Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mammalian cells contain two species of glutamine tRNAs, tRNA(CUGGIn) and tRNA(UmUGGIn). The later minor glutamine tRNA which has the UmUG anticodon sequence can recognize an UAG amber termination codon of natural mRNA in an in vitro translation system. Recognition of the UAG nonsense codon by mammalian tRNA(UmUGGIn) is facilitated by two wobble base-pairs at the first and third position of the anticodon. Such unorthodox interaction between the codon and the anticodon which is not in accordance with the wobble hypothesis or the two out of three reading mechanism has been shown only in the recognition of the UAG nonsense codon by natural suppressor tRNA such as yeast tRNA(SGIn) and bovine liver tRNA(CAGLeu). Due to such unique interaction with mRNA, the suppressor activity of mammalian glutamine tRNA(UmUGGIn) is weaker than that of tobacco tRNA(G psi ATyr), which is known to be a natural UAG suppressor tRNA in plants. Retrovirus infection followed by vegetative growth causes the selective and remarkable increase of the amount of UAG suppressor glutamine tRNA(UmUGGIn) in the virus-infected cells. The increased amount of tRNA(UmUGGIn) seems to be important not only for the sufficient production of a viral UAG readthrough protein, but also for the efficient translation of viral mRNAs, since tRNA(UmUGGIn) should read as efficiently the CAA glutamine codon which frequently appears in the viral genome. The increased level of tRNA(UmUGGIn) in virus-infected cells might be due to specific transcription activation of the tRNA gene for tRNA(UmUGGIn). The factor required for the transcription regulation of the suppressor tRNA gene, if it exists in virus infected cells, may not be the same as the factors TFIIIB, IIIC and IIID so far identified. If such a specific transcription factor exists, it would be interesting to characterize it and to elucidate the mechanism by which it is induced by infection with Mo-MuLV or HIV.
 ...
PMID:[Natural UAG suppressor glutamine tRNA in retrovirus infected cells]. 253 81

Cystatin C is an inhibitor of lysosomal cysteine proteases and consists of 120 amino acids. A variant of cystatin C lacking the first NH2-terminal residues and having one amino acid substitution at position 68 forms amyloid deposits mainly in the walls of brain arteries, causing fatal strokes in Icelandic patients with familial cerebral hemorrhage secondary to a form of an autosomal dominant amyloidosis. To understand the molecular basis of the genetic defect, the gene encoding cystatin C was isolated from genomic DNA libraries made from normal tissue and the brain of an Icelandic patient with hereditary cerebral hemorrhage with amyloidosis (HCHWA-I). The data indicate that the cystatin C gene encodes a polypeptide of 146 amino acids, of which the first 26 correspond to a secretory peptide signal sequence. The gene contains two intervening sequences that interrupt the coding region at amino acids 55 and 93. Comparison with genes encoding salivary cystatins and kininogen proteins show sequence homology and conservation of exon-intron structure. Except for a mutation in the second exon (CAG instead of CTG in the normal gene, resulting in the substitution of glutamine for a leucine residue), the gene cloned from the brain of the Icelandic patient is identical to the normal cystatin C gene. Thus, HCHWA-I is the first familial type of amyloidosis related to a point mutation in a gene encoding for an inhibitor. The mutation in the structural gene encoding cystatin C appears to be the primary defect in this inherited disorder causing amyloid fibril formation and accumulation followed by cerebral hemorrhage.
 ...
PMID:Stroke in Icelandic patients with hereditary amyloid angiopathy is related to a mutation in the cystatin C gene, an inhibitor of cysteine proteases. 254 Dec 23

We examined the incidence of point mutation in codons 12, 13 and 61 of c-Ki-ras and N-ras genes in human hepatocellular carcinoma (HCC) using the polymerase chain reaction and oligonucleotide hybridization techniques. Among 34 tissues specimens surgically resected from 30 patients and 5 cell lines of human HCC, only two had ras point mutations; in one case, codon 12 of c-Ki-ras was altered from GGT, coding glycine, to GTT, coding valine; in the other case, codon 61 of N-ras was altered from CAA, coding glutamine, to AAA, coding lysine. Thus, point-mutational activation of ras oncogenes is an uncommon event in human HCC.
 ...
PMID:Low incidence of point mutation of c-Ki-ras and N-ras oncogenes in human hepatocellular carcinoma. 254 5

