2h57

Structural highlights

Disease

ARL6_HUMAN Defects in ARL6 are a cause of Bardet-Biedl syndrome type 3 (BBS3) [MIM:209900. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder characterized by usually severe pigmentary retinopathy, early onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease.^{[1] [2]} Defects in ARL6 are the cause of retinitis pigmentosa type 55 (RP55) [MIM:613575. RP55 is a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. 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.^[3]

Function

ARL6_HUMAN Involved in membrane protein trafficking at the base of the ciliary organelle. Mediates recruitment onto plasma membrane of the BBSome complex which would constitute a coat complex required for sorting of specific membrane proteins to the primary cilia. May regulate cilia assembly and disassembly and subsequent ciliary signaling events such as the Wnt signaling cascade. Isoform 2 may be required for proper retinal function and organization.^{[4] [5]}

Evolutionary Conservation

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

References

1. ↑ Chiang AP, Nishimura D, Searby C, Elbedour K, Carmi R, Ferguson AL, Secrist J, Braun T, Casavant T, Stone EM, Sheffield VC. Comparative genomic analysis identifies an ADP-ribosylation factor-like gene as the cause of Bardet-Biedl syndrome (BBS3). Am J Hum Genet. 2004 Sep;75(3):475-84. Epub 2004 Jul 16. PMID:15258860 doi:10.1086/423903
2. ↑ Fan Y, Esmail MA, Ansley SJ, Blacque OE, Boroevich K, Ross AJ, Moore SJ, Badano JL, May-Simera H, Compton DS, Green JS, Lewis RA, van Haelst MM, Parfrey PS, Baillie DL, Beales PL, Katsanis N, Davidson WS, Leroux MR. Mutations in a member of the Ras superfamily of small GTP-binding proteins causes Bardet-Biedl syndrome. Nat Genet. 2004 Sep;36(9):989-93. Epub 2004 Aug 15. PMID:15314642 doi:10.1038/ng1414
3. ↑ Aldahmesh MA, Safieh LA, Alkuraya H, Al-Rajhi A, Shamseldin H, Hashem M, Alzahrani F, Khan AO, Alqahtani F, Rahbeeni Z, Alowain M, Khalak H, Al-Hazzaa S, Meyer BF, Alkuraya FS. Molecular characterization of retinitis pigmentosa in Saudi Arabia. Mol Vis. 2009 Nov 24;15:2464-9. PMID:19956407
4. ↑ Jin H, White SR, Shida T, Schulz S, Aguiar M, Gygi SP, Bazan JF, Nachury MV. The conserved Bardet-Biedl syndrome proteins assemble a coat that traffics membrane proteins to cilia. Cell. 2010 Jun 25;141(7):1208-19. doi: 10.1016/j.cell.2010.05.015. PMID:20603001 doi:10.1016/j.cell.2010.05.015
5. ↑ Wiens CJ, Tong Y, Esmail MA, Oh E, Gerdes JM, Wang J, Tempel W, Rattner JB, Katsanis N, Park HW, Leroux MR. Bardet-Biedl syndrome-associated small GTPase ARL6 (BBS3) functions at or near the ciliary gate and modulates Wnt signaling. J Biol Chem. 2010 May 21;285(21):16218-30. Epub 2010 Mar 5. PMID:20207729 doi:10.1074/jbc.M109.070953