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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein tyrosine phosphatases (PTPs) are comprised of two superfamilies, the phosphatase I superfamily containing a single low-molecular-weight PTP (lmwPTP) family and the phosphatase II superfamily including both the higher-molecular-weight PTP (hmwPTP) and the dual-specificity phosphatase (DSP) families. The phosphatase I and II superfamilies are often considered to be the result of convergent evolution. The PTP sequence and structure analyses indicate that lmwPTPs, hmwPTPs, and DSPs share similar structures, functions, and a common signature motif, although they have low sequence identities and a different order of active sites in sequence or a circular permutation. The results of this work suggest that lmwPTPs and hmwPTPs/DSPs are remotely related in evolution. The earliest ancestral gene of PTPs could be from a short fragment containing about 90 approximately 120 nucleotides or 30 approximately 40 residues; however, a probable full PTP ancestral gene contained one transcript unit with two lmwPTP genes. All three PTP families may have resulted from a common ancestral gene by a series of duplications, fusions, and circular permutations. The circular permutation in PTPs is caused by a reading frame difference, which is similar to that in DNA methyltransferases. Nevertheless, the evolutionary mechanism of circular permutation in PTP genes seems to be more complicated than that in DNA methyltransferase genes. Both mechanisms in PTPs and DNA methyltransferases can be used to explain how some protein families and superfamilies came to be formed by circular permutations during molecular evolution.
Mol Biol Evol 2003 May
PMID:Different protein tyrosine phosphatase superfamilies resulting from different gene reading frames. 1267 37

Various transcription factors, such as Sp1 and MAZ, include C2H2-type zinc-finger motifs and are able to bind to GC-rich cis-elements that are distributed in the promoter regions of numerous mammalian genes. The consensus sequence of Sp1-binding sites is very similar to that of MAZ-binding sites. In fact, Sp1 and MAZ bind to the same cis-elements in the promoters of the genes for the receptor for serotonin 1A (HT1Ar), endothelial nitric-oxide synthase (eNOS), phenylethanolamine N-methyltransferase (PNMT), the receptor for parathyroid hormone (PTHr), MAZ and the major late promoter of adenovirus (AdMLP). It appears that two consecutive zinc-finger motifs of Sp1 and MAZ might be essential for the interaction of each protein with DNA. Sp1 and MAZ activated the expression of the genes for HT1Ar and PTHr, as well as AdMLP. Both Sp1 and MAZ inhibited the expression of the gene for MAZ, while expression of the gene for eNOS was enhanced by Sp1 and repressed by MAZ. These observations suggest that both Sp1 and MAZ might have dual functions in the regulation of gene expression. Our results suggest, furthermore, that histone deacetylases are involved in autorepression of the gene for MAZ, while expression of DNA methyltransferase I is associated with suppression of the expression of the gene for MAZ by Sp1. Thus, both deacetylation and methylation might be involved in the regulation of expression of individual genes, with different zinc-finger proteins binding to the same cis-elements but recruiting different proteins, such as methylases and acetylases, to the transcriptional complex.
Int J Mol Med 2003 May
PMID:Transcriptional regulation by zinc-finger proteins Sp1 and MAZ involves interactions with the same cis-elements. 1268 88

The human T-lymphoid cell line H9 resistant to 3'-azido-2',3'-dideoxythymidine (AZT) has a very low level of thymidine kinase (TK) expression which accounts for the failure of AZT to inhibit HIV-1 replication. In the present study DNA methylation and histone deacetylation as possible mechanisms of decreased TK gene expression in the resistant cells were investigated. The resistant cells expressed high levels of DNA methyltransferases (DNMTs) 3a and 3b. The DNA methylation inhibitor, 5-aza-cytidine (5-aza-C), increased TK gene expression and antiviral activity of AZT in the resistant cells, while histone deacetylase inhibitor trichostatin A (TSA) had no effect. The results suggest that hypermethylation of the TK gene but not histone deacetylation in AZT-resistant H9 cells accounts for decreased TK gene expression and failure of AZT to inhibit HIV-1 replication probably due to overexpression of DNMT 3a and 3b.
Int J Mol Med 2003 Jun
PMID:The mechanism of 3'-azido-2',3'-dideoxythymidine resistance to human lymphoid cells. 1273 16

