LigasesProteinsEnzymesProteasome systemDegradationEnzymePathwayRegulatesGeneConjugationLigase activitySpecific peptidaseMotifCellularUbiquitinationPathwaysTranscriptionalSubstratesProtein-protein intComplexProtein's functionCatalytic domainRING E3BRCA1PathogenesisMoleculeBindStructuresCysteineRegulationSkp1RAP80MediatesCullinComplexesReplicationMolecularMutationsFactorChainsViralDomains
Ligases15
- Cullin RING E3 ubiquitin ligases (CRLs) function in the ubiquitin proteasome system by catalysing the transfer of ubiquitin from E2 conjugating enzymes to specific substrate proteins. (dundee.ac.uk)
- This complex presents direct structural evidence of the recruitment of a human ubiquitin ligase by a viral BC box protein that mimics the conserved interactions of cellular ubiquitin ligases. (nih.gov)
- 1. TRIM E3 Ubiquitin Ligases in Rare Genetic Disorders. (nih.gov)
- RING domain self-association and activity in TRIM E3 ubiquitin ligases. (nih.gov)
- 8. TRIM proteins as RING finger E3 ubiquitin ligases. (nih.gov)
- 16. TRIM/RBCC, a novel class of 'single protein RING finger' E3 ubiquitin ligases. (nih.gov)
- In fact, F-box proteins are one of the four subunits of ubiquitin protein ligases, called SCFs. (nih.gov)
- SCF ligases bring ubiquitin conjugating enzymes to substrates that are specifically recruited by the different F-box proteins. (nih.gov)
- The C-terminus of each subunit (α, β, and γ) contains a PPXY motif for interaction with the WW domains of the ubiquitin-protein ligases, Nedd4 and Nedd4-2. (tcdb.org)
- Subcellular localization and ubiquitin-conjugating enzyme (E2) interactions of mammalian HECT family ubiquitin protein ligases. (embl.de)
- In most instances, the transfer of ubiquitin to target proteins is catalyzed by the action of ubiquitin protein ligases (E3s). (embl.de)
- The goal of the Oliver Lab is to identify ubiquitin ligases and then use genetic, cellular, and biochemical approaches to define how those enzymes regulate immune cell function. (chop.edu)
- Some of the lab's efforts have focused on catalytic ubiquitin ligases of the Nedd4-family. (chop.edu)
- The Oliver Lab's recent work has employed systems biology approaches in which it has integrated transcriptome, proteome, and ubiquitome information to identify Cullin E3 ubiquitin ligases that are particularly active as T cells transition from resting to activated states. (chop.edu)
- The lab is now poised to define how cullin ligases form distinct ubiquitin complexes in T cells or other immune cells and the unique set of substrates targeted by these complexes. (chop.edu)
Proteins19
- E2 enzymes catalyze attachment of ubiquitin and ubiquitin-like proteins to lysine residues directly or through E3-mediated reactions. (rcsb.org)
- These wide ranging consequences of the loss of BRCA1 function are explained by the proteins numerous interactions with several molecules, including the products of tumor suppressor genes and cancer-causing genes or oncogenes. (news-medical.net)
- PINK1 and LRRK2), modulators of the activity of the ubiquitin-protein ligase, Parkin, proteostasis agents to block α-synuclein filament assembly and toxicity, or promote the refolding of mutant proteins, modulators of α-synuclein transfer between cells, reagents to regulate cargo dynamics along axonal microtubule networks, stimulators of autophagy and/or modulators of cellular stress pathways. (medscape.com)
- This protein functions as a deubiquitinase, which means it removes a molecule called ubiquitin from certain proteins. (medlineplus.gov)
- The presence of ubiquitin molecules on a protein can affect the activity of the protein and its interactions with other proteins. (medlineplus.gov)
- By removing ubiquitin, BAP1 helps regulate the function of many proteins involved in diverse cellular processes. (medlineplus.gov)
- Reduction or loss of this protein's function likely prevents the removal of ubiquitin molecules from certain proteins. (medlineplus.gov)
- This protein catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation. (biolegend.com)
