ID   DNAS1_MOUSE             Reviewed;         284 AA.
AC   P49183; O70532;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   15-JUL-1999, sequence version 2.
DT   24-JAN-2024, entry version 180.
DE   RecName: Full=Deoxyribonuclease-1;
DE            EC=3.1.21.1 {ECO:0000250|UniProtKB:P24855};
DE   AltName: Full=Deoxyribonuclease I;
DE            Short=DNase I;
DE   Flags: Precursor;
GN   Name=Dnase1 {ECO:0000312|MGI:MGI:103157}; Synonyms=Dnl1;
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], AND TISSUE SPECIFICITY.
RC   STRAIN=BALB/cJ; TISSUE=Heart;
RX   PubMed=7857306; DOI=10.1006/bbrc.1995.1153;
RA   Peitsch M.C., Irmler M., French L.E., Tschopp J.;
RT   "Genomic organisation and expression of mouse deoxyribonuclease I.";
RL   Biochem. Biophys. Res. Commun. 207:62-68(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC   STRAIN=BALB/cJ; TISSUE=Kidney, and Parotid gland;
RX   PubMed=9192086; DOI=10.1080/15216549700202441;
RA   Takeshita H., Yasuda T., Nakajima T., Hosomi O., Nakashima Y., Kishi K.;
RT   "Mouse deoxyribonuclease I (DNase I): biochemical and immunological
RT   characterization, cDNA structure and tissue distribution.";
RL   Biochem. Mol. Biol. Int. 42:65-75(1997).
RN   [3]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=10835632; DOI=10.1038/76032;
RA   Napirei M., Karsunky H., Zevnik B., Stephan H., Mannherz H.G., Moeroey T.;
RT   "Features of systemic lupus erythematosus in Dnase1-deficient mice.";
RL   Nat. Genet. 25:177-181(2000).
RN   [4]
RP   TISSUE SPECIFICITY, AND GLYCOSYLATION.
RX   PubMed=15015938; DOI=10.1042/bj20040046;
RA   Napirei M., Ricken A., Eulitz D., Knoop H., Mannherz H.G.;
RT   "Expression pattern of the deoxyribonuclease 1 gene: lessons from the
RT   Dnase1 knockout mouse.";
RL   Biochem. J. 380:929-937(2004).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Kidney;
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).
RN   [6]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=29191910; DOI=10.1126/science.aam8897;
RA   Jimenez-Alcazar M., Rangaswamy C., Panda R., Bitterling J., Simsek Y.J.,
RA   Long A.T., Bilyy R., Krenn V., Renne C., Renne T., Kluge S., Panzer U.,
RA   Mizuta R., Mannherz H.G., Kitamura D., Herrmann M., Napirei M., Fuchs T.A.;
RT   "Host DNases prevent vascular occlusion by neutrophil extracellular
RT   traps.";
RL   Science 358:1202-1206(2017).
CC   -!- FUNCTION: Serum endocuclease secreted into body fluids by a wide
CC       variety of exocrine and endocrine organs (PubMed:29191910). Expressed
CC       by non-hematopoietic tissues and preferentially cleaves protein-free
CC       DNA. Among other functions, seems to be involved in cell death by
CC       apoptosis. Binds specifically to G-actin and blocks actin
CC       polymerization (By similarity). Together with DNASE1L3, plays a key
CC       role in degrading neutrophil extracellular traps (NETs)
CC       (PubMed:29191910). NETs are mainly composed of DNA fibers and are
CC       released by neutrophils to bind pathogens during inflammation
CC       (PubMed:29191910). Degradation of intravascular NETs by DNASE1 and
CC       DNASE1L3 is required to prevent formation of clots that obstruct blood
CC       vessels and cause organ damage following inflammation
CC       (PubMed:29191910). {ECO:0000250|UniProtKB:P00639,
CC       ECO:0000250|UniProtKB:P21704, ECO:0000250|UniProtKB:P24855,
CC       ECO:0000269|PubMed:29191910}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Endonucleolytic cleavage to 5'-phosphodinucleotide and 5'-
CC         phosphooligonucleotide end-products.; EC=3.1.21.1;
CC         Evidence={ECO:0000250|UniProtKB:P24855};
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC         Evidence={ECO:0000250|UniProtKB:P24855};
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:P24855};
CC       Note=Divalent metal cations. Prefers Ca(2+) or Mg(2+).
