PARK7/DJ-1 is a multifunctional protein linked to autosomal recessive early-onset Parkinson disease (PARK7). It functions as a GSH-independent glyoxalase converting methylglyoxal/glyoxal to lactate/glycolate, an oxidative stress sensor via Cys-106 oxidation, a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregation, a copper chaperone for SOD1, and a transcriptional coactivator. DJ-1 stabilizes NFE2L2/Nrf2 by preventing Keap1-mediated degradation, modulates NF-kappaB signaling via OTUD7B/Cezanne binding, and participates in mitochondrial quality control as part of the PINK1-PRKN-DJ-1 complex. The protein deglycase activity initially attributed to DJ-1 is controversial, with evidence suggesting apparent deglycase activity results from glyoxalase-mediated equilibrium shifts rather than direct deglycation. DJ-1 forms a homodimer with Cys-106 as the critical active-site residue for most activities.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006979 response to oxidative stress | IBA GO_REF:0000033 | ACCEPT | Summary: DJ-1 is a well-established oxidative stress response protein. Cys-106 oxidation serves as a redox sensor, and DJ-1 protects cells from oxidative damage through multiple mechanisms including Nrf2 stabilization, chaperone activity, and mitochondrial protection (PMID:17015834, PMID:15502874, PMID:18711745). See also PARK7-deep-research-falcon.md for comprehensive literature review. Reason: Core function of DJ-1 supported by extensive experimental evidence across multiple studies. IBA annotation is appropriate at this level. Supporting Evidence: PMID:17015834 DJ-1 stabilizes Nrf2 by preventing association with its inhibitor protein, Keap1, and Nrf2's subsequent ubiquitination PMID:15502874 DJ-1 functions as a redox-sensitive molecular chaperone that is activated in an oxidative cytoplasmic environment file:human/PARK7/PARK7-deep-research-falcon.md DJ-1 is best characterized as an oxidative stress sensor and multifunctional cytoprotective protein |
| GO:0046295 glycolate biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: DJ-1 glyoxalase activity converts glyoxal to glycolate, confirmed by Lee et al. 2012 (PMID:22523093). This is a direct product of the glyoxalase reaction. Reason: Glycolate is the confirmed product of DJ-1's glyoxalase activity on glyoxal. Well-supported by enzymology. Supporting Evidence: PMID:22523093 human DJ-1 and its homologs of the mouse and Caenorhabditis elegans are novel types of glyoxalase, converting glyoxal or methylglyoxal to glycolic or lactic acid, respectively |
| GO:1903189 glyoxal metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: DJ-1 metabolizes glyoxal via its GSH-independent glyoxalase activity, converting it to glycolate (PMID:22523093). This is a core enzymatic function. Reason: Glyoxal metabolism is a well-established enzymatic activity of DJ-1, consistently demonstrated across studies. Supporting Evidence: PMID:22523093 converting glyoxal or methylglyoxal to glycolic or lactic acid, respectively, in the absence of glutathione |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: DJ-1 is predominantly cytoplasmic, consistently shown across many studies (PMID:18711745, PMID:15983381, PMID:19822128). Reason: Cytoplasmic localization is the primary location for DJ-1 and is well-established. Supporting Evidence: PMID:18711745 under basal conditions DJ-1 is present mostly in the cytoplasm and to a lesser extent in mitochondria and nucleus |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: DJ-1 localizes to the nucleus, with enhanced nuclear translocation under oxidative stress (PMID:22683601, PMID:18711745, PMID:15790595). Nuclear function includes transcriptional coactivation. Reason: Nuclear localization is well-established by IDA evidence from multiple labs and is functionally relevant for transcriptional coactivation. Supporting Evidence: PMID:22683601 Nuclear translocation of DJ-1 during oxidative stress-induced neuronal cell death |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: DJ-1 localizes to mitochondria, particularly under oxidative stress conditions. It binds mitochondrial complex I and maintains its activity (PMID:19822128, PMID:18711745, PMID:15944198). Reason: Mitochondrial localization is well-established and functionally significant for DJ-1's role in mitochondrial quality control and complex I maintenance. Supporting Evidence: PMID:19822128 DJ-1 binds to mitochondrial complex I and maintains its activity PMID:18711745 Mitochondrial localization of DJ-1 leads to enhanced neuroprotection |
| GO:0016684 oxidoreductase activity, acting on peroxide as acceptor | IBA GO_REF:0000033 | ACCEPT | Summary: DJ-1 has been reported to eliminate hydrogen peroxide and protect cells from H2O2-induced death (PMID:14749723, PMID:24567322). The peroxidase-like activity is Cys-106 dependent. However, this is a weak activity and may not represent a major catalytic function. Reason: IBA annotation reflects the conserved redox chemistry of the DJ-1 superfamily. H2O2 detoxification activity has been experimentally demonstrated, even if it may not be the primary enzymatic function. Supporting Evidence: PMID:24567322 DJ-1 is a copper chaperone acting on SOD1 activation |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation consistent with IBA and multiple IDA evidence for nuclear localization of DJ-1 (PMID:18711745, PMID:15790595, PMID:22683601). Reason: Redundant with IBA but correct. Nuclear localization is well-established. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation consistent with IBA and multiple IDA evidence for cytoplasmic localization of DJ-1 (PMID:18711745, PMID:15983381). Reason: Redundant with IBA but correct. Cytoplasm is the primary localization. |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation consistent with IBA and IDA evidence for mitochondrial localization of DJ-1 (PMID:18711745, PMID:19822128, PMID:15944198). Reason: Redundant with IBA but correct. Mitochondrial localization is well-established. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000120 | ACCEPT | Summary: DJ-1 has been reported in the ER, supported by IDA evidence from PMID:31536960 (mitochondrial interactome study). UniProt also notes ER localization. Reason: ER localization supported by experimental data and consistent with DJ-1's role in ER stress-induced apoptosis protection (PMID:14652021). |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: DJ-1 associates with the plasma membrane via palmitoylation at Cys-46, Cys-53, and Cys-106, and regulates lipid raft-dependent endocytosis in astrocytes. UniProt notes cell membrane localization via lipid anchor. Reason: Plasma membrane association supported by palmitoylation data from UniProt (PMID:23847046). |
| GO:0045121 membrane raft | IEA GO_REF:0000044 | ACCEPT | Summary: DJ-1 associates with lipid rafts via palmitoylation and regulates lipid raft-dependent endocytosis in astrocytes. UniProt notes this localization. Reason: Lipid raft localization supported by palmitoylation studies. This may be more relevant to astrocyte biology than neuronal core function. |
| GO:1903190 glyoxal catabolic process | IEA GO_REF:0000108 | ACCEPT | Summary: Logically inferred from glyoxal metabolic process annotation. DJ-1 catabolizes glyoxal to glycolate via its glyoxalase activity (PMID:22523093). Reason: Consistent with core glyoxalase function. Logical inference from well-supported parent term. |
| GO:0005515 protein binding | IPI PMID:15983381 Interaction of DJ-1 with Daxx inhibits apoptosis signal-regu... | MARK AS OVER ANNOTATED | Summary: DJ-1 interacts with Daxx to inhibit apoptosis signal-regulating kinase 1 (ASK1) activity (PMID:15983381). Protein binding is uninformative; more specific terms like scaffold protein binding or kinase binding would be preferable. Reason: Generic protein binding does not capture the functional significance of DJ-1-Daxx interaction in ASK1 regulation. |
| GO:0005515 protein binding | IPI PMID:17510388 DJ-1 binds androgen receptor directly and mediates its activ... | MARK AS OVER ANNOTATED | Summary: DJ-1 binds androgen receptor directly (PMID:17510388). More specific nuclear androgen receptor binding (GO:0050681) is annotated separately. Reason: Redundant with more specific GO:0050681 nuclear androgen receptor binding annotation from the same reference. |
| GO:0005515 protein binding | IPI PMID:18000879 Novel interaction partners of Bardet-Biedl syndrome proteins... | MARK AS OVER ANNOTATED | Summary: DJ-1 identified as novel interaction partner of Bardet-Biedl syndrome proteins in a proteomics study (PMID:18000879). The functional relevance is unclear. Reason: Generic protein binding from high-throughput interactome study. Functional significance of BBS protein interaction not established. |
| GO:0005515 protein binding | IPI PMID:20127688 Increased interaction between DJ-1 and the Mi-2/ nucleosome ... | MARK AS OVER ANNOTATED | Summary: DJ-1 interacts with the Mi-2/NuRD nucleosome remodelling and deacetylase complex, with increased interaction during cellular stress (PMID:20127688). Reason: Generic protein binding is uninformative. The specific interaction with chromatin remodelling complex is more meaningfully captured by other annotations. |
| GO:0005515 protein binding | IPI PMID:21097510 DJ-1 enhances cell survival through the binding of Cezanne, ... | MARK AS OVER ANNOTATED | Summary: DJ-1 binds OTUD7B/Cezanne, a negative regulator of NF-kappaB (PMID:21097510). More specific ubiquitin-specific protease binding (GO:1990381) is annotated separately. Reason: Redundant with more specific GO:1990381 ubiquitin-specific protease binding from the same reference. |
| GO:0005515 protein binding | IPI PMID:21785459 DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspas... | MARK AS OVER ANNOTATED | Summary: DJ-1 interacts with FADD to inhibit TRAIL-induced apoptosis by blocking pro-caspase-8 recruitment (PMID:21785459). More specific scaffold protein binding (GO:0097110) is annotated separately. Reason: Redundant with more specific GO:0097110 scaffold protein binding annotation from the same reference. |
| GO:0005515 protein binding | IPI PMID:23743200 DJ-1 cooperates with PYCR1 in cell protection against oxidat... | MARK AS OVER ANNOTATED | Summary: DJ-1 cooperates with PYCR1 in cell protection against oxidative stress (PMID:23743200). More specific enzyme binding is annotated from the same reference. Reason: Generic protein binding is uninformative. The DJ-1-PYCR1 interaction is more specifically captured by enzyme binding annotation. |
| GO:0005515 protein binding | IPI PMID:24947010 DJ-1 interacts with RACK1 and protects neurons from oxidativ... | MARK AS OVER ANNOTATED | Summary: DJ-1 interacts with RACK1 to protect neurons from oxidative stress-induced apoptosis (PMID:24947010). Reason: Generic protein binding is uninformative. The DJ-1-RACK1 interaction should be captured by more specific terms. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: High-throughput proteome-scale interactome mapping study (PMID:25416956). Generic protein binding from large-scale screen. Reason: Generic protein binding from high-throughput study adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:26752685 FIH Regulates Cellular Metabolism through Hydroxylation of t... | MARK AS OVER ANNOTATED | Summary: DJ-1 identified as interactor in study of FIH regulation of OTUB1 (PMID:26752685). Peripheral finding. Reason: Generic protein binding from interactome study. Not informative for DJ-1 function. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: DJ-1 identified in interactome mapping of neurodegenerative disease proteins (PMID:32814053). High-throughput study. Reason: Generic protein binding from large-scale neurodegenerative disease interactome mapping. |
| GO:0042802 identical protein binding | IPI PMID:15502874 DJ-1 is a redox-dependent molecular chaperone that inhibits ... | MODIFY | Summary: DJ-1 forms homodimers that are essential for function. Shendelman et al. showed DJ-1 chaperone activity requires dimerization (PMID:15502874). However, homodimerization activity (GO:0042803) is a more specific term. Reason: Identical protein binding is less specific than protein homodimerization activity (GO:0042803), which better describes DJ-1's obligate homodimer. Proposed replacements: protein homodimerization activity |
