ID DNS2A_HUMAN STANDARD; PRT; 360 AA. AC O00115; O43910; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1998, sequence version 2. DT 16-MAY-2006, entry version 54. DE Deoxyribonuclease-2-alpha precursor (EC 3.1.22.1) (Deoxyribonuclease DE II alpha) (DNase II alpha) (Acid DNase) (Lysosomal DNase II) DE (R31240_2). GN Name=DNASE2; Synonyms=DNASE2A, DNL2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=98112802; PubMed=9446563; DOI=10.1074/jbc.273.5.2610; RA Yasuda T., Takeshita H., Iida R., Nakajima T., Hosomi O., RA Nakashima Y., Kishi K.; RT "Molecular cloning of the cDNA encoding human deoxyribonuclease II."; RL J. Biol. Chem. 273:2610-2616(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=99030349; PubMed=9812984; DOI=10.1074/jbc.273.47.30909; RA Krieser R.J., Eastman A.; RT "The cloning and expression of human deoxyribonuclease II. A possible RT role in apoptosis."; RL J. Biol. Chem. 273:30909-30914(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=98382521; PubMed=9714827; DOI=10.1016/S0378-1119(98)00280-7; RA Baker K.P., Baron W.F., Henzel W.J., Spencer S.A.; RT "Molecular cloning and characterization of human and murine DNase RT II."; RL Gene 215:281-289(1998). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=98321218; PubMed=9647784; DOI=10.1006/bbrc.1998.8839; RA Shiokawa D., Tanuma S.; RT "Cloning of cDNAs encoding porcine and human DNase II."; RL Biochem. Biophys. Res. Commun. 247:864-869(1998). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=99123683; PubMed=9924608; RA Yasuda T., Takeshita H., Iida R., Tsutsumi S., Nakajima T., Hosomi O., RA Nakashima Y., Mori S., Kishi K.; RT "Structure and organization of the human deoxyribonuclease II (DNase RT II) gene."; RL Ann. Hum. Genet. 62:299-305(1998). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M., RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Muscle; RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length human RT and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [9] RP ABSENCE OF PROTEOLYTIC PROCESSING, AND GLYCOSYLATION. RX MEDLINE=21903770; PubMed=11906178; DOI=10.1006/bbrc.2002.6687; RA MacLea K.S., Krieser R.J., Eastman A.; RT "Revised structure of the active form of human deoxyribonuclease RT IIalpha."; RL Biochem. Biophys. Res. Commun. 292:415-421(2002). RN [10] RP MUTAGENESIS OF CYS-19; ASN-86; CYS-151; CYS-159; ASN-212; ASN-266; RP CYS-267; ASN-290; CYS-299; CYS-308; CYS-327 AND CYS-347, RP GLYCOSYLATION, AND DISULFIDE BONDS. RX MEDLINE=22588124; PubMed=12558498; DOI=10.1042/BJ20021875; RA MacLea K.S., Krieser R.J., Eastman A.; RT "Structural requirements of human DNase II alpha for formation of the RT active enzyme: the role of the signal peptide, N-glycosylation, and RT disulphide bridging."; RL Biochem. J. 371:867-876(2003). RN [11] RP MUTAGENESIS OF HIS-295. RX PubMed=12594037; DOI=10.1016/S0378-1119(02)01233-7; RA MacLea K.S., Krieser R.J., Eastman A.; RT "A family history of deoxyribonuclease II: surprises from Trichinella RT spiralis and Burkholderia pseudomallei."; RL Gene 305:1-12(2003). RN [12] RP GLYCOSYLATION AT ASN-212. RX MEDLINE=22660472; PubMed=12754519; DOI=10.1038/nbt827; RA Zhang H., Li X.-J., Martin D.B., Aebersold R.; RT "Identification and quantification of N-linked glycoproteins using RT hydrazide chemistry, stable isotope labeling and mass spectrometry."; RL Nat. Biotechnol. 21:660-666(2003). CC -!- FUNCTION: Hydrolyzes DNA under acidic conditions with a preference CC for double-stranded DNA. Plays a major role in the degradation of CC nuclear DNA in cellular apoptosis during development. Necessary CC for proper fetal development and for definitive erythropoiesis in CC fetal liver, where it degrades nuclear DNA expelled from erythroid CC precursor cells. CC -!