Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have characterized a second T. brucei polyubiquitin gene (UbB) that is highly similar in the coding and flanking regions to a previously described T. brucei polyubiquitin gene (UbA). However, UbB differs from UbA in 2 respects: (1) the predicted carboxy-terminal amino acid of UbB is methionine, as opposed to leucine in UbA, and (2) UbB contains approximately 13 ubiquitin repeats, as opposed to approximately 30 repeats in UbA. In Southern blots of intact T. brucei DNA separated by pulsed field gel electrophoresis, the polyubiquitin sequences have been shown to reside on band 19, which may contain 3 chromosomes. Three experiments that target a neomycin-resistance gene to the polyubiquitin locus demonstrate a one-to-one ratio of polyubiquitin 3-flanking sequences, which suggests that UbA and UbB are alleles rather than duplications. Four additional strains of T. brucei and one strain of T. equiperdum show variation in their polyubiquitin gene size, suggesting that this is a common polymorphism.
 ...
PMID:Allelic polymorphism of the Trypanosoma brucei polyubiquitin gene. 133 86

Ubiquitin has been found to be soluble in ethylene glycol and alcohols as the perchlorate or hydrochloride salt. When the effect of alcohol on the structure of ubiquitin is examined, two reversible conformational transitions are observed. Upon lowering the dielectric constant of aqueous alcohol solutions of ubiquitin from 80 to 45, the native structure of ubiquitin is converted to a form consistent with 50% helical structure. This conformational change results in a change in exposure to solvent of the single methionine and the single tyrosine residues of ubiquitin. In agreement with crystallographic results, these residues are buried in the native conformation but become fully exposed to solvent upon undergoing this transition. Further lowering of the dielectric constant to 20 results in the accumulation of a conformation with almost complete helical structure. Thus, hydrophobic interactions cause facile conformational changes in the ubiquitin structure. These results are discussed in terms of a preferential solvation model. It is shown that the results obtained with different alcohols can be normalized by the use of a dielectric constant scale. This normalization corrects for the different molar volumes of different alcohols, allows comparison of results obtained with different alcohols, and should be useful in studying this phenomenon with different proteins.
 ...
PMID:Alcohol-induced conformational changes of ubiquitin. 302 49

Ubiquitin, a 76-residue protein, occurs in cells either free or covalently joined to a variety of protein species, from chromosomal histones to cytoplasmic proteins. Conjugation of ubiquitin to proteolytic substrates is essential for the selective degradation of intracellular proteins in higher eukaryotes. We show here that a protein homologous to human ubiquitin exists in the yeast Saccharomyces cerevisiae, and that yeast extracts conjugate human ubiquitin to a variety of endogenous proteins in an ATP-dependent reaction. We have isolated the S. cerevisiae ubiquitin gene and found it to contain six consecutive ubiquitin-coding repeats in a found it to contain six consecutive ubiquitin-coding repeats in a head-to-tail arrangement. This apparently unique gene organization suggests that yeast ubiquitin is generated by processing of a precursor protein in which several exact repeats of the ubiquitin amino acid sequence are joined directly via Gly-Met peptide bonds between the last and first residues of mature ubiquitin, respectively. Ubiquitin-coding yeast DNA repeats are restricted to a single genomic locus; although the sequenced repeats differ in up to 27 of 228 bases per repeat, they encode identical amino acid sequences. As this predicted amino acid sequence differs in only 3 of 76 residues from that of ubiquitin in higher eukaryotes, ubiquitin is apparently the most conserved of known proteins.
 ...
PMID:The yeast ubiquitin gene: head-to-tail repeats encoding a polyubiquitin precursor protein. 609 20

