park encodes Drosophila parkin, a cytosolic RBR (RING-between-RING) E3 ubiquitin ligase and the ortholog of human PRKN. It has an N-terminal ubiquitin-like domain followed by RING0, RING1, IBR and RING2 zinc-binding domains. It binds E2 enzymes through RING1 and transfers ubiquitin to substrates through a thioester with the RING2 catalytic cysteine (Cys449). Parkin is autoinhibited at rest. When mitochondria lose membrane potential, PINK1 phosphorylates parkin (Ser94 in the Ubl domain) and ubiquitin, and parkin is recruited from the cytosol to the mitochondrial surface and activated. There it mono- and polyubiquitinates outer membrane proteins such as mitofusin (Marf), Porin/VDAC and Miro. This limits fusion of damaged mitochondria and marks them for autophagic removal (mitophagy). It also ubiquitinates the transcriptional repressor Paris for proteasomal degradation, which supports mitochondrial biogenesis. Loss of park causes mitochondrial swelling and dysfunction in tissues with high energy demand: degeneration of indirect flight muscle, defective spermatid mitochondrial derivatives and male sterility, female sterility, degeneration of dopaminergic neurons, locomotor defects and reduced lifespan.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000151 ubiquitin ligase complex | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA part_of ubiquitin ligase complex from the RBR family node PTN000188395. Reason: The node is seeded by ARIH1, ARIH2, C. elegans pdr-1 and human PRKN. Stable membership of a ubiquitin ligase complex is an Ariadne-clade property (ARIH1/2 work bound to neddylated cullin-RING ligases). Fly parkin is a single-subunit RBR E3 that engages E2s only transiently through RING1; there is no fly evidence that it is a stable subunit of a larger ligase complex. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000188395 SUPPORTS SOURCE BUT NOT TARGET RBR family node; complex membership is grounded mainly by Ariadne-clade members (ARIH1, ARIH2), which partner cullin-RING ligases. Parkin-clade proteins act as single-subunit E3s. UniProtKB:O60260 SOURCE WEAK OR INFERRED Human PRKN complex membership rests on an SCF-like complex report that has not been shown for the fly protein. Supporting Evidence: PMID:17456438 D. melanogaster Parkin as an E3 ligase interacts with UbcH8 through its RING1 domain file:genes/DROME/park/park-uniprot.txt They interact with E2 conjugating enzymes and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer |
| GO:0000209 protein polyubiquitination | IDA PMID:17456438 Drosophila melanogaster Parkin ubiquitinates peanut and sept... | ACCEPT | Summary: Parkin polyubiquitinates septins in vitro (IDA). Reason: Fly parkin ubiquitinated peanut and Septin1 in E2-dependent assays; polyubiquitination of substrates is a direct product of its E3 activity. Abstract-only paper, curator call deferred to. Supporting Evidence: PMID:17456438 peanut and septin1, D. melanogaster septin proteins, were also ubiquitinated by D. melanogaster Parkin PMID:17456438 D. melanogaster Parkin exhibited UbcH8-dependent E3 ubiquitin-protein ligase activity |
| GO:0000209 protein polyubiquitination | IMP PMID:32047033 Decision between mitophagy and apoptosis by Parkin via VDAC1... | ACCEPT | Summary: Parkin polyubiquitinates Porin/VDAC (IMP). Reason: Porin polyubiquitination by parkin is shown in S2 cells; parkin catalyses this ubiquitination. Supporting Evidence: PMID:32047033 Porin mono- and polyubiquitination by Parkin occurred in a highly conserved manner PMID:32047033 VDAC1 can be either mono- or polyubiquitinated by Parkin in a PINK1-dependent manner |
| GO:0000266 mitochondrial fission | IGI PMID:18230723 The PINK1/Parkin pathway regulates mitochondrial morphology. | MODIFY | Summary: IGI mitochondrial fission from drp1/Opa1/Marf genetic interactions. Reason: Parkin does not execute mitochondrial fission; it is not part of the Drp1 fission machinery. The genetic interactions in PMID:18230723 (drp1, Opa1, Marf dosage) show that the PINK1/parkin pathway promotes fission (or limits fusion), which is a regulatory role. The correct term is GO:0090141 positive regulation of mitochondrial fission, which the gene already carries from PMID:18799731 and PMID:20194754. Proposed replacements: positive regulation of mitochondrial fission Supporting Evidence: PMID:18230723 Our studies suggest that the PINK1/Parkin pathway promotes mitochondrial fission and that the loss of mitochondrial and tissue integrity in PINK1 and parkin mutants derives from reduced mitochondrial fission PMID:18799731 These results suggest that pink1 and parkin are likely not core components of the drp1-mediated mitochondrial fission machinery |
| GO:0000266 mitochondrial fission | IGI PMID:18230723 The PINK1/Parkin pathway regulates mitochondrial morphology. | MODIFY | Summary: IGI mitochondrial fission from drp1/Opa1/Marf genetic interactions. Reason: Parkin does not execute mitochondrial fission; it is not part of the Drp1 fission machinery. The genetic interactions in PMID:18230723 (drp1, Opa1, Marf dosage) show that the PINK1/parkin pathway promotes fission (or limits fusion), which is a regulatory role. The correct term is GO:0090141 positive regulation of mitochondrial fission, which the gene already carries from PMID:18799731 and PMID:20194754. Proposed replacements: positive regulation of mitochondrial fission Supporting Evidence: PMID:18230723 Our studies suggest that the PINK1/Parkin pathway promotes mitochondrial fission and that the loss of mitochondrial and tissue integrity in PINK1 and parkin mutants derives from reduced mitochondrial fission PMID:18799731 These results suggest that pink1 and parkin are likely not core components of the drp1-mediated mitochondrial fission machinery |
| GO:0000266 mitochondrial fission | IGI PMID:18230723 The PINK1/Parkin pathway regulates mitochondrial morphology. | MODIFY | Summary: IGI mitochondrial fission from drp1/Opa1/Marf genetic interactions. Reason: Parkin does not execute mitochondrial fission; it is not part of the Drp1 fission machinery. The genetic interactions in PMID:18230723 (drp1, Opa1, Marf dosage) show that the PINK1/parkin pathway promotes fission (or limits fusion), which is a regulatory role. The correct term is GO:0090141 positive regulation of mitochondrial fission, which the gene already carries from PMID:18799731 and PMID:20194754. Proposed replacements: positive regulation of mitochondrial fission Supporting Evidence: PMID:18230723 Our studies suggest that the PINK1/Parkin pathway promotes mitochondrial fission and that the loss of mitochondrial and tissue integrity in PINK1 and parkin mutants derives from reduced mitochondrial fission PMID:18799731 These results suggest that pink1 and parkin are likely not core components of the drp1-mediated mitochondrial fission machinery |
