PDE6D (PDEdelta, PrBP/delta) is a small (~17 kDa), ubiquitously expressed cytosolic prenyl-binding protein with an immunoglobulin-like beta-sandwich fold related to RhoGDI. Its deep hydrophobic pocket binds the farnesyl (and some geranylgeranyl) moiety of C-terminally prenylated proteins and solubilizes them from membranes. In this way it acts as a GDI-like carrier that lets lipidated cargo diffuse through the cytoplasm. Cargo is unloaded when the Arf-like GTPases ARL2 or ARL3 bind PDE6D in their GTP-bound state and allosterically eject the prenyl group. Two roles follow from this mechanism. In cilia, PDE6D delivers farnesylated cargo such as INPP5E and, in photoreceptors, GRK1 and PDE6 catalytic subunits; ciliary ARL3-GTP (activated by ARL13B) releases the cargo into the ciliary membrane, and the RCC1-like domain of RPGR can recruit cargo-loaded PDE6D near the transition zone. Outside cilia, PDE6D solubilizes farnesylated Ras-family proteins (KRAS, HRAS, RHEB, Rap1), and ARL2-mediated release on perinuclear membranes keeps them enriched at the plasma membrane and supports Ras signalling; small molecules that occupy the prenyl pocket displace KRAS. PDE6D was first described as a delta subunit that detaches PDE6 from rod outer segment membranes. A homozygous PDE6D splice mutation causes Joubert syndrome, and Pde6d-null mice develop a slowly progressing rod/cone dystrophy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001750 photoreceptor outer segment | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Photoreceptor outer segment, by Ensembl Compara transfer from mouse. Reason: PDE6D is abundant in photoreceptors and carries prenylated phototransduction proteins toward the outer segment. As a soluble carrier it is not specific to this compartment. |
| GO:0001750 photoreceptor outer segment | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Photoreceptor outer segment, by similarity to mouse. Reason: As for the IEA row. |
| GO:0001917 photoreceptor inner segment | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Photoreceptor inner segment, by Ensembl Compara transfer from mouse. Reason: Consistent with a cytosolic carrier in the photoreceptor inner segment; non-core. |
| GO:0001917 photoreceptor inner segment | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Photoreceptor inner segment, by similarity to mouse. Reason: As for the IEA row. |
| GO:0005095 GTPase inhibitor activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: GTPase inhibitor activity, by Ensembl Compara transfer from mouse. Reason: Binding of PDE6D to GTP-bound ARL2/ARL3 stabilizes the GTP state, and PDE6D has been described as a GDI-like factor. This is a consequence of effector binding, not the evolved function of PDE6D, which is to carry prenylated cargo. Kept, but non-core. Supporting Evidence: PMID:22002721 We thus describe a new transport system for farnesylated G proteins involving a GDI-like molecule and an unequivocal GDF. |
| GO:0005095 GTPase inhibitor activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: GTPase inhibitor activity, by similarity to mouse. Reason: As for the IEA row. |
| GO:0005515 protein binding | IPI PMID:11980706 The complex of Arl2-GTP and PDE delta: from structure to fun... | MODIFY | Summary: Protein binding with HRAS. Reason: HRAS is a farnesylated Ras-family cargo held in the PDE6D prenyl-binding pocket. Farnesylated protein binding is the informative replacement. Proposed replacements: farnesylated protein binding Supporting Evidence: PMID:11980706 Further experiments show that H-Ras, Rheb, Rho6 and G alpha(i1) interact with PDE delta and that, at least for H-Ras, the intact C-terminus is required. |
| GO:0005515 protein binding | IPI PMID:11980706 The complex of Arl2-GTP and PDE delta: from structure to fun... | MODIFY | Summary: Protein binding with mouse Arl2. Reason: Generic protein binding. mouse Arl2 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding Supporting Evidence: PMID:22002721 We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. |
| GO:0005515 protein binding | IPI PMID:16169070 A human protein-protein interaction network: a resource for ... | MODIFY | Summary: Protein binding with ARL3. Reason: Generic protein binding. ARL3 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding Supporting Evidence: PMID:22002721 We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. |
