Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.1 (S1 nuclease)
3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The structural organization of the gene coding for human hepatocyte growth factor (hHGF) has been determined by seven overlapping lambda phage genomic clones including three clones that were previously characterized. The gene for hHGF spans about 70 kbp of DNA and consists of 18 exons separated by 17 introns. The coding sequence of hHGF consists of multiple putative domains that are homologous to those observed in plasminogen. These regions were found as separate exons in the gene, and the exon-intron arrangement was similar to that of plasminogen. These results suggest that the genes for hHGF and plasminogen have arisen through gene duplication events from an ancestral gene. The major transcription initiation site of the hHGF gene is located 76 bp upstream of the translational start codon as judged by S1 nuclease mapping and primer extension analyses. A TATA-like element was found 33 nucleotides upstream of the transcription initiation site. Two sequence elements, an interleukin 6 response element (CTGGGA) and a potential binding site for NF-IL6 (TGAGGAAAG), are located near the transcription initiation site. These sequence elements might be involved in the regulation of HGF gene expression.
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PMID:Structural organization and the transcription initiation site of the human hepatocyte growth factor gene. 183 56

Human TNF-stimulated gene 14 (TSG-14) encodes a secreted 42-kDa glycoprotein that shows significant homology to proteins of the pentraxin family, which includes the acute phase reactants C-reactive protein and serum amyloid P component. Levels of TSG-14 protein (also termed PTX-3) become elevated in the serum of mice and humans after injection with bacterial lipopolysaccharide, but in contrast to conventional acute phase proteins, the bulk of TSG-14 synthesis in the intact organism occurs outside the liver. In the present study we cloned and partially sequenced murine genomic TSG-14 DNA. Analysis of the coding region predicts a high degree of amino acid sequence homology between murine and human TSG-14 (88 and 75% identity in the first and second exons, respectively). The promoter of the TSG-14 gene lacks consensus sequences for either a TATA box or CCAAT box. Primer extension analysis and S1 nuclease protection assay revealed one major transcription start site, situated within a consensus sequence for an initiator element. Sequence analysis of a approximately 1.4-kilobase pair fragment of the 5'-flanking region of the TSG-14 gene revealed the presence of numerous potential enhancer binding elements, including six NF-IL6-like sites, four AP-1, one AP-2, one NF-kB, two Sp1, two interferon-gamma-activated sites (GAS), one Hox-1.3, and five binding sites for Ets family members. Transfection of BALB/c 3T3 cells with promoter DNA fragments linked to the luciferase reporter gene revealed that the 5'-flanking region of the TSG-14 gene comprises elements that can mediate a basal level of transcription and inducibility by TNF.
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PMID:Promoter structure and transcriptional activation of the murine TSG-14 gene encoding a tumor necrosis factor/interleukin-1-inducible pentraxin protein. 759 30

A candidate gene for the mouse chromosome 1 host resistance locus Bcg/Ity/Lsh was recently cloned and designated Nramp (natural resistance-associated macrophage protein). Nramp is part of a small family of at least two genes, Nramp1 and Nramp2. Primer extension and cDNA cloning were used to isolate the complete 5' end of the Nramp1 mRNA. Analysis of genomic cosmid and bacteriophage clones overlapping the complete Nramp1 gene revealed that the gene was composed of 15 exons and spanned 11.5 kb of genomic DNA. Positioning of introns on the coding portion of the mRNA revealed a modular relationship between coding exons and predicted structural domains of the protein, with 8 of the 12 transmembrane (TM) domains encoded by individual exons. Northern blotting analysis indicated that Nramp1 expression was restricted to J774A.1 and RAW 264.7 macrophage lines and was dramatically increased by treatment with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). Primer extension and S1 nuclease mapping experiments were used to locate the transcription initiation site of Nramp1 and revealed the presence of one major and several minor initiation sites. Nucleotide sequencing of the corresponding region failed to detect classical TATA and CAAT elements, but identified two putative initiator sequences located near the major initiation site. Consensus sequences for binding of the macrophage and B-cell-specific transcription factor PU.1, as well as several LPS (NF-IL6) and IFN-gamma response elements, were also identified.
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PMID:Genomic structure, promoter sequence, and induction of expression of the mouse Nramp1 gene in macrophages. 766 87

A single human gene, SIAT1, encodes the beta-galactoside alpha 2,6-sialyltransferase from which multiple mRNA isoforms are generated. In rat, expression of the hepatic mRNA isoform (Form 1) has been defined with respect to the transcriptional initiation site and promoter region. We show here that a similar hepatic SIAT1 mRNA isoform exists in human. Another human mRNA isoform, a mature B-cell-specific mRNA isoform (Form 2), was previously reported. Here, we used 5'-RACE and S1 nuclease protection analysis to define the 5'-untranslated region of Form 2 human SIAT1 mRNA. We demonstrate conclusively that Form 2 mRNA is initiated from a point completely distinct from that of Form 1 mRNA. A number of cis-acting regulatory elements residing immediately 5'of the Form 2 initiation site includes AP-1, AP-2, NF-kappa B, NF-IL6, C/EBP, and CREB. A TATAA box is also present 29 bp 5' of the transcriptional initiation site. CAT reporter gene expression from serially-truncated segments of the 5'-flanking region of the Form 2 initiation site indicates that the segment between -784 and +125 was sufficient to promote high level CAT expression in Louckes, a mature B-cell line. The 5'-flanking region to the human Form 1 initiation site is competent in expression of CAT upon transfection of the fusion construct into HepG2, a human hepatoma cell line. Cellular specificity of expression is apparently retained. Louckes cells expressed CAT efficiently from Form 2 promoter but only marginally from the Form 1 promoter. In contrast, CAT expression from Form 1 promoter is more efficient than from the Form 2 promoter in HepG2 cells.
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PMID:Transcription of the beta-galactoside alpha 2,6-sialyltransferase gene in B lymphocytes is directed by a separate and distinct promoter. 872 35

The Fas antigen is a receptor protein transducing cell death signals. Binding of Fas ligands to Fas antigens provokes apoptosis in target cells. Here we report the structure of the promoter of the gene coding for rat Fas antigens. The major transcription start site, identified by the S1 nuclease protection assay, was situated 188 nucleotides upstream of the translational initiation site. The promoter activity was located in the region at the nucleotide position from -142 to -24. In this region we identified a consecutive sequence of NF-kappaB and NF-IL6 consensus sequences, spanning from -142 to -122.
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PMID:Structure of the promoter for the rat Fas antigen gene. 922 46