| GO:0042802 identical protein binding | IPI PMID:15983381 Interaction of DJ-1 with Daxx inhibits apoptosis signal-regu... | MODIFY | Summary: DJ-1 homodimerization demonstrated in study of DJ-1-Daxx interaction (PMID:15983381). More specific GO:0042803 protein homodimerization activity is the better term. Reason: Should use more specific term GO:0042803 protein homodimerization activity. Proposed replacements: protein homodimerization activity |
| GO:0042802 identical protein binding | IPI PMID:24947010 DJ-1 interacts with RACK1 and protects neurons from oxidativ... | MODIFY | Summary: DJ-1 homodimerization confirmed in context of RACK1 interaction study (PMID:24947010). More specific GO:0042803 protein homodimerization activity is the better term. Reason: Should use more specific term GO:0042803 protein homodimerization activity. Proposed replacements: protein homodimerization activity |
| GO:0002866 positive regulation of acute inflammatory response to antigenic stimulus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: DJ-1 modulates inflammatory responses, including in microglia where DJ-1 loss leads to pro-inflammatory states. However, positive regulation of acute inflammatory response to antigenic stimulus is overly specific and not well-supported for DJ-1's actual role. DJ-1 generally dampens inflammation rather than promoting it. Reason: This term suggests DJ-1 positively regulates acute inflammatory responses, but DJ-1 loss is associated with increased inflammation. The term likely derives from mouse data but is overly specific and potentially misleading. |
| GO:0005758 mitochondrial intermembrane space | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DJ-1 localizes to mitochondria, but specific localization to the intermembrane space is not well-characterized for human DJ-1. Most studies describe general mitochondrial localization. Reason: Mitochondrial localization is established, but intermembrane space specificity is from ortholog transfer and may not be well-validated in human. |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DJ-1 localizes to mitochondria, but specific localization to the mitochondrial matrix is primarily based on ortholog data. Some studies suggest association with inner membrane/matrix fractions. Reason: Mitochondrial matrix localization is plausible but not specifically validated for human DJ-1 with strong evidence. |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation consistent with multiple IDA evidence for cytosolic localization (PMID:19229105, PMID:14662519, PMID:15944198). DJ-1 is primarily cytosolic. Reason: Cytosol is the primary localization of DJ-1, supported by extensive experimental evidence. |
| GO:0006979 response to oxidative stress | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation redundant with IBA annotation for the same term. Core function of DJ-1. Reason: Redundant with IBA but correct. Response to oxidative stress is the central function of DJ-1. |
| GO:0007005 mitochondrion organization | IEA GO_REF:0000107 | ACCEPT | Summary: DJ-1 is required for correct mitochondrial morphology and function, and for autophagy of dysfunctional mitochondria (UniProt, PMID:16632486, PMID:19229105). Part of PINK1-PRKN-DJ-1 complex. Reason: Mitochondrion organization is supported by DJ-1's role in the PINK1-Parkin-DJ-1 mitochondrial quality control axis. |
| GO:0008021 synaptic vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Synaptic vesicle localization for DJ-1 is based on ortholog transfer. While DJ-1 functions in neurons, specific synaptic vesicle localization is not well-established for human DJ-1. Reason: Plausible given neuronal expression, but not strongly validated for human DJ-1 directly. May reflect mouse data. |
| GO:0010273 detoxification of copper ion | IEA GO_REF:0000107 | ACCEPT | Summary: DJ-1 binds copper and protects against metal-induced cytotoxicity (PMID:23792957). Also acts as copper chaperone for SOD1 (PMID:24567322). IEA consistent with experimental evidence. Reason: Copper detoxification supported by direct experimental evidence including IMP from PMID:23792957. |
| GO:0010628 positive regulation of gene expression | IEA GO_REF:0000107 | ACCEPT | Summary: DJ-1 positively regulates gene expression through transcriptional coactivation and Nrf2 stabilization (PMID:17015834, PMID:15790595, PMID:16731528). This is a broad but accurate annotation. Reason: Consistent with DJ-1's role as transcriptional coactivator and Nrf2 stabilizer. |
| GO:0019826 oxygen sensor activity | IEA GO_REF:0000107 | MODIFY | Summary: DJ-1 senses oxidative stress via Cys-106 oxidation, but this is more accurately described as a redox sensor than an oxygen sensor per se. The term oxygen sensor activity implies direct oxygen sensing, which is not DJ-1's primary mechanism. Reason: DJ-1 is a redox sensor (via Cys-106 oxidation to sulfinic acid) rather than a direct oxygen sensor. Detection of oxidative stress (GO:0070994) is more accurate. Proposed replacements: detection of oxidative stress |
| GO:0030073 insulin secretion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DJ-1 is involved in maintenance of glucose homeostasis in pancreatic islets in an age- and diet-dependent manner (UniProt, PMID:22611253). The insulin secretion role is primarily established in mouse. Reason: Insulin secretion role is from mouse studies transferred by orthology. This is a secondary phenotypic role, not a core molecular function of DJ-1. |
| GO:0031397 negative regulation of protein ubiquitination | IEA GO_REF:0000107 | ACCEPT | Summary: DJ-1 negatively regulates protein ubiquitination, specifically preventing Nrf2 ubiquitination by Keap1 (PMID:17015834) and regulating VHL-mediated ubiquitination (PMID:24899725). Supported by experimental evidence. Reason: Consistent with IDA evidence from PMID:17015834 and PMID:24899725 showing DJ-1 prevents ubiquitination of specific targets. |
| GO:0034599 cellular response to oxidative stress | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation consistent with extensive experimental evidence for DJ-1's role in cellular response to oxidative stress (PMID:15983381, PMID:19703902, PMID:22683601). Reason: Core function. Cellular response to oxidative stress is well-established for DJ-1. |
| GO:0036471 cellular response to glyoxal | IEA GO_REF:0000107 | ACCEPT | Summary: DJ-1 responds to glyoxal by metabolizing it via glyoxalase activity (PMID:22523093). Consistent with core enzymatic function. Reason: Supported by IDA evidence from PMID:22523093. Core glyoxalase function. |
| GO:0042177 negative regulation of protein catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: DJ-1 negatively regulates protein degradation by stabilizing Nrf2 (preventing Keap1-mediated proteasomal degradation, PMID:17015834) and through PINK1 stabilization. Consistent with experimental evidence. Reason: Supported by DJ-1's role in preventing ubiquitin-dependent protein degradation of targets like Nrf2 and PINK1. |
| GO:0042593 glucose homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DJ-1 involvement in glucose homeostasis is primarily from mouse pancreatic islet studies (PMID:22611253). This is a secondary, tissue-specific phenotype. Reason: Glucose homeostasis role is from mouse studies. Not a core molecular function of DJ-1. |
| GO:0043005 neuron projection | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DJ-1 is expressed in neurons and localized to neuron projections based on ortholog data. Consistent with its role in Parkinson disease and neuronal protection. Reason: Neuron projection localization is plausible given DJ-1's neuronal functions but is based on ortholog transfer. |
| GO:0044297 cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DJ-1 localization to cell body is from ortholog transfer. Consistent with ubiquitous cytoplasmic expression. Reason: Cell body localization is a general localization annotation that adds little beyond cytoplasm/cytosol annotations. |
| GO:0046295 glycolate biosynthetic process | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation redundant with IBA for glycolate biosynthetic process. Consistent with glyoxalase activity converting glyoxal to glycolate (PMID:22523093). Reason: Redundant with IBA but correct. Glycolate production is a direct consequence of glyoxalase activity on glyoxal. |
| GO:0050727 regulation of inflammatory response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DJ-1 regulates inflammatory responses, particularly in microglia where DJ-1 loss leads to dysregulated innate immune pathways including NLRP3 and cGAS/STING (PARK7-deep-research-falcon.md). Also modulates NF-kappaB via OTUD7B binding (PMID:21097510). Reason: Inflammatory response regulation is a secondary downstream effect of DJ-1's oxidative stress function, not a core molecular function. |
| GO:0050787 detoxification of mercury ion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DJ-1 binds mercury ions and enhances protection against metal-induced cytotoxicity (PMID:23792957). Mercury binding is experimentally demonstrated. Reason: Mercury ion detoxification is supported by experimental evidence but is likely a secondary consequence of DJ-1's metal-binding capacity rather than a core function. |
| GO:0050821 protein stabilization | IEA GO_REF:0000107 | ACCEPT | Summary: DJ-1 stabilizes multiple proteins including Nrf2 (PMID:17015834) and PINK1 (PMID:19229105). Protein stabilization is a core protective mechanism. Reason: Protein stabilization is a key mechanism by which DJ-1 exerts its protective functions, particularly Nrf2 stabilization. |
| GO:0051920 peroxiredoxin activity | IEA GO_REF:0000107 | MODIFY | Summary: DJ-1 has been reported to eliminate hydrogen peroxide via Cys-106 (PMID:14749723), and the IBA annotation for oxidoreductase activity acting on peroxide as acceptor is related. However, calling DJ-1 a peroxiredoxin is misleading as DJ-1 does not belong to the peroxiredoxin family and its peroxidase activity is weak. Reason: DJ-1 is not a peroxiredoxin. It has weak peroxidase-like activity but the peroxiredoxin term implies membership in that enzyme family. Oxidoreductase activity acting on peroxide as acceptor (GO:0016684) is more appropriate. Proposed replacements: oxidoreductase activity, acting on peroxide as acceptor |
| GO:0070994 detection of oxidative stress | IEA GO_REF:0000107 | ACCEPT | Summary: DJ-1 detects oxidative stress through Cys-106 oxidation, which serves as a molecular switch controlling its protective activities. This is a core function. Reason: Detection of oxidative stress via Cys-106 oxidation is one of the best-characterized functions of DJ-1. |
| GO:1900242 regulation of synaptic vesicle endocytosis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Regulation of synaptic vesicle endocytosis by DJ-1 is based on ortholog transfer. This is an overly specific neuronal phenotype not well-established for human DJ-1. Reason: Overly specific downstream neuronal phenotype based on ortholog data. Not a well-characterized direct function of human DJ-1. |
| GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DJ-1 protects against ER stress-induced apoptosis (PMID:14652021). Consistent with experimental IGI evidence from the same PMID. Downstream protective effect. Reason: ER stress protection is a downstream consequence of DJ-1's general anti-apoptotic function, not a core molecular function. |
| GO:1902958 positive regulation of mitochondrial electron transport, NADH to ubiquinone | IEA GO_REF:0000107 | ACCEPT | Summary: DJ-1 binds mitochondrial complex I and maintains its activity (PMID:19822128). Complex I catalyzes NADH to ubiquinone electron transfer. Supported by IMP evidence. Reason: Consistent with IMP evidence from PMID:19822128 showing DJ-1 maintains complex I activity. |
| GO:1903189 glyoxal metabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation redundant with IBA. Glyoxal metabolism is a core enzymatic function of DJ-1 (PMID:22523093). Reason: Redundant with IBA but correct. Core glyoxalase function. |
