Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have determined the sequence of the 5'-flanking region and first three exons of the human Na,K-ATPase alpha 1 gene, ATP1A1. Primer extension and S1 nuclease protection analyses of RNA from human kidney, brain, and skeletal muscle indicate that transcription initiates 273 nucleotides upstream of the translation start site. The promoter region contains a potential TATA box at position -27 relative to the transcription initiation site; however, no CCAAT sequence is observed. The 5'-untranslated and 5'-flanking regions are G + C rich. Five sequence elements exhibiting similarity to binding sites for the transcription factor Sp1 are located within the 5'-flanking region. This region also contains potential binding sites for the transcription factors AP-1, AP-2, AP-3, and NF-1, as well as a site which exhibits perfect identity to an 8-bp sequence element important for calcium induction. A comparison of the 5'-flanking region of the alpha 1 and alpha 2 genes reveals differences in potential transcription factor and hormone receptor binding sites which may be important in mediating the tissue- and developmental stage-specific expression of these genes. We have also identified an intragenic DNA probe which detects a restriction fragment length polymorphism at the alpha 1 locus. This marker should facilitate genetic linkage studies designed to evaluate the role of the sodium pump in human disease.
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PMID:The human Na, K-ATPase alpha 1 gene: characterization of the 5'-flanking region and identification of a restriction fragment length polymorphism. 197 Mar 26

The single nuclear gene encoding human ubiquinone-binding protein, a subunit of the cytochrome bc1 complex, was isolated previously (Suzuki, H., Hosokawa, Y., Toda, H., Nishikimi, M., and Ozawa, T. (1989) Biochem. Biophys. Res. Commun. 161, 371-378). The 5'-flanking region contains four putative CCAAT boxes, one putative NF-Y-binding site, and one sequence homologous to the AP-1 recognition site, but lacks typical TATA and GC boxes. Three common nucleotide sequences (5'-TATTCAGGT-3', 5'-ATCTGGCT-3', and 5'-TGGTGA(T/G)AG-3', designated Mt1, Mt3, and Mt4, respectively) were found in the 5'-flanking regions of the genes for human ubiquinone-binding protein and for human cytochrome c1, another subunit of the cytochrome bc1 complex. All three sequences are located in the 280-base pair BamHI-HindIII fragment of the ubiquinone-binding protein gene and in the 154-base pair SalI-PstI fragment of the cytochrome c1 gene. Interestingly, a computer-assisted homology search revealed that the SalI-PstI fragment of the cytochrome c1 gene is related to the long terminal repeat of an endogenous retrovirus. Sequences highly homologous to the three Mt-sequences were also found in the 5'-flanking regions of the genes for the beta subunit of human F0F1-ATPase and rat somatic cytochrome c. The Mt1 sequence (TATT-CAGGT) is similar to the GFII recognition site (RTCACGTG) found in the 5'-flanking regions of the yeast nuclear genes for three cytochrome bc1 complex subunits. Gel retardation assay demonstrated that protein factors in a whole HeLa cell extract bound to both of those fragments. At least three different specific binding sites were thought to exist in the fragments. Specific binding of the protein factors to the sites, possibly to the three Mt sequences, may play an important role in the coordinate regulation of the transcription of nuclear genes encoding subunits responsible for mitochondrial oxidative phosphorylation.
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PMID:Common protein-binding sites in the 5'-flanking regions of human genes for cytochrome c1 and ubiquinone-binding protein. 215 70

Genomic clones containing the 5'-flanking region and exon 1 of the human and rat Na,K-ATPase alpha 3 isoform gene have been isolated and characterized. The nucleotide sequences of 1.6 kb of the rat gene and 2.8 kb of the human gene in the 5'-flanking region were determined. Mapping of transcription initiation sites by primer extension and S1 nuclease protection analyses indicates that transcription is initiated in the same region in both genes although the rat gene has a greater number of initiation sites. Neither gene has a canonical TATA box, having instead a ATAT sequence preceding the transcription initiation sites. There is a perfect CCAAT sequence, in the reverse orientation, approximately 30 bp upstream of the potential TATA box in both genes. We have identified potential binding sites for transcription factors Sp-1, AP-1, AP-2, and AP-4, as well as for glucocorticoid and thyroid hormone receptors in the 5'-flanking regions. These are conserved in both human and rat alpha 3 isoform genes.
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PMID:Characterization of the 5'-flanking region of the human and rat Na,K-ATPase alpha 3 gene. 217 44

