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Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The structural organization of an expressed bovine gene (ATPA1) that encodes an isoform of the alpha-subunit of the mitochondrial F0F1 ATP synthase was determined. The gene extends over 10 kilobase-pairs and is divided into 12 exons. The first exon encodes the 5' untranslated region and approximately one-half of the presequence that targets this protein to the mitochondrion. The remainder of the presequence, together with three amino acids of the mature protein, are encoded by exon 2. Primer extension and nuclease protection analyses revealed multiple sites of transcription initiation. The 5' flanking region of the ATPA1 gene can drive the transcription of a reporter gene in an orientation-dependent manner. This promoter region contains several sequence elements which might play an important role in regulating the expression of this gene, including possible TATA and CCAAT boxes, putative Sp1-binding sites, and sequences resembling AP-1, AP-2, AP-4 and cAMP-responsive elements. The ATPA1 gene also contains sequences homologous to several motifs that are shared among some nuclear genes encoding mitochondrial proteins. These include Mt1, Mt3, Mt4, a respiratory enhancer, and NRF-2 sites. Tissue-specific differences in the ATPA1 mRNA levels were observed with high levels found in skeletal muscle and heart, and lower levels in other tissues.
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PMID:Structural organization of a nuclear gene for the alpha-subunit of the bovine mitochondrial ATP synthase complex. 142 Mar 6

The structural organization of the entire human nuclear encoded gene for mitochondrial cytochrome c1 was determined by analyzing a clone obtained from an EMBL3 genomic DNA library. The gene spans 2.4-kilobase pairs and contains seven exons interrupted by six introns of relatively small sizes. All intron/exon splice junctions follow the GT/AG rule. The 5'-flanking region of the gene lacks typical transcriptional regulatory sequence elements such as TATA and CAAT boxes but contains seven putative GC boxes (Sp1 binding sites) and several sequences that resemble another type of the Sp1 responsive element, the enhancer core consensus sequence, the AP-1 responsive element, and the cAMP- and phorbol ester-inducible element. The region also contains a 15-nucleotide sequence highly homologous to the AP-4 consensus sequence and to those in the 5'-flanking regions of the genes for two enzymes associated with respiratory function, the beta subunit of human ATP synthase and chicken 5-aminolevulinate synthase. The presequence, which is essential for the transport of the cytochrome c1 precursor into mitochondria, is encoded in both the first and second exons, and the nucleotide sequence corresponding to the presequence is separated by the first intron. This is the first example of a leader sequence coding for a presequence clearly separated into two parts by an intron.
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PMID:Structural organization of the human mitochondrial cytochrome c1 gene. 253 65

The human heart-skeletal muscle adenine nucleotide translocator (ANT1) gene was isolated and sequenced. It spans 5.8 kilobases and contains four exons. The 5'-nontranscribed region contains typical CCAAT and TATA sequences, a 22-nucleotide pair inverted repeat and a 13-nucleotide pair sequence homologous to a similar region in the ATP synthase beta subunit gene. The region surrounding the first exon and intron is G+C-region surrounding the first exon and intron is G+C-rich, and the intron contains three Sp1 binding motifs. ANT1 was assigned to chromosome 4 using both flow-sorted chromosomes and segregating human-mouse hybrid cells. Additional ANT sequences were found on at least two other chromosomes. ANT1 transcripts were present at high levels in human heart and skeletal muscle but were almost undetectable in liver, kidney, and brain. By contrast, fibroblast ANT (ANT2) mRNAs were present in all five tissues. The unique nature and arrangement of the ANT1 transcriptional control elements may account for this differential expression.
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PMID:A human muscle adenine nucleotide translocator gene has four exons, is located on chromosome 4, and is differentially expressed. 254 78

