Q13609 (DNSL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Deoxyribonuclease gamma
Short name=DNase gamma
EC=3.1.21.-

Alternative name(s):
DNase I homolog protein DHP2
Deoxyribonuclease I-like 3
Short name=DNase I-like 3
Liver and spleen DNase
Short name=LS-DNase
Short name=LSD

Gene names

Name:	DNASE1L3
Synonyms:	DHP2, DNAS1L3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	305 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Has DNA hydrolytic activity. Does not bind to actin. Cleaves chromatin DNA to nucleosomal units.
Cofactor	Calcium. Magnesium.
Enzyme regulation	Inhibited by zinc.
Subcellular location	Nucleus. Note: May first pass through the ER membrane before being imported in the nucleus.
Tissue specificity	Liver and spleen.
Involvement in disease	Systemic lupus erythematosus 16 (SLEB16) [MIM:614420]: A rare autosomal recessive form of systemic lupus erythematosus with childhood onset, characterized by high frequency of anti-neutrophil cytoplasmic antibodies and lupus nephritis. Systemic lupus erythematosus is a chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8
Sequence similarities	Belongs to the DNase I family.
Biophysicochemical properties	pH dependence: Optimum pH is about 7.2.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Systemic lupus erythematosus
Domain	Signal
Ligand	Calcium
Molecular function	Endonuclease Hydrolase Nuclease
PTM	Disulfide bond
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA metabolic process Traceable author statement Ref.2. Source: ProtInc apoptotic DNA fragmentation Inferred from electronic annotation. Source: Compara
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	DNA binding Traceable author statement Ref.2. Source: ProtInc calcium ion binding Traceable author statement Ref.1. Source: ProtInc deoxyribonuclease activity Traceable author statement Ref.2. Source: ProtInc endodeoxyribonuclease activity, producing 5'-phosphomonoesters Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	By similarity
	Chain	21 – 305	285	Deoxyribonuclease gamma		PRO_0000007288
Regions
	Motif	35 – 51	17	Bipartite nuclear localization signal Potential
	Motif	296 – 304	9	Nuclear localization signal Potential
Sites
	Active site	100	1	By similarity
	Active site	155	1	By similarity
Amino acid modifications
	Disulfide bond	194 ↔ 231		Essential for enzymatic activity By similarity
Natural variations
	Natural variant	19	1	L → V in a breast cancer sample; somatic mutation. Ref.9		VAR_036079
	Natural variant	82	1	G → R in a breast cancer sample; somatic mutation. Ref.9		VAR_036080
	Natural variant	96	1	N → K. Ref.4 Corresponds to variant rs12491947 [ dbSNP | Ensembl ].		VAR_059249
	Natural variant	117	1	Y → S in a colorectal cancer sample; somatic mutation. Ref.9		VAR_036081
	Natural variant	206	1	R → C. Ref.8 Corresponds to variant rs35677470 [ dbSNP | Ensembl ].		VAR_061137

Sequences

	Sequence		Length	Mass (Da)
	Q13609 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: BAB9F1A0341E6048	FASTA	305	35,504
	10 20 30 40 50 60 MSRELAPLLL LLLSIHSALA MRICSFNVRS FGESKQEDKN AMDVIVKVIK RCDIILVMEI 70 80 90 100 110 120 KDSNNRICPI LMEKLNRNSR RGITYNYVIS SRLGRNTYKE QYAFLYKEKL VSVKRSYHYH 130 140 150 160 170 180 DYQDGDADVF SREPFVVWFQ SPHTAVKDFV IIPLHTTPET SVKEIDELVE VYTDVKHRWK 190 200 210 220 230 240 AENFIFMGDF NAGCSYVPKK AWKNIRLRTD PRFVWLIGDQ EDTTVKKSTN CAYDRIVLRG 250 260 270 280 290 300 QEIVSSVVPK SNSVFDFQKA YKLTEEEALD VSDHFPVEFK LQSSRAFTNS KKSVTLRKKT KSKRS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification, localization, and expression of two novel human genes similar to deoxyribonuclease I." Rodriguez A.M., Rodin D., Nomura H., Morton C.C., Weremowicz S., Schneider M.C. Genomics 42:507-513(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning and characterization of a novel human DNase." Zeng Z., Parmelee D., Hyaw H., Coleman T.A., Su K., Zhang J., Gentz R., Ruben S., Rosen C., Li Y. Biochem. Biophys. Res. Commun. 231:499-504(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Cloning and characterization of an actin-resistant DNase I-like endonuclease secreted by macrophages." Baron W.F., Pan C.Q., Spencer S.A., Ryan A.M., Lazarus R.A., Baker K.P. Gene 215:291-301(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"cDNA cloning of human DNase gamma: chromosomal localization of its gene and enzymatic properties of recombinant protein." Shiokawa D., Hirai M., Tanuma S. Apoptosis 3:89-95(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT LYS-96. Tissue: Spleen.
[5]	"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]. Tissue: Spleen.
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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: Liver.
[8]	"Loss-of-function variant in DNASE1L3 causes a familial form of systemic lupus erythematosus." Al-Mayouf S.M., Sunker A., Abdwani R., Abrawi S.A., Almurshedi F., Alhashmi N., Al Sonbul A., Sewairi W., Qari A., Abdallah E., Al-Owain M., Al Motywee S., Al-Rayes H., Hashem M., Khalak H., Al-Jebali L., Alkuraya F.S. Nat. Genet. 43:1186-1188(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SLEB16, VARIANT CYS-206.
[9]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-19; ARG-82 AND SER-117.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U56814 mRNA. Translation: AAB63967.1. AF047354 mRNA. Translation: AAC35752.1. U75744 mRNA. Translation: AAC23652.1. AK313303 mRNA. Translation: BAG36108.1. CH471055 Genomic DNA. Translation: EAW65358.1. BC015831 mRNA. Translation: AAH15831.1.
IPI	IPI00014286.
PIR	JC5361.
RefSeq	NP_004935.1. NM_004944.3.
UniGene	Hs.476453.
3D structure databases
ProteinModelPortal	Q13609.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000316193.
PTM databases
PhosphoSite	Q13609.
Polymorphism databases
DMDM	2494173.
Proteomic databases
PaxDb	Q13609.
PRIDE	Q13609.
Protocols and materials databases
DNASU	1776.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000318316; ENSP00000316193; ENSG00000163687. ENST00000394549; ENSP00000378053; ENSG00000163687.
GeneID	1776.
KEGG	hsa:1776.
UCSC	uc003djo.1. human.
Organism-specific databases
CTD	1776.
GeneCards	GC03M058153.
HGNC	HGNC:2959. DNASE1L3.
HPA	HPA019955.
MIM	602244. gene. 614420. phenotype.
neXtProt	NX_Q13609.
Orphanet	300345. Autosomal recessive systemic lupus erythematosus. 93552. Pediatric systemic lupus erythematosus.
PharmGKB	PA27430.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG46375.
HOGENOM	HOG000059570.
HOVERGEN	HBG051368.
InParanoid	Q13609.
KO	K11995.
OMA	AENFIFM.
PhylomeDB	Q13609.
Gene expression databases
ArrayExpress	Q13609.
Bgee	Q13609.
CleanEx	HS_DNASE1L3.
Genevestigator	Q13609.
GermOnline	ENSG00000163687. Homo sapiens.
Family and domain databases
InterPro	IPR018057. Deoxyribonuclease-1_AS. IPR016202. DNase_I-like. IPR008185. DNase_I_euk. IPR005135. Endo/exonuclease/phosphatase. [Graphical view]
PANTHER	PTHR11371. PTHR11371. 1 hit.
Pfam	PF03372. Exo_endo_phos. 1 hit. [Graphical view]
PIRSF	PIRSF000988. DNase_I_euk. 1 hit.
PRINTS	PR00130. DNASEI.
SMART	SM00476. DNaseIc. 1 hit. [Graphical view]
SUPFAM	SSF56219. Exo_endo_phos. 1 hit.
PROSITE	PS00919. DNASE_I_1. 1 hit. PS00918. DNASE_I_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q13609.
ChEMBL	CHEMBL1649048.
GenomeRNAi	1776.
NextBio	7231.
SOURCE	Search...

Entry information

Entry name

DNSL3_HUMAN

Accession

Primary (citable) accession number: Q13609
Secondary accession number(s): B2R8B1, O75803

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 125 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.