DNSL3_RAT
ID DNSL3_RAT Reviewed; 310 AA.
AC O89107;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Deoxyribonuclease gamma;
DE Short=DNase gamma;
DE EC=3.1.21.-;
DE AltName: Full=DNaseY;
DE AltName: Full=Deoxyribonuclease I-like 3;
DE Short=DNase I-like 3;
DE Flags: Precursor;
GN Name=Dnase1l3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=9665719; DOI=10.1021/bi9800597;
RA Liu Q.Y., Pandey S., Singh R.K., Lin W., Ribecco M., Borowy-Borowski H.,
RA Smith B., Leblanc J., Walker P.R., Sikorska M.;
RT "DNaseY: a rat DNaseI-like gene coding for a constitutively expressed
RT chromatin-bound endonuclease.";
RL Biochemistry 37:10134-10143(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Spleen;
RX PubMed=9620874; DOI=10.1042/bj3320713;
RA Shiokawa D., Tanuma S.;
RT "Molecular cloning and expression of a cDNA encoding an apoptotic
RT endonuclease DNase gamma.";
RL Biochem. J. 332:713-720(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP PARTIAL PROTEIN SEQUENCE, AND CHARACTERIZATION.
RC TISSUE=Spleen;
RX PubMed=9328279; DOI=10.1006/abbi.1997.0275;
RA Shiokawa D., Iwamatsu A., Tanuma S.;
RT "Purification, characterization, and amino acid sequencing of DNase gamma
RT from rat spleen.";
RL Arch. Biochem. Biophys. 346:15-20(1997).
RN [5]
RP PARTIAL PROTEIN SEQUENCE, AND CHARACTERIZATION.
RX PubMed=9307016; DOI=10.1042/bj3260675;
RA Shiokawa D., Ohyama H., Yamada T., Tanuma S.;
RT "Purification and properties of DNase gamma from apoptotic rat
RT thymocytes.";
RL Biochem. J. 326:675-681(1997).
RN [6]
RP FUNCTION.
RC STRAIN=Sprague-Dawley; TISSUE=Spleen;
RX PubMed=7957253; DOI=10.1111/j.1432-1033.1994.tb20022.x;
RA Shiokawa D., Ohyama H., Yamada T., Takahashi K., Tanuma S.;
RT "Identification of an endonuclease responsible for apoptosis in rat
RT thymocytes.";
RL Eur. J. Biochem. 226:23-30(1994).
RN [7]
RP FUNCTION.
RX PubMed=15167901; DOI=10.1038/sj.cdd.4401454;
RA Shiokawa D., Tanuma S.;
RT "Differential DNases are selectively used in neuronal apoptosis depending
RT on the differentiation state.";
RL Cell Death Differ. 11:1112-1120(2004).
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 (PubMed:7957253). Can cleave chromatin to nucleosomal units and cleaves
CC nucleosomal and liposome-coated DNA. Acts in internucleosomal DNA
CC fragmentation (INDF) during apoptosis and necrosis. The role in
CC apoptosis includes myogenic and neuronal differentiation, and BCR-
CC mediated clonal deletion of self-reactive B cells. Is active on
CC chromatin in apoptotic cell-derived membrane-coated microparticles and
CC thus suppresses anti-DNA autoimmunity (By similarity). 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:Q13609,
CC ECO:0000269|PubMed:7957253}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:9665719};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:9665719};
CC -!- ACTIVITY REGULATION: Inhibited by zinc. {ECO:0000269|PubMed:9665719}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.2. Active from pH 6.0 to 9.0.
CC {ECO:0000269|PubMed:9665719};
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9665719}. Secreted
CC {ECO:0000250|UniProtKB:O55070, ECO:0000250|UniProtKB:Q13609}. Note=May
CC first pass through the ER membrane before being imported in the
CC nucleus. Contradictory reports exist about the subcellular localization
CC under normal physiological conditions. Under conditions of cell death,
CC may diffuse and/or be actively transported to the nucleus (By
CC similarity). {ECO:0000250|UniProtKB:O55070, ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Detected at high levels in spleen, lymph nodes,
CC thymus and liver. Observed also in kidney and testis, but not in brain
CC or heart.
