PDE6D (O43924) research notes

Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta (PDEdelta, PrBP/delta), human. A prenyl-binding, GDI-like carrier.

Deep research status

Falcon deep research succeeded (PDE6D-deep-research-falcon.md; the first attempt with the 600 s default timed out, and the rerun with --timeout 2400 succeeded). Its summary agrees with the publication-based review below. The review's supporting quotes come from the cached publications.

Summary of function

• Original description: PMID:9570951
• Carrier of prenylated proteins, regulated by Arl2-GTP: [PMID:11980706 "PDE delta is structurally closely related to RhoGDI and contains a deep empty hydrophobic pocket."; "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."]
• Farnesyl binding and Arl2/Arl3 release: [PMID:22002721 "Here we report the structure of fully modified farnesylated Rheb-GDP in complex with PDEδ."; "We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo."]
• RAS (non-ciliary): PMID:23698361 Also Rap1 in retina (PMID:30257685).
• Cilia: INPP5E targeting, Joubert syndrome. PMID:24166846. Not required for ciliogenesis PMID:24166846.
• Photoreceptors: PMID:17496142
• RPGR scaffold: PMID:23559067
• Rab13: PMID:9712853

Key curation decisions

• Core MF: molecular carrier activity (GO:0140104; IEA/ISS accepted). NEW: farnesylated protein binding (GO:0001918, verified in OLS), IDA from PMID:22002721. This is the cargo-recognition MF and is directly supported by structure and by binding of KRAS, RHEB and INPP5E.
• Protein binding rows: ARL2/ARL3/ARL15/ARL16 changed (MODIFY) to small GTPase binding. HRAS and RHEB changed to farnesylated protein binding. RAB13 changed to small GTPase binding. RPGR rows, tir (EHEC), OTP: REMOVE (generic). The RPGR scaffold relationship is noted in the description and a suggested question.
• GTPase inhibitor activity (IEA/ISS): KEEP_AS_NON_CORE. It is a consequence of binding ARL2/3-GTP, not the evolved function.
• Cilium (Reactome TAS): KEEP_AS_NON_CORE. PDE6D is mainly cytosolic and hands off cargo at the transition zone and proximal cilium.
• No NEW process term for Ras plasma-membrane localization. It is raised as a suggested question, with RhoGDI/UNC119 comparators to be checked first, per CLAUDE.md's bar for NEW process terms.

HPA cilium atlas vs module role

• Module stage 5: "Lipidated cargo carriers" (PDE6D with UNC119B); "Carry lipidated proteins to the cilium for ARL3-dependent release"; process protein localization to cilium.
• HPA v25: no cilium, basal body or centrosome call; main location Vesicles. This is consistent with PDE6D being a soluble cytosolic carrier, enriched only transiently near the transition zone (PMID:24166846). It is not a resident ciliary protein, so no HPA ciliary call is expected.
• Assessment: core_functions agrees with the module's ciliary-carrier role, framed as cytosolic carrier activity plus protein localization to cilium. It adds a separate, cilium-independent core function: solubilization of farnesylated Ras-family GTPases (KRAS, HRAS, RHEB). The module's stage-5 placement is a correct but partial view of PDE6D. It should not be read as PDE6D being a cilium-specific protein.