Lysine ubiquitin protein ligase complexes. Medical search. Frequent questions

The RNF168 E3 ubiquitin ligase catalyzes the mono-ubiquitination of histone H2A at lysine (K)13/15 (mUb-H2A), forming a binding module for DNA repair proteins. (nih.gov)
16678110 ). It is also part of a SWI/SNF chromatin remodelling complex that consists of BAF250, elongin C (Elo C) and cullin 2 (Cul2) and mediates H2B lysine 120 ubiquitination. (iiserpune.ac.in)
This active complex may provide multiple E2 active sites, enabling efficient ubiquitination of substrates. (rcsb.org)
The E3 ubiquitination step determines the overall specificity for ubiquitination of the target protein, and the activated ubiquitin is usually transferred to a lysine residue in the substrate. (bmbreports.org)
In human cells, Nedd4 overexpression enhances α-synuclein ubiquitination and clearance by a lysosomal process requiring components of the endosomal-sorting complex required for transport. (ox.ac.uk)
Review of the Structure of the Arabidopsis PEX4-PEX22 Peroxin Complex-Insights Into Ubiquitination at the Peroxisomal Membrane. (ruhr-uni-bochum.de)
Regulation of peroxisomal matrix protein import by ubiquitination. (ruhr-uni-bochum.de)
By mobilizing the nascent chain, CAT tailing can expose lysine residues that are hidden in the exit tunnel, thereby supporting efficient ubiquitination. (escholarship.org)
During this 2-step process, the ER transmembrane E3 ligase TRIM13 undergoes auto-ubiquitination via lysine 63 (K63) linkage chains and acts as a ligand for the autophagic receptor SQSTM1/p62 (sequestosome 1). (nih.gov)
Like many proteins, the function of PTEN is controlled in part by ubiquitination-the covalent ligation of units of the small regulatory protein ubiquitin. (rupress.org)
PcG complex one is then recruited with the recognition of methylated H3K27 by the chromodomain of Cbx loved ones and in duces mono ubiquitination of histone H2A at lysine 119, which silences transcription. (gabasignaling.com)
Numerous E3 ubiquitin ligases, which facilitate the ubiquitination of specific substrates, have been shown to control G1/S. In this chapter, we will discuss components in the ubiquitin proteasome system that are implicated in G1/S control, how these enzymes are interconnected, gaps in our current knowledge, and the potential role of these pathways in the cancer cycle and disease proliferation. (intechopen.com)
For IκBα, the stimulus-induced phosphorylation at serines 32 and 36 renders the inhibitor a target for ubiquitination at lysines 21 and 22, resulting in degradation. (justia.com)
Similarly, phosphorylation of IκBβ at serines 19 and 23 renders the inhibitor a target for ubiquitination at lysine 9. (justia.com)
Ubiquitination targets proteins for degradation and is a potent regulator of cellular protein function. (embl-heidelberg.de)
Ubiquitin is a small protein that can be attached to other proteins through a process called ubiquitination, where it acts as a signal to recruit the cell's protein degradation machinery. (cam.ac.uk)
Ubiquitin is normally attached to protein lysine residues, but serine, threonine, cysteine and N-terminal ubiquitination can also occur. (cam.ac.uk)
To directly test if TRIM21 N-terminal ubiquitination is required for TRIM21 function, Leo Kiss in collaboration with Jonas Weidenhausen in Irmgard Sinning's lab at the University of Heidelberg developed a method to modify the TRIM21 protein N-terminus with an acetyl group to prevent its self-ubiquitination. (cam.ac.uk)
Surprisingly, RhoA (but not Rac1, Cdc42, or p190RhoGAP) protein levels increased due to reduced RhoA ubiquitination mediated by the adaptor protein CCM2 (cerebral cavernous malformation 2) and the E3 ubiquitin ligase Smurf1 and subsequent proteasomal degradation. (cytoskeleton.com)
CRLs are a large superfamily of E3s that are responsible for the ubiquitination of multiple substrate proteins including several that are involved in the regulation of normal cellular function as well as some that have been MifaMurtide shown to be associated with cancer (Table 1). (researchassistantresume.com)

E2 ubiquitin-conjugating enzymes catalyze the attachment of ubiquitin to lysine residues of target proteins. (rcsb.org)
Purified Nedd4 recognizes the carboxyl terminus of α-synuclein (residues 120-133) and attaches K63-linked ubiquitin chains. (ox.ac.uk)
This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. (thermofisher.com)
Positively charged residues at the entrance to the vestibule function as a selectivity filter that uses charge-repulsion to reject mitochondrial TA proteins. (stanford.edu)
Mutant ubiquitin, in which all lysine residues were replaced by arginine was present in lane 7. (biomedcentral.com)
The finding that Trim-Away degrades proteins by directly ubiquitinating them led the researchers to ask which residues ubiquitin is attached to. (cam.ac.uk)
Surprisingly, they found that if they removed all lysine residues from a protein and blocked its N-terminus by acetylation the protein was still efficiently degraded by Trim-Away. (cam.ac.uk)