We showed previously that the abundance of serum albumin mRNA is decreased in H4-II-E rat hepatoma cells limited for a single essential amino acid (phenylalanine, methionine, leucine, or tryptophan). To define the specificity of this phenomenon, we examined the effect of amino acid limitation on the abundance of mRNAs for 19 genes in the H4-II-E cells. These genes included six genes whose expression is either completely liver-specific or highly enriched in the liver compared with other tissues [albumin, transthyretin (TTR), transferrin, carbamyl phosphate synthetase-I, urate oxidase, class I alcohol dehydrogenase], as well as a number of ubiquitously expressed "housekeeping" genes. The results indicated that the 19 genes could be divided into three classes based on their response to amino acid limitation. Class I genes (the six liver-specific genes and alpha-tubulin) exhibit decreased expression in response to amino acid limitation. The expression of class II genes [beta 2-microglobulin, hypoxanthine-guanine phosphoribosyl transferase (HPRT), H-ferritin, ubiquitin (UbB), insulin-like growth factor binding protein-4, HNF-1 alpha] is not significantly affected by amino acid limitation. Class III genes [gadd153, beta-actin, ubiquitin (UbC), phosphoglycerate kinase-1, C/EBP alpha, C/EBP beta] exhibit increased expression in response to amino acid limitation. Thus, specific inductive as well as repressive effects on gene expression are quite common in amino acid-limited cells. The observation that all six genes whose expression is liver-specific exhibited decreased expression in amino acid-limited cells suggests a common mode of regulation of these genes by amino acid availability. The strong induction by amino acid limitation of the C/EBP inhibitor gadd153 is of interest in this regard, as increased levels of gadd153 could interfere with C/EBP, which is required for high expression of most liver-specific genes. To investigate further the molecular mechanism for the decrease in albumin mRNA abundance, albumin nuclear transcript levels were quantified in control and tryptophan-limited cells. Tryptophan limitation caused a decrease in albumin nuclear transcript abundance, and this decrease preceded the decrease in albumin mRNA, suggesting that the decrease in albumin mRNA was caused at least partly by a decrease in albumin gene transcription. Additional experiments with actinomycin D indicated that albumin mRNA was also destabilized in the tryptophan-limited cells. Thus, the overall results indicate that the decrease in albumin mRNA in the tryptophan-limited cells is caused by a specific decrease in albumin nuclear transcript abundance and destabilization of albumin mRNA.
 ...
PMID:Effect of amino acid limitation on the expression of 19 genes in rat hepatoma cells. 818 73

A Ubiquitin-like peptide was accidentally isolated from rat bladder by using 5% acetic acid wash while we were isolating antibacterial peptides. The purified molecule was obtained by reverse phase high performance liquid chromatography. Gas phase microsequence analysis indicated the N-terminal sequences of the molecule as follows: MET-GLN-ILE-PHE-VAL-LYS-THR-LEU-THR-GLY-LYS-THR-ILE-THR-LEU- GLU-VAL-GLU-PRO-SER-ASP-THR-ILE-GLU-ASN, which is homologous to human ubiquitin. Ubiquitin plays a role in the differentiation of pre-B lymphocytes, Thus, it is suggested from the findings of this molecule and the endogenous antibacterial polypeptides in mucosa or mucosal epithelium that mucosal epithelium also might be one of immune cells or immunity-associated cells, which may secrete effector molecules directly to kill adherent microbes and produce regulating factors in mucosal immune response.
 ...
PMID:[Rat bladder ubiquitin-like molecule: isolation, purification and N-terminal sequencing]. 824 87

We have isolated and determined DNA sequence for the 5'-flanking regions of three Arabidopsis thaliana polyubiquitin genes, UBQ3, UBQ10, and UBQ11. Comparison to cDNA sequences revealed the presence of an intron in the 5'-untranslated region at the same position immediately upstream of the initiator methionine codon in each of the three genes. An intron at this position is also present in two sunflower and two maize polyubiquitin genes. An intron is also found in the 5'-untranslated regions of several animal polyubiquitin genes, although the exact intron position is not conserved among them, and none are in the same position as those in the higher plant polyubiquitin genes. Chimeric genes containing the 5'-flanking regions of UBQ3, UBQ10, and UBQ11 in front of the coding regions for the reporter enzyme Escherichia coli beta-glucuronidase (GUS) were constructed. When introduced transiently into Arabidopsis leaves via microprojectile bombardment, all resulted in readily detectable levels of GUS activity that were quantitatively similar. The introns of UBQ3 and UBQ10 in the corresponding promoter fragments were removed by replacement with flanking cDNA sequences and chimeric genes constructed. These constructs resulted in 2.5- to 3-fold lower levels of marker enzyme activity after transient introduction into Arabidopsis leaves. The UBQ10 promoter without the 5' intron placed upstream of firefly luciferase (LUX) resulted in an average of 3-fold lower LUX activity than from an equivalent construct with the UBQ10 intron. A UBQ3 promoter cassette was constructed for the constitutive expression of open reading frames in dicot plants and it produced readily detectable levels of GUS activity in transient assays.
 ...
PMID:The intron of Arabidopsis thaliana polyubiquitin genes is conserved in location and is a quantitative determinant of chimeric gene expression. 838 9