The gene structure of the human ATP synthase alpha subunit (hATP1) was determined by cloning and sequencing. This gene is approximately 14 kbp in length and contains 12 exons interrupted by 11 introns. Mapping of the clones of hATP1 and Southern blot analysis of the genomic gene showed that there were a single copy of bona fide hATP1 gene and two pseudogenes. Primer extension and S1 mapping analysis showed the presence of multiple transcription initiation sites of the hATP1 gene. No TATA box or CAAT box was found near the transcription initiation sites. Comparison with the bovine gene showed that the 5'-flanking region of the hATP1 gene has an unconserved guanine-cytosine (GC) rich region, including several binding motifs of transcriptional factors, such as Sp1, AP-2, and GCF. By functional assay of gene expression, the basal promoter activity was located near the GC rich region. Comparison of the 5'-upstream region of the hATP1 gene with those of the genes for bovine ATP synthase alpha, human beta, and human gamma subunits indicated three common sequences, suggesting that putative cis-elements coordinate the expressions of the three subunit genes for the ATP synthase. The enhancer activities derived from the 5'-deletion mutants of a hATP1-CAT chimeric gene were different in cell lines from four different human tissues, suggesting the existence of cell type-specific gene regulation.
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PMID:Gene structure and cell type-specific expression of the human ATP synthase alpha subunit. 808 50

To gain insight into the role of the general transcription factor, Sp1, in the expression of nuclear genes involved in mitochondrial biogenesis, we investigated Sp1 activation of the adenine nucleotide translocator 2, cytochrome c1, F1-ATPase beta subunit, and the mitochondria transcription factor (mtTFA) promoters transfected into Drosophila cell lines. The numbers and organization of GC elements vary in the four promoters, but the magnitude of activation by coexpressed human Sp1 was similar. A feature common to the four promoters is the presence of multiple, proximal Sp1-activating elements that account for 50% or more of the transcription activation by Sp1. The distribution and function of individual distal Sp1 elements is less defined and appear to be more promoter-specific. Finally, data from transfected Drosophila cells provide the first direct proof for the involvement of Sp1 in the negative regulation of the ANT2 promoter and as a possible participant in repression of the beta-subunit promoter. The role of Sp1 in both the positive and negative regulation of OXPHOS promoters is unique.
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PMID:On the role of the general transcription factor Sp1 in the activation and repression of diverse mammalian oxidative phosphorylation genes. 1044 39

The GA-binding protein (GABP) is a ubiquitous heteromeric transcription factor implicated in the regulation of several genes involved in mitochondrial energy metabolism including subunits of cytochrome c oxidase, ATP synthase, and mitochondrial transcription factor 1 (mtTF1). GABPalpha subunit binds the PEA3/Ets binding sites (EBS), while GABPbeta contains a transcription activation domain and mediates alphabeta dimer and alpha(2)beta(2) tetramer formation essential for activation of transcription. Here we report the cloning of 2449 bp of the mouse (m) GABPalpha promoter region including 201 bp of the 5' end of the published mGABPalpha cDNA sequence. Surprisingly, sequences homologous to the 5'UTR of mouse, rat and human mitochondrial ATP synthase coupling factor 6 (ATPsynCF6) cDNAs were found165-240 bp upstream of the mGABPalpha cDNA. A search of the non-redundant nucleotide database revealed a human genomic sequence derived from chromosome 21 (21q22) bearing significant homology to the mGABPalpha/ATPsynCF6 promoter region and encompassed the entire hGABPalpha and hATPsynCF6 genes. Primer extension analysis revealed multiple transcription start sites for both mGABPalpha and mATPsynCF6 mRNAs that mapped near the published cDNA 5' ends. Sequence analysis identified several binding sites upstream of the GABPalpha cDNA sequence including sites for GABP (-86, -104, -169, -257, and -994), YY1 (-57), Sp1 (-242 and -226), and NRF1 (-5). No 'TATA' motif was identified near either the GABPalpha or ATPsynCF6 transcription start sites. The human and mouse promoters retain significant sequence identity including binding sites for several tissue-specific transcription factors. Transient transfection assays using Luciferase reporter constructs containing the intergenic region and flanking sequences confirmed that this region of DNA promotes transcription in both directions.
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PMID:Isolation of a bi-directional promoter directing expression of the mouse GABPalpha and ATP synthase coupling factor 6 genes. 1116 19