PARK7 (Parkinsonism associated deglycase)

2016-04-01 Valentina La Cognata , Sebastiano Cavallaro Affiliation

Identity

HGNC

LOCATION

Location Cytogenetic location: 1p36.23; Molecular location: Chromosome 1; Start 7961654; Stop 7985282based on Genome Browser Human Dec. 2013 (GRCh38/hg38) Assembly [Link to chromosome band 1p36]

IMAGE

LEGEND

Figure 1 displays the human chromosome 1 (NCBI Reference Sequence NC_000001.11) and relative localization and orientation of PARK7 and flanking genes. PARK7 is represented in red. Further genes (UTS2, TNFRSF9, ERRFI1) and a non-coding RNA (LOC105376694) map in this locus.

LOCUSID

11315

ALIAS

DJ-1,DJ1,GATD2,HEL-S-67p

Abstract

PARK7 (also called DJ-1 or Parkinsonism associated deglycase) is a pleiotropic protein belonging to the peptidase C56 family. It acts as positive regulator of androgen receptor-dependent transcription, redox-sensitive chaperone, sensor for oxidative stress, and apparently protects neurons against oxidative stress and cell death. Dysfunctions in PARK7 are related to autosomal recessive early-onset Parkinson disease 7 and cancer forms. Here, we review some major data on PARK7, concerning the genetic structure, the transcription regulation, the encoded protein and functions, and its implication in human diseases.

DNA/RNA

Figure 2 displays the two full-length Reference Sequences of PARK7 gene (NCBI - Nucleotide Database). Corresponding GenBank Accession Numbers are indicated on the left. Exons are represented as boxes (blue for coding regions and white for non-coding), whereas the dashed line indicates intronic regions. The green triangle specifies the start codon, while the red one designates the stop codon.

Figure 3 displays the structures of the currently known PARK7 mRNA splicing variants listed in Ensembl. Each mRNA variant is indicated with a number corresponding to that indicated in Table 1. Transcript variants are classified as coding mRNAs (black) and non-coding (gray).

Description

DJ-1 maps on the distal part of the short arm of chromosome 1, cytoband 1p36.23 (Figure 1). It spans about 24 kb and includes eight exons (Figure 2). The first two exons (1A and 1B) are noncoding and alternatively spliced in the DJ-1 mRNAs (Bonifati, Rizzu, Squitieri, et al., 2003).

Transcription

Currently, the NCBI RefSeq database annotates two representative transcripts as full-length PARK7 mRNAs (Figure 2). However, a total of 10 spliced variants is reported in the Ensembl database http://www.ensembl.org(Figure 3). The majority of mRNAs contain a 570 bp ORF, encoding a protein of 189 aa. Two shorter transcripts (PARK7-003 lacking exon 4, and PARK7-010 starting at an inner transcription point) produce smaller proteins (169 and 160 aa respectively) (Table 2 and Fig. 3). Other transcripts do not encode proteins and are processed via the NMD (non-sense mediated decay) mechanism.
Table 1.

#	Name	Ensembl Transcript ID	bp	Biotype	Protein
1	PARK7-004	ENST00000493373	624	Protein coding	189aa
2	PARK7-002	ENST00000338639	949	Protein coding	189aa
3	PARK7-007	ENST00000460192	567	Processed transcript	No protein
4	PARK7-001	ENST00000493678	1088	Protein coding	189aa
5	PARK7-003	ENST00000377493	795	Protein coding	169aa
6	PARK7-008	ENST00000465354	949	Processed transcript	No rotein
7	PARK7-005	ENST00000377491	977	Protein coding	189aa
8	PARK7-006	ENST00000377488	783	Protein coding	189aa
9	PARK7-009	ENST00000497113	670	Processed transcript	No protein
10	PARK7-010	ENST00000469225	711	Protein coding	160aa

Pseudogene

PGOHUM00000239770: Chr. 12, Start Coordinate 49988931, Stop Coordinate 49989471 according toGenome BrowserHuman Dec. 2013 (GRCh38/hg38) Assembly
PGOHUM00000236716: Chr. 9, Start Coordinate 98680419, Stop Coordinate 98680983according to Genome BrowserHuman Dec. 2013 (GRCh38/hg38) Assembly

Proteins

Figure 4 shows the crystallographic structure of DJ-1 protein. This protein is a dimer composed of two portions, monomer A represented in purple and monomer B represented in green. Adapted from (Wilson et al., 2003).

