PARK7

Parkinson protein 7
PDB rendering based on 1j42 [1].
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​
Identifiers
Symbols	PARK7 ; DJ-1; DJ1; HEL-S-67p
External IDs	OMIM: 602533 MGI: 2135637 HomoloGene: 38295 GeneCards: PARK7 Gene
Gene ontology Molecular function • core promoter binding • double-stranded DNA binding • single-stranded DNA binding • transcription coactivator activity • mRNA binding • receptor binding • copper ion binding • protein binding • transcription factor binding • peptidase activity • superoxide dismutase copper chaperone activity • oxidoreductase activity, acting on peroxide as acceptor • glyoxalase III activity • enzyme binding • kinase binding • cytokine binding • tyrosine 3-monooxygenase activator activity • L-dopa decarboxylase activator activity • identical protein binding • protein homodimerization activity • small protein activating enzyme binding • ubiquitin-like protein conjugating enzyme binding • mercury ion binding • androgen receptor binding • peroxiredoxin activity • repressing transcription factor binding • scaffold protein binding • cupric ion binding • cuprous ion binding • ubiquitin-specific protease binding • glyoxalase (glycolic acid-forming) activity Cellular component • chromatin • nucleus • cytoplasm • mitochondrion • mitochondrial respiratory chain complex I • mitochondrial intermembrane space • mitochondrial matrix • endoplasmic reticulum • cytosol • plasma membrane • PML body • axon • cell body • membrane raft • extracellular exosome Biological process • negative regulation of protein phosphorylation • negative regulation of protein kinase activity • proteolysis • protein deglycosylation • autophagy • inflammatory response • mitochondrion organization • Ras protein signal transduction • single fertilization • adult locomotory behavior • detoxification of copper ion • positive regulation of gene expression • negative regulation of gene expression • enzyme active site formation via L-cysteine sulfinic acid • methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione • lactate biosynthetic process • negative regulation of protein ubiquitination • negative regulation of protein binding • activation of protein kinase B activity • negative regulation of proteasomal ubiquitin-dependent protein catabolic process • positive regulation of interleukin-8 production • positive regulation of peptidyl-serine phosphorylation • negative regulation of protein sumoylation • cellular response to oxidative stress • cellular response to glyoxal • hydrogen peroxide metabolic process • negative regulation of apoptotic process • regulation of neuron apoptotic process • negative regulation of neuron apoptotic process • regulation of TRAIL receptor biosynthetic process • positive regulation of transcription from RNA polymerase II promoter • glycolate biosynthetic process • negative regulation of protein export from nucleus • regulation of inflammatory response • detoxification of mercury ion • protein stabilization • positive regulation of sequence-specific DNA binding transcription factor activity • negative regulation of ubiquitin-protein transferase activity • dopamine uptake involved in synaptic transmission • regulation of mitochondrial membrane potential • positive regulation of protein kinase B signaling • membrane depolarization • membrane hyperpolarization • negative regulation of cell death • regulation of androgen receptor signaling pathway • cellular response to hydrogen peroxide • positive regulation of protein homodimerization activity • positive regulation of protein localization to nucleus • negative regulation of neuron death • positive regulation of superoxide dismutase activity • negative regulation of protein acetylation • positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway • negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway • regulation of fibril organization • positive regulation of mitochondrial electron transport, NADH to ubiquinone • negative regulation of death-inducing signaling complex assembly • negative regulation of protein K48-linked deubiquitination • negative regulation of TRAIL-activated apoptotic signaling pathway • positive regulation of pyrroline-5-carboxylate reductase activity • positive regulation of tyrosine 3-monooxygenase activity • positive regulation of dopamine biosynthetic process • glyoxal catabolic process • positive regulation of L-dopa biosynthetic process • positive regulation of L-dopa decarboxylase activity • negative regulation of oxidative stress-induced cell death • negative regulation of hydrogen peroxide-induced cell death • negative regulation of hydrogen peroxide-induced neuron death • negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway • negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway • positive regulation of reactive oxygen species biosynthetic process • positive regulation of mitophagy • negative regulation of ubiquitin-specific protease activity • positive regulation of oxidative phosphorylation uncoupler activity • positive regulation of transcription regulatory region DNA binding • positive regulation of androgen receptor activity • negative regulation of extrinsic apoptotic signaling pathway • negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	11315	57320
Ensembl	ENSG00000116288	ENSMUSG00000028964
UniProt	Q99497	Q99LX0
RefSeq (mRNA)	NM_001123377	NM_020569
RefSeq (protein)	NP_001116849	NP_065594
Location (UCSC)	Chr 1: 7.95 – 7.99 Mb	Chr 4: 150.9 – 150.91 Mb
PubMed search

Protein deglycase DJ-1, also known as Parkinson disease protein 7, is a protein which in humans is encoded by the PARK7 gene.^[2]

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.^[2]

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.^[3][4][5] It belongs to the peptidase C56 family of proteins.

The protein structures of human protein DJ-1, Escherichia coli chaperone Hsp31 and an Archaea protease are evolutionarily conserved.^[6]

Function

Under an oxidative condition, protein deglycase DJ-1 inhibits the aggregation of α-synuclein via its chaperone activity,^[7][8] 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.^[2] 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.^[9]

Clinical significance

Defects in this gene are the cause of autosomal recessive early-onset Parkinson's disease 7.^[2][10]

Interactions

PARK7 has been shown to interact with:

• CASK,^[11]
• EFCAB6,^[12] and
• PIAS2.^[13]

See also

• Parkinson's disease

References

1. Lee, S. J.; Kim, S. J.; Kim, I. K.; Ko, J.; Jeong, C. S.; Kim, G. H.; Park, C.; Kang, S. O.; Suh, P. G. (2003). "Crystal Structures of Human DJ-1 and Escherichia coli Hsp31, Which Share an Evolutionarily Conserved Domain". Journal of Biological Chemistry 278 (45): 44552–44559. doi:10.1074/jbc.M304517200. PMID 12939276.
2. "Entrez Gene: PARK7".
3. "Uniprot: Q99497 - PARK7_HUMAN".
4. 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.
5. 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.
6. 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.
7. 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. PMID 15502874.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.

Further reading

• 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.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.