3c5n

Structural highlights

Disease

TULP1_HUMAN Defects in TULP1 are the cause of retinitis pigmentosa type 14 (RP14) [MIM:600132. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP14 inheritance is autosomal recessive.^{[1] [2] [3] [4] [5]} Defects in TULP1 are the cause of Leber congenital amaurosis type 15 (LCA15) [MIM:613843. LCA15 is 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.^{[6] [7]}

Function

TULP1_HUMAN Required for normal development of photoreceptor synapses. Required for normal photoreceptor function and for long-term survival of photoreceptor cells. Interacts with cytoskeleton proteins and may play a role in protein transport in photoreceptor cells (By similarity). Binds lipids, especially phosphatidylinositol 3-phosphate, phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,4-bisphosphate, phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 3,4,5-bisphosphate, phosphatidylserine and phosphatidic acid (in vitro). Contribute to stimulation of phagocytosis of apoptotic retinal pigment epithelium (RPE) cells and macrophages.^{[8] [9]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Caberoy NB, Maiguel D, Kim Y, Li W. Identification of tubby and tubby-like protein 1 as eat-me signals by phage display. Exp Cell Res. 2010 Jan 15;316(2):245-57. doi: 10.1016/j.yexcr.2009.10.008. Epub, 2009 Oct 22. PMID:19837063 doi:10.1016/j.yexcr.2009.10.008
2. ↑ Gu S, Lennon A, Li Y, Lorenz B, Fossarello M, North M, Gal A, Wright A. Tubby-like protein-1 mutations in autosomal recessive retinitis pigmentosa. Lancet. 1998 Apr 11;351(9109):1103-4. PMID:9660588 doi:10.1016/S0140-6736(05)79384-3
3. ↑ Hagstrom SA, North MA, Nishina PL, Berson EL, Dryja TP. Recessive mutations in the gene encoding the tubby-like protein TULP1 in patients with retinitis pigmentosa. Nat Genet. 1998 Feb;18(2):174-6. PMID:9462750 doi:10.1038/ng0298-174
4. ↑ Kondo H, Qin M, Mizota A, Kondo M, Hayashi H, Hayashi K, Oshima K, Tahira T, Hayashi K. A homozygosity-based search for mutations in patients with autosomal recessive retinitis pigmentosa, using microsatellite markers. Invest Ophthalmol Vis Sci. 2004 Dec;45(12):4433-9. PMID:15557452 doi:10.1167/iovs.04-0544
5. ↑ den Hollander AI, van Lith-Verhoeven JJ, Arends ML, Strom TM, Cremers FP, Hoyng CB. Novel compound heterozygous TULP1 mutations in a family with severe early-onset retinitis pigmentosa. Arch Ophthalmol. 2007 Jul;125(7):932-5. PMID:17620573 doi:10.1001/archopht.125.7.932
6. ↑ Hanein S, Perrault I, Gerber S, Tanguy G, Barbet F, Ducroq D, Calvas P, Dollfus H, Hamel C, Lopponen T, Munier F, Santos L, Shalev S, Zafeiriou D, Dufier JL, Munnich A, Rozet JM, Kaplan J. Leber congenital amaurosis: comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis. Hum Mutat. 2004 Apr;23(4):306-17. PMID:15024725 doi:10.1002/humu.20010
7. ↑ Mataftsi A, Schorderet DF, Chachoua L, Boussalah M, Nouri MT, Barthelmes D, Borruat FX, Munier FL. Novel TULP1 mutation causing leber congenital amaurosis or early onset retinal degeneration. Invest Ophthalmol Vis Sci. 2007 Nov;48(11):5160-7. PMID:17962469 doi:10.1167/iovs.06-1013
8. ↑ Xi Q, Pauer GJ, Marmorstein AD, Crabb JW, Hagstrom SA. Tubby-like protein 1 (TULP1) interacts with F-actin in photoreceptor cells. Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4754-61. PMID:16303976 doi:10.1167/iovs.05-0693
9. ↑ Caberoy NB, Maiguel D, Kim Y, Li W. Identification of tubby and tubby-like protein 1 as eat-me signals by phage display. Exp Cell Res. 2010 Jan 15;316(2):245-57. doi: 10.1016/j.yexcr.2009.10.008. Epub, 2009 Oct 22. PMID:19837063 doi:10.1016/j.yexcr.2009.10.008