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 27-MAR-2024, entry version 194. DE RecName: Full=Deoxyribonuclease-2-alpha; DE EC=3.1.22.1 {ECO:0000269|PubMed:29259162, ECO:0000269|PubMed:31775019}; 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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC 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 II) RT 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 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 role RT 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., Nakashima Y., RA 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 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., 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., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., 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 project: RT 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 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; CYS-267; RP ASN-290; CYS-299; CYS-308; CYS-327 AND CYS-347, GLYCOSYLATION, AND RP 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 multiple RT 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., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT 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., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [18] RP INVOLVEMENT IN AIPCS, VARIANTS AIPCS ALA-116 AND VAL-121, FUNCTION, AND RP TISSUE SPECIFICITY. RX PubMed=29259162; DOI=10.1038/s41467-017-01932-3; RA Rodero M.P., Tesser A., Bartok E., Rice G.I., Della Mina E., Depp M., RA Beitz B., Bondet V., Cagnard N., Duffy D., Dussiot M., Fremond M.L., RA Gattorno M., Guillem F., Kitabayashi N., Porcheray F., Rieux-Laucat F., RA Seabra L., Uggenti C., Volpi S., Zeef L.A.H., Alyanakian M.A., Beltrand J., RA Bianco A.M., Boddaert N., Brouzes C., Candon S., Caorsi R., Charbit M., RA Fabre M., Faletra F., Girard M., Harroche A., Hartmann E., Lasne D., RA Marcuzzi A., Neven B., Nitschke P., Pascreau T., Pastore S., Picard C., RA Picco P., Piscianz E., Polak M., Quartier P., Rabant M., Stocco G., RA Taddio A., Uettwiller F., Valencic E., Vozzi D., Hartmann G., Barchet W., RA Hermine O., Bader-Meunier B., Tommasini A., Crow Y.J.; RT "Type I interferon-mediated autoinflammation due to DNase II deficiency."; RL Nat. Commun. 8:2176-2176(2017). RN [19] RP INVOLVEMENT IN AIPCS, VARIANT AIPCS CYS-95, CHARACTERIZATION OF VARIANT RP AIPCS CYS-95, AND FUNCTION. RX PubMed=31775019; DOI=10.1016/j.jaci.2019.11.020; RA Hong Y., Capitani M., Murphy C., Pandey S., Cavounidis A., Takeshita H., RA Nanthapisal S., Yasuda T., Bader-Meunier B., McCreary D., Omoyinmi E., RA Rao A., Booth C., Gilmour K., Sebire N., Shah N., Klein N., Bullock A.N., RA Eleftheriou D., Uhlig H.H., Brogan P.; RT "Janus kinase inhibition for autoinflammation in patients with DNASE2 RT deficiency."; RL J. Allergy Clin. Immunol. 145:701-705(2020). CC -!- FUNCTION: Hydrolyzes DNA under acidic conditions with a preference for CC double-stranded DNA. Plays a major role in the clearance of nucleic CC acids generated through apoptosis, hence preventing autoinflammation CC (PubMed:29259162, PubMed:31775019). Necessary for proper fetal CC development and for definitive erythropoiesis in fetal liver and bone CC marrow, where it degrades nuclear DNA expelled from erythroid precursor CC cells (PubMed:29259162). {ECO:0000269|PubMed:29259162, CC ECO:0000269|PubMed:31775019}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Endonucleolytic cleavage to nucleoside 3'-phosphates and 3'- CC phosphooligonucleotide end-products.; EC=3.1.22.1; CC Evidence={ECO:0000269|PubMed:29259162, ECO:0000269|PubMed:31775019}; 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 -!