A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.
A class of enzymes that catalyze the formation of a bond between two substrate molecules, coupled with the hydrolysis of a pyrophosphate bond in ATP or a similar energy donor. (Dorland, 28th ed) EC 6.
A highly conserved 76-amino acid peptide universally found in eukaryotic cells that functions as a marker for intracellular PROTEIN TRANSPORT and degradation. Ubiquitin becomes activated through a series of complicated steps and forms an isopeptide bond to lysine residues of specific proteins within the cell. These "ubiquitinated" proteins can be recognized and degraded by proteosomes or be transported to specific compartments within the cell.
A family of proteins that are structurally-related to Ubiquitin. Ubiquitins and ubiquitin-like proteins participate in diverse cellular functions, such as protein degradation and HEAT-SHOCK RESPONSE, by conjugation to other proteins.
A syndrome characterized by multiple abnormalities, MENTAL RETARDATION, and movement disorders. Present usually are skull and other abnormalities, frequent infantile spasms (SPASMS, INFANTILE); easily provoked and prolonged paroxysms of laughter (hence "happy"); jerky puppetlike movements (hence "puppet"); continuous tongue protrusion; motor retardation; ATAXIA; MUSCLE HYPOTONIA; and a peculiar facies. It is associated with maternal deletions of chromosome 15q11-13 and other genetic abnormalities. (From Am J Med Genet 1998 Dec 4;80(4):385-90; Hum Mol Genet 1999 Jan;8(1):129-35)
A class of enzymes that form a thioester bond to UBIQUITIN with the assistance of UBIQUITIN-ACTIVATING ENZYMES. They transfer ubiquitin to the LYSINE of a substrate protein with the assistance of UBIQUITIN-PROTEIN LIGASES.
A set of protein subcomplexes involved in PROTEIN SORTING of UBIQUITINATED PROTEINS into intraluminal vesicles of MULTIVESICULAR BODIES and in membrane scission during formation of intraluminal vesicles, during the final step of CYTOKINESIS, and during the budding of enveloped viruses. The ESCRT machinery is comprised of the protein products of Class E vacuolar protein sorting genes.
Complexes of enzymes that catalyze the covalent attachment of UBIQUITIN to other proteins by forming a peptide bond between the C-terminal GLYCINE of UBIQUITIN and the alpha-amino groups of LYSINE residues in the protein. The complexes play an important role in mediating the selective-degradation of short-lived and abnormal proteins. The complex of enzymes can be broken down into three components that involve activation of ubiquitin (UBIQUITIN-ACTIVATING ENZYMES), conjugation of ubiquitin to the ligase complex (UBIQUITIN-CONJUGATING ENZYMES), and ligation of ubiquitin to the substrate protein (UBIQUITIN-PROTEIN LIGASES).
The act of ligating UBIQUITINS to PROTEINS to form ubiquitin-protein ligase complexes to label proteins for transport to the PROTEASOME ENDOPEPTIDASE COMPLEX where proteolysis occurs.
A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.
An E3 ubiquitin ligase primarily involved in regulation of the metaphase-to-anaphase transition during MITOSIS through ubiquitination of specific CELL CYCLE PROTEINS. Enzyme activity is tightly regulated through subunits and cofactors, which modulate activation, inhibition, and substrate specificity. The anaphase-promoting complex, or APC-C, is also involved in tissue differentiation in the PLACENTA, CRYSTALLINE LENS, and SKELETAL MUSCLE, and in regulation of postmitotic NEURONAL PLASTICITY and excitability.
Enzymes that catalyze the joining of two molecules by the formation of a carbon-nitrogen bond. EC 6.3.
A subset of ubiquitin protein ligases that are formed by the association of a SKP DOMAIN PROTEIN, a CULLIN DOMAIN PROTEIN and a F-BOX DOMAIN PROTEIN.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Poly(deoxyribonucleotide):poly(deoxyribonucleotide)ligases. Enzymes that catalyze the joining of preformed deoxyribonucleotides in phosphodiester linkage during genetic processes during repair of a single-stranded break in duplex DNA. The class includes both EC 6.5.1.1 (ATP) and EC 6.5.1.2 (NAD).
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
An oligomer formed from the repetitive linking of the C-terminal glycine of one UBIQUITIN molecule via an isopeptide bond to a lysine residue on a second ubiquitin molecule. It is structurally distinct from UBIQUITIN C, which is a single protein containing a tandemly arrayed ubiquitin peptide sequence.
A class of enzymes that catalyzes the ATP-dependent formation of a thioester bond between itself and UBIQUITIN. It then transfers the activated ubiquitin to one of the UBIQUITIN-PROTEIN LIGASES.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
An enzyme that catalyzes the conversion of linear RNA to a circular form by the transfer of the 5'-phosphate to the 3'-hydroxyl terminus. It also catalyzes the covalent joining of two polyribonucleotides in phosphodiester linkage. EC 6.5.1.3.
A family of structurally related proteins that were originally discovered for their role in cell-cycle regulation in CAENORHABDITIS ELEGANS. They play important roles in regulation of the CELL CYCLE and as components of UBIQUITIN-PROTEIN LIGASES.
The form of fatty acid synthase complex found in BACTERIA; FUNGI; and PLANTS. Catalytic steps are like the animal form but the protein structure is different with dissociated enzymes encoded by separate genes. It is a target of some ANTI-INFECTIVE AGENTS which result in disruption of the CELL MEMBRANE and CELL WALL.
Incorporation of biotinyl groups into molecules.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
A thioester hydrolase which acts on esters formed between thiols such as DITHIOTHREITOL or GLUTATHIONE and the C-terminal glycine residue of UBIQUITIN.
A water-soluble, enzyme co-factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.
Catalyze the joining of preformed ribonucleotides or deoxyribonucleotides in phosphodiester linkage during genetic processes. EC 6.5.1.
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
A zinc-binding domain defined by the sequence Cysteine-X2-Cysteine-X(9-39)-Cysteine-X(l-3)-His-X(2-3)-Cysteine-X2-Cysteine -X(4-48)-Cysteine-X2-Cysteine, where X is any amino acid. The RING finger motif binds two atoms of zinc, with each zinc atom ligated tetrahedrally by either four cysteines or three cysteines and a histidine. The motif also forms into a unitary structure with a central cross-brace region and is found in many proteins that are involved in protein-protein interactions. The acronym RING stands for Really Interesting New Gene.
A family of proteins that share the F-BOX MOTIF and are involved in protein-protein interactions. They play an important role in process of protein ubiquition by associating with a variety of substrates and then associating into SCF UBIQUITIN LIGASE complexes. They are held in the ubiquitin-ligase complex via binding to SKP DOMAIN PROTEINS.
An octanoic acid bridged with two sulfurs so that it is sometimes also called a pentanoic acid in some naming schemes. It is biosynthesized by cleavage of LINOLEIC ACID and is a coenzyme of oxoglutarate dehydrogenase (KETOGLUTARATE DEHYDROGENASE COMPLEX). It is used in DIETARY SUPPLEMENTS.
Established cell cultures that have the potential to propagate indefinitely.
Ligases that catalyze the joining of adjacent AMINO ACIDS by the formation of carbon-nitrogen bonds between their carboxylic acid groups and amine groups.
ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
Systems of enzymes which function sequentially by catalyzing consecutive reactions linked by common metabolic intermediates. They may involve simply a transfer of water molecules or hydrogen atoms and may be associated with large supramolecular structures such as MITOCHONDRIA or RIBOSOMES.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
A carboxylating enzyme that catalyzes the conversion of ATP, acetyl-CoA, and HCO3- to ADP, orthophosphate, and malonyl-CoA. It is a biotinyl-protein that also catalyzes transcarboxylation. The plant enzyme also carboxylates propanoyl-CoA and butanoyl-CoA (From Enzyme Nomenclature, 1992) EC 6.4.1.2.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
A group of compounds with the general formula M10(PO4)6(OH)2, where M is barium, strontium, or calcium. The compounds are the principal mineral in phosphorite deposits, biological tissue, human bones, and teeth. They are also used as an anticaking agent and polymer catalysts. (Grant & Hackh's Chemical Dictionary, 5th ed)
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A conserved class of proteins that control APOPTOSIS in both VERTEBRATES and INVERTEBRATES. IAP proteins interact with and inhibit CASPASES, and they function as ANTI-APOPTOTIC PROTEINS. The protein class is defined by an approximately 80-amino acid motif called the baculoviral inhibitor of apoptosis repeat.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.
Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.
Transport proteins that carry specific substances in the blood or across cell membranes.
Enzymes that catalyze the formation of acyl-CoA derivatives. EC 6.2.1.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
A family of structurally-related proteins that were originally identified by their ability to complex with cyclin proteins (CYCLINS). They share a common domain that binds specifically to F-BOX MOTIFS. They take part in SKP CULLIN F-BOX PROTEIN LIGASES, where they can bind to a variety of F-BOX PROTEINS.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
Proto-oncogene proteins that negatively regulate RECEPTOR PROTEIN-TYROSINE KINASE signaling. It is a UBIQUITIN-PROTEIN LIGASE and the cellular homologue of ONCOGENE PROTEIN V-CBL.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
A single protein comprised of tandem repeats of the UBIQUITIN 78-amino acid sequence. It is a product of the polyubiquitin gene which contains multiple copies of the ubiquitin coding sequence. Proteolytic processing of ubiquitin C results in the formation of individual ubiquitin molecules. This protein is distinct from POLYUBIQUITIN, which is a protein formed through isopeptide linkage of multiple ubiquitin species.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A 1.5-kDa small ubiquitin-related modifier protein that can covalently bind via an isopeptide link to a number of cellular proteins. It may play a role in intracellular protein transport and a number of other cellular processes.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
Proteins found in any species of bacterium.
Proteins prepared by recombinant DNA technology.
Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.
A class of structurally related proteins of 12-20 kDa in size. They covalently modify specific proteins in a manner analogous to UBIQUITIN.
An essential amino acid. It is often added to animal feed.
A type of POST-TRANSLATIONAL PROTEIN MODIFICATION by SMALL UBIQUITIN-RELATED MODIFIER PROTEINS (also known as SUMO proteins).
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Proteins obtained from ESCHERICHIA COLI.
One of the enzymes active in the gamma-glutamyl cycle. It catalyzes the synthesis of gamma-glutamylcysteine from glutamate and cysteine in the presence of ATP with the formation of ADP and orthophosphate. EC 6.3.2.2.
Members of the peptidase C19 family which regulate signal transduction by removing UBIQUITIN from specific protein substrates via a process known as deubiquitination or deubiquitylation.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Proteins covalently modified with UBIQUITINS or UBIQUITIN-LIKE PROTEINS.
Macromolecular complexes formed from the association of defined protein subunits.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
A family of F-box domain proteins that contain sequences that are homologous to the beta subunit of transducin (BETA-TRANSDUCIN). They play an important role in the protein degradation pathway by becoming components of SKP CULLIN F-BOX PROTEIN LIGASES, which selectively act on a subset of proteins including beta-catenin and IkappaBbeta.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.
A family of structurally related proteins that are constitutively expressed and that negatively regulate cytokine-mediated SIGNAL TRANSDUCTION PATHWAYS. PIAS proteins inhibit the activity of signal transducers and activators of transcription.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.
The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.
An E3 UBIQUITIN LIGASE that interacts with and inhibits TUMOR SUPPRESSOR PROTEIN P53. Its ability to ubiquitinate p53 is regulated by TUMOR SUPPRESSOR PROTEIN P14ARF.