Description

X-ray crystallographic examination of DJ-1 protein structure indicates that it exists as a dimer (Figure 4)(Wilson et al., 2003). It contains domains found in heat shock chaperones and belongs to the ThiJ/PfpI family. This family (pfam01965) includes: ThiJ, a protein involved in thiamine biosynthesis in prokaryotes; PfpI (so-called from P. furious protease I) and other bacterial proteases; araC and other bacterial transcription factors; and the glutamine amidotransferases family (including bacteria catalases) (Bonifati, Rizzu, Squitieri, et al., 2003).

Expression

DJ-1 is a ubiquitous protein, highly expressed in almost all cells and tissue (Figure 5). Distribution studies indicate that DJ-1 is preferentially expressed in testis, brain and kidney. In the brain, DJ-1 is expressed in both neurons and glial cells. The expression level of DJ-1 is increased under oxidative stress conditions both in PD and other neurodegenerative diseases(Ariga et al., 2013). DJ-1 is also frequently overexpressed in the several tumor types (Cao et al., 2015).

Figure 5 (adapted from PROTEOMICS DB - www.proteomicsdb.org) shows the central and peripheral distribution of DJ-1 in human tissues. It is a ubiquitous protein, expressed in almost all human body systems.

Localisation

Subcellular localization: DJ-1 is mainly localized in the nucleus, cytoplasm, and mitochondria and is secreted into culture medium or serum, cerebrospinal fluid, saliva and nipple fluid(Ariga, 2015). DJ-1 is translocated from the cytoplasm to nucleus upon addition of a mitogen to the culture medium, while it translocates to mitochondria after oxidative stress (Junn et al., 2009).

Figure 6 (fromGeneCards database http://www.genecards.org/ and based on Compartments http://compartments.jensenlab.org/) shows the subcellular localizations of DJ-1 into cellular structures. Data are derived from database annotations, automatic text mining of the biomedical literature, and sequence-based predictions. The confidence of each association is indicated with numbers (the higher number corresponds to a greater confidence).

Function

The product of DJ-1 is an 189 amino acidic highly conserved multifunctional protein belonging to the peptidase C56 family (Lev et al., 2006). It mainly acts as regulator of transcription, redox-sensitive chaperone, sensor for oxidative stress, cysteine protease, and seems to protect neurons from ROS-induced apoptosis (Figure 7) (Xu et al., 2005; Ariga et al., 2013).
The oxidative stress sensor activity is carried out by three cysteine residues at C46, C53 and C106: under oxidative stress conditions, C106 is firstly oxidized from SH to SOH, SO2H and to SO3H form. The other cysteine residues then follow the same process of oxidation.
The regulation of transcription is mediated by DJ-1 binding with various transcription factors without directly tie up to DNA. Transcription factors or modified proteins identified so far include TP53, the androgen receptorAR and its regulatory proteins, the polypyrimidine tract-binding protein-associated splicing factor(SFPQ), KEAP1, an inhibitor for nuclear factor erythroid-2 related factor 2 (NFE2L2), the sterol regulatory element-binding protein (SREBP), Ras-responsive element-binding protein (RREB1), and signal transducer and activator of transcription1 (STAT1) (Ariga, 2015).
DJ-1 is also involved in the activation or repression of cell growth and cell death signaling pathways. Specifically, this polypeptide modulates p53 activity, the PI3K/Akt pathway by interacting with PTEN, and intervenes in the Raf/Erk pathway together with ras (Ariga, 2015). To this regard, it should be reminded that the first identified DJ-1 function was its oncogene activity transforming mouse NIH3T3 cells in cooperation with activated ras (Nagakubo et al., 1997).

Figure 7 summarizes the functions of DJ-1 and related diseases. It is though that excess of activation or loss of function of DJ-1 triggers the onset of various diseases, including cancer and oxidative stress-related diseases. Abbreviations: PD - Parkinsons Disease, FAP - familial amyloid polyneuropathy; COPD - chronic obstructive pulmonary disease. Adapted from (Ariga, 2015).

Homology

The PARK7 Gene Tree shows a great evolutionary conservation across species (Figure 8). The internal nodes of the phylogenetic tree are annotated for duplication (red boxes) and speciation (blue boxes) events, which correspond to paralogs and orthologs genes respectively.

Figure 8. The PARK7 Gene Tree shows the maximum likelihood phylogenetic tree representing the evolutionary history of this gene, constructed using the alignment of a representative protein for each species (green bars). This Gene tree has been generated by Ensembl (GeneTree ENSGT00390000001231).

