Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase implicated
in many cellular processes, including the regulation of metabolic enzymes and proteins involved in signal transduction [
,
]. PP2A is a trimercomposed of a 36kDa catalytic subunit, a 65kDa regulatory subunit
(subunit A) and a variable third subunit (subunit B) [,
]. Subunits B can be classified into three subfamilies, the R2/B/PR55/B55, the R3/B''/PR72/PR130/PR59 and the R5/B'/B56 families. This entry represent the R2/B/PR55/B55 family, which exists in
Drosophila melanogaster and yeast, and has up to three isoforms in mammals (alpha/beta/gamma) [,
]. PR55 may act as a substrate recognition unit, or may help to target the enzyme to thecorrect subcellular location [
]. In budding yeasts, it is also known as Cdc55, which is essential for the spindle assembly checkpoint (SAC) []. In flies, it is also known as PP2A-twins, which collaborates with polo kinase for cell cycle progression and centrosome attachment to nuclei in Drosophila embryos [].
Protein phosphatase 2A regulatory subunit PR55, conserved site
Type:
Conserved_site
Description:
Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase implicated
in many cellular processes, including the regulation of metabolic enzymes and proteins involved in signal transduction [
,
]. PP2A is a trimercomposed of a 36kDa catalytic subunit, a 65kDa regulatory subunit
(subunit A) and a variable third subunit (subunit B) [,
].One form of the third subunit is a 55kDa protein (PR55), which exists in
Drosophila melanogaster and yeast, and has up to three forms in mammals [,
]. PR55 may actas a substrate recognition unit, or may help to target the enzyme to the
correct subcellular location [].This entry represents conserved regions found in the N-terminal region and the centre of these proteins.
ATP synthase, F0 complex, subunit G, mitochondrial
Type:
Family
Description:
This entry represents the G subunit found in the F0 complex of F-ATPases in mitochondria. The function of subunit G is currently unknown. There is no counterpart in chloroplast or bacterial F-ATPases identified so far [
].Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP. There are several different types of transmembrane ATPases, which can differ in function (ATP hydrolysis and/or synthesis), structure (e.g., F-, V- and A-ATPases, which contain rotary motors) and in the type of ions they transport [,
]. The different types include:F-ATPases (ATP synthases, F1F0-ATPases), which are found in mitochondria, chloroplasts and bacterial plasma membranes where they are the prime producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts).V-ATPases (V1V0-ATPases), which are primarily found in eukaryotes and they function as proton pumps that acidify intracellular compartments and, in some cases, transport protons across the plasma membrane [
]. They are also found in bacteria [].A-ATPases (A1A0-ATPases), which are found in Archaea and function like F-ATPases, though with respect to their structure and some inhibitor responses, A-ATPases are more closely related to the V-ATPases [
,
].P-ATPases (E1E2-ATPases), which are found in bacteria and in eukaryotic plasma membranes and organelles, and function to transport a variety of different ions across membranes.E-ATPases, which are cell-surface enzymes that hydrolyse a range of NTPs, including extracellular ATP.F-ATPases (also known as ATP synthases, F1F0-ATPase, or H(+)-transporting two-sector ATPase) (
) are composed of two linked complexes: the F1 ATPase complex is the catalytic core and is composed of 5 subunits (alpha, beta, gamma, delta, epsilon), while the F0 ATPase complex is the membrane-embedded proton channel that is composed of at least 3 subunits (A-C), with additional subunits in mitochondria. Both the F1 and F0 complexes are rotary motors that are coupled back-to-back. In the F1 complex, the central gamma subunit forms the rotor inside the cylinder made of the alpha(3)beta(3) subunits, while in the F0 complex, the ring-shaped C subunits forms the rotor. The two rotors rotate in opposite directions, but the F0 rotor is usually stronger, using the force from the proton gradient to push the F1 rotor in reverse in order to drive ATP synthesis [
]. These ATPases can also work in reverse in bacteria, hydrolysing ATP to create a proton gradient.The G subunit is a subunit of the F0 complex in mitochondria; its function is not established yet.
This group represents phosphatases related to PHOSPHO1 and PHOSPHO2 [
]. It includes plant phosphatases with homology to the haloacid dehalogenase (HAD) superfamily [,
]. PHOSPHO1 is a phosphoethanolamine/phosphocholine phosphatase [], while PHOSPHO2 has high activity toward pyridoxal 5'-phosphate (PLP), and it is active at much lower level toward pyrophosphate, phosphoethanolamine (PEA)and phosphocholine (PCho) [].
HAD hydrolase, subfamily IA, Pyridoxal phosphate phosphatase-like
Type:
Family
Description:
The Haloacid Dehalogenase (HAD) superfamily is defined by the presence of three short catalytic motifs [
]. The subfamilies are defined [] based on the location and the observed or predicted fold of a so-called capping domain [], or the absence of such a domain. Subfamily I consists of sequences in which the capping domain is found in between the first and second catalytic motifs. Subfamily II consists of sequences in which the capping domain is found between the second and third motifs. Subfamily III sequences have no capping domain in either of these positions.The Subfamily IA and IB capping domains are predicted by PSI-PRED to consist of an alpha helical bundle. Subfamily IA and IB are separated based on an apparent phylogenetic bifurcation. This group of sequences belong to the IB subfamily of the haloacid dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases.
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 theribosome 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 L28e forms part of the 60S ribosomal subunit [
]. This family is found in eukaryotes. In rat there are 9 or 10 copies of the L28 gene. The L28 protein contains a possible internal duplication of 9 residues [].
This domain consists of 4 beta strands and two alpha helices which make up the dimerisation surface of members of the MEROPS peptidase family M20 []. This family includes a range of zinc exopeptidases: carboxypeptidases, dipeptidases and specialised aminopeptidases [].
This group of proteins contains the metallopeptidases and non-peptidase homologues (amidohydrolases) that belong to the MEROPS peptidase family M20 (clan MH) [
]. The peptidases of this clan have two catalytic zinc ions at the active site, bound by His/Asp, Asp, Glu, Asp/Glu and His. The catalysed reaction involves the release of an N-terminal amino acid, usually neutral or hydrophobic, from a polypeptide []. The peptidase M20 family has four subfamilies:M20A - type example, glutamate carboxypeptidase from Pseudomonas sp. RS16 (
)
M20B - type example, peptidase T from Escherichia coli (
)
M20C - type example, X-His dipeptidase from E. coli (
)
M20D - type example, carboxypeptidase Ss1 from Sulfolobus solfataricus (
)
Homologues from the family that are not peptidases include:Acetylornithine deacetylase, which releases an acetyl group and L-ornithine from N(2)-acetyl-L-ornithine [
]
N-acetyldiaminopimelate deacetylase, which catalyses the conversion of N-acetyl-diaminopimelate to diaminopimelate and acetate [
]
N-carbamoyl-L-amino-acid hydrolase, which converts D,L-5-monosubstituted hydantoins into D- or L-amino acids [
]
Aminoacylase-1, which hydrolyses N-acylated or N-acetylated amino acids [
]
Succinyl-diaminopimelate desuccinylase (
), which catalyses the hydrolysis of N-succinyl-L,L-diaminopimelic acid, forming succinate and LL-2,6-diaminoheptanedioate (DAP, a component of bacterial cell walls) [
]
This entry represents a clade of the amidohydrolases. They classified as metallopeptidases belonging to MEROPS peptidase family M20 (clan MH), subfamily M20D. Included within this group are hydrolases of hippurate (N-benzylglycine), indoleacetic acid (IAA) N-conjugates of amino acids, N-acetyl-L-amino acids and aminobenzoylglutamate. These hydrolases are of the carboxypeptidase-type, most likely utilizing a zinc ion in the active site.In higher plants, the growth hormone indole-3-acetic acid (IAA or auxin) is stored conjugated to sugar moieties via an ester linkage or to amino acids or peptides via an amide. More than 95% of the hormone in a plant can be found in the conjugated form, leaving only a small amount of free hormone available to stimulate and control cellular growth. The overall levels of active IAA in a plant can be controlled not only by the amount of IAA synthesized, but also by the quantity of IAA that is released from the conjugated state into the free state. Amidohydrolases cleave the amide bond between the auxin and the conjugated amino acid. Several IAA amidohydrolases have been isolated from Arabidopsis thaliana (Mouse-ear cress), each of these enzymes has different substrate specificities. The A. thaliana IAA amidohydrolase, IAR3, is able to cleave IAA-Alanine, while products of the other amidohydrolase genes, known as the ILR1-like family of hydrolases (ILR1, ILL1, ILL2, ILL3, and ILL5), cleave primarily IAA-Phenylalanine and IAA-Leucine [
].