CC       {ECO:0000250|UniProtKB:P24855};
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P24855}. Zymogen
CC       granule {ECO:0000250|UniProtKB:P24855}. Nucleus envelope
CC       {ECO:0000250|UniProtKB:P24855}. Note=Secretory protein, stored in
CC       zymogen granules and found in the nuclear envelope.
CC       {ECO:0000250|UniProtKB:P24855}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in the parotid and submandibular
CC       gland as well as in the kidney and duodenum (at protein level)
CC       (PubMed:15015938). Expressed at intermediate level in the ileum,
CC       mesenterial lymph nodes, liver, ventral prostate, epididymis, ovary and
CC       stomach (at protein level) (PubMed:15015938). Expressed at low level in
CC       the sublingual, preputial, coagulation and pituitary gland (at protein
CC       level) (PubMed:15015938). Also present in the lachrymal and thyroid
CC       glands, striated muscle, intestine, the urinary bladder and the eye
CC       (PubMed:7857306, PubMed:9192086, PubMed:15015938).
CC       {ECO:0000269|PubMed:15015938, ECO:0000269|PubMed:7857306,
CC       ECO:0000269|PubMed:9192086}.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:15015938}.
CC   -!- DISRUPTION PHENOTYPE: Mice develop symptoms of the autoimmune disease
CC       systemic lupus erythematosus, characterized by high titers of anti-
CC       nuclear autoantibodies (ANA) directed against nucleosomes and double-
CC       stranded DNA, the deposition of immune complexes in glomeruli and full-
CC       blown glomerulonephritis (PubMed:10835632). Mice lacking both Dnase1
CC       and Dnase1l3 show vascular occlusions following bacterial infection:
CC       defects are caused by the formation of intravascular neutrophil
CC       extracellular traps (NETs) clots that obstruct blood vessels and cause
CC       organ damage (PubMed:29191910). {ECO:0000269|PubMed:10835632,
CC       ECO:0000269|PubMed:29191910}.
CC   -!- SIMILARITY: Belongs to the DNase I family. {ECO:0000305}.
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DR   EMBL; U00478; AAA03710.1; -; mRNA.
DR   EMBL; D83038; BAA28622.1; -; mRNA.
DR   CCDS; CCDS27913.1; -.
DR   PIR; JC2526; JC2526.
DR   RefSeq; NP_034191.3; NM_010061.5.
DR   RefSeq; XP_006521837.1; XM_006521774.3.
DR   RefSeq; XP_006521838.1; XM_006521775.3.
DR   RefSeq; XP_006521839.1; XM_006521776.3.
DR   AlphaFoldDB; P49183; -.
DR   SMR; P49183; -.
DR   IntAct; P49183; 1.
DR   STRING; 10090.ENSMUSP00000006136; -.
DR   GlyCosmos; P49183; 2 sites, No reported glycans.
DR   GlyGen; P49183; 2 sites.
DR   iPTMnet; P49183; -.
DR   PhosphoSitePlus; P49183; -.
DR   PaxDb; 10090-ENSMUSP00000006136; -.
DR   ProteomicsDB; 279390; -.
DR   Pumba; P49183; -.
DR   Antibodypedia; 10879; 313 antibodies from 32 providers.
DR   DNASU; 13419; -.
DR   Ensembl; ENSMUST00000006136.11; ENSMUSP00000006136.5; ENSMUSG00000005980.16.
DR   Ensembl; ENSMUST00000120009.8; ENSMUSP00000113119.2; ENSMUSG00000005980.16.
DR   GeneID; 13419; -.
DR   KEGG; mmu:13419; -.
DR   UCSC; uc007xzh.1; mouse.
DR   AGR; MGI:103157; -.
DR   CTD; 1773; -.
DR   MGI; MGI:103157; Dnase1.
DR   VEuPathDB; HostDB:ENSMUSG00000005980; -.
DR   eggNOG; ENOG502QQFT; Eukaryota.
DR   GeneTree; ENSGT00950000182846; -.
DR   HOGENOM; CLU_043335_2_1_1; -.
DR   InParanoid; P49183; -.
DR   OMA; YVTPSHW; -.
DR   OrthoDB; 5396078at2759; -.
DR   PhylomeDB; P49183; -.
DR   TreeFam; TF329541; -.
DR   BRENDA; 3.1.21.1; 3474.
