PDR-1 is the C. elegans ortholog of human Parkin, an RBR-family E3 ubiquitin-protein ligase that functions in the conserved PINK-1/PDR-1 mitophagy pathway. The protein contains an N-terminal ubiquitin-like (Ubl) domain and C-terminal RING0-RING1-IBR-RING2 domains characteristic of RBR E3 ligases. By analogy with mammalian Parkin, PDR-1 is expected to be activated by PINK-1-mediated phosphorylation and to translocate to damaged mitochondria, where it ubiquitinates outer mitochondrial membrane proteins to target them for mitophagic degradation. In C. elegans, PDR-1 and PINK-1 are required for stress-induced mitophagy, for example after frataxin depletion, and they shape the tissue distribution of a deleterious mitochondrial genome. PDR-1 is primarily cytosolic but shows enriched association with autophagy-lysosomal compartments and is recruited to the mitochondrial outer membrane during mitophagy. Beyond mitophagy, PDR-1 also ubiquitinates CED-10/Rac1 to regulate apoptotic cell engulfment and cell migration. Loss of pdr-1 impairs mitochondrial quality control, increases sensitivity to mitochondrial complex I inhibitors, and affects lifespan and proteostasis in models of neurodegeneration.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: PDR-1 is primarily cytosolic/cytoplasmic as demonstrated by multiple studies. The mCherry::PDR-1 reporter showed predominantly cytosolic distribution with enrichment in lysosomal-like compartments (Vozdek et al. 2023, pdr-1-deep-research-falcon.md). Reason: Cytoplasmic localization is well-supported by experimental evidence and phylogenetic inference. This represents a core localization for PDR-1. Supporting Evidence: file:worm/pdr-1/pdr-1-deep-research-falcon.md Reporter and biochemical data place PDR-1 primarily in the cytosol with enriched compartmentalization to autophagy-lysosomal structures |
| GO:0031624 ubiquitin conjugating enzyme binding | IBA GO_REF:0000033 | ACCEPT | Summary: PDR-1 physically associates with E2 ubiquitin conjugating enzymes as part of its E3 ligase function. PMID:16204351 states that PDR-1 cooperates with a conserved degradation machinery to mediate ubiquitin conjugation. Reason: Essential for E3 ubiquitin ligase function; PDR-1 cooperates with E2 enzymes to mediate ubiquitin conjugation. Well-supported by experimental and phylogenetic evidence. Supporting Evidence: PMID:16204351 PDR-1 protein physically associates and cooperates with a conserved degradation machinery to mediate ubiquitin conjugation |
| GO:0050804 modulation of chemical synaptic transmission | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: This annotation is inferred from mammalian Parkin orthologs where synaptic function has been studied more extensively. While pdr-1 is expressed in neurons and loss causes proteotoxic stress sensitivity, direct evidence for synaptic transmission modulation in C. elegans is limited. Reason: The annotation is phylogenetically reasonable based on mammalian Parkin studies, but represents a downstream consequence rather than a core molecular function of PDR-1. The core function is E3 ligase activity in mitophagy. |
| GO:0000423 mitophagy | IBA GO_REF:0000033 | ACCEPT | Summary: Mitophagy is a core function of PDR-1 in the conserved PINK-1/PDR-1 pathway. This is strongly supported by IMP evidence from PMID:25896323 and PMID:26469957, as well as recent studies showing PDR-1 coordinates with DCT-1 in mitophagic clearance (Vozdek et al. 2023, Markaki et al. 2021). Reason: This represents a core biological process function of PDR-1. The PINK-1/PDR-1 mitophagy pathway is highly conserved and well-characterized in C. elegans. Supporting Evidence: PMID:25896323 We find that DCT-1 is a key mediator of mitophagy and longevity assurance under conditions of stress in C. elegans |