Cell surface receptors for AUTOCRINE MOTILITY FACTOR, which is the secreted form of GLUCOSE-6-PHOSPHATE ISOMERASE. The receptor has an unusual composition in that it shares some structural similarities with G-PROTEIN-COUPLED RECEPTORS and functions as an ubiquitin protein ligase when internalized.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
Compounds that inhibit the function or proteolytic action of the PROTEASOME.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A DNA amplification technique based upon the ligation of OLIGONUCLEOTIDE PROBES. The probes are designed to exactly match two adjacent sequences of a specific target DNA. The chain reaction is repeated in three steps in the presence of excess probe: (1) heat denaturation of double-stranded DNA, (2) annealing of probes to target DNA, and (3) joining of the probes by thermostable DNA ligase. After the reaction is repeated for 20-30 cycles the production of ligated probe is measured.
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.
Enzymes that catalyze the joining of two molecules by the formation of a carbon-oxygen bond. EC 6.1.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.
A group of acylated oligopeptides produced by Actinomycetes that function as protease inhibitors. They have been known to inhibit to varying degrees trypsin, plasmin, KALLIKREINS, papain and the cathepsins.
Protein modules with conserved ligand-binding surfaces which mediate specific interaction functions in SIGNAL TRANSDUCTION PATHWAYS and the specific BINDING SITES of their cognate protein LIGANDS.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.
Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.
Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation.
Proteins that originate from plants species belonging to the genus ARABIDOPSIS. The most intensely studied species of Arabidopsis, Arabidopsis thaliana, is commonly used in laboratory experiments.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A cell line derived from cultured tumor cells.
Joazeiro CA, Weissman AM (2000). "RING finger proteins: mediators of ubiquitin ligase activity". Cell. 102 (5): 549-52. doi: ... Many RING finger domains simultaneously bind ubiquitination enzymes and their substrates and hence function as ligases. ... This protein domain contains from 40 to 60 amino acids. Many proteins containing a RING finger play a key role in the ... They bind DNA, RNA, protein and/or lipid substrates. Their binding properties depend on the amino acid sequence of the finger ...
... is a mammalian gene encoding the protein CBL which is an E3 ubiquitin-protein ligase involved in cell signalling and protein ... Fang N, Fang D, Wang HY, Altman A, Liu YC (2002). "Regulation of immune responses by E3 ubiquitin-protein ligases". Curr. Dir. ... RING domain function in ubiquitin-protein ligases". Cell. 102 (4): 533-9. doi:10.1016/S0092-8674(00)00057-X. PMID 10966114. ... Cbl functions as an E3 ligase, and therefore is able to catalyse the formation of a covalent bond between ubiquitin and Cbl's ...
E3 ubiquitin-protein ligase NEDD4, also known as neural precursor cell expressed developmentally down-regulated protein 4 ( ... Harvey KF, Kumar S (1999). "Nedd4-like proteins: an emerging family of ubiquitin-protein ligases implicated in diverse cellular ... 3-4 WW protein-protein interaction domains, and a carboxyl-terminal catalytic HECT ubiquitin ligase domain. The C2 domain ... "Human ubiquitin-protein ligase Nedd4: expression, subcellular localization and selective interaction with ubiquitin-conjugating ...
Exhibits weak E3 ubiquitin-protein ligase activity. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating ... The human protein Mitochondrial E3 ubiquitin protein ligase 1 is ~40 kDa in size and composed of 352 amino acids. The ... Mitochondrial E3 ubiquitin protein ligase 1 (MUL1) is an enzyme that in humans is encoded by the MUL1 gene on chromosome 1. ... "Entrez Gene: MUL1 mitochondrial E3 ubiquitin protein ligase 1". Li W, Bengtson MH, Ulbrich A, Matsuda A, Reddy VA, Orth A, ...
E3 ubiquitin-protein ligase ZNRF1 is an enzyme that in humans is encoded by the ZNRF1 gene. In a study identifying genes in rat ... Araki T, Milbrandt J (2003). "ZNRF proteins constitute a family of presynaptic E3 ubiquitin ligases". J. Neurosci. 23 (28): ... indicating that it may be involved in ubiquitin-mediated protein modification. The protein encoded by this human gene is highly ... 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs ...
CBL-B is an E3 ubiquitin-protein ligase that in humans is encoded by the CBLB gene. CBLB is a member of the CBL gene family. ... 2002). "Regulation of immune responses by E3 ubiquitin-protein ligases". In Altman A (ed.). Signal Transduction Pathways in ... 2001). "Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-kinase for ubiquitination in T cells". J. Biol. ... 1997). "Cbl-b, a member of the Sli-1/c-Cbl protein family, inhibits Vav-mediated c-Jun N-terminal kinase activation". Oncogene ...
The protein encoded by this gene has ubiquitin-protein ligase activity. This protein binds with p53 and promotes the ubiquitin- ... "Differential response between the p53 ubiquitin-protein ligases Pirh2 and MdM2 following DNA damage in human cancer cells". ... "Cloning and characterization of an androgen receptor N-terminal-interacting protein with ubiquitin-protein ligase activity". ... "Cloning and characterization of an androgen receptor N-terminal-interacting protein with ubiquitin-protein ligase activity". ...
... ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin- ... Chuang TH, Ulevitch RJ (2004). "Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors". Nat. Immunol. 5 (5): ... Ubiquitin-conjugating enzyme E2 H is a protein that in humans is encoded by the UBE2H gene. The modification of proteins with ... "Downregulation of major histocompatibility complex class I by human ubiquitin ligases related to viral immune evasion proteins ...
This gene encodes a member of a subfamily of RING-finger type E3 ubiquitin ligases. The protein binds to hemi-methylated DNA ... "Critical role of the ubiquitin ligase activity of UHRF1, a nuclear RING finger protein, in tumor cell growth". Molecular ... "Np95 is a histone-binding protein endowed with ubiquitin ligase activity". Molecular and Cellular Biology. 24 (6): 2526-35. doi ... Ubiquitin-like, containing PHD and RING finger domains, 1, also known as UHRF1, is a protein which in humans is encoded by the ...
E3 ubiquitin-protein ligase UBR2 is an enzyme that in humans is encoded by the UBR2 gene. Proteolysis by the ubiquitin- ... The selectivity of ubiquitylation is determined by ubiquitin E3 ligases, which recognize the substrate's destabilization signal ... "Entrez Gene: UBR2 ubiquitin protein ligase E3 component n-recognin 2". CS1 maint: discouraged parameter (link) Nagase T, ... 2005). "Regulation of protein catabolism by muscle-specific and cytokine-inducible ubiquitin ligase E3alpha-II during cancer ...
... catenin and other cell-cycle regulatory proteins by targeting the F-box proteins of Skp1-Cul1-F-box protein E3 ubiquitin ligase ... 2005). "A Family of Mammalian E3 Ubiquitin Ligases That Contain the UBR Box Motif and Recognize N-Degrons". Mol. Cell. Biol. 25 ... "Entrez Gene: UBR1 ubiquitin protein ligase E3 component n-recognin 1". Varshavsky A (1996). "The N-end rule: functions, ... The human gene UBR1 encodes the enzyme ubiquitin-protein ligase E3 component n-recognin 1. The N-end rule pathway is one ...
identical protein binding. • ubiquitin protein ligase binding. • p53 binding. • SUMO transferase activity. • ubiquitin-protein ... Enzymes: Phosphoric ester and nitrogen-metal ligases (EC 6.5-6.6). 6.5: Phosphoric Ester. *DNA ligase ... protein N-terminus binding. • ubiquitin protein ligase activity. • NEDD8 ligase activity. • disordered domain specific binding ... Mouse double minute 2 homolog (MDM2) also known as E3 ubiquitin-protein ligase Mdm2 is a protein that in humans is encoded by ...
The E3 Ubiquitin ligase enzyme is a main component that provides specificity in protein degradation pathways, including immune ... Craig, A.; Ewan, R.; Mesmar, J.; Gudipati, V.; Sadanandom, A. (10 March 2009). "E3 ubiquitin ligases and plant innate immunity ... proteins with nucleotide-binding and leucine-rich repeat domains, also known as NLR proteins or STAND proteins, among other ... Although one of the main functions of ubiquitin is to target proteins for destruction, it is also useful in signaling pathways ...
... ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin- ... protein binding. • ATP binding. • ubiquitin conjugating enzyme activity. Cellular component. • cytosol. • ubiquitin ligase ... protein complex. • extracellular exosome. Biological process. • ubiquitin-dependent protein catabolic process. • protein ... "An altered-specificity ubiquitin-conjugating enzyme/ubiquitin-protein ligase pair". Journal of Molecular Biology. 337 (1): 157- ...
... more specifically ubiquitin protein ligases called E3, bind to the misfolded protein. Next they align the protein and E2, thus ... Parkin is a protein that functions in complex with CHIP as a ubiquitin ligase and overcomes the accumulation and aggregation of ... Most evidence suggest that the Hrd1 E3 ubiquitin-protein ligase can function as a retrotranslocon or dislocon to transport ... What is the channel for the retrotranslocation of luminal ER proteins?. *Which E3 ligase finally tags the proteins for the ...
ubiquitin protein ligase binding. • transcription regulatory region DNA binding. • ubiquitin-protein transferase activity. • ... The ring domain is an important element of ubiquitin E3 ligases, which catalyze protein ubiquitination. Ubiquitin is a small ... Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the BRCA1 (/ˌbrækəˈwʌn/) gene.[5] ... ubiquitin ligase complex. • plasma membrane. • nucleoplasm. • condensed chromosome. • cytoplasm. • chromosome. • cell nucleus. ...
Once a protein is tagged with a single ubiquitin molecule, this is a signal to other ligases to attach additional ubiquitin ... ubiquitin ligase by the APC/C(Cdh1) ubiquitin ligase". Nature. 428 (6979): 190-3. doi:10.1038/nature02330. PMID 15014502.. ... Ubiquitin-receptor proteins have an N-terminal ubiquitin-like (UBL) domain and one or more ubiquitin-associated (UBA) domains. ... The protein degradation processEdit. Ribbon diagram of ubiquitin, the highly conserved protein that serves as a molecular tag ...
protein binding. • metal ion binding. • ubiquitin protein ligase activity. • ubiquitin protein ligase binding. • ubiquitin- ... "Two Distinct Types of E3 Ligases Work in Unison to Regulate Substrate Ubiquitylation. ". Cell. 2016. PMID 27565346. ... Cul2-RING ubiquitin ligase complex. • Cul3-RING ubiquitin ligase complex. • Cul4A-RING E3 ubiquitin ligase complex. • Lewy body ... Protein sy'n cael ei godio yn y corff dynol gan y genyn ARIH1 yw ARIH1 a elwir hefyd yn Ariadne RBR E3 ubiquitin protein ligase ...
... to tether cellular proteins to a ubiquitin ligase, resulting in ubiquitination and degradation of the tethered protein.[23] ... protein exchange catalyst' that equilibrates F-box subunits of SCF ubiquitin ligases with the cullin scaffold subunit.[17] ... Mechanism of lysine 48-linked ubiquitin-chain synthesis by the cullin-RING ubiquitin-ligase complex SCF-Cdc34. Cell 123, 1107- ... SCF and cullin-RING ubiquitin ligases: As a postdoctoral fellow working with Dr. Marc Kirschner at the University of California ...
"Protein interaction analysis of SCF ubiquitin E3 ligase subunits from Arabidopsis". The Plant Journal. 34 (6): 753-67. doi: ... Once conjugated to ubiquitin, the E2 molecule binds one of several ubiquitin ligases or E3s via a structurally conserved ... a short protein of 76 amino acids, to a lysine residue on the target protein. Once a protein has been tagged with one ubiquitin ... Ubiquitin ligase. References[edit]. *^ Nandi D, Tahiliani P, Kumar A, Chandu D (2006). "The ubiquitin-proteasome system". ...
