Ttyjfyk

PARK7
Available structures
PDB	Ortholog search: PDBe RCSB ;
List of PDB id codes
	1J42, 1P5F, 1PDV, 1PDW, 1PE0, 1Q2U, 1SOA, 1UCF, 2OR3, 2R1T, 2R1U, 2R1V, 2RK3, 2RK4, 2RK6, 3B36, 3B38, 3B3A, 3BWE, 3CY6, 3CYF, 3CZ9, 3CZA, 3EZG, 3F71, 3SF8, 4BTE, 4MNT, 4MTC, 4N0M, 4N12, 4OGF, 4OQ4, 4P2G, 4P34, 4P35, 4P36, 4ZGG, 4RKW, 4RKY, 4S0Z
Identifiers
Aliases	; PARK7, DJ-1, DJ1, HEL-S-67p, Parkinsonism associated deglycase, GATD2
External IDs	MGI: 2135637 HomoloGene: 38295 GeneCards: PARK7
Gene location (Human)
Chr.	Chromosome 1 (human)
	; ; ;
End	7,985,505 bp
Gene location (Mouse)
Chr.	Chromosome 4 (mouse)
	; ; ;
End	150,914,437 bp
; RNA expression pattern
	More reference expression data
Gene ontology
Molecular function	• receptor binding; • repressing transcription factor binding; • cytokine binding; • core promoter binding; • cupric ion binding; • transcription factor binding; • L-dopa decarboxylase activator activity; • peptidase activity; • kinase binding; • tyrosine 3-monooxygenase activator activity; • enzyme binding; • mRNA binding; • protein homodimerization activity; • scaffold protein binding; • small protein activating enzyme binding; • single-stranded DNA binding; • ubiquitin-like protein conjugating enzyme binding; • protein binding; • peroxiredoxin activity; • double-stranded DNA binding; • copper ion binding; • mercury ion binding; • transcription coactivator activity; • oxidoreductase activity, acting on peroxide as acceptor; • androgen receptor binding; • superoxide dismutase copper chaperone activity; • RNA binding; • identical protein binding; • ubiquitin-specific protease binding; • hydrolase activity; • cuprous ion binding; • cadherin binding; • protein deglycase activity;
Cellular component	• cytoplasm; • cytosol; • membrane; • mitochondrial intermembrane space; • mitochondrion; • neuron projection; • cell nucleus; • mitochondrial respiratory chain complex I; • endoplasmic reticulum; • membrane raft; • chromatin; • extracellular exosome; • plasma membrane; • mitochondrial matrix; • cell body; • PML body; • presynapse; • perinuclear region of cytoplasm; • cell-cell adherens junction; • axon; • nucleoplasm;
Biological process	• negative regulation of neuron apoptotic process; • positive regulation of transcription regulatory region DNA binding; • negative regulation of protein sumoylation; • negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; • negative regulation of protein binding; • synaptic transmission, dopaminergic; • positive regulation of interleukin-8 production; • negative regulation of proteasomal ubiquitin-dependent protein catabolic process; • Ras protein signal transduction; • cellular response to glyoxal; • negative regulation of protein acetylation; • positive regulation of reactive oxygen species biosynthetic process; • positive regulation of oxidative phosphorylation uncoupler activity; • positive regulation of protein kinase B signaling; • negative regulation of protein catabolic process; • adult locomotory behavior; • regulation of neuron apoptotic process; • negative regulation of extrinsic apoptotic signaling pathway; • negative regulation of cell death; • glycolate biosynthetic process; • positive regulation of protein homodimerization activity; • negative regulation of gene expression; • single fertilization; • positive regulation of peptidyl-serine phosphorylation; • positive regulation of mitochondrial electron transport, NADH to ubiquinone; • negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway; • negative regulation of oxidative stress-induced cell death; • inflammatory response; • negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; • regulation of supramolecular fiber organization; • negative regulation of neuron death; • negative regulation of protein phosphorylation; • negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; • negative regulation of protein kinase activity; • negative regulation of oxidative stress-induced neuron death; • membrane depolarization; • protein stabilization; • mitochondrion organization; • positive regulation of sequence-specific DNA binding transcription factor activity; • negative regulation of death-inducing signaling complex assembly; • negative regulation of apoptotic process; • proteolysis; • negative regulation of protein K48-linked deubiquitination; • enzyme active site formation via L-cysteine sulfinic acid; • dopamine uptake involved in synaptic transmission; • positive regulation of tyrosine 3-monooxygenase activity; • positive regulation of L-dopa decarboxylase activity; • negative regulation of hydrogen peroxide-induced neuron death; • regulation of inflammatory response; • regulation of androgen receptor signaling pathway; • negative regulation of hydrogen peroxide-induced cell death; • positive regulation of autophagy of mitochondrion; • response to hydrogen peroxide; • detoxification of copper ion; • positive regulation of superoxide dismutase activity; • positive regulation of dopamine biosynthetic process; • positive regulation of protein localization to nucleus; • positive regulation of L-dopa biosynthetic process; • activation of protein kinase B activity; • membrane hyperpolarization; • detoxification of mercury ion; • negative regulation of TRAIL-activated apoptotic signaling pathway; • cellular oxidant detoxification; • negative regulation of ubiquitin-specific protease activity; • regulation of TRAIL receptor biosynthetic process; • autophagy; • cellular response to reactive oxygen species; • regulation of mitochondrial membrane potential; • negative regulation of protein ubiquitination; • hydrogen peroxide metabolic process; • positive regulation of gene expression; • negative regulation of protein export from nucleus; • negative regulation of ubiquitin-protein transferase activity; • positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; • cellular response to oxidative stress; • positive regulation of androgen receptor activity; • positive regulation of pyrroline-5-carboxylate reductase activity; • positive regulation of transcription from RNA polymerase II promoter; • cellular response to hydrogen peroxide; • methylglyoxal metabolic process; • lactate biosynthetic process; • peptidyl-cysteine deglycation; • peptidyl-arginine deglycation; • peptidyl-lysine deglycation; • protein deglycation, glyoxal removal; • protein deglycation, methylglyoxal removal; • glutathione deglycation; • glyoxal metabolic process; • negative regulation of nitrosative stress-induced intrinsic apoptotic signaling pathway; • positive regulation of acute inflammatory response to antigenic stimulus; • protein deglycosylation; • positive regulation of NAD(P)H oxidase activity; • DNA repair; • cellular response to DNA damage stimulus; • insulin secretion; • glucose homeostasis; • guanine deglycation; • guanine deglycation, methylglyoxal removal; • guanine deglycation, glyoxal removal; • negative regulation of reactive oxygen species biosynthetic process;
	Sources:Amigo / QuickGO;
Orthologs
	11315
	57320
	ENSG00000116288
	ENSMUSG00000028964
	Q99497
	Q99LX0
	NM_001123377; NM_007262
	NM_020569
	NP_001116849; NP_009193
	NP_065594
	Wikidata
View/Edit Human	View/Edit Mouse