Transmembrane protein 135 (TMEM135) is a multi-pass membrane protein. It may be involved in fat storage and longevity regulation in Caenorhabditis elegans [
].
This entry represents a family of conserved proteins found from nematodes to humans. Cytochrome c oxidase assembly protein Pet191 carries six highly conserved cysteine residues. Pet191 is required for the assembly of active cytochrome c oxidase but does not form part of the final assembled complex [
].
This entry represents uroporphyrinogen decarboxylase (URO-D or HemE), which catalyzes the fifth step in the haem biosynthetic pathway, converting uroporphyrinogen III to coproporphyrinogen III by decarboxylating the four acetate side chains of the substrate [
]. This step takes the pathway toward protoporphyrin IX, a common precursor of both haem and chlorophyll, rather than toward precorrin 2 and its products.This activity is essential in all organisms, and subnormal activity of URO-D leads to the most common form of porphyria in humans, porphyria cutanea tarda (PCT) as well as hepatoerythropoietic porphyria (HEP) [
].
Uroporphyrinogen decarboxylase (URO-D), the fifth enzyme of the haem biosynthetic pathway, catalyses the sequential decarboxylation of the four acetyl side chains of uroporphyrinogen to yield coproporphyrinogen [
]. URO-D deficiency is responsible for the human genetic diseases familial porphyria cutanea tarda (fPCT) and hepatoerythropoietic porphyria (HEP). The sequence of URO-D has been well conserved throughout evolution. The best conserved region is located in the N-terminal section; it contains a perfectly conserved hexapeptide. There are two arginine residues in this hexapeptide which could be involved in the binding, via salt bridges, to the carboxyl groups of the propionate side chains of the substrate.The crystal structure of human uroporphyrinogen decarboxylase shows it as comprised of a single domain containing a (beta/alpha)8-barrel with a deep active site cleft formed by loops at the C-terminal ends of the barrel strands.
URO-D is a dimer in solution. Dimerisation juxtaposes the active site clefts of the monomers, suggesting a functionally important interaction between the catalytic centres [].
Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP. There are several different types of transmembrane ATPases, which can differ in function (ATP hydrolysis and/or synthesis), structure (e.g., F-, V- and A-ATPases, which contain rotary motors) and in the type of ions they transport [
,
]. The different types include:F-ATPases (ATP synthases, F1F0-ATPases), which are found in mitochondria, chloroplasts and bacterial plasma membranes where they are the prime producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts).V-ATPases (V1V0-ATPases), which are primarily found in eukaryotes and they function as proton pumps that acidify intracellular compartments and, in some cases, transport protons across the plasma membrane [
]. They are also found in bacteria [].A-ATPases (A1A0-ATPases), which are found in Archaea and function like F-ATPases, though with respect to their structure and some inhibitor responses, A-ATPases are more closely related to the V-ATPases [
,
].P-ATPases (E1E2-ATPases), which are found in bacteria and in eukaryotic plasma membranes and organelles, and function to transport a variety of different ions across membranes.E-ATPases, which are cell-surface enzymes that hydrolyse a range of NTPs, including extracellular ATP.P-ATPases (also known as E1-E2 ATPases) ([intenz:3.6.3.-]) are found in bacteria and in a number of eukaryotic plasma membranes and organelles []. P-ATPases function to transport a variety of different compounds, including ions and phospholipids, across a membrane using ATP hydrolysis for energy. There are many different classes of P-ATPases, which transport specific types of ion: H+, Na
+, K
+, Mg
2+, Ca
2+, Ag
+and Ag
2+, Zn
2+, Co
2+, Pb
2+, Ni
2+, Cd
2+, Cu
+and Cu
2+. P-ATPases can be composed of one or two polypeptides, and can usually assume two main conformations called E1 and E2.This group describes the magnesium translocating P-type ATPase found in a limited number of bacterial species and best described in Salmonella typhimurium, which contains two isoforms [
]. These transporters are active in low external Mg2+ concentrations and pump the ion into the cytoplasm. The magnesium ATPases have been classified as type IIIB by a phylogenetic analysis [].
Gamma-glutamyl hydrolase (GH) is a lysosomal and secreted glycoprotein that hydrolyses the gamma-glutamyl tail of antifolate and folate polyglutamates. Tumour cells that have high levels of GH are inherently resistant to classical antifolates, and further resistance can be acquired by elevations in GH following exposure to this class of anti-tumour agents. The highest level of expression in normal tissues occurs in the liver and kidney in humans. GH is a low-affinity (micromolar), high-turnover enzyme that has a cysteine at the active site. GH is being evaluated as an intracellular target for inhibition in order to enhance the therapeutic activity of antifolates and fluorouracil [
].The 3-dimensional structure of GH shows a central eight-stranded β-sheet, which is sandwiched by three and five α-helices on each side (see []. The fold resembles that of glutamine amidotransferases (GATase) of class I, which are characterised by a conserved Cys-His-Glu active site. The major differences consist of extensions in four loops and at the C terminus of GGH. The active site residues are well conserved and the catalytically essential cysteine, positioned at a nucleophile elbow, suggests that GGH is a cysteine peptidase.
POLD3 is a component of the trimeric and tetrameric DNA polymerase delta complexes (Pol-delta3 and Pol-delta4, respectively), plays a role in high fidelity genome replication, including in lagging strand synthesis, and repair. It is required for optimal Pol-delta activity [
,
,
,
,
].
ALG2 mannosylates Man2GlcNAc(2)-dolichol diphosphate and Man1GlcNAc(2)-dolichol diphosphate to form Man3GlcNAc(2)-dolichol diphosphate [].Defects in ALG2 are the cause of congenital disorder of glycosylation type 1I (CDG1I). CDGs are a family of severe inherited diseases caused by a defect in protein N-glycosylation. They are characterised by under-glycosylated serum proteins [
].
The 26S proteasome is an enzymatic complex that degrades ubiquitinated proteins in eukaryotic cells. 26S proteasome non-ATPase regulatory subunit 5 (PSMD5) is one of a number of chaperones that are involved in the assembly of the proteasome. The chaperones dissociate before 26S proteasome formation is complete [
].TNF-alpha/NFkB inhibits 26S proteasome assembly via abnormal expression
of PSMD5, establishing a link between inflammation and chronic neurodegenerativediseases with altered ubiquitin-proteasome system function [
].
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 bacterial (and chloroplast) examples of the ribosomal small subunit protein S20. Bacterial ribosomal protein S20 forms part of the 30S ribosomal subunit, and interacts with 16S rRNA.
