helices.
This entry represents a group of eukaryotic proteins that are typically between 147 and 280 amino acids in length. There are two conserved sequence motifs: NIRH and SYT. Their function is not known.
This entry represents Tax1-binding protein 3, also known as TIP-1, which is a PDZ domain-containing protein that functions in a wide variety of biological events through selective interaction with different proteins. It interacts with the RhoA effector protein rhotekin [
]. It also associates with glutaminase L [], potassium channel Kir2.3 [] and NMDA receptors []. In humans, Tax1-binding protein 3 has been shown to be involved in the activation of Cdc42 by the viral protein HPV16 E6 []. TIP-1 can have both an oncogenic function or act as a tumor suppressor, probably by modulating the transcriptional activity of beta-catenin [,
].
Spermatogenesis-associated protein 32 (SPATA32, also known as VAD1-2) is expressed in testis and may be involved in acrosome formation during spermiogenesis [
]. VAD1-2 can be detected in the acrosome region of the round and elongated spermatids of mouse, human, monkey and pig. Putative interacting partners syntaxin 1, beta-actin, and myosin heavy chain (MHC) protein were identified from the co-immunoprecipitation experiments [].
This entry represents a predicted immunity protein with mostly all-beta fold and several conserved hydrophobic residues. They are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Tox-URI1 or Tox-HNH family [
]. The protein is also found heterogeneous polyimmunity loci.
TraM is a plasmid encoded DNA-binding protein that is essential for conjugative transfer of F-like plasmids (e.g. F, R1, R100 and pED208) between bacterial cells. Bacterial conjugation, a form of horizontal gene transfer between cells, is an important contributor to bacterial genetic diversity, enabling virulence and antibiotics resistance factors to rapidly spread in medically important human pathogens.Mutation studies have shown that TraM is required for normal levels of transfer gene expression as well as for efficient site-specific single-stranded DNA cleavage at the origin of transfer (oriT). TraM tetramers bridge oriT to a key component of the conjugative pore, the coupling protein TraD. The N-terminal ribbon-helix-helix (RHH) domain of TraM is able to cooperatively bind DNA in a staggered arrangement without interaction between tetramers. This allows the C-terminal TraM tetramerization domains to be free to make multiple interactions with TraD, thus driving plasmid recruitment to the conjugative pore [
,
,
,
].
This family includes Chl4 from budding yeasts, mis15 from fission yeasts and centromere protein N (CENP-N) from animals. In Saccharomyces cerevisiae, Chl4 is an outer kinetochore structural component required for chromosome stability [
]. Chl4 is a component of the Ctf19 kinetochore complex that interacts with Ctf19p, Ctf3p, Iml3p and Mif2p []. It is required for establishing bipolar spindle-microtubule attachments and proper chromosome segregation []. In Schizosaccharomyces pombe, mis15 is a subunit of the Sim4 complex, which is required for loading the DASH complex onto the kinetochore via interaction with dad1 [
]. It is required for correct chromosome segregation where it has a role in the formation and/or maintenance of specialised chromatin at the centromere []. In humans, centromere protein N (CENP-N) is a component of the CENPA-NAC (nucleosome-associated) complex, which plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation [
]. CENP-N localises exclusively in the kinetochore domain of centromeres []. It is required for chromosome congression and efficiently align the chromosomes on a metaphase plate [].
This family consists of remarkably well-conserved proteins from gamma and beta Proteobacteria, heavily skewed towards organisms of marine environments. Its gene neighbourhood is not conserved. This family has an OsmC-like N-terminal domain. It shares a YcaO domain, frequently associated with ATP-dependent cyclodehydration for peptide modification [
]. The function of the family is unknown. A number of members of this family are from selenouridine-positive genomes, but this correlation may not be meaningful.
This entry represents tubulin-like protein CetZ mostly from Archaea. It co-exists with another tubulin-like protein, FtsZ, in many archaea. CetZ is required for differentiation of the irregular plate-shaped cells into a rod-shaped cell type that is essential for normal swimming motility [
].
T-even bacteriophages recognise their cellular receptors with the free ends of their six long tail fibres. The Gp38 protein from bacteriophage T2 and related phages is located at the tip of the tail fibre, where it recognises the host receptor [
]. OmpC has been identified as the host receptor, and sequence variations appear to be an important determinant of host specificity [
].Note this family is not related, either in sequence similairty or function, to the Gp38 protein from bacteriophage T4.
This entry represents Primosomal protein 1 (DnaT) and similar proteins from Proteobacteria. DnaT, a DnaB/C complex loader protein, is required for primosome-dependent normal DNA replication [
]. It is part of the "PriA-PriB"pathway for primosome assembly [
] and is involved in inducing stable DNA replication during SOS response. The N-terminal domain of DnaT is crucial for PriB binding and self-trimerization while the C-terminal domain of DnaT is the DNA-binding domain [].
The CAMSAP family of proteins is defined by a CKK domain that binds microtubules [
]. It includes CAMSAPs from vertebrates and Patronin from invertebrates []. Calmodulin regulated spectrin-associated protein 1 (CAMSAP1) is the representative member. It contains a conserved region, CC1, that binds to both spectrin and Ca2+/calmodulin in vitro and links spectrin-binding to neurite outgrowth []. Patronin binds to and protects the MT minus-end against depolymerization [].
PRIMPOL has both DNA polymerase and DNA/RNA primase activities. It is involved in downstream repriming of stalled forks during both nuclear and mitochondrial DNA replication. It pays an important part in DNA damage tolerance [
]. It is predicted to possess an archaeo-eukaryotic primase and a UL52-like zinc finger domain [,
]. The primase activity of PRIMPOL is essential for many functions in the nucleus. However, the role of PRIMPOL polymerase activity is still unclear, as PRIMPOL synthesizes DNA with limited processivity, rarely incorporating more than four nucleotides on an undamaged template [].
This family of ssRNA negative-strand crop plant tenuivirus proteins appears to combine PV2 [
], NS2 [], NS3, and PV3 proteins.Plant viruses encode specific proteins known as movement proteins (MPs) to control their spread through plasmodesmata (PD) in walls between cells as well as from leaf to leaf via vascular-dependent transport. During this movement process, the virally encoded MPs interact with viral genomes for transport from the viral replication sites to the PDs in the walls of infected cells along the cytoskeleton and/or endoplasmic reticulum (ER) network. The virus is then thought to move through the PDs in the form of MP-associated ribonucleoprotein complexes or as virions [
]. The NS3 protein appears to function as an RNA silencing suppressor [].
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 the VAR1 mitochondrial ribosomal proteins found in yeast and related proteins which are essential for mitochondrial protein synthesis and required for the maturation of small ribosomal subunits [
]. Mitochondria possess their own ribosomes responsible for the synthesis of a small number of proteins encoded by the mitochondrial genome. VAR1 is the only protein in the yeast mitochondrial ribosome to be encoded in the mitochondria - the remaining approximately 80 ribosomal proteins are encoded in the nucleus []. VAR1 along with 15S rRNA are necessary for the formation of mature 37S subunits [].
