PARK7 (parkinson protein 7)

Parkinson's disease locus DJ-1 (PARK7) is a differentially expressed transcript. DJ-1 plays a physiologic role in protection of erythroid cells from oxidant damage, a function unmasked in the context of oxidative stress. PARK7 belongs to the peptidase C56 family of proteins. It acts as a positive regulator of androgen receptor-dependent transcription. It may also function as a redox-sensitive chaperone, as a sensor for oxidative stress, and it apparently protects neurons against oxidative stress and cell death. Mutations in the DJ-1 gene are associated with rare forms of autosomal recessive early-onset Parkinson's disease (PD). DJ-1/p53 interactions contribute to apoptosis resistance in clonal myeloid cells and may serve as a prognostic marker in patients with myelodysplastic syndromes (MDS). DJ-1 regulates redox signaling kinase pathways and acts as a transcriptional regulator of antioxidative gene batteries. Therefore, DJ-1 is an important redox-reactive signaling intermediate controlling oxidative stress after ischemia, upon neuroinflammation, and during age-related neurodegenerative processes. Augmenting DJ-1 activity might provide novel approaches to treating chronic neurodegenerative illnesses such as Parkinson's disease and acute damage such as stroke.

PARK7 (parkinson protein 7) Related Areas

Cancer>>Apoptosis>>Oxidative Stress>>PARK7/DJ-1

Neuroscience>>Neurodegeneration>>Parkinson's Disease>>PARK7/DJ-1

PARK7 (parkinson protein 7) Alternative Names

PARK7, DJ-1, CTA-215D11.1, DJ1, FLJ27376, FLJ34360, FLJ92274 [Homo sapiens]

Park7, DJ-1, RP23-272N19.5, Dj1 [Mus musculus]

Summaries for PARK7 (parkinson protein 7)

Entrez Gene summary for PARK7 (parkinson protein 7):

The product of this gene belongs to the peptidase C56 family of proteins. It acts as a positive regulator of androgen receptor-dependent transcription. It may also function as a redox-sensitive chaperone, as a sensor for oxidative stress, and it apparently protects neurons against oxidative stress and cell death. Defects in this gene are the cause of autosomal recessive early-onset Parkinson disease 7. Two transcript variants encoding the same protein have been identified for this gene

OMIM - description for PARK7 (parkinson protein 7):

Nagakubo et al. (1997) used yeast 2-hybrid screening of a HeLa cell library to clone a cDNA that encodes a novel 189-amino acid protein, termed DJ1. Northern blot analysis revealed that DJ1 is ubiquitously expressed as a 1.0-kb transcript. Western blot analysis and immunofluorescence showed that the DJ1 protein is present in both nuclei and cytoplasm of HeLa cells. After addition of serum to cells, DJ1 expression increased and the protein translocated from the cytoplasm to nuclei. A search of the GenBank protein database revealed that DJ1 has approximately 40% identity to the 198-amino acid protein product of the E. coli thiazole monophosphate biosynthesis (ThiJ) gene. A homolog also exists in the nematode C. elegans. Northern blot analysis by Bonifati et al. (2003) showed ubiquitous expression of the DJ1 transcript, particularly in liver, skeletal muscle, and kidney. In the brain, expression was also ubiquitous, with higher levels of the transcript in subcortical regions, such as the caudate nucleus, the thalamus, the substantia nigra, and the hippocampus, that are more affected in parkinson disease (see MOLECULAR GENETICS).

Wikipedia summary for PARK7 (parkinson protein 7):

Parkinson disease (autosomal recessive, early onset) 7, also known as PARK7, is a protein which in humans is encoded by the PARK7 gene.It is also known as DJ-1.

Human PARK7 (parkinson protein 7) Protein General Information

 