In this study, we reveal that an RNF168-governed signaling pathway is responsible for localizing the BRCA1-P complex to DNA damage. (nih.gov)

The covalent attachment of ubiquitin to a target protein is catalyzed by the sequential action of a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2), and a ubiquitin ligase (E3). (bmbreports.org)
Covalent attachment, via an isopeptide bond, to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by E3 ligases such as PIAS1-4, RANBP2 or CBX4. (thermofisher.com)
Degradation of a protein via the ubiquitin pathway proceeds by two discrete and successive steps: (a) covalent attachment of multiple ubiquitin molecules to the protein substrate, and (b) degradation of the targeted protein by the 26S proteasome complex. (justia.com)
Ubiquitin-directed degradation involves two broad steps: tagging the target protein via covalent attachment of several ubiquitin molecules (polyubiquitylation), and then subsequent recognition and degradation of the tagged protein by the proteasome. (tissueandcells.com)
Ubiquitylation describes the covalent attachment of a small 76-amino acid protein, ubiquitin, to other proteins. (ddw-online.com)

Cullin 3-RING complex consists of Cullin 3 protein, RING-box protein 1 (RBX1), which recruits the ubiquitin-conjugating enzyme (E2), and a Bric-a-brac/Tramtrack/Broad (BTB) protein, a substrate recognition subunit. (wikipedia.org)
One such component, a single E1 enzyme, carries out activation of ubiquitin. (justia.com)
88:7351, 1991) and it appears that each E2 enzyme can act with one or more E3 proteins (Nuber et al. (justia.com)
The recruited E3 ligase then mediates the transfer of ubiquitin from an E2 enzyme to the POI. (tissueandcells.com)
During tagging (also called conjugation), an E3 ubiquitin ligase transfers ubiquitin from a recruited E2 ubiquitin-conjugating enzyme to a lysine residue on the target protein via an isopeptide bond. (tissueandcells.com)
TRIM21 is a ubiquitin ligase enzyme, meaning that it can catalyse the attachment of ubiquitin molecules to proteins. (cam.ac.uk)
Biochemistry of Neddylation NEDD8 is an 81-amino acid protein with 9 kDa relative molecular mass and is 60% identical and 80% homologous to ubiquitin.15 16 NEDD8 has a dedicated E1-activating enzyme (AppBp1/UBA3 MifaMurtide or NAE)17 and E2-conjugating enzymes (UBC12 UBE2F)18 and is essential for the enzymatic activity of the CRL family of E3 ligases 12 through conjugation to the cullin scaffold. (researchassistantresume.com)

Deneddylation is conducted by an eight-subunit CSN complex which mediates the cleavage of the isopeptidic bond between NEDD8 and cullin protein. (wikipedia.org)
In this study, we showed that the N-degron pathway mediates ubiquitin (Ub)-dependent reticulophagy. (nih.gov)
We previously demon strated that Scmh1 mediates a molecular interaction of PcG com plex one with geminin and that PcG complex one acts as an selleck chemicals E3 ubiquitin ligase for geminin to sustain the hematopoietic stem cell exercise. (gabasignaling.com)
This gene encodes a member of a family of E3 small ubiquitin-related modifier (SUMO) ligases that mediates the attachment of a SUMO protein to proteins involved in nuclear transport, transcription, chromosome segregation and DNA repair. (nih.gov)

Added ubiquitin moieties to the lysine residue by CRLs then target the protein for the proteasomal degradation. (wikipedia.org)
Activation of the complex is regulated by the attachment of the ubiquitin-like protein NEDD8 to a conserved Lys residue in the cullin-homology domain, the process called neddylation. (wikipedia.org)
Indeed, biochemical assays support a model in which the self-assembled UbcH5b~Ub can serve as a bridge for the gap between the lysine residue of the substrate and the catalytic cysteine of E2. (rcsb.org)
2010). This post-translational modification is tightly controlled by an enzymatic cascade involving several enzymes (E1, E2, and E3) and occurs through either an isopeptide bond between the C-terminal Glycyl residue of Ub and the epsilon amino group of a Lysyl residue on a target protein or through a peptide bond between the C-terminal Glycyl residue of Ub and the N-terminal amine on a further Ub. (ubiquigent.com)

2012). The functionality of Ub chains is most commonly associated with their attachment to substrate proteins but there is also evidence that they may also play a role in cellular signalling as free chains (Braten et al. (ubiquigent.com)