The small hydrophobic integral membrane protein, SH (previously designated 1A) is found to have a variety of glycosylated forms [
,
]. This protein is a component of the mature respiratory syncytial virion [] where it may form complexes and appears to play a structural role.
Serotype M1 group A Streptococcus strains cause epidemic waves of human infections. This 30 aa repeat occurs in the sic protein, an extracellular protein (streptococcal inhibitor of complement) that inhibits human complement [
].
Cytoplasmic proteins Nck are non-enzymatic adaptor proteins composed of three SH3 (Src homology 3) domains and a C-terminal SH2 domain [
]. They regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates []. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics []. They associate with tyrosine-phosphorylated growth factor receptors or their cellular substrates [,
]. There are two vertebrate Nck proteins, Nck1 and Nck2.
This entry represents a group of proteins from Nematoda, including She-1 from Caenorhabditis briggsae. She-1 is a sex-determining factor which regulates hermaphrodite development [
].
Muscular LMNA-interacting protein (MLIP) is a muscle-enriched A-type Lamin-interacting protein, an innovation of amniotes, and is expressed ubiquitously and most abundantly in heart, skeletal, and smooth muscle. MLIP interacts directly and co-localises with lamin A and C in the nuclear envelope. MLIP also co-localises with promyelocytic leukemia (PML) bodies within the nucleus. PML, like MLIP, is only found in amniotes, suggesting that a functional link between the nuclear envelope and PML bodies may exist through MLIP [
].
This entry represents Gem-associated protein 2 (GEMIN2, also known as SIP1). GEMIN2 is part of the SMN complex, which plays an essential role in spliceosomal snRNP assembly in the cytoplasm and is required for pre-mRNA splicing in the nucleus [
].
Arabinogalactan-proteins (AGPs) are cell wall proteoglycans widely distributed in the plant kingdom. They are thought to have important roles in various aspects of plant growth and development. AGPs are divided into two classes depending upon their core protein: 'classical' and 'nonclassical' AGPs. Classical AGPs contain hydroxyproline (Hyp), Ala, Ser, Thr and Gly as the major amino acid constituents [
]. This entry represents a group of classical arabinogalactan proteins, including AGP1/2/3/4/5/7/10 from Arabidopsis [,
].
This family represents carboxysome assembly proteins, including CsoS2 and S2B (also known as carboxysome shell proteins), which are required for alpha-carboxysome (Cb) assembly and mediate interaction between RuBisCO and the Cb shell [,
,
]. The N-terminal repeats of this intrinsically disordered protein bind simultaneously to both subunits of RuBisCO and minimally 2 N-terminal repeats are necessary for RuBisCO assembly into the Cb in vivo [].
This entry includes SPC24 homologue, MUN (MERISTEM UNSTRUCTURED), from Arabidopsis. SPC24 is part of the outer kinetochore complex NDC80. In Arabidopsis, MUN interacts with components of the NDC80 complex and is required for chromosome segregation to ensure proper cell division [
].
Cenp-K is one of seven new Cenp-A-nucleosome distal (CAD) centromere components (the others being Cenp-L, Cenp-O, Cenp-P, Cenp-Q, Cenp-R and Cenp-S) that are identified as assembling on the Cenp-A nucleosome associated complex, NAC []. The Cenp-A NAC is essential, as disruption of the complex causes errors of chromosome alignment and segregation that preclude cell survival despite continued centromere-derived mitotic checkpoint signalling. Cenp-K is centromere-associated through its interaction with one or more components of the Cenp-A NAC. It may be involved in incorporation of newly synthesized Cenp-A into centromeres via its interaction with the Cenp-A-NAC complex [].The homologue in Schizosaccharomyces pombe is known as inner kinetochore subunit sim4 [
,
].
Chemotaxis inhibitory protein (also knows as CHIPS) is a Staphylococcus aureus-secreted virulence factor that impairs the response of neutrophils and monocytes to FPR and C5a [
]. CHIPS has been shown to reduce neutrophil recruitment toward C5a in mouse models (its activity is more potent on human than on mouse cells). As such, its properties may make it a candidate new anti-inflammatory therapeutic compound [].CHIPS also plays an key role in bacterial invasion, by inhibiting FMLP- and C5a-induced calcium moblisation [
]. By influencing 2 related receptors with very different ligand specificities (C5aR and FPR), the protein has a unique role; nevertheless, neither the manner in which it binds such structurally different molecules nor how its expression is regulated are currently unknown [].The structure of a CHIPS fragment (residues 31-121) has been solved by NMR spectroscopy [
]. This fragment has the same activity in blocking the C5aR relative to full-length CHIPS, but lacks FPR antagonism []. The protein has a compact fold comprising 2 short α-helices packed onto a 4-stranded anti-parallel β-sheet: strands-2 and -3 are joined by a loop with a well-defined conformation []. The protein shares a high degree of structural similarity with a number of proteins, including the C-terminal domain of staphylococcal superantigen-like proteins (SSLs) 5 and 7, staphyloccocal and streptococcal superantigens TSST-1 and SPE-C, and various domains of the staphylococcal extracellullar adherence protein (EAP) [].
Formyl Peptide Receptor-Like 1 (FPRL1)-inhibitory protein (also termed FLIPr) has been shown to inhibit calcium mobilisation in neutrophils [
]. There is evidence that FLIPr binds to FPRL1 and, at higher concentrations, to FPR [], impairing the leukocyte response to FPRL1 agonists. It has revealed unknown inflammatory ligands during S.aureus infection and, as an FPRL1 antagonist, may facilitate development of therapeutic agents in FPRL1-mediated inflammatory diseases [].Chemotaxis inhibitory protein (also knows as CHIPS) is a Staphylococcus aureus-secreted virulence factor that impairs the response of neutrophils and monocytes to FPR and C5a [
]. CHIPS has been shown to reduce neutrophil recruitment toward C5a in mouse models (its activity is more potent on human than on mouse cells). As such, its properties may make it a candidate new anti-inflammatory therapeutic compound [].CHIPS also plays an key role in bacterial invasion, by inhibiting FMLP- and C5a-induced calcium moblisation [
]. By influencing 2 related receptors with very different ligand specificities (C5aR and FPR), the protein has a unique role; nevertheless, neither the manner in which it binds such structurally different molecules nor how its expression is regulated are currently unknown [].The structure of a CHIPS fragment (residues 31-121) has been solved by NMR spectroscopy [
]. This fragment has the same activity in blocking the C5aR relative to full-length CHIPS, but lacks FPR antagonism []. The protein has a compact fold comprising 2 short α-helices packed onto a 4-stranded anti-parallel β-sheet: strands-2 and -3 are joined by a loop with a well-defined conformation []. The protein shares a high degree of structural similarity with a number of proteins, including the C-terminal domain of staphylococcal superantigen-like proteins (SSLs) 5 and 7, staphyloccocal and streptococcal superantigens TSST-1 and SPE-C, and various domains of the staphylococcal extracellullar adherence protein (EAP) [].
