Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta

Function

Promotes the release of prenylated target proteins from cellular membranes. Modulates the activity of prenylated or palmitoylated Ras family members by regulating their subcellular location. Required for normal ciliary targeting of farnesylated target proteins, such as INPP5E. Required for RAB28 localization to the cone cell outer segments in the retina (By similarity). Modulates the subcellular location of target proteins by acting as a GTP specific dissociation inhibitor (GDI) (By similarity). Increases the affinity of ARL3 for GTP by several orders of magnitude. Stabilizes ARL3-GTP by decreasing the nucleotide dissociation rate (By similarity).

Classification

Family (Pfam)

PF05351 GMP_PDE_delta

InterPro

Ig_E-set, PDED_dom, PDED_dom_sf, Rhodop-sen_GMP-Pdiesterase_dsu

Functional cluster

Small GTPases (Ras/Rab) & related

Experimental structures · PDB · 38

• 1KSG X-ray 2.30A
• 1KSH X-ray 1.80A
• 1KSJ X-ray 2.60A
• 3T5G X-ray 1.70A
• 3T5I X-ray 2.10A
• 4JHP X-ray 1.90A
• 4JV6 X-ray 1.87A
• 4JV8 X-ray 1.45A
• 4JVB X-ray 1.75A
• 4JVF X-ray 2.40A
• 5E80 X-ray 2.60A
• 5E8F X-ray 2.10A
• … and 26 more

A predicted model is available from AlphaFold.

Gene Ontology · 8

• GO:0005929 cilium
• GO:0005737 cytoplasm
• GO:0031410 cytoplasmic vesicle
• GO:0030659 cytoplasmic vesicle membrane
• GO:0005829 cytosol
• GO:0005095 GTPase inhibitor activity
• GO:0031267 small GTPase binding
• GO:0007601 visual perception

Disease associations

• Joubert syndrome 22 MONDO:0014297

Drugs targeting this protein · 2

• PENTOXIFYLLINE inhibitor
• DIPYRIDAMOLE inhibitor

Related proteins · sequence + function similarity

• Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta 1.00
• Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta 1.00
• Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta 0.99
• Phosphodiesterase delta-like protein 0.91
• Probable cGMP 3',5'-cyclic phosphodiesterase subunit delta 0.85
• Probable cGMP 3',5'-cyclic phosphodiesterase subunit delta 0.85
• Probable cGMP 3',5'-cyclic phosphodiesterase subunit delta 0.83
• Probable cGMP 3',5'-cyclic phosphodiesterase subunit delta 0.83
• Probable cGMP 3',5'-cyclic phosphodiesterase subunit delta 0.83
• Probable cGMP 3',5'-cyclic phosphodiesterase subunit delta 0.83
• Probable cGMP 3',5'-cyclic phosphodiesterase subunit delta 0.82
• Probable cGMP 3',5'-cyclic phosphodiesterase subunit delta 0.82

Co-cited proteins · studied together in the literature

• Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta 4 shared papers
• Phosphatidylinositol polyphosphate 5-phosphatase type IV 1 shared papers
• X-linked retinitis pigmentosa GTPase regulator 2 shared papers
• ADP-ribosylation factor-like protein 2 1 shared papers
• Ras-related protein Rab-13 1 shared papers
• ADP-ribosylation factor-like protein 3 1 shared papers
• GTP-binding protein Rheb 1 shared papers
• GTPase KRas 1 shared papers
• X-linked retinitis pigmentosa GTPase regulator 1 shared papers
• GTPase HRas 1 shared papers

Literature · 13 cited papers

• A homozygous PDE6D mutation in Joubert syndrome impairs targeting of farnesylated INPP5E protein to the primary cilium. Hum. Mutat. · 2014
• Small molecule inhibition of the KRAS-PDE? interaction impairs oncogenic KRAS signalling. Nature · 2013
• The interplay between RPGR, PDE? and Arl2/3 regulate the ciliary targeting of farnesylated cargo. EMBO Rep. · 2013
• Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for farnesylated cargo. Nat. Chem. Biol. · 2011
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• The complex of Arl2-GTP and PDE delta: from structure to function. EMBO J. · 2002
• The delta subunit of rod specific cyclic GMP phosphodiesterase, PDE delta, interacts with the Arf-like protein Arl3 in a GTP specific manner. FEBS Lett. · 1999
• The retinitis pigmentosa GTPase regulator, RPGR, interacts with the delta subunit of rod cyclic GMP phosphodiesterase. Proc. Natl. Acad. Sci. U.S.A. · 1999
• Cloning and gene structure of the rod cGMP phosphodiesterase delta subunit gene (PDED) in man and mouse. Eur. J. Hum. Genet. · 1998
• The rod cGMP phosphodiesterase delta subunit dissociates the small GTPase Rab13 from membranes. J. Biol. Chem. · 1998
• Characterization of human and mouse rod cGMP phosphodiesterase delta subunit (PDE6D) and chromosomal localization of the human gene. Genomics · 1998
• … and 1 more in the literature graph