Cullin 3 is a component of Cullin-RING E3 ubiquitin ligases complexes (CRLs) which are involved in protein ubiquitylation and represent a part of ubiquitin-proteasome system (UPS). (wikipedia.org)
Finley, D. Recognition and processing of ubiquitin-protein conjugates by the proteasome. (nature.com)
Beyond the organelle dynamics, the constant interaction with the ubiquitin-proteasome-system (UPS) has become an emerging aspect of healthy mitochondria. (hindawi.com)
If the ubiquitin-proteasome system is overwhelmed or unavailable, CAT-tailed nascent chains can aggregate in the cytosol or within organelles like mitochondria. (escholarship.org)
Ubiquitin Proteasome System Current Insights into Mechanism Cellular Regu. (intechopen.com)
Specifically, the boundary between G1 and S-phase is tightly regulated by the ubiquitin proteasome system. (intechopen.com)
After dissociation of the ternary complex the ubiquitylated POI is removed by the proteasome degradation machinery. (tissueandcells.com)
First described in 2001, PROTACs are designed to degrade target proteins by redirecting the ubiquitin-proteasome system. (tissueandcells.com)
The resulting polyubiquitin chain flags the target protein for degradation by the proteasome. (cisbio.jp)
The resulting ternary complex catalyzes polyubiquitination of the target protein, tagging it for degradation by the proteasome. (cisbio.jp)
The ubiquitin-proteasome system (UPS) is in charge of the majority of protein turnover in eukaryotic cells and plays an integral role in maintaining cellular protein homeostasis. (researchassistantresume.com)

CRL complex containing Cullin 3 controls the activity of Na+ Cl− cotransporter (NCC) in the kidney by regulating the proteasomal degradation of With-no-lysine [K] kinases WNK1 and WNK4. (wikipedia.org)
Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation. (nature.com)
Polymeric SUMO1 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins. (thermofisher.com)
In contrast to traditional small-molecule-mediated pharmacology, PROTACs effectively act as catalysts, accelerating the ubiquitylation and proteasomal degradation processes of the target protein, which in turn may result in different pharmacodynamic consequences compared with traditional inhibition. (tissueandcells.com)
Ubiquitin itself can direct its targets to a number of different fates, including proteasomal degradation and membrane protein transport. (enzolifesciences.com)

Another protein that interacts with cullin is CAND1 which binds to deneddylated form of cullin protein and disrupts the interaction between cullin and other subunits of the complex leading to inhibition of the E3 ubiquitin ligase activity. (wikipedia.org)
The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box). (thermofisher.cn)
olycomb group proteins are subunits of PcG complex 1 and 2 and other complexes and regulate the transcription of developmental regulators, which include Hox genes. (gabasignaling.com)
The activity of CDKs is controlled by their binding to coactivator subunits termed Cyclins, as well as by CDK inhibitory proteins termed CKIs. (intechopen.com)
The LUBAC complex has been identified as an E3 ligase consisting of three subunits - SHARPIN, HOIL-IL and HOIP - which linearly ubiquitylates NEMO leading to activation of the IKK kinases (Tokunaga et al. (ubiquigent.com)
Examples include targets such as disease-relevant scaffolding proteins, subunits of larger functional complexes and other non-enzymatic proteins such as transcription factors or RNA-binding proteins. (tissueandcells.com)

The conserved family of Transcription Intermediary Factors (TIF1) proteins consists of key transcriptional regulators that control transcription of target genes by modulating chromatin state. (elifesciences.org)
We list the DNA repair genes and related E3 ligases. (bmbreports.org)
The 11 genes with a high frequency of mutation differed between cancers, and mutations in many DNA DSB repair E3 ligase genes were related to a higher total mutation burden. (bmbreports.org)
DNA DSB repair E3 ligase genes are involved in tumor suppressive or oncogenic functions, such as RNF168 and FBXW7, by assisting the functionality of these genomic alterations. (bmbreports.org)
However, given that tomato specialized metabolism is highly complex, in order to identify the novel genes involved in aspects of fruit quality that are associated with these metabolites still requires considerable research effort. (biomedcentral.com)
The key role of a PROTAC molecule is to drive the formation of the ternary complex (protein target-PROTAC-E3 ligase) by bringing a specific E3 ligase (encoded by one of the more than 600 E3 ligase human genes)into proximity to the defined target protein, thus catalysing the ubiquitylation process. (tissueandcells.com)

This review focuses on an up-to-date understanding of the functions of E3 ligases in cancers and debates the perspectives of cancer cells that rely on inhibition or activation of ubiquitylation of target proteins. (bmbreports.org)
PROTAC pathways to degrade target proteins: from cell entry to target degradation. (cisbio.jp)