| GO:0005515 protein binding | IPI PMID:16169070 A human protein-protein interaction network: a resource for ... | MODIFY | Summary: Protein binding with ARL15. Reason: Generic protein binding. ARL15 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | MODIFY | Summary: Protein binding with ARL2. Reason: Generic protein binding. ARL2 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding Supporting Evidence: PMID:22002721 We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. |
| GO:0005515 protein binding | IPI PMID:18588884 Specificity of Arl2/Arl3 signaling is mediated by a ternary ... | MODIFY | Summary: Protein binding with ARL2. Reason: Generic protein binding. ARL2 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding Supporting Evidence: PMID:22002721 We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. |
| GO:0005515 protein binding | IPI PMID:18588884 Specificity of Arl2/Arl3 signaling is mediated by a ternary ... | MODIFY | Summary: Protein binding with ARL3. Reason: Generic protein binding. ARL3 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding Supporting Evidence: PMID:22002721 We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. |
| GO:0005515 protein binding | IPI PMID:21516116 Next-generation sequencing to generate interactome datasets. | MODIFY | Summary: Protein binding with ARL2. Reason: Generic protein binding. ARL2 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding Supporting Evidence: PMID:22002721 We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. |
| GO:0005515 protein binding | IPI PMID:23559067 The interplay between RPGR, PDEΞ΄ and Arl2/3 regulate the cil... | MODIFY | Summary: Protein binding with RHEB (mature, farnesylated form). Reason: RHEB (mature, farnesylated form) is a farnesylated Ras-family cargo held in the PDE6D prenyl-binding pocket. Farnesylated protein binding is the informative replacement. Proposed replacements: farnesylated protein binding Supporting Evidence: PMID:22002721 Here we report the structure of fully modified farnesylated Rheb-GDP in complex with PDEΞ΄. |
| GO:0005515 protein binding | IPI PMID:23559067 The interplay between RPGR, PDEΞ΄ and Arl2/3 regulate the cil... | REMOVE | Summary: Protein binding with RPGR (Q92834). Reason: Generic protein binding. The RPGR RCC1-like domain binds PDE6D independently of prenylation and is proposed to act as a scaffold that recruits cargo-loaded PDE6D at the transition zone. GO has no informative MF term for PDE6D for this scaffold-recruited interaction, so the generic row is removed. The interaction itself is well supported and is captured in the description and in a suggested question. Supporting Evidence: PMID:23559067 Biochemical experiments and structural considerations show that RPGR can bind with high affinity to cargo-loaded PDEΞ΄ and exposes the Arl2/Arl3-binding site on PDEΞ΄. |
| GO:0005515 protein binding | IPI PMID:23559067 The interplay between RPGR, PDEΞ΄ and Arl2/3 regulate the cil... | MODIFY | Summary: Protein binding with mouse Arl2. Reason: Generic protein binding. mouse Arl2 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding Supporting Evidence: PMID:22002721 We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. |
| GO:0005515 protein binding | IPI PMID:23559067 The interplay between RPGR, PDEΞ΄ and Arl2/3 regulate the cil... | MODIFY | Summary: Protein binding with mouse Arl3. Reason: Generic protein binding. mouse Arl3 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding Supporting Evidence: PMID:22002721 We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Protein binding with ARL2. Reason: Generic protein binding. ARL2 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding Supporting Evidence: PMID:22002721 We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Protein binding with ARL16. Reason: Generic protein binding. ARL16 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding |
| GO:0005515 protein binding | IPI PMID:25519916 The EHEC-host interactome reveals novel targets for the tran... | REMOVE | Summary: Protein binding with Q7DB77, from a high-throughput or pathogen interaction screen. Reason: Generic protein binding with no functional context and no informative MF replacement. The interaction itself is not disputed. |
