Disease relevance of MGC127041

• Ribosomal S27a coding sequences upstream of ubiquitin coding sequences in the genome of a pestivirus [1].
• Chronic metabolic acidosis increases mRNA levels for components of the ubiquitin-mediated proteolytic pathway in skeletal muscle of dairy cows [2].
• Digestion of uH2B with Staphylococcus aureus V8 protease yielded the peptide 114-125 containing the ubiquitin moiety [3].
• Small ubiquitin-related modifier-1 modification mediates resolution of CREB-dependent responses to hypoxia [4].
• Extracellular ubiquitin inhibits the TNF-alpha response to endotoxin in peripheral blood mononuclear cells and regulates endotoxin hyporesponsiveness in critical illness [5].

Psychiatry related information on MGC127041

• Like rates of proteolysis, the amount of Ub-protein conjugates and the fraction of Ub conjugated to proteins increased progressively during food deprivation and returned to normal within 1 day of refeeding [6].
• The discovery that ubiquitin is associated with the neurofibrillary tangles of Alzheimer's disease and inclusion bodies of other neurodegenerative disorders raises the possibility that ubiquitin is playing a role in the pathology [7].

High impact information on MGC127041

• Ubiquitin-conjugating enzyme variant (UEV) proteins resemble ubiquitin-conjugating enzymes (E2s) but lack the defining E2 active-site residue [8].
• These findings support a model in which an Mms2p/Ubc13p complex assembles novel polyubiquitin chains for signaling in DNA repair, and they suggest that UEV proteins may act to increase diversity and selectivity in ubiquitin conjugation [8].
• Ubiquitin tag for sperm mitochondria [9].
• In eukaryotes, ubiquitin (Ub)-dependent proteolysis is essential for bulk protein turnover as well as diverse processes including cell-cycle control, differentiation, antigen presentation, and the stress response [10].
• Molecular conservation of 74 amino acid sequence of ubiquitin between cattle and man [11].

Chemical compound and disease context of MGC127041

• To provide a fluorescence probe for equilibrium and kinetic folding studies on ubiquitin, cassette mutagenesis in an Escherichia coli expression plasmid was used to replace the largely buried Phe 45 by a tryptophan [12].
• Fragile gangliosides with several sialic acid residues are desorbed under high pressure and remain intact without the typical losses of sialic acid, and a protein standard, ubiquitin (8565.64 Da), is desorbed with minimal dehydration [13].

Biological context of MGC127041

• Sequence comparisons strongly suggest that the S27a and the ubiquitin coding sequences found in the genome of CP Rit were both derived from a bovine mRNA encoding a hybrid protein with the structure NH2-ubiquitin-S27a-COOH [1].
• The complete amino acid sequence of ubiquitin, an adenylate cyclase stimulating polypeptide probably universal in living cells [14].
• Characterization of a full-length cDNA encoding a bovine four tandem-repeat ubiquitin [15].
• Screening of a bovine seminal vesicle cDNA library in lambda gt11 with monospecific anti-ubiquitin IgGs yielded two independent clones pUF4AA and pUD4AA [15].
• Our laboratory previously demonstrated the activation of ubiquitin conjugation during spermatogenesis [16].

Anatomical context of MGC127041

• The biosynthesis of ubiquitin by parathyroid gland [17].
• It is a monomeric Ub-binding protein abundant in erythrocytes and reticulocytes [18].
• A brief exposure of lens epithelial cells to physiologically relevant levels of H2O2 induces a transient increase in activity of the ubiquitin-dependent pathway [19].
• Ubiquitinylation and ubiquitin-dependent proteolysis in vertebrate photoreceptors (rod outer segments). Evidence for ubiquitinylation of Gt and rhodopsin [20].
• Considered together, the data support a novel role for the ubiquitin-dependent pathway in the regulation of mammalian phototransduction protein levels and/or activities and provide the first identification of a non-calpain proteolytic system in photoreceptors [20].

