Cloning and characterization of an actin-resistant DNase I-like endonuclease secreted by macrophages.
We have cloned human and murine DNase I-like cDNAs, termed LS-DNase, which are expressed at high levels in liver and spleen tissues. LS-DNase expression is highly specific to macrophage populations within these and other tissues. Mature LS-DNase from both species is a secreted, non-glycosylated protein containing 285 residues, with a calculated molecular mass of 33 kDa and a basic isoelectric point. Human and murine LS-DNase are highly conserved and share 83% identity. Sequence analysis reveals that LS-DNase shares 46% amino acid sequence identity with DNase I. However, several residues identified as important for interaction of human DNase I with actin are not conserved in both human and murine LS-DNase. Consistent with this observation, recombinant human LS-DNase possesses a DNA hydrolytic activity which, unlike DNase I, is not inhibited by G-actin. The existence of a family of DNase I-like molecules that have tissue-specific expression patterns and the possible role of a macrophage specific DNase are discussed.
Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA. baker.kevin@gene.com
W F
WF
Baron
C Q
CQ
Pan
S A
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Spencer
A M
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Ryan
R A
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Lazarus
K P
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Baker
D000199:Actins / Q000378:metabolism; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers; D003850:Deoxyribonuclease I / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007668:Kidney; D008099:Liver / Q000166:cytology / Q000201:enzymology; D008264:Macrophages / Q000201:enzymology*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013154:Spleen / Q000166:cytology / Q000201:enzymology; D014162:Transfection
D000199:Actins; D017931:DNA Primers; D015345:Oligonucleotide Probes; D011994:Recombinant Proteins; C485421:DNASE1L3 protein, human; C114484:Dnase1l3 protein, mouse; D004706:Endodeoxyribonucleases; D003850:Deoxyribonuclease I