CTNS_HUMAN
ID CTNS_HUMAN Reviewed; 367 AA.
AC O60931; D3DTJ5; Q8IZ01; Q9UNK6;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Cystinosin {ECO:0000303|PubMed:9537412};
DE Flags: Precursor;
GN Name=CTNS {ECO:0000303|PubMed:9537412, ECO:0000312|HGNC:HGNC:2518};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND VARIANT ILE-260.
RC TISSUE=Kidney;
RX PubMed=9537412; DOI=10.1038/ng0498-319;
RA Town M., Jean G., Cherqui S., Attard M., Forestier L., Whitmore S.A.,
RA Callen D.F., Gribouval O., Broyer M., Bates G.P., van 't Hoff W.,
RA Antignac C.;
RT "A novel gene encoding an integral membrane protein is mutated in
RT nephropathic cystinosis.";
RL Nat. Genet. 18:319-324(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ILE-260.
RX PubMed=10673275; DOI=10.1101/gr.10.2.165;
RA Touchman J.W., Anikster Y., Dietrich N.L., Maduro V.V.B., McDowell G.,
RA Shotelersuk V., Bouffard G.G., Beckstrom-Sternberg S.M., Gahl W.A.,
RA Green E.D.;
RT "The genomic region encompassing the nephropathic cystinosis gene (CTNS):
RT complete sequencing of a 200-kb segment and discovery of a novel gene
RT within the common cystinosis-causing deletion.";
RL Genome Res. 10:165-173(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT ILE-260.
RC TISSUE=Spleen;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ILE-260.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT ILE-260.
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 228-367, AND VARIANT ILE-260.
RX PubMed=10068513; DOI=10.1006/mgme.1998.2790;
RA Anikster Y., Lucero C., Touchman J.W., Huizing M., McDowell G.,
RA Shotelersuk V., Green E.D., Gahl W.A.;
RT "Identification and detection of the common 65-kb deletion breakpoint in
RT the nephropathic cystinosis gene (CTNS).";
RL Mol. Genet. Metab. 66:111-116(1999).
RN [8]
RP PROTEIN SEQUENCE OF 23-33, SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-36;
RP ASN-41; ASN-51; ASN-66; ASN-84; ASN-104 AND ASN-107, CHARACTERIZATION OF
RP VARIANT CTNSJAN 67-ILE--PRO-73 DEL, AND MUTAGENESIS OF ASN-66.
RX PubMed=28082515; DOI=10.1074/mcp.m116.063867;
RA Nevo N., Thomas L., Chhuon C., Andrzejewska Z., Lipecka J., Guillonneau F.,
RA Bailleux A., Edelman A., Antignac C., Guerrera I.C.;
RT "Impact of cystinosin glycosylation on protein stability by differential
RT dynamic stable isotope labeling by amino acids in cell culture (SILAC).";
RL Mol. Cell. Proteomics 16:457-468(2017).
RN [9]
RP REVIEW ON VARIANTS CYSTINOSIS.
RX PubMed=10571941;
RX DOI=10.1002/(sici)1098-1004(199912)14:6<454::aid-humu2>3.0.co;2-h;
RA Anikster Y., Shotelersuk V., Gahl W.A.;
RT "CTNS mutations in patients with cystinosis.";
RL Hum. Mutat. 14:454-458(1999).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, AND CHARACTERIZATION OF VARIANT CTNS ARG-308.
RX PubMed=11689434; DOI=10.1093/emboj/20.21.5940;
RA Kalatzis V., Cherqui S., Antignac C., Gasnier B.;
RT "Cystinosin, the protein defective in cystinosis, is a H(+)-driven
RT lysosomal cystine transporter.";
RL EMBO J. 20:5940-5949(2001).
RN [11]
RP SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF 280-LYS--ASN-288;
RP 281-TYR--GLN-284; 286-TYR--PHE-289; 289-PHE--SER-298; 362-GLY--LEU-366;
RP GLY-362; TYR-363; ASP-364; GLN-365 AND LEU-366.
RX PubMed=11150305; DOI=10.1074/jbc.m010562200;
RA Cherqui S., Kalatzis V., Trugnan G., Antignac C.;
RT "The targeting of cystinosin to the lysosomal membrane requires a tyrosine-
RT based signal and a novel sorting motif.";
RL J. Biol. Chem. 276:13314-13321(2001).
RN [12]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Placenta;
RX PubMed=17897319; DOI=10.1111/j.1600-0854.2007.00643.x;
RA Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H.,
RA Elsaesser H.-P., Mann M., Hasilik A.;
RT "Integral and associated lysosomal membrane proteins.";
RL Traffic 8:1676-1686(2007).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION (ISOFORM 2), CATALYTIC ACTIVITY (ISOFORM 2),
RP AND ALTERNATIVE SPLICING.
RX PubMed=18337546; DOI=10.1152/ajprenal.00413.2007;
RA Taranta A., Petrini S., Palma A., Mannucci L., Wilmer M.J., De Luca V.,
RA Diomedi-Camassei F., Corallini S., Bellomo F., van den Heuvel L.P.,
RA Levtchenko E.N., Emma F.;
RT "Identification and subcellular localization of a new cystinosin isoform.";
RL Am. J. Physiol. 294:F1101-F1108(2008).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22649030; DOI=10.1096/fj.11-201376;
RA Chiaverini C., Sillard L., Flori E., Ito S., Briganti S., Wakamatsu K.,
RA Fontas E., Berard E., Cailliez M., Cochat P., Foulard M., Guest G.,
RA Niaudet P., Picardo M., Bernard F.X., Antignac C., Ortonne J.P.,
RA Ballotti R.;
RT "Cystinosin is a melanosomal protein that regulates melanin synthesis.";
RL FASEB J. 26:3779-3789(2012).
RN [15]
RP TISSUE SPECIFICITY (ISOFORMS 1 AND 2).
RX PubMed=22544350; DOI=10.1007/s00418-012-0958-8;
RA Taranta A., Petrini S., Citti A., Boldrini R., Corallini S., Bellomo F.,
RA Levtchenko E., Emma F.;
RT "Distribution of cystinosin-LKG in human tissues.";
RL Histochem. Cell Biol. 138:351-363(2012).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SITE,
RP CHARACTERIZATION OF VARIANT CTNS ARG-308, AND MUTAGENESIS OF TYR-143;
RP ARG-152; ASP-161; ASP-205; HIS-211; TYR-281; ASP-305 AND LYS-335.
