| Structural highlights
Disease
SNX10_HUMAN Autosomal recessive malignant osteopetrosis. The disease is caused by mutations affecting the gene represented in this entry.[1] [2] [3]
Function
SNX10_HUMAN Probable phosphoinositide-binding protein involved in protein sorting and membrane trafficking in endosomes. Plays a role in cilium biogenesis through regulation of the transport and the localization of proteins to the cilium. Required for the localization to the cilium of V-ATPase subunit ATP6V1D and ATP6V0D1, and RAB8A. Involved in osteoclast differentiation and therefore bone resorption.[4] [5] [6]
Publication Abstract from PubMed
Sorting nexin 10 (SNX10), the unique member of the SNX family having vacuolation activity in cells, was shown to be involved in the development of autosomal recessive osteopetrosis (ARO) in recent genetic studies. However, the molecular mechanism of the disease-related mutations affecting the biological function of SNX10 is unclear. Here, we report the crystal structure of human SNX10 to 2.6A resolution. The structure reveals that SNX10 contains the extended phox-homology domain we previously proposed. Our study provides the structural details of those disease-related mutations. Combined with the vacuolation study of those mutations, we found that Tyr32 and Arg51 are important for the protein stability and both play a critical role in vacuolation activity, while Arg16Leu may affect the function of SNX10 in osteoclast through protein-protein interactions. Proteins 2014; 82:3483-3489. (c) 2014 Wiley Periodicals, Inc.
Structure of human SNX10 reveals insights into its role in human autosomal recessive osteopetrosis.,Xu T, Xu J, Ye Y, Wang Q, Shu X, Pei D, Liu J Proteins. 2014 Dec;82(12):3483-9. doi: 10.1002/prot.24689. Epub 2014 Oct 1. PMID:25212774[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Aker M, Rouvinski A, Hashavia S, Ta-Shma A, Shaag A, Zenvirt S, Israel S, Weintraub M, Taraboulos A, Bar-Shavit Z, Elpeleg O. An SNX10 mutation causes malignant osteopetrosis of infancy. J Med Genet. 2012 Apr;49(4):221-6. doi: 10.1136/jmedgenet-2011-100520. PMID:22499339 doi:http://dx.doi.org/10.1136/jmedgenet-2011-100520
- ↑ Megarbane A, Pangrazio A, Villa A, Chouery E, Maarawi J, Sabbagh S, Lefranc G, Sobacchi C. Homozygous stop mutation in the SNX10 gene in a consanguineous Iraqi boy with osteopetrosis and corpus callosum hypoplasia. Eur J Med Genet. 2013 Jan;56(1):32-5. doi: 10.1016/j.ejmg.2012.10.010. Epub 2012 , Oct 31. PMID:23123320 doi:http://dx.doi.org/10.1016/j.ejmg.2012.10.010
- ↑ Pangrazio A, Fasth A, Sbardellati A, Orchard PJ, Kasow KA, Raza J, Albayrak C, Albayrak D, Vanakker OM, De Moerloose B, Vellodi A, Notarangelo LD, Schlack C, Strauss G, Kuhl JS, Caldana E, Lo Iacono N, Susani L, Kornak U, Schulz A, Vezzoni P, Villa A, Sobacchi C. SNX10 mutations define a subgroup of human autosomal recessive osteopetrosis with variable clinical severity. J Bone Miner Res. 2013 May;28(5):1041-9. doi: 10.1002/jbmr.1849. PMID:23280965 doi:http://dx.doi.org/10.1002/jbmr.1849
- ↑ Qin B, He M, Chen X, Pei D. Sorting nexin 10 induces giant vacuoles in mammalian cells. J Biol Chem. 2006 Dec 1;281(48):36891-6. Epub 2006 Sep 29. PMID:17012226 doi:http://dx.doi.org/10.1074/jbc.M608884200
- ↑ Chen Y, Wu B, Xu L, Li H, Xia J, Yin W, Li Z, Shi D, Li S, Lin S, Shu X, Pei D. A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and in vivo. Cell Res. 2012 Feb;22(2):333-45. doi: 10.1038/cr.2011.134. Epub 2011 Aug 16. PMID:21844891 doi:http://dx.doi.org/10.1038/cr.2011.134
- ↑ Aker M, Rouvinski A, Hashavia S, Ta-Shma A, Shaag A, Zenvirt S, Israel S, Weintraub M, Taraboulos A, Bar-Shavit Z, Elpeleg O. An SNX10 mutation causes malignant osteopetrosis of infancy. J Med Genet. 2012 Apr;49(4):221-6. doi: 10.1136/jmedgenet-2011-100520. PMID:22499339 doi:http://dx.doi.org/10.1136/jmedgenet-2011-100520
- ↑ Xu T, Xu J, Ye Y, Wang Q, Shu X, Pei D, Liu J. Structure of human SNX10 reveals insights into its role in human autosomal recessive osteopetrosis. Proteins. 2014 Dec;82(12):3483-9. doi: 10.1002/prot.24689. Epub 2014 Oct 1. PMID:25212774 doi:http://dx.doi.org/10.1002/prot.24689
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