The prime candidate for specifying centromere identity is the array of nucleosomes assembles associated with CENP-A [
]. CENP-A recruits a nucleosome associated complex (CENP-A-NAC complex) comprised of CENP-M which this entry represents, along with two other proteins []. Assembly of the CENP-A NAC at centromeres is partly dependent on CENP-M. The CENP-A NAC is essential, as disruption of the complex causes errors of chromosome alignment and segregation that preclude cell survival [].
This family contains proteins of up to five transmembranes helices found in bacterial species, some of which carry a nested PepSY domain. Coil residues are significantly more conserved than other residues and are frequently found within channels and transporters, where they introduce the flexibility and polarity required for transport across the membrane [
].PepSY (peptidase (M4) and YpeB of subtilis) is a repeated region first identified in Thermoanaerobacter tengcongensis. The PepSY domain functions in the control of M4 peptidases through their propeptide and in the germination of spores. It may also play a part in regulating protease activity [
].
In budding yeasts, Spo7 is part of the Nem1-Spo7 protein phosphatase complex which acts as a phosphatase and dephosphorylates the phosphatidic acid phosphohydrolase PAH1 [
]. The Nem1-Spo7 complex mediates regulation of membrane biogenesis is needed to promote mitophagy in yeast [].
Ethanolamine utilization protein EutN/carboxysome shell vertex protein CcmL
Type:
Family
Description:
The ethanolamine utilization protein EutN is involved in the cobalamin-dependent degradation of ethanolamine [
]. The crystal structure of EutN contains a central five-stranded β-barrel, with an α-helix at the open end of this barrel (). The structure also contains three additional β-strands, which help the formation of a tight hexamer, with a hole in the centre. This suggests that EutN forms a pore, with an opening of 26 Amstrong in diameter on one face and 14 Amstrong on the other face []. Beside the Escherichia coli ethanolamine utilization protein EutN and the Synechocystis sp. carboxysome (beta-type) structural protein CcmL, this family also includes alpha-type carboxysome structural proteins CsoS4A and CsoS4B (previously known as OrfA and OrfB), propanediol utilization protein PduN, and some hypothetical homologous of various bacterial microcompartments. The carboxysome, a polyhedral organelle, participates in carbon fixation by sequestering enzymes. It is the prototypical bacterial microcompartment. Its enzymatic components, ribulose bisphosphate carboxylase/oxygenase(RuBisCO) and carbonic anhydrase (CA), are surrounded by a polyhedral protein shell. Similarly, the ethanolamine utilization (eut) microcompartment, and the 1,2-propanediol utilization (pdu) microcompartment encapsulate the enzymes necessary for the process of cobalamin-dependent ethanolamine degradation, and coenzyme B12-dependent degradation of 1,2-propanediol, respectively, within its polyhedral protein shells. It is interesting that both carboxysome structural proteins CcmL and CsoS4A assemble as pentamers in the crystal structures, which might constitute the twelve pentameric vertices of a regular icosahedral carboxysome. However, the reported EutN structure is hexameric rather than pentameric. The absence of pentamers in Eut microcompartments might lead to less-regular icosahedral shell shapes. Due to the lack of structure evidence, the functional roles of the CsoS4A adjacent paralog, CsoS4B, and propanediol utilization protein PduN are not yet clear [
,
,
,
,
,
,
,
,
,
,
,
,
,
,
,
,
,
,
,
,
,
,
,
,
,
,
].This entry represents a family of related bacterial proteins with roles in ethanolamine and carbon dioxide metabolism.
Insect odorant-binding protein A10/Ejaculatory bulb-specific protein 3 superfamily
Type:
Homologous_superfamily
Description:
This entry represents the insect odorant-binding protein A10, also known as OS-D or pherokine-1, and ejaculatory bulb-specific protein 3 (PebIII), also known as pherokine-2 [
]. Odorant binding proteins (OBPs) is a class of small (14-20 Kd) water-soluble proteins first discovered in the insect sensillar lymph but also in the mucus of vertebrates, is postulated to mediate the solubilisation of hydrophobic odorant molecules, and thereby to facilitate their transport to the receptor neurons. The product of a gene expressed in the olfactory system of Drosophila melanogaster (Fruit fly), OS-D, shares features common to vertebrate odorant-binding proteins, but has a primary structure unlike odorant-binding proteins [
]. OS-D derivatives have subsequently been found in chemosensory organs of phylogenetically distinct insects, including cockroaches, phasmids and moths, suggesting that OS-D-like proteins seem to be conserved in the insect phylum.
Inclusion body clearance protein Iml2/Tetratricopeptide repeat protein 39
Type:
Family
Description:
This entry represents a family of proteins conserved from fungi to humans, including fungal Iml2 protein, animal tetratricopeptide repeat protein 39A/B/C (TT39A/B/C) and some characterised proteins. Members of this family carry a tetratricopeptide repeat (
) at their C terminus.
In Saccharomyces cerevisiae, Iml2 and its paralogue-YKR018C are included in this entry. Iml2 localises to the cytoplasm and nucleus [
], and its expression is increased in response to DNA replication stress []. It is found to be involved in lipid droplet-mediated inclusion body clearing after protein folding stress [].In humans TTC39A (also known as DEME6) is expressed in primary breast carcinomas but not in normal breast tissue, and has a putative eukaryotic RNP-1 RNA binding region and a candidate anchoring transmembrane domain. It is coordinately regulated with oestrogen receptor, but is not necessarily oestradiol-responsive [
]. TTC39B has been linked to lipid metabolism [,
].
Myotubularin-related protein 12, protein tyrosine phosphatase-like pseudophosphatase domain
Type:
Domain
Description:
The myotubularin family constitutes a large group of conserved proteins, with 14 members in humans consisting of myotubularin (MTM1) and 13 myotubularin-related proteins (MTMR1-MTMR13). Orthologues have been found throughout the eukaryotic kingdom, but not in bacteria. MTM1 dephosphorylates phosphatidylinositol 3-monophosphate (PI3P) to phosphatidylinositol and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] to phosphatidylinositol 5-monophosphate (PI5P) [,
]. The substrate phosphoinositides (PIs) are known to regulate traffic within the endosomal-lysosomal pathway []. MTMR1, MTMR2, MTMR3, MTMR4, and MTMR6 have also been shown to utilise PI(3)P asa substrate, suggesting that this activity is intrinsic to all active family members. On the other hand, six of the MTM family members encode for catalytically inactive phosphatases. Inactive myotubularin phosphatases contain substitutions in the Cys and Arg residues of the Cys-X5-Arg motif. MTM pseudophosphatases have been found to interact with MTM catalytic phosphatases [
]. The myotubularin family includes several members mutated in neuromuscular diseases or associated with metabolic syndrome, obesity, and cancer [].Myotubularin-related protein 12 (MTMR12), also known 3-phosphatase adapter protein (3-PAP), belongs to the myotubularin family. It is a catalytically inactive phosphatase that plays a role as an adapter for the phosphatase myotubularin to regulate myotubularin intracellular location [
,
]. Knockdown of the mtmr12 gene in zebrafish results in skeletal muscle defects and impaired motor function [].This entry represents the protein tyrosine phosphatase-like pseudophosphatase domain of MTMR12.
