DNAS1_HUMAN
ID DNAS1_HUMAN Reviewed; 282 AA.
AC P24855; B4DV35; Q14UU9; Q14UV0;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-1992, sequence version 1.
DT 03-AUG-2022, entry version 213.
DE RecName: Full=Deoxyribonuclease-1;
DE EC=3.1.21.1 {ECO:0000269|PubMed:11241278, ECO:0000269|PubMed:2251263, ECO:0000269|PubMed:2277032};
DE AltName: Full=Deoxyribonuclease I;
DE Short=DNase I;
DE AltName: INN=Dornase alfa;
DE Flags: Precursor;
GN Name=DNASE1 {ECO:0000312|HGNC:HGNC:2956}; Synonyms=DNL1, DRNI;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=2251263; DOI=10.1073/pnas.87.23.9188;
RA Shak S., Capon D.J., Hellmiss R., Marsters S.A., Baker C.L.;
RT "Recombinant human DNase I reduces the viscosity of cystic fibrosis
RT sputum.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:9188-9192(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-244.
RC TISSUE=Placenta;
RX PubMed=7762978; DOI=10.1111/j.1469-1809.1995.tb01601.x;
RA Yasuda T., Kishi K., Yanagawa Y., Yoshida A.;
RT "Structure of the human deoxyribonuclease I (DNase I) gene: identification
RT of the nucleotide substitution that generates its classical genetic
RT polymorphism.";
RL Ann. Hum. Genet. 59:1-15(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, AND
RP COFACTOR.
RX PubMed=11241278;
RX DOI=10.1002/1521-4141(200103)31:3<743::aid-immu743>3.0.co;2-9;
RA Oliveri M., Daga A., Cantoni C., Lunardi C., Millo R., Puccetti A.;
RT "DNase I mediates internucleosomal DNA degradation in human cells
RT undergoing drug-induced apoptosis.";
RL Eur. J. Immunol. 31:743-751(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Pancreas;
RX PubMed=16771825; DOI=10.1111/j.1742-4658.2006.05320.x;
RA Kominato Y., Ueki M., Iida R., Kawai Y., Nakajima T., Makita C., Itoi M.,
RA Tajima Y., Kishi K., Yasuda T.;
RT "Characterization of human deoxyribonuclease I gene (DNASE1) promoters
RT reveals the utilization of two transcription-starting exons and the
RT involvement of Sp1 in its transcriptional regulation.";
RL FEBS J. 273:3094-3105(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Small intestine;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
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 [9]
RP PROTEIN SEQUENCE OF 23-45 AND 73-95.
RC TISSUE=Urine;
RX PubMed=3263467; DOI=10.1084/jem.168.5.1767;
RA Rosenstreich D.L., Tu J.H., Kinkade P.R., Maurer-Fogy I., Kahn J.,
RA Barton R.W., Farina P.R.;
RT "A human urine-derived interleukin 1 inhibitor. Homology with
RT deoxyribonuclease I.";
RL J. Exp. Med. 168:1767-1779(1988).
RN [10]
RP PROTEIN SEQUENCE OF 23-49, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, COFACTOR, AND GLYCOSYLATION AT ASN-40.
RC TISSUE=Urine;
RX PubMed=2277032; DOI=10.1093/oxfordjournals.jbchem.a123212;
RA Yasuda T., Awazu S., Sato W., Iida R., Tanaka Y., Kishi K.;
RT "Human genetically polymorphic deoxyribonuclease: purification,
RT characterization, and multiplicity of urine deoxyribonuclease I.";
RL J. Biochem. 108:393-398(1990).
RN [11]
RP INVOLVEMENT IN SLE.
RX PubMed=11479590; DOI=10.1038/91070;
RA Yasutomo K., Horiuchi T., Kagami S., Tsukamoto H., Hashimura C.,
RA Urushihara M., Kuroda Y.;
RT "Mutation of DNASE1 in people with systemic lupus erythematosus.";
RL Nat. Genet. 28:313-314(2001).
RN [12]
RP INVOLVEMENT IN SLE.
