PROSITE documentation PDOC00711Deoxyribonuclease I signatures
Deoxyribonuclease I (DNase I) (EC 3.1.21.1) [1] is a vertebrate enzyme which catalyzes the endonucleolytic cleavage of double-stranded DNA to 5'-phosphodinucleotide and 5'-phosphooligonucleotide end-products. DNase I is an enzyme involved in DNA degradation; it is normally secreted outside of the cell but seems to be able to gain access to the nucleus where it is involved in cell death by apoptosis [2].
As shown in the following schematic representation, DNase I is a glycoprotein of about 260 residues with two conserved disulfide bonds.
+-+ +--------+ | | | | xxxxxxxxxxxxxxxxx#xxxxxxCxCxxxxx#xxxxxxxxxCxxxxxxxxCxxxxxxxxxxxxx **** ****
'C': conserved cysteine involved in a disulfide bond. '#': active site residue. '*': position of the patterns.
DNase I has a pH-optimum around 7.5 and requires calcium and magnesium for full activity. It causes single strand nicks in duplex DNA. A proton acceptor-donor chain composed of an histidine and a glutamic acid produce a nucleophilic hydroxyl ion from water, which cleaves the 3'-P-O bond [3]. DNase I is inhibited by actin with which it forms a stoechiometric 1:1 complex [4].
The sequence of DNase I is evolutionary related to that of:
- Human muscle-specific DNase-like protein (gene DNASE1L1 or DNL1L) [5].
- Human protein DHP1 (gene DNASE1L2) [6].
- Human protein DHP2 (gene DNASE1L3) [6].
The first disulfide bond of DNase I is not conserved in the above proteins.
Last update:April 2006 / Pattern revised.
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PROSITE methods (with tools and information) covered by this documentation:
1 | Authors | Suck D. Oefner C. |
Title | Structure of DNase I at 2.0 A resolution suggests a mechanism for binding to and cutting DNA. | |
Source | Nature 321:620-625(1986). | |
PubMed ID | 3713845 |
2 | Authors | Peitsch M.C. Polzar B. Stephan H. Crompton T. MacDonald H.R. Mannherz H.G. Tschopp J. |
Title | Characterization of the endogenous deoxyribonuclease involved in nuclear DNA degradation during apoptosis (programmed cell death). | |
Source | EMBO J. 12:371-377(1993). | |
PubMed ID | 8428592 |
3 | Authors | Suck D. Lahm A. Oefner C. |
Title | Structure refined to 2A of a nicked DNA octanucleotide complex with DNase I. | |
Source | Nature 332:464-468(1988). | |
PubMed ID | 3352748 | |
DOI | 10.1038/332464a0 |
4 | Authors | Kabsch W. Mannherz H.G. Suck D. Pai E.F. Holmes K.C. |
Title | Atomic structure of the actin:DNase I complex. | |
Source | Nature 347:37-44(1990). | |
PubMed ID | 2395459 | |
DOI | 10.1038/347037a0 |
5 | Authors | Parrish J.E. Ciccodicola A. Wehhert M. Cox G.F. Chen E. Nelson D.L. |
Title | A muscle-specific DNase I-like gene in human Xq28. | |
Source | Hum. Mol. Genet. 4:1557-1564(1995). | |
PubMed ID | 8541839 |
6 | Authors | Rodriguez A.M. Rodin D. Nomura H. Morton C.C. Weremowicz S. Schneider M.C. |
Title | Identification, localization, and expression of two novel human genes similar to deoxyribonuclease I. | |
Source | Genomics 42:507-513(1997). | |
PubMed ID | 9205125 |
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