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 low molecular weight transmembrane protein PsbY found in PSII. In higher plants, two related PsbY proteins exist, PsbY-1 and PsbY-2, which appear to function as a heterodimer. In spinach and Arabidopsis, these two proteins arise from a single-copy nuclear gene that is processed in the chloroplast. By contrast, prokaryotic and organellar chromosomes encode a single PsbY protein, as found in cyanobacteria and red algae, indicating a duplication event in the evolution of higher plants [
]. PsbY has two low manganese-dependent activities: a catalase-like activity and an L-arginine metabolising activity that converts L-arginine into ornithine and urea []. In addition, a redox-active group is thought to be present in the protein. In cyanobacteria, PsbY deletion mutants have a slightly impaired PSII that is less capable of coping with low levels of calcium ions than the wild-type.
This family consists of several eukaryotic Sin3 associated polypeptide p18 (SAP18) sequences. SAP18 is known to be a component of the Sin3-containing complex, which is responsible for the repression of transcription via the modification of histone polypeptides [
]. SAP18 is also present in the ASAP complex which is thought to be involved in the regulation of splicing during the execution of programmed cell death [].
This group of DEAD-box RNA helicases includes Dbp10 from fungi, DDX54 (also known as DP97) from mammals and RH29 from plants. DDX54 interacts in a hormone-dependent manner with nuclear receptors [
,
]. It plays an important role in central nervous system myelination []. Dbp10 has a role in ribosome biogenesis []. RH29 is essential for the functional maturation of both male and female gametophytes [].This entry represents the C-terminal domain.
Ribosomal protein L24 is one of the proteins from the large ribosomal subunit. In their mature form, these proteins have 103 to 150 amino-acid residues. Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].
The tubulin heterodimer consists of one alpha- and one beta-tubulin polypeptide. In humans, five tubulin-specific chaperones termed TBCA/B/C/D/E are essential for bring the alpha- and beta-tubulin subunits together into a tightly associated heterodimer. Following the generation of quasi-native beta- and alpha-tubulin polypeptides (via multiple rounds of ATP-dependent interaction with the cytosolic chaperonin), TBCA and TBCB bind to and stabilise newly synthesised beta- and alpha-tubulin, respectively. The exchange of beta-tubulin between TBCA and TBCD, and of alpha-tubulin between TBCB and TBCE, resulting in the formation of TBCD/beta and TBCE/alpha. These two complexes then interact with each other and form a supercomplex (TBCE/alpha/TBCD/beta). Interaction of the supercomplex with TBCC causes the disassembly of the supercomplex and the release of E-site GDP-bound alpha/beta tubulin heterodimer, which becomes polymerization competent following spontaneous exchange with GTP [
].This entry represents tubulin binding cofactor A (TBCA) from animal, plants and fungi. Human TBCA functions as a molecular chaperone for beta-tubulin [
]. Budding yeast TBCA, also known as Rbl2, may bind transiently to free beta-tubulin, which then passes into an aggregated form that is not toxic []. The sequence identity of Rbl2 and human TBCA is only 32%, they appear to be structurally distinct and may interact with beta-tubulin by different mechanisms [].
NOZZLE (also known as SPOROCYTELESS) is a transcription factor that plays a role in patterning the proximal-distal and adaxial-abaxial axes [
,
]. It is an essential factor for ovule development and functions as an adaptor-like transcriptional repressor, recruiting TPL/TPR co-repressors to inhibit TCP transcription factors [].
5'-3'-exoribonucleases are enzymes that degrade RNA by removing terminal nucleotides from the 5' end. Hydrolytic exoribonucleases, to which this entry belongs, produce nucleotide monosphosphates. An exosome and a 5'-3'-exoribonuclease are important in the degradation of very unstable transcripts [
].This entry includes 5'-3'exoribonuclease type 2 (Xrn2, also known as Rat1), which occurs in animal, plant and fungal lineages. They act as post-transcriptional gene silencing (PTGS) suppressors [
]. In Saccharomyces cerevisiae, Rat1 serves to terminate RNA polymerase II (RNAPII) molecules engaged in the production of uncapped RNA []. This entry also includes plant Xrn3 and Xrn4.
In a few bacterial P450-containing systems, the transfer of electrons from
flavoprotein reductase to P450 is mediated by 3Fe-4S ferredoxins [,
,
]. Despite functional similarity of such ferredoxins tothe adrenodoxin family, they do not share sequence similarity but seem to be
similar to some mono-[4Fe-4S]cluster ferredoxins but lack the fourth cysteine
residue conserved in 4Fe-4S sequences []. It has been shownexperimentally that the 4Fe-4S cluster of related ferredoxins from archaebacteria
easily converts to a 3Fe-4S cluster [].
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 [].
The microbial degradation of cellulose and xylans requires several types of
enzyme such as endoglucanases (EC 3.2.1.4), cellobiohydrolases (EC 3.2.1.91)(exoglucanases), or xylanases (EC 3.2.1.8) [
]. Structurally, cellulases and xylanases generally consist of a catalytic domain and a conserved region of ~100 amino acid residues, the carbohydrate-binding module 2 (CBM2) []. It is found either at the N-terminal or at the C-terminal extremity of these enzymes.CBM2 can be classified in 2 subfamilies according to substrate specificities:
CBM2a which binds cellulose and CBM2b which interacts specifically with xylan. Like other CBM domains CBM2 is a β-sheet domain containing a planar facewhich interacts with its ligand via a hydrophobic strip of aromatic residues [
]. In family 2a this hydrophobic surface consists of threetryptophan residues, which are all required for binding soluble and insoluble
forms of cellulose []. In family 2b only 2 surface-exposed tryptophans areconserved and the first one is oriented differently. It is therefore not well
oriented to interact with cellulose but is ideal for binding xylan [].This entry recognises both CBM2 subfamilies.
In plants, this family is involved in mitochondrial fission. It binds to dynamin-related proteins and plays a role in their relocation from the cytosol to mitochondrial fission sites [
]. Its function in bacteria is unknown.
This domain is found towards the C-terminal of BCAS3 and ATG18-like proteins from plants. In BCAS3, this domain seems to be important for PHAF1 interactions [
].This entry includes BCAS3 from animals and AT18F/G/H from Arabidopsis. BCAS3 is a microtubule associated cell migration factor that has been linked to the development of breast cancer and angiogenesis [
]. It forms a complex with PHAF1 and associates with the preautophagosomal structure during both non-selective and selective autophagy [].AT18F/G/H are linked to autophagy [
].
Bridge-like lipid transfer protein family member 3A/B
Type:
Family
Description:
This family consists of bridge-like lipid transfer protein family member 3a/B (also known as UHRF1-binding protein 1 and 1-like proteins. These are tube-forming lipid transport proteins which mediate the transfer of lipids between membranes at organelle contact sites [
], and they are required for retrograde traffic of vesicle clusters in the early endocytic pathway to the Golgi complex [,
].
The chaperonins are 'helper' molecules required for correct folding and subsequent assembly of some proteins [
]. These are required for normal cell growth [], and are stress-induced, acting to stabilise or protect disassembled polypeptides under heat-shock conditions. Type I chaperonins present in eubacteria, mitochondria and chloroplasts require the concerted action of 2 proteins, chaperonin 60 (cpn60) and chaperonin 10 (cpn10) []. The 10kDa chaperonin (cpn10 - or groES in bacteria) exists as a ring-shaped oligomer of between six to eight identical subunits, while the 60kDa chaperonin (cpn60 - or groEL in bacteria) forms a structure comprising 2 stacked rings, each ring containing 7 identical subunits [
]. These ring structures assemble by self-stimulation in the presence of Mg2+-ATP. The central cavity of the cylindrical cpn60 tetradecamer provides as isolated environment for protein folding whilst cpn-10 binds to cpn-60 and synchronizes the release of the folded protein in an Mg
2+-ATP dependent manner [
]. The binding of cpn10 to cpn60 inhibits the weak ATPase activity of cpn60.Escherichia coli GroES has also been shown to bind ATP cooperatively, and with an affinity comparable to that of GroEL []. Each GroEL subunit contains three structurally distinct domains: an apical, an intermediate and an equatorial domain. The apical domain contains the binding sites for both GroES and the unfolded protein substrate. The equatorial domain contains the ATP-binding site and most of the oligomeric contacts. The intermediate domain links the apical and equatorial domains and transfers allosteric information between them. The GroEL oligomer is a tetradecamer, cylindrically shaped, that is organised in two heptameric rings stacked back to back. Each GroEL ring contains a central cavity, known as the 'Anfinsen cage', that provides an isolated environment for protein folding. The identical 10kDa subunits of GroES form a dome-like heptameric oligomer in solution. ATP binding to GroES may be important in charging the seven subunits of the interacting GroEL ring with ATP, to facilitate cooperative ATP binding and hydrolysis for substrate protein release.
