ID DNS2A_HUMAN Reviewed; 360 AA. AC O00115; B2RD06; B7Z4K6; O43910; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1998, sequence version 2. DT 13-FEB-2019, entry version 168. DE RecName: Full=Deoxyribonuclease-2-alpha; DE EC=3.1.22.1; DE AltName: Full=Acid DNase; DE AltName: Full=Deoxyribonuclease II alpha; DE Short=DNase II alpha; DE AltName: Full=Lysosomal DNase II; DE AltName: Full=R31240_2; DE Flags: Precursor; 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 [GENOMIC DNA]. RX PubMed=9924608; DOI=10.1046/j.1469-1809.1998.6240299.x; 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 [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX 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 [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX 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] (ISOFORM 1). RX 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 [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] 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 [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Muscle; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP LACK OF PROTEOLYTIC PROCESSING, AND GLYCOSYLATION. RX 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 [12] 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 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 [13] 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 [14] RP GLYCOSYLATION AT ASN-212. RX 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). RN [15] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-212. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of RT multiple enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). 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: CC Reaction=Endonucleolytic cleavage to nucleoside 3'-phosphates and CC 3'-phosphooligonucleotide end-products.; EC=3.1.22.1; CC -!- SUBCELLULAR LOCATION: Lysosome. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O00115-1; Sequence=Displayed; CC Name=2; CC IsoId=O00115-2; Sequence=VSP_056921; CC Note=No experimental confirmation available.; CC -!- PTM: Glycosylated. Mutations that eliminate N-glycosylation sites CC reduce activity, but enzymatic deglycosylation has no effect. CC {ECO:0000269|PubMed:11906178, ECO:0000269|PubMed:12558498, CC ECO:0000269|PubMed:12754519, ECO:0000269|PubMed:19159218}. 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. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the DNase II family. {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AB008564; BAB55598.1; -; Genomic_DNA. DR EMBL; AF060222; AAC39852.1; -; mRNA. DR EMBL; AF045937; AAC35751.1; -; mRNA. DR EMBL; AF047016; AAC77366.1; -; mRNA. DR EMBL; AB004574; BAA28623.1; -; mRNA. DR EMBL; BT007047; AAP35696.1; -; mRNA. DR EMBL; AK297493; BAH12592.1; -; mRNA. DR EMBL; AK315358; BAG37753.1; -; mRNA. DR EMBL; AC020934; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AD000092; AAB51172.1; -; Genomic_DNA. DR EMBL; CH471106; EAW84320.1; -; Genomic_DNA. DR EMBL; BC010419; AAH10419.3; -; mRNA. DR EMBL; BC065209; AAH65209.1; -; mRNA. DR CCDS; CCDS12284.1; -. [O00115-1] DR PIR; JE0206; JE0206. DR PIR; T45071; T45071. DR RefSeq; NP_001366.1; NM_001375.2. [O00115-1] DR UniGene; Hs.118243; -. DR ProteinModelPortal; O00115; -. DR SMR; O00115; -. DR BioGrid; 108116; 10. DR IntAct; O00115; 1. DR STRING; 9606.ENSP00000222219; -. DR BindingDB; O00115; -. DR ChEMBL; CHEMBL1250342; -. DR GlyConnect; 1170; -. DR iPTMnet; O00115; -. DR PhosphoSitePlus; O00115; -. DR BioMuta; DNASE2; -. DR EPD; O00115; -. DR jPOST; O00115; -. DR MaxQB; O00115; -. DR PaxDb; O00115; -. DR PeptideAtlas; O00115; -. DR PRIDE; O00115; -. DR ProteomicsDB; 47717; -. DR DNASU; 1777; -. DR Ensembl; ENST00000222219; ENSP00000222219; ENSG00000105612. [O00115-1] DR