2000). "The inhibitor of apoptosis, cIAP2, functions as a ubiquitin-protein ligase and promotes in vitro monoubiquitination of ... "cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination". Mol. Cell ( ... Bakulovirusni protein 3 koji sadrži IAP ponavljanje (cIAP2) je protein koji je kod ljudi kodiran BIRC3 genom.[1][2] ... 2000). "Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins". ...
ubiquitin protein ligase binding. • peptidase activity. • cysteine-type endopeptidase activity involved in execution phase of ... "cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination". Mol. Cell. 30 ( ... protein complex binding. • scaffold protein binding. • protein binding. • identical protein binding. • cysteine-type ... The N-terminal FADD-like death effector domain of this protein suggests that it may interact with Fas-interacting protein FADD ...
protein binding. • cyclin-dependent protein serine/threonine kinase inhibitor activity. • ubiquitin protein ligase binding. • ... p21 is negatively regulated by ubiquitin ligases both over the course of the cell cycle and in response to DNA damage. ... cyclin-dependent protein serine/threonine kinase activity. • protein kinase inhibitor activity. • protein kinase binding. • ... This article is about the p21Cip1 protein. For the p21/ras protein, see Ras (protein). For other uses, see P21 (disambiguation) ...
Enzymes: Phosphoric ester and nitrogen-metal ligases (EC 6.5-6.6). 6.5: Phosphoric Ester. *DNA ligase ... McClain WH (November 1993). "Rules that govern tRNA identity in protein synthesis". Journal of Molecular Biology. 234 (2): 257- ... Long-chain-fatty-acid-CoA ligase. 6.3: Carbon-Nitrogen. *Glutamine synthetase. *Ubiquitin ligase *Cullin ... An aminoacyl-tRNA synthetase (aaRS or ARS), also called tRNA-ligase, is an enzyme that attaches the appropriate amino acid onto ...
Stage two involves four key Mur ubiquitin ligase enzymes: MurC (EC),[1] MurD (EC),[2] MurE (EC) [3] and MurF (EC).[4] These ... All four Mur ligases are topologically similar to one another, even though they display low sequence identity. They are each ... "Protein Sci. 14 (12): 3039-47. doi:10.1110/ps.051604805. PMC 2253247. PMID 16322581.. ... 6-diaminopimelate ligase (MurE), and UDP-N-acetylmuramoyl-tripeptide-D-alanyl-D-alanine ligase (MurF). This entry also includes ...
... ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E1 ubiquitin- ... ligase activity. • protein binding. • protein heterodimerization activity. • acid-amino acid ligase activity. • NEDD8 ... The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins ... ubiquitin-like modifier activating enzyme activity. • ATP binding. • identical protein binding. • NEDD8 transferase activity. • ...
... ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin- ... ubiquitin conjugating enzyme activity. • ubiquitin-protein transferase activity. • transferase activity. • protein binding. ... The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins ... protein K48-linked ubiquitination. • protein K11-linked ubiquitination. • regulation of growth. • protein ubiquitination. ...
RCSB Protein Data Bank. Retrieved 2010-05-08.. *^ a b c d e Krajewski WW, Collins R, Holmberg-Schiavone L, Jones TA, Karlberg T ... Long-chain-fatty-acid-CoA ligase. 6.3: Carbon-Nitrogen. *Glutamine synthetase. *Ubiquitin ligase *Cullin ... Enzymes: CO CS and CN ligases (EC 6.1-6.3). 6.1: Carbon-Oxygen. *Aminoacyl tRNA synthetase *Alanine ... "Glutamine synthetase inactivation by protein-protein interaction". Proceedings of the National Academy of Sciences of the ...
protein kinase activity. • kinase activity. • protein binding. • protein tyrosine kinase activity. • ATP binding. • Ras guanyl- ... membrane protein proteolysis. • phosphorylation. • transmembrane receptor protein tyrosine kinase signaling pathway. • positive ... Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7). *Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ... "The Ret receptor protein tyrosine kinase associates with the SH2-containing adapter protein Grb10". J. Biol. Chem. 270 (37): ...
Long-chain-fatty-acid-CoA ligase. 6.3: Carbon-Nitrogen. *Glutamine synthetase. *Ubiquitin ligase *Cullin ... The small subunit has a 3-layer beta/beta/alpha structure, and is thought to be mobile in most proteins that carry it. The C- ... Enzymes: CO CS and CN ligases (EC 6.1-6.3). 6.1: Carbon-Oxygen. *Aminoacyl tRNA synthetase *Alanine ... DNA sequence and evolution of the CPS domain of the Syrian hamster multifunctional protein CAD". J. Biol. Chem. 265 (18): 10395 ...
2003). "Interaction between two ubiquitin-protein isopeptide ligases of different classes, CBLC and AIP4/ITCH". J. Biol. Chem. ... Kassenbrock CK, Anderson SM (2004). "Regulation of ubiquitin protein ligase activity in c-Cbl by phosphorylation-induced ... Signal transduction protein CBL-C is a protein that in humans is encoded by the CBLC gene. CBL proteins, such as CBLC, are ... Through interactions with proteins containing SRC (MIM 190090) homology-2 (SH2) and SH3 domains, CBL proteins modulate ...
"RNF144A - E3 ubiquitin-protein ligase RNF144A - Homo sapiens (Human) - RNF144A gene & protein". www.uniprot.org. UniProt. ... RNF144A is an E3 ubiquitin ligase belonging to the RING-between RING (RBR) family of ubiquitin ligases, whose specific members ... The ubiquitin ligase activity of RNF144A catalyzes ubiquitin linkages at the K6-, K11- and K48- positions of ubiquitin in vitro ... Zhang Y, Liao XH, Xie HY, Shao ZM, Li DQ (November 2017). "RBR-type E3 ubiquitin ligase RNF144A targets PARP1 for ubiquitin- ...
E3 ubiquitin-protein ligase TRIM63, also known as "MuRF1" is an enzyme that in humans is encoded by the TRIM63 gene. This gene ... 2001). "Identification of ubiquitin ligases required for skeletal muscle atrophy". Science. 294 (5547): 1704-8. Bibcode:2001Sci ... Trim63/MuRF1 has been shown to be an E3 ubiquitin ligase. Its major substrate is Myosin Heavy Chain. MuRF1 is upregulated ... 2005). "Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I." Proc. Natl. Acad. Sci ...
Ubiquitin ligases target proteins for degradation through ubiquitin modification. Protein aggregation can be caused by problems ... The E3 ubiquitin ligase is able to recognize misfolded proteins and ubiquinate them. HDAC6 can then bind to the ubiquitin and ... ubiquitin ligases). Chaperones help with protein refolding by providing a safe environment for the protein to fold. ... In yeast, the E3 ligases Doa10 and Hrd1 have similar functions on endoplasmic reticulum proteins. Misfolded proteins can also ...
"Certain pairs of ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s) synthesize nondegradable forked ... The E6 proteins of HPV will bind to the N-terminus of the cellular E6-AP E3 ubiquitin ligase, redirecting the complex to bind ... Few ubiquitin-like protein (FUB1), MUB (membrane-anchored UBL), ubiquitin fold-modifier-1 (UFM1) and ubiquitin-like protein-5 ( ... The protein modifications can be either a single ubiquitin protein (monoubiquitylation) or a chain of ubiquitin ( ...
... of multiple proteins expressed in murine embryos as binding partners for the WW domains of the ubiquitin-protein ligase Nedd4 ... Burger A, Amemiya Y, Kitching R, Seth AK (2006). "Novel RING E3 ubiquitin ligases in breast cancer". Neoplasia. 8 (8): 689-95. ... RING finger protein 11 is a protein that in humans is encoded by the RNF11 gene. The protein encoded by this gene contains a ... "Entrez Gene: RNF11 ring finger protein 11". Shembade N, Parvatiyar K, Harhaj NS, Harhaj EW (March 2009). "The ubiquitin-editing ...
... is a ubiquitin-protein ligase (E3) that accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a ... Harvey KF, Kumar S (May 1999). "Nedd4-like proteins: an emerging family of ubiquitin-protein ligases implicated in diverse ... ubiquitin ligase) of the NEDD4 family. In human the protein is encoded by the NEDD4L gene. In mouse the protein is commonly ... protein-protein interaction domains) and the carboxyl-terminal HECT domain (ubiquitin ligase domain). The WW domains in the ...
... is a multi-protein E3 ubiquitin ligase complex that catalyzes the ubiquitination of proteins destined for 26S proteasomal ... post-translational modifications of regulatory proteins. Of these regulatory proteins, two ubiquitin ligases are crucial for ... This binding event allows the transferral of ubiquitin from E2 to a lysine residue on the target protein. The first hint that ... Different combinations of Cullin and FBPs can generate on the order of a hundred types of E3 ubiquitin ligases that target ...
... thus defining a novel family of ZNRF E3 ubiquitin ligases. Both ZNRF1 and ZNRF2 have E3 ubiquitin ligase activity and are ... ZNRF proteins are E3 ubiquitin ligases. Many proteins containing RING finger(s) function as E3 ubiquitin ligases; we therefore ... Hatakeyama S, Yada M, Matsumoto M, Ishida N, Nakayama KI (2001) U box proteins as a new family of ubiquitin-protein ligases. J ... we defined a novel family of E3 ubiquitin ligases, the ZNRF proteins, through the identification of ZNRF2, a protein homologous ...
The G protein β subunit functions as an adaptor subunit for an E3 ligase that ubiquitylates the G protein-coupled receptor ... Gβ proteins as components of E3 ubiquitin ligases Message Subject. (Your Name) has forwarded a page to you from Science ... The G protein β subunit functions as an adaptor subunit for an E3 ligase that ubiquitylates the G protein-coupled receptor ...
The role of ubiquitin-protein ligases in neurodegenerative disease. Neurodegener Dis. 2004;1(2-3):71-87. PMID:16908979 doi:http ... Herbicide 2,4-D bound to TIR1 Ubiquitin Ligase. 3D Structures of ubiquitin protein ligase. Ubiquitin protein ligase 3D ... Ubiquitin-protein ligase (UPL) (E3) or E3 ubiquitin-protein ligase in combination with ubiquitin-conjugating enzyme (E2) causes ... For E3 ubiquitin-protein ligase parkin see Parkin. Disease XIAP mutations cause X-linked lymphoproliferative syndrome type 2[3] ...
E2 ubiquitin-conjugating enzymes, and E3 ubiquitin ligases. Among these, E3 ubiquitin ligases play a crucial role in defining ... The domain structure of the predicted Drosophila Smurf1 protein is typical for HECT domain ubiquitin-protein ligases, and ... Classification - ubiquitin-protein ligase Cellular location - cytoplasmic NCBI links: Entrez Gene. Smurf orthologs: Biolitmine ... Gene name - SMAD specific E3 ubiquitin protein ligase Synonyms - Smurf Cytological map position - 54C--D Function - enzyme ...
Because proteins with a RING domain usually function as E3 ubiquitin ligases (18⇓-20), we tested whether SOR1 also possesses E3 ... E3 ubiquitin ligase SOR1 regulates ethylene response in rice root by modulating stability of Aux/IAA protein. Hui Chen, Biao Ma ... E3 ubiquitin ligase-mediated protein degradation plays a central role in ethylene and auxin signaling. The stability of ... D) GST-SOR1T protein (∼45 kDa) displays E3 ubiquitin ligase activity in vitro. GST itself was used as a negative control. ...
... availability are also targeted for proteosome-dependent degradation by the E3 ubiquitin ligases Siah1a and Siah2 [3]. ... Synonyms: E3 ubiquitin-protein ligase SIAH1, HUMSIAH, Seven in absentia homolog 1, Siah-1, Siah-1a, ... ... Taken together, the data imply that the Sina/Siah proteins regulate DCC and perhaps other proteins via the ubiquitin-proteasome ... we describe the identification of an E3 ubiquitin ligase, Seven in Absentia homologue-1 (SIAH1), as a TIEG1-interacting protein ...