Cpn20 is a functional homologue of the cpn10 (also known as GroES) co-chaperonin, but it consists of two cpn10-like units joined head-to-tail by a short chain of amino acids. This double protein is unique to plastids and was shown to exist in plants as well plastid-containing parasites [
]. Cpn20 seems to function as a co-chaperone, along with cpn60, and in certain cases is essential for the discharge of biologically active proteins from cpn60 []. It might be an iron chaperone for superoxide dismutase in activating iron superoxide dismutase (FeSOD) [].
A number of different families of proteins share a conserved domain which was first characterised in some animal lectins and which seem to function as a calcium-dependent carbohydrate-recognition domain [
,
]. This domain, which is known as the C-type lectin domain (CTL) or as the carbohydrate-recognition domain (CRD), consists of about 110 to 130 residues. There are four cysteines which are perfectly conserved and involved in two disulphide bonds.There are proteins with modules similar in overall structure to CRDs that serve functions other than sugar binding. Therefore, a more general term C-type lectin-like domain was introduced to refer to such domains, although both terms C-type lectin and C-type lectin-like are sometimes used interchangeably [
].C-type lectins can be further divided into seven subgroups based on additional non-lectin domains and gene structure: (I) hyalectans, (II) asialoglycoprotein receptors, (III) collectins, (IV) selectins, (V) NK group transmembrane receptors, (VI) macrophage mannose receptors, and (VII) simple (single domain) lectins [
]. Lectins are a diverse group of proteins, both in terms of structure and activity. Carbohydrate binding ability may have evolved independentlyand sporadically in numerous unrelated families, where each evolved a structure that was conserved to fulfil some other activity and function. In general, animal lectins act as recognition molecules within the immune system, their functions involving defence against pathogens, cell trafficking, immune regulation and the prevention of autoimmunity [
].
Lectins occur in plants, animals, bacteria and viruses. Initially described for their carbohydrate-binding activity [
], they are now recognised as a more diverse group of proteins, some of which are involved in protein-protein, protein-lipid or protein-nucleic acid interactions []. There are at least twelve structural families of lectins, of which C-type (Ca+-dependent) lectins is one. C-type lectins can be further divided into seven subgroups based on additional non-lectin domains and gene structure: (I) hyalectans, (II) asialoglycoprotein receptors, (III) collectins, (IV) selectins, (V) NK group transmembrane receptors, (VI) macrophage mannose receptors, and (VII) simple (single domain) lectins [].This entry represents a structural domain found in C-type lectins, as well as in other proteins, including:The N-terminal domain of aerolysin [
] and the N-terminal domain of the S2/S3 subunit of pertussis toxin [].The C-terminal domain of invasin [
] and intimin [].Link domain, which includes the Link module of TSG-6 [
] (a hyaladherin with important roles in inflammation and ovulation) and the hyaluronan binding domain of CD44 (which contains extra N-terminal β-strand and C-terminal β-hairpin) [
].Endostatin [
] and the endostatin domain of collagen alpha 1 (XV) [], these domains being decorated with many insertions in the common fold.The noncollagenous (NC1) domain of collagen IV, which consists of a duplication of the C-type lectin domain, with segment swapping within and between individual domains [
].Sulphatase-modifying factors (C-alpha-formyglycine-generating enzyme), where the fold is decorated with many additional structures [
,
].The C-terminal domain of the major tropism determinant (Mtd), where the fold is decorated with many additional structures, and has an overall similarity to the sulphatase modifying factor family but lacking the characteristic disulphide [
].
Lectins occur in plants, animals, bacteria and viruses. Initially described for their carbohydrate-binding activity [
], they are now recognised as a more diverse group of proteins, some of which are involved in protein-protein, protein-lipid or protein-nucleic acid interactions []. There are at least twelve structural families of lectins, of which C-type (Ca+-dependent) lectins is one. C-type lectins can be further divided into seven subgroups based on additional non-lectin domains and gene structure: (I) hyalectans, (II) asialoglycoprotein receptors, (III) collectins, (IV) selectins, (V) NK group transmembrane receptors, (VI) macrophage mannose receptors, and (VII) simple (single domain) lectins [].The term 'C-type lectin domain' was introduced to distinguish a carbohydrate-recognition domain (CRD) which is present in all Ca2+-dependent lectins, but not in other types of animal lectins. However, there are proteins with modules similar in overall structure to CRDs that serve functions other than sugar binding. Therefore, a more general term C-type lectin-like domain was introduced to refer to such domains, although both terms are sometimes used interchangeably [
].This superfamily represents a structural domain found in C-type lectins, as well as in other proteins, including:The C-terminal domain of invasin [
] and intimin [].Link domain, which includes the Link module of tumor necrosis factor-inducible gene 6 protein (TSG-6) [
] (a hyaladherin with important roles in inflammation and ovulation) and the hyaluronan binding domain of CD44 (which contains extra N-terminal β-strand and C-terminal β-hairpin) []. The Link domain may have emerged as a result of a deletion of the long loop region from an ancestral canonical C-type lectin domain [].Endostatin [
] and the endostatin domain of collagen alpha 1 (XV) [], these domains being decorated with many insertions in the common fold.
This domain is found at the C terminus of Red protein (
). This and related proteins are thought to be localised to the nucleus, and contain a RED repeat which consists of a number of RE and RD sequence elements [
]. The function of Red protein is unknown, but efficient sequestration to nuclear bodies suggests that its expression may be tightly regulated or that the protein self-aggregates extremely efficiently [].
This domain contains sequences that are similar to the N-terminal region of Red protein (
). This and related proteins contain a RED repeat which consists of a number of RE and RD sequence elements [
]. The region in question has several conserved NLS sequences and a putative trimeric coiled-coil region [], suggesting that these proteins are expressed in the nucleus []. Protein RED (also known as IK) is found in the nucleus and is a component of the spliceosome []. It is also associated with the spindle pole where it co-localizes with and interacts with the spindle assembly checkpoint protein MAD1 during metaphase and anaphase. Depletion of RED shortens the mitotic cycle and MAD1 is incorrectly localized [].
Proteins in this family include glycerophosphocholine acyltransferase 1 (GPCAT). GPCAT homologues have been identified in most eukaryotes except chordates, but are not found in prokaryotes. GPCAT can acylate glycero-3-phosphocholine (GPC) with acyl groups from acyl-CoA. Thus it contributes to the maintenance of phosphatidylcholine (PC) homeostasis and may have specific functions in acyl editing of PC [
].
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 [
]. The low molecular weight transmembrane protein PsbX found in PSII is associated with the oxygen-evolving complex. Its expression is light-regulated. PsbX appears to be involved in the regulation of the amount of PSII [
], and may be involved in the binding or turnover of quinone molecules at the Qb (PsbA) site [].