Mutations

Somatic

PARK7 Mutations	Exon	References
Ex1-5del(g.07561_21658del14098)	EX1-5	(Bonifati, Rizzu, van Baren, et al., 2003)
Ex1-5dup (breakpoints not mapped)	EX1-5	(Macedo et al., 2009)
Ex2del (breakpoints not mapped)	EX2	(Guo et al., 2010)
Ex5del (breakpoints not mapped)	EX5	(Djarmati et al., 2004)
Ex5-7del (breakpoints not mapped)	EX5-7	(Hedrich et al., 2004)
c.-122_-107del (g.10539_10554del16)	5UTR	(Keyser et al., 2009)
Leu10Pro (g.11658T>C)	EX2	(Guo et al., 2008)
Met26Ile (g.11707G>A)	EX2	(Abou-Sleiman et al., 2003)
Ala39Ser (g.14192G>T)	EX3	(Tang et al., 2006)
Glu64Asp (g.14269G>C)	EX3	(Hering et al., 2004)
Gly78 (g.18230C>T)	EX2	(Abou-Sleiman et al., 2003)
IVS4+8_9insA (g.18256_18257insA)	IVS4	(Tarantino et al., 2009)
Arg98Gln (g.19778G>A)	EX5	(Abou-Sleiman et al., 2003) (Lockhart et al., 2004) (Healy et al., 2004) (Clark et al., 2004) (Pankratz et al., 2006)
Arg98(g.19779G>A)	EX5	(Abou-Sleiman et al., 2003)
Ala104Thr(g.19795G>A)	EX5	Clark et al., 2004)
IVS5+2_12del (g.19809_19819del11)	IVS5	(Hedrich et al., 2004)
Asp149Ala (g.33774A>C)	EX7	(Abou-Sleiman et al., 2003)
Pro158del (g.33799_33801delGCC)	EX7	Macedo et al., 2009)
Thr160 (g.33808C>A)	EX7	(Pankratz et al., 2006)
Glu163Lys (g.33815G>A)	EX7	(Annesi et al., 2005)
Leu166Pro (g.33825T>C)	EX7	(Bonifati, Rizzu, van Baren, et al., 2003)
Ala167 (g.33829A>G)	EX7	(Abou-Sleiman et al., 2003)
Ala171Ser (g.33839G>T)	EX7	(Clark et al., 2004)
Lys175Glu (g.33851A>G)	EX7	(Nuytemans et al., 2009)
Ala179Thr (g.33863G>A)	EX7	(Macedo et al., 2009) (Nuytemans et al., 2009)
Val186 (g.33886T>C)	EX7	(Hering et al., 2004)
c.*120insA (g.34018_34019insA)	EX7	(Abou-Sleiman et al., 2003)
c.*203G>A (g.34101G>A)	EX7	(Abou-Sleiman et al., 2003)

Table 2 displays the currently known PARK7 genetic mutations related to familial Parkinsons Disease. Details are available at the Parkinson Disease Mutation Database (http://www.molgen.vib-ua.be/PDMutDB/).

Figure 9 shows the overall distribution of PARK7 somatic mutations in cancer listed in COSMIC Database (http://cancer.sanger.ac.uk/cosmic) (March 2016). The exact number of collected somatic mutations in different cancer types is indicated in the data labels.

Germinal

A wide spectrum of mutations in PARK7 have been identified in familial Parkinsons Disease patients from different ethnicities. Mutations include missense mutations in coding and UTR regions, frame-shifts, copy number variations, and splice sites alterations (Table 2).

Somatic

Along with the germinal mutations occurring in Parkinsons Disease, genetic defects have also been observed in solid tumors. A list of the known cancer-derived mutations is available at the COSMIC Database and is summarized in Figure 9.

Epigenetics

No currently known epigenetic mechanismsregulating PARK7.

Implicated in

Entity name

Parkinsons Disease

Note

Mutations in PARK7 are the less common cause of autosomal recessive Parkinsonism (~ 1% of early-onset PD) (Lockhart et al., 2004; Moore et al., 2005). The first identified mutations were a large homozygous deletion and a missense mutation (L166P) identified in both Italian and Dutch consanguineous families (van Duijn et al., 2001; Bonifati, Rizzu, Squitieri, et al., 2003). The other observed familial mutations are summarized in Table 2.

