DNSL2_HUMAN
ID DNSL2_HUMAN Reviewed; 299 AA.
AC Q92874; E9PBY4; Q6JVM2; Q6JVM3;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Deoxyribonuclease-1-like 2;
DE EC=3.1.21.-;
DE AltName: Full=DNase I homolog protein DHP1;
DE AltName: Full=Deoxyribonuclease I-like 2;
DE Short=DNase I-like 2;
DE Flags: Precursor;
GN Name=DNASE1L2; Synonyms=DHP1, DNAS1L2;
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 [MRNA] (ISOFORM 1).
RX PubMed=9205125; DOI=10.1006/geno.1997.4748;
RA Rodriguez A.M., Rodin D., Nomura H., Morton C.C., Weremowicz S.,
RA Schneider M.C.;
RT "Identification, localization, and expression of two novel human genes
RT similar to deoxyribonuclease I.";
RL Genomics 42:507-513(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), INDUCTION,
RP COFACTOR, AND ALTERNATIVE SPLICING.
RX PubMed=15203207; DOI=10.1016/j.ygeno.2004.02.003;
RA Shiokawa D., Matsushita T., Kobayashi T., Matsumoto Y., Tanuma S.I.;
RT "Characterization of the human DNAS1L2 gene and the molecular mechanism for
RT its transcriptional activation induced by inflammatory cytokines.";
RL Genomics 84:95-105(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thymus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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 [7]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=16902420; DOI=10.1038/sj.jid.5700503;
RA Fischer H., Eckhart L., Mildner M., Jaeger K., Buchberger M., Ghannadan M.,
RA Tschachler E.;
RT "DNase1L2 degrades nuclear DNA during corneocyte formation.";
RL J. Invest. Dermatol. 127:24-30(2007).
CC -!- FUNCTION: Divalent cation-dependent acid DNA endonuclease involved in
CC the breakdown of the nucleus during corneocyte formation of epidermal
CC keratinocytes. May play an immune role by eliminating harmful DNA
CC released into the extracellular environment by damaged epidermal cells.
CC {ECO:0000269|PubMed:16902420}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15203207};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:15203207};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16902420}. Secreted
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=DNAS1L2-L;
CC IsoId=Q92874-1; Sequence=Displayed;
CC Name=2; Synonyms=DNAS1L2-S;
CC IsoId=Q92874-2; Sequence=VSP_053879;
CC -!- TISSUE SPECIFICITY: Preferentially expressed in the skin and up-
CC regulated during keratinocytes differentiation. Highly abundant (at
CC protein level) in the stratum granulosum.
CC {ECO:0000269|PubMed:16902420}.
CC -!- INDUCTION: Up-regulated by inflammatory cytokines.
CC {ECO:0000269|PubMed:15203207}.
CC -!- MISCELLANEOUS: [Isoform 2]: Specifically expressed in peripheral blood
CC leukocytes. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the DNase I family. {ECO:0000305}.
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DR EMBL; U62647; AAB63981.1; -; mRNA.
DR EMBL; AY298957; AAQ73759.1; -; mRNA.
DR EMBL; AY298958; AAQ73760.1; -; Genomic_DNA.
DR EMBL; AY298958; AAQ73761.1; -; Genomic_DNA.
DR EMBL; AK098028; BAG53566.1; -; mRNA.
DR EMBL; AC009065; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471112; EAW85526.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85527.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85528.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85529.1; -; Genomic_DNA.
DR EMBL; BC035205; AAH35205.1; -; mRNA.
DR EMBL; BC063710; AAH63710.1; -; mRNA.
DR CCDS; CCDS42105.1; -. [Q92874-1]
DR RefSeq; NP_001288609.1; NM_001301680.1. [Q92874-1]
DR RefSeq; NP_001365.1; NM_001374.2. [Q92874-1]
DR AlphaFoldDB; Q92874; -.
DR SMR; Q92874; -.
DR BioGRID; 108114; 36.
DR IntAct; Q92874; 11.
DR STRING; 9606.ENSP00000454562; -.
DR iPTMnet; Q92874; -.
DR PhosphoSitePlus; Q92874; -.
DR BioMuta; DNASE1L2; -.
DR DMDM; 2494172; -.
DR jPOST; Q92874; -.
DR MassIVE; Q92874; -.
DR PaxDb; Q92874; -.
DR PeptideAtlas; Q92874; -.
DR PRIDE; Q92874; -.
DR ProteomicsDB; 66528; -.
DR ProteomicsDB; 75558; -. [Q92874-1]
DR Antibodypedia; 51835; 61 antibodies from 13 providers.
DR DNASU; 1775; -.
