PRKN (Parkin, PARK2) is a 465-residue RING-between-RING (RBR) E3 ubiquitin ligase. Mutations in PRKN are the most common cause of autosomal recessive juvenile parkinsonism. Parkin has an N-terminal ubiquitin-like (Ubl) domain and four zinc-coordinating domains (RING0, RING1, IBR, RING2). It works as a RING/HECT hybrid: RING1 binds the E2~ubiquitin conjugate (UbcH7/UBE2L3), and ubiquitin is transferred via a thioester intermediate on the catalytic Cys431 in RING2. In resting cells Parkin is cytosolic and autoinhibited: the Ubl and RING0 domains occlude the E2-binding site and the catalytic cysteine. On damaged, depolarized mitochondria, PINK1 accumulates on the outer membrane and phosphorylates ubiquitin at Ser65. Phospho-ubiquitin recruits Parkin and promotes PINK1 phosphorylation of Ser65 in the Parkin Ubl, which fully releases autoinhibition. Activated Parkin ubiquitinates many outer-membrane proteins (mitofusins, Miro, VDAC1, TOM subunits), forming K6, K11, K48 and K63 chains. These chains are further phosphorylated by PINK1 in a feed-forward loop. The phospho-ubiquitin coat recruits autophagy receptors and drives mitophagy, while proteasomal degradation of mitofusins and Miro isolates and immobilizes the damaged organelle. USP30 and other deubiquitinases oppose Parkin action. Parkin also ubiquitinates many cytosolic and ER-associated substrates (e.g. Pael-R, PARIS/ZNF746, synphilin-1, Fbw7beta, RIPK3, NEMO), and these activities underlie reported roles in protection against unfolded-protein and oxidative stress, NF-kappaB signalling, necroptosis and synaptic function.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:23985028 S-Nitrosylation of parkin as a novel regulator of p53-mediat... | KEEP AS NON CORE | Summary: Parkin was reported to act as a transcriptional repressor of TP53. Reason: Experimental but contested non-canonical function; non-core. Supporting Evidence: PMID:23985028 Mutations in the gene encoding parkin, a neuroprotective protein with dual functions as an E3 ubiquitin ligase and transcriptional repressor of p53, are linked to familial forms of Parkinson's disease (PD). |
| GO:0000139 Golgi membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred Golgi membrane location. Reason: Minor location. |
| GO:0000151 ubiquitin ligase complex | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Parkin participates in reported multiprotein ligase complexes (with CHIP/Hsp70, FBXW7/Cul1, Fbxo7). Reason: Parkin mainly acts as a monomeric RBR E3; the complexes are context-specific. Supporting Evidence: PMID:12628165 Here we show that parkin functions in a multiprotein ubiquitin ligase complex that includes the F-box/WD repeat protein hSel-10 and Cullin-1. PMID:12150907 CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. |
| GO:0000151 ubiquitin ligase complex | IDA PMID:12150907 CHIP is associated with Parkin, a gene responsible for famil... | KEEP AS NON CORE | Summary: Parkin participates in reported multiprotein ligase complexes (with CHIP/Hsp70, FBXW7/Cul1, Fbxo7). Reason: Parkin mainly acts as a monomeric RBR E3; the complexes are context-specific. Supporting Evidence: PMID:12628165 Here we show that parkin functions in a multiprotein ubiquitin ligase complex that includes the F-box/WD repeat protein hSel-10 and Cullin-1. PMID:12150907 CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. |
| GO:0000151 ubiquitin ligase complex | IDA PMID:17314283 Parkin mediates neuroprotection through activation of Ikappa... | KEEP AS NON CORE | Summary: Parkin participates in reported multiprotein ligase complexes (with CHIP/Hsp70, FBXW7/Cul1, Fbxo7). Reason: Parkin mainly acts as a monomeric RBR E3; the complexes are context-specific. Supporting Evidence: PMID:12628165 Here we show that parkin functions in a multiprotein ubiquitin ligase complex that includes the F-box/WD repeat protein hSel-10 and Cullin-1. PMID:12150907 CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. |
| GO:0000151 ubiquitin ligase complex | IDA PMID:23933751 The Parkinson's disease-linked proteins Fbxo7 and Parkin int... | KEEP AS NON CORE | Summary: Parkin participates in reported multiprotein ligase complexes (with CHIP/Hsp70, FBXW7/Cul1, Fbxo7). Reason: Parkin mainly acts as a monomeric RBR E3; the complexes are context-specific. Supporting Evidence: PMID:12628165 Here we show that parkin functions in a multiprotein ubiquitin ligase complex that includes the F-box/WD repeat protein hSel-10 and Cullin-1. PMID:12150907 CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. |
| GO:0000209 protein polyubiquitination | IDA PMID:12150907 CHIP is associated with Parkin, a gene responsible for famil... | ACCEPT | Summary: Parkin catalyses polyubiquitination of substrates. Reason: Directly shown. Supporting Evidence: PMID:32047033 Here, we demonstrate that VDAC1 can be either mono- or polyubiquitinated by Parkin in a PINK1-dependent manner. PMID:12150907 CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. |
| GO:0000209 protein polyubiquitination | IDA PMID:16227987 Dopamine covalently modifies and functionally inactivates pa... | ACCEPT | Summary: Parkin catalyses polyubiquitination of substrates. Reason: Directly shown. Supporting Evidence: PMID:32047033 Here, we demonstrate that VDAC1 can be either mono- or polyubiquitinated by Parkin in a PINK1-dependent manner. PMID:12150907 CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. |
| GO:0000209 protein polyubiquitination | IDA PMID:18541373 Parkin is ubiquitinated by Nrdp1 and abrogates Nrdp1-induced... | ACCEPT | Summary: Parkin catalyses polyubiquitination of substrates. Reason: Directly shown. Supporting Evidence: PMID:32047033 Here, we demonstrate that VDAC1 can be either mono- or polyubiquitinated by Parkin in a PINK1-dependent manner. PMID:12150907 CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. |
| GO:0000209 protein polyubiquitination | IDA PMID:19880420 Phosphorylation of parkin by Parkinson disease-linked kinase... | ACCEPT | Summary: Parkin catalyses polyubiquitination of substrates. Reason: Directly shown. Supporting Evidence: PMID:32047033 Here, we demonstrate that VDAC1 can be either mono- or polyubiquitinated by Parkin in a PINK1-dependent manner. PMID:12150907 CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. |
| GO:0000209 protein polyubiquitination | IMP PMID:32047033 Decision between mitophagy and apoptosis by Parkin via VDAC1... | ACCEPT | Summary: Parkin catalyses polyubiquitination of substrates. Reason: Directly shown. Supporting Evidence: PMID:32047033 Here, we demonstrate that VDAC1 can be either mono- or polyubiquitinated by Parkin in a PINK1-dependent manner. PMID:12150907 CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. |
| GO:0000266 mitochondrial fission | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Parkin promotes mitochondrial fragmentation by ubiquitinating and degrading mitofusins (ortholog transfer). Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:20871098 The ubiquitination of several mitochondrial proteins, including mitofusin 1 and mitofusin 2, were detected within 3 h of CCCP treatment. |
| GO:0000422 autophagy of mitochondrion | IDA PMID:25621951 USP30 and parkin homeostatically regulate atypical ubiquitin... | ACCEPT | Summary: Parkin is recruited to depolarized mitochondria and mediates their autophagic elimination. Reason: Core process. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. PMID:19029340 After recruitment, Parkin mediates the engulfment of mitochondria by autophagosomes and the selective elimination of impaired mitochondria. |
| GO:0000422 autophagy of mitochondrion | IMP PMID:19029340 Parkin is recruited selectively to impaired mitochondria and... | ACCEPT | Summary: Parkin is recruited to depolarized mitochondria and mediates their autophagic elimination. Reason: Core process. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. PMID:19029340 After recruitment, Parkin mediates the engulfment of mitochondria by autophagosomes and the selective elimination of impaired mitochondria. |
| GO:0000422 autophagy of mitochondrion | IMP PMID:23933751 The Parkinson's disease-linked proteins Fbxo7 and Parkin int... | ACCEPT | Summary: Parkin is recruited to depolarized mitochondria and mediates their autophagic elimination. Reason: Core process. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. PMID:19029340 After recruitment, Parkin mediates the engulfment of mitochondria by autophagosomes and the selective elimination of impaired mitochondria. |
| GO:0000422 autophagy of mitochondrion | IMP PMID:24896179 The mitochondrial deubiquitinase USP30 opposes parkin-mediat... | ACCEPT | Summary: Parkin is recruited to depolarized mitochondria and mediates their autophagic elimination. Reason: Core process. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. PMID:19029340 After recruitment, Parkin mediates the engulfment of mitochondria by autophagosomes and the selective elimination of impaired mitochondria. |
| GO:0000423 mitophagy | IBA GO_REF:0000033 | ACCEPT | Summary: Parkin mediates ubiquitin-dependent mitophagy downstream of PINK1. Reason: Core process, supported by multiple experimental studies and the IBA. Supporting Evidence: PMID:19029340 After recruitment, Parkin mediates the engulfment of mitochondria by autophagosomes and the selective elimination of impaired mitochondria. PMID:23685073 we show that RAD6A acts as an E2 ubiquitin-conjugating enzyme that, in combination with an E3 ubiquitin ligase such as Parkin, ubiquitinates mitochondrial proteins to facilitate the clearance of dysfunctional mitochondria in cells. PMID:28017329 PHB2 is required for Parkin-induced mitophagy in mammalian cells and for the clearance of paternal mitochondria after embryonic fertilization in C. elegans. |
| GO:0000423 mitophagy | IDA PMID:23685073 Mutations in the intellectual disability gene Ube2a cause ne... | ACCEPT | Summary: Parkin mediates ubiquitin-dependent mitophagy downstream of PINK1. Reason: Core process, supported by multiple experimental studies and the IBA. Supporting Evidence: PMID:19029340 After recruitment, Parkin mediates the engulfment of mitochondria by autophagosomes and the selective elimination of impaired mitochondria. PMID:23685073 we show that RAD6A acts as an E2 ubiquitin-conjugating enzyme that, in combination with an E3 ubiquitin ligase such as Parkin, ubiquitinates mitochondrial proteins to facilitate the clearance of dysfunctional mitochondria in cells. PMID:28017329 PHB2 is required for Parkin-induced mitophagy in mammalian cells and for the clearance of paternal mitochondria after embryonic fertilization in C. elegans. |
| GO:0000423 mitophagy | IDA PMID:28017329 Prohibitin 2 Is an Inner Mitochondrial Membrane Mitophagy Re... | ACCEPT | Summary: Parkin mediates ubiquitin-dependent mitophagy downstream of PINK1. Reason: Core process, supported by multiple experimental studies and the IBA. Supporting Evidence: PMID:19029340 After recruitment, Parkin mediates the engulfment of mitochondria by autophagosomes and the selective elimination of impaired mitochondria. PMID:23685073 we show that RAD6A acts as an E2 ubiquitin-conjugating enzyme that, in combination with an E3 ubiquitin ligase such as Parkin, ubiquitinates mitochondrial proteins to facilitate the clearance of dysfunctional mitochondria in cells. PMID:28017329 PHB2 is required for Parkin-induced mitophagy in mammalian cells and for the clearance of paternal mitochondria after embryonic fertilization in C. elegans. |
| GO:0000423 mitophagy | IEA GO_REF:0000120 | ACCEPT | Summary: Parkin mediates ubiquitin-dependent mitophagy downstream of PINK1. Reason: Core process, supported by multiple experimental studies and the IBA. Supporting Evidence: PMID:19029340 After recruitment, Parkin mediates the engulfment of mitochondria by autophagosomes and the selective elimination of impaired mitochondria. PMID:23685073 we show that RAD6A acts as an E2 ubiquitin-conjugating enzyme that, in combination with an E3 ubiquitin ligase such as Parkin, ubiquitinates mitochondrial proteins to facilitate the clearance of dysfunctional mitochondria in cells. PMID:28017329 PHB2 is required for Parkin-induced mitophagy in mammalian cells and for the clearance of paternal mitochondria after embryonic fertilization in C. elegans. |
| GO:0001664 G protein-coupled receptor binding | IPI PMID:12150907 CHIP is associated with Parkin, a gene responsible for famil... | KEEP AS NON CORE | Summary: Parkin binds its substrate Pael-R (GPR37), a GPCR, in a complex with CHIP and Hsp70. Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:12150907 CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. |
| GO:0003714 transcription corepressor activity | IDA PMID:23985028 S-Nitrosylation of parkin as a novel regulator of p53-mediat... | KEEP AS NON CORE | Summary: Parkin was reported to act as a transcriptional repressor of TP53, an activity inhibited by S-nitrosylation. Reason: A non-canonical and still debated activity of an E3 ligase; non-core. Supporting Evidence: PMID:23985028 Mutations in the gene encoding parkin, a neuroprotective protein with dual functions as an E3 ubiquitin ligase and transcriptional repressor of p53, are linked to familial forms of Parkinson's disease (PD). |
| GO:0003779 actin binding | IPI PMID:21753002 Parkin interacts with Ambra1 to induce mitophagy. | MARK AS OVER ANNOTATED | Summary: Actin detected as an interactor in a co-immunoprecipitation study focused on Ambra1. Reason: Probably an incidental co-purification; no evidence for a specific actin-binding function of Parkin. Supporting Evidence: PMID:21753002 These data identify interaction of Parkin with Ambra1 as a key mechanism for induction of the final clearance step of Parkin-mediated mitophagy. |
| GO:0004842 ubiquitin-protein transferase activity | EXP PMID:31358971 The AMPK-Parkin axis negatively regulates necroptosis and tu... | ACCEPT | Summary: Parkin transfers ubiquitin to substrates (E3 activity). Reason: Correct; GO:0061630 is more specific. Supporting Evidence: PMID:11078524 These results suggest that Parkin functions as an E3 ubiquitin-protein ligase through its ring domains and that it may control protein levels via ubiquitination. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:11078524 Parkin functions as an E2-dependent ubiquitin- protein ligas... | ACCEPT | Summary: Parkin transfers ubiquitin to substrates (E3 activity). Reason: Correct; GO:0061630 is more specific. Supporting Evidence: PMID:11078524 These results suggest that Parkin functions as an E3 ubiquitin-protein ligase through its ring domains and that it may control protein levels via ubiquitination. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:15728840 Parkin mediates nonclassical, proteasomal-independent ubiqui... | ACCEPT | Summary: Parkin transfers ubiquitin to substrates (E3 activity). Reason: Correct; GO:0061630 is more specific. Supporting Evidence: PMID:11078524 These results suggest that Parkin functions as an E3 ubiquitin-protein ligase through its ring domains and that it may control protein levels via ubiquitination. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:17097639 Parkin is an E3 ubiquitin-ligase for normal and mutant ataxi... | ACCEPT | Summary: Parkin transfers ubiquitin to substrates (E3 activity). Reason: Correct; GO:0061630 is more specific. Supporting Evidence: PMID:11078524 These results suggest that Parkin functions as an E3 ubiquitin-protein ligase through its ring domains and that it may control protein levels via ubiquitination. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:18541373 Parkin is ubiquitinated by Nrdp1 and abrogates Nrdp1-induced... | ACCEPT | Summary: Parkin transfers ubiquitin to substrates (E3 activity). Reason: Correct; GO:0061630 is more specific. Supporting Evidence: PMID:11078524 These results suggest that Parkin functions as an E3 ubiquitin-protein ligase through its ring domains and that it may control protein levels via ubiquitination. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:20889974 Parkin mono-ubiquitinates Bcl-2 and regulates autophagy. | ACCEPT | Summary: Parkin transfers ubiquitin to substrates (E3 activity). Reason: Correct; GO:0061630 is more specific. Supporting Evidence: PMID:11078524 These results suggest that Parkin functions as an E3 ubiquitin-protein ligase through its ring domains and that it may control protein levels via ubiquitination. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:21376232 PARIS (ZNF746) repression of PGC-1Ξ± contributes to neurodege... | ACCEPT | Summary: Parkin transfers ubiquitin to substrates (E3 activity). Reason: Correct; GO:0061630 is more specific. Supporting Evidence: PMID:11078524 These results suggest that Parkin functions as an E3 ubiquitin-protein ligase through its ring domains and that it may control protein levels via ubiquitination. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:24784582 Ubiquitin is phosphorylated by PINK1 to activate parkin. | ACCEPT | Summary: Parkin transfers ubiquitin to substrates (E3 activity). Reason: Correct; GO:0061630 is more specific. Supporting Evidence: PMID:11078524 These results suggest that Parkin functions as an E3 ubiquitin-protein ligase through its ring domains and that it may control protein levels via ubiquitination. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:24896179 The mitochondrial deubiquitinase USP30 opposes parkin-mediat... | ACCEPT | Summary: Parkin transfers ubiquitin to substrates (E3 activity). Reason: Correct; GO:0061630 is more specific. Supporting Evidence: PMID:11078524 These results suggest that Parkin functions as an E3 ubiquitin-protein ligase through its ring domains and that it may control protein levels via ubiquitination. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. |
| GO:0004842 ubiquitin-protein transferase activity | IEA GO_REF:0000002 | ACCEPT | Summary: Parkin transfers ubiquitin to substrates (E3 activity). Reason: Correct; GO:0061630 is more specific. Supporting Evidence: PMID:11078524 These results suggest that Parkin functions as an E3 ubiquitin-protein ligase through its ring domains and that it may control protein levels via ubiquitination. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. |
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-HSA-5667111 | ACCEPT | Summary: Parkin transfers ubiquitin to substrates (E3 activity). Reason: Correct; GO:0061630 is more specific. Supporting Evidence: PMID:11078524 These results suggest that Parkin functions as an E3 ubiquitin-protein ligase through its ring domains and that it may control protein levels via ubiquitination. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. |
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-HSA-9834070 | ACCEPT | Summary: Parkin transfers ubiquitin to substrates (E3 activity). Reason: Correct; GO:0061630 is more specific. Supporting Evidence: PMID:11078524 These results suggest that Parkin functions as an E3 ubiquitin-protein ligase through its ring domains and that it may control protein levels via ubiquitination. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. |