‹ The template Infobox gene is being considered for merging. ›

Protein deglycase DJ-1, also known as Parkinson disease protein 7, is a protein which in humans is encoded by the PARK7 gene.^[5]

Structure

Gene

The gene PARK7, also known as DJ-1, encodes a protein of the peptidase C56 family. The human gene PARK7 has 8 Exons and locates at chromosome band 1p36.23.^[5]

Protein

The human protein deglycase DJ-1 is 20 kDa in size and composed of 189 amino acids with seven β-strands and nine α-helices in total and is present as a dimer.^[6]^[7]^[8] It belongs to the peptidase C56 family of proteins.

The protein structures of human protein DJ-1, Escherichia coli chaperone Hsp31, YhbO and YajL and an Archaea protease are evolutionarily conserved.^[9]

Function

Under an oxidative condition, protein deglycase DJ-1 inhibits the aggregation of α-synuclein via its chaperone activity,^[10]^[11] thus functions as a redox-sensitive chaperone and as a sensor for oxidative stress. Accordingly, DJ-1 apparently protects neurons against oxidative stress and cell death.^[5] In parallel, Protein DJ-1 acts as a positive regulator of androgen receptor-dependent transcription.

Pyrroloquinoline quinone (PQQ) has been shown to reduce the self-oxidation of the DJ-1 protein, an early step in the onset of some forms of Parkinson's disease.^[12]

Functional DJ-1 protein has been shown to bind metals and protect against metal-induced cytotoxicity from copper and mercury.^[13]

Clinical significance

Defects in this gene are the cause of autosomal recessive early-onset Parkinson's disease 7.^[5]^[14]

Interactions

PARK7 has been shown to interact with:

CASK,^[15]

EFCAB6,^[16] and

PIAS2.^[17]

References

^ ^a^b^c GRCh38: Ensembl release 89: ENSG00000116288 - Ensembl, May 2017

^ ^a^b^c GRCm38: Ensembl release 89: ENSMUSG00000028964 - Ensembl, May 2017

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^ "Mouse PubMed Reference:".

^ ^a^b^c^d "Entrez Gene: PARK7".

^ "Uniprot: Q99497 - PARK7_HUMAN".

^ Honbou K, Suzuki NN, Horiuchi M, Niki T, Taira T, Ariga H, Inagaki F (Aug 2003). "The crystal structure of DJ-1, a protein related to male fertility and Parkinson's disease". The Journal of Biological Chemistry. 278 (33): 31380–4. doi:10.1074/jbc.M305878200. PMID 12796482.

^ Tao X, Tong L (Aug 2003). "Crystal structure of human DJ-1, a protein associated with early onset Parkinson's disease". The Journal of Biological Chemistry. 278 (33): 31372–9. doi:10.1074/jbc.M304221200. PMID 12761214.

^ Lee SJ, Kim SJ, Kim IK, Ko J, Jeong CS, Kim GH, Park C, Kang SO, Suh PG, Lee HS, Cha SS (Nov 2003). "Crystal structures of human DJ-1 and Escherichia coli Hsp31, which share an evolutionarily conserved domain". The Journal of Biological Chemistry. 278 (45): 44552–9. doi:10.1074/jbc.M304517200. PMID 12939276.

^ Shendelman S, Jonason A, Martinat C, Leete T, Abeliovich A (Nov 2004). "DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation". PLoS Biology. 2 (11): e362. doi:10.1371/journal.pbio.0020362. PMC 521177. PMID 15502874.

^ Zhou W, Zhu M, Wilson MA, Petsko GA, Fink AL (Mar 2006). "The oxidation state of DJ-1 regulates its chaperone activity toward alpha-synuclein". Journal of Molecular Biology. 356 (4): 1036–48. doi:10.1016/j.jmb.2005.12.030. PMID 16403519.

^ Nunome K, Miyazaki S, Nakano M, Iguchi-Ariga S, Ariga H (Jul 2008). "Pyrroloquinoline quinone prevents oxidative stress-induced neuronal death probably through changes in oxidative status of DJ-1". Biological & Pharmaceutical Bulletin. 31 (7): 1321–6. doi:10.1248/bpb.31.1321. PMID 18591768.

^ Björkblom B, Adilbayeva A, Maple-Grødem J, Piston D, Ökvist M, Xu XM, Brede C, Larsen JP, Møller SG (2013). "Parkinson disease protein DJ-1 binds metals and protects against metal-induced cytotoxicity". Journal of Biological Chemistry. 288 (31): 22809–20. doi:10.1074/jbc.M113.482091. PMC 3829365. PMID 23792957.

^ Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MC, Squitieri F, Ibanez P, Joosse M, van Dongen JW, Vanacore N, van Swieten JC, Brice A, Meco G, van Duijn CM, Oostra BA, Heutink P (Jan 2003). "Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism". Science. 299 (5604): 256–9. doi:10.1126/science.1077209. PMID 12446870.

^ Mukherjee K, Slawson JB, Christmann BL, Griffith LC (2014). "Neuron-specific protein interactions of Drosophila CASK-β are revealed by mass spectrometry". Frontiers in Molecular Neuroscience. 7: 58. doi:10.3389/fnmol.2014.00058. PMC 4075472. PMID 25071438.

^ Niki T, Takahashi-Niki K, Taira T, Iguchi-Ariga SM, Ariga H (Feb 2003). "DJBP: a novel DJ-1-binding protein, negatively regulates the androgen receptor by recruiting histone deacetylase complex, and DJ-1 antagonizes this inhibition by abrogation of this complex". Molecular Cancer Research. 1 (4): 247–61. PMID 12612053.

^ Takahashi K, Taira T, Niki T, Seino C, Iguchi-Ariga SM, Ariga H (Oct 2001). "DJ-1 positively regulates the androgen receptor by impairing the binding of PIASx alpha to the receptor". The Journal of Biological Chemistry. 276 (40): 37556–63. doi:10.1074/jbc.M101730200. PMID 11477070.

.mw-parser-output .refbeginfont-size:90%;margin-bottom:0.5em.mw-parser-output .refbegin-hanging-indents>ullist-style-type:none;margin-left:0.mw-parser-output .refbegin-hanging-indents>ul>li,.mw-parser-output .refbegin-hanging-indents>dl>ddmargin-left:0;padding-left:3.2em;text-indent:-3.2em;list-style:none.mw-parser-output .refbegin-100font-size:100%

Cookson MR (Jan 2003). "Pathways to Parkinsonism". Neuron. 37 (1): 7–10. doi:10.1016/S0896-6273(02)01166-2. PMID 12526767.

Bonifati V, Oostra BA, Heutink P (Mar 2004). "Linking DJ-1 to neurodegeneration offers novel insights for understanding the pathogenesis of Parkinson's disease". Journal of Molecular Medicine. 82 (3): 163–74. doi:10.1007/s00109-003-0512-1. PMID 14712351.

Le W, Appel SH (Feb 2004). "Mutant genes responsible for Parkinson's disease". Current Opinion in Pharmacology. 4 (1): 79–84. doi:10.1016/j.coph.2003.09.005. PMID 15018843.

Abou-Sleiman PM, Healy DG, Wood NW (Oct 2004). "Causes of Parkinson's disease: genetics of DJ-1". Cell and Tissue Research. 318 (1): 185–8. doi:10.1007/s00441-004-0922-6. PMID 15503154.

Pankratz N, Foroud T (Apr 2004). "Genetics of Parkinson disease". NeuroRx. 1 (2): 235–42. doi:10.1602/neurorx.1.2.235. PMC 534935. PMID 15717024.

Heutink P (2006). "PINK-1 and DJ-1--new genes for autosomal recessive Parkinson's disease". Journal of Neural Transmission. Supplementum. Journal of Neural Transmission. Supplementa. 70 (70): 215–9. doi:10.1007/978-3-211-45295-0_33. ISBN 978-3-211-28927-3. PMID 17017532.

Lev N, Roncevic D, Roncevich D, Ickowicz D, Melamed E, Offen D (2007). "Role of DJ-1 in Parkinson's disease". Journal of Molecular Neuroscience. 29 (3): 215–25. doi:10.1385/JMN:29:3:215. PMID 17085780.

Nagakubo D, Taira T, Kitaura H, Ikeda M, Tamai K, Iguchi-Ariga SM, Ariga H (Feb 1997). "DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras". Biochemical and Biophysical Research Communications. 231 (2): 509–13. doi:10.1006/bbrc.1997.6132. PMID 9070310.

