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Protein

Deoxyribonuclease gamma

Gene

Dnase1l3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Has DNA hydrolytic activity. Is capable of both single- and double-stranded DNA cleavage, producing DNA fragments with 3'-OH ends (By similarity). Can cleave chromatin to nucleosomal units and cleaves nucleosomal and liposome-coated DNA (PubMed:15796714, PubMed:19154352, PubMed:12095301). Acts in internucleosomal DNA fragmentation (INDF) during apoptosis and necrosis. The role in apoptosis includes myogenic and neuronal differentiation, and BCR-mediated clonal deletion of self-reactive B cells (PubMed:12050166, PubMed:15167901, PubMed:17218958, PubMed:24312463). Is active on chromatin in apoptotic cell-derived membrane-coated microparticles and thus suppresses anti-DNA autoimmunity (PubMed:15796714, PubMed:27293190). Together with DNASE1, plays a key role in degrading neutrophil extracellular traps (NETs) (PubMed:29191910). NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (PubMed:29191910). Degradation of intravascular NETs by DNASE1 and DNASE1L3 is required to prevent formation of clots that obstruct blood vessels and cause organ damage following inflammation (PubMed:29191910).By similarity1 Publication6 Publications

Cofactori

Protein has several cofactor binding sites:

Activity regulationi

Inhibited by zinc. Inhibited by heparin and proteolysis by plasmin.By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei105By similarity1
Active sitei160By similarity1

GO - Molecular functioni

  • deoxyribonuclease activity Source: GO_Central
  • deoxyribonuclease I activity Source: GO_Central
  • DNA binding Source: MGI
  • endodeoxyribonuclease activity Source: MGI
  • endonuclease activity Source: MGI

GO - Biological processi

Keywordsi

Molecular functionEndonuclease, Hydrolase, Nuclease
Biological processApoptosis, Necrosis
LigandCalcium

Enzyme and pathway databases

BRENDAi3.1.21.1 3474

Names & Taxonomyi

Protein namesi
Recommended name:
Deoxyribonuclease gamma (EC:3.1.21.-)
Short name:
DNase gamma
Alternative name(s):
DNase I homolog protein DHP2
Deoxyribonuclease I-like 3
Short name:
DNase I-like 3
Liver and spleen DNase
Short name:
LS-DNase
Short name:
LSD
Gene namesi
Name:Dnase1l3Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:1314633 Dnase1l3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endoplasmic reticulum, Nucleus, Secreted

Pathology & Biotechi

Disruption phenotypei

Mice develop symptoms of the autoimmune disease systemic lupus erythematosus, characterized by high titers of anti-nuclear autoantibodies (ANA) directed against nucleosomes and double-stranded DNA, the deposition of immune complexes in glomeruli and full-blown glomerulonephritis (PubMed:27293190). Mice lacking both Dnase1 and Dnase1l3 show vascular occlusions following bacterial infection: defects are caused by the formation of intravascular neutrophil extracellular traps (NETs) clots that obstruct blood vessels and cause organ damage (PubMed:29191910).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25By similarityAdd BLAST25
ChainiPRO_000000728926 – 310Deoxyribonuclease gammaAdd BLAST285

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi199 ↔ 236Essential for enzymatic activity1 Publication

Post-translational modificationi

Poly-ADP-ribosylated by PARP1. ADP-ribosylation negatively regulates enzymatic activity during apoptosis.By similarity

Keywords - PTMi

ADP-ribosylation, Disulfide bond

Proteomic databases

MaxQBiO55070
PaxDbiO55070
PRIDEiO55070

PTM databases

iPTMnetiO55070
PhosphoSitePlusiO55070

Expressioni

Tissue specificityi

Expressed at high levels in liver, spleen and testes. Expressed at lower levels in heart, lungs, skeletal muscle and kidney. Not expressed in brain. Predominantly expressed in macrophages; at protein level. Secreted by mononuclear phagocytes.4 Publications

Developmental stagei

Expression is first detected at embryonic day 11, and higher amounts were detected at days 15 and 17.1 Publication

Gene expression databases

BgeeiENSMUSG00000025279 Expressed in 43 organ(s), highest expression level in mesenteric lymph node
CleanExiMM_DNASE1L3
GenevisibleiO55070 MM

Structurei

3D structure databases

ProteinModelPortaliO55070
SMRiO55070
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni289 – 310Not required for free DNA-nuclease activity but required for activity towards liposome-coated DNA1 PublicationAdd BLAST22

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi40 – 56Bipartite nuclear localization signalSequence analysisAdd BLAST17
Motifi301 – 307Nuclear localization signalSequence analysis7

Sequence similaritiesi

Belongs to the DNase I family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IHHA Eukaryota
ENOG410ZR9A LUCA
GeneTreeiENSGT00390000013146
HOGENOMiHOG000059570
HOVERGENiHBG051368
InParanoidiO55070
KOiK11995
OMAiKIIKRCD
OrthoDBiEOG091G0I0B
PhylomeDBiO55070
TreeFamiTF329541

