CTNS
entrez
1497
canonical
uniprot
O60931
canonical
ensembl
ENSG00000040531
resolver
ensp
ENSP00000046640
resolver
ensp
ENSP00000371294
resolver
ensp
ENSP00000461118
resolver
ensp
ENSP00000501123
resolver
ensp
ENSP00000734728
resolver
enst
ENST00000574776
resolver
enst
ENST00000673669
resolver
genesymbol
CTNS
resolver
hgnc
HGNC:2518
resolver
uniprot
A0A0S2Z3I9
resolver
uniprot
A0A0S2Z3K3
resolver
uniprot
A0A669KB82
resolver
uniprot
D3DTJ5
resolver
uniprot
I3L4A9
resolver
uniprot
Q8IZ01
resolver
uniprot
Q9UNK6
resolver
uniprot_entry
A0A0S2Z3I9_HUMAN
resolver
uniprot_entry
A0A0S2Z3K3_HUMAN
resolver
uniprot_entry
A0A669KB82_HUMAN
resolver
uniprot_entry
CTNS_HUMAN
resolver
uniprot_entry
I3L4A9_HUMAN
resolver
uniprot_sec
D3DTJ5
resolver
uniprot_sec
Q8IZ01
resolver
uniprot_sec
Q9UNK6
resolver
activity_regulation
ACTIVITY REGULATION: Switches between a lumen- and a cytosol-open conformation: pH induces conformational changes and shifts the equilibrium to facilitate the transition between the lumen- and cytosol-open conformation, thereby promoting cystine transport (PubMed:36113465). Protonation of specific aspartate residues (Asp-205, Asp-305 and Asp-346) favors the cytosol-open conformation (PubMed:36113465). {ECO:0000269|PubMed:36113465}.
uniprot
proteins
amino_acid_sequence
MIRNWLTIFILFPLKLVEKCESSVSLTVPPVVKLENGSSTNVSLTLRPPLNATLVITFEITFRSKNITILELPDEVVVPPGVTNSSFQVTSQNVGQLTVYLHGNHSNQTGPRIRFLVIRSSAISIINQVIGWIYFVAWSISFYPQVIMNWRRKSVIGLSFDFVALNLTGFVAYSVFNIGLLWVPYIKEQFLLKYPNGVNPVNSNDVFFSLHAVVLTLIIIVQCCLYERGGQRVSWPAIGFLVLAWLFAFVTMIVAAVGVTTWLQFLFCFSYIKLAVTLVKYFPQAYMNFYYKSTEGWSIGNVLLDFTGGSFSLLQMFLQSYNNDQWTLIFGDPTKFGLGVFSIVFDVVFFIQHFCLYRKRPGYDQLN
uniprot
proteins
disease_involvement
DISEASE: Cystinosis, nephropathic type (CTNS) [MIM:219800]: 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. {ECO:0000269|PubMed:10482956, ECO:0000269|PubMed:10556299, ECO:0000269|PubMed:11689434, ECO:0000269|PubMed:12204010, ECO:0000269|PubMed:12442267, ECO:0000269|PubMed:12825071, ECO:0000269|PubMed:15128704, ECO:0000269|PubMed:19852576, ECO:0000269|PubMed:21786142, ECO:0000269|PubMed:22232659, ECO:0000269|PubMed:22450360, ECO:0000269|PubMed:36113465, ECO:0000269|PubMed:9792862}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Cystinosis, adult, non-nephropathic type (CTNSANN) [MIM:219750]: 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 benign course. Patients manifest mild photophobia due to conjunctival and corneal cystine crystals. {ECO:0000269|PubMed:10625078, ECO:0000269|PubMed:15128704}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Cystinosis, late-onset juvenile or adolescent nephropathic type (CTNSJAN) [MIM:219900]: 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 is an intermediated form, manifesting 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. {ECO:0000269|PubMed:10444339, ECO:0000269|PubMed:10556299, ECO:0000269|PubMed:12442267, ECO:0000269|PubMed:15128704, ECO:0000269|PubMed:28082515, ECO:0000269|PubMed:36113465, ECO:0000269|PubMed:9792862}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Cystine/H(+) symporter that mediates export of cystine, the oxidized dimer of cysteine, from lysosomes (PubMed:11689434, PubMed:15128704, PubMed:18337546, PubMed:22232659, PubMed:29467429, PubMed:33208952, PubMed:36113465). 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 (PubMed:36113465). Also involved in small GTPase-regulated vesicle trafficking and lysosomal localization of LAMP2A, independently of cystine transporter activity (By similarity). {ECO:0000250|UniProtKB:P57757, ECO:0000269|PubMed:11689434, ECO:0000269|PubMed:15128704, ECO:0000269|PubMed:18337546, ECO:0000269|PubMed:22232659, ECO:0000269|PubMed:22649030, ECO:0000269|PubMed:29467429, ECO:0000269|PubMed:33208952, ECO:0000269|PubMed:36113465}.