... and a ubiquitin ligase (E3). The specificity in protein ubiquitination often derives from the E3 ubiquitin ligases. Proteins ... Ubiquitin-dependent degradation of IκBα is mediated by a ubiquitin ligase Skp1/Cul 1/F-box protein FWD1. Shigetsugu Hatakeyama ... Ubiquitin-dependent degradation of IκBα is mediated by a ubiquitin ligase Skp1/Cul 1/F-box protein FWD1 ... Ubiquitin-dependent degradation of IκBα is mediated by a ubiquitin ligase Skp1/Cul 1/F-box protein FWD1 ...
Ubiquitin-Protein Ligases * Ubiquitins / metabolism Substances * Arid4a protein, mouse * Carrier Proteins * Cell Cycle Proteins ... which is the cell-cycle-regulated component of the ubiquitin-protein ligase SCFSKP2 that recognizes substrates for this ligase ... Interaction between ubiquitin-protein ligase SCFSKP2 and E2F-1 underlies the regulation of E2F-1 degradation Nat Cell Biol. ... This event is linked to a specific interaction of E2F-1 with the F-box-containing protein p45SKP2, ...
The degradation of specific target proteins is mediated by ubiquitin-protein ligases (E3), which mark their target proteins ... Fbx15 can be incorporated into SCF E3 ubiquitin ligases and controls upon stress the nuclear localization of the SsnF. Fbx15 ... with ubiquitin for proteasomal degradation. Multisubunit SCF Cullin1 Ring ligases (CRL) are E3 ligases where the F-box subunit ... We have identified a novel connection between protein degradation and synthesis through an F-box protein. ...
... which encodes ubiquitin-protein ligase, and mdp1 mutations are suppressed by high copy expression of ubiquitin. All four ... mutations cause missense changes located in the hect domain of Rsp5p that is highly conserved among ubiquitin-protein ligases. ... Is Identical to the Ubiquitin-Protein Ligase Gene RSP5 Teresa Żołądek, Anna Tobiasz, Gabriela Vaduva, Magda Boguta, Nancy C. ... Is Identical to the Ubiquitin-Protein Ligase Gene RSP5 Teresa Żołądek, Anna Tobiasz, Gabriela Vaduva, Magda Boguta, Nancy C. ...
... cells with β-elemene led to downregulation of Akt phosphorylation and significant upregulation of the E3 ubiquitin ligases, c- ... Keywords: E3 ubiquitin ligase; β-elemene; multidrug resistance; PI3K/Akt E3 ubiquitin ligase; β-elemene; multidrug resistance; ... Zhang Y, Mu X-D, Li E-Z, Luo Y, Song N, Qu X-J, Hu X-J, Liu Y-P. The Role of E3 Ubiquitin Ligase Cbl Proteins in β-Elemene ... The Role of E3 Ubiquitin Ligase Cbl Proteins in β-Elemene Reversing Multi-Drug Resistance of Human Gastric Adenocarcinoma Cells ...
Kume K, Iizumi Y, Shimada M, Ito Y, Kishi T, Yamaguchi Y, Handa H: Role of N-end rule ubiquitin ligases UBR1 and UBR2 in ... Showing Protein E3 ubiquitin-protein ligase UBR2 (HMDBP09274). IdentificationBiological propertiesGene propertiesProtein ... Involved in protein catabolic process. Specific Function. E3 ubiquitin-protein ligase which is a component of the N-end rule ... Protein Sequence. ,E3 ubiquitin-protein ligase UBR2 MASELEPEVQAIDRSLLECSAEEIAGKWLQATDLTREVYQHLAHYVPKIYCRGPNPFPQK ...
The APC/C E3 Ligase Complex Activator FZR1 Restricts BRAF Oncogenic Function.  Wan, Lixin; Chen, Ming; Cao, Juxiang; Dai, ... Browsing Duke Scholarly Works by Subject "Ubiquitin-Protein Ligases". 0-9. A. B. C. D. E. F. G. H. I. J. K. L. M. N. O. P. Q. R ... They are inhibited by ubiquitin protein ligases, such as Nedd4 and Nedd4-2, ... ... A network of substrates of the E3 ubiquitin ligases MDM2 and HUWE1 control apoptosis independently of p53.  Kurokawa, Manabu; ...
... possible natural substrates of these ubiquitin ligases).. We tested 10 different vacuolar membrane proteins that have been ... A transmembrane ubiquitin ligase required to sort membrane proteins into multivesicular bodies. Nat. Cell Biol. 4:117-123. doi: ... Distinct ubiquitin-ligase complexes define convergent pathways for the degradation of ER proteins. Cell. 126:361-373. doi: ... Retrotranslocation of a misfolded luminal ER protein by the ubiquitin-ligase Hrd1p. Cell. 143:579-591. doi:10.1016/j.cell. ...
A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. Proc. Natl. Acad. Sci. USA. ... Proteins related to the Nedd4 family of ubiquitin protein ligases intereact with the L domain of Rous sarcoma virus and are ... Ubiquitination and endocytosis of plasma membrane proteins: role of Nedd4/Rsp5p family of ubiquitin-protein ligases. J. Membr. ... Recruitment of HECT ubiquitin ligases to VPS4-induced endosomes. These data demonstrate that certain HECT ubiquitin ligases can ...
Ubiquitin-Protein Ligases 75% * Protective Factors 70% * Type 2 Diabetes Mellitus 49% ... Intra-islet inflammation in type 2 diabetes: evidence that the E3 ligase TRAF2 is a key protective factor in beta cells. Malle ...
... the natural function of E3 ligases within the ubiquitin proteasome system to selectively decrease or increase cellular protein ... a B-cell signaling protein, and inhibitors of Casitas B-lineage lymphoma proto-oncogene-B, an E3 ligase that regulates T cell ... Leveraging Nurixs extensive expertise in E3 ligases together with its proprietary DNA-encoded libraries, Nurix has built ... Nurixs wholly owned pipeline comprises targeted protein degraders of Brutons tyrosine kinase, ...
Ubiquitin-Protein Ligases Medicine & Life Sciences 74% * Xenobiotics Medicine & Life Sciences 71% ... the NRF2 pathway is activated by inhibition of the E3 ubiquitin ligase complex that normally marks NRF2 for destruction. For ... the NRF2 pathway is activated by inhibition of the E3 ubiquitin ligase complex that normally marks NRF2 for destruction. For ... the NRF2 pathway is activated by inhibition of the E3 ubiquitin ligase complex that normally marks NRF2 for destruction. For ...
The EGFR mutants were constitutively associated with the E3 ubiquitin ligase Cbl but did not associate with the adaptor protein ... Ubiquitin-Protein Ligases Medicine & Life Sciences 14% * Ubiquitination Medicine & Life Sciences 14% ... The EGFR mutants were constitutively associated with the E3 ubiquitin ligase Cbl but did not associate with the adaptor protein ... The EGFR mutants were constitutively associated with the E3 ubiquitin ligase Cbl but did not associate with the adaptor protein ...
It shows genes and PPIs with information about pathways, protein-protein interactions (PPIs), Gene Ontology (GO) annotations ... a web resource for human protein-protein interactions. ... WW domain containing E3 ubiquitin protein ligase 2. ubiquitin- ... anticancer biomarker cascade catalyzes contributes counterparts deleted dramatic e3 encodes final homologue ligase ligases ... Protein Ubiquitination Involved In Ubiquitin-dependent Protein Catabolic Process. *Proteasome-mediated Ubiquitin-dependent ...
It shows genes and PPIs with information about pathways, protein-protein interactions (PPIs), Gene Ontology (GO) annotations ... a web resource for human protein-protein interactions. ... WW domain containing E3 ubiquitin protein ligase 2. ubiquitin- ... anticancer biomarker cascade catalyzes contributes counterparts deleted dramatic e3 encodes final homologue ligase ligases ... Protein Ubiquitination Involved In Ubiquitin-dependent Protein Catabolic Process. *Proteasome-mediated Ubiquitin-dependent ...
De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome.. Matsuura T, Sutcliffe JS, ... Structure of an E3:E2~Ub complex reveals an allosteric mechanism shared among RING/U-box ligases.. Pruneda JN, Littlefield PJ, ... Basis for a ubiquitin-like protein thioester switch toggling E1-E2 affinity.. Huang DT, Hunt HW, Zhuang M, Ohi MD, Holton JM, ... How the ubiquitin-proteasome system controls transcription.. Muratani M, Tansey WP. (2003) Nat Rev Mol Cell Biol 4: 192-201 ...
bid deficiency resulted in increased A20-E3 ubiquitin ligase protein interactions in glia, specifically A20-TRAF6 and A20-TRAF3 ... Interactions between the de-ubiquitinating Smad6-A20 and the E3 ubiquitin ligases, TRAF3 and TRAF6, were determined by FLAG ... Increased A20-E3 ubiquitin ligase interactions in bid-deficient g. .pdf (. 2.03 MB. ) ... Increased A20-E3 ubiquitin ligase interactions in bid-deficient glia attenuateTLR3- and TLR4-induced inflammation. Kinsella et ...
PARK2 is broadly expressed in a variety of cells and encodes an E3 ubiquitin ligase for proteosome-mediated proteins ... This intronless gene encodes a 70kDa heat shock protein which is a member of the heat shockprotein 70 family. In conjuction ... Furthermore, we noticed the visible adjustments in manifestation from the VEGF, p-JAK2, and p-STAT3 protein using interleukin-6 ... deletion or mutation directly eliminates or reduces PARK2 protein production in cells, respectively, and improves tumor growth ...
UBE2R1 also catalyzes polyubiquitylation of a substrate recruited by the Skp1-Cullin 1-F-box protein-ROC1 E3 ubiquitin ligase. ... and protein ligases (E3s). UBE2R1 is a member of the E2 conjugating enzyme family and cloning of the human gene was first ... E2-Ubiquitin Thioester Loading Assay: The activity of His-UBE2R1 was validated by loading E1 UBE1 activated ubiquitin onto the ... Incubation of the UBE1 and His-UBE2R1 enzymes in the presence of ubiquitin and ATP at 30oC was compared at two time points, T0 ...
... complexing the stem cell markers LGR4-6 with the Frizzled-specific E3 ubiquitin ligases ZNRF3/RNF43. The consequent ... Rspo proteins act by cross-linking members of two cell surface receptor families, ... internalisation of the ternary LGR-Rspo-E3 complex removes the E3 ligase activity, which otherwise targets the Wnt receptor ... This crystal structure confirms our previously suggested hypothesis, showing that Rspo proteins cross-link LGRs and ZNRF3 into ...
CRL E3 ubiquitin ligases [cytosol] (Schizosaccharomyces pombe) * SCF E3 ubiquitin ligase [cytosol] (Schizosaccharomyces pombe) ... SCF E3 ubiquitin ligase [cytosol] (Schizosaccharomyces pombe) * F-box protein [cytosol] (Schizosaccharomyces pombe) * ... CRL E3 ubiquitin ligases [cytosol] (Schizosaccharomyces pombe) * SCF E3 ubiquitin ligase [cytosol] (Schizosaccharomyces pombe) ... CAND1 binds cytosolic CRL E3 ubiquitin ligases (Schizosaccharomyces pombe) * CRL E3 ubiquitin ligase:CAND1 [cytosol] ( ...
A serine the first transmembrane domain of the human E3 ubiquitin ligase MARCH9 is critical for down-regulation of its protein ... E3 ubiquitin ligases in neurodegeneration, autoinflammation and cancer. *Engineering improved CAR-T cell therapies ...
PROTACs are small heterobifunctional molecules based on the combination of ubiquitin E3 ligase ligands with the protein of ... The human genome encodes more than 600 E3 ligases, and the ligands to E3 proteins should at least be equal to E3 ligases in ... E3 Ligase and Target Proteins. Rather than directly occupying an active site to modify protein function, PROTAC takes advantage ... Creative Biolabs provides different products of E3 ligase proteins and target proteins to better optimization and ...