RX PubMed=20439745; DOI=10.1073/pnas.0909927107;
RA Hakkim A., Fuernrohr B.G., Amann K., Laube B., Abed U.A., Brinkmann V.,
RA Herrmann M., Voll R.E., Zychlinsky A.;
RT "Impairment of neutrophil extracellular trap degradation is associated with
RT lupus nephritis.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:9813-9818(2010).
RN [13]
RP VARIANT DNASE1*3.
RX PubMed=7625762; DOI=10.1111/j.1469-1809.1995.tb00737.x;
RA Yasuda T., Nadano D., Takeshita H., Tenjo E., Kishi K.;
RT "Molecular analysis of the third allele of human deoxyribonuclease I
RT polymorphism.";
RL Ann. Hum. Genet. 59:139-147(1995).
RN [14]
RP VARIANT DNASE1*4.
RX PubMed=7867802; DOI=10.1016/0014-5793(95)00037-a;
RA Yasuda T., Nadano D., Takeshita H., Tenjo E., Sawazaki K., Ootani M.,
RA Kishi K.;
RT "The molecular basis for genetic polymorphism of human deoxyribonuclease I:
RT identification of the nucleotide substitution that generates the fourth
RT allele.";
RL FEBS Lett. 359:211-214(1995).
RN [15]
RP VARIANT DNASE1*5.
RX PubMed=9420147; DOI=10.1002/elps.1150181108;
RA Iida R., Yasuda T., Aoyama M., Tsubota E., Kobayashi M., Yuasa I.,
RA Matsuki T., Kishi K.;
RT "The fifth allele of the human deoxyribonuclease I (DNase I)
RT polymorphism.";
RL Electrophoresis 18:1936-1939(1997).
RN [16]
RP VARIANT DNASE1*6.
RX PubMed=10381379; DOI=10.1006/bbrc.1999.0900;
RA Yasuda T., Takeshita H., Iida R., Kogure S., Kishi K.;
RT "A new allele, DNASE1*6, of human deoxyribonuclease I polymorphism encodes
RT an Arg to Cys substitution responsible for its instability.";
RL Biochem. Biophys. Res. Commun. 260:280-283(1999).
CC -!- FUNCTION: Serum endocuclease secreted into body fluids by a wide
CC variety of exocrine and endocrine organs (PubMed:2251263,
CC PubMed:11241278, PubMed:2277032). Expressed by non-hematopoietic
CC tissues and preferentially cleaves protein-free DNA (By similarity).
CC Among other functions, seems to be involved in cell death by apoptosis
CC (PubMed:11241278). 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) (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:P00639, ECO:0000250|UniProtKB:P21704,
CC ECO:0000250|UniProtKB:P49183, ECO:0000269|PubMed:11241278,
CC ECO:0000269|PubMed:2251263, ECO:0000269|PubMed:2277032}.
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:11241278, ECO:0000269|PubMed:2251263,
CC ECO:0000269|PubMed:2277032};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:11241278, ECO:0000269|PubMed:2277032};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11241278, ECO:0000269|PubMed:2277032};
CC Note=Divalent metal cations. Prefers Ca(2+) or Mg(2+).
CC {ECO:0000269|PubMed:11241278, ECO:0000269|PubMed:2277032};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2277032}. Zymogen
CC granule {ECO:0000305}. Nucleus envelope. Note=Secretory protein, stored
CC in zymogen granules and found in the nuclear envelope.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P24855-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P24855-2; Sequence=VSP_056974, VSP_056975, VSP_056976;
CC -!- TISSUE SPECIFICITY: Principally in tissues of the digestive system.
CC Highest levels found in urine, but also relatively abundant in semen
CC and saliva.
CC -!- POLYMORPHISM: At least 6 alleles of DNASE1 are known: DNASE1*1 to
CC DNASE1*6. The sequence shown is that of DNASE1*2.
CC {ECO:0000269|PubMed:10381379, ECO:0000269|PubMed:7625762,
CC ECO:0000269|PubMed:7867802, ECO:0000269|PubMed:9420147}.