uniprot
proteins
mass_dalton
41738
uniprot
proteins
mutagenesis
MUTAGEN 66; /note="N->A: Decreased glycosylation."; /evidence="ECO:0000269|PubMed:28082515"; MUTAGEN 131; /note="G->S,D: Gain-of-function mutant that shows higher transport of cystine."; /evidence="ECO:0000269|PubMed:29467429"; MUTAGEN 134; /note="Y->A,F: Nearly abolished cystine transport."; /evidence="ECO:0000269|PubMed:36113465"; MUTAGEN 137; /note="A->V: Gain-of-function mutant that shows higher transport of cystine."; /evidence="ECO:0000269|PubMed:29467429"; MUTAGEN 138; /note="W->F: Abolished cystine transport."; /evidence="ECO:0000269|PubMed:36113465"; MUTAGEN 142; /note="F->A: Abolished cystine transport."; /evidence="ECO:0000269|PubMed:36113465"; MUTAGEN 143; /note="Y->F: Slightly decreased midpoint potential. Impaired dielectric distance."; /evidence="ECO:0000269|PubMed:22232659"; MUTAGEN 145; /note="Q->A: Increased cystine uptake activity."; /evidence="ECO:0000269|PubMed:36113465"; MUTAGEN 152; /note="R->Q: Impaired dielectric distance."; /evidence="ECO:0000269|PubMed:22232659"; MUTAGEN 161; /note="D->N: Strongly reduced steady-state transport current. Slightly decreased midpoint potential."; /evidence="ECO:0000269|PubMed:22232659"; MUTAGEN 166; /note="N->A: Abolished cystine transport."; /evidence="ECO:0000269|PubMed:36113465"; MUTAGEN 170; /note="F->A: Strongly decreased cystine transport."; /evidence="ECO:0000269|PubMed:36113465"; MUTAGEN 205; /note="D->A,N: Nearly abolished cystine transport. Impaired pH-dependent conformational shift."; /evidence="ECO:0000269|PubMed:36113465"; MUTAGEN 211; /note="H->F: Accelerated the time course."; /evidence="ECO:0000269|PubMed:22232659"; MUTAGEN 270; /note="S->T: Gain-of-function mutant that shows higher transport of cystine."; /evidence="ECO:0000269|PubMed:29467429"; MUTAGEN 273; /note="K->Q: Abolished cystine transport."; /evidence="ECO:0000269|PubMed:36113465"; MUTAGEN 274; /note="L->F: Gain-of-function mutant that shows higher transport of cystine."; /evidence="ECO:0000269|PubMed:29467429"; MUTAGEN 280..288; /note="Missing: In delta(A) mutant; abolished localization to the lysosome; when associated with deletion of 362-G--L-366."; /evidence="ECO:0000269|PubMed:11150305"; MUTAGEN 281..284; /note="YFPQ->AAAA: In mu(a) mutant; abolished localization to the lysosome; when associated with deletion of 362-G--L-366."; /evidence="ECO:0000269|PubMed:11150305"; MUTAGEN 281; /note="Y->F: Strongly decreased cystine transport. Decreased midpoint potential. Accelerated the time course."; /evidence="ECO:0000269|PubMed:22232659, ECO:0000269|PubMed:36113465"; MUTAGEN 284; /note="Q->A: Increased cystine uptake activity."; /evidence="ECO:0000269|PubMed:36113465"; MUTAGEN 286..289; /note="YMNF->AAAA: In mu(b) mutant; does not abolish localization to the lysosome; when associated with deletion of 362-G--L-366."; /evidence="ECO:0000269|PubMed:11150305"; MUTAGEN 289..298; /note="Missing: In delta(B) mutant; does not abolish localization to the lysosome; when