Human Gene PARK7 (uc001aov.4)
  Description: Homo sapiens parkinson protein 7 (PARK7), transcript variant 2, mRNA.
RefSeq Summary (NM_001123377): 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. [provided by RefSeq, Jul 2008].
Transcript (Including UTRs)
   Position: hg19 chr1:8,021,714-8,045,342 Size: 23,629 Total Exon Count: 6 Strand: +
Coding Region
   Position: hg19 chr1:8,022,846-8,045,114 Size: 22,269 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviews
Model InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:8,021,714-8,045,342)mRNA (may differ from genome)Protein (169 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblExonPrimerGeneCardsGeneNetwork
H-INVHGNCHPRDLynxMalacardsMGI
neXtProtPubMedTreefamUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: PARK7_HUMAN
DESCRIPTION: RecName: Full=Protein DJ-1; EC=3.4.-.-; AltName: Full=Oncogene DJ1; AltName: Full=Parkinson disease protein 7; Flags: Precursor;
FUNCTION: 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.
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=173.4 uM for casein;
SUBUNIT: 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.
INTERACTION: P10275:AR; NbExp=6; IntAct=EBI-1164361, EBI-608057; Q9UER7:DAXX; NbExp=3; IntAct=EBI-1164361, EBI-77321; Q13158:FADD; NbExp=9; IntAct=EBI-1164361, EBI-494804; O94776:MTA2; NbExp=3; IntAct=EBI-1164361, EBI-1783035; Q6GQQ9:OTUD7B; NbExp=3; IntAct=EBI-1164361, EBI-527784;
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.
INDUCTION: By hydrogen peroxide and UV irradiation.
PTM: Sumoylated on Lys-130 by PIAS2 or PIAS4; which is enhanced after ultraviolet irradiation and essential for cell-growth promoting activity and transforming activity.
PTM: Cys-106 is easily oxidized to sulfinic acid.
PTM: Undergoes cleavage of a C-terminal peptide and subsequent activation of protease activity in response to oxidative stress.
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).
SIMILARITY: Belongs to the peptidase C56 family.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PARK7";
WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=P&genename=PARK7+%40+DJ-1";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): PARK7
CDC HuGE Published Literature: PARK7
Positive Disease Associations: Celiac disease , Colitis, Ulcerative
Related Studies:
  1. Celiac disease
    Dubois ,et al. Nat Genet 2010, Multiple common variants for celiac disease influencing immune gene expression , Nature genetics 2010 42- 4 : 295-302. [PubMed 20190752]
  2. Celiac Disease
    Patrick C A Dubois et al. Nature genetics 2010, Multiple common variants for celiac disease influencing immune gene expression., Nature genetics. [PubMed 20190752]
  3. Colitis, Ulcerative
    Carl A Anderson et al. Nature genetics 2011, Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47., Nature genetics. [PubMed 21297633]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: PARK7
Diseases sorted by gene-association score: parkinson disease 7, autosomal recessive early-onset* (1200), parkinson disease 6, early onset* (283), parkinson disease, juvenile, type 2* (157), park7-related parkinson disease* (100), amyotrophic lateral sclerosis-parkinsonism/dementia complex* (39), early-onset parkinson disease (26), snca-related parkinson disease (9), parkinson disease, late-onset (8), movement disease (7), parkinson disease 10 (7), supranuclear palsy, progressive (7), parkinson disease susceptibility (6), dementia, lewy body (5), parkinson disease 15, autosomal recessive (5), dementia (4), synucleinopathy (2), nervous system disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 137.56 RPKM in Adrenal Gland
Total median expression: 4494.51 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -40.60105-0.387 Picture PostScript Text
3' UTR -59.20228-0.260 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR006287 - DJ1
IPR002818 - ThiJ/PfpI

