Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Cdc2 protein kinase requires cyclin binding for activity and also binds to a small protein, Suc1. Charged-to-alanine scanning mutagenesis of Cdc2 was used previously to localize cyclin A- and B- and Suc1-binding sites (B. Ducommun, P. Brambilla, and G. Draetta, Mol. Cell. Biol. 11:6177-6184, 1991). Those sites were mapped by building a Cdc2 model based on the crystallographic coordinates of the catalytic subunit of cyclic AMP-dependent protein kinase (cAPK) (D. R. Knighton, J. Zheng, L. F. Ten Eyck, V. A. Ashford, N.-H. Xuong, S. S. Taylor, and J. M. Sowadski, Science 253:407-414, 1991). On the basis of this model, additional mutations were made and tested for cyclin A and Suc1 binding and for kinase activity. Mutations that interfere with cyclin A binding are localized primarily on the small lobe near its interface with the cleft and include an acidic patch on the B helix and R-50 in the highly conserved PSTAIRE sequence. Two residues in the large lobe, R-151 and T-161, influence cyclin binding, and both are at the surface of the cleft near its interface with the PSTAIRE motif. Cyclin-dependent phosphorylation of T-161 in Cdc2 is essential for activation, and the model provides insights into the importance of this site. T-161 is equivalent to T-197, a stable phosphorylation site in cAPK. On the basis of the model, cyclin binding very likely alters the surface surrounding T-161 to allow for T-161 phosphorylation. The two major ligands to T-197 in cAPK are conserved as R-127 and R-151 in Cdc2. The equivalent of the third ligand, H-87, is T-47 in the PSTAIRE sequence motif. Once phosphorylated, T-161 is predicted to play a major structural role in Cdc2, comparable to that of T-197 in cAPK, by assembling the active conformation required for peptide recognition. The inhibitory phosphorylation at Y-15 also comes close to the cleft interface and on the basis of this model would disrupt the cleft interface and the adjacent peptide recognition site rather than prevent ATP binding. In contrast to cyclin A, both lobes influence Suc1 binding; however, the Suc1-binding sites are far from the active site. Several mutants map to the surface in cAPK, which is masked in part by the N-terminal 40 residues that lie outside the conserved catalytic core. The other Suc1-binding site maps to the large lobe near a 25-residue insert and includes R-215.
Mol Cell Biol 1993 Aug
PMID:A three-dimensional model of the Cdc2 protein kinase: localization of cyclin- and Suc1-binding regions and phosphorylation sites. 833 38

The ref(2)P locus (2-54.2) is polymorphic for two allelic forms in natural populations of Drosophila melanogaster, ref(2)Po and ref(2)Pp. The latter allele confers resistance to the rhabdovirus sigma infecting wild populations. Previous work, based on a small sample of prescreened restrictive (resistant) and permissive (susceptible) alleles, identified a large number of amino acid replacement changes (7) relative to synonymous changes (1). Such protein variability could be the result of variation-enhancing selection. To further test the selection hypothesis, we have examined the DNA sequences of ten randomly chosen lines of D. melanogaster and one line of D. simulans. Nine of the ten lines are permissive; D. simulans does not harbor the virus. The melanogaster alleles contain 4 synonymous changes, 19 noncoding changes, and 13 amino acid replacement changes, indicating a relatively high level of polymorphism. Three sequenced restrictive alleles have nearly identical sequences, indicating that they are relatively young. Compared to the permissive alleles, they share only a complex deletion at codon 34, CAG-AAT to GGA, which our analysis indicates to be the site conferring the restrictive phenotype. Patterns of polymorphism and divergence differ from neutral predictions by several criteria for the amino terminal region, which contains the complex deletion (codons 1-91), but not the remainder of the protein (codons 92-599). We find a higher rate of evolution on the D. melanogaster lineage than on the D. simulans lineage. The relatively large amount of both replacement and silent polymorphism in the permissive alleles and the lack of divergence between permissive and restrictive alleles suggests that the sigma virus and ref(2)P may be engaged in an evolutionary race in which new restrictive alleles are continually arising but are relatively short-lived.
Mol Biol Evol 1996 Jan
PMID:Molecular population genetics of ref(2)P, a locus which confers viral resistance in Drosophila. 858 91

