DNSL3_HUMAN
ID DNSL3_HUMAN Reviewed; 305 AA.
AC Q13609; B2R8B1; B7Z707; O75803;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Deoxyribonuclease gamma;
DE Short=DNase gamma;
DE EC=3.1.21.-;
DE AltName: Full=DNase I homolog protein DHP2;
DE AltName: Full=Deoxyribonuclease I-like 3;
DE Short=DNase I-like 3;
DE AltName: Full=Liver and spleen DNase;
DE Short=LS-DNase;
DE Short=LSD;
DE Flags: Precursor;
GN Name=DNASE1L3 {ECO:0000312|HGNC:HGNC:2959}; Synonyms=DHP2, DNAS1L3;
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).
RX PubMed=9205125; DOI=10.1006/geno.1997.4748;
RA Rodriguez A.M., Rodin D., Nomura H., Morton C.C., Weremowicz S.,
RA Schneider M.C.;
RT "Identification, localization, and expression of two novel human genes
RT similar to deoxyribonuclease I.";
RL Genomics 42:507-513(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RX PubMed=9070308; DOI=10.1006/bbrc.1996.5923;
RA Zeng Z., Parmelee D., Hyaw H., Coleman T.A., Su K., Zhang J., Gentz R.,
RA Ruben S., Rosen C., Li Y.;
RT "Cloning and characterization of a novel human DNase.";
RL Biochem. Biophys. Res. Commun. 231:499-504(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=9714828; DOI=10.1016/s0378-1119(98)00281-9;
RA Baron W.F., Pan C.Q., Spencer S.A., Ryan A.M., Lazarus R.A., Baker K.P.;
RT "Cloning and characterization of an actin-resistant DNase I-like
RT endonuclease secreted by macrophages.";
RL Gene 215:291-301(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND VARIANT LYS-96.
RC TISSUE=Spleen;
RX PubMed=14646506; DOI=10.1023/a:1009692807692;
RA Shiokawa D., Hirai M., Tanuma S.;
RT "cDNA cloning of human DNase gamma: chromosomal localization of its gene
RT and enzymatic properties of recombinant protein.";
RL Apoptosis 3:89-95(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Spleen;
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=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Liver;
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 FUNCTION, COFACTOR, AND ADP-RIBOSYLATION.
RX PubMed=10807908; DOI=10.1074/jbc.m001087200;
RA Yakovlev A.G., Wang G., Stoica B.A., Boulares H.A., Spoonde A.Y.,
RA Yoshihara K., Smulson M.E.;
RT "A role of the Ca2+/Mg2+-dependent endonuclease in apoptosis and its
RT inhibition by poly(ADP-ribose) polymerase.";
RL J. Biol. Chem. 275:21302-21308(2000).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11141064; DOI=10.1021/bi001041a;
RA Shiokawa D., Tanuma S.;
RT "Characterization of human DNase I family endonucleases and activation of
RT DNase gamma during apoptosis.";
RL Biochemistry 40:143-152(2001).
RN [11]
RP INVOLVEMENT IN SLEB16, AND VARIANT CYS-206.
RX PubMed=22019780; DOI=10.1038/ng.975;
RA Al-Mayouf S.M., Sunker A., Abdwani R., Abrawi S.A., Almurshedi F.,
RA Alhashmi N., Al Sonbul A., Sewairi W., Qari A., Abdallah E., Al-Owain M.,
RA Al Motywee S., Al-Rayes H., Hashem M., Khalak H., Al-Jebali L.,
RA Alkuraya F.S.;
RT "Loss-of-function variant in DNASE1L3 causes a familial form of systemic
RT lupus erythematosus.";
RL Nat. Genet. 43:1186-1188(2011).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23229555; DOI=10.1074/jbc.m112.423061;
RA Errami Y., Naura A.S., Kim H., Ju J., Suzuki Y., El-Bahrawy A.H.,
RA Ghonim M.A., Hemeida R.A., Mansy M.S., Zhang J., Xu M., Smulson M.E.,
RA Brim H., Boulares A.H.;
RT "Apoptotic DNA fragmentation may be a cooperative activity between caspase-
RT activated deoxyribonuclease and the poly(ADP-ribose) polymerase-regulated
RT DNAS1L3, an endoplasmic reticulum-localized endonuclease that translocates
RT to the nucleus during apoptosis.";
RL J. Biol. Chem. 288:3460-3468(2013).
