RPGRIP1 explained

X-linked retinitis pigmentosa GTPase regulator-interacting protein 1 is a protein in the ciliary transition zone that in humans is encoded by the RPGRIP1 gene.^{[1] [2]} RPGRIP1 is a multi-domain protein containing a coiled-coil domain at the N-terminus, two C2 domains and a C-terminal RPGR-interacting domain (RID). Defects in the gene result in the Leber congenital amaurosis (LCA) syndrome^[3] and in the eye disease glaucoma.^[4]

Interactions

RPGRIP1 has been shown to interact with Retinitis pigmentosa GTPase regulator.^[5] RPGRIP1 interacts with RPGR via its RPGR-interacting domain (RID), which folds into a C2 domain architecture and interacts with RPGR at three different locations: A β strand of the RID interacting with the large loop of RPGR, at a hydrophobic interaction site, and via the N-terminal region of the RID.^[6]

Further reading

• Hong DH, Yue G, Adamian M, Li T . Retinitis pigmentosa GTPase regulator (RPGRr)-interacting protein is stably associated with the photoreceptor ciliary axoneme and anchors RPGR to the connecting cilium . The Journal of Biological Chemistry . 276 . 15 . 12091–9 . April 2001 . 11104772 . 10.1074/jbc.M009351200 . free .
• Gerber S, Perrault I, Hanein S, Barbet F, Ducroq D, Ghazi I, Martin-Coignard D, Leowski C, Homfray T, Dufier JL, Munnich A, Kaplan J, Rozet JM . Complete exon-intron structure of the RPGR-interacting protein (RPGRIP1) gene allows the identification of mutations underlying Leber congenital amaurosis . European Journal of Human Genetics . 9 . 8 . 561–71 . August 2001 . 11528500 . 10.1038/sj.ejhg.5200689 . free .
• Mavlyutov TA, Zhao H, Ferreira PA . Species-specific subcellular localization of RPGR and RPGRIP isoforms: implications for the phenotypic variability of congenital retinopathies among species . Human Molecular Genetics . 11 . 16 . 1899–907 . August 2002 . 12140192 . 10.1093/hmg/11.16.1899 .
• Hameed A, Abid A, Aziz A, Ismail M, Mehdi SQ, Khaliq S . Evidence of RPGRIP1 gene mutations associated with recessive cone-rod dystrophy . Journal of Medical Genetics . 40 . 8 . 616–9 . August 2003 . 12920076 . 1735563 . 10.1136/jmg.40.8.616 .
• Shu X, Fry AM, Tulloch B, Manson FD, Crabb JW, Khanna H, Faragher AJ, Lennon A, He S, Trojan P, Giessl A, Wolfrum U, Vervoort R, Swaroop A, Wright AF . RPGR ORF15 isoform co-localizes with RPGRIP1 at centrioles and basal bodies and interacts with nucleophosmin . Human Molecular Genetics . 14 . 9 . 1183–97 . May 2005 . 15772089 . 10.1093/hmg/ddi129 . free .
• Lu X, Guruju M, Oswald J, Ferreira PA . Limited proteolysis differentially modulates the stability and subcellular localization of domains of RPGRIP1 that are distinctly affected by mutations in Leber's congenital amaurosis . Human Molecular Genetics . 14 . 10 . 1327–40 . May 2005 . 15800011 . 1769350 . 10.1093/hmg/ddi143 .
• Lu X, Ferreira PA . Identification of novel murine- and human-specific RPGRIP1 splice variants with distinct expression profiles and subcellular localization . Investigative Ophthalmology & Visual Science . 46 . 6 . 1882–90 . June 2005 . 15914599 . 1769349 . 10.1167/iovs.04-1286 .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Booij JC, Florijn RJ, ten Brink JB, Loves W, Meire F, van Schooneveld MJ, de Jong PT, Bergen AA . Identification of mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa . Journal of Medical Genetics . 42 . 11 . e67 . November 2005 . 16272259 . 1735944 . 10.1136/jmg.2005.035121 .
• Roepman R, Letteboer SJ, Arts HH, van Beersum SE, Lu X, Krieger E, Ferreira PA, Cremers FP . Interaction of nephrocystin-4 and RPGRIP1 is disrupted by nephronophthisis or Leber congenital amaurosis-associated mutations . Proceedings of the National Academy of Sciences of the United States of America . 102 . 51 . 18520–5 . December 2005 . 16339905 . 1317916 . 10.1073/pnas.0505774102 . 2005PNAS..10218520R . free .
• Jacobson SG, Cideciyan AV, Aleman TS, Sumaroka A, Schwartz SB, Roman AJ, Stone EM . Leber congenital amaurosis caused by an RPGRIP1 mutation shows treatment potential . Ophthalmology . 114 . 5 . 895–8 . May 2007 . 17306875 . 10.1016/j.ophtha.2006.10.028 .
• Arts HH, Doherty D, van Beersum SE, Parisi MA, Letteboer SJ, Gorden NT, Peters TA, Märker T, Voesenek K, Kartono A, Ozyurek H, Farin FM, Kroes HY, Wolfrum U, Brunner HG, Cremers FP, Glass IA, Knoers NV, Roepman R . Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome . Nature Genetics . 39 . 7 . 882–8 . July 2007 . 17558407 . 10.1038/ng2069 . 12910768 .
• Patil H, Guruju MR, Cho KI, Yi H, Orry A, Kim H, Ferreira PA . Structural and functional plasticity of subcellular tethering, targeting and processing of RPGRIP1 by RPGR isoforms . Biology Open . 1 . 2 . 140–60 . February 2012 . 23213406 . 10.1242/bio.2011489 . 3507198.