Taira T, Takahashi K, Kitagawa R, Iguchi-Ariga SM, Ariga H (Jan 2001). "Molecular cloning of human and mouse DJ-1 genes and identification of Sp1-dependent activation of the human DJ-1 promoter". Gene. 263 (1–2): 285–92. doi:10.1016/S0378-1119(00)00590-4. PMID 11223268.

van Duijn CM, Dekker MC, Bonifati V, Galjaard RJ, Houwing-Duistermaat JJ, Snijders PJ, Testers L, Breedveld GJ, Horstink M, Sandkuijl LA, van Swieten JC, Oostra BA, Heutink P (Sep 2001). "Park7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36". American Journal of Human Genetics. 69 (3): 629–34. doi:10.1086/322996. PMC 1235491. PMID 11462174.

Takahashi K, Taira T, Niki T, Seino C, Iguchi-Ariga SM, Ariga H (Oct 2001). "DJ-1 positively regulates the androgen receptor by impairing the binding of PIASx alpha to the receptor". The Journal of Biological Chemistry. 276 (40): 37556–63. doi:10.1074/jbc.M101730200. PMID 11477070.

Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MC, Squitieri F, Ibanez P, Joosse M, van Dongen JW, Vanacore N, van Swieten JC, Brice A, Meco G, van Duijn CM, Oostra BA, Heutink P (Jan 2003). "Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism". Science. 299 (5604): 256–9. doi:10.1126/science.1077209. PMID 12446870.

Bonifati V, Dekker MC, Vanacore N, Fabbrini G, Squitieri F, Marconi R, Antonini A, Brustenghi P, Dalla Libera A, De Mari M, Stocchi F, Montagna P, Gallai V, Rizzu P, van Swieten JC, Oostra B, van Duijn CM, Meco G, Heutink P (Sep 2002). "Autosomal recessive early onset parkinsonism is linked to three loci: PARK2, PARK6, and PARK7". Neurological Sciences. 23 Suppl 2: S59–60. doi:10.1007/s100720200069. PMID 12548343.

Niki T, Takahashi-Niki K, Taira T, Iguchi-Ariga SM, Ariga H (Feb 2003). "DJBP: a novel DJ-1-binding protein, negatively regulates the androgen receptor by recruiting histone deacetylase complex, and DJ-1 antagonizes this inhibition by abrogation of this complex". Molecular Cancer Research. 1 (4): 247–61. PMID 12612053.

Tao X, Tong L (Aug 2003). "Crystal structure of human DJ-1, a protein associated with early onset Parkinson's disease". The Journal of Biological Chemistry. 278 (33): 31372–9. doi:10.1074/jbc.M304221200. PMID 12761214.

Honbou K, Suzuki NN, Horiuchi M, Niki T, Taira T, Ariga H, Inagaki F (Aug 2003). "The crystal structure of DJ-1, a protein related to male fertility and Parkinson's disease". The Journal of Biological Chemistry. 278 (33): 31380–4. doi:10.1074/jbc.M305878200. PMID 12796482.

Dekker M, Bonifati V, van Swieten J, Leenders N, Galjaard RJ, Snijders P, Horstink M, Heutink P, Oostra B, van Duijn C (Jul 2003). "Clinical features and neuroimaging of PARK7-linked parkinsonism". Movement Disorders. 18 (7): 751–7. doi:10.1002/mds.10422. PMID 12815653.

Miller DW, Ahmad R, Hague S, Baptista MJ, Canet-Aviles R, McLendon C, Carter DM, Zhu PP, Stadler J, Chandran J, Klinefelter GR, Blackstone C, Cookson MR (Sep 2003). "L166P mutant DJ-1, causative for recessive Parkinson's disease, is degraded through the ubiquitin-proteasome system". The Journal of Biological Chemistry. 278 (38): 36588–95. doi:10.1074/jbc.M304272200. PMID 12851414.