... a subunit of E3 Skp1/Cullin-1/F-box protein ubiquitin ligases, is modified by a prolyl hydroxylase that mediates O2-regulation ... A terminal α3-galactose modification regulates an E3 ubiquitin ligase subunit in Toxoplasma gondii. Posted on May 15, 2020 in ... The nucleocytosolic O-fucosyltransferase Spindly affects protein expression and virulence in Toxoplasma gondii. Posted on Nov 9 ... While in animals O-GlcNAc transferase (OGT) modifies thousands of intracellular proteins, the human pathogen Toxoplasma gondii ...
identify a novel signaling link between the major ubiquitin ligase Cdh1-APC and the fragile X syndrome protein FMRP that ... identify a novel signaling link between the major ubiquitin ligase Cdh1-APC and the fragile X syndrome protein FMRP that ... identify a novel signaling link between the major ubiquitin ligase Cdh1-APC and the fragile X syndrome protein FMRP that ... identify a novel signaling link between the major ubiquitin ligase Cdh1-APC and the fragile X syndrome protein FMRP that ...
... which is composed of the two E3 ubiquitin ligases HOIP and HOIL-1L and the adaptor protein SHARPIN. Upon TNF stimulation, PACRG ... which encodes an E3 ubiquitin ligase. Because PRKN is important in mitochondrial quality control and protection against stress ... The Parkin-coregulated gene (PACRG), which encodes a protein of unknown function, shares a bidirectional promoter with Parkin ( ... activation in the absence of PACRG was accompanied by a decrease in linear ubiquitylation mediated by the linear ubiquitin ...
The Hsp70-interacting E3-ubiquitin ligase CHIP has been implicated in the decision as to whether a target protein enters the ... The Hsp70-interacting E3-ubiquitin ligase CHIP has been implicated in the decision as to whether a target protein enters the ... In contrast to other E3-ubiquitin ligases, both h...更多 ... Dimerization of the human E3 ligase CHIP via a coiled-coil ...
It shows genes and PPIs with information about pathways, protein-protein interactions (PPIs), Gene Ontology (GO) annotations ... a web resource for human protein-protein interactions. ... Regulation Of Ubiquitin-protein Ligase Activity Involved In ... coordinates cytosol ddr enables exit flanking genotoxic h2a homologous impairs interphase joining kinetochores ligases localize ... Positive Regulation Of Ubiquitin-protein Ligase Activity Involved In Regulation Of Mitotic Cell Cycle Transition ...
Our drugs control ubiquitin E3 ligases, the key enzymes responsible for protein breakdown in human cells, as a unique ... Leveraging Nurixs extensive expertise in E3 ligases together with its proprietary DNA-encoded libraries, Nurix has built ... Nurix Therapeutics discovers drugs that harness the bodys natural process to control protein levels. ... and commercialization of small molecule therapies designed to modulate cellular protein levels as a novel treatment approach ...
Additional studies indicated that the regulation of ubiquitin ligase activity of TRAF6 and RIP1 by CYLD was related to the ... miR-194 could promote muscle differentiation and also inhibit ubiquitin ligases, thus miR-194 could be used as a nucleic acid ... The protein levels of hub genes were verified in HPA. The interaction between the hub genes and the drug were identified in ... The mRNA levels and protein levels of CDK1, HMMR, PTTG1, and TTK were higher in liver cancer tissues compared to normal tissues ...
... ubiquitin ligases are mutated or lost in a high proportion of human tumours and exert their function by regulating the protein ... Chakraborty, A., Diefenbacher, M.E., Mylona, A., Kassel, O., and Behrens, A. (2015). The E3 ubiquitin ligase Trim7 mediates c- ... Markus Diefenbacher: E3-ligases and Deubiquitinases in cancer Summary. Our research focus is the deregulation of protein ... try to understand the consequences of loss/mutation of key-components of the ubiquitin machinery and ways to counteract protein ...
... which enhances the ubiquitin ligase activity of Mdm2 for p53. This technique favours the change and proliferation of EBV- ... DNA Ligases *DNA-Dependent Protein Kinase *Dopamine D1 Receptors *Dual-Specificity Phosphatase ... Here, we record that HIV-1 Tat elevated Mdm2 protein amounts by stabilising it, making a positive feedback loop between Tat and ... most famous protein\producing organs in scientific literature. Supplementary MaterialsSupplementary Information. (Quantikine ...
DNA Ligase *DNA Ligases *DNA Methyltransferases *DNA Topoisomerase *DNA, RNA and Protein Synthesis ... deltex-3-like E3 ubiquitin ligase (DTX3L) (also called Mometasone furoate BBAP) NF-kappaB inducing kinase (NIK) and changing ... Many book potential drug goals have been lately discovered like the Wager bromodomain proteins (BRD)-4 Mometasone furoate ...
Ubiquitin E3 Ligases *Ubiquitin/Proteasome System *Uncategorized *Urotensin-II Receptor *Vesicular Monoamine Transporters ... such as for example DNA DNA and polymerase ligase III. PARP also induces apoptosis through elevated poly (ADP-ribose) (PAR) ... and denaturation of proteins [3]. Oxidative modification to DNA structure mainly occurs in the form of base oxidation. Guanine ...
... the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43), ... these secreted proteins require leucine-rich repeat-containing G-protein coupled receptor (LGR) 4 and 5 to be active [20,21]. R ... which increases the membrane level of Wnt receptors [22,23]. ZNRF3 and RNF43 are single-pass transmembrane E3 ligases ... They are a family of secreted proteins that prevent LRP5/6 internalization and increase the activation of the Wnt/-catenin ...
... resulting from an enzymatic ubiquitin cascade without the need of running and staining ... Parkin TR-FRET Ubiquitin Kit South Bay Bios MDM2 TR-FRET Ubiquitin Kit provides a fast and sensitive method monitoring ... Protein Production. All our proteins are produced on-site by a team of dedicated scientists with decades of protein ... Parkin E3 Ligase TR-FRET Kit Catalog number: SBB-KF0036, 400 wells. The kit uses ubiquitin labeled with either Europium- ...
It shows genes and PPIs with information about pathways, protein-protein interactions (PPIs), Gene Ontology (GO) annotations ... a web resource for human protein-protein interactions. ... Regulation Of Ubiquitin-protein Ligase Activity Involved In ... coordinates cytosol ddr enables exit flanking genotoxic h2a homologous impairs interphase joining kinetochores ligases localize ... Positive Regulation Of Ubiquitin-protein Ligase Activity Involved In Regulation Of Mitotic Cell Cycle Transition ...
  • Here, we review the substrates and pathways regulated by the yeast F-box proteins Cdc4, Grr1 and Met30. (nih.gov)
  • E3 proteins recruit substrates to the ubiquitination machinery and play a crucial role in specifying which proteins are selected for ubiquitination. (jneurosci.org)
  • This event is linked to a specific interaction of E2F-1 with the F-box-containing protein p45SKP2, which is the cell-cycle-regulated component of the ubiquitin-protein ligase SCFSKP2 that recognizes substrates for this ligase. (nih.gov)
  • A network of substrates of the E3 ubiquitin ligases MDM2 and HUWE1 control apoptosis independently of p53. (duke.edu)
  • Prototypic CRLs, "SCFs", comprise the scaffold protein CUL1, the RING protein RBX1, the adaptor SKP1, and an F-box protein that both binds SKP1 and recruits substrates for RBX1-mediated ubiquitination 1 , 5 , 6 . (pubmedcentralcanada.ca)
  • We have also detected other substrates for ICP0-induced degradation, including the catalytic subunit of DNA protein kinase ( 35 ) and the centromere proteins CENP-C ( 7 ) and CENP-A ( 27 ). (asm.org)
  • The multisubunit Cullin-RING Ligases ( CRLs ) are a highly polymorphic collection of E3s composed of a Cullin (CUL) backbone subunit onto which assembles the E2- Ub -docking RING Box1 (RBX1) protein and a diverse assortment of adaptors that recruit ubiquitylation substrates ( Hua and Vierstra, 2011 ). (plantphysiol.org)
  • Creating inhibitors that will block the in vivo activities of specific SCF ubiquitin ligases may provide identification of substrates of these uncharacterized F-box proteins. (asm.org)
  • HECT domain E3 ubiquitin ligases transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein substrates, thus targeting specific proteins for lysosomal degradation. (cancer.gov)
  • The hairpin‐containing lipid droplet ( LD ) proteins Pgc1, Dga1, and Yeh1 are substrates of the ERAD ubiquitin ligase Doa10. (embopress.org)
  • We have now devised a protocol to screen for substrates of this particular ubiquitin ligase . (symptoma.com)
  • A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. (rush.edu)
  • An E2-ubiquitin thioester-driven approach to identify substrates modified with ubiquitin and ubiquitin-like molecules. (icr.ac.uk)
  • E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. (uniprot.org)
  • These complexes are targeted to specific substrates via interchangeable substrate recognition subunits, including F-box proteins for SCF and cell division cycle 20 (CDC20) and CDH1 for APC/C. These multisubunit E3s have a large number of substrates with oncogenic and tumour suppressive effects. (nature.com)
  • The requirement for substrate modification prior to ubiquitylation allows the same ligase to target different substrates within the same cell at different times. (eurekaselect.com)
  • The cullin-RING ubiquitin ligases (CRLs) are the largest E3 ligase family in eukaryotes, and ubiquitinate a wide array of substrates involved in cell cycle, signaling, DNA damage response, gene expression, chromatin remodeling, and embryonic development. (frontiersin.org)
  • Within the E2-E3 complex, the RING domain-containing Rbx1/ROC1/Hrt1 or Rbx2/SAG adaptor bridges E2 binding to the cullin carboxyl terminus, which is necessary for transfer of ubiquitin to all cullin substrates. (frontiersin.org)
  • The prototype U box protein, yeast Ufd2, was identified as a ubiquitin chain assembly factor that cooperates with a ubiquitin-activating enzyme (El), a ubiquitin-conjugating enzyme (E2), and a ubiquitin-protein ligase (E3) to catalyze ubiquitin chain formation on artificial substrates. (elsevier.com)
  • Cul1 associates with one of many F-box proteins through Skp1 to assemble various SCF-Roc1 E3 ligases that each selectively ubiquitinate one or more specific substrates. (elsevier.com)
  • Many key activators and inhibitors of cell division are targeted for degradation by a recently described family of E3 ubiquitin protein ligases termed Skp1-Cdc53-F-box protein (SCF) complexes. (nih.gov)
  • SCF complexes physically link substrate proteins to the E2 ubiquitin-conjugating enzyme Cdc34, which catalyses substrate ubiquitination, leading to subsequent degradation by the 26S proteasome. (nih.gov)
  • The concepts of SCF ubiquitin ligase function are illustrated by analysis of the degradation pathway for the G1 cyclin Cln2. (nih.gov)
  • The conjugation of ubiquitin to proteins at lysine residues (ubiquitination), thereby targeting them to the proteosome, is essential for the degradation of many proteins in eukaryotic cells. (jneurosci.org)
  • The classical view of ubiquitination is to target proteins for degradation by a multi-subunit, ATP-dependent protease termed the proteosome ( Pickart, 2001 ). (jneurosci.org)
  • In this study, we report an E3 ubiquitin ligase soil-surface rooting 1 (SOR1), which targets a noncanonical Aux/IAA protein OsIAA26 for 26S proteasome-mediated degradation. (pnas.org)
  • SOR1 targets OsIAA26 for ubiquitin/26S proteasome-mediated degradation, whereas OsIAA9 protects the OsIAA26 protein from degradation by inhibiting the E3 activity of SOR1. (pnas.org)
  • Auxin promotes SOR1-dependent degradation of OsIAA26 by facilitating SCF OsTIR1/AFB2 -mediated and SOR1-assisted destabilization of OsIAA9 protein. (pnas.org)
  • Proteins typically are marked for proteolytic degradation by attachment of multiubiquitin chains. (pnas.org)
  • Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. (hmdb.ca)
  • Mdm2 has been shown to regulate p53 stability by targeting the p53 protein for proteasomal degradation. (thebiogrid.org)
  • Replacement of the Mdm2 RING with that of another protein (Praja1) reconstituted ubiquitination and proteasomal degradation of Mdm2. (thebiogrid.org)
  • Indeed, ~20% of all ubiquitin-proteasomal degradation is estimated to result from E3 activities of NEDD8-activated CRLs 18 . (pubmedcentralcanada.ca)
  • Surprisingly, the endogenous MKRN1 protein underwent proteasomal degradation during the late phase of HAdV-C5 infection in various human cell lines. (asm.org)
  • MKRN1 protein degradation occurred independently of the HAdV E1B55K and E4orf6 proteins. (asm.org)
  • Based on these data, we propose that the pVII protein binding promotes MKRN1 self-ubiquitination, followed by proteasomal degradation of the MKRN1 protein, in HAdV-C5-infected cells. (asm.org)
  • This mutual interaction between the pVII and MKRN1 proteins may prime MKRN1 for proteasomal degradation, because the MKRN1 protein is efficiently degraded during the late phase of HAdV-C5 infection. (asm.org)
  • Proteasome-dependent degradation of ubiquitinated proteins plays a key role in many important cellular processes. (asm.org)
  • We have previously shown that herpes simplex virus type 1 ICP0, itself a RING finger protein, induces the proteasome-dependent degradation of several cellular proteins and induces the accumulation of colocalizing conjugated ubiquitin in vivo. (asm.org)
  • It has been shown that ICP0 induces the proteasome-dependent degradation of two major components of ND10, PML itself and Sp100, particularly their isoforms that are covalently modified by the ubiquitin-like protein SUMO-1 ( 1 , 8 , 31 , 33 ). (asm.org)
  • Here, polymeric chains of ubiquitin ( Ub ) are covalently attached to proteins destined for degradation via an ATP-dependent, E1-E2-E3 conjugation cascade. (plantphysiol.org)
  • This shows that BOP proteins act as substrate adaptors in a CUL3 BOP1/BOP2 E3 ubiquitin ligase complex, targeting PIF4 proteins for ubiquitination and subsequent degradation. (elifesciences.org)
  • These findings suggest that the degradation of different PIF proteins might be controlled by specific E3 ligase complexes. (elifesciences.org)
  • However, which E3 ligases that control PIF4 degradation has so far been unknown. (elifesciences.org)
  • Beta-hydroxy-beta-methylbutyrate (HMB), a leucine metabolite, enhances the gain of skeletal muscle mass by increasing protein synthesis or attenuating protein degradation or both. (springer.com)
  • The aims of this study were to investigate the effect of HMB on molecular factors controlling skeletal muscle protein synthesis and degradation, as well as muscle contractile function, in fed and fasted conditions. (springer.com)
  • The EDL muscle was then removed, weighed and used to evaluate the genes and proteins involved in protein synthesis (AKT/4E-BP1/S6) and degradation ( Fbxo32 and Trim63 ). (springer.com)
  • P450 proteolytic turnover occurs via ER-associated degradation (ERAD) involving ubiquitin (Ub)-dependent proteasomal degradation (UPD) as a major pathway. (aspetjournals.org)
  • Ubiquitin ligases direct the transfer of ubiquitin onto substrate proteins and thus target the substrate for proteasome-dependent degradation. (asm.org)
  • Distinct SCF complexes, defined by a particular F-box protein, target different substrate proteins for degradation. (asm.org)
  • With a wide range of proteins being targeted for degradation by the proteasome, the cell overcomes the problem of specificity through a hierarchical order of Ub-conjugating machinery. (asm.org)
  • Localized protein degradation by ERAD helps generating functional subdomains in continuous ER membranes. (embopress.org)
  • This process involves the recognition of a substrate, its ubiquitination by an ER ubiquitin ligase, membrane extraction facilitated by the cytoplasmic Cdc48 ATPase, and delivery to the proteasome for degradation. (embopress.org)
  • Parkin is a ubiquitin ligase that ubiquitinates misfolded proteins targeted for the proteasome-dependent protein degradation pathway. (symptoma.com)
  • Li S, Shu B, Zhang Y, Li J, Guo J, Wang Y, Ren F, Xiao G, Chang Z, Chen D. Carboxyl terminus of Hsp70-interacting protein regulation of osteoclast formation in mice through promotion of tumor necrosis factor receptor-associated factor 6 protein degradation. (rush.edu)
  • A critical evaluation of the approaches to targeted protein degradation for drug discovery. (icr.ac.uk)
  • There is a great deal of excitement around the concept of targeting proteins for degradation as an alternative to conventional inhibitory small molecules and antibodies. (icr.ac.uk)
  • The novel E3 ubiquitin ligase Tiul1 associates with TGIF to target Smad2 for degradation. (uniprot.org)
  • Intracellular protein degradation is a tightly regulated process that in many cases is controlled by protein ubiquitylation. (eurekaselect.com)
  • Proteasome- and SCF-dependent degradation of yeast adenine deaminase upon transition from proliferation to quiescence requires a new F-box protein named Saf1p. (yeastgenome.org)
  • Here we show that cIAP2 is a ubiquitin ligase (E3) of BCL10 and targets it for degradation, inhibiting antigen receptor-mediated cytokine production. (elsevier.com)
  • The cullin 4-RING ubiquitin ligase (CRL4) family employs multiple DDB1-CUL4 associated factors substrate receptors to direct the degradation of proteins involved in a wide spectrum of cellular functions. (frontiersin.org)
  • In vitro, Cul3 promoted ubiquitination of Caenorhabditis elegans MEI-1, a katanin-like protein whose degradation requires the function of both Cul3 and BTB protein MEL-26. (elsevier.com)
  • Protein ubiquitination has been implicated recently in neural development, plasticity, and degeneration. (jneurosci.org)
  • Ubiquitination is controlled by a multi-enzyme cascade that involves E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin-ligating enzyme) activities ( Pickart, 2001 ). (jneurosci.org)
  • However, there is increasing evidence that the addition of a single ubiquitin molecule, mono-ubiquitination, is an important post-translational mechanism of modifying protein function ( Hicke, 2001 ). (jneurosci.org)
  • For instance, mono-ubiquitination of transmembrane proteins, such as receptors for trophic factors and ligand-gated ion channels, often serves as an internalization signal and thereby modulating the activity of signaling pathways ( Hicke, 2001 ). (jneurosci.org)
  • SMAD ubiquitination regulatory factors 1 and 2 (Smurf1/2) are members of the HECT domain E3 ligase family which play crucial roles in the regulation of cell cycle progression, planar cell polarity, cancer metastasis and cell apoptosis. (sdbonline.org)
  • The SCF ubiquitin ligase complex of budding yeast triggers DNA replication by catalyzing ubiquitination of the S phase cyclin-dependent kinase inhibitor SIC1. (pnas.org)
  • Moreover, hCUL1 complements the growth defect of yeast cdc53 ts mutants, associates with ubiquitination-promoting activity in human cell extracts, and can assemble into functional, chimeric ubiquitin ligase complexes with yeast SCF components. (pnas.org)
  • Whereas E2s can attach ubiquitin directly to lysine residues in a substrate, most physiological ubiquitination reactions probably require a ubiquitin ligase, or E3 ( 4 ). (pnas.org)
  • Disruption of the interaction between E2F-1 and p45SKP2 results in a reduction in ubiquitination of E2F-1 and the stabilization and accumulation of transcriptionally active E2F-1 protein. (nih.gov)
  • In addition to its well-known function in protein turnover, ubiquitination has been proposed to play roles in subcellular sorting of proteins via endocytosis and in delivery of proteins to peroxisomes, the endoplasmic reticulum and mitochondria. (genetics.org)
  • Unexpectedly, we identified a RING domain-containing E3 ligase Tul1 and its interacting proteins in the Dsc complex that are important for the ubiquitination of Cot1 and partial ubiquitination of Zrt3. (rupress.org)
  • Discussion Our data provide evidence that KOS is caused by UBE3B loss of function, and further demonstrate the impact of misregulation of protein ubiquitination on development and growth. (bmj.com)
  • Ubiquitination of substrate proteins takes place in an enzymatic reaction involving several enzymes. (uni-koeln.de)
  • We provide experimental evidence that the precursor pVII protein binding enhances MKRN1 self-ubiquitination, whereas the processed mature VII protein is deficient in this function. (asm.org)
  • In this study, we show that the HAdV-C5 histone-like core protein pVII binds to and promotes self-ubiquitination of a cellular E3 ubiquitin ligase named MKRN1. (asm.org)
  • Ubiquitination requires the E1 ubiquitin activating enzyme, an E2 ubiquitin conjugating enzyme, and frequently a substrate-specific ubiquitin protein ligase (E3). (asm.org)
  • UPD critically involves P450 protein ubiquitination by E2/E3 Ub-ligase complexes. (aspetjournals.org)
  • Here, we demonstrate that malin is a single subunit E3 ubiquitin (Ub) ligase and that its RING domain is necessary and sufficient to mediate ubiquitination. (symptoma.com)
  • protein ubiquitination This protein is involved in the pathway protein ubiquitination , which is part of Protein modification. (symptoma.com)
  • Ubiquitination is executed by a hierarchical cascade of three types of enzymes: ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s) [ 2 ]. (biomedcentral.com)
  • RING finger ubiquitin-protein ligases (E3s) are the most abundant class of E3 that mediate protein ubiquitylation (also known as ubiquitination). (nature.com)
  • Remodeling of the SCF complex-mediated ubiquitination system by compositional alteration of incorporated F-box proteins. (yeastgenome.org)
  • Through an in vitro ubiquitination assay, PHD/RING2 and PHD/RING3 domain have been reported to possess ubiquitin ligase activity and catalyze Lys48-linked poly-ubiquitination. (creative-biogene.com)
  • CRL activity is regulated by the Nedd8 post-translational modification: the ubiquitin-like Nedd8 protein is conjugated to cullins in a manner highly analogous to ubiquitination. (frontiersin.org)
  • E2 and E3 enzymes covalently link ubiquitin-like proteins (UBLs) to their protein targets. (pubmedcentralcanada.ca)
  • The hepatic endoplasmic reticulum (ER)-anchored monotopic proteins, cytochromes P450 (P450s), are enzymes that metabolize endobiotics (physiologically active steroids and fatty acids), as well as xenobiotics including therapeutic/chemotherapeutic drugs, nutrients, carcinogens, and toxins. (aspetjournals.org)
  • These U box proteins exhibited different specificities for E2 enzymes in this reaction. (elsevier.com)
  • Some U box proteins catalyzed polyubiquitination by targeting lysine residues of ubiquitin other than lysine 48, which is utilized by HECT and RING finger E3 enzymes for polyubiquitination that serves as a signal for proteolysis by the 26 S proteasome. (elsevier.com)
  • These data suggest that U box proteins constitute a third family of E3 enzymes and that E4 activity may reflect a specialized type of E3 activity. (elsevier.com)
  • Ubiquitin-protein ligase (UPL) ( E3 ) or E3 ubiquitin-protein ligase in combination with ubiquitin-conjugating enzyme (E2) causes the attachment of ubiquitin to lysine in a target protein [1] . (proteopedia.org)
  • This process is initiated by a ubiquitin-activating enzyme (E1), which activates ubiquitin by adenylation and becomes linked to it via a thiolester bond. (pnas.org)
  • Ubiquitin then is transferred to a ubiquitin-conjugating enzyme, E2. (pnas.org)
  • RING finger-dependent manner, which requires no eukaryotic proteins other than ubiquitin-activating enzyme (E1) and an ubiquitin-conjugating enzyme (E2). (thebiogrid.org)