RN [13]
RP FUNCTION.
RX PubMed=24312463; DOI=10.1371/journal.pone.0080223;
RA Mizuta R., Araki S., Furukawa M., Furukawa Y., Ebara S., Shiokawa D.,
RA Hayashi K., Tanuma S., Kitamura D.;
RT "DNase gamma is the effector endonuclease for internucleosomal DNA
RT fragmentation in necrosis.";
RL PLoS ONE 8:E80223-E80223(2013).
RN [14]
RP FUNCTION, AND CHARACTERIZATION OF VARIANT CYS-206.
RX PubMed=27293190; DOI=10.1016/j.cell.2016.05.034;
RA Sisirak V., Sally B., D'Agati V., Martinez-Ortiz W., Oezcakar Z.B.,
RA David J., Rashidfarrokhi A., Yeste A., Panea C., Chida A.S., Bogunovic M.,
RA Ivanov I.I., Quintana F.J., Sanz I., Elkon K.B., Tekin M., Yalcinkaya F.,
RA Cardozo T.J., Clancy R.M., Buyon J.P., Reizis B.;
RT "Digestion of chromatin in apoptotic cell microparticles prevents
RT autoimmunity.";
RL Cell 166:88-101(2016).
RN [15]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-19; ARG-82 AND SER-117.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [16]
RP VARIANT CYS-206, AND CHARACTERIZATION OF VARIANT CYS-206.
RX PubMed=19559017; DOI=10.1016/j.cca.2009.06.022;
RA Ueki M., Takeshita H., Fujihara J., Iida R., Yuasa I., Kato H., Panduro A.,
RA Nakajima T., Kominato Y., Yasuda T.;
RT "Caucasian-specific allele in non-synonymous single nucleotide
RT polymorphisms of the gene encoding deoxyribonuclease I-like 3, potentially
RT relevant to autoimmunity, produces an inactive enzyme.";
RL Clin. Chim. Acta 407:20-24(2009).
RN [17]
RP VARIANTS ARG-82 AND MET-243, AND CHARACTERIZATION OF VARIANT ARG-82.
RX PubMed=21692081; DOI=10.1002/elps.201100064;
RA Ueki M., Fujihara J., Takeshita H., Kimura-Kataoka K., Iida R., Yuasa I.,
RA Kato H., Yasuda T.;
RT "Global genetic analysis of all single nucleotide polymorphisms in exons of
RT the human deoxyribonuclease I-like 3 gene and their effect on its catalytic
RT activity.";
RL Electrophoresis 32:1465-1472(2011).
CC -!- FUNCTION: Has DNA hydrolytic activity. Is capable of both single- and
CC double-stranded DNA cleavage, producing DNA fragments with 3'-OH ends
CC (By similarity). Can cleave chromatin to nucleosomal units and cleaves
CC nucleosomal and liposome-coated DNA (PubMed:9070308, PubMed:9714828,
CC PubMed:14646506, PubMed:10807908, PubMed:27293190). Acts in
CC internucleosomal DNA fragmentation (INDF) during apoptosis and necrosis
CC (PubMed:23229555, PubMed:24312463). The role in apoptosis includes
CC myogenic and neuronal differentiation, and BCR-mediated clonal deletion
CC of self-reactive B cells (By similarity). Is active on chromatin in
CC apoptotic cell-derived membrane-coated microparticles and thus
CC suppresses anti-DNA autoimmunity (PubMed:27293190). Together with
CC DNASE1, plays a key role in degrading neutrophil extracellular traps
CC (NETs) (By similarity). NETs are mainly composed of DNA fibers and are
CC released by neutrophils to bind pathogens during inflammation (By
CC similarity). Degradation of intravascular NETs by DNASE1 and DNASE1L3
CC is required to prevent formation of clots that obstruct blood vessels
CC and cause organ damage following inflammation (By similarity).
