UniProtKB - P24855 (DNAS1_HUMAN)
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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
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 I activity Source: UniProtKB-EC
GO - Biological processi
- apoptotic process Source: UniProtKB-KW
- 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. |
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
EuPathDBi | HostDB:ENSG00000213918.10. |
HGNCi | HGNC:2956. DNASE1. |
MIMi | 125505. gene. |
neXtProti | NX_P24855. |
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:152700Pharmaceutical 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 | 536. Systemic lupus erythematosus. |
PharmGKBi | PA27427. |
Chemistry databases
ChEMBLi | CHEMBL3351219. |
Polymorphism and mutation 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
PaxDbi | P24855. |
PeptideAtlasi | P24855. |
PRIDEi | P24855. |
PTM databases
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. |
CleanExi | HS_DNASE1. |
ExpressionAtlasi | P24855. baseline and differential. |
Genevisiblei | P24855. HS. |
Organism-specific databases
HPAi | HPA010703. |
Interactioni
GO - Molecular functioni
- actin binding Source: UniProtKB-KW
Protein-protein interaction databases
BioGridi | 108112. 2 interactors. |
STRINGi | 9606.ENSP00000246949. |
Chemistry databases
BindingDBi | P24855. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Beta strandi | 24 – 34 | Combined sources | 11 | |
Helixi | 35 – 38 | Combined sources | 4 | |
Helixi | 41 – 51 | Combined sources | 11 | |
Beta strandi | 55 – 62 | Combined sources | 8 | |
Helixi | 68 – 77 | Combined sources | 10 | |
Turni | 78 – 80 | Combined sources | 3 | |
Beta strandi | 86 – 89 | Combined sources | 4 | |
Beta strandi | 93 – 98 | Combined sources | 6 | |
Beta strandi | 100 – 106 | Combined sources | 7 | |
Turni | 108 – 110 | Combined sources | 3 | |
Beta strandi | 112 – 118 | Combined sources | 7 | |
Turni | 124 – 127 | Combined sources | 4 | |
Beta strandi | 136 – 141 | Combined sources | 6 | |
Beta strandi | 149 – 154 | Combined sources | 6 | |
Helixi | 159 – 161 | Combined sources | 3 | |
Helixi | 162 – 180 | Combined sources | 19 | |
Beta strandi | 185 – 190 | Combined sources | 6 | |
Turni | 195 – 197 | Combined sources | 3 | |
Helixi | 200 – 205 | Combined sources | 6 | |
Helixi | 207 – 210 | Combined sources | 4 | |
Beta strandi | 214 – 216 | Combined sources | 3 | |
Beta strandi | 225 – 228 | Combined sources | 4 | |
Beta strandi | 234 – 240 | Combined sources | 7 | |
Helixi | 241 – 246 | Combined sources | 6 | |
Helixi | 257 – 260 | Combined sources | 4 | |
Helixi | 265 – 271 | Combined sources | 7 | |
Beta strandi | 277 – 281 | Combined sources | 5 |
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 | [»] | |
ProteinModelPortali | P24855. | |||||
SMRi | P24855. | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Family & Domainsi
Sequence similaritiesi
Belongs to the DNase I family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG410IFZB. Eukaryota. ENOG410Z4MV. LUCA. |
GeneTreei | ENSGT00390000013146. |
HOGENOMi | HOG000059570. |
HOVERGENi | HBG051368. |
InParanoidi | P24855. |
KOi | K11994. |
OMAi | RYLFVFR. |
OrthoDBi | EOG091G0I0B. |
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 basket
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.
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
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 »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:rs148373909Ensembl. | 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:rs1053874Ensembl. | 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. [P24855-1] 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] |
UniGenei | Hs.629638. Hs.733045. |
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 splicing, PolymorphismSimilar proteinsi
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: | March 28, 2018 | |
This is version 186 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. |