| GO:0005515 protein binding | IPI PMID:10888878 Familial Parkinson disease gene product, parkin, is a ubiqui... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:11078524 Parkin functions as an E2-dependent ubiquitin- protein ligas... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:11439185 An unfolded putative transmembrane polypeptide, which can le... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:11590439 Parkin ubiquitinates the alpha-synuclein-interacting protein... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:12364339 Parkin accumulation in aggresomes due to proteasome impairme... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:12628165 Parkin is a component of an SCF-like ubiquitin ligase comple... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:12925569 The autosomal recessive juvenile Parkinson disease gene prod... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:14532270 A product of the human gene adjacent to parkin is a componen... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:15603737 BAG5 inhibits parkin and enhances dopaminergic neuron degene... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:15728840 Parkin mediates nonclassical, proteasomal-independent ubiqui... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:16096643 14-3-3eta is a novel regulator of parkin ubiquitin ligase. | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:16332688 Parkin ubiquitinates and promotes the degradation of RanBP2. | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:16352719 Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, ... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:17097639 Parkin is an E3 ubiquitin-ligase for normal and mutant ataxi... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:19036992 Direct binding with histone deacetylase 6 mediates the rever... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:19060904 An empirical framework for binary interactome mapping. | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:19146857 Programmed cell death-2 isoform1 is ubiquitinated by parkin ... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:19229105 Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex p... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:19725078 Proteomic analysis of increased Parkin expression and its in... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:19725078 Proteomic analysis of increased Parkin expression and its in... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:19725078 Proteomic analysis of increased Parkin expression and its in... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:19725078 Proteomic analysis of increased Parkin expression and its in... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:19725078 Proteomic analysis of increased Parkin expression and its in... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:19725078 Proteomic analysis of increased Parkin expression and its in... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:19725078 Proteomic analysis of increased Parkin expression and its in... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:19725078 Proteomic analysis of increased Parkin expression and its in... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:19725078 Proteomic analysis of increased Parkin expression and its in... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:19725078 Proteomic analysis of increased Parkin expression and its in... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:19966284 PINK1-dependent recruitment of Parkin to mitochondria in mit... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:20153330 PINK1 is recruited to mitochondria with parkin and associate... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:20889486 Molecular chaperone-mediated rescue of mitophagy by a Parkin... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:20889974 Parkin mono-ubiquitinates Bcl-2 and regulates autophagy. | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:21376232 PARIS (ZNF746) repression of PGC-1Ξ± contributes to neurodege... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:21753002 Parkin interacts with Ambra1 to induce mitophagy. | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:22078885 PINK1 and Parkin target Miro for phosphorylation and degrada... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:22082830 Parkin interacts with Klokin1 for mitochondrial import and m... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:22939624 Quantitative analysis of HSP90-client interactions reveals p... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:23453807 The E3 ligase parkin maintains mitochondrial integrity by in... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:23620051 PINK1-phosphorylated mitofusin 2 is a Parkin receptor for cu... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:23858059 Parkin-dependent degradation of the F-box protein Fbw7Ξ² prom... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:23933751 The Parkinson's disease-linked proteins Fbxo7 and Parkin int... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:23933751 The Parkinson's disease-linked proteins Fbxo7 and Parkin int... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:23933751 The Parkinson's disease-linked proteins Fbxo7 and Parkin int... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:24063750 Ataxin-3 is a multivalent ligand for the parkin Ubl domain. | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:24270810 High-content genome-wide RNAi screens identify regulators of... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:24270810 High-content genome-wide RNAi screens identify regulators of... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:24270810 High-content genome-wide RNAi screens identify regulators of... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:24357652 Cytosolic cleaved PINK1 represses Parkin translocation to mi... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:24660806 Parkin is activated by PINK1-dependent phosphorylation of ub... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:24722188 Protein interaction network of alternatively spliced isoform... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:25244949 Hepatitis C virus core protein suppresses mitophagy by inter... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:25959826 Quantitative interaction proteomics of neurodegenerative dis... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:30455355 Physiological and pathophysiological characteristics of atax... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Protein-protein interaction (e.g. with substrates, E2s, PINK1, chaperones, or high-throughput interactome partners). Reason: Generic protein binding is uninformative. The informative Parkin activities are captured by ubiquitin protein ligase activity, ubiquitin-conjugating enzyme binding and ubiquitin binding. Removal does not imply the interactions are false. |
| GO:0005634 nucleus | EXP PMID:16955485 Functional modulation of parkin through physical interaction... | KEEP AS NON CORE | Summary: A nuclear pool of Parkin has been reported (SUMO-1 association promotes nuclear transport; p53 promoter binding). Reason: Minor location; non-core. Supporting Evidence: PMID:16955485 Moreover, the physical association of SUMO-1 with parkin results in an increase in the nuclear transport of parkin as well as its self-ubiquitination. |
| GO:0005634 nucleus | IDA PMID:23985028 S-Nitrosylation of parkin as a novel regulator of p53-mediat... | KEEP AS NON CORE | Summary: A nuclear pool of Parkin has been reported (SUMO-1 association promotes nuclear transport; p53 promoter binding). Reason: Minor location; non-core. Supporting Evidence: PMID:16955485 Moreover, the physical association of SUMO-1 with parkin results in an increase in the nuclear transport of parkin as well as its self-ubiquitination. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: A nuclear pool of Parkin has been reported (SUMO-1 association promotes nuclear transport; p53 promoter binding). Reason: Minor location; non-core. Supporting Evidence: PMID:16955485 Moreover, the physical association of SUMO-1 with parkin results in an increase in the nuclear transport of parkin as well as its self-ubiquitination. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Parkin is a predominantly cytosolic protein that translocates to damaged mitochondria. Reason: Correct location of the resting pool. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005737 cytoplasm | IDA PMID:17512523 Parkin interacts with LIM Kinase 1 and reduces its cofilin-p... | ACCEPT | Summary: Parkin is a predominantly cytosolic protein that translocates to damaged mitochondria. Reason: Correct location of the resting pool. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005737 cytoplasm | IDA PMID:19591802 Parkin protects dopaminergic neurons from excessive Wnt/beta... | ACCEPT | Summary: Parkin is a predominantly cytosolic protein that translocates to damaged mitochondria. Reason: Correct location of the resting pool. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005737 cytoplasm | IDA PMID:21376232 PARIS (ZNF746) repression of PGC-1Ξ± contributes to neurodege... | ACCEPT | Summary: Parkin is a predominantly cytosolic protein that translocates to damaged mitochondria. Reason: Correct location of the resting pool. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005737 cytoplasm | IDA PMID:23858059 Parkin-dependent degradation of the F-box protein Fbw7Ξ² prom... | ACCEPT | Summary: Parkin is a predominantly cytosolic protein that translocates to damaged mitochondria. Reason: Correct location of the resting pool. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005737 cytoplasm | IDA PMID:23985028 S-Nitrosylation of parkin as a novel regulator of p53-mediat... | ACCEPT | Summary: Parkin is a predominantly cytosolic protein that translocates to damaged mitochondria. Reason: Correct location of the resting pool. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005737 cytoplasm | IDA PMID:25244949 Hepatitis C virus core protein suppresses mitophagy by inter... | ACCEPT | Summary: Parkin is a predominantly cytosolic protein that translocates to damaged mitochondria. Reason: Correct location of the resting pool. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Parkin is a predominantly cytosolic protein that translocates to damaged mitochondria. Reason: Correct location of the resting pool. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005739 mitochondrion | EXP PMID:22082830 Parkin interacts with Klokin1 for mitochondrial import and m... | ACCEPT | Summary: Parkin translocates to (damaged) mitochondria. Reason: Correct; GO:0005741 is more specific. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. PMID:22082830 Parkin was preferentially localized in the mitochondria of cultured cells. |
| GO:0005739 mitochondrion | EXP PMID:23620051 PINK1-phosphorylated mitofusin 2 is a Parkin receptor for cu... | ACCEPT | Summary: Parkin translocates to (damaged) mitochondria. Reason: Correct; GO:0005741 is more specific. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. PMID:22082830 Parkin was preferentially localized in the mitochondria of cultured cells. |
| GO:0005739 mitochondrion | EXP PMID:23754282 Parkin-catalyzed ubiquitin-ester transfer is triggered by PI... | ACCEPT | Summary: Parkin translocates to (damaged) mitochondria. Reason: Correct; GO:0005741 is more specific. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. PMID:22082830 Parkin was preferentially localized in the mitochondria of cultured cells. |
| GO:0005739 mitochondrion | EXP PMID:24898855 MUL1 acts in parallel to the PINK1/parkin pathway in regulat... | ACCEPT | Summary: Parkin translocates to (damaged) mitochondria. Reason: Correct; GO:0005741 is more specific. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. PMID:22082830 Parkin was preferentially localized in the mitochondria of cultured cells. |
| GO:0005739 mitochondrion | IDA PMID:18957282 PINK1 controls mitochondrial localization of Parkin through ... | ACCEPT | Summary: Parkin translocates to (damaged) mitochondria. Reason: Correct; GO:0005741 is more specific. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. PMID:22082830 Parkin was preferentially localized in the mitochondria of cultured cells. |
| GO:0005739 mitochondrion | IDA PMID:19229105 Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex p... | ACCEPT | Summary: Parkin translocates to (damaged) mitochondria. Reason: Correct; GO:0005741 is more specific. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. PMID:22082830 Parkin was preferentially localized in the mitochondria of cultured cells. |
| GO:0005739 mitochondrion | IDA PMID:20889974 Parkin mono-ubiquitinates Bcl-2 and regulates autophagy. | ACCEPT | Summary: Parkin translocates to (damaged) mitochondria. Reason: Correct; GO:0005741 is more specific. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. PMID:22082830 Parkin was preferentially localized in the mitochondria of cultured cells. |
| GO:0005739 mitochondrion | IDA PMID:23933751 The Parkinson's disease-linked proteins Fbxo7 and Parkin int... | ACCEPT | Summary: Parkin translocates to (damaged) mitochondria. Reason: Correct; GO:0005741 is more specific. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. PMID:22082830 Parkin was preferentially localized in the mitochondria of cultured cells. |
| GO:0005739 mitochondrion | IDA PMID:25244949 Hepatitis C virus core protein suppresses mitophagy by inter... | ACCEPT | Summary: Parkin translocates to (damaged) mitochondria. Reason: Correct; GO:0005741 is more specific. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. PMID:22082830 Parkin was preferentially localized in the mitochondria of cultured cells. |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: Parkin translocates to (damaged) mitochondria. Reason: Correct; GO:0005741 is more specific. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. PMID:22082830 Parkin was preferentially localized in the mitochondria of cultured cells. |
| GO:0005739 mitochondrion | IMP PMID:19029340 Parkin is recruited selectively to impaired mitochondria and... | ACCEPT | Summary: Parkin translocates to (damaged) mitochondria. Reason: Correct; GO:0005741 is more specific. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. PMID:22082830 Parkin was preferentially localized in the mitochondria of cultured cells. |
| GO:0005739 mitochondrion | IMP PMID:21508222 Mitochondrial Parkin recruitment is impaired in neurons deri... | ACCEPT | Summary: Parkin translocates to (damaged) mitochondria. Reason: Correct; GO:0005741 is more specific. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. PMID:22082830 Parkin was preferentially localized in the mitochondria of cultured cells. |
| GO:0005741 mitochondrial outer membrane | IDA PMID:18957282 PINK1 controls mitochondrial localization of Parkin through ... | ACCEPT | Summary: Parkin is recruited to the outer membrane of depolarized mitochondria, where it ubiquitinates outer-membrane proteins. Reason: Core functional location. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. PMID:23620051 Parkin bound to Mfn2 in a PINK1-dependent manner; PINK1 phosphorylated Mfn2 and promoted its Parkin-mediated ubiqitination. |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Parkin is recruited to the outer membrane of depolarized mitochondria, where it ubiquitinates outer-membrane proteins. Reason: Core functional location. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. PMID:23620051 Parkin bound to Mfn2 in a PINK1-dependent manner; PINK1 phosphorylated Mfn2 and promoted its Parkin-mediated ubiqitination. |
| GO:0005741 mitochondrial outer membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Parkin is recruited to the outer membrane of depolarized mitochondria, where it ubiquitinates outer-membrane proteins. Reason: Core functional location. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. PMID:23620051 Parkin bound to Mfn2 in a PINK1-dependent manner; PINK1 phosphorylated Mfn2 and promoted its Parkin-mediated ubiqitination. |
| GO:0005783 endoplasmic reticulum | EXP PMID:19501131 Evidence for the presence of full-length PARK2 mRNA and Park... | KEEP AS NON CORE | Summary: A fraction of Parkin associates with the ER, where it ubiquitinates misfolded ER-derived substrates such as Pael-R. Reason: Minor location relative to cytosol and mitochondria. Supporting Evidence: PMID:11439185 Parkin specifically ubiquitinates this receptor in the presence of ubiquitin-conjugating enzymes resident in the endoplasmic reticulum and promotes the degradation of insoluble Pael receptor, resulting in suppression of the cell death induced by Pael receptor overexpression. |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: A fraction of Parkin associates with the ER, where it ubiquitinates misfolded ER-derived substrates such as Pael-R. Reason: Minor location relative to cytosol and mitochondria. Supporting Evidence: PMID:11439185 Parkin specifically ubiquitinates this receptor in the presence of ubiquitin-conjugating enzymes resident in the endoplasmic reticulum and promotes the degradation of insoluble Pael receptor, resulting in suppression of the cell death induced by Pael receptor overexpression. |
| GO:0005783 endoplasmic reticulum | IDA PMID:12150907 CHIP is associated with Parkin, a gene responsible for famil... | KEEP AS NON CORE | Summary: A fraction of Parkin associates with the ER, where it ubiquitinates misfolded ER-derived substrates such as Pael-R. Reason: Minor location relative to cytosol and mitochondria. Supporting Evidence: PMID:11439185 Parkin specifically ubiquitinates this receptor in the presence of ubiquitin-conjugating enzymes resident in the endoplasmic reticulum and promotes the degradation of insoluble Pael receptor, resulting in suppression of the cell death induced by Pael receptor overexpression. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: A fraction of Parkin associates with the ER, where it ubiquitinates misfolded ER-derived substrates such as Pael-R. Reason: Minor location relative to cytosol and mitochondria. Supporting Evidence: PMID:11439185 Parkin specifically ubiquitinates this receptor in the presence of ubiquitin-conjugating enzymes resident in the endoplasmic reticulum and promotes the degradation of insoluble Pael receptor, resulting in suppression of the cell death induced by Pael receptor overexpression. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred ER membrane location. Reason: Minor location. |
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Parkin has been detected at the Golgi in some cell types. Reason: Minor location; not where Parkin performs its core function. Supporting Evidence: PMID:17097639 Parkin reduced abnormalities in Golgi morphology induced by mutant ataxin-2 and decreased ataxin-2 induced cytotoxicity. |
| GO:0005794 Golgi apparatus | IDA PMID:17097639 Parkin is an E3 ubiquitin-ligase for normal and mutant ataxi... | KEEP AS NON CORE | Summary: Parkin has been detected at the Golgi in some cell types. Reason: Minor location; not where Parkin performs its core function. Supporting Evidence: PMID:17097639 Parkin reduced abnormalities in Golgi morphology induced by mutant ataxin-2 and decreased ataxin-2 induced cytotoxicity. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | IDA PMID:19029340 Parkin is recruited selectively to impaired mitochondria and... | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | IDA PMID:19229105 Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex p... | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | IDA PMID:19880420 Phosphorylation of parkin by Parkinson disease-linked kinase... | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | IDA PMID:20889974 Parkin mono-ubiquitinates Bcl-2 and regulates autophagy. | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | IDA PMID:21753002 Parkin interacts with Ambra1 to induce mitophagy. | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | IDA PMID:23933751 The Parkinson's disease-linked proteins Fbxo7 and Parkin int... | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | IDA PMID:24751536 PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquit... | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | IEA GO_REF:0000120 | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | IMP PMID:21508222 Mitochondrial Parkin recruitment is impaired in neurons deri... | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5658574 | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5667111 | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5688837 | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5689085 | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5689111 | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9641089 | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9641096 | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9641109 | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9641111 | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9641127 | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9793472 | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9793485 | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9834070 | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835009 | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835011 | ACCEPT | Summary: Parkin resides in the cytosol in an autoinhibited state and is recruited from there to depolarized mitochondria. Reason: Correct. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0006511 ubiquitin-dependent protein catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Parkin ubiquitinates substrates for degradation (e.g. synaptotagmin XI, ataxin-2). Reason: Direct consequence of its E3 activity. Supporting Evidence: PMID:12925569 Parkin-mediated ubiquitination also enhances the turnover of sytXI. PMID:10888878 ubiquitin-protein ligase collaborating with the ubiquitin-conjugating enzyme UbcH7 |