Human apolipoprotein (apo)-B mRNA undergoes a novel tissue specific editing reaction which replaces a genomically templated cytidine with uridine. This substitution converts codon 2153 from glutamine (CAA) in apo-B100 mRNA to a stop codon (UAA) in apo-B48 mRNA. This novel RNA editing process is responsible for the generation of hepatic apo-B100 and intestinal apo-B48. We have established the following concerning this process: (1) by transfection of a series of deletion mutants into the rat hepatoma cell line McArdle 7777, which makes both apo-B100 and apo-B48, we have defined a minimum sequence of 26 nucleotides that is required for apo-B mRNA editing. The sequence containing the modified nucleotide forms a 26 nucleotide highly conserved stem loop with the modified nucleotide occurring in an 8-base loop. (2) Conversion in vitro of apo-B mRNA has been established, using cell free S100 cytoplasmic extract and synthetic RNA templates. Activity was abolished by protease treatment. (3) Transgenic mice were created which expressed a human apo-B construct spanning the stop codon. Apo-B mRNA was found in all tissues examined and this was shown to undergo editing. (4) In the rat liver, which produces apo B-100 and apo-B48, modulation of the relative proportion of these proteins by thyroxine was demonstrated to be mediated at the level of the RNA editing mechanism. It is concluded that apo-B mRNA is edited by a generally expressed protein and editing is highly regulated.
 ...
PMID:RNA editing: a novel mechanism for regulating lipid transport from the intestine. 260 64

Apolipoprotein (apo) B mRNA undergoes a novel tissue-specific editing reaction, which replaces a genomically templated cytidine with uridine. This substitution converts codon 2153 from glutamine (CAA) in apo B100 mRNA to a stop codon (UAA) in apoB48 mRNA (Powell, L. M., Wallis, S. C., Pease, R. J., Edwards, Y. H., Knott, T. J., and Scott, J. (1987) Cell 50, 831-840). To examine sequences in the human apoB mRNA required for the editing reaction, a series of deletion mutants around the cytidine conversion site was prepared and transfected into a rat hepatoma cell line (McArdle 7777). This cell makes both apoB100 and apoB48. Editing was detected by a primer extension assay on cDNA that had been amplified by the polymerase chain reaction. RNAs of between 2385 and 26 nucleotides spanning the conversion site underwent similar levels of conversion. Editing was confirmed by cloning and sequencing of cDNA corresponding to the transfected RNAs. Conversion did not occur in transfected human hepatoblastoma (HepG2) or epithelial carcinoma (HeLa) cell lines, which do not make apoB48. These results verify that apoB48 is generated by a genuine tissue-specific RNA editing reaction and show that 26 nucleotides of apoB mRNA are sufficient for editing.
 ...
PMID:Sequence requirements for apolipoprotein B RNA editing in transfected rat hepatoma cells. 276 26

A cDNA library was prepared from the poly(A) mRNA isolated from human peripheral blood lymphocytes which were induced by combined treatment with phytohemagglutinin and a phorbol ester. Recombinant plasmids containing human interferon-gamma (HuIFN-gamma) cDNAs were identified by the oligonucleotide-hybridization method. Nucleotide sequence analysis showed that the nucleotide and amino-acid sequences of HuIFN-gamma cDNA in plasmid pIFN gamma-G4 differed from the published data at amino acid position 9 (CAA for glutamine versus AAA for lysine). The cDNA in plasmid pIFN gamma-G4 was expressed under control of the simian virus 40 early promoter in monkey COS cells and a biologically active HuIFN-gamma was secreted from the cells. The cDNA was also inserted into an expression vector carrying an E. coli tryptophan promoter and was expressed in E. coli. The results suggest that the conversion from lysine to glutamine at amino acid position 9 might not affect the specific activity of HuIFN-gamma.
 ...
PMID:Cloning and expression of a novel variant of human interferon-gamma cDNA. 286 Jan 1

The gene-sized macronuclear DNA of the hypotrichous ciliate Stylonychia lemnae contains one size class of DNA molecules of 1.85 kb (1 kb = 10(3) base-pairs) coding for beta-tubulin. These DNA molecules consist of two different beta-tubulin genes, beta 1 and beta 2, which are amplified to about 150,000 (beta 1) and 30,000 (beta 2) copies per macronucleus. Both genes were cloned and sequenced entirely. The coding sequences of the two molecules (1329 base-pairs including TGA) predict identical amino acid sequences for the proteins and show a nucleotide homology of 97.2%. The nucleotide as well as the encoded amino acid sequences are highly conserved, when compared to beta-tubulin genes from vertebrates. The ciliate-specific codon TAA specifying glutamine is present only in the beta 2-tubulin gene, whereas glutamine is encoded soley by CAA in the beta 1-tubulin gene. The 5' and 3'-non-coding regions of both beta-tubulin genes are similar in length, but differ extremely in nucleotide sequence. Both beta-tubulin genes are transcriptionally active in S. lemnae, although not all putative transcription-regulatory sequences known from higher eukaryotes can be detected within the non-coding regions. The two transcription products localized by S1-mapping experiments show a similar length of about 1.40 kb and transcription seems to be regulated differently for beta 1 and beta 2.
 ...
PMID:Nucleotide sequence and expression of two beta-tubulin genes in Stylonychia lemnae. 312 2