External links

• PDBe-KB provides an overview of all the structure information available in the PDB for Human X-linked retinitis pigmentosa GTPase regulator-interacting protein 1 (RPGRIP1)

Notes and References

1. Boylan JP, Wright AF . Identification of a novel protein interacting with RPGR . Human Molecular Genetics . 9 . 14 . 2085–93 . September 2000 . 10958647 . 10.1093/hmg/9.14.2085 . free . 1842/23251 . free .
2. Web site: Entrez Gene: RPGRIP1 retinitis pigmentosa GTPase regulator interacting protein 1.
3. Dryja TP, Adams SM, Grimsby JL, McGee TL, Hong DH, Li T, Andréasson S, Berson EL . Null RPGRIP1 alleles in patients with Leber congenital amaurosis . American Journal of Human Genetics . 68 . 5 . 1295–8 . May 2001 . 11283794 . 1226111 . 10.1086/320113 .
4. Fernández-Martínez L, Letteboer S, Mardin CY, Weisschuh N, Gramer E, Weber BH, Rautenstrauss B, Ferreira PA, Kruse FE, Reis A, Roepman R, Pasutto F . Evidence for RPGRIP1 gene as risk factor for primary open angle glaucoma . European Journal of Human Genetics . 19 . 4 . 445–51 . April 2011 . 21224891 . 3060327 . 10.1038/ejhg.2010.217 .
5. Roepman R, Bernoud-Hubac N, Schick DE, Maugeri A, Berger W, Ropers HH, Cremers FP, Ferreira PA . The retinitis pigmentosa GTPase regulator (RPGR) interacts with novel transport-like proteins in the outer segments of rod photoreceptors . Human Molecular Genetics . 9 . 14 . 2095–105 . September 2000 . 10958648 . 10.1093/hmg/9.14.2095 . free .
6. Remans K, Bürger M, Vetter IR, Wittinghofer A . C2 domains as protein-protein interaction modules in the ciliary transition zone . Cell Reports . 8 . 1 . 1–9 . July 2014 . 24981858 . 10.1016/j.celrep.2014.05.049 . free . 4519163 .