O60931 (CTNS_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 97.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Cystinosin | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 367 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Thought to transport cystine out of lysosomes. |
| Subcellular location | |
| Tissue specificity | Strongly expressed in pancreas, kidney (adult and fetal) and in skeletal muscle. Expressed at lower levels in placenta and heart. Weakly expressed in lung, liver and brain (adult and fetal). |
| Involvement in disease | Defects in CTNS are the cause of cystinosis nephropathic type (CTNS) [MIM:219800]. It is a form of cystinosis, a lysosomal storage disease due to defective transport of cystine across the lysosomal membrane. This results in cystine accumulation and crystallization in the cells causing widespread tissue damage. The classical nephropathic form has onset in the first year of life and is characterized by a polyuro-polydipsic syndrome, marked height-weight growth delay, generalized impaired proximal tubular reabsorptive capacity, with severe fluid-electrolyte balance alterations, renal failure, ocular symptoms and other systemic complications. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Defects in CTNS are the cause of cystinosis adult non-nephropathic type (CTNSANN) [MIM:219750]. It is a form of cystinosis, a lysosomal storage disease due to defective transport of cystine across the lysosomal membrane. This results in cystine accumulation and crystallization in the cells causing widespread tissue damage. Cystinosis adult non-nephropathic type is characterized by ocular features and a benigne course. Patients manifest mild photophobia due to conjunctival and corneal cystine crystals. Defects in CTNS are the cause of cystinosis late-onset juvenile or adolescent nephropathic type (CTNSJAN) [MIM:219900]. It is a form of cystinosis, a lysosomal storage disease due to defective transport of cystine across the lysosomal membrane. This results in cystine accumulation and crystallization in the cells causing widespread tissue damage. Late-onset juvenile or adolescent nephropathic cystinosis manifests itself first at age 10 to 12 years with proteinuria due to glomerular damage rather than with the manifestations of tubular damage that occur first in infantile cystinosis. There is no excess amino aciduria and stature is normal. Photophobia, late development of pigmentary retinopathy, and chronic headaches are features. Ref.10 Ref.12 Ref.14 |
| Sequence similarities | Belongs to the cystinosin family. Contains 2 PQ-loop domains. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Transport |
| Cellular component | Lysosome Membrane |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Disease | Disease mutation |
| Domain | Repeat Transmembrane Transmembrane helix |
| PTM | Glycoprotein |
| Technical term | Complete proteome Reference proteome |
| Gene Ontology (GO) | |
| Biological process | ATP metabolic process Inferred from mutant phenotype. Source: UniProtKB brain developmentInferred from mutant phenotype. Source: UniProtKB cognitionInferred from mutant phenotype. Source: UniProtKB glutathione metabolic processInferred from mutant phenotype. Source: UniProtKB |
| Cellular component | integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW late endosomeInferred from direct assay. Source: UniProtKB lysosomal membraneInferred from direct assay. Source: UniProtKB |
| Molecular function | L-cystine transmembrane transporter activity Inferred from mutant phenotype. Source: UniProtKB |
