Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q07644 (polypeptide)
 72,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using synthetic antisense RNA from the 5'-untranslated region of the beta-tubulin gene as probe in gel retardation assays, a heat stable RNA-binding factor was identified in promastigotes of the kinetoplastid protozoan Leishmania donovani. The same or similar factors interact with several small ribosomal RNA (srRNA) species and, more weakly, with tRNA, as shown by binding and competition experiments. Deletion analysis indicated involvement of repeated purine-rich motifs on the antisense RNA, in the reaction. Related, conserved motifs occur on at least two of the srRNAs. By a modified Western blot assay, the RNA-binding species was identified as a single, small polypeptide. The activity is apparently specific for the promastigote stage of the parasite, being undetectable in amastigotes. The properties of this RNA-binding factor suggest that it is a novel, previously uncharacterized protein.
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PMID:Interaction of small ribosomal and transfer RNAs with a protein from Leishmania donovani. 820 69

The complete nucleotide sequence of a benomyl-resistant allele of the Septoria nodorum beta-tubulin gene (tubAR) has been determined including 745 and 1024 nucleotides 5' and 3' to the tubAR coding region, respectively. tubAR encodes a 447 amino acid polypeptide which shows a high degree of homology with other fungal beta-tubulins. The gene contains three introns at codons 4, 12 and 53, uses 48 of the possible 61 sense codons and has a GC content of 59.1% in its coding region. S1 nuclease mapping has identified two transcriptional start sites 80 bp and 83 bp upstream of the translation start, and a transcriptional termination site 192 bp downstream of the stop codon. The two transcriptional start sites lie just 8 bp and 5 bp downstream of a CT motif consisting of 18 pyrimidine nucleotides interrupted by a single adenine. The wild-type allele tubA+ has been cloned using the polymerase chain reaction and the mutation producing the benomyl-resistant phenotype of tubAR mapped to a C to T transition at the first position of codon 6, resulting in a histidine to tyrosine amino acid substitution.
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PMID:Molecular analysis of the Septoria nodorum beta-tubulin gene and characterization of a benomyl-resistance mutation. 845 67

The cytoplasmic microtubules of the cold-adapted Antarctic fishes, unlike those of homeotherms and temperate poikilotherms, assemble and function at body temperatures in the range -1.8 to +2 degrees C. To determine whether alterations to the primary sequence of beta tubulin may contribute to enhancement of microtubule assembly at cold temperatures, we have cloned and sequenced a 1.8-kilobase neural beta-chain cDNA, Ncn beta 1, from an Antarctic rockcod, Notothenia coriiceps neglecta. Based on nucleotide sequence homology, Ncn beta 1 probably corresponds to a class-II beta-tubulin gene. The 446-residue beta chain encoded by Ncn beta 1 is closely related (sequence homology approximately 95%) both to the neural class-I/II isotypes and to the neural/testicular class-IV variants of higher vertebrates, but the sequence of its carboxy-terminal isotype-defining region (residues 431-446) has diverged markedly (> or = 25% change relative to the I/II/IV referents). Furthermore, the Ncn beta 1 polypeptide contains six unique amino-acid substitutions (five conservative, one nonconservative) not found in other vertebrate brain isotypes, and the carboxy-terminal region possesses a unique tyrosine inserted at position 442. We conclude that Ncn beta 1 encodes a class-II beta tubulin that contains sequence modifications, located largely in its interdimer contact domain, that may contribute to cold adaptation of microtubule assembly.
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PMID:Divergent neural beta tubulin from the Antarctic fish Notothenia coriiceps neglecta: potential sequence contributions to cold adaptation of microtubule assembly. 846 23