Apoptosis-stimulating protein of p53 protein 2, Ras-associating domain
Type:
Domain
Description:
This entry represents the RA domain of ASPP2. ASPP2, also termed Bcl2-binding protein (Bbp), or renal carcinoma antigen NY-REN-51, or tumour suppressor p53-binding protein 2 (53BP2), or p53-binding protein 2 (p53BP2), is a member of ASPP protein family and it functions as a tumour suppressor [,
,
,
]. ASPP2 binds to p53 and enhances p53-mediated transcription of proapoptotic genes. ASSP2 contains a RA domain at the N-terminal. The RA domain is a ubiquitin-like domain and RA domain-containing proteins are involved in several different functions ranging from tumour suppression to being oncoproteins []. All p53 amino acids that are important for ASPP2 binding are mutated in human cancer, and ASPP2 is frequently downregulated in these tumour cells [,
,
,
].
DNA replication protein DnaC/insertion sequence putative ATP-binding protein
Type:
Family
Description:
This group consists of DNA replication protein DnaC and insertion sequence IS21/IS1162 putative ATP-binding proteins. DnaC interacts with DnaB and form a primosome complex for DNA replication [
].
Virulence-associated protein D / CRISPR associated protein Cas2
Type:
Family
Description:
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 [
]. This entry represents members of the family of Cas2, one of the first four protein families found to be associated with prokaryotic genomes containing multiple CRISPR elements. CRISPR systems protect against invasive nucleic acid sequences, including phage. Cas2 proteins have been characterised as either endoribonuclease (for ssRNA) or endodeoxyribonuclease (for dsDNA), depending on the system to which the Cas2 belongs [
]. The cas genes usually are found near the palindromic repeats. It's worth noting that there is a distinct branch of the Cas2 family showing a very low level of sequence identity [
,
].The structural subunit of Cas2, belongs to the VapD family of interferases. The interferase catalytic site is intact in the majority of the Cas2 proteins but is disrupted in some, and is not required for spacer acquisition [
,
].This entry also includes the endoribonuclease VapD [
]. These proteins are defined by a conserved region found at the N terminus of the VapD protein [].
50S ribosomal protein L18Ae/60S ribosomal protein L20 and L18a
Type:
Family
Description:
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 represent the 50S ribosomal protein L18Ae from archaea and 60S ribosomal protein L20/L18a from eukaryotes.
Vacuolar protein sorting-associated protein 13, VPS13 adaptor binding domain
Type:
Domain
Description:
This entry represents the VPS13 adaptor binding (VAB) domain, previously known as SHR-BD, found in VPS13 [
,
]. These proteins interact with membrane-specific adaptor proteins such as Ypt35, Spo71 and the mitochondrial membrane protein Mcp1, to be recruited to different membranes. This domain interacts with Ypt35 which recruits VPS13 to endosomal and vacuolar membranes, and with Mcp1 to target VPS13 at mitochondria []. In plants, this domain is found to be the region which interacts with SHR or the SHORT-ROOT transcription factor, a regulator of root-growth and asymmetric cell division that separates ground tissue into endodermis and cortex. The plant protein containing the SHR-BD is named SHRUBBY or SHBY () [
]. This domain interacts with Proline-X-Proline (Pro-X-Pro) motif present in receptor proteins at contact sites [].This domain comprises six repeated modules, each of them containing nine β-strands connected by loops and arranged into a β-sandwich [
].VPS13 proteins have been implicated in processes including vesicle fusion, autophagy, and actin regulation. They bind phospholipids and act as channels that mediate the transfer of lipids between membranes at organelle contact sites [
,
,
]. It has been proposed that members of this entry have the capacity to bind and likely transfer tens of glycerolipids at once. Yeast VPS13 acts at multiple cellular sites, namely the interface between mitochondria and the vacuole, on endosomes, on the nuclear-vacuole junction and the vacuole, depending on the carbon source and metabolic state. Most evidence showed that mammalian VPS13A, VPS13C and VPS13D localize at contacts between the ER and other organelles, i.e. VPS13A and VPS13D bridge the ER to mitochondria, VPS13C bridges the ER to late endosomes and lysosomes and VPS13B may localize to endosome-endosome contacts [,
,
]. Mutations in human VPS13 proteins (VPS13A-D) cause different diseases such as Chorea-acanthocytosis, Cohen syndrome, Parkinson's disease, and spastic ataxia, respectively which suggests they have different functions [,
]. Members of this entry belong to the repeating β-groove (RBG) superfamily. These proteins share a structure made of multiple repeating modules consisting of five β-sheets followed by a loop [].
Proline/serine-rich coiled-coil protein 1/G2 and S phase-expressed protein 1
Type:
Family
Description:
This is a family of phosphoproteins which includes proline/serine-rich coiled-coil protein 1 (PSRC1, also known as DDA3) and G2 and S phase-expressed protein 1 (GTSE1).DDA3 is a microtubule-destabilising protein that controls spindle dynamics and mitotic progression by regulating microtubule depolymerases, such as Kif2a and MCAK [
,
]. Deletion of DDA3 causes spindle hyper-stabilisation, inter-kinectochore tension loss, chromosome congression defects. This leads to unaligned chromosomes at metaphase and the accumulation of CENP-E (a plus end-motor protein) at kinectochore in these chromosomes []. It has also been suggested that DDA3 may participate in p53/TP53-regulated growth suppression []. GTSE1 may be involved in p53-induced cell cycle arrest in G2/M phase by interfering with microtubule rearrangements that are required to enter mitosis [
]. When overexpressed, GTSE1 delays G2/M phase progression [].
Protein of unknown function DUF1924, Cytochrome c-type protein SHP-like
Type:
Family
Description:
This family of proteins includes Cytochrome c-type proteins from proteobacteria, such as Cytochrome c-type protein SHP from Rhodobacter sphaeroides (
), a high-spin cytochrome able to transiently bind oxygen during autoxidation. It is organized into a series of four α-helices and extended loop configuration, showing structural similarity to the class I cytochromes c. It has been suggested that SHP could reduce a small ligand, but its function is still unknown [
].
40S ribosomal protein S29/30S ribosomal protein S14 type Z
Type:
Family
Description:
This entry includes eukaryote 40S ribosomal protein S29 and archaeal 30S ribosomal protein S14 type Z. They belong to the zinc-binding subfamily of ribosomal protein S14. They bind 1 zinc ion per subunit and bind to the 16S rRNA [
]. S14 is required for the assembly of 30S particles and may also be responsible for determining the conformation of the 16S rRNA at the A site.
Ribosomal RNA-processing protein 14/surfeit locus protein 6, C-terminal domain
Type:
Domain
Description:
This entry represents the C-terminal domain of the ribosomal RNA-processing protein 14 (Rrp14), which shares protein sequence similarity with surfeit locus protein 6 (SURF6). In mammals, SURF6 is a component of the nucleolar matrix and has a strong binding capacity for nucleic acids [
]. SURF6 is always found in the nucleolus regardless of the phase of the cell cycle suggesting that it is a structural protein constitutively present in nucleolar substructures. A role in rRNA processing has been proposed for this protein. Saccharomyces cerevisiae member of the SURF-6 family, named Rrp14 (ribosomal RNA-processing protein 14), interacts with proteins involved in ribosomal biogenesis and cell polarity [
]. It is required for the synthesis of both 40S and 60S ribosomal subunits and may also play some direct role in correct positioning of the mitotic spindle during mitosis [,
].