| Complete GO annotation... | |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: O60931-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: O60931-2) The sequence of this isoform differs from the canonical sequence as follows: 363-367: YDQLN → LQAARTGSGSRLRQDWAPSLQPKALPQTTSVSASSLKG |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 367 | 367 | Cystinosin | PRO_0000205514 | |||||
Regions | |||||||||
| Topological domain | 1 – 121 | 121 | Lumenal Potential | ||||||
| Transmembrane | 122 – 142 | 21 | Helical; Potential | ||||||
| Topological domain | 143 – 161 | 19 | Cytoplasmic Potential | ||||||
| Transmembrane | 162 – 182 | 21 | Helical; Potential | ||||||
| Topological domain | 183 – 205 | 23 | Lumenal Potential | ||||||
| Transmembrane | 206 – 226 | 21 | Helical; Potential | ||||||
| Topological domain | 227 – 237 | 11 | Cytoplasmic Potential | ||||||
| Transmembrane | 238 – 258 | 21 | Helical; Potential | ||||||
| Topological domain | 259 – 261 | 3 | Lumenal Potential | ||||||
| Transmembrane | 262 – 282 | 21 | Helical; Potential | ||||||
| Topological domain | 283 – 297 | 15 | Cytoplasmic Potential | ||||||
| Transmembrane | 298 – 318 | 21 | Helical; Potential | ||||||
| Topological domain | 319 – 335 | 17 | Lumenal Potential | ||||||
| Transmembrane | 336 – 356 | 21 | Helical; Potential | ||||||
| Topological domain | 357 – 367 | 11 | Cytoplasmic Potential | ||||||
| Domain | 123 – 189 | 67 | PQ-loop 1 | ||||||
| Domain | 263 – 328 | 66 | PQ-loop 2 | ||||||
| Motif | 362 – 366 | 5 | Lysosomal targeting motif Potential | ||||||
Amino acid modifications | |||||||||
| Glycosylation | 36 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 41 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 51 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 66 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 84 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 104 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 107 | 1 | N-linked (GlcNAc...) Potential | ||||||
Natural variations | |||||||||
| Alternative sequence | 363 – 367 | 5 | YDQLN → LQAARTGSGSRLRQDWAPSL QPKALPQTTSVSASSLKG in isoform 2. | VSP_038377 | |||||
| Natural variant | 42 | 1 | V → I. Ref.13 Corresponds to variant rs35086888 [ dbSNP | Ensembl ]. | VAR_010285 | |||||
| Natural variant | 67 – 73 | 7 | Missing in CTNSJAN. | VAR_010674 | |||||
| Natural variant | 110 | 1 | G → V in CTNS; atypical. Ref.14 | VAR_037318 | |||||
| Natural variant | 133 | 1 | I → F in CTNS. Ref.11 | VAR_010677 | |||||
| Natural variant | 139 | 1 | S → F in CTNS; atypical. Ref.13 | VAR_010678 | |||||
| Natural variant | 154 | 1 | S → SPCS in CTNSJAN. | VAR_010679 | |||||
| Natural variant | 158 | 1 | L → P in CTNS. Ref.11 | VAR_010680 | |||||
| Natural variant | 169 | 1 | G → D in CTNS. Ref.10 | VAR_010286 | |||||
| Natural variant | 177 | 1 | N → T in CTNSJAN. Ref.14 | VAR_037319 | |||||
| Natural variant | 182 | 1 | W → R in CTNS. Ref.10 | VAR_010681 | |||||
| Natural variant | 197 | 1 | G → R in CTNSANN. | VAR_010682 | |||||
| Natural variant | 200 | 1 | P → L in CTNSJAN. Ref.14 | VAR_037320 | |||||
| Natural variant | 205 | 1 | D → N in CTNS. Ref.10 | VAR_010683 | |||||
| Natural variant | 205 | 1 | Missing in CTNS. | VAR_010684 | |||||
| Natural variant | 222 | 1 | Q → R in CTNS. Ref.14 | VAR_037321 | |||||
| Natural variant | 260 | 1 | T → I. Ref.1 Ref.2 Ref.3 Ref.5 Ref.6 Ref.7 Corresponds to variant rs161400 [ dbSNP | Ensembl ]. | VAR_060371 | |||||
| Natural variant | 270 | 1 | Missing in CTNS. | VAR_010689 | |||||
| Natural variant | 280 | 1 | K → R in CTNSJAN. Ref.12 | VAR_010287 | |||||