associated with deletion of 362-G--L-366."; /evidence="ECO:0000269|PubMed:11150305"; MUTAGEN 301; /note="N->A: Strongly decreased cystine transport."; /evidence="ECO:0000269|PubMed:36113465"; MUTAGEN 305; /note="D->E: Abolished steady-state transport current."; /evidence="ECO:0000269|PubMed:22232659"; MUTAGEN 305; /note="D->N: Abolished cystine transport. Abolished transient cxurrents. Abolished steady-state transport current."; /evidence="ECO:0000269|PubMed:22232659, ECO:0000269|PubMed:36113465"; MUTAGEN 309; /note="G->C,S: Gain-of-function mutant that shows higher transport of cystine."; /evidence="ECO:0000269|PubMed:29467429"; MUTAGEN 312; /note="S->N: Gain-of-function mutant that shows higher transport of cystine."; /evidence="ECO:0000269|PubMed:29467429"; MUTAGEN 319; /note="Q->A: Strongly decreased cystine transport."; /evidence="ECO:0000269|PubMed:36113465"; MUTAGEN 335; /note="K->A: Nearly abolished cystine transport."; /evidence="ECO:0000269|PubMed:36113465"; MUTAGEN 335; /note="K->Q: Abolished steady-state transport current. Decreased midpoint potential. Impaired dielectric distance. Accelerated the time course."; /evidence="ECO:0000269|PubMed:22232659"; MUTAGEN 362..366; /note="Missing: Strongly reduced but not abolished localization to the lysosome, leading to partial relocation to the cell membrane. Abolished localization to the lysosome; when associated with 281-A--A-284 or deletion of 280-K--N-288. Does not abolish localization to the lysosome; when associated with 286-A--A-289 or deletion of 289-F--S-298."; /evidence="ECO:0000269|PubMed:11150305, ECO:0000269|PubMed:29467429"; MUTAGEN 362; /note="G->A: Does not affect localization to the lysosome."; /evidence="ECO:0000269|PubMed:11150305"; MUTAGEN 363; /note="Y->A: Strongly reduced but not abolished localization to the lysosome, leading to partial relocation to the cell membrane."; /evidence="ECO:0000269|PubMed:11150305, ECO:0000269|PubMed:29467429"; MUTAGEN 364; /note="D->A: Does not affect localization to the lysosome."; /evidence="ECO:0000269|PubMed:11150305"; MUTAGEN 365; /note="Q->A: Does not affect localization to the lysosome."; /evidence="ECO:0000269|PubMed:11150305"; MUTAGEN 366; /note="L->A: Strongly reduced but not abolished localization to the lysosome, leading to partial relocation to the cell membrane."; /evidence="ECO:0000269|PubMed:11150305, ECO:0000269|PubMed:29467429"; MUTAGEN O60931-2:396..400; /note="Missing: Abolished localization to the cell membrane. Does not affect cystine transport."; /evidence="ECO:0000269|PubMed:27148969
uniprot
proteins
protein_family
Cystinosin family
uniprot
proteins
pubmed
10068513
uniprot
proteins
pubmed
10444339
uniprot
proteins
pubmed
10482956
uniprot
proteins
pubmed
10556299
uniprot
proteins
pubmed
10571941
uniprot
proteins
pubmed
10625078
uniprot
proteins
pubmed
10673275
uniprot
proteins
pubmed
11150305
uniprot
proteins
pubmed
11689434
uniprot
proteins
pubmed
12204010
uniprot
proteins
pubmed
12442267
uniprot
proteins
pubmed
