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O00115 (DNS2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Deoxyribonuclease-2-alpha

EC=3.1.22.1
Alternative name(s):
Acid DNase
Deoxyribonuclease II alpha
Short name=DNase II alpha
Lysosomal DNase II
R31240_2
Gene names
Name:DNASE2
Synonyms:DNASE2A, DNL2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length360 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Hydrolyzes DNA under acidic conditions with a preference for double-stranded DNA. Plays a major role in the degradation of nuclear DNA in cellular apoptosis during development. Necessary for proper fetal development and for definitive erythropoiesis in fetal liver, where it degrades nuclear DNA expelled from erythroid precursor cells.

Catalytic activity

Endonucleolytic cleavage to nucleoside 3'-phosphates and 3'-phosphooligonucleotide end-products.

Subcellular location

Lysosome.

Post-translational modification

Glycosylated. Mutations that eliminate N-glycosylation sites reduce activity, but enzymatic deglycosylation has no effect. Ref.11 Ref.12 Ref.14

Miscellaneous

Not required for the generation of the characteristic DNA fragmentation observed in apoptotic cells, but for the degradation of DNA from dying cells By similarity.

Sequence similarities

Belongs to the DNase II family.

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

RUVBL1Q9Y2651EBI-1051412,EBI-353675
RUVBL2Q9Y2301EBI-1051412,EBI-352939

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 360342Deoxyribonuclease-2-alpha
PRO_0000007291

Sites

Active site2951 Probable

Amino acid modifications

Glycosylation861N-linked (GlcNAc...)
Glycosylation2121N-linked (GlcNAc...) Ref.14 Ref.15
Glycosylation2661N-linked (GlcNAc...)
Glycosylation2901N-linked (GlcNAc...)
Disulfide bond19 ↔ 159 Potential
Disulfide bond267 ↔ 347 Potential
Disulfide bond308 ↔ 327 Potential

Natural variations

Natural variant391R → I.
Corresponds to variant rs36075196 [ dbSNP | Ensembl ].
VAR_048870
Natural variant2041H → R.
Corresponds to variant rs16978744 [ dbSNP | Ensembl ].
VAR_048871
Natural variant3141R → L.
Corresponds to variant rs1061192 [ dbSNP | Ensembl ].
VAR_012044

Experimental info

Mutagenesis191C → A: Loss of activity. Ref.12
Mutagenesis861N → Q: Reduced N-glycosylation, complete loss of N-glycosylation; when associated with Q-212; Q-266 and Q-290. Ref.12
Mutagenesis1511C → A: Loss of activity. Ref.12
Mutagenesis1591C → A: Loss of activity. Ref.12
Mutagenesis2121N → Q: Reduced N-glycosylation, complete loss of N-glycosylation; when associated with Q-86; Q-266 and Q-290. Ref.12
Mutagenesis2661N → Q: Reduced N-glycosylation, complete loss of N-glycosylation; when associated with Q-86; Q-212 and Q-290. Ref.12
Mutagenesis2671C → A: Loss of activity. Ref.12
Mutagenesis2901N → Q: Reduced N-glycosylation, complete loss of N-glycosylation; when associated with Q-86; Q-212 and Q-266. Ref.12
Mutagenesis2951H → A, K, N, R or S: Loss of activity, but not of DNA-binding. Ref.13
Mutagenesis2991C → A: No effect. Ref.12
Mutagenesis3081C → A: Loss of activity. Ref.12
Mutagenesis3271C → A: Loss of activity. Ref.12
Mutagenesis3471C → A: Loss of activity. Ref.12
Sequence conflict160 – 17112Missing in AAB51172. Ref.8

Sequences

Sequence LengthMass (Da)Tools
O00115 [UniParc].

Last modified July 15, 1998. Version 2.
Checksum: DF1BBFBA8A9676EA

FASTA36039,581
        10         20         30         40         50         60 
MIPLLLAALL CVPAGALTCY GDSGQPVDWF VVYKLPALRG SGEAAQRGLQ YKYLDESSGG 

        70         80         90        100        110        120 
WRDGRALINS PEGAVGRSLQ PLYRSNTSQL AFLLYNDQPP QPSKAQDSSM RGHTKGVLLL 

       130        140        150        160        170        180 
DHDGGFWLVH SVPNFPPPAS SAAYSWPHSA CTYGQTLLCV SFPFAQFSKM GKQLTYTYPW 

       190        200        210        220        230        240 
VYNYQLEGIF AQEFPDLENV VKGHHVSQEP WNSSITLTSQ AGAVFQSFAK FSKFGDDLYS 

       250        260        270        280        290        300 
GWLAAALGTN LQVQFWHKTV GILPSNCSDI WQVLNVNQIA FPGPAGPSFN STEDHSKWCV 

       310        320        330        340        350        360 
SPKGPWTCVG DMNRNQGEEQ RGGGTLCAQL PALWKAFQPL VKNYQPCNGM ARKPSRAYKI 

