ID DNAS1_BOVIN Reviewed; 282 AA. AC P00639; A5PK44; Q8MJ27; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 15-DEC-1998, sequence version 3. DT 02-SEP-2026, entry version 205. DE RecName: Full=Deoxyribonuclease-1; DE EC=3.1.21.1 {ECO:0000269|PubMed:3352748, ECO:0000269|PubMed:4976790, ECO:0000269|PubMed:5166750}; DE AltName: Full=Deoxyribonuclease I; DE Short=DNase I; DE Flags: Precursor; GN Name=DNASE1; Synonyms=DNL1; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Pancreas; RX PubMed=9469931; DOI=10.1016/s0378-1119(97)00582-9; RA Chen C.Y., Lu S.C., Liao T.H.; RT "Cloning, sequencing and expression of a cDNA encoding bovine pancreatic RT deoxyribonuclease I in Escherichia coli: purification and characterization RT of the recombinant enzyme."; RL Gene 206:181-184(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=14680812; DOI=10.1016/j.bbrc.2003.10.161; RA De Maria A., Arruti C.; RT "Bovine DNase I: gene organization, mRNA expression, and changes in the RT topological distribution of the protein during apoptosis in lens epithelial RT cells."; RL Biochem. Biophys. Res. Commun. 312:634-641(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Hereford; TISSUE=Fetal pancreas; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases. RN [4] RP PROTEIN SEQUENCE OF 23-260. RX PubMed=4734471; DOI=10.1016/s0021-9258(19)44326-3; RA Liao T.-H., Salnikow J., Moore S., Stein W.H.; RT "Bovine pancreatic deoxyribonuclease A. Isolation of cyanogen bromide RT peptides; complete covalent structure of the polypeptide chain."; RL J. Biol. Chem. 248:1489-1495(1973). RN [5] RP ERRATUM OF PUBMED:4734471, AND SEQUENCE REVISION. RX PubMed=1348510; DOI=10.1016/s0021-9258(18)42607-5; RA Liao T.-H., Salnikow J., Moore S., Stein W.H.; RL J. Biol. Chem. 267:7957-7957(1992). RN [6] RP VARIANT ALLELE C/D PRO-143. RX PubMed=4735137; DOI=10.1016/s0021-9258(19)44218-x; RA Salnikow J., Murphy D.; RT "Bovine pancreatic deoxyribonucleases A and C. A proline for histidine RT substitution in deoxyribonuclease C."; RL J. Biol. Chem. 248:1499-1501(1973). RN [7] RP VARIANT ALLELE C/D PRO-143. RX PubMed=4856650; DOI=10.1016/s0021-9258(19)42737-3; RA Liao T.-H.; RT "Bovine pancreatic deoxyribonuclease D."; RL J. Biol. Chem. 249:2354-2356(1974). RN [8] RP ACTIVE SITE HIS-156, FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR. RX PubMed=4976790; DOI=10.1016/s0021-9258(18)91874-0; RA Price P.A., Moore S., Stein W.H.; RT "Alkylation of a histidine residue at the active site of bovine pancreatic RT deoxyribonuclease."; RL J. Biol. Chem. 244:924-928(1969). RN [9] RP ACTIVE SITE TYR-87, FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR. RX PubMed=5166750; DOI=10.1016/s0021-9258(19)45871-7; RA Hugli T.E., Stein W.H.; RT "Involvement of a tyrosine residue in the activity of bovine pancreatic RT deoxyribonuclease A."; RL J. Biol. Chem. 246:7191-7200(1971). RN [10] RP X-RAY CRYSTALLOGRAPHY (2 ANGSTROMS), AND DISULFIDE BONDS. RX PubMed=3713845; DOI=10.1038/321620a0; RA Suck D., Oefner C.; RT "Structure of DNase I at 2.0-A resolution suggests a mechanism for binding RT to and cutting DNA."; RL Nature 321:620-625(1986). RN [11] RP X-RAY CRYSTALLOGRAPHY (2 ANGSTROMS), AND GLYCOSYLATION AT