DR   BioGRID-ORCS; 13419; 3 hits in 79 CRISPR screens.
DR   ChiTaRS; Dnase1; mouse.
DR   PRO; PR:P49183; -.
DR   Proteomes; UP000000589; Chromosome 16.
DR   RNAct; P49183; Protein.
DR   Bgee; ENSMUSG00000005980; Expressed in parotid gland and 92 other cell types or tissues.
DR   ExpressionAtlas; P49183; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005635; C:nuclear envelope; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0042588; C:zymogen granule; IEA:UniProtKB-SubCell.
DR   GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR   GO; GO:0004530; F:deoxyribonuclease I activity; IMP:CACAO.
DR   GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR   GO; GO:0004536; F:DNA nuclease activity; ISO:MGI.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0006308; P:DNA catabolic process; IDA:UniProtKB.
DR   GO; GO:0002283; P:neutrophil activation involved in immune response; IDA:UniProtKB.
DR   GO; GO:0002673; P:regulation of acute inflammatory response; IDA:UniProtKB.
DR   GO; GO:0070948; P:regulation of neutrophil mediated cytotoxicity; IDA:UniProtKB.
DR   CDD; cd10282; DNase1; 1.
DR   Gene3D; 3.60.10.10; Endonuclease/exonuclease/phosphatase; 1.
DR   InterPro; IPR018057; Deoxyribonuclease-1_AS.
DR   InterPro; IPR016202; DNase_I.
DR   InterPro; IPR033125; DNASE_I_2.
DR   InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR   InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR   PANTHER; PTHR11371; DEOXYRIBONUCLEASE; 1.
DR   PANTHER; PTHR11371:SF27; DEOXYRIBONUCLEASE-1; 1.
DR   Pfam; PF03372; Exo_endo_phos; 1.
DR   PIRSF; PIRSF000988; DNase_I_euk; 1.
DR   PRINTS; PR00130; DNASEI.
DR   SMART; SM00476; DNaseIc; 1.
DR   SUPFAM; SSF56219; DNase I-like; 1.
DR   PROSITE; PS00919; DNASE_I_1; 1.
DR   PROSITE; PS00918; DNASE_I_2; 1.
DR   Genevisible; P49183; MM.
PE   1: Evidence at protein level;
KW   Actin-binding; Apoptosis; Calcium; Cytoplasmic vesicle; Disulfide bond;
KW   Endonuclease; Glycoprotein; Hydrolase; Nuclease; Nucleus;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000250|UniProtKB:P00639"
FT   CHAIN           23..284
FT                   /note="Deoxyribonuclease-1"
FT                   /id="PRO_0000007278"
FT   ACT_SITE        100
FT                   /evidence="ECO:0000250|UniProtKB:P00639"
FT   ACT_SITE        156
FT                   /evidence="ECO:0000250|UniProtKB:P00639"
FT   SITE            35
FT                   /note="Involved in actin-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P00639"
FT   SITE            87
FT                   /note="Nitration by tetranitromethane destroys a Ca(2+)
FT                   binding site and inactivates enzyme"
FT                   /evidence="ECO:0000250|UniProtKB:P00639"
FT   SITE            89
FT                   /note="Involved in actin-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P00639"
FT   CARBOHYD        40
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        128
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        123..126
FT                   /evidence="ECO:0000250|UniProtKB:P00639"
FT   DISULFID        195..231
FT                   /note="Essential for enzymatic activity"
FT                   /evidence="ECO:0000250|UniProtKB:P00639"
FT   CONFLICT        239..240
FT                   /note="AG -> VR (in Ref. 1; AAA03710)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   284 AA;  32027 MW;  8682E20515EEB510 CRC64;
     MRYTGLMGTL LTLVNLLQLA GTLRIAAFNI RTFGETKMSN ATLSVYFVKI LSRYDIAVIQ
     EVRDSHLVAV GKLLDELNRD KPDTYRYVVS EPLGRKSYKE QYLFVYRPDQ VSILDSYQYD
     DGCEPCGNDT FSREPAIVKF FSPYTEVQEF AIVPLHAAPT EAVSEIDALY DVYLDVWQKW
     GLEDIMFMGD FNAGCSYVTS SQWSSIRLRT SPIFQWLIPD SADTTVTSTH CAYDRIVVAG
     ALLQAAVVPN SAVPFDFQAE YGLSNQLAEA ISDHYPVEVT LRKI
//