Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An upstream region from the transcription initiation site to -177 base pairs (bp) of the human alpha-cardiac actin gene directs the transient expression of a bacterial chloramphenicol acetyltransferase (CAT) gene only in muscle cells (A. Minty and L. Kedes, Mol. Cell. Biol. 6:2125-2136, 1986). We modified this promoter region by additional 5' deletions, linker-scanning mutations, and insertion-deletion mutations and demonstrated that the asymmetrical sequences in and adjacent to two CArG [for CC(A + T rich)6GG] motifs, located at -140 and -100 bp, play an important positive role in transcription. The significant impairment of transcriptional activity that accompanies the disruption of one CArG box region can be restored by either. This demonstrated that these two elements interact in a mutually dependent and similar manner. Furthermore, a DNA fragment that includes the CArG boxes had significant competitive activity for transcription directed by the alpha-cardiac actin promoter in an in vivo competition assay. We conclude that the two sequences around each CArG box may interact with the same class of trans-acting positive factor(s) and that these interactions may mediate muscle-specific expression. Each of the two CArG regions appears to be bound independently by such a positive factor(s), and the regions support high-level transcription in a synergistic manner. The transcriptional activity of this regulatory region is proportional to its distance from a TATA box (at -30 bp) and is strictly orientation dependent relative to the direction of transcription. Therefore this upstream region is not an enhancer but is a tissue-specific regulatory upstream element.
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PMID:Duplicated CArG box domains have positive and mutually dependent regulatory roles in expression of the human alpha-cardiac actin gene. 2914 7

The defective parvovirus, adeno-associated virus (AAV), contains a single-stranded DNA genome of 4681 bases with inverted terminal repeats of 145 bases. The distal 125 bases of the repeat are palindromic allowing a hairpin to form for initiation of DNA synthesis. The palindromic region contains three palindromes, two smaller internal palindromes flanked by a larger palindrome, which allow the hairpinned DNA to assume a T-shaped conformation during DNA replication. Deletion of an internal palindrome forming one of the crossarms of the T results in the inability of the AAV genome to be rescued from plasmid sequences and replicated. Restoration of the crossarm sequences with DNA that differs in primary sequence but maintains the symmetry of the palindrome results in viable AAV and propagation of the mutant sequences. In this paper we report further studies on the nature of mutants made within the crossarm of the T. Two types of substitution mutants were analyzed. Symmetrical sequence substitution mutants were viable as previously reported. An analysis of the kinetics of AAV DNA accumulation showed that the symmetrical sequence substitution mutants were indistinguishable from wild-type AAV. This was true if the AAV DNA was introduced into the cells either as plasmid DNA or as DNA extracted from virions. In contrast, intermolecular competition experiments showed either a dominance of the wild-type sequence or codominance of both sequences when both alleles were cotransfected into helper virus-infected cells. A preference for the wild-type sequence may also exist but is not required for efficient AAV replication. The second type of mutation studied was an asymmetrical sequence substitution mutant. This mutant was replicated but at a level too low to be propagated. These data suggest that symmetry is required in the internal palindromic region, presumably for the formation of the crossarm structure in the T-shape.
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PMID:Sequence and symmetry requirements within the internal palindromic sequences of the adeno-associated virus terminal repeat. 284 46

The complete sequence for a major Schistosome mansoni eggshell protein gene has been determined from a genomic DNA fragment. The use of an open reading frame encoding a glycine-rich polypeptide was confirmed by in vitro translation of schistosome mRNA in the presence of [3H]glycine and comparison with the amino acid composition of purified, schistosome eggshells. Apart from the extraordinary abundance of glycine and tyrosine which are evenly distributed throughout the polypeptide chain, the most striking features of the deduced amino acid sequence are the presence of five well-conserved tandem repeats of 16-18 residues in the N-terminal region and the asymmetrical distribution of charged residues. Acidic residues (Asp) are confined to the N-terminal region, while basic residues (Lys, His), with the exception of a single histidine, are found in the C-terminal region. A model structure composed of short anti-parallel beta-strands is proposed, in which glycines and residues with small side chains lie within the strands and tyrosines and cysteines are arranged at the bends, where they would be available for cross-linking. Four such strands form one of the tandem repeats which are predicted in turn to form a stack of five closely packed beta-sheets, each of three strands and linked by the more variable fourth strand. The C-terminal region may form a similar but less compact structure. The ordered structure demonstrated by birefringence studies of the schistosome eggshell [Kusel, J. (1970) Parasitology 60, 79-88] could be formed by packing of the polypeptides such that the N-terminal domain contributes counter ions or cross-links to the C-terminal domain of adjacent molecules.
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PMID:Predicted structure of a major Schistosoma mansoni eggshell protein. 291 Dec 80