| GO:0006511 ubiquitin-dependent protein catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: PDR-1 ubiquitinates target proteins for proteasomal degradation. IMP evidence from PMID:24625979 demonstrated that PDR-1 ubiquitinates CED-10 for proteasomal degradation via K48 ubiquitin linkages. Reason: Core function as an E3 ubiquitin ligase that targets proteins for degradation. Well-supported by experimental evidence showing K48-linked ubiquitination of substrates. Supporting Evidence: PMID:24625979 No CED-10 immunostaining was observed when ubiquitin-K48R was used in pull-down assays, indicating that PDR-1 ubiquitylated CED-10 through K48 ubiquitin linkages |
| GO:0061630 ubiquitin protein ligase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PDR-1 is an RBR-family E3 ubiquitin protein ligase. This is the core molecular function supported by domain architecture and experimental evidence including IDA from PMID:16204351 and IMP from PMID:24625979. Reason: Core molecular function of PDR-1. The protein contains RBR domains characteristic of E3 ubiquitin ligases and demonstrates ubiquitin ligase activity in vitro and in vivo. Supporting Evidence: PMID:16204351 PDR-1 protein physically associates and cooperates with a conserved degradation machinery to mediate ubiquitin conjugation |
| GO:0000151 ubiquitin ligase complex | IBA GO_REF:0000033 | ACCEPT | Summary: PDR-1 forms an E3 ubiquitin ligase complex with E2 enzymes. IPI evidence from PMID:16204351 showed PDR-1 cooperates with conserved degradation machinery. Reason: Core complex membership for E3 ligase function. Supported by experimental protein-protein interaction data. Supporting Evidence: PMID:16204351 PDR-1 protein physically associates and cooperates with a conserved degradation machinery to mediate ubiquitin conjugation |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA annotation from PANTHER node PTN000188399 (mammalian PRKN in Homo sapiens O60260 and Rattus norvegicus RGD:61797). While pdr-1 mutants show sensitivity to tunicamycin-induced ER stress (PMID:16204351), C. elegans PDR-1 localizes to the cytosol and is recruited to the mitochondrial outer membrane during mitophagy (PMID:25896323), with no evidence of ER residence or activity at the ER in worms. Reason: Examined as a synthesis row on a root organelle term (ORGANELLES policy). This IBA propagates GO:0005783 (endoplasmic reticulum) from PANTHER Parkin-clade node PTN000188399 (mammalian PRKN in human O60260 and rat RGD:61797) across Bilateria to C. elegans PDR-1. In C. elegans, PDR-1 is a cytosolic E3 ubiquitin ligase that translocates to the mitochondrial outer membrane (GO:0005741, IDA from PMID:25896323) to mediate mitophagy, and no study demonstrates ER localization of endogenous or reporter PDR-1 in worms (just as in invertebrate ortholog DROME/park). Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000188399 SUPPORTS SOURCE BUT NOT TARGET Parkin-clade node propagating mammalian PRKN (human O60260, rat RGD:61797) endoplasmic reticulum localization to invertebrate orthologs (C. elegans pdr-1, D. melanogaster park) where the protein is cytosolic and mitochondrial. Supporting Evidence: file:worm/pdr-1/pdr-1-deep-research-falcon.md Reporter and biochemical data place PDR-1 primarily in the cytosol with enriched compartmentalization to autophagy-lysosomal structures |
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA annotation from PANTHER node PTN000188399 (mammalian PRKN in Homo sapiens O60260 and Rattus norvegicus RGD:61797). No experimental evidence supports Golgi apparatus localization for C. elegans PDR-1, which is cytosolic and recruited to the mitochondrial outer membrane during mitophagy. Reason: Examined as a synthesis row on a root organelle term (ORGANELLES policy). This IBA propagates GO:0005794 (Golgi apparatus) from PANTHER Parkin-clade node PTN000188399 (mammalian PRKN in human O60260 and rat RGD:61797) across Bilateria to C. elegans PDR-1. In C. elegans, PDR-1 resides in the cytosol and is recruited to the mitochondrial outer membrane during mitophagy (PMID:25896323), with no evidence for Golgi localization (harmonized with invertebrate ortholog DROME/park). Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000188399 SUPPORTS SOURCE BUT NOT TARGET Parkin-clade node propagating mammalian PRKN (human O60260, rat RGD:61797) Golgi apparatus localization to invertebrate orthologs (C. elegans pdr-1, D. melanogaster park) where the protein is cytosolic and mitochondrial. Supporting Evidence: file:worm/pdr-1/pdr-1-deep-research-falcon.md Reporter and biochemical data place PDR-1 primarily in the cytosol with enriched compartmentalization to autophagy-lysosomal structures |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: PDR-1 is primarily cytosolic, consistent with the mCherry::PDR-1 reporter showing predominantly cytosolic distribution (Vozdek et al. 2023). Reason: Core subcellular localization. PDR-1 is primarily cytosolic with dynamic recruitment to mitochondria during mitophagy. Supporting Evidence: file:worm/pdr-1/pdr-1-deep-research-falcon.md Reporter and biochemical data place PDR-1 primarily in the cytosol with enriched compartmentalization to autophagy-lysosomal structures |
| GO:0000151 ubiquitin ligase complex | IEA GO_REF:0000104 | ACCEPT | Summary: Electronic annotation based on sequence features. Consistent with IBA and IPI annotations for the same term. Reason: Correct annotation consistent with experimental evidence. Electronic inference is valid given RBR domain architecture. |
| GO:0004842 ubiquitin-protein transferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation based on InterPro domain IPR003977 (Parkin) and IPR031127 (E3_UB_ligase_RBR). Consistent with IDA and IMP evidence. Reason: Core molecular function. Domain-based electronic inference is validated by experimental evidence showing ubiquitin transferase activity. |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | MODIFY | Summary: PDR-1 is recruited to mitochondria during mitophagy. More specific localization to mitochondrial outer membrane is supported by the deep research review. Reason: While correct that PDR-1 localizes to mitochondria, the more specific term GO:0005741 (mitochondrial outer membrane) is better supported by experimental evidence. Proposed replacements: mitochondrial outer membrane |
| GO:0005829 cytosol | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation consistent with IBA annotation and experimental evidence. Reason: Duplicate of IBA annotation. Cytosolic localization is well-supported. |
| GO:0006914 autophagy | IEA GO_REF:0000120 | MODIFY | Summary: PDR-1 functions in autophagy, specifically mitophagy. The more specific term mitophagy (GO:0000423) is more appropriate for this protein. Reason: While autophagy is technically correct, mitophagy is the more specific and accurate process for PDR-1 function. Proposed replacements: mitophagy |
| GO:0008270 zinc ion binding | IEA GO_REF:0000120 | ACCEPT | Summary: PDR-1 contains RING finger zinc-binding domains (Parkin_Znf-RING, IPR041565) that are essential for E3 ligase catalytic activity. Reason: Structurally supported by presence of zinc-finger RING domains. Required for E3 ligase function. |
| GO:0009893 positive regulation of metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA machine learning annotation. This is a very general term that does not capture the specific function of PDR-1. The protein functions in ubiquitin-dependent protein catabolism and mitophagy. Reason: Overly broad annotation from machine learning. Does not provide useful functional information about PDR-1's specific role in ubiquitination and mitophagy. |
| GO:0016567 protein ubiquitination | IEA GO_REF:0000120 | ACCEPT | Summary: Core function of PDR-1 as an E3 ubiquitin ligase. Consistent with IMP evidence from PMID:16239214 and PMID:24625979. Reason: Core biological process function. PDR-1 catalyzes protein ubiquitination as its primary enzymatic activity. |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: Correct but overly general. PDR-1 has more specific ubiquitin-protein transferase activity (GO:0004842). Reason: Too general. More specific terms like ubiquitin-protein transferase activity or ubiquitin protein ligase activity are more informative. |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | MODIFY | Summary: Correct but overly general. PDR-1 binds zinc ions specifically through its RING finger domains. Reason: The more specific term zinc ion binding (GO:0008270) is more accurate and already annotated. Proposed replacements: zinc ion binding |