Genetic markers based upon PCR amplification of short tandem repeat-containing sequence tagged sites (STSs) have become the standard for genetic mapping. We have completed a survey based on the direct isolation of representative members of each of the 10 trinucleotide repeat classes to determine their relative abundance, repeat size distribution, and general utility as genetic markers. Trinucleotide repeats, depending on the repeat class, are one to two orders of magnitude less frequent than (AC)n repeats. The average size of trinucleotide repeats sequenced was less than 15 repeat units in length, and only three of the STSs developed for this study demonstrated more than 25 repeats units. The (AAT)n class of repeats are the most abundant and also the most frequently polymorphic. Other classes of trinucleotide repeat classes observed to be frequently polymorphic include (AAC)n, (ACT)n, (ATC)n and (AAG)n; however, the relative abundance of these classes is less than that observed for the (AAT)n class of repeats. Based upon this initial survey, we have initiated saturation cloning of the (AAT)n class of repeats. At the time of submission of this manuscript, we have developed, as part of the Cooperative Human Linkage Center (CHLC), more than 415 new high heterozygosity (AAT)n genetic markers (more than two alleles in four individuals) and 200 new low heterozygosity (AAT)n STSs from this larger screening effort combined with the initial survey.
Hum Mol Genet 1995 Oct
PMID:Survey of trinucleotide repeats in the human genome: assessment of their utility as genetic markers. 859 3

A recessive mutant with white leaves was identified in a screen of a population of T-DNA-tagged Arabidopsis thaliana plants. The mutation is lethal, but plants develop almost to maturity under sterile conditions. The white areas in leaves are devoid of developed chloroplasts, but the plants frequently develop green sectors which contain green chloroplasts. Molecular characterisation of the affected gene revealed that the mutant is allelic to pale cress (pac), a recently described mutation, and was therefore named pac-2. Sequencing of cDNAs and the genomic region revealed several noteworthy features of this genetic locus. In pac-2 the T-DNA had inserted in the region of the promoter and abolished transcription of the PAC gene completely. Cytokinin induced greening in mature, white homozygous pac-2 plants, and therefore is likely to be responsible for the greening observed in callus and shoots induced on roots from such plants. However, the PAC transcript was found to be absent in both white leaves and green callus. Thus, since cytokinin induced greening in the absence of PAC RNA this plant hormone appears to be able to bypass PAC function.
Mol Gen Genet 1996 Jul 19
PMID:Characterisation of a new allele of pale cress and its role in greening in Arabidopsis thaliana. 870 59

The alkaline single-cell gel (SCG) assay, which determines DNA damage in mice treated with 100 mg/kg methyl methanesulfonate (MMS), was run by using three power supplies from Bio-Rad (models 3000Xi, 200/2.0, and Power Pac 300). Comparisons of the results obtained from the use of these power supplies showed differences in mean DNA tail length to width ratios and profiles of these ratios in individual cells. Model 200/2.0 power supply appeared to enhance significantly the sensitivity of the assay. In purchasing power supplies, there is a need to evaluate their effect on the sensitivity of the test.
Environ Mol Mutagen 1996
PMID:Comparison of three power supplies used for the single-cell gel assay. 884 97

A nuclear tRNA(Lys) gene from Arabidopsis thaliana was cloned and mutated so as to express tRNAs with altered anticodons which bind to a UAG nonsense (amber) codon and to the Arg (AGG), Asn (AAC,AAT), Gln (CAG) or Glu (GAG) codons. Concomitantly, a codon in the firefly luciferase gene for a functionally important Lys was altered to an amber codon, or to Arg, Asn, Gln, Glu, Thr and Trp codons, so as to construct reporter genes reliant upon incorporation of Lys. The altered tRNA(Lys) and luciferase genes were introduced into Nicotiana benthamiana protoplasts and expression of the mutated tRNAs was verified by translational suppression of the mutant firefly luciferase genes. Expression of the amber suppressor tRNA(LysCUA) from non-replicative vectors promoted 10-40% suppression of the luciferase nonsense reporters while expression of the amber and missense tRNA(Lys) suppressor genes from a geminivirus vector capable of replication promoted 30-80% suppression of the luciferase nonsense reporter and up to 10% suppression of the luciferase missense reporters with Arg, Asn, Gln and Glu codons.
Plant Mol Biol 1998 Jan
PMID:Nonsense and missense translational suppression in plant cells mediated by tRNA(Lys). 948 71

In this report we describe a sequence (PNG22) highly similar to the Phospholipase C beta3 Neighboring Gene (PNG). We also report that PNG22 is located in the q12 region on chromosome 22 between markers D22S1144 and D22S280. This finding explains that PNG probes cross hybridize to sequences on chromosome 22. Fine mapping using our sequence data and the complete sequence of a PAC clone (DJ515N1), located in this region, determined that PNG22 is located in intron 15 of the LIMK-2 gene. PNG22 is 93% homologous to PNG, however it do not have the introns described for the PNG gene, instead matching the cDNA sequence. This leads us to suggest that PNG22 probably represents a PNG pseudogene. In this report we also list the exon intron borders and the genomic structure of LIMK-2 and place it on the Sanger Center chromosome 22 Physical map. It also explains the finding that PNG probes cross hybridize to sequences on chromosome 22.
Biochem Mol Biol Int 1998 Mar
PMID:A sequence highly similar to PNG is located on chromosome 22q12 in intron 15 of the LIMK-2 gene. 955 20