Pfam Domains:
PF01965 - DJ-1/PfpI family

SCOP Domains:
52317 - Class I glutamine amidotransferase-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1J42 - X-ray MuPIT 1P5F - X-ray MuPIT 1PDV - X-ray MuPIT 1PDW - X-ray MuPIT 1PE0 - X-ray MuPIT 1Q2U - X-ray MuPIT 1SOA - X-ray MuPIT 1UCF - X-ray MuPIT 2OR3 - X-ray MuPIT 2R1T - X-ray MuPIT 2R1U - X-ray MuPIT 2R1V - X-ray MuPIT 2RK3 - X-ray MuPIT 2RK4 - X-ray MuPIT 2RK6 - X-ray MuPIT 3B36 - X-ray MuPIT 3B38 - X-ray MuPIT 3B3A - X-ray MuPIT 3BWE - X-ray MuPIT 3CY6 - X-ray MuPIT 3CYF - X-ray MuPIT 3CZ9 - X-ray MuPIT 3CZA - X-ray MuPIT 3EZG - X-ray MuPIT 3F71 - X-ray MuPIT 3SF8 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q99497
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003713 transcription coactivator activity
GO:0003723 RNA binding
GO:0003729 mRNA binding
GO:0005102 receptor binding
GO:0005507 copper ion binding
GO:0005515 protein binding
GO:0008134 transcription factor binding
GO:0008233 peptidase activity
GO:0016532 superoxide dismutase copper chaperone activity
GO:0016684 oxidoreductase activity, acting on peroxide as acceptor
GO:0016787 hydrolase activity
GO:0019899 enzyme binding
GO:0019900 kinase binding
GO:0019955 cytokine binding
GO:0036470 tyrosine 3-monooxygenase activator activity
GO:0036478 L-dopa decarboxylase activator activity
GO:0036524 protein deglycase activity
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0044388 small protein activating enzyme binding
GO:0044390 ubiquitin-like protein conjugating enzyme binding
GO:0045296 cadherin binding
GO:0045340 mercury ion binding
GO:0050681 androgen receptor binding
GO:0051920 peroxiredoxin activity
GO:0070491 repressing transcription factor binding
GO:0097110 scaffold protein binding
GO:1903135 cupric ion binding
GO:1903136 cuprous ion binding
GO:1990381 ubiquitin-specific protease binding
GO:0001047 core promoter binding
GO:0003690 double-stranded DNA binding
GO:0003697 single-stranded DNA binding

Biological Process:
GO:0001933 negative regulation of protein phosphorylation
GO:0001963 synaptic transmission, dopaminergic
GO:0002866 positive regulation of acute inflammatory response to antigenic stimulus
GO:0006281 DNA repair
GO:0006469 negative regulation of protein kinase activity
GO:0006508 proteolysis
GO:0006517 protein deglycosylation
GO:0006914 autophagy
GO:0006954 inflammatory response
GO:0006974 cellular response to DNA damage stimulus
GO:0007005 mitochondrion organization
GO:0007265 Ras protein signal transduction
GO:0007338 single fertilization
GO:0008344 adult locomotory behavior
GO:0009438 methylglyoxal metabolic process
GO:0010273 detoxification of copper ion
GO:0010628 positive regulation of gene expression
GO:0010629 negative regulation of gene expression
GO:0018323 enzyme active site formation via L-cysteine sulfinic acid
GO:0019249 lactate biosynthetic process
GO:0030073 insulin secretion
GO:0031397 negative regulation of protein ubiquitination
GO:0032091 negative regulation of protein binding
GO:0032148 activation of protein kinase B activity
GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032757 positive regulation of interleukin-8 production
GO:0033138 positive regulation of peptidyl-serine phosphorylation
GO:0033234 negative regulation of protein sumoylation
GO:0033864 positive regulation of NAD(P)H oxidase activity
GO:0034599 cellular response to oxidative stress
GO:0034614 cellular response to reactive oxygen species
GO:0036471 cellular response to glyoxal
GO:0036526 peptidyl-cysteine deglycation
GO:0036527 peptidyl-arginine deglycation
GO:0036528 peptidyl-lysine deglycation
GO:0036529 protein deglycation, glyoxal removal
GO:0036530 protein deglycation, methylglyoxal removal
GO:0036531 glutathione deglycation
GO:0042177 negative regulation of protein catabolic process
GO:0042542 response to hydrogen peroxide
GO:0042593 glucose homeostasis
GO:0042743 hydrogen peroxide metabolic process
GO:0043066 negative regulation of apoptotic process
GO:0043523 regulation of neuron apoptotic process
GO:0043524 negative regulation of neuron apoptotic process
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0046295 glycolate biosynthetic process
GO:0046826 negative regulation of protein export from nucleus
GO:0050727 regulation of inflammatory response
GO:0050787 detoxification of mercury ion
GO:0050821 protein stabilization
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051444 negative regulation of ubiquitin-protein transferase activity
GO:0051583 dopamine uptake involved in synaptic transmission
GO:0051881 regulation of mitochondrial membrane potential
GO:0051897 positive regulation of protein kinase B signaling
GO:0051899 membrane depolarization
GO:0060081 membrane hyperpolarization
GO:0060548 negative regulation of cell death
GO:0060765 regulation of androgen receptor signaling pathway
GO:0070301 cellular response to hydrogen peroxide
GO:0090073 positive regulation of protein homodimerization activity
GO:0098869 cellular oxidant detoxification
GO:1900182 positive regulation of protein localization to nucleus
GO:1901215 negative regulation of neuron death
GO:1901671 positive regulation of superoxide dismutase activity
GO:1901984 negative regulation of protein acetylation
GO:1902177 positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
GO:1902903 regulation of supramolecular fiber organization
GO:1902958 positive regulation of mitochondrial electron transport, NADH to ubiquinone
GO:1903073 negative regulation of death-inducing signaling complex assembly
GO:1903094 negative regulation of protein K48-linked deubiquitination
GO:1903122 negative regulation of TRAIL-activated apoptotic signaling pathway
GO:1903168 positive regulation of pyrroline-5-carboxylate reductase activity
GO:1903178 positive regulation of tyrosine 3-monooxygenase activity
GO:1903181 positive regulation of dopamine biosynthetic process
GO:1903189 glyoxal metabolic process
GO:1903197 positive regulation of L-dopa biosynthetic process
GO:1903200 positive regulation of L-dopa decarboxylase activity
GO:1903202 negative regulation of oxidative stress-induced cell death
GO:1903204 negative regulation of oxidative stress-induced neuron death
GO:1903206 negative regulation of hydrogen peroxide-induced cell death
GO:1903208 negative regulation of hydrogen peroxide-induced neuron death
GO:1903377 negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
GO:1903384 negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway
GO:1903427 negative regulation of reactive oxygen species biosynthetic process
GO:1903428 positive regulation of reactive oxygen species biosynthetic process
GO:1903599 positive regulation of mitophagy
GO:1905259 negative regulation of nitrosative stress-induced intrinsic apoptotic signaling pathway
GO:2000157 negative regulation of ubiquitin-specific protease activity
GO:2000277 positive regulation of oxidative phosphorylation uncoupler activity
GO:2000679 positive regulation of transcription regulatory region DNA binding
GO:2000825 positive regulation of androgen receptor activity
GO:2001237 negative regulation of extrinsic apoptotic signaling pathway
GO:2001268 negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
GO:0045560 regulation of TRAIL receptor biosynthetic process

