“PARK7”的意思、由来-开放百科全书

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.^[1]

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.^[2]^[3]^[4] 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.^[5]

Function

Under an oxidative condition, protein deglycase DJ-1 inhibits the aggregation of α-synuclein via its chaperone activity,^[6]^[7] 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.^[1] In parallel, Protein DJ-1 acts as a positive regulator of androgen receptor-dependent transcription.

Functional DJ-1 protein has been shown to bind metals and protect against metal-induced cytotoxicity from copper and mercury.^[9]

Clinical significance

Defects in this gene are the cause of autosomal recessive early-onset Parkinson's disease 7.^[1]^[10]

Interactions

See also

References

1. ^¹²³{{cite web | title = Entrez Gene: PARK7 | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=11315| accessdate = }}
2. ^{{cite web|title=Uniprot: Q99497 - PARK7_HUMAN|url=https://www.uniprot.org/uniprot/Q99497}}
3. ^{{cite journal | vauthors = Honbou K, Suzuki NN, Horiuchi M, Niki T, Taira T, Ariga H, Inagaki F | title = The crystal structure of DJ-1, a protein related to male fertility and Parkinson's disease | journal = The Journal of Biological Chemistry | volume = 278 | issue = 33 | pages = 31380–4 | date = Aug 2003 | pmid = 12796482 | doi = 10.1074/jbc.M305878200 }}
4. ^{{cite journal | vauthors = Tao X, Tong L | title = Crystal structure of human DJ-1, a protein associated with early onset Parkinson's disease | journal = The Journal of Biological Chemistry | volume = 278 | issue = 33 | pages = 31372–9 | date = Aug 2003 | pmid = 12761214 | doi = 10.1074/jbc.M304221200 }}
5. ^{{cite journal | vauthors = Lee SJ, Kim SJ, Kim IK, Ko J, Jeong CS, Kim GH, Park C, Kang SO, Suh PG, Lee HS, Cha SS | title = Crystal structures of human DJ-1 and Escherichia coli Hsp31, which share an evolutionarily conserved domain | journal = The Journal of Biological Chemistry | volume = 278 | issue = 45 | pages = 44552–9 | date = Nov 2003 | pmid = 12939276 | doi = 10.1074/jbc.M304517200 }}
6. ^{{cite journal | vauthors = Shendelman S, Jonason A, Martinat C, Leete T, Abeliovich A | title = DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation | journal = PLoS Biology | volume = 2 | issue = 11 | pages = e362 | date = Nov 2004 | pmid = 15502874 | doi = 10.1371/journal.pbio.0020362 | pmc=521177}}
7. ^{{cite journal | vauthors = Zhou W, Zhu M, Wilson MA, Petsko GA, Fink AL | title = The oxidation state of DJ-1 regulates its chaperone activity toward alpha-synuclein | journal = Journal of Molecular Biology | volume = 356 | issue = 4 | pages = 1036–48 | date = Mar 2006 | pmid = 16403519 | doi = 10.1016/j.jmb.2005.12.030 }}
8. ^{{cite journal | vauthors = Nunome K, Miyazaki S, Nakano M, Iguchi-Ariga S, Ariga H | title = Pyrroloquinoline quinone prevents oxidative stress-induced neuronal death probably through changes in oxidative status of DJ-1 | journal = Biological & Pharmaceutical Bulletin | volume = 31 | issue = 7 | pages = 1321–6 | date = Jul 2008 | pmid = 18591768 | doi = 10.1248/bpb.31.1321 }}
9. ^{{cite journal | vauthors = Björkblom B, Adilbayeva A, Maple-Grødem J, Piston D, Ökvist M, Xu XM, Brede C, Larsen JP, Møller SG | title = Parkinson disease protein DJ-1 binds metals and protects against metal-induced cytotoxicity. | journal = Journal of Biological Chemistry | year = 2013 | volume = 288 | issue = 31 | pages = 22809-20 | pmid = 23792957 | doi = 10.1074/jbc.M113.482091 | pmc = 3829365 }}
10. ^{{cite journal | vauthors = 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 | title = Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism | journal = Science | volume = 299 | issue = 5604 | pages = 256–9 | date = Jan 2003 | pmid = 12446870 | doi = 10.1126/science.1077209 }}
11. ^{{cite journal | vauthors = Mukherjee K, Slawson JB, Christmann BL, Griffith LC | title = Neuron-specific protein interactions of Drosophila CASK-β are revealed by mass spectrometry | journal = Frontiers in Molecular Neuroscience | volume = 7 | issue = | pages = 58 | year = 2014 | pmid = 25071438 | pmc = 4075472 | doi = 10.3389/fnmol.2014.00058 }}
12. ^{{cite journal | vauthors = Niki T, Takahashi-Niki K, Taira T, Iguchi-Ariga SM, Ariga H | title = 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 | journal = Molecular Cancer Research | volume = 1 | issue = 4 | pages = 247–61 | date = Feb 2003 | pmid = 12612053 | doi = }}
13. ^{{cite journal | vauthors = Takahashi K, Taira T, Niki T, Seino C, Iguchi-Ariga SM, Ariga H | title = DJ-1 positively regulates the androgen receptor by impairing the binding of PIASx alpha to the receptor | journal = The Journal of Biological Chemistry | volume = 276 | issue = 40 | pages = 37556–63 | date = Oct 2001 | pmid = 11477070 | doi = 10.1074/jbc.M101730200 }}

