{PDOC00711} {PS00919; DNASE_I_1} {PS00918; DNASE_I_2} {BEGIN} ********************************** * Deoxyribonuclease 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. -Consensus pattern: [LIVM](2)-[AP]-[LQ]-H-[STA]-[STAE]-P-x(5)-E-[LIVM]-[DN]-x- L-x-[DE]-V [H is an active site residue] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Consensus pattern: G-D-F-N-A-x-C-[SAK] [C is involved in a disulfide bond] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: April 2006 / Pattern revised. [ 1] Suck D., Oefner C. "Structure of DNase I at 2.0 A resolution suggests a mechanism for binding to and cutting DNA." Nature 321:620-625(1986). PubMed=3713845 [ 2] Peitsch M.C., Polzar B., Stephan H., Crompton T., MacDonald H.R., Mannherz H.G., Tschopp J. "Characterization of the endogenous deoxyribonuclease involved in nuclear DNA degradation during apoptosis (programmed cell death)." EMBO J. 12:371-377(1993). PubMed=8428592 [ 3] Suck D., Lahm A., Oefner C. "Structure refined to 2A of a nicked DNA octanucleotide complex with DNase I." Nature 332:464-468(1988). PubMed=3352748; DOI=10.1038/332464a0 [ 4] Kabsch W., Mannherz H.G., Suck D., Pai E.F., Holmes K.C. "Atomic structure of the actin:DNase I complex." Nature 347:37-44(1990). PubMed=2395459; DOI=10.1038/347037a0 [ 5] Parrish J.E., Ciccodicola A., Wehhert M., Cox G.F., Chen E., Nelson D.L. "A muscle-specific DNase I-like gene in human Xq28." Hum. Mol. Genet. 4:1557-1564(1995). PubMed=8541839 [ 6] Rodriguez A.M., Rodin D., Nomura H., Morton C.C., Weremowicz S., Schneider M.C. "Identification, localization, and expression of two novel human genes similar to deoxyribonuclease I." Genomics 42:507-513(1997). PubMed=9205125 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}