| GO:0006511 ubiquitin-dependent protein catabolic process | IDA PMID:12925569 The autosomal recessive juvenile Parkinson disease gene prod... | ACCEPT | Summary: Parkin ubiquitinates substrates for degradation (e.g. synaptotagmin XI, ataxin-2). Reason: Direct consequence of its E3 activity. Supporting Evidence: PMID:12925569 Parkin-mediated ubiquitination also enhances the turnover of sytXI. PMID:10888878 ubiquitin-protein ligase collaborating with the ubiquitin-conjugating enzyme UbcH7 |
| GO:0006511 ubiquitin-dependent protein catabolic process | IDA PMID:17097639 Parkin is an E3 ubiquitin-ligase for normal and mutant ataxi... | ACCEPT | Summary: Parkin ubiquitinates substrates for degradation (e.g. synaptotagmin XI, ataxin-2). Reason: Direct consequence of its E3 activity. Supporting Evidence: PMID:12925569 Parkin-mediated ubiquitination also enhances the turnover of sytXI. PMID:10888878 ubiquitin-protein ligase collaborating with the ubiquitin-conjugating enzyme UbcH7 |
| GO:0006511 ubiquitin-dependent protein catabolic process | NAS PMID:12628165 Parkin is a component of an SCF-like ubiquitin ligase comple... | ACCEPT | Summary: Parkin ubiquitinates substrates for degradation (e.g. synaptotagmin XI, ataxin-2). Reason: Direct consequence of its E3 activity. Supporting Evidence: PMID:12925569 Parkin-mediated ubiquitination also enhances the turnover of sytXI. PMID:10888878 ubiquitin-protein ligase collaborating with the ubiquitin-conjugating enzyme UbcH7 |
| GO:0006511 ubiquitin-dependent protein catabolic process | TAS PMID:10888878 Familial Parkinson disease gene product, parkin, is a ubiqui... | ACCEPT | Summary: Parkin ubiquitinates substrates for degradation (e.g. synaptotagmin XI, ataxin-2). Reason: Direct consequence of its E3 activity. Supporting Evidence: PMID:12925569 Parkin-mediated ubiquitination also enhances the turnover of sytXI. PMID:10888878 ubiquitin-protein ligase collaborating with the ubiquitin-conjugating enzyme UbcH7 |
| GO:0006513 protein monoubiquitination | IDA PMID:20889974 Parkin mono-ubiquitinates Bcl-2 and regulates autophagy. | ACCEPT | Summary: Parkin monoubiquitinates substrates (e.g. Bcl-2, VDAC1). Reason: Directly shown. Supporting Evidence: PMID:20889974 Parkin directly binds to Bcl-2 via its C terminus and mediates the mono-ubiquitination of Bcl-2, which increases the steady-state levels of Bcl-2. PMID:32047033 Here, we demonstrate that VDAC1 can be either mono- or polyubiquitinated by Parkin in a PINK1-dependent manner. |
| GO:0006513 protein monoubiquitination | IMP PMID:24660806 Parkin is activated by PINK1-dependent phosphorylation of ub... | ACCEPT | Summary: Parkin monoubiquitinates substrates (e.g. Bcl-2, VDAC1). Reason: Directly shown. Supporting Evidence: PMID:20889974 Parkin directly binds to Bcl-2 via its C terminus and mediates the mono-ubiquitination of Bcl-2, which increases the steady-state levels of Bcl-2. PMID:32047033 Here, we demonstrate that VDAC1 can be either mono- or polyubiquitinated by Parkin in a PINK1-dependent manner. |
| GO:0006513 protein monoubiquitination | IMP PMID:32047033 Decision between mitophagy and apoptosis by Parkin via VDAC1... | ACCEPT | Summary: Parkin monoubiquitinates substrates (e.g. Bcl-2, VDAC1). Reason: Directly shown. Supporting Evidence: PMID:20889974 Parkin directly binds to Bcl-2 via its C terminus and mediates the mono-ubiquitination of Bcl-2, which increases the steady-state levels of Bcl-2. PMID:32047033 Here, we demonstrate that VDAC1 can be either mono- or polyubiquitinated by Parkin in a PINK1-dependent manner. |
| GO:0006979 response to oxidative stress | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Parkin protects against oxidative stress. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. |
| GO:0006986 response to unfolded protein | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Parkin is upregulated by, and protects against, unfolded protein stress. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:10973942 Furthermore, overexpression of Parkin, but not a set of mutants without the E3 activity, specifically suppressed unfolded protein stress-induced cell death. |
| GO:0007005 mitochondrion organization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Parkin maintains mitochondrial integrity (ortholog transfer). Reason: Broad term; the specific role is mitophagy. |
| GO:0007417 central nervous system development | TAS PMID:9560156 Mutations in the parkin gene cause autosomal recessive juven... | MARK AS OVER ANNOTATED | Summary: The gene-discovery paper identified PRKN mutations in AR-JP and its expression in brain. Reason: Parkin loss causes neurodegeneration, not a developmental defect; no evidence for a role in CNS development. Supporting Evidence: PMID:9560156 Mutations in the newly identified gene appear to be responsible for the pathogenesis of AR-JP, and we have therefore named the protein product 'Parkin'. |
| GO:0008013 beta-catenin binding | IDA PMID:19591802 Parkin protects dopaminergic neurons from excessive Wnt/beta... | KEEP AS NON CORE | Summary: Parkin binds and regulates the levels of beta-catenin. Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:19591802 We now show that Parkin, an E3 ubiquitin ligase linked to familial PD, regulates beta-catenin protein levels in vivo. |
| GO:0008021 synaptic vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Parkin reported associated with synaptic vesicles. Reason: Neuronal or synaptic location, consistent with Parkin being a cytosolic protein abundant in neurons. Not informative about its core function. Supporting Evidence: PMID:12925569 Parkin-mediated ubiquitination also enhances the turnover of sytXI. |
| GO:0008270 zinc ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Parkin RING0, RING1, IBR and RING2 domains coordinate structural zinc ions. Reason: Correct structural cofactor binding. Supporting Evidence: PMID:23626584 Parkin is a 52 kDa protein with an N-terminal ubiquitin-like (Ubl) domain followed by a 60 amino acid (a.a.) linker and four zinc-finger domains (Figure 1). |
| GO:0008270 zinc ion binding | TAS PMID:23626584 Structure and Function of Parkin, PINK1, and DJ-1, the Three... | ACCEPT | Summary: Parkin RING0, RING1, IBR and RING2 domains coordinate structural zinc ions. Reason: Correct structural cofactor binding. Supporting Evidence: PMID:23626584 Parkin is a 52 kDa protein with an N-terminal ubiquitin-like (Ubl) domain followed by a 60 amino acid (a.a.) linker and four zinc-finger domains (Figure 1). |
| GO:0008344 adult locomotory behavior | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Parkin-null animals show locomotor defects (ortholog transfer). Reason: Organism-level phenotype; non-core. |
| GO:0009410 response to xenobiotic stimulus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred response to xenobiotic stimulus. Reason: Ortholog-transferred (Ensembl Compara) annotation, most likely from a rodent phenotype or expression study. Parkin loss causes broad neuronal and mitochondrial dysfunction, so many readouts change secondarily. That does not show Parkin performs a step of this process. |
| GO:0009896 positive regulation of catabolic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Broad electronic term. Reason: Broad but not incorrect. |
| GO:0010498 proteasomal protein catabolic process | IMP PMID:19725078 Proteomic analysis of increased Parkin expression and its in... | KEEP AS NON CORE | Summary: Parkin overexpression altered levels of proteins in a 26S-proteasome-dependent manner. Reason: Consistent with E3 function but from a proteomic study; non-core. Supporting Evidence: PMID:19725078 This study provides further evidence for a role for Parkin in regulating mitochondrial activity within cells. |
| GO:0010506 regulation of autophagy | IDA PMID:20889974 Parkin mono-ubiquitinates Bcl-2 and regulates autophagy. | KEEP AS NON CORE | Summary: Parkin monoubiquitinates Bcl-2 and thereby modulates Bcl-2/Beclin 1 interaction and autophagy. Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:20889974 Our results provide evidence that parkin mono-ubiquitinates Bcl-2 and regulates autophagy via Bcl-2. |
| GO:0010628 positive regulation of gene expression | IMP PMID:19725078 Proteomic analysis of increased Parkin expression and its in... | MARK AS OVER ANNOTATED | Summary: Changes in protein levels after Parkin overexpression. Reason: Generic and indirect. Supporting Evidence: PMID:19725078 This study provides further evidence for a role for Parkin in regulating mitochondrial activity within cells. |
| GO:0010629 negative regulation of gene expression | IMP PMID:19725078 Proteomic analysis of increased Parkin expression and its in... | MARK AS OVER ANNOTATED | Summary: Changes in protein/mRNA levels after Parkin manipulation. Reason: Generic and indirect; Parkin acts post-translationally. Supporting Evidence: PMID:22314364 We demonstrate that loss of parkin in human midbrain DA neurons greatly increases the transcription of monoamine oxidases and oxidative stress, significantly reduces DA uptake and increases spontaneous DA release. |
| GO:0010629 negative regulation of gene expression | IMP PMID:22314364 Parkin controls dopamine utilization in human midbrain dopam... | MARK AS OVER ANNOTATED | Summary: Changes in protein/mRNA levels after Parkin manipulation. Reason: Generic and indirect; Parkin acts post-translationally. Supporting Evidence: PMID:22314364 We demonstrate that loss of parkin in human midbrain DA neurons greatly increases the transcription of monoamine oxidases and oxidative stress, significantly reduces DA uptake and increases spontaneous DA release. |
| GO:0010636 positive regulation of mitochondrial fusion | IMP PMID:23453807 The E3 ligase parkin maintains mitochondrial integrity by in... | KEEP AS NON CORE | Summary: Parkin-dependent linear ubiquitination of NEMO upregulates OPA1 transcription, maintaining mitochondrial integrity. Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:23453807 As a result, the mitochondrial guanosine triphosphatase OPA1 is transcriptionally upregulated via NF-ΞΊB-responsive promoter elements for maintenance of mitochondrial integrity and protection from stress-induced cell death. |
| GO:0010637 negative regulation of mitochondrial fusion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Parkin ubiquitinates mitofusins and targets them for degradation, limiting fusion of damaged mitochondria. Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:20871098 The ubiquitination of several mitochondrial proteins, including mitofusin 1 and mitofusin 2, were detected within 3 h of CCCP treatment. PMID:24898855 MUL1 acts in parallel to the PINK1/parkin pathway on a shared target mitofusin to maintain mitochondrial integrity. |
| GO:0010821 regulation of mitochondrion organization | IDA PMID:21113145 Parkin is transcriptionally regulated by ATF4: evidence for ... | KEEP AS NON CORE | Summary: Parkin regulates mitochondrial organization (e.g. preventing ER-stress-induced mitochondrial damage). Reason: Broad; the specific role is mitophagy. Supporting Evidence: PMID:21113145 Vice versa, ER stress results in mitochondrial damage, which can be prevented by parkin. |
| GO:0010821 regulation of mitochondrion organization | IGI PMID:19279012 Loss of PINK1 function promotes mitophagy through effects on... | KEEP AS NON CORE | Summary: Parkin regulates mitochondrial organization (e.g. preventing ER-stress-induced mitochondrial damage). Reason: Broad; the specific role is mitophagy. Supporting Evidence: PMID:21113145 Vice versa, ER stress results in mitochondrial damage, which can be prevented by parkin. |
| GO:0010821 regulation of mitochondrion organization | NAS PMID:20890124 p62/SQSTM1 is required for Parkin-induced mitochondrial clus... | KEEP AS NON CORE | Summary: Parkin regulates mitochondrial organization (e.g. preventing ER-stress-induced mitochondrial damage). Reason: Broad; the specific role is mitophagy. Supporting Evidence: PMID:21113145 Vice versa, ER stress results in mitochondrial damage, which can be prevented by parkin. |
| GO:0010906 regulation of glucose metabolic process | TAS PMID:23626584 Structure and Function of Parkin, PINK1, and DJ-1, the Three... | MARK AS OVER ANNOTATED | Summary: Review statement on Parkin and glucose metabolism. Reason: Speculative and indirect. |
| GO:0010918 positive regulation of mitochondrial membrane potential | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred positive regulation of mitochondrial membrane potential. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. |
| GO:0010994 free ubiquitin chain polymerization | IMP PMID:24660806 Parkin is activated by PINK1-dependent phosphorylation of ub... | ACCEPT | Summary: Phospho-ubiquitin-activated Parkin catalyses free ubiquitin chain formation in vitro. Reason: Direct readout of activated Parkin E3 activity. Supporting Evidence: PMID:24660806 We undertook a series of experiments that provide striking evidence that Ser65-phosphorylated ubiquitin (ubiquitinPhospho-Ser65) functions as a critical activator of Parkin. |
| GO:0014059 regulation of dopamine secretion | TAS PMID:21563316 Synaptic vesicle trafficking and Parkinson's disease. | MARK AS OVER ANNOTATED | Summary: Review-based statement about PD genes and dopamine release. Reason: Speculative review statement; better captured by the IMP-based neurotransmitter annotations. |
| GO:0014069 postsynaptic density | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Parkin reported at postsynaptic densities (ortholog transfer). Reason: Neuronal or synaptic location, consistent with Parkin being a cytosolic protein abundant in neurons. Not informative about its core function. |
| GO:0014069 postsynaptic density | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Parkin reported at postsynaptic densities (ortholog transfer). Reason: Neuronal or synaptic location, consistent with Parkin being a cytosolic protein abundant in neurons. Not informative about its core function. |
| GO:0014850 response to muscle activity | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred response to muscle activity. Reason: Ortholog-transferred (Ensembl Compara) annotation, most likely from a rodent phenotype or expression study. Parkin loss causes broad neuronal and mitochondrial dysfunction, so many readouts change secondarily. That does not show Parkin performs a step of this process. |
| GO:0015631 tubulin binding | IPI PMID:21753002 Parkin interacts with Ambra1 to induce mitophagy. | MARK AS OVER ANNOTATED | Summary: Tubulin detected among Parkin co-immunoprecipitants in a study focused on Ambra1. Reason: Possibly genuine (Parkin has been reported to bind microtubules), but in this study it is an incidental interactor and not an informative function. Supporting Evidence: PMID:21753002 These data identify interaction of Parkin with Ambra1 as a key mechanism for induction of the final clearance step of Parkin-mediated mitophagy. |
| GO:0015631 tubulin binding | IPI PMID:21753002 Parkin interacts with Ambra1 to induce mitophagy. | MARK AS OVER ANNOTATED | Summary: Tubulin detected among Parkin co-immunoprecipitants in a study focused on Ambra1. Reason: Possibly genuine (Parkin has been reported to bind microtubules), but in this study it is an incidental interactor and not an informative function. Supporting Evidence: PMID:21753002 These data identify interaction of Parkin with Ambra1 as a key mechanism for induction of the final clearance step of Parkin-mediated mitophagy. |
| GO:0016235 aggresome | IDA PMID:14645198 Parkin is recruited into aggresomes in a stress-specific man... | KEEP AS NON CORE | Summary: Endogenous Parkin is recruited to stress-induced aggresomes. Reason: Experimentally supported location; non-core. Supporting Evidence: PMID:14645198 In human SH-SY5Y neuroblastoma cells we observe that endogenous parkin is present in aggresomes induced by a variety of stresses including dopamine, proteosome inhibition and a pro-apoptopic stimulus. |
| GO:0016236 macroautophagy | TAS Reactome:R-HSA-5205685 | ACCEPT | Summary: PINK1/Parkin mitophagy is a selective macroautophagy. Reason: Correct parent of the core process. Supporting Evidence: PMID:19029340 After recruitment, Parkin mediates the engulfment of mitochondria by autophagosomes and the selective elimination of impaired mitochondria. |
| GO:0016567 protein ubiquitination | IDA PMID:10973942 Parkin suppresses unfolded protein stress-induced cell death... | ACCEPT | Summary: Parkin is an RBR E3 ubiquitin ligase that ubiquitinates numerous substrates, including outer-membrane proteins of damaged mitochondria. Reason: Core process. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:20871098 The ubiquitination of several mitochondrial proteins, including mitofusin 1 and mitofusin 2, were detected within 3 h of CCCP treatment. |
| GO:0016567 protein ubiquitination | IDA PMID:11439185 An unfolded putative transmembrane polypeptide, which can le... | ACCEPT | Summary: Parkin is an RBR E3 ubiquitin ligase that ubiquitinates numerous substrates, including outer-membrane proteins of damaged mitochondria. Reason: Core process. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:20871098 The ubiquitination of several mitochondrial proteins, including mitofusin 1 and mitofusin 2, were detected within 3 h of CCCP treatment. |
| GO:0016567 protein ubiquitination | IDA PMID:12628165 Parkin is a component of an SCF-like ubiquitin ligase comple... | ACCEPT | Summary: Parkin is an RBR E3 ubiquitin ligase that ubiquitinates numerous substrates, including outer-membrane proteins of damaged mitochondria. Reason: Core process. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:20871098 The ubiquitination of several mitochondrial proteins, including mitofusin 1 and mitofusin 2, were detected within 3 h of CCCP treatment. |
| GO:0016567 protein ubiquitination | IDA PMID:17314283 Parkin mediates neuroprotection through activation of Ikappa... | ACCEPT | Summary: Parkin is an RBR E3 ubiquitin ligase that ubiquitinates numerous substrates, including outer-membrane proteins of damaged mitochondria. Reason: Core process. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:20871098 The ubiquitination of several mitochondrial proteins, including mitofusin 1 and mitofusin 2, were detected within 3 h of CCCP treatment. |
| GO:0016567 protein ubiquitination | IEA GO_REF:0000120 | ACCEPT | Summary: Parkin is an RBR E3 ubiquitin ligase that ubiquitinates numerous substrates, including outer-membrane proteins of damaged mitochondria. Reason: Core process. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:20871098 The ubiquitination of several mitochondrial proteins, including mitofusin 1 and mitofusin 2, were detected within 3 h of CCCP treatment. |
| GO:0016567 protein ubiquitination | IMP PMID:23933751 The Parkinson's disease-linked proteins Fbxo7 and Parkin int... | ACCEPT | Summary: Parkin is an RBR E3 ubiquitin ligase that ubiquitinates numerous substrates, including outer-membrane proteins of damaged mitochondria. Reason: Core process. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:20871098 The ubiquitination of several mitochondrial proteins, including mitofusin 1 and mitofusin 2, were detected within 3 h of CCCP treatment. |
| GO:0016567 protein ubiquitination | IMP PMID:26911690 Parkin Modulates Endosomal Organization and Function of the ... | ACCEPT | Summary: Parkin is an RBR E3 ubiquitin ligase that ubiquitinates numerous substrates, including outer-membrane proteins of damaged mitochondria. Reason: Core process. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:20871098 The ubiquitination of several mitochondrial proteins, including mitofusin 1 and mitofusin 2, were detected within 3 h of CCCP treatment. |
| GO:0016567 protein ubiquitination | IMP PMID:29311685 Synaptotagmin-11 is a critical mediator of parkin-linked neu... | ACCEPT | Summary: Parkin is an RBR E3 ubiquitin ligase that ubiquitinates numerous substrates, including outer-membrane proteins of damaged mitochondria. Reason: Core process. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:20871098 The ubiquitination of several mitochondrial proteins, including mitofusin 1 and mitofusin 2, were detected within 3 h of CCCP treatment. |