Cullin-RING E3 ubiquitin ligases are involved in many cellular processes responsible for cell cycle regulation, stress response, protein trafficking, signal transduction, DNA replication, transcription, protein quality control, circadian clock and development. (wikipedia.org)
Husnjak, K. & Dikic, I. Ubiquitin-binding proteins: decoders of ubiquitin-mediated cellular functions. (nature.com)
Despite its small genome and limited number of effector proteins, Ehrlichia efficiently establishes an intracellular infection and avoids immune defenses in vertebrate and invertebrate hosts through complex molecular and cellular reprogramming strategies. (frontiersin.org)
Cells express a pool of thousands of different proteins that need to be tightly controlled for proper cellular structure, organization, and function. (hindawi.com)
The small protein ubiquitin plays a vital role in virtually all aspects of cellular life. (intechopen.com)
We recently described the structure of M. musculus RNF213 (PDB: 6TAX) and characterized its enzymatic activity, revealing it as a large monomeric protein with a functional dynein-like AAA (ATPases Associated with diverse cellular Activities) core that exists alongside a novel E3 ligase module ( 16 ). (biorxiv.org)
The cellular stress and subsequent DNA damage signaling imposed by hyperactivity of these multiple molecular systems in addition to aberrant circadian rhythmicity lead to extensive protein aggregation such as α-synuclein pre-formed fibrils (α-Syn PFFs), suggesting a specific molecular pathway linking circadian rhythmicity, PARP1/E3 ligase activity, and Parkinson's disease. (frontiersin.org)
Alpha CETSA ® (Cellular Thermal Shift assays, from Pelago Bioscience) kits provide simple & rapid solutions to assess PROTAC compound permeability and bind to the targeted endogenous protein in various cellular models. (cisbio.jp)
Post-translational modification by ubiquitin and ubiquitin-like proteins (Ubls) is an essential cellular regulatory mechanism, allowing rapid and reversible control of a target protein's function by altering its half-life, sub-cellular localization, enzymatic activity, protein-protein interactions, or other properties. (enzolifesciences.com)
Leo James' group in the LMB's PNAC Division has now identified surprising protein modifications that underly Trim-Away protein degradation technology, which may explain its broad applicability to deplete almost any cellular protein. (cam.ac.uk)
Surprisingly, however, in infection and Trim-Away experiments carried out together with Tyler Rhinesmith, he found that the N-terminally acetylated TRIM21 was still able to efficiently degrade antibody-bound cellular proteins and invading pathogens. (cam.ac.uk)
This mode of action may also explain why Trim-Away technology can be used to degrade a wide-range of cellular proteins. (cam.ac.uk)
The mission of the Pittsburgh Center for HIV Protein Interactions (PCHPI) is to understand HIV maturation and the early cellular events of HIV infection by characterizing HIV-host cell protein interactions/complexes at a high-resolution, molecular level. (pitt.edu)
We specialize in the production of purified proteins and easy-to-use kits to study biochemical and cellular processes. (cytoskeleton.com)
Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. (cusabio.com)

In the ATP-bound form, it has a low affinity for substrate proteins. (cusabio.com)
However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. (cusabio.com)

PROteolysis TArgeting Chimeras (PROTACs) are small two-headed (heterobifunctional) molecules that hijack the cell's protein degradation machinery to irreversibly destroy the target. (cisbio.jp)

Specific recognition of linear ubiquitin chains by NEMO is important for NF-B activation. (nature.com)
In fact the ubiquitin-chain binding protein NEMO (Nuclear factor-κB (NF-κB) essential modulator) shows preference for linear ubiquitin chains even over the similarly structured Lys-63 chains (Kensche et al. (ubiquigent.com)

2012). In contrast to Lys-48 di-ubiquitin both Lys-63 and linear di-ubiquitin adopt open conformations with no contact between the ubiquitin molecules (Komander et al. (ubiquigent.com)
Proteolysis-targeting chimera (PROTAC) molecules are bifunctional: one end binds to a protein of interest (POI) and the other end binds to an E3 ligase to form a ternary complex. (tissueandcells.com)

Abstract ARAP2 is an Arf GAP that has previously been reported to affect focal adhesions (FAs) by regulating Arf6 and integrin trafficking and to bind to the adaptor proteins APPL1. (bio2009.org)

The hierarchical recruitment model proposes that PcG com plex two is recruited rst to target loci and methylates histone H3 at lysine 27. (gabasignaling.com)

A protein complex that includes a ubiquitin-protein ligase and other proteins that may confer substrate specificity on the complex. (systemsbiology.net)
The specificity of the proteins is determined by the sequences outside the repeats themselves. (embl.de)
Di-ubiquitin cleavage assay: The capacity of the di-ubiquitin substrate to be cleaved was tested using a promiscuous - with respect to ubiquitin linkage specificity - deubiquitylase (GST-USP2). (ubiquigent.com)
E3 ubiquitin-protein ligases determine the substrate specificity for ubiquitylation and have been classified into HECT and RING-finger families. (embl-heidelberg.de)
PTEN is a protean protein with a dual-specificity cytosolic lipid and tyrosine phosphatase activity. (biomedcentral.com)
Each PROTAC consists of a linker with a ligand on one end to confer target specificity, and a different ligand on the other end to engage the cell's ubiquitin system. (cisbio.jp)

