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Query: UNIPROT:P06889 (Mol)
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A rapid and sensitive assay was developed to detect CAA-->AAA mutations at codon 61 of Ha-ras. The region surrounding codon 61 was amplified by the polymerase chain reaction (PCR) using one primer containing a mismatch at the second position of codon 60. Using this primer creates an Msel restriction enzyme site if codon 61 carries the C.G-->A.T transversion. An aliquot of the second PCR primer was 5'-end-labeled with 32P to increase the sensitivity of detection of the PCR product. After cleavage with Msel, DNA was electrophoresed on a nondenaturing polyacrylamide gel, and the products were visualized by autoradiography. The sensitivity of this assay was such that the mutation could be detected when present in only one of 200 alleles. DNA samples from spontaneous Crl:CD-1(ICR)BR mouse liver tumors were analyzed using this method. Nine of 38 samples contained the mutation, and in one of those nine, the mutation had not been previously detected by either direct sequencing of tumor DNA or by sequencing the DNA from NIH 3T3 cells transfected with the tumor DNA.
Mol Carcinog 1993
PMID:A sensitive restriction fragment length polymorphism method to detect CAA-->AAA mutations at codon 61 of Ha-ras. 810 30

Simple sequences present in long (> 30 kb) sequences representative of the single-copy genome of five species (Homo sapiens, Caenorhabditis elegans, Saccharomyces cerevisiae, E. coli, and Mycobacterium leprae) have been analyzed. A close relationship was observed between genome size and the overall level of sequence repetition. This suggested that the incorporation of simple sequences had accompanied increases of genome size during evolution. Densities of simple sequence motifs were higher in noncoding regions than in coding regions in eukaryotes but not in eubacteria. All five genomes showed very biased frequency distributions of simple sequence motifs in all species, particularly in eukaryotes where AAA and TTT predominated. Interspecific comparisons showed that noncoding sequences in eukaryotes showed highly significantly similar frequency distributions of simple sequence motifs but this was not true of coding sequences. ANOVA of the frequency distributions of simple sequence motifs indicated strong contributions from motif base composition and repeat unit length, but much of the variation remained unexplained by these parameters. The sequence composition of simple sequences therefore appears to reflect both underlying sequence biases in slippage-like processes and the action of selection. Frequency distributions of simple sequence motifs in coding sequences correlated weakly or not at all with those in noncoding sequences. Selection on coding sequences to eliminate undesirable sequences may therefore have been strong, particularly in the human lineage.
J Mol Evol 1995 Dec
PMID:The contribution of slippage-like processes to genome evolution. 858 2

The complete mitochondrial DNA (mtDNA) molecule of the gorilla was sequenced. The entire sequence, 16,412 nucleotides, was determined by analysis of natural (not polymerase chain reaction) restriction fragments covering the whole molecule. The sequence was established from one individual and thus nonchimeric. After comparison with the COII gene of gorilla specimens with known geographical origin, the sequence was identified as characteristic of the Western lowland gorilla, Gorilla gorilla gorilla. With the exception of the NADH2 gene, all genes have a methionine start codon. The inferred start codon of NADH2 is ATT (isoleucine). The COIII, NASDH4, and cytochrome b genes are not terminated by a stop codon triplet, and the COI gene is probably terminated by an AAA triplet rather than by a regular stop codon. The great majority of genic sequences (rRNAs, peptide-coding genes, tRNAs) of the complete mtDNAs of Gorilla, Pan, and Homo show a greater similarity between Pan and Homo than between either of these genera to Gorilla. The analysis of the peptide-coding genes suggest that relative to comparison between Homo and Pan a certain degree of transition saturation has taken place in codon position 3 in comparisons between Gorilla to either Homo or Pan.
Mol Biol Evol 1996 May
PMID:A complete sequence of the mitochondrial genome of the western lowland gorilla. 867 44

