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

The temperate phage phi C31 is the most studied bacteriophage infecting Streptomyces spp., and has been used to develop an extensive and widely used series of cloning vectors. The sequence of 10 kb of phi C31 DNA containing most or all of the essential early genes was determined. Among the ORFs, 14 (perhaps 15) appear to be protein-coding, and these have been designated ORF1 to ORF14 and ORFX. Previously mapped transcripts appear to initiate upstream from ORFs 1, 8, 11 and 12, and within ORF3 and ORF12, in each case close to one example of the unusual ('21-mer') sequences that appear to serve as a recognition site for RNA polymerase early in the phi C31 lytic cycle [Ingham et al., Mol. Microbiol. 9 (1993) 1267-1274]. Further copies of the 21-mer are upstream from ORF2 and ORF13. There are four recognisable examples of a conserved inverted repeat sequence motif (CIR) thought to bind phi C31 repressor [Smith and Owen, Mol. Microbiol. 5 (1991) 2833-2844]. Only one CIR is closely associated with a 21-mer sequence, though three are located between known transcription units. Of all 14 ORFs, only one (ORF11) would encode a protein unmistakably resembling other known proteins; its product appears to be a DNA polymerase. Strikingly, two codons, TTA (Leu) and AGG (Arg), are absent from the 14 ORFs.
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PMID:Sequence of the essential early region of phi C31, a temperate phage of Streptomyces spp. with unusual features in its lytic development. 808 46

A single-base substitution in the coding region of the androgen receptor (AR) gene caused complete androgen insensitivity in a patient with 46,XY karyotype. The mutation was a T-to-G transition in exon 6 and changed the codon 807 from ATG (methionine) to AGG (arginine) in the hormone-binding domain of the protein. The mutation was inserted into the wild-type human AR cDNA and the resulting cDNA expressed in CV-1 cells. Native and mutated AR proteins synthesized in recipient cells had identical molecular masses. Ligand-binding activity of the mutant receptor was less than 5% of that of the wild-type AR. The mutant's interaction with an androgen-response element in vitro was identical to that of the native aporeceptor; however, it did not transactivate a reporter gene construct in transfected CV-1 cells. Androgen insensitivity in our patient was thus due to altered structure of the receptor's steroid-binding region, which prevented the mutated AR from gaining a transcriptionally active form in vivo.
Hum Mol Genet 1993 Nov
PMID:A single-base substitution in exon 6 of the androgen receptor gene causing complete androgen insensitivity: the mutated receptor fails to transactivate but binds to DNA in vitro. 828 Nov 40

A 1.2-kb DNA fragment of the cytochrome oxidase subunit I (CO I) gene of mitochondria isolated from an ascidian, Halocynthia roretzi, was amplified by polymerase chain reaction (PCR) and sequenced. Codons AGA and AGG appeared in its reading frame, indicating that these are sense codons in this organelle. Sequence comparisons with the corresponding regions of other animal mitochondrial CO I genes suggest that codons AGA and AGG correspond to glycine in the ascidian mitochondrial genome, but not to serine as in most invertebrate genomes, nor to stops as in vertebrate genomes. The other codons are identical to those of vertebrate mitochondria.
J Mol Evol 1993 Jan
PMID:Codons AGA and AGG are read as glycine in ascidian mitochondria. 838 78

The crystal structure of the DNA decamer d(AGGCATGCCT) has been determined to a resolution of 1.3 A and R factor of 13.9%. The structure has a unique conformation with each of the decamer single strands forming base-pairing interactions with two symmetry-related strands. The central eight bases of the decamer form an A-DNA octamer duplex with one symmetry-related strand whilst the terminal 5'-A and T-3' bases are flipped out and away from the octamer helix axis to form base-pairing interactions with a second symmetry-related strand. These A.T base-pairs lie perpendicular to the crystallographic c axis and pack within the unit cell in conjunction with a symmetry-related A.T base-pair displaced by 3.4 A degrees along the c axis. A novel base triplet interaction of the type A*(G.C) is present in the structure with interaction from the major groove side of the terminal 5'-A base to the minor groove of the central A-DNA octamer. This structure reports the first example of cobalt hexammine binding to a right-handed DNA duplex. The crystallographic asymmetric unit contains two cobalt hexammine ligands with one site in the major groove coordinating via hydrogen bonds to the 5'-AGG bases, and the second site located between DNA molecules and interacting with the oxygen atoms of phosphate groups.
J Mol Biol 1996 Feb 23
PMID:The high resolution crystal structure of the DNA decamer d(AGGCATGCCT). 859 1

