DJ-1

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Protein-coding gene found in humans

title: "DJ-1" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public description: "Protein-coding gene found in humans" topic_path: "uncategorized" source: "https://en.wikipedia.org/wiki/DJ-1" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene found in humans ::

DJ1, also known as Parkinson disease protein 7, is a protein which in humans is encoded by the PARK7 gene. Its weak glyoxalase activity has been verified by many labs, however the reported protein deglycase activity is likely to be an artifact stemming from DJ-1's ability to destroy free methylglyoxal.

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.

Protein

The human protein 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. 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.

Function

DJ-1 was shown to prevent metabolite and protein damage caused by a glycolytic metabolite. This metabolite has been suggested and confirmed to be cyclic 3-phosphoglycerate (or cyclic 3-phosphoglyceric anhydride). Catalytic efficiency of DJ-1 as a hydrolase of cyclic 3-phosphoglyceric anhydride is 10,000 times higher than other reported enzymatic activities of DJ-1.

Under an oxidative condition, DJ-1 inhibits the aggregation of α-synuclein via its chaperone activity, 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. 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.

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.

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

DJ-1/PARK7 and its bacterial homologs: Hsp31, YhbO, and YajL can repair methylglyoxal and glyoxal glycated nucleotides. 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.

DNA repair

DJ-1 is a DNA damage response protein that is recruited to sites of DNA damage where it participates in the repair of DNA double-strand breaks through the processes of non-homologous end joining and homologous recombination. Evidence for a linkage between DNA damage and Parkinson's disease has been reported for decades. Recently evidence has been presented that defective DNA repair is linked specifically to DJ-1 mutation, and thus DJ-1 mutation likely contributes to Parkinson's disease pathogenesis.

Clinical significance

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

Interactions

PARK7 has been shown to interact with:

References

References

  1. "Entrez Gene: PARK7".
  2. (2019-12-06). "The apparent deglycase activity of DJ-1 results from the conversion of free methylglyoxal present in fast equilibrium with hemithioacetals and hemiaminals". Journal of Biological Chemistry.
  3. (May 2023). "Kinetic evidence in favor of glyoxalase III and against deglycase activity of DJ -1". Protein Science.
  4. "Uniprot: Q99497 - PARK7_HUMAN".
  5. (Aug 2003). "The crystal structure of DJ-1, a protein related to male fertility and Parkinson's disease". The Journal of Biological Chemistry.
  6. (Aug 2003). "Crystal structure of human DJ-1, a protein associated with early onset Parkinson's disease". The Journal of Biological Chemistry.
  7. (Nov 2003). "Crystal structures of human DJ-1 and Escherichia coli Hsp31, which share an evolutionarily conserved domain". The Journal of Biological Chemistry.
  8. (2022-01-25). "Parkinson's disease protein PARK7 prevents metabolite and protein damage caused by a glycolytic metabolite". Proceedings of the National Academy of Sciences.
  9. (2024-03-05). "DJ-1 protects proteins from acylation by catalyzing the hydrolysis of highly reactive cyclic 3-phosphoglyceric anhydride". Nature Communications.
  10. (Nov 2004). "DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation". PLOS Biology.
  11. (Mar 2006). "The oxidation state of DJ-1 regulates its chaperone activity toward alpha-synuclein". Journal of Molecular Biology.
  12. (August 2019). "A role for DJ-1 against oxidative stress in the mammalian retina". Neurosci Lett.
  13. (2013). "DJ-1-dependent regulation of oxidative stress in the retinal pigment epithelium (RPE)". PLOS ONE.
  14. (Jul 2008). "Pyrroloquinoline quinone prevents oxidative stress-induced neuronal death probably through changes in oxidative status of DJ-1". Biological & Pharmaceutical Bulletin.
  15. (2013). "Parkinson disease protein DJ-1 binds metals and protects against metal-induced cytotoxicity.". Journal of Biological Chemistry.
  16. (July 2017). "Guanine glycation repair by DJ-1/Park7 and its bacterial homologs". Science.
  17. (August 2022). "DJ -1 is not a deglycase and makes a modest contribution to cellular defense against methylglyoxal damage in neurons". Journal of Neurochemistry.
  18. (May 2023). "Nuclear DJ-1 Regulates DNA Damage Repair via the Regulation of PARP1 Activity". Int J Mol Sci.
  19. (Jan 2003). "Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism". Science.
  20. (2014). "Neuron-specific protein interactions of Drosophila CASK-β are revealed by mass spectrometry". Frontiers in Molecular Neuroscience.
  21. (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.
  22. (Oct 2001). "DJ-1 positively regulates the androgen receptor by impairing the binding of PIASx alpha to the receptor". The Journal of Biological Chemistry.

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