Protein deglycase DJ-1, also known as Parkinson disease protein 7, is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

which in humans is encoded by the ''PARK7''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

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 deglycase DJ-1 is 20 kDa in size and composed of 189 amino acids with seven

β-strand The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a g ...

s and nine

α-helices The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues ear ...

in total and is present as a

dimer Dimer may refer to: * Dimer (chemistry), a chemical structure formed from two similar sub-units ** Protein dimer, a protein quaternary structure ** d-dimer * Dimer model, an item in statistical mechanics, based on ''domino tiling'' * Julius Dimer ...

. It belongs to the

peptidase A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the fo ...

C56 family of proteins. The protein structures of human protein DJ-1, ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...

'' chaperone Hsp31, YhbO and YajL and an Archaea protease are evolutionarily conserved.

Function

Under an oxidative condition, protein deglycase 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 Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily Detoxification, detoxify the reactive intermediates or to repair the resulting damage. Disturbances ...

. 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 The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in th ...

-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 Pyrroloquinoline quinone (PQQ), also called methoxatin'','' is a redox cofactor and antioxidant. Produced by bacteria, it is found in soil and foods such as kiwifruit, as well as human breast milk. Enzymes using PQQ as a redox cofactor are called ...

(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 Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

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

copper Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkis ...

and

mercury Mercury commonly refers to: * Mercury (planet), the nearest planet to the Sun * Mercury (element), a metallic chemical element with the symbol Hg * Mercury (mythology), a Roman god Mercury or The Mercury may also refer to: Companies * Merc ...

Clinical significance

Defects in this gene are the cause of autosomal recessive early-onset

Interactions

PARK7 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with: *

CASK A barrel or cask is a hollow cylindrical container with a bulging center, longer than it is wide. They are traditionally made of wooden staves and bound by wooden or metal hoops. The word vat is often used for large containers for liquids, u ...

, *

EFCAB6 EF-hand calcium-binding domain-containing protein 6 is a protein that in humans is encoded by the ''EFCAB6'' gene. Interactions EFCAB6 has been shown to interact with PARK7 and Androgen receptor The androgen receptor (AR), also known as NR ...

, and *

PIAS2 E3 SUMO-protein ligase PIAS2 is an enzyme that in humans is encoded by the ''PIAS2'' gene. Interactions Protein inhibitor of activated STAT2 has been shown to interact with: * Androgen receptor, * DNMT3A, * PARK7, and * UBE2I SUMO-conjugat ...

References

External links

* {{NLM content