Cellular Component:
GO:0000785 chromatin
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005758 mitochondrial intermembrane space
GO:0005759 mitochondrial matrix
GO:0005783 endoplasmic reticulum
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005913 cell-cell adherens junction
GO:0016020 membrane
GO:0016605 PML body
GO:0030424 axon
GO:0043005 neuron projection
GO:0044297 cell body
GO:0045121 membrane raft
GO:0048471 perinuclear region of cytoplasm
GO:0070062 extracellular exosome
GO:0098793 presynapse
GO:0005747 mitochondrial respiratory chain complex I


-  Descriptions from all associated GenBank mRNAs
  AF021819 - Homo sapiens RNA-binding protein regulatory subunit mRNA, complete cds.
AK312000 - Homo sapiens cDNA, FLJ92274, highly similar to Homo sapiens Parkinson disease (autosomal recessive, early onset) 7 (PARK7), mRNA.
AK130886 - Homo sapiens cDNA FLJ27376 fis, clone UBA06221, highly similar to Homo sapiens RNA-binding protein regulatory subunit.
BC008188 - Homo sapiens Parkinson disease (autosomal recessive, early onset) 7, mRNA (cDNA clone MGC:5243 IMAGE:2901102), complete cds.
D61380 - Homo sapiens mRNA for DJ-1 protein, complete cds.
EU794641 - Homo sapiens epididymis secretory sperm binding protein Li 67p (HEL-S-67p) mRNA, complete cds.
AB464000 - Synthetic construct DNA, clone: pF1KB6832, Homo sapiens PARK7 gene for Parkinson disease 7, without stop codon, in Flexi system.
HQ447919 - Synthetic construct Homo sapiens clone IMAGE:100071277; CCSB002686_04 Parkinson disease (autosomal recessive, early onset) 7 (PARK7) gene, encodes complete protein.
AB073864 - Homo sapiens mRNA for DJ-1, complete cds.
DQ588074 - Homo sapiens piRNA piR-55186, complete sequence.
DQ588075 - Homo sapiens piRNA piR-55187, complete sequence.
DQ585430 - Homo sapiens piRNA piR-52542, complete sequence.
AK091679 - Homo sapiens cDNA FLJ34360 fis, clone FEBRA2014198.
AX747125 - Sequence 650 from Patent EP1308459.
JD248035 - Sequence 229059 from Patent EP1572962.
JD411135 - Sequence 392159 from Patent EP1572962.
JD195608 - Sequence 176632 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa05012 - Parkinson's disease

-  Other Names for This Gene
  Alternate Gene Symbols: AK130886, B2R4Z1, O14805, PARK7_HUMAN, Q6DR95, Q7LFU2, Q99497
UCSC ID: uc001aov.4
RefSeq Accession: NM_001123377
Protein: Q99497 (aka PARK7_HUMAN)

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene PARK7:
parkinson-overview (Parkinson Disease Overview)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: AK130886.1
exon count: 6CDS single in 3' UTR: no RNA size: 795
ORF size: 510CDS single in intron: no Alignment % ID: 99.87
txCdsPredict score: 1150.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.