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O00115

- DNS2A_HUMAN

UniProt

O00115 - DNS2A_HUMAN

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Protein

Deoxyribonuclease-2-alpha

Gene
DNASE2, DNASE2A, DNL2
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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 activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei295 – 2951 Inferred

GO - Molecular functioni

  1. deoxyribonuclease II activity Source: RefGenome
  2. DNA binding Source: ProtInc

GO - Biological processi

  1. apoptotic DNA fragmentation Source: RefGenome
  2. DNA metabolic process Source: ProtInc
  3. erythrocyte differentiation Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Endonuclease, Hydrolase, Nuclease

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

BRENDAi3.1.22.1. 2681.
ReactomeiREACT_19287. Lysosome Vesicle Biogenesis.

Names & Taxonomyi

Protein namesi
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 namesi
Name:DNASE2
Synonyms:DNASE2A, DNL2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 19

Organism-specific databases

HGNCiHGNC:2960. DNASE2.

Subcellular locationi

GO - Cellular componenti

  1. extracellular vesicular exosome Source: UniProt
  2. intracellular Source: RefGenome
  3. lysosome Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Lysosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi19 – 191C → A: Loss of activity. 1 Publication
Mutagenesisi86 – 861N → Q: Reduced N-glycosylation, complete loss of N-glycosylation; when associated with Q-212; Q-266 and Q-290. 1 Publication
Mutagenesisi151 – 1511C → A: Loss of activity. 1 Publication
Mutagenesisi159 – 1591C → A: Loss of activity. 1 Publication
Mutagenesisi212 – 2121N → Q: Reduced N-glycosylation, complete loss of N-glycosylation; when associated with Q-86; Q-266 and Q-290. 1 Publication
Mutagenesisi266 – 2661N → Q: Reduced N-glycosylation, complete loss of N-glycosylation; when associated with Q-86; Q-212 and Q-290. 1 Publication
Mutagenesisi267 – 2671C → A: Loss of activity. 1 Publication
Mutagenesisi290 – 2901N → Q: Reduced N-glycosylation, complete loss of N-glycosylation; when associated with Q-86; Q-212 and Q-266. 1 Publication
Mutagenesisi295 – 2951H → A, K, N, R or S: Loss of activity, but not of DNA-binding. 1 Publication
Mutagenesisi299 – 2991C → A: No effect. 1 Publication
Mutagenesisi308 – 3081C → A: Loss of activity. 1 Publication
Mutagenesisi327 – 3271C → A: Loss of activity. 1 Publication
Mutagenesisi347 – 3471C → A: Loss of activity. 1 Publication

Organism-specific databases

PharmGKBiPA27431.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818 Reviewed predictionAdd
BLAST
Chaini19 – 360342Deoxyribonuclease-2-alphaPRO_0000007291Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi19 ↔ 159 Reviewed prediction
Glycosylationi86 – 861N-linked (GlcNAc...)
Glycosylationi212 – 2121N-linked (GlcNAc...)2 Publications
Glycosylationi266 – 2661N-linked (GlcNAc...)
Disulfide bondi267 ↔ 347 Reviewed prediction
Glycosylationi290 – 2901N-linked (GlcNAc...)
Disulfide bondi308 ↔ 327 Reviewed prediction

Post-translational modificationi

Glycosylated. Mutations that eliminate N-glycosylation sites reduce activity, but enzymatic deglycosylation has no effect.3 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiO00115.
PaxDbiO00115.
PeptideAtlasiO00115.
PRIDEiO00115.

PTM databases

PhosphoSiteiO00115.

Expressioni

Gene expression databases

ArrayExpressiO00115.
BgeeiO00115.
CleanExiHS_DNASE2.
GenevestigatoriO00115.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
RUVBL1Q9Y2651EBI-1051412,EBI-353675
RUVBL2Q9Y2301EBI-1051412,EBI-352939

Protein-protein interaction databases

BioGridi108116. 8 interactions.
IntActiO00115. 1 interaction.
MINTiMINT-2997367.
STRINGi9606.ENSP00000222219.

Structurei

3D structure databases

ProteinModelPortaliO00115.

Family & Domainsi

Sequence similaritiesi

Belongs to the DNase II family.

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG145330.
HOGENOMiHOG000261682.
HOVERGENiHBG051387.
InParanoidiO00115.
KOiK01158.
OMAiNLQVQFW.
PhylomeDBiO00115.
TreeFamiTF314536.