| GO:0005515 protein binding | IPI PMID:26455799 The Interaction of CCDC104/BARTL1 with Arl3 and Implications... | MODIFY | Summary: Protein binding with ARL3. Reason: Generic protein binding. ARL3 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding Supporting Evidence: PMID:22002721 We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. |
| GO:0005515 protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | MODIFY | Summary: Protein binding with ARL2. Reason: Generic protein binding. ARL2 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding Supporting Evidence: PMID:22002721 We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. |
| GO:0005515 protein binding | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | REMOVE | Summary: Protein binding with RPGR (Q92834-2). Reason: Generic protein binding. The RPGR RCC1-like domain binds PDE6D independently of prenylation and is proposed to act as a scaffold that recruits cargo-loaded PDE6D at the transition zone. GO has no informative MF term for PDE6D for this scaffold-recruited interaction, so the generic row is removed. The interaction itself is well supported and is captured in the description and in a suggested question. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Protein binding with RPGR (Q92834-2). Reason: Generic protein binding. The RPGR RCC1-like domain binds PDE6D independently of prenylation and is proposed to act as a scaffold that recruits cargo-loaded PDE6D at the transition zone. GO has no informative MF term for PDE6D for this scaffold-recruited interaction, so the generic row is removed. The interaction itself is well supported and is captured in the description and in a suggested question. |
| GO:0005515 protein binding | IPI PMID:30257685 Modifying Rap1-signalling by targeting Pde6Ξ΄ is neuroprotect... | MODIFY | Summary: Protein binding with ARL3. Reason: Generic protein binding. ARL3 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding Supporting Evidence: PMID:22002721 We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. |
| GO:0005515 protein binding | IPI PMID:30257685 Modifying Rap1-signalling by targeting Pde6Ξ΄ is neuroprotect... | REMOVE | Summary: Protein binding with RPGR (Q92834). Reason: Generic protein binding. The RPGR RCC1-like domain binds PDE6D independently of prenylation and is proposed to act as a scaffold that recruits cargo-loaded PDE6D at the transition zone. GO has no informative MF term for PDE6D for this scaffold-recruited interaction, so the generic row is removed. The interaction itself is well supported and is captured in the description and in a suggested question. Supporting Evidence: PMID:30257685 In absence of the compound, a host of previously described Pde6Ξ΄ binding partners were identified, including Arl3 and RPGR |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MODIFY | Summary: Protein binding with ARL2. Reason: Generic protein binding. ARL2 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding Supporting Evidence: PMID:22002721 We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MODIFY | Summary: Protein binding with ARL16. Reason: Generic protein binding. ARL16 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Protein binding with ARL2. Reason: Generic protein binding. ARL2 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding Supporting Evidence: PMID:22002721 We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Protein binding with ARL3. Reason: Generic protein binding. ARL3 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding Supporting Evidence: PMID:22002721 We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Protein binding with ARL16. Reason: Generic protein binding. ARL16 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding with Q5XKR4, from a high-throughput or pathogen interaction screen. Reason: Generic protein binding with no functional context and no informative MF replacement. The interaction itself is not disputed. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Protein binding with ARL15. Reason: Generic protein binding. ARL15 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Protein binding with ARL2. Reason: Generic protein binding. ARL2 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding Supporting Evidence: PMID:22002721 We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Protein binding with ARL3. Reason: Generic protein binding. ARL3 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding Supporting Evidence: PMID:22002721 We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Protein binding with RPGR (Q92834). Reason: Generic protein binding. The RPGR RCC1-like domain binds PDE6D independently of prenylation and is proposed to act as a scaffold that recruits cargo-loaded PDE6D at the transition zone. GO has no informative MF term for PDE6D for this scaffold-recruited interaction, so the generic row is removed. The interaction itself is well supported and is captured in the description and in a suggested question. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: Protein binding with ARL3. Reason: Generic protein binding. ARL3 is an Arf-like small GTPase. ARL2 and ARL3 bind PDE6D in their GTP-bound state and act as allosteric release factors for its prenylated cargo. Small GTPase binding is the informative replacement. Proposed replacements: small GTPase binding Supporting Evidence: PMID:22002721 We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. |
| GO:0005515 protein binding | IPI PMID:9712853 The rod cGMP phosphodiesterase delta subunit dissociates the... | MODIFY | Summary: Protein binding with RAB13. Reason: RAB13 is a prenylated small GTPase that PDE6D extracts from membranes. Small GTPase binding is the informative replacement and is also annotated by IPI from this paper. Proposed replacements: small GTPase binding Supporting Evidence: PMID:9712853 The delta-PDE binds specifically to Rab13. |
| GO:0005515 protein binding | IPI PMID:9990021 The retinitis pigmentosa GTPase regulator, RPGR, interacts w... | REMOVE | Summary: Protein binding with RPGR (Q92834). Reason: Generic protein binding. The RPGR RCC1-like domain binds PDE6D independently of prenylation and is proposed to act as a scaffold that recruits cargo-loaded PDE6D at the transition zone. GO has no informative MF term for PDE6D for this scaffold-recruited interaction, so the generic row is removed. The interaction itself is well supported and is captured in the description and in a suggested question. Supporting Evidence: PMID:9990021 In a yeast two-hybrid screen we identified the delta subunit of rod cyclic GMP phosphodiesterase (PDEdelta) as interacting with the RCC1-like domain (RLD) of RPGR (RPGR392). |
| GO:0005515 protein binding | IPI PMID:9990021 The retinitis pigmentosa GTPase regulator, RPGR, interacts w... | REMOVE | Summary: Protein binding with RPGR (Q92834-2). Reason: Generic protein binding. The RPGR RCC1-like domain binds PDE6D independently of prenylation and is proposed to act as a scaffold that recruits cargo-loaded PDE6D at the transition zone. GO has no informative MF term for PDE6D for this scaffold-recruited interaction, so the generic row is removed. The interaction itself is well supported and is captured in the description and in a suggested question. Supporting Evidence: PMID:9990021 In a yeast two-hybrid screen we identified the delta subunit of rod cyclic GMP phosphodiesterase (PDEdelta) as interacting with the RCC1-like domain (RLD) of RPGR (RPGR392). |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasm, by phylogenetic inference. Reason: PDE6D is a soluble cytoplasmic carrier of prenylated proteins. |
| GO:0005829 cytosol | IDA PMID:9712853 The rod cGMP phosphodiesterase delta subunit dissociates the... | ACCEPT | Summary: Cytosolic delta-PDE that dissociates Rab13 from membranes. Reason: The cytosol is where PDE6D carries solubilized prenylated cargo. Supporting Evidence: PMID:9712853 Purified recombinant delta-PDE had the capacity to dissociate Rab13 from cellular membranes. |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: Cytosol, from the UniProt subcellular location mapping. Reason: Core location. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624954 | ACCEPT | Summary: Cytosol, Reactome reaction (cargo trafficking to the cilium). Reason: Core location. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624956 | ACCEPT | Summary: Cytosol, Reactome reaction. Reason: Core location. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9654523 | ACCEPT | Summary: Cytosol, Reactome reaction (RAS trafficking). Reason: Core location. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9654525 | ACCEPT | Summary: Cytosol, Reactome reaction (RAS trafficking). Reason: Core location. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9654533 | ACCEPT | Summary: Cytosol, Reactome reaction (RAS trafficking). Reason: Core location. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9656781 | ACCEPT | Summary: Cytosol, Reactome reaction (RAS trafficking). Reason: Core location. |