RX PubMed=22232659; DOI=10.1073/pnas.1115581109;
RA Ruivo R., Bellenchi G.C., Chen X., Zifarelli G., Sagne C., Debacker C.,
RA Pusch M., Supplisson S., Gasnier B.;
RT "Mechanism of proton/substrate coupling in the heptahelical lysosomal
RT transporter cystinosin.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:E210-E217(2012).
RN [17]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH AP-3 COMPLEX (ISOFORM 1).
RX PubMed=25753619; DOI=10.1111/tra.12277;
RA Andrzejewska Z., Nevo N., Thomas L., Bailleux A., Chauvet V., Benmerah A.,
RA Antignac C.;
RT "Lysosomal targeting of cystinosin requires AP-3.";
RL Traffic 16:712-726(2015).
RN [18]
RP SUBCELLULAR LOCATION (ISOFORM 2).
RX PubMed=27148969; DOI=10.1371/journal.pone.0154805;
RA Bellomo F., Taranta A., Petrini S., Venditti R., Rocchetti M.T., Rega L.R.,
RA Corallini S., Gesualdo L., De Matteis M.A., Emma F.;
RT "Carboxyl-terminal SSLKG motif of the human cystinosin-LKG plays an
RT important role in plasma membrane sorting.";
RL PLoS ONE 11:e0154805-e0154805(2016).
RN [19]
RP FUNCTION, AND MUTAGENESIS OF GLY-131; ALA-137; SER-270; LEU-274; GLY-309;
RP SER-312; 362-GLY--LEU-366; TYR-363 AND LEU-366.
RX PubMed=29467429; DOI=10.1038/s41598-018-21483-x;
RA Deshpande A.A., Shukla A., Bachhawat A.K.;
RT "A genetic screen for investigating the human lysosomal cystine
RT transporter, cystinosin.";
RL Sci. Rep. 8:3442-3442(2018).
RN [20]
RP FUNCTION.
RX PubMed=33208952; DOI=10.1038/s41586-020-2937-x;
RA Adelmann C.H., Traunbauer A.K., Chen B., Condon K.J., Chan S.H.,
RA Kunchok T., Lewis C.A., Sabatini D.M.;
RT "MFSD12 mediates the import of cysteine into melanosomes and lysosomes.";
RL Nature 588:699-704(2020).
RN [21]
RP VARIANTS CTNS ASP-169; ARG-182; ASN-205; ASP-205 DEL; ASN-298; GLY-305;
RP ARG-308 AND ARG-339, VARIANT CTNSJAN 67-ILE--PRO-73 DEL, AND VARIANT
RP ARG-292.
RX PubMed=9792862; DOI=10.1086/302118;
RA Shotelersuk V., Larson D., Anikster Y., McDowell G., Lemons R.,
RA Bernardini I., Guo J., Thoene J., Gahl W.A.;
RT "CTNS mutations in an American-based population of cystinosis patients.";
RL Am. J. Hum. Genet. 63:1352-1362(1998).
RN [22]
RP VARIANTS CTNS PHE-133 AND PRO-158.
RX PubMed=10482956; DOI=10.1038/sj.ejhg.5200349;
RA McGowan-Jordan J., Stoddard K., Podolsky L., Orrbine E., McLaine P.,
RA Town M., Goodyer P., MacKenzie A., Heick H.;
RT "Molecular analysis of cystinosis: probable Irish origin of the most common
RT French Canadian mutation.";
RL Eur. J. Hum. Genet. 7:671-678(1999).
RN [23]
RP VARIANTS CTNSJAN ARG-280 AND LYS-323.
RX PubMed=10444339; DOI=10.1006/mgme.1999.2876;
RA Thoene J., Lemons R., Anikster Y., Mullet J., Paelicke K., Lucero C.,
RA Gahl W.A., Schneider J., Shu S.G., Campbell H.T.;
RT "Mutations of CTNS causing intermediate cystinosis.";
RL Mol. Genet. Metab. 67:283-293(1999).
RN [24]
RP VARIANTS CTNS PHE-139; ASP-205 DEL; SER-270 DEL; TYR-305; ARG-308; PRO-338;
RP ARG-339; 343-ILE--ASP-346 DEL AND ASN-346, VARIANT ILE-42, AND VARIANT
RP CTNSJAN PRO-CYS-SER-154 INS.
RX PubMed=10556299; DOI=10.1093/hmg/8.13.2507;
RA Attard M., Jean G., Forestier L., Cherqui S., van 't Hoff W., Broyer M.,
RA Antignac C., Town M.;
RT "Severity of phenotype in cystinosis varies with mutations in the CTNS
RT gene: predicted effect on the model of cystinosin.";
RL Hum. Mol. Genet. 8:2507-2514(1999).
RN [25]
RP VARIANT CTNSANN ARG-197.
RX PubMed=10625078; DOI=10.1203/00006450-200001000-00007;
RA Anikster Y., Lucero C., Guo J., Huizing M., Shotelersuk V., Bernardini I.,
RA McDowell G., Iwata F., Kaiser-Kupfer M.I., Jaffe R., Thoene J.,
RA Schneider J.A., Gahl W.A.;
RT "Ocular nonnephropathic cystinosis: clinical, biochemical, and molecular
RT correlations.";
RL Pediatr. Res. 47:17-23(2000).
RN [26]
RP VARIANTS CTNS VAL-308 AND ARG-339.
RX PubMed=12204010; DOI=10.1002/humu.9063;
RA Kiehntopf M., Schickel J., Gonne B., Koch H.G., Superti-Furga A.,
RA Steinmann B., Deufel T., Harms E.;
RT "Analysis of the CTNS gene in patients of German and Swiss origin with
RT nephropathic cystinosis.";
RL Hum. Mutat. 20:237-237(2002).
RN [27]
RP VARIANTS CTNS VAL-110; ARG-222; LYS-288; ASP-346--349-PHE DEL AND
RP ASP-VAL-GLU-PHE-349 INS, AND VARIANTS CTNSJAN THR-177 AND LEU-200.