Fugu rubripes (Fugu) has one of the smallest recorded vertebrate genomes and is an economic tool for comparative DNA sequence analysis. Initial characterization of 128 kb of Fugu DNA attributed the compactness of this genome, in part, to a sparseness of repetitive DNA sequence compared with mammalian genomic sequences. This paper describes a new and comprehensive analysis in which 501 theoretically possible microsatellites with a repeat unit of one to six bases were used to query two orders of magnitude more Fugu DNA (i.e. 11.338 Mb). A total of 6042 microsatellites were identified and categorized. In decreasing order, the 20 most frequently occurring microsatellites are AC, A, C, AGG, AG, AGC, AAT, AAAT, ACAG, ACGC, ATCC, AAC, ATC, AGGG, AAAG, AAG, AAAC, AT, CCG and TTAGGG. The 20 most frequently occurring microsatellites represent 81.79% of all microsatellites identified. Our results indicate that one microsatellite occurs every 1.876 kb of DNA in Fugu, 11.55% of the microsatellites are detected in open reading frames that are predicted protein coding regions. With respect to the proportion of microsatellites present in open reading frames and the total abundance (bp) of all microsatellites, the genome of Fugu is similar to the genome of many other vertebrate species. Previous estimates performed indicate that approximately 1% of many vertebrate genomes are comprized of microsatellite sequences. However, many differences prevail in the abundance and frequency of the individual microsatellite classes. Many of the frequently occurring microsatellites in Fugu are known to code in other species for regions in proteins such as transcription factors, whilst others are associated with known functions, such as transcription factor binding sites and form part of promoter regions in DNA sequences of genes. Therefore, it is likely that such repeats in genomes have a role in the evolution of genes, regulation of gene expression and consequently the evolution of species.
J Mol Biol 1998 May 15
PMID:The identification and characterization of microsatellites in the compact genome of the Japanese pufferfish, Fugu rubripes: perspectives in functional and comparative genomic analyses. 961 46

A soybean cDNA clone, pSAT1, which encodes both the cytosolic and glyoxysomal isozymes of aspartate aminotransferase (AAT; EC 2.6.1.1) was isolated. Genomic Southern blots and analysis of genomic clones indicated pSAT1 was encoded by a single copy gene. pSAT1 contained an open reading frame with ca. 90% amino acid identity to alfalfa and lupin cytosolic AAT and two in-frame start codons, designated ATG1 and ATG2. Alignment of this protein with other plant cytosolic AAT isozymes revealed a 37 amino acid N-terminal extension with characteristics of a peroxisomal targeting signal, designated PTS2, including the modified consensus sequence RL-X5-HF. The second start codon ATG2 aligned with previously reported start codons for plant cytosolic AAT cDNAs. Plasmids constructed to express the open reading frame initiated by each of the putative start codons produced proteins with AAT activity in Escherichia coli. Immune serum raised against the pSAT1-encoded protein reacted with three soybean AAT isozymes, AAT1 (glyoxysomal), AAT2 (cytosolic), and AAT3 (subcellular location unknown). We propose the glyoxysomal isozyme AAT1 is produced by translational initiation from ATG1 and the cytosolic isozyme AAT2 is produced by translational initiation from ATG2. N-terminal sequencing of purified AAT1 revealed complete identity with the pSAT1-encoded protein and was consistent with the processing of the PTS2. Analysis of cytosolic AAT genomic sequences from several other plant species revealed conservation of the two in-frame start codons and the PTS2 sequence, suggesting that these other species may utilize a single gene to generate both cytosolic and glyoxysomal or peroxisomal forms of AAT.
Plant Mol Biol 1998 May
PMID:Characterization of a single soybean cDNA encoding cytosolic and glyoxysomal isozymes of aspartate aminotransferase. 962 Feb 68

The pale cress (pac) mutation arrests chloroplast development at an early stage in Arabidopsis thaliana and leads to a white phenotype. Chlorophyll fluorescence measurements demonstrated that the photosynthetic apparatus was impaired. The mutation did not reduce transcription of nuclear genes with photosynthetic function. However, distinct chloroplast-encoded transcripts were affected. The mutation mainly changed the maturation pattern, but the abundance of specific transcripts was also reduced. The defects observed imply a specific role for PAC in chloroplast mRNA maturation. PAC is encoded by a nuclear gene and is transported into the chloroplast. Therefore PAC may be one of the nucleus-encoded factors that function in plastid mRNA maturation and accumulation.
Mol Gen Genet 1998 May
PMID:The PAC protein affects the maturation of specific chloroplast mRNAs in Arabidopsis thaliana. 964 38


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>