12825071
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15128704
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
17897319
uniprot
proteins
pubmed
18337546
uniprot
proteins
pubmed
19852576
uniprot
proteins
pubmed
21786142
uniprot
proteins
pubmed
22232659
uniprot
proteins
pubmed
22450360
uniprot
proteins
pubmed
22544350
uniprot
proteins
pubmed
22649030
uniprot
proteins
pubmed
25753619
uniprot
proteins
pubmed
27148969
uniprot
proteins
pubmed
28082515
uniprot
proteins
pubmed
29467429
uniprot
proteins
pubmed
33208952
uniprot
proteins
pubmed
36113465
uniprot
proteins
pubmed
9537412
uniprot
proteins
pubmed
9792862
uniprot
proteins
sequence_length
367
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 1]: Lysosome membrane {ECO:0000269|PubMed:11150305, ECO:0000269|PubMed:11689434, ECO:0000269|PubMed:15128704, ECO:0000269|PubMed:17897319, ECO:0000269|PubMed:25753619, ECO:0000269|PubMed:28082515}; Multi-pass membrane protein {ECO:0000269|PubMed:36113465}. Melanosome membrane {ECO:0000269|PubMed:22649030}; Multi-pass membrane protein {ECO:0000269|PubMed:36113465}. Note=AP-3 complex is required for localization to the lysosome. {ECO:0000269|PubMed:25753619}.; SUBCELLULAR LOCATION: [Isoform 2]: Lysosome membrane {ECO:0000269|PubMed:18337546, ECO:0000269|PubMed:27148969}; Multi-pass membrane protein {ECO:0000269|PubMed:36113465}. Cell membrane {ECO:0000269|PubMed:18337546, ECO:0000269|PubMed:27148969}; Multi-pass membrane protein {ECO:0000269|PubMed:36113465}.
uniprot
proteins
transmembrane_region
TRANSMEM 126..150; /note="Helical"; /evidence="ECO:0000269|PubMed:36113465, ECO:0007744|PDB:8DKE, ECO:0007744|PDB:8DKI, ECO:0007744|PDB:8DKM, ECO:0007744|PDB:8DKW, ECO:0007744|PDB:8DKX, ECO:0007744|PDB:8DYP"; TRANSMEM 160..179; /note="Helical"; /evidence="ECO:0000269|PubMed:36113465, ECO:0007744|PDB:8DKE, ECO:0007744|PDB:8DKI, ECO:0007744|PDB:8DKM, ECO:0007744|PDB:8DKW, ECO:0007744|PDB:8DKX, ECO:0007744|PDB:8DYP"; TRANSMEM 203..225; /note="Helical"; /evidence="ECO:0000269|PubMed:36113465, ECO:0007744|PDB:8DKE, ECO:0007744|PDB:8DKI, ECO:0007744|PDB:8DKM, ECO:0007744|PDB:8DKW, ECO:0007744|PDB:8DKX, ECO:0007744|PDB:8DYP"; TRANSMEM 235..257; /note="Helical"; /evidence="ECO:0000269|PubMed:36113465, ECO:0007744|PDB:8DKE, ECO:0007744|PDB:8DKI, ECO:0007744|PDB:8DKM, ECO:0007744|PDB:8DKW, ECO:0007744|PDB:8DKX, ECO:0007744|PDB:8DYP"; TRANSMEM 264..289; /note="Helical"; /evidence="ECO:0000269|PubMed:36113465, ECO:0007744|PDB:8DKE, ECO:0007744|PDB:8DKI, ECO:0007744|PDB:8DKM, ECO:0007744|PDB:8DKW, ECO:0007744|PDB:8DKX, ECO:0007744|PDB:8DYP"; TRANSMEM 299..308; /note="Helical"; /evidence="ECO:0000269|PubMed:36113465, ECO:0007744|PDB:8DKE, ECO:0007744|PDB:8DKI, ECO:0007744|PDB:8DKM, ECO:0007744|PDB:8DKW, ECO:0007744|PDB:8DKX, ECO:0007744|PDB:8DYP"; TRANSMEM 332..354; /note="Helical"; /evidence="ECO:0000269|PubMed:36113465, ECO:0007744|PDB:8DKE, ECO:0007744|PDB:8DKI, ECO:0007744|PDB:8DKM, ECO:0007744|PDB:8DKW, ECO:0007744|PDB:8DKX, ECO:0007744|PDB:8DYP
uniprot
proteins