CC {ECO:0000250|UniProtKB:O55070, ECO:0000250|UniProtKB:O89107,
CC ECO:0000269|PubMed:10807908, ECO:0000269|PubMed:14646506,
CC ECO:0000269|PubMed:23229555, ECO:0000269|PubMed:24312463,
CC ECO:0000269|PubMed:27293190, ECO:0000269|PubMed:9070308,
CC ECO:0000269|PubMed:9714828}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:10807908};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10807908};
CC -!- ACTIVITY REGULATION: Inhibited by zinc. {ECO:0000250|UniProtKB:O89107}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is about 7.2.;
CC -!- INTERACTION:
CC Q13609; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-9512718, EBI-3867333;
CC Q13609; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-9512718, EBI-3958099;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11141064,
CC ECO:0000269|PubMed:23229555}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:23229555}. Secreted {ECO:0000269|PubMed:9714828}.
CC Note=Translocates from the endoplasmic reticulum to the nucleus during
CC apoptosis (PubMed:23229555). Contradictory reports exist about the
CC subcellular localization under normal physiological conditions. Under
CC conditions of cell death, may diffuse and/or be actively transported to
CC the nucleus. {ECO:0000269|PubMed:23229555, ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13609-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13609-2; Sequence=VSP_047251;
CC -!- TISSUE SPECIFICITY: Liver and spleen.
CC -!- PTM: Poly-ADP-ribosylated by PARP1. ADP-ribosylation negatively
CC regulates enzymatic activity during apoptosis.
CC {ECO:0000305|PubMed:10807908}.
CC -!- DISEASE: Systemic lupus erythematosus 16 (SLEB16) [MIM:614420]: A rare
CC autosomal recessive form of systemic lupus erythematosus with childhood
CC onset, characterized by high frequency of anti-neutrophil cytoplasmic
CC antibodies and lupus nephritis. Systemic lupus erythematosus is a
CC chronic, relapsing, inflammatory, and often febrile multisystemic
CC disorder of connective tissue, characterized principally by involvement
CC of the skin, joints, kidneys and serosal membranes. It is of unknown
CC etiology, but is thought to represent a failure of the regulatory
CC mechanisms of the autoimmune system. The disease is marked by a wide
CC range of system dysfunctions, an elevated erythrocyte sedimentation
CC rate, and the formation of LE cells in the blood or bone marrow.
CC {ECO:0000269|PubMed:22019780}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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; U56814; AAB63967.1; -; mRNA.
DR EMBL; AF047354; AAC35752.1; -; mRNA.
DR EMBL; U75744; AAC23652.1; -; mRNA.
DR EMBL; AK301263; BAH13443.1; -; mRNA.
DR EMBL; AK313303; BAG36108.1; -; mRNA.
DR EMBL; AC137936; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW65358.1; -; Genomic_DNA.
DR EMBL; BC015831; AAH15831.1; -; mRNA.
DR CCDS; CCDS2886.1; -. [Q13609-1]
DR CCDS; CCDS58836.1; -. [Q13609-2]
DR PIR; JC5361; JC5361.
DR RefSeq; NP_001243489.1; NM_001256560.1. [Q13609-2]
DR RefSeq; NP_004935.1; NM_004944.3. [Q13609-1]
DR PDB; 7KIU; X-ray; 2.22 A; A/B/C/D=21-282.
DR PDBsum; 7KIU; -.
DR AlphaFoldDB; Q13609; -.
DR SMR; Q13609; -.
DR BioGRID; 108115; 3.
DR IntAct; Q13609; 5.
DR MINT; Q13609; -.
DR STRING; 9606.ENSP00000378053; -.
DR BindingDB; Q13609; -.
DR ChEMBL; CHEMBL1649048; -.
DR iPTMnet; Q13609; -.
DR PhosphoSitePlus; Q13609; -.
DR BioMuta; DNASE1L3; -.
DR DMDM; 2494173; -.
DR MassIVE; Q13609; -.
DR PaxDb; Q13609; -.
DR PeptideAtlas; Q13609; -.
DR PRIDE; Q13609; -.
DR ProteomicsDB; 59596; -. [Q13609-1]
DR Antibodypedia; 15158; 203 antibodies from 23 providers.
DR DNASU; 1776; -.
DR Ensembl; ENST00000394549.7; ENSP00000378053.2; ENSG00000163687.14. [Q13609-1]
DR Ensembl; ENST00000486455.5; ENSP00000419052.1; ENSG00000163687.14. [Q13609-2]
DR GeneID; 1776; -.