GeneID; 1777; -. DR KEGG; hsa:1777; -. DR UCSC; uc002mvn.2; human. [O00115-1] DR CTD; 1777; -. DR DisGeNET; 1777; -. DR EuPathDB; HostDB:ENSG00000105612.8; -. DR GeneCards; DNASE2; -. DR HGNC; HGNC:2960; DNASE2. DR HPA; HPA066185; -. DR MIM; 126350; gene. DR neXtProt; NX_O00115; -. DR OpenTargets; ENSG00000105612; -. DR PharmGKB; PA27431; -. DR eggNOG; KOG3825; Eukaryota. DR eggNOG; ENOG4111G8U; LUCA. DR GeneTree; ENSGT00390000002634; -. DR HOGENOM; HOG000261682; -. DR HOVERGEN; HBG051387; -. DR InParanoid; O00115; -. DR KO; K01158; -. DR OMA; EHRGGGT; -. DR OrthoDB; 605654at2759; -. DR PhylomeDB; O00115; -. DR TreeFam; TF314536; -. DR BRENDA; 3.1.22.1; 2681. DR Reactome; R-HSA-432720; Lysosome Vesicle Biogenesis. DR ChiTaRS; DNASE2; human. DR GenomeRNAi; 1777; -. DR PRO; PR:O00115; -. DR Proteomes; UP000005640; Chromosome 19. DR Bgee; ENSG00000105612; Expressed in 213 organ(s), highest expression level in pituitary gland. DR ExpressionAtlas; O00115; baseline and differential. DR Genevisible; O00115; HS. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005764; C:lysosome; TAS:ProtInc. DR GO; GO:0004531; F:deoxyribonuclease II activity; IBA:GO_Central. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0006309; P:apoptotic DNA fragmentation; IBA:GO_Central. DR GO; GO:0006259; P:DNA metabolic process; TAS:ProtInc. DR GO; GO:0030218; P:erythrocyte differentiation; IEA:Ensembl. DR GO; GO:0050776; P:regulation of immune response; IEA:Ensembl. DR InterPro; IPR004947; DNase_II. DR PANTHER; PTHR10858; PTHR10858; 1. DR Pfam; PF03265; DNase_II; 1. PE 1: Evidence at protein level; KW Alternative splicing; Apoptosis; Complete proteome; KW Developmental protein; Disulfide bond; Endonuclease; Glycoprotein; KW Hydrolase; Lysosome; Nuclease; Polymorphism; Reference proteome; KW Signal. FT SIGNAL 1 18 {ECO:0000255}. FT CHAIN 19 360 Deoxyribonuclease-2-alpha. FT /FTId=PRO_0000007291. FT ACT_SITE 295 295 {ECO:0000305}. FT CARBOHYD 86 86 N-linked (GlcNAc...) asparagine. FT CARBOHYD 212 212 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:19159218}. FT CARBOHYD 266 266 N-linked (GlcNAc...) asparagine. FT CARBOHYD 290 290 N-linked (GlcNAc...) asparagine. FT DISULFID 19 159 {ECO:0000255}. FT DISULFID 267 347 {ECO:0000255}. FT DISULFID 308 327 {ECO:0000255}. FT VAR_SEQ 116 170 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_056921. FT VARIANT 39 39 R -> I (in dbSNP:rs36075196). FT /FTId=VAR_048870. FT VARIANT 204 204 H -> R (in dbSNP:rs16978744). FT /FTId=VAR_048871. FT VARIANT 314 314 R -> L (in dbSNP:rs1061192). FT /FTId=VAR_012044. FT MUTAGEN 19 19 C->A: Loss of activity. FT {ECO:0000269|PubMed:12558498}. 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 {ECO:0000269|PubMed:12558498}. FT MUTAGEN 151 151 C->A: Loss of activity. FT {ECO:0000269|PubMed:12558498}. FT MUTAGEN 159 159 C->A: Loss of activity. FT {ECO:0000269|PubMed:12558498}. 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 {ECO:0000269|PubMed:12558498}. 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 {ECO:0000269|PubMed:12558498}. FT MUTAGEN 267 267 C->A: Loss of activity. FT {ECO:0000269|PubMed:12558498}. 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 {ECO:0000269|PubMed:12558498}. FT MUTAGEN 295 295 H->A,K,N,R,S: Loss of activity, but not FT of DNA-binding. FT {ECO:0000269|PubMed:12594037}. FT MUTAGEN 299 299 C->A: No effect. FT {ECO:0000269|PubMed:12558498}. FT MUTAGEN 308 308 C->A: Loss of activity. FT {ECO:0000269|PubMed:12558498}. FT MUTAGEN 327 327 C->A: Loss of activity. FT {ECO:0000269|PubMed:12558498}. FT MUTAGEN 347 347 C->A: Loss of activity. FT {ECO:0000269|PubMed:12558498}. FT CONFLICT 160 171 Missing (in Ref. 8; AAB51172). FT {ECO:0000305}. 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 //