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Protein

Deoxyribonuclease-2-alpha

Gene

DNASE2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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)DescriptionActionsGraphical viewLength
Active sitei295Curated1

GO - Molecular functioni

  • deoxyribonuclease II activity Source: ProtInc
  • DNA binding Source: ProtInc

GO - Biological processi

  • apoptotic DNA fragmentation Source: GO_Central
  • DNA metabolic process Source: ProtInc
  • erythrocyte differentiation Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Endonuclease, Hydrolase, Nuclease

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

BioCyciZFISH:HS02772-MONOMER.
BRENDAi3.1.22.1. 2681.
ReactomeiR-HSA-432720. 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
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:2960. DNASE2.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • lysosome Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Lysosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi19C → A: Loss of activity. 1 Publication1
Mutagenesisi86N → Q: Reduced N-glycosylation, complete loss of N-glycosylation; when associated with Q-212; Q-266 and Q-290. 1 Publication1
Mutagenesisi151C → A: Loss of activity. 1 Publication1
Mutagenesisi159C → A: Loss of activity. 1 Publication1
Mutagenesisi212N → Q: Reduced N-glycosylation, complete loss of N-glycosylation; when associated with Q-86; Q-266 and Q-290. 1 Publication1
Mutagenesisi266N → Q: Reduced N-glycosylation, complete loss of N-glycosylation; when associated with Q-86; Q-212 and Q-290. 1 Publication1
Mutagenesisi267C → A: Loss of activity. 1 Publication1
Mutagenesisi290N → Q: Reduced N-glycosylation, complete loss of N-glycosylation; when associated with Q-86; Q-212 and Q-266. 1 Publication1
Mutagenesisi295H → A, K, N, R or S: Loss of activity, but not of DNA-binding. 1 Publication1
Mutagenesisi299C → A: No effect. 1 Publication1
Mutagenesisi308C → A: Loss of activity. 1 Publication1
Mutagenesisi327C → A: Loss of activity. 1 Publication1
Mutagenesisi347C → A: Loss of activity. 1 Publication1

Organism-specific databases

DisGeNETi1777.
OpenTargetsiENSG00000105612.
PharmGKBiPA27431.

Chemistry databases

ChEMBLiCHEMBL1250342.

Polymorphism and mutation databases

BioMutaiDNASE2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000000729119 – 360Deoxyribonuclease-2-alphaAdd BLAST342

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi19 ↔ 159Sequence analysis
Glycosylationi86N-linked (GlcNAc...)1
Glycosylationi212N-linked (GlcNAc...)2 Publications1
Glycosylationi266N-linked (GlcNAc...)1
Disulfide bondi267 ↔ 347Sequence analysis
Glycosylationi290N-linked (GlcNAc...)1
Disulfide bondi308 ↔ 327Sequence analysis

Post-translational modificationi

Glycosylated. Mutations that eliminate N-glycosylation sites reduce activity, but enzymatic deglycosylation has no effect.4 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiO00115.
MaxQBiO00115.
PaxDbiO00115.
PeptideAtlasiO00115.
PRIDEiO00115.

PTM databases

iPTMnetiO00115.
PhosphoSitePlusiO00115.

Expressioni

Gene expression databases

BgeeiENSG00000105612.
CleanExiHS_DNASE2.
ExpressionAtlasiO00115. baseline and differential.
GenevisibleiO00115. HS.

Organism-specific databases

HPAiHPA066185.

Interactioni

Protein-protein interaction databases

BioGridi108116. 8 interactors.
IntActiO00115. 1 interactor.
MINTiMINT-2997367.
STRINGi9606.ENSP00000222219.

Chemistry databases

BindingDBiO00115.

Structurei

3D structure databases

ProteinModelPortaliO00115.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the DNase II family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3825. Eukaryota.
ENOG4111G8U. LUCA.
GeneTreeiENSGT00390000002634.
HOGENOMiHOG000261682.
HOVERGENiHBG051387.
InParanoidiO00115.
KOiK01158.
OMAiLQVQFWQ.
OrthoDBiEOG091G08N7.
PhylomeDBiO00115.
TreeFamiTF314536.

Family and domain databases

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

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O00115-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MIPLLLAALL CVPAGALTCY GDSGQPVDWF VVYKLPALRG SGEAAQRGLQ
60 70 80 90 100
YKYLDESSGG WRDGRALINS PEGAVGRSLQ PLYRSNTSQL AFLLYNDQPP
110 120 130 140 150
QPSKAQDSSM RGHTKGVLLL DHDGGFWLVH SVPNFPPPAS SAAYSWPHSA
160 170 180 190 200
CTYGQTLLCV SFPFAQFSKM GKQLTYTYPW VYNYQLEGIF AQEFPDLENV
210 220 230 240 250
VKGHHVSQEP WNSSITLTSQ AGAVFQSFAK FSKFGDDLYS GWLAAALGTN
260 270 280 290 300
LQVQFWHKTV GILPSNCSDI WQVLNVNQIA FPGPAGPSFN STEDHSKWCV
310 320 330 340 350
SPKGPWTCVG DMNRNQGEEQ RGGGTLCAQL PALWKAFQPL VKNYQPCNGM
360
ARKPSRAYKI
Length:360
Mass (Da):39,581
Last modified:July 15, 1998 - v2
Checksum:iDF1BBFBA8A9676EA
GO
Isoform 2 (identifier: O00115-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     116-170: Missing.

