UniProtKB - P24855 (DNAS1_HUMAN)
Protein
Deoxyribonuclease-1
Gene
DNASE1
Organism
Homo sapiens (Human)
Status
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 EC:3.1.21.1
Cofactori
Ca2+2 Publications, Mg2+2 PublicationsNote: Divalent metal cations. Prefers Ca2+ or Mg2+.2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 35 | Involved in actin-bindingBy similarity | 1 | |
Sitei | 87 | Nitration by tetranitromethane destroys a Ca(2+) binding site and inactivates enzymeBy similarity | 1 | |
Sitei | 89 | Involved in actin-bindingBy similarity | 1 | |
Active sitei | 100 | By similarity | 1 | |
Active sitei | 156 | By similarity | 1 |
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
- apoptotic process Source: UniProtKB-KW
- DNA catabolic process Source: GO_Central
- DNA catabolic process, endonucleolytic Source: UniProtKB
- neutrophil activation involved in immune response Source: UniProtKB
- regulation of acute inflammatory response Source: UniProtKB
- regulation of neutrophil mediated cytotoxicity Source: UniProtKB
Keywordsi
Molecular function | Actin-binding, Endonuclease, Hydrolase, Nuclease |
Biological process | Apoptosis |
Ligand | Calcium |
Enzyme and pathway databases
BRENDAi | 3.1.21.1, 2681 |
PathwayCommonsi | P24855 |
SIGNORi | P24855 |
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 | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:2956, DNASE1 |
MIMi | 125505, gene |
neXtProti | NX_P24855 |
VEuPathDBi | HostDB:ENSG00000213918.10 |
Subcellular locationi
Extracellular region or secreted
- Secreted 1 Publication
Nucleus
Note: Secretory protein, stored in zymogen granules and found in the nuclear envelope.
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular region Source: ProtInc
Nucleus
- nuclear envelope Source: UniProtKB-SubCell
- nucleus Source: GO_Central
Keywords - Cellular componenti
Nucleus, SecretedPathology & Biotechi
Involvement in diseasei
Systemic lupus erythematosus (SLE)2 Publications
Disease susceptibility is associated with variants 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.
Related information in OMIMPharmaceutical 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 erythematosusOrganism-specific databases
DisGeNETi | 1773 |
MalaCardsi | DNASE1 |
MIMi | 152700, phenotype |
OpenTargetsi | ENSG00000213918 |
Orphaneti | 300345, Autosomal systemic lupus erythematosus 536, Systemic lupus erythematosus |
PharmGKBi | PA27427 |
Miscellaneous databases
Pharosi | P24855, Tchem |
Chemistry databases
ChEMBLi | CHEMBL3351219 |
Genetic variation databases
BioMutai | DNASE1 |
DMDMi | 118919 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 22 | 2 PublicationsAdd BLAST | 22 | |
ChainiPRO_0000007277 | 23 – 282 | Deoxyribonuclease-1Add BLAST | 260 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 40 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 123 ↔ 126 | By similarity | ||
Glycosylationi | 128 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 195 ↔ 231 | Essential for enzymatic activityBy similarity |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
jPOSTi | P24855 |
MassIVEi | P24855 |
PaxDbi | P24855 |
PeptideAtlasi | P24855 |
PRIDEi | P24855 |
ProteomicsDBi | 5238 54233 [P24855-1] |
PTM databases
GlyConnecti | 2005, 1 N-Linked glycan (1 site) |
GlyGeni | P24855, 2 sites |
iPTMneti | P24855 |
PhosphoSitePlusi | P24855 |
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
Bgeei | ENSG00000213918, Expressed in pancreas and 192 other tissues |
ExpressionAtlasi | P24855, baseline and differential |
Genevisiblei | P24855, HS |
Organism-specific databases
HPAi | ENSG00000213918, Tissue enhanced (intestine) |
Interactioni
GO - Molecular functioni
- actin binding Source: UniProtKB-KW
Protein-protein interaction databases
