Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.22.1 (DNase II)
 429 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acidic endonuclease activity is present in all cells in the body and much of this can be attributed to the previously cloned and ubiquitously expressed deoxyribonuclease II (DNase II). Database analysis revealed the existence of expressed sequence tags and genomic segments coding for a protein with considerable homology to DNase II. This report describes the cloning of this cDNA, which we term deoxyribonuclease IIbeta (DNase IIbeta) and comparison of its expression to that of the originally cloned DNase II (now termed DNase IIalpha). The cDNA encodes a 357 amino acid protein. This protein exhibits extensive homology to DNase IIalpha including an amino-terminal signal peptide and a conserved active site, and has many of the regions of identity that are conserved in homologs in other mammals as well as C. elegans and Drosophila. The gene encoding DNase IIbeta has identical splice sites to DNase IIalpha. Human DNase IIbeta is highly expressed in the salivary gland, and at low levels in trachea, lung, prostate, lymph node, and testis, whereas DNase IIalpha is ubiquitously expressed in all tissues. The expression pattern of human DNase IIbeta suggests that it may function primarily as a secreted enzyme. Human saliva was found to contain DNase IIalpha, but after immunodepletion, considerable acid-active endonuclease remained which we presume is DNase IIbeta. We have localized the gene for human DNase IIbeta to chromosome 1p22.3 adjacent (and in opposing orientation) to the human uricase pseudogene. Interestingly, murine DNase IIbeta is highly expressed in the liver. Uricase is also highly expressed in mouse but not human liver and this may explain the difference in expression patterns between human and mouse DNase IIbeta.
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PMID:The cloning, genomic structure, localization, and expression of human deoxyribonuclease IIbeta. 1137 52

We previously found that a novel DNA endonuclease named DLAD (DNase II-Like Acid DNase) is specifically expressed in murine liver. Here, we describe the isolation and characterization of the human DLAD and mouse Dlad genes. Both DLAD and Dlad consist of 6 exons. DLAD encodes a 361 amino acid protein sharing 34.6% amino acid identity with human DNase II. Although a recombinant protein for the putative human DLAD has a divalent cation-independent acid DNase activity, expression of the DLAD mRNA containing the entire open reading frame was not detected in any human tissues tested, except for lung, in which a short 1.1 kb transcript lacking the first two exons is expressed. Interestingly, sequence analysis of Dlad showed that the 1st exon of the urate oxidase gene, Uox, is located on the opposite strand in its 5'-flanking region. The head-to-head organization of DLAD and UOX is conserved in the human genomic sequence. Promoter analysis revealed that the intergenic region between Dlad and Uox has promoter activity for both the Dlad and Uox directions, however, the corresponding human genomic fragment has promoter activity only for DLAD. It is known that murine Uox is expressed only in the liver, whereas human UOX has been inactivated as a pseudogene. On the basis of these results, the expression of DLAD/Dlad and UOX/Uox is suggested to be coordinated by a common regulatory mechanism(s), and the balance between the two enzymes is thought to be important for maintaining the purine nucleotide pool in the liver.
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PMID:Isolation and characterization of the DLAD/Dlad genes, which lie head-to-head with the genes for urate oxidase. 1170 27