| GO:0005929 cilium | TAS Reactome:R-HSA-5624953 | KEEP AS NON CORE | Summary: Cilium, Reactome reaction for ARL3-mediated release of farnesylated cargo. Reason: PDE6D brings cargo to the ciliary base/transition zone and proximal cilium, where ARL3-GTP releases it. PDE6D itself is mainly cytosolic, so the cilium is a site of cargo hand-off rather than a residence. Supporting Evidence: PMID:24166846 with PDE6D localized to the transition zone and proximal end of the cilium while INPP5E localized uniformly along the length of the axoneme |
| GO:0005929 cilium | TAS Reactome:R-HSA-5624954 | KEEP AS NON CORE | Summary: Cilium, Reactome reaction. Reason: As for the other Reactome cilium rows. |
| GO:0005929 cilium | TAS Reactome:R-HSA-5638012 | KEEP AS NON CORE | Summary: Cilium, Reactome reaction. Reason: As for the other Reactome cilium rows. |
| GO:0007601 visual perception | TAS PMID:9570951 Characterization of human and mouse rod cGMP phosphodiestera... | KEEP AS NON CORE | Summary: Visual perception, from the cloning paper describing PDE delta as a factor that detaches PDE6 from rod outer segment membranes. Reason: PDE6D supports photoreceptor function by trafficking prenylated phototransduction proteins (GRK1, PDE6). It does not take part in phototransduction itself. Kept as a non-core physiological role. Supporting Evidence: PMID:9570951 A novel subunit, termed PDE delta (HGMW-approved symbol, PDE6D; MW 17 kDa), is able to detach PDE partially from bovine rod outer segment membranes under physiological conditions. |
| GO:0030659 cytoplasmic vesicle membrane | EXP PMID:9712853 The rod cGMP phosphodiesterase delta subunit dissociates the... | KEEP AS NON CORE | Summary: VSV-tagged delta-PDE in vesicular structures near the plasma membrane of epithelial cells. Reason: Experimental observation of an overexpressed tagged protein, retained. PDE6D is mainly a soluble carrier, and vesicle association is not its core location. Supporting Evidence: PMID:9712853 Immunofluorescence microscopic studies revealed that the vesicular stomatitis virus (VSV)-tagged delta-PDE is localized in vesicular structures accumulated near the plasma membrane in epithelial cells. |
| GO:0030659 cytoplasmic vesicle membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cytoplasmic vesicle membrane, from the UniProt subcellular location mapping. Reason: As for the EXP row. |
| GO:0031267 small GTPase binding | IPI PMID:9712853 The rod cGMP phosphodiesterase delta subunit dissociates the... | ACCEPT | Summary: Delta-PDE binds Rab13 specifically (yeast two-hybrid) and dissociates it from membranes. Reason: Experimental support. Rab13 is a prenylated small GTPase cargo. PDE6D also binds the small GTPases ARL2 and ARL3, which release its cargo. Supporting Evidence: PMID:9712853 The delta-PDE binds specifically to Rab13. |
| GO:0031410 cytoplasmic vesicle | IDA PMID:9712853 The rod cGMP phosphodiesterase delta subunit dissociates the... | KEEP AS NON CORE | Summary: Cytoplasmic vesicle localization of tagged delta-PDE. Reason: As for the cytoplasmic vesicle membrane rows. Supporting Evidence: PMID:9712853 Immunofluorescence microscopic studies revealed that the vesicular stomatitis virus (VSV)-tagged delta-PDE is localized in vesicular structures accumulated near the plasma membrane in epithelial cells. |
| GO:0032391 photoreceptor connecting cilium | IC PMID:17496142 Deletion of PrBP/delta impedes transport of GRK1 and PDE6 ca... | KEEP AS NON CORE | Summary: Photoreceptor connecting cilium, inferred by curator from the Pde6d-knockout mouse study. Reason: Pde6d-null rods mislocalize prenylated GRK1 and PDE6, which implies that PrBP/delta acts in transport through the connecting cilium. The inference is reasonable, but the location is not core for a broadly cytosolic carrier. Supporting Evidence: PMID:17496142 Thus the absence of PrBP/delta in retina impairs transport of prenylated proteins, particularly GRK1 and cone PDE, to rod and cone outer segments |