| GO:1903377 negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DJ-1 protects neurons from oxidative stress-induced apoptosis (PMID:15790595, PMID:16632486, PMID:15983381). Consistent with experimental evidence. Reason: Neuron-specific anti-apoptotic effect is a downstream consequence of DJ-1's core oxidative stress response function. |
| GO:1903384 negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DJ-1 protects neurons from H2O2-induced apoptosis (PMID:14652021, PMID:24947010). Highly specific downstream term. Reason: Overly specific downstream protective phenotype. The core function is oxidative stress response. |
| GO:1903427 negative regulation of reactive oxygen species biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DJ-1 negatively regulates ROS production. This is consistent with its role in oxidative stress defense via Nrf2 stabilization and antioxidant gene regulation. Also supported by ISS evidence (GO_REF:0000024). Reason: Regulation of ROS biosynthesis is a downstream effect of DJ-1's antioxidant functions, not a direct molecular function. |
| GO:1903751 negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DJ-1 protects against H2O2-induced intrinsic apoptosis. Consistent with IDA evidence (PMID:24947010). Downstream protective effect. Reason: Highly specific downstream anti-apoptotic phenotype. Not a core molecular function. |
| GO:0036524 protein deglycase activity | IDA PMID:28596309 Guanine glycation repair by DJ-1/Park7 and its bacterial hom... | UNDECIDED | Summary: Richarme et al. reported DJ-1 acts as a nucleotide deglycase repairing guanine glycation (PMID:28596309). However, the deglycase activity is highly controversial. Andreeva et al. demonstrated that apparent deglycase activity results from glyoxalase-mediated removal of free methylglyoxal shifting equilibrium with hemithioacetals (PMID:31653696). Pfaff et al. also found no evidence for deglycase activity in Drosophila (PMID:27903648). Reason: The protein deglycase activity is the most controversial annotation for DJ-1. Strong evidence exists both for (Richarme group) and against (Andreeva, Pfaff). The field has not reached consensus. Glyoxalase activity may explain apparent deglycase results. Supporting Evidence: PMID:28596309 DJ-1 and its prokaryotic homologs constitute a major nucleotide repair system that we name guanine glycation repair PMID:31653696 our results suggest that DJ-1 does not possess protein deglycase activity |
| GO:0005634 nucleus | IPI PMID:12612053 DJBP: a novel DJ-1-binding protein, negatively regulates the... | ACCEPT | Summary: Nuclear localization of DJ-1 demonstrated in context of DJBP interaction and androgen receptor signaling (PMID:12612053). Reason: Nuclear localization confirmed by multiple independent studies. |
| GO:0030521 androgen receptor signaling pathway | NAS PMID:12612053 DJBP: a novel DJ-1-binding protein, negatively regulates the... | KEEP AS NON CORE | Summary: DJ-1 antagonizes DJBP-mediated inhibition of androgen receptor by abrogating HDAC complex recruitment (PMID:12612053). DJ-1 is a positive regulator of androgen receptor signaling. Reason: Androgen receptor signaling is a genuine DJ-1 function (supported by multiple studies) but represents a secondary role, possibly related to male fertility rather than core neuroprotective function. |
| GO:0033574 response to testosterone | NAS PMID:12612053 DJBP: a novel DJ-1-binding protein, negatively regulates the... | KEEP AS NON CORE | Summary: DJ-1 participates in androgen receptor signaling which is testosterone-responsive (PMID:12612053, PMID:17510388). NAS evidence. Reason: Response to testosterone is secondary to DJ-1's role in androgen receptor signaling. Not a core function. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Nucleoplasmic localization of DJ-1 determined by curation of immunofluorescence data. Consistent with nuclear localization from multiple studies. Reason: Nucleoplasm localization is a more specific version of nucleus annotation and is well-supported. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosolic localization of DJ-1 determined by curation of immunofluorescence data. DJ-1 is primarily cytosolic. Reason: Cytosol is the primary localization of DJ-1. Well-established. |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IMP PMID:22492997 DJ-1 induces thioredoxin 1 expression through the Nrf2 pathw... | KEEP AS NON CORE | Summary: DJ-1 induces thioredoxin 1 expression through the Nrf2 pathway, which involves PI3K/Akt signaling (PMID:22492997). This is a downstream signaling effect. Reason: PI3K/Akt regulation is a downstream signaling consequence of DJ-1's Nrf2-related transcriptional activity, not a core molecular function. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: DJ-1 identified in quantitative high-confidence human mitochondrial proteome (PMID:34800366). Consistent with extensive IDA evidence for mitochondrial localization. Reason: HTP confirmation of well-established mitochondrial localization. |
| GO:0036524 protein deglycase activity | IDA PMID:25416785 Parkinsonism-associated protein DJ-1/Park7 is a major protei... | UNDECIDED | Summary: Richarme et al. reported DJ-1 as a major protein deglycase repairing methylglyoxal- and glyoxal-glycated cysteine, arginine, and lysine residues (PMID:25416785). This claim is contested by subsequent work showing apparent deglycase activity may result from glyoxalase-mediated equilibrium shifts (PMID:31653696). Reason: Controversial. The original IDA evidence is from the Richarme group who reported strong deglycase activity, but this has been challenged by Andreeva et al. who showed DJ-1 does not possess true deglycase activity. Supporting Evidence: PMID:25416785 human DJ-1 is a protein deglycase that repairs methylglyoxal- and glyoxal-glycated amino acids and proteins by acting on early glycation intermediates and releases repaired proteins and lactate or glycolate PMID:31653696 removal of free MGO by DJ-1's glyoxalase activity forces immediate spontaneous decomposition of hemithioacetals due to the shift in equilibrium position |
| GO:0036524 protein deglycase activity | IMP PMID:26995087 The Parkinsonism-associated protein DJ-1/Park7 prevents glyc... | UNDECIDED | Summary: Advedissian et al. showed DJ-1 prevents glycation damage in human keratinocytes (PMID:26995087). The in vivo protection from glycation damage is real, but may be due to glyoxalase activity rather than true deglycase activity. Reason: Controversial. Protection from glycation is established, but the mechanism (deglycase vs glyoxalase) is debated. |
| GO:0036524 protein deglycase activity | IMP PMID:30150385 Methylglyoxal-derived posttranslational arginine modificatio... | UNDECIDED | Summary: DJ-1 protects histones from methylglyoxal adduction and controls levels of methylglyoxal-derived arginine modifications on chromatin (PMID:30150385). The protection from histone glycation is established but may reflect glyoxalase activity clearing free methylglyoxal rather than direct deglycase activity. Reason: Controversial. Histone glycation protection is demonstrated, but the underlying mechanism (deglycase vs glyoxalase) remains debated. |
| GO:0036524 protein deglycase activity | IMP PMID:30894531 Reversible histone glycation is associated with disease-rela... | UNDECIDED | Summary: DJ-1 shown to remove glycations and restore histone function (PMID:30894531). Histone glycation disrupts chromatin architecture. However, the deglycase vs glyoxalase mechanism debate applies here as well. Reason: Controversial. Same deglycase vs glyoxalase debate as other deglycase annotations. |
| GO:0008047 enzyme activator activity | IDA PMID:23743200 DJ-1 cooperates with PYCR1 in cell protection against oxidat... | ACCEPT | Summary: DJ-1 cooperates with PYCR1 in cell protection against oxidative stress (PMID:23743200). DJ-1 activates PYCR1 enzymatic activity. This is a specific interaction. Reason: Enzyme activator activity is supported by direct demonstration of DJ-1 activating PYCR1. |
| GO:0016532 superoxide dismutase copper chaperone activity | IDA PMID:24567322 DJ-1 is a copper chaperone acting on SOD1 activation. | ACCEPT | Summary: Girotto et al. demonstrated DJ-1 acts as a copper chaperone for SOD1 activation, transferring copper to SOD1 via a Cys-106-dependent binding site (PMID:24567322). This is a well-characterized core function. Reason: SOD1 copper chaperone activity is a core molecular function of DJ-1, demonstrated with structural and biochemical evidence. Supporting Evidence: PMID:24567322 The structural and functional analysis of the novel DJ-1 copper binding site led us to identify a putative role for DJ-1 as a copper chaperone |
| GO:0019430 removal of superoxide radicals | IDA PMID:24567322 DJ-1 is a copper chaperone acting on SOD1 activation. | KEEP AS NON CORE | Summary: DJ-1 contributes to superoxide removal indirectly by activating SOD1 via copper chaperoning (PMID:24567322). The removal of superoxide is a downstream effect of SOD1 activation. Reason: Superoxide removal is an indirect consequence of DJ-1's copper chaperone function for SOD1, not a direct enzymatic activity of DJ-1 itself. |
| GO:0030091 protein repair | IDA PMID:25416785 Parkinsonism-associated protein DJ-1/Park7 is a major protei... | UNDECIDED | Summary: Protein repair annotation based on Richarme et al.'s claim that DJ-1 repairs glycated proteins (PMID:25416785). This is contingent on the controversial deglycase activity. Reason: Protein repair depends on the disputed deglycase activity. If DJ-1 is a glyoxalase rather than deglycase, this annotation would be incorrect. |
| GO:0030414 peptidase inhibitor activity | IDA PMID:21097510 DJ-1 enhances cell survival through the binding of Cezanne, ... | KEEP AS NON CORE | Summary: DJ-1 reported to have peptidase inhibitor activity in context of NF-kappaB signaling study (PMID:21097510). DJ-1 inhibits the deubiquitinase OTUD7B/Cezanne. The term peptidase inhibitor activity may not be the most precise descriptor. Reason: The inhibition of OTUD7B deubiquitinase is real, but peptidase inhibitor activity is a somewhat imprecise description of this function. |
| GO:0030521 androgen receptor signaling pathway | IMP PMID:17510388 DJ-1 binds androgen receptor directly and mediates its activ... | KEEP AS NON CORE | Summary: DJ-1 directly binds androgen receptor and mediates its activity in hormonally treated prostate cancer cells (PMID:17510388). Experimental IMP evidence. Reason: Androgen receptor signaling is a validated DJ-1 function but not a core function in the context of neuroprotection. |
| GO:0030546 signaling receptor activator activity | IDA PMID:17510388 DJ-1 binds androgen receptor directly and mediates its activ... | KEEP AS NON CORE | Summary: DJ-1 directly binds and activates the androgen receptor (PMID:17510388). Signaling receptor activator activity is a broad term; the specific function is androgen receptor activation. Reason: The term is somewhat generic. The specific activity is androgen receptor coactivation, which is a non-core function. |
| GO:0031397 negative regulation of protein ubiquitination | IDA PMID:17015834 DJ-1, a cancer- and Parkinson's disease-associated protein, ... | ACCEPT | Summary: DJ-1 prevents Keap1-mediated ubiquitination of Nrf2, stabilizing the transcription factor (PMID:17015834). This is a key mechanism of DJ-1's antioxidant function. Reason: Core protective mechanism. DJ-1 stabilizes Nrf2 by preventing its ubiquitination by Keap1. Supporting Evidence: PMID:17015834 DJ-1 stabilizes Nrf2 by preventing association with its inhibitor protein, Keap1, and Nrf2's subsequent ubiquitination |
| GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process | IDA PMID:17015834 DJ-1, a cancer- and Parkinson's disease-associated protein, ... | ACCEPT | Summary: DJ-1 prevents proteasomal degradation of Nrf2 by blocking Keap1-mediated ubiquitination (PMID:17015834). Direct consequence of Nrf2 stabilization mechanism. Reason: Mechanistic extension of DJ-1's Nrf2 stabilization function. Well-supported. Supporting Evidence: PMID:17015834 Without intact DJ-1, Nrf2 protein is unstable, and transcriptional responses are thereby decreased both basally and after induction |