The zona pellucida (ZP) is an extracellular matrix surrounding the mammalian oocyte. It is involved in the sperm-egg adhesion phenomenon, induces the acrosome reaction, and participates in the late blockage to polyspermy. Thus, during the process of fertilization the cortical reaction is induced and the biochemical and biological properties of the ZP are modified. Some of these changes have been suggested to prevent the polyspermy. However, the mechanisms behind most of these changes are not well understood. Carbohydrate residues of the ZP glycoproteins have been shown to play a key role in the early step of fertilization. In the present study, the changes produced in the terminal oligosaccharide sequences of the rat ZP glycoproteins after in vivo fertilization were investigated by means of lectin-gold cytochemistry. A comparative quantitative analysis of the density of labeling in the ZP before and after fertilization was carried out by automatic counting of gold particles. The ZP of fertilized and unfertilized eggs were labeled by a battery of lectins including PNA, LFA, MAA, AAA, DSA, RCA I, and WGA. For all lectin studied in both fertilized and unfertilized eggs the labeling was preferentially located in the inner region of the ZP. After fertilization, binding of PNA, LFA, MAA, AAA, and DSA decreased in both inner and outer regions of the ZP. Labeling of RCA I-binding sites only decreased in the inner ZP, whereas reactivity to WGA was increased in the inner ZP, whereas reactivity to WGA was increased in the inner area of the ZP. Digestion of the thin-sections with neuraminidase prior to labeling with WGA resulted in a decrease of labeling for WGA binding sites. However, the labeling density of WGA binding sites was similar in both unfertilized and fertilized eggs upon treatment with neuraminidase. The present results demonstrate that the oligosaccharide chains contained in the rat ZP are modified after fertilization of the oocyte. Cortical granules of the oocytes might be involved in these modifications by two mechanisms: 1) by hydrolysis of terminal carbohydrate residues of ZP glycoproteins by specific glycosidases contained in the granules; and 2) by addition of new glycoproteins to the ZP after the exocytosis of the cortical granules (cortical reaction).
Mol Reprod Dev 1996 Jul
PMID:Modifications of the lectin binding pattern in the rat zona pellucida after in vivo fertilization. 885 7

Footprinting titration experiments have been used to estimate microscopic binding constants (KA) for interactions of the ligands Hoechst 33258, DAPI and pentamidine with the 167-mer of the EcoRl-Rsal restriction fragment of the plasmid pBR322. The symmetric base sequence AATTAA yielded the lowest KA values while binding sites which contain an AAA-segment displayed higher binding constants. The accommodation of an adjacent G-C base pair to the ATTT-sequence does not significantly interfere with the stability of the DNA-drug complex. The footprint pattern of the compound Hoechst 33258 shows a peculiarity. Complex formation at low drug concentrations (up to 0.5 mu M) is accompanied by distinct protection sites in the DNA fragment against DNAasel digestion, while at higher drug concentration (up to 5.0 mu M) at the same sites the cleavage activity of the enzyme is enhanced. This is discussed in terms of a conformational change of DNA induced by two concentration-dependent binding modes (AT-specific minor groove binding at low drug concentration and GC-specific interaction at a higher one).
Biochem Mol Biol Int 1996 Feb
PMID:Determination of microscopic binding constants at individual DNA base sequences for the minor groove binders Hoechst 33258, DAPI and pentamidine. 893 26

The DNA undecamers GTACAAAGTAC (AAA 11-mer) and GTACGAGGTAC (GAG 11-mer) have been studied in solution by high-resolution NMR spectroscopy. Both duplexes form stable hairpins containing single deoxyadenosine loops and stems containing five base-pairs that are closed at the loop end by sheared AxA and GxC pairs, respectively. These molecules thus contain new AAA and GAG loop turn motifs. All protons, including the chiral H5'/H5" protons of the loop residues, were assigned using NOESY, DQF-COSY and heteronuclear 1H-31P COSY experiments. The backbone torsion angles were constrained using experimental data from NOE crosspeaks, three-bond 1H-1H coupling constants and four-bond 1H-31P coupling constants and four-bond 1H-31P coupling constants. The AAA and GAG 11-mers form similar structures in solution. The detailed structure of the AAA 11-mer was determined by the combined use of NMR, distance geometry and energy minimization methods. This structure exhibits good stacking of the loop adenosine base on the closing 5Ax7A sheared pair, with the 6A base stacking on the 5A base and the 6A deoxyribose stacking with the 7A base. All sugars in the AAA 11-mer hairpin adopt the typical DNA C2'-endo conformation and a sharp backbone turn occurs between residues 6A and 7A. This loop turn is brought about mainly by a change in the backbone phosphate torsion angles from zeta(g-) alpha(g-) to zeta(g+) alphat(g+) at the turn. The gamma torsion angle of residue 7A in the closing sheared pair also changes from gauche+ to trans. In Pu1NPu2 loop turns of the GCA, AAA and GAG types, the chemical shift of the H4' proton of the loop deoxyribose depends on the nature of Pu2; this reflects the stacking of the loop sugar on the Pu2 base and the different ring current effects of A or G in this position.
J Mol Biol 1996 Dec 20
PMID:Hairpin loops consisting of single adenine residues closed by sheared A.A and G.G pairs formed by the DNA triplets AAA and GAG: solution structure of the d(GTACAAAGTAC) hairpin. 900 Jun 25