  • We also observed that Pro-154 of Skp1, a subunit of the Skp1/Cullin-1/F-box protein (SCF)-class of E3-ubiquitin ligases, is a natural substrate of this enzyme. (semanticscholar.org)
  • Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. (rush.edu)
  • In fact, herpes simplex virus (HSV) encodes a ubiquitin ligase (E3) and a de-ubiquitinating enzyme to modify the host's ubiquitin system. (biomedcentral.com)
  • G2/M phase-specific E3 ubiquitin-protein ligase is an enzyme that in humans is encoded by the G2E3 gene. (creative-biogene.com)
  • Cullins serve as elongated scaffolds that assemble functional E3 complexes by utilizing distinct adaptors to recruit substrate receptors and the ubiquitin-charged E2 conjugating enzyme (Figure 1 ). (frontiersin.org)
  • RING protein adaptors (R) bind the ubiquitin (Ub)-charged E2 conjugating enzyme at the cullin C-terminus. (frontiersin.org)
  • Cullin family proteins bind with the RING-finger protein Roc1 to recruit the ubiquitin-conjugating enzyme (E2) to the ubiquitin ligase complex (E3). (elsevier.com)
  • The Drosophila F-box protein Slimb controls dSmurf protein turnover to regulate the Hippo pathway. (sdbonline.org)
  • This study found that the F-box protein Slimb controls dSmurf protein level to regulate the Hippo pathway. (sdbonline.org)
  • E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. (hmdb.ca)
  • Many enveloped viruses exploit the class E vacuolar protein-sorting (VPS) pathway to bud from cells, and use peptide motifs to recruit specific class E VPS factors. (rupress.org)
  • Homologous to E6AP COOH terminus (HECT) ubiquitin ligases have been implicated as cofactors for PPXY motif-dependent budding, but precisely which members of this family are responsible, and how they access the VPS pathway is unclear. (rupress.org)
  • These data indicate that specific HECT ubiquitin ligases can link PPXY motifs to the VPS pathway to induce viral budding. (rupress.org)
  • Because it remained uncertain as to precisely which HECT ubiquitin ligases mediate PPXY motif-dependent viral budding and how the class E VPS pathway is accessed by these proteins, we surveyed an array of HECT ubiquitin ligases and found that fragments of the HECT ubiquitin ligases WWP1 and WWP2 are unusually potent and specific inhibitors of viral PPXY motif function. (rupress.org)
  • The ubiquitin (Ub)-proteasome proteolytic pathway regulates the abundance of polypeptides involved in a variety of processes such as the cell division cycle, immune response, and developmental pathways (for reviews see references 5 , 12 , and 30 ). (asm.org)
  • The E3 Ubiquitin Ligase Adaptor Protein Skp1 Is Glycosylated by an Evolutionarily Conserved Pathway That Regulates Protist Growth and Development. (semanticscholar.org)
  • article{Rahman2016TheEU, title={The E3 Ubiquitin Ligase Adaptor Protein Skp1 Is Glycosylated by an Evolutionarily Conserved Pathway That Regulates Protist Growth and Development. (semanticscholar.org)
  • The ubiquitin pathway is a major route by which cells not only remove normal proteins at the appropriate time but also abnormally folded normal or mutant, cytoplasmic and membrane, proteins. (eurekaselect.com)
  • Ubiquitin ligase trapping identifies an SCF(Saf1) pathway targeting unprocessed vacuolar/lysosomal proteins. (yeastgenome.org)
  • The concentrations and functions of many cellular proteins are regulated by the ubiquitin pathway. (elsevier.com)
  • As many F-box proteins can be found in sequence databases, it appears that a host of cellular pathways will be regulated by SCF-dependent proteolysis. (nih.gov)
  • Ubiquitin-mediated proteolysis of Aux/IAA transcriptional repressors by the E3 ubiquitin ligase SCF TIR1/AFB triggers a transcription-based auxin signaling. (pnas.org)
  • Whereas genetic analysis has revealed that SIC1 proteolysis requires CDC4, G 1 cyclin proteolysis appears to depend on a distinct F-box-containing protein known as GRR1 ( 8 ). (pnas.org)
  • There are several amino acid sequence motifs associated with E3 ligases, including the RING finger, HECT (homologous to the E6-AP carboxyl terminus), F box, and U box domain ( von Arnim, 2001 ). (jneurosci.org)
  • All four characterized mdp1 mutations cause missense changes located in the hect domain of Rsp5p that is highly conserved among ubiquitin-protein ligases. (genetics.org)
  • Here, we show that PPXY-dependent viral budding is unusually sensitive to inhibitory fragments derived from specific HECT ubiquitin ligases, namely WWP1 and WWP2. (rupress.org)
  • We also show that WWP1, WWP2, or Itch ubiquitin ligase recruitment promotes PPXY-dependent virion release, and that this function requires that the HECT ubiquitin ligase domain be catalytically active. (rupress.org)
  • Finally, we show that several mammalian HECT ubiquitin ligases, including WWP1, WWP2, and Itch are recruited to class E compartments induced by dominant negative forms of the class E VPS ATPase, VPS4. (rupress.org)
  • PPXY is a consensus sequence for interaction with WW-domains, which are present in homologous to E6AP COOH terminus (HECT) ubiquitin ligases. (rupress.org)
  • T, p.Arg186stop) in UBE3B, which encodes a widely expressed HECT (homologous to the E6-AP carboxyl terminus) domain E3 ubiquitin-protein ligase. (bmj.com)
  • HERC4 belongs to the HERC family of ubiquitin ligases, all of which contain a HECT domain and at least 1 RCC1 (MIM;179710)-like domain (RLD). (creative-biogene.com)
  • The 350-amino acid HECT domain is predicted to catalyze the formation of a thioester with;ubiquitin before transferring it to a substrate, and the RLD is predicted to act as a guanine nucleotide exchange;factor for small G proteins (Hochrainer et al. (creative-biogene.com)
  • This gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. (cancer.gov)
  • In this study, we report that the giant protein HERC2, which is like E6AP a member of the HECT family of ubiquitin-protein ligases, binds to E6AP. (uni-konstanz.de)
  • There are two main groups of E3 ligases: really interesting novel genes (RING) and homologous to E6AP carboxyl terminus (HECT) proteins. (biomedcentral.com)
  • The neuronal precursor cell-expressed developmentally down-regulated 4 (Nedd4) family, comprised of nine members, is one of the main HECT E3 protein families. (biomedcentral.com)
  • They are characterized by a unique domain architecture, with an amino-terminal C2 domain, two to four protein-protein interacting WW domains and a carboxyl terminal catalytic HECT domain [ 4 ]. (biomedcentral.com)
  • SCF complexes contain a variable subunit called an F-box protein that confers substrate specificity on an invariant core complex composed of the subunits Cdc34, Skp1 and Cdc53. (nih.gov)
  • Through mass spectrometric analysis of Cdc53 associated proteins, we have identified three novel F-box proteins that appear to participate in SCF-like complexes. (nih.gov)
  • Further application of biochemical assays similar to those described here can now be used to identify regulators/components of hCUL1-based SCF complexes, to determine whether the hCUL2-hCUL5 proteins also are components of ubiquitin ligase complexes in human cells, and to screen for chemical compounds that modulate the activities of the hSKP1 and hCUL1 proteins. (pnas.org)
  • Therefore, we made a model of a CUL1-RBX1-UBC12 complex based on structures of UBC12, cullin-RBX1 complexes, and other E2s bound to other RING domain proteins ( Supplementary Fig. 1 ) 2 - 4 , 7 . (pubmedcentralcanada.ca)
  • SCF complexes are a family of ubiquitin ligases composed of a common core of components and a variable component called an F-box protein that defines substrate specificity. (asm.org)
  • Using Saccharomyces cerevisiae as a model system, we demonstrate that overproduction of polypeptides corresponding to the amino terminus of the F-box proteins Cdc4p and Met30p results in specific inhibition of their SCF complexes. (asm.org)
  • SCF (Skp1-Cul1/Cdc53-F-box) complexes represent a major family of Ub ligases that are evolutionarily conserved, being present in all eukaryotic taxa (for reviews see references 6 , 7 , 19 , and 30 ). (asm.org)
  • Components from yeast and human SCF complexes produced in insect cells have been demonstrated previously to possess Ub ligase activities ( 10 , 16 , 37 , 43 ). (asm.org)
  • Thus, SCF complexes define a family of E3 ligases that may be distinguished by a particular F-box protein, which in turn determines substrate specificity for that complex. (asm.org)
  • These events are coordinated by ER membrane‐embedded protein complexes that have at their core an ubiquitin ligase. (embopress.org)
  • Besides misfolded proteins, Hrd1 and Doa10 complexes were shown to degrade some folded, functional proteins but in a regulated manner, only upon a specific signal. (embopress.org)
  • Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes. (rush.edu)
  • Genetic alterations to components of these E3 complexes that result in loss of function (such as FBW7, CDH1 and CDC20) or gain of function (such as SKP2 and β-transducin repeat-containing protein (β-TrCP)) are implicated in the development of cancer. (nature.com)
  • Ligases come in many forms, from single proteins to very large multiprotein complexes. (eurekaselect.com)
  • UPL contains an thioester-forming cysteine which catalyzes the transfer of ubiquitin from E2 to a substrate lysine. (proteopedia.org)
  • E3s have been implicated in substrate recognition and, in one case, transfer of ubiquitin from E2 to a substrate via an E3-ubiquitin-thiolester intermediate ( 5 ). (pnas.org)
  • abstract = "The pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphomas is associated with independent chromosomal translocations that lead to the upregulation of either BCL10 or MALT1 or the generation of a fusion protein, cIAP2-MALT1. (elsevier.com)
  • Our study demonstrated that the Dsc complex can function at the vacuole to regulate the composition and lifetime of vacuolar membrane proteins. (rupress.org)
  • Whereas other red light-hypersensitive mutants accumulate phyA protein similar to or higher than the wild type in light, the lrb1 lrb2 mutants accumulate less, suggesting that LRB1/2 also positively regulate phyA levels in a phyB/D-dependent manner. (plantphysiol.org)
  • The key components that regulate substrate ubiquitylation are the ubiquitin-protein ligases. (eurekaselect.com)
  • Furthermore, G2E3 could influence proteins which regulate the expression of apoptotic genes. (creative-biogene.com)
  • The G protein β subunit functions as an adaptor subunit for an E3 ligase that ubiquitylates the G protein-coupled receptor kinase GRK2. (sciencemag.org)
  • Characterization of a cytoplasmic glucosyltransferase that extends the core trisaccharide of the Toxoplasma Skp1 E3 ubiquitin ligase subunit. (semanticscholar.org)
  • Keap1 assembles into a functional E3 ubiquitin ligase complex with Cul3 and Rbx1 that targets multiple lysine residues located in the N-terminal Neh2 domain of Nrf2 for ubiquitin conjugation both in vivo and in vitro. (asm.org)
  • The NEDD8-modified CUL1 assembles with SKP1-F-box protein-substrate, RBX1 binds a ubiquitin-charged E2 such as UBCH5 or CDC34, and ubiquitin is ligated to a substrate 15 , 16 . (pubmedcentralcanada.ca)
  • Finally, RBX1 binds another ubiquitin-charged CDC34, and ubiquitin is transferred to Lys48 on a substrate-linked ubiquitin. (pubmedcentralcanada.ca)
  • Nrf2 binds DNA as a heterodimer with one of several small Maf proteins and is a potent activator of ARE-dependent transcription. (asm.org)
  • G2-specific E3 ligase (G2E3) was originally identified in a global gene expressing profiling with the GenBank reference KIAA1333 when Crawford et al . (creative-biogene.com)
  • We previously identified ZNRF1/nin283, a protein with a unique, evolutionarily conserved C-terminal domain containing a juxtaposed zinc finger/RING finger combination. (jneurosci.org)