| GO:0032757 positive regulation of interleukin-8 production | IDA PMID:21097510 DJ-1 enhances cell survival through the binding of Cezanne, ... | KEEP AS NON CORE | Summary: DJ-1 enhances IL-8 production through NF-kappaB signaling via OTUD7B/Cezanne binding (PMID:21097510). This is a downstream inflammatory effect. Reason: IL-8 production regulation is a downstream effect of DJ-1's NF-kappaB modulation, not a core molecular function. |
| GO:0036470 tyrosine 3-monooxygenase activator activity | IDA PMID:19703902 Oxidative status of DJ-1-dependent activation of dopamine sy... | ACCEPT | Summary: DJ-1 activates tyrosine hydroxylase (TH) through direct interaction in a redox-dependent manner (PMID:19703902). TH is the rate-limiting enzyme in dopamine biosynthesis. Reason: TH activation is a specific and functionally important activity of DJ-1, directly relevant to dopamine biosynthesis and Parkinson disease. |
| GO:0036478 L-dopa decarboxylase activator activity | IDA PMID:19703902 Oxidative status of DJ-1-dependent activation of dopamine sy... | ACCEPT | Summary: DJ-1 activates L-DOPA decarboxylase (AADC) through direct interaction (PMID:19703902). AADC converts L-DOPA to dopamine. Reason: L-DOPA decarboxylase activation is a specific enzymatic activator function directly relevant to dopamine biosynthesis. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:16731528 DJ-1 transcriptionally up-regulates the human tyrosine hydro... | ACCEPT | Summary: DJ-1 transcriptionally up-regulates tyrosine hydroxylase by inhibiting sumoylation of PSF (PMID:16731528). DJ-1 acts as a transcriptional coactivator. Reason: Transcriptional coactivation is a core function of DJ-1, directly demonstrated here for TH gene regulation. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IGI PMID:17015834 DJ-1, a cancer- and Parkinson's disease-associated protein, ... | ACCEPT | Summary: DJ-1 positively regulates Nrf2-dependent transcription. Loss of DJ-1 leads to decreased Nrf2 transcriptional responses (PMID:17015834). Reason: Core function. DJ-1 stabilizes Nrf2 leading to enhanced Nrf2-dependent transcription. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:19703902 Oxidative status of DJ-1-dependent activation of dopamine sy... | ACCEPT | Summary: DJ-1 positively regulates transcription of dopamine biosynthetic genes through activation of TH and AADC (PMID:19703902). Reason: Transcriptional regulation of dopamine biosynthesis genes confirmed by IMP evidence. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:21097510 DJ-1 enhances cell survival through the binding of Cezanne, ... | ACCEPT | Summary: DJ-1 enhances NF-kappaB-dependent transcription through binding of OTUD7B/Cezanne (PMID:21097510). Reason: Transcriptional coactivation via NF-kappaB pathway demonstrated with IDA evidence. |
| GO:0046826 negative regulation of protein export from nucleus | IGI PMID:15983381 Interaction of DJ-1 with Daxx inhibits apoptosis signal-regu... | KEEP AS NON CORE | Summary: DJ-1 interaction with Daxx prevents nuclear export of Daxx, sequestering it in the nucleus and preventing ASK1 activation (PMID:15983381). Specific mechanism of anti-apoptotic activity. Reason: Preventing Daxx nuclear export is a specific mechanism in the Daxx-ASK1 apoptotic signaling pathway. It is downstream of DJ-1's general protective function. |
| GO:0050681 nuclear androgen receptor binding | IPI PMID:17510388 DJ-1 binds androgen receptor directly and mediates its activ... | KEEP AS NON CORE | Summary: DJ-1 directly binds the androgen receptor in the nucleus and mediates its transcriptional activity (PMID:17510388). Specific molecular function term. Reason: Nuclear androgen receptor binding is a specific and validated molecular function, but it represents a secondary role of DJ-1 related to male fertility/prostate biology rather than core neuroprotective function. |
| GO:0050821 protein stabilization | IMP PMID:17015834 DJ-1, a cancer- and Parkinson's disease-associated protein, ... | ACCEPT | Summary: DJ-1 stabilizes Nrf2 protein by preventing Keap1-mediated ubiquitination and proteasomal degradation (PMID:17015834). Core protective mechanism. Reason: Nrf2 protein stabilization is one of the best-characterized protective functions of DJ-1. Supporting Evidence: PMID:17015834 DJ-1 stabilizes Nrf2 by preventing association with its inhibitor protein, Keap1, and Nrf2's subsequent ubiquitination |
| GO:0055105 ubiquitin-protein transferase inhibitor activity | IDA PMID:24899725 Regulation of the VHL/HIF-1 pathway by DJ-1. | ACCEPT | Summary: DJ-1 inhibits VHL ubiquitin E3 ligase activity, regulating the VHL/HIF-1 pathway (PMID:24899725). Specific molecular function. Reason: Ubiquitin-protein transferase inhibitor activity is a specific molecular function consistent with DJ-1's role in preventing ubiquitination of targets like Nrf2 and HIF-1alpha. |
| GO:1900182 positive regulation of protein localization to nucleus | IMP PMID:22492997 DJ-1 induces thioredoxin 1 expression through the Nrf2 pathw... | KEEP AS NON CORE | Summary: DJ-1 promotes nuclear localization of Nrf2 through the PI3K/Akt pathway, inducing thioredoxin 1 expression (PMID:22492997). Reason: Promoting Nrf2 nuclear localization is a downstream effect of DJ-1's Nrf2 stabilization function. |
| GO:1903073 negative regulation of death-inducing signaling complex assembly | IMP PMID:21785459 DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspas... | KEEP AS NON CORE | Summary: DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspase-8 recruitment to FADD, preventing DISC assembly (PMID:21785459). Specific anti-apoptotic mechanism. Reason: DISC assembly regulation is a specific anti-apoptotic mechanism, downstream of DJ-1's general protective role. |
| GO:1903181 positive regulation of dopamine biosynthetic process | IC PMID:16731528 DJ-1 transcriptionally up-regulates the human tyrosine hydro... | ACCEPT | Summary: DJ-1 up-regulates TH transcription by inhibiting PSF sumoylation, leading to increased dopamine biosynthesis (PMID:16731528). Inferred from curator reasoning (IC). Reason: Positive regulation of dopamine biosynthesis is a key function relevant to Parkinson disease pathology, logically following from TH transcriptional upregulation. |
| GO:1903197 positive regulation of L-dopa biosynthetic process | IMP PMID:16731528 DJ-1 transcriptionally up-regulates the human tyrosine hydro... | ACCEPT | Summary: DJ-1 promotes L-DOPA biosynthesis through TH transcriptional upregulation (PMID:16731528). L-DOPA is the product of TH activity. Reason: L-DOPA biosynthesis regulation directly follows from DJ-1's TH activation function. Relevant to Parkinson disease. |
| GO:0005634 nucleus | IDA PMID:22683601 Nuclear translocation of DJ-1 during oxidative stress-induce... | ACCEPT | Summary: Nuclear translocation of DJ-1 demonstrated during oxidative stress-induced neuronal cell death (PMID:22683601). IDA evidence. Reason: Nuclear localization confirmed by direct observation during oxidative stress. |
| GO:0043524 negative regulation of neuron apoptotic process | IDA PMID:22683601 Nuclear translocation of DJ-1 during oxidative stress-induce... | KEEP AS NON CORE | Summary: DJ-1 protects neurons from apoptosis during oxidative stress (PMID:22683601). Well-established neuroprotective role. Reason: Anti-apoptotic effect in neurons is a downstream consequence of DJ-1's core oxidative stress response function. |
| GO:0005515 protein binding | IPI PMID:20969476 DJ-1 cleavage by matrix metalloproteinase 3 mediates oxidati... | MARK AS OVER ANNOTATED | Summary: DJ-1 identified as substrate of matrix metalloproteinase 3 (MMP3) cleavage (PMID:20969476). Generic protein binding. Reason: Generic protein binding is uninformative. DJ-1 cleavage by MMP3 is a specific observation but protein binding does not capture the relevant biology. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:22492997 DJ-1 induces thioredoxin 1 expression through the Nrf2 pathw... | ACCEPT | Summary: DJ-1 induces thioredoxin 1 expression through Nrf2-dependent transcription (PMID:22492997). Positive transcriptional regulation confirmed by IMP evidence. Reason: Consistent with DJ-1's role as transcriptional coactivator via Nrf2 pathway. |
| GO:0070301 cellular response to hydrogen peroxide | IMP PMID:22492997 DJ-1 induces thioredoxin 1 expression through the Nrf2 pathw... | ACCEPT | Summary: DJ-1 responds to H2O2 by activating Nrf2-dependent thioredoxin 1 transcription (PMID:22492997). Cellular H2O2 response is part of oxidative stress defense. Reason: Response to H2O2 is a specific aspect of DJ-1's core oxidative stress response function. |
| GO:1903376 regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway | IDA PMID:15983381 Interaction of DJ-1 with Daxx inhibits apoptosis signal-regu... | KEEP AS NON CORE | Summary: DJ-1 regulates oxidative stress-induced neuron apoptosis through Daxx-ASK1 pathway (PMID:15983381). Interaction with Daxx sequesters it in nucleus. Reason: Neuron-specific apoptosis regulation is downstream of DJ-1's core oxidative stress response function. |
| GO:1903377 negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway | IDA PMID:16632486 Association of PINK1 and DJ-1 confers digenic inheritance of... | KEEP AS NON CORE | Summary: DJ-1 protects neurons from oxidative stress-induced apoptosis, demonstrated in context of PINK1 association study (PMID:16632486). Reason: Downstream neuroprotective phenotype. The more general anti-apoptotic protective function is core. |
| GO:2000379 positive regulation of reactive oxygen species metabolic process | IDA PMID:20969476 DJ-1 cleavage by matrix metalloproteinase 3 mediates oxidati... | MARK AS OVER ANNOTATED | Summary: DJ-1 cleavage by MMP3 mediates oxidative stress-induced dopaminergic cell death, leading to ROS accumulation (PMID:20969476). This describes a pathological consequence when DJ-1 is cleaved, not a normal DJ-1 function. Reason: This annotation describes the pathological consequence of DJ-1 cleavage by MMP3 leading to ROS increase, not a normal physiological function of DJ-1. DJ-1 normally suppresses ROS. |
| GO:1903377 negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway | IMP PMID:23743200 DJ-1 cooperates with PYCR1 in cell protection against oxidat... | KEEP AS NON CORE | Summary: DJ-1 cooperates with PYCR1 to protect neurons from oxidative stress-induced apoptosis (PMID:23743200). Reason: Downstream neuroprotective phenotype. Overly specific term for what is a general anti-apoptotic function. |
| GO:1903751 negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide | IDA PMID:24947010 DJ-1 interacts with RACK1 and protects neurons from oxidativ... | KEEP AS NON CORE | Summary: DJ-1 interacts with RACK1 to protect neurons from H2O2-induced apoptosis (PMID:24947010). Highly specific term. Reason: Overly specific downstream protective phenotype. |
| GO:0042803 protein homodimerization activity | IPI PMID:24144264 Structure of Cu(I)-bound DJ-1 reveals a biscysteinate metal ... | ACCEPT | Summary: DJ-1 homodimerization confirmed by structural study of Cu(I)-bound DJ-1 showing biscysteinate metal binding site at the homodimer interface (PMID:24144264). Reason: Homodimerization is essential for DJ-1 function. Well-established by structural and biochemical evidence. Supporting Evidence: PMID:24144264 Structure of Cu(I)-bound DJ-1 reveals a biscysteinate metal binding site at the homodimer interface |
| GO:0042803 protein homodimerization activity | IPI PMID:24567322 DJ-1 is a copper chaperone acting on SOD1 activation. | ACCEPT | Summary: DJ-1 homodimerization confirmed in context of copper chaperone study (PMID:24567322). The copper binding site involves Cys-106 at the dimer interface. Reason: Homodimerization is essential for DJ-1 function. Confirmed by multiple independent studies. |
| GO:1902176 negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway | IDA PMID:22523093 Human DJ-1 and its homologs are novel glyoxalases. | KEEP AS NON CORE | Summary: DJ-1 glyoxalase activity protects cells from glyoxal/methylglyoxal-induced oxidative stress and apoptosis (PMID:22523093). Reason: Downstream protective phenotype resulting from glyoxalase activity and oxidative stress defense. |