Entity name

Familial amyloid polyneuropathy

Note

Transthyretin (TTR), a protein causing familial amyloidotic polyneuropathy (FAP), is a substrate of DJ-1 protease (Koide-Yoshida et al., 2007). In normal conditions, both TTR and DJ-1 are secreted into the culture medium. Under oxidative stress, TTR but not DJ-1 is secreted into the culture medium, resulting in the aggregation of TTR protein. Mirror images of both the expression patterns and solubility of DJ-1 and TTR have been observed in tissues of FAP patients, and the unoxidized form of DJ-1 is secreted into the serum of FAP patients. These results suggest that oxidative stress abrogates secretion of DJ-1 and that secreted DJ-1 degrades aggregated TTR to protect against the onset of FAP (Koide-Yoshida et al., 2007).

Entity name

Chronic obstructive pulmonary disease

Disease

Chronic obstructive pulmonary disease (COPD) is caused by cigarette smoking and oxidative stress. Malhotra et al. assessed the expression of NFE2L2 (NRF2) and DJ-1 in non-COPD and smoker COPD lungs and in cigarette smoke-exposed human lung epithelial cells (Beas2B) and mice (Malhotra et al., 2008). COPD patient lungs showed significantly decreased DJ-1 levels. Exposure of Bea2B cells to cigarette smoke caused oxidative modification and enhanced proteasomal degradation of DJ-1 protein. Disruption of DJ-1 in mouse lungs, mouse embryonic fibroblasts, and Beas2B cells lowered NRF2 protein stability and impaired antioxidant induction in response to cigarette smoke. Overall, DJ-1 expression was negatively associated with severity of COPD (Malhotra et al., 2008).

Entity name

Type II Diabetes

Note

The expression of DJ-1 is reduced in pancreatic islets of patients with type 2 diabetes mellitus (T2DM). Under non-diabetic conditions, DJ-1 expression increases in mouse and human islets during aging. Jain et al. demonstrated that, in mouse islets, DJ-1 prevents an increase in reactive oxygen species and preserves mitochondrial integrity and physiology, prerequisites for glucose-stimulated insulin secretion(Jain et al., 2012). Accordingly, DJ-1-deficient mice developed glucose intolerance and reduced βcell area as they age or gain weight. These data suggested that DJ-1 is more generally involved in age- and lifestyle-related human diseases and show that DJ-1 plays a key role in glucose homeostasis (Jain et al., 2012).

Entity name

Stroke

Note

Loss of DJ-1 increases the sensitivity to excitotoxicity and ischemia, whereas expression of DJ-1 can reverse this sensitivity and provide protection (Aleyasin et al., 2007). Importantly, DJ-1 expression decreases markers of oxidative stress after stroke insult in vivo, suggesting that DJ-1 protects through alleviation of oxidative stress (Aleyasin et al., 2007). Consistent with this finding, (Aleyasin et al., 2007) demonstrated the essential role of the oxidation-sensitive cysteine-106 residue in the neuroprotective activity of DJ-1 after stroke.

Entity name

Prostate cancer

Note

he intracellular level of the DJ-1 polypeptide in prostatic benign hyperplasia BPH-1 cells is inducible and results markedly increased after exposure to stress-inducing agents (H 2 O 2 and mitomycin C). The expression of DJ-1 is relatively high in PC-3 cells at the constitutive level, and incubation with the same cytotoxic drugs does not further modulate the polypeptide expression. Both cytotoxic agents activate the apoptotic pathway in the benign prostatic cells but not in PC-3 cells, which are resistant to their action (Hod, 2004).

Entity name

Renal carcinoma

Note

The expression level of DJ-1 mRNA in a series of 176 renal cell carcinomas (RCC) has been measured by (Sitaram et al., 2009). The level of DJ-1 has been demonstrated significantly elevated in clear cell RCC compared with papillary RCC and kidney cortex tissue.

Entity name

Hepatocellular carcinoma

Note

DJ-1 was found significantly up-regulated in 149 hepatocellular carcinomas (HCC). DJ-1 expression correlates with preoperative alpha-fetoprotein, liver cirrhosis, vein invasion, differentiation and overall survival, thus suggesting DJ-1 as a candidate prognostic biomarker of HCC (S. Liu et al., 2010).

Entity name

Ovarian carcinoma

Note

The expression and clinical role of DJ-1 and its putative association with transcriptional regulators specific proteins (SP1 and SP3) were investigated in ovarian carcinoma by (Davidson et al., 2008). RT-PCR reactions and immunohistochemistry were used to analyze the expression levels of DJ-1, Sp1 and Sp3 mRNAs and PTEN protein. DJ-1 expression resulted positively associated with Sp1 expression in effusions, and with Sp1 and Sp3 expression in solid tumors. Overall, results show DJ-1 is frequently expressed in advanced-stage ovarian carcinoma at all anatomical sites and is co-expressed with its transcriptional regulators Sp1 and Sp3. In contrast, PTEN expression is infrequent in this disease.