| Natural variant | 288 | 1 | N → K in CTNS. Ref.14 | VAR_037322 | |||||
| Natural variant | 292 | 1 | K → R Found in patients with cystinosis; uncertain pathological significance. Ref.10 Corresponds to variant rs1800527 [ dbSNP | Ensembl ]. | VAR_012314 | |||||
| Natural variant | 298 | 1 | S → N in CTNS. Ref.10 | VAR_012315 | |||||
| Natural variant | 305 | 1 | D → G in CTNS. Ref.10 | VAR_010690 | |||||
| Natural variant | 305 | 1 | D → Y in CTNS. Ref.13 | VAR_010691 | |||||
| Natural variant | 308 | 1 | G → R in CTNS. Ref.10 Ref.13 | VAR_010692 | |||||
| Natural variant | 323 | 1 | N → K in CTNSJAN. Ref.12 | VAR_010288 | |||||
| Natural variant | 338 | 1 | L → P in CTNS. Ref.13 | VAR_010694 | |||||
| Natural variant | 339 | 1 | G → R in CTNS. Ref.10 Ref.13 | VAR_010695 | |||||
| Natural variant | 343 – 346 | 4 | Missing in CTNS. | VAR_010697 | |||||
| Natural variant | 346 – 349 | 4 | Missing in CTNS. | VAR_037323 | |||||
| Natural variant | 346 | 1 | D → N in CTNS; atypical. Ref.13 | VAR_010698 | |||||
| Natural variant | 349 | 1 | F → FDVEF in CTNS. | VAR_037324 | |||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis." Town M., Jean G., Cherqui S., Attard M., Forestier L., Whitmore S.A., Callen D.F., Gribouval O., Broyer M., Bates G.P., van 't Hoff W., Antignac C. Nat. Genet. 18:319-324(1998) [PubMed: 9537412] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANT ILE-260. Tissue: Kidney. |
| [2] | "The genomic region encompassing the nephropathic cystinosis gene (CTNS): complete sequencing of a 200-kb segment and discovery of a novel gene within the common cystinosis-causing deletion." Touchman J.W., Anikster Y., Dietrich N.L., Maduro V.V.B., McDowell G., Shotelersuk V., Bouffard G.G., Beckstrom-Sternberg S.M., Gahl W.A., Green E.D. Genome Res. 10:165-173(2000) [PubMed: 10673275] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ILE-260. |
| [3] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ILE-260. Tissue: Spleen. |
| [4] | "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. Nusbaum C.Nature 440:1045-1049(2006) [PubMed: 16625196] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ILE-260. |
| [6] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ILE-260. Tissue: Testis. |
| [7] | "Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS)." Anikster Y., Lucero C., Touchman J.W., Huizing M., McDowell G., Shotelersuk V., Green E.D., Gahl W.A. Mol. Genet. Metab. 66:111-116(1999) [PubMed: 10068513] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 228-367, VARIANT ILE-260. |
| [8] | "CTNS mutations in patients with cystinosis." Anikster Y., Shotelersuk V., Gahl W.A. Hum. Mutat. 14:454-458(1999) [PubMed: 10571941] [Abstract] Cited for: REVIEW ON VARIANTS CYSTINOSIS. |
| [9] | "Integral and associated lysosomal membrane proteins." Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H., Elsaesser H.-P., Mann M., Hasilik A. Traffic 8:1676-1686(2007) [PubMed: 17897319] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Tissue: Placenta. |
| [10] | "CTNS mutations in an American-based population of cystinosis patients." Shotelersuk V., Larson D., Anikster Y., McDowell G., Lemons R., Bernardini I., Guo J., Thoene J., Gahl W.A. Am. J. Hum. Genet. 63:1352-1362(1998) [PubMed: 9792862] [Abstract] Cited for: VARIANTS CTNS ASP-169; ARG-182; ASN-205; ASP-205 DEL; ASN-298; GLY-305; ARG-308 AND ARG-339, VARIANT CTNSJAN 67-ILE--PRO-73 DEL, VARIANT ARG-292. |
| [11] | "Molecular analysis of cystinosis: probable Irish origin of the most common French Canadian mutation." McGowan-Jordan J., Stoddard K., Podolsky L., Orrbine E., McLaine P., Town M., Goodyer P., MacKenzie A., Heick H. Eur. J. Hum. Genet. 7:671-678(1999) [PubMed: 10482956] [Abstract] Cited for: VARIANTS CTNS PHE-133 AND PRO-158. |
