ID   DNAS1_RABIT             Reviewed;         281 AA.
AC   O18998;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   25-MAY-2022, entry version 119.
DE   RecName: Full=Deoxyribonuclease-1;
DE            EC=3.1.21.1 {ECO:0000269|PubMed:9230129};
DE   AltName: Full=Deoxyribonuclease I;
DE            Short=DNase I;
DE   Flags: Precursor;
GN   Name=DNASE1; Synonyms=DNL1;
OS   Oryctolagus cuniculus (Rabbit).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX   NCBI_TaxID=9986;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 22-41, FUNCTION, CATALYTIC
RP   ACTIVITY, AND GLYCOSYLATION AT ASN-39.
RC   STRAIN=Japanese white; TISSUE=Pancreas, and Urine;
RX   PubMed=9230129; DOI=10.1042/bj3250465;
RA   Yasuda T., Takeshita H., Nakajima T., Hosomi O., Nakashima Y., Kishi K.;
RT   "Rabbit DNase I: purification from urine, immunological and proteochemical
RT   characterization, nucleotide sequence, expression in tissues, relationships
RT   with other mammalian DNases I and phylogenetic analysis.";
RL   Biochem. J. 325:465-473(1997).
CC   -!- FUNCTION: Serum endocuclease secreted into body fluids by a wide
CC       variety of exocrine and endocrine organs (PubMed:9230129). Expressed by
CC       non-hematopoietic tissues and preferentially cleaves protein-free DNA
CC       (By similarity). Among other functions, seems to be involved in cell
CC       death by apoptosis. Binds specifically to G-actin and blocks actin
CC       polymerization (PubMed:9230129). Preferentially attacks double-stranded
CC       DNA and produces oligonucleotides with 5'-phospho and 3'-hydroxy
CC       termini (PubMed:9230129). Together with DNASE1L3, plays a key role in
CC       degrading neutrophil extracellular traps (NETs) (By similarity). NETs
CC       are mainly composed of DNA fibers and are released by neutrophils to
CC       bind pathogens during inflammation (By similarity). Degradation of
CC       intravascular NETs by DNASE1 and DNASE1L3 is required to prevent
CC       formation of clots that obstruct blood vessels and cause organ damage
CC       following inflammation (By similarity). {ECO:0000250|UniProtKB:P21704,
CC       ECO:0000250|UniProtKB:P49183, ECO:0000269|PubMed:9230129}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Endonucleolytic cleavage to 5'-phosphodinucleotide and 5'-
CC         phosphooligonucleotide end-products.; EC=3.1.21.1;
CC         Evidence={ECO:0000269|PubMed:9230129};
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: Equivalent levels in pancreas and parotid gland,
CC       low amounts in kidney, liver, small intestine, stomach and thymus.
CC       {ECO:0000269|PubMed:9230129}.
CC   -!- SIMILARITY: Belongs to the DNase I family. {ECO:0000305}.
CC   -!- CAUTION: It is uncertain whether Met-1 or Met-5 is the initiator.
CC       {ECO:0000305}.
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DR   EMBL; D82875; BAA21724.1; -; mRNA.
DR   RefSeq; NP_001076209.1; NM_001082740.1.
DR   AlphaFoldDB; O18998; -.
DR   SMR; O18998; -.
DR   STRING; 9986.ENSOCUP00000009746; -.
DR   iPTMnet; O18998; -.
DR   PRIDE; O18998; -.
DR   GeneID; 100009513; -.
DR   KEGG; ocu:100009513; -.
DR   CTD; 1773; -.
DR   eggNOG; ENOG502QQFT; Eukaryota.
DR   InParanoid; O18998; -.
DR   OrthoDB; 1282784at2759; -.
DR   Proteomes; UP000001811; Unplaced.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005635; C:nuclear envelope; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-EC.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0000737; P:DNA catabolic process, endonucleolytic; ISS:UniProtKB.
DR   GO; GO:0002283; P:neutrophil activation involved in immune response; ISS:UniProtKB.
DR   GO; GO:0002673; P:regulation of acute inflammatory response; ISS:UniProtKB.
DR   GO; GO:0070948; P:regulation of neutrophil mediated cytotoxicity; ISS:UniProtKB.
DR   Gene3D; 3.60.10.10; -; 1.
DR   InterPro; IPR018057; Deoxyribonuclease-1_AS.
DR   InterPro; IPR016202; DNase_I.
DR   InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR   InterPro; IPR005135; Endo/exonuclease/phosphatase.
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; SSF56219; 1.
DR   PROSITE; PS00919; DNASE_I_1; 1.
PE   1: Evidence at protein level;
KW   Actin-binding; Apoptosis; Calcium; Cytoplasmic vesicle;
KW   Direct protein sequencing; Disulfide bond; Endonuclease; Glycoprotein;
KW   Hydrolase; Nuclease; Nucleus; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000269|PubMed:9230129"
FT   CHAIN           22..281
FT                   /note="Deoxyribonuclease-1"
FT                   /id="PRO_0000007280"
FT   ACT_SITE        99
FT                   /evidence="ECO:0000250|UniProtKB:P00639"
FT   ACT_SITE        155
FT                   /evidence="ECO:0000250|UniProtKB:P00639"
FT   SITE            34
FT                   /note="Involved in actin-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P00639"
FT   CARBOHYD        39
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:9230129"
FT   DISULFID        122..125
FT                   /evidence="ECO:0000250|UniProtKB:P00639"
SQ   SEQUENCE   281 AA;  31346 MW;  6B6535FCE1FE29E8 CRC64;
     MRSEMLTALL TLAVLLQVAG SLKIAAFNIR SFGETKMSNA TLTSYIVRIL QRYDIALIQE
     VRDSHLTAVG KLLDKLNEKA ADTYRFVASE PLGRRTYKER YLFVYRPDQV SVLDSYYYDD
     GCEPCGTDTF SREPAVVRFS SPSTKVREFA IVPLHSAPED AVAEIDALYD VYLDVQKKWG
     LQDVMLMGDF NADYSYVTSS QWSSIRLRTN PAFKWLIPDT ADTTATSTNC AYDRIVVAGP
     LLQDAVVPNS AAPFNFQAAY GLSNQLAQAI SDHYPVEVTL A