During large-scale in vitro translation analysis of a human full-length cDNA bank, we found a clone producing a remarkably smaller translation product than that expected from the open reading frame. The cDNA encodes a polyubiquitin, UbC, composed of nine tandem repeats of the ubiquitin unit. The bank contained twelve UbC cDNAs including four full-length ones. Sequencing analysis of these clones showed that UbC cDNAs can be classified into two types, UbC1 and UbC2, in each of which there are six polymorphic nucleotide variations. The present UbC cDNA was in vitro translated in a rabbit reticulocyte or wheat germ extract to produce a free ubiquitin labeled with [35S]methionine. The labeled ubiquitin could be used as a substrate for thiol ester formation with ubiquitin-activating enzyme E1 or ubiquitin-conjugating enzyme E2.
 ...
PMID:Cloning of human polyubiquitin cDNAs and a ubiquitin-binding assay involving its in vitro translation product. 964 42

Ubiquitin-mediated degradation plays a crucial role in many fundamental biological pathways, including the mediation of cellular responses to changes in environmental conditions. A family of ubiquitin ligase complexes, called SCF complexes, found throughout eukaryotes, is involved in a variety of biological pathways. In Saccharomyces cerevisiae, an SCF complex contains a common set of components, namely, Cdc53p, Skp1p, and Hrt1p. Substrate specificity is defined by a variable component called an F-box protein. The F- box is a approximately 40-amino-acid motif that allows the F-box protein to bind Skp1p. Each SCF complex recognizes different substrates according to which F-box protein is associated with the complex. In yeasts, three SCF complexes have been demonstrated to associate with the ubiquitin-conjugating enzyme Cdc34p and have ubiquitin ligase activity. F-box proteins are not abundant and are unstable. As part of the SCF(Met30p) complex, the F-box protein Met30p represses methionine biosynthetic gene expression when availability of L-methionine is high. Here we demonstrate that in vivo SCF(Met30p) complex activity can be regulated by the abundance of Met30p. Furthermore, we provide evidence that Met30p abundance is regulated by the availability of L-methionine. We propose that the cellular responses mediated by an SCF complex are directly regulated by environmental conditions through the control of F-box protein stability.
 ...
PMID:The abundance of Met30p limits SCF(Met30p) complex activity and is regulated by methionine availability. 1102 56

Acute stimulation of the receptor for the hepatocyte growth factor/scatter factor Met leads to receptor monoubiquitination and down-regulation through the lysosomal degradation pathway. We have determined that the Met receptor undergoes multiple monoubiquitination as opposed to the appendage of polyubiquitin chains. Nevertheless, overexpression of ubiquitin in HEK293T cells enhances the rate of Met receptor degradation, in contrast to a point mutant of ubiquitin (K48R) that cannot form Lys(48)-linked polyubiquitin chains. Furthermore, an enhancement of Met degradation is also seen under conditions where the proteasome is inhibited by lactacystin. We propose that this reflects polyubiquitin-dependent sorting of Met, as the overexpression of ubiquitin but not K48R ubiquitin also restores hepatocyte growth factor-dependent phosphorylation of the endosomal coat protein Hrs from inhibition by lactacystin. Our data indicate a requirement for K48R-linked polyubiquitin for Met endosomal trafficking independent of its canonical function of targeting for proteasomal degradation.
 ...
PMID:The met receptor degradation pathway: requirement for Lys48-linked polyubiquitin independent of proteasome activity. 1546 66

The Golgi-localized, gamma-ear-containing, Arf (ADP-ribosylation factor)-binding (GGA) proteins are clathrin adaptors that mediate the sorting of transmembrane-cargo molecules at the trans-Golgi network and endosomes. Cargo proteins can be directed into the GGA pathway by at least two different types of sorting signals: acidic cluster-dileucine motifs and covalent modification by ubiquitin. The latter modification is recognized by the GGAs through binding to their GAT [GGA and TOM (target of Myb)] domain. Here we report the crystal structure of the GAT domain of human GGA3 in a 1:1 complex with ubiquitin at 2.8-A resolution. Ubiquitin binds to a hydrophobic and acidic patch on helices alpha1 and alpha2 of the GAT three-helix bundle that includes Asn-223, Leu-227, Glu-230, Met-231, Asp-244, Glu-246, Leu-247, Glu-250, and Leu-251. The GAT-binding surface on ubiquitin is a hydrophobic patch centered on Ile-44 that is also responsible for binding most other ubiquitin effectors. The ubiquitin-binding site observed in the crystal is distinct from the Rabaptin-5-binding site on helices alpha2 and alpha3 of the GAT domain. Mutational analysis and modeling of the ubiquitin-Rabaptin-5-GAT ternary complex indicates that ubiquitin and Rabaptin-5 can bind to the GAT domain at two different sites without any steric conflict. This ability highlights the GAT domain as a hub for interactions with multiple partners in trafficking.
 ...
PMID:Structural mechanism for ubiquitinated-cargo recognition by the Golgi-localized, gamma-ear-containing, ADP-ribosylation-factor-binding proteins. 1570 88


1 2 3 4 5 Next >>