| [12] | "Mutations of CTNS causing intermediate cystinosis." Thoene J., Lemons R., Anikster Y., Mullet J., Paelicke K., Lucero C., Gahl W.A., Schneider J., Shu S.G., Campbell H.T. Mol. Genet. Metab. 67:283-293(1999) [PubMed: 10444339] [Abstract] Cited for: VARIANTS CTNSJAN ARG-280 AND LYS-323. |
| [13] | "Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin." Attard M., Jean G., Forestier L., Cherqui S., van 't Hoff W., Broyer M., Antignac C., Town M. Hum. Mol. Genet. 8:2507-2514(1999) [PubMed: 10556299] [Abstract] Cited for: VARIANTS CTNS PHE-139; SER-270 DEL; TYR-305; ARG-308; PRO-338; ARG-339 AND ASN-346, VARIANT ILE-42. |
| [14] | "Identification of 14 novel CTNS mutations and characterization of seven splice site mutations associated with cystinosis." Kalatzis V., Cohen-Solal L., Cordier B., Frishberg Y., Kemper M., Nuutinen E.M., Legrand E., Cochat P., Antignac C. Hum. Mutat. 20:439-446(2002) [PubMed: 12442267] [Abstract] Cited for: VARIANTS CTNS VAL-110; ARG-222; LYS-288; ASP-346--349-PHE DEL AND ASP-VAL-GLU-PHE-349 INS, VARIANTS CTNSJAN THR-177 AND LEU-200. |
| + | Additional computationally mapped references. |
Web resources
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | Y15924 Y15933 Genomic DNA. Translation: CAA75882.1.AJ222967 mRNA. Translation: CAA11021.1. AF168787 Genomic DNA. Translation: AAF43102.1. AK292019 mRNA. Translation: BAF84708.1. AC027796 Genomic DNA. No translation available. AC132942 Genomic DNA. No translation available. CH471108 Genomic DNA. Translation: EAW90495.1. CH471108 Genomic DNA. Translation: EAW90494.1. CH471108 Genomic DNA. Translation: EAW90496.1. BC032850 mRNA. Translation: AAH32850.1. AF112442 Genomic DNA. Translation: AAD45630.1. |
| IPI | IPI00412430. IPI00644266. |
| RefSeq | NP_001026851.2. NM_001031681.2. NP_004928.2. NM_004937.2. |
| UniGene | Hs.187667. |
3D structure databases | |
| ProteinModelPortal | O60931. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | O60931. |
Protein family/group databases | |
| TCDB | 2.A.43.1.1. lysosomal cystine transporter (LCT) family. |
Proteomic databases | |
| PRIDE | O60931. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000046640; ENSP00000046640; ENSG00000040531. |
| GeneID | 1497. |
| KEGG | hsa:1497. |
Organism-specific databases | |
| CTD | 1497. |
| GeneCards | GC17P003486. |
| H-InvDB | HIX0027321. |
| HGNC | HGNC:2518. CTNS. |
| MIM | 219750. phenotype. 219800. phenotype. 219900. phenotype. 606272. gene. |
| neXtProt | NX_O60931. |
| Orphanet | 213. Cystinosis. |
| PharmGKB | PA27019. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG15325. |
| HOVERGEN | HBG003083. |
| OMA | FQVTSQN. |
| OrthoDB | EOG4QVCCB. |
| PhylomeDB | O60931. |
Gene expression databases | |
| ArrayExpress | O60931. |
| Bgee | O60931. |
| CleanEx | HS_CTNS. |
| Genevestigator | O60931. |
| GermOnline | ENSG00000040531. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR006603. CTNS. IPR005282. LC_transporter. [Graphical view] |
| KO | K12386. |
| SMART | SM00679. CTNS. 2 hits. [Graphical view] |
| TIGRFAMs | TIGR00951. 2A43. 1 hit. |
| ProtoNet | Search... |
Other | |
| DrugBank | DB00138. L-Cystine. |
| SOURCE | Search... |
Entry information
| Entry name | CTNS_HUMAN | ||||||||
| Accession | Primary (citable) accession number: O60931 Secondary accession number(s): D3DTJ5, Q8IZ01, Q9UNK6 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 17 Human chromosome 17: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with