Protein EARLY FLOWERING 4 is a component of the central CCA1/LHY-TOC1 feedback loop in the circadian clock that promotes clock accuracy and is required for sustained rhythms in the absence of daily light/dark cycles [
,
].This domain forms an α-helical homodimer in ELF4 proteins.
The tripartite DENN (after differentially expressed in neoplastic versus
normal cells) domain is found in several proteins involved in Rab-mediatedprocesses or regulation of MAPKs (Mitogen-activated preotein kinases)
signaling pathways. It actually consists of three parts as the original DENNdomain is always encircled on both sides by more divergent domains, called
uDENN (after upstream DENN) and dDENN (for downstream DENN). The tripartiteDENN domain is found associated with other domains, such as RUN, PLAT, PH, PPR, WD-40, GRAM or C1. The function of DENN domain remains to date unclear, although it appears to represent a good candidate for a GTP/GDP exchange activity [
,
].The general characteristics of DENN domains - three regions dDENN, DENNitself, and uDENN having different patterns of sequence conservation and
separated by sequences of variable length - suggest that they are composed ofat least three sub-domains which may feature distinct folds but which are
always associated due to functional and/or structural constraints [].Some proteins known to contain a tripartite DENN domain are listed below:Rat Rab3 GDP/GTP exchange protein (Rab3GEP) Human mitogen-activated protein kinase activating protein containing death
domain (MADD). It is orthologous to Rab3GEP Caenorhabditis elegans regulator of presynaptic activity aex-3, the
ortholog of Rab3GEP Mouse Rab6 interacting protein 1 (Rab6IP1) Human SET domain-binding factor 1(SBF1) Human suppressor of tumoreginicity 5 (ST5) Human C-MYC promoter-binding protein IRLB This entry represents the core or cDENN domain.
The tripartite DENN (after differentially expressed in neoplastic versus
normal cells) domain is found in several proteins involved in Rab-mediatedprocesses or regulation of MAPKs (Mitogen-activated preotein kinases)
signaling pathways. It actually consists of three parts as the original DENNdomain is always encircled on both sides by more divergent domains, called
uDENN (after upstream DENN) and dDENN (for downstream DENN). The tripartiteDENN domain is found associated with other domains, such as RUN, PLAT, PH, PPR, WD-40, GRAM or C1. The function of DENN domain remains to date unclear, although it appears to represent a good candidate for a GTP/GDP exchange activity [
,
].The general characteristics of DENN domains - three regions dDENN, DENNitself, and uDENN having different patterns of sequence conservation and
separated by sequences of variable length - suggest that they are composed ofat least three sub-domains which may feature distinct folds but which are
always associated due to functional and/or structural constraints [].Some proteins known to contain a tripartite DENN domain are listed below:Rat Rab3 GDP/GTP exchange protein (Rab3GEP) Human mitogen-activated protein kinase activating protein containing death
domain (MADD). It is orthologous to Rab3GEP Caenorhabditis elegans regulator of presynaptic activity aex-3, the
ortholog of Rab3GEP Mouse Rab6 interacting protein 1 (Rab6IP1) Human SET domain-binding factor 1(SBF1) Human suppressor of tumoreginicity 5 (ST5) Human C-MYC promoter-binding protein IRLB This entry represents the uDENN domain.
The tripartite DENN (after differentially expressed in neoplastic versus
normal cells) domain is found in several proteins involved in Rab-mediatedprocesses or regulation of MAPKs (Mitogen-activated preotein kinases)
signaling pathways. It actually consists of three parts as the original DENNdomain is always encircled on both sides by more divergent domains, called
uDENN (after upstream DENN) and dDENN (for downstream DENN). The tripartiteDENN domain is found associated with other domains, such as RUN, PLAT, PH, PPR, WD-40, GRAM or C1. The function of DENN domain remains to date unclear, although it appears to represent a good candidate for a GTP/GDP exchange activity [
,
].The general characteristics of DENN domains - three regions dDENN, DENNitself, and uDENN having different patterns of sequence conservation and
separated by sequences of variable length - suggest that they are composed ofat least three sub-domains which may feature distinct folds but which are
always associated due to functional and/or structural constraints [].Some proteins known to contain a tripartite DENN domain are listed below:Rat Rab3 GDP/GTP exchange protein (Rab3GEP) Human mitogen-activated protein kinase activating protein containing death
domain (MADD). It is orthologous to Rab3GEP Caenorhabditis elegans regulator of presynaptic activity aex-3, the
ortholog of Rab3GEP Mouse Rab6 interacting protein 1 (Rab6IP1) Human SET domain-binding factor 1(SBF1) Human suppressor of tumoreginicity 5 (ST5) Human C-MYC promoter-binding protein IRLB This entry represents the dDENN domain.
DNA recombination and repair protein RecA, C-terminal
Type:
Homologous_superfamily
Description:
The recA gene product is a multifunctional enzyme that plays a role in homologous recombination, DNA repair and induction of the SOS response [
]. In homologous recombination, the protein functions as a DNA-dependent ATPase, promoting synapsis, heteroduplex formation and strand exchange between homologous DNAs []. RecA also acts as a protease cofactor that promotes autodigestion of the lexA product and phage repressors. The proteolytic inactivation of the lexA repressor by an activated form of recA may cause a derepression of the 20 or so genes involved in the SOS response, which regulates DNA repair, induced mutagenesis, delayed cell division and prophage induction in response to DNA damage []. RecA is a protein of about 350 amino-acid residues. Its sequence is very well conserved [
,
,
] among eubacterial species. It is also found in the chloroplast of plants []. RecA-like proteins are found in archaea and diverse eukaryotic organisms, like fission yeast, mouse or human. In the filamentvisualised by X-ray crystallography, β-strand 3, the loop C-terminal to β-strand 2, and α-helix D of the core domain form one surface that packs against α-helix A and β-strand 0 (the N-terminal domain) of an adjacent monomer during polymerisation [
]. The core ATP-binding site domain is well conserved, with 14 invariant residues. It contains the nucleotide binding loop between β-strand 1 and α-helix C. The Escherichia coli sequence GPESSGKT matches the consensus sequence of amino acids (G/A)XXXXGK(T/S) for the Walker A box (alsoreferred to as the P-loop) found in a number of nucleoside triphosphate (NTP)-binding proteins. Another
nucleotide binding motif, the Walker B box is found at β-strand 4 in the RecA structure. The Walker Bbox is characterised by four hydrophobic amino acids followed by an acidic residue (usually aspartate). Nucleotide specificity and additional ATP binding interactions are contributed by the amino acid residues at β-strand 2 and the loop C-terminal to that
strand, all of which are greater than 90% conserved among bacterial RecA proteins.This superfamily represents the C-terminal domain, which forms an alpha/beta two layer sandwich [
].
Glycylpeptide N-tetradecanoyltransferase, also known as Myristoyl-CoA:protein N-myristoyltransferase (
) (Nmt), is the enzyme responsible for transferring a myristate group on the N-terminal glycine of a number of cellular eukaryotics and viral proteins [
]. Nmt is a monomeric protein of about 50 to 60kDa whose sequence appears to be well conserved. In Drosophila, this protein is critical for the developmental processes that involve cell shape changes and movement [].
Glycylpeptide N-tetradecanoyltransferase, conserved site
Type:
Conserved_site
Description:
Glycylpeptide N-tetradecanoyltransferase, also known as Myristoyl-CoA:protein N-myristoyltransferase (
) (Nmt), is the enzyme responsible for transferring a myristate group on the N-terminal glycine of a number of cellular eukaryotics and viral proteins [
]. Nmt is a monomeric protein of about 50 to 60kDa whose sequence appears to be well conserved. In Drosophila, this protein is critical for the developmental processes that involve cell shape changes and movement [].Two highly conserved regions are found. The first one is located in the central section, the second in the C-terminal part.