The rhizoxin (RZX)-binding site on porcine brain tubulin was investigated by photoaffinity labeling with the 5-azido-1-naphthalene sulfonyl (azidodansyl) derivative of RZX, nor-rhizoxin-22-al-5'-azidonaphthalene-1'-sulfonylhydrazo ne (azidodansylrhizoxin: Adan-RZX). Upon ultraviolet irradiation, Adan-RZX generates a highly reactive nitrene, which irreversibly binds to an amino acid residue(s) near the RZX-binding site. The label was found to be on beta-tubulin. Enzymatic digestion of the labeled tubulin generated only one major fluorescent peak on C18 reverse phase HPLC analysis. The labeled site(s) was mapped by using various combinations of highly specific peptidases in succession. That is, the labeled fragment generated by the first peptidase was purified by HPLC and exposed to a second peptidase; if the retention time in HPLC changed after the second digestion, the fragment generated in the first digestion must have contained the recognition site(s) of the second enzyme. From the results of these successive digestions and the known polypeptide sequences, we could identify the labeled fragment as Met-363-Lys-379 of beta-tubulin. This peptidase combination technique should be widely applicable.
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PMID:Identification of the fragment photoaffinity-labeled with azidodansyl-rhizoxin as Met-363-Lys-379 on beta-tubulin. 847 Oct 64

Microtubule inhibitors are active against the human malarial parasite Plasmodium falciparum, but whether these drugs actually interact with parasite tubulins is not known. It has not previously been possible to produce mg quantities of isolated, soluble tubulin subunits for drug-binding experiments. A cDNA encoding P falciparum beta-tubulin was expressed and the protein secreted in Bacillus brevis. With the addition of EGTA to the culture medium, which increases shedding of proteins from the cell surface, up to 2 mg/l recombinant beta-tubulin was obtained in supernatants. It is not clear why B brevis is able to secrete this normally cytoplasmic protein, but the secretion levels of recombinant proteins may be related to the net charge of the first few residues of the mature polypeptide.
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PMID:Expression and secretion of malarial parasite beta-tubulin in Bacillus brevis. 858 54

This study reports the immunocytochemical localization of the retinoblastoma gene product within synchronized normal human keratinocytes. Data suggest that mitotic spindles function in the transport of the retinoblastoma tumor suppressor gene product during cell division. A diffuse anti-pRB reactivity was detected within the nuclei of G1-phase keratinocytes, although staining was not evident within the nucleoli. During S-phase and G2-phase the anti-pRB reactivity was localized to discrete regions within the nuclear compartment. The anti-pRB reactivity of M-phase cells was localized to the mitotic spindles and microtubule nucleation centers. Immunoprecipitation and Western blotting of the pRB antigen from synchronized keratinocytes showed that the apparent polypeptide molecular weight of pRB increased from 105 kDa during G1-phase to 115 kDa during M-phase. Immunoprecipitation of the pRB antigen from mitotic spindles resulted in the coprecipitation of two polypeptides with apparent polypeptide molecular weights of 115 and 50 kDa. Western blotting of the immunoprecipitates from purified keratinocyte mitotic spindles showed that beta-tubulin was the 50-kDa polypeptide associated with hyperphosphorylated pRB.
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PMID:Translocation of the retinoblastoma gene product during mitosis. 860 98

In filarial worms, as in other eukaryotes, microtubules are essential multifunctional components. The major protein of microtubules is tubulin, a heterodimer of two distinct polypeptides, alpha and beta. Tubulin is particularly important in helminthic parasites as a target for anthelminthic benzimidazoles, which bind to it and inhibit microtubule assembly. Two genomic Onchocerca gibsoni libraries were constructed in lambda NM1149 (EcoRI and HindIII). Three clones accounted for the entire gene: one from the EcoRI library (using a Plasmodium falciparum probe) containing the central part of the gene, and two from the HindIII library (using as probes PCR amplified fragments from the ends of the EcoRI clone) which, respectively, contained the 5'- and 3'-ends of the gene. The sequencing procedure for the EcoRI clone relied on the construction of a double-digested DraI/HindIII shotgun library. A number of recombinants were sequenced and aligned with each other for comparison. The sequencing of the overlapping 5'- and 3'-end clones was done by using a series of oligonucleotides. The sequence of the O. gibsoni beta-tubulin gene was completely determined, revealing an exceptionally complex structure as compared to the known beta-tubulin genes: 5,797 base pairs containing 12 exons and 11 introns. The deduced polypeptide is 444 amino acids long, and its sequence is highly conserved. The position of some introns appear to demarcate functional domains within the protein.
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PMID:Organization and structure of an Onchocerca beta-tubulin gene. 863 75

