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P24855 (DNAS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 150. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Deoxyribonuclease-1

EC=3.1.21.1
Alternative name(s):
Deoxyribonuclease I
Short name=DNase I
INN=Dornase alfa
Gene names
Name:DNASE1
Synonyms:DNL1, DRNI
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length282 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Among other functions, seems to be involved in cell death by apoptosis. Binds specifically to G-actin and blocks actin polymerization By similarity.

Catalytic activity

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

Cofactor

Divalent cations. Prefers calcium or magnesium.

Subcellular location

Secreted. Nucleus envelope. Note: Secretory protein, stored in zymogen granules and found in the nuclear envelope.

Tissue specificity

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

Polymorphism

At least 6 alleles of DNASE1 are known: DNASE1*1 to DNASE1*6. The sequence shown is that of DNASE1*2.

Involvement in disease

Systemic lupus erythematosus (SLE) [MIM:152700]: 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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.10

Pharmaceutical use

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.

Sequence similarities

Belongs to the DNase I family.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentNucleus
Secreted
   Coding sequence diversityPolymorphism
   DiseaseSystemic lupus erythematosus
   DomainSignal
   LigandActin-binding
Calcium
   Molecular functionEndonuclease
Hydrolase
Nuclease
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Pharmaceutical
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentextracellular region

Traceable author statement PubMed 2349940. Source: ProtInc

nuclear envelope

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functiondeoxyribonuclease I activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Ref.8 Ref.9
Chain23 – 282260Deoxyribonuclease-1
PRO_0000007277

Sites

Active site1001 By similarity
Active site1561 By similarity

Amino acid modifications

Glycosylation401N-linked (GlcNAc...)
Glycosylation1281N-linked (GlcNAc...) Potential
Disulfide bond123 ↔ 126 By similarity
Disulfide bond195 ↔ 231Essential for enzymatic activity By similarity

Natural variations

Natural variant21R → S.
Corresponds to variant rs8176927 [ dbSNP | Ensembl ].
VAR_024434
Natural variant311Q → E in allele DNASE1*4.
Corresponds to variant rs77254040 [ dbSNP | Ensembl ].
VAR_002264
Natural variant1071R → G.
Corresponds to variant rs8176928 [ dbSNP | Ensembl ].
VAR_029172
Natural variant1141V → M in allele DNASE1*5.
VAR_009300
Natural variant1271G → R.
Corresponds to variant rs8176919 [ dbSNP | Ensembl ].
VAR_024435
Natural variant1541P → A in allele DNASE1*3.
Corresponds to variant rs1799891 [ dbSNP | Ensembl ].
VAR_002265
Natural variant2071R → C in allele DNASE1*6.
Corresponds to variant rs148373909 [ dbSNP | Ensembl ].
VAR_009301
Natural variant2311C → Y.
Corresponds to variant rs8176940 [ dbSNP | Ensembl ].
VAR_029173
Natural variant2441R → Q in allele DNASE1*1. Ref.2
Corresponds to variant rs1053874 [ dbSNP | Ensembl ].
VAR_002266
Natural variant2461A → P.
Corresponds to variant rs8176939 [ dbSNP | Ensembl ].
VAR_029174
Natural variant2621G → D.
Corresponds to variant rs8176924 [ dbSNP | Ensembl ].
VAR_029175

Experimental info

Sequence conflict1431R → Q in BAE96964. Ref.4

Secondary structure

................................................... 282
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P24855 [UniParc].

Last modified March 1, 1992. Version 1.
Checksum: 040042E2D23555B6

FASTA28231,434
        10         20         30         40         50         60 
MRGMKLLGAL LALAALLQGA VSLKIAAFNI QTFGETKMSN ATLVSYIVQI LSRYDIALVQ 

        70         80         90        100        110        120 
EVRDSHLTAV GKLLDNLNQD APDTYHYVVS EPLGRNSYKE RYLFVYRPDQ VSAVDSYYYD 

       130        140        150        160        170        180 
DGCEPCGNDT FNREPAIVRF FSRFTEVREF AIVPLHAAPG DAVAEIDALY DVYLDVQEKW 

       190        200        210        220        230        240 
GLEDVMLMGD FNAGCSYVRP SQWSSIRLWT SPTFQWLIPD SADTTATPTH CAYDRIVVAG 