Glycylpeptide N-tetradecanoyltransferase, also known as Myristoyl-CoA:protein N-myristoyltransferase (
) (Nmt), is the enzyme responsible for transferring a myristate group on the N-terminal glycine of a number of cellular eukaryotics and viral proteins [
]. Nmt is a monomeric protein of about 50 to 60kDa whose sequence appears to be well conserved. In Drosophila, this protein is critical for the developmental processes that involve cell shape changes and movement [].The N and C-terminal domains of NMT are structurally similar, each adopting an acyl-CoA N-acyltransferase-like fold. This entry represents the C-terminal region [
].
Diacylglycerol O-acyltransferase 1 (DGAT1) catalyses the final step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates. In plants, diacylglycerol O-acyltransferase 1 (DGAT1, TAG1) is a major enzyme for oil accumulation in seeds. It has complementary functions with PDAT1 acyltransferase that are essential for triacylglycerol synthesis and normal development of both seeds and pollen [
,
,
,
,
].In mammals, DGAT1 is a multifunctional acyltransferase capable of synthesizing diacylglycerol, retinyl, and wax esters in addition to triacylglycerol [
]. In liver, it plays a role in esterifying exogenous fatty acids to glycerol []. It also functions as the major acyl-CoA retinol acyltransferase in the skin, where it acts to maintain retinoid homeostasis and prevent retinoid toxicity leading to skin and hair disorders [].
This domain can be found in the C terminus of the SERRATE (SE) from plants and its homologue, Ars2, from animals. They play a role in nuclear RNA metabolism. They interact with the nuclear cap-binding complex (CBC) and mediates interactions with diverse RNA processing and transport machineries in a transcript-dependent manner. Interestingly, the plant SERRATE does not have the RNA recognition motif (RRM) domain found in metazoans and S. pombe [
].
RNA polymerases catalyse the DNA dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). Domain 4 is also known as the external 2 domain [
].
RNA polymerases catalyse the DNA dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). Domain 5 is also known as the external 2 domain [
].
This entry includes translation machinery-associated protein 22 (Tma22) from yeasts and density-regulated protein (DENR) from animals. DENR may be involved in the translation of target mRNAs by scanning and recognition of the initiation codon [
]. DENR and MCT-1 form a heterodimer, which binds to the ribosome and is involved in unconventional translation initiation, reinitiation, and recycling [].
Saccharomyces cerevisiae A49 is a specific subunit associated with RNA polymerase I (Pol I) in eukaryotes. Pol I maintains transcription activities in A49 deletion mutants. However, such mutants are deficient in transcription activity at low temperatures. Deletion analysis of the fusion yeast homologue indicates that only the C-terminal two thirds are required for function. Transcript analysis has demonstrated that A49 is maximising transcription of ribosomal DNA [
].
CLEC16A (C-Type Lectin Domain Containing 16A) has an inhibitory role in autophagy, probably by activating the mTOR pathway [
]. It also has a role in beta-cells as a regulator of mitophagy [].GFS9/TT9 (TRANSPARENT TESTA 9) is a protein from Arabidopsis required for vacuolar development through membrane fusion at vacuoles. It contributes to intracellular membrane trafficking and flavonoid accumulation [
].This entry represents a domain found at the N terminus of CLEC16A and GFS9/TT9.
Inositol oxygenase (
) is involved in the biosynthesis of UDP-glucuronic acid (UDP-GlcA), providing nucleotide sugars for cell-wall polymers. It may be also involved in plant ascorbate biosynthesis [
,
].
This SM domain is found in Ataxin-2 [
,
]. This domain has been shown to interact with RNA helicase DDX6 [].Ataxin-2 has many functions, such as endocytic receptor cycling [
], translational regulation, embryonic development [], energy metabolism and weight regulation []. Mutations of the Ataxin-2 gene cause spinocerebellar ataxia 2 (SCA2), a neurodegenerative disorder leading to predominant loss of Purkinje cells in the cerebellum and impairment of motor coordination []. In SCA2, expansion of a CAG repeat in exon 1 of the Ataxin-2 (ATXN2) gene causes expansion of a polyQ domain in the ATXN2 protein []. ATXN2 has been shown to interact with many proteins. It interacts with multiple RNA-binding proteins (RBPs), staufen, IP3R, RGS8 mRNA, endophilins and CIN85 [].
This domain can be found in eukaryotic ataxin-2 [
]. Ataxin-2 is predicted to consist of mostly non-globular domains []. This domain has been shown to interact with RNA helicase DDX6 [].Ataxin-2 has many functions, such as endocytic receptor cycling [
], translational regulation, embryonic development [], energy metabolism and weight regulation []. Mutations of the Ataxin-2 gene cause spinocerebellar ataxia 2 (SCA2), a neurodegenerative disorder leading to predominant loss of Purkinje cells in the cerebellum and impairment of motor coordination [
]. In SCA2, expansion of a CAG repeat in exon 1 of the Ataxin-2 (ATXN2) gene causes expansion of a polyQ domain in the ATXN2 protein []. ATXN2 has been shown to interact with many proteins. It interacts with multiple RNA-binding proteins (RBPs), staufen, IP3R, RGS8 mRNA, endophilins and CIN85 [].Proteins containing this domain also include Pbp1 from budding yeasts, Pbp1 interacts with Pab1 to regulate mRNA polyadenylation [
,
]. It promotes mating-type switching in mother cells by positively regulating HO mRNA translation [] and forms a condensate in response to respiratory status to regulate TORC1 signaling []. It is also involved in P-body-dependent granule assembly [].
This entry represents the anoctamin family, which includes anoctamin1-10 (Ano1-10 or TMEM16A-J); 7 members could be divided into two subfamilies, Ca(2+)-dependent Cl(-) channels (TMEM16A and 16B) and Ca(2+)-dependent lipid scramblases (TMEM16C, 16D, 16F, 16G, and 16J) [
]. This entry also includes anoctamin-like protein At1g73020 from Arabidopsis and increased sodium tolerance protein 2 (Ist2) from budding yeasts. Ano1 and Ano2 (also known as TMEM16A and TMEM16B) are calcium-activated chloride channels (CaCC), which play a role in transepithelial anion transport and smooth muscle contraction [
,
]. Ano3-10 do not exhibit calcium-activated chloride channel (CaCC) activity [,
]. Ist2 may be involved in ion homeostasis together with BTN1 or BTN2 [
].
The trafficking protein particle complex TRAPP is a multi-protein complex needed in the early stages of the secretory pathway. To date, two kinds of TRAPP complexes have been studied, TRAPPI and TRAPP II. These complexes differ in subunit composition [
]. TRAPP I binds vesicles derived from the endoplasmic reticulum bringing them closer to the acceptor membrane. This entry represents a domain which forms part of the TRAPP complex for mediating vesicle docking and fusion in the Golgi apparatus. The fungal version is referred to as Trs130, and an alternative vertebrate alias is TMEM1 [
,
].
Members of this eukaryotic family are part of the group II chaperonin complex called CCT (chaperonin containing TCP-1 or Tailless Complex Polypeptide 1) or TRiC [
,
]. Chaperonins are involved in productive folding of proteins []. They share a common general morphology, a double toroid of 2 stacked rings. The archaeal equivalent group II chaperonin is often called the thermosome []. Both the thermosome and the TCP-1 family of proteins are weakly, but significantly [], related to the cpn60/groEL chaperonin family (see ).
