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Protein

Deoxyribonuclease-1

Gene

DNASE1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Serum endocuclease secreted into body fluids by a wide variety of exocrine and endocrine organs (PubMed:2251263, PubMed:11241278, PubMed:2277032). Expressed by non-hematopoietic tissues and preferentially cleaves protein-free DNA (By similarity). Among other functions, seems to be involved in cell death by apoptosis (PubMed:11241278). Binds specifically to G-actin and blocks actin polymerization (By similarity). Together with DNASE1L3, plays a key role in degrading neutrophil extracellular traps (NETs) (By similarity). NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (By similarity). 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 (By similarity).By similarity3 Publications

Catalytic activityi

Endonucleolytic cleavage to 5'-phosphodinucleotide and 5'-phosphooligonucleotide end-products.3 Publications

Cofactori

Ca2+2 Publications, Mg2+2 PublicationsNote: Divalent metal cations. Prefers Ca2+ or Mg2+.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei35Involved in actin-bindingBy similarity1
Sitei87Nitration by tetranitromethane destroys a Ca(2+) binding site and inactivates enzymeBy similarity1
Sitei89Involved in actin-bindingBy similarity1
Active sitei100By similarity1
Active sitei156By similarity1

GO - Molecular functioni

  • actin binding Source: UniProtKB-KW
  • deoxyribonuclease activity Source: GO_Central
  • deoxyribonuclease I activity Source: GO_Central
  • DNA binding Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionActin-binding, Endonuclease, Hydrolase, Nuclease
Biological processApoptosis
LigandCalcium

Enzyme and pathway databases

BRENDAi3.1.21.1 2681
SIGNORiP24855

Names & Taxonomyi

Protein namesi
Recommended name:
Deoxyribonuclease-1 (EC:3.1.21.13 Publications)
Alternative name(s):
Deoxyribonuclease I
Short name:
DNase I
INN: Dornase alfa
Gene namesi
Name:DNASE1Imported
Synonyms:DNL1, DRNI
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000213918.10
HGNCiHGNC:2956 DNASE1
MIMi125505 gene
neXtProtiNX_P24855

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

Nucleus, Secreted

Pathology & Biotechi

Involvement in diseasei

Systemic lupus erythematosus (SLE)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry. Neutrophil extracellular traps (NETs) are impaired in patients suffering from SLE (PubMed:20439745). NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (PubMed:20439745).1 Publication
Disease descriptionA 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:152700

Pharmaceutical usei

Available under the name Pulmozyme (Genentech). Used to reduce the viscosity of cystic fibrosis sputum by hydrolyzing the extracellular DNA released by degenerating leukocytes that accumulate in response to infection.1 Publication

Keywords - Diseasei

Systemic lupus erythematosus

Organism-specific databases

DisGeNETi1773
MalaCardsiDNASE1
MIMi152700 phenotype
OpenTargetsiENSG00000213918
Orphaneti300345 Autosomal systemic lupus erythematosus
536 NON RARE IN EUROPE: Systemic lupus erythematosus
PharmGKBiPA27427

Chemistry databases

ChEMBLiCHEMBL3351219

Polymorphism and mutation databases

BioMutaiDNASE1
DMDMi118919

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 222 PublicationsAdd BLAST22
ChainiPRO_000000727723 – 282Deoxyribonuclease-1Add BLAST260

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi40N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi123 ↔ 126By similarity
Glycosylationi128N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi195 ↔ 231Essential for enzymatic activityBy similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP24855
PeptideAtlasiP24855
PRIDEiP24855
ProteomicsDBi54233

PTM databases

iPTMnetiP24855
PhosphoSitePlusiP24855

Expressioni

Tissue specificityi

Principally in tissues of the digestive system. Highest levels found in urine, but also relatively abundant in semen and saliva.

Gene expression databases

BgeeiENSG00000213918 Expressed in 174 organ(s), highest expression level in cortex of kidney
CleanExiHS_DNASE1
ExpressionAtlasiP24855 baseline and differential
GenevisibleiP24855 HS

Organism-specific databases

HPAiHPA010703

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108112, 2 interactors
STRINGi9606.ENSP00000246949

Chemistry databases

BindingDBiP24855

Structurei

Secondary structure

1282
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP24855
SMRiP24855
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the DNase I family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IFZB Eukaryota
ENOG410Z4MV LUCA
GeneTreeiENSGT00390000013146
HOGENOMiHOG000059570
HOVERGENiHBG051368
InParanoidiP24855
KOiK11994
OMAiSHWSSIR
OrthoDBiEOG091G0I0B
PhylomeDBiP24855
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