Family and domain databases

Gene3Di3.60.10.10, 1 hit
InterProiView protein in InterPro
IPR018057 Deoxyribonuclease-1_AS
IPR016202 DNase_I
IPR033125 DNASE_I_2
IPR036691 Endo/exonu/phosph_ase_sf
IPR005135 Endo/exonuclease/phosphatase
PfamiView protein in Pfam
PF03372 Exo_endo_phos, 1 hit
PIRSFiPIRSF000988 DNase_I_euk, 1 hit
PRINTSiPR00130 DNASEI
SMARTiView protein in SMART
SM00476 DNaseIc, 1 hit
SUPFAMiSSF56219 SSF56219, 1 hit
PROSITEiView protein in PROSITE
PS00919 DNASE_I_1, 1 hit
PS00918 DNASE_I_2, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O55070-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSLHPASPRL ASLLLFILAL HDTLALRLCS FNVRSFGASK KENHEAMDII
60 70 80 90 100
VKIIKRCDLI LLMEIKDSSN NICPMLMEKL NGNSRRSTTY NYVISSRLGR
110 120 130 140 150
NTYKEQYAFV YKEKLVSVKT KYHYHDYQDG DTDVFSREPF VVWFHSPFTA
160 170 180 190 200
VKDFVIVPLH TTPETSVKEI DELVDVYTDV RSQWKTENFI FMGDFNAGCS
210 220 230 240 250
YVPKKAWQNI RLRTDPKFVW LIGDQEDTTV KKSTSCAYDR IVLCGQEIVN
260 270 280 290 300
SVVPRSSGVF DFQKAYDLSE EEALDVSDHF PVEFKLQSSR AFTNNRKSVS
310
LKKRKKGNRS
Length:310
Mass (Da):35,760
Last modified:June 1, 1998 - v1
Checksum:iBE483821E045E374
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti89T → I in strain: DBA/2, NZB and NZW, in vitro decreases nuclease activity against free DNA by approximately twofold and decreases activity to establish a barrier to liposomal gene transfection by eightfold. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF047355 mRNA Translation: AAC35753.1
U76110 mRNA Translation: AAD09222.1
AY024355 Genomic DNA Translation: AAK07733.1
BC012671 mRNA Translation: AAH12671.1
CCDSiCCDS26807.1
RefSeqiNP_031896.3, NM_007870.3
XP_006517984.1, XM_006517921.3
UniGeneiMm.272258
Mm.490513

Genome annotation databases

EnsembliENSMUST00000026315; ENSMUSP00000026315; ENSMUSG00000025279
GeneIDi13421
KEGGimmu:13421
UCSCiuc007sem.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF047355 mRNA Translation: AAC35753.1
U76110 mRNA Translation: AAD09222.1
AY024355 Genomic DNA Translation: AAK07733.1
BC012671 mRNA Translation: AAH12671.1
CCDSiCCDS26807.1
RefSeqiNP_031896.3, NM_007870.3
XP_006517984.1, XM_006517921.3
UniGeneiMm.272258
Mm.490513

3D structure databases

ProteinModelPortaliO55070
SMRiO55070
ModBaseiSearch...
MobiDBiSearch...

PTM databases

iPTMnetiO55070
PhosphoSitePlusiO55070

Proteomic databases

MaxQBiO55070
PaxDbiO55070
PRIDEiO55070

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000026315; ENSMUSP00000026315; ENSMUSG00000025279
GeneIDi13421
KEGGimmu:13421
UCSCiuc007sem.1 mouse

Organism-specific databases

CTDi1776
MGIiMGI:1314633 Dnase1l3

Phylogenomic databases

eggNOGiENOG410IHHA Eukaryota
ENOG410ZR9A LUCA
GeneTreeiENSGT00390000013146
HOGENOMiHOG000059570
HOVERGENiHBG051368
InParanoidiO55070
KOiK11995
OMAiKIIKRCD
OrthoDBiEOG091G0I0B
PhylomeDBiO55070
TreeFamiTF329541

Enzyme and pathway databases

BRENDAi3.1.21.1 3474

Miscellaneous databases

PROiPR:O55070
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000025279 Expressed in 43 organ(s), highest expression level in mesenteric lymph node
CleanExiMM_DNASE1L3
GenevisibleiO55070 MM

Family and domain databases

Gene3Di3.60.10.10, 1 hit
InterProiView protein in InterPro
IPR018057 Deoxyribonuclease-1_AS
IPR016202 DNase_I
IPR033125 DNASE_I_2
IPR036691 Endo/exonu/phosph_ase_sf
IPR005135 Endo/exonuclease/phosphatase
PfamiView protein in Pfam
PF03372 Exo_endo_phos, 1 hit
PIRSFiPIRSF000988 DNase_I_euk, 1 hit
PRINTSiPR00130 DNASEI
SMARTiView protein in SMART
SM00476 DNaseIc, 1 hit
SUPFAMiSSF56219 SSF56219, 1 hit
PROSITEiView protein in PROSITE
PS00919 DNASE_I_1, 1 hit
PS00918 DNASE_I_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDNSL3_MOUSE
AccessioniPrimary (citable) accession number: O55070
Secondary accession number(s): Q91X38
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: June 1, 1998
Last modified: November 7, 2018
This is version 141 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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