- TISSUE SPECIFICITY: Expressed in monocytes/macrophages (at protein CC level). {ECO:0000269|PubMed:29259162}. CC -!- PTM: Glycosylated. Genetic variations that affect 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 -!- DISEASE: Autoinflammatory-pancytopenia syndrome (AIPCS) [MIM:619858]: CC An autosomal recessive disorder characterized by severe anemia and CC thrombocytopenia apparent from early infancy, hepatosplenomegaly, and CC recurrent fevers associated with a hyperinflammatory state. Additional CC systemic features may include chronic diarrhea, proteinuria with renal CC disease, liver fibrosis with elevated liver enzymes, deforming CC arthropathy, and vasculitic skin lesions. Some patients may have motor CC delay or learning difficulties associated with subcortical white matter CC lesions on brain imaging. {ECO:0000269|PubMed:29259162, CC ECO:0000269|PubMed:31775019}. Note=The disease is caused by variants CC affecting the gene represented in this entry. The genetic variation CC producing the missense variant p.G116A, associated with AIPCS, has been CC shown to predominantly affect splicing, leading to in-frame deletion of CC exon 4, encoding amino acids 116 to 171. The protein resulting from CC this aberrant splicing may be unstable. {ECO:0000269|PubMed:29259162}. 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 AlphaFoldDB; O00115; -. DR SMR; O00115; -. DR BioGRID; 108116; 26. DR IntAct; O00115; 2. DR STRING; 9606.ENSP00000222219; -. DR BindingDB; O00115; -. DR ChEMBL; CHEMBL1250342; -. DR GlyConnect; 1170; 2 N-Linked glycans (2 sites). DR GlyCosmos; O00115; 4 sites, 2 glycans. DR GlyGen; O00115; 4 sites, 2 N-linked glycans (2 sites). DR iPTMnet; O00115; -. DR PhosphoSitePlus; O00115; -. DR SwissPalm; O00115; -. DR BioMuta; DNASE2; -. DR EPD; O00115; -. DR jPOST; O00115; -. DR MassIVE; O00115; -. DR MaxQB; O00115; -. DR PaxDb; 9606-ENSP00000222219; -. DR PeptideAtlas; O00115; -. DR ProteomicsDB; 47717; -. [O00115-1] DR ProteomicsDB; 6606; -. DR Pumba; O00115; -. DR Antibodypedia; 13408; 266 antibodies from 32 providers. DR DNASU; 1777; -. DR Ensembl; ENST00000222219.8; ENSP00000222219.2; ENSG00000105612.10. [O00115-1] DR Ensembl; ENST00000592506.2; ENSP00000466912.2; ENSG00000105612.10. [O00115-2] DR GeneID; 1777; -. DR KEGG; hsa:1777; -. DR MANE-Select; ENST00000222219.8; ENSP00000222219.2; NM_001375.3; NP_001366.1. DR UCSC; uc002mvn.2; human. [O00115-1] DR AGR; HGNC:2960; -. DR CTD; 1777; -. DR DisGeNET; 1777; -. DR GeneCards; DNASE2; -. DR HGNC; HGNC:2960; DNASE2. DR HPA; ENSG00000105612; Low tissue specificity. DR MalaCards; DNASE2; -. DR MIM; 126350; gene. DR MIM; 619858; phenotype. DR neXtProt; NX_O00115; -. DR OpenTargets; ENSG00000105612; -. DR PharmGKB; PA27431; -. DR VEuPathDB; HostDB:ENSG00000105612; -. DR eggNOG; KOG3825; Eukaryota. DR GeneTree; ENSGT00390000002634; -. DR HOGENOM; CLU_053867_0_1_1; -. DR InParanoid; O00115; -. DR OMA; EGPWACV; -. DR OrthoDB; 4662at2759; -. DR PhylomeDB; O00115; -. DR TreeFam; TF314536; -. DR BRENDA; 3.1.22.1; 2681. DR PathwayCommons; O00115; -. DR Reactome; R-HSA-432720; Lysosome Vesicle Biogenesis. DR SignaLink; O00115; -. DR BioGRID-ORCS; 1777; 45 hits in 1163 CRISPR screens. DR ChiTaRS; DNASE2; human. DR GenomeRNAi; 1777; -. DR Pharos; O00115; Tbio. DR PRO; PR:O00115; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; O00115; Protein. DR Bgee; ENSG00000105612; Expressed in pancreatic ductal cell and 182 other cell types or tissues. DR ExpressionAtlas; O00115; baseline and differential. 