| GO:0061630 ubiquitin protein ligase activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC-based annotation for E3 ubiquitin ligase activity (EC 2.3.2.31). Consistent with IBA annotation and experimental evidence. Reason: Core molecular function. EC classification matches the enzymatic activity of PDR-1. |
| GO:0000423 mitophagy | IMP PMID:26469957 A bacterial metabolite induces glutathione-tractable proteos... | ACCEPT | Summary: Martinez et al. 2015 demonstrated that a bacterial metabolite induces PINK-1-dependent autophagy/mitophagy in C. elegans. The study showed that pdr-1 functions with pink-1 in this pathway, and GSH can compensate for combined loss of pink-1 and pdr-1. Reason: Core function with direct experimental evidence. The study demonstrated PDR-1 involvement in mitophagy through genetic analysis. Supporting Evidence: file:worm/pdr-1/pdr-1-deep-research-falcon.md PDR-1 acts downstream of PINK-1 in canonical mitophagy, cooperating with receptors such as DCT-1 to ubiquitinate OMM substrates PMID:26469957 A bacterial metabolite induces glutathione-tractable proteostatic damage, proteasomal disturbances, and PINK1-dependent autophagy in C. |
| GO:0000423 mitophagy | IMP PMID:25896323 Coordination of mitophagy and mitochondrial biogenesis durin... | ACCEPT | Summary: Palikaras et al. 2015 (Nature) characterized the coordination of mitophagy and mitochondrial biogenesis during aging in C. elegans. PDR-1 functions with PINK-1 and DCT-1 in the mitophagy pathway. Reason: High-quality experimental evidence from Nature demonstrating PDR-1 function in mitophagy pathway. Core function. Supporting Evidence: PMID:25896323 We find that DCT-1 is a key mediator of mitophagy and longevity assurance under conditions of stress in C. elegans |
| GO:0030336 negative regulation of cell migration | IGI PMID:24625979 PDR-1/hParkin negatively regulates the phagocytosis of apopt... | KEEP AS NON CORE | Summary: Cabello et al. 2014 demonstrated that PDR-1 negatively regulates distal tip cell (DTC) migration by ubiquitinating CED-10/Rac1. Loss of pdr-1 suppressed DTC migration defects in ced-10 mutants. Reason: Well-supported by experimental evidence but represents a secondary function through regulation of CED-10. Not the primary function of PDR-1. Supporting Evidence: PMID:24625979 However, mutations of pdr-1 decreased the percentage of gonadal morphology defects in the two ced-10 alleles tested |
| GO:0004842 ubiquitin-protein transferase activity | IMP PMID:24625979 PDR-1/hParkin negatively regulates the phagocytosis of apopt... | ACCEPT | Summary: Cabello et al. 2014 demonstrated that PDR-1 has ubiquitin-protein transferase activity, specifically ubiquitinating CED-10 through K48 linkages for proteasomal degradation. Reason: Core molecular function with direct biochemical evidence. The study showed PDR-1 ubiquitinates CED-10 through K48 linkages. Supporting Evidence: PMID:24625979 As expected, the E3 ligase-null mutant of PDR-1 (lg103) failed to induce CED-10 ubiquitylation in the presence of MG-132 in comparison with the non-mutated PDR-1 |
| GO:0005741 mitochondrial outer membrane | IDA PMID:25896323 Coordination of mitophagy and mitochondrial biogenesis durin... | ACCEPT | Summary: Palikaras et al. 2015 characterized mitophagy in C. elegans. PDR-1 is recruited to mitochondria during mitophagy, consistent with its role in ubiquitinating OMM proteins for mitophagic degradation. Reason: Direct experimental evidence for localization. This is the site where PDR-1 acts to ubiquitinate mitochondrial proteins during mitophagy. Supporting Evidence: PMID:25896323 mitophagy, a selective type of autophagy targeting mitochondria for degradation, interfaces with mitochondrial biogenesis to regulate mitochondrial content and longevity |