| GO:0061691 detoxification of hydrogen peroxide | IDA PMID:14749723 DJ-1 has a role in antioxidative stress to prevent cell deat... | ACCEPT | Summary: Taira et al. demonstrated DJ-1 has a role in antioxidative stress and can eliminate hydrogen peroxide (PMID:14749723). The H2O2 detoxification is Cys-106 dependent. Reason: H2O2 detoxification is a core redox function of DJ-1, supported by direct experimental evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-4085331 | ACCEPT | Summary: Reactome pathway annotation for PIAS2-1 SUMOylation of PARK7 with SUMO1. DJ-1 is sumoylated in the nucleoplasm. Consistent with known nuclear localization and SUMO modification. Reason: Nucleoplasmic localization consistent with known sumoylation at Lys-130 by PIAS2 and nuclear functions. |
| GO:0032679 regulation of TRAIL production | IMP NOT PMID:21785459 DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspas... | ACCEPT | Summary: NOT annotation - DJ-1 does NOT regulate TRAIL production (PMID:21785459). DJ-1 inhibits TRAIL-induced apoptosis by blocking DISC assembly, not by affecting TRAIL levels. Reason: Negated annotation correctly distinguishes that DJ-1 inhibits TRAIL signaling downstream (at DISC assembly), not TRAIL production itself. |
| GO:0050821 protein stabilization | IDA PMID:24947010 DJ-1 interacts with RACK1 and protects neurons from oxidativ... | ACCEPT | Summary: DJ-1 stabilizes RACK1 protein, protecting neurons from oxidative stress-induced apoptosis (PMID:24947010). Reason: Protein stabilization is a general mechanism by which DJ-1 exerts protective effects, consistent with Nrf2 and PINK1 stabilization. |
| GO:0005102 signaling receptor binding | IPI PMID:21785459 DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspas... | KEEP AS NON CORE | Summary: DJ-1 binds FADD (death receptor signaling component) to block TRAIL-induced apoptosis (PMID:21785459). Signaling receptor binding is somewhat imprecise for this interaction. Reason: FADD interaction is specific to TRAIL apoptotic signaling. Signaling receptor binding is a broad term for this specific anti-apoptotic mechanism. |
| GO:0036524 protein deglycase activity | IDA NOT PMID:31653696 The apparent deglycase activity of DJ-1 results from the con... | ACCEPT | Summary: NOT annotation - Andreeva et al. demonstrated DJ-1 does NOT possess protein deglycase activity. Apparent deglycase activity results from conversion of free methylglyoxal in fast equilibrium with hemithioacetals, not direct deglycation (PMID:31653696). Reason: Important negated annotation documenting that DJ-1 lacks true deglycase activity. Critical for resolving the deglycase controversy. Supporting Evidence: PMID:31653696 our results suggest that DJ-1 does not possess protein deglycase activity |
| GO:0110095 cellular detoxification of aldehyde | IDA PMID:28993701 Parkinson's disease-related DJ-1 functions in thiol quality ... | ACCEPT | Summary: DJ-1 functions in thiol quality control against aldehyde attack in vitro (PMID:28993701). Aldehyde detoxification is related to glyoxalase function. Reason: Aldehyde detoxification is consistent with DJ-1's glyoxalase activity against reactive carbonyl species. |
| GO:0140041 cellular detoxification of methylglyoxal | IDA PMID:28993701 Parkinson's disease-related DJ-1 functions in thiol quality ... | ACCEPT | Summary: DJ-1 detoxifies methylglyoxal through its glyoxalase activity (PMID:28993701, PMID:22523093). Core enzymatic function. Reason: Methylglyoxal detoxification is a core enzymatic activity of DJ-1, well-established by multiple studies. |
| GO:1990422 glyoxalase (glycolic acid-forming) activity | IDA PMID:31653696 The apparent deglycase activity of DJ-1 results from the con... | ACCEPT | Summary: Andreeva et al. confirmed DJ-1 has glyoxalase activity forming glycolic acid from glyoxal (PMID:31653696). This is the activity that explains apparent deglycase results. Reason: Glyoxalase activity is the best-established enzymatic function of DJ-1, confirmed even by groups that dispute deglycase activity. Supporting Evidence: PMID:31653696 DJ-1 has been suggested to be a GSH-independent glyoxalase that detoxifies methylglyoxal (MGO) by converting it into lactate |
| GO:0005515 protein binding | IPI PMID:31536960 Rewiring of the Human Mitochondrial Interactome during Neuro... | MARK AS OVER ANNOTATED | Summary: DJ-1 identified in human mitochondrial interactome during neuronal reprogramming (PMID:31536960). High-throughput interactome study. Reason: Generic protein binding from high-throughput mitochondrial interactome study. |
| GO:0005739 mitochondrion | IDA PMID:31536960 Rewiring of the Human Mitochondrial Interactome during Neuro... | ACCEPT | Summary: Mitochondrial localization confirmed in human mitochondrial interactome study (PMID:31536960). Consistent with extensive prior evidence. Reason: Additional IDA confirmation of well-established mitochondrial localization. |
| GO:0005783 endoplasmic reticulum | IDA PMID:31536960 Rewiring of the Human Mitochondrial Interactome during Neuro... | ACCEPT | Summary: ER localization detected in mitochondrial interactome study (PMID:31536960). Consistent with DJ-1's role in ER stress protection. Reason: ER localization supported by IDA evidence. Consistent with DJ-1's role in ER stress-induced apoptotic signaling. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9641096 | ACCEPT | Summary: Reactome pathway annotation for misfolded proteins binding PRKN complex. DJ-1 participates in PINK1-Parkin pathway in cytosol. Reason: Cytosolic localization for PINK1-Parkin-DJ-1 pathway activity is well-established. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9641109 | ACCEPT | Summary: Reactome pathway annotation for polyUb-misfolded protein dissociation from PRKN complex. Reason: Cytosolic localization for Parkin pathway is well-established. Redundant but correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9641111 | ACCEPT | Summary: Reactome pathway annotation for Parkin ubiquitin transfer to misfolded proteins. Reason: Cytosolic localization for Parkin pathway is well-established. Redundant but correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9641127 | ACCEPT | Summary: Reactome pathway annotation for ubiquitin polymerization on misfolded proteins. Reason: Cytosolic localization for Parkin pathway is well-established. Redundant but correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9646348 | ACCEPT | Summary: Reactome pathway annotation for polyUb-misfolded proteins binding HDAC6-dynein motor. Reason: Cytosolic localization for aggresome pathway is well-established. Redundant but correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9646679 | ACCEPT | Summary: Reactome pathway annotation for aggresome formation with vimentin. Reason: Cytosolic localization for aggresome pathway is well-established. Redundant but correct. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9646685 | ACCEPT | Summary: Reactome pathway annotation for aggresome dissociation from dynein and microtubule. Reason: Cytosolic localization for aggresome pathway is well-established. Redundant but correct. |
| GO:0031334 positive regulation of protein-containing complex assembly | IDA PMID:24947010 DJ-1 interacts with RACK1 and protects neurons from oxidativ... | KEEP AS NON CORE | Summary: DJ-1 promotes assembly of protective protein complexes, demonstrated in context of RACK1 interaction study (PMID:24947010). Reason: Complex assembly regulation is a downstream mechanism of DJ-1's protective function, not a core molecular function. |
| GO:0005515 protein binding | IPI PMID:19822128 DJ-1 binds to mitochondrial complex I and maintains its acti... | MARK AS OVER ANNOTATED | Summary: DJ-1 binds mitochondrial complex I components (PMID:19822128). More specific enzyme binding (GO:0019899) is annotated separately. Reason: Generic protein binding is redundant with more specific enzyme binding annotation from the same reference. |
| GO:0045296 cadherin binding | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | MARK AS OVER ANNOTATED | Summary: DJ-1 identified in E-cadherin interactome by quantitative proteomics (PMID:25468996). High-throughput finding of uncertain functional relevance to DJ-1. Reason: Cadherin binding from high-throughput proteomics is likely not a core function of DJ-1 and may represent a non-specific interaction. |
| GO:0005912 adherens junction | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | MARK AS OVER ANNOTATED | Summary: DJ-1 localized to adherens junctions by high-throughput proteomics of E-cadherin interactome (PMID:25468996). Likely non-specific finding. Reason: Adherens junction localization from HDA proteomics study is unlikely to represent a functionally important localization for DJ-1. |
| GO:0006281 DNA repair | IDA PMID:28596309 Guanine glycation repair by DJ-1/Park7 and its bacterial hom... | UNDECIDED | Summary: Richarme et al. reported DJ-1 repairs glycated guanine in DNA (PMID:28596309). This is contingent on the controversial nucleotide deglycase activity. Reason: DNA repair via nucleotide deglycase activity is from the Richarme group whose deglycase claims are disputed. The underlying mechanism (deglycase vs glyoxalase equilibrium shift) is unresolved. |
| GO:0030073 insulin secretion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation transferred from mouse data showing DJ-1 role in pancreatic islet function (PMID:22611253). Secondary tissue-specific phenotype. Reason: Insulin secretion role is from mouse ortholog transfer. Not a core molecular function. |
| GO:0042593 glucose homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation transferred from mouse. DJ-1 involved in glucose homeostasis in pancreatic islets in age/diet-dependent manner (PMID:22611253). Reason: Secondary metabolic phenotype from mouse ortholog. Not core molecular function. |
| GO:1903427 negative regulation of reactive oxygen species biosynthetic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation consistent with DJ-1's established role in suppressing ROS production through Nrf2 and antioxidant pathways. Reason: ROS biosynthesis regulation is a downstream effect of DJ-1's antioxidant functions. ISS evidence from ortholog. |
| GO:0002866 positive regulation of acute inflammatory response to antigenic stimulus | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS annotation from mouse data. DJ-1 modulates inflammatory responses but primarily acts as an anti-inflammatory factor. The positive regulation of acute inflammatory response is counterintuitive and may reflect a specific mouse phenotype. Reason: Similar to IEA annotation for same term. DJ-1 generally dampens inflammation. This overly specific term may be misleading about DJ-1's actual role. |
| GO:0009438 methylglyoxal metabolic process | IDA NOT PMID:27903648 Evidence Against a Role for the Parkinsonism-associated Prot... | ACCEPT | Summary: NOT annotation - Pfaff et al. found no evidence for DJ-1 involvement in methylglyoxal detoxification in Drosophila and attributed in vitro cysteine deglycase activity to a TRIS buffer artifact (PMID:27903648). Note this contradicts other studies showing DJ-1 glyoxalase activity. Reason: Important negated annotation. However, this may be specific to Drosophila context. Human DJ-1 glyoxalase activity is supported by other studies (PMID:22523093, PMID:31653696). The annotation correctly records the negative finding from this study. |
| GO:1990381 ubiquitin-specific protease binding | IPI PMID:21097510 DJ-1 enhances cell survival through the binding of Cezanne, ... | ACCEPT | Summary: DJ-1 binds OTUD7B/Cezanne, a deubiquitinating enzyme that negatively regulates NF-kappaB (PMID:21097510). Specific and informative molecular function term. Reason: Ubiquitin-specific protease binding is a specific and accurate MF term for DJ-1's interaction with OTUD7B/Cezanne. More informative than generic protein binding. |
| GO:0009438 methylglyoxal metabolic process | IDA PMID:22523093 Human DJ-1 and its homologs are novel glyoxalases. | ACCEPT | Summary: DJ-1 metabolizes methylglyoxal to lactate via GSH-independent glyoxalase activity (PMID:22523093). Core enzymatic function. Reason: Methylglyoxal metabolism is a core enzymatic activity directly demonstrated with purified DJ-1. Supporting Evidence: PMID:22523093 human DJ-1 and its homologs of the mouse and Caenorhabditis elegans are novel types of glyoxalase, converting glyoxal or methylglyoxal to glycolic or lactic acid, respectively |