- The efficiency of different salts to screen charge interactions in proteins: a Hofmeister effect? (google.de)
- 20. Functional interactions between ubiquitin E2 enzymes and TRIM proteins. (nih.gov)
- Some F-box proteins have been shown to be critical for the ubiquitin-mediated degradation of cellular regulatory proteins. (nih.gov)
- Peli1 regulates the activation of a metabolic kinase, mTORC1, through its interaction with mTORC1 inhibitory proteins TSC1 and TSC2. (medscape.com)
- Find Ubiquitin Specific Peptidase 12 Proteins with a specific Grade. (antibodies-online.com)
- Find Ubiquitin Specific Peptidase 12 Proteins for a variety of species such as anti-Human Ubiquitin Specific Peptidase 12, anti-Atlantic Salmon Ubiquitin Specific Peptidase 12, anti-Cow Ubiquitin Specific Peptidase 12. (antibodies-online.com)
- Find Ubiquitin Specific Peptidase 12 Proteins validated for a specific application such as ELISA, WB, AP, AA. (antibodies-online.com)
- Ubiquitin-conjugating enzymes are a family of related proteins that participate in the ubiquitination of proteins. (embl.de)
- As ubiquitin-conjugating enzymes interact with different substrates or other accessory proteins in the ubiquitination pathway, these variable surface regions may confer distinct specificity to individual enzymes. (embl.de)
- Different enhancer classes in Drosophila bind distinct architectural proteins and mediate unique chromatin interactions and 3D architecture. (nih.gov)
- Tagging" a protein with ubiquitin can improve interactions between proteins to promote signaling or initiate protein degradation. (chop.edu)
Enzymes3
- One of the most interesting aspects of these enzymes is the ability of some members to selectively recognize specific linkage types between ubiquitin in polyubiquitin chains and their endo and exo specificity. (rcsb.org)
- Deubiquitinating enzymes (DUBs) regulate numerous cellular functions by removing ubiquitin modifications. (nature.com)
- A novel polyubiquitin chain linkage formed by viral Ubiquitin is resistant to host deubiquitinating enzymes. (ncbs.res.in)
Proteasome system3
- This project aims to study the human ubiquitin proteasome system (UPS) which is an important pathway for host-pathogen interactions, yet remains unexplored in human malaria, including in Kenyan children who will be the focus of the studies. (nih.gov)
- Glucocorticoids elicit the atrophy of muscle by increasing the rate of protein degradation by the ubiquitin-proteasome system and autophagy lysosome system. (frontiersin.org)
- The misregulation of Ubiquitin-Proteasome System (UPS) can result in the pathogenesis of human diseases including cancer. (nih.gov)
Degradation2
- The ubiquitin "tag" also promotes breakdown (degradation) of a protein. (medlineplus.gov)
- Evidence from our laboratory indicates that endogenous ER binds to endogenous calmodulin, attenuating the degradation of ER by sequestering it away from the ubiquitin degradation pathway. (nih.gov)
Enzyme10
- The structural data are consistent with previously reported mutational data on the mammalian enzyme, which, together with the fact that the ULD residues that bind to ubiquitin are conserved, points to a similar mechanism behind the exo specificity of the human enzyme. (rcsb.org)
- Moreover, our structures show that the unproductively oriented catalytic cysteine in the free enzyme is aligned correctly when ubiquitin binds, suggesting a mechanism for ubiquitin selectivity. (rcsb.org)
- In contrast to most ubiquitin conjugation, the SUMO E2 enzyme Ubc9 is sufficient for substrate recognition and lysine modification of known SUMO targets. (rcsb.org)
- Then, the cells were intracellularly stained with 2 µg/ml Alexa Fluor® 594 conjugated (red) E1 Ubiquitin Activating Enzyme Antibody (clone 2G2.3.5) in a blocking buffer overnight at 4°C. Actin filaments were labeled with Alexa Fluor® 488 Phalloidin (green). (biolegend.com)