The genome of malignant rabbit virus (MRV), a newly discovered tumorigenic poxvirus of rabbits, has been analyzed using cloned DNA probes from Shope fibroma virus (SFV) and myxoma virus. Under high stringency conditions for Southern blotting such that SFV probes do not cross-hybridize with myxoma virus DNA, it is demonstrated that greater than 90% of the MRV genome has been derived from myxoma virus, and that approximately 10 kb of SFV-derived sequences have substituted for a similar amount of myxoma sequences. Mapping of the MRV genome indicates that the SFV sequences are present in two regions of the genome, one in each copy of the MRV terminal inverted repeat sequence. Furthermore, fine mapping studies of the integration sites for SFV into the myxoma background show that these SFV sequences are not symmetrical with respect to the left and right genomic termini. At the left end, 4 kb of SFV-derived DNA maps between 6 and 10 kb from the terminus, while at the right end about 5.5 kb of SFV sequences are found to extend at least 1 kb further toward the unique internal sequences. Based on this asymmetrical bipartite distribution of SFV sequences in MRV, a two-stage model to rationalize the origin of MRV is proposed. This model postulates an initial recombination event similar to gene conversion between myxoma and SFV at the right terminus of myxoma, followed by an incomplete transposition of only part of these SFV sequences to the left terminus.
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PMID:Tumorigenic poxviruses: genomic organization of malignant rabbit virus, a recombinant between Shope fibroma virus and myxoma virus. 298 46

A clone overproducing diadenosine tetraphosphatase (diadenosine 5', 5'''-P1, P4-tetraphosphate pyrophosphohydrolase) activity was isolated from an Escherichia coli cosmid library. Localization of the DNA region responsible for stimulation of this activity was achieved by deletion mapping and subcloning in various vectors. Maxicell experiments and immunological assays demonstrated that a 3.5-kilobase-pair DNA fragment carried the structural gene apaH encoding the E. coli diadenosine tetraphosphatase. The DNA coding strand was determined by cloning this fragment in both orientations in pUC plasmids. It was also shown that the overproduction of diadenosine tetraphosphatase decreased the dinucleoside tetraphosphate concentration in E. coli by a factor of 10.
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PMID:Molecular cloning of the Escherichia coli gene for diadenosine 5',5'''-P1,P4-tetraphosphate pyrophosphohydrolase. 299 25

DNA replication in bacteriophage lambda begins at a unique origin between residues 39,000 and 39,200 of the lambda genome. This segment of DNA serves a dual function since it also lies within the coding sequence of the lambda replication initiator protein O which binds origin DNA. The lambda origin sequence contains four 19-base-pair (bp) segments (iterons) which have dyad symmetry, followed by a 40-bp A + T-rich zone of highly asymmetrical base composition. It was noted earlier that lambda origin DNA exhibits an anomalous electrophoretic mobility on gels; that is, the length of DNA as determined by DNA sequencing is approximately 20% less than is predicted from electrophoretic mobility. Recent studies of kinetoplast minicircle DNA (K-DNA) from the protozoan Leishmania tarentolae have led to the proposal that sequence-induced DNA curvature could account for such electrophoretic anomalies by alteration of the shape of the DNA molecule. We now present evidence that the lambda origin contains a static curve.
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PMID:Sequence-induced DNA curvature at the bacteriophage lambda origin of replication. 299 31

Characteristic DNA endonuclease digest fragment electropherograms and restriction site maps permitted differentiation and genome structure analysis of 38 orthopoxviruses that included isolates of monkeypox virus from humans and animals, monkeypox white variants, variola, vaccinia, ectromelia, Tatera (gerbil) and raccoon poxviruses, and cowpox and camelpox viruses. HindIII cleavage sites mapped on the 38 virus genome DNAs plus SmaI, BglI, SacI, KpnI, XhoI, and SalI maps for variola (Harvey) and monkeypox (Copenhagen) virus DNAs were derived essentially by cross-hybridizations with monkeypox, vaccinia, and variola virus-cloned DNA restriction fragments, thus digest fragments could be assigned homologous regions on previously established genome maps. Salient of our observations, the DNA HindIII maps correlated to a high degree, but variations in middle and especially terminal DNA region cleavage sites provided a basis for discerning species, strains and variants. The extent of the inverted terminal repetitions (ITRs) for 37 DNAs were determined with HindIII, PvuI, SalI, and ClaI, plus nine more restriction enzymes for Bangladesh variola virus DNA by hybridizations with either the terminal tandemly repeated 70-bp segment or an EcoRI-PvuI near hairpin-end 75-bp segment from WR vaccinia virus. The opposite terminal regions of variola DNA were considerably asymmetrical compared to the large symmetrical ITRs of the other species examined. An apparent DNA inversion and concurrent deletion (1 kbp) with subsequent repair of DNA to original structure was suggested from right terminal region maps of four viruses chosen from a variola virus passage series in monkeys. Correlative with virus geographic distribution, two strains of monkeypox virus, each containing two variants, were differentiated by DNA profiles of isolates from smallpox-like disease (SLD) patients of the African rainforest region. The DNAs of five monkeypox viruses isolated from laboratory and zoo animals resembled most DNAs from SLD monkeypox viruses from Sierra Leone. A poxvirus from an American raccoon contained 40% DNA that did not cross-hybridize with orthopoxvirus DNA probes. The DNAs of recent isolates from a gerbil and from a camel each mapped as unique African orthopoxvirus species and differed from variola virus.
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PMID:Orthopoxvirus DNA: a comparison of restriction profiles and maps. 299 3