| GO:0006511 ubiquitin-dependent protein catabolic process | IMP PMID:24625979 PDR-1/hParkin negatively regulates the phagocytosis of apopt... | ACCEPT | Summary: Cabello et al. 2014 showed that PDR-1 targets CED-10 for ubiquitin-dependent proteasomal degradation through K48 ubiquitin linkages. Reason: Core function with biochemical evidence. PDR-1 ubiquitinates substrates for proteasomal degradation. Supporting Evidence: PMID:24625979 The amount of CED-10 is increased in the absence of PDR-1 |
| GO:1901075 negative regulation of engulfment of apoptotic cell | IMP PMID:24625979 PDR-1/hParkin negatively regulates the phagocytosis of apopt... | KEEP AS NON CORE | Summary: Cabello et al. 2014 demonstrated that PDR-1 negatively regulates apoptotic cell engulfment by ubiquitinating CED-10/Rac1. Loss of pdr-1 accelerates engulfment and reduces unengulfed cell corpses. Reason: Well-supported experimental evidence but represents a secondary function through CED-10 regulation. The primary function of PDR-1 is in mitophagy, not developmental cell death clearance. Supporting Evidence: PMID:24625979 Our genetic and biochemical studies indicate that PDR-1 inhibits apoptotic cell engulfment and DTC migration by ubiquitylating CED-10 for degradation |
| GO:0000151 ubiquitin ligase complex | IPI PMID:16204351 A Caenorhabditis elegans Parkin mutant with altered solubili... | ACCEPT | Summary: Springer et al. 2005 demonstrated that PDR-1 physically interacts with ubiquitin conjugating enzymes to form E3 ligase complexes. Reason: Direct protein-protein interaction evidence. PDR-1 forms complexes with E2 enzymes for ubiquitin conjugation. Supporting Evidence: PMID:16204351 PDR-1 protein physically associates and cooperates with a conserved degradation machinery to mediate ubiquitin conjugation |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:16204351 A Caenorhabditis elegans Parkin mutant with altered solubili... | ACCEPT | Summary: Springer et al. 2005 characterized PDR-1 as an E3 ubiquitin ligase. The paper showed that PDR-1 has ubiquitin-protein transferase activity including autoubiquitination. Reason: Core molecular function with direct assay evidence. Supporting Evidence: PMID:16204351 the corresponding truncated protein PDR-1(Deltaaa24-247) aggregates in cell culture, but still interacts with its ubiquitylation co-enzymes |
| GO:0005737 cytoplasm | IDA PMID:16204351 A Caenorhabditis elegans Parkin mutant with altered solubili... | ACCEPT | Summary: Springer et al. 2005 demonstrated cytoplasmic localization of PDR-1. The paper noted altered solubility and intracellular localization in mutants. Reason: Direct experimental evidence for cytoplasmic localization. Supporting Evidence: PMID:16204351 an in-frame deletion variant with altered solubility and intracellular localization properties is hypersensitive toward different proteotoxic stress conditions |
| GO:0031624 ubiquitin conjugating enzyme binding | IPI PMID:16204351 A Caenorhabditis elegans Parkin mutant with altered solubili... | ACCEPT | Summary: Springer et al. 2005 demonstrated physical interaction between PDR-1 and ubiquitin conjugating enzymes. Reason: Core molecular function for E3 ligase activity. Direct protein-protein interaction evidence. Supporting Evidence: PMID:16204351 the corresponding truncated protein PDR-1(Deltaaa24-247) aggregates in cell culture, but still interacts with its ubiquitylation co-enzymes |
| GO:0043025 neuronal cell body | IDA PMID:16204351 A Caenorhabditis elegans Parkin mutant with altered solubili... | ACCEPT | Summary: Springer et al. 2005 studied PDR-1 in the context of neurodegeneration models. PDR-1 is relevant to neuronal function based on the proteotoxic stress studies. Reason: Direct experimental evidence for neuronal localization, relevant to the protein's role in neuroprotection. Supporting Evidence: PMID:16204351 Both endoplasmic reticulum-derived folding stress and cytosolic stress conferred by expression of mutant human alpha-synuclein resulted in severe developmental defects and lethality |