BRCA1 promotes homologous recombination (HR), in part, through its interaction with PALB2, and the formation of a larger BRCA1-PALB2-BRCA2-RAD51 (BRCA1-P) complex. (nih.gov)
Cell 75:495, 1993), and a series of unique E6-AP homologous proteins have been identified (Huibregtse et al. (justia.com)

FAs are structures composed of clustered transmembrane proteins called integrins that bind to the extracellular matrix and link to the actin cytoskeleton and control cell migration, proliferation, survival and differentiation (Gardel et al. (bio2009.org)

Cleavage Under Targets & Release Using Nuclease (CUT&RUN) has swiftly become the preferred procedure over the past few years for genomic mapping and detecting interactions between chromatin and its bound proteins. (bvsalud.org)

Cullin 3 is a protein that in humans is encoded by the CUL3 gene. (wikipedia.org)
Together, our work identified Bonus as a regulator of tissue-specific gene expression and revealed the importance of SUMOylation as a regulator of complex formation in the context of transcriptional repression. (elifesciences.org)
Recruitment of the linear ubiquitin chain assembly complex stabilizes the TNF-R1 signaling complex and is required for TNF-mediated gene induction. (nature.com)
Results were correlated with immunoreactivity for USP7 (herpes virus-associated ubiquitin-specific protease 7) and SUMO2/3 (small ubiquitin-related modifier protein 2/3) as well as PTEN and p53 FISH gene status. (biomedcentral.com)
Naturally occurring mutations in this gene, that abolish the SUMO ligase activity, are associated with primordial dwarfism and extreme insulin resistance. (nih.gov)

Ikeda, F. & Dikic, I. Atypical ubiquitin chains: new molecular signals. (nature.com)
In Parkinson disease, α-synuclein accumulates in intraneuronal inclusions often containing ubiquitin chains. (ox.ac.uk)
In the former (isopeptide bond-linked) case the substrate protein may either be ubiquitin itself - thus leading to the generation of poly-ubiquitin chains - or another target protein (Fushman et al. (ubiquigent.com)
The binding of the adaptor protein NEMO to ubiquitin chains appears to be critical to the linking of upstream ubiquitin signals with the activation of this complex and subsequently the NF-κB pathway. (ubiquigent.com)
Braten O, Shabek N, Kravtsova-Ivantsiv Y, Ciechanover A (2012) Generation of free ubiquitin chains is upregulated in stress, and facilitated by the HECT domain ubiquitin ligases UFD4 and HUL5. (ubiquigent.com)
2012) Analysis of NF-kappaB essential modulator (NEMO) binding to linear and lysine-linked ubiquitin chains and its role in the activation of NF-kappaB. (ubiquigent.com)

Regulation of the Tumor-Suppressor Function of the Class III Phosphatidylinositol 3-Kinase Complex by Ubiquitin and SUMO. (ruhr-uni-bochum.de)
However, over the same period protein kinases have rapidly become one of the most significant classes of drug targets for the pharmaceutical industry, with the global market for kinase therapies being about US$15 billion per annum in 2010 and this value is predicted to double by 2020 (3). (ddw-online.com)

Once inside the cell , the degrader must be able to engage either with the target protein to form the corresponding binary complex or with the specific E3 ligase , followed by the involvement of the third binding partner to form the ternary complex . (cisbio.jp)

We have therefore created the first BRD9-directed chemical degraders, through iterative design and testing of heterobifunctional ligands that bridge the BRD9 bromodomain and the cereblon E3 ubiquitin ligase complex. (princeton.edu)

Activation and nuclear translocation of NF-κB occurs following signal-induced phosphorylation of IκB, which leads to proteolysis via the ubiquitin pathway. (justia.com)
Targeting Proteins and Proteolysis to counter Cancer. (cisbio.jp)

Mechanistically, we show that RNF168-generated mUb-H2A recruits BARD1 through a BRCT domain ubiquitin-dependent recruitment motif (BUDR). (nih.gov)
DNA damage response-related E3 ligases, such as RNF168, FBXW7, and HERC2, were generated with more than 10% mutation in several cancer cells. (bmbreports.org)

