DNS2A_MOUSE
ID DNS2A_MOUSE Reviewed; 353 AA.
AC P56542; O55053;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Deoxyribonuclease-2-alpha;
DE EC=3.1.22.1;
DE AltName: Full=Acid DNase;
DE AltName: Full=Deoxyribonuclease II alpha;
DE Short=DNase II alpha;
DE AltName: Full=Lysosomal DNase II;
DE Flags: Precursor;
GN Name=Dnase2; Synonyms=Dnase2a, Dnl2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9714827; DOI=10.1016/s0378-1119(98)00280-7;
RA Baker K.P., Baron W.F., Henzel W.J., Spencer S.A.;
RT "Molecular cloning and characterization of human and murine DNase II.";
RL Gene 215:281-289(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10903447; DOI=10.1016/s0378-1119(00)00209-2;
RA Krieser R.J., Eastman A.;
RT "Deoxyribonuclease II: structure and chromosomal localization of the murine
RT gene, and comparison with the genomic structure of the human and three C.
RT elegans homologs.";
RL Gene 252:155-162(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, AND INVOLVEMENT IN FATAL ANEMIA.
RX PubMed=11375492; DOI=10.1126/science.292.5521.1546;
RA Kawane K., Fukuyama H., Kondoh G., Takeda J., Ohsawa Y., Uchiyama Y.,
RA Nagata S.;
RT "Requirement of DNase II for definitive erythropoiesis in the mouse fetal
RT liver.";
RL Science 292:1546-1549(2001).
RN [5]
RP FUNCTION, AND INVOLVEMENT IN PERINATAL LETHALITY.
RX PubMed=12181746; DOI=10.1038/sj.cdd.4401056;
RA Krieser R.J., MacLea K.S., Longnecker D.S., Fields J.L., Fiering S.,
RA Eastman A.;
RT "Deoxyribonuclease IIalpha is required during the phagocytic phase of
RT apoptosis and its loss causes perinatal lethality.";
RL Cell Death Differ. 9:956-962(2002).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Hydrolyzes DNA under acidic conditions with a preference for
CC double-stranded DNA. Plays a major role in the degradation of nuclear
CC DNA in cellular apoptosis during development. Necessary for proper
CC fetal development and for definitive erythropoiesis in fetal liver,
CC where it degrades nuclear DNA expelled from erythroid precursor cells.
CC {ECO:0000269|PubMed:11375492, ECO:0000269|PubMed:12181746}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Endonucleolytic cleavage to nucleoside 3'-phosphates and 3'-
CC phosphooligonucleotide end-products.; EC=3.1.22.1;
CC -!- SUBCELLULAR LOCATION: Lysosome.
CC -!- TISSUE SPECIFICITY: Highly expressed in fetal liver macrophages.
CC {ECO:0000269|PubMed:11375492}.
CC -!- DISEASE: Note=Absence of Dnase2 is a cause of severe fetal anemia and
CC of perinatal lethality due to malformation of the diaphragm.
CC {ECO:0000269|PubMed:11375492, ECO:0000269|PubMed:12181746}.
CC -!- MISCELLANEOUS: Not required for the generation of the characteristic
CC DNA fragmentation observed in apoptotic cells, but for the degradation
CC of DNA from dying cells.
CC -!- SIMILARITY: Belongs to the DNase II family. {ECO:0000305}.
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DR EMBL; AF045741; AAC35750.1; -; mRNA.
DR EMBL; AF190459; AAF20386.1; -; Genomic_DNA.
DR EMBL; BC058609; AAH58609.1; -; mRNA.
DR EMBL; BC060661; AAH60661.1; -; mRNA.
DR CCDS; CCDS22484.1; -.
DR RefSeq; NP_034192.1; NM_010062.3.
DR AlphaFoldDB; P56542; -.
DR SMR; P56542; -.
DR BioGRID; 199253; 7.
DR STRING; 10090.ENSMUSP00000003910; -.