A beta-tubulin gene from a UV-irradiated benomyl-resistant mutant of Fusarium moniliforme was isolated, cloned, and sequenced. The gene encodes a 446-amino-acid polypeptide with homology to other fungal beta-tubulins. RNA blot analysis showed expression of the gene during vegetative growth and conidial germination but no expression during conidiation. A point mutation, which likely confers benomyl resistance, has been identified in the cloned gene; this mutation results in a single amino acid substitution of asparagine for tyrosine at position 50. Expression of benomyl resistance in the mutant was also cold sensitive. Sexual crosses betweeen the mutant and a wild-type strain indicated cosegregation of benomyl resistance and cold sensitivity.
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PMID:Isolation of a beta-tubulin gene from Fusarium moniliforme that confers cold-sensitive benomyl resistance. 870

Actin and tubulin polypeptide chains acquire their native conformation in the presence of the chaperonin containing TCP-1 (CCT) and, in the case of alpha- and beta-tubulin additional protein cofactors. We recently identified one of these cofactors, termed cofactor A, that is required for the proper folding of the beta-tubulin chain [Gao et al. (1994) J. Cell. Biol. 125, 989-996]. We show here that cofactor A, a monomeric protein that has no measurable affinity for nucleotides, is a highly conserved protein among vertebrates. Its NH2-terminal region is essential for the structural integrity of the protein and consequently for its activity. We demonstrate that cofactor A does not interact with CCT nor does it affect the intrinsic ATPase activity of CCT, alone or in the presence of different target proteins. Thus, unlike GroES, cofactor A does not modulate or coordinate ATP hydrolysis. It does not act as a nucleotide exchange factor or a catalyst in tubulin folding. Rather, we demonstrate that cofactor A participates in the tubulin folding process by interacting with a folding intermediate of beta-tubulin that is released from CCT. Our data imply that cofactor A is a chaperone involved in tubulin folding.
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PMID:Cofactor A is a molecular chaperone required for beta-tubulin folding: functional and structural characterization. 875 98

Tubulin folding requires two chaperone systems, i.e., the 900 kDa cytosolic chaperonin referred to as the TCP-1 complex or TRiC which facilitates folding of the alpha- and beta-tubulin subunits and a ca. 180 kDa complex which facilitates further assembly into heterodimer. beta-Tubulin mutants were expressed in rabbit reticulocyte lysates, and the effect of C-terminal, N-terminal, and internal deletions on the binding of beta-tubulin polypeptides to the 900 and 180 kDa complexes was ascertained. Proteolytic studies of chaperonin-bound beta-tubulin were also implemented. These studies support the concept of quasi-native chaperonin-bound intermediates [Tian et al. J. Biol. Chem. (1995) 270, 1-4]. Three "domains" similar in size to the domains in the native protein were implicated in facilitated folding: i.e., an internal or "M-domain" composed of residues approximately 140-260 which binds to TRiC; a "C-domain" composed of residues approximately 300-445 which interacts less strongly with TRiC and may contain regulatory sequences for tubulin release from the chaperonin; and an "N-domain" composed of residues approximately 1-140 which apparently does not interact with TRiC but does interact with the 180 kDa complex. The major TRiC-interacting region, residues approximately 150-350 (the "interactive core"), overlapped portions of the M- and C-domains and included a putative hydrophobic-rich interdomain segment which may be a preferential site of interaction with TRiC. This segment may also be important for microtubule assembly and/or tubulin dimer formation. Removal of two residues from the N-terminal end or ca. 27 residues from the C-terminal and caused the polypeptide to arrest on TRiC. It is proposed that N- and C-terminal regions of beta-tubulin structurally interact with TRiC-binding region approximately 150-350 to inhibit binding to TRiC.
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PMID:Newly-synthesized beta-tubulin demonstrates domain-specific interactions with the cytosolic chaperonin. 896 52


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