| GO:0016579 protein deubiquitination | TAS Reactome:R-HSA-5688426 | REMOVE | Summary: Reactome places Parkin in the "deubiquitination" pathway because it is a substrate of DUBs (e.g. USP8, USP30 counteract it). Reason: Parkin is an E3 ligase and does not carry out deubiquitination. Pathway membership as a DUB substrate is not participation in the process. Supporting Evidence: PMID:25621951 We find that mitochondrial damage stimulates parkin to assemble Lys 6, Lys 11 and Lys 63 chains on mitochondria, and that USP30 is a ubiquitin-specific deubiquitylase with a strong preference for cleaving Lys 6- and Lys 11-linked multimers. |
| GO:0016607 nuclear speck | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Nuclear speck staining from Human Protein Atlas immunofluorescence. Reason: Minor and unexplained location; non-core. |
| GO:0017124 SH3 domain binding | TAS PMID:23626584 Structure and Function of Parkin, PINK1, and DJ-1, the Three... | KEEP AS NON CORE | Summary: The Parkin Ubl domain binds SH3 domains of endophilin-A, linking Parkin to synaptic vesicle endocytosis. Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:23626584 Parkin is a 52 kDa protein with an N-terminal ubiquitin-like (Ubl) domain followed by a 60 amino acid (a.a.) linker and four zinc-finger domains (Figure 1). |
| GO:0019005 SCF ubiquitin ligase complex | IDA NOT PMID:12628165 Parkin is a component of an SCF-like ubiquitin ligase comple... | ACCEPT | Summary: NOT annotation: the Parkin-hSel-10-Cul1 complex is described as SCF-like, with Parkin rather than a canonical SCF RING subunit supplying the ligase activity. Reason: The curator negated canonical SCF membership. This agrees with the paper, which describes an SCF-like complex in which Parkin supplies the ligase activity. Supporting Evidence: PMID:12628165 Here we show that parkin functions in a multiprotein ubiquitin ligase complex that includes the F-box/WD repeat protein hSel-10 and Cullin-1. |
| GO:0019899 enzyme binding | IPI PMID:19725078 Proteomic analysis of increased Parkin expression and its in... | MARK AS OVER ANNOTATED | Summary: Interactors identified by tandem affinity purification/MS. Reason: Generic binding from a proteomic screen; uninformative. Supporting Evidence: PMID:19725078 This study provides further evidence for a role for Parkin in regulating mitochondrial activity within cells. |
| GO:0019900 kinase binding | IPI PMID:17512523 Parkin interacts with LIM Kinase 1 and reduces its cofilin-p... | KEEP AS NON CORE | Summary: Parkin binds kinases including PINK1 and LIMK1. Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:18957282 In detail, Parkin phosphorylation by PINK1 on its linker region promotes its mitochondrial translocation, and the RING1 domain of Parkin is critical for this occurrence. |
| GO:0019900 kinase binding | IPI PMID:19229105 Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex p... | KEEP AS NON CORE | Summary: Parkin binds kinases including PINK1 and LIMK1. Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:18957282 In detail, Parkin phosphorylation by PINK1 on its linker region promotes its mitochondrial translocation, and the RING1 domain of Parkin is critical for this occurrence. |
| GO:0019900 kinase binding | IPI PMID:19880420 Phosphorylation of parkin by Parkinson disease-linked kinase... | KEEP AS NON CORE | Summary: Parkin binds kinases including PINK1 and LIMK1. Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:18957282 In detail, Parkin phosphorylation by PINK1 on its linker region promotes its mitochondrial translocation, and the RING1 domain of Parkin is critical for this occurrence. |
| GO:0019900 kinase binding | IPI PMID:24187134 Identification of the ubiquitin-like domain of midnolin as a... | KEEP AS NON CORE | Summary: Parkin binds kinases including PINK1 and LIMK1. Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:18957282 In detail, Parkin phosphorylation by PINK1 on its linker region promotes its mitochondrial translocation, and the RING1 domain of Parkin is critical for this occurrence. |
| GO:0019901 protein kinase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Parkin binds the kinase PINK1, which phosphorylates and activates it. Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:18957282 In detail, Parkin phosphorylation by PINK1 on its linker region promotes its mitochondrial translocation, and the RING1 domain of Parkin is critical for this occurrence. |
| GO:0019901 protein kinase binding | IPI PMID:20798600 The PINK1/Parkin-mediated mitophagy is compromised by PD-ass... | KEEP AS NON CORE | Summary: Parkin binds the kinase PINK1, which phosphorylates and activates it. Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:18957282 In detail, Parkin phosphorylation by PINK1 on its linker region promotes its mitochondrial translocation, and the RING1 domain of Parkin is critical for this occurrence. |
| GO:0022603 regulation of anatomical structure morphogenesis | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Broad electronic morphogenesis term. Reason: No evidence that Parkin regulates anatomical structure morphogenesis. |
| GO:0030163 protein catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: Parkin promotes degradation of its ubiquitinated substrates. Reason: Correct broad parent. |
| GO:0030165 PDZ domain binding | IPI PMID:17512523 Parkin interacts with LIM Kinase 1 and reduces its cofilin-p... | KEEP AS NON CORE | Summary: Parkin interacts with PDZ-domain proteins (e.g. LIMK1, CASK) via its C terminus. Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:17512523 Additionally, in simian kidney-derived COS-7 cells, parkin-over-expression reduced LIMK1-induced actin filament accumulation. |
| GO:0030424 axon | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred axon location. Reason: Neuronal or synaptic location, consistent with Parkin being a cytosolic protein abundant in neurons. Not informative about its core function. |
| GO:0030544 Hsp70 protein binding | IPI PMID:12150907 CHIP is associated with Parkin, a gene responsible for famil... | KEEP AS NON CORE | Summary: Parkin forms complexes with Hsp70 (and CHIP), which modulate its E3 activity towards misfolded substrates. Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:12150907 CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. |
| GO:0030544 Hsp70 protein binding | IPI PMID:21753002 Parkin interacts with Ambra1 to induce mitophagy. | KEEP AS NON CORE | Summary: Parkin forms complexes with Hsp70 (and CHIP), which modulate its E3 activity towards misfolded substrates. Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:12150907 CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. |
| GO:0030672 synaptic vesicle membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred synaptic vesicle membrane location. Reason: Neuronal or synaptic location, consistent with Parkin being a cytosolic protein abundant in neurons. Not informative about its core function. |
| GO:0031072 heat shock protein binding | IPI PMID:12150907 CHIP is associated with Parkin, a gene responsible for famil... | KEEP AS NON CORE | Summary: Parkin associates with Hsp70 in a CHIP-containing complex. Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:12150907 CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. |
| GO:0031396 regulation of protein ubiquitination | IGI PMID:23212910 Phosphatase and tensin homolog (PTEN)-induced putative kinas... | KEEP AS NON CORE | Summary: PINK1-dependent regulation of Parkin-mediated ubiquitination. Reason: Parkin is itself the E3; "regulation of protein ubiquitination" fits its activators better. Non-core. Supporting Evidence: PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. |
| GO:0031396 regulation of protein ubiquitination | IMP PMID:20871098 Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/par... | KEEP AS NON CORE | Summary: PINK1-dependent regulation of Parkin-mediated ubiquitination. Reason: Parkin is itself the E3; "regulation of protein ubiquitination" fits its activators better. Non-core. Supporting Evidence: PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. |
| GO:0031624 ubiquitin conjugating enzyme binding | IBA GO_REF:0000033 | ACCEPT | Summary: Parkin binds E2 ubiquitin-conjugating enzymes (UbcH7/UBE2L3, UbcH8) through its RING1 domain. Reason: Intrinsic to its RBR E3 mechanism. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:21532592 We show that RBRs function like RING/HECT hybrids: they bind E2s via a RING domain, but transfer Ub through an obligate thioester-linked Ub (denoted βΌUb), requiring a conserved cysteine residue in RING2. |
| GO:0031624 ubiquitin conjugating enzyme binding | IDA PMID:10973942 Parkin suppresses unfolded protein stress-induced cell death... | ACCEPT | Summary: Parkin binds E2 ubiquitin-conjugating enzymes (UbcH7/UBE2L3, UbcH8) through its RING1 domain. Reason: Intrinsic to its RBR E3 mechanism. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:21532592 We show that RBRs function like RING/HECT hybrids: they bind E2s via a RING domain, but transfer Ub through an obligate thioester-linked Ub (denoted βΌUb), requiring a conserved cysteine residue in RING2. |
| GO:0031624 ubiquitin conjugating enzyme binding | IPI PMID:11439185 An unfolded putative transmembrane polypeptide, which can le... | ACCEPT | Summary: Parkin binds E2 ubiquitin-conjugating enzymes (UbcH7/UBE2L3, UbcH8) through its RING1 domain. Reason: Intrinsic to its RBR E3 mechanism. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:21532592 We show that RBRs function like RING/HECT hybrids: they bind E2s via a RING domain, but transfer Ub through an obligate thioester-linked Ub (denoted βΌUb), requiring a conserved cysteine residue in RING2. |
| GO:0031624 ubiquitin conjugating enzyme binding | IPI PMID:11439185 An unfolded putative transmembrane polypeptide, which can le... | ACCEPT | Summary: Parkin binds E2 ubiquitin-conjugating enzymes (UbcH7/UBE2L3, UbcH8) through its RING1 domain. Reason: Intrinsic to its RBR E3 mechanism. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:21532592 We show that RBRs function like RING/HECT hybrids: they bind E2s via a RING domain, but transfer Ub through an obligate thioester-linked Ub (denoted βΌUb), requiring a conserved cysteine residue in RING2. |
| GO:0031624 ubiquitin conjugating enzyme binding | IPI PMID:12628165 Parkin is a component of an SCF-like ubiquitin ligase comple... | ACCEPT | Summary: Parkin binds E2 ubiquitin-conjugating enzymes (UbcH7/UBE2L3, UbcH8) through its RING1 domain. Reason: Intrinsic to its RBR E3 mechanism. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:21532592 We show that RBRs function like RING/HECT hybrids: they bind E2s via a RING domain, but transfer Ub through an obligate thioester-linked Ub (denoted βΌUb), requiring a conserved cysteine residue in RING2. |
| GO:0031625 ubiquitin protein ligase binding | IMP PMID:24751536 PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquit... | KEEP AS NON CORE | Summary: Parkin interacts with other E3 ligases (e.g. CHIP, Nrdp1, Fbxo7, LUBAC components). Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:12150907 CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:12150907 CHIP is associated with Parkin, a gene responsible for famil... | KEEP AS NON CORE | Summary: Parkin interacts with other E3 ligases (e.g. CHIP, Nrdp1, Fbxo7, LUBAC components). Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:12150907 CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:21532592 UBCH7 reactivity profile reveals parkin and HHARI to be RING... | KEEP AS NON CORE | Summary: Parkin interacts with other E3 ligases (e.g. CHIP, Nrdp1, Fbxo7, LUBAC components). Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:12150907 CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:23453807 The E3 ligase parkin maintains mitochondrial integrity by in... | KEEP AS NON CORE | Summary: Parkin interacts with other E3 ligases (e.g. CHIP, Nrdp1, Fbxo7, LUBAC components). Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:12150907 CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. |
| GO:0031647 regulation of protein stability | IMP PMID:26911690 Parkin Modulates Endosomal Organization and Function of the ... | KEEP AS NON CORE | Summary: Parkin regulates Rab7 levels and activity via K38 ubiquitination. Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:26911690 To elucidate the molecular mechanism of these alterations in the endocytic pathway in Parkin-deficient cells, we found that Parkin regulates the levels and activity of Rab7 by promoting its ubiquitination on lysine 38 residue. |
| GO:0031648 protein destabilization | IDA PMID:19591802 Parkin protects dopaminergic neurons from excessive Wnt/beta... | KEEP AS NON CORE | Summary: Parkin destabilizes substrates such as beta-catenin and synaptotagmin-11. Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:19591802 We now show that Parkin, an E3 ubiquitin ligase linked to familial PD, regulates beta-catenin protein levels in vivo. PMID:29311685 Furthermore, parkin deficiency induces synaptotagmin-11 accumulation and PD-like neurotoxicity in mouse models, which is reversed by SYT11 knockdown in the SNpc or knockout of SYT11 restricted to dopaminergic neurons. |
| GO:0031648 protein destabilization | IDA PMID:29311685 Synaptotagmin-11 is a critical mediator of parkin-linked neu... | KEEP AS NON CORE | Summary: Parkin destabilizes substrates such as beta-catenin and synaptotagmin-11. Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:19591802 We now show that Parkin, an E3 ubiquitin ligase linked to familial PD, regulates beta-catenin protein levels in vivo. PMID:29311685 Furthermore, parkin deficiency induces synaptotagmin-11 accumulation and PD-like neurotoxicity in mouse models, which is reversed by SYT11 knockdown in the SNpc or knockout of SYT11 restricted to dopaminergic neurons. |
| GO:0031648 protein destabilization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Parkin destabilizes substrates such as beta-catenin and synaptotagmin-11. Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:19591802 We now show that Parkin, an E3 ubiquitin ligase linked to familial PD, regulates beta-catenin protein levels in vivo. PMID:29311685 Furthermore, parkin deficiency induces synaptotagmin-11 accumulation and PD-like neurotoxicity in mouse models, which is reversed by SYT11 knockdown in the SNpc or knockout of SYT11 restricted to dopaminergic neurons. |
| GO:0032232 negative regulation of actin filament bundle assembly | IDA PMID:17512523 Parkin interacts with LIM Kinase 1 and reduces its cofilin-p... | KEEP AS NON CORE | Summary: Parkin overexpression reduced LIMK1-induced actin filament accumulation. Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:17512523 Additionally, in simian kidney-derived COS-7 cells, parkin-over-expression reduced LIMK1-induced actin filament accumulation. |
| GO:0032368 regulation of lipid transport | TAS PMID:23626584 Structure and Function of Parkin, PINK1, and DJ-1, the Three... | MARK AS OVER ANNOTATED | Summary: Review statement on Parkin and lipid transport. Reason: Speculative and indirect. |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: Parkin promotes proteasomal, ubiquitin-dependent degradation of its substrates (e.g. Miro, mitofusins, PARIS). Reason: Direct consequence of Parkin E3 ligase activity. Supporting Evidence: PMID:22078885 The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner. PMID:21376232 whose levels are regulated by the ubiquitin proteasome system via binding to and ubiquitination by the E3 ubiquitin ligase, parkin |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | TAS PMID:24115276 The regulation and deregulation of Wnt signaling by PARK gen... | ACCEPT | Summary: Parkin promotes proteasomal, ubiquitin-dependent degradation of its substrates (e.g. Miro, mitofusins, PARIS). Reason: Direct consequence of Parkin E3 ligase activity. Supporting Evidence: PMID:22078885 The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner. PMID:21376232 whose levels are regulated by the ubiquitin proteasome system via binding to and ubiquitination by the E3 ubiquitin ligase, parkin |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Parkin is found in various protein complexes. Reason: Uninformative broad term. |
| GO:0033132 negative regulation of glucokinase activity | IDA PMID:24187134 Identification of the ubiquitin-like domain of midnolin as a... | MARK AS OVER ANNOTATED | Summary: In MIN6 cells, Parkin overexpression had only some effect on glucokinase activity. Reason: A weak overexpression effect in a study centred on midnolin; not a demonstrated Parkin function. Supporting Evidence: PMID:24187134 Overexpression of parkin, an ubiquitin E3 ligase exhibiting an ubiquitin-like domain with high homology to the identified, diminished insulin secretion in MIN6 cells but had only some effect on glucokinase activity. |
| GO:0034599 cellular response to oxidative stress | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Parkin protects against oxidative stress (e.g. it suppresses Nrdp1-induced ROS). Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:18541373 In addition, we demonstrated that overexpression of Nrdp1 increased the production of reactive oxygen species (ROS), which was abrogated by co-expression of Parkin. |
| GO:0034599 cellular response to oxidative stress | TAS PMID:24252804 The role of oxidative stress in Parkinson's disease. | KEEP AS NON CORE | Summary: Parkin protects against oxidative stress (e.g. it suppresses Nrdp1-induced ROS). Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:18541373 In addition, we demonstrated that overexpression of Nrdp1 increased the production of reactive oxygen species (ROS), which was abrogated by co-expression of Parkin. |
| GO:0034620 cellular response to unfolded protein | TAS PMID:18221368 Biochemical aspects of the neuroprotective mechanism of PTEN... | KEEP AS NON CORE | Summary: Parkin is upregulated by, and protects against, unfolded protein stress. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:10973942 Furthermore, overexpression of Parkin, but not a set of mutants without the E3 activity, specifically suppressed unfolded protein stress-induced cell death. |
| GO:0034976 response to endoplasmic reticulum stress | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Parkin is induced by ER stress (via ATF4) and protects against ER-stress-induced mitochondrial damage. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:21113145 Vice versa, ER stress results in mitochondrial damage, which can be prevented by parkin. |
| GO:0034976 response to endoplasmic reticulum stress | IMP PMID:21113145 Parkin is transcriptionally regulated by ATF4: evidence for ... | KEEP AS NON CORE | Summary: Parkin is induced by ER stress (via ATF4) and protects against ER-stress-induced mitochondrial damage. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:21113145 Vice versa, ER stress results in mitochondrial damage, which can be prevented by parkin. |
| GO:0035519 protein K29-linked ubiquitination | TAS PMID:23626584 Structure and Function of Parkin, PINK1, and DJ-1, the Three... | KEEP AS NON CORE | Summary: Parkin can form K29-linked chains in cells (review). Reason: Less-established linkage type, supported only by a review statement. Supporting Evidence: PMID:23626584 (2011) showed that Parkin can form K6, K27, K29, and K63 chains in cells, and that it can form polyubiquitin chains that are deconjugated by ataxin-3 in vitro (Durcan et al., 2012). |
| GO:0035774 positive regulation of insulin secretion involved in cellular response to glucose stimulus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred positive regulation of glucose-stimulated insulin secretion. Reason: Ortholog-transferred (Ensembl Compara) annotation, most likely from a rodent phenotype or expression study. Parkin loss causes broad neuronal and mitochondrial dysfunction, so many readouts change secondarily. That does not show Parkin performs a step of this process. |