DR GlyGen; P56542; 4 sites.
DR iPTMnet; P56542; -.
DR PhosphoSitePlus; P56542; -.
DR PaxDb; P56542; -.
DR PeptideAtlas; P56542; -.
DR PRIDE; P56542; -.
DR Antibodypedia; 13408; 230 antibodies from 32 providers.
DR Ensembl; ENSMUST00000003910; ENSMUSP00000003910; ENSMUSG00000003812.
DR GeneID; 13423; -.
DR KEGG; mmu:13423; -.
DR UCSC; uc009moa.1; mouse.
DR CTD; 13423; -.
DR MGI; MGI:1329019; Dnase2a.
DR VEuPathDB; HostDB:ENSMUSG00000003812; -.
DR eggNOG; KOG3825; Eukaryota.
DR GeneTree; ENSGT00390000002634; -.
DR HOGENOM; CLU_053867_0_0_1; -.
DR InParanoid; P56542; -.
DR OMA; ILYNDQK; -.
DR OrthoDB; 605654at2759; -.
DR PhylomeDB; P56542; -.
DR TreeFam; TF314536; -.
DR BRENDA; 3.1.22.1; 3474.
DR Reactome; R-MMU-432720; Lysosome Vesicle Biogenesis.
DR BioGRID-ORCS; 13423; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Dnase2a; mouse.
DR PRO; PR:P56542; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P56542; protein.
DR Bgee; ENSMUSG00000003812; Expressed in lip and 112 other tissues.
DR ExpressionAtlas; P56542; baseline and differential.
DR GO; GO:0005764; C:lysosome; TAS:MGI.
DR GO; GO:0004531; F:deoxyribonuclease II activity; IDA:MGI.
DR GO; GO:0004520; F:endodeoxyribonuclease activity; ISO:MGI.
DR GO; GO:0006309; P:apoptotic DNA fragmentation; IBA:GO_Central.
DR GO; GO:0006308; P:DNA catabolic process; IMP:MGI.
DR GO; GO:0000737; P:DNA catabolic process, endonucleolytic; IMP:MGI.
DR GO; GO:0043353; P:enucleate erythrocyte differentiation; IMP:MGI.
DR GO; GO:0050776; P:regulation of immune response; IGI:MGI.
DR InterPro; IPR004947; DNase_II.
DR PANTHER; PTHR10858; PTHR10858; 1.
DR Pfam; PF03265; DNase_II; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Developmental protein; Disulfide bond; Endonuclease;
KW Glycoprotein; Hydrolase; Lysosome; Nuclease; Reference proteome; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..353
FT /note="Deoxyribonuclease-2-alpha"
FT /id="PRO_0000007292"
FT ACT_SITE 297
FT /evidence="ECO:0000250"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 214
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 268
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT DISULFID 22..161
FT /evidence="ECO:0000255"
FT DISULFID 269..349
FT /evidence="ECO:0000255"
FT DISULFID 310..329
FT /evidence="ECO:0000255"
SQ SEQUENCE 353 AA; 38811 MW; F53CDD81CF6FFCF4 CRC64;
MATLRSLLLA ALLWVPAEAL SCYGDSGQPV DWFVVYKLPA HSGSRDTPKG LTYKYMDQNS
DGWQDGVGYI NSSEGAVGRS LQPLYRKNSS QLAFLLYNDQ PPKSSSARDS TGHGHTKGVL
LLDQEGGFWL VHSVPRFPPP ASSGAYTWPP NAQTFGQTLL CVSLPFTQFA RIGKQLTYTY
PLVYDHKLEG FFAQKLPDLE TVIKNQHVLH EPWNSSVILT SQAGATFQSF AKFGKFGDDL
YSGWLAEALG TNLQVQFWQN SPGILPSNCS GAYQVLDVTQ TGFPGPSRLT FSATEDHSKW
CVAPQGPWAC VGDMNRNKAE THRGGGTVCT QLPSFWKAFQ SLVKDWKPCI EGS