| GO:0019249 lactate biosynthetic process | IDA PMID:22523093 Human DJ-1 and its homologs are novel glyoxalases. | ACCEPT | Summary: DJ-1 glyoxalase activity produces lactate from methylglyoxal (PMID:22523093). Direct product of glyoxalase reaction. Reason: Lactate production is the confirmed product of DJ-1's glyoxalase activity on methylglyoxal. |
| GO:1903189 glyoxal metabolic process | IDA PMID:22523093 Human DJ-1 and its homologs are novel glyoxalases. | ACCEPT | Summary: DJ-1 metabolizes glyoxal via glyoxalase activity (PMID:22523093). IDA evidence from Lee et al. Core enzymatic function. Reason: Direct experimental evidence for glyoxal metabolism by purified DJ-1. |
| GO:1905259 negative regulation of nitrosative stress-induced intrinsic apoptotic signaling pathway | IDA PMID:14752510 hsp70-DnaJ chaperone pair prevents nitric oxide- and CHOP-in... | KEEP AS NON CORE | Summary: DJ-1 protects against nitric oxide-induced apoptosis (PMID:14752510). Overly specific downstream protective phenotype. Reason: Anti-apoptotic effect against nitrosative stress is a specific protective phenotype, not a core molecular function. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | KEEP AS NON CORE | Summary: DJ-1 detected in perinuclear region in E-cadherin interactome study (PMID:25468996). HDA-derived finding. Reason: Perinuclear localization is a specific observation from a proteomics study, consistent with cytoplasmic/nuclear distribution but not a primary localization. |
| GO:0033234 negative regulation of protein sumoylation | IDA PMID:16731528 DJ-1 transcriptionally up-regulates the human tyrosine hydro... | ACCEPT | Summary: DJ-1 inhibits PSF sumoylation, leading to transcriptional upregulation of TH (PMID:16731528). Specific mechanism of transcriptional coactivation. Reason: Inhibition of PSF sumoylation is the specific molecular mechanism by which DJ-1 upregulates TH transcription. Well-characterized. |
| GO:0034599 cellular response to oxidative stress | IDA PMID:15983381 Interaction of DJ-1 with Daxx inhibits apoptosis signal-regu... | ACCEPT | Summary: DJ-1 responds to oxidative stress by interacting with Daxx to inhibit ASK1-mediated apoptosis (PMID:15983381). Core function. Reason: Cellular response to oxidative stress is a core function of DJ-1. IDA evidence from Daxx-ASK1 pathway study. |
| GO:1903599 positive regulation of autophagy of mitochondrion | NAS PMID:24531622 Glucocerebrosidase is shaking up the synucleinopathies. | KEEP AS NON CORE | Summary: DJ-1 promotes mitophagy as part of the PINK1-Parkin-DJ-1 mitochondrial quality control axis (PMID:24531622). NAS evidence from a review article on synucleinopathies. Reason: Mitophagy regulation is a downstream consequence of DJ-1's role in mitochondrial quality control. NAS evidence from a review article. |
| GO:0005507 copper ion binding | IDA PMID:23792957 Parkinson disease protein DJ-1 binds metals and protects aga... | ACCEPT | Summary: DJ-1 binds both Cu(I) and Cu(II) ions via Cys-106 (PMID:23792957, PMID:24144264, PMID:24567322). Core metal-binding function. Reason: Copper ion binding is a well-characterized molecular function of DJ-1, essential for its copper chaperone activity for SOD1. |
| GO:0010273 detoxification of copper ion | IMP PMID:23792957 Parkinson disease protein DJ-1 binds metals and protects aga... | ACCEPT | Summary: DJ-1 protects against copper-induced cytotoxicity (PMID:23792957). Metal detoxification supported by IMP evidence. Reason: Copper detoxification is experimentally demonstrated. DJ-1 binds copper and protects cells from copper toxicity. |
| GO:0045340 mercury ion binding | IDA PMID:23792957 Parkinson disease protein DJ-1 binds metals and protects aga... | KEEP AS NON CORE | Summary: DJ-1 binds mercury ions and protects against mercury-induced cytotoxicity (PMID:23792957). Direct IDA evidence. Reason: Mercury binding is experimentally validated but likely a secondary consequence of the general metal-binding capacity of DJ-1 rather than a core function. |
| GO:0005515 protein binding | IPI PMID:19229105 Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex p... | MARK AS OVER ANNOTATED | Summary: DJ-1 interacts with Parkin and PINK1 forming a ubiquitin E3 ligase complex (PMID:19229105). More specific kinase binding (GO:0019900) is annotated separately. Reason: Generic protein binding is redundant with more specific kinase binding annotation from the same reference. |
| GO:0005739 mitochondrion | IDA PMID:19229105 Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex p... | ACCEPT | Summary: Mitochondrial localization confirmed in PINK1-Parkin-DJ-1 complex study (PMID:19229105). Reason: Additional IDA confirmation of mitochondrial localization in functionally relevant context. |
| GO:0005829 cytosol | IDA PMID:19229105 Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex p... | ACCEPT | Summary: Cytosolic localization confirmed in PINK1-Parkin-DJ-1 complex study (PMID:19229105). Reason: Cytosolic localization well-established. |
| GO:0019900 kinase binding | IPI PMID:19229105 Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex p... | ACCEPT | Summary: DJ-1 binds PINK1 kinase as part of the PINK1-Parkin-DJ-1 complex (PMID:19229105). Specific and functionally relevant molecular function. Reason: PINK1 kinase binding is a specific and important interaction for DJ-1's role in mitochondrial quality control. |
| GO:0050821 protein stabilization | IMP PMID:19229105 Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex p... | ACCEPT | Summary: DJ-1 stabilizes PINK1 and Parkin proteins, promoting unfolded protein degradation (PMID:19229105). Reason: Protein stabilization of PINK1 is a key function consistent with DJ-1's role in mitochondrial quality control. |
| GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway | IGI PMID:14652021 Down regulation of DJ-1 enhances cell death by oxidative str... | KEEP AS NON CORE | Summary: Down-regulation of DJ-1 enhances cell death by ER stress (PMID:14652021). DJ-1 protects against ER stress-induced apoptosis. IGI evidence. Reason: ER stress protection is a downstream protective effect, not a core molecular function. |
| GO:1903384 negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway | IGI PMID:14652021 Down regulation of DJ-1 enhances cell death by oxidative str... | KEEP AS NON CORE | Summary: Down-regulation of DJ-1 enhances H2O2-induced neuronal apoptosis (PMID:14652021). IGI evidence. Reason: Downstream neuroprotective phenotype. Overly specific term. |
| GO:0005515 protein binding | IPI PMID:11477070 DJ-1 positively regulates the androgen receptor by impairing... | MARK AS OVER ANNOTATED | Summary: DJ-1 interacts with PIAS2 in the androgen receptor signaling pathway (PMID:11477070). Generic protein binding. Reason: Generic protein binding is uninformative. The specific interaction with PIAS2 is more relevant. |
| GO:0010628 positive regulation of gene expression | TAS PMID:24252804 The role of oxidative stress in Parkinson's disease. | ACCEPT | Summary: DJ-1 positively regulates gene expression through Nrf2 stabilization and transcriptional coactivation. TAS from review on oxidative stress in PD (PMID:24252804). Reason: Consistent with DJ-1's established role as transcriptional coactivator and Nrf2 stabilizer. |
| GO:0005634 nucleus | IDA PMID:14662519 The expression of DJ-1 (PARK7) in normal human CNS and idiop... | ACCEPT | Summary: Nuclear localization of DJ-1 in normal human CNS (PMID:14662519). Reason: Nuclear localization confirmed in human brain tissue. |
| GO:0005829 cytosol | IDA PMID:14662519 The expression of DJ-1 (PARK7) in normal human CNS and idiop... | ACCEPT | Summary: Cytosolic localization of DJ-1 in normal human CNS (PMID:14662519). Reason: Cytosolic localization confirmed in human brain tissue. |
| GO:0007265 Ras protein signal transduction | TAS PMID:14662519 The expression of DJ-1 (PARK7) in normal human CNS and idiop... | KEEP AS NON CORE | Summary: DJ-1 was originally identified as an oncogene that transforms NIH3T3 cells in cooperation with ras (PMID:9070310). Ras signaling involvement is from this original oncogene characterization. Reason: Ras signaling involvement relates to DJ-1's original identification as an oncogene (DJ1). This is a secondary role, not a core molecular function in the context of neuroprotection. |
| GO:0030424 axon | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Axonal localization transferred from ortholog data. Plausible given neuronal expression and Parkinson disease relevance. Reason: Axonal localization from ortholog transfer. Not specifically validated in human. |
| GO:1902903 regulation of supramolecular fiber organization | TAS PMID:23626584 Structure and Function of Parkin, PINK1, and DJ-1, the Three... | KEEP AS NON CORE | Summary: DJ-1 regulates cytoskeletal organization as reviewed in context of PINK1-Parkin-DJ-1 neuroprotection (PMID:23626584). TAS from review article. Reason: Supramolecular fiber organization regulation is a broad downstream effect. Not a core molecular function. |
| GO:0036471 cellular response to glyoxal | IDA PMID:22523093 Human DJ-1 and its homologs are novel glyoxalases. | ACCEPT | Summary: DJ-1 responds to glyoxal by metabolizing it via glyoxalase activity (PMID:22523093). Core enzymatic response. Reason: Glyoxal response is directly linked to DJ-1's core glyoxalase function. |
| GO:1903377 negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway | IDA PMID:15790595 The Parkinson's disease-associated DJ-1 protein is a transcr... | KEEP AS NON CORE | Summary: DJ-1 acts as a transcriptional co-activator that protects against neuronal apoptosis (PMID:15790595). Neuroprotective function. Reason: Downstream neuroprotective phenotype. Core function is transcriptional coactivation and oxidative stress response. |
| GO:0005515 protein binding | IPI PMID:16632486 Association of PINK1 and DJ-1 confers digenic inheritance of... | MARK AS OVER ANNOTATED | Summary: DJ-1 interacts with PINK1 (PMID:16632486). PINK1 interaction is functionally important but generic protein binding is uninformative. Reason: Generic protein binding is uninformative. The PINK1 interaction is more specifically captured by kinase binding annotation. |
| GO:0003713 transcription coactivator activity | IGI PMID:15790595 The Parkinson's disease-associated DJ-1 protein is a transcr... | ACCEPT | Summary: DJ-1 functions as a transcriptional co-activator, demonstrated in context of neuroprotection (PMID:15790595). Core molecular function. Reason: Transcription coactivator activity is a well-established core molecular function of DJ-1. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IGI PMID:15790595 The Parkinson's disease-associated DJ-1 protein is a transcr... | ACCEPT | Summary: DJ-1 positively regulates transcription as a transcriptional co-activator (PMID:15790595). IGI evidence. Reason: Positive transcriptional regulation is a well-supported process annotation for DJ-1. |
| GO:0000785 chromatin | IDA PMID:16731528 DJ-1 transcriptionally up-regulates the human tyrosine hydro... | ACCEPT | Summary: DJ-1 associates with chromatin in context of TH transcriptional regulation via PSF sumoylation inhibition (PMID:16731528). Reason: Chromatin association is consistent with DJ-1's role as transcriptional coactivator. |
| GO:0001046 core promoter sequence-specific DNA binding | IC NOT PMID:15790595 The Parkinson's disease-associated DJ-1 protein is a transcr... | ACCEPT | Summary: NOT annotation - DJ-1 does NOT bind DNA directly at core promoter sequences (PMID:15790595). DJ-1 functions as a transcriptional coactivator through protein-protein interactions rather than direct DNA binding. Reason: Important negated annotation clarifying that DJ-1's transcriptional coactivation does not involve direct DNA binding. |