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

This entry has 2 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P24855-1) [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
MRGMKLLGAL LALAALLQGA VSLKIAAFNI QTFGETKMSN ATLVSYIVQI
60 70 80 90 100
LSRYDIALVQ EVRDSHLTAV GKLLDNLNQD APDTYHYVVS EPLGRNSYKE
110 120 130 140 150
RYLFVYRPDQ VSAVDSYYYD DGCEPCGNDT FNREPAIVRF FSRFTEVREF
160 170 180 190 200
AIVPLHAAPG DAVAEIDALY DVYLDVQEKW GLEDVMLMGD FNAGCSYVRP
210 220 230 240 250
SQWSSIRLWT SPTFQWLIPD SADTTATPTH CAYDRIVVAG MLLRGAVVPD
260 270 280
SALPFNFQAA YGLSDQLAQA ISDHYPVEVM LK
Length:282
Mass (Da):31,434
Last modified:March 1, 1992 - v1
Checksum:i040042E2D23555B6
GO
Isoform 2 (identifier: P24855-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-66: MRGMKLLGAL...ALVQEVRDSH → MHQTPITTWS...PLSGSSPGSQ
     67-183: Missing.
     268-282: AQAISDHYPVEVMLK → FSVHTCSGAGLGERHGLPASAALPSNTCRAGTHRVST

Note: No experimental confirmation available.
Show »
Length:187
Mass (Da):19,771
Checksum:iC66A988635746FB9
GO

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
I3L0Z9I3L0Z9_HUMAN
Deoxyribonuclease-1
DNASE1
86Annotation score:
I3L298I3L298_HUMAN
Deoxyribonuclease-1
DNASE1
108Annotation score:
I3L1N2I3L1N2_HUMAN
Deoxyribonuclease-1
DNASE1
90Annotation score:
I3L4B8I3L4B8_HUMAN
Deoxyribonuclease-1
DNASE1
72Annotation score:
I3L4C7I3L4C7_HUMAN
Deoxyribonuclease-1
DNASE1
65Annotation score:
I3L530I3L530_HUMAN
Deoxyribonuclease-1
DNASE1
60Annotation score:
I3L4U3I3L4U3_HUMAN
Deoxyribonuclease-1
DNASE1
75Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti143R → Q in BAE96964 (PubMed:16771825).Curated1

Polymorphismi

At least 6 alleles of DNASE1 are known: DNASE1*1 to DNASE1*6. The sequence shown is that of DNASE1*2.4 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0244342R → S. Corresponds to variant dbSNP:rs8176927Ensembl.1
Natural variantiVAR_00226431Q → E in allele DNASE1*4. Corresponds to variant dbSNP:rs77254040Ensembl.1
Natural variantiVAR_029172107R → G. Corresponds to variant dbSNP:rs8176928Ensembl.1
Natural variantiVAR_009300114V → M in allele DNASE1*5. Corresponds to variant dbSNP:rs530214101Ensembl.1
Natural variantiVAR_024435127G → R. Corresponds to variant dbSNP:rs8176919Ensembl.1
Natural variantiVAR_002265154P → A in allele DNASE1*3. Corresponds to variant dbSNP:rs1799891Ensembl.1
Natural variantiVAR_009301207R → C in allele DNASE1*6. Corresponds to variant dbSNP:rs148373909EnsemblClinVar.1
Natural variantiVAR_029173231C → Y. Corresponds to variant dbSNP:rs8176940Ensembl.1
Natural variantiVAR_002266244R → Q in allele DNASE1*1. 1 PublicationCorresponds to variant dbSNP:rs1053874EnsemblClinVar.1
Natural variantiVAR_029174246A → P. Corresponds to variant dbSNP:rs8176939Ensembl.1
Natural variantiVAR_029175262G → D. Corresponds to variant dbSNP:rs8176924Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0569741 – 66MRGMK…VRDSH → MHQTPITTWSVSHWDGTAIR SATCSCTGLTRCLRWTATTT MMAASPAGTTPSTESQPLSG SSPGSQ in isoform 2. 1 PublicationAdd BLAST66
Alternative sequenceiVSP_05697567 – 183Missing in isoform 2. 1 PublicationAdd BLAST117
Alternative sequenceiVSP_056976268 – 282AQAIS…EVMLK → FSVHTCSGAGLGERHGLPAS AALPSNTCRAGTHRVST in isoform 2. 1 PublicationAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M55983 mRNA Translation: AAA63170.1
D83195 Genomic DNA Translation: BAA11841.1
AJ298844 mRNA Translation: CAC12813.1
AB188151 mRNA Translation: BAE96964.1
AB188152 mRNA Translation: BAE96965.1
AK300914 mRNA Translation: BAG62547.1
AC005203 Genomic DNA Translation: AAC24721.1
AC006111 Genomic DNA No translation available.
CH471112 Genomic DNA Translation: EAW85344.1
BC029437 mRNA Translation: AAH29437.1
CCDSiCCDS10507.1 [P24855-1]
PIRiA38417 NDHU1
RefSeqiNP_005214.2, NM_005223.3 [P24855-1]
XP_011520695.1, XM_011522393.2 [P24855-1]
XP_016878488.1, XM_017022999.1
XP_016878492.1, XM_017023003.1 [P24855-2]
XP_016878493.1, XM_017023004.1 [P24855-2]
XP_016878494.1, XM_017023005.1 [P24855-2]
XP_016878495.1, XM_017023006.1 [P24855-2]
UniGeneiHs.629638
Hs.733045

