Retinitis pigmentosa GTPase regulator-interacting protein 1 (RPGRIP1) specifically interacts with retinitis pigmentosa GTPase regulator (RPGR) []. Mutations in RPGR cause X-linked retinitis pigmentosa type 3 (RP3), whereas mutations in RPGRIP1 cause Leber congenital amaurosis (LCA) []. RPGRIP1 is expressed in the retina and is present in the connecting cilium and outer segments of photoreceptors, where it partially co-localises with RPGR [, ]. RPGR isoforms seem to determine the subcellular targeting of RPGRIP1 [].
RPGR-interacting protein 1 (RPGRIP1) is mutated in the eye disease Leber congenital amaurosis (LCA) and its structural homologue, RPGRIP1-like (RPGRIP1L, also called NPHP8 or fantom), is mutated in many different ciliopathies [, ]. Both are multidomain proteins that are predicted to interact with retinitis pigmentosa G-protein regulator (RPGR) []. Both consist of an N-terminal coiled coil domain, two C2 domains (C2N and C2C), and a C-terminal RPGR-interacting domain (RID). RID is a C2 domain with a canonical beta sandwich structure that does not bind Ca2+ and/or phospholipids and thus constitutes a unique type of protein-protein interaction module [].Both RPGRIP1 and RPGRIP1L interact with the ciliary transition zone protein nephrocystin 4 (NPHP4) via their C2C domain [, ]. An hypothesis is that RPGRIP1 and RPGRIP1L function as cilium-specific scaffolds that recruit a Nek4 signaling network which regulates cilium stability []. The expression of RPGRIP1 seems to be limited to photoreceptors and amacrine cells in the retina [], whereas RPGRIP1L is found in other tissues as well.
This is the C-terminal domain of retinitis pigmentosa G-protein regulator (RPGR) interacting protein-1 (RPGRIP1) present in Homo sapiens. A mutation in RPGRIP1 can be observed in the eye disease Leber congenital amaurosis. The domain is commonly known as the RPGR-interacting domain (RID) and is thought to have a C2-like fold [].