Entity name

Breast cancer

Note

Expression of DJ-1 was examined by immunohistochemistry and in-situ hybridization in 273 breast invasive ductal carcinomas (IDCs) and 41 breast ductal carcinomas in situ (DCISs) and in cancer cell lines (MDA-MB-231). DJ-1 protein expression resulted lower than adjacent non-cancerous epithelium in 6 of the 41 DCISs and in 146 of the 273 IDCs. Patients with IDC and low DJ-1 expression had significant shorter disease-free survival and overall survival. Low expression of DJ-1 protein seems to be predictive of poor outcome in patients with IDC (Tsuchiya et al., 2012). Furthermore, RS/DJ-1 was found to be secreted in the breast cell line SUM-44 and in sera of diagnosed patients with breast cancer (Le Naour et al., 2001).

Entity name

Acute leukemia

Note

DJ-1 was found overexpressed in acute leukemia (AL) patient samples and leukemia cell lines, giving the first clue that DJ-1 overexpression might be involved in leukemogenesis and/or disease progression of AL (H. Liu et al., 2008). Inactivation of DJ-1 by RNA-mediated interference (RNAi) in leukemia cell lines K562 and HL60 resulted in inhibition of the proliferation potential and enhancement of the sensitivity of leukemia cells to chemotherapeutic drug etoposide(H. Liu et al., 2008).

Entity name

Cervical cancer

Note

Normal cervical epithelium and patient-matched high-grade squamous intraepithelial lesions (HSIL) with cervical carcinoma tissue were compared by using laser capture microdissection and 2-D DIGE (Arnouk et al., 2009). Significant expression changes were observed with 53 spots corresponding to 23 unique proteins, including DJ-1. Results were confirmed by immunohistochemistry using either frozen sections from the same cohort or formalin fixed paraffin embedded samples from a tissue microarray. These markers can have potential applications for increasing the predictive value of current screening methods (Arnouk et al., 2009).

Entity name

Non-small cell lung carcinoma

Note

A proteomic approach using two-dimensional gels coupled with mass spectrometry was used in non-small cell lung carcinoma samples to identify proteins altered when treated with paclitaxel, a chemotherapic that activates mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase and a MEK inhibitor (MacKeigan et al., 2003). This combined treatment uniquely altered the proteins RS/DJ-1 (RNA-binding regulatory subunit/DJ-1 PARK7) and RhoGDIalpha (MacKeigan et al., 2003).

Entity name

Endometrial cancer

Note

RT-PCR and Western blotting were performed to determine the DJ-1 expression in 100 surgical specimens of endometrial cancer tissues, paired tumor-adjacent tissues, and 30 surgical specimens of normal endometrium tissues (Morelli et al., 2014).DJ-1 expression in endometrial cancer tissues was higher than in tumor-adjacent tissues and normal endometrial tissues. At the same time, it was associated with signs of cancer progression, including differentiation, myometrial invasion depth, and presence of lymph node metastasis. Overall, high DJ-1 expression seems to be negatively correlated with apoptosis, and it may be part of the mechanisms for the development, invasion, and metastasis in endometrial cancer (Morelli et al., 2014).

Entity name

Thyroid cancer

Note

A comparative proteome analysis was performed by (Giusti et al., 2008) in order to examine the global changes of fine needle aspiration fluid protein patterns of two variants of malignant papillary thyroid cancer PTC (classical variant and tall cell variant) respect to the controls. Changes in protein expression were identified using two-dimensional electrophoresis (2DE) and peptide mass finger printing via MALDI-TOF mass spectrometry (MS), as well as Western blot analysis. A significant statistical up-regulation of 17 protein spots including DJ-1 was observed in classical PTC and/or tall cell variant PTC with respect to controls(Giusti et al., 2008).

Entity name

Pancreas adenocarcinoma

Note

To identify potential novel biomarkers for pancreatic ductal adenocarcinoma (PDAC) from pancreatic juice, (Tian et al., 2008) carried out gel electrophoresis (DIGE) and tandem mass spectrometry (MS/MS) to compare the pancreatic juice profiling from 9 PDAC patients and 9 cancer-free controls. Of the differently expressed proteins, three up-regulated proteins in pancreatic cancer juice were selected for validation by Western blot and immunohistochemistry, including DJ-1. Up-regulation of DJ-1 was associated with better differentiation (Tian et al., 2008). In another study, the DJ-1 protein expression in tissue specimens from 41 patients was evaluated by immunohistochemistry and associated with a negative impact of chemotherapy with gemcitabine on patients survival. Therefore, DJ-1 has been suggested as prognostic markers that express resistance of pancreatic cancer patients to chemotherapy with gemcitabine (Tsiaousidou et al., 2013).