| GO:0036503 ERAD quality control pathway | NAS PMID:10973942 Parkin suppresses unfolded protein stress-induced cell death... | KEEP AS NON CORE | Summary: Parkin ubiquitinates misfolded ER-derived proteins (e.g. Pael-R) with ER-resident E2s and protects against unfolded protein stress. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:11439185 Parkin specifically ubiquitinates this receptor in the presence of ubiquitin-conjugating enzymes resident in the endoplasmic reticulum and promotes the degradation of insoluble Pael receptor, resulting in suppression of the cell death induced by Pael receptor overexpression. |
| GO:0042053 regulation of dopamine metabolic process | IMP PMID:22314364 Parkin controls dopamine utilization in human midbrain dopam... | KEEP AS NON CORE | Summary: Loss of Parkin in human iPSC-derived midbrain DA neurons increases MAO transcription and dopamine oxidation. Reason: Experimental, human-neuron-specific, likely indirect; non-core. Supporting Evidence: PMID:22314364 We demonstrate that loss of parkin in human midbrain DA neurons greatly increases the transcription of monoamine oxidases and oxidative stress, significantly reduces DA uptake and increases spontaneous DA release. |
| GO:0042417 dopamine metabolic process | TAS PMID:23626584 Structure and Function of Parkin, PINK1, and DJ-1, the Three... | MARK AS OVER ANNOTATED | Summary: Review statement linking Parkin to dopamine metabolism. Reason: Parkin loss alters dopamine handling indirectly; it is not an enzyme of dopamine metabolism. Supporting Evidence: PMID:22314364 We demonstrate that loss of parkin in human midbrain DA neurons greatly increases the transcription of monoamine oxidases and oxidative stress, significantly reduces DA uptake and increases spontaneous DA release. |
| GO:0042802 identical protein binding | IPI PMID:21694720 Autoregulation of Parkin activity through its ubiquitin-like... | MARK AS OVER ANNOTATED | Summary: The Parkin Ubl domain binds the C-terminal region of Parkin to autoinhibit it. Reason: This is mainly intramolecular autoinhibition, not a functional homo-oligomer, so identical protein binding is not informative. Supporting Evidence: PMID:21694720 We now demonstrate that the ubiquitin-like domain of Parkin functions to inhibit its autoubiquitination. |
| GO:0042826 histone deacetylase binding | IPI PMID:21753002 Parkin interacts with Ambra1 to induce mitophagy. | MARK AS OVER ANNOTATED | Summary: HDAC6 detected among Parkin interactors in a study focused on Ambra1. Reason: Incidental interaction; not an informative Parkin function. Supporting Evidence: PMID:21753002 These data identify interaction of Parkin with Ambra1 as a key mechanism for induction of the final clearance step of Parkin-mediated mitophagy. |
| GO:0043005 neuron projection | IDA PMID:12925569 The autosomal recessive juvenile Parkinson disease gene prod... | KEEP AS NON CORE | Summary: Parkin detected in neuronal processes. Reason: Neuronal or synaptic location, consistent with Parkin being a cytosolic protein abundant in neurons. Not informative about its core function. |
| GO:0043005 neuron projection | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Parkin detected in neuronal processes. Reason: Neuronal or synaptic location, consistent with Parkin being a cytosolic protein abundant in neurons. Not informative about its core function. |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred neuronal cell body location. Reason: Neuronal or synaptic location, consistent with Parkin being a cytosolic protein abundant in neurons. Not informative about its core function. |
| GO:0043065 positive regulation of apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Parkin can promote apoptosis in some contexts (e.g. Mcl-1 degradation after severe damage). Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IDA PMID:17314283 Parkin mediates neuroprotection through activation of Ikappa... | KEEP AS NON CORE | Summary: Parkin promotes K63 and linear ubiquitination of NEMO/TRAF2 and activates canonical NF-kappaB signalling. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:17314283 Finally, we present evidence that parkin interacts with and promotes degradation-independent ubiquitylation of IKKgamma/NEMO (NF-kappaB essential modifier) and TRAF2 [TNF (tumor necrosis factor) receptor-associated factor 2], two critical components of the NF-kappaB pathway. PMID:23453807 Under cellular stress, parkin is recruited to the linear ubiquitin assembly complex and increases linear ubiquitination of NF-ΞΊB essential modulator (NEMO), which is essential for canonical NF-ΞΊB signaling. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IDA PMID:19880420 Phosphorylation of parkin by Parkinson disease-linked kinase... | KEEP AS NON CORE | Summary: Parkin promotes K63 and linear ubiquitination of NEMO/TRAF2 and activates canonical NF-kappaB signalling. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:17314283 Finally, we present evidence that parkin interacts with and promotes degradation-independent ubiquitylation of IKKgamma/NEMO (NF-kappaB essential modifier) and TRAF2 [TNF (tumor necrosis factor) receptor-associated factor 2], two critical components of the NF-kappaB pathway. PMID:23453807 Under cellular stress, parkin is recruited to the linear ubiquitin assembly complex and increases linear ubiquitination of NF-ΞΊB essential modulator (NEMO), which is essential for canonical NF-ΞΊB signaling. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IMP PMID:23453807 The E3 ligase parkin maintains mitochondrial integrity by in... | KEEP AS NON CORE | Summary: Parkin promotes K63 and linear ubiquitination of NEMO/TRAF2 and activates canonical NF-kappaB signalling. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:17314283 Finally, we present evidence that parkin interacts with and promotes degradation-independent ubiquitylation of IKKgamma/NEMO (NF-kappaB essential modifier) and TRAF2 [TNF (tumor necrosis factor) receptor-associated factor 2], two critical components of the NF-kappaB pathway. PMID:23453807 Under cellular stress, parkin is recruited to the linear ubiquitin assembly complex and increases linear ubiquitination of NF-ΞΊB essential modulator (NEMO), which is essential for canonical NF-ΞΊB signaling. |
| GO:0043130 ubiquitin binding | IDA PMID:24784582 Ubiquitin is phosphorylated by PINK1 to activate parkin. | ACCEPT | Summary: Parkin binds Ser65-phosphorylated ubiquitin, which recruits it to mitochondria and allosterically activates it. Reason: Phospho-ubiquitin binding is a central part of the Parkin activation mechanism. Supporting Evidence: PMID:24784582 PINK1 is a Ser/Thr kinase that specifically accumulates on depolarized mitochondria, whereas parkin is an E3 ubiquitin ligase that catalyses ubiquitin transfer to mitochondrial substrates. PMID:24660806 We undertook a series of experiments that provide striking evidence that Ser65-phosphorylated ubiquitin (ubiquitinPhospho-Ser65) functions as a critical activator of Parkin. |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IDA PMID:11439185 An unfolded putative transmembrane polypeptide, which can le... | ACCEPT | Summary: Parkin ubiquitinates substrates (e.g. Pael-R, PARIS) for proteasomal degradation. Reason: Direct consequence of Parkin E3 ligase activity. Supporting Evidence: PMID:11439185 Parkin specifically ubiquitinates this receptor in the presence of ubiquitin-conjugating enzymes resident in the endoplasmic reticulum and promotes the degradation of insoluble Pael receptor, resulting in suppression of the cell death induced by Pael receptor overexpression. PMID:21376232 whose levels are regulated by the ubiquitin proteasome system via binding to and ubiquitination by the E3 ubiquitin ligase, parkin |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IDA PMID:21376232 PARIS (ZNF746) repression of PGC-1Ξ± contributes to neurodege... | ACCEPT | Summary: Parkin ubiquitinates substrates (e.g. Pael-R, PARIS) for proteasomal degradation. Reason: Direct consequence of Parkin E3 ligase activity. Supporting Evidence: PMID:11439185 Parkin specifically ubiquitinates this receptor in the presence of ubiquitin-conjugating enzymes resident in the endoplasmic reticulum and promotes the degradation of insoluble Pael receptor, resulting in suppression of the cell death induced by Pael receptor overexpression. PMID:21376232 whose levels are regulated by the ubiquitin proteasome system via binding to and ubiquitination by the E3 ubiquitin ligase, parkin |
| GO:0043195 terminal bouton | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred terminal bouton location. Reason: Neuronal or synaptic location, consistent with Parkin being a cytosolic protein abundant in neurons. Not informative about its core function. |
| GO:0043274 phospholipase binding | IPI PMID:19725078 Proteomic analysis of increased Parkin expression and its in... | MARK AS OVER ANNOTATED | Summary: Interactors identified by tandem affinity purification/MS. Reason: Generic binding from a proteomic screen; uninformative. Supporting Evidence: PMID:19725078 This study provides further evidence for a role for Parkin in regulating mitochondrial activity within cells. |
| GO:0043524 negative regulation of neuron apoptotic process | IDA PMID:12628165 Parkin is a component of an SCF-like ubiquitin ligase comple... | KEEP AS NON CORE | Summary: Parkin protects neurons from apoptosis (e.g. kainate excitotoxicity via cyclin E, p53 repression). Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:12628165 Furthermore, parkin overexpression attenuates the accumulation of cyclin E in toxin-treated primary neurons, including midbrain dopamine neurons, and protects them from apoptosis. |
| 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: Parkin protects neurons from apoptosis (e.g. kainate excitotoxicity via cyclin E, p53 repression). Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:12628165 Furthermore, parkin overexpression attenuates the accumulation of cyclin E in toxin-treated primary neurons, including midbrain dopamine neurons, and protects them from apoptosis. |
| GO:0043524 negative regulation of neuron apoptotic process | IDA PMID:23985028 S-Nitrosylation of parkin as a novel regulator of p53-mediat... | KEEP AS NON CORE | Summary: Parkin protects neurons from apoptosis (e.g. kainate excitotoxicity via cyclin E, p53 repression). Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:12628165 Furthermore, parkin overexpression attenuates the accumulation of cyclin E in toxin-treated primary neurons, including midbrain dopamine neurons, and protects them from apoptosis. |
| GO:0043524 negative regulation of neuron apoptotic process | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Parkin protects neurons from apoptosis (e.g. kainate excitotoxicity via cyclin E, p53 repression). Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:12628165 Furthermore, parkin overexpression attenuates the accumulation of cyclin E in toxin-treated primary neurons, including midbrain dopamine neurons, and protects them from apoptosis. |
| GO:0043653 mitochondrial fragmentation involved in apoptotic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred mitochondrial fragmentation in apoptosis. Reason: Ortholog-transferred (Ensembl Compara) annotation, most likely from a rodent phenotype or expression study. Parkin loss causes broad neuronal and mitochondrial dysfunction, so many readouts change secondarily. That does not show Parkin performs a step of this process. |
| GO:0044314 protein K27-linked ubiquitination | IDA PMID:17097639 Parkin is an E3 ubiquitin-ligase for normal and mutant ataxi... | ACCEPT | Summary: Parkin assembles Lys27-linked chains (e.g. on VDAC1 during mitophagy). Reason: Experimentally supported linkage type. Supporting Evidence: PMID:20098416 Subsequently, Parkin mediates the formation of two distinct poly-ubiquitin chains, linked through Lys 63 and Lys 27. PMID:20098416 Strikingly, we identified VDAC1 (voltage-dependent anion channel 1) as a target for Parkin-mediated Lys 27 poly-ubiquitylation and mitophagy. |
| GO:0044314 protein K27-linked ubiquitination | TAS PMID:20098416 PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p6... | ACCEPT | Summary: Parkin assembles Lys27-linked chains (e.g. on VDAC1 during mitophagy). Reason: Experimentally supported linkage type. Supporting Evidence: PMID:20098416 Subsequently, Parkin mediates the formation of two distinct poly-ubiquitin chains, linked through Lys 63 and Lys 27. PMID:20098416 Strikingly, we identified VDAC1 (voltage-dependent anion channel 1) as a target for Parkin-mediated Lys 27 poly-ubiquitylation and mitophagy. |
| GO:0044314 protein K27-linked ubiquitination | TAS PMID:23626584 Structure and Function of Parkin, PINK1, and DJ-1, the Three... | ACCEPT | Summary: Parkin assembles Lys27-linked chains (e.g. on VDAC1 during mitophagy). Reason: Experimentally supported linkage type. Supporting Evidence: PMID:20098416 Subsequently, Parkin mediates the formation of two distinct poly-ubiquitin chains, linked through Lys 63 and Lys 27. PMID:20098416 Strikingly, we identified VDAC1 (voltage-dependent anion channel 1) as a target for Parkin-mediated Lys 27 poly-ubiquitylation and mitophagy. |
| GO:0044828 host-mediated suppression of viral genome replication | IDA PMID:25244949 Hepatitis C virus core protein suppresses mitophagy by inter... | UNDECIDED | Summary: HCV core protein binds Parkin and suppresses Parkin-mediated mitophagy. Silencing Parkin reduced HCV core expression, implying that Parkin supports rather than suppresses viral propagation. Reason: The abstract seems to contradict a host-suppression role, but only the abstract is available. I cannot see the data behind the IDA and so do not overrule it. Supporting Evidence: PMID:25244949 Silencing Parkin suppressed HCV core protein expression, suggesting a functional role for the interaction between the HCV core protein and Parkin in HCV propagation. |
| GO:0044877 protein-containing complex binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Parkin binds the LUBAC complex. Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:23453807 Under cellular stress, parkin is recruited to the linear ubiquitin assembly complex and increases linear ubiquitination of NF-ΞΊB essential modulator (NEMO), which is essential for canonical NF-ΞΊB signaling. |
| GO:0044877 protein-containing complex binding | IPI PMID:23453807 The E3 ligase parkin maintains mitochondrial integrity by in... | KEEP AS NON CORE | Summary: Parkin binds the LUBAC complex. Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:23453807 Under cellular stress, parkin is recruited to the linear ubiquitin assembly complex and increases linear ubiquitination of NF-ΞΊB essential modulator (NEMO), which is essential for canonical NF-ΞΊB signaling. |
| GO:0045202 synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred synapse location. Reason: Neuronal or synaptic location, consistent with Parkin being a cytosolic protein abundant in neurons. Not informative about its core function. |
| GO:0045732 positive regulation of protein catabolic process | TAS PMID:22988876 The importance of Wnt signalling for neurodegeneration in Pa... | KEEP AS NON CORE | Summary: Parkin promotes beta-catenin degradation (review). Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:19591802 We now show that Parkin, an E3 ubiquitin ligase linked to familial PD, regulates beta-catenin protein levels in vivo. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:23453807 The E3 ligase parkin maintains mitochondrial integrity by in... | MARK AS OVER ANNOTATED | Summary: Parkin-dependent NF-kappaB activation leads to OPA1 transcription. Reason: Transcriptional induction is several steps downstream of Parkin and is mediated by NF-kappaB, not Parkin. Supporting Evidence: PMID:23453807 As a result, the mitochondrial guanosine triphosphatase OPA1 is transcriptionally upregulated via NF-ΞΊB-responsive promoter elements for maintenance of mitochondrial integrity and protection from stress-induced cell death. |
| GO:0046329 negative regulation of JNK cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Parkin suppresses JNK activation in some neuronal models (ortholog transfer). Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. |
| GO:0046676 negative regulation of insulin secretion | IDA PMID:24187134 Identification of the ubiquitin-like domain of midnolin as a... | MARK AS OVER ANNOTATED | Summary: Parkin overexpression diminished insulin secretion in MIN6 cells. Reason: Overexpression effect in a study centred on midnolin; no evidence of a physiological role in insulin secretion. Supporting Evidence: PMID:24187134 Overexpression of parkin, an ubiquitin E3 ligase exhibiting an ubiquitin-like domain with high homology to the identified, diminished insulin secretion in MIN6 cells but had only some effect on glucokinase activity. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:17097639 Parkin is an E3 ubiquitin-ligase for normal and mutant ataxi... | KEEP AS NON CORE | Summary: Parkin and Parkin-ubiquitinated mitochondria cluster perinuclearly. Reason: Non-core location. Supporting Evidence: PMID:20890124 These results demonstrate that mitochondria are aggregated by p62, following its recruitment by Parkin in a VDAC1-independent manner. |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Parkin and Parkin-ubiquitinated mitochondria cluster perinuclearly. Reason: Non-core location. Supporting Evidence: PMID:20890124 These results demonstrate that mitochondria are aggregated by p62, following its recruitment by Parkin in a VDAC1-independent manner. |
| GO:0050804 modulation of chemical synaptic transmission | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Parkin affects synaptic transmission (e.g. dopamine release, glutamatergic transmission in knockouts). Reason: Supported by IBA and phenotypes, but indirect relative to the core E3 function. |
| GO:0050804 modulation of chemical synaptic transmission | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Parkin affects synaptic transmission (e.g. dopamine release, glutamatergic transmission in knockouts). Reason: Supported by IBA and phenotypes, but indirect relative to the core E3 function. |
| GO:0050821 protein stabilization | IMP PMID:19229105 Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex p... | KEEP AS NON CORE | Summary: Parkin monoubiquitination can stabilize substrates (e.g. increases Bcl-2 levels). Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:20889974 Parkin directly binds to Bcl-2 via its C terminus and mediates the mono-ubiquitination of Bcl-2, which increases the steady-state levels of Bcl-2. |
| GO:0051087 protein-folding chaperone binding | IPI PMID:15603737 BAG5 inhibits parkin and enhances dopaminergic neuron degene... | KEEP AS NON CORE | Summary: Parkin co-purifies with chaperones (Hsp70, HSPA9, BAG5 and others). Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:19725078 This study provides further evidence for a role for Parkin in regulating mitochondrial activity within cells. |
| GO:0051087 protein-folding chaperone binding | IPI PMID:19725078 Proteomic analysis of increased Parkin expression and its in... | KEEP AS NON CORE | Summary: Parkin co-purifies with chaperones (Hsp70, HSPA9, BAG5 and others). Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:19725078 This study provides further evidence for a role for Parkin in regulating mitochondrial activity within cells. |
| GO:0051087 protein-folding chaperone binding | IPI PMID:19725078 Proteomic analysis of increased Parkin expression and its in... | KEEP AS NON CORE | Summary: Parkin co-purifies with chaperones (Hsp70, HSPA9, BAG5 and others). Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:19725078 This study provides further evidence for a role for Parkin in regulating mitochondrial activity within cells. |
| GO:0051087 protein-folding chaperone binding | IPI PMID:21753002 Parkin interacts with Ambra1 to induce mitophagy. | KEEP AS NON CORE | Summary: Parkin co-purifies with chaperones (Hsp70, HSPA9, BAG5 and others). Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:19725078 This study provides further evidence for a role for Parkin in regulating mitochondrial activity within cells. |
| GO:0051087 protein-folding chaperone binding | IPI PMID:21753002 Parkin interacts with Ambra1 to induce mitophagy. | KEEP AS NON CORE | Summary: Parkin co-purifies with chaperones (Hsp70, HSPA9, BAG5 and others). Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:19725078 This study provides further evidence for a role for Parkin in regulating mitochondrial activity within cells. |