| GO:0000423 mitophagy | IBA GO_REF:0000033 | ACCEPT | Summary: IBA mitophagy (parkin clade node PTN000188399). Reason: Core process. Fly parkin is required for depolarization-induced mitophagy in S2 cells and for mitochondrial turnover in vivo; the IBA is consistent with the fly evidence. Supporting Evidence: PMID:20194754 Parkin was also required for CCCP-induced mitophagy in Drosophila cells PMID:23509287 parkin null mutants showed a significant overall slowing of mitochondrial protein turnover |
| GO:0000423 mitophagy | IEA GO_REF:0000117 | ACCEPT | Summary: IEA (ARBA) mitophagy. Reason: Correct; fly experimental data independently support parkin in mitophagy. The term is kept at mitophagy because the in vivo mitophagy contexts (developmental clearance, basal turnover) are not shown to be depolarization-initiated type 2 mitophagy. Supporting Evidence: PMID:20194754 Parkin was also required for CCCP-induced mitophagy in Drosophila cells PMID:23509287 Our findings show that the PINK1-Parkin pathway promotes mitophagy in vivo |
| GO:0000423 mitophagy | IMP PMID:24192653 Mitochondrial contagion induced by Parkin deficiency in Dros... | ACCEPT | Summary: IMP mitophagy in heart tubes. Reason: Parkin loss in fly cardiomyocytes impairs mitophagic culling of mitochondria. Supporting Evidence: PMID:24192653 Parkin deficiency and resulting mitophagic disruption produces cardiomyopathy |
| GO:0000423 mitophagy | IMP PMID:37633267 PINK1, Keap1, and Rtnl1 regulate selective clearance of endo... | ACCEPT | Summary: IMP mitophagy in developmental intestinal mitochondrial clearance. Reason: Parkin is required for developmental mitochondrial clearance by autophagy in the fly intestine. Supporting Evidence: PMID:37633267 The E3 ubiquitin ligase Parkin functions downstream of PINK1 and is required for mitochondrial clearance while having the opposite function in ER clearance |
| GO:0004842 ubiquitin-protein transferase activity | IEA GO_REF:0000002 | MODIFY | Summary: IEA ubiquitin-protein transferase activity from InterPro. Reason: Correct but general. Parkin is an RBR E3 ubiquitin ligase (EC 2.3.2.31) with a catalytic Cys449, and the gene carries GO:0061630 ubiquitin protein ligase activity from several experimental rows. Proposed replacements: ubiquitin protein ligase activity Supporting Evidence: PMID:17456438 D. melanogaster Parkin exhibited UbcH8-dependent E3 ubiquitin-protein ligase activity PMID:23770917 A single cysteine residue (C449; C431 in human) is exposed on the Ξ²2βΞ²3 loop file:genes/DROME/park/park-uniprot.txt Belongs to the RBR family. Parkin subfamily. |
| GO:0005515 protein binding | IPI PMID:20194754 Drosophila parkin requires PINK1 for mitochondrial transloca... | REMOVE | Summary: IPI protein binding with Marf. Reason: Bare protein binding is uninformative. The Marf interaction is the enzyme-substrate relationship already captured by ubiquitin protein ligase activity and negative regulation of mitochondrial fusion. Supporting Evidence: PMID:20194754 Immunoprecipitation assays revealed that upon coexpression Parkin-GFP is detected in precipitates of Mfn-Flag |
| GO:0005515 protein binding | IPI PMID:24898855 MUL1 acts in parallel to the PINK1/parkin pathway in regulat... | REMOVE | Summary: IPI protein binding with Marf. Reason: Bare protein binding is uninformative; Marf is a parkin ubiquitination substrate, captured elsewhere. Supporting Evidence: PMID:24898855 Parkin was used as a positive control and co-immunoprecipitated with Mfn as previously reported |
| GO:0005515 protein binding | IPI PMID:32138754 PARIS induced defects in mitochondrial biogenesis drive dopa... | REMOVE | Summary: IPI protein binding with Paris. Reason: Bare protein binding is uninformative; Paris is a parkin ubiquitination substrate, captured by ubiquitin protein ligase activity. Supporting Evidence: PMID:32138754 parkin mediated ubiquitination of dPARIS targets it for proteosomal degradation, thereby promoting DA neuron survival in vivo |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: IBA cytoplasm. Reason: Parkin resides diffusely in the cytoplasm until recruited to damaged mitochondria. The imaging assays cannot separate cytosol from other cytoplasmic compartments, so cytoplasm is as precise as these rows allow; cytosol is captured by separate rows. Supporting Evidence: PMID:20194754 In wild-type Drosophila cells, Parkin-GFP typically showed a diffuse localization throughout the cytoplasm with occasional accumulations at mitochondria PMID:24901221 The Parkin and PINK1 genes encode a cytosolic ubiquitin-ligase |
| GO:0005737 cytoplasm | IDA PMID:16002472 Parkin negatively regulates JNK pathway in the dopaminergic ... | ACCEPT | Summary: IDA cytoplasm (DA neurons; abstract-only paper). Reason: Parkin resides diffusely in the cytoplasm until recruited to damaged mitochondria. The imaging assays cannot separate cytosol from other cytoplasmic compartments, so cytoplasm is as precise as these rows allow; cytosol is captured by separate rows. Curator call on an abstract-only paper deferred to. Supporting Evidence: PMID:20194754 In wild-type Drosophila cells, Parkin-GFP typically showed a diffuse localization throughout the cytoplasm with occasional accumulations at mitochondria |
| GO:0005737 cytoplasm | IDA PMID:20194754 Drosophila parkin requires PINK1 for mitochondrial transloca... | ACCEPT | Summary: IDA cytoplasm (Parkin-GFP in S2 cells). Reason: Parkin resides diffusely in the cytoplasm until recruited to damaged mitochondria. The imaging assays cannot separate cytosol from other cytoplasmic compartments, so cytoplasm is as precise as these rows allow; cytosol is captured by separate rows. Supporting Evidence: PMID:20194754 In wild-type Drosophila cells, Parkin-GFP typically showed a diffuse localization throughout the cytoplasm with occasional accumulations at mitochondria |
| GO:0005737 cytoplasm | IDA PMID:20869429 Diminution of eIF4E activity suppresses parkin mutant phenot... | ACCEPT | Summary: IDA cytoplasm (oocyte). Reason: Parkin resides diffusely in the cytoplasm until recruited to damaged mitochondria. The imaging assays cannot separate cytosol from other cytoplasmic compartments, so cytoplasm is as precise as these rows allow; cytosol is captured by separate rows. Parkin co-localizes with eIF4E at the oocyte posterior. Supporting Evidence: PMID:20869429 Parkin and eIF4E interact in vitro and co-localize at the posterior end of developing oocytes |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: IEA (ARBA) cytoplasm. Reason: Parkin resides diffusely in the cytoplasm until recruited to damaged mitochondria. The imaging assays cannot separate cytosol from other cytoplasmic compartments, so cytoplasm is as precise as these rows allow; cytosol is captured by separate rows. Supporting Evidence: PMID:20194754 In wild-type Drosophila cells, Parkin-GFP typically showed a diffuse localization throughout the cytoplasm with occasional accumulations at mitochondria |