       250        260        270        280 
MLLRGAVVPD SALPFNFQAA YGLSDQLAQA ISDHYPVEVM LK 

« Hide

References

« Hide 'large scale' references
[1]"Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum."
Shak S., Capon D.J., Hellmiss R., Marsters S.A., Baker C.L.
Proc. Natl. Acad. Sci. U.S.A. 87:9188-9192(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Structure of the human deoxyribonuclease I (DNase I) gene: identification of the nucleotide substitution that generates its classical genetic polymorphism."
Yasuda T., Kishi K., Yanagawa Y., Yoshida A.
Ann. Hum. Genet. 59:1-15(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLN-244.
Tissue: Placenta.
[3]"DNase I mediates internucleosomal DNA degradation in human cells undergoing drug-induced apoptosis."
Oliveri M., Daga A., Cantoni C., Lunardi C., Millo R., Puccetti A.
Eur. J. Immunol. 31:743-751(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Characterization of human deoxyribonuclease I gene (DNASE1) promoters reveals the utilization of two transcription-starting exons and the involvement of Sp1 in its transcriptional regulation."
Kominato Y., Ueki M., Iida R., Kawai Y., Nakajima T., Makita C., Itoi M., Tajima Y., Kishi K., Yasuda T.
FEBS J. 273:3094-3105(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Pancreas.
[5]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Kidney.
[8]"A human urine-derived interleukin 1 inhibitor. Homology with deoxyribonuclease I."
Rosenstreich D.L., Tu J.H., Kinkade P.R., Maurer-Fogy I., Kahn J., Barton R.W., Farina P.R.
J. Exp. Med. 168:1767-1779(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 23-45 AND 73-95.
Tissue: Urine.
[9]"Human genetically polymorphic deoxyribonuclease: purification, characterization, and multiplicity of urine deoxyribonuclease I."
Yasuda T., Awazu S., Sato W., Iida R., Tanaka Y., Kishi K.
J. Biochem. 108:393-398(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 23-49.
Tissue: Urine.
[10]"Mutation of DNASE1 in people with systemic lupus erythematosus."
Yasutomo K., Horiuchi T., Kagami S., Tsukamoto H., Hashimura C., Urushihara M., Kuroda Y.
Nat. Genet. 28:313-314(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SLE.
[11]"Molecular analysis of the third allele of human deoxyribonuclease I polymorphism."
Yasuda T., Nadano D., Takeshita H., Tenjo E., Kishi K.
Ann. Hum. Genet. 59:139-147(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DNASE1*3.
[12]"The molecular basis for genetic polymorphism of human deoxyribonuclease I: identification of the nucleotide substitution that generates the fourth allele."
Yasuda T., Nadano D., Takeshita H., Tenjo E., Sawazaki K., Ootani M., Kishi K.
FEBS Lett. 359:211-214(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DNASE1*4.
[13]"The fifth allele of the human deoxyribonuclease I (DNase I) polymorphism."
Iida R., Yasuda T., Aoyama M., Tsubota E., Kobayashi M., Yuasa I., Matsuki T., Kishi K.
Electrophoresis 18:1936-1939(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DNASE1*5.
[14]"A new allele, DNASE1*6, of human deoxyribonuclease I polymorphism encodes an Arg to Cys substitution responsible for its instability."
Yasuda T., Takeshita H., Iida R., Kogure S., Kishi K.
Biochem. Biophys. Res. Commun. 260:280-283(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DNASE1*6.
+Additional computationally mapped references.

Web resources

Pulmozyme

Clinical information on Pulmozyme

Wikipedia

Deoxyribonuclease entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
AC005203 Genomic DNA. Translation: AAC24721.1.
CH471112 Genomic DNA. Translation: EAW85344.1.
BC029437 mRNA. Translation: AAH29437.1.
PIRNDHU1. A38417.
RefSeqNP_005214.2. NM_005223.3.
UniGeneHs.629638.
Hs.733045.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4AWNX-ray1.95A23-282[»]
ProteinModelPortalP24855.
SMRP24855. Positions 23-282.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108112. 1 interaction.
MINTMINT-4722539.
STRING9606.ENSP00000246949.

Chemistry

DrugBankDB00003. Dornase Alfa.

PTM databases

PhosphoSiteP24855.

Polymorphism databases

DMDM118919.

Proteomic databases

PaxDbP24855.
PRIDEP24855.

Protocols and materials databases

DNASU1773.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000246949; ENSP00000246949; ENSG00000213918.
ENST00000407479; ENSP00000385905; ENSG00000213918.
GeneID1773.
KEGGhsa:1773.
UCSCuc002cvr.3. human.

Organism-specific databases

CTD1773.
GeneCardsGC16P003663.
HGNCHGNC:2956. DNASE1.
HPAHPA010703.
MIM125505. gene.
152700. phenotype.
neXtProtNX_P24855.
Orphanet536. Systemic lupus erythematosus.
PharmGKBPA27427.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46375.
HOGENOMHOG000059570.
HOVERGENHBG051368.
InParanoidP24855.
KOK11994.
OMATKMSNAT.
PhylomeDBP24855.
TreeFamTF329541.

Enzyme and pathway databases

BRENDA3.1.21.1. 2681.

Gene expression databases

ArrayExpressP24855.
BgeeP24855.
CleanExHS_DNASE1.
GenevestigatorP24855.

Family and domain databases

Gene3D3.60.10.10. 1 hit.
InterProIPR018057. Deoxyribonuclease-1_AS.
IPR016202. DNase_I.
IPR005135. Endo/exonuclease/phosphatase.
[Graphical view]
PANTHERPTHR11371. PTHR11371. 1 hit.
PfamPF03372. Exo_endo_phos. 1 hit.
[Graphical view]
PIRSFPIRSF000988. DNase_I_euk. 1 hit.
PRINTSPR00130. DNASEI.
SMARTSM00476. DNaseIc. 1 hit.
[Graphical view]
SUPFAMSSF56219. SSF56219. 1 hit.
PROSITEPS00919. DNASE_I_1. 1 hit.
PS00918. DNASE_I_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSDNASE1. human.
GeneWikiDeoxyribonuclease_I.
GenomeRNAi1773.
NextBio7213.
PROP24855.
SOURCESearch...

Entry information

Entry nameDNAS1_HUMAN
AccessionPrimary (citable) accession number: P24855
Secondary accession number(s): Q14UU9, Q14UV0
Entry history
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: March 1, 1992
Last modified: April 16, 2014
This is version 150 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM