Q99LX0 (PARK7_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein DJ-1
EC=3.4.-.-

Alternative name(s):
Parkinson disease protein 7 homolog

Gene names

Name:

Park7

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	189 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	Protects cells against oxidative stress and cell death. Plays a role in regulating expression or stability of the mitochondrial uncoupling proteins SLC25A14 and SLC25A27 in dopaminergic neurons of the substantia nigra pars compacta and attenuates the oxidative stress induced by calcium entry into the neurons via L-type channels during pacemaking. Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death. May act as an atypical peroxiredoxin-like peroxidase that scavenges hydrogen peroxide. Following removal of a C-terminal peptide, displays protease activity and enhanced cytoprotective action against oxidative stress-induced apoptosis. Stabilizes NFE2L2 by preventing its association with KEAP1 and its subsequent ubiquitination. Binds to OTUD7B and inhibits its deubiquitinating activity. Enhances RELA nuclear translocation. Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress. Required for correct mitochondrial morphology and function and for autophagy of dysfunctional mitochondria. Regulates astrocyte inflammatory responses. Acts as a positive regulator of androgen receptor-dependent transcription. Prevents aggregation of SNCA. Plays a role in fertilization. Has no proteolytic activity. Has cell-growth promoting activity and transforming activity. May function as a redox-sensitive chaperone. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14
Subunit structure	Homodimer. Binds EFCAB6/DJBP and PIAS2. Part of a ternary complex containing PARK7, EFCAB6/DJBP and AR By similarity. Interacts (via N-terminus) with OTUD7B. Interacts with BBS1, CLCF1 and MTERF. Binds to HIPK1 By similarity. Ref.12
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Mitochondrion By similarity. Note: Under normal conditions, located predominantly in the cytoplasm and, to a lesser extent, in the nucleus and mitochondrion. Translocates to the mitochondrion and subsequently to the nucleus in response to oxidative stress and exerts an increased cytoprotective effect against oxidative damage By similarity.
Tissue specificity	Expressed in erythroblasts and in mature red blood cells from peripheral blood (at protein level). Ref.11
Developmental stage	Expression increases during erythroid development (at protein level). Ref.11
Induction	By hydrogen peroxide. Ref.6
Post-translational modification	Sumoylated on Lys-130 by PIAS2 or PIAS4; which is essential for cell-growth promoting activity and transforming activity By similarity. Undergoes cleavage of a C-terminal peptide and subsequent activation of protease activity in response to oxidative stress By similarity.
Disruption phenotype	Increased sensitivity of embryonic cortical neurons to oxidative stress. Age-dependent increase in mitochondrial hydrogen peroxide production and reduced mitochondrial aconitase activity. Down-regulation of Slc25a14 and Slc25a27, compromised calcium-induced uncoupling and increased oxidation of mitochondrial matrix proteins specifically in the dopaminergic neurons of the substantia nigra pars compacta. Reduced N2el2 protein expression. Impaired mitochondrial function and morphology with reduced autophagy leading to accumulation of defective mitochondria. Ref.7 Ref.8 Ref.9 Ref.13 Ref.14
Sequence similarities	Belongs to the peptidase C56 family.

Ontologies

Keywords
Biological process	Autophagy Fertilization Inflammatory response Stress response
Cellular component	Cytoplasm Mitochondrion Nucleus
Disease	Tumor suppressor
Ligand	RNA-binding
Molecular function	Chaperone Hydrolase Protease
PTM	Isopeptide bond Oxidation Phosphoprotein Ubl conjugation Zymogen
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	adult locomotory behavior Inferred from mutant phenotype PubMed 15721235PubMed 15799973. Source: MGI autophagy Inferred from electronic annotation. Source: UniProtKB-KW cell proliferation Traceable author statement Ref.1. Source: MGI cellular response to hydrogen peroxide Inferred from mutant phenotype Ref.7. Source: UniProtKB dopamine uptake involved in synaptic transmission Inferred from mutant phenotype PubMed 15721235. Source: MGI hydrogen peroxide metabolic process Inferred from mutant phenotype Ref.9. Source: MGI inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW membrane depolarization Inferred from mutant phenotype PubMed 16624565. Source: MGI membrane hyperpolarization Inferred from mutant phenotype PubMed 16624565. Source: MGI mitochondrion organization Inferred from mutant phenotype Ref.14. Source: UniProtKB negative regulation of cell death Inferred from mutant phenotype Ref.7. Source: UniProtKB negative regulation of extrinsic apoptotic signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of protein binding Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of oxidative phosphorylation uncoupler activity Inferred from mutant phenotype Ref.13. Source: UniProtKB protein stabilization Inferred from mutant phenotype Ref.8. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: UniProtKB-KW regulation of androgen receptor signaling pathway Inferred from electronic annotation. Source: Compara regulation of inflammatory response Inferred from mutant phenotype Ref.10. Source: UniProtKB regulation of neuron apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB single fertilization Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	mitochondrion Inferred from direct assay Ref.9PubMed 18614015. Source: MGI nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	mRNA binding Inferred from sequence or structural similarity. Source: UniProtKB peptidase activity Inferred from sequence or structural similarity. Source: UniProtKB peroxidase activity Inferred from mutant phenotype Ref.9. Source: UniProtKB peroxiredoxin activity Inferred from mutant phenotype Ref.9. Source: MGI protein homodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – ?		Protein DJ-1		PRO_0000157850
	Propeptide	? – 189		Removed in mature form By similarity		PRO_0000405560
Sites
	Active site	106	1	By similarity
	Active site	126	1	By similarity
Amino acid modifications
	Modified residue	67	1	Phosphotyrosine By similarity
	Modified residue	106	1	Cysteine sulfinic acid (-SO2H) By similarity
	Cross-link	130		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Experimental info
	Mutagenesis	46	1	C → A: Sulfinic acid detected following treatment with hydrogen peroxide. Ref.9
	Mutagenesis	53	1	C → A: Sulfinic acid detected following treatment with hydrogen peroxide. Ref.9
	Mutagenesis	106	1	C → A: No sulfinic acid detected following treatment with hydrogen peroxide. Ref.9
	Sequence conflict	127	1	P → T in BAE40278. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q99LX0 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 877C825CCA07468F	FASTA	189	20,021
	10 20 30 40 50 60 MASKRALVIL AKGAEEMETV IPVDVMRRAG IKVTVAGLAG KDPVQCSRDV MICPDTSLED 70 80 90 100 110 120 AKTQGPYDVV VLPGGNLGAQ NLSESPMVKE ILKEQESRKG LIAAICAGPT ALLAHEVGFG 130 140 150 160 170 180 CKVTTHPLAK DKMMNGSHYS YSESRVEKDG LILTSRGPGT SFEFALAIVE ALVGKDMANQ VKAPLVLKD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of human and mouse DJ-1 genes and identification of Sp1-dependent activation of the human DJ-1 promoter." Taira T., Takahashi K., Kitagawa R., Iguchi-Ariga S.M.M., Ariga H. Gene 263:285-292(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: BALB/c and NOD. Tissue: Thymus.
[3]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[4]	"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]. Strain: FVB/N. Tissue: Mammary tumor.
[5]	Lubec G., Klug S. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 13-27; 63-89 AND 99-122, MASS SPECTROMETRY. Tissue: Hippocampus.