| GO:0005739 mitochondrion | IDA PMID:18957282 PINK1 controls mitochondrial localization of Parkin through ... | ACCEPT | Summary: IDA mitochondrion (PINK1-dependent translocation; abstract-only). Reason: Root organelle term. Parkin is recruited from the cytosol onto damaged mitochondria in a PINK1-dependent manner, where it ubiquitinates outer membrane proteins. Imaging assays resolve the organelle, not the sub-compartment. Supporting Evidence: PMID:18957282 Parkin phosphorylation by PINK1 on its linker region promotes its mitochondrial translocation |
| GO:0005739 mitochondrion | IDA PMID:20194754 Drosophila parkin requires PINK1 for mitochondrial transloca... | ACCEPT | Summary: IDA mitochondrion (Parkin-GFP after CCCP/paraquat). Reason: Root organelle term. Parkin is recruited from the cytosol onto damaged mitochondria in a PINK1-dependent manner, where it ubiquitinates outer membrane proteins. Imaging assays resolve the organelle, not the sub-compartment. Supporting Evidence: PMID:20194754 a large proportion of cells showed Parkin-GFP accumulated at or near mitochondria |
| GO:0005739 mitochondrion | IDA PMID:27906179 PINK1-dependent phosphorylation of PINK1 and Parkin is essen... | ACCEPT | Summary: IDA mitochondrion (eye discs, colocalization with PINK1 and TOM20). Reason: Root organelle term. Parkin is recruited from the cytosol onto damaged mitochondria in a PINK1-dependent manner, where it ubiquitinates outer membrane proteins. Imaging assays resolve the organelle, not the sub-compartment. Supporting Evidence: PMID:27906179 Although Parkin colocalized with wild-type PINK1 and TOM20 on mitochondria |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: IEA mitochondrion from UniProt subcellular location. Reason: Root organelle term. Parkin is recruited from the cytosol onto damaged mitochondria in a PINK1-dependent manner, where it ubiquitinates outer membrane proteins. Imaging assays resolve the organelle, not the sub-compartment. The UniProt location rests on the fly IDA papers, so the organelle claim holds. Supporting Evidence: file:genes/DROME/park/park-uniprot.txt Translocates from the cytosol to dysfunctional mitochondria that have lost their mitochondrial membrane potential; recruitment to mitochondria is Pink1-dependent |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA is_active_in endoplasmic reticulum. Reason: No fly study places parkin at the ER. The only ER link in fly is functional and opposite in sign: parkin restrains developmental ER clearance in the intestine, which says nothing about ER residence. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000188399 SUPPORTS SOURCE BUT NOT TARGET Parkin-clade node whose ER assertion is seeded only by mammalian PRKN (human, rat). UniProtKB:O60260 SOURCE WEAK OR INFERRED Human PRKN ER localization comes largely from overexpression and substrate (e.g. Pael-R) context; no fly counterpart. Supporting Evidence: PMID:37633267 The E3 ubiquitin ligase Parkin functions downstream of PINK1 and is required for mitochondrial clearance while having the opposite function in ER clearance file:genes/DROME/park/park-uniprot.txt Translocates from the cytosol to dysfunctional mitochondria that have lost their mitochondrial membrane potential; recruitment to mitochondria is Pink1-dependent file:genes/DROME/park/park-deep-research-manual.md no ER or Golgi localization has been reported for the fly protein in the cached literature |
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA is_active_in Golgi apparatus. Reason: No fly evidence for Golgi localization; the fly protein is cytosolic and recruited to mitochondria. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000188399 SUPPORTS SOURCE BUT NOT TARGET Parkin-clade node whose Golgi assertion is seeded only by mammalian PRKN (human, rat). UniProtKB:O60260 SOURCE WEAK OR INFERRED Human PRKN Golgi localization comes largely from overexpression and substrate (e.g. Pael-R) context; no fly counterpart. Supporting Evidence: file:genes/DROME/park/park-uniprot.txt Translocates from the cytosol to dysfunctional mitochondria that have lost their mitochondrial membrane potential; recruitment to mitochondria is Pink1-dependent file:genes/DROME/park/park-deep-research-manual.md no ER or Golgi localization has been reported for the fly protein in the cached literature |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: IBA is_active_in cytosol. Reason: Parkin is a cytosolic E3 that is recruited to mitochondria. Supporting Evidence: PMID:24901221 The Parkin and PINK1 genes encode a cytosolic ubiquitin-ligase file:genes/DROME/park/park-uniprot.txt Translocates from the cytosol to dysfunctional mitochondria that have lost their mitochondrial membrane potential; recruitment to mitochondria is Pink1-dependent |
| GO:0005829 cytosol | IEA GO_REF:0000120 | ACCEPT | Summary: IEA cytosol from UniProt subcellular location. Reason: Consistent with fly data. Supporting Evidence: PMID:24901221 The Parkin and PINK1 genes encode a cytosolic ubiquitin-ligase PMID:20194754 In wild-type Drosophila cells, Parkin-GFP typically showed a diffuse localization throughout the cytoplasm with occasional accumulations at mitochondria |
| GO:0006511 ubiquitin-dependent protein catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA ubiquitin-dependent protein catabolic process. Reason: Parkin ubiquitinates substrates (Marf, Paris) and thereby targets them for degradation; it performs the ubiquitin-tagging step. Supporting Evidence: PMID:32138754 parkin mediated ubiquitination of dPARIS targets it for proteosomal degradation, thereby promoting DA neuron survival in vivo PMID:20194754 Loss of Drosophila PINK1 or parkin causes an increase in Mfn abundance in vivo and concomitant elongation of mitochondria |
| GO:0006511 ubiquitin-dependent protein catabolic process | IMP PMID:20194754 Drosophila parkin requires PINK1 for mitochondrial transloca... | ACCEPT | Summary: IMP ubiquitin-dependent protein catabolic process (Marf accumulation in park mutants). Reason: Marf is ubiquitinated in a parkin-dependent manner and accumulates in park mutants. The degradation route for Marf is not resolved in this paper, so the general term is as precise as the evidence allows. Supporting Evidence: PMID:20194754 Loss of Drosophila PINK1 or parkin causes an increase in Mfn abundance in vivo and concomitant elongation of mitochondria PMID:20194754 PINK1 and Parkin mediate the ubiquitination of the profusion factor Mfn on the outer surface of mitochondria |