RX PubMed=12442267; DOI=10.1002/humu.10141;
RA Kalatzis V., Cohen-Solal L., Cordier B., Frishberg Y., Kemper M.,
RA Nuutinen E.M., Legrand E., Cochat P., Antignac C.;
RT "Identification of 14 novel CTNS mutations and characterization of seven
RT splice site mutations associated with cystinosis.";
RL Hum. Mutat. 20:439-446(2002).
RN [28]
RP VARIANTS CTNS ILE-287; ARG-308; ARG-337 AND ARG-339, AND VARIANT ILE-260.
RX PubMed=12825071; DOI=10.1038/sj.ejhg.5200993;
RA Mason S., Pepe G., Dall'Amico R., Tartaglia S., Casciani S., Greco M.,
RA Bencivenga P., Murer L., Rizzoni G., Tenconi R., Clementi M.;
RT "Mutational spectrum of the CTNS gene in Italy.";
RL Eur. J. Hum. Genet. 11:503-508(2003).
RN [29]
RP FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS CTNS VAL-110;
RP PHE-133; PHE-139; PHE-141; PRO-158; ASP-169; SER-177; ARG-182; ASN-205;
RP ASP-205 DEL; ARG-222; SER-270 DEL; LYS-288; ASN-298; TYR-305; ARG-308;
RP PRO-338; ARG-339; 343-ILE--ASP-346 DEL; ASP-346--349-PHE DEL AND
RP ASP-VAL-GLU-PHE-349 INS, CHARACTERIZATION OF VARIANT CTNSJAN 67-ILE--PRO-73
RP DEL; PRO-CYS-SER-154 INS; LEU-200; ARG-280; LYS-323 AND ASN-346,
RP CHARACTERIZATION OF VARIANT CTNSANN ARG-197, AND CHARACTERIZATION OF
RP VARIANT ILE-42 AND ILE-260.
RX PubMed=15128704; DOI=10.1093/hmg/ddh152;
RA Kalatzis V., Nevo N., Cherqui S., Gasnier B., Antignac C.;
RT "Molecular pathogenesis of cystinosis: effect of CTNS mutations on the
RT transport activity and subcellular localization of cystinosin.";
RL Hum. Mol. Genet. 13:1361-1371(2004).
RN [30]
RP VARIANTS CTNS SER-177 AND ARG-338.
RX PubMed=19852576; DOI=10.3109/13816810903200953;
RA Aldahmesh M.A., Humeidan A., Almojalli H.A., Khan A.O., Rajab M.,
RA Al-Abbad A.A., Meyer B.F., Alkuraya F.S.;
RT "Characterization of CTNS mutations in Arab patients with cystinosis.";
RL Ophthalmic Genet. 30:185-189(2009).
RN [31]
RP VARIANTS CTNS ASP-309 AND LYS-323.
RX PubMed=22450360; DOI=10.1016/j.gene.2012.03.047;
RA Yeetong P., Tongkobpetch S., Kingwatanakul P., Deekajorndech T.,
RA Bernardini I.M., Suphapeetiporn K., Gahl W.A., Shotelersuk V.;
RT "Two novel CTNS mutations in cystinosis patients in Thailand.";
RL Gene 499:323-325(2012).
RN [32]
RP VARIANTS CTNS GLY-151; ASP-157 AND CYS-173.
RX PubMed=21786142; DOI=10.1007/s00467-011-1942-6;
RA Topaloglu R., Vilboux T., Coskun T., Ozaltin F., Tinloy B., Gunay-Aygun M.,
RA Bakkaloglu A., Besbas N., van den Heuvel L., Kleta R., Gahl W.A.;
RT "Genetic basis of cystinosis in Turkish patients: a single-center
RT experience.";
RL Pediatr. Nephrol. 27:115-121(2012).
CC -!- FUNCTION: Cystine/H(+) symporter that mediates export of cystine, the
CC oxidized dimer of cysteine, from lysosomes (PubMed:11689434,
CC PubMed:18337546, PubMed:22232659, PubMed:29467429, PubMed:33208952,
CC PubMed:15128704). Plays an important role in melanin synthesis by
CC catalyzing cystine export from melanosomes, possibly by inhibiting
CC pheomelanin synthesis (PubMed:22649030). In addition to cystine export,
CC also acts as a positive regulator of mTORC1 signaling in kidney
CC proximal tubular cells, via interactions with components of the v-
CC ATPase and Ragulator complexes (By similarity). Also involved in small
CC GTPase-regulated vesicle trafficking and lysosomal localization of
CC LAMP2A, independently of cystine transporter activity (By similarity).
CC {ECO:0000250|UniProtKB:P57757, ECO:0000269|PubMed:11689434,
CC ECO:0000269|PubMed:15128704, ECO:0000269|PubMed:18337546,
CC ECO:0000269|PubMed:22232659, ECO:0000269|PubMed:22649030,
CC ECO:0000269|PubMed:29467429, ECO:0000269|PubMed:33208952}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(out) + L-cystine(out) = H(+)(in) + L-cystine(in);
CC Xref=Rhea:RHEA:66172, ChEBI:CHEBI:15378, ChEBI:CHEBI:35491;
CC Evidence={ECO:0000269|PubMed:11689434, ECO:0000269|PubMed:22232659};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66173;
CC Evidence={ECO:0000269|PubMed:11689434, ECO:0000269|PubMed:22232659};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=H(+)(out) + L-cystine(out) = H(+)(in) + L-cystine(in);
CC Xref=Rhea:RHEA:66172, ChEBI:CHEBI:15378, ChEBI:CHEBI:35491;
CC Evidence={ECO:0000269|PubMed:18337546};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66173;
CC Evidence={ECO:0000269|PubMed:18337546};
CC -!- CATALYTIC ACTIVITY: [Isoform 2]:
CC Reaction=H(+)(out) + L-cystine(out) = H(+)(in) + L-cystine(in);
CC Xref=Rhea:RHEA:66172, ChEBI:CHEBI:15378, ChEBI:CHEBI:35491;
CC Evidence={ECO:0000269|PubMed:18337546};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66173;
CC Evidence={ECO:0000269|PubMed:18337546};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=75 uM for cystine (at pH 5.0) {ECO:0000269|PubMed:22232659};
CC KM=278 uM for cystine {ECO:0000269|PubMed:11689434};
CC -!- SUBUNIT: Interacts with components of the V-ATPase complex. Interacts
CC with components of the Ragulator complex. Interacts with RRAGA/RagA and
CC RRAGC/RagC (By similarity). Interacts with AP-3 complex subunit mu
CC (AP3M1 or AP3M2) (PubMed:25753619). {ECO:0000250|UniProtKB:P57757,
CC ECO:0000269|PubMed:25753619}.