α-Synuclein is an abundant brain protein that binds to lipid membranes and is involved in the recycling of presynaptic vesicles. (ox.ac.uk)
The resulting N-terminal Arg (Nt-Arg) binds the ZZ domain of SQSTM1, inducing oligomerization of SQSTM1-TRIM13 complexes and facilitating recruitment of LC3 on phagophores to the sites of reticulophagy. (nih.gov)
To deplete a protein using Trim-Away, researchers can simply choose an antibody that binds to their protein of interest and deliver this antibody to cells by giving them a mild electric shock. (cam.ac.uk)
Once inside cells the antibody binds its protein target, forming a protein-antibody complex that is recognised by TRIM21 and destroyed within minutes. (cam.ac.uk)
The Origin Recognition Complex (ORC) binds to sites in chromosomes to specify the location of origins of DNA replication. (imperial.ac.uk)

Mechanisms by which E. chaffeensis establishes intracellular infection, and avoids host defenses are not well understood, but involve functionally relevant host-pathogen interactions associated with tandem and ankyrin repeat effector proteins. (frontiersin.org)
Both own phosphorylation status and direct protein-protein interactions are increasingly investigated [ 5 ]. (biomedcentral.com)
Fusion Proteins offer an important biological assay for direct protein-to-protein interactions. (thermofisher.com)
Current projects are focused on CA and capsid interactions, proteins involved in trafficking and nuclear import, retroviral intasome structure, and analyses of the HIV-1 pre-integration complex. (pitt.edu)
The GTPase-activating protein p190RhoGAP reduced RhoA activity through increased physical interactions between the two proteins. (cytoskeleton.com)

ARAP2 associates with adaptor protein with PH domain, PTB domain and leucine zipper motifs 1 (APPL1) in endosomes (Chen et al. (bio2009.org)

WD-repeat proteins are a large family found in all eukaryotes and are implicated in a variety of functions ranging from signal transduction and transcription regulation to cell cycle control and apoptosis. (embl.de)
Members of this family include the signal-transducing G protein beta subunit, as well as other proteins that regulate signal transduction, transcription, pre-mRNA splicing, cytoskeletal organization, and vesicular fusion. (embl.de)
A variety of extracellular stimuli including mitogens, cytokines, antigens, stress inducing agents, UV light and viral proteins initiate a signal transduction pathway that ultimately leads to NF-κB release and activation. (justia.com)
The Ubl SUMO regulates a growing number of recognized proteins involved in the cell cycle, DNA repair, the stress response, nuclear transport, transcription, and signal transduction. (enzolifesciences.com)

Phosphorylation of the receptor protein Pex5p modulates import of proteins into peroxisomes. (ruhr-uni-bochum.de)
L ike protein phosphorylation by kinases, protein ubiquitylation regulates many aspects of cell function and provides a wealth of drug target opportunities across many therapeutic areas including cancer, cardiovascular, metabolism, inflammation, neurodegeneration and infectious diseases. (ddw-online.com)

Trim-Away ubiquitinates and degrades lysine-less and N-terminally acetylated substrates. (cam.ac.uk)

Finally, we showed that Bonus SUMOylation is mediated by the SUMO E3-ligase Su(var)2-10, revealing that although SUMOylation of TIF1 proteins is conserved between insects and mammals, both the mechanism and specific site of modification is different in the two taxa. (elifesciences.org)
It has been demonstrated that the target lysine of RanGAP1, as well as the C-terminus of mature SUMO-1, lie within mobile regions of the two proteins. (enzolifesciences.com)
Effects of Nephrolithiasis on Serum DNase (Deoxyribonuclease I and II) Activity and E3 SUMO-Protein Ligase NSE2 (NSMCE2) in Malaysian Individuals. (nih.gov)

The Pleiner lab combines mechanistic cell biology, structural biochemistry and protein engineering to dissect the pathways and molecular machines that mature human membrane proteins to a fully functional state. (stanford.edu)

We also develop alpaca-derived and synthetic nanobodies as tools to modulate intracellular pathways that globally regulate protein homeostasis in health and disease. (stanford.edu)
For example, NEDD8 activates SCF and related ubiquitin ligases, ISG15/UCRP is induced during in the antiviral interferon response, Apg12p and Apg8p regulate the autophagy pathway, and Hub1p modifies cell polarity factors. (enzolifesciences.com)
Recently, the potential for the actin cytoskeleton (e.g., actin-binding protein complex Arp2/3) to regulate the activity and protein expression of upstream Rho-family GTPases (e.g. (cytoskeleton.com)

Here we have determined the 2.2 A crystal structure of an intermediate of UbcH5b~ubiquitin (Ub) conjugate, which is assembled into an infinite spiral through the backside interaction. (rcsb.org)

A nanobody-based strategy for rapid and scalable purification of human protein complexes. (stanford.edu)
Here, we present a streamlined workflow for the rapid production of proteins or protein complexes using lentiviral transduction of human suspension cells, combined with highly specific nanobody-mediated purification and proteolytic elution. (stanford.edu)