| GO:0006513 protein monoubiquitination | IDA PMID:29689197 Ari-1 Regulates Myonuclear Organization Together with Parkin... | ACCEPT | Summary: IDA protein monoubiquitination (Koi in vitro). Reason: Parkin monoubiquitinates Koi in vitro. Supporting Evidence: PMID:29689197 when performing in vitro ubiquitination assays, we found that Parkin can also mono-ubiquitinate Koi |
| GO:0006513 protein monoubiquitination | IMP PMID:32047033 Decision between mitophagy and apoptosis by Parkin via VDAC1... | ACCEPT | Summary: IMP protein monoubiquitination (Porin). Reason: Parkin monoubiquitinates Porin/VDAC; the T433N PD variant selectively loses this activity. Supporting Evidence: PMID:32047033 Porin mono- and polyubiquitination by Parkin occurred in a highly conserved manner PMID:32047033 VDAC1 can be either mono- or polyubiquitinated by Parkin in a PINK1-dependent manner |
| GO:0006950 response to stress | IEA GO_REF:0000117 | MODIFY | Summary: IEA (ARBA) response to stress. Reason: True but too broad. The specific stress response the gene carries with experimental support is response to oxidative stress. Proposed replacements: response to oxidative stress Supporting Evidence: PMID:21383066 We propose that Parkin and MTF-1 provide complementary functions in metal homeostasis, oxidative stress and other cellular stress responses PMID:20483372 our results demonstrate an important function of parkin in the protection against redox-active metals and pesticides |
| GO:0006979 response to oxidative stress | IMP PMID:15911761 Increased glutathione S-transferase activity rescues dopamin... | KEEP AS NON CORE | Summary: IMP response to oxidative stress (GstS1 modifier screen; abstract-only). Reason: Parkin mutant DA neuron loss is modified by GstS1, consistent with oxidative stress sensitivity; this is a downstream consequence of mitochondrial dysfunction, not a core activity. Supporting Evidence: PMID:15911761 Drosophila parkin mutants display degeneration of a subset of dopaminergic (DA) neurons in the brain |
| GO:0006979 response to oxidative stress | IMP PMID:21383066 The parkin mutant phenotype in the fly is largely rescued by... | KEEP AS NON CORE | Summary: IMP response to oxidative stress (MTF-1 interaction; abstract-only). Reason: Parkin mutants are rescued by MTF-1 and are sensitive to oxidative and metal stress; peripheral to the core E3/mitophagy function. Supporting Evidence: PMID:21383066 We propose that Parkin and MTF-1 provide complementary functions in metal homeostasis, oxidative stress and other cellular stress responses PMID:20483372 our results demonstrate an important function of parkin in the protection against redox-active metals and pesticides |
| GO:0007005 mitochondrion organization | IMP PMID:12642658 Mitochondrial pathology and apoptotic muscle degeneration in... | KEEP AS NON CORE | Summary: IMP mitochondrion organization (muscle and spermatid mitochondrial pathology). Reason: Mutant phenotypes show abnormal mitochondrial morphology and integrity. The broad term is as precise as phenotype-level evidence allows; the mechanistic roles are captured by mitophagy and regulation of mitochondrial fusion/fission rows. Supporting Evidence: PMID:12642658 Mitochondrial pathology is the earliest manifestation of muscle degeneration and a prominent characteristic of individualizing spermatids in parkin mutants |
| GO:0007005 mitochondrion organization | IMP PMID:17123504 The Drosophila parkin homologue is required for normal mitoc... | KEEP AS NON CORE | Summary: IMP mitochondrion organization (spermatid mitochondrial derivatives). Reason: Mutant phenotypes show abnormal mitochondrial morphology and integrity. The broad term is as precise as phenotype-level evidence allows; the mechanistic roles are captured by mitophagy and regulation of mitochondrial fusion/fission rows. Supporting Evidence: PMID:17123504 parkin gene function is necessary for mitochondrial morphogenesis during earlier and later phases of spermiogenesis |
| GO:0007005 mitochondrion organization | IMP PMID:17687034 Drosophila overexpressing parkin R275W mutant exhibits dopam... | KEEP AS NON CORE | Summary: IMP mitochondrion organization (abstract-only). Reason: Mutant phenotypes show abnormal mitochondrial morphology and integrity. The broad term is as precise as phenotype-level evidence allows; the mechanistic roles are captured by mitophagy and regulation of mitochondrial fusion/fission rows. Supporting Evidence: PMID:17687034 these defects caused by the expression of human R275W parkin are highly similar to those triggered by the loss of endogenous parkin in parkin null flies |
| GO:0007005 mitochondrion organization | IMP PMID:18230723 The PINK1/Parkin pathway regulates mitochondrial morphology. | KEEP AS NON CORE | Summary: IMP mitochondrion organization. Reason: Mutant phenotypes show abnormal mitochondrial morphology and integrity. The broad term is as precise as phenotype-level evidence allows; the mechanistic roles are captured by mitophagy and regulation of mitochondrial fusion/fission rows. Supporting Evidence: PMID:18230723 Our studies suggest that the PINK1/Parkin pathway promotes mitochondrial fission and that the loss of mitochondrial and tissue integrity in PINK1 and parkin mutants derives from reduced mitochondrial fission |
| GO:0007005 mitochondrion organization | IMP PMID:18443288 Pink1 regulates mitochondrial dynamics through interaction w... | KEEP AS NON CORE | Summary: IMP mitochondrion organization (Pink1/fission-fusion paper). Reason: Mutant phenotypes show abnormal mitochondrial morphology and integrity. The broad term is as precise as phenotype-level evidence allows; the mechanistic roles are captured by mitophagy and regulation of mitochondrial fusion/fission rows. This full-text paper focuses on Pink1; the parkin row is retained on the curator call. Supporting Evidence: PMID:20194754 Loss of Drosophila PINK1 or parkin causes an increase in Mfn abundance in vivo and concomitant elongation of mitochondria |