| GO:0051087 protein-folding chaperone binding | IPI PMID:21753002 Parkin interacts with Ambra1 to induce mitophagy. | KEEP AS NON CORE | Summary: Parkin co-purifies with chaperones (Hsp70, HSPA9, BAG5 and others). Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:19725078 This study provides further evidence for a role for Parkin in regulating mitochondrial activity within cells. |
| GO:0051412 response to corticosterone | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred response to corticosterone. Reason: Ortholog-transferred (Ensembl Compara) annotation, most likely from a rodent phenotype or expression study. Parkin loss causes broad neuronal and mitochondrial dysfunction, so many readouts change secondarily. That does not show Parkin performs a step of this process. |
| GO:0051582 positive regulation of neurotransmitter uptake | IMP PMID:22314364 Parkin controls dopamine utilization in human midbrain dopam... | KEEP AS NON CORE | Summary: Loss of Parkin in human DA neurons reduces dopamine uptake. Reason: Experimental but indirect and non-core. Supporting Evidence: PMID:22314364 We demonstrate that loss of parkin in human midbrain DA neurons greatly increases the transcription of monoamine oxidases and oxidative stress, significantly reduces DA uptake and increases spontaneous DA release. |
| GO:0051646 mitochondrion localization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Parkin-dependent degradation of Miro arrests mitochondrial movement. Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:22078885 The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner. |
| GO:0051865 protein autoubiquitination | IDA PMID:12628165 Parkin is a component of an SCF-like ubiquitin ligase comple... | ACCEPT | Summary: Parkin autoubiquitinates; this is restrained by its Ubl domain and is a standard readout of its activation. Reason: Directly shown. Supporting Evidence: PMID:21694720 We now demonstrate that the ubiquitin-like domain of Parkin functions to inhibit its autoubiquitination. PMID:16955485 Moreover, the physical association of SUMO-1 with parkin results in an increase in the nuclear transport of parkin as well as its self-ubiquitination. |
| GO:0051865 protein autoubiquitination | IDA PMID:15728840 Parkin mediates nonclassical, proteasomal-independent ubiqui... | ACCEPT | Summary: Parkin autoubiquitinates; this is restrained by its Ubl domain and is a standard readout of its activation. Reason: Directly shown. Supporting Evidence: PMID:21694720 We now demonstrate that the ubiquitin-like domain of Parkin functions to inhibit its autoubiquitination. PMID:16955485 Moreover, the physical association of SUMO-1 with parkin results in an increase in the nuclear transport of parkin as well as its self-ubiquitination. |
| GO:0051865 protein autoubiquitination | IDA PMID:16352719 Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, ... | ACCEPT | Summary: Parkin autoubiquitinates; this is restrained by its Ubl domain and is a standard readout of its activation. Reason: Directly shown. Supporting Evidence: PMID:21694720 We now demonstrate that the ubiquitin-like domain of Parkin functions to inhibit its autoubiquitination. PMID:16955485 Moreover, the physical association of SUMO-1 with parkin results in an increase in the nuclear transport of parkin as well as its self-ubiquitination. |
| GO:0051865 protein autoubiquitination | IDA PMID:17512523 Parkin interacts with LIM Kinase 1 and reduces its cofilin-p... | ACCEPT | Summary: Parkin autoubiquitinates; this is restrained by its Ubl domain and is a standard readout of its activation. Reason: Directly shown. Supporting Evidence: PMID:21694720 We now demonstrate that the ubiquitin-like domain of Parkin functions to inhibit its autoubiquitination. PMID:16955485 Moreover, the physical association of SUMO-1 with parkin results in an increase in the nuclear transport of parkin as well as its self-ubiquitination. |
| GO:0051881 regulation of mitochondrial membrane potential | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred regulation of mitochondrial membrane potential. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. |
| GO:0051967 negative regulation of synaptic transmission, glutamatergic | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred negative regulation of glutamatergic transmission. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. |
| GO:0060544 regulation of necroptotic process | TAS Reactome:R-HSA-5675482 | KEEP AS NON CORE | Summary: Parkin polyubiquitinates RIPK3 and prevents RIPK1-RIPK3 necrosome formation. Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:31358971 Parkin prevents the formation of the RIPK1-RIPK3 complex by promoting polyubiquitination of RIPK3. |
| GO:0060828 regulation of canonical Wnt signaling pathway | TAS PMID:24115276 The regulation and deregulation of Wnt signaling by PARK gen... | KEEP AS NON CORE | Summary: Parkin regulates beta-catenin levels and Wnt signalling. Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:19591802 These findings demonstrate a novel regulation of Wnt signaling by Parkin and suggest that Parkin protects DA neurons against excessive Wnt signaling and beta-catenin-induced cell death. |
| GO:0061630 ubiquitin protein ligase activity | EXP PMID:23770887 Structure and function of Parkin E3 ubiquitin ligase reveals... | ACCEPT | Summary: Parkin is an RBR (RING-between-RING) E3 ubiquitin ligase. It binds E2~Ub via RING1 and transfers ubiquitin through a thioester on catalytic Cys431 in RING2. It is activated by PINK1 phosphorylation of its Ubl and of ubiquitin at Ser65. Reason: Core molecular function. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. PMID:24751536 Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. |
| GO:0061630 ubiquitin protein ligase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Parkin is an RBR (RING-between-RING) E3 ubiquitin ligase. It binds E2~Ub via RING1 and transfers ubiquitin through a thioester on catalytic Cys431 in RING2. It is activated by PINK1 phosphorylation of its Ubl and of ubiquitin at Ser65. Reason: Core molecular function. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. PMID:24751536 Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:10973942 Parkin suppresses unfolded protein stress-induced cell death... | ACCEPT | Summary: Parkin is an RBR (RING-between-RING) E3 ubiquitin ligase. It binds E2~Ub via RING1 and transfers ubiquitin through a thioester on catalytic Cys431 in RING2. It is activated by PINK1 phosphorylation of its Ubl and of ubiquitin at Ser65. Reason: Core molecular function. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. PMID:24751536 Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:11439185 An unfolded putative transmembrane polypeptide, which can le... | ACCEPT | Summary: Parkin is an RBR (RING-between-RING) E3 ubiquitin ligase. It binds E2~Ub via RING1 and transfers ubiquitin through a thioester on catalytic Cys431 in RING2. It is activated by PINK1 phosphorylation of its Ubl and of ubiquitin at Ser65. Reason: Core molecular function. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. PMID:24751536 Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:12150907 CHIP is associated with Parkin, a gene responsible for famil... | ACCEPT | Summary: Parkin is an RBR (RING-between-RING) E3 ubiquitin ligase. It binds E2~Ub via RING1 and transfers ubiquitin through a thioester on catalytic Cys431 in RING2. It is activated by PINK1 phosphorylation of its Ubl and of ubiquitin at Ser65. Reason: Core molecular function. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. PMID:24751536 Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:12628165 Parkin is a component of an SCF-like ubiquitin ligase comple... | ACCEPT | Summary: Parkin is an RBR (RING-between-RING) E3 ubiquitin ligase. It binds E2~Ub via RING1 and transfers ubiquitin through a thioester on catalytic Cys431 in RING2. It is activated by PINK1 phosphorylation of its Ubl and of ubiquitin at Ser65. Reason: Core molecular function. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. PMID:24751536 Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:12925569 The autosomal recessive juvenile Parkinson disease gene prod... | ACCEPT | Summary: Parkin is an RBR (RING-between-RING) E3 ubiquitin ligase. It binds E2~Ub via RING1 and transfers ubiquitin through a thioester on catalytic Cys431 in RING2. It is activated by PINK1 phosphorylation of its Ubl and of ubiquitin at Ser65. Reason: Core molecular function. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. PMID:24751536 Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:16227987 Dopamine covalently modifies and functionally inactivates pa... | ACCEPT | Summary: Parkin is an RBR (RING-between-RING) E3 ubiquitin ligase. It binds E2~Ub via RING1 and transfers ubiquitin through a thioester on catalytic Cys431 in RING2. It is activated by PINK1 phosphorylation of its Ubl and of ubiquitin at Ser65. Reason: Core molecular function. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. PMID:24751536 Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:19229105 Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex p... | ACCEPT | Summary: Parkin is an RBR (RING-between-RING) E3 ubiquitin ligase. It binds E2~Ub via RING1 and transfers ubiquitin through a thioester on catalytic Cys431 in RING2. It is activated by PINK1 phosphorylation of its Ubl and of ubiquitin at Ser65. Reason: Core molecular function. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. PMID:24751536 Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:19880420 Phosphorylation of parkin by Parkinson disease-linked kinase... | ACCEPT | Summary: Parkin is an RBR (RING-between-RING) E3 ubiquitin ligase. It binds E2~Ub via RING1 and transfers ubiquitin through a thioester on catalytic Cys431 in RING2. It is activated by PINK1 phosphorylation of its Ubl and of ubiquitin at Ser65. Reason: Core molecular function. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. PMID:24751536 Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:20823226 Phosphorylation by the c-Abl protein tyrosine kinase inhibit... | ACCEPT | Summary: Parkin is an RBR (RING-between-RING) E3 ubiquitin ligase. It binds E2~Ub via RING1 and transfers ubiquitin through a thioester on catalytic Cys431 in RING2. It is activated by PINK1 phosphorylation of its Ubl and of ubiquitin at Ser65. Reason: Core molecular function. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. PMID:24751536 Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:21376232 PARIS (ZNF746) repression of PGC-1Ξ± contributes to neurodege... | ACCEPT | Summary: Parkin is an RBR (RING-between-RING) E3 ubiquitin ligase. It binds E2~Ub via RING1 and transfers ubiquitin through a thioester on catalytic Cys431 in RING2. It is activated by PINK1 phosphorylation of its Ubl and of ubiquitin at Ser65. Reason: Core molecular function. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. PMID:24751536 Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:23685073 Mutations in the intellectual disability gene Ube2a cause ne... | ACCEPT | Summary: Parkin is an RBR (RING-between-RING) E3 ubiquitin ligase. It binds E2~Ub via RING1 and transfers ubiquitin through a thioester on catalytic Cys431 in RING2. It is activated by PINK1 phosphorylation of its Ubl and of ubiquitin at Ser65. Reason: Core molecular function. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. PMID:24751536 Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:23858059 Parkin-dependent degradation of the F-box protein Fbw7Ξ² prom... | ACCEPT | Summary: Parkin is an RBR (RING-between-RING) E3 ubiquitin ligase. It binds E2~Ub via RING1 and transfers ubiquitin through a thioester on catalytic Cys431 in RING2. It is activated by PINK1 phosphorylation of its Ubl and of ubiquitin at Ser65. Reason: Core molecular function. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. PMID:24751536 Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:25621951 USP30 and parkin homeostatically regulate atypical ubiquitin... | ACCEPT | Summary: Parkin is an RBR (RING-between-RING) E3 ubiquitin ligase. It binds E2~Ub via RING1 and transfers ubiquitin through a thioester on catalytic Cys431 in RING2. It is activated by PINK1 phosphorylation of its Ubl and of ubiquitin at Ser65. Reason: Core molecular function. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. PMID:24751536 Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. |
| GO:0061630 ubiquitin protein ligase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Parkin is an RBR (RING-between-RING) E3 ubiquitin ligase. It binds E2~Ub via RING1 and transfers ubiquitin through a thioester on catalytic Cys431 in RING2. It is activated by PINK1 phosphorylation of its Ubl and of ubiquitin at Ser65. Reason: Core molecular function. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. PMID:24751536 Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. |
| GO:0061630 ubiquitin protein ligase activity | IMP PMID:32047033 Decision between mitophagy and apoptosis by Parkin via VDAC1... | ACCEPT | Summary: Parkin is an RBR (RING-between-RING) E3 ubiquitin ligase. It binds E2~Ub via RING1 and transfers ubiquitin through a thioester on catalytic Cys431 in RING2. It is activated by PINK1 phosphorylation of its Ubl and of ubiquitin at Ser65. Reason: Core molecular function. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. PMID:24751536 Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. |
| GO:0061630 ubiquitin protein ligase activity | NAS PMID:10973942 Parkin suppresses unfolded protein stress-induced cell death... | ACCEPT | Summary: Parkin is an RBR (RING-between-RING) E3 ubiquitin ligase. It binds E2~Ub via RING1 and transfers ubiquitin through a thioester on catalytic Cys431 in RING2. It is activated by PINK1 phosphorylation of its Ubl and of ubiquitin at Ser65. Reason: Core molecular function. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. PMID:24751536 Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. |
| GO:0061630 ubiquitin protein ligase activity | NAS PMID:18221368 Biochemical aspects of the neuroprotective mechanism of PTEN... | ACCEPT | Summary: Parkin is an RBR (RING-between-RING) E3 ubiquitin ligase. It binds E2~Ub via RING1 and transfers ubiquitin through a thioester on catalytic Cys431 in RING2. It is activated by PINK1 phosphorylation of its Ubl and of ubiquitin at Ser65. Reason: Core molecular function. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. PMID:24751536 Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. |
| GO:0061630 ubiquitin protein ligase activity | TAS Reactome:R-HSA-5689111 | ACCEPT | Summary: Parkin is an RBR (RING-between-RING) E3 ubiquitin ligase. It binds E2~Ub via RING1 and transfers ubiquitin through a thioester on catalytic Cys431 in RING2. It is activated by PINK1 phosphorylation of its Ubl and of ubiquitin at Ser65. Reason: Core molecular function. Supporting Evidence: PMID:10973942 Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. PMID:23770887 In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin's cellular active site. PMID:23754282 Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. PMID:24751536 Recombinant TcPINK1 directly phosphorylated ubiquitin and phospho-ubiquitin activated Parkin E3 ubiquitin ligase activity in cell-free assays. |
| GO:0061734 type 2 mitophagy | IDA PMID:19029340 Parkin is recruited selectively to impaired mitochondria and... | ACCEPT | Summary: Parkin is selectively recruited to depolarized mitochondria and promotes their elimination (depolarization-induced, type 2 mitophagy). Reason: Core process. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. PMID:19029340 After recruitment, Parkin mediates the engulfment of mitochondria by autophagosomes and the selective elimination of impaired mitochondria. |
| GO:0070050 neuron cellular homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Parkin maintains neuronal homeostasis (ortholog transfer). Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. |
| GO:0070534 protein K63-linked ubiquitination | IDA PMID:15728840 Parkin mediates nonclassical, proteasomal-independent ubiqui... | ACCEPT | Summary: Parkin forms K63-linked chains (on mitochondria, NEMO/TRAF2, synphilin-1). Reason: Directly shown in several studies. Supporting Evidence: PMID:15728840 In addition we found that parkin-mediated ubiquitination of proteins within Lewy-body-like inclusions formed by the coexpression of synphilin-1, alpha-synuclein, and parkin occurs predominantly via K63 linkages and that the formation of these inclusions is enhanced by K63-linked ubiquitination. PMID:25621951 We find that mitochondrial damage stimulates parkin to assemble Lys 6, Lys 11 and Lys 63 chains on mitochondria, and that USP30 is a ubiquitin-specific deubiquitylase with a strong preference for cleaving Lys 6- and Lys 11-linked multimers. PMID:17314283 Finally, we present evidence that parkin interacts with and promotes degradation-independent ubiquitylation of IKKgamma/NEMO (NF-kappaB essential modifier) and TRAF2 [TNF (tumor necrosis factor) receptor-associated factor 2], two critical components of the NF-kappaB pathway. |
| GO:0070534 protein K63-linked ubiquitination | IDA PMID:17314283 Parkin mediates neuroprotection through activation of Ikappa... | ACCEPT | Summary: Parkin forms K63-linked chains (on mitochondria, NEMO/TRAF2, synphilin-1). Reason: Directly shown in several studies. Supporting Evidence: PMID:15728840 In addition we found that parkin-mediated ubiquitination of proteins within Lewy-body-like inclusions formed by the coexpression of synphilin-1, alpha-synuclein, and parkin occurs predominantly via K63 linkages and that the formation of these inclusions is enhanced by K63-linked ubiquitination. PMID:25621951 We find that mitochondrial damage stimulates parkin to assemble Lys 6, Lys 11 and Lys 63 chains on mitochondria, and that USP30 is a ubiquitin-specific deubiquitylase with a strong preference for cleaving Lys 6- and Lys 11-linked multimers. PMID:17314283 Finally, we present evidence that parkin interacts with and promotes degradation-independent ubiquitylation of IKKgamma/NEMO (NF-kappaB essential modifier) and TRAF2 [TNF (tumor necrosis factor) receptor-associated factor 2], two critical components of the NF-kappaB pathway. |
| GO:0070534 protein K63-linked ubiquitination | IDA PMID:19880420 Phosphorylation of parkin by Parkinson disease-linked kinase... | ACCEPT | Summary: Parkin forms K63-linked chains (on mitochondria, NEMO/TRAF2, synphilin-1). Reason: Directly shown in several studies. Supporting Evidence: PMID:15728840 In addition we found that parkin-mediated ubiquitination of proteins within Lewy-body-like inclusions formed by the coexpression of synphilin-1, alpha-synuclein, and parkin occurs predominantly via K63 linkages and that the formation of these inclusions is enhanced by K63-linked ubiquitination. PMID:25621951 We find that mitochondrial damage stimulates parkin to assemble Lys 6, Lys 11 and Lys 63 chains on mitochondria, and that USP30 is a ubiquitin-specific deubiquitylase with a strong preference for cleaving Lys 6- and Lys 11-linked multimers. PMID:17314283 Finally, we present evidence that parkin interacts with and promotes degradation-independent ubiquitylation of IKKgamma/NEMO (NF-kappaB essential modifier) and TRAF2 [TNF (tumor necrosis factor) receptor-associated factor 2], two critical components of the NF-kappaB pathway. |
| GO:0070534 protein K63-linked ubiquitination | IDA PMID:25621951 USP30 and parkin homeostatically regulate atypical ubiquitin... | ACCEPT | Summary: Parkin forms K63-linked chains (on mitochondria, NEMO/TRAF2, synphilin-1). Reason: Directly shown in several studies. Supporting Evidence: PMID:15728840 In addition we found that parkin-mediated ubiquitination of proteins within Lewy-body-like inclusions formed by the coexpression of synphilin-1, alpha-synuclein, and parkin occurs predominantly via K63 linkages and that the formation of these inclusions is enhanced by K63-linked ubiquitination. PMID:25621951 We find that mitochondrial damage stimulates parkin to assemble Lys 6, Lys 11 and Lys 63 chains on mitochondria, and that USP30 is a ubiquitin-specific deubiquitylase with a strong preference for cleaving Lys 6- and Lys 11-linked multimers. PMID:17314283 Finally, we present evidence that parkin interacts with and promotes degradation-independent ubiquitylation of IKKgamma/NEMO (NF-kappaB essential modifier) and TRAF2 [TNF (tumor necrosis factor) receptor-associated factor 2], two critical components of the NF-kappaB pathway. |