Periodic tryptophan protein 2 (also known as UTP1) is involved in nucleolar processing of pre-18S ribosomal RNA [
]. In budding yeast, it is a component of the ribosomal small subunit (SSU) processome composed of at least 40 protein subunits and snoRNA U3 [].
Elongator complex protein 1 (also known as Iki3) is a component of the RNA polymerase II elongator complex, which is a major histone acetyltransferase component of the RNA polymerase II (RNAPII) holoenzyme. The eukaryotic elongator complex has been associated with many cellular activities, including transcriptional elongation [
,
], but its main function is tRNA modification [,
]. It is required for the formation of 5-methoxy-carbonylmethyl (mcm5) and 5-carbamoylmethyl (ncm5) groups on uridine nucleosides present at the wobble position of many tRNAs [].
Nup84 forms a complex with five proteins, including Nup120, Nup85, Sec13, and a Sec13 homologue. This Nup84 complex in conjunction with Sec13-type proteins is required for correct nuclear pore biogenesis [
]. Nup107 is the vertebrate homologue of Nup84. The Nup107-160 complex (Nup84 complex in yeast) forms the cytoplasmic and nucleoplasmic rings of the nuclear pore complex (NPC) scaffold, which consists of three stacked rings [].
Mini-chromosome maintenance complex-binding protein
Type:
Family
Description:
This entry represents a family of proteins which are approximately 600 residues in length and contain alternating regions of conservation and low complexity. They are associated components of the mini-chromosome maintenance (MCM) complex that acts as a regulator of DNA replication. They bind to the MCM complex during late S phase and promotes the disassembly of the MCM complex from chromatin, thereby acting as a key regulator of pre-replication complex (pre-RC) unloading from replicated DNA. Can dissociate the MCM complex without addition of ATP; probably acts by destabilising interactions of each individual subunits of the MCM complex. Required for sister chromatid cohesion [
,
].
Chlororespiratory reduction 6 is a factor required for the assembly or stabilisation of the chloroplast NAD(P)H dehydrogenase complex in Arabidopsis [
].
This domain is found in N-terminal of the telomere-associated protein,Rif1. In budding yeast, Rif1 is Recruited to telomeres by interaction with the C terminus of RAP1 is recruited to telomeres by interaction with the C terminus of RAP1 and negatively regulates telomere length by preventing telomere elongation or promoting degradation of the telomere ends [
,
]. In mammals, Rif1 is required for checkpoint mediated arrest of cell cycle progression in response to DNA damage during S-phase (the intra-S-phase checkpoint) [].
Ribosomal protein L11 methyltransferase (PrmA) (
) is required for the methylation of ribosomal protein L11. It forms a bifunctional operon in Escherichia coli with panF (pantothenate transport). In E. coli, it trimethylates the N-terminal alpha-amino group and the ε-amino groups of Lys3 and Lys39 [
]. In Arabidopsis is targeted to both mitochondria and chloroplasts. Structures comparison with the E. coli enzyme revealed that they share similar product specificity but display a difference in substrate site specificity [].
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 L3 is one of the proteins from the large ribosomal subunit. In Escherichia coli, L3 is known to bind to the 23S rRNA and may participate in the formation of the peptidyltransferase centre of the ribosome. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities includes bacterial, red algal, cyanelle, mammalian, yeast and Arabidopsis thaliana L3 proteins; archaeal Haloarcula marismortui
HmaL3 (HL1), and yeast mitochondrial YmL9 [,
,
].This entry represents archaeal L3 proteins.
The F-actin capping protein binds in a calcium-independent manner to the fast growing ends of actin filaments (barbed end) and thereby restricts its growth. The F-actin capping protein is a heterodimer composed of two unrelated subunits: alpha and beta. Neither of the subunits shows sequence similarity to other filament-capping proteins [
].This entry represents the beta subunit (CAPZB), which is a protein of about 280 amino acid residues whose sequence is well conserved in eukaryotic species [
]. In Drosophila mutations in the alpha and beta subunits cause actin accumulation and subsequent retinal degeneration []. In humans CAPZB is part of the WASH complex that controls the fission of endosomes [].
This is a family of proteins that contain a highly conserved DDRGK motif. In humans, DDRGK domain-containing protein 1 is a substrate adapter for ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to substrate proteins, which plays a key role in reticulophagy (also called ER-phagy) [
]. It is also involved in cartilage development through SOX9, inhibiting the ubiquitin-mediated proteasomal degradation of this transcriptional regulator [].
Protein tyrosine (pTyr) phosphorylation is a common post-translational modification which can create novel recognition motifs for protein interactions and cellular localisation, affect protein stability, and regulate enzyme activity. Consequently, maintaining an appropriate level of protein tyrosine phosphorylation is essential for many cellular functions. Tyrosine-specific protein phosphatases (PTPase;
) catalyse the removal of a phosphate group attached to a tyrosine residue, using a cysteinyl-phosphate enzyme intermediate. These enzymes are key regulatory components in signal transduction pathways (such as the MAP kinase pathway) and cell cycle control, and are important in the control of cell growth, proliferation, differentiation and transformation [
,
]. The PTP superfamily can be divided into four subfamilies []:(1) pTyr-specific phosphatases(2) dual specificity phosphatases (dTyr and dSer/dThr)(3) Cdc25 phosphatases (dTyr and/or dThr)(4) LMW (low molecular weight) phosphatasesBased on their cellular localisation, PTPases are also classified as:Receptor-like, which are transmembrane receptors that contain PTPase domains [
]
Non-receptor (intracellular) PTPases [
]
All PTPases carry the highly conserved active site motif C(X)5R (PTP signature motif), employ a common catalytic mechanism, and share a similar core structure made of a central parallel β-sheet with flanking α-helices containing a β-loop-α-loop that encompasses the PTP signature motif [
]. Functional diversity between PTPases is endowed by regulatory domains and subunits. This entry represents the low molecular weight (LMW) protein-tyrosine phosphatases (or acid phosphatase), which act on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates [
,
]. The structure of a LMW PTPase has been solved by X-ray crystallography [] and is found to form a single structural domain. It belongs to the alpha/beta class, with 6 α-helices and 4 β-strands forming a 3-layer α-β-alpha sandwich architecture.
This entry represents proteins annotated as Ycf55. It is found encoded in the chloroplast genomes of algae, it is also found in plants and in the cyanobacteria. The function is unknown, though there are two completely conserved residues (L and D) that may be functionally important. As the family is exclusively found in phototrophic organisms it may play a role in photosynthesis. Some members of this family are predicted to be response regulators because they contain an N-terminal CheY-like receiver domain.