| GO:0007005 mitochondrion organization | IMP PMID:24852371 The deubiquitinase USP15 antagonizes Parkin-mediated mitocho... | KEEP AS NON CORE | Summary: IMP mitochondrion organization (parkin RNAi rescued by CG8334 knockdown; abstract-only). Reason: Mutant phenotypes show abnormal mitochondrial morphology and integrity. The broad term is as precise as phenotype-level evidence allows; the mechanistic roles are captured by mitophagy and regulation of mitochondrial fusion/fission rows. Supporting Evidence: PMID:24852371 Knockdown of the DUB CG8334, the closest homolog of USP15 in Drosophila, largely rescues the mitochondrial and behavioral defects of parkin RNAi flies |
| GO:0007005 mitochondrion organization | IMP PMID:29456190 PINK1 Phosphorylates MIC60/Mitofilin to Control Structural P... | KEEP AS NON CORE | Summary: IMP mitochondrion organization (MIC60/cristae paper; abstract-only). Reason: Mutant phenotypes show abnormal mitochondrial morphology and integrity. The broad term is as precise as phenotype-level evidence allows; the mechanistic roles are captured by mitophagy and regulation of mitochondrial fusion/fission rows. The abstract of PMID:29456190 discusses PINK1 only; the full text was not available, so the curator call is deferred to. Supporting Evidence: PMID:12642658 Mitochondrial pathology is the earliest manifestation of muscle degeneration and a prominent characteristic of individualizing spermatids in parkin mutants |
| GO:0007283 spermatogenesis | IMP PMID:17123504 The Drosophila parkin homologue is required for normal mitoc... | KEEP AS NON CORE | Summary: IMP spermatogenesis. Reason: Male sterility from defective spermatid mitochondrial derivatives; a tissue-level consequence of loss of mitochondrial quality control. Supporting Evidence: PMID:17123504 parkin gene function is necessary for mitochondrial morphogenesis during earlier and later phases of spermiogenesis |
| GO:0007283 spermatogenesis | IMP PMID:21383066 The parkin mutant phenotype in the fly is largely rescued by... | KEEP AS NON CORE | Summary: IMP spermatogenesis. Reason: Parkin mutants are male sterile; pleiotropic consequence. Supporting Evidence: PMID:21383066 severe motoric impairment including an inability to fly, female and male sterility, and a decreased life span |
| GO:0008270 zinc ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: IEA zinc ion binding (IBR domain). Reason: RING0, RING1, IBR and RING2 domains of RBR ligases coordinate zinc structurally; true but not the functional activity. Supporting Evidence: file:genes/DROME/park/park-uniprot.txt Belongs to the RBR family. Parkin subfamily. |
| GO:0008344 adult locomotory behavior | IMP PMID:17687034 Drosophila overexpressing parkin R275W mutant exhibits dopam... | KEEP AS NON CORE | Summary: IMP adult locomotory behavior. Reason: Locomotor defects follow muscle and DA neuron degeneration in park mutants. Supporting Evidence: PMID:17687034 these defects caused by the expression of human R275W parkin are highly similar to those triggered by the loss of endogenous parkin in parkin null flies |
| GO:0008344 adult locomotory behavior | IMP PMID:24852371 The deubiquitinase USP15 antagonizes Parkin-mediated mitocho... | KEEP AS NON CORE | Summary: IMP adult locomotory behavior. Reason: Behavioral defects of parkin RNAi flies; downstream phenotype. Supporting Evidence: PMID:24852371 Knockdown of the DUB CG8334, the closest homolog of USP15 in Drosophila, largely rescues the mitochondrial and behavioral defects of parkin RNAi flies |
| GO:0008345 larval locomotory behavior | IMP PMID:27430166 Optimization of wrMTrck to monitor Drosophila larval locomot... | KEEP AS NON CORE | Summary: IMP larval locomotory behavior. Reason: Larval crawling defects in park mutants; downstream phenotype. Supporting Evidence: PMID:27430166 In addition to decreased velocity, loss of parkin alters larval locomotion paths |
| GO:0009896 positive regulation of catabolic process | IEA GO_REF:0000117 | MODIFY | Summary: IEA (ARBA) positive regulation of catabolic process. Reason: True but uninformative; the specific catabolic process parkin promotes is mitophagy (GO:1901526 is a descendant the gene carries). Proposed replacements: positive regulation of mitophagy Supporting Evidence: PMID:20194754 Parkin was also required for CCCP-induced mitophagy in Drosophila cells PMID:23509287 Our findings show that the PINK1-Parkin pathway promotes mitophagy in vivo |
| GO:0010637 negative regulation of mitochondrial fusion | IGI PMID:18799731 The Parkinson's disease genes pink1 and parkin promote mitoc... | ACCEPT | Summary: IGI negative regulation of mitochondrial fusion (with Marf). Reason: Marf knockdown suppresses park phenotypes, and parkin ubiquitinates Marf and lowers its levels, limiting fusion. Supporting Evidence: PMID:18799731 Our data suggest that the pink1/parkin pathway promotes mitochondrial fission and/or inhibits fusion by negatively regulating mfn and opa1 function, and/or positively regulating drp1 PMID:20194754 PINK1 and Parkin mediate the ubiquitination of the profusion factor Mfn on the outer surface of mitochondria |
| GO:0010637 negative regulation of mitochondrial fusion | IMP PMID:20194754 Drosophila parkin requires PINK1 for mitochondrial transloca... | ACCEPT | Summary: IMP negative regulation of mitochondrial fusion. Reason: Loss of parkin raises Marf abundance and elongates mitochondria; parkin ubiquitinates Marf directly. Supporting Evidence: PMID:20194754 Loss of Drosophila PINK1 or parkin causes an increase in Mfn abundance in vivo and concomitant elongation of mitochondria PMID:20194754 PINK1 and Parkin mediate the ubiquitination of the profusion factor Mfn on the outer surface of mitochondria |
| GO:0010821 regulation of mitochondrion organization | IMP PMID:19546216 Loss of parkin or PINK1 function increases Drp1-dependent mi... | KEEP AS NON CORE | Summary: IMP regulation of mitochondrion organization (S2 cell fragmentation on silencing; abstract-only). Reason: The direction of the morphology effect differs between cultured cells (fragmentation on silencing) and adult fly tissues (elongation), so the sign-neutral regulation term is as precise as this evidence allows. Supporting Evidence: PMID:19546216 mitochondrial fragmentation is an early phenomenon upon PINK1/parkin silencing that also occurs in primary mouse neurons and Drosophila S2 cells |
| GO:0016567 protein ubiquitination | IDA PMID:17456438 Drosophila melanogaster Parkin ubiquitinates peanut and sept... | ACCEPT | Summary: IDA protein ubiquitination (septins). Reason: Parkin ubiquitinates substrates directly. Chain type varies by substrate and is not resolved in every assay, so the general term is as precise as these rows allow; mono- and polyubiquitination are captured separately. Supporting Evidence: PMID:17456438 peanut and septin1, D. melanogaster septin proteins, were also ubiquitinated by D. melanogaster Parkin |