Further reading

{{cite journal | vauthors = Cookson MR | title = Pathways to Parkinsonism | journal = Neuron | volume = 37 | issue = 1 | pages = 7–10 | date = Jan 2003 | pmid = 12526767 | doi = 10.1016/S0896-6273(02)01166-2 }}

{{cite journal | vauthors = Bonifati V, Oostra BA, Heutink P | title = Linking DJ-1 to neurodegeneration offers novel insights for understanding the pathogenesis of Parkinson's disease | journal = Journal of Molecular Medicine | volume = 82 | issue = 3 | pages = 163–74 | date = Mar 2004 | pmid = 14712351 | doi = 10.1007/s00109-003-0512-1 }}

{{cite journal | vauthors = Le W, Appel SH | title = Mutant genes responsible for Parkinson's disease | journal = Current Opinion in Pharmacology | volume = 4 | issue = 1 | pages = 79–84 | date = Feb 2004 | pmid = 15018843 | doi = 10.1016/j.coph.2003.09.005 }}

{{cite journal | vauthors = Abou-Sleiman PM, Healy DG, Wood NW | title = Causes of Parkinson's disease: genetics of DJ-1 | journal = Cell and Tissue Research | volume = 318 | issue = 1 | pages = 185–8 | date = Oct 2004 | pmid = 15503154 | doi = 10.1007/s00441-004-0922-6 }}

{{cite journal | vauthors = Pankratz N, Foroud T | title = Genetics of Parkinson disease | journal = NeuroRx | volume = 1 | issue = 2 | pages = 235–42 | date = Apr 2004 | pmid = 15717024 | pmc = 534935 | doi = 10.1602/neurorx.1.2.235 }}

{{cite journal | vauthors = Heutink P | title = PINK-1 and DJ-1--new genes for autosomal recessive Parkinson's disease | journal = Journal of Neural Transmission. Supplementum | volume = 70 | issue = 70 | pages = 215–9 | year = 2006 | pmid = 17017532 | doi = 10.1007/978-3-211-45295-0_33 | isbn = 978-3-211-28927-3 | series = Journal of Neural Transmission. Supplementa }}

{{cite journal | vauthors = Lev N, Roncevic D, Roncevich D, Ickowicz D, Melamed E, Offen D | title = Role of DJ-1 in Parkinson's disease | journal = Journal of Molecular Neuroscience | volume = 29 | issue = 3 | pages = 215–25 | year = 2007 | pmid = 17085780 | doi = 10.1385/JMN:29:3:215 }}