ASN-40. RX PubMed=3560229; DOI=10.1016/0022-2836(86)90280-9; RA Oefner C., Suck D.; RT "Crystallographic refinement and structure of DNase I at 2-A resolution."; RL J. Mol. Biol. 192:605-632(1986). RN [12] RP X-RAY CRYSTALLOGRAPHY (2 ANGSTROMS) WITH NICKED DNA OCTANUCLEOTIDE, RP COFACTOR, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=3352748; DOI=10.1038/332464a0; RA Suck D., Lahm A., Oefner C.; RT "Structure refined to 2 A of a nicked DNA octanucleotide complex with DNase RT I."; RL Nature 332:464-468(1988). RN [13] RP X-RAY CRYSTALLOGRAPHY (2 ANGSTROMS), AND GLYCOSYLATION AT ASN-40. RX PubMed=1748997; DOI=10.1016/0022-2836(91)90502-w; RA Lahm A., Suck D.; RT "DNase I-induced DNA conformation. 2-A structure of a DNase I-octamer RT complex."; RL J. Mol. Biol. 222:645-667(1991). RN [14] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS). RX PubMed=1518054; DOI=10.1016/0022-2836(92)91064-v; RA Weston S.A., Lahm A., Suck D.; RT "X-ray structure of the DNase I-d(GGTATACC)2 complex at 2.3-A resolution."; RL J. Mol. Biol. 226:1237-1256(1992). RN [15] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF COMPLEX WITH ACTIN, AND ACTIVE RP SITE. RX PubMed=2395459; DOI=10.1038/347037a0; RA Kabsch W., Mannherz H.G., Suck D., Pai E.F., Holmes K.C.; RT "Atomic structure of the actin:DNase I complex."; RL Nature 347:37-44(1990). CC -!- FUNCTION: Serum endocuclease secreted into body fluids by a wide CC variety of exocrine and endocrine organs (PubMed:2395459, CC PubMed:3352748, PubMed:4976790, PubMed:5166750). Expressed by non- CC hematopoietic tissues and preferentially cleaves protein-free DNA (By CC similarity). Among other functions, seems to be involved in cell death CC by apoptosis (PubMed:2395459). Binds specifically to G-actin and blocks CC actin polymerization (PubMed:2395459). Together with DNASE1L3, plays a CC key role in degrading neutrophil extracellular traps (NETs) (By CC similarity). NETs are mainly composed of DNA fibers and are released by CC neutrophils to bind pathogens during inflammation (By similarity). CC Degradation of intravascular NETs by DNASE1 and DNASE1L3 is required to CC prevent formation of clots that obstruct blood vessels and cause organ CC damage following inflammation (By similarity). CC {ECO:0000250|UniProtKB:P21704, ECO:0000250|UniProtKB:P49183, CC ECO:0000269|PubMed:2395459, ECO:0000269|PubMed:3352748, CC ECO:0000269|PubMed:4976790, ECO:0000269|PubMed:5166750}. 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:3352748, ECO:0000269|PubMed:4976790, CC ECO:0000269|PubMed:5166750}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:3352748, ECO:0000269|PubMed:4976790, CC ECO:0000269|PubMed:5166750}; CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:3352748, ECO:0000269|PubMed:4976790, CC ECO:0000269|PubMed:5166750}; CC Note=Divalent metal cations. Prefers Ca(2+) or Mg(2+). CC {ECO:0000269|PubMed:3352748, ECO:0000269|PubMed:4976790, CC ECO:0000269|PubMed:5166750}; CC -!- INTERACTION: CC P00639; P68135: ACTA1; Xeno; NbExp=3; IntAct=EBI-8545986, EBI-367540; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:4734471}. Zymogen CC granule {ECO:0000305}. Nucleus envelope {ECO:0000250|UniProtKB:P24855}. CC Note=Secretory protein, stored in zymogen granules and found in the CC nuclear envelope. {ECO:0000250|UniProtKB:P24855}. CC -!