Both sequence length and sequence content are important parameters in determining stability of the fragile X syndrome CGG repeat. In order to estimate the incidence of uninterrupted CGG repeats in the general population and to gain insight into mechanisms responsible for the loss and acquisition of AGG interruptions, 406 randomly selected FMR1 CGG repeat alleles from four broad ethnic groups were assayed for AGG punctuation. Among the 79 different classes of alleles detected, long uninterrupted tracts of pure repeats were rare in the general population, with only 1/406 or 0.25% found at the instability threshold (34-37 pure CGG repeats). There was no significant difference (P>0.05) in the distribution of alleles with long (>20) pure repeat tracts among the different ethnic groups, suggesting that different ethnic groups should be equally susceptible to the development of the disease. Analysis of an additional 43 alleles with total repeat lengths between 35 and 50 repeats, revealed that highly interrupted CGG repeats alleles (>2 AGG interruptions) occur preferentially at modal repeat lengths in the population, providing confirmatory evidence that the presence of AGG interruptions confers stability. A consideration of length variation of the most 3' tract of pure repeats revealed a bimodal distribution pattern with maxima at approximately 10 and 20 repeats. Only unimodal distributions with maxima 9 or 10 were observed for the 5' tract and middle CGG tract within the FMR1 CGG repeat substructure. These results suggest that the loss of the most 3' AGG interruption or its conversion to CGG is a common event in the human population, occurring by a mechanism which preserves overall repeat length. This bias for loss of the distal-most AGG interruption likely plays an important part in predisposing human alleles to the development of the X syndrome.
Hum Mol Genet 1995 Dec
PMID:Population survey of the human FMR1 CGG repeat substructure suggests biased polarity for the loss of AGG interruptions. 863 88

Lambda's int gene contains an anomalously high frequency of the rare arginine codons AGA and AGG when compared to genes of Escherichia coli or to the rest of phage lambda. These are the least frequent codons in genes of E. coli and are recognized by the rarest tRNAs. The presence of these codons reduces the translation rate and, depending on the context, this can strongly modulate translational efficiency by a variety of mechanisms. In this study, we show that expression of the natural int gene may also be modulated by rare arginine codon usage, and we explore this mechanism.
Mol Microbiol 1996 Jul
PMID:Modulation of lambda integrase synthesis by rare arginine tRNA. 884 35

There are two types of transcripts for the human A1, adenosine receptor. They are expressed in a tissue-specific manner in human tissues and contain distinct exons. Previously, it had appeared that the two transcripts may have occurred through alternative splicing. The transcript beta has two upstream AUG codons, which in transiently transfected COS-7 cells leads to a reduced level of receptor expression. When genomic sequence including sequences 5' to transcriptional start site, exon 1A, intron 1A, exon 1B, intron 1B, exon 2, and coding sequence was inserted into an expression vector (pCMV5/huA1), the resulting transcripts had the same overall structure as the transcripts present in human tissues. Primer extension and 5' rapid amplification of cDNA ends of mRNA from transfected cells revealed the transcription start sites for these two transcripts occurred in what previously had been termed introns. These results were confirmed with similar analysis of mRNA derived from human tissues. Two nonconsensus putative TATA boxes (TTAAGA and TTTAAA) are located upstream of the transcription start sites for transcripts alpha and beta. When the TATA boxes and their flanking sequences were fused to a firefly luciferase gene containing promoterless vector, both demonstrated strong promoter activity in Chinese hamster ovary cells. Promoter A directs the synthesis of transcript alpha, and promoter B directs the synthesis of transcript beta. Promoter A contains a series of AGG elements between the putative TATA box and the transcription start, which accounts for a major portion of the promoter activity based on deletion and mutation analysis. In general, promoter A is more active than promoter B in transfected cells. The nonconsensus TATA box in promoter B plays a more important role in promoter activity than the TATA box in promoter A. The human A1 adenosine receptor gene appears to use two separate promoters to direct synthesis of distinct transcripts, which can then regulate the relative abundance of A1 adenosine receptor in tissues. We have redefined the human A1 adenosine receptor gene structure based on these new data.
Mol Pharmacol 1995 Dec
PMID:Separate promoters in the human A1 adenosine receptor gene direct the synthesis of distinct messenger RNAs that regulate receptor abundance. 884 13

