O00115 (DNS2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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 › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	360 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	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

Keywords
Biological process	Apoptosis
Cellular component	Lysosome
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Developmental protein Endonuclease Hydrolase Nuclease
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA catabolic process Inferred from electronic annotation. Source: Compara DNA metabolic process Traceable author statement Ref.3. Source: ProtInc apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW erythrocyte differentiation Inferred from electronic annotation. Source: Compara
Cellular_component	lysosome Traceable author statement Ref.3. Source: ProtInc
Molecular_function	DNA binding Traceable author statement Ref.3. Source: ProtInc deoxyribonuclease II activity Traceable author statement Ref.3. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RUVBL1	Q9Y265	1	EBI-1051412,EBI-353675
RUVBL2	Q9Y230	1	EBI-1051412,EBI-352939

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Chain	19 – 360	342	Deoxyribonuclease-2-alpha		PRO_0000007291
Sites
	Active site	295	1	Probable
Amino acid modifications
	Glycosylation	86	1	N-linked (GlcNAc...)
	Glycosylation	212	1	N-linked (GlcNAc...) Ref.14 Ref.15
	Glycosylation	266	1	N-linked (GlcNAc...)
	Glycosylation	290	1	N-linked (GlcNAc...)
	Disulfide bond	19 ↔ 159		Potential
	Disulfide bond	267 ↔ 347		Potential
	Disulfide bond	308 ↔ 327		Potential
Natural variations
	Natural variant	39	1	R → I. Corresponds to variant rs36075196 [ dbSNP | Ensembl ].		VAR_048870
	Natural variant	204	1	H → R. Corresponds to variant rs16978744 [ dbSNP | Ensembl ].		VAR_048871
	Natural variant	314	1	R → L. Corresponds to variant rs1061192 [ dbSNP | Ensembl ].		VAR_012044
Experimental info
	Mutagenesis	19	1	C → A: Loss of activity. Ref.12
	Mutagenesis	86	1	N → Q: Reduced N-glycosylation, complete loss of N-glycosylation; when associated with Q-212; Q-266 and Q-290. Ref.12
	Mutagenesis	151	1	C → A: Loss of activity. Ref.12
	Mutagenesis	159	1	C → A: Loss of activity. Ref.12
	Mutagenesis	212	1	N → Q: Reduced N-glycosylation, complete loss of N-glycosylation; when associated with Q-86; Q-266 and Q-290. Ref.12
	Mutagenesis	266	1	N → Q: Reduced N-glycosylation, complete loss of N-glycosylation; when associated with Q-86; Q-212 and Q-290. Ref.12
	Mutagenesis	267	1	C → A: Loss of activity. Ref.12
	Mutagenesis	290	1	N → Q: Reduced N-glycosylation, complete loss of N-glycosylation; when associated with Q-86; Q-212 and Q-266. Ref.12
	Mutagenesis	295	1	H → A, K, N, R or S: Loss of activity, but not of DNA-binding. Ref.13
	Mutagenesis	299	1	C → A: No effect. Ref.12
	Mutagenesis	308	1	C → A: Loss of activity. Ref.12
	Mutagenesis	327	1	C → A: Loss of activity. Ref.12
	Mutagenesis	347	1	C → A: Loss of activity. Ref.12
	Sequence conflict	160 – 171	12	Missing in AAB51172. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	O00115 [UniParc]. Last modified July 15, 1998. Version 2. Checksum: DF1BBFBA8A9676EA	FASTA	360	39,581
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, MASS SPECTROMETRY. 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.
IPI	IPI00010348.
PIR	JE0206. T45071.
RefSeq	NP_001366.1. NM_001375.2.
UniGene	Hs.118243.
3D structure databases
ProteinModelPortal	O00115.
ModBase	Search...
Protein-protein interaction databases
IntAct	O00115. 1 interaction.
STRING	9606.ENSP00000222219.
PTM databases
PhosphoSite	O00115.
Proteomic databases
PaxDb	O00115.
PeptideAtlas	O00115.
PRIDE	O00115.
Protocols and materials databases
DNASU	1777.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000222219; ENSP00000222219; ENSG00000105612.
GeneID	1777.
KEGG	hsa:1777.
UCSC	uc002mvn.1. human.
Organism-specific databases
CTD	1777.
GeneCards	GC19M012986.
HGNC	HGNC:2960. DNASE2.
MIM	126350. gene.
neXtProt	NX_O00115.
PharmGKB	PA27431.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG145330.
HOGENOM	HOG000261682.
HOVERGEN	HBG051387.
InParanoid	O00115.
KO	K01158.
OMA	NLQVQFW.
OrthoDB	EOG49W2FX.
PhylomeDB	O00115.
Enzyme and pathway databases
BRENDA	3.1.22.1. 2681.
Reactome	REACT_11123. Membrane Trafficking.
Gene expression databases
ArrayExpress	O00115.
Bgee	O00115.
CleanEx	HS_DNASE2.
Genevestigator	O00115.
GermOnline	ENSG00000105612. Homo sapiens.
Family and domain databases
InterPro	IPR004947. DNase_II. [Graphical view]
PANTHER	PTHR10858. PTHR10858. 1 hit.
Pfam	PF03265. DNase_II. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O00115.
ChEMBL	CHEMBL1250342.
GenomeRNAi	1777.
NextBio	7235.
SOURCE	Search...

Entry information

Entry name

DNS2A_HUMAN

Accession

Primary (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:	April 3, 2013
This is version 114 of the entry and version 2 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.