We have determined the structure of the gene that encodes the alpha 2 isoform of the human Na,K-ATPase. The gene contains 23 exons and spans approximately 25 kilobases. The amino acid sequence of the human alpha 2 isoform deduced from the genomic sequence exhibits 99% identity to the rat alpha 2 isoform. One of the nine amino acid differences between the human and rat sequences occurs at an amino acid position which is known to be involved in species differences in sensitivity of the alpha 1 isoform to cardiac glycosides. Approximately 1500 base pairs of sequence flanking the 5' end of the alpha 2 gene have been determined. This region contains numerous potential AP-1, AP-2, and NF-1-binding sites, a potential Sp1 recognition site, and several sequences that are similar to the glucocorticoid receptor-binding site. The transcription start site was mapped by primer extension and S1 nuclease protection analyses of RNA from human brain, skeletal muscle, and heart. Multiple transcription initiation sites are clustered between residues -104 to -99 relative to the translation initiation codon. A potential TATA box is located 29 base pairs upstream of the first transcription initiation site. Immediately 5' to the apparent TATA box is a 35-base pair polypurine.polypyrimidine tract containing an imperfect mirror repeat which resembles sequences that form triple-stranded structures. Two intragenic DNA probes which detect restriction fragment length polymorphisms associated with the alpha 2 gene have been identified. These probes will be useful in genetic linkage analyses designed to define the possible role of the Na,K-ATPase in certain hereditary disorders.
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PMID:Characterization of the human Na,K-ATPase alpha 2 gene and identification of intragenic restriction fragment length polymorphisms. 247 73

Changes in intracellular pH (pHin) take part in the mitogenic response. Their importance has been stressed by the finding that mouse fibroblasts expressing a yeast proton pumping ATPase (PMA1) exhibit a transformed phenotype and are tumorigenic. These cells do maintain a higher pHin, supporting the idea that elevated pHin may act as a proliferative trigger. Here we show that cells constitutively expressing PMA1 have higher levels of the AP-1 transcription factor. The use of stable transfectants and transient transfection assays show that PMA1 activity induces transactivation of the c-fos promoter. The activation of the promoter is mediated throughout the serum response element (SRE). The use of protein kinase C inhibitors suggests that AP-1 activation is achieved through a pathway independent of protein kinase C.
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PMID:Activation of the c-fos promoter by increased internal pH. 761 47

Rb represses E2F-mediated transcription in part by blocking the trans-activation domain of E2F. In addition, Rb can convert an E2F binding site from a positive to a negative element. To examine the effect of a Rb-DNA-bound complex on transcription, full-length Rb was fused to the DNA binding domain of GAL4. Here, we report that GAL4-Rb can repress transcription mediated by either Sp1, AP-1, or p53, dependent upon the presence of both the GAL4 DNA binding domain and GAL4 binding sites. Moreover, GAL4-Rb inhibited the activity of the herpes simplex virus tk promoter from GAL4 binding sites located at a distance from the promoter. In contrast, GAL4-Rb was unable to repress basal transcription. Cotransfection of specific cyclins and cyclin-dependent kinases or SV40 T-antigen abolished the repressive activity of GAL4-Rb. The domains of Rb involved in mediating the repression of transcription were mapped to regions that are overlapping, but not identical, to those required for the interaction with E2F. We propose that Rb can function as a general repressor of transcription when bound to the promoter region.
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PMID:The retinoblastoma susceptibility gene product represses transcription when directly bound to the promoter. 772 91

Transcription mechanisms regulating nerve growth factor (NGF) gene expression in the CNS are yet to be thoroughly understood. We have used C6-2B rat glioma cells to characterize the signal transduction pathways that contribute to transcriptional and posttranscriptional regulation of NGF mRNA. Because the NGF promoter contains an AP-1 consensus sequence, we have investigated whether increases in AP-1 binding activity correlate with enhanced NGF mRNA expression. Gel mobility shift assays using an oligonucleotide homologous to the AP-1 responsive element of the rat NGF gene (AP-1NGF) revealed that 12-O-tetradecanoyl phorbol-13-acetate (TPA) and, to a lesser extent, isoproterenol (ISO) and thapsigargin, a microsomal Ca(2+)-ATPase inhibitor, stimulated binding to AP-1NGF within 2 h. All of these stimuli increased NGF mRNA levels within 3 h. Cycloheximide pretreatment blocked the TPA and ISO-mediated binding to AP-1NGF suggesting that de novo synthesis of c-Fos/c-Jun may be required for the transcriptional regulation of NGF gene. Nuclear run-on assays and NGF mRNA decay studies revealed that TPA increases NGF transcription whereas ISO affects both transcription and mRNA stabilization. We propose that (i) different signal transduction mechanisms regulate the expression of the NGF gene in cells derived from the CNS, and (ii) both mRNA transcription and stability account for the cAMP-mediated increase in NGF mRNA levels.
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PMID:Correlation between increased AP-1NGF binding activity and induction of nerve growth factor transcription by multiple signal transduction pathways in C6-2B glioma cells. 871 34