| GO:0051865 protein autoubiquitination | IDA PMID:16204351 A Caenorhabditis elegans Parkin mutant with altered solubili... | ACCEPT | Summary: Springer et al. 2005 demonstrated that PDR-1 interacts with ubiquitylation co-enzymes, characteristic of RBR E3 ligases that perform autoubiquitination. Reason: Direct experimental evidence for autoubiquitination activity. Characteristic of RBR family E3 ligases. Supporting Evidence: PMID:16204351 the corresponding truncated protein PDR-1(Deltaaa24-247) aggregates in cell culture, but still interacts with its ubiquitylation co-enzymes |
| GO:0008340 determination of adult lifespan | IMP PMID:16239214 Similar patterns of mitochondrial vulnerability and rescue i... | KEEP AS NON CORE | Summary: Ved et al. 2005 demonstrated that pdr-1 affects adult lifespan in the context of mitochondrial vulnerability and stress responses. This is a downstream consequence of mitochondrial quality control function. Reason: Experimental evidence supports lifespan effects, but this is a pleiotropic consequence of mitochondrial quality control rather than a core function. PDR-1's primary role is in mitophagy. Supporting Evidence: PMID:16239214 expressing alpha-synuclein, deleting parkin (K08E3.7), or knocking down DJ-1 (B0432.2) or parkin produces similar patterns of pharmacological vulnerability and rescue |
| GO:0009636 response to toxic substance | IMP PMID:16239214 Similar patterns of mitochondrial vulnerability and rescue i... | KEEP AS NON CORE | Summary: Ved et al. 2005 showed that pdr-1 deletion increases sensitivity to mitochondrial complex I inhibitors (rotenone, fenperoximate, pyridaben, stigmatellin) but not to paraquat or sodium azide. Reason: Experimental evidence supports role in toxin response, but this is a consequence of mitochondrial quality control function rather than a primary function. Vulnerability to complex I inhibitors reflects mitochondrial dysfunction. Supporting Evidence: PMID:16239214 C. elegans lines with these genetic changes were more vulnerable than nontransgenic nematodes to mitochondrial complex I inhibitors, including rotenone, fenperoximate, pyridaben, or stigmatellin |
| GO:0016567 protein ubiquitination | IMP PMID:16239214 Similar patterns of mitochondrial vulnerability and rescue i... | ACCEPT | Summary: Ved et al. 2005 implicated pdr-1 in protein ubiquitination through genetic analysis of mitochondrial vulnerability patterns. Reason: Core molecular function of PDR-1 as an E3 ubiquitin ligase. Supporting Evidence: PMID:16239214 expressing alpha-synuclein, deleting parkin (K08E3.7), or knocking down DJ-1 (B0432.2) or parkin produces similar patterns of pharmacological vulnerability and rescue |
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Download this section (compressed HTML)Q: What are the specific mitochondrial outer membrane substrates of PDR-1 in C. elegans?
Q: How does PDR-1 activity change during aging and in response to different stressors?
Q: What is the relative contribution of mitophagy versus CED-10 regulation to PDR-1 function in different tissues?
Experiment: Mass spectrometry identification of PDR-1 substrates at the mitochondrial outer membrane
Hypothesis: PDR-1 ubiquitinates specific OMM proteins analogous to mammalian Parkin substrates
Experiment: Time-lapse imaging of PDR-1 recruitment to damaged mitochondria using the mCherry::PDR-1 reporter
Hypothesis: PDR-1 is dynamically recruited to depolarized mitochondria in a PINK-1 dependent manner
Experiment: Tissue-specific rescue experiments to determine where PDR-1 function is most critical for lifespan and stress resistance
Hypothesis: Neuronal PDR-1 expression is sufficient to rescue lifespan and stress resistance phenotypes
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Download this section (compressed HTML)pdr-1 encodes an ortholog of human parkin (PARK2).
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