BioGRIDi | 108112, 2 interactors |
STRINGi | 9606.ENSP00000385905 |
Chemistry databases
BindingDBi | P24855 |
Miscellaneous databases
RNActi | P24855, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P24855 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Sequence similaritiesi
Belongs to the DNase I family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG502QQFT, Eukaryota |
GeneTreei | ENSGT00950000182846 |
HOGENOMi | CLU_043335_2_1_1 |
InParanoidi | P24855 |
OMAi | FSCPFTE |
OrthoDBi | 1282784at2759 |
PhylomeDBi | P24855 |
TreeFami | TF329541 |
Family and domain databases
Gene3Di | 3.60.10.10, 1 hit |
InterProi | View protein in InterPro IPR018057, Deoxyribonuclease-1_AS IPR016202, DNase_I IPR033125, DNASE_I_2 IPR036691, Endo/exonu/phosph_ase_sf IPR005135, Endo/exonuclease/phosphatase |
Pfami | View protein in Pfam PF03372, Exo_endo_phos, 1 hit |
PIRSFi | PIRSF000988, DNase_I_euk, 1 hit |
PRINTSi | PR00130, DNASEI |
SMARTi | View protein in SMART SM00476, DNaseIc, 1 hit |
SUPFAMi | SSF56219, SSF56219, 1 hit |
PROSITEi | View protein in PROSITE PS00919, DNASE_I_1, 1 hit PS00918, DNASE_I_2, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis 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 sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketI3L0Z9 | I3L0Z9_HUMAN | Deoxyribonuclease-1 | DNASE1 | 86 | Annotation score: | ||
I3L298 | I3L298_HUMAN | Deoxyribonuclease-1 | DNASE1 | 108 | Annotation score: | ||
I3L4B8 | I3L4B8_HUMAN | Deoxyribonuclease-1 | DNASE1 | 72 | Annotation score: | ||
I3L1N2 | I3L1N2_HUMAN | Deoxyribonuclease-1 | DNASE1 | 90 | Annotation score: | ||
I3L4C7 | I3L4C7_HUMAN | Deoxyribonuclease-1 | DNASE1 | 65 | Annotation score: | ||
I3L530 | I3L530_HUMAN | Deoxyribonuclease-1 | DNASE1 | 60 | Annotation score: | ||
I3L4U3 | I3L4U3_HUMAN | Deoxyribonuclease-1 | DNASE1 | 75 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 143 | R → Q in BAE96964 (PubMed:16771825).Curated | 1 |
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_024434 | 2 | R → S. Corresponds to variant dbSNP:rs8176927Ensembl. | 1 | |
Natural variantiVAR_002264 | 31 | Q → E in allele DNASE1*4. Corresponds to variant dbSNP:rs77254040Ensembl. | 1 | |
Natural variantiVAR_029172 | 107 | R → G. Corresponds to variant dbSNP:rs8176928Ensembl. | 1 | |
Natural variantiVAR_009300 | 114 | V → M in allele DNASE1*5. Corresponds to variant dbSNP:rs530214101Ensembl. | 1 | |
Natural variantiVAR_024435 | 127 | G → R. Corresponds to variant dbSNP:rs8176919Ensembl. | 1 | |
Natural variantiVAR_002265 | 154 | P → A in allele DNASE1*3. Corresponds to variant dbSNP:rs1799891Ensembl. | 1 | |
Natural variantiVAR_009301 | 207 | R → C in allele DNASE1*6. Corresponds to variant dbSNP:rs148373909EnsemblClinVar. | 1 | |
Natural variantiVAR_029173 | 231 | C → Y. Corresponds to variant dbSNP:rs8176940Ensembl. | 1 | |
Natural variantiVAR_002266 | 244 | R → Q in allele DNASE1*1. 1 PublicationCorresponds to variant dbSNP:rs1053874EnsemblClinVar. | 1 | |
Natural variantiVAR_029174 | 246 | A → P. Corresponds to variant dbSNP:rs8176939Ensembl. | 1 | |
Natural variantiVAR_029175 | 262 | G → D. Corresponds to variant dbSNP:rs8176924Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_056974 | 1 – 66 | MRGMK…VRDSH → MHQTPITTWSVSHWDGTAIR SATCSCTGLTRCLRWTATTT MMAASPAGTTPSTESQPLSG SSPGSQ in isoform 2. 1 PublicationAdd BLAST | 66 | |
Alternative sequenceiVSP_056975 | 67 – 183 | Missing in isoform 2. 1 PublicationAdd BLAST | 117 | |
Alternative sequenceiVSP_056976 | 268 – 282 | AQAIS…EVMLK → FSVHTCSGAGLGERHGLPAS AALPSNTCRAGTHRVST in isoform 2. 1 PublicationAdd BLAST | 15 |
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 |
CCDSi | CCDS10507.1 [P24855-1] |
PIRi | A38417, NDHU1 |
RefSeqi | NP_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] |