The coat of clathrin-coated vesicles mostly consists of clathrin and adaptor complexes AP-1 or AP-2. Clathrin is released from the vesicles in an ATP-dependent fashion prior to their fusion with endosomes. In the present study we found that ATP strongly inhibits in vitro binding of cytosolic AP-2 to membranes of stripped vesicles, and promotes the release of endogenous AP-2 from clathrin-deprived coated vesicles. Both effects required hydrolysis of ATP. In contrast, binding of AP-1 to stripped vesicles was not affected by ATP, but was enhanced by GTP-gamma-S. These results point to an ATPase that promotes the release of AP-2 from clathrin-coated vesicles.
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PMID:Is an ATPase involved in uncoating of plasma membrane adaptor complex AP-2? 916 94

Recent evidence suggests that c-jun plays a pivotal role in macrophage differentiation induced by multiple agents and that cJun overexpression induces partial macrophage differentiation in the leukemic cell line U-937. The novel differentiating agent bufalin, a Na+/K+ ATPase inhibitor, has also been shown to induce macrophage differentiation in U-937. In order to further define the role of c-jun in macrophage differentiation, we examined the function of c-jun/AP-1 during bufalin induced differentiation in both c-jun transfected and parental U-937 cells. In contrast to phorbol esters, bufalin does not significantly stimulate c-jun or c-fos mRNA expression or AP-1 transactivation. However, bufalin treatment leads to markedly greater morphologic and functional changes indicative of more extensive differentiation in the cJun overexpressing cells compared to the non-transfected controls. Furthermore, cJun overexpressing cells maintain greater viability in the presence of bufalin and arrest in a different phase of the cell cycle than do control cell lines (G0/G1 versus S/G2M, respectively), although some apoptosis occurs in all cell lines treated with bufalin. These data suggest that while bufalin can induce some degree of differentiation in U-937 cells independent of c-jun/AP-1 controlled pathways, the involvement of these pathways by enforced cJun expression enhances the extent of differentiation and shifts the balance between differentiation and apoptosis.
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PMID:Alterations in differentiation and apoptosis induced by bufalin in cJun overexpressing U-937 cells. 945 68

Clathrin and the gamma-adaptin subunit of the AP-1 clathrin adaptor have been previously identified on H-K-ATPase-rich tubulovesicles from gastric acid secretory (oxyntic) cells [C. T. Okamoto, S. M. Karam, Y. Y. Jeng, J. G. Forte, and J. Goldenring. Am. J. Physiol. 274 (Cell Physiol. 43): C1017-C1029]. We further characterized this AP-1 adaptor from rabbit and hog tubulovesicles biochemically and immunologically. Clathrin coat proteins were stripped from purified tubulovesicular membranes and fractionated by hydroxyapatite chromatography. The AP-1 adaptor appears to elute at 200 mM sodium phosphate, based on the presence of proteins in this fraction that are immunoreactive with antibodies against three of the four subunits of this heterotetrameric complex: the gamma-, mu1-, and sigma1-adaptin subunits. Although the putative beta-adaptin subunit in this fraction is not immunoreactive with the anti-beta-adaptin monoclonal antibody (MAb), this beta-adaptin is immunoreactive with polyclonal antibodies (PAbs) directed against the peptide sequence Gly625-Asp-Leu-Leu-Gly-Asp-Leu-Leu-Asn-Leu-Asp-Leu-Gly-Pro-Pro- Val640 , a region conserved between beta1- and beta2-adaptins that is thought to be involved in the binding of clathrin heavy chain. Immunoprecipitation of the AP-1 adaptor complex from this fraction with anti-gamma-adaptin MAb 100/3 resulted in the coimmunoprecipitation of the beta-adaptin that did not react with the anti-beta-adaptin MAb but did react with the anti-beta-adaptin PAbs. In contrast, immunoprecipitation of the AP-1 adaptor complex from crude clathrin-coated vesicles from brain resulted in the coimmunoprecipitation of a beta-adaptin that was recognized by both the anti-beta-adaptin MAb and PAbs. These results suggest that the tubulovesicular AP-1 adaptor complex may be distinct from that found in the trans-Golgi network and may contain an immunologically distinct beta-adaptin. This immunologically distinct beta-adaptin may be diagnostic of apical tubulovesicular endosomes of epithelial cells.
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PMID:An immunologically distinct beta-adaptin on tubulovesicles of gastric oxyntic cells. 981 81


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