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
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";
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]
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]
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.
ModBase Predicted Comparative 3D Structure on Q99497
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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.
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