Recombinant Human Protein RD3 (RD3)

Function

Plays a critical role in the regulation of enzymes involved in nucleotide cycle in photoreceptors (PubMed:21078983, PubMed:21928830, PubMed:27471269, PubMed:29515371, PubMed:30559291). Inhibits the basal catalytic activity and the GCAP-stimulated activity of GUCY2D and GUCY2F, two retinal guanylyl cyclases involved in the production of cGMP in photoreceptors (PubMed:21928830, PubMed:27471269, PubMed:29515371, PubMed:30559291). Involved in the transport of GUCY2D and GUCY2F to their target sites in the photoreceptor outer segment (PubMed:21078983). Up-regulates the activity of GUK1, a kinase that also plays an essential role for recycling GMP and indirectly, cGMP (PubMed:29515371). Plays an important role for the survival of rods and cones in the retina (By similarity)

Subcellular Location

Cell projection, cilium, photoreceptor outer segment; Photoreceptor inner segment; Endosome; Nucleus; Cytoplasm; Cytoplasm, perinuclear region

Disease Association

Leber congenital amaurosis 12 (LCA12) : A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Expressed in retina (PubMed:12914764). Widely expressed (at protein level) (PubMed:29030614). In the retina the strongest immunoreactivity is detected in the inner half of the cytoplasmic portion of the photoreceptor layer, where rods and cones are found, and the external half of the outer plexiform layer (at protein level) (PubMed:29030614)

Subunit

Monomer (PubMed:30559291). Interacts with GUCY2D; negatively regulates its activity (PubMed:21928830, PubMed:26100624, PubMed:27471269, PubMed:30559291). The interaction with GUCY2D promotes the exit of GUCY2D from the endoplasmic reticulum and its trafficking to the photoreceptor outer segments (PubMed:21078983). Interacts with GUCY2F (By similarity). The interaction with GUCY2F negatively regulates GUCY2F activity (PubMed:29515371). The interaction with GUCY2F promotes the exit of GUCY2F from the endoplasmic reticulum and its trafficking to the photoreceptor outer segments (PubMed:21078983). Interacts with GUK1; up-regulates GUK1 activity (PubMed:29515371)

• Lavorgna G. et al. Identification and characterization of C1orf36, a transcript highly expressed in photoreceptor cells, and mutation analysis in retinitis pigmentosa. — Biochem. Biophys. Res. Commun. (2003)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Mural R.J. et al. PubMed: CI-5GBD0VIIJ7C63 (SEP-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Friedman J.S. et al. Premature truncation of a novel protein, RD3, exhibiting subnuclear localization is associated with retinal degeneration. — Am. J. Hum. Genet. (2006)
• Azadi S. et al. RD3, the protein associated with Leber congenital amaurosis type 12, is required for guanylate cyclase trafficking in photoreceptor cells. — Proc. Natl. Acad. Sci. U.S.A. (2010)
• Peshenko I.V. et al. Retinal degeneration 3 (RD3) protein inhibits catalytic activity of retinal membrane guanylyl cyclase (RetGC) and its stimulation by activating proteins. — Biochemistry (2011)
• Peshenko I.V. et al. Dimerization Domain of Retinal Membrane Guanylyl Cyclase 1 (RetGC1) Is an Essential Part of Guanylyl Cyclase-activating Protein (GCAP) Binding Interface. — J. Biol. Chem. (2015)