Genome annotation databases
Ensembli | ENST00000246949; ENSP00000246949; ENSG00000213918 [P24855-1] ENST00000407479; ENSP00000385905; ENSG00000213918 [P24855-1] |
GeneIDi | 1773 |
KEGGi | hsa:1773 |
UCSCi | uc002cvr.4, human [P24855-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar 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 |
CCDSi | CCDS10507.1 [P24855-1] |
PIRi | A38417, NDHU1 |
RefSeqi | NP_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] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4AWN | X-ray | 1.95 | A | 23-282 | [»] | |
SMRi | P24855 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 108112, 2 interactors |
STRINGi | 9606.ENSP00000385905 |
Chemistry databases
BindingDBi | P24855 |
ChEMBLi | CHEMBL3351219 |
PTM databases
GlyConnecti | 2005, 1 N-Linked glycan (1 site) |
GlyGeni | P24855, 2 sites |
iPTMneti | P24855 |
PhosphoSitePlusi | P24855 |
Genetic variation databases
BioMutai | DNASE1 |
DMDMi | 118919 |
Proteomic databases
jPOSTi | P24855 |
MassIVEi | P24855 |
PaxDbi | P24855 |
PeptideAtlasi | P24855 |
PRIDEi | P24855 |
ProteomicsDBi | 5238 54233 [P24855-1] |
Protocols and materials databases
Antibodypediai | 10879, 260 antibodies |
DNASUi | 1773 |
Genome annotation databases
Ensembli | ENST00000246949; ENSP00000246949; ENSG00000213918 [P24855-1] ENST00000407479; ENSP00000385905; ENSG00000213918 [P24855-1] |
GeneIDi | 1773 |
KEGGi | hsa:1773 |
UCSCi | uc002cvr.4, human [P24855-1] |
Organism-specific databases
CTDi | 1773 |
DisGeNETi | 1773 |
GeneCardsi | DNASE1 |
HGNCi | HGNC:2956, DNASE1 |
HPAi | ENSG00000213918, Tissue enhanced (intestine) |
MalaCardsi | DNASE1 |
MIMi | 125505, gene 152700, phenotype |
neXtProti | NX_P24855 |
OpenTargetsi | ENSG00000213918 |
Orphaneti | 300345, Autosomal systemic lupus erythematosus 536, Systemic lupus erythematosus |
PharmGKBi | PA27427 |
VEuPathDBi | HostDB:ENSG00000213918.10 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QQFT, Eukaryota |
GeneTreei | ENSGT00950000182846 |
HOGENOMi | CLU_043335_2_1_1 |
InParanoidi | P24855 |
OMAi | FSCPFTE |
OrthoDBi | 1282784at2759 |
PhylomeDBi | P24855 |
TreeFami | TF329541 |
Enzyme and pathway databases
BRENDAi | 3.1.21.1, 2681 |
PathwayCommonsi | P24855 |
SIGNORi | P24855 |
Miscellaneous databases
BioGRID-ORCSi | 1773, 7 hits in 877 CRISPR screens |
ChiTaRSi | DNASE1, human |
GeneWikii | Deoxyribonuclease_I |
GenomeRNAii | 1773 |
Pharosi | P24855, Tchem |
PROi | PR:P24855 |
RNActi | P24855, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000213918, Expressed in pancreas and 192 other tissues |
ExpressionAtlasi | P24855, baseline and differential |
Genevisiblei | P24855, HS |
Family and domain databases
Gene3Di | 3.60.10.10, 1 hit |
InterProi | View protein in InterPro IPR018057, Deoxyribonuclease-1_AS IPR016202, DNase_I IPR033125, DNASE_I_2 IPR036691, Endo/exonu/phosph_ase_sf IPR005135, Endo/exonuclease/phosphatase |
Pfami | View protein in Pfam PF03372, Exo_endo_phos, 1 hit |
PIRSFi | PIRSF000988, DNase_I_euk, 1 hit |
PRINTSi | PR00130, DNASEI |
SMARTi | View protein in SMART SM00476, DNaseIc, 1 hit |
SUPFAMi | SSF56219, SSF56219, 1 hit |
PROSITEi | View protein in PROSITE PS00919, DNASE_I_1, 1 hit PS00918, DNASE_I_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | DNAS1_HUMAN | |
Accessioni | P24855Primary (citable) accession number: P24855 Secondary accession number(s): B4DV35, Q14UU9, Q14UV0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 1, 1992 |
Last sequence update: | March 1, 1992 | |
Last modified: | February 10, 2021 | |
This is version 207 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Direct protein sequencing, Pharmaceutical, Reference proteomeDocuments
- Human chromosome 16
Human chromosome 16: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families