| GO:0070534 protein K63-linked ubiquitination | NAS PMID:20890124 p62/SQSTM1 is required for Parkin-induced mitochondrial clus... | ACCEPT | Summary: Parkin forms K63-linked chains (on mitochondria, NEMO/TRAF2, synphilin-1). Reason: Directly shown in several studies. Supporting Evidence: PMID:15728840 In addition we found that parkin-mediated ubiquitination of proteins within Lewy-body-like inclusions formed by the coexpression of synphilin-1, alpha-synuclein, and parkin occurs predominantly via K63 linkages and that the formation of these inclusions is enhanced by K63-linked ubiquitination. PMID:25621951 We find that mitochondrial damage stimulates parkin to assemble Lys 6, Lys 11 and Lys 63 chains on mitochondria, and that USP30 is a ubiquitin-specific deubiquitylase with a strong preference for cleaving Lys 6- and Lys 11-linked multimers. PMID:17314283 Finally, we present evidence that parkin interacts with and promotes degradation-independent ubiquitylation of IKKgamma/NEMO (NF-kappaB essential modifier) and TRAF2 [TNF (tumor necrosis factor) receptor-associated factor 2], two critical components of the NF-kappaB pathway. |
| GO:0070534 protein K63-linked ubiquitination | TAS PMID:18221368 Biochemical aspects of the neuroprotective mechanism of PTEN... | ACCEPT | Summary: Parkin forms K63-linked chains (on mitochondria, NEMO/TRAF2, synphilin-1). Reason: Directly shown in several studies. Supporting Evidence: PMID:15728840 In addition we found that parkin-mediated ubiquitination of proteins within Lewy-body-like inclusions formed by the coexpression of synphilin-1, alpha-synuclein, and parkin occurs predominantly via K63 linkages and that the formation of these inclusions is enhanced by K63-linked ubiquitination. PMID:25621951 We find that mitochondrial damage stimulates parkin to assemble Lys 6, Lys 11 and Lys 63 chains on mitochondria, and that USP30 is a ubiquitin-specific deubiquitylase with a strong preference for cleaving Lys 6- and Lys 11-linked multimers. PMID:17314283 Finally, we present evidence that parkin interacts with and promotes degradation-independent ubiquitylation of IKKgamma/NEMO (NF-kappaB essential modifier) and TRAF2 [TNF (tumor necrosis factor) receptor-associated factor 2], two critical components of the NF-kappaB pathway. |
| GO:0070585 protein localization to mitochondrion | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Parkin is relocalized to mitochondria by PINK1. Reason: Parkin is the protein being localized; it does not drive the localization of other proteins. Non-core. Supporting Evidence: PMID:18957282 In detail, Parkin phosphorylation by PINK1 on its linker region promotes its mitochondrial translocation, and the RING1 domain of Parkin is critical for this occurrence. |
| GO:0070842 aggresome assembly | IMP PMID:14645198 Parkin is recruited into aggresomes in a stress-specific man... | KEEP AS NON CORE | Summary: Parkin influences aggresome formation in neuronal cells, and K63 ubiquitination by Parkin promotes inclusion formation. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:14645198 Our findings suggest that parkin is important for aggresome formation in human neuronal cells and may lead to a better understanding of the biogenesis of LBs in sporadic PD. PMID:15728840 In addition we found that parkin-mediated ubiquitination of proteins within Lewy-body-like inclusions formed by the coexpression of synphilin-1, alpha-synuclein, and parkin occurs predominantly via K63 linkages and that the formation of these inclusions is enhanced by K63-linked ubiquitination. |
| GO:0070936 protein K48-linked ubiquitination | IDA PMID:21376232 PARIS (ZNF746) repression of PGC-1Ξ± contributes to neurodege... | ACCEPT | Summary: Parkin forms K48-linked chains on substrates (e.g. PARIS, Fbw7beta) for proteasomal degradation. Reason: Consistent with Parkin-mediated proteasomal degradation. Supporting Evidence: PMID:23858059 Specifically, parkin targets the SCF substrate adapter Fbw7Ξ² for proteasomal degradation. |
| GO:0070936 protein K48-linked ubiquitination | IDA PMID:23858059 Parkin-dependent degradation of the F-box protein Fbw7Ξ² prom... | ACCEPT | Summary: Parkin forms K48-linked chains on substrates (e.g. PARIS, Fbw7beta) for proteasomal degradation. Reason: Consistent with Parkin-mediated proteasomal degradation. Supporting Evidence: PMID:23858059 Specifically, parkin targets the SCF substrate adapter Fbw7Ξ² for proteasomal degradation. |
| GO:0070979 protein K11-linked ubiquitination | IDA PMID:25621951 USP30 and parkin homeostatically regulate atypical ubiquitin... | ACCEPT | Summary: On damaged mitochondria Parkin assembles Lys6, Lys11 and Lys63 chains. Reason: Directly shown by linkage-specific mass spectrometry. Supporting Evidence: PMID:25621951 We find that mitochondrial damage stimulates parkin to assemble Lys 6, Lys 11 and Lys 63 chains on mitochondria, and that USP30 is a ubiquitin-specific deubiquitylase with a strong preference for cleaving Lys 6- and Lys 11-linked multimers. |
| GO:0071287 cellular response to manganese ion | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Response to manganese; the TAS source is a study of LRRK2 knockdown and Mn toxicity. Reason: The cited study concerns LRRK2, and there is no evidence for a manganese-specific Parkin function. |
| GO:0071287 cellular response to manganese ion | TAS PMID:23628791 Down-regulation of LRRK2 in control and DAT transfected HEK ... | MARK AS OVER ANNOTATED | Summary: Response to manganese; the TAS source is a study of LRRK2 knockdown and Mn toxicity. Reason: The cited study concerns LRRK2, and there is no evidence for a manganese-specific Parkin function. |
| GO:0085020 protein K6-linked ubiquitination | IDA PMID:25621951 USP30 and parkin homeostatically regulate atypical ubiquitin... | ACCEPT | Summary: Parkin assembles Lys6-linked chains on damaged mitochondria. Reason: Directly shown. Supporting Evidence: PMID:25621951 We find that mitochondrial damage stimulates parkin to assemble Lys 6, Lys 11 and Lys 63 chains on mitochondria, and that USP30 is a ubiquitin-specific deubiquitylase with a strong preference for cleaving Lys 6- and Lys 11-linked multimers. |
| GO:0085020 protein K6-linked ubiquitination | TAS PMID:23626584 Structure and Function of Parkin, PINK1, and DJ-1, the Three... | ACCEPT | Summary: Parkin assembles Lys6-linked chains on damaged mitochondria. Reason: Directly shown. Supporting Evidence: PMID:25621951 We find that mitochondrial damage stimulates parkin to assemble Lys 6, Lys 11 and Lys 63 chains on mitochondria, and that USP30 is a ubiquitin-specific deubiquitylase with a strong preference for cleaving Lys 6- and Lys 11-linked multimers. |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IDA PMID:19591802 Parkin protects dopaminergic neurons from excessive Wnt/beta... | KEEP AS NON CORE | Summary: Parkin regulates beta-catenin levels and protects DA neurons against excessive Wnt signalling. Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:19591802 We now show that Parkin, an E3 ubiquitin ligase linked to familial PD, regulates beta-catenin protein levels in vivo. PMID:19591802 These findings demonstrate a novel regulation of Wnt signaling by Parkin and suggest that Parkin protects DA neurons against excessive Wnt signaling and beta-catenin-induced cell death. |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | TAS PMID:22988876 The importance of Wnt signalling for neurodegeneration in Pa... | KEEP AS NON CORE | Summary: Parkin regulates beta-catenin levels and protects DA neurons against excessive Wnt signalling. Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:19591802 We now show that Parkin, an E3 ubiquitin ligase linked to familial PD, regulates beta-catenin protein levels in vivo. PMID:19591802 These findings demonstrate a novel regulation of Wnt signaling by Parkin and suggest that Parkin protects DA neurons against excessive Wnt signaling and beta-catenin-induced cell death. |
| GO:0090141 positive regulation of mitochondrial fission | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Parkin promotes mitochondrial fragmentation via mitofusin degradation (ortholog transfer). Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:20871098 The ubiquitination of several mitochondrial proteins, including mitofusin 1 and mitofusin 2, were detected within 3 h of CCCP treatment. |
| GO:0090201 negative regulation of release of cytochrome c from mitochondria | IDA PMID:19880420 Phosphorylation of parkin by Parkinson disease-linked kinase... | KEEP AS NON CORE | Summary: Parkin limits cytochrome c release and stress-induced apoptosis (e.g. via OPA1 upregulation). Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:23453807 As a result, the mitochondrial guanosine triphosphatase OPA1 is transcriptionally upregulated via NF-ΞΊB-responsive promoter elements for maintenance of mitochondrial integrity and protection from stress-induced cell death. |
| GO:0090201 negative regulation of release of cytochrome c from mitochondria | IDA PMID:23453807 The E3 ligase parkin maintains mitochondrial integrity by in... | KEEP AS NON CORE | Summary: Parkin limits cytochrome c release and stress-induced apoptosis (e.g. via OPA1 upregulation). Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:23453807 As a result, the mitochondrial guanosine triphosphatase OPA1 is transcriptionally upregulated via NF-ΞΊB-responsive promoter elements for maintenance of mitochondrial integrity and protection from stress-induced cell death. |
| GO:0090258 negative regulation of mitochondrial fission | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred negative regulation of mitochondrial fission. Reason: The direction conflicts with Parkin-mediated mitofusin degradation, which favours fragmentation. Probably a context-specific rodent phenotype. |
| GO:0090394 negative regulation of excitatory postsynaptic potential | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred negative regulation of excitatory postsynaptic potential. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. |
| GO:0097237 cellular response to toxic substance | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Parkin overexpression protects neurons from kainate excitotoxicity through cyclin E regulation. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:12628165 Furthermore, parkin overexpression attenuates the accumulation of cyclin E in toxin-treated primary neurons, including midbrain dopamine neurons, and protects them from apoptosis. |
| GO:0097237 cellular response to toxic substance | IMP PMID:12628165 Parkin is a component of an SCF-like ubiquitin ligase comple... | KEEP AS NON CORE | Summary: Parkin overexpression protects neurons from kainate excitotoxicity through cyclin E regulation. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:12628165 Furthermore, parkin overexpression attenuates the accumulation of cyclin E in toxin-treated primary neurons, including midbrain dopamine neurons, and protects them from apoptosis. |
| GO:0097413 Lewy body | TAS PMID:24522549 Oxidative stress-induced signaling pathways implicated in th... | KEEP AS NON CORE | Summary: Parkin is found in Lewy bodies. Reason: Pathological inclusion location; non-core. Supporting Evidence: PMID:15728840 In addition we found that parkin-mediated ubiquitination of proteins within Lewy-body-like inclusions formed by the coexpression of synphilin-1, alpha-synuclein, and parkin occurs predominantly via K63 linkages and that the formation of these inclusions is enhanced by K63-linked ubiquitination. |
| GO:0097602 cullin family protein binding | IDA PMID:12628165 Parkin is a component of an SCF-like ubiquitin ligase comple... | KEEP AS NON CORE | Summary: Parkin associates with Cullin-1 in an FBXW7-containing complex. Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:12628165 Here we show that parkin functions in a multiprotein ubiquitin ligase complex that includes the F-box/WD repeat protein hSel-10 and Cullin-1. |
| GO:0097708 intracellular vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred intracellular vesicle location. Reason: Neuronal or synaptic location, consistent with Parkin being a cytosolic protein abundant in neurons. Not informative about its core function. |
| GO:0098588 bounding membrane of organelle | IEA GO_REF:0000117 | ACCEPT | Summary: Broad electronic location covering the mitochondrial outer membrane. Reason: Correct but broad. Supporting Evidence: PMID:19029340 Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. |
| GO:0098691 dopaminergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred dopaminergic synapse location. Reason: Neuronal or synaptic location, consistent with Parkin being a cytosolic protein abundant in neurons. Not informative about its core function. |
| GO:0098793 presynapse | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Parkin reported in presynaptic terminals. Reason: Neuronal or synaptic location, consistent with Parkin being a cytosolic protein abundant in neurons. Not informative about its core function. |
| GO:0098793 presynapse | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Parkin reported in presynaptic terminals. Reason: Neuronal or synaptic location, consistent with Parkin being a cytosolic protein abundant in neurons. Not informative about its core function. |
| GO:0098794 postsynapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred postsynapse location. Reason: Neuronal or synaptic location, consistent with Parkin being a cytosolic protein abundant in neurons. Not informative about its core function. |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred glutamatergic synapse location. Reason: Neuronal or synaptic location, consistent with Parkin being a cytosolic protein abundant in neurons. Not informative about its core function. |
| GO:0099072 regulation of postsynaptic membrane neurotransmitter receptor levels | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred regulation of postsynaptic receptor levels. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. |
| GO:0099073 mitochondrion-derived vesicle | IDA PMID:24446486 Parkin and PINK1 function in a vesicular trafficking pathway... | KEEP AS NON CORE | Summary: Parkin is associated with mitochondria-derived vesicles. Reason: Non-core location. Supporting Evidence: PMID:24446486 Wild-type but not PD-linked mutant parkin supports the biogenesis of a population of mitochondria-derived vesicles (MDVs), which bud off mitochondria and contain a specific repertoire of cargo proteins. |
| GO:0099074 mitochondrion to lysosome vesicle-mediated transport | IDA PMID:24446486 Parkin and PINK1 function in a vesicular trafficking pathway... | KEEP AS NON CORE | Summary: Parkin supports formation of mitochondria-derived vesicles that deliver oxidized cargo to lysosomes. Reason: Experimentally supported, distinct quality-control pathway; non-core. Supporting Evidence: PMID:24446486 Wild-type but not PD-linked mutant parkin supports the biogenesis of a population of mitochondria-derived vesicles (MDVs), which bud off mitochondria and contain a specific repertoire of cargo proteins. |
| GO:0140251 regulation protein catabolic process at presynapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred regulation of presynaptic protein catabolism. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. |
| GO:1900242 regulation of synaptic vesicle endocytosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Parkin interacts with endophilin and regulates synaptic vesicle endocytosis (ortholog transfer). Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. |
| GO:1900407 regulation of cellular response to oxidative stress | IDA PMID:24446486 Parkin and PINK1 function in a vesicular trafficking pathway... | KEEP AS NON CORE | Summary: Parkin regulates the response to oxidative stress (e.g. MDV formation, dopamine oxidation). Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:24446486 Wild-type but not PD-linked mutant parkin supports the biogenesis of a population of mitochondria-derived vesicles (MDVs), which bud off mitochondria and contain a specific repertoire of cargo proteins. |
| GO:1900407 regulation of cellular response to oxidative stress | IMP PMID:22314364 Parkin controls dopamine utilization in human midbrain dopam... | KEEP AS NON CORE | Summary: Parkin regulates the response to oxidative stress (e.g. MDV formation, dopamine oxidation). Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:24446486 Wild-type but not PD-linked mutant parkin supports the biogenesis of a population of mitochondria-derived vesicles (MDVs), which bud off mitochondria and contain a specific repertoire of cargo proteins. |
| GO:1900407 regulation of cellular response to oxidative stress | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Parkin regulates the response to oxidative stress (e.g. MDV formation, dopamine oxidation). Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:24446486 Wild-type but not PD-linked mutant parkin supports the biogenesis of a population of mitochondria-derived vesicles (MDVs), which bud off mitochondria and contain a specific repertoire of cargo proteins. |
| GO:1901526 positive regulation of mitophagy | IDA PMID:20098416 PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p6... | ACCEPT | Summary: Parkin promotes mitophagy by ubiquitinating outer-membrane proteins (e.g. VDAC1) that recruit p62/SQSTM1. Reason: Core. Supporting Evidence: PMID:20098416 Strikingly, we identified VDAC1 (voltage-dependent anion channel 1) as a target for Parkin-mediated Lys 27 poly-ubiquitylation and mitophagy. |
| GO:1901526 positive regulation of mitophagy | IDA PMID:26310625 F-box protein 7 mutations promote protein aggregation in mit... | ACCEPT | Summary: Parkin promotes mitophagy by ubiquitinating outer-membrane proteins (e.g. VDAC1) that recruit p62/SQSTM1. Reason: Core. Supporting Evidence: PMID:20098416 Strikingly, we identified VDAC1 (voltage-dependent anion channel 1) as a target for Parkin-mediated Lys 27 poly-ubiquitylation and mitophagy. |
| GO:1901526 positive regulation of mitophagy | IEA GO_REF:0000107 | ACCEPT | Summary: Parkin promotes mitophagy by ubiquitinating outer-membrane proteins (e.g. VDAC1) that recruit p62/SQSTM1. Reason: Core. Supporting Evidence: PMID:20098416 Strikingly, we identified VDAC1 (voltage-dependent anion channel 1) as a target for Parkin-mediated Lys 27 poly-ubiquitylation and mitophagy. |
| GO:1901800 positive regulation of proteasomal protein catabolic process | IGI PMID:23858059 Parkin-dependent degradation of the F-box protein Fbw7Ξ² prom... | ACCEPT | Summary: Parkin targets substrates such as Fbw7beta for proteasomal degradation. Reason: Direct consequence of Parkin E3 ligase activity. Supporting Evidence: PMID:23858059 Specifically, parkin targets the SCF substrate adapter Fbw7Ξ² for proteasomal degradation. |
| GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway | IDA PMID:11439185 An unfolded putative transmembrane polypeptide, which can le... | KEEP AS NON CORE | Summary: Parkin protects cells from ER/unfolded-protein-stress-induced death through ubiquitination of misfolded substrates and other mechanisms. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:10973942 Furthermore, overexpression of Parkin, but not a set of mutants without the E3 activity, specifically suppressed unfolded protein stress-induced cell death. PMID:11439185 Parkin specifically ubiquitinates this receptor in the presence of ubiquitin-conjugating enzymes resident in the endoplasmic reticulum and promotes the degradation of insoluble Pael receptor, resulting in suppression of the cell death induced by Pael receptor overexpression. |
| GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway | IDA PMID:12150907 CHIP is associated with Parkin, a gene responsible for famil... | KEEP AS NON CORE | Summary: Parkin protects cells from ER/unfolded-protein-stress-induced death through ubiquitination of misfolded substrates and other mechanisms. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:10973942 Furthermore, overexpression of Parkin, but not a set of mutants without the E3 activity, specifically suppressed unfolded protein stress-induced cell death. PMID:11439185 Parkin specifically ubiquitinates this receptor in the presence of ubiquitin-conjugating enzymes resident in the endoplasmic reticulum and promotes the degradation of insoluble Pael receptor, resulting in suppression of the cell death induced by Pael receptor overexpression. |
| GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway | IDA PMID:23453807 The E3 ligase parkin maintains mitochondrial integrity by in... | KEEP AS NON CORE | Summary: Parkin protects cells from ER/unfolded-protein-stress-induced death through ubiquitination of misfolded substrates and other mechanisms. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:10973942 Furthermore, overexpression of Parkin, but not a set of mutants without the E3 activity, specifically suppressed unfolded protein stress-induced cell death. PMID:11439185 Parkin specifically ubiquitinates this receptor in the presence of ubiquitin-conjugating enzymes resident in the endoplasmic reticulum and promotes the degradation of insoluble Pael receptor, resulting in suppression of the cell death induced by Pael receptor overexpression. |
| GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Parkin protects cells from ER/unfolded-protein-stress-induced death through ubiquitination of misfolded substrates and other mechanisms. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:10973942 Furthermore, overexpression of Parkin, but not a set of mutants without the E3 activity, specifically suppressed unfolded protein stress-induced cell death. PMID:11439185 Parkin specifically ubiquitinates this receptor in the presence of ubiquitin-conjugating enzymes resident in the endoplasmic reticulum and promotes the degradation of insoluble Pael receptor, resulting in suppression of the cell death induced by Pael receptor overexpression. |
| GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway | IMP PMID:10973942 Parkin suppresses unfolded protein stress-induced cell death... | KEEP AS NON CORE | Summary: Parkin protects cells from ER/unfolded-protein-stress-induced death through ubiquitination of misfolded substrates and other mechanisms. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:10973942 Furthermore, overexpression of Parkin, but not a set of mutants without the E3 activity, specifically suppressed unfolded protein stress-induced cell death. PMID:11439185 Parkin specifically ubiquitinates this receptor in the presence of ubiquitin-conjugating enzymes resident in the endoplasmic reticulum and promotes the degradation of insoluble Pael receptor, resulting in suppression of the cell death induced by Pael receptor overexpression. |
| GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway | IMP PMID:21113145 Parkin is transcriptionally regulated by ATF4: evidence for ... | KEEP AS NON CORE | Summary: Parkin protects cells from ER/unfolded-protein-stress-induced death through ubiquitination of misfolded substrates and other mechanisms. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:10973942 Furthermore, overexpression of Parkin, but not a set of mutants without the E3 activity, specifically suppressed unfolded protein stress-induced cell death. PMID:11439185 Parkin specifically ubiquitinates this receptor in the presence of ubiquitin-conjugating enzymes resident in the endoplasmic reticulum and promotes the degradation of insoluble Pael receptor, resulting in suppression of the cell death induced by Pael receptor overexpression. |
| GO:1902254 negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator | IMP PMID:23985028 S-Nitrosylation of parkin as a novel regulator of p53-mediat... | KEEP AS NON CORE | Summary: Parkin represses p53 and p53-dependent neuronal apoptosis, which S-nitrosylation of Parkin inhibits. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:23985028 Mutations in the gene encoding parkin, a neuroprotective protein with dual functions as an E3 ubiquitin ligase and transcriptional repressor of p53, are linked to familial forms of Parkinson's disease (PD). |
| GO:1902530 positive regulation of protein linear polyubiquitination | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Parkin is recruited to LUBAC and increases linear ubiquitination of NEMO. Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:23453807 Under cellular stress, parkin is recruited to the linear ubiquitin assembly complex and increases linear ubiquitination of NF-ΞΊB essential modulator (NEMO), which is essential for canonical NF-ΞΊB signaling. |
| GO:1902530 positive regulation of protein linear polyubiquitination | IGI PMID:23453807 The E3 ligase parkin maintains mitochondrial integrity by in... | KEEP AS NON CORE | Summary: Parkin is recruited to LUBAC and increases linear ubiquitination of NEMO. Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:23453807 Under cellular stress, parkin is recruited to the linear ubiquitin assembly complex and increases linear ubiquitination of NF-ΞΊB essential modulator (NEMO), which is essential for canonical NF-ΞΊB signaling. |
| GO:1902803 regulation of synaptic vesicle transport | NAS PMID:21563316 Synaptic vesicle trafficking and Parkinson's disease. | MARK AS OVER ANNOTATED | Summary: Review statement on PD genes and synaptic vesicle trafficking. Reason: Speculative review statement. |
| GO:1903265 positive regulation of tumor necrosis factor-mediated signaling pathway | IDA PMID:23453807 The E3 ligase parkin maintains mitochondrial integrity by in... | KEEP AS NON CORE | Summary: Parkin promotes TNF-induced NF-kappaB activation through NEMO linear ubiquitination. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:23453807 Under cellular stress, parkin is recruited to the linear ubiquitin assembly complex and increases linear ubiquitination of NF-ΞΊB essential modulator (NEMO), which is essential for canonical NF-ΞΊB signaling. |
| GO:1903351 cellular response to dopamine | TAS PMID:23626584 Structure and Function of Parkin, PINK1, and DJ-1, the Three... | MARK AS OVER ANNOTATED | Summary: Dopamine covalently modifies and inactivates Parkin (review statement). Reason: Being modified by dopamine is not a dedicated response to dopamine. Supporting Evidence: PMID:16227987 These findings show a vulnerability of parkin to modification by dopamine, the principal transmitter lost in Parkinson disease, suggesting a mechanism for the progressive loss of parkin function in dopaminergic neurons during aging and sporadic Parkinson disease. |
| GO:1903377 negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway | IDA PMID:17314283 Parkin mediates neuroprotection through activation of Ikappa... | KEEP AS NON CORE | Summary: Parkin protects neurons from oxidative-stress-induced apoptosis (e.g. via NF-kappaB signalling). Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:17314283 Finally, we present evidence that parkin interacts with and promotes degradation-independent ubiquitylation of IKKgamma/NEMO (NF-kappaB essential modifier) and TRAF2 [TNF (tumor necrosis factor) receptor-associated factor 2], two critical components of the NF-kappaB pathway. |
| GO:1903377 negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Parkin protects neurons from oxidative-stress-induced apoptosis (e.g. via NF-kappaB signalling). Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:17314283 Finally, we present evidence that parkin interacts with and promotes degradation-independent ubiquitylation of IKKgamma/NEMO (NF-kappaB essential modifier) and TRAF2 [TNF (tumor necrosis factor) receptor-associated factor 2], two critical components of the NF-kappaB pathway. |
| GO:1903382 negative regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred protection of neurons from ER-stress-induced apoptosis. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. |
| GO:1903427 negative regulation of reactive oxygen species biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred negative regulation of ROS production. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. |
| GO:1903530 regulation of secretion by cell | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Broad electronic term (e.g. exosome secretion). Reason: Broad. |
| GO:1903542 negative regulation of exosomal secretion | IMP PMID:26911690 Parkin Modulates Endosomal Organization and Function of the ... | KEEP AS NON CORE | Summary: Parkin deficiency increases exosome release, via loss of Rab7 ubiquitination. Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:26911690 We also found increased formation of intraluminal vesicles coupled with enhanced release of exosomes in the presence of mutant Parkin. |
| GO:1903747 obsolete regulation of protein localization to mitochondrion | NAS PMID:20890124 p62/SQSTM1 is required for Parkin-induced mitochondrial clus... | REMOVE | Summary: NAS annotation, from a study of p62-dependent mitochondrial clustering, to a term GOA labels obsolete. Reason: GOA labels the term obsolete. The cited study concerns Parkin-induced p62 recruitment and mitochondrial clustering, which is covered by the mitophagy and protein ubiquitination annotations. Supporting Evidence: PMID:20890124 These results demonstrate that mitochondria are aggregated by p62, following its recruitment by Parkin in a VDAC1-independent manner. |
| GO:1903861 positive regulation of dendrite extension | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred positive regulation of dendrite extension. Reason: Ortholog-transferred (Ensembl Compara) annotation, most likely from a rodent phenotype or expression study. Parkin loss causes broad neuronal and mitochondrial dysfunction, so many readouts change secondarily. That does not show Parkin performs a step of this process. |
| GO:1904049 negative regulation of spontaneous neurotransmitter secretion | IMP PMID:22314364 Parkin controls dopamine utilization in human midbrain dopam... | KEEP AS NON CORE | Summary: Loss of Parkin in human DA neurons increases spontaneous dopamine release. Reason: Experimental but indirect and non-core. Supporting Evidence: PMID:22314364 We demonstrate that loss of parkin in human midbrain DA neurons greatly increases the transcription of monoamine oxidases and oxidative stress, significantly reduces DA uptake and increases spontaneous DA release. |
| GO:1904643 response to curcumin | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred response to curcumin. Reason: Ortholog-transferred (Ensembl Compara) annotation, most likely from a rodent phenotype or expression study. Parkin loss causes broad neuronal and mitochondrial dysfunction, so many readouts change secondarily. That does not show Parkin performs a step of this process. |
| GO:1904845 cellular response to L-glutamine | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred cellular response to L-glutamine. Reason: Ortholog-transferred (Ensembl Compara) annotation, most likely from a rodent phenotype or expression study. Parkin loss causes broad neuronal and mitochondrial dysfunction, so many readouts change secondarily. That does not show Parkin performs a step of this process. |
| GO:1904881 cellular response to hydrogen sulfide | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred cellular response to hydrogen sulfide. Reason: Ortholog-transferred (Ensembl Compara) annotation, most likely from a rodent phenotype or expression study. Parkin loss causes broad neuronal and mitochondrial dysfunction, so many readouts change secondarily. That does not show Parkin performs a step of this process. |
| GO:1905091 positive regulation of type 2 mitophagy | IDA PMID:20457763 Disease-causing mutations in parkin impair mitochondrial ubi... | ACCEPT | Summary: Parkin promotes depolarization-induced mitophagy; AR-JP mutations impair it. Reason: Core. Supporting Evidence: PMID:20457763 Importantly, we show that AR-JP-causing parkin mutations are defective in supporting mitophagy due to distinct defects at recognition, transportation, or ubiquitination of impaired mitochondria, thereby implicating mitophagy defects in the development of parkinsonism. PMID:20871098 The ubiquitination of several mitochondrial proteins, including mitofusin 1 and mitofusin 2, were detected within 3 h of CCCP treatment. |
| GO:1905091 positive regulation of type 2 mitophagy | IMP PMID:20871098 Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/par... | ACCEPT | Summary: Parkin promotes depolarization-induced mitophagy; AR-JP mutations impair it. Reason: Core. Supporting Evidence: PMID:20457763 Importantly, we show that AR-JP-causing parkin mutations are defective in supporting mitophagy due to distinct defects at recognition, transportation, or ubiquitination of impaired mitochondria, thereby implicating mitophagy defects in the development of parkinsonism. PMID:20871098 The ubiquitination of several mitochondrial proteins, including mitofusin 1 and mitofusin 2, were detected within 3 h of CCCP treatment. |
| GO:1905091 positive regulation of type 2 mitophagy | IMP PMID:23212910 Phosphatase and tensin homolog (PTEN)-induced putative kinas... | ACCEPT | Summary: Parkin promotes depolarization-induced mitophagy; AR-JP mutations impair it. Reason: Core. Supporting Evidence: PMID:20457763 Importantly, we show that AR-JP-causing parkin mutations are defective in supporting mitophagy due to distinct defects at recognition, transportation, or ubiquitination of impaired mitochondria, thereby implicating mitophagy defects in the development of parkinsonism. PMID:20871098 The ubiquitination of several mitochondrial proteins, including mitofusin 1 and mitofusin 2, were detected within 3 h of CCCP treatment. |
| GO:1905232 cellular response to L-glutamate | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred cellular response to L-glutamate. Reason: Ortholog-transferred (Ensembl Compara) annotation, most likely from a rodent phenotype or expression study. Parkin loss causes broad neuronal and mitochondrial dysfunction, so many readouts change secondarily. That does not show Parkin performs a step of this process. |
| GO:1905281 positive regulation of retrograde transport, endosome to Golgi | NAS PMID:26911690 Parkin Modulates Endosomal Organization and Function of the ... | KEEP AS NON CORE | Summary: Parkin regulates endosome-to-Golgi retromer function via Rab7. Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:26911690 To elucidate the molecular mechanism of these alterations in the endocytic pathway in Parkin-deficient cells, we found that Parkin regulates the levels and activity of Rab7 by promoting its ubiquitination on lysine 38 residue. |
| GO:1905366 negative regulation of intralumenal vesicle formation | IMP PMID:26911690 Parkin Modulates Endosomal Organization and Function of the ... | KEEP AS NON CORE | Summary: Mutant Parkin increases intraluminal vesicle formation. Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:26911690 We also found increased formation of intraluminal vesicles coupled with enhanced release of exosomes in the presence of mutant Parkin. |
| GO:1905477 positive regulation of protein localization to membrane | IC PMID:26911690 Parkin Modulates Endosomal Organization and Function of the ... | KEEP AS NON CORE | Summary: Parkin-dependent Rab7 ubiquitination promotes Rab7 membrane association. Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:26911690 To elucidate the molecular mechanism of these alterations in the endocytic pathway in Parkin-deficient cells, we found that Parkin regulates the levels and activity of Rab7 by promoting its ubiquitination on lysine 38 residue. |
| GO:1905477 positive regulation of protein localization to membrane | IMP PMID:26911690 Parkin Modulates Endosomal Organization and Function of the ... | KEEP AS NON CORE | Summary: Parkin-dependent Rab7 ubiquitination promotes Rab7 membrane association. Reason: A downstream consequence of Parkin ubiquitinating a particular substrate. Experimentally supported but not part of the core mitophagy function. Supporting Evidence: PMID:26911690 To elucidate the molecular mechanism of these alterations in the endocytic pathway in Parkin-deficient cells, we found that Parkin regulates the levels and activity of Rab7 by promoting its ubiquitination on lysine 38 residue. |
| GO:1990000 amyloid fibril formation | TAS Reactome:R-HSA-977225 | MARK AS OVER ANNOTATED | Summary: Reactome places Parkin in the amyloid fibril formation pathway. Reason: Parkin does not perform amyloid fibril formation; this reflects pathway membership (it ubiquitinates aggregation-prone substrates), not participation. |
| GO:1990381 ubiquitin-specific protease binding | IPI PMID:24063750 Ataxin-3 is a multivalent ligand for the parkin Ubl domain. | KEEP AS NON CORE | Summary: The Parkin Ubl domain binds the UIMs of the deubiquitinase ataxin-3. Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. |
| GO:1990444 F-box domain binding | IPI PMID:12628165 Parkin is a component of an SCF-like ubiquitin ligase comple... | KEEP AS NON CORE | Summary: Parkin associates with the F-box protein hSel-10/FBXW7. Reason: A binding term reflecting an interaction with a substrate, regulator or partner. The interaction is plausible, but the informative activity is Parkin E3 ubiquitin ligase activity. Supporting Evidence: PMID:12628165 Here we show that parkin functions in a multiprotein ubiquitin ligase complex that includes the F-box/WD repeat protein hSel-10 and Cullin-1. |
| GO:1990452 Parkin-FBXW7-Cul1 ubiquitin ligase complex | IPI PMID:12628165 Parkin is a component of an SCF-like ubiquitin ligase comple... | KEEP AS NON CORE | Summary: Parkin forms a multiprotein ligase complex with FBXW7 (hSel-10) and Cullin-1 that targets cyclin E. Reason: Experimentally supported complex, but most Parkin activity (in mitophagy) is as a monomeric RBR E3 ligase. Supporting Evidence: PMID:12628165 Here we show that parkin functions in a multiprotein ubiquitin ligase complex that includes the F-box/WD repeat protein hSel-10 and Cullin-1. |
| GO:2000377 regulation of reactive oxygen species metabolic process | IMP PMID:18541373 Parkin is ubiquitinated by Nrdp1 and abrogates Nrdp1-induced... | KEEP AS NON CORE | Summary: Parkin abrogates Nrdp1-induced ROS production. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:18541373 In addition, we demonstrated that overexpression of Nrdp1 increased the production of reactive oxygen species (ROS), which was abrogated by co-expression of Parkin. |
| GO:2000378 negative regulation of reactive oxygen species metabolic process | IGI PMID:18541373 Parkin is ubiquitinated by Nrdp1 and abrogates Nrdp1-induced... | KEEP AS NON CORE | Summary: Parkin abrogates Nrdp1-induced ROS production. Reason: Parkin has many reported neuroprotective, anti-apoptotic and substrate-specific roles in neurons. Most are linked to its E3 ligase activity on individual substrates. They are genuine but secondary to its core, conserved role as the PINK1-activated E3 ligase for mitochondrial quality control. Supporting Evidence: PMID:18541373 In addition, we demonstrated that overexpression of Nrdp1 increased the production of reactive oxygen species (ROS), which was abrogated by co-expression of Parkin. |
| GO:2001171 positive regulation of ATP biosynthetic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred positive regulation of ATP biosynthesis. Reason: Ortholog-transferred (Ensembl Compara) annotation, most likely from a rodent phenotype or expression study. Parkin loss causes broad neuronal and mitochondrial dysfunction, so many readouts change secondarily. That does not show Parkin performs a step of this process. |
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Download this section (compressed HTML)Q: Which of the many reported non-mitochondrial Parkin substrates (PARIS, Pael-R, synphilin-1, Fbw7beta, RIPK3, NEMO) are physiologically relevant in human dopaminergic neurons at endogenous Parkin levels, compared with its mitophagy role?
Q: Is Parkin transcriptional repression of TP53 a genuine nuclear activity of Parkin or an indirect effect of its ligase activity?
Experiment: Use ubiquitin-remnant (diGly) proteomics in iPSC-derived DA neurons from PRKN-null versus isogenic controls, with and without mitochondrial stress and with PINK1 knockout, to define the endogenous PINK1-dependent and PINK1-independent Parkin substrate repertoire.
Hypothesis: Endogenous Parkin activity in dopaminergic neurons in vivo is predominantly mitochondrial and PINK1-dependent.
Type: quantitative ubiquitylomics
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