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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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	Defects in DNASE1 are a cause of susceptibility to systemic lupus erythematosus (SLE) [MIM:152700]. A chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system. Ref.8
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	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
Cellular component	extracellular region Traceable author statement. Source: ProtInc nuclear envelope Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	actin binding Inferred from electronic annotation. Source: UniProtKB-KW deoxyribonuclease I activity Inferred from electronic annotation. Source: 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.6 Ref.7
	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.		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.		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

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: 2251263] [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: 7762978] [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: 11241278] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"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: 15616553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.
[6]	"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: 3263467] [Abstract] Cited for: PROTEIN SEQUENCE OF 23-45 AND 73-95. Tissue: Urine.
[7]	"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: 2277032] [Abstract] Cited for: PROTEIN SEQUENCE OF 23-49. Tissue: Urine.
[8]	"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: 11479590] [Abstract] Cited for: INVOLVEMENT IN SLE.
[9]	"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: 7625762] [Abstract] Cited for: VARIANT DNASE1*3.
[10]	"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: 7867802] [Abstract] Cited for: VARIANT DNASE1*4.
[11]	"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: 9420147] [Abstract] Cited for: VARIANT DNASE1*5.
[12]	"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: 10381379] [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. AC005203 Genomic DNA. Translation: AAC24721.1. BC029437 mRNA. Translation: AAH29437.1.
IPI	IPI00031065.
PIR	NDHU1. A38417.
RefSeq	NP_005214.2. NM_005223.3.
UniGene	Hs.629638.
3D structure databases
ProteinModelPortal	P24855.
SMR	P24855. Positions 23-281.
ModBase	Search...
Protein-protein interaction databases
STRING	P24855.
PTM databases
PhosphoSite	P24855.
Polymorphism databases
DMDM	118919.
Proteomic databases
PRIDE	P24855.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000246949; ENSP00000246949; ENSG00000213918. ENST00000407479; ENSP00000385905; ENSG00000213918.
GeneID	1773.
KEGG	hsa:1773.
UCSC	uc002cvr.1. human.
Organism-specific databases
CTD	1773.
GeneCards	GC16P003630.
H-InvDB	HIX0012773.
HGNC	HGNC:2956. DNASE1.
HPA	HPA010703.
MIM	125505. gene. 152700. phenotype.
neXtProt	NX_P24855.
PharmGKB	PA27427.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG07423.
HOGENOM	HBG717602.
HOVERGEN	HBG051368.
InParanoid	P24855.
OMA	SYKERYL.
OrthoDB	EOG4ZS93V.
PhylomeDB	P24855.
Enzyme and pathway databases
BRENDA	3.1.21.1. 2681.
Gene expression databases
ArrayExpress	P24855.
Bgee	P24855.
CleanEx	HS_DNASE1.
Genevestigator	P24855.
GermOnline	ENSG00000126594. Homo sapiens.
Family and domain databases
InterPro	IPR018057. Deoxyribonuclease-1_AS. IPR016202. DNase_I-like. IPR008185. DNase_I_euk. IPR005135. Endo/exonuclease/phosphatase. [Graphical view]
KO	K11994.
PANTHER	PTHR11371. DNase_I. 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. Exo_endo_phos. 1 hit.
PROSITE	PS00919. DNASE_I_1. 1 hit. PS00918. DNASE_I_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00003. Dornase Alfa.
NextBio	7213.
SOURCE	Search...

Entry information

Entry name

DNAS1_HUMAN

Accession

Primary (citable) accession number: P24855

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	March 1, 1992
Last modified:	December 14, 2011
This is version 127 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.