CC -!- PTM: Seems to be synthesized as an inactive precursor protein and
CC converted into an active mature enzyme by removal of the N-terminal
CC precursor peptide during apoptosis.
CC -!- PTM: Poly-ADP-ribosylated by PARP1. ADP-ribosylation negatively
CC regulates enzymatic activity during apoptosis.
CC {ECO:0000250|UniProtKB:Q13609}.
CC -!- SIMILARITY: Belongs to the DNase I family. {ECO:0000305}.
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DR EMBL; AF039852; AAC28937.1; -; mRNA.
DR EMBL; U75689; AAC40134.1; -; mRNA.
DR EMBL; BC088122; AAH88122.1; -; mRNA.
DR RefSeq; NP_446359.1; NM_053907.1.
DR AlphaFoldDB; O89107; -.
DR SMR; O89107; -.
DR STRING; 10116.ENSRNOP00000012532; -.
DR PaxDb; O89107; -.
DR PRIDE; O89107; -.
DR Ensembl; ENSRNOT00000012532; ENSRNOP00000012532; ENSRNOG00000009291.
DR GeneID; 116687; -.
DR KEGG; rno:116687; -.
DR CTD; 1776; -.
DR RGD; 620669; Dnase1l3.
DR eggNOG; ENOG502QPNY; Eukaryota.
DR GeneTree; ENSGT00950000182846; -.
DR HOGENOM; CLU_043335_0_1_1; -.
DR InParanoid; O89107; -.
DR OMA; SRCDIML; -.
DR OrthoDB; 1282784at2759; -.
DR PhylomeDB; O89107; -.
DR TreeFam; TF329541; -.
DR PRO; PR:O89107; -.
DR Proteomes; UP000002494; Chromosome 15.
DR Bgee; ENSRNOG00000009291; Expressed in spleen and 17 other tissues.
DR Genevisible; O89107; RN.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0004530; F:deoxyribonuclease I activity; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IDA:RGD.
DR GO; GO:0004520; F:endodeoxyribonuclease activity; IDA:RGD.
DR GO; GO:0004519; F:endonuclease activity; ISO:RGD.
DR GO; GO:0006309; P:apoptotic DNA fragmentation; ISO:RGD.
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:0010623; P:programmed cell death involved in cell development; ISO:RGD.
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 ADP-ribosylation; Apoptosis; Calcium; Direct protein sequencing;
KW Disulfide bond; Endonuclease; Hydrolase; Nuclease; Nucleus;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..25
FT CHAIN 26..310
FT /note="Deoxyribonuclease gamma"
FT /id="PRO_0000007290"
FT REGION 289..310
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 40..56
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 301..307
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 105
FT /evidence="ECO:0000250|UniProtKB:P00639"
FT ACT_SITE 160
FT /evidence="ECO:0000250|UniProtKB:P00639"
FT DISULFID 199..236
FT /note="Essential for enzymatic activity"
FT /evidence="ECO:0000250|UniProtKB:O55070"
SQ SEQUENCE 310 AA; 35708 MW; 69C0E0874A3E9107 CRC64;
MSLYPASPYL ASLLLFILAL HGALSLRLCS FNVRSFGESK KENHNAMDII VKIIKRCDLI
LLMEIKDSNN NICPMLMEKL NGNSRRSTTY NYVISSRLGR NTYKEQYAFL YKEKLVSVKA
KYLYHDYQDG DTDVFSREPF VVWFQAPFTA AKDFVIVPLH TTPETSVKEI DELADVYTDV
RRRWKAENFI FMGDFNAGCS YVPKKAWKNI RLRTDPNFVW LIGDQEDTTV KKSTSCAYDR
IVLRGQEIVN SVVPRSSGVF DFQKAYELSE EEALDVSDHF PVEFKLQSSR AFTNSRKSVS
LKKKKKGSRS