- E1 Ubiquitin Activating Enzyme (UBE1) initiates the cascade of conjugation by activating their respective modifiers. (biolegend.com)
- The gene for E1 Ubiquitin activating enzyme complements an X-linked mouse temperature-sensitive defect in DNA synthesis, and thus may function in DNA repair. (biolegend.com)
- As a postdoctoral researcher working with stem cells in culture, Werner and his colleagues "stumbled across a ubiquitin-modifying enzyme that controls neural crest cell differentiation," he says. (nih.gov)
- UBE2C(Ubiquitin Conjugating Enzyme E2 C) was chosen for further validation in TCGA cohort on mRNA level and in our patient samples on protein level by immunohistochemistry. (jcancer.org)
- Crystal structure of a class I ubiquitin conjugating enzyme (Ubc7) from Saccharomyces cerevisiae at 2.9 angstroms resolution. (embl.de)
- Analysis of the 13 ubiquitin-conjugating enzyme sequences in S. cerevisiae indicates that there may be two other regions where extra residues could be inserted into the common tertiary fold. (embl.de)
Pathway3
- OTUD1 regulates the canonical NF-κB pathway by hydrolyzing K63-linked ubiquitin chains from NF-κB signaling factors, including LUBAC. (nature.com)
- Drosophila Argonaute2 turnover is regulated by the ubiquitin proteasome pathway. (nih.gov)
- It is also involved in the ubiquitin-proteasome pathway through interaction with the AU-rich element RNA-binding protein 1. (caslab.com)
Regulates3
- We showed that PBF binds to the E3 ubiquitin ligase RAD6, which also ubiquitinaties p53, and regulates its expression. (bham.ac.uk)
- The lab has discovered an E3 ubiquitin ligase that regulates cytokine signaling in T cells. (chop.edu)
- FLIM-FRET analysis of protein-protein interactions showed that PLIN5 S155 phosphorylation regulates PLIN5 interaction with adipose triglyceride lipase at the lipid droplet, but not with α-β hydrolase domain-containing 5. (uci.edu)
Gene6
- The BAP1 gene provides instructions for making a protein called ubiquitin carboxyl-terminal hydrolase BAP1 (shortened to BAP1). (medlineplus.gov)
- EXPANSION OF FOCUS PAS-03-160: GENE/ENVIRONMENT INTERACTION IN NEURODEGENERATIVE DISEASE RELEASE DATE: July 20, 2004 NOTICE: NOT-ES-04-009 National Institute of Environmental Health Sciences (NIEHS) ( http://www.niehs.nih.gov ) The National Institute of Environmental Health Sciences is announcing an expansion of focus for PAS-03-160: Gene/Environment Interaction in Neurodegenerative Disease. (nih.gov)
- The original program announcement https://grants.nih.gov/grants/guide/pa-files/PAS-03-160.html focused on gene-environment interactions in the etiology of amyotrophic lateral sclerosis (ALS). (nih.gov)
- RB and c-Myc activate expression of the E-cadherin gene in epithelial cells through interaction with transcription factor AP2. (nih.gov)
- The Baculoviridae family of viruses encode a viral Ubiquitin (vUb) gene. (ncbs.res.in)
- Moreover, the interaction of FOXM1 and SMAD3 promoted TGF-β/SMAD3-mediated transcriptional activity and target gene expression. (jci.org)
Conjugation1
Ligase activity2
- In addition to its ubiquitin ligase activity, DTX3L-PARP9 also acts as an ADP-ribosyl transferase for Gly 76 on the C-terminus of ubiquitin. (portlandpress.com)
- Cancer-associated somatic mutations of KLHL6 inhibit its ubiquitin ligase activity by disrupting the interaction with CULLIN3. (nih.gov)
Specific peptidase2
- UV-stimulated scaffold protein A (UVSSA), the product of UVSSA, which is required for stabilization of Cockayne syndrome group B (CSB) protein and reappearance of the hypophosphorylated form of RNA polymerase II after UV irradiation, forms a complex with ubiquitin-specific peptidase 7 (USP7). (nih.gov)
- The interaction of ABHD11-AS1 with SART3 promotes USP15 (ubiquitin specific peptidase 15) nuclear localization. (cdc.gov)
Motif5
- Orthologous to human UIMC1 (ubiquitin interaction motif containing 1). (nih.gov)
- Furthermore, our homology modeling reveals that the Vif Cullin box and zinc finger motif may be positioned adjacent to the N terminus of Cullin5 for interaction with loop regions in the first cullin repeat of Cullin5. (nih.gov)