| GO:0016567 protein ubiquitination | IEA GO_REF:0000120 | ACCEPT | Summary: IEA protein ubiquitination (InterPro/UniPathway). Reason: Parkin ubiquitinates substrates directly. Chain type varies by substrate and is not resolved in every assay, so the general term is as precise as these rows allow; mono- and polyubiquitination are captured separately. Supporting Evidence: PMID:17456438 D. melanogaster Parkin exhibited UbcH8-dependent E3 ubiquitin-protein ligase activity |
| GO:0016567 protein ubiquitination | IMP PMID:24898855 MUL1 acts in parallel to the PINK1/parkin pathway in regulat... | ACCEPT | Summary: IMP protein ubiquitination (Mfn ubiquitination in S2 cells). Reason: Parkin ubiquitinates substrates directly. Chain type varies by substrate and is not resolved in every assay, so the general term is as precise as these rows allow; mono- and polyubiquitination are captured separately. Supporting Evidence: PMID:24898855 knockdown of both MUL1 and parkin in S2 cells further reduces Mfn ubiquitination below levels seen with knockdown of MUL1 or parkin alone |
| GO:0016567 protein ubiquitination | IMP PMID:24901221 PINK1-mediated phosphorylation of Parkin boosts Parkin activ... | ACCEPT | Summary: IMP protein ubiquitination (phospho-Ser94 regulation). Reason: Parkin ubiquitinates substrates directly. Chain type varies by substrate and is not resolved in every assay, so the general term is as precise as these rows allow; mono- and polyubiquitination are captured separately. Supporting Evidence: PMID:24901221 we have shown that Parkin phosphorylation by PINK1 drives Parkin E3 activity in vivo |
| GO:0022603 regulation of anatomical structure morphogenesis | IEA GO_REF:0000117 | TOO GENERAL | Summary: IEA (ARBA) regulation of anatomical structure morphogenesis. Reason: True but uninformative under GO's current structure: negative regulation of mitochondrial fusion (GO:0010637), ACCEPTed, is_a regulation of mitochondrial fusion (GO:0010635), which is_a regulation of anatomical structure morphogenesis (GO:0022603); this path was confirmed against QuickGO. GO treats the mitochondrion as an anatomical structure here, so the term follows from the mitochondrial row. The specific mitochondrial terms carry the claim. Supporting Evidence: PMID:12642658 Mitochondrial pathology is the earliest manifestation of muscle degeneration and a prominent characteristic of individualizing spermatids in parkin mutants |
| GO:0030382 sperm mitochondrion organization | IMP PMID:12642658 Mitochondrial pathology and apoptotic muscle degeneration in... | KEEP AS NON CORE | Summary: IMP sperm mitochondrion organization. Reason: Spermatid mitochondrial derivatives are abnormal in park mutants; tissue-specific consequence of mitochondrial quality control loss. Supporting Evidence: PMID:12642658 Mitochondrial pathology is the earliest manifestation of muscle degeneration and a prominent characteristic of individualizing spermatids in parkin mutants |
| GO:0030382 sperm mitochondrion organization | IMP PMID:18799731 The Parkinson's disease genes pink1 and parkin promote mitoc... | KEEP AS NON CORE | Summary: IMP sperm mitochondrion organization (abstract-only). Reason: Pink1/parkin genetic interactions with fission/fusion genes in the male germline; curator call deferred to. Supporting Evidence: PMID:17123504 parkin gene function is necessary for mitochondrial morphogenesis during earlier and later phases of spermiogenesis |
| GO:0031624 ubiquitin conjugating enzyme binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA ubiquitin conjugating enzyme binding. Reason: Fly parkin binds the E2 UbcH8 through RING1; E2 binding is a mechanistic step of its ligase activity rather than a separate function. Supporting Evidence: PMID:17456438 D. melanogaster Parkin as an E3 ligase interacts with UbcH8 through its RING1 domain file:genes/DROME/park/park-uniprot.txt They interact with E2 conjugating enzymes and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer |
| GO:0046329 negative regulation of JNK cascade | IDA PMID:16002472 Parkin negatively regulates JNK pathway in the dopaminergic ... | KEEP AS NON CORE | Summary: IDA negative regulation of JNK cascade (abstract-only). Reason: Parkin loss hyperactivates JNK in DA neurons; mechanism is indirect. Supporting Evidence: PMID:16002472 Parkin inhibits the JNK signaling pathway in an E3 activity-dependent manner |
| GO:0046329 negative regulation of JNK cascade | IGI PMID:20496123 Parkin suppresses c-Jun N-terminal kinase-induced cell death... | KEEP AS NON CORE | Summary: IGI negative regulation of JNK cascade (with hep/bsk; abstract-only). Reason: Overexpressed parkin suppresses Hep(CA)/Bsk-induced phenotypes by lowering bsk transcription; indirect and peripheral to the core function. Supporting Evidence: PMID:20496123 Drosophila Parkin suppresses JNK signaling by reducing bsk transcription |
| GO:0046329 negative regulation of JNK cascade | IGI PMID:20496123 Parkin suppresses c-Jun N-terminal kinase-induced cell death... | KEEP AS NON CORE | Summary: IGI negative regulation of JNK cascade (with hep/bsk; abstract-only). Reason: Overexpressed parkin suppresses Hep(CA)/Bsk-induced phenotypes by lowering bsk transcription; indirect and peripheral to the core function. Supporting Evidence: PMID:20496123 Drosophila Parkin suppresses JNK signaling by reducing bsk transcription |
| GO:0048078 positive regulation of compound eye pigmentation | IMP PMID:19692353 Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and... | MARK AS OVER ANNOTATED | Summary: IMP positive regulation of compound eye pigmentation (LRRK2 model; abstract-only). Reason: The paper reports that coexpression of parkin modifies LRRK2-induced eye degeneration in a complex way. This is a modifier effect on a transgenic degeneration model, not evidence that parkin regulates eye pigmentation. Supporting Evidence: PMID:19692353 various indices of the eye and dopaminergic survival were modified in a complex fashion by a concomitant expression of PINK1, DJ-1 or Parkin |
| GO:0048477 oogenesis | IMP PMID:20869429 Diminution of eIF4E activity suppresses parkin mutant phenot... | KEEP AS NON CORE | Summary: IMP oogenesis. Reason: parkin mutant females are sterile; pleiotropic consequence. Supporting Evidence: PMID:20869429 mutant parkin alleles display a broad range of phenotypic alterations, including female infertility |
| GO:0048477 oogenesis | IMP PMID:21383066 The parkin mutant phenotype in the fly is largely rescued by... | KEEP AS NON CORE | Summary: IMP oogenesis. Reason: Female sterility in park mutants; pleiotropic consequence. Supporting Evidence: PMID:21383066 severe motoric impairment including an inability to fly, female and male sterility, and a decreased life span |