Entity name

Laryngeal squamous cell carcinoma

Note

A study conducted by (Shen et al., 2011)aimed to explore the correlation between DJ-1 gene and survivin gene BIRC5 in laryngeal squamous cell carcinoma. The expression levels of DJ-1 gene and survivin gene in 82 laryngeal carcinoma tissues from patients and 82 negative surgical margin tissue samples were measured by immunohistochemistry and the relationship with clinicopathologic parameters was assessed. Positive correlations were found between expression levels and patients clinical parameters in laryngeal carcinoma tissues and tumor stages, but not with lymph node metastasis. The DJ-1 gene expression level was also related to cell differentiation. DJ-1 and survivin play a vital role in the occurrence and development of laryngeal carcinoma. DJ-1 may promote the carcinogenesis of laryngeal cells by up-regulating the survivin gene expression (Shen et al., 2011).

Entity name

Esophageal squamous cell carcinoma

Note

The expression of DJ-1 in 81 esophageal squamous cell carcinoma (ESCC) tumors, 31 paired non neoplastic esophageal epithelia, and 19 paired ESCC lymph node metastases was analyzed by (Yuen et al., 2008). They found that cytoplasmic DJ-1 expression was significantly higher in ESCC and ESCC lymph node metastases than in non neoplastic esophageal epithelium. ESCC specimens with high distant metastatic potential also had a significantly higher level of nuclear DJ-1 expression. A high level of nuclear DJ-1 was significantly associated with poorer patient survival in the cohort (P = 0.028). DJ-1 expression was significantly associated with pAkt, whereas nuclear DJ-1 expression was significantly correlated with nuclear expression of DAXX. These results suggest that phosphatidylinositol 3-kinase pathway and Daxx-regulated apoptosis might be important in DJ-1-mediated ESCC progression. In conclusion, results suggest that DJ-1 plays a very important role in transformation and progression of ESCC and may be used as a prognostic marker in ESCC.

Entity name

Other malignancies

Note

Increased levels of DJ-1 expression have been observed in other kinds of cancer cells and tissues, including gastric cancer (Shimwell et al., 2012; Li et al., 2013), supraglottic cancer (Zhu et al., 2012), cholangiocarcinoma (Kawase et al., 2009), glioma/glioblastomas(Hinkle et al., 2011; Wang et al., 2013), bladder carcinoma (Lee et al., 2012) and melanoma (Pardo et al., 2006). Increased levels of DJ-1 expression in cancer cells are parallel to severity of cancer with poor prognosis, including metastasis and invasion (Ariga, 2015).