- The Cell Biology Group recently described the identification of a novel protein, referred to as receptor-associated protein 80 (RAP80) or ubiquitin interaction motif-containing 1 (UIMC1). (nih.gov)
- Skp1 connects cell cycle regulation to the ubiquitin proteolysis machinery through a novel motif, the F-box. (nih.gov)
- Disruption of this interaction, as in Liddle's syndrome where mutations delete or alter the PPXY motif of either the β or γ subunits, has been shown to result in increased ENaC activity and arterial hypertension. (tcdb.org)
Cellular3
- Human immunodeficiency virus (HIV) virion infectivity factor (Vif) causes the proteasome-mediated destruction of human antiviral protein APOBEC3G by tethering it to a cellular E3 ubiquitin ligase composed of ElonginB, ElonginC, Cullin5, and Rbx2. (nih.gov)
- Consequently, the parallel development of more refined protein-protein interactions maps has aided the chance of identifying those protein complexes and/or cellular pathways, which, when disrupted, lead to the development of disease. (medscape.com)
- Differential cellular responses to adhesive interactions with galectin-8 and fibronectin coated substrates. (weizmann.ac.il)
Ubiquitination2
- However, the surface properties, ubiquitination activity, and the interaction with Ubiquitin-binding domains are similar between vUb and Ub. (ncbs.res.in)
- The multisite nature of the Sic1-Cdc4 interaction confers cooperative dependence on kinase activity for Sic1 recognition and ubiquitination under equilibrium reaction conditions. (mshri.on.ca)
Pathways4
- o Interaction of environmental agents with ubiquitin/proteasomal pathways and pathologies. (nih.gov)
- The National Heart, Lung, and Blood Institute invites research grant applications to delineate the protein interactions and pathways governing membrane trafficking pathways operative in pulmonary health and disease and develop novel therapeutic interventions. (nih.gov)
- Building on the newer pathways for pathogenesis includes the E3 ubiquitin ligase Peli1 as an important regulator of T-cell metabolism and antitumor immunity. (medscape.com)
- These findings elaborate on the regulation of mTORC1 during energetic stress and interactions between prosurvival and prodeath pathways. (medscape.com)
Transcriptional2
- FOXM1 prevented the E3 ubiquitin-protein ligase transcriptional intermediary factor 1 γ (TIF1γ) from binding SMAD3 and monoubiquitinating SMAD4, which stabilized the SMAD3/SMAD4 complex. (jci.org)
- We subsequently documented that an interaction between calmodulin and ER in the nucleus is required for estrogen-stimulated ER transcriptional activation. (nih.gov)
Substrates1
- NAD + -dependent ADP-ribosylation of ubiquitin by DTX3L-PARP9 prevents ubiquitin from conjugating to protein substrates. (portlandpress.com)
Protein-protein int1
- Simulation results show that the hydrophobic protein-protein interaction (or recognition) that is essential to biological functions can be interrupted by a graphene nanosheet. (ibm.com)
Complex4
- Herein we report the crystal structure of two constructs of UCH37 from Trichinella spiralis in complex with a ubiquitin-based suicide inhibitor, ubiquitin vinyl methyl ester (UbVME). (rcsb.org)
- We examined the effects of 88 human DUBs on linear ubiquitin chain assembly complex (LUBAC)-induced NF-κB activation, and identified OTUD1 as a potent suppressor. (nature.com)
- Proteolysis Targeting Chimaeras (PROTAC) are hetero-bifunctional molecules which incorporate a known binding moiety to the protein of interest (POI, e.g. an inhibitor), coupled to a ligand for an E3 ubiquitin ligase complex. (le.ac.uk)
- All cell migrations happen in the ECM, and are controlled and implemented by the complex interactions between the cells and the ECM. (uncommondescent.com)
Protein's function1
Catalytic domain1