DR KEGG; hsa:1776; -.
DR MANE-Select; ENST00000394549.7; ENSP00000378053.2; NM_004944.4; NP_004935.1.
DR UCSC; uc003djo.3; human. [Q13609-1]
DR CTD; 1776; -.
DR DisGeNET; 1776; -.
DR GeneCards; DNASE1L3; -.
DR HGNC; HGNC:2959; DNASE1L3.
DR HPA; ENSG00000163687; Group enriched (liver, lymphoid tissue).
DR MalaCards; DNASE1L3; -.
DR MIM; 602244; gene.
DR MIM; 614420; phenotype.
DR neXtProt; NX_Q13609; -.
DR OpenTargets; ENSG00000163687; -.
DR Orphanet; 300345; Autosomal systemic lupus erythematosus.
DR Orphanet; 36412; Hypocomplementemic urticarial vasculitis.
DR PharmGKB; PA27430; -.
DR VEuPathDB; HostDB:ENSG00000163687; -.
DR eggNOG; ENOG502QPNY; Eukaryota.
DR GeneTree; ENSGT00950000182846; -.
DR HOGENOM; CLU_043335_0_1_1; -.
DR InParanoid; Q13609; -.
DR OMA; SRCDIML; -.
DR PhylomeDB; Q13609; -.
DR TreeFam; TF329541; -.
DR PathwayCommons; Q13609; -.
DR SignaLink; Q13609; -.
DR BioGRID-ORCS; 1776; 12 hits in 1078 CRISPR screens.
DR ChiTaRS; DNASE1L3; human.
DR GeneWiki; DNASE1L3; -.
DR GenomeRNAi; 1776; -.
DR Pharos; Q13609; Tbio.
DR PRO; PR:Q13609; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q13609; protein.
DR Bgee; ENSG00000163687; Expressed in periodontal ligament and 160 other tissues.
DR ExpressionAtlas; Q13609; baseline and differential.
DR Genevisible; Q13609; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; TAS:ProtInc.
DR GO; GO:0004536; F:deoxyribonuclease activity; TAS:ProtInc.
DR GO; GO:0004530; F:deoxyribonuclease I activity; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR GO; GO:0006309; P:apoptotic DNA fragmentation; IDA:UniProtKB.
DR GO; GO:0006308; P:DNA catabolic process; IBA:GO_Central.
DR GO; GO:0000737; P:DNA catabolic process, endonucleolytic; IBA:GO_Central.
DR GO; GO:0006259; P:DNA metabolic process; TAS:ProtInc.
DR GO; GO:0002283; P:neutrophil activation involved in immune response; ISS:UniProtKB.
DR GO; GO:0010623; P:programmed cell death involved in cell development; IBA:GO_Central.
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; ADP-ribosylation; Alternative splicing; Apoptosis; Calcium;
KW Disulfide bond; Endonuclease; Endoplasmic reticulum; Hydrolase; Necrosis;
KW Nuclease; Nucleus; Reference proteome; Secreted; Signal;
KW Systemic lupus erythematosus.