CC -!- INTERACTION:
CC O60931-2; Q14749: GNMT; NbExp=3; IntAct=EBI-19888994, EBI-744239;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Lysosome membrane
CC {ECO:0000269|PubMed:11150305, ECO:0000269|PubMed:11689434,
CC ECO:0000269|PubMed:15128704, ECO:0000269|PubMed:17897319,
CC ECO:0000269|PubMed:25753619, ECO:0000269|PubMed:28082515}; Multi-pass
CC membrane protein {ECO:0000255}. Melanosome membrane
CC {ECO:0000269|PubMed:22649030}; Multi-pass membrane protein
CC {ECO:0000255}. Note=AP-3 complex is required for localization to the
CC lysosome. {ECO:0000269|PubMed:25753619}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Lysosome membrane
CC {ECO:0000269|PubMed:18337546, ECO:0000269|PubMed:27148969}; Multi-pass
CC membrane protein {ECO:0000255}. Cell membrane
CC {ECO:0000269|PubMed:18337546, ECO:0000269|PubMed:27148969}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O60931-1; Sequence=Displayed;
CC Name=2; Synonyms=cystinosin-LKG {ECO:0000303|PubMed:22544350};
CC IsoId=O60931-2; Sequence=VSP_038377;
CC -!- TISSUE SPECIFICITY: Strongly expressed in pancreas, kidney (adult and
CC fetal), skeletal muscle, melanocytes and keratinocytes
CC (PubMed:22649030). Expressed at lower levels in placenta and heart.
CC Weakly expressed in lung, liver and brain (adult and fetal)
CC (PubMed:22649030). {ECO:0000269|PubMed:22649030}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Represents 5-20 % of CTNS transcripts,
CC with the exception of the testis that expresses both isoforms in equal
CC proportions. {ECO:0000269|PubMed:22649030}.
CC -!- DOMAIN: The lysosomal targeting motif, together with the second PQ-loop
CC mediate targeting to the lysosome. {ECO:0000269|PubMed:11150305}.
CC -!- DISEASE: Cystinosis, nephropathic type (CTNS) [MIM:219800]: A form of
CC cystinosis, a lysosomal storage disease due to defective transport of
CC cystine across the lysosomal membrane. This results in cystine
CC accumulation and crystallization in the cells causing widespread tissue
CC damage. The classical nephropathic form has onset in the first year of
CC life and is characterized by a polyuro-polydipsic syndrome, marked
CC height-weight growth delay, generalized impaired proximal tubular
CC reabsorptive capacity, with severe fluid-electrolyte balance
CC alterations, renal failure, ocular symptoms and other systemic
CC complications. {ECO:0000269|PubMed:10482956,
CC ECO:0000269|PubMed:10556299, ECO:0000269|PubMed:11689434,
CC ECO:0000269|PubMed:12204010, ECO:0000269|PubMed:12442267,
CC ECO:0000269|PubMed:12825071, ECO:0000269|PubMed:15128704,
CC ECO:0000269|PubMed:19852576, ECO:0000269|PubMed:21786142,
CC ECO:0000269|PubMed:22232659, ECO:0000269|PubMed:22450360,
CC ECO:0000269|PubMed:9792862}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Cystinosis, adult, non-nephropathic type (CTNSANN)
CC [MIM:219750]: A form of cystinosis, a lysosomal storage disease due to
CC defective transport of cystine across the lysosomal membrane. This
CC results in cystine accumulation and crystallization in the cells
CC causing widespread tissue damage. Cystinosis adult non-nephropathic
CC type is characterized by ocular features and a benign course. Patients
CC manifest mild photophobia due to conjunctival and corneal cystine
CC crystals. {ECO:0000269|PubMed:10625078, ECO:0000269|PubMed:15128704}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Cystinosis, late-onset juvenile or adolescent nephropathic
CC type (CTNSJAN) [MIM:219900]: A form of cystinosis, a lysosomal storage
CC disease due to defective transport of cystine across the lysosomal
CC membrane. This results in cystine accumulation and crystallization in
CC the cells causing widespread tissue damage. Late-onset juvenile or
CC adolescent nephropathic cystinosis is an intermediated form,
CC manifesting first at age 10 to 12 years with proteinuria due to
CC glomerular damage rather than with the manifestations of tubular damage
CC that occur first in infantile cystinosis. There is no excess amino
CC aciduria and stature is normal. Photophobia, late development of
CC pigmentary retinopathy, and chronic headaches are features.
CC {ECO:0000269|PubMed:10444339, ECO:0000269|PubMed:10556299,
CC ECO:0000269|PubMed:12442267, ECO:0000269|PubMed:15128704,
CC ECO:0000269|PubMed:28082515, ECO:0000269|PubMed:9792862}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the cystinosin family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; Y15924; CAA75882.1; -; Genomic_DNA.
DR EMBL; Y15925; CAA75882.1; JOINED; Genomic_DNA.
DR EMBL; Y15926; CAA75882.1; JOINED; Genomic_DNA.
DR EMBL; Y15927; CAA75882.1; JOINED; Genomic_DNA.
DR EMBL; Y15928; CAA75882.1; JOINED; Genomic_DNA.
DR EMBL; Y15929; CAA75882.1; JOINED; Genomic_DNA.
DR EMBL; Y15930; CAA75882.1; JOINED; Genomic_DNA.
DR EMBL; Y15931; CAA75882.1; JOINED; Genomic_DNA.
DR EMBL; Y15932; CAA75882.1; JOINED; Genomic_DNA.
DR EMBL; Y15933; CAA75882.1; JOINED; Genomic_DNA.
DR EMBL; AJ222967; CAA11021.1; -; mRNA.
DR EMBL; AF168787; AAF43102.1; -; Genomic_DNA.
DR EMBL; AK292019; BAF84708.1; -; mRNA.
DR EMBL; AC027796; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC132942; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471108; EAW90495.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90494.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90496.1; -; Genomic_DNA.
