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O00115

- DNS2A_HUMAN

UniProt

O00115 - DNS2A_HUMAN

Protein

Deoxyribonuclease-2-alpha

Gene

DNASE2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 127 (01 Oct 2014)
      Sequence version 2 (15 Jul 1998)
      Previous versions | rss
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    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 – 2951Curated

    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

    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

    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 – 1818Sequence AnalysisAdd
    BLAST
    Chaini19 – 360342Deoxyribonuclease-2-alphaPRO_0000007291Add
    BLAST

    Amino acid modifications

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

    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the DNase II family.Curated

    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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti160 – 17112Missing in AAB51172. (PubMed:15057824)CuratedAdd
    BLAST

    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 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

    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: October 1, 2014
    This is version 127 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