Co-transfections of reporter plasmids and plasmids encoding the catalytic domain of the murine Dnmt3a DNA methyltransferase lead to inhibition of reporter gene expression. As Dnmt3a mutants with C-->A and E-->A exchanges in the conserved PCQ and ENV motifs in the catalytic center of the enzyme also cause repression, we checked for their catalytic activity in vitro. Surprisingly, the activity of the cysteine variant and of the corresponding full-length Dnmt3a variant is only two to sixfold reduced with respect to wild-type Dnmt3a. In contrast, enzyme variants carrying E-->A, E-->D or E-->Q exchanges of the ENV glutamate are catalytically almost inactive, demonstrating that this residue has a central function in catalysis. Since the glutamic acid residue contacts the flipped base, its main function could be to hold the target base at a position that supports methyl group transfer. Whereas wild-type Dnmt3a and the ENV variants form covalent complexes with 5-fluorocytidine modified DNA, the PCN variant does not. Therefore, covalent complex formation is not essential in the reaction mechanism of Dnmt3a. We propose that correct positioning of the flipped base and the cofactor and binding to the transition state of methyl group transfer are the most important roles of the Dnmt3a enzyme in the catalytic cycle of methyl group transfer.
J Mol Biol 2003 Jun 13
PMID:Catalytic mechanism of DNA-(cytosine-C5)-methyltransferases revisited: covalent intermediate formation is not essential for methyl group transfer by the murine Dnmt3a enzyme. 1278 69

The PWWP domain is a ubiquitous eukaryotic protein module characterised by a region of sequence similarity of approximately 80 amino acids containing a highly conserved PWWP motif. It is frequently found in proteins associated with chromatin. We have determined the structure of a PWWP domain from the S. pombe protein SPBC215.07c using NMR spectroscopy. The structure is composed of a five stranded beta barrel followed by two alpha helices. Comparison to the recently reported structure of a homologous domain from the mammalian DNA methyltransferase Dnmt3b reveals substantial differences both in the C-terminal helical region and in the PWWP motif.
J Mol Biol 2003 Jul 11
PMID:Structural variation in PWWP domains. 1284 72

The technique of representational difference analysis (RDA) was originally described by Lisitsyn et al. (1993) as a means of identifying differences between complex genomes by the use of subtractive hybridisation (1). This protocol for methylation-sensitive RDA (Me-RDA) describes adaptations to the original technique that, by the use of oligonucleotides for HpaII or Hin6I sites, allow the identification of sequences whose methylation differs between two sources of DNA. Differences in the methylation of the maternal and paternal alleles of imprinted genes have been described for most imprinted genes studied to date (2). The importance of methylation in the control of imprinted gene expression has been clearly demonstrated by the perturbation of allelic expression in mice deficient in Dnmt1, the major mammalian DNA methyltransferase (3), and methylation has been suggested to fulfill the necessary requirements of an "imprint" (4).
Methods Mol Biol 2001
PMID:Identification of imprinted loci by methylation: use of methylation-sensitive representational difference analysis (Me-RDA). 1284 45

Lyon has proposed that long interspersed nuclear element 1 (LINE-1 or L1) repeats may be mediators for the spread of X chromosome inactivation. Cells from ICF patients who are deficient in one of the DNA methyltransferases, DNMT3B, provide an opportunity to explore and refine this hypothesis. Southern blot and bisulfite methylation analyses indicate that, in normal somatic cells, X-linked L1s are hypermethylated on both the active and inactive X chromosomes. In contrast, ICF syndrome cells with DNMT3B mutations have L1s that are hypomethylated on the inactive X, but not on the active X or autosomes. The DNMT3B methyltransferase, therefore, is required for methylation of L1 CpG islands on the inactive X, whereas methylation of the corresponding L1 loci on the active X, as well as most autosomal L1s, is accomplished by another DNA methyltransferase. This unique phenomenon of identical allelic modifications by different enzymes has not been previously observed. Apart from CpG island methylation, the ICF inactive X is basically normal in that it forms a Barr body, is associated with XIST RNA, mostly replicates late, and its X-inactivated genes are mostly silent. Because the unmethylated state of the ICF inactive X L1s probably reflects their methylation status at the time of X inactivation, these data suggest that unmethylated L1 elements, but not methylated L1s, may have a role in the spreading of X chromosome inactivation.
Hum Mol Genet 2003 Oct 01
PMID:X inactivation-specific methylation of LINE-1 elements by DNMT3B: implications for the Lyon repeat hypothesis. 1292 68