| GO:0050953 sensory perception of light stimulus | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Sensory perception of light stimulus, from InterPro (PDE6 delta subunit family). Reason: Indirect physiological role, through trafficking of phototransduction proteins. |
| GO:0061512 protein localization to cilium | IEA GO_REF:0000107 | ACCEPT | Summary: Protein localization to cilium, by Ensembl Compara transfer from mouse. Reason: Core process. Human PDE6D binds farnesylated INPP5E and is required for its ciliary targeting. As the carrier, PDE6D does part of the localization work. Supporting Evidence: PMID:24166846 depletion of PDE6D with two independent siRNAs led to a virtually complete loss of ciliary INPP5E, suggesting that PDE6D is indispensible for proper INPP5E ciliary targeting |
| GO:0061512 protein localization to cilium | ISS GO_REF:0000024 | ACCEPT | Summary: Protein localization to cilium, by similarity to mouse. Reason: Core process, as for the IEA row. |
| GO:0140104 molecular carrier activity | IEA GO_REF:0000107 | ACCEPT | Summary: Molecular carrier activity, by Ensembl Compara transfer. Reason: Core MF. PDE6D binds prenylated proteins, moves with them through the cytosol, and releases them when ARL2/ARL3-GTP binds. Supporting Evidence: PMID:11980706 We suggest PDE delta to be a specific soluble transport factor for certain prenylated proteins and Arl2-GTP a regulator of PDE delta-mediated transport. PMID:22002721 We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. file:human/PDE6D/PDE6D-deep-research-falcon.md Structural analysis of a PDEΞ΄βfarnesylated RHEB complex places the lipid chain inside that cavity |
| GO:0140104 molecular carrier activity | ISS GO_REF:0000024 | ACCEPT | Summary: Molecular carrier activity, by similarity. Reason: Core MF, as for the IEA row. |
| GO:0001918 farnesylated protein binding | IDA PMID:22002721 Arl2-GTP and Arl3-GTP regulate a GDI-like transport system f... | NEW | Summary: PDE6D binds the farnesyl moiety of prenylated cargo in its hydrophobic pocket. This is shown by the crystal structure of fully modified farnesylated Rheb with PDEdelta, by prenylation-dependent binding of INPP5E, and by small molecules that compete for the prenyl-binding pocket and displace KRAS. Reason: This is the specific molecular basis of PDE6D's carrier activity, and it is supported directly by structural and biochemical evidence. GOA currently has only the generic molecular carrier activity and many protein-binding rows with prenylated partners (HRAS, RHEB, RAB13). Farnesylated protein binding (GO:0001918) records the cargo-recognition activity informatively. Supporting Evidence: PMID:22002721 Here we report the structure of fully modified farnesylated Rheb-GDP in complex with PDEΞ΄. PMID:23698361 Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEΞ΄, which sustains the spatial organization of KRAS by facilitating its diffusion in the cytoplasm. PMID:24166846 Having determined that both the PDE6D-INPP5E interaction and proper INPP5E ciliary localization requires prenylation |
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Download this section (compressed HTML)Q: Should a process term for PDE6D-mediated maintenance of Ras plasma-membrane localization be annotated, or is the carrier activity alone the right representation? Other GDI-like carriers (RhoGDIs, UNC119) would be the comparators to check.
Q: Is RPGR binding (via its RCC1-like domain) a scaffold that recruits cargo-loaded PDE6D at the transition zone in non-photoreceptor cilia, or is it photoreceptor-specific?
Experiment: In PDE6D-knockout RPE1 cells, compare rescue of ciliary INPP5E and plasma-membrane KRAS localization by wild-type PDE6D and by mutants that selectively lose ARL3 or ARL2 binding.
Hypothesis: The ciliary and Ras-trafficking roles of PDE6D can be separated by cargo-specific release factors (ARL3 versus ARL2).
Type: knockout rescue with separation-of-function mutants
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