« Hide

References

« Hide 'large scale' references
[1]"Structure and organization of the human deoxyribonuclease II (DNase II) gene."
Yasuda T., Takeshita H., Iida R., Tsutsumi S., Nakajima T., Hosomi O., Nakashima Y., Mori S., Kishi K.
Ann. Hum. Genet. 62:299-305(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Cloning of cDNAs encoding porcine and human DNase II."
Shiokawa D., Tanuma S.
Biochem. Biophys. Res. Commun. 247:864-869(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Molecular cloning and characterization of human and murine DNase II."
Baker K.P., Baron W.F., Henzel W.J., Spencer S.A.
Gene 215:281-289(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"The cloning and expression of human deoxyribonuclease II. A possible role in apoptosis."
Krieser R.J., Eastman A.
J. Biol. Chem. 273:30909-30914(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]"Molecular cloning of the cDNA encoding human deoxyribonuclease II."
Yasuda T., Takeshita H., Iida R., Nakajima T., Hosomi O., Nakashima Y., Kishi K.
J. Biol. Chem. 273:2610-2616(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]Mural R.J., Istrail S., Sutton G.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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]"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: Muscle.
[11]"Revised structure of the active form of human deoxyribonuclease IIalpha."
MacLea K.S., Krieser R.J., Eastman A.
Biochem. Biophys. Res. Commun. 292:415-421(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: LACK OF PROTEOLYTIC PROCESSING, GLYCOSYLATION.
[12]"Structural requirements of human DNase II alpha for formation of the active enzyme: the role of the signal peptide, N-glycosylation, and disulphide bridging."
MacLea K.S., Krieser R.J., Eastman A.
Biochem. J. 371:867-876(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF CYS-19; ASN-86; CYS-151; CYS-159; ASN-212; ASN-266; CYS-267; ASN-290; CYS-299; CYS-308; CYS-327 AND CYS-347, GLYCOSYLATION, DISULFIDE BONDS.
[13]"A family history of deoxyribonuclease II: surprises from Trichinella spiralis and Burkholderia pseudomallei."
MacLea K.S., Krieser R.J., Eastman A.
Gene 305:1-12(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF HIS-295.
[14]"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry."
Zhang H., Li X.-J., Martin D.B., Aebersold R.
Nat. Biotechnol. 21:660-666(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-212.
[15]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-212.
Tissue: Liver.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB008564 Genomic DNA. Translation: BAB55598.1.
AF060222 mRNA. Translation: AAC39852.1.
AF045937 mRNA. Translation: AAC35751.1.
AF047016 mRNA. Translation: AAC77366.1.
AB004574 mRNA. Translation: BAA28623.1.
BT007047 mRNA. Translation: AAP35696.1.
AK315358 mRNA. Translation: BAG37753.1.
AD000092 Genomic DNA. Translation: AAB51172.1.
CH471106 Genomic DNA. Translation: EAW84320.1.
BC010419 mRNA. Translation: AAH10419.3.
BC065209 mRNA. Translation: AAH65209.1.
CCDSCCDS12284.1.
PIRJE0206.
T45071.
RefSeqNP_001366.1. NM_001375.2.
UniGeneHs.118243.

3D structure databases

ProteinModelPortalO00115.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108116. 8 interactions.
IntActO00115. 1 interaction.
MINTMINT-2997367.
STRING9606.ENSP00000222219.

Chemistry

BindingDBO00115.
ChEMBLCHEMBL1250342.

PTM databases

PhosphoSiteO00115.

Proteomic databases

MaxQBO00115.
PaxDbO00115.
PeptideAtlasO00115.
PRIDEO00115.

Protocols and materials databases

DNASU1777.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000222219; ENSP00000222219; ENSG00000105612.
GeneID1777.
KEGGhsa:1777.
UCSCuc002mvn.1. human.

Organism-specific databases

CTD1777.
GeneCardsGC19M012986.
HGNCHGNC:2960. DNASE2.
MIM126350. gene.
neXtProtNX_O00115.
PharmGKBPA27431.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG145330.
HOGENOMHOG000261682.
HOVERGENHBG051387.
InParanoidO00115.
KOK01158.
OMANLQVQFW.
PhylomeDBO00115.
TreeFamTF314536.

Enzyme and pathway databases

BRENDA3.1.22.1. 2681.
ReactomeREACT_11123. Membrane Trafficking.

Gene expression databases

ArrayExpressO00115.
BgeeO00115.
CleanExHS_DNASE2.
GenevestigatorO00115.

Family and domain databases

InterProIPR004947. DNase_II.
[Graphical view]
PANTHERPTHR10858. PTHR10858. 1 hit.
PfamPF03265. DNase_II. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi1777.
NextBio7235.
PROO00115.
SOURCESearch...

Entry information

Entry nameDNS2A_HUMAN
AccessionPrimary (citable) accession number: O00115
Secondary accession number(s): B2RD06, O43910
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 15, 1998
Last modified: July 9, 2014
This is version 125 of the entry and version 2 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

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 19

Human chromosome 19: entries, gene names and cross-references to MIM