Note: No experimental confirmation available.
Show »
Length:305
Mass (Da):33,615
Checksum:i85A0DD26EC28FE2C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti160 – 171Missing in AAB51172 (PubMed:15057824).CuratedAdd BLAST12

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04887039R → I.Corresponds to variant rs36075196dbSNPEnsembl.1
Natural variantiVAR_048871204H → R.Corresponds to variant rs16978744dbSNPEnsembl.1
Natural variantiVAR_012044314R → L.Corresponds to variant rs1061192dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056921116 – 170Missing in isoform 2. 1 PublicationAdd BLAST55

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.
AK297493 mRNA. Translation: BAH12592.1.
AK315358 mRNA. Translation: BAG37753.1.
AC020934 Genomic DNA. No translation available.
AD000092 Genomic DNA. Translation: AAB51172.1.
CH471106 Genomic DNA. Translation: EAW84320.1.
BC010419 mRNA. Translation: AAH10419.3.
BC065209 mRNA. Translation: AAH65209.1.
CCDSiCCDS12284.1. [O00115-1]
PIRiJE0206.
T45071.
RefSeqiNP_001366.1. NM_001375.2. [O00115-1]
UniGeneiHs.118243.

Genome annotation databases

EnsembliENST00000222219; ENSP00000222219; ENSG00000105612. [O00115-1]
GeneIDi1777.
KEGGihsa:1777.
UCSCiuc002mvn.2. human. [O00115-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.
AK297493 mRNA. Translation: BAH12592.1.
AK315358 mRNA. Translation: BAG37753.1.
AC020934 Genomic DNA. No translation available.
AD000092 Genomic DNA. Translation: AAB51172.1.
CH471106 Genomic DNA. Translation: EAW84320.1.
BC010419 mRNA. Translation: AAH10419.3.
BC065209 mRNA. Translation: AAH65209.1.
CCDSiCCDS12284.1. [O00115-1]
PIRiJE0206.
T45071.
RefSeqiNP_001366.1. NM_001375.2. [O00115-1]
UniGeneiHs.118243.

3D structure databases

ProteinModelPortaliO00115.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108116. 8 interactors.
IntActiO00115. 1 interactor.
MINTiMINT-2997367.
STRINGi9606.ENSP00000222219.

Chemistry databases

BindingDBiO00115.
ChEMBLiCHEMBL1250342.

PTM databases

iPTMnetiO00115.
PhosphoSitePlusiO00115.

Polymorphism and mutation databases

BioMutaiDNASE2.

Proteomic databases

EPDiO00115.
MaxQBiO00115.
PaxDbiO00115.
PeptideAtlasiO00115.
PRIDEiO00115.

Protocols and materials databases

DNASUi1777.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000222219; ENSP00000222219; ENSG00000105612. [O00115-1]
GeneIDi1777.
KEGGihsa:1777.
UCSCiuc002mvn.2. human. [O00115-1]

Organism-specific databases

CTDi1777.
DisGeNETi1777.
GeneCardsiDNASE2.
HGNCiHGNC:2960. DNASE2.
HPAiHPA066185.
MIMi126350. gene.
neXtProtiNX_O00115.
OpenTargetsiENSG00000105612.
PharmGKBiPA27431.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3825. Eukaryota.
ENOG4111G8U. LUCA.
GeneTreeiENSGT00390000002634.
HOGENOMiHOG000261682.
HOVERGENiHBG051387.
InParanoidiO00115.
KOiK01158.
OMAiLQVQFWQ.
OrthoDBiEOG091G08N7.
PhylomeDBiO00115.
TreeFamiTF314536.

Enzyme and pathway databases

BioCyciZFISH:HS02772-MONOMER.
BRENDAi3.1.22.1. 2681.
ReactomeiR-HSA-432720. Lysosome Vesicle Biogenesis.

Miscellaneous databases

ChiTaRSiDNASE2. human.
GenomeRNAii1777.
PROiO00115.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105612.
CleanExiHS_DNASE2.
ExpressionAtlasiO00115. baseline and differential.
GenevisibleiO00115. HS.

Family and domain databases

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

Entry informationi

Entry nameiDNS2A_HUMAN
AccessioniPrimary (citable) accession number: O00115
Secondary accession number(s): B2RD06, B7Z4K6, O43910
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 15, 1998
Last modified: November 2, 2016
This is version 150 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.