DR EMBL; BC032850; AAH32850.1; -; mRNA.
DR EMBL; AH008011; AAD45630.1; -; Genomic_DNA.
DR CCDS; CCDS11031.1; -. [O60931-1]
DR CCDS; CCDS32530.1; -. [O60931-2]
DR RefSeq; NP_001026851.2; NM_001031681.2. [O60931-2]
DR RefSeq; NP_004928.2; NM_004937.2. [O60931-1]
DR AlphaFoldDB; O60931; -.
DR BioGRID; 107878; 3.
DR IntAct; O60931; 1.
DR STRING; 9606.ENSP00000371294; -.
DR ChEMBL; CHEMBL4630803; -.
DR DrugBank; DB00138; Cystine.
DR TCDB; 2.A.43.1.1; the lysosomal cystine transporter (lct) family.
DR GlyGen; O60931; 7 sites.
DR iPTMnet; O60931; -.
DR PhosphoSitePlus; O60931; -.
DR BioMuta; CTNS; -.
DR jPOST; O60931; -.
DR MassIVE; O60931; -.
DR MaxQB; O60931; -.
DR PaxDb; O60931; -.
DR PeptideAtlas; O60931; -.
DR PRIDE; O60931; -.
DR ProteomicsDB; 49677; -. [O60931-2]
DR Antibodypedia; 23081; 199 antibodies from 27 providers.
DR DNASU; 1497; -.
DR Ensembl; ENST00000046640.9; ENSP00000046640.4; ENSG00000040531.16. [O60931-1]
DR Ensembl; ENST00000381870.8; ENSP00000371294.3; ENSG00000040531.16. [O60931-2]
DR Ensembl; ENST00000673965.1; ENSP00000500995.1; ENSG00000040531.16. [O60931-1]
DR GeneID; 1497; -.
DR KEGG; hsa:1497; -.
DR MANE-Select; ENST00000046640.9; ENSP00000046640.4; NM_004937.3; NP_004928.2.
DR UCSC; uc002fwa.4; human. [O60931-1]
DR CTD; 1497; -.
DR DisGeNET; 1497; -.
DR GeneCards; CTNS; -.
DR GeneReviews; CTNS; -.
DR HGNC; HGNC:2518; CTNS.
DR HPA; ENSG00000040531; Low tissue specificity.
DR MalaCards; CTNS; -.
DR MIM; 219750; phenotype.
DR MIM; 219800; phenotype.
DR MIM; 219900; phenotype.
DR MIM; 606272; gene.
DR neXtProt; NX_O60931; -.
DR OpenTargets; ENSG00000040531; -.
DR Orphanet; 411629; Infantile nephropathic cystinosis.
DR Orphanet; 411634; Juvenile nephropathic cystinosis.
DR Orphanet; 411641; Ocular cystinosis.
DR PharmGKB; PA27019; -.
DR VEuPathDB; HostDB:ENSG00000040531; -.
DR eggNOG; KOG3145; Eukaryota.
DR GeneTree; ENSGT00390000005338; -.
DR HOGENOM; CLU_046327_1_0_1; -.
DR InParanoid; O60931; -.
DR OMA; WIDVIYT; -.
DR PhylomeDB; O60931; -.
DR TreeFam; TF313589; -.
DR PathwayCommons; O60931; -.
DR Reactome; R-HSA-425393; Transport of inorganic cations/anions and amino acids/oligopeptides.
DR Reactome; R-HSA-5223345; Miscellaneous transport and binding events.
DR SignaLink; O60931; -.
DR BioGRID-ORCS; 1497; 17 hits in 1075 CRISPR screens.
DR ChiTaRS; CTNS; human.
DR GeneWiki; CTNS_(gene); -.
DR GenomeRNAi; 1497; -.
DR Pharos; O60931; Tbio.
DR PRO; PR:O60931; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; O60931; protein.
DR Bgee; ENSG00000040531; Expressed in right adrenal gland cortex and 167 other tissues.
DR ExpressionAtlas; O60931; baseline and differential.
DR Genevisible; O60931; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:MGI.
DR GO; GO:0042470; C:melanosome; IDA:UniProtKB.
DR GO; GO:0033162; C:melanosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005774; C:vacuolar membrane; IBA:GO_Central.
DR GO; GO:0015184; F:L-cystine transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015295; F:solute:proton symporter activity; IDA:UniProtKB.
DR GO; GO:0007628; P:adult walking behavior; IEA:Ensembl.
DR GO; GO:0046034; P:ATP metabolic process; IMP:UniProtKB.
DR GO; GO:0007420; P:brain development; IMP:UniProtKB.
DR GO; GO:0006520; P:cellular amino acid metabolic process; NAS:UniProtKB.
DR GO; GO:0050890; P:cognition; IMP:UniProtKB.
DR GO; GO:0006749; P:glutathione metabolic process; IMP:UniProtKB.
DR GO; GO:0007625; P:grooming behavior; IEA:Ensembl.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0015811; P:L-cystine transport; IDA:UniProtKB.
DR GO; GO:0002088; P:lens development in camera-type eye; IEA:Ensembl.
DR GO; GO:0007616; P:long-term memory; IEA:Ensembl.
DR GO; GO:0042438; P:melanin biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0010730; P:negative regulation of hydrogen peroxide biosynthetic process; IEA:Ensembl.
DR GO; GO:0010918; P:positive regulation of mitochondrial membrane potential; IEA:Ensembl.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; IEA:Ensembl.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0048021; P:regulation of melanin biosynthetic process; IMP:UniProtKB.
DR GO; GO:0055085; P:transmembrane transport; TAS:Reactome.
DR GO; GO:0008542; P:visual learning; IEA:Ensembl.
DR InterPro; IPR005282; LC_transporter.
DR InterPro; IPR006603; PQ-loop_rpt.
DR PANTHER; PTHR13131; PTHR13131; 1.
DR Pfam; PF04193; PQ-loop; 2.
DR SMART; SM00679; CTNS; 2.