| GO:0050804 modulation of chemical synaptic transmission | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA modulation of chemical synaptic transmission. Reason: Fly data show that manipulating parkin phosphorylation alters spontaneous dopamine release from DA neuron terminals, so the IBA has some fly support, but it is peripheral to the mitochondrial quality-control function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000188399 SUPPORTS TRANSFER Parkin-clade node seeded by mammalian PRKN synaptic data; consistent with fly dopamine release data. Supporting Evidence: PMID:24901221 Manipulating the Parkin phosphorylation status affected spontaneous dopamine release in the nerve terminals of dopaminergic neurons |
| GO:0051865 protein autoubiquitination | IDA PMID:17456438 Drosophila melanogaster Parkin ubiquitinates peanut and sept... | KEEP AS NON CORE | Summary: IDA protein autoubiquitination. Reason: Parkin autoubiquitinates in cis; a property of the enzyme used as an activity readout rather than a biological role. Supporting Evidence: PMID:17456438 D. melanogaster Parkin existed in ubiquitinated form in vivo PMID:23770917 parkin autoubiquitinates only in cis |
| GO:0061630 ubiquitin protein ligase activity | EXP PMID:20194754 Drosophila parkin requires PINK1 for mitochondrial transloca... | ACCEPT | Summary: EXP ubiquitin protein ligase activity (Mfn ubiquitination). Reason: Core activity: parkin is an RBR E3 ubiquitin ligase that transfers ubiquitin via a RING2 catalytic cysteine thioester. Supporting Evidence: PMID:20194754 PINK1 and Parkin mediate the ubiquitination of the profusion factor Mfn on the outer surface of mitochondria |
| GO:0061630 ubiquitin protein ligase activity | EXP PMID:23770917 A molecular explanation for the recessive nature of parkin-l... | ACCEPT | Summary: EXP ubiquitin protein ligase activity (fly parkin RING2 structure/activity). Reason: Core activity: parkin is an RBR E3 ubiquitin ligase that transfers ubiquitin via a RING2 catalytic cysteine thioester. Supporting Evidence: PMID:23770917 A single cysteine residue (C449; C431 in human) is exposed on the Ξ²2βΞ²3 loop PMID:23770917 parkin autoubiquitinates only in cis |
| GO:0061630 ubiquitin protein ligase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA ubiquitin protein ligase activity. Reason: Core activity: parkin is an RBR E3 ubiquitin ligase that transfers ubiquitin via a RING2 catalytic cysteine thioester. Supporting Evidence: PMID:17456438 D. melanogaster Parkin exhibited UbcH8-dependent E3 ubiquitin-protein ligase activity file:genes/DROME/park/park-uniprot.txt Belongs to the RBR family. Parkin subfamily. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:17456438 Drosophila melanogaster Parkin ubiquitinates peanut and sept... | ACCEPT | Summary: IDA ubiquitin protein ligase activity. Reason: Core activity: parkin is an RBR E3 ubiquitin ligase that transfers ubiquitin via a RING2 catalytic cysteine thioester. Supporting Evidence: PMID:17456438 D. melanogaster Parkin exhibited UbcH8-dependent E3 ubiquitin-protein ligase activity |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:32138754 PARIS induced defects in mitochondrial biogenesis drive dopa... | ACCEPT | Summary: IDA ubiquitin protein ligase activity (Paris). Reason: Core activity: parkin is an RBR E3 ubiquitin ligase that transfers ubiquitin via a RING2 catalytic cysteine thioester. Supporting Evidence: PMID:32138754 parkin mediated ubiquitination of dPARIS targets it for proteosomal degradation, thereby promoting DA neuron survival in vivo |
| GO:0061630 ubiquitin protein ligase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA ubiquitin protein ligase activity (EC 2.3.2.31). Reason: Core activity: parkin is an RBR E3 ubiquitin ligase that transfers ubiquitin via a RING2 catalytic cysteine thioester. Supporting Evidence: PMID:17456438 D. melanogaster Parkin exhibited UbcH8-dependent E3 ubiquitin-protein ligase activity file:genes/DROME/park/park-uniprot.txt They interact with E2 conjugating enzymes and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer |
| GO:0061630 ubiquitin protein ligase activity | IMP PMID:16002472 Parkin negatively regulates JNK pathway in the dopaminergic ... | ACCEPT | Summary: IMP ubiquitin protein ligase activity (E3-dependent JNK inhibition; abstract-only). Reason: Core activity: parkin is an RBR E3 ubiquitin ligase that transfers ubiquitin via a RING2 catalytic cysteine thioester. Supporting Evidence: PMID:16002472 Parkin inhibits the JNK signaling pathway in an E3 activity-dependent manner |
| GO:0061630 ubiquitin protein ligase activity | IMP PMID:24901221 PINK1-mediated phosphorylation of Parkin boosts Parkin activ... | ACCEPT | Summary: IMP ubiquitin protein ligase activity (phospho-Ser94 boosts E3 activity). Reason: Core activity: parkin is an RBR E3 ubiquitin ligase that transfers ubiquitin via a RING2 catalytic cysteine thioester. Supporting Evidence: PMID:24901221 we have shown that Parkin phosphorylation by PINK1 drives Parkin E3 activity in vivo |
| GO:0061734 type 2 mitophagy | IMP PMID:20194754 Drosophila parkin requires PINK1 for mitochondrial transloca... | ACCEPT | Summary: IMP type 2 mitophagy (CCCP-induced, PINK1-dependent). Reason: Core process: in S2 cells, depolarization recruits parkin to mitochondria in a PINK1-dependent way and parkin is required for the ensuing mitophagy, matching the type 2 mitophagy definition. Supporting Evidence: PMID:20194754 Parkin was also required for CCCP-induced mitophagy in Drosophila cells PMID:20194754 a large proportion of cells showed Parkin-GFP accumulated at or near mitochondria |
| GO:0061734 type 2 mitophagy | IMP PMID:24192653 Mitochondrial contagion induced by Parkin deficiency in Dros... | ACCEPT | Summary: IMP type 2 mitophagy (cardiomyocytes). Reason: Parkin-deficient cardiomyocyte mitochondria are depolarized and their mitophagic culling is impaired. Supporting Evidence: PMID:24192653 Parkin deficiency and resulting mitophagic disruption produces cardiomyopathy |
| GO:0070050 neuron cellular homeostasis | IMP PMID:17687034 Drosophila overexpressing parkin R275W mutant exhibits dopam... | KEEP AS NON CORE | Summary: IMP neuron cellular homeostasis (abstract-only). Reason: DA neuron degeneration in parkin loss/R275W models; downstream consequence. Supporting Evidence: PMID:17687034 these defects caused by the expression of human R275W parkin are highly similar to those triggered by the loss of endogenous parkin in parkin null flies |