This family consists of chloroplast encoded Ycf2, which is around 2000 residues in length. The function of Ycf2 is unknown, though it may be an ATPase. Its retention in reduced chloroplast genomes of non-photosynthetic plants, e.g. Epifagus virginiana (Beechdrops), and transformation experiments in tobacco indicate that it has an essential function which is probably not related to photosynthesis [
].
Ribosomal protein S2, bacteria/mitochondria/plastid
Type:
Family
Description:
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 describes the bacterial, archaea, mitochondrial and chloroplast forms of ribosomal protein S2.
This family includes includes Protein CHLORORESPIRATORY REDUCTION 42 (CRR42) from Arabidopsis thaliana, which is required for both formation and activity of the chloroplast NAD(P)H dehydrogenase (NDH) complex of the photosynthetic electron transport chain [
]. CRR42 functions in assembly or stabilization of the NDH complex and it is likely involved, together with CRR1 and CRR6, in the incorporation of NdhJ, NdhM, NdhK and NdhI into the NDH subcomplex A assembly intermediate (NAI500) to produce the complex NAI400 []. This family also includes uncharacterised proteins from cyanobacteria.
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 chloroplast ribosomal protein S5 as well as bacterial ribosomal protein S5. A candidate mitochondrial form (Saccharomyces cerevisiae YBR251W and its homologues) differs substantially and is not included in this model.
DevT (Alr4674) is a putative protein phosphatase from Nostoc PCC 7120 (Anabaena PCC 7120) [
]. DevT mutants form mature heterocysts, but they are unable to fix N(2) and must be supplied with a source of combined nitrogen in order to survive. Anabaena DevT shows homology to phosphatases of the PPP family and displays a Mn(2+)-dependent phosphatase activity. DevT is constitutively expressed in both vegetative cells and heterocysts, and is not regulated by NtcA. The heterocyst regulator HetR may exert a certain inhibition on the expression of devT. Under diazotrophic growth conditions, DevT protein accumulates specifically in mature heterocysts. The role that DevT plays in a late essential step of heterocyst differentiation is still unknown.
Members of this family are integral membrane proteins involved in protein trafficking between the late Golgi and endosome. They may also serve as a receptor for ADP-ribosylation factor-related protein 1 (ARFRP1) [
]. Sys1p is a small integral membrane protein with four predicted transmembrane domains that localises to the Trans Golgi network TGN in yeast and human cells [].
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 specifically bacterial, chloroplast, and mitochondrial ribosomal protein S15. The homologous proteins of Archaea and Eukarya are designated S13. Escherichia coli ribosomal protein S15 has been shown to regulate the expression of its own mRNA by a feedback mechanism at the translational level. The translational
operator overlaps the ribosome binding site and folds into two mutually exclusive structures, one consisting of two stem-loops (I and II) and the other oneforming a pseudoknot. The two structures, which seem to be energetically equivalent are in dynamic equilibrium, and the
pseudoknot is stabilised by binding of S15. However, binding of S15 does not prevent 30 S subunit binding but traps the subunit into an incompetenttranslation initiation complex. Repression can be alleviated by 16 S rRNA, which is able to displace the bound S15, thus allowing translation to
proceed [].
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 S3 is one of the proteins from the small ribosomal subunit.
This family describes the bacterial type of ribosomal protein S3 and also and many chloroplast forms. Chloroplast and mitochondrial forms have large, variable inserts between conserved N-terminal and C-terminal domains.
Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product.PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane [
,
,
]. Within the core of the complex, the chlorophyll and beta-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection []. This family represents the D2 protein (PsbD), which forms the reaction core of PSII as a heterodimer with the D1 protein. The accumulation of D2 protein appears to be a key step in the assembly of the PSII reaction centre complex [
]. In higher plants, the N-terminal residues of both proteins, which are exposed to the stromal surface, can be reversibly phosphorylated. The D1/D2 core binds to a number of cofactors, including: a 4-atom manganese cluster, which is located on the lumenal surface of the D1 and D2 proteins []; two pheophytin molecules, only one of which is phytochemically active; non-haem iron; and two quinones, Qa (bound to D2) and Qb (bound to D1). Upon light excitation, an electron is transferred from the primary donor (chlorophyll a) via intermediate acceptor pheophytin to the primary quinone Qa, then to the secondary quinone Qb. At the oxidising side of PSII, a redox-active residue in the D1 protein reduces P680, the oxidised tyrosine then withdrawing electrons from a manganese cluster, which in turn withdraw electrons from water, leading to the splitting of water and the formation of molecular oxygen. PSII thus provides a source of electrons that can be used by photosystem I to produce the reducing power (NADPH) required to convert CO2 to glucose.
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 S4, is one of the primary rRNA binding proteins, it binds directly to 16S rRNA where it nucleates assembly of the body of the 30S subunit. This entry consists of organelle (chloroplast and mitochondrial) ribosomal protein S4 as well as bacterial ribosomal protein S4.
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.
Members of this family are PsaC, an essential component of photosystem I (PS-I) reaction centre in Cyanobacteria and chloroplasts. This small protein, about 80 amino acids in length, contains two copies of the ferredoxin-like 4Fe-4S binding site and therefore eight conserved Cys residues. This protein is also called photosystem I subunit VII.
RadA/Sms is a highly conserved eubacterial protein that shares sequence similarity with both RecA strand transferase and lon protease. The RadA/Sms family are ATP-dependent proteases involved in both DNA repair and degradation of proteins, peptides, glycopeptides. They are classified in MEROPS peptidase family S16 (lon protease family, clan SJ).RadA/Sms is involved in recombination and recombinational repair, most likely involving the stabilisation or processing of branched DNA molecules or blocked replication forks [
,
].
This family of plant transcription factors includes GLABROUS1 enhancer-binding protein (GeBP) and GeBP-like proteins, and storekeeper and storekeeper-like (STKL) transcription factors.GeBP and GeBP-like proteins play a redundant role in cytokinin hormone pathway regulation [
]. Storekeeper was identified as a B-box motif binding factor that regulates expression of patatin, a storage protein in potato []. Storekeeper-like transcription factors STKL1 and STKL2 function as transcription factors in the glucose signaling pathway [].
The GDP dissociation inhibitor for rho proteins, rho GDI, regulates GDP/GTP exchange by inhibiting the dissociation of GDP from them. The protein contains 204 amino acids, with a calculated Mr value of 23,421. Hydropathy analysis shows it to be largely hydrophilic, with a single hydrophobic region. The protein plays an important role in the activation of the superoxide (O2-)-generating NADPH oxidase of phagocytes. This process requires the interaction of membrane-associated cytochrome b559 with 3 cytosolic components: p47-phox, p67-phox and a heterodimer of the small G-protein p21rac1 and rho GDI [
]. The association of p21rac and GDI inhibits dissociation of GDP from p21rac, thereby maintaining it in an inactive form. The proteins are attached via a lipid tail on p21rac that binds to the hydrophobic region of GDI []. Dissociation of these proteins might be mediated by the release of lipids (e.g., arachidonate and phosphatidate) from membranes through the action of phospholipases []. The lipids may then compete with the lipid tail on p21rac for the hydrophobic pocket on GDI.Two homologues of rho GDP-dissociation inhibitors have been identified in Dicytostelium: GDI1 and GDI2. They are cytosolic proteins. GDI1 has been found to play a central role in cytokinesis through the regulation of Rho family GTPases Rac1s and/or RacE [
,
].Rho GDI in yeast has been shown to have similar properties as mammalian rho GDI [
].
