pdr-1

Existing Annotations Review

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	UNDECIDED	Summary: This annotation is inferred from mammalian Parkin localization to ER. While pdr-1 mutants show sensitivity to ER-derived folding stress (PMID:16204351), direct ER localization of PDR-1 in C. elegans has not been demonstrated. Reason: Phylogenetic inference from mammalian orthologs, but direct experimental evidence for ER localization in C. elegans is lacking. The primary localization is cytoplasm with recruitment to mitochondria.
GO:0005794 Golgi apparatus	IBA GO_REF:0000033	UNDECIDED	Summary: This annotation is inferred from mammalian Parkin studies. No direct evidence for Golgi localization in C. elegans has been reported. The primary localization is cytoplasm with recruitment to mitochondria during mitophagy. Reason: Phylogenetic inference only. No direct experimental evidence for Golgi localization in C. elegans. May represent over-annotation from mammalian studies.
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

Gene Description

Existing Annotations Review

Core Functions

PDR-1 is an RBR-family E3 ubiquitin-protein ligase that catalyzes the transfer of ubiquitin to substrate proteins. It contains the characteristic Ubl-RING0-RING1-IBR-RING2 domain architecture and is activated by PINK-1-mediated phosphorylation.

PDR-1 transfers ubiquitin to target proteins including CED-10/Rac1 and mitochondrial outer membrane proteins. The protein catalyzes K48-linked ubiquitination for proteasomal degradation and also performs autoubiquitination.

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