The TCP-1 protein was first identified in mice where it is especially abundant in testis but present in all cell types. It has since been found and characterised in many other animal species, as well as in yeast, plants and protists. The TCP1 complex has a double-ring structure with central cavities where protein folding takes place [
]. TCP-1 is a highly conserved protein of about 60kDa (556 to 560 residues) which participates in a hetero-oligomeric 900kDa double-torus shaped particle [] with 6 to 8 other different, but homologous, subunits []. These subunits, the chaperonin containing TCP-1 (CCT) subunit beta, gamma, delta, epsilon, zeta and eta are evolutionary related to TCP-1 itself [,
]. Non-native proteins are sequestered inside the central cavity and folding is promoted by using energy derived from ATP hydrolysis [,
,
]. The CCT is known to act as a molecular chaperone for tubulin, actin and probably some other proteins [,
].
This family consists exclusively of the CCT alpha subunit (part of a paralogous family) from animals, plants, fungi, and other eukaryotes.
GINS is a key component of eukaryotic replicative forks. It is part of the CMG (Cdc45-MCM-GINS) complex, the eukaryotic replicative helicase that unwinds double-stranded DNA at replication forks [
]. Beside its role as a key component of the CMG complex, GINS mediates a interactions with many replication factors [,
].GINS is composed of four subunits: Sld5, Psf1, Psf2, and Psf3 [
]. The four subunits are structurally related and are likely to derive from a single protein. They share a common fold made up of an α-helical A domain and a beta rich B domain. Sld5 and Psf1 possess the A domain at the N terminus and the B domain at the C terminus, whereas these two domains are swapped in Psf2 and Psf3 []. All subunits are essential for DNA replication.This family of proteins represents the Sld5 subunit.
This conserved domain is found in a family of proteins that function as subunits of transcription factor IIIC (TFIIIC) [
]. TFIIIC in yeast and humans is required for transcription of tRNA and 5 S RNA genes by RNA polymerase III. The yeast proteins in this entry are fused to phosphoglycerate mutase domain.
Vps36 is a subunit of ESCRT-II, a protein complex involved in driving protein sorting from endosomes to lysosomes. The GLUE domain of Vps36 allows for a tight interaction to occur between the protein and Vps28, a subunit of ESCRT-I. This interaction is critical for ubiquitinated cargo progression from early to late endosomes [
]. The multivesicular body (MVB) protein-sorting pathway targets transmembrane
proteins either for degradation or for function in the vacuole/lysosomes. Thesignal for entry into this pathway is monoubiquitination of protein cargo,
which results in incorporation of cargo into luminal vesicles at lateendosomes. Another crucial player is phosphatidylinositol 3-phosphate
(PtdINS(3)P), which is enriched on early endosomes and on the luminal vesiclesof MVBs. The ESCRT complexes are critical for MVB budding and sorting of
monoubiquitinated cargo into the luminal vesicles. Various Ub-binding domains(UBDs), such as UIM, UEV and NZF are found in such
machineries. The Vps 36 subunit of the ESCRT-II trafficking complex binds bothphosphoinositides and ubiquitin. All members of the Vps36 family contain a
divergent GRAM/PH-like domain and yeast and some other fungi have one or twoNZF domains inserted in the GRAM/PH-like domain.The N-terminal region of Vps36 (EAP45) has been named the GLUE (GRAM-like ubiquitin-binding in EAP45)
domain. The GLUE domain acts as a central cog driving the endosomal ESCRTmachinery, through simultaneous interactions with PtdIns3P-containing
membranes, ubiquitin, and ESCRT-I. Like other known ubiquitin-binding domains,the GLUE domain interacts with the hydrophobic surface patch of ubiquitin. TheGLUE domain is the first ubiquitin-binding domain shown to bind
phosphoinositides, and the ability of the same domain to bind both ubiquitinand a phosphoinositide opens interesting possibilities for coordination of
membrane interactions and cargo recognition [,
,
,
,
].The GLUE domain has a split PH-domain fold with two curved beta sheets and
one long alpha helix. The two sheets (beta1-beta4 and beta5-beta7) form a beta barrel-like structure, the C-terminal alpha helix is wedged
between the two beta sheets, covering a hydrophobic core. The Vps36 GLUEdomain binds PtdIns3P via a positively charged lipid binding pocket,
delineated by the variable loops beta1/beta2, beta5/beta6 and beta7/alpha1, incontrast to the vast majority of characterised PH domains, which use a
different lipid binding pocket [,
].
This family consists of defensin-like proteins from plants. Plant genomes contain several hundred defensin-like (DEFL) genes that encode short cysteine-rich proteins resembling defensins, which are known antimicrobial polypeptides [
]. Arabidopsis thaliana has more than 300 DEFL genes, and they are likely to be involved in both natural immunity and cell-to-cell communication, including pollen-pistil interactions [].
In budding yeasts, Paf1 is part of the Paf1 complex, an RNA polymerase II-associated protein complex containing Paf1, Cdc73, Ctr9, Rtf1 and Leo1 [
]. Paf1 complex is involved in histone modifications, transcription elongation and other gene expression processes that include transcript site selection []. This entry also includes Paf1 homologues from animals and plants. Human Paf1, also known as PD2 (pancreatic differentiation 2), is associated with tumorigenesis [
]. Human Paf1 complex (Paf1C) consists of Paf1, Cdc73, Ctr9, Rtf1, Leo1 and Wdr61 (Ski8). As in yeast, the human Paf1C has a central role in co-transcriptional histone modifications []. Human Paf1 complex has a crucial role in the antiviral response []. Arabidopsis Paf1C related proteins such as VIP4 (Leo1), VIP5 (Rtf1), ELF7 (Paf1), ELF8 (Ctr9) and ATXR7 (Set1) are required for the induction of seed dormancy. They control both germination and flowering time [
].
Members of this group are poly(A) polymerases (polynucleotide adenylyltransferases, PAP,
). In eukaryotes, polyadenylation of pre-mRNA plays an essential role in the initiation step of protein synthesis, as well as in the export and stability of mRNAs. Poly(A) polymerase, the central enzyme of the polyadenylation machinery, is a template-independent RNA polymerase that specifically incorporates ATP at the 3' end of mRNA [
,
].The catalytic domain of poly(A) polymerase shares substantial structural homology with other nucleotidyl transferases such as DNA polymerase beta and kanamycin transferase [
]. The three invariant aspartates of the catalytic triad ligate two of the three active site metals. One of these metals also contacts the adenine ring. Other conserved, catalytically important residues contact the nucleotide. These contacts, taken together with metal coordination of the adenine base, provide a structural basis for ATP selection by poly(A) polymerase [].The central domain of poly(A) polymerase shares structural similarity with the allosteric activity domain of ribonucleotide reductase R1, which comprises a four-helix bundle and a three-stranded mixed β-sheet. Even though the two enzymes bind ATP, the ATP-recognition motifs are different [
]. The C-terminal domain is predicted to be an RNA-binding domain because it folds into a compact domain reminiscent of the RNA-recognition motif fold [].The C-terminal region beyond the predicted RNA-binding domain is only conserved in vertebrates and is dispensable for catalytic activity
in vitro. The extended C-terminal domain of vertebrate PAPs is rich in serines and threonines, and enzyme activity can be down regulated by phosphorylation at multiple sites [
,
]. The extreme C terminus of PAP is also the target for another type of regulation. The U1A protein, a component of the U1 snRNP which functions in 5 splice site recognition, is known to inhibit polyadenylation of its own mRNA by binding to PAP []. The C terminus of PAP is also involved in protein-protein interactions with the splicing factor U2AF65 [] and the snRNP protein U1-70K [].
Tubulin tyrosine ligase like 12 (TTLL2) is a member of the tubulin tyrosine ligase (TTL) family. Its function is not clear. It has both SET-like and TTL-like domains, suggesting histone methylation and tubulin tyrosine ligase activities. However, this protein does not have catalytic functions related to tubulin and histone modification, though it seems to have a regulatory role in these processes [
].