This entry represents the N-terminal domain of GBF1-interacting protein 1 (GIP1, AT3G13222) from Arabidopsis. GIP1 may act as a coactivator that regulates transcription factors involved in lateral organ development of plants, such as bZIP transcription factors and LBD18 [
,
].
Members of this family are involved in the negative regulation of gluconeogenesis. They are required for both proteosome-dependent and vacuolar catabolite degradation of fructose-1,6-bisphosphatase (FBPase), where they probably regulate FBPase targeting from the FBPase-containing vesicles to the vacuole [
,
].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].This entry includes yeast MRPL37 a mitochondrial ribosomal protein [
].
Human coiled-coil domain-containing protein 22 (CCDC22) is involved in regulation of NF-kappa-B signalling; the function may involve association with COMMD8 and a CUL1-dependent E3 ubiquitin ligase complex [
]. It is part of the OMMD/CCDC22/CCDC93 (CCC) complex, which interacts with the multisubunit WASH complex required for endosomal deposition of F-actin and cargo trafficking in conjunction with the retromer [].This entry also includes CCDC22 homologues from animals and plants.
Ribosomal protein S13 is one of the proteins from the small ribosomal subunit [
]. In Escherichia coli, S13 is known to be involved in binding fMet-tRNA and, hence, in the initiation of translation. S13 contains thee helices and a β-hairpin in the core of the protein, which form a helix-two turns-helix (H2TH) motif, and a non-globular C-terminal extension.This H2TH motif can be found in other proteins as well. In the DNA repair protein, MutM (formamidopyrimidine DNA glycosylase; Fpg), the middle domain contains the H2TH motif. MutM is a trifunctional DNA base excision repair enzyme that removes a wide range of oxidatively damaged bases (N-glycosylase activity) and cleaves both the 3'- and 5'-phosphodiester bonds of the resulting apurinic/apyrimidinic site (AP lyase activity) [
]. Other repair enzymes, such as E. coli Endonuclease VIII that excises oxidized pyrimidines from DNA, also contain a DNA-binding H2TH motif within the middle domain. The H2TH domains of these repair proteins are only peripherally involved in binding DNA; their primary function may be simply to position the N-terminal lobe and C-terminal zinc finger domain of the glycosylases for interactions with DNA.The middle domain of topoisomerase IV-B subunit contains a H2TH motif that is structurally related to the DNA repair proteins. Although the H2TH domain appears to be retained in all archaeal and plant type IIB topoisomerases identified to date, it has no known function and has not been observed in other topoisomerase families [].
Proteins containing a RhoGAP (Rho GTPase Activating Protein) domain usually function to catalyse the hydrolysis of GTP that is bound to Rho, Rac and/or Cdc42, inactivating these regulators of the actin cytoskeleton. The 53 known human RhoGAP domain-containing proteins are the largest known group of Rho GTPase regulators and significantly outnumber the 21 Rho GTPases they presumably regulate. This excess of GAP proteins probably indicates complex regulation of the Rho GTPases and is consistent with the existence of almost as many (48) human Dbl domain-containing Rho GEFs that act antagonistically to the RhoGAP proteins by activating the Rho GTPases. Phylogenetic analysis offers evidence for frequent domain duplication and for duplication of the entire genes containing these GAP domains [
].
Members of the Rho family of small G proteins transduce signals from plasma-membrane
receptors and control cell adhesion, motility and shape by actin cytoskeleton formation.Like all other GTPases, Rho proteins act as molecular switches, with an active
GTP-bound form and an inactive GDP-bound form. The active conformation is promoted byguanine-nucleotide exchange factors, and the inactive state by GTPase-activating proteins
(GAPs) which stimulate the intrinsic GTPase activity of small G proteins.This entry is a Rho/Rac/Cdc42-like GAP domain, that is found in a wide variety of large,
multi-functional proteins [].A number of structure are known for this family
[,
,
].The domain is composed of seven α-helices.
This domain is also known as the breakpoint cluster region-homology (BH) domain.
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 have been grouped on the basis of sequence similarities. Ribosomal protein S6 is the major substrate of protein kinases in eukaryotic ribosomes [
] and may play an important role in controlling cell growth and proliferation through the selective translation of particular classes of mRNA.
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 [
,
].L6 is a protein from the large (50S) subunit. In Escherichia coli, it is located in the aminoacyl-tRNA binding
site of the peptidyltransferase centre, and is known to bind directly to 23S rRNA. It belongs to a family of ribosomal proteins, including L6 from bacteria, cyanelles (structures that perform similar functions to chloroplasts, but have structural and biochemical characteristics of Cyanobacteria) and mitochondria; and L9 from mammals, Drosophila, plants and yeast. L6 contains two domains with almost identical folds, suggesting that is was derived by the duplication of an
ancient RNA-binding protein gene. Analysis reveals several sites on the protein surface where interactions with other ribosome components may occur, the N terminus being involved in protein-protein interactions and the C terminus containing possible RNA-binding sites [].
This entry includes SKP1 and SKP1-like protein, elongin-C (also known as TCEB1). SKP1 is part of the E3 ubiquitin ligase complexes. Elongin-C has dual functions, works as a component of RNA polymerase II (Pol II) transcription elongation factor and as the substrate recognition subunit of a Cullin-RING E3 ubiquitin ligase []. Mammlian S-phase kinase-associated protein 1 (SKP1) is an essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription [
]. It is also part of the ubiquitin E3 ligase complex (Skp1-Pam-Fbxo45) that controls the core epithelial-to-mesenchymal transition-inducing transcription factors []. Budding yeast Skp1 is a kinetochore protein found in several complexes, including the SCF ubiquitin ligase complex, the CBF3 complex that binds centromeric DNA [], and the RAVE complex that regulates assembly of the V-ATPase []. Elongin-C is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites [
]. It forms a complex with SIII regulatory subunits B, which serves as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes []. Elongin-C forms a complex with Cul3 that polyubiquitylates monoubiquitylated RNA polymerase II to trigger its proteolysis [].
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 the C-terminal domain of the large subunit ribosomal proteins, known as the L7/L12 family. L7/L12 is present in each 50S subunit in four copies organised as two dimers. The L8 protein complex consisting of two dimers of L7/L12 and L10 in Escherichia coli ribosomes is assembled on the conserved region of 23 S rRNA termed the GTPase-associated domain [
]. The L7/L12 dimer probably interacts with EF-Tu. L7 and L12 only differ in a single post translational modification of the addition of an acetyl group to the N terminus of L7.
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 L7/12 consists of two domains that are connected by a flexible region. The N-terminal domain is required for dimer formation and for anchoring the protein to the ribosome by binding to ribosomal protein L10, while the C-terminal domain is required for translation factors binding [
].