Article Bibliography

Pubmed ID	Last Year	Title	Authors
12953260	2003	The role of pathogenic DJ-1 mutations in Parkinson's disease.	Abou-Sleiman PM et al
18003894	2007	The Parkinson's disease gene DJ-1 is also a key regulator of stroke-induced damage.	Aleyasin H et al
16240358	2005	DJ-1 mutations and parkinsonism-dementia-amyotrophic lateral sclerosis complex.	Annesi G et al
26027820	2015	Common mechanisms of onset of cancer and neurodegenerative diseases.	Ariga H et al
23766857	2013	Neuroprotective function of DJ-1 in Parkinson's disease.	Ariga H et al
19834583	2009	Characterization of Molecular Markers Indicative of Cervical Cancer Progression.	Arnouk H et al
12446870	2003	Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism.	Bonifati V et al
25498803	2015	DJ-1 as a human oncogene and potential therapeutic target.	Cao J et al
15254937	2004	Analysis of an early-onset Parkinson's disease cohort for DJ-1 mutations.	Clark LN et al
17949781	2008	Expression and clinical role of DJ-1, a negative regulator of PTEN, in ovarian carcinoma.	Davidson B et al
15108293	2004	Detection of Parkin (PARK2) and DJ1 (PARK7) mutations in early-onset Parkinson disease: Parkin mutation frequency depends on ethnic origin of patients.	Djarmati A et al
18665625	2008	Fine-needle aspiration of thyroid nodules: proteomic analysis to identify cancer biomarkers.	Giusti L et al
18785233	2008	Mutation analysis of Parkin, PINK1, DJ-1 and ATP13A2 genes in Chinese patients with autosomal recessive early-onset Parkinsonism.	Guo JF et al
20146068	2010	Mutation analysis of Parkin, PINK1 and DJ-1 genes in Chinese patients with sporadic early onset parkinsonism.	Guo JF et al
15210917	2004	Assessment of a DJ-1 (PARK7) polymorphism in Finnish PD.	Healy DG et al
14872018	2004	DJ-1 (PARK7) mutations are less frequent than Parkin (PARK2) mutations in early-onset Parkinson disease.	Hedrich K et al
15365989	2004	Novel homozygous p.E64D mutation in DJ1 in early onset Parkinson disease (PARK7).	Hering R et al
20497343	2011	DJ-1 expression in glioblastomas shows positive correlation with p53 expression and negative correlation with epidermal growth factor receptor amplification.	Hinkle DA et al
15258905	2004	Differential control of apoptosis by DJ-1 in prostate benign and cancer cells.	Hod Y et al
22611253	2012	Age- and diet-dependent requirement of DJ-1 for glucose homeostasis in mice with implications for human type 2 diabetes.	Jain D et al
18711745	2009	Mitochondrial localization of DJ-1 leads to enhanced neuroprotection.	Junn E et al
19569727	2009	Differential LC-MS-based proteomics of surgical human cholangiocarcinoma tissues.	Kawase H et al
19825160	2009	Identification of a novel functional deletion variant in the 5'-UTR of the DJ-1 gene.	Keyser RJ et al
17487420	2007	DJ-1 degrades transthyretin and an inactive form of DJ-1 is secreted in familial amyloidotic polyneuropathy.	Koide-Yoshida S et al
11705844	2001	Proteomics-based identification of RS/DJ-1 as a novel circulating tumor antigen in breast cancer.	Le Naour F et al
22740940	2012	Overexpression of DJ-1 and HSP90α, and loss of PTEN associated with invasive urothelial carcinoma of urinary bladder: Possible prognostic markers.	Lee H et al
17085780	2006	Role of DJ-1 in Parkinson's disease.	Lev N et al
24155657	2013	High-expression of DJ-1 and loss of PTEN associated with tumor metastasis and correlated with poor prognosis of gastric carcinoma.	Li Y et al
18722352	2008	Expression and role of DJ-1 in leukemia.	Liu H et al
21410067	2010	Increased DJ-1 and its prognostic significance in hepatocellular carcinoma.	Liu S et al
14985393	2004	DJ-1 mutations are a rare cause of recessively inherited early onset parkinsonism mediated by loss of protein function.	Lockhart PJ et al
18973254	2009	Genotypic and phenotypic characteristics of Dutch patients with early onset Parkinson's disease.	Macedo MG et al
18556627	2008	Decline in NRF2-regulated antioxidants in chronic obstructive pulmonary disease lungs due to loss of its positive regulator, DJ-1.	Malhotra D et al
16022590	2005	Molecular pathophysiology of Parkinson's disease.	Moore DJ et al
24614826	2014	DJ-1 in endometrial cancer: a possible biomarker to improve differential diagnosis between subtypes.	Morelli M et al
9070310	1997	DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras.	Nagakubo D et al
19405094	2009	Relative contribution of simple mutations vs. copy number variations in five Parkinson disease genes in the Belgian population.	Nuytemans K et al
16997464	2006	Mutations in DJ-1 are rare in familial Parkinson disease.	Pankratz N et al
16570276	2006	The characterization of the invasion phenotype of uveal melanoma tumour cells shows the presence of MUC18 and HMG-1 metastasis markers and leads to the identification of DJ-1 as a potential serum biomarker.	Pardo M et al
21556124	2011	Significance and relationship between DJ-1 gene and surviving gene expression in laryngeal carcinoma.	Shen Z et al
22968650	2012	Macrophage migration inhibitory factor and DJ-1 in gastric cancer: differences between high-incidence and low-incidence areas.	Shimwell NJ et al
19384955	2009	The PTEN regulator DJ-1 is associated with hTERT expression in clear cell renal cell carcinoma.	Sitaram RT et al
16632486	2006	Association of PINK1 and DJ-1 confers digenic inheritance of early-onset Parkinson's disease.	Tang B et al
18722801	2009	Compound heterozygosity in DJ-1 gene non-coding portion related to parkinsonism.	Tarantino P et al
18706098	2008	Proteomic analysis identifies MMP-9, DJ-1 and A1BG as overexpressed proteins in pancreatic juice from pancreatic ductal adenocarcinoma patients.	Tian M et al
24280570	2013	B7H4, HSP27 and DJ-1 molecular markers as prognostic factors in pancreatic cancer.	Tsiaousidou A et al
22385318	2012	Clinical significance of DJ-1 as a secretory molecule: retrospective study of DJ-1 expression at mRNA and protein levels in ductal carcinoma of the breast.	Tsuchiya B et al
23714193	2013	The positive correlation between DJ-1 and β-catenin expression shows prognostic value for patients with glioma.	Wang C et al
12855764	2003	The 1.1-A resolution crystal structure of DJ-1, the protein mutated in autosomal recessive early onset Parkinson's disease.	Wilson MA et al
15790595	2005	The Parkinson's disease-associated DJ-1 protein is a transcriptional co-activator that protects against neuronal apoptosis.	Xu J et al
19064576	2008	DJ-1 could predict worse prognosis in esophageal squamous cell carcinoma.	Yuen HF et al
23151319	2012	Tumorigenesis role and clinical significance of DJ-1, a negative regulator of PTEN, in supraglottic squamous cell carcinoma.	Zhu XL et al
11462174	2001	Park7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36.	van Duijn CM et al