The nucleotide sequence was established for the full-length Flavobacterium aquatile operon coding for the FauI restriction-modification system. The operon is unusual in structure and has the gene order control protein gene-DNA methyltransferase A gene-restriction endonuclease gene-DNA methyltransferase B gene, other than in the known analogs. The genes are similarly oriented and overlap. On evidence of sequence analysis, both methyltransferases are C5 enzymes, the control protein is similar to that of other restriction-modification systems, and restriction endonuclease is low-homologous to other enzymes cleaving the DNA upper strand in position 4 or 5 relative to the recognition site.
Mol Biol (Mosk)
PMID:[The unique FauI restriction-modification system: cloning and comparative analysis of protein structure]. 1294 34

The early region 2a (E2a) of adenovirus type 2 (Ad2) DNA codes for a 72,000-dalton DNA-binding protein and is expressed in the Ad2-transformed hamster cell line HE1 but not in cell lines HE2 and HE3 (H. Esche, J. Virol. 41:1076-1082, 1982; K. Johansson et al., J. Virol. 27:628-639, 1978). An inverse correlation between DNA methylation at the 5'-CCGG-3' sites of the E2a region and of gene expression in these cell lines has been observed (L. Vardimon et al., Nucleic Acids Res. 8:2461-2473, 1980). When the cloned E2a region of Ad2 DNA is methylated in vitro at the 5'-CCGG-3' sites, the gene is not transcribed after being injected into the nuclei of Xenopus laevis oocytes, whereas unmethylated DNA is expressed (L. Vardimon et al., Eur. J. Cell Biol. 25:13-15, 1981; L. Vardimon et al., Proc. Natl. Acad. Sci. U.S.A. 79:1073-1077, 1982). These data demonstrate that DNA methylation is directly involved in the shut-off of transcription. In the present communication we investigated in detail the control region of the gene for the DNA-binding protein in Ad2-transformed cell lines and showed that the first late control region (map coordinate 72 on the viral DNA) of the E2a region is present in its entirety in cell lines HE1, HE2, and HE3. The HaeIII sites (5'-GGCC-3') in the E2a region in all three cell lines were not methylated. When the DNA methyltransferase BsuRI was used, all 5'-GGCC-3' sites in the cloned E2a region of Ad2 DNA were methylated in vitro. It was shown that methylation of these sites did not inhibit the expression of this viral gene in X. laevis oocytes. Thus, for methylation to affect gene expression in the E2a region it has to occur at specific sites (e.g., 5'-CCGG-3') which may be different for other genes.
Mol Cell Biol 1982 Dec
PMID:In vitro methylation of the BsuRI (5'-GGCC-3') sites in the E2a region of adenovirus type 2 DNA does not affect expression in Xenopus laevis oocytes. 1458 98

DNA duplexes containing a single phosphoryldisulfide link in place of the natural internucleotide phosphodiester bond were employed in affinity modification of Cys142 in cytosine-C5 DNA methyltransferase SsoII (M.SsoII). The possibility of duplex-M.SsoII conjugation as a result of disulfide exchange was demonstrated. The crosslinking efficiency proved to depend on the DNA primary structure, modification position, and the presence of S-adenosyl-L-homocysteine, a nonreactive analog of the methylation cofactor. The SH group of M.SsoII Cys142 was assumed to be close to the DNA sugar-phosphate backbone in the DNA-enzyme complex.
Mol Biol (Mosk)
PMID:[Covalent binding of Cys142 from SsoII methyltransferase with DNA duplexes, containing a phosphoryldisulfide internucleotide group]. 1459 29


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