There are two types of fatty acid synthase systems. The type I system is found in metazoans and is carried out
by a multifunctional polypeptide with multiple active sites. In contrast, the type II system found in bacteria and plantsconsists of a set of discrete monofunctional proteins, each encoded by a separate gene. ACP1 is central to both of these
pathways because it functions to ferry the pathway intermediates between active site centres or enzymes. ACPs are alsocritical to the function of other metabolic pathways such as polyketide synthases. The type II fatty acid synthase ACPs are abundant, small, acidic proteins that carry the acyl intermediates attached as thioesters to the terminus of the 4'-phosphopantetheine prosthetic group. This prosthetic group is added post-translationally to apoACP by holo-(acyl carrier protein) synthase (AcpS), which transfers the 4'-phosphopantetheine moiety of CoA to a serine reidue of apoACP.The crystal structures of a number of the type II fatty acid synthase ACPs have been determined. The structures reveal a novel trimeric arrangement of molecules resulting in three active sites [
,
].
This family describes eukaryotic S5 ribosomal proteins and archaeal S7 ribosomal proteins.Ribosomal protein (RP)S5 has variable N-terminal regions that affect the efficiency of initiation translation process by impacting small ribosomal subunit to function [
]. RPS7 is located at the head of the small subunit which is a primary ribosomal RNA (rRNA) binding protein that assists in rRNA folding and the binding of other proteins during small subunit assembly in all species. RPS7 is also involved in the formation of the mRNA exit channel at the interface of the large and small subunits [,
,
].
Obg subfamily proteins (also known as ObgE, YhbZ and CgtA) are conserved P- loop GTPases, that are involved in a wide range of cellular processes, including sporulation, cellular differentiation, ribosome assembly, DNA replication, chromosome segregation, and stringent response in eubacteria and plant chloroplasts. Obg subfamily proteins have three domains: the Obg fold, the G domain, and the Obg C-terminal (OCT) domain. A potential role of the OCT domain in the regulation of the nucleotide-binding state has been suggested [
,
,
]. The OCT domain structure contains a four-stranded beta sheet and three alpha helices flanked by an additional beta strand []. This entry represents the OCT domain.
Protein farnesyltransferase (FTase) is an enzyme responsible for the posttranslational modification (farnesylation) of proteins carrying a carboxy-terminal CaaX motif, including Ras, Ras homologues, and other small G proteins. FTase catalyses the transfer of a farnesyl moiety from farnesyl pyrophosphate to the cysteine at the CaaX motif, where a is a small aliphatic amino acid and X is the carboxy-terminal residue [
,
]. Prenyltransferase employ a Zn2+ ion to alkylate a thiol group catalyzing the formation of thioether linkages between cysteine residues at or near the C terminus of protein acceptors and the C1 atom of isoprenoid lipids. FTase attaches a 15-carbon farnesyl group to the cysteine within the C-terminal CaaX motif of substrate proteins when X is Ala, Met, Ser, Cys or Gln [,
,
]. FTase is a heterodimeric complex comprised of a regulatory alpha subunit shared with geranylgeranyltransferase I (also a CaaX prenyltransferase) and a unique catalytic beta subunit [
]. FTase plays important roles in the growth and differentiation of eukaryotic cells. It is essential for embryonic proliferation, but dispensable for adult homeostasis []. In plants, is involved in abscisic acid signal transduction, which modulates a variety of developmental processes and responses to environmental stress []. In yeast, protein farnesylation is important for maintaining normal cell morphology [] and for cell cycle progression [].
This entry includes Arabidopsis MIZU-KUSSEI 1 (MIZ1), which is an essential protein for hydrotropism in roots. It can be regulated by light signal and ABA signalling [,
].
Polyadenylate-binding protein/Hyperplastic disc protein
Type:
Domain
Description:
The polyadenylate-binding protein (PABP) has a conserved C-terminal domain (PABC), which is also found in the hyperplastic discs protein (HYD) family of ubiquitin ligases that contain HECT domains (
) [
]. PABP recognises the 3' mRNA poly(A) tail and plays an essential role in eukaryotic translation initiation and mRNA stabilisation/degradation. PABC domains of PABP are peptide-binding domains that mediate PABP homo-oligomerisation and protein-protein interactions. In mammals, the PABC domain of PABP functions to recruit several different translation factors to the mRNA poly(A) tail [].
This family includes ribosomal L4/L1 from most organellar forms, but excludes homologues from the eukaryotic cytoplasm and from archaea. The L4 protein from yeast has been shown to bind rRNA [
]. 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 [,
].Ribosomal protein L30 is one of the proteins from the large ribosomal subunit. L30 belongs to a family of ribosomal proteins which, on the basis of sequence similarities, groups bacteria and archaea L30, yeast mitochondrial L33, and Drosophila, slime mould, fungal and mammalian L7 ribosomal proteins. L30 from bacteria are small proteins of about 60 residues. This model describes bacterial, chlorplast and mitochondrial forms of ribosomal protein L30, as well as some yeast mitochondrial L33.
Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, is an essential cofactor for nearly 60 Escherichia coli enzymes and 140 human enzymes. It is a highly reactive molecule that is toxic in its free form. The E. coli PROSC, known as yggS, binds to PLP and is involved in PLP homeostasis, supplying this cofactor to apoenzymes while minimizing any toxic side reactions [
,
]. Proteins in this entry occur in archaea, bacteria and eukaryotes. The bacterial proteins are co-transcribed with proline biosysnthesis genes, hence this group of proteins are also named the proline synthetase co-transcribed homologues (PROSC) [
].The structure of the yeast protein (
) has been determined to a resolution of 2.0 A [
]. Similar in structure to the N-terminal domains of alanine racemase and ornithine decarboxylase, it forms a TIM barrel fold which begins with a long N-terminal helix, rather than the classical beta strand found at the beginning of most other TIM barrels. Unlike alanine racemase and ornithine decarboxylase, which are two-domain dimeric proteins, the yeast protein is a single domain monomer. A pyridoxal 5'-phosphate cofactor is covalently bound towards the C-terminal end of the barrel, which is the usual active site in TIM-barrel folds. Some racemase activity was observed for this protein and it was suggested by the authors that it may function as a general racemase [].
The mammalian B-cell receptor-associated proteins of 29 and 31kDa (BAP29 and BAP31) are integral membrane proteins with a role in endoplasmic reticulum (ER) quality control and sorting [
,
,
]. BAP31 is also involved in apoptosis []. Saccharomyces cerevisiae possesses three homologues of BAP31 known as Yet1, Yet2, and Yet3 [].
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 model decribes bacterial and chloroplast ribosomal protein L22
This family consists of BRX1 and homologues. In yeast, BRX1 is part of a complex that also includes RPF1, RPF2 and SSF1 or SSF2. It is required for biogenesis of the 60S ribosomal subunit [
].
UreD is a urease accessory protein. Urease hydrolyses urea into ammonia and carbamic acid [
]. UreD is involved in activation of the urease enzyme via the UreD-UreF-UreG-urease complex [] and is required for urease nickel metallocentre assembly []. This entry includes UreH from Helicobacter pylori, which is an orthologue of UreD [].