DNA synthesis and adenosine(5')tetraphosphate(5')adenosine (Ap4A) levels decrease in cells treated with EDTA. The inhibitory effect of EDTA can be reversed with micromolar amounts of ZnCl2. ZnCl2 in micromolar concentrations also inhibits Ap4A hydrolase and stimulates amino acid-dependent Ap4A synthesis, suggesting that Zn2+ is modulating intracellular Ap4A pools. Serum addition to G1-arrested cells enhances uptake of Zn, whereas serum depletion leads to a fivefold decrease of the rates of zinc uptake. These results are discussed by regarding Zn2+ as a putative 'second messenger' of mitogenic induction and Ap4A as a possible 'third messenger' and trigger of DNA synthesis.
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PMID:Zinc as a second messenger of mitogenic induction. Effects on diadenosine tetraphosphate (Ap4A) and DNA synthesis. 300 27

The DNA sequences of the diadenosine tetraphosphatase gene (apaH) and of the flanking regions were determined. Three other genes were identified in the flanking regions: ksgA, apaG and folA encoding, respectively, a 16 S rRNA methyltransferase, an unidentified protein of Mr 13,826 and dihydrofolate reductase, with the order folA-apaH-apaG-ksgA. The apaH gene is thus located between folA and ksgA at 1 min on the Escherichia coli chromosome linkage map and folA is transcribed clockwise, whereas ksgA, apaG and apaH are transcribed in the opposite direction. It was shown that ksgA, apaG and apaH can be expressed from a polycistronic mRNA originating from a promoter (p1) located upstream of ksgA. However, another promoter (p2) was found within the ksgA structural gene. This promoter, active in vivo, can account for p1-independent expression of the two distal cistrons, apaG and apaH. Finally, the effect on diadenosine tetraphosphatase over-production of a frameshift mutation causing premature translational termination of apaG suggests that expression of apaG and apaH is coupled at the translational level.
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PMID:The gene for Escherichia coli diadenosine tetraphosphatase is located immediately clockwise to folA and forms an operon with ksgA. 303 29

The nuclear thyroid hormone receptors isolated from cultured human hepatoma cells (Hep G2) were characterized and compared with those from cultured human fibroblasts and rat liver. The Hep G2 nuclear thyroid hormone receptors had an affinity constant (Ka) of 2.1 X 10(10) M-1 and maximal binding capacity (MBC) of 21.0 fmol/100 micrograms DNA for T3 in assays performed on isolated nuclei. 16% of nuclear receptors were released into the media during incubation and had the same Ka. Salt-extracted receptors had a Ka of 1.8 X 10(10) M-1 and MBC of 0.1 pmol/mg protein for T3. Density gradient sedimentation and gel filtration chromatography revealed a sedimentation coefficient of 3.4 S and Stokes radius of 34 A. From these values, a molecular weight of 49,000 and total frictional ratio (f/f0) of 1.4 were calculated, suggesting an asymmetrical shape of the receptor molecule. Heat inactivation occurred with t1/2 of 28.1, 18.0, and 7.9 min at 38, 43, 45 degrees C, respectively. Isoelectric focusing (IEF) of Hep G2 nuclear receptors demonstrated T3 binding proteins at pH 5.3-5.5, 5.7, and 5.9. Evidence that these are nuclear thyroid hormone receptors includes the following: Triiodothyroacetic acid was the most potent competitor of [125I]T3 binding to these proteins followed by L-T3, and L-T4. Cytosolic protein, human serum, and fetal calf serum failed to show the same T3 binding proteins. Ka of these proteins measured by T3 displacement was 1.1-3.2 X 10(9) M-1. Human fibroblast nuclear extract showed similar T3 binding pattern in IEF, except for a slight difference in pI of an acidic band.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thyroid hormone receptors in a human hepatoma cell line: multiple receptor forms on isoelectric focusing. 303 21


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