CC -!- DISEASE: Systemic lupus erythematosus (SLE) [MIM:152700]: A chronic,
CC relapsing, inflammatory, and often febrile multisystemic disorder of
CC connective tissue, characterized principally by involvement of the
CC skin, joints, kidneys and serosal membranes. It is of unknown etiology,
CC but is thought to represent a failure of the regulatory mechanisms of
CC the autoimmune system. The disease is marked by a wide range of system
CC dysfunctions, an elevated erythrocyte sedimentation rate, and the
CC formation of LE cells in the blood or bone marrow.
CC {ECO:0000269|PubMed:11479590, ECO:0000269|PubMed:20439745}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry. Neutrophil extracellular traps (NETs)
CC are impaired in patients suffering from SLE (PubMed:20439745). NETs are
CC mainly composed of DNA fibers and are released by neutrophils to bind
CC pathogens during inflammation (PubMed:20439745).
CC {ECO:0000269|PubMed:20439745}.
CC -!- PHARMACEUTICAL: Available under the name Pulmozyme (Genentech). Used to
CC reduce the viscosity of cystic fibrosis sputum by hydrolyzing the
CC extracellular DNA released by degenerating leukocytes that accumulate
CC in response to infection. {ECO:0000305|PubMed:2251263}.
CC -!- SIMILARITY: Belongs to the DNase I family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Pulmozyme; Note=Clinical information on Pulmozyme;
CC URL="https://www.pulmozyme.com/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Deoxyribonuclease entry;
CC URL="https://en.wikipedia.org/wiki/Deoxyribonuclease";
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; M55983; AAA63170.1; -; mRNA.
DR EMBL; D83195; BAA11841.1; -; Genomic_DNA.
DR EMBL; AJ298844; CAC12813.1; -; mRNA.
DR EMBL; AB188151; BAE96964.1; -; mRNA.
DR EMBL; AB188152; BAE96965.1; -; mRNA.
DR EMBL; AK300914; BAG62547.1; -; mRNA.
DR EMBL; AC005203; AAC24721.1; -; Genomic_DNA.
DR EMBL; AC006111; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471112; EAW85344.1; -; Genomic_DNA.
DR EMBL; BC029437; AAH29437.1; -; mRNA.
DR CCDS; CCDS10507.1; -. [P24855-1]
DR PIR; A38417; NDHU1.
DR RefSeq; NP_005214.2; NM_005223.3. [P24855-1]
DR RefSeq; XP_011520695.1; XM_011522393.2. [P24855-1]
DR RefSeq; XP_016878488.1; XM_017022999.1.
DR RefSeq; XP_016878492.1; XM_017023003.1. [P24855-2]
DR RefSeq; XP_016878493.1; XM_017023004.1. [P24855-2]
DR RefSeq; XP_016878494.1; XM_017023005.1. [P24855-2]
DR RefSeq; XP_016878495.1; XM_017023006.1. [P24855-2]
DR PDB; 4AWN; X-ray; 1.95 A; A=23-282.
DR PDBsum; 4AWN; -.
DR AlphaFoldDB; P24855; -.
DR SMR; P24855; -.
DR BioGRID; 108112; 2.
DR STRING; 9606.ENSP00000385905; -.
DR BindingDB; P24855; -.
DR ChEMBL; CHEMBL3351219; -.
DR GlyConnect; 2005; 1 N-Linked glycan (1 site).
DR GlyGen; P24855; 2 sites, 1 N-linked glycan (1 site).
DR iPTMnet; P24855; -.
DR PhosphoSitePlus; P24855; -.
DR BioMuta; DNASE1; -.
DR DMDM; 118919; -.
DR jPOST; P24855; -.
DR MassIVE; P24855; -.
DR PaxDb; P24855; -.
DR PeptideAtlas; P24855; -.
DR PRIDE; P24855; -.
DR ProteomicsDB; 5238; -.
DR ProteomicsDB; 54233; -. [P24855-1]
DR Antibodypedia; 10879; 279 antibodies from 32 providers.
DR DNASU; 1773; -.