| GO:0005739 mitochondrion | IDA PMID:15790595 The Parkinson's disease-associated DJ-1 protein is a transcr... | ACCEPT | Summary: Mitochondrial localization of DJ-1 confirmed in transcriptional co-activator study (PMID:15790595). Reason: Additional IDA confirmation of mitochondrial localization. |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:15790595 The Parkinson's disease-associated DJ-1 protein is a transcr... | ACCEPT | Summary: DJ-1 binds transcription factors as part of its coactivator function (PMID:15790595). Specific and informative MF term. Reason: DNA-binding transcription factor binding is a specific molecular function consistent with DJ-1's transcriptional coactivator role. |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:16731528 DJ-1 transcriptionally up-regulates the human tyrosine hydro... | ACCEPT | Summary: DJ-1 binds PSF transcription factor, inhibiting its sumoylation (PMID:16731528). Specific MF term. Reason: Specific molecular function term for DJ-1's interaction with PSF in TH transcriptional regulation. |
| GO:0005515 protein binding | IPI PMID:15790595 The Parkinson's disease-associated DJ-1 protein is a transcr... | MARK AS OVER ANNOTATED | Summary: DJ-1 binds p54nrb/PSF transcription factors (PMID:15790595). More specific DNA-binding transcription factor binding (GO:0140297) is annotated separately. Reason: Generic protein binding is redundant with more specific GO:0140297 annotation from the same reference. |
| GO:0005634 nucleus | IDA PMID:15790595 The Parkinson's disease-associated DJ-1 protein is a transcr... | ACCEPT | Summary: Nuclear localization of DJ-1 confirmed in transcriptional co-activator study (PMID:15790595). Reason: Well-established nuclear localization. |
| GO:0005634 nucleus | IDA PMID:19822128 DJ-1 binds to mitochondrial complex I and maintains its acti... | ACCEPT | Summary: Nuclear localization confirmed in complex I study (PMID:19822128). Reason: Well-established nuclear localization. |
| GO:0005737 cytoplasm | IDA PMID:19822128 DJ-1 binds to mitochondrial complex I and maintains its acti... | ACCEPT | Summary: Cytoplasmic localization confirmed in complex I study (PMID:19822128). Reason: Well-established cytoplasmic localization. |
| GO:0005739 mitochondrion | IDA PMID:19822128 DJ-1 binds to mitochondrial complex I and maintains its acti... | ACCEPT | Summary: Mitochondrial localization confirmed in complex I binding study (PMID:19822128). DJ-1 binds mitochondrial complex I directly. Reason: Mitochondrial localization is central to DJ-1's complex I maintenance function. |
| GO:0019899 enzyme binding | IPI PMID:19822128 DJ-1 binds to mitochondrial complex I and maintains its acti... | ACCEPT | Summary: DJ-1 binds mitochondrial complex I subunits (PMID:19822128). Enzyme binding is a specific and informative term for this interaction. Reason: Complex I enzyme binding is a specific molecular function relevant to DJ-1's mitochondrial protective role. |
| GO:0046295 glycolate biosynthetic process | IDA PMID:22523093 Human DJ-1 and its homologs are novel glyoxalases. | ACCEPT | Summary: DJ-1 produces glycolate from glyoxal via glyoxalase activity (PMID:22523093). IDA evidence. Reason: Core enzymatic product. Well-established. |
| GO:1902958 positive regulation of mitochondrial electron transport, NADH to ubiquinone | IMP PMID:19822128 DJ-1 binds to mitochondrial complex I and maintains its acti... | ACCEPT | Summary: DJ-1 binds complex I and maintains its NADH-to-ubiquinone electron transport activity (PMID:19822128). IMP evidence. Reason: Complex I activity maintenance is a well-characterized function supported by direct evidence. |
| GO:0003713 transcription coactivator activity | TAS PMID:16731528 DJ-1 transcriptionally up-regulates the human tyrosine hydro... | ACCEPT | Summary: DJ-1 acts as transcription coactivator by inhibiting PSF sumoylation (PMID:16731528). TAS evidence consistent with IGI evidence from PMID:15790595. Reason: Transcription coactivator activity is a core molecular function of DJ-1. |
| GO:0019899 enzyme binding | IPI PMID:19703902 Oxidative status of DJ-1-dependent activation of dopamine sy... | ACCEPT | Summary: DJ-1 binds TH and AADC enzymes to activate dopamine biosynthesis (PMID:19703902). Specific and informative. Reason: Enzyme binding to TH and AADC is a specific molecular function relevant to dopamine biosynthesis regulation. |
| GO:0034599 cellular response to oxidative stress | IDA PMID:19703902 Oxidative status of DJ-1-dependent activation of dopamine sy... | ACCEPT | Summary: DJ-1's dopamine biosynthesis regulation is oxidative status-dependent (PMID:19703902). Core oxidative stress response function. Reason: Oxidative stress response is the central function of DJ-1. IDA evidence. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | ACCEPT | Summary: DJ-1 identified in exosomes from expressed prostatic secretions in urine (PMID:23533145). Consistent with DJ-1 biomarker studies using urinary exosomes. Reason: Exosomal localization is supported by multiple HDA studies and is clinically relevant for DJ-1 as a PD biomarker. |
| GO:1903181 positive regulation of dopamine biosynthetic process | IDA PMID:19703902 Oxidative status of DJ-1-dependent activation of dopamine sy... | ACCEPT | Summary: DJ-1 directly activates TH and AADC to promote dopamine biosynthesis (PMID:19703902). IDA evidence. Reason: Dopamine biosynthesis regulation is a key function of DJ-1 directly relevant to Parkinson disease. |
| GO:0005515 protein binding | IPI PMID:24899725 Regulation of the VHL/HIF-1 pathway by DJ-1. | MARK AS OVER ANNOTATED | Summary: DJ-1 binds VHL in regulation of VHL/HIF-1 pathway (PMID:24899725). Generic protein binding. Reason: Generic protein binding is uninformative. The specific ubiquitin-protein transferase inhibitor activity (GO:0055105) from the same reference is more informative. |
| GO:0031397 negative regulation of protein ubiquitination | IDA PMID:24899725 Regulation of the VHL/HIF-1 pathway by DJ-1. | ACCEPT | Summary: DJ-1 inhibits VHL-mediated ubiquitination of HIF-1alpha (PMID:24899725). Consistent with DJ-1's general role in preventing target protein ubiquitination. Reason: Negative regulation of protein ubiquitination is a consistent function of DJ-1 across multiple targets (Nrf2, HIF-1alpha). |
| GO:0034599 cellular response to oxidative stress | IMP PMID:24899725 Regulation of the VHL/HIF-1 pathway by DJ-1. | ACCEPT | Summary: DJ-1 regulates VHL/HIF-1 pathway in response to oxidative stress (PMID:24899725). IMP evidence. Reason: Core oxidative stress response function confirmed in VHL/HIF-1 pathway context. |
| GO:0034599 cellular response to oxidative stress | IDA PMID:20969476 DJ-1 cleavage by matrix metalloproteinase 3 mediates oxidati... | ACCEPT | Summary: DJ-1 cleavage by MMP3 occurs during oxidative stress in dopaminergic cells (PMID:20969476). Core oxidative stress response. Reason: Core function. IDA evidence for cellular response to oxidative stress. |
| GO:0005739 mitochondrion | IDA PMID:23743200 DJ-1 cooperates with PYCR1 in cell protection against oxidat... | ACCEPT | Summary: Mitochondrial localization confirmed in PYCR1 cooperation study (PMID:23743200). Reason: Additional confirmation of mitochondrial localization. |
| GO:0019899 enzyme binding | IPI PMID:23743200 DJ-1 cooperates with PYCR1 in cell protection against oxidat... | ACCEPT | Summary: DJ-1 binds PYCR1 enzyme to cooperate in oxidative stress protection (PMID:23743200). Reason: Enzyme binding to PYCR1 is a specific and functionally relevant molecular function. |
| GO:0051881 regulation of mitochondrial membrane potential | IMP PMID:23743200 DJ-1 cooperates with PYCR1 in cell protection against oxidat... | KEEP AS NON CORE | Summary: DJ-1 cooperates with PYCR1 to maintain mitochondrial membrane potential during oxidative stress (PMID:23743200). Reason: Mitochondrial membrane potential regulation is a downstream consequence of DJ-1's mitochondrial protective function. |
| GO:0016684 oxidoreductase activity, acting on peroxide as acceptor | IDA PMID:24567322 DJ-1 is a copper chaperone acting on SOD1 activation. | ACCEPT | Summary: DJ-1 has peroxidase-like activity demonstrated in copper chaperone study (PMID:24567322). IDA evidence. Reason: Oxidoreductase activity on peroxide is supported by IDA evidence, consistent with IBA annotation. |
| GO:1903136 cuprous ion binding | IDA PMID:24144264 Structure of Cu(I)-bound DJ-1 reveals a biscysteinate metal ... | ACCEPT | Summary: DJ-1 binds Cu(I) at a biscysteinate binding site at the homodimer interface (PMID:24144264). Structural evidence. Reason: Cu(I) binding structurally characterized. Core metal-binding function essential for copper chaperone activity. Supporting Evidence: PMID:24144264 Structure of Cu(I)-bound DJ-1 reveals a biscysteinate metal binding site at the homodimer interface |
| GO:0005739 mitochondrion | IDA PMID:15944198 Mitochondrial localization of the Parkinson's disease relate... | ACCEPT | Summary: Mitochondrial localization of DJ-1 in human cells with implications for pathogenesis (PMID:15944198). Early study confirming mitochondrial localization. Reason: Well-established mitochondrial localization. |
| GO:0005829 cytosol | IDA PMID:15944198 Mitochondrial localization of the Parkinson's disease relate... | ACCEPT | Summary: Cytosolic localization confirmed in mitochondrial localization study (PMID:15944198). Reason: Well-established cytosolic localization. |
| GO:0097110 scaffold protein binding | IPI PMID:21785459 DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspas... | KEEP AS NON CORE | Summary: DJ-1 binds FADD scaffold protein to block TRAIL-induced apoptosis (PMID:21785459). Specific MF term. Reason: FADD scaffold binding is a specific interaction for TRAIL apoptosis inhibition, a non-core protective mechanism. |
| GO:0042743 hydrogen peroxide metabolic process | IDA PMID:24567322 DJ-1 is a copper chaperone acting on SOD1 activation. | ACCEPT | Summary: DJ-1 participates in H2O2 metabolism through its peroxidase-like activity (PMID:24567322). Related to copper chaperone function. Reason: H2O2 metabolism is consistent with DJ-1's oxidoreductase activity on peroxide. |
| GO:1903135 cupric ion binding | IDA PMID:24567322 DJ-1 is a copper chaperone acting on SOD1 activation. | ACCEPT | Summary: DJ-1 binds Cu(II) ions via Cys-106 binding site (PMID:24567322). Structural and biochemical evidence. Reason: Cu(II) binding is experimentally demonstrated and relevant to copper chaperone function. |
| GO:1903136 cuprous ion binding | IDA PMID:24567322 DJ-1 is a copper chaperone acting on SOD1 activation. | ACCEPT | Summary: DJ-1 binds Cu(I) ions, essential for copper transfer to SOD1 (PMID:24567322). IDA evidence. Reason: Cu(I) binding is core to DJ-1's copper chaperone activity for SOD1. |
| GO:0003690 double-stranded DNA binding | IDA NOT PMID:22683601 Nuclear translocation of DJ-1 during oxidative stress-induce... | ACCEPT | Summary: NOT annotation - DJ-1 does NOT bind double-stranded DNA directly (PMID:22683601). Consistent with its role as a transcriptional coactivator via protein-protein interactions rather than direct DNA binding. Reason: Important negated annotation clarifying DJ-1's mechanism of transcriptional regulation. |
| GO:0003697 single-stranded DNA binding | IDA NOT PMID:22683601 Nuclear translocation of DJ-1 during oxidative stress-induce... | ACCEPT | Summary: NOT annotation - DJ-1 does NOT bind single-stranded DNA (PMID:22683601). Consistent with other negated DNA binding annotations. Reason: Important negated annotation consistent with lack of direct DNA binding by DJ-1. |
| GO:0005515 protein binding | IPI PMID:22683601 Nuclear translocation of DJ-1 during oxidative stress-induce... | MARK AS OVER ANNOTATED | Summary: DJ-1 interactions in nuclear translocation study during oxidative stress (PMID:22683601). Generic protein binding. Reason: Generic protein binding is uninformative. |
| GO:0010629 negative regulation of gene expression | IDA PMID:22683601 Nuclear translocation of DJ-1 during oxidative stress-induce... | KEEP AS NON CORE | Summary: DJ-1 negatively regulates gene expression during nuclear translocation in oxidative stress (PMID:22683601). This may reflect DJ-1's dual role in transcriptional regulation. Reason: Negative regulation of gene expression is a context-dependent observation during oxidative stress. DJ-1 is primarily known as a positive transcriptional regulator. |