The addition of a single ubiquitin unit to PTEN seems to promote a nuclear localization for PTEN. (rupress.org)
SUMO1 is involved, for instance, in targeting RANGAP1 to the nuclear pore complex protein RANBP2. (thermofisher.com)
Scmh1 encodes a protein with quite a few characteristic domains, including the malignant brain tumor domains, the professional line, glutamine, serine, and threonine rich domains, the N terminal and C terminal putative nuclear localization sig nals, as well as Scm polyhomeotic l mbt domain, also designated as the SAM domain. (gabasignaling.com)
Scmh1 encodes a protein with many characteristic domains, as well as the malignant brain tumor domains, the pro line, glutamine, serine, and threonine wealthy domains, the N terminal and C terminal putative nuclear localization sig nals, plus the Scm polyhomeotic l mbt domain, also designated since the SAM domain. (gabasignaling.com)
During interphase, RanGAP1 is bound to the cytoplasmic side of the nuclear pore complex via a sumoylationdependent interaction with the IR domain of the large nucleoporin RanBP2/Nup358. (enzolifesciences.com)

FBXL11 is a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. (thermofisher.cn)
We chose proteins that include amino and carboxyl extensions as well as proteins that are made up entirely of WD-repeats. (embl.de)
Ubiquitin (Ub) is a highly conserved 76 amino-acid protein found throughout eukaryotic cells. (ubiquigent.com)

The proteostasis network (PN) is an assembly of distinct dynamic molecular pathways that control the functionality of the proteome (proteome homeodynamics) during protein synthesis, folding, trafficking, and degradation. (hindawi.com)
However, recruitment can happen in dependently of trimethylated H3K27 by means of molecular focusing on of RYBP PcG complex 1. (gabasignaling.com)

However, the component(s) of the ubiquitin system mediating IκB recognition have not been identified. (justia.com)
Despite the development of chemical probes targeting the BRD9 bromodomain, there is a limited understanding of BRD9 function beyond acetyl-lysine recognition. (princeton.edu)

Modulating agents include human E3 ubiquitin ligases, antibodies thereto and variants thereof, as well as related proteins. (justia.com)

Rqc2p stabilizes Ltn1p on the 60S and recruits charged tRNAs to the 60S to catalyze elongation of the nascent protein with carboxy-terminal alanine and threonine extensions (CAT tails). (escholarship.org)

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. (embl-heidelberg.de)
The cryo-EM structure of the trapped RNF213:E2∼Ub intermediate reveals RNF213 C-terminal domain as the E2 docking site, which positions the ubiquitin-loaded E2 proximal to the catalytic zinc finger, facilitating nucleophilic attack of Cys4462 on the E2∼Ub thioester. (biorxiv.org)

Catalysis of the reaction: ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine. (systemsbiology.net)
We provide evidence for potential influences of E3 ligase and poly adenosine diphosphate (ADP-ribose) polymerase 1 (PARP1) activity on neurodegenerative pathology. (frontiersin.org)

In contrast, as seen with many proteins, the addition of multiple linked ubiquitin units targets PTEN for destruction. (rupress.org)
By analogy with the concept of the 'druggable genome', the question arises as to which potential drug targets might PROTAC-mediated protein degradation be most applicable. (tissueandcells.com)
Here, they present a systematic approach to the assessment of the PROTAC tractability (PROTACtability) of protein targets using a series of criteria based on data and information from a diverse range of relevant publicly available resources. (tissueandcells.com)
Using our approach, they identified 1,067 proteins of the human proteome that have not yet been described in the literature as PROTAC targets that offer potential opportunities for future PROTAC-based efforts. (tissueandcells.com)
Each heterobifunctional PROTAC molecule targets a protein of interest (POI), serving as a bridge to bring it into close proximity with an E3 ligase. (cisbio.jp)

The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. (thermofisher.cn)
The RING domain is a protein interaction domain that has been implicated in a range of diverse biological processes. (embl-heidelberg.de)

SCF Pop1p-Pop2p mediated Rum1p ubiquitylation in vitro ( 2A ) Various Cdc2p complexes were affinity purified from cells co-expressing 6 × His-Myc-tagged Cdc2p and HA-tagged cyclins on nickel NTA resin. (biomedcentral.com)
6 × His-Myc-tagged Pop2p and HA-Pop1p were co-overexpressed in wild-type fission yeast, and Pop1p-Pop2p complexes were affinity-purified on Ni-NTA resin. (biomedcentral.com)
The bottom panel shows the affinity-purified Pop1p and Pop2p complexes used in the binding assay. (biomedcentral.com)
This GST-fusion protein can then be purified from cells via its high affinity for glutathione. (thermofisher.com)