A new Korean isolate of cymbidium mosaic virus (denoted as CymMV-K2), a member of potexviruses, was identified and isolated from a Korean cultivar of Cymbidium species When the nucleotide sequence of the 3'-terminal region of the viral RNA was compared with those of the corresponding regions of two Singaporean isolates (denoted as CymMV-S1 and CymMV-S2) and a Korean isolate (denoted as CymMV-K1), the nucleotide sequence of the coat protein gene of CymMV-K2 was highly homologous to other cymbidium mozaic viruses (92.9%-96.7% homology). The coat protein of CymMV-K2 and CymMV-S2 consists of 223 amino acids, while the coat protein of CymMV-K1 and CymMV-S1 consists of 220 amino acids. This difference was caused by deletions of 5 nucleotides in the coat protein open reading frame (ORF) of CymMV-S1 and CymMV-K1, when compared with CymMV-K2 and CymMV-S2. These deletions result in changes of the deduced amino acid sequence and the length of the coat protein. The 3'-noncoding region of the CymMV-K2, which contains sequences involved in the replication and polyadenylation of viral RNA, was compared with those of other cymbidium mosaic viruses. No canonical polyadenylation signal was found in the 3'-noncoding region of CymMV-K2, whereas in other CymMVs AAUAAA boxes, are present at the end of RNA with their AAA portions as the first A residue of the poly(A) tail.
Mol Cells 1997 Feb 28
PMID:Coat protein gene and 3'-noncoding region of a new Korean isolate of cymbidium mosaic virus. 908 62

The enzyme steroid 5 alpha-reductase, via NADPH, catalyses the conversion of testosterone to dihydrotestosterone, which is required for the embryonic differentiation of the external male genitalia and the prostate. An impairment of this reaction causes a form of male pseudohermaphroditism in which genetic males differentiate predominantly as phenotypic females. Molecular analysis of the 5 alpha-reductase type 2 gene in a patient with confirmed biochemical 5 alpha-reductase deficiency has resulted in the identification of a novel mutation, GAA to AAA, at codon 200. This mutation produces an amino acid change from glutamic acid to lysine, and may affect the ability of the enzyme to bind its co-factor.
Mol Pathol 1997 Feb
PMID:Male pseudohermaphroditism resulting from a novel mutation in the human steroid 5 alpha-reductase type 2 gene (SRD5A2). 920 14

The AAA proteins (ATPases Associated with a variety of cellular Activities) are found in eubacterial, archaebacterial, and eukaryotic species and participate in a large number of cellular processes, including protein degradation, vesicle fusion, cell cycle control, and cellular secretory processes. The AAA proteins are characterized by the presence of a 230 to 250-amino acid ATPase domain referred to as the Conserved ATPase Domain or CAD. Phylogenetic analysis of 133 CAD sequences from 38 species reveal that AAA CADs are organized into discrete groups that are related not only in structure but in cellular function. Evolutionary analyses also indicate that the CAD was present in the last common ancestor of eubacteria, archaebacteria, and eukaryotes. The eubacterial CADs are found in metalloproteases, while CAD-containing proteins in the archaebacterial and eukaryotic lineages appear to have diversified by a series of gene duplication events that lead to the establishment of different functional AAA proteins, including proteasomal regulatory, NSF/Sec, and Pas proteins. The phylogeny of the CADs provides the basis for establishing the patterns of evolutionary change that characterize the AAA proteins.
J Mol Evol 1997 Nov
PMID:The evolution of the conserved ATPase domain (CAD): reconstructing the history of an ancient protein module. 934 2

Two peroxins of the AAA family, PpPex1p and PpPex6p, are required for peroxisome biogenesis in the yeast Pichia pastoris. Cells from the corresponding deletion strains (Pp delta pex1 and Pp delta pex6) contain only small vesicular remnants of peroxisomes, the bulk of peroxisomal matrix proteins is mislocalized to the cytosol, and these cells cannot grow in peroxisome-requiring media (J. A. Heyman, E. Monosov, and S. Subramani, J. Cell Biol. 127:1259-1273, 1994; A. P. Spong and S. Subramani, J. Cell Biol. 123:535-548, 1993). We demonstrate that PpPex1p and PpPex6p interact in an ATP-dependent manner. Genetically, the interaction was observed in a suppressor screen with a strain harboring a temperature-sensitive allele of PpPEX1 and in the yeast two-hybrid system. Biochemially, these proteins were coimmunoprecipitated with antibodies raised against either of the proteins, but only in the presence of ATP. The protein complex formed under these conditions was 320 to 400 kDa in size, consistent with the formation of a heterodimeric PpPex1p-PpPex6p complex. Subcellular fractionation revealed PpPex1p and PpPex6p to be predominantly associated with membranous subcellular structures distinct from peroxisomes. Based on their behavior in subcellular fractionation experiments including flotation gradients and on the fact that these structures are also present in a Pp delta pex3 strain in which no morphologically detectable peroxisomal remnants have been observed, we propose that these structures are small vesicles. The identification of vesicle-associated peroxins is novel and implies a role for these vesicles in peroxisome biogenesis. We discuss the possible role of the ATP-dependent interaction between PpPex1p and PpPex6p in regulating peroxisome biogenesis events.
Mol Cell Biol 1998 Feb
PMID:Two AAA family peroxins, PpPex1p and PpPex6p, interact with each other in an ATP-dependent manner and are associated with different subcellular membranous structures distinct from peroxisomes. 944 90


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