A transforming N-ras allele was molecularly cloned from the RD human rhabdomyosarcoma cell line, and the nature of its activation studied. Construction of chimeric recombinants between the RD-transforming allele and a normal human allele enabled us to localize the alteration responsible for the activation to the second exon of the N-ras gene. The nucleotide sequence of this exon, when compared to that of the normal allele, revealed a single difference at the 61st amino acid position of the encoded protein; the CAA codon for glutamine in the normal allele was mutated to a CAT codon for histidine in the RD-transforming allele. This result is the first description of a histidine replacing glutamine in the 61st position and provides further evidence that the 61st amino acid is one of the preferential sites for N-ras activation.
 ...
PMID:N-ras gene activation in the RD human rhabdomyosarcoma cell line. 315 13

A Batak Indonesian from North Sumatra with hemoglobin (Hb) D Punjab (alpha 2 beta 2 121----Gln) and hemoglobin Constant Spring (Hb CoSp) is described. The 24-year-old man did not have clinical symptoms, and his hematological indices were normal. However, he had a persistent slight elevation of fetal hemoglobin level. His mother and his brother were heterozygous for Hb D Punjab; his father had Hb CoSp trait. A sister did not have any abnormal hemoglobin. To show the exact molecular defect leading to the synthesis of Hb CoSp in this family, genomic DNA from the father was analyzed by hybridization with synthetic oligonucleotides. Genomic DNA was digested with Sst I and Hind III producing a 1.05-kb fragment from the 3' end segment of the alpha 2-globin gene, including the termination codon. Two nonadecamers were synthesized to serve as probes: one, entirely homologous to the normal 3' end of alpha 2A-globin gene sequence, including the termination codon TAA, the other different from it by a replacement of the T in the termination codon TAA with C, changing it to CAA, the codon for the amino acid glutamine. DNA from normal controls gave a positive signal with the normal alpha 2TAA oligonucleotide probe but negative with the alpha 2 CAA probe. The father of propositus who had Hb CoSp trait gave a positive signal with the normal alpha 2TAA oligonucleotide probe as well as with the alpha 2CAA oligonucleotide probe, showing him to be heterozygous for the alpha 2CAA-globin gene. This result shows that the Hb CoSp in the Batak family is indeed due to a replacement of T by C in the TAA termination codon of the alpha 2-globin gene changing it to CAA the condon for glutamine. This explains the resulting readthrough of the untranslated sequence of the mRNA.
 ...
PMID:Hemoglobin constant spring defined by specific oligonucleotide hybridization and hemoglobin D Punjab (beta 121----Gln) in a Batak Indonesian family. 317 65

Several genes for surface antigens of the Paramecium aurelia complex of species have been isolated. In addition to known deletions of the 51A gene, we have obtained deletions involving the 51B gene and have developed a procedure for obtaining deletions of additional genes. Both Mendelian and non-Mendelian deletions of both the A and B genes have been found. In the non-Mendelian deletions the genes are present in the micronuclei and absent in the macronuclei. Processing of micronuclear DNA into new macronuclear DNA at conjugation and autogamy is under the control of the old macronucleus, and newly forming macronuclei become exactly like the old. Thus in the non-Mendelian mutants, macronuclei have a specific antigen gene deleted and also are impaired in their ability to direct normal DNA processing at the next conjugation or autogamy. These cases, along with others, show that this system of macronuclear control is a fundamental feature of ciliate genetics. The sequence of the 51A and 51C genes is described and compared with the 156G and 51H genes obtained by others. The 51A and 156G genes are remarkably similar while 51C and 51H are rather different. No introns or pseudogenes have been observed. Some, possibly all, of the genes are on the ends of chromosomes. Characteristic upstream and downstream sequences adjacent to the coding portions of the genes are given. The sequences UAA and UAG are preferred over CAA and CAG for glutamine while UGA is the true stop codon.
 ...
PMID:Molecular biology of the genes for immobilization antigens in Paramecium. 332 80


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