Associations of MGC127041 with chemical compounds

• Nor have assembly mechanisms or definitive functions been assigned to polyubiquitin chains linked through several other lysine residues of ubiquitin [21].
• We observed a replacement of serine (133) by phenylalanine in the second ubiquitin repeat [15].
• Iodination of tyrosine 59 of ubiquitin selectively blocks ubiquitin's acceptor activity in diubiquitin synthesis catalyzed by E2(25K) [22].
• The activity of the isopeptidase is inhibited by iodoacetamide and Ub aldehyde [18].
• One of these chain members (Ubq2) was purified from wheat and was demonstrated via amino acid sequence analysis of tryptic fragments to consist of two ubiquitin monomers joined via a glycine 76-->lysine 48 linkage [23].

Physical interactions of MGC127041

• Recent studies have shown that selection of proteins for degradation by the ubiquitin system occurs most probably by binding to specific sites of the ubiquitin-protein ligase, E3 [24].
• We previously showed that the bovine papillomavirus E1 protein is unstable and becomes resistant to ubiquitin-mediated degradation when tightly bound to cyclin E-cyclin-dependent kinase 2 (Cdk2) before the start of DNA synthesis [25].

Enzymatic interactions of MGC127041

• Ubiquitin carrier protein-catalyzed ubiquitin transfer to histones. Mechanism and specificity [26].
• The mammalian ubiquitin conjugating enzyme known as E2-25K catalyzes the synthesis of polyubiquitin chains linked exclusively through K48-G76 isopeptide bonds [27].
• The substrate specificity of the ubiquitin (Ub) conjugation system was explored with regard to recognition of unfolded conformation and/or oxidized methionine residues in six derivatives of bovine RNase A [28].

Regulatory relationships of MGC127041

• Multiple forms of ubiquitin-protein ligase. Binding of activated ubiquitin to protein substrates [29].
• Isolation and sequence of an interferon-tau-inducible, pregnancy- and bovine interferon-stimulated gene product 15 (ISG15)-specific, bovine ubiquitin-activating E1-like (UBE1L) enzyme [30].
• Addition of tRNA to the ribonuclease inhibited system (following inhibition of the ribonuclease) restored both the conjugation activity and the ubiquitin- and ATP-dependent degradation of these substrates [31].
• Depletion of endogenous ubiquitin from the reticulocyte lysate with purified antibodies against this polypeptide inhibits the insertion of monoamine oxidase B, and this inhibition is relieved if ubiquitin is restored [32].

Other interactions of MGC127041

• This reaction can be reconstituted using the ubiquitin-conjugating enzyme (E2) known as UbcH5A, a 120-kDa protein(s) that behaves as a ubiquitin-protein ligase (E3), and ubiquitin-activating enzyme (E1) [21].
• Experimental conditions were established under which a fusion protein containing an amino-terminal fragment of cyclin B is ligated to ubiquitin only in extracts from M-phase but not from interphase cells [33].
• Components of a system that ligates cyclin to ubiquitin and their regulation by the protein kinase cdc2 [33].
• For each of the subgenomes, a large internal deletion was found together with an inserted sequence encoding part of ribosomal protein S27a fused to an N-terminally truncated ubiquitin monomer [34].
• Indeed, a novel enzyme, E3Histone, which could conjugate ubiquitin to histones H1, H2A, H2B, H3, and H4 in vitro, was found [16].

Analytical, diagnostic and therapeutic context of MGC127041

• The properties of these enzymes suggest that there may be distinct pathways for ubiquitin-ubiquitin ligation versus substrate-ubiquitin ligation in vivo [21].
• Tryptic digestion of maleated ubiquitin yielded four peptide fragments that were resolved by molecular sieve chromatography and coded in order of decreasing chain length (MT-1, MT-2, MT-3, and MT-4) [14].
• Using the 20-kDa ubiquitin-conjugating enzyme TaUBC7 from wheat, we have generated free, glycine 76-->lysine 48-linked multiubiquitin chains (Ubqn), and have individually purified Ubqn species (n < or = 6) by anion-exchange, high pressure liquid chromatography [23].
• Tryptic digestion of intact Ub2 gave products consistent with the existence of an isopeptide linkage between the COOH terminus of one Ub and Lys-48 of the other; this structure was confirmed by sequence analysis of the unique Ub2 tryptic fragment [35].
• Immunofluorescence microscopy was used to study the intracellular localization of ubiquitin [36].

References