{{cite journal | vauthors = Nagakubo D, Taira T, Kitaura H, Ikeda M, Tamai K, Iguchi-Ariga SM, Ariga H | title = DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras | journal = Biochemical and Biophysical Research Communications | volume = 231 | issue = 2 | pages = 509–13 | date = Feb 1997 | pmid = 9070310 | doi = 10.1006/bbrc.1997.6132 }}

{{cite journal | vauthors = Taira T, Takahashi K, Kitagawa R, Iguchi-Ariga SM, Ariga H | title = Molecular cloning of human and mouse DJ-1 genes and identification of Sp1-dependent activation of the human DJ-1 promoter | journal = Gene | volume = 263 | issue = 1-2 | pages = 285–92 | date = Jan 2001 | pmid = 11223268 | doi = 10.1016/S0378-1119(00)00590-4 }}

{{cite journal | vauthors = 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 | title = Park7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36 | journal = American Journal of Human Genetics | volume = 69 | issue = 3 | pages = 629–34 | date = Sep 2001 | pmid = 11462174 | pmc = 1235491 | doi = 10.1086/322996 }}

{{cite journal | vauthors = Takahashi K, Taira T, Niki T, Seino C, Iguchi-Ariga SM, Ariga H | title = DJ-1 positively regulates the androgen receptor by impairing the binding of PIASx alpha to the receptor | journal = The Journal of Biological Chemistry | volume = 276 | issue = 40 | pages = 37556–63 | date = Oct 2001 | pmid = 11477070 | doi = 10.1074/jbc.M101730200 }}

{{cite journal | vauthors = 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 | title = Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism | journal = Science | volume = 299 | issue = 5604 | pages = 256–9 | date = Jan 2003 | pmid = 12446870 | doi = 10.1126/science.1077209 }}

{{cite journal | vauthors = 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 | title = Autosomal recessive early onset parkinsonism is linked to three loci: PARK2, PARK6, and PARK7 | journal = Neurological Sciences | volume = 23 Suppl 2 | issue = | pages = S59-60 | date = Sep 2002 | pmid = 12548343 | doi = 10.1007/s100720200069 }}

{{cite journal | vauthors = Niki T, Takahashi-Niki K, Taira T, Iguchi-Ariga SM, Ariga H | title = 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 | journal = Molecular Cancer Research | volume = 1 | issue = 4 | pages = 247–61 | date = Feb 2003 | pmid = 12612053 | doi = }}

{{cite journal | vauthors = Tao X, Tong L | title = Crystal structure of human DJ-1, a protein associated with early onset Parkinson's disease | journal = The Journal of Biological Chemistry | volume = 278 | issue = 33 | pages = 31372–9 | date = Aug 2003 | pmid = 12761214 | doi = 10.1074/jbc.M304221200 }}

{{cite journal | vauthors = Honbou K, Suzuki NN, Horiuchi M, Niki T, Taira T, Ariga H, Inagaki F | title = The crystal structure of DJ-1, a protein related to male fertility and Parkinson's disease | journal = The Journal of Biological Chemistry | volume = 278 | issue = 33 | pages = 31380–4 | date = Aug 2003 | pmid = 12796482 | doi = 10.1074/jbc.M305878200 }}

{{cite journal | vauthors = Dekker M, Bonifati V, van Swieten J, Leenders N, Galjaard RJ, Snijders P, Horstink M, Heutink P, Oostra B, van Duijn C | title = Clinical features and neuroimaging of PARK7-linked parkinsonism | journal = Movement Disorders | volume = 18 | issue = 7 | pages = 751–7 | date = Jul 2003 | pmid = 12815653 | doi = 10.1002/mds.10422 }}

{{cite journal | vauthors = 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 | title = L166P mutant DJ-1, causative for recessive Parkinson's disease, is degraded through the ubiquitin-proteasome system | journal = The Journal of Biological Chemistry | volume = 278 | issue = 38 | pages = 36588–95 | date = Sep 2003 | pmid = 12851414 | doi = 10.1074/jbc.M304272200 }}