Family and domain databases

InterProiIPR004947. DNase_II.
[Graphical view]
PANTHERiPTHR10858. PTHR10858. 1 hit.
PfamiPF03265. DNase_II. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O00115-1 [UniParc]FASTAAdd to Basket

« Hide

MIPLLLAALL CVPAGALTCY GDSGQPVDWF VVYKLPALRG SGEAAQRGLQ    50
YKYLDESSGG WRDGRALINS PEGAVGRSLQ PLYRSNTSQL AFLLYNDQPP 100
QPSKAQDSSM RGHTKGVLLL DHDGGFWLVH SVPNFPPPAS SAAYSWPHSA 150
CTYGQTLLCV SFPFAQFSKM GKQLTYTYPW VYNYQLEGIF AQEFPDLENV 200
VKGHHVSQEP WNSSITLTSQ AGAVFQSFAK FSKFGDDLYS GWLAAALGTN 250
LQVQFWHKTV GILPSNCSDI WQVLNVNQIA FPGPAGPSFN STEDHSKWCV 300
SPKGPWTCVG DMNRNQGEEQ RGGGTLCAQL PALWKAFQPL VKNYQPCNGM 350
ARKPSRAYKI 360
Length:360
Mass (Da):39,581
Last modified:July 15, 1998 - v2
Checksum:iDF1BBFBA8A9676EA
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti39 – 391R → I.
Corresponds to variant rs36075196 [ dbSNP | Ensembl ].
VAR_048870
Natural varianti204 – 2041H → R.
Corresponds to variant rs16978744 [ dbSNP | Ensembl ].
VAR_048871
Natural varianti314 – 3141R → L.
Corresponds to variant rs1061192 [ dbSNP | Ensembl ].
VAR_012044

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti160 – 17112Missing in AAB51172. 1 PublicationAdd
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS12284.1.
PIRiJE0206.
T45071.
RefSeqiNP_001366.1. NM_001375.2.
UniGeneiHs.118243.

Genome annotation databases

EnsembliENST00000222219; ENSP00000222219; ENSG00000105612.
GeneIDi1777.
KEGGihsa:1777.
UCSCiuc002mvn.1. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS12284.1.
PIRi JE0206.
T45071.
RefSeqi NP_001366.1. NM_001375.2.
UniGenei Hs.118243.

3D structure databases

ProteinModelPortali O00115.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108116. 8 interactions.
IntActi O00115. 1 interaction.
MINTi MINT-2997367.
STRINGi 9606.ENSP00000222219.

Chemistry

BindingDBi O00115.
ChEMBLi CHEMBL1250342.

PTM databases

PhosphoSitei O00115.

Proteomic databases

MaxQBi O00115.
PaxDbi O00115.
PeptideAtlasi O00115.
PRIDEi O00115.

Protocols and materials databases

DNASUi 1777.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000222219 ; ENSP00000222219 ; ENSG00000105612 .
GeneIDi 1777.
KEGGi hsa:1777.
UCSCi uc002mvn.1. human.

Organism-specific databases

CTDi 1777.
GeneCardsi GC19M012986.
HGNCi HGNC:2960. DNASE2.
MIMi 126350. gene.
neXtProti NX_O00115.
PharmGKBi PA27431.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG145330.
HOGENOMi HOG000261682.
HOVERGENi HBG051387.
InParanoidi O00115.
KOi K01158.
OMAi NLQVQFW.
PhylomeDBi O00115.
TreeFami TF314536.

Enzyme and pathway databases

BRENDAi 3.1.22.1. 2681.
Reactomei REACT_19287. Lysosome Vesicle Biogenesis.

Miscellaneous databases

GenomeRNAii 1777.
NextBioi 7235.
PROi O00115.
SOURCEi Search...

Gene expression databases

ArrayExpressi O00115.
Bgeei O00115.
CleanExi HS_DNASE2.
Genevestigatori O00115.

Family and domain databases

InterProi IPR004947. DNase_II.
[Graphical view ]
PANTHERi PTHR10858. PTHR10858. 1 hit.
Pfami PF03265. DNase_II. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiDNS2A_HUMAN
AccessioniPrimary (citable) accession number: O00115
Secondary accession number(s): B2RD06, O43910
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 15, 1998
Last modified: September 3, 2014
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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