DR TIGRFAMs; TIGR00951; 2A43; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Direct protein sequencing;
KW Disease variant; Glycoprotein; Lysosome; Melanin biosynthesis; Membrane;
KW Protein transport; Reference proteome; Repeat; Signal; Symport;
KW Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:28082515"
FT CHAIN 23..367
FT /note="Cystinosin"
FT /id="PRO_0000205514"
FT TOPO_DOM 23..121
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 122..142
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 143..161
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 162..182
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 183..205
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 206..226
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 227..237
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 238..258
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 259..261
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 262..282
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 283..297
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 298..318
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 319..335
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 336..356
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 357..367
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 123..189
FT /note="PQ-loop 1"
FT /evidence="ECO:0000255"
FT DOMAIN 263..328
FT /note="PQ-loop 2"
FT /evidence="ECO:0000255"
FT MOTIF 362..366
FT /note="Lysosomal targeting motif"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:11150305"
FT BINDING 305
FT /ligand="H(+)"
FT /ligand_id="ChEBI:CHEBI:15378"
FT /note="protonated residue following cystine-binding"
FT /evidence="ECO:0000269|PubMed:22232659"
FT CARBOHYD 36
FT /note="N-linked (GlcNAc...) (high mannose) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:28082515"
FT CARBOHYD 41
FT /note="N-linked (GlcNAc...) (high mannose) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:28082515"
FT CARBOHYD 51
FT /note="N-linked (GlcNAc...) (high mannose) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:28082515"
FT CARBOHYD 66
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:28082515"
FT CARBOHYD 84
FT /note="N-linked (GlcNAc...) (high mannose) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:28082515"
FT CARBOHYD 104
FT /note="N-linked (GlcNAc...) (high mannose) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:28082515"
FT CARBOHYD 107
FT /note="N-linked (GlcNAc...) (high mannose) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:28082515"
FT VAR_SEQ 363..367
FT /note="YDQLN -> LQAARTGSGSRLRQDWAPSLQPKALPQTTSVSASSLKG (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_038377"
FT VARIANT 42
FT /note="V -> I (does not affect cystine transport;
FT dbSNP:rs35086888)"
FT /evidence="ECO:0000269|PubMed:10556299,
FT ECO:0000269|PubMed:15128704"
FT /id="VAR_010285"
FT VARIANT 67..73
FT /note="Missing (in CTNSJAN; protein misfolding leading to
FT decreased stability; decreased cystine transport)"
FT /evidence="ECO:0000269|PubMed:15128704,
FT ECO:0000269|PubMed:28082515, ECO:0000269|PubMed:9792862"
FT /id="VAR_010674"
FT VARIANT 110
FT /note="G -> V (in CTNS; atypical; does not affect cystine
FT transport; dbSNP:rs121908129)"
FT /evidence="ECO:0000269|PubMed:12442267,
FT ECO:0000269|PubMed:15128704"
FT /id="VAR_037318"
FT VARIANT 133
FT /note="I -> F (in CTNS; does not affect cystine transport;
FT dbSNP:rs886040970)"
FT /evidence="ECO:0000269|PubMed:10482956,
FT ECO:0000269|PubMed:15128704"
FT /id="VAR_010677"
FT VARIANT 139
FT /note="S -> F (in CTNS; atypical; abolished cystine
FT transport; dbSNP:rs267606754)"
FT /evidence="ECO:0000269|PubMed:10556299,
FT ECO:0000269|PubMed:15128704"
FT /id="VAR_010678"
FT VARIANT 141
FT /note="S -> F (in CTNS; abolished cystine transport)"
FT /evidence="ECO:0000269|PubMed:15128704"
FT /id="VAR_084186"
FT VARIANT 151
FT /note="R -> G (in CTNS; dbSNP:rs1555563010)"
FT /evidence="ECO:0000269|PubMed:21786142"
FT /id="VAR_067490"
FT VARIANT 154
FT /note="S -> SPCS (in CTNSJAN; decreased cystine transport)"
FT /evidence="ECO:0000269|PubMed:10556299,
FT ECO:0000269|PubMed:15128704"
FT /id="VAR_010679"
FT VARIANT 157
FT /note="G -> D (in CTNS)"
FT /evidence="ECO:0000269|PubMed:21786142"
FT /id="VAR_067491"
FT VARIANT 158
FT /note="L -> P (in CTNS; abolished cystine transport;
FT dbSNP:rs113994206)"
FT /evidence="ECO:0000269|PubMed:10482956,
FT ECO:0000269|PubMed:15128704"
FT /id="VAR_010680"
FT VARIANT 169
FT /note="G -> D (in CTNS; abolished cystine transport;
FT dbSNP:rs121908126)"
FT /evidence="ECO:0000269|PubMed:15128704,
FT ECO:0000269|PubMed:9792862"
FT /id="VAR_010286"
FT VARIANT 173
FT /note="Y -> C (in CTNS; dbSNP:rs1555563446)"
FT /evidence="ECO:0000269|PubMed:21786142"
FT /id="VAR_067492"
FT VARIANT 177
FT /note="N -> S (in CTNS; abolished cystine transport)"
FT /evidence="ECO:0000269|PubMed:15128704,
FT ECO:0000269|PubMed:19852576"
FT /id="VAR_067493"
FT VARIANT 177
FT /note="N -> T (in CTNSJAN)"
FT /evidence="ECO:0000269|PubMed:12442267"
FT /id="VAR_037319"
FT VARIANT 182
FT /note="W -> R (in CTNS; does not affect cystine transport;
FT dbSNP:rs764168489)"
