P24855 (DNAS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	282 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Apoptosis
Cellular component	Nucleus Secreted
Coding sequence diversity	Polymorphism
Disease	Systemic lupus erythematosus
Domain	Signal
Ligand	Actin-binding Calcium
Molecular function	Endonuclease Hydrolase Nuclease
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Pharmaceutical Reference proteome
Gene Ontology (GO)
Biological_process	DNA catabolic process Inferred from electronic annotation. Source: InterPro apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW nucleic acid phosphodiester bond hydrolysis Inferred from electronic annotation. Source: GOC
Cellular_component	extracellular region Traceable author statement PubMed 2349940. Source: ProtInc nuclear envelope Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	deoxyribonuclease I activity Inferred from electronic annotation. Source: UniProtKB-EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Ref.8 Ref.9

Chain

23 – 282

260

Deoxyribonuclease-1

PRO_0000007277

Sites

Active site

100

1

By similarity

Active site

156

1

By similarity

Amino acid modifications

Glycosylation

40

1

N-linked (GlcNAc...)

Glycosylation

128

1

N-linked (GlcNAc...) Potential

Disulfide bond

123 ↔ 126

By similarity

Disulfide bond

195 ↔ 231

Essential for enzymatic activity By similarity

Natural variations

Natural variant

2

1

R → S.
Corresponds to variant rs8176927 [ dbSNP | Ensembl ].

VAR_024434

Natural variant

31

1

Q → E in allele DNASE1*4.
Corresponds to variant rs77254040 [ dbSNP | Ensembl ].

VAR_002264

Natural variant

107

1

R → G.
Corresponds to variant rs8176928 [ dbSNP | Ensembl ].

VAR_029172

Natural variant

114

1

V → M in allele DNASE1*5.

VAR_009300

Natural variant

127

1

G → R.
Corresponds to variant rs8176919 [ dbSNP | Ensembl ].

VAR_024435

Natural variant

154

1

P → A in allele DNASE1*3.
Corresponds to variant rs1799891 [ dbSNP | Ensembl ].

VAR_002265

Natural variant

207

1

R → C in allele DNASE1*6.
Corresponds to variant rs148373909 [ dbSNP | Ensembl ].

VAR_009301

Natural variant

231

1

C → Y.
Corresponds to variant rs8176940 [ dbSNP | Ensembl ].

VAR_029173

Natural variant

244

1

R → Q in allele DNASE1*1. Ref.2
Corresponds to variant rs1053874 [ dbSNP | Ensembl ].

VAR_002266

Natural variant

246

1

A → P.
Corresponds to variant rs8176939 [ dbSNP | Ensembl ].

VAR_029174

Natural variant

262

1

G → D.
Corresponds to variant rs8176924 [ dbSNP | Ensembl ].

VAR_029175

Experimental info

Sequence conflict

143

1

R → Q in BAE96964. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

282

Helix Strand Turn

Details...

Beta strand

24 – 34

11

Helix

35 – 38

4

Helix

41 – 51

11

Beta strand

55 – 62

8

Helix

68 – 77

10

Turn

78 – 80

3

Beta strand

86 – 89

4

Beta strand

93 – 98

6

Beta strand

100 – 106

7

Turn

108 – 110

3

Beta strand

112 – 118

7

Turn

124 – 127

4

Beta strand

136 – 141

6

Beta strand

149 – 154

6

Helix

159 – 161

3

Helix

162 – 180

19

Beta strand

185 – 190

6

Turn

195 – 197

3

Helix

200 – 205

6

Helix

207 – 210

4

Beta strand

214 – 216

3

Beta strand

225 – 228

4

Beta strand

234 – 240

7

Helix

241 – 246

6

Helix

257 – 260

4

Helix

265 – 271

7

Beta strand

277 – 281

5

Sequences

	Sequence		Length	Mass (Da)
	P24855 [UniParc]. Last modified March 1, 1992. Version 1. Checksum: 040042E2D23555B6	FASTA	282	31,434
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

IPI

IPI00031065.

PIR

NDHU1. A38417.

RefSeq

NP_005214.2. NM_005223.3.
XP_005255203.1. XM_005255146.1.
XP_005255204.1. XM_005255147.1.

UniGene

Hs.629638.
Hs.733045.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4AWN	X-ray	1.95	A	23-282	[»]

ProteinModelPortal

P24855.

SMR

P24855. Positions 23-282.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-4722539.

STRING

9606.ENSP00000246949.

PTM databases

PhosphoSite

P24855.

Polymorphism databases

DMDM

118919.

Proteomic databases

PaxDb

P24855.

PRIDE

P24855.

Protocols and materials databases

DNASU

1773.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000246949; ENSP00000246949; ENSG00000213918.
ENST00000407479; ENSP00000385905; ENSG00000213918.

GeneID

1773.

KEGG

hsa:1773.

UCSC

uc002cvr.3. human.

Organism-specific databases

CTD

1773.

GeneCards

GC16P003663.

HGNC

HGNC:2956. DNASE1.

HPA

HPA010703.

MIM

125505. gene.
152700. phenotype.

neXtProt

NX_P24855.

Orphanet

536. Systemic lupus erythematosus.

PharmGKB

PA27427.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG46375.

HOGENOM

HOG000059570.

HOVERGEN

HBG051368.

InParanoid

P24855.

KO

K11994.

OMA

TKMSNAT.

PhylomeDB

P24855.

Enzyme and pathway databases

BRENDA

3.1.21.1. 2681.

Gene expression databases

ArrayExpress

P24855.

Bgee

P24855.

CleanEx

HS_DNASE1.

Genevestigator

P24855.

Family and domain databases

Gene3D

3.60.10.10. 1 hit.

InterPro

IPR018057. Deoxyribonuclease-1_AS.
IPR016202. DNase_I.
IPR005135. Endo/exonuclease/phosphatase.
[Graphical view]

PANTHER

PTHR11371. PTHR11371. 1 hit.

Pfam

PF03372. Exo_endo_phos. 1 hit.
[Graphical view]

PIRSF

PIRSF000988. DNase_I_euk. 1 hit.

PRINTS

PR00130. DNASEI.

SMART

SM00476. DNaseIc. 1 hit.
[Graphical view]

SUPFAM

SSF56219. SSF56219. 1 hit.

PROSITE

PS00919. DNASE_I_1. 1 hit.
PS00918. DNASE_I_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

DNASE1. human.

DrugBank

DB00003. Dornase Alfa.

GeneWiki

Deoxyribonuclease_I.

GenomeRNAi

1773.

NextBio

7213.

PRO

P24855.

SOURCE

Search...

Entry information

Entry name

DNAS1_HUMAN

Accession

Primary (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:	November 13, 2013
This is version 146 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.