- CATALYTIC ACTIVITY: Endonucleolytic cleavage to nucleoside CC 3'-phosphates and 3'-phosphooligonucleotide end-products. CC -!- SUBCELLULAR LOCATION: Lysosome. CC -!- PTM: Glycosylated. Mutations that eliminate N-glycosylation sites CC reduce activity, but enzymatic deglycosylation has no effect. CC -!- MISCELLANEOUS: Not required for the generation of the CC characteristic DNA fragmentation observed in apoptotic cells, but CC for the degradation of DNA from dying cells (By similarity). CC -!- SIMILARITY: Belongs to the DNase II family. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AB004574; BAA28623.1; -; mRNA. DR EMBL; AF047016; AAC77366.1; -; mRNA. DR EMBL; AF045937; AAC35751.1; -; mRNA. DR EMBL; AF060222; AAC39852.1; -; mRNA. DR EMBL; AB008564; BAB55598.1; -; Genomic_DNA. DR EMBL; BT007047; AAP35696.1; -; mRNA. DR EMBL; AD000092; AAB51172.1; -; Genomic_DNA. DR EMBL; BC010419; AAH10419.2; ALT_INIT; mRNA. DR EMBL; BC065209; AAH65209.1; -; mRNA. DR PIR; JE0206; JE0206. DR UniGene; Hs.118243; -. DR Ensembl; ENSG00000105612; Homo sapiens. DR HGNC; HGNC:2960; DNASE2. DR H-InvDB; HIX0014809; -. DR MIM; 126350; gene. DR GO; GO:0005764; C:lysosome; TAS. DR GO; GO:0004531; F:deoxyribonuclease II activity; TAS. DR GO; GO:0003677; F:DNA binding; TAS. DR GO; GO:0006259; P:DNA metabolism; TAS. DR InterPro; IPR004947; DNase_II. DR PANTHER; PTHR10858; DNase_II; 1. DR Pfam; PF03265; DNase_II; 1. KW Apoptosis; Developmental protein; Endonuclease; Glycoprotein; KW Hydrolase; Lysosome; Nuclease; Polymorphism; Signal. FT SIGNAL 1 18 Potential. FT CHAIN 19 360 Deoxyribonuclease-2-alpha. FT /FTId=PRO_0000007291. FT ACT_SITE 295 295 Probable. FT CARBOHYD 86 86 N-linked (GlcNAc...). FT CARBOHYD 212 212 N-linked (GlcNAc...). FT CARBOHYD 266 266 N-linked (GlcNAc...). FT CARBOHYD 290 290 N-linked (GlcNAc...). FT DISULFID 19 159 Potential. FT DISULFID 267 347 Potential. FT DISULFID 308 327 Potential. FT VARIANT 314 314 R -> L (in dbSNP:1061192). FT /FTId=VAR_012044. FT MUTAGEN 19 19 C->A: Loss of activity. FT MUTAGEN 86 86 N->Q: Reduced N-glycosylation, complete FT loss of N-glycosylation; when associated FT with Q-212; Q-266 and Q-290. FT MUTAGEN 151 151 C->A: Loss of activity. FT MUTAGEN 159 159 C->A: Loss of activity. FT MUTAGEN 212 212 N->Q: Reduced N-glycosylation, complete FT loss of N-glycosylation; when associated FT with Q-86; Q-266 and Q-290. FT MUTAGEN 266 266 N->Q: Reduced N-glycosylation, complete FT loss of N-glycosylation; when associated FT with Q-86; Q-212 and Q-290. FT MUTAGEN 267 267 C->A: Loss of activity. FT MUTAGEN 290 290 N->Q: Reduced N-glycosylation, complete FT loss of N-glycosylation; when associated FT with Q-86; Q-212 and Q-266. FT MUTAGEN 295 295 H->A,K,N,R,S: Loss of activity, but not FT of DNA-binding. FT MUTAGEN 299 299 C->A: No effect. FT MUTAGEN 308 308 C->A: Loss of activity. FT MUTAGEN 327 327 C->A: Loss of activity. FT MUTAGEN 347 347 C->A: Loss of activity. FT CONFLICT 160 171 Missing (in Ref. 7). SQ SEQUENCE 360 AA; 39581 MW; DF1BBFBA8A9676EA CRC64; MIPLLLAALL CVPAGALTCY GDSGQPVDWF VVYKLPALRG SGEAAQRGLQ YKYLDESSGG WRDGRALINS PEGAVGRSLQ PLYRSNTSQL AFLLYNDQPP QPSKAQDSSM RGHTKGVLLL DHDGGFWLVH SVPNFPPPAS SAAYSWPHSA CTYGQTLLCV SFPFAQFSKM GKQLTYTYPW VYNYQLEGIF AQEFPDLENV VKGHHVSQEP WNSSITLTSQ AGAVFQSFAK FSKFGDDLYS GWLAAALGTN LQVQFWHKTV GILPSNCSDI WQVLNVNQIA FPGPAGPSFN STEDHSKWCV SPKGPWTCVG DMNRNQGEEQ RGGGTLCAQL PALWKAFQPL VKNYQPCNGM ARKPSRAYKI //