DNAS1_BOVIN
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 03-AUG-2022, entry version 188.
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:4976790,
CC PubMed:5166750, PubMed:3352748, PubMed:2395459). 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 -!- WEB RESOURCE: Name=Worthington enzyme manual;
CC URL="https://www.worthington-biochem.com/DNASE/";
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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_010817356.1; XM_010819054.2.
DR RefSeq; XP_015315660.1; XM_015460174.1.
DR RefSeq; XP_015315661.1; XM_015460175.1.
DR RefSeq; XP_015315662.1; XM_015460176.1.
DR RefSeq; XP_015315663.1; XM_015460177.1.
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 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 AlphaFoldDB; P00639; -.
DR PCDDB; P00639; -.
DR SMR; P00639; -.
DR DIP; DIP-541N; -.
DR IntAct; P00639; 2.
DR MINT; P00639; -.
DR STRING; 9913.ENSBTAP00000054758; -.
DR BindingDB; P00639; -.
DR ChEMBL; CHEMBL5712; -.
DR iPTMnet; P00639; -.
DR PaxDb; P00639; -.
DR Ensembl; ENSBTAT00000026784; ENSBTAP00000026784; ENSBTAG00000020107.
DR GeneID; 282217; -.
DR KEGG; bta:282217; -.
DR CTD; 1773; -.
DR VEuPathDB; HostDB:ENSBTAG00000020107; -.
DR VGNC; VGNC:28132; DNASE1.
DR eggNOG; ENOG502QQFT; Eukaryota.
DR GeneTree; ENSGT00950000182846; -.
DR HOGENOM; CLU_043335_2_1_1; -.
DR InParanoid; P00639; -.
DR OMA; YLYVFRP; -.
DR OrthoDB; 1282784at2759; -.
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 tissues.
DR ExpressionAtlas; P00639; 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; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006308; P:DNA catabolic process; IBA:GO_Central.
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; IPR033125; DNASE_I_2.
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.
DR PROSITE; PS00918; DNASE_I_2; 1.
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 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
