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Protein

Deoxyribonuclease gamma

Gene

DNASE1L3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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:9070308, PubMed:9714828, PubMed:14646506, PubMed:10807908, PubMed:27293190). Acts in internucleosomal DNA fragmentation (INDF) during apoptosis and necrosis (PubMed:23229555, PubMed:24312463). The role in apoptosis includes myogenic and neuronal differentiation, and BCR-mediated clonal deletion of self-reactive B cells (By similarity). Is active on chromatin in apoptotic cell-derived membrane-coated microparticles and thus suppresses anti-DNA autoimmunity (PubMed:27293190).By similarity7 Publications

Cofactori

Protein has several cofactor binding sites:

Enzyme regulationi

Inhibited by zinc.By similarity

pH dependencei

Optimum pH is about 7.2.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei100By similarity1
Active sitei155By similarity1

GO - Molecular functioni

  • calcium ion binding Source: ProtInc
  • deoxyribonuclease activity Source: ProtInc
  • DNA binding Source: ProtInc
  • endodeoxyribonuclease activity Source: Ensembl

GO - Biological processi

  • apoptotic DNA fragmentation Source: UniProtKB
  • DNA metabolic process Source: ProtInc
  • programmed cell death involved in cell development Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Endonuclease, Hydrolase, Nuclease

Keywords - Biological processi

Apoptosis, Necrosis

Keywords - Ligandi

Calcium

Enzyme and pathway databases

BioCyciZFISH:HS08914-MONOMER.

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:DNASE1L3
Synonyms:DHP2, DNAS1L3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:2959. DNASE1L3.

Subcellular locationi

GO - Cellular componenti

  • endoplasmic reticulum Source: UniProtKB
  • extracellular region Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Nucleus, Secreted

Pathology & Biotechi

Involvement in diseasei

Systemic lupus erythematosus 16 (SLEB16)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare autosomal recessive form of systemic lupus erythematosus with childhood onset, characterized by high frequency of anti-neutrophil cytoplasmic antibodies and lupus nephritis. Systemic lupus erythematosus is a chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
See also OMIM:614420

Keywords - Diseasei

Systemic lupus erythematosus

Organism-specific databases

DisGeNETi1776.
MalaCardsiDNASE1L3.
MIMi614420. phenotype.
OpenTargetsiENSG00000163687.
Orphaneti300345. Autosomal recessive systemic lupus erythematosus.
36412. Hypocomplementemic urticarial vasculitis.
PharmGKBiPA27430.

Chemistry databases

ChEMBLiCHEMBL1649048.

Polymorphism and mutation databases

BioMutaiDNASE1L3.
DMDMi2494173.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20By similarityAdd BLAST20
ChainiPRO_000000728821 – 305Deoxyribonuclease gammaAdd BLAST285

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi194 ↔ 231Essential for enzymatic activityBy similarity

Post-translational modificationi

Poly-ADP-ribosylated by PARP1. ADP-ribosylation negatively regulates enzymatic activity during apoptosis.1 Publication

Keywords - PTMi

ADP-ribosylation, Disulfide bond

Proteomic databases

PaxDbiQ13609.
PeptideAtlasiQ13609.
PRIDEiQ13609.

PTM databases

iPTMnetiQ13609.
PhosphoSitePlusiQ13609.

Expressioni

Tissue specificityi

Liver and spleen.

Gene expression databases

BgeeiENSG00000163687.
CleanExiHS_DNASE1L3.
ExpressionAtlasiQ13609. baseline and differential.
GenevisibleiQ13609. HS.

Organism-specific databases

HPAiHPA019955.

Interactioni

Protein-protein interaction databases

IntActiQ13609. 2 interactors.
MINTiMINT-4723961.
STRINGi9606.ENSP00000316193.

Chemistry databases

BindingDBiQ13609.