FT SIGNAL 1..20
FT /evidence="ECO:0000250"
FT CHAIN 21..305
FT /note="Deoxyribonuclease gamma"
FT /id="PRO_0000007288"
FT REGION 284..305
FT /note="Not required for free DNA-nuclease activity but
FT required for activity towards liposome-coated DNA"
FT /evidence="ECO:0000250|UniProtKB:O55070"
FT MOTIF 35..51
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 296..304
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 100
FT /evidence="ECO:0000250|UniProtKB:P00639"
FT ACT_SITE 155
FT /evidence="ECO:0000250|UniProtKB:P00639"
FT DISULFID 194..231
FT /note="Essential for enzymatic activity"
FT /evidence="ECO:0000250|UniProtKB:O55070"
FT VAR_SEQ 78..107
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_047251"
FT VARIANT 19
FT /note="L -> V (in a breast cancer sample; somatic mutation;
FT dbSNP:rs763778721)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036079"
FT VARIANT 82
FT /note="G -> R (in a breast cancer sample; somatic mutation;
FT diminishes enzymatic activity; dbSNP:rs74350392)"
FT /evidence="ECO:0000269|PubMed:16959974,
FT ECO:0000269|PubMed:21692081"
FT /id="VAR_036080"
FT VARIANT 96
FT /note="N -> K (in dbSNP:rs12491947)"
FT /evidence="ECO:0000269|PubMed:14646506"
FT /id="VAR_059249"
FT VARIANT 117
FT /note="Y -> S (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036081"
FT VARIANT 206
FT /note="R -> C (abolishes enzymatic activity;
FT dbSNP:rs35677470)"
FT /evidence="ECO:0000269|PubMed:19559017,
FT ECO:0000269|PubMed:22019780, ECO:0000269|PubMed:27293190"
FT /id="VAR_076797"
FT VARIANT 243
FT /note="I -> M (in dbSNP:rs76440799)"
FT /evidence="ECO:0000269|PubMed:19559017"
FT /id="VAR_061137"
FT STRAND 21..32
FT /evidence="ECO:0007829|PDB:7KIU"
FT HELIX 33..37
FT /evidence="ECO:0007829|PDB:7KIU"
FT HELIX 39..50
FT /evidence="ECO:0007829|PDB:7KIU"
FT STRAND 53..60
FT /evidence="ECO:0007829|PDB:7KIU"
FT HELIX 67..75
FT /evidence="ECO:0007829|PDB:7KIU"
FT HELIX 79..82
FT /evidence="ECO:0007829|PDB:7KIU"
FT STRAND 85..89
FT /evidence="ECO:0007829|PDB:7KIU"
FT STRAND 93..97
FT /evidence="ECO:0007829|PDB:7KIU"
FT STRAND 100..107
FT /evidence="ECO:0007829|PDB:7KIU"
FT TURN 108..110
FT /evidence="ECO:0007829|PDB:7KIU"
FT STRAND 112..118
FT /evidence="ECO:0007829|PDB:7KIU"
FT STRAND 126..129
FT /evidence="ECO:0007829|PDB:7KIU"
FT STRAND 135..140
FT /evidence="ECO:0007829|PDB:7KIU"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:7KIU"
FT STRAND 148..155
FT /evidence="ECO:0007829|PDB:7KIU"
FT HELIX 158..160
FT /evidence="ECO:0007829|PDB:7KIU"
FT HELIX 161..178
FT /evidence="ECO:0007829|PDB:7KIU"
FT STRAND 184..189
FT /evidence="ECO:0007829|PDB:7KIU"
FT TURN 194..196
FT /evidence="ECO:0007829|PDB:7KIU"
FT HELIX 199..204
FT /evidence="ECO:0007829|PDB:7KIU"
FT HELIX 206..209
FT /evidence="ECO:0007829|PDB:7KIU"
FT STRAND 213..217
FT /evidence="ECO:0007829|PDB:7KIU"
FT STRAND 224..226
FT /evidence="ECO:0007829|PDB:7KIU"
FT STRAND 234..239
FT /evidence="ECO:0007829|PDB:7KIU"
FT HELIX 241..244
FT /evidence="ECO:0007829|PDB:7KIU"
FT HELIX 257..260
FT /evidence="ECO:0007829|PDB:7KIU"
FT HELIX 265..271
FT /evidence="ECO:0007829|PDB:7KIU"
FT STRAND 277..281
FT /evidence="ECO:0007829|PDB:7KIU"
SQ SEQUENCE 305 AA; 35504 MW; BAB9F1A0341E6048 CRC64;
MSRELAPLLL LLLSIHSALA MRICSFNVRS FGESKQEDKN AMDVIVKVIK RCDIILVMEI
KDSNNRICPI LMEKLNRNSR RGITYNYVIS SRLGRNTYKE QYAFLYKEKL VSVKRSYHYH
DYQDGDADVF SREPFVVWFQ SPHTAVKDFV IIPLHTTPET SVKEIDELVE VYTDVKHRWK
AENFIFMGDF NAGCSYVPKK AWKNIRLRTD PRFVWLIGDQ EDTTVKKSTN CAYDRIVLRG
QEIVSSVVPK SNSVFDFQKA YKLTEEEALD VSDHFPVEFK LQSSRAFTNS KKSVTLRKKT
KSKRS
