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Structural highlights

Disease

[CTNS_HUMAN] Juvenile nephropathic cystinosis;Ocular cystinosis;Infantile nephropathic cystinosis. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.

Function

[CTNS_HUMAN] Cystine/H(+) symporter that mediates export of cystine, the oxidized dimer of cysteine, from lysosomes (PubMed:11689434, PubMed:18337546, PubMed:22232659, PubMed:29467429, PubMed:33208952, PubMed:15128704). Plays an important role in melanin synthesis by catalyzing cystine export from melanosomes, possibly by inhibiting pheomelanin synthesis (PubMed:22649030). In addition to cystine export, also acts as a positive regulator of mTORC1 signaling in kidney proximal tubular cells, via interactions with components of the v-ATPase and Ragulator complexes (By similarity). Also involved in small GTPase-regulated vesicle trafficking and lysosomal localization of LAMP2A, independently of cystine transporter activity (By similarity).[UniProtKB:P57757]^{[1] [2] [3] [4] [5] [6] [7]}

References

1. ↑ Kalatzis V, Cherqui S, Antignac C, Gasnier B. Cystinosin, the protein defective in cystinosis, is a H(+)-driven lysosomal cystine transporter. EMBO J. 2001 Nov 1;20(21):5940-9. doi: 10.1093/emboj/20.21.5940. PMID:11689434 doi:http://dx.doi.org/10.1093/emboj/20.21.5940
2. ↑ Kalatzis V, Nevo N, Cherqui S, Gasnier B, Antignac C. Molecular pathogenesis of cystinosis: effect of CTNS mutations on the transport activity and subcellular localization of cystinosin. Hum Mol Genet. 2004 Jul 1;13(13):1361-71. doi: 10.1093/hmg/ddh152. Epub 2004 May , 5. PMID:15128704 doi:http://dx.doi.org/10.1093/hmg/ddh152
3. ↑ Taranta A, Petrini S, Palma A, Mannucci L, Wilmer MJ, De Luca V, Diomedi-Camassei F, Corallini S, Bellomo F, van den Heuvel LP, Levtchenko EN, Emma F. Identification and subcellular localization of a new cystinosin isoform. Am J Physiol Renal Physiol. 2008 May;294(5):F1101-8. doi:, 10.1152/ajprenal.00413.2007. Epub 2008 Mar 12. PMID:18337546 doi:http://dx.doi.org/10.1152/ajprenal.00413.2007
4. ↑ Ruivo R, Bellenchi GC, Chen X, Zifarelli G, Sagne C, Debacker C, Pusch M, Supplisson S, Gasnier B. Mechanism of proton/substrate coupling in the heptahelical lysosomal transporter cystinosin. Proc Natl Acad Sci U S A. 2012 Jan 31;109(5):E210-7. doi:, 10.1073/pnas.1115581109. Epub 2012 Jan 9. PMID:22232659 doi:http://dx.doi.org/10.1073/pnas.1115581109
5. ↑ Chiaverini C, Sillard L, Flori E, Ito S, Briganti S, Wakamatsu K, Fontas E, Berard E, Cailliez M, Cochat P, Foulard M, Guest G, Niaudet P, Picardo M, Bernard FX, Antignac C, Ortonne JP, Ballotti R. Cystinosin is a melanosomal protein that regulates melanin synthesis. FASEB J. 2012 Sep;26(9):3779-89. doi: 10.1096/fj.11-201376. Epub 2012 May 30. PMID:22649030 doi:http://dx.doi.org/10.1096/fj.11-201376
6. ↑ Deshpande AA, Shukla A, Bachhawat AK. A Genetic Screen for Investigating the Human Lysosomal CystineTransporter, Cystinosin. Sci Rep. 2018 Feb 21;8(1):3442. doi: 10.1038/s41598-018-21483-x. PMID:29467429 doi:http://dx.doi.org/10.1038/s41598-018-21483-x
7. ↑ Adelmann CH, Traunbauer AK, Chen B, Condon KJ, Chan SH, Kunchok T, Lewis CA, Sabatini DM. MFSD12 mediates the import of cysteine into melanosomes and lysosomes. Nature. 2020 Dec;588(7839):699-704. doi: 10.1038/s41586-020-2937-x. Epub 2020 Nov, 18. PMID:33208952 doi:http://dx.doi.org/10.1038/s41586-020-2937-x