1. Figure 3 The genomic organization and protein architecture of OCRL
Figure 3 | The genomic organization and protein architecture of OCRL. a | Genomic organization of the OCRL gene. OCRL is composed of 23 exons and 22 introns (shown to scale). Exons 2–5 encode the pleckstrin homology (PH)-like domain, exons 9–15 encode the 5-phosphatase catalytic domain and exons 16–22 encode the ASPM, SPD-2, Hydin (ASH) and RhoGAP-like domains of the OCRL protein. Specific mutations that cause Lowe syndrome are shown above the gene whereas mutations that cause Dent disease 2 are shown below. The highlighted mutations (821T>C, 952C>T, 1568G>A and 1567G>A) have been identified as causing both Lowe syndrome and Dent disease 2; their corresponding amino acid changes are shown in brackets. The horizontal dotted lines represent gross genomic deletions. b | Organization of domains in the full-length OCRL protein. The PH domain in the N-terminal region is not associated with the membrane bilayer and is connected by a linker region to the 5-phosphatase domain, which recognizes PI(4,5)P2 on the membrane (red headgroup). The ASH domain and the RhoGAP-like domain are characterized by the presence of a large number of sites that mediate interaction of OCRL with its partners (for example, Rab GTPases, proteins involved in endocytosis such as APPL1 and Ses1/2, and proteins associated with actin polymerization such as Cdc42 and Rac1). The sites of interaction with clathrin and AP2 are indicated.
De Matteis, M. A. et al. (2017) The 5‑phosphatase OCRL in Lowe syndrome and Dent disease 2
Nat. Rev. Nephrol. doi: /nrneph