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:0043353; P:enucleate erythrocyte differentiation; IEA:Ensembl. DR GO; GO:0050776; P:regulation of immune response; IEA:Ensembl. DR CDD; cd09189; PLDc_DNaseII_alpha_1; 1. DR CDD; cd09191; PLDc_DNaseII_alpha_2; 1. DR InterPro; IPR004947; DNase_II. DR PANTHER; PTHR10858; DEOXYRIBONUCLEASE II; 1. DR PANTHER; PTHR10858:SF9; DEOXYRIBONUCLEASE-2-ALPHA; 1. DR Pfam; PF03265; DNase_II; 1. DR Genevisible; O00115; HS. PE 1: Evidence at protein level; KW Alternative splicing; Apoptosis; Developmental protein; Disease variant; KW Disulfide bond; Endonuclease; Glycoprotein; Hydrolase; Lysosome; Nuclease; KW Reference proteome; Signal. FT SIGNAL 1..18 FT /evidence="ECO:0000255" FT CHAIN 19..360 FT /note="Deoxyribonuclease-2-alpha" FT /id="PRO_0000007291" FT ACT_SITE 295 FT /evidence="ECO:0000305" FT CARBOHYD 86 FT /note="N-linked (GlcNAc...) asparagine" FT CARBOHYD 212 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:19159218" FT CARBOHYD 266 FT /note="N-linked (GlcNAc...) asparagine" FT CARBOHYD 290 FT /note="N-linked (GlcNAc...) asparagine" FT DISULFID 19..159 FT /evidence="ECO:0000255" FT DISULFID 267..347 FT /evidence="ECO:0000255" FT DISULFID 308..327 FT /evidence="ECO:0000255" FT VAR_SEQ 116..170 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056921" FT VARIANT 39 FT /note="R -> I (in dbSNP:rs36075196)" FT /id="VAR_048870" FT VARIANT 95 FT /note="Y -> C (in AIPCS; complete loss of DNase activity in FT a single radial enzyme diffusion assay, confirmed by FT deficiency in DNA degradation in the granulocytes of a FT homozygous patient; no effect on expression level; FT dbSNP:rs201030953)" FT /evidence="ECO:0000269|PubMed:31775019" FT /id="VAR_087103" FT VARIANT 116 FT /note="G -> A (in AIPCS; the genetic variation producing FT this missense variant predominantly affects splicing and FT the protein resulting from this aberrant splicing may be FT unstable; reduced DNase activity)" FT /evidence="ECO:0000269|PubMed:29259162" FT /id="VAR_087104" FT VARIANT 121 FT /note="D -> V (in AIPCS; reduced DNase activity)" FT /evidence="ECO:0000269|PubMed:29259162" FT /id="VAR_087105" FT VARIANT 204 FT /note="H -> R (in dbSNP:rs16978744)" FT /id="VAR_048871" FT VARIANT 314 FT /note="R -> L (in dbSNP:rs1061192)" FT /id="VAR_012044" FT MUTAGEN 19 FT /note="C->A: Loss of activity." FT /evidence="ECO:0000269|PubMed:12558498" FT MUTAGEN 86 FT /note="N->Q: Reduced N-glycosylation, complete loss of FT N-glycosylation; when associated with Q-212; Q-266 and FT Q-290." FT /evidence="ECO:0000269|PubMed:12558498" FT MUTAGEN 151 FT /note="C->A: Loss of activity." FT /evidence="ECO:0000269|PubMed:12558498" FT MUTAGEN 159 FT /note="C->A: Loss of activity." FT /evidence="ECO:0000269|PubMed:12558498" FT MUTAGEN 212 FT /note="N->Q: Reduced N-glycosylation, complete loss of FT N-glycosylation; when associated with Q-86; Q-266 and FT Q-290." FT /evidence="ECO:0000269|PubMed:12558498" FT MUTAGEN 266 FT /note="N->Q: Reduced N-glycosylation, complete loss of FT N-glycosylation; when associated with Q-86; Q-212 and FT Q-290." FT /evidence="ECO:0000269|PubMed:12558498" FT MUTAGEN 267 FT /note="C->A: Loss of activity." FT /evidence="ECO:0000269|PubMed:12558498" FT MUTAGEN 290 FT /note="N->Q: Reduced N-glycosylation, complete loss of FT N-glycosylation; when associated with Q-86; Q-212 and FT Q-266." FT /evidence="ECO:0000269|PubMed:12558498" FT MUTAGEN 295 FT /note="H->A,K,N,R,S: Loss of activity, but not of FT DNA-binding." FT /evidence="ECO:0000269|PubMed:12594037" FT MUTAGEN 299 FT /note="C->A: No effect." FT /evidence="ECO:0000269|PubMed:12558498" FT MUTAGEN 308 FT /note="C->A: Loss of activity." FT /evidence="ECO:0000269|PubMed:12558498" FT MUTAGEN 327 FT /note="C->A: Loss of activity." FT /evidence="ECO:0000269|PubMed:12558498" FT MUTAGEN 347 FT /note="C->A: Loss of activity." FT /evidence="ECO:0000269|PubMed:12558498" FT CONFLICT 160..171 FT /note="Missing (in Ref. 8; AAB51172)" FT /evidence="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 //