Tubulins and microtubules are subjected to several post-translational modifications of the carboxy-terminal end of most major forms of tubulins has been extensively analysed. This modification cycle involves a specific carboxypeptidase and the activity of the tubulin-tyrosine ligase (TTL) and the tubulin polyglutamylase (TTLL) [
,
]. Tubulin-tyrosine ligase (TTL) catalyses the ATP-dependent post-translational addition of a tyrosine to the carboxy terminal end of detyrosinated alpha-tubulin. Tubulin polyglutamylase (such as TTLL10) can modify both tubulin and non-tubulin proteins, generating side chains of glycine on the γ-carboxyl groups of specific glutamate residues of target proteins []. Tubulin polyglutamylation may be involved in the organisation of the neuronal microtubule network, in centriole stability, axoneme motility and mitosis [].
This domain is found in a widespread superfamily known as MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism) [
]. Included in this superfamily are:5-lipoxygenase activating protein (gene FLAP), which seems to be required for the activation of 5-lipoxygenase.Leukotriene C4 synthase (
), which catalyses the production of LTC4 from LTA4.
Microsomal glutathione S-transferase II (
) (GST-II), which also produces LTC4 from LTA4.
Prostaglandin E synthase, which catalyses the synthesis of PGE2 from PGH2 (produced by cyclooxygenase from arachidonic acid). The structure of this domain consists of four transmembrane helices [
].
Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex
Type:
Family
Description:
The pyruvate dehydrogenase complex catalyses the overall conversion of pyruvate to acetyl-CoA and CO2. It contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3) [
]. This entry represent the dihydrolipoamide acetyltransferase (E2) subunit (), also known as Lat1.
The ATPases Associated to a variety of cellular Activities (AAA) are a family distinguished by a highly conserved module of 230 amino acids [
]. The highly conserved nature of this module across taxa suggests that it has a key cellular role. Members of the family are involved in diverse cellular functions including gene expression, peroxisome assembly and vesicle mediated transport. Although the role of this ATPase AAA domain is not, as yet, clear, the AAA+ superfamily of proteins to which the AAA ATPases belong has a chaperone-like function in the assembly, operation or disassembly of proteins []. This ATPase domain includes some proteins not detected by the model.
Some bacterial regulatory proteins activate the expression of genes from
promoters recognised by core RNA polymerase associated with the alternativesigma-54 factor. These have a conserved domain of about 230 residues involved
in the ATP-dependent [,
] interaction with sigma-54. About half of the proteins in which this domain is found (algB, dcdT, flbD, hoxA, hupR1, hydG, ntrC, pgtA and pilR) belong to signal transduction two-component systems [] and possess a domain that can be phosphorylated by a sensor-kinase protein in their N-terminal section. Almost all of these proteins possess a helix-turn-helix DNA-binding domain in their C-terminal section.The domain involved in interaction with the sigma-54 factor has an ATPase activity. This may be required to promote a conformational change necessary for the interaction [
]. The domain contains an atypical ATP-binding motif A (P-loop) as well as a form of motif B. This entry represents a conserved site corresponding to the first ATP-binding motif located in the N-terminal section of the sigma-54 interaction domain.
Voltage-dependent cation (K+, Na+ and Ca2+) channels allow ion conduction in response to changes in cell membrane voltage. This superfamily represents a four helix bundle domain found in voltage-dependent channels [
].
Nuclear cap-binding protein subunit 2 (NCBP2, also known as CBC2 and CBP20) forms the CBC complex with the nuclear cap-binding protein subunit 1 (
). The CBC complex binds co-transcriptionally to the 5' cap of pre-mRNAs and is involved in maturation, export and degradation of nuclear mRNAs [
,
,
,
]. In humans, the CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus and plays a central role in nonsense-mediated mRNA decay (NMD) []. During cell proliferation, the CBC complex is involved in microRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2, thereby being required for miRNA-mediated RNA interference [].
This subfamily of pyridoxal phosphate-dependent enzymes includes known examples of both tyrosine aminotransferase from animals and nicotianamine aminotransferase from barley.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].Ribosomal protein S7 is one of the proteins from the small ribosomal subunit.
In Escherichia coli, S7 is known to bind directly to part of the 3'end of 16Sribosomal RNA. It belongs to a family of ribosomal proteins which have been grouped on the
basis of sequence similarities [
,
].This entry represents a conserved site located in the N-terminal section of the proteins.
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 [,
,
].
Lipoyl synthase is an iron-sulphur protein [
]. It is localised to mitochondria in yeast and Arabidopsis [,
]. It generates lipoic acid, a thiol antioxidant that is linked to a specific Lys as prosthetic group for the pyruvate and alpha-ketoglutarate dehydrogenase complexes and the glycine-cleavage system. This entry represents lipoyl synthase from plant mitochondria.
This region is found in a number of proteins identified as being involved in Golgi function and vacuolar sorting. The molecular function of this region is unknown. Proteins containing this domain also contain a C-terminal ring finger domain.
This domain is specific to the N-terminal part of the prp1 splicing factor, which is involved in mRNA splicing (and possibly also poly(A)+ RNA nuclear export and cell cycle progression). This domain is specific to the N terminus of the RNA splicing factor encoded by prp1 [
]. It is involved in mRNA splicing and possibly also poly(A)and RNA nuclear export and cell cycle progression.
This entry represents Pbs27, a small thylakoid lumen-localized protein known to serve as an assembly factor for the biogenesis and repair of the PSII complex [
]. Pbs27 is comprised of four helices arranged in a right handed up-down-up-down fold, with a less ordered region located at the N terminus [].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].The protein L2 is found in all ribosomes and is one of the best conserved proteins of this mega-dalton complex. L2 is elongated, exposing one end of the protein to the surface of the intersubunit interface of the 50 S subunit and is essential for the association of the ribosomal subunits and might participate in the binding and translocation of the tRNAs [
]. This entry represents bacterial, chloroplast and mitochondrial forms.
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 S8 is one of the proteins from the small ribosomal subunit. In Escherichia coli, S8 is known to bind
directly to 16S ribosomal RNA. It belongs to a family of ribosomal proteins which, on the basis of sequencesimilarities, groups eubacterial, algal and plant chloroplast, cyanelle, archaebacterial and
Marchantia polymorpha mitochondrial S8; mammalian and plant S15A; and yeast S22 (S24) ribosomal proteins.
This entry represents phytoene desaturase (PDS) from plants and cyanobacteria (blue-green algae). It is an essential carotenoid biosynthetic enzyme. It converts phytoene into zeta-carotene via the intermediary of phytofluene by the symmetrical introduction of two double bonds at the C-11 and C-11' positions of phytoene with a concomitant isomerization of two neighbouring double bonds at the C9 and C9' positions from trans to cis [
,
].This entry does not include plant chloroplast transit peptides and the entry does not contain zeta-carotene desaturase, which is a closely related family in the same pathway.
This entry represents the N-terminal domain of autophagy-related protein 13 (Atg13) from yeasts, animals and plants. They function in autophagy.Fission yeast autophagy initiation is controlled by the Atg1 kinase complex, which is composed of the Ser/Thr kinase Atg1, the adaptor protein Atg13, and the ternary complex of Atg17-Atg31-Atg29. Atg13 recruits Atg1 to the site of autophagosome formation and enhancing Atg1 kinase activity. Atg13 may have additional functions that are independent of a direct interaction or permanent colocalization with Atg1 [
]. In vertebrates, the orthologous ULK1 kinase complex contains the Ser/Thr kinase ULK1 and the accessory proteins ATG13, RB1CC1, and ATG101 [
]. Through its regulation of ULK1 activity, Atg13 plays a role in the regulation of the kinase activity of mTORC1 and cell proliferation [].