Structurei

3D structure databases

ProteinModelPortaliQ13609.
SMRiQ13609.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni284 – 305Not required for free DNA-nuclease activity but required for activity towards liposome-coated DNABy similarityAdd BLAST22

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi35 – 51Bipartite nuclear localization signalSequence analysisAdd BLAST17
Motifi296 – 304Nuclear localization signalSequence analysis9

Sequence similaritiesi

Belongs to the DNase I family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IHHA. Eukaryota.
ENOG410ZR9A. LUCA.
GeneTreeiENSGT00390000013146.
HOGENOMiHOG000059570.
HOVERGENiHBG051368.
InParanoidiQ13609.
KOiK11995.
OMAiQSPHTAV.
OrthoDBiEOG091G0I0B.
PhylomeDBiQ13609.
TreeFamiTF329541.

Family and domain databases

Gene3Di3.60.10.10. 1 hit.
InterProiIPR018057. Deoxyribonuclease-1_AS.
IPR016202. DNase_I.
IPR033125. DNASE_I_2.
IPR005135. Endo/exonuclease/phosphatase.
[Graphical view]
PANTHERiPTHR11371. PTHR11371. 1 hit.
PfamiPF03372. Exo_endo_phos. 1 hit.
[Graphical view]
PIRSFiPIRSF000988. DNase_I_euk. 1 hit.
PRINTSiPR00130. DNASEI.
SMARTiSM00476. DNaseIc. 1 hit.
[Graphical view]
SUPFAMiSSF56219. SSF56219. 1 hit.
PROSITEiPS00919. DNASE_I_1. 1 hit.
PS00918. DNASE_I_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13609-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSRELAPLLL LLLSIHSALA MRICSFNVRS FGESKQEDKN AMDVIVKVIK
60 70 80 90 100
RCDIILVMEI KDSNNRICPI LMEKLNRNSR RGITYNYVIS SRLGRNTYKE
110 120 130 140 150
QYAFLYKEKL VSVKRSYHYH DYQDGDADVF SREPFVVWFQ SPHTAVKDFV
160 170 180 190 200
IIPLHTTPET SVKEIDELVE VYTDVKHRWK AENFIFMGDF NAGCSYVPKK
210 220 230 240 250
AWKNIRLRTD PRFVWLIGDQ EDTTVKKSTN CAYDRIVLRG QEIVSSVVPK
260 270 280 290 300
SNSVFDFQKA YKLTEEEALD VSDHFPVEFK LQSSRAFTNS KKSVTLRKKT

KSKRS
Length:305
Mass (Da):35,504
Last modified:November 1, 1997 - v1
Checksum:iBAB9F1A0341E6048
GO
Isoform 2 (identifier: Q13609-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     78-107: Missing.

Note: Gene prediction based on EST data.
Show »
Length:275
Mass (Da):31,860
Checksum:i98690E78ED2EC18C
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03607919L → V in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs763778721dbSNPEnsembl.1
Natural variantiVAR_03608082G → R in a breast cancer sample; somatic mutation, diminishes enzymatic activity. 2 PublicationsCorresponds to variant rs74350392dbSNPEnsembl.1
Natural variantiVAR_05924996N → K.1 PublicationCorresponds to variant rs12491947dbSNPEnsembl.1
Natural variantiVAR_036081117Y → S in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_076797206R → C Abolishes enzymatic activity. 3 PublicationsCorresponds to variant rs35677470dbSNPEnsembl.1
Natural variantiVAR_061137243I → M.1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04725178 – 107Missing in isoform 2. 1 PublicationAdd BLAST30

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U56814 mRNA. Translation: AAB63967.1.
AF047354 mRNA. Translation: AAC35752.1.
U75744 mRNA. Translation: AAC23652.1.
AK301263 mRNA. Translation: BAH13443.1.
AK313303 mRNA. Translation: BAG36108.1.
AC137936 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW65358.1.
BC015831 mRNA. Translation: AAH15831.1.
CCDSiCCDS2886.1. [Q13609-1]
CCDS58836.1. [Q13609-2]
PIRiJC5361.
RefSeqiNP_001243489.1. NM_001256560.1. [Q13609-2]
NP_004935.1. NM_004944.3. [Q13609-1]
UniGeneiHs.476453.