Hershko, A. & Ciechanover, A. The ubiquitin system. (nature.com)
It is not known whether all WD-repeat proteins are unable to fold when synthesized in an in vitro system. (embl.de)
Is novel chemistry the final frontier for ubiquitin system drug discovery? (ddw-online.com)
Although the widespread use of target-focused libraries has led to the rapid expansion of novel chemistry as research tools in drug discovery to exploit many classes of drug target, the ubiquitin system still remains a largely untapped medicinal chemistry opportunity. (ddw-online.com)
In this article, we propose that chemical libraries which target the ubiquitin system are the missing keys to unlock the therapeutic potential of ubiquitin system drug discovery. (ddw-online.com)
Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. (cusabio.com)

The family of WD-repeat proteins comprises over 30 different proteins that share a highly conserved repeating motif [Neer, E. J., Schmidt, C. J., Nambudripad, R., & Smith, T. F. (1994) Nature 371, 297-300]. (embl.de)

However, the finding by two independent research groups that mice expressing mutant PTEN proteins that selectively lack lipid phosphatase activity develop worse tumors than mice expressing no PTEN argues strongly against PTEN having dominant tumor suppressor functions that act fully independently of its PIP 3 phosphatase activity. (rupress.org)

SUMO1 is an ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer. (thermofisher.com)
2010). Thus, ubiquitin can be attached to a substrate either as a monomer or as a poly-ubiquitin chain. (ubiquigent.com)

https://doi.org/10.1083/jcb.201604025 ) show that Importin-11 traffics the tumor suppressor PTEN into the nucleus and in so doing protects it from cytoplasmic proteins that cause PTEN degradation. (rupress.org)

SHARPIN forms a linear ubiquitin ligase complex regulating NF-B activity and apoptosis. (nature.com)
SHARPIN is a component of the NF-B-activating linear ubiquitin chain assembly complex. (nature.com)

This protein is a transcription factor regulating the expression of some detoxification and antioxidant enzymes. (wikipedia.org)

In the cell, RNF213 was shown to be involved in fatty acid metabolism ( 11 ), and to associate with intracellular lipid droplets in a manner dependent on its E3 ligase and ATPase activities ( 12 ). (biorxiv.org)

If WD proteins form structures similar to G beta, their hydrodynamic properties should be those of compact, globular proteins, and they should be resistant to cleavage by trypsin. (embl.de)
Our working definition of folding was that the proteins from globular, trypsin-resistant structures because, except for G beta gamma, their functions are not known or cannot be assayed in reticulocyte lysates. (embl.de)
2009). Reflecting these different structures alternative ubiquitin chain types can display varying specificities for ubiquitin binding domains. (ubiquigent.com)

Therefore, dynamic neddylation and deneddylation of cullin is important for regulation of CRL complex activity. (wikipedia.org)

TRIM/RBCC is an ancient protein family characterized by the presence of an N-terminal RING finger domain closely followed by one or two B-boxes and a coiled coil domain. (elifesciences.org)
This domain is found in proteins involved in a variety of processes. (systemsbiology.net)
Taxonomic distribution of proteins containing WD40 domain. (embl.de)
The complete taxonomic breakdown of all proteins with WD40 domain is also avaliable . (embl.de)
Click on the protein counts, or double click on taxonomic names to display all proteins containing WD40 domain in the selected taxonomic class. (embl.de)
We developed small molecule ligands to the SQSTM1 ZZ domain and demonstrate that these chemical mimics of Nt-Arg facilitate reticulophagy and autophagic protein quality control of misfolded aggregates in the ER. (nih.gov)

WNK1 is an assembly factor for the human ER membrane protein complex. (stanford.edu)

Anatomy8

Organisms5

Diseases2

Chemicals and Drugs81

Analytical, Diagnostic and Therapeutic Techniques and Equipment14

Phenomena and Processes40

Information Science3

Health Care1

Ubiquitination20

Residues7

Signaling pathway1

Covalent5

Enzyme7

Mediates4

Residue4

Attachment1

Proteasome11

Proteasomal degradation5

Subunits6

Genes6

Target proteins2

Cellular15

Substrate proteins2

Cell's protein degradation machinery1

Linear ubiquitin chains2

Molecules2

Abstract1

Histone1

Specificity6

Homologous2

Transmembrane1

Chromatin1

Gene5

Chains6

Kinase2

Ternary complex1

Cereblon1

Proteolysis2

RNF1682

Binds5

Interactions5

Adaptor1

Signal transduction4

Phosphorylation2

Substrates1

SUMO3

Biochemistry1

Regulate3

Conjugate1

Purification2

Nuclear5

Amino3

Molecular2

Recognition2

Antibodies1

Threonine1

Zinc2

Diphosphate2

Targets5

Interaction2

Affinity4

System6

Highly conserved1

Mice1

Monomer2

Cytoplasmic1

SHARPIN2

Transcription factor1

Lipid1

Structures3

Regulation1

Domain6

WNK11