DR Ensembl; ENST00000246949.10; ENSP00000246949.5; ENSG00000213918.11. [P24855-1]
DR Ensembl; ENST00000407479.5; ENSP00000385905.1; ENSG00000213918.11. [P24855-1]
DR GeneID; 1773; -.
DR KEGG; hsa:1773; -.
DR MANE-Select; ENST00000246949.10; ENSP00000246949.5; NM_005223.4; NP_005214.2.
DR UCSC; uc002cvr.4; human. [P24855-1]
DR CTD; 1773; -.
DR DisGeNET; 1773; -.
DR GeneCards; DNASE1; -.
DR HGNC; HGNC:2956; DNASE1.
DR HPA; ENSG00000213918; Tissue enhanced (intestine).
DR MalaCards; DNASE1; -.
DR MIM; 125505; gene.
DR MIM; 152700; phenotype.
DR neXtProt; NX_P24855; -.
DR OpenTargets; ENSG00000213918; -.
DR Orphanet; 300345; Autosomal systemic lupus erythematosus.
DR Orphanet; 536; Systemic lupus erythematosus.
DR PharmGKB; PA27427; -.
DR VEuPathDB; HostDB:ENSG00000213918; -.
DR eggNOG; ENOG502QQFT; Eukaryota.
DR GeneTree; ENSGT00950000182846; -.
DR HOGENOM; CLU_043335_2_1_1; -.
DR InParanoid; P24855; -.
DR OMA; SCPFTEV; -.
DR OrthoDB; 1282784at2759; -.
DR PhylomeDB; P24855; -.
DR TreeFam; TF329541; -.
DR BRENDA; 3.1.21.1; 2681.
DR PathwayCommons; P24855; -.
DR SignaLink; P24855; -.
DR SIGNOR; P24855; -.
DR BioGRID-ORCS; 1773; 10 hits in 1083 CRISPR screens.
DR ChiTaRS; DNASE1; human.
DR GeneWiki; Deoxyribonuclease_I; -.
DR GenomeRNAi; 1773; -.
DR Pharos; P24855; Tchem.
DR PRO; PR:P24855; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P24855; protein.
DR Bgee; ENSG00000213918; Expressed in duodenum and 147 other tissues.
DR ExpressionAtlas; P24855; baseline and differential.
DR Genevisible; P24855; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:ProtInc.
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; Alternative splicing; Apoptosis; Calcium;
KW Cytoplasmic vesicle; Direct protein sequencing; Disulfide bond;
KW Endonuclease; Glycoprotein; Hydrolase; Nuclease; Nucleus; Pharmaceutical;
KW Reference proteome; Secreted; Signal; Systemic lupus erythematosus.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:2277032,
FT ECO:0000269|PubMed:3263467"
FT CHAIN 23..282
FT /note="Deoxyribonuclease-1"
FT /id="PRO_0000007277"
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:0000269|PubMed:2277032"
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 VAR_SEQ 1..66
FT /note="MRGMKLLGALLALAALLQGAVSLKIAAFNIQTFGETKMSNATLVSYIVQILS
FT RYDIALVQEVRDSH -> MHQTPITTWSVSHWDGTAIRSATCSCTGLTRCLRWTATTTM
FT MAASPAGTTPSTESQPLSGSSPGSQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056974"
FT VAR_SEQ 67..183
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056975"
FT VAR_SEQ 268..282
FT /note="AQAISDHYPVEVMLK -> FSVHTCSGAGLGERHGLPASAALPSNTCRAGTH
FT RVST (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056976"
FT VARIANT 2
FT /note="R -> S (in dbSNP:rs8176927)"
FT /id="VAR_024434"
FT VARIANT 31