| GO:0016605 PML body | IDA PMID:22683601 Nuclear translocation of DJ-1 during oxidative stress-induce... | KEEP AS NON CORE | Summary: DJ-1 localizes to PML bodies during nuclear translocation under oxidative stress (PMID:22683601). Specific subnuclear localization. Reason: PML body localization is a specific observation during oxidative stress. Not a primary localization. |
| GO:0005829 cytosol | IDA PMID:22683601 Nuclear translocation of DJ-1 during oxidative stress-induce... | ACCEPT | Summary: Cytosolic localization confirmed in nuclear translocation study (PMID:22683601). Reason: Well-established cytosolic localization. |
| GO:0034599 cellular response to oxidative stress | IDA PMID:22683601 Nuclear translocation of DJ-1 during oxidative stress-induce... | ACCEPT | Summary: DJ-1 nuclear translocation during oxidative stress-induced neuronal cell death (PMID:22683601). Core function. Reason: Core oxidative stress response function confirmed by IDA. |
| GO:1903122 negative regulation of TRAIL-activated apoptotic signaling pathway | IMP PMID:21785459 DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspas... | KEEP AS NON CORE | Summary: DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspase-8 recruitment to FADD (PMID:21785459). Specific anti-apoptotic mechanism. Reason: TRAIL apoptosis inhibition is a specific non-core protective mechanism. |
| GO:1900182 positive regulation of protein localization to nucleus | IDA PMID:21097510 DJ-1 enhances cell survival through the binding of Cezanne, ... | KEEP AS NON CORE | Summary: DJ-1 promotes nuclear localization of NF-kappaB via Cezanne/OTUD7B binding (PMID:21097510). Reason: Downstream effect of DJ-1's NF-kappaB modulation. |
| GO:1903094 negative regulation of protein K48-linked deubiquitination | IDA PMID:21097510 DJ-1 enhances cell survival through the binding of Cezanne, ... | KEEP AS NON CORE | Summary: DJ-1 inhibits K48-linked deubiquitination by binding OTUD7B/Cezanne deubiquitinase (PMID:21097510). This modulates NF-kappaB signaling. Reason: K48-linked deubiquitination regulation is a specific mechanism within DJ-1's NF-kappaB modulation function. |
| GO:0019955 cytokine binding | IPI PMID:21097510 DJ-1 enhances cell survival through the binding of Cezanne, ... | KEEP AS NON CORE | Summary: DJ-1 binds CLCF1 cytokine in NF-kappaB signaling study (PMID:21097510). The functional significance of this cytokine interaction is unclear. Reason: Cytokine binding is a specific interaction observed in the NF-kappaB pathway context, but functional relevance is not well-characterized. |
| GO:0005634 nucleus | IDA PMID:15983381 Interaction of DJ-1 with Daxx inhibits apoptosis signal-regu... | ACCEPT | Summary: Nuclear localization confirmed in Daxx-ASK1 study (PMID:15983381). Reason: Well-established nuclear localization. |
| GO:0005737 cytoplasm | IDA PMID:15983381 Interaction of DJ-1 with Daxx inhibits apoptosis signal-regu... | ACCEPT | Summary: Cytoplasmic localization confirmed in Daxx-ASK1 study (PMID:15983381). Reason: Well-established cytoplasmic localization. |
| GO:0044388 small protein activating enzyme binding | IPI PMID:15983381 Interaction of DJ-1 with Daxx inhibits apoptosis signal-regu... | KEEP AS NON CORE | Summary: DJ-1 interacts with Daxx and sumoylation machinery in SUMO pathway context (PMID:15983381). Specific binding interaction in ubiquitin-like modification pathway. Reason: Interaction with SUMO pathway components is relevant to DJ-1's regulation of sumoylation but is a secondary function. |
| GO:0044390 ubiquitin-like protein conjugating enzyme binding | IPI PMID:15983381 Interaction of DJ-1 with Daxx inhibits apoptosis signal-regu... | KEEP AS NON CORE | Summary: DJ-1 interacts with ubiquitin-like protein conjugating enzymes in context of Daxx-ASK1 study (PMID:15983381). Reason: Interaction with SUMO conjugation machinery is secondary to DJ-1's core functions. |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | ACCEPT | Summary: DJ-1 detected in human sperm nucleus by proteomic characterization (PMID:21630459). HDA evidence. Reason: Nuclear localization confirmed in specialized tissue. Consistent with well-established nuclear localization. |
| GO:0005737 cytoplasm | IDA PMID:17510388 DJ-1 binds androgen receptor directly and mediates its activ... | ACCEPT | Summary: Cytoplasmic localization confirmed in androgen receptor study (PMID:17510388). Reason: Well-established cytoplasmic localization. |
| GO:0005739 mitochondrion | IMP PMID:21785459 DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspas... | ACCEPT | Summary: Mitochondrial localization confirmed in TRAIL apoptosis study (PMID:21785459). IMP evidence. Reason: Well-established mitochondrial localization. |
| GO:0005829 cytosol | IMP PMID:21785459 DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspas... | ACCEPT | Summary: Cytosolic localization confirmed in TRAIL apoptosis study (PMID:21785459). Reason: Well-established cytosolic localization. |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | ACCEPT | Summary: DJ-1 identified in human parotid gland exosomes by MudPIT proteomics (PMID:19199708). Consistent with biomarker applications. Reason: Exosomal localization confirmed by multiple independent HDA studies. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | ACCEPT | Summary: DJ-1 identified in urinary exosome proteomics (PMID:19056867). Consistent with DJ-1 as urinary biomarker. Reason: Urinary exosomal localization relevant to biomarker applications. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | ACCEPT | Summary: DJ-1 identified in B-cell exosome proteomics (PMID:20458337). Reason: Additional exosomal localization confirmation from B-cell study. |
| GO:0043523 regulation of neuron apoptotic process | IDA PMID:18711745 Mitochondrial localization of DJ-1 leads to enhanced neuropr... | KEEP AS NON CORE | Summary: DJ-1 regulates neuron apoptosis through mitochondrial localization-dependent neuroprotection (PMID:18711745). Reason: Neuron apoptosis regulation is a downstream neuroprotective phenotype. |
| GO:0043523 regulation of neuron apoptotic process | IDA PMID:20304780 Parkinson disease protein DJ-1 converts from a zymogen to a ... | KEEP AS NON CORE | Summary: DJ-1 regulates neuron apoptosis, with protease activity activated by C-terminal cleavage under oxidative stress (PMID:20304780). Reason: Neuron apoptosis regulation is a downstream neuroprotective phenotype. |
| GO:0043524 negative regulation of neuron apoptotic process | IDA PMID:22511790 Inactivation of Pink1 gene in vivo sensitizes dopamine-produ... | KEEP AS NON CORE | Summary: DJ-1 rescues PINK1-deficient neurons from MPTP-induced dopaminergic cell death (PMID:22511790). Genetic rescue experiment in mice. Reason: Anti-apoptotic neuroprotective phenotype. Downstream of core functions. |
| GO:2001237 negative regulation of extrinsic apoptotic signaling pathway | IMP PMID:21785459 DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspas... | KEEP AS NON CORE | Summary: DJ-1 inhibits extrinsic apoptotic signaling (TRAIL pathway) by blocking DISC assembly (PMID:21785459). Reason: Extrinsic apoptosis pathway regulation is a specific non-core protective mechanism. |
| GO:0003729 mRNA binding | IDA PMID:18626009 RNA binding activity of the recessive parkinsonism protein D... | ACCEPT | Summary: DJ-1 binds mRNAs with GG/CC motifs and partially inhibits their translation, dissociating under oxidative stress (PMID:18626009). RNA binding is a validated molecular function. Reason: mRNA binding is an experimentally validated molecular function of DJ-1, demonstrated with purified protein and in cells. It represents a distinct functional role. |
| GO:0005634 nucleus | IDA PMID:18711745 Mitochondrial localization of DJ-1 leads to enhanced neuropr... | ACCEPT | Summary: Nuclear localization confirmed with stress-dependent translocation from cytoplasm (PMID:18711745). Reason: Well-established nuclear localization. Supporting Evidence: PMID:18711745 Upon oxidant challenge, more DJ-1 translocates to mitochondria within 3 hr and subsequently to the nucleus by 12 hr |
| GO:0005737 cytoplasm | IDA PMID:18711745 Mitochondrial localization of DJ-1 leads to enhanced neuropr... | ACCEPT | Summary: Cytoplasm is the primary localization of DJ-1 under basal conditions (PMID:18711745). Reason: Well-established primary localization. Supporting Evidence: PMID:18711745 under basal conditions DJ-1 is present mostly in the cytoplasm and to a lesser extent in mitochondria and nucleus |
| GO:0005739 mitochondrion | IDA PMID:18711745 Mitochondrial localization of DJ-1 leads to enhanced neuropr... | ACCEPT | Summary: Mitochondrial localization confirmed with stress-dependent enhanced translocation (PMID:18711745). Mitochondrial DJ-1 provides strongest neuroprotection. Reason: Mitochondrial localization is functionally critical for DJ-1's neuroprotective activity. Supporting Evidence: PMID:18711745 mitochondrial targeting of DJ-1 provided a significantly stronger (55%) cytoprotection based on lactate dehydrogenase release |
| GO:0007005 mitochondrion organization | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation transferred from ortholog data. DJ-1 is required for correct mitochondrial morphology and function (UniProt). Consistent with PINK1-Parkin-DJ-1 complex role. Reason: Mitochondrion organization is supported by DJ-1's role in the PINK1-Parkin mitochondrial quality control pathway. |
| GO:0008233 peptidase activity | IDA PMID:20304780 Parkinson disease protein DJ-1 converts from a zymogen to a ... | UNDECIDED | Summary: Chen et al. reported DJ-1 converts from a zymogen to a protease by C-terminal cleavage under oxidative stress (PMID:20304780). However, earlier crystal structure studies found lack of proteolytic activity (PMID:12855764). The peptidase activity is weakly supported and controversial. Reason: Peptidase activity reported by one group but contradicted by structural studies. The crystal structure shows the Cys-106 position differs from related ThiJ proteases and is unlikely to support protease catalysis. |
| GO:0042803 protein homodimerization activity | IDA PMID:18711745 Mitochondrial localization of DJ-1 leads to enhanced neuropr... | ACCEPT | Summary: DJ-1 homodimerization confirmed by cross-linking experiments in mitochondrial and nuclear fractions (PMID:18711745). Functional dimer is the active form. Reason: Homodimerization is essential for DJ-1 function. Confirmed by multiple methods. Supporting Evidence: PMID:18711745 The predominant DJ-1 species in both mitochondria and nucleus is a dimer believed to be the functional form |
| GO:0050727 regulation of inflammatory response | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation from ortholog data. DJ-1 regulates inflammatory responses, particularly through NF-kappaB modulation (PMID:21097510) and microglial inflammatory pathways. Reason: Inflammatory response regulation is a secondary downstream effect, not a core molecular function. |
| GO:0005634 nucleus | IDA PMID:11477070 DJ-1 positively regulates the androgen receptor by impairing... | ACCEPT | Summary: Nuclear localization of DJ-1 confirmed in original androgen receptor signaling study (PMID:11477070). Reason: Well-established nuclear localization. |
| GO:0060765 regulation of androgen receptor signaling pathway | IDA PMID:11477070 DJ-1 positively regulates the androgen receptor by impairing... | KEEP AS NON CORE | Summary: DJ-1 positively regulates the androgen receptor by impairing PIASx-alpha binding to the receptor (PMID:11477070). Original study establishing DJ-1's role in AR signaling. Reason: Androgen receptor signaling regulation is a validated but non-core function of DJ-1, likely related to male fertility. |
| GO:0005634 nucleus | IDA PMID:12446870 Mutations in the DJ-1 gene associated with autosomal recessi... | ACCEPT | Summary: Nuclear localization confirmed in study identifying DJ-1 mutations associated with autosomal recessive early-onset Parkinsonism (PMID:12446870). Reason: Well-established nuclear localization. |
| GO:0005737 cytoplasm | IDA PMID:12446870 Mutations in the DJ-1 gene associated with autosomal recessi... | ACCEPT | Summary: Cytoplasmic localization confirmed in Parkinson disease mutation study (PMID:12446870). Reason: Well-established cytoplasmic localization. |
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