Genome annotation databases

EnsembliENST00000394549; ENSP00000378053; ENSG00000163687. [Q13609-1]
ENST00000486455; ENSP00000419052; ENSG00000163687. [Q13609-2]
GeneIDi1776.
KEGGihsa:1776.
UCSCiuc003djo.3. human. [Q13609-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U56814 mRNA. Translation: AAB63967.1.
AF047354 mRNA. Translation: AAC35752.1.
U75744 mRNA. Translation: AAC23652.1.
AK301263 mRNA. Translation: BAH13443.1.
AK313303 mRNA. Translation: BAG36108.1.
AC137936 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW65358.1.
BC015831 mRNA. Translation: AAH15831.1.
CCDSiCCDS2886.1. [Q13609-1]
CCDS58836.1. [Q13609-2]
PIRiJC5361.
RefSeqiNP_001243489.1. NM_001256560.1. [Q13609-2]
NP_004935.1. NM_004944.3. [Q13609-1]
UniGeneiHs.476453.

3D structure databases

ProteinModelPortaliQ13609.
SMRiQ13609.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ13609. 2 interactors.
MINTiMINT-4723961.
STRINGi9606.ENSP00000316193.

Chemistry databases

BindingDBiQ13609.
ChEMBLiCHEMBL1649048.

PTM databases

iPTMnetiQ13609.
PhosphoSitePlusiQ13609.

Polymorphism and mutation databases

BioMutaiDNASE1L3.
DMDMi2494173.

Proteomic databases

PaxDbiQ13609.
PeptideAtlasiQ13609.
PRIDEiQ13609.

Protocols and materials databases

DNASUi1776.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000394549; ENSP00000378053; ENSG00000163687. [Q13609-1]
ENST00000486455; ENSP00000419052; ENSG00000163687. [Q13609-2]
GeneIDi1776.
KEGGihsa:1776.
UCSCiuc003djo.3. human. [Q13609-1]

Organism-specific databases

CTDi1776.
DisGeNETi1776.
GeneCardsiDNASE1L3.
HGNCiHGNC:2959. DNASE1L3.
HPAiHPA019955.
MalaCardsiDNASE1L3.
MIMi602244. gene.
614420. phenotype.
neXtProtiNX_Q13609.
OpenTargetsiENSG00000163687.
Orphaneti300345. Autosomal recessive systemic lupus erythematosus.
36412. Hypocomplementemic urticarial vasculitis.
PharmGKBiPA27430.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IHHA. Eukaryota.
ENOG410ZR9A. LUCA.
GeneTreeiENSGT00390000013146.
HOGENOMiHOG000059570.
HOVERGENiHBG051368.
InParanoidiQ13609.
KOiK11995.
OMAiQSPHTAV.
OrthoDBiEOG091G0I0B.
PhylomeDBiQ13609.
TreeFamiTF329541.

Enzyme and pathway databases

BioCyciZFISH:HS08914-MONOMER.

Miscellaneous databases

ChiTaRSiDNASE1L3. human.
GeneWikiiDNASE1L3.
GenomeRNAii1776.
PROiQ13609.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163687.
CleanExiHS_DNASE1L3.
ExpressionAtlasiQ13609. baseline and differential.
GenevisibleiQ13609. HS.

Family and domain databases

Gene3Di3.60.10.10. 1 hit.
InterProiIPR018057. Deoxyribonuclease-1_AS.
IPR016202. DNase_I.
IPR033125. DNASE_I_2.
IPR005135. Endo/exonuclease/phosphatase.
[Graphical view]
PANTHERiPTHR11371. PTHR11371. 1 hit.
PfamiPF03372. Exo_endo_phos. 1 hit.
[Graphical view]
PIRSFiPIRSF000988. DNase_I_euk. 1 hit.
PRINTSiPR00130. DNASEI.
SMARTiSM00476. DNaseIc. 1 hit.
[Graphical view]
SUPFAMiSSF56219. SSF56219. 1 hit.
PROSITEiPS00919. DNASE_I_1. 1 hit.
PS00918. DNASE_I_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDNSL3_HUMAN
AccessioniPrimary (citable) accession number: Q13609
Secondary accession number(s): B2R8B1, B7Z707, O75803
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: November 30, 2016
This is version 159 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.