- PTM: The only differences between the A and B forms and the C and D CC forms are in the compositions of the carbohydrate bound to Asn-40. CC {ECO:0000269|PubMed:1748997}. CC -!- SIMILARITY: Belongs to the DNase I family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ001538; CAA04819.1; -; mRNA. DR EMBL; AF528509; AAM93248.1; -; Genomic_DNA. DR EMBL; BC142349; AAI42350.1; -; mRNA. DR PIR; JC6532; NDBOA. DR RefSeq; NP_776959.1; NM_174534.2. DR RefSeq; XP_024840423.1; XM_024984655.2. DR RefSeq; XP_024840425.1; XM_024984657.2. DR RefSeq; XP_024840426.1; XM_024984658.2. DR RefSeq; XP_024840427.1; XM_024984659.2. DR RefSeq; XP_059737140.1; XM_059881157.1. DR RefSeq; XP_059737141.1; XM_059881158.1. DR PDB; 1ATN; X-ray; 2.80 A; D=23-282. DR PDB; 1DNK; X-ray; 2.30 A; A=23-282. DR PDB; 2A3Z; X-ray; 2.08 A; B=23-282. DR PDB; 2A40; X-ray; 1.80 A; B/E=23-282. DR PDB; 2A41; X-ray; 2.60 A; B=23-282. DR PDB; 2A42; X-ray; 1.85 A; B=23-282. DR PDB; 2D1K; X-ray; 2.50 A; B=23-282. DR PDB; 2DNJ; X-ray; 2.00 A; A=23-282. DR PDB; 3CJC; X-ray; 3.90 A; D=23-282. DR PDB; 3DNI; X-ray; 2.00 A; A=23-282. DR PDB; 3W3D; X-ray; 1.80 A; B=23-282. DR PDB; 7NXV; X-ray; 2.55 A; B/F=23-282. DR PDB; 7NZM; EM; 3.96 A; D=23-282. DR PDB; 9FJU; EM; 3.84 A; E/F=1-282. DR PDB; 9FJY; EM; 3.79 A; E/F=1-282. DR PDB; 9NB9; EM; 3.03 A; E=1-282. DR AlphaFoldDB; P00639; -. DR EMDB; EMD-12665; -. DR EMDB; EMD-49223; -. DR EMDB; EMD-50516; -. DR EMDB; EMD-50517; -. DR PCDDB; P00639; -. DR SMR; P00639; -. DR DIP; DIP-541N; -. DR FunCoup; P00639; 286. DR IntAct; P00639; 2. DR MINT; P00639; -. DR STRING; 9913.ENSBTAP00000026784; -. DR BindingDB; P00639; -. DR ChEMBL; CHEMBL5712; -. DR GlyCosmos; P00639; 1 site, No reported glycans. DR GlyGen; P00639; 1 site. DR iPTMnet; P00639; -. DR PaxDb; 9913-ENSBTAP00000026784; -. DR GeneID; 282217; -. DR KEGG; bta:282217; -. DR CTD; 1773; -. DR VEuPathDB; HostDB:ENSBTAG00000020107; -. DR VGNC; VGNC:28132; DNASE1. DR eggNOG; ENOG502QQFT; Eukaryota. DR HOGENOM; CLU_043335_2_1_1; -. DR InParanoid; P00639; -. DR OMA; YHFVVSE; -. DR OrthoDB; 10061407at2759; -. DR BRENDA; 3.1.21.1; 908. DR EvolutionaryTrace; P00639; -. DR PRO; PR:P00639; -. DR Proteomes; UP000009136; Chromosome 25. DR Bgee; ENSBTAG00000020107; Expressed in adult mammalian kidney and 102 other cell types or tissues. DR GO; GO:0005576; C:extracellular region; EXP:UniProtKB. DR GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0042588; C:zymogen granule; IEA:UniProtKB-SubCell. DR GO; GO:0004530; F:deoxyribonuclease I activity; EXP:UniProtKB. DR GO; GO:0003677; F:DNA binding; IBA:GO_Central. DR GO; GO:0006308; P:DNA catabolic process; 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 CDD; cd09075; DNase1-like; 1. DR FunFam; 3.60.10.10:FF:000035; Deoxyribonuclease; 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 PDBsum; 1ATN; -. DR PDBsum; 1DNK; -. DR PDBsum; 2A3Z; -. DR PDBsum; 2A40; -. DR PDBsum; 2A41; -. DR PDBsum; 2A42; -. DR PDBsum; 2D1K; -. DR PDBsum; 2DNJ; -. DR PDBsum; 3CJC; -. DR PDBsum; 3DNI; -. DR PDBsum; 3W3D; -. DR PDBsum; 7NXV; -. DR PDBsum; 7NZM; -. DR PDBsum; 9FJU; -. DR