[6]	"DJ-1 has a role in antioxidative stress to prevent cell death." Taira T., Saito Y., Niki T., Iguchi-Ariga S.M., Takahashi K., Ariga H. EMBO Rep. 5:213-218(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[7]	"Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress." Kim R.H., Smith P.D., Aleyasin H., Hayley S., Mount M.P., Pownall S., Wakeham A., You-Ten A.J., Kalia S.K., Horne P., Westaway D., Lozano A.M., Anisman H., Park D.S., Mak T.W. Proc. Natl. Acad. Sci. U.S.A. 102:5215-5220(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[8]	"DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2." Clements C.M., McNally R.S., Conti B.J., Mak T.W., Ting J.P. Proc. Natl. Acad. Sci. U.S.A. 103:15091-15096(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[9]	"DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase." Andres-Mateos E., Perier C., Zhang L., Blanchard-Fillion B., Greco T.M., Thomas B., Ko H.S., Sasaki M., Ischiropoulos H., Przedborski S., Dawson T.M., Dawson V.L. Proc. Natl. Acad. Sci. U.S.A. 104:14807-14812(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE, MUTAGENESIS OF CYS-46; CYS-53 AND CYS-106.
[10]	"Regulation of astrocyte inflammatory responses by the Parkinson's disease-associated gene DJ-1." Waak J., Weber S.S., Waldenmaier A., Gorner K., Alunni-Fabbroni M., Schell H., Vogt-Weisenhorn D., Pham T.T., Reumers V., Baekelandt V., Wurst W., Kahle P.J. FASEB J. 23:2478-2489(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"The familial Parkinson's disease gene DJ-1 (PARK7) is expressed in red cells and plays a role in protection against oxidative damage." Xu X., Martin F., Friedman J.S. Blood Cells Mol. Dis. 45:227-232(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[12]	"DJ-1 enhances cell survival through the binding of cezanne, a negative regulator of NF-{kappa}B." McNally R.S., Davis B.K., Clements C.M., Accavitti-Loper M.A., Mak T.W., Ting J.P. J. Biol. Chem. 286:4098-4106(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BBS1; CLCF1; MTERF AND OTUD7B.
[13]	"Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1." Guzman J.N., Sanchez-Padilla J., Wokosin D., Kondapalli J., Ilijic E., Schumacker P.T., Surmeier D.J. Nature 468:696-700(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[14]	"Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson's disease-associated protein DJ-1." Krebiehl G., Ruckerbauer S., Burbulla L.F., Kieper N., Maurer B., Waak J., Wolburg H., Gizatullina Z., Gellerich F.N., Woitalla D., Riess O., Kahle P.J., Proikas-Cezanne T., Kruger R. PLoS ONE 5:E9367-E9367(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB015652 mRNA. Translation: BAA29063.2. AK146368 mRNA. Translation: BAE27118.1. AK153948 mRNA. Translation: BAE32271.1. AK168341 mRNA. Translation: BAE40278.1. AL607084 Genomic DNA. Translation: CAM19230.1. BC002187 mRNA. Translation: AAH02187.1.
IPI	IPI00117264.
RefSeq	NP_065594.2. NM_020569.3.
UniGene	Mm.277349.
3D structure databases
ProteinModelPortal	Q99LX0.
SMR	Q99LX0. Positions 1-189.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99LX0. 2 interactions.
MINT	MINT-1869265.
STRING	10090.ENSMUSP00000101300.
Protein family/group databases
MEROPS	C56.002.
PTM databases
PhosphoSite	Q99LX0.
2D gel databases
REPRODUCTION-2DPAGE	Q99LX0.
UCD-2DPAGE	Q99LX0.
Proteomic databases
PaxDb	Q99LX0.
PRIDE	Q99LX0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000030805; ENSMUSP00000030805; ENSMUSG00000028964. ENSMUST00000105673; ENSMUSP00000101298; ENSMUSG00000028964. ENSMUST00000105674; ENSMUSP00000101299; ENSMUSG00000028964. ENSMUST00000105675; ENSMUSP00000101300; ENSMUSG00000028964.
GeneID	57320.
KEGG	mmu:57320.
UCSC	uc008vxz.2. mouse.
Organism-specific databases
CTD	11315.
MGI	MGI:2135637. Park7.
Phylogenomic databases
eggNOG	COG0693.
GeneTree	ENSGT00390000001231.
HOGENOM	HOG000063194.
HOVERGEN	HBG053511.
InParanoid	Q99LX0.
KO	K05687.
OMA	GDHYKYS.
OrthoDB	EOG4DJJXJ.
Gene expression databases
ArrayExpress	Q99LX0.
Bgee	Q99LX0.
Genevestigator	Q99LX0.
GermOnline	ENSMUSG00000028964. Mus musculus.
Family and domain databases
InterPro	IPR006287. DJ1. IPR002818. ThiJ/PfpI. [Graphical view]
Pfam	PF01965. DJ-1_PfpI. 1 hit. [Graphical view]
TIGRFAMs	TIGR01383. not_thiJ. 1 hit.
ProtoNet	Search...
Other
NextBio	313682.
SOURCE	Search...

Entry information

Entry name

PARK7_MOUSE

Accession

Primary (citable) accession number: Q99LX0
Secondary accession number(s): O88306, Q3THB9, Q3U509

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 7, 2004
Last sequence update:	June 1, 2001
Last modified:	May 29, 2013
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program