Genome annotation databases

EnsembliENST00000246949; ENSP00000246949; ENSG00000213918 [P24855-1]
ENST00000407479; ENSP00000385905; ENSG00000213918 [P24855-1]
GeneIDi1773
KEGGihsa:1773
UCSCiuc002cvr.4 human [P24855-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Pulmozyme

Clinical information on Pulmozyme

Wikipedia

Deoxyribonuclease entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M55983 mRNA Translation: AAA63170.1
D83195 Genomic DNA Translation: BAA11841.1
AJ298844 mRNA Translation: CAC12813.1
AB188151 mRNA Translation: BAE96964.1
AB188152 mRNA Translation: BAE96965.1
AK300914 mRNA Translation: BAG62547.1
AC005203 Genomic DNA Translation: AAC24721.1
AC006111 Genomic DNA No translation available.
CH471112 Genomic DNA Translation: EAW85344.1
BC029437 mRNA Translation: AAH29437.1
CCDSiCCDS10507.1 [P24855-1]
PIRiA38417 NDHU1
RefSeqiNP_005214.2, NM_005223.3 [P24855-1]
XP_011520695.1, XM_011522393.2 [P24855-1]
XP_016878488.1, XM_017022999.1
XP_016878492.1, XM_017023003.1 [P24855-2]
XP_016878493.1, XM_017023004.1 [P24855-2]
XP_016878494.1, XM_017023005.1 [P24855-2]
XP_016878495.1, XM_017023006.1 [P24855-2]
UniGeneiHs.629638
Hs.733045

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4AWNX-ray1.95A23-282[»]
ProteinModelPortaliP24855
SMRiP24855
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108112, 2 interactors
STRINGi9606.ENSP00000246949

Chemistry databases

BindingDBiP24855
ChEMBLiCHEMBL3351219

PTM databases

iPTMnetiP24855
PhosphoSitePlusiP24855

Polymorphism and mutation databases

BioMutaiDNASE1
DMDMi118919

Proteomic databases

PaxDbiP24855
PeptideAtlasiP24855
PRIDEiP24855
ProteomicsDBi54233

Protocols and materials databases

DNASUi1773
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000246949; ENSP00000246949; ENSG00000213918 [P24855-1]
ENST00000407479; ENSP00000385905; ENSG00000213918 [P24855-1]
GeneIDi1773
KEGGihsa:1773
UCSCiuc002cvr.4 human [P24855-1]

Organism-specific databases

CTDi1773
DisGeNETi1773
EuPathDBiHostDB:ENSG00000213918.10
GeneCardsiDNASE1
HGNCiHGNC:2956 DNASE1
HPAiHPA010703
MalaCardsiDNASE1
MIMi125505 gene
152700 phenotype
neXtProtiNX_P24855
OpenTargetsiENSG00000213918
Orphaneti300345 Autosomal systemic lupus erythematosus
536 NON RARE IN EUROPE: Systemic lupus erythematosus
PharmGKBiPA27427
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFZB Eukaryota
ENOG410Z4MV LUCA
GeneTreeiENSGT00390000013146
HOGENOMiHOG000059570
HOVERGENiHBG051368
InParanoidiP24855
KOiK11994
OMAiSHWSSIR
OrthoDBiEOG091G0I0B
PhylomeDBiP24855
TreeFamiTF329541

Enzyme and pathway databases

BRENDAi3.1.21.1 2681
SIGNORiP24855

Miscellaneous databases

ChiTaRSiDNASE1 human
GeneWikiiDeoxyribonuclease_I
GenomeRNAii1773
PROiPR:P24855
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000213918 Expressed in 174 organ(s), highest expression level in cortex of kidney
CleanExiHS_DNASE1
ExpressionAtlasiP24855 baseline and differential
GenevisibleiP24855 HS

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 nameiDNAS1_HUMAN
AccessioniPrimary (citable) accession number: P24855
Secondary accession number(s): B4DV35, Q14UU9, Q14UV0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: March 1, 1992
Last modified: November 7, 2018
This is version 191 of the entry and version 1 of the sequence. See 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

3D-structure, Complete proteome, Direct protein sequencing, Pharmaceutical, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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