| GO:0090141 positive regulation of mitochondrial fission | IMP PMID:18799731 The Parkinson's disease genes pink1 and parkin promote mitoc... | KEEP AS NON CORE | Summary: IMP positive regulation of mitochondrial fission. Reason: Genetic interactions place the pathway as promoting fission and/or inhibiting fusion; parkin is not part of the fission machinery and acts mainly through Marf turnover. Supporting Evidence: PMID:18799731 Our data suggest that the pink1/parkin pathway promotes mitochondrial fission and/or inhibits fusion by negatively regulating mfn and opa1 function, and/or positively regulating drp1 PMID:18799731 These results suggest that pink1 and parkin are likely not core components of the drp1-mediated mitochondrial fission machinery |
| GO:0090141 positive regulation of mitochondrial fission | IMP PMID:20194754 Drosophila parkin requires PINK1 for mitochondrial transloca... | KEEP AS NON CORE | Summary: IMP positive regulation of mitochondrial fission. Reason: Loss of parkin elongates mitochondria through Marf accumulation; the net effect favours fission. Supporting Evidence: PMID:20194754 Loss of Drosophila PINK1 or parkin causes an increase in Mfn abundance in vivo and concomitant elongation of mitochondria |
| GO:1900407 regulation of cellular response to oxidative stress | IDA PMID:20483372 Extended lifespan of Drosophila parkin mutants through seque... | KEEP AS NON CORE | Summary: IDA regulation of cellular response to oxidative stress (abstract-only). Reason: Parkin protects against redox-active metals and pesticides; the effect is indirect, probably through mitochondrial quality control. Supporting Evidence: PMID:20483372 our results demonstrate an important function of parkin in the protection against redox-active metals and pesticides |
| GO:1901526 positive regulation of mitophagy | IMP PMID:28435104 Drosophila PINK1 and parkin loss-of-function mutants display... | ACCEPT | Summary: IMP positive regulation of mitophagy citing a behaviour/circadian paper. Reason: The claim is true for parkin: PINK1-activated parkin ubiquitinates outer membrane proteins that signal mitophagy. However, the cited paper (full text read) assays memory, circadian rhythms and clock-neuron electrophysiology only and does not measure mitophagy; the reference appears wrong. Supporting Evidence: PMID:23509287 Our findings show that the PINK1-Parkin pathway promotes mitophagy in vivo PMID:20194754 Parkin was also required for CCCP-induced mitophagy in Drosophila cells |
| GO:1902532 negative regulation of intracellular signal transduction | IEA GO_REF:0000117 | MODIFY | Summary: IEA (ARBA) negative regulation of intracellular signal transduction. Reason: True but general; the specific pathway with fly evidence is the JNK cascade (GO:0046329 is a descendant the gene carries). Proposed replacements: negative regulation of JNK cascade Supporting Evidence: PMID:16002472 Parkin inhibits the JNK signaling pathway in an E3 activity-dependent manner PMID:20496123 Drosophila Parkin suppresses JNK signaling by reducing bsk transcription |
| GO:1903599 positive regulation of autophagy of mitochondrion | IGI PMID:27906179 PINK1-dependent phosphorylation of PINK1 and Parkin is essen... | MODIFY | Summary: IGI positive regulation of autophagy of mitochondrion (with Pink1). Reason: Correct but general: the process parkin promotes in flies is macroautophagic mitophagy (Atg7-dependent), captured by the descendant GO:1901526 positive regulation of mitophagy, which the gene carries. Proposed replacements: positive regulation of mitophagy Supporting Evidence: PMID:27906179 phosphorylation of Parkin by PINK1 is dispensable for its translocation but required for its activation |
| GO:1903599 positive regulation of autophagy of mitochondrion | IMP PMID:23509287 The PINK1-Parkin pathway promotes both mitophagy and selecti... | MODIFY | Summary: IMP positive regulation of autophagy of mitochondrion (in vivo turnover). Reason: Correct but general: the process parkin promotes in flies is macroautophagic mitophagy (Atg7-dependent), captured by the descendant GO:1901526 positive regulation of mitophagy, which the gene carries. Proposed replacements: positive regulation of mitophagy Supporting Evidence: PMID:23509287 parkin null mutants showed a significant overall slowing of mitochondrial protein turnover PMID:23509287 Our findings show that the PINK1-Parkin pathway promotes mitophagy in vivo |
| GO:1904061 positive regulation of locomotor rhythm | IMP PMID:28435104 Drosophila PINK1 and parkin loss-of-function mutants display... | MARK AS OVER ANNOTATED | Summary: IMP positive regulation of locomotor rhythm. Reason: park25 flies show weakened circadian rhythms, a downstream consequence of neuronal dysfunction; parkin is not a regulator of the circadian clock. Supporting Evidence: PMID:28435104 the parkin null flies tended to show more of a weakening of rhythms, along with an overall increase in activity |
| GO:1904457 positive regulation of neuronal action potential | IMP PMID:28435104 Drosophila PINK1 and parkin loss-of-function mutants display... | MARK AS OVER ANNOTATED | Summary: IMP positive regulation of neuronal action potential. Reason: park25 clock neurons lose their day/night firing difference; an indirect electrophysiological phenotype, not evidence that parkin regulates action potentials. Supporting Evidence: PMID:28435104 PINK1B9 neurons have a higher firing rate and park25 neurons do not show a day/night difference |
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Download this section (compressed HTML)Q: Is parkin required for basal mitophagy in fly neurons and muscle in vivo, or mainly for stress-induced (depolarization-triggered) mitophagy, given that basal mitophagy reporters show modest parkin dependence?
Q: Which outer membrane substrates (Marf, Porin, Miro, Tom20) carry which chain types in vivo, and how does parkin choose mono- versus polyubiquitination of Porin?
Q: FlyBase IMP GO:1901526 is attributed to PMID:28435104, which does not assay mitophagy; should the row be re-referenced?
Experiment: Quantify mitophagy with mt-Keima or mito-QC reporters in park null flies rescued with wild-type, C449S, S94A and T433N parkin, in flight muscle and DA neurons, to separate catalytic, activation and Porin-monoubiquitination requirements in vivo.
Experiment: Ubiquitin-remnant (diGly) proteomics of mitochondria from wild-type and park mutant flies after depolarization, to define the endogenous substrate set and linkage types.
parkin (park) encodes an E3 ubiquitin ligase with a key role in protein ubiquitination. It is involved in mitochondrion organization, oxidative stress and locomotion.
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