PDBsum; 9FJY; -. DR PDBsum; 9NB9; -. PE 1: Evidence at protein level; KW 3D-structure; 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..22 FT /evidence="ECO:0000269|PubMed:4734471" FT CHAIN 23..282 FT /note="Deoxyribonuclease-1" FT /id="PRO_0000007275" FT ACT_SITE 100 FT /evidence="ECO:0000269|PubMed:2395459" FT ACT_SITE 156 FT /evidence="ECO:0000269|PubMed:2395459, FT ECO:0000269|PubMed:4976790" FT SITE 35 FT /note="Involved in actin-binding" FT /evidence="ECO:0000269|PubMed:2395459" FT SITE 87 FT /note="Nitration by tetranitromethane destroys a Ca(2+) FT binding site and inactivates enzyme" FT SITE 89 FT /note="Involved in actin-binding" FT /evidence="ECO:0000269|PubMed:2395459" FT CARBOHYD 40 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:1748997, FT ECO:0000269|PubMed:3560229" FT DISULFID 123..126 FT /evidence="ECO:0000269|PubMed:3713845" FT DISULFID 195..231 FT /note="Essential for enzymatic activity" FT /evidence="ECO:0000269|PubMed:3713845" FT VARIANT 143 FT /note="H -> P (in allele C/D)" FT /evidence="ECO:0000269|PubMed:4735137, FT ECO:0000269|PubMed:4856650" FT CONFLICT 217 FT /note="L -> V (in Ref. 2; AAM93248)" FT /evidence="ECO:0000305" FT STRAND 24..34 FT /evidence="ECO:0007829|PDB:2A40" FT HELIX 35..39 FT /evidence="ECO:0007829|PDB:2A40" FT HELIX 41..51 FT /evidence="ECO:0007829|PDB:2A40" FT STRAND 55..62 FT /evidence="ECO:0007829|PDB:2A40" FT STRAND 65..67 FT /evidence="ECO:0007829|PDB:1ATN" FT HELIX 68..77 FT /evidence="ECO:0007829|PDB:2A40" FT STRAND 79..81 FT /evidence="ECO:0007829|PDB:2A40" FT STRAND 86..89 FT /evidence="ECO:0007829|PDB:2A40" FT HELIX 90..92 FT /evidence="ECO:0007829|PDB:2A40" FT STRAND 95..97 FT /evidence="ECO:0007829|PDB:2A40" FT STRAND 100..106 FT /evidence="ECO:0007829|PDB:2A40" FT TURN 108..110 FT /evidence="ECO:0007829|PDB:2A40" FT STRAND 112..118 FT /evidence="ECO:0007829|PDB:2A40" FT STRAND 121..123 FT /evidence="ECO:0007829|PDB:2A41" FT TURN 124..126 FT /evidence="ECO:0007829|PDB:2A40" FT HELIX 127..130 FT /evidence="ECO:0007829|PDB:2A40" FT STRAND 136..141 FT /evidence="ECO:0007829|PDB:2A40" FT STRAND 145..154 FT /evidence="ECO:0007829|PDB:2A40" FT HELIX 159..161 FT /evidence="ECO:0007829|PDB:2A40" FT HELIX 162..180 FT /evidence="ECO:0007829|PDB:2A40" FT STRAND 185..190 FT /evidence="ECO:0007829|PDB:2A40" FT TURN 195..197 FT /evidence="ECO:0007829|PDB:2A40" FT HELIX 200..205 FT /evidence="ECO:0007829|PDB:2A40" FT HELIX 207..210 FT /evidence="ECO:0007829|PDB:2A40" FT STRAND 214..218 FT /evidence="ECO:0007829|PDB:2A40" FT STRAND 225..228 FT /evidence="ECO:0007829|PDB:2A40" FT STRAND 234..240 FT /evidence="ECO:0007829|PDB:2A40" FT HELIX 241..246 FT /evidence="ECO:0007829|PDB:2A40" FT HELIX 257..260 FT /evidence="ECO:0007829|PDB:2A40" FT HELIX 265..271 FT /evidence="ECO:0007829|PDB:2A40" FT STRAND 277..281 FT /evidence="ECO:0007829|PDB:2A40" SQ SEQUENCE 282 AA; 31346 MW; 43904EF0D5F2E0E2 CRC64; MRGTRLMGLL LALAGLLQLG LSLKIAAFNI RTFGETKMSN ATLASYIVRI VRRYDIVLIQ EVRDSHLVAV GKLLDYLNQD DPNTYHYVVS EPLGRNSYKE RYLFLFRPNK VSVLDTYQYD DGCESCGNDS FSREPAVVKF SSHSTKVKEF AIVALHSAPS DAVAEINSLY DVYLDVQQKW HLNDVMLMGD FNADCSYVTS SQWSSIRLRT SSTFQWLIPD SADTTATSTN CAYDRIVVAG SLLQSSVVPG SAAPFDFQAA YGLSNEMALA ISDHYPVEVT LT //