  • MDP1 is identical to RSP5 , which encodes ubiquitin-protein ligase, and mdp1 mutations are suppressed by high copy expression of ubiquitin. (genetics.org)
  • The surface interacting residues of UPL and the acceptor ubiquitin are shown here [7] . (proteopedia.org)
  • UPL XIAP or X-linked Inhibitor of Apoptosis Protein stops apoptosis induced by viral infection or by overproduction of caspases. (proteopedia.org)
  • Here, we show that hCUL1 associates with hSKP1 in vivo and directly interacts with both hSKP1 and the human F-box protein SKP2 in vitro , forming an SCF-like particle. (pnas.org)
  • Moreover, we found that BOP proteins physically interact with both PIF4 and CULLIN3A and that a CULLIN3-BOP2 complex ubiquitinates PIF4 in vitro. (elifesciences.org)
  • Furthermore, we provide evidence that HERC2 stimulates the ubiquitin-protein ligase activity of E6AP in vitro and within cells and that this stimulatory effect does not depend on the ubiquitin-protein ligase activity of HERC2. (uni-konstanz.de)
  • Much knowledge of RING E3s derives from studies of the modular multiprotein cullin-RING ligases (CRLs) 1 . (pubmedcentralcanada.ca)
  • How RING E3 ligases mediate E2-to-substrate ubiquitin-like protein (UBL) transfer remains unknown. (pubmedcentralcanada.ca)
  • Six mammalian U box proteins have now been shown to mediate polyubiquitination in the presence of E1 and E2 and in the absence of E3. (elsevier.com)
  • The selective breakdown of short-lived regulatory proteins is a key feature of many signal transduction pathways, thus providing a mechanism to enhance or quench output when repressors or activators are the respective targets. (plantphysiol.org)
  • Ubiquitin-Protein Ligases - Novel Therapeutic Targets? (eurekaselect.com)
  • For E3 ubiquitin-protein ligase parkin see Parkin . (proteopedia.org)
  • Khasnavis S, Pahan K. Cinnamon treatment upregulates neuroprotective proteins Parkin and DJ-1 and protects dopaminergic neurons in a mouse model of Parkinson's disease. (rush.edu)
  • MDP3 is identical to PAN1 , which encodes a protein involved in initiation of translation and actin cytoskeleton organization. (genetics.org)
  • However, upstream pathways governing BRAF kinase activity and protein stability remain undefined. (duke.edu)
  • The nature of the protein kinase(s) and the ubiquitin E3 ligase(s) involved in the regulation of PIF stability in response to light have just started to be explored. (elifesciences.org)
  • Investigation of the downstream effector pathways for these growth factors has identified molecules involved in the progression of cardiac hypertrophy and heart failure, including phosphoinositide 3-kinase (PI3K) and Akt (Protein Kinase B). MG53, a tripartite motif (TRIM) protein family member designated as TRIM72, is highly expressed in skeletal and cardiac muscle and is known to have cardioprotective effects through modulation of PI3K signaling mechanisms. (ahajournals.org)
  • The cell cycle is regulated by the S phase kinase-associated protein 1 (SKP1)-cullin 1 (CUL1)-F-box protein (SCF) and anaphase-promoting complex/cyclosome (APC/C) multisubunit RING finger E3s. (nature.com)
  • however, few E3 ubiquitin ligases that target membrane proteins (e.g. (jneurosci.org)
  • However, very little is known about mechanisms that govern the regulation of its membrane proteins. (rupress.org)
  • The endoplasmic reticulum ( ER ) plays a central role in the biogenesis of most membrane proteins. (embopress.org)
  • The LD monolayer is often continuous with the membrane of the ER allowing certain membrane proteins to diffuse between the two organelles. (embopress.org)
  • The endoplasmic reticulum (ER) plays a central role in the biogenesis of membrane and secretory proteins, facilitating the folding and the post‐translational modifications necessary for their function (Braakman & Hebert, 2013 ). (embopress.org)
  • The widespread expression of ZNRF proteins in the nervous system along with their involvement in exocytosis in presynaptic terminals that we demonstrate here suggests that they may participate in the regulation of proteins involved in presynaptic exocytosis and/or synaptic vesicle recycling. (jneurosci.org)
  • The encoded protein plays a role in multiple cellular processes including erythroid and lymphoid cell differentiation and the regulation of immune responses. (cancer.gov)
  • Petroski MD and Deshaies RJ (2005) Function and regulation of cullin-RING ubiquitin ligases. (yeastgenome.org)
  • Human homologues of yCDC34 and ySKP1 have been reported ( 9 , 10 ), and F-box-containing proteins like CDC4 and GRR1 have been identified in many eukaryotes ( 11 ). (pnas.org)
  • Taken together, these data suggest that hCUL1 functions as part of an SCF ubiquitin ligase complex in human cells. (pnas.org)
  • The APC/C E3 Ligase Complex Activator FZR1 Restricts BRAF Oncogenic Function. (duke.edu)
  • In this report, we demonstrate that Keap1 functions as a substrate adaptor protein for a Cul3-dependent E3 ubiquitin ligase complex. (asm.org)
  • Our results suggest that the ability of Keap1 to assemble into a functional E3 ubiquitin ligase complex is the critical determinant that controls steady-state levels of Nrf2 in response to cancer-preventive compounds and oxidative stress. (asm.org)
  • Members of the Bric-a-Brac/Tramtrack/Broad Complex ( BTB ) family direct the selective ubiquitylation of proteins following their assembly into Cullin3-based ubiquitin ligases. (plantphysiol.org)
  • Regarding viral assembly and release, several Nedd4 family E3 ligases act to link the endosomal sorting complex required for transport (ESCRT) system and viral proteins [ 7 ]. (biomedcentral.com)
  • Many RING finger E3s have roles in processes that are central to the maintenance of genomic integrity and cellular homeostasis, such as the anaphase promoting complex/cyclosome (APC/C), the SKP1-cullin 1-F-box protein (SCF) E3s, MDM2, BRCA1, Fanconi anaemia proteins, CBL proteins, von Hippel-Lindau tumour suppressor (VHL) and SIAH proteins. (nature.com)
  • This diagram displays the protein subunits (blue) of the complex and how they interact with each other. (yeastgenome.org)
  • This table lists all participants of the complex (proteins, small molecules, nucleic acids, etc.) and their respective stoichiometry. (yeastgenome.org)
  • Several studies suggest that Nedd4-like ubiquitin ligases play roles in viral budding. (rupress.org)
  • We have previously reported HSV type 2 (HSV-2) tegument protein UL56 as a putative adaptor protein of neuronal precursor cell-expressed developmentally down-regulated 4 (Nedd4) E3 ligase, which has been shown to be involved in protein sorting and trafficking. (biomedcentral.com)
  • In addition to these two proteins, the HSV type 2 (HSV-2) tegument protein UL56 was identified as a putative adaptor protein of Nedd4 E3 ligase [ 13 ]. (biomedcentral.com)
  • The molecular details of how protein VII acts as a multifunctional protein have remained to a large extent enigmatic. (asm.org)
  • Here we designate ZNRF proteins as a family of molecules by the identification of a second mammalian protein, ZNRF2, which is highly similar to ZNRF1 in the zinc finger-RING finger region. (jneurosci.org)
  • Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. (thebiogrid.org)
  • We now report that Mdm2 is a ubiquitin protein ligase (E3) for p53 and that its activity is dependent on its RING finger. (thebiogrid.org)
  • Recent crystallographic analyses have confirmed a wealth of genetic and biochemical evidence by demonstrating that the ∼40-amino-acid F-box motif links the F-box protein with the common SCF components by binding Skp1p ( 35 , 49 ). (asm.org)
  • Here we report the identification of several cellular proteins interacting with the precursor pVII protein. (asm.org)
  • We conclude that ICP0 has the potential to act as an E3 ubiquitin ligase during viral infection and to target specific cellular proteins for destruction by the 26S proteasome. (asm.org)
  • Since the proteasome inhibitor MG132 interferes with the ability of ICP0 to stimulate viral infection and reactivation from quiescence ( 14 ), it is likely that these effects on cellular proteins reflect a major biological function of ICP0. (asm.org)
  • Levels of phyB/D proteins but not their messenger RNAs are abnormally high in light-grown lrb1 lrb2 plants, implying that their light-dependent turnover is substantially dampened. (plantphysiol.org)
  • Together, these data show that the BTB ubiquitin ligases assembled with LRB1/2 function redundantly as negative regulators of photomorphogenesis, possibly by influencing the turnover of phyB/D. (plantphysiol.org)
  • The ubiquitin system functions in a variety of cellular processes including protein turnover, protein sorting and trafficking. (biomedcentral.com)
  • The ubiquitin system is a key regulatory mechanism for a variety of cellular processes: protein turnover, protein sorting and trafficking, signal transduction and cell-cycle control [ 1 ]. (biomedcentral.com)
  • More recently, it has become clear that a large number of proteins containing RING finger motifs function as E3 ligases, with the RING finger motif itself serving to recruit specific E2s ( Pickart, 2001 ). (jneurosci.org)
  • and/or peptide motifs in cellular and viral proteins (see below). (rupress.org)
  • The RING finger is a zinc-binding protein domain that was initially characterized as a protein interaction domain ( Borden, 1998 ). (jneurosci.org)
  • These abnormalities often arise from the loss of a key protein-protein interaction. (eurekaselect.com)
  • Taken together, our results expand the functional repertoire of the HAdV-C5 precursor pVII protein in lytic virus infection and highlight MKRN1 as a potential common target during different virus infections. (asm.org)
  • One class of E3 ubiquitin ligases has been shown to contain a common zinc-binding RING finger motif. (asm.org)
  • Inside the core, HAdV DNA associates with the viral proteins V, VII, Mu, terminal protein, and DNA-dependent adenovirus proteinase (Avp) ( 3 ). (asm.org)
  • Although a few have been identified to be involved in important biological pathways, such as the cell division cycle and coordinating cellular responses to changes in environmental conditions, the role of the overwhelming majority of F-box proteins is not clear. (asm.org)
  • These proteins are linked to a fourth variable protein component, called the F-box protein, which is responsible for substrate recognition. (asm.org)
  • Nonetheless, to date none of the 7 RBX1 structures is in a conformation demonstrating any of its UBL ligase functions 7 , 8 , 13 , 19 . (pubmedcentralcanada.ca)
  • SCF is composed of three proteins-ySKP1, CDC53 (Cullin), and the F-box protein CDC4-that are conserved from yeast to humans. (pnas.org)
  • The U box is a domain of ∼70 amino acids that is present in proteins from yeast to humans. (elsevier.com)
  • We suggest that in vivo there exists a potentially large number of BCR3 (BTB-Cul3-Roc1) E3 ubiquitin ligases. (elsevier.com)
  • CYLD, an ubiquitin hydrolase, has an expanding repertoire of regulatory roles in cell signalling and is dysregulated in a number of cancers. (icr.ac.uk)
  • The ubiquitin-proteasome system has numerous crucial roles in physiology and pathophysiology. (nature.com)
  • The largest family of E3s comprises the RING cohort, which bind both a UBL-loaded E2 and a protein substrate targeted for UBL transfer 1 . (pubmedcentralcanada.ca)
  • Our recent studies also show that TRIM72 can form heterodimers with other members of the TRIM family proteins that contains approximately 70 different members in the human genome. (ahajournals.org)
  • Many TRIM family proteins are known to act as E3 ubiquitin ligases that target the ubiquitin proteasome to particular proteins. (ahajournals.org)