DJ-1

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	OMIM: 602533 MGI: 2135637 HomoloGene: 38295 GeneCards: PARK7
Gene location (Human)
Chr.	Chromosome 1 (human)[1]
End	7,985,505 bp[1]
Gene location (Mouse)
Chr.	Chromosome 4 (mouse)[2]
End	150,998,894 bp[2]
RNA expression pattern
	Top expressed in
	tibia; ; deltoid muscle; ; endothelial cell; ; tibialis anterior muscle; ; islet of Langerhans; ; vastus lateralis muscle; ; right ventricle; ; right adrenal gland; ; ganglionic eminence; ; optic nerve;
	Top expressed in
	triceps brachii muscle; ; vastus lateralis muscle; ; gastrocnemius muscle; ; facial motor nucleus; ; tibialis anterior muscle; ; retinal pigment epithelium; ; Paneth cell; ; temporal muscle; ; extensor digitorum longus muscle; ; primitive streak;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	signaling receptor binding; cytokine 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; protein-containing complex binding;
Cellular component	cytoplasm; cytosol; membrane; mitochondrial intermembrane space; mitochondrion; neuron projection; 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; 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 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; 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; 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 by RNA polymerase II; 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

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 functioning 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. DJ-1 is expressed in both the neural retina and retinal pigment epithelium of mammals, where it exerts a neuroprotective role against oxidative stress under both physiological and pathological conditions.[12][13]

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.[14]

Functional DJ-1 protein has been shown to bind metals and protect against metal-induced cytotoxicity from copper and mercury.[15]

DJ-1/PARK7 and its bacterial homologs: Hsp31, YhbO, and YajL can repair methylglyoxal and glyoxal glycated nucleotides.[16] Guanine, either in the form of a free nucleotide or as a nucleotide incorporated into nucleic acid (DNA or RNA), if glycated, can be repaired by DJ-1/PARK7.[16] Deglycase-deficient bacterial mutants with reduced ability to repair glycated bases in DNA show strong mutator phenotypes.[16]

Clinical significance

Defects in this gene are the cause of autosomal recessive early-onset Parkinson's disease 7.[5][17]

Interactions

PARK7 has been shown to interact with:

References

GRCh38: Ensembl release 89: ENSG00000116288 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000028964 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"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.
Martín-Nieto J, Uribe ML, Esteve-Rudd J, Herrero MT, Campello L (August 2019). "A role for DJ-1 against oxidative stress in the mammalian retina". Neurosci Lett. 708: 134361. doi:10.1016/j.neulet.2019.134361. hdl:10045/94474. PMID 31276729. S2CID 195813073.}
Shadrach KG, Rayborn ME, Hollyfield JG, Bonilha VL (2013). "DJ-1-dependent regulation of oxidative stress in the retinal pigment epithelium (RPE)". PLoS One. 8 (7): e67983. Bibcode:2013PLoSO...867983S. doi:10.1371/journal.pone.0067983. PMC 3699467. PMID 23844142.}
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. hdl:2115/53726. 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.
Richarme G, Liu C, Mihoub M, Abdallah J, Leger T, Joly N, Liebart JC, Jurkunas UV, Nadal M, Bouloc P, Dairou J, Lamouri A (July 2017). "Guanine glycation repair by DJ-1/Park7 and its bacterial homologs". Science. 357 (6347): 208–211. doi:10.1126/science.aag1095. PMID 28596309.
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. Bibcode:2003Sci...299..256B. doi:10.1126/science.1077209. PMID 12446870. S2CID 27186691.
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.

External links

Overview of all the structural information available in the PDB for UniProt: Q99497 (Protein/nucleic acid deglycase DJ-1) at the PDBe-KB.

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

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000116288 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000028964 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: PARK7".

[6] "Uniprot: Q99497 - PARK7_HUMAN".

[7] 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.

[8] 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.

[9] 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.

[10] 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.

[11] 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.

[pmid31276729-12] Martín-Nieto J, Uribe ML, Esteve-Rudd J, Herrero MT, Campello L (August 2019). "A role for DJ-1 against oxidative stress in the mammalian retina". Neurosci Lett. 708: 134361. doi:10.1016/j.neulet.2019.134361. hdl:10045/94474. PMID 31276729. S2CID 195813073.}

[pmid23844142-13] Shadrach KG, Rayborn ME, Hollyfield JG, Bonilha VL (2013). "DJ-1-dependent regulation of oxidative stress in the retinal pigment epithelium (RPE)". PLoS One. 8 (7): e67983. Bibcode:2013PLoSO...867983S. doi:10.1371/journal.pone.0067983. PMC 3699467. PMID 23844142.}

[14] 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. hdl:2115/53726. PMID 18591768.

[pmid23792957-15] 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.

[Richarme2017-16] Richarme G, Liu C, Mihoub M, Abdallah J, Leger T, Joly N, Liebart JC, Jurkunas UV, Nadal M, Bouloc P, Dairou J, Lamouri A (July 2017). "Guanine glycation repair by DJ-1/Park7 and its bacterial homologs". Science. 357 (6347): 208–211. doi:10.1126/science.aag1095. PMID 28596309.

[pmid_12446870-17] 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. Bibcode:2003Sci...299..256B. doi:10.1126/science.1077209. PMID 12446870. S2CID 27186691.

[pmid25071438-18] 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.

[pmid12612053-19] 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.

[pmid11477070-20] 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.