FT /note="Q -> E (in allele DNASE1*4; dbSNP:rs77254040)"
FT /id="VAR_002264"
FT VARIANT 107
FT /note="R -> G (in dbSNP:rs8176928)"
FT /id="VAR_029172"
FT VARIANT 114
FT /note="V -> M (in allele DNASE1*5; dbSNP:rs530214101)"
FT /id="VAR_009300"
FT VARIANT 127
FT /note="G -> R (in dbSNP:rs8176919)"
FT /id="VAR_024435"
FT VARIANT 154
FT /note="P -> A (in allele DNASE1*3; dbSNP:rs1799891)"
FT /id="VAR_002265"
FT VARIANT 207
FT /note="R -> C (in allele DNASE1*6; dbSNP:rs148373909)"
FT /id="VAR_009301"
FT VARIANT 231
FT /note="C -> Y (in dbSNP:rs8176940)"
FT /id="VAR_029173"
FT VARIANT 244
FT /note="R -> Q (in allele DNASE1*1; dbSNP:rs1053874)"
FT /evidence="ECO:0000269|PubMed:7762978"
FT /id="VAR_002266"
FT VARIANT 246
FT /note="A -> P (in dbSNP:rs8176939)"
FT /id="VAR_029174"
FT VARIANT 262
FT /note="G -> D (in dbSNP:rs8176924)"
FT /id="VAR_029175"
FT CONFLICT 143
FT /note="R -> Q (in Ref. 4; BAE96964)"
FT /evidence="ECO:0000305"
FT STRAND 24..34
FT /evidence="ECO:0007829|PDB:4AWN"
FT HELIX 35..38
FT /evidence="ECO:0007829|PDB:4AWN"
FT HELIX 41..51
FT /evidence="ECO:0007829|PDB:4AWN"
FT STRAND 55..62
FT /evidence="ECO:0007829|PDB:4AWN"
FT HELIX 68..77
FT /evidence="ECO:0007829|PDB:4AWN"
FT TURN 78..80
FT /evidence="ECO:0007829|PDB:4AWN"
FT STRAND 86..89
FT /evidence="ECO:0007829|PDB:4AWN"
FT STRAND 93..98
FT /evidence="ECO:0007829|PDB:4AWN"
FT STRAND 100..106
FT /evidence="ECO:0007829|PDB:4AWN"
FT TURN 108..110
FT /evidence="ECO:0007829|PDB:4AWN"
FT STRAND 112..118
FT /evidence="ECO:0007829|PDB:4AWN"
FT TURN 124..127
FT /evidence="ECO:0007829|PDB:4AWN"
FT STRAND 136..141
FT /evidence="ECO:0007829|PDB:4AWN"
FT STRAND 149..154
FT /evidence="ECO:0007829|PDB:4AWN"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:4AWN"
FT HELIX 162..180
FT /evidence="ECO:0007829|PDB:4AWN"
FT STRAND 185..190
FT /evidence="ECO:0007829|PDB:4AWN"
FT TURN 195..197
FT /evidence="ECO:0007829|PDB:4AWN"
FT HELIX 200..205
FT /evidence="ECO:0007829|PDB:4AWN"
FT HELIX 207..210
FT /evidence="ECO:0007829|PDB:4AWN"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:4AWN"
FT STRAND 225..228
FT /evidence="ECO:0007829|PDB:4AWN"
FT STRAND 234..240
FT /evidence="ECO:0007829|PDB:4AWN"
FT HELIX 241..246
FT /evidence="ECO:0007829|PDB:4AWN"
FT HELIX 257..260
FT /evidence="ECO:0007829|PDB:4AWN"
FT HELIX 265..271
FT /evidence="ECO:0007829|PDB:4AWN"
FT STRAND 277..281
FT /evidence="ECO:0007829|PDB:4AWN"
SQ SEQUENCE 282 AA; 31434 MW; 040042E2D23555B6 CRC64;
MRGMKLLGAL LALAALLQGA VSLKIAAFNI QTFGETKMSN ATLVSYIVQI LSRYDIALVQ
EVRDSHLTAV GKLLDNLNQD APDTYHYVVS EPLGRNSYKE RYLFVYRPDQ VSAVDSYYYD
DGCEPCGNDT FNREPAIVRF FSRFTEVREF AIVPLHAAPG DAVAEIDALY DVYLDVQEKW
GLEDVMLMGD FNAGCSYVRP SQWSSIRLWT SPTFQWLIPD SADTTATPTH CAYDRIVVAG
MLLRGAVVPD SALPFNFQAA YGLSDQLAQA ISDHYPVEVM LK
