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 24-JAN-2024, entry version 202. 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. The disease is CC marked by a wide range of system dysfunctions, an elevated erythrocyte CC sedimentation rate, and the formation of LE cells in the blood or bone CC marrow. {ECO:0000269|PubMed:22019780}. Note=The disease is caused by CC variants 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; 9606-ENSP00000378053; -. DR PeptideAtlas; Q13609; -. DR ProteomicsDB; 59596; -. [Q13609-1] DR Antibodypedia; 15158; 230 antibodies from 24 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 AGR; HGNC:2959; -. 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; REPYVVW; -. DR OrthoDB; 5396078at2759; -. DR PhylomeDB; Q13609; -. DR TreeFam; TF329541; -. DR PathwayCommons; Q13609; -. DR SignaLink; Q13609; -. DR BioGRID-ORCS; 1776; 13 hits in 1157 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 161 other cell types or tissues. DR ExpressionAtlas; Q13609; baseline and differential. 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:0004530; F:deoxyribonuclease I activity; IBA:GO_Central. DR GO; GO:0003677; F:DNA binding; IBA:GO_Central. DR GO; GO:0004536; F:DNA nuclease activity; TAS:ProtInc. DR GO; GO:0006309; P:apoptotic DNA fragmentation; IDA:UniProtKB. 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 CDD; cd10282; DNase1; 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:SF32; DEOXYRIBONUCLEASE GAMMA; 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 Genevisible; Q13609; HS. 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 //