- An inspection of 39 DUB-ubiquitin structures in the Protein Data Bank reveals the uniqueness of the salt bridge in ubiquitin bound to UCH37, an interaction that disappears when the ULD is deleted, as revealed in the structure of the catalytic domain alone bound to UbVME. (rcsb.org)
BRCA12
- Retrieved on December 10, 2023 from https://www.news-medical.net/health/BRCA1-Interactions.aspx. (news-medical.net)
- Rabl J. BRCA1-A and BRISC: Multifunctional Molecular Machines for Ubiquitin Signaling. (wikipedia.org)
Pathogenesis1
Bind1
Structures2
- These structures show that the ULD makes direct contact with ubiquitin stabilizing a highly unusual intramolecular salt bridge between Lys48 and Glu51 of ubiquitin, an interaction that would be favored only with the distal ubiquitin but not with the internal ones in a Lys48-linked polyubiquitin chain. (rcsb.org)
- The cell structures that mediate those interactions between the cells and their ECM are one of the most amazing examples of functional complexity in the cell. (uncommondescent.com)
Cysteine1
- The ubiquitin-accepting cysteine is located in a cleft between two loops. (embl.de)
Regulation1
- Yes, like the spliceosome, the ubiquitin system and the transcription regulation networks, that we have considered previously. (uncommondescent.com)
Skp11
- The ubiquitin ligase SCF(Cdc4) (Skp1/Cul1/F-box protein) recognizes its substrate, the cyclin-dependent kinase inhibitor Sic1, in a multisite phosphorylation-dependent manner. (mshri.on.ca)
Mediates1
- We show the DTX3L D3 domain (230-510) mediates the interaction with PARP9 with nanomolar affinity and an apparent 1 : 1 stoichiometry. (portlandpress.com)
Cullin2
Complexes1
- RanGTP dissociates Nup153-import receptor complexes, but is required for Nup153-export receptor interactions. (embl.de)
Replication3
- Interaction between replication protein A and p53 is disrupted after UV damage in a DNA repair-dependent manner. (nih.gov)
- Single-stranded-DNA binding alters human replication protein A structure and facilitates interaction with DNA-dependent protein kinase. (nih.gov)
- Role of protein-protein interactions in the function of replication protein A (RPA): RPA modulates the activity of DNA polymerase alpha by multiple mechanisms. (nih.gov)
Molecular4
- We applied a set of complementary computational modeling methods, including docking and molecular dynamics simulations with both explicit and implicit solvent, to illustrate the impact of hydroxylated fullerenes on the structure and dynamics of ubiquitin. (nih.gov)
- Our laboratory develops and uses genetic and genomic approaches to study host-malaria parasite interaction and molecular mechanisms of the interaction using the rodent malaria parasite Plasmodium yoelii as a model. (nih.gov)
- These annotations have been derived from physical molecular interaction evidence extracted from the literature and cross-referenced in the entry, or by curator inference from information on homologs in closely related species or by inference from scientific background. (yeastgenome.org)
- Despite the significant progress, much more remains to be explored in the field of ubiquitin and molecular mechanisms of tumorigenesis. (nih.gov)
Mutations1
- The thermodynamic signature of the interaction between Cul2 and pVHL-EloBC (VBC) was determined as well as mutations that contribute toward a selectivity switch for Cul2 versus Cul5 recognition. (dundee.ac.uk)
Factor1
- We found that FOXM1/SMAD3 interaction was required for TGF-β-induced breast cancer invasion, which was the result of SMAD3/SMAD4-dependent upregulation of the transcription factor SLUG. (jci.org)
Chains1
- Upon stimulation by proinflammatory cytokines, such as TNF-α, LUBAC is recruited to the TNF receptor (TNFR), and conjugates M1-ubiquitin chains to NF-κB-essential modulator (NEMO) and receptor-interacting serine/threonine-protein kinase 1 (RIP1). (nature.com)
Viral1
- Though the vUb is homologous to the host eukaryotic Ubiquitin (Ub), its preservation in the viral genome indicates unique functions that are not compensated by the host Ub. (ncbs.res.in)