• Protein names: Recommended name: Protein DJ-1
• Sequence length: 189 AA.
• Sequence similarities: Belongs to the peptidase C56 family.
• Post-translational modification: Sumoylated on Lys-130 by PIAS2 or PIAS4; which is enhanced after ultraviolet irradiation and essential for cell-growth promoting activity and transforming activity. Ref.21 Cys-106 is easily oxidized to sulfinic acid. Undergoes cleavage of a C-terminal peptide and subsequent activation of protease activity in response to oxidative stress.
• Subunit structure: Homodimer. Binds EFCAB6/DJBP and PIAS2. Part of a ternary complex containing PARK7, EFCAB6/DJBP and AR. Interacts (via N-terminus) with OTUD7B. Interacts with BBS1, HIPK1, CLCF1 and MTERF
• Subcellular location: Cytoplasm. Nucleus. Mitochondrion. Note: Under normal conditions, located predominantly in the cytoplasm and, to a lesser extent, in the nucleus and mitochondrion. Translocates to the mitochondrion and subsequently to the nucleus in response to oxidative stress and exerts an increased cytoprotective effect against oxidative damage. Detected in tau inclusions in brains from neurodegenerative disease patients
• Tissue specificity: Highly expressed in pancreas, kidney, skeletal muscle, liver, testis and heart. Detected at slightly lower levels in placenta and brain. Detected in astrocytes, Sertoli cells, spermatogonia, spermatids and spermatozoa.
• Involvement in disease: Defects in PARK7 are the cause of Parkinson disease type 7 (PARK7) [MIM:606324]. A neurodegenerative disorder characterized by resting tremor, postural tremor, bradykinesia, muscular rigidity, anxiety and psychotic episodes. PARK7 has onset before 40 years, slow progression and initial good response to levodopa. Some patients may show traits reminiscent of amyotrophic lateral sclerosis-parkinsonism/dementia complex (Guam disease).

General information above from UniProt

Function for PARK7 (parkinson protein 7) Protein

UniProtKB:

Protects cells against oxidative stress and cell death. Plays a role in regulating expression or stability of the mitochondrial uncoupling proteins SLC25A14 and SLC25A27 in dopaminergic neurons of the substantia nigra pars compacta and attenuates the oxidative stress induced by calcium entry into the neurons via L-type channels during pacemaking. Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death. May act as an atypical peroxiredoxin-like peroxidase that scavenges hydrogen peroxide. Following removal of a C-terminal peptide, displays protease activity and enhanced cytoprotective action against oxidative stress-induced apoptosis. Stabilizes NFE2L2 by preventing its association with KEAP1 and its subsequent ubiquitination. Binds to OTUD7B and inhibits its deubiquitinating activity. Enhances RELA nuclear translocation. Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress. Required for correct mitochondrial morphology and function and for autophagy of dysfunctional mitochondria. Regulates astrocyte inflammatory responses. Acts as a positive regulator of androgen receptor-dependent transcription. Prevents aggregation of SNCA. Plays a role in fertilization. Has no proteolytic activity. Has cell-growth promoting activity and transforming activity. May function as a redox-sensitive chaperone.

Genatlas:

• PARK7 (parkinson protein 7) function as a positive regulator of androgen receptor
• PARK7 (parkinson protein 7) is involved in the oxidative stress response
• PARK7 (parkinson protein 7) protecte against mitochondrial damage and may be protecting neurons from various stressful stimuli
• neuroprotective transcriptional co-activator that may act in concert with NONO and SFPQ to regulate the expression of a neuroprotective genetic program
• PARK7 (parkinson protein 7) has a functional role in scavenging mitochondrial H2O2 because of its physiological action as an atypical peroxiredoxin-like peroxidase
• multi-functional protein that plays roles in transcriptional regulation and anti-oxidative stress function
• PARK7 (parkinson protein 7) is involved in cancer by promoting Ras signaling and suppressing PTEN-induced apoptosis
• PARK7 (parkinson protein 7) may play roles in coordinating responses to oxidative damage and suppression of cell death
• PARK7 (parkinson protein 7) protect cells against hypoxia-induced cell death and is required for their adaptation to severe hypoxic stress
• degrades aggregated TTR to protect against the onset of FAP (familial amyloidotic polyneuropathy)
• upstream activator of HIF1 function in cancer cells and its oncogenic activity stems from its ability to increase a cell resistance to hypoxic stress
• PARK7 (parkinson protein 7) plays roles in transcriptional regulation and anti-oxidative stress
• crucial for full activation of AKT1 upon oxidative injury, which serves as one explanation for the protective effects of PARK7
• exerts an important role in the regulation of the AKT1 pathway in response to oxidative stress and neuronal protection
• important for proper mitochondrial function and acts downstream of, or in parallel to, PINK1
• PARK7 (parkinson protein 7) is in a pathway parallel to that of PINK1/parkin and both of these pathways, and their carefully balanced activity, are critical for mitochondrial function
• PARK7 (parkinson protein 7) works in parallel to the PINK1/parkin pathway to maintain mitochondrial function in the presence of an oxidative environment

Homology for human PARK7 (parkinson protein 7)

• homolog to rattus Cap1
• homolog to E.coli Thij

Phenotype Information for PARK7 (parkinson protein 7)

• Gene/Locus: DJ1, PARK7
• Phenotype: Amyotrophic lateral sclerosis-Parkinsonism/dementia complex 2 Parkinson disease 7, autosomal recessive early-onset

Phenotype Information for PARK7 (parkinson protein 7) from OMIM (Online Mendelian Inheritance in Man)