To understand the origins of the fragile X syndrome and factors predisposing alleles to instability and hyperexpansion, we have compared the haplotype (using markers FRAXAC1, FRAXAC2, and DXS548) and AGG interspersion patterns of the FMR1 CGG repeat for 214 normal and 16 premutation chromosomes. Association testing between interspersion pattern and haplotype reveals a highly significant (P < 0.002) non-random distribution, indicating that all three markers are useful in phylogenetic reconstruction of mutational change. Parsimony analysis of the FMR1 CGG repeat substructure predicts that loss of AGG interruptions has occurred independently on many haplotypes associated with the fragile X syndrome, partially explaining the haplotype diversity of this disease. Among haplotypes found in linkage disequilibrium with the fragile X mutation, two different modes of mutation and predisposition to instability have been identified. One pathway has involved the frequent and recurrent loss of AGG interruptions from rare asymmetrical ancestral array structures. Intergenerational transmission studies suggest that these predisposed chromosomes progress relatively rapidly to the disease state. In contrast, the second mutational pathway involves a single haplotype which has maintained two AGG interruptions. Parsimony analysis of CGG repeat substructure within this haplotype suggests that larger alleles have been generated by gradual increments of CGG repeats distal to the most 3' interruption. Pedigree analysis of the intergenerational stability of alleles of this haplotype confirms a gradual progression toward instability thresholds. As a result, a large reservoir of chromosomes carrying large repeats on this haplotype exists. These chromosomes are predisposed to disease. The present data support a model in which there are at least two different mutational pathways predisposing alleles to instability and hyperexpansion associated with the fragile X syndrome.
Hum Mol Genet 1996 Mar
PMID:Haplotype and interspersion analysis of the FMR1 CGG repeat identifies two different mutational pathways for the origin of the fragile X syndrome. 885 55

In a genetic selection designed to isolate Escherichia coli mutations that increase expression of the IS 10 transposase gene (tnp), we unexpectedly obtained viable mutants defective in translation initiation factor 3 (IF3). Several lines of evidence led us to conclude that transposase expression, per se, was not increased. Rather, these mutations appear to increase expression of the tnp'-'lacZ gene fusions used in this screen, by increasing translation initiation at downstream, atypical initiation codons. To test this hypothesis we undertook a systematic analysis of start codon requirements and measured the effects of IF3 mutations on initiation from various start codons. Beginning with an efficient translation initiation site, we varied the AUG start codon to all possible codons that differed from AUG by one nucleotide. These potential start codons fall into distinct classes with regard to translation efficiency in vivo: Class I codons (AUG, GUG, and UUG) support efficient translation; Class IIA codons (CUG, AUU, AUC, AUA, and ACG) support translation at levels only 1-3% that of AUG; and Class IIB codons (AGG and AAG) permit levels of translation too low for reliable quantification, importantly, the IF3 mutations had no effect on translation from Class I codons, but they increased translation from Class II codons 3-5-fold, and this same effect was seen in other gene contexts. Therefore, IF3 is generally able to discriminate between efficient and inefficient codons in vivo, consistent with earlier in vitro observations. We discuss these observations as they relate to IF3 autoregulation and the mechanism of IF3 function.
Mol Microbiol 1996 Jul
PMID:Escherichia coli translation initiation factor 3 discriminates the initiation codon in vivo. 885 89

We identified four families in which we suspected the presence of genetic factors predisposing them to cancer. We examined one family with features suggesting Li-Fraumeni syndrome for the presence of a germline p53 mutation in 13 of its members. To detect germline p53 mutations we performed polymerase chain reaction/nonradioisotopic single-strand conformation polymorphism and DNA sequencing analysis on exons 4-9 of the p53 gene. Mutated polymerase chain reaction-restriction fragment length polymorphism analysis was also performed on exon 5 to confirm the mutation identified by the sequencing analysis. A novel germline p53 mutation was identified at codon 133 (ATG-->AGG) in exon 5, resulting in the substitution of arginine for methionine, in all four cancer-affected individuals and in three apparently healthy individuals. We also analyzed tumor specimens for additional p53 mutations in the wild-type alleles using the same methods. However, heterozygosity was retained, and no other additional mutations in the wild-type allele were identified in any of the tumor tissues. It is possible that additional mutations in the wild-type allele are not always necessary for the loss of tumor suppressor functions. This study presents serious clinical and ethical problems about the predictive value of identifying germline p53 mutations in presymptomatic carriers. However, accurate predictive testing will be very useful in identifying unaffected individuals who are at increased risk of developing cancer and in detecting cancer at an early stage.
J Mol Med (Berl) 1997 Jan
PMID:Germline p53 mutation at codon 133 in a cancer-prone family. 902 Mar 84


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