Other Information

Locus ID:

NCBI: 11315
MIM: 602533
HGNC: 16369
Ensembl: ENSG00000116288

Variants:

dbSNP: 11315
ClinVar: 11315
TCGA: ENSG00000116288
COSMIC: PARK7

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000116288	ENST00000338639	Q99497
ENSG00000116288	ENST00000338639	V9HWC2
ENSG00000116288	ENST00000377488	Q99497
ENSG00000116288	ENST00000377488	V9HWC2
ENSG00000116288	ENST00000377491	Q99497
ENSG00000116288	ENST00000377491	V9HWC2
ENSG00000116288	ENST00000377493	K7ELW0
ENSG00000116288	ENST00000469225	K7EN27
ENSG00000116288	ENST00000493373	Q99497
ENSG00000116288	ENST00000493373	V9HWC2
ENSG00000116288	ENST00000493678	Q99497
ENSG00000116288	ENST00000493678	V9HWC2

Expression (GTEx)

100

150

200

250

300

350

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Parkinson's disease	KEGG	hsa05012

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
37674036	2024	A Complex Interplay of DJ-1, LRRK2, and Nrf2 in the Regulation of Mitochondrial Function in Cypermethrin-Induced Parkinsonism.	0
38460098	2024	DJ-1 protects cell death from a mitochondrial oxidative stress due to GBA1 deficiency.	2
37674036	2024	A Complex Interplay of DJ-1, LRRK2, and Nrf2 in the Regulation of Mitochondrial Function in Cypermethrin-Induced Parkinsonism.	0
38460098	2024	DJ-1 protects cell death from a mitochondrial oxidative stress due to GBA1 deficiency.	2
34918581	2023	PARK7/DJ-1 inhibition decreases invasion and proliferation of uveal melanoma cells.	1
36586770	2023	WTAP-mediated m6A modification on circCMTM3 inhibits hepatocellular carcinoma ferroptosis by recruiting IGF2BP1 to increase PARK7 stability.	9
36603736	2023	Parkinson's disease-associated 18 bp promoter variant of DJ-1 alters REST binding and regulates its expression.	1
36768161	2023	Searching for Biomarkers in the Blood of Patients at Risk of Developing Parkinson's Disease at the Prodromal Stage.	3
36820886	2023	Parkinsonism-Associated Protein DJ-1 Is an Antagonist, Not an Eraser, for Protein Glycation.	6
37060572	2023	Kinetic evidence in favor of glyoxalase III and against deglycase activity of DJ-1.	5
37072827	2023	PARK7/DJ-1 in microglia: implications in Parkinson's disease and relevance as a therapeutic target.	6
37289979	2023	Disease-Modifying Effects of Vincamine Supplementation in Drosophila and Human Cell Models of Parkinson's Disease Based on DJ-1 Deficiency.	0
37749450	2023	TrkB inhibition of DJ-1 degradation promotes the growth and maintenance of cancer stem cell characteristics in hepatocellular carcinoma.	0
38125697	2023	DJ-1: A Potential Biomarker Related to Prognosis, Chemoresistance, and Expression of Microenvironmental Chemokine in HR-Positive Breast Cancer.	0
34918581	2023	PARK7/DJ-1 inhibition decreases invasion and proliferation of uveal melanoma cells.	1

Citation

Valentina La Cognata ; Sebastiano Cavallaro

PARK7 (Parkinsonism associated deglycase)

Atlas Genet Cytogenet Oncol Haematol. 2016-04-01

Online version: http://atlasgeneticsoncology.org/gene/41639/favicon/teaching-explorer/humanGenome