FT /evidence="ECO:0000269|PubMed:15128704,
FT ECO:0000269|PubMed:9792862"
FT /id="VAR_010681"
FT VARIANT 197
FT /note="G -> R (in CTNSANN; decreased cystine transport;
FT dbSNP:rs113994207)"
FT /evidence="ECO:0000269|PubMed:10625078,
FT ECO:0000269|PubMed:15128704"
FT /id="VAR_010682"
FT VARIANT 200
FT /note="P -> L (in CTNSJAN; decreased cystine transport)"
FT /evidence="ECO:0000269|PubMed:12442267,
FT ECO:0000269|PubMed:15128704"
FT /id="VAR_037320"
FT VARIANT 205
FT /note="D -> N (in CTNS; abolished cystine transport;
FT dbSNP:rs113994208)"
FT /evidence="ECO:0000269|PubMed:15128704,
FT ECO:0000269|PubMed:9792862"
FT /id="VAR_010683"
FT VARIANT 205
FT /note="Missing (in CTNS; abolished cystine transport)"
FT /evidence="ECO:0000269|PubMed:10556299,
FT ECO:0000269|PubMed:15128704, ECO:0000269|PubMed:9792862"
FT /id="VAR_010684"
FT VARIANT 222
FT /note="Q -> R (in CTNS; partial relocation to the cell
FT membrane; abolished cystine transport; dbSNP:rs1327959008)"
FT /evidence="ECO:0000269|PubMed:12442267,
FT ECO:0000269|PubMed:15128704"
FT /id="VAR_037321"
FT VARIANT 260
FT /note="T -> I (slightly decreased cystine transport;
FT dbSNP:rs161400)"
FT /evidence="ECO:0000269|PubMed:10068513,
FT ECO:0000269|PubMed:10673275, ECO:0000269|PubMed:12825071,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15128704,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9537412,
FT ECO:0000269|Ref.5"
FT /id="VAR_060371"
FT VARIANT 270
FT /note="Missing (in CTNS; abolished cystine transport)"
FT /evidence="ECO:0000269|PubMed:10556299,
FT ECO:0000269|PubMed:15128704"
FT /id="VAR_010689"
FT VARIANT 280
FT /note="K -> R (in CTNSJAN; abolished cystine transport)"
FT /evidence="ECO:0000269|PubMed:10444339,
FT ECO:0000269|PubMed:15128704"
FT /id="VAR_010287"
FT VARIANT 287
FT /note="M -> I (in CTNS; dbSNP:rs922106812)"
FT /evidence="ECO:0000269|PubMed:12825071"
FT /id="VAR_067494"
FT VARIANT 288
FT /note="N -> K (in CTNS; abolished cystine transport)"
FT /evidence="ECO:0000269|PubMed:12442267,
FT ECO:0000269|PubMed:15128704"
FT /id="VAR_037322"
FT VARIANT 292
FT /note="K -> R (found in patients with cystinosis; uncertain
FT pathological significance; dbSNP:rs1800527)"
FT /evidence="ECO:0000269|PubMed:9792862"
FT /id="VAR_012314"
FT VARIANT 298
FT /note="S -> N (in CTNS; does not affect cystine transport;
FT dbSNP:rs1212133760)"
FT /evidence="ECO:0000269|PubMed:15128704,
FT ECO:0000269|PubMed:9792862"
FT /id="VAR_012315"
FT VARIANT 305
FT /note="D -> G (in CTNS; dbSNP:rs1263951539)"
FT /evidence="ECO:0000269|PubMed:9792862"
FT /id="VAR_010690"
FT VARIANT 305
FT /note="D -> Y (in CTNS; abolished cystine transport)"
FT /evidence="ECO:0000269|PubMed:10556299,
FT ECO:0000269|PubMed:15128704"
FT /id="VAR_010691"
FT VARIANT 308
FT /note="G -> R (in CTNS; abolished cystine transport;
FT dbSNP:rs746307931)"
FT /evidence="ECO:0000269|PubMed:10556299,
FT ECO:0000269|PubMed:11689434, ECO:0000269|PubMed:12825071,
FT ECO:0000269|PubMed:15128704, ECO:0000269|PubMed:22232659,
FT ECO:0000269|PubMed:9792862"
FT /id="VAR_010692"
FT VARIANT 308
FT /note="G -> V (in CTNS; dbSNP:rs908965524)"
FT /evidence="ECO:0000269|PubMed:12204010"
FT /id="VAR_067495"
FT VARIANT 309
FT /note="G -> D (in CTNS)"
FT /evidence="ECO:0000269|PubMed:22450360"
FT /id="VAR_067496"
FT VARIANT 323
FT /note="N -> K (in CTNSJAN; abolished cystine transport;
FT dbSNP:rs121908128)"
FT /evidence="ECO:0000269|PubMed:10444339,
FT ECO:0000269|PubMed:15128704, ECO:0000269|PubMed:22450360"
FT /id="VAR_010288"
FT VARIANT 337
FT /note="G -> R (in CTNS)"
FT /evidence="ECO:0000269|PubMed:12825071"
FT /id="VAR_067497"
FT VARIANT 338
FT /note="L -> P (in CTNS; abolished cystine transport)"
FT /evidence="ECO:0000269|PubMed:10556299,
FT ECO:0000269|PubMed:15128704"
FT /id="VAR_010694"
FT VARIANT 338
FT /note="L -> R (in CTNS)"
FT /evidence="ECO:0000269|PubMed:19852576"
FT /id="VAR_067498"
FT VARIANT 339
FT /note="G -> R (in CTNS; abolished cystine transport;
FT dbSNP:rs121908127)"
FT /evidence="ECO:0000269|PubMed:10556299,
FT ECO:0000269|PubMed:12204010, ECO:0000269|PubMed:12825071,
FT ECO:0000269|PubMed:15128704, ECO:0000269|PubMed:9792862"
FT /id="VAR_010695"
FT VARIANT 343..346
FT /note="Missing (in CTNS; partial relocation to the cell
FT membrane; abolished cystine transport)"
FT /evidence="ECO:0000269|PubMed:10556299,
FT ECO:0000269|PubMed:15128704"
FT /id="VAR_010697"
FT VARIANT 346..349
FT /note="Missing (in CTNS; partial relocation to the cell
FT membrane; abolished cystine transport)"
FT /evidence="ECO:0000269|PubMed:12442267,
FT ECO:0000269|PubMed:15128704"
FT /id="VAR_037323"
FT VARIANT 346
FT /note="D -> N (in CTNS; atypical; slightly decreased
FT cystine transport; dbSNP:rs757535731)"
FT /evidence="ECO:0000269|PubMed:10556299,
FT ECO:0000269|PubMed:15128704"
FT /id="VAR_010698"
FT VARIANT 349
FT /note="F -> FDVEF (in CTNS; abolished cystine transport)"
FT /evidence="ECO:0000269|PubMed:12442267,
FT ECO:0000269|PubMed:15128704"
FT /id="VAR_037324"
FT MUTAGEN 66
FT /note="N->A: Decreased glycosylation."
FT /evidence="ECO:0000269|PubMed:28082515"
FT MUTAGEN 131
FT /note="G->S,D: Gain-of-function mutant that shows higher
FT transport of cystine."