DR Ensembl; ENST00000320700.10; ENSP00000316938.5; ENSG00000167968.13. [Q92874-1]
DR Ensembl; ENST00000382437.8; ENSP00000371874.4; ENSG00000167968.13. [Q92874-2]
DR Ensembl; ENST00000564065.5; ENSP00000454562.1; ENSG00000167968.13. [Q92874-1]
DR Ensembl; ENST00000567494.5; ENSP00000455358.1; ENSG00000167968.13. [Q92874-1]
DR Ensembl; ENST00000613572.4; ENSP00000482627.1; ENSG00000167968.13. [Q92874-2]
DR GeneID; 1775; -.
DR KEGG; hsa:1775; -.
DR MANE-Select; ENST00000320700.10; ENSP00000316938.5; NM_001374.3; NP_001365.1.
DR UCSC; uc002cpn.4; human. [Q92874-1]
DR CTD; 1775; -.
DR DisGeNET; 1775; -.
DR GeneCards; DNASE1L2; -.
DR HGNC; HGNC:2958; DNASE1L2.
DR HPA; ENSG00000167968; Tissue enriched (skin).
DR MIM; 602622; gene.
DR neXtProt; NX_Q92874; -.
DR OpenTargets; ENSG00000167968; -.
DR PharmGKB; PA27429; -.
DR VEuPathDB; HostDB:ENSG00000167968; -.
DR eggNOG; ENOG502SGB6; Eukaryota.
DR GeneTree; ENSGT00950000182846; -.
DR HOGENOM; CLU_043335_2_1_1; -.
DR InParanoid; Q92874; -.
DR OMA; CNYVRAQ; -.
DR OrthoDB; 1282784at2759; -.
DR PhylomeDB; Q92874; -.
DR TreeFam; TF329541; -.
DR PathwayCommons; Q92874; -.
DR SignaLink; Q92874; -.
DR BioGRID-ORCS; 1775; 10 hits in 1072 CRISPR screens.
DR ChiTaRS; DNASE1L2; human.
DR GeneWiki; DNASE1L2; -.
DR GenomeRNAi; 1775; -.
DR Pharos; Q92874; Tbio.
DR PRO; PR:Q92874; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q92874; protein.
DR Bgee; ENSG00000167968; Expressed in skin of abdomen and 106 other tissues.
DR ExpressionAtlas; Q92874; baseline and differential.
DR Genevisible; Q92874; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; TAS:ProtInc.
DR GO; GO:0004536; F:deoxyribonuclease activity; TAS:ProtInc.
DR GO; GO:0004530; F:deoxyribonuclease I activity; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR GO; GO:0003335; P:corneocyte development; IEA:Ensembl.
DR GO; GO:0006308; P:DNA catabolic process; IBA:GO_Central.
DR GO; GO:0000737; P:DNA catabolic process, endonucleolytic; IBA:GO_Central.
DR GO; GO:0006259; P:DNA metabolic process; TAS:ProtInc.
DR GO; GO:0001942; P:hair follicle development; IEA:Ensembl.
DR Gene3D; 3.60.10.10; -; 1.
DR InterPro; IPR018057; Deoxyribonuclease-1_AS.
DR InterPro; IPR016202; DNase_I.
DR InterPro; IPR033125; DNASE_I_2.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR PIRSF; PIRSF000988; DNase_I_euk; 1.
DR PRINTS; PR00130; DNASEI.
DR SMART; SM00476; DNaseIc; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
DR PROSITE; PS00919; DNASE_I_1; 1.
DR PROSITE; PS00918; DNASE_I_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cytoplasm; Disulfide bond; Endonuclease;
KW Hydrolase; Magnesium; Metal-binding; Nuclease; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..299
FT /note="Deoxyribonuclease-1-like 2"
FT /id="PRO_0000007286"
FT ACT_SITE 99
FT /evidence="ECO:0000250"
FT ACT_SITE 170
FT /evidence="ECO:0000250"
FT DISULFID 209..245
FT /note="Essential for enzymatic activity"
FT /evidence="ECO:0000250"
FT VAR_SEQ 140..160
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15203207"
FT /id="VSP_053879"
SQ SEQUENCE 299 AA; 32853 MW; 1B66A5590D33D0A6 CRC64;
MGGPRALLAA LWALEAAGTA ALRIGAFNIQ SFGDSKVSDP ACGSIIAKIL AGYDLALVQE
VRDPDLSAVS ALMEQINSVS EHEYSFVSSQ PLGRDQYKEM YLFVYRKDAV SVVDTYLYPD
PEDVFSREPF VVKFSAPGTG ERAPPLPSRR ALTPPPLPAA AQNLVLIPLH AAPHQAVAEI
DALYDVYLDV IDKWGTDDML FLGDFNADCS YVRAQDWAAI RLRSSEVFKW LIPDSADTTV
GNSDCAYDRI VACGARLRRS LKPQSATVHD FQEEFGLDQT QALAISDHFP VEVTLKFHR