FT /evidence="ECO:0000269|PubMed:29467429"
FT MUTAGEN 137
FT /note="A->V: Gain-of-function mutant that shows higher
FT transport of cystine."
FT /evidence="ECO:0000269|PubMed:29467429"
FT MUTAGEN 143
FT /note="Y->F: Slightly decreased midpoint potential.
FT Impaired dielectric distance."
FT /evidence="ECO:0000269|PubMed:22232659"
FT MUTAGEN 152
FT /note="R->Q: Impaired dielectric distance."
FT /evidence="ECO:0000269|PubMed:22232659"
FT MUTAGEN 161
FT /note="D->N: Strongly reduced steady-state transport
FT current. Slightly decreased midpoint potential."
FT /evidence="ECO:0000269|PubMed:22232659"
FT MUTAGEN 205
FT /note="D->N: Abolished steady-state transport current.
FT Decreased midpoint potential."
FT /evidence="ECO:0000269|PubMed:22232659"
FT MUTAGEN 211
FT /note="H->F: Accelerated the time course."
FT /evidence="ECO:0000269|PubMed:22232659"
FT MUTAGEN 270
FT /note="S->T: Gain-of-function mutant that shows higher
FT transport of cystine."
FT /evidence="ECO:0000269|PubMed:29467429"
FT MUTAGEN 274
FT /note="L->F: Gain-of-function mutant that shows higher
FT transport of cystine."
FT /evidence="ECO:0000269|PubMed:29467429"
FT MUTAGEN 280..288
FT /note="Missing: In delta(A) mutant; abolished localization
FT to the lysosome; when associated with deletion of 362-G--L-
FT 366."
FT /evidence="ECO:0000269|PubMed:11150305"
FT MUTAGEN 281..284
FT /note="YFPQ->AAAA: In mu(a) mutant; abolished localization
FT to the lysosome; when associated with deletion of 362-G--L-
FT 366."
FT /evidence="ECO:0000269|PubMed:11150305"
FT MUTAGEN 281
FT /note="Y->F: Decreased midpoint potential. Accelerated the
FT time course."
FT /evidence="ECO:0000269|PubMed:22232659"
FT MUTAGEN 286..289
FT /note="YMNF->AAAA: In mu(b) mutant; does not abolish
FT localization to the lysosome; when associated with deletion
FT of 362-G--L-366."
FT /evidence="ECO:0000269|PubMed:11150305"
FT MUTAGEN 289..298
FT /note="Missing: In delta(B) mutant; does not abolish
FT localization to the lysosome; when associated with deletion
FT of 362-G--L-366."
FT /evidence="ECO:0000269|PubMed:11150305"
FT MUTAGEN 305
FT /note="D->E: Abolished steady-state transport current."
FT /evidence="ECO:0000269|PubMed:22232659"
FT MUTAGEN 305
FT /note="D->N: Abolished transient cxurrents. Abolished
FT steady-state transport current."
FT /evidence="ECO:0000269|PubMed:22232659"
FT MUTAGEN 309
FT /note="G->C,S: Gain-of-function mutant that shows higher
FT transport of cystine."
FT /evidence="ECO:0000269|PubMed:29467429"
FT MUTAGEN 312
FT /note="S->N: Gain-of-function mutant that shows higher
FT transport of cystine."
FT /evidence="ECO:0000269|PubMed:29467429"
FT MUTAGEN 335
FT /note="K->Q: Abolished steady-state transport current.
FT Decreased midpoint potential. Impaired dielectric distance.
FT Accelerated the time course."
FT /evidence="ECO:0000269|PubMed:22232659"
FT MUTAGEN 362..366
FT /note="Missing: Strongly reduced but not abolished
FT localization to the lysosome, leading to partial relocation
FT to the cell membrane. Abolished localization to the
FT lysosome; when associated with 281-A--A-284 or deletion of
FT 280-K--N-288. Does not abolish localization to the
FT lysosome; when associated with 286-A--A-289 or deletion of
FT 289-F--S-298."
FT /evidence="ECO:0000269|PubMed:11150305,
FT ECO:0000269|PubMed:29467429"
FT MUTAGEN 362
FT /note="G->A: Does not affect localization to the lysosome."
FT /evidence="ECO:0000269|PubMed:11150305"
FT MUTAGEN 363
FT /note="Y->A: Strongly reduced but not abolished
FT localization to the lysosome, leading to partial relocation
FT to the cell membrane."
FT /evidence="ECO:0000269|PubMed:11150305,
FT ECO:0000269|PubMed:29467429"
FT MUTAGEN 364
FT /note="D->A: Does not affect localization to the lysosome."
FT /evidence="ECO:0000269|PubMed:11150305"
FT MUTAGEN 365
FT /note="Q->A: Does not affect localization to the lysosome."
FT /evidence="ECO:0000269|PubMed:11150305"
FT MUTAGEN 366
FT /note="L->A: Strongly reduced but not abolished
FT localization to the lysosome, leading to partial relocation
FT to the cell membrane."
FT /evidence="ECO:0000269|PubMed:11150305,
FT ECO:0000269|PubMed:29467429"
FT MUTAGEN O60931-2:396..400
FT /note="Missing: Abolished localization to the cell
FT membrane. Does not affect cystine transport."
FT /evidence="ECO:0000269|PubMed:27148969"
SQ SEQUENCE 367 AA; 41738 MW; 9343889CD7576908 CRC64;
MIRNWLTIFI LFPLKLVEKC ESSVSLTVPP VVKLENGSST NVSLTLRPPL NATLVITFEI
TFRSKNITIL ELPDEVVVPP GVTNSSFQVT SQNVGQLTVY LHGNHSNQTG PRIRFLVIRS
SAISIINQVI GWIYFVAWSI SFYPQVIMNW RRKSVIGLSF DFVALNLTGF VAYSVFNIGL
LWVPYIKEQF LLKYPNGVNP VNSNDVFFSL HAVVLTLIII VQCCLYERGG QRVSWPAIGF
LVLAWLFAFV TMIVAAVGVT TWLQFLFCFS YIKLAVTLVK YFPQAYMNFY YKSTEGWSIG
NVLLDFTGGS FSLLQMFLQS YNNDQWTLIF GDPTKFGLGV FSIVFDVVFF IQHFCLYRKR
PGYDQLN
